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Biomedical subjects

D L Hurley

Publications and source records attributed to D L Hurley.

At least 55 records · Page 3Linked to original sources
PubMed1989

Effects of oral contraceptive and estrogen administration on plasma calcitonin in pre- and postmenopausal women.

Estrogen (E) therapy and administration of oral contraceptives (OC) reportedly increase plasma calcitonin (CT) concentrations in women, effects said to mediate in part the beneficial actions of E on bone. To further examine this theory, we tested the effects of three cycles of OC therapy in 12 young women, comparing them to 10 healthy women before and after three normal menstrual cycles. We also determined the effects of 3 months of E therapy (ethinyl estradiol, 20 micrograms/day, 25 of 30 days) in 14 healthy postmenopausal women, using a crossover design (studied after 3 months with and 3 months without E). We determined CT by radioimmunoassay (antiserum G-1701) in whole plasma (iCT) and silica cartridge extracts of plasma (exCT) after overnight fasting, after calcium (Ca) infusion (2 mg Ca/kg over 5 minutes), and during a normal day at 0800, 1200, 1700, and 2000 h. In no control study was there a significant diurnal change in iCT or exCT, and neither OC nor E therapy altered this. Similarly, OC administration did not affect basal CT levels or the normal iCT and exCT responses to Ca infusion. E therapy induced expected changes in serum Ca, phosphorus, and alkaline phosphatase and urinary Ca and cAMP excretion; basal and diurnal plasma exCT levels were decreased significantly, consonant with the decrement in serum Ca. E did not alter normal iCT and exCT responses to Ca infusion. Thus, administration of either OC or E has no stimulatory effect on CT secretion, which suggests that the beneficial actions of E on bone are not mediated through CT-induced inhibition of bone resorption.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Nuclear DNA synthesis is blocked by UV irradiation in Dictyostelium discoideum.

We have used a thymidine auxotroph of the simple eukaryote, Dictyostelium discoideum and alkaline sucrose gradients of isolated nuclei to study alterations in DNA synthesis following irradiation of replicating haploid cells with 254 nm UV light. Three responses were characterized using pulse-chase protocols: (1) Lags in DNA synthesis as measured by the amount of label incorporated were 4, 9, and 20 h after 10, 50, and 200 J/m2. (2) The DNA synthesized during a 15-min pulse immediately after irradiation was of lower single strand molecular weight: 7, 3.5, and 3 x 10(6) dalton after 0, 50, and 200 J/m2. (3) The time required for maturation of the nascent DNA to full-sized single strands of about 2 x 10(8) dalton was 45-50 min for unirradiated cells, 3 h after 10 J/m2, and 20 h after 200 J/m2. The DNA of the irradiated cells did not mature uniformly during these delays; instead, a period of no increase in size was followed by a rapid, nearly control rate of maturation. We conclude: (a) at least some UV lesions block elongation of replicons; (b) the elongation of the replicons and their subsequent joining to yield mature high molecular weight DNA occurs after most of the lesions are repaired; (c) the timing of the different aspects of recovery suggest that initiation of replication is also inhibited.

Cell Nucleus↗
PubMed1989

Altered expression of spatially regulated embryonic genes in the progeny of separated sea urchin blastomeres.

We have examined the importance of the extracellular environment on the ability of separated cells of sea urchin embryos (Strongylocentrotus purpuratus) to carry out patterns of mRNA accumulation and decay characteristic of intact embryos. Embryos were dissociated into individual blastomeres at 16-cell stage and maintained in calcium-free sea water so that daughter cells continuously separated. Levels of eleven different mRNAs in these cells were compared to those in control embryos when the latter reached mesenchyme blastula stage, by which time cells in major regions of the intact embryo have assumed distinctive patterns of message accumulation. Abrogation of interactions among cells resulted in marked differences in accumulation and/or turnover of the individual mRNAs, which are expressed with diverse temporal and spatial patterns of prevalence in intact embryos. In general, separated cells are competent to execute initial events of mRNA accumulation and decay that occur uniformly in most or all blastomeres of the intact embryo and are likely to be regulated by maternal molecules. The ability of separated cells to accumulate mRNAs that appear slightly later in development depends upon the presumptive tissue in which a given mRNA is found in the normal embryo. Messages that normally accumulate in cells at the vegetal pole also accumulate in dissociated cells either at nearly normal levels or at increased levels. In one such case, that of actin CyIIa, which is normally restricted to mesenchyme cells, in situ hybridization demonstrates that the fraction of dissociated cells expressing this message is 4- to 5-fold higher than in the normal embryo. In contrast, separated cells accumulate significant levels of a message expressed uniformly in the early ectoderm but are unable to execute accumulation and decay of different messages that distinguish oral and aboral ectodermal regions. These data are consistent with the idea that interactions among cells in the intact embryo are important for both positive and negative control of expression of different genes that are early indicators of the specification of cell fate.

