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Biomedical subjects

M Morris

Publications and source records attributed to M Morris.

At least 397 records · Page 22Linked to original sources

Biochemical and immunochemical studies of supraoptic and paraventricular cultures.

A tissue culture model was established for the study of hypothalamic peptide synthesis and secretion. Microdissected explants of the paraventricular and supraoptic regions from Sprague-Dawley rats (neonates or young rats) were maintained in culture for up to 3 weeks. Studies were performed to evaluate vasopressin and oxytocin content (medium and tissue levels), immunocytochemical localization, and biosynthetic activity. Immunocytochemical staining for oxytocin, neurophysin, and neuron-specific enolase showed positive neurons in both the paraventricular and supraoptic cultures. In many cases, the neurons were large (30-40 microns) and bipolar, resembling the classic magnocellular neuron. Measurement of tissue and medium content showed the continued presence of vasopressin and oxytocin in the cultured explants. Even after 3 weeks, there were significant amounts of vasopressin present. Biosynthesis was evaluated by determining the incorporation of 35S-labeled cystine or cysteine into proteins and peptides. The medium and tissue extracts were separated by reverse-phase high-performance liquid chromatography. Results showed that most of the labeled peptides were released into the medium rather than stored. There were two labeled peaks in the medium, which chromatographically resembled native vasopressin and oxytocin. Treatment with a protein synthesis inhibitor, either puromycin or cycloheximide, resulted in a decrease in labeled peptides. A comparison of 35S-labeled cystine and cysteine showed that the latter was the label of choice, with significantly greater incorporation.

Animals↗

A reduction of central peptidergic responses in the spontaneously hypertensive rat.

The effect of intraventricular perfusion with hypertonic saline (HS) or angiotensin II (ANG II) on cerebrospinal fluid (CSF) vasopressin (AVP), blood pressure and heart rate was determined in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. There was a marked reduction in the central peptidergic response in the SHR. Pretreatment with the AVP (V1) antagonist abolished the pressor response to intraventricular HS in the WKY rats, but not in the SHR.

Angiotensin II↗

Endometrial carcinoma presenting with ascites.

Three examples of endometrial carcinoma presenting with ascites are reported. The patients were in the eighth decade, had no vaginal bleeding, and were considered to have ovarian cancer preoperatively. Laparotomy revealed gross omental tumor and normal appearing ovaries. The endometrial cancers were grossly undetected and were uniformly noninvasive of the myometrium. They projected into the uterine cavity, two in polyps, and one covering a submucous leiomyoma. The fallopian tubes were the most likely route of spread to the abdominal cavity.

Adenocarcinoma↗

Determination of the parameters of self-association by direct fitting of the omega function.

Nonlinear regression is used to fit the omega function vs. protein concentration curves (first described by B.K. Milthorpe, P.D. Jeffrey and L.W. Nichol, Biophys. Chem. 3 (1975) 169) obtained from sedimentation equilibrium experiments on self-associating macromolecules. Nonlinear regression allows the direct fit of these curves with discrete or indefinite self-association reaction models in order to obtain values for the equilibrium constants and second virial coefficient. The method is independent of the choice of reference concentration and avoids the original method of extrapolating an omega function curve to zero concentration and then using the extrapolated value to construct a monomer activity curve used for analysis. This extrapolation can become very difficult for mild to strong self-associations where incorrectly extrapolated values lead to systematic error in the monomer activity curves. The method is applied to results from a mild, indefinite self-association, exemplified by the self-association of human spectrin, and to computer-simulated data of weak, mild and strong, indefinite self-associations.

Erythrocytes↗

Colposcopic screening of women with atypical Papanicolaou smears.

A retrospective study was done on 575 patients with atypical Papanicolaou smears obtained during a ten-year period (1974-83) at Bellevue Hospital-New York University Medical Center. The smears were classified into three categories. The first consisted of 463 patients (81%) with inflammatory atypia specifically treated for Trichomonas, Monilia, Chlamydia, Gardnerella and atrophic vaginitis. Of them, 162 patients (35% of the group) had persistent inflammatory atypia 90 days after the beginning of therapy and were subjected to colposcopic examination. The second group consisted of 86 patients (15%) with squamous atypia. That group underwent colposcopic examination. The third group, 26 patients (4%), had endocervical atypia and underwent colposcopy and endocervical curettage. Overall, of 162 patients with persistent inflammatory atypia, 36 (22%) were found to have cervical intraepithelial neoplasia (CIN); of 86 with squamous atypia, 60 (70%) had CIN; and of 26 with endocervical atypia, 15 (58%) had CIN. Fifty-eight (28%) of all the patients with CIN had lesions of severity greater than CIN 1. It appears that all patients with persistent inflammation or squamous or endocervical atypia would benefit from colposcopic screening.

