[Recommended dietary allowances and nutritional assessments in infants and children].
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Child↗
Biomedical subjects
Y Hirai
Publications and source records attributed to Y Hirai.
[Specialties in parenteral and enteral nutritions in infants and children].
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Amino Acids↗
[Indication and non-indication of parenteral and enteral nutritions in infants and children].
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Child↗
Mutational analysis of BRCA1 and BRCA2 and clinicopathologic analysis of ovarian cancer in 82 ovarian cancer families: two common founder mutations of BRCA1 in Japanese population.
We analyzed genetic alterations in BRCA1 and BRCA2 genes among 82 ovarian cancer families in Japan. The clinical characteristics of BRCA-associated ovarian cancer patients were compared with cases carrying no mutations as well as with population controls. Using a direct sequencing method, 45 of the 82 ovarian cancer families were found to carry BRCA1 or BRCA2 germ-line mutations (40 with BRCA1 and 5 with BRCA2). In 24 independent mutations of BRCA1, 5 recurrent mutations were found and 2 of them, the L63X and Q934X mutations, were detected in seven and eight independent families, respectively. In addition, 16 mutations of BRCA1 and 3 mutations of BRCA2 have never been described previously. In consideration of clinicopathological features, there was a significantly higher proportion of tumors with serous adenocarcinoma and of cases of advanced stages in the BRCA1 or BRCA2 cases than in those of the controls. On the other hand, there were no differences of mean age at diagnosis between patients with BRCA1 or BRCA2 mutation and those of the controls. Our results indicate that the features of BRCA-associated ovarian cancer in Japan appear to be similar to those in Western countries, and the L63X and Q934X mutations of BRCA1 appear to be common founder mutations unique to the Japanese population.
Adolescent↗
Enhanced oncogenicity of human papillomavirus type 16 (HPV16) variants in Japanese population.
To investigate whether HPV16 E6 variants carry an elevated risk for cervical cancer in Japanese population, we investigated the E6 sequence variation in 40 cervical intraepithelial neoplasias (CINs) I-III and 43 invasive cervical cancers (ICCs), all positive for HPV16. HPV16 E6 variants were frequently found in ICCs than in CINs (88 vs. 65%, P=0.01). The E6 D25E, a rare variant in Western countries, was most frequently observed in ICC (44%). CIN I/II lesions with HPV16 variants were less likely to regress than those with HPV16 prototype (P=0.048). The finding that HPV16 E6 variants represent a significant risk factor is common between Western and Japanese women despite the different distribution of each variant.
Base Sequence↗
Palladium(II)-catalyzed cyclization of urethanes and total synthesis of 1-deoxymannojirimycin.
The palladium(II)-catalyzed cyclization of the urethane 8, which was derived from D-mannitol, gave the cyclic compound 9 with excellent diastereoselectivity. During these transformations, the Pd(II) species are not reduced and thus the catalyst can recycle without its reoxidation. The cycloadduct 9 was converted to 1-deoxymannojirimycin.
1-Deoxynojirimycin↗
Regulation of rheumatoid synovial cell growth by ceramide.
Overgrowth of rheumatoid synoviocytes, which results in joint destruction, is due to impaired balance between cell proliferation and cell death (apoptosis). Ceramide is an important lipid messenger involved in mediating a variety of cell functions including apoptosis. We investigated the effects of ceramide on growth-promoting anti-apoptotic signals in rheumatoid synovial cells. Human synovial cells isolated from patients with rheumatoid arthritis (RA) were stimulated with platelet-derived growth factor (PDGF) in the presence or absence of C2-ceramide. The kinase activity of Akt, MEK, and ERK1/2 was analyzed in PDGF-stimulated synovial cells by Western blot analysis. Pretreatment with C2-ceramide completely inhibited PDGF-induced cell cycle progression of rheumatoid synovial cells. PDGF stimulation induced phosphorylation and activation of Akt, MEK, and ERK1/2 in rheumatoid synovial cells. C2-ceramide inhibited the activation of Akt, MEK and ERK1/2 in PDGF-stimulated synovial cells. Our data demonstrated that inhibition of anti-apoptotic kinases, such as Akt and ERK1/2, may play an important role in ceramide-mediated apoptosis of rheumatoid synovial cells.
Apoptosis↗
Induction of COX-2 expression by nitric oxide in rheumatoid synovial cells.
