Evidence for participation of cytochrome b5 in microsomal delta-6 desaturation of fatty acids. The delta-6 desaturation of linoleic acid to gamma-linolenic acid and oleic acid to 6,9-octadecadienoic acid by rat liver microsomes was investigated. Using a specific antibody prepared against purified rat liver cytochrome b5, we demonstrated that cytochrome b5 participated in delta-6 desaturation of both fatty acids. The reaction products were identified as their methyl ester derivatives by argentation thin-layer chromatography, gas-liquid chromatography, and reductive ozonolysis followed by gas-liquid chromatography.


On the reactivities of the tryptophan residues of human alpha-lactalbumin to 2-hydroxy-5-nitrobenzyl bromide. The reaction of human alpha-lactalbumin with the tryptophan reagent 2-hydroxy-5-nitrobenzyl bromide has been studied. This protein has 3 tryptophan residues (Trp-60, Trp-104 and Trp-118) all of which are accessible to the reagent at pH 2.7 or 7. Trp-60 of human alpha-lactalbumin is much more reactive than Trp-60 of bovine alpha-lactalbumin (Barman, T. E. (1972) Biochim. Biophys. Acta 257, 297-313). As with bovine alpha-lactalbumin, at pH 2.7, 2-hydroxy-5-nitrobenzyl bromide is specific for tryptophan but at pH 7 His-32 also reacts. When treated with the tryptophan reagent, both alpha-lactalbumins lose their specifier protein activities in the lactose synthase (UDPgalactose:D-glucose 4-beta-galactosyltransferase, EC 2.4.1.22) reaction.


Effects of amidination and chemical cross-linking on human factor VIII (antihemophilic factor). The bifunctional reagent dimethyl suberimidate, reacting with primary amino groups of proteins, was used to cross-link highly purified human factor VIII. Reaction products were reduced with beta-mercaptoethanol or treated with Rhizopus arrhizus triglyceride lipase. The proportions of the dissociated subunits and their oligomers were calculated from the relative staining intensities of individual bands following polyacrylamide electrophoresis in the presence of sodium dodecyl sulfate. Low concentrations of dimethyl suberimidate (up to 0.5 mM) produced covalently linked dimers which retained full functional (coagulant and von Willebrand factor) activities. Treatment with increasing concentrations of dimethyl suberimidate resulted in an almost simultaneous appearance of both trimeric and tetrameric species, suggesting the existence of specific intra-dimer contacts. A parallel decrease of functional activities was observed at higher concentrations of dimethyl suberimidate. A monofunctional reagent (ethyl acetimidate), reacting similarly with primary amino groups, amidinated factor VIII at rates similar to dimethyl suberimidate. Up to 40% amidinated factor VIII retained full biological activities. We conclude that the most reactive lysine residues are not involved in the active sites responsible for either coagulant or von Willebrand activity.


An abnormal human IgA1 half-molecule.

An abnormal human IgA1 half-molecule. An IgA1 half-molecule, which is composed of a deleted alpha1 chain linked with a disulfide bond to an intact kappa chain, was detected in a patient (Cha). The molecular weights of the paraprotein and the isolated alpha1 chain were estimated to be 75 000 and 53 000, respectively. Identification of tyrosine as the C-terminal amino acid and the presence of idiotypic determinants in the abnormal alpha1 chain indicated that the molecule would have an intact N-terminal variable region and a C-terminal region. Furthermore, no cleavage of the abnormal protein into Fab and Fc by proteolytic enzyme isolated from Neisseria gonorrhoeae suggested the absence of a "hinge" region in the abnormal alpha1 chain.


The extraction and partial characterization of proteins released by decalcification from calcified human aortic plaques. Tissue from severely atherosclerotic human aortas was divided into heavily calcified (plaque) and less calcified (non-plaque) areas. After defatting and thorough extraction with neutral salt solutions, further proteinaceous material was released from plaque than non-plaque areas. Although organic phosphorous was associated with the EDTA-solubilized protein from both plaque and non-plaque areas, the phosphorous to protein ratio of extracts from plaque areas was 2 to 3 times that from non-plaque areas. Analysis of the major protein component of the extract of plaque areas indicated an acidic glyco-protein which appeared to be associated with an organic phosphorous moiety as well as cholesterol and cholesterol esters.


The origin of citrulline-containing proteins in the hair follicle and the chemical nature of trichohyalin, an intracellular precursor. The present studies have demonstrated that the medulla and inner root sheath cells develop within their cytoplasm a protein that is unique in composition and is present in the trichohyalin granules. The protein is rich in arginine residues, some of which undergo a side-chain conversion in situ into citrulline residues. An unusual Ca2+-dependent enzyme activity distinguishable from cross-linking transamidase has been detected in the hair follicle and will act in vitro on trichohyalin protein as the natural substrate. The conversion in vivo must occur during the time that the medullary and inner root sheath cells move up the follicle and their cytoplasm fills with cross-linked protein containing citrulline. The function of citrulline in these proteins is not understood but its formation is a major process during hair growth.


Rat alpha1-acid glycoprotein. Purification and immunological estimation of its serum concentration. A rapid method is described for the preparation of serum alpha1-acid glycoprotein from rats with inflammation induced with turpentine oil injection. The protein obtained by two purification steps, batchwise adsorption with DEAE-cellulose followed by chromatography on CM-cellulose, was proved to be native alpha1-acid glycoprotein in a high degree of purity by electrophoretical, immunological, ultracentrifugal and carbohydrate analysis. The monospecific and potent antiserum to this protein was prepared by immunizing rabbits with the desialyzed material emulsified with Freund's incomplete adjuvant. Using purified alpha1-acid glycoprotein and its specific antiserum, the concentration of alpha1-acid glycoprotein in rat serum was determined by single radial immunodiffusion. Abnormally high levels of its concentration (5-6 times higher than the control) were observed in inflammatory and tumor bearing rats.


Biosynthesis of N-methyl-L-glucosamine from D-glucose by Streptomyces griseus. Biosynthesis of N-methyl-L-glucosamine moiety of streptomycin from D-glucose by Streptomyces griseus was studied. A mixture of D-[1-(14) C] glucose and D-[6(-3)H]glucose was given to the culture of S. griseus. The 3H/14C ratio found in N-methyl-L-glucosamine further supports a mechanism that the conversion of D-glucose to L-hexose is carried out without scission of carbon skeleton. When D-[1-14C]glucose and D-[3-3H]glucose were used, the fall of 3H/14C ratio in N-metyl-L-glucosamine showed that the hydrogen atom at C-3 plays a rôle in such a transformation.


[Effects of mutations in Bacillus subtilis genome decreasing the protease activity on the formation of subtilisin molecular forms]. Multiple molecular forms of subtilisin--extracellular serine protease produced by the wild strain Bac. subtilis A-50 and its mutant strains with the protease activity decreased two-fold and more were studied. Six molecular forms of subtilisin were found on the whole when 33 mutant strains have been investigated under the experimental conditions. It is essential that both the wild and each of mutant strains under study produced not more than three out of these six forms. Three molecular forms of subtilisin from the mutant strains are similar to those found in the wild strain A-50, and have the molecular weight, of 27 000-30 000. Three other forms of subtilisin were revealed only in the mutant strains, and had the molecular weight of about 20 000. Apparently there is only one structural gene for subtilisin in Bac. subtilis genome. The appearence of multiple molecular forms of subtilisin may be due to the post-translational modifications (limited proteolysis) of the initial type of enzyme, i.e. pre-subtilisin. Probably, that certain mulations not affecting the structural gene can significantly change the expression of such gene by varying of the degree of product modifications.


[Large-scale purification, crystallization and some physicochemical properties of extracellular guanyl-RNases C2 and Pch1]. The purification of RNase C2 from 76.5 1 of Asp. clavatus cultural fluid and RNase Pch1 from 160 1 of Pen. chrysogenum 152 A cultural fluid was described. 1150-fold purification of RNase C2 was attained by precipitation with ammonium sulfate, ion-exchange chromatography and rechromatography on DEAE-cellulose, gel chromatography on Sephadex G-75, and crystallization from diluted acidic buffer. During the preparation of RNase Pch1 additional chromatography on CM-cellulose was used before crystallization, the purification being 2220-fold. It was obtained 600 mg RNase C2 and 900 mg RNase Pch1. Some physico-chemical properties of crystalline RNases were studied.


[Glutaraldehyde and glyoxal fixation of ribonucleoproteins for their analysis by cesium chloride equilibrium gradient centrifugation]. Conditions for fixation of different RNP (ribosomes, poliribosomes, informosomes) by glutaraldehyde and glyoxal for their subsequent analysis in CsCl density-gradient has been developed. Higher dialdehyde concentration and longer incubation time should be used for fixation of ribosomes and polyribosomes than for that of informosomes. For the fixation of all RNP studied their incubation with 0.01 M (0.1%) glutaraldehyde for several minutes is sufficient. Much higher concentration of the fixating agent (about 0.2-0.5 M i. e. 1-3%) and more prolonged time of incubation (in order of several 10 hours) are needed for the fixation of the RNP in the case of glyoxal. Conditions for selective aldehyde fixation of informosomes in the presence of ribosomes and polyribosomes has been developed.


[Selective permeability of bacterial membranes for monovalent thallium ions]. Transport of monovalent thallium ions in bacterial cells was studied. An energy-dependent transport of T1+ against electrochemical gradient into the cells of S. faecalis and Micrococcus lysodeikticus, according to the Michaelis-Menten kinetics was observed. T1+, being a K+ analog, is involved into active K+ transport. Unlike K+, T1+ readily penetrates bacterial membranes, reaching the level of stationary distribution between the cells and the medium. This permits to use T1+ as a penetrating cation to study the mechanism of potassium transport in bacteria without the use of ionophores, which can destroy the integrity of cell membranes.


[Radioimmunoassay for the determination of angiotensin II and its fragments]. A radioimmunoassay procedure for the determination of angiotensin and its fragments: C-terminal hexapeptide and middle tetrapeptide has been developed. The sensitivity of the method reaches up to 5 ng/ml. The accuracy calculated from the standard deviation, for angiotensin and of its fragments presents the average +/- 1,5%; reproducibility (n = 10) is +/- 0,51% for angiotensin, +/- 2,12% for C-terminal hexapeptide and +/- 6,93% for the middle tetrapeptide. Using the Ouchterlony test with the cross-reactions showed that antibodies elicited to angiotensin interact with its fragments--middle tetrapeptide and C-terminal hexapeptide.


