[Changes in serum proteins,-iron and -copper in swimmers before and after altitude training (author's transl)]. Fifteen  male swimmers (mean age 19.3 +/- 2.1 years) were subjected to a standard 120 min swimming exercise test: a) before, and b) after 5 weeks of intensive training at middle altitude (2000 m). At rest, serum levels of alpha2-macroglobulin, transferrin and copper were elevated in swimmers as compared to untrained subjects. After the altitude training program, significant increases of the parameters of iron and copper metabolism, as well as of alpha2HS-glycoprotein and beta1A-globulin were observed. After the first exercise test (a), a significant rise in serum alpha1-acid glycoprotein, alpha1-antitrypsin, hemopexin, alpha2-macroglobulin, ceruloplasmin, transferrin, iron, copper and alpha2-HS-glycoprotein was noted. The same 120 min-exercise test after the altitude training (b) led to only small changes, especially as concerns the parameters of iron metabolism. The characteristic immediate and long-lasting changes in serum proteins and heavy metals in swimmers and the effects of training in middle altitude on the answer of the organism to swimming exercise with respect to the mentioned biochemical parameters are discussed.


[Adaption of subjects in field studies of informatory working conditions (author's transl)]. Processes of adaption in measurements of performance - cycle-times, variance of cycle-times, informatory component of time and errors - and of physiological strain - electromyograms of musculus extensor digitorum and musculus rhomboideus, horizontal and vertical electrooculogram, heart rate and heart rate variability - are presented and described in type and frequency. Simultaneous reactions and successive reactions of measured variables in dependance of shift-time and of days are described. They are classified according to the causes "exercise" and "emotional habituation" and discussed in a model "experimenter - experimental situation".


Physical performance capacity of children in Norway. Part IV. The rate of growth in maximal aerobic power and the influence of improved physical education of children in a rural community - population parameters in a rural community. During a period of 4 years the annual increase of the physical performance of 31 boys and 34 girls was examined in a longitudinal study. In spite of the expected mean increase of the physical performance unsystematic annual variations of the increase of the maximal oxygen uptake related to body weight were observed. These variations can only be explained by the variations of the daily physical activity. The fact that in the longitudinal study a clear better performance over the years was observed than in a cross sectional study which was performed in the first year of the longitudinal study confirms this tendency. This can partly be explained by the improvement of the possibilities for physical activities in the community since the begin of the longitudinal study.


Measurement of gas free body volume by a diving device. A device is presented for determination of gas free body volume, by which total body volume as well as lung volume together with intestinal gas can be measured. The measurement is performed under water. The subject to be measured keeps his head in an airfilled cylinder which allows free breathing during the measurement procedure under water. The subject sits on a seat which is connected with a vertical "probe" that is submerged in a water basin. This "body density probe" carries several measuring rods of different diameter on its upper end, which lead to an increase of buoyancy when sinking deeper into the water after additional weights have been put on the device. These rods lead to new equilibrium states which are also dependent on the compressable gas volume attached to the probe. Three equilibrium states with different added weights give a physical definition of gas free body volume, which  can be calculated from a number of accurately measurable single items.


Changes of free amino acids in plasma of healthy subjects induced by physical exercise. In eight healthy men a 20-min load of 1.5 W/kg body weight on a bicycle ergometer led to a significant increase of alanine and decline of leucine. Exhausting exercise caused in the same subjects a highly significant increase of alanine and decline of isoleucine, threonine, ornithine, leucine, serine, glycine, and asparasine and glutamine. The methionine and citrulline level declines also significantly. The total amino acids practically did not change. Physical exercise led furthermore to a marked increase of serum ammonia and uric acid. Urea nitrogen changed only little and on average had rather a declining tendency. The rise of alanine suggests the existence of a glucose-alanine cycle, the drop of ornithine and citrulline is most probably associated with the inhibition of ureogenesis in the liver. The reduction of leucine and isoleucine is probably the result of the entry of these amino acids into muscle and their deamination.


Pulmonary O2 diffusing capacity at exercise by a modified rebreathing method. The rebreathing technique for the measurement of the pulmonary O2 diffusing capacity, DO2, previously developed for resting conditions [Cerretelli et al., J. appl. Physiol. 37, 526-532 (1974)] has been modified for application to exercise and simplified to one rebreathing maneuver only. The changes consist: 1) in administering in the course of a normoxic exercise a priming breath of an O2 free mixture just before the onset of rebreathing in order to achieve rapidly the appropriate starting PO2  values on the linear part of the O2 dissociation curve as required by the method; 2) in calculating mixed venous blood O2 tension by extrapolation of the alveolar to mixed venous blood PO2 equilibration curve, instead of determining it separately. While the mean DO2 value of 21 measurements on 5 subjects at rest was 30 ml-min-1 - Torr-1 +/- 3 (S.E.), in 2 subjects exercising on a bicycle ergometer, DO2 was found to increase from a resting value of about 32 ml- min-1 - Torr-1 to 107 ml - min-1 - Torr-1 for an eightfold increase of O2 uptake. The validity and the applicability of the method are critically discussed.


Hamster brown-adipose-tissue mitochondria. Purine nucleotide control of the ion conductance of the inner membrane, the nature of the nucleotide binding site. The inner membrane of hamster brown adipose tissue mitochondria possesses a mechanism for the conductance of protons (or hydroxyl ions) and halide anions which may be specifically inhibited by exogenous purine nucleoside di- or triphosphates. The mechanism of the nucleotide interaction is examined. The added nucleotides can inhibit the ion conductances without equilibrating with the matrix pools of purine nucleotides. ADP translocation is completely sensitive to atractylate, and no mechanism for GDP translocation could be detected. The nucleotides act on the conductance mechanism without covalent modification. A purine nucleotide binding site is described which is distinct from the adenine nucleotide translocase, does not bind atractylate, has a capacity of 0.7 nmol - mg-1, and affinities, specificities and a pH dependency closely corresponding to the conditions required for the inhibition of the ion conductances. The binding site is not apparent in rat liver mitochondria. A causal relationship is suggested between the occupation of this site by added purine nucleotides, and the inhibition of the ion conductance pathway. The role of the pathway in the physiological control of non-shivering thermogenesis by the tissue is discussed.


Evidence that DNA polymerase-alpha of calf thymus contains a subunit of molecular weight 155000. Small samples of the 8-S species of enzymes (A1 and A2) occurring in the DNA polymerase-alpha fraction of calf thymus, have been extensively purified using non-denaturing (normal) polyacrylamide gel electrophoresis. When peak fractions of activity on normal gels were subjected to dodecylsulphate-polyacrylamide gel electrophoresis, a polypeptide at 155000 correlated with polymerase activity. Samples of the 7.3-S (C) enzyme prepared from A2 by treatment with 2.4 M urea or isolated directly without exposure to urea, also showed the presence of a 155000-Mr polypeptide. It is concluded that the 7.3-S (C) enzyme, of previously estimated molecular weight 155000-170000, is a single polypeptide and that the 8-S enzymes A1 and A2 contain an additional subunit of 50000-70000 molecular weight.


N-acetyl-9-O-L-lactylneuraminic acid, a new acylneuraminic acid from bovine submandibular gland. The acylneuraminic acid fraction, obtained on mild acid hydrolysis of glycoproteins from bovine submandibular glands, contains approximately 2% N-acety-9-O-L-lactylneuraminic acid. The compound has been isolated and purified by ion-exchange and cellulose column chromatography. The structure has been elucidated using thin-layer chromatography, colorimetry, gas-liquid chromatography/mass spectrometry, periodate oxidation and specific lactate dehydrogenases. An evaluation of the different analytical methods is given.


The binding of Met-tRNAf to isolated 40-S ribosomal subunits and the formation of Met-tRNAf - 80-S-ribosome initiation complexes. Different forms of 40-S ribosomal subunit, distinguishable by their buoyant densities on CsCl equilibrium density gradients, are formed when derived 40-S ribosomal subunits are incubated with partially purified reticulocyte ribosomal wash proteins. One of these subunits, the 1.37-g-cm-3 form is not present in the cell but the other two forms, the 1.40-g-cm-3 and 1.40-g-cm-3 subunits, are present in cell extracts. 35S label is bound to 1.37-g-cm-3 and 1.40-g-cm-s subunits when [35S]Met-tRANf, GTP and poly(A,U,G) are included in the incubations. The 35S-labelled 40-S subunits recovered, and the amount of 35S label bound to them, are changed if the [35S]Met-tRNAf-40-S-subunit-poly(A,U,G) complexes are first purified on sucrose gradients before analysing them on CsCl. The 1.37-g-cm-3 particle is no longer seen and the total quantity of 35S label on the 40-S subunits is 90% lower after sucrose gradient purification. Between 30% and 40% of the 40-S subunits bind [35S]Met-tRNAf when 1 mM GTP, an excess of ribosomal wash proteins and [35S]Met-tRNAf over derived 40-S subunits, and poly(A,U,G) or AUG is included in the incubations. The omission of poly(A,U,G) or AUG from the incubations substantially lowers the amount of subunit-bound 35S label ultimately recovered. With these incubations less than 10% of the 40-S subunits have bound [35S]Met-tRNAf. [35S]Met-tRNAf binding is affected by the nature of the RNA added. The addition of poly(U), rRNA and native 9-S golbin mRNA is without effect, whereas denatured globin mRNA is stimulatory. Maximum binding is obtained however with AUG. Poly(A,U,G) is less stimulatory than AUG but more stimulatory than denatured mRNA, suggesting that the number as well the accessibility of the AUG initiations condons determines the amount of 35S label bound. Similar results are obtained for the ribosomal-wash-dependent binding of [35S]Met-tRNAf to 80-S ribosomes. Contrary to the binding results, the ability of mRNA to stimulate protein synthesis is dependent on the integrity of the mRNA. Thus, native 9-S globin mRNA but not poly(A,U,G) stimulatex protein synthesis in the wheat germ system. HCHO-treated globin mRNA, although stimulatory, is 45% less effective than  native mRNA. The addition of AUG, derived 60-S subunits and extra ribosomal wash is required for the formation of [35S]Met-tRNAf-80-S-ribosome complexes from sucrose-gradient-purified [35S]Met-tRNAf-40-S-subunit complexes. The 80-S ribosome complexes are able to form peptide bonds. Thus, if puromycin is added to the full incubations at zero time, no 35S label is present on the 80-S ribosome. 35S label is released as methionyl-puromycin. If the [35S]Met-tRNAf-40-S-subunit complexes are assembled with poly(A,U,G) or AUG in the incubations and then purified, only derived 60-S subunits are required to form [35S]Met-tRNAf-80-S-ribosome complexes. 35S label is not released from them when puromycin is added to the incubations unless extra ribosomal wash is also added.


