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Biomedical subjects

J Hirsch

Publications and source records attributed to J Hirsch.

At least 145 records · Page 8Linked to original sources
PubMed1991

Food deprivation and hypothalamic neuropeptide gene expression: effects of strain background and the diabetes mutation.

We have used a novel method to identify genes expressed in the hypothalamus which may be potentially involved in controlling food intake and energy metabolism. We assumed that food deprivation, a powerful stimulus of food intake, would stimulate the activity of neural pathways involved in feeding behavior which should be reflected in an increase in the synthesis of any relevant neuropeptide and its messenger RNA. A study of 5 neuropeptides in 5 strains of mice has identified neuropeptide Y (NPY) as a gene whose expression in the hypothalamus is controlled by nutritional status, suggesting that hypothalamic NPY neurons are a link in the neural network regulating feeding behavior and energy metabolism. In addition, we have studied the effect of the diabetes mutation on neuropeptide gene expression during fasting and refeeding. Our findings suggest that abnormal NPY and enkephalin gene expression in the hypothalamus may be two important determinants of the expression of the diabetes mutation.

Animals↗
PubMed1991

Food deprivation and age modulate neuropeptide gene expression in the murine hypothalamus and adrenal gland.

We have developed a rapid and simple method for quantitative Northern blot analysis of rare messenger RNA species from single mouse hypothalami and adrenals. This technique has allowed us to study the effects of food deprivation on neuropeptide gene expression in the mouse hypothalamus and adrenal gland. The potential modulatory effects of sex and age were also investigated. Food deprivation induced a two-fold increase in the amount of hypothalamic neuropeptide Y (NPY) mRNA, but did not increase NPY mRNA in the brainstem. Age had a significant effect on levels of NPY messenger RNA levels in the hypothalamus. However, there were no gender-associated effects. Sexually immature females (6 weeks old) had higher levels of NPY expression than mature females (9 weeks old). In contrast, in the adrenal gland, increasing maturity was associated with higher levels of NPY mRNA. As in the hypothalamus, fasting caused approximately two-fold increases in NPY mRNA over levels in the ad libitum fed state for both mature and immature mice. Thus, hypothalamic NPY neurons are responsive to nutritional deprivation and developmental status, suggesting that NPY neurons may be important in energy homeostasis.

Adrenal Glands↗
PubMed1991

Assessment of potential contrast sensitivity. Part I: Preoperative prediction of contrast sensitivity following intraocular lens implantation.

Preoperative contrast sensitivity functions (CSFs) were determined for 15 cataract patients using laser-generated patterns that effectively bypassed the optical components of the eye. These functions were compared with postoperative CSFs determined using traditional methods by transmission through the optics of the eye. Accurate prediction of postoperative contrast sensitivity occurred in 91% of the cases (ten of 11) for patients with preoperative visual acuity of 20/200 or better and in 67% of all the cases (ten of 15). Prediction failures occurred when the laser interferometer was not able to penetrate the cataract or when postoperative complications occurred. These results suggest that preoperative measurement of laser interferometric CSF is a useful predictor of postoperative CSF for patients with mild to moderate cataracts that can be bypassed by the laser and with better than 20/200 preoperative visual acuity. The problem of assessment when lens opacity is advanced is addressed in Part II.

Aged↗
PubMed1991

Assessment of contrast sensitivity. Part II: The relationship between objective lens opacity and laser interferometric contrast sensitivity in the cataract patient.

The laser interferometer can effectively bypass the optics of the eye and measure retinal function in patients with immature cataracts. However, it is not known how much laser interferometric measurements are impaired by cataract density. In this study we compared objective lens opacity using the IntraOptics opacity lensmeter with contrast sensitivity (CS) measured by a Randwal He-Ne laser interferometer. Comparison of lens opacity with CS in the cataract population revealed an inverse linear relationship between objective lens opacity and retinal contrast sensitivity. Separation by cataract type showed correlation coefficients as high as -0.91 for nuclear sclerotic predominant cataracts and as low as no significant correlation for posterior subcapsular predominant cataracts. Comparisons of before and after implantation surgery contrast sensitivities (as measured by the laser interferometer) with preoperative lens opacities (as measured by the IntraOptics opacity lensmeter) quantified the extent to which laser interferometric measurements underestimated potential retinal function. We found that for all cataracts, other than posterior subcapsular predominant cataracts, potential contrast sensitivity (in decibels) was underestimated by about 0.2 to 0.3 times the opacity measured by this technique.

