An activator of blood coagulation factor X from the venom of Bungarus fasciatus

A specific activator of blood coagulation factor X was purified from the venom of Bungarus fasciatus by gel filtration and by ion-exchange chromatography on a Mono-Q column (FPLC). It consisted of a single polypeptide chain, with a mol. wt of 70,000 in reducing and non-reducing conditions. The enzyme had an amidolytic activity towards the chromogenic substrates S-2266 and S-2302 but it did not hydrolyse S-2238, S2251 or S-2222, which are specific substrates for thrombin, plasmin and factor Xa, respectively. The enzyme activated factor X in vitro and the effect was Ca2+ dependent with a Hill coefficient of 7.9. As with physiological activators, the venom activator cleaves the heavy chain of factor X, producing the activated factor Xa alpha. The purified factor X activator from B. fasciatus venom did not activate prothrombin, nor did it cleave or clot purified fibrinogen. The amidolytic activity and the factor X activation activity of the factor X activator from B. fasciatus venom were readily inhibited by serine protease inhibitors such as diisopropyl fluorophosphate (DFP), phenylmethanesulfonyl fluoride (PMSF), benzamidine and by soybean trypsin inhibitor but not by EDTA. These observations suggest that the factor X activator from B. fasciatus venom is a serine protease. It therefore differs from those of activators obtained from Vipera russelli and Bothrops atrox venoms, which are metalloproteinases.     

Phase relation, crystal structure, and magnetic properties of La-Co-Si alloys

OBJECTIVES: To identify ICU-specific predictors of mortality. DESIGN: An inception cohort study. SETTING: Barnes Hospital, an academic tertiary care center. PATIENTS: Consecutive patients, requiring mechanical ventilation, admitted to the medical intensive care unit (ICU) (75 patients), surgical ICU (100 patients), and cardiothoracic ICU (102 patients). INTERVENTIONS: Prospective data collection and outcomes evaluation. MEASUREMENTS AND MAIN RESULTS: Stepwise logistic regression analysis identified the following variables to be independent predictors of mortality for the individual ICUs: medical ICU, an Organ System Failure Index (OSFi) greater than or equal to 3; surgical ICU, OSFI greater than or equal to 3; cardiothoracic ICU, OSFI greater than or equal to 3, requiring acute dialysis, and the occurrence of an iatrogenic event. The same analysis was repeated after removing the OSFI as a potential confounding variable. Independent predictors of mortality identified in this subsequent analysis were as follows: medical ICU, occurrence of renal failure; surgical ICU, supine head positioning, acute physiology score greater than or equal to 10, preadmission lifestyle score greater than or equal to 2; cardiothoracic ICU, requiring acute dialysis, occurrence of ventilator-associated pneumonia, and the occurrence of an iatrogenic event. CONCLUSIONS: We identified the presence of ICU-specific predictors of mortality amongst the three ICUs examined. These data suggest that ICU-specific interventions could be developed to improve the quality of patient care and potentially to reduce patient mortality.     

The anatomic basis and clinical applications of flaps based on the posterior tibial vessels

The vascular anatomy of the posterior tibial vessels has been studied in 20 legs of 10 cadavers. The number, size and distribution of the direct cutaneous and direct muscle branches of the posterior tibial vessels were recorded. For analysis, the leg was divided into four equal segments, Zone I being the most distal and Zone IV the most proximal. The direct cutaneous branches were found to cluster mainly around Zone II. The direct muscle branches to the soleus and flexor digitorum longus muscles arose chiefly in Zones II and III. Based on this knowledge, we performed fasciocutaneous, island soleus muscle, musculo-fasciocutaneous and flexor digitorum longus muscle flaps based on the posterior tibial vessels in 12 patients. Four were free fasciocutaneous flaps and eight were pedicled flaps. All flaps survived and there were no major complications. Delayed wound healing was encountered in three patients.     

An isometric predictor for maximum acceptable weight of lift for Chinese men

The aim of this study was to examine the practicality of the modified isometric strength tests to predict the maximum acceptable weight of lift (MAWL) of Chinese men. The modified strength tests allow the participant to pull on the load cell in front of the body and to apply force in a functional free posture. Both the modified and the standard strength data of each participant were used as predictors for the MAWLs. The prediction models were constructed and evaluated under task conditions of two lifting ranges, two box sizes, and three lifting frequencies. To realize the effect of modifications, testing posture was recorded and the joint angles were calculated. A stepwise multiple regression analysis indicated that modified composite strength (MCS), chest circumference, and acromial height accounted for 86% to 91% of the variance. Because the strength of the upper extremity body was also recruited in the test, the weak upper extremity strength of the Chinese participants would therefore be better reflected. Evidence for the existence of a close match between MAWL and MCS values, as well as the task conditions for its existence, suggest that a simple isometric strength measure is a good predictor for the MAWL.     

