The 2'-substituted analog of poly(inosinic acid) ((I)n), poly(2'-fluoro-2'-deoxyinosinic acid) ((dIfl)n) served as an effective template for the RNA-directed DNA polymerase (reverse transcriptase) from Moloney murine leukemia virus. When assayed under the same conditions, the parent compound (I)n showed little, if any, template activity. In the presence of other templates, i.e. poly (2-O-methylcytidylic acid), (dIfl)n could also assume the role of primer for the reverse transcriptase reaction, whereas, again, (I)n failed to do so.

Dose-Response Relationship, Drug↗

PubMedDate not supplied

Biosynthesis of polyhydroxyalkanoates (PHA) by recombinant Ralstonia eutropha and effects of PHA synthase activity on in vivo PHA biosynthesis.

Recombinant strains of Ralstonia eutropha PHB 4, which harbored Aeromonas caviae polyhydroxyalkanoates (PHA) biosynthesis genes under the control of a promoter for R. eutropha phb operon, were examined for PHA production from various alkanoic acids. The recombinants produced poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) [P(3HB-co-3HHx)] from hexanoate and octanoate, and poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxypentano ate) [P(3HB-co-3HV-co-3HHp)] from pentanoate and nonanoate. One of the recombinant strains, R. eutropha PHB 4/pJRDBB39d3 harboring ORF1 and PHA synthase gene of A. caviae (phaC(Ac)) accumulated copolyesters with much more 3HHx or 3HHp fraction than the other recombinant strains. To investigate the relationship between PHA synthase activity and in vivo PHA biosynthesis in R. eutropha, the PHB- 4 strains harboring pJRDBB39d13 or pJRDEE32d13 were used, in which the heterologous expression of phaC(Ac) was controlled by promoters for R. eutropha phb operon and A. caviae pha operon, respectively. The PHA contents and PHA accumulation rates were similar between the two recombinant strains in spite of the quite different levels of PHA synthase activity, indicating that the polymerization step is not the rate-determining one in PHA biosynthesis by R. eutropha. The molecular weights of poly(3-hydroxybutyrate) produced by the recombinant strains were also independent of the levels of PHA synthase activity. It has been suggested that a chain-transfer agent is generated in R. eutopha cells to regulate the chain length of polymers.

Acyltransferases↗

PubMedDate not supplied

Improved production of poly(4-hydroxybutyrate) by Comamonas acidovorans and its freeze-fracture morphology.

Production of poly(4-hydroxybutyrate) [P(4HB)] by Comamonas acidovorans JCM10181 was studied by introducing additional copies of its PHA synthase gene and the beta-ketothiolase gene. A multi-copy-number broad-host-range plasmid vector, pJRD215, was modified to contain the strong hybrid trc promoter in order to express these genes in the wild-type C. acidovorans. Increased copy-number of genes resulted in significant increase in the activities of corresponding enzymes, which could further be increased by inducing with isopropyl-beta-D-thiogalactopyranoside (IPTG), indicating that the expression is under the transcriptional control of the trc promoter. P(4HB) biosynthesis in the recombinant C. acidovorans increased 2-fold to constitute more than 60 wt% of the dry cell weight. No significant decrease in the number-average molecular weights of P(4HB) in the recombinant strain was observed when compared with that of the wild-type. Freeze-fracture electron microscopy of intracellular P(4HB) granules revealed almost similar fracture morphology to the well-known mushroom-type deformation shown by polyhydroxyalkanoates with medium-chain-length monomers.

Acetyl-CoA C-Acyltransferase↗

PubMedDate not supplied

Influence of superstition on the date of hospital discharge and medical cost in Japan: retrospective and descriptive study.

OBJECTIVES: To determine the influence of superstition about Taian (a lucky day)-Butsumetsu (an unlucky day) on decision to leave hospital. To estimate the costs of the effect of this superstition. DESIGN: Retrospective and descriptive study. SETTING: University hospital in Kyoto, Japan. SUBJECTS: Patients who were discharged alive from Kyoto University Hospital from 1 April 1992 to 31 March 1995. MAIN OUTCOME MEASURES: Mean number, age, and hospital stay of patients discharged on each day of six day cycle. RESULTS: The mean number, age, and hospital stay of discharged patients were highest on Taian and lowest on Butsumetsu (25.8 v 19.3 patients/day, P=0.0001; 43.9 v 41.4 years, P=0.0001; and 43.1 v 33.3 days, P=0.0001 respectively). The effect of this difference on the hospital's costs was estimated to be 7.4 million yen (¿31 000). CONCLUSION: The superstition influenced the decision to leave hospital, contributing to higher medical care costs in Japan. Although hospital stays need to be kept as short as possible to minimise costs, doctors should not ignore the possible psychological effects on patients' health caused by dismissing the superstition.

