Lipid-linked oligosaccharides containing glucose in lactating rabbit mammary gland. 1. Microsomal fractions of lactating rabbit mammary gland incubated with UDP-glucose formed lipid-linked mono- and oligo-saccharides. The lipid-linked monosaccharide had chromatographic properties similar to those of dolichol phosphate mannose and yielded glucose on acid hydrolysis. 2. Incubation of the microsomal fraction with GDP-[U14C]-mannose yielded an oligosaccharide lipid of approximately seven monosaccharide units. Further incubation with UDP-glucose increased the size of the oligosaccharide by approximately two units. 3. Explants of lactating rabbit mammary gland incorporated [U-14C]glucose into both lipid-linked mono- and oligo-saccharides. The oligosaccharide lipid was of approx. 11 monosaccharide units. 4. Considerable redistribution of radioactive label occurred in the explant system, and radioactively labelled glucosamine and mannose, as well as glucose, were detected on acid hydrolysis of the oligosaccharide lipid. 5. Glucose was also detected in the acid hydrolysate of explant proteins. Radioactive glucosamine, galactosamine, galactose and mannose were also found in this fraction.


[Action of high temperature on the integrity of LS fibroblasts. I. Effect of culture in the presence of sucrose]. LS fibroblasts which have accumulated sucrose into cytoplasmic vacuoles during 4 days are more fragile than normal controls when they are exposed to temperatures between 45 degrees C and 60 degrees C. Continuing to cultivate for 6 more days in the presence of sucrose apparently improves the resistance of the vacuolated cultures to the damaging temperatures, possibly because of a selective enhancement of the more resistant cells.


[Action of high temperature on the integrity of LS fibroblasts. II. Effect of duration of presence in a medium containing sucrose]. The resistance to high temperatures of LS fibroblasts starts lowering quite rapidly when the cells have been suspended in a culture medium containing sucrose. On the other hand, transferring back to normal medium for increasing times cells cultivated for 4 days in the presence of sucrose seems to gradually improve their resistance.


[Histological and cytological studies of the inflammatory process induced by polyesters in the guinea pig]. The inflammatory process caused in the omentum of the guinea pig by the intraperitoneal injection of minced polyester threads is characterized by an increasing number of mononuclear and giant cells surrounding polyester fragments. Lymphocytes and plasma cells have been found to participate in the process when the animals are treated for longer times. The cells obtained from the peritoneal cavity have a large lysosomal apparatus as stained by acridine orange, although the colour is taken up to a lesser degree when the cells are in the presence of the polyester.


[Effects of lymphocyte stimulation in vitro of alkaline salts of some aroyl-hydrazino-carbodithioic acids and 1,3,4-oxadiazole derivatives: preliminary research]. The behaviour of alkaline salts of some aroyl-hydrazine-carbodithioic acids [comp. Ia,b,c,] and derivatives of 1,3,4-oxadiazole [comp. IIa,b,c, e IIIa,b,c] , has been studied, on the capability of lymphoblasts in vitro, in consequence of stimulation by some mitogen agents (PHA, PWM). It has been pointed out that the considered compounds inhibit the cellular mitosis in variable percentage in relation to their structure and to the used mitogen agent, frequently causing some mitogen-like morphological modification, also revealable under a optical microscope. The higher inhibition has been obtained by the Ic, IIc, and IIIc compounds, in which Ar is the 3,4-dihydroxymethylenephenyl radical, proving selective, in some cases, for the T lymphocytes.


Decision-making behaviour during inhalation of subanaesthetic concentrations of enflurane. The effect of subanaesthetic concentrations of enflurane on decision-making behaviour in risk situations was assessed using a signal detection task. The subject heard noise alone (white noise) or a signal superimposed on the noise (1000-Hz tone) and had to report what he heard in each trial. Risk situations were manipulated by changing the monetary reward and penalty associated with correct and incorrect responses. Eight male volunteers participated in this study. It was found that under anaesthetic influence they did not avoid the same risks which had been avoided under control conditions. The findings are explained in terms of influence of the gas on loss of control and lessened responsibility for the result of behaviour.


Effects of low concentrations of enflurane on probability learning. The effects of controlled subanaesthetic concentrations of enflurane on learning behaviour and on ability to change previously developed decision strategies were studied in 10 male volunteers, using a probability learning task. Subjects were instructed to predict on each of 200 consecutive trials, whether a left or a right light would appear. The appearance of lights was pre-determined by a set relative frequency unknown to the subject. The relative frequency was automatically changed at the end of the first 100 trials, from 8/10 lights in the left side to 4/10. It was found that enflurane at subanaesthetic concentration of 0.25% (end-tidal) slowed the rate of learning, and increased the number of trials required for readjusting the prediction strategy to the changed situation.


Preservation of the pulmonary vasoconstrictor response to alveolar hypoxia during the administration of halothane to dogs. The action of halothane on the pulmonary vasoconstrictor response to unilateral alveolar hypoxia was studied in two groups of dogs. In the first group the redistribution of blood flow between the two lungs was studied with a radioactive isotope method, which provided intermittent measurements, whilst in the second group the distribution of blood flow was observed continuously. In both groups there was no significant alteration of the hypoxic vasoconstrictor response with inspired halothane concentrations varying from 0.5 to 1.5%.


Lack of effect of morphine and buprenorphine on hypoxic pulmonary vasoconstriction in the isolated perfused cat lung and the perfused lobe of the dog lung. In an isolated perfused cat lung preparation and a perfused lobe of dog lung preparation a pressor response of the pulmonary circulation was elicited to alveolar hypoxia (5% oxygen). The magnitude of this reponse was not affected by either of the opioid drugs, morphine or buprenorphine.


Althesin infusion and regional blockade anaesthesia for major gynaecological surgery. The effects of an infusion of a 10% Althesin solution to induce sleep in patients undergoing major gynaecological surgery performed under extradural analgesia are presented. There was no significant depressant effect on the cardiovascular system, but a predictable and preventable depression of respiratory function. Liver function tests were unaffected by the infusion. Operating conditions were satisfactory in all patients and postoperative recovery was smooth and uncomplicated.


Extradural analgesia--the preferred method of analgesia for vaginal breech delivery. A prospective trial was designed to study the effect of extradural analgesia on the management of breech delivery. From a study of 51 patients, it was concluded that the duration of labour was not lengthened, the frequency of breech extraction was decreased and the condition of the infant was improved, as shown by foetal blood sampling and Apgar scores. Therefore we recommend strongly that extradural analgesia should be used in the management of all breech deliveries.


Pharmacokinetics of althesin--comparison with lignocaine. The plasma concentrations of alphaxalone were measured with a gas chromatographic technique in six patients following a single i.v. injection of Althesin, and in five volunteers following oral administration. A two-compartment open model was used in the pharmacokinetic analysis of the data, and the plasma clearance of alphaxalone was similar to the blood flow through the liver. A comparison with the pharmacokinetics of lignocaine was made.


Pharmacokinetics of thiopentone: effects of enflurane and nitrous oxide anaesthesia and surgery. Plasma concentrations of thiopentone following the injection of 3.5 mg kg-1 i.v. were studied in six patients who received enflurane and nitrous oxide anaesthesia and six volunteers. We identified a three-compartment open model system containing both a "shallow" and a "deep" peripheral compartment in all the patients and half of the controls, and a two-compartment open model for the remaining volunteers. The distribution of thiopentone to the tissues was very rapid, the alpha and beta distribution half-lives averaging 2.5 min and 46.4 min respectively for the patient group and 2.8 min and 48.7 min for the control group. The wide distribution of the drug was indicated by the apparent volume of distribution, the means of which varied between 2 and 1.5 times body weight. The mean elimination half-life was 5.1 h for the patients and 5.7 h for the volunteers. The return of the drug to the central compartment from the deep peripheral compartment was the rate-controlling factor in its elimination. Neither enflurane and nitrous oxide anaesthesia nor the stress of surgery affected the distribution or clearance of the drug from plasma.


Theatre ventilation. A comparison of design and observed values. The ventilation rates of 23 operating theatres were tested randomly. These were found to vary widely from design specifications (--43 to +40%). One modern theatre was studied intensively for 6 months and the causes of poor ventilation determined. Preventative maintenance schemes are justified by a positive relationship with plant performance. The influence of theatre ventilation of contamination with anaesthetic agents and the medico-legal implications of poor theatre ventilation are discussed. There is a need for main duct airflow signals, displayed in theatre, to warn personnel of low levels of theatre ventilation.


Penetration of colloidal carbon through post-capillary venules in lymph nodes and Peyer's patches of the guinea-pig: a potential immunogeneic route. Colloidal carbon injected intravascularly provided a selective marker for post-capillary venules in lymph nodes and Peyer's patches. In the first few minutes a denticulate outline to the lumen was formed by carbon capping the high columnar epithelium and carbon particles were deeply embedded between endothelial cells. Ten minutes after injection carbon had reached the basement membrane and was lying outside this membrane 30 min later, at first free but later engulfed inside macrophages. Carbon was retained in post-capillary venules for the duration of the experiment (8 h). Discontinuities were present in the basement membrane in about one-fifth of venules, and lymphocyte and macrophage penetrating the basement membrane are demonstrated. It is postulated that carbon penetrates the post-capillary venular wall by increased intraluminal hydrostatic pressure arising from contraction of muscles that surrounded the lymphoid tissue in the case of the gut, or skeletal muscle compressing lymph nodes against a bony surface in the axilla, groin or neck. Secondly, if carbon is a model for particulate antigens, then post-capillary venules provide a potential immunogenic route whereby antigens can reach lymphoid tissues from the circulation, as proposed by Burwell (1962) for transplantation antigens.


Repeated myocardial infarction in non-arteriosclerotic and arteriosclerotic Sprague-Dawley rats. Adult male Sprague--Dawley rats, with and without arteriosclerosis, were subjected to an isoprenaline-induced myocardial infarction. After 4 weeks' convalescence, the survivors were subjected to a second myocardial infarct. Animals free of arterial disease were able to survive only 2 infarcts, whereas those with preexisting arterial disease were able to endure a third and some a fourth infarct. Changes in serum enzymes (CPK, SGOT, SGPT and LDH), lipids (triglycerides, free fatty acids and cholesterol), glucose, BUN, and corticosterone manifested intensification or diminution of their characteristic response pattern with each subsequent episode of acute myocardial infarction and repair. Many animals died as a result of left ventricular aneurysm formation. Animals with pre-existent coronary artery disease were especially capable of affecting repair of the myocardium or aneurysmal wall through mesenchymal or fibroblastic activity.


