Activities of dichlorvos or disophenol against the hookworm (Uncinaria lucasi) and sucking lice of northern fur seal pups (Callorhinus ursinus) on St. Paul Island, Alaska. One controlled and six critical tests were conducted in July, 1977 with northern fur seal pups (Callorhinus ursinus) to determine the efficacies of a single dose of dichlorvos capsules at 29.3 to 32.8 mg/kg, tablets at 10.5 to 11.5 mg/kg, or disophenol at 9.9 mg/kg given subcutaneously against natural infections of adult Uncinaria lucasi. In the controlled test, 20 pups were treated and 10 pups were nontreated. Removal of hookworms in this test was 99% for five pups receiving dichlorvos capsules, 99% for five pups receiving dichlorvos tablets, and 77% for 10 pups receiving disophenol. Also, both formulations of dichlorvos and the formulation of disophenol were highly active against natural infestations of two species of sucking lice (Proechinophthirus fluctus and Antarctopthirus callorhini). In critical tests with four pups treated with dichlorvos capsules at 28.6 to 30.6 mg/kg, removal of hookworms was uniformly 100%. Disophenol at 9.9 mg/kg removed 100% and less than 1% of hookworms in two pups, respectively, in critical tests.


Normal fasting plasma glucose levels in some birds of prey. Blood samples taken from five great horned owls (Bubo virginianus), eight red-tailed hawks (Buteo jamaicensis), four marsh hawks (Circus cyaneus), two prairie falcons (Falco mexicanus), five golden eagles (Aquila chrysaetos), and five white leghorn chickens (Gallus domesticus) that had been fasted for 24 h were used to determine plasma levels of glucose by the glucose oxidase method. The mean plasma glucose levels were: great horned owls 374.6 mg/100 ml, red-tailed hawks 346.5 mg/00 ml, marsh hawks 369.3 mg/100 ml, prairie falcons 414.5 mg/100 ml, golden eagles 368.4 mg/100 ml, and white Leghorn chickens 218.2 mg/100 ml. The plasma glucose levels obtained for the raptorial birds in this study were considerably higher than those found for the chickens. These values are discussed in relation to the carnivorous food habits of raptors.


Rabies antibody prevalence and virus tissue tropism in wild carnivores in Virginia. Carnivores trapped in a rabies control program in Virginia were examined for rabies virus and serum neutralizing antibody. Local antibody prevalence ranged from 0% to 29% in gray foxes (Urocyon cinereoargenteus). Rabies virus was pantropic in naturally infected gray foxes and a bobcat (Lynx rufus).


Serologic and hematologic values of bison in Colorado. Recent economic and aesthetic interest in North American bison (Bison bison) has lead to increased interstate transport of these animals. Serologic and hematologic standards for bison are needed to detect disease in transported animals as well as within herds. This paper describes variation in blood physiological parameters in bison caused by variations in diet and season. Blood was taken from six bison and analyzed for serologic and hematologic parameters. Significant variation was found in blood urea nitrogen, chloride, cholesterol, creatinine, eosinophil, glucose, hemoglobin, lactic dehydrogenase, leukocyte, packed cell volume, potassium, serum globulin, serum glutamic oxalacetic transaminase, SGPT, and sodium levels between animals receiving a high energy-high nitrogen diet and animals receiving a low energy-low nitrogen diet.


Anesthesia in the coyote using a combination of ketamine and xylazine. Ketamine and xylazine were combined to provide anesthesia for coyotes. The drugs were tested in eight adult animals divided equally by sex. A dosage combining 5.5 mg./kg. of each drug provided effective anesthesia for periods from 45 to 60 min.


Methoxyflurane anesthesia in mule deer (Odocoileus hemionus) fawns. Methoxyflurane inhalation was used a total of 58 times to anesthetize 23 hand-reared mule deer (Odocoileus hemionus) fawns ranging from 25 to 85 days of age. Induction, maintenance, and recovery times were recorded for 28 anesthetizations. Induction time was unrelated to age and averaged 3 +/- 1 min (X +/- SD). Recovery time was longest in the youngest fawns and varied with the depth but not with the length of anesthesia. Induction and recovery were smooth, the depth of anesthesia was easily controlled, and analgesia and muscle relaxation was excellent. No adverse effects or complications were encountered.


[Dose-response relationships at different exposure levels. Re-examination in establishing no-effect levels (author's transl)]. In this study dose-response and dose-effect relationships were examined with reference to no-effect levels using observed data from three groups of lead workers who had been exposed to three different concentrations of lead. Blood lead concentration (PbB) was used for "dose" and ALA concentration in urine (ALAU) and rate for 5 mg/l or greater of ALAU were used as "effect" and "response" respectively. Dose-effect and dose-response relationships between PbB and ALAU of these three different exposure populations indicated three different curves although theoretically they should all have indicated a similar curve. This means that "effect" or "response" for the highest exposure group was higher than that for the lowest exposure group on the same "dose" level. This difference is statistically explained for the most part by variations in the determinations of "dose" (PbB) as well as "effect" or "response" (ALAU). In view of the above results, it would seem that re-examination is required in establishing criteria of no-effect levels for dose-response relationships of various environmental chemicals.


The chemical receptive mechanism in the lateral-line organ. Stimulating effects of various mono- and divalent cations on the lateral-line organ were theoretically analysed by use of the site binding chemical adsorption model with the principle of "hard and soft acids and bases." A linear relation between the softness parameter and the logarithmic value of the intrinsic association constant was obtained for the cations of Na, K, Tl, Ag, Ca, Mg, and Cd. The order of effectiveness of these cations agreed with that of the intrinsic association constant. Using these values for various cations, the critical concentration of divalent cations necessary to supress the effect of monovalent cations was calculated and compared with the experimental values. The calculated concentration of the hard divalent cations (Ca2+, Mg2+), which suppressed the effect of the hard monovalent cations (K+, Na+), agreed with the experimental concentration. The same relations were obtained between the suppressive effect of a soft divalent and a soft monovalent cation. The chemical adsorption of Ag+ on the lateral-line organ of Xenopus laevis was investigated by using a transmission electron microscope equipped with an X-ray microprobe analyser in order to get further confirmation of this model. Silver applied to the lateral-line organ was found around a kinocilium but not in the hair cells of the lateral-line organ. Thus chemical adsorption of the cation on the surface of the receptor membrane was directly proved.


Electrophysiological studies of two types of thalamo-cortical neurones and their responses to stimulation of mesencephalic reticular formation. 1. Thalamo-cortical (T-C) neurones projecting their axons to the motor cortex were recorded intra- or extra-cellularly in the anterior ventral and lateral ventral nuclear complex of the thalamus in lightly nembutalized cats. The T-C neurones were identified as responding antidromically to stimulation of the motor cortex, and were examined in connection with effects of stimulation of the centrum medianumparafascicular complex (CM), pallidum (Pal), cerebellar nuclei (CN) and mesencephalic reticular formation (RF). 2. The T-C neurones were classified into two groups, A and B. The A-group neurones responded neither to stimulation of CM nor to that of Pal. By contrast, the B-group neurones were activated from either CM, Pal or both. The effect of RF stimulation was facilitatory in many of the A-group neurones whereas it was mostly inhibitory in the B-group neurones. CN stimulation activated most of the T-C neurones in both A and B groups. 3. The A-group neurones were categorized as the deep T-C neurones mediating the deep T-C response of the cortex (the early surface-positive-deep-negative component of the augmenting response) and the B-group neurones as the superficial T-C neurones mediating the superficial T-C response of the cortex (the recruiting response and the late surface-negative-deep-positive component of the augmenting response). Desynchronization of electrocorticograms in response to RF stimulation was suggested to result from inhibition of the superficial T-C neurones and facilitation of the deep T-C neurones.


Comparative aspects of membrane properties and innervation of longitudinal and circular muscle layers of rabbit jejunum. Longitudinal muscle of the rabbit jejunum usually generated burst discharges, whereas circular muscle mainly generated slow potential change. Membrane potential was higher, and the space and time constants were larger in circular muscle than in longitudinal muscle. Current-voltage relationship exhibited anomalous rectification by depolarization of membrane in longitudinal muscle cells, and delayed rectification in most circular muscle. Excitatory junction potentials (e.j.p.s) were recorded from both muscles and inhibitory junction potentials (i.j.p.s) were recorded from only circular muscle. The e.j.p.s consisted of muscarinic e.j.p.s and atropineresistant e.j.p.s, but only the latter were recorded from circular muscle. The i.j.p.s were not affected by either or both alpha- and beta-blockers, but were blocked by TTX. From mechanical and electrical responses of both muscle layers induced by field stimulation, it was postulated that four different types of nerve fibres innervate the jejunum muscles: (I) cholinergic excitatory nerves, (II) non-adrenergic and non-cholinergic inhibitory nerves (or purinergic nerves), (III) non-adrenergic and non-cholinergic excitatory nerves and (IV) adrenergic inhibitory nerves. In the longitudinal muscle, (I) was dominant, but (II) was also found. In the circular muscle all four types were found to exist. Effects of adrenergic nerve stimulation on the membrane potential was not detected by stimulation below 10 Hz, although externally applied noradrenaline at 5.9 X 10(-8)m had a relaxing effect.


Tissue specificity of inhibitory action of excess thyroid hormone on creatine transport in the rat. Tissue specificities in inhibitory action of excess triiodothyronine (T3) on creatine uptake from the plasma and the effect of denervation of the muscle on the inhibitory action were studied in rats with the use of radioactive creatine. The uptake of radioactive creatine of all muscles studied significantly diminished after T3 (100 microgram/100 g, s.c.) injection, while that of brain was not affected by T3 treatment. Tissue specificity of the T3 action on creatine uptake was consistent with that of previously known T3 action on oxygen consumption. The responses to inhibitory action of T3 on creatine uptake were not different in different types of the skeletal muscles. Although the uptake of radioactive creatine of denervated muscles was significantly lower than that of controls, inhibitory action of T3 on creatine uptake was similarly observed in denervated muscles as well as in normal ones. The results indicate that T3 has a direct effect on muscle cell per se and the inhibitory action of T3 on creatine uptake by the muscle is closely related to T3 action on the energy-requiring process in cell membrane.


