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Biomedical subjects

S J Kelly

Publications and source records attributed to S J Kelly.

At least 55 records · Page 3Linked to original sources
PubMed1989

Changes in the muscarinic cholinergic receptors in the hippocampus of rats exposed to ethyl alcohol during the brain growth spurt.

Rats were exposed to ethanol from postnatal day 4 to day 10, using an artificial rearing procedure. One group received ethanol administered by a cyclic regimen, which resulted in high peak blood ethanol concentrations (BACs). Another group received the same daily dose of ethanol using a regimen which resulted in stable, moderate BACs. Two control groups consisted of rats reared artificially but not exposed to alcohol and rats reared normally by dams. All rats were raised to adulthood. Approximately half the rats were tested for behavioral activity levels and then sacrificed in order to assay the hippocampus for levels of cyclic GMP and protein after incubation with bethanechol (a muscarinic cholinergic agonist). The remaining rats were sacrificed and their hippocampi were assayed for muscarinic cholinergic receptors and protein content. Exposure to cyclic BACs with high peaks but not exposure to stable moderate BACs resulted in greater behavioral activity levels in both sexes and also a greater cyclic GMP responsiveness to a muscarinic cholinergic agonist. Furthermore, exposure to cyclic BACs with high peaks resulted in a significantly larger dissociation constant and a greater number of muscarinic cholinergic receptors. There were no differences among groups or sexes in protein content of the hippocampus. There were no interactions of the alcohol treatment with sex. Thus, in adult rats, exposure to alcohol during the brain growth spurt results in an increase in the dissociation constant and number of muscarinic cholinergic receptors in the hippocampus.

Animals↗
PubMed1988

Impaired spatial navigation in adult female but not adult male rats exposed to alcohol during the brain growth spurt.

Two groups of male and female rats were given the same dose of alcohol using an artificial rearing procedure on postnatal days 4-10. One group received the alcohol in a condensed manner each day which caused cyclic blood alcohol concentrations (BACs) with high peaks. A second group received the alcohol in a uniform manner over each day which resulted in moderate, stable BACs. Two control groups consisted of male and female rats artificially reared but not exposed to alcohol and rats reared normally by dams. All rats were raised to 90 days of age and then tested for spatial navigation ability in the Morris water maze, which involved locating a hidden underwater platform using distal extramaze cues. Neither the alcohol treatments nor the artificial rearing had any effects on performance of adult male rats relative to suckle controls in this task. In contrast, the condensed alcohol exposure but not the uniform alcohol exposure resulted in detrimental performance in the Morris water maze by adult female rats. When the ability to locate and escape onto a visible platform was examined, there were no differences between the female groups given condensed alcohol exposure or artificially reared on milk solution alone. Thus, exposure to high BACs during the brain growth spurt has a lasting and selective detrimental effect on spatial navigation learning in adult female but not adult male rats.

Animals↗
PubMed1988

Percutaneous needle aspiration biopsy of chest lesions. New instrument and new technique.

From March 1986 to April 1987, 70 percutaneous needle aspiration (PCNA) procedures were performed in 66 consecutive patients. Seven immunocompromised patients had the procedure performed to obtain culture material from the lung, and 59 patients with chest lesions were analyzed. This includes 49 patients with either a lung nodule or mass. In the remaining ten patients, there were three chest wall or pleural lesions, two aortic pulmonary window lesions, two right hilar lesions, and three anterior mediastinal lesions. Forty of these 59 patients were ultimately proven to have a malignancy. The diagnostic yield for malignant disease by cytology and histology of PCNA was 97.5 percent (39 of 40). Twelve patients had a final diagnosis of benign disease. The diagnostic yield in benign diseases by PCNA was 91.6 percent (11 of 12). The remaining seven patients do not yet have a final diagnosis, though the clinical course favors benign disease in six of these patients. We attribute the major reason for this high specific diagnostic yield in both malignant and benign diseases to the ability of obtaining histologic specimens for interpretation.

Biopsy, Needle↗
PubMed1987

Role of peripheral and central opioid activity in analgesia induced by restraint stress.

Rats subjected to prolonged restraint showed an increase in tail flick latency which outlasted the period of restraint by 15 min. This restraint could be blocked but not reversed by 1 mg/kg of naltrexone hydrochloride given subcutaneously. Naltrexone methobromide, administered subcutaneously in doses of 10 or 25 mg/kg, did not block the analgesia indicating that peripheral opioid receptors were probably not involved. Naltrexone hydrochloride was shown to have no effect on brain tryptophan uptake in restrained rats, a neurochemical event which had previously been shown to be critical to restraint-induced analgesia.

Analgesia↗
PubMed1987

Microencephaly and hyperactivity in adult rats can be induced by neonatal exposure to high blood alcohol concentrations.

