Effect of experimental ischemia on neurotransmitter amines in the gerbil brain. In the gerbil cerebral infarction was produced by unilateral carotid ligation. 3.5 hours later, when the neurological deficit was fully developed, hemisphere dopamine (DA) showed little change from normal. It seems unlikely that changes in DA are the direct cause of the turning behavior shown by these animals. Slight changes in norepinephrine (NE) occurred on the operated side but 4 hydroxy-3-methoxy phenyl-ethyleneglycol sulphate (MOPEG-SO4) levels were not affected. Significant falls in 5-hydroxytryptamine (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) were found on the operated side but there was also a trend for both 5HT and 5-HIAA to fall on the unoperated side. These changes occurred in clincally affected and unaffected animals and their clinical significance is unproven.


Purification and properties of glucose-6-phosphate dehydrogenase from Leishmania tropical promastigotes. Glucose-6-phosphate dehydrogenase specific for NADP (EC 1.1.1.49) was purified to homogeneity from Leishmania tropica promastigotes. The enzyme was found to exist as dimer. The molecular weight of the native enzyme was determined to be 110 000, that of the subunit to be 55 000. The occurence of isoenzymes was demonstrated by isoelectrofocusing. Isoelectric points of glucose-6-phosphate dehydrogenase activity were found at pH 5.5 and pH 6.8. The isoenzymes do not differ with respect to Michaelis constants. The Km-values for NADP and glucose-6-phosphate were determined to be 0.012 mM and 0.15 mM respectively. Glucose-6-phosphate dehydrogenase activity was found to be regulated by product inhibition. The inhibition constant for NADPH was calculated to be 0.05 mM.


Oxygen tension measurements in the intervertebral disc. A methodological and experimental study. A polarographic membrane-covered electrode has been used for measurements of oxygen tension in the intervertebral disc. In vitro studies showed that the method measured partial pressures of oxygen with good reproducibility. However, in long continuous experiments, disc matrix adhering to the membrane influenced the readings negatively. The results of in vivo measurements in canine nucleus pulposus showed tensions of the order of 0.53 - 1.06 KPa (4 - 8 mm Hg). No significant variations between different disc levels were found.


New method of diagnosing neurogenic dysfunction of bladder in candidates for urinary undiversion. Denervation supersensitivity of urethra to alpha-agonist. Testing for denervation supersensitivity response of the urethra to alpha-agonist as a means of excluding neurogenic vesical dysfunction prior to planning undiversion is discussed in a case report. The method is specifically applicable to the bladder that has shrunk from disuse or fibrosis and therefore is not amenable to conventional bladder function studies.


[The influence of ritodrine-hcl (prepar), bunitrolol (stresson) and oxytocin (syntocinon) on Uteroplacental perfusion (author's transl)]. The administration of betamimetics has proved to be useful for symptom-oriented treatment in patients with reduced utero-placental flow. In order to quantify the betamimetic effect flow measurements were carried out in a total of 12 sheep, yielding the following experimental results: 1) Betamimetics, up to a certain point which correlates with maternal heart rate, raise the uteroplacental flow-rate. 2) The use of cardio-selective betablocker prevents undesired betamimetic side-effects but there is also a loss of the rise in utero-placental flow rate. 3) In sheep pretreated with Oxytoxin the application of betamimetics not only offsets oxytoxin-action but also greatly improves utero-placental blood flow.


[Caesarean section: low transverse (pfannenstiel) or midline incision? (author's transl)]. In 67 elective Caesarean sections and 70 emergency sections the effect of the duration of anaesthesia upon the condition of the newborn was examined. The induction-delivery time (IDT), the operation time (OT), and the difference between these, delta t, were correlated with the 1-, 5- and 10-minute Apgar scores and the pH's of the venous and arterial umbilical cord blood. A highly significant negative association was found for the pH in the umbilical vein and delta t in the series of primary sections. Analysis of the emergency sections showed a negative association between the operation time and the 5 minute Apgar score, and a positive association between the delta t and 1 minute Apgar score. Despite these findings we have observed that the induction-delivery time which we are able to achieve in our hospital has no negative effect upon the biochemical condition (pH) of the newborn. A comparison of 619 sections performed by low midline incision with 328 section by Pfannenstiel incision showed no difference with regard to postoperative complications such as disturbance in wound healing or haematoma formation. In conclusion, with respect to the IDT and postoperative complications we have found no contraindication to the use of the low transverse Pfannenstiel incision for Caesarean section.


[Persistence of the oviduct (pseudohermaphroditismus masculinus internus)]. Internal male pseudohermaphroditism is a rare malformation. Its reason is the lack of the Müllerian inhibiting substance produced by the fetal Sertoli cells. Therefore, additional female genital organs exist in a normal male. Genetic determination seems to be possible. Early correction of cryptorch testes is the therapy of choice and promises fertility for some patients.


[Influence on the programmed labour of some perinatological parameter (author's transl)]. In a critical analysis the obstetric results of individual induced labour (socalled "programmed labour") are compared with a series of births with spontaneous start of labour and of indicated induced deliveries. The results shows a much superior outcome of programmed labour: a shorter period of labour, a much reduced number of cesarean sections, a lower frequency of hypoxia, fewer newborn with pronounced Clifford-signs. The technical, personal and organisational efforts in modern obstetric is enormous increased. The induced labour is a possibility, this efforts to put into practice.


[Selection of therapeutic tactics in alcoholic delirium]. The author analyzed the effectivity of the treatment in 602 patients with delirium tremens observed for three years. The first group, 395 patients, received along with the desintoxicational therapy-neuroleptics (aminazin, tizercin, haloperidol). In the second group (207 patients) the treatment was carried out without neuroleptics, the patients received massive desintoxication in the form of drop infusions of solutions with the inclusion of tranquilizers as well (seduxen). The indices of lethality and the average duration of the stay in hospitals were used as criteria of the treatment efficiency. In the second group these indices were much lower: lethality -- 4,4 times less, the duration of the treatment twice less. The data obtained testify against the use of neuroleptics in the treatment of delirium tremens.


Acid phosphatase from liver of the frog Rana esculenta, separation and partial characterization of multiple forms. 1. Acid phosphatase (AcPase) from liver of the frog, Rana esculenta has been isolated and purified. The enzyme is heterogeneous, showing 4 activity zones on disc electrophoresis. The AcPase was separated into 3 peaks on DEAE-cellulose. Peak A corresponding to the electrophoretic AcPase IV represents an extensively purified enzyme form. 2. The separated enzyme forms are change isomers with a molecular weight of about 33,000. They differ markedly in substrate requirements and sensitivity towards activators and inhibitors. All of them are highly activated by dithiothreitol, show a rather restricted substrate specificity, and marked activity against ATP.


Effect of non-carbonic acidosis on total splanchnic perfusion and cardiac output during anaesthesia with O2-N2O-barbiturate-relaxant. Seven dogs were anaesthetized using mebumal natrium-O2-N2O-gallamonijdidum. The PaCO2 was kept at a constant level by means of mechanical ventilation, and non-carbonic acidosis was induced with HCl infusion (0.3 normal). The arterial pH varied from 7.45 to 6.88. During this acidosis, a rising arterio-venous oxygen difference was observed, with an unchanged total oxygen consumption. The pulse fell, but the mean pressures in the right atrium and aorta were unchanged. The peripheral resistance rose by 50%, whereas the fall in cardiac output of 20% was non-significant (0.10 greater than P greater than 0.05). The total splanchnic perfusion fell by 28%, and the change in flow was correlated to the change in pH. Total splanchnic perfusion (ml min-1) = -4078+655x pH (N = 42, r = 0.67, P less than 0.001). Total splanchnic perfusion as a fraction of the cardiac output remained unchanged. The resistance in the splanchnic area rose by 50%. The oxygen saturation in the portal vein and mixed venous blood changed in parallel. It is concluded that contraction of the blood vessels is the most important effect on the circulation resulting from non-carbonic acidosis during the anaesthesia employed here.


Effect of non-carbonic acidosis on total splanchnic perfusion and cardiac output during anaesthesia with O2-N2O-halothane. Six dogs, premedicated with pethidine 10 mg kg-1 b.w, were anaesthetized with mebumal natrium (NFN) 25 mg kg-1 b.w. and 80 mg gallamoni jodidum (NFN). Anaesthesia was continued with O2-N2O-halothane and artificial ventilation. Non-carbonic acidosis was induced by i.v. infusion of hydrochloric acid, during which the related values of pulse, blood pressure, cardiac output, total splanchnic prefusion and portal pressure were measured. The pulse remained unchanged down to pH 7.0. At this pH, arrhythmia suddenly occured and developed into ventricular fibrillation. Before this occured falling cardiac output was observed (cardiac output 1 min-1 = -21.49+3.21 x pH, N = 23, r = 0.75, P less than 0.001) and rising oxygen consumption (O2 ml min-1 kg-1 = 25.79--2.96 x pH, N =28, r = 0.52, P less than 0.01), rising oxygen extraction and rising peripheral resistance, while the mean pressure in the aorta was almost unaltered. During this course towards circulatory failure, an unchanged to slightly rising total splanchnic perfusion (Qsp1) was demonstrated, which with the lowest pH, represented up to 40% of the cardiac output (Qtot): Qsp1/Qtot = 3.11--0.39 x pH (N = 28, r = 0.52, P less than 0.01). Portal pressure rises slightly during acidosis, and oxygen saturation in the portal vein is high. It is probable that the retained splanchnic blood flow is caused by retention of the portal flow. This is quite different from observations during anaesthesia with barbiturates. It is concluded that halothane modifies considerably the circulatory response in the systemic circulation and the splanchnic region during non-carbonic acidosis.


Effects of 3 months frequent consumption of hydrogenated starch hydrolysate (Lycasin), maltitol, sorbitol and xylitol on human dental plaque. Lozenges containing hydrogenated starch hydrolysate (Lycasin), maltitol, sorbitol or xylitol were consumed 4 times daily during 3 months by 4 groups of persons (in all 85 subjects). In the maltitol-, sorbitol- and xylitol-group the plque wet weights were of the same magnitude before and after the test period. In the Lycasin-group, a higher value was found after than before the 3-month period (p less than 0.01). The acid production in suspensions of dental plaque material from Lycasin, maltitol and sorbitol expressed as per cent of that from glucose was approximately the same before and after the test period. From xylitol no acid production could be demonstrated either before or after the 3-month period. There were no statistically significant differences between the plaque pH-changes induced by rinsing with 50% solutions of Lycasin, maltitol, sorbitol or xylitol before and after the test period. However, there was a tendency (p less than 0.05) towards lower pH-values induced by the maltitrol and sorbitol rinse after the 3-month period compared with before. No difference in the relative numbers of facultative anaerobic streptococci. Streptococcus mutans or facultative anaerobic lactobacilli before and after the test period was found.


