The nickel released from jewelry in Israel and its clinical relevance.
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Dermatitis, Allergic Contact↗
Biomedical subjects
S Klein
Publications and source records attributed to S Klein.
Training-induced alterations in fat and carbohydrate metabolism during exercise in elderly subjects.
Compared with young adults, fat oxidation is lower in elderly persons during endurance exercise performed at either the same absolute or relative intensity. We evaluated the effect of 16 wk of endurance training on fat and glucose metabolism during 60 min of moderate intensity exercise [50% of pretraining peak oxygen consumption (VO2peak)] in six elderly men and women (74 +/- 2 yr). Training caused a 21% increase in mean VO2peak. The average rate of fat oxidation during exercise was greater after (221 +/- 28 mumol/min) than before (166 +/- 17 mumol/min) training (P = 0.002), and the average rate of carbohydrate oxidation during exercise was lower after (3,180 +/- 461 mumol/min) than before (3,937 +/- 483 mumol/min) training (P = 0.003). Training did not cause a significant change in glycerol rate of appearance (Ra), free fatty acid (FFA) Ra, and FFA rate of disappearance during exercise. However, glucose Ra during exercise was lower after (1,027 +/- 95 mumol/min) than before (1,157 +/- 69 mumol/min) training (P = 0.01). These results demonstrate that a 16-wk period of endurance training increases fat oxidation without a significant change in lipolysis (glycerol Ra) or FFA availability (FFA Ra) during exercise in elderly subjects. Therefore, the training-induced increase in fat oxidation during exercise is likely related to alterations in skeletal muscle fatty acid metabolism.
Aged↗
Whole body, adipose tissue, and forearm norepinephrine kinetics in lean and obese women.
We evaluated whole body and regional (subcutaneous abdominal adipose tissue and forearm) norepinephrine (NE) kinetics in seven lean (body mass index 21.3 +/- 0.5 kg/m2) and six upper body obese (body mass index 36.4 +/- 0.4 kg/m2) women who were matched on fat-free mass. NE kinetics were determined by infusing [3H]NE and obtaining blood samples from a radial artery, a deep forearm vein draining mostly skeletal muscle, and an abdominal vein draining subcutaneous abdominal fat. Mean systemic NE spillover tended to be higher in obese (2.82 +/- 0.49 nmol/min) than in lean (2.53 +/- 0.40 nmol/min) subjects, but the differences were not statistically significant. Adipose tissue and forearm NE spillover rates into plasma were greater in lean (0.91 +/- 0.08 pmol. 100 g tissue-1. min-1 and 1.01 +/- 0.09 pmol. 100 ml tissue-1. min-1, respectively) than in obese (0.26 +/- 0.05 pmol. 100 g tissue-1. min-1 and 0.58 +/- 0.11 pmol. 100 ml tissue-1. min-1, respectively) subjects (P < 0.01). These results demonstrate that adipose tissue is an active site for NE metabolism in humans. Adipose tissue NE spillover is considerably lower in obese than in lean women, which may contribute to the lower rate of lipolysis per kilogram of fat mass observed in obesity.
Adipose Tissue↗
Early magnetic resonance imaging of brainstem lesions after severe head injury.
OBJECT: The availability of magnetic resonance (MR) imaging data obtained in comatose patients after head injury is scarce, because MR imaging is somewhat cumbersome to perform in patients requiring ventilation and because, in the first hours after injury, its relevance is clearly inferior to computerized tomography (CT) scanning. The authors assessed the value of MR imaging in the early postinjury period. METHODS: In this prospective study MR imaging was performed in 61 consecutive patients within 7 days after they suffered a severe head injury. An initial CT scan had already been obtained. To understand the clinical significance of the lesions whose morphological appearance was identified with MR imaging, brainstem function was assessed by registration of somatosensory and auditory evoked potentials. Brainstem lesions were visualized in 39 patients (64%). Bilateral pontine lesions proved to be 100% fatal and nonbrainstem lesions carried a mortality rate of 9%. In singular cases circumstances allowed for a clear clinical distinction between primary and secondary brainstem lesions. On MR imaging all lesions were hyper- and hypointense after intervals longer than 2 days. Within shorter intervals (< 2 days) after the injury, primary lesions appeared isointense on MR imaging. In one secondary brainstem lesion there were no traces of blood. CONCLUSIONS: Because mean intracranial pressure (ICP) levels in patients without brainstem lesions were similar to those in patients with brainstem lesions, the authors conclude that it was not mainly increased ICP that accounted for the high mortality rates in patients with brainstem lesions. The authors also conclude that brainstem lesions are more frequently found in severe head injury than previously reported in studies based on neuropathological or CT scanning data. Early MR imaging after head injury has a higher predictive value than CT scanning.
