Effect of adrenalectomy on cadmium- and turpentine-induced hepatic synthesis of metallothionein and α2-macrofetoprotein in the rat

Recent reports have strongly implicated glucocorticoids in the induction of hepatic metallothionein synthesis and hypozincemia which occurs in certain pathophysiologic conditions. Studies were performed in rats to determine the effect of adrenalectomy and glucocorticoid treatment on the hepatic accumulation of metallothionein subsequent to the administration of cadmium and turpentine, two diverse substances known to induce hypozincemia and hepatic synthesis of metallothionein as well as ₂-macrofetoprotein in intact rats. By 24 h, both substances induced significant hypozincemia, hepatic metallothionein accumulation, and a severe tissue inflammatory response in adrenalectomized rats. Adrenalectomy only prevented the increase in plasma ₂-macrofetoprotein concentration. Results indicate that hepatic synthesis of ₂-macrofetoprotein, but not metallothionein, is mediated by adrenal hormones. Thus, glucocorticoids do not play a vital role in hepatic metallothionein accumulation or hypozincemia induced by inflammatory stress, as previously postulated.In conducting the research described in this report, the investigators adhered to the Guide for the Care and Use of Laboratory Animals, as promulgated by the Committee on Care and Use of Laboratory Animals of the Institute of Laboratory Animal Resources, National Research Council. The facilities are fully accredited by the American Association for Accreditation of Laboratory Animal Care.The views of the authors do not purport to reflect the positions of the Department of the Army or the Department of Defense (Para. 4-3, AR 360-5).     

Effect of inflammatory and noninflammatory stress on plasma ketone bodies and free fatty acids and on glucagon and insulin in peripheral and portal blood

Inflammatory stress as characterized by infection withStreptococcus pneumoniae, administration of endotoxin, or the induction of a turpentine abscess is characterized by the inhibition of the ketosis associated with fasting and a decline in the level of free fatty acids in the plasma. Moreover, rats subjected to these inflammatory stresses demonstrate a significant rise in peripheral and portal insulin and glucagon. Rats subjected to noninflammatory stresses, screen-restraint, or noninvasive femoral fracture did not demonstrate the inhibition of ketosis but did show a decrease in plasma free fatty acids. The noninflammatory stresses did not show an abnormal elevation of plasma or portal insulin or glucagon.The views of the authors do not purport to reflect the positions of the Department of the Army or the Department of Defense.In conducting the research described in this report, the investigators adhered to the Guide for the Care and Use of Laboratory Animals, as promulgated by the Committee on the Revision of the Guide for Laboratory Animal Facilities and Care of the Institute of Laboratory Animal Resources, National Research Council. The facilities are fully accredited by the American Association for Accreditation of Laboratory Animal Care.     

Vascular clearance of Venezuelan equine encephalomyelitis viruses as a correlate to virulence for rhesus monkeys

Summary The epizootic Trinidad donkey strain of Venezuelan equine encephalomyelitis virus (VEE) was cleared slowly from the circulation of rhesus monkeys following intravenous inoculation, while the live, attenuated vaccine strain, TC-83, was cleared rapidly. The efficient clearance of TC-83 vaccine may be a factor in the lower viremia and benign course of TC-83 virus infection in rhesus monkeys.With 1 FigureIn conducting the research described in this report, the investigators adhered to the Guide for the Care and Use of Laboratory Animals, as promulgated by the Committee on Revision of the Guide for Laboratory Animal Facilities and Care of the Institute of Laboratory Animal Resources, National Research Council. The facilities are fully accredited by the American Association of Accreditation of Laboratory Animal Care.     

