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Biomedical subjects

J Hirsch

Publications and source records attributed to J Hirsch.

At least 91 records · Page 5Linked to original sources
PubMed1996

Activated partial thromboplastin time and outcome after thrombolytic therapy for acute myocardial infarction: results from the GUSTO-I trial.

BACKGROUND: Although intravenous heparin is commonly used after thrombolytic therapy, few reports have addressed the relationship between the degree of anticoagulation and clinical outcomes. We examined the activated partial thromboplastin time (aPTT) in 29,656 patients in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO-I) trial and analyzed the relationship between the aPTT and both baseline patient characteristics and clinical outcomes. METHODS AND RESULTS: Intravenous heparin was administered as a 5000-U bolus followed by an initial infusion of 1000 U/h, with dose adjustment to achieve a target aPTT of 60 to 85 seconds. aPTTs were collected 6, 12, and 24 hours after thrombolytic administration. Higher aPTT at 24 hours was strongly related to lower patient weight (P < .00001) as well as older age, female sex, and lack of cigarette smoking (all PT< .0001). At 12 hours, the aPTT associated with the lowest 30-day mortality, stroke, and bleeding rates was 50 to 70 seconds. There was an unexpected direct relationship between the aPTT and the risk of subsequent reinfarction. There was a clustering of reinfarction in the first 10 hours after discontinuation of intravenous heparin. CONCLUSIONS: Although the relationship between aPTT and clinical outcome was confounded to some degree by the influence of baseline prognostic characteristics, aPTTs higher than 70 seconds were found to be associated with higher likelihood of mortality, stroke, bleeding, and reinfarction. These findings suggest that until proven otherwise, we should consider the aPTT range of 50 to 70 seconds as optimal with intravenous heparin after thrombolytic therapy.

Adult↗
PubMed1996

Liquid secondary ion mass spectrometry of methyl glycosides of oligosaccharides using matrices containing carboxamides.

Intense cluster ions corresponding to proton-bound hetero-dimers of an amide molecule and an oligosaccharide molecule are observed in the liquid secondary ion mass spectra of methyl glycosides of oligoxylans if a solution of an aliphatic carboxamide in glycerol is used as the liquid matrix. These cluster ions are particularly abundant and persist for a long period if urea (U) or thiourea (TU) is used as the matrix additive. In these cases, cluster ions containing more than one molecule of U or TU and two oligosaccharide molecules are also observed. The intense signal due to the proton-bound hetero-dimer between U or TU and the oligosaccharide can be used with advantage for a molecular weight determination. The bonding interactions between a protonated saccharide molecule and a molecule U or TU in the proton-bound hetero-dimers are so strong that the urea molecules remain attached to the fragment ions during the decay of metastable cluster ions and even during collision-induced dissociation. Thus, the mass-analysed ion kinetic energy spectra of these proton-bound hetero-dimers are dominated by abundant cluster ions [Bn+U] and [Ym+U] arising from cleavage of the glycosidic bonds within the oligosaccharides. The collisionally-activated mass spectra of the proton-bound hetero-dimers additionally contain peaks of the free ions Bn and Ym. Therefore, these spectra clearly reflect the arrangement of the monosaccharide residues in the oligosaccharide and can be used conveniently for structural analysis.

Carbohydrate Sequence↗
PubMed1996

Sensitivity-enhanced echo-planar MRI at 1.5T using a 5 x 5 mesh dome resonator.

In this work a 5 x 5 mesh dome resonator that has been optimized for functional brain imaging is presented. The resonator was reduced in length and diameter compared with previous versions to reduce sample losses, thus enhancing the signal-to-noise ratio of the acquired data. In addition, a 5 x 5 mesh design was employed, which offered improved axial homogeneity over an earlier 3 x 3 mesh version. The new resonator exhibited high sensitivity and good homogeneity over the brain volume, permitting analysis of functional activation over large areas of the cerebral cortex. In a direct comparison with a standard clinical head-imaging resonator, the high sensitivity of the 5 x 5 mesh dome resonator resulted in greater statistical confidence in functional activation.

Cerebral Cortex↗
PubMed1996

Cytogenetic findings in 175 patients indicate that items of the Kiel classification should not be disregarded in the REAL classification of lymphoid neoplasms.

