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Biomedical subjects

M D Johnson

Publications and source records attributed to M D Johnson.

At least 271 records · Page 15Linked to original sources
PubMed1984

The importance of age on prostaglandin E2 excretion in normal and hypertensive men.

Previous studies have shown reduced levels and total urinary excretion of prostaglandin E2 in a heterogeneous population of patients with hypertension. The following study was undertaken to extend these observations to focus on the influence of age and blood pressure on renal prostaglandin E2 excretion in males. Four groups of human subjects were studied on an ad libitum diet of at least 2 g salt per day: group 1 consisted of normal young men; group 2 consisted of young men with essential hypertension; group 3 consisted of older nonhypertensive men; group 4 consisted of older hypertensive men. Reduced urinary prostaglandin E2 excretion was seen in the elderly hypertensive group but not the young hypertensives. Thus, when all hypertensives were compared to control the reduced prostaglandin E2 excretion was accounted for primarily by the elderly hypertensives. The reduction of prostaglandin E2 excretion could not be accounted for by normal ageing alone. Whether cause or effect, alterations of renal prostaglandin physiology accompanied hypertension in elderly men. No clear alteration of prostaglandin E2 physiology was noted in young male hypertensives.

Adult↗
PubMed1984

Saralasin acetate test in renal transplant hypertension. Report of 17 cases and a review of the literature.

The saralasin acetate test was performed in 17 hypertensive patients with renal transplants. These results were compared with 39 previously published reports of transplant patients who had been tested in the same manner. Eighty-two percent of our patients had a positive saralasin acetate test, suggesting renin-dependent hypertension. Baseline plasma renin activity (PRA) was significantly higher in patients with positive tests (6.96 +/- 1.75 v 2.88 +/- 0.53 ng/mL/hr). However, positive tests were obtained in several patients who had normoreninemia, and PRA levels did not correlate with the magnitude of vasodepressor BP response to saralasin. Transplant artery stenosis, acute rejection, and chronic rejection were the most common posttransplant complications associated with a positive test, but several patients had hypertension alone. While highly sensitive for renin-dependent hypertension posttransplantation, the test had poor specificity for identification of any one cause of posttransplant hypertension.

Blood Pressure↗
PubMed1984

Non-renin dependent hypertension in renal allograft rejections. A structural and functional analysis.

A 25-year-old recipient of a cadaveric renal allograft underwent three acute rejection episodes within the first 40 days after transplant, the final episode necessitating nephrectomy. The saralasin acetate infusion test and plasma renin activity (as measured by radioimmunoassay of angiotensin I) were used as functional tests of the renin-angiotensin axis. Biopsy specimens of the allograft one hour after implantation and sections of the nephrectomy specimen were fixed and stained with hematoxylin-eosin for structural analysis. On three separate dates, during the final rejection episode, saralasin acetate infusion of up to 20 micrograms/kg/min failed to lower BP significantly. The final two trials were preceded by furosemide administration the previous day to reduce fluid volume. Plasma renin activity was low on all three dates. On nephrectomy, the allograft was noted grossly to be infarcted. Histologic examination revealed cortical necrosis, markedly narrowed or occluded intrarenal vessels, and extremely narrowed large vessels within the renal pelvis. The allograft renal artery was thickened and narrowed. From our structural and functional analysis we conclude that (1) hypertension, in this case, was probably volume dependent and was clearly renin independent; and (2) the low renin levels are explainable on the basis of extensive vascular occlusion producing renal infarction and resulting in a kidney incapable of producing significant amounts of renin (autonephrectomy).

Adult↗
PubMed1984

Bioconversion and macromolecular binding of 2-amino-4-(5-nitro-2-furyl)thiazole by cultured rat urothelial cells.

