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Biomedical subjects

M Inoue

Publications and source records attributed to M Inoue.

At least 199 records · Page 11Linked to original sources

Regulation of aromatase activity in bone-derived cells: possible role of mitogen-activated protein kinase.

Fetal human osteoblast-like cells and the THP-1 cell line that differentiates into macrophage/osteoblast-like cells in the presence of Vitamin D3 and which possesses high aromatase activity, constitute a useful model with which to study the regulation of aromatase in bone. We showed that dexamethasone (DEX)-induced aromatase activity in the THP-1 cell line is completely suppressed by forskolin and by dibutyryl cAMP. We therefore investigated the contribution of mitogen-activated protein kinase (MAPK) to the regulation of aromatase, because cAMP inhibits MAPK in many cells. We examined the role of MAPK on aromatase activity using PD98059, a selective inhibitor of MEK-1. PD98059 (100 microM) reduced DEX+interleukin (IL)-1beta-induced aromatase activity in human osteoblast-like cells by more than 90%, whereas 50% of the aromatase mRNA concentration was retained compared with the control incubated with DEX+IL-1beta. PD98059 (50 microM) reduced the activity of aromatase in THP-1 cells by 80% without significantly affecting the mRNA level. These results indicated that MAPK plays an important role in aromatase activation at the post-transcriptional level.

1-Methyl-3-isobutylxanthine↗

Bile acid reflux and possible inhibition of Helicobacter pylori infection in subjects without gastric surgery.

Bile acids are generally known to inhibit growth of Helicobacter pylori in vitro, but whether they do so in humans with no gastric surgery has been uncertain. The present study addresses this issue. Among healthy control subjects with preserved acid secretion, H. pylori-positive subjects were older and had lower gastric bile acid concentrations than H. pylori-negative subjects (P < 0.05). Among gastric ulcer patients with preserved acid secretion, H. pylori-positive patients had a higher basal acid output than H. pylori-negative patients (P < 0.05). Among H. pylori-positive subjects with preserved acid secretion, duodenal ulcer patients had a higher basal and maximum acid output than healthy control subjects (P < 0.01). In conclusion, gastric bile acids may suppress initial stages of H. pylori infection in subjects without gastric surgery. However gastric bile acids may have little effect on peptic ulcer disease, once H. pylori infection is established.

Adolescent↗

Association of family history and other risk factors with breast cancer risk among Japanese premenopausal and postmenopausal women.

OBJECTIVES: To determine the impact of family history (FH) on anthropometric and reproductive risk factors for breast cancer, a case-referent study was conducted using data from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC), Japan. METHODS: In total, 1584 breast cancer cases were included and 15,331 women, confirmed as free of cancer, were recruited as the referents. Odds ratios and 95% confidence intervals were determined by logistic regression analysis. Separate analyses were performed for premenopausal and postmenopausal women. RESULTS: Height, weight, and current body mass index (BMI) were positively associated with postmenopausal breast cancer regardless of FH, while these anthropometric factors did not alter risk in premenopausal women. The impacts of height and weight on postmenopausal breast cancer were more pronounced among FH women. There was little association with reproductive risk factors for premenopausal or postmenopausal breast cancer in FH cases, in clear contrast to the non-FH cases. CONCLUSIONS: These findings suggest some differences in risk impact of common etiologic factors between familial breast cancer and sporadic cases that may give pointers to further analysis of host-specific factors. They imply that avoidance of obesity after menopause may reduce the risk of breast cancer, regardless of FH.

Adult↗

Periodontal status and serum antibody titers for Porphyromonas gingivalis fimbriae in a rural population in Japan.

BACKGROUND, AIMS: The present study was undertaken to assess the periodontal status of a rural Japanese population and to study the correlation between the periodontal status and the serum antibody titers for Porphyromonas gingivalis (Pg) fimbriae. METHOD: A total of 236 individuals were examined for their periodontal conditions by the use of the community periodontal index for treatment needs (CPITN), and serum antibody titers for Pg fimbriae in their peripheral blood samples were evaluated using the enzyme-linked immunosorbent assay. RESULTS: There was a substantially larger proportion of edentulous subjects in the age group older than 60 years. The remaining teeth were 24.1, 23.2, 11.1 and 10.1 per person in the 40-49, 50-59, 60-69 and > or = 70 age groups, respectively. The % of sextants with a CPITN code of missing sextant (MS) increased towards elderly and reached >60% in the age group of > or = 70 years, as the % of the CPITN 2, 1 or 0 sextant decreased. The % of CPITN 4 and 3 sextants did not differ between different age groups and were about 6-8% and 15-20%, respectively. The % of CPITN 1 or 0 sextants was higher in female subjects than in male subjects in the 60-69 and > or = 70 age groups, while the % of CPITN 4 or 3 sextants was higher in male subjects than in female subjects in all age groups. There was no significant difference between various age groups in the mean serum antibody titers for Pg fimbriae. The mean anti-Pg fimbriae antibody titers was significantly higher for the subjects with a maximum CPITN code 4 (max.-CPITN 4 subject) than for the subjects with lower maximum CPITN codes. The antibody titers varied extensively among the max.-CPITN 4 or 3 subjects, but not among the max.-CPITN 2/1/0 or MS subjects. CONCLUSIONS: The present study demonstrated that tooth loss is a remarkable event in elderly subjects and that oral prophylaxis and mechanical debridement should be mandatory in the population examined. It was also demonstrated that the serum antibody titers against Pg fimbriae could be useful for screening individuals with moderate to severe periodontitis.

