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Biomedical subjects

J Hotchkiss

Publications and source records attributed to J Hotchkiss.

At least 19 recordsLinked to original sources
PubMed1995

Concurrent increases in the storage and release of mucin-like molecules by rat airway epithelial cells in response to bacterial endotoxin.

Mucus hypersecretion is a prominent response of the airways to bacterial infections. Recent findings showed that bacterial endotoxin, a lipopolysaccharide complex released from the bacterial cell wall, was able to induce at least one component of the hypersecretory response, i.e., an increase in the amount of stored epithelial mucosubstances (1, 2). The goal of the present study was to determine whether endotoxin also was capable of increasing mucosubstance release from cells. Based on evidence that human mucin antibodies A10G5 and B6E8 cross-reacted with rat mucin-like molecules, we used the antibodies in enzyme-linked immunosorbent assays (ELISA) to compare mucin concentrations in bronchoalveolar lavage (BAL) fluid from endotoxin-treated and control rats. Results showed that endotoxin treatment increased the amount of released mucin over that in controls 1.5-fold at 96 h and 2.5-fold at 168 h after instillation. Thus, these studies have defined the previously detected mucosubstances as mucin-like molecules and showed that endotoxin increases their release from, as well as their storage in, rat airway epithelium. Concurrent increases in storage and release suggest that endotoxin also stimulates mucin synthesis and/or stability.

Animals↗
PubMed1993

Tuberculosis and poverty.

OBJECTIVE: To examine whether the historical link between tuberculosis and poverty still exists. DESIGN: Retrospective study examining the notifications of all forms of tuberculosis by council ward over a six year period and correlating this with four indices of poverty; council housing, free school meals, the Townsend overall deprivation index, and the Jarman index. SETTING: The 33 electoral wards of the city of Liverpool. SUBJECTS: 344 residents of Liverpool with tuberculosis. RESULTS: The rate of tuberculosis was correlated with all measures of poverty, the strongest correlation being with the Jarman index (r = 0.73, p < 0.0001). This link was independent of the high rates of tuberculosis seen in ethnic minorities. CONCLUSION: Tuberculosis remains strongly associated with poverty.

Adolescent↗
PubMed1993

Effects of naloxone on estrogen-induced changes in hypothalamic gonadotropin-releasing hormone pulse generator activity in the rhesus monkey.

In the ovariectomized rhesus monkey, estradiol (E2) markedly reduces the frequency of the GnRH pulse generator as monitored by LH pulse frequency and the concurrent changes in hypothalamic electrical activity, an action mimicked by morphine. In addition, the duration of the increments in multiunit electrical activity (MUA volleys) that precede each LH pulse is decreased by estrogen administration, an action also shared by morphine. The role of endogenous opioids in these actions of E2 was investigated in 8 ovariectomized animals restrained in primate chairs. They were fitted with indwelling cardiac catheters and with bilateral arrays of recording electrodes chronically implanted in the mediobasal hypothalamus. Physiological serum E2 levels achieved by subcutaneous implantation of E2-containing Silastic capsules increased MUA volley interval from 50.8 +/- (SEM) 1.6 min in the control period to 81.1 +/- 6.2 min following E2. Mean MUA volley duration decreased from 21.9 +/- 1.0 to 13.0 +/- 0.7 min. The placement of empty Silastic capsules had no effect on MUA volley duration or interval. Naloxone administration (2.5 mg bolus followed by a 1 mg/h infusion lasting 4-8 h) completely (n = 4) or partially (n = 2) blocked the effects of E2 on MUA volley interval in 6 of the 8 monkeys, and was without effect in the remainder. In contrast, however, naloxone had little or no effect on the action of E2 on MUA volley duration, (13.0 +/- 0.7 vs. 14.0 +/- 0.9 min). These findings suggest that the inhibitory action of E2 on GnRH pulse generator frequency, like that of all other gonadal steroids studied to date, may be mediated by endogenous opioids.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Ovarian control of gonadotropin hormone-releasing hormone pulse generator activity in the rhesus monkey: duration of the associated hypothalamic signal.

