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Biomedical subjects

K Miwa

Publications and source records attributed to K Miwa.

At least 199 records · Page 11Linked to original sources
PubMed1996

[Prevalence of depressive symptoms and its relation to demographic variables in high school students].

In order to determine the prevalence of depressive symptoms and to examine its relationship to demographic variables in late adolescents, questionnaires were administered on 3,254 high school students in Okinawa. Depressive symptoms were assessed using the Zung Self-rating Depression Scale (SDS). The results were as follows: The SDS score distribution curve was near-normal. The mean SDS scores of males and females were 40.4 and 41.7, respectively. Overall, 53.4% of males and 61.4% of females had depressive symptomatology according to an SDS cut-off point of 40 or greater. There were significant differences in mean SDS scores and prevalence by gender. Females had higher depressive symptom scores. Both indicators of depressive symptomatology were higher than those in U.S. adolescents and Japanese adults. When controlling for the effect of school type, both male and female students living in urban ureas of the main island had more depressive symptoms than students living in rural areas of remote islands. When controlling for the effect of region, female students attending vocational high schools showed more depressive symptoms than other high school students. However, there was no difference by school type among male students. The high prevalence of depressive symptoms suggests that it is necessary to modify the assessment cut-off point for high school students and to promote further school mental health care.

Adolescent↗
PubMed1995

Retinoic acid enhances plasminogen activation on the cell surface.

The importance of cell-associated plasminogen activation in the extracellular matrix degradation processes is becoming increasingly evident. To elucidate the modulators of net plasminogen activation on the cell surface, we have recently established an assay system. Using this system, we examined the effects of several candidate modulators on cell surface plasminogen activator in the human fibrosarcoma cell line HT-1080 and the SV40-transformed human lung fibroblast cell line WI-38 VA 13 2RA. Although the majority of the candidates had no effect or a selective effect on either cell line, only retinoic acid markedly enhanced cell surface plasminogen activator activity in both HT-1080 and WI-38 VA13 2RA cells in a time-dependent manner. The effect of retinoic acid was neutralized by actinomycin D. The enhanced activity was inhibited by anti-uPA IgG and by pretreatment with phosphatidylinositol-specific phospholipase C. These findings suggest that retinoic acid increases the amount of receptor-bound uPA via de novo synthesis, and that it plays an important role in modulating cell-associated plasminogen activation.

Cell Line, Transformed↗
PubMed1995

Mobilization of gastric histamine during repeated administration of a proton potassium adenosine triphosphatase inhibitor in intact and antrectomized rats.

Intact and antrectomized female rats were treated with the potent proton pump inhibitor, E3810 (daily 40 mg/kg weight, s.c.) for 4 weeks. Plasma gastrin concentration and urinary excretion of N-terminal big gastrin increased until day 14 and persisted at a high level in intact rats treated with E3810, but did not increase in antrectomized rats. Urinary excretion of histamine increased progressively and reached 7 times the control value following 4 weeks of treatment with E3810 in intact rats, but not in antrectomized rats. At the termination of the treatment, the endocrine cell density in the oxyntic mucosa of intact rats had increased by 85% with increased histamine content and elevated histidine decarboxylase activity, while antrectomized rats showed a low histamine level and low histidine decarboxylase activity. Administration of gastrin-17 I (10 micrograms/kg weight, sc) itself caused a significant increase in urinary excretion of histamine, which was inhibited by the specific gastrin receptor antagonist, L-365,260. These results suggests that the massive urinary excretion of histamine caused by the treatment with E3810 reflects gastrin-induced mobilization of gastric histamine and that neither E3810 itself nor E3810-induced luminal pH elevation has direct effects on mobilization of oxyntic mucosal histamine.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1995

Fine tuning of peptide binding to HLA-B*3501 molecules by nonanchor residues.

