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Biomedical subjects

A Peretz

Publications and source records attributed to A Peretz.

At least 55 records · Page 3Linked to original sources
PubMed1994

The light response of Drosophila photoreceptors is accompanied by an increase in cellular calcium: effects of specific mutations.

Photoreceptors of dissociated Drosophila retinae were loaded with the fluorescent Ca2+ indicators, fluo-3 and Calcium Green-5N. In fluo-3-loaded, wild-type photoreceptors, a rapid increase in fluorescence (Ca2+ signal) accompanied the light-evoked inward current. Removal of extracellular Ca2+ greatly reduced the Ca2+ signal, indicating Ca2+ influx as its major cause. In Calcium Green-5N-loaded trp mutants, which lack a large fraction of the Ca2+ permeability underlying the light-evoked inward current, the Ca2+ signal was smaller relative to wild-type photoreceptors. Fluo-3-loaded norpA mutant photoreceptors, which lack a light-activated phospholipase C, generated no light-evoked inward current and no Ca2+ signal. The phosphoinositide pathway therefore appears necessary for both excitation and changes in cytosolic free Ca2+ concentration.

Aniline Compounds↗
PubMed1994

Genetic dissection of light-induced Ca2+ influx into Drosophila photoreceptors.

Invertebrate photoreceptors use the inositol-lipid signaling cascade for phototransduction. A useful approach to dissect this pathway and its regulation has been provided by the isolation of Drosophila visual mutants. We measured extracellular changes of Ca2+ [delta Ca2+]o in Drosophila retina using Ca(2+)-selective microelectrodes in both the transient receptor potential (trp) mutant, in which the calcium permeability of the light-sensitive channels is greatly diminished and in the inactivation-but-no-afterpotential C (inaC) mutant which lacks photoreceptor-specific protein kinase C (PKC). Illumination induced a decrease in extracellular [Ca2+] with kinetics and magnitude that changed with light intensity. Compared to wild-type, the light-induced decrease in [Ca2+]o (the Ca2+ signal) was diminished in trp but significantly enhanced in inaC. The enhanced Ca2+ signal was diminished in the double mutant inaC;trp indicating that the effect of the trp mutation overrides the enhancement observed in the absence of eye-PKC. We suggest that the decrease in [Ca2+]o reflects light-induced Ca2+ influx into the photoreceptors and that the trp mutation blocks a large fraction of this Ca2+ influx, while the absence of eye specific PKC leads to enhancement of light-induced Ca2+ influx. This suggestion was supported by Ca2+ measurements in isolated ommatidia loaded with the fluorescent Ca2+ indicator, Ca Green-5N, which indicated an approximately threefold larger light-induced increase in cellular Ca2+ in inaC relative to WT. Our observations are consistent with the hypothesis that TRP is a light activated Ca2+ channel and that the increased Ca2+ influx observed in the absence of PKC is mediated mainly via the TRP channel.

Animals↗
PubMed1994

Effects of zinc supplementation on the phagocytic functions of polymorphonuclears in patients with inflammatory rheumatic diseases.

The phagocytosis of blood polymorphonuclear cells (PMNs) was measured by cytofluorometry in 22 patients with inflammatory rheumatic diseases before and after a 60-day treatment with 45 mg zinc daily or a placebo, and the values were compared with those obtained in a group of healthy subjects. Plasma zinc was lower than controls before supplementation and phagocytosis assessed by the percentage of PMNs exhibiting phagocytic activity was significantly impaired. Zinc supplementation increased the percentage of phagocytic PMNs and the mean phagocytic activity, particularly in subjects with initial low phagocytosis. The impairment of PMN phagocytosis could therefore be corrected by zinc supplementation, but the clinical consequence of this stimulant effect remains unknown.

Administration, Oral↗
PubMed1993

Ca2+ limits the development of the light response in Drosophila photoreceptors.

The development of the light response was followed in Drosophila photoreceptors at 25 degrees C. In whole-cell recordings from dissociated ommatidia, responses to light were first detected at 82 h post-puparium formation; over the next 8 h sensitivity to light increased exponentially by 5 or 6 orders of magnitude. The end of this phase coincided with the maturation of the rhabdomere as measured by whole-cell capacitance. There was a modest 5-10fold further increase in sensitivity over the final 10 h of pupal development (90-100 h). During a narrow developmental time window (82-87 h) no responses could be detected using non-invasive recording techniques (electroretinogram or suction electrode), and responses to light could only be elicited in whole-cell recordings when micromolar concentrations of Ca2+ are included in the pipette. It seems unlikely that cytosolic Ca2+ per se is the limiting factor, and we suggest instead that the failure to respond to light is due to the lack of Ca2+ in the InsP3-sensitive intracellular stores and that the presence of Ca2+ in these stores is an absolute requirement for phototransduction in Drosophila.

