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Biomedical subjects

K Nelson

Publications and source records attributed to K Nelson.

At least 199 records · Page 11Linked to original sources
PubMed1987

Identification of a very large nuclear estrogen receptor complex.

A high mol wt estrogen receptor complex (mol wt: greater than 669,000) has been isolated from chromatin prepared from mouse uteri with the use of multiple protease inhibitors, exposure to DNAase I, and size exclusion HPLC (SEHPLC). This complex is stable in the presence of molybdate and 0.4 M KCl. Because receptors in the cytosol do not elute similarly to this large complex when investigated under a wide variety of conditions, it is unlikely that random receptor aggregation is responsible for the formation of this nuclear complex. Consequently, this complex may represent a collection of chromatin components that participate in the mechanisms of hormonal regulation. Since the large nuclear receptor complex can be isolated, this hypothesis can be readily subjected to extensive investigation.

Animals↗
PubMed1987

Soluble serum interleukin 2 receptor levels in leprosy patients.

Soluble interleukin 2 receptors (IL-2R) in sera of leprosy patients from Chiang Mai, Thailand, were quantified with a solid phase enzyme immunoassay using two monoclonal antibodies to the IL-2R. The IL-2R levels of untreated lepromatous, borderline lepromatous or midborderline patients and treated lepromatous and borderline lepromatous or treated borderline tuberculoid and tuberculoid patients were comparable to those of the Thai household or nonhousehold contacts; and they were significantly higher than the levels of USA control subjects. In contrast, IL-2R of untreated tuberculoid or borderline tuberculoid patients were significantly reduced. Patients with ongoing reversal reaction had very high circulating IL-2R, the levels of which correlated with fever and extent of skin lesions. Although erythema nodosum leprosum patients also had elevated IL-2R levels, they were significantly below those of patients with reversal reaction. When treated with corticosteroid, precipitous reduction of IL-2R was noted in all patients with reversal reaction but not in patients with erythema nodosum leprosum.

Enzyme-Linked Immunosorbent Assay↗
PubMed1986

Simultaneous measurement of epinephrine-induced platelet aggregation in 14 plasma samples.

A method is described for the simultaneous measurement of epinephrine-induced platelet aggregation in 14 different plasma samples in 15 min. It is based upon discontinuous registration of platelet aggregation and computer evaluation of the data. The samples are placed in holders mounted over magnetic stirring bars in a 37 degrees C water bath and the extinction is measured by removing the samples one after the other, placing them in a Braun Universal Aggregometer and returning them to their holders in the water bath. The time required to reach 37% of maximal aggregation was chosen as the evaluation criterion. It sufficed for the determination of aggregation sensitivity. This method for the first time permits measurement of a complete titration curve rapidly and under identical conditions and can be used to show the influence of a wide range of aggregation inducers and the concurrent effects of inducers plus various blocking agents. A correlation between aggregation sensitivity and alpha 2-receptor binding capacity in platelets, measured by competitive radioactive binding, was established in samples from 10 healthy volunteers. One group exhibited high aggregation sensitivity coupled with high alpha 2-binding capacity and the other showed low sensitivity with low binding capacity.

Aging↗
PubMed1986

Pharmacodynamics and pharmacokinetics of three different doses of urapidil infused in hypertensive patients.

The study was designed to follow the haemodynamic effects and pharmacokinetics under steady-state conditions of three different doses of urapidil infused continuously. Nine male hypertensive patients received three randomly assigned intravenous infusions of 32.5, 65 and 130 mg urapidil, over 14 h during 6 consecutive days, in a change-over fashion. Blood pressure and heart rate were measured over a period of 28 h after the infusion began and were compared with a reference profile obtained prior to the treatment periods. Urapidil and its main metabolite, parahydroxylated urapidil, were also determined for 28 h after the infusion began using HPLC. The 32.5 mg dose of urapidil caused a maximum decrease in systolic blood pressure of 33 +/- 8 mmHg, the 65 mg dose a maximum decrease of 39 +/- mmHg and the 130 mg dose a maximum decrease of 50 +/- 12 mmHg. The 32.5 and 65 mg doses resulted in similar serum urapidil concentrations, with maximum levels in the 100 to 200 ng/ml range, and the 130 mg dose caused a maximum level approximately four times that achieved with the 32.5 mg dose. The serum concentration of parahydroxy urapidil was proportional to the corresponding dose of urapidil. Four patients reported mild headache, fatigue, weakness, pressure in the head, perspiration and orthostatic dysregulation. The side-effects were probably drug related but required no specific therapy. In summary, the 32.5 mg dose of urapidil resulted in a pronounced decrease in blood pressure. The average pressure reduction over the 14-h infusion period showed further dose-dependent increases after the 65 and 130 mg doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1986

The effects of acute administration of cytotoxic anticancer agents on the capacity for subsequent hormonal responses in the mouse uterus.