Virulence alterations of Tacaribe virus infection in adult mice: Lethal model for encephalitis

Summary Selection of populations of Tacaribe virus strain 11573 lethal for mice was carried out by serial intracerebral passage of the virus in adult mice. Viral populations have been characterized by determination of virulence for suckling, weanling, and adult mice, and by histopathologic changes observed in brains of adult mice after intracerebral inoculation. Some of the virus preparations produced 80 to 90 per cent mortality after two or three intracerebral passages in adult mice and maintained this virulence for 1 to 3 passages, after which the virulence rapidly declined with subsequent passages. Clinical signs of infection in adult mice were manifested by a rough hair-coat, ventriflexed posture, diminished activity, increased excitability, flaccid hind-limb extension with progressive paralysis and death. Histologic examination revealed meningoencephalitis.With 2 FiguresIn conducting the research described in this report, the investigators adhered to the Guide for the Care and Use of Laboratory Animals, as promulgated by the Committee on the Revision of the Guide for Laboratory Animal Facilities and Care of the Institute of Laboratory Animal Resources, National Research Council. The facilities are fully accredited by the American Association for Accreditation of Laboratory Animal Care.The views of the authors do not purport to reflect the positions of the Department of the Army or the Department of Defense.     

The gerbil,Meriones unguiculatus,a model for Rift Valley fever viral encephalitis

Summary The gerbil,Meriones unguiculatus, was investigated as a model for the encephalitic form of Rift Valley fever. Resistance to necrotizing encephalitis was age-dependent with 100% mortality at 3 weeks, decreasing to approximately 20% by 10 weeks of age in outbred gerbils inoculated subcutaneously. Fatal encephalitis in the 10-week-old adults was dose-independent [1.0–7.0 log₁₀ plaque forming units (PFU), subcutaneously]. Viral replication and histological lesions were followed serially throughout the course of the infection in young (4 week) and adult (10 week) gerbils. Viral replication was evident in the brain tissue of young gerbils from day 4 (3.0 log₁₀ PFU/g) through day 7 (6.0 log₁₀ PFU/g), the last day the young gerbils survived. Virus was only detected in the brain tissue of a single adult gerbil (day 7, 4.0 log₁₀ PFU/g) of 26 studied in the sequential survey. In contrast, two moribund adult gerbils had approximately 7.0 log₁₀ PFU/g of virus in the brain tissue on days 8 and 11. When young and adult gerbils were inoculated with a low dose (50 PFU) of virus intracranially, there were no detectable differences in the course of infection with all animals succumbing to fatal necrotizing encephalitis aproximately 7 days postinoculation. The young gerbil becomes the first animal model in which uniformly fatal RVFV-induced encephalitis is produced without significant extraneural lesions.In conducting the research described in this report, the investigators adhered to the Guide for Care and Use of Laboratory Animals, as prepared by the Committee on Care and Use of Laboratory Animals of the Institute of Laboratory Animal Resources Commission on Life Sciences-National Research Council. The facilities are fully accredited by the American Association for Accreditation of Laboratory Animal Care.The views of the author(s) do not purport to reflect the positions of the Department of the Army or the Department of Defence (Paragraph 4-3, AR 360-5).     

Effect of adrenergic receptor blocking agents on mitotic activity of the regenerating liver

The -adrenergic blocking drug phentolamine was injected into male rats 1 h before resection of 70% of the liver and again 24 h after the operation. Phentolamine inhibited mitotic activity of the regenerating liver. Two injections of propranolol, a -adrenergic blocking drug, at the same times caused an increase in mitotic activity. It was concluded that adrenalin, which excites -adrenergic receptors, may inhibit regeneration. By its action through -adrenergic receptors, however, adrenalin stimulates this process.Department of Physiology of Animals, N. G. Chernyshevskii Saratov University. Central Scientific-Research Laboratory, Saratov Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR A. P. Avtsyn.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 82, No. 11, pp. 1373–1374, November, 1976.     

