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Cardiac arrest occurred in an 85-year-old female administered osimertinib for advanced lung cancer expressing epidermal growth factor receptor (EGFR) mutations. Electrocardiogram (ECG) recorded at recurrence of spontaneous circulation showed sinus rhythm associated with mild QT prolongation (QTc = 455 ms) to which silent myocardial ischemia and coadministration of itraconazole and herbal drug causing hypokalemia (2.1 mEq/L) may have contributed. Discontinuation of osimertinib, itraconazole and herbal drug, potassium supplementation and percutaneous coronary intervention alleviated QT prolongation (QTc = 432 ms). Osimertinib is the third-generation tyrosine kinase inhibitor lengthening QT interval, and careful monitoring of ECG, serum potassium and drugs coadministered during chemotherapy including osimertinib are highly required., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kondo, Kisanuki, Kokawa, Gohara, Kawano, Kagiyama, Maruyama, Odashiro and Maehara.)

The gene products of two members of the EXT (exostosin) gene family, EXT1 and EXT2, function together as a polymerase in the biosynthesis of heparan sulfate. EXTL2 (EXT-like 2), one of the three EXTL genes in the human genome that are homologous to EXT1 and EXT2, encodes an N-acetylhexosaminyltransferase. We have demonstrated that EXTL2 terminates chain elongation of GAGs (glycosaminoglycans), and thereby regulates GAG biosynthesis. The abnormal GAG biosynthesis caused by loss of EXTL2 had no effect on normal development or normal adult homoeostasis. Therefore we examined the role of EXTL2 in CCl4 (carbon tetrachloride)-induced liver failure, a model of liver disease. On the fifth day after CCl4 administration, the liver/body weight ratio was significantly smaller for EXTL2-knockout mice than for wild-type mice. Consistent with this observation, hepatocyte proliferation following CCl4 treatment was lower in EXTL2-knockout mice than in wild-type mice. EXTL2-knockout mice experienced less HGF (hepatocyte growth factor)-mediated signalling than wild-type mice specifically because GAG synthesis was altered in these mutant mice. In addition, GAG synthesis in hepatic stellate cells was up-regulated during liver repair in EXTL2-knockout mice. Taken together, the results of the present study indicated that EXTL2-mediated regulation of GAG synthesis was important to the tissue regeneration processes that follow liver injury.

Mutant alleles of EXT1 or EXT2, two members of the EXT gene family, are causative agents in hereditary multiple exostoses, and their gene products function together as a polymerase in the biosynthesis of heparan sulfate. EXTL2, one of three EXT-like genes in the human genome that are homologous to EXT1 and EXT2, encodes a transferase that adds not only GlcNAc but also N-acetylgalactosamine to the glycosaminoglycan (GAG)-protein linkage region via an α1,4-linkage. However, both the role of EXTL2 in the biosynthesis of GAGs and the biological significance of EXTL2 remain unclear. Here we show that EXTL2 transfers a GlcNAc residue to the tetrasaccharide linkage region that is phosphorylated by a xylose kinase 1 (FAM20B) and thereby terminates chain elongation. We isolated an oligosaccharide from the mouse liver, which was not detected in EXTL2 knock-out mice. Based on structural analysis by a combination of glycosidase digestion and 500-MHz (1)H NMR spectroscopy, the oligosaccharide was found to be GlcNAcα1-4GlcUAβ1-3Galβ1-3Galβ1-4Xyl(2-O-phosphate), which was considered to be a biosynthetic intermediate of an immature GAG chain. Indeed, EXTL2 specifically transferred a GlcNAc residue to a phosphorylated linkage tetrasaccharide, GlcUAβ1-3Galβ1-3Galβ1-4Xyl(2-O-phosphate). Remarkably, the phosphorylated linkage pentasaccharide generated by EXTL2 was not used as an acceptor for heparan sulfate or chondroitin sulfate polymerases. Moreover, production of GAGs was significantly higher in EXTL2 knock-out mice than in wild-type mice. These results indicate that EXTL2 functions to suppress GAG biosynthesis that is enhanced by a xylose kinase and that the EXTL2-dependent mechanism that regulates GAG biosynthesis might be a "quality control system" for proteoglycans.

