Comparative study of active site structure in bovine and Pacific salmon trypsins

The kinetic investigation was carried out on the inhibition of hydrolysis of N, alpha-benzoyl-D, L-arginine-p-nitroanilide (BApNA) for bovine and salmon trypsin by phenylmethanesulphonyl fluoride (PMSF), N, alpha-tosyl-L-lysine chloromethyl ketone (N-TLCK), N, alpha-tosyl-L-phenylalanine chloromethyl ketone (N-TPCK). Kinetic parameters of inhibition (Ki, k2) by PMSF for salmon and bovine trypsin differ insignificantly. The k2/Ki value of N-TPCK for salmon trypsin is 10 times more than of bovine trypsin. Kinetic parameters of inhibition by N-TLCK had the less difference. The Ki value of this inhibitor for salmon trypsin is 5 times less than that of bovine trypsin and k2 value is 1.7 times less.     

21世纪的耐火材料——动态高技术复合材料

从高技术复合材料的发展前景阐述了钙铝酸盐水泥结合浇注料和MgO-C砖这两类现代耐火材料。这些材料不仅是典型的尖端多相复合材料,而且显示了其他复合材料中难以见到的动态特性。讨论了产生这一特性的某些动力学因素。得到的结论是:当用复合材料这个术语描述这些耐火材料的某些方面时,动态特性又增加了一层复杂性。     

Five versus more than five years of tamoxifen therapy for breast cancer patients with negative lymph nodes and estrogen receptor-positive tumors

BACKGROUND: In 1982, the National Surgical Adjuvant Breast and Bowel Project initiated a randomized, double-blinded, placebo-controlled trial (B-14) to determine the effectiveness of adjuvant tamoxifen therapy in patients with primary operable breast cancer who had estrogen receptor-positive tumors and no axillary lymph node involvement. The findings indicated that tamoxifen therapy provided substantial benefit to patients with early stage disease. However, questions arose about how long the observed benefit would persist, about the duration of therapy necessary to maintain maximum benefit, and about the nature and severity of adverse effects from prolonged treatment. PURPOSE: We evaluated the outcome of patients in the B-14 trial through 10 years of follow-up. In addition, the effects of 5 years versus more than 5 years of tamoxifen therapy were compared. METHODS: In the trial, patients were initially assigned to receive either tamoxifen at 20 mg/day (n = 1404) or placebo (n = 1414). Tamoxifen-treated patients who remained disease free after 5 years of therapy were then reassigned to receive either another 5 years of tamoxifen (n = 322) or 5 years of placebo (n = 321). After the study began, another group of patients who met the same protocol eligibility requirements as the randomly assigned patients were registered to receive tamoxifen (n = 1211). Registered patients who were disease free after 5 years of treatment were also randomly assigned to another 5 years of tamoxifen (n = 261) or to 5 years of placebo (n = 249). To compare 5 years with more than 5 years of tamoxifen therapy, data relating to all patients reassigned to an additional 5 years of the drug were combined. Patients who were not reassigned to either tamoxifen or placebo continued to be followed in the study. Survival, disease-free survival, and distant disease-free survival (relating to failure at distant sites) were estimated by use of the Kaplan-Meier method; differences between the treatment groups were assessed by use of the logrank test. The relative risks of failure (with 95% confidence intervals [CIs]) were determined by use of the Cox proportional hazards model. Reported P values are two-sided. RESULTS: Through 10 years of follow-up, a significant advantage in disease-free survival (69% versus 57%, P < .0001; relative risk = 0.66; 95% CI = 0.58-0.74), distant disease-free survival (76% versus 67%, P < .0001; relative risk = 0.70; 95% CI = 0.61-0.81), and survival (80% versus 76%, P = .02; relative risk = 0.84; 95% CI = 0.71-0.99) was found for patients in the group first assigned to receive tamoxifen. The survival benefit extended to those 49 years of age or younger and to those 50 years of age or older. Tamoxifen therapy was associated with a 37% reduction in the incidence of contralateral (opposite) breast cancer (P = .007). Through 4 years after the reassignment of tamoxifen-treated patients to either continued-therapy or placebo groups, advantages in disease-free survival (92% versus 86%, P = .003) and distant disease-free survival (96% versus 90%, P = .01) were found for those who discontinued tamoxifen treatment. Survival was 96% for those who discontinued tamoxifen compared with 94% for those who continued tamoxifen treatment (P = .08). A higher incidence of thromboembolic events was seen in tamoxifen-treated patients (through 5 years, 1.7% versus 0.4%). Except for endometrial cancer, the incidence of second cancers was not increased with tamoxifen therapy. CONCLUSIONS AND IMPLICATIONS: The benefit from 5 years of tamoxifen therapy persists through 10 years of follow-up. No additional advantage is obtained from continuing tamoxifen therapy for more than 5 years.     

