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Biomedical subjects

S Carroll

Publications and source records attributed to S Carroll.

At least 91 records · Page 5Linked to original sources
PubMed1992

The effects of cortisol infusion upon hormone secretion from the anterior pituitary and subjective mood in depressive illness and in controls.

The aims of this study were to determine whether the administration of cortisol has a significant effect on mood in patients with depression and whether the effects of cortisol on changes in plasma hormone concentrations are like those of synthetic corticosteroids. Twelve patients had major depression and one each had dysthymic disorder and a depressive adjustment disorder. Five were male and nine were female. All were in-patients. Eight normal subjects, two females and six males, were used as controls. Basal beta-endorphin concentrations were 2- to 3-fold higher in depressed patients than in control subjects, but there were no significant differences between the patient and control groups in the basal (pre-infusion) plasma concentrations of ACTH, cortisol, growth hormone or prolactin. Cortisol, but not saline infusion resulted in a significant improvement in self rated mood. Surprisingly, cortisol infusion at first increased plasma beta-endorphin concentrations. At later times after cortisol infusion, plasma beta-endorphin concentrations decreased as did the plasma concentrations of ACTH and growth hormone; prolactin levels were increased. These results show (i) that cortisol infusion raises mood significantly in major depression, (ii) that plasma beta-endorphin concentration is a potential marker of major depression (iii) that rather than blunting of corticosteroid effects, responses to cortisol may even be enhanced in depressive illness. The unexpected, initial increase in beta-endorphin stimulated by cortisol, suggests that the action of cortisol is not simply one of negative feedback inhibition, but may involve mineralocorticoid, as well as glucocorticoid receptors.

Adrenocorticotropic Hormone↗
PubMed1992

Lactation, nutrition and fertility and the secretion of prolactin and gonadotrophins in Mopan Mayan women.

The effect of lactation on menstrual cycles, ovulation and conception was studied in a group of non-contracepting Amerindian Mopan Mayan women. Anthropological observations of relevant events were made over a 21-month period. Blood samples were assayed to determine the plasma concentrations of prolactin, luteinising hormone, follicle stimulating hormone, human chorionic gonadotrophin, placental lactogen, oestrogen, progesterone and cortisol. The data show that: frequent and prolonged breast-feeding was associated with a marked increase in plasma prolactin concentrations to levels similar to those in lactating Gaing but higher than those in lactating Scottish women; ovulatory menstrual cycles and pregnancy occurred during frequent lactation; in lactating menstruating women there was an inverse correlation between fat weight and months post-partum. These data suggest that other factors as well as suckling account for the effects of lactation on fecundity.

Belize↗
PubMed1992

Atrial natriuretic peptide is involved in the ACTH response to stress and glucocorticoid negative feedback in the rat.

The role of atrial natriuretic peptide (ANP) in the ACTH response to stress and the glucocorticoid negative feedback control of ACTH release was investigated in adult male homozygous Brattleboro and adrenalectomized Wistar rats respectively, using the technique of immunoneutralization. The relatively low ACTH response to stress and the lack of arginine vasopressin make the homozygous Brattleboro rat a more rigorous and simpler preparation in which to test the hypothesis that ANP is involved in the ACTH response to stress. In both sets of experiments, blood sampling and injection of sheep anti-ANP or control serum were carried out in conscious animals through intra-atrial cannulae implanted 2 days previously under halothane anaesthesia. A 30-s exposure to ether resulted in a brisk twofold increase in the plasma ACTH concentrations in homozygous Brattleboro rats infused with anti-ANP, but not control serum. The injection of either dexamethasone, a potent glucocorticoid receptor agonist, or corticosterone resulted in a rapid and marked reduction in the plasma concentrations of ACTH in Wistar rats which had been adrenalectomized, under halothane anaesthesia, at least 21 days before experimentation. The inhibitory action of dexamethasone, but not corticosterone, was significantly reduced in animals infused with anti-ANP serum. These results show that the inhibition of ANP release into hypophysial portal blood is probably important for triggering the ACTH response to stress and that ANP may play a role in corticosteroid negative feedback control of ACTH release mediated by type II (glucocorticoid) receptors.

Adrenalectomy↗
PubMed1992

Nursing research priorities for the care of the naval hospital patient: a Delphi survey.

The purpose of this study was to identify priorities for nursing research in a naval hospital using the Delphi technique. A general objective was to provide empirically based information to guide the development of a nursing research program at a regional medical treatment facility. Via a three-round Delphi survey, priority research questions were identified for the nursing department of a naval regional medical treatment facility. A serendipitous result was the identification of nursing research priorities within a deployed naval fleet hospital.

