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W C Duncan

Publications and source records attributed to W C Duncan.

At least 37 records · Page 2Linked to original sources
PubMed1996

Measurement of circulating inhibin forms during the establishment of pregnancy.

This study investigated the forms of inhibin released into the circulation 1) in very early pregnancy, 2) after stimulation of the corpus luteum by exogenous hCG, and 3) in abnormal and failing human pregnancy. Samples were assayed by enzyme-linked immunosorbent assays for inhibin A, inhibin B, and inhibin pro-alphaC-related immunoreactivity (pro-alphaC-RI). The concentration of inhibin A rose steadily during the conception luteal phase to an initial peak 12 days after ovulation (104 +/- 23 pg/mL), then rose rapidly to a further peak 43 days after ovulation 424 +/- 6 pg/mL). The concentration of pro-alphaC-RI exhibited a much larger peak on day 15 after ovulation (1423 +/- 361 pg/mL), but fell thereafter. The concentration of inhibin B was low after ovulation and subsequently barely detectable in pregnancy. hCG treatment resulted in a significant rise in the concentrations of inhibin A and pro-alphaC-RI, but had no effect on the inhibin B concentration. The pro-alphaC-RI concentration was a better indicator of continuing pregnancy viability than either hCG or inhibin A. Early trophoblast secretes proportionately more bioactive inhibin than the corpus luteum. The corpus luteum and trophoblast do not secrete inhibin B into the circulation. These data support the concept of different physiological roles for different inhibin forms.

Abortion, Spontaneous↗
PubMed1996

Expression of tissue inhibitor of metalloproteinases-1 in the human corpus luteum after luteal rescue.

Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a specific inhibitor of a group of proteolytic enzymes known as matrix metalloproteinases. These enzymes have been widely implicated in the process of tissue remodelling. Extensive remodelling occurs in the corpus luteum during luteolysis unless human chorionic gonadotrophin (hCG) is produced by the early conceptus. This study aimed to investigate the expression and localisation of TIMP-1 in human corpora lutea during the luteal phase of the cycle and after luteal rescue with exogenous hCG to mimic the changes of early pregnancy. Human corpora lutea from the early (n = 4), mid- (n = 4) and late (n = 4) luteal phases and after luteal rescue by hCG (n = 4) were obtained at the time of hysterectomy. Expression of TIMP-1 was investigated in these tissues by Western blotting, immunohistochemistry, Northern blotting and in situ hybridisation. Luteal cells of thecal origin were distinguished from those of granulosa origin by immunostaining for 17 alpha-hydroxylase. A 30 kDa protein consistent with TIMP-1 was detected in human corpora lutea. This protein was localised to the granulosa lutein cells in all tissues examined. TIMP-1 mRNA was found in large quantities in all glands examined and this again localised to the granulosa lutein cells. The expression and localisation of TIMP-1 did not change throughout the luteal phase and was not altered by luteal rescue. The function of this uniform expression of TIMP-1 in the corpus luteum is not clear but these data suggest that the inhibition of structural luteolysis during maternal recognition of pregnancy is not mediated by regulation of TIMP-1 expression.

Adult↗
PubMed1996

Expression of tissue inhibitor of metalloproteinases-1 in the primate ovary during induced luteal regression.

Although tissue inhibitor of metalloproteinases-1 (TIMP-1) is one of the major secretory products of the corpus luteum, the functional significance of this is not clear. In addition to its role as a specific inhibitor of the matrix metalloproteinase enzymes involved in tissue remodelling, it has recently been suggested that TIMP-1 is also a potent stimulator of steroidogenesis in vitro. However, in the ruminant, TIMP-1 expression increases during luteal regression. This study sought to determine (i) the effect of induced luteal regression on ovarian TIMP-1 expression in the primate and (ii) the expression of TIMP-1 in other steroidogenic and non-steroidogenic tissues. Marmoset ovaries were studied on day 10 of the normal luteal phase and 12 and 24 h after induced luteolysis, with either gonadotrophin-releasing hormone (GnRH) antagonist or prostaglandin F2 alpha analogue. Ovaries from different stages of the normal ovarian cycle were also studied. Expression of TIMP-1 was investigated by isotopic in situ hybridisation. TIMP-1 expression was also examined in a wide range of other marmoset tissues by Northern blotting and in situ hybridisation. TIMP-1 was found to be highly expressed in the marmoset corpus luteum. Luteolysis induced with either prostaglandin F2 alpha or GnRH antagonist was associated with a significant fall in TIMP-1 expression in luteal tissue. TIMP-1 mRNA was also localised to ovarian follicles throughout the ovarian cycle. Expression occurred in the thecal layer of smaller follicles (< 1.5 mm) and the granulosal layer of larger pre-ovulatory follicles. In atretic follicles, TIMP-1 was highly expressed at the interface between the thecal and granulosal cells. TIMP-1 was found to be predominantly expressed in steroidogenic tissues, particularly the ovary, adrenal and placenta. These data support a role for changes in TIMP-1 expression in tissue remodelling in the ovary and are consistent with an additional function of TIMP-1 as a facilitator of steroidogenesis.

