Amino acid incorporation into total protein and levels of S-100 protein in discrete rat brain areas after prolonged protein or amino acid restriction.

Young adult rats were fed an isocaloric diet for 28 days. The diet consisted of either 22% casein, or protein-restricted food consisting of a 5% mixture of soy and whey protein, or a synthetic amino acid mixed diet devoid of the essential amino acids tryptophan, valine, lysine, and threonine. The level of the nervous tissue-specific S-100 protein was quantified immunoelectrophoretically in 9 different brain areas. A marked decrease of S-100 was observed in hippocampus and posterior part of the cerebellar vermis per g wet weight in protein-restricted rats. An additional lowering was noticed in sensory motor cortex per mg soluble protein. This effect was potentiated with the amino acid-deficient diet. The in vitro incorporation of 3H-leucine into cerebellar proteins was slightly decreased in the low-protein-fed rats, and more markedly decreased in those receiving an amino acid-restricted diet.


Failure of hepatic infusion of amino acids and/or glucose to inhibit onset of feeding in the deprived dog.

Nine mongrels dogs were fed for only 1 hour/day for 7-8 days and the time of onset of their eating and hourly intakes were recorded. At the end of this period, the hepatic portal vein was cannulated and the polyethylene cannula was exteriorized. Upon recovery to their preoperative food intake, the dogs were infused after a 23 hour fast over a 4 minute period with an amino acid (AA) mixture (FreAmine II, McGaw Laboratories) equal to 7.2% (37 trials), 14.4% (28 trials), or 21.6% (28 trials) of the dogs' daily AA requirements and presented with food 4 minutes later. In all 93 trials the dogs ate within 30 seconds of presentation of food and their hourly intakes were not significantly different from isotonic saline infusions. Six 23 hour deprived dogs were infused with 21.6% of their AA requirement and then presented with food 11 minutes later. Again, these dogs began eating within 30 seconds of presentation of food. Finally, 4 dogs were infused over a 4 minute period after a 23 hour fast (12 trials) with 7.2% of their daily AA requirements mixed with 6 g of glucose and presented with food 4 minutes later. The dogs began eating within 30 seconds in all 12 trials and their hourly intakes were not significantly depressed. These results question the existence or role of hepatic glucoammonium receptors involved in the control of feeding behavior.


[Renal-rachidian venous trunk. Replacement of the left renal vein. A danger for the spinal cord (author's transl)].

In two cases of paraplegia due to an inondation of the intrarachidian plexus by venous blood from the left venal vein, we studied the frequency with which the renal-rachidian trunk connected the left renal vein and the intrarachidian plexus. We show in these rare cases how it is possible, with a simple procedure, the ligature of the renal-rachidian trunk, to bring about a marked regression in the paraplegia. This procedure has been carried out five times, and it should be seen within the wider framework of a serie of procedures on the cava system, which are now practised for more than forty years.


[Hydronephrosis due to pelvi-ureteric junction syndrome in the adult and child 3 reports (78 adults and 33 children) representing 118 hydronephrosis (author's transl)].

The following main points emerge from this analysis: -- Whilst all cases of hydronephrosis do not require operation, in the long term future of a non-operated hydronephrosis is difficult to predict and the risk of avoiding surgery is not definitely less than that of operation. -- Adult hydronephroses are much more often complicated by lithiasis (16 cases in 82 hydronephrotic kidneys) than those seen in children (4 cases in 36 hydronephrotic kidneys). -- The prognosis if hydronephrosis, especially with lithiasis, affecting a horseshoe kidney is particularly poor, without there being any clear explanation for this fact. -- Anderson-Hynes plasty of the pelvi-ureteric junction would seem to be a reliable operation, even more in the child than the adult. However, even when carried out perfectly, it provides no gaurantee against the development or secondary development of lithiasis, even when dilatation and urinary stasis have disappeared. Thus very prolonged surveillance is necessary after such surgery, above all when the hydronephrosis was accompanied by lithiasis.


[Wide abdominothoracic approach for a tumor on the superior pole of a horseshoe kidney; supra and subumbilical median and anterolateral oblique thoraco-phrenic laparotomy (author's transl)].

The development of a tumor on the superior pole of a horseshoe kidney is an event which, although rare, still presents the surgeon very specific problems related to the anatomy of the malformation. The presence of a parenchymal pons, the multiplicity and anomalies in the origin of arteries are all factors to be taken into consideration in the selection of a surgical procedure. It is of particular importance that the approach be very wide in order to combine the advantages of the trans-peritoneal approach with that of the thoraco-phrenic laparotomy. One case is presented, and the surgical solution is discussed.


[Radiation and the kidney (author's transl)].

The kidney is highly radiosensitive. Analysis of the literature indicates that the threshold dose is 2 350 rads in 5 weeks. A number of clinical examples are used to illustrate the precautions which must be taken by the radiotherapist in order to avoid the provocation of radiolesions whilst delivering a curative dose to the tumor.


[Nephrectomy for infantile hypernephroma. 30 years cure (author's transl)].

The study involves the treatment of infantile hypernephroma. It shows that, as in the adult, 30 years cures may be obtained.


[Sigmoid kidney accompanied by the absence of uterine tubes, uterus and vagina (author's transl)].

The author reports a rare case of sigmoid kidney accompanied by the absence of uterine tubes, uterus and vagina, and stresses the importance of thorough investigation of both the urinary and genital systems in the presence of a malformation affecting one or the other.


[Kidney trauma in a 13 years old child with voluminous bilateral hydronephrosis (author's transl)].

This is a report of a case of bilateral renal trauma. Acute rupture of the right kidney and bilateral hydronephrosis with significant parenchymal destruction are described. Unusual surgical cure is reported.


[Traumatic rupture of the isthmus of a horseshoe kidney (author's transl)].

In the light of an extremely rare case of rupture of the isthmus of a horseshoe kidney, the author described the operative technique used and the postoperative complications which, despite their gravity, could be controlled by conservative operative measures.


[Clinical study of carfecillin in chronic urinary tract infection (author's transl)].

1. Ten patients with chronic urinary tract infection by Pseudomonas aeruginosa or Proteus species were treated with carfecillin. Excellent response was seen in one case, fairly good in 5 cases and clinical effective rate was 60%. 2. The recurrence suppression effect of carfecillin was examined in two patients suffering from complicated urinary tract infection. In both cases, recurrence was not found when carfecillin was administered for a week after the effective pretreatment of carbenicillin, but found when administered for two weeks. 3. Side effects were observed in 3 cases (itching, tinnitus, diarrhea).


The structure of triglyceride in human sebum.

1) A relatively large quantity of branched chain and odd-carbon-number fatty acids were found in human sebum. 2) These acids were present in each lipid fraction (cholesterol ester, triglyceride and free fatty acid) of sebum. 3) In the triglyceride molecule, these acids were found mainly on the 2-position.


Studies on the fresh water cercariae in Leyte Island, Philippines. 4. Cercariae from Viviparidae and Pilidae.

During the period of 1975 and 1976, about two thousand snails of Viviparidae and two hundred snails of Pilidae were examined for cercarial fauna on Leyte Island, Philippines. From the snails of Viviparidae, 8 species of cercariae were found. These species consisted of two furcocercous cercariae, one monostome cercaria, three echinostome cercariae and two xiphidiocercariae. From the snails of Pilidae three species of cercariae were found; namely, one echinostome cercaria, one xiphidiocercaria, and one unknown cercaria. Among these species, one echinostome cercaria and one xiphidiocercaria were found to be common to snails of both families. In this paper these nine species of cercariae were described and illustrated with some remarks on their presumptive life cycles.


Production of guinea pig reaginic antibody against the house dust mite extract, Dermatophagoides pteronyssinus, without adjuvant.

Guinea pigs of Hartley strain were sensitized with an extract of the house dust mite, Dermatophagoides pteronyssinus. Positive immediate skin reactions were obtained in more than half of the animals 6 weeks after repeated intradermal injection. Adjuvants of A1(OH)3 gel or Bordetella pertussis vaccine did not significantly enhance the production of reaginic antibody. Prausnitz-Küstner type skin test titers were even higher in guinea pigs sensitized with the mite extract without adjuvant. Circadian rhythm and difference in injection sites were not noted when assessed by skin tests on sensitized guinea pigs. Passive hemagglutination test detected serum antibodies and some animals showed respiratory distress on the challenge with the aerosolized extract. This system would be an another useful laboratory model of acute respiratory allergy of the most important inhalant allergen, the house dust mite.


Establishment of epithelial cell lines from rat glandular stomachs.

Nine epithelial cell lines were isolated from glandular stomach cells of fetal and suckling JAR-2 rats after the elimination of mesenchymal cells by mechanical and colonial isolation methods. Those cells have been proliferating continuously in a typical pavement-like arrangement. In early cultures a part of focal monolayers of small epithelial cells died simultaneously ("contact death"). The cells of three lines (RGS-2,RGS-5 and RGS-8) formed hemicysts when incubated for several weeks without subcultivation. Addition of But2cAMP and theophilline into culture medium enhanced the hemicyst formation by RGS-8 cells. Some evidence suggested that those three lines were originated from mucous epithelium of rat glandular stomach. These epithelial cell lines would be useful in the study of chemical carcinogenesis in culture.


Modification of cortically evoked rhythmic jaw movements by reflex deglutition in rabbits.

In rabbits, lightly anesthetized with ether, tetanic stimulation of the superior laryngeal nerve (SLN) displaced the jaw toward opening and reduced the amplitude of cortically evoked rhythmic jaw movements. With increased intensity of stimulus, the effects became remarkable and the opened jaw movement ultimately ceased. Reflex swallowing in reaction to weak electrical stimuli of SLN or to a small amount of water squirted into the oropharynx yielded a brief and instantaneous cessation of rhythmic jaw movements with the jaw open. Strong electrical stimuli to the nerve or a squirt of relatively large amount of water into the oropharynx prolonged the duration of both swallowing and the cessation of rhythmic jaw movements for about 1.0 sec. Reflex swallowing yielded a burst of activity for about 300 msec in the mylohyoideus and silence for a longer period in the masseter. Spontaneous activity of the masseter was moderately decreased during the nerve stimulation and, when swallowing occurred, this decrease became prominent for a short period.


