PubMed Health⌕ Search

Biomedical subjects

J A Finkelstein

Publications and source records attributed to J A Finkelstein.

At least 73 records · Page 4Linked to original sources
PubMed1990

Developmental changes in levels of growth hormone mRNA in Zucker rats.

Levels of pituitary growth hormone (GH) messenger RNA (mRNA) were compared in groups of genetically obese (fa/fa) and lean (Fa/-) littermate male Zucker rats at four different ages, 3, 5, 9, and 11 weeks, in order to determine the earliest age at which a difference between the two groups could be detected. No difference was seen in three-week-old animals. Five weeks of age was the earliest time at which the level of GH mRNA was significantly decreased in the obese rats; this decrease was present at all subsequent ages. Mean serum growth hormone levels were lower in obese animals at all ages, but the differences were not statistically significant because of the large individual variation associated with the pulsatile nature of GH release. The earliest occurrence of differences in GH mRNA level is later than some of the obesity associated abnormalities present in adipose tissue. The earliest time of the GH mRNA differences can be associated with the time when decreased protein deposition is initially seen in the obese rats. Because of this association, decreased GH mRNA may enhance the development of obesity.

Aging↗
PubMed1990

Some benzyl-substituted imidazoles, triazoles, tetrazoles, pyridinethiones, and structural relatives as multisubstrate inhibitors of dopamine beta-hydroxylase. 4. Structure-activity relationships at the copper binding site.

Structure-activity relationships (SAR) were determined for novel multisubstrate inhibitors of dopamine beta-hydroxylase (DBH; EC 1.14.17.1) by examining the effects upon in vitro inhibitory potencies resulting from structural changes at the copper-binding region of inhibitor. Attempts were made to determine replacement groups for the thione sulfur atom of the prototypical inhibitor 1-(4-hydroxybenzyl)imidazole-2-thione described previously. The synthesis and evaluation of oxygen and nitrogen analogues of the soft thione group demonstrated the sulfur atom to be necessary for optimal activity. An additional series of imidazole-2-thione relatives was prepared in an effort to probe the relationship between the pKa of the ligand group and inhibitory potency. In vitro inhibitory potency was shown not to correlate with ligand pKa over a range of approximately 10 pKa units, and a rationale for this is advanced. Additional ligand modifications were prepared in order to explore bulk tolerance at the enzyme oxygen binding site and to determine the effects of substituting a six-membered ligand group for the five-membered imidazole-2-thione ligand.

Animals↗
PubMed1990

Effect of exercise and obesity on skeletal muscle amino acid uptake.

The genetically obese Zucker rat has a reduced capacity to deposit dietary protein in skeletal muscle. To determine whether amino acid uptake by muscle of obese Zucker rats is impaired, soleus strip (SOL) and epitrochlearis (EPI) muscles from 10-wk-old lean and obese Zucker rats were studied in vitro by use of [14C]alpha-aminoisobutyric acid (AIB). Muscles from fasted rats were incubated under basal conditions at rest or after a 1-h treadmill run at 8% grade. To equate total work completed, lean and obese rats ran at 27 and 20 m/min, respectively. Muscles were pinned at resting length, preincubated for 30 min at 37 degrees C in Krebs-Ringer bicarbonate buffer containing 5 mM glucose under 95% O2-5% CO2, and then incubated up to 3 h in Krebs-Ringer bicarbonate with 0.5 mM AIB, [14C]AIB, and [3H]inulin as a marker of extracellular fluid. Basal AIB uptake in EPI and SOL from obese rats was significantly reduced by 40 and 30% (P less than 0.01), respectively, compared with lean rats. For both lean and obese rats, exercise increased (P less than 0.05) basal AIB uptake in EPI and SOL, but the relative increases were greater in the obese rats (EPI 54% and SOL 71% vs. EPI 32% and SOL 37%). These results demonstrate that genetically obese Zucker rats have reduced basal skeletal muscle amino acid uptake and suggest that physical inactivity may partially contribute to this defect.

