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Biomedical subjects

J Hirsch

Publications and source records attributed to J Hirsch.

At least 199 records · Page 11Linked to original sources

A macrophage defect in women with recurrent Candida vaginitis and its reversal in vitro by prostaglandin inhibitors.

The possible involvement of a defect in cellular immunity in the etiology of recurrent vaginal candidiasis was explored. The mean and range of in vitro lymphocyte proliferative responses induced by mitogens were comparable in 65 patients and 36 control subjects. In contrast, Candida-directed proliferation was reduced at least 70% below the mean control value in 73% of the patients. Further analyses on selected patients demonstrated that lymphocytes of the patients responded in the normal range to Candida if incubated in the presence of control macrophages. Conversely, macrophages of patients inhibited the responses of control lymphocytes to Candida. These effects were independent of mixed leukocyte reactions between allogeneic cells. Addition of the prostaglandin inhibitors ibuprofen and indomethacin prevented macrophages of patients from inhibiting patient or control lymphocyte proliferation. In response to Candida, macrophages from some women with recurrent vaginitis produce prostaglandin, which blocks the lymphocyte proliferation response to this organism.

Candidiasis, Vulvovaginal↗

Biometrical and chromosome analyses of lines of Drosophila melanogaster selected for central excitation.

Lines of Drosophila melanogaster, bidirectionally selected for extreme and opposite expression of central excitatory state (CES), were subjected first to biometrical and then to chromosome analysis. The analyses revealed that low CES expression is partially dominant to high, at least two chromosomes (II and III) are correlated with CES expression, for the low line, both chromosomes, II and III, are necessary for low expression, cytoplasmic factors are involved with CES expression, and loci of minor effect on the X and Y chromosomes are correlated with CES expression.

Animals↗

The relationship of dietary fat to plasma lipid levels as studied by factor analysis of adipose tissue fatty acid composition in a free-living population of middle-aged American men.

We have used adipose tissue biopsies to assess the quality of fat in the diet and its influence on plasma lipid levels in 413 free-living normolipidemic male subjects. Factor analysis identified three factors which separated the fatty acids on the basis of their chemical structure. F1--monounsaturates--animal fats; F2--saturates--carbohydrates; F3--polyunsaturates--vegetable oils. An increase in F1 was associated with an increase in plasma triglycerides (TG), plasma total cholesterol (TC), and VLDL-C: an increase in F2 led to a decrease in VLDL-C. A rise in F3 was associated with lowered TG, VLDL-C, and HDL-C but increased LDL-C. However, the contribution of each of these factors to the variance in TG, TC, LDL-C, and HDL-C was small, namely: 5.48, 1.30, 2.57, and 2.02%, respectively. A special relationship between F3 and VLDL-C was found such that 16.22% of its variance could be attributed to F3. Our conclusion is that adipose tissue composition and, by implication, the type of dietary fat intake, explains only a small proportion (1-19%) of the variance in plasma lipids in normolipidemic subjects.

Adipose Tissue↗

Does dietary linolenic acid influence blood pressure?

Short-term intervention studies have shown that diets rich in polyunsaturated fats have hypotensive properties. We have studied the long-term effects of dietary fat on blood pressure (BP) using adipose-tissue, fatty acid composition analysis in 399 free-living male subjects (average age, 47 yr). Stepwise-regression analysis showed that adipose linoleic acid (18:2 n-6) was not associated with BP, whereas an absolute 1% increase in linolenic acid (18:3 n-3) was associated with a decrease of 5 mm Hg in the systolic, diastolic, and composite mean arterial BP. Linolenic acid (18:3) comprised only one-eighth the amount of linoleic acid (18:2)--the major polyunsaturate in adipose tissue and hence in the diet (2% vs 16%)--and yet it had a disproportionate association with BP. This may be related to its role as a precursor for the production of prostaglandins and/or other vasoregulators. Dietary manipulation with n-3 fatty acids may be helpful in the treatment and prevention of hypertension.

Adipose Tissue↗

Limb-body wall complex: in utero sonographic diagnosis of a complicated fetal malformation.

Limb-Body Wall Complex is a complicated fetal malformation with the essential features of neural-tube defects, body-wall disruption, and limb abnormalities. This complex should be distinguished from other body-wall defects including omphalocele and gastroschisis since the prognosis for limb-body wall complex is uniformly poor. For 13 cases of this unusual fetal anomaly, sonographic, radiologic, and pathologic findings were correlated. Thoracic or abdominal body-wall defects, neural-tube abnormalities, severe scoliosis, positional deformities, and abnormalities of fetal membranes were consistently demonstrated on in utero sonograms. Results show that the diagnosis of limb-body wall complex can be made by prenatal sonography.

Abdominal Muscles↗

Excitatory conditioning of individual Drosophila melanogaster.

