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At least 55 records · Page 3

Histamine H2 receptor - Involvement in gastric ulceration

The involvement of the H1 and H2 receptors for histamine in the pathogenesis of gastric ulcers was investigated in rats. Metiamide, an H2 receptor antagonist, reliably reduced ulceration produced by stress alone or by a combination of stress and aspirin. In contrast, pyrilamine, which blocks only the H1 receptor, was without effect under these same conditions. The results support the hypothesis that histamine mediates both stress and stress plus aspirin induced ulceration by a mechanism involving the H2 receptor.

Brown, P. A.↗

Pathophysiological aspects of the problem of prolonged hypokinesia

The changes in man's acitivity due to modern life with automation and sedentary activities and man's exploration of space in a state of weightlessness have accentuated the importance of hypokinesia. The pathogenesis of hypokinesia is discussed. Experiments and results made on man and animals are included.

Kovalenko, Y. A.↗

Review of book vestibular crises

The etiology, pathogenesis, clinical practice, treatment and rehabilitation of patients with vestibular crises is discussed. Classifications for vestibular disorders are given. Information on the frequency of vestibular crises is given.

Blagoveshchenskaya, N. S.↗

Study on contraction and relaxation of experimentally denervated and immobilized muscles: Comparison with dystrophic muscles

The contraction-relaxation mechanism of experimentally denervated and immobilized muscles of the rabbit is examined. Results are compared with those of human dystrophic muscles, in order to elucidate the role and extent of the neurotrophic factor, and the role played by the intrinsic activity of muscle in connection with pathogenesis and pathophysiology of this disease.

Takamori, M.↗

Effects of rectilinear acceleration, optokinetic and caloric stimuli in space

The set of experiments comprising the Spacelab 1ES201 package designed to investigate the human vestibular system and equilibratory function in weightlessness are described. The specific objectives of the experiments include: (1) the determination of the threshold of perception of linear oscillatory motion; (2) measurement of physiological and subjective responses to supra threshold, linear and angular motion stimuli; (3) study of the postural adjustments, eye movements, and illusions of attitude and motion evoked by optokinetic stimuli, (i.e., moving visual patterns) in order to assess visual/vestibular interactions; (4) examination of the effect of thermal stimulations of the vestibular apparatus to determine if the eye movements elicited by the 'caloric test' are used by a density gradient in the semicircular canal; and (5) investigation of the pathogenesis of space motion sickness by recording signs and symptoms during the course of vestibular stimulation and, specifically, when the test subject is exposed to sustained, linear oscillatory motion.

Vonbaumgarten, R.↗

Research opportunities in bone demineralization, phase 3

An overview of bone demineralization during space flight, observations in bone demineralization and experiments related to bone loss planned for Spacelab flights, and suggestions for further research are investigated. The observations of the working group focused upon the following topics: (1) pathogenesis of bone demineralization, (2) potential for occurrence of renal stones consequent to prolonged hypercalciuria, (3) development of appropriate ground based and inflight models to study bone demineralization, (4) integration of research efforts, and (5) development of effective countermeasures.

Anderson, S. A.↗

Flow cytometry analysis of hormone receptors on human peripheral blood mononuclear cells to identify stress-induced neuroendocrine effects

Understanding the role of circulating peptide hormones in the pathogenesis of space-flight induced disorders would be greatly facilitated by a method which monitors chronic levels of hormones and their effects upon in vivo cell physiology. Single and simultaneous multiparameter flow cytometry analysis was employed to identify subpopulations of mononuclear cells bearing receptors for ACTH, Endorphin, and Somatomedin-C using monoclonal antibodies and monospecific antisera with indirect immunofluorescence. Blood samples were obtained from normal donors and subjects participating in decompression chamber studies (acute stress), medical student academic examination (chronic stress), and a drug study (Dexamethasone). Preliminary results indicate most ACTH and Endorphin receptor positive cells are monocytes and B-cells, exhibit little diurnal variation but the relative percentages of receptor positive cells are influenced by exposure to various stressors and ACTH inhibition. This study demonstrates the capability of flow cytometry analysis to study cell surface hormone receptor regulation which should allow insight into neuroendocrine modulation of the immune and other cellular systems during exposure to stress or microgravity.

Meehan, R. T.↗

Hyperbaric hyperoxia reversibly inhibits erythrocyte phospholipid fatty acid turnover

The effect of hyperbaric hyperoxia on the acylation of membrane phospholipid was studied by measuring the rates of activation of exogenous tritiated oleic acid to acyl thioester and of transesterification of the thioester into membrane phospholipids in intact human erythrocytes obtained 1 h after an exposure of the subjects to a hyperbaric oxygen atmosphere (3.5 h, 100 pct O2, 3 ATA). Exposure to pure oxygen was found to inhibit both the acylation and transesterification reactions by more than 30 percent, with partial recovery detected 24 h later. On the other hand, no rate changes were observed when isolated membranes from the same batches of cells were used in similar experiments. It is suggested that the decrease in the incorporation of tritiated oleic acid after hyperbaric hyperoxia may reflect an early event in the pathogenesis of oxygen-induced cellular injury and that it may be a useful index for the assessment of the tolerance of tissues to hyperoxia.