Pruritus as a presenting symptom of chronic hepatitis C

Pruritus is a common symptom in cholestatic liver disease but is rare in chronic hepatitis C. Eight patients with chronic hepatitis C and severe pruritus were compared with regard to biochemical, serological, and histological features to eight disease controls with primary biliary cirrhosis and seven with cirrhosis due to hepatitis C. Among those with severe pruritus associated with chronic hepatitis C, serum aminotransferases were raised in all, alkaline phosphatase in four, and gamma-glutamyl-transpeptidase levels in all except one. Serum cholylglycine levels were elevated in seven of eight patients. Liver biopsies showed moderate to severe fibrosis in all patients and cirrhosis in five. Compared to control subjects with cirrhosis due to hepatitis C but no pruritus, ductopenia, and cholestatic changes were prominent, although less so than in controls with primary biliary cirrhosis. Chronic hepatitis C with moderate to severe fibrosis may result in low-grade cholestasis with pruritus, possibly in association with bile duct disappearance.     

Circadian changes in levels of free amino acids in rat retina, and regulation of them by melatonin

Alpha-tocopherol (vitamin E) is an important fat-soluble antioxidant in biological systems and, as a result of scavenging reactive oxygen, it is converted to alpha-tocopherylquinone. Alpha-tocopherol binds to alpha-tocopherol transfer protein (alphaTTP) in the liver cytosol, whereas alpha-tocopherylquinone does not. We found that alpha-tocopherylquinone binds to a liver protein with a molecular mass of about 40 kDa that is distinct from alphaTTP. This alpha-tocopherylquinone binding protein was purified further by multiple-step column chromatography. Sodium dodecylsulfate-polyacrylamide gel electrophoresis of the final preparation yielded a single band with an apparent molecular mass of 25 kDa, which microsequencing revealed was identical to glutathione-S-transferase (GST). The GST activity was inhibited in the presence of alpha-tocopherylquinone, as it is by other non-substrate ligands for GST, confirming that GST and alpha-tocopherylquinone interact directly. Alpha-tocopherylquinone binds to GST and may be transported to the site of metabolism or excreted in the bile as other non-substrate ligands for GST.     

Comparative study of three antineoplastic alkylating agents on DNA

The influence of three alkylating anticancer preparations phosphamide, sarcolysine, cyclophosphane on content of the 5-methylcytosine and parameters of the melting DNA of the liver healthy animals and tumor sarcoma 45 was investigated. It was shown, that among the investigated preparations cyclophosphane has stronger anticancer influence and comparatively weaker side effect on DNA liver. We came to the conclusion that it is preferable to use this preparation.     

Biomechanics of atherosclerotic plaque

Atherosclerosis is the leading cause of death in the U.S. In balloon angioplasty, pressure is applied directly to atherosclerotic plaque to reopen the occluded blood vessel. The mechanical behavior of the plaque often determines the outcome of the angioplasty. Little information on the material properties of atherosclerotic plaque is available, yet the properties govern the plaque's behavior. Our discussion of the experimental testing and numerical analysis of plaque is directed toward summarizing the current knowledge of plaque material properties. Atherosclerotic plaque exhibits a wide range of behaviors consistent with the variability in the underlying composition. Overall, plaques exhibit nonlinear and inelastic mechanical behavior, although geometry and material properties are not well known. The histomorphological composition is critical in determining the plaque's mechanical response. Finite element approximations have been used to study the stresses developed in the diseased vessel; however, material properties are a critical component of a finite element analysis: the predictive capabilities depend on how accurately the material is modeled. When more information on plaque behavior is generated through careful and extensive experimental investigations, better models will be constructed to more accurately predict plaque responses. As the biomechanics community learns about plaque mechanics, we can use the knowledge to enhance the reliability of interventional procedures.     

Increased living donor volunteer rates with a formal recipient family education program

As part of our ongoing studies to characterize molecular alterations in a well-defined series of surgically resected esophageal cancers, we examined the expression of 2 ras-regulated genes, whose products (osteopontin and cathepsin L) previously were shown to be associated with tumor invasion and metastasis. RNA was extracted from primary esophageal tumors (adenocarcinomas, 19; squamous-cell carcinomas, 6) and matched histologically normal esophageal mucosa from the distant resection margin. Northern analysis was used to quantitate RNA, relative to an 18S rRNA control, and immunohistochemistry to assess the tissue distribution of osteopontin. In addition, H-, K- and N-ras mutations were studied in the same tissues using PCR and hybridization with allele (mutant)-specific oligonucleotide probes. We demonstrated a K-ras mutation (codon 12, GTT) in one esophageal adenocarcinoma. The ras-regulated gene osteopontin was over-expressed in 100% of squamous-cell carcinomas and in 58% of adenocarcinomas relative to matched normal esophageal mucosa. Patterns of immunoreactivity for osteopontin protein also varied between squamous-cell carcinomas (tumor cell staining) and adenocarcinomas (predominantly tumor-infiltrating macrophages). Expression of cathepsin L also varied with esophageal tumor histology, with over-expression in 58% of primary esophageal adenocarcinomas and 33% of squamous-cell cancers.