Cytogenetics have proved to be a valuable tool for classifying systemic lymphatic neoplasms, as this technique allows different stem line aberrations and clonal developments to be distinguished. This study was designed to analyze how far groups defined according to common cytogenetic features correlated with their position in either the Kiel (KC) or the REAL classification. Cytogenetic analyses were performed on material from 175 patients with lymphoid neoplasms (LN). Samples were prepared from peripheral blood and bone marrow in acute lymphoblastic leukemia (ALL), from bone marrow in multiple myeloma (MM), and from lymph node biopsies in lymphomas. The results of this study support the inclusion of ALL, MM, and extranodal lymphomas into a comprehensive classification, because their chromosomal aberrations were always characteristic for LN. From the cytogenetic point of view, a subgroup of ALL appears as a leukemic manifestation of lymphoblastic lymphoma. MM have structural aberrations of chromosomes 1, 11, and 14 and secondary aberrations of chromosomes 3, 6, 7, 12, 13, and 18, all of which are characteristic for lymphatic disease. The groups with follicle center cell lymphoma and mantle cell lymphoma correlate well with our results both in the low-grade subtype and in the blastic variant type, the majority of cases demonstrating t(14; 18) and its variants and t(11; 14), respectively. In contrast, the group of diffuse large B-cell (DLB) lymphomas proved to be heterogeneous on the basis of our cytogenetic results. Accordingly, we would suggest keeping the immunoblastic lymphoma (IB) subtype defined by the KC. IB demonstrates no stem line aberration in common with any other group and seems to be characterized by stem line aberrations involving chromosomes 3 and 6. As some DLB lymphomas have a t(14;18) or variant translocations involving chromosome 18, they should either be separated as a subgroup or included into the group of follicle center lymphomas.

Adult↗
PubMed1996

Human eating: evidence for a physiological basis using a modified paradigm.

The aim of these studies was to determine if meal requests and changes in hunger ratings in humans were related to spontaneous changes in blood glucose concentration. In our first study, 18 healthy subjects were acutely isolated from food ant time cues. Blood glucose was continuously monitored online and visual analog ratings of hunger were obtained following an overnight fast. Spoken meal requests, if they occurred, were also recorded. In 83% of the subjects, both the perception and behavioral expression of hunger, as assessed by changes in hunger ratings and meal requests, were preceded by, and correlated with, brief, transient declines in blood glucose (nadir: -10% at 27 min). The pattern, magnitude and time course of these declines was similar to those observed in rats. This significant association, between increased expression of hunger and declines in blood glucose, is being tested in a second, ongoing study using acute insulin infusions to mimic spontaneous transient declines in blood glucose. Each subject was studied twice: either insulin or saline was infused while hunger ratings were obtained. Preliminary results in five subjects indicate that hunger ratings increased after insulin-induced transient declines in blood glucose. No change in hunger ratings occurred when blood glucose concentration was stable. These results suggest that this temporal pattern of blood glucose reflects an antecedent physiological event or provides a signal related to the expression of hunger in humans. Further understanding of human eating may result from investigation of the complex interaction of physiological and other factors in an experimental setting that allows the expression the behavior under study.

Adult↗
PubMed1996

A gene correlate of geotaxis near Adh (2-50.1) in Drosophila melanogaster.

As part of a long-term study (38+ years) to identify genetic correlates of geotaxis in Drosophila melanogaster, the investigators report the results of allozyme-level analyses of 2 lines derived from hybridizing high- and low-selected lines that have evolved stable, extreme expressions of geotaxis. Allelic variation at Adh was associated with geotactic performance in 1 hybrid-derived line, but not in another, after 66 free-mating generations beyond the F2 generation. A second-chromosome gene correlate of geotaxis may lie within 1 map unit of Adh. Population genetic analyses suggest that there were different selection pressures on the hybrid-derived lines and that the fixation of PGD-A in the high-geotaxis line was probably due to a founder-effect event.

Alcohol Dehydrogenase↗
PubMed1996

A comparative study of different means of assessing long-term energy expenditure in humans.

