A Waldenström macroglobulin that is both a cold agglutinin and a cryoglobulin because it binds N-acetylneuraminosyl residues. A purified human monoclonal IgM(kappa) (cold agglutinin MKV) has been characterized as both a cold agglutinin and a cryoglobulin. Since its reactivity with human erythrocytes but not with dog erythrocytes is reduced by treatment of the cells with ficin and its reactivity with both is abolished by treatment of the cells with neuraminidase, it has by definition Pr(2) specificity [Roelcke, D. (1974) Clin. Immunol. Immunopath. 2, 266-280]. Presumably, the membrane receptors for cold agglutinin MKV are sialic acid-containing glycoproteins in human cells and sialic acid-containing glycolipids in dog cells. Agglutination of erythrocytes is specifically inhibited by II(3)-N-acetylneuraminosyllactosylceramide (GM(3)) and N-acetylneuraminosylparagloboside but not by their N-glycolylneuraminosyl forms or by lactosylceramide or paragloboside, and the reactivity of neuraminidase-treated cells can be restored by allowing them to absorb either GM(3) or N-acetylneuraminosylparagloboside. When large amounts of ganglioside are absorbed, the cells are agglutinated not only in the cold, but also at 37 degrees , showing that the density of receptor sites on the erythrocyte surface can influence the thermal amplitude of cold agglutinins. Liberation of sialic acid from cold agglutinin MKV by treatment with neuraminidase (acylneuraminosyl hydrolase; EC 3.2.1.18) does not affect its agglutinating properties but the asialoprotein is no longer a cryoglobulin. Apparently the physical basis for its precipitation in the cold is the intermolecular immune binding of N-acetylneuraminosyl residues.


Segregation at a locus determining an immunoglobulin genetic marker for the light chain variable region affects inheritance of expression of an idiotype. Previous investigations have demonstrated close genetic linkage between loci governing expression of strain-specific idiotypes and immunoglobulin heavy (H) chain allotype (i.e., the C(H) locus). This linkage is presumed to reflect polymorphism of V(H) genes (or of their expression) linked to the polymorphic C(H) locus. That there was no apparent involvement of light (L) chain loci (thought to be unlinked to H chain) in inheritance of the idiotype-positive (Id(+)) phenotype was surprising, because the L chain is required for formation of each of the idiotypes studied at the chemical level. However, previous studies involving backcrosses of F(1)(Id(+) x Id(-)) mice to the Id(-) parental strain have never employed as the Id(-) parent one of several inbred strains shown by G. M. Edelman and P. D. Gottlieb [(1970) Proc. Natl. Acad. Sci. USA 67, 1191-1199] to express a V(L)-region polymorphism. Among backcrosses performed in the present study, one involved the A/J strain as the Id(+) parent and the PL/J strain, one of the several strains with and L chain polymorphism, as the Id(-) parent. Whereas in three other backcrosses performed, idiotype expression segregated with H chain allotype, in the backcross to PL/J, all mice producing the characteristic A/J Id(+) phenotype were A/J allotype(+), but not all A/J allotype(+) mice were Id(+). Typing of backcross progeny for the Ly-3 thymocyte alloantigens, controlled by a locus closely linked to that governing the L chain polymorphism (called the VK-1 locus), indicated that only the Ly-3 heterozygotes expressed the characteristic A/J Id(+) phenotype. Thus, all Id(+) backcross mice inherited both the H chain allotype and the Ly-3 locus (and closely linked L chain-related locus) from the Id(+) A/J strain. This suggests that, when strains with L chain polymorphisms are included in genetic studies of idiotype expression, segregation of loci governing L chain expression may be found to contribute to inheritance of the Id(+) character. In addition, these studies may be taken as further evidence that the V(L)-region repertoire of the PL/J strain may differ considerably from that of most other inbred strains of mice.


Sedimentation properties of the scrapie agent. The sedimentation behavior of the scrapie agent in homogenates of spleen from infected mice has been determined. Approximately 90% of the scrapie agent was sedimented at an omega2t value of 3 X 10(10) rad2/sec in a fixed-angle rotor. Sedimentation of the agent was not substantially affected by sonication or by treatment with the detergent sodium deoxycholate. The sedimentation profiles of the scrapie agent were similar to those observed for free polyribosomes, but differed from those exhibited by five other subcellular markers. Comparative studies showed that the sedimentation profiles of subcellular markers in spleen suspensions from mice infected with scrapie did not differ from uninoculated controls. These studies suggest that the scrapie agent is a discrete infectious particle which should be separable from cellular membranes.


Sensory electrophysiology of bacteria: relationship of the membrane potential to motility and chemotaxis in Bacillus subtilis. The relationship of membrane potential to motility and chemotaxis of Bacillus subtilis has been tested by using the fluorescence of a cyanine dye as a probe of the potential. The dye fluorescence was found to be an indicator of membrane potential by correlation with triphenylmethylphosphonium ion distribution and with changes due to anaerobicity and ionophore addition. When the potential was sufficient for motility and constant over time, it was found that the absolute level of the potential did not affect the swimming behavior of the bacteria. Transient alteration of the membrane potential did, however, lead to changes in swimming behavior. Attractants were found to alter the swimming behavior of the bacteria without altering the membrane potential. Thus, change of the overall membrane potential of a normal B. subtilis is not required for chemotaxis, but such a change is sensed by the bacteria just as changing levels of attractants and repellents are sensed.


Cloned segment of Drosophila melanogaster rDNA containing new types of sequence insertion. A cloned 14.3-kbase segment of Drosophila melanogaster rDNA (Dm207) is described in which only a 4-kbase region is homologous to a cloned 17-kbase rDNA repeating unit, Dm103; this 4-kbase region consists of part of the 28S rRNA gene and most but not all of the adjacent transcribed spacer that normally connects the 18S and 28S genes. The transcribed spacer in Dm207 is interrupted by a 2.2-kbase stretch of DNA that does not contain any 18S gene sequences. At the other end of the 4-kbase homology, the 28S gene is interrupted by an 8.1-kbase stretch of DNA at a position equivalent to the site of the 28S insertion found in the 17-kbase units. The question of whether the 2.2-kbase and 8.1-kbase interrupter segments in Dm207 derive from longer insertions into the transcribed spacer and 28S genes of a very long repeating unit (greater than or equal to 22 kbases) or represent a region of the chromosomal DNA into which a 4-kbase fragment of rDNA has been inserted is discussed.


Translation of Drosophila melanogaster sequences in Escherichia coli. Thirty-seven independently cloned segments of Drosophila melanogaster DNA (Dm segments) were individually tested for their ability to promote the synthesis of new polypeptides in Escherichia coli K-12. The cloning vector was the pSC101 plasmid and the test system consisted of E. coli K-12 minicells that contained the hybrid pDm plasmids. Each of four pDm plasmids produced a new polypeptide, and one, pDm107, was selected for detailed mapping of the sequences required for the translation of its 38,000-dalton polypeptide, the Dm107 protein. Mapping was accomplished by constructing (i) deletion derivatives of pDm107 and (ii) new plasmids consisting of fragments of the Dm107 segment inserted into other vectors, and then testing these hybrids for their ability to promote the synthesis of the Dm107 protein, or truncated versions of this protein, in minicells. The 1000 base pairs of sequences that are translated to yield the Dm107 protein were thereby mapped at the center of the 18,000-base pair Dm107 segment, which consists of nonrepetitive sequences located at the base of the right arm of chromosome 2. The four polypeptides produced by the four pDm plasmids require sequences of 4000 base pairs for their translation, and the total amount of DNA in the 37 cloned Dm segments that were tested is approximately 400,000 base pairs. Because no new polypeptides were detected with the remaining 33 pDm plasmids, the fraction of D. melanogaster sequences that can be efficiently translated in E. coli K-12 is estimated to be 1 x 10(-2).


Proteolysis associated with normal, carcinogen-treated, and transformed rat liver epithelial cells. A method was developed to distinguish between cell surface-associated and released proteolytic activity. The approach utilizes 125I-labeled protein substrate covalently linked to modified latex beads. These beads are either rolled over the surface of cells grown in culture or next to the cells. Using this method we have studied normal, carcinogen-treated and spontaneously transformed rat liver epithelial cells. Transformed cells always released greater amounts of radioactivity than carcinogen-treated or normal hepatocytes when the beads were presented next to the cells, indicating an enhanced release of proteolytic enzymes. When the substrate was in contact with the viable cell surfaces both the carcinogen-treated and transformed cells released more radioactivity from the beads' surface than the tissue culture-adapted normal cells. This enhanced proteolytic cleavage indicated that there is an altered surface topology or an increased surface-associated enzyme activity on both the carcinogen-treated and transformed cells.


Esophageal cannulation for oral drug administration in the sub-human primate. A technique of esophageal cannulation used in rats was adapted for use in the sub-human primate. Cannulation of the esophagus requires general surgical skills and a very short postoperative recovery period. No interference in eating habits or tendency toward vomiting was noted following cannulation. This technique allows the investigator an effective method for oral dosing of drugs with minimal physical and emotional stress to the animals and is quite appropriate for oral drug self-administration studies.


Effects of methadone and morphine maintenance on drug-seeking behavior in the dog. The effects of methadone and morphine maintenance on morphine self-administration were studied in the dog. Methadone was given passively for 2 weeks by continuous i.v. infusion. The amount of methadone administered daily was the same in mg/kg as the mean daily mg/kg of morphine the dogs had self-administered during the premaintenance control week. Morphine self-administration was markedly reduced initially but returned to normal levels within 2 weeks of methadone administration. Following the methadone maintenance period, morphine self-administration was increased over the premaintenance period for 2 weeks. A result similar to that with methadone was obtained in a second experiment when morphine was used as the maintenance drug in an amount that was three times the amount the dogs had been self-administering during the premaintenance control week.


Repression of a lithium pump as a consequence of lithium ingestion by manic-depressive subjects. The lithium pump in human erythrocyte membranes, which is responsible for extrusion of lithium against a concentration gradient, has been found to be reversibly repressed during periods of lithium carbonate administration. The pump activity of patients prior to lithium therapy is not different from controls. The onset of repression may require several days to several weeks and occurs at specific individual threshold levels of lithium carbonate dosage. Reactivation of the lithium pump occurs sometime after the dosage is discontinued. We postulate that repression of the lithium pump results from systemically available factors which alter membrane structure, and suggest that is such changes also occur in the central nervous system, they may provide insight into one means by which lithium produces its psychotropic affects.


