Effects from repeated short-term inhalation of fluorine.
Effects on lungs, livers, and kidneys of mice, rats, and rabbits from repeated short-term inhalation of fluorine
FLUORINE↗
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Evidence of SV40 infections in hospitalized children
Simian virus 40 (SV40) is known to have contaminated poliovirus vaccines used between 1955 and 1963. Accumulating reports have described the presence of SV40 DNA in human tumors and normal tissues, although the significance of human infections by SV40 is unknown. We investigated whether unselected hospitalized children had evidence of SV40 infections and whether any clinical correlations were apparent. Serum samples were examined for SV40 neutralizing antibody using a specific plaque reduction test; of 337 samples tested, 20 (5.9%) had antibody to SV40. Seropositivity increased with age and was significantly associated with kidney transplants (6 of 15 [40%] positive, P < .001). Many of the antibody-positive patients had impaired immune systems. Molecular assays (polymerase chain reaction and DNA sequence analysis) on archival tissue specimens confirmed the presence of SV40 DNA in 4 of the antibody-positive patients. This study, using 2 independent assays, shows the presence of SV40 infections in children born after 1980. We conclude that SV40 causes natural infections in humans.
NASA Discipline Regulatory Physiology↗
Citrate and renal calculi: an update
Citrate is an inhibitor of the crystallization of stone-forming calcium salts. Hypocitraturia, frequently encountered in patients with nephrolithiasis, is therefore an important risk factor for stone formation. Potassium citrate provides physiological and physicochemical correction and inhibits new stone formation, not only in hypocitraturic calcium nephrolithiasis but also in uric acid nephrolithiasis. Inhibition of stone recurrence has now been validated by a randomized trial. Ongoing research has disclosed additional causes of hypocitraturia (sodium excess, low intestinal alkali absorption, but not primary citrate malabsorption). Moreover, new insights on potassium citrate action have been shown, notably that some of absorbed citrate escapes oxidation and contributes to the citraturic response, that ingestion with a meal does not sacrifice physiological or physicochemical action, that orange juice mimics but does not completely duplicate its actions, that potassium citrate may have a beneficial bone-sparing effect, that it may reduce stone fragments following ESWL, and that danger of aluminum toxicity is not great in subjects with functioning kidneys. Finally, the research on potassium citrate has led to two promising products, calcium citrate as an optimum calcium supplement and potassium-magnesium citrate which may be superior to potassium citrate in the management of stone disease.
NASA Discipline Regulatory Physiology↗
Genome-wide transcriptional analysis of flagellar regeneration in Chlamydomonas reinhardtii identifies orthologs of ciliary disease genes
The important role that cilia and flagella play in human disease creates an urgent need to identify genes involved in ciliary assembly and function. The strong and specific induction of flagellar-coding genes during flagellar regeneration in Chlamydomonas reinhardtii suggests that transcriptional profiling of such cells would reveal new flagella-related genes. We have conducted a genome-wide analysis of RNA transcript levels during flagellar regeneration in Chlamydomonas by using maskless photolithography method-produced DNA oligonucleotide microarrays with unique probe sequences for all exons of the 19,803 predicted genes. This analysis represents previously uncharacterized whole-genome transcriptional activity profiling study in this important model organism. Analysis of strongly induced genes reveals a large set of known flagellar components and also identifies a number of important disease-related proteins as being involved with cilia and flagella, including the zebrafish polycystic kidney genes Qilin, Reptin, and Pontin, as well as the testis-expressed tubby-like protein TULP2.