The prerequisites of peptide HLA-B*3501 interactions have been revisited by quantitative peptide binding assays with 190 chemically synthesized peptide possessing two anchor residues corresponding to the HLA-B*3501 peptide motif and a statistical residue-position analysis of binding and nonbinding peptides. According to the peptide motif of HLA-B*3501, aliphatic hydrophobic (Leu, Ile, and Met) or aromatic residues (Tyr and Phe) specify the main anchor at the C terminus, and position 2 renders an auxiliary anchor for proline. The importance of these residues was confirmed as a minimum requirement for peptide binding. Moreover, we demonstrated that high affinity peptide binding requires more than one favorable position of positions 3, 4, and 7. Aliphatic hydrophobic residues and residues that contain -OH or -SH side chains in position 3, 7, and 4 significantly enhance binding. Positions 1 and 5, or 7 may deteriorate peptide binding if these positions are held by proline and small residues (Ala and Gly) or basic residues carrying positively charged side chains (Arg and Lys), respectively. Positions 6 and 8 were statistically free of constrains. Yet, bulky aromatic residues and basic residues with a positively charged side chain at position 8 decreased the binding affinity. These findings were used to assess the predictability of binding and nonbinding peptides. Our binding predictions of 28 nonamers were verified by experimental data. Taking into account the importance of anchor and nonanchor positions in peptide binding and their practical value in peptide binding prediction, the search for peptide epitopes becomes more efficient.

Amino Acid Sequence↗
PubMed1995

Duodenogastric reflux and foregut carcinogenesis.

Epidemiologic cohort studies have established that after distal gastric resection, there is a higher risk of gastric carcinoma. It is likely that a main factor of this higher risk is the excessive duodenogastric reflux induced by surgery, because the incidence of stump carcinomas is higher in Billroth II than in Billroth I, and most of the stump carcinomas are located near the stoma. In addition, several groups of investigators have suggested that duodenogastric reflux per se induces stump carcinomas in rats. There is another human duodenogastric reflux, the primary duodenogastric reflux, through the pylorus. Experiments in animals have demonstrated that this type of duodenal reflux also induces gastric carcinomas in the antrum of the stomach that has not undergone surgery. Recent clinical attention has focused on the role of duodenogastric reflux in the pathogenesis of Barrett's esophagus and subsequent esophageal adenocarcinomas. Experimentally, reflux of duodenal contents into the esophagus can cause not only Barrett's esophagus and subsequent adenocarcinomas, but also squamous cell carcinomas. These findings suggest that duodenogastric reflux may be implicated in gastric and esophageal, that is, foregut carcinogenesis.

Adenocarcinoma↗
PubMed1995

How MHC class II molecules reach the endocytic pathway.

We have examined trafficking of major histocompatibility complex (MHC) class II molecules in human B cells exposed to concanamycin B, a highly specific inhibitor of the vacuolar H(+)-ATPases required for acidification of the vacuolar system and for early to late endosomal transport. Neutralization of vacuolar compartments prevents breakdown of the invariant chain (Ii) and blocks conversion of MHC class II molecules to peptide-loaded, SDS-stable alpha beta dimers. Ii remains associated with alpha beta and this complex accumulates internally, as ascertained biochemically and by morphological methods. In concanamycin B-treated cells, a slow increase (> 20-fold) in surface expression of Ii, mostly complexed with alpha beta, is detected. This surface-disposed fraction of alpha beta Ii is nevertheless a minor population that reaches the cell surface directly, or is routed via early endosomes as intermediary stations. In inhibitor-treated cells, the bulk of newly synthesized alpha beta Ii is no longer accessible to fluid phase endocytic markers. It is concluded that the majority of alpha beta Ii is targeted directly from the trans-Golgi network to the compartment for peptide loading, bypassing the cell surface and early endosomes en route to the endocytic pathway.

Anti-Bacterial Agents↗
PubMed1995

High-density lipoprotein cholesterol level and smoking modify the prognosis of patients with coronary vasospasm.

