Genetic polymorphism of sulfotransferase 1A1, cigarette smoking,hazardous chemical exposure and urothelial cancer risk in a Taiwanese population

Objectives: To investigate the association between genetic polymorphism of sulfotransferase1A1 (SULT1A1), cigarette smoking, hazardous chemical exposure and urothelial cancer risk in a Taiwanese population. Methods: In a hospital‐based case–control study, a total of 300 urothelial cancer (UC) cases and 300 cancer‐free controls frequency‐matched by age and gender were recruited from September 1998 to December 2005. The SULT1A1 arginine213histidine (Arg213His) polymorphism was genotyped using a polymerase chain reaction–restriction fragment length polymorphism method. Results: We found that the significantly increased UC risks of ever smokers and heavy smokers (≥28 pack‐years) were 2.1 (95% confidence interval [CI] = 1.4–3.3) and 2.2 (95% CI = 1.3–3.6), respectively. An increased UC risk of 1.8 (95% CI = 0.8–3.8) was observed among individuals with more than one item of hazardous chemical exposure, but it was not statistically significant. Compared with study subjects carrying the SULT1A1 Arg/Arg genotype, those with SULT1A1 Arg/His or His/His genotypes have a significantly decreased UC risk (Odds ratio [OR] = 0.5, 95% CI = 0.3–0.8). Heavy smokers carrying the SULT1A1 Arg/Arg genotype have a significantly increased UC risk (OR = 5.2, 95% CI = 2.3–11.6). Individuals who had been exposed to more than one item of hazardous chemicals and who carried the SULT1A1 Arg/Arg genotype have a significantly increased UC risk (OR = 3.7, 95% CI = 1.4–9.7). The highest significant increased UC risk (OR = 16.1, 95% CI = 2.9–87.2) was observed among ever smokers with hazardous chemical exposure and the SULT1A1 Arg/Arg genotype. Conclusions: SULT1A1 Arg213His polymorphism is associated with the development of UC, especially among cigarette smokers exposed to hazardous chemicals.     

Basic fibroblast growth factor prolongs the proliferation of rat cortical progenitor cells in vitro without altering their cell cycle parameters

Basic fibroblast growth factor (bFGF) has been shown to influence the survival, proliferation and differentiation of a variety of cell types in the nervous system. In this investigation we have examined the action of bFGF on: (i) the rate of proliferation; (ii) cell cycle parameters; (iii) the maintenance of cell division; (iv) the recruitment of quiescent cells; and (v) the degree of differentiation of cortical progenitor cells in cultures prepared from E16 rat embryos. The proliferation rate (labelling index) of cortical progenitor cells doubled in the presence of bFGF over 48 h. However, the lengths of the cell cycle phases were unchanged. Clones marked with a recombinant retrovirus on the first day in vitro (DIV) grew significantly larger in the presence of bFGF. Furthermore, many of the clones examined in control cultures had ceased to divide after a maximum of four cell cycles, whereas almost all clonally related cells were still dividing in the presence of bFGF 4 days later, i.e. for at least six cell cycles. Basic FGF also stimulated the division of quiescent progenitor cells, which otherwise would have differentiated or undergone cell death. The degree of neuronal and glial differentiation was studied after 5 DIV using MAP-2 and GFAP immunocytochemistry. In the presence of bFGF, the percentage of MAP-2-labelled cells was less than half that of control cultures, whereas the number of cells immunoreactive for nestin (a marker of progenitor cells) remained very high. Cells immunoreactive for GFAP were present in bFGF-treated cultures, yet were extremely rare in control conditions. These experiments show that bFGF, a potent mitogen for cortical progenitor cells, has no effects on the parameters of their cell cycle but extends their proliferative capability, promotes their survival and delays their differentiation into neurons.      

SURGICAL CORRECTION OF GYNAECOMASTIA IN BODYBUILDERS

SUMMARY Gynaecomastia is a common and well-recognised side-effect of anabolic steroid abuse in athletes. A staging system is proposed and a technique of excision under local anaesthetic described. Careful selection of cases and the use of meticulous technique can achieve good cosmetic results, without risk of recurrence of gynaecomastia.     

Identical nucleotide sequences of the 3'A gamma globin gene enhancer elements from four different chromosomes

We have determined the nucleotide sequence of the 2,360-bp long EcoRI fragment from four chromosomes; this fragment is located 3' to the A gamma globin gene and is considered to contain the enhancer element identified by Bodine and Ley. The chromosomes were from an Arabian sickle cell anemia patient with high Hb F and a homozygosity for haplotype No 31 and from a black sickle cell anemia patient with low Hb F and a homozygosity for haplotype No 19. A third chromosome carried the determinant for a nondeletional hereditary persistence of fetal hemoglobin seen in a Chinese subject, and the fourth was a normal chromosome from a Yugoslavian subject. Twenty-one differences were observed when a comparison was made with the published sequence; no differences were seen between the sequences of the four different samples except for an additional mutation in the Chinese. These data make it unlikely that specific mutations within this sequence are associated with increases in G gamma and A gamma production.     

