肺癌患者外周血T淋巴细胞亚群变化及其临床意义

[目的]检测肺癌患者T淋巴细胞亚群变化.[方法]采用SAP法检测42例肺癌患者及20例正常对照组的外周血T淋巴细胞亚群,并将肺癌中转移组和未转移组分别与正常对照组进行比较.[结果](1)肺癌转移组CD3 、CD 4阳性率低于未转移组(P＜0.05),CD 4/CD 8比值比正常组及未转移组低(P＜0.05).(2)未转移组CD 8低于正常组及转移组(P＜0.05).[结论]肺癌患者细胞免疫功能低下,并且细胞免疫功能随病情进展逐步受到抑制.     

A Family Study of Autism: Cognitive Patterns and Levels in Parents and Siblings

First-degree relatives of 99 autism probands and of 36 Down's syndrome controls were assessed with standardised tests of intellectual functioning, reading, and spelling. Higher mean verbal IQ scores, and discrepancies in favour of verbal scores, were characteristic of autism relatives. No consistent differences were found on performance scales, reading, and spelling tests. Among autism relatives, siblings affected with the broad phenotype of autism had significantly lower IQ scores and poorer reading and spelling performances than unaffected siblings. However, the small size of the cognitive difference and the lack of a distinctive cognitive profile indicates that standardised cognitive measures used in this study are unlikely to improve the operationalised definition of the broad phenotype of autism. The slightly superior verbal performance of relatives in the autism group might represent some form of heterozygote advantage.     

Phenotypic shift in human differentiated gastric cancers from gastric to intestinal epithelial cell type during disease progression

Background. The phenotypic expression of tumor cells is widely thought to resemble that of the tissue of origin. In the present study, to assess phenotypic changes that occur with disease progression, we investigated human differentiated gastric cancers at different depths of invasion for component cancer cell types. Methods. Using a combined mucin histochemical and immunohistochemical approach, we classified surgical specimens of 301 differentiated gastric cancers into three types: gastric epithelial cell (G) type, intestinal epithelial cell (I) type and mixed gastric and intestinal (GI) type, according to the phenotypic differentiation of the component cancer cells. The relation between the phenotypic type of cancer and their depth of invasion was evaluated. Results. The proportion of G type cancers was 41.4% in early (tumor invasion of mucosa or submucosa) cases, decreasing to 22.2% in advanced (tumor invasion of muscularis propia or deeper) cases, whereas the proportion of I type cancers increased with progressive disease from 23.5% to 31.1% (P < 0.01). Cancers invading the subserosa or deeper included more I type cases and fewer G type than cancers limited to the mucosa (P < 0.01). In most cases of each phenotypic type, intestinal metaplasia was recognized in the surrounding background mucosa, but no clear relation was shown between the phenotype of cancers and the degree of intestinal metaplasia in the background mucosa, suggesting that intestinal metaplasia is not always a preneoplastic lesion. Conclusions. A phenotypic shift from G to I type expression was observed with the progression of human differentiated gastric cancers. Intestinalization may occur independently in cancerous and noncancerous gastric mucosa. Received for publication on May 1, 1998; accepted on Oct. 22, 1998     

细胞色素氧化酶CYP3A4基因突变与表型研究进展

细胞色素P4503A4在许多内源性及外源性化合物的氧化及还原代谢中起关键作用，对CYP3A4基因表达的研究具有重要意义。本文对CYP3A4基因突变及其表型特征加以总结。     

CHRNB3 is more strongly associated with Fagerström Test for Cigarette Dependence-based nicotine dependence than cigarettes per day: phenotype definition changes genome-wide association studies results

AIMS: Nicotine dependence is a highly heritable disorder associated with severe medical morbidity and mortality. Recent meta-analyses have found novel genetic loci associated with cigarettes per day (CPD), a proxy for nicotine dependence. The aim of this paper is to evaluate the importance of phenotype definition (i.e. CPD versus Fagerstr?m Test for Cigarette Dependence (FTCD) score as a measure of nicotine dependence) on genome-wide association studies of nicotine dependence. DESIGN: Genome-wide association study. SETTING: Community sample. PARTICIPANTS: A total of 3365 subjects who had smoked at least one cigarette were selected from the Study of Addiction: Genetics and Environment (SAGE). Of the participants, 2267 were European Americans, 999 were African Americans. MEASUREMENTS: Nicotine dependence defined by FTCD score ≥4, CPD. FINDINGS: The genetic locus most strongly associated with nicotine dependence was rs1451240 on chromosome 8 in the region of CHRNB3 [odds ratio (OR)?=?0.65, P?=?2.4?×?10(-8) ]. This association was further strengthened in a meta-analysis with a previously published data set (combined P?=?6.7?×?10(-16) , total n?=?4200). When CPD was used as an alternate phenotype, the association no longer reached genome-wide significance (β?=?-0.08, P?=?0.0004). CONCLUSIONS: Daily cigarette consumption and the Fagerstrom Test for Cigarette Dependence show different associations with polymorphisms in genetic loci.     

