[Development of heart innervation in Xenopux tadpole and relationship with organ function]. Cardial innervation is studied through specific techniques. It is set up in 9 to 18 mm tadpoles. The rhythm of the aneural heart progressively increases. The initial automatic working is of ventricular type. The ventricular action potential acquires its typical form after the establishment of innervation. At the same time, cardial rhythm settles down at 110 beatings/minute.


[Effect of exogenous progesterone on 17 beta estradiol secretion in 4-day cyclic rats]. The rate of ovarian 17 beta oestradiol was showed to be decreased on the decreased on the afternoon of dioestrus 2 in 4-day cyclic female rats with cycles prolonged to 5 days following progesterone treatment as compared to untreated 4-day cyclic females. OEstradiol values also appeared lower on dioestrus 3 and prooestrus in experimental 5-day cycles than, on prooestrus, in natural 4-day cycles.


[Teratospermia and migration of spermatozoa in vitro and in vivo]. The comparative study of morphological anomalies of spermatozoon before and after penetration shows that in vivo or in vitro migration causes a selection of the spermatozoon. This selection is not complete. Anomalies of the midpiece or of the flagella inhibe the spermatozoon progression but morphological anomalies of the head are not a handicap for the migration. this observation seems to indicate that spermatozoa with chromosomic failures can paticipate to the fertilization.


[Sulfurtransferase activity in cultured neuronal clone cells]. The activity of 3'-phosphoadenosine-5'-phosphosulfate : galactocerebroside sulphotransferase (PAPS - CST, EC 2.8.2.11), which catalyzes the synthesis of sulphatides, was measured in cloned cells (NIE 115) derived from mouse neuroblastoma C-1300. This activity was of the same order of magnitude as that observed in adult mouse brain. The cell density had no effect on the specific activity of the PAPS-CST.


[Effect of various inhibitors on oxidative activity and ultrastructure of rat liver mitochondria]. Parallel studies concerning the influence of some inhibitors on electron transfer, and ultrastructural aspects of rat liver mitochondria led to the conclusion that metabolic activity and mitochondrial ultrastructure are closely linked ; when mitochondria oxidize succinate, their configuration change from the "condensed" to the "orthodox" state ; this change does not occur if the oxidation is inhibited.


[Mechanism of glucose oxidation by a Pseudomonas fluorescens strain (type R). III. Influence of endogenous non-protein factors]. Cells of P. fluorescens cultivated in iron-deficient media contain two types of constituents, one of which can activate and the other reduce the rate of oxidation of glucose and of the endogenous substrates. These factors, which are of non-protein nature, have been distinguished and characterized by their physiological activity on non-proliferating cells suspensions of these bacteria.


[Spleen enhancement reactions in chick embryo after homografting adult chicken spleen fragments: changes in spleen cell population in relation to rate of spleen enhancement]. A method using the comparison between the modifications of spleen weight and on spleen smears visible modifications of the distribution into categories of cells which are classified by the mean of their maturation degree, suggested that these both types of modifications are bound. Therefore, the classic cytological study seems to be a really good tool for analysing the effects of this kind of grafting on the haemopoietic organs, the weight modifications of which are difficult to measure. On the other hand, this method allowed us to see that the distribution of the cell population in the weakly enlarged spleens is very different from both distribution of the population in the strongly enlarged spleens and the controls ones ; this heterogeneity of the stimulating effect of the graft asked us the question whether this one could exerce its influence by the mean of two different ways, at least, or by only one.


[Active transport of calcium in thymocytes]. Calcium uptake was studied on thymocytes from rabbits with 45Ca loading followed by rapid filtration. Datta shown that the substrates of the mitochondrial electron transport chain did not allowed calcium uptake. Exogenous ATP was required to observe a large influx of calcium in thymocytes. Succinate, magnesium and phosphate ions increased this ATP induced influx of calcium, which was not completely inhibited with atractyloside or ruthenium red.


[Enzyme and protein release from human granulocytes: effect of ATP]. The authors study the proteins and enzymes release of resting and phagocytosing human leukocytes suspended in Krebs-Ringer-Phosphate milieu containing or not glucose. They measure the metabolic level and the percentage of enzymes release and show the influence of ATP on this phenomenon. These results are in favour of a direct action of ATP on the cellular membrane.


[Effect of isoniazid on structure of human metaphase chromosomes]. Isoniazid gives rise to chromomerization of human bone marrow metaphase chromosomes in vitro or in vivo. The discontinuous appearance of the chromatids seems to be related to their progressive spiralization during the mitotic division. The medicinal substance tested would have the property of revealing the distribution of heterogenous chromatine by showing down its condensation procedure.


[Seasonal variation of arylesterase activity and its consequence for enzymatic hydrolysis of phenylacetate]. Studies on red cell arylesterase activity were performed for two years by  potentiometric titration using phenylacetate as substrate. From April to October enzymes had higher arylesterase activity than the rest of the year. During that period an increase of arylesterase activity by L-phyenyl-alanine had not been shown.


[Active exchange of Na and K in perfused and procaine arrested rat heart]. Recovery of normal Na and K contents of perfused and procaine arrested rat ventricules occurs with a rate constant of 0.109 mn-1 (i.e. 60% of restoration is achieved in 7.5 mn) after a 45 mn arrest of active transport produced by perfusion with a K free Krebs-Henseleit solution. Active Na efflux is nearly equal to K influx. Peak Na Efflux is estimated to be 11.2 muEq.g-1dry.mn-1 or 19.7 pM.cm-2.s-1, i.e. more than 4 times leakage flux of the resting heart. Na efflux is not proportional to Na intracellular concentration but to the square of this concentration.


[Role of ventral surface of brain stem in control of arterial pressure and in hypotensive action of clonidine]. Superficial destructions of the brain stem have been performed in cats at the level of the chemosensitive areas "S". These destructions produced a drop in blood pressure, which was transient in 9 and definitive in 4 animals. In 6 sham-operated animals, clonidine (15 mug/kg), injected intravenously, always induced a marked fall in blood pressure, whereas in the 10 animals which have maintained or regained normal blood pressure after the destruction of the areas S, clonidine no longer induced any decrease in blood pressure. These results suggest that the integrity of the areas S is necessary for the development of the hypotensive action of clonidine. This hypotensive drug may act, at least at that level of the ventral surface of the brain stem, through an inhibition of a vasopressive structure.


[Effect of d-1 propranolol on urinary osmolarity after furosemide in anesthesized dog]. The effects of propranolol (l mg/kg/H infused in the renal artery) on the diuretic action of furosemide (20 mg/kg i.v.) have been studied in pentobarbital anesthetized dogs. We obtained the 3 following results : the urine remained isotonic to the plasma during the 6 hours following the furosemide injection ; the urinary output of sodium and water, measured during 6 hours after furosemide injection, was increased ; the renin hypersecretion was inhibited.


[Change in rabbit plasma lipoprotein lipase activity after cephalic irradiation]. Modifications of the post-heparin lipoprotein lipasic activity in the plasma are studied after cephalic irradiation in the rabbit. Results indicate a 2/3 decrease of the enzymatic activity which is reduced to zero in half of the animals 16 hours after a 800 R irradiation.


[Correlations between Ph 1 clone and leukocyte alkaline phosphatase on their associaton: chronic myeloid leukemia and pregnancy]. A biological [karyotype, leucocyte alkaline phosphatase (L.A.P.), haematimetry] and clinical study was performed on three women carriers of a chronic myaloid leukemia during their pregnancy (3 1/2 months, 6 1/2 months), or just after delivery. The results show : (1) a relation between the acuteness of the illness and a higher rate of L.A.P., probably secondary to pregnancy, and (2) a relation between the clinical evolution and the rate of Ph1 (+) cells.


[Conditional suppression of a reflex in Drosophila melanogaster: acquisition and extinction]. In Drosophila it was possible to carry out a negative instrumental conditioning of the tarsal reflex (extension of the proboscis in response to a sucrose stimulation of the forelegs) : the insects could be trained to inhibit this reaction through a repetitive association of its releasing with a consecutive nociceptive stimulation. An experimental extinction procedure allowed the reflex to be resoted.


[Effect of practolol on experimental hypertension in dogs]. In the dog, the intra-venous injection of practolol (1 to 3 mg/kg) reduces the hypertension provoked by vagotomy and sino-aortic nerves section, or by intra-venous administration of potassium cyanide. But practolol differs from propranolol ; he does not modify hypertension observed after electrical stimulation of central end of saphene, laryngeal superior, or vagus nerf.


Levodopa in Huntingtons chorea.

Levodopa in Huntingtons chorea. Sixteen patients with Huntington's chorea were treated for periods as long as 8 months with levodopa. The condition of none of the patients improved; in fact, there appeared to be an exacerbation of chorea and dementia in addition to undesirable behavioural changes. Therefore, future use of levodopa in these patients is not warranted. The postulated association of low homovanillic acid values in cerebrospinal fluid and favourable response to levodopa therapy was not borne out.


Plasma hormone profiles in populations at different risk for breast cancer. Evidence suggests that the reliability of urinary androgens or estrogens as prognostic discriminants for breast cancer may vary with different populations and may bear little relation to changes in plasma hormone levels. In this study the plasma estradiol level was significantly lower in Bantu, but did not in Caucasian, women with breast cancer, while the proportion of plasma androstenedione to dehydroepiandrosterone increased in Bantu patients. These changes in the plasma hormone profile in Bantu patients, a low-risk population for breast cancer, imply a change in ovarian and/or adrenal activity. Lack of similar hormone changes in Caucasian patients may be due to the initial differences in the hormone profile between the healthy Caucasian and Bantu women and to the different environmental factors that promote the breast disease in Western women.


Hemodynamic and pathological results from experimentally induced left ventricular hypertrophy in the rabbit. Many studies of ventricular structure and function of the hypertrophied cardiac muscle have been performed using a model of right ventricular hypertrophy because a reliable experimental model for the chronically hypertrophied left ventricle was not available. Adult rabbits underwent thoractomy with placement of an ameroid band on the proximal aorta. The ameroid band closed to a maximal extent at 9 days. Systolic gradients were measured at 3 weeks. 37 animals (group I) were sacrificed at an average of 7 weeks, and 5 (group II) at 18 weeks. Specific cardiac chambers were weighed. The average left ventricular weight expressed as a percentage of body weight of control animals was 0.13 +/- 0.01 compared to group I 0.17 +/- 0.04 (P = 0.001) and group II 0.23 +/- 0.04. Hemodynamic data revealed significant aortic outflow obstruction with systolic gradients averaging at least 50 mm Hg. Left ventricular end-diastolic pressures were elevated in 13 of 29 animals compatible with left ventricular failure. These results indicate that this technique affords a reliable experimental model for inducing biventricular hypertrophy which can be evaluated hemodynamically.


