Cystic fibrosis in teenagers and young adults.
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Adolescent↗
Biomedical subjects
S Conway
Publications and source records attributed to S Conway.
Needs assessment. All out of perspective.
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Data Collection↗
Role of insulin-like growth factor I in regulating growth hormone release and feedback in the male rat.
In vivo and in vitro (static incubation and perifusion) procedures were used to examine the role of insulin-like growth factors (IGFs) in growth hormone (GH) feedback. An alpha 2-adrenergic agonist, clonidine (CLON; 2 x 10(-8) M in vitro or 30 micrograms/ml/kg body weight i.v. in vivo), which mimics the hypothalamic mechanism triggering GH release, was injected to induce a GH surge. Feedback was initiated by human GH (hGH; 2 x 10(-6) M) in vitro or ovine GH (oGH) (20 micrograms/2 microliters intraventricularly) in vivo. GH-releasing factor (GRF; 1 x 10(-8) M) was added at the end of in vitro experiments to test pituitary responsiveness. The involvement of somatostatin (SRIF), GRF and IGFs in mediating GH feedback was evaluated in hypothalamic-pituitary coperifusion. CLON-induced GH release in this system was associated with increased GRF and decreased SRIF release, and the pattern was reversed by hGH. The influence of hGH was mimicked by IGF-I (1.5 x 10(-8) M), except that the GH release was depressed below baseline levels, suggesting a direct effect of IGF-I on the pituitary. Furthermore, the inhibitory effect of hGH on the CLON-induced GH surge and hypothalamic releasing factors (increased SRIF and decreased GRF) was reversed by antisera to IGF-I (1:100), IGF-II (1:100), or both. To determine whether IGF-I is released from hypothalamus or pituitary in response to GH, tissues were tested separately in static incubation. As compared with basal levels, incubation of hypothalami with hGH increased IGF-I and SRIF and decreased GRF release. Because GH and IGF-I release remained unchanged when pituitaries were incubated alone with hGH, the site of IGF-I release and GH feedback is most likely at the hypothalamic level. To evaluate the role of IGFs on GH feedback in vivo, male rats were prepared with permanently implanted 3rd-ventricular and jugular cannulae. CLON was administered intravenously, and oGH, IGF-I (0.5 microgram/2 microliters), and IGF-I and -II antisera (1:100) were injected intraventricularly. In this as in in vitro studies, IGF-I mimicked the inhibitory feedback effect of GH on the CLON-induced GH surge, and IGF antisera blocked GH feedback. We propose that these studies suggest that endogenous hypothalamic IGF-I mediates the influence of GH in the feedback mechanism by increasing SRIF and depressing GRF release.
Animals↗
The development of sexually dimorphic sensitivity to growth hormone (GH) feedback of the clonidine-induced GH surge in the rat.
This study investigates the development of sexually dimorphic sensitivity of the GH system to alpha 2-adrenergic stimulation and GH feedback in the rat. Sensitivity to alpha 2-adrenergic stimulation was tested with clonidine (CLN, an alpha 2-adrenergic agonist) which stimulates GH release in the adult male rat. Feedback was examined by testing whether human (h)GH suppressed the CLN-induced GH surge as previously demonstrated in adult male rats. The integrity of the pituitary and its capacity to respond to stimulation was tested at the end of the experiment by perifusing with GRF. Studies were conducted using a hypothalamic-pituitary coperifusion system which allows incubation of these tissues without the confounding influences of peripheral hormonal and extrahypothalamic neural factors. Tissue from prepubertal rats of 10, 20, 25 and 30 days of age, 50-day-old and adult rats (90-100 days) were evaluated. Results indicate that tissue from both male and female rats is sensitive to alpha 2-adrenergic stimulation at 10 days of age. In male tissue, there is an increase in GH release in response to CLN until 30 days of age, after which a slight decline in sensitivity occurs by 50 days of age and is maintained in adulthood. In regard to GH release from female tissue, a GH surge occurs in response to CLN until 30 days of age. At 50 days and in adulthood, this response is substantially diminished. Additionally, there is a profound sexual dimorphism in the capacity of hGH to suppress the CLN induced GH surge. In tissue from male rats, by 20 days of age there is an apparent GH-associated inhibition of the CLN-induced GH surge which is significant by 25 days, is more pronounced by 30 days of age, and is maintained after puberty at 50 days of age.(ABSTRACT TRUNCATED AT 250 WORDS)
Age Factors↗
Psychiatric morbidity in spouses of patients in rehabilitation after coronary-artery-bypass surgery.
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Adult↗
Effect of ethanol on insulin-like growth factor-II release from fetal organs.
