Risk factors for fatal breast cancer in African-American women and White women in a large US prospective cohort

African-American women have a higher lifetime risk of fatal breast cancer than do White women. Recent studies suggest that breast cancer risk factors may vary by race. The authors examined risk factors for fatal breast cancer in postmenopausal African-American women and White women in a large US prospective cohort. In 1982, 21,143 African-American women and 409,093 White women in the Cancer Prevention Study II completed a questionnaire on reproductive, medical, anthropometric, and demographic factors. During a 20-year follow-up, 257 deaths from breast cancer occurred among African-American women and 4,265 among Whites. Cox proportional hazards modeling was used to calculate multivariate-adjusted rate ratios, stratified by race. Higher body mass index, taller height, and physical inactivity were associated with increased breast cancer mortality rates in both groups. A college education was associated with higher mortality from breast cancer only in Africa-American women (hazard ratio = 1.62, 95% confidence interval: 1.13, 2.30; p(trend) = 0.01, vs. less than a high school education). Most other risk factors were associated with breast cancer rates similarly in both groups. With few exceptions, established breast cancer risk factors were similarly associated with risk of death from breast cancer among African-American women and White women.     

Pretranslational control of tryptophan oxygenase levels in Morris hepatoma and host liver.

Tryptophan oxygenase is present and hormonally inducible in host livers but is absent in transplanted Morris hepatomas examined under basal conditions as well as in hormonally induced animals. Studies were performed to determine whether the absence of tryptophan oxygenase in hepatomas is mediated by an alteration in the translational efficiency or the level of the messenger RNA (mRNA) for tryptophan oxygenase. The tissue level of the specific mRNA coding for tryptophan oxygenase was quantitated in an mRNA-dependent Krebs ascites cell-free protein-synthesizing system. The enzyme levels and mRNA activities in host livers and hepatomas from control rats and rats given injections of an inducing dose of hydrocortisone were compared; they indicate that the induction of tryptophan oxygenase in host livers by hormones is accompanied by a proportional increase in the level of its mRNA, whereas in the transplanted hepatomas the tryptophan oxygenase catalytic activity and the mRNA coding for this enzyme were undetectable in both control and glucocorticoid-induced animals. No functional mRNA for tryptophan oxygenase could be detected in the total polyadenylate-containing mRNA isolated from the Morris hepatoma cells. The hepatomas contained normal levels of cytoplasmic glucocorticoid receptor that could bind glucocorticoid, undergo "activation," and translocate to both normal and neoplastic nuclei. Thus, deletion of tryptophan oxygenase in hepatomas is a consequence of the absence of the gene product, i.e., the tryptophan oxygenase mRNA, which codes for its synthesis; this is not due to detectable alterations in the ability of the glucocorticoid receptor to bind the steroid hormone, or of the hormone-receptor complex to undergo activation, or of the activated steroid-receptor complex to bind to nuclei derived from the hepatoma or normal liver.     

Creutzfeldt--Jakob Disease in Recipients of Human Growth Hormone in the United Kingdom: A Clinical and Radiographic Study

In the past 3 years there have been five further cases, in additionto one case reported in 1985, of Creutzfeldt-Jakob disease inrecipients of human growth hormone in the United Kingdom. Theclinical findings of two of these cases are described, demonstratinga typical presentation with a predominantly cerebellar syndromeat onset which is not commonly a presenting feature of sporadicCreutzfeldt-Jakob disease. In one case a ^99mTc hexamethylpropylenaminesingle photon emission tomographic scan showed marked impairmentof tracer uptake in the basal ganglia and cerebral cortex ata time when the clinical picture was predominantly cerebellar.This technique may be useful in early diagnosis. In the othercase post mortem examination of the brain showed prominent amyloiddeposition in the cerebellum, which has not been described previouslyin pituitary-hormone related Creutzfeldt-Jakob disease. Thepreviously published cases of growth hormone-related Creutzfeldt-Jakobdisease are reviewed and reasons for the particular clinicalpattern seen are discussed.     

