The effect of chemoprophylactic use of rifampin and minocycline on rates of carriage of Neisseria meningitidis in army recruits in Finland. During an epidemic caused by sulfonamide-resistant group A Neisseria meningitidis (A SuR strain), rifampin (600 mg per day for four days) or minocycline (100 mg every 12 hr for five days) was administered as chemoprophylaxis to 1,540 unvaccinated recruits in the Finnish Armed Forces. Rates of carriage of all strains of N. meningitidis were initially reduced by 78% (from 60% to 13%) in the 389 men receiving rifampin and by 62% (from 70% to 26%) in the 1,151 men receiving minocycline but rose to approximately 30% in both groups four weeks after prophylaxis. The carriage of A SuR strains was similarly reduced. An individual follow-up of 636 trainees demonstrated a high rate of new infections. It is suggested that the long-term inefficiency of rifampin and minocycline is due to their inability to reduce the carriage rates enough to prevent further spread of infection after prophylaxis is descontinued. However, no new cases appeared among the men receiving the prophylaxis. Five strains highly resistant to rifampin were found after the use of rifampin (minimal inhibitory concentration, greater than or equal to 100 microgram/ml), but no minocycline-resistant strains were encountered. No unpleasant side effects were seen in subjects receiving either drug.


Regulation of thyrotrophin secretion by negative feedback of tri-iodothyronine on the hypothalamus. Bilateral injections of tri-iodothyronine (T3, 2 ng in 2 microliter artificial cerebrospinal fluid, CSF) were made into the hypothalami of 15 hypothyroid rhesus monkeys (Macaca mulatta) prepared with chronically implanted intrahypothalamic cannulae. In 29 out of 96 such injections, the concentration of thyrotrophin (TSH) in the plasma fell rapidly by more than 30% and returned to the basal value over the succeeding 48 h, in 13 experiments the fall was 20-30% and in the remaining 54 experiments the level of TSH was unaltered. With [125I]T3, the extent of diffusion of T3 through the hypothalamus in these experiments was shown to be very limited. The hypothalamic injection sites were subsequently identified histologically and it was found that in those experiments in which the level of TSH in the plasma had fallen, T3 had been injected into either the dorsomedial nucleus or the lateral hypothalamic area extending into the preoptic region. Injection of artificial CSF alone into these areas of the hypothalamus did not affect the concentration of TSH. Direct intrapituitary injections of T3 (4 ng) resulted in small and inconstant changes in the concentration of TSH in the plasma and injections of T3 (400 ng) into the third ventricle were without any effect. These experiments demonstrate that T3 can rapidly inhibit the secretion of TSH by a direct action upon defined parts of the hypothalamus.


[The development of urogenital organs after lateral mesoblast heterotopic graft in the toad (Bufo bufo) neurula. I. Distinct inversions of anteroposterior and dorsoventral axis of the lateral plate (author's transl)]. Anteroposterior inversion of lateral mesoblast of early toad neurula is followed by differentiation of diverse urogenital blastema, according to the transplant position before the graft. Anteroposterior polarity of lateral mesoderm is thus perfectly determined in young neurula. On the contrary, dorsoventral inversion of lateral mesoblast leads to mesodermic blastema formation according to the transplant position after the graft. Particularly, the dorsal region of the lateral plates displaced to ventral position does not form blastema. On the other hand, the ventral region which shows a dorsal position after the graft develops and produces a typical blastema. Thus, in the young neurula, the dorsoventral polarity is not yet determined in the lateral plate of the mesoblast. Such a result shows also that the ventral and posterior regions of the lateral mesoblast are competent to form blastema. Moreover, factors from dorsal origin and external to lateral mesoblast take part in urogenital organ anlagen formation.


Protection against group B meningococcal disease. II. Infection and resulting immunity in a guinea pig model. A guinea pig subcutaneous chamber model was used to evaluate the specificity of the immune response resulting from Neisseria meningitidis infection. Small numbers of meningococci easily infected the chambers. The infections persisted for 6-8 days with relatively high levels of organisms (10(5)-10(6)/milliliter) in the chambers, and were then rapidly eliminated and no organisms could be cultured beyond day 14. Clearance of infection correlated with appearance of circulating antibody. Antibody against both the protein serotype antigen and the capsular polysaccharide were induced as a result of meningococcal infection. The group-specific polysaccharide response peaked 2-3 wk after the animals were inoculated, while the type-specific protein response peaked at 5-6 wk. The animals were quite resistant to reinfection with either the homologous serogroup or serotype.


Protection against group B meningococcal disease. III. Immunogenicity of serotype 2 vaccines and specificity of protection in a guinea pig model. Protein vaccines were prepared from the serotype antigen of group B Neisseria meningitidis strain M986. The detergents Triton X-100, Emulphogene BC-720, and deoxycholate were used to removed the toxic lipopolysaccharide (LPS) portion of the serotype antigen. The LPS was most preferentially solubilized by Emulphogene. Guinea pigs were immunized with one or two doses of vaccine given intramuscularly without adjuvants and the antibody response quantitated by an enzyme-linked immunosorbant assay. Immunization with graded doses of vaccine between 25 to 200 microgram protein indicated a wide range of effective dosage and that a two-dose immunization schedule was superior to a single immunization. The vaccines elicited peak mean serum antibody levels of approximately 30 microgram/ml with bactericidal titers of 1:1,600-1:6,400. The peak antibody levels occurred 5-6 wk after immunization and persisted above preimmune levels for several months. To evaluate the protective effects of immunization, stainless steel springs were implanted subcutaneously into the guinea pigs. The resulting chambers, in unimmunized animals, could be infected with less than 100 type 2 organisms. A single 25-50 microgram dose of vaccine protected 50% of animals from challenge by 5 X 10(5) type 2 meningococci, and as little as 1 microgram vaccine significantly reduced the severity of infection. A two-dose immunization schedule was best and provided nearly complete protection for at least 4 mo against type 2 strains of meningococcal groups B, C, and Y.


Cytotoxic T-cell responses to H-Y: mapping of the Ir genes. The secondary cytotoxic responses to the male specific antigen (H-Y) in in mice show H-2 restrictions so that cytotoxic female cells must share K and/or D end antigen with the male target cells. The production of cytotoxic cells is under the control of Ir genes, thus offering the possibility of studying the function of Ir genes in H-2-restricted cytotoxic responses. There are two kinds of Ir genes regulating this response; the dominant gene in the H-2b haplotype and complementary genes in other haplotypes. Now we have been able to map the dominant gene and some of the complementary genes: the dominant genes is in IAb, and in H-2k/H-2d complementation, the Ir genes are in ICk and ICd, and in H-2k/H2s and H-2k/H-2q complementations, at least the H-2k gene is in IC.


Cytotoxic T-cell responses to H-Y: correlation with the rejection of syngeneic male skin grafts. The ability of female mice to rapidly reject syngenic male skin grafts is largely determined by dominant genes in the IB region of the H-2b halotype, whereas the ability to produce anti-H-Y cytotoxic cells is determined by a dominant gene in the IA region the H-2b halotype, or by complementary genes in the IC region of some other haplotypes. Thus, it seems that H-2-retricted anti-H-Y cytotoxic T cells are not responsible for the rejection of syngeneic male skin grafts.


The diversity of the influenza-specific primary B-cell repertoire in BALB/c mice. The primary immune response of BALB/c mice to influenza (PR8) hemagglutinin (HA), a complex protein antigen, has been examined by the splenic focus assay, and the resulting monoclonal anti-HA antibodies have been characterized by their reactivity with heterologous viruses. The analysis of the primary B-cell response to HA revealed marked differences from responses previously defined for haptenic determinants. There were following differences: (a) the frequency of HA-specific B cells in both conventional and germ-free BALB/c mice was 1 in 1.0-1.5 X 10(5) splenic B cells, which is substantially lower than the frequency of B cells responsive to various simple haptenic determinants; (b) monoclonal anti-HA antibodies were predominantly of the IgA or IgM isotypes instead of IgG, which dominates antihapten responses; and (c) after immunization, the frequency of anti-HA-specific B cells increases by 10- to 50-fold, which is much greater increase than that observed after immunization with haptenic determinants. Fine specificity analysis of primary monoclonal HA-specific antibodies revealed extensive diversity and a considerable overlap with the specificities obtained from immune mice. Given the low overall frequency of HA-specific B cells, it could be calculated that the representation of most HA-specific clonotypes within the B-cell repertoire could not exceed 1 in 10(7) B cells. These findings indicate that the primary B-cell clonotype repertoire is extremely diverse and largely antigen independent in its generation.


Activation of mouse lymphocytes by anti-immunoglobulin. I. Parameters of the proliferative response. Spleen cell cultures from young adult mice of a variety of strains were stimulated to incorporate tritiated thymidine ([3H]TdR) by a goat anti-mouse IgM antiserum and by purified anti-mu antibodies prepared from this serum. This stimulation was shown to depend upon the anti-mu activity of the antiserum. In addition, ultracentrifuged anti-mu and F(ab')2 fragments of anti-mu were shown to be stimulatory. The anti-mu preparation lacked detectable endotoxin contamination and was also shown to stimulate response by two strains (C57BL/10ScCr and C3H/HeJ) which are unresponsive to the mitogenic effects of endotoxin, while it failed to stimulate a response by cells from a mouse strain (CBA/N) which responds to endotoxin. In addition purified goat anti-mouse gamma, kappa antibodies and rabbit anti-mouse kappa-antib odies stimulated uptake of [3H]TdR by mouse spleen cells, although to a lesser degree than the anti-mu preparation. The cell density, culture requirements, and kinetics of the response are presented.


Studies on the chemical composition of lipopolysaccharide from Neisseria meningitidis group B. A lipopolysaccharide was isolated from Neisseria meningitidis group B by phenol/water extraction and purified by differential ultracentrifugation. This preparation exhibited endotoxic properties as shown by the limulus-lysate assay. Mild acid hydrolysis of the lipopolysaccharides yielded a lipid A fraction and a polysaccharide fraction. The lipid A fraction contained fatty acids, phosphorus and glucosamine. Analysis of the polysaccharide fraction revealed the presence of glucose, galactose, glucosamine, 2-keto-3-deoxyoctonic acid and phosphorus. There was no heptose.


Peptide utilization by group N streptococci. The rate of glycylleucine uptake by Group N streptococci varied widely. One strain of Streptococcus cremoris did not transport the dipeptide or utilize tripeptides. In peptide-utilizing strains, amino acid, dipeptide and tripeptide transport were distinct, although dipeptides inhibited tripeptide utilization. Specificity determinants for peptide transport and utilization were similar to those reported in Gram-negative bacteria. Peptide utilization in S. lactis was not completely dependent on the transport of intact peptides.