Biopsy↗

GABA agonists inhibit central sodium-induced vasopressin-dependent increases in arterial pressure.

Previous studies have demonstrated that intraventricular (i.v.t.) administration of low doses of GABA agonists reduced the central pressor effects of cerebrospinal fluid (CSF) made hypertonic with sodium (Na). The following studies were designed to determine if GABA agonists acted to decrease the pressor response of Na through inhibition of the vasopressin-dependent pressor component. Following pretreatment with vascular vasopressin antagonist, the pressor response of i.v.t. administered Na was reduced approximately 60%. Hypophysectomy produced a similar reduction in the pressor response elicited by hypertonic CSF. These results indicate that vasopressin contributed to approximately 60% of the pressor response of Na. In order to generate a vasopressin-dependent pressor response, the sympathetic nervous system was eliminated with ganglionic blockade by chlorisondamine. The increase in arterial pressure produced by i.v.t. injection of hypertonic CSF was augmented after ganglionic blockade compared to untreated rats. The augmented pressor effect of i.v.t. administered Na was markedly reduced by the vascular vasopressin antagonist or by hypophysectomy. Therefore, the pressor effect of Na after ganglionic blockade was caused almost entirely by the pressor actions of arginine-vasopressin (AVP). This AVP-dependent pressor effect of i.v.t. injected Na in rats subjected to ganglionic blockade was reduced by pretreatment with 100 micrograms of GABA or 50 ng of the GABA agonist muscimol. These doses of GABA and muscimol have previously been shown to reduce the pressor response of i.v.t. administered Na in untreated rats. Thus, pretreatment with low doses of GABA agonists reduced the pressor effect of Na in part through inhibition of the vasopressin component of the pressor response. GABA pretreatment also antagonized the increase in plasma AVP levels produced by i.v.t. administered hypertonic CSF.

Animals↗

A reappraisal of the self-association of human spectrin.

The self-association behaviour of human spectrin has been re-examined through a study of sedimentation equilibrium, sedimentation velocity and gel electrophoresis. In all cases we find evidence for oligomers of spectrin larger than the tetramer, even at low concentration. The data are not consistent with a simple dimer-tetramer model, but instead indicate an open, or indefinite, pattern of association. Although a good fit to the data can be achieved with the isodesmic reaction model, with an equilibrium constant in agreement with the value previously determined for the dimer-tetramer reaction, there is other evidence suggesting that the actual association scheme may be somewhat more complex.

Electrophoresis, Polyacrylamide Gel↗

Cortisol infusion blocks adrenocorticotropic hormone but not vasopressin responses to hypotension in fetal lambs.

In eight experiments in which a paired crossover design was used, we studied the ability of physiologic levels of cortisol to block adrenocorticotropic hormone (ACTH) and vasopressin responses to hypotension in fetal lambs. On different days, each fetus received a 4-hour infusion of cortisol or ethanol-saline solution vehicle, and then hypotension was induced with nitroprusside. Mean levels of ACTH before manipulation were 20 +/- 10 pg/ml and 18 +/- pg/ml in the saline solution- and cortisol-treated animals, respectively. Mean values of ACTH increased significantly to 70, 88, and 127 pg/ml at 2.5, 5, and 10 minutes of hypotension after pretreatment with saline solution. Cortisol pretreatment abolished the fetal ACTH response to hypotension. Mean levels of vasopressin during the control period were similar in the two groups of animals (5.7 +/- 1.5 pg/ml versus 5.9 +/- 1.3 pg/ml) and rose to comparable levels (69.4 +/- 15.6 pg/ml versus 65.2 +/- 7.7 pg/ml) during hypotension. Thus, increases in plasma cortisol levels within a physiologic range can suppress hypotension-induced ACTH but not vasopressin release in the fetus.

Adrenocorticotropic Hormone↗

MOH rules--OK?

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Community Health Nursing↗

Vasopressin and urine flow rate responses to stress in conscious dogs.