Animals↗
PubMed1988

Enhanced thymidine uptake causes the lowered thymidine requirement of D. discoideum auxotroph HPS 401.

Dictyostelium discoideum strain HPS 401 contains a spontaneous mutation that lowers the amount of thymidine required for cell growth relative to that of the auxotrophic parental strain HPS 400. Growth studies in defined medium show that as little as 8 micrograms thymidine/ml supports maximal growth of HPS 401, whereas 50 micrograms/ml is required by HPS 400. In contrast, both strains require over 40 micrograms thymidylate/ml to achieve maximal growth. HPS 401 exhibits thymidineless death when grown without thymidine; relative viability decreases to less than 0.01% after 190 h incubation. Assays for enzymes related to thymidine metabolism reveal that none of the strains tested (HPS 401, HPS 400, and prototrophic HPS 83 cells) contain detectable thymidine phosphorylase activity and that the specific activity of thymidine kinase is the same in these three strains. Thin-layer chromatography of extracts from cells grown on radiolabeled thymidine shows that there is no detectable conversion of thymidine to thymine in any of these strains. These analyses show that HPS 401 has rapid intracellular accumulation of thymidine, while only slight uptake is observed with HPS 400 or wild-type strains. HPS 401 also shows greater uptake of uridine in comparison to HPS 400 and wild-type cells. Thymidylate uptake was the same for all three strains. Thus, the mutation giving rise to the HPS 401 phenotype selectively increases the uptake of thymidine into the cell, where it can be efficiently utilized for DNA synthesis by the "salvage" pathways of nucleotide metabolism.

Cell Division↗
PubMed1988

Cosecretion of calcitonin gene products: studies with a C18 cartridge extraction method for human plasma PDN-21 (katacalcin).

PDN-21, the carboxyl-terminal flanking peptide encoded by the calcitonin (CT) gene, has been found in plasma of patients with medullary thyroid carcinoma and reportedly is cosecreted with CT. To test whether PDN-21 and CT are cosecreted in normal subjects, we developed a RIA for PDN-21 and measured immunoreactive CT and PDN-21 in whole plasma and silica or C18 cartridge extracts of plasma (exCT, exPDN-21) before and after calcium (Ca) infusion (2 mg Ca/kg over 5 min) in nine normal men and nine normal women. Plasma CT and immunoreactive PDN-21 levels were often below the assay detection limits. In contrast, basal exCT and exPDN-21 were detectable in all plasma samples, and the concentrations of both were significantly higher in men than in women [basal exCT (mean +/- SE): men, 4.8 +/- 0.3 ng/L; women, 2.4 +/- 0.3 (P less than 0.001); basal exPDN-21: men, 4.7 +/- 0.3 ng/L; women, 3.3 +/- 0.3 (P less than 0.01)]. Ca infusion sharply increased CT and PDN-21 concentrations in both sexes, but the increments were greatest in men [mean (+/-SE) increment of exCT: men, 37.2 +/- 3.9 ng/L; women, 15.7 +/- 4.3 (P less than 0.002); mean increment of exPDN-21: men, 29.7 +/- 4.7 ng/L; women, 11.0 +/- 3.1 (P less than 0.005)]. The molar concentrations of exCT and exPDN-21 were closely correlated (r = 0.97; P less than 0.001). With our antiserum, the extraction-concentration technique for measurement of PDN-21 had increased sensitivity and decreased nonspecific interference compared to the whole plasma assay. We conclude that CT and PDN-21 are cosecreted from normal thyroid C-cells under the control of extracellular fluid Ca, and that men have greater secretory capacity for both peptides than women. Plasma PDN-21 may serve alternatively to CT as a marker for C-cell activity.