The prognosis of near-drowned children.

The prognosis of near-drowned children. Thirty children were treated for near-drowning in the Children's Hospital, University of Helsinki during 1971--1976. The patients were divided into 3 groups according to the prognosis: group I included 13 children (43%) with a favourable prognosis, group II four children (13%) with a less favourable prognosis who developed severe sequelae, and group III  13 children with poor prognosis and in whom the subsequent outcome proved fatal. The surviving children underwent neurological, neurophysiological and psychological examination 6--58 months after the accident. The children in group I had slight neurological or psychological signs, some children presented a lowered intellectual functioning level. The children in group II were tetraplegic, unable to speak and had convulsions. The following factors were important in affecting prognosis: the longer the immersion time, the worse the prognosis. However, prognosis could still be favourable with an immersion-time of 11-20 min. Prognosis was bad if the first pH value was less than 7.00. The arterial oxygen pressure values measured during the treatment did not correlate with the prognosis but a low rectal temperature on admission was usually associated with a bad prognosis. The degree of EEG-disturbance had a prognostic value. However, the follow-up recording correlated better with the prognosis than the recordings during the first 24 hours, after which worsening of the EEG sometimes showed a progressive brain lesion.


The effect of propranolol on cerebral oxygen consumption and blood flow in the rat: measurements during normocapnia and hypercapnia. The cerebral blood flow (CBF) and cerebral oxygen consumption (CMRO2) in the rat during normocapnia and hypercapnia were investigated by means of the intraarterial 133Xenon injection technique; measurements were performed during normocapnia and hypercapnia and the effect of propranolol upon CBF and CMRO2 was studied. The CBF technique applied to rat yield reliable results even in high flow situations. A steady state period of only 10--15 s is all that is necessary to obtain the initial slope of the 133Xenon clearance curve from which CBF is calculated and measurements may be repeated within minutes. Hypercapnia caused an increase in CMRO2 of 35% which confirms the findings of other investigators. The beta-adrenergic receptor blocker propranolol (2 mg per kg i.v.) prevented this increase and could eliminate an increase in CMRO2 already induced; this indicates that CO2 affects adrenergic mechanisms. Although propranolol eliminated the CMRO2 response to hypercapnia, it only reduced the CBF response; this dissociation of CBF and CMRO2 response occurred probably because the beta-receptor blockage only eliminated a CBF increase mediated through an increased CMRO2 (cellular response) whereas a direct CO2 effect upon the arterioles (vascular response) persisted.


[Contribution of biology to nosology of depressive states. Neurochemical, endocrine and genetic factors (author's transl)]. Genetic factors have been evidenced in the etiology of manic-depressive syndromes through twins, morbidity risk studies, linkage studies with genetic markers such as color blindness and the Xga blood group, as well as through adoption studies. Most genetic studies indicate that there is a genetic and biological heterogeneity in manic-depressive illness. Among these manic-depressive syndromes, one group is consistent with a dominant X-linked transmission of the disease. From the neurochemical point of view, most investigators emphasize the importance of cerebral neurotransmitter substances such as catecholamines and indolamines in the pathogenesis of bipolar depressive states. According with this hypothesis, depression is associated with a functional deficit in brain monoamines while mania may be due to an hyperproduction of monoamines. These neuropharmacological studies are of importance because they also have neuroendocrine implications. Some pituitary hormones are secreted under the control of brain monoamines, and they are also implicated in the pathogenesis of depressive states.


The pharmacology of mianserin (Org. GB 94) Leviron, a really different antidepressant. The new tetracyclic antidepressant mianserin was clinically shown to be better than placebo and to have less side-effects than the tricyclic antidepressants. It has neither anticholinergic activity nor is it effective in the classical tests of antidepressant activity based on amine re-uptake inhibition. Mianserin shows clear antidepressant activity in tests with muricide rats, in bulbectomised rats and in the acquired immobility test with rats or mice. Mianserin shows effects indicative of anxiolytic activity in several tests, including those using punishment or conflict paradigms. Mianserin is less toxic on the cardiovascular system than the tricyclic antidepressants and on chronic administration to rats and mice does not produce dependence or abstinence.


Studies on the effect of the anti-phagocytic agent cytochalasin B on Leishmania-macrophage interaction. Mouse peritoneal exudate cells were cultured on coverslips in Eagle's Basal Essential Medium. The adhering cells were infected with promastigotes of three different species of Leishmania. After 8 h incubation, the macrophages were fixed and stained, and a total of one hundred cells were counted. The rates of infection of macrophages were respectively 53.5 +/- 5% for L. enriettii, 52.3 +/- 5% for L. donovani and 11.7 +/- 2% for L. tropica. When cytochalasin B at concentrations of 2.5, 5 and 10 microgram/ml and Leishmania promastigotes were added to the adhering cells at the same time, the drug did not have any effect on the uptake of the organisms by the macrophages. However, when the cells were treated for a 2-h period with the drug and then were infected with the promastigotes, only 1-2% of the cells were infected. On the other hand, when cytochalasin B-treated cells which had lost their phagocytic ability were washed and then were infected with the promastigotes, some degree of cellular infection was observed. It was concluded that infection of mouse p.e.c. by three different species of Leishmania which were used in our study was by phagocytosis rather than active penetration of the organisms into the cells. It was also of interest to note that although our outbred strain of mice gets infected easily with L. tropica, the p.e.c. of these animals phagocytosed L. tropica with least efficiency in comparison with L. donovani and L. enriettii.


Skin-piercing blood-sucking moths II: Studies on a further 3 adult Calyptra [Calpe] sp. (Lepid., Noctuidae). 1. Of the scarce Calyptra minuticornis, C. orthograpta and C. labilis, 51, 24, and 7 adults, respectively, were observed during some 600 night inspections at over 100 sites in 1965--1967 and 1971--1977. 2. Hitherto biologically completely unknown, and not recorded before in S.E. Asia, the latter two species flew in or near tropical monsoon forests in hilly regions (300--600 m) of N. Thailand (C. orthograpta also N. Laos). C. minuticornis was found in these and in tropical evergreen and semi-evergreen rain forests of S. Thailand and N.W. Malaysia. 3. In N. Thailand the three species were more common at the end of the cool season/start of the hot season and at the start of the rainy season. They were active mainly during the first half of the night 4. Flight and piercing behaviour, alighting, resting, enemies, and the lack of females, were similar to virtually identical with the "classical" skin-piercing blood-sucking C. eustrigata. 5. C. labilis was seen attacking elephant, C. orthograpta also water buffalo and sambar, C. minuticornis also zebu and tapir but not sambar. C. minuticornis settled on man also but did not pierce. 6. Through no piercing of hosts' skin has actually been seen in nature, indirect evidence suggests that the 3 moths are likely to be occasional blood-suckers. They pierced and sucked blood from the author's skin in experiments. 7. Reasons for lack of direct evidence may be: less developed hematophagy, less favoured hosts, lack of easy-to-pierce injured skin (which also trigger the piercing response), different climatic and phytoecological environment, fewer specimens than in the case of C. eustrigata. 8. Field observations and experiments indicate that the closely related, fruit-piercing Oraesia emarginata is not skin-piercing blood-sucking--a habit likely to be exhibited mainly in humid equatorial regions by a few Calyptra only.


Peritrophic membrane formation and the midgut barrier to arboviral infection in the mosquito, Culex tarsalis Coquillett (Insecta, Diptera). The formation of the peritrophic membrane in adult female mosquitoes, Culex tarsalis, was examined by light and electron microscopy. The initial evidence of secretion of peritrophic membrane precursors occurred at 8-12 h after ingestion of the bloodmeal. Morphogenesis of the peritrophic membrane occurred within 12-16 h after the initial secretion; culminating with a fibrous, multilayered peritrophic membrane 20-24 h after bloodmeal ingestion. A discussion of the potential participation of the peritrophic membrane in a midgut barrier to infection by arboviruses is presented. The participation of the peritrophic membrane in a midgut barrier to infection of C. tarsalis, and many other mosquito species, by arboviruses is considered a moot point.


The feeding habits and ecology of the tsetse fly Glossina morsitans submorsitans Newstead in relation to nagana transmission in the Gambia. The source of blood meals from 174 fed Glossina morsitans submorsitans Newstead, captured in malaise traps in Savanna woodland in The Gambia, were identified by the precipitin test. Warthog accounted for 90% of the meals and single bushbuck and ox feeds were identified. Nagana is a major problem in the area, but contact between tsetse and livestock is reduced by restricted grazing. In this situation, warthog, with a ubiquitous distribution, appear to be major maintenance hosts for G. m. submorsitans as well as a potential reservoir of trypanosomiasis.


Complement activation by parasites. A review. Activation of complement by parasites (living parasites or purified parasite antigens) is involved in several mechanisms of the host parasite relationship. In most of the experiments performed in vitro, complement activation was found to be lethal for the parasites, but sometimes it could be essential for the development of parasitemia. Both classical and alternative complement pathways may be activated by parasites; the classical pathway nearly always requires the involvement of antibodies whereas the alternative pathway is activated directly by products released by the parasites or present in their teguments. Activation of complement, especially via the alternative pathway may also be a prerequisite for cellular adherence to parasites which can then cause their death.


Tsetse movement in wind fields: possible epidemiological and entomological implications for trypanosomiasis and its control. This paper presents evidence that tsetse flies (Glossina) can be dispersed by wind. This dispersal in West Africa is suggested to be along a south-west north-east axis. The implications of wind dispersal of Glossina for chemical and genetic control operations is discussed. Field experiments necessary to test this hypothesis are recommended. A study of human trypanosomiasis foci in West Africa has revealed that foci are orientated in roughly parallel lines in a south-west north-east direction. This directionally was significant when compared with 7 other compass points. It is proposed that foci could be populated by infected flies dispersed from the south west, where denser populations exist, on the prevailing winds in the late dry/early rainy season. The significance of these ideas in relation to the epidemiology of Trypanosoma brucei rhodesiense in Ethiopia and T. evansi are discussed.