Amino Acids↗
PubMed1990

Increased hypothalamic content of preproneuropeptide Y messenger ribonucleic acid in genetically obese Zucker rats and its regulation by food deprivation.

Neuropeptide Y (NPY) is a potent orexigenic agent capable of producing hyperphagia and obesity. NPY-containing neurons project from the hypothalmic arcuate nucleus to the paraventricular nucleus, an area known to be sensitive to the orexigenic effects of NPY. In this study we investigated the possibility that preproNPY messenger RNA (mRNA) content may be altered in obese Zucker rats compared to that of their lean littermates. Total RNA was isolated from hypothalamic dissections from male and female, obese and lean Zucker rats. RNA was also isolated from dissections of: olfactory bulb, entorhinal cortex, hippocampus, and striatum of female obese and lean rats. PreproNPY mRNA content was determined by solution hybridization-RNase protection analysis. The results revealed a 2- to 3-fold increase in preproNPY mRNA levels in the hypothalamus of obese animals compared to lean. The increase was observed in both sexes and was specific to the hypothalamus. In situ hybridization localized this increase to the arcuate nucleus. An additional RNase protection study was pursued to investigate the effects of 72 h food deprivation on hypothalamic preproNPY mRNA levels in lean and obese animals. Lean animals displayed an approximate 2-fold increase in preproNPY mRNA content, whereas obese animals showed no significant increase after food deprivation. These data are consistent with the hypothesis that NPY projections within the hypothalamus are involved in regulating feeding behavior and weight gain, and that disturbed regulation of hypothalamic NPY expression may play a role in the etiology of obesity in the genetically obese Zucker rat.

Animals↗
PubMed1990

Mechanisms of impaired growth hormone secretion in genetically obese Zucker rats: roles of growth hormone-releasing factor and somatostatin.

GH secretion is markedly blunted in obesity; however, the mechanism(s) mediating this response remains to be elucidated. In the present study we examined the involvement of the two hypothalamic GH-regulatory hormones, GH-releasing factor (GRF) and somatostatin (SRIF), using the genetically obese male Zucker rat. Spontaneous GH, insulin, and glucose secretory profiles obtained from free moving, chronically cannulated rats revealed a marked suppression in amplitude and duration of GH pulses in obese Zucker rats compared to their lean littermates (mean 6-h plasma GH level, 3.9 +/- 0.4 vs. 21.5 +/- 3.8 ng/ml; P less than 0.001). Obese rats also exhibited significant hyperinsulinemia in the presence of normoglycemia. The plasma GH response to an iv bolus of 1 microgram rat GRF-(1-29)NH2, administered during peak and trough periods of the GH rhythm, was significantly attenuated in obese rats at peak (137.4 +/- 26.1 vs. 266.9 +/- 40.7 ng/ml; P less than 0.02), although not at trough, times. Passive immunization of obese rats with a specific antiserum to SRIF failed to restore the amplitude of GH pulses to normal values; the mean 6-h plasma GH level of obese rats given SRIF antiserum was not significantly different from that of obese rats administered normal sheep serum. Both pituitary wet weight and pituitary GH content and concentration were reduced in the obese group. Measurement of hypothalamic GRF immunoreactivity revealed a significant (P less than 0.05) reduction in the mediobasal hypothalamic GRF content in obese rats (503.2 +/- 60.1 pg/fragment) compared to that in lean controls (678.1 +/- 50.2 pg/fragment), although no significant difference was observed in hypothalamic SRIF concentration. Peripheral SRIF immunoreactive levels were significantly (P less than 0.01) elevated in both the pancreas and stomach of obese rats. These results demonstrate that the genetically obese Zucker rat exhibits 1) marked impairment in both spontaneous and GRF-induced GH release, which cannot be reversed by SRIF immunoneutralization, 2) significant reduction in pituitary GH concentration, 3) depressed hypothalamic GRF content, and 4) elevated gastric and pancreatic, but not hypothalamic, SRIF levels. The findings suggest that the defect in pituitary GH secretion observed in the genetically obese Zucker rat is due, at least partially, to insufficient stimulation by hypothalamic GRF, and that SRIF does not play a significant role.