We compared three independent techniques for measurement of total energy expenditure (TEE) in human subjects: 1) weight-maintaining energy intake (dietTEE), 2) 24-h chamber calorimetry (chamberTEE), and 3) differential elimination rates 2H2O and H(2)18O (isotopeTEE). Twenty-three healthy adult in-patients [19 never obese (NO), 2 obese (OB), and 2 formerly-obese (RO); 9 female, 14 malel] ingested a liquid formula diet (40% of calories as fat, 45% carbohydrate, 15% protein), the volume of which was adjusted until body weight was stable for at least 14 days. Body composition was then determined by hydrodensitometry, isotope dilution, and dual photon beam absorptiometry (DXA). The thermic effect of feeding (TEF) and resting energy expenditure [REE; measured before arising (dietREE) and after arising (chamberREE)] were determined by indirect calorimetry. Non-resting energy expenditure (NREE) was calculated as NREE = TEE - (REE + TEF). Subjects then gained or lost 10% of their body weight and were restudied as described above. All measures of TEE were significantly correlated (dietTEE vs. chamberTEE r2 = 0.75; dietTEE vs. isotopeTEE r2 = 0.88; isotopeTEE vs. chamberTEE r2 = 0.73; P < 0.0001). ChamberTEE (mean +/- SE = 2,107 +/- 64 kcal/day) was approximately 20% lower than either dietTEE (2,536 +/- 94 kcal/day, P < 0.0001) or isotopeTEE (2,564 +/- 83 kcal/day, P < 0.0001). When data were normalized to metabolic mass, weight gain of 10% was associated with significant increases in dietTEE (P < 0.005) and isotopeTEE (P < 0.05) but not chamberTEE; weight loss of 10% was associated with significant reductions in dietTEE (P < 0.005) and isotopeTEE (P < 0.05) but not chamberTEE. We conclude that measures of energy expenditure obtained in a highly controlled environment by caloric titration (dietTEE) or differential excretion rates of 2H2O and H(2)18O (isotopeTEE) are not significantly different and that measurements of TEE obtained in a respiratory chamber (chamberTEE) are significantly lower than dietTEE or isotopeTEE, probably largely due to limitations on physical activity in the chamber.

Adult↗
PubMed1996

Effects of gender, body composition, and menopause on plasma concentrations of leptin.

Circulating concentrations of leptin ([leptin]) vary directly with body mass index and percentage body fat, and may thus constitute an afferent limb of a system regulating body fatness. We tested the hypotheses that: 1) Plasma [leptin] vary more directly with absolute fat mass than with fractional body fatness per se: and 2). The relationship between fat mass and [leptin] is significantly affected by gender and by menopausal status. [Leptin] in the post-absorptive state was examined in 67 subjects (26 male, 20 premenopausal female, 21 postmenopausal females; 43 never-obese, 24 obese) at usual body weight. Body composition was determined by hydrodensitometry, and [leptin] was determined by a double antibody ELISA assay. In male and pre-menopausal female subjects, subcutaneous adipose tissue aspirations were performed for determination of adipocyte volume by the osmium fixation method, and a 3 hour oral glucose tolerance tests was performed. At usual body weight, ([leptin]) was better correlated with absolute fat mass than with body mass index (BMI) or percentage body fat. BMI and % body fat did not account for any of the variance in [leptin] beyond that attributable to FM, per se. The regression equations relating FM to [leptin] did not differ significantly between obese and never-obese subjects. [Leptin] and fasting serum insulin concentrations were significantly correlated in males only. [Leptin] was significantly higher in pre- and post-menopausal females compared to males, even when [leptin] was corrected for differences in body composition (pre-menopausal females > post-menopausal females > males). While plasma [leptin], corrected for FM, declines significantly in women post-menopause, this decline is not sufficient to account for the striking sexual dimorphism in the relationship of leptin to fat mass. This sexual dimorphism is apparently also due, in part, to a suppressive effect of circulating androgens on [leptin].

Adipose Tissue↗
PubMed1995

Non-involvement of the redox site of NMDA receptors in bidirectional synaptic plasticity in the CA1 area of the rat hippocampus in vitro.

