Effects of benfluorex metabolites on membrane fluidity and insulin-related processes

Hepatocyte growth factor (HGF) is a potent mitogen for the maturation of hepatocytes in vitro which plays a role in liver regeneration in vivo. In addition, transforming growth factor-beta 1 (TGF-beta 1) is also a potent regulator of liver regeneration. In attempting to clarify the mechanisms related to liver regeneration after partial hepatectomy, we investigated the expression of HGF and TGF-beta 1 in rats with liver cirrhosis (LC). A rat model of LC was prepared using carbon tetrachloride (CCl4). The expression of HGF mRNA in both the LC and control groups showed a similar time-course with the highest expression seen at 18h after a 70% hepatectomy. The expression of TGF-beta 1 mRNA peaked at 18h after partial hepatectomy in the LC group and at 48h in the control group. The 5-bromo-2'-deoxyuridine (BrdU) labeling index for the LC group at 24, 48, and 72 h after partial hepatectomy was 9.2%, 5.9%, and 1.8%, while for the control group it was 7.0%, 11.7%, and 6.8%, respectively. The BrdU labeling index in the LC group was thus suppressed earlier than that in the control group. We therefore postulate that regeneration of the remnant liver in the presence of LC accelerates immediately after partial hepatectomy, but the extent of regeneration is insufficient because of an early cessation due to an early expression of TGF-beta 1.     

Analytical modeling of imperfect bond between coated fibers and matrix material

The present study is intended to find the stress intensity factors (SIF) and strain energy release rates (SERR) at the tips of an interface crack in a non-homogeneous medium. The boundary-value problem governing a three-phase concentric cylinders model is used to analyze annular interfacial crack problems with Love's strain functions. The complex form of a singular integral equation of second kind is formulated using Bessel's functions in Fourier domain. Stress intensity factors (SIF) and total strain energy release rates (SERR) are calculated using Jacoby polynomials. For validity of the equations of Stress Intensity Factors, the Singular Integral Equation (SIE) of a three concentric cylinders model is reduced to the SIE for a two concentric cylinders model and results are compared with previous results of Erdogan.     

Human granulocytes contain an opiate alkaloid-selective receptor mediating inhibition of cytokine-induced activation and chemotaxis

Human peripheral blood granulocytes previously were found to contain opioid delta 2-receptors mediating stimulation by opioid peptides of chemotaxis. Studies presented in this work indicate that granulocytes also contain opiate alkaloid-selective, opioid peptide-insensitive receptors mediating inhibition by morphine and other opiates of cytokine-induced activation and chemotaxis. Binding studies with [3H]morphine and [3H]diprenorphine ([3H]DPN) indicated the presence of receptor sites, at considerable density with affinities and selectivity for opiates comparable with those of the mu 3-receptor of human peripheral blood monocytes (macrophages). The influence of the guanosine 5'-triphosphate (GTP) analogue GppNHp on binding indicated that the granulocyte receptor was linked to a G protein. Morphine but not opioid peptides interfered with activation and/or chemotaxis of the granulocytes induced by TNF-alpha, IL-1 alpha, IL-8, and FMLP (chemotactic peptide). These effects of morphine were blocked by the antagonist naloxone. Levorphanol inhibited TNF-alpha-induced activation, and also potentiated the inhibition by morphine. Furthermore, in binding assays, levorphanol enhanced the affinity of the receptor for morphine. Dextrorphan had no effect on activation or chemotaxis, and it also had no effect on binding, indicative of stereoselectivity for the effect of levorphanol. It is concluded that human granulocytes contain opiate alkaloid-selective mu 3-receptors that mediate inhibitory effects of morphine on cellular activation by cytokines.     

Effects of passive tilt and submaximal exercise on spectral heart rate variability in ventricular fibrillation patients without significant structural heart disease

It has been shown that tilt and exercise elicit significant changes in autonomic activity in normal subjects and that submaximal exercise causes a greater reduction in heart rate variability (HRV) in animals susceptible to ventricular fibrillation (VF). Whether there is an abnormal HRV response to tilt and exercise in patients at risk of sudden cardiac death (SCD) remains unknown. Short-term HRV before and during passive tilt and exercise was studied in 12 survivors of out-of-hospital cardiac arrest with documented VF and compared with 12 age- and sex-matched normal controls. No patient had significant structural heart disease or left ventricular dysfunction. HRV was computed as total-frequency (TF, 0.01 to 1.00 Hz), low-frequency (LF, 0.04 to 0.15 Hz) and high-frequency (HF, 0.15 to 0.40 Hz) components. There was no significant difference between normal controls and SCD survivors in HRV before or during tilt or submaximal exercise testing. The HF component was significantly decreased during tilt compared with that in the supine position in both normal controls (5.85 +/- 0.61 vs 5.08 +/- 0.95 In(msec2), p = 0.005) and patients (5.58 +/- 1.49 versus 4.74 +/- 1.18 In(msec2), p = 0.003). There was again no significant change in the TF or LF components during tilt in either patients or controls. All frequency components were significantly decreased during submaximal exercise testing in both patients and controls. However, there was no significant difference in any of these tilt- and exercise-induced changes in HRV between normal controls and SCD survivors.(ABSTRACT TRUNCATED AT 250 WORDS)     

