The factor V leiden mutation and the risk of venous thromboembolism in gynecologic oncology patients1

OBJECTIVE: To measure the strength of the association between the factor V Leiden mutation and venous thromboembolism in gynecologic oncology patients. METHODS: We conducted a case-control study of gynecologic cancer patients in a referral center who were group matched for demographics, tumor type, and treatment. The prevalence of the factor V Leiden mutation was determined in both cases and controls, and an odds ratio was calculated. The factor V Leiden mutation was detected using polymerase chain reaction amplification and nucleic acid restriction digest of deoxyribonucleic acid extracted from leukocytes. RESULTS: Seventy-five patients were enrolled in the study. Seventy-four samples were available for analysis. There were no differences between the cases and controls with respect to age, race, body mass index, smoking, cancer type, high stage (III or IV) of cancer, or treatment modality. The odds ratio for having the factor V Leiden mutation in patients with venous thromboembolism was 0.3 (95% confidence interval 0.1, 1.7). CONCLUSION: This study suggests that the factor V Leiden mutation is not associated with an increased risk of venous thromboembolism in gynecologic oncology patients. This contrasts with other studies showing a strong association between the factor V Leiden mutation and venous thromboembolism in cases of previously unexplained venous thromboembolism, and venous thromboembolism associated with other hypercoagulable states, such as pregnancy and oral contraceptive use. The risk of venous thromboembolism due to cancer outweighs the contribution of the factor V Leiden mutation.     

A 25-Year analysis of deaths from uterine cancer in Louisville,Kentucky

Mortality rates for carcinoma of the cervix and for other malignant neoplasms of the uterus including other and unspecified parts were reviewed over a 25-year period, 1953–1977. The official death certification of each patient was checked against the patient records in the Louisville Uterine Cancer Registry. Errors were found in assigning residency status, inappropriate coding of cervix cancer as uterus other than cervix, and vice versa, attributing deaths from other cancer to uterus or cervix and to assigning deaths to a uterine site in cases known not to have cancer by virtue of autopsy or prior hysterectomy. The errors often counterbalanced and tended to decrease with time, nonetheless they were significant. After correction, the death rates from cervix cancer had declined by 52.3% for residents of Louisville, Jefferson County, Kentucky, over the 25-year period. This is attributed to a mass population screening program initiated in 1956, since a mortality decrease over a similar time period has never been documented in an unscreened population.     

Extracellular ATP-dependent suppression of proliferation and induction of differentiation of human HL-60 leukemia cells by distinct mechanisms

Extracellular ATP suppressed the growth of HL-60 leukemia cells and induced their differentiation as revealed by N-formyl-methionyl-leucyl-phenylalanine-induced beta-glucuronidase release. ATP degraded to ADP, AMP, and adenosine, and the effect of ATP on cell growth was mimicked by these metabolites added to the cultures. The stable analog alpha,beta-methylene ATP, however, had only a weak inhibitory effect on cell growth. Adenine nucleotide-induced growth suppression was reversed by uridine, suggesting the involvement of intracellular pyrimidine starvation secondary to adenosine accumulation. Consistent with this, ATP induced intracellular starvation of pyrimidine nucleotides, and this effect was also prevented by pretreatment of cells with uridine. The order of effectiveness of ATP-induced differentiation of HL-60 cells, unlike that for growth suppression, was ATP > ADP > AMP, and adenosine had no effect. Furthermore, uridine had no effect and the stable analog, alpha,beta-methylene ATP also induced HL-60 cell differentiation, suggesting that differentiation was due to ATP per se. We tested the hypothesis that ATP-induced differentiation arises from activation of adenylyl cyclase by the novel P2Y(11) receptor using the cell-permeable inhibitor of protein kinase A, Rp-CPT-cAMPS (8-(4-chlorophenylthio)adenosine-3',5'-cyclic monophosphorothioate, Rp isomer). Rp-CPT-cAMPS (1-100 microM) prevented ATP-induced differentiation of HL-60 cells as assessed by fMLP-induced beta-glucuronidase release. However, Rp-CPT-cAMPS did not prevent ATP-induced growth suppression. Taken together, the data indicate that extracellular ATP suppresses HL-60 growth and induces their differentiation by distinct mechanisms. Growth suppression arises from adenosine generation and consequent pyrimidine starvation. Differentiation arises, at least in part, from a distinct mechanism involving the activation of cell surface P2 receptors coupled to cAMP generation and activation of protein kinase A.     