Adult↗

Prognostic significance of p27 and Ki-67 expression in mucoepidermoid carcinoma of the intraoral minor salivary gland.

p27 and Ki-67, a universal cyclin-dependent kinase inhibitor and a proliferative cell marker, respectively, have been useful in predicting clinical aggressiveness in various human tumors. We studied clinicopathologic significance of these molecules in mucoepidermoid carcinoma of the intraoral minor salivary gland. Expression of p27 and Ki-67 was assessed immunohistochemically in primary mucoepidermoid carcinomas from 31 patients without distant metastasis at surgery. Correlation each of p27 and Ki-67 expression was analyzed with various clinicopathologic parameters including age, sex, primary tumor site, tumor size, nodal metastasis, clinical stage, and histologic grade. The latter was evaluated using a point-scoring scheme of Auclair et al. that consists of five histologic factors (intracystic component, neural invasion, necrosis, mitosis, and anaplasia). p27 expression was correlated inversely with histologic grade (P =.007), but with none of other factors. When the correlation of p27 expression was further examined with each of the histologic factors, it was correlated significantly with intracystic component, but not with neural invasion, necrosis, mitosis, or anaplasia. Ki-67 expression was correlated significantly with histologic grade only in the clinicopathologic factors (P <.0001), and in the histologic factors, with necrosis, mitosis, and anaplasia. Multivariate prognostic analyses were performed to identify independent risk factors for both disease-free and overall survivals. Large tumor size (P =.031, relative risk = 5.5) and low p27 expression (P =.012, relative risk = 5.2) were risk factors for worse disease-free survival. Low p27 expression (P =.015, relative risk = 15.2) was selected as a risk factor for worse overall survival. Other factors including age, sex, tumor site, nodal status, clinical stage, histologic grade, and Ki-67 did not emerge as independent risk factors in either prognostic analysis. These data suggest that p27 may be useful in estimating prognosis of the patients who have mucoepidermoid carcinoma of the intraoral minor salivary gland.

Adolescent↗

Kinetics of plasma cytokines after hematopoietic stem cell transplantation from unrelated donors: the ratio of plasma IL-10/sTNFR level as a potential prognostic marker in severe acute graft-versus-host disease.

The plasma levels of a panel of cytokines and cytokine-associated molecules (IL-1alpha, IL-2, IL-4, IL-6, IL-10, IL-12, IL-15, macrophage colony-stimulating factor (M-CSF), interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), soluble IL-2 receptor (sIL-2R), soluble tumor necrosis factor receptor I or II (sTNFRI or II)) were assessed in 56 plasma samples of 13 pediatric patients undergoing hematopoietic stem cell transplantation (HSCT, bone marrow in 12 and cord blood in one) from unrelated donors. Eight patients developed severe (grade III-IV) acute GVHD (aGVHD). The plasma IL-6, IL-10, M-CSF, sTNFRI and II levels were significantly high in the severe aGVHD group compared to the mild aGVHD group (grade 0-II). The plasma IL-15 level increased transiently in the early period following HSCT and remained high in the severe aGVHD group even after 4 weeks following HSCT. Based on analysis of the correlations between the kinetics of the plasma cytokine levels after HSCT and the clinical manifestations of aGVHD, IL-15 and/or M-CSF were involved in the development of aGVHD, following elevation of the plasma IL-10 and sTNFRI or II levels. These kinetics suggest that IL-10 and sTNFRs worked as suppressor cytokines and seemed to suppress clinical manifestations of aGVHD. Furthermore, it seemed that the plasma ratio of IL-10/sTNFRII from 5 to 12 weeks following HSCT was linked to the poor outcome in the patients with severe aGVHD, suggesting that IL-10 plays an important role in protecting hosts from transplantation-related complications, including GVHD.

