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Biomedical subjects

R Gutman

Publications and source records attributed to R Gutman.

At least 55 records · Page 3Linked to original sources
PubMed1984

Inhibition of growth of human or hamster pancreatic cancer cell lines by alpha-difluoromethylornithine alone and combined with cis-diamminedichloroplatinum(II).

A major problem in the therapy of pancreatic adenocarcinoma is its inherent resistance to most chemotherapeutic agents. Previously, we have reported that the four pancreatic cancer cell lines studied here have elevated levels of ornithine decarboxylase, a growth-regulating enzyme, and further that the degree of elevation tends to parallel the degree of chemoresistance. On the basis of these prior findings, we investigated the effects of alpha-difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase, alone and in combination with cis-diamminedichloroplatinum(II) (cisplatin), to which two of the four cell lines display relative resistance. The cell lines studied were: two of human origin, PANC-1 and COLO-357; and two of hamster origin, WD PaCa and PD PaCa. Colony formation (clonogenic) assays were used to evaluate drug effects. Cells were exposed continuously to DFMO in medium. For the combined treatments, cells were exposed to cisplatin for 1 hr, washed, and then plated in DFMO-containing medium. The inhibitory effects of DFMO were predominantly cytostatic, were reversible by putrescine, and were roughly additive when combined with cisplatin. Our panel of cell lines responded heterogeneously to DFMO, with PANC-1 and WD PaCa showing the most sensitivity. The combination of DFMO and cisplatin appears to be a promising experimental approach to overcoming drug resistance in pancreatic cancer.

Animals↗
PubMed1983

Effect of sucrose diet on insulin secretion in vivo and in vitro and on triglyceride storage and mobilisation of the heart of rats.

Basal heart triacylglycerol (TG) (mumole triacylglycerol/g of dry weight) (- before "in vitro" Langendorff perfusion -) was significantly higher in animals rendered chronically hypertriglyceridaemic (H) by a 63% sucrose-rich diet than in controls (C, standard diet); 28 +/- 2.6 means + SEM vs. 19.3 +/- 1.2; respectively (p less than 0.01). After 40' perfusion with Krebs-Henseleit buffer + 5.5 mM glucose, 2.5 mM Ca++, TG content fell to 14.2 +/- 0.6 in C and 14.9 +/- 1.9 in H (n.S.). Administration of 1 n mol x min-1 of glucagon (Gn) from min 20 to 40 reduced TG to 9.0 +/- 0.5 in C (p less than 0.05). In contrast no effect of Gn was observed in H (TG at min 40: 16.7 +/- 2.5). Glycogen (Gly) content (mumol/g of dry weight) after Gn perfusion fell from 30 +/- 1.9 to 17 +/- 2.1 (p less than 0.01) in C, while again no effect was recorded in H. "In vivo" plasma glucose fractional coefficient disappearance rate was lower (p less than 0.001) in H: 1.01 x 10(-2) +/- 0.09 x 10(-2) vs 2.61 x 10(-2) +/- 0.14 x 10(-2) in C, in spite of H showing hyperinsulin secretion. Hyperinsulinism was further documented by "in vitro" Iri release studies from incubated pancreas pieces. In the absence of glucose (G) from the incubation medium H produced 541 +/- 19.8 mU/mg weight Tissue/20', while C produced 91.2 +/- 12.7 (p less than 0.001). With 100 mg% G, H released 1058 +/- 259 and C 377 +/- 82.5 (p less than 0.001). It is suggested that hyperinsulin secretion plus insulin resistance may account for the above findings.

Animals↗
PubMed1983

Post-heparin plasma hepatic triglyceride lipase and monoglyceride hydrolase activities in hyperlipemia induced by a sucrose rich diet.

We have previously reported that normal Wistar rats fed an isocaloric, sucrose-rich (63%) diet (SRD) developed glucose intolerance and elevated triglyceride levels in plasma as well as in heart and liver tissue. This metabolic state was accompanied by hyperinsulinism both in vivo and in vitro, suggesting that a state of insulin resistance has developed. The aim of this study was to gather information on the various plasma post-heparin lipolytic activities in rats fed a SRD. Hepatic triglyceride lipase (H-TGL) was evaluated by both, protamine sulfate inhibition (PSI) of extrahepatic lipoprotein lipase (LPL) and heparin-Sepharose affinity chromatography (H-SAC). Both methods rendered comparable results. Total triglyceride lipase (T-TGL) was measured after Krauss et al. and monoglyceride hydrolase (MGH) after Vogel et al. Our results have shown a significant decline of plasma T-TGL (5.32 +/- 0.34 means +/- SEM vs. 7.48 +/- 0.64 mumol glycerol ml-1 h-1; p less than 0.01), H-TGL (3.71 +/- 0.28 vs. 5.05 +/- 0.69; p less than 0.05), LPL (1.61 +/- 0.26 vs. 2.42 +/- 0.41; p less than 0.05) and MGH (558 +/- 108 mumol glycerol l-1 min-1 vs. 1,165 +/- 45; p less than 0.001) activities. Thus, feeding a sucrose-rich diet induced a state of hyperlipemia and insulin resistance in which not only plasma T-TGL but also H-TGL and MGH activities were significantly decreased. This suggests that the latter two enzymes are also under nutritional and/or hormonal control.