Histological observations on thymic development in fetal and newborn mammals subject to intrauterine growth retardation. Fetal growth retardation resulting from maternal dietary protein deprivation (rats) or Coxsackie virus B3 infection in mid-pregnancy (mice) was associated with delayed thymic development. Histological examination revealed that less darkly staining small lymphocytes were present and that the thymus was not well organised into cortex and medulla as seen in the normal-weight fetuses. In preterm or neonatal piglets, the histological pattern of the thymus did not vary appreciably according to the body weight of the fetus. Hassall's corpuscles were present and the tissues were well organised into cortex and medulla regions. Although fetal growth retardation in rats and mice leads to an apparent delay in the differentiation of the thymus, functional studies are necessary to understand the immunological significance of this finding.


Alterations in the rate of fetal and placental development as a consequence of early maternal protein/calorie restriction. The in utero growth rates have been determined for the body, brain, and the placenta in the rat. The accumulation of cell number (DNA content) and protein content in the cerebrum and the placenta were investigated during normal development. When rats were exposed to a severe reduction in protein/calorie intake during the first 10 days of pregnancy and the fetal growth rates were compared to those of the normal control animals, highly significant differences were observed. Pregnant rats, which were restricted in their protein/calorie intake during the early part of pregnancy, significantly prolonged the gestation time. When this increase of in utero time is taken into consideration and the offspring are compared at the time of natural birth, the data presented demonstrate the possibility of in utero catch up growth. The variations, in fetal development within the same litter and across litters, demonstrate a considerable plasticity during normal development in utero.


Preclinical toxicological study of phosphonoacetic acid: determination in blood by selected ion monitoring. Confirmed observations of the inhibition of oncogenic viruses by phosphonoacetic acid led to preclinical trials in animal model systems. Circulating phosphonoacetic acid was detected in the blood of mouse, rabbit and monkey after oral or subcutaneous administration of the drug. Phosphonoacetic acid is quantified in blood, after removing proteins and lipids, as the trimethylsilylated derivative, by monitoring the intensity of the protonated molecular ion and also that of phosphonopropionic acid (internal standard) using chemical ionization mass spectrometry combined with gas chromatography. The detection limit is 20 ng ml-1 when 0.2 ml serum is analyzed. A dosage of 230 mg kg-1 day-1 by continuous infusion is proposed for therapeutic trials in monkeys. This dose is well tolerated and results in slowly increasing blood levels of phosphonoacetic acid which reach a maximum of approximately 50 microgram ml-1 in a four day infusion, and decrease to 2 microgram ml-1 24 h after termination.


Gas chromatography mass spectrometry assay for ketamine and its metabolites in plasma. A highly sensitive and specific method for quantitation of ketamine and two of its metabolites found in monkey, dog and human plasma was developed using a gas chromatography selected ion monitoring assay operated in both electron impact and chemical ionization modes. This technique yields excellent precision, reproducibility and accuracy. From 1 ng to 3 microgram of ketamine or its metabolites in 1 ml of plasma can be detected. The technique of electron capture gas chromatography is compared. All three assays were found to be quite useful but the gas chromatography mass spectrometry techniques were more specific.


[Effect of antioxidants and complexons on mitochondrial swelling induced by thyroxine]. The rate of thyroxin-induced swelling of rat liver mitochondria depended but little on the cation compositions of the medium (KCl, NaCl or choline chloride), this indicating that the enhancement of mitochondrial membrane permeability for cations in the presence of thyroxin was of negligible selectivity. The antioxidants alpha-tocopherol and beta-ionol in concentrations completely inhibiting the lipid perioxidation failed to affect the thyroxin-induced mitochondrial swelling; hence the latter could not be attributed to the lipoperoxidation. The kinetics of the swelling and the fact of its inhibition by EGTA imply the necessity of calcium ions in the activation of the process and make possible a postulation that the thyroxin-based mitochondrial swelling was based on the process of activation of the membrane phospholipase in these organellae.


[Character of Auerbach's plexus receptors in the stomach and small intestine]. The motility of the stomach and jejunum in 8 fed dogs with the intact vagus nerves was registered by the balloon method. Subcutaneous injection of benzohexonium (0.125--0.5 ml of 2.5% soltuion) and atropine (0.12--0.25 ml of 0.1% solution) or metacine (0.125--0.25 ml of 0.1% solution) to 6 dogs proved to induce a transition from digestive motility to the periodic form after a transient depression of the digestive motility. The same effect followed injection of 0.5--1.0 ml of 0.1% atropine only in 2 dogs and 1.0 ml of 0.1% metacine in 1 dog. Since retention of periodic motility following food consumption was inherent for vagotomized dogs, a conclusion was drawn that the experimental dog had "pharmacologic vagotomy". It was suggested that the muscarine receptors on the Auerbach's plexus cells exceeded the nicotine receptor in number.


[Transgenosis with participation of plasmid RP1; indications of the presence of a "composit plasmid" in an interspecies hybrid of Escherichia coli]. One of the transconjugants (1-7) obtained by the authors earlier in the conjugation of Escherichia coli J-62 with Pseudomonas aeruginosa 1822, besides the plasmic RP1 has acquired the ability to grow without proline and tryptophan. The detailed analysis has shown that in the conjugation of the transconjugant 1-7 with different strains of E. coli the plasmic RP1 and chromosomal genes were transmitted together, but in transduction--by means of bacteriophage P1, independently of each other. The fertility was found only in the transductants carrying the plasmid RP1. This suggests that in the intergeneric conjugations the transmission of chromosomal genes may occur without any firm link with the plasmid (as in the case of "aggregated plasmids"). In E. coli cells these chromosomal fragments of Ps. aeruginosa apparently formed small nontransmissible replicons.


Reactivity of isolated human cerebral arteries to biogenic amines. Serotonin (5-HT), histamine, norepinephrine, methoxamine and isoproterenol caused dose-dependent contraction of human cerebral arteries. The potency of 5-HT was greater among test agents in the basilar arteries, whereas it was equivalent to that of norepinephrine in human anterior, middle and posterior cerebral arteries. Acetylcholine and carbachol (10(-9)-10(-5) M) caused a negligible response in human cerebral arteries. Contractile response to 5-HT was greater in the distal rather than middle portion of the human basilar arteries while this order was reversed in the response to norepinephrine. Tyramine (10(-4) M) caused tonic contraction and nicotine (10(-4) M) and electrical transmural stimulation produced phasic contraction of arteries which were antagonized by adrenergic blocking agents. Adenine nucleotides failed to cause relaxation and only high concentration of adenosine caused a minute relaxation. However, papaverine and nitroglycerin caused marked relaxation. These results suggest that adrenergic mechanism may play a role in the regulation of vascular tone in human cerebral arteries.


The role of total skin irradiation with electrons in the management of mycosis fungoides. The study presents a group of 176 patients with biopsy proven mycosis fungoides treated with total skin irradiation with electrons. The treatment resulted in a complete disappearance of all cutaneous lesions in 117/176 (66 percent) of the patients. The rate of complete remission was dose-dependent and was inversely dependent on the extent of the disease. Nineteen patients have been continuously free of any evidence of mycosis fungoides 4-14 years following a single course of treatment and may be considered as cured. Most of the patients presenting with significant peripheral lymphadenopathy (Stage II) eventually relapsed with cutaneous lesions and 37 percent of these patients developed extra-cutaneous dissemination. The prognosis of patients with extracutaneous involvement was poor and no patients in this series survived for more than three years after the histological diagnosis of extractaneous dissemination. The role of total skin irradiation with electrons in the management of each stage of the disease, given either alone or in combination with other treatment modalities, is discussed.


Mycosis fungoides. Electron beam therapy. The most effective treatment of late mycosis fungoides is total skin electron beam therapy. The beam at the Hammersmith Hospital in London has been adapted to treat these patients. Patients with advanced disease who have failed more conservative methods of treatment are irradiated. The electron beam is modified by the use of carbon and copper scatterers to produce an 80 percent depth dose at 5.5, 8 and 11.5 millimeters below the skin surface. The dose achieved in most patients is between 1500 rads and 2600 rads given in 10 to 13 treatments over 5-7 weeks. Recently the higher dose range has been employed and lithium flouride studies have shown that giving these doses from each of 4 fields, the dose achieved on the skin is approximately twice the given dose. The management of patients and the effects of treatment are discussed.


Development and significance of antibodies to salmon calcitonin in patients with Paget's disease on long-term treatment. Sixteen consecutive patients in one unit were studied during long-term treatment of Paget's disease of bone with salmon calcitonin. Eleven patients developed detectable antibody titres at some time during treatment. In one patient with a high antibody titre evidence of resistance to treatment emerged two years after the development of antibodies, but no other patient showed evidence of resistance. The clinical and biochemical response could be maintained in the absence of an acute calcium-lowering effect of calcitonin. Although antibodies often develop during treatment with heterologous calcitonin, they are only rarely the cause of clinical resistance.


Limbic and prefrontal contributions to somesthetic learning in monkeys. Monkeys with forebrain commissurotomies and either lateral temporal, medial temporal, dorsal prefrontal, or ventral prefrontal removals from the right hemisphere were compared with control animals in learning tactual discriminations and reversal with the left hand. The lateral temporal removal yielded no effect, confirming the modality-specific roles of this sector in audition (superior temporal gyrus) and vision (inferior temporal gyrus). The dorsal prefrontal removed yielded a deficit in discrimination learning, possibly as a result of the contralateral sensory neglect or the spatial disorder produced by this lesion. Each of the two remaining lesions, medial temporal and ventral prefrontal, yielded deficits in both discrimination learning and reversal; and the effects of combined removal of these two limbic sectors appeared to be additive. Taken together with earlier findings in vision and audition, the results indicate that the two limbic sectors contribute to learning in all sensory modalities, and that they do so through cortico-cortical interaction with the sensory systems.


Thalamic projections of the hippocampal formation: evidence for an alternate pathway involving the internal capsule. Experiments were performed using [3H]leucine radioautography and horseradish peroxidase histochemistry to determine the origin and distribution of the projection from the hippocampal formation to the thalamus in the rat. The results confirm recent findings that postcommissural fornix fibers which project to the anterior thalamus arise exclusively from the subicular cortex and not from hippocampal pyramidal cells. A second significant feature of this pathway is that it arises from cells situated in the deepest layer of subicular cortex at dorsal and posterior levels of the hippocampal formation. Thirdly, one component of this projection involves the internal capsule instead of the fornix. Fibers which pass through this fiber bundle arise from the lateral portion of the subicular complex adjacent to field CA1 of the hippocampus (i.e., prosubiculum) and terminate bilaterally throughout the anteromedial thalamic nucleus. In contrast, fibers from the region of subicular cortex adjacent to the retrosplenial cortex (i.e., presubiculum) pass through the postcommissural fornix and terminate in the ventral portion of the anteroventral thalamic nucleus. Fibers from central portions of the subicular complex (i.e., subiculum) project through both the internal capsule and postcommisural fornix and terminate in the anteromedial and adjacent ventral portion of the anteroventral thalamic nuclei. Fibers which project to the dorsal portion of the anteroventral thalamic nucleus arise from adjacent portions of retrosplenial cortex and project through the internal capsule.