Bioconversion and binding of 2-amino-4-(5-nitro-2-furyl)-thiazole (ANFT) were examined using cultured rat bladder epithelial cells from weanling male F344 rats. Bladder cells were obtained in large quantities from outgrowths of dissected explants which were grown on collagen gels. Metabolic potential of rat urothelial cells to activate ANFT was evaluated by incubating primary culture cells with [2-14C]ANFT for 48 hr. Metabolites were subsequently analyzed by chromatographic and spectroscopic methods. Thin-layer chromatography of the ethyl acetate:diethyl ether (1:1, v/v) extract of the culture medium revealed two regions of radioactivity with Rf values of 0.12 and 0.60, the former corresponding to ANFT and the latter to one of its metabolites. High-pressure liquid chromatography of the solvent extract revealed two major peaks, with retention times of about 4 and 9 min, corresponding with the metabolite and ANFT, respectively. Low-resolution mass spectrum of the isolated metabolite showed a molecular ion at m/e 181. The metabolite was identified as 1-[4-(2-aminothiazolyl)]-3-cyano-1-propanone based on its chromatographic and spectral characteristics in comparison with the synthetic compound. About 24% of the recovered radioactivity from the culture medium was extractable into the organic phase, a majority of which was identified as 1-[4-(2-aminothiazolyl)]-3-cyano-1-propanone. Analysis of binding to proteins and nucleic acids prepared following exposure of [2-14C]ANFT revealed a 15- and 9-fold greater amount of binding, respectively, in cultures incubated with bladder cells than their corresponding heat-inactivated controls. Furthermore, homogenates of cultured bladder cells reduced ANFT on anaerobic incubation with reduced nicotinamide adenine dinucleotide phosphate to generate 1-[4-(2-aminothiazolyl)]-3-cyano-1-propanone. On reduction of [2-14C]ANFT with rat bladder or liver homogenates, about 23 and 11%, respectively, of the initial amounts of radioactivity were bound to the trichloracetic acid-insoluble fraction. These data demonstrate that rat bladder cells possess the metabolic capability to reduce ANFT and to generate reactive intermediate(s) that bind to cellular macromolecules.

Animals↗
PubMed1983

Hypertension and cardiovascular hypertrophy during chronic catecholamine infusion in rats.

Chronic continuous infusion of norepinephrine (NE) or epinephrine (Epi) subcutaneously in rats resulted in rapid elevation of systolic blood pressure (SBP) by 40 mm Hg. Pressure remained high for the duration of the infusion but rapidly returned to control levels after its termination. Pronounced hypertrophy of the thoracic aorta, abdominal aorta and heart was evident within 2 days of the initiation of NE infusion and a plateau was attained by 5 days of infusion. The activity of tissue ornithine decarboxylase (ODC), the rate limiting enzyme in polyamine biosynthesis, was elevated preceeding the onset of tissue hypertrophy, and returned to control levels coincidentally with the cessation of accelerated tissue growth. It is concluded that high blood pressure in this animal model of hypertension is dependent upon the continued presence of exogenous catecholamine, and that pronounced cardiovascular hypertrophy per se is not sufficient to maintain the hypertension. The elevation and decline of vascular ODC activity is consistent with reports that in other tissues an elevation of ODC activity is an obligatory early event in hypertrophy.

Animals↗
PubMed1983

Growth and characterization of normal human urothelium in vitro.

A method for initiating rapidly growing cultures of normal human transitional cells from ureter and embryonic bladder specimens has been developed and quantified. A new microdissection technique was used to nonenzymatically separate the urothelium. The use of enriched medium containing 10 micrograms/ml insulin, 5 micrograms/ml transferrin, and 1 microgram/ml hydrocortisone resulted in improved growth. The use of thin collagen gel substrates (0.6 ml/60 mm petri dish) resulted in 97% attachment of explants compared to 77% attachment on plastic. Explants grown on thicker collagen (2 ml/60 mm petri dish) showed, in addition to better attachment, enhanced growth of cells as determined both by measurements of colony size and cell density. Cultures of transitional cells that were initiated using explants could be passed three to five times using 0.1% EDTA for dispersion. Autoradiography of [3H]thymidine-labeled cells showed an initial phase of rapid cell division in primary explant cultures and restimulation of cell division in passaged cultures. Transmission electron microscopy showed that the cells growing out from the explants were continuous with the stratified urothelium maintained in the original explant. Stratification of transitional cells occurred in cultures of both ureter and embryonic bladder cells. Surface cells were joined near their apices by junctional complexes. Desmosomes and Golgi vesicles were present in all cells. Passage in culture did not alter the morphological characteristics of cells.

Cell Division↗
PubMed1983

Fibronectin in evolution: presence in invertebrates and isolation from Microciona prolifera.

Fibronectin is found in the tissues of a series of vertebrates and invertebrates which suggests its appearance with the simplest multicellular organisms. Fibronectin is specifically localized on the surface and on the substrate in the immediate vicinity of some, but not all, dissociated Microciona prolifera cells, suggesting that the expression of fibronectin in this organism might be dependent on cell type and/or developmental stage. Fibronectin has been partially purified and characterized from intact Microciona prolifera tissue on the basis of its immunological and biochemical properties.