Prostaglandins formed by cyclooxygenase (COX) enzymes are important mediators of inflammation. The contribution of inducible COX-2 in the rheumatoid synovium is well documented. In this study, we evaluated the contribution of nitric oxide (NO) to COX-2 expression in rheumatoid synovial cells. Exposure of rheumatoid synovial cells to a NO donor, SNAP, induced COX-2 protein expression in a dose-dependent manner. RT-PCR analysis also demonstrated that COX-2 mRNA was induced in SNAP-treated synovial cells. Dexamethasone at therapeutic concentrations markedly inhibited this NO-mediated COX-2 expression in synovial cells. In contrast to its effect on COX-2 expression, SNAP did not affect the constitutive expression of COX-1 in rheumatoid synovial cells. Our findings suggest that NO is an important modulator of COX-2 expression and that glucocorticoids exert their anti-inflammatory action in rheumatoid synovium, at least in part, by suppression of COX-2 induction.
Arthritis, Rheumatoid↗
Involvement of spindles of an entomopoxvirus (EPV) in infectivity of the EPVs to their host insect.
The biological function of entomopoxvirus (EPV) spindles (inclusion bodies that lack virions), has not been elucidated. We characterized the function of EPV spindles in the cupreous chafer, Anomala cuprea (Coleoptera: Scarabaeidae). Spheroids or spheroids mixed with spindles of Anomala cuprea EPV were administered per os to the A. cuprea larvae. A significant increase in infectivity was induced by the addition of spindles to the spheroids, strongly suggesting that the spindles play an important role in the infection of the host insect.
Animals↗
19F NMR study of protein-induced rhombic perturbations on the electronic structure of the active site of myoglobin.
A novel C2-symmetric ring-fluorinated hemin, 13,17-bis(2-carboxyethyl)-2,8,12,18-tetramethyl-3,7-difluoroporphyrin atoiron(III), has been synthesized and was incorporated into sperm whale apomyoglobin to investigate protein-induced rhombic perturbations on the electronic structure of the active site of myoglobin (Mb) using 19F NMR spectroscopy. NMR signals for 19F atoms introduced as substituents on the present heme in ferrous low-spin and high-spin and ferric low-spin complexes have been observed and their shifts sharply reflect not only the electronic nature of the heme iron, but also in-plane asymmetry of the heme electronic structure. The two-fold symmetric electronic structure of the ring-fluorinated hemin is clearly manifested in the 19F and 1H NMR spectra of its dicyano complex. The chemical equivalence of the two fluorine atoms of the heme is removed in the active site of myoglobin and the splitting of the two 19F NMR signals provides a quantitative probe for characterizing the rhombic perturbation of the heme electronic structure induced by the heme-protein interaction. The in-plane asymmetry of heme electronic structures in carbon-monoxy and deoxy Mbs have been analyzed for the first time on the basis of the shift difference between the two 19F NMR signals of the heme and is interpreted in terms of iron-ligand binding and/or the orbital ground state of the heme. A potential utility of 19F NMR, combined with the use of a symmetric fluorinated hemin, in characterizing the heme electronic structure of myoglobin in a variety of iron oxidation, spin, and ligation states, is presented.
Animals↗
The role of obesity in the association of cardiovascular risk factors and glucose intolerance in small Japanese and North American communities.
To investigate whether the influence of obesity on cardiovascular risk factors and glucose intolerance differs between Japan and the US, we conducted cross-sectional surveys in those with elevated plasma glucose in Tanushimaru, Japan, and a stratified random population sample, in Wadena, MN. Subjects numbered 204 in Tanushimaru and 334 in Wadena. Body mass index (BMI), blood pressure, blood lipids, fasting plasma levels of glucose, glycosylated hemoglobin A(1c,) insulin, and free fatty acids were assessed. Overweight was defined as BMI of 27.5-29.9 kg/m(2) and obesity as BMI> or =30 kg/m(2). Gradual increases in risk factors were seen as BMI increased in both studies. Most risk factors were associated with glucose intolerance, except for BMI in Tanushimaru. In Wadena, glucose intolerance increased sharply among the obese. Adjustment for BMI attenuated the associations of cardiovascular risk factors with glucose intolerance in Wadena, but not in Tanushimaru. Obesity has an exaggerated influence on risk factors, compared with being overweight. The associations of glucose intolerance with cardiovascular risk factors are more affected by adjustment for BMI in Wadena than in Tanushimaru, not because of a different influence of body weight on risk factors between the two cities, but because obesity is rare in Japan.
Adult↗
Association between alcohol intake and development of hypertension in Japanese normotensive men: 12-year follow-up study.