Decrease in neostriatal blood flow after D-amphetamine administration or electrical stimulation of the substantia nigra. Local blood flow was measured in the caudate nuclei and, in some cases, other areas of rat and monkey brain by the hydrogen clearance technique. Resting values for caudate blood flow in the rat were similar to those reported elsewhere, i.e., 69 +/- 4 ml/min/100 g in the caudate. Administering D-amphetamine sulfate (0.5 mg/kg, i.p.) to rats reduced caudate flow by a maximum of about 33% after 30 min; this effect could be blocked by pretreatment with haloperidol (5.0 mg/kg, i.p.), a drug that blocks dopamine receptors. D-Amphetamine sulfate (1.5 mg/kg) also reduced caudate but not cortical blood flow in unanesthetized monkeys. Electrical stimulation of the pars compacta of the substantia nigra reduced ipsilateral caudate flow by about 25% without affecting flow in the contralateral caudate. This effect varied with the frequency and intensity of stimulation. These studies suggest that the intraparenchymal release of brain dopamine may modify intraparenchymal (local) blood flow.


Lacunar cells of nodular sclerosing Hodgkin's disease: an ultrastructural and immunohistologic study. Tissues from 22 cases of nodular sclerosing Hodgkin's disease were studied by light and electron microscopy in conjunction with immunohistologic and cytochemical staining. The presence of lipid in the cytoplasm of lacunar cells suggested that this was responsible for the distinctive "lacunar" appearance of the cells. Marked morphologic similarities between "blast cells" resulting from mitogen stimulation of lymphocytes in vi-ro, immunoblasts seen in reactive lymphoid tissues, and mononuclear "Hodgkin's" cells in Hodgkin's disease suggested that all three cell types may result from lymphocyte transformation. It also seemed apparent that there was a developmental sequence from lymphocyte to transformed lymphocyte to the abnormal mononuclear Hodgkin's cell, with further progression, through increasing size and nuclear lobulation, to the lacunar cell or, alternatively, to the diagnostic Reed-Sternberg cell. This proposed sequence was supported by immunoperoxidase studies in which cytoplasmic immunoglobulin was demonstrated in mononuclear Hodgkin's cells, lacunar cells and Reed-Sternberg cells. The proposed relationship between these cells was also supported by the findings of both kappa and lambda chains in the same cells, a pattern not seen in reactive transformed lymphocytes.


Acute myelomonocytic leukemia in a patient with macroglobulinemia and malignant lymphoma. Acute myelomonocytic leukemia occurred in a 69-year-old man with malignant lymphoma and macroglobulinemia. Fluorescent staining demonstrated the macroglobulin in plasma and leukemic cells. Plasma cells seemed to be producing paraproteins, while leukemic cells appeared to be engulfing them as seen with transmission electron microscopy. The sequence of events ruled out the possibility that myelomonocytic leukemia developed following the use of cytotoxic drugs. The case presented in this report is a rare example of malignant lymphoma, macroglobulinemia, and acute myelomonocytic leukemia occurring in the same patient.


Malignant tumors of the testis: analysis of treatment results and sites and causes of failure. A total of 150 patients with germinal testicular neoplasms treated at the University of California, San Francisco, were reviewed. The 5-year actuarial survival rate was 95% for 57 patients with seminoma and 56% for 75 patients with carcinoma. Treatment modalities were compared with respect to sites and causes of failure and complications. The most common sites of failure in the carcinoma patients were lung, and supraclavicular or mediastinal lymph nodes. Scrotal orchiectomy, elevated gonadotropins, elements of choriocarcinoma, and bulky abdominal disease were all correlated with high treatment failure rate.


Adenocarcinoma of the pancreas associated with neurofibromatosis. A case of adenocarcinoma of the pancreas in a 27-year-old woman with neurofibromatosis (von Recklinghausen's disease) is presented.


1,5-anhydro-2-deoxy-3-O-(2-deoxy-beta-D-arabino-hexopyranosyl)-D-arabino-hex-1-enitol, the by-product in the enzymic hydration of D-glucal by beta-D-glucosidase from emulsin. The by-product (3) in the hydration of D-glucal (1) catalyzed by emulsin beta-D-glucosidase has been identified as 1,5-anhydro-2-deoxy-3-O-(2-deoxy-beta-D-arabino-hexopyranosyl)-D-arabino-hex-1-enitol. Two models for the formation of 3 are discussed, involving transfer of a 2-deoxy-D-arabino-hexopyranosyl cation to HO-3 of D-glucal (glycon transfer) and transfer of an allylic D-pseudoglucal cation to HO-1 of 2-deoxy-D-arabino-hexopyranose (aglycan transfer). The enzymic production of 3 is highly regiospecific, which lends support to the second model and implies the presence of a specific binding-site for the aglycon moiety.


The stereochemistry of the addition of glycerol to D-galactal, catalyzed by beta-D-galactosidase. On incubation with beta-D-galactosidase, D-galactal-2-d (1) plus glycerol yielded 1-deoxyglycerol-1-yl 2-deoxy-beta-D-lyxo-hexopyranoside-2(S)-d. By 1H-n.m.r. analysis, it was shown that the hydrogen atom introduced on C-2 is trans-related to the aglycon moiety. In contrast to this stereospecific, enzyme-catalyzed addition, the reaction of phenol with peracetylated 1, catalyzed by p-toluenesulfonic acid, which yields phenyl 3,4,6-tri-O-acetyl-2-deoxy-alpha-D-lyxo-hexopyranoside-2-d, was shown to entail both a trans and a cis addition.


Transcription at two heat shock loci in Drosophila. Transcription at two heat shock loci in Drosophila melanogaster, in subdivisions 87A and 57C, was investigated by hybridization in situ with 3H-labeled messenger, nuclear RNA and whole cell RNA from cells cultured at elevated temperature. What appears to be the same 9 x 10(5) dalton heat shock message hybridizes at both sites. At 87a, little additional hybridization is obtained with nuclear or whole cell RNA. In contrast, at 87C the saturation level of hybridization by nuclear and whole cell RNA is much higher than that obtained with the message alone. This evidence for extensive hybridization at 87C but not at 87A by RNA distinct from the message is confirmed by the finding that excess nonradioactive message competes away most of the hybridization by 3H-labeled nuclear and whole cell RNA at the latter locus but not at the former. The noncompetable RNA migrates on an electrophoretic gel as a heterogeneous population of molecules, extending to sizes both larger and smaller than the message. These and other observations lead to the conclusion that a 87A transcription includes little more than sequences complementary to the 9 x 10(5) dalton message, while at 87C, there are sequences complementary to the same message and extensive additional sequences complementary to other species of RNA.


Cloned MPC 11 myeloma cells express two kappa genes: a gene for a complete light chain and a gene for a constant region polypeptide. Cloned MPC 11 mouse plasmacytoma cells synthesize a complete kappa light chain and also a kappa light chain constant region fragment. Partial amino terminal sequences of the in vitro forms of these two proteins have been determined. Both in vitro products contain typical light chain leaders; leaders are defined as the amino terminal sequences present on in vitro products but absent from the in vivo products found in living cells. The in vitro form of the MPC 11 complete light chain contains a leader sequence plus variable and constant region sequences. The in vitro form of the MPC 11 light chain constant region fragment contains a different leader sequence attached directly to a complete constant ragion sequence and has no variable region sequences. Thus the MPC 11 light chain fragment is not a degradation product of the MPC 11 complete light chain (or of any other complete light chain) and must be coded by a separate gene. The results reveal two unusual features of MPC 11 cells: first, expression of a unique variant light chain gene coding the light chain constant region fragment, and second, expression of two different kappa light chain genes (coding the complete light chain and the variant constant region fragment) in a single cell. In addition, evidence is provided that the in vitro forms of kappa light chains, three of which are presented here for the first time, include a minimum of three partially homologous but quite different leader sequences.


The mitochondrial DNA of Drosophila melanogaster exists in two distinct and stable superhelical forms. We have studied the structure and replication of mitochondrial DNA from Drosophila melanogaster embryos, larvae, adult flies and two established tissue culture lines. The most striking observation is that the organism maintains at least two stable, distinct closed circular forms of mitochondrial DNA throughout development of the early embryo and in the adult fly. The major closed circular monomeric form comprises approximately 75% of the population and has a normal number of superhelical turns. In contrast, closed circular mitochondrial DNA isolated from Drosophila tissue culture cells is comprised almost entirely of molecules with the low superhelix density. We have been unable to detect the D loop form of mitochondrial DNA present in other eucaryotic systems, and find by electron microscope and pulse-chase labeling techniques that the time required to replicate Drosophila mitochondrial DNA is very short (less than 15 min) compared to the mouse L cell system (greater than 1 hr). We conclude that Drosophila mitochondrial DNA utilizes a replication mechanism different from that of other higher eucaryotes. We postulate that the maintenance of markedly different topological forms of mitochondrial DNA is most probably related to different demands for replication and transcription of the genome in these sources.


Aflatoxin B1, a selective inhibitor of DNA synthesis in mammalian cells. Aflatoxin B1 in concentrations between 0.01 and 0.1 microgram/ml inhibits DNA synthesis in African green monkey cells in culture, but has little effect on RNA synthesis and no effect on protein synthesis. The drug even at concentrations up to 1.0 microgram/ml does not interfere with DNA repair promoted by ultraviolet irradiation nor does it induce DNA repair. The inhibition of DNA synthesis attains maximum values 3 h after addition of aflatoxin B1 and is irreversible upon removal of the drug. Profiles of pulselabeled DNA sedimented in alkaline sucrose gradients indicate that aflatoxin B1 blocks initiation of replication rather than elongation.


[In vitro synthesis of cytokinins in isolated roots of lupin (Lupinus albus L.) treated with lectins extracted from cotyledons and leaves]. The synthesis of cytokinins in isolated roots of Lupinus albus L. cultured under sterile conditions, seems to be induced by leaf proteins and lectins extracted from the cotyledons. Immunochemical methods have been used to prove that the leaf proteins were lectins too, quite different from those coming from cotyledons, but having the same effect on the root cytokinins synthesis.


[Effect of gamma radiation on organs and cells of higher plants cultivated in vitro. Dose effect on survival of axillary buds of haploid and diploid Nicotiana sylvestris and Nicotiana tabacum]. The Dose/Action relationship between gamma irradiation and bud survival, plotted on log-linear axes, produces a plateau (no decrease in survival) followed by a straight line decrease. The length of the plateau and the slope of the line appear to depend on the degree of ploïdy and the structure of the genome. There could be redondant parts in the genome of Nicotiana sylvestris.


