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Biomedical subjects

Masaki Fujimura

Publications and source records attributed to Masaki Fujimura.

At least 73 records · Page 4Linked to original sources
PubMed2003

A free radical initiator, 2,2'-azobis (2-aminopropane) dihydrochloride enhances hyperthermia-induced apoptosis in human uterine cervical cancer cell lines.

Hyperthermia-induced apoptosis and its enhancement in the presence of a temperature-dependent free radical initiator, 2,2'-azobis (2-aminopropane) dihydrochloride (AAPH) were examined in human uterine cervical cancer cell lines, CaSki and HeLa. When both cell lines were treated with hyperthermia at 44 degrees C for 60 min, minimal apoptosis was observed. When combined with nontoxic AAPH (50mM), significant enhancement of apoptosis was observed, where the initial rate of free radical formation was about twice as high than that at 37 degrees C. Augmentation of the growth delay, lipid peroxidation (LPO), activation of caspase-3 and increase in [Ca2+]i were also observed after the combined treatment. A water-soluble vitamin E, Trolox, blocked the increase in [Ca2+]i and an intracellular Ca2+ chelator, BAPTA-AM, prevented the DNA fragmentation induced by the combination. Cytochrome c release was also revealed by fluorescence microscopy. However, no significant change in mitochondrial membrane potential and expression of Bax and Bcl-2 was observed. A slight increase in Fas expression was observed only in CaSki cells after the combined treatment. These results indicate that hyperthermia and AAPH induce enhanced apoptosis and subsequent cell killing via two pathways; a pathway dependenton increase in LPO and [Ca2+]i, and a pathway associated with cytochrome c release and subsequent caspase activation without changes of mitochondrial membrane potential and Bax/Bcl-2 expression in these cell lines. Since it is known that cancer cells are generally resistant to physical and chemical stress-induced apoptosis, free radical generators like AAPH appear to be a useful thermosensitizer for hyperthermic cancer therapy.

Amidines↗
PubMed2003

Serotonin stimulates endotoxin translocation via 5-HT3 receptors in the rat ileum.

Because few previous studies have investigated the mechanisms of endotoxin translocation induced by intestinal obstruction, we aimed to clarify whether or not serotonin [5-hydroxytryptamine (5-HT)], which is released from enterochromaffin (EC) cells, is responsible for alterations of the mucosal permeability to endotoxin and to identify the 5-HT receptor subtypes that mediate this action. FITC-labeled LPS (FITC-LPS) was injected into the ileum of rats, and the FITC-LPS level in the superior mesenteric vein was subsequently measured by using a fluorescence spectrophotometer. To measure the 5-HT release induced by high intraluminal pressure, ex vivo preparation of vascularly and luminally perfused rat ileum was used. Results demonstrated that elevated intraluminal pressure stimulates the translocation of FITC-LPS and the release of 5-HT from the EC cells into the intestinal lumen but not into the portal circulation. This FITC-LPS translocation, which was stimulated by exogenously applied 5-HT in the lumen and the jugular vein, was inhibited by 5-HT(3) receptor antagonist administration both intaluminally and intravenously. The stimulatory effect of elevated intraluminal pressure on the translocation of FITC-LPS was inhibited by the intraluminal and intravenous administration of 5-HT(3) receptor antagonist. These results suggest that 5-HT released from EC cells may be involved in the translocation of FITC-LPS induced by elevated intraluminal pressure and that this effect is mediated by 5-HT(3) receptors that may be located in the intestinal epithelium.

Animals↗
PubMed2003

[A case of pulmonary tuberculosis initially presented with syndrome of inappropriate secretion of antidiuretic hormone (SIADH)].

A 90-year old man was admitted to a hospital because of consciousness loss with hyponatremia. Although his symptom promptly improved with Na supply, his chest X-ray film showed pulmonary infiltration and direct microscopy of sputum smear was positive for acid-fast bacilli, then he was referred our hospital and was admitted. We made a clinical diagnosis of pulmonary tuberculosis with SIADH based on detailed examinations. But he should neither respiratory symptoms nor fever. He was medicated with the standard antituberculosis drugs with fluid restriction, and his tuberculosis and hyponatremia were improved gradually. We should be more careful about pulmonary tuberculosis irrespective of its severity as a cause of SIADH.

Aged↗
PubMed2003

[A case of broncho-pulmonary aspergillosis complicated by bronchial asthma attack].

