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Biomedical subjects

J Hirsch

Publications and source records attributed to J Hirsch.

At least 163 records · Page 9Linked to original sources

A new injection portal for brachially inserted central venous catheter. A multicenter study.

Totally implantable portal systems are widely used for long-term central venous access. A new venous portal system inserted via the brachial veins (P.A.S. Port system, Pharmacia Deltec Inc, U.S.A.) was studied in five centres. From January 1988 through May 1989 61 systems were implanted. Fifty-two patients had malignant diseases. Nine cases had non-malignant disorders. The portals were implanted subcutaneously in the fore-arm and catheterization was done percutaneously (46) or by cutdown-technique (15) under local anesthesia. Catheter tip position was controlled by fluoroscopy or x-ray. The basilic vein (49) and the cephalic vein (12) were used. The total follow-up time for all systems was 323 months. Forty-five systems were still in use at the end of the observation period, six were explanted electively at the end of infusion therapy and six systems were still functioning at the time of the patient's death (at a maximum of 14 months after implantation). Temporary armphlebitis was noticed on the first postoperative week in five patients. Two P.A.S. Port systems were explanted due to infection and one because of skin rupture at the wound. One intact system was removed as it was thought to be leaking because of needle displacement. The P.A.S. Port system is easy and safe to implant with a high success rate and a low complication rate. It is well accepted by patients and nurses. The device should be advantageous in patients unsuitable for standard venous portal systems and offers an excellent alternative system for venous access.

Adolescent↗

Protein phosphorylation in isolated human adipocytes-adrenergic control of the phosphorylation of hormone-sensitive lipase.

The effect of adrenergic agents on protein phosphorylation in human adipocytes was examined. Freshly isolated human fat cells were incubated with 32PO4 in order to label intracellular ATP, then treated with a variety of adrenergic and other pharmacologic agents. Treatment with the beta-adrenergic agonist isoproterenol led to a significant increase in phosphate content of at least five protein bands (Mr 52, 53, 63, 67, 84 kDa). The increase in phosphorylation was partially inhibited by the alpha-2 agonist clonidine. Epinephrine, a combined alpha and beta agonist, was less effective at increasing phosphate content of the proteins than was isoproterenol. Neither insulin nor the alpha-1 agonist phenylephrine had any discernible effect on the pattern of protein phosphorylation. The 84 kDa phosphorylated peptide band appears to contain hormone-sensitive lipase, a key enzyme in the lipolytic pathway which is activated by phosphorylation. These results are somewhat different than previously reported results for rat adipocytes, and represent the first report of overall pattern and adrenergic modulation of protein phosphorylation in human adipocytes.

Adipose Tissue↗

Regional changes in adrenergic receptor status during hypocaloric intake do not predict changes in adipocyte size or body shape.

The anatomic distribution of fat is related to the risk for obesity-associated morbidity. Among individuals with equal degrees of relative adiposity, those with an upper-body preponderance of fat distribution (android) have higher rates of diabetes, stroke, ischemic heart disease, and early death than those with preferential deposition of adipose tissue in lower portions of the body (hips, thighs, buttocks; gynecoid. There are well-documented anatomic site-related differences in the relative activities of the adrenergic receptors (beta 1----lipolysis; alpha 2----antilipolysis) that control lipolysis. We assessed modifications of the status of alpha 2- and beta 1-adrenergic receptor and subreceptor function in small fragments of adipose tissue obtained by needle biopsy from the gluteal and abdominal subcutaneous regions of five android, seven gynecoid, and six uniformly obese women during a period of weight maintenance (4 weeks) (T1), and after 15% weight loss on an 840 kcal/d diet (T2). Measurements of body shape and adipocyte size were made and related to changes in the metabolism of these adipocytes. The waist-to-hip ratio (WHR) was used to define these three types of regional distribution of fat in these obese subjects: android = WHR greater than 0.86; gynecoid = WHR less than or equal to 0.76; uniform = WHR greater than 0.76 less than or equal to 0.86. WHR was not significantly altered by weight loss in any of the three groups. Although significant effects of time and/or anatomic site on in vitro responses to isoproterenol, norepinephrine, clonidine, forskolin, and dibutyryl cAMP were found, these did not correlate with intra-individual changes in anthropometry or adipocyte size.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗

Calorie restriction and iopanoic acid effects on thyroid hormone metabolism.