[Trend of of stature in France].

[Trend of of stature in France]. The average stature of 23,400 young adults was 172.33 cm in 1974; it is not the final size because they were 18 to 20 years old. Compared to previous data, we note that the rate of increase grows: it was of 0.3 cm every 10 years at the beginning of the century, of 1 cm in the middle of this century, actually it reaches 1.7 cm per ten years. Studying the correlations between the increase of stature and the variations of some factors during this century, we find multiple correlations accounting for the conditions of life, without a predominant factor. Among the sample of 1974, we find again the same result. The genetic factors (consanguinity, exogamy) show more modest correlations than mesological factors. The mental capacities show the strongest correlation, but does not explain the tendency occuring one in a hundred year. We still do not know why children grow quicker and reach a final bigger size than in the past.


[Demonstration of catecholaminergic neurons in rat retina by fluorescence histochemistry on cryostat sections]. A fluorescence histochemical technique using glyoxylic acid and cryostat sections has been worked out to visualize the dopamine-containing neurons of the retina. It allows the demonstration of catecholaminergic junctional cells and alloganglion cells, classically described. Moreover, the observation of some fluorescent fibers in the external zone of the inner nuclear layer, in contact with the outer plexiform, suggests the presence of catecholamine-containing interplexiform cells, in the Rat retina.


[Differentiation antigens in keratinocytes]. By means of indirect immunofluorescence with human sera it has been demonstrated that cytoplasmic components of the basal cell layer showed antigenic differences as compared to the upper cell layers. Moreover there were differences whether the cells were involved in a mucous, a parakeratinized or an orthokeratinized differentiation.


[Effect of diet on the mitotic activity and rate of cytolysis of intestinal epithelial cells in tadpoles of the common toad, Bufo bufo (Amphibia, Anura)]. Effects of diet on the mitotic activity and cellular mortality rate of the intestinal epithelium cells have been examined in Toad tadpoles. As yolk is utilized, the composition of diet has little effect on these 2 parameters. As development goes on, the cellular mortality rate increases with dietary carbohydrate, fat or protein supplementation. But only the fats affect the mitotic activity.


[Comparative study of the glycosidases of 2 Lepidoptera wood-eating Cossidae (Cossus cossus L., and Zeuzera pyrina L.) and various wood-eating Coleoptera]. The authors present here the results of their research concerning the study of the osidases of the caterpillars Cossus cossus L. and Zeuzera pyrina L. (Lepidoptera Cossidae). Its enzyme equipment shows very important differences compared to the different species of Scolytidae, Cerambycidae, Curculionidae and Buprestidae. The differences are lie especially in the absence of some osidases acting on polysaccharides (hémicelluloses and cellulose).


[Scanning electron microscopy study of spinal cord nerve cells from chick embryos cultured in vitro with poly-L-lysine]. Chick embryo nerve cells from the lumbo-sacral spinal cord have been isolated by trypsinisation and cultivated in Rose chambers on polylysine-L as a substrate. The cells are analysed by scanning electron microscopy. The mode of adherence of these cells to the substrate and the modifications of the surface of the neuroblasts during their transformation into neurocytes are studied.


[Increase in spontaneous beating frequency in rat heart cells cultured in homologous serum]. Rat serum at different concentrations added to cultured Rat heart cells medium increased spontaneous beating frequency of myoblasts. This increase occurred instantaneously and lasted more than 24 hrs. It was related to the serum concentration used. Electrophysiological recording showed a decrease in the iso-electric phase duration of membrane potential, with no change in action potential. In spite of the beating frequency increase, cells remained sensitive to the chronotrope positive action induced by Isoprenaline. There was no difference between male and female sera. The global results could partly be explained by the action of Ca++ in Rat serum.


[Consequence of heterospecific cytoplasmic graft on gastrulation of Bufo bufo L. (Amphibia, Anura)]. Bufo bufo nuclei were grafted in virgin and enucleated Bufo calamita eggs. In these conditions embryonnic development was stopped at the early gastrula stage in 92% of the recipient eggs. For accomparative analysis Bufo calamita cytoplasm was injected into fertilized Bufo bufo eggs and produce arrest of development at the early gastrula stage. The progressive enhancement of this development inhibition was related to the increasing of the injected cytoplasm volume.


[Cholinesterase activity and expression of axial teratogenesis in quail embryo exposed to organophosphates]. The expression of the axial terotogenesis and the cholinesterasic activities have been studied simultaneously in the Quail embryo. High concentration of malathion (1 000 microgram) slightly reduces the cholinesterasic activities and does not produce morphogenetic disturbance. Bidrin (250 microgram) and parathion (100 microgram), strongly inhibit the cholinesterasic activities producing drastic axial deformities. The use of graduated concentrations of parathion shows that these axial abnormalities take place with a high level of cholinesterase inhibition. With organophosphorus, there is a good correlation between the axial teratogenesis and the cholinesterase inactivation.


[Genetic tolerance to alcohol in Drosophila: comparison of the effects of selection in D. melanogaster and D. simulans]. A strain of D. simulans and 3 strains of D. melanogaster having different initial levels of alcohol tolerance were submitted to increasing selection for at least 30 generations. In melanogaster, the relative efficiency of selection was inversely related to the initial level. In simulans, whose natural tolerance is particularly low, only a small increase was obtained. In all cases, tolerance increased progressively and could be considered as a quantitative character. These results are probably due to modifier genes of the alcohol dehydrogenase locus.


[Non-enzymatic active transport in vitro. Conversion of chemical to osmotic energy]. The active transport of ammonia gas was obtained with an asymmetric composite membrane-model using H+ as carrier and the formation of water as chemical energy source. The experimental molecular pump externally limited by two silicone films permeable to gasses but not to liquids or ions is separated into two liquid layers by a central cation-exchange membrane. The first acid layer produces the aspiration of NH3, due to NH4+ formation, through the inlet silicone film; NH4+ is transferred to the second alkaline layer through the ion exchange membrane, by interdiffusion with K+; there NH4+ reacts with OH-, water is formed and NH3 is expelled throught the oulet silicone film. This new pump enlarges the applicability of in vitro active transport to non-enzymatic systems and energy sources different from ATP.


[Initiation of transcription and translation in E. coli nucleoids]. The initiation of both transcription and translation occurs in membrane-associated nucleoid of E. coli without the addition of cytoplasmic fraction. Initiation of translation, however, is stimulated by adjunction of S 165. Our results suggest that the system is limited in synthesizing F-met-tRNA. The capacity of nucleoid-extracted ribosomes to form initiation complexes is only slightly higher than that of supernatant ribosomes. RNA synthesis is partially rifampicin-sensitive, which implies that initiation of new chains takes place in our system.


[Synthetic and biological activity of 25R and 25S diastereoisomers of dihydroxy-25,26 cholecalciferol (25,25(OH)2D3)]. The separation of 5-cholestene-3 beta, 25 (RS), 25-triol 3,26-diacetate into the diastereoisomers 25R and 25S by means of high pressure liquid chromatography (HPLC) is described. Their absolute configuration cannot be yet established. The less polar diastereoisomer is arbitrarily called 25 zeta1 and the more polar one 25 zeta2. Bromination, dehydrobromination and ultraviolet irradiation conducted to 25 zeta1, 26(OH2D3 and 25 zeta2, 26(OH)2D3 respectively. Their biological activity is described.


[Toxicokinetic study of vanadium after intramuscular and intratracheal administration to rats]. The toxicokinetic study, made in the rat with 48V under VOCl2, shows that vanadium does not accumulate in the system. 66% of the radioactivity is found in urines 24 hrs. after the inoculation by intramuscular method. After intratracheal deposit, a part of the vanadium is eliminated very rapidly. The other which is lower is fixed on the pulmonary tissues.


[Presence of "pancreatic polypeptide" cells, and gastrin immunoreactivity in immuno-induced exocrine pancreas carcinoma]. 1) In electively immuno-induced carcinomas of the exocrine pancrease in Mice, where A (glucagon) and B (insulin) endocrine cells persist, cells with a pancreatic polypeptide immunoreactivity are also detected, even in late evolution stages. These cells, like D cells, containing somatostatin, are localized only in the pancreatic remains surrounding the anaplasic carcinomatous tissue: islets, adenomatous parenchyma, and ductular epithelium. Ultrastructure of these cells shows their active elaboration of numerous chracteristic secretion granules. (2) Immunocytoenzymatic detection of gastrin is negative in the exocrine and endocrine pancreatic tissues. However one of the anti-gastrin sera used gives a positive reaction, in some carinomatous cells only. Does this immunoreactivity characterize a polypeptide specific to the pancreatic carcinomatous cell?


[The network of middle meningeal veins in Ponginae (Catarhini, Anthropormorpha)]. The grooves traced by the middle meningeal veins on the endocranial wall in the Ponginae show a particular pattern for each genus, with numerous early characteristics: important frontal branch; anterior branch reduced; occipital origin of the posterior branch and constancy of the petrosquamous sinus.


[Influence of vitamin A deficiency on thyroxinemia in the rat]. During the 9 post-weaning weeks there is not in the vitamin A-deficient Rats the regular decrease of the thyroxinemia which occurs in the control Rats. So the vitamin A-deficient Rats studied in plateau of weight have a total thyroxinemia greater than that of control Rats (+71%). It is possible to speculate that numerous symptoms of the deficiency are the result of this hyperthyroxinemia.


[Ultrastructural study of the glomerular filtration barrier and of tubular reabsorption with anti-peroxidase antibodies and their fragments]. Using anti-peroxidase Sheep IgG or their pepsic or papainic fragments intravenously injected to Wistar Munich normal Rats, the glomerular filtration barrier was localized at the lamina densa in ultrastructural studies. No evidence was found favoring the existence of a second barrier. The filtration barrier is absolute for the IgG but not for the pepsic and especially the papainic fragments which are reabsorbed by the proximal tubule.


[Stabilization of operant responses during a program of variable interval reinforcement as a preliminary investigation of sensory thresholds using conditioned suppression in the cat]. Cats were trained to press a key during a variable interval schedule  of reinforcement with a limited hold contingency. The main modifications of the response rate were observed when the subject missed one reinforcement or obtained more than one reinforcement during the limited hold. The existence of a zone of lesser variability in the mean response rate is shown to be linked to the occurrence of the last reinforcement. This result suggests an original methodological contingency concerning the use of conditioned suppression in psychophysics. The schedule of sensory stimulation should be established for each subject during that period of lesser variability between two reinforcements.