Many studies have demonstrated that increased carotid intima-media thickness (IMT) is related to future cardiovascular events and is influenced by cardiovascular risk factors such as sex, hypertension, diabetes, and hypercholesterolemia. Although aging is a well-known risk factor for an increase in carotid IMT, few studies have investigated which factors influence carotid IMT in the very elderly. In the present study, we investigated the relationship of pulse pressure (PP), blood pressure (BP), and its variability (six consecutive visits) with carotid IMT among 240 high-risk elderly in whom risk factors were managed clinically (average age was 79 ± 5 years). In the simple correlation, mean systolic BP (SBP) had a positive correlation with IMT and max IMT (P = .012 and P = .045), as did PP (P = .018 and P = .004), but did not diastolic BP or standard deviation of BP and coefficient of variation of BP. In multiple regression analyses, mean SBP and mean PP were each determinants of both IMT and max IMT, when each parameter was added separately to the regression model. We concluded that high SBP and wide PP still have an influence on increased carotid IMT in the very elderly Japanese patients.

Since little is known about the very elderly population aged 80 years and older, we evaluated the association of quality of life (QoL) in an 85-year-old population with physical fitness measurements assessed at age 80 and 85 years. Two hundred seven individuals (90 males, 117 females) aged 85 years underwent the Short Form-36 (SF-36) questionnaires for QoL assessment and physical fitness measurements (handgrip strength, leg-extensor strength, one-leg standing time, stepping rate of legs, walking speed). In 85-year-olds, significant associations were found, by multiple regression analysis or logistic regression analysis, with adjustment for various influencing factors in QoL assessed by SF-36 with physical fitness measurements examined at the age of 85 and 80 years. Physical scales and scores in SF-36, such as physical functioning (PF), limitation in role functioning for physical reasons (role physical; RP), bodily pain (BP), and the physical component score (PCS) tended to be more tightly associated with fitness measurements than mental scales and scores such as limitation in role functioning for emotional reasons (role emotional; RE), and emotional well-being (mental health; MH), and mental component score (MCS). Three scales the general health perceptions (GH), the vitality (VT), and the social functioning (SF) consisting of both physical and mental components were associated with fitness, the extent being intermediate between physical scales and mental scales. Of the several physical fitness measurements, leg-extensor strength and the walking speed of 85-year-olds, and the stepping rate of 80-year-olds were most closely associated with QoL. In a very elderly population of 85- and 80-year-olds, significant associations were found between QoL by SF-36 and physical fitness measurements, suggesting that increases in the levels of physical fitness, even in the very elderly, can contribute to improvements in QoL., (Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.)

A new multimetal complexation system that can change its complexation behavior by C-C bond formation has been developed. The acyclic tetraoxime ligand H(4)L(1) having two terminal allyl groups was synthesized. The olefin metathesis of H(4)L(1) selectively produced trans-H(4)L(2) while the reaction of [L(1)Zn(2)Ca] exclusively afforded cis-H(4)L(2). The saturated analogue H(4)L(3) was synthesized by hydrogenation. The complexation of the ligands H(4)L (L = L(1), trans-L(2), cis-L(2), L(3)) with zinc(II) acetate (3 equiv) yielded the trinuclear complexes [LZn(3)] with a similar trinuclear core bridged by acetato ligands. Whereas the formation process of [L(1)Zn(3)] having an acyclic ligand was highly cooperative, the macrocyclic analogues [LZn(3)] (L = trans-L(2), cis-L(2), L(3)) were formed in a stepwise fashion via the intermediate 2:3 complex [(HL)(2)Zn(3)]. The trinuclear complexes [LZn(3)] (L = L(1), trans-L(2), cis-L(2), L(3)) can recognize alkaline earth metal ions via site-selective metal exchange. The acyclic [L(1)Zn(3)] selectively recognizes Ca(2+), while the cyclic [trans-L(2)Zn(3)] showed a Ba(2+) selectivity. The metal exchange of [LZn(3)] (L = L(1), trans-L(2), cis-L(2), L(3)) with La(3+) efficiently occurred to give [LZn(2)La], but the trans-olefin linker of the [trans-L(2)Zn(2)La] significantly deforms the structure in such a way that one of the salicylaldoxime moieties does not participate in the coordination. Consequently, the chemical transformation of the olefinic moiety significantly affects the multimetal complexation behavior of the tetraoxime ligands.

