Assessment of bioequivalence after subcutaneous and intramuscular administration of urinary gonadotrophins

The objective was to demonstrate bioequivalence between s.c. and i.m. administration of Humegon (FSH/LH ratio 1:1) and Normegon (FSH/LH ratio 3:1). In two randomized, single-centre, cross-over studies, 18 healthy volunteers on each formulation were assigned to one of the two administration sequences. Subjects were given single doses of one of the above gonadotrophins after endogenous gonadotrophin production had first been suppressed using high-dose oral contraceptive. Subsequently, rate (Cmax, tmax) and extent (AUC) of absorption of follicle stimulating hormone (FSH) and luteinizing hormone (LH) were determined for 14 days. For Cmax and AUC, analysis of variance (ANOVA) was performed on log-transformed data and for tmax ANOVA was performed on ranks. Intramuscular and s.c. injections of Humegon were bioequivalent with respect to the main pharmacokinetic parameters, being AUC and Cmax of FSH absorption. Intramuscular and s.c. injections of Normegon were bioequivalent with respect to the AUC of FSH and not bioequivalent with respect to the Cmax of FSH. For tmax of FSH as well as for most LH variables of both preparations, bioequivalence could not be proven due to the high intra- and interindividual variability and/or concentrations being close to the detection limit. Thus, the main pharmacokinetic FSH variables after i.m. and s.c. administration of Humegon and Normegon were bioequivalent.      

Rapid detection of beta-globin gene (HBB) mutations coupling heteroduplex and primer-extension analysis by DHPLC

Beta-thalassemia is a common inherited disease, resulting from one or more of a total of more than 200 different mutations in the beta-globin gene (HBB). Efficient and reliable mutation-screening methods are essential in order to establish appropriate prevention programs for at-risk populations based upon a molecular diagnosis. We have developed a rapid and highly-specific mutation screening test for the diagnosis of beta-thalassemia by coupling heteroduplex and primer-extension analysis based on the denaturing high performance liquid chromatography (DHPLC) system. A total of 161 healthy heterozygous Taiwanese carriers featuring 10 different HBB mutations and 30 patients exhibiting 12 different compound heterozygous or homozygous HBB mutations were subjected to DHPLC. The elution profile for the heteroduplex analysis of DHPLC could be successfully used to identify the common disease-causing mutations of HBB. To further confirm the sequence variants, we developed a technique combining multiplex primer-extension analysis coupled with DHPLC for the genotyping of eight common disease-causing mutations in the HBB gene. Overall, by coupling heteroduplex and primer-extension analysis based upon DHPLC, we were able to unambiguously identify the most-common beta-thalassemia mutations corresponding to more than 99% of HBB alleles among the Taiwanese population. In conclusion, compared to classic approaches to mutation screening for this malady, we suggest that DHPLC is an excellent technique to be applied to the genetic screening of prenatal and postnatal individuals as a part of a diagnosis program for beta-thalassemia and provides a more-efficient, economic, and sensitive means to undertake such a screening program.     

Lupus-related advanced liver involvement as the initial presentation of systemic lupus erythematosus.

BACKGROUND AND PURPOSE: Systemic lupus erythematosus (SLE), a prototype of systemic autoimmune disease characterized by multiorgan involvement with diverse clinical and serological manifestations, principally affects women in their child-bearing years. Clinically significant hepatic abnormality as the initial presentation of SLE has rarely been reported. METHODS: Eleven patients with lupus with initial presentation of lupus-related hepatitis were included in this retrospective review. Clinical manifestation, immunological profiles, and risk factors for poor prognosis were analyzed. RESULTS: The most commonly associated clinical manifestations were found to be thrombocytopenia, leukopenia, advancing age, and presence of anti-SSA/Ro antibody and anti-thyroid antibodies. The diagnosis of SLE was delayed due to dominant hepatic abnormalities. Age greater than 50 years and marked hepatic decompensation in accordance with Child classification B and C might suggest poor prognosis (p=0.06). However, the p value was not statistically significant because of the small sample size. CONCLUSIONS: Lupus-related hepatitis, particularly in late-onset lupus, is common. In addition, the presence of anti-SSA, anti-thyroglobulin, and anti-microsomal antibodies is indicative of hepatic involvement in patients with SLE.     