Acute Disease↗

Skeletal muscle regeneration after insulin-like growth factor I gene transfer by recombinant Sendai virus vector.

We scrutinized the applicability and efficacy of Sendai virus (SeV) vectors expressing either LacZ or human insulin-like growth factor-I (hIGF-I) in gene transfer into skeletal muscle. Seven days after the intramuscular injection of LacZ/SeV X-gal labeled myofibers were demonstrated in rat anterior tibialis muscle with/without bupivacaine treatment and the transgene expression persisted up to 1 month after injection. Recombinant hIGF-I was detected as a major protein species in culture supernatants of a neonatal rat myoblast cell line L6 and thus induced the cells to undergo myogenetic differentiation. The introduction of hIGF-I/SeV into the muscle showed a significant increase in regenerating and split myofibers which were indicative of hypertrophy, and also an increase in the total number of myofibers, in comparison to that seen in the LacZ/SeV-treated control muscle. These results demonstrate that SeV achieves high-level transgene expression in skeletal muscle, and that hIGF-I gene transfer using SeV vector may therefore have great potential in the treatment of neuromuscular disorders.

Animals↗

Dendritic attenuation of synaptic potentials in the CA1 region of rat hippocampal slices detected with an optical method.

We directly measured fast excitatory postsynaptic potentials (EPSPs) along the dendrites of hippocampal CA1 pyramidal neurons by employing an optical method to study how synaptic potentials spread along the dendrites. Rat hippocampal slices were stained with a fluorescent voltage-sensitive dye JPW1114 and optical signals were monitored with a 16 x 16 photodiode array system. A stimulating electrode was placed either at stratum lacunosum moleculare to activate perforant fibers that make synaptic contacts to the distal apical dendrites or at stratum oriens to induce EPSPs at the basal dendrites of CA1 pyramidal cells. CNQX-sensitive components of the optical signals, which were assumed to be population EPSPs, were isolated. Propagation and attenuation of the CNQX components were successfully observed with the optical method. At the cell body layer, the peak of the CNQX-sensitive component was delayed by 17.08 +/- 1.64 ms from the input sites. Additionally we performed a simulation study to estimate the passive membrane parameters of the apical dendrites. Estimated apparent specific internal axial resistance (Ri) following stratum lacunosum moleculare stimulation was 76.0 +/- 4.2 Omega.cm and apparent specific membrane resistance (Rm) was 27.8 +/- 2.1 kOmega.cm2 (assuming the specific membrane capacitance of dendrites Cm = 1.6 microF/cm2). These values are comparable to those previously reported. When synaptic inputs were applied at stratum oriens, these apparent passive membrane parameters were different (high Ri and low Rm), suggesting that nonuniform dendritic membrane conductance or voltage-dependent conductances which are active near the resting potential may contribute to the measured passive membrane properties.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Involvement of Fc gamma receptor polymorphism in the therapeutic response of idiopathic thrombocytopenic purpura.

Clearance of autoantibody-sensitized platelets through Fc gamma receptors on phagocytic cells is one of the main mechanisms of thrombocytopenia in idiopathic thrombocytopenic purpura (ITP). We examined the Fc gamma RIIA-131R/H and Fc gamma RIIIA-158V/F polymorphisms in 104 adult chronic ITP patients, and in 59 healthy control subjects using polymerase chain reaction-based allele-specific restriction analysis. The frequency of Fc gamma RIIA genotypes (131H/H, H/R, R/R) was not significantly different between patients and controls, and did not correlate with the responsiveness to treatment. In contrast, among Fc gamma RIIIA genotypes, frequency of 158F/F homotype was smaller in ITP (P < 0.05). Furthermore, in Fc gamma RIIIA-158V/V homotype, the complete remission (CR) rate with medication (treatment with corticosteroid or other immunosuppressive agents) was significantly higher (60%) than that in 158V/F (10%) or 158V/F plus 158F/F, (P < 0.01, P < 0.05). Conversely, the CR rate after splenectomy in 158F/F and 158V/F types (64.3% and 54.6%) was higher than in 158V/V (25%). Our results indicate that the polymorphism of Fc gamma RIIIA, but not Fc gamma RIIA, influences the response to treatment in ITP.

Adult↗

An ultrasensitive assay revealed age-related changes in serum oestradiol at low concentrations in both sexes from infancy to puberty.