Large clinical trials have shown that mineralocorticoid receptor (MR) antagonists improve cardiovascular or total mortality in patients with heart failure or myocardial infarction even though the patients were taking angiotensin-converting enzyme inhibitors or angiotensin II receptor (AT1R) antagonists. We previously reported that cardiac fibrosis induced by aldosterone and salt (Ald-NaCl) was exaggerated in AT1aR knockout mice (AT1aR-KOs). As the association of Rho kinase and oxidative stress was reported in Ald-NaCl-induced hypertension of rats, we investigated the effects of an MR antagonist (eplerenone) and a Rho kinase inhibitor (fasudil) on Ald-NaCl-induced cardiac fibrosis in AT1aR-KOs. AT1aR-KOs were administered aldosterone (0.15 microg/h) subcutaneously using an osmotic minipump and were provided with 1% NaCl drinking water for 4weeks. AT1aR-KOs receiving Ald-NaCl were treated with a low (30 mg/kg/day) or high (100mg/kg/day) dose of eplerenone or a fasudil (100mg/kg/day). Systolic blood pressure (SBP), left ventricular weight/body weight (LVW/BW), histological examination and cardiac gene expression were evaluated on day 28. Ald-NaCl treatment caused increases in SBP and LVW/BW in AT1aR-KOs, and eplerenone dose-dependently decreased SBP, LVW/BW and cardiac fibrosis. Fasudil decreased LVW/BW and cardiac fibrosis without affecting SBP. The expressions of connecting tissue growth factor (CTGF) and nicotinamide adenine dinucleotide phosphate (NADPH) components (p22phox, p47phox and p67phox) were increased in Ald-NaCl-treated AT1aR-KOs, and eplerenone or fasudil decreased the expression of CTGF and NADPH components. Phosphorylated ERM (a marker of the phosphorylation of Rho kinase) was increased in Ald-NaCl-treated AT1aR-KOs and was decreased by eplerenone. Nitrotyrosine and 4-hydroxy-2-nonenal, which indicate tissue damage via oxidative stress, were increased in AT1aR-KO and were apparently attenuated by eplerenone or fasudil. These results suggested that the Rho kinase pathway was activated to induce cardiac fibrosis by Ald-NaCl via MR in AT1aR-KOs. A Rho kinase inhibitor as well as eplerenone might be useful for cardiac damage by Ald-NaCl., (Copyright 2009 Elsevier B.V. All rights reserved.)

Background and Aims: Although serum albumin levels are associated with mortality in non-institutionalized elderly people under 80 years old, as well as in the institutionalized very elderly, little is known about the relationship in community-dwelling very elderly people. We, therefore, examined the association in a Japanese population of 80-year-old community residents., Methods: Serum albumin levels were measured in 672 (267 men, 405 women) out of 1282 80-year-old individuals. Over the following 4 years, the dates and causes of death were recorded from resident registration cards and official death certificates., Results: Of the above individuals, 107 subjects died (58 men, 49 women: 27 due to cancer, 27 cardiovascular disease, and 22 pneumonia). Survival rates were compared among 4 groups (highest >or=45 g/L, higher than 43-44 g/L, lower than 41-42 g/L, lowest

Immunodeficient animals are in demand in current biomedical research, and they contribute to medical progress. In Pneumocystis infections, a specific histological diagnostic tool may be immunochemistry (IC). However, it was recently reported that the antibody (3F6) was not suitable for detecting Pneumocystis in rats. We purchased another antibody [PNC007] from a commercial source for IC. We could detect positive signals at identical locations with IC and Toluidine blue O in lungs of infected rats. These results corresponded to the results obtained with PCR. We should study the relationship between unexpected positive signals seen in IC and trophic forms in lungs of infected rats. We could clinically diagnose pneumonia caused by Pneumocystis carinii with the diagnostic method we developed.

Hypertension is one of the greatest risk factors for cardiovascular disease, but its contribution to cardiovascular mortality weakens with aging. We have previously demonstrated that at the age of 80, higher systolic blood pressure (SBP) is not correlated with increased mortality in Japan. However, we did not examine in detail whether diastolic blood pressure (DBP) independently affects mortality. In the present study, 639 participants, who were 80 years old in 1997, were enrolled. The subjects were divided by their DBP [below 70 mmHg (group 1, n = 136), from 70 mmHg to 80 mmHg (group 2, n = 200), from 80 mmHg to 90 mmHg (group 3, n = 194), over 90 mmHg (group 4, n = 109)]. During the 4-year follow-up period, 90 individuals died. Cox multivariate regression analysis revealed that group 1 showed a significantly higher mortality rate than group 4 [relative risk (RR) 2.47, confidence interval (CI) 1.07-5.70, p = 0.03)]. The relative risks of deaths from cardiovascular diseases, pneumonia, and cancer tended to be higher in group 1 than in group 4, but the difference did not reach statistical significance. These results suggest that decreased DBP is associated with higher mortality in the Japanese elderly.