Origin of the secondary response induced by flash stimulation under barbiturate anesthesia in the rabbit.

The photically evoked secondary response of the visual cortex was studied in a rabbit anesthetized with pentobarbital sodium. The following results were obtained: 1) The secondary response (P2) under anesthesia was a simple positive potential having a long latency and resembled the primary response (P1) in waveform. 2) The latency of P2 shortened gradually as the recovery from anesthesia proceeded. 3) P2 was usually smaller than P1 in amplitude when evoked with a strong flash, but larger than P1 when evoked with a weak flash. 4) Electrical stimulation of the superior colliculus (SC) induced in the visual cortex a positive potential which had a long latency comparable to that of P2. On the contrary, stimulation of the lateral geniculate body (LGB) evoked a short latency, positive potential similar to P1, but failed to evoke a positive potential comparable to P2. 5) A partial lesion of LGB led to a decrement of P1, while lesion of SC resulted in a decrement of P2. 6) Cooling of SC resulted in a rapid reduction and disappearance of P2 as well as the negative potential in SC. 7) There were a considerable number of visual cortical neurons which fired commonly during the phases of P1 and P2. These results suggest that P2 might be derived through the extrageniculo-cortical system which is relayed at SC. The mechanism by which P2 was manifested under anesthesia was discussed.


Relation of protein nutrition to the reduction of red blood cells induced by physical training.

Sports anemia induced by tennis training or exercising on a bicycle ergometer was studied in healthy male students. Since the anemia has been attributed to an increased susceptibility of red blood cells to lysis during exercise and influence by the nutritional status of the individuals has been suggested, the relation of sports anemia to the nutritional conditions of the subjects and to osmotic fragility of red cells were studied in groups by controlling protein levels in diets. Anemia was most pronounced and the recovery from it was most prolonged in subjects with low protein diets, while it was least pronounced and the recovery was most rapid in subjects with high protein diets. The extent of increase in osmotic fragility of red cells was highest in subjects with low protein diets, and lowest in subjects with high protein diets. The erythropoietic responses to the exercise were different among the dietary groups; i.e., an early increase in blood reticulocytes in subjects with high protein diets and a late increase in subjects with low protein diets were observed during the course of training. From above observations, we conclude that the extent of anemia is closely related to protein intake from the diets and that it is one of adaptive processes of individuals to stenuous physical training rather than an exaggeration of the physiological process of erythrocyte destruction.


Fall in skin temperature during exercise.

During light work using the arm in a warm environment, skin temperatures of the arms and chest fell and remained at lower levels during work. The fall in skin temperature during work was not observed in a cool environment. The fall in skin temperature was nearly proportional to work intensity and was observed in both static and dynamic work. Leg work of moderate intensity produced an initial decline and a subsequent rise in skin temperatures of the hands, thighs and legs. A significant fall in skin temperature was observed not only in the foot but also in inactive regions such as the epigastrium. The mean skin temperature remained practically unchanged during work. The fall in skin temperature during work was not due to increased evaporative cooling, but was the result of segmental vasoconstriction probably caused as a reflex in the spinal cord by non-thermal afferents from exercising muscles or moving tissues. The effect of thermoregulatory vasodilation was reduced by the reflex vasoconstriction caused by non-thermal factors. The rise in internal temperature during work could be explained by decreased heat loss due to persistently lower skin temperature.


Influence of intestinal inhibitory reflex on mesenteric blood flow through an intestinal segment of the dog.

The variations in both tonus and rhythmical motility of the intestinal musculature are known to affect profoundly intestinal blood flow. In the present study, the influence of marked reflex inhibition of intestinal tone on the blood flow through an intestinal segment was investigated in the dog. Experiments were performed under conditions of both normal circulation and cross-circulation. Inhibitory reflex was elicited by elevating the intraluminal pressure of a loop or by electrical stimulation of the intestinal wall. Fluctuations of blood flow during the intestinal inhibitory reflex were observed with normal circulation. Arterial and venous blood flows decreased in the initial period of intestinal relaxation, and recovered within 30 sec although reflex inhibition still remained. This is an autoregulatory escape phenomenon. In successive periods, arterial and venous blood flows decreased again due to "the venous-arteriolar response" and then recovered to the quiescent level. The decrease in venous blood flow corresponded to an increase of the degree of oxygen saturation in the venous blood. The decreases in arterial and venous blood flows were observed during the inhibitory reflex even when the intestinal circulation was maintained by the cross-circulation. Two different patterns, i.e., the parallel and reversed patterns, were distinguished in correlation with venous blood flow and oxygen saturation. The autoregulatory escape phenomenon could not be elicited in the experiments in the cross-circulation system because variation of the systemic blood pressure during inhibitory reflex was limited to +/-4%.


The mechanism of Ca2+ action on the healing-over process in mammalian cardiac muscles: a kinetic analysis.

The effect of Ca2+ concentration and temperature on the recovery of membrane potential after investigating lesions using sucrose-gap technique in the guinea-pig papillary muscles were studied. At certain temperatures, this recovery showed increased accerelation with increasing Ca2+ concentration. The relation between rate constant of the recovery and Ca2+ concentration was quite similar to that of the reaction between an enzyme and substrate. This relationship could be expressed by the equation Y = xn(Km + xn), where Y is the normalized rate constant and x the Ca2+ concentration. The coefficient, n, was evaluated by performing Hill's plot. The value of n largely changed between 1 and ca. 2 at 32 degrees C--37 degrees C. The input resistance fell at the instant of formation of a lesion and started to rise with recovery of membrane potential. The resistance change after lesion formation was also observed in the potassium-Tyrode's solution in which Na+ was substituted with K+. The concentration-rate relationship of Ca2+ in the healing-over seems to indicate that Ca2+ binds to some molecules in the junctional membrane and produce a structural change of intercalated disc which brings about the healing-over. The large change of n suggests that Ca2+ has a cooperative action in the healing-over process, or alternatively that the state of membrane lipids has some effect on the process.


Effects of caffeine and procaine on the membrane and mechanical properties of the smooth muscle cells of the rabbit main pulmonary artery.

Effects of caffeine and procaine on the membrane and mechanical properties of the smooth muscles of the rabbit main pulmonary artery were investigated using microelectrode and voltage clamp methods. Caffeine (greater than 0.5 mM) depolarized the membrane and increased ionic conductance. On the other hand, procaine (greater than 2.5 mM) depolarized the membrane, generated spikes and reduced the ionic conductance of the membrane. When depolarization-contraction relations were observed, the threshold depolarization to evoke contraction and the amplitude of the contraction were not affected by 5 mM procaine. However, the mechanical threshold was raised and the mechanical response was suppressed by treatment with 5 and 10 mM caffeine or 10 mM procaine. Procaine and caffeine accelerated the depletion of Ca++ from the stored sites of Ca-free (EGTA) solution, and suppressed the mechanical responses induced by chemical stimulation. Caffeine and procaine suppressed the increase in ionic conductance and depolarization produced by noradrenaline or prostaglandin F2alpha. Caffeine also suppressed the mechanical response induced by the above agents. Procaine suppressed the noradrenaline induced contraction, but accelerated the prostaglandin F2alpha induced contraction. From the above results, it is concluded that caffeine and procaine act not only on Ca-stored sites in the cell but also on the surface membrane. The actions of these agents were not competitive with each other, thus suggesting that the properties of the internal membrane structures, which is assumed to be a main Ca-storage site, are not exactly the same as those in striated muscles.


Force-load-velocity relation and the internal load of tetanized frog cardiac muscle.

A frog ventricular muscle strip could be fully tetanized by alternating current stimulation at 10 Hz and 20 V/cm in a solution containing 9 mM Ca2+. During isometric tetanus, the controlled release was made and the shortening velocities against various loads were measured. The isometric force was varied by reducing the stimulus intensity in K+-rich solution, or by reducing the external Ca2+ concentration. The force-load-velocity relation was described by a simple hyperbolic equation: (P+A)(v+b)=b(F+A), A=(F/Fm)a for shortening, and (2F-P+A')(-v+b')=b'(F+A'),A'=(F/Fm)a' for lengthening, where F is the isometric force, Fm is the maximum isometric force at the optimal muscle length, Lm, P is the load, v is the velocity, a, b, a' and b' are constants. The values of constants were a/Fm=0.51, b=0.75 Lm/sec for shortening and a'/Fm=0.39, b'=0.75 Lm/sec for lengthening at 20 degrees C. At muscle lengths shorter than 0.92 Lm, the internal load defined as the difference between the external load and calculated load at a given velocity increased in proportion to both the velocity and the decrease in muscle length.


[Perception of schizophrenic patients in classifying pictures of facial expression].

The purpose of this study was to investigate the perception of schizophrenics in classifying pictures of various facial expressions. Schizophrenics were divided into five groups according to the duration of their hospitalization. In the first experiment, subjects were instructed to look at the pictures of three different kinds of facial expressions, anger, delight (laughing) and sadness (crying), and classify them into any categories they like. In comparison with normals, schizophrenics had a difficulty in recognizing the differences in the various facial expressions. In the second experiment, subjects were instructed to look at the same pictures and classify them into three groups of different facial expressions. In this case, schizophrenics were able to classify them almost as well as normals.


[Characteristics of manifestation of myocardial pathology at the cellular-molecular level under experimental conditions and in rheumatic heart diseases].

By applying the microelectrode technique the character of membranous potentials of pathologically changed cells of the myocardium in experiments and in rheumatic disease was studied. Experimental investigations were carried out on an original model of tonsillogenic myocardiodystrophy reproduced in rabbits through a prolonged mechanical stimulation of receptors in the peritonsillar region. The iono-molecular disturbances in the myocardial cells manifested themselves in reduced duration of the action potential, of its refractory period and in the decreased rate of the excitation conduction along the myocardium. The educed changes in the electrical activity of the myocardium cells depend upon the deranged work of slow sodium-calcium pumps associated with the sarcoplasmatic reticulum and testify to deviation, to a certain extent, from the normal of all the myocardium functions, viz. conduction excitability and contractility. The similar nature of electrophysiological changes in the myocardium cells in experiments and in rheumatic disease are a proof of the unity of pathogenetic mechanisms of cardiac lesions at the cellular-molecular level.