The effect of lipopolysaccharide composition on the ultrastructure of Pseudomonas aeruginosa. The surface structure of Pseudomonas aeruginosa PACl and PAClR and of lipopolysaccharide-defective mutants derived from them was studied by negative-staining and thin-section electron microscopy and compared with that of a rough mutant with wild-type lipopolysaccharide. The rough mutant and the parent strains had fairly smooth outer layers. Negatively stained preparations of all the mutants lacking polymerized O-antigenic sidechains, including a semi-rough mutant, showed numerous blebs on the surface. In thin sections of these mutants occasional extrusions from the surface were seen. They appeared to consist of material extruded from the outer membrane, but there was no evidence to suggest they were complete unit membranes. Polymerized O-antigenic side-chains in the lipopolysaccharide appear to be required to produce the wild-type appearance of the outer membrane in P. aeruginosa.


Electron microscopy and computerized evaluation of some partially denatured group P resistance plasmids. DNA of the R plasmids RP1, RP4 and RP8 was isolated from various hosts. The lengths of these plasmid molecules were determined by electron microscopy: RP1 and RP4 were about 19 micron long, RP8 measured 31 micron. An RP4 plasmid mutant, designated RP4a, was isolated from Escherichai coli; it was about 1 micron shorter than normal RP4 DNA. To investigate the molecular relationship between RP4, RP4a and RP8 DNAs of these plasmids were partially denatured and examined in the electron microscope. Measurements of the length and denaturation pattern of the DNA molecules were used to construct physical maps. A new computer program was devised for the alignment of the circular molecules, and the effect of variations of different parameters on the reliability of the program was tested. A comparison of the denaturation pattern of RP4 and RP8 indicated that RP8 was composed of total RP4 plus an additional DNA fragment. The RP4a mutant plasmid could be defined as a deletion mutant with loss of 1 micron DNA.


Continuous-flow size selection of Tetrahymena pyriformis ST: changes in volume, DNA, RNA and protein during synchronous growth. The cell cycle of Tetrahymena pyriformis ST was studied using synchronous cultures prepared by continuous-flow size selection. These organisms had cell cycle times (mean values 151 and 186 min in the first and second cycles respectively) similar to but not identical with the mean generation times of exponential cultures from which they were selected (mean value 165 min). The median volume of cells averaged over the duration of the cell cycle in synchronous cultures was similar to that found in exponential cultures. Total cell DNA, RNA and protein doubled during the cell cycle: there was one discrete S phase which occupied 40 to 50% of the cell cycle time during the period between the end of the selection procedure and the first synchronous division. Total cell protein and RNA increased continuously.


Correlations between anti-albumin antibodies and HBsAG in hepatic patients. A new category of autoantibodies--antipolymerized albumin antibodies (AAA)--was discovered in 1974. Studies performed from 1974 to 1976 showed their diagnosis and prognostic values in hepatic diseases; the AAA tests [immunodiffusion (ID) and hemagglutination (HS)] made possible a good estimation of the total liver cell function. Without being specific for a viral hepatitis B infection, highly significant linear correlations were found for AAA precipitin and agglutinin positivities with presence of HBsAg. High titre of AAA agglutinins unaccompanied by a positive ID test, characterise the "healthy carrier" of the HBsAg, while the isolated AAA positivity in ID is met in more severe, long-standing hepatic diseases.


Experimental respiratory syncytial virus infection of four species of primates. Four species of nonhuman primates were inoculated intranasally with 10(3.1) to 10(3.7) plaque forming units (pfu) of respiratory syncytial (RS) virus. Adults squirrel monkeys and newborn rhesus monkeys became infected and shed small quantities (peak titer 10(2.0) pfu/ml of nasopharyngeal swab specimen) of virus, but illness did not develop. Infant cebus monkeys aged 2 months became infected, shed 10(2.3) to 10(3.8) pfu/ml of nasopharyngeal swab specimen, but did not become ill. Chimpanzees aged 15 to 18 months shed a large quantity of virus, up to 10(6.0) pfu/ml of nasopharyngeal swab specimen and developed an upper respiratory illness. Chimpanzees are proposed as a possible animal model for future study of the immunopathology of RS virus disease and for in vivo evaluation of attenuated live virus vaccine candidates.


Acute optic neuritis: a virological study in relation to multiple sclerosis. Previous ultrastructural examination of peripheral blood lymphocytes revealed the presence of intranuclear filamentous structures in multiple sclerosis (MS) and in some optic neuritis (ON) patients. The present investigation was undertaken in the attempt to correlate the presence of such structures with the etiology of ON and MS and possibly to demonstrate the viral origin of the filaments. Suitable virological and serological techniques were used to detect and isolate infectious agents from peripheral blood samples and body excretions of 12 monosymptomatic ON patients at their first acute attack. Nevertheless, any efforts to demonstrate the presence of a virus in these patients have been unsuccessful: no evidence of active viral infection was obtained by serological studies of serum and cerebrospinal fluid samples, nor could viral antigens or inclusions be observed by immunofluorescence and cytochemical analysis. Negative results were also obtained from studies performed in parallel on MS patients and various controls. The significance of the failure to isolate infectious agents from either ON and MS patients is discussed.


Internal calcium concentration and potassium permeability in Paramecium. Ca or EGTA was ionophoretically injected into Paramecium tetraurelia to change [Ca]i. Ca decreased the resting membrane resistance and hyperpolarized the membrane. EGTA had the opposite effect. EGTA following TEA, which suppress GK, had little effect on resistance or resting potential. The I-V relation at steady state was studied before and after EGTA injection while the cell bathed in either K- or TEA-solution. The response to inward test pulses after EGTA injection was similar to that after TEA injection. These results show that [Ca]i controls a steady-state K permeability in Paramecium tetraurelia. A prolonged Ca-spike was recorded after EGTA injection. The plateau potentials in various Ca concentrations in a TEA-solution show the Nernst slope (29 mV for tenfold change in [Ca]o). This result suggests that the prolonged depolarization in this condition is due to a Ca current, after suppression of K-permeability and when [Ca]i is low. The difficulty of obtaining quantitative data on the internal Ca, and the difference between the effects of EGTA injection and TEA injection are discussed.


The personal factor in the maturation of epileptogenic brain scars: review and hypothesis. Does a metabolic factor, variable but personal to the individual, determine the interval between a brain injury and the onset of late traumatic epilepsy? It could account for the unpredictability of this maturation period, and for the fact that only about 50% of brain scars give rise to epilepsy at all.


Morphological study of skin biopsy specimens: a contribution to the diagnosis of metabolic disorders with involvement of the nervous system. Skin biopsies were performed in 71 patients affected by the following disorders: ceroid-lipofuscinoses (17 cases), mucopolysaccharidoses (13 cases) mucolipidoses (seven cases), lipidoses (18 cases), metabolic diseases to be further classified (seven cases), acid maltase deficiency (nine cases). After a survey of semithin sections, the skin specimens were examined with the electron microscope. In most of the cases, epithelial cells, hair follicles, fibroblasts, eccrine sweat glands, smooth muscle cells, sebaceous glands, and nerve bundles were available. In 62 cases (87.3%), positive diagnostic information was obtained while in seven other cases (9.9%) suggestive features were discovered which could support the final diagnosis. In only two cases (2.8%) were the results negative. We conclude that, in association with enzymatic assays in the cultured fibroblasts, a skin biopsy specimen provides a simple opportunity for the combination of both morphological and biochemical diagnosis of storage disorders, precluding major surgical procedures.


Effect of atropine on cerebrovascular responsiveness to carbon dioxide. Effects of cholinergic inhibition by atropine on cerebral circulation were studied in 15 baboons anesthetized with sodium pentobarbital. Intravertebral infusion of atropine, 0.1 mg/kg, did not cause any changes in cerebral blood flow (CBF), superior sagittal sinus wedge pressure (SSWP), epidural pressure (EDP), cerebral perfusion pressure, or cerebral vascular resistance under normal conditions. Cerebrovascular responsiveness to carbon dioxide (CO2) inhalation was not influenced by atropine. The presence of cholinergic nerve fibers has been proved in the cerebral blood vessels and the existence of cholinergic mechanism suggested in the brain stem, but it is not likely that the cholinergic nerves have tonic control of cerebral blood vessels in the resting state or affect cerebrovascular responsiveness to CO2. The changes in EDP and those in SSWP showed a very good correlation to each other. There was also a good correlation between the changes in CBF and those in EDP or SSWP.


Pharmacokinetics of intracarotid artery 14C-BCNU in the squirrel monkey. A comparison of intravenous to intracarotid artery (ICA) administration of 14C-BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) was made in squirrel monkeys. Radioactivity was measured as soluble drug products and as RNA-, DNA-, and protein-bound radioactivity. The ICA administration of BCNU achieved 190% to 280% higher brain nucleic acid-bound drug levels than use of the intravenous route in the infused hemisphere and 130% to 280% higher levels than in the noninfused hemisphere. In addition, some brain regions directly subserved by the middle cerebral artery had bound drug levels four- to fivefold greater than those found in regions of noninfused brain. The data suggest that a need for BCNU dose reduction due to myelotoxicity may be an indication for ICA therapy in selected brain-tumour cases.


The effect of intracarotid infusion of dexamethasone and 5-hydroxytryptamine on cerebral blood flow and metabolism in baboons. The effect of intracarotid infusion of dexamethasone on cerebral blood flow and cerebral oxygen utilization was measured in baboons using the xenon-133 clearance technique. The cerebrovascular response to intracarotid infusion of 5-hydroxytryptamine (5-ht) was then determined during simultaneous infusion of the steroid. Infusion of dexamethasone alone and infusion with 5-HT produced no significant change in cerebral blood flow or cerebral oxygen utilization when compared to baseline values. The study indicates that neither dexamethasone nor 5-HT with dexamethasone modify cerebral blood flow when infused via the internal carotid artery.


Effect of NTA and EDTA on calcium metabolism of chickens and Coturnix. Five experiments were conducted in which various levels of nitrilotriacetic acid (NTA or its salt, Na2NTA) disodium ethylenediaminetetraacetic acid (Na2EDTA) and calcium (Ca) were fed to young chicks, young quail and adult quail. The duration of trials was from 1 to 28 days of age for chicks, 7 to 49 for young quail and 167 to 210 for adult quail. Feeding 0.71% NTA or an equimolar level of Na2NTA caused a moderate decrease in chicks weight and Na2EDTA caused a drastic decrease in body weight of chicks and adult quail. Feeding Na2EDTA caused greater mortality in chicks receiving a low Ca diet than a higher level of Ca. Plasma Ca levels were significantly increased by NTA in young quail and by Na2NTA in adult quail, in contrast, they were significantly decreased by Na2EDTA in adult quail. Dietary NTA promoted greater tibia mineralization (ash/dry matter) in growing chicks. Dietary NTA increased the deposition of zinc (Zn) and manganese (Mn) in the chicks tibia, but, it decreased magnesium (Mg). On the other hand, Na2EDTA caused a significant decrease in Zn and Fe in the chicks tibia and a significant increase in Mn. Coturnix are less sensitive than chickens in responding to dietary chelates.