Background: Increased salt intake may induce hypertension, lead to cardiac hypertrophy, and exacerbate heart failure. When elderly patients develop heart failure, diastolic dysfunction is often observed, although the ejection fraction has decreased. Diabetes mellitus (DM) is an established risk factor for heart failure. However, little is known about the relationship between cardiac function and urinary sodium excretion (U-Na) in patients with DM., Methods: We measured 24-hour U-Na; cardiac function was evaluated directly during coronary catheterization in type 2 DM (n = 46) or non-DM (n = 55) patients with preserved cardiac systolic function (ejection fraction > or = 60%). Cardiac diastolic and systolic function was evaluated as - dp/dt and + dp/dt, respectively., Results: The average of U-Na was 166.6 +/- 61.2 mEq/24 hour (mean +/- SD). In all patients, stepwise multivariate regression analysis revealed that - dp/dt had a negative correlation with serum B-type natriuretic peptide (BNP; beta = - 0.23, P = .021) and U-Na (beta = - 0.24, P = .013). On the other hand, + dp/dt negatively correlated with BNP (beta = - 0.30, P < .001), but did not relate to U-Na. In the DM-patients, stepwise multivariate regression analysis showed that - dp/dt still had a negative correlation with U-Na (beta = - 0.33, P = .025)., Conclusion: The results indicated that increased urinary sodium excretion is associated with an impairment of cardiac diastolic function, especially in patients with DM, suggesting that a reduction of salt intake may improve cardiac diastolic function.

Aim: Helicobacter pylori (HP) has been implicated as a risk factor for cardiovascular and atherosclerotic diseases. Arterial stiffness determined by pulse wave velocity (PWV) or the cardio-ankle vascular index (CAVI) has been shown to be higher in HP-positive subjects than in HP-negative subjects; however, this result has been observed only in young subjects. The aim of the study was to investigate the possible correlation between HP infection and PWV or CAVI in middle-aged subjects., Methods: We measured brachial-ankle PWV (baPWV), CAVI, metabolism markers, pepsinogens (PGs) and IgG antibody to HP in 343 individuals aged either 60 or 65 year old. Atrophic gastritis (AG) was diagnosed based on the values of PGs., Results: baPWV and CAVI were significantly higher in the AG-positive group than in the AG-negative group even after adjusting for possible confounding factors (baPWVc; 16.63+/-3.50 vs. 15.59+/-3.47 p=0.010, CAVIc; 8.59+/-1.20 vs. 8.27+/-1.19 p=0.022). baPWV and CAVI values tended to be higher in the HP-positive group than in the HP-negative group. High-density lipoprotein (HDL) cholesterol level and the adiponectin level were lower in the AG-positive group than in the AG-negative group., Conclusion: There may be an association between atrophic gastritis and atherosclerosis in middle-aged subjects.

Background: Immunoglobulin levels are elevated in the older people. However, it is unknown whether these levels are related to mortality., Object: To evaluate the association between immunoglobulin levels and mortality., Methods: The study population included 697 individuals (277 males and 420 females) of 1,282 eighty-year-old individuals residing in the Fukuoka prefecture, Japan. The participants were followed for 4 years after the baseline examination., Results: The hyper-IgA group, defined as a serum IgA level >400 mg/dl, had high mortality using Kaplan-Meier analysis (log rank, p=0.037). Multivariate Cox regression analyses revealed a high risk of mortality (hazard rate=1.233, 95% confidence interval 1.109-1.491, p=0.031) after adjusting for covariates. The high risk of mortality in the hyper-IgA group was significant in males, but not in females. Moreover, Kaplan-Meier analysis revealed that IgA was related to cancer mortality in males (log rank, p=0.031), but not to pneumonia or cardiovascular disease. IgM and IgG levels were not related to high risk of mortality., Conclusion: Serum IgA levels appear to be a predictor of mortality, especially cancer mortality in males., (Copyright 2008 S. Karger AG, Basel.)

Chronic kidney disease (CKD) is one of the greatest risk factors for cardiovascular disease (CVD). The contribution of CKD to CVD mortality is not well understood in very elderly patients. Our study examined whether CKD might be a risk factor for total and CVD mortality in very elderly Japanese individuals. A total of 621 participants were enrolled, all of whom were 80 years old. The subjects were divided on the basis of the presence (CKD(+) group, n=280) or absence (CKD(-) group, n=341) of CKD. CKD was defined by as an estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m(2). The eGFR of the CKD(+) and CKD(-) groups was 49.7+/-8.5 and 70.9+/-9.5 mL/min/1.73 m(2), respectively. During the 4-year study period, 87 individuals died, and 25 of those deaths were due to CVD. A Cox multivariate regression analysis revealed no association between total mortality and CKD (relative risk [RR] 1.17, confidence interval [CI] 0.75-1.82, p=0.50). However, the CVD mortality was significantly increased in the CKD(+) group (RR 4.60, CI 1.69-12.52, p=0.003). CKD significantly increased the CVD mortality in subjects who were not taking antihypertensive medication (RR 5.15, CI 1.04-25.50, p=0.04). Our results suggest that CKD increases the risk of CVD mortality in very elderly individuals. It is not only important to prevent progression toward CKD in patients who do not suffer from CKD, but also critical to manage the risk factors for CVD in patients with CKD, despite their advanced age. (Hypertens Res 2008; 31: 2053-2058).

