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Biomedical subjects

R L Reid

Publications and source records attributed to R L Reid.

At least 19 recordsLinked to original sources

Extracellular Tax1 protein stimulates tumor necrosis factor-beta and immunoglobulin kappa light chain expression in lymphoid cells.

The human T-cell leukemia virus type I tax1 gene product is responsible for the increased expression of several cytokine and cellular genes that contain NF-kappa B regulatory sequences. Our laboratory has previously demonstrated that purified, extracellular Tax1 protein induced the nuclear accumulation of NF-kappa B binding activity in lymphoid cells. Since HTLV-I infection causes increased levels of lymphotoxin tumor necrosis factor-beta [TNF-beta] and immunoglobulin secretion, we have studied the interaction of NF-kappa B proteins from Tax1-stimulated cells with the TNF-beta and immunoglobulin kappa (Ig kappa) light chain genes. Tax1 induction of NF-kappa B occurred in the presence of cycloheximide, and Tax1 stimulation did not result in increased levels of NF-kappa B or c-rel RNA. These results indicate that new synthesis of NF-kappa B proteins was not required for induction of NF-kappa B-binding activity. With use of the Ig kappa NF-kappa B-binding site as a probe, two distinct NF-kappa B gel shift complexes were induced by the Tax1 protein. A slower-migrating complex, C1, was inhibited by the addition of purified I kappa B. In contrast, the faster-migrating C2 complex was not inhibited by I kappa B, but C2 was increased by detergent treatment of cytoplasmic extracts, suggesting that its binding activity was also regulated by an inhibitor. The Tax1-stimulated proteins that interacted with the NF-kappa B-binding sites in the Ig kappa and TNF-beta promoters were distinct. A 75-kDa protein preferentially associated with the Ig kappa NF-kappa B-binding site. In contrast, a 59-kDa protein associated with the TNF-beta NF-kappa B-binding site. Tax1 stimulation led to increased levels of TNF-beta and Ig kappa mRNA, as measured by reverse transcription and polymerase chain reaction analysis. These results represent the first experimental evidence that extracellular Tax1 can regulate the expression of endogenous cellular genes.

Animals

Progesterone inhibits the estrogen-induced gonadotropin surge in the rhesus monkey independent of endogenous opiates.

Administration of an estrogen challenge during the luteal phase, a time when progesterone concentrations are elevated, fails to elicit a gonadotropin-positive feedback response. The purpose of the present study was to determine if endogenous opiates are involved in the mechanism by which progesterone blocks the estrogen-induced gonadotropin surge in monkeys. To this end, rhesus monkeys in the luteal phase were pretreated with either saline or various regimens of nalmefene, a long-acting opiate antagonist, before being given an estrogen challenge. Three groups of animals were given nalmefene (10 mg, iv) every 12 h beginning 24, 48, or 96 h before an estrogen challenge and continued until 48 h after the start of the estrogen challenge. A fourth group received a continuous sc infusion of nalmefene (20 mg/day) via osmotic minipumps beginning 48 h in advance of the estrogen challenge. In a second experiment, monkeys in the follicular phase received progesterone implants at the time of an estrogen challenge and iv injections of nalmefene every 12 h for 48 h. Gonadotropin and steroid levels were monitored in both experiments by collecting blood samples by saphenous venipuncture at intervals of 6-12 h. The majority of luteal phase animals that were pretreated with saline were unresponsive to the estrogen challenge. Only 2 of 16 (12.5%) had an increase in LH concentrations that could be classified as a surge. Animals pretreated with iv nalmefene every 12 h beginning 48 h before the estrogen challenge exhibited a higher incidence of positive feedback responses (8 of 12 or 66.7%). A concomitant FSH surge was observed in 3 of these instances. However, when progesterone concentrations, which declined before the estrogen challenge in the nalmefene-treated group, were supplemented with exogenous progesterone, nalmefene failed to evoke any LH surges. Six of 8 animals that received nalmefene by sc infusion exhibited LH responses. However, the amplitude and duration of these LH responses were diminished, and no FSH responses were observed. Monkeys pretreated with nalmefene for either shorter (24 h) or longer (96 h) periods before the challenge were less responsive (0 responses out of 6 trials and 1 response out of 4 trials, respectively). Nalmefene was equally ineffective in preventing progesterone inhibition of the estradiol-induced LH surge in follicular phase animals (0 of 15 animals had LH surge). These results indicate that nalmefene antagonism of endogenous opiates does not enable estrogen to exert positive feedback effects on LH release when progesterone levels are high, such as during the luteal phase or after progesterone administration.(ABSTRACT TRUNCATED AT 400 WORDS)

