Homozygous deletions of the p15 (MTS2) and p16 (CDKN2/MTS1) genes in adult T-cell leukemia

Adult T-cell leukemia (ATL) is associated with prior infection with human T-cell leukemia virus type I (HTLV-I). Twenty to 40 years often elapse from viral infection to overt ATL, suggesting that other genetic events must occur to produce frank leukemia. The p15 (MTS2) and p16 (CDKN2/MTS1) genes located on chromosome 9p have been implicated as candidate tumor-suppressor genes in several types of tumors. We examined for alterations of these genes in ATL using Southern blot and polymerase chain reaction-single-strand conformation polymorphism analyses. Both p15 and p16 genes were homozygously deleted in 4 of 23 acute/lymphomatous ATL (17%). An additional 3 (13%) and 4 (17%) acute/lymphomatous samples had hemizygous deletions in at least one exon of p15 and p16, respectively. One of 14 chronic ATL samples had a homozygously deleted p16 gene and another had a hemizygous deletion of p16. Neither homozygous nor hemizygous deletions of the p15 gene were found in chronic ATL. In total, 10 of 37 (27%) ATL samples had loss of the p15 and/or p16 genes. No point mutations of the p15 and p16 genes were found. The ATL patient with a homozygously deleted p16 in the chronic phase rapidly progressed to acute ATL and died within 6 months of the initial diagnosis. One instructive patient had no detectable deletion of the p15 and p16 genes during the chronic phase of ATL but had a homozygous deletions of both genes when she progressed to acute ATL. Our results suggest an association of p15/p16 deletions with development of acute ATL.     

The Health Status Questionnaire: achieving concordance with published disability criteria

AIM: To compare the Health Status Questionnaire with established methods of assessing disability in preterm and very low birthweight infants. METHOD: All survivors of gestational age <31 weeks or birth weight <1500 g, born in 1994 to women resident in Wales were identified. Assessments were by a single observer at a median corrected age of 28.3 months and included the Health Status Questionnaire and a Griffiths developmental test. Outcome was also described according to criteria for disability used in three published studies. RESULTS: There were 297 survivors of which 279 (94%) were assessed. Using the Health Status Questionnaire, severe disability was found in 12.9% of cases compared to 8.2%, 2.9%, and 3.6% using the Northern, Victorian, and Mersey outcome criteria respectively. Following the simple modifications of removing the growth criteria from the Health Status Questionnaire and reclassifying the severe disability group in the Victorian and Mersey criteria, comparable severe disability rates ranging from 7.9% to 9.3% were found. CONCLUSION: The Health Status Questionnaire requires no formal training, is rapid to perform, and with simple modifications provides comparable results to established methods of assessing disability. Its use in the follow up of preterm and very low birthweight infants should be encouraged.     

Structure, function, and degeneration of bovine hyaline cartilage: assessment with MR imaging in vitro

The basic magnetic resonance (MR) imaging pattern of normal and degenerated hyaline articular cartilage was studied in vitro in 40 fresh bovine patellae. With the use of an ample spectrum of strongly T1- to T2-weighted sequences, two zones of cartilage with different signal intensities were observed in all specimens. A superficial cartilaginous layer in the MR image with higher water content and longer T1 and T2 correlated with the tangential and transitional zones of normal articular cartilage, whereas a second MR imaging zone with shorter T1 and T2 was identified in the depth of the articular cartilage. Different functional properties in pressure resistance were observed in the two layers. In early cartilage degeneration without thinning, there was increased hydration of the superficial cartilage layer. This study suggests that strongly T1- and T2-weighted images are indispensable for evaluating details in articular cartilage degeneration.     

Low total protein S antigen but high protein S activity due to decreased C4b-binding protein in neonates

Protein S, a vitamin K-dependent cofactor for activated protein C, exists in normal adult plasma in a free anticoagulantly active form and in an inactive form complexed to C4b-binding protein. Immunologic and functional levels of protein S and C4b-binding protein in plasma were determined for 20 newborn infants and compared with adult normal pooled plasma. Total protein S antigen levels averaged 23%, similar to other vitamin K-dependent plasma proteins. However, the protein S anticoagulant activity was 74% of that of adult normal plasma. This apparent discrepancy of activity to antigen was shown to be due to low or undetectable levels of C4b-binding protein, which results in the presence of most if not all of protein S in its free and active form. The relatively high level of anticoagulantly active protein S in infants may enhance the potential of the protein C pathway, thereby minimizing risks of venous thrombosis in this group.     