Increased risk of malignancy in patients with systemic lupus erythematosus

BACKGROUND: Systemic lupus erythematosus is a chronic, multisystem, autoimmune disorder that primarily affects women. Morbidity and mortality have improved for lupus patients during the last 15 years. An increased risk of malignancy in patients with lupus has been shown in some, but not all studies. The purpose of this study was to ascertain cancer risk in lupus patients by linking two disease registries. METHODS: Participants in the Chicago Lupus Cohort included 616 women with lupus who were residents of Cook County, Illinois. They were seen during 1985-1995 at 4 University, inner city, and suburban inpatient and outpatient clinics in Chicago. Malignancies occurring in these subjects during the study interval, 1985-1995, were identified from the Illinois State Cancer Registry by matching name, birthdate, and social security number. Standardized incidence ratios (SIRs) were estimated for all malignancies in this cohort of lupus patients using age, gender, and all race or race-stratified specific cancer incidence data from Cook County, Illinois. RESULTS: The registry linkage study with the Illinois State Cancer Registry documented that 30 women with lupus had a malignancy. The expected number of malignancies for women in the lupus cohort was 15.0. There were 8 cases of breast cancer and 4 each of lung and cervical cancer. In the remaining 14 women, 12 different types of cancers were noted. The SIR and 95% confidence interval (CI) for malignancy for all women with lupus in the study were 2.0 (1.4, 2.9) and lung cancer was the only individual cancer increased in all women--SIR and 95% CI were 3.1 (1.3, 7.9). In the analysis stratified by race, the risk of malignancy (SIR and 95% CI) was increased in Caucasian women, 2.3 (1.4, 3.9). Breast cancer was the only individual cancer increased in Caucasian women with lupus with an SIR and 95% CI of 2.9 (1.4, 6.4). CONCLUSIONS: Lupus patients have an increased risk of malignancy. Breast, lung, and gynecological malignancies were the most common malignancies observed in the cohort and breast cancer was significantly increased in Caucasian women.     

Adenoviral-mediated suicide gene therapy for hepatic metastases of breast cancer

Metastases of breast cancer are a major cause of treatment failure. To evaluate the therapeutic efficacy of suicide gene therapy in metastatic breast cancer, we used the herpes simplex virus thymidine kinase (HSV-tk) gene followed by ganciclovir (GCV) administration to treat breast cancer, generated by an adenocarcinoma cell line MOD in syngeneic mice. The bystander effect of HSV-tk + GCV on tumor cell killing was illustrated by demonstrating complete regression of subcutaneous tumors consisting of 90% parental tumor cells and 10% HSV-tk transformed tumor cells. To establish a model of breast cancer metastases in the liver, tumors were generated by intra-hepatic implantation of MOD cells in syngeneic animals. Two weeks after tumor cell implantation, replication defective adenoviral vectors expressing HSV-tk (ADV.tk), or beta-galactosidease (ADV. beta-Gal) were injected intratumorally, followed by buffer or GCV administration. Treatment with ADV.tk + GCV resulted in significant regression of tumor (P < .001), as assessed by computerized morphometric analysis of residual tumor. This was reflected as a significant prolongation of survival in treated animals (P < .001). These results demonstrate that ADV-mediated suicide gene therapy in vivo can be incorporated in a comprehensive treatment strategy for liver metastases of breast cancer.     

Electron microscopic study of the permeability of terminal blood vessels of the M. triceps brachii to horseradish peroxidase in fetal, juvenile and adult rats

At the basis of some ultrastructural differences in fetal, juvenile and adult rat triceps muscle capillaries as described in preliminary papers the permeability of these capillaries to horse radish peroxidase was investigated. Capillaries of fetal and juvenile rats up to the 3rd week after birth were impermeable to horse radish peroxidase (HRP) for 2 and 10 minutes after injection, which can be explained with the low pinocytotic activity and the more complex structure of the junctions. Capillaries of the triceps brachii muscle in adult rats aged 2 month and more show a low permeability to HRP 2 and 5 minutes and a high permeability 15 minutes after the injection of the tracer. In the capillary segment of the terminal bed the tracer was traversed especially by the means of vesicles and some transendothelial channels built by linked vesicles. The interendothelial junctions seemed to be tight. In the venular segment of th capillaries and in small postcapillary venules additional to the vesicular transport a high permeability of some junctions was stated. The significance of the different permeability of distinct segments of the terminal vascular bed to small macromolecules is discussed with respect to the theories of th physiologists and compared with the results of recent investigators.     

Systemic meningococcal infections in patients with acquired complement deficiency

Congenital deficiency of the late components of the complement may predispose the individual to systemic meningococcal infection. Assuming that patients with acquired complement deficiencies may also have an increased risk of contracting meningococcal infections, a retrospective and prospective study to assess this association was conducted. Over 20 years (1970-1989), 30 patients with meningococcemia or meningococcal meningitis, proven by blood or CSF culture, were treated at the Beilinson Medical Center. Only one patient died of the infection. Risk factors were found in three patients (10%). One had a congenital deficiency of C7, and two had acquired complement deficiency due to systemic lupus erythematosus (SLE) and membranoproliferative glomerulonephritis (MPGN). These latter two patients had low serum concentration of C3 and C4 and reduced complement hemolytic activity before onset of the infection. Since the incidence of culture-proven systemic meningococcal infection in the Jewish population in central Israel is 1/100,000, and the prevalence of SLE and MPGN is, at most, 250/100,000, the finding of two patients with meningococcal infection and these rare disorders is over 100 times the expected incidence. We conclude that patients with acquired complement deficiency are at significant risk of meningococcal infection.