The activity of the GnRH pulse generator in the rhesus monkey is associated with abrupt increases in multiunit electrical activity (MUA) volleys recorded from the mediobasal hypothalamus that precede each pulse of LH in the peripheral circulation. In long-term ovariectomized animals the duration of these MUA volleys is 10-25 min and consists of a brief initial 'overshoot' followed by a plateau phase that ends in a rapid decline to baseline activity. In intact monkeys, however, the MUA volley lasts only 1-3 min, a duration equivalent to the overshoot in ovariectomized animals. In addition, the maximal frequency of neuronal activity during each MUA volley is reduced in normal animals when compared to castrates. As shown in earlier studies, estradiol given to ovariectomized monkeys causes a reduction in the duration of MUA volleys to that characteristic of intact animals within 3-5 h. In contrast to this acute effect of estradiol, the increase in MUA volley duration following ovariectomy is a gradual phenomenon, 4-6 weeks being required to achieve the MUA volley duration observed in long-term ovariectomized monkeys. A similar slow time course was observed for the increase in maximal neuronal frequency during each MUA volley. This protracted effect of ovariectomy on MUA volley duration and firing rate may be the consequence of hypothalamic remodelling but this consideration must be tempered by the observation that estradiol reverses these phenomena within hours.

Animals↗
PubMed1993

Ambient light modifies gonadotropin-releasing hormone pulse generator frequency in the rhesus monkey.

In the course of previous studies using continuous monitoring of the electrophysiological correlates of GnRH pulse generator activity, characterized by episodic increases in hypothalamic multiunit electrical activity (MUA volley), it was noticed that the nocturnal slowing of pulse generator frequency was an acute phenomenon observable in the first MUA volleys after the lights were turned off, as was the increase in frequency when the lights were turned on in the morning. This suggested that the reduction in pulse generator frequency at night may not be the consequence of an intrinsic diurnal rhythm, but an effect of light per se. Indeed, as reported herein, such an effect was observed when the lights were turned on or off at times other than the normal illumination period (normal light schedule, lights on from 0700-1900 h). That this was not simply a response to arousal was shown by awakening the animals with loud recorded noises in total darkness at the same unaccustomed times without a resulting change in frequency. This suggests that the effect of light is specific, perhaps mediated by the retino-hypothalamic tract. This direct action of light, however, is superimposed upon a diurnal rhythm, as shown by a reduction in pulse generator frequency during the subjective night when the monkeys were kept in constant light or constant darkness.

Animals↗
PubMed1992

Hypoglycemic 'stress' and gonadotropin-releasing hormone pulse generator activity in the rhesus monkey: role of the ovary.

Observations of long standing have suggested that the 'stress' of chair restraint inhibits the GnRH pulse generator in normal female monkeys while this phenomenon is rarely observed in ovariectomized animals. The role of the ovary in the response of the GnRH pulse generator to the stress of insulin hypoglycemia was investigated in both intact and ovariectomized rhesus monkeys. Following an overnight fast the animals, previously habituated to restraint, were placed in primate chairs and GnRH pulse generator activity monitored electrophysiologically. Insulin-induced reductions in mean blood glucose concentrations of 10-40% of control values interrupted pulse generator activity in intact monkeys but were without effect in ovariectomized animals. With larger reductions in blood glucose, pulse generator activity was interrupted in both groups but the inhibition was twice as long in intact than in ovariectomized animals. The reduced responsiveness of ovariectomized animals to insulin hypoglycemia was significantly reversed by estradiol replacement. Naloxone administration did not prevent the hypoglycemia-induced inhibition of pulse generator activity in either intact or ovariectomized rhesus monkeys. It is concluded that hypoglycemic 'stress' inhibits the GnRH pulse generator by a nonopioidergic mechanism and that ovarian products, most probably estradiol, exacerbate this effect.

Animals↗
PubMed1991

Radiotelemetric monitoring of hypothalamic gonadotropin-releasing hormone pulse generator activity throughout the menstrual cycle of the rhesus monkey.

Continuous monitoring of the electrophysiological manifestations of GnRH pulse generator activity was achieved by radiotelemetry throughout the menstrual cycles of unrestrained rhesus monkeys. The characteristic increases in hypothalamic multiunit activity (MUA volleys) associated with each LH pulse measured in the peripheral circulation were of lower frequency during the luteal phase than in the follicular phase of the cycle. Multiunit activity volley frequency increased as functional luteolysis progressed and achieved maxima of approximately one volley per hour within the first few days of the follicular phase. Unexpectedly, a dramatic decline in pulse generator frequency was observed coincidentally with the initiation of the preovulatory LH surge. Evidence is presented to support the conclusion that this deceleration of pulse generator activity is the consequence of the preovulatory rise in plasma estrogen concentration. As reported in women, a significant reduction in GnRH pulse generator frequency was observed at night during the follicular phase, but not during the luteal phase, of the menstrual cycle.

Animals↗
PubMed1990

Duration of phasic electrical activity of the hypothalamic gonadotropin-releasing hormone pulse generator and dynamics of luteinizing hormone pulses in the rhesus monkey.