Animals↗
PubMed1996

Hypothenar hammer syndrome: an uncommon cause of digital ischemia.

Unilateral digital ischemia may occur as a result of repetitive use of the hypothenar eminence as a hammer, with resultant damage to the wall of the ulnar artery and the superficial palmar arch. Secondary thrombus formation from intimal damage and potential embolization may cause signs and symptoms of arterial insufficiency in the second through fifth digits. Three automobile mechanics with unilateral ischemia caused by hypothenar hammer syndrome are described. All three patients had improvement with conservative treatment and continued to work with only minimal disability.

Adult↗
PubMed1995

Antidepressant drug-induced hypothalamic cooling in Syrian hamsters.

Antidepressant drugs have been reported to alter the circadian pattern of body temperature, but specific effects on the amplitude or on average body temperature are not consistent, and there have been no specific studies to examine chronic drug effects on brain temperature. To address these issues, hypothalamic temperature (Thy) was monitored telemetrically in hamsters treated with three antidepressant drugs: the monoamine oxidase inhibitor (MAOI), clorgyline; the 5HT reuptake inhibitor, fluoxetine; and the alkali metal, lithium. For comparison, hamsters were also treated with two neuroleptic drugs, chlorpromazine and haloperidol. Each of the three antidepressant drugs, but neither of the neuroleptic drugs, produced a chronic decrease in diurnal (rest-phase) hypothalamic temperature. The Thy-decreasing effect of clorgyline was not prevented by pinealectomy, and Thy decreased more than peritoneal temperature (Tp), thus reducing the temperature difference between the hypothalamus and the peritoneal cavity. Less general effects of the antidepressants were also observed. Clorgyline and fluoxetine, but not lithium, delayed the 24-hour rhythm of Thy. Clorgyline and lithium, but not fluoxetine decreased the average 24-hour Thy. The neuroleptics chlorpromazine and haloperidol decreased the amplitude of the 24-hour Thy rhythm. The fact that chronic antidepressant drugs, but not neuroleptic drugs, decrease Thy is consistent with their different neurotransmitter effects and clinical applications, and raises the possibility that their antidepressant property might be related to their capacity to decrease Thy during sleep.

Animals↗
PubMed1995

Immunolocalization of bcl-2 protein in human endometrium in the menstrual cycle and simulated early pregnancy.

Cell death by apoptosis is now regarded as an important feature of normal endometrial physiology. Recent reports have suggested that bcl-2, a proto-oncogene responsible for the suppression of apoptosis, is expressed in endometrium and may be involved in the regulation of menstruation. Using standard immunohistochemical procedures, the immunoreactivity of bcl-2 and progesterone receptors has been investigated in normal human endometrium throughout the menstrual cycle (n = 25) as well as endometrium exposed to continued oestradiol and progesterone stimulation by 'rescue' of corpus luteum (n = 4) with exogenous human chorionic gonadotrophin (HCG) administration (pseudopregnancy). Marked immunoreactivity, consistent with previous reports, was noted in the glandular epithelium during the proliferative phase of the cycle. Immunostaining persisted in the glandular epithelium during the secretory phase, although the percentage and intensity of staining was markedly reduced. Staining in the stromal compartment was only noted during the late secretory phase of the cycle. Co-localization with an antibody against CD56 demonstrated that this immunoactivity largely reflected the presence of lymphocytes in the stroma. Endometrium from subjects who underwent 'luteal rescue' displayed limited immunostaining in either glands or stroma. The absence of significant bcl-2 expression in endocrinologically maintained endometrium makes it highly unlikely that bcl-2 is important in prolonging endometrial cell survival in the luteal phase of the menstrual cycle.