Current distribution, resistance, and inductance forsuperconducting strip transmission lines

A method for the calculation of the current distribution, resistance, and inductance matrices for a system of coupled superconducting transmission lines having finite rectangular cross-section is presented. These calculations allow accurate characterization of both high-T_c and low-T _c superconducting strip transmission lines. For a single stripline geometry with finite ground planes, the current distribution, resistance, inductance, and kinetic inductance are calculated as functions of the penetration depth for various film thicknesses. These calculations are then used to determine the penetration depth for Nb, NbN, and YBa₂Cu₃O_7-x superconducting thin films from the measured temperature dependence of the resonant frequency of a stripline resonator. The calculations are also used to convert measured temperature dependence of the quality factor to the intrinsic surface resistance as a function of temperature for an Nb stripline resonator     

Maximum power density for an endoreversible carnot heat engine

An analysis using maximum power-density criteria has been carried out for an endoreversible Carnot heat engine. The results have been compared with known results on maximum power analysis. The design parameters at maximum power density lead to smaller and more efficient endoreversible Carnot heat engines than those working at maximum power output.     

The genotype of the human cancer cell: implications for risk analysis

An extremely large database describes genotypes associated with the human cancer phenotype and genotypes of human populations with genetic predisposition to cancer. Aspects of this database are examined from the perspective of risk analysis, and the following conclusions and hypotheses are proposed: (1) The genotypes of human cancer cells are characterized by multiple mutated genes. Each type of cancer is characterized by a set of mutated genes, a subset from a total of more than 80 genes, that varies between tissue types and between different tumors from the same tissue. No single cancer-associated gene nor carcinogenic pathway appears suitable as an overall indicator whose induction serves as a quantitative marker for risk analysis. (2) Genetic defects that predispose human populations to cancer are numerous and diverse, and provide a model for associating cancer rates with induced genetic changes. As these syndromes contribute significantly to the overall cancer rate, risk analysis should include an estimation of the effect of putative carcinogens on individuals with genetic predisposition. (3) Gene activation and inactivation events are observed in the cancer genotype at different frequencies, and the potency of carcinogens to induce these events varies significantly. There is a paradox between the observed frequency for induction of single mutational events in test systems and the frequency of multiple events in a single cancer cell, suggesting events are not independent. Quantitative prediction of cancer risk will depend on identifying rate-limiting events in carcinogenesis. Hyperproliferation and hypermutation may be such events. (4) Four sets of data suggest that hypermutation may be an important carcinogenic process. Current mechanisms of risk analysis do not properly evaluate the potency of putative carcinogens to induce the hypermutable state or to increase mutation in hypermutable cells. (5) High-dose exposure to carcinogens in model systems changes patterns of gene expression and may induce protective effects through delay in cell progression and other processes that affect mutagenesis and toxicity. Paradigms in risk analysis that require extrapolation over wide ranges of exposure levels may be flawed mechanistically and may underestimate carcinogenic effects of test agents at environmental levels. Characteristics of the human cancer genotype suggest that approaches to risk analysis must be broadened to consider the multiplicity of carcinogenic pathways and the relative roles of hyperproliferation and hypermutation. Further, estimation of risk to general human populations must consider effects on hypersusceptible individuals. The extrapolation of effects over wide exposure levels is an imprecise process.     

Juvenile chronic arthritis: a cephalometric analysis of the facial skeleton

A retrospective cross-sectional cephalometric investigation was undertaken to examine the facial form of a group of Finnish children with juvenile chronic arthritis (JCA). Following digitization, the radiographs were divided into three age groups, and according to whether or not 'bird-face' deformity was present. From a total of 67 cases (39 females and 28 males) 19 per cent were judged to be 'affected'. Analyses were carried out and the groups compared using t-tests. The mandible was found to be smaller both in ramal height and body length in the affected sample, with reduction in posterior face height being only partly compensated by increase in bony apposition at the angle producing antegonial notching. There was posterior rotation of the mandible with a reduction in angles S-N-B and S-N-Pog, and an increase in the gonial angle, the angle between the mandibular plane and S-N, maxillary, and occlusal planes. The changes in the maxilla were less marked. Although S-N-A was reduced in all three age groups, it was not significantly so. Maxillary length (ANS-PNS) was significantly smaller in the two younger age groups. In the vertical plane maxillary dimensions were reduced in the two younger age groups. A highly significant increase in the occlusal to maxillary planes angle was observed in all groups. There was, however, no difference in S-N to maxillary planes angle, indicating a more steeply inclined occlusal plane due to subnormally erupted maxillary molars. Although the inter-incisal angle was reduced there was no significant difference in the incisor inclinations in relation to the jaws and despite the posterior rotation of the mandible there was no significant increase in size of overjet or in the frequency of anterior open bite.