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T McDonald

Publications and source records attributed to T McDonald.

At least 73 records · Page 4Linked to original sources
PubMed1990

Association of androgen binding sites with the endoplasmic reticulum of rat ventral prostate.

Microsomes from ventral prostate of 24-h castrated rats contain a single set of tissue-specific high-affinity, low-capacity androgen binding sites. These sites are indigenous to the endoplasmic reticulum, as shown by purification procedures associated with marker enzymes and electron microscopic analyses. When prostatic microsomal membranes are separated from plasma membranes using the nuclear or the mitochondrial pellets as the source of fractionation in sucrose gradients, the androgen binding activity is selectively associated with fractions rich in rough endoplasmic reticulum and ribosomes. Eighty-four percent of the total content of Na+/K+ adenosine triphosphatase (ATPase) and only 27% of the total binding capacity were concentrated in fractions rich in smooth-surfaced vesicular membranes, when nuclear suspensions constituted the membrane source. In contrast, the region of the same gradient when enriched in rough endoplasmic reticulum and deficient in plasma membrane content contained 73% of the androgen-binding capacity and only 14% of the ATPase. For fractions collected using mitochondrial suspensions as starting material, the ratio (total glucose-6-phosphatase/total binding capacity) was closer to 1.0 than similar ratios of ATPase/binding capacity, indicating co-sedimentation of binding sites with microsomal membranes and not with plasma membranes. Na+/K+ ATPase, but not 5' nucleotidase, is a valid plasma membrane marker for ventral prostate. Microsomal androgen receptors may constitute a new level of regulation of androgen action in target cells.

Androgens↗
PubMed1990

Prevalence of nonclassical steroid 21-hydroxylase deficiency based on a morning salivary 17-hydroxyprogesterone screening test: a small sample study.

Early morning salivary 17 alpha-hydroxyprogesterone (17-OHP) determination differentiates patients with non-classical 21-hydroxylase deficiency (NC21OHD) from those who are not affected. Using this test, we have conducted a trial screening study for NC21OHD and have compared the study results with previously reported figures for the frequency of this disorder. Testing was performed on 258 subjects recruited from among the medical students and employees of the New York Hospital-Cornell Medical Center. In 2 of the 249 admissible subjects, the 0700-0900 h salivary 17-OHP level was within the range for NC21OHD patients (0.72-6.7 nmol/L; n = 8). These 2 individuals were subsequently confirmed to be affected by ACTH testing. Of the subjects with morning salivary 17-OHP levels below the cut-off point of 0.72 nmol/L, 29 were recalled for ACTH testing and were confirmed to be unaffected. Prevalence of NC21OHD in the test population was determined according to ethnic group. Our study gives a prevalence by screening of 1.14% among caucasians, which agrees with values of 0.81% and 1.06% obtained by different analytical methods. Further, both affected subjects were Ashkenazi Jews, and the prevalence of 3.23% among study members from this group concurs with increased rates of 3.64% and 4.97% already reported. On the basis of a small population sample, screening so far confirms the claim that NC21OHD is the most common autosomal recessive human disorder. Using values from ACTH-proven unaffected subjects (n = 47) and NC21OHD patients (n = 10), we establish preliminary normative data for morning salivary 17-OHP levels of 0.172 nmol/L for unaffected subjects (95% confidence interval, 0.05-0.54 nmol/L) and 1.76 nmol/L for NC21OHD-affected subjects (95% confidence interval, 0.42-7.32 nmol/L).

17-alpha-Hydroxyprogesterone↗
PubMed1989

Dual action (stimulation, inhibition) of D600 on contractility and calcium channels in guinea-pig and cat heart cells.

