A cooperative study on concomitant with low-dose divided administration of cisplatin (CDDP) and sustained drip infusion of 5-fluorouracil (5-FU) for unresectable advanced gastric cancer. Osaka Cisplatin Gastric Cancer Study Group

British Indian Asian men aged <40 years have a twofold to threefold increased risk of death from coronary heart disease (CHD) compared with British whites. Epidemiological studies have suggested an association between glucose intolerance and hyperinsulinemia with premature CHD in Indian Asians. We tested the association of insulin action with myocardial infarction (MI) by using the hyperinsulinemic-euglycemic clamp in 17 MI patients: 8 Punjabi Sikhs (PSMIs), 9 British whites (BWMIs), and 17 control subjects (9 PSCs and 8 BWCs). Metabolic factors associated with insulin resistance were investigated in 51 MI patients (24 PSMIs and 27 BWMIs) and 53 control subjects (28 PSCs and 25 BWCs). Familial aggregation of defective insulin action was examined by studying five pedigrees of Sikh survivors of MI. Sikh survivors of premature MI demonstrated impaired insulin-mediated glucose uptake (P<.001) by use of the clamp technique and nonesterified fatty acid (NEFA) suppression (P<.05) by using both clamp techniques and the oral glucose tolerance test, as compared with Sikh control subjects. White patients had impaired insulin-mediated glucose uptake but normal NEFA suppression. Metabolic factors usually associated with insulin resistance, including increased 2-hour post-oral glucose tolerance test triglycerides, smaller low density lipoprotein particle size, and increased plasminogen activator inhibitor-1, were present in white (all P<.05) but surprisingly absent in Sikh (all P>.05) MI patients compared with respective ethnic control subjects. Fasting glucose and total cholesterol levels did not differ between patients and control subjects. Abdominal obesity, impaired NEFA suppression after oral glucose, and fasting hyperinsulinemia were present in Sikh MI patients and their nondiabetic first-degree relatives compared with Sikh control subjects. PS survivors of premature MI demonstrated impaired insulin-mediated glucose disposal and NEFA suppression compared with ethnic control subjects. BWMI patients showed abnormalities of carbohydrate, but not of NEFA, metabolism compared with white control subjects. Defects of insulin action manifested as abdominal obesity, impaired NEFA suppression, and fasting hyperinsulinemia are present in Sikh MI patients and their asymptomatic, nondiabetic, first-degree relatives. We suggest that these defects may be early metabolic markers that predict risk of premature MI among PSs.     

Polymer chains in semidilute solutions confined to a square channel: mean-field Gaussian chain theory and comparison with simulation results

We extend the mean-field Gaussian chain theory, originally developed for non-dilute solutions of athermal polymer chains in a slit, to solutions in a channel with a square cross section. The formulation allows one to calculate the monomer density profile, the chemical potential of the confined polymer chain, and therefore the partition coefficient. For the mean-field potential, we used the first-order approximation that neglects local monomer density fluctuations and the second-order approximation that takes into account the fluctuations. The results of the density profile and the partition coefficient were compared with those obtained in the lattice Monte Carlo simulations. The theoretical results obtained with the first-order approximation agreed well with the simulation results for chains of 100 beads below the average monomer density of ca. 0.2. At higher concentrations, the second-order results gave a better agreement. This cross over indicates a change in the interactions between polymer chains from those in one-dimension to those in three-dimensions as the correlation length in the confined solution becomes sufficiently shorter than the channel width.     

Circulating proinsulin levels in insulin-dependent diabetic patients after whole pancreas-kidney transplantation

Disproportional hyperproinsulinemia is a sensitive marker for beta-cell dysfunction. The objective of this study was to assess the proinsulin profile in persons with insulin-dependent diabetes mellitus (IDDM) after pancreas-kidney transplantation. We determined serum insulin, C-peptide, and proinsulin concentrations during an oral glucose challenge in five pancreas-kidney transplant recipients, nine nondiabetic kidney transplant recipients, and 17 normal subjects. Basal proinsulin concentrations were significantly increased in pancreas-kidney recipients (geometric mean [+/-1 SE range], 6.0 [5.5 to 6.4] pmol/L) and kidney recipients (6.4 [5.4 to 7.5] pmol/L) compared with the normal subjects (2.8 [2.5 to 3.2] pmol/L). Integrated proinsulin concentrations during the oral glucose load were also higher in pancreas-kidney recipients (1.4 [1.1 to 1.8] nmol/L x min) and kidney recipients (1.5 [1.2 to 2.0] nmol/L x min) versus normal subjects (0.8 [0.7 to 0.9] nmol/L x min). There was no difference in basal or integrated proinsulin concentrations between the two transplant groups. Even after adjustment for the glomerular filtration rate (GFR), basal and incremental proinsulin concentrations continued to be higher in the transplant groups than in the normal subjects. Proinsulin to C-peptide molar ratios both before and after the glucose load were similar in the three groups. From these findings, we conclude that pancreas-kidney transplantation provokes proportional hyperproinsulinemia, which is closely associated with its reduced clearance in the kidneys.     

Development of a sensitive ELISA for human leptin, using monoclonal antibodies

A new, sensitive ELISA for human leptin in plasma and cerebrospinal fluid (CSF) was developed, using monoclonal antibodies. The lower limit of detection of this ELISA was 0.78 pg/assay. Both intra- and interassay imprecision values were <7%. The dilution curves of plasma and CSF showed good linearity, and the recovery was 83.2-95.6%. There was good correlation between plasma leptin concentrations by the ELISA and a commercially available RIA (r = 0.99). Our ELISA is advantageous because it does not require radioisotopes, it produces results in hours rather than days, and more importantly, it improves on the detection limit and plasma interference of the RIA kit. The new ELISA enables measurement of low concentrations of leptin, as are seen in CSF and in plasma of patients with anorexia nervosa.     

Changes in mixing states of styrene–butadiene copolymer rubber and general-purpose polystyrene resin mill blend by heat treatment

The effect of heat treatment in the so-called phase inversion region was studied using uncured mill blends of various commercial styrene—butadiene copolymer rubbers (styrene content, 23.5 to 48 wt-%; styrene block, 0 to 18 wt-%) with general-purpose polystyrene resin (blend ratio, 80–40: 20–60, in wt-%). It was found that the effect of heat treatment on the hardening or softening phenomenon of blends is different in the random type from that in the block-type styrene—butadiene copolymer rubber. A thorough discussion led us to conclude that this difference is caused by the strong interaction between the polystyrene block of the copolymer and the styrene homopolymer of general-purpose polystyrene resin.     

Preparation of narrow-distribution polyvinylpyrrolidone by multi-stage high osmotic pressure chromatography

Separation of polyvinylpyrrolidone, a water-soluble polymer of neutral charge, by high osmotic pressure chromatography (HOPC) is presented. HOPC, suitable for preparative separation of polymer by molecular weight, has been applied to various organic-soluble polymers. We demonstrate here that HOPC can also separate water-soluble polymers and is capable of separating fractions of narrower polydispersity compared to preparative gel permeation chromatography (GPC). Typically fractions with a polydispersity index (PDI) of 1.4–2 were generated from broad-distribution polymers (PDI5) in significant quantities from a single separation. By multi-stage separation, standard-grade fractions were obtained. Single- and multi-pass fractions were characterized by both GPC with narrow-standard calibration and GPC in tandem with a multi-angle laser light scattering detector.