Adult↗
PubMed1991

Effects of early pregnancy on regional adipose tissue metabolism.

Adipose tissue metabolism was studied in needle biopsies from femoral and abdominal subcutaneous depots, in 12 healthy young women, during early (9-11 weeks) pregnancy, and 6 weeks after a legal abortion. Both during pregnant and non-pregnant conditions, a higher lipoprotein lipase (LPL) activity was seen in the femoral compared to the abdominal region, but the LPL activity was not influenced by early pregnancy. Rates of fatty acid esterification and acylglyceride synthesis were not different between regions, nor affected by pregnancy. The stimulatory effect of norepinephrine (10(-7) M) on lipolysis was significantly greater in the abdominal than in the femoral region in both the pregnant and non-pregnant condition. This difference was apparently due to higher alpha-adrenergic activity in the femoral region. Pregnancy per se had no effect on lipolytic response to norepinephrine. These findings indicate that lipid accumulation is favoured in the femoral region in young women both during pregnant and non-pregnant conditions.

Abdomen↗
PubMed1991

Correlation of isomeric fatty acids in human adipose tissue with clinical risk factors for cardiovascular disease.

The relationships between the adipose tissue concentrations of 19 geometric and positional fatty acid isomers and 10 cardiovascular disease risk factors were determined in 76 free-living adult males. The percentages for trans isomers (total mean +/- SD 4.14 +/- 0.97%) and cis isomers (total mean +/- SD 2.91 +/- 0.34%) in adipose tissue generally agreed with dietary estimates based on the consumption of hydrogenated oils. A major exception was the percentage of 11c-18:1, which was twofold higher in adipose tissue. The total level of fatty acid isomers in adipose tissue or a factor (derived by factor analysis) that was representative of isomers of dietary origin was not significantly correlated with the cardiovascular risk factors. Only three trans isomers (11t-18:1, 12t-18:1, and 5t-14:1) and three cis isomers (11c-18:1, 13c-18:1, and 7c-16:1) were weakly correlated either positively or negatively with age, body mass index, plasma and lipoprotein cholesterol, and/or blood pressure (P less than 0.05, r greater than 0.231).

Adipose Tissue↗
PubMed1991

Changes in abdominal and gluteal adipose-tissue fatty acid compositions in obese subjects after weight gain and weight loss.

The fatty acid compositions of abdominal and gluteal subcutaneous adipose tissues of eight obese subjects were measured after an initial 5-10-wk period of weight maintenance on a liquid-formula diet (40% of calories as corn oil, 45% as carbohydrate, and 15% as protein), after a 10% increase in weight (11-20 kg) on a solid-food diet of each subject's choice (n = 5) or after a 20% decrease in weight (26-37 kg) on 800 kcal/d of the same corn-oil-formula diet (n = 5). After weight gain or weight loss, all subjects maintained their new weights for 2-10 wk on the same corn-oil-formula diet. As hypothesized, there were minimal changes in the concentrations of 41 fatty acids identified in both abdominal and gluteal tissues after all dietary phases, and small site-specific differences in the levels of saturated and monounsaturated fatty acids were not altered. The largest change was a 15% decrease (P less than 0.05) in 18:3n-3 in both abdominal and gluteal tissues during weight loss, despite higher levels in the diet than in the baseline adipose tissue. This decrease occurred without coexisting decreases in 22:5n-3 and 22:6n-3, two elongase-desaturase products of 18:3n-3 that were not detectable in the diet.

Abdomen↗
PubMed1991

Adipose-tissue fatty acid composition in recipients of long-term total parenteral nutrition (TPN).