The saccus dorsalis of the rainbow trout, Salmo gairdneri Richardson: histological, cytochemical, electron microscopical and autoradiographical observations. The saccus dorsalis of the brain of the rainbow trout, Salmo gairdneri Richardson, has been investigated by means of histological, cytochemical, enzyme-cytochemical, electron microscopical autoradiographical techniques. The saccus dorsalis is a rostro-dorsal evagination of the diencephalic roof, and consists of a partly folded epithelial wall separating the cerebrospinal fluid from the meningeal matrix fluid. The well-developed vascular system around the epithelial wall, consisting of capillaries with different diameters, seems to be part of the pineal vascular system. No structures were found that may be involved in a possible mechanical or nervous blood flow control. The single-layered epithelium consists of highly specialized cells of one specific type. These cells are mainly characterized by infolded basal membranes, long microvilli of a peculiar shape, non-folded lateral membranes bordering intercellular spaces, apical concentrations of elongate and cup-shaped macromitochondria, a basally located rough endoplasmic reticulum, an apically situated smooth endoplasmic reticulum and apical concentrations of micropinocytotic vesicles. Morphological evidence is presented of a multiple function of these cells: (1) fluid secretion, (2) extrusion of low molecular weight organic substances into the ventricular system, (3) uptake of high molecular weight substances, and (4) uptake of low molecular weight organic substances (aminergic neurotransmitters [GABA]) from the cerebrospinal fluid. The significance of light and dark cells is discussed. Indications of a possible innervation of the saccus dorsalis epithelial cells were not observed. The functional significance of the saccus dorsalis (possible analogue of the choroid plexus?) is discussed.


Ultrastructural alterations in skeletal muscle fibers of streptozotocin-diabetic rats. The ultrastructure of fast-twitch-oxidative-glycolytic (FOG), fast-twitch-glycolytic (FG) and slow-twitch-oxidative (SO) fibers in plantaris and soleus muscles of normal and streptozotocin-diabetic rats was studied. In the diabetic animals, the mitochondria of FOG and SO fibers showed a loss of cristae and an increase in electron-dense granules. There was also an increased number of lipid droplets in close proximity to the mitochondria and the nuclei, and a separation of individual muscle nuclei to form satellite cells. Higher incidences of surface projections and sarcoplasmic splittings at the nuclear region were noticed in SO fibers. The FG fibers showed some disorientation of the T-tubular system. It is concluded that streptozotocin-diabetes has differential effects on the fine structure of the three fiber types of rat skeletal muscle.


Pumping ability of the hypertrophying left ventricle of the spontaneously hypertensive rat. Cardiac pumping ability was assessed during the natural development of left ventricular hypertrophy by elevating venous pressure by infusing Tyrode's solution intravenously to produce peak cardiac output. This experiment was performed on spontaneously hypertensive rats (SHR) of three age groups (11, 24, and 83 weeks). From 11 to 24 weeks, peak cardiac output of SHR increased in direct proportion to the abnormally increased ventricular mass; Thus peak cardiac output per gram of left ventricle (LV) remained stable. Similar results were obtained for two strains of normotensive rats at each of the same three age groups. Thus, in the normotensive animal peak cardiac output per gram of LV remained stable over a wide range of ages and varying left ventricular weights. However, with progressive elevation of arterial pressure in aging SHR (83 weeks), we observed severe ventricular hypertrophy (100% increases in left ventricular to body weight ratio). In this oldest SHR group, unlike age-matched normotensive rats, there was a marked reduction in the pumping ability per gram of LV. Thus, during the natural development of left ventricular hypertrophy SHR demonstrated both a stable stage of hypertrophy in which the increased left ventricular mass maintained its pumping ability, and a later stage of deterioration in which there was a loss of the normal relationship between ventricular mass and pumping ability.


Effects of mechanical activity and hormones on myocardial glucose and fatty acid utilization. The effects of increased cardiac work on glycolysis, the citric acid cycle, and oxidation of fatty acids were studied in isolated rat hearts. Glycolysis was stimulated by increased work in heart perfused with glucose alone or with glucose, high levels of insulin, and low levels of palmitate. With glucose alone, stimulation was associated with a rapid decrease in phosphate potential and rapid activation of phosphofructokinase, but an apparently slower activation of glucose transport. With glucose, insulin, and palmitate present, stimulation of glucose utilization was rapid and correlated with activation of phosphofructokinase.


Depressed function of a ouabain-sensitive sodium-potassium pump in blood vessels from renal hypertensive dogs. Vasodilator responses to acute intra-arterial infusions of K+ are attenuated in dogs with chronic one-kidney perinephritic hypertension in rats with chronic two-kidney Goldblatt hypertension, and in men with essential hypertension. There is evidence that K+ evokes vasodilation by stimulating vascular smooth muscle membrane Na+-K+-activated adenosine triphosphatase, thereby increasing activity of the cellular Na+-K+ electrogenic pump. We therefore proposed that there may be an underlying decrease in the operation of this pump in vascular smooth muscle of hypertensives. The operation of the cellular Na+-K+ pump may be estimated by measurement of rubidium uptake. Thus, so further investigate our hypothesis, we measured 86Rb uptake in small mesenteric arteries and splanchnic veins from 12 dogs with chronic uncomplicated one-kidney perinephritic hypertension and from 12 normotensive control dogs. Vessels were excised under thiamylal anesthesia and incubated in cold medium (plasma or Krebs-Henseleit solution) for sodium loading and then the velocity of 86Rb uptake was estimated in the absence of or in the presence of ouabain, a specific inhibitor of the Na+-K+ pump. In neither arteries nor veins was there evidence for differences between hypertensives and normotensives in the ouabain-insensitive uptake of 86Rb. In contrast, the ouabain-sensitive 86Rb uptake was depressed by 42% in arteries (P less than 0.05) and by 49% in veins (P less than 0.01) from hypertensive dogs, if incubated in the dog's own plasma. These results indicate that the activity of a ouabain-sensitive Na+-K+ pump may be depressed in vascular tissue from dogs with chronic one-kidney perinephritic hypertension. Because the Na+-K+ pump in vascular smooth muscle is probably electrogenic, such an abnormality, by partially depolarizing the muscle cell membrane, would help to account for the elevated vascular resistance found in these dogs.


The frontal chest film as a method of suspecting transposition complexes. The frontal chest film as a means of suspecting transposition complexes is discussed. The first step is recognizing the normal relationships formed by the ascending aorta, an aortic knob-descending aorta, and pulmonary trunk. The concept of which ventricle is connected to which atrium is developed--the terms ventricular noninversion and inversion being utilized. Frontal chest film signs of transposition are summarized as follows: 1) in the majority of transposition complexes, absence of the pulmonary trunk is the premier sign; 2) patients with ventricular noninversion tend to show the ascending aorta and aortic knob-descending aorta in normal position. Patients with ventricular inversion usually show absence of all three great artery relationships. 3) In ventricular inversion, the left heart border shows a septal notch or a diffuse convex bulge (two ventricles), or a discrete bulge high up on the left border (single ventricle).


Echocardiography in Wolff-Parkinson-White syndrome. Twenty-six patients with Wolff-Parkinson-White (WPW) syndrome were studied by echocardiography. They were classified into the following WPW types: anterior right ventricular pre-excitation (Type I) - six patients; posterior right ventricular pre-excitation (Type II) - six patients; posterior left ventricular pre-excitation (Type III) - fourteen patients. Twenty-three patients were in WPW at the time of study. Four patients with Type I WPW had abnormal systolic motion of the interventricular septum: three paradoxical and one flat. Patients with Type II and Type III WPW had no septal motion abnormalities related to pre-excitation. Three patients had intermittent WPW, Type III; in all three only minor changes in normal septal motion were apparent on WPW beats. Associated cardiac abnormalities were evident in six patients: two mitral prolapse (one Type II WPS and one Tpe III); one idiopathic hypertrophic subaortic stenosis (Type III); one congestive cardiomyopathy (Type III); one hypertrophic nonobstructive cardiomyopathy (Type I); and one atrial septal defect (Type II). We conclude that abnormal interventricular septal motion may occur with Type I WPW abnormality. Other abnormalities are detectable by echocardiography in a high proportion of WPW patients, but do not appear to be associated with any single Wolff-Parkinson-White type.


Echocardiographic studies of abnormalities associated with coarctation of the aorta. Echocardiograms were performed in thirty-six patients (aged 4 to 36 years) with proven coarctation of the aorta. Nineteen patients (53%) were found to have marked diastolic eccentricities of their aortic valves (Eccentricity Index greater 1.5), indicating the presence of bicuspid aortic valves. One of these patients also had multilayered aortic root echoes in diastole. Five patients had angiographic proof of their aortic valve morphologies which corroborated the echo findings. Five patients with bicuspid aortic valves showed mitral valve diastolic flutter indicative of aortic regurgitation. Idiopathic hypertrophic subaortic stenosis (IHSS) was suspected in four patients (11%) with abnormal systolic anterior motion of the mitral valve; three of these patients also had asymmetric septal hypertrophy. There was catheterization proof of IHSS in one patient. Two patients (5.6%) demonstrated mitral valve proplapse.


Increased somatostatin content of islets from streptozotocin-diabetic rats. Pancreatic islets were isolated from control and streptozotocin-diabetic rats. Somatostatin content as determined by radioimmunoassay was strikingly increased in the diabetic group. Immunoreactive insulin content was markedly reduced and glucagon was moderately increased. The mechanisms responsible for the somatostatin changes are unknown.


An anomaly in the inheritance of haptoglobin types in Down's syndrome: a study of mother-child pairs. A sample of 95 mother-child pairs provided evidence that plasma haptoglobin (Hp) types are inherited in an unusual manner by children with Down's syndrome. Homozygous mothers gave birth to more homozygotes and fewer heterozygotes than expected. Among offspring of heterozygous mothers, the frequencies were distributed essentially as expected. No abnormality was found in a normal control sample of 151 mother-child pairs. Using this material it was demonstrated that the anomalous Hp inheritance in Down's syndrome was not due simply to an increase in maternal age when the children were born.