Animals↗
PubMed1989

Obesity- and sex-related alterations in growth hormone messenger RNA levels.

The secretion of growth hormone (GH) is abnormal in genetically obese Zucker rats. Measurements of pulsatile GH release and circulating GH levels in lean (Fa/?) and obese (fa/fa) rats have shown that both are reduced in the latter. We have studied pituitary GH gene expression in order to understand the role of GH synthesis in this abnormality. Obese animals have lower pituitary GH mRNA levels than lean controls. Within each genotype a sex difference was observed with the female animals having lower GH mRNA levels than the males. It is unlikely that the GH abnormality is due to a generalized pituitary defect because prolactin mRNA levels were the same in all four groups of rats.

Animals↗
PubMed1989

Common clinical features as predictors of bacterial diarrhea in infants.

Identification of infants with bacterial diarrhea during the first year of life is important to limit potentially serious complications, but indications for stool leukocyte examination and culture are not well defined. The ability of three clinical features--temperature, history of blood in the stool, and stool frequency--to predict the presence of bacterial gastroenteritis was analyzed. Over a 1-year period, 108 (10.4%) bacterial pathogens were isolated from 1,035 infants aged less than 1 year with diarrhea. Bacterial culture was positive in 14.9% of cases from May to October, compared with 6.2% of cases from November to April. A history of blood in the stool was the best individual predictor with sensitivity of 39%, specificity of 88%, and a positive predictive value of 30%. Temperature greater than 39 degrees C had sensitivity of 34% and specificity of 85%; greater than or equal to 10 stools in 24 hours had sensitivity of 28% and specificity of 85%. Using combinations of factors, we identified (1) a group of patients at high risk for bacterial diarrhea (infants with two of the three factors studied); (2) a low-risk group (those with temperature less than or equal to 38 degrees C, less than 10 stools in 24 hours, and the absence of blood in the stool); and (3) a group at intermediate risk for bacterial diarrhea (all other patients). We recommend routine stool cultures for infants with a high-risk combination. Additional clinical and laboratory features, such as stool leukocytes, should be studied among patients in the intermediate-risk group.

Diarrhea, Infantile↗
PubMed1988

Immunocytochemical analysis of somatostatin in the hypothalamus of obese and non-obese Zucker rats.

Levels of growth hormone (GH) are reduced in the genetically obese Zucker rat, fa/fa, in comparison to lean littermates. In normal rats, GH release is regulated by stimulatory and inhibitory factors of hypothalamic origin. The present experiment focuses on hypothalamic somatostatin (SOM; growth hormone release inhibiting factor) in order to determine if abnormal hypothalamic SOM may be a correlate of depressed GH secretion in fa/fa rats. We compared immunocytochemical localization of hypothalamic SOM between 5 obese (fa/fa) Zucker rats and 5 non-obese littermates. Brain sections from pairs of animals were processed simultaneously. The distribution of SOM immunoreactive cell bodies in the hypothalamus agreed with previous reports. SOM-containing neurons in the periventricular area were counted and analyzed at 4 hypothalamic levels: (1) anterior to the suprachiasmatic nucleus (SCN); (2) through SCN; (3) between SCN and the ventromedial hypothalamic nucleus (VMH); and (4) through VMH. The greatest number of SOM-immunoreactive cell bodies was observed at levels (2) and (3). The numbers of SOM-containing cells did not differ significantly between obese and lean animals. No apparent difference in density of fiber staining was observed in the median eminence.

Animals↗
PubMed1988

Expression of hepatic microsomal cholesterol 7 alpha-hydroxylase activity in lean and obese Zucker rats.