A review of helisoma duryi in biological control. Biological control of schistosomiasis by means of introduction of the north American planorbid snail, Helisoma duryi, as a competitor of the intermediate host snails has been proposed. The systematics of the genus Helisoma and the geographic distribution of the different species is described. Papers dealing with laboratory experiments or field observations on the competition between H. duryi and different intermediate host snails have been reviewed. The status of H. duryi as intermediate host of trematodes has been evaluated by searching the literature for all the trematode species that are recorded from the genus Helisoma. The list does not include trematodes of medical or veterinary importance and despite many attempts it has not been possible to infect H. duryi with Schistosoma mansoni and S. haematobium. Finally this paper makes a few comments on the experiments that should be performed in the laboratory, under semifield conditions and and field conditions before H. duryi should be actively dispersed in Africa. The aspects to be considered include the nature of the competitive interactions, the relation between H. duryi and different medical and veterinary important trematodes and the effect of H. duryi on the biotope.


Effect of levamisol on tissues of Ascaris lumbricoides. Levamisol which is highly effective against Ascaris infections, was shown to produce degenerative changes in the intestine and the reproductive system of the worm. Worms that were not expelled by treatment produced only nonviable eggs which could not develop in vitro. Levamisol is thus shown to be not only a highly curative drug, but a compound of significant epidemiological importance.


A communication on health and development in the Kainji Lake area of Nigeria. A study of the health care delivery facilities in the Kainji Lake area of Nigeria (an artificial lake created in 1968) showed that hospitals, a health centre, maternal and child health centres, public health units, dispensaries and leper institutions, controlled by various organizations, are available. Dispensaries and leper settlements/clinics form the most numerous health providers in the rural areas. Analysis of 1973 data from eight dispensaries around Lake Kainji showed that malaria, gastroenteritis, chest and skin infections, venereal diseases and shistosomiasis constitute the major health problems. Observations of the environmental sanitation in the study area by the author support the idea that the diseases emanate particularly from the low standard of environmental health. A suggestion is made for the establishment of a central organization charged with the responsibilities for health planning and development. The evaluation of the impact of hte dispensaries as health providers is needed for future health planning. A health care delivery system supported by operational research should be initiated at the village level.


Influence of the isolation procedure on the structure, neuraminidase and heamagglutinating activities of Sendai virus envelope glycoproteins. The influence of the isolation procedure of Sendai virus glycoproteins from the virus surface on their neuraminidase and haemagglutinating activities, as well as on some structural properties was studied. These glycoproteins exhibited lower specific neuraminidase and haemagglutinating activities than those of intact virus. Neuraminidase activity was expressed when the glycoproteins were constituted in forms with molecular weights of about 70,000 (monomer), 160,000 (dimer), 300,000 (tetramer) or 600,000 (octamer), whereas haemagglutinating activity was only found for the glycoproteins aggregated in a high mol. wt. (approximately 10(6) daltons) form. The isolated glycoproteins contained two subunits revealed by sodium dodecyl sulphate polyacrylamide gel electrophoresis and three distinct antigenic components revealed by rocket immunoelectrophoresis. Different treatments of the glycoproteins after their isolation altered their structure. Consequently either neuraminidase and haemagglutinating activities were signicantly reduced, or one of these activities was not expressed.


Size and shape of mycoplasma virus MV-Lg-L 172 DNA. Sedimentation of DNA of mycoplasma virus MV-Lg-L 172 in neutral and alkaline density gradients showed that the chromosome of this virus is most probably formed by a double-stranded circular DNA molecule with a molecular weight of approx. 10(7) daltons. These results were confirmed by direct electron microscopy of the viral DNA. Gamma-irradiation of the virus caused in its DNA single breaks on the average per each 66 eV of absorbed energy. Virus survival depended exponentially on the irradiation dose, D0 being between 60,000 and 70,000 rads. This dose induced on the average one single break in the DNA.


Comparative studies on poxvirus strains isolated from camels. Five poxvirus strains isolated from camels in Egypt, Iran and the U.S.S.R. were investigated. The morphology and size of the negatively stained virions of the investigated strains were identical. The strains produced minute white pock lesions localized mainly on the infected area of the chorioallantoic membrane, without generalization of lesions or death of embryos. The ceiling temperature and the haemagglutinating activity of the different strains were different. All the strains were apathogenic for rabbit skin and highly pathogenic for mice inoculated intracerebrally. Serologically, all the strains were related to vaccinia virus but with different degrees. The studied strains had the characteristics of members of the genus Orthopoxvirus.


Sikhote-Alin virus, a new member of the cardiovirus group (Picornaviridae) isolated from Ixodes persulcatus ticks in Primorie Region. A virus, designated Sikhote-Alin, was isolated in 1970 from Ixodes persulcatus ticks collected from a wild boar in the Primorie region (U.S.S.R.) Sikhote-Alin virus showed no haemagglutinating activity and no antigenic relationships with arboviruses of 12 antigenic groups, 17 ungrouped tick-borne arboviruses, porcine enteroviruses and coxsackie A (types 1-18) viruses. An one-way antigenic relationship was demonstrated by complement fixation with cardioviruses (Mengo and Columbia-SK strains). The virus contains RNA, is resistant to lipid solvents, highly thermostable in the presence of 1 M MgCl2 and its size is over 20 nm but less than 25 nm. All these properties make it possible to consider it as a new member of the cardiovirus group (genus Enterovirus; Picornaviridae).


Latent pseudorabies virus infection established at supraoptimal temperature. Little or no infectious virus was recovered from BHK-21 cells adapted to 40 degrees C, when they were infected with an attenuated strain of pseudorabies virus (PRV) at low multiplicity of infection (MOI) and subsequently kept at 40 degrees C. By passaging the infected cells at 40 degrees C, infectious virus disappeared within 2-3 passages. When the cells were shifted down to 37 degrees C, activation of virus growth occurred after a latent period of 48-72 hr. Infected cells kept at 40 degrees C were as sensitive to superinfection with the virulent PRV strain TOP as the control cells. The ability of PRV strains to enter into the described latent state was related with the degree of their virulence. When cells were treated with 5-bromo-2-deoxyuridine (BUdR) at 40 degrees C for 24 hr and then shifted to 37 degrees C, a slight increase in the number of infectious centres was observed and the latent period was also prolonged.


Influence of experimental influenza infection of the eye on the course of herpetic keratitis in rabbits. Influenza virus monoinfection and combined influenza and herpes simplex virus (HSV) infection of the eye was studied in rabbits. Influenza A/Hong Kong/1/68 (H3N2) virus caused a clinically overt disease of the eye only after inoculation into the eye chamber. The combined influenza and HSV infection of the eye induced severe iridocyclitis. The combined infection of the eye with influenza virus and HSV had a more severe course than HSV monoinfection. The occurence of influenza antibody in the lacrimal fluid in the presence of the antigen in eye tissues is of diagnostic importance in determining the aetiology of the disease.


Viral superinfection in cells carrying an arenavirus and/or a togavirus. Four lines of the same L-cell clone were transferred 60 times in parallel: uninfected cells, a line carrying lymphocytic choriomeningitis virus (LCMV), another one carrying tick-borne encephalitis virus (TEV) and one carrying both viruses. In double persistency, LCM and TEV were suppressed and stimulated, respectively. Cell multiplication rates were comparable in all four lines. Single LCMV persistence caused marked resistance of L cells to superinfecting viruses from various taxonomic groups, but this phenomenon was abolished or even reversed to increased sensitivity in the cell line with co-persisting LCMV plus TEV.


Chikungunya virus in vivo autointerference associated with a small plaque variant. Virulent and avirulent plaque variants of Chikungunya (CHIK) virus were compared with the prototype and other strains. Interference with infective virus growth or mouse pathogenicity only occurred in the presence of small plaque (SP) variants in homologous systems. Possible mechanisms for this are suggested.


Differences in the susceptibility of mouse lines to the rickettsial pox agent. A definite correlation between the susceptibility of spleen macrophage cultures derived from a highly susceptible mouse line (C57Bl/6) and a line with low susceptibility (DBA/2) and the susceptibility of these mouse lines to infection with Rickettsia acari was established. Intensive replication of the rickettsiae in cultures from highly susceptible animals caused marked disorders in cell metabolism and eventually death of the culture. Cell cultures derived from resistant mice gradually eliminated the rickettsiae by intracellular digestion; necrobiotic changes in them were insignificant.


Experimental infection of Putorius eversmanni polecats and Martes foina martens with Tahyna virus. Three Putorius eversmanni pole-cats and two Martes foina martens aged about 9 months were subcutaneously infected with about 260 suckling mouse LD50 of the extraneurally passaged "236" strain of Tahyna virus (California group, genus Bunyavirus). Viraemia with maximal titres of 1.32 (pole-cats) and 1.28 (martens) dex intraperitoneal (i.p.) mouse LD50/0.02 ml was demonstrated from 48 to 96 hr after inoculation (p.i.). By the plaque-reduction neutralization test, seroconversion was demonstrated 15 days p.i. (from less than 4 to titres of 8192 in pole-cats and 4096 in martens).


Razdan virus, a new ungrouped bunyavirus isolated from Dermacentor marginatus ticks in Armenia. A virus, designated Razdan, was isolated from Dermacentor marginatus ticks in the Armenian S.S.R. in 1973. The complement fixation tests revealed no antigenic relationships to 74 tick-borne arboviruses. The size of the virus is about 100 nm; it agglutinates goose erythrocytes at pH 5.5--7.0, is pathogenic for newborn, 14-day-old and adult white mice and multiplies in primary and continuous cell cultures. Morphological properties of the virus permit its classification as a member of the family Bunyaviridae.


Attempts at demonstration of lipopolysaccharide in phase II Coxiella burnetii. Comparison of some properties of phase I and phase II Coxiella burnetii cells suggests the presence of lipopolysaccharide (LPS) also in the surface structures of phase II cells. Polysaccharide chains were released from them by mild acid hydrolysis and corpuscular residues resulting from such hydrolysis elicited in rabbits anti-lipid A-antibodies. Toxicity for adrenalectomized and actinomycin D-sensitized mice was demonstrated with phase I cells, but not with much higher concentrations of phase II cells. By contrast, the extent of protection against formation of ascitic tumour in mice with comparable concentrations of phase I and phase II cells was similar.


Antigenic glycopolypeptides HA1 and HA2 of influenza virus haemagglutinin. III. Reactivity with human convalescent sera. The immune reactivity to both haemagglutinin glycopolypeptides HA1 and HA2 [prepared from bromelain-released haemagglutinin of influenza virus A/Dunedin/4/73 (H3N2)], was demonstrated by both gel double immundiffusion and radioimmunoassay in human convalescent sera obtained after natural infection during influenza epidemics in 1974/75 and 1976/77. In gel double immunodiffusion, the precipitin line(s) corresponding to glycopolypeptide HA1 were always more distinct than precipin line(s) corresponding to glycopolypeptide HA2. In radioimmunoassay, human convalescent sera revealed higher titres for binding of 125-I-labelled HA2 than for 125-I-labelled HA1. Characterization of human convalescent sera was completed by haemagglutination-inhibition test.


