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Biomedical subjects

K Miyamoto

Publications and source records attributed to K Miyamoto.

At least 145 records · Page 8Linked to original sources
PubMed2000

Retinoic acid (RA) represses follicle stimulating hormone (FSH)-induced luteinizing hormone (LH) receptor in rat granulosa cells.

The present study was undertaken to identify the mechanisms underlying the effect of retinoic acid (RA) on the luteinizing hormone receptor (LH-R) in rat granulosa cells. Treatment with FSH produced a substantial increase in LH-R mRNA level, as was expected, while concurrent treatment with increasing concentrations of RA brought about dose-dependent decreases in FSH-induced LH-R mRNA. RA, either alone or in combination with FSH, did not affect intracellular cAMP levels, while it inhibited the effect of 8-Br-cAMP on LH-R mRNA production. Whether the effect of RA and FSH on LH-R mRNA levels was the result of decreased transcription and/or altered mRNA stability was also investigated. The rate of LH receptor mRNA gene transcription, assessed by nuclear run-on transcription assay, was inhibited by the addition of RA. The effect of RA on LH-R mRNA stability was determined by measuring the decay of LH receptor mRNA under conditions known to inhibit transcription. The decay curves for the 5.4-kb LH-R mRNA transcript showed a significant decrease after the addition of RA. It may be possible that RA not only inhibits FSH-induced transcription but also stimulates the production of destabilizing factors for the LH-R mRNA. These findings assist in understanding the molecular mechanism underlying the effect of RA on reproductive function in rat granulosa cells.

Animals↗
PubMed2000

Inhibitory effect of Coptidis Rhizoma and berberine on the proliferation of human esophageal cancer cell lines.

Our previous study demonstrated that the herbal medicine, Oren-to, had antitumor effects on esophageal cancer cells (ECCs) in vitro. The purpose of this study was to examine which of the seven constituents of Oren-to had antitumor effects on esophageal cancer cells. MTT assay showed that, of the seven constituents, only the aqueous extract of Coptidis Rhizoma had potent inhibitory effect on the proliferation of two types of ECC lines, YES-3 and YES-4. In addition, the proliferation of all six types of ECC lines (YES-1 to YES-6) was inhibited in a dose-dependent manner (P<0.001 for all), when co-cultured at each concentration of Coptidis Rhizoma for 72 h. The ID50 of Coptidis Rhizoma for YES-1 to YES-6 was 2.2 microg/ml, 3.0 microg/ml, 0.25 microg/ml, 2.8 microg/ml, 2.5 microg/ml, and 0.5 microg/ml, respectively, berberine, one of protoberberine components of Coptidis Rhizoma, showed potent antitumor effects on all six types of ECC lines as well as Coptidis Rhizoma. In addition, the ID50 of berberine showed a positive correlation with that of Coptidis Rhizoma in six types of ECC lines examined (r2 = 0.763, P = 0.023). Cell cycle analysis of Coptidis Rhizoma-treated cancer cells showed the accumulation of cells in the G0/G1 phase and relative decrease of the S phase. These results support the possibility that the use of Coptidis Rhizoma containing abundant berberine may be useful as one of alternative therapies for esophageal cancers.

Antineoplastic Agents↗
PubMed2000

Modulatory roles of RANTES in IL-4 production by human blood CD4(+)T cells.

An increase in serum IgE levels has been reported in several thrombotic cardiovascular diseases. Since such diseases are associated with the activation of platelets, we hypothesized that platelets are implicated in a mechanism leading to heightened IgE synthesis. To this end, we performed an in vitro investigation of the effects on IL-4 production caused by several bioactive substances potentially released from platelets. Human blood CD4(+)T cells from blood donors were stimulated with anti-CD3 antibody and costimulatory signals delivered via CD58 and CD80 in the presence or absence of IL-4. One of the following test substances was also included in the culture: platelet factor-4, beta-thromboglobulin, platelet-derived growth factor, serotonin, platelet activating factor, or RANTES. The cells were restimulated in the absence of IL-4 and test substances. Among the six substances, RANTES alone exhibited significant effects on IL-4 production. RANTES enhanced IL-4 production in the presence of IL-4, whereas it suppressed IL-4 production in the absence of IL-4. The enhancing effect of RANTES was positively correlated with plasma IgE levels in the donors. We concluded that RANTES may induce IgE synthesis by increasing IL-4 production in individuals predisposed to high IgE responses. Our observations indicate a link between platelets and immune phenomena associated with increased IgE responses.