We have examined the effects of the redox reagent 5,5'-dithiobis-2-nitrobenzoic acid (DTNB) on synaptic potentials recorded extracellularly from the CA1 area in hippocampal slices following low frequency stimulation (LFS) and tetanic stimulation (TS). Application of DTNB (200 microM) neither changed synaptic responses, nor prevented the expression of TS-induced long-term potentiation of synaptic responses and their depotentiation by LFS. Conversely, in naive slices, LFS still induced long-term depression of synaptic responses following application of DTNB. This depression could be subsequently reversed with a TS. It is concluded that the redox state of N-methyl-D-aspartate receptors does not affect the expression of long-term potentiation and depression of synaptic responses.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1995

Illusory contours activate specific regions in human visual cortex: evidence from functional magnetic resonance imaging.

The neural basis for perceptual grouping operations in the human visual system, including the processes which generate illusory contours, is fundamental to understanding human vision. We have employed functional magnetic resonance imaging to investigate these processes noninvasively. Images were acquired on a GE Signa 1.5T scanner equipped for echo planar imaging with an in-plane resolution of 1.5 x 1.5 mm and slice thicknesses of 3.0 or 5.0 mm. Visual stimuli included nonaligned inducers (pacmen) that created no perceptual contours, similar inducers at the corners of a Kanizsa square that created illusory contours, and a real square formed by continuous contours. Multiple contiguous axial slices were acquired during baseline, visual stimulation, and poststimulation periods. Activated regions were identified by a multistage statistical analysis of the activation for each volume element sampled and were compared across conditions. Specific brain regions were activated in extrastriate cortex when the illusory contours were perceived but not during conditions when the illusory contours were absent. These unique regions were found primarily in the right hemisphere for all four subjects and demonstrate that specific brain regions are activated during the kind of perceptual grouping operations involved in illusory contour perception.

Brain Mapping↗
PubMed1995

Changes in energy expenditure resulting from altered body weight.

BACKGROUND: No current treatment for obesity reliably sustains weight loss, perhaps because compensatory metabolic processes resist the maintenance of the altered body weight. We examined the effects of experimental perturbations of body weight on energy expenditure to determine whether they lead to metabolic changes and whether obese subjects and those who have never been obese respond similarly. METHODS: We repeatedly measured 24-hour total energy expenditure, resting and nonresting energy expenditure, and the thermic effect of feeding in 18 obese subjects and 23 subjects who had never been obese. The subjects were studied at their usual body weight and after losing 10 to 20 percent of their body weight by underfeeding or gaining 10 percent by overfeeding. RESULTS: Maintenance of a body weight at a level 10 percent or more below the initial weight was associated with a mean (+/- SD) reduction in total energy expenditure of 6 +/- 3 kcal per kilogram of fat-free mass per day in the subjects who had never been obese (P < 0.001) and 8 +/- 5 kcal per kilogram per day in the obese subjects (P < 0.001). Resting energy expenditure and nonresting energy expenditure each decreased 3 to 4 kcal per kilogram of fat-free mass per day in both groups of subjects. Maintenance of body weight at a level 10 percent above the usual weight was associated with an increase in total energy expenditure of 9 +/- 7 kcal per kilogram of fat-free mass per day in the subjects who had never been obese (P < 0.001) and 8 +/- 4 kcal per kilogram per day in the obese subjects (P < 0.001). The thermic effect of feeding and nonresting energy expenditure increased by approximately 1 to 2 and 8 to 9 kcal per kilogram of fat-free mass per day, respectively, after weight gain. These changes in energy expenditure were not related to the degree of adiposity or the sex of the subjects. CONCLUSIONS: Maintenance of a reduced or elevated body weight is associated with compensatory changes in energy expenditure, which oppose the maintenance of a body weight that is different from the usual weight. These compensatory changes may account for the poor long-term efficacy of treatments for obesity.

Adult↗
PubMed1995

The reaction of D-glucose with aminoguanidine.

