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Biomedical subjects

J Levy

Publications and source records attributed to J Levy.

At least 271 records · Page 15Linked to original sources

Childhood minimal change disease and focal segmental glomerulosclerosis: a continuous spectrum of disease? Pathologic study of 33 cases with long-term follow-up.

Thirty-three children with idiopathic nephrotic syndrome who underwent kidney needle biopsy were reevaluated. The male to female ratio was 2:1, and a preponderance of North-African Jewish and Arab origin over Ashkenazi Jewish origin was noted. There was a positive correlation between the severity of glomerular changes and prognosis among the 10 cases with minimal change disease (MCD) and the 23 with focal segmental glomerulosclerosis (FSGS). On long-term follow-up (mean over 11 years) chronic renal failure developed in none of 10 MCD patients, 1 of 12 FSGS patients with mild glomerular sclerosis, 1 of 7 FSGS patients with moderate glomerular sclerosis and 3 of 4 FSGS patients with severe glomerular sclerosis. Prognosis of patients with mild glomerular sclerotic lesion on light microscopy was substantially not worse than the prognosis of patients with mild glomerular alterations only on the electron microscopic study (MCD-B). Thus, both pathologically and prognostically, there was a continuous spectrum from 'pure' MCD (MCD-A) to FSGS with severe glomerular sclerosis. Glomerular changes confined to the origin of the proximal tubule ('tip' changes) were seen only in 4 patients and did not have a distinct prognostic significance. No case of peripheral location of the sclerotic segment within the glomerulus was found in our series of FSGS, and therefore no correlation between location of segmental sclerosis and prognosis was feasible.

Biopsy↗

Protective effect of theophylline on bronchial hyperresponsiveness in patients with allergic rhinitis.

Disorders of the upper respiratory tract, particularly allergic rhinitis are commonly associated with bronchial hyperresponsiveness. The latter may be responsible for chronic cough, a common symptom in patients with allergic rhinitis, which, as previously shown, can be the sole presenting manifestation of bronchial hyperresponsiveness. Theophylline is widely used in patients with asthma for its bronchodilator effect, whereas its action on bronchial reactivity is controversial. The aim of this study was to determine the effect of theophylline administration on bronchial hyperresponsiveness in patients with allergic rhinitis complaining of chronic cough. Fourteen patients were studied. All of them were judged atopic on the basis of positive skin tests to common allergens. During control, spirometry, flow-volume curves and specific airway conductance (SGaw) were measured. Bronchial challenges were then performed with increasing concentrations of carbachol, and dose-response curves were constructed. The concentration of carbachol, which decreased SGaw by 35% from baseline (PD35) was determined by interpolating from the dose-response curve. After control measurements patients received in a randomized, double-blind crossover fashion either theophylline 10 mg/kg/day orally or placebo for 30 days. Measurements were then redone. After a washout period of 8 days the measurements were repeated, and patients received theophylline or placebo for a second period of 30 days. Measurements were again performed at the end of this last study period. During control all patients had normal baseline lung function data and showed marked bronchial hyperresponsiveness, PD35 amounting to 26 +/- 7 micrograms of carbachol (normal value greater than 160 micrograms). No significant changes in PD35 were noted after placebo and washout when compared with control values.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Failure to confirm the presence of a retrovirus in cultured lymphocytes from patients with Kawasaki syndrome.

We and others previously reported DNA polymerase activity in culture supernatants of peripheral blood mononuclear cells from patients with acute Kawasaki syndrome (KS). In the present study, we further characterized the previously detected polymerase activity and attempted to confirm its presence in cultured peripheral blood mononuclear cells from additional patients with KS. Characterization experiments indicated that the polymerase activity was typical of a DNA-dependent DNA polymerase rather than viral reverse transcriptase. Peripheral blood mononuclear cell cultures from 17 additional KS patients were negative for reverse transcriptase activity in three laboratories. Our findings do not provide support for a retroviral etiology of KS. Further studies should continue to focus on infectious agents in efforts to elucidate the etiology of KS.