Analysis of Variance

Nutritive quality and palatability of switchgrass hays for sheep: effects of cultivar, nitrogen fertilization, and time of adaptation.

Feeding and palatability trials were conducted with four cultivars (cv) of switchgrass (Panicum virgatum L.), fertilized at three levels of N (0, 75, or 150 kg of N/ha) in 2 yr. Wether sheep had ad libitum access to chopped hays, and intake, apparent digestibility, particle passage rates, and concentrations of blood metabolites were determined. Palatability was measured with mature sheep in cafeteria trials. Nitrogen fertilization did not affect (P > .05) DM digestibility (DMD) or DMI, but there was a year x N interaction (P < .01) for NDF digestibility. Dry matter digestibility values for combined years and N levels were 56.9, 54.4, 56.6, and 57.9% (P < .01) for Pathfinder, New Jersey 50, Kentucky 1625, and Trailblazer cv, respectively; mean DMI values were 60.4, 60.8, 57.7, and 64.0 g/kg BW.75 (year x cv, P < .01). An apparently greater quality of Trailblazer was masked by weed invasion of N-fertilized stands of this cv in yr 2, with changes in hay composition. Lambs adapted to hay diets with time; mean DMI for cv and N levels combined increased (P < .001) from 50.5 to 71.4 g/kg BW.75 between wk 2 and 3 and wk 10 and 11, with no change in DMD. Intakes of NDF increased from 37.6 to 55.6 g/kg BW.75, an increase of 48%. Marker (Yb) measurements indicated little change in particle passage rates with treatment. There were no major differences in blood composition, apart from increases in blood urea N, as a result of N fertilization. Cafeteria trials showed preference by sheep for Trailblazer and KY 1625 compared with NJ 50 and Pathfinder, with a N x cv interaction (P < .01). Trailblazer was preferred to KY 1625 in a two-choice situation (P < .01). Results show relatively small effects of cv and N fertilization on quality of switchgrass and indicate the need for a lengthy period of adaptation by sheep to the feeding of a warm-season grass.

Animal Feed

Energy and protected protein supplements to lambs on endophyte-infected tall fescue pasture.

The effect of supplements on intake, digestibility, N retention, ADG and blood and body composition of growing lambs fed cut herbage or grazing KY 31 tall fescue (Festuca arundinacea Schreb.) pastures at two levels of N fertilization (92 and 318 kg/ha) was determined. Supplements were corn (C), corn with soybean meal (U-SBM) and corn with heat-treated SBM (H-SBM). Metabolism trials were run at three growth stages in the 1st yr with 24 lambs. Although all supplements increased total DMI and DM digestibility, they decreased NDF digestibility relative to grass (G), with no difference between supplements; C depressed apparent CP digestibility. Nitrogen retention increased from -2.5 g/d on G to -.4 g/d on C and 3.2 and 4.1 g/d on U-SBM and H-SBM, respectively, for combined periods and N rates. Blood urea N (BUN) concentrations differed (P less than .01) in the following order: G greater than U-SBM greater than H-SBM greater than C. In the 2nd yr, lambs (n = 64) grazed fescue pastures at the same N fertilizer rates and were given the same supplements. Gains were not different (P less than .05) on low-N (LN) and high-N (HN) pastures. Seasonal ADG were 80, 115, 122 and 130 g/d for G, C, U-SBM and H-SBM treatments, respectively, with no difference (P less than .05) between U-SBM and H-SBM. At slaughter, lambs from G had lower dressing percentages (P less than .05) and fat content (P less than .01) than lambs on C, U-SBM and H-SBM treatments, with no differences between supplements. Results indicated a better performance of growing lambs on fescue with both energy and protein supplements. Response to protected vs unprotected protein was small.