Effects of d-amphetamine on responding simultaneously maintained and punished by presentation of electric shock. Responding of two squirrel monkeys with a previous avoidance history was developed and maintained under a multiple fixed-interval 10-min schedule of food and electric shock presentation. Under this schedule the first response after 10 min produced either food or shock depending on the prevailing stimulus condition. Subsequently, responding maintained by food was suppressed when each 30th response produced shock (punishment). Presentation of the same intensity electric shock (10 mA) under the fixed-interval schedule in the other component continued to maintain high positively-accelerated rates of responding. Although increases in punished responding do not usually occur with d-amphetamine, under these conditions, where responding was both maintained and suppressed by the same consequent event, d-amphetamine markedly increased punished responding. Responding maintained by the presentation of shock was also increased by d-amphetamine. The effects of d-amphetamine on punished responding can depend on specific features of the situation in which behavior is studied.


The demethylation of imipramine and clomipramine as apparent from their plasma kinetics. The demetylation of imipramine and clomipramine was studied after administration by different routes of single doses of clomipramine hydrochloride and multiple doses of clomipramine as well as imipramine hydrochloride. Five healthy volunteers received 1 mg of clomipramine hydrochloride/kg body weight as single oral and intramuscular doses on different occasions for the purpose of studying the plasma levels of clomipramine and the desmethylclomipramine formed. Desmethylclomipramine was found in the plasma in four of the subjects after oral intake but only in one subject after intramuscular injection. The peak levels of clomipramine were considerably higher after intramuscular than after oral administration. The half-lives of clomipramine after oral administration ranged from 11.6-35.8 h (M = 20.8 +/- 4.0) and after intramuscular administration from 20.1--39.6 h (M = 24.7 +/- 3.7). Twenty subjects received either imipramine or clomipramine both orally and intramuscularly during a period of 3 weeks in a crossover design. The plasma levels of imipramine and clomipramine and their demethylated metabolites desipramine and desmethylclomipramine were determined during the treatment. The ratio between the plasma level of the parent drug and its demethylated metabolite was on average twice as high during intramuscular as during oral treatment.


The effects of four antihypertensive agents on the Stroop colour-word test in normal male volunteer subjects. Sixty healthy male volunteers were randomly assigned to one of six treatment groups on a double-blind basis: 1. Atenolol = 50 mg t.d.s. 2. Methyl dopa = 250 mg t.d.s. 3. Propanolol = 40 mg t.d.s. 4. Reserpine = 0.2 mg t.d.s. 5. Placebo. 6. Control = no tablets. Tests were carried out before treatment, 2 h after the first dose, after seven doses, and after 21 doses. Subjects performance on the Stroop Colour-Word Test was assessed in terms of (a) word reading speed and (b) an 'interference' score based on the difference between the incongruous colour word and colour card reading speed. No evidience was found of central effects of the beta-blockers, but personality X drug interactions were found, particularly in the reserpine group.


Deficits in passive-avoidance learning following atropine in the developing rat. The maturation of cholinergic inhibitory mechanisms that may be involved in passive-avoidance learning was studied in rats 14, 17, 21, 25, 28, and 34 days of age. Acquisition and extinction of the conditioned response were examined under saline and atropine sulfate (5 mg/kg). Learning was also tested following scopolamine hydrobromide injections (1, 4, 8 mg/kg) in rats 17 days of age and following alpha-methylatropine (5 mg/kg) in 17- and 34-day-old groups. In normal animals the rate of acquisition increased during ontogenesis, with a significant improvement between postnatal days 17 and 21, whereas the rate of extinction did not vary with age. Acquisition was impaired by atropine sulfate at all ages and even totally prevented in younger groups (14 and 17 days of age). It was also completely disrupted by scopolamine in 17-day-old rats. Extinction following acquisition under atropine was more rapid than after normal acquisition. Methyl-atropine was without effect. These results support the hypothesis of central cholinergic mechanisms involved in response suppression, already functioning in the rat 14 days of age and maturing mainly between the 17th and the 21st postnatal days.


Effects of cyclic analogs of GABA on protein synthesis and discrimination learning. Three cyclic analogs of gamma-aminobutyric acid (GABA)-5-ethyl, 5-phenyl, 2-pyrrolidinone (EPP), 5-diphenyl, 2-pyrrolidinone (DPP), and 5-methyl, 5-phenyl, 2-pyrrolidinone (MPP)- were studied in relation to protein synthesis and the latter in relation to discrimination learning. The present study shows that when different groups of rats were injected subcutaneously with 10 mg/kg of EPP or DPP, the protein synthesis in vitro was inhibited 75% in brain mitochondria. MPP at the same doses was the less potent inhibitor of mitochondria protein synthesis. Experiments on discrimination learning show that 10mg/kg of MPP enhance the response decision speed in presence of S(+) (white arm) and S(-) (black arm).


Naloxone-precipitated withdrawal as a function of the morphine-naloxone interval. Withdrawal was precipitated by naloxone at different intervals, up to 22.5 h, following a last maintenance injection in morphine-dependent rats. Different symptoms of withdrawal were found to be preeminent following different morphine-naloxone intervals. Locomotor activity, jumping, and writhing were precipitated most frequently at shorter intervals after the last morphine injection; teeth chattering, wet dog shakes, ptosis, diarrhea, penile ejaculation, and hypothermia, at longer intervals. Others, including hostility, rhinnorhea and lacrimation did not change in frequency over the intervals measured. This order closely resembled that in which symptoms occurred as a result of withdrawal abstinence alone, though they were somewhat advanced in time. The results were discussed in relation to previously reported observations of naloxone-precipitated withdrawal, and in terms of their implications for a general theory of morphine withdrawal.


Sedative properties of doxepin in comparison with diazepam. Doxepin (Quitaxon) at doses of 25, 50, and 75 mg was compared with diazepam 7.5, 15, and 22.5 mg, using as variables the percentage lowering of Critical Flicker Fusion (CFF) and the self-estimated degree of drowsiness. Single doses were given, and repeated effect determinations were made over 6 h. Clear dose-effect relations could be demonstrated. The two drugs differed in speed and duration of action and in steepness of effect increase with dose. Although there were good correlations between CFF effect and subjective drowsiness, it seemed that the two methods interrelated somewhat differently in the different types of drug. CFF was a more stable and reliable method than the subjective estimation of drowsiness. However, when comparing drugs belonging to different classes, both methods preferably should be used together.


Interaction between delta(9)-tetrahydrocannabinol and d-amphetamine. d-Amphetamine increases the motor activity at a dose range of 0.5-4 mg/kg. delta(9)-Tetrahydrocannabinol (THC) diminishes this effect dose-dependently. Also, the hyperthermia caused by 5 mg/kg d-amphetamine is antagonized by THC, whereas the d-amphetamine induced stereotype movements (above 4 mg/kg) are prolonged by the cannabinoid. THC and d-amphetamine both reduce the food and water intake and the normal development body weight of rats. In combination the two substances have an additive effect. Rats treated with 5 mg/kg d-amphetamine show a significant enhancement of the dopamine (DA) concentration (26%) in the brain stem 2 h p.i. Pretreatment with 10 mg/kg THC, which also causes an increase of DA by 15%, raises the DA content by 50%. Norepinephrine (NE) in the brain stem and hypothalamus is reduced by d-amphetamine but THC has no effect on the concentration of this monoamine. After subchronical treatment with THC tolerance is demonstrable to all THC effects tested. But there is no cross tolerance between delta(9)-THC and d-amphetamine since the pharmacological as well as the biochemical effects of d-amphetamine occur despite the subchronical treatment with THC.


Perlapine: relationship between stimulation of prolactin secretion and antipsychotic activity. Perlapine is a dibenzohetereopine compound chemically related to clothiapine, loxapine, and clozapine. Although the latter three compounds are antipsychotic, perlapine has not been reported to be antipsychotic. Nevertheless, all four drugs increase rat plasma prolactin levels. The order of potency is loxapine, perlapine, clothiapine, and clozapine. These results suggest that either perlapine should be reexamined for antipsychotic properties or there are hitherto unsuspected discrepancies between the dopamine receptors relevant to antipsychotic activity in man and those that regulate prolactin secretion in the rat.


The antagonizing effect of aspartic acid on the brain levels of monoamines and free amino acids during the development of tolerance to the physical dependence on morphine. Since it has been shown in previous study that aspartic acid prevents the development of physical dependence on and tolerance to morphine and antagonizes the abstinence syndrom signs, the biochemical bases of that prevention were investigated in the present study. The brain contents of serotonin, DA, NA, and free amino acids of the rats given aspartic acid and morphine separately and in combination were determined. It has been observed that most of the morphine-induced changes in the brain were normalized in the group given aspartic acid and morphine together. The relative ineffectiveness of aspartic acid in normalizing some amino acid levels decreased by morphine was discussed and some logical explanations were found.


The development of tolerance to morphine in the rat. Tolerance to various effects of morphine in the rat can be quantified by means of a shift of semi-logarithmic dose-response curves. Tolerance to analgesia (hot plate, acetic acid writhing), catalepsy, and the tilted plane develops in a closely similar manner. Also, the stimulating effects of about 1 mg/kg morphine-HC1 tested in an open-field procedure are somewhat less pronounced in chronically treated rats than in naive ones. There is no correlation between tolerance development and the acute ED50 of different tests.


Long-term behavioural and biochemical effects following prolonged treatment with a neuroleptic drug (flupenthixol) in rats. The effects of long-term treatment (36 weeks) with a neuroleptic drug (flupenthixol) were investigated behaviourally and biochemically in rats. Sixteen rats were trained on a DRL (differential reinforcement of low rate) 15-s schedule until stable responding was obtained. During the following 36 weeks 9 rats were injected weekly with flupenthixol dissolved in Viscoleo [4 mg/kg(i.m.)] and seven rats received Viscoleo alone. During this period the animals were not run on the DRL schedule. Retesting on DRL 7 weeks after the last drug injection yielded highly significant differences between the flupenthixol-treated animals and the controls. Thorough neurological examinations of the animals just preceeding the retesting period also revealed some deficits in the flupenthixol-treated animals. At sacrifice, 14-18 weeks after the last drug injection, levels of homovanillic acid (HVA) were measured in the corpus striatum and total 3-methoxy-4-hydroxyphenylglycol (MOPEG) in the rest of the forebrain. The results indicate a nonsignificant increase of 25% in the dopamine metabolite HVA, while the noradrenergic metabolite MOPEG was significantly decreased by 14% in experimental animals. The possibility of persistent functional and biochemical effects produced by prolonged treatment with a neuroleptic drug is highlighted in the results presented here.


