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Biomedical subjects

C C Taylor

Publications and source records attributed to C C Taylor.

At least 37 records · Page 2Linked to original sources
PubMed1997

Dynorphin A1-13 stimulates ovine fetal pituitary-adrenal function through a novel nonopioid mechanism.

We previously reported that U50488H, a kappa-selective opioid agonist, stimulates the release of adrenocorticotropin (ACTH) in the ovine fetus via the release of hypothalamic arginine vasopressin and corticotropin releasing factor. In this study we examined the effects of the endogenous kappa-preferring opioid peptide, dynorphin A1-13, on fetal ACTH release using the unanesthetized, chronically catheterized fetal lamb model. Fetal plasma samples were collected at timed intervals after fetal administration of dynorphin A1-13 (0.5 mg/kg, i.v.) and subsequently analyzed by radioimmunoassay for immunoreactive-ACTH and immunoreactive-cortisol. Dynorphin A1-13 produced a highly significant and rapid increase in immunoreactive-ACTH (P = .002) and immunoreactive-cortisol (P = .002) with peak levels of 383.3 +/- 43.8 pg/ml and 32.8 +/- 9.0 ng/ml, respectively, at 15 min after administration. A similar increase in plasma immunoreactive-ACTH was seen after the same dose of dynorphin A1-17 (P = .02) but not dynorphin A2-17. This ACTH response to dynorphin A1-13 was shown to be insensitive to the opioid antagonist, naloxone (12 mg/hr), as well as antagonists of corticotropin releasing factor and arginine vasopressin. These data suggest that dynorphin A1-13 in the ovine fetus may be acting through a mechanism distinct from the kappa-opioid system and that the dynorphins may serve as secretagogues of ACTH directly at the anterior pituitary through nonopioid receptors.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1997

Opioid modulation of the fetal hypothalamic-pituitary-adrenal axis: the role of receptor subtypes and route of administration.

The role of receptor subtypes in opioid modulation of the hypothalamic-pituitary-adrenal (HPA) axis is well understood in the adult but has not been investigated in the developing fetus. Because the fetal HPA axis plays an important role in the development of several vital organs and in the onset of parturition, an understanding of the role of opioid receptor subtypes on the fetal HPA axis is important in the design of new obstetrical analgesics. In these studies, we examined the effects of highly selective mu, delta and kappa opioid agonists on plasma immunoreactive adrenocorticotropin (ir-ACTH) and immunoreactive cortisol (ir-cortisol) in the ovine fetus. Intravenous administration of the mu selective agonist [D-Ala2-N-Me-Phe4,Gly-ol]-enkephalin resulted in a 92% increase in ir-ACTH (P = .005) and ir-cortisol. The delta selective agonist, [D-Pen2,D-Pen5]-enkephalin, elicited a much smaller increase (52%) in ir-ACTH (P = .01). In contrast, there was a 7-fold increase in ir-ACTH (P < .001) and a significant increase in ir-cortisol (P = .02) with the kappa selective U50,488H. When the same agonists were administered intracerebroventricularly, there was no change in ir-ACTH or ir-cortisol. These data suggest that the kappa opioid receptor may be more important in the modulation of the fetal HPA axis and that the distribution of these opioid agonists from the lateral ventricle to the hypothalamus and pituitary is very limited.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1996

Cardiovascular and respiratory actions of U50,488H in the unanaesthetized ovine foetus.

In an effort to evaluate the feasibility of kappa-opioid receptor agonists for use in pregnancy, we have investigated the actions of U50,488H (trans-3,4-dichloro-N-methyl-N-[2-(1- pyrrolidinyl)cyclohexyl]benzeneacetamide) on cardiovascular and respiratory control in the unanaesthetized ovine foetus. Intravenous administration of U50,488H (1.0 mg/kg) to the foetus resulted in an immediate increase in foetal blood pressure (P < 0.0001) and heart rate (P < 0.0001) which lasted 15 min, followed by a prolonged loss of heart rate variability for up to 3 h. There was also a significant suppression of foetal breathing movements for 2-3 h (P < 0.008). Pretreatment with naloxone (12 mg/h) completely blocked the hypertensive and tachycardiac response to U50,488H, but was unable to prevent the loss of variation in heart rate or respiratory depression. These data suggest that U50,488H can exert direct cardiovascular and respiratory actions in the ovine foetus via both opioid and non-opioid mechanisms. The naloxone-insensitive suppression of foetal breathing would severely limit the use of U50,488H as an obstetrical analgesic.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1996

A functional-analytic approach to the diagnosis of a transient tic disorder.