Adult↗
PubMed1987

Axial and appendicular bone mineral density in patients with long-term deficiency or excess of calcitonin.

Whether calcitonin deficiency causes and calcitonin excess prevents bone loss is controversial. We therefore measured plasma calcitonin levels and bone mineral density at the radius (by single photon absorptiometry) and lumbar spine (dual photon absorptiometry) in patients with an excess or deficiency of calcitonin. We studied 21 patients who had undergone subtotal thyroidectomy 6.8 to 29 years previously and had no calcitonin secretory reserve, and 11 patients who had received a diagnosis of medullary thyroid carcinoma 6.8 to 23 years previously and had chronic hypercalcitoninemia. Bone-density values, expressed as Z-scores (i.e., as the number of standard deviations above or below the normal means adjusted for age and sex), were indistinguishable from normal in the patients who had undergone thyroidectomy (means +/- SE: radius, 0.36 +/- 0.15; spine, 0.27 +/- 0.17). In the patients with medullary thyroid cancer, radial bone-density values were normal (-0.26 +/- 0.39), but spinal density was significantly reduced (-0.75 +/- 0.17, P less than 0.01). There were no significant correlations between the duration of calcitonin excess or deficiency and the bone density at either site. Bone mineral density was not affected by whether or not thyroxine replacement therapy was given. We conclude that skeletal mass is not affected by endogenous plasma calcitonin in adults.

Adult↗
PubMed1984

Meningoencephalitis complicated by pituitary insufficiency and a spontaneously resolving suprasellar mass.

A 53-year-old woman presented with acute meningoencephalitis associated with anterior and posterior pituitary insufficiency. A computed axial tomogram (CT) of the head revealed a suprasellar mass. The meningoencephalitis, presumably of bacterial origin, resolved after antibiotic therapy and, on a repeat CT, the suprasellar mass had disappeared. Five months after the initial illness, the patient's diabetes insipidus had resolved, anterior pituitary function had improved, and there was no sign of the suprasellar mass. The presence of a suprasellar mass in conjunction with acute meningoencephalitis and anterior and posterior pituitary insufficiency should raise the suspicion that the mass is not neoplastic and may be infectious or inflammatory in origin.

Diabetes Insipidus↗
PubMed1983

Fever in adults. What to do when the cause is not obvious.

A fever can be trivial or serious, fleeting or protracted. When the cause is not obvious, a variety of diagnostic testing methods along with some ingenuity on the physician's part will usually be needed. Dr Hurley outlines the approach and discusses the special challenges presented when fever of obscure cause is protracted and when fever occurs in an immunocompromised patient.

Adult↗
PubMed1978

Role of complement in host defense against experimental disseminated candidiasis.

The role of complement in experimental disseminated candidiasis was studied in normal guinea pigs, animals congenitally deficient in the fourth component of complement (C4), and animals depleted of alternative pathway activity by cobra venom factor (CVF). Animals pretreated with CVF and challenged with Candida albicans had a high rate of mortality. Results of quantitative organ cultures corroborated prior reports that the kidney was the major target organ of infection. Infection of the kidney was markedly enhanced by CVF-induced depletion of the alternative pathway but not by classical pathway deficiency (deficiency in C4). There were differences among organs (kidney, liver, and spleen) in their requirement for complement to mount an effective host defense response. Ultimately, the integrity of the alternative pathway and late components of complement appears necessary for the limitation of and survival from sepsis due to C. albicans in nonimmune animals.

Animals↗
PubMed1977

Bone marrow necrosis associated with a Mucor infection.

Peripheral blood cytopenia due to documented marrow necrosis is an unusual occurrence. This report describes a diabetic patient who presented with profound anemia and thrombocytopenia. Extensive bone marrow necrosis was demonstrated. He had a large renal cyst that contained hyphae later identified as Mucor species. It is postulated that the marrow necrosis was a direct or indirect result of Mucor infection. The phenomenon of bone marrow necrosis in reviewed.

Aged↗
PubMed1977

Infectious complications of alcoholism.