The detection of rubella-specific IgM antibodies by radioimmunoassay. An indirect solid-phase radioimmunoassay (RIA) has been developed for the detection of immunoglobulin (Ig) class-specific rubella antibodies. A commercial rubella haemagglutinin is dried and fixed on to the wells of flexible microtitre plates and allowed to react with serial dilutions of whole or fractionated human sera. Class-specific rubella antibodies are then detected by determining the specific binding of 125I-labelled anti-human IgG or IgM. The RIA was first evaluated by comparison with the haemagglutination-inhibition (HI) test for the detection of rubella-specific IgM in gel-filtration fractions. RIA was found to be as specific as HI but 10-150 times more sensitive. Rubella-specific IgG antibodies did not interfere in specific IgM determinations by RIA and therefore the latter technique was applied to unfractionated sera. The results obtained indicate that RIA on unfractionated sera is a practical, sensitive and specific technique which could provide a reliable method for the diagnosis of rubella. The rubella-specific IgM titres obtained by RIA were not increased by the removal of IgG by pretreatment of sera with Staphylococcal Protein A.


Nucleic acid metabolism in the rat following short-term and prolonged ingestion of chrysotile asbestos or cigarette-smoke condensate. Rats which have ingested a natural diet containing chrysotile asbestos (50 mg/day) both in the short (one week) and long term (5-15 months) show a statistically significant increase in the incorporation of [3H]-thymidine into DNA in the small intestine mucosa, colon and rectum, stomach and spleen and a significant decrease in the incorporation of this radiolabel into liver DNA. However, short-term ingestion of similar quantities of chrysotile produced no significant change in the incorporation of [3H]-uridine into RNA in any tissues, although prolonged ingestion of the mineral induced alterations in RNA metabolism in the lung and liver. By contrast, animals ingesting a natural diet containing cigarette-smoke condensate show a significantly high incorporation of [3H]-uridine into RNA in the mucosa, submucosa, spleen and heart following short-term exposure. Long-term ingestion of this diet produces similar changes in the submucosa, spleen and lung. The apparent specificity and the mechanism whereby ingested chrysotile interferes with DNA metabolism in some body tissues is discussed.


Rat alpha 1-acid glycoprotein: uptake by inflammatory and tumour tissues. The tissue distribution of intravenously administered 125 I-alpha 1-acid glycoprotein and 125I-albumin was studied in rats with inflammatory granuloma or transplanted sarcoma. The marked concentration of alpha 1-acid glycoprotein in extra-vascular spaces of the granuloma or sarcoma tissue was observed, most of which remained in a trichloroacetic-acid-precipitable form throughout the experiments. Albeit less marked, albumin also preferentially accumulated in both pathological tissues and presented essentially the same distribution pattern as alpha 1-acid glycoprotein in intact organs except kidney in both morbid states. The results suggest that serum alpha 1-acid glycoprotein might play an important role in inflammatory or cell proliferative processes in situ. The studies on trichloroacetic acid fractionation also indicate indicat a selective involvement of the kidney in the catabolic processes of alpha 1-acid glycoprotein as compared to that of albumin.


Reduction in inflammatory response by prior injection of a different agent at the same site: an experimental study in the rat. Glycogen, producing a weak PMN response, and BHI/PP, which induces a strong response, have been injected both separately and sequentially into the peritoneal cavity of the rat. It was found that the first stimulus, glycogen, had a modifying effect on the response to the second stimulus, which was reduced. Changes in the number of PMNs in the peritoneal cavity were found to correspond to PMN count changes in the blood, which were monitored simultaneously. This suggests the possibility that the number of PMNs in an exudate is dependent on blood PMN numbers. The point at which the modifying mechanism has its effect remains to be demonstrated, and an assessment of the importance of the changes in blood counts is crucial in locating the point at which the two stimuli interact.


Effect of antibody avidity on the induction of renal injury in anti-glomerular basement membrane nephritis. Antibodies to glomerular basement membrane (GBM) of the rat could be fractionated according to their avidity by elution from trypsin-digested GBM (bound to Sepharose) with increasing concentrations of KSCN. The percentage of kidney-fixing antibody in each fraction and the degree of proteinuria induced as determined 24 h after injection increased with the avidity of the antibody fraction when equal doses were administered.


Effect of stimulus repetition on negative sustained potentials elicited by auditory and visual stimuli in the human EEG. Effect of repetition of auditory and visual stimuli on sensory-evoked sustained potentials was studied. The stimuli were tones and flashes of 1 sec duration presented in trains of six stimuli with an inter-stimulus-interval of 1 sec. The repetition rate of the trains was 1 train/min. The EEG was recorded from electrodes located at Cz, Pz and Oz. Both auditory and visual stimuli elicited negative sustained potentials which during the first stimuli of the trains were maximal in amplitude and shortest in latency at Cz. Repetition of the stimulus resulted in almost complete disappearance of the sustained potentials; for auditory stimulation a small negative shift was recorded only at Cz, whereas for visual stimulation a small sustained potential was seen only at Pz and Oz. The results indicate that the slow potentials evoked by short tones or lights are composed of at least two components. One of these components may reflect neural processing associated with orienting reflex. The other component seems to be related to specific neural processing of the stimulus.


Habituation of the orienting response as a function of arousal induced by three different tasks. In order to investigate the extent to which habituation rate is influenced by the level of arousal, three consecutive experiments with 24 subjects each were carried out, involving the manipulation of arousal by a different task in every experiment. In Experiment I this was done  by pressing a dynamometer; in Experiment II by remembering words; and in Experiment III by the instruction to react as quickly as possible to barely noticeable stimuli, which in fact were not presented. Although in all experiments arousal was clearly increased, at least as measured by the number of spontaneous electrodermal responses (EDR) and as indicated by the level of either skin conductance, or heart rate or pulse volume, habituation of the EDR was delayed only in Experiment III. Experiment I however showed a faster habituation rate, at least of the EEG and pulse volume reactions. The results of Experiment III were replicated in Experiment IV with 27 subjects. It was concluded that habituation is not a function of arousal but possibly of a variable criterion for the 'signal value' of the stimulus.


Effects of physical activity on initial level and response magnitude: an experimental study of the LIV. Two exercise and two relaxation conditions were used to manipulate subjects' overall level of physical activity. A digit-transformation-and-recall task was administered under each of these four conditions in order to elicit physiological responses. Measures of prestimulus level and response magnitude were taken for each of six dependent variables: skin conductance (SC), heart rate (HR), finger pulse volume (PV), and three respiration indices. It was hypothesized that as the subject's degree of activity increased the physiological variables would show ergotropic changes in prestimulus level together with decreasing magnitudes of response to the digit task. The results provided a reasonable degree of support for these predictions. Evidence for concomitant changes in prestimulus level and response magnitude was consistent with Wilder's Law of Intial Value (LIV). There were some cases, however, where response magnitude showed a predicted effect of treatment in the absence of a difference in prestimulus level; these findings could not be explained by the traditional LIV model.


EEG event-related potentials and signal detection. The purpose of this study was to determine whether certain previously reported relationships between event-related potentials and measures of signal detection performance occur in vigilance as well as psychophysical settings. In the course of the study, evidence was found which challenges previously proposed psychological correlates of "P300". EEG was recorded while 15 subjects carried out a 40-min signal detection test. CNV was measured between a warning click and the brief offset of a dim light denoting the possible (p = 0.5) occurrence of the signal, a faint tone in the constant background noise. P300 was measured at a point 300 msec following offset of the dim light. As reported previously in psychophysical settings, P300 amplitude was positively related to signal intensity and response confidence, and was larger for correct detections (Hits) than for correct rejections, misses or false alarms. From first to second half of the test both Hits and false alarms fell, response criterion beta rose, and the amplitude of both CNV and P300 fell. The latter negative relationship between beta and P300 contrasted with a positive one when subjects rated their signal reports at three levels of confidence; here the most confident ratings (high beta) were associated with the highest amplitude of P300. CNV reflected individual ability to sustain performance. Results are explained in terms of a two-factor version (Wilkinson, 1976) of the prior state/reactive change hypothesis (Karlin, 1970). It is suggested that time on task constitutes a prior state influence on P300, whereas other variables influence P300 by means of either reactive change or 'real' change in an endogenous P300 component.


The sleep of 'morning' and 'evening' types. A questionnaire developed by Ostberg to differentiate 'morning' types from 'evening' types was administered to 100 college students. The actual sleep behavior of the 11 extreme 'morning' types (larks) and the 10 extreme 'evening' types (owls) was monitored for two weeks with a sleep log and the Post-sleep Inventory. Data was collected from the owls for a further two-week period in which the owls had been instructed to attempt to arise at the lark arousal time. In addition to going to bed earlier and getting up earlier than the owls, the larks had a less variable sleep length and awakening time and took shorter naps than the owls. Larks further reported fewer physical problems and less mental activity across the night as well as more adequate sleep than owls, who differed little from the normal college population even after having their awakening time shifted.


A review of the biological effects of total sleep deprivation in man. This biologically oriented review attempts to complement earlier and more psychological performance based  reviews of total sleep deprivation. Also, the effects of total sleep deprivation are interpreted, here, from a function of human sleep perspective, rather than from the more usual stress viewpoint. It would appear that total sleep deprivation does not produce any major changes in biochemical and physiological measures of somatic functioning. Such a conclusion would not seem to support an hypothesis that human sleep is for body restitution. Although there are equivocal results amongst several of the more psychophysiological measures, EEG does show a pronounced change. This latter finding, together with many reports of psychological performance detriment, would appear to sustain a CNS or cerebral restitutional role for human sleep. However, before definitive conclusions can be drawn from the biochemical and physiological findings of total sleep deprivation, the following qualifications of experimental methodology are made: (1) Apart from sleep loss, many studies have provided unnatural regimes which may have ameliorated possible effects of total sleep deprivation. (2) Most studies are of relatively short duration and may not have been sufficiently long for effects to develop. (3) Measures are often limited in range and depth of analysis. (4) Subjects are mostly fit, young adult, intelligent males and there is little constitutional variability. (5) Reported changes of statistical significance may be of no physiological significance and changes of possible physiological significance may be obscured by statistical procedures. (6) Intervening behavioural variables, such as novelty and anticipation of the sleep deprivation situation, may confound real effects.