Acremonium

Effects of nitrogen and sulfur on digestion and nutritive quality of warm-season grass hays for cattle and sheep.

The influence of N and S on the usage of warm-season grasses was examined in two metabolism trials with cattle and sheep. Effects of N fertilization (75 kg N from urea/ha) on digestibility, intake, and ruminal mineral solubilization of switchgrass (Panicum virgatum L.; SWG) and big bluestem (Andropogon gerardii Vitm.; BB) hays were determined in a 4 x 4 Latin square experiment with mature steers. Effects of N and S applied as urea and sodium sulfate in spray form to SWG hay were estimated in a 2 x 3 factorial experiment using sheep. Dry matter and NDF digestibility was greater (P less than .03) for BB than for SWG, and intake of SWG was 10% greater (P less than .06) than that of BB. Fertilizer N increased DMI (P less than .02) of SWG and BB by cattle by 11.4 and 16.1%, respectively. Fertilization decreased (P less than .04) ruminal turnover times by 9.3 and 18.5% for SWG and BB, respectively. In situ DM degradation rates were faster (P less than .02) for fertilized than for unfertilized forages and were faster (P less than .06) for BB than for SWG. In the sheep trials, levels of CP in SWG diets were 7.2 and 9.5%: levels of S were .12, .20, and .29%, respectively. Urea supplementation increased (P less than .01) hay intake by 9.4% and also increased (P less than .01) digestibility of DM and NDF. Supplemental S had no effect (P greater than .05) on any measurement. There was no effect (P greater than .05) of supplemental N on ruminal retention times, rates of passage, or apparent retention of N and S. The provision of extra N by fertilization or dietary supplementation improved the nutritional quality of the low-protein, warm-season grass hays studied in this experiment, whereas no response to dietary S was detected.

Animal Feed

Soluble HTLV-I Tax1 protein stimulates proliferation of human peripheral blood lymphocytes.

Human T-cell leukemia virus type I (HTLV-I) is associated with two human diseases, adult T-cell leukemia (ATL) and tropical spastic paraparesis/HTLV-I associated myelopathy (TSP/HAM). Lymphocytes from patients with ATL or TSP/HAM display abnormal proliferation properties in culture. Here we report that purified, soluble Tax1 protein can be taken up by, and stimulate proliferation of, uninfected human peripheral blood lymphocytes (PBLs) that have been stimulated with phytohemagglutinin (PHA). Tax1 was 40 to 70% as active as interleukin-2 (IL-2) in stimulating proliferation of PBLs. Heat inactivation, chloroform extraction, and immunoprecipitation with antisera specific for Tax1 each abolished the ability of the protein to stimulate lymphocyte proliferation. Tax1 failed to stimulate PBL proliferation in the absence of PHA. After an initial round of cell division, Tax1-treated PBLs exhibited prolonged sensitivity to IL-2-induced proliferation. These results indicate that Tax1 can stimulate lymphocyte proliferation in culture and imply that extracellular Tax1 may be involved in the spontaneous proliferation of TSP/HAM lymphocytes and the IL-2-dependent proliferation of ATL lymphocytes.

Blotting, Western

A randomized, double-blind, placebo-controlled, cross-over trial to assess the side effects of medroxyprogesterone acetate in hormone replacement therapy.