Cells, Cultured↗

Molecular events involved in ionizing radiation induced skin carcinogenesis.

The process of mouse skin tumor formation is subdivided into three operational stages. These stages include initiation, promotion and progression. Ionizing radiation has been found to be a weak initiating agent in the production of malignant squamous cell carcinomas, a complete carcinogen and an agent effective in causing tumor progression. Four skin tumor histologies have been seen with ionizing radiation: benign papillomas, squamous (SCC) and basal (BCC) cell carcinomas and fibrosarcomas. Distinct non-ras transforming genes have been detected in radiation initiated SCCs. A benign papilloma cell line (308) was used as a model system to study ionizing radiation induced progression. A variant 308 cell line (308 10 Gy 5) derived by irradiation of the parental 308 cell has been characterized. The 308 10 Gy 5 cells unlike the parental 308 cells form malignant tumors in athymic nude mice upon subcutaneous injection. The variant 308 10 Gy 5 cells unlike the parental cells also show by northern analysis high steady state levels of the following gene transcripts: stromelysin, metallothionein II A and the proto-oncogenes c-fos and c-jun. Transient transfection studies with a chimeric mouse stromelysin promoter sequence upstream of a chloramphenicol (CAT) reporter gene into 308 and 308 10 Gy 5 cells indicated that the stromelysin promoter was constitutively active in the 308 10 Gy 5 but not in the 308 cells. The ability to divide the process of carcinogenesis into multiple stages in the mouse skin mode has facilitated mechanistic studies that may elucidate the molecular pathways involved in radiation induced tumor development.

Animals↗

The gastrointestinal tract in Down syndrome.

Down Syndrome is recognized as one of the most common predisposing conditions for a group of serious gastrointestinal (GI) anomalies. Tracheo-esophageal fistula, duodenal obstruction with or without pyloric stenosis, annular pancreas, imperforate anus and Hirschsprung's disease are the most prevalent lesions. Understanding of the morphogenetic mechanisms responsible for this range of abnormalities is far from clear, as none of the lesions is specific to the trisomic state and the underlying defects (i.e., failure of foregut canalization, failure of neural crest cell migration into the myenteric and submucosal plexuses or malformation of the anterior abdominal wall, etc) are encountered in unaffected infants. Segregation analysis of inheritance patterns points to multi-factorial traits and random genetic action provide appropriate models (to a certain extent) for describing the observations. Furthermore, intestinal anomalies can be found in many other genetic disorders, with recent evidence suggesting the presence of GI developmental regulatory genes on chromosome 13q. A possible common pathway to the observed anomalies might be enhanced epithelial adhesiveness, as demonstrated in vitro experiments with fibroblasts. Molecular genetic techniques applied to the smallest human autosome could provide the needed insight into the ultimate mechanisms determining morphogenesis. The development of a murine model is a promising tool for the successful approach to these extraordinarily complex questions.

Digestive System↗

Impact of Phase I Pew National Dental education Program on U.S. schools of dental medicine.

This paper presents the results of four telephone surveys conducted by the Leonard Davis Institute of Health Economics (LDI), University of Pennsylvania, as part of its evaluation of the Pew National Dental Education Program (PNDEP), a five year, +4F8.7 million program established by The Pew Charitable Trusts to help dental schools respond to the changing health care environment. The four annual surveys were conducted between 1985 and 1988. The interviews were conducted with the deans from nearly all dental schools operating in the United States at the time of study or the principal investigators of the schools funded under Phase I and Phase II PNDEP grants. Their purpose was to determine the level of each school's involvement in PNDEP and in specific strategic planning activities, as well as to evaluate the impact of the Pew Program on both the individual schools and dental education nationwide. All systematic differences between schools funded (FD) PNDEP and those not funded (NFD) were examined. Overall, schools gained a better understanding of their environment. Schools also reported increased participation in and commitment to planning among their different constituencies (e.g., faculty, administration, students, alumni). By the end of Phase I, more PNDEP Phase I funded schools reported being involved in implementing strategic plans. Funded schools also were more likely to report PNDEP increased their understanding of strategic planning, improved communication, and helped encourage the emergence of new leaders.