Testing individual animals from a heterogenic population of Drosophila melanogaster, we demonstrate conditioning of the proboscis extension reflex. The presentation of paired (conditioning) stimuli produced (a) an increase in the average number of conditioned responses over trials, (b) measured differences in performance levels among individual subjects, and (c) a sex difference, with more males conditioned than females, and those that did did so more quickly. The presentation of unpaired (control) stimuli produced significantly lower average levels of acquisition responding and a change in the distribution of individual response patterns. Neither central excitatory state nor sensitization induced by the conditioned or unconditioned stimuli directly affected the conditioned response, whereas unconditioned stimulus preexposure adversely affected performance levels. Presenting the unpaired (extinction) stimuli after conditioning produced less of a decline in responding than did an extinction procedure with removal of the unconditioned stimulus. With the ability to identify individual differences in acquisition and extinction patterns, and given the relatively large number of individuals that can be tested simultaneously on the automated stimulation apparatus, it is now possible to make precise behavioral measurements on samples large enough for the behavior-genetic analysis of D. melanogaster with conditioning as the phenotype.

Animals↗

The role of dietary fat in human obesity.

Both the amount and quality of dietary fat have been implicated in the pathogenesis of obesity. Adipose tissue fatty and composition, which is known to reflect dietary intake, was sampled in 413 free-living, healthy American males appearing for a routine medical examination. The average age was 46.8 +/- 11.4 years (mean +/- s.d.) and body mass index (BMI)--weight/height--was 25.2 +/- 3.4. The BMI was correlated (P less than 0.01) with known risk factors for cardiovascular disease as follows: total cholesterol (TC) r = 0.18, triglycerides (TG) r = 0.32, low-density lipoprotein cholesterol (LDL-C) r = 0.18, high-density lipoprotein cholesterol (HDL-C) r = -0.24, systolic and diastolic blood pressure (BP) r = 0.30. Underlying patterns which might be related to diet were sought in the distribution of the seven major fatty acids in adipose tissue. Statistical analysis permitted delineation of three factors which were hypothetically related to animals fat intake (F1--monounsaturates), carbohydrate intake (F2--saturates) and vegetable oil intake (F3--polyunsaturates). F1 and F3 together accounted for 12 percent of the variance in BMI while F2 had no influence. Our conclusions are that the variance in BMI is related much more to non-dietary factors than to adipose tissue fatty acid composition and that the nature of dietary fat was not a major distinguishing factor in obesity in this population. There was also no evidence for a high dietary carbohydrate (low fat) intake in the obese.

Adipose Tissue↗

Technetium-99m-labeled lymphocytes: a radiotoxicity study.

Radiolabeled white blood cells offer a unique clinical diagnostic technique. However, radiotoxicity to these radiosensitive cells must be carefully considered. Indium-111 has been shown to produce significant chromosomal alteration even at subscintigraphic doses. It has been suggested that 99mTc is less radiotoxic and may be desirable even though labeling is less efficient. The radiotoxicity of bound 99mTc was investigated in human lymphocytes by determination of division delay and chromosomal aberration as a function of increasing 99mTc activity concentration. This data revealed that human lymphocytes demonstrate significant division delay above 0.580 mCi/10(7) cells with chromosomal damage equivalent to 1 Gy of 250 keV x-ray at this level.

Cell Division↗

Imipenem/cilastatin in the treatment of obstetric and gynecologic infections.

Fifty-five patients with soft tissue pelvic infections were treated with imipenem/cilastatin 500 mg intravenously every six hours for a minimum of four days. Six patients were unevaluable, one because of protocol non-compliance and five because no pathogen was isolated. At enrollment, mean temperature was 39.5 degrees C and the mean white blood cell count was 14,700. Of 49 evaluable patients, 43 (87.8 percent) had complete clinical cures. In three of the six patients with clinical failures, subsequent alternative antibiotic treatment also failed and they required operative intervention for pelvic abscess. In two of the patients with failures, antibiotic-associated pseudomembranous colitis developed after three days of imipenem/cilastatin therapy, requiring discontinuation of the medication. At the time of discontinuation, both patients had clinical failures. All microbiologic isolates were susceptible to imipenem/cilastatin, although at least one pathogenic organism persisted in two patients with clinical failures despite apparent in vitro susceptibility of the organism to imipenem/cilastatin. Imipenem/cilastatin is a promising agent for the empiric treatment of serious obstetric and gynecologic infections although surgery often remains a necessary treatment for pelvic abscess regardless of initial antibiotic choice.

Adolescent↗

Behavioral assessment of lines of Drosophila melanogaster selected for central excitation.