Adult↗
PubMed2000

Health surveillance in the population living in a methyl mercury-polluted area over a long period.

It is important to follow up on the health status of inhabitants living in the methyl mercury-polluted area surrounding Minamata City, paying particular attention to diseases not only of the central nervous system but also of other organs. We have been carrying out such concentric studies for more than 10 years. We have previously studied the cause-specific standard mortality ratios in Minamata disease patients and reported that the SMRs for liver disease and renal disease were significantly raised in male and female patients, respectively. It was also found that complications arising from diabetes could be due to the large number of old people among the autopsy cases. The next step was to clarify the actual prevalence and incidence of liver disease, renal disease, and diabetes mellitus epidemiologically among the population in this area. The aim of this study was to determine the actual prevalence of these diseases and complaints, and to investigate the contribution of various risk factors to these diseases in this area. The study was a population-based cross-sectional mass screening survey. A case-control study was designed to estimate the role of various risk factors including methyl mercury exposure for these diseases. A mass multiple health examination survey was performed in 1500 subjects aged 40 years and older in Tsunagi Town, neighboring Minamata City, every summer since 1984. Tsunagi Town is located in a methyl mercury-polluted area and there are 36.9 certified Minamata disease patients per 1000 population. Data concerning liver disease, renal disease, and diabetes mellitus were collected on the basis of urine, hematological, physical, and ultrasonographic examinations. Data on risk factors and subjective complaints were collected by interview and other measures. The prevalence of these diseases was not higher in this methyl mercury-polluted area compared with other areas in Japan, contrary to what was expected based on standard mortality ratios and pathological findings. There were no positive correlations between those diseases and methyl mercury exposure. On the other hand, the population in the polluted area had more and a greater variety of complaints than those in the nonpolluted area. It is possible that not only neurological subjective complaints but also nonspecific complaints of the population in the polluted area might be influenced by past methyl mercury exposure. This health surveillance in the population living in a methyl mercury-polluted area must be maintained in the future.

Aged↗
PubMed2000

A brief course of colon preparation with oral antibiotics.

We carried out a prospective clinical trial of colon preparation with a regimen of oral antibiotics starting on the day before surgery. The patients were assigned to one of two groups consisting of either a mechanical preparation alone group (group 1, 45 cases) or a mechanical bowel preparation with oral antibiotics group (group 2, 38 cases). Group 2 received kanamycin and metronidazole three times on the day before surgery. Cefmetazole was administered for 3 consecutive days as prophylaxis in both groups. In a study using intraoperative mucosal swabs, the rates of group 2 patients with cultures yielding anaerobes or Gram-negative bacteria were significantly lower than those of group 1. There were no significant differences in the rates of patients with cultures yielding fungi or Gram-positive organisms. The positive culture rate in the peritoneal fluid of group 1 was also higher than that of group 2 (40%, 16%, P < 0.05). The surgical site infection rate was 18% in group 1 and 13% in group 2. Organisms isolated from the sites of postoperative infections were not identical with those from the peritoneal fluid. This relatively brief course preparation minimized the emergence of resistant strains. However, in spite of the colonic bacterial burden and the intraoperative inoculation in the patients with mechanical cleansing alone, their incidence of subsequent infections was comparable to that of patients who were administered oral antibiotics provided that the prophylactic antibiotic was administered for 3 days after surgery.

Administration, Oral↗
PubMed2000

The differential cardioprotective effects of nucleoside transport inhibitor on moderate and deep hypothermic ischemia with cold cardioplegia.