The diagnostic utility of functional analyses has been demonstrated with a variety of behaviors including tics. Whereas previous analyses have focused on the discovery of maintaining variables to aid in treatment prescription, we employed a functional analysis to confirm a clinical diagnosis. An 11 year old male student, who had not been previously diagnosed with a tic disorder, exhibited multiple vocal tic-like behaviors which had persisted over a period of time. Teacher reports conflicted regarding the possible etiology of these behaviors. Hence, a functional analysis was conducted in the classroom to determine if the behaviors were maintained by operant variables. Our hypothesis stated that the occurrence of vocal behaviors across experimental conditions would strongly indicate the presence of a tic disorder. The functional analysis included the following conditions: attention, escape, alone, freeplay, and high sensory stimulation. We used a multi-element design to evaluate the effects of the different stimulus conditions on vocal-behavior frequency. Data indicated the student exhibited vocal behaviors in all conditions. However, the behaviors were partially exacerbated in the attention and escape conditions. Results supported the diagnosis of a transient tic disorder affected by operant variables.

Attention↗
PubMed1996

Lipopolysaccharide inhibits in vitro luteinizing hormone-stimulated rat ovarian granulosa cell estradiol but not progesterone secretion.

Endotoxin, known as lipopolysaccharide (LPS), is a component of gram-negative bacterial cell walls and is a potent immunostimulator, inducing the release of several cytokines, such as tumor necrosis factor alpha (TNF alpha) and interleukins (IL) 1, 6, and 8. A previous study with immature rats revealed that exogenous administration of LPS inhibits ovarian estradiol secretion in response to eCG. The present study was undertaken in order to determine whether LPS could directly inhibit rat granulosa cell (GC) steroid secretion. GC were collected and purified from 26-day-old hypophysectomized female rats (hypophysectomy on Day 23). Purified GC were highly responsive to FSH (1-100 ng/ml), leading to increased estradiol, progesterone, and cAMP accumulation in culture media. GC were also capable of binding 125I-labeled hCG and were responsive to LH stimulation. Treatment of GC with LPS (1-100 ng/ml) led to a significant (p < 0.01) dose-dependent decrease in LH-stimulated estradiol accumulation in culture media (maximum 75% inhibition). However, treatment of GC with LPS had no significant effect on FSH-stimulated progesterone or estradiol, or LH-stimulated progesterone accumulation in culture media. GC stimulated with 8-bromo cAMP were also insensitive to the effects of LPS. LPS had no significant effect on 125I-labeled hCG binding to GC homogenates, nor did it have any significant effect on FSH or LH-stimulated cAMP accumulation. Treatment of both FSH and LH-stimulated GC with LPS was associated with an increase in IL-6 bioactivity in culture media. This effect could be blocked with the nonreceptor tyrosine kinase inhibitor herbimycin A. TNF alpha bioactivity was undetectable with or without LPS challenge. Direct challenge of GC with recombinant murine IL-6 had no effect on either FSH or LH-stimulated estradiol whereas TNF alpha inhibited FSH-stimulated estradiol secretion. Collectively, these results suggest that the inhibitory effects of LPS were not mediated by either IL-6 or TNF alpha. Treatment of GC with the epidermal growth factor receptor tyrosine kinase inhibitor, tyrphostin A46, blocked the inhibitory effects of LPS on steroid secretion and was associated with an increased cAMP accumulation in culture media. The results indicate that LPS inhibits in vitro GC estradiol secretion. This effect appears to be restricted to the LH-stimulated aromatization of androgens to estrogen and may involve a tyrosine kinase signaling pathway.