OBJECTIVE: Intensive studies of oestrogen receptors have suggested extragonadal functions of oestrogen. However, the in vivo extragonadal functions of oestradiol remain unclear because of the lack of an adequate assay system at low concentrations. In this study, we assessed the usefulness of a new ultra-sensitive assay for children. METHODS: Serum oestradiol was measured with an ultrasensitive assay (assayable concentration: 5-1,835 pmol/l: ESTR-US-CT, CIS biointernational, France). Intra- and interassay coefficients of variation at low concentrations (< 36.7 pmol/l) were 8.2 +/- 6.8 (0.1-31.2)% and 8.3 +/- 3.7 (7.5-12.9)%, respectively. SUBJECTS: Sera from 88 healthy children (55 males and 33 females; 1 month to 16 years old) and 31 patients who underwent gonadal suppression therapy were analysed. RESULTS: Age-related changes were observed in both sexes. Serum oestradiol concentrations in childhood decreased slightly compared to those in infancy, then increased at puberty. Most prepubertal children showed oestradiol concentrations lower than 36.7 pmol/l. A study on patients who underwent gonadal suppression therapy revealed oestradiol changes within low concentrations, depending on the stage of the therapy. CONCLUSIONS: The new assay was considered precise enough for the assessment of oestradiol secretion at low concentrations in childhood. Age-related changes in serum oestradiol suggested gonadal activity in the prepubertal period. This assay could be a powerful tool for investigating novel oestradiol functions in vivo.

Adolescent↗

Reliability and validity of Kasahara's scale of melancholic type of personality (Typus melancholicus) in a German sample population.

We explored the reliability and validity of Kasahara's scale of melancholic type of personality (KMT) in a German sample population. Subjects comprised 66 patients diagnosed with an affective disorder (F3, ICD-10) and 94 controls. Concerning reliability, KMT scores showed internal consistency with Cronbach's alpha coefficients of 0.65 for patients and 0.67 for controls. The KMT items, except for number 13 in controls, showed significant item-total correlations. In a test-retest procedure, the KMT total score and individual item scores were statistically similar and correlated. These results indicate reliability of the KMT. Concerning validity, KMT scores were significantly higher in patients than in controls. By controlling the effects of age and sex, partial correlation coefficients in a comparison of KMT and Zerssen's F-List (F-List) scores were 0.40 in patients and 0.53 in controls. These results show both the constructive and concurrent validity of the KMT. Sufficient reliability and validity of the KMT were shown in this German sample population to encourage cross-cultural investigation of Typus melancholicus.

Adult↗

Growth and endocrine function during school age in very low-birth weight infants.

BACKGROUND: Short stature and low bodyweight are commonly encountered problems in the clinical follow up of premature infants. However, details about the underlying pathophysiology are unknown in these cases. METHODS: Evaluations of growth and endocrine function were performed in 23 very low-birth weight (VLBW) infants between 11.3 and 14.3 years of age. RESULTS: The mean (+/-SD) scores for height and weight were -0.50+/-0.97 and -0.50+/-1.10 SD, respectively. Mean serum insulin-like growth factor (IGF)-I and urine growth hormone (GH) levels were 402+/-138 ng/mL and 18.0+/-17.5 pg/mg creatinine, respectively. Serum IGF-I and urine GH levels were within the normal range for all patients. The bone age values were consistent with the patient's true age. Physical signs of puberty were detected in 15 of 23 patients (65%). Using bone ages to predict final adult height yielded a score of -0.52+/-1.08 SD. CONCLUSIONS: Despite the almost normal results of serum IGF-I, urine GH levels and bone age, the physical growth of these VLBW infants was less than that of normal birth weight children, as was their predicted adult growth.

Adolescent↗

Lymph node metastasis along the recurrent nerve chain is an indication for cervical lymph node dissection in thoracic esophageal cancer.

This study examined whether recurrent nerve chain node metastasis serves as an indicative factor for cervical lymph node dissection in thoracic esophageal cancer. The association of recurrent nerve chain lymph node metastasis and cervical node metastasis was analyzed for 91 patients with thoracic esophageal cancer who had undergone three-field lymph node dissection. In patients with upper thoracic esophageal cancer, the incidence of cervical lymph node metastasis was similar regardless of recurrent nerve chain node metastasis. On the other hand, in patients with middle or lower esophageal cancer, the incidence was significantly higher in recurrent nerve-positive (16/31, 51.6%) than in recurrent nerve-negative (5/43, 11.6%) patients. The prognosis of patients with recurrent nerve chain node metastasis was significantly better in the three-field dissection group than in the two-field dissection group, while in patients with no recurrent nerve chain node metastasis, survival was similar between the two groups. In conclusion, cervical lymphadenectomy can be omitted for recurrent nerve chain node-negative patients with middle and lower thoracic esophageal cancer.

Abdomen↗

Red blood cell status in alcoholic and non-alcoholic liver disease.