A new form of nucleoside phosphorylase deficiency in two brothers with defective T-cell function. Two brothers, age 9 and 11, respectively, have marked deficiency of nucleoside phosphorylase associated with defective T-cell function and normal B-cell function. Unlike the previously described five patients with this syndrome, each of these children has sufficient NP catalytic activity in their red blood cells (below 1% of the normal level) to be visualized after electrophoresis and staining for the enzyme. Their healthy sibling has normal NP activity and a normal isozyme pattern. The nonconsanguineous parents have about half-normal NP activity, but their electrophoretic patterns differ from each other's and from those of their affected children. These findings are consistent with genetic heterogeneity at the NP structural gene locus, resulting in compound heterozygosity for two different abnormal alleles.


Impaired defense against vaccinia in a child with T-lymphocyte deficiency associated with inosine phosphorylase defect. A case of progressive vaccinia associated with a profound deficiency of cellular immunity and a defect in inosine phosphorylase is described. A striking contrast was observed between humoral immunity, which showed little if any impairment, and a severe cellular defect affecting both markers and functions of T lymphocytes. The child died despite treatment with methosazone, levamisole, transfer factor, irradiated blood transfusions, and a thymus graft. An adequate serum level of antibody to vaccinia virus was obtained by transfer of specific immunoglobulins, but this failed to stop the progression of the disease. This observation suggests that host defense against vaccinia infection is mainly mediated by cellular immunity.


Inherited human collagen lysyl hydroxylase deficiency: ascorbic acid response. A patient is described with congenital hypotonia, lax joints, friable skin, hemorrhagic scars, high-arched palate, and borderline microcornea. Acid hydrolyzed whole skin collagen had a reduced hydroxylysine content of 0.5 residues per 1,000 as compared to 5.1 +/- 0.7 in control skin. Collagen lysyl hydroxylase in dialyzed subcellular fractions of cultured skin fibroblasts required L-ascorbate as a principal cofactor. Activity of this enzyme in cultured skin fibroblasts derived from this patient, his father, and mother were 17%, 66%, and 39% of control values, respectively. Collagen prolyl hydroxylase activity was normal. Pharmacologic amounts of oral vitamin C (4 gm/day) produced an increase and withdrawal resulted in abrupt diminution of urinary excretion of hydroxylysine. Over a two-year period the patient's wound healing and muscle strength improved and corneal diameter increased. Hydroxylysine content of the skin did not increase.


Idiopathic infantile arterial calcification in siblings: radiologic diagnosis and successful treatment. Idiopathic infantile arterial calcification is a disorder of unknown etiology manifested by widespread arterial calcification. This usually leads to early death from coronary artery occlusion. In 12 of the 75 cases in the literature, radiographs were taken and it was possible to make the diagnosis in them all. We present two patients, siblings, in whom the diagnosis was established radiologically. The nature of the calcium deposits was studied in one of the infants and proved to be calcium hydroxyapatite. Therapy with diphosphonate was apparently successful in the other child.


Morphologic analysis of the pulmonary vascular bed in infants exposed in utero to prostaglandin synthetase inhibitors. Since the effects of prostaglandin synthetase inhibitors on the developing human fetal pulmonary vasculature are unknown, we studied the lungs of two infants, one whose mother took salicylates and the other whose mother took indomethacin during pregnancy. Lungs were fixed by perfusion and fifth generation (resistance) vessels identified. The infant with chronic exposure to aspirin had premature constriction of the ductus arteriosus, tricuspid insufficiency, increased pulmonary arterial medial width/external diameter ratio due to increased smooth muscle, and a decreased number of pulmonary vessels/cm2 lung tissue. The infant with short-term exposure to indomethacin had hypoxemia, increased pulmonary arterial m/d ratio due to increased smooth muscle, and a normal number of pulmonary vessels/cm2 lung tissue. These abnormalities may be due to the effects of prostaglandin synthetase inhibitor drugs on the ductus arteriosus and/or the pulmonary vessels of the human fetus.


Immunologic aspects of human colostrum and milk. I. Distribution characteristics and concentrations of immunoglobulins at different times after the onset of lactation. Human colostrum and milk collected at different times after the onset of lactation from 200 subjects were tested for the levels of IgG, IgA, and IgM classes of immunoglobulins. The technique of radial immunodiffusion was employed. The levels of IgG immunoglobulin ranged from 1.4 to 4.9 mg/gm of protein at different intervals after onset of lactation. No significant change was observed in the individual levels of IgG over 180 days of sequential testing. On the other hand, highest levels of IgM and IgA immunoglobulins in the colostrum and milk were observed during the first three to four days postpartum. The IgM levels ranged from 27 to 30 mg/gm protein and IgA levels, from 22 to 35 mg/gm protein. A 3- to 4-fold decline in the levels of IgM and IgA immunoglobulin was demonstrated in milk samples collected 15 to 180 days postpartum. These observations provide reference data on the levels of immunoglobulins in colostrum and milk at different stages of lactation.


Essential fatty acid deficiency in neonates: inability to reverse deficiency by topical applications of EFA-rich oil. Correction of essential fatty acid deficiency by transcutaneous absorption of topically applied EFA-rich oil has been reported. We measured serum EFA levels in two groups of neonates receiving fat-free total parenteral nutrition: nine control patients after 16 and 25 days of TPN, and six patients before and 12 days after beginning cutaneous application of 100 mg/kg/day of linoleic acid as sunflower seed oil. Progressive biochemical EFA deficiency occurred in all but one of the control patients. Of the six patients receiving 100 mg/kg/day of linoleic acid, one patient with mild deficiency improved, but progressive EFA deficiency occurred in the other five patients. Serum EFA levels were also measured in four patients following 76 days of TPN and daily application of high doses of topical safflower oil, all of whom had severe biochemical EFA deficiency. The topical application of EFA-rich oil cannot be assumed to be uniformly effective in reversing or preventing EFA deficiency. The transcutaneous absorption of essential fatty acids must be documented by appropriate measurements of EFA in serum lipids.


Peripheral total parenteral nutrition for premature infants with the respiratory distress syndrome: a controlled study. In 40 premature infants, in whom severe respiratory distress precluded oral feeding, peripheral total parenteral nutrition consisting of casein hydrosylate, dextrose, and soybean emulsion was compared to nutrition with dextrose and electrolytes. The TPN group received more calories, and the total serum protein in them increased significantly. Metabolic complications did not occur. Transient thrombocytosis occurred in six infants who received TPN and eosinophilia occurred in nine. The case fatality rate in the TPN group (three of 20) was not significantly less than in the glucose group (six of 20). The differences suggested that infants who weigh less than 1,500 gm may receive the greater benefit from TPN.


Enterocutaneous fistulas of the small bowel in children (25 cases). During the past 5 yr, 25 children ranging in age from 10 days to 14 yr have been treated for single or multiple severe enterocutaneous fistulas. There were two deaths. In 24 cases out of 25, initial treatment was nonsurgical and consisted of nutritional support (by total parenteral nutrition in 20, and constant rate enteral feeding in 4) and was associated with local treatment. Successful closure was achieved without surgery in 13 cases, and 11 secondary operations were performed, with success in 9. The addition of nutritional methods has completely changed the prognosis of enterocutaneous fistula.


Zinc deficiency during total parenteral nutrition in childhood. Changes in plasma zinc levels were studied in 11 pediatric surgical patients treated with total parenteral nutrition. Plasma copper levels were also determined in some patients. In three patients plasma zinc fell to a very low level during long-term total parenteral nutrition, and a syndrome of zinc deficiency developed characterized by dermatitis, alpecia, and enterocolitis with striking response to intravenous zinc therapy. In contrast, plasma zinc levels in the patients with short-term total parenteral nutrition remained in the normal range during the present study. This suggests that one of the mechanisms of zinc deficiency during total parenteral nutrition is insufficient amount of zinc in the nutritional solutions for long-term use, especially for older children. Symptoms of the zinc deficiency also occurred in these patients during the anabolic phase, suggesting that tissue demand for zinc may be increased at that time. Therefore, zinc should be included, on a regular basis, in all parenteral nutritional solutions in amounts sufficient to meet estimated needs for growth and tissue repair.


The reinforcing properties of procaine and d-amphetamine compared in rhesus monkeys. Twelve rhesus monkeys were studied under a fixed-ratio (FR) schedule of intravenous procaine or d-amphetamine injection from 8 A.M. to 4 P.M. daily. Under the FR schedule, every nth lever press produced an injection. The FR value (n) and the dose per injection of procaine and d-amphetamine were varied systematically. At a FR value of 10, responding was maintained by doses of procaine ranging from 0.125 to 12 mg/kg/injection and by doses of d-amphetamine ranging from 0.01 to 0.1 mg/kg/injection. At doses of 1 mg/kg/injection of procaine and 0.1 mg/kg/injection of d-amphetamine, responding was maintained at FR values up to 100 by procaine and d-amphetamine but not by saline. Responding and drug intake were relatively constant throughout each 8-hour session with procaine, but responding tended to decrease and was more variable over the session with d-amphetamine. No toxic effects were observed in doses up to 6 mg/kg/injection with procaine. At this dose, eating and drinking ceased during the period of access to the drug. One of the four monkeys died at 8 mg/kg/injection of procaine. At 12 mg/kg/injection all three monkeys tested showed signs of toxicity.


