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Biomedical subjects

M J Welsh

Publications and source records attributed to M J Welsh.

320 records · Page 18Linked to original sources
PubMed1980

Fluid transport across the canine tracheal epithelium.

We measured the rate of fluid movement across the tracheal epithelium of the dog by an electrical method, modified from that originally described by Wiedner (Rev. Sci. Instrum. 47: 775-6, 1976). The base-line volume flow (Jv) from the submucosa to the mucosa was 44 +/- 23 nl.min-1.cm-2 (mean +/- SE; n = 6). In only three of the tissues was the resting Jv significantly greater than zero. Stimulation with 2 X 10(-3) M aminophylline (a drug that we have shown stimulates Cl secretion under short-circuit conditions) increased Jv in all tissues to a mean of 137 +/- 29 nl.min-1.cm-2 (P < 0.001). We also measured the unidirectional fluxes of Cl with the tissue at its spontaneous electrical potential. During the base-line period, the net flux of Cl was not significantly different from zero. During stimulation with aminophylline, Cl secretion increased to a mean of 1.44 +/- 0.50 microneq.cm-2.h-1. Comparison of the stimulated values of Jv and net Cl secretion suggests that fluid secretion by the trachea is isotonic during stimulation with aminophylline.

Aminophylline↗
PubMed1980

Ion transport by dog tracheal epithelium.

The dog's tracheal epithelium actively transports Cl towards the lumen and Na towards the serosa. In this review the effects of various drugs on these ion transport processes are described and possible mechanisms for Na and Cl transport are discussed.

Amiloride↗
PubMed1979

Tubulin and calmodulin. Effects of microtubule and microfilament inhibitors on localization in the mitotic apparatus.

Indirect immunofluorescence was used to determine the distribution of calmodulin in the mitotic apparatus of rat kangaroo PtK2 and Chinese hamster ovary (CHO) cells. The distribution of calmodulin in PtK2 cells was compared to the distribution of tubulin, also as revealed by indirect immunofluorescence. During mitosis, calmodulin was found to be a dynamic component of the mitotic apparatus. Calmodulin first appeared in association with the forming mitotic apparatus during midprophase. In metaphase and anaphase, calmodulin was found between the spindle poles and the chromosomes. While tubulin was found in the interzonal region throughout anaphase, calmodulin appeared in the interzone region only at late anaphase. The interzonal calmodulin of late anaphase condensed during telophase into two small regions, one on each side of the midbody. Calmodulin was not detected in the cleavage furrow. In view of the differences in the localization of calmodulin, tubulin, and actin in the mitotic apparatus, experiments were designed to determine the effects of various antimitotic drugs on calmodulin localization. Cytochalasin B, an inhibitor of actin microfilaments, had no apparent effect on calmodulin or tubulin localization in the mitotic apparatus of CHO cells. Microtubule inhibitors, such as colcemid and N2O, altered the appearance of tubulin- and calmodulin-specific fluorescence in mitotic CHO cells. Cold temperature (0 degrees C) altered tubulin-specific fluorescence of metaphase PtK2 cells but did not alter calmodulin-specific fluorescence. From these studies, it is concluded that calmodulin is more closely associated with the kinetichore-to-pole microtubules than other components of the mitotic apparatus.

Animals↗
PubMed1978

Calcium-dependent regulator protein: localization in mitotic apparatus of eukaryotic cells.

Calcium-dependent regulator protein is a low molecular weight (17,000), thermostable, calcium binding protein which is structurally homologous to skeletal muscle troponin C. This protein is present in all nonmuscle cells and has been shown to decorate stress fibers in interphase cells by indirect immunofluorescence. Using this procedure we have investigated the distribution of the protein during mitosis of eukaryotic cells. As the cells enter prophase, the distinct cytoplasmic localization disappears commensurate with the dissolution of the cytoskeleton. The regulator protein seems to be randomly distributed throughout the prophase cell, including the region around the condensed chromosomes. However, at prometaphase, it is localized in association with the half-spindles of the mitotic apparatus. Through metaphase and most of anaphase, the protein remains localized between the chromosomes and the poles of the spindle. During late anaphase the protein is also found in the interzone region but rapidly condenses into two small regions, one on each side of the midbody that separates the daughter cells. The regulator protein is not localized in the cleavage furrow during telophase, whereas actin is demonstrable in this region. Indeed, placement of the protein during mitosis is distinct from both that of actin and that of tubulin. The localization of calcium-dependent regulator protein during mitosis suggests that it may mediate the calcium effects on the mitotic apparatus and thus play a role in chromosome movement.

Actins↗
PubMed1978

Depression of ventilation by dopamine in man. Evidence for an effect on the chemoreceptor reflex.