Adult↗
Spontaneous murine lung adenocarcinoma (P07): A new experimental model to study paraneoplastic syndromes of lung cancer.
We report the histological and biological behavior characteristics of a lung tumor (P07) that arose spontaneously in a Balb/c mouse. P07 is a moderately to poorly differentiated adenocarcinoma that secretes granulocyte-macrophage colony stimulating factor (GM-CSF) in culture supernatants. This tumor presents some paraneoplastic syndromes, such as leukocytosis, hypercalcemia and cachexia. taken together with the peripheral blood leukocyte (PBL) counts and serum calcium levels during s.c. tumor growth and after surgery, this study suggests that P07 may be a useful experimental model to study the biology of lung cancer and paraneoplastic syndromes.
Adenocarcinoma↗
Measurement of plasma glycerol specific activity by high performance liquid chromatography to determine glycerol flux.
Previous methods for measuring plasma glycerol specific activity (SA) are suboptimal, making the determination of glycerol kinetics in vivo with radiotracers difficult. A new high performance liquid chromatography (HPLC) method is described that permits the accurate and specific measurement of glycerol SA. The method involves isolation of glycerol from plasma and the formation of a tribenzoyl derivative. Glycerol rate of appearance was measured in five human volunteers using both [2-3H]glycerol and [2H5] glycerol. There was close agreement between the glycerol appearance rates measured using the two approaches (1.66 +/- 0.14 vs. 1.70 +/- 0.10 micromol x kg(-1) x min(-1), respectively, P = NS). This HPLC method offers improved specificity over existing methods of measuring glycerol turnover using radiotracers.
Chromatography, High Pressure Liquid↗
Sex and electroencephalographic synchronization after photic stimulation predict signal changes in the visual cortex on functional MR images.
PURPOSE: We evaluated factors that influence MR signal changes during photic stimulation of the visual cortex. We also tested the hypothesis that functional MR imaging response corresponds to electroencephalographic (EEG) synchronization after photic stimulation. METHODS: Thirty-eight healthy subjects, 20 men and 18 women, underwent photic stimulation of the visual cortex. They were studied with a 1.5-T MR unit, and photic stimulation was induced via 8-Hz LED goggles. Seven subjects with and seven without detectable functional MR imaging response to photic stimulation underwent further studies with 16-channel EEG after 2- to 30-Hz stroboscopic stimulation. RESULTS: Thirteen men and 18 women had a significant increase in MR signal in the visual cortex; seven men showed no visual cortex activation during more than two repeated studies. Six of seven volunteers with increased functional MR imaging signal after photic stimulation also showed signs of EEG synchronization when an 8-Hz stroboscopic flash was used; six of seven subjects with no functional MR imaging lacked EEG synchronization at 8-Hz stimulation. CONCLUSIONS: Men were more likely than women to have undetectable MR signal changes after photic stimulation. This finding should be considered when interpreting results of functional MR imaging studies. EEG with stroboscopic examination is a good predictor of functional MR imaging sensitivity to changes in regional cerebral blood flow induced by sensory stimulation.
Adult↗
Perforated appendicitis: is it truly a surgical urgency?
Advanced perforated appendicitis with localized findings has classically been treated with either operative therapy or with percutaneous drainage. The role of nonoperative therapy followed by interval appendectomy (IA) remains controversial. We assessed the safety and efficacy of conservative management for perforated appendicitis in a 5-year review of patients treated conservatively for perforated appendicitis with localized abscess or phlegmon. Patients were treated initially with intravenous antibiotics, and CT-guided drainage was used only if the patient failed to improve after 48 to 72 hours. Patients still not improving underwent appendectomy. Patients responding to conservative therapy were recommended IA in 6 to 12 weeks. Sixty-six patients with 54 abscesses and 10 phlegmons were treated. Fifty-one patients (92%) improved without surgery. Only 58 per cent of the abscesses required percutaneous drainage. The mean length of stay for conservative therapy was 7.6 days. Forty-one patients underwent IA with a 10 per cent morbidity and a mean length of stay of 1.4 days. Conservative management of appendicitis with localized perforation or phlegmon is safe and effective. Percutaneous drainage is frequently not required. IA is associated with low morbidity without prolonged hospitalization.
Abscess↗
Signal transduction through epidermal growth factor receptor is altered in HeLa monolayer cells during mitosis.