Cyclic progestin therapy has been widely advocated as an adjunct to postmenopausal estrogen replacement therapy to reduce the risk of endometrial carcinoma. Acceptance of this approach, however, appears to have preceded detailed evaluation of possible adverse side effects of progestins that could result in patient noncompliance. We evaluated the nonmenstrual physical and psychological side effects of oral medroxyprogesterone acetate given in conjunction with transdermal estrogen in two groups of women with previous hysterectomy and oophorectomy. Twenty-four women with prospectively documented severe premenstrual syndrome (PMS) before surgery and 24 women with no such history of adverse premenstrual changes received transdermal estrogen 100 micrograms on days 1-25 and either oral medroxyprogesterone acetate 10 mg daily or an identical placebo (days 12-25) in a randomized, double-blind, cross-over design. Mood and physical symptoms were monitored prospectively, using daily self-ratings on the Daily Symptoms Checklist. The Beck Depression Inventory and Premenstrual Tension Self-Rating Scale were completed on day 24. At the study's completion, the patients were asked which treatment period they preferred. Paired comparisons did not reveal any significant differences, and preference for treatment was equally divided between medroxyprogesterone acetate and placebo. We conclude that addition of medroxyprogesterone acetate 10 mg/day for 14 days to cyclic transdermal estrogen therapy (days 1-25) produces no consistent adverse physical or psychological effects on women for one cycle of treatment, regardless of their PMS history.

Double-Blind Method

Lasting response to ovariectomy in severe intractable premenstrual syndrome.

A total of 14 women with severe premenstrual syndrome unresponsive to conservative medical therapy were treated with danazol in doses sufficient to suppress cyclic ovarian steroidogenesis. In each case medical ovarian suppression resulted in complete relief from symptoms. For ongoing symptom relief, each woman elected to undergo bilateral ovariectomy and concomitant hysterectomy. Both medical ovarian suppression and ovariectomy with low-dose conjugated estrogen therapy afforded lasting relief from cyclic symptoms of premenstrual syndrome and a corresponding improvement in overall quality of life. We conclude that cyclic ovarian steroidogenesis is a powerful determinant for the expression of premenstrual symptomatology. Ovariectomy with low-dose estrogen replacement is an effective alternative for the woman with debilitating premenstrual syndrome who does not respond to conventional interventions.

Adult

Effect of menstrual cycle phase and oral contraceptive use on serum lithium levels after a loading dose of lithium in normal women.

Serum lithium levels were analyzed in six healthy, normal women during the midfollicular, midluteal, and premenstrual phases of their menstrual cycles after they had received 300 mg of lithium carbonate orally. An identical protocol was followed for seven women with artificial cycles induced by oral contraceptive steroids. Analysis of variance for repeated measures over time showed no significant differences between groups or between cycle phases. Therefore, hormonal effects of ovarian or contraceptive steroids per se do not appear to alter serum lithium concentrations. Other factors may account for changing lithium requirements during the menstrual cycle in some patients with affective illness.

Contraceptives, Oral

Comparative utilization of warm- and cool-season forages by cattle, sheep and goats.

The quality of different classes of forage hay (C3, C4 grasses and legumes) was determined in intake and digestibility trials with mature cattle, sheep and goats. For all nine hays, DM and NDF digestibility by cattle and goats was higher (P less than .05) than by sheep, with no differences due to forage class. Cattle had a higher (P less than .01) DM intake than sheep or goats averaged across forage (92.6 vs 65.8 and 68.6 g/kg BW.75); hay intake was highest on legume, with no difference between C3 and C4 grasses. Mean NDF intake by cattle was greater than by sheep or goats (58.7 vs 39.6 and 42.6 g/kg BW.75); NDF intake for all animal species decreased in the order C4 grass greater than C3 grass greater than legume. Particle passage rates did not differ (P greater than .05) with forage class but were higher (P less than .02) for sheep and goats than for cattle. Prefeeding ruminal DM fill values, determined by emptying, were 10.6, 15.0 and 19.9 g/kg BW1.0 for alfalfa, orchardgrass and switchgrass hays fed to cattle, and 11.2, 11.3 and 16.5 g/kg BW1.0 for the same hays fed to sheep. Estimated turnover times for DM and NDF were shorter (P less than .05) for sheep than for cattle; DM turnover was longer for switchgrass than for alfalfa and orchardgrass, with no forage differences in NDF turnover between these two animal species. Results show that goats were superior to sheep in NDF digestion.

