Biomedical subjects
J Hirsch
Publications and source records attributed to J Hirsch.
Genetic changes occurring over 500 generations in lines of Drosophila melanogaster selected divergently for geotaxis.
Explore the source record for details and available documents.
Reversal of genetic homeostasis in laboratory populations of Drosophila melanogaster under long-term selection for geotaxis and estimates of gene correlates: evolution of behavior-genetic systems.
Among Drosophila melanogaster, divergently selected for geotaxis intermittently over 600 generations (28 years), about 80,000 animals have been analyzed behavior-genetically. Each major chromosome pair from two lines was isogenized on an unselected isogenic background. Measurement of their behavioral effects revealed the relative magnitudes II greater than III greater than X for the negatively geotactic (high) line and X greater than III greater than II for the positively geotactic (low) line. When reversing selection for the now phenotypically stable high and low lines and then repeatedly relaxing the reversals, a new genetic homeostasis in the low line was indicated by the return of the reversed-line average scores towards the low extreme; that is, the low line has attained a stable equilibrium for positive geotaxis, an uncharacteristic behavior and an effect not seen before 1979. This change suggests the recent evolution of a new coadaptation among genes. Although not as conclusive, a similar genetic interpretation is suggested for the high line.
A fundamental distinction in the analysis and interpretation of behavior.
In 1935 the editor of this journal called attention to limitations inherent in the presentation of grouped or average data (Dunlap, 1935/1982). Because of contemporary misconceptions analogous to those Dunlap discussed, we clarify and emphasize the important distinction between the use of grouped data to demonstrate learning in a species and the reliable measurement of learning in identified individuals, as well as how best to assess the outcome of selective breeding with conditioning as the phenotype.
Abnormalities of fetal cranial contour in sonographic detection of spina bifida: evaluation of the "lemon" sign.
Previous reports have shown that visualization of the "lemon" sign on fetal cranial sonograms may indicate the presence of spina bifida before 24 weeks. To further characterize this sign and determine whether other factors might be associated with it, the authors retrospectively (n = 31) and prospectively (n = 19) evaluated 50 fetuses with spina bifida. The lemon sign was noted in 32 (64%), including 24 of 27 (89%) fetuses evaluated before 24 weeks. The presence of both ventricular dilatation, found in 41 (82%) of the fetuses, and a lemon sign correctly predicted spina bifida in all but one case. The location of the spinal defect and other anomalies were not associated with the lemon sign. The lemon sign is an important indicator of spina bifida, particularly in high-risk pregnancies, and should improve sonographic detection of spina bifida before 24 weeks.
Evaluation of corrected loss variance as a visual field index. I. CLV exceeds RMS in discriminating between glaucoma-suspect patients with no loss of visual sensitivity and normal observers.
Octopus visual fields were compared for three groups of patients: (1) diagnosed glaucoma patients; (2) glaucoma-suspect patients, and (3) control observers. Four visual field indices were analyzed for each visual field: mean sensitivity, short-term fluctuation (root mean square), mean defect, and corrected loss variance. Among the four indices, corrected loss variance was the only index that discriminated the glaucoma-suspect group from the control group, while, as expected, the glaucoma group differed from the other two study groups for all four indices. These data support the view that corrected loss variance may provide highly sensitive information on which to base an early clinical diagnosis of glaucoma in patients who do not demonstrate traditional field loss.
Evaluation of corrected loss variance as a visual field index. II. Corrected loss variance in conjunction with mean defect may identify stages of glaucoma.
Although corrected loss variance (CLV) may enhance the sensitivity of field examinations in the early stages of glaucoma, the value of CLV has not been investigated with advancing glaucoma. In this study we report mean defect (MD) and CLV for 266 Octopus field examinations (a total of 57 eyes and 47 patients with open-angle glaucoma) collected over a period of approximately 6 years on a stored database system. We find that CLV is generally elevated (relative to the normal controls) independent of MD. However, the elevated level of CLV does not vary with increasing field loss as indicated by MD. A classification system for defining stages of glaucoma is proposed utilizing CLV and MD as a combined index.
Significance of a single umbilical artery in fetuses with central nervous system malformations.