Development of rib-vertebrae: a new mutation in the house mouse with accessory caudal duplications

Summary The new recessive mutation rib-vertebrae (rv) causes fusions of lower ribs and malformations of vertebrae, which results from disturbed somite arrangement. In addition, duplications of the caudal neural tube and sometimes unilateral suppression of kidney formation can be observed. The new mutation is compared with the six already known mutations in mice with Wirbel-Rippen-Syndrome and with a similar syndrome in man. From the various effects of the rv-gene observed, it is suggested that the gene causes abnormal inner and outer surface formation, producing manifold secondary effects.This work was supported by NIH Research Grant RR 01183The Jackson Laboratory is fully accredited by the American Association for Accreditation of Laboratory Animal Care     

Modulation of phospholipase A2 lytic activity by actin and myosin

Prostacyclin (PGI₂) production is closely coupled with endothelial cell shape and F-actin distribution in vitro. These findings may implicate cytoskeletal constituents in a mechanism regulating eicosanoid metabolism. To determine the potential for such a regulatory mechanism, cytoskeletal protein effects on the ratelimiting eicosanoid cascade enzyme (phospholipase A₂; PLA₂) were studied. Membrane phospholipid degradation was indirectly determined by spectrophotometric measurement of PLA₂-induced rat red blood cell ghost (RBC-G) hemolysis. PLA₂ was incubated with actin (skeletal, smooth, or nonmuscle cell) at a nonmuscle cell concentration (100M) and then exposed to the RBC-G. Comparisons in the presence or absence of actin revealed that F-actin stimulated whereas G-actin suppressed PLA₂ lytic behavior significantly (P<0.05). When a 10: or 1001 F-actin to myosin ratio was used, the F-actin stimulatory effect was significantly (P<0.05) reduced. These findings suggest that the in vitro correlation between PGI₂ production and endothelial cell shape may be the result of PLA₂ regulation by cytoskeletal elements that impart cellular form.The investigators adhered to the Guide for Laboratory Animal Facilities and Care as promulgated by the committee on the Guide for Laboratory Animal Facilities and Care of the Institute of Laboratory Animal Resources, National Academy of Sciences, National Research Council. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.     

A spontaneous temperature sensitive mutant of Japanese encephalitis virus: Preliminary characterization

Summary A spontaneously arising temperature sensitive (ts) mutant of Japanese encephalitis virus (JEV),ts 104, was isolated from chick fibroblast (CF) cell cultures of JEV strain M1/311. Straints 104 was plaque purified and characterized to ascertain its potential as a candidate for a live vaccine. Parameters of its growth, temperature lability, immunogenicity and virulence were examined.Ts 104 has been shown to be a stablets JEV strain, multiplying as well as the parent strain in CF cultures at 35° C, but not multiplying at 39° C. It was avirulent for embryonated chicken eggs incubated at 39° C and of reduced virulence for intracerebrally (i. c.) inoculated mice as measured by LD₅₀ in weanling mice and average day of death in weanling and suckling mice. Intraperitoneal injection of adult mice with either parent orts strain resulted in similar levels of protection against challenge with either strain. The potential ofts 104 as a candidate live JEV vaccine strain is discussed.With 1 FigureDisclaimers: Supported by Naval Medical Research and Development Command, Navy Department, Research Task No. MF 51.524.009.0067. The opinions and statements contained herein are the private ones of the writer and are not to be construed as official or reflecting the views of the Navy Department or the naval service at large.The animals used in this study were handled in accordance with the provisions of Public Law 89–44 as amended by Public Law 91–579, the Animal Welfare Act of 1970 and the principles outlined in the Guide for the Care and Use of Laboratory Animals, U.S. Department of Health, Education and Welfare Publication No. (NIH) 73–23.     

Immunochemical study of human trophoblast-specific β1-globulin and its analogs in animals

Human trophoblast-specific ₁-globulin and specific pregnancy -globulins of rabbits, rats, and guinea pigs possess immunologic similarity. Similar antigenic determinants, not detectable by immunodiffusion methods, were found by preincubation of these agents with heterologous antisera.Department of Biochemistry and Problem Laboratory for Immunochemistry of Malignant and Embyronic Tissues, N. I. Pirogov Second Moscow Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR Yu. M. Lopukhin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 89, No. 3, pp. 294–295, March, 1980.     