Dise, Craig A.↗

Dynamics of microorganism populations in recirculating nutrient solutions

This overview covers the basic microbial ecology of recirculating hydroponic solutions. Examples from NASA and Soviet Controlled Ecological Life Support Systems (CELSS) tests and the commercial hydroponic industry will be used. The sources of microorganisms in nutrient solutions include air, water, seeds, plant containers and plumbing, biological vectors, and personnel. Microbial fates include growth, death, and emigration. Important microbial habitats within nutrient delivery systems are root surfaces, hardware surfaces (biofilms), and solution suspension. Numbers of bacteria on root surfaces usually exceed those from the other habitats by several orders of magnitude. Gram negative bacteria dominate the microflora with fungal counts usually much lower. Trends typically show a decrease in counts with increasing time unless stressed plants increase root exudates. Important microbial activities include carbon mineralization and nitrogen transformations. Important detrimental interactions include competition with plants, and human and plant pathogenesis.

Strayer, R. F.↗

Dynamics of microorganism populations in recirculating nutrient solutions

This overview covers the basic microbial ecology of recirculating hydroponic solutions. Examples from NASA and Soviet CELSS tests and the commercial hydroponic industry will be used. The sources of microorganisms in nutrient solutions include air, water, seeds, plant containers and plumbing, biological vectors, and personnel. Microbial fates include growth, death, and emigration. Important microbial habitats within nutrient delivery systems are root surfaces, hardware surfaces (biofilms), and solution suspension. Numbers of bacteria on root surfaces usually exceed those from the other habitats by several orders of magnitude. Gram negative bacteria dominate the microflora with fungal counts usually much lower. Trends typically show a decrease in counts with increasing time unless stressed plants increase root exudates. Important microbial activities include carbon mineralization and nitrogen transformations. Important detrimental interactions include competition with plants, and human and plant pathogenesis.

Strayer, R. F.↗

Epstein-Barr virus DNA loads in adult human immunodeficiency virus type 1-infected patients receiving highly active antiretroviral therapy

Patients with human immunodeficiency virus type 1 (HIV-1) infection are at high risk of developing Epstein-Barr virus (EBV)-associated lymphoma. However, little is known of the EBV DNA loads in patients receiving highly active antiretroviral therapy (HAART). Using a real-time quantitative polymerase chain reaction assay, we demonstrated that significantly more HIV-1-infected patients receiving HAART than HIV-1-uninfected volunteers had detectable EBV DNA in blood (57 [81%] of 70 vs. 11 [16%] of 68 patients; P=.001) and saliva (55 [79%] of 68 vs. 37 [54%] of 68 patients; P=.002). The mean EBV loads in blood and saliva samples were also higher in HIV-1-infected patients than in HIV-1-uninfected volunteers (P=.001). The frequency of EBV detection in blood was associated with lower CD4+ cell counts (P=.03) among HIV-1-infected individuals, although no differences were observed in the EBV DNA loads in blood or saliva samples in the HIV-1-infected group. Additional studies are needed to determine whether EBV-specific CD4+ and CD8+ cells play a role in the pathogenesis of EBV in HIV-1-infected patients receiving HAART.

NASA Discipline Regulatory Physiology↗

Nitric oxide in microgravity-induced orthostatic intolerance: relevance to spinal cord injury

Prolonged exposure to microgravity results in cardiovascular deconditioning which is marked by orthostatic intolerance in the returning astronauts and recovering bed-ridden patients. Recent studies conducted in our laboratories at University of California, Irvine have revealed marked elevation of nitric oxide (NO) production in the kidney, heart, brain, and systemic arteries coupled with significant reduction of NO production in the cerebral arteries of microgravity-adapted animals. We have further demonstrated that the observed alteration of NO metabolism is primarily responsible for the associated cardiovascular deconditioning. Recovery from acute spinal cord injury (SCI) is frequently complicated by orthostatic intolerance that is due to the combined effects of the disruption of efferent sympathetic pathway and cardiovascular deconditioning occasioned by prolonged confinement to bed. In this presentation, I will review the nature of altered NO metabolism and its role in the pathogenesis of microgravity-induced cardiovascular deconditioning. The possible relevance of the new findings to orthostatic intolerance in patients with acute SCI and its potential therapeutic implications will be discussed.

Review↗

Basic and clinical immunology

Progress in immunology continues to grow exponentially every year. New applications of this knowledge are being developed for a broad range of clinical conditions. Conversely, the study of primary and secondary immunodeficiencies is helping to elucidate the intricate mechanisms of the immune system. We have selected a few of the most significant contributions to the fields of basic and clinical immunology published between October 2001 and October 2002. Our choice of topics in basic immunology included the description of T-bet as a determinant factor for T(H)1 differentiation, the role of the activation-induced cytosine deaminase gene in B-cell development, the characterization of CD4(+)CD25(+) regulatory T cells, and the use of dynamic imaging to study MHC class II transport and T-cell and dendritic cell membrane interactions. Articles related to clinical immunology that were selected for review include the description of immunodeficiency caused by caspase 8 deficiency; a case series report on X-linked agammaglobulinemia; the mechanism of action, efficacy, and complications of intravenous immunoglobulin; mechanisms of autoimmunity diseases; and advances in HIV pathogenesis and vaccine development. We also reviewed two articles that explore the possible alterations of the immune system caused by spaceflights, a new field with increasing importance as human space expeditions become a reality in the 21st century.