The effect of hospital size and teaching status on patient experiences with hospital care: a multilevel analysis

BACKGROUND: Hospitals rapidly change structure and organization. Little research has been conducted that documents whether hospital size and teaching status is associated with patient experiences. OBJECTIVES: We sought to assess the effect of hospital size and teaching status on patient experiences with hospital care. METHODS: We undertook a cross-sectional survey of patients discharged from somatic hospitals in Norway. Multilevel regression analysis was used to assess the effect of interest. A total of 21,445 patients from 50 hospitals, categorized as small (36-85 beds, n=17), medium-sized (88-218 beds, n=17), large, nonteaching hospitals (226-725 beds, n=10), and large, teaching hospitals (380-997 beds, n=6) were studied. We used the Patients' Experiences Questionnaire (PEQ), which contains 10 scales measuring different aspects of hospital care. RESULTS: In general, the 10,626 respondents (50% response) rated their experiences as positive. Intraclass correlation ranged from 0.23% (Scale Information About Examinations) to 6.5% (Scale Hospital and Equipment), indicating that a small to modest proportion of the variance was at the hospital level. On 5 of the 10 PEQ scales, a statistically significant part of the variance between hospitals was attributed to hospital category. Small hospitals received the highest ratings and large, teaching hospitals the lowest. Patient characteristics and hospital category contributed together to a proportional reduction in variance ranging from 7.6% (Hospital and Equipment scale) to 53.1% (Hospital Organization scale). CONCLUSION: The effect of hospital category on patient experiences with hospital care was small. Hospital category was not a major determinant of patient experiences during hospitalization.     

A deletion in the proximal untranslated pX region of human T-cell leukemia virus type II decreases viral replication but not infectivity in vivo

The function of untranslated (UT) nucleotide sequences in the proximal portion of the pX region of the human T-cell leukemia virus (HTLV) family of retroviruses remains enigmatic. Previous studies have shown that these sequences are not necessary for the expression of viral proteins or for the induction, transmission, or maintenance of the transformed cell type in vitro. To determine the effect of the UT region in vivo, separate groups of rabbits were inoculated with lethally irradiated, stable clones of the human B-lymphoblastoid cell line, 729, transfected with either a full-length wild-type HTLV-II clone (pH6neo) or a mutant clone containing a 324-bp deletion in the proximal UT portion of pX (pH6neo delta UT[6661-6984]), or nontransfected 729 cells. All rabbits inoculated with either wild-type or pX-deleted HTLV-II developed a similar profile and titer of serum antibodies against HTLV-II antigens, as determined by Western immunoblots, by 4 weeks postinoculation (PI). Antibody titers, as determined by enzyme immunoassay, were similar between the two groups of rabbits and increased over the 18-week period of study. All rabbits were killed at 18 weeks PI, and spleen, peripheral blood lymphocytes (PBMC), bone marrow, and mesenteric lymph node were assayed for HTLV-II tax/rex sequences by quantitative polymerase chain reaction. Virus was detected in all tissues tested from all rabbits inoculated with 729pH6neo cells containing wild-type HTLV-II, which contained between 1.4 and 0.3 mean copies of provirus per cell. In contrast, the distribution and number of provirus copies were more limited in rabbits inoculated with 729pH6neo delta UT(6661-6984) cells containing UT- deleted HTLV-II; in most tissues, there was a fivefold to sevenfold reduction in mean provirus copies per cell as compared with rabbits inoculated with wild-type HTLV-II. All rabbits inoculated with control 729 cells remained negative for HTLV-II infection, as determined by the same techniques. It was concluded that UT sequences in the proximal portion of HTLV-II are not necessary for infection but confer increased replicative capacity in vivo.     

Modeling human lymphoid precursor cell gene therapy in the SCID-hu mouse

Gene therapy of human T-lymphocyte disorders, including acquired immunodeficiency syndrome (AIDS), would be greatly facilitated by the development of an in vivo system in which transduced human hematopoietic stem cells can be used to reconstitute the T-lymphoid compartment. Here we use the SCID-hu mouse as a recipient for human CD34+ hematopoietic progenitor cells transduced in vitro with a retroviral vector carrying the neomycin resistance gene (neoR). The transduced cells engraft and reconstitute the lymphoid compartments of the human thymus implant with as few as 5 x 10(4) CD34+ cells. The neoR gene was expressed at low levels in human thymocytes and there was no apparent effect on thymocyte differentiation as a result of vector transduction. Thus, this SCID-hu mouse system is the first in vivo model showing human thymopoiesis after transduction of exogenous vectors, and should allow preclinical testing of gene therapeutic reagents designed to function in human cells of the T-lymphoid lineage. Because human immunodeficiency virus type 1 infection induces depletion of human thymocytes in SCID-hu mice, this system may be particularly valuable in evaluating efficacy of gene therapies to combat AIDS.