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Biomedical subjects

J Hirsch

Publications and source records attributed to J Hirsch.

At least 19 recordsLinked to original sources

The reaction of some dicarbonyl sugars with aminoguanidine.

The reactions of aminoguanidine (guanylhydrazine) with 3-deoxy-D-erythro-hexos-2-ulose (1a), 3-deoxy-D-glycero-pentose-2-ulose (1b), D-erythro-hexos-2-ulose (1c), and D-glycero-pentose-2-ulose (1d) were examined at 37 degrees at a solution pH of 7.0 (phosphate buffer). For 1a and 1b, two major products were observed and shown respectively to be the 5- and 6-substituted 3-amino-1,2,4-triazine derivatives. The ratios of the products were independent of the amount of aminoguanidine present or the order of mixing the reagents prior to the experiments. For 1c and 1d, only the 5-substituted triazine derivatives were formed. No evidence for hydrazone or bishydrazone formation was observed.

Guanidines

A center-of-mass computation describes the precision of random dot displacement discrimination.

We test three specific models of how the human visual system computes a just-noticeable-difference (jnd) in spatial separation. The strategies employed by these three models range from strictly local to global, and use a new discrimination task that measures the precision with which displacements of random dots in random dot arrays can be detected. Fits of these models to the data convincingly exclude the two most local models where the displacement discrimination is based on either point-to-point or bin-to-bin measurements of local dot positions. However, the data are consistent with a model where displacement discrimination is based on a globally computed center-of-mass parameter. This finding enlarges current views of what determines the precision of spatial discrimination to include the effects of stimulus complexity (number of dots) and multiplicity (number of dots displaced).

Differential Threshold

Selection for conditionability in Drosophila melanogaster.

Successful bidirectional selective breeding of Drosophila melanogaster for excitatory conditionability is reported, using the reliable measures of individual differences (first described by Holliday & Hirsch, 1984, 1986a, 1986b) to test 1,324 animals. Bidirectional selective breeding for good and poor conditioning has produced, respectively, one population in which the percentage of animals showing good conditioning has increased over 25 generations from 19% to 77% and another in which it has decreased over 23 generations to 0%-4%. No increase in a measure of sensitization induced by an unconditioned stimulus (the central excitatory state) accompanied the increase in the percentage of good conditioners in the population selected for good conditioning, whose level of conditioned responding exceeds that of the sensitization measure.

Animals

A clinical perspective on peptides and food intake.

Viewed from a clinical perspective, it is difficult to generate enthusiasm for the likelihood of finding a peptide that could be helpful in the treatment of obesity. A deeper understanding of obesity, as will emerge from molecular biology, is more likely to point the way to a useful peptide than further evaluations of the clinical dilemmas posed by obesity. However, a clinical perspective may be useful in pointing the way to a system that needs to be examined by molecular biology and also to inject caution in the evaluation of early findings when peptides are used in treatment.

Adipose Tissue

Energy intake required to maintain body weight is not affected by wide variation in diet composition.

Diets rich in fat may promote obesity by leading to a greater deposition of adipose-tissue triglycerides than do isoenergetic diets with less fat. This possibility was examined by a retrospective analysis of the energy needs of 16 human subjects (13 adults, 3 children) fed liquid diets of precisely known composition with widely varied fat content, for 15-56 d (33 +/- 2 d, mean +/- SE). Subjects lived in a metabolic ward and received fluid formulas with different fat and carbohydrate content, physical activity was kept constant, and precise data were available on energy intake and daily body weight. Isoenergetic formulas contained various percentages of carbohydrate as cerelose (low, 15%; intermediate, 40% or 45%; high, 75%, 80%, or 85%), a constant 15% of energy as protein (as milk protein), and the balance of energy as fat (as corn oil). Even with extreme changes in the fat-carbohydrate ratio (fat energy varied from 0% to 70% of total intake), there was no detectable evidence of significant variation in energy need as a function of percentage fat intake.

Adult

Effects of systemic growth hormone (GH) administration on regional adipose tissue in children with non-GH-deficient short stature.