Physicians must remain attuned to the increased incidence of infectious complications in alcoholics as compared with the general population. Prompt diagnosis and vigorous early treatment of pneumonia and spontaneous bacterial peritonitis may reverse and otherwise grave prognosis. Althought many mechanisms of host defenses seem affected by alcohol ingestion, the precise mechanisms of increased bacterial susceptibility in alcoholism remain unclear.

Alcoholism↗
PubMed1975

Disseminated candidiasis. i. an experimental model in the guinea pig.

A model of experimental disseminated candidiasis was developed in the guinea pig; Candida albicans was injected intraperitoneally or intravenously. The kidney was the most severely affected organ, with maximal colony counts of 26,208 plus or minus 9,152 colony-forming units/g of tissue five days after a sublethal inocluation (one-sixth of the 50% lethal dose) of viable organisms. The heart was the next most severely affected organ, and other organs were affected little. Histologic studies confirmed the data from colony counts and showed a progression of inflammation similar to that seen in human disease. A leukocytosis predominantly of mononuclear cells, and to a lesser degree of granulocytes, occurred and was maximal four days after inoculation. This model will provide the framework for a series of future studies of the various factors important in natural host defense against infection with Candida, as well as the effects of various immunosuppressive agents, particularly corticosteroids, on the development and expression of immunity and protection against infection.

Adrenal Glands↗
PubMed1975

Experimental disseminated candidiasis. II. Administration of glucocorticosteroids, susceptibility to infection, and immunity.

A model of experimental disseminated candidiasis in inbred guinea pigs was used for study of the effects of both short-acting and long-acting glucocorticosteroid administration on the susceptibility to infection, the development of in vivo and in vitro parameters of cell-mediated immunity, and the expression of already established Candida-specific, cell-mediated immunity. Results revealed that long-acting glucocorticosteroids markedly potentiated infection, increasing mortality and suppressing already established cellular immune parameters. The development of cellular immunity to Candida was not impaired. Short-acting glucocorticosteroids, however, did not potentiate infection, and they affected neither the development nor the expression of immune parameters.

Animals↗
PubMed1975

Cyclophosphamide suppression of established cell-mediated immunity. Quantitative vs. qualitative changes in lymphocyte populations.

The characteristics of cyclophosphamide-induced suppression of established ccll mediated immunity were studied in guinea pigs previously senstized to tuberculin. Cyclophosphamide treatment for 5 days produced a dose-dependent peripheral lymphoctopenia and disproportionatley greater neutrophenia which was particularly striking at high doses of 20 mg/kg per day(approximaetly 200 mg/kg-2 per day). Lymphoctes remianing in the circulation of cyclophosphamide treeated aniamls showed a doses-dependent reduction to both in vitro proliferactive and macrophage migration inhibitory factor responses to tuberculin compared to lymphocte responses of controls. Proliferative responses to phytohemaggultinin and concanavalin a were not significatly suppressed. Additional studies showed that cyclophosphamide suppressed the porliferactive and migration inhibitroy factor responses to tuberculin of lymph node and splenic as well as cirulating lymphocte populations. These studies showed that relatively short-term cyclophospamide administration produced immunosuppresion by quantitative as well as qualitative changes in lymphocyte populations. Significant suppresion of lymphocte function, howerver, was achived only with doses of cyclophoshamide which also produced a severe neutropenia.

Animals↗
PubMed1975

Immunosuppressive effects of glucocorticosteroids: differential effects of acute vs chronic administration on cell-mediated immunity.

The effects of acute vs. chronic glucocorticosteroid administration on established cellular immune responses were studied in guinea pigs previously sensitized to tuberculin. A greater than 50% reduction in circulating lymphocytes was observed 4 hr after injection of soluble hydrocortisone and 24 hr after daily subcutaneous injections of depot cortisone acetate. After a single dose of hydrocortisone, peripheral lymphocyte migration inhibitory factor (MIF) production and antigen and mitogen-induced proliferation were unchanged. However, the peripheral lymphocytes remaining in the circulation after chronic cortisone treatment showed a marked decrease in both antigen-induced MIF and proliferation, although mitogen responses remained normal. Although similar levels of lymphocytopenia were induced by acute and chronic glucocorticosteroid administration, only chronic treatment was associated with depression of certain cell-mediated lymphocyte functions. The available evidence suggests that these changes may depend on GCS-induced selective alterations in the circulation patterns of certain subpopulations of lymphocytes.

Animals↗