Development of specific receptors for N-formylated chemotactic peptides in a human monocyte cell line stimulated with lymphokines

A human monocyte-like cell line, U937, when grown in continuous culture, does not secrete lysosomal enzymes or migrate towards chemotactic factors. When the cells are stimulated by lymphokines, however, they develop the ability both to migrate directionally and to secrete enzymes in response to several types of chemoattractants. The development, by stimulated cells, of chemotactic and secretory responses to one class of chemoattractants, the N- formylated peptides, is accompanied by the appearance on the cells of specific binding sites for these substances. Using tritiated N-formyl- methionyl-leueyl-phenylalanine (fMet-Leu-[(3)H]Phe) as a ligand, it was determined that unstimulated U937 cells possess no detectable binding sites. However, after stimulation with lymphocyte culture supernates for 24, 48, and 72 h, they developed 4,505 (+/-) 1,138, 22,150(+/-) 4,030, and 37,200 (+/-) 8,000 sites/cell, respectively. The dissociation constants for the interaction of fMet-Leu-[SH]Phe with the binding sites were approximately the same regardless of stimulation time and ranged between 15 and 30 nM. The binding of fMet-Leu-[(3)H]Phe by stimulated U937 cells was rapid and readily reversed by the addition of a large excess of unlabeled peptide. The affinity of a series of N-formylated peptides for binding to U937 cells exactly reflected the potency of the peptides in inducing lysosomal enzyme secretion and chemotaxis. The availability of a continuous human monocytic cell line that can be induced to express receptors for N-formylated peptides will provide a useful tool not only for the characterization of such receptors but also for the delineation of regulatory mechanisms involved in cellular differentiation and the chemotactic response.     

不同相对分子质量玻璃酸钠对膝关节镜术后关节功能恢复的作用比较

目的:观察关节腔内留置不同相对分子质量玻璃酸钠对膝关节镜术后早期疼痛及功能恢复的影响。方法:于2005-11/2006-05选择北京大学人民医院骨关节科收治的行膝关节镜手术患者60例。关节镜手术中根据不同诊断分别行半月板成形术、游离体取出术以及软骨成形术。60例患者按随机数字表法分为3个实验组,分别为Mr1.5×106～2.5×106玻璃酸钠组,Mr3×106玻璃酸钠组,Mr6×106玻璃酸钠组。术后关节腔内注入不同相对分子质量玻璃酸钠2.0～2.5mL,并被动屈伸膝关节20次,使玻璃酸钠均匀分布于关节内。术后第1天开始股四头肌力量锻炼,坐在床边屈膝活动,并可下床。术后1周拆除缝线,术后6周门诊复查。分别于术前、术后1,2,3d,1,6周采用同一评分量表进行自觉疼痛程度、日常生活活动能力、膝关节屈曲角度测评,评分越高,功能恢复越好。结果:纳入患者60例,均进入结果分析。①自觉疼痛程度测定:术后6周Mr1.5×106～2.5×106,3×106,6×106玻璃酸钠组自觉疼痛程度评分均高于术前[分别为(8.5±1.3),(7.3±2.2)分;(8.5±1.3),(7.3±2.2)分;(8.5±1.3),(7.3±2.2)分]。②日常生活活动能力测定:术后6周Mr1.5×106～2.5×106,3×106,6×106玻璃酸钠组日常生活活动能力评分均高于术前[分别为(60.5±8.4),(59.3±7.0)分;(63.4±8.2),(59.4±8.3)分;(66.9±3.8),(53.8±19.0)分]。③膝关节屈曲角度评分:术后6周Mr1.5×106～2.5×106,3×106,6×106玻璃酸钠组膝关节屈曲角度评分均高于术前[分别为(9.1±1.4),(5.8±2.7)分;(8.1±3.1),(7.2±3.5)分;(6.3±3.8),(5.5±3.1)分]。④综合评分:术后6周Mr1.5×106～2.5×106,3×106,6×106玻璃酸钠组综合评分均高于术前[分别为(88.1±7.7),(79.8±11.1)分;(91.4±6.8),(84.9±13.7)分;(91.2±10.7),(73.5±23.7)分]。关节腔内留置3种不同相对分子质量玻璃酸钠在膝关节镜术后近期各项评分差异均无显著性意义(P>0.05)。结论:关节腔内留置不同相对分子质量玻璃酸钠在膝关节镜术后近期康复中具有相似的效果。     

