Lethal and severe coronary arteritis in DBA/2 mice induced by fungal pathogen, CAWS, Candida albicans water-soluble fraction

CAWS is a microbial pathogen-associated molecular patterns (PAMPs) produced by Candida albicans. CAWS is a mannoprotein-beta-glucan complex and secreted into the culture supernatant. CAWS has various biological effects, causing acute shock and disrupting vascular permeability. Intraperitoneal administration of CAWS induces coronary arteritis in various strains of inbred mice. The CAWS-induced coronary arteritis is strain-dependent and most severe in DBA/2 mice with a significant number of these animals expiring with cardiomegaly during the observation period. In vivo and in vitro, splenocytes of DBA/2 mice produced various cytokines, such as IL-6, TNF-alpha, and IFN-gamma in response to CAWS. GM-CSF was also produced in response to CAWS. The production of cytokines was significantly enhanced in the presence of recombinant GM-CSF. In contrast, anti-GM-CSF significantly reduced the production of TNF-alpha and IFN-gamma. Augmented production of cytokines in response to CAWS would be a key to the severity of coronary arteritis.     

Molecular epidemiology of tuberculosis by the use of IS6110 restriction fragment length polymorphism: a study from 2001 to 2003

OBJECTIVE: To analyze the situation of tuberculosis infection by DNA fingerprinting in the middle and eastern part of Osaka, Japan. DESIGN: We performed IS6110 restriction fragment length polymorphism (RFLP) on 1200 isolates from tuberculosis patients who visited our hospital from January 2001 to December 2003. A cluster was defined as a series of isolates with more than 90% similarity by IS6110 RFLP and those with the same drug-susceptibility pattern. The isolates with fewer than six copies of IS6110 were considered to be clustered if the IS6110 RFLP patterns and the variable numbers of tandem repeats with 16 regions of ETR and MIRU "allele profile" were identical. RESULTS: The number of samples in incremental study periods was 422 in 2001, 817 between 2001 and 2002 and 1200 between 2001 and 2003. The percentage of clustered cases was 27.8% in 2001, 19.1% in 2002 and 19.5% in 2003. The cumulative percentage of clustered cases was 27.8% in the first year, 29.7% over two years and 32.6% over three years. The percentage of clustered cases of isolates with a drug resistance was significantly lower (25.0%) than that of drug susceptible isolates (33.7%). Next, we investigated the clustered cases by gender and age. The percentage of clustered cases with isolates from young males and females (0-19 years old) was 23.8%. In contrast, the percentage of clustered cases with isolates from 20-59 year-old females gradually decreased from 14.7% to 4.4%. Conversely, the percentage of clustered cases from young and middle aged male (20-59 years old) was higher (20.2%-32.4%) than that of females. CONCLUSION: The sharp increase in the cumulative cluster formation rate was curbed by the decline in the tuberculosis incidence rate in Osaka, Japan, after the first year of examination. We thought that this phenomenon suggests the success of the anti-tuberculosis measure in Japan.     

Good death in Japanese cancer care: a qualitative study

One of the most important goals of palliative care is achieving a "good death" or a "good dying process." The primary aim of this study was to identify the components of a Japanese "good death" through qualitative interviews with cancer patients, their families, physicians, and nurses. Semistructured interviews were conducted. Thirteen advanced cancer patients, 10 family members of such patients, 20 physicians, and 20 nurses were recruited from five regional cancer institutions in Japan. Content analysis was applied to answers, and 58 attributes were extracted and classified into 17 categories as follows: Freedom from pain or physical/psychological symptoms, Having a good family relationship, Dying in one's favorite place/environment, Having a good relationship with medical staff, Not being a burden to others, Maintaining dignity, Completion of life, Maintaining a sense of control, Fighting against cancer, Maintaining hope, Not prolonging life, Contributing to others, Control of future, Not being aware of death, Appreciating others, Maintaining pride, and Having faith. The most frequently cited category was "Freedom from pain or physical/psychological symptoms" and the least common was "Having faith." This study identified important components of a good death in Japan. A future quantitative survey is planned to clarify the generalizability of these findings as the primary endpoint of palliative care in Japan.     

A new system for the analysis of thermal judgments: multipoint measurements of skin temperatures and temperature-related sensations and their joint visualization

We report a new system for monitoring sensations of many body parts as well as comprehensively showing the distribution of overall skin temperature (T(sk)) and temperature-related sensations. The system consists of a console with 52 levers to report temperature-related sensations and software that facilitates the visualization of the distribution of T(sk) and temperature-related sensations by displaying them on a model of the human body. The system's utility was demonstrated with a physiological experiment involving three males and three females. They were exposed to step changes of ambient temperature from 23 degrees C to 33 degrees C. We measured T(sk) at 50 points, and the subjects concurrently provided estimates of local temperature sensation and thermal comfort/discomfort at 25 loci. This system greatly facilitates the perception and analysis of spatial relationships and differences in temperature and sensation in various areas of the body.     