Adult↗
PubMed1995

Immunolocalization of bcl-2 in the human corpus luteum.

The mechanisms of luteal regression and rescue in women are unknown but forms of programmed cell death may be involved. The proto-oncogene bcl-2 is an important inhibitor of apoptosis but has not previously been described in the human corpus luteum. Immunohistochemical localization of bcl-2 protein was investigated in human corpora lutea obtained from women undergoing surgery during endocrine monitored menstrual cycles as well as from women who had been treated with human chorionic gonadotrophin (HCG) to prolong the luteal phase. Bcl-2 was found to be localized in granulosa-lutein, theca-lutein (as identified by co-localization of P450(17)alpha-hydroxylase) and the endothelial cells around some blood vessels. Immunoblotting demonstrated the presence of a single band of approximately MW 26 kDa. There was no apparent change in either the intensity of immunostaining or the histological localization during the normal luteal phase or following treatment with human chorionic gonadotrophin. The product of the proto-oncogene bcl-2 is present in the human corpus luteum. It is unlikely that bcl-2 expression alone is responsible for prolongation of the lifespan of the corpus luteum in early pregnancy although it is possible that the action of the bcl-2 gene present is modified by changes in other members of the bcl-2 family.

Adult↗
PubMed1995

Measurement of creatine kinase activity and diagnosis of ectopic pregnancy.

OBJECTIVE: To investigate whether the measurement of maternal plasma creatine kinase concentration is of clinical value in the diagnosis of tubal ectopic pregnancy. DESIGN: A retrospective observational study covering a three month period. SETTING: The gynaecological emergency service of a UK teaching hospital. SUBJECTS: One hundred and twenty women presenting with clinical suspicion of an ectopic pregnancy such that plasma human chorionic gonadotrophin (hCG) concentration was measured. MAIN OUTCOME MEASURES: Plasma hCG and creatine kinase concentrations were measured. Pregnancies were classified as ectopic pregnancy, complete miscarriage, incomplete miscarriage or ongoing pregnancy. Pregnancies were further classified as uncertain diagnosis if the diagnosis was not clear after initial investigation. RESULTS: Twenty-one of the patients had an ectopic pregnancy. Diagnosis was classified as uncertain in 48% of pregnancies studied and in 54% of ectopic pregnancies during the study period. The mean plasma creatine kinase was higher in ectopic pregnancies than other pregnancies in the study group (P < 0.01) and remained higher in the subgroup of patients with uncertain diagnosis (P < 0.05) but there were significant overlaps in creatine kinase concentrations in all four clinical groups. When a cut-off point of 45 iu/l is used, the measurement of plasma creatine kinase activity has a sensitivity of 0.57 and a specificity of 0.67 for the diagnosis of ectopic pregnancy.

Chorionic Gonadotropin↗
PubMed1994

The interaction of thyroid state, MAOI drug treatment, and light on the level and circadian pattern of wheel-running in rats.

In order to examine the relationship between thyroid status, the circadian system, and antidepressant drug response, the antidepressant drug clorgyline, a monoamine oxidase inhibitor (MAOI), was administered chronically to sham-operated or thyroparathyroidectomized rats. Wheel-running was monitored continuously in a light-dark (LD) cycle, and then in constant dim light. In LD, MAOI treatment increased levels of running. This effect was delayed in hypothyroid rats relative to euthyroid rats. In constant light, the MAOI-induced increase in running was diminished in euthyroid but not hypothyroid animals. Hypothyroid animals were less responsive to the change in lighting than were euthyroid animals, and this was more apparent in hypothyroid rats given MAOI. The daily pattern of running differed with lighting condition as well as with treatment group. MAOI-treatment of hypothyroid animals phase-advanced the pattern of wheel-running. MAOI-treatment of control animals increased the amplitude of wheel-running particularly in the LD cycle. These results indicate that thyroid status, lighting, and MAOI treatment interact to alter the behavioral response to chronic drug treatment.