[Comparison in genetically obese and normal rats in the secretion of lipids synthesized from labeled lauric and oleic acids and glycerol in isolated perfused liver]. (1) Isolated livers of previously fasted fafa and Wistar Rats are perfused with labelled oleic acid and glycerol. Two pools of synthesized lipids are studied: --a pool of liver lipids: labelled TG 16:0, 16:0, 18:1, 16:0, 18:1, 18:1 and 18:1, 18:1, 18:1 are synthesized more by the fafa than by the Wistar Rat liver, The TG 16:0, 18:1, 18:2 appears in the liver of the 2 rat strains. After a 30 min. perfusion, the PL are synthesized less by the fafa than by Wistar Rat liver; --a pool of lipids released in the circulation. The labelled tG 16:0, 18:1, 18:2, are increased in the perfusate of fafa rat. The labelled TG 18:1, 18:1, 18:2 and 18:1, 18:2, 18:2 are in the same amount. (2) The liver synthesis of TG 12:0, 12:0, 12:0 is demonstrated in the fafa Rat by a lauric acid perfusion. This TG is not present in circulation, when a Wistar Rat liver synthesizes and releases with this TG, TG containing 1 or 2 molecules of lauric acid.


[Effect of some phosphonic amino acids on the activity of central neurons]. Microiontophoretic applications of DL-2-amino-3-phosphonopropionic, DL-3-amino-4-phosphonobutyric, aminomethylphosphonic, 2-aminoethylphosphonic and 3-aminopropylphosphonic acids in the course of extracellular recordings of central neurons in the Rat resulted in effects which appeared similar to those observed with their carboxylic analogs. The involvement of the same post-synaptic receptors is suggested.


[Comparative immunocytological study of prolactin and somatotropin cells in Alytes obstetricans (Laur.) tadpoles raised in groups or isolated]. In the anterior pituitary of Alytes obstetricans Tadpoles in premetamorphic stages, two cell types were localized by cytoimmunological techniques: orangeophilic cells secreting a prolactin-like hormone in the anterior and median region and erythrosinophilic cells secreting growth hormone in a more caudal situation. Both cells are more numerous and stimulated in grouped Tadpoles than in isolated ones.


[Development of plasma cortisol in calves from birth to 14 days of age]. Plasma cortisol was recorded in 15 calves from birth to 14 days of age by a radio-immunoassay technique. At birth mean cortisol value is 67.3 ng/ml; 6 hrs. later it decreases by 58.4% then it gradually diminishes and about 14 days after, it reaches adult levels (5.1 ng/ml).


[A pullulation cycle with violent crash in a tropical lizard]. According to a succession of samples taken at Ihotry, Madagascar, Lygodactylus tuberifer, a very rare gecko in the biotope sampled for Lygodactylus verticillatus in 1965, invaded the latter's habitat until its population reached, in the sampled biotope and using the L. verticillatus population as a gauge, an almost 700-fold increase by the end of 1972. Population growth then stopped abruptly, and a steep crash brought L. tuberifer down to 31 times less individuals within six months, whereupon sampling was discontinued.


[Lithium exchange in from epithelium: determination of unidirectional flux using the stable isotopes 6Li and 7Li in an ionic analyzer]. The use of the stable isotopes 6 and 7 of lithium, and detection with the ionic analyser, allow the measurement of unidirectional transepithelial Li-fluxes, between "external" and "internal" solutions which both contain 80% Na and 20% Li. Efflux was found to be bigger than influx. An important lag-phase on the curve, reveals the interference of a Li-compartment, with a high capacity, in the epithelium itself.


[Isolation of structural glycoproteins from human placenta]. Microfibrils about 100 A wide are isolated by mechanical procedures (sieving and ultrasonic disintegration from villosities of human placenta. Amino acid and carbohydrate compositions seem to be related to structural glycoproteins described before in connective tissues.


[Effects of Tabermanthe iboga H. Bn. alkaloids on the isolated organ responses to catecholamines and the role of calcium exchanges. Tabernanthine]. Using isolated Rat duodenum previously decalcified, the authors have investigated the effect of tabernanthine on the increase of tonus brought about by addition of calcium ions at different concentrations. The observed potentiating effect of tabernanthine towards the calcium responses may be pointed out concerning the mechanism of sensitizing effect of this alkaloid on the responses of isolated organs to catecholamines such as noradrenaline and dopamine.


[Behavior of some microorganisms cultivated in the presence of irradiated maize starch]. The bactericidal effect of water soluble radiolysis products of Maize starch on Escherichia coli cultures declines when the initial population grows. This toxicity varies with the culture environment and the bacterial species: Bacillus subtilis, Lactobacillus plantarum, Streptococcus faecalis, Enterobacter sp. Moreover, for the eucaryote cell Saccharomyces cerevisiae, wild strain or muting "small colonies", only the generating time is altered by the active parts of radiolysis products. The results are analysed with regard to the hypothesis that the hydrogen peroxide is responsible for this toxicity.


[An hypothesis for the process of selection at the subcellular level leading to the appearance of new clones]. According to the hypothesis we propose, the stimulation of one lymphocyte by an antigen induces the simultaneous expression of a great diversity of immunoglobulins of different specificities. Each molecular species is associated with the corresponding mRNA  within a subcellular structure: the ergastoplasmic cisterna. It has been shown that in some responding lymphocytes at an early stage of the immune response a few such cisternae are loaded with antibodies while most of the cisternae are synthesizing non specific immunoglobulins. The main point of our proposal is that the selective action of antigen bears on these cisternae and that the mRNA corresponding to the immunoglobulins fitting best to the antigen is transcribed to DNA which is then inserted into the genome. This cell and its progeny become thereafter a monospecific clone submitted to regulation as an element of the network.


[Serological identification of an antigen associated with acute lymphoid leukemia]. Using as references a lymphoblastoid cell line established from the pleural effusion of a lymphosarcoma patient and the corresponding autochtonous reactive serum, absorption typing assays resulted in the identification of a cell surface antigen associated with acute lymphoid leukaemia. This antigen, provisionally termed PON, may also be demonstrated on the cells of some acute myelomonocytic leukaemias and lymphosarcomas.


[In vitro malignant transformation of fetal hamster brain cells by methylnitrosourea]. Using primary cultures originating from 14 day old fetal Hamster brain, we have obtained a cell line with glial morphology. These cell remain non transplantable during the first year of in vitro culture, but undergo spontaneous transformation during the second year. Following prolonged contact of the glial-like  cells with 25 to 50 microgram/ml of methylnitrosourea (MNU), a malignant transformation is observed 5 months after the treatment. The lowest concentrations of (MNU) do not cause malignant transformation, but seem to inhibit (or postpone) the spontaneous transformation. After MNU treatment, cells retain their glial nature.


[Release of synthesized lipids by isolated Wistar rat liver perfused by labelled oleic acid and glycerol]. After perfusions with oleic acid (9, 10-3H) and glycerol (1-14C) of isolated livers from wistar Rats, previously subjected to fasting, the study of the TG and PL synthesized by the liver and released in the circulation gives of evidence similar ways of metabolising TG and PL. Two liver pools are present: -- a storage pool, built with slow exchanges of AG of endogenous glycerolipids. In our experiments, the TG: 16 : 0 18 : 1 18: 2 and 16 : 0 18 : 1 18 : 1 and the PL: PE and PC are the glycerolipids of liver constitution: -- a pool of liver secretion. TG and PL are formed according to a rapid de novo synthesis using preferentially the exogenous substrates. They are released in the circulation. In our experiments, the TG secreted are the TG 18 : 1 18 : 1 18 : 1 and 16 : 0 18 : 1 18 : 2, the PL are the PE, AP and LPC.


[Acid phosphatase activity of cytolytic T cells during cytolysis]. The localization of Golgi areas, particularly lysosomal bodies detected by their acid phosphatase activities, has been determined in the cytotoxic lymphocytes conjugated to their target cell.  The study points out the preferential situation of these organelles close to the contact area between the two cells during the target cell lysis.


[Cytochemical study of leucocytes of DBA/2 Mice after leukemia L1210 tumor graft]. The growth of L 1210 leukemia in DBA/2 strain mouse, provokes in the grafted animals intraleucocytic enzymatic modifications. As increase of acid phosphatase and a decrease of beta-glucuronidase were observed in the lymphocytes, the level of polymorphonuclear non-specific esterase being decreased. The implications of these modifications in the host response toward the tumor is discussed.


[Germ cell colonization of gonads in experimental quail twin embryos (Coturnix coturnix japonica)]. At the same development stage, two Quail twin embryos from right and left halves of a blastoderm contain together as many germ cells as a normal embryol. These are asymmetricaly distributed between the twins as between the right and left genital ridges of control embryos.


[Relations between magnesium, erythrocyte zinc and HL-A groups]. Red blood cell and plasma magnesium and zinc levels and plasma calcium concentrations have been determined in 84 unrelated male subjects, with known HLA groups. When the subjects are classified according to their HLA--B groups, significant variations are observed for red blood cell magnesium and zinc concentrations, while no important variation is observed for HLA--A groups. These results confirm the importance of genetic factors in the regulation of Mg and Zn red blood cell concentrations.


[Kinetic study of carcinogenesis. The immune barrier and the stability of microcancer states]. We show that cancerisation presents some similarities with first order phase transitions. We analyze the barrier opposed by cytoxic cells against the proliferation of cancer cells.


[Isolation and description of a new species of Eimeria in rabbits (Orychtolagus cuniculus) : Eimeria pellerdyi P. Coudert, 1977 (Sporozoa, Coccidia)]. Several pure isolates of Coccidia have been obtained in coccidia-free Rabbits by methods taking advantage of differences in the duration of their life-cycle and their site of development, as well as by the inoculation of experimentally immunized animals. Among these isolates one has been shown to represent a new species for which we propose the name: Eimeria pellerdyi P. Coudert, 1977. The oocysts of this species are of medium size (21 x 30 mu), without oocystic residual body. The endogenous life-cycle is completed in 10 days. Schizogony takes place in the superficial epithelial cells of the caecum and the colon, and gamogony in the depth of the Lieberkühn's crypts of the same organs. E. perllerdyi seems to be one of the most pathogenic coccidia species in Rabbits.


[Periodic variations in motor endplate potentials]. The amplitudes of motor end-plate potentials in the Frog have been measured during repetitive stimulations of the motor nerve at frequencies between 0,5 and 30 Hz. A serial analysis showed that cyclic variations of these amplitudes were superimposed on the random fluctuation of epp due to the quantal nature of transmitter release. The period of these cyclic variations varied between 3 and 10 stimulations. This period was not significantly related to the frequency of the stimulation. The frequency spectrum analysis of the epp amplitudes showed similar values for the period of the cyclic variation of epp. The same kind of analysis applied to a binomial series of random numbers did not significantly present periodic fluctuations. The same analysis was applied to mean amplitudes of groups of 5 to 120 successive epps at the same end-plate. Periodic fluctuations were identified with periods of about 10 to 180 sec. It is suggested that periodic failures of nerve spike propagation in nerve terminals at sites of low safety factor, as at branchings, are responsible for the observed cyclic variation of epp.