We measured the effects of iopanoic acid on thyroid hormone metabolism in obese men during severe calorie restriction to study the nutrition regulation of thyroid hormone metabolism. Eight morbidly obese men received a weight-maintenance diet followed by 6 wk of 600 kcal/d. During underfeeding, patients received iopanoic acid or placebo for 2-wk periods in a double-blind crossover fashion. Underfeeding alone (UF) produced a 28.3% decline in the serum triiodothyronine (T3) concentration, and iopanoic acid plus underfeeding (IOP) produced a 49.5% decline in T3 concentration from baseline. Serum reverse T3 concentrations increased 289% during IOP compared with UF alone (p less than 0.001). Serum TSH concentration was unchanged by underfeeding but increased twofold during IOP treatment. Thyroid hormone kinetics demonstrated a decrease in T3 production during IOP compared with UF. These findings suggest that calorie restriction regulates T3 production by modulating only type I 5'-deiodinase activity.

Adult↗

Assessment of visual-field changes before and after focal photocoagulation for clinically significant diabetic macular edema.

Visual fields were compared before and after focal photocoagulation for eyes with nonproliferative diabetic retinopathy and clinically significant diabetic macular edema. A total of 8 eyes was tested before treatment and 6-8 weeks after treatment using static automated visual fields (Octopus). The visual-field indices, mean defect (MD) and corrected loss variance, were employed as measures of retinal sensitivity. Our results show that focal photocoagulation (CLV) generally depressed sensitivity (increased MD) in the treated central 10 degrees field, whereas in the untreated control region (10-30 degrees) sensitivity generally remained stable. However, the whole-field indices indicated that overall the fields remained stable following focal photocoagulation treatment. These results suggest that although focal treatment produces local absolute visual-field defects, the effects are small relative to the global indices.

Adult↗

Lipolytic effects on diacylglycerol accumulation in human adipose tissue in vitro.

When fragments of rat or human adipose tissue, or isolated adipocytes, are incubated with [14C]glucose in vitro, [14C]diacylglycerol accumulates rapidly: it comprises 20-50% of newly synthesized (14C-labeled) acylglycerols, compared to less than 1% diacylglycerol accumulated in the bulk lipid store in vivo. The experiments reported in this study were performed to test the possibility that agents that influence the rate of lipolysis might differentially affect the accumulation of di- and triacylglycerol in human adipose tissue, and perhaps account for the discrepancy between the early labeling and the later accumulation of diacyglycerol. Fragments of gluteal subcutaneous adipose tissue obtained from obese men and women were incubated with isoproterenol, epinephrine plus yohimbine, adenosine deaminase, or dibutyryl 3',5'-cyclic adenosine monophosphate to stimulate lipolysis. Tissue fragments were also incubated with clonidine, adenosine, or insulin to inhibit lipolysis. No agent had any effect on the rate of accumulation of newly synthesized triacylglycerol. The effects of these agents on the rate of lipolysis were negatively correlated with their effects on accumulation of newly synthesized diacylglycerol. Newly synthesized diacylglycerol may be preferentially hydrolyzed by hormone sensitive lipase. This increased susceptibility to lipolytic stimulation, compared to newly synthesized triacylglycerol, may account for the minute accumulation of diacylglycerol in adipose tissue in vivo.

Adenosine↗

Mechanism of free fatty acid re-esterification in human adipocytes in vitro.

Within adipose tissue, free fatty acids liberated by lipolysis may be re-esterified into newly synthesized triacylglycerol. We hypothesized that re-esterification may occur via an extracellular route, such that free fatty acids arising from lipolysis must leave the adipocyte and be taken up again before they can be re-esterified. We simultaneously measured rates of lipolysis, acylglycerol synthesis, and free fatty acid re-esterification in human adipose tissue and isolated adipocytes in vitro, utilizing a dual-isotopic technique. We manipulated incubations to increase mixing of released free fatty acids with the incubation medium. Such manipulations should decrease the probability that released free fatty acids would be taken up and re-esterified. We found that re-esterification was decreased in isolated adipocytes compared to fragments of tissue, in shaken compared to unshaken incubations, and in low adipocyte concentrations compared to high adipocyte concentrations. Rates of acylglycerol synthesis and lipolysis were unaltered by these manipulations, indicating that changes in free fatty acid re-esterification are not secondary to effects on these processes. The results are consistent with an extracellular route for free fatty acid re-esterification. Such a mechanism suggests that adipose tissue blood flow may play an important role in the regulation of free fatty acid release from adipose tissue.

Adipose Tissue↗

Macrosomia in the postdate pregnancy: is routine ultrasonographic screening indicated?

