Case of the season. Silo filler's disease in a patient with prior Swyer-James syndrome.
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Adult↗
Biomedical subjects
J Hirsch
Publications and source records attributed to J Hirsch.
The economic impact of 5-HT3 receptor antagonists.
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Cost-Benefit Analysis↗
pH-sensitive K+ channels in the distal nephron.
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Animals↗
In vitro lipid synthesis in human adipose tissue from three abdominal sites.
The association between abdominal deposition of adipose tissue and morbidities accompanying obesity may be related to high rates of free fatty acid release from enlarged intra-abdominal stores. To investigate cellular mechanisms that might contribute to enlargement of intra-abdominal adipocytes, lipolysis, triacylglycerol (TG), and diacylglycerol (DG) synthesis from [14C]glucose was measured in abdominal subcutaneous, omental, and mesenteric adipose tissue from severely obese women and men. Subcutaneous adipose tissue from women showed the highest rates of TG synthesis compared with the intra-abdominal site, or any site in men. isoproterenol stimulated TG synthesis more in intra-abdominal than subcutaneous adipose tissue. In the basal state, intra-abdominal adipose tissue from both men and women showed rates of [14C]DG accumulation approximately 50% total [14C]acylglyceride accumulation, whereas, in subcutaneous adipose tissue, [14C]DG accumulation was approximately 25% of total. Basal lipolysis was lower in intra-abdominal than subcutaneous adipocytes. Stimulation of lipolysis reduced [14C]DG accumulation more in intra-abdominal than subcutaneous adipose tissue. Low rates of acylglyceride synthesis in intra-abdominal adipocytes may prevent accumulation of large intra-abdominal fat stores in women.
Abdomen↗
The Zucker fatty (fa) gene is not a mutation of corticotropin-releasing factor.
Corticotropin-releasing factor (CRF) appears to regulate several physiological systems that display prominent abnormalities in Zucker fatty (fa/fa) rats, including the hypothalamic-pituitary-adrenal axis, the autonomic nervous system, and feeding behavior. Moreover, central administration of CRF ameliorates the obese phenotype. In light of these observations, the gene for CRF is a plausible candidate for the defective gene in the Zucker fatty rat. We report here the use of molecular genetic linkage analysis to test the hypothesis that fa is a mutant allele of the CRF gene. A restriction fragment length polymorphism for CRF between Zucker (13M) and Brown Norway (BN) DNA allowed us to examine segregation of 13M and BN CRF alleles relative to fa in 58 obese (fa/fa) F2 progeny of a 13MBN fa/+F1 intercross. If fa = CRF, all animals homozygous for the fatty mutation should be homozygous for the 13M CRF allele. However, only 10/58 fa/fa animals were homozygous for the 13M CRF allele, indicating that fa and CRF are not allelic. Thus, although CRF may be important in the physiology of Zucker rat obesity, fa is not a CRF mutation. Using a mouse C57BL/6J Spretus F1 x C57BL DBA/2J F1 intercross, we were able to demonstrate that the mouse CRF gene is linked to the carbonic anhydrase II (Car-2) gene on mouse chromosome 3, in a region of synteny-homology with rat chromosome 2. Thus the rat CRF gene is probably located on chromosome 2.
Animals↗
A molecular genetic method for genotyping fatty (fa/fa) rats.
After three decades of physiological research, the precise nature of the genetic lesion in Zucker fatty (fa/fa) rats remains unknown. Several methods have been used to identify preobese rats to detect the earliest phenotypic effects of the fa mutation. Most of these methods have used phenotypic characteristics that are not reliable until the second week of life, when increased adiposity is already evident. We have used a restriction fragment length polymorphism (RFLP) for a human genomic DNA probe (VC85) that is tightly linked to the fa locus on rat chromosome 5 to genotype the F2 progeny of a Zucker (13M) x Brown Norway (BN) fa/+ F1 intercross. Sixty-four rats, comprising five litters, were killed at 5-6 wk of age. DNA was isolated either from tail at age 4-7 days (36 rats) or from organs at the time of death (28 rats). Adiposity was scored using inguinal fat pad weight as a percentage of body weight. RFLP analysis was > 99% accurate in identifying obese (fa/fa) rats. This molecular genetic method can be used to genotype fatty rats from an appropriate genetic cross at any age, even prenatally. Moreover, this method can distinguish heterozygous from homozygous littermates, enabling an analysis of gene dosage effects.