The mouse uterus has been used as a model system with which to examine the interaction of anticancer agents with steroid hormone receptors and to evaluate the effect of a single exposure to a cytotoxic anticancer agent on the subsequent elicitation of the uterotrophic response to estradiol. The uterotrophic response was interpreted in terms of the induction of progesterone receptors, uterine weight gain and increased uterine DNA content. Evaluation of 34 cytotoxic agents selected for this study provided little evidence to substantiate the interaction of these agents with estrogen or progesterone receptors. Although prior treatment with certain cytotoxic agents partially inhibited the subsequent responses to estradiol, some capacity to respond to estradiol was always retained. The majority of cytotoxic agents had little impact on the capacity to respond to estradiol. Thus, in these studies where high sublethal concentrations of cytotoxic agents were administered prior to estradiol, there was no indication that the mechanisms regulating subsequent hormonal responses were compromised.

Animals↗
PubMed1986

Influence of different bisoprolol doses on hemodynamics, plasma catecholamines, platelet aggregation, and alpha 2- and beta-receptors in hypertensive patients.

This study was designed to evaluate the effects of the beta 1-selective adrenoceptor antagonist bisoprolol on blood pressure, heart rate, plasma catecholamines, platelet aggregation, and alpha 2- and beta-adrenoceptor density in 45 male hypertensive patients (WHO stages I-II). Following a two-week placebo phase, the patients received either 5, 10, or 20 mg bisoprolol in a double-blind randomized fashion, once daily for 12 weeks. On days - 14, 0, 1, 7, 28, 56, 84, and 1 and 2 weeks after discontinuation of treatment (administration of placebo), blood pressure and heart rate were measured in the supine and sitting position, as well as during and after a 15-min exercise period on a bicycle ergometer. Simultaneously with the hemodynamic measurements, blood samples were obtained for the determination of plasma catecholamines. Blood samples for the assessment of beta-receptor density on lymphocytes and alpha 2-receptor density on thrombocytes, as well as thrombocyte aggregation sensitivity, were collected before bicycle ergometry. Five, 10, and 20 mg bisoprolol caused dose-dependent reductions of blood pressure and heart rate at rest and at peak exercise. The responder rates (diastolic BP less than or equal to 90 mm Hg) were 33%, 67%, and 100% with 5, 10, and 20 mg bisoprolol, respectively. After discontinuation of active treatment, blood pressure and heart rate gradually returned to pretreatment values within 1-2 weeks. Plasma epinephrine and norepinephrine levels in patients in the supine position remained unchanged during the whole course of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1986

The reliability of axis V of DSM-III.

The authors studied the reliability of axis V of DSM-III by analyzing ratings of 97 psychiatric inpatients made by a multidisciplinary team of clinicians. The intraclass correlation coefficient for ratings of the overall sample was .49, lower than the figure found during the DSM-III field trials. The psychiatric diagnosis, age, ethnicity, marital status, and sex of the patient did not significantly influence reliability. The authors recommend more explicit instructions in the administration of the scale, the use of a standardized interview, and more training for raters as ways of increasing reliability.

Adaptation, Psychological↗
PubMed1986

Antagonism to estradiol in the mouse: reduced entry of receptors complexed with 4-hydroxytamoxifen into a Mg2+-soluble chromatin fraction.