Chronic administration of exogenous GH to GH-deficient children is associated with a selective depletion of the abdominal sc fat depot and a resultant relative increase in gluteal, relative to abdominal, adipocyte lipid content. In GH-deficient children, the degree of this change in relative lipid content per adipocyte appears to be correlated with decreases in sensitivity of abdominal subcutaneous fat to the antilipolytic action of insulin. We studied abdominal and gluteal sc adipose tissue from 10 children with short stature (height less than 5% ile, growth velocity less than 5 cm/yr, bone age delayed at least 2 yr), who were not GH deficient based upon provocative testing (non-GH-deficient short stature) 1) before beginning and 2) after 3 months of therapy with exogenous GH (Humatrope, 0.1 mg/kg sc 3 times/week). In abdominal and gluteal adipocytes, we measured lipid content, rates of reesterification of fatty acids released by ongoing lipolysis and rates of in vitro lipolysis and lipogenesis in response to insulin, adenosine, and various adrenoreceptor agonists. These biochemical measures were correlated with measures of statural growth and adipose tissue distribution in each subject. We found that GH therapy was associated with a significant reduction in abdominal adipocyte size (0.48 microgram +/- 0.08 lipid per cell prior to therapy vs. 0.43 microgram +/- 0.08 lipid per cell after therapy, P less than 0.05) and a significant increase in responsiveness of gluteal sc adipose tissue to the lipogenic actions of insulin. The significant correlations of changes in abdominal adipocyte volume with changes in regional adipose tissue insulin sensitivity that were noted in GH-deficient children were not noted in this subject population, perhaps due to effects of endogenous GH on pretreatment insulin responsiveness of adipose tissue. These data reaffirm that GH has site-specific effects on regional adipose tissue depots.

Abdomen

[Psychiatry for the elderly--a specialty field in progress].

Services concerned specially with elderly people who are mentally ill have developed in response to changing needs and expectations in society. In Norway, more than 600 beds in psychiatric hospitals are allocated to geriatric psychiatry (gerontopsychiatry), and are served by 20 senior registars and 19 psychiatric trainees. There are hardly any outreach programmes. Most of the beds in the hospitals are occupied by long-term psychiatric patients. There is little consensus as to what type of patients these beds should primarily serve. The authors recommend that a special unit to deal with geriatric psychiatry be organized in every county in Norway. Funds should also be allocated for professorships in this field.

Aged

Nuclear Overhauser effects and the flexibility of saccharides: methyl beta-xylobioside.

The behavior of methyl beta-xylobioside has been analysed by 1H-n.m.r. spectroscopy for solutions in water and methanol in the range - 15 degrees to 85 degrees. Experimental n.O.e. values did not change with temperature and solvent in contrast to the inter-glycosidic 3JC,H values. Experimental n.O.e. data accorded with the values calculated from time-averaged cross-relaxation terms. The tumbling times were determined from relaxation data and were in the sub-ns range.

Carbohydrate Conformation

Spatial and temporal distribution of pheromone biosynthesis-activating neuropeptide in Helicoverpa (Heliothis) armigera using RIA and in vitro bioassay.

A [3H]-PBAN (pheromone biosynthesis-activating neuropeptide) analog was synthesized, and binding of the radioligand to a specific PBAN-antiserum was achieved. The inhibition of binding of the radioligand by unlabeled PBAN, several PBAN analogs, and other competitors was studied and a specific radio-immunoassay was developed. Using this radioimmunoassay we found PBAN-like immunoreactivity in methanol extracts of hemolymph and neural tissues from females. Higher levels of PBAN-like immunoreactivity in extracts of brain-suboesophageal ganglion complexes, corpora cardiaca, thoracic ganglia, and abdominal ganglia were observed during the 4-5th h scotophase when compared to the PBAN-like immunoactivity levels during the 6-11th h photophase. On the other hand, the concentrations of PBAN-like immunoreactivity, in the terminal abdominal ganglion were higher during the photophase relative to minimal levels observed during the scotophase, indicating an accumulation before the onset of pheromone production. These differences in concentrations of PBAN were also reflected in the stimulation of in vitro pheromone glands, whereby significant stimulations were obtained by scotophase and photophase brain extracts, scotophase thoracic ganglia extracts, and photophase terminal abdominal ganglia extracts. No detectable levels of PBAN were found in hemolymph extracts during the sampling periods.

Amino Acid Sequence

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

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

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

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

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

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

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

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