Adipose Tissue↗
Lack of beta 3-adrenergic effect on lipolysis in human subcutaneous adipose tissue.
Human adipocytes are responsive to both alpha- (antilipolytic) and beta-(lipolytic) actions of catecholamine agonists. These effects are mediated by G proteins which interact with adenylcyclase beta 1- and beta 2-adrenoreceptor (AR) subtypes are identified in human adipose tissue. The existence of a third beta-adrenergic (beta 3) receptor has been recently proposed. The beta 3-AR has been reported to mediate catecholamine-induced cAMP accumulation and to be more responsive in this regard than either the beta 1- or the beta 2-AR. To examine the possibility that a beta 3-AR plays a significant role in the control of catecholamine-stimulated lipolysis in human adipose tissue, we used a sensitive in vitro measure of lipolysis. Abdominal and gluteal sc adipose tissue samples from 14 adults were incubated with isoproterenol, a nonspecific beta-AR agonist which activates adenylyl cyclase via all three beta-AR subtypes, in the presence of varying concentrations of a beta-AR antagonist, alprenolol, which blocks the beta 1- and beta 2-AR, but not the beta 3-AR. In tissue from both abdominal and gluteal sites, alprenolol (10(-3) M) completely abolished the lipolytic response to isoproterenol (10(-6) M). Alprenolol (10(-3) M) alone reduced basal lipolysis by 10.2 +/- 2.2% (SEM) in abdominal tissue (P < 0.01), and 7.1 +/- 2.7% in gluteal tissue (P < 0.05). In the presence of alprenolol (10(-3) M), isoproterenol (10(-6) M) had no demonstrable lipolytic effect. The probability of incorrect acceptance of the null hypothesis that isoproterenol had no effect on lipolysis in alprenolol-blocked tissue is P beta < 0.05 for both depots. As an additional control, pooled inguinal adipose tissue from adult male Sprague-Dawley rats was incubated with the same concentrations of alprenolol. Rat adipose tissue has been previously shown to express the beta 3-adrenoreceptor and lipolysis was increased in rat adipose tissue in the presence of alprenolol 10(-4) M and 10(-5) M. We conclude that beta 3-ARs, if present in human adipocyte plasma membranes, do not significantly affect rates of lipolysis.
Abdomen↗
Venovenous compares favorably with venoarterial access for extracorporeal membrane oxygenation in neonatal respiratory failure.
Traditional extracorporeal membrane oxygenation via the venoarterial route requires cannulation and ligation of the internal jugular vein and common carotid artery. Concerns about ligation of the common carotid artery prompted development of a 14F double-lumen internal jugular vein cannula for venovenous oxygenation for neonates with respiratory failure. We retrospectively compared 22 patients supported by venovenous bypass and 20 patients supported with traditional venoarterial bypass. The two groups of patients were selected to be comparable in terms of diagnosis and severity of respiratory insufficiency. The diagnoses in both groups were limited to meconium aspiration syndrome or persistent pulmonary hypertension of the newborn. The average oxygenation indexes in the two groups were similar (46.6 venovenous, 47.2 venoarterial, p = not significant). Venovenous access allowed flow rates of more than 100 ml/kg per minute, which were adequate for gas exchange support. One patient required conversion from venovenous to venoarterial bypass because of hemodynamic instability. The average time of bypass support was 115 hours (range 24 to 338 hours) for venovenous bypass and 134 hours (range 47 to 361 hours) for venoarterial bypass (p < 0.05). The time to extubation after decannulation from extracorporeal membrane oxygenation was 133 hours (range 38 to 720 hours) for venovenous support and 100 hours (range 27 to 192 hours) for venoarterial support (p = not significant). One patient supported with venoarterial bypass had an intracranial hemorrhage. There were no documented neurologic injuries in the patients managed with venovenous bypass. There were no deaths in either group. Venovenous extracorporeal membrane oxygenation through a double-lumen cannula can adequately provide respiratory support for neonates with pulmonary failure and effectively avoids ligation of the common carotid artery.
Carotid Artery, Common↗
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↗
The reaction of 3-deoxy-D-glycero-pentos-2-ulose ("3-deoxyxylosone") with aminoguanidine.
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Guanidines↗
[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↗