Kinetics of distribution of amphetamine in cats. The distribution and metabolic fate of amphetamine were studied in cats. In the brain, high levels of drug were detected in the grey matter structures at short intervals after administration, while at longer intervals distribution between white and grey matter areas was more uniform. In peripheral tissues the greatest concentration of the drug was seen in the highly vascularized organs. Para-hydroxy-amphetamine was found in minimal amounts in the liver and kidneys and only at trace quantities in the brain.


Tolerance to morphine-produced discriminative stimuli and analgesia. Male hooded rats were trained in Skinner boxes to press one lever after a morphine injection (10 mg/kg) and another lever after a saline injection (1 ml/kg) on an FR 10 schedule of food reinforcement. After the drug discrimination was well established, the rats were tested for stimulus generalization at different doses of morphine, followed by assessment of tail withdrawal latency as a measure of analgesia. Subjects were then administered increasing doses of morphine sulphate to induce an increased level of tolerance. New dose-response curves indicated that tolerance developed to the morphine-induced discriminative stimulus, and to the analgesic action of morphine, but doses of morphine that failed to cause detectable analgesia still produced a pronounced discriminative stimulus.


Is early and periodic screening, diagnosis, and treatment (EPSDT) worthwhile? The State and Federal governments invest many tax dollars to provide health screening for millions of Medicaid families. Justification for such investment is based on the experience of Sweden's screening of 4-year-old children, a University of Texas Health Service Center study on cost benefit of EPSDT, and the Michigan experience. In Sweden's health screening program, health problems of functional importance were found in 21.6% of the screenees, and 71.8% of these were newly discovered by the screening. The results of Texas study indicated that an effective EPSDT program would result in a savings of $43 billion in 1976 currency over a 20-year period. In Michigan, a drop of 13% occurred in the referral rate for health problems during a 6-month period among those who were screened a second time or more.


Automatic processing quality assurance program: impact on a radiology department. A method for evaluating processing variability as well as quantitative data on a quality assurance program tested at a radiology department are presented. Thirty per cent of all retakes due to improper overall density could be attributed to processing variation; these could be prevented through a QA program which is highly cost-effective in both monetary and patient-care terms.


Arachnoiditis following myelography with water-soluble agents. The role of contrast medium osmolality. The role of contrast medium osmolality in postmyelographic arachnoiditis was studied. Monkeys were injected intrathecally with isotonic saline (290 mOs/kg), hypertonic saline (1,449 mOs/kg), metrizamide (456 or 300 mOs/kg), or methylglucamine iocarnate (1,049 mOs/kg). After 12 weeks the animals were examined for evidence of arachnoiditis, with myelography just prior to sacrifice and microscopic examination of the excised dural sac and its contents. Intrathecal injections of methyglucamine iocarmate or metrizamide caused arachnoiditis while saline did not. Only one animal given 170 mg l/ml (300 mOs/kg) exhibited a more severe reaction than the controls. An increase in the cerebrospinal fluid osmolality alone does not cause arachnoiditis.


The 3 and 2 technique for Hodgkin's disease at Memorial Hospital. This paper presents a technique for total nodal irradiation used at Memorial Hospital for the treatment of Stage IIIA and previously untreated Stage IIIB Hodgkin's disease. This method of treating large fields for this type of lymphoma overcomes problems of dosimetry and treatment tolerance. There are two courses of treatment used in which all lymph node bearing areas from the tips of the mastoids to the femoral triangles are irradiated. A comparison will be made between this technique and the conventional treatment fields for Hodgkin's disease.


Enhancement activity of anti-brucella sera in experimental Brucella abortus infection in mice. The passive transfer of rabbit anti-brucella sera promotes the multiplication of Brucella abortus in the spleen of mice infected intravenously with a low dose of this bacteria. The enhancement activity of the anti-brucella sera is related to their modes of preparation in rabbits. The agglutinin titers of all these antisera were relatively high, while there was some discrepancies in their content in haemagglutinating, immune adherence and complement fixing antibodies.


Membrane actions of daunorubicin in mammalian erythrocytes. Fresh erythrocytes from unanesthetized beagles, rhesus monkeys, rabbits and mice have increased susceptibility to hypotonic lysis after incubation for 30 minutes with high concentrations of daunorubicin. The effect is biphasic in that lower concentrations of drug decrease lytic susceptibility. EDTA diminishes the susceptibility of cells to lysis after treatment with the drug. Red cells from humans and from Sprague-Dawley rats may show either increased or decreased susceptibility to hypotonic lysis; these diverse reactions are proportional to relative fragility and reflect individual variation in the case of human cells and possibly other factors in animal cells. The species-specific and individualistic hemolytic responses suggest possible membrane sites of action for this class of drugs.


[Comparative development of the mammalian nervous system (author's transl)]. By collecting the results of research from different laboratories it has been possible to picture the probable sequence in which the nervous system develops in certain mammalian species. As the present report is to be referred to current conceptions of the development of the nervous system, special attention will be pain to comparative aspects of the question. Mammalian forms vary greatly in degree of maturity at birth, ranging from the fetus-like newborn rat to the highly mobile, almost self-sufficient, guinea-pig. As identical sequences of development will be demonstrated in both categories of mammals attention will be devoted to discussing the criteria which condition our trusting this sequence of development. Lastly, Man will be considered. It is not easy to decide whether man is a true altricial species or in what sense he can be considered as a special case of precocial species. This point is discussed: Man is altricial from the motor point of view. He is precocial from the sensory point of view and sleep develops during embryonic life in this species.


[Clinical and electrophysiological evolution of infants presenting with partial seizures before the age of two months (author's transl)]. The study was carried out on 28 children: 18 with partial seizures in the first five days of life, and among them 4 with status epilepticus; 7 had focal seizures between the first and eight week, 3 generalised tonic seizures with assymetrical EEGs. A clinical and electro-physiological study was carried out at the time of onset, 1 month later and again at 4 months. The results of the clinical and EEG examinations showed: -firstly during the seizures, the gravity of neonatal status epilepticus and of certain EEG patterns, the lack of localising value of seizures and of electroencephalographic critical discharges whereas permanent assymetry of background activity can precede by several months the appearance of clinical signs. -at the examination one month later the prognostic importance of definite neurological signs always associated with EEG abnormalities whereas some isolated EEG abnormalities do not have any prognostic value as far cerebral maturation is concerned. -at the final examination: the possibility after 4 months of age, of focal neurological signs not present at the earlier examinations. This study underlines the importance of precise electroclinical correlations at different developmental stages, specifically at one and four months of age in children with neonatal seizures.


[Hard-x-ray therapy. The position between orthovolt- and ultra hard ray therapy (author's transl)]. The special position of "hard-ray therapy" (RT 305, 300 kV) between the orthovolt-therapy and the ultra-hard-ray therapy is described in physical respect and clinical practicability. In comparison with the orthovolt-therapy there is an advantage in better skin tolerance, the absence of bone shadows and the possibility to increase the depth-dose up to 50%. The main indications are given in the intermediate therapy and the short distance therapy of greater tumors. The palliative deep therapy is administered under better conditions as with the conventional x-ray irradiation.


Metabolic studies on normal and pyruvate dehydrogenase deficient cultured human fibroblasts. Secondary metabolic derangements may occur in cultured fibroblasts with a defined enzyme deficiency. The metabolism of cells deficient of pyruvate dehydrogenase (5% of normal) has been studied using radioactive labelled substrates. Compared to normal control cells the activity of glycolysis was 149% (P less than 0.001), pentose phosphate shunt 144% (P less than 0.01), citric acid cycle 80% (P less than 0.002), and oxidation of acetate was 30% (P less than 0.01). The oxidation of palmitate and octanoate were not significantly different from that of control cells. Metabolic studies on fibroblasts may serve as a useful screening procedure for the detection of enzyme defects, but the results should be cautiously interpreted with respect to the localization of the primary defect.


[Use of local cobalt therapy in peripheral neuropathies associated with chronic lymphopathies (lymphoses). 2 cases with histo-immunologic and ultrastructural records]. In two cases of peripheral neuropathy, associated with a chronic lymphopathy, cobalt therapy to the lower limbs provided considerable relief of pain, with partial motor recovery. The disappearance after cobalt therapy of the lymphoid infiltrate of the peripheral nerve leads to discussion of the pathogeni role of this infiltrate. Immunofluorescent and electron microscopic studies form the basis of a discussion of the mechanism of involvement of the peripheral nerve non-secreting lymphopathies (chronic lymphoid leukaemia) and in secreting lymphopathies (Waldenström's disease).


Fibrodysplasia ossificants progressiva.

Fibrodysplasia ossificants progressiva. Two cases of fibrodysplasia ossificans progressiva are reported. Both patients were females and had suffered from the disease since birth. The characteristic anomalies of great toes and thumbs associated with multiple ectopic ossifications of the connective tissue are described. Fasciae, tendons, ligaments, and joint capsules of the proximal parts of the extremities and the dorsal aspect of the trunk were involved. The muscle atrophy was probably a secondary phenomenon.


Effect of gold on progression of erosions in rheumatoid arthritis. Better results with early treatment. The advance of radiological destruction in 57 patients with definite rheumatoid arthritis was observed for 5-6 years. In all patients gold treatment was started 2-36 months after the onset of the disease. In 18 patients gold was discontinued because of side-effects of other reasons before reaching the total dosage of 500 mg, while the remaining 39 patients received a mean dose of 2030 mg of natriumaurothiomalate. The advance of the radiological destruction was statistically significantly less marked in patients treated with the full gold therapy. The earlier the treatment was initiated, the better was the result.


[Evolution of urinary tract tuberculosis in Switzerland during the last 18 years: respective diagnostic importance of radiology and bacteriology]. In Switzerland as in other European countries, the incidence of urinary tuberculosis remained stable during the period 1957-1974, whereas a sharp fall in pulmonary tuberculosis was observable. The radiologic and bacteriologic findings in 125 cases personally observed over the last 18 years are presented.