Action of a serum protein on muscular contraction

Summary The mechanism of action of a serum protein isolated from human serum was assessed in several experimental preparations including glycerol-treated muscle fibers, rat heart papillary muscle and isolatedin vitro perfused rat heart. The action of the serum protein was studied also on canine and human heart papillary muscles which were made to respond to electrical stimulation with ultrasonication modified epinephrine. In addition the action of the protein on adenosine 5 triphosphate generated precipitation of purified human actomyosin was investigated.The serum protein enhanced and intensified the generation of ATP induced tension in glycerol-extracted muscle fibers. It intensified the developed tension (DT) and increased the rate of development of tension (dT/dt) without influencing the time peak tension (TPT) of capillary muscles from rat, canine and human hearts in response to electrical stimulation. The serum protein increased the force of contraction of the isolatedin vitro perfused rat heart, and accelerated the adenosine 5 triphosphate generated precipitation of purified human heart actomyosin.     

Effect of recombinant mouse interferon-β on acute and latent herpes simplex infection in mice

Summary The antiviral effect of recombinant mouse interferon-(rMuIFN-) on herpes simplex virus type 1 (HSV-1) in experimentally infected mice was examined at several stages of infection as a model for the treatment of human HSV infection. Recombinant MuIFN- protected mice from lethal intraperitoneal challenge with virulent HSV-1 strains. The in vitro reactivation of HSV from latently infected trigeminal ganglia was also suppressed by treatment with rMuIFN-. Thus, rMuIFN- was effective against HSV-1 during acute infection and during in vitro reactivation of latent HSV. However, rMuIFN- was not effective in preventing the establishment of latent infection, or in eliminating a previously established latent infection.     

Identification and quantitation of cortisol metabolites in rat liver homogenate and -slices

Summary Cortisol-1, 2-H³ was incubated with rat liver homogenate and/or rat liver slices in the presence of a NADPH-generating system. The following metabolites could be identified in adult male rats: -cortol, allo--cortol, 3-allo--cortol, 20-hydroxy-cortisol, 11, 17, 20, 21-tetrahydroxy-5-pregnan-3-one, 3-allotetrahydrocortisol, tetrahydrocortisol, trace amounts of allotetrahydrocortisol and two highly polar metabolites only partly identified. In female rats only tetrahydrocortisol, allotetrahydrocortisol and allodihydrocortisol could be detected in significant amounts.The radioactive metabolites mentioned above were localized and quantitated on paper chromatograms by a 4-radiochromatogram scanner. A nearly perfect correlation was found between these results so obtained and those given by liquid-scintillation counting of each metabolite after its elution from the paper.Part of this work was supported by grant n° 695 of the National Fonds voor Wetenschappelijk Geneeskundig Onderzoek.Stagiair of the Nationaal Fonds voor Wetenschappelijk Onderzoek.     

Effect of antihepatocytotoxic serum on DNA synthesis in the rat

Incorporation of thymidine-³H into parenchymatous and reticulo-endothelial cells of the liver was studied autoradiographically in adult female rats treated with small doses (0.06 g/100 g body weight per injection) of antihepatocytotoxic serum (AHTS), the -globulin isolated from it (AHTS), and the -globulin fraction of normal rabbit serum (NRS) to intact animals and to rats with liver damage caused by carbon tetrachloride (CCl₄). Following injection of AHTS and, to a lesser degree, of AHTS into intact animals the index of labeled nuclei of both the parenchymatous and the reticulo-endothelial cells was increased. When given after preliminary CCl₄ administration, AHTS stimulated reparative regeneration. The action of AHTS took place in phases: A period of increase in the index of labeled nuclei was followed by a period of decrease, and this again was followed by a fresh period of stimulation of proliferative processes.Department of Immunology and Cytotoxic Sera, A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. (Presented by Academician of the Academy of Medical Sciences of the USSR N. N. Gorev.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 86, No. 7, pp. 75–78, July, 1978.     

Aggravation of injury to liver lysosomes of rats with CCl4 hepatitis by preliminary prolonged administration of chlorpromazine

Preliminary prolonged administration of chlorpromazine (5 mg/kg for three weeks) aggravated the injury to liver lysosomes of rats with acute CCl₄ hepatitis. Similar marked changes were observed in lysosomes sedimented with heavy and light mitochondrial fractions.Central Scientific-Research Laboratory and Department of Psychiatry, Novosibirsk Medical Institute. (Presented by Academician, of the Academy of Medical Sciences of the USSR V. P. Kaznacheev.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 1, pp. 38–41, January, 1977.     