Clinical diagnosis of Down's syndrome.

Clinical diagnosis of Down's syndrome. A physical examination checklist of 25 signs of Down's syndrome was used to predict the presence of absence of 21-trisomy in 291 individuals examined for suspected Downs syndrome. Using only total numbers of signs present, 21-trisomy was unambiguously predicted in about half those examined. Discriminant analysis using the most informative 10 signs misclassified only 11 of 169 infants aged 2 years or less, and allowed non-overlapping classification into Down's and non-Down's of almost three-fourths of suspected individuals. The risk for Down's syndrome in the overlap area was 58%.


Immunological capacity of lymphocytes from untreated patients with Hodgkin's disease evaluated in mixed lymphocyte culture. Blood lymphocytes from thirty-nine untreated patients with Hodgkin's disease were tested for stimulatory and responding capacity in mixed lymphocyte culture. The response to allogeneic lymphocytes was impaired in ten patients but the mean response of the patient group did not differ from healthy controls. Lymphocytes from female patients responded better than male patients (P less than 0-02). The stimulatory efficacy was severely impaired in patients' lymphocytes (P less than 0-001). Age, clinical stage and histopathology had no significant influence on the responding or stimulatory capacity.


Depressive effect of serum from patients with leprosy on mixed lymphocyte reactions. Influence of anti-leprosy treatment. Mixed leucocyte cultures, from two normal donors, were set up in media containing human serum from one of the following sources: (a) a pool of normal group AB donors; (b) Chinese, Malay or Indian patients with untreated leprosy; (c) the same patients after effective anti-leprosy treatment; (d) control Chinese, Malay or Indian subjects. Transformation was estimated by measuring the incorporation of tritiated thymidine in the last 24 hr of a 7-day culture period. Transformation was impaired in sera from treated lepromatous patients, but was less impaired  or not impaired at all in sera from treated lepromatous patients. The loss of depressive activity after treatment was more marked in Chinese and Indian than in Malay patients. Transformation was also impaired, though to a lesser extent, in sera from patients with untreated tuberculoid leprosy; it was still impaired in sera from treated tuberculoid patients. There was no evidence of specificity in impairment of mixed lymphocyte reactivity and lymphocytotoxic antibodies appeared to play no role. The incidences of hepatitis B antigen and antibody and of anti-nuclear factor were not notably high.


Mixed leucocyte culture blocking factor activity in allograft recipients and its role in the clinical outcome of human cadaveric renal allografts. Seventeen renal allograft recipients were followed serially both pre- and post-transplantation for the presence of mixed leucocyte culture blocking factor activity (MLC-BFA) in their plasma. Patients could be divided into three distinct groups on the basis of MLC-BFA and lymphocytotoxin (LT) determinations. Fifteen out of seventeen patients possessed MLC-BFA at one time or another while four out of seventeen were positive for LT. Four patients of group 1 with pre-transplant LT and MLC-BFA rejected their grafts within 1 year. Two LT negative patients of group 2 developed no detectable MLC-BFA during a follow-up period of over 1 year. One other patient developed MLC-BFA 8 months following transplantation. All three patients had an excellent clinical course. Ten patients belonging to group 3 possessed no LT or MLC-BFA prior to transplantation but developed MLC-BFA alone after receiving an allograft. Only one patient rejected his allograft within 2 months. The remaining nine patients experienced mild rejection crises during the first 3 months after transplantation but had excellent renal function at 1 year or beyond that time. Our results indicate that MLC-BFA in the presence of LT may not prevent rejection. MLC-BFA is associated with a good clinical course in LT negative patients. However, certain patients who fail to develop LT or MLC-BFA in spite of repeated blood transfusions prior to transplantation may also do extremely well in the absence of detectible MLC-BFA.


Mechanism of trapping of immune complexes in joint collagenous tissues. The role of acute inflammation and of pre-existing specific antibody in the retention of intra-articular antigen in joint collagenous tissues of immunized rabbits was examined. The role of the acute synovitis occurring immediately after antigen injection was investigated by the production of acute synovitis in immune and non-immune rabbits. In no case was more 125I-labelled BSA retained in the inflamed joint tissues compared to the contralateral non-inflamed joints 7 days after intrarticular antigen injection. When antigen retention was examined early after intra-articular injection, the largest amount of antigen was retained 30 min after injection, before the appearance of the acute inflammatory synovitis. These findings suggest that acute inflammation does not constitute a major factor in the long-term retention of antigen in collagenous tissues. To investigate the role of antibody in the retention of antigen, non-immune rabbits were injected intravenously with purified anti-BSA antibody 3 days prior to the intra-articular injection of BSA. Over 20 times more antigen was retained irreversibly in collagenous tissues obtained from the injected joints of passively immunized animals compared with similar tissues of control rabbits. When rabbits were injected intravenously with purified anti-BSA antibody and either killed 20 mins or 3 days later, in vitro binding of antigen by joint collagenous tissues was seen only in animals where antibody was allowed to equilibrate with the extravascular space for 3 days. These findings indicate that retention of antigen depends on the presence of extravascular antibody. Antigen retention in collagenous tissues was also present when both antibody and antigen were injected intravenously and antibody was given 3 days before the antigen. It is concluded that the trapping of immune complexes in collagenous joint tissues of immunized animals depends on: the presence of antibody in the extra-vascular space; the diffusion of antigen or soluble complexes into this space; the interaction of antigen or soluble complexes with extravascular antibody with subsequent formation of larger and more insoluble complexes; and the trapping of these complexes within the collagen fibre meshwork.


Effect of induced elevated plasma levels of homocystine and methionine in rats on collagen and elastin structures. Young growing rats were intraperitoneally injected with mixtures of homocystine and methionine for several weeks. The growth of the animals was inhibited. After 3 weeks 25% of the rats died and isolation of tail tendon collagen and aorta elastin showed that these proteins were deficient in chemical cross-links. Seventy-five % of the rats survived further injections for another 3 weeks and isolated collagen and elastin were found to be normal in cross-linking. The variability in susceptibility of these rats to homocystine-methionine treatment is discussed in relationship to human homocystinuria. It is speculated that the variability is due to variability in in vivo homocysteine levels.


The cyanogen bromide peptides of bovine soluble and insoluble collagens. I. Characterization of peptides from soluble type I collagen by sodium dodecylsulphate polyacrylamide gel electrophoresis. Acid soluble collagen and purified alpha1 and alpha2 chains were prepared from bovine skin and digested with cyanogen bromide. The resultant peptides were separated by electrophoresis on polyacrylamide gels containing sodium dodecylsulphate. Thirteen peptides obtained from the alpha1 chain and two from the alpha2 chain were identified as overlapping sequences containing methionine-derived peptide bonds not cleaved during the reaction. Those uncleaved peptides from the alpha1 chain accounted for approximately 30% of the total digest, as determined by planimetry on the staining profiles, and their relative proportions indicated that efficiency of cleavage at specific methionine residues was dependent upon position in the sequence. Alpha1CB5-8 was most resistant to cleavage while alpha1CB0,1-2 and alpha1CB7-6 were most susceptible. Peptides of a 2:1 (w/w) mixture of alpha1 and alpha2 chains and of the acid-soluble collagen gave electrophoretograms which were essentially a summation of those obtained from the individual chains.


The cyanogen bromide peptides of bovine soluble and insoluble collagens. II. Tissue specific cross-linked peptides of insoluble skin and dentin collagen. Cyanogen bromide peptides were prepared from insoluble bovine skin and dentin collagens and compared by electrophoresis in polyacrylamide gels containing sodium dodecylsulphate, with those of the alpha1 and alpha2 chains of soluble type I and type III collagen. Both insoluble collagens yielded predominantly the peptides of type I collagen. Insoluble skin collagen was approximately 13% type III. Type III collagen if present in dentin, is present in smaller quanitity not detected by the technique used here. Several new fragments, different in each tissue, were obtained which could not be accounted for as uncleaved peptides. Three of those from dentin were isolated by gel chromatography and characterized by amino acid analysis. Two were found to contain 3-hydroxyproline, suggesting the presence of alpha1CB6. The recovery of only 25-30% of alpha1CB6 in the expected position on SDS gel electrophoresis indicated that it was involved in interactions with other peptides in these two tissues to the extent of one and a half cross-links per tropocollagen molecule. The nature and distributin of cross-link peptides of bovine skin and dentin collagens was distinctly different.


Polydisperse distribution of acidic glycosaminoglycans in bovine kidney tissue. Distribution of acidic glycosaminoglycans in bovine kidneys was investigated after fractionation by ion exchange chromatography and gel filtration. The fractionated acidic glycosaminoglycans were characterized by electrophoresis on cellulose acetate membranes before and after specific enzyme digestion. Chondroitinases were used to detect the chondroitin sulfate isomers by demonstration of the disaccharide subunits and to distinguish the other acidic glycosaminoglycans by their resistance to the enzymes. The polydispersity of heparan sulfates, which accounted for two fifths of the total kidney glycosaminoglycans, was demonstrated with respect to the degree of sulfation and molecular weight difference. Hyaluronic acid accounted for approximately one fourth of the total glycosaminoglycans and was distributed in fractions of relatively higher molecular weight. Chondroitin sulfate isomers contained in decreasing amounts the disaccharide components of dermatan sulfate and chondroitin 4- and 6-sulfates.