Function of fever in infectious disease. The survival of fever in infectious disease is a controversial subject. In favour of the hypothesis that the fever response is one of the defence mechanisms of the host aginst micro-organisms are several data ranging from determinations of optimal growth temperatures of micro-organisms in vitro to in vivo experiments on the course of infections in temperature-manipulated warm-blooded and poikilothermic animals. In spite of this, the beneficial effect of an elevated body temperature has only been documented in a few human infections, and antipyretic drugs are still used in enormous quantities in the fight against the symptom "fever", as if this were the enemy.


The action of vitamin B1 (thiamine) on the cardiovascular system of the cat. Vitamin B1 administered in a high dose (160 mg/kg) parenterally is known to cause neuromuscular and ganglionic blockade. The effects on the cardiovascular system however have not been sufficiently investigated. In artificially ventilated cats under light ethrane-anesthesia, following parameters were measured continuously before and after B1 administration : Left ventricular pressure, left ventricular end-diastolic pressure, LV dP/dt max, electrocardiogram, heart rate, central venous pressure, and peripheral blood pressure (systolic, diastolic, mean). The data indicate a three-phase reaction after B1 injection : Phase 1--shortly after injection there is a drop of all parameters lasting for 30 sec. The LVEDP showed no change while CVP increased. The drop could not be eliminated by the pretreatment with antihistaminiergic or anticholinergic drug. Sequential stimulation with norepinephrine was able to re-establish base-line values. In Phase 2 (two minutes after injection) all parameters return to their control values ; except CVP which stays elevated. Phase 3 (around the 7th minute after injection) shows a gradual decrease of all parameters; CVP returns to control values. It is suggested that phase 1 represents an immediate alpha-blockade, phase 2 reveals a compensatory reflex mechanism, and phase 3 shows full ganglionic blockade.


Thymidine-suicide of human granulocytic progenitor cells (CFU-C). The quantitative and qualitative changes of human granulopoietic stem cells (CFU-C) after perturbation give a comprehensive view of their reaction pattern. The proliferative state of CFU-C may be assessed using the 3H-Thymidine (3H-TdR) technique. This technique is well established in experimental animals. In order to utilize it for the study of human CFU-C, the kinetics and the variables affecting the suicide of human CFU-C were analysed in detail. From the results, it appears that under optimal conditions considerable higher 3H-TdR concentrations (greater than or equal to 100/muCi/ml) have to be utilized than have been reported to be satisfactory in the murine system. Colony growth inhibition is S-phase-specific; if reutilization of the label occurs in vitro, it does not detectably affect colony growth. Minimum exposure of CFU-C to 3H-TdR is 20 minutes. Using these optimal suicide conditions, human marrow CFU-C can be shown to be a highly proliferating cell population.


Effects of hyperthermia and drug in cultured mammalian cells. Hyperthermia (42 degrees C) and peptichemio (PTC) applied simultaneously result in an increased killing effect and in a significant induction of single strand breaks (SSB) of DNA molecule. The enhanced killing effect was observed in all circumstances, whenever hyperthermia was applied before, during or after PTC treatment, but the most effective cell killing was obtained when hyperthermia and PTC were applied simultaneously. The results show that PTC concentrations used in these experiments do not induce SSB in DNA molecule during incubation for 2 hours at 37 degrees C. When the cells were exposed to PTC and hyperthermia the induction of SSB was observed. The number of SSB depends on the exposure time and PTC concentration. Cells with a greater number of SSB lost the capacity for repair during post-incubation at 42 degrees C.


Lymphokine and synthesis of complement by guinea pig spleen cells. Lymphokine preparations have been obtained from normal guinea pig spleen cells stimulated in vitro by optimal doses of insoluble Concanavalin A. The biological activity of these preparations was estimated by Macrophage Inhibition Tests performed with peritoneal cells from identical guinea pigs. Addition of these preparations to culture of normal adherent guinea pig spleen cells, gives rise to a dose related inhibition of the normal synthesis of C2, the second component of the complement system, by these latter cells. This inhibition of synthesis, appears to be due to a functional effect of lymphokine on C2-producing cells and not to a cytotoxic effect. Preliminary results indicate that the same lymphokine preparations can have a stimulatory rather than an inhibitory effect on synthesis of haemolytic C1 by the same cells.


Effect of high dose d-l propranolol on the renin-angiotensin system in glycerol induced acute renal failure in rat. Stimulation of the renin-angiotensin system has been implicated in the pathogenesis of post-ischemic and nephrotoxic acute renal failure. This study was designed to determine the effect of d-l propranolol in glycerol induced acute renal failure in rats. 50% glycerol administered alone, induced a significant rise in blood urea and plasma renin concentration but no significant change in renal renin concentration. When administered with d-l propranolol (10 mg/kg body weight in 5 subcutaneous injections), mean blood urea, plasma renin and renal renin concentrations were not significantly different from the preceding group. Propranolol alone, administered in the same fashion, unexpectedly induced a rise in plasma renin concentration (p less than 0.05) while blood urea and renal renin concentrations were unchanged. Considering the unusually high dose of propranolol used, a second protocol was devised to compare the effects of d-l propranolol, in doses of 10 mg/kg and 1 mg/kg. Plasma renin concentration rose after high dose propranolol, but decreased, although not significantly, after administration of 1 mg/kg. Renal renin concentration was unchanged. High dose d-l propranolol, does not protect rats against glycerol induced acute renal failure. Contrarily to the usual 1 mg/kg dose, it was found surprisingly to increase renin release.


Dopamine excretion in benign pheochromocytoma. Dopamine excretion is reported in 27 patients with benign pheochromocytoma. In 21 patients the tumours were in the adrenal (one patient, bilateral), four were extra-adrenal, and two were assumed to be so since they were not found at laparotomy. Dopamine excretion was found to be higher in the patients with extra-adrenal tumours and in one patient--with bilateral pheochromocytoma. Slight increase of dopamine excretion was found in two of the remaining patients. These observations--indicate that while increased dopamine excretion may be present in patients with malignant pheochromocytoma it can be also increased in some patients with benign tumours.


Surface features of small thymocytes of rat: a freeze-fracture and scanning electron microscope study. The surface of small thymocytes of 6 day old rats has been examined by freeze-fracture and scanning electron microscopy. Various procedures were used to enrich the cell population and protect their surfaces. On the basis of morphological criteria, three types of small thymocytes: smooth thymocytes (79.5% of total cells), thymocytes characterized by the presence of ridge-like profiles (16.1%) and thymocytes displaying a moderate number of small microvilli (2.4%). From the results after stimulation with PHA and later separation, it is concluded that the first population corresponds to small cortical thymocytes, and the second to small medullary thymocytes.


The gene(s) controlling the synthesis of C1 esterase inhibitor is not linked to the genes of the HLA system and is not on the 6th chromosome. Certain genes of the complement system are carried by the 6th chromosome and are sometimes linked to particular genes of the HLA system. This study shows that in 15 patients suffering from hereditary angioneurotic oedema the gene(s) controlling the synthesis of C1 esterase inhibitor is not linked to the genes HLA-A or B and is not on the 6th chromosome.


Quantitation of berberine chloride in human urine by use of selected ion monitoring in the field desorption mode. A method is described for the microdetermination of berberine chloride in human urine by a field desorption mass spectrometry selected ion monitoring system using a deuterium labelled analogue of berberine chloride as an internal standard. Prior to the quantitation of berberine in human urine, the fundamental problems related to field desorption selected ion monitoring, such as quality of emitters, amounts of sample loading, and the programming rate of the emitter current, were statistically investigated in detail. Berberine chloride can be determined in a concentration of 10 ng ml-1 in human urine by the method described. The analytical results were compared with those from gas chromatography mass spectrometry selected ion monitoring in the chemical ionization mode suggesting that the reliability of field desorption selected ion monitoring may be almost equivalent to that of gas chromatography chemical ionization selected ion monitoring.


[OH]- negative chemical ionization mass spectrometry. Reactions of [OH]- with methadone, l-alpha-acetylmethadol and their metabolites. The [OH]- chemical ionization spectra of methadone and three metabolites and of l-alpha-methadol and six metabolites are presented. The spectra are simple, but the methadol compounds exhibit much fragmentation. The ionization sensitivity is somewhat greater than that in CH4 positive chemical ionization.


Determination of choline and acetylcholine in distinct rat brain regions by stable isotope dilution and field desorption mass spectrometry. The determination of choline and acetylcholine by field desorption mass spectrometry from rat brain tissue samples has been demonstrated. Essential points of the assay are the use of stable isotope labelled internal standards, a simple ion pair extraction procedure, direct analysis of the quaternary ammonium ions without derivatization, and accumulation of the electrically recorded field desorption ion signals with a multi-channel analyser. The analysis of sample amounts in the picogram range gave quantitative data of good precision (0.6--10% standard deviation).


The identification of ibuprofen and analogues in urine by pyrolysis gas chromatography mass spectrometry. The pyrolysis gas chromatography mass spectrometry of Ibuprofen, Fenoprofen, Naproxen and Ketoprofen, a series of anti-inflammatory propionic acid derivatives, is shown to proceed via decarboxylation and elimination to yield characteristic ethyl and vinyl fragments. The pyrogram enables the identification of the drug to be achieved as the pure compound, in a formulated dosage form or excreted in urine. The presence of metabolites derived from Ibuprofen causes four new fragments to be observed in the urine pyrogram. The identification of 16 components of the control urine pyrogram is presented.


Mass spectrometric determination of cocaine and its biologically active metabolite, norcocaine, in human urine. A gas chromatographic mass spectrometric assay has been developed for the determination of cocaine and its pharmacologically active metabolite, norcocaine, in human urine. [2H3]Cocaine and [2H3]norcocaine were used as internal standards. The assay utilizes selective focusing to monitor in a gas chromatographic effluent the molecular ions of cocaine, [2H3]cocaine and the fragment ions of trifluoroacetylated norcocaine, [2H3]norcocaine generated by electron impact ionization. The assay can measure 2 ng ml-1 each of cocaine and norcocaine with about 5% precision. The curves, relating the amounts of cocaine and norcocaine added to control urine per 'fixed' amounts of their labeled analogs, versus the appropriate ion intensity ratios are straight lines with nearly zero intercepts and slopes of 0.98 +/- 0.01 and 0.98 +/- 0.02, respectively. The methodology is used for the analysis of urinary cocaine and norcocaine from three human subjects who received 100 mg cocaine-HCL intravenously.