[Origin of the deep and wide T-wave in myocardial diseases].

The presented analysis concerns the clinical and electrocardiographic data of dynamic examinations of 15 patients in whom ECG recorded a deep and wide ("gigantic") inverted T-wave. In 5 cases the clinical and electrocardiographic data were compared with the anatomic ones. It was demonstrated that a wide and deep inverted T-wave is common in ischaemic heart disease and inflammatory lesions. Focal myocardial lesions (predominantly in the ventricular septum) combined with atrioventricular conductivity disorders in the His-Purkinje system were found to play a definite role in the genesis of the "gigantic" T-wave. In some cases the wide T-wave may develop due to a fusion of T and U-waves. Patients with such ECG alterations suffer severe rhythm disorders in the form of frequent polytopic extrasystoles, paroxysmal ventricular tachycardia, ventricular fibrillation.


[Tissue reactins in the heart in disorders of its adrenergic innervation].

Cardiac tissue structures reaction was studied under conditions of decreased general sympathic mediation and disturbance of the direct connections between the heart and the sympathetic nervous system. Antibodies to the nerves growth factor with a strict selectivity to affect adrenergic neurons, localized in the sympathetic chain were used in the experiment for cutting out the sympathetic part of the vegetative nervous system. The data received permitted the authors to solve positively the problem of the sympathetic neurotrophical influence on the vascular components and cardiomyocytes.


[Various humoral pressor and depressor systems in hypertension].

Study of the hormone content and enzyme activity in patients with hypertensive disease at rest and in various types of stimulation revealed predominance of pressor humoral systems over depressor ones. With the development of the disease, the reaction of these humoral systems to stimulation diminishes. Decrease of the renin-angiotensin-aldosterone system compensatory reaction and the prostaglandin F level in patients with stable, high arterial pressur in response to furosemide administration may be among the causes of the hypotensive and natriuretic effect of this preparation. Activization of the humoral depressor systems in the initial stage of the disease is conducive to the preservation of the water-electrolyte hemostasis in the organism and maintains the labile level of arterial pressure despite the increased activity of the natrium-retaining hormones. Exhaustion of the humoral depressor systems may be one of the causes of arterial pressure stabilization.


[Changes in the antidiuretic activity of the blood in hypertensive crises and experimental arterial hypertension of hypothalamic origin].

The blood antidiuretic activity was studied in patients with hypertensive disease in a period between crises and during a hypertensive crisis. The antidiuretic activity of blood was found to be higher in patients who had crises than in those with no history of crises. Blood antidiuretic activity diminishes during a hypertensive crisis, which is evidently due to the inhibiting effect on the hypothalamus of the receptors of the cardiovascular system. Similar results were obtained in experiments in elevation of arterial pressure induced by electric stimulation of the hypothalamic nuclei. It is concluded that the antidiuretic hormone plays a pathogenetic role in hypertensive disease which is marked by the development of crises.


[Plasma aldosterone concentration and vascular reactivity in hypertension].

Aldosterone concentration in peripheral plasma (radioimmune assay) and vascular reactivity (by an original tracer method) were determined in 50 patients with essential hypertension of stages I and II and in 25 healthy males. Aldosterone concentration proved to be elevated in half the patients, mostly in those with stage II of the disease. Vascular reactivity in these patients was increased and the two parameters were in good correlation. In the other group the aldosterone level and vascular reactivity were normal and there was no correlation between these two parameters. It is concluded that in some patients with essential hypertension aldosterone plays a pathogenetic role by increasing vascular reactivity.


[Change in plasma renin activity in patients with hypertension and healthy persons after furosemide intake].

Blood plasma renin activity was studied by the radioimmune method in clino- and orthostatism in 36 males with hypertensive disease and in 15 healthy males before and after 3-day medication with furosemide in a daily dose of 120 mg under in-patient conditions. Renin activity proved to be higher in double stimulation (in orthostatism after furosemide intake) than in orthostatism before the intake of the drug. Diversity was revealed between patients with different stages of hypertensive disease. Stage IB of the disease was characterized by increased renin activity in orthostatism and marked reaction to stimulation with furosemide. In stage IIB, on the contrary, renin activity was low and the reaction to stimulation with furosemide weak. Hypotensive effect after intake of furosemide was observed in patients with IIB stage of hypertensive disease.


[Kallikrein-kinin system of the kidneys in hypertension under different conditions of examination].

Changes are observed in the renal kallikrein-kinin system in hypertensive disease, which are displayed by compensatory increase in its activity in patients with labile hypertension and decrease in the activity of this system in patients with a stable stage of the disease. An inadequate reaction to a load experienced from walking or from a reduced volume of extracellular fluid and sodium balance in the body was noted in all stages. The absence of a reaction or the inhibition of the activity of the renal kallikrein-kinin system in response to the intake of furosemid may be a manifestation of its altered sensitivity to the electrolyte shifts in the organism and the decrease in the volume of extracellular fluid. The kallikrein-kinin system is concerned with the noted shifts in renal function linked with the transport of sodium and water in patients with the labile stage of the disease, to which the correlative connection between kallikrein excretion and natriuresis and urine excretion attests. It is suggested that the renal kallikrein-kinin system in patients with the initial stage of hypertensive disease contributes to the adaptation of renal function to the altered conditions of hemodynamics and the increased activity of the renin-angiotensin-aldosterone system.


[Value of puncture biopsy of the kidneys on the side of the stenosis in renovascular hypertension. I].

The morphological picture of bioptic renal tissue was studied in 23 patients with different forms of vasorenal hypertension, among whom 12 had fibromuscular dysplasia of the renal arteries, 8 had atherosclerotic stenosis, and 3 had panarteritis of the aorta and its branches with involvement of the renal arteries. The syndrome of malignant hypertension was encountered in 13 patients and stable arterial hypertension with high blood pressure levels in 10 patients. Analysis of the bioptic material allowed it to be divided into two groups: the 1st was marked by a picture of "Selye's kidney" and the 2nd by a combination of stenosis of the renal arteries and parenchymatous diseases of the kidneys. The significance of examining the morphological picture of renal bioptates, both with regard to the study of the pathogenesis of vasorenal hypertension and the diagnosis of concomitant parenchymatous process is shown.


[Changes in central and regional hemodynamics during treatment of hypertension with hemiton].

The indices of central hemodynamics were studied during hemiton therapy in 33 patients with stage IIA and IIB hypertensive disease by means of a noninvasive method--tetrapolar chest rheography. In patients with hypodynamic type of circulation the arterial pressure decreased already beginning with the first week of treatment due to a decrease in the arterial tonus and general peripheral resistance; the cardiac output practically did not change. During treatment cerebral and peripheral circulation improved significantly (according to the rheographic data) and the arterial tonus decreased. In 3-4 weeks of treatment, favourable shifts occurred in the reactions of general and regional hemodynamics in the orthostatic test. The overall changes were evidence that the compensatory-adaptational reactions of the arteries and veins had improved and the venous return had increased. In most patients treatment with hemiton led to lesser orthostatic decrease in arterial pressure and its greater lability during the day.


[Use of the adrenergic beta receptor blockader, visken, (prindolol) in arterial hypertension].

Visken (prindolol) was used in 42 patients. Its hypotensive effect was studied by the double-blind method. The hypotensive effect was encountered in 34 patients. With the administration of a placebo the arterial pressure became elevated, while after repeated prescription of the drug it again decreased significantly. Study of hemodynamics by radiocardiography in 18 patients treated with prindolol revealed no essential changes in the cardiac output, total peripheral resistance, rate of venous blood flow and volume of circulation.


[Change in the coagulative properties of blood under the effect of physical exertion in patients with hypertension].

Changes in the coagulation properties of blood under the effect of physical exertion on a bicycle ergometer were studied in 111 patients with hypertensive disease. The activity of their blood coagulation system was found to be increased and fibrinolysis simultaneously intensified as compared to these values in healthy persons. The degree of these changes depended on the age of the disease and the load of the exertion. Effective hypotensive therapy improved the functional condition of hemostasis, intensifying the activity of the anticoagulation mechanisms among others.


[Intracardiac hemodynamics and clinico-pathogenetic variants of the course of hypertension].

In 187 patients with different stages of hypertensive disease, besides studying the calculated values of systemic hemodynamics (minute volume, total peripheral vascular resistance), echocardiography was used to study values characterizing the state of intracardiac hemodynamics: end-diastolic (Vd), end-systolic (Vs), and stroke (Ve) volumes, the ejection fraction (EF), and the left ventricular myocardium mass (MM). According to the value of the minute volume (MV) and the total peripheral vascular resistance (TPVR), the patients were divided into 2 main groups--with hypo- or hyperdynamic type of circulation. In accordance with the values of intracardiac hemodynamics, 2 subgroups were conditionally distinguished among the patients with hyperdynamic-type circulation: the first subgroup was composed of patients with comparatively low Vd, Vs, and Ve values and moderate increase in MM, the second subgroup of those with high Vd, Vs, Ve, and MM values. It is shown that with gradual progression of hypertensive disease the number of patients in the second subgroup increases and the number of those in the second subgroup decreases, respectively. Parallel study of the functional state of the sympatheticoadrenal and renin-angiotensin systems showed their activity to be higher in patients of the first subgroup with hyperdynamic type of circulation. Comparatively new hemodynamic aspects of hypertensive disease connected with the contribution of the heart itself to the pathogenesis of the disease are discussed. It is suggested that among patients with hypertensive disease there are individuals with predominant and early involvement of the heart in the pathological process with rapid development of left ventricular hypertrophy.


[Role of the natriuretic factor in the phenomenon of "exaggerated natriuresis" in experimental hypertension].

Water and electrolyte excretion after a salt load, plasma natriuretic activity, and sensitivity of the kidneys to the natriuretic factor were studied in experiments on Wistar rats with renal hypertension and on SHR rats with spontaneous hypertension. The "exaggerated natriuresis" phenomenon is observed in animals with hypertension after a salt load. The plasma natriuretic activity in rats with experimental hypertension does not rise in response to an increse in the volume of extracellular fluid. The sensitivity of the kidneys to the natriuretic factor in animals with experimental hypertension is the same as that in the control animals. Consequently, the natriuretic factor has no decisive role in the "exaggerated natriuresis" phenomenon in these types of experimental hypertension.