[Acid production and the need for bicarbonate in diabetic acidosis]. In a study of 54 patients with diabetic keto-acidosis with pH on admission less than or equal to 7.1, the amount of bicarbonate (HCO3-) necessary to correct the acidosis is compared to the amount predicted by the formula HCO3- (MEq) = 0,3 X body weight (kg) KG) X delta base excess (mEq/l). HCO3- requirements vary widely among patients. In addition, whenever HCO3- is given within 1-2 h the requirement may be inferior to the value calculated, whereas with slow HCO3- infusion it can be twice or three times the amount calculated. Variable HCO3- needs among subjects, and increased needs with time, are due to acid production which may exceed 100 mEq/h, especially in young patients. The amount of HCO3- required is determined not only by the severity of acidosis but also by net acid production, which may vary widely. The assessment of acid-base balance during treatment is useful in evaluating the amount of acid produced and hence the precise need for HCO3- replacement.


Expression in Escherichia coli of a chemically synthesized gene for the hormone somatostatin. A gene for somatostatin, a mammalian peptide (14 amino acid residues) hormone, was synthesized by chemical methods. This gene was fused to the Escherichia coli beta-galactosidase gene on the plasmid pBR322. Transformation of E. coli with the chimeric plasmid DNA led to the synthesis of a polypeptide including the sequence of amino acids corresponding to somatostatin. In vitro, active somatostatin was specifically cleaved from the large chimeric protein by treatment with cyanogen bromide. This represents the first synthesis of a functional polypeptide product from a gene of chemically synthesized origin.


Hominoid enamel prism patterns.

Hominoid enamel prism patterns. Analysis of enamel prism patterns in a selected series of extant hominoids reveals that pongids have a pattern distinctively different from that of Homo sapiens. The pattern for a Miocene hominoid, Ramapithecus, is very similar to that seen in Homo sapiens. The finding allows a new approach to the evaluation of isolated teeth.


Mechanism of suppression in Drosophila: control of sepiapterin synthase at the purple locus. The amounts of sepiapterin and red pteridine eye pigments (drosopterins) in Drosophila melanogaster are known to be reduced in the purple mutant and restored to normal by a suppressor mutation. We show here that sepiapterin synthase activity is 30 percent of normal in pr and prbw, two naturally occurring alleles of purple, and is restored to nearly normal levels by the suppressor su(s)2. A heterozygote of two newly induced alleles of pr has even lower enzyme activity (less than 10 percent). The sepiapterin synthase activity is proportional to the number of wild-type pr alleles in flies when one and two copies of the allele are present and is higher in three-than in two-dose flies. We hypothesize that the purple locus may be a structural gene for sepiapterin synthase in Drosophila.


Characterization of bacterial growth by means of flow microfluorometry. By means of flow microfluorometry, the protein and nucleic acid contents of individual bacterial cells may be measured at the rate of several thousand cells per second. Accumulation of such information over a few minutes yields the composition distribution of the microbial population. These distributions have been determined at different times during batch growth of Bactillus subtilis, and the results indicate that the variance of cell composition decreases as the population passes through the exponential into the stationary phase. The relative abundance of endospores and vegetative cells as well as the protein distributions of these subpopulations may be readily determined from flow microfluorometry data. Experimental access to such details of microbial population dynamics should foster improved understanding of cell growth, spore germination, and spore formation kinetics.


Effects of malnutrition and hyperalimentation on wound healing. The effects of malnutrition and hyperalimentation on wound healing were studied in rats. Progressive weight loss occurred in rats given a protein-free diet, and there was a significant reduction in the mechanical strength of sutured skin and abdominal wounds in rats starved of protein for seven weeks. There was also a significant, but less pronounced, reduction in the tensile strength of colonic anastomoses in severely malnourished rats. Malnourished rats given oral supplements of amino acids for seven days before and after operation had a consistently positive nitrogen balance, and these rats had a significantly higher daily caloric intake than did untreated and normal rats. Amino acid therapy was associated with a significant improvement in the tensile strength and collagen content of abdominal wounds, but it had no measurable effect on the healing of skin wounds or colonic anastomoses. The results suggest that visceral and parietal tissues do not respond in a uniform manner to malnutrition or hyperalimentation, and further studies are required to determine whether or not hyperalimentation has a useful role in the enhancement of wound healing in malnourished subjects.


Ruptured bilateral synovial cysts in presumed gonococcal arthritis. A man with gonococcal urethritis who developed septic arthritis of both knees is described. The arthritis was complicated by rupture of bilateral synovial cysts. A rise in serum gonococcal complement-fixation antibody titer was demonstrated. Complement-fixing gonococcal antibodies with a high titer were observed in this synovial fluid. The patient responded well to antibiotic treatment and there was no permanent damage to his knee joints.


Gonococcal endocarditis.

Gonococcal endocarditis. Three cases of endocarditis caused by Neisseria gonorrhoeae involving the aortic, mitral an tricuspid valves are reported. Two cases in young women, following syndromes suggestive of gonococcal arthritis, presented as acute endocarditis and were fatal. The male patient experienced a subacute course, and the diagnosis was suggested by finding an extremely high level of antigonococcal antibody. This old, though now rare, disease should be considered in the differential diagnosis in patients with histories of gonococcal illness and with findings of bacterial endocarditis.


Teratogenic effects of excess glucose on head-fold rat embryos in culture. Rat embryos explanted at nine and one-half days of gestation (early head-fold stages) were cultured for 48 hours in rotating bottles containing rat serum and a gas phase. Addition of 12-15 mg/ml of D-glucose to the culture medium resulted in severe abnormalities and retarded development in a high proportion of embryos, whether or not the osmolarity increase brought about by the addition of glucose was corrected. The raised osmolarity, however, increased the frequency and severity of malformations observed. L-glucose produced no abnormalities, though embryonic development was retarded.


Genetically mediated induction of drug-metabolizing enzymes associated with congenital defects in the mouse. Various polycyclic aromatic compounds induce certain monooxygenase activities, including aryl hydrocarbon (benzo[a]pyrene) hydroxylase (EC 1.14.14.2), and cytochrome P1-450 in the liver and many nonhepatic tissues of the mouse. This induction process is controlled by the Ah locus. Genetic differences that have been shown in the past to be associated with the Ah locus include an increased susceptibility to chemical carcinogenesis, mutagenicity in vitro, and drug toxicity--manifested as hepatic necrosis, aplastic anemia, or shortened survival time. Pregnant mice received a single injection of 3-methylcholanthrene or 7,12-dimethylbenz[a] anthracene between day 5 and day 13 of gestation, and the uterine contents were examined on day 18. Striking increases were observed in the incidence of MC-1 and DMBA-induced resorptions and congenital malformations in the aromatic hydrocarbon "responsive" C57BL/6N inbred strain, and of DMBA-induced resorptions in the "responsive" C3H/HeN and BALB/cAnN strains--when compared with the similarly treated genetically "nonresponsive" AKR/N strain. These data suggest but do not prove that an association exists between the Ah locus and developmental toxicity, i.e., teratogenesis. Although numerous teratogenic differences among inbred mouse strains have previously reported, this study is unique in that the genetic differences in teratogenicity observed were predicted in advance on the basis of known differences among these strains in polycyclic hydrocarbon metabolism regulated by the Ah locus.


[Comparative studies on the effect of injections of copper in cattle showing low blood copper concentrations (author's transl)]. On a number of farms on which the young stock showed symptoms of copper deficiency, copper was injected in the form of the following compounds: Biodalbene, Robasfer and Coprin. The effects of the agents administered on the copper status of the animals were compared. This showed that there only is an effect when the concentration of copper in the blood is low (less than or equal to 50 mg/l. of blood serum). The most satisfactory results were obtained by administration of Coprin (100 mg as copper-calcium edetate) followed by Robasfer (40 mg. of copper at the recommended dosage of 25 ml), administration of Biodalbene failing to produce any improvement in copper status, which hardly could be expected by such low copper content (0.135 mg/ml). When there are practical objections to administering copper in the form of concentrates or top dressing to young stock, it is entirely practicable to use the compounds Coprin and Robasfer for this purpose.


Foetal accumulation of [14C] carbaryl in rats and mice. Autoradiographic study. Pregnant female rats and mice (18th day) received orally 10 mg/kg of 1-naphthyl-N-methyl-[14C]-carbamate (carbaryl), an anticholinesteratic drug. Animals were sacrificed 1, 5, 8, 24, 48, 72 and 960 h after administration and whole-body autoradiography was performed. Autoradiograms of the uterine cavity indicate a placental transfer and a foetal fixation of [14C] carbaryl metabolites. 14C-activity can be clearly seen in the foetus from the fifth hour; it persits till birth. We found 14C-activity in mice 60 h after birth. In both species there are some sites of accumulation in the foetal tissues, mainly in the eyes, central nervous system and liver.


[Radiation therapy of renal carcinoma: investigations and results (author's transl)]. Between 1969 and 1975, 93 patients were irradiated because of renal carcinoma, most of them after surgical treatment. The 5-year survival rate was 71%; in 56% of the cases no symptom suggested metastasition or recurrence. Invasive growth into a vein was ascertained histologically in a high percentage but did not cause significant alteration of postoperative irradiation results. The evaluation reveals that megavoltage irradiation distinctly improves the prognosis after nephrectomy in comparison with sole radical operation of malignant renal tumors. In many cases radiation therapy of solitary metastases from hypernephroma may be utilized with curative intention.


["Super stuff" as bolus in radiotherapy (author's transl)]. The use of bolus materials for a tissue-equivalent field compensation is discussed and the application of compensation filters for high-energic radiation is stressed. The properties of "Super Stuff", which is a collodial, tissue-equivalent bolus, are described and compared with those of other materials such as polystyrene, plexiglas and water. The universal possibilities of applying "Super Stuff" as field compensating material are demonstrated on a practical example in the field of the kV therapy.


