Alpha-melanocyte-stimulating hormone reduces endotoxin-induced liver inflammation.

Alpha-Melanocyte-stimulating hormone (MSH) is a potent anti-inflammatory agent in many models of inflammation, suggesting that it inhibits a critical step common to different forms of inflammation. We showed previously that alpha-MSH inhibits nitric oxide (NO) production in cultured macro-phages. To determine how alpha-MSH acts in vivo, we induced acute hepatic inflammation by administering endotoxin (LPS) to mice pretreated with Corynebacterium parvum, alpha-MSH prevented liver inflammation even when given 30 min after LPS administration. To determine the mechanisms of action of alpha-MSH, we tested its influence on NO, infiltrating inflammatory cells, cytokines, and chemokines. Alpha-MSH inhibited systemic NO production, hepatic neutrophil infiltration, and increased hepatic mRNA abundance for TNF alpha, and the neutrophil and monocyte chemokines (KC/IL-8 and MCP-1). We conclude that alpha-MSH prevents LPS-induced hepatic inflammation by inhibiting production of chemoattractant chemokines which then modulate infiltration of inflammatory cells. Thus, alpha-MSH has an effect very early in the inflammatory cascade.     

Guillain-Barré syndrome in South-West Stockholm, 1973–1991, 3. Clinicoepidemiological subgroups

Using hierarchical cluster analysis, applied to 47 cases of Guillain-Barre Syndrome (GBS) incident in South-West Stockholm (SWS) during the period from January 1973 to June 1992, we identified three major clinicoepidemiological subgroups. The first subgroup, 25.5% of the cases (26.7 ± 6.7 years), recorded a peak incidence at ages 20–29 years and presented significant differences from other subgroups, a high proportion of cases with onset at low age preceded by respiratory infection (83.3%) and with normal motor conduction velocity (50.0%). Also found, were less affected biological parameters, a rapidly progressive course and independence in gait at one month after onset. A second subgroup, 27.7% of cases, was severely affected, clinically and functionally. It consisted predominantly of young individuals (22.7 ± 11.1 years), with a high incidence (69.2% of cases) in autumn. A third subgroup, comprising 40.47; of cases, was older (61.1 ± 11.0 years) and, in general, also severely affected. The incidence of this form appeared to be invariant with time.     

The effect of oxygen free radicals on calcium current and dihydropyridine binding sites in guinea-pig ventricular myocytes.

1. We used electrophysiological and binding techniques to determine the effects of oxygen free radicals (OFRs) generated by dihydroxyfumaric acid (DHF, 5 mM) on calcium current and dihydropyridine binding sites in guinea-pig isolated ventricular myocytes. 2. Binding of [3H]-PN200-110 to isolated ventricular myocytes revealed one population of binding sites with a KD of 0.11 +/- 0.01 nM and Bmax of 139.1 +/- 6.9 fmol mg-1 protein (n = 24). After 15 min of exposure to DHF, the density, but not the affinity of [3H]-PN200-110 binding sites was significantly (P < 0.01) reduced to 35% of the control value (Bmax = 49.4 +/- 3.7 fmol mg-1 protein, KD = 0.11 +/- 0.01 nM, n = 15). In the presence of superoxide dismutase (SOD) and catalase (CAT) the reduction in [3H]-PN200-110 binding sites was almost completely prevented (Bmax = 120.5 +/- 7.4 in control, n = 4 and 98.8 +/- 7.4 fmol mg-1 protein in DHF plus SOD and CAT, n = 4). KD values were not modified (0.08 +/- 0.01 in control and 0.09 +/- 0.01 nM in DHF plus SOD and CAT). 3. The time-course of the reduction of [3H]-PN200-110 binding sites by OFRs was paralleled by the decrease in L-type calcium current (Ica,L) measured in patch-clamped guinea-pig ventricular myocytes either in the absence or in the presence of EGTA in the patch pipette. In the former conditions OFRs induced the appearance of calcium-dependent alterations, i.e. the transient inward current, within 10 min. After 30 min of incubation with DHF, [3H]-PN200-110 binding sites were reduced to 25% of the control value. 4. In myocytes incubated with the antilipoperoxidant agent, butylated hydroxytoluene (BHT, 50 microM), the decrease in [3H]-PN200-110 binding sites caused by DHF was partially prevented (Bmax values after 30 min exposure to DHF were 55.5 +/- 1.9 and 23.7 +/- 5.9 fmol mg-1 protein in the presence and in the absence of BHT respectively, P < 0.05). BHT did not affect the decrease in [3H]-PN200-110 binding sites during the first 15 min of exposure to DHF, but was able to prevent completely the further decrease occurring during the following 15 min of incubation with OFRs. 5. Our results demonstrate that the OFR-induced decrease in calcium current is associated with a reduction in DHP binding sites. The decrease in calcium current and in calcium channels may be implicated in the mechanical dysfunction associated with oxidative stress.     

A multicentre assessment of the specificity of ten anti-HBc screening tests

SUMMARY. Samples from 1828 donations were screened for anti-HBc at seven sites in the UK using kits supplied by 10 manufacturers. Only 10 (0.55%) donations were considered to have true anti-HBc reactivity and these were detected by all 10 kits. Additional markers of HBV infection were found in nine of these 10 donations. Additional reactives were found by all kits, the number ranging from 1 to 43.
In the four more specific kits, the 10 true reactives were clearly distinguished from the 'false reactives' by the strength of the reaction. It is concluded that the reliance on a single ELISA test for anti-HBc diagnosis is unwise. The use of a second test known to be more specific than the screening ELISA is recommended.     

The HGAR1 familial hypercholesterolemia pedigree

Data on 232 members of a single pedigree, descended from two pairs of original parents, were made available to the participants of Genetic Analysis Workshop 8 (GAW8). In addition to information concerning age and sex, measurements for 10 quantitative traits and genotypes at 22 polymorphic marker loci were also provided for a subset of 193 of these family members. © 1993 Wiley-Liss, Inc.