Specific alteration of Sendai virus glycoprotein subunits. The alteration produced by chemical and physical agents in the structure and neuraminidase activity of Sendai virus glycoproteins was studied. While dissociation of glycoproteins with 1% sodium dodecyl sulphate (SDS), 2% beta-mercaptoethanol and 5 M urea for 2 min at 100 degrees C yielded the known HN and F subunits (mol. wts. 60,000 and 53,000), in the presence of 1% SDS the glycoproteins were converted into components with approximate mol. wts. of 60,000, 120, 000 and higher. Treatment of the glycoproteins with 2% beta-mercaptoethanol and 0.1% SDS favoured the formation of a single component with a mol. wt. of 75,000. The alterations in the glycoprotein structure were very likely caused by their free -SH groups content. An average value of 6 free -SH groups per glycoprotein subunit was estimated. Glycoproteins stored at 4 degrees C contained only 53,000 mol. wt. subunits. During storage a kind of conversion of 67,000 to 53,000 mol. wt. components took place, preserving about 60% of the initial neuraminidase activity.


Comparative analysis of interferon and antiviral protein messenger RNAs. A comparative analysis of interferon and antiviral protein messenger RNAs was carried out. Differences in their biological activities and sedimentation coefficients were found. In RNA preparations from superinduced cells (cells treated with poly(I).poly(C) and antimetabolites) and from cells treated with interferon, messenger RNAs possesing interferon and antiviral activities were detected. The results suggest the existence of two types of mRNA (for interferon and antiviral protein, respectively) and support the hypothetic model of interferon action via an antiviral protein.


Light and electron microscope study of the neurotropism of Powassan virus strain P-40. Brains of adult white mice inoculated with the P-40 strain of Powassan virus isolated in Primorsky Krai (U.S.S.R) from ticks were studied by light and electron microscopy. Accumulations of virus particles were found in neurons and their dendrites and axons, in glial cells, and in intercellular spaces. In the nerve cells, most prevalent were changes of the type of chromatolysis and formation of small vacuoles, associated with the alteration of the endoplasmic reticulum induced by virus morphogenesis. In virus-affected cells, multilayer dense membranes were found.


Antiviral activity of certain isatinisothiosemicarbazones against Mengo and vaccinia virus infections in mice. Among eleven isatinisothiosemicarbazones (IITS) examined only 1-ethylisatin-S-n-butylisothiosemicarbazone (ZIMET 189/69) proved to be significantly effective against lethal Mengo and neurovaccinia virus-induced encephalitis in mice when administered subcuaneously (s.c.) in doses of 1 mmole/kg body weight per day. With peroral (p.o.) administration all the drugs failed to prevent mortality in Mengo virus-infected mice. Against this virus ZIMET 189/69 was effective over a concentration range from 0.6-1.4 mmoles/kg per day producing a plateau effect at doses greater than 1 mmole/kg. With Mengo virus maximum protective response was seen in intraperitoneally (i.p.) or intranasally (i.n.) infected mice when treatment was begun at the time of virus inoculation and continued, once daily for a period of at least four consecutive days. Delayed initiation of treatment failed to protect Mengo virus-infected mice but was effective in vaccinia virus-infected mice.


Detection and tissue localization of components of the immune complex in animals infected and immunized with influenza virus. Mice previously vaccinated or convalescents after infection with mouse-adapted influenza virus were challenged by various routes with live or inactivated virus. The components of the immune complex (antigen-antibody-complement) could be detected by immunofluorescence in lungs, kidneys, and heart. The frequency of positive immunofluorescence reaction was related to serum antibody level and, to some extent, to the route the animals were challenged.


Live tissue culture influenza vaccine for oral administration. I. Specific immune response to monovaccine A (H3N2) in volunteers. Oral immunization of volunteers with a live tissue culture influenza A (H3N2) vaccine induced an increase in virus neutralizing (VN), haemagglutination inhibiting (HI) and neuraminidase inhibiting (NI) antibody. The dynamics of antibody and IgM and IgG immunoglobulin formation in the blood depended to a great extent on their prevaccination levels. The highest per cent of seroconversions was observed after the 3rd vaccination: a 4-fold or greater rise of VN antibody was found in 80% (titre increase by 3.0 log2 units), of HI antibody in 70% (titre increase by 2.6 log2 units) and NI antibody in 73% (titre increased by 2.5 log2 units) of the volunteers. The level of IgG increased after each vaccination but its highest level did not coincide in time with the maximum antibody production. High titres of the antibodies studied were recorded 1-2 months after the 3rd vaccination, irrespective of their prevaccination levels.


The influence of temperature and pH on the growth of Rickettsia conorii in irradiated mammalian cells. The temperature range for optimum growth of Rickettsia conorii in suspension culture of gamma-irradiated L cells was 32-38 degrees C, resulting in rickettsial doubling times between 4.1 and 6.0 hr. An asynchronous release of R. conorii from host cells was suggested by the constant increase in percent cells infected over a 36 hr period. Rickettsial growth was optimal at neutral to slightly alkaline extracellular pH levels. A moderately acidic pH, however, resulted in an increase in doubling time from 4.1 to 7.8 hr.


Antibody response in man following a small intradermal inoculation with Coxiella burnetii phase I vaccine. A small inoculum (0.2 microgram) of phase I Coxiella burnetii vaccine given to individuals previously sensitized to CO burnetii elicited a positive skin reaction and a strong IgM phase I antibody response as determined by microagglutination, complement fixation and microimmunofluorescence tests. A similar inoculum administered to nonsensitized individuals did not elitic a skin reaction nor stimulate a recognizable antibody response. Serum from one of these sensitized and skin tested individuals was fractionated by gel filtration methods. The serum and serum fractions were titrated in a mouse seroprotection test using primary chicken embryo cell culture plaque technique as the assay procedure. Results of the mouse seroprotection test indicated that most of the protective activity of the serum was associated with the IgM fraction and that phase I IgM antibody suppressed the growth of C. burnetii in mouse spleen when mixed with the rickettsial suspension prior to inoculation.


Isolation of Tettnang virus from ticks, mosquitoes and small rodents. Seven strains of Tettnang virus were isolated in Czechoslovakia: 3 from Ixodes ricinus tick nymphs, males and females, one from Dermacentor reticulatus tick females, one from Aedes cantans mosquitoes and two strains from the brains of Clethrionomys glareolus and Apodemus flavicollis small rodents.


Antigenic glycopolypeptides HA1 and HA2 of influenza virus haemagglutinin. IV. Immunogenic properties of separated haemagglutinin glycopolypeptides. Highly purified haemagglutinin glycopolypeptides HA1 and HA2 were effective in eliciting an antibody response. HA2 had a markedly greater immunogenic potential than HA1. In gel double immunodiffusion, sera from rabbits immunized with HA2 produced more distinct precipitin lines than sera obtained by immunization with HA1. Both kinds of rabbit sera gave precipitation with homologous antigen and with bromelain-released and purified haemagglutinin (B-HA). In radioimmunoassay, sera from rabbits immunized with HA2 revealed considerable titres for 125I-labelled HA2 binding and reacted preferentially with 125I-labelled HA2. In general, sera from rabbits immunized with HA1 exhibited low titres for 125I-labelled HA1 binding: usually they reacted also with 125I-labelled B-HA and 125I-labelled HA2. Only rabbits injected with a few doses of HA1 at short intervals revealed preferential binding for 125I-labelled HA1. Glycopolypeptides HA1 and HA2 failed to induce haemagglutination-inhibiting and virus neutralizing antibodies in rabbits.


Radiographic manifestations of bone marrow transplantation in children. Radiographically detectable complications in 35 children after bone marrow transplant are reviewed. These complications are most frequently due to infection, chemoradiotherapeutic toxicity, and graft versus host disease (a transplant rejection phenomenon peculiar to bone marrow transplant patients). The pulmonary complications within the first 2 months are secondary to a form of interstitial lung disease. Interstitial lung disease has a strong correlation with graft versus host disease. Extrapulmonary visceral complications include hepatosplenomegaly, nephromegaly, and hemorrhagic cystitis. These are due to graft versus host disease, radiation, and chemotherapeutic toxicities, respectively. Sinusitis, cerebral atrophy, and intracerebral hematomas are less frequent complications. Osteoporosis due to steroids is the single most important osseous complication.


Role of blood platelets in coronary artery disease. Over the past decade, research in blood platelet physiology has led to the suggestion that platelets play an important part in the pathogenesis and complications of coronary artery disease. Occlusive intravascular platelet aggregates have been shown to cause ischemic myocardial damage in the experimental animal and to be present in some patients who die suddenly. The interplay between endothelial damage and platelet aggregation has been implicated in the etiology of atherosclerosis. Products released from platelets during aggregation may cause arterial spasm. Patients with overt ischemic heart disease and with the risk factors associated with coronary artery disease have been found to have abnormally reactive platelets. Clinical studies of drugs that inhibit platelet aggregation have been reported to show a beneficial effect in preventing cardiac deaths or myocardial infarction; other studies have been negative or shown only a trend toward benefit. This report reviews the theoretical and experimental basis for the platelet hypothesis and the current data on the use of antiplatelet drugs in patients with coronary disease.


Fiber of the maize tortilla.

Fiber of the maize tortilla. Fiber concentrations were measured in maize tortillas and in masa, the lime-treated dough from which they are made, with the aid of Van Soest's methods. Neutral detergent fiber of tortillas was 6.60 +/- 0.98% (mean and SD) and acid detergent fiber 3.75 +/- 0.83% of the dry weight corrected for ash. The hemicellulose fraction was 2.89 +/- 0.94%. Both neutral and acid detergent fiber were significantly higher in tortilla than in masa. The gain in fiber by tortillas during baking is attributed to the formation of browning reaction (Maillard) products resistant to the detergent-containing fiber reagents.


Bartter's syndrome. Differentiation into two clinical groups. We were able to separate Bartter's syndrome patients into two groups: Group 1 patients are seen at a young age, with hyponatremia and episodes of extracellular volume contraction. Group 2 patients are older and most have tetany; plasma sodium values and renal sodium balances are normal. Plasma potassium values are lower and plasma renin activity and plasma magnesium levels are higher in group 1 than in group 2. It may be that all patients with Bartter's syndrome manifest the features of both groups, group 1 patients with time developing into group 2 patients. These observations have important implications in the treatment of patients with Bartter's syndrome.