The influence of thiamin deficiency on the metabolism of the oral contraceptive mestranol [3-methoxy-17-ethynyl-1,3,5(10)-estratrien-17 beta-o1] by female rat liver enzymes. Hepatic microsomes from female rats fed a thiamin deficient diet for three weeks had approximately three times the capacity to metabolize mestranol as microsomes from similar rats fed a diet rich in thiamin. The incremental addition of thiamin to the diet depressed mestranol O-demethylation, NADPH cytochrome c reductase, and cytochrome P-450 content in a dose related manner up to 2 microgram thiamin per gram of feed. Pair-feeding experiments indicate that thiamin ingestion is responsible for the depression of mestranol O-demethylation and NADPH cytochrome c reductase activity while carbodhydrate ingestion is responsible for the decrease in cytochrome P-450. The absorbance spectra generated by the binding of ethylisocyanide to microsomes yield data which suggest that there are no qualitative alterations in cytochrome P-450 due to diet.


Serum estradiol and progesterone during pregnancy and the status of the corpus luteum at delivery in cynomolgus monkeys (Macaca fascicularis). Levels of estradiol and progesterone in peripheral serum of seven cynomolgus monkeys (Macaca fascicularis) were measured from about the 30th day of pregnancy until parturition. Although the pattern of each steroid in circulation differed somewhat from the respective patterns in rhesus monkeys (Macaca mulatta), there were basic similarities. On the day of delivery, the corpus luteum was excised and in vitro incubation of dispersed luteal cells was performed. Isolated luteal cells produced progesterone under control conditions and responded to the addition of HCG with enhanced steroidogenesis. Accordingly, "rejuvenation" of the corpus luteum may occur during advanced gestation in cynomolgus monkeys. These findings, along with establishing the efficacy of the Subhuman Primate Pregnancy Test kit to diagnose pregnancy in this macaque, extend previous evidence for utility of cynomolgus monkeys as a primate model for study of steroid hormones in pregnancy.


[Transformation of the temporomandibular joint in the treatment of sagittal bite anomalies]. The results from distocclusion and mesiocclusion treatments were radiologically evaluated in 89 patients. In two experiments, mesiocclusion and distocclusion were produced in monkeys by means of cemented inclined planes. The transformations thus achieved were evaluated by radiography, histology and craniometry. The treatment of distocclusion results in an increase in size of the mandible, of the angle of the mandible, and of the lower third of the face. The head of the condyle erects itself. Reactive tissue changes (activation of the osteoblasts and osteoclasts, accelerated ossification of the cartilage) were seen in the dorsal part of the head of the condyle. Thus, the theory of Breitner is not confirmed. There were no resorption phenomena at the articular eminence and in the anterior part of the head of the condyle, and no so-called pressure and traction zones.


[Structural changes in the tibial bones from an excessive load]. 80 cases of pathological reconstruction of the tibia in young men at the age of 18--20 are described. The pathology developed as a result of intense regular physical exercise. In 53 patients the process was localized in the upper third of the tibia, in 20--in the middle third and in 7--in the lower third of the bone. In 6 cases the fracture of the tibial proximal metaphysis happened against the background of pathological reconstruction of the tibia; 3 of them sustained simultaneously a fracture of the fibular head. Some recommendations of practical importance are suggested.


Gynecologic pathology in the rhesus monkey (Macaca mulatta). II. Findings in laboratory and free-ranging monkeys. The most prevalent findings in reproductive tracts of 38 laboratory and 17 free-ranging Rhesus female monkeys were vaginitis, cervicitis, metritis, pelvic endometriosis and uterine adenomyosis. Several monkeys had cervical dysplasia and one had a serous cystadenoma. The findings in the two groups were similar although prevalence for several diseases differed. There was a significant relationship between the occurrence of vaginitis, metritis, adenomyosis and endometriosis and gravidity, time since last pregnancy, number of matings, hysterotomies, reproductive ability and reproductive status.


[Immunologic and epizootologic studies of toxoplasmosis in sheep]. A total of 698 blood serum samples from sheep in various regions of the People's Republic of Bulgaria were examined throught the indirect hemaglutination micromethod. Two-hundred and seventeen proved positive for toxoplasmosis. Those of the samples that were taken from ewes that had miscarried and reacted positively were considerably more--43.3 per cent--than those that were taken from ewes with normal lambing and reacted positively--21 percent. Besides, toxoplasmosis was shown to be more widely spread among sheep in the mountainous regions (40.3 per cent) than in sheep from the plain regions (18.3 per cen). Four cystogenic strains of Toxoplasma were isolated from fetuses of nine ewes that had miscarried. Out of 493 sheep investigated in Czechoslovakia 33.3 per cent were positive by the indirect hemagglutination reaction, 29.7 per cent were positive by the indirect fluorescence reaction (RIF), and 11.6 per cent were positive by thr microprecipitation agar gel reaction (MPA). States is the epizootiologic and economic importance of the problem.


[Distribution, species composition and seasonal dynamics of ticks of the Ixodidate family in northwest Bulgaria]. It has been established that a total of 7 species of Ixodes ticks parasitize in farm animals in the northwest region of the country. The prevailing species is Rh. bursa, which constitutes 67.07 per cent of all ticks that have been collected and plays a basic role in the epizootiology of hemosporidioses. Described are the basic biotopes of the prevailing species. It has been demonstrated that altitude influences the durat-on of the seasonal activity of the parasites as well as the period during which farm animals harbour the parasites.


[Phage diagnosis of strains of Bacillus cereus isolated from food products]. A total of 80 cultures of Bacillus cereus, isolated from food products, were studies to establish the behaviour to specific phages or the CAM set and the presence of lysogeny. A modern bacteriophage method was tested for the first time in the differentiatons of Bacillus cereus, which was so far studied mainly in the differentiation of Bacillus anthracis. Results showed that bacteriophagy with specific type phages as a method, though not absolutely precise, is dependable for the differentiation of Bacillus cereus. It can be used as a fast adjunct technique in the determination of B. cereus from the view point of its species. No lysogenic strains were established in the cultures investigated.


Epidermal intercellular relationships during carcinogenesis and cocarcinogenesis as revealed by scanning electron microscopy. Investigations with the scanning electron microscope were carried out on the skin of 80 NMRI mice after treating them with small doses of the carcinogenic substance DMBA and the cocarcinogenic agent TPA, respectively. The results were correlated with histologic, transmission electron microscope and autoradiographic observations. The epidermis of TPA-treated animals was markedly hyperplastic with an orderly arrangement of cell layers. Autoradiographically only the basal cells were heavily labelled. With the scanning and transmission electron microscope a reduced number of intercellular connections and dilatation of the intercellular spaces could be detected. After treatment with DMBA the epidermis was only moderately hyperplastic but severely dysplastic with 3H-thymidine-labelled cells in the upper layers. The most characteristic findings were the loss of the intercellular connections, especially the lateral ones, and a pronounced dilatation of the intercellular spaces. The results obtained with the scanning electron microscope were quantified using morphometrical methods.


DNA synthesis in the ventricular myocardium of young rats exposed to intermittent high altitude (IHA) hypoxia. An autoradiographic study. Intermittent high altitude (IHA) hypoxia (7000 m) increased the wet weight of the right ventricular myocardium of 30-day-old rats after two 4 h/day exposures. During the same period the number of DNA-synthesizing nuclei of both muscle and non-muscle cell types increased proportionally. After 4 such exposures to hypoxia the number of 3H-thymidine-labelled nuclei in both cell types increased further. In addition, the number of labelled nuclei increased significantly in the yet un-enlarged left ventricle. While there was no difference in the number of DNA-synthesizing cells between the right and left ventricles in control animals, a significant increase in the number of cells involved in DNA synthesis in the right ventricle was found in both groups of animals exposed to IHA hypoxia. These results show that DNA synthesis in myonuclei of the ventricular myocardium can be stimulated in 30-day-old rats, i.e. at the very end of the weaning period.


Lysosomal degradation of bile deposits in cholestasis. An ultrastructural and cytochemical study. Deposits of bile in the cytoplasm of hepatocytes from six patients with cholestasis were studied by electron microscopy and ultrastructural cytochemistry. The deposits were identified in vacuoles of varying size and complexity. The demonstration of acid phosphatase activity in these vacuoles suggests that lysosomes participate in the elimination of bile deposits retained in hepatocytes.


The proliferation of chondrocytes and pannus in adjuvant arthritis. Cell proliferation in the pannus formation of adjuvant arthritis was studied by autoradiography. It was found that after day 9 an increased cell proliferation starts in the joint capsule recessus and synovial villi on the injected side. From these proliferating cells a pannus, which during the first phase frequently consists only of few cell layers, extends over the cartilage surface. With advancing disease the thickness of the pannus increases and further centripetal growth may cause the entire cartilage surface to be covered. This proliferating pannus tissue may invade the cartilage and destroy it. Since in this area of destruction labelled cells are frequently present, it may be assumed that proliferating cells with a high enzyme content are particularly responsible for the immediate degradation of cartilage. No involvement of chondrocytes in pannus formation was confirmed by the methods employed. There was neither increased proliferation of surface chondrocytes nor increased proliferation of chondrocytes in the depth of cartilage.


The effect of testosterone and cadmium on the rat lateral prostate in organ culture. Organ culture of rat lateral prostate was performed in the presence of testosterone and cadmium. Maintenance of epithelial cells did not occur even in the presence of the androgen, but basal cells were stimulated and replaced original epithelium. Testosterone alone caused a partial differentiation of these basal cells. Cadmium alone was found to enter the epithelial and basal cells and subsequently cause necrosis. The metal was subcellularly located in the nucleus and within cytoplasmic organelles. Cadmium appears to compete with zinc in cultured lateral prostate and affects the differentiation and maintenance of the epithelial growth.


The effect of cadmium administration in vivo on plasma testosterone and the ultrastructure of rat lateral prostate. Electron microscope microanalysis, atomic absorption analysis and ultrastructural survey were used to investigate the effects of parenteral cadmium administration on the lateral prostate of rats. Early fine structural changes in the epithelial cells of the prostatic tissue were associated with the detection of cadmium in the cellular organelles and alteration of the subcellular distribution of zinc. Involutionary changes appeared at later stages and differed from the usual castration effects. Basal cells did not regress with the altered physiological conditions but appeared to proliferate in the presence of cadmium. The observations are discussed in relation to the normal mechanisms which control the maintenance of the prostate gland.


Selection of Ehrlich tumor cells in different phases of the cell cycle by ficoll gradient centrifugation. Mouse Ehrlich ascites tumor cells were centrifuged at low speed on a linear Ficoll gradient. Cells from different fractions of the gradient were collected separately and analysed by cytological and cytochemical methods (DNA content, mean volume and number of cells). Nearly pure populations of cells in G1 or S were selected. A heterogeneous population containing 70% G2 and mitotic cells was also isolated. No ultrastructural alterations were detected in the cells after centrifugation. Selected G1 cells were cultured in vitro, their kinetic parameters were measured and compared with those of the original population. No difference was observed as far as the duration of the cycle of these cells is concerned.


