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C Harel

Publications and source records attributed to C Harel.

At least 19 recordsLinked to original sources
PubMed2000

Analysis of the peroxisome proliferator activated receptor gamma (PPARgamma) gene in HAIRAN syndrome with obesity.

OBJECTIVES: To test the hypothesis that the triad of hyperandrogenism, insulin resistance and acanthosis nigricans (HAIRAN syndrome) in the presence of obesity, also known as type C insulin resistance, is caused by mutations in the gene for peroxisome proliferator activated receptor gamma (PPARgamma), a receptor for the thiazolidinedione drugs that enhance sensitivity to insulin. To investigate possible correlations between mutations in PPARgamma and the degree of insulin resistance. DESIGN: A candidate gene approach to study the molecular basis for a syndrome of obesity; a comparison of genotype with in vivo phenotype. PATIENTS: Fifteen unrelated patients with HAIRAN syndrome and obesity. Controls for the gene analysis: 25 unrelated non-diabetic non-obese individuals. Controls for the metabolic studies: six unrelated patients with type 2 diabetes mellitus and nine unrelated non-diabetic non-obese individuals. MEASUREMENTS: Analysis of polymerase chain reaction (PCR) products of the 7 exons that constitute the entire coding region of both PPARgamma isoforms (PPARgamma1 and PPARgamma2) for single-stranded conformational polymorphisms (SSCP); in exons with variant patterns: restriction fragment length polymorphism (RFLP) analysis; and, where relevant, direct sequencing. Evaluation of insulin resistance using the insulin euglycaemic clamp technique. RESULTS: A synonymous substitution in codon 477 (CACHis --> CATHis) was found in one patient. A missense mutation in codon 12 of PPARgamma2 (CCAPro --> GCAAla) was found in another patient, but not in any of 25 non-diabetic, non-obese control individuals. The patient with the Pro12Ala variant had the highest steady state glucose infusion rate (SSGIR) and most marked suppression of hepatic glucose production rate (HGPR) of all of the patients studied. CONCLUSIONS: Mutations in the PPARgamma gene are unlikely to be major contributors to HAIRAN syndrome with obesity. The Pro12Ala variant may correlate with a lesser degree of insulin resistance in these patients.

Acanthosis Nigricans↗
PubMed1999

Digital subtraction angiography of the abdominal aorta and lower extremities: carbon dioxide versus iodinated contrast material.

PURPOSE: To compare the diagnostic value of carbon dioxide to that of iodinated contrast material for digital subtraction angiography of the abdominal aorta and lower extremities. MATERIALS AND METHODS: Thirty-five patients underwent comparative CO2 and iodinated contrast material arteriography of the abdominal aorta and lower extremities. For each contrast study, three independent observers evaluated the degree of opacification and percentage of stenosis of each vessel, the degree of certainty of their observations, and the overall quality of the study. Data of CO2 and iodinated studies were compared using analysis of variance for repeated measures. Interobserver and intertechnique agreements were estimated with Cohen's kappa and intraclass correlation coefficient. RESULTS: Iodine-based vascular opacification was superior to that with CO2 in the central and distal arteries (P = .02). The degree of certainty and overall quality score were higher for iodine than for CO2-based contrast studies (P = .00001). The interobserver agreement for categorizing stenoses was higher for iodine as compared to CO2-based angiography. No significant difference was observed between the mean stenosis values obtained with CO2 and iodine-based angiography in any segment. Intraclass correlation coefficient demonstrated a high degree of convergence of the two techniques for assessing the percentage of stenosis. CONCLUSION: CO2 can be used as an alternative to iodinated contrast material for obtaining arteriograms of the abdominal aorta and lower extremities for investigating atherosclerotic disease.

Aged↗
PubMed1995

Renal artery aneurysm: treatment with percutaneous placement of a stent-graft.

A stent-graft was placed percutaneously in the right renal artery of a 50-year-old woman with hypertension and a fibromuscular dysplastic lesion consisting of severe stenoses and a 1.5-cm saccular aneurysm with a wide neck. At 1-year follow-up with arteriography, arterial luminal diameter was normal and no aneurysm was depicted. The patient's blood pressure was normal without blood pressure medication.

Aneurysm↗
PubMed1995

Renal artery stenosis: evaluation of Doppler US after inhibition of angiotensin-converting enzyme with captopril.

PURPOSE: To evaluate the modifications of Doppler ultrasound waveform morphology after inhibition of angiotensin-converting enzyme with captopril to increase the sensitivity of Doppler sonography in detecting renal artery stenosis. MATERIALS AND METHODS: Sixty-two renal arteries were studied in 31 hypertensive patients who underwent Doppler scanning before and 1 hour after administration of captopril prior to undergoing angiography. Pattern recognition criteria were applied to classify the Doppler waveforms as having a normal or pulsus tardus configuration. Doppler scanning results were compared with those of arteriography. RESULTS: On the basis of recognition of the pulsus tardus, precaptopril Doppler scanning showed 13 (68%) of 19 significant renal artery stenoses found at angiography (95% confidence interval, 0.43, 0.85), whereas 19 (100%) of 19 stenoses were detected with postcaptopril Doppler scanning (95% confidence interval, 0.85, 1.0). CONCLUSION: Captopril significantly (95% confidence intervals) increases Doppler scanning sensitivity in detecting renal artery stenoses by inducing or enhancing the pulsus tardus distal to a significant renal artery stenosis.

Adult↗
PubMed1995

Modulation of the activity of glucose transporters (GLUT) in the aged/obese rat adipocyte: suppressed function, but enhanced intrinsic activity of GLUT.