Although it has been suggested that alcohol intake is related to hypertension, few long-term prospective studies have investigated this relationship. We therefore conducted a prospective study in male residents of a farming community in Japan to determine whether heavy drinking would predispose to the development of hypertension. A total of 325 normotensive (< 140/90 mm Hg) men were enrolled in 1977. Twelve years later, 93 (28.6%) subjects became hypertensive (defined as blood pressure > or = 140/90 mm Hg or use of antihypertensive medication). The probability of the development of hypertension in heavy drinkers predicted from a logistic regression equation was 44.6% (relative risk: 2.05 versus nondrinkers) after adjusting for age and body mass index (BMI). It was 36.2% (relative risk: 1.86 versus nondrinkers) after a further adjustment for systolic blood pressure at baseline. A high odds ratio of 2.39 for the development of hypertension with alcohol intake of < 46 g/day versus > or = 46 g/day at baseline was obtained even after adjustments for age, BMI, and confounding factors. We conclude that habitual heavy drinking of alcohol is a risk factor for the development of hypertension. This is the first report demonstrating a significant relationship between habitual alcohol intake and the development of hypertension in a long-term prospective study in Japan.
Adult↗
The effect of biofiltration on red blood cells 2.3-diphosphoglycerate and pH.
To investigate the effect of biofiltration (BF) on the ability of blood to supply oxygen to the peripheral tissues, a 2 week crossover study was conducted with bicarbonate hemodialysis (BcHD) and BF using 5 male patients with diabetic renal failure as subjects. BcHD and BF were performed for 4 h and 3.5 h per session, respectively. Blood gases, the pH of red blood cells (RBC-pH), and 2. 3-diphosphoglycerate in RBC (RBC-2.3DPG) were measured during each treatment. After a 2 week BF treatment, the plasma HCO3- at the beginning of BF was significantly higher than that of BcHD (p < 0.01), and the blood pH improved with an elevated plasma bicarbonate level (p < 0.05). The RBC-pH at the beginning of BF was higher than that of BcHD (p < 0.05) although the RBC-pH at the end of both therapies increased to similar levels. The RBC-2.3DPG during BcHD remained unchanged, but during BF significantly increased (p < 0.05). Metabolic acidosis was significantly improved by BF with its effect reaching to the RBC intracellular level. The improved metabolic acidosis might occur as a result of the increase in RBC-2.3DPG during BF. This increase in RBC-2.3DPG has the effect of reducing the affinity of oxygen for hemoglobin and allows more oxygen to be delivered to the peripheral tissues although the increase in RBC-pH by dialysis restricts the dissociation of oxygen from hemoglobin.
2,3-Diphosphoglycerate↗
Combined effect of rebamipide and ecabet sodium on Helicobacter pylori adhesion to gastric epithelial cells.
Helicobacter pylori is a major etiological agent in gastroduodenal disorders. The adhesion of H. pylori to gastric epithelial cells is the initial step of H. pylori infection. Inhibition of H. pylori adhesion is thus a therapeutic target in the prevention of H. pylori infection. We have reported that rebamipide and ecabet sodium, mucoprotective antiulcer agents, independently inhibit H. pylori adhesion. However, the antiadhesion activity of each antiulcer agent was incomplete. Experiments were performed to evaluate the combined effect of rebamipide and ecabet sodium on H. pylori adhesion to gastric epithelial cells. MKN-28 and MKN-45 cells, derived from human gastric carcinomas, were used as target cells. Twelve clinical isolates of H. pylori were used in this study. We evaluated the effects of rebamipide and ecabet sodium, individually and in combination, on H. pylori adhesion to target cells quantitatively using our previously established enzyme-linked immunosorbent assay. Rebamipide and ecabet sodium each partially inhibited H. pylori adhesion. In contrast, adhesion was almost completely inhibited by pretreating target cells and H. pylori with the combination of rebamipide and ecabet sodium. Our studies suggest that the synergistic antiadhesion activity of rebamipide and ecabet sodium is greater than that of each antiulcer agent alone.
Abietanes↗
Screening of BRCA1 mutation using immunohistochemical staining with C-terminal and N-terminal antibodies in familial ovarian cancers.