Delphi Technique↗
PubMed1991

Endocytosis of immunotoxin-791T/36-RTA by tumor cells in relation to its cytotoxic action.

Ricin A chain immunotoxin constructed with monoclonal antibody 791T/36, which recognizes a tumor associated glycoprotein Mr 72,000 antigen present on sarcomas and colon and ovarian cancer cells, is cytotoxic for cell lines from tumors expressing this antigen. Incubation of sarcoma 791T cells with immunotoxin for only 5 min is sufficient to produce greater than 95% inhibition of tumor cell growth. Papain treatment of these cells to remove immunotoxin from the cell surface indicated that the cell surface acts as a reservoir for continued internalization of immunotoxin over several hours, but even so, 50% inhibition of cell survival was produced over a 2- to 3-h period. Analysis of the rate of endocytosis demonstrated that 30-50% of cell bound immunotoxin was internalized over a 180-min period. This was primarily dictated by the antibody moiety, regardless of the degree of conjugation to ricin A chain. This rate is much slower than that of other cell surface ligands such as transferrin. Cell cytosol acidification experiments were performed to determine whether this immunotoxin was internalized by clathrin coated pits, which is relatively rapid, or by smooth pits, which is slower, and the results indicated the latter mechanism is almost exclusively used. Intracellular trafficking of antibody 791T/36, conjugated to human serum albumin-tetramethylrhodamine was investigated by flow cytometry. The movement of the conjugate into the lysosomal compartment was delayed so that degradation products were only detected after a lag phase of 30-60 min. The lack of potentiator dependence of 791T/36 immunotoxin is in keeping with these findings.

Ammonium Chloride↗
PubMed1991

Interdependence of ryanodine binding, oligomeric receptor interactions, and Ca2+ release regulation in junctional sarcoplasmic reticulum.

We have examined ryanodine binding to its receptor (RR) and compared its effect on Ca2+ release to the Ca2+ release triggered by Ca2+ plus ATP, using vesicular fragments of junctional terminal cisternae (JTC) obtained from skeletal muscle. Ryanodine binding is slow (taking hours or days to complete) and is highly temperature (Q10 = 4) and Ca2+ dependent. At equilibrium, the extent of binding increases as the concentration of ryanodine is raised above 10(-9) M, exhibiting negative cooperativity and reaching the stoichiometry of the 560,000-Da RR chains near 10(-5) M ryanodine. The specificity of the high affinity binding is demonstrated by competitive binding of ryanodine analogs. Kinetic studies using rapid filtration show that, in the absence of ryanodine, rapid (k = 15 s-1) release of Ca2+ follows a triggering exposure of loaded JTC vesicles to perfusion media containing Ca2+ plus ATP. Induction of this release has no lag period and displays minimal temperature dependence. In contrast, prolonged exposure of JTC vesicles to low (10(-7) M) ryanodine concentrations changes the JTC to a state permitting slow (k = 1 s-1) release of Ca2+ even in the absence of the Ca2+ plus ATP trigger. Higher (greater than microM) concentrations of ryanodine do not allow any Ca2+ release and prevent even the release normally triggered by Ca2+ plus ATP. Our data suggest that ryanodine binds to the open state of the tetrameric RR, inducing protein conformational changes and altered oligomeric interactions. Binding of the first molecule of ryanodine to one of the four binding sites on the receptor produces a partially closed and low conductance state of the Ca2+ release channel and reduces the ryanodine binding affinity of the remaining sites. Ryanodine occupancy of all four binding sites on the receptor completes closure of the Ca2+ channel and blocks the triggering action of Ca2+ plus ATP. The tetrameric association of the RR chains is demonstrated by crosslinking with bifunctional reagents, generating crosslinked tetramers that retain ryanodine binding and Ca2+ release functions.

Adenosine Triphosphate↗
PubMed1991

Internalization of bacille Calmette-Guerin by bladder tumor cells.

