A comparison of the hypolipidemic action of probucol at doses of 500 and 1000 mg/day in moderate hyperlipoproteinemia

AIM: Evaluation of effectiveness of hypolipidemic action of probucol in doses 500 and 1000 mg/day and comparison of probucol blood concentrations on the treatment month 3 and 6. MATERIALS AND METHODS: Probucol (Akrikhin, Russia) was given to 41 patients with primary hypercholesterolemia in a dose 500 mg/day. 3 months later the patients were divided into two groups. Group 1 patients exhibited a > 10% decrease in cholesterol levels and continued to take probucol in the dose 500 mg/day. Group 2 patients were crossed over to higher cholesterol dose--up to 1000 mg/day. Lipids levels were measured by enzyme tests, apoproteins--by immunoturbidimetry and immunodiffusion, probucol concentrations--by high-performance liquid chromatography. RESULTS: After 3 months of treatment, cholesterol lowered by 14.3 and 9.2% in groups 1 and 2, respectively. After 6 months, by 19.7 and 12.9%, respectively. Probucol concentrations in blood were higher after 6 months of treatment than after 3 months in both groups. No significant differences existed between the groups by probucol concentrations in 3 and 6 months. CONCLUSION: Hypolipidemic effect of probucol depended on the individual features of lipoproteins metabolic disorders rather than the drug blood concentration. Larger probucol doses fail to reduce cholesterol further.     

Granulocytic sarcoma presented as a reactivation of chronic myeloid leukemia after allogenic marrow transplantation

The authors report the case of a chronic myeloid leukemia (CML) patient submitted to allogenic bone marrow transplantation, who had probably never entered complete remission. The disease was reactivated as a granulocytic sarcoma, next to a platinum plate installed to correct a tibia fracture 11 years earlier. Its final event was a myeloid Ph1 + blastic crisis that was unsuccessfully treated with high doses of sc interferon and citarabine.     

Crystal structure of the simian immunodeficiency virus (SIV) gp41 core: conserved helical interactions underlie the broad inhibitory activity of gp41 peptides

The gp41 subunit of the envelope protein complex from human and simian immunodeficiency viruses (HIV and SIV) mediates membrane fusion during viral entry. The crystal structure of the HIV-1 gp41 ectodomain core in its proposed fusion-active state is a six-helix bundle. Here we have reconstituted the core of the SIV gp41 ectodomain with two synthetic peptides called SIV N36 and SIV C34, which form a highly helical trimer of heterodimers. The 2.2 A resolution crystal structure of this SIV N36/C34 complex is very similar to the analogous structure in HIV-1 gp41. In both structures, three N36 helices form a central trimeric coiled coil. Three C34 helices pack in an antiparallel orientation into highly conserved, hydrophobic grooves along the surface of this coiled coil. The conserved nature of the N36-C34 interface suggests that the HIV-1 and SIV peptides are functionally interchangeable. Indeed, a heterotypic complex between HIV-1 N36 and SIV C34 peptides is highly helical and stable. Moreover, as with HIV-1 C34, the SIV C34 peptide is a potent inhibitor of HIV-1 infection. These results identify conserved packing interactions between the N and C helices of gp41 and have implications for the development of C peptide analogs with broad inhibitory activity.     

Surface topography of phytochrome A deduced from specific chemical modification with iodoacetamide