Calcium ion requirement for acetylcholine-stimulated breakdown of triphosphoinositide in rabbit iris smooth muscle. Previous studies from this laboratory have established that addition of acetylcholine (ACh) or norepinephrine to 32P-labeled rabbit iris smooth muscle increases significantly the breakdown of triphosphoinositide (TPI) and that these stimulatory effects are blocked by atropine and phentolamine, respectively. The present studies were undertaken in order to show the effect of Ca++ on the ACh-stimulated breakdown of TPI ("TPI effect") in this tissue. Paired iris smooth muscles were prelabeled with 32Pi for 30 minutes at 37 degrees C in Ca++-free iso-osmotic salt medium. The prelabeled irises were then washed and incubated for 10 minutes in nonradioactive Ca++-free medium which contained 10 mM 2-deoxyglucose under various conditions. The phospholipids were isolated by means of two-dimensional thin-layer chromatography and their radioactivities were determined. In the absence of Ca++, 50 micrometer ACh increased TPI breakdown and phosphatidic acid (PA) labeling by 16 and 38%, respectively. In the absence of ACh, 0.75 micrometer Ca++ increased TPI breakdown and PA labeling by 11 and 20%, respectively. When both ACh and Ca++ were added, the increase in TPI breakdown and PA labeling rose to 32 and 74%, respectively. The labeling of phosphatidylinositol was found to be insensitive to the presence of Ca++. Ca++ was determined in the iris smooth muscle and it was found to contain 3.13 mumol of Ca++ per g of tissue. This was reduced by 80% after the muscle was washed and incubated in a medium which contained 0.25 micrometer ethyleneglycol bis (beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA). The TPI effect was abolished by 0.25 micrometer EGTA and restored when excess Ca++ (1.25 micrometer) was added. Concentrations of Ca++ as low as 50 micrometer provoked a TPI effect. Sr++ (2 micrometer), but not Ba++ or Mn++, was found to substitute partially for Ca++. Ionophore A-23187 (20 micrometer) was found to increase the breakdown of TPI and labeling of PA by 11 and 24%, respectively. High concentrations of Ca++ (20 mM) exerted similar effects. The increase in TPI breakdown and PA labeling in response to these agents, in contrast to the TPI effect in response to ACh, was not blocked by atropine. This suggests that the observed effects are not caused by the release of endogenous ACh from the muscle. A possible interpretation for the above observations on the role of Ca++ in the TPI effect at the postsynaptic membrane of the iris smooth muscle could be: (formula: see text).


EGTA and motoneuronal after-potentials.

EGTA and motoneuronal after-potentials. 1. Intracellular iontophoretic injections of EGTA (5--20 nA) into cat spinal motoneurones consistently greatly reduce the amplitude of the delayed after hyperpolarization (a.h.p.) that follows the spike. 2. This effect is accompanied by a large reduction (on average by 3/4) in the marked increase in input conductance normally associated with the a.h.p. 3. There is also a consistent, though less regular, tendency for the resting input conductance to decrease (on average by 1/5), as well as some depolarization. 4. Recovery of the a.h.p., the associated conductance increase and the resting conductance is ver slow. It is sometimes accelerated by injections of citrate and Cl-, or CA2+. 5. Other hyperpolarizing phenomena, such as recurrent or othodromically-evoked i.p.s.p.s, are not depressed by injections of EGTA. 6. When depolarization is minimal EGTA injections that markedly depress the a.h.p. do not affect the rate of rise or fall of the spike. If, as a result of depolarization, an early a.h.p. is visible, it is patently insensitive to EGTA. 7. The post-spike depolarizing after-potential (delayed depolarization) is not obviously affected by EGTA, apart from the usual diminution seen during depolarization. 8. Since the main action of EGTA is to bind free Ca2+, the marked depression of the a.h.p. indicates that the sharp increase in K conductance which generates the a.h.p. is probably caused by a influx of Ca2+ accompanying the action potential. It is suggested that this inward Ca2+ current may be manifested in the depolarizing after-potential.


Significance of 2,4-dinitrophenol action on spinal motoneurones. 1. Extracellular iontophoretic applications of DNP lead to an increase in the membrane conductance of cat spinal motoneurones, manifested by a rise in input conductance, a slower rate of rise and fall of action potentials, and occlusion of the afterhyperpolarization. 2. There is also some hyperpolarization, but the reversal potential for the action of DNP is only about 12 mV more negative than the resting potential. 3. These effect of DNP can be abolished or significantly reduced by intracellular injections of EGTA. On the other hand, DNP can partly reverse the decreased conductance and the depression of the slow afterhyperpolarization caused by EGTA. 4. Intracellular injections of DNP also induce a rise in input conductance; when repeated, they tend to have a depolarizing effect, mainly irreversible. 5. It is concluded that DNP acts principally inside the motoneurone, by liberating bound internal Ca, the free Ca ions then raising membrane conductance, especially GK.


Actions of EGTA and high calcium on the cones in the turtle retina. 1. The effects of Ca2+ on the activity of retinal cones were investigated by recording intracellular responses from turtle retinae perfused with solutions containing different Ca2+ concentrations. 2. Lowering extracellular Ca2+ concentration with EGTA increased membrane conductance and evoked depolarization in darkness. 3. Responses to bright lights were increased by EGTA by an amount equal to the depolarization in darkness; responses to dim lights instead were usually reduced. In addition EGTA modified the time course of responses to flashes. These changes were especially evident during the later phases of the response. 4. A steady light applied during EGTA perfusion can restore the original membrane potential. The kinetics of responses in these conditions, however, differ profoundly from those prevailing Ca2+ concentrations evoked hyperpolarization of the cones and decreased the amplitude of their responses to bright lights. The time course of responses to flashes was not appreciably modified by high Ca2+. 6. A steady light which hyperpolarizes the cone membrane by the same amount as high Ca2+ has an equal effect on the amplitude of responses to bright flashes but has an entirely different action on response kinetics and on the amplitude of responses to dimmer flashes. 7. The effects of EGTA on resting potential, conductance and response amplitudecan be interpreted assuming that the drug opens channels which are normally closed by Ca2+ in darkness. Conversely, the changes caused by high Ca2+ suggest that raising the concentration of outside Ca2+ reduces the number of light-sensitive channels open in darkness. 8. The observation that Ca2+ and light have different effects on kinetics and sensitivities is difficult to reconcile with the hypothesis that Ca2+ is the substance liberated by light to cause photoresponses.


Effect of 1-(2,4-dichlorobenzyl)-indazole-3-carboxylic acid on sperm tails in rhesus monkeys. Large numbers of spermatozoa with bent or coiled tails were found in the ejaculates of rhesus monkeys treated with 1-(2,4-dichlorobenzyl-indazole-3-carboxylic acid (DICA) (50 or 500 mg/kg for various periods). The defect appeared only in spermatozoa in the cauda epididymidis and consisted of axoneme disarrangement and loss of the fibre doublets. The coil was completely enclosed in a membrane.


Prolactin response to synthetic TRF in pregnant ewes. The prolactin secretion response to TRF was similar at all stages of pregnancy (Days 40, 66, 102 and term).


Pituitary responsiveness to LH-RH and TRH and the effects of progesterone or progesterone and oestradiol treatment in anoestrous sheep. Pituitary responsiveness to 200 microgram synthetic LH-RH and to 10 microgram TRH was determined in anoestrous sheep before and after treatment for 3 weeks with progesterone (100 mg/day), or oestradiol (250 microgram/day) plus progesterone (100 mg/day). There was a marked decrease in pituitary responsiveness to LH-RH after progesterone (P is less than 0.01), or oestradiol plus progesterone (P is less than 0.01) treatments, and an increase in response to TRH after oestradiol plus progesterone (P is less than 0.01) treatment. The results demonstrate selective and simultaneous feedback effects of oestradiol and progesterone on pituitary responsiveness to two hypothalamic releasing hormones.


E1k, another quantitative variant at cholinesterase locus 1. Two families segregating for the atypical (E1a) allele at cholinesterase locus 1 are described. Unusual results for dibucaine inhibition led to the recognition of a new allele (E1k) also segregating in these families. The enzymatic and immunological data are consistent with the hypothesis that E1k causes reduction of 'usual' (E1u) molecules by about 33%. Whether the reduction of E1u caused by E1k is caused by retarded synthesis or accelerated degradation of serum cholinesterase remains to be determined.


The Axenfeld syndrome and the Rieger syndrome. A family is reported in which both the syndrome of Axenfeld and the eye malformations of the syndrome of Rieger occur, indicating that both may be expressions of the same gene. We also review the associated anomalies already reported, emphasise their high incidence, suggest that these are not accidental associations, and propose some possible explanations for the high incidence.


Medical students' orientation toward the chronically ill. Medical students receive little training specifically directed toward care of chronically ill persons, and physicians, therefore, tend to have little knowledge of alternative long-term care arrangements. Moreover, the negative attitudes toward chronic patients which were observed by Becker in the 1950s still seem prevalent among medical students. Little interest is expressed by medical students in fields which focus on the chronically ill or aged. Restructuring of medical education is necessary in order to promote more concern among physicians with the needs of the chronically ill.


Radiographic diagnosis of choanal atresia induced prenatally with triamcinolone in the baboon (Papio cynocephalus). Choanal atresia was diagnosed radiographically using a water soluble contrast media in 2 of 7 Papio cynocephalus exposed to triamcinolone acetonide in utero. In one P. cynocephalus, the atresia was complete and was associated with other orofacial abnormalities. The other animal, previously considered to be normal, had a partial nasal obstruction. The radiographic appearance of the drug-induced defects observed in the baboon closely resemble the descriptions of spontaneously occurring defects in human infants.


Response of baboon peripheral blood lymphocytes to phytohemagglutinin: time-course and dose-response relationships. Optimal conditions for studying phytohemagglutinin(PHA)-induced transformation of baboon peripheral blood lymphocytes were determined. Maximal stimulation, as determined by uptake and incorporation of tritiated thymidine (total cell and trichloroacetic-acid-precipitable radioactivity), occurred at a PHA level of 12.5 microgram in a culture volume of 0.25 ml containing 2 x 10(5) lymphocytes. Optimal stimulation occurred after a total incubation period of 114 h, the last 18 h of which was in the presence of 1muCi of the labeled DNA precursor per culture. While there was considerable variation in the extent of responsiveness of lymphocytes from individual animals, the shape of the dose-response and time-course curves for most mitogen concentrations was generally similar.


Effect of chronic oral methadone treatment on the growth of maturing monkeys. Three male rhesus monkeys drank methadone hydrochloride (1.0-2.5 mg/kg/day) in Tang orange drink from age two to four years. Their rate of body weight gain was faster than that found by other experimenters. In a second study one male monkey drank 2.0 mg/kg/day methadone while two others drank only Tang from age 21/2 to 31/2 years. The rate of body weight gain was identical for the three monkeys, and was the same as that found in the previous study. The apparent augmentation of body weight gain in the first study was probably due to inter-laboratory differences in housing and feeding conditions.


Ribosomal RNA homologies and the evolution of the filamentous blue-green bacteria. Ribosomal RNA (rRNA) sequence homology (as determined by comparisons of T1 oligonucleotide catalogs of 32P-labeled 16S rRNAs) has been used to assess phylogenetic relationships within the filamentous and unicellular blue-green bacteria, and to identify regions of evolutionary conservatism within blue-green bacterial 16S rRNAs. Nostoc and Fishcherella, representatives of two morphologically distinct and highly differentiated orders, are shown to be as closely related (on the basis of RNA sequence homology) as typical members of the non-blue-green bacterial genus Bacillus. They are further shown to be (on the same basis) indistinguishable from typical unicellular members of a subgroup of the unicellular blue-green bacterial order Chroococcales. These results have general implications for studies of the origin of differentiated prokaryotes and of evolutionary change in prokaryotic macromolecules. In particular, they provide indirect evidence that the divergences of contemporary major prokaryotic groups are truly ancient ones.


