The heterogeneity of an influenza virus A population due to differences at individual hemagglutinin H3 sites]

Using monoclonal antibodies to hemagglutinin and nucleoprotein of various influenza virus strains, the populations of long-passaged strain A/Hong Kong/1/68 and of recently isolated strain A/sparrow/Ukraine/83 belonging to the H3N2 serovariant were shown to have subpopulations of virions differing in the structure of antigenic sites of hemagglutinin and in nucleoprotein domain which correlated with the degree of electrostatic interaction of virions with an ion-exchanger. The results of the study indicate a possibility of separation in the course of stepwise ion-exchange chromatography on DEAE-Sephadex A-50 of antigenic variants of influenza virus strains which is very important for the understanding of the mechanisms of population variability as well as for investigation of individual epitopes of hemagglutinin and nucleoprotein domains of influenza virus in evaluation of antigenic relationships of virions belonging to the same strain of a certain serotype.     

Bioavailability of Soil-Bound TCDD: Dermal Bioavailability in the Rat

Bioavailability of Soil-Bound TCDD: Dermal Bioavailability inthe Rat. SHU, H., TEITELBAUM, T., WEBB, A. S., MARPLE, L., BRUNCK,B. DEI ROSSI, D., MURRAY, J., AND PAUSTENBACH, D. (1988). Fundam.Appl. Toxicol. 10, 335-343. 2,3,7,8-Tetrachlorodibenzo-p-dioxin(TCDD), an unwanted by-product formed during the manufactureof hexachlorophene and phenoxyherbicides, has been found asan environmental contaminant in many U.S. and Western Europeansites. This study examines in the rat the degree of dermal absorptionof TCDD bound to soil. Such information would assist regulatoryagencies in evaluating the degree of exposure of humans whocome in contact with TCDD-contaminated soil. Several parameterswhich may influence dermal absorption were studied, includingTCDD dose, duration of contact, presence of crankcase oil asa co-contaminant, and environmentally contaminated vs laboratory-preparedsoil. The dermal penetration of TCDD following 4 hr of contactwith skin was approximately 60% of that following 24 hr of contact(P 0.05). Following 24 hr of contact with the skin, the degreeof dermal uptake of TCDD contaminated soil was approximately1% of the administered dose. Under the conditions of the presentstudy, the degree of uptake does not appear to be influencedto any significant extent by the concentration of TCDD on soil,the presence of crankcase oil as co-contaminants, or by environmentallyvs laboratory-contaminated soil. Although a number of parametersexamined in this study did not significantly influence the degreeof dermal absorption of TCDD in the rat following 24 hr of contactwith the contaminated soil, the unqualified use of the 1% valueto estimate human exposure would overestimate human exposure,since there is general agreement among researchers that ratskin tends to be more permeable than human skin to highly lipid-solublecompounds such as TCDD.     

Intergenerational instability of the CAG repeat of the gene for Machado- Joseph disease (MJD1) is affected by the genotype of the normal chromosome: implications for the molecular mechanisms of the instability of the CAG repeat

Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder caused by unstable expansion of a CAG repeat in the MJD1 gene at 14q32.1. To identify elements affecting the intergenerational instability of the CAG repeat, we investigated whether the CGG/GGG polymorphism at the 3' end of the CAG repeat affects intergenerational instability of the CAG repeat. The [expanded (CAG)n-CGG]/[normal (CAG)n- GGG] haplotypes were found to result in significantly greater instability of the CAG repeat compared to the [expanded (CAG)n- CGG]/[normal (CAG)n-CGG] or [expanded (CAG)nGGG]/[normal (CAG)n-GGG] haplotypes. Multiple stepwise logistic regression analysis revealed that the relative risk for a large intergenerational change in the number of CAG repeat units (< -2 or > 2) is 7.7-fold (95% CI: 2.5-23.9) higher in the case of paternal transmission than in that of maternal transmission and 7.4-fold (95% CI: 2.4-23.3) higher in the case of transmission from a parent with the [expanded (CAG)n-CGG]/[normal (CAG)n-GGG] haplotypes than in that of transmission from a parent with the [expanded (CAG)n-CGG]/[normal (CAG)n-CGG] or [expanded (CAG)n- GGG]/[normal (CAG)n-GGG] haplotypes. The combination of paternal transmission and the [expanded (CAG)n-CGG]/[normal (CAG)n-GGG] haplotypes resulted in a 75.2-fold (95% CI: 9.0-625.0) increase in the relative risk compared with that of maternal transmission and the [expanded (CAG)n-CGG]/[normal (CAG)n-CGG] or [expanded (CAG)n- GGG]/[normal (CAG)n-GGG] haplotypes. The results suggest that an inter- allelic interaction is involved in the intergenerational instability of the expanded CAG repeat.      