Animals↗
PubMed1996

Differential mechanisms of ovine fetal pituitary stimulation by a selective kappa-opioid agonist and by dynorphin.

Dynorphin has long been considered the putative endogenous ligand for the kappa-opioid receptor. The high density of kappa-opioid receptors in the hypothalamus and the high concentration of dynorphin peptides in the pituitary suggest that they may play an important role in regulation of the hypothalamic-pituitary-adrenal (HPA) axis. To investigate this possibility in early development, we examined the effects of a highly selective kappa-opioid agonist, U50488H (trans- (+/-)-3,4-dichloro-N-methyl-[2-(1-pyrrolidinyl)-cyclohexyl] benzeneacetamide) and dynorphin A1-13 on plasma immunoreactive adrenocorticotropin (ir-ACTH) in the ovine fetus. Although both U50488H (1.0 mg/kg i.v.) and dynorphin A1-13 (0.5 mg/kg i.v.) evoked a similar robust increase in ir-ACTH levels, the response to dynorphin A1-13 peaked at 15 min while the maximal response to U50488H was not seen until 60 min following administration. In addition, the response to dynorphin A1-13, but not U50488H, was dependent upon the gestational age of the fetus. The response to U50488H was blocked by naloxone as well as antagonists of AVP and CRF indicating that U50488H is eliciting its effects via opioid receptors, most likely of the kappa receptor subtype, at the hypothalamus. Conversely, the dynorphin A1-13 response was not blocked by any of the aforementioned antagonist. Thus, it appears that dynorphin A1-13 may act as a direct mediator of ACTH release via nonopioid receptors at the level of the pituitary.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1996

Src tyrosine kinase activity is related to luteinizing hormone responsiveness: genetic manipulations using mouse MA10 Leydig cells.

The Src family of tyrosine kinases play an important role in various signal transduction pathways in many different cell types, however, the role of these kinases in steroidogenic cells has not been examined. In the present study, genetic approaches were used to directly alter Src tyrosine kinase activity in mouse MA10 Leydig cells in order to determine the effect of changes of Src activity on LH-responsiveness with regard to cAMP and progesterone secretion. MA10 cells expressing a dominant negative Src (MA10(Srck-3)) secreted more cAMP and progesterone in response to LH than control transfected cells. Phosphodiesterase activity was decreased in MA10(Srck-3) cells. Conversely, MA10 cells expressing a temperature sensitive Src (MA10(tsUP)) lost LH-responsiveness with regard to cAMP and progesterone secretion at the Src active temperature (35 degrees C). It is concluded that Src tyrosine kinase has an important role in regulating steroid secretion in MA10 Leydig cells. This regulation may in part be due to Src modulation of phosphodiesterase activity, although other components of the LH-signaling pathway may be involved.

Animals↗
PubMed1996

kappa-Opioid agonist, U50,488H, stimulates ovine fetal pituitary-adrenal function via hypothalamic arginine-vasopressin and corticotrophin-releasing factor.