Fine structural and ultracytochemical studies on the lymphocytes in three types of genetic mucopolysaccharidoses. Lymphocytes from 6 patients with 3 types of genetic mucopolysaccharidoses (Hurler's syndrome, Hunter's syndrome and Morquio's syndrome) contained numberous vacuoles in their cytoplasm. The size of the vacuoles ranged from approximately 300 nm to 750 nm. The percentage of the lymphocytes with vacuoles varied from 10% to 38%. The vacuoles showed acid phosphatase activity, which indicated their lysosommal nature. Staining with dialyzed iron solution usually localized acid mucosubstance in the peripheral region of these vacuoles after glutaraldehyde fixation. Ferritin and horseradish peroxidase were observed in the vacuoles after incubation of the patient's lymphocytes with these tracers. This finding indicates the participation of endocytosis in the formation of these vacuoles.


Studies on the possible influence of the so-called wound healing reaction on DNA synthesis in organ culture. Tissue sectioning is a necessary preliminary step in the preparation of organ culture explants. The real extent of tissue damage in the "wound healing reaction" can be assessed by DNA isotopic labeling. The differential count of labeling indices between epithelial structures located at the margin of the explants and similar structures near the center was used to study the influence of tissue damage on DNA synthesis. Our results suggest a time-related influence of wound healing on labeling indices. This reaction has to be taken into account when DNA synthesis is used as an indicator of hormonedependency in vitro.


Scanning electron microscopic study of the effect of vinblastine on podocytes of rat kidney. Loss of cytoplasmic microtubules was induced in rat renal podocytes by intravenous administration of the microtubule poison, vinblastine sulfate. Scanning electron microscopy was used to study the shape exhibited by podocytes 2, 8, or 12 h after initiation of vinblastine treatment. The podocytes of all vinblastine-treated rats possessed focal enlargements of cellular processes. At 8 and 12 h the focal enlargements were more abundant and often larger than those seen at 2 h. In addition, at the longer exposure times many cellular processes were smaller in diameter than comparable processes of control animals. There was no evidence that a loss of pedicel organization occurred with any of the three treatment times studied. The results suggest that in the absence of microtubules a redistribution of cytoplasm occurred within podocyte processes, resulting in the accumulation of cytoplasmic material at certain sites and a concomitant narrowing of the diameter of processes in other regions. Thus, intact microtubules appear to be essential for normal podocyte shape.


Enteroglucagon and substance P-like immunoreactivity in argentaffin and argyrophil rectal carcinoids. A specific immunofluorescence for enteroglucagon or substance P or for both hormones was demonstrated in nine out of 12 examined rectal carcinoids. One tumor was argentaffin, contained ultrastructurally pleomorphic granules of the entero-chromaffin cell type, and showed immunofluorescence for substance P. The rest were non-argentaffin but were argyrophil with the Grimelius technique and contained round granules. The argyrophil carcinoids were immunoreactive to one or both hormones in eight cases and not fluorescent in three cases. In two of the non-argentaffin carcinoids a small number of argyrophil cells was found with the method of Sevier-Munger.


Long-term results of deep defects in articular cartilage. A scanning electron microscope study. Core defects produced in the medial femoral condyle of the rabbit were studied by scanning electron microscopy and light microscopy over a period of 2 years. In some cases the defect was filled by hyaline articular cartilage with a fairly smooth surface, but in others the tissue was markedly fibrillated and resembled fibrous tissue and fibrocartilage. Appearances suggesting disintegration of the newly formed cartilage were seen in some cases. It would appear that a continuation of this process can lead to the exposure of subchondral bone. In one instance no repair tissue or new cartilage could be identified but the surrounding old cartilage had formed a shelf over the defect. The cartilage surrounding the defect was either normal or showed superficial fibrillation, and/or flow formation, and/or fissures.


Early post-mortem change of the crista ampullaris. A light and electron microscopic study of the Guinea-pig. Post-mortem change (autolysis) of the sensory and the secretory epithelia was studied by means of the light and the electron microscope. The first ultrastructurally recognizable sign of autolysis occurred 10-15 min after death in the mitochondria of the hair cells and their adjacent nerve endings. The morphology of hair cells was occasionally well preserved 30 min post-mortem, but after 90 min or more autolytic changes were invariably severe. The secretory epithelium, however, was considerably less affected by autolysis than the hair cells during the first 5 h after death.


Acute distal intestinal obstruction in gnotobiotic rats. Intestinal morphology and cell renewal. 1. Complete mechanical obstruction of the distal small intestine was produced in gnotobiotic rats. 72 h after the operation small intestinal morphology and epithelial cell renewal were investigated proximal and distal to the site of obstruction. 2. Proximal to the site of obstruction there were minor changes in villus height, base length and in villus cell number, a large increase in depth and diameter of the crypts and an approximately threefold increase in cell renewal. 3. Distal to the site of obstruction there were no differences between the intestines of rats with obstruction and controls. 4. The apparent lack of secretion by the goblet cells and the reduced number of intraepithelial leucocytes suggest that the barrier function of the small intestine is impaired in obstruction.


Nafenopin-induced proliferation of peroxisomes in the small intestine of mice. The effect of nafenopin on the epithelial cells of the small intestine of mice was studied. After 17 days the control and nafenopin-treated groups were sacrificed. The tissues were incubated in alkaline DAB medium. Ultra-thin sections of small intestinal tissue from both groups were examined by electron microscopy. Electron micrographs were prepared and examined stereologically so that any morphologic differences in the epithelial cell peroxisomes and mitochondria between the experimental and control groups could be evaluated quantitatively. In the nafenopin-treated group proliferation of peroxisomes occurred, as indicated by significant increases in volume, and surface and numerical density of these structures compared with controls. No such alterations were found in the mitochondria. Our results show that the response of small intestinal epithelial cells to nafenopin is analogous to that produced in hepatocytes by the same drug. Hepatocyte peroxisomes are supposed to be involved in lipid metabolism and it seems that small intestinal epithelial peroxisomes play a similar role.


Effects of erythrocyte lysate and erythrocyte-conditioned medium on erythroid cells in vitro. A component of erythrocyte-conditioned medium has been shown to inhibit the incorporation of tritiated thymidine into erythroblasts from fetal mouse liver, proliferating in vitro. This component, however, has no detectable effect on the growth of colonies of erythroid cells stimulated to grow in viscous culture media by the hormone erythropoietin. Erythrocyte lysate and preparations of haemoglobin derived from the lysate increase the number and size of the colonies growing in vitro. Results are discussed in terms of possible control mechanisms in erythropoiesis.


Increased capillary permeability in muscularis layer of rat intestine caused by kidney extract. Kidney extract and synthetic angiotensin II were injected into bilaterally nephrectomized rats in dosages capable of raising the mean arterial pressure by about 20 mmHg. Changes in ultrastructure and permeability for ferritin molecules were then examined in capillaries located in muscularis layer of the intestinal walls. Kidney extract with a high renin content was obtained from the renal cortex of rats by means of stepwise centrifugation methods. Animals injected with saline served as controls. In rats receiving kidney extract tissue edema was observed in the spaces around the blood and lymphatic capillaries. In these spaces ferritin molecules accumulated in high concentration indicating plasma protein leakage. Ferritin molecules within the endothelium were restricted within plasmalemmal vesicles, but were not found within interendothelial junctions or within the cytoplasmic matrix. Morphometric analysis of vesicular transport in the endothelial cells revealed a significant increase in labeling rate for the vesicles with ferritin molecules. These results suggest that the kidney extract contains substance(s) which increase capillary permeability for plasma proteins at least via increased vesicular transport, resulting in tissue edema.


Development of Rh-specific maternal autoantibodies following intensive plasmapheresis for Rh immunisation during pregnancy. Two cases of autoantibody formation following large volume plasmapheresis for rhesus immunisation during pregnancy are described. In each case the autoantibody was directed against the Rh complex but showed a preference for G-positive cells. It is postulated that repeated plasmapheresis in the presence of persistent antigenic stimulation has removed a feedback inhibition of the immune response. The specificity of the alloantibody has broadened resulting in cross-reactivity against self-antigens. The possible implications of these cases in relation to autoimmunity are discussed.


Caprylate-dependent auto-anti-e.

Caprylate-dependent auto-anti-e. A caprylate-dependent autoantibody with specificity for the e antigen of red cells is described. The antibody was completely inactivated by 2-mercaptoethanol and was probably of the IgM immunoglobulin class. The antibody had no apparent specificity for albumin. Reactivity of the described antibody may depend upon conformational change of red cell Rh antigen by caprylate.


[Survival of tick-borne encephalitis complex viruses in a brain cell culture from suckling mice]. The evidence of long-term survival of the tick-borne encephalitis complex viruses in primarily trypsinized brain cells of suckling mice inoculated in vivo is presented. The viability of the brain cell cultures from suckling mice inoculated with an attenuated strain was shown to be higher than that of a similar culture of the brain cells from suckling mice infected with a virulent strain. The infectious virus could be recovered for over 200 days of the existence of these cultures. The experimental results appear to be another confirmation of the capacity of viruses of the tick-borne encephalitis complex, particularly of the attenuated strains, for persistence.


[Antigenic activity of a concentrated and purified cultured antirabies vaccine from the Vnukovo-32-107 strain]. Humoral response (virus-neutralizing antibody production) to immunization with inactivated 30-fold concentrated and purified tissue culture rabies vaccine was studied in monkeys and human volunteers. Two doses of the preparation spaced 20 days apart and given intramuscularly or intradermally to monkeys induced in them much more intensive antibody production (4--213-fold by titer) than 6 daily injections of unconcentrated vaccine. In 10 human volunteers immunized with 1.5 ml doses of the concentrated vaccine intramuscularly twice 20 days apart antibody titers 40 days after immunization varied from 1:79 to 1:6250 (average 1:1067). In another group of 10 human volunteers immunized intramuscularly with the concentrated vaccine 3 times at 0, 1st and 20th day, antibody titers 40 days after immunization were 1:112--1:3273 (average 1:508). These values are significantly higher than the average titers in humans vaccinated with unconcentrated tissue culture of brain vaccine of Fermi type. The concentrated vaccine proved to be a preparation of low reactogenicity: no systemic reactions were observed among vaccinated volunteers; 4 out of 20 volunteers had a mild, transient (1 day) local reaction (hyperemia of less than 1.5 cm in diameter).