Polycystic Kidney Diseases/genetics↗
Probabilistic Modeling of the Renal Stone Formation Module
The Integrated Medical Model (IMM) is a probabilistic tool, used in mission planning decision making and medical systems risk assessments. The IMM project maintains a database of over 80 medical conditions that could occur during a spaceflight, documenting an incidence rate and end case scenarios for each. In some cases, where observational data are insufficient to adequately define the inflight medical risk, the IMM utilizes external probabilistic modules to model and estimate the event likelihoods. One such medical event of interest is an unpassed renal stone. Due to a high salt diet and high concentrations of calcium in the blood (due to bone depletion caused by unloading in the microgravity environment) astronauts are at a considerable elevated risk for developing renal calculi (nephrolithiasis) while in space. Lack of observed incidences of nephrolithiasis has led HRP to initiate the development of the Renal Stone Formation Module (RSFM) to create a probabilistic simulator capable of estimating the likelihood of symptomatic renal stone presentation in astronauts on exploration missions. The model consists of two major parts. The first is the probabilistic component, which utilizes probability distributions to assess the range of urine electrolyte parameters and a multivariate regression to transform estimated crystal density and size distributions to the likelihood of the presentation of nephrolithiasis symptoms. The second is a deterministic physical and chemical model of renal stone growth in the kidney developed by Kassemi et al. The probabilistic component of the renal stone model couples the input probability distributions describing the urine chemistry, astronaut physiology, and system parameters with the physical and chemical outputs and inputs to the deterministic stone growth model. These two parts of the model are necessary to capture the uncertainty in the likelihood estimate. The model will be driven by Monte Carlo simulations, continuously randomly sampling the probability distributions of the electrolyte concentrations and system parameters that are inputs into the deterministic model. The total urine chemistry concentrations are used to determine the urine chemistry activity using the Joint Expert Speciation System (JESS), a biochemistry model. Information used from JESS is then fed into the deterministic growth model. Outputs from JESS and the deterministic model are passed back to the probabilistic model where a multivariate regression is used to assess the likelihood of a stone forming and the likelihood of a stone requiring clinical intervention. The parameters used to determine to quantify these risks include: relative supersaturation (RS) of calcium oxalate, citrate/calcium ratio, crystal number density, total urine volume, pH, magnesium excretion, maximum stone width, and ureteral location. Methods and Validation: The RSFM is designed to perform a Monte Carlo simulation to generate probability distributions of clinically significant renal stones, as well as provide an associated uncertainty in the estimate. Initially, early versions will be used to test integration of the components and assess component validation and verification (V&V), with later versions used to address questions regarding design reference mission scenarios. Once integrated with the deterministic component, the credibility assessment of the integrated model will follow NASA STD 7009 requirements.
kidney stones↗
Conversion of acetate to lipids and CO sub 2 by liver of rats exposed to acceleration stress.
Acetate conversion to lipids and carbon dioxide by liver, kidney and inguinal adipose tissues of rats under centrifugation stress
METABOLISM↗
Pathology of animals exposed for periods up to 92 days to a pure oxygen atmosphere at reduced pressure.
Lung, liver, kidney and heart pathology of dogs, monkeys, rats and mice exposed for 2 to 13 weeks to pure oxygen atmosphere at reduced pressure
ANIMAL STUDY↗
Fractionated heavy ion irradiation of cultured human cells.
Reparability of cultured human kidney cells injured by fractionated heavy ion irradiation
Todd, P.↗
Hypothalamic stimulus effects on sympathetic nerve activity
Hypothalamus stimulus effects on sympathetic nerve activity to heart, spleen, kidney and leg skeletal muscle in anesthetized cats
Judy, W. V.↗
Effect of thyroxine on the cell generation cycle parameters of cultured human cells
Human kidney cell generation and life cycle parameters, considering thyroxine effects
Burki, H. J.↗
Research to determine the role of gravity in neurosecretory physiology
In an effort to determine the effects of gravity in regulating the synthesis, transport, storage, and release of octopeptides from the hypothalamo-neurophypophyseal system, the teleost fresh water fish was studied. A labyrinthectomized fish was subjected to a gravitational orientation of -G sub z for three days. Results show the fish had reduced levels of adenyl cyclose activity in its kidneys when compared to labyrinthectomized and unoperated fish exposed to normal gravitational orientation (+G sub 2) for the same period of time. Efforts were also made to determine the presence of vasopressin in the neurophypophysis and peripheral target organs.