[Role of prostaglandins in blood pressure regulation].

Experiments were conducted on 119 male and female mongrel/albino rats and on 5 male rabbits to study the mechanisms of the in vivo effect of the inhibitors of the biosynthesis of prostaglandins, acetylsalicylic acid, and indometacin, taking into account the previously obtained data on the fact that these inhibitors elevate mean arterial pressure and increase vasopressor sensitivity to adrenalin and noradrenaline in experimental animals. It was found that these inhibitors of prostaglandin biosynthesis promote the development of "salt hypertension" in rats against the background of a noticeable increase in vasopressor sensitivity to catecholamines. Intravenous administration to rabbits of angiotensin-11 in pressor doses causes an increase in the content of group E prostaglandins in the blood plasma of rabbits and a decrease in the renin activity ("feedback" effect). The data obtained have confirmed the assumption that prostaglandins take part in the arterial pressure control and suggested that in exhaustion or hereditary deficiency of the function of the prostaglandin production system the vessels may escape the depressor control, in this case the sensitivity to pressor factors increase and stable arterial hypertension develops.


[Absorption and metabolism of 14C-noradrenaline in the ischemic rabbit kidney].

Absorption (capture) and metabolism of exogenous 14C-noradrenalin (14C-NA) by the renal tissue were studied in rabbits with artificially induced ischemia of the kidney and in control normotensive animals subjected to sham operation. We treated the tissue by our modification of the methods suggested by Whytly at al. (1961) and Kopin et al. (1961). The experiments were conducted on 49 chinchilla rabbits. The experimental and control animals were killed in groups, 1,4, and 8 weeks after the operation. The results obtained were expressed in percentage of the administered radioactivity dose per 200 mg of tissue. It was determined that the degree of 14C-NA capture by an ischemic kidney decreased in the 1st and was restored in the 4th and 8th postoperative weeks. At the same time, the production of 14C-normetanephrine- and 14C-vanillylamygdalic acid in the ischemic kidney was delayed; the amount of unchanged 14C-NA and 14C-dihydroxyamygdalic acid increased. The absorption and metabolism of 14C-NA in intact (nonischemic) kidneys did not differ essentially from those in the kidneys of the control animals.


[Degree of vascular tonus as a factor of changes in the reactivity of the smooth muscle structures of the blood vessels].

The activeness and functional orientation of the responses of isolated vascular segments to electric stimulation depends on the initial tonic tension. A relatively low degree of extension of the preparations corresponding to a low intravascular pressure creates a tendency towards a response in the form of relaxation. Stimulations of the same intensity cause contractions against the background of a more significant extension of the preparations observed in cases of high pressure. The constrictive effects occuring against the background of significant vessel extensions are interpreted as a manifestation of inadequate responses, similar to the hyperreactivity noted in hypertension.


[Biomechanical porperties of the human coronary arteries].

Biomechanical properties of the coronary arteries were studied according to age and localization of the vascular segment. Experiments were conducted on the proximal and distal segments of the right coronary artery and the anterior descending branch of the left coronary artery in 58 males who ranged in age from 15 to 83 years. Vascular segments prestretched in the longitudinal direction experience an inner pressure of 0 to 240 mm Hg. The main parameters of the mechanical properties of the coronary arteries were determined. Changes in these properties were most marked in the proximal part of the left coronary artery, the deformative capacity of its walls in the circumferential direction being diminished by the end of the fourth and the beginning of the fifth weeks. The right coronary artery experiences less changes than the left coronary artery.


[Division of the 45- to 59-year-old male population into groups depending on the risk factors in a prophylactic study of ischemic heart disease].

A prospective study was conducted from March 1972 to November 1976 in a group of Kaunas male population ranging in age from 45 to 59 years. At the beginning of the study it consisted of 3,553 individuals. They were divided into groups of low, moderate, and high risk according to the presence of a risk factor (hypertension, hypercholesteremia, impaired glucose tolerance test) and a pathologic condition. The ratio of the total mortality rate per 1,000 of the population during the observation period in these groups was 1 : 2 : 3, while that of the mortality of ischemic heart disease was 1 : 3 : 5. The rate of out-patient coronary mortality and the occurrence of new cases with myocardial infraction according to their number registered in the groups of low, moderate, and high risk was 1 : 2 : 5. All the indices in the group of individuals who refused to take part in the study were close to those in the high risk group. The data obtained point to the possibility of defecting by means of preventive study individuals exposed to a greater or lesser risk of the development of ischemic heart disease and death, which makes it possible for the Public Health Service to concentrate attention of definite groups of the population so as to apply differentiated preventive measures.


[Arteriosclerosis of the aorta and coronary arteries in persons older than 70 living in different geographical areas of the USSR].

Visual-planimetric examination of the conspicuousness of atherosclerosis in the aorta and coronary arteries of persons who had died at an age of over 70 years was conducted in Tallin, Riga, Ryazan, Kharkov, Yalta, Frunze, and Ashkhabad (1,775 females and 1,425 males). The material was collected and studied according to the program elaborated by WHO experts for epidermilogic study of atherosclerosis according to post-mortem findings. It was found that atherosclerosis progresses at a much slower rate in persons over 70 than in those of younger age groups. The average conspicuousness of atherosclerosis in the vessels of females over 70 and particularly over 80 years of age often surpassed that in males. The least changes in the aorta and coronary arteries were found among the native population of Frunze and Ashkhabad and the most marked among natives of Tallin, Riga, Kharkov, and Yalta.


[Combined disorders of the central and regional hemodynamics and microcirculation in myocardial infarct].

Central and regional hemodynamics was studied in 228 patients with acute myocardial infarction by a complex of radio-indication tests. It was established that the degree of changes in central hemodynamics correlates to a definite extent with the severity of myocardial involvement (size of the damaged zone). Regional hemodynamics did not always change parallel to the reduction in cardiac output. The character of circulation in the organs of patients with myocardial infarction depends greatly on the internal control factors and the degree of tonic tension of the regional vessels. Changes in the regional circulation in myocardial infarction lead to hypoxia of the organ and severe disturbances in its function. In most patients the intraorganic hemodynamics decrease gradient was 11/2-2 times more than the cardiac output reduction gradient. Hemodynamic changes in myocardial infarction at the level of different vessels are of a multicomponent and non-linear character. The extent and rate of restoration of intra-organic hemodynamics are greatly determined by the severity of myocardial infraction and the presence of complications.


[Diabetes mellitus and cardiovascular system diseases in middle age].

The data on the interrelationship of diabetes mellitus and atherosclerosis are shown. To characterize the frequency of cardiovascular lesions and their different character according to age in patients with diabetes, the results of clinical analysis of 2,540 patients and the findings of thorough clinical and laboratory examination of 1,154 individuals, 20.1% of whom were over 60, are presented. The high frequency of angiopathies (84.6%) confirms the "atherogenics" effect of diabetes mellitus. The age differences consist in the predominance of organic lesions among elderly persons. The frequent occurrence of a disturbed glucose tolerance test and the development of diabetes mellitus in these patients are evidence of the "diabetogenic" effect of atherosclerosis. Some hormonal and metabolic mechanisms are investigated for the interpretation of the pathogenesis of cardiovascular lesions in diabetes. The contribution of contrainsular hormones (somatotrophic hormone, adrenal hormones) and hyperlipidemia to the development of diabetic angiopathies is substantiated. The difference between diabetic macroangiopathies and atherosclerosis in nondiabetic individuals is discussed on the strength of the results of electron microscopy of the mucle capillaries. It is concluded that these two diseases, which are widely encountered among elderly individuals, have hormonal, metabolic, and genetic developmental mechanisms in common.


[Basic problems of surgery in vascular atherosclerosis].

The author's opinion on the classification of atherosclerotic lesions of vessels is discussed and the peculiarities of the clinical picture, diagnosis, and surgical intervention in different localization of the lesions are analysed. An account is given of the basic propositions and principles of surgical management in atherosclerosis of the main localizations (aorta, brachiocephalic trunk, renal, mesenteric and other arteries). Sixteen-year experience in the surgical treatment of atherosclerotic vascular lesions is summarized. It is stressed that the results of reconstructive vascular operations, which were studied by the actuarial method, were good and permanent.


[Comparison of the echocardiographic indices of myocardial contractility and of the results of a bicycle ergometer test in chronic ischemic heart disease].

On comparing the results of study of the cardiohemodynamics indices under conditions of submaximum or threshold bicycle-ergometry load with the findings of echocardiography at rest in 64 patients with chronic ischemic heart disease, the authors conclude that echocardiography is a very promising method for ascertaining the cardiac muscular reserve, particularly in those patients with ischemic heart disease in whom the low coronary reserve does not allow the performance of tests under conditions of physical exertion.


[Code for evaluating the results of a physical load electrocardiographic test].

To standardize the evaluation of the results of the test with muscular exertion and make the findings of tests conducted in different laboratories comparable a universal code has been elaborated. With its use all abnormal, threshold, and some of the most important physiologic changes in the ECG as well as the principal clinical indices of the test with exertion may be fully described.


[Problems of the surgical treatment of congenital heart defects in adult patients].

A total of 175 adult patients with congenital heart diseases were investigated, of whom 140 were operated upon and 62 examined late after surgery. As noted, characteristic of adult patients were subjective complains, progressive pulmonary hypertension in defects with the blood shunting from the left to right and, because of this, the emergence of atypical symptoms of the defects. Surgical correction yields quite satisfactory results, but the presence of pulmonary hypertension tends to greatly increase the operative risk.


[Late results of the surgical treatment of interventricular septal defects].