Characterization of lipids associated with macromolecules of the intercellular matrix of human aorta. Macroscopically lesion-free parts of human aortas with no or light lesions (group I) and advanced atherosclerotic lesions (group II) were submitted to a series of successive extractions in order to "solubilize" all the macromolecular components of the arterial wall ("chemical dissection"). Lipids were extracted with methanol-chloroform from all these macromolecular fractions and analyzed for cholesterol, triglycerides, phospholipids. The fatty acid composition of the separated fractions was determined by GLC. The lipid composition and fatty acid spectrum of the macromolecular fractions of group I and group II aortas was compared. Total lipids increased in the freely extractable ("non associated lipids, approximately 78% of total) fraction as well as in the fraction "associated" with collagen and elastin. Free and esterified cholesterol increased also both in the "freely extractable" and in the collagen-elastin-associated lipids", approximately 78% of total) fraction as well was higher (+ 100%) than that of free cholesterol (+ 60%). Triglycerides increase also by 15 to 70% in all fractions except in the elastin-associated fraction. Free fatty acids increased by 40 to 400% in all extracts associated with macromolecular fractions but not in the "freely extractable" fraction where they decreased. Phospholipids show less marked variations (approximately less than 10%) and decrease in the elastin associated lipids of group II aortas. The fatty acid spectrum of group II lipids associated with macromolecules differs from that of group I. There is a relative increase of longer chains (C greater than 18, especially 20:1 and 20:2 acids). No such increase in the "long" fatty acids was seen in the "freely extractable" lipid fraction. Elastin isolated from group II aortas is significantly enriched in total lipids, cholesterol (free and esterified) and free fatty acids and contains the widest spectrum of fatty acids (from 11:2 to 22:1) with a significant fraction of total fatty acids as "odd" carbon chains. There appears to be a correlation between the decrease of triglyceride-bound fatty acids and the increase of free fatty acids. The free fatty acid concentration exceeds both in group I and II aortas the concentration of fatty acid esters. This increase in free fatty acids "associated" with intercellular matrix macromolecules and especially with elastin may be the result of an increased hydrolysis of esters and/or a decreased esterification in advanced atherosclerotic aortas. The accumulation of long chain and "odd" fatty acids in elastin may be an important factor in its accelerated degradation during the atherosclerotic process.


An autoradiographic assessment of the incorporation of H3-uridine into DNA and RNA of osteoblasts of aging mice. Intracellular labeling of DNA and RNA after H3-uridine administration was investigated autoradiographically during aging. Five to 78 weeks old mice were injected with 5 muCi of H3-uridine/gm of body weight and were killed from 15 minutes to 30 days later. Five mum decalcified sagittal sections of femora were treated with RNAase, DNAase or appropriate buffers. Autoradiographs were prepared and grain counts were made over diaphyseal periosteal osteoblasts. Both DNA and RNA incorporated H3-uridine. RNA label was 88 to 95% of the total cell label. DNA labeling ranged from 2 to 5%. DNA labeling appeared slightly increased after longer exposure to H3-uridine, whereas, RNA labeling remained relatively unaltered. With increasing age, incorporation into DNA decreased, whereas, RNA label showed a slight increase. A variable amount of non-specific label was undigested by either enzyme and may reflect insoluble conversion and/or degradation products. Apparently, some conversion of uridine into a DNA precursor occurs without loss of tritium label, thus rendering uridine less than totally specific for RNA. Nevertheless, the uptake of H3-uridine is largely indicative of RNA biosynthesis especially in skeletal cells that are not normally highly proliferative.


The effect of a strongly-interacting macromolecular probe on the swelling and exclusion properties of loose connective tissue. Poly(L-lysine), a cationic polypeptide known to undergo specific interactions with acid mucopolysaccharides, is used as a macromolecular probe in an investigation into the structure of loose connective tissue. The polypeptide apparently binds, via an electrostatic mechanism, to the mucopolysaccharide component of the tissue, leading to a reduction in the swelling of the tissue. The polypeptide does not, however, have a deswelling effect on the tissue; the ultimate reduction in swelling is influenced by the absolute amount of polybase which enters the tissue during the swelling process. Dextran 2000 is found to have a dwelling effect on the tissue which is independent of the action of the polypeptide; this is suggestive of a large degree of independence between the collagen network and the mucopolysaccharide-containing matrix. The polypeptide, moreover, causes a reduction in the excluded volume of the tissue.


[Laparoscopy in patients with Hodgkin's disease (author's disease)]. Laparoscopy with spleen and multiple liver biopsies was performed in 94 patients with Hodgkin's disease in stages III B and IV B. In four of them involvement of the liver was demonstrated in this way. Exploratory laparotomy was subsequently performed in 35 patients, liver involvement being revealed in only one patient in whom it had not been previously demonstrated by laparoscopy and (or) biopsy. While laparoscopy proved to be of similar value to exploratory laparotomy in assessing liver involvement, it was no substitute for operation. It was valuable in determining the stage of the disease and following its course.


[Effect of leukemic sera on the reactivity of leukocytes from acute leukemia patients in mixed lymphocyte cultures]. The author examined the action of leucemic sera (first attack, repapse and remission) on the reactivity of lymphocytes, obtained from patients with acute myeloblastic (AML) in mixed cultures of lymphocytes, which was compared with the reactivity in the medium of fetal calf serum and pool of normal human serum. Twelve out of 21 Leucemic sera, obtained from patients with AML during their first attack or relapse inhibited completely the mixed lympholytec cultures under autologic conditions. Eight leucemic sera with established inhibiting action under autologic conditions preserved it under allogenic conditions as well. Sera of patients with acute myeloblastic leucosis during remission did not have inhibiting action on mixed lymphocytic cultures. These results suggested the presence of factor(s) in the sera of patients with acute myeloblastic leucosis during the first attack or relapse, which inhibited mixed lymphocytic cultures.


[Streptozotocin diabetes in the rat with special reference to glucose utilization by the musculature]. The glucose utilization by different skeletal muscle tissues of short-term streptozotocin treated Wistar rats was studied both in vivo and in vitro. The findings permit the following statements: The reduced metabolic conversion of glucose is mainly the result of the diminished transport of glucose into the muscle cells. The utilization of the glucose taken up by the muscle cells for synthesis of glycogen is unchanged in the diabetic animals and can be stimulated by insulin correspondingly as in normal rats. The conversion of the glucose metabolized by the cells to lactate and the time course of the specific activity of glycogen and lactate lead to the conclusion that glycogenolysis in the muscles of streptozotocin diabetic rats during the incubation is enhanced.


[Placental changes in rats with streptozotocin diabetes]. Placentas of rats with diabetes mellitus induced by streptozotocin are investigated. Histologically, in the spongiosa zone we find dilated and congested maternal sinus as well as cysts of different size and number. These cysts contain granular eosinophilic material and cytotrophoblastic cells with large amount of glycogen. In our opinion, these cysts are large glycogen islets of the spongiosa zone respectively their remnants. However, similar findings we see in smaller extension in normal rat placentas too. The glycogen content in placentas of diabetic rats is in all localisations higher than in control cases. Comparable histological changes like in diabetic human placenta such as placental disturbances of maturation we don't find in the placental labyrinth of diabetic rats.


Meclofenamate does not reduce chronic hypoxic pulmonary vasoconstriction. There was no reduction in the pulmonary pressor response to hypoxia following inhibition of prostaglandin synthesis in rats exposed to chronic hypoxia. A fall in left ventricular weight suggested that systemic pressure may have been reduced after inhibition of prostaglandin synthesis in normoxic rats.


Effect of X-537A- on the phosphorylated protein in sarcoplasmic reticulum vesicles. The effect of the antibiotic X537A on the phosphorylated ATPase (E approximately P) was investigated. The results show that X-537A depresses the level of E approximately P which is dependent on the Ca2+ gradient, while the Ca2+-independent E approximately P is not affected.


Effect of heat treatment on the ATPase activity of various sarcoplasmic reticulum preparations. Ca2+-stimulated ATPase activity of sarcoplasmic reticulum (SR) preparations is activated after a short period of preincubation at temperatures between 40 and 45 degrees C, but for temperatures higher than 48 degrees C pronounced denaturation is observed. Heat denaturation is decreased if Mg2+ or K+ are present during heat treatment.


Fibrillation of tropoelastin induced by proteoglycan. Electrostatic interaction between tropoelastin, the native precursor of elastin, and proteoglycan results in tropoelastin fibrillation. The finding suggests a possible involvement of proteoglycans in elastogenesis.


A synthesis of interstitial fluid regulation and lymph formation. The interstitial fluid spaces are filled with a mat of collagen fibers, and the interstices of this mat contain a mucopolysaccharide gel ground substance. Both the collagen fibers and the gel are elastic structures that can be expanded or compacted. In the expanded state the collagen fibers are pushed far apart and pockets of free fluid develop witin the gel. In the compacted state the elastic recoil of the compressed collagen fibers and gel reticular fibrillae seems to cause suction on the fluid within the tissue spaces, thus creating a subatmospheric pressure. Measurements of interstitial fluid pressure using a perforated capsule method indicate that this is normally slightly negative (subatmospheric) in most soft tissues. However, even very slight extra filtration of fluid into the tissue spaces increases the interstitial fluid pressure toward more positive values, which in turn increases lymph flow. The increased lymph flow then decreases the interstitial fluid volume and pressure back toward normal because of two mechanism, 1) direct removal of fluid from the tissue spaces in the lymph, and 2) removal of protein from the interstitial fluid in the lymph, thus decreasing the interstitial fluid colloid osmotic pressure and allowing more effective osmosis of fluid directly from the interstitial spaces back into the capillaries.


Glucagon secretion from the perfused pancreas of streptozotocin-treated rats. One hour following intravenous streptozotocin, rat pancreases were perfused in situ, and , in contrast to saline-injected controls a marked decrease of insulin secretion was observed. In these streptozotocin-treated animals, baseline glucagon secretion was enhanced when the perfusate glucose concentration was either 80 mg./100 ml. or 300 mg./100 ml. In addition there was hypersecretion of glucagon in response to arginine. Exogenous insulin (20,000 muU./ml.) could suppress glucagon secretion when endogenous secretion was plentiful. Baseline and arginine-stimulated glucagon secretion of the streptozotocin treated animals was not suppressed by large amounts of glucose and insulin to the degree seen in control animals. The glucagon rise in response to an abrupt fall of glucose from 80 mg./100 ml. to 25 mg./100 ml. was not significantly higher in the control group than in the streptozotocin group. The results seen with epinephrine were in sharp contrast to those found with arginine. Epinephrine-stimulated glucagon secretion was not enhanced in the streptozotocin group. In addition, epinephrine-induced secretion could be suppressed by exogenous insulin in both the control and streptozotocin groups. The differences may be secondary to differences of endogenous insulin secretion. The present results are compatible with the hypothesis that local insulin secretion can exert a significant suppressive effect upon the alpha cell and that the inhibition of glucagon secretion by glucose is partially mediated by this mechanism. Furthermore, anomalous local insulin secretion may contribute to the abnormal glucagon secretion of diabetes mellitus.