This study examines the effect of ethanol (ETOH) exposure and nutrient restriction on the release of insulin-like growth factor (IGF)-II from 18- and 20-day explanted fetal organs. Fetuses were exposed to ETOH (E) in utero by feeding dams a 36% (calories derived from ETOH: 6.6% v/v) ETOH liquid diet. Control fetuses were offsprings of dams either pair-fed (P) a control liquid diet or ad libitum (A) fed a standard pelleted lab chow. Brain, heart, kidney, liver, lung, muscle, and placenta of fetuses from the same litter were pooled and explanted, and IGF-II concentration in explanted media was analyzed by radioimmunoassay. Maternal and fetal weights were determined during pregnancy and at sacrifice, respectively, to evaluate the influence of ETOH on growth. Both maternal and fetal weights were substantially reduced by ETOH on 18 and 20 days of gestation compared with both A and P controls. At 18 days of gestation, E fetuses (1.33 +/- 0.03 g) weighed less than either A (1.47 +/- 0.03 g) or P (1.54 +/- 0.04 g) fetuses. By 20 days, A mean fetal weight (4.19 +/- 0.23 g) was significantly greater than both P (3.74 +/- 0.06 g) and E (3.28 +/- 0.06 g) fetuses. IGF-II concentration in media from 18-day fetal explants was highest from E (brain, heart, liver, and placenta) and P tissues (kidney, lung, and muscle). IGF-II in media from A tissues (except placenta) was lower than both E and P levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Immunisation of the preterm baby.
The study was designed to quantify the preterm baby's response to routine childhood immunisations. A total of 69 preterm babies were put into two groups according to their gestational age: less than 32 weeks and between 32 and 35 weeks. Within each group the babies were randomly placed into one of three schedules for immunisation with diphtheria, tetanus, pertussis and oral poliomyelitis vaccines at 3, 4 and 5 months; 3, 4, 5 and 18 months; and 3, 4 and 10 months. Antibodies were measured before immunisation, one month after the third vaccine dose and at age 19 months. Of these children, 30 had further antibody estimations when they were between 4 and 5 years of age. One month after the third immunisation and at 19 months of age all infants, independent of gestational age, had adequate immunity to the four infections. Children sampled before and after their pre-school booster, with few exceptions, showed persistence of protective antibody and an enhanced response to the booster dose respectively. No correction needs to be made for prematurity when initiating routine immunisation in premature infants.
Age Factors↗
Effect of ethanol exposure on circulating levels of insulin-like growth factor I and II, and insulin-like growth factor binding proteins in fetal rats.
Maternal ethanol (ETOH) exposure is associated with impaired fetal growth. Because insulin-like growth factors (IGFs) are thought to be important in the regulation of fetal somatic growth, we examined the influence of maternal ETOH exposure on fetal growth and plasma levels of IGF-I, IGF-II, and IGF binding proteins (IGFBPs) in the rat model. Control (A) dams were fed a standard rat chow ad libitum. ETOH (E) consuming dams were fed a 36% ETOH diet, and pair-fed (P) dams were fed isocaloric amounts of a control liquid diet. All animals were killed on day 20 of gestation. Plasma concentrations of IGF-I and -II were determined by radioimmunoassay after formic acid-acetone extraction and heat inactivation of IGFBPs. Levels of IGFBPs in fetal plasma were estimated by Western ligand blotting after protein separation by SDS-PAGE and electrotransfer to nitrocellulose. Membranes were probed with [125I]IGF-I, and IGFBPs were identified by autoradiography, quantified by scanning densitometry and results expressed relative to corresponding IGFBPs in control fetal plasma. Maternal weight gain from conception to 20 days of pregnancy was reduced for E compared to P and A dams (p < 0.05 E vs. P or A). The same pattern was reflected in fetal weight that tended to be lower in P compared with A pups, and was significantly reduced in E pups compared with both groups (p < 0.0001 E vs. P or A). Thus, fetal growth was more retarded in E animals despite equal caloric and protein intake by E and P dams.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
A novel hypothalamic-dispersed pituitary co-perifusion model for the study of growth hormone secretion.