Carcinogenesis induced by 7,12-dimethylbenz[a]anthracene in c3H-A vyfB mice: influence of different dietary fats. The effect of a diet containing either sunflower-seed oil (polyunsaturated fat diet) or tallow (saturated fat diet) on 7,12-dimethylbenz[a]anthracene (DMBA)-induced carcinogenesis in C3H-A vyfB mice was examined. After receiving either diet for 28 days, some of the mice were given an intragastric dose of 5 mg DMBA. To identify the stage of carcinogenesis that might be influenced by dietary fat, the diets of half of the mice were then interchanged so that those previously fed the saturated fat diet were fed the polyunsaturated fat diet and vice versa. The cumulative incidence of tumor-bearing mice was significantly greater among the females fed the polyunsaturated fat diet compared to those fed the saturated fat diet. This enhancement of carcinogenesis was observed only when the mice were fed the polyunsaturated fat diet after DMBA administration. Similar trends were observed in the male mice, but these mice developed fewer tumors and none of the differences between the tumor incidences were statistically significant. The most common sites for tumors in the male mice were the liver, lungs, and skin, whereas those for tumors in the females were the mammary glands and ovaries. The differences in tumor incidence suggest that carcinogenesis was enhanced by the polyunsaturated fat diet during the promotion stage of carcinogenesis.


Comparison of acute response to polychlorinated biphenyl in liver of rat and channel catfish: a biochemical and morphological study. The acute response of liver of channel catfish and rat to polychlorinated biphenyl was compared on a structural and functional basis. Both the rat and the fish had elevated microsomal enzyme activities. However, in the rat the response was quantitatively greater in all respects. Morphologically, rats responded with lipid accumulation and marked increases in smooth endoplasmic reticulum. Fish liver showed lipid accumulation and increased profiles of rough endoplasmic reticulum with alterations in arrangement that appeared as vesicles and parallel cisternae. Minimal changes were seen in smooth endoplasmic reticulum, which appeared to be increased as discrete foci.


Measurement of dietary cadmium absorption in humans. Total body counting was used to determine cadmium absorption in 14 healthy subjects and in 1 patient with an ileostomy. Breakfast was extrinsically tagged with 115mCdCl2, and a poorly absorbed marker, 51CrCl3, was added to determine the point of complete elimination of unabsorbed radiocadmium from the gastrointestinal tract. The 51Cr was not an ideal marker: fecal excretion of radiocadmium continued beyond the point at which chromium was completely eliminated from the body, Nevertheless, it was helpful in six subjects in identifying the presence of unabsorbed radiocadmium still in transit in the lumen of the gastrointestinal tract 3--5 wk after the test meal. The average body retention of radiocadmium determined between 7 and 14 d after the disappearance of the chromium marker from the body was 4.6 +/- 4.0% (SD), with a range of 0.7--15.6%. The biological half-time of absorbed radiocadmium in one of the subjects was 100 d.


Leucocytozoonosis in Canada geese in upper Michigan,. 1. Strain differences among geese from different localities. Geographic variation in pathogenicity of Leucocytozoon simondi in Canada geese (Branta canadensis maxima) was investigated by exposing goslings to natural infection at three locations in the upper peninsula of Michigan. Examination of blood smears and tissue sections revealed two patterns of development. Hepatic schizogony and secondary megaloschizogony occurred in cells of the reticuloendothelial system, with round and elongate gametocytes, or only hepatic schizonts and round gametocytes. The evidence for strain differences in L. simondi and its implications in wildfowl management practices are discussed.


Brucellosis in elk I. Serologic and bacteriologic survey in Wyoming. Incidence of brucellosis in elk (Cervus canadensis) on two winter feedgrounds in Wyoming was examined over a 5-year period by testing serum samples using the standard plate agglutination (SPT) buffered Brucella antigen (BBA), rivanol (Riv) and complement fixation (CFT) tests. Thirty-one percent of 1,165 elk were positive by defined criteria. Considering each test individually, only 29% (106) of 370 positive sera would have been classified as reactors by the SPT, 83% (307) by the BBA test and 86% (314) by the Riv test. The CFT would have identified 85% (267) of 332 positive samples on which it was used. Brucella abortus, type 1, was isolated from 17 of 45 elk necropsied. The SPT identified 59% (10) of these as reactors, the BBA test 94% (16) and the Riv test 88% (15). The CFT identified nine of nine (100%) on which it was used. Prevalence of sero-positive animals increased with age. Brucellosis has been present in one of the two elk herds since at least 1930, and the incidence of infection among mature females in both herds was approximately 50% during this study. No single serologic test should be relied upon to diagnose brucellosis in elk.


Ampicillin therapy for pharyngeal gonorrhea. Single-dose oral ampicillin trihydrate is ineffective for the treatment of pharyngeal gonorrhea. An evaluation was made of the efficacy of extended oral ampicillin therapy. The regimen consisted of a single oral 3.5-g dose of ampicillin trihydrate and 1.0 g of probenecid on the first day, followed by 500 mg of ampicillin tridhydrate four times a day for each of the succeeding two days, for a total ampicillin trihydrate dose of 7.5 g. One or two follow-up cultures taken within 35 days of completion of therapy were obtained in 77 of the 101 patients treated. Positive test-of-cure cultures were reported in three persons, two of whom may have been reinfected. The failure rate was calculated to range between 1.3% (1/77) to 3.9% (3/77). This compares favorably with current recommended modes of therapy.


Some host defence factors in iron deficiency anemia. Nitroblue tetrazolium (NBT) dye test, Dinitrochlorobenzene (DNCB) contact sensitization reaction, and purified protein derivative (PPD) skin test were carried out in a group of 80 women. The results showed a significant depression in all the three tests in cases who were anemic.


Rosette forming T lymphocytes in healthy subjects and patients with liver disease. The number of rosette forming T cells was significantly reduced in patients with acute viral hepatitis, cirrhosis of the liver and liver cancer. The frequency of T cells in various hepatic disorders correlated well with the impairment of delayed hypersensitivity response to DNCB.


Serum immunoglobulin and transferin in preschool children. Considerable variation was observed in immunoglobulins, estimated in 75 preschool children. The mean +/- 1 SD levels of IgG, IgM and IgA were found to be 1241 mgs% +/- 366, 149 mgs% +/- 48,231 mgs% +/- 99 respectively. A significant correlation of serum albumin was found with transferin and hemoglobin, but none existed between hemoglobin and transferin.


Immunoglobulins in healthy subjects and blood donors. Levels of immunoglobulins in serum were determined in 41 healthy subjects and 128 professional blood donors. In healthy subjects mean levels +/- S.D. were: IgG 1260 +/- 492.9 mg/dl, IgM 62.4 +/- 18.2 mg/dl, and IgA 183.4 +/- 70.1 mg/dl. Of 128 blood donors 112 were hepatitis Bs antigen (HBsAg) negative and 16 were positive. A significant (P is less than 0.001) elevation of all three immunoglobulins was observed in HBsAg positive group suggesting increased antibody formation due to persistance of antigen.


Immunoglobulins in liver disease.

Immunoglobulins in liver disease. Serum immunoglobulins were determined in 39 healthy subjects and 55 patients with a variety of acute and chronic liver diseases. Elevation of IgG and IgA was frequently observed in healthy subjects and patients with acute viral hepatitis, liver cancer and miscellaneous liver disorders. IgG and IgM were elevated in cirrhosis of the liver.


Heterogeneity of amylase in diabetes mellitus. Serum amylase, total reducing capacity, true glucose and saccharoid fractions were determined in healthy subjects and patients with diabetes mellitus. An increase in the enzyme activity was observed in patients with diabetes mellitus and further elevation occurred with increase in the age. An increase in the activity of isoenzymes was also observed.


Effects of elastase, protease and common antigen (OEP) from Pseudomonas aeruginosa on protection against burns in mice. For the purpose of studying the role of elastase and protease of Pseudomonas aeruginosa in bacterial infection in burns, the effects of the vaccines made from each enzyme, their toxoids and OEP on protection against infection in burned mice were studied. Elastase, protease, toxoids of the enzymes, two- or three-component-mixed vaccines and OEP demonstrated significant protection. Toxoids of elastase and protease produced effects similar to those of the enzymes themselves but no synergistic effect in mixed vaccine was detected. Elastase was significantly more effective than protease, the three-component-mixed vaccine or OEP in protecting mice against P. aeruginosa infection in burns.


[Treatment of band keratopathy with EDTA (author's transl)]. Six eyes with band keratopathy were treated with ethylenediamintetraacetacid (EDTA). The treatment is simple, shows no harmful complications and may replace corneal grafting. EDTA treatment can not be successful if a pannus or hyalin deposits impede contact between EDTA and the calcium deposition. Histopathologic examination suggests that the basement membrane of the corneal epithelium is the primary focus of cristallisation of the calcium salt. Even in long standing cases of band keratopathy only the most superficial layers of the cornea are involved.


Acepromazine-ketamine anesthesia in the rhesus monkey (Macaca mulatta). Six adult male rhesus monkeys (Macaca mulatta) were anesthetized using a combination of acepromazine maleate and ketamine hydrochloride administered by intramuscular injection. This combination produced a smooth induction to anesthesia requiring less than 5 minutes. The average duration of anesthesia was slightly less than 1 hour and was safely prolonged with additional doses of ketamine. The depth of anesthesia was sufficient for minor surgical procedures and for precise radiological studies. No deleterious side effects were noted, and animals recovered completely in a short time.


Sex determination in the common marmoset (Callithrix jacchus). The general morphology of the external genitalia was examined in 43 common marmosets (Callithrix jacchus) ranging in age from newborn to adult. At birth, the scrotum was a small irregular fold of skin on either side of the caudal aspect of the penis. The testes were not present in the scrotum until 8--11 months of age. The scrotum covered the penis in the adult male, was devoid of fur, was covered by pearly while nodules, and presented a median raphe. In the young female, the pudendal pad closely resembled the scrotum of the male. The vulva was pendulous, and the small vestibular opening was located near its most ventral aspect and closely resembled the preputial opening of the male. In the adult female, the pudendal pad was pendulous, was studded with white nodules, and closely resembled the scrotum of the male. Sex determination by casual observation resulted in numerous errors. Accurate sex determination was based on differences in the preputial and vestibular openings, demonstration of the glans penis in the prepuce, and palpation of the testes in the scrotum or inguinal region.