[Antidromic responses evoked in the central end of the phrenic nerve by stimulation of the ipsilateral dorsal column in the cat]. In 15 adult cats under nembutal anaesthesia the dorsal columns have been stimulated at the level of the first and the second cervical segments. Under these conditions antidromically evoked responses appear both on the ipsilateral radial and phrenic nerves. Some of the afferent phrenic fibres thus activated may be related to the diaphragm muscle receptors. In some experiments a group of thin fibres (conduction velocity comprised between 16-20 m/sec) were also activated.


[Radio-immunologic determination of hypophyseal vasotocin by Phoxinus laevis during experimental modification of osmotic equilibrium]. Hypophysial vasotocin of Phoxinus laevis is determined by radio-immunoassay. With different sea water dilutions it is shown that hypophysial vasotocin concentration varies with ambient salinity. This fact agrees with histological pictures. Moreover, in comparison with the results of other authors, it is established that the hypophysial morphological modifications appeared only after the hormonal changes.


[Determination of the molecular weight of vitellogenin and of lipovitellins of Orchestia gammarella, Crustacea, Amphipoda]. Vitellogenin and lipovitellins of Orchestia gammarella, tested by electrophoresis on gels of different acrylamide concentrations, following the procedure of Hedrick and Smith (1968), displays a migration pattern identical to that of proteins of respectively congruent to 4 x 10(5) (vitellogenin), congruent to 3,5 x 10(5) (lipovitellins I and I') and congruent to 5 x 10(5) (lipovitellin II) molecular weights.


[Role of calcium in the reinitiation of oocyte meiosis in Sabellaria alveolata (L.) (Annelida, Polychaeta)]. Meiotic maturation is triggered by ionophores A 23187 and X 537 A, even in absence of extracellular calcium. CaMg free medium alone initiates 100% maturations while Ca free SW triggers varying percentages of maturation and Mg free SW has no effect.


[Scanning electron microscopy study of membrane modification of blastomeres in the first stages of ovum development in trout (Salmo irideus Gibb.)]. Our study relates to the development of the membrane relief of the blastomeres of the trout egg from the stage before their division up to gastrulation. The surface of the blastoderm shows first a more or less dense system of crests which by the time of gastrulation are replaced by microvilli distributed over the whole surface of the enveloping layer. The deep blastomeres, loosely connected to each other by lamellipodes and filopodes produce only a few projections of their membranes and these are only semispherical bodies. Possible roles of the microvillosities in the respiratory exchange of the egg and in the motility of the enveloping layer, are considered.


[Cytotoxic and antitumor activity of a new series of heterocyclic compounds: dipyrido (4,3-b) (3,4-f) indoles]. Among newly synthesized compounds derived from the dipyrido [4,3-b] [3,4-f] indole nucleus, two have proved to be particularly active in vitro and in vivo. Their cytotoxic effects on cultured cells have been determined. At non toxic doses, they displayed a pronounced inhibitory effect on experimental L1210 Leukemia. These compounds have a strong affinity for DNA molecules.


Determination of cyanide and nitroprusside in blood and plasma. A procedure was refined for quantitative isolation of cyanide by gas transfer from acidified blood or plasma samples. The cyanide was trapped in dilute alkali and quantified as the pyridine/pyrazolone complex. The within-day coefficient of variation was 2%, which increased to about 2.5% for the day-to-day variation. Nitroprusside used as a hypotensive agent in clinical medicine provides a risk of cyanide toxicity when the rate of administration or the total amount of drug given is excessive. A procedure was developed for measuring nitroprusside in the plasma of man and animals. Nitroprusside in the sample is quantitatively converted to cyanide by incubation with cystein solution at slightly alkaline pH. Methemoglobin is added to combine with the cyanide formed and prevent its destruction. On acidification, the total amount of cyanide originally present as free cyanide or as nitroprusside is liberated as HCN, isolated by gas transfer into a sodium hydroxide trap, and quantified by spectrophotometry. Nitroprusside present in the sample is calculated from the increase in cyanide observed in the cysteine-treated sample compared to that obtained without cysteine treatment. The method has been used to estimate in vitro stability of nitroprusside in aqueous solution, blood, and plasma. Blood cyanide and plasma nitroprusside concentrations were measured when sodium nitroprusside was infused into a baboon. Over 90% of the nitroprusside in blood is present in the plasma, suggesting that the drug crosses the erythrocyte membrane slowly.


Radioimmunoassay of parathyroid hormone (parathyrin) in monkey and man. A radioimmunoassay for rhesus monkey and human immunoreactive parathyrin was developed in which a selected anti-bovine parathyrin antiserum, radioiodinated purified bovine parathyrin tracer, and human parathyroid tissue-culture media standards were used. The resulting data indicate that (a) the method is sensitive, specific, accurate and reproducible; (b) it is valid for both the rhesus monkey and the human; (c) the serum immunoreactive parathyrin concentration of the monkey is essentially the same as that in man; (d) monkey immunoreactive parathyrin responds to changes in serum calcium concentration similarly to that in man; and (e) the rhesus monkey is therefore a suitable species in which to study parathyroid physiology, from which conclusions can be applied to the human.


A new variant mucolipidosis: biochemical investigations on two siblings. Biochemical studies are presented on two siblings with some features of Mucolipidosis III, but with distinctive clinical findings. Levels of beta-galatosidase, alpha-mannosidase, beta-glucuronidase, N-acetyl-beta-glucosaminidase and alpha-fucosidase found in serum from these patients ranged from 10 to 10 times higher than normal. The ratio of heat stable to heat labile serum isoenzymes of N-acetyl-beta-glucosaminidase is considerably greater than normal. An extremely low activity of beta-galactosidase was found in fibroblasts cultured from one patient. Levels of the remaining enzymes were in the low normal range. Similarly, beta-galactosidase levels were low in heart, kidney, liver, spleen and lung of one patient who died during the course of the study. Activities of the remaining enzymes were close to normal. No excessive excretion of mucopolysaccharide was noted, however, changes in distribution of several fractions were found. Mucopolysaccharide labeled with radioactive sulfate was degraded by cultured fibroblasts at a normal rate. In addition to clinical differences, the biochemical studies further demonstrate the uniqueness of these patients.


Lysosomal enzyme activities in cultured lymphoid cell lines. Several lysosomal enzyme activities in cultured lymphoid cell lines were studied during 3 phases of cell culture; logarithmic growth phase, stationary phase and decline phase. Enzyme induction during cell growth was found in N-acetyl-hexosaminidase, beta-galactosidase and alpha-L-fucosidase, but no induction in alpha-D-mannosidase, alpha-glucosidase and beta-glucuronidase. The latter two enzymes were unchanged during all cell culture phases. A drop in alpha-L-fucosidase and alpha-D-mannosidase activity was found during the stationary and decline phases of cell culture.


Experience with a low volume ultrafiltration cell in small children*. A low volume (16 ml) ultrafiltration cell was used ten times in two small, fluid overloaded children to remove plasma water. The device was simple to use and, at slow blood flow rates (25-50 ml/minutes) and low transmembrane pressures (10-30 mm Hg), provided controlled removal of excess fluid. Although no major complications were encountered, hypothermia and hypotension (at ultrafiltrate flux rates exceeding 0.5 ml/kg/minute) were observed. The ultrafiltrate solute concentration was similar to plasma and no significant shifts in serum electrolytes were induced. The ultrafiltrate protein concentration of 64 to 2,760 mg/dl was much higher than previously reported.


Skeletal scintimaging and radiography in the diagnosis and management of Paget's disease. Experiences in sue of skeletal scintimaging, primarily with 99mTc EHDP, is reported in 108 patients with Paget's disease. The results are compared with other reports and suggest that the mean age of this sample at the time of initial diagnosis and study is somewhat younger than patients in series reported in the literature. In correlation of scintimaging with skeletal radiography only approximately 67% of lesions are seen with the latter. Lesions seen only on scintimaging primarily are associated with early symptomatic lesions and lesions seen only on radiography with older sclerotic "burned out" type lesions. Scintimaging reveals a relatively low incidence of monostotic distribution of lesions, and is superior to skeletal radiography for diagnosis of metastatic bone disease. Qualitative skeletal scintimaging is valuable for objective assessments of therapeutic management by new modes of therapy while clinical radiography is not.


Kinetics of oral ethambutol in the normal subject. Six normal adult volunteers received 15 mg/kg of ethambutol (EMB) by mouth, once as an aqueous solution and again as the commercial tablet preparation. Each dose was separated by at least 7 days. Plasma and urine samples were collected at regular intervals for up to 24 and 72 hr, respectively. Peak plasma concentrations ranged from 3.25 to 5.62 mcg/ml, 2 to 4 hr after tablet dosage. Earlier peak times were found after administering the solution. For plasma concentrations up to 12 hr there was a distinct distribution phase followed by an apparent elimination phase with a mean half-life (t 1/2) (+/- SD) of 4.06 +/- 0.53 and 4.78 +/- 0.41 hr for the tablet and the solution, respectively. Excretion rate plots exhibited similar t 1/2 values for the apparent elimination phase. An even longer t 1/2 of approximately 10 hr was evident from 24-hr plasma samples and urinary excretion measurements up to 72 hr. Unchanged drug excreted in the urine averaged 61.1 +/- 3.8% of the dose for the tablet and 63.4 +/- 2.6% for the solution. Plasma protein binding for ethambutol determined by equilibrium dialysis and ultrafiltration was approximately 20% to 30%. The concentration ratio of ethambutol in erythrocytes to plasma ranged from 1.1 to 1.6.


The construction of a pharmacokinetic model for the disposition of polychlorinated biphenyls in the rat. The construction of a preliminary pharmacokinetic model for the distribution, long-term storage sites, excretion, and metabolism of selected polychlorinated biphenyls (PCBs) in the rat is described. Following intravenous administration of radioactive PCBs, several metaboiltes of each PCB isomer were detected in urine or feces, excreted primarily as glucuronide conjugates. The relative and absolute amount of metabolites excreted depended upon the degree of chlorination and the position of the chlorine on the biphenyl molecule. Concerning long-term storage sties, an unanticipated finding was accumulation in skin, as revealed by the particularly long half-life of the 6-CB isomer in skin. A flow diagram of the model is presented, as are the differential equations, solved by computer for a given dose schedule, for the individual mass balances on parent and metabolite in each of the compartments that represent the organs or regions in which the concentration is assumed to be uniform. Low-level, long-term doses of PCBs produce a variety of toxicologic symptoms which appear only after long-time exposure. Such models should be useful in explaining and predicting the toxicities induced by exposure to PCBs and similar contaminants and the time required to reach a steady-state tissue concentration for given long-term doses.