Animals↗
PubMed1994

Autonomic and behavioral thermoregulation in the golden hamster during subchronic administration of clorgyline.

Chronic administration of clorgyline, a type-A monoamine oxidase inhibitor, leads to a decrease in peritoneal (i.e., core) temperature of golden hamsters. To better understand the mechanisms of clorgyline's thermoregulatory effects, autonomic and behavioral thermoregulatory effectors were measured in Syrian hamsters following chronic infusion of clorgyline via a minipump (2 mg/kg/day). Metabolic rate, evaporative water loss, motor activity, and core temperature were measured after 60 min of exposure to ambient temperatures (Ta) of 5, 20, 30, and 35 degrees C. Behavioral thermoregulatory responses were assessed by measuring selected Ta and motor activity of the same animals in a temperature gradient over the course of 23 h. Metabolic rate and motor activity were significantly elevated in clorgyline-treated hamsters exposed to a Ta of 5 degrees C. There were no effects of clorgyline on evaporative water loss. In the temperature gradient the mean selected Ta of clorgyline-treated hamsters was nearly equal to that of the saline-treated hamsters, 30.7 and 31.2 degrees C, respectively. On the other hand, the mode of selected Ta in the clorgyline group was 2.8 degrees C higher than that of the saline group. Motor activity in the gradient was significantly elevated and food consumption was depressed by clorgyline treatment. Overall, these findings indicate that chronic clorgyline treatment in the golden hamster results in novel autonomic and behavioral modification; it stimulates metabolic thermogenesis during cold exposure, but appears to increase the behavioral zone of thermoneutrality. This latter effect may mean an improvement in heat tolerance, suggesting that this drug might assist in the adaptation to warm temperatures.

Animals↗
PubMed1993

Diurnal variations of serotonin and dopamine levels in discrete brain regions of Syrian hamsters and their modification by chronic clorgyline treatment.

In Syrian hamsters, chronic administration of the type A monoamine oxidase inhibitor, clorgyline (CLG), alters the intrinsic period and daily pattern of the circadian rhythm of wheel running, and changes the intensity-response curve for phase-shifting of the rhythm by light pulses. Chronic treatment with CLG also decreases hypothalamic and peritoneal temperatures, particularly during the rest phase of the activity-rest cycle. To help identify monoamines that may mediate CLG's effects on circadian rhythms, we measured levels of dopamine (DA) and serotonin (5-HT) at nine time points over a 24-h period in micro-dissected brain regions in chronic CLG-treated or saline-treated hamsters. For 5-HT, a diurnal variation was detected in all regions in saline-treated animals; for DA, no diurnal variation was detected in any region. In all regions, 5-HT levels and, to a lesser extent, DA levels were higher after CLG treatment. The acrophase of the 5-HT rhythm in the suprachiasmatic nucleus (SCN) was delayed by CLG-treatment, while the acrophase in the dorsal raphe nucleus was unchanged. The diurnal variation of 5-HT in the paraventricular nucleus of the hypothalamus, medial preoptic area, and median raphe nuclei was no longer detectable after chronic CLG-treatment. The phase-delay induced by CLG treatment in the daily rhythm of serotonin levels in the SCN, which functions as a circadian pacemaker, may be an important mechanism underlying the drug's capacity to slow the intrinsic rhythm of the pacemaker and to phase-delay behavioral rhythms that are under its control.

Animals↗
PubMed1992

Fluoxetine decreases brain temperature and REM sleep in Syrian hamsters.

The antidepressant drug, fluoxetine (FLX), a selective serotonin reuptake inhibitor, was administered to Syrian hamsters, and its acute and chronic effects on EEG sleep and hypothalamic temperature were recorded. Acute fluoxetine treatment at doses of 5, 10, 20 and 40 mg/kg decreased REM sleep and hypothalamic temperature in a dose-dependent manner. It increased NREM sleep, and, at doses of 20 and 40 mg/kg, it increased wakefulness. At 40 mg/kg, it decreased motor activity. During chronic treatment, tolerance developed to FLX's REM sleep-inhibiting effects, but tolerance did not develop to FLX's hypothalamic temperature-decreasing effects. Chronic FLX treatment produced circadian phase-dependent decreases in temperature beyond those that were observed during acute treatment. The apparent dissociation during chronic treatment between FLX's temperature-lowering effects and its REM-decreasing effects might be related to long-term changes in 5HT receptor function or FLX pharmacokinetics.