Epidermal growth factor (EGF)-induced signalling was studied separately in the mitosis and G2-phases of HeLa monolayer cells presynchronized (1) by amethopterin inhibition and thymidine release or (2) by nocodazole. For comparison, cells were treated with the phorbol ester phorbol 12-myristate 13-acetate (PMA). In contrast with the observed responses effected by PMA, which seem to be independent of cell cycle and synchronization conditions, those induced by EGF are greatly influenced by both criteria. Synchronization with nocodazole abolished the EGF-induced stimulation of phosphoinositide hydrolysis in G2 as well as in mitotic cells although tyrosine phosphorylation of the EGF receptor and phospholipase Cgamma1 could be shown to occur, especially in G2 cells. Synchronization with amethopterin/thymidine showed that, in contrast with G2 cells, mitotic cells were not able to react to EGF with an increase in phosphoinositide hydrolysis although a certain degree of EGF receptor dimerization and autophosphorylation as well as tyrosine phosphorylation of phospholipase Cgamma1 could still be shown to occur in mitosis. The results seem to indicate that the EGF pathway leading to a stimulation of phosphoinositide hydrolysis is attenuated at different levels and requires a cytoskeletal condition that is not present either after treatment (24 h) with nocodazole or during normal mitosis of a monolayer cell.
Antineoplastic Agents↗
O6-alkylguanine DNA alkyltransferase activity in student embalmers.
O6-Alkylguanine-DNA alkyltransferase (AGT) activity was assessed in peripheral blood lymphocytes among 23 mortuary science students before and after 9 weeks in a laboratory course in techniques of embalming. Formaldehyde exposure was established by environmental monitoring. The average air concentration of formaldehyde during embalming was about 1.5 ppm. At the pre-exposure sampling, baseline DNA repair capacity tended to be reduced in subjects who reported a prior history of embalming (p = 0.08). From pre- to post-exposure, 17 subjects decreased in DNA repair capacity, while only 6 increased (p < 0.05). Analysis of variance, including adjustment for age, sex, and smoking status, confirmed these findings. Among the eight subjects who had no embalming experience during the 90 days before study, seven had decreased and one had increased AGT activity during the period of study (p < 0.05). For those with prior embalming experience, 10 subjects decreased in AGT activity, while 5 increased (p < 0.05). Although the major chemical exposure in embalming practice was to formaldehyde, no clear link was established between amount of formaldehyde exposure and AGT activity.
Adult↗
Effects of beta-carotene and other factors on outcome of cervical dysplasia and human papillomavirus infection.
Women with histopathologically confirmed cervical intraepithelial neoplasia (CIN) were followed at 3-month intervals in a randomized double-blinded trial to evaluate the efficacy of beta-carotene to cause regression of CIN. Questionnaire data, plasma levels of micronutrients, and a cervicovaginal lavage for human papillomavirus (HPV) detection were obtained at each visit, and an endpoint biopsy was performed at 9 months. Sixty-nine subjects had a biopsy endpoint evaluation; 9 of 39 (23%) subjects in the beta-carotene group versus 14 of 30 (47%) in the placebo group had regression of CIN (P = 0.039). Independent risk factors for persistent CIN at 9 months included type-specific persistent HPV infection (OR = 11.38, P = 0.006) and continual HPV infection with a high viral load (OR = 14.25, P = 0.007) at baseline and 9 months, an initial diagnosis of > or =CIN II (OR = 6.74, P = 0.016), and older age (OR for > or =25 years = 4.10, P = 0.072). After controlling for these factors, the beta-carotene and placebo groups did not differ in risk for having CIN at 9 months (OR = 1.53, P = 0.550). Resolution of baseline HPV infection was significantly correlated with non-high-risk HPV types (RR = 2.94, P = 0.015), age <25 years (RR = 2.62, P = 0.014), and douching after sexual intercourse (RR = 3.02, P = 0.012), but not with randomization group. Our data indicate that a large proportion of mild CIN lesions regress; age and HPV infection play an important role in the natural course of CIN; and repeated HPV testing may have a value in distinguishing women who need aggressive treatment for CIN versus those who do not. Supplementation of beta-carotene does not appear to have a detectable benefit in treatment of CIN.
Adult↗
Fibroblast growth factors as angiogenesis factors: new insights into their mechanism of action.
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Animals↗
Obstetric antecedents of intraventricular hemorrhage and periventricular leukomalacia in the low-birth-weight neonate.