The fetal hypothalamic-pituitary-adrenal axis is regulated by such factors as corticotrophin releasing factor, arginine vasopressin and the endogenous opioid peptides. The goal of this study was to determine whether activation of the kappa-opioid system can modulate ovine fetal pituitary-adrenal function. The highly selective kappa-opioid agonist, U50,488H ¿trans-(+/-)-3, 4-dichloro-N-methyl-[2-(1-pyrrolidinyl)-cyclohexy]benzeneacetamide ¿ (1 mg/kg, i.v.), was administered directly to the ovine fetus in utero and fetal plasma levels of immunoreactive adrenocorticotrophin (ir-ACTH) and cortisol (ir-cortisol) were measured via radioimmunoassay. U50,488H resulted in an immediate and highly significant (P = .00005) increase in ir-ACTH, with a concomitant, significant (P = .02) increase in ir-cortisol. The peak increase was 312.1 +/- 31.2 pg/ml and 17.9 +/- 5.4 ng/ml from predrug control values for ir-ACTH and ir-cortisol, respectively, at 60 min after administration of U50,488H. This stimulation was completely blocked by concurrent naloxone (12 mg/hr, i.v.) administration, indicating that U50,488H is acting at classical opioid receptors to elicit this effect. Pretreatment with antagonists of arginine vasopressin or corticotrophin releasing factor attenuated the U50,488H response and it was therefore concluded that U50,488H is most likely acting to modulate ir-ACTH and ir-cortisol levels through regulation of arginine vasopressin and corticotrophin releasing factor release via hypothalamic kappa-opioid receptors. The results of this study should aid in the design of obstetrical analgesics that will not alter the fetal stress response.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1995

Lipopolysaccharide inhibits rat ovarian thecal-interstitial cell steroid secretion in vitro.

Lipopolysaccharide (LPS), a major component of gram-negative cell walls, is a potent immunostimulator. Treatment of monocytes/macrophages in vitro with LPS induces the secretion of cytokines such as tumor necrosis factor-alpha and interleukin-1 alpha, -1 beta, and -6. LPS is thought to require LPS-binding protein or CD14 to act at low concentrations (< 100 ng LPS/ml). In the present study, rat ovarian thecal-interstitial cells (TIC) were cultured in a serum-free culture system (in the absence of LPS-binding protein or soluble CD14) and challenged with LPS. Treatment with LPS led to a dose-dependent (1-100 ng LPS/ml) decrease in LH-stimulated progesterone and androstenedione secretion. LPS had no effect on radiolabeled hCG binding to TIC homogenates or cAMP accumulation in culture medium. LPS treatment was associated with an increase in interleukin-6 bioactivity in the medium of thecal-interstitial cell cultures; however, tumor necrosis factor-alpha bioactivity was undetectable. Herbimycin A, an src tyrosine kinase inhibitor, blocked the actions of LPS and was associated with an increase in cAMP accumulation in TIC culture medium. The results suggest that LPS can act directly on ovarian thecal-interstitial cells and that this can occur in a LPS-binding protein/CD14-independent manner. The actions of LPS appear to be specific and require a nonreceptor tyrosine kinase.

Androstenedione↗
PubMed1992

Growth and development of human muscle: a quantitative morphological study of whole vastus lateralis from childhood to adult age.

The mechanisms underlying the increase in volume of muscle tissue, and the functional development of muscle fibers from childhood through adolescence to adult age, have been studied. Cross sections of autopsied whole vastus lateralis muscle from 22 previously physically healthy males, 5 to 37 years of age, were prepared enzyme histochemically (myofibrillar ATPase) and examined morphometrically. The data obtained on muscle cross-sectional area, size, total number, and proportion of type 1 (slow-twitch) and type 2 (fast-twitch) fibers were analyzed using linear regression techniques. The results show that the increase in muscle cross-sectional area from childhood to adult age is caused by an increase in mean fiber size. This is accompanied by a functional development of the fiber population: the proportion of type 2 fibers increases significantly from the age of 5 (approx. 35%) to the age of 20 (approx. 50%), which, in the absence of any discernible effect on the total number of fibers, is most likely caused by a transformation of type 1 to type 2 fibers.

Adolescent↗
PubMed1991

Evidence of fibre hyperplasia in human skeletal muscles from healthy young men? A left-right comparison of the fibre number in whole anterior tibialis muscles.