Animals↗
PubMed1982

Chemotherapy of pancreatic adenocarcinoma: initial report on two transplantable models in the Syrian hamster.

Experimental evaluation of chemotherapy of pancreatic cancer has been limited by the lack of suitable animal models, which have only recently become available. The present study is the first report on the chemosensitivity of two transplantable animal models of pancreatic adenocarcinoma. The single-agent antitumor activity of 5-fluorouracil, cyclophosphamide, mitomycin C (MMC), methotrexate, actinomycin D, vincristine, and two dose levels of Adriamycin (ADR) were tested against established palpable tumors of well-differentiated pancreatic ductal adenocarcinoma (WD PaCa), a solid tumor model of the Syrian hamster. None of the agents or dosages of ADR were effective against palpable WD PaCa tumors. ADR, MMC, streptozotocin, and the combination of 5-fluorouracil, ADR, and MMC were similarly ineffective when administered 1 week after WD PaCA implantation, while tumors were still nonpalpable. The behavior of poorly differentiated pancreatic ductal adenocarcinoma (PD PaCa), an ascitic model of the Syrian hamster, was studied for comparison. In vivo, with survival as the end point, PD PaCa is markedly sensitive to ADR, perhaps weakly sensitive to MMC, and resistant to streptozotocin. In vitro clonogenic assays from cultured PD PaCa and WD PaCa confirmed the pattern of response seen in vivo. The data suggest that these recently developed pancreatic cancer models can be profitably used and compared, both in vivo and in vitro, as examples of relatively chemotherapy resistant (WD PaCa) and more sensitive (PD PaCa) tumor models.

Adenocarcinoma↗
PubMed1981

An outbreak (?) caused by Escherichia coli O126:K71:H5 in premature infants.

The strain E. coli O126:K71:H5 was recovered during a 6 week period, from stool samples of 13 premature infants hospitalized in the Premature Infants Nursery Unit. Of a total of 147 tested stool samples, 69 were positive. This strain was also recovered for a long period from the respiratory tract of one of the infants. The strain had a low virulence for the infants. No clear relationship could be demonstrated between clinical status and recovery of the strain. The strain did not possess any of the well defined pathogenic mechanisms, namely enterotoxins LT and ST, and invasiveness. The production of a thermolabile substance toxic for Vero cells was demonstrated. The strain possessed both guinea pig mannose-sensitive and human mannose resistant hemagglutinins. In spite of the production of thermolabile toxic substance for Vero cells and in spite of its contagiousness and intestinal tract colonization capacity, the strain displayed the characteristics of an opportunistic pathogen rather than classic EPEC.

Animals↗
PubMed1976

Reevaluation of the polyvinylpyrrolidone sedimentation test in the diagnosis of ABO hemolytic disease of the newborn.

The rate of cord erythrocytes sedimentation in 1.5% polyvinylpyrrolidone (PVP) solution was investigated. Of 70 infants showing accelerated sedimentation rate, 49 had signs of hemolytic disease. Rh incompatibility did not affect the sedimentation rate. Infectious diseases might cause a slight increase in the rate of sedimentation. The test was found to be very sensitive. It could detect ABO incompatibilities even in absence of marked bilirubinemia. Furthermore, positive identification of incompatibilities were obtained in ABO-HDN cases where both direct and indirect Coombs tests were negative. High correlation was noted between anti A and B titer of maternal sera and the accelerated sedimentation of newborn red blood cells. The erythrocytes sedimentation test in PVP (PVP-ESR test) is recommended for the early detection of cases in which the red cells are affected by IgG anti-A or anit-B.

ABO Blood-Group System↗
PubMed1970

Studies on the biological activity of porcine proinsulin.

The biological activity of purified porcine proinsulin was investigated in rats. In vivo studies revealed that proinsulin produced a hypoglycemic response similar to insulin but of lesser magnitude. Hypophysectomized and adrenalectomized animals proved to be more sensitive to proinsulin than normal. In vitro studies with rat hemidiaphragm were consistent with the in vivo findings. No competition with insulin action could be demonstrated. Experiments were carried out to determine whether proinsulin is converted to intermediate forms or insulin as a requisite to its biological activity. Labeled proinsulin injected in vivo or incubated in vitro remained intact by a variety of techniques (Sephadex column chromatography and polyacrylamide-gel electrophoresis). An inhibitory action of Kunitz pancreatic trypsin inhibitor on proinsulin action in vitro was confirmed. No clarification of this effect could be ascertained.

Adrenal Glands↗
PubMedDate not supplied

Lung abscess caused by Streptococcus pneumoniae type 3. The importance of counterimmunoelectrophoresis in laboratory diagnosis.

We are reporting the case of an 18-month-old girl with a post-pneumonic lung abscess. The counterimmunoelectrophoresis (CIE) of the patient's urine during the bacteremic phase of the disease gave a precipitation line with pneumococcal antiserum. Later in the course of the disease, after the diagnosis of lung abscess had been established, the pus drained from the abscess gave positive reactions with pneumococcal omnivalent serum and type 3 pneumococcal antiserum. At this stage, the pus was sterile and blood cultures were negative. This case demonstrates that the CIE test is a simple procedure which gives a rapid and exact diagnosis up to the serotype level.

Counterimmunoelectrophoresis↗