OBJECTIVE: Neonatal intraventricular hemorrhage and periventricular leukomalacia have a strong correlation with eventual neurologic deficit. Our objective was to correlate obstetric factors with the development of these lesions. STUDY DESIGN: Seven hundred forty-five consecutive inborn neonates with birth weights from 500 to 1750 gm were divided into three clinical groups: premature rupture of membranes, refractory preterm labor with intact membranes, and delivery initiated by the physician for maternal or fetal indications. Neonatal neurosonography was performed on days 3 and 7 of life and results were described as normal or abnormal. Abnormal scans included intraventricular hemorrhage seen within 3 days and echodense or echolucent periventricular leukomalacia seen within 7 days of life. Major abnormalities included intraventricular hemorrhage grades 3 and 4, intraventricular hemorrhage with periventricular leukomalacia, and echolucent periventricular leukomalacia. Abnormal scans were correlated with groups of origin and clinical and histologic chorioamnionitis. RESULTS: Abnormal scans occurred in 33% of cases of premature rupture of membranes and in 38.9% of cases of preterm labor compared with 17.7% of physician-initiated cases (p < 0.000001). Major lesions occurred in 17.6% of cases of premature rupture of membranes, 21.4% of cases of preterm labor, and 1.1% of physician-initiated cases (p < 0.0000001). Clinical chorioamnionitis occurred in 19.7% of cases of premature rupture of membranes, 11.9% of cases of preterm labor, and 1.1% of physician-initiated cases (p < 0.001) and was associated with a significant increase in the incidence (p < or = 0.005) and severity (p < or = 0.007) of these lesions. Histologic chorioamnionitis occurred in 59.9% of cases of premature rupture of membranes, 43.2% of cases of preterm labor, and 8% of physician-initiated cases and did not correlate significantly with the incidence or severity of abnormal scans. These findings were independent of gestational age. CONCLUSIONS: The incidence and severity of intraventricular hemorrhage and periventricular leukomalacia were significantly increased in premature rupture of membranes and preterm labor compared with the physician-initiated cases. Clinical chorioamnionitis increased the incidence and severity of these lesions.
Cerebral Hemorrhage↗
Measurement of very low stable isotope enrichments by gas chromatography/mass spectrometry: application to measurement of muscle protein synthesis.
Measurement of muscle protein synthesis using stable isotopically labeled tracers usually requires isotope ratio mass spectrometry (IRMS) because of the need to measure very low enrichments of stable isotopically labeled tracers (tracer to tracee ratio [TTR], 0.005% to 0.10%). This approach is laborious, requiring purification of the metabolite of interest and combustion to a gas for IRMS analysis, and is best suited for use with 13C tracers. We have developed an approach whereby low enrichments can be conveniently measured by a conventional gas chromatography/mass spectrometry (GC/MS) instrument. The approach includes three critical elements: (1) use of a highly substituted tracer containing three or more labeled atoms, to measure enrichment above a very low natural abundance of highly substituted isotopomers; (2) use of a highly substituted natural abundance isotopomer as a base ion for comparison rather than the most abundant m + 0 isotopomer, to reduce the dynamic range of the isotopomer ratio measurement; and (3) a sensitive mass spectrometric analysis that measures the natural abundance of the isotopomer used as a tracer with a high signal to noise ratio (> 100:1). This approach was used to measure the rate of synthesis of muscle protein following a primed continuous infusion of L-[13C6]-phenylalanine (PHE) in eight fasted dogs and L-[2H3]-leucine in five fasted human subjects. Values for [13C6]-PHE enrichment by GC/MS rates were virtually identical to those obtained by a conventional approach using high-performance liquid chromatography (HPLC) to isolate PHE, combustion to CO2, and measurement of 13CO2 enrichment by IRMS (IRMS enrichment = 0.9988 x GC/MS enrichment, R2 = .891), resulting in identical values for muscle fractional synthesis rates ([FSRs] mean +/- SEM: 2.7 +/- 0.2 and 2.5 +/- 0.2%/d for GC/MS and IRMS, respectively). Human muscle synthesis rates measured by GC/MS analysis of [2H3]-leucine enrichment (1.90 +/- 0.17%/d) were similar to published values based on IRMS analysis using a 1- 13C-leucine tracer. We conclude that compared with the IRMS approach, the GC/MS approach offers faster throughput, has a lower sample requirement, and is suitable for a wider variety of tracers such as 2H. The principles outlined here should be applicable to the measurement of low enrichments by GC/MS in a wide variety of stable isotope tracer applications.
Adult↗
Lipolytic sensitivity and response to fasting in normotensive and hypertensive obese humans.