Placenta extrachorialis in the stumptailed macaque (Macaca arctoides). Placenta extrachorialis was diagnosed in two of 56 placentas obtained from stumtailed macaques (Macaca arctoides) after elective cesarean section. The condition was characterized by the presence of an annular ring of necrotic tissue and fibrin at the margin of the villous chorion. Because these cases occurred in two of six known primiparous females, it was suggested that thte condition may account, at least in part, for the high incidence of pregnancy-related problems observed in primiparous stumptailed macaques.


Bacterial endocarditis with obstruction of the right atrioventricular orifice and the pulmonary outflow trace in an African monkey (Cercopithecus aethiops). A 7 to 8-year-old male African green monkey (Cercopithecus aethiops) was found moribund in his cage. Fluid and antibiotic therapy were administered, but the monkey dies 2 hours later. At necropsy, large septic mural thrombi obstructed the right atrioventricular orifice and the pulmonary outflow tract, and smaller septic thrombi were attached to the leaflets of the pulmonary and mitral valves. Staphylococci were isolated from the large thrombus occluding the atrioventricular orifice. Large abscesses were present in the upper and lower lobes of the right lung, and small, wedge shaped infarcts were present in the lungs and kidneys. The clinical and pathologic findings were consistent with a rapidly progressive form of bacterial endocarditis. This was the only case of vegetative bacterial endocarditis seen at this instituion in 700 necropsies of nonhuman primates.


Hypothalamo-pituitary-thyroid axis function during cardiopulmonary bypass. Marked alterations in levels of circulating thyroid hormone were found in patients undergoing cardiopulmonary bypass with a rise in the free thyroxine and a fall in the free triiodothyronine levels. Studies using thyrotropin-releasing hormone during bypass demonstrated a blunted response to this stimulus. This reduced response is related to changes in thyroid hormone levels and it is suggested that bypass surgery may have a direct inhibitory action on thyroid-stimulating hormone release at the hypothalamo-pituitary level. The potential significance of these hormonal changes is discussed.


Recovery of group A and nongroup A beta-hemolytic streptococci from throat swab specimens. The recovery of beta-hemolytic streptococci from throat swab specimens, from 1973 through 1975, was analyzed. Group A and nongroup A beta-hemolytic streptococci were recovered from 16.5% and 16.1%, respectively, of the specimens received. Although the recovery of group A streptococci fluctuated during the year, with the greatest incidence during the winter and spring months, the recovery of nongroup A streptococci was constant throughout the year. The proportion of group A to nongroup A streptococci was significantly greater in specimens collected during the winter and spring months than in those collected during the summer and fall months, and in specimens from pediatric patients than in those from adults.


[Complete colonoscopy with short instruments--results obtained with the ACMI F9S (author's transl)]. Total colonoscopy was performed in 3,740 cases within approximately 4 years. Results show, that total colonoscopy may be used as a primary method of clinical examination in an optimal way, if the technically improved, new class of instruments is used. The new short ACMI F6S is especially suited for this approach, yielding reliable results in about 92% of all patients, if the colon is clean and if there are no organic stenoses present.


Influences of exogenous intake and nitrogen balance on plasma and brain aromatic amino acid concentrations. In an effort to determine the sum of the factors influencing the plasma and brain concentrations of aromatic amino acids in rats with liver disease, rats with end-to-side portacaval shunts and their sham-operated controls were placed on various oral and intravenous diets by the techniques of parenteral nutrition. In sham-operated animals with normal hepatic function, the source of amino acids and their composition appeared to play little role in the plasma and brain aromatic amino acids and a derivative of brain tyrosine, octopamine. After end-to-side portacaval shunt, however, plasma and brain concentrations of aromatic amino acids were responsive to exogenous intake in the presence of hepatic impairment. In a group of rats with end-to-side portacaval shunt and presumed hepatic impairment, graded increments of protein equivalent were given with isocaloric hypertonic dextrose by the techniques of parenteral nutrition. When the animals achieved positive nitrogen balance, there were decreased levels in plasma and brain of the aromatic amino acids, phenylalanine and tyrosine, and a derivative of tyrosine, octopamine. A clear statistical relationship between plasma and brain tryptophan and nitrogen balance was not observed. The results suggest that in animals with hepatic impairment secondary to end-to-side portacaval shunt both exogenous intake and the level of catabolism (nitrogen balance) influence plasma and brain aromatic amino acids.


Fasting metabolism in infants. I. Effect of severe undernutrition on energy and protein utilization. Fasting energy metabolism was studied in infants to determine the rates of utilization of endogenous carbohydrate, fat, and protein in relation to length of fasting, glucose homeostasis, other circulating energy substrates and hormones, and severe depletion of energy reserves due to prior malnutrition. Five subjects about 1 yr of age were each studied before and after restoration of their energy reserves. Following 3 days of a standard maintenance intake of energy and protein, the subjects were fasted until glycogen oxidation became negligible. Total energy utilization, determined by hourly oxygen consumption, did not diminish as a result of fasting but was significantly less when malnourished than when recovered, 66 versus 79 kcal/kg/day. In all cases the major energy source shifted from oxidation of dietary carbohydrate and glycogen to oxidation of fat, determined from the respiratory quotient, until the oxidation of glycogen became negligible and fat provided 94% of energy in the malnourished subjects after 21 hr and 92% in the recovered subjects after 27 hr. Utilization of protein, determined from urinary nitrogen excretion, remained very low in the malnourished infants accounting for a maximum of 4% of energy, 103 mg N/kg/day, whereas after recovery, protein utilization doubled as a result of fasting, finally accounting for 7% of energy, 226 mg N/kg/day (p less than 0.005). Urea accounted for 60% of total urinary N in both groups and plasma urea increased correspondingly in the recovered but not in the malnourished subjects. Plasma glucose decreased to about 40 mg/100 ml in both groups as glycogen oxidation diminished. The maximum amount of glucose that could have been derived from dietary carbohydrate, glycogen, glycerol, and amino acids decreased over this time from about 6 to 1 mg/kg/min. Alanine declined in relation to glucose concentration and was not different in the two groups in spite of the difference in urea production. Glycerol free fatty acids, beta-hydroxybutyrate, and acetoacetate increased in both groups, but the latter three of these remained significantly less in the malnourished group. Insulin decreased rapidly and remained equally low in both groups. Urinary epinephrine increased in both groups and cortisol was elevated after fasting, while growth hormone did not increase significantly. It is concluded that fasting infants complete the transition from dietary carbohydrate to endogenous fat as the major energy source much faster than do adults, proportionate to relatively greater energy utilization. Severe wasting did not prevent energy homeostasis in spite of greatly depleted body fat. Oxidation of fat continued to provide virtually all of the fasting energy requirements, although ketosis was relatively less. Utilization of endogenous protein also increased as a result of fasting but, by contrast, provided only a very small fraction of total energy, and this was substantially diminished as a result of wasting, similar to what has been found in starved adults...


Metabolic effects of clofibrate in insulin-dependent ketosis-prone diabetic man. This study examined the effects of clofibrate therapy on basal plasma substrate and hormone concentrations in ketosis-prone insulin-dependent diabetic man. A double-blind crossover design was utilized during a 3-mo period in which clofibrate treatment (1 g b.i.d.) was compared to that of a lactose placebo (1 g b.i.d.). Our results demonstrate that clofibrate treatment resulted in a significant reduction in the concentration of plasma glucose, ketone bodies, free fatty acids, triglyceride, and cholesterol in diabetic man. These beneficial effects were observed without demonstrable changes in circulating concentrations of insulin and glucagon. These observations suggest that in ketosis-prone diabetic man, clofibrate therapy may provide an adjunct to exogenous insulin administration.


Characterisation of Tn501, a transposon determining resistance to mercuric ions. The transposon encoding resistance to mercuric ions, Tn501, is 5.2 (+/-0.1) x 10(6) daltons and is bounded by small inverted repeats. The restriction sites for the restriction endonucleases EcoRI, HindIII and SalGI have been mapped on the element.


Photon and electron response of silicon-diode neutron detectors. The photon response of silicon-diode neutron detectors is analyzed theoretically and measured in the 15-25-MeV region. The main mechanism for producing a response in the diode is shown to be the displacement of silicon atoms by scattering of electrons. If the photon source is an electron accelerator target, the response is mostly due to electrons originating in the target with a smaller contribution from electrons produced in the diode by photons generated at small angles to the beam.


Differences in pattern of a DNA protein complex isolated from vegetative cells and spores of Bacillus subtilis. A DNA protein complex has been isolated from vegetative cells and spores of Bacillus subtilis. Properties of the DNA protein complex prepared from vegetative cells were studied and SDS gel electrophoresis was employed to compare the different DNase-untreated and -treated DNA protein complexes. It is concluded that proteins are associated with the DNA and differences in protein pattern in polyacrylamide gels indicates the involvement of DNA-binding proteins in the regulation of spore formation.


[Dosage effects of the non permissive allele of Drosophila ref(2)P gene on sensitive strains of sigma virus (author's transl)]. Different characteristics of flies relating to sigma virus allow us to class the following drosophila genotypes according to their permissivity for the virus strains which are sensitive to the Pp allele: (formula: see text). It is concluded 1) that the two alleles Po and Pp of ref(2)P gene are active and 2) that the viral protein which interact with the product of ref(2)P is effective, or effectively transformed, without interaction with the product of ref(2)P. The delayed appearance of CO2 sensitivity symptom in flies which are issued from stabilized maternal lines, while they are immune to a superinfection non Pp sensitive virus, leads us to believe that ref(2)P is active not only on a function necessary to viral genome replication, as assumed by preceding workers, but also on a function necessary to maturation for the viral strain which was used.


Two related structural genes coding two homologous serine proteases in the Bacillus subtilis genome. A Bacillus subtilis intracellular serine protease is homologous in sequence to an extracellular serine protease from the same strain, indicating the presence of two related structural genes in the Bacillus subtilis genome.


[Some questions about blood group nomenclature]. Author in introductory part of the paper deals with several basic principles of the scientifical nomenclature, then with the up to date definition of "blood-groups". The so called "blood-groups" in the human and in animals represent biochemical, more exactly structurechemical polymorphisms, i.e. they are genetically regulated inherited variants of some functionally basic molecules. Consequently the expression "blood-groups"--which originally implied Landsteiner's ABO-system and it's groups--nowadays include various types (erythrocyte-membrane, serum, enzym etc.) of structural polymorphisms. Author recommends to sign serum samples ("Serotypes") as anti-A, anti-B and anti-A + B. Definition of "sub-groups" and "variants" is given. Author deals with the nomenclature of Rh-system including Rh-phenotypes and genotypes. At last description of symbols used in blood-group systems is given.