To investigate whether or not blood alcohol concentration during the brain growth spurt has an influence on the permanency of alcohol-induced central nervous system damage, an artificial rearing technique was used to administer a daily dose of alcohol (6.6 g/kg/day) to neonatal rats during postnatal days 4 to 10. The alcohol was administered either in a condensed pattern over 8 h resulting in cyclic blood alcohol concentrations with high peaks, or uniformly over each 24-h period resulting in stable, but low peaks. The condensed alcohol exposure resulted in considerable microencephaly (20% to 25%), with significant growth deficits in the cerebrum, cerebellum, and brain stem of rats of either sex at day 10; there still was significant microencephaly (16% to 19%) in adult rats that received the condensed alcohol exposure as neonates. Furthermore, activity at day 90 in rats of either sex that had condensed alcohol exposure was elevated compared with that of the gastrostomy control group. In contrast, the rats having uniform alcohol exposure had only nonsignificant changes in brain weight both on day 10 and day 90 and did not exhibit hyperactivity at day 90. Thus, neonatal alcohol exposure producing high blood alcohol concentrations caused permanent deficits in brain growth and significant changes in activity, whereas the same daily dose of alcohol administered in a pattern that resulted in consistently low blood alcohol concentrations failed to produce either permanent microencephaly or increased activity. These data support the hypothesis that patterns of alcohol exposure that produce high concentrations in the blood, such as "binge-drinking," increase the risk of permanent damage to the developing brain.

Animals↗
PubMed1987

Transbronchial needle aspiration.

To determine the value of transbronchial needle aspiration biopsy in the diagnosis of sarcoidosis, we reviewed a one-year experience of consecutive patients with sarcoidosis presenting with hilar and/or paratracheal adenopathy. The sensitivity of transbronchial needle aspiration biopsy in obtaining noncaseating granulomas was 90%. This yield exceeds that of most published reports of transbronchial lung biopsy and bronchial mucosal biopsy and suggests that transbronchial needle aspiration biopsy may be a valuable diagnostic tool in the evaluation of these forms of sarcoidosis.

Biopsy, Needle↗
PubMed1987

Developmental changes in alcohol pharmacokinetics in rats.

Developmental changes in the pharmacokinetics of alcohol could influence the outcome of alcohol exposure during different periods of postnatal development. Hence, the development of the ability to absorb and metabolize alcohol in the rat was examined by administering an acute dose (2.5 g/kg) of ethanol in milk formula by intragastric intubation to rats of 1, 2, 4, 6, 8, 10, 15, 21, 30, and 60 days of age. Each animal in a particular litter was assigned a different time point following intubation when its blood alcohol concentration (BAC) was determined from a tail blood sample. At all ages tested, maximum BACs occurred between 1.25 and 1.5 hr following intubation. However, maximum BACs decreased with age from 155 mg/dl in 1-day-old rats to 111 mg/dl in 60-day-old rats. Furthermore, the rate of alcohol clearance was slower in the younger rats. By linear regression analysis, the elimination rate of alcohol in 1-day-old rats was estimated to be 7.5 mg/dl/hr which increased to 42.2 mg/dl/hr in 60-day-old-rats. By 8 hr following intubation, rats that were 21 days of age and older had completely cleared the alcohol, whereas the younger rats (1-15 days of age) had not. No consistent sex differences were seen in either the maximum BAC or clearance rate. Since developmental changes in the ability to clear alcohol occur throughout the first 60 postnatal days in the rat, controlling for these changes is essential when looking for critical periods of an organ's vulnerability to damage by alcohol.

Aging↗
PubMed1987

Severity of alcohol-induced deficits in rats during the third trimester equivalent is determined by the pattern of exposure.

The pattern of alcohol exposure has been suggested to be an important determinant of fetal alcohol effects. Rats were exposed to alcohol and reared artificially on postnatal days (PD) 4-10. A uniform alcohol exposure group received alcohol (6.6 g/kg/day) in 12 daily feedings (every 2 hrs) resulting in stable BACs below 100 mg/dl. A condensed alcohol exposure group also received 6.6 g/kg/day but the alcohol was concentrated in 4 of 12 daily feedings giving peak BACs above 400 mg/dl. Condensed alcohol exposure induced a large degree of microencephaly on PD 10 which was still present on PD 90. Uniform exposure caused a mild degree of microencephaly on PD 10 which could not be detected at PD 90. Correlated with these brain changes were changes in behavior during development. Condensed exposure to alcohol increased locomotion during postnatal days 14 to 20. Condensed alcohol exposure caused delays in the development of balancing ability and coordinated hindlimb movements. Thus, the pattern of alcohol exposure appears more critical than the dose in determining the degree of damage inflicted by alcohol to the developing central nervous system.

Animals↗
PubMed1986

Sympathetic control of tryptophan uptake and morphine analgesia in stressed rats.

Guanethidine treatment decreased morphine analgesia exhibited by restrained rats but had no effect on morphine analgesia exhibited by unrestrained rats or on baseline pain sensitivity. Guanethidine also prevented the rise in tryptophan uptake into the brain induced by the restraint stress. It is argued that the prevention of the stress-induced increase in brain tryptophan uptake is causal to guanethidine's attenuation of morphine analgesia exhibited by restrained rats, since the increase in brain tryptophan uptake has already been shown to be critical to this phenomenon. The blockade of the stress-induced increase in brain tryptophan uptake and morphine analgesia by guanethidine support the hypothesis that these effects depend upon sympathetic activity.