Animals↗
PubMed1983

Plasma renin activity during infusion of epinephrine into the celiac and superior mesenteric arteries in dogs.

Previous experiments have demonstrated that increments of circulating epinephrine concentration within the physiological range elevate PRA and that this effect apparently is mediated by extrarenal beta-adrenoceptors. The present experiments were designed to test the possibility that the receptors mediating the PRA response to epinephrine are located in the splanchnic region. Accordingly, adult dogs were anesthetized, and catheters were placed for recording blood pressure, withdrawal of blood samples, and collection of urine. Infusion catheters were placed in a femoral vein and in the celiac and superior mesenteric arteries. After a control period, epinephrine was infused for 45 min at a total rate of 25 ng kg-1 min-1 either iv or directly into the celiac and superior mesenteric arteries (12.5 ng kg-1 min-1 into each artery simultaneously). Renal perfusion pressure was kept at the control level during the infusion period by means of an adjustable suprarenal aortic clamp. PRA rose from a mean control plus recovery value of 4.5 +/- 0.9 ng ml-1 h-1 to 8.7 +/- 0.7 ng ml-1 h-1 during iv epinephrine infusion. In contrast, PRA remained unchanged (3.9 +/- 0.8 vs. 4.3 +/- 1.1 ng ml-1 h-1) in response to infusion of epinephrine directly into the celiac and superior mesenteric arteries. The data indicate that the receptors mediating epinephrine-induced increases in PRA are not located in organs perfused by the celiac and superior mesenteric arteries.

Animals↗
PubMed1983

Evidence that norepinephrine and epinephrine systems mediate the stimulatory effects of ovarian hormones on luteinizing hormone and luteinizing hormone-releasing hormone.

Results from previous investigations have suggested an important role for central epinephrine (EPI) systems in mediating the stimulatory effects of ovarian hormones on LH release in ovariectomized female rats. The purpose of these experiments was 1) to test whether selective inhibition of EPI synthesis blocks the sequential accumulation and decline of LHRH concentrations in the median eminence that precedes the ovarian hormone-induced LH surge and 2) to test whether the stimulatory ovarian hormone regimen enhances the activity of EPI systems in the hypothalamus. Ovariectomized rats were treated with estradiol, followed 2 days later by progesterone. Animals were treated before progesterone administration with saline, one of the EPI synthesis inhibitors [SK&F 64139 (2,3-dichloro-tetrahydroisoquinoline HCl) or LY 78335 (dichloro-alpha-methylbenzylamine)], or the dopamine-beta-hydroxylase inhibitor FLA-63 (bis-4-methyl-1-homopiperazinyl thiocarbonyl disulfide), which inhibits NE and EPI synthesis. The catecholamine synthesis inhibitors blocked or delayed the afternoon LH surge. FLA-63 completely prevented the accumulation of LHRH in the median eminence that preceded the rise in LH release. However, selective EPI synthesis inhibition with SK&F 64139 only partially prevented this increase in LHRH. A second EPI synthesis inhibitor, LY 78335, delayed both the LH surge and the rise in LHRH. In a second experiment, the administration of estradiol and progesterone to ovariectomized rats increased the alpha-methyltyrosine-induced depletion of hypothalamic EPI, suggesting increased activity in this system during the LH surge. Further experiments localized this effect to the medial basal hypothalamus. The depletion of both NE and EPI after synthesis inhibition was also enhanced during an earlier period, approximating the time of LHRH accumulation. These results suggest that the ovarian hormones activate both NE and EPI systems to stimulate the early afternoon rise of LHRH in the median eminence and to induce the subsequent LH surge.

Animals↗
PubMed1983

Acute effects of estradiol on circulating luteinizing hormone and prolactin concentrations and on serotonin turnover in individual brain nuclei.