Adipose-tissue fatty acid composition was studied in nine patients requiring long-term total parenteral nutrition (TPN). The patients received 17 +/- 8% of total energy as soybean-oil emulsion (Intralipid) and 66 +/- 8% as glucose. Despite low intake of 9c-16:1, 11c-18:1, and 13c-18:1, adipose-tissue concentrations of these monounsaturated fatty acids were higher in the TPN patients than in free-living control subjects (P less than 0.05) and inversely correlated with the percent energy from fat (r = -0.56, P = 0.11; r = -0.64, P = 0.06; r = -0.81, P = 0.008, respectively). This suggests that these fatty acids accumulated from endogenous synthesis from carbohydrate and thus may be markers of the percent fat in the diet. The essential fatty acids, 18:2 and 18:3n-3, positively correlated with the percent energy from fat (r = 0.79, P = 0.01; r = 0.80, P = 0.01, respectively). Linear-regression analysis suggests that normal adipose-tissue stores of 18:2 and 18:3n-3 are maintained when intravenous soybean-oil emulsion provides 11-20% and 4-12%, respectively, of total energy.

Adipose Tissue↗
PubMed1991

Metabolic and hemodynamic responses to endogenous and exogenous catecholamines in formerly obese subjects.

Formerly or reduced-obese (RO) subjects exhibit diminished systemic energy requirements for weight maintenance. Based on studies in animals and humans, there is reason to believe that the autonomic nervous system (ANS) plays an important role in coordinate regulation of energy metabolism and may be altered in the RO state. We have, therefore, investigated aspects of autonomic physiology in obese (OB), RO, and never obese (NO) subjects subjected to insulin-mediated hypoglycemia and incremental intravenous infusions of epinephrine. Total catecholamine secretion during insulin-induced hypoglycemia was significantly lower in the RO. The RO showed increased sensitivity to in vivo lipolytic and cardiovascular effects of endogenous and infused catecholamines. In these studies, OB subjects responded more like the NO subjects than did the RO. The RO display characteristic changes in autonomic status that may play a role in their enhanced energy efficiency.

Adult↗
PubMed1991

Heart rate variability as a measure of autonomic function during weight change in humans.

Changes in autonomic function were studied during experimentally induced weight changes in seven subjects. A spectral analysis of heart rate variability (HRV) was used to evaluate autonomic activity during weight change. With a 10% increase in body weight above the usual or starting weight, there was a decline in parasympathetic power accompanied by a rise in mean heart rate. Heart rate declined during weight reduction, but the power of HRV did not change significantly. Because heart rate power at the frequency of respiratory rate can be affected by respiratory rate, three additional subjects were tested at a constant respiratory rate. Weight increases in this group also led to a decline in the power of HRV at a frequency attributable to the parasympathetic nervous system. Such a parasympathetic effect of weight increase may be one mechanism for the arrhythmias and other cardiac alterations that accompany obesity.

Adult↗
PubMed1991

Regional differences in adrenoreceptor status of adipose tissue in adults and prepubertal children.

The relative anatomical distribution of adipose tissue in central (abdominal) vs. peripheral (extremity) depots is highly correlated with the risk of adiposity-related morbidities, such as hypertension, cardiovascular disease, and diabetes mellitus. In adults, comparisons of the functional status of plasma membrane adrenergic receptors indicate that abdominal adipocytes are more responsive to the lipolytic action of beta 1-adrenergic agonists, while gluteal adipocytes are more responsive to the antilipolytic action of alpha 2-adrenergic agonists. To determine whether such regional differences in adipocyte adrenoreceptor status are present before puberty, we obtained needle biopsy samples of abdominal and gluteal sc adipose tissue in the post-absorptive state from 13 prepubertal children and 47 adults of varying body compositions (obese vs. lean). Lipolysis rates were measured in the basal state and in the presence of 10(-7) M norepinephrine (a mixed alpha- and beta-adrenergic agonist) and 10(-7) M isoproterenol (a beta-adrenergic agonist). In children, there were no significant regional differences in either the basal rate of lipolysis or the responses to adrenergic lipolytic and antilipolytic stimuli. In lean and obese adults, gluteal sc adipose tissue was strikingly more responsive to antilipolytic alpha-adrenergic stimulation (P less than 0.0001) and less responsive to lipolytic beta-adrenergic stimuli (P less than 0.005) compared to abdominal tissue. Abdominal sc adipocytes from children had a significantly lower rate of basal lipolysis (P less than 0.01) and were more responsive to alpha 2-adrenergic (antilipolytic) stimuli (P less than 0.05) than abdominal adipocytes in adults. These results suggest that peripubertal endocrine changes may mediate the striking regional differences in adrenoreceptor status of adult adipose tissue, and that a decrease in the preponderance of alpha 2-receptors (antilipolytic) in abdominal adipose tissue may account in part for the relative loss of central vs. peripheral fat that occurs during puberty.