The effects of phenylephrine in various ionic environments on the circular muscle of mid-pregnant rat myometrium. In 12-15-day pregnant rat myometrium, spikes of the longitudinal muscle were discharged spontaneously in burst, while the circular muscle had predominantly a plateau potential. In the longitudinal muscle, phenylephrine (10(-7) g/ml) slightly decreased the duration of the burst discharge and suppressed the contraction by beta-adrenoreceptor stimulation. In the circular muscle, phenylephrine (10(-7) g/ml) prolonged the duration of the plateau potential leading to an increase in tension without changing the amplitude of plateau, membrane potential and membrane conductance by alpha-adrenoreceptor stimulation. The effects of phenylephrine on the circular muscle in various ionic environments were observed. In K-free solution, spike generation ceased but phenylephrine depolarized the membrane, generated the prepotential with spikes and prolonged plateau duration. In low-Ca solution, spontaneous spike generation ceased and electrically evoked spikes showed short plateau duration. Phenylephrine restored the membrane activity and prolonged the plateau duration. Excess Ca showed either prolonged (less than 5mM) or reduced (greater than 8mM) the plateau duration, but phenylephrine consistently prolonged plateau duration. When Cl was replaced with either Br or benzene sulphonate, the former prolonged plateau duration and increased the excitability, whereas the latter reduced plateau duration and suppressed the spontaneous activity. Phenylephrine prolonged plateau duration in both Cl-deficient solutions. When NaCl was replaced by choline-Cl, leaving 15.7 mM Na remaining in NaHCO3 buffer, phenylephrine action completely ceased. The ionic mechanism involved in phenylephrine action is discussed.


Effects of catecholamines on the circular muscle of rat myometria at term during pregnancy. The effects of catecholamines on the circular muscle of myometria in pregnant rats at term (21st and 22nd days) were investigated by recording electrical and mechanical responses. Slow potentials were found to be the dominant activity in the morning on the 21st day of pregnancy, and spike potentials were manifested on the 22nd day. The alpha-excitation of catecholamines in the circular muscle was represented by mechanical potentiation, prolongation of the slow potential and depolarization of the membrane. In contrast, the beta-inhibition was mechanical inhibition, depression of the slow potential and hyperpolarization. Noradrenaline at a concentration of 6 X 10(-6M caused excitatory action in the circular muscle on the 21st day of pregnancy, while the effect became inhibitory on the 22nd day of pregnancy. Results obtained by the use of adrenergic agonists and antagonists led to the conclusion that the reversal of the effect of noradrenaline could be ascribed largely to the enhancement of the beta-action, the mechanism of which was brought about probably through the endogenous change in the steroid hormone secretion at the very end of pregnancy.


Intracellular recordings from the motor cortex during EEG arousal in unanaesthetized brain preparations of the cat. 1. Intracellular recordings were made from 92 neurones in the precruciate cortex of encéphale isolé and midpontine pretrigeminal preparations of the cat. 2. All but only one of these cells showed appreciable changes in the membrane potential during the transition from the cortical slow wave phase to the EEG arousal occurring spontaneously or induced by stimulating the midbrain reticular formation. Thus, 38 cells were depolarized (D-type cells), 48 cells hyperpolarized (H-type cells) and 5 cells showed an early hyperpolarization and a later depolarization (mixed type). 3. The latency of intracellular responses to reticular stimulation was shorter in the D-type cells than the H-type or mixed-type cells, and shorter for each of the D- and H-types in the cells of the superficial layers than those of the deep layers. 4. The D-type cells were distributed widely through laminae I to V, but the majority was sampled in lamina II. The H-type cells were located in laminae III-VI with the mode at the upper half of lamina III. The mixed-type cells were mostly located in laminge V and VI. 5. Antidromically identified slow pyramidal tract (PT) cells n=9) all belonged to the D-type, and fast PT cells either to the H- (n=11) or the mixed type (n=4). 6. These results suggest that the EEG arousal is a state composed of both excitatory and inhibitory responses of cortical cells which are processed from the superficial to the deep layers.


An intracellular analysis of EEG arousal in cat motor cortex. 1. Changes in the resting potential and the effective membrane resistance were measured in 77 cells in cat precruciate cortex during the transition from cortical slow wave phase to EEG arousal. 2. These 77 neurones were classified into the recipient cells of the following five different actions on the EEG arousal: (1) postsynaptic excitation (E cells), (2) postsynaptic inhbition (I cells), (3) disinhibition (DI cells), (4) disfacilitation (DF cells) and (5) disfacilitation followed by excitation (DF-E cells). 3. The location of E cells ranged from laminae I to V, but the majority was found in lamina II. Most I cells were located in the upper half of lamina III, and a few in lamina V. DF, DI and DF-E cells existed deeply from the lower half of lamina III to laminae V-VI. 4. Slow pyramidal tract (PT) cells (n = 6) all belonged to the E cell group, whereas fast PT cells were divided into the DF (n = 10) and DF-E cell groups (n = 4). 5. It is postulated that the EEG arousal is initiated with a direct excitation of laminae I-II cells, followed by excitation and inhibition to the upper lamina III cells and further processed to laminae III-VI cells with indirect excitation, inhibition, disinhibition and disfacilitation. The model of four vertical transmission relays is proposed to depict the casade pattern of information being processed through the cortex during the EEG arousal.


[The effects of cue stimuli on the reaction times of mentally retarded children: an examination of the temporal factor and the spatial factor (author's transl)]. To investigate the covert behavior performed by retardates during the warning intervals of simple RT task, cue stimuli consisting of a combination of the mode of the temporal presentation (regular vs. irregular) and the mode of spatial presentation (regular vs. irregular), were introduced in the warning interval. Retarded and normal children performed under these conditions. For retardates the spatial regularity was more effective than the temporal regularity. For normals there was little RT difference among the four experimental conditions. Retardates had minimized RT under the condition in which the cue stimuli were presented regularly in the spatial order. These results suggested the difference in the covert behavior performed by retardates and normals.


[A study of psychological stress: observations of serial performance under the stress induced experimentally by different kind of procedures (author's transl)]. This paper aims to investigate the common changes observed in serial performance irrespective of any stressors experimentally prepared, examining the relations between common changes under stress and personal types of performance. Sixty-six students served as subjects. Measurements of serial reaction time, variance in speed of performance, blockings, corrections, errors, omissions and repetitions were made on simple color naming (experimentally non-stress), competitive color naming (stressor, incongruent stimuli) and high-speed color naming (stressor, controlled high-speed). The results showed that stressors of different kinds induced common changes and the indices of stress implied magnified features of personal types of performance. These findings were discussed in terms of Selye's theory of stress.


[Experimental studies of the esophageal blood flow on the pathogenesis of achalasia (author's transl)]. In order to elucidate the pathogenesis of achalasia, adult mongrel dogs were used for experimental research on the blood flow to the esophagus following bilateral cervical vagotomy. The control group consisted of forty dogs which were subjected to acute experiment. Thirty dogs were sacrificed for induced-achalasia-like animal. However only seven of them were eligible for this study. The measurement of the blood flow was taken from two sites of the esophagus by using the thermoelectrical method, the upper one was located at 2 cm distal to V. hemiazygos, the lower one 2 cm proximal to the esophageal hiatus of the diaphragm. The following conclusions were obtained. 1. On adrenaline loading, an increasing blood flow to the esophagus was observed in the control group. 2. A decreasing blood flow was demonstrated in the achalasia-like group. 3. The disagreement of the above two measurements could be abolished on administration of an alpha blocking agent; phentolamine. Accordingly, a decreasing blood flow to the esophagus on adrenaline loading in achalasia-like group in contrast to the control one greatly suggested that the abnormality of the blood flow to the esophagus might predispose to the pathogenesis of the achalasia.


[Electromyographical study on the residual stomach following proximal gastrectomy (author's transl)]. The role of the antral gastric vagi and the pyloric sphincter on the residual stomach following proximal gastrectomy were studied electromyographically, using adult mongrel dogs. At the first stage of surgery, proximal gastrectomy was performed preserving the bilateral antral gastric vagi followed by esophagogastrostomy by end-to-side anastomosis. The residual stomach was equipped with four bipolar silver needle electrodes and two waterproof strain gauges on the wall of the stomach. At the second and third stage of surgery, the same dog subsequently underwent trancal vagotomy and pyloromyotomy at 4 weeks intervals. Following proximal vagotomy, the interval of the BER in fasting was prolonged. Dysrhythmia was observed quite frequently, and the amplitude and rhythmicity of contractile activities of the residual stomach became lowered and distorted, however, after feeding the interval of the EBR was shortened and dysrhythmia was altered to a regular rhythmic pattern. Frequent episodes of vomiting were observed following over feeding. Subsequent trancal vagotomy showed increased incidence of dysrhythmia in fasting, and gave no favourable effects on the vomiting episodes or the amount of feeding. After pyloromyotomy, the amount of feeding could be increased by about 50% from the original optimal amount.


[An electromyographic study of the stomach after selective proximal vagotomy in dogs (author's transl)]. To clarify the gastric motor function after selective proximal vagotomy (SPV) by electromygoraphy in dogs, I designed the following experimental groups; Group I is the control, untreated dogs; Group II is SPV operated dogs; Group III is selective antral vagotomy (SAV) operated dogs. The gastric electromyogram was taken from fasted food stimulated, and insulin stimulated dogs in each groups, and the recording was begun two weeks after the operation. The results are summarized as follows. 1) There were no significant differences in discharge intervals before and after food and insulin stimulation in all groups. 2) The propagation velocity was delayed markedly in SPV- and SAV-operated dogs compared to the untreated dogs before stimulation. 3) It seemed to be that the delay of propagation velocity at fasting, was more prominent in SAV than in SPV. Therefore, it is suggested that antral branch might play an important role on the gastric motor function.


[Effect of synthetic motilin on gastric motility (author's transl)]. The effects of the synthetic motilin on the gastric motility were investigated in the dogs with innervated antral pouches in fasting state. The results were as follows: 1) The synthetic motilin stimulated markedly the gastric motor activity in both the contraction pressure and the frequency of the peristalsis. 2) Tetragastrin produced more regular and higher frequent contractions compared with synthetic motilin, but acted to weaker the contraction pressure. 3) In simultaneous administration of the synthetic motilin and the tetragastrin, the synthetic motilin acted more strongly in the contraction pressure, on the other hand tetragastrin in the frequency of the peristalsis. 4) The peristaltic contractions induced by synthetic motilin were completely abolished by the administration of the atropine sulfate. 5) Under medical vagotomy, synthetic motilin was not able to produce any peristatlic contractions, but tetragastrin stimulated strongly the gastric motility.