Mechanisms by which intravesical bacille Calmette-Guerin (BCG) treatment mediates antitumor activity are currently poorly understood. We have determined that both human bladder tumor (T-24) and mouse bladder tumor (MBT-2) cells are capable of internalizing the BCG and have characterized this process in vitro. The internalization of BCG by T-24 and MBT-2 cells was verified by histochemistry and electron microscopy. Time dependent internalization of BCG was observed with a maximum occurring at three hrs. Internalization was significantly inhibited by both incubation at 4C and cytochalasin B; conditions known to inhibit phagocytosis. Ultrastructural studies suggested that BCG were transported to membrane bound intracellular compartments and were degraded. The compartments containing the degraded mycobacteria labeled with the fluid phase marker HRP which is known to be transported to lysosomes in a variety of cell types. To determine if the internalization process occurred in vivo, we examined bladder washings of patients treated with intravesical BCG. The majority of the cells in the bladder washings were inflammatory cells which contained ingested BCG. In addition, internalized and degraded BCG were identified in urothelial cells. These data demonstrate that BCG are internalized by transitional epithelial cells both in vitro and in vivo. The internalization process is inhibitable by temperature and microfilament disruption. The potential therapeutic implications of this process and its relationship to antitumor activity of BCG therapy are currently being investigated.

Actin Cytoskeleton↗
PubMed1991

Psychological, hormonal and biochemical changes following carbohydrate bingeing: a placebo controlled study in bulimia nervosa and matched controls.

The responses of thirteen patients with bulimia nervosa and sixteen controls matched for age and weight are described following the ingestion of a carbohydrate and a calorie-free placebo mixture in simulated binges. Psychological, hormonal and biochemical parameters were measured before and at 15 minute intervals for two hours after the simulated binge. At baseline, the bulimics were clearly more symptomatic than the controls. The control population showed a specific satiating effect of carbohydrate upon hunger ratings. Bulimic patients responded differently showing a blunting of the normal sensation of hunger and an enhanced rating for nausea. Prolactin, growth hormone (GH) and cortisol failed to show a carbohydrate-mediated stimulation in either population. The bulimic patients showed a different pattern of GH release, but this was independent of the challenge condition. Large neutral amino acid (LNAA) levels fell following carbohydrate ingestion, but produced an increase of up to 20% in the tryptophan: LNAA ratio in both bulimic patients and the control group. Thus, while this increase in tryptophan availability failed to provoke hormone release, the time course of the carbohydrate specific effect on the sensations of hunger and nausea is compatible with a mechanism based on increased tryptophan availability. The confusion of satiety with nausea may provide a useful focus for the future treatment of patients with bulimia nervosa.

Adult↗
PubMed1991

Atrial natriuretic peptide is a physiological inhibitor of ACTH release: evidence from immunoneutralization in vivo.

The brain is thought to exert a predominantly stimulatory action on ACTH secretion mediated mainly by corticotrophin-releasing factor-41 (CRF-41) and arginine vasopressin (AVP). Several data, however, also point to the existence of an ACTH-inhibiting factor. Atrial natriuretic peptide (ANP), at concentrations found in hypophysial portal blood, inhibits ACTH release in vitro. The aim of the present studies was to use ANP immunoneutralization to determine whether ANP does in fact inhibit ACTH release in vivo. Intracerebroventricular infusion (1 microliters/min for 30 min) of sheep anti-ANP serum into male rats anaesthetized with sodium pentobarbitone had no significant effect on jugular venous plasma concentrations of ACTH or LH but did decrease significantly the plasma concentrations of prolactin. Intravenous infusion of 0.8 ml sheep anti-ANP serum but not control (non-immune) sheep serum, through an indwelling intra-atrial cannula in conscious male rats resulted in a marked and significant increase in plasma ACTH and corticosterone concentrations. The ACTH and corticosterone response to a 30-s ether stress was not significantly potentiated in the same conscious rats infused with anti-ANP serum. Intra-atrial infusion of anti-ANP did not significantly affect plasma prolactin, LH, glucose or sodium concentrations or plasma osmolality. These results show for the first time that ANP is a potent inhibitor of ACTH secretion in the conscious male rat and that, therefore, ANP is a hypothalamic neurohormone which is likely to play an important inhibitory role in the neural control of ACTH release.

Adrenocorticotropic Hormone↗
PubMed1990

A computer model of antenatal care: relationship between the distribution of obstetric risk factors in simulated cases and in a real population.

The main purpose of antenatal care is to identify risk factors for the fetus. A number of systems have been described in which positive factors are summed to produce an overall risk score for the individual woman. In the present study a computer simulation of a population of pregnant women has been used to examine the use of Bayes theorem to calculate obstetric risk scores. The findings of the computer simulation have been compared with those in a real obstetric population (774 primigravidae; 930 multigravidae). A number of observations have been made which may be of considerable practical significance: (1) in the population as a whole the distribution of risk scores is skewed; most women have a low score while relatively few subjects have high scores; (2) a minimum number of risk factors must be present simultaneously for the risk in an individual to consistently exceed the overall population risk; this number is 4 in primigravidae and 5 in multigravidae; (3) the relationship between the number of risk factors and overall risk does not follow a straight line. The computer simulation provides a test bed in which various assumptions can be examined, such as the effect of removing or redefining given risk factors.

