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Biomedical subjects

R L Johnson

Publications and source records attributed to R L Johnson.

At least 379 records · Page 21Linked to original sources
PubMed1977

Studies on vitamin D (calciferol) and its analogues. 10. Side-chain analogues of 25-hydroxyvitamin D3.

A homologous series of side-chain analogues of 25-hydroxyvitamin D3 (25-hydroxycholecalciferol) in which the length of the side chain is modified while maintaining its characteristic tertiary hydroxyl moiety has been synthesized. The following five analogues have been prepared and characterized: pentanor-25-OH-D3 (2a), trinor-25-OH-D3 (2b), dinor-25-OH-D3 (2c), nor-25-OH-D3 (2d), and homo-25-OH-D3 T2e). Biological assays in vivo of intestinal calcium absorption and bone calcium mobilization in the chick of the five analogues revealed that the homo analogue 2e exhibited a significant biological response relative to the -D (vitamin D3) control. Compared to the natural vitamin D3, 2e is as active in its ability to mobilize bone calcium and is about half as effective in stimulating intestinal calcium transport. The remaining analogues (2a-d) exhibited no significant activity in either assay, although the nor analogue 2d was previously observed to exhibit antimetabolite activity.

Animals↗
PubMed1977

Microscopic counting and adenosine 5'-triphosphate measurement in determining microbial growth in soils.

A microscopic technique utilizing dispersion of fungal hyphae in a Waring blender, filtration through membrane filters (Nucleopore Corp.), and counting on a fluorescence microscope was developed for counting fungal hyphal biomass. Nonfluorescent staining techniques of the soil-filter preparation did not give quantitative recoveries. Water-soluble aniline blue, which binds to the beta-1,3-glucans of the fungal cell wall, made visualization of the hyphae by fluorescence possible. A range of fungi added to soil were quantitatively recovered. Adenosine 5'-triphosphate (ATP) was extracted from soil by lysis of the organisms with CHCl(3) in NaHCO(3), which prevented adsorption of the organic phosphorus to the soil colloids. Centrifugation and removal of CHCl(3) was followed by dilution with pH 7.8 tris(hydroxymethyl)aminomethane buffer. ATP concentrations were measured by using the luciferase-luciferin light reaction. Since NaHCO(3) interfered to some extent with this reaction, the standards were made up in equivalent mixtures of tris(hydroxymethyl)aminomethane buffer and NaHCO(3). Recovery of ATP was rapid and quantitative in a range of soils. Measurement of the ATP and bacterial and fungal numbers in an incubated soil showed that fungal and bacterial population increases were delayed by phosphorus deficiency. Microbial populations were not affected at a later date. The ATP content of the soil system was reduced by phosphorus deficiency throughout the incubation period. This indicated that ATP could be altered without major changes in the microbial populations.

Adenosine Triphosphate↗
PubMed1977

Prostatic enlargement associated with symptomatic and asymptomatic gonorrhoea in adolescent men: An argument for routine rectal examination.

Ten adolescent men presented with prostatic enlargement and positive anterior urethral cultures for gonococci. Six of them had urethritis, but four were asymptomatic; the prostate is therefore implicated as a reservoir for the asymptomatic carrier and it is strongly recommended that the rectum should be included in the routine physical examination of sexually active adolescent men.

Adolescent↗
PubMed1977

The relationship of respiratory failure to the oxygen consumption of, lactate production by, and distribution of blood flow among respiratory muscles during increasing inspiratory resistance.