Binding of secretory component to dimers of immunoglobulin A in vitro. Mechanism of the covalent bond formation. A complex between secretory component and an immunoglobulin A (IgA) myeloma dimer has been studied in vitro as a model to elucidate the mechanism of the formation of disulfide bonds during assembly in vivo of secretory immunoglobin A. A small amount of free thiol groups, totally about 0.4 groups per mole of protein, were shown to be present on both the heavy and light chains of the IgA dimer, but not on its J-chain, while no such groups could be demonstrated on free secretory component. The SH-groups on IgA most likely exist as a result of incomplete oxidation of some intra-or interchain disulfide bonds of the molecule, analogous to what has been suggested for IgG. Several types of evidence indicated that the disulfide bonds between secretory component and IgA are formed after the noncovalent association of the two proteins by a sulfhydryl group-disulfide bond exchange reaction, in which the small amount of free sulfhydryl groups on the IgA dimer initiate the reaction by reducing a reactive disulfide bond on secretory component. This exchange reaction, which thus proceeds by the mechanism of so-called disulfide interchange reactions, requires certain conformational features of one or both of the proteins and leads to the formation of presumably two new interchain disulfide bonds between secretory component and IgA. The reaction does not progress to completion, however, but ends in an equilibrium so that a small proportion of the secretory component molecules always are unattached by disulfide bonds.


Organization of vitellogenin polysomes, size of the mRNA and polyadenylate fragment. A heavy polysome fraction containing vitellogenin mRNA was isolated from the liver of oestradiol-treated chicks. As determined by urea-polyacrylamide gel electrophoresis, the molecular weight of vitellogenin mRNA is about 2.5 x 10(6). The mRNA contains a polyadenylate segment of about 220 nucleotides at the 3' end. The remaining 7000 nucleotides are sufficient to code for a polypeptide of Mr about 270000. Combining 'run off' experiments of heavy polysomes in vitro together with radioimmunoprecipitation and polyacrylamide gel electrophoresis of the translation product, we concluded that vitellogenin mRNA is probably monocistronic and the 2.5 x 10(6)-Mr mRNA codes for two polypeptides, Mr 30000 and 240000. The largest polypeptide is, in our cell-free system and liver homogenate, readily cleaved into smaller peptides.


On the mechanism of amylose branching by potato Q-enzyme. 1. When potato Q-enzyme converts amylose into an amylopectin-like molecule, the action is by a random, endo-type transglycosylation of the substrate chains. 2. Inter-chain transfer takes place during the formation of the amylopectin branch linkage. This is seen in experiments in which radioactive label was transferred between substrates of disparate molecular weight. Intra-chain transfer, leading to the formation of a branch linkage, is not excluded by these experiments. 3. The minimum length of amylose chain that can act as an acceptor in the transglycosylation reaction, under the experimental conditions described, is greater than 40 glucose units. 4. The requirement of Q-enzyme for substrate chains at least 40 glucose units in length is interpreted as meaning that a stabilized secondary and tertiary structure must be established in the substrate before it can be utilized by Q-enzyme, and that the forces that provide such conformation are sufficiently strong only when the chains are longer than the minimum. Inter-chain transfer is seen as taking place by one of two mechanisms. The first involved the reaction of the enzyme with a chain that has a stabilized (helical?) conformation. An enzyme-donor chain intermediate is formed, that then reacts with an acceptor chain to complete the transglycosylation. The second mechanism envisages the substrate for the enzyme as being a complex formed between two chains (a double helix?). The enzyme encounters the complex and carries out an inter-chain transglycosylation reactions.


Molecular-weight determination of animal-cell RNA by electrophoresis in formamide under fully denaturing conditions on exponential polyacrylamide gels. A method for electrophoretic analysis of RNA under fully denaturing conditions on exponential gradient polyacrylamide gels is described. Full denaturation, and strand separation of DNA - RNA hybrids and double-stranded RNA is obtained in dry formamide only if electrophoresis is carried out at 45 degrees and 55 degrees C, respectively. In such conditions, the effects of secondary structure of RNA, important in aqueous medium, are suppressed and a linear correlation is obtained between the logarithm of the molecular weight of an RNA and its final position in the gel over the entire molecular weight range of 10(4) - 10(7). Based on absolute molecular weight standards, obtained from sequenced rRNA of Escherichia coli and tRNA and extrapolating to higher molecular weights the size of animal cell was reexamined.  Precursor tRNA from HeLa cells migrates according to a molecular weight of 4.1 x 10(6). Nascent precursor mRNA has molecular weights of up to 5 x 10(6) in the case of duck erythroblasts and of up to 10(7) in HeLa cells. This seems to represent the largest size of non-viral animal-cell RNA molecules.


Transcription of specific genes in isolated nuclei from HeLa cells in vitro. Isolated HeLa cell nuclei were employed to catalyze the synthesis of RNA in vitro. In the presence of low concentrations of alpha-amanitin (1 mug/ml), used to suppress the formation heterogeneous nRNA, these nuclei synthesize RNA very efficiently for extended periods of time (at least 60 min) at an elongation rate of about seven nucleotides per second. The product, analyzed on sucrose density gradients and polyacrylamide gels was found to exist of two predominant size classes. Synthesis of the 45-S ribosomal precursor was completely resistant even to high concentrations of alpha-amanitin (150 mug/ml) and hence was catalyzed by enzyme A (or I). A limited degree of processing of the 45-S precursor occurred in vitro. In addition, a second RNA class of low molecular weight (4-8 S) was synthesized by HeLa cell nuclei in the presence of 1 mug/ml alpha-amanitin in vitro. Analysis on 8% polyacrylamide gels resolved the RNA into four distinct components. Their synthesis was resistant to low (1 mug/ml) but clearly sensitive to high (150 mug/ml) concentrations of alpha-amanitin. Consequently the synthesis of all these small-molecular-weight RNA species is catalyzed by RNA polymerase C (or III). For the assessment of the initiation frequency of the individual classes of RNA, a new technique was developed independent of labelling the 5' end of the RNA molecule with the gamma-phosphate of the initiating nucleotide. It employs the double labelling of an RNA molecule with two different isotopes added sequentially at different stages of completion of the chain. From the incorporation ratio of the two isotopes into a particular class of RNA, conclusions can be drawn concerning their initiation frequency. The results obtained have shown a high reinitiation frequency for the small-molecular-weight RNA species at all stages of the incubation reaction. In contrast, reinitiation of the 45-S precursor RNA occurs only to a limited extent in isolated HeLa cell nuclei in vitro.


Comparison of cytoplasmic and nuclear poly(A)-containing RNA sequences in Xenopus liver cells. Poly(A)-containing RNAs from cytoplasm and nuclei of adult Xenopus liver cells are compared. After denaturation of the RNA by dimethysulfoxide the average molecule of nuclear poly(A)-containing RNA has a sedimentation value of 28 S whereas the cytoplasmic poly(A)-containing RNA sediments slightly ahead of 18 S. To compare the complexity of cytoplasmic and nuclear poly(A)-containing RNA, complementary DNA (cDNA) transcribed on either cytoplasmic or nuclear RNA is hybridized to the RNA used as a template. The hybridization kinetics suggest a higher complexity of the nuclear RNA compared to the cytoplasmic fraction. Direct evidence of a higher complexity of nuclear poly(A)-containing RNA is shown by the fact that 30% of the nuclear cDNA fails to hybridize with cytoplasmic poly(A)-containing RNA. An attempt to isolate a specific probe for this nucleus-restricted poly(A)-containing RNA reveals that more than 10(4) different nuclear RNA sequences adjacent to the poly(A) do not get into the cytoplasm. We conclude that a poly(A) on a nuclear RNA does not ensure the transport of the adjacent sequence to the cytoplasm.


EEG spectral analysis in children with febrile convulsions. The abnormal theta-rhythm of the EEG can be identified by use of spectral analysis. The rhythms appear as peaks in the power spectrum and can be considered as given, if the intensity of this peak is significantly higher than the average intensity and if a left-right coherence is present. Abnormal theta-rhythms in the parietal region are significantly more frequent in children with a histroy of febrile convulsions than in controls. This difference becomes especially obvious in the records with open eyes. According to previous investigations, the abnormal theta-rhythm is correlated with a genetically determined susceptibility to convulsions.


Visual evoked responses and their dispersion pattern in frontal lobe tumours. In patients with frontal lobe tumours the averaged visual evoked responses (AVER) and their dispersion pattern (DP) in visual areas were investigated before and at different periods after operation. Important changes in AVER (in amplitude and latency) were found in the patients with tumours on the midline or in one of the frontal lobes. The DP was abnormal in all the cases. There was no relation to visual acuity, tumour location and existance of intracranial hypertension. After operation, despite the clinical improvement, the alterations of AVERs or DPs were very marked and in some cases became even more important than before. The role of the frontal lobe in the organization of the responses to peripheral stimuli in the visual areas is discussed.


Encephalopathy subsequent to accidental poisoning with chlorpromazine. A cerebral biopsy performed in an infant 9 months after accidental poisoning with chlorpromazine was studied. Light microscopy disclosed necrosing encephalopathy, while electron microscopy showed neuronal, glial, myelinic and vascular lesions. The findings in the present study suggest that the various neurologic syndromes appearing in cases of prolonged treatment with neuroleptic drugs and persisting after cessation of therapy would be due to consequent occurrence, in specific areas, of some irreversible cerebral lesions.


Occult normal pressure hydrocephalus with parkinsonian symptomatology. The authors describe a case where a parkinsonian symptomatology is associated with pneumoencephalographic and RISA-cisternographic findings typical of an occult normal pressure hydrocephalus. They discuss their personal contribution in the light of what has been already reported in the literature on the same subject. They conclude that a CSF dynamics disturbance among the possible physiopathogenetic mechanisms of an extrapyramidal syndrome in young subjects should be considered. On the other hand, they also emphasize the possibility that the occult normal pressure hydrocephalus may have syndromical expression which are different from the typical one initially described.


Measurement of jugular venous blood gases for prediction of brain ischaemia following carotid ligation. A comparison with direct measurements of cerebral blood flow. Measurements of various indices derived from arterial and jugular venous blood gas and pH values during temporary carotid clamping have been compared with measurements of cerebral blood flow and internal carotid artery pressure in 15 patients referred for carotid ligation. Cerebral venous blood gas measurements did not provide a reliable index of cerebral ischaemia.


A reappraisal of the significance of thymic germinal centers in myasthenia gravis. The morphology of thymuses removed from 16 cases of myasthenia gravis was studied in an attempt to correlate clinical response following thymectomy with the frequency of thymic germinal centers. In these patients, the presence of germinal centers in the thymus did not appear to influence response to thymectomy.