To study the contribution of glucose transporters (GLUT) to insulin resistance in aging, GLUT intrinsic activity was assessed in a cell-free system. Adipocytes were isolated from 18-month-old rats and young controls and incubated either with or without 7 nM insulin. Plasma membrane (PM) and low density microsomal fractions were prepared from the cells, and GLUT levels were assessed in these fractions before and after reconstitution into liposomes. Glucose transport rates were measured in intact cells and liposomes. Functional and intrinsic activities of GLUT were assessed from the ratio between these transport rates and GLUT levels in the respective fractions. Basal 3-O-methylglucose transport rates were unaffected by aging, which is consistent with unchanged levels of GLUT in PM. Insulin-stimulated glucose transport was 60% lower in aging, as was the extent of GLUT recruitment to PM. The effect of insulin stimulation of GLUT functional activity by 6-fold at PM was attenuated by 40% in aging. Conversely, the basal intrinsic activity of GLUT was significantly enhanced in aging (by 280% and 230% in PM and density microsomal liposomes, respectively) and was further stimulated by insulin by about 160% in PM, compared to only about 117% stimulation in controls. In conclusion, our data show that insulin stimulates the intrinsic activity of GLUT in rat adipocytes, and this activity is further enhanced in aging. Impaired glucose uptake in aging can be attributed to depleted GLUT4 levels and impaired function of GLUT at the cell surface. The discrepancy observed between impaired function and enhanced intrinsic activity of GLUT suggests the presence of additional factors that modulate the full functional expression of GLUT at the cell surface.

Adipocytes↗
PubMed1994

Correction of deteriorating renal function by superselective embolization of an arcuate renal artery pseudoaneurysm.

We performed superselective embolization of an iatrogenic pseudoaneurysm of the right kidney that was causing hematuria and deterioration of renal function in a patient with chronic renal failure. An arcuate artery was embolized with absorbable gelatin sponge and a straight embolization wire without significant loss of renal vascularization, thus restoring baseline renal function. To our knowledge the clinical and technical aspects of our case are unique. The technique is described.

Aged↗
PubMed1993

Potential role for insulin and cycloheximide in regulating the intrinsic activity of glucose transporters in isolated rat adipocytes.

We examined the hypothesis that insulin stimulation of cellular glucose transport may involve a protein synthesis-dependent regulation of glucose transporter (GTer) activity independent of GTer translocation to the cell surface. Rat adipocytes were isolated, incubated with or without 10 micrograms/ml (36 microM) cycloheximide (CHX) for 60 min, and then with or without 7 nM insulin for 30 min. Glucose transport rates were assessed in intact cells, and both glucose transport rates and GTer levels were assessed in subcellular fractions of membrane vesicles before and after reconstitution into artificial liposomes. GTer functional and intrinsic activities were calculated as the ratio between these transport rates and GTer levels in native and reconstituted membranes, respectively. Insulin increased functional activity by 340% in native plasma membrane (PM) vesicles and intrinsic activity by 60% in reconstituted membranes (from 54 +/- 4 to 86 +/- 4 molecules transported per GTer/sec, P < 0.02). CHX preincubation of cells did not interfere with the insulin effect to stimulate glucose transport rate in either intact cells or in native PMs; it did, however, reduce PM GTer levels by 27-30%, but not affecting those in the intracellular pool. However, CHX additively increased the insulin-stimulated intrinsic activity of PM GTers by 67%. Relative reconstitution efficiencies, assessed by immunoblotting both native and reconstituted membranes against specific antibodies, were similar for GLUT 1 and GLUT 4. Although insulin did not alter this efficiency, CHX slightly decreased it for GLUT 4. Our data suggest that insulin stimulation of glucose transport may involve, as part of its mechanism, modulation of the GTer intrinsic activity. We further hypothesize that CHX effects on increasing this activity state of GTer may involve as yet unknown protein synthesis-dependent regulator(s).

Adipocytes↗
PubMed1990

Insulin resistance and acanthosis nigricans: evidence for a postbinding defect in vivo.

Acanthosis nigricans (AN) with insulin resistance has been traditionally attributed to insulin receptor abnormalities. To further clarify the postbinding defects of in vivo insulin action in this state, we applied the euglycemic insulin clamp technique, combined with the glucose trace infusion method, to 26 subjects: 12 AN patients (eight normoglycemic and four hyperglycemic), eight obese, and eight lean control subjects. The normoglycemic AN group exhibited fasting hyperinsulinemia (666% of control), 160% elevated hepatic glucose production (HGP), 425% increased posthepatic insulin delivery rate, and only slightly reduced (19%) insulin clearance rates, compared with controls. Except for the latter, all these abnormalities were statistically significant (P less than .05), and could not be accounted for by body overweight. AN patients with diabetes mellitus (AN + DM) exhibited a further decreased insulin responsiveness (30%) and clearance (38%), together with a major increase in HGP (320%). All AN patients showed a significant right-shift in the insulin dose-response curve, indicating a decrease in insulin sensitivity. In conclusion, AN is characterized by increased basal rates of HGP, and peripheral insulin resistance, which can be partially attributed to postbinding defects. In AN + DM, a worsening of these abnormalities may be responsible for unmasking the existence of diabetes.

Acanthosis Nigricans↗
PubMed1986

Bronchial angiography: a report of 21 patients.

Angiographic studies of the bronchial and other systemic thoracic arteries were requested by referring physicians in 21 patients, in 18 cases because of hemoptysis. Selective catheterization was carried out in 18 of the 21, and in an additional two patients the bronchial arteries were identified by thoracic aortography. Five examples of effective therapeutic embolization are discussed. Bronchial angiography and embolization appear to be of value in the diagnosis and treatment of hemoptysis.

Aged↗