Objectives: To evaluate the association between high-level functional capacity and chewing in a middle-old community-based population., Background: Although basic and instrumental activities of daily living are known to be associated with chewing ability in the elderly, an association between higher levels of competence and chewing ability has not been evaluated in the elderly., Materials and Methods: The association between chewing ability using a number of different foods and high-level functional capacity by the Tokyo Metropolitan Institute of Gerontology was evaluated in 694, 80-year-old people residing in Fukuoka Prefecture, Japan., Results: A significant correlation was found, using multiple regression or logistic regression analyses adjusted for various confounding factors, between the number of total chewable foods, hard foods or moderately hard foods, and total functional capacity, instrumental activity, intellectual activity or social role ability. In contrast, the number of slightly hard foods, easily chewable foods and remaining teeth were only partly related to total functional capacity and intellectual activity., Conclusion: High-level functional capacity including intellectual activity and social role in middle-old elderly was associated with the ability to chew hard foods than to chew easily chewable foods. Maintenance of chewing ability in elderly might result in better intellectual activity and social role.

This study examined the relationship between volatile sulfur compounds (VSCs), including hydrogen sulphide (H(2)S), methyl mercaptan (CH(3)SH) and dimethyl sulphide [(CH(3))(2)S], in mouth air of patients and a history of systemic disease. The subjects were 387 residents (174 males and 213 females) of Fukuoka Prefecture, Japan, who participated in an oral and systemic health survey for elderly persons (mean age: 61.8, s.d. 2.8 years). The VSCs were measured using a portable gas chromatograph (OralChroma). The H(2)S concentrations were significantly greater in the 132 subjects with a history of hypertension and the 41 subjects with a history of respiratory disease, including pneumonia, pulmonary emphysema and bronchitis, than in those without such a history. The CH(3)SH concentrations were significantly greater in those with a history of hypertension. The 16 subjects with a history of cerebrovascular disease, including intracerebral haemorrhage, cerebral infarction, and subarachnoid haemorrhage, and the 58 subjects with a history of liver disease, including hepatitis, alcoholic liver disease, drug-induced liver injury, fatty liver and liver cirrhosis, showed significantly greater (CH(3))(2)S concentrations (p < 0.05). These results suggest an association between the production of VSCs in mouth air and systemic diseases such as hypertension as well as respiratory, cerebrovascular and liver diseases.

Hypertension is one of the greatest risk factors for cardiovascular disease, but the contribution of high blood pressure to cardiovascular morbidity and mortality is weakened with aging. In the present study, we examined whether high blood pressure would be a risk factor for total and cardiovascular mortality in a group of very elderly Japanese. Six hundred and thirty-nine participants who were 80 years old in 1997 were enrolled. The subjects were divided into three groups on the basis of their systolic blood pressure (SBP) (below 140 mmHg [group 1, n=212], from 140 mmHg to 159 mmHg [group 2, n=217], over 160 mmHg [group 3, n=210]). During the 4-year follow-up period, 87 individuals died and 24 of these deaths were due to cardiovascular diseases. Cox multivariate regression analysis revealed that there was no association between total mortality and SBP levels (relative risk [RR] 1.71; confidence interval [CI] 0.81-3.58; group 3 compared with group 1, p=0.35). However, the subjects taking antihypertensive medication showed significantly higher mortality with increasing SBP level (RR 5.72, CI 1.03-31.6, p=0.04, group 3 compared with group 1). Furthermore, in the subjects with a cardiovascular disease such as angina or stroke, high SBP increased the total mortality (RR 13.4, CI 2.39-75.1, p=0.004, group 3 compared with group 1). The present study did not find an association between blood pressure and mortality in the very elderly. However, our results did suggest that high SBP increases the risk of mortality in patients with cardiovascular diseases and/or taking antihypertensive medication.