1. We examined the effects of D600 (0.2-40 microM, generally 2 microM) on the following (i) developed tension in guinea-pig papillary muscles, (ii) calcium current (Ica) and tension in cat ventricular muscle strands, (iii) Ica in guinea-pig and cat ventricular myocytes, (iv) single Ca2+ channel currents carried by Ba2+ in cell-attached membrane patches of guinea-pig ventricular myocytes, and (v) Ba2+ currents through dihydropyridine (DHP)-binding sites (skeletal muscle) reconstituted into single functional Ca2+ channels in lipid bilayers. 2. In 27 of 140 preparations studied, D600 elicited a transient stimulation that preceded marked inhibition. The stimulation was normally of short duration (less than 5 min) and moderate strength (less than 50% increase). 3. D600 had no effect on the unit conductance of single cardiac Ca2+ channels. Stimulation was characterized by a decrease in the number of records with no openings (blanks) and an increase in the open-state probability of non-blanks (longer open times, shorter closed times). Inhibition began with an increase in the number of blanks and later included a curtailment of open times and a prolongation of closed times. The net effect after 9 min D600 was a 75% reduction in average current amplitude. 4. A similar pattern of changes in channel open and closed times produced enhancement and then depression of time-averaged open-state probability in single reconstituted channels. 5. Single Ca2+ channel current that was stimulated by adrenaline was only slightly depressed after 2 microM-D600 for 30 min. It may be that channel phosphorylation or Gs-protein activation following beta-receptor stimulation reduces channel affinity for D600. 6. Short-lived binding of D600 to a single inhibitory site may enhance association/activation of Gs-protein and thereby cause transient up-regulation prior to increased drug occupancy and inhibition. Alternatively, there may be separate stimulatory and inhibitory sites. One aspect of inhibition, the increased frequency of blanks, is attributed to a stabilization of the inactivated state; the other aspect, changes in fast kinetics, seems to require a different explanation.

Animals↗
PubMed1989

Neuropeptide cells and fibers in the hypothalamus and pituitary of the fetal sheep: comparison of oxytocin and arginine vasopressin.

Both oxytocin (OXY) and arginine vasopressin (AVP) enhance the effects of corticotropin-releasing factor on ACTH release by the pituitary. One of these, AVP, plays a role in the control of fluid balance and responses to hypoxemic stress in the fetal sheep. To determine the possibility that OXY also participates in fetal neuroendocrine events, OXY-containing neuronal structures must first be demonstrated within the fetal endocrine hypothalamus. OXY-immunoreactive elements were examined in fetal sheep hypothalami late in gestation and compared to AVP-containing structures using immunocytochemical procedures. Six fetal sheep ranging from 126 to 144 days gestational age were delivered via cesarian section from timed pregnant Rambouillet-Columbia ewes and killed by an overdose of anesthesia. The fetal head was perfused via bilateral carotid catheters and processed for immunocytochemical localization of OXY or AVP using the avidin-biotin complex procedure. At all fetal ages examined, OXY- and AVP-containing neurons were found within the paraventricular nuclei (PVN), supraoptic nuclei (SON) and accessory magnocellular hypothalamic nuclei. OXY-containing neurons were found principally in the SON and PVN. They were generally less numerous and less intensely stained than the AVP neurons. In the SON, they concentrated along the dorsal borders of the nucleus above the AVP neurons. In PVN, clusters of OXY cells were located along the dorsal and lateral borders of the nucleus surrounding the AVP neurons; in the periventricular division, they were intermingled with the AVP neurons. Small numbers of OXY axons were located in the external zone of the median eminence; whereas most OXY axons extended into the hypothalamo-neurohypophyseal tract and posterior lobe of the pituitary. A few of the OXY axons in the pituitary stalk were diverted to the pars intermedia. Likewise, some of the OXY fibers from the external zone of the median eminence entered the pars tuberalis but were rarely found in the distal lobe of the pituitary. In contrast, AVP axons richly innervated the external zone of the median eminence, and neural lobe. Like OXY, AVP axons from the median eminence and the pituitary stalk sent projections to the adenohypophysis. AVP fibers in the pars distalis frequently contacted corticotropes and were more numerous than OXY fibers in this region. These data provide anatomical evidence that OXY and AVP may directly regulate the fetal adenohypophysis. Of these two neuropeptides, AVP predominates anatomically.

Animals↗
PubMed1989

Injury induces increase of von Willebrand factor in rat endothelial cells.

This study examined the effects of injury on the content of von Willebrand factor (vWF) in rat aortic endothelium. Endothelial cells from normal, endotoxin-treated, and balloon-injured rats were stained with vWF antibodies and visualized using a biotinylated secondary antibody and avidin-tagged peroxidase. Endotoxin treatment and balloon injury caused a threefold increase in intracellular vWF, and immunoelectron microscopy showed the endoplasmic reticulum to stain heavily by the vWF antibody. Weibel-Palade bodies were not observed in all the cell profiles examined. The basement membrane of the endothelialized vessels showed no vWF staining; however, after endothelial denudation this matrix was clearly stained by the antibody. These results suggest that endothelial injury leads to an increased intracellular content of vWF that is localized primarily in the endoplasmic reticulum.

