Role for interleukin-1 (IL-1) in benzene-induced hematotoxicity: inhibition of conversion of pre-IL-1 alpha to mature cytokine in murine macrophages by hydroquinone and prevention of benzene-induced hematotoxicity in mice by IL-1 alpha

Chronic exposure of humans to benzene (BZ), a myelotoxin, causes aplastic anemia and acute leukemia. The stromal macrophage that produces interleukin-1 (IL-1), a cytokine essential for hematopoiesis, is a target of BZ's toxicity. Monocyte dysfunction and decreased IL-1 production have been shown to be involved in aplastic anemia in humans. Hydroquinone (HQ), a toxic bone marrow (BM) metabolite of BZ, causes time- and concentration-dependent inhibition of processing of the 34-Kd pre-interleukin-1 alpha (IL-1 alpha) to the 17-Kd mature cytokine in murine P388D1 macrophages and BM stromal macrophages, as measured by Western immunoblots of cell lysate proteins using a polyclonal rabbit antimurine IL-1 alpha antibody. HQ over a 10-fold concentration range had no effect on the lipopolysaccharide (LPS)-induced production of pre- IL-1 alpha precursor or on cell viability or DNA and protein synthesis. Stromal macrophages obtained from the femoral BM of C57Bl/6 mice exposed to BZ (600 or 800 mg/kg body weight) for 2 days were incapable of processing the 34-Kd pre-IL-1 alpha to the mature 17-Kd cytokine when stimulated in culture with LPS. Stromal macrophages from mice coadministered BZ and indomethacin, a prostaglandin H synthase (PHS) inhibitor that has been shown to prevent BZ-induced myelotoxic and genotoxic effects in mice when coadministered with benzene were able to convert the pre-IL-1 alpha to mature cytokine. Administration of recombinant murine IL-1 alpha (rMuIL-1 alpha) to mice before a dose of BZ that causes severe depression of BM cellularity completely prevents BM depression, most probably by bypassing the inability of the stromal macrophage in BZ-treated animals to process pre-IL-1 alpha to the mature cytokine.     

Reproducibility of flow cytometric assessment of follicular tumours of the thyroid.

The reproducibility of the DNA index of paraffin wax sections from 44 follicular tumours of the thyroid (18 follicular adenomas and 26 follicular carcinomas), which had been assessed by flow cytometry was analysed in two laboratories, using consecutive sections of the same specimens and two different commercially available flow cytometers. Two slightly different cell preparation and staining techniques were used in the two laboratories. Using strictly defined criteria the histograms were classified blind as diploid, peritetraploid, aneuploid, or inadequate and insufficient by two independent investigators. Both the concordance between the two different flow cytometers and the agreement of duplicate assessments within the same flow cytometers were assessed. The mean coefficient of variation of the G0/G1 peak of the diploid tumours in the PARTEC flow cytometer was 5.5 (range 2.3-9.8) and in the FACS flow cytometer 5.2 (range 3.7-8.3); this difference was not significant. There was concordance of classification between the two laboratories in 35 of 36 cases. In 25 cases (18 diploid, seven aneuploid) the intralaboratory variation showed a 100% concordance in histogram classification. It is concluded that flow cytometer DNA index assessment of follicular tumours of the thyroid is reproducible and can be used to evaluate the discriminating and prognostic value of this feature.     

<Emphasis Type="Italic">TCF7L2</Emphasis>variant genotypes and type 2 diabetes risk in Brazil: significant association,but not a significant tool for risk stratification in the general population

Background  

Genetic polymorphisms of the TCF7L2 gene are strongly associated with large increments in type 2 diabetes risk in different populations worldwide. In this study, we aimed to confirm the effect of the TCF7L2 polymorphism rs7903146 on diabetes risk in a Brazilian population and to assess the use of this genetic marker in improving diabetes risk prediction in the general population.     

Direct evidence for the involvement of carbohydrate sequences in human sperm-zona pellucida binding