Bayes Theorem↗
PubMed1990

Reduced plasma oestrogen stimulated neurophysin and delayed response to oestrogen challenge in Alzheimer's disease.

Plasma concentrations of oestrogen stimulated neurophysin (ESN) were reduced in 28 patients with Alzheimer's disease (AD) compared with 14 age-matched controls, 16 patients with other presenile dementias and 12 patients with major depressive disorder. The ESN response to oestrogen challenge was delayed in 10 AD patients compared with 7 age-matched controls. Reduced basal and oestrogen stimulated plasma ESN may be related to impaired responsiveness of the hypothalamo-neurohypophysial neurons and/or a reduction in the amount of pituitary ESN available for release. Plasma ESN measurements may be of value for excluding the diagnosis of AD in patients with dementia who present before the age of 65.

Administration, Oral↗
PubMed1990

A comparison of different methods for calculating overall risk scores from risk factors ascertained in a computerized obstetric information system.

Current obstetric risk-scoring systems depend upon simple addition of weighted or unweighted risk factors. In this study a population of 994 pregnant women (470 primiparae; 524 multiparae) has been examined in order to compare the use of weighted and unweighted risk scores, together with Bayes theorem, in estimating an overall risk score from the presence of individual risk factors. The findings have been related to fetal outcome in these pregnancies and expressed as receiver-operating characteristic (ROC) curves for different cutoff levels between normal and abnormal. In primiparae, the use of weighted risk factors, with or without Bayes theorem, was clearly superior to the use of unweighted factors. In multiparae there was only a marginal difference between the three approaches. The increasing use of computerised information system in antenatal care should make calculation of risk scores for every pregnant woman a practical option.

Adolescent↗
PubMed1989

The neuroendocrine responses and psychological effects of infusion of L-tryptophan in anorexia nervosa.

The secretion of prolactin and growth hormone (GH), together with subjective ratings of sedation and hunger, were determined in 13 in-patients with anorexia nervosa and 15 controls during the intravenous infusion of L-tryptophan (100 mg/kg). Prolactin responses were not different between groups but GH responses were markedly blunted in patients. In addition sedation responses in patients were attenuated compared with controls. Hunger ratings were reduced by the infusion in controls but were too variable to be interpreted in the patients. Plasma amino acid levels were also determined before and after infusion of L-tryptophan. Tryptophan levels were comparable in the two groups as were the levels of tyrosine, phenyl alanine, valine, leucine and iso-leucine. The results suggest that some aspects of 5-hydroxytryptamine function may be attenuated in anorexia nervosa. However, they undoubtedly contrast with the finding of enhanced hormonal responses in acute dieting and may be relevant to the interpretation of similar experiments in depressive illness.

Adult↗
PubMed1989

Luteinizing hormone responses to luteinizing hormone releasing hormone (LHRH) in acute mania and the effects of lithium on LHRH and thyrotrophin releasing hormone tests in volunteers.

The endocrine responses to Luteinizing Hormone Releasing Hormone (LHRH) of eight drug-free males with mania were determined. Basal levels of Luteinizing Hormone (LH) and the plasma levels following injection of LHRH were elevated in patients compared with controls; Follicle Stimulating Hormone (FSH) and testosterone were not different. Elevated levels of LH have been described previously in recovered manic patients and have been suggested to be state-independent features of mania. In order to clarify the status of this finding, the effects of lithium administration upon hormone responses to LHRH in six male volunteers were also investigated, together with the effects upon Thyrotrophin Releasing Hormone (TRH) stimulation of Thyroid Stimulating Hormone (TSH) and prolactin release. Lithium increased the basal levels of LH and levels after injection of LHRH without effect upon FSH and testosterone. Lithium also increased basal and TRH stimulated release of TSH and basal prolactin levels. Lithium was without effect upon prolactin responses to TRH. The results are discussed in relation to current information on the mechanism of lithium's action. The implications for neuroendocrine work on recovered patients taking lithium are also explored.

Adult↗
PubMed1989

Intestinal surfactant-like material. A novel secretory product of the rat enterocyte.