Animals↗
PubMed1989

Danazol-induced cholestasis.

A 39-yr-old female on high-dose Danazol presented with jaundice and pruritus. Danazol-induced cholestasis was suspected, and the drug was discontinued. A liver biopsy revealed panlobular cholestasis with portal and periportal inflammation. The cholestasis resolved completely in 8 wk. This is a rare case of Danazol-induced cholestasis and should be considered in the differential diagnosis of drug-induced liver injury.

Adult↗
PubMed1988

Metabolic changes in Alzheimer's disease.

Patients with Alzheimer's disease (AD) and matched controls fasted for 24 hours, and serial glucose, pyruvate, lactate, beta-hydroxybutyrate, acetoacetate, insulin, and glucagon levels were measured. Patients with AD showed a glucose insulin correlation pattern over the 24 hours that differed from the control group. These differences may be secondary to weight loss or to other metabolic or nutritional factors affecting the AD patients.

3-Hydroxybutyric Acid↗
PubMed1986

Proliferation of human peripheral blood lymphocytes induced by recombinant human interleukin 2: contribution of large granular lymphocytes and T lymphocytes.

Recombinant human interleukin 2 (rH IL-2) in the presence or absence of additional stimuli, was found to be able to induce and support the proliferation of human peripheral blood lymphocytes (PBLs). These proliferative effects were observed at low doses (less than or equal to 10 U/ml) of interleukin 2 (IL-2) only when additional signals (antigen, mitogen) were provided. However, higher doses (greater than or equal to 100 U/ml) of rH IL-2 significantly stimulated the proliferation of PBL even in the absence of exogenous lectin, antigen, or allogeneic serum. The subpopulation of lymphocytes most responsive to these higher doses of rH IL-2 was the large granular lymphocyte (LGL), the morphologic homologue of natural killer activity. After the separation of human PBLs on discontinuous Percoll gradients, cells from fraction 2 (greater than 90% LGLs) responded in a dose-dependent manner to rH IL-2 alone, whereas cells from fraction 6 (greater than 90% T cells) were only slightly responsive to rH IL-2 alone. A portion of the proliferation of cells from fraction 2 was dependent on the expression of the TAC receptor, because the prior removal of TAC-positive cells significantly reduced IL-2-induced lymphocyte proliferation. These results demonstrate that human LGL that have not been exogenously stimulated can proliferate in direct response to IL-2, and suggest that LGL are the major cellular phenotype in the proliferative response that has been observed clinically.

Cell Cycle↗
PubMed1986

Errors in measurements of CO2 with the use of drying agents.

To assess the errors in measurements of CO2 concentration that arise from the widespread use of drying agents in clinical and physiological studies, continuous measurements of CO2 concentration were made with an infra-red analyser before and after standard gas mixtures were passed through a tube containing one of several drying agents: calcium chloride; calcium sulphate (Drierite); alumina; silica gel; and magnesium perchlorate. The response time of the infra-red analyser was independent of the concentration of CO2 used (0-1%), but it was related to flow rate, dead space and the amount and drying agent used. At a low rate of 1 litre/min, alumina (145 g anhydrous weight) trapped virtually all the CO2 (0.8% in air) passing over it; silica gel (145 g anhydrous weight, mesh 6-20) adsorbed approximately 2 mmol CO2 (38% of total) over a period of 15 min; calcium sulphate (Drierite) absorbed a variable amount, depending on the bath; and calcium chloride adsorbed virtually no CO2. Increasing hydration of the drying agents reduced their capacity to adsorb CO2. Nitrogen was found to elute CO2 from the drying agents at about the same rate as it had been adsorbed. It is concluded that awareness of these adsorption/elution phenomena by drying agents should prevent errors from being made in the calibration of CO2 analysers, in the analysis of CO2, and in the measurement of specific activity or isotopic enrichment of CO2.

Adsorption↗
PubMed1985

Ultrastructural studies of vascular lesions in experimental amyloidosis of mice.