Clemens, L. E.↗
Continuous animal exposure to dichloromethane
Continuous exposures of dogs, monkeys, rats and mice to 5000 ppm and 1000 ppm of dichloromethane vapor (CH2Cl2) produced severe toxic effects on dogs, rats and mice. Dogs died after 3 weeks exposure to 1000 ppm and after 6 weeks exposure to 5000 ppm. Thirty percent of the mice also succumbed during four weeks exposure to 5000 ppm CH2Cl2. Although rats survived 14 weeks exposure to 5000 ppm, they experienced subnormal weight gains. Significant gross and histopathological hepatic lesions were noted in all 3 species at death or experimental termination in 14 weeks. In addition, rats showed abnormal kidney histopathology. Fat stains disclosed mild fatty increase in monkey livers after 14 weeks exposure to 1000 ppm CH2Cl2.
Macewen, J. D.↗
Applications of aerospace technology in the public sector
Current activities of the program to accelerate specific applications of space related technology in major public sector problem areas are summarized for the period 1 June 1971 through 30 November 1971. An overview of NASA technology, technology applications, and supporting activities are presented. Specific technology applications in biomedicine are reported including cancer detection, treatment and research; cardiovascular diseases, diagnosis, and treatment; medical instrumentation; kidney function disorders, treatment, and research; and rehabilitation medicine.
Anuskiewicz, T.↗
Pulmonary Edema and Plasma Volume Changes in Dysbarism
Two groups of anesthetized, fasted pigs were utilized. One group of 13 animals (8.5 to 16.6 kilograms) was exposed to a high-pressure environment, and the other group of eight animals (6.9 to 20.0 kilograms) constituted the control group. The experimental group was subjected to an atmosphere of 90 percent nitrogen and 10 percent oxygen at a pressure of 50 psig for 30 minutes and then decompressed at a rate 10 psi/min. Plasma volumes, using both iodine-125-tagged-albumin and chromium-51-tagged-cell dilution techniques, were measured before, immediately after, and at 30 and 60 minutes after decompression. Aortic and right-ventricular systolic pressures were also recorded. At 60 minutes after decompression, blood samples were taken, the animals were sacrificed, and the water content of the lungs, kidneys, livers, and spleens was estimated by measuring tissue wet weight and dry weight. Protein extravasation and tissue blood volumes were determined by measuring the iodine-125-tagged-albumin and chromium-51-tagged-cell spaces in homo-genates of the organs under investigation.
Joki, J. A.↗
Applicability of implantable telemetry systems in cardiovascular research.
This paper briefly describes the results of an experimental program undertaken to develop and apply implanted telemetry to cardiovascular research. Because of the role the kidney may play in essential hypertension, emphasis is placed on telemetry's applicability in the study of renal physiology. Consequently, the relationship between pressure, flow, and hydraulic impedance are stressed. Results of an exercise study are given.
Krutz, R. W.↗
Biomedical findings on American astronauts participating in space missions.
Zero-gravity adaptive responses of man are discussed on the basis of biomedical data for 54 American astronauts, covering performance, locomotion, orientation, sleep and physiological and functional characteristics. Figures and diagrams are given for cardiovascular adaptation, weight loss, endocrine and electrolyte responses, fluid balance, skeletal responses, muscular and neuromuscular changes, exercise response tests and work capacity indicators. A review is given of current hypotheses concerning the processes involved in human adaptation to zero gravity. It is concluded that the immediate response of the body to weightlessness is a redistribution of the total circulating blood volume, leading to a loss of water, sodium and potassium through the kidneys and, thus, to a loss in total body weight.
Berry, C. A.↗
Role of distal reabsorption and peritubular environment in glomerulotubular balance.
Total kidney glomerulotubular balance was examined during aortic constriction and release in saline-loaded dogs and in dogs undergoing water diuresis. Aortic constriction lowered the glomerular filtration rate by 45% in both groups, and glomerulotubular balance, as judged by changes in absolute sodium reabsorption, was also comparable. During water diuresis, a linear relationship was observed between free water clearance and urine flow during all maneuvers, suggesting that distal sodium reabsorption is related primarily to distal delivery. The results suggest that if alterations in the peritubular environment are responsible for the changes in tubular sodium reabsorption during aortic constriction in the saline- or water-loaded dog, then a change in renal plasma flow, and presumably delivery rate of oncotic force, may be the most likely mediator.
Schrier, R. W.↗