Mass spectra of the oxygenated products generated from phenanthrene under simulated environmental conditions. The photooxidation of phenanthrene under stimulated environmental conditions to 9,10-epoxy-9,10-dihydrophenanthrene, among other oxygenated products, serves as a model for the conversion of polycyclic aromatic hydrocarbons to potentially mutagenic and/or carcinogenic products. The separation and identification were achieved by glass capillary gas chromatography mass spectrometry, and by comparison of gas chromatographic retention times and mass spectral fragmentation patterns with data observed for authentic samples obtained independently through synthesis or from commercial sources. The structural rearrangements of 2,2'-di-substituted biphenyls such as 2-formyl biphenyl-2'-carboxylic acid, 2,2' diformyl biphenyl and diphenic acid anhydride, induced upon electron impact are investigated and discussed in detail. The mass spectral comparison of 9,10-epoxy-9,10-dihydrophenanthrene, a primary mammalian metabolite of phenanthrene, and certain other structural isomers was conducted and the results of this study suggest a mass spectral technique capable of differentiating arene oxides from oxepin, phenol and carbonyl isomers. A discussion of the potential impact of the sensitized photooxidation of more condensed environmental polycyclic aromatic hydrocarbon pollutants is presented and the role of bioactive arene oxides produced under such photooxidation conditions is also discussed. Related oxides of polycyclic aromatic hydrocarbons are known to be proximate carcinogens and/or mutagens generated by metabolic activation. The role and significance of solar induced oxidation in the weathering of petroleum hydrocarbons at air-sea interfaces and the incorporation of potentially bioactive organic residues in the food chain are also addressed.


Identification of 4,6-O-(1-carboxyethylidene)-D-galactose by combined gas chromatography mass spectrometry. Combined gas chromatography mass spectrometry was used to separate and identify a carrageenan component suspected of being the acid ketal 4,6-O-(1-carboxyethylidene)-D-galactose. The mass spectral fragmentation pattern is presented as evidence of the presence of this component in the carrageenan from Petrocelis middendorfii (P. franciscana).


Mass spectroscopy of natural products. III--Mass spectrometric comparison of lysergic acid and 9,10-dihydrolysergic acid. The influence of the 9,10-double bond in the ergoline skeleton on the fragmentation behaviour of lysergic acid and 9,10-dihydrolysergic acid is discussed. The main fragmentation pathways were determined using high resolution mass spectrometry and metastable ion studies. The 70 eV electron impact spectra are compared with the 12 eV electron impact spectra and the negative ion mass spectra (2--4 eV).


A selected ion monitoring method for glutethimide and six metabolites: application to blood and urine from humans intoxicated with glutethimide. A method employing selected ion monitoring for the analysis of glutethimide and six of its metabolites has been developed. Hydroxylated metabolites analyzed as trifluoroacetates, included 4-hydroxyglutethimide, (1-hydroxyethyl)glutethimide and p-hydroxyglutethimide. The unchanged drug, 3-dehydroglutethimide, desethylglutethimide and the internal standard, [2H5]glutethimide, were chromatographed underivatized on OV-225. The assay was used to measure drug and metabolites in the plasma and urine of patients intoxicated with glutethimide. High levels (e.g. 20--35 microgram ml-1) of unconjugated 4-hydroxyglutethimide, an active metabolite, were found in all patients at a time when levels of unchanged drug were lower and declining. Other unconjugated and conjugated metabolites were found in relatively low concentrations in the plasma (i.e. less than 4 microgram ml-1). The major urinary metabolites were conjugates of 4-hydroxyglutethimide and (1-hydroxyethyl)glutethimide. The unchanged drug and other conjugated and unconjugated metabolites were found in lower amounts in the urine. Normal plasma half-lives of glutethimide and the relatively small amounts in urine of unchanged drug and unconjugated metabolites indicated that drug elimination was not markedly impaired in the intoxicated patients.


Quantitative analysis of propranolol and metabolites by a gas chromatograph mass spectrometer computer technique. A quantitative assay for urinary propranolol and six of its unconjugated metabolites by a gas chromatography mass spectrometry computer system has been developed. Conjugated metabolites are also determined following enzyme hydrolysis. These compounds are separated from murine by Amberlite XAD-2 resin column chromatography and are converted to methyl esters and trifluoroacetyl derivatives. Each substance is quantitated from reconstructed ion chromatograms using a specific mass or sum of masses for each compound by comparing its area with that of an appropriate internal standard. The minimum detectable concentrations are in the range of 50--100 ng ml-1. The calibrations are linear from 0.10--15.0 microgram ml-1 with recoveries ranging from 62--91%. This procedure yields a high degree of specificity, selectivity and reproducibility, as demonstrated by the analyses of urine from dogs receiving single 40 mg doses of propranolol orally.


Determination of clonazepam and its amino and acetamido metaoblites in human plasma by combined gas chromatography chemical ionization mass spectrometry and selected ion monitoring. Our previously published gas chromatography chemical ionization mass spectrometry stable isotope dilution assay for clonazepam and its 7-amino metabolite in plasma has been modified to obtain more consistent recoveries of the amine metabolite and to permit the determination of the 7-acetamido metabolite of clonazepam. In addition, the manuscript describes the details of a method for a least squares analysis of the nonlinear standard curves associated with the use of certain stable isotope labeled analogs as internal standard.


A selective and sensitive assay for urinary metanephrine and normetanephrine using gas chromatography mass spectrometry with selected ion monitoring. Vapor phase methodology for quantitative analysis of urine for metanephrine and normetanephrine as the pentafluoropropionyl derivative is described. The use of selected ion monitoring provided sufficient sensitivity and selectivity that milliliter aliquots of urine required only a simple scheme of sample processing; preliminary purification consisted of percolation through a column of XAD-2 followed by solvent extraction. The sample extracts were converted to the pentafluoropropionyl derivatives and analyzed by gas chromatography mass spectrometry with selected ion monitoring. Quantitative analysis was based on alpha[2H2]-beta-[2H1]metanephrine and alpha-[2H2]-beta-[2H1]normetanephrine which were added to the urine sample at the outset. The calibration plots for metanephrine and normetanephrine were linear from 10 ng ml-1 to 2000 ng ml-1 of urine permitting the detection of metanephrine and normetanephrine levels throughout the normal range and well into the subnormal range. Examples of application of the methodology to clinical investigation are described. The overall reproducibility of the sample processing methodology and instrumentation was assessed by replicate analyses of the same urine sample over a period of several weeks; the coefficient of variation was +/- 2.5% (n = 8).


Erythroid colony production in vitro as a function of exposure time to erythropoietin. The effects of timed exposure to erythropoietin of murine bone marrow cells has been studied in in vitro plasma clot cultures. Erythropoietin was added at the start of the incubation period, and at various times after initiation of the culture an anti-erythropoietin serum was added in an amount adequate to neutralize the erythropoietin. Culture methods were used which allow the transformation of the immediate progenitor stem cell of the recognized erythron, the CFU-E. The incorporation of 59Fe was used as an identity marker for hemoglobin synthesis which allowed the classification of colonies as erythroid in autoradiographs. Brief exposure to the hormone for one to two hours produced activation of about 20% of the control (continuous exposure for the 48 h of culture) value. More protracted exposure to erythropoietin caused the conversion of what appears to be a second population of CFU-E, but even 24 h of exposure was not adequate to cause the maximum activation of CFU-E seen in the control cultures.


Erythropoiesis: comparison of in vivo and in vitro amplification. 1. Amplification is defined as the phase of erythropoiesis that includes all cell divisions of the recognizable erythron. 2. In vivo, amplification always takes place surrounding a central histiocyte (erythroblastic island). It is made up of four to five successive synchronous divisions. 3. In vitro, complete maturation and amplification of erythropoietic cells can be obtained without apparent association with a central histiocyte. 4. The functional significance of the 'erythroblastic island' and disorders of amplification are discussed in relation to clinical disorders of erythropoiesis.


Congenital hypoplastic anemia: Diamond-Blackfan syndrome. Historical and clinical aspects. A summary of the historical developments associated with congenital anemias are discussed. The clinical status, the peripheral blood and bone marrow picture of these patients are reviewed. The effectiveness of treatment and prognosis for these patients is evaluated.


Beta thalassemia with reticulocytopenia: clinical, biochemical, and ultrastructural studies. An unusual form of beta thalassemia is described in two children of unrelated families. Its main features are a severe anaemia with a low reticulocyte count associated with an erythroblastic hyperplasia; these characteristics indicate a completely ineffective erythropoiesis. The results of the study of haemoglobin synthesis performed on the bone marrow in vitro showed a greater imbalance in chain synthesis than that typically found in Cooley's anaemia. Ultrastructural studies revealed, in erythroblasts, all the features observed in Cooley's anaemia, although these features were more widely encountered. In addition, two peculiar findings were noted: (1) many inclusion bodies, which were partially or totally surrounded by smooth membranes, and which may indicate an autophagic phenomenon; and (2) a spongy appearance of the chromatin in rare erythroblasts of one of the two patients which resembled that found in congenital dyserythropoietic anaemia type I. These findings suggest that the great imbalance in the synthesis of the haemoglobin chain is responsible for the presence of an increased number of inclusion bodies and results in the death of nearly all the late erythroblasts. Furthermore, the present results point out the need for further study of the synthesis of the globin chains in atypical congenital dyserythropoietic anaemias.


Surface features and ultrastructure of isolated Kupffer cells as seen by scanning and transmission electron microscopy. The present report describes ultrastructural and surface features of hepatic Kupffer cells, with particular emphasis on the characteristics of these cells in suspension, as seen under the scanning electron microscopy (SEM), after their successful isolation by pronase digestion of liver tissue. Kupffer cells were readily recognized in sections of the liver examined by transmission electron microscopy, particularly after tagging by carbon, heat-damaged erythrocytes, and latex spheres. Their ultrastructural features in suspension and in liver sections were similar to those described for peritoneal macrophages. In the present study, a high yield of well-preserved Kupffer cells was obtained after selective enzymatic digestion of intact rat liver. Kupffer cells were readily distinguished from lymphocytes and hepatocytes on the basis of their surface architecture, and showed transverse ridge-like profiles and ruffled folds which became more prominent during phagocytosis. The sequence of events during the various stages of latex bead phagocytosis was well visualized with the SEM. Kupffer cells in suspension, during spreading and attachment to glass and during phagocytosis, resembled peritoneal macrophages isolated from rats, providing further evidence that these cell types are closely related.