Pharmacologic inhibition of preterm labor. Preterm labor is responsible for a majority of cases of perinatal morbidity and deaths. Prevention of preterm labor is not usually possible; thus pharmacologic treatment is the only recourse available. Numerous agents have been used to treat preterm labor, but none has proved to be superior. This report reviews the current information available about the pharmacology of labor-inhibiting drugs and discusses the clinical approach to the management of preterm labor.


Lower esophageal sphincter pressure during the normal menstrual cycle. Lower esophageal sphincter pressure (LESP), basal gastric pH, and plasma levels of gastrin, estradiol, and progesterone were determined in ten women known to have normal menstrual cycles. All determinations were performed both during the follicular phase (Days 2 to 8) and during the luteal phase (Days 20 to 30). In addition, an intraluminal pH probe placed 5 cm. above the lower esophageal sphincter was used to test for the presence of acid reflux in response to three provocative procedures. LESP during the follicular phase was 19.0 +/- 1.5 mm. Hg (mean +/- S.E.M.) and during the luteal phase 16.5 +/- 1.3 mm. Hg (p less than 0.01). Basal gastric pH and plasma gastrin levels were similar at both times. Plasma estradiol in the follicular phase (76.1 +/- 7.0 pg. per milliliter) increased twofold during the luteal phase (159.0 +/- 6.0) (p less than 0.01). Plasma progesterone increased from a level of 1.5 +/- 0.8 ng. per milliliter during the follicular phase to 19.2 +/- 4.2 during the luteal phase. Coincident with these changes in LESP and increases in steroid levels, acid reflux was detected in five women during the luteal phase but was present in only one during the follicular phase.


Cow red blood cells. II. Stimulation of bovine red cell glycolysis by plasma. Cow red cell glycolysis, which can be stimulated by a variety of purines and pyrimidines, was also found to be elevated by its own plasma. Dialyzed or charcoal-treated plasma could no longer stimulate glycolysis, suggesting that the stimulating factors may be purines or pyrimidines. Determination of purines or pyrimidines in plasma revealed the presence of xanthine (0.31 muM), hypoxanthine (0.60 muM), and adenosine (0.05 muM), as well as unknown compounds. A physiologic level of hypoxanthine, with or without xanthine and adenosine approximating their concentrations in plasma, resulted in the stimulation of cow red cell glycolytic rate by 16% (P less than 0.01). These findings suggest that plasma-borne purines may act on cow red cells in concert with as yet unidentified factors. Moreover, exchanging calf and cow plasmas produced no stimulatory effect on either calf or cow red cell glycolysis, suggesting that a) calf red cells lack some of the cellular components that respond to this stimulator and, b) only cow plasma contains this specific stimulator. In other species, including dog, cat, rabbit, rat, guinea pig, and human, stimulation of glycolysis by plasma was not observed.


Plasma secretin concentrations in fasting and postprandial states in dog. In four dogs with a modified Herrara pancreatic fistula and gastric cannula and three dogs with two duodenal cannulas, ingestion of a meat meal resulted in a significant and sustained increase in the mean plasma immunoreactive secretin concentrations, from mean fasting levels of less than 10 pg/ml to 25--55 pg/ml. This increase in the plasma secretin concentration coincided with a marked increase in pancreatic bicarbonate output and frequent decreases in the mean proximal duodenal pH to less than 4.5 from the range of 6.5 in the fasting state. Intravenous administration of cimetidine, 150 mg, produced a marked suppression of postprandial increases in both pancreatic bicarbonate output and plasma secretin concentration. Moreover, the postprandial duodenal pH rarely reached below 5.0 after cimetidine administration. These studies indicate that plasma secretin concentration does increase significantly after a meal. The postprandial increase in plasma secretin concentration appears to depend on the gastric acid delivered in the proximal duodenum. A possible physiological role of secretin in the pancreatic secretion after a meal is indicated by these findings.


Neonatal gastric motility in dogs: maturation and response to pentagastrin. Postnatal changes in the pH of gastric secretions, gastric motility, serum gastrin concentration, and response of the stomach to pentagastrin administration were studied in 15 beagle puppies from birth to 5 wk of age. Motility was monitored manometrically via twin-lumen catheters 3--6 h postprandially. Mean gastric pH was stable at 5.85 until the 7th postnatal day when pH decreased to 3.45; pH then increased to a mean value of 4.95 through the 18th day. Antral contractions increased from 0.2 contractions per min on the day of birth to a maximum 2.3 contractions per min on the 11th day and then gradually declined. Pentagastrin (8.0 microgram/kg sc) had no effect on gastric pH or motility until the 2nd postnatal wk. Pentagastrin inhibited the rate and peak pressure of antral contractions from the 2nd through the 5th wk. Mean serum gastrin concentrations in six puppies were greater than values for adult dogs, attaining a preweaning maximum on the 9th day.


Effect of gastrin I and gastrin II on canine bile flow. The role of gastrin in the hormonal control of canine hepatic bile flow was evaluated. Because of the importance of the presence of sulfation of the carboxyl terminal peptide in the function of other cholecystokinetic hormones and peptides in the biliary tract, the choleretic properties of sulfated gastrin II were compared to the choleretic properties of nonsulfated gastrin I. Exogenous administration of gastrin I and II to dogs with chronic bile fistulas demonstrated that gastrin II, but not I, significantly increased hepatic bile flow. Chemical stimulation of the release of endogenous gastrin in dogs with denervated antral pouches did not increase hepatic bile flow, whereas a choleresis resulted when the innervated antrum was stimulated. Serum gastrin values obtained during the infusion of gastrin II at doses that produced a choleresis resulted in serum gastrin values that were greater than those produced by a more physiological stimulus, such as chemical antral stimulation. The results of this study suggest that only the sulfated gastrin II, not gastrin I, is a choleretic agent in dogs and only at pharmacological, not physiological doses.


Chronic arteriovenous shunt: evaluation of a model for heart failure in rat. A model for high output heart failure (HCO) was developed in male, Sprague-Dawley rats using an abdominal aortocaval shunt equal to 50% of total cardiac output (CO) with 2 mo of postsurgical recovery. The model was evaluated by analysis of hemodynamics, peripheral blood flows (BF) (radioactive microspheres), and plasma catecholamine levels as well as mass and fluid content of organs. In HCO, CO and left ventricular end-diastolic pressure were increased with significant left and right ventricular hypertrophy. Mean blood pressure (BP) was unchanged, but pulse BP was increased in HCO. BF to skeletal muscle, cutaneous, and some splanchnic regions was reduced to HCO, whereas BF to the cerebral, coronary, and renal beds was protected. Plasma epinephrine and norepinephrine levels were significantly elevated in HCO suggesting enhanced sympathetic as well as adrenal catecholamine release. Tissue analysis indicated altered circulatory status secondary to HCO in liver, kidney, spleen, and lung. The results indicate that this model will be a relevant tool for studies of the circulatory effects of heart failure.


Effect of Krebs cycle intermediates and inhibitors on toad gastric mucosa. An attempt to increase the permeability of gastric mucosa to exogenous Krebs cycle intermediates seemed advisable for a better understanding their relationship with acid secretion. At pH 7.4, citrate, oxoglutarate, fumarate, and malate had no significant effect on oxygen uptake (QO2) nor on acid secretion (QH+) by toad gastric mucosa; succinate increased QO2 slightly and had no effect on QH+; but at pH 5.0, oxoglutarate and succinate increased QO2 by 18 and 21%, respectively. 14CO2 evolved by gastric mucosa incubated with [14C]oxoglutarate, succinate, malate, or citrate was 155, 92, 128, and 353%, respectively, greater at pH 5. Citrate, oxoglutarate, succinate, fumarate, and malate increased QH+ by theophylline-stimulated mucosa at pH 5.0 by 25, 39, 35, 17 and 28%, respectively. Oxoglutarate-dependent respiration was shown to correlate with oxoglutarate oxidation. Malonate and arsenite inhibited QO2 and QH+; malonate inhibition was reversed by washout or by succinate. Arsenite was reversed by washout and accelerated by addition of lipoate immediately after washout. The results suggest that the Krebs cycle has concomitant roles in the regulation of QH+ and oxidative metabolism in the toad gastric mucosa.


Role of pancreatic L-asparagine synthetase in homeostasis of L-asparagine. L-Asparagine synthetase from mouse pancreas was found to be associated principally with the exocrine pancreas and to be dependent on the age of the animal, but not on gender, diet, or the presence of tumor under the conditions examined. The function of the pancreatic enzyme appears to be to supply L-asparagine for the synthesis of pancreatic proteins. This function is suggested by the high specific activity of L-asparagine in pancreatic proteins after intravenous treatment of BDF1 mice with L-[U-14C]asparatate. The pancreas is also able to function as a storage depot for L-asparagine under conditions in which the concentration of the amino acid in the blood is in excess. Unlike the liver, the pancreas is unable to add L-asparagine to the circulation when the concentration of the amide is below normal limits.


Humoral regulation of vascular resistance after 30 days of pulmonary artery constriction. In an earlier study of guinea pigs with constriction of the pulmonary artery (PA) for 30 days, hindquarters' vascular resistance was maintained primarily by humoral mechanisms. In the present study, we investigated the contribution of circulating catecholamines, angiotensin II, and other constrictor stimuli to hindquarters' vascular resistance by observing vasodilator responses to specific competitive antagonists. Pressure-flow curves indicated vascular resistances in isolated, perfused, sympathectomized hindquarters of anesthetized guinea pigs. Phentolamine produced significantly greater (P less than 0.05) vasodilatation in animals with constriction of pulmonary artery than in sham animals [Sar1-Ala8]angiotensin II produced no vasodilation in either group. After alpha-adrenergic blockade, papaverine produced similar vasodilatation and similar final perfusion pressures in both groups. It appears that circulating catecholamines and augmented vasoconstrictor responsiveness to norepinephrine are totally responsible for the increased humoral regulation of vascular resistance in this experimental model of right ventricular hypertrophy.


Implications of increased dosage of neuroleptic medications during psychotherapy. Unrecognized emotional reactions on the part of the psychiatric trainee may result in the inappropriate use of medications. To illustrate the possibility that increases in medication dosages may be related to the psychiatric clinician's lack of control, the authors present three clinical examples and discuss the concept of countertransference. A model of supervision is described in which the supervisor, trainee, and patient meet to correct these therapeutic distortions and reduce the amount of medication required.


[Theories and models of the biology of aging]. Two main theories of aging were discussed: program theory, error theory. The importance of repair mechanisms is disclosed. 4 models (Lag-phase, proliferative capacity, physical properties of collagen, latency period) display typical phenomenons of the biology of aging.