A 55-year-old man was hospitalized for the treatment of severe asthma. However, his condition improved with steroid chemotherapy under artificial ventilation, but high fever and multiple patchy shadows of the lung that were not responsive to antibiotics appeared. We detected aspergillus hyphae, probably inhaled with a quantity of dust in the attic of his workplace, in the sputum. We diagnosed invasive broncho-pulmonary aspergillosis complicated with allergic broncho-pulmonary aspergillosis. His condition improved with anti-fungal drug treatment. We consider that the causes of invasive broncho-pulmonary aspergillosis in this case were massive inhalation of aspergillus conidia, artifical ventilation and steroid chemotherapy.

Anti-Inflammatory Agents↗
PubMed2003

Airway eosinophil accumulation on sensory neuropeptide release in a guinea pig model of distilled-water-induced bronchoconstriction.

BACKGROUND: Increased numbers of eosinophils in the airways is characteristic of asthma. However, it remains unclear whether airway eosinophils enhance or reduce the release of neuropeptides in the airways in vivo. This study was conducted to elucidate the influence of airway eosinophil accumulation on the ultrasonically nebulized distilled water (UNDW)-induced bronchoconstriction in our newly developed animal model, which is mediated by sensory neuropeptides. METHODS: Guinea pigs were transnasally treated with 100 mg/kg of platelet activating factor (PAF), or vehicle, twice a week for 3 weeks. We then conducted three experiments. In the first, UNDW was inhaled 20 min after aerosolized antigen challenge, and bronchoalveolar lavage (BAL) was performed in PAF-treated and passively sensitized animals. In the second, PAF-treated animals were exposed for 20 s to ascending doses of methacholine at intervals of 5 min In the third, passively sensitized animals were administered selective NK1 antagonist, SR 140333, selective NK2 antagonist, SR 48968, or vehicle, intravenously 5 min before UNDW-induced bronchoconstriction. RESULTS: The proportion of eosinophils in BAL fluid was significantly increased in guinea pigs treated with PAF, compared with the vehicle. The PAF treatment did not affect antigen-induced immediate asthmatic response, UNDW-induced bronchoconstriction, or bronchial responsiveness to inhaled methacholine. SR 140333, but not SR 48968, inhibited the UNDW-induced bronchoconstriction. CONCLUSION: We conclude that eosinophils accumulated in the airways, caused by repeated intranasal administration of PAF, does not affect the release of substance P induced by UNDW inhalation, or the action of released substance P in vivo.

Aerosols↗
PubMed2003

[Influence of smoking on longitudinal decline in one-second forced expiratory volume in clinically healthy Japanese men: a longitudinal study].

We prospectively studied 2140 clinically healthy men to assess the influence of smoking on longitudinal decline in one-second forced expiratory volume (FEV1.0). All the subjects had annual medical checks including pulmonary function tests from 1995 to 1999. The mean values +/- standard deviations of annual decreases in FEV1.0 (slope) were 22 +/- 49 mL/year in non-smokers, 26 +/- 52 mL/year in former smokers, and 33 +/- 57 mL/year in current smokers (p < 0.01; non-smokers vs. current smokers). The adjusted slope (slope divided by predicted value of FEV1.0, per year) in current smokers was also greater than that in non-smokers (p < 0.01). Multiple regression analysis revealed that initial age, height, FEV1.0, and smoking status were significant parameters for determining the slope. This study clearly showed that smoking is an important risk factor foracceleration of the aging-related longitudinal decline in pulmonary function in Japanese men.

Adult↗
PubMed2002

Alpha(1L)-, but not alpha(1H)-, adrenoceptor antagonist prevents allergic bronchoconstriction in guinea pigs in vivo.

