Induced candidosis in mice with artificially established oral flora

The aim of this study was to gauge the effect of an artificially established flora, unnatural for mice, on the induction of oral candidosis in mice. Four groups of BALB/c mice were compared; conventional Candida albicans-free mice, "germ-free" mice which had been inoculated with Candida-free human saliva, germ-free mice which had been exposed to a cocktail of Streptococcus mitis, S. sobrinus and S. sanguis, and uncontaminated germ-free mice. After exposure to C. albicans via drinking water, the four groups of mice were killed and their oral cavities examined for candidal growth and oral lesions. Conventional mice yielded significantly less candidal growth and exhibited significantly fewer oral lesions than the other three groups. Candidal lesions in the two groups of contaminated germ-free mice were significantly fewer than in the uncontaminated germ-free mice. The latter exhibited extensive candidal lesions with little inflammatory infiltrate. It is concluded that mice with human oral micro-organisms have some resistance against candidal infection albeit at a reduced level, that mice with natural oral flora are highly resistant, and that germ-free mice are extremely susceptible to C. albicans infection.     

Mitosene-DNA adducts. Characterization of two major DNA monoadducts formed by 1,10-bis(acetoxy)-7-methoxymitosene upon reductive activation

Reductive activation of racemic 1,10-bis(acetoxy)-7-methoxymitosene WV15 in the presence of DNA, followed by enzymatic digestion and HPLC analysis, revealed the formation of various DNA adducts. Reduction is a necessary event for adduct formation to occur. This reductive activation was performed under hypoxic conditions in various ways: (1) chemically, using a 2-fold excess of sodium dithionite (Na2S2O4), (2) enzymatically using NADH-cytochrome c reductase, (3) electrochemically on a mercury pool working electrode, and (4) catalytically, using a H2/PtO2 system. Five different mitosene-DNA adducts were detected. These adducts were also present when poly(dG-dC) was used instead of DNA, but were absent with poly(dA-dT). All were shown to be adducts of guanine. Reduction of 1, 10-dihydroxymitosene WV14 in the presence of DNA did not result in detectable adduct formation, demonstrating the importance of good leaving groups for efficient adduct formation by these mitosenes. Finally, two of the adducts were isolated and their structures elucidated, using mass spectrometry, 1H NMR and circular dichroism (CD). The structures were assigned as the diastereoisomers N2-(1"-n-hydroxymitosen-10"-yl), 2'-deoxyguanosine (n = alpha or beta). These type of adducts, in which the mitosene C-10 is covalently bonded to the N-2 of a guanosylic group, are different from the well-known mitomycin C 2'-deoxyguanosine monoadducts, that is linked via the mitomycin C C-1 position, demonstrating that the order of reactivity of the C-1 and C-10 in these mitosenes is reversed, as compared to mitomycin C. The 7-methoxy substituent of WV15 is a likely factor causing this switch. Evidence is presented that the 7-substituent of mitosenes also influences their DNA alkylation site. Adducts 4 and 5 represent the first isolated and structurally characterized covalent adducts of DNA and a synthetic mitosene.     

The dynamics of prostate specific antigen in hormone refractory prostate carcinoma: an analysis of cancer and leukemia group B study 9181 of megestrol acetate

BACKGROUND: Although many physicians measure serum prostate specific antigen (PSA) during the follow-up of patients with hormone refractory prostate carcinoma (HRPC), little has been done to formalize the determination of how these serial values of PSA impact on prognosis. To understand HRPC fully, make decisions about choices of treatment as well as about clinical research on treatments for HRPC patients, and design appropriate measures of PSA response, it seems that first it would be necessary to understand how these serial measures of PSA relate to survival. The purpose of this study was to determine how repeated measurements of PSA impact on the probability of imminent death for patients with HRPC. METHODS: One hundred forty-eight men with HRPC were enrolled in Cancer and Leukemia Group B Study 9181, in which they were treated with either a low dose (160 mg/day) or a high dose (640 mg/day) of megestrol acetate (MA). Because preliminary data analysis indicated that these treatments had no effect on survival, the authors pooled the data to analyze the overall dynamics of PSA and survival during the follow-up period. The authors attempted to correlate initial and monthly PSA measurements, which were mandated by the study protocol, with the probability of death at any time during follow-up. For statistical analysis, the Cox proportional hazards model and the general linear model were used. In addition to the level of PSA, the authors used the relative velocity of PSA, which was defined as (dy/dt)/y, with "y" symbolizing serum PSA and "t" symbolizing time. RESULTS: Both log(PSA) and the average relative velocity of PSA (rva) were significantly correlated with survival time (P=0.0001 and P=0.0008, respectively), and the analysis performed with the Cox proportional hazards model yielded the following formula for a PSA hazard score: PSA hazard score =0.251*(log(PSA) - mean log(PSA)) + 24.5*(rva - mean rva) This hazard score tended to be higher for patients who were about to die. For example, there was a close correlation between the hazard score and the probability of death as the next observed event. Furthermore, the hazard score provided a dynamic measure of how PSA was affected by treatment. CONCLUSIONS: The average relative velocity of PSA has been identified by the authors as a new measure of the dynamics of PSA in HRPC. It can be determined from sequential values of PSA. This average, together with the log(PSA), are significantly related to the probability of imminent death.     

Hypermobility syndrome. When too much activity causes pain

Hypermobility of joints and spine is a consequence of abnormal laxity of ligaments, joint capsules and intervertebral discs. Hypermobility per se is a state, not a disease. However, it may lead to generalized arthralgia or localized symptoms (frequent ankle sprains, knee effusions, dislocations of the shoulders of recurrent episodes of back pain). These events may occur even after minor strains. Young women are preferentially affected. The term "hypermobility syndrome" is defined as a combination of hypermobility with arthralgia, low back pain, frequent dislocation or sprains. It is often the result of a hereditary disorder of connective tissue. Individuals with hypermobility are at increased risk for premature osteoarthrosis or polytopic disc degeneration of the spine. However, the vast majority of hyperlax individuals are free of symptoms. Those with symptoms who do not develop osteoarthrosis or disc degeneration usually experience spontaneous improvement with increasing age, thus losing their juvenile hyperlaxity. This usually occurs between the ages of thirty and forty. The present review article also provides guidelines for management and patient information.     

Blue LED growth from 2 inch to 8 inch

Growth of blue InGaN based LED structures on sapphire wafers from 2 inch to 8 inch in diameter was investigated using the Veeco K465 MOCVD platform. Our results indicate that the same pressure,rotation rate and hydride flows can be used for all wafer sizes. AFM and X-ray studies reveal that all wafer sizes have comparable high-quality crystallinity and defect levels for GaN and InGaN/GaN MQW growth. Although the larger diameter wafers exhibit larger wafer bow due to lattice and thermal mismatch,with proper ...     

Performance of GEM2 on the ELLPACK problem population

The Pilot global element program GEM2 MK1.0 has been used to solve the two-dimensional problems in the ELLPACK population of partial differential equation test problems. The performance achieved is summarized in this paper; special attention is paid to those problems which are singular or near singular, and for which comparisons have been published by Houstis and Rice.¹²