Determination of red cell shape from random cross-sections. By a computer simulation the relative proportion of specified geometrical shapes produced by the sectioning of a mass of randomly-oriented red cells is determined. It is shown that the proportions obtained on the assumption that the cells are all of identical shape are the same as if they had come from a population of cells possessing the normally accepted spread of shapes. It is suggested that a sectioning technique based on the principles presented in this paper could form the basis of a relatively simple procedure for determining on a quantitative basis deviations of red cells from their normal shape.


On the proper use of the Soret band for hemoglobin detection in erythrocytic cells. Intracellular hemoglobin detection by light microscopy in the Soret band (414nm) is a sensitive means of correlating morphology and biochemical function in studies of erythrpoiesis. Correct application of the technique requires a light source with strong emission in the near ultra-violet, a filter with a pass-band at 414nm, a preparation of living cells or an unfixed smear, and a receiver that is sensitive to the Soret wavelength. The human eye is very insensitive to light at 414nm and quite sensitive to stray green light: it is consequently much inferior to a black and white television or camera film for viewing a Soret image. The appearance of hemoglobin during maturation of erythroid cells in human bone marrow can be detected with greater sensitivity by this method than by a peroxidase-benzidine stain and it is the only method applicable to living cells.


On the role of thymus in hemopoietic differentiation. This study was performed to investigate further the connection between the thymus and blood formation suggested by earlier findings. Bone marrow, after in vitro treatment with either anti-thy 1.2 (alpha Thy 1.2) or nonimmune serum and complement, was transplanted to two separate groups of lethally X-irradiated isogenic recipient mice of several different genotypes. Twelve studies were done, and macroscopic spleen-colony numbers were found to be similar in the two groups; however, differences were found when spleens were examined microscopically. The most striking and consistent finding was a decrease in granulopoietic colonies in recipients of alpha-Thy-1.2-treated marrow. There were less pronounced decreases in erythropoietic and in total colonies (all hemopoietic kinds). Ratios of erythropoietic to granulopoietic colonies were regularly increased. Anemia did not develop over a period of 4 months in chimeras given either kind of treated marrow.


The relationship between the spleen colony-forming cell and the haemopoietic stem cell. Several experimental findings that are inconsistent with the view that the spleen colony-forming cell (CFU-S) is the primary haemopoietic stem cell are reviewed. Recovery of CFU-S, both quantitatively and qualitatively, can proceed differently depending upon the cytotoxic agent or regime used to bring about the depletion. The virtual immortality of the stem cell population is at variance with evidence that the CFU-S population has an 'age-structure' which has been invoked by several workers to explain experimental and clinical observations. To account for these inconsistencies, a hypothesis is proposed in which the stem cell is seen in association with other cells which determine its behaviour. It becomes essentially a fixed tissue cell. Its maturation is prevented and, as a result, its continued proliferation as a stem cell is assured. Its progeny, unless they can occupy a similar stem cell 'niche', are first generation colony-forming cells, which proliferate and mature to acquire a high probability of differentiation, i.e., they have an age-structure. Some of the experimental situations reviewed are discussed in relation to the proposed hypothesis.


[Action of HCG on isolated and cultivated sow ovarian granulosa cells]. Granulosa cells harvested from cavitary follicles of varying diameters have been cultivated in vitro in basic conditions and in presence of HCG, and then tested for the activity of steroid-3 beta-ol-dehydrogenase and observed with a scanning electron microscope. As concerns the enzymatic activity, the cells of the smaller follicles (5--6 mm) show a very low reactivity which increases in presence of HCG. In the cells of the larger antral follicles (8--9 mm) the reactivity is remarkably higher, particularly when HCG is added to the medium. With the scanning electron microscope the appearance of the granulosa cells of the larger follicles cultivated with HCG is very peculiar because of the presence on the cell surface of many cytoplasmic evaginations. These are more numerous and thinner than those normally found on the uncultured cells and on the cells cultivated in basic conditions.


[Pigmentation of feather primordium achieved by grafting of retinal pigment epithelium]. Small fragments of the retinal pigmented epithelium from White Leghorn, Rhode Island Red chick embryos, and from Quail, Starling and Red Partridge embryos, were grafted into the wing bud of White Leghorn chick embryos. Retinal pigmented epithelium of White Leghorn chick embryos did not give rise to pigmentation of feather primordia in the hosts. In contrast, 60% of grafts from Rhode Island Red, Quail, Starling and Red Partridge, gave rise to feather primordia whose pigmentation was identical to that of the donors. Pigmentation depends on the fact that some graft retinal melanocytes diffuse in the wing bud of the host and reach the feather primordia. This was shown by the Feulgen technique in embryos grafted with Quail retinal pigmented epithelium, taking advantage of the fact that Quail cells possess DNA rich nucleoli. The local factors which allow the migration of the melanocytes are probably inactive on the retinal melanocytes of the White Leghorn chick embryos, whose genotype does not contain the "feather pigmentation" character.


[Action of testosterone on 5'nucleotidase activity in the rat epididymal epithelium]. The epididymal epithelium of the rat has a 5'nucleotidasic activity, which is located in the basal cells and in the apical border of the principal cells. After bilateral castration, the pattern of this enzymatic activity is modified, but it is restored by a testosterone treatment. Bilateral castration abolished the apical activity of the epithelium, while the basal cells remained active. However different migratory aspects of basal cells seem to show their participation in the secretory function of the epithelium. Testosterone thus appears as a regulator for the basal cells activity and this would explain its role in the epididymal function.


[Arterial vascularization of the temporomandibular joint]. Anatomical and radiological study of the arteries of the temporo-mandibular joint in 18 foetuses and 4 adults. Branches arising from the superficial temporal artery, from the anterior tympanic artery as well as from the deep posterior temporal artery are found in all cases. Branches arising from four other arteries did not occur regularly: those coming from the deep auricular artery, from the transverse facial artery, from the middle meningeal artery, or sometimes directly from the maxillary artery.


[Early histochemical aging of arteries submitted to constant physical stress]. The hemodynamic stress effect on the tissue metabolism of coronary and splenic arteries was histochemically and comparatively studied in beagle dogs 6 months, 1 and 8 years-old. The results indicated that more than 30 enzyme activities (EA) studied are similar in both vessels in the young animal (6 months). During ageing (1--8 years old dogs) the EA linked to aerobic oxydo-reduction, ATP hydrolysis and estero-lipolysis decreased in the coronary arterial wall; conjointly the lysosomal acid phosphatase increased. Splenic artery EA remained unchanged during this period. These data suggest that repeated hemodynamic injuries may accelerate aging of the coronary artery by early perturbations of EA linked to oxydoreduction and to lipolytic power of the arterial smooth muscle cells.


[Mammary carcinoma: prognosis value of intra-mammary spread (author's transl)]. At the conclusion of this study based on 327 cases of breast cancer T1, T2 T3 (less than 7 cm) No, N1, Mo Pev O, treated by mastectomy and axillary dissection without previous treatment, it appears that the microscopic dissemination to the nipple has a pejorative prognosis value. The 5 years is 84 p. 100 when there is no nipple dissemination, 74 p. 100 when there is an intraductal nipple dissemination, and 57 p. 100 when there is lymphatic or interstitial nipple dissemination. These differences have a statistical value. This value does not seem connected with other pathological prognosis factors: tumors size, Bloom histopronostic grading, and the number of nodes invaded. The intra-mammary spread without nipple involvment has no prognostical value.


[Human mammary carcinoma: relationship between steroid hormone receptors and histopathology. An hypothesis, the prognostic value of hormone receptors (author's transl)]. In 318 cases of human primary breast carcinoma, the presence and content of estrogen receptor (ER) have been correlated to histopathological features of these carcinomas. We have evidenced that: a) there is a relationship between the ER presence, the histoprognostic grade and the histological type; b) there is no correlation between the frequency of ER presence, the neoplasic cellularity and the stromal reaction. The presence of ER appears to be related to a differentiated state of the carcinoma and to a moderate neoplasic activity. These data show that ER, correlated with histopathological features, could be used as an estimation's factor of the cellular activity of a human mammary carcinoma, thus as a factor of better prognostic value for the evolution of this tumor.


[Adenocarcinomas of unknown origin. Study of 17 autopsies (author's transl)]. This article reports on the autopsy results of 17 patients with adenocarcinomas from occult primary tumours: 10 are of bronchial origin, 3 of renal origin, 1 of hepatic origin, 1 of ovarian origin, and 1 of pancreatic or bronchial origin. In one case no primary tumour was found. Factors which can lead the clinicians toward further investigations are the location or nature of the first clinical signs (neurological and respiratory for bronchial cancers, subdiaphragmatic for primary abdominal tumours) and smoking habit (bronchial carcinoma in smokers).


[Anticancer chemotherapy: practical management and medical coordination (author's transl)]. The authors have studied the conditions of application of a protocol of palliative chemotherapy in breast cancers for the first 100 patients undergoing this protocol. The overall management of the treatment has been satisfactory. The medical team from the cancer center has directed the treatments; however, their participation, although substantial has been limited. The participation of other doctors, especially general practitioners, has been important and of good quality. The coordination between the various doctors has been almost always satisfactory. The authors stress the positive aspects of this study: the protocol has been respected in the majority of the cases; the duties have been well distributed among the various participating doctors; good medical cooperation leaves only a few minor details which could be improved. These results encourage the continuation of an approach whereby the general practitioner participates fully with the oncologic team in patient management and cancer control.


[Psychological factors in the etiology of cancers: methodological problems (author's transl)]. There is a multiplicity of etiological factors in human cancer; psychic factors are probably neither the most important nor the most constant. Nonetheless, owing to the potential infinity of psychological variables, it is necessary to formulate hypotheses in an operational manner. The casuistic method allows a thorough clinical study of objective events, of the manner in which the patient lives them and, especially, of what they mean to him. Such an approach, however, has shortcomings which must be accepted: it cannot administer proof of the hypotheses it advances. The superiority of prospective methods over retrospective methods seems indisputable for there is no evidence that personality traits are not modified by the fatal threat of a serious illness. This criticism also holds for the modified retrospective methods, the so-called predictive methods. Research focussed on particular cancers with a study of limited psychological variables seems desirable.