alpha-Adrenoceptors have been classified into alpha(1)- and alpha(2)-adrenoceptors. Recently, the alpha(1)-adrenoceptors were divided into two subtypes: alpha(1L) with low affinity and alpha(1H) with high affinity for prazosin. Little is known concerning the role of each subtype of alpha(1)-adrenoceptor in asthma. We investigated the effects of specific antagonists of alpha(1)- and alpha(2)-, alpha(1H)-, alpha(1L)-, and alpha(2)-adrenoceptors, namely moxisylyte, prazosin, 3-[N-[2-(4-hydroxy-2-isopropyl-5-methylphenoxy) ethyl]-N-methylaminomethyl]-4-methoxy-2, 5, 6-trimethylphenol hemifumarate (JTH-601), and yohimbine, respectively, on antigen-induced airway reactions in guinea pigs. Fifteen minutes after intravenous administration of moxisylyte (0.01, 0.1 or 1 mg/kg), prazosin (0.01, 0.1, 1 or 10 mg/kg), JTH-601 (1, 3, 6 or 10 mg/kg) or yohimbine (0.1 or 1 mg/kg), passively sensitized and artificially ventilated animals received an aerosolized antigen challenge. Bronchial responsiveness to inhaled methacholine was assessed as the dose of methacholine required to produce a 200% increase in the pressure at the airway opening (PC(200)) in non-sensitized animals. JTH-601 and moxisylyte, but not prazosin or yohimbine, dose dependently inhibited antigen-induced bronchoconstriction. None of the tested drugs altered PC(200). JTH-601 significantly reduced leukotriene C(4) levels in bronchoalveolar lavage fluid obtained 5 min after antigen challenge, but prazosin did not. These results indicate that prevention of antigen-induced bronchoconstriction by blockade of alpha-adrenoceptors is due to the inhibition of mediator release via alpha(1L)-adrenoceptor antagonism.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed2002

MR-guided microwave thermocoagulation therapy of liver tumors: initial clinical experiences using a 0.5 T open MR system.

PURPOSE: To utilize a microwave coagulator for MR-guided interstitial thermal therapy of liver tumors as a clinically feasible heating device. MATERIALS AND METHODS: MR-guided microwave thermocoagulation therapy was carried out 34 times in 30 patients with liver tumors (eight hepatocellular carcinoma, 22 metastatic tumors) using a 0.5 T open configuration MR system. RESULTS: Percutaneous puncture could be accomplished both accurately and safely while monitoring real-time magnetic resonance imaging (MRI). Using a notch filter, MR images could be observed without electromagnetic interference even during microwave ablation. Temperature monitoring during ablation was possible using the proton resonance frequency method. All procedures could be successfully carried out without any complications, and the therapeutic effects were deemed satisfactory. CONCLUSION: MR-guided microwave thermocoagulation therapy could be one promising procedure of minimally invasive treatment for liver tumors.

Adult↗
PubMed2002

Treatment for patients with postmenopausal osteoporosis who have been placed on HRT and show a decrease in bone mineral density: effects of concomitant administration of vitamin K(2).

We have been using hormone replacement therapy (HRT) as the treatment of choice for menopausal symptoms and osteoporosis. Estrogen increases bone mineral density (BMD) for 2 or 3 years, and only maintains BMD thereafter. In the present study, we investigated whether BMD improved with HRT in combination with vitamin K(2). Ninety-four patients with postmenopausal osteoporosis were studied. All patients were placed on HRT for more than 1 year. Ten patients whose BMD had increased up to a plateau and showed a decreasing trend thereafter while they were receiving HRT were placed on HRT in combination with vitamin K(2). The long-term BMD (L(2)-L(4)) profiles of those receiving HRT alone, and the effects of HRT in combination with vitamin K(2) on the BMD profiles were examined. The rate of change in BMD (mean +/- SE) of all patients who underwent HRT alone was 2.9 +/- 1.2% 1 year after the initiation of HRT, 4.6 +/- 1.2% 2 years later, and 5.4 +/- 1.2% 3 years later. The BMD in these patients, which reached a peak increase after 3 years, no longer increased from the following year. When vitamin K(2) was administered concomitantly to 10 patients for 12 months because of the decrease in BMD, their BMD (mean +/- SE) increased significantly, from 0.734 +/- 0.021 g/cm(2) to 0.783 +/- 0.026 g/cm(2) ( P < 0.03; paired- t test). We conclude that HRT in combination with vitamin K(2) significantly improved BMD that was on the decrease after HRT alone. Therefore, as a supplementary drug for postmenopausal osteoporosis, vitamin K(2) is a good therapeutic option for patients who are placed on HRT.

Bone Density↗
PubMed2002

Colocalization of NO and VIP in neurons of the submucous plexus in the rat intestine.