The secretion of luteinizing hormone (LH) by the pituitary gland is a pulsatile phenomenon. In the rhesus monkey, each pulse of LH in the peripheral circulation is associated with a characteristic increase in multiunit electrical activity (MUA) recorded from the medial basal hypothalamus. These "volleys" of electrical activity initiate the release of gonadotropin-releasing hormone (GnRH) into the pituitary portal circulation from the terminals of neurosecretory cells. Their duration varies from 1-3 min in normal, adult intact females to 10-25 min in long-term ovariectomized monkeys. A variety of pharmacological interventions also modify volley duration. The purpose of this investigation was to determine the physiological significance of alterations in volley duration. The dynamics of LH pulses in ovariectomized animals were observed in a number of experimental circumstances in which MUA volley duration was reduced from a maximum of 23 min to a minimum of 4 min without significantly altering their frequency. The magnitude of each LH pulse was assessed by calculating the area under the curve delineated by the time course of LH above baseline. In eight experiments, a linear regression of these values on volley duration failed to reveal a significant correlation between MUA volley duration and the magnitude of LH pulses. These results suggest that all of the GnRH secreted per pulse is released at the onset of each MUA volley, the remainder of the increase in electrical activity having no further action on GnRH secretion, although effects on other systems cannot be excluded.

Activity Cycles↗
PubMed1990

Corticotropin-releasing factor and gonadotropin-releasing hormone pulse generator activity in the rhesus monkey. Electrophysiological studies.

The effect of corticotropin-releasing factor (CRF) on the hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator, the central neuronal system governing pulsatile pituitary luteinizing hormone (LH) secretion, was studied electro-physiologically in 6 ovariectomized rhesus monkeys bearing bilateral arrays of recording electrodes implanted in the mediobasal hypothalamus. 'Volleys' of increased multiunit activity (MUA) were recorded for 6-10 h in animals placed in primate chairs. The circulating concentrations of LH and cortisol were determined by radioimmunoassay in blood samples taken every 10 min for 3-4 h prior to the administration of CRF (200 micrograms, i.v.) and for 3-6 h thereafter. CRF resulted in a significant decrease in the frequency of pulse generator activity in 4 of 6 animals, a significant decrease in the duration of MUA volleys and a rise in circulating cortisol levels in all 6 monkeys. Treatment with metyrapone (30 mg/kg, i.m.), an inhibitor of adrenal steroidogenesis that prevented the CRF-induced rise in serum cortisol levels, did not reverse the inhibitory effects of CRF on the frequency or duration of MUA volleys. The opiate antagonist naloxone (0.8 mg/kg, i.v., 10 min prior to CRF followed by 0.8 mg/kg/h infusion) blocked the effects of CRF on MUA volley frequency in 2 of 3 animals, but failed to block the effect of CRF on MUA volley duration, suggesting that endogenous opioids may mediate the action of CRF on pulse generator frequency but not on duration.

Animals↗
PubMed1990

Duration and frequency of multiunit electrical activity associated with the hypothalamic gonadotropin releasing hormone pulse generator in the rhesus monkey: differential effects of morphine.

The effects of morphine on the frequency and duration of the characteristic bursts or 'volleys' of multiunit electrical activity (MUA) associated with pulsatile pituitary luteinizing hormone (LH) secretion were studied in unanesthetized ovariectomized rhesus monkeys bearing bilateral arrays of electrodes implanted in the mediobasal hypothalamus. Morphine administration resulted in a dose-dependent decrease in MUA volley duration and frequency. When morphine was infused at 10 micrograms/kg/h, the inhibiting effect on volley duration was observed without a change in volley frequency. It is concluded that the frequency and duration of hypothalamic MUA volleys associated with pulsatile LH secretion may be independently regulated.

Animals↗
PubMed1987

Unexpected responses of the hypothalamic gonadotropin-releasing hormone "pulse generator" to physiological estradiol inputs in the absence of the ovary.

In the rhesus monkey (Macaca mulatta), the frequency of pulsatile gonadotropic hormone release is relatively constant in the face of widely varying levels of estradiol (E2) in the peripheral circulation--e.g., in the course of the follicular phase of the menstrual cycle and after ovariectomy. This suggests that modulation of the hypothalamic gonadotropin-releasing hormone (GnRH) "pulse generator" by this steroid is not of major physiological importance. Herein is described the unexpected inhibition or total blockade of the electrical activity of this pulse generator in ovariectomized monkeys by physiological levels of exogenous E2. This inhibition began 2-4.5 hr after the initiation of E2 infusion and was noted 1 to 3 weeks after subcutaneous implantation of E2-containing capsules. Pulse generator activity was also arrested during the initiation and subsequent development of estrogen-induced surges of luteinizing hormone. We propose that this inhibition of hypothalamic GnRH pulse generator activity by E2 in ovariectomized monkeys reflects the absence of an ovarian factor that normally protects this neuronal system from the inhibitory action of estrogen during the menstrual cycle.