Animals↗
PubMed1993

Protein kinase C is required for light adaptation in Drosophila photoreceptors.

Protein kinase C (PKC) is a key enzyme for many cellular processes but its physiological roles are poorly understood. An excellent opportunity to investigate the function of PKC has been provided by the identification of an eye-specific PKC in Drosophila and a null PKC mutant, inaCP209 (refs 5,6). Bright conditioning lights delivered to inaC photoreceptors lead to an abnormal loss of sensitivity in whole cell recordings from dissociated ommatidia; this has been interpreted as 'hyper-adaptation' and PKC's role has been suggested to be distinct from light adaptation. A presumably related finding is that during intense light, the response of inaC declines to baseline. Invertebrate photoreceptors use the phosphoinositide signalling cascade, responding to single photons with so-called quantum bumps which sum to form the macroscopic response to light. Light adaptation allows photoreceptors to adjust their sensitivity over the enormous range of ambient intensities. Although the molecular mechanism of light adaptation remains obscure, it is a negative-feedback process mediated by a rise in cytosolic calcium and a decrease in bump size. We now show that under physiological conditions light adaptation is severely reduced in inaC, suggesting that eye-specific PKC, itself activated by a rise in cytosolic calcium and diacylglycerol, is required for adaptation. Furthermore, we show that in the absence of PKC individual bumps fail to terminate normally, an effect that can account for the pleiotropic manifestations of the inaC phenotype.

Adaptation, Ocular↗
PubMed1993

Decrease of bone mineral density during estrogen substitution therapy.

A decrease in bone mineral density (BMD) in patients treated with hormone replacement therapy (HRT) is sometimes observed in clinical practice. In order to assess the frequency and the characteristics of these cases, we reviewed the data of 102 women treated with HRT for more than 2 years, and who had undergone at least 3 lumbar BMD measurements during that period. For each patient, a linear function was fitted to the BMD data in relation to time. The slope was calculated. There was an overall gain in BMD during treatment, mean (+/- S.E.M.) values of slope 0.007 g/cm2/year (+/- 0.002). Fifty-three patients had a slope higher than 0.005, 28 a slope close to 0 (between 0.005 and -0.005) and 21 a slope lower than -0.005. By dividing the patients in tertiles of slopes (tertile I: slope < 0; tertile II: 0 < slope < 0.011; tertile III: slope > 0.011), significant differences were observed between the three groups of slope for the initial BMD (P < 0.001), hydroxyproline/creatinine ratio (P < 0.01), weight, DHEAS and alkaline phosphatase (P < 0.05). Only 1 of the 15 patients with a low bone mass (lower than mean +/- 1 S.D.) had a negative slope, while 9 of the 16 with a high-bone mass (higher than mean +/- 1 S.D.), had a negative slope. Under HRT, about 21% of postmenopausal women have a slight decrease in BMD as assessed by DPA. Because of the DPA coefficient of variation, however, the exact number of bone losers cannot be determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗
PubMed1993

Zinc distribution in blood components, inflammatory status, and clinical indexes of disease activity during zinc supplementation in inflammatory rheumatic diseases.

The effects of zinc supplementation on zinc status and on clinical and biological indicators of inflammation were investigated in 18 patients with chronic inflammatory rheumatic diseases and in 9 healthy control subjects. Patients with mild and recent onset disease were assigned to a 60-d trial to receive either 45 mg Zn (as gluconate)/d or a placebo, while control subjects received the zinc supplement. Baseline mean plasma zinc of the patients was low whereas mononuclear cell zinc content was elevated, suggesting a redistribution of the element related to the inflammatory process rather than to a zinc-deficient state. Zinc supplementation increased plasma zinc to a similar extent in patients and in control subjects, which suggested no impairment of zinc intestinal absorption as a result of the inflammatory process. On the contrary, erythrocyte and leukocyte zinc concentrations were not modified in the two groups examined. No beneficial effect of zinc treatment could be demonstrated on either clinical or inflammation indexes.

Adult↗
PubMed1993

Bone mineral density measured by dual photon and dual energy X-ray absorptiometry: a problem of accuracy.

Dual photon absorptiometers (DPA) are currently being replaced by dual energy X-ray absorptiometers (DXA) for measurements of bone mineral density (BMD). In order to evaluate how to use the previously obtained BMD results by DPA (BMDo) in the follow-up of patients, the following study was performed. Ninety-five women who had had BMDo during the last 12 months were selected. L2-L4 BMD was measured twice on the same day using both DPA (BMDp) and by DXA (BMDx). BMDp was highly correlated to BMDx (R = 0.95; P < 0.001) but a wide variation of the ratio BMDp:BMDx was observed which ranged between 0.65 and 1.09 (mean 0.90, S.D. 0.05). There was no significant relationship between the ratio BDMp:BMDx and age or height but there was a significant relationship between this ratio and the weight of the patient (R = 0.31; P < 0.001). The results also indicated that the correlation between DXA and DPA was lower than that observed between the two DPA measurements (R = 0.98; P < 0.001) which, moreover, were not performed on the same day. These observations contrast with the relatively high precision of both instruments and have to be attributed to relative inaccuracy of one or probably both techniques.