Decreased production of CD8 (T8) antigen after immunotherapy

The working mechanism(s) of immunotherapy still remains ill defined. As T cells bearing CD8 antigen possess suppressor/cytotoxic function, this study was conducted to examine the effect of immunotherapy on the production of CD8 antigen. Peripheral blood mononuclear cells (MNC) were obtained from 21 newly diagnosed and 23 hyposensitized (>1 year) asthmatic children and 13 agematched normal children. MNC were stimulated with crude mite extract (Dermatophagoides farinae) for 7 days and with phytohemagglutinin and concanavalin A for 3 days. The CD8 antigen and interleukin-2 receptor (IL-2R) in plasmas and culture supernatants were measured by CELLFREE T8 and IL-2R test kits (T Cell Sciences, USA). The results showed the following. (1) Plasma CD8 antigen was markedly increased in new patients compared to normals (536.7 ± 212.3 vs 222.5 ± 104.0 units/ml;P<0.001) and decreased to normal after immunotherapy (275.7 ± 98.5 units/ml). (2) When stimulated with mite allergen, MNC from both new and hyposensitized patients produced a much greater amount of CD8 antigen compared to those from normals. However, after immunotherapy MNC tended to produce less CD8 antigen, although not to a significant degree. (3) No difference in CD8 antigen production was seen among three groups when lymphocytes were stimulated with mitogens. (4) Production of CD8 antigen paralleled that of IL-2R. Thus, CD8 production was specifically decreased after immunotherapy and this fact reflects a hyposensitized state of T cells after long-term, repeated injection of allergens.     

四川参叶的生药学鉴定研究

参叶为少常用中药,主产于四川。我们通过调查,发現四川药用的参叶共有8种,均属人参属植物。本文报道了对8种参叶的生药学鉴定研究结果,提出了它们之间性状、显微特征的异同,创设了表皮细胞数的概念,并肯定了它在生药鉴定中的价值。研究结果对于合理用药、开发利用人参属植物资源及人参属植物的分类均有一定的价值。     

Two-stage Study of Familial Prostate Cancer by Whole-exome Sequencing and Custom Capture Identifies 10 Novel Genes Associated with the Risk of Prostate Cancer

BackgroundFamily history of prostate cancer (PCa) is a well-known risk factor, and both common and rare genetic variants are associated with the disease.ObjectiveTo detect new genetic variants associated with PCa, capitalizing on the role of family history and more aggressive PCa.Design, setting, and participantsA two-stage design was used. In stage one, whole-exome sequencing was used to identify potential risk alleles among affected men with a strong family history of disease or with more aggressive disease (491 cases and 429 controls). Aggressive disease was based on a sum of scores for Gleason score, node status, metastasis, tumor stage, prostate-specific antigen at diagnosis, systemic recurrence, and time to PCa death. Genes identified in stage one were screened in stage two using a custom-capture design in an independent set of 2917 cases and 1899 controls.Outcome measurements and statistical analysisFrequencies of genetic variants (singly or jointly in a gene) were compared between cases and controls.Results and limitationsEleven genes previously reported to be associated with PCa were detected (ATM, BRCA2, HOXB13, FAM111A, EMSY, HNF1B, KLK3, MSMB, PCAT1, PRSS3, and TERT), as well as an additional 10 novel genes (PABPC1, QK1, FAM114A1, MUC6, MYCBP2, RAPGEF4, RNASEH2B, ULK4, XPO7, and THAP3). Of these 10 novel genes, all but PABPC1 and ULK4 were primarily associated with the risk of aggressive PCa.ConclusionsOur approach demonstrates the advantage of gene sequencing in the search for genetic variants associated with PCa and the benefits of sampling patients with a strong family history of disease or an aggressive form of disease.Patient summaryMultiple genes are associated with prostate cancer (PCa) among men with a strong family history of this disease or among men with an aggressive form of PCa.     