[Titration of the antibodies to the Crimean hemorrhagic fever virus in a drop of the cell suspension from infected tissue cultures by means of indirect immunofluorescence]. A comparatively simple method has been developed and tested for the detection and titration of antibody to Crimean hemorrhagic fever virus (CHF) by indirect immunofluorescence on slides with previously prepared acetone-inactivated virus in drops of cell suspension from infected BHK-21 and 6619 cell cultures. The antibody titers determined by the indirect immunofluorescence procedures were 4- and 8-fold higher than those determined by the complement-fixation test. This opens the possibility of using non-infectious antigens of cell suspensions for detection or titration by the FA procedure of antibody to CHF virus which may be of importance to diagnostic laboratories which have no conditions for work with live virus.


Metabolism of arylacetic acids. 1. The fate of 1-naphthylacetic acid and its variation with species and dose. 1. [Carboxy-14C]-1-Naphthylacetic acid has been administered to man, 6 primate species and 4 other mammalian species and the urinary metabolites examined by radiochromatogram scanning and reverse isotope dilution. Animals all received a dose of 100 mg/kg and man received 5 mg, orally. 2. Most species excreted at least 60% of the 14C in the urine in 48 h. Unchanged acid was a minor (0-17% dose) excretion product in all species except the cynomolgus monkey (35%). 3. In man, in 24 h 95% of 14C was excreted as 1-naphthylacetyl-glucuronide and 5% as 1-naphthylacetyltaurine. 4. 1-Naphthylacetylglucuronide was the major excretion product in all species except the bushbaby (21% dose) and the cat, which did not form this conjugate. 5. 1-Naphthylacetylglutamine was formed only by the cynomolgus, squirrel and capuchin monkeys and marmoset, and in no case accounted for more than 3% dose. 6. 1-Naphthylacetylglycine was found in the urines of 4 primate and 3 non-primate species, and was the major metabolite in the squirrel monkey, bushbaby and cat. 7. 1-Naphthylacetyltaurine was excreted by all species except the rabbit and the fruit bat. It was a major excretion product in the squirrel and capuchin monkeys, the marmoset and the cat. 8. The influence of dose on the pattern of metabolism and excretion of 1-naphthylacetic acid has been investigated in the rat.


Metabolism of arylacetic acids. 2. The fate of [14C]hydratropic acid and its variation with species. 1. (+/-)-[methyl-14C]-Hydratropic acid was administered to man, rhesus monkey, cat, rabbit and fruit bat. 2. All species excreted 60-100% of administered 14C in the urine in 24 h, and unchanged hydratropic acid accounted for 0-17% of the dose. 3. In man, the urinary 14C consisted of a very small quantity (1%) of unchanged hydratropic acid with the remainder as hydratropylglucuronide. 4. Hydratropylglucuronide was the major urinary excretion product in the 4 animal species, while the glycine conjugate was present in the urine of cat and rat. Additionally, cats excreted the taurine conjugate of hydratropic acid. 5. Bile-duct cannulated rats excreted 20-30% of an injected dose of [14C] hydratropic acid in the bile in 3 h mainly as hydratropylglucuronide.


Sodium chloride stimulated respiration of Anacystis nidulans. With certain salts a stimulation of respiration of the blue-green alga Anacystis nidulans was found in the dark. The stimulation was observed only at high concentrations (10(-2)M--10(-1)M). NaCl or LiCl are the most effective salts and on addition the increase of the respiration is about 2.5fold. Li is assumed to function as a substitute for Na. Potassium salts, except KCl, are ineffective. The order for the effectiveness is: NaCl greater than NaNO3, Na2SO4 greater than KCl greater than KNO3, K2SO4 (=zero). Accordingly, the cation Na+, and to a less degree the anion Cl- are responsible for the stimulatory effect. K, which is ineffective, is passively accumulated by Anacystis according to the membrane potential. Na is actively extruded. At 0.1 M external NaCl, the passive influx of Na is high, but even then it is balanced by an active efflux. This increases the energy consumption of the cells and leads to a stimulated respiration. With DCCD (N,N'-dicyclohexylcarbodiimide) or NEM (N-ethylmaleimide), the Na efflux is inhibited, simultaneously the stimulation of respiration is abolished and the passive influx of Na becomes detectable. At 0.1 M NaCl, the passive influx of Na measured in presence of DCCD is 5 x 10(-6) moles Na/min and ml packed cells. In absence of DCCD on addition of 0.1 M NaCl the extra oxygen consumption is 2 x 10(-6) moles O2/min and ml cells. This may prove that the stimulation of respiration is mainly caused by the active Na extrusion.


The organization of agonistic relations within two captive groups of Java-monkeys (Macaca fascicularis). The paper offers a detailed quantitative descripition of the distribution of agonistic activities over the members of two groups of Java-monkeys (Macaca fascicularis). These groups lived in captivity and were well-established: i.e. they had an extensive network of genealogical relationships. The study pays special attention to agonistic interactions with three or more participants. Its main purpose is an analysis of the way dyadic agonistic relations (e.g. dominance relations) are affected by third group members and the relations among these. The paper presents data on the ontogeny of 'dependent dominance', the 'control role' of the alpha-male, and the functions of different types of alliances.


Studies on the fine structure of corynebacterium diphtheriae-granules. The seemingly homogeneous metachromatic and electron-scattering granules of Corynebacterium diphtheriae have two structural components as revealed under conditions of low beam load and by use of ribonuclease. They contain high percentages of P and Ca. Findings point to participation of ribosomes and intracytoplasmic membranes in the formation of the granules.


Factors influencing the assessment of the pseudomonacidal activity of disinfectants by a quantitative suspension test. I. Influence of the growth conditions of the test organism. A matter of special concern in disinfectant testing is the preparation of the bacterial suspension that shall be exposed to the action of the disinfectant. In the present paper attention is drawn to three details of the testing method being determinative for the resistivity of the test organism and for the degree of standardization of the test results. - In the first place the influence of the nutrient medium used in the cultivation of the test organism has been investigated. Sixteen culture media (Table 1) have been compared. The resistance of Pseudomonas aeruginosa to phenol depends on the formulation of the preparatory medium: significantly more bacteria survive if the test organism is grown on the nutrient agar following the German pharmacopoeia (Table 2). Further the author has investigated the effect of the temperature and the length of the initial culture incubation period (Tables 3 and 4). Here also the differences among temperatures (37, 32 and 22 degrees C) or incubation periods (48, 24 and 18 h) are statistically significant. The highest numbers of survivors are found when the initial culture is incubated at 37 degrees C and for 48 h. Whereas the resistance of the test culture is determined by these three factors, the variability of the test results is not. The coefficients of variation calculated for the different initial culture media, the three incubation temperatures or the three incubation periods show no differences among these test conditions.


Factors influencing the assessment of the pseudomonacidal activity of disinfectants by a quantitative suspension test. II. The post-disinfection recovery of surviving organisms. Bacteria which have been treated by a disinfectant may be partially damaged so that they will be able to survive and to multiply only if all environmental factors are kept as optimal as possible. Otherwise no growth at all is obtained and the disinfectant solution will be wrongly considered as active. Therefore the technique of the post-medication recovery of surviving microorganisms is a matter of great importance. Since our aim is to elaborate a quantitative test, the counting technique using pour or streak plates is investigated here. In contrast to the results of viable counts of normally cultivated P. aeruginosa (Tables 1 and 2), the colony counts of phenol-treated bacteria gain higher figures when the spread plate method is used instead of the pour plate technique (Table 3). - Out of nine solid media examined (Table 4), four culture media are considered to be superior to the others (Table 5). They are Davis Agar, the Nutrient Agar of the German pharmacopoeia, the Nutrient Agar proposed by the APHA, and Tryptone Soy bean peptone Agar. Further investigation on the influence of the recovery medium is needed since there is stated that significant differences are obtained when three preparations of the same formulation are compared (Table 6). Finally the author observed that the volume of the culture medium affects the survival rate (Table 8). The recovery of disinfectant-treated bacteria is found to be very complex; further research on this domain should be encouraged.


[Development of a new testmethod for surface disinfection procedures. III. The impression method: influence of the test surface material and the types of microorganisms on the recovery rate (author's transl)]. The preceding test results appear to favour the impression method used for the testing of surface disinfection procedures. Further investigations were concerned with the selection of a suitable germ carrier. The high recovery rate of the bacteria and the invariably uniform  quality of the germ carrier are the decisive criteria. Since a dependence on the type of germ was also to be expected, we checked Staph. aureus, Str. faecalis, E. coli, Kl. pneumoniae and P. aeruginosa for their behaviour on PVC, varnished wooden surfaces, V 2A, rough and smooth glass, resopal, ceramic tiles with dull and glazing finish as well as on plywood. The germ carriers were contaminated quantitatively, dried, sprayed with distilled water to stimulate disinfection and examined after they were allowed to react for a period of 6 hours. A set of 10 germ carriers was examined simultaneously with 10 Rodac impressions. The data were checked by variance analytical methods and evaluated on the mean (or median) values. It was found that while the initial germ number was kept equal OP tiles and V 2A steel produced the highest germ yield. Plywood proved largely unsuitable. Among the test germs, E. coli and Kl. pneumoniae had the lowest adhesion; it was inferior to that of staphylococci and pseudomonads. However, for these 4 germ types 3 impressions  per germ carrier suffice for a reliable assessment based on computations. The yield amounts to more than 90 per cent. 94 per cent of the Streptococci were also recovered with 3 impressions, but the absolute germ quantity was low. The use of this type of germ can be recommended only with reservation.


[Development of a new testmethod for surface disinfection procedures. VII. Proposal for the method (author's transl)]. Based on the findings obtained from the previous experiments (information I-VI), a proposal is made for the examination of surface disinfection procedures under conditions roughly resembling those prevailing in practice. This test allows the action of the disinfectant to be calculated, while making due allowance for the natural rate of kill. The results of three tests with a liminally effective disinfectant concentration extensively agreed with each other. This permits the conclusion that the method has reached optimal standardization.