The differences in the cardioprotective effects of nucleoside transport inhibitor (NTI) which is known to accumulate endogenous adenosine, on moderate and deep hypothermic ischemia, were examined. Using the Langendorff model, isolated, perfused rat hearts were arrested with cold cardioplegia and subjected to 90 min of global ischemia followed by 40 min of reperfusion. The temperature during ischemia was maintained at either 10 degrees C (groups 1 and 2) or 25 degrees C (groups 3 and 4). In groups 2 and 4, NTI in the form of R75231, 1 mg/l, was added to the cardioplegic solution. The intramyocardial adenosine triphosphate content at the end of ischemia was significantly lower in the moderate hypothermia groups than in the deep hypothermia groups. In the moderate hypothermia groups, NTI significantly enhanced the adenosine accumulation at the end of ischemia. Moreover, the recovery of both the contractile function and coronary flow rate in group 4 was superior to that in group 3, and was similar to those in groups 1 and 2. The addition of NTI to the cardioplegic solution generated a sufficient cardioprotective effect in moderate hypothermic ischemia, but not in deep hypothermic ischemia. The mechanism of this discrepancy is attributed to the differences in the levels of endogenous adenosine accumulated during ischemia.

Adenine Nucleotides↗
PubMed2000

Impact of anatomical difference of the cerebral venous system on microcirculation in a gerbil superior sagittal sinus occlusion model.

Sinus-vein thrombosis (SVT) is known to have a wide spectrum of clinical manifestations, and the formation of venous collateral pathways is considered to be one of the most important factors influencing the individual outcome. Here, we examined the relationship between the anatomical differences in bridging veins and cerebral microcirculation in a gerbil superior sagittal sinus (SSS) occlusion model. In male Mongolian gerbils (n=26), the SSS was ligated close to the confluence sinuum. Four additional animals served as the sham-operated control. Regional cerebral blood flow (rCBF) and haemoglobin oxygen saturation (HbSO2) were assessed by Laser-Doppler flowmetry and a microspectrophotometric method at 36 identical locations in the both hemispheres every 20 minutes for 120 minutes after ligation using a "scanning" technique. Furthermore, we examined change in the diameter of the bridging vein by fluorescence angiography and brain damage by histological investigation after 48 hours. Based on the anatomical findings, the hemispheres were classified into two groups: group A with one bridging vein, n=24/52 sides (46.2%) and group B with more than two bridging veins, n=28/52 sides (53.8%). Significant decreases in rCBF (P<0.05) and rHbSO2 (P<0.05) were seen from 20 minutes after the ligation to the end of the experiment in group A, but not in group B. A detailed analysis of individual cases in changes of local (l) CBF and lHbSO2 revealed three patterns: 1) pattern-1, no change; 2) pattern-2, decrease with following recovery; 3) and pattern-3, decrease without recovery. There were no significant differences in the diameter of the bridging vein and no venous infarction in either groups. The group A frequency, which consisted of pattern-3 (58.3%)>pattern-2 (29. 2%)>pattern-1 (12.5%), was opposite to that of group B, which consisted of pattern-1 (71.4%)>pattern-2 (25.0%)>pattern-3 (3.6%) (P<0.001). Based on the results of this study, the anatomical structure and an opening of the collateral pathways of the venous drainage system are closely related to microcirculatory alterations after venous occlusion. The experimental model is suitable for the study of the pathophysiological mechanism responsible for the high variability of SVT.

Animals↗
PubMed2000

CD18 and ICAM-1-dependent corneal neovascularization and inflammation after limbal injury.