Autoradiographic study of the distribution and cellular uptake of (14C) - streptozotocin in the rat. The distribution and cellular accumulation, in the rat, of three specifically 14C-labelled forms of streptozotocin were investigated. A significant pancreatic accumulation of radioactivity was observed with (3' -methyl-14C)-streptozotocin only. Autoradiographic studies revealed high levels of bound radioactivity in the islet tissue following the administration of (3 -methyl-14C)-streptozotocin whereas much lower levels of radioactivity were detected in the pancreatic tissue following the administration of either (1-14C)-streptozotocin or (2' -14C)-streptozotocin. In the pancreasea, the amount of radioactivity bound to islet tissue was always significantly higher than that bound to acinar tissue. In addition to the islet tissues, the kidney cortex showed a very high level of bound radioactivity after the administration of (3' -methyl-14C)-streptozotocin. The results suggest that streptozotocin is rapidly metabolised by the rat. The apparent specificity for the accumulation of radiolabel from (3' -methyl-14 C)-streptozotocin suggests that a metabolite derived from the methyl bearing ureido side chain of the drug may be specifically involved in the induction of tissue damage and the consequent development of diabetes.


Human adipose tissue in culture V. Studies on the metabolic effects of insulin. Specimens of human adipose tissue were cultured for one week with or without the addition of insulin. The basal as well as the noradenaline-stimulated lipolysis were enhanced in the explants cultured with insulin, showing that the long-term effect of the hormone is lipolytic. However, an acute antilipolytic effect of insulin could be demonstrated in these explants in the subsequent short-term incubations. The basal rate of glucose incorporation into the lipids was enhanced in the explants cultured with insulin. When insulin was added in the short-term incubations these explants did not further respond to the hormone while this was the case with the explants cultured without insulin. Thus, it seems that prolonged exposure to insulin leads to a diminished acute effect of the hormone on glucose metabolism. However, the same explants responded to the antilipolytic effect showing that insulin was able to bind itself to the membrane. The activities of hexokinase (HK), glucose-6-phosphage dehydrogenase (G6PDH), pyruvate kinase (PK) and lactate dehydrogenase (LDH) were increased in large fat cells both in freshly excised tissue and in cultured explants. However, the activity of phosphofructokinase (PFK) did not correlate with the cell size. The presence of insulin during the culture period enhanced the activities of G7PDH, PK, and LDH, while this was not found for HK or PFK. The data thus suggest that the metabolic capacity of human fat cells is enhanced by long-term exposure to insulin. Although enzyme induction could be shown for G6PDH, PK and LDH it seems unlikely that this is of importance for the increased rates of glucose metabolism in these explants since the rate-limiting enzymes, HK and PGK, were not increased. Most probably, then, this stimulating effect of insulin is exerted on the membrane and the rate of glucose transport.


Effects of long-term restricted insulin production in obese-hyperglycemic (genotype ob/ob) mice. Primary hypersecretion of insulin has been suggested as one possibility for the genetic fault of ob/ob mice. To test this hypothesis, streptozotocin (SZO) was used to reduce permanently insulin secretion in young lean and obese mice. After establishment of hyperglycaemia and weight reduction in treated obese mice (obese-SZO), daily insulin replacment was begun in some (obese-SZO-Ins). Obese-SZO mice maintained insulin levels and body weights similar to lean controls, though they were shorter and fatter, while food intake and blood sugar levels exceeded lean values. Obese-SZO-Ins mice with reduced islet hyperplasia, but great insulin resistance, gained more weight than obese-SZO mice; had high serum insulin and controlled blood glucose; and exhibited hyperphagia. These results suggest that primary hypersecretion of insulin cannot be the genetic defect, as ob/ob mice are hyperphagic, hyperglycaemic, insulin resistant, and "obese" even when insulin levels are restricted.


Mouse strain difference in the expression of antitumor activity of PS-K. Effect of PS-K on tumor growth and antibody production was studied in inbred C57BL/6, SL, C3H/He, and AKR mice, and in colony-bred ICR mice. (1) PS-K exhibited antitumor activity on sarcoma-180 in ICR mice, but not in AKR mice. Growth of sarcoma-180 was suppressed to the intermediate extent in other strains. (2) In ICR strain, antibody production against trinitrophenyl was depressed in mice bearing sarcoma-180 and restored by PS-K. In AKR mice, on the other hand, antibody production was not depressed in tumor-bearing state and was not augmented by PS-K. Other strains showed intermediate degrees of suppression of antibody-producing capacity by sarcoma-180 and its restoration by PS-K.CR strain, the growth of Ehrlich tumor as the challenge tumor was enhanced in mice bearing sarcoma-180 as compared to that in controls. After the treatment with PS-K in this strain, however, not only the growth of sarcoma-180 but also of Ehrlich tumor was inhibited completely. On the other hand, the growth of Ehrlich tumor in AKR strain was neither enhanced in mice bearing sarcoma-180 nor inhibited by PS-K.


Antitumor effect of protein-bound polysaccharide preparation, PS-K, against 3-methylcholanthrene-induced fibrosarcoma in C57BL/6 mice. The protein-bound polysaccharide preparation, PS-K, was found to possess an antitumor effect against 3-methylcholanthrene-induced fibrosarcoma in mice which was shown to have a tumor-specific transplantation antigen. This antitumor effect seemed to be exerted through a host-mediated tumor immunity.


Intrahepatic cholestasis after griseofulvin administration. The occurrence of cholestatic jaundice in a patient receiving griseofulvin is described. The clinical manifestations, laboratory features, and pathological lesion of drug-induced hepatotoxicity are discussed. Complete recovery followed the discontinuation of drug administration. The potential hepatotoxicity of griseofulvin and the importance of close monitoring of liver function studies in patients receiving this drug are emphasized.


[Surgical procedures for sterilization of the women: certainty--complications (author's transl)]. The time (interval, postpartum, postabortum), location (uterus, mucus membrane of the oviducts, tubes), access (transcervical, transvaginal, trans-abdominal) and the actual method of sterilization for the women (surgical, electric, thermic, mechanical) can be differentiated and combined with each other in various ways. Today the usual procedure is sterilization by partial resection of the oviducts performed laparoscopically in the interval via electrocoagulation and surgically after delivery via periumbilical minilaparotomy. Laparoscopic sterilization via electrocoagulation has a rate of failure of about 1:1,000 and the mortality rate is less than 1:10,000. The most frequent complications are: hemorrhages due to injury of the larger vessels and burns in the intestine caused by the electric current. For this reason, conventional (:unipolar") electrocoagulation should be replaced by the so-called bipolar coagulation or other newer methods which avoid these complications. On the basis of the current literature, no definitive statements can be made regarding the reliability of the newer methods (silastic ring, plastic clips, thermocoagulation). An additional, although up until now purely hypothetic, advantage of the newer methods is the possibility of reversibility. With conventional electrocoagulation, the rate of reversilbility is very low. Additional alternatives are also culdotomy and minilaparotomy in the interval with the assistance of a uterus elevator. Both ways of access may be combined with various methods of sterilization. The pros and cons of the hysterectomy as a method of sterilization are still being discussed. Occasional late sequelae of sterilization such as menstrual disorders, pain and, particularly, problems related to sexual intercourse have only recently come to light. They have not yet been adequately investigated.


Phenotypic diversity among alleles at the per-1 locus of Neurospora crassa. Comparison of 11 perithecial color mutants suggested that all were alleles at the per-1 locus but nonetheless separable into two groups because of phenotypic differences. Three of the mutant strains produced orange perithecia and black ascospores, and eight produced paler, yellow perithecia and white ascospores. Perithecial phenotype was dependent upon the genotype of the protoperithecial parent; ascospore phenotype, upon the genotype of the individual ascospore. No evidence was found that the white ascospores were due to chromosomal rearrangements. No separation of the perithecial and ascospore phenotypes by recombination was observed in a cross between one of the mutants and a per-1+ strain. However, apparent low levels of recombination in crosses between some of the mutants indicated possible genetic complexity at the per-1 locus. The phase specificity of the per-1 mutations and the possible nature and mode of expression of the orange and yellow perithecial pigments are discussed.


Selection of extranuclear mutants of Neurospora crassa. A procedure is described that produce primarily extranuclear mutants, of Neurospora carassa. An analysis of five mutants. [cni-3], [rsp-2], [rsp-3], E1RSP-4], IS PRESENTED. All five mutants segregate in an extranuclear manner. They can be assorted into two classes based on their respiratory properties: (1) those with cyanide-insensitive respiration (cni); (2) those with slow respiration (rsp). All of the mutants are female sterile. The respiratory trait can be placed in different nuclear backgrounds by heterokarytoic transfer. The abnormal respiratory traits are observed in mitochondria isloated from the mutants and it is likely that the mutations are in mitochondrial DNA.


[A neurogenetic study in an inbred population]. A Tatar family from a semi-isolated village in the Gorky Region is described in which a neurological and ophthalmological syndrome was inherited. In homozygotes this syndrome comprised the degeneration of subcortical cerebral ganglia (hyperkinesis), nystagmus, oligophrenia and a peculiar variant of tapetoretinal degeneration. Heterozygotes exhibited ophthalmological abnormalities, such as the similar defects of eye bottom and nystagmus. The two homozygotes observed were sibs derived from a marriage between first cousins. Five more families with other rare hereditary anomalies (both dominant and  recessive) were discovered in this village. The total inbreeding coefficient in the village was found to be 0.0075. The high degree of inbreeding, subisolation and high fertility are regarded as factors favorable for the distribution of rare deleterious mutations due to the founder-effect.


[Multiple birth and Down's disease].

[Multiple birth and Down's disease]. The frequency of twinning among newborns with Down's syndrome (2,11+/-0,6%)was significantly higher than in the general populaltion (0,73+/-0,3%). The increase in the rate of multiple births of children with trisomy-21 occurred due to almost three-fold excess in the frequency of dizygotic (discordant) twin pairs over the expected level. The increase in the frequency of dizygotic twins with Down's syndrome was explained by the combined effect of two independent factors: the increase in probability of dizgotic twins natality and the enhanced rate of children birth with trisomy-21, which depended on the increase in mother's age.