Results of electromyographical and electroneurographical investigations concerning syringomyelia. 16 patients suffering from syringomyelia were checked for additional peripheral nerve lesions. On voluntary effort, often in conformity with the decrease of muscle strength, a moderate rarefication of the discharge patterns was apparent. Fasciculation potentials were common. Motor conduction velocities of the median and ulnar nerve were in the normal range in cases without additional peripheral nervous lesion at the elbow or the carpal. Depending on the severity of the peripheral nervous lesion, we found the duration of the muscle action potentials increased.


Liver function and gastric acid secretion in parkinsonian patients under prolonged treatment with L-dopa and a peripheral decarboxylase inhibitor. Twelve patients with long-standing Parkinson's disease, treated successfully with a combination of l-dopa and an inhibitor of aromatic l-amino acid decarboxylase (Ro 4-4602), in the ratio 4:1, were screened for damage to various organ systems, in particular liver and skeleton. Among other tests, liver biopsies were obtained before and after 6 months of treatment. One patient discontinued therapy becuase of an accentuation of pre-existent liver damage, another because of psychomental manifestations. The remaining ten patients were followed for 8-15 months and longer. The liver biopsies remained practically unaltered. Elevation of alkaline phosphatase was found in 10 out of 12 subjects. In five patients this rise fluctuated around the upper limit of normal. In two patients, who discontinued the treatment, the raised alkaline phosphatase values soon returned to normal. Analysis of isozymes proved this phosphatase to be of liver origin. All other liver function tests remained unchanged, except for an increased retention of bromsulphalein in two patients. In the one patient with the initially damaged liver, all tests became normal soon after discontinuation of therapy. No changes could be found in gastric acid secretion. All other parameters studied remained within normal limits, including urinary excretion of calcium and phosphate.


The effect of spironolactone on transport of Na+, K+ and H+. A microperfusion study in rat main submaxillary duct. The epithelium of the main excretory duct of the rat submaxillary gland was used as a target tissue for studies on the effect of a spironolactone on electrolyte transport. The spironolactone decreased net Na+ reabsorption by 27% and net K+ secretion by 23%. HCO-3 was found to be about 2-fold accumulated in the duct lumen, which was considered to result from decreased H+ion secretion. The results can be reconciled with an action of spironolactone on 1) the peritubular Na+-K+-exchange mechanism and 2) the functional coupling of Na+ entry from lumen to cell with K+ and H+ transfer from cell to lumen.


Phenazone metabolism in patients with liver disease. Phenazone metabolism was studied in 14 patients with liver disease and six normal volunteers. The plasma and renal clearance of phenazone and the 4-hydrozyphenazone excretion in urine was significantly decreased in the patients with liver disease. The urinary excretion of 4-hydroxyphenazone was significantly correlated to the plasma clearance of phenazone (r= + 0.95, P less than 0.001), to quantitative liver function as measured by the galactose elimination capacity (r= + 0.95, P less than 0.001), and to the prothrombin values (r= + 0.82, P less than 0.001). The determination of the 4-hydroxyphenazone excretion in urine may be used as an easy and non-invasive test of quantitative liver function.


Diabetes mellitus in gonadal dysgenesis: studies of insulin and growth hormone secretion. On the basis of results obtained from an oral glucose tolerance test, (OGTT), twenty patients with gonadal dysgenesis were classified as normal (N = 8) and diabetic (N = 12). The two groups of patients were further tested by a rapid intravenous glucose injection, a tolbutamide test, an insulin sensitivity test and an oral amino acid load. Fasting levels of plasma growth hormone (GH) were normal in all subjects but one. Approximately 1/3 of the GH responses during testing periods were abnormal, being either absent during hypoglycaemia or following amino acid ingestion, or paradoxically increased during hyperglycaemia. No correlation was found between the degree of carbohydrate intolerance and the levels of plasma GH. There was no gross alteration of tissue sensitivity to exogenous insulin. The beta-cell response to tolbutamide, amino acid and intravenous glucose were comparable in patients with  a normal or a diabetic OGTT. In both groups, the rates of decrease of blood glucose following tolbutamide or intravenous glucose were also similar and within the normal range. During OGTT, the diabetic group had a delayed insulin release and a low insulinogenic index. It is concluded that in gonadal dysgenesis the intolerance to an oral carbohydrate load is frequently associated with, but unrelated to, anomalies of the GH secretion. In diabetic subjects, the process of insulin secretion loses its normal sensitivity to the oral glucose stimulus while remaining unaltered and similiar to that of non-diabetic subjects in response to tolbutamide, amino acid and intravenous glucose.


Bile salt glucuronides: identification and quantitative analysis in the urine of patients with cholestasis. Glucuronides of lithocholate, chenodeoxycholate and cholate were synthesized enzymatically and characterized by thin layer chromatography, column chromatography and specific enzymatic hydrolysis. Bile salt glucuronides were quantitatively analysed in thr urine of patients with intra- and extra- hepatic cholestasis and were found to be present in 19 out of 20 patients studied. Our patients with intrahepatic cholestasis excreted 8.9 mg non-sulphated and non-glucoronidated bile salts, 18.2 mg sulphated bile salts and 7.2 mg glucuronidated bile salts. The patients with extrahepatic cholestasis excreted 14.7 mg non-sulphated and non-glucuronidated bile salts, 20.7 mg sulphated bile salts and 4.7 mg glucuronidated bile salts. These findings indicate that glucuronidation of bile salts occurs in man and represents a metabolic pathway in patients with cholestasis.


Effects of myocardial revascularization following acute coronary occlusion in pigs. In a comparative study in pigs the extent of myocardial infarction has been estimated following a temporary three hour coronary occlusion and following a permanent coronary ligation. For evaluation of the cellular injury the infarct size has been determined by a histochemical staining procedure and correlated with serum enzyme studies (creatine phosphokinase, alpha-hydroxybutyric dehydrogenase) in the surviving animal. No significant difference could be detected between the two experimental groups and the extent of cellular damage was similar. A strict linear correlation was found between the serum enzyme activity plotted logarithmically and the morphological infarct size. Likewise the incidence of ventricular fibrillation depended on the extent of cellular injury. Myocardial revascularization does not appear to benefit a pig heart subjected to an acute coronary occlusion lasting three hours or more. Revascularization may even be harmful by creating a haemorrhagic infarct, as found in all the animals submitted to a transient coronary occlusion.


Sodium balance and renal tubular sensitivity to aldosterone during total fast and carbohydrate refeeding in the obese. In man the first days of fasting are characterized by enhanced natriuresis despite an increase in aldosterone secretion. Therefore the possibility of a decreased renal tubular sensitivity to this hormone was considered. The response to aldosterone infused before a fast and again on day 4 of fasting was evaluated in 12 starving obese women in terms of urinary sodium, chloride and potassium excretion. The data were compared to those obtained from 20 untreated starving obese women. In addition, salivary flow and sodium output were measured before and after aldosterone infusion in 4 out of the 12 patients treated. The involvement of aldosterone in the mechanism of fasting natriuresis and glucose-induced sodium retention was evaluated by means of spironolactone treatment (Aldactone A; 300 mg/day p.o.) on days 6 to 8 of the fast, with an oral glucose load (100 g) on day 7. Aldosterone infused on day 4 of the fast caused on average only 40% of the antinatriuretic effect it achieved before the fast. On the other hand even before aldosterone infusion, salivary sodium output was markedly reduced during the fast to levels comparable to those observed after aldosterone treatment in the pre-fast period. Furthermore, spironolactone administration on day 6 of the fast was associated with a prompt and marked increase in natriuresis. These 3 sets of facts indicate a definite biological activity of aldosterone during the initial phase of fasting with factor(s) interfering at the renal level with the normal expression of the hormonal action on sodium balance. There was still a distinct antinatiuretic effect of glucose in the presence of spironolactone, but less pronounced than when glucose was administered alone. The well-documented hyperaldosteronism of a total fast may represent a compensatory mechanism to decrease sodium loss at the end of a week-long fast. In addition a marked sodium-retaining effect of glucose can be demonstrated after aldosterone action is blocked by spironolactone. This provides another indication that glucose stimulates sodium retention through mechanism(s) which do not involve aldosterone.


Effects of fructose and glucose on ethanol-induced metabolic changes and on the intensity of alcohol intoxication and hangover. The effects of fructose and glucose on the metabolic changes induced by ethanol and on the intensity of alcohol intoxication and hangover were studied in 109 healthy male volunteers. After 10 hours of fasting, the subjects were given 1.75 g of ethanol per kg body wt during 3 hours under controlled laboratory conditions. Fructose or glucose were adminstered either simultaneously with ethanol or 12 hours later during the hangover period. The intensity of alcohol intoxication and hangover were estimated 10 times during the experimental period of 20 hours using subjective and objective rating scales. Sequential determinations of blood ethanol, acetaldehyde, glucose, lactate, free fatty acids, triglycerides, ketone bodies and capillary blood acid-base balance were also made during the experiment. Under these experimental conditions neither fructose nor glucose had any significant effect on the intensity of alcohol intoxication and hangover. The sugars also had no significant effect on the rate of ethanol elimination or on the blood acetaldehyde concentration during the course of the experiment. Blood glucose concentration was decreased and blood lactate, free fatty acid and ketone body concentrations were increased during the hangover period in the subjects who had been given only ethanol. These subjects also had a marked metabolic acidosis during hangover. Glucose and fructose significantly inhibited the metabolic alterations induced by ethanol. In this respect fructose was more effective than glucose. The results indicate that both fructose and glucose effectively inhibit the metabolic disturbances induced by ethanol but they do not affect the symptoms or signs of alcohol intoxication and hangover. The results support the view that hangover is not directly related to the metabolic effects of ethanol or to its metabolic products.


The importance of 5-hydroxytryptamine for the induction of harmine tremor and its antagonism by dopaminergic agonists assessed by lesions of the midbrain raphe nuclei. The brain lesion technique was used to destroy the ascending 5-hydroxytryptamine (5-HT) system at its cell bodies in the dorsal and medial raphe nuclei in order to assess the importance of 5-HT for the induction of harmine tremor and its antagonism by the dopaminergic agonists, L-DOPA, apomorphine and d-amphetamine. Lesions of the medial or dorsal raphe nucleus reduced the intensity of harmine tremor. The remaining tremor was generally resistant to further reduction by the dopaminergic agonists. 5-hydroxytryptophan was shown to enhance tremor: this effect was reduced both by the raphe lesions and by treatment with L-DOPA. The data are discussed in terms of the possible relationship between 5-HT and dopamine.