Behavioral stress increases arterial pressure while decreasing urine flow rate; the urine flow rate response can be abolished by surgical renal denervation. In this study, the effects of infusion of alpha-adrenoceptor antagonists (intravenous phenoxybenzamine or prazosin) on the antidiuretic and plasma vasopressin responses to stress were examined. Without alpha-adrenoceptor blockade, 20 min of stress increased arterial pressure and decreased urine flow rate, but no change in urine osmolality or plasma vasopressin concentration occurred. Arterial pressure and urine flow rate returned to base-line level during a 20-min recovery period. With alpha-adrenoceptor blockade, which prevented the arterial pressure response to stress, urine flow rate still decreased during stress, but urine osmolality and plasma vasopressin concentration increased. The decrease in urine flow rate and increase in urine osmolality and plasma vasopressin concentration persisted into the first 20-min recovery period but returned to base-line level during a second 20-min recovery period. We conclude that the antidiuretic response to behavioral stress in conscious dogs with saline infusion alone is not mediated via a change in vasopressin release. In contrast, the antidiuretic response to behavioral stress with alpha-adrenoceptor antagonist infusion may be mediated via an increased release of vasopressin.

Animals↗

Osmotic mechanisms regulating cerebrospinal fluid vasopressin and oxytocin in the conscious rat.

The effect of intraventricular and intravenous (i.v.) hypertonic saline on plasma and perfusate arginine vasopressin (AVP) and oxytocin (OT) levels was determined. A push-pull technique was used to sample third ventricular cerebrospinal fluid (CSF) in the conscious unrestrained rat. Intraventricular perfusion of hypertonic saline caused a 6.1- and 4.2-fold increase in perfusate levels of AVP and OT. Plasma levels with the same stimulus increased 3.5-fold for AVP and 3.4-fold for OT. Peak levels of the peptides occurred at 30 and 60 min in the CSF perfusate and plasma, respectively. Thus, the central peptide response occurred earlier and was of a greater magnitude than the systemic one. Intravenous hypertonic saline administration caused a rapid (15 min) increase in plasma AVP and OT, changes of 12.6- and 22.9-fold. Perfusate AVP did not change with i.v. hypertonic saline while OT was increased 10-fold. Two types of recovery experiments were performed (1) in which the rate of disappearance of 125I-labeled peptides from CSF was determined and (2) in which total body water was labeled with 3H2O and the amount of dilution determined. Both techniques showed that recovery of endogenous CSF in the push-pull perfusate was approximately 15%. Thus, the perfusate peptide levels represent an underestimation of in vivo secretion. Osmotic stimuli elicit specific changes in the third ventricular levels of AVP and OT. The differential response in the two hormones to i.v. hypertonic saline shows a uniqueness in the mechanisms controlling the central secretion of AVP and OT.

Animals↗

GABA agonists inhibit the vasopressin-dependent pressor effects of central angiotensin II.

Previous studies have demonstrated that intraventricular (IVT) administration of low doses of gamma-aminobutyric acid (GABA) agonists reduced the pressor effects of centrally injected angiotensin II (AII). The following studies were designed to determine if GABA agonists acted to inhibit the pressor response of AII through blockade of the vasopressin-dependent pressor component. Following pretreatment with a vascular vasopressin antagonist, the pressor response of IVT administered AII was reduced approximately 50%. Hypophysectomy produced a similar reduction in this pressor response. These results suggested that vasopressin contributed to one-half of the pressor response of AII. In order to generate a vasopressin-dependent response, the sympathetic nervous system was eliminated with ganglionic blockade by chlorisondamine. The increase in arterial pressure produced by IVT injected AII after ganglionic blockade was augmented compared to untreated rats. This potentiated pressor effect of IVT administered AII after chlorisondamine treatment was markedly reduced by a vascular vasopressin antagonist or by hypophysectomy. Therefore, the pressor effect of AII after ganglionic blockade was caused principally by the pressor actions of arginine-vasopressin (AVP). This AVP-dependent pressor effect of IVT injected AII was reduced by pretreatment with 100 micrograms of GABA or 50 ng of the GABA agonist muscimol. These doses of GABA and muscimol have previously been shown to reduce the pressor response of IVT administered AII by approximately 60% in untreated rats. Thus, pretreatment with low doses of GABA agonists reduced the pressor effect of IVT injected AII in part by inhibiting the vasopressin component of this response.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

Vasopressin is important for restoring cardiovascular homeostasis in fetal lambs subjected to hemorrhage.