An animal model was developed to determine if blood flow to the respiratory muscles limits oxygen delivery and thus work output during inspiratory resistance. With incremental increases in the rate of work of breathing to 15 times the resting level, blood flow to the diaphragm rose exponentially 26-fold. Blood flow to other inspiratory and a few expiratory muscles increased to a much smaller extent, often only at the greater work loads. Cardiac output and blood pressure did not change. Arterial-venous oxygen content difference across the diaphragm became maximal at low work rates and thereafter all increases in oxygen delivery during higher work rates were accomplished by increments in blood flow. Oxygen consumption of the respiratory musculature calculated by blood flow times oxygen extraction increased exponentially with increasing work of breathing and was less than the increase in total body oxygen consumption at each work load. Hypoxemia and respiratory acidosis occurred when the animals inspired through the highest resistance; blood flow and oxygen consumption were even higher than that observed during previous resistances and there was no evidence of a shift to anaerobic metabolsim in blood lactate and pyruvate levels. Respiratory failure did not appear to be a consequence of insufficient blood flow in this model.

Airway Resistance↗
PubMed1977

The distribution of blood flow, oxygen consumption, and work output among the respiratory muscles during unobstructed hyperventilation.

An animal model was developed to describe respiratory muscle work output, blood flow, and oxygen consumption during mechanical ventilation, resting spontaneous ventilation, and the increased unobstructed ventilatory efforts induced by CO2 rebreathing. Almost all of the work of breathing was inspiratory work at all ventilatory levels; thus, only blood flows to the diaphragm and external intercostals increased in the transition from mechanical to spontaneous ventilation, and they further increased linearly as ventilatory work was incrementally augmented ninefold by CO2 rebreathing. No other muscles of inspiration manifest increased blood flows. A small amount of expiratory work was measured at high ventilatory volumes during which two expiratory muscles (transverse abdominal and intercostals) had moderate increases in blood flow. Blood pressure did not change, but cardiac output doubled. Arterial-venous oxygen content difference across the diaphragm increased progressively, so oxygen delivery was augmented by both increased blood flow and increased oxygen extraction at all work loads. Oxygen consumption increased linearly as work of breathing increased, so efficiency did not change significantly. The mean efficiency of the respiratory muscles was 15.5%. These results differ significantly from the patterns previously observed by us during increased work of breathing induced by inspiratory resistance, suggesting a different distribution of work load among the various muscles of respiration, a different fractionation of oxygen delivery between blood flow and oxygen extraction, and a higher efficiency when shortening, not tension development, of the muscle is increased.

Animals↗
PubMed1977

Respiratory muscle blood flow distribution during expiratory resistance.

When work load on the respiratory system is increased the relative increase in blood flow to each of the muscles of breathing provides an index of how the augmented effort of breathing is partitioned among the different muscles. We have used a radio-active microsphere technique to measure blood flow to each of the muscles of respiration in supine dogs during unobstructed respiration and breathing against graded expiratory threshold loads. 79% of the augmented flow went to expiratory muscles; of this increased flow to expiratory muscles 74% went to abdominal wall muscles and 26% to internal intercostals. In our earlier studies of hyperventilation induced by CO(2) rebreathing where expiratory work loads were low, 44% of the increase in flow went to expiratory muscles; of this, only 39% went to abdominal wall muscles and 61% to internal intercostals. During inspiratory resistance which produced small increases in expiratory work, 27% of the increase in blood flow went to expiratory muscles; of this, only 37% went to abdominal wall muscles and 63% to internal intercostals. These results suggest that the internal intercostals are predominantly used for expiration when expiratory work loads are low, whereas the abdominal wall muscles are predominantly used when loads are high. For similar rates of pressure-volume work done on the lung, the total respiratory muscle blood flow is significantly greater during expiratory loads than during unobstructed hyperventilation or inspiratory loads. Thus, the abdominal wall muscles that are utilized for overcoming high pressure expiratory loads are relatively inefficient in converting metabolic energy into pressure-volume work.

Airway Resistance↗
PubMed1977

Noninvasive determination of cardiac output by a modified acetylene rebreathing procedure utilizing mass spectrometer measurements.