Since very few previous studies have carried out the quantitative analysis for the colocalization of nitric oxide (NO) and vasoactive intestinal peptide (VIP) in the submucous neurons in the rat digestive tract, we applied in vivo treatment of colchicine to enhance the immunoreactivity and examined the colocalization of NO synthase (nNOS) and VIP in neurons of the submucous plexus throughout the rat digestive tract. The density of nNOS-containing neurons in the submucous plexus in the stomach corpus (103+/-25 cells/cm(2), n=3) and that in the antrum (157+/-9 cells/cm(2), n=3) were significantly lower than those in small and large intestine. However no difference was detected in the cell density among duodenum (1967+/-188 cells/cm(2), n=3), jejunum (2640+/-140 cells/cm(2), n=3), ileum (2070+/-42 cells/cm(2), n=3), proximal colon (2243+/-138 cells/cm(2), n=3) and distal colon (2633+/-376 cells/cm(2), n=3). The proportion of nNOS-immunoreactive (IR), nNOS/VIP-IR and VIP-IR neurons to the total number of submucous neurons was examined. nNOS/VIP-IR neurons comprised 45-55% of total number of submucous neurons from the duodenum to the proximal colon, however those comprised 66.4+/-5.1% in the distal colon. The results showed that the dense distribution of nNOS-containing neurons was found in the submucous plexus throughout the small and large intestine, and large population of submucous neurons co-stored nNOS and VIP.

Animals↗
PubMed2002

Total video endoscopic thyroidectomy via the anterior chest approach using the cervical region-lifting method.

Endoscopic surgery offers superior cosmetic results compared to open procedures and is strongly preferred by many patients, especially women. We performed total endoscopic thyroidectomy via the anterior chest approach using a neck skin-lifting technique in which the skin is lifted by a large number of hooks to create the working space. This method is quite flexible and can be modified based on the size of the space needed. The fine hooks leave no scar on the anterior neck, the skin incisions are small, and the scars are completely covered by patients' undergarments. Endoscopic thyroidectomy is suitable for benign thyroid nodules, but some malignant foci diagnosed by frozen section usually can be managed without conversion to an open procedure. Women under 45 years of age with nodules <2 cm who have no evidence of lymphatic spread or local invasion are ideal candidates for this procedure.

Adolescent↗
PubMed2002

Distributions of endometrial NK cells, B cells, T cells, and Th2/Tc2 cells fail to predict pregnancy outcome following recurrent abortion.

PROBLEM: To evaluate the ability of immunophenotypes of endometrial leukocytes from patients with histories of recurrent abortion to predict outcome of subsequent pregnancy. METHODS OF STUDY: Seventeen women with two successive spontaneous abortions with normal karyotype in the conceptus and 15 women with male-factor infertility were studied. Subsequent pregnancy outcomes in 17 recurrent abortion patients were noted; 11 had live birth, while six aborted in the first trimester. All of 15 women with male-factor infertility became pregnant after therapy, resulting in live birth in all cases. Endometrium was sampled during the peri-implantation period before subsequent pregnancy. We immunostained paraffin-embedded sections for lymphocyte markers including natural killer (NK) cell markers, CD56 and CD16, a B-cell marker CD20, T-cell markers CD3 and CD8, and a specific T-helper(Th)2 and T-cytotoxic (Tc)2 marker termed 'chemoattractant receptor-homologous molecule expressed on Th2 cells' (CRTH2). Immunoreactive cells for these antigens were counted and positivity ratios to CD45- or CD3-positive cells were calculated. These parameter were compared between 17 patients with histories of recurrent abortion and 15 control women and also compared between 11 patients whose subsequent pregnancy was successful and six patients whose subsequent pregnancy was a failure. RESULTS: Numbers of CD45+, CD56+, CD16+, CD20+, CD3+, CD8+, and CRTH2+ cells in recurrent abortion patients resembled those in controls. No significant difference in lymphocyte subset numbers or ratios was noted between patients whose subsequent pregnancy was successful and those who again aborted. CONCLUSION: We could not predict pregnancy outcome by immunophenotypic analysis of endometrium in women with recurrent abortion.

Abortion, Habitual↗
PubMed2002

Interleukin 2 receptor gamma chain (gamma(c)) knockout mice show less regularity in estrous cycle but achieve normal pregnancy without fetal compromise.