Analgesia↗
PubMed1986

In vitro growth of sheep erythroid progenitors.

We have attempted to define culture conditions suitable to support the in vitro growth of early erythroid progenitors (BFU-E), derived from the liver or bone marrow and blood of fetal and adult sheep. Testing a wide variety of conditions showed that only some batches of fetal lamb sera made a notable difference to growth. BFU-E from normal fetal blood were demonstrated sporadically: they appeared regularly in low numbers in blood taken during erythroid (anaemic) stress. Adult blood only contained sporadic BFU-E during severe anaemic stress. This difficulty in demonstrating circulating BFU-E in sheep may be due to a genuine paucity of such cells or to an undefined requirement for in vitro growth.

Animals↗
PubMed1986

Loss of luteinizing hormone bioactivity in patients with prostatic cancer treated with an LHRH agonist and a pure antiandrogen.

Chronic treatment of adult men with LHRH agonists causes a decrease in serum testosterone and 5 alpha-dihydrotestosterone to castrate levels. In the presence of such low levels of circulating testicular androgens, the concentration of serum LH measured by radioimmunoassay (RIA) sometimes remains normal or is only partially inhibited. In order to assess the biological activity of circulating LH, we have used the mouse interstitial cell assay. Blood samples were obtained from patients with prostatic carcinoma treated with the LHRH agonist [D-Trp6] LHRH ethylamide in combination with the pure antiandrogen Flutamide (Euflex). While serum LH levels measured by RIA were only partially reduced from 2.2 +/- 0.3 (SEM) to 1.1 +/- 0.1 ng/ml after 3 months of therapy, bioactive LH was markedly inhibited from 0.43 +/- 0.04 to 0.030 +/- 0.007 ng/ml, thus causing the ratio of biologically active to radioimmunoassayable LH to drop from 0.26 +/- 0.03 to 0.03 +/- 0.01. In the same patients, serum testosterone levels were decreased from 3.91 +/- 0.51 to 0.14 +/- 0.05 ng/ml after 3 months of treatment. In patients treated for 6 months, the bio/immuno ratio was still reduced at 0.032 +/- 0.005. These data show a marked loss of LH biological activity during treatment of adult men with an LHRH agonist and an antiandrogen. The close parallelism observed between serum testosterone and bioactive LH levels suggests that the loss of biological activity of the gonadotrophin is mainly, if not exclusively, responsible for the inhibition of testicular androgen secretion observed during chronic treatment with LHRH agonists.

Adenocarcinoma↗
PubMed1985

An increase in tryptophan in brain may be a general mechanism for the effect of stress on sensitivity to pain.

The role of the stress-induced increase in the uptake of tryptophan in brain in opioid-induced analgesia was investigated by modifying the uptake of amino acid in brain with injections of competing amino acids. Blockade of analgesia by valine (200 mg/kg, i.p.) alone, and by valine and tyrosine (100 mg/kg, i.p.), but not by valine and tryptophan (100 mg/kg, i.p.), was taken to indicate that an increase in the uptake of tryptophan in brain was involved in opioid-induced analgesia. Morphine-induced analgesia exhibited by rats that were habituated to the laboratory and not restrained did not involve an increase in the uptake of tryptophan in brain. However, a mild form of restraint, or exposure to a novel environment interacted with morphine to induce analgesia which involved an increase in the uptake of tryptophan in brain. These stressors did not affect sensitivity to pain in the absence of morphine. Analgesia induced by 3 hr of restraint, which was preventable by naltrexone (1 mg/kg, s.c.) but not reversible by naloxone (1 mg/kg, s.c.), also involved an increase in the uptake of tryptophan in brain. It is concluded that the endogenous opioid-induced analgesia that is induced by stress alone and analgesia induced by stress interacting with morphine, both depend on an increase in the uptake of tryptophan into the brain.

Animals↗
PubMed1984

Electrolytic raphe magnus lesions block analgesia induced by a stress-morphine interaction but not analgesia induced by morphine alone.

Morphine analgesia in the tail withdrawal test was examined in rats which had had lesions of the nucleus raphe magnus (NRM) or sham operations. Half of the rats were tested while restrained, whereas the other half were not restrained. In the sham-operated rats, restraint potentiated the analgesic response to morphine. Lesions of the NRM had no effect on unrestrained rats but reduced the morphine analgesia exhibited by restrained rats so that it was indistinguishable from that of unrestrained rats. The NRM seems to be involved in analgesia induced by an interaction of morphine and restraint but not in analgesia induced by morphine alone.

Animals↗
PubMed1984

Evidence that stress augments morphine analgesia by increasing brain tryptophan.

Morphine analgesia measured by the tail withdrawal test was examined in rats that were either restrained or left free during testing. It was found that restraint potentiated morphine analgesia and decreased the latency of the peak analgesic effect. Methysergide, a serotonin antagonist, and valine, which prevents the increase in brain tryptophan induced by restraint, blocked the effect of restraint on morphine analgesia. Valine did not alter analgesia in unrestrained rats. An increase in brain tryptophan uptake induced by stress is suggested as a possible mechanism by which stress can interact with pain modulation systems.

Analgesia↗