Similarity in morphological appearance of cycling and resting hemopoietic stem cells. The morphological entity which has been identified previously as the most likely candidate for the pluripotential hemopoietic stem cell in mouse bone marrow, has been encountered in HSC concentrates of rat bone marrow. An identical correlation between percentage of HSC identified in electron microscopical preparations and percentages HSC calculated from results of spleen colony assays has been observed for HSC concentrates from normal rat marrow and from rat marrow in which the CFU-s had been induced into the cycling state by in vivo pretreatment with hydroxyurea. The ratio between counted HSC and calculated HSC was 0.5 in both cases and a similar ratio was calculated from previous experiments with mouse bone marrow. Evidence is provided that the deviation of this ratio from the expected value of 1 is not due to the use of erroneous f factors. This discrepancy can be explained by postulating a heterogeneity of spleen colony forming cells, in the sense that only 50 per cent of spleen colonies originates from pluripotential HSC and that the remainder arises from committed stem cells which have a different as yet not identified morphological appearance.


S-phase fractions of breast carcinomas. Relationships to morphology, estrogen and progesterone receptors, and early recurrence. Analysis of the S-phase fractions (SPF) measured by in vitro thymidine labeling, morphological appearances, and estrogen receptor (ER) assays of primary invasive breast carcinomas demonstrated several interrelationships. Lobular, mucinous, tubular, and adenocystic carcinomas consistently had low SPF and were usually positive for ER. The same was true for the carcinomas of no special histologic type [the not otherwise specified (NOS) group of E. R. Fisher including "infiltrating ductal" and undifferentiated carcinomas] with minimal anaplasia. Medullary, atypical medullary, and morphologically unclassifiable carcinomas with marked nuclear anaplasia nearly always had high SPF and were usually negative for ER. High SPF was associated with advanced stages of carcinoma initially or with early recurrence following mastectomy.


Effect of starvation on survival of three bacterial isolates from an arctic soil. Three isolates, a Pseudomonas sp., a Bacillus sp. and an Arthrobacter sp., which had been isolated from a meadow soil at Devon Island, Canada, were subjected to starvation under varying conditions. The viabilities of the three isolates during starvation for 30 days in a carbon-free medium was assessed after the organisms had been grown continuously at varying rates in carbon- and nitrogen-limited media at 5 and 15 degrees C. Pseudomonas M216 was the most resistant to starvation stress, Bacillus M153 the least, and Arthrobacter M51 was intermediate in its response. Cells grown and starved at 5 degrees C survived longer than those at 15 degrees C. Carbon-limited Bacillus and Arthrobacter cells grown at high rates prior to starvation survived longer than those grown slowly, while in nitrogen-limited Arthrobacter the reverse was observed. The pattern of endogenous metabolism of the three isolates during starvation at 15 degrees C for 10 days was similar to that observed in other organisms. Levels of endogenous substrates such as carbohydrate and protein showed a rapid decrease in the initial 20 h of starvation, followed by a gradual decline over the remainder of the starvation period. The rates of endogenous metabolism of the isolates were positively correlated with their survival rates during starvation.


Effect of freezing and thawing on survival of three bacterial isolates from an arctic soil. Three isolates, a Pseudomonas sp., Bacillus sp., and Arthrobacter sp., which had been isolated from a meadow soil at Devon Island, Canada, were subjected to freezing and thawing at low rates under various conditions. When cells were frozen in sand or soil, survival was dependent on moisture level, storage time, and thaw rate. Pseudomonas M216 was most susceptible to freeze-thaw damage under these conditions. Arthrobacter M51 was the most resistant of the three isolates when frozen in sand or soil and when frozen at a high rate after growth at varing rates at 5 and 15 degrees C in carbon-or nitrogen-limited media. Pseudomonas M216 was more sensitive to freeze-thaw damage when NaCl was present in the freezing menstruum, even at low freezing rates. Survival of cells frozen in growth medium, water, saline, and soil extract was not affected by the freezing rate when it was less than 1 degrees C min-1. Soil extract did not protect cells from freeze-thaw damage any more than water and for Arthrobacter M51 survival was decreased when it was frozen in soil extract.


Spore germination, colony development, and secondary metabolism in Penicillium brevicompactum: a radiogas chromatographic and morphological study. A study of the first 76 h of development of spores of Penicillium brevicompactum in batch-mode shake culture indicates that mycophenolic acid biosynthesis begins when the hyphae of germinating spores aggregate to form pellets. Supplies of mycophenolic acid so produced augment a pre-existing pool of the material that is associated with the dormant spore. Although acetate metabolism is active at all stages of development, incorporation of [1-(14)C]acetate into 2,4-dihydroxy-6-(1',2'-dioxopropyl)benzoic acid, another secondary metabolite of the fungus, could not be demonstrated. The significance of these data are considered in terms of the function of mycophenolic acid and the substituted benzoic acid in the producing organism.


Apparent replication of an unusual virus-like particle in both a parasitoid wasp and its host. Nuclear inclusion bodies are found in the hemocytes of all tussock moth larvae parasitized by the braconid wasp Apanteles melanoscelus. These inclusion bodies represent the apparent site of replication of an unusual virus-like particle. Identical particles are observed in the nuclei of a small number of parasitoid calyx cells and are probably transmitted to host larvae during oviposition.


Characterization of the bacterial flora associated with root systems of Pinus contorta var. latifolia. Root systems of young and mature lodgepole pine (Pinus contorta Dougl. var. latifolia Englem.) were removed from forest stands and the associated aerobic bacterial flora isolated. Characterization of rhizoplane and control soil isolates from these tree root systems demonstrated differences from that reported for agricultural crops. Ammonifying, proteolytic, and amylolytic organisms were proportionately reduced within the rhizoplane. The rhizoplane organisms grew more slowly than the control soil isolates, although they responded in greater numbers to the addition of an amino acid supplement to the growth media. The rhizoplane organisms also showed an increased ability to solubilize phosphate. The chitinolytic organisms were suppressed within the rhizoplane of the mature tree but were stimulated by the young trees. With this exception, the rhizoplane microflora of older and younger trees were similar.


Rhizobium strain identification in Arachis hypogaea nodules by enzyme-linked immunosorbent assay (ELISA). The technique of enzyme-linked immunosorbent assay (ELISA) was used for serological identification of peanut Rhizobium strains both in cell suspension of pure culture and in single root nodules of groundnut (Arachis hypogaea) plants. Antisera of three peanut Rhizobium strains were tested against eight different Rhizobium isolates. Three serogroups identified by agglutination and immunodiffusion tests were confirmed by ELISA. In this experiment ELISA was more sensitive by four to six orders of magnitude than the agglutination and immunodiffusion tests and enabled the detection of Rhizobium antigens in cell suspensions of 10(4)-10(5) cells per millilitre. The reactions of culture and nodule antigens were identical for all strains investigated. ELISA enabled the precise typing of rhizobial isolates in single small root nodules. The minimum fresh weight of nodule tissue necessary to perform the ELISA test was 0.4 mg crushed in 1 ml of phosphate-buffered saline (PBS). ELISA was also successfully used for strain identification in mixed inoculated plants. One of the strains in each pair formed most of the nodules examined.


Oxidation of formate by mycobacteria of the scrofulaceum group. Intact cells obtained from Mycobacterium scrofulaceum as well as from mycobacterial strains M.A6 and M.R56 isolated respectively from leprous tissues of armadillo and rat leproma and grown with glycerol as the oxidizable substrate catalyzed complete oxidation of formate. The stoichiometry of formate oxidase system yielded a value of 2 mol of CO2 produced per mole of O2 or per 2 moles of formate consumed. Cell-free preparations from these three strains of mycobacteria contained formate dehydrogenase which was associated exclusively in the particulate fraction. Formate oxidation was markedly stimulated by small amounts of selenite and molybdate added together. Formate-reduced minus oxidized difference spectra disclosed cytochromes of the b type while spectral evidence did not suggest the existence of cytochromes a or c components. The effect of 2-N-heptyl-4-hydroxyquinoline-N-oxide on the redox state of cytochromes indicated that formate oxidation was mediated by cytochrome b with absorption maximum of 556 nm and not of 562 nm.


A rapid fluorescent focus-inhibition test for determining dengue neutralizing antibody and for identifying prototype dengue viruses. Neutralizing antibody to dengue virus in human and animal sera was assayed by the rapid fluorescent focus-inhibition test (RFFIT). Neutralizing-antibody titers could be detected after only 24 h compared to 5--6 days required by the plaque-reduction test. The RFFIT is more definitive than the conventional complement fixation (CF) or hemagglutination-inhibition (HI) test in identifying prototype dengue viruses, is reproducible, and is applicable to the routine detection of neutralizing antibodies to dengue viruses.


Isolation and partial characterization of the parasporal body of Bacillus popilliae. The sporangial wall of Bacillus popilliae encloses a spore and parasporal body and is very resistant to breakage. High-energy sonication can disrupt this envelope and release free spores and parasporal bodies which retain refractility. Parasporal bodies, free spores, and sporangial debris were separated by centrifugation in linear sucrose gradients. Purified parasporal bodies are proteinaceous. Of the 17 amino acids detected, glutamic and aspartic acids are highest in concentration and account for the low isoelectric point of 4.5; a lipid moiety was not found. Parasporal bodies are soluble in 0.1N NaOH, 8M guanidine hydrochloride, 8M urea, or alkaline thioglycollate. Paper electrophoresis at 3000 V separated soluble parasporal protein into three cathodic components. Solubilized or whole intact parasporal bodies fed to third-instar larvae of the Japanese beetle were not detectable toxic. However, solubilized parasporal protein was twice as toxic as the intact parasporal bodies when injected into the hemocoel.