Animal Feed

Unexplained infertility: evaluation of treatment with clomiphene citrate and human chorionic gonadotropin.

A double-blind, randomized, prospective therapeutic trial was conducted in 148 couples with unexplained infertility. Treatment consisted of 4 consecutive months of placebo or clomiphene citrate (CC) (100 mg) by mouth on cycle days 5 to 9, and placebo or human chorionic gonadotropin (hCG) (5,000 IU) intramuscularly on cycle days 19, 22, 25, and 28. There were 14 pregnancies during the trial and 39 pregnancies during observation before and after the trial. Placebo treatment resulted in no pregnancies over 4 months. Clomiphene citrate was significantly better than placebo (P less than 0.04), with a pregnancy rate of 19% over the course of 4 months. The pregnancy rate with hCG either alone (11%) or in combination with CC (7.6%), was not significantly better than placebo. Treatment-independent pregnancies, defined as those before treatment (but after enrollment), or more than 1 month after therapy, occurred in 16% of the couples, with a mean time to conception of 8.8 months. As part of their follow-up, 39 of the study couples subsequently underwent in vitro fertilization (IVF), and 43% were found to have a previously unrecognized male factor or fertilization defect. A pregnancy rate of 16% was achieved after a mean of 1.1 cycles in these 39 couples. The authors conclude that CC is useful in treating unexplained infertility and is a reasonable initial therapy. For couples who fail to conceive, IVF may be diagnostic as well as therapeutic.

Adult

Comparison of the duration of action of nalmefene and naloxone on the hypothalamic-pituitary axis of the rhesus monkey.

The duration of action of nalmefene, a relatively new opiate antagonist, on the hypothalamic-pituitary axis of the rhesus monkey was compared to that exhibited by naloxone. Ovariectomized monkeys (n = 5) were pretreated with 10 mg nalmefene, 10 mg naloxone or an equivalent volume of saline 12, 24, or 48 h prior to the administration of 10 mg morphine. Blood samples were collected by venipuncture 0, 1, 2, 3 and 4 h after injection of morphine and were assayed for luteinizing hormone (LH) and prolactin (PRL). Duration of action of these two opiate antagonists was estimated from their ability to block morphine inhibition and stimulation of LH and PRL release respectively. Morphine reduced serum LH concentration by 60% and increased PRL levels approximately 4-fold in saline-pretreated animals. Administration of nalmefene either 12 or 24 h, but not 48 h prior to morphine, significantly antagonized the effects of this opiate on LH and PRL release. In contrast, naloxone at all pretreatment intervals failed to block morphine's effect. We conclude that a single 10 mg bolus injection of nalmefene exerts significant activity at the opiate receptors that mediate the effects of morphine on LH and PRL release for at least 24 h after administration, whereas the same dose of naloxone has a duration of action less than 12 h. Based on this finding it is likely that the effects of endogenous opioid peptides in the rhesus monkey can be chronically antagonized by the daily administration of nalmefene.

Animals

The paradoxical stimulatory effect of morphine on LH secretion is dose-dependent and naloxone-reversible.