Definite lesions of arteriolar capillaries have been demonstrated in early amyloid lesions of mice. Pathologic changes include multiple endothelial gaps, the loss of an identifiable basal lamina, variable degrees of endothelial alteration, and the presence of the developing amyloid lesions surrounding the affected vessels. Despite these changes, the vessels remain functional part of the local microcirculation as demonstrated by intravascular injection of electron dense markers. These structural changes of arteriolar capillaries explain the presence of circulating plasma as a constant and major component of the early amyloid lesions in these animals and on this basis may determine the time of onset and site of formation of the lesions. The vascular injury appears to be caused by immunologic reactions to injected foreign antigens which gain a close relation to the structures of these vessels.

Amyloid↗
PubMed1983

Immunohistochemical indications of gastrin releasing peptide--bombesin-like immunoreactivity in the nervous system of the rat. Codistribution with substance P-like immunoreactive nerve terminal systems and coexistence with substance P-like immunoreactivity in dorsal root ganglion cell bodies.

Weak to strong gastrin releasing peptide--bombesin (GRP-Bn)-like immunoreactivity was found in fine varicose nerve terminal systems of low to high densities in several parts of the CNS. The highest densities of strongly immunoreactive terminals were found in the marginal layer and in the substantia gelatinosa of the spinal cord, and in parts of the nuc. tractus spinalis nervi trigemini. Morphometrical analysis in the spinal cord demonstrates that GRP-BN-like-immunoreactive and substance P (SP), but not somatostatin (SS)-immunoreactive nerve terminals strikingly codistribute. Coexistence of SP and GRP-BN-like immunoreactivities was demonstrated in trigeminal and spinal ganglion nerve cells. Thus, GRP-BN-like immunoreactivity may coexist with SP in certain SP-immunoreactive nerve terminal systems.

Animals↗
PubMed1983

Relationship between a pulmonary function test (FEV1) and the ADAPT quality-of-life scale.

In a previous study the Additive Daily Activities Profile Test (ADAPT) correlated .83 with maximum oxygen consumption among pulmonary rehabilitation patients. The present study expanded the pulmonary population base and compared the ADAPT scores of 41 patients at two independent centers with a more readily available parameter, the forced expiratory volume in the first second of forced exhalation (FEV1). The relationships between the two major ADAPT subscales and FEV1 were significant but lower in magnitude than that found with maximum oxygen consumption. The ADAPT continues to be sensitive to physical impairment and in translating the effect of impairment upon daily physical activity.

Activities of Daily Living↗
PubMed1983

The effect of a synthetic enkephalin analogue on postprandial gastrointestinal and pancreatic hormone secretion.

The effect of the synthetic enkephalin analogue Sandoz FK33-824 (DAMME) on gastric emptying and the postprandial secretion of upper gastrointestinal and pancreatic hormones was investigated in six healthy subjects. Gastric emptying was delayed as was the postprandial rise in glucose. There was significant blunting of insulin and gastric inhibitory polypeptide secretion, with complete abolition of the normal postprandial increases in pancreatic polypeptide and motilin. The secretion of gastrin was prolonged. These results demonstrate that pharmacological doses of opiate peptides inhibit gastric emptying and may have direct and indirect effects on gastrointestinal and pancreatic hormone secretion.

Adult↗
PubMed1981

Variant von Willebrand's disease and pregnancy.

The clinical course and coagulation profile of a pregnant patient with variant von Willebrand's disease were followed from the second trimester through puerperium. The clinical course was characterized by a normal delivery and absence of abnormal bleeding or need for replacement therapy. The coagulation profile demonstrated an increase in factor VIII procoagulant activity, factor-VIII-related antigen, and platelet aggregation activity in response to ristocetin prior to delivery. Postpartum, these factors decreased to prepregnancy values with distinctly different patterns. Factor VIII procoagulant activity continued to rise for 5 days after delivery and then decreased with a half-life of approximately 6 days. Factor-VIII-related antigen began to decrease just prior to delivery, displaying a half-life or approximately 6 days. Ristocetin cofactor activity, however, dropped immediately postpartum and displayed a half-life of approximately 6 hr. The ristocetin cofactor activity was associated with factor-VIII-related antigen, which displayed a significantly smaller molecular weight than does normal factor-VIII-related antigen. Larger aggregates of factor-VIII-related antigen. Larger aggregates of factor-VIII-related antigen did not appear during the pregnancy, and ristocetin cofactor activity could not be demonstrated in fragments of less than 0,8 x 10(6).

Adult↗