A modified acetylene rebreathing technique for measuring cardiac output has been developed utilizing a mass spectrometer for measuring gas concentrations. Helium serves as an indicator of mixing and system volume. The disappearance rate of acetylene is proportional to pulmonary capillary blood flow, which is taken as an index of cardiac output. The method also provides an estimate of pulmonary tissue volume. The technique was assessed by comparing 22 simultaneous acetylene and dye-dilution cardiac outputs measured at rest and during exercise in six healthy subjects. There was no significant difference between the mean acetylene and dye-dilution cardiac output values (11.5 l/min vs. 11.24 l/min, respectively). The correlation coefficient was 0.94 and the S.E.M. difference was 0.53 l. The effect of the procedure on cardiac output was evaluated in a separate study of six subjects. There was a significant positive correlation between respiratory rate and cardiac output; but the magnitude of this effect was small, indicating that accurate measurements may be made at spontaneous respiratory rates.

Acetylene↗
PubMed1977

Mechanism of action of anticoagulants: correlation between the inhibition of prothrombin synthesis and the regeneration of vitamin K1 from vitamin K1 epoxide.

It has been proposed that coumarin and indandione anticoagulants inhibit clotting protein synthesis by preventing the regeneration of vitamin K1 from its 2,3-epoxide metabolic. To test this hypothesis, the effects of nine coumarin and indandiones on prothrombin synthesis and the conversion of vitamin K1 epoxide to vitamin K1 were measured. There was a good correlation between the inhibition of prothrombin synthesis and the epoxide-K1 conversion both in vivo and in vitro. Diphenadione (2-diphenyl acetyl-1,3-indandione) caused a delayed inhibition of prothrombin synthesis which correlated with a delayed inhibition of the epoxide-K1 conversion in vivo. These results provide strong evidence for the proposed mechanism of action of coumarin and indandione anticoagulants.

Animals↗
PubMed1976

The chemistry and conformational and biological analysis of vitamin D3, its metabolites and analogues.

The chemical properties, stereochemical relationships and solution conformation, as assessed in part by proton NMR spectroscopy, for vitamin D3, its major metabolites [including 1alpha,25-(OH)2D3, its hormonally active form] and a number of A-ring and side chain analogues are evaluated and discussed in relation to their biological activity. In particular the relative ability of many of these seco-steroids to compete both with 25-OHD3 for its chick serum binding protein and 1alpha,25-(OH)2-D3 for its chick intestinal cytosol-chromatin receptor system was quantitated, in vitro. Further, the relative effectiveness of all these metabolites and analogues to mediate in vivo intestinal calcium absorption and bone calcium mobilization was determined. Collectively these chemical and biological studies constitute a "systems analysis" of the various steroid structural parameters both required and tolerated by the multi-stepped endocrine system associated with the biological actions of vitamin D.

Animals↗
PubMed1976

Lymphokine stimulation of collagen accumulation.

Lymphokine-rich supernates from normal human peripheral blood mononuclear cells, stimulated by the mitogen phytohemagglutinin, have been shown to cause enhanced collagen accumulation by human embryonic lung fibroblasts (WI-38), as measured by hydroxyproline content of fibroblast monolayers, [14C] proline incorporation into soluble collagen and collagenase release of radioactivity in supernates and monolayers of cultures incubated with [14C] proline. This fibroblast-stimulating activity, demonstrable by suitable dilutions of the supernates, coexisted with a number of other lymphokine activities such as lymphotoxin, proliferation inhibitory factor, and cloning inhibitory factor, which tend to reduce the numbers of function of fibroblasts. The increased content of collagen appeared to be the product of selected surviving and responding fibroblasts. The factor causing this increased collagen accumulation was nondialyzable and stable at -70 degrees C. It represents the first described lymphoid cell-derived activity capable of enhancing collagen accumulation. Fibroblast-stimulating activity may be implicated in the abnormal fibrosis seen in association with chronic inflammation in a variety of disease states. It may have special relevance to progressive systemic sclerosis.

Cell Line↗