Care of post-traumatic spinal cord injury patients in India: An analysis

Background:

The spinal cord injured patients if congregated early in spinal units where better facilities and dedicated expert care exist the outcome of treatment and rehabilitation, can be improved. The objective of this study is to find out the various factors responsible for a delay in the presentation of spinal injury patients to the specialized spinal trauma units and to suggest steps to improve the quality of care of the spinal trauma patients in the Indian setup.

Materials and Methods:

Sixty patients of traumatic spinal cord injury admitted for rehabilitation between August 2005 and May 2006 were enrolled into the study and their data was analyzed.

Results:

Eighty-five per cent of the spinal cord injured patients were males and the mean age was 34 years (range 13-56 years). Twenty-nine (48.33%) of the spinal injuries occurred due to fall from height. There was an average of 45 days (range 0-188 days) of delay in presentation to a specialized spinal unit and most of the time the cause for the delay was unawareness on the part of patients and/or doctors regarding specialized spinal units. In 38 (62.5%) cases the mode of transportation of the spinal cord injured patient to the first visited hospital was by their own conveyance and the attendants of the patients did not have any idea about precautions essential to prevent neurological deterioration. Seventeen (28.33%) patients were given injection solumedrol with conservative treatment, 35 (60%) patients were given only conservative treatment and seven patients were operated (11.66%) upon at initially visited hospital. Of the seven patients operated five were fixed with posterior Harrington instrumentation (71.42%) and two (28.57%) were operated by short segment posterior pedicle screw fixation. None of the patients were subjected to physiotherapy-assisted transfers or wheel chair skills or even basic postural training, proper bladder/ bowel training program and sitting balance.

Conclusion:

Awareness on the part of the general population, attendants of the patients, clinical and paraclinical team regarding spinal cord injury needs to be addressed. Safe mode of transportation of spinal cord injured patient and early presentation at tertiary spinal care center with comprehensive spinal trauma care team should be stressed upon.     

Talin1 is required for integrin-dependent B lymphocyte homing to lymph nodes and the bone marrow but not for follicular B-cell maturation in the spleen

Talin1 is a key integrin coactivator. We investigated the roles of this cytoskeletal adaptor and its target integrins in B-cell lymphogenesis, differentiation, migration, and function. Using CD19 Cre-mediated depletion of talin1 selectively in B cells, we found that talin1 was not required for B-cell generation in the bone marrow or for the entry of immature B cells to the white pulp of the spleen. Loss of talin1 also did not affect B-cell maturation into follicular B cells but compromised differentiation of marginal zone B cells. Nevertheless, serum IgM and IgG levels remained normal. Ex vivo analysis of talin1-deficient spleen B cells indicated a necessary role for talin1 in LFA-1 and VLA-4 activation stimulated by canonical agonists, but not in B-cell chemotaxis. Consequently, talin1 null B splenocytes could not enter lymph nodes nor return to the bone marrow. Talin1 deficiency in B cells was also impaired in the humoral response to a T cell-dependent antigen. Collectively, these results indicate that talin1 is not required for follicular B-cell maturation in the spleen or homeostatic humoral immunity but is critical for integrin-dependent B lymphocyte emigration to lymph nodes and optimal immunity against T-dependent antigens.