[The initiation and propagation of canine pelviureteral contraction studied through visual observation and simultaneous electromyographic recording (author's transl)]. The initiation and the propagation of the ureteral peristalsis were studied through the visual observation and the simultaneous recording of action potentials at both renal pelvis and ureter. The results were summarized as follows: 1) The contraction waves were seen to arise at the proximal end of the renal pelvis. Each wave moved from its origin across the adjacent part of the renal pelvis toward the pelviureteric junction forming a crescentric wave front centering the pelviureteric junction. But some waves failed to propagate not only at the pelviureteric junction but also within the renal pelvis. 2) By electromyographic study, pacemaker potentials were recorded clearly at the proximal end of the pelvis and the interval of the discharge was constant throughout the recording period. Some of the electrical waves failed to conduct within the renal pelvis as well as at the pelviureteric junction.


Glomerular permeability: transfer of native ferritin in glomeruli with decreased anionic sites. Polycations induce loss of fixed anionic sites in the glomerular capillary wall and epithelial changes similar to those reported in proteinuric conditions. To investigate whether such alterations are accompanied by an increase in glomerular permeability, the distribution of anionic ferritin was studied in kidneys perfused with a polycation (protamine sulfate). Cortical biopsies were examined by light and electron microscopy. Glomerular anionic sites were studied by the colloidal iron reaction. In kidneys perfused with protamine, whether or not pretreated with heparin, there was a marked decrease in glomerular polyanion, a flattening and loss of foot processes, and a significant increase in number of ferritin molecules beyond the inner aspect of the glomerular basement membrane, relative to controls. When protamine-treated kidneys were reperfused with heparin, there was restoration of glomerular polyanion, nearly complete reversion of epithelial changes, formation of protamine-heparin complexes in the capillary wall, and a ferritin distribution comparable to that of controls. These results provide additional evidence evidence of the restrictive role of the glomerular polyanion with respect to the filtration of anionic proteins.


Topography and numerical densities of intramembrane particles in chemical carcinogen-induced urinary bladder carcinomas in Fischer rats. Integral membrane proteins are visualized as intramembrane particles (IMP) at the cleaved surfaces of freeze-fractured plasma membranes. Topographical distributions of the IMP of the urinary bladder epithelial cells membranes in normal Fischer rat bladder and noninvasive and invasive N-(4-(5-nitro-2-furyl)-2-thiazolyl)formamide (FANFT)-induced bladder tumors are shown to be significantly different. Using several statistical methods that test IMP topography vis-a-vis the Poisson (random) hypothesis, it is demonstrated that IMP are mathematically randomly distributed in the large majority of plasma membranes of cells in normal rat bladder epithelium and in invasive N-(4-(5-nitro-2-furyl)-2-thiazolyl)formamide tumors. In noninvasive rat bladder carcinomas, IMP are in a lattice-like arrangement in half of the tumor cells and randomly distributed in the remainder. IMP numerical densities are also altered in the course of neoplastic transformation. IMP are equally increased above control values in both noninvasive and invasive N-(4-(5-nitro-2-furyl)-2-thiazolyl)formamide tumors. Although transformation into noninvasive tumors is associated with increased numbers of IMP, there is no evidence that this parameter is specifically related to tumor biologic behavior in this model system.


Central nervous system demyelination and remyelination in the mouse: an ultrastructural study of cuprizone toxicity. Male weanling mice (Biobreeding Laboratories) exposed to the drug Cuprizone (biscyclohexanone, oxaldihydrazone) in the diet for periods of 6 weeks and longer, consistently showed almost complete demyelination of the superior cerebellar peduncle. The demyelination was primary and followed degeneration of oligodendrocytes and their processes, whereas axons remained intact. After formation of myelinic vacuoles and removal of myelin by macrophages and astrocytes, the axons became invested with astroglial processes. As part of the glial response to demyelination, numerous reactive or immature cells appeared, some of which were identified as being either astrocytic or oligodendrocytic in nature. Some mature oligodendrocytes survived. When allowed to recover on a normal diet, remyelination began within a week, and progressed until all axons were myelinated. The mechanism of remyelination appeared similar to the spiral wrapping mechanism seen in normal development. The myelinating cell in all cases was the mature oligodendrocyte. Sources for these oligodendrocytes include residual surviving oligodendrocytes, differentiation of immature forms, and possibly the perineuronal satellite cell. The sheaths eventually reached a thickness approximately half that of normal development, with a disturbed relationship between myelin thickness and axon diameter. A visual impression of shortened internodal length was obtained. It is concluded that the Cuprizone model is an excellent situation in which to study the cellular mechanisms of demyelination and remyelination.


The epithelial cell component of the thymuses of aged female BN/Bi rats: a light microscopic, electron microscopic, and autoradiographic study. Thymuses of virgin female BN/Bi rats of various ages were studied by light microscopy, electron microscopy, and autoradiography. The thymuses appeared to undergo a normal involution during the first 2 years of life. In rats 2 to 4 years of age, there was an apparent proliferation of epithelial cords and tubules suggestive of a true hyperplasia. The appearance of these epithelial cords and tubules in the otherwise atrophied thymuses of old animals (more than 30 months of age) is described. The predominant epithelial cell type, containing dark apical granules, showed morphologic evidence of secretion. 3H-leucine labeling confirmed active protein synthesis and secretion by these cells. Lymphocytes and macrophages were identified within the lumina and between the epithelial cells of the epithelial cords and tubules suggesting that they were able to migrate into and probably out of these structures.


Pathologic changes in the lungs of oxygen-adapted rats: a morphometric analysis. Animals exposed to 85 per cent O2 for 5 or more days acquire the ability to survive for prolonged periods in 100 per cent O2. The basis of this acquired "tolerance" is poorly understood, but it has been proposed to be related to biochemical changes occurring in the lung cells. In order to quantify the structural changes that occur in the lungs of oxygen-adapted rats, rats were exposed to 85 per cent O2 for 7 days and then studied using morphometric techniques. The oxygen-adapted rats had a normal number of alveolar type I epithelial cells and a moderate increase in the number of alveolar type II cells. The alveolar type I epithelium was intact over the entire alveolar surface and appeared to have a normal ultrastructure, whereas alveolar type II cells demonstrated occasional changes in mitochondrial structure. In the interstitial compartment, there was a large increase in the number of interstitial cells and a significant increase in the noncellular components of the interstitium. The major area of pulmonary damage occurred in the vascular compartment, where entire segments of the capillary bed were lost and the total number of endothelial cells decreased by 45 per cent. A significant change in pulmonary vascular hemodynamics was suggested by a 49 per cent decrease in total capillary lumen volume and a decrease in the hematocrit of blood in the pulmonary capillary lumen to 57 per cent of the value found in aortic blood.


Women alcoholics' responses to Scale 4 of the MMPI. Responses to three items of Scale 4 of the MMPI accounted for the significant difference between the mean scores of women alcoholics and women psychiatric outpatients. Factor analysis of alcoholics' responses yielded six interpretable factors.


Sex roles and drinking among adolescent girls. Attitudes toward traditional feminine ideals did not distinguish adolescent girls who drink from those who do not drink. However, among White, Black and Spanish-American girls who drink, rejection of traditional femininity was associated with drinking more, more symptomatically, and with more problem consequences.


Alcohol and rape in Winnipeg, 1966-1975. Either victim or rapist or both were drinking prior to 72% of the rapes occurring in Winnipeg from 1966 through 1975, and the presence of alcohol increased the likelihood that the victim would be injured prior to sexual intercourse.


Autonomic nervous system concomitants of short-term abstinence in alcoholics; Pupillometric studies. II. During rest, stress and homeostatic recovery, drinking and nondrinking alcoholics showed impaired pupillary contraction, but the pupillary dilation in drinking alcoholics was slower and more attenuated than that in nondrinking alcoholics and nonalcoholics.


Slowing of short-term memory scanning in alcoholics. Hospitalized alcoholics taking disulfiram were found to process information in short-term memory at a slower rate than hospitalized controls, although short-term memory capacity was similar in the two groups.


The influence of ethanol on learned and reflexive heart rate responses of rats during classical aversive conditioning. An unconditioned response was produced in rats by electric shock and resulted in a biphasic deceleration-acceleration of heart rate after 2.4 g of ethanol per kg. A monophasic acceleration occurred with saline and 0.8 g of ethanol per kg.


Variability of the blood:breath alcohol ratio in vivo. The blood:breath alcohol ratio, commonly used to translate the result of breath alcohol analysis into the co-existing blood alcohol concentration, varies from person to person and within one person over time.


A comparison of the MacAndrew Alcoholism Scale and the Michigan Alcoholism Screening Test in a sample of problem drinkers. In a sample of problem drinkers, the Michigan Alcoholism Screening Test performed best with subjects who identified themselves as alcoholics, whereas the MacAndrew Alcoholism Scale worked best with patients in the more advanced stages of alcoholism.


Differentiation of alcoholics by family history. Alcoholics having a family history of alcoholism tended to drink at an earlier age and to have more social and personal problems than do alcoholics not having a family history of alcoholism.


Psychometric assessment of alcoholism in convicted felons. Felons' scores on the Short Michigan Alcoholism Screening Test tended to be positively correlated with their scores on clinical scales of the Minnesota Multiphasic Personaltiy Inventory.


Pre- and posttraining MMPI scores of women alcoholism counselors. The scores of women alcoholism counselors on the Minnesota Multiphasic Personality Inventory before and after completion of an intensive training program showed little change in basic personality configuration.


Cannabis in the treatment of alcoholism. Cannabis, alone or in conjunction with disulfiram, was not particularly effective in inducing alcoholics to enter or remain in treatment.


Alcohol problems in several midwestern homosexual communities. According to their scores on the Michigan Alcoholism Screening Test, close to one-third of the homosexual men surveyed in four urban areas of Kansas were alcoholics.


Expectancy of alcoholism in a midwestern population. The morbidity risk of alcoholism among men in a Midwestern population varied between 5.4 and 7.2%, depending on the criteria used. Among women the morbidity risk was about 0.4%.


Prediction of cerebral dysfunction in alcoholics; a study of health insurance records. During a 5-year period, alcoholics having few periods of mental illness interfering with their capacity to work were socially more stable but had more signs of cerebral dysfunction than did alcoholics having more periods of such illness.


Ethanol metabolism and memory impairment in American Indian and white women social drinkers. American Indian women metabolized a moderate dose of ethanol significantly more rapidly than did White women of similar age, education, weight and drinking history; however, the two groups demonstrated a similar memory decrement due to ethanol.