Photoaffinity labeling of the beta-adrenergic receptors and receptor reserve for isoprenaline. The beta-adrenergic receptors in the taenia isolated from the guinea pig caecum were irreversibly inactivated by photoaffinity labeling with 1-isoprenaline and 2-(2-hydroxy-3-isopropylaminopropoxy)iodobenzene. The photoinactivation was eliminated in the presence of protectors of the receptors. Photoinactivation caused a considerable parallel shift in the concentration-action curve of 1-isoprenaline. The results possibly point to a certain receptor reserve for 1-isoprenaline.


Modification of the L-DOPA reversal of reserpine akinesia by inhibitors of dopamine-beta-hydroxylase. The effect of the dopamine-beta-hydroxylase inhibitors (DBHI) FLA-63 and U10,157 on the reversal of reserpine akinesia by L-DOPA in mice was investigated both behaviourally and by measurement of the cerebral amines dopamine and noradrenaline. Pretreatment of reserpinised animals with intraperitoneal, but not oral, FLA-63 produced hypermotility in the first hour after L-DOPA administration, compared to animals receiving L-DOPA alone. This enhanced activity was associated with an increase in dopamine, but no significant change in the noradrenaline content of whole brain. Pretreatment with both oral and intraperitoneal FLA-63 caused dose-dependent suppression of locomotor activity in the second and third hours after L-DOPA. This suppression was associated with a significant decrease in brain noradrenaline in the presence of a significant elevation in brain dopamine. Pretreatment of animals with U10,157 produced similar but less marked behavioural responses. The results do not appear to be due to stressful effects of DBHI's, causing release of corticosteroids; neither corticosterone nor beta-methasone had any significant effect on L-DOPA-induced locomotor activity in reserpinised animals, although they did increase spontaneous motor activity in normal animals. The data presented support the concept that both noradrenaline and dopamine are responsible for the gross motor activity induced by L-DOPA in the reserpinised mouse.


Regional differences in the response to nicotine in isolated canine arteries. Helically cut strips of canine cerebral, coronary, femoral, mesenteric and renal arteries were contracted with prostaglandin F2alpha. In response to 10(-4)M nicotine, cerebral arterial strips showed a transient relaxation, which was abolished by hexamethonium, cocaine and propranolol but was not significantly influenced by sotalol and tetrodotoxin. In coronary arteries, biphasic response, relaxation followed by contraction, to 8 X 10(-4)M nicotine and contractile response to 10(-4)M nicotine were not influenced by hexamethonium, cocaine and propranolol. Initial contraction and relaxation of femoral arteries induced by nicotine were abolished by hexamethonium and cocaine. Phentolamine (2 X 10(-7)M) attenuated the contraction but not the relaxation, while sotalol (10(-5)M) reduced the relaxation without alterations in the contractile response. In mesenteric and renal arteries, the contractile response to nicotine was abolished by hexamethonium, cocaine, bretylium and phentolamine, but was attenuated only partially by tetrodotoxin. It may be concluded that nicotine exerts a relaxation in cerebral arteries by a mechanism different from the adrenergic one, and a non-specific relaxation and contraction in coronary arteries. It appears that initial contractions of femoral, mesenteric and renal arteries and also relaxation of femoral arteries in response to nicotine are associated with the release of noradrenaline; however, the mechanism of the amine release is different from that with transmural stimulation, in which the nerve action potential is involved.


Antagonism of the hyperactivity induced by dopamine applied intracerebrally to the nucleus accumbens septi by typical neuroleptics and by clozapine, sulpiride and thioridazine. Dopamine administered intracerebrally to the nucleus accumbens septi was shown to induce a dose-dependent hyperactivity following pretreatment with nialamide. This effect was optimum following the injection of 50 mug dopamine. The hyperactivity induced by this dose of dopamine was inhibited by the i.p. injection of both the typical neuroleptic agents, haloperidol, fluphenazine, pimozide and clothiapine (0.05--0.5 mg/kg i.p.), and the atypical neuroleptics clozapine, sulpiride and thioridazine (0.5--20 mg/kg i.p.) although, generally, the doses required ot the latter were in the order of 20--100 times those of the typical agents to produce an equivalent effect. In contrast, cataleptic doses of metoclopramide (10--30 mg/kg i.p.) failed to reduce the dopamine-induced hyperactivity: aceperone and propranolol were similarly ineffective. However, inhibition of hyperactivity was recorded following the peripheral administration of the antimanic drug, IB503. It is suggested that the ability of a drug to antagonise the hyperactivity induced by the injection of dopamine into the nucleus accumbens septi may be of value in the detection of antipsychotic activity.


Pharmacologic analysis of papaverine-induced positive chronotropic and inotropic effects. Effects of papaverine on sinus rate and atrial contractility were investigated using the isolated atrium preparation of the dog perfused with heparinized arterial blood led from a support dog. When papaverine was injected into the cannulated sinus node artery, positive chronotropic and inotropic responses were dose-relatedly produced from about 3 mug. At a dose level above 100 mug, papaverine induced initially slightly negative chronotropic and inotropic effects followed by marked positive ones. Papaverine-induced positive chronotropic and inotropic effects (P-PCIE) were not influenced by treatment with tetrodotoxin which blocked the action of nicotine. P-PCIE were slightly suppressed by an adrenergic beta-blocking agent, alprenolol, which blocked the action of norepinephrine. They were however potentiated by treatment with desmethylimipramine which completely blocked the action of tyramine. A large amount of MnCl2 suppressed the actions of both papaverine and norepinephrine. Papaverine-induced negative chronotropic and inotropic effects were not influenced by atropine treatment. In addition, papaverine slightly potentiated the negative chronotropic and inotropic responses to adenosine. From these results, it appears that papaverine has a direct stimulating property on sinus rate and atrial contractility which may be due to inhibition of phosphodiesterase and successive accumulation of cyclic AMP. Moreover, papaverine may partially cause catecholamine release from adrenergic nerve fibers and it may inhibit the adenosine uptake mechanism.


Studies on drug-induced neuropathies. III. Motor nerve deficit in cats with experimental acrylamide neuropathy. To assess motor nerve and motor nerve terminal function in acrylamide neuropathy, cats were given i.m. injections of acrylamide (15 mg/kg) daily for 10 days to induce a peripheral neuropathy. Tests of function were performed on the day of the 10th injection (day 0) and 7, 21 and 35 days thereafter. In untreated animals tetanic conditioning evoked stimulus-bound repetition (SBR) in 85% of soleus alpha-motoneurones. Following administration of acrylamide, the  percent of axons elaborating SBR were: day 0 -- 79%, day 7 -- 71%, day 21 -- 31%, day 35 -- 22%. The response of soleus muscle to SBR is normally a post-tetanic potentiation (PTP) of contractile tension which is proportional to the tetanic conditioning frequency; during the development of the neuropathy, PTP in response to all tetanic frequencies progressively declined, concomitant with and as a result of the declining incidence of SBR. These data indicate that initial functional alterations in motor nerves during acrylamide neuropathy occurs at the level of the nerve terminal, preceding alterations in conduction velocities in the axons. However, the motor nerve deficit is not adequate, in either time to onset or severity, to account for the clinical manifestations of the neuropathy. The possible contribution to clinical signs of the neuropathy made by lesions to other peripheral nerves is discussed.


Effect of nomifensine on acetylcholine and choline in the rat striatum and brainstem. Nomifensine, at a dose of 40 mg/kg, slightly but significantly increased rat striatal acetylcholine 60 min after i.p. administration without affecting choline levels or choline O-acetyltransferase and cholinesterase activities. This drug had no effect on brainstem acetylcholine. In contrast, d-amphetamine and desipramine both produced a small but significant increase in brainstem acetylcholine. It is suggested that nomifensine increased striatal acetylcholine indirectly through blockade of dopamine uptake.


Central hyperglycemic effect of carbachol in rats. Intraventricular injection of carbachol produces hyperglycemia in rats at doses which are ineffective when given subcutaneously. This effect is suppressed by intraventricular administration of small amounts of atropine, further supporting the suggestion that the effect of carbachol is due to its action on central cholinergic receptors. Carbachol-induced hyperglycemia is not abolished by adrenalectomy and hypophysectomy, or pretreatment with reserpine.


Fenfluramine: long-term reduction in brain serotonin (5-hydroxytryptamine). A single oral dose of 15 mg/kg of fenfluramine reduced the level of serotonin in rat brain to 48, 51 and 63% of control at 1, 15 and 30 days, respectively, after administration. 3 mg/kg p.o. of the drug caused a smaller but significant diminution in brain serotonin. At the 3 mg/kg dose level, the decreases in serotonin were, at least partially, cumulative following multiple injections spaced 24 hr apart. Brains removed 14 days after the 5th daily injection of 5 mg/kg p.o. of fenfluramine had only 60% of the concentration of serotonin found in brains from control animals. These findings demonstrate that fenfluramine has a long-lasting action on serotonin-containing neurons in brain.


Acute gastric ulcer formation in response to electrical vagal stimulation in rats. Intermittent electrical stimulation of the left cervical vagus increased intragastric pressure and induced a 100% incidence of haemorrhagic ulcers in the glandular mucosa of rat stomachs. Atropine pretreatment of sub-diaphragmatic vagotomy prevented these effects. The findings substantiate the idea that stress-induced glandular ulcers result from vagal-mediated increased gastric contractions.


Ethanol, indomethacin and gastric acid secretion in the rat. In the anesthetized rat, 10% ethanol in the gastric lumen causes a total cessation of the secretion of gastric acid within 30--60 min. This effect is inhibited by pretreatment with indomethacin, which is a potent inhibitor of prostaglandin synthesis. Therefore, the inhibitory effect of local ethanol on gastric acid secretion in the rat may be mediated, at least partly, by increased synthesis of prostaglandins.


Release of 3H-alpha-methyl-m-tyramine from rat striatum in vitro. Release of 3H-d-alpha-methyl-m-tyramine (3H-MMTA), a false dopaminergic transmitter, from rat striatum was studied in vitro. After its initial uptake, 3H-MMTA was released by high K+ and by amphetamine. The release requirements were essentially the same as those known to exist for release of dopamine in vitro. These studies indicate that 3H-MMTA might serve as a useful tool with which to study dopamine release mechanisms in vitro.


Role of DA in the stimulant effect of DITA in mice; comparison with d-amphetamine. The effect of DL-alpha methyltyrosine (alpha-MT), 6-hydroxydopa (6-OH DOPA), haloperidol, phenoxybenzamine and propranolol on the stimulant activity of the anorexigenic agents (3',4'-dichloro-2-(2-imidazolin-2-yl-thio)-acetophenone HBr) (DITA) and d-amphetamine was studied in male mice. The pretreatment of mice with alpha-MT, (32, 64 mg/kg i.p.), significantly reduced the increase in motor activity induced by DITA or d-amphetamine. On the other hand, pretreatment of mice with 6-OH DOPA, (100, 150 mg/kg, i.v.), did not significantly after the stimulant effect of either DITA or d-amphetamine. In the case of haloperidol, it significantly reduced the increase of motor activity induced by DITA or d-amphetamine; propranolol and phenoxybenzamine were ineffective. Our results support the hypothesis that the stimulant effect of DITA and d-amphetamine depends mainly on the integrity of the central dopaminergic rather than the noradrenergic system.


