Ubiquitin and apoptosis in the corpus luteum of the marmoset monkey (Callithrix jacchus)

The thiazolidinedione analogue troglitazone is an antidiabetic agent that improves insulin resistance in rodents and humans. Although coronary artery disease is common in patients with the insulin resistance syndrome, the effects of troglitazone on smooth muscle cells (SMC) have not been fully elucidated. We therefore examined the effects of troglitazone on cell growth and glucose uptake in human aortic SMC. Mitogen-activated protein (MAP) kinase activity and glucose transporter (Glut) 1 mRNA levels were also studied. In the absence of troglitazone, insulin (10(-7) M) caused a 2-fold increase of DNA synthesis in SMC and troglitazone suppressed the increase of DNA synthesis in a dose-dependent manner. This growth suppression was accompanied by inhibition of MAP kinase activity. On the other hand, troglitazone significantly increased Glut 1 mRNA and enhanced glucose uptake in SMC. These results suggest that troglitazone affects the insulin signaling pathways in SMC and suppresses growth while promoting glucose uptake. Our findings support the application of troglitazone as an inhibitor of SMC proliferation in patients with insulin resistance.     

Age-related changes in gastric mucosal repair and proliferative activities in rats exposed acutely to aspirin

OBJECTIVES: (1) To determine whether and how outcome measurements in the ECASS trial are influenced by a shorter time window (0-3 vs. 3-6 h) between onset of symptoms and start of thrombolytic therapy using recombinant tissue plasminogen activator (rt-PA) in acute ischemic stroke. (2) To discuss the results of the ECASS 0- to 3-hour cohort with the results of the National Institute of Neurological Disorders and Stroke Study (NINDSS). DESIGN AND ANALYSIS: Analysis of the 0- to 3-hour and the 3- to 6-hour cohort in accordance with the ECASS protocol. Comparative analysis of the ECASS and NINDSS results following the NINDSS protocol using dichotomized endpoints. MAIN OUTCOME MEASURES: Primary endpoints: modified Rankin Scale, Barthel Index; secondary endpoints: combined Barthel/Rankin, long-term Scandinavian Stroke Scale, National Institutes of Health Stroke Scale, mortality at 30 and 90 days, occurrence of intracranial hemorrhage. NINDS trial endpoint: favorable outcome as defined in the NINDS trial. RESULTS: In ECASS, 87 patients were randomized within 3 h of stroke onset. Differences in favor of rt-PA treatment can be found for all primary and secondary outcome measures in the ECASS 0- to 3-hour cohort, except for mortality at day 30, which is somewhat higher in the rt-pA-treated group. However, due to the small sample size, the differences do not reach statistical significance. Early infarct signs (as defined by the ECASS protocol) are found as early as 2 h after stroke onset. Parenchymal hemorrhages are found significantly more often among rt-PA-treated patients. The results in the ECASS 0- to 3-hour cohort fit well with the results in NINDSS. CONCLUSION: Data from the 3-hour ECASS cohort support the efficacy of early thrombolytic therapy in acute hemispheric stroke patients. Comparing bleeding complications between the ECASS and NINDSS is difficult because of differences in the definition and occurrence of hemorrhagic events.     

Pneumococcal polysaccharide vaccine in children with chronic renal disease: a prospective study of antibody response and duration

We studied the antibody response to pneumococcal serotypes 3 and 14 after pneumococcal polysaccharide vaccine was administered to 41 children with renal disease. One month after vaccination, 76% and 61% of patients achieved at least a twofold titer rise to serotypes 3 and 14, respectively; this finding was comparable to historic control values. One year after vaccination, the majority of patients retained protective antibody levels. Achieving a titer > or = 1.0 microgram/ml IgG at 1 month was highly predictive of retaining a protective antibody level > or = 0.15 microgram/ml at 1 year.     