The work deals with the following three problems: the criteria for the appraisal of the remote results; the evolution of pulmonary hypertension following correction of the defect; the indications for a repeated operation in reshunting. The examination was conducted on a group of 132 patients in postoperative periods of up to 13 years (5 years on the average) who had undergon surgery at the age of over 3 years. The analysis shows that the findings of clinical, electro-, phonocardiographic and X-ray examination are only of auxilliary importance as the criteria for the evaluation of the remote results. Changes in hemodynamics in remote periods after closure of the defect are the main indices of the efficacy of surgical management of patients with high pulmonary hypertension; it is just these changes that determine the prognosis. Considerable improvement in hemodynamics is revealed in most patients, which attests to the efficacy of surgery. In 29.2% of patients of the older age groups, however, mild or severe affection of the vessels of the pulmonary circulation was discovered. These data are an important argument in favour of early radical correction of the defect. In partial reshunting on the background of considerable improvement in hemodynamics and the general condition of the patient, one may refrain from carrying out an operation again and continue dynamik observation of the patient.


[Clinical anatomical basis of the pathogenesis of fatal complications in the late periods after heart valve prosthesis].

On the basis of clinico-anatomical analysis of the causes of death in 35 patients following valve prosthetics for rheumatic valvular disease, it was established that cardiac failure was the most frequent cause. Cardiac failure was due to exacerbation of the carditis process on the one hand, and to disorders of the rhythm induced by dystrophy, sclerosis, fibroelastosis, and calcinosis in the cardiac septum on the other. Thromboembolic processes rate second in frequency among the lethal complications. Death from septic complications was rarely encountered, and from causal causes only in individual cases.


[Defect in the interventricular septum in adults and the indications for its operative treatment].

The author had in his charge 76 patients over 16 years of age. In adults the congenital ventricular septal defect is of a relatively rare occurrence. The extent of the defect is largely determined by the evolution of the disease. In adult patients with minor defects there is no evidence of developing pulmonary hypertension, whereas in those with major defects in evidence is usually a well-marked hypertension. Surgery is indicated in patients with pulmonary hypertension of the I group exhibiting subjective symptoms and ECG and roentgenographic changes. Patients with pulmonary hypertension of the II-IIIa groups are also liable to undergo surgery, but here a relative contraindication is circulatory disturbance in the IIb stage.


[Electrocardiologic diagnosis and the prognostic significance of blocks occurring in ischemic heart disease].

A total of 280 patients with postinfarction and atherosclerotic cardiosclerosis and the bundle of His block were examined. The examination included recording of the ECG in 12 leads, the vectorcardiogram in the orthogonal system and after Frank and by the cube method, the cinecardiogram, polycardiogram, and radiocardiogram. It was established that bifascicular blocks of the left branch of the bundle of His are most unfavourable as regards the prognosis. The other types of blocks have no such effect and may rather be diagnostic signs indicating the localization and the extent of development of the necrotic or sclerotic process.


[Optimal frequency for electrical stimulation of the heart in transverse block in acute myocardial infarct].

Study of hemodynamics did not disclose any sole criterion for determining the optimum frequency of electric stimulation of the heart in the IV degree atrioventricular block in patients with acute myocardial infarction. Only a complex of indices serves the purpose, among which the first and foremost is the patient's general condition appraised by means of the routine physical methods and, whenever possible, by measuring the cardiac minute volume and the central venous pressure. The necessary frequency of electric stimulation in the prevention of arrhythmia should be chosen empirically.


[Scanographic picture of the lungs in acute myocardial infarct].

Lung scanning with MAA-131I was used to detect early "subclinical" stages of cardiac insufficiency in 51 patients suffering from primary myocardial infarction with different extent of involvement of the heart muscle. The contribution to the blood flow of the right lung was found to be rather greater than that of the left lung, and the contribution of the upper parts of the lungs greater than that of the lower parts. It was eatablished that the severity and stability of changes in pulmonary blood flow were in accordance with the extent of left ventricular involvement. The diagnostic value of MAA-131I scanning in identifying early stages of cardiac insufficiency and reorganization of pulmonary blood flow in patients with myocardial infarction for the choice of rational therapy and for prognostication is shown.


[State of the peri-infarct and necrotic areas in various complications of myocardial infarct according to ECG data (35 precordial leads)].

On the basis of ECG recorded in 35 precordial leads and subsequent cartographic analysis of the results obtained, the state of the necrotic and periinfarction zones in 38 patients with complicated myocardial infarction (development of circulatory insufficiency, acute aneurysm of the left ventricle, and pericarditis epistenocardica) was analysed. In circulatory insufficiency being the only complication, significantly smaller values of the indices characterizing the necrotic and periinfarction zones were found. In pericarditis, dynamics of the most mobile ECG indices was observed which characterized the state of the periinfarction zone in the direction of diminution (by half) by the end of the 1st week; in aneurysm the same degree of diminution was noted only by the end of the 2nd week of the process. In fatal outcomes of the disease these indices fluctuated within the range of the individual levels of the initial values without showing any obvious tendency to decrease in the first 2 weeks of the disease.


[Prerequisites for the physical training of patients who have had a myocardial infarct (substantiation, functional diagnosis, indications, contraindications)].

The substantiation and the indications and contraindications for the physical training of patients who have had myocardial infarction are discussed on the basis of the experience gained at the Clinic of Internal Diseases of the Medical Department of K. Marx University in Leipzig (DDR) and the First Chair of Hospital Therapy of the N.I. Pirogov Second Moscow Medical Institute. On the strength of their own findings and the information in the current literature, the authors name, among other precoditions for training, diminution of capacity for muscular work, psychologic instability and the persisting threat of the progression of ischemic heart disease. The methods of functional diagnosis, which is also a necessary precondition for the physical rehabilitation of the patients are bicycle ergometry, auxiliary tests for the gaseous composition of blood and exhaled air, determination of the heart volume by means of X-ray, catheterization of the pulmonary artery with a floating catheter, ventriculography, and coronarography.


[Mechanism of the prophylactic effect of adaptation to altitude hypoxia on the development of hypertension].

It was shown in experiments on 200 albino rats that prolonged adaptation to the periodical effect of hypoxia in an altitude chamber always resulted in partial atrophy of the adrenal glomerular zone and decrease in the synthesis of mineralocorticoids in the adrenals and in their concentration in blood. At the same time, the size of the supraoptic hypothalamic nuclei and their cytogically determined activity diminished. These structurally fixed adaptational changes in the hormonal control caused a stable decrease in the reseves of sodium and water in the organism of the adapted animals. This complex of shifts is contrary to the changes developing in all forms of experimental hypertension and in hypertensive disease in humans. The idea is discussed that inhibition of mineralocorticoid and ACTH secretion and the stable decrease in the sodium and water reserves in the organism during adaptation play the principal role in the mechanism of the preventive effect of adaption to altitude hypoxia in hypertension.


[Effect of hexahydroubiquinone-4 (KoQ4) on the bioenergetics and functional activity of the myocardium in ischemia].

The effect of KoQ4 on the energetics, contractility, and electrogram of the ischemized myocardium was studied in acute experiments on dogs with induced myocardial ischemia. Intracornoary administration of KoQ4, 1.3 mg/kg, directly into the focus of ischemia for 15 min promoted a decrease in the lactate level in blood draining from the ischemic zone as compared to the control data in the absence of a difference in the dynamics of the pyruvic acid content. In distinction to the control experimental series, there was no decrease in the concentration of glucose in samples of venous blood draining from the focus of ischemia. Under the effect of KoQ4 the amplitude of left ventricular pressure and the maximum rate of its growth (dp/dt) increased moderately and the ST segment and ST/R coefficient of the epicardial electrogram from the border zone of ischemia decreased. It was shown in the rat experiments that preliminary intravenous administration of KoQ4 (14 mg/kg) increased myocardial resistance to oxygen deficiency under conditions of diacetylcholine-induced apnoe.


[Fibrinogen metabolism in congestive circulatory insufficiency].

Using 125I-labelled fibrinogen the metabolism of this protein was studied in 29 patients with II-III stage congestive circulatory insufficiency due to ischemic heart disease and rheumatic heart diseases. It was established that with the progression of circulatory insufficiency fibrinogen half-life increased. The body content of total fibrinogen increased with the gradual intensification of circulatory insufficiency due to growth of the extravascular (noncirculating) fraction. The growth is associated with the intensified egress of circulating fibrinogen into the extravascular space (thrombus, tissue, etc.). The role of disseminated intravascular clotting and consumption coagulopathy in the pathogenesis of congestive circulatory failure is discussed.


[Selection of groups of the male population 40 to 49 with risk factors for conducting primary prophylaxis of ischemic heart disease].

The method of selecting population groups with risk factors for applying measures of primary prevention of ischemic heart disease among males 40 to 49 years of age is discussed. The article shows the results of two-stage screening conducted among 18,707 males born between 1922 and 1931 for the selection of volunteers with relatively stable risk factors of ischemic heart disease: arterial hypertension (systolic pressure 160 mm Hg or higher and/or diastolic pressure 96 mm Hg or higher) and hypercholesterolemia (above 260 mg percent). The data of the experimental preventive study show a lack of willingness among the population to take part in preventive measures aimed at controlling ischemic heart disease. When conducting preventive measures  among the unorganized population, most attention should be focused on the organization of the primary screening examination, i.e. the first contact of the population with the physician.


Isolation and characterization of rat tubular basement membrane.

Tubules were isolated by the passage of coarsely homogenized kidney parenchyma through a series of stainless steel sieves of varying pore sizes. The isolated tubules, which were free of glomeruli or any contaminating tissue, based on light microscopic examination, served as starting material for the isolation of tubular basement membrane (TBM). The tubules were sonically disrupted, and the subsequent isolation procedure was conceptually similar to that of the isolation of glomerular basement membrane (GBM). The chemical composition of TBM was compared to that of GBM and collagen. 3-hydroxyproline, a marker for basement membrane protein, was present in higher amount in TBM (10 residues per 1,000 amino acid residues) than in GBM (7 residues per 1,000). Glycine and hydroxylysine content was also higher in TBM (255 and 27 residues per 1,000, respectively, in contrast to 204 and 18 residues in GBM). The total carbohydrate content was 7.6 mg per 100 mg of dry weight (neutral sugars, 6.3; GlcN, 0.9; GalN, 0.1; and sialic acid, 0.3). By electron microscopic examination, the isolated TBM was similar to GBM, except for greater variability in diameter and serrated appearance of one surface of the tubular basement membrane fragments. The method is suitable for the isolation of TBM in sufficient quantity for subsequent chemical analyses and immunologic studies.