Comparative action of fenfluramine on the uptake and release of serotonin and dopamine. The anorectic agent, fenfluramine, proves to be a good inhibitor of serotonin uptake in vitro, in synaptosomes from rat whole brain (IC50 = 8.5 +/- 0.6 X 10(-7) M). After administration in vivo, its inhibitory activity in vitro equals that of chlorimipramine and in contrast to the latter, its effect is of long duration. Fenfluramine is also effective in promoting the release of serotonin from pre-loaded synaptosomes. In comparison, the structurally related compound, amphetamine, has little activity with respect to these serotonin mechanisms. It is, however, active both in inhibiting the uptake of dopamine and in promoting its release, whereas fenfluramine is inactive. The implication of these mechanisms in the serotonin-depleting capacity as well as in the anorectic activity of fenfluramine is discussed.


Anticonvulsant activity of delta9-tetrahydrocannabinol compared with three other drugs. Delta9-tetrahydrocannabinol (THC) was compared with diphenylhydantoin (DPH), phenobarbital (PB) and chlordiazepoxide (CDP) using several standard laboratory procedures to determine anticonvulsant activity in mice, i.e., the maximal electroshock test (MES), and seizures induced by pentylenetetrazol, strychnine and nicotine. In the MES test, THC was the least potent and DPH the most potent blocker of hind limb tonic extensor convulsions whereas THC was the most potent and DPH the least potent in increasing the latency to this response and in preventing mortality. Seizures and mortality induced by pentylenetetrazol or by strychnine were enhanced by THC and DPH and were blocked by PB and CDP. In the test with nicotine, none of the four anticonvulsant agents prevented seizures; DPH was the only one which failed to increase latency; THC and DPH were less potent than PB and CDP in preventing mortality. THC most closely resembled DPH in the tests with chemical convulsant agents, but a sedative action of THC, resembling that of PB and CDP, was indicated by low ED5 0 for increased latency and for prevention of mortality in the MES test.


Aporphines. 16. Action of aporphine alkaloids on locomotor activity in rats with 6-hydroxydopamine lesions of the nucleus accumbens. (-)-Apomorphine and (+/-)-N-n-propylnorapomorphine (+/-)-NPA) produce stereotypy but not locomotor activity in normal rats. In rats with selective bilateral lesions of dopamine terminals in the nucleus accumbens induced by microinjection of 6-hydroxydopamine both compounds produced a marked stimulation of locomotor activity. (+/-)-NPA was considerably more potent than (-) -apomorphine. The maximal intensity of stimulation produced by the two drugs was, however, similar. The locomotor stimulant effects of (-)-apomorphine were inhibited by (+)-bulbocapnine (20 mg/kg) or pimozide (0.5 mg/kg). (+/-)-N-n-Propylnorapocodeine also produced a long-lasting stimulation of locomotor activity. (+/-)-Aporphine, (+/-)-isopomorphine, (-)-1,2-dihydroxyaporphine, and (-)-nuciferine were all inactive in stimulating locomotor activity.


[Fuorometric analysis of delta-9-tetrahydrocannabinol and its metabolites in urine]. The high number of drug addicts using marijuana (Cannabis sativa var. indica) under various forms has lead research workers to propound many a method for the characterization and assaying of delta9-tetrahydrocannabinol (delta9-THC) and its metabolites in biological fluids. Some of them are based on labelled materials, radioimmuno-chemistry, gas chromatography alone or combined with mass spectrometry. No mention of a purely chemical method has been found in the literature, with the exception of characterizations using thin-layer chromatography and formation of dansylated derivatives (5 to 9, 11 to 14, 16, 17, 18, 22, 23, 26, 31, 32, 34, to 38, 43 to 48, 59).


[Bromide vegetating skin diseases after treatment by a bromocalcic specialty]. The authors report on a case of vegetating bromoderma observed after therapy with bromocalcic speciality (Calcibronat). Repeated bromine determinations in body fluids enabled, while reconsidering the metabolism of this halogen, to monitor its elimination.


[Lactic acidosis induced by excessive ingestion of metformin]. The authors report on a case of lethal lactate acidosis during acute metformine and barbiturate poisoning. The study of energetic substrates and glucoregulation hormones demonstrated a blockade of hepatic gluconeogenesis.


Role of the kidneys in thrombopoietin production. Extracts of plasma from normal rats, rats injected with rabbit anti-rat platelet serum (RARPS), nephrectomized rats and nephrectomized rats injected with RARPS were tested in thrombocytotic mice for the presence of thrombopoietin. Only fractions of plasma from unoperated rats that had been made thrombocytopenic by injection of RARPS gave positive results for thrombopoietin. The results suggest that the kidneys play a role in thrombopoietin production.


Cerebello-olivary fibers: their origin, course and distribution in the North American opossum. Although degeneration techniques suggest that cerebello-olivary fibers are limited in their origin and distribution, horseradish peroxidase and autoradiographic experiments make it clear that they arise within all cerebellar nuclei and project to most, if not all, areas of the contralateral inferior olive. Autoradiographic preparations show that cerebello-olivary fibers are highly ordered and suggest that the dentate nucleus projects primarily to the principal olive, the interpositus anterior relays particularly heavy to the dorsal accessory nucleus and the interpositus posterior distributes extensively to the medial accessory complex. Evidence for a small projection from the fastigial nucleus to the caudal medial accessory nucleus is also available. However, it appears clear that neither the dentate nor the interpositus nuclei project to just one subdivision of the olive. For example, although dentate fibers end extensively within the principal nucleus some of them also distribute to portions of the medial accessory nucleus and perhaps the dorsal accessory nucleus as well. The medial accessory olive is particularly complex and at rostral levels receives input from both interposed and dentate nuclei, whereas more caudally it receives a projection from the fastigial nucleus. Olivary fibers from both the interposed and dentate nuclei traverse the brachium conjunctivum descendens and distribute primarily to the rostral 2/3 to 3/4 of the olive, whereas those from fastigial neurons take a different route and end more caudally. Experiments utilizing horseradish peroxidase as a retrograde tracer suggest that cerebello-olivary fibers from both the interpositus anterior and dentate nuclei take origin from a population of generally small neurons.


The role of cutaneous afferents from the distal hindlimb in the regulation of the step cycle of thalamic cats. The pad and the plantar surface of the foot were stimulated electrically in thalamic cats. Weak stimulation evoked an extensor reflex in the animal at rest. The same stimuli in a spontaneously walking animal applied during the stance phase produced an increase both in amplitude and duration of the ongoing extensor activity. When given during the swing phase, the stimuli either prolonged the ongoing flexor activity and/or shortened the following extensor burst. These changes in flexor and extensor burst duration were reflected in changes in the step cycle duration. Similar results were seen with direct stimulation of the sural nerve. For the latter experiments the ipsilateral hindlimb was fixed and denervated except for the ankle extensors and flexors, which showed rhythmic contractions correlated normally with the walking movements of the three remaining limbs. At rest, threshold stimulation of the sural nerve evoked a reflex contraction in the triceps surae of the fixed leg. The same stimuli applied during the contraction phase of the fixed triceps surae during walking resulted in a larger and longer extensor contraction and a delay of the following flexion. Stimulation during the relaxation phase of the fixed triceps surae reduced the duration of the following contraction phase. The findings are discussed in relation to the possible role of cutaneous input during locomotion.


Pathways for the vestibulo-ocular reflex excitation arising from semicircular canals of rabbits. In anesthetized albino rabbits, ampullary branches of the vestibular nerve were stimulated electrically. Prominent and stable reflex contraction was induced in extra-ocular muscles by applying single current pulses of relatively long duration, 3-5 msec. Survey with a glass microelectrode revealed that, during application of relatively wide pulses to a canal, primary vestibular fibers discharged impulses repetitively at a rate as high as 300-1400/sec and that after being transmitted across second-order vestibular neurons these impulses built up summated EPSPs in oculomotor neurons, large enough to trigger off motoneuronal discharges. From each semicircular canal, prominent reflex contraction was evoked selectively in two muslces; from the anterior canal in the ipsilateral superior rectus and contralateral inferior oblique; from the horizontal canal in the ipsilateral medial rectus and contralateral lateral rectus; and from the posterior rectus. Acute lesion experiments indicated that signals for this excitation reached IIIrd and IVth nuclei via three different pathways; from the anterior canal through the ipsilateral brachium conjunctivum, from the horizontal canal through the ipsilateral fasciculus longitudinalis medialis and from the posterior canal through the contralateral fasciculus longitudinalis medialis.


Postsynaptic inhibition of oculomotor neurons involved in vestibulo-ocular reflexes arising from semicircular canals of rabbits. In anesthetized albino rabbits, electric stimulation of vestibular nerve branches innervating semicircular canals produced not only reflex contraction in certain extraocular muscles, but also a transient relaxation in others. From relaxing muscles was recorded a slow muscle potential that reflected depression of spontaneous spike discharges in muscle fibers. When recorded monophasically, spontaneous spikes of muscle fibers were superposed to form a direct current potential, and depression of the spikes resulted in a transient reduction of this direct current potential, i.e., the slow muscle potential. The slow muscle potential was correlated to the postsynaptic inhibition induced in oculomotor neurons through the vestibulo-ocular reflex are for the following reasons; its latency was compatible with that of the IPSP's recorded from oculomotor neurons; it was removed by severing axons of the inhibitory second-order vestibular neurons; it was blocked by intravenous injection of picrotoxin as were the IPSP's in oculomotor neurons. By recording slow muscle potentials, a specific canal-muscle relationship for the vestibulo-ocular reflex inhibition of oculomotor neurons was shown to be complementary to that obtained for the vestibulo-ocular reflex excitation.


Variability of inter-spike intervals of cat's on-center optic tract fibres activated by steady light spot: a comparative study on X- and Y-fibres. Extracellular recordings were made from single on-center optic tract fibres in cats. Light spots of 10sec duration were focussed on the center of the receptive field under 1cd/m2 adaptation luminance by diffuse light. In the maintained discharges at 1 cd/m2, the shape of inter-spike interval histograms (IH) tended to be more skewed in X-fibres than in Y-fibres. As the luminance of the light spot increased, corresponding with the decrease in irregularity of length of inter-spike intervals, the shape of the IHs from X-fibres became symmetrical without noticeable shift of the modal interval peaks. This change was not clear in Y-fibres. The first order serial correlation coefficients showed small negative values in the case of the maintained discharges. These negative values increased with the decrease of the mean intervals of the discharges induced by the light spots, commonly in X- and Y-fibres. The negative correlation of adjacent inter-spike intervals was associated with a change of the shape of some IHs at lower luminances.