Antagonism to estradiol has been examined in murine uteri. When tamoxifen was administered simultaneously with estradiol (0.05 microgram/mouse), it was able to act as an antagonist over the dosage range 0.05-50 micrograms/mouse. The metabolite 4-hydroxytamoxifen (4OH-tamoxifen) had high affinity for estrogen receptors and was a slightly better antagonist over the dosage range 0.005-1 microgram/mouse. After uteri were exposed to either [3H] estradiol or [3H]4OH-tamoxifen, receptors complexed with [3H] estradiol penetrated a chromatin region, which was released as the Mg2+-soluble chromatin fraction after DNAase I treatment more readily than receptors complexed with [3H]4OH-tamoxifen. [3H]4OH-tamoxifen-receptor complexes could not be driven into the Mg2+-soluble chromatin fraction by increasing the ligand concentration during translocation. Relative to [3H]estradiol, significantly more [3H]4OH-tamoxifen was observed to associate with uterine cells and to penetrate the nucleus so that neither restricted entry nor extranuclear partitioning could explain the failure of [3H]4OH-tamoxifen-receptor complexes to enter the Mg2+-soluble chromatin. Bleomycin, an agent that interrupts DNA continuity, did not interfere with the appearance of estrogen receptor activity in the Mg2+-soluble chromatin fraction. Preincubation of intact uteri in the presence of molybdate (20 mM) did inhibit the appearance of receptor activity in this chromatin fraction; however, this effect did not occur through inhibition of receptor activation, but, rather, through the lowering of receptor activity in all chromatin fractions. In the studies reported here, the chromatin positioning of estrogen receptors complexed with estradiol appeared to be distinct from the positioning of receptors complexed with 4OH-tamoxifen. These observations suggest an additional basis from which the mechanisms separating the actions of estrogen agonists and antagonists can be approached.

Animals↗
PubMed1985

Hydrodynamic characterizations of estrogen receptors complexed with [3H]-4-hydroxytamoxifen: evidence in support of contrasting receptor transitions mediated by different ligands.

Size-exclusion high-performance liquid chromatography was used to characterize the hydrodynamic molecular properties of estrogen receptors complexed with estradiol and the antiestrogen 4-hydroxytamoxifen. Cytoplasmic estrogen receptors complexed with [3H]-4-hydroxytamoxifen did not undergo reductions in hydrodynamic size after exposure to KCl or urea. Nuclear receptors complexed with 4-hydroxytamoxifen eluted as hydrodynamically larger molecules than nuclear receptors complexed with estradiol. Because identical hydrodynamic characterizations were obtained with the covalent ligand [3H]tamoxifen aziridine, these differences in chromatographic behavior are due to differences in ligand-mediated receptor properties and are not the result of ligand dissociation. When estrogen receptors, complexed with either [3H]estradiol or [3H]-4-hydroxytamoxifen, were exposed to trypsin, the receptors complexed with 4-hydroxytamoxifen eluted as larger hydrodynamic forms than receptors complexed with estradiol. These observations are interpreted to indicate that estradiol and 4-hydroxytamoxifen mediate contrasting transitions in the molecular orientation of estrogen receptors. The consequences of the transitions mediated by 4-hydroxytamoxifen appear to be that intermolecular associations become difficult to disrupt with KCl or urea and that the accessibility of trypsin-sensitive proteolytic sites becomes altered. Chromatin fractionation using DNase I and hypotonic Mg2+ solubilization identified a chromatin region that was less readily penetrated by receptors complexed with 4-hydroxytamoxifen than receptors complexed with estradiol.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Ossifying fibroma: a clinicopathologic study of sixty-four cases.

Sixty-four cases of neoplastic benign fibro-osseous lesions are presented, with clinical and radiographic follow-up in 23 instances. A marked predilection for female patients was observed, with the majority or cases arising in the molar-premolar region of the mandible. Radiographically, these neoplasms are well demarcated and may be radiolucent, radiolucent with central opacification (target appearance), or multilocular radiolucent. A benign fibro-osseous histopathologic pattern is observed with osseous, cemental, and/or ovoid-curvoid calcified deposits. This feature, along with confinement to tooth-bearing regions, supports a periodontal ligament origin. It appears that the distinction between cementifying and ossifying variants is academic, as no behavioral differences exist. The recurrence rate following curettage was found to be 28%.

Adolescent↗
PubMed1985

Leprosy associated with HLA-DR2 and DQw1 in the population of northern Thailand.

A study of the frequency of HLA-DR2 and DQw1 was performed in leprosy patients and controls in northern Thailand. HLA-DR2 was found in 100% (17/17) of patients with sporadic tuberculoid leprosy and in over 90% (30/32) of all tuberculoid leprosy patients, as compared to 62% (20/32) of controls (p = .02). These strong associations had relative risks of 21.4 for sporadic and 7.4 for all tuberculoid leprosy, and etiologic fractions of 1.0 and 0.84, respectively. There was also a statistically significant and strong association between tuberculoid leprosy and DQw1. These data add to the growing body of evidence that products of HLA class II determinants or closely linked genes may play a role in determining the clinical manifestations of M. leprae infection.

Adult↗