Differential expression and regulation of p53 in human prostatic cells

Although genetic analysis has convincingly shown the association possibly existing between alterations in p53 tumor suppressor gene and a broad spectrum of human tumors including prostate cancer, surprisingly little is known about ways in which p53 at the protein level is controlled. To determine factors that may play a role in its regulation and expression, changes in p53 protein was investigated by using the androgen-insensitive JCA-1, DU-145, PC-3 and the androgen-responsive LNCaP cells. With the exception of PC-3 cells in which p53 is missing, multiple distinct forms of p53 were found in the other 3 prostate cell lines. A single p53 band was detected in the JCA-1 cell extracts, whereas two and three p53 immunoreactive bands were correspondingly observed in the DU-145 and LNCaP cells. The relative abundance and distribution of the different forms of p53 in the latter two cell types varied with proliferation of cells in culture. In the presence of charcoal-stripped fetal bovine serum (cFBS), LNCaP took on the morphology of neuroendocrine cells, a phenotypic change which was accompanied by a greater than 80% reduction in p53 expression, concurrent with elimination of the two slow migrating forms of p53. Induction of apoptosis in JCA-1 cells by treatment with the retinoid 4-HPR caused the virtual disappearance of p53, which coincided with specific processing of p53 into lower molecular weight 28 kD fragments. We propose that rapid and dynamic posttranslational changes in p53 may actively participate in determining mutually exclusive functional cellular events such as proliferation, differentiation, and apoptosis.     

Increasing nosocomial infections of methicillin-resistant Staphylococcus aureus at a teaching hospital in Taiwan

Methicillin-resistant Staphylococcus aureus (MRSA) is a worldwide important pathogen in nosocomial infections. To investigate the extent of the problem in Taiwan, analysis for the period of 1981-1994 was carried out of prospective surveillance data from the National Taiwan University Hospital, a major university teaching hospital in Taiwan. The number of nosocomial MRSA infections increased from five in 1981 to 133 in 1994, and the incidence increased from 0.2 episodes/1000 discharges in 1981 to 2.9 episodes/1000 discharges in 1994. The most common infection site was surgical wounds, which accounted for 26.3% of total 577 episodes of nosocomial MRSA infections during the study period. However, bacteraemia has become more and more common during the past 14 years. MRSA infections occured more frequently in patients stayed in the burn unit and other intensive care units than in the general wards. Other than oxacillin, the resistance rate to many other antibiotics also increased in S. aureus strains causing nosocomial infections in this hospital. Vancomycin remained active to all these S. aureus strains, even until 1994.     

Marital role attitudes and expected role behaviors of college youth in mainland China and Taiwan

Mainland China and Taiwan have been politically and physically segregated since 1949, and it was not until the late 1980s that limited contacts and cultural exchanges between the two societies began to take place. During their period of segregation, the two societies adopted different approaches toward gender roles. While gender equality was actively promoted in mainland China, the government in Taiwan lacked the theoretical guidance on how to achieve such equality. Gender egalitarianism in Taiwan therefore remains at the abstract or philosophical level with no specification of what gender equality means in concrete terms. Testing the hypothesis that people in mainland China have become more egalitarian than have people in Taiwan with respect to the division of marital roles, the authors investigated the differences in marital role attitudes and expected behavior among selected college students in mainland China and Taiwan. Survey responses were obtained from 185 male and 154 female students from Taiwan and 150 male and 138 female students from mainland China of different years and majors on four dimensions of marital role attitudes and six areas of traditional husband and wife role behaviors. The dimensions were determined through exploratory and confirmatory factor analyses. The data indicate that although most of the hypothesized societal differences are supported, some are not. The authors speculate that possible regressive changes in mainland China and progressive changes in Taiwan during the past decade were responsible for the discrepancy between hypotheses and results.