Administrative Personnel↗

GTP analogues cause preferential translocation of an 18 kDa cytosolic G-protein to the membrane fraction in the ZR-75-1 human breast-cancer cell line.

Several G-proteins (GTP-binding proteins) were identified by SDS/PAGE in the cytosol (105,000 g supernatant) and membrane fractions of the oestrogen-dependent human mammary-tumour cell line ZR-75-1. These proteins, with molecular masses in the range 18-29 kDa, specifically bind [alpha-32P]GTP, which can be displaced by unlabelled GTP, GDP and their non-hydrolysable analogues guanosine 5'-[delta-thio]triphosphate (GTP[S]) and guanosine 5'-[beta-thio]diphosphate (GDP[S]), but not by GMP, ATP, ADP, AMP and other unrelated nucleotides. The apparent dissociation constant for GTP was approx. 2 x 10(-8)M. Homogenization of ZR-75-1 cells in high-salt buffer (1 M-KCl), and successive washing of the membrane fraction, suggested that, among the major G-proteins found, the 18 kDa protein is predominantly soluble, whereas the 27-29 kDa complex is primarily bound to the membrane fraction under the experimental conditions employed. Possible translocation of these G-proteins between membrane and cytosol was analysed. No redistribution of the 27-29 kDa complex was observed, whereas GTP[S] in the presence of Mg2+ caused apparent translocation of the 18 kDa protein to the membrane fraction. This effect was specific for GTP and stable GTP analogues, whereas GDP, GMP, ATP, ADP, AMP and other unrelated nucleotides were ineffective. GTP[S] and guanosine 5'-[beta gamma-imido]-triphosphate (p[NH]ppG) were equally potent (apparent Kd approximately 5 x 10(-6)M), whereas GTP was rather weak. The nucleotide effect is temperature-, time- and concentration-dependent. The translocation process was reversible, slow, and reached its maximum between 30 and 60 min at 37 degrees C. The apparent translocation of this small G-protein from the cytosol to the membrane fraction, and the specific effect of GTP analogues, suggest that this process may have functional significance in mammary-tumour cells.

Biological Transport↗

Is "Campylobacter upsaliensis" an unrecognised cause of human diarrhoea?

For 3 years a filtration system for the isolation of "new" campylobacter was included in the culture protocol of 15,185 stool specimens. "C upsaliensis" was isolated in 99 patients, C jejuni subsp doylei in 4, and C hyointestinalis in 2. "C upsaliensis" was the only organism isolated in 83 patients. Clinical information was available for 77 out of these 83 patients. 92% of the patients had diarrhoea; vomiting and fever were rare (14% and 7%, respectively); the onset was mostly sudden; and the symptoms usually lasted for less than a week. Gross or occult blood was present in a quarter of cases and neutrophils were detected in faecal smears in about a fifth. "C upsaliensis" may be an unrecognised and frequent cause of diarrhoea in man, and selective isolation media should be combined with non-selective isolation systems.

Adult↗

Diacylglycerols modulate phosphorylation of the insulin receptor from human mononuclear cells.

It has been found that 1,2- but not 1,3-diacylglycerols stimulated phosphorylation of the insulin receptor of cultured human monocyte-like (U-937) and lymphoblastoid (IM-9) cells both in the intact- and broken-cell systems. The stimulation of the receptor's beta-subunit phosphorylation was dose-dependent, with optimal effect at 100 micrograms/ml of diacylglycerol. The effects of insulin and 1,2-diacylglycerols on the phosphorylation of partially purified insulin receptors were additive. Phosphoamino acid analysis showed a major effect of diacylglycerols on phosphorylation of tyrosine residues. The diacylglycerols also stimulated tyrosine kinase activity of the partially purified U-937 and IM-9 insulin receptors 2.5-3.5-fold when measured by phosphorylation of an exogenous substrate, poly(Glu80Tyr20) in the absence of any added insulin, calcium or phospholipid. Since this diacylglycerol effect could not be reproduced under conditions optimal for protein kinase C activation and the purified protein kinase C did not stimulate phosphorylation of the beta-subunit of the insulin receptor in this system, it is unlikely that the diacylglycerol effect was mediated by protein kinase C. Since these exogenous 1,2-diacylglycerols at the same high concentration also inhibited 125I-insulin binding to the insulin receptor of the intact U-937 and IM-9 cells, diacylglycerols could modulate the function of the insulin receptor and insulin action in human mononuclear cells.