Cross-sections (thickness 10 microns) of whole autopsied left and right anterior tibialis muscles of seven young previously healthy right-handed men (mean age 23 years, range 18-32 years) were prepared for light-microscope enzyme histochemistry. Muscle cross-sectional area and total number of fibres, mean fibre size (indirectly determined) and proportion of the different fibre types (type 1 and type 2 on basis of myofibrillar adenosine triphosphatase characteristics), in each muscle cross-section were determined. The analysis showed that the cross-sectional area of the left muscle was significantly larger (P less than 0.05), and the total number of fibres was significantly higher (P less than 0.05), than for the corresponding right muscle. There was no significant difference for the mean fibre size or the proportion of the two fibre types. The results imply that long-term asymmetrical low-level daily demands on muscles of the left and the right lower leg in right-handed individuals provide enough stimuli to induce an enlargement of the muscles on the left side, and that this enlargement is due to an increase in the number of muscle fibres (fibre hyperplasia). Calculations based on the data also explain why the underlying process of hyperplasia is difficult, or even impossible, to detect in standard muscle biopsies.

Adaptation, Physiological↗
PubMed1991

A morphometrical comparison of right and left whole human vastus lateralis muscle: how to reduce sampling errors in biopsy techniques.

In studies of the effects of different training programmes, one muscle--most commonly the vastus lateralis--is used for the experiment while the contralateral muscle serves as a control, at the same time as muscle biopsies are taken from both sides. In order to increase the reliability of such studies, the sources and the magnitude of the sampling errors in the biopsy techniques need to be assessed in detail. In this study, cross-sections of whole right and left vastus lateralis muscle from six young sedentary right-handed men were prepared, and the total number and size of fibres and the proportion of the different fibre types were calculated. A significant difference (P less than 0.05-P less than 0.001) between the right and the left muscle was found for at least one of the three variables in each of the six men, but there was no systematic difference and, therefore, no significant right-left difference for the whole group. The maximum difference between the right and the left side for the mean fibre size was 25% and for the fibre type proportion 5%; these differences are much smaller than the known variation within individual muscles. In conclusion, any study involving biopsies from both the right and the left vastus lateralis may use either muscle for the experiment while the contralateral muscle serves as a control without leading to systematic sampling error, whereas the errors involved in taking small samples from each muscle are much more important to control and to reduce.

Adult↗
PubMed1991

Variability in muscle fibre areas in whole human quadriceps muscle: effects of increasing age.

Cross-sections of whole vastus lateralis muscle from 20 men, 19 to 84 years of age, were prepared, and the cross-sectional area (microns2) of 375 type 1 and 375 Type 2 fibres was measured in five different regions throughout each muscle. In muscles from the old individuals, the mean CSA of Type 2 fibres was on average nearly 35% smaller (P less than 0.001) while the mean CSA of Type 1 fibres was on average just over 6% smaller (NS) than in muscles from the young individuals. There was a highly significant (P less than 0.001) variation in the mean CSA of both fibre types within all muscles. In the old muscles, there was no significant difference in mean fibre CSA between deep and superficial parts while in the young muscles the mean fibre CSA was significantly (P less than 0.05) larger in deep regions than superficially. The range of the fibre CSA was larger in the old muscles with an increased number of both hypotrophied and atrophied fibres as well as large, sometimes very large, fibres. The standard deviation of the fibre CSA of Type 2 fibres was significantly (P less than 0.001) larger than for Type 1 fibres in 60% of the regions of the old muscles compared to 12.5% of the regions of the young muscles, but the standard deviation for the whole muscles was more or less unaffected with increasing age. In the old age group, there were fewer muscles and regions with a correlation between the CSA of Type 1 and Type 2 fibres than in the young age group. In conclusion the age-related changes in the mean fibre CSA, and in the pattern of variation in fibre CSA throughout the muscle and in small sample regions, suggest a combination of a progressive denervation process and an altered physical activity level as the two major mechanisms underlying the effects of normal development and ageing on the human vastus lateralis muscle.

Adult↗
PubMed1990

Condoms and cosmology: the 'fractal' person and sexual risk in Rwanda.