Gravity responses of Purkinje cells in the nodulus. In cats, either decerebrated or under chloralose anaesthesia, Purkinje cells (P-cells) of the cerebellar nodulus have been examined with the animal under static lateral tilt (roll +/- 20 degrees). The cell activity was extracellularly recorded and both "simple" and "complex" spike discharge patterns were studied. In 20 cells out of a population of 198, "simple" spike firing was found to be affected by static roll. Ten cells had an alpha-type response, 8 a beta-type, while only single examples of gamma and delta activations were found. Out of 67 Purkinje cells tested for "complex" spike activation, 5 were found to be sensitive to static roll, 4 with an alpha or beta response and one with a gamma response. The results are to be attributed to pure otolith activation and show that this input is able to modulate P-cell activity in the nodulus through both the mossy fibre and the climbing fibre systems.


Heterogeneity of motor units activating single Golgi tendon organs in cat leg muscles. The aim of this study was to investigate whether an individual Golgi tendon organ can signal the contraction of motor units with different physiological properties. The axonal conduction velocity and tetanic tension of motor units were examined in four muscles of the cat leg (peroneus brevis, peroneus longus, tibialis anterior and soleus). The motor units which were found to activate a given tendon organ had contractile properties dispersed over the same range as those of the whole muscle population. The proportion of tendon organ-activating motor units found in the studied samples suggests that altogether, the Golgi tendon organs of a muscle monitor the contraction of every motor unit in this muscle.


Electrophysiological studies on the cerebellocerebral projections in monkeys. 1. Responses evoked by stimulation of the cerebellar and thalamic nuclei were recorded by microelectrodes introduced at various depths in the cerebral cortex of monkeys (Macaca mulatta) under light Nembutal anaesthesia. 2. Stimulation of the medial (fastigial) cerebellar nucleus produced, at a latency of 4-5 msec, deep thalamo-cortical (T-C) responses (surface positive-deep negative potentials) mainly in the medial part of the precentral gyrus (area 4, "motor area for hindlimb") and in the superior parietal gyrus (area 5) on both contralateral and ipsilateral sides to the nucleus stimulated. 3. Stimulation of the lateral (dentate) cerebellar nucleus elicited, at a latency of about 3 msec, superficial T-C responses (surface negative-deep positive potentials) predominately in the lateral part of the precentral gyrus (area 4, "motor area for forelimb and face") and in the rostromedial part of the gyrus (area 6, premotor area) on the contralateral side. 4. Stimulation of the interpositus cerebellar nucleus set up superficial T-C responses chiefly in the motor area between those influenced by the medial and the lateral cerebellar nucleus stimulation and also in the premotor area on the contralateral side. 5. The respective areas responsive to the medial, interpositus and lateral nucleus stimulation overlapped considerably each other in the motor cortex. 6. Comparison of the responses in the cortex induced by stimulation of the cerebellar and thalamic nuclei indicated different relay portions in and around the VA-VL region of the thalamus for the superficial and the deep T-C responses respectively. 7. Functional implications of the results were discussed in referring to the cerebellocerebral projections in cats.


Ascending long spinal actions on forelimb motoneurons in the acute spinal cat. Ascending long spinal reflex system were investigated by means of monosynaptic reflex testing in the acutely spinalized unanesthetized cat. 1. Hindlimb nerve stimulation gave bilateral facilitatory effects on the motoneuron pools of pectoralis major and physiological flexors of the forelimb such as biceps brachii, extensor carpi radialis, extensor digitorum communis, but elicited depressive effects on the physiological extensors such as triceps brachii, flexor carpi radialis, flexor digitorum profundus. 2. In the latissimus dorsi, which is the antagonist of pectoralis major, a depressive effect was elicited by the stimulation of ipsilateral hindlimb nerves, and a facilitatory effect by contralateral stimulation. 3. These effects were evoked mainly from group II afferent fibers in muscle as well as cutaneous nerves. 4. Intracellular recordings from motoneurons of extensor carpi radialis revealed EPSPs following stimulation of hindlimb nerves with time courses corresponding to those of the facilitatory effects. We failed to detect any potential changes in the motoneurons of flexor carpi radialis following stimulation of hindlimb nerves.


Photodegradable formulatins of DDT.

Photodegradable formulatins of DDT. The incorporation of diphenylamine and diethylaniline in commercial DDT-WDP formulations sprayed on Phaseolus aureus and Tabernaemontana coronaria revealed that both these chemicals enhanced the initial rate of loss of DDT. Both these sensitizers exhibited no immediate adverse effect on the storage stability, pH, sieve requirement and colour of the formulations and introduced no phytotoxicity. Diphenylamine addition, however, had some adverse effects on the suspensibility.


A possible chemical basis for the higher mutagenicity of marijuana smoke as compared to tobacco smoke. The results of comparative anslyses of polynuclear aromatic hydrocarbons in marijuana and tobacco smoke indicate a considerably higher content of potential carcinogens in the former. A model experiment involving delta9-tetrahydrocannabinol suggests that the pyrolysis products of cannabinoids are major contributors to the polynuclear aromatic hydrocarbons.


Double stranded ribonuclease activity in human lymphocyte nuclei. Ribonuclease activity directed against the synthetic duplex polyrC:polyI was detected in nuclear extracts from both unstimulated and PHA-stimulated human lymphocytes. In the latter cells, the activity was about twice that of small lymphocytes.


Dissociation-constants of metat-ion-complexes with alkaline phosphatase from pig kidney. Using metal-ion buffers it was possible to remove Zn2+, Mg2+ and Mn2+ ions of pig kidney alkaline phosphatase reversibly. The dissociation constants obtained are KEMg: 4 X 10(-7) M, KEMn: 4 X 10(-8) M and KEZn: 8 X 10(-13) M (22 degrees C, pH: 9.6, mu: 0.07).


Age and peritoneal fluid cellular distribution in women 20-40 years of age. Cytologic aspiration specimens of peritoneal fluid revealed that mesothelial cell proportions were significantly reduced 19.2% in women between 26 and 35 years of age. Possibly, mesothelial cell renewal was decreased in women of the older age groups.


Biochemical markers in the taxonomy of the Actinomycetales. Useful biochemical markers for the classification of Actinomycetales are: 1. DL- or LL-diaminopimelic acid in the peptidoglycan, 2. sugar composition of polysaccharides, 3. fatty acid spectrum of cell lipids. The occurrence of various kinds of branched fatty acids and of unsaturated fatty acids is of special value.


Emericid, a new polyether antibiotic from Streptomyces hygroscopicus (DS 24 367). Emericid is a new polyether polycyclic ionophore antibiotic excreted by Streptomyces hygroscopicus (DS 24 367). Active in vitro against Gram-positive bacteria, it is ineffective in vivo. At a 0.006-0.02% level in the diet it protects chickens and rabbits against coccidiosis.


Cellular control of the tick-borne virus antigen production in persistently infected cell culture. The influence of inhibition or stimulation of cellular DNA synthesis on tick-borne virus antigen production in persistently infected cell culture was studied. Either mitomycin C or cytosine-arabinoside caused cessation of antigen-containing cell number increase. Stimulation of cellular DNA synthesis by growth medium change increased the level of antigen-containing cells. When HEp-2-Sof culture was synchronized, a correlation was observed between the entrance of cells into DNA synthesis phase and the increase of proportion of antigen-containing cells.


Effect of air ionization of blood serotonin in vitro. The effect of negative and positive air ionisation on siliconized blood serotonin was studied in vitro. The experiments showed that within 10 min positive ionisation increased serotonin levels in total blood (+40%), plasma (+90%), erythrocytes (+50%) and thrombocytes (+240%). On the other hand, negative ionization (10 min) lowered the serotonin content of total blood (-30%), plasma (-42.5%), erythrocytes (-41.7%) and thrombocytes (-72.3%), thus confirming the 'Krueger Effect' in vitro.


[Amino acid incorporation by human milk fat globules membranes (author's transl)]. Human milk fat globule membranes (MFGM) can incorporate radioactive 14C amino acids in a hot trichloracetic acid-insoluble material. Aspecific adsorption and bacterial contamination are unlikely. The products of protein synthesis were analyzed by polyacrylamide gel electrophoresis in sodium dodecyl sulfate or by action of proteolytic enzymes. Various inhibitors of protein synthesis were assayed. Fragments of rough endoplasmic reticulum or mitochondria could be involved in this incorporation.


Alternative methods of animal sacrifice: the effect on intestinal function in vitro. The total fluid uptake of everted sacs of rat jejunum was compared in animals killed by stunning and decapitation, or anaesthetised with ether. Fluid transport was significantly higher in the tissue prepared from stunned and decapitated animals. It is suggested that etherization may have adverse effects on the physiological viability of subsequently isolated tissues.


Concerning the ionic basis of presynaptic inhibition. The superfused rat cuneate nucleus has been used to investigate the sensitivity of primary afferent terminals and of evoked primary afferent depolarization (PAD) to alterations in extracellular K+ and Cl- ions levels. Results indicate that PAD is caused by an efflux of Cl- from primary afferent terminals rather than by an increase in extracellular K+.


Effect of angiotensin II on neonatal lamb carotid arteries. Isometric tension was measured in arterial strips from neonatal lambs and adult sheep, after stimulation by angiotensin II. During the early maturation period immediately following birth (3 weeks) there was a progressive increase in sensitivity to the agent.


Sodium pump: its importance to intercellular communication in heart fibres. The effect of ouabain on the electrical coupling of canine Purkinje cells was investigated. It was found that the glycoside decreases cell communication through an increase in junctional resistance, what supports the view that the sodium pump has an important role on the control of cell communication.


Behavior and endocrine effects of 3,4,5-trimethoxyamphetamine in male mice. Effects of single doses of 50 and 100 mg/kg of TMA given i.p. were noted in male albino mice after 40 min and 2 1/2 h. Locomotor activity was significantly altered and biochemical tests indicated stimulatory effects on adrenocortical and adrenomedullary functions due to TMA.


Structure-activity relationships of cyclic acetylcholine analogues of the piperidinol and thiacyclohexanol series. The hydrochlorides and methiodides of 1-methyl-3- and 4-acetoxypiperidine and their sulphonium analogues are cholinergic agonists. They are substrates for acetylcholinesterase. The sulphonium compounds have a 78(-524)-fold higher activity than its nitrogen analogues.