Evidence of active transport (filtration?) of plasma proteins across the capillary walls in muscle and subcutis. Under slight lymphatic stasis (tilting the body 15 degrees) we measured the arrival of locally injected I-albumin to the plasma pool. From 30 min. to 90 min. after the injection the return rate was zero i.e. local back transport in the two tissues studied viz.muscle and subcutaneous fat is very small. Compared to a suggested steady state total 131 I-albumin clearance of 1.7%/hour in the horizontal body position we conclude that maximally one percent of the interstitial albumin can have a local transendothetial escape i.e. can be handled by passive forces as is diffusion and pinocytosis. As passive flux is proportional to the concentration and the interstitial albumin comcentration is about half the plasma concentration then also diffusion and or pinocytosis from the plasma of albumin is negligble in the resting normal man. We suggest filtration through big leaks as the main mechanism for transendothelial protein transport.


Intra- and extravascular distribution of albumin and immunoglobulin in man. The plasma proteins are constantly shuttling between intravascular and extravascular mass of a specific plasma protein is determined by its individual rate of synthesis and the mean total time it spends in plasma. The ratio of intravascular to total mass (distribution ratio) is determined by the relative rate, at which it passes from plasma to interstitial spaces (transcapillary escape rate: TER) and the relative return rate via lymph. TER in a specific organ depends on the local leakiness of the microvasculature. The overall value in normal man varies with the molecular weight of the protein being about 5%/h of the intravascular albumin mass, 3%/h for IgG and less than 1%/h for IgM. The higher the TER, the lower is the intravascular fraction. Hypertension, diabetes mellitus, burns, myxedema and certain types of liver cirrhosis will increase TER. In hypertension and diabetes this may be compensated for by an increased lymphatic return rate. Hypoproteinemia due to malnutrition or urinary or gastrointestinal loss is accompanied by a shift from the extravascular to the intravascular space.


Protein concentration in lymph.

Protein concentration in lymph. A brief review is given on the problem of protein concentration in lymph versus protein concentration in interstitial fluid. The possibility of a concentrating ability of the lymphatics is discussed in the light of recent investigations. It is concluded that the final answer to the problem is not known, but that substantial evidence indicate that the protein concentration in lymph and in the interstitial fluid from which the lymph originate is similar.


Immune proteins, enzymes and electrolytes in human peripheral lymph. Values of various biochemical constituents of leg lymph in 27 normal men have been presented. Concentration of immunoglobulins, complement proteins, acute phase reactants, enzymes, electrolytes and other small molecular weight substances were measured.


C1q-binding substances in peripheral lymph in bronchial carcinoma. Peripheral leg lymph has been studied for the presence of C1q-binding substances by the I-C1q binding radioassay in six male patients with untreated bronchial carcinoma. In serum, this assay is highly specific for antigen-antibody complexes (immune complexes). Three of the patients had immune complexes in serum, and they all also had C1q-binding substances in peripheral lymph. The C1q-binding activity was quite similar in serum and peripheral lymph. In the other three patients, immune complexes were not found in serum, but in ome of them, moderate amounts of C1q-binding substances were found in peripheral lymph. The results suggest that immune complexes may be found in peripheral lymph in cancer patients in about the same amounts as in serum. However, formal proof is lacking that the C1q-binding substances of peripheral lymph are real immune complexes.


Immune proteins and other biochemical constituents of peripheral lymph in patients with malignancy and postirradiation lymphedema. Concentration of immunoglobulins and complement proteins were studied in a group of 33 patients with localized tumors and lymphoproliferative disorders. Generally, low levels have been found, in many cases below the lowest limit of the control group. The reductions in concentration were more pronounced in patients with lympho-proliferative disorders than with solid tumors. The most reduced were IgM, C1g and total complement hemolytic activity. In a group of 8 patients with lymphedema of lower extremity complicating therapy for uterine cancer an increase of IgM and IgA and decrease in hemolytic activity were found. This indicates to the existence of a chronic inflammatory process, typical for tissues deprived lymphatic outflow.


Distribution of methotrexate between plasma and peripheral lymph in man. The distribution of methotrexate (MTX) to interstitial fluid has been studied by determination of MTX in peripheral lymph from the leg and in plasma after parenteral administration to 6 patients. Peak concentrations of MTX in lymph appear 0.5 to 3.25 h after peak concentrations in plasma. Maximal concentrations in lymph are 16 to 48% lower than in plasma. MTX concentration ratios lymph/plasma were higher than 1.0 (1.0-2.8) in 4 patients, and lower than 1.0 (0.2-0.8) in 2 patients. 12 to 34% of MTX was protein bound in lymph, but the variation in the ratio of bound to free MTX per g lymph protein was only 0.13 to 0.18. The patients with a lymph/plasma MTX ratio above 1.0 will have high and favourable MTX concentrations for distribution to tumours in peripheral tissue, while in the patients with a low ratio conditions for distribution are less favourable. The results indicate that pharmacokinetics of MTX are in accordance with a two or multicompartment model with varying distribution characteristics. The present observations indicate that distribution of MTX is blood flow limited, but the influence of permeability cannot be excluded.


Interstitial handling of aminoglycoside antibiotics and radiographic contrast media in the kidney. Lymphatics of the mammalian kidney originate in the loose connective tissue around large blood vessels. This paravasal tissue drains the interstitum. The intarenal lymphatic system consists of interlobular, arcuate, and interlobar vessels according to the architecture of the arterial system. The interlobar vessels drain into the hilar lymph vessels. Capsular lymphatics are connected with the interlobular lymphatics inconsistantly. The renal medulla is drained by the venous vasa recta exclusively--there are no lymphaties in the medulla. Lymphatic fluid is mainly formed along the small renal veins as vascular transudate. After i.v. bolus injection concentrations of aminoglycosidic antibiotics in renal lymph reflect plasma values closely. Radiographic contrast media in renal lymph also showed a close correlation with plasma values with some indication of tubular secretion.


Recirculation of lymphocytes: its role in implementing immune responses in the skin. A number of recent investigations have suggested that the subset of lymphocytes which migrate into nonlymphoid tissue to appear in peripheral lymph may be partly different from the major recirculating pool migrating through lymphoid tissues. We report results on the migrating from the blood of thoracic duct lymphocytes labelled with Cr and three subsets-accredited recirculators, activated lymphocytes and long-lived lymphocytes. The localization of these populations was studied in normal skin, in a contact sensitivity lesion and in a site of non-immune inflammation. All four populations localized in the contact sensitivity lesion in increased numbers compared to normal skin but long-lived lymphocytes appeared to discriminate between cell-mediated immunity and non-immune inflammation; activated lymphocytes migrated most efficiently into the non-immune inflammatory site (Table 4).


Cells in peripheral leg lymph of normal men. The cells of human peripheral lymph collected from leg lymphatic of healthy volunteers have been studied by light- and electron microscopy. More than 80% of the cells were lymphocytes. The rest of the cells were neutrophils, monocytes, phagocytes, intermediate forms between lymphocytes and monocytes, erythrocytes and large cells. Ultrastructurally these large cells had many features in common with the Langerhans cells of normal epidermis and may represent this cell type or a closely related one.


Lymphocyte migration through the walls of the post-capillary venules. The results of morphological analyses of the direction of the lymphocyte traffic through the walls of the HE-venules are conflicting. The aim of this paper is to provide a short analytical review of the evidence available for the bi-directional hypothesis and for the uni-directional hypothesis.


Influence of corticosteroids on lymphocyte recirculation. The effect of corticosteroids on cell kinetics and cell size distribution in the circulating lymphocyte population of the steroid sensitive rat and the steroid resistant guinea pig were studied. A single high steroid dose (prednisolone) induced a rapid depression of the lymphocyte level both in normal and thymectomized animals of both species and a restitution within one day. The returning cell population showed the the same size distribution and label index profile as before involution. The main effect of a single steroid dose seems to be a "trapping" of lymphocytes with redistribution from the circulation to some tissues. The difference between the two species seems to be quantitative with a more pronounced trapping mechanism in the sensitive rat but a certain degree of lymphocytolysis cannot be excluded in this species. The steroid action seems to be on both T- and B-lymphocytes and the restitution of cell levels after acute involution is independent of an intact thymic function. The same course of events was observed in the normal rat after stress, but not in the thymectomized rat.


Whole body localization of intravenously injected lymphoblasts in normal rats. Total body distribution of IUDR labeled thoracic duct, mesenteric and peripheral lymph node blasts was investigated, after i.v. injection into normal syngeneic rats. Donors of immunoblasts were stimulated with SRBC 1 week before transfer of cells. Lymphoblasts, irrespective of the source of origin, accumulated preferentially in small intestine, lungs, skin and muscles. There was an evident difference in the whole body distribution pattern of injected thoracic duct and lymph node blasts, what points to the different behaviour of normally circulating immunoblasts. Only minor differences in distribution kinetics and sites of accumulation were found between mesenteric and peripheral blast cells. We put forward a hypothesis that immunoblasts behave like effector cells and their preferential localization in small gut, lungs, and skin may be mediated by antigens "physiologically" present on the surgace of tissue with direct contact with the external environment.


Developmental changes in rat adrenocortical cell membrane potential. Resting membrane potentials of zona fasciculata-reticularis cells of the rat adrenal gland varied with age. The mean membrane potentials of newborn rat adrenal cells was -56.4 +/- 0.7 mV in the first week of life. The mean potential increased slightly to -61.9 +/- 0.8 mV in the second week and then decreased with age to a mean of -38.5 +/- 0.8 mV in 25--50 week old rats and of -25.9 +/- 1.9 mV in 100 week old rats. The changes in membrane potential may correlate with the indices of adrenocortical growth and activity.


Comparison of RNA synthesis by liver nuclei from rats of various ages. RNA synthesis was studied in nuclei isolated from male Fischer F344 rats of various ages. Both the initial rate and the extent of RNA synthesis were determined in two distinct media that result in the preferential synthesis of either mRNA or rRNA by hepatocytes. Synthesis of mRNA and rRNA, as determined by [3H]-UMP incorporation into acid-insoluble material, was shown to increase 1.6- to 3-fold from 3- to 6-months. The increase in RNA synthesis during maturation was followed by a 1.6 to 2.7-fold decrease from 6- to 31-months of age depending upon the assay medium and time of incubation. The age-related changes in RNA synthesis by rat liver nuclei were shown not to be due to changes in RNase activity, UTP uptake, or UTP degradation. RNA synthesized by liver nuclei from rats of various ages was characterized by SDS--polyacrylamide gel electrophoresis. Slight age-related differences in the size distribution of RNA isolated from liver nuclei were observed when nuclei from rats of various ages were incubated with [3H]-UTP in either assay medium.