[Theories of longevity (author's transl)]. Any modern theory of longevity has to take into account the multifactorial combined effect of biological-medical, social and psychological factors and of factors pertaining to molecular biology, each with their different weighting. For this reason research into greater-than-average life expectancy and longevity is only possible on an interdisciplinary basis. Many theories of longevity despite convincing arguments also have their weak points. Critical analysis of the theories available to date reveals that longevity rests on an optimal combination of two major factors: 1. on a genetic predisposition in people with longevity in the family--this is the case in most instances. 2. on additional exogenous factors of a social, psychological, ecological and medical kind.


[Orientations and models in psychogerontology (author's transl)]. As Baltes and Willis (1977) state: theories, especially psychological theories are scarce in gerontology. When we look at the short history of psychogerontology, we can differ as the first period: the period of the biological model, which offered only a negative image of growing older. This deficit-model has been unmasked, especially by the growing consciousness of the difference between cross-sectional versus longitudinal research-data. Other models as the disengagement model have been stressed. The present development towards a life-span developmental model as the background for every period of the aging process appears as the only basis for a fruitful growth of the science of psychogerontology.


[Acid phosphatase in seminal fluid--method of estimation and diagnostic significance]. A new method for the estimation of acid phosphatase in seminal fluid based on the use of p-nitro-phenylphosphate is described as simple in practicability and appropriate for routine in clinics. The frequency distribution of acid phosphatase activity is specified with 66 samples showing a normal spermiogram. The values spread logarithmically with an average of 400 U/ml and a standard deviation ranging from 200 U/ml to 880 U/ml. Correlations between acid phosphatase content and general, cytological and biochemical spermiogram-parameters are investigated. A plain negative correlation with the pH (r = 0,4615, n = 250) and a very strong positive correlation with citrate (r = +0,9029, n = 200) turned out. The significance of these correlations is discussed. Among the biochemical parameters in spermiogram both citrate and acid phosphatase--each representing prostatic function--are equivalent in diagnostical significance.


The effects of vasectomy on viscosity, pH and volume of semen in man. The effects of vasectomy on seminal viscosity, volume and pH have been investigated in freshly emitted semen of 21 healthy men before operation and three months later. Viscosity and the pH range were decreased significantly, but the decrease of the seminal volume was not significant. Reasons of changes have been discussed.


Evidence for the prostatic origin of gamma-glutamyltranspeptidase activity in human semen. Gamma-glutamyltranspeptidase activity and fructose concentration have been measured in 100 semen samples, in 7 split ejaculates and in the seminal fluid of a patient with congenital absence of ductus deferens and seminal vesicles. Evidence is presented that the prostate is the major source of gamma-glutamyltranspeptidase in human semen.


Sputum counterimmunoelectrophoresis in the diagnosis of pneumococcal pneumonia. Fifty-six patients with pneumonia were grouped according to degree of clinical certainty that the etiologic agent was Streptococcus pneumoniae. Of 14 patients with definite or probable pneumococcal pneumonia, 12 had pneumococcal antigens detected in sputum by counterimmunoelectrophoresis (CIE), 13 had a positive sputum culture, and 12 had a Gram-stained smear of sputum suggestive of the diagnosis. Of 9 patients with definite nonpneumococcal pneumonia, none had pneumococcal antigens detected by CIE, but one had pneumococci isolated from sputum culture, and one had a Gram stain of sputum suggestive of pneumococci. Of 34 control patients without pneumonia, five had a positive CIE, 11 had a positive culture, and 15 had a positive Gram stain. When used to differentiate pneumococcal from other types of pneumonia, CIE of sputum appears to be a sensitive and specific test. Among patients without pneumonia, however, CIE lacks specificity. Additionally, sputum Gram stain may correlate as well as CIE with pneumococcal pneumonia, but further substantiation of this observation is necessary.


Airway sensitivity to slow-reacting substance of anaphylaxis, histamine, and antigen in Ascaris sensitive monkeys. The effects of Ascaris suum antigen, histamine, and slow-reacting substance of anaphylaxis (SRS-A) on the respiratory system were compared in 3 anesthetized rhesus monkeys. The agents were administered by instillation into the trachea, and the animals were studied in a volume displacement body plethysmograph. Two of the animals showed skin and bronchial sensitivity to Ascaris suum antigen and responded to it with increased pulmonary resistance and decreased dynamic compliance. A similar response was seen in all 3 animals after instillation of histamine, but SRS-A at 2 concentrations produced a predominant effect of decreased dynamic compliance with lesser alterations in pulmonary resistance. The effects of SRS-A were slow in onset and prolonged, as compared to the abrupt and short-lived effects of Ascaris suum antigen and histamine. The predominant effect of SRS-A on dynamic compliance suggests a more peripheral site of action of this mediator. In 5 monkeys allergic to Ascaris, no SRS-A could be detected in the blood at one and 5 min after antigen challenge, using the bioassay techniques.


Veno-occlusive disease of the liver after allogeneic bone marrow transplantation: possible association with graft-versus-host disease. Acute veno-occlusive disease of the liver developed in seven of 29 patients undergoing bone marrow transplantation for treatment of leukemia, aplastic anemia, or disseminated carcinomatosis. All seven died despite successful marrow engraftment. Hepatic failure was the principal cause of death in four and contributory in three. The veno-occlusive disease did not relate to the nature of the pretransplant immunosuppressive regimen, since it occurred in patients receiving irradiation alone, chemotherapy alone, or both. Twenty-two of the patients were autopsied. Among these, the lesion was found in seven of 11 in whom a graft-versus-host reaction developed but in none of the 11 without such a reaction who had received similar pretransplant immunosuppression (P less than 0.025). Hence, acute veno-occlusive disease of the liver appears to be a complication of allogeneic bone marrow transplantation related to the development of a graft-versus-host reaction.


Advances in the neuropharmacology of Parkinsonism. Advances through basic research have elucidated the disturbances of neurotransmitter function in Parkinson's Dopamine has replaced acetylcholine and norepinephrine as the most studied neurotransmitter, with both conceptual and practical developments, exemplified by the hypothesis of cyclic adenosine monophosphate as a "second messenger," and new therapeutic agents. We now have rationally designed in-vitro and in-vivo tests for the evaluation of dopaminergic compounds instead of entirely empiric screening procedures. We are starting to identify different categories of dopaminergic receptors and to manipulate them selectively, with gains in understanding the physiologic input to the striatum. Crucial questions remain, including how dopamine modulates striatal output and what causes the parkinsonian degeneration of the nigrostriatal pathway. Developing knowledge on synaptic physiology and pharmacology may lead to better therapy.


Response of patients with Hodgkin's disease to pneumococcal vaccine. Postsplenectomy, 41 patients previously treated for Hodgkin's disease were given pneumococcal vaccine, and type-specific antibody levels were measured before and after immunization. Postimmunization antibody levels in patients with Hodgkin's disease were significantly lower than those in normal control subjects for 10 of the 12 serotypes measured. Mean postimmunization antibody level for patients (587 +/- 427 ng of antibody nitrogen/mL) was much lower than that for control subjects (1787 +/- 694). Antibody levels tended to increase with time from therapy for Hodgkin's disease, and several patients who had not received therapy for more than 3 years had normal responses to immunization. Despite vaccination, one patient developed pneumococcal meningitis and another, pneumococcal bacteremia. Both infected patients had low postimmunization mean antibody levels (282 and 137 ng/mL, respectively). Postsplenectomy sepsis in patients with Hodgkin's disease is related to a humoral immune deficiency probably induced by radiation and chemotherapy, and this immune deficiency persists for several years.


[Management in pollinosis and false pollinosis]. Typical cases of pollen allergen (hayfever, allergic asthma), together with isolated non-respiratory "equivalent" manifestations (urticaria, eye conditions, headache, etc.), are easy to detect on the basis of skin tests and the clinical history. Such manifestations may also occur in "false pollen allergy", related in most instances by atmospheric moulds (Dematiaceae), sometimes by house dust or dermatophytes (Candida Albicans, Trichophyton sp), by food or by a bacterial infection or allergy. A combination of pollen allergy and false pollen allergy is common. In cases of false pollen allergy the proportion of negative skin reactions would appear to worsen with the repeated use of prolonged action corticosteroid injections, given on a preventive basis. Similarly, these disorders, initially seasonal, change to more chronic manifestations throughout the year. Desensitization with aqueous extracts of allergens ensured the most complete protection against the causes of pollen allergy and false pollen allergy. Allergen extracts percipitated with alun (semi-retard extracts), more effective than tyrosine adsorbates (Pollinex) have the advantage of offering more rapid treatment without the risk of dangerous reactions. The best therapeutic results have obtained over the course of the last ten years, by the authors, combining on each occasion a semi-retard allergen with an aqueous allergen, thereby acquiring the benefit of the adjuvant effect of the first, in a course of ten to fifteen injections per year. Non specific therapy (antihistamines, cromoglycate, theophylline, etc.) retains all of its symptomatic indications. Oral corticosteroid therapy is better metabolized in the organism and has less of a disturbing effect on the circadian rhythm of cortisol, and is hence to be preferred to injections of delyaed action corticosteroid suspensions.


No barbiturate protection in a dog model of complete cerebral ischemia. Complete global ischemia was produced in 39 dogs by temporary ligation of the aorta. Prior to the ischemic episode, pentobarbital (30 to 45 mg per kilogram of body weight) was administered to 19 of these dogs. The neurological effects of cerebral ischemia episodes lasting 8, 9, or 10 minutes were compared in dogs treated with pentobarbital and those not treated. At 48 hours following the ischemic episode most of the dogs made ischemic for 8 minutes were normal, whereas most animals made ischemic for 10 minutes were dead or comatose. The 9-minute ischemic period resulted in a relatively even distribution of normal and damaged dogs. There were no differences between treated and untreated dogs. Cerebral blood flow, cerebral metabolic rate for oxygen, and various cerebral metabolites were measured in dogs surviving 48 hours. Again, there were no differences between treated and undertreated dogs. We conclude that barbiturates provide no protection in this model of complete global ischemia. This conclusion supports the hypothesis that the likely mechanism of barbiturate protection in models of incomplete ischemia or hypoxia is based on cerebral metabolic depression; such a mechanism would not be expected to be effective in complete global ischemia.


[Effect of the nutrient medium components on the formation of growth inhibition zones of the test microbe in determining the biological activity of mycoheptin]. The effect of the nutrient medium components on the diffusion properties of mycoheptin and the growth of Candida utilis as the test-microbe was studied. It was found that the content of various amounts of sodium and potassium chlorides, disubstituted sodium phosphate, glucose, yeast extract, peptone, agar-agar and the value of pH in the medium had a significant effect on the size of the inhibition growth zones of the test-culture, clearance of their margin and the angle of the dose-response curve. The nutrient medium composition considered to be optimal for determination of the mychoheptin activity is proposed.