Background: Little is known about the association between physical fitness and cognitive function in very elderly people (over 80 years of age)., Objectives: To evaluate that relationship in 85-year-old community-dwelling individuals., Methods: Out of 207 participants (90 males, 117 females) who were 85 years old and community-dwelling, 205 completed the Mini-Mental State Examination (MMSE) for evaluating cognitive function. The numbers of subjects who completed physical fitness measurements such as hand-grip strength, isometric leg extensor strength, one-leg standing time, stepping rate, and walking speed were 198, 159, 169, 168, and 151, respectively., Results: There were significant associations in MMSE with hand-grip strength (right or left hand), isometric leg extensor strength, stepping rate, and walking speed by simple regression analysis. MMSE was still significantly associated with hand-grip strength (beta = 0.305, p = 0.005 for right side; beta = 0.309, p = 0.004 for left side), stepping rate (beta = 0.183, p = 0.046), and walking speed (beta = -0.222, p = 0.014) by multiple regression analysis after adjustments for the amount of education, gender, smoking, drinking, complication of stroke, body weight, body height, regular medical care, serum albumin, blood HbA1c, and marital status. By logistic regression analysis, the prevalence of a normal MMSE score (MMSE >or=24) was increased by 9% with each 1-kg increase in hand-grip strength of the left hand (OR 1.087, 95% CI 1.003-1.179, p = 0.042), and was increased by 6% with each step per 10 s in stepping rate (OR 1.060, 95% CI 1.000-1.122, p = 0.048)., Conclusion: In a very elderly population of 85-year-olds, cognitive function was associated with some physical fitness measurements, independent of confounding factors., ((c) 2008 S. Karger AG, Basel.)

Background: The relationship between Helicobacter pylori (HP) infection and body mass index (BMI) is controversial. Several reports have indicated that eradication of HP infection induces an increase in BMI. In contrast, epidemiological case-control studies have failed to show an association between HP infection and BMI. Therefore, we investigated whether HP and atrophic gastritis (AG) were associated with BMI., Methods: A total of 617 individuals were recruited for the measurements of BMI, serum leptin, pepsinogens (PGs) I and II, and IgG antibody to HP (HP-IgG). BMI and leptin of the subjects were compared when the subjects were stratified by HP-IgG and PGs., Results: The subjects were divided into AG-positive and AG-negative groups according to PGs (AG-positive: PG I < or = 70 ng/ml and PG I/II ratio < or =3.0). BMI after adjusting for sex and age was significantly lower in the AG-positive group than in the AG-negative group (23.47 +/- 3.05 vs. 24.18 +/- 3.25, P = 0.010). When the subjects were divided into two groups according to HP-IgG, BMI tended to be lower in the HP-IgG-positive group, though the difference was not large. When the subjects were divided into four groups for different combinations of AG and HP-IgG, BMI was the lowest in the AG-positive and HP-IgG-negative group., Conclusions: BMI was associated with AG, as diagnosed by PGs, but not with HP infection status. These results mean that HP infection affects BMI via atrophic gastritis.

An oligometallic template effect was observed on the cis/trans selectivity of a 32-membered macrocyclic tetraoxime in ring-closing olefin metathesis of an acyclic diallyl derivative H4L; the metathesis of heterotrinuclear complex LZn2M (M=Ca2+, La3+) afforded the cis isomer, whereas uncomplexed H4L gave the trans isomer.

Aldosterone infusion with high salt treatment induces cardiac fibrosis in rats. Aldosterone enhanced angiotensin II (Ang II) has been shown to induce proliferation and increase the expression of Ang II receptor mRNA and Ang II binding in vitro. To investigate the role of Ang II type 1a receptor (AT1aR) in aldosterone-and-salt (Ald-NaCl)-induced cardiac fibrosis, we subcutaneously infused aldosterone (0.15 microg/h) and 1% NaCl (Ald-NaCl) into AT1aR knockout mice (AT1aR-KO) or wild type mice (Wt). To examine the role of NaCl on cardiac fibrosis, we gave some of the aldosterone-treated AT1aR-KO tap water (Ald-H2O). Ald-NaCl treatment increased systolic blood pressure and induced cardiac hypertrophy in both strains, whereas there were no such changes in the mice without aldosterone. Severe cardiac fibrosis was seen in Ald-NaCl-treated AT1aR-KO and not in Ald-NaCl-treated Wt. In contrast, Ald-NaCl-treated Wt with co-administration of an active metabolite of olmesartan, the AT1aR antagonist (10 mg/kg/day) did not show cardiac fibrosis. Na+/H+ exchanger, and Na+-K+ ATPase alpha2 subunit mRNA were decreased in AT1aR-KO. Na+/Ca2) exchanger mRNA was lower in AT1aR-KO than Wt and was decreased by Ald-NaCl in both strains. Phosphorylation of epidermal growth factor receptor and extracellular signal-regulated kinase was increased by Ald-NaCl treatment in AT1aR-KO. Connective tissue growth factor (CTGF) and osteopontin mRNA were increased and accumulation of CTGF proteins was seen in the hearts of Ald-NaCl-treated AT1aR-KO. Ald-H2O-treated AT1aR-KO did not show any cardiac fibrosis. These results suggest that Ald-NaCl-induced cardiac fibrosis required both aldosterone and salt. Because cardiac fibrosis was exaggerated in Ald-NaCl-treated AT1aR-KO but was not seen in Wt treated with Ald-NaCl and olmesartan, AT1aR may not play a primary role in progression of cardiac fibrosis by Ald-NaCl, and gene disruption of AT1aR may have some implications in this model.