We examined the subcellular localization of BRCA1 proteins using immunohistochemical staining with C-terminal (GLK-2 antibody) and N-terminal (Ab-2 antibody) monoclonal antibodies in 44 familial ovarian cancers. Among these, 24 cases were associated with 13 independent germ-line mutations of BRCA1, and loss of heterozygosity (LOH) at one or more BRCA1 microsatellite markers was found in all 21 informative tumors tested. With GLK-2 antibody, cytoplasmic staining was observed in 15 of 16 tumors (93.8%) with mutation in exon 11, and BRCA1 staining was absent in 8 of 8 tumors (100%) with mutation in exons other than exon 11. When immunohistochemical staining was performed with Ab-2 antibody, both nuclear and cytoplasmic staining were observed in 14 of 16 tumors (87.5%) with mutation in exon 11. Interestingly, nuclear staining was observed in 3 of 3 tumors (100%) with mutation downstream of exon 11, even though no staining was detected in 5 of 5 tumors (100%) with mutation upstream of exon 11. On the other hand, in familial ovarian cancers without BRCA1 mutations, nuclear staining or both nuclear and cytoplasmic staining was observed in 18 of 20 specimens (90%) and 20 of 20 specimens (100%) with GLK-2 antibody and with Ab-2 antibody, respectively. These results suggest that an immunohistochemical assay in combination with employing the C-terminal and the N-terminal antibodies appears to have potential as a reliable and useful technique for the screening of BRCA1 mutations, at least to predict the status of mutation, upstream or downstream of exon 11.
BRCA1 Protein↗
[Sensitivity and specificity of rapid diagnosis kit detecting separately influenza A and B viruses].
Sensitivity and specificity of the Directigen Flu A + B kit, a rapid test for influenza virus A and B, were evaluated. This test detects influenza A and B viruses separately by EIA. Reactivity of the kit was tested using a total of 23 isolates: 13 isolates of human influenza virus A (H1N1, H3N2) and 10 isolates of human influenza virus B. All of the isolates were tested positive and no difference in reactivity was found in antigenic variables and subtypes. The kit was only reactive to influenza virus A and B, not reactive to other viruses. Typical influenza A and B strains were tested for detection limit. 7.8 x 10(3) pfu/ml was a detection limit for influenza virus A (H1N1: Beijing/262/95), 4.7 x 10(4) pfu/ml for influenza virus A (H3N2: Kitakyusyu/159/93), and 3.1 x 10(4) pfu/ml for influenza virus B (Guangdong/05/94). The Directigen Flu A + B kit was a easy-to-use, rapid detection device and the kit has sensitivity and specificity equivalent to other diagnostic devices, suggesting the kit are useful in medical institutions.
Evaluation Studies as Topic↗
[Evaluation of the rapid detection test for influenza A and B viruses using neuraminidase activity].
The ZstatFlu test (ZymeTx, USA) is a rapid detection kit for influenza A and B viruses. This test is based upon the reaction between viral neuraminidase from influenza viruses and a chromogenic substrate. The clinical performance of the ZstatFlu test was determined by comparison with viral isolation in cell culture. A total of 176 respiratory specimens from 172 pediatric patients with influenza like illnesses during the 1998/99 season were tested. Influenza viruses were recovered from 97 specimens (type A: 6, type B: 91) in cell culture. ZstatFlu demonstrated 67.4% sensitivity (29/43) and 62.7% specificity (37/59) for throat swabs. Of the 22 ZstatFlu-positive, culture-negative throat swabs tested by RT-PCR, 18 were positive by RT-PCR. ZstatFlu showed 48.1% sensitivity (26/54) and 90.0% specificity (18/20) for nasopharyngeal aspirates. Of the two ZstatFlu-positive, culture-negative nasopharyngeal aspirates tested by HI titer of paired sera, one showed a 4-fold increase of HI titer. Nasopharyngeal aspirates therefore showed lower sensitivity than throat swabs at this test, different from EIA test kits such as Directigen FluA or FLU OIA. Overall, only 5 specimens were false positive by the ZstatFlu test. Therefore, this test demonstrated high specificity and positive predictive value. In conclusion, the ZstatFlu test is useful for the rapid detection of influenza A and B viruses to identify patients who need antiviral treatment.
Adolescent↗
Antibody to heat shock protein can be used for early serological monitoring of Helicobacter pylori eradication treatment.
Infection with Helicobacter pylori induces humoral immune responses against various antigens of the bacterium. Heat shock proteins (hsps) are immunodominant antigens in various diseases including H. pylori infection. In the present study, we measured the anti-hsp antibody titers in 42 patients with H. pylori-infected peptic ulcers during a bacterial eradication study. The patients were treated with a proton pump inhibitor and antimicrobial agents to eradicate the organism. Their sera were obtained at pretreatment and at 1 month and 6 months after the eradication therapy. The titers of immunoglobulin G antibodies to the H. pylori hsp, whole-cell lysate, and urease (30-kDa subunit) antigens in serum were measured by a capture enzyme-linked immunosorbent assay. The levels of H. pylori hsp60 antibodies in sera collected 1 month after treatment had declined significantly, even when changes in the titers of antibodies to whole-cell and urease antigens were not apparent. These results suggest that measurement of antibodies to H. pylori hsp60 in serum is useful for the early monitoring of the effectiveness of eradication therapy.
Adult↗