Two experiments tested whether serotonergic neurons participate in the acute feedback effects of estradiol on LH and PRL secretion. In the first study, ovariectomized female rats received oil vehicle or estradiol benzoate and were killed 3 h later. The turnover of serotonin [5-hydroxytryptamine (5-HT)] in microdissected brain nuclei was assessed from its accumulation after monoamine oxidase inhibition. Estradiol treatment produced a gradual rise in PRL and a decline in LH, and potentiated the accumulation of 5-HT in the medial preoptic, ventromedial, and cortical amygdaloid nuclei, suggesting increased turnover. Concentrations of the metabolite, 5-hydroxyindole acetic acid, were also elevated in these areas. 5-HT turnover was unaffected by estradiol in the interstitial nucleus of the stria terminalis, periventricular, dorsomedial, or lateral amygdaloid nuclei. The second experiment tested whether localized 5-HT depletions in these estradiol-activated nuclei blocked the acute effects of the steroid on LH or PRL. Stereotaxic microinjections of the 5-HT neurotoxin, 5,7, dihydroxytryptamine were made into the preoptic area, cortical amygdala, or medial basal hypothalamus in ovariectomized rats, pretreated with desmethylimipramine. Such treatment reduced 5-HT, without affecting catecholamines, in the targeted structures. Localized 5-HT depletion in the preoptic area and amygdala blunted the elevation of PRL, but not the decline of LH, after estradiol. 5-HT depletion in the medial basal hypothalamus elevated, whereas 5-HT depletion in the medial preoptic area lowered, resting levels of LH. These results suggest that: 1) estradiol may acutely increase PRL secretion by activating serotonergic projections to the medial preoptic and cortical amygdaloid nuclei, and 2) serotonergic neurons innervating the preoptic area stimulate LH release, whereas serotonergic systems in the medial basal hypothalamus inhibit LH release.

5,7-Dihydroxytryptamine↗
PubMed1983

Paradoxical elevation of sympathetic activity during catecholamine infusion in rats.

Chronic infusion of norepinephrine (NE) or epinephrine in rats by an Alzet osmotic minipump (0.1 mg/kg/hr s.c.) caused a 40 mm Hg increase in systolic blood pressure with no change in heart rate. The administration of chlorisondamine or bretylium, drugs which inhibit sympathetic neuronal function by blocking ganglia and by inhibiting release of neuronal NE, respectively, decreased systolic blood pressure to the same level in NE-infused and vehicle-infused rats whereas heart rate increased only in NE-infused animals. Infusion of NE or epinephrine resulted in a marked elevation in the plasma level of the infused amine and a smaller elevation of its counterpart. Chlorisondamine caused a 30 to 70% reduction in plasma levels of NE and epinephrine during the infusion of these catecholamines. Acute infusion of NE at a rate which caused a slow pressor response was accompanied by an elevation of impulse frequency in the preganglionic cervical sympathetic nerve. In contrast, a faster rate of NE infusion which produced a more rapid pressor response was accompanied by the classical decrease in impulse frequency. These studies demonstrate that the maintenance of elevated blood pressure during catecholamine infusion in rats is dependent upon a paradoxical increase in the activity of the sympathetic nervous system.

Animals↗
PubMed1982

Serotonin turnover in individual brain nuclei: evaluation of three methods using liquid chromatography with electrochemical detection.

Liquid chromatography with electrochemical detection and brain microdissection techniques were used to evaluate three methods of studying serotonin turnover in 10 individual brain nuclei. The increase in serotonin (5-HT) and decline in 5-hydroxyindole acetic acid (5-HIAA) after administration of the monoamine oxidase inhibitor, pargyline, as well as the accumulation of 5-hydroxytryptophan (5-HTP) after the L-amino acid decarboxylase inhibitor, m-hydroxybenzylhydrazine, were measured. Serotonin accumulation and 5-HIAA decline could be detected in the n. caudatus, globus pallidus, cortical amygdala, n. interstitialis striae terminalis, n. preopticus medialis, and n. dorsomedialis. Only serotonin accumulation could be accurately assessed in the n. ventromedialis, n. arcuatus, and median eminence. The pattern of increase of serotonin after pargyline varied in different nuclei. There was a linear increase of serotonin over 90 minutes in the caudate, globus pallidus, and ventromedial nucleus and over 60 minutes in the n. preopticus medialis, and cortical amygdala. This contrasted with a maximal increase at 30 minutes in the other nuclei. However, 5-HIAA decline tended to be greatest after 30 minutes in most nuclei. Increases in 5-HTP concentrations after decarboxylase inhibition were not reliably detected in these areas. These results indicate that two nonsteady state methods may be used to evaluate changes in serotonin turnover in selected individual, nonpooled hypothalamic and forebrain nuclei.

5-Hydroxytryptophan↗
PubMed1982

Regulation of episodic growth hormone secretion by the central epinephrine system. Studies in the chronically cannulated rat.