Extensive limbal injury is a leading cause of irreversible blindness. The destruction of corneal limbal stem cells often results in corneal neovascularization and an optically inferior epithelium. Previous work has shown that the neovascularization after limbal injury is vascular endothelial growth factor (VEGF)-dependent, with much of the VEGF emanating from the inflammatory cells that invade the cornea. Using a relevant mouse model of limbal injury, we examined the role of CD18 and intercellular adhesion molecule-1 (ICAM-1) in limbal injury-induced neovascularization. The results show that CD18- and ICAM-1-deficient mice developed 35% (n = 5, P = 0.003) and 36% (n = 5, P = 0.002) less neovascularization than strain-specific normal controls, respectively. The corneal neutrophil counts were similarly reduced by 51% (n = 5, P < 0.003) and 46% (n = 5, P < 0.006), respectively. When VEGF mRNA levels were analyzed, they were reduced by 66% (n = 3, P = 0.004) and 48% (n = 3, P = 0.024), respectively. Taken together, these data identify CD-18 and ICAM-1 as mediators of the inflammatory and VEGF-dependent corneal neovascularization that follows limbal injury. The targeting of CD18 and ICAM-1 may prove useful in the treatment of inflammation-associated neovascularization in the cornea and elsewhere.

Animals↗
PubMed2000

Vascular endothelial growth factor (VEGF)-induced retinal vascular permeability is mediated by intercellular adhesion molecule-1 (ICAM-1).

Two prominent vascular endothelial growth factor (VEGF)-induced retinal effects are vascular permeability and capillary nonperfusion. The mechanisms by which these effects occur are not completely known. Using a rat model, we show that intravitreous injections of VEGF precipitate an extensive retinal leukocyte stasis (leukostasis) that coincides with enhanced vascular permeability and capillary nonperfusion. The leukostasis is accompanied by the up-regulation of intercellular adhesion molecule-1 expression in the retina. The inhibition of intercellular adhesion molecule-1 bioactivity with a neutralizing antibody prevents the permeability and leukostasis increases by 79% and 54%, respectively. These data are the first to demonstrate that a nonendothelial cell type contributes to VEGF-induced vascular permeability. Additionally, they identify a potential mechanism for VEGF-induced retinal capillary nonperfusion.

Acridine Orange↗
PubMed2000

Sleep bruxism in patients with sleep-disordered breathing.

The aim was to test the hypothesis of a direct association between sleep-disordered breathing and sleep bruxism. The frequency of masseter contraction (MC) episodes and rhythmic jaw movements (RJM) was measured in patients with mild and moderate obstructive sleep apnoea (OSA). The diagnosis of sleep bruxism was made from a combination of questionnaire, clinical observation and all-night polysomnographic recording which included masseter electromyography. A total of 21 patients (19 males/two females, mean age 40.0 years+/-9.2 SD) were randomly selected from a provisional diagnosis of snoring and OSA by a sleep physician. In the patients with mild OSA [n=11, mean apnoea hypopnoea index (AHI)=8.0+/-4.1 SD, body mass index (BMI)=29.1+/-5.0], the diagnosis of sleep bruxism was made in six out of 11 patients (54%); similarly, four out of 10 patients (40%) with moderate OSA (n=10, mean AHI=34.7+/-19.1, BMI=30.6+/-5.0) were identified as bruxists. Although the combination of clinical, subjective estimation and nocturnal electromyographic recording of masseter muscle might provide a more solid base for the diagnosis of sleep bruxism, the result is biased by the variation in the bruxing activity. MC episodes were associated with the termination of apnoea or hypopnoea episodes in only 3.5% of the mild group and 14.4% of the moderate group (p<0.05). It appears that sleep bruxism is rarely directly associated with apnoeic events, but is rather related to the disturbed sleep of OSA patients.

Adult↗
PubMed2000

Expression of steroidogenic acute regulatory protein (StAR) in rat granulosa cells.