While condoms are readily available in the urban centers of Rwanda, where the AIDS epidemic has ranged most intensely, researchers report that women are reluctant to have their partners use them. When asked to explain their reluctance, these women express the fear (along with other misgivings) that the condom might remain lodged in the vagina after intercourse. This behavior flies in the face of the biomedical assessment of risk. Rwandans, however, perceive risk in a manner which is consistent with their views concerning the social construction of the moral person. Of prime importance in this process is the body's perceived aptitude to engage in meaningful exchange and fertile sexuality. Moreover, these notions take root within a coherent cosmological matrix which emphasizes the socially ordered flow of fertility fluids. Only when these issues are considered in light of the concept of the 'fractal person' does the meaning of risk--as it relates to sexual behavior and AIDS in Rwanda--become clear.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Variability in muscle fibre areas in whole human quadriceps muscle: how to reduce sampling errors in biopsy techniques.

A single biopsy is a poor estimator of the muscle fibre cross-sectional area (CSA) for a whole human muscle because of the large variability in the fibre area within a muscle. To determine how the sampling errors in biopsy techniques can be reduced, data on the CSA of type 1 and type 2 fibres obtained from cross-sections of whole vastus lateralis muscle of young men, have been analysed statistically. To obtain a good estimate of the mean fibre CSA in a biopsy, measuring all fibres in that biopsy gives the best result. To obtain a good estimate of the mean fibre CSA for a whole muscle, the number of biopsies has a much greater influence on the sampling error than the number of fibres measured in each biopsy, but the number of biopsies needed to obtain a given sampling error can vary by a factor of two. If the fibre CSA in three or more biopsies is measured, it is sufficient to measure only 25 fibres in each biopsy. If less than three biopsies are taken, there is no worthwhile reduction in sampling error when more than 100 fibres are measured. To determine the mean fibre CSA for a whole group of individuals, our preference is to maximize the number of individuals, and only take single biopsies. In conclusion, to determine the mean fibre CSA for this particular muscle with a certain precision, we suggest analysis of three biopsies, taken from different depths of the muscle, and measurement of 25 fibres in each biopsy.

Adolescent↗
PubMed1989

Variability in muscle fibre areas in whole human quadriceps muscle. How much and why?

To determine the variability in fibre areas in the human vastus lateralis muscle, cross-sections (15 microns) of whole autopsied muscles from eight young men have been prepared, and the cross-sectional area (CSA) of 375 type 1 and 375 type 2 fibres has been measured in five different regions throughout each muscle. The CSA of both fibre types varied significantly within all muscle cross-sections. Fibres in the deep parts of the muscle were larger than superficially. There was a significant correlation between the CSA of the two fibre types within each region: if a fibre of a given type was small, or large, the other fibre type was also small, or large. The CSA of type 2 fibres was larger than the CSA of type 1 fibres in 26 of the 40 regions: regions with type 1 fibres larger than type 2 fibres were mostly (71%) found deep in the muscle. The standard deviation of the CSA of type 1 fibres was significantly larger than for type 2 fibres in 35 of the 40 regions. In conclusion, the CSA of the different fibre types in the vastus lateralis of young men varies non-randomly. The pattern of variation, both throughout the muscle and in small sample regions, supports the general opinion that the functional demands placed on the fibre population are an important factor in the development of the fibre properties.

Adenosine Triphosphatases↗
PubMed1988

What is the cause of the ageing atrophy? Total number, size and proportion of different fiber types studied in whole vastus lateralis muscle from 15- to 83-year-old men.

In order to study the effects of increasing age on the human skeletal muscle, cross-sections (15 micron) of autopsied whole vastus lateralis muscle from 43 previously physically healthy men between 15 and 83 years of age were prepared and examined. The data obtained on muscle area, total number, size, proportion and distribution of type 1 (slow-twitch) and type 2 (fast-twitch) fibers were analysed using multivariate regression. The results show that the ageing atrophy of this muscle begins around 25 years of age and thereafter accelerates. This is caused mainly by a loss of fibers, with no predominant effect on any fiber type, and to a lesser extent by a reduction in fiber size, mostly of type 2 fibers. The results also suggest the occurrence of several other age-related adaptive mechanisms which could influence fiber sizes and fiber number, as well as enzyme histochemical fiber characteristics.

Adolescent↗