The activity of hepatic microsomal cholesterol 7 alpha-hydroxylase was studied in genetically obese and lean Zucker rats. The liver microsomal cholesterol 7 alpha-hydroxylase activity in fatty Zucker rats (fa/fa) is about 50% to 70% lower than that of the lean (Fa/-) rats of the same sex, when animals were sacrificed at the middle of the dark cycle. When rats were sacrificed at the middle of the light cycle, cholesterol 7 alpha-hydroxylase activity was the same as in the dark cycle in obese rats of both sexes, but was 65% lower in lean rats. However, cholesterol 7 alpha-hydroxylase activity was stimulated by the treatment with cholestyramine in both obese and lean rats. Our results suggested that the diurnal regulation of cholesterol 7 alpha-hydroxylase activity is lost in obese rats but was present under cholestyramine treatment in the genetically obese strain of rats.

Animals↗
PubMed1987

An association between anti-inflammatory medication and internal pelvic fistulas.

Spontaneous internal fistulas involving intestine, rectum, bladder, or vagina in patients without predisposing illnesses were studied. Twelve of 20 (60 percent) were receiving steroids or other anti-inflammatory medication at the time the fistulas developed. Fifteen of the 20 patients subsequently had diverticular disease identified. It is proposed that there is an association between anti-inflammatory medication and fistulas that develop from intestine to other pelvic viscera, spontaneously or in association with colonic diverticula.

Adult↗
PubMed1987

Hypothalamo-spinal projections in the golden hamster.

The distribution of hypothalamic projections to the spinal cord in hamsters was determined using the retrograde tracers horseradish peroxidase (HRP) and wheat germ agglutinin-HRP (WGA-HRP). Large injections of HRP or WGA-HRP were made into the thoracic spinal cord of adult male golden hamsters. HRP-labeled neurons were observed primarily in the parvocellular division of the paraventricular nucleus and in the lateral hypothalamus. The organization of hypothalamo-spinal connections appears to be highly conserved in mammalian species.

Animals↗
PubMed1986

Long-term effects of diethylstilbestrol (DES) on genetically obese and non-obese female Zucker rats.

The long-term effects of diethylstilbestrol (DES) were studied in genetically obese and non-obese female Zucker rats. Experimental animals were implanted subcutaneously with a 15 mg pellet of DES at the beginning of the experiment, and again three months later. Weight-matched control animals received no treatment. Rats were sacrificed 6.5 months after the first implantation. The animals treated with DES had significantly lower body weights at sacrifice than the control rats; the percentage reduction was comparable for the obese and lean animals. Treatment was associated with significant reductions in body length, food intake, water intake and weights of an inguinal fat pad, heart, liver, kidneys and adrenals. In contrast, weight of the reproductive tract and pituitary gland were significantly higher in the treated rats. Effects of DES treatment were comparable in lean and obese rats.

Animals↗
PubMed1986

Growth hormone and prolactin secretion in genetically obese Zucker rats.

GH and PRL levels were measured by RIA in plasma samples taken from genetically obese and nonobese rats over a 6-h period at consecutive 15-min intervals. The mean GH level was 204 ng/ml for lean animals and 48 ng/ml for obese rats; the difference is significant (t = 5.8; P less than 0.01). For the group of 5 lean rats, there were 10 GH peaks that exceeded the upper limit of the assay (800 ng/ml), whereas for the group of 6 obese rats, there were only 2 peaks that exceeded the upper limit. In some of the obese rats, peaks of very small amplitude were present. No differences were seen in PRL levels. The mean plasma PRL level was 3.6 ng/ml for lean animals and 3.3 ng/ml for obese rats. Abnormalities in GH in obese rats may be related to an imbalance between hypothalamic releasing and inhibiting factors or a defect in the pituitary.

Animals↗
PubMed1985

Effect of opiates on the release of cholecystokinin from in vitro hypothalamus and frontal cortex of Zucker lean (Fa/-) and obese (fa/fa) rats.