Hypodiploidy and serum immunoglobulin concentrations in the elderly. Chromosome analyses and Ig level determinations were carried out on seventeen aged men and women, 83--100 years of age. In men, significant correlations were found between hypodiploidy and IgA (gamma = 0.95) and between monosomy C and IgG (gamma = 0.79) while in women, monosomy G and IgG were significantly correlated (gamma = 0.73). The emergence of significant correlations between chromosome loss and Ig levels in this study provides support for  a relationship between age-associated chromosomal changes in T cells and the immunologic response of B cells.


Nucleolar changes in senescing WI-38 cells. Changes in the area, dry mass and morphology of nucleoli were studied during in vitro aging of WI-38 cells. Interferometric methods were used for nucleolar dry mass determinations. The results show that there is (1) an increase in the fraction of cells with one large nucleolus per nucleus, 17% at population doubling 27.3 vs. 93% at population doubling 41.2, (2) an increase in mean nucleolar dry mass (583% at the last doubling), and (3) an increase in mean nucleolar area (236% at the last doubling) with in vitro senescence of WI-38 fibroblast cells. A strong correlation (r = 0.92) between nucleolar dry mass and nucleolar area was demonstrated.


Fatty acid pattern and cholesterol in skeletal muscle of men aged 22 to 73. In order to examine the relationship between fatty acid distribution of skeletal muscle membranes and age, a needle biopsy was performed on the vastus lateralis muscle of 20 healthy, non-obese males, ranging in age from 22 to 73 years. The muscle sample was homogenized, centrifuged at 100,000 x g, and the resulting pellet was saponified and acidified. The fatty acids and cholesterol were removed by a single hexane extraction and analyzed by gas--liquid chromatography with flame ionization detection. All subjects regardless of age had no consistent differences in the fatty acid profiles and cholesterol composition in the tissue. Correlation coefficients indicated no significant relationship between the age of the individual and any of the analyzed lipids. The results of this study indicated that aging may not be reflected by gross changes in the composition of structural lipids in the cell.


Age related alterations in the chromosomal proteins from human diploid fibroblasts. Histone and non-histone chromosomal proteins from human diploid fibroblasts of different in vitro ages were extracted and subjected to SDS--polycrylamide gel electrophoresis. The proteins were taken from cells maintained in three distinct culture states: preconfluent (log phase of growth), confluent (stationary phase of growth), and arrested (presumptive G0 phase). Age associated alterations in the incorporation of radioactive amino acids were detected in the fractionated proteins in every culture state but were less pronounced during the arrested state. Age related difference detected under growth conditions may reflect variations in the proliferative nature of the populations. Differences seen during the arrested state may be indicative of basic changes in the chromosomal protein complement of different age populations.


The distribution and lipid composition of ultracentrifugally separated lipoproteins of young and old rat plasma. The lipoproteins of young and old Wistar rats differ markedly in distribution and chemical composition. The major differences are: (1) the presence of high levels of free and esterified cholesterol, triglycerides and free fatty acids in the lipoproteins of old rat plasma when lipids are analyzed/100 ml of plasma. However, the ratio of total cholesterol to protein mass indicates the presence of comparable cholesterol pools in all lipoprotein fractions of young and old rats excepting the d 1.063--1.21 fraction where a higher cholesterol pool in old rats is indicated. (2) The amount of sphingomyelin increases in lipoprotein fractions of old rat plasma thereby actually decreasing the lecithin/sphingomyelin ratio in these plasma fractions. (2) Unsaturated fatty acids predominate in young rat plasma lipoproteins, and saturated fatty acids predominate in old rat lipoprotein fractions. The ratio of polyunsaturated (linoleic, linolenic, arachidonic) to saturated (palmitic, stearic) fatty acids in young rat sera was 0.89 and in old rat sera, 0.55.


[Histological classification of early gastric cancer in 300 cases - clinical significance (author's transl)]. Early gastric cancers of 300 patients were evaluated using the Lauren approach of histological classification, that is to say distinguishing between a diffuse and an intestinal type of cancer. It turned out, that the role of gastritis in the pathogenesis of early gastric cancer is rather ill defined. A high percentage of early cancers of the diffuse type were found in gastric mucosa showing no inflammatory changes whatsoever. From the point of view of pathogenesis both types of cancer have to be considered as separate nosological entities. This difference is most obvious during the early stages of development. Therapeutical consequences will certainly have to be drawn in the future from this subdivision for patients at risque. Early gastric cancer presents in a high percentage of cases at first as an ulcerative lesion; this stresses the importance of careful gastroscopic and bioptic examination of patients with gastric ulcera, and of frequent examinations of these patients.


[End-to-side mesenteric caval in children - significance of blood flow physics in defining the surgical procedure preoperatively (author's transl)]. Elevated blood pressure of the portal circulation in children may be lowered to defined levels by end-to-side shunting of the mesenteric and the portal vein. The question is, whether an optimal geometry of the ellipsoid anastomosis can be calculated preoperatively. A simplified model of the shunt system is presented using electric and hydraulic analogs of the real blood flow physics. It is not taken into account in this model, that there are two capillary beds connected in series in the portal circulation, which both exhibit high blood flow resistance. Shunt resistance as being calculated on the basis of this model in 6 children, and real shunt resistance as being measured in these patients intraoperatively actually turned out to be in the same order of magnitude inspite of the handicaps of the model. Thus to our opinion the calculations presented are suited to determine preoperatively the optimal geometry of an ellipsoid shunt anastomosis intended to lower blood pressure in the portal circulation to levels as desired.


[Umbilical collateral circulation in liver cirrhosis - Cruveilhier-v. Baumgarten syndrome (author's transl)]. Embryonal development and anatomy of the liver are shortly discussed; they do explain collateral circulation in liver cirrhosis. A case report is given of a patient with umbilical collateral circulation (Cruveilhier-v. Baumgarten syndrome), exhibiting impressive clinical and radiological findings. Such an umbilical collateral circulation will develop in up to 21% of all patients with an intrahepatic block. This is only one variant - not prone to complications by the way - of a multitude of different portosystemic shunts in liver cirrhosis. Therefore it should not be talked about as an independent syndrome.


[Liver cirrhosis in Israel (author's transl)]. The incidence of death caused by cirrhosis of the liver has increased in Israel during the last 20 years as it has in other parts of the world; still the incidence is much lower than in most countries. Increasing alcoholism and higher rates of hepatitis probably play a role, however in many cases the cause of cirrhosis remains in the dark.


[Minerals in normal and cirrhotic liver. The pathology of mineral dependent athrocytic liver cirrhosis]. Concentrations of iron, copper and zinc were measured in postmortem specimens of liver, muscle and brain tissue by atomic absorption spectrophotometry. Concentrations varied markedly in normal liver specimens from person to person, but not in other organ specimens. Copper concentrations in specimens from cirrhotic livers were normal in most cases, however at the upper limit of normal in about 20% of the cases evaluated. Concentrations of zinc and iron were lower than normal in cirrhotic livers. Mineral concentrations were higher by a factor of 10-20 in liver specimens of patients with hemochromatosis or M. Wilson than in normals. Iron overloading as a consequence of therapy (secondary hemochromatosis) and liver changes due to longtime artificially elevated plasma copper levels may imitate the adult form of the "classic" mineral storage diseases mentioned. Thus "athrocytotic" liver cirrhosis, being caused or accompanied by metal excess has to be considered as a polyetiological syndrome.


[Absorption and oxidation rate of arginine and malate (author's transl)]. Six normal volunteers received L-Arginin and DL-Malat p.o. in order to test absorption and utilisation of these compounds. Both compounds are almost completely reabsorbed from the intestine and then metabolized. Only about 2% of the arginine applied are recovered in the urine. 15% of arginine and 45% of malate applied are metabolized within 8 hours. If absorption is unimpaired oral therapy of hyperammoniemia would require application of the malate-arginine solution for every 3 hours, if constant plasma levels are to be achieved.


[Radiolucent pigment gallstones (author's transl)]. Pigment gallstones may be subdivided into three different types: radiolucent and radioopaque stones in the gallbladder and radiolucent stones in the common bile duct. 35 of our patients had radiolucent pigment stones in the gallbladder; 21 of these were followed for years by repeated X-ray examination. There is only little enlargement of these stones as time passes by, however the number of these stones increases continuously. Chemical analysis could be done on such stones in 24 cases. The stones were composed of granular calcium bilirubinate and of asphalt-like products derived from abnormal bilirubin degradation. 5 patients had pigment stones in the common bile duct. These stones contained little cholesterol and exhibited a spongy microstructure characterized by small tubules with a diameter of 1 micrometer. They contained more lipids and bilirubin than the stones collected from the gallbladder and on extraction with organic solvents no asphalt-like residues could be obtained.


[Gallstone composition and dissolution by chenodesoxycholic acid (author's transl)]. 208 gallstones were collected in sequence and subjected to chemical analysis. Only 10.6% of these stones turned out to be purely composed by cholesterol and only these can be considered to be suited for therapy with chenodesoxycholic acid (CDC). Gallstones composed exclusively by cholesterol cannot be identified in vivo; therapy with CDS has to be followed closely by multiple X-ray and laboratory examinations; in addition there are many relapses after therapy with CDC. For these reasons we still tend to prefer surgery as the therapy of choice in gallstone disease.


[Retroperitoneal perforation of the gallbladder (author's transl)]. Perforation of the gallbladder into the retroperitoneum is a very rare event. A case report is given of a 71 year old patient suffering from acute cholecystitis. A perforation occurred and a retroperitoneal abscess developed. Cholecystectomy, appendectomy and retroperitoneal drainage were performed, and the patient recovered. A review from the literature is given covering 6 other cases.


[Effect of mixture of nitric and chlorine oxides on lymphocyte acid phosphatase activity in rats]. In rats chronically exposed to the mixture of nitric (1.22 mg/m3) and chlorine (1.02 mg/m3) oxides acid phosphatase activity (AcP) in peripheral blood lymphocytes as well as its intracellular distribution, were studied using Barka and Anderson's cytochemical method. Depressive effects of these compounds upon lymphocytic system were found in form of lymphocytopenia and a decrease in AcP--negative lymphocytes percentage. Evaluation of intracellular AcP distribution indicated that the mixture of nitric and chlorine oxides intensified enzyme diffusion from lysosomal granules into cytoplasm. The authors believe that lymphocytopenia results from the reduction in B lymphocytes number. At the same time they consider the contribution of these changes to immune reactions of the organism.