Determinants of CPT-11 and SN-38 activities in human lung cancer cells

Irinotecan (CPT-11) is a semisynthetic camptothecin derivative with a broad spectrum of anti-tumour activity. Carboxylesterase (CE) catalyses the conversion of CPT-11 to SN-38 (7-ethyl-10-hydroxycamptothecin), the active form of CPT-11. The antiproliferative effects of CPT-11 and SN-38, CE-activity and topoisomerase I protein expression were investigated in five human small-cell lung cancer (SCLC) cell lines and four human non-small-cell lung cancer (NSCLC) cell lines. Antiproliferative activity, expressed as IC50 values, was determined using the MTT assay. CPT-11 was significantly more active in SCLC than in NSCLC cell lines (P = 0.0036), whereas no significant difference between histological types was observed with SN-38. A significant correlation (r2 = 0.52, P = 0.028) was observed between CE activity and chemosensitivity to CPT-11 but not to SN-38, and significantly higher CE activity was observed in SCLC compared with NSCLC cell lines (P = 0.025). Western blotting experiments showed topoisomerase I protein expressions within a factor of 2, and a granular nuclear staining was detectable in all cell lines by immunocytochemistry of cytospins. No correlation was observed between protein expression and sensitivity to CPT-11 or SN-38. Cellular and medium concentrations of CPT-11 and SN-38 were measured by high-performance liquid chromatography (HPLC) in one SCLC cell line with high CE activity and high sensitivity to CPT-11, and one NSCLC cell line with low sensitivity to CPT-11 and CE activity. Intracellular concentrations of CPT-11 and SN-38 were higher in the SCLC cell line, and this was associated with an increase in cellular uptake of CPT-11 compared with the medium, and an increased intracellular formation of SN-38. In conclusion, CE activity appears to be associated with higher sensitivity to CPT-11 in human lung cancer cell lines and may partly explain the difference in the in vitro sensitivity to CPT-11 between SCLC and NSCLC cells. The assessment of CE activity in clinical material of lung cancer patients undergoing treatment with CPT-11 may be warranted. However, other mechanisms may influence sensitivity to CPT-11, possibly including drug transport.     

Placing a bone graft more posteriorly may reduce the risk of pedicle screw breakage: analysis of an unexpected case of pedicle screw breakage

Studies on collagen in heart are important to understand the pathogenesis of myocardial necrosis and to evaluate cardiac function in infarcted heart. The present study has been undertaken to find out the alterations in collagen types in heart as well as serum proteins during myocardial injury in rats. A decreased collagen content was observed on day one which may be due to increased secretion of collagenase and proteases from inflammatory cells or from the myocardium. The changes noticed in the collagen types (I, III and V) indicated the altered elasticity of the heart. Histological studies were observed to correlate well with the biochemical changes in collagen. Evaluation of myocardial collagen could provide new approaches to the treatment of infarct size reduction.     

Role of Epstein-Barr virus in fine-needle aspirates of metastatic neck nodes in the diagnosis of nasopharyngeal carcinoma

The crystal structure of the peptide Boc-Phe-Val-OMe determined by X-ray diffraction methods is reported in this paper. The crystals grown from aqueous methanol are orthorhombic, space group P2(1)2(1)2(1),a = 11.843(2), b = 21.493(4), c = 26.676(4) A3 and V = 6790 A3. Data were collected on a CAD4 diffractometer using MoK alpha radiation (lambda = 0.7107 A) up to Bragg angle theta = 26 degrees. The structure was solved by direct methods and refined by a least-squares procedure to an R value of 6.8% for 3288 observed reflections. There are three crystal-lographically independent peptide molecules in the asymmetric unit. All the three molecules exhibit extended conformation. The sidechain of the Val2 residue shows two different conformations. The conformation of the peptide Boc-Phe-Val-OMe is compared with the conformation of Ac-delta Phe-Val-OH. It is observed that while Boc-Phe-Val-OMe exhibits an extended conformation, Ac-delta Phe-Val-OH shows a folded conformation. The results of this comparison highlight the conformation constraining property of the delta Phe residue. Interestingly, even though Boc-Phe-Val-OMe and Ac-delta Phe-Val-OH are conformationally different, they exhibit similar packing patterns in the solid state.     

Infection and stage conversion during murine pulmonary toxoplasmosis: a study with three different strains of Toxoplasma gondii

OBJECTIVE: To investigate whether intravenously administered liposomal alpha-tocopherol can protect the lung from the injurious action of Escherichia coli lipopolysaccharide (LPS). DESIGN: Prospective, randomized animal study. SETTING: Government research laboratory. SUBJECTS: Twenty adult male Sprague-Dawley rats. INTERVENTIONS: Animals were intravenously pretreated with alpha-tocopherol liposomes (20 mg alpha-tocopherol/kg body weight), plain liposomes, or saline. Twenty-four hours later, pretreated animals were challenged with an intravenous injection of LPS (E. coli 0111:B4, 1 mg/kg body weight), and killed 2 hrs after LPS challenge. MEASUREMENTS AND MAIN RESULTS: Challenge of saline-pretreated animals with LPS resulted in lung injuries as evidenced by an increase in wet lung weight and a reduction in pulmonary angiotensin converting enzyme (25%) and alkaline phosphatase (28%), injury markers of lung endothelial and epithelial type II cells, respectively. Also, LPS administration resulted in an increase in pulmonary myeloperoxidase and protease activities, indicative of a neutrophilic inflammatory response. Pretreatment of animals with liposomal alpha-tocopherol significantly attenuated the LPS-induced edematous lung weight response, and reduced the extent of injuries to the pulmonary endothelial and epithelial cells, demonstrated by a significantly smaller reduction in the corresponding enzyme marker activities. CONCLUSION: These results suggest that augmentation of the pulmonary antioxidant status can ameliorate LPS-induced lung injuries mediated by oxidative stress mechanisms.