We previously observed that morphine stimulated luteinizing hormone (LH) secretion from ovariectomized rats when administered intravenously at a dose of 10 mg/kg body weight. The objectives of the present study were to determine: (1) if this paradoxical effect of morphine on LH secretion could be antagonized by naloxone; (2) whether beta-endorphin also stimulated LH secretion under similar conditions; (3) what influence, if any, the ovaries have on the expression of this opiate-induced LH secretion, and (4) whether this paradoxical effect of morphine extended to prolactin (PRL) secretion. An intravenous injection of morphine, 10 mg/kg body weight, to ovariectomized rats acutely increased both plasma LH and PRL concentrations. The LH and PRL responses were completely antagonized by the concurrent administration of the opiate antagonist naloxone (1 mg/kg body weight). In contrast, morphine suppressed LH concentrations and had no effect on PRL levels when injected at a dose of 1.0 mg/kg body weight. Intravenous injections of beta-endorphin, 1 mg/kg body weight, increased PRL concentrations to a level comparable to that observed following morphine, 10 mg/kg body weight, and produced a transient but insignificant inhibition of LH release. Intraventricular injections of much lower doses of beta-endorphin resulted in a dose-dependent suppression of LH release and a dose-dependent stimulation of PRL release in ovariectomized rats. Intravenous administrations of morphine (10 mg/kg), but not beta-endorphin (1 mg/kg), to normal female rats resulted in a 2-fold increase in LH concentrations similar to that observed in ovariectomized rats, whereas both treatments similarly increased PRL concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Influence of the menstrual cycle on airway function in asthmatic and normal subjects.

Investigations of premenstrual asthma (PMA) have been based on studies of asthmatics already aware of a deterioration of asthma premenstrually. Little is known, therefore, about relationships between the menstrual cycle and airway function in asthmatics who do not complain of PMA or in normal subjects. We investigated airway function in both of these groups for three or four consecutive menstrual cycles. Daily records of asthma symptoms and peak expiratory flow rates were maintained by 11 asthmatics and 29 normal control subjects. Standard spirometry and serum estradiol and progesterone levels were measured during the follicular, midluteal, and late luteal phases of the menstrual cycle. Airway reactivity to methacholine was tested during the follicular and luteal phases. The normal group showed no significant changes in symptoms, peak flow rates, spirometric parameters, or airway reactivity. Although the asthmatic group also demonstrated no significant changes in spirometry and airway reactivity, asthma symptoms (shortness-of-breath, cough, wheeze, and chest tightness) deteriorated significantly (p less than 0.001) from the follicular to the luteal phase, as did the morning peak flows of the asthmatics (p = 0.045). Airway function and reactivity were not related to hormone levels in either group. This study indicates that asthmatics not previously aware of PMA will record a premenstrual worsening of asthma symptoms and peak expiratory flow rates. These changes are not related to a deterioration in spirometry and airway reactivity or to the absolute levels of circulating progesterone and estradiol.

Adult

Naloxone antagonism of corticotropin-releasing hormone stimulation of prolactin secretion in rhesus monkeys.

The effect of opiate receptor blockade on human CRH-induced PRL secretion was examined in ovariectomized and normal female rhesus monkeys. A bolus iv dose of 100 micrograms CRH acutely stimulated PRL secretion in both normal and ovariectomized animals. The magnitude of the PRL response was greater in ovariectomized monkeys (212% increase; n = 5) than in normal monkeys (56% increase; n = 5). Naloxone pretreatment inhibited CRH-induced PRL release in a dose-dependent fashion, whereas nalmefene did not, in both normal and ovariectomized monkeys. Administration of nalmefene alone significantly stimulated PRL secretion in normal monkeys (57% increase; n = 10), but not in ovariectomized monkeys (10% increase; n = 10). Naloxone alone had no effect. Since nalmefene has a high affinity for both the kappa- and mu-receptors whereas naloxone binds primarily to the mu-receptor, these results suggest that CRH-induced PRL secretion in monkeys is mediated by an endogenous opiate which binds to an opiate receptor other than or in addition to the mu- and kappa-receptors.

Animals

Role of the community orthopaedic surgeon in rehabilitation of the stroke patient.

The purpose of the paper is to describe the role and function of the community orthopaedic surgeon in assisting with the rehabilitation of the stroke patient. Emphasis is on total patient rehabilitation with guidelines to nursing education, splinting, bracing, and selection of appropriate orthopaedic surgical procedures. The different treatment goals of the upper and lower extremity stroke patient is stressed.

Cerebrovascular Disorders