Several lines of evidence indicate that mammalian fertilization is initiated via a binding process that is dependent upon the recognition of oligosaccharide sequences associated with zona pellucida (ZP) glycoproteins. Here, specific chemical and enzymatic methods were employed to modify human ZP and to test their effects on sperm binding in the hemizona assay system (HZA). Periodate oxidation of human ZP under very mild conditions (10 min, 0 degrees C, 1 mM sodium m- periodate) that attacks only terminal sialic acid resulted in a 30% loss of human sperm binding in the HZA [hemizona index (HZI) = 70.2 +/- 10.9, n = 22; P < 0.05]. Periodate oxidation under mild conditions (1 h, 23 degrees C, 10 mM sodium m-periodate) caused a 40% decrease in binding (HZI = 60.8 +/- 10.3; n = 24; P< 0.01). Treatment of human ZP with neuraminidase caused a substantial increase in sperm binding to human ZP (HZI = 297 +/- 45, n = 22; P < 0.01). These findings indicate that there are sialic acid dependent binding sites coexisting with binding sites that are obscured by sialic acid. To determine the periodate sensitivity of these obscured sites, hemizona were first digested with neuraminidase and subsequently subjected to mild periodate oxidation. The combined enzymatic and chemical treatments caused a 79% decrease in sperm binding compared to control hemizona (HZI = 20.7 +/- 4.4, n = 16; P < 0.001). Human sperm-ZP interaction was also increased by digestion of human ZP with endo-beta-galactosidase (HZI = 710 +/- 232, n = 14; P < 0.01), indicating that potential binding sites for spermatozoa are also obscured by lactosaminoglycan sequences. These studies support a definitive role for the involvement of ZP-associated glycans in the binding of human spermatozoa to oocytes.      

Prognostic value of thallium-201 exercise scintigraphy in low-risk patients after Q-wave myocardial infarction: comparison with exercise testing and catheterization.

In a prospective study of 100 consecutive patients discharged after a Q-wave myocardial infarction, the value of reversible ischemia on thallium-201 scintigraphy to assess the risk of cardiac events (death or reinfarction) during 4 years was compared with variables from exercise testing and cardiac catheterization. Patients with markedly impaired left ventricular function [ejection fraction (EF) < or = 0.30] were excluded. During follow-up there were 20 cardiac events (10 cardiac deaths and 10 reinfarctions). Thallium-201 scintigraphy was significantly better than all exercise test variables and better than an EF < 0.40, with good sensitivity and specificity (75 and 51%, respectively). Exercise-induced reversible ischemia on scintigraphy yielded the same information as the presence of multivessel disease. Exercise test variables were of limited value to assess prognosis. Thus, thallium-201 scintigraphy can be used as the only tool to predict future cardiac events in low-risk patients after a Q-wave myocardial infarction.     

Early and 8 year results of aortic valve replacement: a clinical study of 232 patients

The study concerns early and late results of aortic valve replacement (AVR) in 232 patients with aortic valve disease, using the Bj?rk-Shiley tilting-disc prosthesis. Of the 232, 27 patients had some evidence of mitral valve disease with valvulotomy having been undertaken in 7 previously, and in 12 at the time of the aortic valve replacement. Patients who underwent simultaneous mitral valve replacement and/or aorta coronary artery bypass grafting are not included in this analysis. To establish predictions of early death and late survival the patients were divided into two groups (A and B), taking 6 pre-operative risk factors into consideration: systolic pressure gradient greater than or equal to 100 mmHg; NYHA class IV; depressed left ventricular function (heart failure); previous valvulotomy of the aortic valve; advanced age (greater than or equal to 70 years) and surgery during the acute stage of bacterial endocarditis. In group A, consisting of 132 patients with no preoperative risk factors, early mortality was 1.5% (2/132). In group B, with 1 or more risk factors, early mortality amounted to 15% (15/100), (P less than 0.01). Subdividing group B into patients with one of the first three risk factors and patients with two or three of these risk factors, mortality was 12% (9/73) and 27% (6/22), respectively. Actuarially determined survival curves showed an 8-year survival rate of 84.2% for patients in group A and 59.6% for patients belonging to group B. Corrected for early mortality, however, the difference in late mortality is not significant. Analysis showed that early mortality was related to myocardial preservation: results for coronary perfusion and cardioplegic arrest were similar, but results were far less good when hypothermic ischaemic arrest was applied. Late results were less favourable in patients who had prior mitral valve disease not requiring mitral valve replacement at the time of AVR, or in those who developed mitral valve disease. The results allow the authors to conclude that AVR is a relatively safe procedure with a low operative mortality and few postoperative complications in patients with no 'risk factors'.     

Colonic motility diagnosis based on colonic pressure

Manometry of the alimentary tract is a valuable and widely used means to evaluate and diagnose the function of the alimentary tract. However, the measurement can be inconvenient due to the invasive method used, and the many factors affecting results. Research on colonic pressure data is even more insufficient. This paper deals with colonic pressure data via an improved method ensuring that pressure data of the whole colon is available. The data is analysed based on the learning vector quantization (LVQ) method. Testing results show that this method distinguishes the normal data and the abnormal data, consistently with the original diagnoses. This method can serve as an assistant diagnosis of colonic motility and contributes to further research on colonic motility based on pressure data.