Evidence of mitochondrial dysfunction in obese adolescents

Aim: Although obesity and weight gain generally are anticipated to be caused by an imbalance between energy intake and energy expenditure, the significance of thyroid hormones (TH) remains unclear. Examination of mitochondrial function may reflect intracellular thyroid hormone effect and elucidate whether a lower metabolic rate is present. Methods: In a group of 34 obese adolescents (age <16 years and body mass index above the age‐related 95th percentile), and an age‐ and gender‐matched group of 32 lean adolescent, thyroid stimulating hormone (TSH) and basal oxygen consumption were measured and mitochondrial function in peripheral blood monocytes was determined by flow cytometry. Results: Significant increase in TSH (3.06 ± 1.56 mU/L vs. 2.33 ± 0.91 mU/L, p < 0.05) and a decrease in VO₂ (129 ± 16 mL O₂/m²*min vs. 146 ± 15 mL O₂/m²*min, p < 0.05) were observed in obese adolescents compared with lean adolescents. Flow cytometry analysis demonstrated a lower mitochondrial mass (6385 ± 1962 a.u. vs. 7608 ± 2328 a.u., p < 0.05) and mitochondrial membrane potential (11426 ± 3861 a.u. vs. 14017 ± 5536 a.u., p < 0.05) in obese adolescents compared with lean adolescents. These results are even more pronounced in adolescents with obese mothers. Conclusion: In obese adolescents, the increased TSH and lowered VO₂ propose a lowered basal metabolic rate and the impaired mitochondrial function suggests a decreased thyroid hormone stimulation of mitochondrial energy production. The maternal in‐heritage is suggestive of a basal metabolic defect or mitochondrial resistance for TH.     

Endothelial chemokines in autoimmune disease

Compelling evidence now exists supporting the involvement of chemokines in the pathogenesis of autoimmune diseases. Examples of chemokines and chemokine receptors being involved in mediating autoimmune disease exist for rheumatoid arthritis, multiple sclerosis, allograft rejection, systemic lupus erythematosus, psoriasis, atopic dermatitis, lichen planus, and graft-versus-host-disease. Expression of chemokines by endothelial cells appears to be an important step in the development of these diseases. Since chemokines are small molecular weight molecules that act through G-protein coupled receptors, they make attractive drug targets. Several antagonists of chemokine - chemokine receptor interactions have been used to successfully alleviate some or all of the symptoms associated with many of these diseases in animal models. Further investigation of the involvement of chemokines in the pathogenesis or progression of autoimmune diseases may lead to practical clinical advances in diagnosis, prognosis, and therapy of such diseases.     

Morphological changes due to Lead exposure and the influence of DMSA on the gill tissues of the freshwater fish, Catla catla

Catla catla fingerlings were reared in freshwater and exposed to 15.5 ppm concentration of lead for 60 days. The morphological changes on the gill of the C. catla fingerlings due to lead intoxication and the effect of DMSA (meso 2,3-dimercaptosuccinic acid) on the affected tissues were observed using Scanning Electron Microscope. It has been found that the lead treated gill tissues showed certain marked changes, such as cell hypertrophy, alteration in the lamellar surfaces, epithelial hyperplasia and the fusion of adjacent lamellae. The antidote DMSA treatment reduces the toxic effects and helps the recovery of gill tissue and its return to the level of the control/normal.     

人亲环素A基因克隆及在大肠杆菌中表达

目的 :用基因重组技术表达人亲环素 A( Cy PA) ,以避免从人组织材料中提取纯化该蛋白的麻烦。　 方法 :应用反转录聚合酶链反应 ( RT- PCR)技术从人淋巴细胞系 ( MT4 )总 RNA中扩增得到 Cy PA基因片段 ,并用重组 DNA技术对该基因片段进行克隆 ,构建表达载体 ,转入大肠杆菌进行表达。　 结果 :DNA序列分析表明 ,得到的基因片段与设计编码 Cy PA的结构基因序列完全相同。所构建的表达载体 p ET11/Cy PA转入大肠杆菌获得表达 ,重组蛋白表达量占菌体可溶性蛋白的 4 1% ,经测定具有肽基脯氨酸顺 /反异构酶活性。　 结论 :利用基因重组技术使大肠杆菌高效表达出有生物活性的人 Cy PA。     

HIV mediates a productive infection of the brain.

BACKGROUND: Approximately one quarter of patients with AIDS develop severe cognitive deficits called HIV-associated dementia complex. There is some controversy regarding the importance of viral load and distribution in mediating this neurologic disease. OBJECTIVE: Brain HIV proviral and RNA loads were compared to define the molecular nature of HIV infection of the brain. METHOD: Neuropathologic examination was performed on brains from 10 autopsies of patients with AIDS that had short post-mortem intervals and no evidence of opportunistic infection. Viral DNA and RNA were extracted and quantified from multiple brain regions. These findings were compared with triple-label immunofluorescence for viral and cell markers. RESULTS: Brains with histopathologic evidence of HIV encephalitis contained abundant HIV RNA and DNA. Regions without productive HIV infection showed minimal proviral load. By immunocytochemistry, only brain macrophages/microglia double labeled for viral proteins. CONCLUSIONS: HIV mediates a productive infection of brain macrophages/microglia. There was no evidence supporting the hypothesis of substantial neuronal or macroglial infection, or evidence of substantial proviral burden prior to the development of productive infection.