Reactivation of the EDTA-treated arginase from rat and calf liver. 1. The anionic calf liver arginase, like the cationic rat liver enzyme, is inactivated by EDTA-treatment. The activity is fully restored by Mn2+. A smaller effect is observed with Cd2+, Ni2+ and Co2+. 2. The EDTA-inactivated calf liver arginase, unlike the rat liver enzyme, does not dissociate into subunits, and its mol.wt. (120 000) is unchanged. 3. The reactivation of rat liver arginase subunits (mol.wt. 30 000) by Ni2+ is accompanied, similarly as in the case of Mn2+, by reassociation to the form of mol.wt. 120 000, i.e. the same as for the native enzyme. 4. It is suggested that Mn2+ in arginase is bound at the active site and at the site responsible for maintenance of the oligomeric structure. In calf liver enzyme this binding site is inaccessible to the chelating agent.


Diethylpyrocarbonate and benzoquinone vapour fixation for immunofluorescence studies of non-hormone protein in frozen dried tissues. The use of gaseous (DEPC, BOV) postfixation of frozen-dried tissues for the fixation of non-hormone proteins was systematically studied. The fixation ability was tested on the "protein droplet model" i.e. the protein droplets formed in mouse liver after intravenous injection of bovine serum albumin (BSA). 1. There is no difference in the fixation ability for BSA between DEPC and BQV. 2. Both fixatives yield a very poor fixation of BSA in frozen-dried livers. In consequence, this protein is already extracted during section mounting and incubation for immunofluorescent tracing causing a strong substantial loss. 3. Remaining protein traces, however, are still immunoreactive indicating that DEPC and BQV fixation does not affect the antigenicity in considerable extent.


[Role of iron ions on tannin-iron method histochemical specificity (author's transl)]. In this work is studied the tannin-iron method specificity when the ferrous chloride is replaced by other iron compounds. Nervous tissue and rat duodenum cuts are used. Cuts were treated with tannic acid and after with FeCl3; FeCl2; FeOHCl2; FeAc2; Fe2O3; FeSO4; NH4Fe(SO4)2 or colloidal iron solution. Dilution effect from every one of aforementioned iron compounds too is studied. The obtained results with those furnished by the OTA method by using the tannic acid in identical conditions are compared. Also several treatments of blockade were carried-out. The obtained results prove that iron ions play a different role in the mucins staining than in other demonstrable substances coloration in the nervous tissue. In the same way evidences that the iron ion that joins the mucins in the tannin-iron method is the FeOH++ ion were obtained.


Histochemical study on the glycosaminoglycans (acid mucopolysaccharides) of the human coronary arteries. Investigations carried out on fetuses, children, adolescents and young adults showed that a particular histochemical pattern of the coronary intima glycosaminoglycans existed in each group of age. Beginning with childhood, a subendothelial "ground substance-rich layer" could be more clearly and constantly delineated in the thickened coronary intima. It exhibited a different chemical composition and macromolecular structural stability of its glycosaminoglycans as compared to those of the elastic hyperplastic and musculo-elastic layers. The presence of a "ground substance-rich layer" including dermatan sulfate and glycosaminoglycans resistant to hyaluronidases and chondroitinases appeared in our material as a prerequisite for the development of fatty dots and streaks. During the onset of fibrous plaques, the progressive blockade of the glycosaminoglycan acidic groups by basic proteins and the occurrence of numerous saline linkages between intimal macromolecular aggregates were the prevalent histochemical changes.


[Acid phosphatase localization in the mucous membrane of chicken large intestine (author's transl)]. In the wall of chicken large intestine, acid phosphatase was found only in the mucous membrane. It is present in lysosomes of the Golgi zone of enterocytes, in lysosomes of goblet cells, and in the specific granules of globule leucocytes. In the epithelium of the neck of caecum and of the colon the amount of acid phosphatase decreases towards the tip of the villi. Localization differences of enzyme are present in the villiless caecum bodies, where the surface epithelium and the epithelium of the intestinal glands neck lack the acid phosphatase activity. In the Lamina propria mucosae the enzyme is localized in fibrocytes occurring in abundance in the stroma of the caecum neck and colon and between the intestinal glands of the caecum body.


Cytochemical localization of acetylcholinesterase in the rat striatum. An attempt was made to determine the subcellular localization of AChE in rat striatum with several Cu-thiocholine procedures using slices of intact tissue and in isolated organelles obtained by gradient centrifugation. Regardless the method used the reaction product, indicating the localization of AChE activity shows the usual intracellular and extracellular distribution. Although AChE activity was present at the extrajunctional axolemma of the nerve endings almost no enzyme activity was observed in the junctional region either in tissue sections or on isolated synaptosomes.


The microspectrophotometric research of the content of ascorbic acid in carcinomas of the uterine cervix. Taking into consideration the fact that the ascorbic acid takes an active part in the process of growth and reproduction of the cells, the authors have undertook the microspectrophotometric research of its content in 27 different structure cancerous tumours of the uterous cervix. The result of the research showed the decrease of the quantity of ascorbic acid in cancerous tumours of the uterous cervix in compare with norm. The content of ascorbic acid in carcinomas cancerous tumours of the uterine cervix depends on the degree of differentiation and histogenesis of the neoplasm. In less differential squamous cell cancers the quantity of ascorbic acid is more than in the mature ones. The least quantity of ascorbic acid is in adenogenic carcinomas of the uterine cervix. The micro-spectro-photometric research of the content of ascorbic acid in cancerous tumours of the uterine cervix may be used as test in practical activity of the pathologoanatomist for the differential diagnostic and prognosis.


[Fluorometric determination of the quality of FITC-anti influenza conjugates (author's transl)]. A fluorometric method for the evaluation of FITC-anti influenza conjugates is described. The titre and that dilution required for the complete detection of antigens can be determined. It is possible to verify the probability of detection in per cent for any dilution stage and to compare objectively different batches. For this microtest only 0,2 ml conjugate are necessary.


[Presence of biogenic amines in the Langerhans' islets of the sand rat (Psammomys obesus) (author's transl)]. The islets of Langerhans of sand rats (Psammomys obesus) have been investigated ultrahistochemical in order to demonstrate biogenic amines. It could be found that amine containing vesicles with a diameter of 600 to 700 nm from the type of catecholamine granules exist in A-cells as well as in B-cells. Further, 2 very rare cell types not containing specific hormone granules could be found. These cells contain particles, in one case similar to catecholamine granules and in the other case representing serotonine-like granules according to their electron optical properties. It can be stated that the sand-rat belongs to the species containing amines in A- and B-cells. Moreover they contain 2 amines simultaneously. The importance of the amines for the regulation of the hormone secretion of the islets of Langerhans is discussed and the connections to the diabetes mellitus are refered to.


Quantitative determination of acid phosphatase activity detected in tissue sections according to the Burstone method. Quantitative determination of the activity of acid phosphatase detected in tissue sections using Burstone's method. The experiment was performed on inbred rats. A reaction for AcP according to Burstone was made in liver sections, incubation time was fixed experimentally. The material obtained from each animal was divided into 3 parts. One of them was used for enzymatic estimations, the 2nd for planimetry of sections, and the 3rd was eluted by N,N-dimethylformanid, and the obtained coloured product was subjected to spectrophotometric analysis at the Spectrophotometer Unicam SP 8000 B. Homogeneity of the coloured product eluted from the sections as well as its identity with the coloured product obtained during the reaction with a preparation of crystalline acid phosphatase was found. Repeatability of the obtained activity for the inbred animals was shown. The obtained results were subjected to statistical analysis. The method of quantitative estimation of AcP activity may be useful in histoenzymatic works.


Anterior instability in the ankle joint following acute lateral sprain. The relation between anterior instability in the ankle joint and rupture of the anterior talofibular ligament was investigated in patients with acute ankle sprains. Various techniques were used to provoke anterior displacement of the talus. The actual condition of the anterior talofibular ligament was assessed at operation. The appropriate radiographic method was defined, and its valve in diagnosing an acute rupture of the anterior talofibular ligament was assessed.


Oral immunization of monkeys with polyvalent dysentery vaccine. Macaca mulatta monkeys were immunized orally with polyvalent Boivin extract of Shigella flexneri 2a, 3a, 4a, 4b, 6 and Shigella sonnei. The total immumizing dose for each component was equivalent to 1.2 X 10(12) cells. After challenge with 7.5 X 10(10) cells of a virulent S. flexneri 2a strain, out of 20 immunized animals 2 developed dysentery and 4 showed mild dyspepsia; all 6 control animals became ill with dysentery. Vaccination failed to influence the incidence, duration or the intermittent character of shigella excretion. Protective antibodies appeared in high titre in the serum of immunized animals.


[Early post-traumatic epilepsy in childhood: significance and short term prognosis (author's transl)]. In the last five years, 244 children with head trauma were observed. An early post-traumatic epilepsy was present in 11% of the patients. This complication was more frequent in children less than six years of age or presenting a previous neurological history. Early posttraumatic epilepsy was rarely associated with brain concussion and frequently with cerebral contusion. An intracranial haematoma was not encountered in the absence of the classical signs of expanding space occupying lesion.


Evaluation of some standard arthritogenic adjuvants ('modified perrigens') in male rats. Four commercially available arthritogenic adjuvants ('modified Perrigens') were compared with a Mycobacterium butyricum-mineral oil adjuvant for their ability to induce arthritis in male Holtzman rats. The induced arthritides were also compared with respect to their response to treatment with phenylbutazone and cyclophosphamide. Trivial differences were noted among the various adjuvants in their capability to induce the disease, the severity of the disease, or the response of the disease to therapeutic (phenylbutazone) or prophylactic (cyclophosphamide) administration of drugs. It was concluded that any one of the adjuvants was probably suitable for inducing an arthritis in rats for the testing of drugs and that perhaps other variables in the assay are more important in explaining inter-laboratory variation.


Neonatal resuscitation.

Neonatal resuscitation. A variety of common situations result in asphyxia of the newborn. The infant may be born in secondary or terminal asphyxia. The infant at greatest risk of neurologic sequelae is the low birth weight infant with a low five-minute Apgar score. Personnel must be trained and the delivery room must be properly equipped for successful resuscitation. For example, a radiant warmer is essential. Meconiumstained infants require special care. Meconium must be removed from the airway. The list of postasphyxial complications is formidable.