Rett syndrome from quintuple and triple deletions within the MECP2 deletion hotspot region

Rett syndrome results from mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene, which are nearly always lethal in males and lead to regression and reduced life expectancy in females. Herein we report one propositus with five tandem deletions and a second propositus with three tandem deletions within MECP2 exon 4 that encode truncated protein products resulting in classic Rett syndrome. These deletion breakpoints and single deletions in 3 other patients were all found within a 185-bp region along with 64 of 69 other reported deletion breakpoints in the MECP2 gene. Illegitimate recombination resulting in deletion at a substantial proportion of the shared MECP2 sites is enhanced by repeated guanosine (G) DNA sequences in the antisense direction, consistent with reports at other gene loci that polypurine (multiple guanosine or adenosine (A)) basepairs enhance sequence deletion. Multiple deletions at the same poly G recombination sites confirm the existence of deletion hotspots in this gene region with numerous repeated antisense sites that are enriched 26- to 161-fold. Deletion by illegitimate recombination within a single allele can occur during mitotic or meiotic cell cycles. Although prone to disease-causing deletion, this region is unique in humans and highly conserved among mammals for the last 75 000 000 years to maintain the MECP2 gene's critical function.     

Association between asthma and an intragenic variant of CC16 on chromosome 11q13

The β subunit of high affinity immunoglobulin E (IgE) receptor (FcɛRIβ) and the Clara cell derived inflammatory molecule, CC16 have been cited as candidate genes for atopic asthma on chromosome 11q13. A genetic association study was performed with an intragenic microsatellite repeat of CC16 gene on chromosome 11q12–13 in relation to atopic and non-atopic asthma. Whereas variants of FcɛRIβ at chromosome 11q13 show association with atopy and asthma, no significant association was found between asthma and CC16 genotypes irrespective of atopic status. These data support the candidacy of FcɛRIβ rather than CC16 for the atopic asthma locus on chromosome 11q.     

应用导数光谱法考察苯呋洛尔溶液体外经皮渗透性

本文应用二阶导数紫外分光光度法考察了苯呋洛尔溶液体外经皮渗透性。考察了促进剂月桂氮(?)酮-丙二醉及PEG-400溶剂对其渗透性的影响。应用二阶导数紫外分光光度法消除了兔皮溶出物对一般紫外测定方法的干扰。结果表明:苯呋洛尔溶液具有体外经皮渗透性;月桂氮(?)酮-丙二醇系统及PEG-400均能增强苯呋洛尔溶液的体外经皮渗透性。     

Chemopreventive effects of 2-(allylthio)pyrazine on hepatic lesion, mutagenesis and tumorigenesis induced by vinyl carbamate or vinyl carbamate epoxide

2-(Allylthio)pyrazine (2-AP), synthesized for its possible use as a hepatoprotective agent, has been found to selectively inhibit rat hepatic cytochrome P450 2E1 (Kim et al., Biochem. Pharmacol., 53, 261- 269, 1997), while it enhances the activities of phase II detoxification enzymes such as glutathione S-transferase and epoxide hydrolase. As part of a program in evaluating the chemopreventive potential of 2-AP, we have determined its effects on hepatotoxicity, mutagenicity and tumorigenicity of vinyl carbamate (VC), a prototypic hepatocarcinogen preferentially activated by P450 2E1 to the ultimate carcinogenic metabolite vinyl carbamate epoxide (VCO), which undergoes detoxification by glutathione conjugation and oxirane hydrolysis. Administration of 2-AP (100 mg/kg body wt) to male Sprague-Dawley rats by gavage, 2 days, 1 day and 4 h prior to VC or VCO, markedly ameliorated the hepatotoxicity of these compounds as determined by decreased serum aspartate aminotransferase and alanine aminotransferase activities. Furthermore, 2-AP pre-treatment significantly suppressed the VC-induced hepatocarcinogenesis in infant male B6C3F1 mice. In a separate experiment, the multiplicities of skin tumors formed in female ICR mice treated with 5.8 micromol of VC or VCO were inhibited 58 and 70%, respectively, by pre-treatment with 2-AP by oral administration. The mutational spectrum of ras-oncogene in papillomas was not altered by 2-AP pre-treatment. 2-AP also inhibited the mutagenicity of VC in the Salmonella-microsome assay. Taken together, these findings suggest that 2-AP is a potential chemopreventive agent.      