[Smallpox vaccination--Waterhouse-Friderichsen syndrome (author's transl)]. A fatal acute meningococcal sepsis (Waterhouse-Friderchsen syndrome) appearing 25 days after smallpox vaccination (re-vaccination) on military service is reported. In order to assume a causal connection between the vaccination reaction and the acute infectious complication on atypically long "unspecific negative phase" after the vaccination is postulated. The morphological findings at the vaccination pustule, which shows the same changes as a first vaccination, also support a pathological post-vaccinal course. In consideration of these observations, revaccination after 20 years is apparently a risk.


Abuse of inhalation anesthetic drugs.

Abuse of inhalation anesthetic drugs. Abuse of inhalational drugs used to produce anesthesia has progressed pari passu with their evolvement and may exist far into the future. It occurs among both professional and lay people and is fraught with toxicological and sociological hazard in excess of many other forms of substance abuse.


[Genome organization in eukaryotes].

[Genome organization in eukaryotes]. The review discussed problems of genome organization in the chromosomes of eukaryotes based on the data of genetical and molecular-biological studies. Particular attention is paid to the peculiarities of organization of genetic material in Drosophila. The main (euchromatic) part of the genome is considered as the totality of separate functional units (chromomere, gene loci), which have in the average a higher excess of DNA compared to the sized of the structural gene. The possible ways of internal organization of these units and the role of different types of DNA sequences in their function are discussed. The features of organization and function of the heterochromatic regions of chromosomes consisting of simple sequences of satellite DNA and tandemly repeated genes (polygenes), that code for general cellular functions (similar to the ribosomal genes) are considered. The instability of the number and even the sites of localization of polygenes in the chromosome, which can be determined by the peculiarities of their functions during differentiation of somatic cells is notes.


[Vision with moving eyes].

[Vision with moving eyes]. Recent microelectrode studies of single neurons of the retina, lateral geniculate nucleus, superior colliculus, and visual and parietal cortex are related to the problems of visual stability, prevention of fading, control of eye movements, and visual attention.


[3H]-Thyroliberin (TRH) binding to nuclei isolated from a pituitary clonal cell line (GH3). [3H]Thyroliberin (TRH) has been previously shown to enter its target GH3 cells. Intracellular [3H]-TRH was found chemically unmodified and associated to organites, cytosol and nucleus. We studied the [3H]-TRH binding capacity of a highly purified nuclear fraction isolated by an original procedure from GH3 cells. The nuclei still presented their double nuclear envelope. They are able to bind [H]-TRH to the same extent as nuclei isolated from GH3 cells previously exposed to [3H]-TRH. The equilibrium of binding was reached after 2--5 min incubation at 25 degrees or 35 degrees C. The binding is stable at 4 degrees C and partially (50%) dissociated within 15 min at 25 degrees C. 50% of the binding was inhibited by large excess of unlabelled TRH. Nuclei obtained from a variant GH3 cell which has lost its responsiveness to TRH presented only the noncompetitive binding compartment. The binding was found dose dependent and not saturable. Two apparent dissociation constants were evaluated: 1.5--2.5 x 10--8M and 2.10--6M, respectively, for high and low doses of [3H]-TRH. The first one was identical to that previously found for intact GH3 cells. The present data show the existence of specific nuclear binding sites for TRH, establish their characteristics and suggest a possible nuclear site of action for that peptide hormone.


[Various prognostic elements in childhood epilepsy in the light of selected materials of the Department of Developmental Neurology, Medical Academy in Gdańsk]. The purpose of the work was establishing prognostic factors in childhood epilepsy with particular reference to older children after the age of puberty. Of the total number of 138 children in 84 the seizures didn't return during follow-up from 2 to 11 years or more. Good prognosis was associated with seizures (with the exception of temporal-lobe seizures, salaam seizures and seizures limited to one half of the body) of gestation-perinatal or traumatic aetiology appearing for the first time between the age of 3 and 10 years, occurring rarely and treated early and systematically, and also cases without abnormalities in neurological examination.


Juvenile type of generalized ceroid-lipofuscinosis (Spielmeyer-Sjögren syndrome1 II. Biopsy findings. Rectal biopsies were obtained from 11 children, clinically presumed to suffer from the juvenile type of generalized ceroid-lipofuscinosis. In addition, sural nerve biopsies were performed in 4 cases. Of the various staining procedures applied for light microscopy, Sundan Black B was found to be the most useful, revealing in each of the rectal biopsies at least some nerve cells with coarse black droplets as well as numerous mucosal macrophages with a more greyish, dustlike material. In sural nerve biopsies a slight reduction of the thick myelinated nerve fibers was seen in two cases, accompanied by regeneration phenomena. The latter were also detectable in one other case, the remaining sural nerve biopsy being histologically unremarkable. By electron microscopy neuronal perikarya revealed lipopigment bodies with a fingerprint-like pattern in each of the rectal biopsies. In one case only was this pattern combined with distinct curvilinear profiles. In 4 cases, however, the fingerprint-like deposits were intermingled with different lamellated bodies, some of them reminiscent of MCB's or zebra bodies. In two of the 4 cases, these were even seen exclusively in some neurons. In each of the rectal as well as the sural nerve biopsies, most of the non-neuronal cell types presented lipopigment bodies, likewise, displaying both curvilinear and fingerpring-like profiles, with some characteristics related to the various cell types. With regard to generalized ceroid-lipofuscinosis the diagnostic value of rectal biopsies, though being disputed in the literature, appears reestablished by the findings presented.


Juvenile type of generalized ceroid-lipofuscinosis (Spielmeyer-Sjögren syndrome) I. Clinical findings. Thirteen patients with the clinical course of the juvenile type of generalized ceroid-lipofuscinosis were examined clinically, ophthalmologically, neurologically and psychiatrically. This included registration of EEG, x-ray, brain scintigraphy, motor nerve conduction velocity, ERG, fundus photography and bioptical investigations including electron microscopy. The children suffered from progressing decrease of visual acuity, decline of mental capacities, and later on speech and gait disturbances. The most characteristic findings are presented in case reports, two tables and fourteen pictures.


Effects of plant and animal lipids rich in docosenoic acids on the myocardium of Cynomolgus monkeys. Cynomolgus monkeys (Macaca fascicularis) were fed diets containing 25% rapeseed oil (RSO), partially-hydrogenated herring oil (PHHO) or a 3:1 mixture of lard/corn oil as control (CON) for 4 months. The RSO contained approximately 25% of the fatty acids as erucic acid (cis-docos-13-enoic, 22:1w9) while the PHHO contained a similar concentration of mainly cetoleic acid (cis-docos-11-enoic, 22:1w11). The CON contained no 22:1 acids. The monkeys developed the expected myocardial lipidosis, somewhat more pronounced in the RSO than the PHHO group, but small foci of mononuclear cell infiltration, while infrequent, occurred in all three groups. Significant intergroup differences in biochemical or hematologic measurements of serum constituents were an increase in serum cholesterol concentration in the RSO group and an increase in serum glutamicoxaloacetic transaminase activity in both RSO and PHHO groups at certain intervals. The shorter proportion of M. fascicularis life span represented by this experiment may account for the absence of clear intergroup differences such as are reported in rats used in similar studies.


Development of digestive enzymes in the piglet from birth to 8 weeks. II. Intestine and intestinal disaccharidases. The changes with age of intestinal mucosa, protein, lactase, maltase and sucrase were followed in the piglet between day 105 of gestation and 8 weeks after birth. Lactase and maltase activities appeared during fetal life in the whole of the small intestine. Activity of sucrase was recorded after the 1st postnatal week. Lactase activity was high at birth and reached a maximum at 1 week (X 2.5); maltase activity which was low at birth increased to the 8th week (X 143). Activities of all enzymes were low in the duodenum; lactase was most active in the jejumum. Similar activities of maltase and sucrase were found in the two distal parts of the small intestine. Specific activity (related to protein content) of lactase reached a maximum at the end of the 1st week after birth and decreased afterwards. Specific maltase and sucrase activities were higher in the 2nd week, decreased between the 2nd and 4th week and increased afterwards (maltase) or decreased to the 6th--8th week (sucrase).


Address of the President. Look around with awareness. In conspectus, consideration is given to the first "academy" in ancient Greece, current national health goals, change affecting health and medical care in the United States, and evolution--as well as the promising future--of the American Academy of Ophthalomology and Otolaryngology. Contemplating the future, the advice of James Thurber is increasingly valid: "Look backward not with anger, nor forward with fear, but look around with awareness."


Spontaneous regression of induced parotid gland tumors in rats. Pellets of powdered DMBA were implanted in the parotid glands of inbred male Fischer rats, and all experimental animals in which the carcinogen was implanted for 8, 10, 12, and 14 weeks developed well-differentiated squamous-cell carcinomas. When the carcinogen was implanted for longer periods of time, tumors developed in a smaller percentage of the experimental animals. Also, the weight of the parotid glands continued to increase with time following implantation of DMBA, reaching its highest level after 10 weeks, and then gradually decreasing with time. Different possible explanations for the regression of the induced parotid tumors are offered.


Newborn screening for maple syrup urine disease (branched-chain ketoaciduria). Routine newborn screening for maple syrup urine disease (MSUD) has been conducted since 1964, and more than 9 1/2 million newborns throughout the world have been tested with use of a bacterial inhibition assay (BIA) for leucine on dried filter paper blood specimens. Forty-three confirmed cases of the "classical" and the "intermediate" variant forms have been detected. The frequency of MSUD, based on these data, is approximately one in 224,000 newborns. The sensitivity and the specificity of the leucine BIA are demonstrated. There are several problems in routine screening for MSUD, including the fact that the "intermittent" variant form will be missed. A brief summary of the clinical course of the 13 cases detected by our collaborative laboratories is presented.


Residues of organochlorine pesticides and polychlorinated biphenyls and autopsy data for bald eagles, 1973-74. Eighty-six bald eagles found sick or dead during 1973-74 in 24 States were analyzed for organochlorine compounds. DDE was detected in all caracasses; polychlorinated biphenyls (PCB's) were found in all but two. Seventy-five carcasses contained TDE and/or dieldrin. Four eagles had possibly lethal levels of dieldrin in the brain. Bald eagles continue to retain high residue levels of organochlorine pollutants. Illegal shooting remained the most common cause of death but accounted for a smaller percentage of the mortalities than in the two previous biennial collections.


[Anaerobic infections of domestic animals excluding enterotoxaemias (author's transl)]. With the advent of improved techniques for anaerobic cultivation on recent years increased interest in anaerobic infections has occurred. Against this background the present study presents a survey of those animal diseases (with the exception of the enterotoxaemias) in the pathogenesis of which anaerobic bacteria are involved.