This study presents a novel, in vitro, hypothalamic-dispersed pituitary co-perifusion system (HPPS) developed to examine the influence of the hypothalamus on pituitary growth hormone (GH) secretion in a controlled environment. In this perifusion system, dispersed rat pituitary cells were loaded onto Biogel P-2 (P-2) beads in a 0.5-ml plexiglas chamber and were submerged in a 37 degrees C water bath. After stabilization, two hypothalami were placed into each chamber on a thin layer of P-2 beads and the chamber was re-equilibrated. To test the system, pituitary cells were stimulated either directly with growth hormone-releasing factor (GRF) or indirectly via the hypothalamus, with clonidine, an alpha 2-adrenergic (alpha 2) receptor agonist. Perifusion of HPPS or pituitary cells with GRF (40 ng/ml) induced a substantial endogenous GH surge. Clonidine (2 x 10(-8) M) treatment stimulated a GH surge in HPPS chambers, but not in chambers containing only pituitary cells. Thus, somatotrophs respond to hypothalamic factors released in response to clonidine and not directly to alpha 2 stimulation. To determine if the components involved in GH feedback are present in the perifusion system, HPPS chambers were sequentially perifused with hGH, clonidine, and GRF. hGH pretreatment suppressed the clonidine but not the GRF-induced GH surge(s) observed in chambers perifused with clonidine and GRF only. In chambers only containing pituitary cells, GH was only increased in response to GRF when sequentially perifused with all three substances. This study demonstrates the dynamic interaction between the hypothalamus and pituitary in the regulation of GH secretion in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
HIV-related risk behaviour in UK holiday-makers.
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Adolescent↗
The role of LH in the autofeedback inhibition of LH and FSH secretion in ovariectomized rats.
This study examined the role of exogenous LH in the autofeedback regulation of LH and FSH release in ovariectomized rats. The rats were implanted with third ventricular cannulae three weeks after ovariectomy and fitted with silastic jugular cannulae one week later. Baseline hormone levels were established on the day of experimentation in conscious, unrestrained animals. Thereafter, experimental animals received intraventricularly (IVT) either a 9 ug or 20 ug dose of a purified preparation of human (h)LH that did not crossreact in our rLH RIA. In response to 20 ug, but not 9 ug of LH, plasma levels of both LH and FSH were significantly reduced during the following one hour period compared to values in controls receiving buffer IVT. Administration of ovine (o)LH (6 ug, IVT), a preparation which crossreacts in the rLH RIA, significantly elevated plasma levels of detectable LH during the experimental period indicating that LH reaches the blood stream from the third ventricle and, thus, may effect endogenous hormone release at either the pituitary or hypothalamic levels. However, in animals preinjected with 9 or 20 ug of hLH IVT one hour earlier the surge of both LH and FSH in response to LHRH (25 ng iv) was not different from that in the buffer-injected controls receiving LHRH which indicates that pituitary responsiveness was not suppressed by the effective dose of hLH. The results of this study suggest that the inhibitory shortloop feedback of LH on endogenous LH and FSH secretion in ovariectomized rats occurs at the level of the hypothalamus.
Animals↗
Interaction between norepinephrine and serotonin in the neuroendocrine control of growth hormone release in the rat.
Both alpha 2-adrenergic (alpha 2) and serotonergic (5HT) neurons are associated with stimulation of GH secretion via GRH release. The object of this study was to determine whether the 5HT system is involved in the stimulation of GH secretion by alpha 2-receptor agonists. There are two parts of this study. In the first, the relationship between alpha 2-5HT systems were analyzed by determining if alpha 2-stimulated GH release is mediated by 5HT. In this model, systemically administered alpha 2-agonists [clonidine (CLON) or UK14,304] were tested against 5HT antagonists (meterogoline or cyproheptadine) or 5HT synthesis inhibitors (p-chlorophenylalanine methylester hydrochloride). In the second, sites of 5HT-GRH interaction were determined by testing the response to CLON after 5HT neurotoxin [5,7-dihydroxytryptamine (5,7-DHT)] microinjection at specific hypothalamic nuclei. In both experiments sequential blood samples were withdrawn from silastic jugular cannulas in unanesthetized, freely moving animals. Metergoline (0.045 and 0.135 mg/kg, iv) and cyproheptadine (0.969 micrograms/kg, iv) suppressed, in a dose-dependent manner, the CLON (33 or 66 micrograms/kg, iv)-induced GH surge that was detected 15-30 min after injection in control animals. Both cyproheptadine (0.969 micrograms/kg, iv) and p-chlorophenylalanine (300 mg/kg, ip) effectively suppressed the UK14,304 (220 micrograms/kg, iv)-induced GH surge that occurred 15-30 min after injection in control animals. These data suggest that an intact 5HT system is required for alpha 2-stimulated GH release. 5,7-DHT neurotoxin microinjected into the midline arcuate nucleus (6 micrograms/mg,iv) or bilaterally into the ventromedial nucleus or perifornical area (4 micrograms/0.2 microliter) 5 days previously suppressed the CLON (30 micrograms/kg)-induced GH surge only in animals with arcurate nucleus lesions. To determine if the suppression was mediated by inhibition of GH-releasing hormone (GRH) or stimulation of somatostatin (SRIF), an additional experiment was conducted including 5,7-DHT arcuate nucleus-lesioned animals injected with anti-SRIF. Inasmuch as anti-SRIF failed to reverse the 5,7-DHT suppression of GH secretion, the results of this experiment suggest that GRH mediates NE-5HT-induced GH secretion. In conclusion, these data suggest that alpha 2 activation of GH secretion requires intact serotonergic terminals in the arcuate nucleus and most likely involves GRH rather than SRIF, release.