Distant intercellular electromagnetic interaction between two tissue cultures

Experimental data on distant intercellular electromagnetic interaction between two tissue cultures when one of them is exposed to factors of biological (viruses) or chemical (mercuric chloride) nature are presented; the characteristic response of the intact culture is in the form of a mirror cytopathic effect.Laboratory of Biophysics, Institute of Clinical and Experimental Medicine, Siberian Branch, Academy of Medical Sciences of the USSR, Novosibirsk. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 89, No. 3, pp. 337–339, March, 1980.     

Effects of delayed myelination by oligodendrocytes and Schwann cells on the macromolecular structure of axonal membrane in rat spinal cord

Summary The macromolecular structure of axonal membrane from dorsal funiculi of control and irradiated spinal cord of 45-day-old rats was examined with freeze-lracture electron microscopy. In control spinal cords, virtually all myelination is mediated by oligodendrocytes, and the internodal axonal membrane of these fibres displays highly asymmetrical partitioning of intramembranous particles (IMPs). The internodal P-face particle density is 2350 IMPs per m², whereas the E-face IMP density is 150 per m². In control dorsal spinal roots, myelination is mediated by Schwann cells, and the ultrastructure of the internodal axolemma of the myelinated fibres is similar to that displayed by myelinated fibres of dorsal funiculi. On the internodal P-face of Schwann cell-myelinated fibres the IMP density is 2350 per m², whereas on the E-face the density is 175 per m². Irradiation of the lumbosacral spinal cord at 3 days of age results in a glial cell-deficient region within the spinal cord such that myelination in irradiated dorsal funiculi is delayed and subsequent myelination is mediated by both oligodendrocytes and Schwann cells. By 45 days of age, dorsal funiculi of irradiated spinal cords are well populated with fibres myelinated by oligodendrocytes and Schwann cells. However, fibres myelinated by oligodendrocytes display very thin myelin sheaths whereas Schwann cell-myelinated fibres exhibit myelin sheaths with normal thicknesses. Internodal membrane of fibres myelinated by Schwann cells and oligodendrocytes exhibit similar macromolecular structure, with 2400 IMPs per m² on P-faces and 150 IMPs per m² on E-faces. Occasional large (>1.5 m diameter) axons without glial-Schwann cell ensheathment are observed. These axons display a high density of P-face particles (2000 per m²) and a moderate density (350 per m²) of E-face IMPs on their fracture faces. These results demonstrate that CNS fibres exhibit similar axonal membrane ultrastructure irrespective of whether they are myelinated by Schwann cells or oligodendrocytes, or whether myelination is delayed. Moreover, when myelination does not occur, the axolemmal E-face IMP density, which may be related to the density of voltage-sensitive sodium channels, is not reduced.     

Integrin Expression on Neutrophils in a Rabbit Model of Group B Streptococcal Meningitis

Products released by polymorphonuclear cells (PMNs) during an acute inflammatory response can result in diffuse tissue injury. Integrins are cell surface adhesion proteins that play a pivotal role in inflammation by allowing PMNs to adhere to the endothelium and migrate through the extracellular matrix. We examined the expression of ₁ and ₂ integrins on neutrophils from blood and cerebrospinal fluid (CSF) in an animal model of Group B Streptococcal meningitis. We further evaluated whether integrin expression correlates with pathophysiologic markers of central nervous system inflammation. Our data demonstrate that ₁ and ₂ integrin expression on circulating neutrophils does not significantly increase as a consequence of meningitis. In extravesated CSF neutrophils, a significant increase in expression of both ₁ and ₂ integrins is noted. Furthermore, a majority of the ₁ integrins on extravesated neutrophils have undergone affinity modulation. Using regression analysis, we demonstrated that increasing ₁ integrin expression correlates with decreasing CSF glucose concentration and serum/CSF glucose ratio. Regression analysis approached significance when CSF protein was compared to PMN ₁ integrin expression. Polymorphonuclear leukocytes ₁ integrin expression also showed a direct correlation to myeloperoxidase activity in brain tissue. ₂ expression on CSF PMNs did not correlate with these markers of inflammation/sequestration. These data demonstrate integrin expression on extravesated neutrophils markedly increases during meningitis and support a role for ₁ integrins on neutrophils in the pathophysiologic consequences of meningitis.     