Animals↗
PubMed1991

Clorgyline-induced reduction in body temperature and its relationship to vigilance states in Syrian hamsters.

The antidepressant drug clorgyline, a monoamine oxidase inhibitor (MAOI) that selectively inhibits MAO type A was administered chronically to Syrian hamsters. Twenty-four-hour EEG sleep and/or telemetered peritoneal temperature were monitored during selected sampling periods over four weeks. Chronic clorgyline treatment decreased rapid-eye-movement (REM) sleep time and body temperature during the first week. Incomplete tolerance to these effects developed during the second and third weeks. REM sleep and body temperature were correlated during chronic clorgyline treatment. Non-REM (NREM) sleep was elevated throughout chronic treatment. These results suggest that clorgyline's effects on REM and NREM sleep might be related to clorgyline's effects on thermoregulation and to the development of tolerance. However, causal relationships between clorgyline's effects on thermoregulation and the levels of REM and NREM sleep remain to be determined.

Animals↗
PubMed1990

Cutaneous signs of internal disease in the elderly.

The elderly are prone to several systemic diseases that have their own particular cutaneous markers. These include pruritus, pigmentary changes, and the various manifestations associated with diabetes mellitus, among others. Physician recognition of the cutaneous signs of internal disorders will prompt early diagnosis and prompt treatment of the primary disease.

Aged↗
PubMed1989

Longitudinal sleep EEG, temperature, and activity measurements across the menstrual cycle in patients with premenstrual depression and in age-matched controls.

After a 2-month evaluation period, eight women with moderate to severe premenstrual depression and eight age- and sex-matched controls underwent sleep electroencephalographic (EEG) and temperature recordings 2 nights a week over the course of one menstrual cycle. Overall, patients had more Stage 2 (%) sleep and less rapid eye movement (REM) sleep (% and minutes) than normal controls. Stage 3 sleep and number of intermittent awakenings varied with phases of the menstrual cycle. Temperature minima were earlier in patients compared with controls, but this difference was not statistically significant, and there was no significant effect of menstrual cycle phase on the timing of temperature minima. Wrist motor activity did not change during the menstrual cycle in patients or controls. Thus, in this sample of women with premenstrual depression, we did not find sleep EEG alterations similar to those reported in some patients with major depressive disorder. In light of the small number of subjects and the large individual variability, the absence of marked changes with the menstrual cycle may be a function of a Type II error.

Adult↗
PubMed1989

Failure of erythromycin to cure secondary syphilis in a patient infected with the human immunodeficiency virus.

The case presented here involves a 32-year-old homosexual man with human immunodeficiency virus seropositivity and secondary syphilis. Because of possible penicillin allergy, he was initially treated with erythromycin base by mouth. During four weeks of therapy, his cutaneous lesions worsened as did his systemic symptoms. Following desensitization and parenteral penicillin therapy, his cutaneous lesions and symptoms rapidly resolved. His VDRL titer fell appropriately.

Adult↗
PubMed1988

Chronic clorgyline treatment of Syrian hamsters: an analysis of effects on the circadian pacemaker.

Clorgyline, a type A monoamine oxidase inhibitor with antidepressant properties when administered to depressed patients, is often associated with disturbances of the human sleep-wake cycle. In order to assess its effects on the mammalian circadian system, this drug was administered chronically to Syrian hamsters. It was found to affect the hamster circadian system in four specific ways. Clorgyline increased the intrinsic period of wheel-running activity, altered the phase response curve to brief light pulses, altered the reduced waveform of running activity in animals maintained in light-dark cycles or constant darkness, and increased the activity-rest ratio in animals maintained in constant darkness. Our data support the interpretation that clorgyline exhibits direct or indirect input to the circadian pacemaker and alters the processing of photic information to the pacemaker.

Animals↗