Cell Line↗

Lymph node enlargement as a sign of acute hepatitis A in children.

Abdominal ultrasound was performed in 58 children presenting with proven acute hepatitis A and in 63 controls of the same age. There are well-known echographic signs of hepatitis (liver enlargement, gallbladder wall thickening, periportal hyperechogenicity) but they were not constantly found. We describe in all the hepatitis cases an enlargement of lymph nodes located in the hepatic hilum, pancreatic area and small omentum: they appeared hyperechogenic at the centre with hypoechogenic outer layer. Such enlarged lymph nodes were not observed in the controls.

Acute Disease↗

Cutaneous photosensitivity and coproporphyrin abnormalities in the Alagille syndrome.

Porphyria cutanea tarda-like blistering, fragility, and scarring of light-exposed skin was observed in four children with the Alagille syndrome. Abnormally elevated levels of serum porphyrins, of which coproporphyrin isomers I and III together accounted for 50%-89% of the total, were found in these four children but also in three other children with the Alagille syndrome without such skin lesions. The ratio for isomer I to III for total serum coproporphyrin concentration was determined in six cases; the concentration of isomer I was greater than or equal to that of isomer III in each case. Urinary total porphyrin excretion was found to be elevated in six of the seven cases, with 72% +/- 8% occurring as coproporphyrins I and III. The ratio for urinary coproporphyrin I to III was greater than or equal to 1 in six of these patients, the reverse of the typical normal isomer distribution. Inasmuch as the presence or absence of photocutaneous lesions did not correlate with levels of porphyrins in serum or urine, other factors may be involved in the pathogenesis of the skin lesions.

Adolescent↗

Obstruction of the Roux limb after portoenterostomy for biliary atresia: a delayed complication.

We report the case of a 5-year-old girl who underwent a Kasai portoenterostomy for extrahepatic biliary atresia. The conduit was exteriorized until 11 months of age. She was doing well, with stable portal hypertension until she suddenly developed jaundice, acholic stools, and bacteremia not responsive to a course of steroids and intravenous antibiotics. Suspecting obstruction at the site of the previously exteriorized anastomosis, a percutaneous cannulation of the conduit was performed. Catheterization of the conduit obstruction unkinked it and reestablished bile flow. She has remained anicteric with stable liver function.

Anastomosis, Roux-en-Y↗

Impaired calcium metabolism associated with hypertension in Zucker obese rats.

Recent data from our laboratory indicate that reduced membrane Ca-adenosine triphosphatase (ATPase) activity in non-insulin-dependent diabetics may be responsible for increases in intracellular calcium and, consequently, for elevated vascular resistance. Since obesity is frequently associated with hypertension, even before the development of overt diabetes, we evaluated blood pressure and erythrocyte cation levels and membrane Na/K-ATPase and Ca-ATPase in Zucker obese rats and their lean controls (n = 10 per group). Intra-arterial blood pressure, determined via a femoral cannula, demonstrated elevated systolic and diastolic pressure in the obese rats (P less than .05). There were no significant differences in Na/K-ATPase between groups, but there was a decrease in Ca-ATPase (P less than .01) in the obese rats and an increase in tissue and cellular calcium content (P less than .05). These data demonstrate a specific impairment in membrane Ca-ATPase activity in obese rats they may have caused the observed increase in cellular calcium and, consequently, increased blood pressure. These phenomena may result from impaired insulin activation of membrane Ca-ATPase in these insulin-resistant animals.

Animals↗