Current therapeutic uses and potential of β-adrenoceptor agonists and antagonists

β-Adrenoceptors are members of a large family of hormone and neurotransmitter receptors that initiate their biological function by coupling to GTP-binding regulatory proteins. β-Adrenoceptors can be subdivided into two main subgroups, designated β₁ and β₂. Atypical β-adrenoceptors or β₃-adrenoceptors, which are present on adipocytes, have been demonstrated pharmacologically. Their function in adipose tissue is currently being investigated. β₂-Adrenoceptor agonists have played a key role in the treatment of asthma for some 30 years, being used for the relief and prophylaxis of symptoms. There is, however, no evidence that tolerance to the bronchodilator or anti-bronchoconstrictor effects of these drugs is responsible for the deleterious effects reported with the regular use of bronchodilators. In neuropsychiatry, β-adrenoceptor antagonists have been used for the treatment of acute stress reactions and generalised anxiety, essential tremor and prophylaxis of migraine. In general, they are effective in anxiety disorders if the somatic symptoms are not extreme. For prophylactic treatment of migraine, β-adrenoceptor antagonists such as propranolol, metoprolol, nadolol and atenolol are the drugs of first choice. In cardiology, β-adrenoceptor antagonists are an important class for the treatment of high blood pressure, arrhythmias and angina pectoris, and for prevention of myocardial infarction. With chronic treatment, they reduce mortality in hypertension and prolong survival in patients with coronary heart disease. Received: 11 November 1996 / Accepted in revised form: 4 August 1997     

复方苍术消毒液对净化室空气的消毒效果观察

目的：考察复方苍术消毒液对净化室空气的消毒效果。方法：采用空气菌落自然沉降法,并与福尔马林消毒液及对照组比较。结果：消毒后空气菌落数符合GMP要求。结论：该法可适用于净化室的空气消毒。     

硝苯啶贴膜剂的研究

本文研究了硝苯啶骨架型贴膜剂经皮吸收的可行性。建立了测定体内和体外硝苯啶药物浓度的高液效相色谱法。两种处方的贴膜剂(R₁未加增渗剂,R₂加有月桂氮酮作为增渗剂)的体外经皮渗透实验表明:硝苯啶以零级动力学方式渗透皮肤,但在10.25 h前后释放速率不同,R₁分别为2.63及1.1μg/cm².h,R₂分别为4.30及1.5μg/cm²·h。由R₂贴膜剂的释放实验确定:硝苯啶从药库基质中的释放符合t~(1/2)型释放过程,释放速度常数为68.91μg/cm²·t^1/2。健康受试者五名贴用R₂贴膜剂1.5 h后达到稳态血浓,并在24.5h内保持治疗范围内的血药浓度(10～100 mg/ml),本文还对硝苯啶贴膜的质量进行了多方面的考察。     

Stage IB,IIA and proximal IIB,carcinoma of the uterine cervix,treated by irradiation alone or in combination with surgery

This is a report of a nonrandomized comparison of treatment results of 139 patients with stage IB, IIA and proximal IIB carcinoma of the uterine cervix treated by radiation alone and 113 treated with a combination of radiation and surgery. The five-year tumor free acturial survival for the patients with stage IB either with irradiation alone (RT) or combined with surgery (RS) was approximately 87%. For stage II the tumor free actuarial five-year survival 79% with patients of RS, and 76% with RT. In the 113 patients treated with RS there were 18 (16%). In the 139 patients treated by RT there were 18 (13%) recurrences of pelvic, 4 local recurrences, 11 combined with parametrial, and free parametrial recurrences. There was no significant difference in the survival and recurrence rate of the patients treated with either method. Major complications were comparable in both groups (RT approximately 25% and RS approximately 10%), but 2/3 of those complications recovered without sequelae. The most frequent minor complication in the patients treated with RT was rectosigmoiditis.     

A rapid screening test for detection of IgA deficiency

A solid-phase red cell adherence (SPRCA) assay has been developed to screen blood donors for IgA deficiency, and 6117 donor sera have been screened by this method. Eighteen sera were found to be IgA deficient, which represents a frequency of 1 in 340. Seventeen of these sera were retested by passive hemagglutination inhibition, which has a sensitivity of approximately 0.1 mg per dL. Eight sera were confirmed as IgA deficient, and nine were found to contain low levels of IgA (less than 1 mg/dL). The approximate sensitivity of the SPRCA assay is 1 mg per dL. The speed, simplicity, and sensitivity of this assay make it a good alternative to conventional methods of screening.