Maleic acid-induced impaired conversion of 25(OH)D3 to 1,25(OH)2D3: implications for Fanconi's syndrome.

Conversion of 25-hydroxyvitamin D3 [25(OH)D3] to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] occurs exclusively in the renal cortex. To determine whether a disorder of the renal cortical tubule capable of causing Fanconi's syndrome can also impair the synthesis of 1,25(OH)2D3, we investigated whether conversion of 25(OH)D3 to 1,25(OH)2D3 was reduced by maleic acid. In vitamin D-deficient rats, maleic acid was administered i.v. over two hours. Thirty minutes after its initiation, when the complex renal tubule dysfunction had occurred, 3H-25(OH)D3 was administered i.v. as a bolus. Five hours afterwards, the amount of 3H-1,25(OH)2D3 recovered in the kidney, small intestine mucosa, and blood was one-third to one-half that in tissues of control rats that received acetazolamide or only saline or were subjected only to the surgical procedure. The glomerular filtration rate, as measured by inulin clearance, did not decrease significantly with maleic acid. In intact vitamin D-deficient chicks, 24 and 22 hr after i.p. administration of maleic acid and 14C-vitamin D3, respectively, the amount of 14C-1,25(OH)2D3 recovered in small intestine mucosa was reduced by one-half when compared to saline-treated controls. In kidney homogenates and isolated renal tubules of vitamin D-deficient chicks, activity of 25-hydroxyvitamin D3-1-hydroxylase was diminished immediately after maleic acid was administered in vivo or added in vitro to the incubation medium, respectively. These data provide the first demonstration that the renal capacity to convert 25(OH)D3 to 1,25(OH)2D3 can be substantially impaired in vivo by a renal disorder in which the glomerular filtration rate is not reduced.


Renal vascular response to interruption of the renin-angiotensin system in normal man.

We assessed the role of the renin-angiotensin system in the response of the renal circulation to restriction of sodium intake in 38 normal patients. Both saralasin (10 to 30 ng/kg/min), an angiotensin antagonist, and SQ 20881 (30 to 300microgram/kg), a converting enzyme inhibitor, induced a dose-related increase in renal blood flow (xenon 133 washout) only when the resin-angiotension system was activated by restriction of sodium intake to 10 MEq/day. Increasing doses of saralasin (100 to 1,000 ng/kg/min) reduced renal blood flow, presumably due to the angiotensin-like action of this partial agonist. The renal vascular response to SQ 20881 paralleled the endocrine response: An identical threshold dose (30 microgram/kg) increased renal blood flow and reduced plasma angiotensin II concentration, which fell despite a progressive rise of plasma renin activity. Plasma bradykinin concentration did not change in response to SQ 20881, which also blocks kininase II. Both agents also induced a small but consistent and statistically significant reduction in arterial blood pressure, which will be important in assessing the pathogenetic significance of a blood pressure reduction in patients with hypertension. This study indicates that angiotensin mediates the renal vascular response to restriction of salt intake in normal man and provides an approach to assessing the role played by angiotensin in the pathogenesis of functional renal disease.


Autonomic blockade and the Valsalva maneuver in patients on maintenance hemodialysis: a hemodynamic study.

Hemodynamic studies were performed at two levels of dietary sodium intake (10 mmoles/day and 100 mmoles/day for 14 days) in a group of patients (with retained kidneys) on chronic hemodialysis. Plasma renin activity and aldosterone, plasma, and extracellular fluid (ECF) volumes were measured while the patient were at rest. Cardiac output, mean intraarterial pressure, and the calculated total peripheral resistance index were recorded while the patients were at rest and during acute "total" autonomic blockade. On the sodium diet of 10 mmoles/day, normotensive and hypertensive patients had similarly low total blood volumes, low-normal ECF volumes, and similar levels of plasma renin and aldosterone. The resting cardiac output was increased in both groups, but the total peripheral resistance was increased only in the patients with hypertension, in whom peripheral resistance was inappropriately high for the degree of anemia. Six hypertensive patients were studied on both diets. The resting mean arterial pressure was greater on the sodium diet of 100 mmoles/day than on the 10 mmoles/day diet, accompanied by increased in plasma volume, extracellular fluid volume, and cardiac output, but no change in peripheral resistance. During autonomic blockade on either diet, there was a marked fall in blood pressure in the patients with hypertension. This was mainly due to a fall in peripheral resistance which reached levels similar to those seen in the normotensive patients whose resistance was unaltered by blockade. Autonomic factors appear to contribute to the elevated peripheral resistance of hypertensive dialysis patients. In these patients, the effect of a high sodium diet, at least over the time-scale studied here, is to increase blood pressure and cardiac output, without the change in peripheral resistance expected from autoregulation.


[Clinical results of the goniothrephining with scleral flap (author's transl)].

During 1971-1976 407 goniotrephinings e.g. "Elliot with scleral flap", were performed at the Univ. Eye Hospital Münster. In a follow-up study of 306 operated cases we found 81% primary glaucoma (62.7% simple glaucoma, 18.3% chronic congestive glaucoma) and 19% secondary glaucoma. In 77% of the operated cases the anterior chamber was restored within the first postoperative day. Gonioscopically in 85% the trephining hole was placed within the trabecular meshwork. Nevertheless, this position of the hole had no decisive influence on the later filtration. Postoperatively 2/3 of cases developed a characteristic flat filtering bleb. In 90.4% of the eyes the postoperative IOP was within normal limits. Postoperative follow-up of the visual acuity remained within the limits of age deterioration. Concerning the secondary glaucoma, the pigmentary glaucoma, the traumatic glaucoma and the glaucoma after uveitis, had good results. The results in cases of buphthalmos and hemorrhagic glaucoma were worse. The advantages of goniotrephining are the rapid restoring of the anterior chamber, the protection of the trephining hole by the scleral flap as well as the well "protected" flat and infections-resisting bleb.


[Investigations on the relationship between intraocular pressure and perifoveal capillary circulation in glaucoma patients using the entoptic blood corpuscle phenomenon (author's transl)].

Blood circulation in the central retina was examined in 30 eyes suffering from glaucoma, using the entoptic phenomenon to count leucocytes travelling through the retinal capillaries in the macula area. Two measurements were taken for each eye at different intraocular pressure levels and the results were compared with each other. They showed that reduction of an originally high intraocular tension level significantly increased the blood flow. In a control group of healthy eyes in a similar group of patients insignificant changes in blood flow were recorded. There was thus a direct linear relationship between reduction of intraocular pressure and relative increase in blood flow with a strongly positive correlation (r = 0,74). Hence an effective autoregulation of blood flow in relation to changes in intraocular pressure could not be demonstrated.


[Concentration of ampicillin in the vitreous after photocoagulation of the retina (author's transl)].

After photocoagulation of the retina a higher amount of ampicillin was found in the vitreous of the coagulated eyes, as our tests have shown. The reached concentrations of ampicillin were in the therapeutical region for sensitive germs. The highest concentration of ampicillin was reached when the ampicillin was injected in the edema stage of the coagulation effects. Therapeutical effective concentrations in the vitreous could be kept with this method up to five days after photocoagulation.


[Electro-ophthalmological findings in so-called partial "retinopathia pigmentosa" (author's transl)].

A description is given of bilateral, sectoral retinopathia pigmentosa in a female subject and her eldest son. The diagnosis is difficult without an ERG and EOG because of the paucity of symptoms. The disease is characterized by subnormal ERG potentials and a flat EOG curv. In questionable cases, periodic re-examinations and the examination of family members can be helpful.


[Retinopathy and angiopathy in diabetes of fifty to sixty years duration (author's transl)].

A report is given on ten (seven female, three male) diabetis with uncommonly long duration of the disease. Diabetes had become manifest at an early age (mostly childhood) and, then, had continued for a period of fifty to sixty-one years. Eight patients suffer from retinopathy, two are free from it. Only three cases show nephropathy of moderate development and inconspicuous progression. Coronary sclerosis, peripheral sclerosis, and neuropathy recede with time. There is a surprising discrepancy of findings concerning retinopathy - on the one hand: simple retinopathy tending to spontaneous regression; on the other hand: malignant proliferating retinopathy. Uncommon also is the tarrying behaviour of nephropathy.


[Ocular myopathy with giant mitochondriae (author's transl)].

A case of progressive external ophthalmoplegia and a slight coincident affection of the scapulohumeral muscle group is recorded. Thorough examination including EMG and biopsy from ocular and skeletal muscle tissue confirmed the clinical diagnosis of myopathy. By means of electron microscopy the affection could be identified as a type of myopathy characterized by giant mitochondriae. Causative factors were not detectable. The function of the thyroid and the carnitine level in the muscle tissue and blood serum were normal.


[Unrecognized paralyses of accommodation and their importance in diagnostics and expertise (author's transl)].

Paralyses of accommodation are safely diagnosticizable even in patients over 45 years of age provided there is no complete presbyopia. The identification can be a key to diagnosing the entire disease pattern. In one case a suspected Adie's syndrome with amblyopia and without any connection with internment and damage due to malnutrition was identified as ophthalmoplegia interna with partial atrophy of the n. opticus, most probably caused by malnutrition encephalopathy or encephalitis. In another patient, a bilateral isolated accommodation paralysis indicated damage of the accommodation center during concussion of the brain (possibly only a functional damage).


[Use of an automatic laboratory rinsing machine for cleaning and disinfection of ophthalmosurgical instruments (author's transl)].

A report is given on the use of an automatic rinsing machine for the cleaning of surgical eye instruments combining the processes of disinfection, cleaning and drying in one operation and thus providing good protection against corrosion and optimal protective treatment of the cutting blades. To allow use in ophthalmology, a special insert was constructed.


[Idiopathic edema, capillaropathy, pericardial and pleural effusions with high protein content (author's transl)].