Mode of action of bacteriophage phi 149 on cholera and El Tor vibrios. Bacteriophage phi 149 which was propagated in Vibrio cholerae (classical) OGAWA 154 strain, killed Vibrio cholerae (El Tor) strain MAK 757 without phage propagation. El Tor vibrios underwent a small degree of lysis only when infected by the phage phi 149 at a high multiplicity of infection and lost their viability at a rate-dependent multiplicity of phage infection. Evidence was obtained with 32P-labelled bacteriophage phi 149 for penetration of phage DNA into both bacterial strains. In host strain (OGAWA 154) phage particle synthesis occurred normally. In El Tor strain MAK 757 the phage DNA was not degraded but its expression was blocked. The killing effect of phi 149 on El Tor strain MAK 757 is supposed to be due to damage of the cytoplasmic membrane, which could not be repaired under the influence of phage information. This was indicated by a blockage of cellular respiration and RNA and protein synthesis.


Induction of transformation competence in Azotobacter vinelandii iron-limited cultures. Azotobacter vinelandii strains UW (Nif+) or UW1 (Nif-) were induced to form competent cells by growing cultures in Burk medium without added iron. Competent cells were generated in either liquid or solid medium. The competent culture was highly colored by the characteristic fluorescent green pigment of A. vinelandii but all pigmented cultures were not competent. In liquid culture, competent cells required a fixed nitrogen source (ammonia, nitrate, or urea) that was also a nitrogenase repressor. Glucose, sucrose, glycerol, and mannitol (1% w/v) were excellent C-sources for competence induction while acetate (1% w/v) and beta-hydroxybutyrate (0.2% w/v) were ineffective. Cells induced in liquid culture remained competent for a 12-h period before the end of the exponential growth phase, then competence decreased rapidly upon the initiation of the stationary phase of growth.


Mitogenic and protective activity associated with a lipopolysaccharide from Coxiella burnetii. A purified lipopolysaccharide (LPS) isolated from the rickettsial agent of Q fever, Coxiella burnetii phase 1, possesses some of the in vivo and in vitro biological properties previously only associated with bacterial endotoxins. The Coxiella LPS is mitogenic for guinea pig leukocytes, induces non-specific resistance in mice to virulent Candida albicans, causes dermal Schwartzman reactions, and is positive by the limulus lysate assay.


Isolation of auxotrophs of Bacteroides fragilis. Techniques employing ethane methanesulfonate and modified penicillin enrichment were developed whereby auxotrophs of Bacteroides fragilis could be readily isolated. Several auxotrophic phenotypes are described.


Non-toxic goitre: diagnostic role of aspiration cytology, antibodies and serum thyrotrophin. Fifty cases of bilateral non-toxic goitre, largely unselected, have been studied using fine needle aspiration cytology (without local anaesthesia); four techniques of thyroid antibody tests; serum thyroid biochemistry (including radioimmunoassay of TSH) and clinical evaluation. Autoimmune thyroiditis was found cytologically in 64%; simple colloid goitre in 24%; subacute thyroiditis of de Quervain in 10%. Aspiration cytology was the most sensitive means of detecting autoimmune thyroiditis and subacute thyroiditis. Two antibodies directed against the intra-cellular cytoplasmic antigen--the complement fixation test and an immunofluorescent antibody were of lesser value in detecting autoimmune thyroiditis (80% positivity) though equal to each other. Serum TSH was of some value--being elevated in 63% of cases of autoimmune thyroiditis and in no cases of simple colloid goitre. Two major cytological subtypes of autoimmune thyroiditis have been described--with significant differences in duration of goitre, mode of presentation, frequency of hypothyroidism, and response to thyroxine therapy. The high frequency of autoimmune thyroiditis in this series suggests that endemic goitre is unlikely in Western Australia.


The effect of serum ionized calcium elevation on somatostatin inhibition of glucose-induced insulin release in humans. The effect of somatostatin on the insulin response to an acute intravenous glucose load was studied in five normal subjects before and after induction hypercalcaemia. In the normocalcaemic state, the insulin response to glucose was depressed by somatostatin. In the hypercalcaemic state, insulin responses to glucose in the presence of somatostatin, were partially restored and appeared to be related to the level of increment of serum ionized calcium. It is concluded that, in the human being, hypercalcaemia and somatostatin have opposite actions on glucose-stimulated insulin secretion.


Increased serum oestrone and oestradiol following spironolactone administration in hypertensive men. The present study was undertaken to evaluate long-term effects of spironolactone on basal serum oestrone, oestradiol, testosterone, LH and prolactin concentrations in hypertensive male patients. Serum prolactin response to TRH was also evaluated. Patients were divided into two groups: a conventional-dosage group, consisting of six males with essential hypertension who took 75 to 150 mg of spironolactone daily for 12 weeks, and a high-dosage group, consisting of two males with idiopathic hyperaldosteronism who took 300 mg of spironolactone daily for more than 40 weeks. In the conventional-dosage group, serum oestrone concentrations significantly increased (P less than 0.01) at 12 weeks, serum oestradiol concentrations gradually increased throughout the study period, however, the increments were not statistically significant (P less than 0.2). Basal serum testosterone, LH and prolactin concentrations were not significantly changed throughout the study period. Enhancement of serum prolactin response to TRH was not found in any of the patients in the conventional-dosage group. In the high-dosage group, serum oestrone maintained high levels from the beginning of this study, and serum oestradiol concentrations increased with the development of gynaecomastia. Serum testosterone, LH and prolactin concentrations did not show any definite change throughout the study period. Thus, long-term spironolactone treatment increased the serum levels of oestrone and oestradiol in hypertensive men followed by the development of gynaecomastia. The elevation in circulating oestrogens could well explain the oestrogenic side-effects of spironolactone treatment.


Prolactin and luteal insufficiency.

Prolactin and luteal insufficiency. The relationship between mid-luteal plasma levels of progesterone and prolactin was studied in 75 women with regular menstrual cycles. Eighteen women had normal prolactin (mean 260 +/- 51.7 mU/l) and normal progesterone levels (mean 67 +/- 21.3 nmol/l). Thirty-nine women had elevated prolactin levels (mean 850 +/- 503 mU/l): progesterone levels were normal in all cases (mean 61 +/- 22.3 nmol/l). Eighteen women had evidence of luteal deficiency (mean progesterone 15.3 +/- 7.7 nmol/l); prolactin levels were normal in all cases (mean 243 +/- 106 mU/l). There was no correlation between plasma prolactin and progesterone levels.


Growth hormone modulation of arginine-induced glucagon release: studies of isolated growth hormone deficiency and acromegaly. Plasma glucagon and insulin responses to L-arginine were compared in normal controls and patients with isolated growth hormone deficiency and acromegaly. Patients with isolated growth hormone deficiency were characterized by high  plasma glucagon response and low plasma insulin response, whereas acromegalic patients showed exaggerated plasma glucagon response and almost normal insulin response. These results suggest that growth hormone is probably required for optimum function of the islets, and since hyperglucagonaemia was observed in both growth hormone deficiency and acromegaly, metabolic disturbances stemming from the respective primary diseases may affect glucagon secretion.


Stimulation by growth hormone of somatostatin release from the rat hypothalamus in vitro. Growth hormone (GH) has been shown to cause a dose-dependent increase in the release of immunoreactive somatostatin from the rat hypothalamus in vitro, thus providing further evidence that GH may be involved in a "short loop" feedback, controlling its own secretion via hypothalamic somatostatin release.


Medical toxicology: a primer for the medicolegal age. The medicolegal medical toxicologist is described: What they do, what toxicology is, how the toxicologist moves in a world of regulations, chemicals, differential diagnosis, and treatment of poisoning; his or her knowledge as an expert witness in evaluation of serious adverse drug reactions, medical malpractice, and poisoning cases; and the toxicologist's awareness of the role of alcohol, the problem of causation of death, and the limitations of the laboratory are discussed.


cis-Platinum ototoxicity.

cis-Platinum ototoxicity. The incidence and spectrum of ototoxicity secondary to cis-platinum administration in 104 cancer patients ranging in age from 8-78 years were determined. Pure tone thresholds from 500 to 8000 Hz were evaluated prior to and following cis-platinum administration. The most sensitive frequencies were 6000 and 8000 Hz. Younger patients had lower threshold increases per administered dose than older patients. High drug dosages caused larger threshold elevations and extended to lower frequencies. Prehydration and mannitol infusion did not alter ototoxicity. Audiographic evaluation appears necessary for monitoring the treatment of cancer patients with cis-platinum.


Severe neurotoxicity and lithium therapy. The patient, a manic depressive who was treated with lithium for three years, suddenly developed severe neurotoxicity and a glomerulonephritis-like syndrome. The author believes that the lithium toxicity was facilitated by hot weather with excessive sweating, gall bladder pathology with fever, and decreased water and salt intake. The patient improved except for a persistent hypertension. Propranolol not only improved the hypertension but alleviated a lithium-induced tremor as well.


Modification of cardiopressor and respirogenic effects of doxapram by propranolol. The respiratory stimulant doxapram hydrochloride has long been shunned in the United States because of a perpetuated fear of the alleged side effects of hypertension and tachycardia with attendant hypermetabolism and increased oxygen consumption.  This study reports the results of the administration of doxapram alone, and of doxapram in conjunction with the beta-blocker propranolol on the blood pressure, heart rate, and respiratory rate of 12 healthy unanesthetized volunteer subjects. Results showed an augmentation in blood pressure (especially diastolic), a significant decrease in heart rate, and an unexpected actual increase in respiratory rate in the doxapram/propranolol group. Subtleties of sympathetic balance, as well as proposed future studies are discussed.


Treatment of theophylline intoxication: a model study utilizing peritoneal dialysis. This study shows that peritoneal dialysis of theophylline-intoxicated rats results in withdrawal of approximately 27% of the administered dose of theophylline in 4 hr. Clinical consequences of this experience are considered.


Abnormalities of atrioventricular conduction in patients with the Lown-Ganong-Levine syndrome. In 18 patients with the Lown-Ganong-Levine syndrome and in 11 control subjects the response of the atrioventricular conduction system to heart rate acceleration by right atrial pacing, and, with the aid of His bundle electrogram, the behaviour of individual levels of the atrioventricular conduction system were studied. At spontaneous sinus rhythm A-H interval was shorter in the patients with the Lown-Ganong-Levine syndrome than in the controls. In the latter the A-H interval became markedly prolonged, up to a Wenckebach-type IInd-degree AV block, already at a minor pacing-induced acceleration of the heart rate, whereas in the patients with the Lown-Ganong-Levine syndrome the atrioventricular propagation of excitation at a 1:1 ratio remained preserved even at substantially higher heart-rate values. On the basis of the responses of the A-H interval to pacing the patients with the Lown-Ganong-Levine syndrome were classed into four types.