A cardiovascular event analysis was performed in a subset of 80 consecutive patients with vasospastic coronary artery disease. During the follow-up period (30 +/- 2 months, mean +/- SD), 9 patients had vascular accidents, including acute myocardial infarction, unstable angina, and stroke (Group A), while the remaining 71 patients were eventfree (Group B). Serum total-cholesterol, low-density lipoprotein cholesterol, and triglyceride levels were not different between the two groups at the baseline as well as after follow-up. However, the HDL-C level at baseline was significantly lower in Group A (33.5 +/- 2.6 mg/dl) than in Group B (41.9 +/- 1.7 mg/dl, p < 0.05). The HDL-C level increased significantly during the follow-up in Group B (delta HDL-C: 6.2 +/- 1.2 mg/dl, p < 0.01), but not in Group A (delta HDL-C: -3.2 +/- 2.7 mg/dl). The HDL-C level after follow-up was significantly lower in Group A (30.3 +/- 2.9 mg/dl) than in Group B (48.1 +/- 1.5 mg/dl, p < 0.01). Current smokers at the end of the follow-up period were more prevalent in Group A (67%) than in Group B (11%, p < 0.01). Cardiovascular accidents occurred more often in current smokers (6/14, 43%) at the end of the follow-up than in current nonsmokers, including quitters (3/66, 5%; p < 0.05). The HDL-C level was increased significantly (delta HDL: 6.2 +/- 1.3 mg/dl, p < 0.01) in the latter patients, but not in the former (delta HDL: -0.4 +/- 2.9 mg/dl).(ABSTRACT TRUNCATED AT 250 WORDS)

Angina, Unstable↗
PubMed1995

Transcriptional repression of smooth-muscle alpha-actin gene associated with human papillomavirus type 16 E7 expression.

To explore the role of the E7 viral oncogene from human papillomavirus type 16 (HPV 16) in the regulation of cytoskeletal organization, we investigated alterations in particular cytoskeletal components in rat embryonal fibroblasts and three transformants of rat embryonal fibroblast cells produced by transfections with HPV16 E7 alone (TF1), HPV16 E7 plus adenovirus type 5 E1B (TF3), and HPV16 E7 plus activated Ha-ras (TF4). Marked reductions in smooth-muscle (SM) alpha-actin content and disrupted organization of stress fibers detected by anti-SM alpha-actin antibody were evident in all the transformants. These cytoskeletal manifestations were associated with a significant reduction in the mRNAs in these cells. Transcriptional repression by the E7 gene was observed after transient transfection of a chloramphenicol acetyltransferase reporter gene with SM alpha-actin gene promoter. Nucleotides -123 to -39 of the SM alpha-actin gene promoter were required for the HPV16 E7 transcriptional repression as shown by the chloramphenicol acetyltransferase assay. The downregulation of this actin isoform mediated by the E7 oncoprotein may play an important role in cell transformation by HPV16.

3T3 Cells↗
PubMed1995

Susceptibility of plasma low density lipoprotein to cupric ion-induced peroxidation in patients with variant angina.

OBJECTIVES: The purpose of this study was to investigate the peroxidative susceptibility of plasma low density lipoprotein in patients with active variant angina and to compare it with that in subjects without coronary spasm. BACKGROUND: Oxidized or modified low density lipoprotein can impair endothelium-dependent vasoregulation and has atherogenic properties; it may be related to the genesis of coronary artery spasm by potentiating agonist-induced vasoconstriction. METHODS: The sensitivity of plasma low density lipoprotein for cupric ion (Cu2+)-induced peroxidation was examined. Low density lipoprotein was isolated from plasma in 112 patients: 21 with active variant angina, 18 with inactive variant angina without anginal attacks during the preceding 6 months, 39 with significant organic coronary artery stenoses but without rest angina and 34 control subjects without coronary artery disease. Lipid peroxidation products in low density lipoprotein were assayed as thiobarbituric acid-reactive substances before and after incubation with various concentrations of Cu2+ at 37 degrees C for 24 h. RESULTS: Significantly higher levels of generation of thiobarbituric acid-reactive substances from plasma low density lipoprotein after incubation with Cu2+ were seen in patients with active variant angina than in patients in the other three groups. The dose-response curve of low density lipoprotein peroxidation induced by Cu2+ shifted to the left in this group as compared with the curve in the other three groups. The vitamin E (alphatocopherol) content of low density lipoprotein fraction in these patients was significantly lower than that in the other groups. After > or = 6 months of an angina-free period in five patients with active variant angina, thiobarbituric acid-reactive substances induced by 0.5 mumol/liter Cu2+ in low density lipoprotein were significantly decreased and vitamin E content was significantly increased. CONCLUSIONS: These results indicate that vitamin E-deficient plasma low density lipoprotein in patients with active variant angina is highly susceptible to peroxidative modification.

