Aims/hypothesis
High fasting blood glucose is one of the well-known risk factors for CHD. However, in certain settings, patients cannot always be expected to fast. For example, community screenings ...for cardiovascular disease (CVD) risk factors in Japan are performed under non-fasting conditions to achieve high participation rates. Thus, we examined a representative cohort of the Japanese population (
n
= 9,444, follow-up period 17.3 years) to clarify whether high casual blood glucose (CBG) can predict CVD mortality.
Methods
We defined CBG groups as follows: high CBG ≥ 11.1 mmol/l or participants with a history of diabetes mellitus; borderline high, 7.77 ≤ CBG < 11.1 mmol/l; higher normal, 5.22 ≤ CBG < 7.77 mmol/l); and lower normal, CBG < 5.22 mmol/l. The multivariate-adjusted hazard ratios (HRs) for CHD, CVD and all-cause mortality were calculated.
Results
The crude CHD mortality rate was 0.84 per 1,000 person-years. Age- and sex-adjusted HRs for CHD mortality were high among participants with CBG levels ≥ 7.77 mmol/l, regardless of time since last meal. Multivariate-adjusted HRs (95% CI) of CHD mortality in high and borderline high CBG groups were 2.62 (1.46–4.67) and 2.43 (1.29–4.58), respectively. Similar results were observed for both CVD and all-cause mortality. Even within the normal blood glucose range, each 1 mmol/l increase in CBG was associated with a statistically significant increase in the HR for CVD mortality (1.12, 95% CI 1.02–1.22). Population-attributable fractions of the combined groups of high and borderline high CBG for CHD, CVD and all-cause mortality were 12.0, 4.9 and 3.5%, respectively.
Conclusions/interpretation
Increases in CBG, even within the normal range, predict CVD mortality.
Nasutitermes takasagoensis soldiers defend their colonies using characteristic diterpenes. Diterpenes are thought to be synthesized in the frontal gland cells surrounding the gland reservoir. To ...identify the genes involved in diterpene synthesis, a cDNA library was prepared from the frontal gland cells and exhaustively sequenced using a 454 pyrosequencer (GS Junior; Roche, Branford, CT, USA). A total of 50 290 clean sequences were assembled into 1111 contigs, which were grouped into 774 genes (isogroups). Based on sequence similarity with known proteins, we identified seven genes encoding the following four enzymes associated with diterpene synthesis: 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) synthase (HMGS), HMG‐CoA reductase (HMGR), farnesyl diphosphate synthase, and geranylgeranyl diphosphate synthases. The expression levels of two enzymes, HMGS and HMGR, involved in the mevalonate pathway were examined, assuming that the site of the defensive terpenoid synthesis strongly activates the mevalonate pathway, which produces a precursor of terpenoids. Real‐time quantitative reverse‐transcriptase PCR confirmed significantly higher expression of HMGS and HMGR in the heads of soldiers. We then divided the head into three parts and found that the expression levels of HMGS and HMGR were significantly higher in the part containing class 1 secretory cells of the frontal gland. Overall, the results suggested that the mevalonate pathway for diterpene synthesis occurs in class 1 cells around the frontal gland reservoir.
A proximity focusing ring imaging Cherenkov detector, with the radiator consisting of two or more aerogel layers of different refractive indices, has been tested in 1–
4
GeV
/
c
pion beams at KEK. ...Essentially, a multiple refractive index aerogel radiator allows for an increase in Cherenkov photon yield on account of the increase in overall radiator thickness, while avoiding the simultaneous degradation in single photon angular resolution associated with the increased uncertainty of the emission point. With the refractive index of consecutive layers suitably increasing in the downstream direction, one may achieve overlapping of the Cherenkov rings from a single charged particle. In the opposite case of decreasing refractive index, one may obtain well separated rings. In the former combination an approximately 40% increase in photon yield is accompanied with just a minor degradation in single photon angular resolution. The impact of this improvement on the
π
/
K
separation at the upgraded Belle detector is discussed.
The aims of this phase I/II study of docetaxel and S-1 were to determine the dose-limiting toxicity (DLT), maximum-tolerated dose (MTD), and recommended dose (RD) in the phase I part and to explore ...the tumour response, survival and safety in the phase II part. Patients with histologically- or cytologically confirmed unresectable or recurrent gastric cancer were eligible. Treatment consisted of intravenous docetaxel on day 1 (starting dose 50 mg m(-2)) and oral S-1 at a fixed dose of 40 mg m(-2) twice daily on days 1-14, every 4 weeks up to six cycles. Nine patients took part in the phase I portion of the study. The MTD of docetaxel was determined to be 50 mg m(-2), with the DLTs of grade 3 infection associated with grade 3 neutropenia and grade 4 neutropenia during S-1 administration. The RD of docetaxel was 40 mg m(-2) in combination with S-1 40 mg m(-2) b.i.d. The efficacy and safety of this regimen was therefore assessed in 46 patients with at least one measurable lesion. The overall response rate and estimated median overall survival were 46% (95% CI, 31-61%) and 14.0 months (8.3-17.3 months), respectively. The most common grade 3/4 toxicity was neutropenia (67% of patients), which was predictable and manageable. This regimen showed promising activity with moderate toxicities in advanced gastric cancer.