To determine if the posterior pituitary hormone vasopressin is important for maintaining fetal cardiovascular homeostasis during hypovolemic stress, in seven chronically catheterized fetal lambs we induced hemorrhage of 20% of estimated blood volume in the presence and in the absence of a potent antagonist to the pressor effects of vasopressin. The study was a paired crossover design with at least 48 hours separating experiments in the same animal. Injection of the vasopressin antagonist did not alter basal fetal heart rate or arterial blood pressure, but hemorrhage of 2% of estimated fetal blood volume per minute for 10 minutes produced a greater fall in blood pressure (13 +/- 2 versus 10 +/- 2 torr, p less than 0.05) when the blocker was present than when it was absent. Arterial blood pressure remained below control levels longer following hemorrhage when the fetuses were pretreated with the antagonist (49.7 +/- 6 versus 26.6 +/- 6 minutes, p less than 0.01), and the integrated fall in arterial blood pressure with hemorrhage was greatest (283 +/- 53 versus 169 +/- 57 mm Hg . min p less than 0.01) when the blocker was used. The fall in heart rate following hemorrhage was similar with and without blocker pretreatment. These results indicate that vasopressin plays a physiologic role in blood pressure regulation in fetal lambs during periods of hypovolemia.

Animals↗

Comparison of timegadine and naproxen in rheumatoid arthritis. A placebo controlled trial.

A double blind, cross-over design was used to compare the acute effects of timegadine, naproxen and placebo in rheumatoid arthritis. Timegadine appeared to be more effective than naproxen in those variables related to disease activity although there were no statistically significant differences (apart from morning stiffness) where variables were examined individually. There was a tendency to a rise in alkaline phosphatase, and possibly gamma glutamyl transpeptidase, during the 2-week timegadine treatment period. No other biochemical or haematological abnormality was observed.

Adult↗

Hypothalamic catecholamine biosynthesis and neuropeptides.

In conclusion, both steady state and non-steady state methods for investigating the turnover of central catecholamines can provide valuable information regarding the central control of neuroendocrine function. The system described here, utilizing HPLC with electrochemical detection, offers a relatively easy and reliable method for determining steady state catecholamine biosynthesis in the hypothalamus and other brain areas.

Animals↗

Methods for investigating peptide precursors in the hypothalamus.

In conclusion, as in the aminergic nervous system, the hypothalamic neuropeptides "turn over" at a rate sufficient to maintain a "steady state" concentration within the hypothalamus. However, unlike catecholamine-secreting neurons, the brain peptides are synthesized and secreted by a much more circuitous mechanism, involving ribosomal biosynthesis as larger prohormones, axonal transport to the site of secretion, and enzymic processing to the biologically active hormones. The methods described here, including in vitro incubation and high-performance size-exclusion and reverse-phase chromatography, have been found to be useful for examining and comparing the rate and mechanism of biosynthesis of several hypothalamic neuropeptides.

Amino Acids↗

The protective effect of inhaled chlorpheniramine and atropine on bronchoconstriction stimulated by airway cooling.

We examined the role of histamine release and reflex bronchoconstriction in the bronchoconstriction stimulated by airway cooling. In 8 asthmatic subjects, dose-response curves were determined to isocapnic hyperventilation of cold air 30 min after inhalation of chlorpheniramine maleate (18 mg nebulized during tidal breathing), 2 doses of atropine sulphate (3 mg and 18 mg nebulized), or placebo. Treatments were given on separate days, in random order and under double-blind conditions. The bronchial antihistamine and anticholinergic actions of chlorpheniramine were determined by the effect on histamine and methacholine dose-response curves on another 4 days. Chlorpheniramine was selective as an antagonist against histamine; it increased the mean provocation concentration of histamine to reduce the FEV1 by 20% (PC20) 14.2-fold but increased the mean PC20 methacholine only 1.85-fold. Atropine in the 3-mg dose, previously shown to increase the PC20 methacholine at least 100-fold, had no effect on heart rate or saliva output in contrast to 18 mg, which significantly reduced saliva output and increased heart rate. Chlorpheniramine caused no bronchodilation and a small 1.28-fold increase in the amount of respiratory heat exchange needed to reduce the FEV1 by 10% (PD10RHE). Atropine caused maximal bronchodilation after 3 mg and a dose-dependent increase in PD10RHE (1.16-fold increase after 3 mg and 1.32-fold increase after 18 mg atropine). The effect of chlorpheniramine and atropine 18 mg on PD10RHE was not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