Macrosomia is a potential but often overlooked consequence of the postdate pregnancy. A total of 317 consecutive patients with well-dated pregnancies who were seen because of fetal surveillance at greater than 41 weeks' gestation had an estimation of the fetal weight based on femur length and abdominal circumference at the initial visit. The incidence of macrosomia at 41 weeks' gestation was 25.5%. There was a higher incidence of cesarean section because of arrest and protraction disorders in the postdate pregnancies in which the infant was macrosomic (22%) versus those in which the infant was not macrosomic (10%, p less than 0.01). In a control group of 100 consecutive women delivered between 38 and 40 weeks' gestation, the incidence of macrosomia was 4%, significantly lower than the rate in the postdate patients (p less than 0.01). Incidence of cesarean section because of arrest and protraction disorders was significantly lower in this group (6%, p less than 0.05). The sensitivity and specificity of an estimated fetal weight greater than 4000 gm to predict a birth weight greater than 4000 gm were 60.5% and 90.7%, respectively, with a positive predictive value of 70% and a negative predictive value of 87%. We conclude that routine ultrasonographic screening for macrosomia may be a valuable adjunct to current fetal surveillance protocols used in the postdate pregnancy.

Cesarean Section↗

The spatial resolution capacity of human foveal retina.

An image on the retina of a human eye enters the visual system through an array of photoreceptors that sets the boundaries on the spatial detail available for neural representation. In order to investigate the extent to which the input spatial detail is preserved by the human neural system, we compare the anatomical spatial limits as determined by the Nyquist frequency, the highest spatial frequency reconstructable from the cone array, and measures of human acuity, the minimum angle resolvable. We find that the anatomical Nyquist limits determined along the temporal horizontal meridian of a well-studied human retina (Curcio, Sloan, Packer, Hendrickson & Kalina, 1987b) offer a reasonable prediction of human acuity within the retinal region extending from slightly off the exact foveal center to about 2.0 deg of retinal eccentricity. However, we find a narrow peak of anatomical resolution at the foveal center where the acuity appears to be overestimated by cone spacing.

Adult↗

The fat cell.

Investigations of how fat cells develop, store, and release energy, and what role they play in energy metabolism are presented. The importance of adipose tissue in the pathogenesis of obesity is considered.

Adipose Tissue↗

Comparison of human and monkey retinal photoreceptor sampling mosaics.

We test the hypothesis that the diameters of foveal and near-foveal rods and cones for one well-studied human photoreceptor mosaic and one well-studied monkey photoreceptor mosaic (Macaca fascicularis) are scaled relative to focal length. We conclude that this hypothesis is not supported. Rather than being scaled proportionally, the sizes of the rods and cones, respectively, are nearly equivalent for both the human and monkey resulting in an effectively finer retinal grain for the larger human eye. Furthermore, the human rod density exceeds the monkey rod density beyond about 1 deg of retinal eccentricity. These results suggest that variation across primate species is reflected in retinal sampling strategies.

Adult↗

Evidence that the glucose transporter serves as a water channel in J774 macrophages.

Water transport across plasma membranes is a universal property of cells, but the route of such transport is unclear. In this study, volume changes of cells of the J774 murine macrophage-like cell line were monitored by recording the intensity of light scattered by the cells. We investigated the effects of several inhibitors of glucose transport on cell membrane osmotic water permeability as calculated from the rates of cell volume change. Cytochalasin B (2.5 micrograms/ml), phloretin (20 microM), and tomatine (3 microM) reversibly blocked glucose uptake into these cells. All three inhibitors reversibly decreased the osmotic water permeability of J774 cells from 89.6 +/- 3.2 to 27.2 +/- 1.4 microns/sec. We conclude that a major component of the osmotic water flow across the plasma membranes of these cells is accounted for by water traversing their glucose transporters.

3-O-Methylglucose↗

Effects of rapid glucose infusion on in vivo and in vitro free fatty acid re-esterification by adipose tissue of fasted obese subjects.

Adipose tissue lipolysis and fatty acid re-esterification were examined simultaneously in vivo and in vitro in fasted human subjects receiving a constant intravenous infusion of 14C palmitate and large intravenous infusions of glucose and insulin. Under these circumstances, the plasma [FFA] declines rapidly while the specific activity of plasma FFA increases. Plasma [glycerol] remains stable or declines slowly. These in vivo changes in FFA and glycerol metabolism appear to reflect increased adipose tissue re-esterification of FFA, without an attendant decline in rate of lipolysis. However, in vitro rates of re-esterification in gluteal adipose tissue did not change sufficiently to account for the in vivo phenomena. We conclude that: (1) re-esterification in adipose tissue is an important mechanism for the decline in [FFA] induced by glucose infusion in fasted man, but in vitro studies of adipose tissue from a gluteal site do not explain the changes in plasma free fatty acid levels; (2) our data suggest that control of the net mixture of metabolic fuels leaving the adipocyte may be under the influence of pericellular blood flow in addition to ambient humoral factors or intrinsic characteristics of the adipocyte.

Adult↗