Selected lines of Drosophila melanogaster, bred for high and low levels of central excitatory state (CES), were used in experiments to assess the effects of artificial selection on CES expression and to identify other correlated traits that may have become manifest during selection. Results indicate that the selected lines display (a) different levels of CES, (b) differences in water responsiveness (possibly due to differences in dehydration rates), (c) no water-induced CES, and (d) no significant amounts of sensitization or conditioning. Also, CES in the high line is not dissipated by subsequent posttest stimulations. Comparing the characteristics of CES in Drosophila and in Phormia regina reveals significant species differences. The relevance to earlier P. regina work with respect to CES and conditioning is discussed.

Animals↗

Alterations in adipocyte free fatty acid re-esterification associated with obesity and weight reduction in man.

Using a newly developed in vitro technique, the rate of re-esterification of lipolyzed free fatty acids (FFA) in small fragments of human subcutaneous adipose tissue was measured. When related to simultaneous glycerol release, this measure permits the calculation of the molar ratios of glycerol and FFA leaving the adipocyte. In weight-stable, never-obese control subjects the molar ratio of FFA:glycerol leaving the adipocytes is 1.4:1. During fasting, this ratio climbs to 2.7:1, close to the theoretical maximum of 3.0:1. Adipocytes from weight-stable obese subjects do not differ significantly from adipocytes of control in regard to this ratio. However, the adipocytes of weight-stable reduced-obese (RO) subjects display a significantly higher FFA:glycerol ratio than the adipocytes of either control or obese subjects. The presence of this fasting-like physiology in adipose tissue from weight-stable RO subjects is of particular interest since these same individuals have other systemic metabolic and subjective findings compatible with caloric deprivation.

Adipose Tissue↗

A radioisotopic technique for analysis of free fatty acid reesterification in human adipose tissue.

Reesterification rates of free fatty acids (FFA) formed by intracellular triglyceride hydrolysis in small fragments of human adipose tissue were measured. Subcutaneous gluteal adipose tissue, obtained by needle biopsy, was incubated in a buffered albumin medium containing [3H]palmitate and [14C]glucose, each of high specific activity. In triglycerides (TG) and diglycerides (DG) synthesized by the tissue, [14C]glucose is incorporated exclusively into the glyceride-glycerol moiety, and 3H appears solely in the esterified fatty acids. Since rates of TG and DG synthesis can be determined from 14C accumulation rates in these molecules, the total amounts of FFA esterified can also be calculated. The difference between this estimate of total FFA esterification and the moles of [3H]palmitate esterified to these molecules represents the amount of unlabeled FFA from ongoing TG hydrolysis that was reesterified during the incubation. FFA recycling by the reesterification pathway is an important mechanism for the control of the quantity and proportions of FFA and glycerol leaving the human adipocyte. Fasting and beta-adrenergic stimulation reduce the fraction of endogenously released FFA that are reesterified from resting values of 30-40% to 8-21%, thereby increasing the molar ratio of FFA to glycerol leaving the adipocyte. The technique described can be employed to monitor sequential changes in this important metabolic cycle in humans under a wide range of nutritional and clinical circumstances.

Adipose Tissue↗

Intraocular pressure in uremic patients on chronic hemodialysis.

Intraocular pressure (IOP) was measured before and after hemodialysis in 30 uremic patients receiving regular treatment. Osmolality, blood pressure and weight before and after dialysis were also determined. Low IOP of 11.4 +/- 2.7 and 11.5 +/- 3.1 mm Hg was found in the left and right eye, respectively. Following hemodialysis osmolality, blood pressure and body weight decreased significantly but IOP did not rise significantly. This study suggests that there is only a remote possibility for severe IOP increase following hemodialysis in uremic patients on chronic treatment.

Adolescent↗

Spatial-frequency discrimination at low frequencies: evidence for position quantization by receptive fields.

In a recent study of spatial-frequency discrimination [J. Opt. Soc. Am. 72, 1367 (1982)], we reported evidence for the quantization of position in the human visual system with the fundamental unit of quantization being the photoreceptor spacing for spatial frequencies greater than 2 cycles per degree (c/deg). In this paper we extend our measurements to lower spatial frequencies, between 0.3 and 2, which we call the mid-spatial-frequency band, and find that this band of spatial frequencies shows similar evidence for spatial quantization. However, the spacing of the fundamental unit is about 0.056 deg or approximately seven or eight times the spacing of the foveal photoreceptor instead of about 0.008 deg or approximately equal to the spacing of foveal cones. We interpret this as evidence for a class of retinal receptive fields that we call spatial-sampling fields that perform a dual function of neural blurring and spatial sampling. We propose a scaled lattice model of spatial vision that allows apparently scale-free spatial processing while retaining the advantages of linear maps. The model generalizes the notion of hyperacuity to low-resolution tasks for which neural interpolation occurs not only on the photoreceptor sampling lattice to achieve hyperacuity but also on receptive-field sampling lattices to achieve lower resolutions.

Discrimination, Psychological↗