Cell cycle control of a Burkitt lymphoma cell line: responsiveness to growth signals engaging the C3D/EBV receptor.

CR2, the receptor for the C3d fragment of the third complement component and for Epstein-Barr virus (EBV) has been shown, on mouse B cells, to be involved in the control of B-cell proliferation by acting as a receptor for macrophage-derived growth factors. We examined whether the growth of a Burkitt lymphoma cell line, RAJI, could be influenced by ligands of human CR2. In serum-free culture, purified human C3d, as well as three monoclonal antibodies to distinct epitopes on human CR2, were capable of enhancing the growth rate of RAJI cells two to five-fold. This effect could not be observed if even trace amounts of serum were present in the culture medium. Simultaneous addition of pairs of antibodies did not enhance the growth rate, suggesting that a particular engagement of CR2 may be critical in order to induce a stimulatory effect. These results indicate that in a homologous serum-free human B-cell system human C3d as well as monoclonal antibodies to human CR2 can induce B-cell proliferation and that CR2-mediated triggering of B cells can be induced via epitopes other than the C3d-binding site. In addition we conclude that--unlike normal human B cells--at least some human B-lymphoma cells respond to CR2-mediated stimuli in the absence of any T-cell derived factors. Therefore the control mechanisms exerted through CR2 must still be intact on these autonomously growing cells.     

影响盐酸维拉帕米脉冲释放片体外“时滞”的因素考察

目的：考察影响盐酸维拉帕米脉冲片控时效果的因素。方法：通过外溶出的方法考察脉冲控释片的时滞,主要包括溶出条件和处方因素两方面。结果：介质的酸碱度不影响制剂的控时效果;转速不影响制起崩时间,但对溶出速度有一定的影响;粘度越大的介质,释药时滞也越大。包衣用量增加、控时层中亲水性成分PEG6000含量减小、控时层中PEG类型的分子量的增加,均能使药物释放滞后时间明显增大;包衣颗粒大小对控时效果基本没有影响。结论：溶出条件作用因素的考察为进一步的体内研究奠定了基础;处方因素的考察为制剂的时滞调控和释药特征研究作了准备。     

Hydrogen peroxide inhibits gap junctional intercellular communication in glutathione sufficient but not glutathione deficient cells

Cell to cell communication via gap junctions is essential in the maintenance of the homeostatic balance of multicellular organisms. Aberrant intercellular gap junctional communication (GJIC) has been implicated in tumor promotion, neuropathy and teratogenesis. Oxidative stress has also been implicated in similar pathologies such as cancer. We report a potential link between oxidative stress and GJIC. Hydrogen peroxide, a known tumor promoter, inhibited GJIC in WB-F344 rat liver epithelial cells with an I50 value of 200 microM. Inhibition of GJIC by H2O2 was reversible as indicated by the complete recovery of GJIC with the removal of H2O2 via a change of fresh media. Free radical scavengers, such as t-butyl alcohol, propylgallate, and Trolox, did not prevent the inhibition of GJIC by H2O2, which indicated that the effects of H2O2 on GJIC was probably not a consequence of aqueous free radical damage. The depletion of intracellular GSH reversed the inhibitory effect of H2O2 on GJIC. The treatment of glutathione- sufficient cells with H2O2 resulted in the hyperphosphorylation of connexin43, which is the basic subunit of the hexameric gap junction protein, as determined by Western blot analysis. TPA, a well-known tumor promoter, also inhibits GJIC via hyperphosphorylation of GJIC, which is a result of protein kinase-C activation. However, H2O2 also induced hyperphosphorylation in GSH-deficient cells that had normal rates of GJIC. Therefore, the mechanism of GJIC inhibition must be different from the TPA-pathway and involves GSH.      

A comparative study of the different diagnostic criteria of gestational diabetes mellitus and its incidence

Background

High prevalence of diabetes and genetic predisposition to metabolic syndrome among Indians places Indian women at risk to develop gestational diabetes mellitus (GDM) and its complications. Literature defines multiple criteria for GDM. This prospective study compares available diagnostic criteria for GDM in Indian women and their correlation with perinatal morbidity.

Method

Nine hundred and forty-eight consecutive voluntary nondiabetic pregnant women were recruited for the study. Seven hundred and twenty-three of these (mean age 23.45 years; 75.7% < 25 years) who reported for the follow-up were screened for GDM at 24–28 weeks gestation by American College of Obstetrics and Gynaecology (ACOG) guidelines and World Health Organization (WHO) criteria. Glycated haemoglobin (HbA_1c) and fasting and two-hours postglucose plasma insulin levels were also analysed. Pregnancy outcome was known for 291 of these. Concordance of risk factors and perinatal complications was analysed with respect to GDM.

Results

Prevalence of GDM at 24–28 weeks gestation was found to be 4.8% by WHO criteria, 6.36% by Carpenter and Coustan's criteria, and 3.5% by O'Sullivan's criteria. Prevalence was marginally higher in women of higher age, having past history of abortion or family history of diabetes mellitus (DM) (P > 0.05). None of these women had HbA_1c > 6%. Relative risk of abnormal delivery (pregnancy outcome) was 1.93, 1.39, and 1.17 in women with GDM by O'Sullivan's, WHO, and Carpenter's criteria, respectively (P > 0.05). Abnormal deliveries were marginally higher in women with high postglucose load insulin levels. Mean weight of the newborns was essentially the same in GDM and nonGDM women by any of the criteria. One-hour and two-hours postglucose values were more sensitive in diagnosing GDM by O'Sullivan's criteria while fasting plasma glucose value had the poorest specificity with 2.5% of nonGDM women having values above the cut-off. Modifications of these criteria did not im-prove their predictive value for abnormal delivery over that of O'Sullivan's criteria.