5,7-Dihydroxytryptamine↗
Sexually dimorphic characteristics of clonidine-induced growth hormone release and autofeedback.
The mechanism underlying the sexually dimorphic pattern of GH secretion in the rat has not been clearly elucidated. In this study differences in the regulation of GH secretion in males and females were analyzed by examining their sensitivity to alpha 2-adrenergic (alpha 2) stimulation and GH autofeedback. The model used in testing this system was the capacity of ovine (o) GH, injected into the third ventricle, to suppress the endogenous GH surge induced by clonidine (CLON), an alpha 2-agonist. In morning experiments, CLON (30 micrograms/kg BW, iv) was injected between 1000-1100 h in males. oGH (20 micrograms in 2 microliters vehicle) injected 3 h earlier inhibited the GH surge, which peaked 15 min after CLON injection in control animals receiving CLON alone. In females there was both no change in plasma GH levels and no difference between treatment groups in animals receiving 30, 50, 100, or 150 micrograms/kg CLON and saline controls. Preinjection of 20 micrograms oGH in proestrous or diestrous animals or 30 micrograms oGH in diestrous animals 3 h before CLON treatment did not depress plasma GH levels below those found in animals receiving CLON alone. Further, neither reducing the preinjection time to 2 h nor injecting 7, 13, or 20 micrograms oGH at this preinjection period suppressed basal or CLON-induced GH release. To facilitate comparisons in subsequent experiments the male protocol was followed. In evening experiments, CLON (injected between 2210-2240 h) stimulated a significant GH surge in diestrous females. However, preinjected oGH lowered basal GH levels but failed to suppress the CLON-induced GH surge. In somatostatin (SRIF) antiserum (anti-SRIF; 0.5 ml, iv)-treated adult diestrous animals, CLON induced a significant GH surge that was suppressed by oGH preinjection. In normal sheep serum-treated animals there was no significant response to either CLON alone or in combination with oGH. To determine the influence of ovarian hormones on GH release females were ovariectomized (OVXed) either pre- or postpubertally. After adult OVX, CLON induced an increase in GH release that was not suppressed by oGH pretreatment. In prepubertally OVXed animals CLON induced a substantial GH surge that was suppressed in animals preinjected with oGH. In prepubertally OVXed animals implanted with testosterone capsules the response to CLON and oGH was not significantly different from that after prepubertal OVX alone. Sham-operated animals responded to treatment in a manner similar to unoperated cycling females.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
The prognostic value of DNA ploidy combined with histologic substaging for incidental carcinoma of the prostate gland.
Although current methods of histologic substaging for incidental prostatic carcinoma are useful, they offer only general indications of potential tumor behavior. To further define the biologic tendencies of stage A cancers, an examination was made of the role of DNA ploidy combined with histologic staging in archival material selected to achieve both a representative sample and long-term follow-up. With histology alone, 36% of stage A2 cancers and 9% of A1 neoplasms were progressive. Adding DNA flow cytometry to histology resulted in a significant improvement in the capacity of pathologic evaluation to predict outcome. Progression occurred in 67% of aneuploid stage A2 prostate cancers and in none of the nonaneuploid stage A1 tumors. Despite current limitations in the interpretation of DNA histograms from archival tissue, flow cytometry has significant potential in the pathologic evaluation of incidental prostatic carcinomas.
Aged↗
Retrospective DNA analysis of head and neck squamous cell carcinoma.
Abnormal cellular DNA content, a hallmark of malignancy, is known to occur in squamous cell carcinoma of the head and neck. The significance of this finding has yet to be elucidated. Paraffin-embedded blocks from 46 squamous cell carcinomas of the head and neck were sectioned, dewaxed, and made into a suspension of bare nuclei by mechanical mincing and enzymatic digestion. The nuclei were stained with propidium iodide, and quantitative DNA measurements were obtained with flow cytometry. The results were compared with existing prognostic factors: DNA aneuploidy was identified in 41% of the specimens and was significantly correlated with tumor size and surgical stage; the relationship between DNA aneuploidy and anatomic site approaches statistical significance. There was no correlation with histologic grade or presence or absence of cervical metastasis.