To determine whether the presence of a single umbilical artery (SUA) is useful information for evaluating fetuses with known central nervous system (CNS) malformations, the present study reviewed 107 consecutive cases of fetal CNS malformations (hydrocephalus, meningomyelocele, Dandy-Walker malformation, and holoprosencephaly) identified by prenatal sonography. Of the 107 fetuses studied, 20 (18%) had a SUA noted at the time of delivery or autopsy and 87 (81.3%) had two umbilical arteries. Of the 20 fetuses with a SUA, six were prospectively recognized on sonography, six were identified retrospectively, and eight could not be evaluated due to oligohydramnios or technical factors. All 20 fetuses with a SUA had extra-CNS anomalies and 8 of 15 (53%) fetuses tested had chromosomal abnormalities. These rates were significantly higher (P less than .05) than observed in 87 fetuses with two umbilical arteries who had extra-CNS anomalies in 35 cases (39%) and chromosomal abnormalities in 11 of 45 (24%) cases tested. We conclude that identification of a SUA in combination with a CNS anomaly should suggest the presence of additional extra-CNS anomalies and is an indication for chromosomal analysis.
Dietary fat, plasma lipoproteins, and immune function in middle-aged American men.
Dietary fat has been incriminated as a positive risk factor for the development of neoplasia in human populations. We used adipose tissue fatty acid analysis as an index of dietary fat intake to study the association between dietary fat and immune function in a group of 94 free-living American males (avg age 47 years). Immunocompetence was tested by a battery of T- and B-lymphocyte stimulation tests and also by natural killer (NK) cell activity. Correlations were sought between fatty acid composition, plasma lipids, and immune responsivity. The degree of unsaturation of the diet over a polysaturated-to-saturated fat ratio range of 0.54-1.01 had no predictable effect on the immune function. Stepwise regression analysis showed that the concentrations of plasma triglycerides and cholesterol and its subfractions did not explain any of the variance in the immune tests. Palmitic acid (16:0) was associated with 7% of the variance of the response to C. albicans and E. coli, perhaps through influencing B-cell activity. Stearic acid (18:0) was correlated negatively to concanavalin A responsivity (18% of the variance) and positively to NK activity (20% of the variance). If impaired in vitro immune function is a marker of increased risk for carcinogenesis, then our data do not support a role for dietary fat influencing in any systematic manner lymphocyte function in vitro, as reflected by proliferative response or NK activity. Further, plasma lipoproteins, in particular cholesterol levels, did not appear to affect any immune function test. It remains to be studied whether dietary fat, lipoproteins, or fat-soluble substances may influence membrane structure and function and prostaglandin formation as alternative pathways in the promotion of neoplasia.
The effect of stress level, amino acid formula, and nitrogen dose on nitrogen retention in traumatic and septic stress.
Eighty-seven patients were entered into a randomized, prospective, double-blind, six-center study to evaluate the effect of amino acid loading and a formula that was branched chain enriched (50%) on nitrogen retention in metabolic stress. The patients had varying levels of metabolic stress (0-3) after major surgery, polytrauma, or surgical sepsis. The study was isocaloric and isonitrogenous and lasted for 7 days. The patients received either a standard amino acid formula (SAA) (Travasol) or a 50% branched chain enriched formula that was equimolar, leucine, isoleucine, and valine (MAA) (Travasol + Branchamin concentrate) at a dose of 1.0-2.0 g/kg/day in a fixed ratio with 114 glucose calories per gram of nitrogen administered. The nitrogen retention was proportionate to the nitrogen (and, therefore, caloric) load in both groups. The MAA group, however, had better nitrogen retention, reached nitrogen equilibrium at a lower dose of amino acids, and had less urinary nitrogen excretion per gram of nitrogen administered. Since the groups were isonitrogenous and the calorie to nitrogen ratios were fixed, it appears that nitrogen equilibrium in surgical stress is proportionate to the amino acid load over a range of 0.05-0.4 g/kg/day of nitrogen; and that MAA are more efficient at inducing nitrogen retention and a reduction in urea excretion. These effects on nitrogen retention were more significant at level 2 stress or greater. At these higher stress levels, a dose of 2 +/- 0.2 g/kg/day of MAA seemed most efficient in promoting nitrogen retention.
Adrenergic control of adipocyte lipolysis in trauma and sepsis.