Conclusion

Prevalence of GDM and abnormal delivery in women < 35 years of age is low. Therefore, global screening for GDM may not be very useful in women < 25 years of age unless family history of DM or past history of abortion is present. Existing evidence is inadequate to justify the switchover from O'Sullivan's criteria for diagnosis of GDM.     

薄荷醇与樟脑对烟酰胺的促皮渗透作用的研究

目的:研究薄荷醇和樟脑对烟酰胺透皮吸收的影响。方法:用两室扩散池体外透皮实验装置,以兔皮为屏障,使用不同浓度的薄荷醇和樟脑,测定烟酰胺的透皮百分率。结果:含1％薄荷醇组和含1％樟脑组的烟酰胺透皮百分率无显著增加,而含1％薄荷醇和1％樟脑组,含3％薄荷醇组,含3％樟脑组,含3％薄荷醇和3％樟脑组的烟酰胺透皮百分率明显增加。结论:薄荷醇和樟脑均对烟酰胺有促皮渗透作用,两药作用强度相似,两药使用时具有协同作用。     

Identification of women with an increased risk of developing radiation-induced breast cancer: a case only study

Introduction

Medroxyprogesterone acetate (MPA) induces estrogen receptor (ER)-positive and progesterone receptor (PR)-positive ductal invasive mammary carcinomas in BALB/c mice. We sought to reproduce this MPA cancer model in C57BL/6 mice because of their widespread use in genetic engineering. Within this experimental setting, we studied the carcinogenic effects of MPA, the morphologic changes in mammary glands that are induced by MPA and progesterone, and the levels of ER and PR expression in MPA-treated and progesterone-treated mammary glands. Finally, we evaluated whether the differences found between BALB/c and C57BL/6 mouse strains were due to intrinsic differences in epithelial cells.

Methods

The carcinogenic effect of MPA was evaluated in C57BL/6 mice using protocols proven to be carcinogenic in BALB/c mice. In addition, BALB/c and C57BL/6 females were treated with progesterone or MPA for 1 or 2 months, and mammary glands were excised for histologic studies and for immunohistochemical and Western blot evaluation of ER and PR. Hormone levels were determined by radioimmunoassay. Isolated mammary epithelial cells were transplanted into cleared fat pads of 21-day-old female Swiss nu/nu mice or control congenic animals.

Results

MPA failed to induce mammary carcinomas or significant morphologic changes in the mammary glands of C57BL/6 mice. The expression of ER-α and PR isoform A in virgin mice was surprisingly much higher in BALB/c than in C57BL/6 mammary glands, and both receptors were downregulated in progestin-treated BALB/c mice (P < 0.05). PR isoform B levels were low in virgin control mice and increased after progestin treatment in both strains. ER-β expression followed a similar trend. No differences in hormone levels were found between strains. Surprisingly, the transplantation of the epithelial mammary gland cells of both strains into the cleared fat pads of Swiss (nu/nu) mice abolished the mammary gland morphologic differences and the ER and PR differences between strains.

Conclusion

C57BL/6 mammary glands are resistant to MPA-induced carcinogenesis and to hormone action. MPA and progesterone have different effects on mammary glands. Low ER-α and PR-A levels in untreated mammary glands may be associated with a low-risk breast cancer profile. Although we cannot at this time rule out the participation of other, untested factors, our findings implicate the stroma as playing a crucial role in the strain-specific differential hormone receptor expression and hormone responsiveness.     

C3bi-binding protein on Candida albicans: temperature-dependent expression and relationship to human complement receptor type 3.

We investigated in detail the previously described capacity of pseudohyphae of Candida albicans to bind C3-coated particles. We show that the expression of the C3bi receptor of C. albicans was dependent upon the growth temperature of the fungi. C. albicans grown at 30 degrees C bound strongly to EAC1423bi, whereas those cells grown at 38.5 degrees C were completely devoid of this capacity. The molecule responsible for the attachment of EAC1423bi was heat labile and trypsin sensitive. Several, but not all, monoclonal antibodies to the alpha-chain of human complement receptor type 3 (CR3) stained C. albicans, and this reactivity was expressed in parallel with the capacity of C. albicans to bind EAC1423bi, i.e., both were dependent on the growth temperature of the fungi and were trypsin sensitive. In contrast to CR3, the binding of EAC1423bi to C. albicans did not require the presence of divalent cations. Rabbit immunoglobulin G antibodies directed against C. albicans inhibited the binding of EAC1423bi to C. albicans but not to human CR3. These inhibiting IgG antibodies recognized antigens expressed on the surface of pseudohyphae but not those of yeast cells. OKM-1, a monoclonal antibody to human CR3 inhibited the attachment of EAC1423bi to CR3 and also to C. albicans. OKM-1 precipitated a 130-kilodalton band from solubilized 125I-labeled C. albicans. We conclude that the complement receptors on C. albicans and human CR3 were antigenically related but not identical and that they differed in their functional characteristics.     

围手术期出血的处理

引言 任何大手术都存在对止血系统的挑战,一些失血总是不可避免的。然而,围手术期大出血仍是外科手术的主要并发症,导致发病率和死亡率升高。对血液供应的安全性和可靠性的担心,需要我们共同努力节约地使用血液制品,以减少异体血液的接触,从而减少输血传播的疾病。因此围手术期出血的处理需要迅速评估,有条理地诊断,以及制定适当的治疗方案。围手术期出血存在两个主要原冈。第一是手术出血,由于在手术部位不能手术控制出血的血管直接造成的。外科手术出血通常以单部位出血为特点,仪局限于手术部位。精细的技术,耐心认真