[Anomalies in the karyotypes of premature children]. A cytogenetic investigation of two groups of prematurely born babies was carried out on the basis of the specialized department for prematurely born children in Moscow and in the Moscow Region. The material for this investigation was the culture of lymphocytes. In the first group comprising 607 prematurely born babies without any perceptible developmental defects abnormalities of the karyotype were observed in 15 probands (2.5%) which is 3.5 times higher than the frequency of karyotypic abnormalities among newborn babies from the same population born in proper time. In the second group comprising 70 prematurely born babies with various congenital malformations various karyotypic abnormalities were observed in 13 probands (18,6%), which is 8 times the frequency among babies from the same population born in proper time. The main type of abnormalities observed were those affecting the system of sex chromosomes and the cases of trisomy of the 21st pair of autosomes and structural abnormalities. The high proportion of X- and 21-trisomies among the chromosome abnormalities observed suggests their important role in the etiology of premature births and postnatal death-rate of mutant organisms having D- and E-trisomies and structurally unbalanced chromosomal aberrations.


[A medico-genetic study of isolates in Uzbekistan. III. Results of a cytogenetic study]. The cytogenetic examination of the population of the villages of Karakent and Ishan consisted of two directions: the study on the frequency of chromosome aberrations in the culture of lymphocytes and the diagnostics of anomalies and variants of karyotype. The frequency of chromosome aberrations of 40 individuals was studied. It is shown that the frequency of cells with chromosome aberrations of the individuals in different villages does not differ and on the average is 1,4%. The distribution of lymphocyte culture according to the number of aberrations corresponds to that of theoretical Puassonian. Chromatide breaks are the main type of the aberrations. Among 250 karyotypically examined individuals no evident structure reformations were found. In the caryotype of a 7-year old girl trisomia of the 21st autosome was detected. On the basis of differential staining of chromosomes by Hiemse's dye 18 individuals (7,2%) were diagnosed to have insignificant changes in morphology of some chromosomes, considered as variants of caryotype. In the majority of cases these changes were of a family nature. On the medical examination mnay individuals were diagnosed to have different pathological features, though we did not succeed in revealing any correlation between a certain microanomaly of chromosomes and a pathological feature.


[Several demographic indices of isolated populations in Uzbekistan]. Demographic indices of isolated populations with high level of inbreeding are calculated. Demographic date within each population are given separately both for inbred families and for outbred ones. The data obtained revealed the higher frequency of life-born children in outbred families and significantly higher frequency of still-born in inbred ones, the frequencies of twin births being nearly the same in inbred families and in outbred ones. It should be mentioned that more boys were born in inbred families in comparison with outbred ones. Dimensions of genetic isolates are also calculated for each of above mentioned isolated groups.


[Dermatoglyphics of the relatives of children with congenital defects in development]. The localization of an axial triradius and the flexor creases were studied in 173 phenotypically normal mothers and 104 fathers of congenitally malformed children. The most pronounced changes ofdermatoglyphics were found in the parents of children with polygenic determined defects, less pronounced ones-- in the parents of children with multiple congenital non-chromosomal defects and with Down's syndrome. The frequency of the pathological features studied was similar both in children with polygenically determined isolated defects and with Down's syndrome. The frequency of the pathological determined isolated defects and in their parents. In multiple congenital defects and in Down's syndrome the abnormalities ofof the localization of an axial triradius and of the flexor creases were found in children more frequently than in the parents. It is suggested that the above mentioned peculiarities of parental dermatoglyphics may be useful for the genetic counsleling.


[Inbreeding in the Samarkand region].

[Inbreeding in the Samarkand region]. Data on the frequency of inbreeding in some isolated populations of Samarkand region are given. Statistically significant differences were established in the frequency of inbreeding in separate groups and in the general population of the region. Inbreeding marriages were more observed between paralel cousins, occasionally they were made between secon cousins. Strict time dependence of inbreeding frequency was not found, but it was noticed that the level of inbreeding was reduced since 1930 to 1949.


[Frequency of genes and blood groups of the systems, ABO, MN, Rh and P among the Belerussians and Poles of the Grodno region]. A distribution of the gene frequencies and blood groups of the ABO, Rh, NM and P system in the poles and the byelorussians inthe Grodno region is investigated. The following frequencies of genes in the byelorussians were revealed: r(O)--0,6210; P(A)--0,2451; Q(B)--0,1339; D--0,6093; D-9,3907; M-0,6063; N-0,3937; P(+)-0,4971; P(--)--0,5029; and in poles: r(O)--0,6284; p(A)--0,2353; q(B)--0,1363; D - 0,6065; d - 0,3935; M - 0,6093; N- 0,0397; P(+) -0,4966; P(-) -0,5034. No statistically reliable differences were revealed in frequencies of the alleles an d phenotypes of the investigated systems in the poles and byelorussians. By comparison of the same isoantigen systems of the byelorussians in the Grodno region with the common population of the byelorussians in the BSSR it was found that statistically significant differences do not exist. The comparison of the poles in the Grodno region withthe poles in the Polish People's Republic showed a statistically reliable difference of their genofunds in terms of the gene frequencies: r(O) , p(A), D, d, P(+), P(-). This confirms the hypothesis about an indigenous origin of the poles in the Grondno region.


[Inbreeding characteristics of thepopulation and the distribution of schizophrenia in one of the rural regions of Azerbaijan]. The investigation was carried out in Pushkin region of Azerbaijan SSR. The coefficient of inbreeding was found to be 0,01142 in 2 typical villages; the frequency of consanguineaous marriage in both villages was 30+. The occurence of consanguineous marriage is explained by a little migration of the population, large families and a stability of marriage traditions. An increased frequency of parental consanguinities of sporadic schizophrenic patients in comparison with the average one was found. This indicates the determination of some cases by rare recessive genes.


[A medico-genetic study of the population of Western Pamir. IV, Several hereditary neuropsychiatric diseases among the population of the Bartang canyon]. On the basis of clinico-genealogical investigation of the population of some small villages in the ravine Bartang--the isolate in high-montane region--the following indices of frequency of some psychiatric disorders were determined: olygophrenia--3,96; epilepsy--5,09; schizophrenia--6,78 for a 1000 of population. These indices do not differ significantly from those for other regions of the USSR. The favourable evolution of epilepsy and schizophrenia and the absence of genetic froms of olygophrenia were marked.


Ageing changes in mammalian skeletal muscle: biochemical studies. In the course of ageing, biochemical characteristics of mammalian skeletal muscle are shown to become altered mainly within the system of energy metabolism. The enzymatic behaviour of myofibrillar proteins remains virtually unchanged throughout life, but a gradual loss of fibres causes a decrease in musculae strength. Working capacity, however, in terms of prolonged muscular work is considerably reduced with age, because of a less efficient energy metabolism. Enzymes, particularly of the Krebs cycle, show diminished specific activities, and consequently, ATP and phosphocreatine concentrations are lowered. Possible primary and secondary factors responsible for these changes are discussed.


Alcohol and absorption from the small intestine. 2. Effect of ethanol on ATP and ATPase activities in guinea-pig jejunum. After the exposure of isolated segments of guinea-pig jejunum to 2% ethanol for one hour, a significant reduction (P less than 0-001) in the adenosine triphosphate content (ATP) was observed when compared with levels found in segments perfused with Krebs' solution. However, no alteration was noted in the activity of adenosine triphosphatase (ATPase). The chronic administration of 50% ethanol in a dose of 2-5 g/kg for two weeks did not affect either the ATP content or ATPase activity in jejunal mucosa.


Mechanism of thrombocytopenia induced in mice by anti-platelet serum. Although anti-platelet serum is frequently used to produce thrombocytopenia, the mechanism of how platelets are removed from the circulation is poorly understood. In vitro studies indicated that anti-platelet serum caused platelet aggregation, whereas normal rabbit serum did not. The aggregation was dose related; at the lower dose, aggregated platelets were shown to deaggregate and platelets released from the aggregates responded normally to ADP but not to collagen. In mice whose platelets were previously labeled with Na235SO4, anti-platelet serum caused an increase in the amount of 35S mucopolysaccharides (MPS) recovered from the kidneys. No increase in radioactivity was found in the lungs, livers, or spleens of similarly treated mice. The data suggest that platelet specific anti-serum causes platelets to aggregate leading to ADP (and consequently 35S-MPS) release; the accumulation of 35S in kidneys may be due to removal of MPS and/or platelets from the circulation.


[Pharmaco-angiography with angiotensin (author's transl)]. The results of pharmacoangiography using angiotensin were compared with the findings in 101 patients during selective angiography of the kidneys (48 cases), the pancreas and liver (46 cases) and of peripheral soft tissue lesions (7 cases). Angiotensin in a dose of 0.5--l mug (renal artery), 1--5 mug (coeliac artery) and 5--10 mug (peripheral vessels) was found to be a constant and potent vaso-constrictor in 99% of cases. Intraarterial injection of angiotensin improved evaluation in 18 out of 27 cases (66%) with a final diagnosis of a tumor, in 18 out of 22 patients (77%) with cysts and in 16 out of 24 (66%) with an inflammatory process. In three out of 27 cases (11%) an angiographic diagnosis was possible only after using pharmacoangiography. The use of angiotensin represents a valuable possibility of clarifying otherwise uncertain angiographic diagnoses. This is particularly the case where superselective catheterisation is impossible.


[The pancreatographic effect during pharmacoangiography of the pancreas following the administration of glucagon (author's transl)]. Angiography before and after the administration of Glucagon was performed in 33 adult patients with symptoms suggesting a pancreatic lesion. Preferently the pancreatographic effect was evaluated. The results were compared with those of the angiography following the administration of Secretin and Tolazoline. The pancreatographic effect was visualized in 70% of the patients examined with Glucagon and the rate of visualization of the effect with Secretin and Tolazoline was 60% and 74.5% respectively. The representation of the small vessels could be enhanced with Glugacon only in 15% for the arteries and in 12.5% for the veins, whereas using Secretin and Tolazoline the improvement raised up to 78% of the cases. -- The pancreatographic effect as an additional sign is useful in the differential diagnosis of the chronic pancreatitis (mottled) and the carcinoma of the pancreas (defect or absence of the effect).-- The superselective technique is recommendable. Using this method an improvement of the pancreatographic effect can be achieved already. In pharmacoangiography Tolazoline gives better results than Glucagon.


[Angiography in biliary neoplasia (author's transl)]. The angiographic appearances of biliary neoplasms and their differential diagnosis is discussed in relation to 15 patients with annular carcinomas of the gall bladder or bile ducts. The outstanding angiographic features of biliary carcinomas are irregularities of the arterial contours and vascular occlusion, followed in importance by neo-vascularity of the malignant tumour.