The accumulation pattern of ingested gossypol in selected organs of the rat. Bound gossypol levels in the spleen and kidney of rats ingesting dietary gossypol (0.98%) varied directly with the feeding intervals of 6, 14, 28 and 35 days. Free gossypol level in the kidney, spleen and lungs increased for 14 days and then tended to decrease as the feeding period was extended.


Interaction of atropine or methylatropinium with four effects of two cholinergic drugs. In mice, pilocarpine - or oxotremorine - induced decrease in locomotor activity and increase of the reaction time to pain were antagonized by atropine and not by methylatropinium. Identical doses of atropine and methylatropinium suppressed the antagonism of the cholinergics towards reserpine-induced palpebral ptosis. Cholinergics-induced hypothermia was not clearly antagonized by atropine or methylatropinium.


Melatonin antagonizes colchicine-induced mitotic arrest. Melatonin, in concentrations up to 10(-3) M, showed no effect on mitosis in cultures of HeLa or KB cells. However, when melatonin at 10(-4) M was preincubated with HeLa cells prior to addition of 10(-7) M colchicine, a reduction in the mitotic index, in comparison to colchicine alone, was observed.


Extrachromosomal DNA and RNA-synthesis in oocytes of Creophilus maxillosus (Staphylinidae, Coleoptera, Polyphaga). It has been found that the transcriptional activity of nuclear extra DNA in Creophilus maxillosus oocytes, as examined by autoradiography, increases parallel with its dispersion during the previtellogenic period of oocyte growth. The RNA, after being synthesized in the greatly enlarged oocyte nucleus, is subsequently transported into the cytoplasm. The oocyte chromosomes form a karyosphere and synthesize the RNA more weakly than other parts of the nucleus, which contain the extra DNA in a highly dispersed condition.


The distribution of endocrine-like cells in the human male and female urethral epithelium. Histochemical and electron microscopic techniques have been used to study the nature and distribution of fluorescent, endocrine-like cells in the urethra of the human male and female. The confinement of such cells to specific regions of the urethra is discussed in relation to the embryological development of this part of the urinary tract.


Cytochemical evidence for stage-specific changes of nuclear RNA and nonhistone protein content during early development of Triturus vulgaris. During early embryogenesis of Triturus vulgaris, RNA and nonhistone protein contents of neuroectoderm nuclei change with stage specifically. Maximum values were found in the late gastrula after embryonic induction, and in the late neurula with the formation of the neural tube. The stage-specific increases of RNA and nonhistone protein are correlated with a preceding increase of Feulgen-DNA content.


Coated vesicles in the rat adrenal glomerular zone after a low-sodium diet. In rats subjected to a low-sodium diet, a great activity was observed of the coated vesicles at Golgi complex and cell surfaces of glomerular adrenal zone. These findings are related to the function of these organoids in the uptake and transport of necessary substances under stimulating conditions of the zone.


Effect of haemolysis on plasms and serum immunoglobulin estimations. Plasma IgG, IgM and IgA estimations were carried out in blood samples with varying degrees of haemolysis, produced by controlled ultrasonication. Extent of haemolysis was determined by plasma haemoglobin, plasma potassium and packed cell volume; and plasma IgG, IgM and IgA estimations showed a steady and significant fall with increasing haemolysis. A calculated correction is proposed which compensates for the dilutional effect of haemolysis, during estimations of plasma and serum immunoglobulins.


Undulating tubules in lymphocytes of an apparently healthy human donor. So-called 'undulating tubules' were found in the blood lymphocytes of an apparently healthy 33-year-old male. Undulating tubules have been noted to occur frequently in kidney cells and blood lymphocytes of patients suffering from collagen diseases and especially from SLE. They have been suggested to be a possibly pathognomonic finding in such diseases. Our result seems to contradict such an association.


Effect of estradiol on aminoacid incorporation into proteins of different hypothalamic areas in prepuberal rats. Estradiol in vitro produces a significant increase in the incorporation of 3H-leucine into proteins of the anterior hypothalamic area in prepuberal female rats, 15 and 20 days old, but not in younger animals. The ovarian hormone induced no changes in the protein synthetic activity of middle and posterior hypothalamus and cerebral cortex in prepuberal female rats of different ages. Estradiol did not modify the protein synthesis of the hypothalamus and cerebral cortex in prepuberal male rats.


Effect of the extracts from Aristolochia indica Linn. on interception in female mice. The crude petroleum ether, chloroform and alcoholic extracts from the roots of Aristolochia indica (Linn.) showed 100% interceptive activity in mature female mice at the single dose of 100 mg/kg body wt. The follow-up studies with the chloroform extract showed the most significant effect in the basic part and two acidic fractions at the single dose levels of 50 mg/kg body wt. No toxic effect was observed at the dose levels used.


Granulocyte colony formation in vitro: enhancement by human placental (umbilical cord) serum. Addition of human placental umbilical cord serum to bone marrow cultures reproducibly increased the number of granulocyte colonies in vitro. This stimulatory effect was significantly greater than that of fetal calf serum which was seen in cultures of human bone marrow under the conditions described.


[Influence of immobilization and 3(beta-aminoethyl)-1, 2, 4-triazole on the calcium level in the tissues of the stomach of guinea pigs during the formation of experimental ulcers]. The Ca2+ ions content in the blood plasma and gastric tissues of guinea pigs during experimental ulceration provoked by a 12-hour immobilation or through introduction of 3(beta-aminoethyl)-1,2,4-triazol--a histamine analogue--was measured by using atom absorption spectrophotometry. A sharp fall in the concentration of calcium in gastric tissues upon immobilization down to 79 per cent (317 gamma/g) and after administration of the histamine analogue--down to 71 per cent (287 gamma/g. Similar shifts were seen to occur in the blood plasma as well. According to the authors this implies that under the effect of different action the tissular dystrophy develops by following a common mechanism with involvement not only of the adenylcyclase system, but of the calcium ions metabolism as well.


[Synthesis of analogues of acetohydroxam lacetic acid with phytotoxic activity]. Syntheses, spectroscopic data and phytotoxic activities of some N-acyl-O-alkylhydroxylamines, similar in structure to the natural compoud, methyl acetohydroxamyl acetate, are reported. Many of synthesized compounds show strong growth-inhibiting activity on both roots and coleoptiles of Triticum vulgare seedlings.


Preparation and spectroscopic behavior of acetylderivatives of sulphonamides. Acetylderivatives of five sulpha drugs (N1-phenylsulphamilamide, sulphapyridine, sulphapyrimidine, sulphamerazine, sulphamethazine) and of three reference compounds, devoid of the para amino group, are synthetized. The trends of the U.V. spectra and of the symmetric stretching frequency of the SO2 group of the prepared compounds are described and discussed in a systematic way, by means of a simple conjugation model. Our data show that, on the basis of the values of the indices of electronic structure [upsilons(SO2), lambdap], the N1-acetylderivatives would appear to have a lower bacteriostatic activity than that of the non-acetylated compounds, which is in disagreement with the literature. The question therefore arises as to whether the N1-acetylderivatives are to be considered an exception to the structure-activity correlations previously put forward, or whether, owing to phenomena of hydrolysis, the degree of activity can no longer be attributed to the form characterized by the indices measured.


2,6-dialkylpiperazines. VII-Synthesis of N4-(2'-pyridyl)-2,6-dimethylpiperazine and separation of its geometrical isomers. Cis-(I a) and trans-(I b) N4-(2'-pyridyl)-2,6-dimethylpiperazine were synthetised as the key intermediates for isomeric 2,6-dimethylpiperazine derivatives to be pharmacologically tested.


[Influence of octadine, reserpine and methyl-dopa on the hemodynamic system]. In experiments set up on rats the influence of octadine (sanotensin), reserpine and methyl-dopa on the basic characteristics of the systemic hemodynamics in persistent renovascular hypertension was studied. The nature of the influence exerted by the above drugs on the systemic hemodynamics of hypertensive rats is shown to depend upon the duration of their action on the organism. The hypotensive effect manifests itself first by reduced cardiac ejection and then by a fall of the total peripheral resistance. It is presumed that the disappearance of the inhibitory action of octadine, reserpine and methyl-dopa on the cardiac ejection is related to the development of a compensatory reaction aimed at maintaining the needed level of the blood supply to the organs and tissues--i. e. at "systemic autoregulation".


Alkylthiophenylureas with phytotoxic activity. A series of 1-(p.alkylthio)phenylureas variously substituted on the N atom in position 3 (substances I leads to XXXVII) has been prepared and studied for pre- and post-emergence phytotoxicity. Some compounds were found to have high activity; in particular some 1-(p.alkylthio)phenyl-3-dimethylureas showed high activity even at very low doses (2 kg/ha).


[Research on heterocyclic compounds. II.- Imidazo ( 1,2-a) pyridin-2-acetic acids]. A series of ethyl imidazo [1,2-a]pyridin-2-acetates was prepared by reaction between several substituted 2-aminopyridines and ethyl-4-bromoacetate. From these esters the corresponding acids were prepared and their anti-inflammatory activity was tested.


Cholinergic compounds VII - Synthesis and pharmacological activity of some trimethylammonium iodides related to desethermuscarine. Some substances similar to desethermuscarine were synthesized and studied as cholinergics on isolated organs. The results show the importance of the cyclopentane nucleus with regard to activity. The activity of 3-methyltrimethylammonium hexane iodide is particularly interesting for, though lacking the oxygenated function in 3 and having a different methyl spatial arrangement, this compound is only ten times less active than desethermuscarone.


Determination of structure-activity relationships of 2-aryl-1,3-indandiones. The uncoupling activities in rat liver mitochondria of a number of 2-aryl-1,3-indandiones were studied by means of the Free-Wilson method followed by a stepwise regression analysis. The activity appears to be mainly dependent on the hydrophobic parameter.


Laparoscopic sterilization with electrocautery, spring-loaded clips, and Silastic bands: technical problems and early complications. Among 2283 patients, rates of technical failure, technical difficulty, and operative and early postoperative complications were evaluated for different methods of tubal occlusion at laparoscopy: electrocoagulation (980 cases), spring-loaded clip application (991 cases), and Silastic band application (312 cases). Rates of technical failure and technical difficulty at surgery were significantly higher (P less than 0.05) for the spring-loaded clip technique than for the electrocoagulation and Silastic band techniques. Mechanical and optical difficulties with the prototype spring clip applicator were the major sources of technical difficulties. Rates of operative (1.2%) and early postoperative (1.9%) complications were not significantly different for the three techniques of tubal occlusion. It is concluded that all three study techniques appear to be practical, and large, long-term, randomized, comparative studies to determine rates of failure and subsequent gynecologic problems are necessary to determine the best method of sterilization.