Surface-active phospholipid-containing particles are traditionally considered to be the product of type II pneumocytes. We now demonstrate membrane-bound lamellar cytoplasmic organelles in adult and suckling rat enterocytes that are densely reactive with phospholipid-staining reagents. These structures were seen in the basolateral space, within the intercellular junctions, and unraveling on the lumenal surface, and were more abundant after fat feeding. Light scrapings of intestinal mucosa and lumenal washings that contained these bodies, as evidenced by morphology and biochemical analysis, lowered surface tension in a pulsating bubble assay. Production by normal enterocytes of material with surfactant-like appearance and properties demonstrates that these structures are present in extrapulmonary epithelia, and extends the possible range of their function beyond gaseous exchange, e.g., solute exchange or lubrication on membrane surfaces.

Acid Phosphatase↗
PubMed1988

Regulation of pituitary alpha-subunit, beta-luteinizing hormone and prolactin messenger ribonucleic acid by gonadotropin-releasing hormone and estradiol in hypogonadal mice.

We have investigated the effects of three different GnRH injection regimens and the effects of estradiol benzoate (EB) on expression of the common alpha-subunit, beta-LH, and PRL genes in male and female hpg mice. GnRH was injected once daily (100 ng), every 2 h (100 ng) or every 30 min (25 ng), and EB (10 micrograms) was injected once daily. The effects of continuous exposure to the superactive agonist D-Trp6-GnRH released from microcapsules were also studied. Northern blot analysis showed that administration of GnRH increased alpha-subunit mRNA levels 2- to 10-fold in male and female hpg but not normal mice and had no significant effect on beta-LH or beta-TSH mRNA levels. The greatest increase in alpha-mRNA occurred when 100 ng GnRH were injected every 2 h and could be detected within 6 h of the first GnRH injection. More frequent injections (25 ng every 30 min) were less effective in increasing alpha-mRNA, as was prolonged exposure to the D-Trp6-GnRH superagonist. The increase in alpha-mRNA was associated with an increase in pituitary FSH content of similar magnitude. Continuous exposure of the pituitary gland to D-Trp6-GnRH (approximately 1500 ng/day) resulted in a smaller (2-fold) increase in alpha-mRNA and pituitary FSH content, suggesting that desensitization had occurred. EB had little effect on beta-LH mRNA and did not alter alpha-mRNA levels or affect the increase in alpha-mRNA caused by GnRH. Injection of GnRH every 2 h increased pituitary PRL mRNA levels in female but not male hpg mice, probably due to an indirect effect resulting from increased estrogen secretion. We conclude that GnRH administration to hpg mice significantly increases alpha-subunit but not beta-LH mRNA levels and that maximal effects occur with 100 ng GnRH injections every 2 h. Although EB does have direct effects upon pituitary gonadotropin content in hpg mice, the absence of significant changes in alpha- and beta-LH mRNA suggests that these effects may be largely posttranscriptional.

Animals↗
PubMed1984

Speech, admittance and tone tests in school screening. Reconciling economics with pathology and disability perspectives.

In theory a criterion can be set on any test score to 'pass' or 'fail' a desired percentage of any population; but in practice, particular measures used in screening can have both intrinsically appropriate criteria and zones of great uncertainty in relation to the condition being screened. For example, the criteria for possible abnormality on oto-admittance measures in single-test screening for middle ear disease are intrinsically rather too sensitive, as potentially pathological signs are displayed by a high proportion of the population. In contrast, criteria on pure tone measures are intrinsically insensitive. One solution to such dilemmas and to other deficiencies of screening lies in a two-test approach. In two investigations we have examined these accepted screening tests in relation to a proposal to introduce also a disability measure as a means of broadening the information available from school screening systems and reducing over-referral from oto-admittance screening. A minimal-pair monosyllable 2-alternative forced-choice speech-in-noise test with a picture-pointing identification response was developed and refined. The results obtained usefully complement existing screening methods and we examine ways of combining them with either pure tone threshold of oto-admittance measures. A sequential set of criteria for passing, referral or continuation of testing allows the test to be applied in short form for those children failing a pre-screen at a stringent level. In this way a reduction of approximately 10% of the total screened sample is obtained in the number of children needing referral or re-testing; the total testing time need not increase substantially; and more precise disability information is obtained on the marginal cases, where it is needed. Multiple regression enables a severity index (on the same scale as the widely appreciated pure-tone threshold scale) to be derived from speech and oto-admittance measures jointly. An adequate basis of referral for medical assessment and treatment of pathology would still require admittance methods at some stage, whatever the drawbacks may be in their sole use as a screen. The two-test sequential approach reconciles the pathology perspective and the disability perspective.

Acoustic Impedance Tests↗