结肠癌和直肠癌危险因素的巢式病例对照研究

目的：探讨结肠癌和直肠癌的危险因素。方法：应用巢式病例对照研究方法,对一个6万余人队列随访10年队列中196例新发结、直肠癌病例作为病例组;从该队列中随机抽取980名正常人作为对照组,对有关暴露因素进行单因素分析和多因素非条件logistic回归分析,结果：年龄在病例组和对照之间差异有显著性,病例组年龄高于对照组,且结肠癌的发病年龄高于直肠癌。多因素分析表明,除年龄外,粘液血便中、肠息肉史与结肠癌关系密切,OR值分别为：2．961（95％CI：1．202－7．298）和8．941（95％CI：1．820－43．926）,饮用混合水与直肠癌的OR值为1．823（95％CI:1．024－3．247）。结论：结、直肠癌的危险因素不尽相同。除年龄是结、直肠癌发病的一个共同重要因素外,肠息肉史和粘液血便史与结肠癌有关联,而饮用混合水则与直肠癌关系密切。     

Surface antigenic determinants on human pluripotent and unipotent hematopoietic progenitor cells

RFB-1 is a monoclonal antibody previously shown to react with granulocyte-monocyte progenitors (CFU-GM) and immature lymphoid cells in human bone marrow. RFB-HLA-DR is a monoclonal antibody that reacts with HLA-DR (la-like) antigens. The present study shows that the bone marrow subset reactive with both RFB-1 and RFB-HLA-DR contains all the cells that give rise to mixed hematopoietic colonies (derived from CFU- GEMM; a pluripotent human progenitor cell) as well as to megakaryocytic (megakaryocyte-CFU-derived) and erythropoietic (derived from erythroid burst-forming units, BFU-E) colonies, as shown by fluorescence- activated cell sorting and complement-mediated cytotoxicity. These results indicate that CFU-GEMM, BFU-E, and megakaryocyte-CFU express RFB-1 and la-like antigens. RFB-1 antigen is also expressed on erythroid colony-forming units (CFU-E). RFB-1 and RFB-HLA-DR are useful reagents in the study of hematopoietic stem cells.     

Mechanism of red cell 2,3-diphosphoglycerate increase in neonatal lambs

The tenfold increase in red cell 2,3-diphosphoglycerate (DPG) concentration that occurs during the first 5 days of life in lambs is an important adaptation to extrauterine life. In lambs, DPG reduces hemoglobin oxygen affinity by the Bohr effect. Our data on 10 neonatal lambs suggest that the biochemical mechanism underlying this DPG increase involves the following: (1) a rise in plasma glucose from 40 to 100 mg/dl in the first 48 hr of life, which allows for increased glucose consumption in the highly glucose-permeable neonatal RBC; (2) a transitory rise in blood pH begins at birth, peaks at about 20 hr, and falls slightly; (3) the pH increase coincides with a threefold increase in RBC fructose-1,6-diphosphate (FDP) concentration due, we believe, to pH activation of phosphofructokinase; (4) glycolytic intermediates after the glyceraldehyde-3-phosphate dehydrogenase (GAPD) step do not rise in the first 24 hr of life, possibly due to insufficient inorganic phosphate (Pi), a substrate of GAPD; (5) plasma Pi increases from about 7 mg/dl at birth to 11 mg/dl at 72 hr, activates the GAPD, and FDP levels decline; and (6) the in vitro activity of the DPG synthetic enzyme, DPG mutase, is increased 12-fold in neonatal compared to adult RBC. We conclude that the postnatal rise in DPG is explained at least in part by the sequential effects of these metabolic changes.     

Valuing the benefit of diagnostic testing for genetic causes of idiopathic developmental disability: willingness to pay from families of affected children

Idiopathic developmental disability (DD) has been found to put significant psychological distress on families of children with DD. The cause of the disability, however, is unknown for up to one-half of the affected children. Chromosomal abnormalities identified by cytogenetic analysis are the most frequently recognized cause of DD, although they account for less than 10% of cases. Array genomic hybridization (AGH) is a new diagnostic tool that provides a much higher detection rate for chromosomal imbalance than conventional cytogenetic analysis. This increase in diagnostic capability comes at greater monetary costs, which provides an impetus for understanding how individuals value genetic testing for DD. This study estimated the willingness to pay (WTP) for diagnostic testing to find a genetic cause of DD from families of children with DD. A discrete choice experiment was used to obtain WTP values. When it was assumed that AGH resulted in twice as many diagnoses and a 1-week reduction in waiting time compared with conventional cytogenetic analysis, this study found that families were willing to pay up to CDN$1118 (95% confidence interval, $498–1788) for the expected benefit. These results support the conclusion that the introduction of AGH into the Canadian health care system may increase the perceived welfare of society, but future studies should examine the cost-benefit of AGH vs cytogenetic testing.     

Dominant versus recessive traits conveyed by allelic mutations – to what extent is nonsense-mediated decay involved?