Action Potentials↗
PubMed1985

Changes in sex hormone-binding globulin binding capacity and percent free estradiol during development in the female rhesus monkey (Macaca mulatta): relation to the metabolic clearance rate of estradiol.

Circulating sex hormone-binding globulin (SHBG) binding capacity and percent free estradiol (% free E2) were measured in separate groups of female rhesus monkeys from 2 months of age through adulthood (greater than 4.5 yr old). The SHBG concentration alone was also measured in 11 adult and 6 sexually immature animals on the same day as the blood MCR of E2. Serum SHBG levels were the highest (range, 12-25 micrograms T/dl) and the % free E2 the lowest (0.88%) in animals 6 months old or less. After the age, serum SHBG binding capacity declined generally at an average rate of 0.11 SHBG U (microgram T/dl)/month toward a nadir in adulthood. There was no difference in the SHBG levels in the follicular or luteal phase of the menstrual cycle. The relative blood MCR E2 and circulating SHBG binding capacity were significantly greater (P less than 0.001) in the sexually immature animals [MCR E2, 48.4 +/- 5.2 (SEM) liters/day . kg body wt; SHBG, 9.8 +/- 1.0 microgram T/dl, n = 6] than in adult animals (MCR E2, 27.7 +/- 1.7 liters/day kg body wt; SHBG, 4.6 +/- 0.3 microgram T/dl, n = 11). There was no relation between the MCR E2 and circulating SHBG levels within each group of adult or immature animals. The mean % free E2 doubled (to 1.6%) between 1 and 54 months of age; there was no relation between total circulating E2 and % free E2. Although a high SHBG binding capacity and a low % free E2 in the circulation of the immature animal does not inhibit the metabolic clearance of E2; it remains possible that these factors (and others) may hinder the access of E2 to reproductive target tissues and thereby contribute to the slow acquisition of reproductive competence in this species.

Aging↗
PubMed1983

The metabolic clearance rate and the production rate of estradiol in sexually immature and adult female rhesus monkeys.

The blood MCR of estradiol (MCRE2) was measured in 34 experiments with 10 adult (4.7-8.2 kg) and 13 prepubertal (1.8-3.0 kg; 13-23 months old) female rhesus monkeys using the constant infusion technique. Twenty-six of the studies were performed using an adult and an immature animal simultaneously. Twenty-four of the studies were performed in pentobarbital-anesthetized animals, while the remainder used conscious animals restrained in primate chairs. The blood MCRE2 in the adult female was 167.5 +/- 9.5 liters/day (mean +/- SE; n = 14) or 27.5 +/- 1.4 liters/day x kg BW, and was not altered by anesthesia, stage of the menstrual cycle, amenorrhea of more than 60 days duration, or the site of origin of the blood used to calculate the MCR (radial artery, femoral artery, femoral vein, or saphenous vein). While the absolute MCRE2 in the immature animal (either anesthetized or conscious) was less than that in the adult, when corrected for body weight, the relative MCRE2 (in liters per day/kg BW) of the conscious immature animal was double that seen in the adult [48.4 +/- 5.2 (n = 6) vs. 27.5 +/- 1.4 (n = 1.4)]. Anesthesia caused a profound depression of the MCRE2 in the immature animal, which could be prevented if the body temperature of the animal was maintained at 37 C during the prolonged period of anesthesia. The production rate of estradiol (PRE2) was calculated as the product of the serum estradiol concentration (in micrograms per liter; measured by RIA techniques) and the plasma MCRE2 (blood MCRE2 x 1 - hematocrit). In the adult animals, the PRE2 ranged from 1.9 - 35.5 micrograms/day, and was lowest in the amenorrheic animals and highest during the late follicular phase. The PRE2 in the immature animals ranged from unmeasurable to 1.7 micrograms/day, averaging 0.7 +/- 0.2 micrograms/day (n = 12) in those animals where it could be measured. These data support the hypothesis that the low circulating estradiol levels in the immature animal are the consequence of a low PRE2 coupled with a high MCRE2.

Anesthesia↗