[Animal experiments on the distribution and excretion of an intravenously injected biliary contrast medium (Ioglycomate) (author's transl)]. The distribution and excretion of an intravenously injected, radioactive biliary contrast medium (Ioglycomate) were studied in the mini-pig after the induction of choledochal, thoracic duct and gall bladder fistulae. The investigations were carried out with free lymph and bile flow during artificial cholestasis and after occluding both ureters. Following intravenous injection of 0.24 to 1.0 ml. Bilivistan, there was a cholersis up to six times original value. Ther thoracic duct lymph showed only a small volume rise. The lymphatic circulation played no significant quantitative role in contrast distribution of Ioglycomate in the animal, nor did it influence the blood clearance curves. During normal bile flow, only 1.3% of the injected dose appeared in the thoracic duct within three hours, and during acute biliary obstruction, only 2.6%. The investigations have indicated a biliary transport maximum Ioglycomate in the mini-pig of 2.9 mg./min./kg. body weight. If the excretory capacity of the liver is exceeded and during cholestasis there is compensatory excretion of the biliary contrast medium through the kidneys.


[A comment on the article by Taenzer, V., et al.: Intravenous cholegraphy with Chologram(R), Fortschr. Röntgenstr. 123 (1975) 414]. A comparison of the results published by Taenzer et al. shows: 1. The contrast value of the new hepatotropic substance Iotroxamid (Chologram) in man is of the same order as the previously available contrast media Bilivistan and Biligram (Ioglycamide) 2. The reputedly improved tolerance of the new substance should be confirmed in a more extensive clinical material under the stated conditions. 3. The question whether Chologram permits greater flexibility with regard to the timing of the examination must also remain open for the present.


[The accuracy of radiological and endoscopic examinations in the diagnosis of carcinoma of the stomach (author's transl)]. The accuracy of radiology in the diagnosis of gastric carcinomas was checked on 232 cases, including 24 early examples. Accuracy depends most of all on the experience of the radiologist. Amongst 146 patients, using a satisfactory technique, a carcinoma was diagnosed in 131 patients (90%) and suspected in eight (6%). In five (3%) the changes were misinterpreted as being benign and the lesion was missed in two (1%). Of 120 gastric carcinomas submitted to operation a correct diagnosis had been made radiologically in 88% and suspected in 4%; endoscopically, the diagnosis was made in 92% and suspected in 2%. Of the 24 early carcinomas, both methods suggested the presence of a malignant lesion in 80%. The combination of radiology, endoscopy, hitology and cytology increases accuracy to 95%. These results indicated that localised changes in the gastric mucosa and the wall of the stomach can be demonstrated only by using refined radiological techniques; each lesion should be confirmed by endoscopy and histology.


[The "bagpipe" stomach, a form of organ neurosis (author's transl)]. A form of gastric neurosis is described consisting of continuous borborigmy associated with a spastic hour-glass stomach. The phenomenon has been called the "bagpipe" stomach.


[Functional gastric diagnosis (author's transl)]. A method is described (isotope gastro-diagram) in which a radio-active labelled standard meal is used under physiological and phatological conditions; in this way the half-value time of gastric emptying can be used as an objective measure of gastric motor function, and which can be easily reproduced. This has become of clinical interest, particularly since the introduction of hypotonic and double contrast methods in radiological diagnosis. The clinical value of this method has been elucidated amongst surgical patients on whom pre- and post-operative measurements were carried out following selective vagotomies, combined with various types of pyloroplastry for the treatment of gastric and duodenal ulcers.


[The angiographic investigation of duodenal tumours (author's transl)]. The diagnosis and differential diagnosis of primary duodenal carcinomas by conventional radiological methods is difficult. Valuable information can be obtained by angiography, since primary duodenal carcinomas, unlike carcinomas of the papilla and pancreas, are characterised by the formation of pathological vessels arising from the duodenal branches of the gastro-duodenal artery. The integrity of the latter is an important differentiating feature. Exact localisation of the tumour is important in pre-operative assessment and diagnosis.


[Angiography of carcinomas of the renal pelvis (author's transl)]. The angiographic criteria of 19 renal pelvic carcinomas were analysed. Two groups of signs, direct and indirect, could be detected. Of 19 histologically proved cases of renal pelvic carcinomas, the diagnosis had not been made angiographically in the case of a small tumor, which was 11 mm in diameter. The usefulness of preoperative angiography for diagnosis and operative planning is emphasized.


[The vascular supply congenital high renal ectopia (author's transl)]. The angiographic findings in two cases of congenital high renal ectopia are described. Elongation and straightening of the renal arteries, pre-renal branching, transverse or inverted position and typical deformity of the kidneys make up the anatomical components of this anomaly. The previously held view of high origin of the renal vessels has not been confirmed. High origin of the renal arteries from the abdominal aorta does not distinguish congenital from acquired renal ectopia, as may occur after trauma.


[A urologic-radiological view of perinephric abscesses (author's transl)]. Perinephric abscess is a rare condition; it may be acute, but can take a chronic and atypical course as a result of incomplete treatment with antibiotics. In this case the diagnosis is often delayed. The most common cause is primary renal disease, with perforating ureteric stones, abscess-forming pyelonephritis, renal carbuncle and pyonephrosis as the most important factors. Diagnosis depends on a varying combination of clinical signs, any of which is not necessarily present and which is not pathognomic, but nevertheless, in their totality, are fairly typical. Characteristic are pain on percussion and pressure, resistance in the renal angle and fever. Laboratory investigations do not contribute to the diagnosis. These only show findings typical of any infection, and frequently a marked anaemia. An infected urine may be suggestive. The traditional clinical and radiological methods may well indicate a space-occupying lesion, but its further elucidation depends on angiography. Renal and perinephric abscesses must be distinguished from other space-occupying renal lesions. Abscesses can usually be distinguished from cysts because they are generally less clearly demarkated and often show a hypervascular margin with a "blush". A further differential diagnosis of perinephic abscess is a peri-renal haematoma. Radiologically, an haematoma also produces a perirenal mass with displacement and compression of the kidney. As with perinephric abscesses, the angiogram shows dilatation and displacement of the capsular arteries. Differences in the neovascularity, as well as in the clinical symptoms, permit differentiation between abscesses and hypovascular carcinomas in most cases, or at least suggest the probable diagnosis.


[Extraperitoneal endometriosis in a kidney (author's transl)]. A case of extraperitoneal, isolated, intrarenal endometriosis observed by the author is described. The diagnostic problems are discussed; usually these concern complaints related to menstruation.


[Urethro-cysto-colpo-rectography, a radiological method for the diagnosis of insufficiency of the pelvic floor (author's transl)]. Contrast examination of pelvic organs was carried out in 200 female patients with insufficiency of the pelvic floor. The topography of the organs in the true pelvis and their functional relation was recorded on full-size film and 70 mm. roll film. Radiological examination provides more accurate indications for plastic surgery of the pelvic floor, influences the operative procedures and permits better evaluation of operative results.


[The results of galactography -- a contribution to the early diagnosis of carcinoma of the breast (author's transl)]. Excision of lactiferous ducts was carried out in 67 patients out of a total of 231 on whom galactography had been performed. Criteria for excision were destruction of the duct, its occlusion, irregularities of contour and leak of contrast on the galactogram. Histological examination demonstrated a carcinoma in 24 patients. In only one patient were there axillary node metastases where no tumour was palpable. Galactography is an important method for the early diagnosis of breast carcinomas in lactiferous ducts.


["Numeric increase of microcalcifications, an important radiologic sign of occult breast cancer" (author's transl)]. An increase in the number or the sudden appearance of multiple microcalcifications in the course of a mammographic controls series represent a further important sign of malignancy. In 14 of our cases witha non palpable breast cancer we were able to observe an increase in the number or a sudden appearance of typical calcium precipitates during an observation period, which, according to the case, lasted from 6 to 21 months. Biopsy revealed in all cases an early cancer. Our observations demonstrate the absolute indication for biopsy in all patients, which during a mammographic control series suddenly present microcalcifications, or an increase in the number of the ones that were previously observed. All patients showing clustered microcalcifications, which because of their small number are not demanding a biopsy, should be regarded as risk-cases and observed regularly in order to rule out or demonstrate an increase in the number of calcifications. Follow-up series within six months are recommended.


[Dacrocystography. Paper I: A simplified catheter technique (author's transl)]. By using a PE-catheter for catheterising the tear ducts, dacrocystography becomes a simple and rapid investigation. It permits excellent morphological demonstration of pathological changes, since films can be obtained under screening control. A water-soluble, low viscosity contrast medium is recommended. Amongst more than 100 dacrocystograms, there were no serious complications.


Studies on delayed hypersensitivity pleural exudates in guinea pigs. I. Demonstration of substances in the cell-free exudate which cause inhibition of mononuclear cell migration in vitro. Leucocyte migration inhibitory (MI) activity was investigated in vitro in the delayed hypersensitivity reaction induced by intrapleural injection of PPD into FCA-sensitized guinea-pigs. During the initial reaction (6 h) two types of antigen-dependent MI activity were detected in serum and cell-free exudate. One was of high molecular weight and associated with immunoglobulin and the other was of low molecular weight and appeared to be related to so-called "antigen-dependent MIF". As the reaction progressed (i.e. 12-24 h), two types of antigen-dependent MI activity were revealed in exudate, but not in serum. One was high molecular weight and the other was low molecular weight and thought to be related to so-called "antigen-independent MIF". Similar experiments were performed on the reverse passive Arthus reaction in the pleural cavity of guinea-pigs. A high molecular weight MI activity was detected in 6-h cell-free exudate and was found to be antigen-independent. "So-called MIF" was not found in this reaction.


Studies on delayed hypersensitivity pleural exudates in guinea-pigs. II. The interrelationship of monocytic and lymphocytic cells with respect to migration activity. The in vitro migration activity of monocytic cells and the effect of lymphocytes in the delayed hypersensitivity (DH) reaction induced by intrapleural injection of PPD into FCA-sensitized guinea-pigs was investigated. The in vitro migration of exudate mononuclear cells was lower than that of comparable blood cells, and continued to decrease as the reaction progressed. An inverse relaationship was observed between the migration area and cell volume of mononuclear cells from both blood and exudate. Similar experiments were performed on the reversed passive Arthus (RPA) reaction in the pleural cavity of guinea-pigs. For 6-h exudate, the mononuclear cell migration exceeded that for blood mononuclear cells. However, the migration of mononuclear cells from 18-h exudates was markedly reduced. As with DH, an inverse relationship between the migration area and cell volume was observed with the mononuclear cells of RPA exudates. Following the addition of antigen, the migration of DH exudate mononuclear cells was inhibited whereas the exudate mononuclear cells of the RPA reaction remained unaffected. For DH, the inhibition of migration induced by antigen appeared to be related to the non-adherent cells of 6-h exudates, and both the adherent and non-adherent cells of 18-h exudates.