Observations of human fetal otoconial membranes. Intact otoconial membranes from 31 human fetuses ranging in gestational age from 14 to 36 weeks were studied. At all stages of development specimens from different individuals showed marked variations in overall shape. During the course of the second and third trimesters, both saccular and utricular otoconial membranes were found to increase three to fourfold in surface area and more than twofold in weight. Near the end of gestation the fetal specimens were about equal in area and weight to otoconial membranes from children up to 13 years of age. However, the crystal layers of the fetal membranes has less prominently developed surface contours than usually observed in children and adults, indicating that maturational changes continue after the time of birth.


[Action of levorin on amino acid transport in Candida albicans]. It was shown that suppression by levorin of the leucine transport into the cells of C. albicans was due to replacement of intracellular K+ by Na+ induced by the antibiotic. The alanine transport was suppressed by levorin irrespective of the ratio of the monovalent cations concentration in the medium and inside the cell. The levorin effect on the protone escape from the cells was negligible and probably played no significant role in the mechanism of the amino acid transport suppression by the antibiotic.


Purification and some properties of two extracellular proteolytic enzymes produced by Vibrio SA1. The purification and characterisation of an extracellular endo and amino-peptidase of the marine Vibrio SA1 is described. The endopeptidase was purified by ammonium sulphate precipitation, gel filtration and affinity chromatography. It had a molecular weight of approximately 31,000, a pH optimum at 7.8 and a temperature optimum at 50 C. The enzyme was rapidly inactivated at 65 C. The aminopeptidase was purified by ammonium sulphate precipitation, gel filtration and preparative polyacrylamide gel electrophoresis. This enzyme had a molecular weight of approximately 21,000, a pH optimum at 8.6 and a temperature optimum at 60 C. Both proteases were inactivated by EDTA while reactivation occurred by Ca2+, Zn2+ and Mg2+ ions. The endopeptidase hydrolysed several peptide bonds in the oxidized B-chain of insulin, particularly those involving amino groups of hydrophobic amino acid residues with bulky side chains. It was unable to hydrolyse synthetic dipeptides, but a number of tripeptides were hydrolysed at a low rate. The aminopeptidase hydrolysed leucinamide and di- and tripeptides containing hydrophobic bulky amino acids as the N-terminal residue. It was concluded that the endopeptidase and the aminopeptidase of Vibrio SA1 possess complementary specificities.


[Effects of prolactin on chloremia and HCO3 dependant ATPase activities in kidney and gill of grey mullet, chelon Labrosus, during fresh water adaptation (author's transl)]. Only in SW fish, Prolactin (PRL) treatment increased natremia and especially chloremia. In gill, the decreases of Mg++ ATPase and SCN-sensitive, HCO3-ATPase observed in control fish after transfert from SW to FW, were more marqued in FW 8 days PRL treated fish. Renal enzyme activities were not affected by PRL treatment. If PRL treatment acts effectively on branchial ionic extrusion mechanisms, the connection between HCO3-ATPase anc Cl--transport remains to be elucidated. These results can be explained with reference to existence of two chloride-cell types.


Critical evaluation of hypertonic and hypotonic solutions to resuscitate severely burned children: a prospective study. Children with thermal burns covering 30% or more of the body surface area were alternately resuscitated with either hypertonic lactated saline (HLS) or lactated Ringer's solution (LRS). Parameters sequentially measured and calculated included: 1) serum and urine electrolyte concentrations, 2) serum and urine osmolalities, 3) arterial blood gases, 4) total and fractional serum proteins, 5) blood urea nitrogen, complete blood count and blood sugar concentration, 6) changes in body weight, 7) sodium, potassium and water balance. The water load received by the HLS group was significantly less through 48 hours postburn (49% at 8 hours, 44% at 24 hours and 38% at 48 hours postburn). Although the HLS group received significantly more sodium than the LRS group, there was no difference in sodium balance at 48 hours postburn. This is explained by the fact that the HLS group, at 48 hours postburn, retained significantly less of the administered sodium load (69% vs. 83%). Positive water balance was significantly greater in the LR group for the first 48 hours postburn. This study suggests that current hypotonic fluid regimens for burn resuscitation contain water in excess of that required for proper resuscitation. Severely burned children may be safely and efficiently resuscitated with conventional salt loads and one-third less than usual water loads.


Influence of hydrogen ion concentration on bile acid induced acute gastric mucosal ulcerogenesis. Aggressive treatment with H(2) receptor blocking agents and/or antacids has been advocated as effective prophylaxis against and treatment for "stress ulcer," based on the logical but infrequently tested assumption that the severity of the disease is critically determined by the concentration of intraluminal acid. The present study investigated this assumption in a model which employed topical acid, topical bile acid and mucosal ischemia to induce ulcerogenesis. With vascularized, chambered ex vivo wedges of canine proximal gastric wall, groups of animals were studied during three sequential periods using topical test solutions (TS) containing either 0 mM, 100 mM or 160 mM HCI. During period 1, mucosae were exposed to TS alone; during period 2, either to TS containing 1 mM sodium taurocholate (TC) or to TS and concomitant vasopressin infusion (VP); and during period 3, to TS + TC + VP. Parameters evaluated included net H(+) flux ( big up tri, openH(+)), aminopyrine clearance (AC), a measure of mucosal blood flow, net TC flux ( big up tri, openTC) and the lesion index, graded 0-5. The data indicate that in nonischemic mucosa exposed to constant [TC], AC was significantly increased, big up tri, openH(+) ("back-diffusion") increased as a linear function of [H(+)] and no lesions were observed. Under the same circumstances in ischemic mucosa, big up tri, openH(+) increased as linear function of [H(+)]. As a consequence, lesion severity was also a linear function of [H(+)]. big up tri, openTC was enhanced at low pH but bore no relation to the degree of mucosal damage induced. Assuming applicability of the model, these studies provide support for the use of H(2) receptor blocking agents and/or antacids to prevent or ameliorate "stress ulcer" disease.


Ultrastructural changes in the seminiferous tubule wall and intertubular blood vessels in human cryptorchidism. Biopsy material was obtained from adult men whose both testes had descended into the scrotal sac either spontaneously by use of pharmacologic agents or through surgery at age 7--16 yr, and from undescended testes obtained during orchipexy in men 8--40 yr of age. Testes appeared normal until the 10th yr, when progressive alterations were observed with the onset of puberty and through the adult age both in retained testes and cases of testes that descended through chemical or surgical methods before or after puberty. A thickening of the inner and outer acellular layers of the seminiferous tubule wall was due to an accumulation of collagen fibers and microfibrillar material. The basement membrane was also thickened and appeared as a homogeneous or a multilaminar structure. The intertubular blood vessels presented a thickening of the tunica media and a laminar accumulation of basement-membrane-like material.


Lung volume and blood oxygenation after intermittent positive pressure breathing. Functional residual capacity (FRC) was measured in 12 postoperative patients and in one preoperative patient before and after they received intermittent positive pressure breathing (IPPB) with room air for ten minutes at a peak delivered pressure of 15 cm H2O. Ten patients had a normal or low pretreatment FRC. After cessation of IPPB, the mean FRC decreased further. Arterial oxygen tensions, measured in 11 of the 13 patients, decreased in all 11 from a pretreatment mean of 67.8 +/- 4.3 mm Hg to an immediate posttreatment mean of 57.7 +/- 4.2 mm Hg. In five patients repeated arterial blood gases were measured. At 30 minutes, their arterial oxygen tensions had returned to the pre-IPPB values. This study demonstrates that the routine use of IPPB in postoperative patients accentuates preexisting hypoxia and, therefore, must be used with caution.


Relationship of muscle surface pH to noninvasive hemodynamic studies in arterial occlusive diseases. To examine the possible relationship between Doppler pressures (DP) and pulse volume amplitude (PVR) with muscle surface pH (pHm), we studied 20 patients before, during, and after arterial reconstruction. The mean pHm for the claudication, rest pain, and ischemic gangrene groups differed from a control group and from each other. The pHm varied directly with DP and PVR for the 20 patients as a whole. After reconstructive surgery, improvement in pHm seemed to precede changes in DP and PVR in six patients with combined segment disease. Although pHm correlates generally with DP and PVR, it is invasive. Therefore, pHm should not be used as a routine screening test. Whereas DP and PVR may reflect the anaerobic activity of peripheral tissue, they may be less prompt than pHm in responding to acute changes in blood flow.


Hepatic blood flow and metabolism.

Hepatic blood flow and metabolism. The relationship between liver blood flow and hepatic metabolism remains unclear. An animal model as well as a methodology that permits simultaneous assessment of both of these functions are proposed. Several fractions of inspired oxygen were used to produce arterial oxygen levels commonly seen in clinical practice; these ranged from hyperoxemia to established hypoxemia. Over this range there were no considerable changes in transhepatic blood flow, but there were considerable changes in hepatic metabolism as shown by measurements of the hepatic parenchymal pH, transhepatic oxygen consumption, and lactic acid use. Of these, the parenchymal pH seems to be the most sensitive indicator of metabolic events.


[Effects of barbexaclone in Lennox-Gastaut syndrome]. The Lennox-Gastaut syndrome has been a source of interest for many workers both from a clinical and electroencephalographic view point. Treatment has always posed problems. Without suggesting an ideal medication for this syndrome, the authors have obtained good results with barbexaclone. Taking into consideration the convulsive manifestations, psychic changes and electroencephalographic details as parameters the therapeutic efficacy of this drug was studied in seven cases.


Human tear buffering capacity.

Human tear buffering capacity. With the use of a closed chamber microelectrode system, we measured the relative buffering capacities of 490 human tear samples from young healthy adults. The buffering capacities of the 457 waking-hour samples did show small but regular oscillations that were similar to those previously reported for blood and tear pH, but only rarely did the buffering capacity of one sample approach double that of another. The buffering capacities of 33 tear samples, associated with periods of prolonged eye closure (sleep), were not significantly different (P less than 0.5) from those of the open eye.