[Effect of chronic inhalation of carbon disulfide intoxication on the content of various lipid metabolism indices in rat serum, aorta and cardiac muscle. I. Total fats, triglycerides, free fatty acids in serum, free and esterified cholesterol in serum, aorta and cardiac muscle]. Fatty compounds were examined in blood serum, aorta and cardiac muscle of rats exposed to carbon disulphide in low (0.44 mg/l) and high (0.8 mg/l) concentration for 3 and 6 months in the toxicological chamber. The content of total lipids, triglycerides and free fatty acids in serum was determined using methods adopted in laboratory diagnostics. Separation of neutral fats in serum and tissue was done using thin--layer chromatography and free and esterified cholesterol was quantitatively determined by colorimetric methods. Statistical analysis of the results was based on the Student's test. In the rats intoxicated with CS2 increased content of total fats, triglycerides, free fatty acids in serum and cholesterol in cardiac muscle was found; these changes are not statistically significant. Statistically significant increase of free and esterified cholesterol was found in serum and aorta of the rats intoxicated with CS2. These changes were found mostly in rats intoxicated for 3 and 6 months with low concentrations of CS2.


[Effect of carbon disulfide on hemostasis in rabbits. II. Platelet adhesiveness]. Rabbits were exposed to carbon disulphide vapour in toxocological chamber. Increased platelet adhesiveness was found in exposed animals, dependent on CS2 concentration in the chamber and duration of intoxication. The authors suggest that the increased platelet adhesiveness may result from lipid metabolism disturbances.


[Early diagnosis of disseminated intravascular coagulation in the clinic of acute intoxications]. An attempt to early diagnose disseminated intravascular coagulation (DIC) in persons acutely intoxicated with exogenic compounds was undertaken. The investigation involved 56 persons, aged 12--72, in this -- 20 females. In 21 persons intoxicated with carbon monoxide, organic solvents, metallic compounds and Amanita phalloides DIC syndrome was was found, the diagnosis being established -- in 14 persons -- in the subclinic phase. The diagnosis of DIC syndrome was based on results of clinical examination and hemostasis system examinations, enabling to evaluate the effect of free thrombin upon fibrinogen, fibrin and thrombocytes. Clinical observations and results of laboratory test indicate that only early diagnosis of DIC syndrome and thereby an instant inculcation of heparin therapy allow to gain complete remission of hemostatic disturbances in acutely intoxicated persons.


[Occupational diseases in Poland in the years 1971--1977]. The authors present results of analysis of occupational diseases morbidity in Poland in the past 7 years. Data included in individual occupational disease card provided information source. The analysis, apart from general coefficients of occupational diseases prevalence involved: age, sex, duration of exposure to occupational hazard inducing a disease, type of the hazard, and distribution of diseases throughout the country according to voivodeships and branches of national economy. From the material presented, the following conclusions may be drawn: 1. Occupational diseases prevalence in Poland in the years 1971--1977 was slightly decreasing. 2. The greatest coefficients of occupational diseases morbidity resulted from: occupational hearing impairments, infectious and invasing diseases, intoxications, pneumoconioses, vibration disease and diseases of skin and mucous membranes. 3. Most occupational diseases found in Poland in the years 1971--1977 resulted from long-lasting occupational exposure to a hazard. 4. The greatest occupational diseases morbidity in Poland in the period concerned, was that of persons aged 40--59.


[Effect of occupational environment on the occurrence of chronic nonspecific respiratory tract diseases among workers engaged in the production of superphosphates]. The paper was aimed at establishment of the contribution of work conditions to etiology of chronic bronchitis, asthmatic symptoms and lung ventilation disturbances. The investigation involved 354 men producing superphosphate in the Sulphur Processing Plant in Machów near Tarnborzeg and the control group of 276 workers from the same plant but little exposed to industrial dusts. The analysis of mean FEV1 indices with different smoking habits, respiratory tract symptoms and work environment, was based on so called corrected i.e. standardized mean values, with regard to age and increase based on multiple regression equations. In the workers producing superphosphate much more frequent chronic bronchitis (PNO), asthmatic syndrome (ZA) and lung ventilation disturbances were found. Corrected FEV1 arithmetic means in those with PNO and ZA symptoms were significantly lower in those from superphosphate division than in the control group. In addition, in the superphosphate division a significant linear trend of the proportion of lung ventilation disturbances cases, depending on symptoms category, was found. These results reveal harmful effect of air pollution in work environment upon health status of the exposed workers.


[Problems arising from the health status evaluation and certification of diseases developed in countries with different climatic conditions]. Based on the Polish regulations, the authors present problems and difficulties in qualification for business departures into the tropics, as well as diagnostic and certification procedures related to those whose health has been injured during their business trip to the tropics. The authors postulate a greater attention to be paid to this problem and explanation of some doubts resulting from interpretation of operative regulations.


[Biochemical polymorphism in a population exposed to environmental pollutants. Importance of studying the problem]. Genetically conditioned interpersonal differences in reactions to identical doses of medicines make us suppose that some of those exposed to environmental pollutants are at a special risk. This is revealed by detection of some biochemical differences in blood, conditioning a special susceptibility to the effect of some toxic substances. Another method is the so called loading test, aimed at observing the personal reaction to innoxious doses of medicines or toxicants. Recently, biochemical tests have been regarded more and more valid; these tests allow to foresee what medicine metabolism will be like in organism and consequently, how extensive the potential risk of the given person is.


[Health conditions of workers chronically exposed to ethyl gasoline and other petroleum products]. Results of 5-year periodic examinations and SDH, LAP and GGTP activity in blood serum of 207 workers chronically exposed to ethyl gasoline and other petroleum products were analysed. In addition, in the selected groups, the levels of IgA, IgG and IgM immunoglobulins, complement C3 fraction and alpha2 macroglobulins were determined. Results of objective and enzymatic examinations indicate a slight toxic liver lesion. No significant changes in albuminous fractions were found, except a significant reduction in alpha2 macroglobulins.


[Clinical value of ammonia determination in venous blood in chronic cor pulmonale]. The authors have examined 43 workers of the Warszawa works: 20 healthy persons and 23 with chronic pulmocardiac syndrome. An increased ammonia level in venous blood, above 48 gamma %, was found in those with chronic pulmocardiac syndrome with simultaneous circulatory insufficiency. Ammonia level in the blood of those with chronic pulmocardiac syndrome but without circulatory insufficiency was normal. These studies indicate that the increase of ammonia concentration in venous blood in chronic pulmocardiac syndrome results from disturbance in hepatic cell function, intensified during circulatory insufficiency.


In vitro induction of antibody-dependent cytotoxic macrophages by the local anesthetic lidocaine. Normal macrophages were activated to antibody-dependent cytotoxic effector cells by in vitro treatment with the local anesthetic lidocaine. Experiments on the dose-response and time course of the effect oflidocaine showed that incubation of normal macrophages with 10 mM lidocaine for 10 min at 28 C was enough for induction of antibody-dependent cellular cytotoxicity. The activation by lidocaine was accompanied by enhanced phagocytosis of sheep red blood cells (SRBC) sensitized with anti-SRBC antiserum, but not enhanced ingestion of polystyrene latex particles (PLP). These findings suggest that lidocaine, which has various effects on cell membranes, induces some perturbation of macrophage membranes, resulting in activation of Fc receptor functions in antibody-dependent cytotoxicity and phagocytosis.


Lifestyle, health and disease: a comparison between Papua New Guinea and Australia. The proposition that lifestyle is a major determinant of community health is explored by contrasting the features of a rural subsistence community in the highlands of Papua New Guinea and the features of the community in urbanized, industrialized Australia. Reference is made to differences in physical environment, housing, work, social situation, human relationships, patterns of disease, population statistics, diet, growth, obesity, physical fitness, blood lipid concentrations, blood pressure, salt intake and the occurrence of hypertension, diabetes, cardiovascular disease and signs of degenerative changes in various tissues. The Papua New Guinea community is seen as a self-reliant, self-contained, socially cohesive subsistence society whose members are well adapted to their physical and social environment, free from major degenerative cardiovascular diseases, with little overt psychiatric illness, but with a heavy burden of infectious disease, with marginal nutritional levels of degenerative disease and disease from psychological stress. It is clear that health, in its fullest sense, is not the prerogative of any one type of society.


Syphilis in Australian aborigines in the northern territory. A marked increase in the incidence of syphilis in Australian Aborigines in the Northern Territory has occurred in recent years. A total of 287 syphilis notifications relating to Aborigines in the north west of the Northern Territory during the 12-month period from June, 1976, to May, 1977, are analysed. An outline of how the Northern Territory Medical Service plans to deal with the situation is described.


Severe pancreaticoduodenal injury.

Severe pancreaticoduodenal injury. A case where a patient suffered major pancreaticoduodenal injury as a result of a road accident and required pancreaticoduodenectomy is described. Investigative procedures are discussed. Emphasis is placed upon the importance of treating such patients in centres with full support facilities, and with experienced and available staff members.


The organization of a human milk bank in a North Q ueensland hospital. The development of a human milk bank with nursing mothers as donors of human milk is described. Breast milk is collected manually, and as aseptically as possible, by the mother in the privacy of her home, and the milk is transported frozen to the milk bank by a member of the Nursing Mothers' Association of Australia. A sample of expressed milk is also collected and sent to the Microbiology Department of the Australian Government Health Laboratory for bacteriological examination. The milk bank is suitably located in the paediatric ward of the Townsville General Hospital. Human milk which has been classed as bacteriologically safe is given untreated to hospitalized infants in preference to formula milk. The result is a human milk bank which is administered under medical and microbiological control.


Coronary risk factor screening and long-term follow up: year 1 of the Sydney Coronary Heart Disease Prevention Programme. Ten thousand self-referred Sydney inhabitants were screened for major coronary risk factors over one year. Individual "problems" were referred to general practitioners for further assessment and treatment. Seventy-four per cent of subjects have attended a general practitioner where relevant. For subjects under 65 years, 29% had unsuspected hyperlipidaemia, 11% had unsuspected hypertension, and 0.6% had unsuspected diabetes. Nineteen per cent of subjects reported a past history of hypertension, of whom 46% appeared to be well-controlled (diastolic blood pressure less than 95 mmHg). The numbers of cigarette smokers fell with increasing age. Considering hyperlipidaemia, hypertension and cigarette smoking in subjects under 40 years of age, 10.4% of males and 4.9% of females had two or more coronary risk factors. Three hundred and fifty-four subjects selected at random, who claimed to be receiving treatment as a result of initial screening were invited for retesting eight and 15 months later. Significant falls were noted in body weight, blood pressure, and plasma cholesterol readings.


