Insulin-dependent diabetes mellitus (IDDM) is associated with CTLA4 polymorphisms in multiple ethnic groups

Linkage disequilibrium (association) analysis was used to evaluate a candidate region near the CTLA4/CD28 genes using a multi-ethnic collection of families with one or more children affected by IDDM. In the data set unique to this study (Spanish, French, Mexican-American, Chinese and Korean), the transmission/disequilibrium test (TDT) revealed a highly significant deviation for transmission of alleles at the (AT)n microsatellite marker in the 3' untranslated region (P = 0.002) and the A/G polymorphism in the first exon (P = 0.00002) of the CTLA4 gene. The overall evidence for transmission deviation of the CTLA4 A/G alleles is also highly significant (P = 0.00005) in the combined data set (669 multiplex and 357 simplex families) from this study and a previous report on families from USA, Italy, UK, Spain and Sardinia. Significant heterogeneity was observed in these data sets. The British, Sardinian and Chinese data sets did not show any deviation for the A/G polymorphism, while the Caucasian-American data set showed a weak transmission deviation. Strong deviation for transmission was seen in the three Mediterranean-European populations (Italian, Spanish and French) (P = 10(-5)), the Mexican-American population (P = 0.002) and the Korean population (P = 0.03). These results suggest that a true IDDM susceptibility locus (designated IDDM12) is located near CTLA4.      

p53 cDNA突变和突变型p53蛋白表达与大肠癌预后的关系

目的 探讨p53基因cDNA突变和突变型p53基因蛋白表达与大肠腺癌预后的关系。方法 RT-PCR-SSCP检测大肠腺癌组织p53基因cDNA突变,PAb240单抗免疫组化检测大肠腺癌组织突变型p53基因蛋白表达,比较两者与大肠腺癌预后的关系。结果 100例大肠腺癌中,p53基因cDNA突变51例（51%）,突变型p53基因蛋白高表达76例（76%）,两者同步阳性49例;p53基因cDNA突变与突变型p53基因蛋白高表达相关,有显著统计学差异（P<0.01）;与Dukes分期无关（P>0.05）。从Kaplan-Meier 生存曲线和log-rank 分析结果看,突变型p53基因蛋白高表达与大肠腺癌预后无显著统计学差异（P=0.72）;p53基因cDNA突变与大肠腺癌预后有关,统计学差异明显 （P=0.03）。结论 p53基因cDNA突变与突变型p53基因蛋白高表达密切相关。高频率p53基因cDNA突变直接反映大肠腺癌预后差。突变型p53基因高表达则可能受多因素影响,不能直接反映大肠腺癌预后。     

Incidence of infusion reactions to anti-neoplastic agents in early phase clinical trials: The MD Anderson Cancer Center experience

Infusion reactions (IRs) to anti-neoplastic agents require prompt recognition and immediate treatment to avert significant complications. We conducted a retrospective review of the medical records of consecutive patients who received anti-neoplastic therapy in the outpatient treatment center of the Department of Investigational Cancer Therapeutics from January 1, 2013 to November 30, 2013. Of the 597 patients who received treatment, 9 (1.5 %) had IRs (all ≤ grade 2). The most common IRs observed on first occurrence were chills (n = 5), itching, rash, and facial flushing (n = 3 each). There were no IR-related deaths. All the IRs were reversible with appropriate symptomatic treatment and the therapy was completed after temporary cessation of infusion in 7 of the 9 patients. The infusion was stopped in 2 patients due to symptoms suggestive of IgE-mediated allergic reaction and cytokine storm. Five of the 8 patients who were re-challenged with the same therapy developed a similar reaction. However, the infusion was completed in 4 of the 5 patients after administration of intravenous diphenhydramine and/or hydrocortisone, or slowing the rate of infusion. And, subsequent cycles with the same agents were uneventful. IRs to anti-neoplastic agents are rare. Though the clinical presentations are overlapping, most IRs are not IgE-mediated allergic reactions. Appropriate premedication and slow rate of infusion facilitates uneventful administration of the anti-neoplastic agents in subsequent cycles. Further study in a larger cohort of patients to identify biomarkers of hypersensitivity is warranted.     

Disparity of amniotic fluid volume and fetal size: problem of the stuck twin--US studies

The "stuck twin" phenomenon in monochorionic diamniotic (MCDA) pregnancies is characterized by marked disparity in both fluid volume and fetal size between the twin gestations. To determine the prevalence, sonographic characteristics, and clinical outcome of this phenomenon, discharge summaries, placental pathologic reports, and prenatal sonograms from 307 twin pregnancies were reviewed. Of 52 cases of MCDA pregnancies, 18 (35%) demonstrated marked disparity in amniotic fluid volume. In 16 of these 18 cases there was discordant twin growth, further suggesting the diagnosis of twin transfusion syndrome. All 16 cases and an additional nine cases supplied by another center demonstrated a small, morphologically normal fetus in an oligohydramniotic sac suspended anteriorly (72%) or laterally (28%) in the uterus. The amniotic membrane separating this twin from the larger twin in the polyhydramniotic sac was thin, closely applied to the smaller fetus, and difficult to detect. Perinatal morbidity was 100% for all twin pairs, and premature labor occurred in all cases. Perinatal mortality ranged from 88% for the larger/poly twin to 96% for the small/oligo twin.     

Dentists'' and Physicians'' Attitudes on the Role of the Dental Health Care Team in a Cardiovascular Risk Factor Reduction Program

This study examines the attitudes of both dentists and physicians on the role of the dental health care team in a cardiovascular risk factor reduction program directed at a general "well" population. A questionnaire was sent to a stratified sample of primary care dentists and physicians in the Augusta, Georgia, metropolitan area. The questionnaire was divided into four parts: the demographic component and three attitude components (the affective component, the cognitive component, and the action component). Results showed that dentists tended to have a positive attitude about performing cholesterol screening, nutrition counseling, and blood pressure screening in the dental office. Physicians tended to be negative about the idea of dentists performing cholesterol screening and nutrition counseling and were undecided about this role for dentists in a cardiovascular risk factor reduction program. Both dentists and physicians had positive attitudes about the idea of dentists referring high cardiovascular risk patients to physicians, as well as about the role of dentists in blood pressure screening. Overall, although dentists and physicians expressed concerns about the role of dentists in a cardiovascular risk factor reduction program, responses of both groups demonstrated a willingness to explore this concept further.     

Neurological Dysfunction And Axonal Degeneration In Charcot-Marie-Tooth Disease Type 1A

More than 130 different mutations in the gap junction integral plasma membrane protein connexin32 (Cx32) have been linked to the human peripheral neuropathy X-linked Charcot-Marie-Tooth disease (CMTX). How these various mutants are processed by the cell and the mechanism(s) by which they cause CMTX are unknown. To address these issues, we have studied the intracellular transport, assembly, and degradation of three CMTX-linked Cx32 mutants stably expressed in PC12 cells. Each mutant had a distinct fate: E208K Cx32 appeared to be retained in the endoplasmic reticulum (ER), whereas both the E186K and R142W mutants were transported to perinuclear compartments from which they trafficked either to lysosomes (R142W Cx32) or back to the ER (E186K Cx32). Despite these differences, each mutant was soluble in nonionic detergent but unable to assemble into homomeric connexons. Degradation of both mutant and wild-type connexins was rapid (t(1/2) < 3 h) and took place at least in part in the ER by a process sensitive to proteasome inhibitors. The mutants studied are therefore unlikely to cause disease by accumulating in degradation-resistant aggregates but instead are efficiently cleared from the cell by quality control processes that prevent abnormal connexin molecules from traversing the secretory pathway.