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. 相似文献
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. 相似文献
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.
相似文献
The author emphasizes that conservative rhinoplasty techniques are frequently satisfactory, but in certain techniques there is a limit to which nasal tips can be reshaped. In certain circumstances, therefore, interruption of the domes of the alar cartilages is suggested to achieve the most satisfactory aesthetic results. 相似文献
In spite of their important impact on populations, a number of diseases - all types of cancer and coronary heart disease in women - are rare events for statistical analysis and often analyzed in designs affected by selection and information biases, such as case-control studies. Large cohort studies based on the storage of biological specimens appear to be the most suitable solution for identifying risks for those diseases.Progetto ATENA, a study on the etiology of major chronic diseases in women is based on this design. Ten thousand women, aged 30–69 years, living in the area of the city of Naples, free of cancer and cardiovascular disease, are being recruited over a four-year period. Ten per cent of the cohort is being randomly selected from the electoral roles, the rest will be volunteers.Information on dietary habits, reproductive history, familiarity for chronic disease, active smoking habits and passive smoking exposure, physical activity, and socio-demographic data are being collected. Clinical data such as blood pressure, anthropometry, and electrocardiogram are also taken. All the participants provide biological samples of blood (fasting drawing) and urine (timed morning spot). The biological samples are processed in order to explore the main areas under study (nutritional markers, metabolism, endocrinology, genetics, environmental exposure markers, thrombogenesis). The samples are stored in liquid nitrogen (–196° C) as soon as the blood and urine processing have been finished. An appropriate follow-up information system on the health status of the participants is being set up to estimate incidence and mortality rates.Corresponding author. 相似文献
Background. The aim of the present study was to assess the cost/efficacy of the pleural tent procedure after upper lobectomy.
Methods. A prospective randomized analysis was performed on 50 patients submitted to upper lobectomy and divided into two groups: group 1 (25 patients) with pleural tent; group 2 (25 patients) without pleural tent.
Results. The univariate comparison between the two groups did not show any significant difference in terms of age, gender, spirometry, smoking history, chronic obstructive pulmonary disease index, side of tumor, arterial oxygen tension, arterial carbon dioxide tension, size and location of tumor, presence of pleural adhesions, length of the stapled parenchyma, and operative time. Pleural tent significantly reduced the days of postoperative air leak (1.2 versus 5.8, p = 0.01), chest tubes (5.4 versus 10.4, p = 0.01), and hospital stay (6.9 versus 10.8, p = 0.01). Moreover, no difference was noted between the two groups in terms of pleural effusion in the first postoperative 48 hours, need of postoperative blood transfusion, and occurrence of other complications.
Conclusions. Pleural tenting after upper lobectomy is a safe and effective procedure and its routine use is warranted. 相似文献
Prospective cohort studies on breast cancer risk among premenopausal women and insulin-like growth factor I (IGF-I) concentrations have so far included only few cases, and have shown inconsistent relative risk estimates. We pooled 220 cases of breast cancer diagnosed before age 50, and 434 control subjects, from three prospective studies in New York (USA), Ume? (Northern Sweden) and Milan (Italy), and we measured IGF-I and insulin-like growth factor binding protein 3 (IGFBP-3) with common enzyme-linked immunosorbent assays. Overall, IGF-I and IGFBP-3 measurements obtained by the common method showed a positive but not significant relationship with breast cancer risk (odds ratios (ORs) 0.90 [95% confidence intervals (95% CI) 0.50-1.62], 1.63 [0.89-2.97], 1.46 [0.78-2.73] and 1.41 [0.75-2.63] for quintiles of IGF-I, and ORs 0.98 [0.54-1.75], 1.06 [0.59-1.91], 1.04 [0.58-1.87] and 1.77 [0.97-3.24] for quintiles of IGFBP-3). Our results give only moderate support for an association of blood IGF-I with breast cancer risk in young women. 相似文献