Obese persons with hypertension are at greater risk for diabetes and hyperlipidemia than normotensive obese persons. It has been postulated that increased lipolytic rates contribute to these metabolic diseases. Therefore, we evaluated the glycerol rate of appearance (Ra) in plasma, an index of whole-body lipolytic activity, during basal conditions and during 60 minutes of epinephrine infusion after 12 and 84 hours of fasting in six normotensive (body mass index [BMI], 39.9 +/- 1.8 kg/m2) and six hypertensive (BMI, 38.7 +/- 1.6 kg/m2) obese persons. Basal glycerol Ra was lower in hypertensive than in normotensive subjects at both 12 hours (1.58 +/- 0.21 v 2.27 +/- 0.28 mumol/kg/min, respectively; P < .01) and 84 hours (2.04 +/- 0.06 v 2.50 +/- 0.13 mumol/kg/min, respectively; P < .01) of fasting. Peak glycerol Ra during epinephrine infusion after 84 hours of fasting (5.69 +/- 0.72 and 11.40 +/- 0.78 mumol/kg/min for hypertensive and normotensive subjects, respectively) was significantly greater than at 12 hours (3.09 +/- 0.29 and 5.06 +/- 0.69 mumol/kg/min) in both hypertensive and normotensive subjects. However, peak glycerol Ra was lower in hypertensive than in normotensive subjects after 12 and 84 hours of fasting (P < .01 for 84 hours). We conclude that hypertension in obese persons is associated with a decrease in both basal lipolytic rates and lipolytic sensitivity to epinephrine infusion.
Adult↗
Nutrition support in clinical practice: review of published data and recommendations for future research directions.
In the last 30 years, marked advances in enteral feeding techniques, venous access, and enteral and parenteral nutrient formulations have made it possible to provide nutrition support to almost all patients. Despite the abundant medical literature and widespread use of nutritional therapy, many areas of nutrition support remain controversial. Therefore, the leadership at the National Institutes of Health, The American Society for Parenteral and Enteral Nutrition, and The American Society for Clinical Nutrition convened an advisory committee to perform a critical review of the current medical literature evaluating the clinical use of nutrition support; the goal was to assess our current body of knowledge and to identify the issues that deserve further investigation. The panel was divided into five groups to evaluate the following areas: nutrition assessment, nutrition support in patients with gastrointestinal diseases, nutrition support in wasting diseases, nutrition support in critically ill patients, and perioperative nutrition support. The findings from each group are summarized in this report. This document is not meant to establish practice guidelines for nutrition support. The use of nutritional therapy requires a careful integration of data from pertinent clinical trials, clinical expertise in the illness or injury being treated, clinical expertise in nutritional therapy, and input from the patient and his/her family.
Journal Article↗
Switching yeast from meiosis to mitosis: double-strand break repair, recombination and synaptonemal complex.
BACKGROUND: When Saccharomyces cerevisiae cells that have begun meiosis are transferred to mitotic growth conditions ('return-to-growth', RTG), they can complete recombination at high meiotic frequencies, but undergo mitotic cell division and remain diploid. It was not known how meiotic recombination intermediates are repaired following RTG. Using molecular and cytological methods, we investigated whether the usual meiotic apparatus could repair meiotically induced DSBs during RTG, or whether other mechanisms are invoked when the developmental context changes. RESULTS: Upon RTG, the rapid disappearance of meiotic features--double-strand breaks in DNA (DSBs), synaptonemal complex (SC), and SC related structures-was striking. In wild-type diploids, the repair of meiotic DSBs during RTG was quick and efficient, resulting in homologous recombination. Kinetic analysis of double-strand breakage and recombination indicated that meiotic DSB formation precedes the commitment to meiotic levels of recombination. DSBs were repaired in RTG in dmc1, but not rad51 mutants, hence repair did not occur by the usual meiotic mechanism which requires the Dmc1 gene product. In haploids, DSBs were also repaired quickly and efficiently upon RTG, showing that DSB repair did not require the presence of a homologous chromosome. In all strains examined, SC and related structures were not required for DSB repair or recombination following RTG. CONCLUSIONS: At least two pathways of DSB repair, which differ from the primary meiotic pathway(s), can occur during RTG: One involving interhomologue recombination, and another involving sister-chromatid exchange. DSB formation precedes commitment to recombination. SC elements appear to prevent sister chromatid exchange in meiosis.
Cell Cycle Proteins↗
The centennial year: the development of important ideas during the last 100 years. Nutrition and the gastroenterologist: the last 100 years.
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Animals↗