Phytochromes are a photoreversible photochromic light switch for photomorphogenesis in plants. The molecular structure and functional mechanism of phytochromes are not fully understood. On the basis of complete mapping of total tryptic digest of the iodoacetamide-modified oat phytochrome A (phyA), the molecular surface topography of phyA was probed by specific chemical modification of cysteine residues with [14C]iodoacetamide. Under native conditions, only two cysteines (Cys-158 and Cys-311) of eleven half-cystines of the N-terminal chromophore binding domain were modified to a significant extent. In the C-terminal domain, six cysteine residues (Cys-715, Cys-774, Cys-809, Cys-869, Cys-961, Cys-995) were readily accessible to iodoacetamide. Among the reactive cysteine residues, only cysteine-311 displayed reactivity that was dependent on the photochromic form (Pr left arrow over right arrow Pfr) of the photoreceptor. Surprisingly, the modification of Cys-311 in the vicinity of the chromophore attachment site (Cys-321) did not have any detectable effect on spectral properties of phyA. Most of the cysteines of the N-terminal domain (Cys-83, Cys-175, Cys-291, Cys-370, Cys-386, Cys-445, Cys-506) are deeply buried in the core of the chromophore binding domain, as they can be modified only after denaturation of the chromoprotein. In the C-terminal domain, modification of only one cysteine residue (Cys-939) required protein denaturation. Since all 22 half-cystines can be modified with iodoacetamide without reduction of the chromoprotein, it follows that oat phyA does not have any disulfide bonds. We found that Cys-311, Cys-774, Cys-961, and Cys-995 could be easily partially oxidized under the conditions used for phytochrome isolation. The surface topography/conformation of oat phyA and its role in protein-protein recognition in phytochrome-mediated signal transduction are discussed in terms of the relative reactivity of cysteine residues.     

Genotypic basis of low viability in vestigial mutants of Drosophila melanogaster

The role of a marker mutation and other genes in a decrease in viability was studied in the Drosophila melanogaster vg line. In flies of the C-S line, chromosome 2 was substituted by the homologous chromosome of the vg flies. In addition, the flies of the mutant phenotype with mutant genes partially or completely substituted by the wild-type C-S genes were obtained in saturating crosses C-S x vg. In the reciprocal variant of chromosome 2 substitution, the flies of the C-S phenotype with chromosomes 1, 3, and 4 from the vg line were obtained. Chromosome 2 of the vg line, introduced into C-S fly karyotype, proved to substantially reduce the heat resistance and life span of flies. In the case of reciprocal replacement (C-S line chromosome 2 substituted for the homologous chromosome of vg flies), a significant increase in viability was observed, which, however, never reached the level characteristic of the C-S line. As the vg genotype became saturated with C-S genes, the heat resistance and life span of flies increased substantially. However, even the complete saturation of mutant chromosomes with wild-type genes never resulted in the equal viability of vg and C-S flies. These data suggest that the low viability of the vg mutant is largely accounted for by the gene composition of the second chromosome and, primarily, by the presence of the vg gene. Nevertheless, there is evidence that, along with the pleiotropic effect of the marker mutation, other genes not linked to chromosome 2 are responsible for the studied physiological properties of the vg flies.     

Further evidence for elevated human minisatellite mutation rate in Belarus eight years after the Chernobyl accident

Analysis of germline mutation rate at human minisatellites among children born in areas of the Mogilev district of Belarus heavily polluted after the Chernobyl accident has been extended, both by recruiting more families from the affected region and by using five additional minisatellite probes, including multi-locus probe 33.6 and four hypervariable single-locus probes. These additional data confirmed a twofold higher mutation rate in exposed families compared with non-irradiated families from the United Kingdom. An elevated rate was seen at all three independent sets of minisatellites (detected separately by multi-locus probes 33.15, 33.6 and six single-locus probes), indicating a generalised increase in minisatellite germline mutation rate in the Belarus families. Within the Belarus cohort, mutation rate was significantly greater in families with higher parental radiation dose estimated for chronic external and internal exposure to caesium-137, consistent with radiation induction of germline mutation. The spectra of mutation seen in the unexposed and exposed families were indistinguishable, suggesting that increased mutation observed over multiple loci arises indirectly by some mechanism that enhances spontaneous minisatellite mutation.     

Acute appendicitis complicated by destruction of the large intestine and septic shock

Access and visualization in the implant-abutment area are often compromised. Tissue impingement and lack of abutment position verification may result in inaccurate fit.     

Renin localization in segmental renal hypoplasia. Immunohistochemical demonstration in two cases

The distribution of renin in two cases of segmental renal hypoplasia was investigated by immunofluorescence and the peroxidase anti-peroxidase (PAP) method using an anti-human renin antiserum. Renin-containing cells were found only in hypoplasic segments in the vicinity of altered glomeruli and small arteries. Well-preserved renal cortex and areas of chronic atrophic pyelonephritis failed to show any demonstrable site of renin production. Whatever is the mechanism of the disease, the characterization of large numbers of renin-containing cells in the affected kidney support a role for the renin-angiotensin system stimulation in this form of hypertension.