The inducing properties of polychlorinated biphenyls on hepatic monooxygenases. The polychlorinated biphenyls (PCBs) represent a newly recognized and widely distributed category of environmental pollutants whose biologic impact on animals and man may be both substantial and highly detrimental. The pharmacologic effects of these agents on enzymes in the liver which metabolize drugs and other foreign compounds, such as carcinogens, are powerful and long lasting. PCBs mimic the effects produced on these enzymes by drugs, such as phenobarbital, and carcinogens, such as 3-methylcholanthrene. They are potent inducers of cytochromes P-45O and P-448 and associated enzymic activities. Further, these chemicals can cross the placental barrier and be transmitted through maternal milk to the newborn infant causing marked increases in drug biotransformation enzymes in the fetus and the neonate. Studies with the use of microscope immersion oils containing PCBs show that application of minute amounts of these oils to the skin of experimental animals results in a marked induction of the drug-and carcinogen-metabolizing enzymes. These findings suggest that even trivial skin exposure to chemicals, such as PCBs, can have significant and perhaps harmful biologic effects in man.


Inhibition of prostaglandin synthesis and leucocyte migration by flurbiprofen. The carrageenan air pouch technique in the rat was used to investigate the effects of flurbiprofen, a non-steroidal anti-inflammatory agent, on prostaglandin production and leucocyte migration. tthere is a suggestion that flurbiprofen was capable of inhibiting prostaglandin synthesis at doses lower than those which were effective in reducing leucocyte migration. Therefore, these two effects may reflect independent actions of the drug. The possible clinical relevance of these experiments has been noted since the effects of flurbiprofen on prostaglandin synthesis and leucocyte migration are produced in the rat at peak plasma concentrations which are less than those found in man after a single dose of 50 mg.


[Paralysis in hypophosphataemia (author's transl)]. Neuromuscular syndromes and respiratory insufficiency may be caused by hypophosphataemia. This complication may occur particularly in patients with malnutrition who receive parenteral glucose, as two examples show.


[Action of sustained release nitroglycerin on a pulmonary artery pressure in coronary heart disease (author's transl)]. In 12 patients with coronary heart disease and increased left ventricular filling pressure the pressure lowering effect of an oral long-acting nitroglycerin preparation (Sustac-Retard forte) was investigated at rest (n = 6) and during exercise (n = 6). The systolic and end-diastolic pulmonary artery pressure decreased significantly for up to 6 hours after the ingestion of 6.5 mg of nitroglycerin. The most marked pressure changes in the pulmonary circulation occurred 2 to 4 hours after ingestion of the tablets. All patients noticed reduction of dyspnoea and (or) anginal pain.


[Extracorporeal perfusion with baboon liver in the treatment of hepatic coma (author's transl)]. In 11 patients with hepatic coma (stage IV and V according to Abouna) extracorporeal haemoperfusion using the Scribner shunt (radial or profunda femoris artery) was performed over 12 to 27 hours with 22 baboon and one human livers. Eight patients emerged from coma, six of them showed sufficient regeneration of the diseased liver. Four patients were discharged as cured, one patient died of acute pancreatic necrosis, a further one due to bleeding from an old gastric ulcer. In the 2 remaining patients the coma recurred within 48 hours. Tree patients never came round from coma. After perfusion no antibodies against baboon proteins were demonstrable in the patients. Thus there is very little danger of an anaphylactic reaction when perfusion is repeated. The titre of preformed cytotoxic antibodies against baboon cells in patients' serum rises only after 1-2 weeks and decreases again after 4 weeks. In our experience extracorporeal liver perfusion with baboon or human livers is the most promising method for treatment of hepatic coma.


[Etiopathogenetical diagnosis and therapy of epilepsy (tentative application of some neurophysiological data)(author's transl)]. A purely symptomatological classification of epilepsies can be substituted by diagnostical determination of etiopathogenetical components, which take part in the origin and evolution of the pathological process in individual cases. Usually it can be done by simple diagnostical processing. The etiopathogenetical diagnosis can also contribute to a less empirical and more rational use of therapeutical means.


[Epilepsy and headaches (author's transl)]. The controversial relations between migraine and vascular headache on one hand, epilepsy on the other hand are once more discussed: survey of the arguments for a more than fortuitous connexion, taken from literature and general experience. Critical analysis of the personal case material. Discussion of some specific groups of patients with various combinations of both syndromes: long antecedents of headaches, leading up to sporadic epileptic attacks, focal or generalized; clinical seizures under photic stimulation (10% of the cases with chronic headaches without organic lesions); headaches in the latency period of symptomatic epilepsy; cases of seeming transition between the two syndromes; headaches as a substitute, an aura or as a component of the epileptic seizure, with clearly distinctive features between generalized and focal epilepsy: in patients with bilateral EEG paroxysms, headaches are usually diffuse or bilateral, in those with epileptogenic foci, headaches, if consistently localized, are always reported to be homolateral to the focus. Considerations concerning pathogenesis include the familiar hypothesis of hypoxic discharges following migrainous vasoconstriction, as well as secondary vascular headaches induced by focal epileptic activity. Headaches caused by excessive discharges in the sensory representation areas (H. Jackson) must be rare. Whether increased neuronal activity in the hypothalamus may be responsible for the migraine syndrome (Herberg), possibly in connection with biogenic amines, remains in open question.


[Spontaneous and evoked EEG-activity during one-second light-stimulation (author's transl)]. EEG data were recorded in 13 students during one-second light-stimulation with eyes closed and sometimes eyes opened, from central and occipital regions. The background EEG was computer-analyzed in the alpha-band using the power time course where a short decrease in power was indicative of a phasic desynchronization of the rhythmic activity within the alpha-band. The maximal desynchronization was observed in the occipital region independent of eyes-opened or eyes-closed conditions. With eyes closed a reinforced power decrease was found 0.25-0.5 sec after the on- and offset of light-stimulation, which was interpreted as "on"- and "off"- effect of the background EEG activity. Parallel with the on- and off-effect a slow potential change occurred in the evoked responses. The behaviour of the background activity during 1 sec light-stimulation was intramodality specific in contrast to the evoked response which showed an intramodality unspecific behaviour with maximal amplitude in the central region.


[Spike discharges on stimulation with diffuse and patterned light in epileptic and non-epileptic patients (author's transl)]. The effects of photic stimulation with intermittent diffuse light and patterned flash were compared in 587 patients. The diagnosis of epilepsy was unquestionable in 216 patients and suspected in 150 cases while 221 patients had no evidence of epileptic attacks. None of these patients had a history of photosensitive epilepsy. A grid pattern with squares subtending 22' of arc was used in the first 28 patients while the following 379 patients were tested with a checkerboard pattern of corresponding size. In 51 cases generalized spikes or spike-waves and/or occipital spikes were obtained. These discharges were elicited by diffuse light as well as by patterned flash in 37 patients. 11 cases were insensitive to pattern. In 3 cases spike discharges were seen only with patterned light while diffuse light was without effect. The response consisted in 13 cases of generalized spikes and spike-waves. 12 of these had an unquestionable epilepsy. Occipital spikes only were seen in 38 patients; 22 of these suffered from epilepsy. Patterned light was in no case found to be more effective than diffuse light for eliciting generalized epileptic discharges. In the 3 cases where only patterned light produced spikes, these were restricted to occipital regions. As occipital spikes do not have the same significance for the diagnosis of epilepsy as generalized spikes the addition of patterned flash to diffuse light stimulation does not seem to be of great value.


[Age dependency of muscular action potential duration in the normal human electromyography (author's transl)]. The medium duration of muscular action potential in both the m. quadriceps and m. gastrocnemius of 188 subjects with normal neurological status between the ages of 15 and 70 were measured. Following results were found: 1. The duration of action potential in the m. quadriceps shows an increase from the age of 15 to 40, beyond which only a partial non-significant increase occurs. 2. The duration of action potential in the m. gastrocnemius also shows an increase up to the age of 40, after which no further increase occurs.


[A Bell"s palsy of long standing, and its rehabilitation. An electromyographic documentation. (author's transl)]. We examined a 31 year-old female patient who, since her first year of life and following a parotis operation, had suffered from left-sided Bell's palsy. The electromyographical examinations disclosed a complete loss of voluntary muscle control and of the trigemino-facial reflexes, although the direct responses of the facial nerve could be demonstrated with delayed latences. The findings indicated peripheral regeneration of the facial nerve with absence of central programming and reflex pathways. By means of rhythmic muscle stimulation, voluntary control and reflex excitability was re-established, to a limited extent, on the formerly inactive side within a short space of time.


Estrogen action in vitro: regulation of thyroid stimulating and other pituitary hormones in cell cultures. Primary cell cultures of ovine pituitaries can maintain production of thyroid stimulating hormone (TSH) for as long as 24 days. These cultures responded in a normal fashion to thyroxine by decreasing TSH secretion. Addition of thyrotropin releasing hormone increased TSH secretion. Physiologic levels of estradiol-17 beta (10(-11)-10(-9)M) produced a five-fold increase in secretion of TSH and a two-fold increase in intracellular TSH concentration in cell cultures. Common estrogens, but not common progestins, androgens and glucocorticoids affected TSH production. Markedly different effects of estrogen in the pituitary on follicle stimulating, luteinizing and thyroid stimulating hormones and prolactin are discussed in terms of current models of estrogen action.


Preparation of single cells from pancreatic islets of adult rat by the use of dispase. A high yield of viable single cells was attained from isolated pancreatic islets of adult rat by the sequential treatment with EDTA and Dispase. The percentage of single cells was consistently higher with EDTA-Dispase in comparison with EDTA-trypsin treatment, being 65.8 +/- 7.9% and 36.0 +/- 5.4% respectively, when more than 90% of total islet cells were viable. Excellent preservation of free islet cells dissociated with EDTA-Dispase was demonstrated morphologically by light and electron microscopy. The secretory response of dissociated B cells to glucose was stabilized earlier with EDTA-Dispase than with EDTA-trypsin treatment. The amount of insulin released into the medium was proportional to the number of cells inoculated, thus permitting the quantitative analysis of B-cell function in vitro.


Effect of thyrotropin releasing hormone on heart rate and visual evoked potentials in rats. The effect of injection of 0.3 microgram of thyrotropin releasing hormone (TRH) into the third ventricle on heart rate and photically evoked potentials in the midbrain reticular formation in urethane-anesthetized rats was studied. TRH increased the heart rate and amplitude of the visual evoked potentials within a few minutes following injection. The intraventricular injections of LHRH, consituent amino acids of TRH and intraperitoneal TSH did not exert any effect. This indicates that TRH is effective in the central nerveous system in inducing tachycardia in the rat.