Background: Because little is known about the relationship between physical fitness and mortality among very elderly people, we evaluated this association in a Japanese population of 80-year-old community residents., Methods: Among 1282 80-year-old residents of Fukuoka Prefecture, Japan, 697 individuals (277 men and 420 women) underwent physical fitness tests of handgrip strength, isometric leg extensor strength, isokinetic leg extensor power, stepping rate, and one-leg standing time. Four years later, the dates and causes of death among the participants during those years were analyzed based on data from resident registration cards and from official death certificates., Results: During the 4-year follow-up period, 107 individuals (58 men and 49 women) died. Of these deaths, 27 were due to cardiovascular disease (CVD), 27 to cancer, 22 to pneumonia, and the rest to other causes. The relative hazard ratios (HR) for all-cause mortality, adjusted for various confounding factors, fell with increases in stepping rate, and the HR for pneumonia mortality fell with increases in leg extensor strength. In contrast, there was no association between cardiovascular or cancer mortality and physical fitness., Conclusions: A partial association was found between impaired physical fitness at the age of 80 years and increased mortality in the 4 years thereafter. Mortality due to all causes was related only to stepping rate, and mortality due to pneumonia was related to leg extensor strength. Mortality due to CVDs or cancers was not associated with physical fitness.

Objectives: To evaluate the association between body mass index (BMI) and all-cause mortality and cardiovascular disease (CVD) in an 80-year-old population., Design: Cohort study., Setting: Community-based., Participants: Six hundred ninety-seven of 1,282 (54.4%) 80-year-old candidate individuals., Measurements: The dates and causes of all deaths were followed up for 4 years., Results: The relative hazard ratios (HRs) for all-cause mortality were lower in overweight subjects (BMI > or= 25.0) than in underweight (BMI<18.5) or normal-weight (BMI 18.5-24.9) subjects. Similarly, the HRs for mortality due to CVD in overweight subjects were 78% less (HR=0.22, 95% confidence interval (CI)=0.06-0.77) than those in underweight subjects, and those in normal weight subjects were 78% less (HR=0.22, 95% CI=0.08-0.60) than those in underweight subjects. Mortality due to CVD was 4.6 times (HR 4.64, 95% CI=1.68-12.80) as high in underweight subjects as in normal-weight subjects, and mortality due to cancers was 88% lower (HR=0.12, 95% CI=0.02-0.78) in the overweight group than in the underweight group. There were no differences in mortality due to pneumonia., Conclusion: Overweight status was associated with longevity and underweight with short life, due to lower and higher mortality, respectively, from CVD and cancer.

The treatment of special types of varices with portal hypertension has not yet been established. We were able to control 13 cases of special types of varices by percutaneous transhepatic obliteration (PTO). These 13 cases consisted of 2 esophagojejunal varices after total gastrectomy for gastric cancer, 1 stoma varices after abdominoperineal excision for rectal cancer, 2 mesenteric varices with encephalopathy, 1 gastric variceal rupture, 1 gastrorenal and gastroazygos shunt with encephalopathy, 3 giant bar-type esophageal varices, 2 isolated gastric varices with gastropericardiac shunts, and 1 isolated gastric varices with gastrophrenic shunt. The special types of varices were successfully embolized in all cases and there were no complications. We conclude that the PTO is still an effective and safe treatment for special types of varices with portal hypertension.