Catecholamines are postulated to regulate growth hormone (GH) secretion by their influence on the release of two hypothalamic substances, somatostatin, which inhibits GH release, and GH-releasing factor, as yet unidentified. Extensive pharmacologic studies in man and animals indicate a stimulatory effect of central norepinephrine and dopamine on GH, but the function of epiphephrine (EPI) is uncertain. Furthermore, many of the agents used to study the role of catecholamines in GH regulation are not selective in that they affect adrenergic as well as nor-adrenergic and/or dopaminergic neurotransmission. In the present investigation, central nervous system (CNS) EPI biosynthesis was selectively interrupted with the specific norepinephrine N-methyltransferase inhibitors, SK & F 64139 (Smith, Kline & French Laboratories) and LY 78335, (Eli Lilly & Co. Research Laboratories) and the effects of central EPI depletion on episodic GH secretion in the chronically cannulated rat model were determined. Inhibition of CNS EPI synthesis with SK & F 64139 caused complete suppression of episodic GH secretion and concomitantly reduced the EPI level in the hypothalamus without affecting dopamine or norepinephrine. Administration of LY 78335 produced similar effects on pulsatile GH. Morphine-induced, but not clonidine-induced, GH release also was blocked by SK & F 64139. These results indicate that (a) the central EPI system has a major stimulatory function in episodic GH release, (b) morphine-induced GH release is mediated by the central EPI system, and (c) clonidine stimulates GH release by activation of postsynaptic alpha-adrenergic receptors. Drugs that affect CNS adrenergic systems have a potential role in the diagnosis and treatment of disorders of GH secretion.

Amines↗
PubMed1982

Plasma renin activity during infusion of epinephrine into the carotid and vertebral arteries of anesthetized dogs.

Previous experiments have demonstrated that increments of epinephrine concentration within the physiological range elevate PRA when epinephrine is infused iv but not when it is infused directly into the renal artery. The present experiments examined whether an elevation of the circulating epinephrine concentration to the head could account for this elevation of PRA by epinephrine. Anesthetized dogs were surgically prepared for blood sampling and blood pressure recording and for the infusion of epinephrine into either a femoral vein (iv) or the carotid and vertebral arteries. After a control period, epinephrine was infused for 45 min at a total rate of 25 ng kg-1 min-1 either iv or into the head vasculature (3.5 ng kg-1 min-1 into each vertebral artery and 9 ng kg-1 min-1 into each carotid artery). PRA (in nanograms per ml h-1) rose from 1.8 +/- 0.5 to 5.9 +/- 1.2 (mean +/- SE) during iv epinephrine infusion. PRA rose similarly (from 1.5 +/- 0.4 to 4.8 +/- 1.8) during epinephrine infusion to the head. The arterial blood epinephrine concentration rose similarly in response to iv and head epinephrine infusions. Furthermore, the changes in hematocrit, heart rate, blood pressure, and plasma potassium concentration were identical regardless of the route of epinephrine infusion. In separate experiments, a smaller infusion of epinephrine infusion. In separate experiments, a smaller infusion of epinephrine directly into the head vasculature at a total rate of 2.5 ng kg-1 min-1 (0.35 ng kg-1 min-1 into each vertebral artery and 0.9 ng kg-1 min-1 into each carotid artery) was without effect on PRA. The data indicate that 1) epinephrine is apparently neither taken up nor degraded by the microcirculation of the head, and 2) the receptors mediating the stimulatory effect of epinephrine on PRA are not located in regions supplied by the carotid and vertebral arteries.

Animals↗
PubMed1982

Vibration effects on three measures of relaxation.

The effect of vibrotactile stimulation on relaxation as measured by EMG recording of the frontalis and trapezius muscles and by subjective report was assessed. It was predicted that low-frequency vibrotactile stimulation (less than 70 Hz) would facilitate muscle relaxation when measured by both EMG frontalis and trapezius recordings and by subjective report. The participants (8 male and 8 female) were randomly assigned to split-plot, before/after design consisting of four between-subjects treatments and one within-subjects treatment (pre- and post-treatment). The between-subjects treatments were footrest vibration, backrest vibration, footrest-backrest vibration combined, and control. The within-subjects treatment included pre- and post-treatment levels. Results of repeated-measures analyses of variance on each set of data yielded a significant change from pre- to posttreatment condition on all EMG and subjective report measures of muscle tension except the control. The utility of using EMG as a measure of relaxation is discussed.

Adult↗