Control of oral anticoagulants by the prothrombin time: a plea for uniformity. Six trromboplastins commonly used for prothrombin time determinations were studied. Prothrombin times of patients who were receiving oral anticoagulant therapy varied widely, depending on the origin of the thromboplastins. The therapeutic range which is recommended with one thromboplastin is often quite different from that recommended with another, and as a result, the therapeutic ranges of different institutions may show no overlap. Management of patients and comparison of therapeutic results would be facilitated if all thromboplastins in use in Australia were standardized by comparison with the Australian Reference Thromboplastin.


Changing mortality from ischaemic heart disease and acute myocardial infarction. From 1969 to 1976 there was a significant reduction in mortality for various forms of ischaemic heart disease (IHD) in inpatients at the Royal Adelaide Hospital. The mortality rate for all forms of IHD fell from 22.9% to 8.8% in men, and from 26.7% to 14.5% in women; the rate for acute myocardial infarction fell from 28.5% to 16.1% in men, and from 38.4% to 25.1% in women; and the mortality rate for chronic IHD fell from 13.2% to 1.1% in men, and from 13.8% to 2.0% in women. A less marked decrease in mortality from acute myocardial infarction occurred in the general population. Numbers of hospital patients increased within each category of IHD. Admission of patients with less severe illness and changes in age and sex distribution may partially account for the observed reduction in hospital mortality.


Perhexiline maleate neurotoxicity and weight loss. Ten Caucasian patients with perhexiline maleate neurotoxicosis and weight loss are presented. Weight loss preceded symptomatic neuropathy which was detected on electromyography in one patient. Weight loss and neuropathy may be marked, but clinical improvement follows drug withdrawal.


Ocular manifestations and complications of acute methyl alcohol intoxication. The ocular manifestations of acute methyl alcohol intoxication were studied in 24 men during an outbreak in Port Moresby, Papua New Guinea. The visual acuity, pupillary reactions to light, fundal appearances and visual fields were recorded in all patients within 72 hours of ingestion of methanol and again three months later. Three groups were identified. Nine patients had no ocular abnormality (Group 1). Seven patients had only transient ocular abnormalities (Group 2). Eight patients had permanent ocular abnormalities (Group 3). Transient abnormalities included peripapillary oedema, optic disc hyperaemia, diminished pupillary reactions to light, and central scotomata. Permanent ocular abnormalities included optic disc pallor, attenuation of arterioles, sheathing of arterioles, diminished pupillary reaction to light, diminished visual acuity, central scotomata, and other nerve fibre bundle defects. Complete blindness occurred in two patients, while severe visula deficit resulted in four others. The incidence of permanent ocular abnormalities was found to correlate with the incidence of metabolic acidosis (P less than 0.01), and with the stated volume of methanol consumed (P less than 0.05). An inverse correlation was found between stated volume of methanol consumed and onset of blurred vision. The difficulties in management and rehabilitation of these patients are discussed.


Coronary artery disease in young Australian women. Over a 12-year period, from 1965 to 1977, 43 women under 46 years of age were documented with angiographic evidence of coronary atherosclerosis at St Vincent's Hospital, Sydney. Twenty-five of the women were able to be followed up at a mean interval of 31 months. This group of young women with coronary artery disease was compared with an age-matched control group of 660 "healthy" women drawn from the general population. Hyperlipidaemia was present in 72% of patients and in 13% of controls. Seventy-three percent of patients were regular cigarette smokers compared with 21% of controls. Only one patient out of 43 showed neither hyperlipikaemia, nor hypertension, nor smoked cigarettes, and multiple risk factors were commonly present. The level of high density or alpha-lipoprotein was significantly reduced in young women with coronary artery disease. These results highlight the presence of classical risk factors in these young women, as well as the importance of alpha-lipoproteins.


Hypertension after ingestion of Trimolets. A 21-year-old nurse presented with severe headache after ingesting one phenylpropanolamine (Trimolets) tablet. Examination revealed hypertension. Although no specific therapy was administered to the patient, her blood pressure normalized within a few hours of admission to hospital and has remained normal since. The patient declined rechallenge with the suspected drug.


Traumatic renal arteriovenous fistula.

Traumatic renal arteriovenous fistula. A case of a 29-year-old man who developed a renal arteriovenous fistula after a gunshot injury is reported. The patient presented with renovascular hypertension associated with high putput cardiac failure, both of which were reversed by surgery.


Carcinoma of the prostate with rectal symptoms. An unusual case of a carcinoma of the prostate where the patient presented with rectal symptoms is described. A good initial response to oestrogen therapy occurred, with loss of perineal pain and rectal bleeding an improvement in urinary stream.


Cold-sensitivity of a double mutant strain combining two ribosomal mutations in the ascomycete Podospora anserina. A double mutant strain combining two ribosomal mutations conferring resistance to cycloheximide exhibits a cold-sensitive phenotype. At low temperature the biosynthesis of the 60S subunit is impaired. Genetic analysis of cold-resistant revertants have shown that this double mutant strain can be used efficiently to isolate new ribosomal mutations.


Localization of 4S RNA genes on the chloroplast genome of Chlamydomonas reinhardii. The genes coding for 4S RNA have been localized on the physical map of the chloroplast genome of Chlamydomonas reinhardii by hybridizing 32P-labelled 4S RNA to EcoRI, BamHI, Bg1II and Hind III chloroplast DNA digests and to hybrid plasmids containing EcoRI and Bam HI chloroplast DNA fragments. At least 10 EcoRI and 7 Bam HI fragments carry sequences coding for 4S RNA. These genes are interspersed throughout the genome. The spacer between the 16S and 23S ribosomal RNA genes, which is repeated twice per chloroplast DNA molecule, codes for at least one 4S RNA, shown to be transcribed from the same strand as the ribosomal RNAs.


Evidence for a near UV-induced photoproduct of 5-hydroxymethylcytosine in bacteriophage T4 that can be recognized by endonuclease V. Non-photoreactivable endonuclease V-sensitive sites have been detected in the DNA of wild type bacteriophage T4 irradiated with near UV light (320 nm). Such sites were not detected in the DNA of (a) wild type T4 irradiated with far UV (254 nm) or (B) in T4 mutants in which non-glucosylated 5-hydroxy-methylcytosine (5HMC) or cytosine replaces glucosylated 5HMC normally present in T4, irradiated with 320 nm or 254 nm light. Although the non-photoreactivable sites accounted for approximately 50% of the endonuclease V-sensitive sites in the DNA of glucosylated T4 irradiated with near UV, there was very little difference in the sensitivities of T4 containing glucosylated 5HMC, non-glucosylated 5HMC and cytosine to near UV (313 nm). We propose that the photoproduct responsible for the non-photoreactivable, but endonuclease V-sensitive, sites in glucosylated DNA is formed from glucosylated 5HMC and that a similar photoproduct is formed from non-glucosylated 5HMC or cytosine in the appropriate phage strains. We further propose that the glucosylated 5HMC photoproduct is non-photoreactivable whereas the cytosine and non-glucosylated 5HMC photoproducts are photoreactivable and are therefore possibly cyclobutane dimers.


Reversible tenfod reduction in mitochondria DNA content of human cells treated with ethidium bromide. Cells of the human line VA2-B in suspension culture have been treated with very low concentrations of ethidium bromide for the purpose of reducing the amount of mitochondrial DNA (mit-DNA) per cell. Cells maintained in the presence of 5 ng/ml ethidium bromide grew at a normal rate for three days; thereafter, their doubling time gradually increased to a stable value of about 60 h. In these cells, the rate of 3H thymidine incorporation into mit-DNA decreased very rapidly to approximately 60% of the normal, and remained thereafter at this level, while the amount of mit-DNA per cell stabilized around a level of 70--80% of the control. In cells long-term treated with 5 ng/ml ethidium bromide, the rate of mitochondrial protein synthesis was about 35% of the normal, and the cytochrome c oxidase activity about 50% of the control. Cells treated with 20 ng/ml of the drug underwent 3--4 cell doublings at control rates, then gradually stopped growing, and eventually died. In these cells, the rate of incorporation of 3H thymidine into mit-DNA was reduced to 50% of the control value after 10 min treatment with ethidium bromide, and became barely detectable after three cell doublings. At this time, the cells had on the average less than 10% of the control amount of mit-DNA, the rate of mitochondrial protein synthesis was reduced to 3% of the normal, and the specific activities of cytochrome c oxidase and rutamycin-sensitive ATPase were less than 20% of the control values. In spite of these marked changes, the cells exhibited only a 20--30% loss in cell viability, as estimated by cloning efficiency, after three days of exposure to the drug. Cells treated with ethidium bromide at 20 ng/ml for three days, and then transferred to drug-free medium, recovered a near-to-normal growth rate and cloning efficiency and a near-to-normal rate of synthesis and amount of mit-DNA in about five days.


Characterization of temperature-sensitive mutants of bacteriophage PM2: membrane mutants. In an effort to understand the genetic regulation of membrane morphogenesis, twenty-nine temperature-sensitive mutants of the membrane-containing bacteriophage PM2 were isolated. Characterization at restrictive temperature revealed groups showing no lysis (Groups I--IV), partial lysis (Groups V--VIII), and full lysis (groups IX--XII) of the host Pseudomonas BAL-31. When the cell lysis data are considered in conjunction with data on stimulation of viral DNA synthesis, at least six mutant groups are defined. Analysis by gel electrophoresis of the pattern of viral proteins synthesized under restrictive conditions further divides the mutants into twelve groups. Temperature shift experiments delineate early, intermediate and late mutants. Complementation data support some of these groupings. The observed low levels of complementation and recombination are discussed in terms of gene product/genome restriction, bound to the membrane at the site of infection. It is of particular interest to membrane morphogenesis that under restrictive conditions late mutants in Groups II, III and IV make empty-appearing vesicles inside the cell that are the size of virus membranes as seen in thin sections of cells in the electron microscope. Mutants ts 1 (Group II) and ts 12 (Group III) show defects in their ability to incorporate into membranes viral structural proteins sp 13 and sp 6.6. The possibility is discussed that either of these proteins control the size and shape of the viral membrane.