Opiates, morphine and [D-Ala2-D-Leu5]-enkephalin (DADLE), inhibited the K+-stimulated release of cholecystokinin (CCK) from the hypothalamus of both Zucker obese (fa/fa) and lean (Fa/-) rats, in vitro. Morphine and DADLE did not inhibit the K+-stimulated release of CCK from frontal cortex from either strain. The opiates did not affect basal efflux of CCK and their effects were all blocked by equimolar concentrations of naloxone. These studies indicate a regional specificity for the effect of opiates on CCK release, and may provide evidence for a cellular mechanism by which endogenous opiates modulate feeding behavior.

Animals↗
PubMed1985

Evidence of incomplete behavioral sexual differentiation in obese male Zucker rats.

Genetically obese male Zucker rats displayed lower rates of intromission behavior and ejaculated in significantly fewer tests than lean Zucker littermates. After castration and daily injections of a low dosage (5 micrograms/kg) or estradiol benzoate (EB) followed by progesterone (1 mg/kg), obese males displayed significantly higher lordosis quotients than lean controls. Continued daily administration of higher (10, 15 micrograms/kg) dosages of EB followed by progesterone caused significant reductions in lordotic responsiveness in obese males but not in lean controls. Thus, deficient masculine coital performance was correlated with altered receptive responsiveness to ovarian steroids in obese Zucker male rats. This suggests that the sexual differentiation of the developing brain may be deficient in obese Zucker males.

Animals↗
PubMed1985

Effect of dopamine agonists and fenfluramine on discriminative behavior in obese and lean Zucker rats.

Dopamine agonists and fenfluramine were used as pharmacological probes to investigate the possible difference in sensitivity and time course of drug action in genetically obese Zucker rats and their lean littermates. All rats were trained to discriminate between the stimulus properties of 0.6 mg/kg d-amphetamine and its vehicle in a two-lever, food-motivated operant task. Once trained, both groups of rats showed a dose-related decrease in discriminative performance with lower amphetamine doses. Analysis of the dose-response curves indicated an ED50 for the obese rats of 0.17 mg/kg and for the lean group of 0.14 mg/kg. Administration of 0.3-1.2 mg/kg l-amphetamine and 2.5-10.0 mg/kg cocaine produced a pattern of responding similar to that observed with d-amphetamine. In contrast, 0.08-mg/kg apomorphine produced saline-appropriate responding and 1.5-2.5 mg/kg fenfluramine produced intermediate results in both groups. Time-course experiments indicated that the lean rats maintain errorless discriminative performance through 90 min post-injection, whereas the obese rats discriminate d-amphetamine significantly less at that post-administration time. The results suggest a similar sensitivity to d-amphetamine and other dopaminergic agonists in obese and lean rats with a difference in the time-course of d-amphetamine's action between these two groups.

Amphetamine↗
PubMed1985

Left ventricular function of the isolated, genetically obese rat's heart.

We sought to determine if left ventricular (LV) function of the heart from the adult, chronically obese animal is impaired. Hearts from 50 wk-old genetically obese female Zucker rats (624 +/- 13 g) and their lean littermate controls (275 +/- 5 g) were isolated during ether anesthesia, supported metabolically by retrograde aortic perfusion (6 ml/min, 35 degrees C) with physiological solution containing suspended canine erythrocytes (hematocrit, 20%), and the ventricles were paced at 180 beats/min. A distensible, fluid-filled balloon was placed in the LV, and pressure-volume (PV) relationships were obtained. The obese and lean end-diastolic PV curves were not different, and therefore the obese and lean LV chamber compliances were similar. Comparison of the systolic PV relationships demonstrated that the obese rat's heart had a greater pressure-generating capability, which probably was a reflection of its increased LV mass (0.96 +/- 0.03 vs. 0.72 +/- 0.02 g). The calculated average meridional (or circumferential) peak systolic wall stress in the LV of the obese rat's heart, however, was significantly reduced compared with control. This diminished ability to develop systolic stress from the same end-diastolic volumes suggests that the hypertrophied LV of the middle-aged obese rat's heart is dilated or that its contractility is depressed, or both.

Animals↗