Behavioural phenotype of a patient with a de novo 1.2 Mb chromosome 4q25 microdeletion

A female patient, 20 years of age, is reported with a history characterized by developmental and psychomotor delay, and during grammar-school period increasing learning problems, ritualistic behaviours and social withdrawal. Subsequently, challenging and autistic-like behaviours became prominent. The patient showed mild facial dysmorphisms, long thin fingers with bilateral mild short V metacarpals, and hyperlaxity of the joints. Neuropsychiatric examination disclosed obsessive, ritualistic behaviours and vague ideas of reference. Neuropsychological assessment demonstrated mild intellectual disability, mental inflexibility and incongruent affect. MRI-scanning of the brain showed no relevant abnormalities. Genome wide SNP array analysis revealed a 1.2 Mb de novo interstitial microdeletion in 4q25 comprising 11 genes, that was considered to be causative for the developmental delay, perseverative cognitive phenotype and dysmorphisms.To the authors knowledge, this is the first report of a de novo 4q25 microdeletion that presents with a specific behavioural phenotype.     

Comparative features of Asthma with frequent or infrequent exacerbations: A longitudinal study of retrospective and prospective events

Background: A “frequent exacerbator phenotype” has been described, mostly in the population of patients with severe asthma. Further data are needed on such exacerbation-prone patients in milder asthma. Aim: To compare the characteristics of frequent and nonfrequent exacerbators in asthma of different severities and to assess the stability of the exacerbator status. Methods: This was an observational study comparing baseline data from frequent (≥2 exacerbations in the past year) and nonfrequent (<2 exacerbations in the past year) exacerbators. Patients were also followed up for one year. Information regarding clinical, physiologic, and inflammatory characteristics was collected at baseline and one-year follow-up. Results: Forty-seven frequent and 53 nonfrequent exacerbators were recruited. No specific clinical, physiologic, or inflammatory characteristic was observed in the frequent as compared to the nonfrequent exacerbators at baseline. Fifty-eight percent of patients reporting frequent exacerbations at baseline remained in this group after one year of follow-up. Forty-two and 62% of patients with, respectively, mild-to-moderate asthma and severe asthma had frequent exacerbations. In a post hoc analysis according to asthma severity, frequent exacerbators with severe asthma had a higher body mass index and poorer asthma control, although they reported higher adherence to medication, in comparison to frequent exacerbators with mild-to-moderate asthma. No specific characteristics could discriminate between frequent and nonfrequent exacerbators of the same asthma severity. Conclusions: Frequent exacerbators with severe asthma present some specific characteristics not observed in frequent exacerbators with mild-to-moderate disease. However, the latter group should be identified to reassess treatment needs and potential contributing factors.     

Broader autism phenotype as a risk factor for postpartum depression: Hamamatsu Birth Cohort (HBC) Study

The broader autism phenotype (BAP), which refers to the expression of behavioral and cognitive propensities that are milder but qualitatively similar to those defining autism spectrum disorder, can play a crucial role in postpartum depression (PPD). We investigated whether pregnant women's BAP would increase the risk for PPD, using a representative birth cohort in Japan. Pregnant women were enrolled in the Hamamatsu Birth Cohort (HBC) Study during their mid-gestation (N = 841) and were followed up until 3 months after delivery. BAP was measured mainly during the 2nd trimester of the pregnancy by using the Broader Phenotype Autism Symptoms Scale. Participants scoring 9 points or higher on the Edinburgh Postnatal Depression Scale at least once during the first 3 months after childbirth were diagnosed with PPD. Among participants, 128 (15.2%) women were found to have PPD. Multiple logistic regression analyses showed that BAP were associated with PPD (OR = 1.19, 95% CI [1.07–1.31]), even after controlling for other potential confounders. In addition, the association was not moderated by history of depression and/or anxiety disorders, including concurrent depressive and anxiety symptoms during pregnancy. The findings suggest that pregnant women with BAP have an elevated risk for PPD.