Objective: This study is to examine the relationship between dietary selenium intake and 24-h urinary selenium excretion in Japanese population samples participating in the INTERMAP Study. Methods: ...Using highly standardized methods, we assessed individual dietary selenium intake from four 24-h dietary recalls and measured urinary selenium excretion in two timed 24-h urine collections in 1145 Japanese participants (574 men and 571 women) ages 40-59 years in four areas of Japan. Results: The medians of dietary selenium intake were 177.5 micrograms/day in men and 139.8 micrograms/day in women; the medians of 24-h urinary selenium excretion were 127.9 micrograms/day in men and 109.4 micrograms/day in women, that is, urinary excretion was estimated to be 73% of dietary intake in men and 77% in women. Dietary selenium intake was significantly correlated with 24-h urinary selenium excretion (r=0.24 in men, r=0.18 in women; P<0.001). With dietary selenium intake and urinary selenium excretion expressed per kg of body weight, values were similar for men and women (dietary intake, 2.7 micrograms/kg body weight in men and 2.5 micrograms/kg body weight in women; urinary excretion, 2.0 micrograms/kg body weight in men and 2.0 micrograms/kg body weight in women). Conclusion: Dietary intake and 24-h urinary excretion of selenium are related in the Japanese adult population.
Alkaline-heat-treated titanium self-forms an apatite surface layer in vivo. The aim of the present study was to materialistically characterize the surface of alkaline-heat-treated titanium immersed ...in simulated body fluid (AHS-TI) and to examine the differentiation behavior of osteoblasts on AHS-TI. SEM, thin-film XRD, FTIR, and XPS analyses revealed that AHS-TI contained a 1.0-μm-thick, low-crystalline, and 002 direction-oriented carbonate apatite surface. Human osteoblast-like SaOS-2 cells were cultured on polystyrene, titanium, and AHS-TI, and RT-PCR analyses of osteogenic differentiation-related mRNAs were conducted. On AHS-TI, the expression of bone sialoprotein mRNA was up-regulated as compared with that on polystyrene and titanium (p < 0.05). On AHS-TI, the expression of osteopontin and osteocalcin mRNAs was up-regulated as compared with that on polystyrene (p<0.05). The results indicate that the apatite was bone-like and accelerated the osteogenic differentiation of SaOS-2, suggesting that alkaline-heat treatment might facilitate better integration of titanium implants with bone.
Adenosine triphosphate (ATP) is a well-known energy source for muscle contraction. In this study, to visualize localization of ATP, a luciferin-luciferase reaction (LLR) was performed in mouse ...skeletal muscle with an “in vivo cryotechnique” (IVCT). First, to confirm if ATP molecules could be trapped and detected after glutaraldehyde (GA) treatment, ATP was directly attached to glass slides with GA, and LLR was performed. The LLR was clearly detected as an intentional design of the ATP attachment. The intensity of the light unit by LLR was correlated with the concentration of the GA-treated ATP in vitro. Next, LLR was evaluated in mouse skeletal muscles with IVCT followed by freeze-substitution fixation (FS) in acetone-containing GA. In such tissue sections the histological structure was well maintained, and the intensity of LLR in areas between muscle fibers and connective tissues was different. Moreover, differences in LLR among muscle fibers were also detected. For the IVCT-FS tissue sections, diaminobenzidine (DAB) reactions were clearly detected in type I muscle fibers and erythrocytes in capillaries, which demonstrated flow shape. Thus, it became possible to perform microscopic evaluation of the numbers of ATP molecules in the mouse skeletal muscles with IVCT, which mostly reflect living states.
A cell surface heterodimer Toll-like receptor 4 (TLR4)/MD-2 senses lipopolysaccharide (LPS), a principal membrane component of Gram-negative bacteria. LPS binds to MD-2 and induces dimerization of ...TLR4/MD-2. Dimerized TLR4 activates downstream signaling. TLR4 polymorphism replacing Asp299 with Gly and Thr399 with Ile (D299G/T399I) causes LPS hyporesponsiveness, and is associated with a variety of infectious and noninfectious diseases. However, a molecular mechanism underlying the LPS hyporesponsiveness remains controversial. We here asked whether the TLR4 polymorphism influenced cell surface expression of TLR4/MD-2, ligand-dependent TLR4/MD-2 dimerization or TLR4/MD-2 responses to a weak agonist monophosphoryl lipid A (MPL). A newly established anti-TLR4 mAb detected D299G/T399I TLR4/MD-2 on Ba/F3 cells, whereas a previous anti-TLR4 mAb did will this fit on the line above?, suggesting that the D299G/T399I polymorphism caused a conformational change in TLR4. Hyporesponsiveness of D299G/T399I TLR4/MD-2 was much more apparent when cells were stimulated with MPL than with lipid A. MPL-dependent TLR4/MD-2 dimerization was impaired by the D299G/T399I polymorphism. The D299G/T399I polymorphism did not alter LPS-binding to soluble TLR4/MD-2, but impaired its dimerization. These results suggest that the D299G/T399I TLR4 polymorphism impairs TLR4/MD-2 responses by altering ligand-dependent dimerization.
Annual catches of Todarodes pacificus in Japan have gradually increased since the late 1980s. Paralarval abundances have also been higher since the late 1980s compared to the late 1970s and ...mid-1980s. Here is proposed a possible scenario for the recent stock increase based on changing environmental conditions. Based on trends in annual variations in stock and in larval abundances, catches are reviewed and potential spawning areas inferred, assuming that egg masses and hatchlings occur over the continental shelf at temperatures between 15 and 23°C. Changes are then inferred in the spawning areas during 1984–1995, based on GIS data. Since the late 1980s, the autumn and winter spawning areas in the Tsushima Strait and near the Goto Islands appear to have overlapped, and winter spawning sites seem to have expanded over the continental shelf and slope in the East China Sea.
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