Adult↗

PubMedDate not supplied

Reanalysis of unruptured intracranial aneurysm management: effect of a new international study on the threshold probabilities.

OBJECTIVE: This report updates previous clinical decision analysis for patients with unruptured intracranial aneurysm (UN-AN) based on newly published data and discusses the role of reanalysis in individual decision making. METHODS: The authors employed probabilities for the natural history of UN-AN and results of preventive surgery based on the report by the International Study of Unruptured Intracranial Aneurysms. Probabilistic sensitivity analysis with Monte Carlo simulation and traditional n-way sensitivity analyses were used to assess the uncertainty of clinical decisions. RESULTS: The baseline decision in favor of preventive surgery is reversed by new data from the international study. Probabilistic sensitivity analyses revealed several populations showing heterogeneity in terms of strategy selection. One- and two-way sensitivity analyses detected two important factors for decision making: annual rupture rate and utility for knowingly living with UN-AN. CONCLUSIONS: Annual UN-AN rupture rate and the utility for knowingly living with UN-AN are key factors when deciding on a therapeutic strategy. Also, updating published decision analyses can improve clinical decision making by integrating clinical judgment and newly available clinical data.

Adult↗

PubMedDate not supplied

Cost-effectiveness of screening strategies for left main coronary artery disease in patients with stable angina.

To define optimal strategies for screening for left main coronary artery disease (LMCAD), the authors evaluated the cost-effectiveness of exercise tolerance testing and cardiac catheterization in patients with mild stable chest pain, such as patients with definite or probable angina in the Coronary Artery Surgery Study registry (prevalence of LMCAD = 9%). Performance characteristics of the exercise test, operative mortality, long-term survival rates, and rates of crossing over to surgical therapy for patients initially managed with medical therapy were derived from pooled literature data; cost estimates were based on local charge data. Strategies using the exercise test to identify candidates for catheterization were associated with longer life expectancies than either the conservative strategy in which patients would be observed or the more aggressive strategy in which all patients would undergo coronary angiography. The most cost-effective option was to screen patients with an exercise test and to perform catheterization in patients with greater than or equal to 2 mm of ST-segment change. Compared with a strategy of catheterization for greater than or equal to 3 mm of ST-segment change only, this strategy increased life expectancy at marginal costs per year of life saved ranging from $11,263 to $18,100 for 40- to 70-year-old patients, respectively, while, compared with a strategy of observation unless symptoms worsened, its incremental cost-effectiveness was $6,510 to $12,428 per year of life saved. Thus, screening patients with stable chest pain syndromes with exercise tests and performing catheterization for patients with greater than or equal to 2 mm of ST-segment change has cost-effectiveness comparable to that of the treatment of moderate diastolic hypertension.

Adult↗

PubMedDate not supplied

Management of unruptured intracranial aneurysm in Japan: a Markovian decision analysis with utility measurements based on the Glasgow Outcome Scale.

The purpose of this study was to analyze the management of individual patients with unruptured intracranial aneurysms (UN-ANs) using a decision-analytic approach. Transition probabilities among Glasgow Outcome Scale (GOS) categories were estimated from the published literature and data from patients who had been treated at Kitasato University Hospital. Utilities were obtained from 140 health providers based principally on the GOS. Baseline analysis for a healthy 40-year-old man with an anterior UN-AN less than 10 mm in diameter showed that the quality-adjusted life expectancies for preventive operation and follow-up were 15.34 and 14.66 years, respectively. For a follow-up strategy to be preferred, the annual rupture rate had to be as low as 0.9%. These results were sustained through extensive sensitivity analysis. The results support preventive operation for UN-ANs, and identify problems that can be clarified with a well-designed stratified clinical trial.

Adult↗

PubMedDate not supplied

Nephrotic syndrome associated with generalized amyloidosis and IgM-monoclonal proteinemia.

A 67-year-old woman was admitted for nephrotic syndrome. In spite of the lack of lymphadenopathy, hepatosplenomegaly and serum hyperviscosity, remarkable monoclonal IgM-proteinemia was demonstrated. Amyloid kidney was shown by renal biopsy. However, in the bone marrow and other organs, neither proliferation nor invasion of monoclonal immunoglobulin-producing cells was revealed by immunohistological investigations of the specimens biopsied or examined at autopsy, excluding Waldenström's macroglobulinemia. Immunosuppressive chemotherapy with cyclophosphamide, vincristine and prednisolone was effective in reducing serum IgM, but could not slow the progression of renal failure. This case suggested the association of generalized amyloidosis with excessive IgM-proteinemia caused by a non-malignant mechanism.

Aged↗