Masking, De Lange curves and integration time as revealed by the electroretinogram of a tree shrew (Tupaia chinensis). Dynamical characteristics of the electroretinogram (ERG) of a tree shrew were measured. Since this animal has a cone dominated receptor population (95%) comparison to human photopic vision is obvious. The light source was chosen to stimulate the red cones of this deuteranopic animal predominantly. Masking experiments displayed a reasonable correspondence to human foveal psychophysics. De Lange curves and CFF values revealed a maximum sensitivity at 15-20 HZ, which is higher than is found for human vision. A secondary maximum was observed in the De Lange curves at high adaptation levels, which is possibly due to interactions of the ERG components. The dependency of integration time on adaptation level appeared to be similar to known data of human psychophysics and electrophysiological data from Limulus receptor cells.


[The sella turcica and pituitary function in congenital hypothyroidism due to thyroid ectopia or hypogenesis (author's transl)]. Nine patients suffering from hypothyroidism due to thyroid ectopia or hypogenesis, with a large sella turcica, were examined at adolescence or during adult life. TSH, prolactin and growth hormone function were studied. Basal plasma TSH, evaluated in 5 cases, was raised and responded explosively to stimulation with TRH. The administration of L-dopa was not associated with any notable changes in TSH. In one case, the chronic administration of l-T3 resulted in a fall followed by normalisation in plasma TSH levels. Basal plasma prolactin, explored in 6 patients, was high in 4 females and normal in 2 males. TRH stimulation resulted in a marked increased in prolactin in the female cases and a moderate increase in the male cases. L-dopa caused a fall only in high prolactin values. Stimulation of GH by argininehydrochloride, insulin hypoglycaemia and L-dopa gave variable responses. In one case, substitutive thyroid hormone therapy restored the GH response to L-dopa and arginine hydrochloride to normal. Paradoxically, GH increase following stimulation with TRH.


[Total parenteral nutrition in the adult. Theoretical aspects (author's transl)]. When oral or enteral feeding becomes impossible or inadequate, total parenteral nutrition makes it possible to reduce the occurrence of malnutrition states as complications of medicosurgical disorders. From a practical point of view it should provide a minimum fluid intake of 30 ml/kg with a nitrogen intake of the order of 150 to 300 mg/kg/day with sufficient quantities of all essential amino acids in a balanced ration. In most instances the calorie intake should be 40 to 60 Kcal/kg/day. Non-protein calories are obtained from carbohydrates or fats but the ideal percentage of each of these two nutrients is not known. In order to be effective and well tolerated, intravenous nutrition of this sort must be adapted to each patient and should be administered by a qualified medical and nursing team in order to minimise the metabolic and septic risks secondary to the techniques used.


Folded chromosomes of vegetative Bacillus subtilis: composition and properties. The isolation of folded DNA from Bacillus subtilis, a Gram positive bacterium is described. When the lysis was achieved with 1 M NaCl a slow sedimenting nucleoid was obtained (1600-2000 S). Conversely, when the lysis was achieved with 0.2 M NaCl a fast sedimenting nucleoid was obtained (3500-4000 S). The yield of folded DNA was between 80 to 90 % of the total lysate DNA. Both nucleoids contained the same amount of RNA, but the relative proportions of lipids and proteins were different. Folded chromosomes were prepared in the presence of spermidine: artifactual protein binding is shown to be unlikely. Electrophoresis of nucleoid proteins showed a dominant polypeptide (MW = 36,000), which remained associated with DNA after sarcosyl treatment and could be partially removed by heat mediated DNA unfolding. In vitro transcription by endogenous RNA polymerase bound to the fast sedimenting-nucleoid was rifamycin resistant; the template capacity of the fast sedimenting-nucleoid was compared with that of the completely unfolded chromosomes.


Nucleotide sequence of threonine tRNA from Bacillus subtilis. A threonine tRNA was purified from Bacillus subtilis W168 by a combined use of column chromatographic systems. The nucleotide sequence was determined to be pG-C-C-G-G-U-G-U-A-G-C-U-C-A-A-U-D-G-G-D(U)-A-G-A-G-C-A-A-C-U-G-A-C-U-mo5U-G-U-t6A-A-psi-C-A-G-U-A-G-m7G-U-U-G-G-G-G-G-T-psi-C-A-A-G-U-C-C-U-C-U-U-G-C-C-G-G-C-A-C-C-AOH, where about 40 % of D20 remained unmodified as U20. It consists of 76 nucleotides including a new minor nucleoside, 5-methoxyuridine (mo5U), which occupies the wobble position of anticodon.


Enzymatic synthesis of a segment of bacteriophage Qbeta coat protein gene. The oligoribonucleotide, A-A-A-C-U-U-U-Gp, constituting a segment of RNA bacteriophage Qbeta coat protein gene was efficiently synthesized at a milligram scale by a combination of enzymatic methods using bacteriophage T4 RNA ligase and the thermophilic polynucleotide phosphorylase. A-A-A-Cp was synthesized from A-A-A and pCp by the newly developed mononucleotide addition method using T4 RNA ligase in a yield of 83%, followed by dephosphorylation with bacterial alkaline phosphatase to obtain A-A-A-C. pU-U-U-Gp was synthesized from pU-U-U and GDP by the simultaneous action of polynucleotide phosphorylase and RNase T1 in a yield of 32%. finally, the two oligonucleotides (A-A-A-C and pU-U-U-Gp) were ligated with T4 RNA ligase and the octanucleotide, A-A-A-C-U-U-U-Gp, was obtained in a yield of 85%.


Effect of insulin in the induction and regression of experimental cholesterol atherosclerosis in the rabbit. A study was undertaken to determine the effects of long-term insulin therapy on the development and regression of lipid perturbations and experimental cholesterol atherosclerosis in rabbits: (1) Insulin administration for 15 days significantly reduced plasma lipid levels and free fatty acids in rabbits fed a high-cholesterol diet; it also inhibited the effects of a single dose of cholesterol. Paradoxically, continued insulin treatment led to the reinforcement of lipaemia through the stimulation of mobilization. Insulin administration during the development of atherosclerosis significantly aggravated the fatty infiltration of the aortic tissue and the lesions of the vessels, and also increased the frequency of coronary lesions. (2) In rabbits fed a cholesterol enriched diet during two months and then a normal diet, insulin treatment accelerated the rate of reduction of hypercholesterolaemia, but aggravated the lipid infiltration of the artery walls, and also prevented regression of coronary atherosclerosis.


Dense plexus of substance P immunoreactive nerve terminals in eminentia medialis of the primate hypothalamus. The indirect immunofluorescence technique of Coons and collaborators was used to study the distribution of substance P-like and luliberin (luteinizing hormone-releasing hormone)-like immunoreactivity in the eminentia mediana (eminentia medialis or infundibulum) of rats, monkeys, and human beings. In rats, abundant luliberin-positive fibers were present in the external layer (mainly lateral parts) whereas almost no substance P-immunoreactive nerves were observed in this region. In contrast, in the external layer of the primate eminentia medialis a dense plexus of substance P-positive nerve terminals was observed close to the blood vessels supplying the anterior pituitary gland. Luliberin-immunoreactive fibers were also present, but with a more even distribution all over the eminentia medialis and in lower numbers. The present findings indicate that substance P may play a role in the control of hormone secretion from the anterior pituitary, either by being released into the portal vessels, i.e., acting as a releasing or inhibitory hormone, or by an action as local regulator (modulator or transmitter) at the level of the eminentia medialis. Thus, in agreement with many earlier studies, substances other than the "classical" releasing and inhibitory hormones may be important for the regulation of the pituitary gland. Furthermore, there may exist marked species differences with regard to the type of substances involved in the central control of the pituitary.


[Lysis of the cell walls of streptococcus group A by Streptomyces griseus pronase]. The effect of Streptomyces griseus pronase on Streptococcus group A cell walls was studied. Cell walls were shown to be lysed by pronase, the lysis level being dependent on the molarity of the potassium-phosphate buffer used. With an increase in the buffer molarity from 0.005 M to 0.05 M lysis of cell walls decreased from 70-80% to 30%. By DEAE-cellulose chromatography lysates were separated into two fractions the first of which contained a group specific polysaccharide. A preparative method of obtaining a group specific polysaccharide of Streptococcus group A using Streptomyces griseus pronase under mild conditions is described.


Nonequivalence of alpha-bungarotoxin receptors and acetylcholine receptors in chick sympathetic neurons. alpha-Bungarotoxin binds selectively to chick sympathetic neurons that are responsive iontophoretically applied acetylcholine. alpha-Bungarotoxin (125 nM) does not affect the response of cultured neurons to acetylcholine, nor does it affect a cholinergic synaptic potential recorded from sympathetic ganglia. d-Tubocurarine (100 muM) inhibits alpha-bungarotoxin binding and blocks acetylcholine receptor function in both preparations, but alpha-bungarotoxin does not protect acetylcholine receptors against d-tubocurarine blockade of acetylcholine responses. The receptor for alpha-bungarotoxin can be extracted from neuronal membranes with nonionic detergents and, when assayed by velocity sedimentation in sucrose gradients, sediments at a rate faster than that of skeletal muscle acetylcholine receptors. Treatment of alpha-bungarotoxin-receptor complexes with glutaraldehyde (0.1%, wt/vol) increases their stability from a half-time for dissociation of 3.5 hr to greater than 6 days at 23 degrees. This permits a quantitative assay of alpha-bungarotoxin-receptor complexes after relatively long periods of velocity sedimentation. It is concluded that alpha-bungarotoxin does not bind to the acetylcholine-binding site of neuronal acetylcholine receptors. These results compel a reevaluation of studies that assume that alpha-bungarotoxin is a specific ligand for neuronal acetylcholine receptors.


[Role of the adrenal glands and the testes in the formation of the sex steroid pool in the peripheral blood of male monkeys]. A study was made of formation of the pool of sex steroid hormones and their precursors in the blood plasma of male Paio hamadryas. Cannulation and simultaneous recovery of the blood from the adrenal, testicular, left iliac veins and the aorta were carried out under nembutal anesthesia. Thirteen steroid hormones and their precursors were determined by the radioimmunological method in all the blood portions. Steroid function was tested on columns with celite. Pregnenolone, 17alpha-oxypregnenolone, and 17alpha-oxyprogesterone were secreted chiefly by the adrenal glands. Dihydroepiandrosterone was produced by the adrenal glands and utilized by the testes. Androstendion and dihydrotestosterone were mostly of adrenal, and testosterone--testicular origin. Estron is secreted by the adrenal glands only, whereas estradiol is produced by the testes in larger quantities than by the adrenal glands. The sulfate forms of pregnenolone and dihydroepiandrosterone are produced chiefly by the adrenal glands.