Clinical and electron microscopic studies of two female patients are reported who, in addition to the symptoms and signs of idiopathic edema, had pericardial (and pleural) effusions. In one patient pericardiectomy had to be performed, in the other patient pharmacotherapy with spironolactone was effective. In these patients the protein-concentrations of edema fluid (25 and 12 g/l) and pericardial fluid (55-61 and 48 g/l) were relatively high; the distribution space of labelled protein was increased; blood volumes were low-normal or decreased. Electronmicroscopy of the microvasculature showed identical alterations in both cases. In the cutaneous vessels the endothelium developed numerous abnormal cytoplasmic processes and intercellular "gaps". In the capillaries of skeletal muscle our findings indicate an increase in vesicular transport. We suggest the electron microscopic alterations to be the morphologic correlate for the increased transport and extravascular accumulation of protein. Changes as they are described here in humans with idiopathic edema have been documented before in animals with experimental edema.


[Distribution of haemoglobin content in human red cells, estimated by scanning cytophotometry (author's transl)].

Haemoglobin content and surface area of human red cells were estimated using a scanning cytophotometer connected to a computer for registration and analysis of the data. The measurements were carried out on fixed, unstained peripheral blood smears at a wavelength of 414 nm. The scanning can be controlled on the screen in order to detect errors and to eliminate extinctions from other sources than the cell examined. The method allows to demonstrate the topographic quantitative distribution of haemoglobin within the cell, to estimate haemoglobin content and surface area in individual cells and to correlate these values, to establish frequency distributions of the data within cell populations and to calculate various statistical parameters. Results of measurements on normal and abnormal red cells (iron deficiency, haemolytic anaemias) are demonstrated. The method may be used for investigation on red cell pathophysiology and may serve as a basis for image analysis in blood smears. It is too time consuming for direct diagnostic application in clinical practice.


[The effect of antrectomy or total gastrectomy on calcium-induced gastrin secretion and gastrin release in man (author's transl)].

The effect of induced hypercalcemia on serum gastrin concentrations, measured by radioimmunoassay, and gastric acid secretion was studied in 20 healthy subjects, 8 patients after antrectomy and gastroduodenostomy (Billroth I), 12 patients after antrectomy and gastrojejunostomy (Billroth II) and in 9 patients after total gastrectomy and esophagojejunostomy. In normal man calcium stimulates gastric secretion and gastrin release. After antrectomy gastric secretion is still stimulated by calcium without changing serum gastrin levels. After total gastrectomy basal serum gastrin concentration is further reduced; calcium does not liberate gastrin. These results show that calcium-induced gastric secretion is caused by direct action at the parietal cell level besides the gastrin release from the antrum. In man, extra antral gastrin cannot be released by induced hypercalcemia.


[Ascorbic acid content in plasma and in leukocytes in patients undergoing maintenance haemodialysis (author's transl)].

Patients undergoing maintenance haemodialysis exhibited at a regular level of ascorbic acid in plasma a decreased concentration of ascorbic acid in leukocytes. Therefore, the ascorbic acid should be administered in a high dosage to patients undergoing chronic haemodialysis, in order to prevent a vitamin-C deficiency in leukocytes.


Behavior and maintenance of the woolly opossum (Caluromys) in captivity.

Circadian activity, general behavior, dietary requirements, and reproductive activity were recorded in a small laboratory colony (four females, six males) of two species of the woolly opossum (Caluromys lanatus and C derbianus) over a period of 3 years. The two species were indiscernable in all aspects of their behavior. Both were completely nocturnal and rarely active during daylight hours. General behavior was apparently related to many variables, particularly individual temperament and cage size. Even docile individuals were more excitable when housed in small cages. Although the woolly opossum is reported to prefer a meat diet, the opossums in this study remained healthy on a meat-egg-fruit diet, and showed a special liking for fruit, especially bananas. Vaginal smears indicated that females of the colony were cyclic, but all attempts to breed them were unsuccessful. Sexual behavior included pre-mount, pelvic-thrust displays on the part of the male, with complete repulsion by all females.


Successful pregnancies with concentrated frozen canine semen.

A method for concentrating canine semen prior to freezing was developed. Concentration was by centrifugation at 1470 g at room temperature, after which the majority of seminal fluid was removed. Motility, speed of progression, and morphology of sperm were not affected by concentration. Subsequent artificial insemination using concentrated semen resulted in a conception rate of 92%. The offspring were normal and healthy. The mean litter size (6.7) and birth weight (256.3 g) were comparable to those reported by a commercial supplier (6.2 and 255.7 g) of the same breed (beagle).


Apparatus for controlling temperature of catheter contents in cold environments.

An apparatus was developed to prevent the freezing of catheter contents during blood sampling or liquid infusion into animals maintained at sub-freezing temperatures. The apparatus consisted of a larger, outer set of plastic and copper tubes and a smaller, inner set of tubes. The catheter was passed inside the inner set. Water circulated through the outer set kept the contents of the catheter inside the inner set from freezing. The apparatus was also useful for the rapid cooling of blood to a predetermined temperature while a sample was being withdrawn from an animal.


Dietary, bacterial, and host genetic interactions in the pathogenesis of transmissible murine colonic hyperplasia.

Transmissible murine colonic hyperplasia, cuased by a variant of Citrobacter freundii (4280). was shown to be modified by diet and by host strain and species. Four different diets fed to mice inoculated with C frundii 4280 were found to have a significant but varying influence on the severity of hyperplasia. Diet also influenced the colonic crypt height of uninoculated, control mice. F344 rats, Syrian hamsters, and NIH Swiss [N:(S)], C57BL/6J, C3H/HeJ, and DBA/2J mice were inoculated with C freundii 4280. Marked strain differences were noted in the mice in mortality and severity of the colonic hyperplasia. The NIH Swiss mice had the greatest and the C57BL/6J mice had the least mucosal hyperplasia. The rats and hamsters did not develop disease or maintain infection after inoculation with the organism. Twenty isolates of Citrobacter from a range of biologic sources were inoculated into susceptible mice, but only mice inoculated with C freundii 4280 developed the disease.


Secondary effects of aganglionosis in the piebald-lethal mouse model of Hirschsprung's disease.

An attempt was made to identify the factors secondary to fecal stasis and megacolon that are related to overall debilitation and eventual death of the piebald mouse. The piebald mouse showed periodic leukocytosis and bacteremia that were associated with lesions in the mucosal surface of the megacolon. Defective growth, loss of weight, and retardation of development with megacolon were documented by systematic study of body weight and of the relationship between body weight and organ weights. Alterations in body weight and in organ weight to body weight ratios were parallel in the piebald mouse, in mice with imperforate anus, and in mice with surgically-induced megacolon. Histologic studies confirmed a pattern of hypertrophy of the muscularis externa in the piebald mouse. The body temperature was lower than for normal siblings, but the sodium, potassium, and water content of the feces, the general blood chemistry profiles, and the intestinal microflora did not differ from those of the normal mouse. There was no evidence of bacterial overgrowth in the small intestine of the piebald mouse with fecal stasis and megacolon.


Variations of sodium, potassium, and chloride plasma levels in the rat with age and sex.

Sodium, potassium, and chloride plasma levels were measured in 294 male and 286 female Sprague Dawley rats [Crl:COBS CD(SD)BR]. The rats were distributed between four groups according to age (65-125 days, 235-275 days, 353-482 days, and 665-775 days). The levels of all three ions were higher in males than in females: about 1% higher for sodium and chloride and about 7% higher for potassium. Potassium and chloride values decreased with increasing age in both sexes; potassium decreased 12% and chloride decreased 6%. Distributions were not perfectly Gaussian but the departures from normality were slight. It was concluded, therefore, that determinations based on parametric statistical tests on the data are unlikely to be seriously biased by the distribution.


Serum chemistry values of normal dogs (beagles): associations with age, sex, and family line.

One hundred and sixteen colony control dogs (purebred beagles) ranging in age from 56 to 4868 days at the time of sampling, were tested at various intervals over a 10-year period to determine the normal values of several serum constituents. The effects of sex and family line were also noted. With increasing age, serum glutamic-pyruvic transaminase, total protein, and cholesterol increased, whereas glucose, serum glutamic-oxalacetic transaminase, creatine phosphokinase, iron, alkaline phosphatase, and albumin decreased. Females had significantly higher levles of urea nitrogen, iron, and cholesterol than males. Males had significantly higher serum glutamic-pyruvic transaminase levels. The rate of increase in serum cholesterol with age was greater in males than in females. Males showed no age related changes in levels of urea nitrogen or iron, while the females showed decreasing levels. Significant differences in total protein and albumin were noted in dogs belonging to different family.


Chronic double lumen intravenous cannulation of the unrestrained rat.

Chronic double lumen intravenous cannulation was performed on the rat. The cannulation system consisted of a pulley assembly, protective tube, mounting post, and a double lumen cannula. Using a double lumen expanded catheter, a two-channel connection was made with the rat's vascular system through a single entry into the external jugular vein. The cannulation system permitted free animal movement in a large cage and simultaneous measurement of behavioral and physiologic variables. The procedure minimized stress and provided a simple alternative to other systems using two cannulas.


Scanning electron microscopy of guinea pig alveolar macrophages: in vitro phagocytosis of Mycoplasma pneumoniae.

The scanning electron microscopic appearance of guinea pig alveolar macrophages during in vitro antibody-mediated phagocytosis of Mycoplasma pneumoniae is described. This study utilizes the ability of M. pneumoniae to attach to and replicate on a glass cover slip surrounding a monolayer of macrophages without inducing phagocytosis despite multiple points of interaction between organisms and macrophage filopodia. The addition of specific anti-M. pneumoniae serum to this system evokes a sequence of macrophage surface morphologic changes accompanied by engulfment of the surrounding mycoplasmas. The sequence of changes occurring over the 90 minutes subsequent to the addition of antiserum were visualized well with the scanning electron microscope and included the early appearance of elongated, rigid filopodia, the internalization of M. pneumoniae by ruffled membrane extensions, and finally the appearance of highly spread cells surrounded by large areas of cover slip cleared of M. pneumoniae.


The role of inflammatory cells in the pathogenesis of amyloidosis.