Review↗

Disuse exaggerates the detrimental effects of alcohol on cortical bone

BACKGROUND: Alcohol abuse is associated with an increased risk for osteoporosis. However, comorbidity factors may play an important role in the pathogenesis of alcohol-related bone fractures. Suboptimal mechanical loading of the skeleton, an established risk factor for bone loss, may occur in some alcohol abusers due to reduced physical activity, muscle atrophy, or both. The effect of alcohol consumption and reduced physical activity on bone metabolism has not been well studied. The purpose of this study was to determine whether mechanical disuse alters bone metabolism in a rat model for chronic alcohol abuse. METHODS: Alcohol was administered in the diet (35% caloric intake) of 6-month-old male rats for 4 weeks. Rats were hindlimb-unloaded the final 2 weeks of the experiment to prevent dynamic weight bearing. Afterward, cortical bone histomorphometry was evaluated at the tibia-fibula synostosis. RESULTS: At the periosteal surface of the tibial diaphysis, alcohol and hindlimb unloading independently decreased the mineralizing perimeter, mineral apposition rate, and bone formation rate. In addition, alcohol, but not hindlimb unloading, increased endocortical bone resorption. The respective detrimental effects of alcohol and hindlimb unloading to inhibit bone formation were additive; there was no interaction between the two variables. CONCLUSIONS: Reduced weight bearing accentuates the detrimental effects of alcohol on cortical bone in adult male rats by further inhibiting bone formation. This finding suggests that reduced physical activity may be a comorbidity factor for osteoporosis in alcohol abusers.

NASA Discipline Cell Biology↗

Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells

Several proteins implicated in the pathogenesis of polycystic kidney disease (PKD) localize to cilia. Furthermore, cilia are malformed in mice with PKD with mutations in TgN737Rpw (encoding polaris). It is not known, however, whether ciliary dysfunction occurs or is relevant to cyst formation in PKD. Here, we show that polycystin-1 (PC1) and polycystin-2 (PC2), proteins respectively encoded by Pkd1 and Pkd2, mouse orthologs of genes mutated in human autosomal dominant PKD, co-distribute in the primary cilia of kidney epithelium. Cells isolated from transgenic mice that lack functional PC1 formed cilia but did not increase Ca(2+) influx in response to physiological fluid flow. Blocking antibodies directed against PC2 similarly abolished the flow response in wild-type cells as did inhibitors of the ryanodine receptor, whereas inhibitors of G-proteins, phospholipase C and InsP(3) receptors had no effect. These data suggest that PC1 and PC2 contribute to fluid-flow sensation by the primary cilium in renal epithelium and that they both function in the same mechanotransduction pathway. Loss or dysfunction of PC1 or PC2 may therefore lead to PKD owing to the inability of cells to sense mechanical cues that normally regulate tissue morphogenesis.

Non-NASA Center↗

Differential effects of catecholamines on in vitro growth of pathogenic bacteria

Supplementation of minimal medium inoculated with bacterial cultures with norepinephrine, epinephrine, dopamine, or isoproterenol resulted in marked increases in growth compared to controls. Norepinephrine and dopamine had the greatest enhancing effects on growth of cultures of Pseudomonas aeruginosa and Klebsiella pneumoniae, while epinephrine and isoproterenol also enhanced growth to a lesser extent. The growth of Escherichia coli in the presence of norepinephrine was greater than growth in the presence of the three other neurochemicals used in the study. Growth of Staphylococcus aureus was also enhanced in the presence of norepinephrine, but not to the same degree as was the growth of gram negative bacteria. Addition of culture supernatants from E. coli cultures that had been grown in the presence of norepinephrine was able to enhance the growth of K. pneumoniae. Addition of the culture supernatant fluid culture from E. coli cultures that had been grown in the presence of norepinephrine did not enhance growth of P. aeruginosa or S. aureus. Culture supernatant fluids from bacteria other than E. coli grown in the presence of norepinephrine were not able to enhance the growth of any bacteria tested. The results suggest that catecholamines can enhance growth of pathogenic bacteria, which may contribute to development of pathogenesis; however, there is no uniform effect of catecholamines on bacterial growth.

Non-NASA Center↗

G-induced vestibular dysfunction ('the wobblies') among aerobatic pilots: a case report and review

G-induced vestibular dysfunction (GIVD) is a condition well known to aircraft pilots who experience high positive and negative G loads during unlimited-aerobatic competitions and air-show demonstrations. After landing and walking from their aircraft, pilots with GIVD manifest an extremely unstable gait, which they call the wobblies. This article includes a report of one such case of GIVD, which to the author's knowledge is the first published case report of this condition in the medical literature. The author also discusses what is known and theorized about the pathogenesis of GIVD, and he reviews its diagnosis, treatment, and prevention.

Case Reports↗