Epidemiology and phenotype of congenital coronary artery anomalies. Analysis of 80 cases found in necropsies of stillborn fetuses and infants. In the period from 1961 to 1974, 80 cases of congenital coronary artery anomalies in necropsies of infants and stillborn fetuses were diagnosed in the Czech Socialist Republic among more than 2.1 million consecutive deliveries. In the population thus defined the mean frequency of these anomalies was 3.8 per 100,000, with extreme values from 1.3 to 7.0 per 100,000. The epidemiological and clinical phenomena of these anomalies and their relations to selected biological-genetic and ecological factors are discussed.


Influence of vagal suppression on early arrhythmias following experimental myocardial infarction in dogs. The close relationship between disturbances of heart rhythm that follow acute myocardial infarction, and the autonomic nervous system is of particular interest. These disturbances have been attributed to the sympathetic and parasympathetic influences upon the heart. The present investigation was undertaken in order to study the influence of parasympathetic suppression on early arrhythmias following acute myocardial infarction in dogs with acute coronary occlusion. Two series were examined: control and vagotomized animals. In vagotomized dogs, the incidence of early post-infarction arrhythmias was 9 per cent against 66 per cent in the control series. The heart rate and blood pressure did not show significant changes in either series. The results emphasize the importance of the afferent and efferent vagal ways in the genesis of early arrhythmias.


Age-dependent variations in the intensity of isoprenaline-induced myocardial lesions in rats. Isoprenaline dosed 50 mg/kg was injected intraperitoneally into rats aged 42 days, 3 months, and 18 months. At intervals of 12, 18, 24, 48 hours and 5 days the degree of myocardial lesion was checked by the technetium-labeled oxytetracycline [99mTc-Sn-oxytetracycline] method. Three hours after its i. v. injection the myocardial radioactivity was measured in a control group and in the group treated with isoprenaline. Markedly higher radioactivity was found in animals given isoprenaline than in the controls. Besides, the degree of myocardial lesion considerably varied in dependence on the animals' age, being lowest in the 42-days-old and highest in the 18-months-old rats. In all age groups a biphasic alteration was observed, consisting of a phase of rapid decrease in radioactivity up to 24 hours, and a phase of slow decrease from the 24th hour till the 5th day after injection of isoprenaline. The authors consider the method using technetium-labeled oxytetracycline convenient for assessing the degree of myocardial lesion.


The effect of hypokinesis on blood clotting in rabbits. In 53 male chinchilla rabbits the effect of 14-day strict immobilization on the blood clotting and myocardial function capacity was studied. Hypercoagulability and enhancement of thrombocytic functional activity were found. The blood platelets of the experimental animals formed larger aggregates than those of the control animals. These changes were accompanied by myocardial ischaemic lesions, proved by electrocardiography.


The renal kallikrein-kinin system in various types of diuresis and under the effects of inhibitors of prostaglandin synthesis in rats. In rats with water load, rats with high-salt diet, rats treated with furosemide, and rats treated with indomethacin in low doses (2 mg/kg orally per day for five consecutive days) an enhanced urinary excretion of kallikrein was observed. Higher dosage of indomethacin (5 mg/kg), on the contrary, markedly reduced the urinary kallikrein excretion. The degree of activation of the renal kallikrein-kinin system was lowest in water diuresis, and highest at the high-salt diet. In salt- and furosemide-induced diuresis, positive correlations were found between the urinary kallikrein excretion, sodium excretion, urine flow rate, and renal concentration capacity. In water diuresis, a positive correlation was found solely between the kallikrein excretion and the urine flow rate. Indomethacin at low dosages elevated, and at high dosages reduced the activity of the renal kallikrein-kinin system; analogous effects were exerted on the urine flow rate and on sodium excretion.


[Changes in noradrenaline-induced vasoconstriction through ouabain blockade of the transmembranal electrolyte distribution]. In continuation of their studies concerning changes in the reactivity of vascular segments under isolated perfusion in vivo with simultaneous experimental disturbance of transmembranous distribution of electrolytes, the authors investigated in ten rabbits the effect of noradrenaline in the ear with isolated circulation. After perfusion of an ouabain solution (total concentration: 0.4 X 10(-5) M), in dependence on the duration of the effect of glycoside the vasoconstrictor response to 0.1 and 0.5 micrograms noradrenaline was significantly strengthened, up to 40% of the initial value. After washing-out of the vascular segment under isolated perfusion with Krebs-Henseleit solution, and ensuing restoration of normal cation relationships, the vascular reactivity returned to its initial level. Potential analogous mechanisms of the etiology and pathogenesis of essential hypertension are discussed.


Effects of atrial premature stimulation on sinus node function in isolated rabbit atria. The effects of premature atrial depolarizations (PADs) on the sinus node function were studied in isolated rabbit atria by using simultaneous intracellular recordings in the sinus node and adjacent regions. Late PADs (test cycle 85% or more of the basic cycle) did not capture the sinus node, blocking somewhere between this structure and the crista terminalis, inducing however a shortening of action potential, an increased rate of rise (Vmax) and amplitude of phase 0, and a variable depression of phase 4 depolarization on sinus node fibres. These effects were attributed to electrotonic interactions. Earlier PADs (test cycle 45--85% of the basic cycle) penetrated and captured the sinus node, changing its action potential shape, depending on the prematurity of the response. Two major effects were demonstrated: 1) a reduction in the maximum diastolic potential; 2) a linearly-related (p less than 0.001) decrease of the slope of phase 4 depolarization. These effects resulted in a depression of sinus node automaticity that was inversely-related to the test cycle length. Dominant pacemaker shifts within the sinus node were frequently observed with early as well as with late PADs resulting in a change of the basic cycle by as much as 90 msec. It is concluded that the use of the technique of premature atrial stimulation may not permit precise evaluation of sinoatrial conduction time.


Modification of plasma dopamine-beta-hydroxylase activity by adrenal and pineal extirpations, and time of day dependency of changes. Plasma level of dopamine-beta-hydroxylase (DBH; EC 1.14.2.1) activity has been considered important both as a diagnostic aid and as an indicator of temporal changes in sympathetic activity. The present study sought to evaluate the possible dependency of some phases of the circadian rhythm in plasma DBH on adrenal and pineal glands. Male Holtzman (albino) rats were shamoperated, adrenalectomized (AX), pinealectomized (PX) or both adrenalectomized and pinealectomized (AXPX) at 32-35 days of age and after acclimation to controlled conditions with a fixed, 12-h, daily photoperiod (LD 12:12). Animals were killed at selected times 15 days postoperatively, and plasma DBH was measured using a sensitive radioenzymatic method. Results from two successive experiments showed that there was significant reduction in plasma DBH in the AXPX animals, but that this was evident only during the middle of the dark phase. PX and AX alone did not bring about any change in the DBH activity at any of the two times tested. These results show that combined endocrine manipulations can alter the circulatory DBH activity level and that such changes can be evaluated only within the definition of a circadian pattern.


Circadian susceptibility rhythm of the rat to alloxan. The susceptibility of rats to alloxan undergoes a circadin rhythm. The toxicity rhythm, presumably involving injury to liver, kidney and other sites, pancreatic beta-cells in particular, is demonstrated in pooled data from 370 mature inbred Fischer or Minnesota Sprague-Dawley rats of both sexes kept in light from 06(00) to 18(00) alternating with darkness, some with free access to Purina laboratory chow with tap water at all times and some other rats subjected to one of three starvation schedules: 1) a 28-h fast before an intravenous alloxan injection; 2) a 28-h fast, except for a 4-h ad libitum feeding before injection; 3) a 28-h fast, except for a 4-h pre-injection tube-feeding of Nutrament (Mead and Johnson, Evansville, Indiana), 1.5 ml/100 g body weight. Survival time data on an additional 200 inbred Fischer rats reveal, next, that susceptibility to alloxan increases as the starvation span is lengthened from 24 to 84 h. The shortening in survival time indicative of this susceptibility increase is nonlinear; a circadian rhythmic change in susceptibility to alloxan is seen as a statistically significant wave-form indicative of the basic (persisting) rhythm, of applied interest as well to students of experimental diabetes.


The response of glucose, insulin and FFA to intravenous glucose and glucagon in elderly subjects in the course of morning and afternoon tests. The response of glucose, FFA and immunoreactive insulin to intravenous glucose and glucagon was examined in 6 apparently healthy subjects aged 67-77 years at 08(00) and 18(00) with a 3 day interval. The subjects, fasted 12 h before each test, received 0.5 g/kg of glucose i.v. and, 40 min after glucose, 1 mg glucagon i.v. The results confirmed, also in aged subjects, an impaired glucose tolerance in the afternoon test, as previously reported in the adult subject. The insulin response was delayed in the afternoon test, but the total incremental area was not significantly reduced. There was not a clearcut difference in the pattern of FFA response. The results could be a further confirmation of the central role of insulin response as a cause of impaired glucose tolerance in the afternoon also in subjects aged over 65 years.


Coincidence of adjacent periodicities of men investigated with the pergressive Fourier analysis. The body temperature of 2 persons closed off to the outside world was pergressively analyzed with a short analyzing interval showing that the spontaneous and controlling rhythms of T = 30 h are present as previously demonstrated by ASCHOFF and BLUME. The characteristic properties and differences of both curves are described. Especially it is demonstrated that a transient process is present in the first curve, but not in the second curve. The presence of both rhythms is confirmed by the pergressive Fourier analysis of the first curve with a long analyzing interval. The problem to find out correct values for the parameters of hidden rhythms with the aid of the amplitude spectrum is pointed out. It is not present for the pergressive Fourier analysis.


Circadian and circatrigintan rhythms in pulse, oral temperature and blood pressure of a clinically healthy Japanese woman. The circadian and circatrigintan (menstrual) system of a healthy Japanese woman has been quantified by single cosinor analyses. The results obtained at only 2 frequencies are discussed against the background of prior chronobiologic information. The paper documents different acrophase relations of rhythms with different frequencies in the same variables and includes a sketch of the position of the single cosinor method as a tool in a methodologic armamentarium of broader interest in anthropology, medicine and more generally in biology.