Analysis of Variance↗
PubMed1995

The role of p53 inactivation in human cervical cell carcinoma development.

We investigated the association between human papillomavirus (HPV) infection and p53 gene mutation in 47 primary uterine cervical cancers. HPV DNA sequences were present in 43 cancers (91.5%), and one of these cancers contained a p53 gene mutation. In addition, one of the remaining four HPV-negative cancers also contained a p53 gene mutation. As a result, p53 inactivation corresponded to the development of 44 of the primary uterine cervical cancers studied (93.6%). We obtained both primary and recurrent tumours from four cases. In two of these cases, the HPV genomes that were present in an episomal state in the primary tumours were observed to have disappeared in the recurrent tumours. One of these recurrent tumours also contained a p53 gene mutation, which suggested the possibility that p53 inactivation was required in order to maintain the aggressive behaviour in this cancer either by an HPV infection or by a p53 gene mutation. No MDM2 gene amplification was observed in the tumours that carried neither HPV DNAs nor p53 gene mutations.

Adenocarcinoma↗
PubMed1995

Rationale for extensive lymphadenectomy in early gastric carcinoma.

The incidence of nodal metastasis in early gastric carcinoma (EGC) is 10-20%. However, the optimal nodal dissection for early gastric carcinoma has not been established. A retrospective study was conducted in 392 consecutive patients who underwent potentially curative distal gastrectomy for EGC between 1962 and 1990. Of these 295 patients treated after September 1972 were prospectively entered into an extensive lymphadenectomy protocol. These patients were compared with 97 patients with simple gastrectomy in respect of the causes of death after surgery and the 10 year disease-specific survival rate. The incidence of nodal metastasis in early gastric carcinoma patients was 13.0%. Operative mortality from extensive lymphadenectomy was almost the same as from simple gastrectomy (2.0% and 2.1% respectively). Extensive lymphadenectomy provided a significantly higher 10 year survival rate than limited lymph node dissection (97.9% vs 88.1% respectively; P < 0.005). Among patients with nodal metastasis, the survival rate following extensive lymphadenectomy was significantly higher than that after simple gastrectomy (87.5% vs 55.6%; P = 0.018). Among patients without nodal metastasis, there was no difference between the two groups in the survival rate (99.4% and 96.7% respectively; P = 0.12). Multivariate analysis using the Cox proportional hazards model disclosed two significant independent prognostic factors on disease-specific survival, the nodal involvement (risk ratio: 8.4; P < 0.0001) and the extent of lymph node dissection (risk ratio: 5.8; P < 0.005). Extensive nodel dissection appears to prevent recurrence and to improve the cancer-specific survival in EGC patients with nodal metastasis.

Adult↗
PubMed1995

The absence of evidence of staphylococcal toxin involvement in the pathogenesis of Kawasaki disease.

To detect a causative superantigen and to clarify a possible role for staphylococci in Kawasaki disease (KD), culture supernatants of individual bacterial isolates from 11 acute-stage patients were studied. Toxic shock syndrome toxin-1 (TSST-1) and antibody to TSST-1 and enterotoxins A (SEA), B (SEB), and C (SEC) in acute (mean, day 7) and late convalescent (mean, month 15) sera from 26 patients (12 with coronary artery aneurysms) and 22 age-matched controls were measured. Only 1 of 60 supernatants was mitogenic for human lymphocytes; it was 1 of the 4 Staphylococcus aureus isolates. Mitogenicity was neutralized by sera obtained after administration of intravenous gamma globulin (mean, week 4) but not by late convalescent sera. TSST-1 was detectable in 2 of 26 acute sera and 1 of 22 control sera. No KD but 1 control serum had IgM to TSST-1. IgG seroconversion rates to TSST-1, SEA, SEB, and SEC were 10%, 15%, 21% and 16%, respectively. These data do not support the involvement of toxin-producing staphylococci in KD.

Antibodies, Bacterial↗
PubMed1995

Effective and safe dose of intracoronary nicorandil in man.