The natural mediator for PMN emigration in inflammation. VIII. Production of leucoegresin-like chemotactic factor in reversed passive Arthus reactions in rats. The mediation of tissue neutrophilia in the reversed passive Arthus reactions in rats was studied on extract from the skin lesions. Approximately 55 per cent of the neutrophil chemotactic activity in the reactions exhibiting a maximal tissue neutrophilia seemed to be associated with a leucoeresin-like chemotactic factor which can be absorbed by an immunoadsorbent chromatography with anti-rat IgG antibody. On the other hand, the neutrophil chemotactic activity, comparable to most of the remaining chemotactic activity, was reduced in complement-depleted conditions in which the intensity of tissue neutrophilia in the reactions was moderately decreased, suggesting a possible involvement of complement-derived chemotactic factors.


Characterization of a T-lymphocyte inhibitor in the serum of tumour-bearing mice. Sera from mice with large tumours from a variety of tissue types and sources have been shown to contain substances capable of suppressing the proliferative response of normal mouse lymphocytes to concanavalin A (Con A), bacterial endotoxin (LPS) and allogeneic cells. The present paper deals with studies on the nature of these inhibitory materials using mainly a methylcholanthrene-induced rhabdomyosarcoma in DBA/2J mice. It was found that a material responsible for inhibition of the Con A response eluted with immunoglobulins on Sephadex G-150 and eluted with monomeric immunoglobulin on Sephadex G-200. The component of tumour-bearer serum responsible for the suppression of the LPS response of normal lymphocytes eluted from Sephadex G-150 with the alpha and beta globulins and albumin (molecular weight less than 150,000). The immunoglobulin-containing serum fraction from tumour-bearing animals inhibited the mixed lymphocyte response, Con A response, and specific immune response to purified protein derivative (PPD) in allogeneic cell systems. It also inhibited the in vitro primary response of mouse cells to sheep red blood cells, and, to a lesser extent, the response to a T cell-independent antigen (DNP-dextran). The inhibitory activity continued to elute with monomeric IgG on Sephadex G-200 when columns were run in 1640 medium and adjusted to pH 2-5, indicating that an acid dissociable complex was not responsible for inhibitory activity. Inhibitor activity could be removed by absorption on immuno-adsorbents containing goat anti-mouse immuno-globulin, and could be recovered by acid elution from the absorbent. Inhibitor activity was not removed by immunoadsorption on columns prepared with antisera to chicken immunoglobulin.


Immune mechanism in Pasteurella multocida-infected mice. Various immunizing procedures were tested for their effect on the growth of Pasteurella multocida in specific pathogen-free CD-1 mice. Two injections with killed vaccine incorporated into Freund complete adjuvant gave excellent protection against parenteral challenge, but less to control the growth of an aerogenic inoculum. Protection with adjuvant-treated preparation was always superior to that seen with non-adjuvant-treated vaccines. A killed saline-suspended vaccine introduced aerogenically marginally increased resistance to small (2 to 5 mean lethal doses) aerogenic challenges. Live mycobacterium bovis (BCG) vaccine immunopotentiated a single dose of heat-killed P. multocida vaccine in terms of the protective immune response against a subsequent footpad challenge. Hyperimmune mouse serum, administered intraperitoneally, intramuscularly, or intravenously 1 to 7 days prior to subcutaneous challenge with 500 to 5,000 P. multocida, was highly protective. Mice injected in the thigh with 0.2 ml of hyperimmune serum prior to footpad challenge frequently developed a severe inflammatory response with local swelling within 48 h; these lesions often became severly abscessed with time. The passively protected, footpad-infected mice developed active immunity against a subsequent challenge given into the opposite footpad.


The induction of acute and chronic cardiovascular disease in animals by psychosocial stimulation. It has been established that sustained emotional arousal can accompany the psychosocial stimulation induced by the social interaction of members of a social group as they compete for desiderata, such as food and water. This paper reviews the evidence that this arousal of neuronendocrine response patterns can, in turn, lead to disease states and to a fatal outcome. Various experimental observations in pigs, monkeys, baboons, tree shrews, and rodents demonstrate both acute and chronic disturbances of cardiovascular function. These conditions can lead to sudden death or to sustained high blood pressure with arteriosclerotic lesions in the heart and blood vessels. It is shown that when social pressure that has been maintained for a sufficiently long period is relieved, the organism does not revert to normal.


Psychophysiologic disorders in children and adolescents. Psychosomatic disorders in children and and adolescents is a topic that covers a wide variety of illnesses and one which is difficult if not impossible to define accurately. In general, chronic emotional states, often nonspecific, serve as strong contributors to the development of a physical illness. The particular illness is often dictated by varying degrees of biological predisposition in one physiological system-i.e., such a predisposition in the respiratory system may lead to asthma or in the gastrointestinal system to ulcerative colitis. In some cases the biological factor is large and the emotional factor minimal, while in other cases the reverse is true. In the early days of research in psychosomatic disorders it was widely believed that each disorder was accompanied by certain specific emotional problems. Further study has shown this is not true. It was also felt that many, if not most of these disorders could be cured by psychotherapy, and this also has proven to be a fallacy. we have moved more and more to the team approach. Since both psyche and soma are involved, more than one specialist is usually required. In children and adolescents this may involve a child psychiatrist, a pediatrician, an allergist or gastroenterologist, a social worker and a psychologist. It requires time and patience to form an effective and smoothly functioning team in which all members respect one another's potential contribution. Some examples of team operation are presented and some of the problems outlined. In addition, there is attention given to the special problems of the adolescent and also the child with chronic nonspecific physical complaints as well as the child who requires hospitalization.


Diagnosis and management of herpes simplex ocular infection. The multifaceted nature of ocular herpes simplex has become more clearly defined in recent years, as it has become apparent that it is a disease characterized by both infectious and immune components. Therapy Therapy of infectious epithelial dendritic-geographic disease is generally gentle debridement of the ulcer followed by antimetabolite chemotherapy with IDU or Ara A. Tropic (metaherpetic) ulceration may occur postinfection and is caused by sterile basement membrane damage, which makes it difficult for the epithelium to heal across the damaged ulcer base. Therapy is generally that of recurrent erosion and involves patching, soft contact lenses, and lubricating drops and ointments. Stromal disease may be (1) viral interstitial keratitis, which is slowly responsive to antiviral therapy, or (2) immune disciform reaction, which may or (hopefully) may not necessitate steroid therapy with prophylactic antiviral and antibiotic cover. Herpetic iritis may occur alone or with any form of corneal disease. While it is generally felt to be caused by intact intraocular virus, therapy is still steroid-oriented for lack of more effective and penetrating antiviral drugs. Antimetabolite-induced medicamentosa may mimic almost any form of herpetic disease and should be ruled out in any differential diagnosis of a patient deteriorating under therapy.


Ca2+-sensitivity of actomyosin ATPase purified from Physarum polycephalum. A contractile protein closely resembling natural actomyosin (myosin B) of rabbit skeletal muscle was extracted from plasmodia of the slime mold, Physarum polycephalum, by protecting the SH-groups with beta-mercaptoethanol or dithiothreitol. Superprecipitation of the protein induced by Mg2+-ATP at low ionic strength was observed only in the presence of very low concentrations of free Ca2+ ions, and the Mg2+-ATPase [EC 3.6.1.3] reaction was activated 2- to 6-fold by 1 muM of free Ca2+ ions. Crude myosin and actin fractions were separated by centrifuging plasmodium myosin B in the presence of Mg2+-PPi at high ionic strength. The crude myosin showed both EDTA- and Ca2+-activated ATPase activities. The Mg2+-ATPase activity of crude myosin from plasmodia was markedly activated by the addition of pure F-actin from rabbit skeletal muscle. Addition of the F-action-regulatory protein complex prepared from rabbit skeletal muscle as well as the actin fraction of plasmodium caused the same degree of activation as the addition of pure F-actin only in the presence of very low concentrations of Ca2+ ion


Physarum tropomyosin-troponin complex. Isolation and properties. The relaxing protein (TM-TN complex) was isolated from plasmodia of Physarum. SDS-gel electrophoresis revealed that the relaxing protein consists of tropomyosin subunits with a molecular weight of 35,000 troponin subunits with molecular weights of 38,000 (T) and 24,000 (I) and several other components. No component corresponding to muscle troponinC (MW-18,000) was detected in the plasmodium relaxing protein. The relaxing protein combined with muscle F-actin, and inhibited the ATPase [EC 3.6.1.3] activity and superprecipitation of reconstituted muscle actomysin in the absence of Ca2+ ions. The inhibition was reversed by adding 1 muM Ca2+ ions.


Effects of deuterium oxide on elementary steps in the ATPase reaction. Evidence for the similarity of key intermediates in contractile and transport ATPase. The effects of D2O on the elementary steps in the contractile and transport ATPase [EC 3.6.1.3] reactions were studied, and the following results were obtained: 1. The rate of H-meromyosin ATPase in the steady state decreased in D2O to 60% of that in H2O. Deuterium oxide did not affect the size or rate of the initial burst of Pi liberation, i.e. the amount or rate of formation of the reactive myosin-phosphate-ADP complex, MADPP. Moreover, neither the rate of change in the fluorescence spectrum of H-meromyosin induced by ATP (the rate of formation of the second enzyme-ATP complex, M2ATP) nor the rate constant of decomposition of MADPP into M degrees + ADP + Pi was affected by D2O. However, the equilibrium constant of the step M2ATP in equilibrium MADPP decreased in D2O to about 1/2 the value in H2O. 2. In the case of the Na+-K+-dependent ATPase reactin, neither the rate constant of formation of the second enzyme-ATP complex, E2ATP, nor that of decomposition of a phosphorylated intermediate, EADP approximately P, was affected by D2O. However, the equilibrium constant of the step E2ATP in equilibrium EADP approximately P decreased in D2O to about 1/2.5-1/4 of the value in H2O. These results suggest a similarity between the modes of binding of phosphate in MADPP in the myosin ATPase reaction and in EADP approximatley P in the Na+-K+-dependent ATPase reaction.