The four-and-a-half-LIM protein 2 （FHL2） is overexpressed in gliomas and associated with oncogenic activities

Four-and-a-half-LIM protein 2 （FHL2） is a member of FHL protein family, which plays a crucial role in regulating gene expression, cell survival, and migration.Ahhough its function in oncogenesis appears to be tumor type-specific, its roles in glioma formation and development are yet to be elucidated. In the present study, we demonstrated that the mRNA level of FHL2 was elevated in both low- and high-grade glioma samples.     

Transanal endoscopic microsurgery for correction of rectourethral fistulae

BACKGROUND: Rectourethral fistula is a rare complication of radical prostatectomy. Transanal endoscopic microsurgery (TEM) is a minimally invasive technique available for its surgical correction, although currently, TEM is used more commonly for excision of adenomas and stage T(1) carcinomas of the rectum. PATIENTS AND METHODS: We report two patients with rectourethral fistulae after laparoscopic radical prostatectomy in whom TEM was used for closure. The surgical procedure included microscopic full-thickness excision of the rectal wall around the fistula with a 1-cm margin and endoscopic suturing of the defect in the urethral and rectal walls. RESULTS: In one case, the rectourethral fistula was closed using TEM. In the other patient, the procedure, performed after failure of a graciloplasty, was difficult because of extensive scar tissue, and the fistula persisted. CONCLUSIONS: The TEM procedure is a minimally invasive technique that may be considered for surgical repair of rectourethral fistulae.     

Smoking cessation at the workplace: 1 year success of short seminars

Objectives: In search of less time-consuming methods of smoking cessation Allen Carr’ seminars performed at workplaces in Austria were evaluated. Methods: Of all the 357 smokers attending a seminar in summer 2002, 308 (86%), consented to participate in a repeated health survey, including the SF-36 questionnaire. After 3 months 268 (87%) gave computer-aided telephone interviews and 223 (72%) after 1 year. Analysis by logistic regression was done separately for males and females. Results: The 1-year quit rate was 40% (worst case assumption) to 55% (best estimate). In 96% of quitters an intensive counseling for 6 h without pharmaceutical aid thereafter was sufficient to maintain abstinence for 12 months. A long smoking history or many earlier unsuccessful attempts to quit did not predict failure. The risk of relapse was found higher in young men with a high number of pack-years and in women with good physical fitness but high Fagerstroem score and financial reasons for the intention to quit smoking. While an average weight gain of 3 kg in males was not associated with failure to quit smoking, we found the highest weight gain (4 kg) in females in the group abstinent at 3 months but smoking again at 12 months. In all participants subjective life quality scored by SF-36 improved. In quitters perception of general health improved more. Conclusions: Group counseling at the workplace was found to be an efficient method of smoking cessation, capable of increasing subjective life quality and health and to smooth the way to smoke-free enterprises. The Corresponding Author has the right to grant on behalf of all authors and does grant on behalf of all authors, an exclusive license on a worldwide basis to permit this article (if accepted) to be published in Int Arch Occup Environ Health.     

An unusual pattern of mutation in the duplicated portion of PKD1 is revealed by use of a novel strategy for mutation detection

The gene for the most common and severe form of autosomal dominant polycystic kidney disease, PKD1, encodes a 14 kb mRNA that is predicted to result in an integral membrane protein of 4302 amino acids. The major challenge faced by researchers attempting to complete mutation analysis of the PKD1 gene has been the presence of several homologous loci also located on chromosome 16. Because the sequence of PKD1 and its homologs is nearly identical in the 5' region of the gene, most traditional approaches to mutation analysis cannot distinguish sequence variants occurring uniquely in PKD1. Therefore, only a small number of mutations have been identified to date and these have all been found in the 3', unique portion of the gene. In order to begin analysis of the duplicated region of PKD1, we have devised a novel strategy that depends on long-range PCR and a single gene-specific primer from the unique region of the gene to amplify a PKD1-specific template that spans exons 23-34. This 10 kb template, amplified from genomic DNA, can be employed for mutation analysis using a wide variety of sequence- based approaches. We have used our long-range PCR strategy to begin screening for sequence variants with heteroduplex analysis, and several affected individuals were discovered to have clusters of base pair substitutions in exons 23 and 25. In two patients, these changes, identified in exon 23, would be predicted to result in multiple amino acid substitutions in a short stretch of the protein. This clustering of base pair substitutions is unusual and suggests that mutation may result from unique structural features of the PKD1 gene.      

小儿热感宁口服液的解热作用研究

观察小儿热感宁口服液的解热作用,并探讨其处方的合理性。方法：２,４－二硝基苯酚所致热的大鼠发热试验。结果：大鼠灌胃ＸＲＫ２５ｍｌ／ｋｇ后０．５,１和１．５ｈ时可显著抑制大鼠的体温升高;其组份牛磺酸和葛根提取物均有抑制大鼠体温升高的趋势,但差异不显著,说明该两组份有解热协同作用。