Mutations in ROR2 , encoding a receptor tyrosine kinase, can cause autosomal recessive Robinow syndrome (RRS), a severe skeletal dysplasia with limb shortening, brachydactyly, and a dysmorphic facial appearance. Other mutations in ROR2 result in the autosomal dominant disease, brachydactyly type B (BDB1). No functional mechanisms have been delineated to effectively explain the association between mutations and different modes of inheritance causing different phenotypes. BDB1-causing mutations in ROR2 result from heterozygous premature termination codons (PTCs) in downstream exons and the conveyed phenotype segregates as an autosomal dominant trait, whereas heterozygous missense mutations and PTCs in upstream exons result in carrier status for RRS. Given that the distribution of PTC mutations revealed a correlation between the phenotype and the mode of inheritance conveyed, we investigated the potential role for the nonsense-mediated decay (NMD) pathway in the abrogation of possible aberrant effects of selected mutant alleles. Our experiments show that triggering or escaping NMD may cause different phenotypes with a distinct mode of inheritance. We generalize these findings to other disease-associated genes by examining PTC mutation distribution correlation with conveyed phenotype and inheritance patterns. Indeed, NMD may explain distinct phenotypes and different inheritance patterns conveyed by allelic truncating mutations enabling better genotype–phenotype correlations in several other disorders.     

误诊为药源性肌病的抗合成酶综合征1例

1例42岁男性慢性乙型肝炎患者口服拉米夫定（100mg,1次／d）和阿德福韦酯（10mg,1次／d）治疗,约1个月后出现四肢肌肉酸痛、乏力,双下肢水肿。实验室检查：肌酸激酶9368U／L,肌红蛋白〉4317o,μg／L。肌电图示右侧三角肌肌源性损害。疑为横纹肌溶解症。停用拉米夫定及阿德福韦酯,肌酸激酶下降,肌无力症状好转。1年后,患者再次出现双下肢水肿并腹胀伴间断发热。肌酸激酶5546U／L,肌红蛋白〉1200μg／L,抗Jo-1抗体阳性。诊断：多发性肌炎,抗合成酶综合征。给予保肝、利尿、营养神经等治疗。2周后,加用恩替卡韦0．5mg、1次／d抗病毒治疗。2个月后,给予糖皮质激素治疗。1个月后,患者四肢肌肉酸痛、无力症状基本缓解,复查肌酸激酶正常。     

Ciliary dysfunction and obesity

Mok CA, Héon E, Zhen M. Ciliary dysfunction and obesity.
Obesity associates with increased health risks such as heart disease, stroke and diabetes. The steady rise in the obese population worldwide poses an increasing burden on health systems. Genetic factors contribute to the development of obesity, and the elucidation of their physiological functions helps to understand the cause, and improve the prevention, diagnosis and treatment for this disorder. Primary cilia are evolutionarily conserved organelles whose dysfunctions lead to human disorders now defined as ciliopathies. Human ciliopathies present pleiotropic and overlapping phenotypes that often include retinal degeneration, cystic renal anomalies and obesity. Increasing evidence implicates an intriguing involvement of cilia in lipid/energy homeostasis. Here we discuss recent studies in support of the key roles of ciliary genes in the development and pathology of obesity in various animal models. Genes affecting ciliary development and function may pose promising candidate underlying genetic factors that contribute to the development of common obesity.     

阴茎折断4例报告并文献复习

目的：报告4例阴茎折断,并对其诊断、治疗和预后进行文献复习,以提高对阴茎折断的认识水平。方法：回顾性分析4例阴茎折断患者的临床资料,结合国内、外文献对其病理、临床表现、诊断、治疗和预后进行探讨。其中3例通过临床表现确诊,1例通过超声波检查确诊。4例均急诊行阴茎血肿清除加白膜修补术。结果：术后随访2—120月,平均81个月,阴茎外观正常,性生活满意,无阴茎弯曲、痛性勃起、尿道狭窄等并发症。结论：阴茎折断临床罕见,粗暴性交为其主要病因,多伴有典型病史,急诊手术效果佳,并发症低,为阴茎折断的最佳治疗方法。     

PARP inhibition in atherosclerosis and its effects on dendritic cells,T cells and auto-antibody levels

Objective

Atherosclerosis is a chronic inflammatory process. Poly(ADP-ribose) polymerase-1 (PARP), a nuclear enzyme linked to DNA repair, has been shown to be involved in atherogenesis; however, the effects on dendritic cells, T cells and serum auto-antibody levels are not fully understood.

Methods

Male Apoe^-/- mice on a western diet were treated with the PARP inhibitor 1NO-1001 (n = 15), while the control group (n = 15) received 5% glucose solution for 10 weeks.

Results

Inhibition of PARP markedly reduced atherosclerotic lesion development (p = 0.001). Immunohistochemistry and mRNA analysis revealed a reduced inflammatory compound inside the lesion. Focusing on dendritic cells, INO-1001 reduced number of cells (p = 0.04), grade of activation, represented by I/12 (p = 0.04) and Cd83 (p = 0.03), and grade of attraction, represented by Mip3α (p = 0.02) in the plaque. Furthermore, INO-1001 decreased number of T lymphocyte (p = 0.003) in the lesion and grade of activation after stimulation with oxLDL in vitro. Moreover, serum IgM antibody levels to oxLDL were significantly lower in INO-1001 treated mice (p = 0.03).

Conclusions

Functional blockade of PARP by INO-1001 reduces atherosclerotic lesion development. The anti-atherogenic effect is beside already known mechanisms also moderated due to modulation of DC and T cell invasion and activation, DC attraction as well as IgM antibody levels to oxLDL.