The reaction of D-glucose with aminoguanidine was examined at pH 7.0 and 37 degrees C (phosphate buffer). Under these conditions, the reaction requires ca. 42 days for 50% of the sugar to react, as measured by the disappearance of D-glucose, and at 60 degrees C all the aminoguanidine had reacted within 72 h. The initial product, a beta-D-glucopyranosyl aminoguanidine (1) was obtained in the crystalline state as the trifluoroacetate salt. Data collected on this compound suggests that, in solution, it is largely a glycosylamine in the beta pyranose form. Acetylation gave a crystalline heptaacetate (2), which, in solution (as evidenced by NMR spectroscopy) exists in two different conformational forms. The crystal structure of the heptaacetate also includes two conformers. Both crystallographically independent molecules are in the normal beta pyranose form, with the acetylated guanyl residue occupying different spatial positions relative to the ring.

Carbohydrate Conformation↗
PubMed1995

K+ channels in the basolateral membrane of rat cortical collecting duct are regulated by a cGMP-dependent protein kinase.

The basolateral membrane of the rat cortical collecting duct (CCD) principal cell is K+ conductive. Recently, two different K+ channels have been described, namely a small- and an intermediate-conductance K+ channel (s-K+ and i-K+) which most likely are responsible for the macroscopic K+ conductance. K+ channel activity was investigated at the single-channel level using the patch-clamp technique. Patch-clamp recordings were obtained from enzymatically isolated CCD segments and freshly isolated CCD cells using conventional cell-free, cell-attached, cell-attached-nystatin and slow-whole-cell methods. Both K+ channels showed rundown behaviour after excision. In an excised inside-out oriented membrane, K+ channels could be activated by simultaneous addition of 0.1 mmol/l (cyclic guanosine monophosphate (cGMP) and 0.1 mmol/l MgATP to the bath. The i-K+ was activated in 13 out of 45, the s-K+ in 15 out of 45, cases. No activation of either channel was observed with cGMP alone (0.1 mmol/l), MgATP alone (0.1 mmol/l), cGMP and guanosine triphosphate (GTP) (0.1 mmol/l each) or cyclic adenosine monophosphate (cAMP) and MgATP (0.1 mmol/l each) n = 15, 11, 7, 8, respectively). The activated s-K+ could be blocked by KT 5823 (n = 8), a specific inhibitor of a cGMP-dependent protein kinase (PKG). An inhibition of the activated i-K+ was seen in seven cases. The membrane potential hyperpolarized significantly after application of dibutyryl-cGMP (0.1 mmol/l, n = 6) or nitroprusside (10 mumol/l, n = 5), which is known to liberate NO and thus increase the intracellular cGMP level.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1995

Effects of diadenosine polyphosphates, ATP and angiotensin II on membrane voltage and membrane conductances of rat mesangial cells.

Diadenosine polyphosphates have been shown to influence renal perfusion pressure. As mesangial cells may contribute to these effects we investigated the effects of diadenosine triphosphate (Ap3A), diadenosine tetraphosphate (Ap4A), diadenosine pentaphosphate (Ap5A) and diadenosine hexaphosphate (Ap6A) on membrane voltage (Vm) and membrane conductance (gm) in mesangial cells (MC) of normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats in primary and long-term culture. We applied the patch-clamp technique in the fast-whole-cell configuration to measure Vm and gm. To compare the effects of diadenosine polyphosphates with hitherto known agonists we also tested adenosine 5&acute;-triphosphate (ATP) and angiotensin II (Ang II). As there was no significant difference in the Vm values in MC of WKY (-42 +/- 1 mV, n = 70) and SHR rats (-45 +/- 2 mV, n = 99) as well as in the agonist-induced changes of Vm, all data were pooled. The Vm of all the cells was -44 +/- 1 mV (n = 169) and gm was 15.9 +/- 1.8 nS (n = 141). Ion-exchange experiments showed the presence of a K+ and a non-selective cation conductance in resting MC whereas a Cl- conductance or a Na+-selective conductance could not be observed. Ap3A, Ap4A, Ap5A, AP6A and ATP each at a concentration of 5 micromol/l, led to a significant depolarization of Vm by 5 +/- 2 mV (n = 14), 7 +/- 1 mV (n = 25), 3 +/- 1 mV (n = 23), 2 +/- 1 mV (n = 16), and 14 +/- 2 mV (n = 23), respectively. For Ap4A, the most potent diadenosine polyphosphate, we determined the half-maximally effective concentration (EC50) as 6 micromol/l (n = 5-25), for ATP as 2 micromol/l (n = 9-37), and for Ang II as 8 nmol/l (n = 6-18). Ap4A 100 micromol/l increased gm significantly by 55 +/- 20% (n = 16), 100 micromol/l ATP by 135 +/- 60% (n = 18). The diadenosine polyphosphates examined were able to depolarize Vm (Ang II > ATP > Ap4A > Ap3A > Ap5A > Ap6A) by activation of a Cl- conductance and a non-selective cation conductance, as do ATP or Ang II.