Screening for vaginal shedding of cytomegalovirus in healthy pregnant women using real-time PCR: correlation of CMV in the vagina and adverse outcome of pregnancy

The impact of cytomegalovirus (CMV) infection of the genital tract during pregnancy on adverse pregnancy outcomes is not understood fully. A real-time PCR assay was used to determine vaginal shedding of CMV in 993 healthy pregnant Japanese women and the results were compared with the outcome of pregnancy. CMV DNA was detected in 76 (7.7%) of the women. The outcome of pregnancy could be determined finally in 848 women, of whom 60 (7.1%) were CMV positive. The carriers of CMV had an increased miscarriage rate (RR 6.96, 95% CI 2.04-23.84, P < 0.01). These findings suggest that latent genital tract CMV infection predisposes to adverse pregnancy outcomes.     

Crystal structures of gamma-glutamyltranspeptidase from Escherichia coli, a key enzyme in glutathione metabolism, and its reaction intermediate

Gamma-glutamyltranspeptidase (GGT) is a heterodimic enzyme that is generated from the precursor protein through posttranslational processing and catalyzes the hydrolysis of gamma-glutamyl bonds in gamma-glutamyl compounds such as glutathione and/or the transfer of the gamma-glutamyl group to other amino acids and peptides. We have determined the crystal structure of GGT from Escherichia coli K-12 at 1.95 A resolution. GGT has a stacked alphabetabetaalpha fold comprising the large and small subunits, similar to the folds seen in members of the N-terminal nucleophile hydrolase superfamily. The active site Thr-391, the N-terminal residue of the small subunit, is located in the groove, from which the pocket for gamma-glutamyl moiety binding follows. We have further determined the structure of the gamma-glutamyl-enzyme intermediate trapped by flash cooling the GGT crystal soaked in glutathione solution and the structure of GGT in complex with l-glutamate. These structures revealed how the gamma-glutamyl moiety and l-glutamate are recognized by the enzyme. A water molecule was seen on the carbonyl carbon of the gamma-glutamyl-Thr-391 Ogamma bond in the intermediate that is to be hydrolyzed. Notably the residues essential for GGT activity (Arg-114, Asp-433, Ser-462, and Ser-463 in E. coli GGT) shown by site-directed mutagenesis of human GGT are all involved in the binding of the gamma-glutamyl moiety. The structure of E. coli GGT presented here, together with sequence alignment of GGTs, may be applicable to interpret the biochemical and genetic data of other GGTs.     

Adiponectin produced in coronary circulation regulates coronary flow reserve in nondiabetic patients with angiographically normal coronary arteries

BACKGROUND: Epicardial adipose tissue expresses adiponectin protein, and its expression is significantly lower in patients with severe coronary artery disease (CAD) than in those without CAD. Transcoronary adiponectin levels are significantly decreased in nondiabetic but not in diabetic patients with CAD. Adiponectin is also an important adipocytokine that is linked to insulin resistance and reduces coronary microvascular function. HYPOTHESIS: Adiponectin may play a significant role in the localized coronary circulation. The present study examines the local dynamics of adiponectin in the coronary circulation in nondiabetic individuals with normal coronary arteries and the relationship between adiponectin and coronary microvasculature function. METHODS: We examined 22 consecutive nondiabetic patients whose coronary arteries were angiographically normal. Plasma levels of adiponectin were measured in blood samples that were simultaneously collected from the orifice of the left coronary artery (LCA) and the great cardiac vein (GCV). To evaluate the function of the coronary microcirculation, we measured coronary flow velocity at maximal hyperemia using a Doppler wire. Coronary flow reserve (CFR) was obtained from the ratio of hyperemia to the baseline coronary flow velocity. RESULTS: Plasma adiponectin levels in the GCV (median 6.95 microg/ml) were significantly higher than those in the LCA (median 6.60 microg/ml, p < 0.0005). The difference in plasma adiponectin levels between GCV and LCA significantly correlated with CFR (R = 0.451, p < 0.05). CONCLUSIONS: Adiponectin is locally produced in the coronary circulation. This protein may participate in modulating the coronary circulation of nondiabetic patients with angiographically normal coronary arteries.     

Geographic distribution of fluoroquinolone-resistant Escherichia coli strains in Asia

Fluoroquinolone (FQ) resistance is usually caused by point mutations within the quinolone resistance-determining regions (QRDRs) of gyrA, gyrB, parC and/or parE. However, little is known about the worldwide increase in FQ-resistant Escherichia coli or, more specifically, about the geographical distribution of QRDR mutations and the clonal spread of isolates. In this study, we analysed 68 FQ-resistant E. coli isolates from eight Asian countries using QRDR amino acid mutation patterns and examined their susceptibility to FQs. Of the isolates, 38% had mutations at S83 and D87 of GyrA and S80 of ParC (MM/?/M?/?) and 34% had mutations at S83 and D87 of GyrA, S80 of ParC and S458 of ParE (MM/?/M?/M). MIC₅₀ values (minimum inhibitory concentrations for 50% of the isolates) for isolates with at least mutation at S458 of ParE for ciprofloxacin and prulifloxacin were relatively higher than MIC₅₀ values of isolates without this mutation. Based on their geographic distribution and the QRDR mutation patterns, the isolates were divided into a common type in which the organisms were isolated from three or more countries, and a local type in which the isolates were from one or two countries. Mutation types at S83L and D87N in GyrA and S80I in ParC with no or another site in the QRDR were the most frequent among the FQ-resistant isolates, especially among the common type. Gene typing indicated that isolates in the common type were not similar between countries. These data suggest that the increase in FQ-resistant E. coli strains is mainly generated by mutations in the QRDR in each geographical area rather than through intercontinental spread.