Adipocyte lipolysis and its adrenergic control were studied in vitro from normal patients and those with trauma and sepsis. The adrenergic receptors were studied in terms of their responsiveness, a measure of the postreceptor mechanism, and their sensitivity, a measure of the receptor number or affinity. With early trauma, beta-adrenergic responsiveness and receptor number were significantly decreased. This is desensitization of the beta-receptors with down regulation and indicates increased in vivo lipolysis in early injury. After 4 days these changes had returned to normal. Early sepsis resulted in a significant increase in beta- and alpha-receptor responsiveness with beta-upregulation. This indicated hypersensitivity of the adipocyte adrenergic receptors and suggests the presence of an in vivo block of the adrenergic receptors in early sepsis. This would decrease adipocyte lipolysis. After 4 days there was a decrease in beta-receptor responsiveness in the patients with sepsis, indicating that the adrenergic receptor block was no longer present and adipocyte adrenergic stimulated lipolysis was increased.
Fetal hydrocephalus: sonographic detection and clinical significance of associated anomalies.
Sixty-one cases of fetal hydrocephalus were reviewed to determine the accuracy and clinical significance of prenatal ultrasound (US) for detecting concurrent anomalies. Of 61 fetuses studied, 51 (84%) had one or more major central nervous system (CNS) malformations (38 fetuses with 39 anomalies) and/or extra-CNS anomalies (34 fetuses). Only ten (16%) fetuses had no concurrent anomaly. Anomalies of the CNS were correctly identified with US in 35 of 39 (90%) cases. Of 34 fetuses (56%) with extra-CNS anomalies, 27 had multiple anomalies. One or more extra-CNS abnormality was identified with US in 22 of the 27 (81%) fetuses with multiple anomalies but no anomalies were identified with US in the seven patients with an isolated anomaly. Fetal mortality was directly related to the presence of extra-CNS anomalies (P less than .01). Many important anomalies coexisting with fetal hydrocephalus can be identified with US. Furthermore, sonographic detection of extra-CNS malformations carries a poor prognosis and was associated with a uniformly fatal outcome in this series.
Site- and sex-related differences in adrenoreceptor status of human adipose tissue.
At equal degrees of absolute adiposity, the risk of associated morbidities such as hypertension, stroke, and ischemic heart disease is greater in individuals with predominantly abdominal as opposed to gluteal fat deposits (high waist to hip circumference ratio). We studied the in vitro status of adrenergic receptors controlling lipolysis (beta 1) and antilipolysis (alpha 2) in small fragments of adipose tissue from abdominal and gluteal sc depots of six obese women and six obese men. Lipolysis rate was measured by a double isotope technique which detects changes in the specific activity of fatty acids esterified to newly synthesized triglycerides. The lipolytic response to the beta-adrenergic agonist isoproterenol was significantly greater in abdominal compared to gluteal adipose tissue in both sexes. There was, however, no significant sex-related difference in response to isoproterenol within sites. When tissue from both sites was exposed to the mixed alpha/beta-adrenergic agonist norepinephrine there was a significantly greater lipolytic response in abdominal tissue. Within-site by sex analysis indicated no significant difference in the lipolytic response of gluteal tissue to norepinephrine, but a greater response of abdominal tissue in women. Given the apparently equal degree of beta responsiveness in abdominal tissue of both sexes, the norepinephrine data suggest that men have more abdominal alpha 2 receptor function (antilipolysis) than women. This difference may partially explain the greater tendency for men to accumulate adipose tissue in the abdominal region.
Does cone positional disorder limit resolution?
We measure the center-to-center spacings and disorder in spacings between all pairs of cones in a strip of primate retina extending from the foveal center to approximately 5.75 deg of retinal eccentricity along the temporal horizontal meridian. The strip is partitioned into windows, and the positions of the cone centers in each lattice window are digitized for analysis of lattice structure and quality. We find a nearly monotonic increase in cone spacing with eccentricity. The cone mosaic is a high-quality hexagonal lattice near the foveal center, and cone positional disorder (jitter) relative to averaging spacing increases beyond about 1.5 deg. We estimate human acuity measured through the optics of the eye over a retinal region comparable with our lattice strip by pooling the results of previous investigators. When the monkey lattice is scaled to human foveal resolution, application of the sampling theorem to average cone spacing predicts these pooled visual-acuity data from the foveal center to about 1.5 deg and overestimates visual acuity more eccentrically. Orientation reversal, a new technique developed by Coletta and Williams [J. Opt. Soc. Am. 4, 1503 (1987)] for estimating the Nyquist limit, estimates Nyquist frequencies from the foveal edge to beyond 5 deg of retinal eccentricity that agree with the cutoff frequencies predicted on the basis of our average spacing measurements. We conclude that the sampling theorem based on average spacing alone predicts the Nyquist limit from the foveal center to about 5 deg when that limit is measured by using the new aliasing technique.(ABSTRACT TRUNCATED AT 250 WORDS)
Two-dot vernier discrimination within 2.0 degrees of the foveal center.