Absorptiometry, Photon↗
PubMed1993

[Osteocalcin, marker of bone metabolism].

The recent development of biochemical markers gives the opportunity to assess bone metabolism. Osteocalcin is a non collagenous protein of the bone matrix specifically synthesized by osteoblasts. The concentration of osteocalcin in serum reflects osteoblastic function and bone turnover. It has emerged as a more specific index of bone metabolism than serum alkaline phosphatase activity. Great care must be taken in blood sampling, processing and storage to avoid protein degradation. Inasmuch, we have shown in human clinical settings, the interest of this marker in patients with bone metabolic disorders characterized by increased bone turnover such as primary and secondary hyperparathyroidism or postmenopausal osteoporosis. Conversely, exogenous or endogenous high levels of corticosteroids rapidly induced a reversible decrease in osteocalcin levels.

Adrenal Cortex Hormones↗
PubMed1993

Optimized steps in fluorometric determination of thiobarbituric acid-reactive substances in serum: importance of extraction pH and influence of sample preservation and storage.

A simple, reliable, and reproducible fluorometric method for measuring thiobarbituric acid-reactive substances (TBARS) in serum is proposed, based on the reaction between malondialdehyde (MDA) and thiobarbituric acid. Formation of TBARS was complete at pH 2.4-2.6, but extraction with n-butanol proved complete only at lower pH, i.e., 1.6-1.7. Analytical recoveries of MDA added to serum were 94%-101%; within- and between-run CVs were 2.4-3.6% and 4.6-5.5%; and the detection limit for TBARS in serum was 0.10 mumol/L. Optimized conditions included: (a) collection of either serum or heparinized plasma, (b) preservation from in vitro autoxidation by glutathione and EDTA, and (c) storage at -20 degrees C up to 35 days. The mean (+/- SD) TBARS concentration in 47 healthy adults was 1.01 (0.21) mumol/L; no sex-related difference was observed. Higher concentrations were measured in patients with renal insufficiency undergoing hemodialysis and in patients with insulin-dependent diabetes, chronic pancreatitis, or liver cirrhosis.

1-Butanol↗
PubMed1992

Calcium channel blockers inhibit retinal degeneration in the retinal-degeneration-B mutant of Drosophila.

Light accelerates degeneration of photoreceptor cells of the retinal degeneration B (rdgB) mutant of Drosophila. During early stages of degeneration, light stimuli evoke spikes from photoreceptors of the mutant fly; no spikes can be recorded from photoreceptors of the wild-type fly. Production of spike potentials from mutant photoreceptors was blocked by diltiazem, verapamil hydrochloride, and cadmium. Little, if any, effect of the (-)-cis isomer or (+)-cis isomer of diltiazem on the light response was seen. Further, the (+)-cis isomer was approximately 50 times more effective than the (-)-cis isomer in blocking the Ca2+ spikes, indicating that diltiazem action on the rdgB eye is mediated by means of blocking voltage-sensitive Ca2+ channels, rather than by blocking the light-sensitive channels. Application of the Ca(2+)-channel blockers (+)-cis-diltiazem and verapamil hydrochloride to the eyes of rdgB flies over a 7-day period largely inhibited light-dependent degeneration of the photoreceptor cells. Pulse labeling with [32P]phosphate showed much greater incorporation into eye proteins of [32P]phosphate in rdgB flies than in wild-type flies. Retarding the light-induced photoreceptor degeneration in the mutant by Ca(2+)-channel blockers, thus, suggests that toxic increase in intracellular Ca2+ by means of voltage-gated Ca2+ channels, possibly secondary to excessive phosphorylation, leads to photoreceptor degeneration in the rdgB mutant.

Action Potentials↗
PubMed1992

Risk of osteoporosis in men with chronic bronchitis.

Theoretically, patients with chronic bronchitis are at risk for osteoporosis. Bone metabolism was assessed in 44 male chronic bronchitics treated with oral prednisolone (C+; n = 19) or with bronchodilatory drugs alone (C-; n = 25). In both groups, serum osteocalcin was lower (p less than 0.001) than in age- and sex-matched controls (mean (ng/ml) C+ 1.0, C- 1.9, controls 4.2), while testosterone was at the lower limit of the reference range. Low trabecular bone mineral density (BMD) was noted in the C- group (median Z score -1.0), but both cortical and trabecular BMD were depressed in the C+ group (-1.0 and -1.4, respectively). In conclusion, chronic bronchitics treated with corticosteroids, even at low doses, are at risk for osteoporosis. In both groups, additional factors such as hypogonadism might be responsible for low BMD and low osteocalcin levels. A decrease in bone formation is a possible mechanism of action.