Nicorandil is a hybrid of a nitrate and a potassium channel opener, and has a potent vasodilatory effect on coronary arteries. The effects of intracoronary injection of nicorandil on coronary circulation were examined in 12 adult patients with angiographically normal or near-normal left coronary arteries to determine the optimal dose of this agent. The intracoronary injection of nicorandil (up to 1 mg over 1 min) dilated left coronary artery segments in a dose-dependent manner, with no significant effects on systemic hemodynamic parameters. The percent increase in the epicardial coronary artery diameter with 1 mg nicorandil (31 +/- 5%, mean +/- SEM) was not significantly different from that with 0.3 mg sublingual nitroglycerin (39 +/- 5%). Coronary sinus venous oxygen saturation increased immediately after the intracoronary injection of 1 mg nicorandil, and then returned to the baseline level within 3 min. Neither arrhythmias nor conduction disturbances were observed. These results indicate that dilatation of the epicardial coronary artery was achieved with intracoronary nicorandil in a dose-dependent manner (up to 1 mg over 1 min) without any adverse effects in man, and the dilatory effect on coronary resistance vessels was of short duration.

Aged↗
PubMed1995

Culture conditions for improvement of L-threonine production using a genetically self-cloned L-threonine hyperproducing strain of Escherichia coli K-12.

We had constructed an L-threonine-hyperproducing strain of E. coli K-12 by recombinant DNA techniques. In this paper, culture conditions for the practical production of L-threonine were investigated using this strain. Cultivation temperature, concentration of required amino acids, and dissolved oxygen greatly influenced the yield of L-threonine. High production of L-threonine was obtained at a high level of dissolved oxygen for the recombinant strain, but not for the parent. This improved production was accompanied by a high copy number of recombinant plasmids and high activity of aspartokinase. Initial addition of L-threonine together with required amino acids greatly reduced the net production of L-threonine. To remove the reductive effect, methods for the addition of the required amino acids were tested. Lowering the required amino acids at a later stage of cultivation seemed to be effective to avoid the reductive effect of the accumulated L-threonine. By using the optimal conditions, the highest level of L-threonine production, 65 g/l, 48% yield, was achieved.

Amino Acids↗
PubMed1995

Expression of mRNA encoding the prostaglandin F2 alpha receptor in bovine corpora lutea throughout the oestrous cycle and pregnancy.

The abundance of mRNA encoding the PGF2 alpha receptor in bovine corpora lutea at different phases of the oestrous cycle and pregnancy was examined in relation to the number of [3H]PGF2 alpha binding sites. Corpora lutea were removed from cyclic (early: 3-5 days after ovulation; mid-cycle: 8-12 days after ovulation; late: 15-18 days after ovulation; and regressed: 20-21 days after ovulation) and pregnant (early: fetal size 9-13 cm (2-3 months); mid-cycle: fetal size 42-43 cm (5-6 months); and late: fetal size 78-80 cm (8 months)) cows and subjected to total RNA preparation, in situ hybridization and membrane preparation for [3H]PGF2 alpha binding assay. Northern blot analysis demonstrated that expression of PGF2 alpha receptor mRNA progressively increased from the early phase to the late phase of the oestrous cycle, and was markedly reduced at the regressed phase; while constant amounts of mRNA were observed in early and middle pregnant corpora lutea, and there was a significant reduction at late pregnancy. Specific high affinity [3H]PGF2 alpha binding sites with Kd values of 18.3-31.1 nmol-1 were observed in the luteal membrane during the oestrous cycle and pregnancy; this is consistent with the expression of PGF2 alpha receptor mRNA. The number of receptors decreased at the regressed phase and in early pregnancy. These results strongly suggest that PGF2 alpha is involved in not only luteolysis but also luteal functions in both pregnant and nonpregnant cows.

Animals↗
PubMed1995

Familial macrothrombocytopenia with unusually elongated mitochondria.

We report a familial case of macrothrombocytopenia without inclusion bodies in polymorphonuclear cells or any congenital abnormalities. The results of the hemostatic and platelet function tests were all normal except for the platelet retention rate. The number of megakaryocytes increased slightly and some were relatively small. Electron microscopic studies revealed a unique morphological abnormality of the platelets' mitochondria.

Adult↗