It has been shown that the pressor responses to microinjection of L-glutamate in the rostral ventrolateral medulla (RVLM) are augmented in spontaneously hypertensive rats (SHR), and that these augmented responses are not altered by chronic conventional antihypertensive treatment. The aim of the present study was to determine the effect of chronic oral treatment with a new angiotensin II type 1 (AT(1)) receptor antagonist, RNH-6270 (the active form of olmesartan medoxomil), on cardiovascular responses to excitatory amino acids in the RVLM of SHR. SHR (12 weeks old) were treated with RNH-6270 (30 mg/kg/day) or vehicle for 4 weeks. At 16 weeks of age, L-glutamate (2 nmol), N-methyl-D-aspartate (NMDA; an ionotropic glutamate receptor agonist (20 pmol)), or (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3R)-ACPD; a metabotropic glutamate receptor agonist (1 nmol)) was microinjected into the RVLM of rats. The pressor responses to microinjection of L-glutamate or NMDA in the RNH-6270-treated SHR (+28.3 +/- 1.0 and +48.3 +/- 2.5 mm Hg, respectively) were significantly smaller than those in untreated SHR (+45.7 +/- 2.2 and +69.4 +/- 7.0 mm Hg, respectively, P < 0.05 each); however, they were still greater than those in the Wistar-Kyoto rats (+21.7 +/- 1.0 and +28.6 +/- 3.3 mm Hg, respectively, P < 0.05 each). In contrast, the augmented pressor responses to microinjection of (1S,3R)-ACPD in SHR were not affected by the RNH-6270 treatment. These results demonstrated that chronic oral treatment with RNH-6270, an AT(1) receptor antagonist, partly normalizes the pressor responses to L-glutamate or NMDA, but not (1S,3R)-ACPD, in the RVLM of SHR, suggesting that endogenous angiotensin II may be involved in the exaggerated pressor response to l-glutamate, probably through its ionotropic glutamate receptors.

APJ was cloned as an orphan G protein-coupled receptor and shares a close identity with angiotensin II type 1 receptor (AT1R). Apelin is a peptide that has recently been identified as an endogenous ligand of the APJ. Apelin and APJ mRNA are expressed in peripheral tissue and the central nervous system. However, little is known about the effects of apelin in cardiovascular regulation. To examine the central and peripheral role of apelin, we injected the active fragment of apelin [(Pyr1)apelin-13] intracerebroventricularly (ICV, 5 and 20 nmol, n=6) or intravenously (IV, 20 and 50 nmol, n=4 or 5) in conscious rats. ICV injection of (Pyr1)apelin-13 dose-dependently increased mean arterial pressure (MAP) and heart rate (HR) (19+/-3 mm Hg and 162+/-26 bpm at 20 nmol). Pretreatment with ICV injection of the AT1R antagonist (CV-11974, 20 nmol) did not alter the apelin-induced increase in MAP and HR. IV injection of (Pyr1)apelin-13 also dose-dependently increased MAP and HR (13+/-2 mm Hg and 103+/-18 bpm at 50 nmol); however, the peripheral effects of apelin were relatively weak compared to its central effects. Expression of c-fos in the paraventricular nucleus (PVN) of hypothalamus was increased in the rat that received ICV injection of (Pyr1)apelin-13 but not in the rat that received IV injection of (Pyr1)apelin-13. These results suggest that apelin plays a role in both central and peripheral cardiovascular regulation in conscious rats, and that the cardiovascular effects of apelin are not mediated by the AT1R.

Ghrelin is an orexigenic peptide originally isolated from the stomach. Intracerebroventricular administration of ghrelin has been shown to elicit decreases in arterial pressure and renal sympathetic nerve activity in conscious rabbits. The aim of the present study was to determine the role of ghrelin in the brain stem in cardiovascular responses in rats. Unilateral microinjection of ghrelin into the nucleus of the solitary tract significantly decreased the mean arterial pressure and heart rate (-17.3+/-0.8 mm Hg and -13.6+/-3.5 bpm by 20 pmol). The microinjection of ghrelin into the nucleus of the solitary tract also suppressed the renal sympathetic nerve activity (-29.5+/-3.4%; P<0.0001). Pretreatment with intravenous injection of pentolinium (5 mg/kg), a ganglion-blocking agent, eliminated these cardiovascular responses induced by the microinjection of ghrelin (20 pmol) into the nucleus of the solitary tract; however, pretreatment with intravenous injection of atropine sulfate (0.1 mg/kg), an antagonist of muscarinic acetylcholine receptors, failed to prevent them. In contrast, unilateral microinjection of ghrelin into the area postrema, rostral, and caudal ventrolateral medulla caused no significant changes in the mean arterial pressure and heart rate. On the other hand, immunohistochemical study revealed that the receptor for ghrelin, the growth hormone secretagogue receptor, was expressed in the neuronal cells of the nucleus of the solitary tract and the dorsal motor nucleus of the vagus, but not in the cells of the area postrema. These results suggest that ghrelin acts at the nucleus of the solitary tract to suppress sympathetic activity and to decrease arterial pressure in rats.