Comparative properties of rat liver chromatin in situ and in vitro at early stages after partial hepatectomy. The binding of acridine orange and ethidium bromide to rat liver chromatin increases by 30% one hour after partial hepatectomy, returns to the control level by the second hour and increases again by the sixth hour. The changes described were found in investigations carried out on whole cells, on isolated nuclei, and on chromatin preparation in vitro. Increased ligand binding disappears after the treatment of the one-hour chromatin with a 0.3 M NaCl solution, but such a treatment does not change the binding of ligands to chromatin obtained six hours after hepatectomy. The one-hour chromatin is characterized by elongation of distances between individual nucleosomes whereas the two-hour chromatin is the same as in control.


Effects of chloramphenicol on the postreplication repair and sister recombinational DNA exchanges in ultraviolet-irradiated Micrococcus luteus. The filling of about one third of postreplication DNA gaps in u.v.-irradiated Micrococcus luteus ATCC 4698 is blocked by chloramphenicol (CA) added just before irradiation. Addition of CA 15 min after u.v.-irradiation does not prevent the complete repair of the gaps. U.v.-sensitive M. luteus mutants (ML 6 and ML 15) are identified as defective in different steps of inducible postreplication DNA repair (PRR). PRR in unexcising M. luteus strain G7 is accompanied by the transfer of about 20% of pyrimidine dimers from parental to daughter DNA strands, which indicates the existance of recombinational pathway of PRR. Recombinational PRR in M. luteus is not inhibited by CA.


Cleavage of pre-mRNA sequences by ribonucleases bound to nuclear RNP particles of rat liver. The 30S nuclear RNP particles from rat liver have been shown to split the double-stranded- (ds) and single-stranded (ss) sequences of nuclear pre-mRNA. Experiments performed in vitro have demonstrated that 1) a 5'-exonuclease and an endonuclease specific for double-stranded pre-mRNA sequences exist in the 30S pre-mRNP particles; 2) in dsRNA monophosphorylated 5'-termini arose in the course of incubation with 30S RNP and most of the products remained double-stranded. The analysis of terminal pNp nucleotides revealed a relatively high ratio of pPyp in the cleaved dsRNA, whereas the nucleosides in 5'-terminal pNp of ssRNA showed nearly random distribution. Our results provide a possible explanation for the appearance of pNp termini during the processing of nuclear pre-mRNA of mammalian cells.


Organization, replication and modification of the human genome: differential methylation of two classes of HeLa nuclear DNA separated on Ag+--Cs2SO4 gradients. HeLa nuclear DNA sediments as a single peak, in neutral CsCl, while it is separated in a heavier and a lighter components, in alkaline Ag+--Cs2SO4. The heavy fraction, on the average, represents about 20% of the total DNA. CsCl analytical ultracentrifugation shows that heavy DNA bands at 1.715 g/cm3 and contains 53% GC (10% of the total GC), whereas light DNA bands at 1.703 g/cm3 and contains 40% GC (32% of the total GC). Coherently, Tm values in 0.1 x SSC are 82.5 degrees C, for heavy DNA, and 72.5 degrees C, for light DNA. After treatment with [3H-methyl-S-adenosyl-L-methionine in isolated nuclei, the concentration of labelled 5-methylcytosine was found to be highest in the more dense regions of the heavy peak and in the less dense regions of the light peak. Exposure to ultrasound modifies the quantitative relationship of the two peaks and improves the separation of supermethylated AT- and GC-rich DNAs. Four possible triplets as sites for DNA-methylase recognition are discussed.


A new high sensitive analytical micro-scale procedure for chromosomal proteins. Utilizing male rat liver cells we describe a method for isolating and fractionating chromosomal proteins. About 99% of chromosomal proteins was dissociated using a three step dissociation procedure. DNA was removed by sedimentation and the histone fractions were separated from the non-histone chromosomal proteins by Bio Rex 70 chromatography. The non-histone chromosomal proteins were fractionated by micro-gradient electrophoresis on SDS-polyacrylamide gels, which proved to be superior to the electrophoretic procedures currently in use. The histones were further separated on polyacrylamide-SDS slab gels using a micro-two-dimensional electrophoretic system. The high resolution of these fractionation procedures greatly enhances the possibility of observing small changes in proteins which may play a role in gene regulation.


The effect of the messenger RNA concentration on the competitive inhibition of translation by cap-analogues. Inhibition of translation of several mRNA species in a micrococcal nuclease treated reticulocyte lysate by cap analogues was compared with the competition between two mRNAs. Inhibition characteristics were very similar, only complete mRNA molecules inhibited at concentrations 150 times lower than m7 G5'ppp5'G. The inhibition of mRNA translation by cap analogues could be neutralized by the addition of extra mRNA in a manner predicted from the competitive nature of the inhibition by cap analogues.


Separation of nucleosomes containing histones H1 and H5. Hen erythrocyte chromatin was digested with staphylococcal nuclease and fractionated by electrophoresis in polyacrylamide gels. Instead of the three bands described for mouse carcinoma chromatin, four main discrete components (MN1, MN2, MN2E  and MN3) were resolved in the mononucleosome fraction of erythrocyte chromatin. MN2 contained all five histones and a DNA fragment of 165--180 base pairs. MN2E comprised four nucleosomal histones plus histone H5 (but not H1) and a DNA fragment of 170--190 base pairs. The relatively nuclease resistant MN3 fraction of erythrocyte nucleosomes contained H1 but no H5 histone. A more accurate analysis of the MN2 fraction in mouse carcinoma nucleosomes revealed some additional microheterogeneity depending on the presence of two different subfractions of H1.


[Spectral-luminescent properties of separate aggregated forms of pigments in solutions]. The aggregated forms of protochlorophyll a (PChl), 4-vinyl-protochlorophyll a (4VPChl) and chlorophyll a (Chl) in binar mixtures of dioxane-water was investigated. The aggregates are oligomer particles of pigment molecules having considerable degrees of fluorescence polarisation which points to their ordered structure. Two types of fluorescent associates I and II have been discovered. By its electronic spectrum I is similar to the molecular pigment but has smaller quantum yield B congruent to 10(-2) and the lifetime of fluorescence tau congruent to 3--4.10(-9) sec. Associates of type I spontaneously transform into associates  of type II which have narrower bands of electronic spectrum than the monomer, very low B congruent to 10(-3)--10(-4) and tau congruent to 2--4.10(-10) sec. In contrast with the decreasing of B and the band intensities in CD spectrum conditioned by rotational strength increase by factor of 100 under transformation from I to II. It follows from these data that the antibatic connection possibly exists between excitation deactivation in associates and their optical activity. From data on splitting the associate CD spectra of type I and II the excitation interaction energy V12 congruent to 75 cm-1 was estimated. The reasons of increasing of rotational strength under transformation from I to II and the overturn of the sign dependence of bands in CD spectrum in some cases are discussed.


[Modification of the retina photoreceptor membranes and temperature stability of rhodopsin]. The effect of modification of photoreceptor membranes of the bovine retina on the termodynamical parameters that characterize heat denaturation of rodopsin was studied. The highest increase of the rate constant and the corresponding maximal drop of the free energy change of heat denaturation of the pigment were obtained by using 7 M urea or 25% Triton X-100 in the presence of 5.10(-4) M EDTA. After chipping off one third of the protein from the rodopsin molecule by papain treatment a significant decrease of the slope of the Arrenius curve and a maximal decrease of entropy change compared to the parameters known for heat denaturation of the pigment in native photoreceptor membranes were found. Modification of the lipid components of the photoreceptor membranes (treatment with Triton X-100 and phospholipase C) reduced the thermostability of rodopsin. Maximal changes were obtained at Triton X-100 concentrations 0.1--1%, further concentration increas (1--25%) did not lead to significant changes. Phospholipase C treatment resulted in a decrease of free energy change and an increase of entropy change without affecting entalpy changes, accompaning the heat denaturation of rodopsin. Bivalent cations (Ca2+, Mg2+) increased the termostability of rodopsin both in photoreceptor membranes and in solutions to 25% Triton X-100.


[ESR study of electron transport in photosynthetic systems. VII. Effects of temperature on the processes of electron transport between two photosystems and the structural state of the chloroplast membrane]. Redox transients of P700 in bean chloroplasts induced by far-red continuous light and brief flashes (t1/2 = 7 musec) of white light were studied under various temperatures. It has been shown that light-induced electron transport between two photosystems occurs at temperatures from -5 degrees to 45 degrees. At temperature interval 5 divided by 30 degrees photosystem 2 donates electrons to P700+ in response to the flash with the maximum efficiency. The number of electrons donated from photosystem 2 does not depend on the temperature in the range 5 divided by 30 degrees. The rate of electron transport between photosystems increases when the temperature is increased from -5 degrees to 20 degrees and does not depend on the temperature above 20 degrees. Structural states of the lipid region of the thylakoid membrane were studied by the spin label method. It was shown that the flexibility and the rate of molecular motion of different spin-labeled fatty acids were increased after temperature variations from -10 degrees to 50 degrees. A correlation between the structural state of the lipid region of thylakoid membrane and the rate of electron transport was found.


[Unwinding effect of F1 gene 5 protein on double-stranded polynucleotides and DNA]. The effect of gene 5 protein from bacteriophage f1 on melting of double-stranded polynucleotides and DNAs has been investigated using the UV-spectroscopy method. A dependence of the melting temperature of polynucleotide (DNA)-gene 5 protein complexes upon the polynucleotide (DNA) GC-pair content has been detected. Using experimental data and examining some model systems we came to the supposition that the lowering of melting temperature of polynucleotide (DNA) induced by this protein is probably stipulated by intercalation of the protein tyrosyl residues into one of the chains of polynucleotide (DNA) double helix.


[Molecular mechanism of muscle contraction: the straightening of the bent actomyosin bond]. A new molecular mechanism of muscle contraction is considered based on the cyclochelate oxyphosphorane structure of the long-lived intermediate in myosin-catalyzed ATP. Mg hydrolysis proposed earlier by the author. The mechanism implies the steric cleavage of the actomyosin bond by the gamma-phosphoryl group of ATP.Mg tightly binding to myosin; the myosin-catalyzed addition of water to the gamma-phosphoryl group to give oxyphosphorane group which sterically allows the formation of a more weak bent (deformed) actomyosin bond; the actin-catalyzed breakdown of the tightly bound oxyphosphorane intermediate into weakly bound products; the straightening of the bent actomyosin bond with the active change of an angle of myosin head attachment, the liberation of the weakly bound products and the displacement of the actin filament. The data are given in favour of an oxyphosphorane structure of the long-lived intermediate.