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.     

Intraoperative management of penile erection with intracorporeal phenylephrine during endoscopic surgery

Intraoperative penile tumescence during endoscopic surgery is a troublesome complication that often is refractory to recommended methods of management. We report a new approach of pharmacological management with intracorporeal penile injections of phenylephrine (total dose of 0.1 mg.), which was successful in 3 successive patients. This approach is prompt, safe and reproducible, and it provides sustained resolution of erection without systemic side effects. It is concluded that local intracorporeal penile administration of this sympathomimetic agent appears to be a potent new tool in the armamentarium of the endoscopic surgeon dealing with this frustrating clinical situation, which merits further clinical trial.     

Sinonasal surfactant protein A1, A2, and D gene expression in cystic fibrosis: a preliminary report.

OBJECTIVE: To measure alterations in SPA1, A2, and D gene expression in various forms of inflammatory chronic rhinosinusitis (CRS). STUDY DESIGN AND SETTING: Sinus mucosal biopsies were performed in patients with allergic fungal rhinosinusitis (AFS), CRS with nasal polyposis, cystic fibrosis (CF), and controls. SP mRNA was measured with quantitative polymerase chain reaction. RESULTS: Patients with CF (n = 4) showed significantly increased SPA1 (82-fold), SPA2 (100-fold), and SPD (47-fold) mRNA (P < 0.05) when compared with controls (n = 5). Patients with CRS with nasal polyposis (n = 5) also demonstrated elevated SPA1 (27-fold), SPA2 (13-fold), and SPD (13-fold). Patients with AFS (n = 7) had increased SPA1 (5-fold), SPA2 (9-fold), and SPD (17-fold), but were not statistically significant. CONCLUSION: SPA1, A2, and D are upregulated in various forms of CRS, but are significantly elevated in cystic fibrosis CRS. SIGNIFICANCE: Understanding the role of SPs in CRS will help develop novel treatment approaches for sinonasal pathoses.     

<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.      

Induction of squamous metaplasia in organ cultures of hamster trachea by naturally occurring and synthetic fibers

Asbestos exhibits many properties of classical tumor promoters. These characteristics include the ability to stimulate proliferation and inhibit normal differentiation of cells. In organ cultures of trachea, crocidolite and amosite asbestos stimulate squamous metaplasia, a pathological process in which a rapidly proliferating squamous epithelium replaces the normal epithelium. We hypothesized that the induction of metaplasia depends upon the fibrous nature of asbestos. Accordingly, several naturally occurring and synthetic fibrous materials and their nonfibrous analogues were assessed for their ability to induce metaplastic changes in tracheal mucosa of the Syrian hamster. Exposure to both crocidolite asbestos and fiberglass resulted in significant increases (p less than 0.05) in squamous metaplasia over a range of dosages (1.0, 4.0, 16.0 mg/ml). Attapulgite (palygorskite) and both "long-" and "short-" fiber preparations of chrysotile asbestos had similar but less marked effects. Nonfibrous analogues of each material (riebeckite, antigorite, and glass particles) failed to produce metaplasia. Asbestos, and fibrous materials in general, appear to stimulate squamous metaplasia because of their fibrous geometry.     

Factors associated with the vaccination of international travelers: a multivariate analysis

Travel medicine practice in the United States has not been extensively studied. This study included 1078 consecutive patients who presented to a university-based travel medicine clinic from 1990 through 1994. Analyses of patient demographics, clinic attendance, itineraries, and vaccinations were conducted. Mean patient age (+/- SD) was 37.4 +/- 16.2 years; 626 (58.1%) of the patients were male. Travel duration was 103.1 +/- 242.3 days (median, 21 days), and lead time (defined as the time between clinic presentation and departure for the purpose of this study) was 23.8 +/- 26.5 days (median, 16 days). Destination was the strongest independent factor affecting vaccination practices. A lead time of 31 or more days was associated with significantly elevated odds ratios for all immunobiologicals except immune globulin. These findings underscore the need to educate the traveling public, healthcare providers, and the travel industry about the benefits of seeking medical consultation at least 1 month prior to international travel.     

Debt and other influences on career choices among surgical and primary care residents in a community-based hospital system

BACKGROUND: To evaluate debt and other factors that help formulate the career paths of future surgical and primary care physicians, a survey was undertaken. METHODS: Surgical specialty (SS) and primary care (PC) residents were surveyed regarding demographics, factors influencing choice of specialty, methods of financing education, debt characteristics, and outlooks regarding future earnings and practice characteristics. RESULTS: The clinical years of medical school and personalities of specialists and residents were important factors in career choices for both PC and SS. The length of residency, desirable lifestyle, and working hours were all more important to PC residents. Surgeons found intellectual challenge and procedure-based practice of greater importance. Although not highly regarded by either group, scholarship obligation and student loans had a significantly greater impact on specialty choice and practice plans for PC residents. At the completion of training, 55% of SS and 28% of PC residents anticipate owing more than $100,000. Debt was especially significant in specialty choice and practice plans for PC residents with debt over $100,000. CONCLUSION: Surgical residents are less concerned about personal sacrifices in their quest to become surgeons. It appears state funded scholarships are successful in attracting students to primary care. Both SS and PC residents have significant debt, although, SS residents have greater financial debt than primary care residents. However, the anticipation of indebtedness was a more significant factor in determination of career path for PC.