Adipose Tissue↗
PubMed1991

Stability of nizatidine in total nutrient admixtures.

The stability of nizatidine in total nutrient admixtures (TNAs) and the effect of the drug on the stability of lipid emulsions in the TNAs were studied. Duplicate 1476-mL amino acid-dextrose base solutions were prepared; nizatidine 300 mg was added to one. TNAs were prepared by adding to 75-mL samples of the base solutions Intralipid (KabiVitrum) or Liposyn II (Abbott) and sterile water as needed to achieve final lipid concentrations of 3% and 5%. Triplicate 100-mL samples for each lipid product and concentration were prepared; fat-free samples containing nizatidine were also studied. The theoretical final nizatidine concentration was 150 micrograms/mL. Samples were stored at 22 degrees C for 48 hours. Initially and at 12, 24, and 48 hours, the samples were visually inspected, tested for pH and particle-size distribution, and assayed by high-performance liquid chromatography for nizatidine concentration. No color change, precipitation, creaming, or oiling out was noted. For the 12 TNAs containing nizatidine, mean solution pH during the study was 5.88; stability of the lipid products requires pH values greater than or equal to 5.5. Particle-size distribution did not differ appreciably between the nizatidine-containing and drug-free TNAs. Nizatidine concentrations remained greater than 90% of the initial concentration. Nizatidine at a theoretical concentration of 150 micrograms/mL was stable for 48 hours at 22 degrees C in TNA solutions containing 3% and 5% Intralipid or Liposyn II and did not appear to affect lipid emulsion stability.

Chromatography, High Pressure Liquid↗
PubMed1990

Hydrolysis of (1----3)- and (1----2)-beta-D-xylosidic linkages by an endo-(1----4)-beta-D-xylanase of Cryptococcus albidus.

The substrate specificity of an endo-(1----4)-beta-D-xylanase of the yeast Cryptococcus albidus was investigated using a series of methyl beta-D-xylotriosides. In addition to (1----4) linkages, the enzyme could cleave (1----3) and (1----2) linkages adjacent to a (1----4) linkage and further from the non-reducing end of the substrate. The enzyme could hydrolyse a (1----3) linkage that attached a terminal xylopyranosyl group to a (1----4)-linked xylobiosyl moiety. The enzyme did not attack alpha-D-xylosidic linkages. The rate of cleavage of (1----4) linkages was much higher than those of other linkages at 0.5mM substrate, but the rates were comparable at 20mM substrate when transglycosylation reactions also occurred that facilitated degradation of the substrates.

Carbohydrate Conformation↗
PubMed1990

Meiotic gene conversion and crossing over: their relationship to each other and to chromosome synapsis and segregation.

The yeast mer1 mutant produces inviable spores and is defective in both meiotic recombination and chromosome pairing. A gene called MER2 partially suppresses the mer1 phenotype when present in high copy number. Both gene conversion and chromosome pairing are completely restored in mer1 strains overexpressing MER2; however, reciprocal crossing over and spore viability are not restored. The data presented are consistent with a model in which chromosome pairing is a direct consequence of a homology search mediated through gene conversion. Analysis of random viable spores indicates that the crossovers that occur in mer1 strains overexpressing MER2 are more effective in ensuring meiosis I disjunction than those that occur in mer1 strains. One interpretation of this result is that only those crossovers that occur in the context of the synaptonemal complex lead to the establishment of functional chiasmata. The MER2 gene product is essential for meiosis.

Cell Nucleus↗
PubMed1990

Solution behavior of methyl beta-xylobioside: conformational flexibility revealed by n.m.r. measurements and theoretical calculations.

The conformations of methyl beta-xylobioside in solution have been determined by n.m.r. spectroscopy. Interglycosidic 3JC,H values and the chemical shifts of the 13C resonances were measured at various temperatures in the range 238-378 K for solutions in 1,4-dioxane, methanol, methyl sulfoxide, and water. The temperature and solvent dependencies of the data obtained suggest conformational flexibility. Quantum-chemical PCILO calculations, with evaluation of the solvent effects, and molecular mechanics calculations revealed the existence of 7 low-energy regions for which the geometries and energies were determined. The computed abundances of conformers and averaged J values accord with the experimental data.

Carbohydrate Conformation↗