A metallographic evaluation of the stainless steel-silver solder joint. A technique has been developed and described for the examination of the interface between dissimilar metals, utilizing electrolytic etching and gold electro-deposition procedures. This procedure permitted etching of both the constituents of the silver solder-stainless steel interface without differential leveling. The grain boundaries at the surface of the stainless steel interface were accentuated by the chemical action of the flux during the joining procedure and the notched grain boundaries influenced the nucleation of the silver solder. No evidence of alloying was found within the resolution of the instruments used.


alpha-Glucosidase activity in the reproductive tract of the ewe. alpha-Glucosidase activity has been estimated in the tissues and rinsings of the reproductive tract of the ewe. There were peaks of activity in the oviducal mucosa at pH 4.0 and 5.7. In the endometrium, caruncles and cervical mucosa and pH optimum occurred from pH 4.0 to pH 5.7. A sharp peak in the activity in the vaginal mucosa occurred at pH 5.7. The only tissue in which changes in enzyme activity were consistently related to one endocrinological state of the ewe was the cervical mucosa. Cervical alpha-glucosidase activity was greater at oestrus than during the rest of the oestrous cycle, declined during early pregnancy, and increased in ovariectomized ewes following the injection of oestradiol-17 beta.


The binding of rat liver cell multiplication-stimulating activity (MSA) to human placenta and serum proteins. Multiplication-stimulation activity (MSA) from the medium of BRL-3A rat liver cells in culture binds to cell membrane and cytosol receptors from human placenta and to serum proteins. The binding of MSA to placental cell membranes is dependent on time, temperature, pH and divalent ion concentration. MSA bound to placental cytosol receptor and serum is not displaced by insulin, whereas that bound to placental cell membranes is displaced by insulin and insulin-like peptides. The affinity of the three receptors for MSA is similar [approximately 10(8) M(-1)]. An assay using 125I-MSA and placental membrane receptor detects somatomedin-like receoptor activity (SmLRA) in unextracted sera from man and animals. A binding protein in serum that competes for 125I-MSA with receptor could not be completely separated from SmLRA by heating, acidification, charcoal treatment and gel chromatography of the serum. The relative activities of SmLRA and serum binding protein remained constant in three disorders of human growth (acromegaly, growth hormone deficiency and Laron's dwarfism) in which values of SmLRA varied widely. However, the binding protein is only partly responsible for the apparent SmLRA of unextracted serum. It is concluded that MSA is a suitable radioligand for the investigation of somatomedin disorders in man either by receptor assays or by studies of tissue receptors.


Cardiorespiratory assessment of decongestant-antihistamine effects on altitude, +Gz, and fatigue tolerances. Decongestants and antihistamines are known to produce effects capable of adversely modifying physiological function and psychomotor task performance. Because of relevance to safe pilot performance, the effects of single doses of two decongestant-antihistamine preparations (Compound A and Compound B), or a placebo on cardiorespiratory responses to two equally spaced +2 Gz tests during separate 2-h exposures at 388 m (1,274 ft MSL) ground level (GL) and 3,810 m (12,500 ft) chamber altitude were assessed. Post-altitude fatigue was assessed by cardiorespiratory responses to submaximal bicycle ergometry. Compound A and Compound B appeared to exert no significant detrimental effects on short-duration post-altitude ergometric fatigue-ability. With two exceptions, all combinations of medication, altitude, and +Gz were well tolerated. Two subjects were clearly incapacitated during the first +2 Gz test under Compound A at 3,810 m (12,500 ft) altitude. It is felt that the +Gz-intolerance resulted mainly from an adverse interactive effect of Compound A and altitude on vasomotor and/or chronotropic mechanisms.


Effects of altitude and two decongestant-antihistamine preparations on physiological functions and performance. Fourteen men were studied to determine the combined effects of two altitudes--388 and 3,810 m or 1,274 and 12,500 ft--and three preparations--lactose placebo, Compound A (Actified, and Compound B (Dristan). Subjects reported least attentiveness with A and greatest with placebo. Fatigue increased significantly with time while energy, interest, and attentiveness decreased. The Multiple Task Performance Battery (MTPB) showed no effects of altitude, drugs, or time on overall performance; however, performance declined with time in several tasks, while problem solving improved. Subjects enjoyed the problem-solving tasks and may have given them preference as levels of interest declined. Though the MTPB overall composite scores did not change significantly, physiological parameters and subjective evaluations indicate that type of compound and time after ingestion are important. Declines in energy and attentiveness 2.5 h after ingestion could result in neglect of important--although routine--tasks. Hypoxia might enhance this effect and consequences might be worse in subjects whose medical conditions require these drugs.


Prevention and treatment of space sickness in shuttle-orbiter missions. Today it is impossible accurately to predict susceptibility to space sickness of crew members making their first transition into orbit, for want of a ground-based validated model of free fall. Even assuming that space sickness is simply a specific designation for motion sickness that may be experienced in orbital flight (and here agreement is not general), preventive therapy poses difficult problems because, for a priori reasons, either all crew members or none should receive treatment. If all receive preventive therapy, everyone should execute head movements in a programmed manner to ensure rapid adaptation to the environment; at least a large minority will not benefit but rather will experience whatever sideeffects inevitably accompany administration of a drug. If none receive preventive therapy prelaunch, at least a large minority will pose two problems--treatment for acute motion sickness and rapid acquisition of adaptation. Trade-offs will involve the identification of long-acting antimotion sickness drugs for use prelaunch that will be efficacious for at least 90% of those going aloft for the first time and the effectiveness of combining rapid adaptation with treatment of motion sickness. The following report describes recent experiments dealing with these problems.


Evaluation of a life support module used for air transport of critically ill infants. To accomplish the safe transport of ill newborns, various infant transport systems have been developed. One such unit, produced by Airborne Life Support Systems, has been tested by the authors. The parameters used to evaluate the system were: (1) temperature stability at 2 degrees C and -28 degrees C ambient; (2) rate of internal temperature fall-off when all power to the unit was interrupted; (3) degree of CO2 accumulation, and (4) internal sound levels. Without heat shield, temperature decrease at 2 degrees C ambient was 12 degrees C/h; with head shield, 2 degrees C/h for the first hour and 0.9 degrees C in the second hour. At -28 degrees C ambient, temperature decrease was 6.1 and 2.2 degrees C/h for the first and second hour, respectively. The rate of temperature fall-off was 15.6 degrees C in 45 min. Average CO2 accumulation was 0.24% after 2 h. Sound level for heater and fan was 16.5 dB. An additional 1 dB of noise was contributed to the system when air and oxygen were turned on.


Biochemical characterization of a red cell UMP kinase variant found in the Warao indians of Venezuela. UMPK 3 is a rare variant of the polymorphic enzyme of human red cells, uridine monophosphate kinase. This homozygote phenotype was detected among the Warao Indians of Venezuela. The UMPK 1 and UMPK 3 enzymes were partially purified following the method described by Tend et al. (1976). The biochemical and kinetic parameters of both variants were studied in crude hemolysates and in partially purified enzymes. A comparison was made with the results previously reported by Teng for UMPK 1 and UMPK 2, and it was concluded that UMPK 3 seems to resemble the other two allelic gene products in Km values for UMP, CMP, and ATP but differs from them in electrophoretic mobility, pH optimum, and thermal stability.


A detailed investigation of the properties of lactate dehydrogenase  in which the 'Essential' cysteine-165 is modified by thioalkylation. The reaction of pig heart lactate dehydrogenase with methyl methanethiosulphonate resulted in the modification of one thiol group per protomer, and this was located at cysteine-165 in the enzyme sequence. On reduction, both the thiomethylation of cysteine-165 and any changes in kinetic properties of the enzyme were completely reversed. Cysteine-165 has been considered essential for catalytic activity; however, cysteine-165-thiomethylated dehydrogenase possessed full catalytic activity, although the affinity of the enzyme for carbonyl-or hydroxy-containing substrates was markedly decreased. The nicotinamide nucleotide-binding capacity was unaffected, as judged by the formation of fluorescent complexes with NADH. The enzyme-mediated activation of NAD+, as judged by sulphite addition, was unaffected in thiomethylated lactate dehydrogenase. However, the affinity of oxamate for the enzyme--NADH complex was decreased by 100-fold and it was calculated that this constituted a net increase of 10.4 kJ/mol in the activation energy for binding. Thiomethylated lactate dehydrogenase was able to form an abortive adduct between NAD+ and fluoropyruvate. However, the equilibrium constant for adduct formation between pyruvate and NAD+ was too low to demonstrate this complex at reasonable pyruvate concentrations. A conformational change in the protein structure on selective thiomethylation was revealed by the decreased thermostability of the modified enzyme. The alteration of lactate dehydrogenase catalytic properties on modification depended on the bulk of the reagent used, since thioethylation resulted in an increase in Km for pyruvate (13.5 +/- 3.5 mm) and an 85% decrease in maximum catalytic activity. The implications of all these findings for the catalytic mechanism of lactate dehydrogenase are discussed.


Inhibitory effects of histidine and their reversal. The roles of pyruvate carboxylase and N10-formyltetrahydrofolate dehydrogenase. 1. N10-Formyltetrahydrofolate dehydrogenase was purified to homogeneity from rat liver with a specific activity of 0.7--0.8 unit/mg at 25 degrees C. The enzyme is a tetramer (Mw = 413,000) composed of four similar, if not identical, substrate addition and give the Km values as 4.5 micron [(-)-N10-formyltetrahydrofolate] and 0.92 micron (NADP+) at pH 7.0. Tetrahydrofolate acts as a potent product inhibitor [Ki = 7 micron for the (-)-isomer] which is competitive with respect to N10-formyltetrahydrofolate and non-competitive with respect to NADP+. 3. Product inhibition by NADPH could not be demonstrated. This coenzyme activates N10-formyltetrahydrofolate dehydrogenase when added at concentrations, and in a ratio with NADP+, consistent with those present in rat liver in vivo. No effect of methionine, ethionine or their S-adenosyl derivatives could be demonstrated on the activity of the enzyme. 4. Hydrolysis of N10-formyltetrahydrofolate is catalysed by rat liver N10-formyltetrahydrofolate dehydrogenase at 21% of the rate of CO2 formation based on comparison of apparent Vmax. values. The Km for (-)-N10-folate is a non-competitive inhibitor of this reaction with respect to N10-formyltetrahydrofolate, with a mean Ki of 21.5 micron for the (-)-isomer. NAD+ increases the maximal rate of N10-formyltetrahydrofolate hydrolysis without affecting the Km for this substrate and decreases inhibition by tetrahydrofolate. The activator constant for NAD+ is obtained as 0.35 mM. 5. Formiminoglutamate, a product of liver histidine metabolism which accumulates in conditions of excess histidine load, is a potent inhibitor of rat liver pyruvate carboxylase, with 50% inhibition being observed at a concentration of 2.8 mM, but has no detectable effect on the activity of rat liver cytosol phosphoenolpyruvate carboxykinase measured in the direction of oxaloacetate synthesis. We propose that the observed inhibition of pyruvate carboxylase by formiminoglutamate may account in part for the toxic effect of excess histidine.