Steroidogenic acute regulatory protein (StAR) is a vital mitochondrial protein that is indispensable for the synthesis of steroids. To study the mechanisms of regulation of StAR in rat granulosa cells, we used granulosa cells obtained from diethylstilbestrol-treated immature rats. Northern blot analysis revealed two major transcripts of about 3.6 kb and 1.6 kb of rat StAR mRNA. Rat StAR mRNA had strongly increased within 2 h due to the treatment of FSH or 8-Br-cAMP in this culture, a parallel increase of transcripts of both sizes was observed. Compared to the control, StAR mRNA levels increased in a dose-dependent manner in the presence of increasing concentrations of FSH (1-100 ng/ ml) and 8-Br-cAMP (0.25-5 mM). Although co-treatment of rat granulosa cells with FSH and TGF-beta did not change FSH-induced StAR mRNA levels, these levels in granulosa cells were markedly increased by pretreatment with TGF-beta before being acutely (2 h) stimulated with an effective dose of FSH. The stimulatory effect of TGF-beta was time- and concentration-dependent (1-30 ng/ml).

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2000

Lack of interaction in recombinant human FSH receptor and both TSAb and TSBAb.

Since cross-reactivity of TSH with the human FSH receptor has been reported, in this study we tested the effect of thyroid-stimulating antibody (TSAb) and thyroid stimulation-blocking antibody (TSBAb) on Chinese hamster ovary cells expressing human FSH receptor (CHO-hFSH-R cells). We examined the TSBAb activity of sera from hypothyroid patients who had a positive TBII to determine whether these sera also block the effect of FSH on CHO-hFSH-R cells. Although human FSH I-3 (0.25-16 ng/ml) stimulated the production of intracellular cAMP in CHO-hFSH-R cells with dose-responsive manner, neither TSAb nor TSBAb had such an effect on the cells.

Adult↗
PubMed2000

Detection of plasmalogen from plasma low density lipoprotein and high density lipoprotein in carp, Cyprinus carpio, and rainbow trout, Oncorhynchus mykiss.

The study revealed the presence of plasmalogens in the low density lipoprotein (LDL) and high density lipoprotein (HDL) of the fish. The composition of the plasmalogen in the carp plasma LDL phospholipids was 0.94 and 0.23% in the HDL; the LDL phospholipids in the rainbow trout were 0.44% and the HDL was 0.18%. Aldehydes from the plasmalogen were derivatized with dansylhydrazides and separated by high performance liquid chromatography (HPLC). Their presence was detected using a fluorescence detector. Hexadecanal (C16: 0), octadecanal (C18: 0) and octadecenal (C18: 1) were determined to be the major components in the carp and rainbow trout.

Animals↗
PubMed2000

Structural study of the sodium channel inactivation gate peptide including an isoleucine-phenylalanine-methionine motif and its analogous peptide (phenylalanine/glutamine) in trifluoroethanol solutions and SDS micelles.

In order to gain insight into the gating mechanisms of Na+ channels, in particular their inactivation mechanisms, we studied the structures of the Na+ channel inactivation gate related peptide which includes the IFM (Ile-Phe-Met) motif (Ac-KKKFGGQDIFMTEEQKK-NH2; K1480-K1496 in rat brain type-IIA Na+ channels, MP-3A) and its F/Q(Gln) substituted one (MP-4A) in trifluoroethanol (TFE) solutions and sodium dodecyl sulfate (SDS) micelles using circular dichroism (CD) and 1H-NMR spectroscopies. Based on observed nuclear Overhauser effect constraints, three-dimensional structures of MP-3A and MP-4A were determined using simulated annealing molecular dynamics/ energy minimization calculations. In TFE solutions, no appreciable differences in the structure were observed using either CD or NMR spectra. In SDS micelles, however, the two peptides exhibited definitely different structures from each other. It was found that in MP-3A, residues 11488 and T1491 were spatially proximate with each other owing to hydrogen bonding between the amide proton of 11488 and the hydroxyl oxygen atom of T1491, whereas in MP-4A, F/Q substitution separated them owing to conformational changes. The solvent-accessible surfaces calculated for the structures of MP-3A and MP-4A showed that the former has a smoother interaction surface to the hydrophobic docking site than the latter. In conclusion, the conformational changes, as well as decreased hydrophobicity around the IFM motif owing to the F/Q mutation, may be one reason why F1489Q mutated channels cannot inactivate almost completely.

Amino Acid Motifs↗