Macrocytosis is most commonly associated with vitamin B(12) and folic acid deficiency, followed by alcoholism, liver disease, and other pathologic conditions. We studied the red cell and vitamin status in 423 consecutive patients with various liver diseases, including 31 with acute viral hepatitis (AVH), 105 with chronic hepatitis (CH), and 134 with alcoholic liver disease (ALD), who consisted of 84 with non-cirrhotic alcoholic liver disease (NCALD) and 50 with alcoholic liver cirrhosis (ALC), 60 with non-alcoholic liver cirrhosis (NALC), and 93 with hepatocellular carcinoma (HCC). The mean corpuscular volume (MCV) and red cell distribution width (RDW) were significantly higher in patients with ALD and NALC, and among them macrocytosis occurred more frequently in patients with ALC. Macrocytic anemia was mostly found in cirrhotic patients, in which the Child-Pugh score was closely related to the development of macrocytic anemia. In ALD, the MCV was significantly correlated with the estimated alcohol consumption and inversely correlated with the serum folic acid level, which, however, was often maintained within the normal range in patients with macrocytic ALC. After abstinence from alcohol, the MCV and RDW were reduced significantly and were associated with an increasing serum folic acid level. This suggests that macrocytic anemia was a common feature of alcoholic and non-alcoholic liver cirrhosis and that alcohol abuse and folic acid deficiency play a secondary role in macrocytosis.

Adult↗

Parental enforcement of bedtime during childhood modulates preference of Japanese junior high school students for eveningness chronotype.

We examined the effect of home bedtime discipline during childhood on morningness and eveningness (M-E) preference by Japanese junior high school students. M-E was assessed by the M-E Questionnaire (MEQ) of Torsvall and Akerstedt (the higher the score, the greater the preference for morningness), and parental determination of bedtime during childhood was ascertained using an original questionnaire. The average M-E score of adolescents living in urban Kochi City (mean +/- SD; 15.10 +/- 3.42) was significantly lower (P < .01) than the score of those in suburban districts (16.14 +/- 3.44). Overall, 43.1% of the junior high school students in Kochi City compared to 53.0% of the students living in suburban districts had their bedtime decided during childhood by parents (P < .01). In Kochi City, the M-E score for boys (14.62 +/- 3.51) was lower (P < .01) than girls (15.53 +/- 3.28). During childhood, parents decided the bedtime for 49% of the girls compared to 36.6% of the boys (P < .01). Boys whose bedtime was not decided by parents during childhood had a somewhat stronger preference for eveningness (14.20 +/- 3.53) (P < .05) compared to those whose bedtime was decided by parents (15.12 +/- 3.36). The results suggest bedtime discipline at home during childhood has an effect on adolescent chronotype, modulating the extent of shift to evening ness in Japanese junior high school boys in particular.

Adolescent↗

Gene-environment interaction between an aldehyde dehydrogenase-2 (ALDH2) polymorphism and alcohol consumption for the risk of esophageal cancer.

Aldehyde dehydrogenase-2 (ALDH2) degrades acetaldehyde metabolized from ethanol. Its encoding gene ALDH2 has a functional polymorphism: ALDH2 Glu487LYS: An association between this polymorphism and esophageal cancer among alcoholics has been reported. To further evaluate the gene-environment interaction, a hospital-based case-control study was conducted. Cases were 102 patients with histologically confirmed esophageal cancer and controls were 241 non-cancer outpatients of Aichi Cancer Center. ALDH2 genotypes were examined by a PCR-CTPP method developed in our laboratory, which does not require a digestion stage. Logistic regression analysis was employed for estimation of relative risk and gene-environment interaction. The allele frequency for ALDH2 Lys487 was 0.28, consistent with previous reports. The age, sex, smoking and drinking status adjusted odds ratio for the ALDH2 Glu/Lys and Lys/Lys genotypes as compared with the Glu/Glu genotype was 3.43 (95% CI 1.74-6.75). The odds ratio for heavy drinking was 49.6 (14.5-169.4) among Lys487 carriers and 7.84 (2.77-22.2) for the Glu/Glu genotype. The gene-environment interaction between alcohol drinking and the ALDH2 Lys487 allele was 6.84 (2.39-19.6), whereas no significant interaction was obtained with smoking status. Although limited because of its prevalent case-control design, our study revealed a strong gene-environment interaction between ALDH2 polymorphism and heavy alcohol consumption. Taking the observed high risk of esophageal cancer in association with the ALDH2 Lys487 allele into consideration, reducing alcohol intake may be most protective among Lys487 allele carriers of this polymorphism.

Adult↗