Chromosomal aberrations and micronucleus frequency in nurses occupationally exposed to cytotoxic drugs

In this study, we evaluated the effect of low level occupationalexposure of nurses in a medical oncology unit in Cairo, Egypt,to anticancer drugs. Twenty nurses who constantly handled thesedrugs and 20 controls, matched according to age and sex, wereexamined. Metaphase chromosomes were studied. Percentages ofmetaphases with chromosomal aberrations were significantly higher(P < 0.001) in the exposed group (6.1 ± 2.7) versusthe controls (2.6 ± 1.6). The detected chromosomal aberrationswere in the form of chromatid gaps, chromatid breaks and acentricfragments. Micronucleated peripheral blood lymphocytes werealso analyzed in cytochalasin B treated binucleated lymphocytes.There was significant increase in cells with micronuclei (P< 0.001) in nurses (10.05 ± 4.71) in comparison tothe matched control (5.42 ± 2.22) (P < 0.001). Nursesexposed to the cytotoxic drugs for     

The mouse Mid1 gene: implications for the pathogenesis of Opitz syndrome and the evolution of the mammalian pseudoautosomal region

We have recently reported isolation of the gene responsible for X- linked Opitz G/BBB syndrome, a defect of midline development. MID1 is located on the distal short arm of the human X chromosome (Xp22. 3) and encodes a novel member of the B box family of zinc finger proteins. We have now cloned the murine homolog of MID1 and performed preliminary expression studies during development. Mid1 expression in undifferentiated cells in the central nervous, gastrointestinal and urogenital systems suggests that abnormal cell proliferation may underlie the defect in midline development characteristic of Opitz syndrome. We have also found that Mid1 is located within the mouse pseudoautosomal region (PAR) in Mus musculus , while it seems to be X- specific in Mus spretus. Therefore, Mid1 is likely to be a recent acquisition of the M. musculus PAR. Genetic and FISH analyses also demonstrated a high frequency of unequal crossovers in the murine PAR, creating spontaneous deletion/duplication events involving Mid1. These data provide evidence for the first time that genetic instability of the PAR may affect functionally important genes. In addition, we show that MID1 is the first example of a gene subject to X-inactivation in man while escaping it in mouse. These data contribute to a better understanding of the molecular content and evolution of the rodent PAR.      

In vitro activity of ampicillin, cefoperazone, their combinations with sulbactam and other antimicrobials: survey of Russian isolates

Methodological differences makes it difficult to compare results of antimicrobial susceptibility testing obtained in Russia and in other regions. During the period from October 1993 to May 1994 susceptibility of 1296 isolates of bacteria was investigated according to NCCLS standards by the broth microdilution method. The order of activity of antibiotics against Gram-negative bacteria based on percent of susceptible strains from common hospitals were: amikacin (98%) > ciprofloxacin (93%) = imipenem (93%) > cefoperazone/sulbactam (92%) > ceftazidime (89%) > ceftriaxone (81%) > cefotaxime (80%) > cefoperazone (77%) > gentamicin (71%) > ampicillin/sulbactam (51%) > cefazoline (45%) > ampicillin (25%). The order of activity against strains from teaching hospitals was similar but the percent of susceptible strains was 10-20% less for the majority of antibiotics. The susceptibility level of Gram-negative isolates from Moscow teaching hospitals is lower than from Northern America and Europe. Ampicillln/sulbactam and cefoperazone/sulbactam, as well as other cephalosporins, demonstrated high activity against methicillin-susceptible staphylococci and penicillin-susceptible pneumococci. B-lactams/beta-lactamase inhibitor combinations were active against 100% strains of anaerobic bacteria.     

The no-reflow phenomenon and its clinical significance

The no-reflow phenomenon is characterized by inadequate myocardial perfusion without angiographic manifestations of mechanical vascular occlusion. The phenomenon occurs after coronary vascular interventions (coronary angiography, percutaneous coronary angioplasty, stenting, coronary artery bypass surgery). The development of the no-reflow phenomenon significantly worsens clinical evolution of disease increasing the number of cases of congestive heart failure and hospital mortality. Changes of endothelial function and morphology, changes of blood rheology and microvascular autoregulation are important for pathogenesis of the phenomenon. The treatment include intracoronary introduction of verapamil, adenosine, intravenous introduction of activators of KATP channels (nicorandil), inhibitors of glycoprotein IIb/IIIa receptors. The reasons for early preventive use of intracoronary introduction of verapamil and other drugs in the presence of risk of development of no-reflow phenomenon are presented. The interrelationship between no-reflow phenomenon and syndrome X is also stressed.     

Rheolytic thrombectomy with AngioJet catheter during transluminal coronary revascularization in patients with acute myocardial infarction

BACKGROUND: Although balloon angioplasty and stenting are effective in the treatment of acute myocardial infarction (M1), reduced coronary flow and distal embolization frequently complicate interventions when thrombus is present. Adjunctive treatment with mechanical thrombectomy devices was suggested to reduce these complications. METHODS: We evaluated immediate angiographic, in-hospital and 30-day follow-up clinical outcomes of 185 patients with acute MI and angiographically evident thrombus who were treated with AngioJet rheolytic thrombectomy followed by immediate definitive treatment. RESULTS: Procedural success (residual diameter stenosis <50% and thrombolysis in myocardial infarction [TIMI] flow >2 after final treatment) was 97%. Rheolytic thrombectomy success was achieved in 7% of patients. Subsequent definitive treatment included stenting in 67% and balloon angioplasty alone in 26% of patients. Final TIMI 3 flow was achieved in 89%. AngioJet treatment resulted in mean thrombus area reduction from 69.6 mm(2) at baseline to 17.3 mm(2) post-thrombectomy (p<0.001). Procedural complications included distal embolization (7.6%) and perforation (1.1%). Clinical success (procedure success without major in-hospital cardiac events) rate was 88%, in-hospital mortality - 7.0%. There were no further major adverse events during 30-day follow-up. CONCLUSION: Rheolytic thrombectomy can be performed safely and effectively in patients with acute MI, allowing for immediate definitive treatment of thrombus-containing lesions.