Dopamine is present in the carotid body and has been postulated to be an inhibitory neurotransmitter. The purpose of this study was to determine the effects of dopamine on ventilation in man and to examine its mechanism of action. Dopamine (0.5-10 mug/kg per min) was infused in eight normal men at different levels of arterial chemoreceptor activity, produced by varying the inspired Po(2). During normoxia dopamine produced a small decrease in minute ventilation (Ve) and an increase in arterial Pco(2). When arterial chemoreceptors were stimulated by hypoxia, infusion of dopamine produced a marked initial depression of Ve followed by a sustained although less pronounced decrease in Ve. An increase in Pa(co) (2) and a decrease in Pao(2) were also observed. When arterial chemoreceptor activity was suppressed by hyperoxia, infusion of dopamine did not affect ventilation. Subjects also breathed a hypercarbic, hyperoxic gas mixture. The hypercarbia produces hyperventilation by stimulating central chemoreceptors, whereas the hyperoxia suppresses peripheral chemoreceptors. Dopamine did not alter ventilation while the subjects were breathing this gas mixture. These studies suggest that dopamine suppresses ventilation in man through an action on the arterial chemoreceptor reflex. These findings support the hypothesis that dopamine is an inhibitory neurotransmitter in the carotid body, and that release of dopamine may modulate the sensitivity of peripheral arterial chemoreceptors.

Adult↗
PubMed1977

Intravenous elemental mercury injection: blood levels and excretion of mercury.

The blood level and excretion of mercury was measured in a patient who injected 1 ml (13.6 g) of elemental mercury intravenously. The chest radiograph showed metallic densities delineating small pulmonary vessels. The patient had no signs or symptoms of mercury intoxication in the year after injection. Mercury blood levels were essentially constant, averaging 62 ng/ml. Although exhalation of mercury vapor was a major route of excretion and urinary mercury rose fivefold with administration of penicillamine, excretion by all routes, estimated for the year after injection, represented only 1% of the dose. Total body clearance of mercury wasonly 5 ml/min. Penicillamine therefore appeared to be of little value in reducing the body burden of mercury. The data also suggest that acute systemic mercury intoxication is unlikely after intravascular elemental mercury injection because blood mercury levels are low.

Adult↗
PubMed1975

Rat sertoli cells: a rapid method for obtaining viable cells.

A method is described for obtaining populations of viable Sertoli cells from rat testes. Minced whole testes from rats of 15 to 29 days of age are sequentially treated with collagenase and pancreatin. The resulting suspension of cells is sedimented through a sucrose density gradient. Preparations are produced consisting of from 60% to 82% Sertoli cells, an enrichment of 2 to 5 times the proportion of Sertoli cells in whole testes of these ages. The preparations are free of interstitial cells, are essentially free of peritubular cells and contain reduced numbers of germinal cells; the main contaminating cell types are spermatogonia and spermatocytes. The Sertoli cells are considered to be 95% viable by their ability to exclude trypan blue and by subsequent culturing in vitro. The entire procedure requires 3 h. Maintenance of the Sertoli-enriched fraction in modified Eagle's minimal essential medium temporarily at 41 C allows preparations of Sertoli cell monolayer cultures consisting of 95%-98% Sertoli cells within 3 days.

Animals↗
PubMedDate not supplied

Chloride and potassium channels in cystic fibrosis airway epithelia.

Cystic fibrosis, the most common lethal genetic disease in Caucasians, is characterized by a decreased permeability in sweat gland duct and airway epithelia. In sweat duct epithelium, a decreased Cl- permeability accounts for the abnormally increased salt content of sweat. In airway epithelia a decreased Cl- permeability, and possibly increased sodium absorption, may account for the abnormal respiratory tract fluid. The Cl- impermeability has been localized to the apical membrane of cystic fibrosis airway epithelial cells. The finding that hormonally regulated Cl- channels make the apical membrane Cl- permeable in normal airway epithelial cells suggested abnormal Cl- channel function in cystic fibrosis. Here we report that excised, cell-free patches of membrane from cystic fibrosis epithelial cells contain Cl- channels that have the same conductive properties as Cl- channels from normal cells. However, Cl- channels from cystic fibrosis cells did not open when they were attached to the cell. These findings suggest defective regulation of Cl- channels in cystic fibrosis epithelia; to begin to address this issue, we performed two studies. First, we found that isoprenaline, which stimulates Cl- secretion, increases cellular levels of cyclic AMP in a similar manner in cystic fibrosis and non-cystic fibrosis epithelial cells. Second, we show that adrenergic agonists open calcium-activated potassium channels, indirectly suggesting that calcium-dependent stimulus-response coupling is intact in cystic fibrosis. These data suggest defective regulation of Cl- channels at a site distal to cAMP accumulation.

Calcium↗