Some gross observations of the epididymides following vasectomy: a clinical study. In 114 vasectomized men, 220 epididymides were grossly examined during vasovasostomy. Fullness, distention, turgidity, thickening, induration, and other gross changes of the epididymides, including the formation of cystic spermatic granuloma, or spermatocele, indicated inadequate removal of spermatozoa and testicular fluid from the sequestrated proximal seminal ducts and the epididymis. Further studies are necessary to determine whether the epididymal changes following vasectomy have any effect on sperm morphology and sperm physiology. The information obtained from these studies possibly may explain the poor pregnancy rates in the spouses of successfully vasanastomosed patients.


Anatomical sizes of the human vas deferens after vasectomy. After vasectomy, the lumen of the testicular side of the vas deferens dilates, apparently because of internal pressure from accumulation of spermatic fluid. This dilatation occurs within the 1st postoperative year. It causes a thinning of the wall of the vas without significant increase in the external diameter. The extent of dilatation is similar in the same man, but differs markedly between individuals, the mean increase in diameter being approximately 70%. The implications of this difference in size are discussed with regard to vas anastomosis and to the possible use of devices to rejoin the vas or to bridge a defect created by a prior vasectomy.


Comparison of the tray agglutination technique with the gelatin agglutination technique for the detection of spermagglutinating activity in human sera. Extensive comparisons were made between the tray agglutination test (TAT) and the gelatin agglutination test (GAT) in order to evaluate the validity of the TAT for demonstrating spermagglutinating activity in human sera. The incidence of spermagglutination in both tests was about the same. In screening 118 samples from infertile men and women, the TAT seemed to be more sensitive, whereas the reverse was true when 143 samples earlier found positive with the GAT were tested. These differences were mainly encountered with low titers. Two T-agglutinating sera (or 2% of the sera) with a GAT titer of 16 or more (both had a titer of 64) were missed with the TAT. On the other hand, two sera (or 2% of the screened samples) having small H-agglutinates up to a titer of 32 to 64 were positive only with the TAT.


Some properties of human endometrial alkaline phosphatase. A study of some biochemical properties of alkaline phosphatase derived from human endometrium has been undertaken. The endometrial enzyme has been shown to be different from alkaline phosphatases obtained from placenta and small intestine. Endometrial alkaline phosphatase is inhibited by sodium deoxycholate but not by L-phenylalanine; it is completely inhibited by 3 M urea. Magnesium ions have no significant effect on the endometrial enzyme. No differences in biochemical properties were observed when alkaline phosphatase from follicular phase endometrium was compared with that from luteal phase tissue. Acrylamide gel electrophoresis showed a single, constant band of enzyme at all stages of the cycle. It is concluded that, despite the cyclic appearance of alkaline phosphatase in endometrial glands and the constant presence of the enzyme in blood vessels, there is but one variety of alkaline phosphatase in human endometrium.


Studies of rabbit ovarian contractility using chronically implanted transducers. A chronically implanted, highly sensitive force transducer was used to study ovarian contractions in the rabbit. The transducer is implanted into the medulla of the ovary through its long axis. The leads are then drawn through the abdominal wall and directed subcutaneously to the back of the neck. The miniature pin connector is fixed into place beneath the skin to facilitate accessibility for repeated recordings, obviating the necessity for anesthesia or serial laparotomies. Intraovarian transducers were implanted in isolated rabbits. Serial recordings of ovarian contractions were made at weekly intervals for 3 weeks, following which ovulation was induced with 100 IU of human chorionic gonadotropin (HCG). Extended recordings were made from 3 through 13 hours after HCG administration to six animals. Recordings revealed increased ovarian contractile activity beginning just before the anticipated time of ovulation. The observations support those of previous acute experiments and demonstrate a relationship between ovarian contractile activity and the process of follicle rupture.


The sperm-cervical mucus contact test: a preliminary report. Infertility in men and women with spermagglutinins is the result of disturbed penetration and migration of spermatozoa in the cervical mucus. In ejaculates with partial spermagglutination caused by autoimmunization, the progressive propulsion of the sperm was changed into stationary, shaking movement the moment the sperm came into contact with cervical mucus. The same alteration in spermatozoal motility pattern also occurred when spermatozoa from a normal, fertile ejaculate came into contact with cervical mucus of a woman whose serum contained sperm antibodies. This shaking phenomenon was visualized in a simple test, the sperm-cervical mucus contact test. We demonstrated that sensitized spermatozoa exhibit the shaking phenomenon after contact with the glycoprotein fraction of the cervical mucus and not after contact with the aqueous fraction. Therefore, the hypothesis is introduced that the shaking phenomenon is due to an interaction between sensitized spermatozoa and the glycoprotein micelles in cervical mucus.


[An analysis of the electrical responses of the neocortex evoked by stimulation of different hypothalamic structures]. Evoked potentials and extracellular spike activity during stimulation of the posterior, lateral, anterior, and ventro-medical hypothalamus were recorded in different areas of the neocortex in unanesthetized cats. Hypothalamo--cortical evoked potentials (HC EP) of maximal amplitude are generated in gyr. sigm. ant. with 0.5--2.5 msec latency. The responses are of positive--negative configuration and often a fast spike--like defiction appears at the positive phase. EP in gyr. suprasylv. med. are initially negative and of 2--6 msec latency. Most effective is stimulation of the posterior and lateral hypothalamus, HC EP in gyr. sigm. ant. following the frequency of stimulation up to 200/sec and being characterized not only by a high "functional lability" or reproducibility but also by the ability of posttetanic potentiation. With the aid of paired stimuli, the early fast component of the EP in the sensorimotor cortex was shown to appear at an interval of approximately 2 msec. HC EP entirely recover 50--150 msec after the conditioning stimulus. The recovery cycle is biphasic and reflect, a biphasic change of the excitability of neurons in gyr. sigm. ant. and suprasylvian associative areas of the cortex. The latency of evoked discharges of some neurons of the sensorimotor cortex during stimulation of the posterior hypothalamus, is 0.8--1.5 msec, which suggests the existence of a monosynaptic pathway for the hypothalamo--cortical discharges. The maximal amount of neurons in deep layers of gyr. sigm. ant. respond during development of the early and the main positive deflections of HC EP.


[Neuronal organization of the thermosensory region of the anterior hypothalamus]. In anesthetized rabbits, extracellular recording of activity of 236 neurons was made in the anterior hypothalamus on changing of its temperature (+/-3 degrees C). 27% of the neurons revealed high sensitivity to the temperature stimulus with coefficient Q10 from 2.4 to 30; 6% of the neurons reacted by the on-response type; 5% of the neurons changed their activity and preserved the new level. The character of the unit responses seems to indicate that the anterior hypothalamus fulfills not only the reception of temperature shifts, i.e. the primary processing of information, but its further analysis as well.


[Responses of directionally sensitive neurons of the frog midbrain tectum, their adaptation and extrapolation responses]. The greatest coherence of responses and latency for neuronal pairs was found at interelectrode distances up to 300 microns which is due, apparently, to dimensions of the afferent fibers' branching areas. The adaptation and extrapolation features observed in majority of the neurons, were more obvious in the tectum nuclear layers rather than in the fiber those. The more stable responses of the fiber layers' neurons suggest a representation of branches stemming from the fibers of the retina ganglionic cells, while in the nuclear layers the elements with high adaptability: the "novelty neurons", are localized.


[Reflection of visceral signals in the impulse activity of the caudate nucleus]. Responses of spontaneously active neurons of the caudate nucleus to stimulation of the n. splanchnicus were extracellularly recorded in immobilized cats. Presence of multimodal neurons responding to stimulation of visceral, somatic and auditory sensory systems, was also determined in this structure. The data obtained suggest probable participation of the caudate nucleus' neurons in the mechanisms of interaction between visceral signals and somatic and auditory those.


[An analysis of participation of central noradrenergic structures in the process of memory trace reproduction]. Variations of the noradrenaline content in noradrenergic terminals of different nuclei of the limbic system and the anterior hypothalamus were studied by the limuniscent histochemical method in the course of reproduction of a series of conditioned reflex reacitions in male Wistar rats. Both in reproduction of a conditioned passive avoiding responce and in training with inevitable conditioned reinforcement, a decrease of the noradrenaline content was found as compared with the control level. A lesser decrease was observed both in the animals that had been trained but did not reproduce the relfex reaction, and in the trained animals after repeated testing for 4 days following the training. The reproduction of the conditioned active avoiding response in shuttle box did not entail variations in the noradrenaline content.


[Nystagmus after unilateral destruction of the superior colliculus in rabbits]. The frequency, the amplitude of optokinetic nystagmus (OKN) the reverse postoptokinetic nystagmus (RPN) were studied in rabbits before and during the first 7 days after left-side lesions of the superior colliculi. The lesions led to a more obvious decrease in the frequency and amplitude of the OKN than in those of the RPN. The retino-colliculi pathway seems to be of greater importance for the OKN formation than for the RPN mechanism.


[Characteristics of the reactions of neurons of successive links in the auditory pathway to changes in the timing of acoustic signals]. Afferent impulsation was compared for different levels of the auditory system: the cochlear nuclei, posterior colliculi, and the auditory cortex. While moving from the cochlear nuclei over to the posterior colliculi and the auditory cortex, the number of neurons describing the temporal structure of the amplitude-modulated signal's envelope in the impulse activity pattern, becomes sharply reduced; the number of neurons selectively responding to certain phases of the envelope increases; the firing rate of neurons of the auditory pathway's higher levels decreases; the repetition rates becomes narrow due to limitation from both the high- and the low-frequency sides. Selectivity of responses to combination of such signal parameters as the frequency of the carrier and the rhythm of the amplitude modulation, increases. Specificity of the neuronal responses increases on certain combinations of such parameters of the frequency-modulated sounds as the frequency range in the signal, the direction and speed of the frequency modulation. The data obtained revealed some general tendencies of the impulsation transformation in successive levels of the auditory pathway.


[The electrical reactions and lability of an isolated nerve exposed to low-energy laser radiation]. In the frog isolated n. n. ischiadici, under permanent low-intensity laser radiation (6328 A; 0.5 mVt), the physiological lability of tissue changed in a monophasic manner towards consecutive growth. After a single illumination lasting from 1 sec to 10 min, statistically significant shifts of the maximal rhythm of impulse excitation towards an increase occur with some "latency" at the 10-min exposure. The maximal frequency of evoked action potentials, at that, invariably remained at the attained level. After the laser action, the irradiated portion of the nerve becomes electropositive in regard to other, intact points of the nerve. The polarization shifts are weak and not directly dependent on the exposure dose of the irradiation. The laser is concluded to evoke an increase and acceleration of metabolic processes which raises the lability level, hence the increased working capacity of the tissue.