Chemical sterilization of male langurs: synergistic action of alpha-chlorohydrin (U-5897) with methallibure (ICI, 33828) on the testes and epididymides of Presbytis entellus entellus Dufresne. 1. Synergistic action of alpha-chlorohydrin with methallibure (ICI, 33828) on the testicular function of Presbytis entellus entellus Dufresne has been studied. 2. Chronic administration of alpha-chlorohydrin alone (140 mg/day for 40 days) caused testicular lesion resulting in a massive atrophy of the spermatogenic elements. Epididymal epithelium was regressed and the lumen was devoid of spermatozoa. 3. alpha-Chlorohydrin inhibited the synthesis of RNA and sialic acid in the testes and epididymides. Total cholesterol per gram of testis and alkaline phosphatase activity were increased after alpha-chlorohydrin administration. 4. These effects could be achieved with a lower dose of alpha-chlorohydrin (1/4) when administered in combination with a gonadotrophin inhibitor, i. e. ICI, 33828 (Methallibure). Methallibure alone (200 mg/kg: total dose) has no damaging effects on the testes and epididymides. But it altered testicular cholesterol and enzyme activity. 5. In conclusion, an effective inhibition of spermatogenesis could be achieved by synergistic action of the two different drugs i. e. alpha-chlorohydrin and ICI, 33828 (Methallibure).


Influence of dopamine and thyrotropin releasing hormone on the volume of nuclei of prolactin cells in rat adenohypophysis in vitro. The effect of dopamine and TRH on the volume of prolactin cells nuclei in the rat anterior pituitary cultured in vitro has been investigated. A significant increase of volume of prolactin cells nuclei exposed to TRH has been shown. Dopamine had no significant influence on the volume of the nuclei of prolactin cells. The prolactin cells exposed to dopamine showed clearly an increased granulation. The obtained results suggest that dopamine exerts a stronger inhibiting effect on the release of prolactin than on its synthesis.


An experimental study on endoscopic papillotomy in monkeys. Endoscopic papillotomy would appear to have distinct advantages in non-operative treatment of common bile duct stones. To investigate the effects of this procedure on the papilla and adjacent organs, diathermy papillotomy was performed at laparotomy in three monkeys. White-cell count and levels of liver function parameters temporarily increased during the follow-up period of twelve months, suggesting that diathermy papillotomy might have brought about some pathological changes in the hepatobiliary system of monkeys, whereas no definite evidence of cholestasis or pancreatitis were noticed, and an excellent condition of papillotomy orifice and adjacent ogans was revealed at autopsy about 1 year after diathermy papillotomy.


The size and shape of human and bovine antithrombin III. Human and bovine antithrombin, purified by affinity chromatography on heparin-agarose, have been characterized with regard to chemical composition, size, shape and conformation. Both preparations were found to contain several active components of identical or similar size but different electrical charge. Amino acids and carbohydrate analyses revealed striking similarities between human and bovine antithrombin, while immunological analyses failed to demonstrate any cross-reactivity. The molecular weights were determined by sedimentation equilibrium to be 58 000 for human and 56 000 for bovine antithrombin. The small molecular weight difference suggested by these values was verified by several empirical methods of molecular weight estimation. Hydrodynamic measurements indicated that the two proteins have similar molecular shapes, both of which are slightly more extended that that of typical globular proteins. The internal folding of the two polypeptide chains is also similar, as evidenced by the identity of the far-ultraviolet circular dichroism spectra. Specifically, these analyses suggested a low alpha-helix content of both proteins. In conclusion, the marked structural similarity of human and bovine antithrombin indicates that the two proteins may also exhibit extensive functional similarities in the binding of heparin and the inhibition of various coagulation factors.


Biochemical and immunological studies on larval serum protein 1, the major haemolymph protein of Drosophila melanogaster third-instar larvae. Larval serum protein 1 is the major haemolymph protein just before puparium formation in Drosophila melanogaster. It has been purified and characterised as a family of hexamers (molecular weight 450000-480000) of three immunologically related polypeptides (molecular weight 75000-81000). Homologous proteins, present in other dipterans, are similar in structure, amino acid composition and developmental profile.


Treatment of Condyloma acuminata in male patients. The treatment of 101 male patients with venereal warts is described. Prior to the study 33 patients had been treated unsuccessfully with podophyllin. 57 of the patients showed urethral lesions while 2 also showed venereal warts in the bladder. The primary treatment was electrocoagulation in 100 patients, 58 of these being cured. Chemical agents such as ethoglucid, Verruxin and thiotepa seemed to be effective in the treatment of resistant, especially intraurethral condylomas. In 8 patients autogenous vaccination was used, 6 responding completely to the vaccination alone while the remaining 2 were cured after vaccination and excision.


Spontaneous rupture of a congenital diverticulum of the right ventricle in a 1-month-old child. Spontaneous rupture of a thin fibrous congenital subepicardial diverticulum of the right ventricle of the heart resulted in a sudden death of an 1-mth-old child. Heart catheterization with angiocardiography at 1 and 2 wk of age revealed a truncus arteriosus type A 1 with a small frontal outbulging in the level with the outflow of the right ventricle, interpreted as a blind infurdibular chamber. At autopsy this outbulging was identified as a congenital fibrous diverticulum of the right ventricle. Death was due to rupture of the diverticulum and hemopericardium. The case motivated a reviewing of the literature dealing with congenital diverticula of the right ventricle of the heart, as well as a discussion of problems with the diagnosis of the diverticulum.


Organization of the thalamo-cortical connexions to the frontal lobe in the rhesus monkey. In 25 rhesus monkeys horseradish peroxidase was injected in different parts of the frontal cortex. The retrogradely labelled thalamic neurons formed longitudinal bands, some of which crossed the internal medullary lamina, and extended from one thalamic nucleus into another. On the basis of these findings the frontal cortex was subdivided into seven transverse cortical strips which receive afferents from seven longitudinal bands of thalamic neurons. The most rostral transverse strip receives afferents from the most medial thalamic band which is oriented vertically and extends through the most medial part of the MD into the medial pulvinar. Progressively more caudally located transverse strips receive afferents from progressively more laterally located thalamic bands which in part are situated in the VL and show an increasing tilt towards the horizontal. Moreover, those parts of the various bands which are situated along the dorsal and lateral margin of the thalamus project to the medial portions of the transverse cortical strips, i.e. along the medial margin of the frontal lobe, while the other parts situated ventromedially in the thalamus project to the lateral portions of these strips, i.e. along the lateral margin of the frontal lobe. These data provide an alternative view of the organization of the thalamus and suggest that this structure contains a matrix of longitudinal cell columns which in some cases extend across specific nuclear borders and may represent the basic thalamic building blocks in respect to the thalamo-cortical connexions.


The shift-effect in the lateral geniculate body of the rhesus monkey. Responses to sudden shifts of  a  pattern far away from the receptive field (shift-effect) were found in 73 out of 81 cells of the ventral, magnocellular LGN layers, but in only 26 out of 85 cells of the dorsal, parvocellular layers. Most of the former responses were clear and excitatory, and most of the latter were weak and inhibitory. Excitatory responses were stronger for steady receptive field illumination which when turned on also yielded an excitation. No convincing dependence on the colour of the receptive field illumination was observed. The results are discussed with respect to the hypothesis of transmission of steady illumination via the shift-effect ("restoration"), and with respect to a hypothesis assigning a signaling function of low stimulus specificity to the ventral layers.


Response plasticity of neurons in auditory cortex of the rhesus monkey. Auditory-evoked responses in single neurons from rhesus monkey auditory cortex were measured under four relatively well defined behavioral and physiological conditions: (1) monkey awake and performing a simple auditory reaction time task; (2) monkey awake but not performing a task (Stage A); (3) monkey in a drowsy or Stage 1 sleep state (State B); and (4) monkey anesthetized with a short-acting nonbarbiturate anesthetic. For most units studied the response evoked by the auditory stimulus was greater in the performance condition than in the nonperformance condition. Similarly, evoked activity was usually greater in State A than in State B. Finally, evoked responses under anesthesia were usually weaker than those obtained in the unanesthetized animal. Some exceptions were noted in each case. Differences in response patterns and in rate versus intensity functions of neurons were also found to be associated with the behavioral and physiological state of the preparation. No significant changes in unit spontaneous activity associated with changes in behavioral or physiological condition were observed.


Steady-state methods for the study of placental exchange. Published and new data on steady-state exchange of tracers and oxygen are characterized by marked species differences. When the placenta is treated as an ideal diffusion cell of unknown vessel geometry and permeability, the exchange characteristics of oxygen can be used to prove that the exchange of tracers such as acetylene, nitrous oxide, tritiated water and antipyrine is entirely flow limited. The recorded patterns of transfer of flow-limited tracers reveal that some placentas are as effective as counter-current exchangers whereas others mimic the behavior of the less effective types of exchangers. These species differences in apparent geometry are unrelated to the histologic nature of the barrier. The patterns of flow-limited transfer are so similar to those of oxygen transfer that the diffusion resistance to oxygen must be small. The exchange of diffusion-limited (hydrophilic) tracers mimics exchange across capillary membranes in some species and exchange across cell membranes in others. These species differences in diffusion-limited transfer are clearly related to the histologic nature of the barrier and are independent of vessel geometry.


[Role of the sympathetic nervous system in regulating blood supply to the brain]. Cerebral vascular responses (impedance method) and the regional cerebral blood flow (H2 clearance) in visual and sensomotor cortex during direct application of noradrenaline (NA) or stimulation of cervical sympathetic nerve were studied in chronic and acute experiments on monkeys and cats. NA in concentration 0.01 mcg/ml and pH--7.3 increased regional blood flow by 10 +/- 0.8%; NA concentration 0.1 mcg/ml had no effect on the flow, and NA concentration 1 and 2 mcg/ml decreased cortical blood flow by 9 +/- 1.2%, 21 +/- 3. Changes of pH from 7.3 to 6.9 decreased the constrictory effect of NA. Electrical stimulation of preganglionic nerves in chronic experiments decreased blood flow of the stimulated hemisphere by 19 +/- 1.4%, while only by 11 +/- 2% in acute experiments. The latency of vascular reactions of alert animals was very short, the reactions reaching their maximum within 15-20 sec. In acute experiments the maximum of the reaction decreased by 50% while the latency and duration increased. The data suggest that cortical vessels are sensitive to NA at the same concentrations as in normal physiological conditions and that vasoconstriction develops in response to sympathetic activation.