Vernier acuity (delta v) as a function of two-dot separation (s) was measured at five retinal locations between the foveal center and 2.0 deg of eccentricity. We compare these results with average cone spacing at each of the corresponding retinal eccentricities and find that the angular dot separations at which the delta v versus s function intersects the angular cone spacing at each eccentricity remain nearly constant. Further, we define a vernier Weber fraction delta v/s and find that the average Weber fraction increases by nearly a factor of 2 from the fovea to 2.0 deg of retinal eccentricity. We suggest that both receptor factors and postreceptor factors contribute to limits of vernier acuity within 2 deg of the foveal center.
Holoprosencephaly: prenatal sonographic diagnosis.
Fourteen cases of holoprosencephaly (HP), including 10 cases of alobar HP and four cases of semilobar HP, were identified by prenatal sonography. Intracranial and extracranial findings were reviewed to determine the accuracy and spectrum of the sonographic features. All 14 cases were reliably distinguished from other causes of fetal hydrocephalus (n = 58) detected during the same period by demonstrating absence of the midline echo (falx cerebri and interhemispheric fissure), fusion of the thalami, and abnormal ventricular configuration. Four cases of semilobar HP demonstrated incomplete fusion of the thalami and partial separation of the ventricles compared with alobar HP. Eight cases demonstrated a dorsal cyst including five with alobar HP and three with semilobar HP. One case demonstrated an unusual extraaxial fluid collection surrounding the brain, thought to be from rupture of a dorsal cyst. Facial features that were identified included a proboscis (three cases), midline facial cleft (three cases), and hypotelorism (five cases). Extracranial abnormalities that were identified included polydactyly (two cases), renal dysplasia (two cases), omphalocele (one case), and fetal hydrops (one case). We conclude that fetuses with HP can exhibit a spectrum of sonographic findings and that alobar or semilobar HP is reliably distinguished from other causes of fetal hydrocephalus by distinctive intracranial findings.
Intracellular myocardial pH measured in vivo with sustained and reperfused coronary occlusion.
Intracellular pH provides an important measure of the adequacy of local tissue perfusion. The purpose of this study was to measure regional intracellular myocardial pH (impH) in the ischemic zone in vivo during experimental canine coronary occlusion, with and without coronary reperfusion. Twenty adult dogs were studied. Ten dogs underwent permanent ligation of the proximal anterior left descending coronary artery (group L), five dogs had coronary reperfusion after 1 hour of total coronary occlusion (group R), and five dogs did not undergo ligation and served as controls (group C). Intracellular myocardial pH was measured by 31phosphorus nuclear magnetic resonance spectroscopy at baseline and then at 15-minute intervals for 6 hours after coronary occlusion (or after sham occlusion in group C). Baseline impH did not differ among groups (group C, 7.22 +/- 0.12 mean +/- standard error of mean; group L, 7.17 +/- 0.07; group R, 7.22 +/- 0.09). During hour 1 of total occlusion, the impH of both groups L (6.58 +/- 0.05) and R (6.55 +/- 0.08) was significantly reduced as compared with the impH of group C (7.3 +/- 0.12; p less than 0.05). At 0 to 1, 1 to 3, and 3 to 5 hours of reperfusion, the impH of group R (7.34 +/- 0.08, 7.27 +/- 0.07, and 7.29 +/- 0.06, respectively for these times) did not differ from group C (7.26 +/- 0.11, 7.21 +/- 0.07, and 7.25 +/- 0.10). At these same times, the impH of group L (6.47 +/- 0.05, 6.57 +/- 0.04, and 6.75 +/- 0.04) was significantly reduced as compared with both groups R and C (p less than 0.05). Thus a severe, persistent regional intracellular myocardial acidosis occurs in the ischemic zone with coronary occlusion but is rapidly corrected by reperfusion within 1 hour.
Organizational structure and philosophy.
Explore the source record for details and available documents.