Adrenal Cortex Hormones↗
PubMed1992

Time related bias in longitudinal studies using dual photon absorptiometry.

Examining the bone mineral density (BMD's) slope of patients regularly followed in our department, we observed recently that the group of patients who had their last BMD during the last 6 months of 1989, had a different slope than patients who had their last BMD during the following 6 months. In order to investigate if a small time-related bias of measurement, unsuspected by the former quality control investigations, could exist, we performed the following analyses. A regression equation between BMD and time was calculated and a slope was obtained for 95 women who had been followed for at least 3 yr and had had at least 3 BMD measurements during that time. The women were divided in 3 groups according to when the last BMD measurement had been performed (July-December 1989, January-June 1990 or July-December 1990). The slopes of the 3 groups of patients were compared. For each value of BMD of every patient, a predicted BMD (BMDp) was calculated using the regression equation and the relative difference (RD) between BMDp and BMD was calculated and analysed in relation to time. There was a significant difference (p < 0.05) between the slopes of patients in relation to the time when the last BMD had been measured. Significant fluctuations (p < 0.001) in RD were observed in relation to time. These RD variations suggested the existence of a time-related error. The presence of this error is also substantiated by the fact that a parallelism existed between the curve of the RD variations and the curve of the mean values of BMD of all patients referred to our department, calculated per period of 4 months. Although the fluctuation of the latter curve was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1991

Interest of zinc determination in leucocyte fractions for the assessment of marginal zinc status.

In order to test the sensitivity of leucocyte zinc determination in the assessment of zinc status, an isolation procedure of mononuclear (MNC) and polymorphonuclear (PMNC) cell fractions was developed. Zinc concentrations in cells from healthy subjects were (mean +/- SD, in mumol/10(10) cells): 0.81 +/- 0.24 in MNC and 0.55 +/- 0.06 in PMNC. In patients suffering from several diseases known to be associated with a marginal impairment in zinc status (cirrhosis, cancer, obesity, endocrine and rheumatic diseases), these concentrations did not differ from those in controls except in rheumatic patients in whom MNC zinc was increased (1.05 +/- 0.42 mumol/10(10) cells) and correlated with erythrocyte sedimentation rate (r = 0.41, P less than 0.01). This relation was also significant in the whole study population (r = 0.39, P less than 0.01). Leucocyte zinc therefore appears to have a limited value in the assessment of marginally impaired zinc status, except in inflammatory states.

Adult↗
PubMed1991

Effects of acute and chronic prednisolone treatment on serum zinc levels in rats with adjuvant arthritis.

Several studies in animals and humans have independently demonstrated that zinc metabolism is significantly affected either by inflammation or by glucocorticoid administration. The relative importance of these two factors was assessed in this study by the investigation of the effects on serum zinc concentrations of acute and chronic prednisolone treatments in adjuvant arthritis rats and in healthy controls animals. Acute steroid administration (3 mg/kg, i.p.) caused a rapid drop in serum zinc followed by a quick recovery, regardless to the fact that these concentrations were normal (healthy animals) or already reduced by the inflammatory process. However, the modification occurred faster in inflamed animals. Chronic steroid administration (0.58 to 0.78 mg/kg/day during 1 to 4 weeks) had a more complex effect. A previous experiment in healthy rats demonstrated that such a treatment only induced a slight decrease in serum zinc. In adjuvant arthritis animals, the early steroid treatment of the induced process promoted a further decrease in serum zinc level while a delayed treatment did not result in additional changes.

Animals↗
PubMed1991

Lymphocyte response is enhanced by supplementation of elderly subjects with selenium-enriched yeast.

The effect of selenium supplementation on plasma selenium concentrations and lymphocyte-proliferation responses to mitogens was investigated in 22 elderly institutionalized subjects. Subjects were assigned to a 6-mo trial with either 100 micrograms Se/d (as selenium-enriched yeast) or a placebo. Plasma selenium concentrations of the selenium-supplemented group increased from 0.84 +/- 0.26 to 1.55 +/- 0.33 mumol/L (mean +/- SD) after 2 mo and the values plateaued thereafter. The mean response of lymphocytes to mitogens in elderly subjects tended to be lower than responses in healthy adults, although responses remained within the 5-95% confidence-interval limit for healthy adults. During selenium supplementation the proliferative response to pokeweed mitogen increased significantly (+79% of baseline concentrations after 4 mo, P less than 0.01) and reached the upper limit of the usual range for adults after 6 mo (+138%, P less than 0.001). In accordance with previous studies in animals and in vitro, this investigation demonstrates for the first time immunostimulatory properties of selenium-enriched yeast in elderly humans.

Aged↗