In the presence of amyloid enhancing factor, a variety of inflammatory stimuli, many of them nonantigenic, trigger amyloid deposition in 48 hours. There is a striking correlation between the extent of splenic amyloid deposition and the severity of inflammation at the injection site of the various irritants. Sublethal irradiation results in a parallel effect on the local inflammatory response and the accompanying extent of amyloid deposition produced in the spleen. Evidence that a product of local acute inflammatory responses is related to the deposition of amyloid is also presented. It is proposed that this product is a protease derived from the infiltrating polymorphonuclear leukocytes.


An electron microscopic study of intraepithelial lymphocytes in human fetal small intestine.

Human small intestine was obtained from fetuses at 8 to 20 weeks of gestation. The tissues were examined by electron microscopy. Lymphocytes were present as isolated cells in the mucosal mesenchyme as early as the 8th week of intrauterine life and were found, in increasing numbers, in the epithelium of specimens obtained from 11- to 20-week-old fetuses. All intraepithelial lymphocytes were located in the lateral spaces between contiguous columnar cells. Some displayed cytoplasmic pseudopods and were thought to migrate within the extracellular spaces of the epithelial layer. Surface invaginations and cytoplasmic vesicles in fetal lymphocytes suggested that these cells were capable of pinocytotic activity. The possibile origin and function of lymphocytes in fetal small intestine are discussed.


Correlative scanning and transmission electron microscopy of glomeruli.

Scanning electron microscopy was performed on 125 human renal specimens and control rat kidneys in conjunction with light microscopy and transmission electron microscopy. Specimens were prepared by glomerular isolation, free hand slicing, alcohol cryofracture, and polyethylene glycol embedding and ultraplaning. Heavy metal secondary electron sources on the tissues were produced by osmic acid, thiocarbohydrazide, osmic acid treatment (O-T-O) followed by gold-palladium coating, or by staining with uranyl acetate and lead citrate. Critical point drying was used uniformly. Useful observations of normal rat glomeruli were made. In the study of diseased human glomeruli, podocyte changes were classed as cytoplasmic projection, foot process changes, and changes of necrosis or basement membrane denudation. Artificial lesions of compression and contamination were defined. Cryofractured and ultraplaned stained specimens were very useful for studying diseased tissues. These methods offer the opportunity to increase our conceptual and diagnostic understanding of glomerular disease.


An electron microscopic study of hepatic erythropoiesis in adult mice with Friend virus disease.

A polycythemia-inducing strain of Friend virus was injected into adult mice. Animals were sacrificed on days 2, 5, 9, 11, and 14, and specimens of liver were fixed and embedded for light and electron microscopy. From some mice, samples of bone marrow and spleen were also processed for microscopy. Hepatic erythropoiesis was established as early as 2 to 5 days after inoculation. Often, red cell maturation occurred in typical islands. These included a central macrophage which in many instances appeared to be a Kupffer cell. The number and size of red cell foci increased through day 14. Extensive ineffective erythropoiesis involving erythroblast death occurred within these foci. This premature cell death may be related to large inclusions, thought to be autophagosomes, in the cytoplasm of erythroblasts. A few undifferentiated cells, presumed to be the reticulum cells of Friend virus disease, were observed in the liver at 9 to 14 days after infection. The morphology of these cells resembled that of primitive hemopoietic elements. These studies indicate that the liver, along with the spleen, contributes to the polycythemia in the early phase of Friend virus disease.


Lipolytic activity of human lingual glands (Ebner).

Human tongue preparations contain lipolytic activity similar to that present in human esophageal and gastric aspirates and in serous glands of rat tongue. The activity is present in homogenates of the glandular region (Ebner) beneath the cirumvallate papillae, and in secretions collected from the trough of the papillae. The lipolytic enzyme hydrolyzes long chain triglycerides to partial glycerides (di- and monoglyceride), glycerol, and free fatty acids at pH optimum 5.4. Lipolytic activity, expressed as nanomoles of triglyceride hydrolyzed per minute was in the range of 0 to 500 per gm. of tongue homogenate and 78 to 277 per ml. of aspirate from the vallate papillae. There was a 50% inhibition of the lipolytic activity by 4 mM sodium taurodeoxycholate. Specimens obtained from the region of the vallate papillae were examined by light and electron microscopy. Electron-dense granules similar to secretory granules present in rat Ebner's gland and in serous acini of human submaxillary glands were detected. Our findings suggest that in man, as previously reported in the rat, the lingual serous glands secrete a lipase that acts in the stomach where it initiates the digestion of dietary fat.


Studies related to the head-maturation pathway of bacteriophages T4 and T2:I. morphology and kinetics of intracellular particles produced by mutants in the maturation genes.

Mutants in the genes governing the maturation of the head of bacteriophage T4 and in gene 24 were studied by electron microscopy of thin sections. We define morphologically: black particles, comprising mature, stable heads and immature, fragile heads, which break down upon lysis; grizzled particles, which apparently are partially filled or partially emptied; empty large particles without DNA or core which are all the same size as normal heads; empty small particles without DNA and without core which are of the size of the tau particle, which is the prehead of phage T4. The study of single and double mutants of the maturation genes demonstrates that the phenotypes are only different by the proportions of the different particles made except for 17- where only empty small and empty large particles accumulate. The mutants in gene 24 are epistatic on all other mutants. Mutants in gene 17 are epistatic on the remaining ones. The results are consistent with the hypothesis that the products of several of the maturation genes act on DNA to render it competent for packaging while the others act directly on the particle. By this uncoupling, bypasses and abortive pathways can result.


Studies related to the head-maturation pathway of bacteriophages T4 And T2:II. nuclear disruption, protein synthesis and particle formation with the mutant 43-.30-.46-.

We describe the aberrant phage multiplication of the triple conditional lethal mutant 43-(polymerase).30-(ligase).46-(exonuclease) of bacteriophage T4D in which phage DNA replication is arrested but some late protein synthesis occurs (33). The nuclear disruption is indistinguishable from wild type. Forty-five empty small and empty large particles are assembled per cell when the multiplicity of infection (m.o.i.) is 100. This number corresponds closely to the 38 phage equivalents of cleaved major head protein determined biochemically. By reducing the m.o.i. the number of observable particles decreases, reaching 1-5 per cell at an m.o.i. of 5(+5). The total synthesis of phage related proteins is not significantly dependant on the m.o.i. The synthesis of late proteins is about 10% of that of wild type at high m.o.i. and decreases with the m.o.i. The different early and late proteins do not show the same relative proportions as in wild type and respond differently to an increased m.o.i. These and other results are discussed with respect to the role of phage DNA in prehead assembly and head maturation.


Effect of calcium on the pellet height response of Tetrahymena cilia.

The pellet height response (a measure of the increase in height of the pellet of cilia obtained by brief centrifugation in the presence of ATP as compared to the absence of ATP) of Tetrahymena cilia prepared by deciliation in the presence of Ca2+ is sensitive to the concentration of free Ca2+ during the pellet height assay. The magnitude of the increase in pellet height and the sharpness of the pellet boundary both increase markedly with increasing [Ca2+]. The half-maximal effect is attained at a free [Ca2+] of about 1.5 x 10(-7) M. The pellet height assay thus measures a Ca2+-sensitive component of the ciliary motile system. The possibility that this is the Ca2+-sensitive orientation system is discussed.


Biochemical characteristics, metabolism, and antitumor activity of several acetylated hexosamines.

We have synthesized several potential inhibitors and/or modifiers of the carbohydrate portion of plasma membrane glycoconjugates. These include fluorinated and actylated analogs of D-glucosamine, D-galactosamine, and D-mannosamine. These compounds have been tested to determine their effects on both[14C] glucosamine and [3H] leucine incorporation into glycoconjugate and on cell growth and viability using P-288 murine lymphoma cells maintained in tissue culture. The most cytotoxic agent tested was 2-acetamido-2-deoxy-1,3,4,6-tetra-O-acetyl-beta-D-glucopyranose or simply beta-pentaacetylglucosamine which prevented cell growth at 10(-4)-10(-3) M. beta-Pentaacetylglucosamine cytotoxicity was correlated with its high lipid solubility, having an octanol/water partition coefficient of 0.424 as compared with 0.278 for the alpha-anomer and 0.017 for N-acetylglucosamine. In vitro metabolism studies with [4C]- and/or [3H]-labeled pentaacetylglucosamine have indicated intracellular de-O-acetylation leading to the biosynthesis of UDP-N-acetylglucosamine, followed by the incorporation of this sugar into cellular glycoprotein. Concomitant with the formation of increased amounts of this nucleotide sugar, intracellular UTP and CTP pools fell to one third normal within 3 h after the administration of 1 mM pentaacetylglucosamine. At present it is unclear whether the cytotoxicity of beta-pentaacetylglucosamine or other similar agents is due to alterations in nucleotide and nucleotide-sugar pools causing a decrease in energy charge and polynucleotide biosynthesis or is due to a direct effect on membrane glycoconjugate biosynthesis.


Possible involvement of GABA mechanisms in central cardiovascular and respiratory control. Studies on the interaction between diazepam, picrotoxin and clonidine.

Various doses (0.1-1 mg/kg) of diazepam were given to chloralose anesthetized rats, with both systemic (i.p.) and central injections being tested. Arterial pressure, heart rate, respiration depth and frequency were recorded. Diazepam caused a dose-dependent decrease in the arterial pressure after systemic administration and also decreased it after central administration. However, only intraventricular but not intracisternal injections of diazepam were effective. The hypotensive effect of systemic diazepam was competitively counteracted by pretreatment with picrotoxin, a putative gamma-aminobutyric acid receptor blocking agent. The hypotensive effect of the centrally acting alpha-adrenoreceptor agonist clonidine was not influenced by picrotoxin pretreatment. The effect of diazepam on heart rate was inconsistent. Diazepam caused a reduction of respiratory frequency, which was not counteracted by picrotoxin pretreatment. It is concluded that central gabergic mechanisms are to some extent involved in the hypotensive effect of diazepam, probably at a supramedullary level. The hypotensive effect of a threshold dose of diazepam was blocked by a small dose of clonidine. Likewise, diazepam pretreatment could counteract the hypotension, bradycardia and respiratory frequency reduction caused by a threshold dose of clonidine. These results suggest that gabergic and/or other benzodiazepine-sensitive receptors may interact with alpha-adrenoreceptors in the control of central cardiovascular and respiratory mechanisms.