Adenosine↗
PubMed1995

The future for treatment by bone marrow transplantation for adrenoleukodystrophy, metachromatic leukodystrophy, globoid cell leukodystrophy and Hurler syndrome.

Within the past decade, bone marrow transplantation has been applied to over 200 patients worldwide with the intention of treating storage diseases. Bone marrow transplantation has provided a method for treatment of adrenoleukodystrophy, metachromatic leukodystrophy, globoid cell leukodystrophy and Hurler syndrome. After engraftment, significant improvement in the clinical course of each of these diseases occurs. Survival data of engrafted patients are superior to those of non-transplanted. Engraftment and the resulting enzymatic reconstitution are concordant. Outcomes based on neuropsychological tests indicate continued maintenance and in some cases increase in cognitive function. Magnetic resonance imaging as well as spectroscopic examinations of the brain provide further evidence that positive changes occur in the central nervous system following long-term engraftment. A better quality of life follows engraftment. Greater gains from use of bone marrow transplantation for these particular storage diseases will occur in the future. Earlier diagnosis will allow bone marrow transplantation in the presymptomatic stage at a younger age, providing an enhancement of positive effects noted from such treatment. At the same time, advances in bone marrow technology will serve to reduce the risk factors involved with the bone marrow transplantation process itself. These two factors taken together will be more than additive in providing benefits from use of bone marrow transplantation.

Adrenoleukodystrophy↗
PubMed1995

Strategies for school-based response to loss: proactive training and postvention consultation.

The suicide of a student or staff member is one of the most difficult crisis confronting a high school. This article describes the first year of a school-based postvention program to train and consult with crisis personnel in a structured response to this crisis. Responding to Loss (RTL) is one program offered by Community Action for Youth Survival, a project of the Ronald McDonald Children's Charities. Serving a contiguous three county urban area, this program integrates public health, epidemiological, psychiatric, and prevention paradigms to provide a comprehensive approach to the aftermath of adolescent suicide. RTL provides an interdisciplinary model for comprehensive, school-based postvention programs based on the guidelines developed by the Centers for Disease Control and national and local psychological autopsy data. It highlights the significance of responding to increased rates of suicide in minority youth, suicide witnessed by peers, and suicide victims who have dropped out of school. Organizational issues, such as systematic school entry, development of a computerized school database, proactive training, and collaboration with the offices of medical examiners and coroners, are described. Initial evaluation data from year 1 indicate significant gains in participants' knowledge and skills, as well as a high rate of consumer satisfaction.

Adolescent↗
PubMed1995

Analyzing correlations of three types in selected lines of Drosophila melanogaster that have evolved stable extreme geotactic performance.

The behavior-genetic analysis of Drosophila melanogaster with geotactic performance as the phenotype is an ideal model system with which to investigate the complex relations between heredity and behavior. As part of a long-term, 38-year study, we report 4 experiments that identify and analyze trait correlations in the selected high- and low-geotaxis lines. We performed F2 correlational analyses and backcrosses to examine 3 types of correlations: (a) genotype-genotype (alcohol dehydrogenase [Adh]-amylase [Amy]), (b) genotype-phenotype (Adh and Amy-geotaxis), and (c) phenotype-phenotype (mate preference-geotaxis). Only the Adh-geotaxis correlation survived meiosis and reappeared in the F2 generation, which indicates a genotype-phenotype correlation, whereas the others did not. The importance of hybrid correlational analysis to the behavior-genetic analysis of a species is discussed.

Alcohol Dehydrogenase↗