Aneuploidy↗
Opioid kappa receptors and the secretion of prolactin (PRL) and growth hormone (GH) in the rat. I. Effects of opioid kappa receptor agonists bremazocine and U-50,488 on secretion of PRL and GH: comparison with morphine.
The effects of bremazocine and U-50,488, two selective opioid kappa receptor agonists, and the preferential mu receptor agonist morphine on the secretion of PRL and GH were compared in conscious male rats bearing permanent right atrial cannulae for serial blood sampling and drug delivery. All three opioids stimulated PRL secretion in a dose-related manner, but the kappa agonists differed from morphine in several respects. They were considerably more potent than morphine in triggering a PRL response, but were unable to elevate PRL levels to more than 100 ng/ml, whereas morphine, at the highest dose (4.5 mg/kg), induced an almost twice larger response. Also their PRL-releasing effect was inhibited more strongly by the preferential kappa receptor antagonist Mr-2266 than by naloxone, whereas Mr-2266 and naloxone, which are equipotent as antagonists of the mu receptors, were equipotent in suppressing the PRL-stimulating effect of morphine, a mu agonist. In a complete contrast to morphine, which effectively stimulated GH secretion, the kappa agonists had no effect on GH release at lower doses and suppressed it at higher doses. It is concluded that the PRL-releasing effect of the kappa agonists is mediated by the kappa receptors which may participate with the mu receptors in regulation of PRL secretion by opioids. The GH-inhibiting effect of the kappa agonists requires further clarification.
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
Opioid kappa receptors and the secretion of prolactin (PRL) and growth hormone (GH) in the rat. II. GH and PRL release-inhibiting effects of the opioid kappa receptor agonists bremazocine and U-50,488.
An analysis of the GH release-inhibiting action of the opioid kappa receptor agonists bremazocine and U-50,488, established earlier, was attempted by testing the agonists against activation of GH secretion by morphine or clonidine in male rats bearing right atrial cannulae for serial blood sampling and drug delivery. Both kappa agonists inhibited the effect of subsequent administration of clonidine in a dose-related manner. Bremazocine was approximately ten times more potent than U-50,488, a ratio corresponding to the known affinities of the two compounds for the kappa receptors. The inhibiting action of bremazocine was more strongly reversed by the preferential kappa receptor antagonist Mr-2266 than by naloxone, neither of which interfered with the GH-stimulating effect of clonidine. Bremazocine, however, did not alter the activation of GH secretion by exogenous growth hormone releasing factor. Thus, the inhibiting effect of bremazocine and probably U-50,488 seems to be derived from stimulation of the kappa receptors which in turn activates a GH release inhibiting mechanism of unknown identify which, however, does not involve release of somatostatin. Both kappa agonists also inhibited the effect of morphine, but in this case U-50,488 was approximately hundred times less effective than bremazocine. Since bremazocine and U-50,488 are antagonists of the delta receptors, which seem to mediate the GH-releasing effect to morphine, their inhibiting effect in this instance may be related to this property rather than to an action on the kappa receptors. Bremazocine, but not U-50,488, was also highly effective in inhibiting stimulation of PRL secretion by morphine.(ABSTRACT TRUNCATED AT 250 WORDS)
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
On the mechanism of growth hormone autofeedback regulation: possible role of somatostatin and growth hormone-releasing factor.
To determine the role of somatostatin (SRIF) and GH-releasing factor (GRF) in GH autofeedback, 20 micrograms rat GH in 2 microliter were injected into the third ventricle (IVT) 1 or 3 h before injection of the alpha 2-receptor stimulator clonidine (50 micrograms/kg, iv), which elevates plasma GH and TSH levels in normal rats. GH preinjected 1 or 3 h before clonidine significantly suppressed the clonidine-induced GH surge, whereas TSH release was not affected by GH. Preinjection of ovine LH IVT following the same protocol did not inhibit the clonidine-induced GH surge, suggesting a specific effect of IVT GH. Passive immunization with 400 microliters sheep antisomatostatin serum did not reverse the inhibition of the clonidine-induced GH surge by exogenous GH administered IVT either 1 or 3 h before clonidine. The TSH response was augmented by this procedure. Furthermore, IVT GH did not reduce the surges of GH and TSH elicited by GRF (250 ng/kg, iv) and TRH (150 ng/kg, iv) administered 1 or 3 h after IVT rat GH. These results suggest that GH autofeedback is mediated by reduced GRF secretion, rather than enhanced SRIF release.
Animals↗