DNA-Antiviral Vaccines: New Developments and Approaches—A Review

Current vaccines can be divided into live, recombinant and killed vaccines. Live vaccines are traditionally composed of attenuated viruses or bacteria, selected for their reduced pathogenicity. Recombinant vaccines, driven by a viral or bacterial vector express foreign antigens, or only recombinant proteins injected as antigen. Killed vaccines consist of inactivated whole pathogens. But all these traditional vaccines have some disadvantages: Attenuated live vaccine are able to undergo mutation and as mutated viruses or bacteria can now provoke the diseases against which the vaccine should protect the organism. A further disadvantage of live vaccines is the possibility of shedding which is a real problem especially in veterinary medicine. Clearly, there is a need for better vaccines to protect against diseases without the disadvantages associated with vaccines presently in use. Modern vaccines might be characterized as safe, no risk of reversion to pathogenicity, and they should be stable without the necessity of a cold chain. Production should be simple, standardized and inexpensive. Vaccine development has now been improved by the ability to use direct inoculations of plasmid DNA encoding viral or bacterial proteins. One of the major benefits of DNA-vaccines, variously termed DNA-, genetic- or nucleic acid-immunization, is the endogenous synthesis of the encoded protein. Therefore DNA vaccines mimic natural infection and provoke both strong humoral and cellular immune response. This review summarizes new developments and approaches of DNA vaccination and explains the construction of expression plasmids as well as possible mechanisms of immune responses.     

Zur Physiologie und Pharmakologie von Endorphinen

Zusammenfassung Die vor wenigen Jahren entdeckten Endorphine sind Peptide mit Opioid-ähnlicher Wirkung, die in verschiedenen Geweben des Organismus, vor allem im Darm und im Zentralnervensystem, synthetisiert werden. Die Entdeckung dieser Substanzgruppe war erst möglich, nachdem Opioid-spezifische Rezeptoren exakt charakterisiert werden konnten und sehr empfindliche Testmethoden für Opioide entwickelt worden waren. Die beiden zuerst entdeckten Endorphine, die Enkephaline, sind Pentapeptide, von denen das met-Enkephalin (H-Tyr-Gly-Gly-Phe-Met-OH) offenbar ein Bruchstück der ebenfalls Opioid-ähnliche Wirkung zeigenden Peptide - und -Endorphin sowie des in dieser Hinsicht unwirksamen Polypeptids -Lipotropin ist: Alle diese Peptide enthalten die Sequenz von met-Enkephalin. -Lipotropin und ACTH entstammen sehr wahrscheinlich einer gemeinsamen Vorstufe. Mindestens die (besonders gut untersuchten) Enkephaline entstehen offensichtlich im Zellkörper und werden von dort zur Nervenendigung transportiert, wo sie freigesetzt werden und vermutlich als Neuromodulatoren oder sogar Neurotransmitter fungieren.Endorphine zeigen ein ähnliches pharmakologisches Wirkungsspektrum wie klassische Opiate, z.B. eine analgetische Wirkung. Endorphine, oder genauer gesagt, die Enkephaline, sind unter anderem an verschiedenen, für die Schmerzperzeption und-transmission strategisch wichtigen Stellen des Zentralnervensystems lokalisiert. Vermutlich spielen sie unter gewissen Bedingungen bei der Regulation der Schmerzperzeption eine Rolle. Eine weitere Bedeutung dieser Substanzen scheint in der Regulation verschiedener neuroendokriner Prozesse zu liegen. Fraglicher ist ihre Signifikanz beim Zustandekommen bestimmter Symptome schizophrener Psychosen. Im Zustand der Opiat-Abhängigkeit konnten bisher keine nennenswerten Veränderungen des Enkephalin-Gehaltes festgestellt werden.