PROBLEM: Implication of cytokines in pregnancy suggested but remains to be established. We studied the effect of cytokines on reproductive functions such as ovulation and pregnancy, with mutant mice lacking interleukin 2 receptor gamma (IL-2Rgamma), the so-called common gamma chain (gamma(c)), which is shared among receptors for multiple cytokines such as IL-2, IL-4, IL-7, IL-9 and IL-15. METHOD OF STUDY: Regularities of estrous cycles were observed by vaginal smear. Ovaries stimulated with postmenopausal serum gonadotropin (PMSG) were examined for the ovarian capacities. The uteri at 13 days of gestation were used for histological analysis of the maternal-fetal interface. RESULTS: The estrous cycles in gamma(c) knockout (gamma(c) KO) mice were irregular compared with wild-type mice, although, the mutants could become pregnant. No uterine natural killer (uNK) cell was found in the uterus at 13 days of pregnancy, and poor decidual formation and thickness of blood vessel walls were observed. Apparent differences were not seen in the numbers and weight of the fetuses between wild type and mutant animals, and fetuses were not compromised throughout pregnancy. CONCLUSIONS: The gamma(c) KO mice showed irregular estrous cycle but they could carry out normal pregnancy despite lacking uNK and cytokines actions of IL-2, 4, 7, 9 and 15.

Animals↗
PubMed2002

A Th2 chemokine, TARC, produced by trophoblasts and endometrial gland cells, regulates the infiltration of CCR4+ T lymphocytes into human decidua at early pregnancy.

PROBLEM: A chemokine receptor, CCR4 preferentially expressed on type 2 helper T (Th2-type) cells, and its ligand, thymus and activation regulated chemokine--(TARC/CCL)--play important roles in the recruitment of Th2-type cells. We examined the distribution of CCR4 expressing CD4+ and CD8+-T cells in human decidua at early pregnancy, and localized TARC in the decidual tissue and chorionic tissue. METHOD OF STUDY: Decidual tissue was obtained by legal abortion. The percentages of CCR4 expressing CD4+ and CD8+-T cells were analyzed by flow cytometry. Localization of TARC protein was evaluated by immunofluorescence staining. The expression of TARC mRNA in the choriocarcinoma cell line and endometrial cell line was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR). RESULT: The percentages of CCR4+ cells in CD4+-T cells and CD8+-T cells were significantly increased in human early pregnancy decidua compared with those in peripheral blood. An another marker of human Th2 and Tc2 cells, CRTH2 molecules was also expressed on CCR4+ CD4+-T cells and CCR4+ CD8+-T cells. In addition, we found that trophoblasts, uterine epithelial cells and endometrial gland cells produce TARC by immunohistochemical staining and the RT-PCR method. CONCLUSION: Our findings imply that TARC secreted in decidua mediates the infiltration of CCR4+ T-cell migration into the fetomaternal interface, decidua, resulting in the maintenance of pregnancy.

Adult↗
PubMed2002

Effect of candesartan, a type 1 angiotensin II receptor antagonist, on bronchial hyper-responsiveness to methacholine in patients with bronchial asthma.

AIMS: Angiotensin II is a putative mediator in bronchial asthma. There have been very few studies investigating the involvement of angiotensin II receptors in bronchial hyper-responsiveness in asthmatic patients. We examined the effect of candesartan cilexetil, a specific angiotensin II type 1 (AT1) receptor antagonist, on bronchial responsiveness to inhaled methacholine in patients with asthma. METHODS: Bronchial responsiveness to methacholine, assessed as the concentration of methacholine producing a 20% fall in FEV1 (PC20-FEV1), was measured on three occasions 2 weeks apart in 11 stable asthmatic patients. Candesartan cilexetil (8 mg once a day) or a placebo was orally administered for 1 week before the methacholine provocation test in a double-blind, randomized, crossover manner. RESULTS: Although there were no significant differences between treatment periods in FEV1 values at baseline, the geometric mean (95% CI) PC20-FEV1 values increased significantly (P = 0.041) from 0.691 (0.379, 1.259) mg ml-1 with placebo to 0.837 (0.506, 1.384) mg ml-1 with candesartan. Candesartan decreased the mean (95% CI) arterial blood pressure (placebo: 95.6 (89.0, 102.2) mmHg, candesartan: 86.4 (79.8, 93.1) mmHg, P = 0.015). There was no correlation between the change in blood pressure and the change in PC20-FEV1. CONCLUSIONS: We conclude that AT1 receptors are involved in bronchial hyper-responsiveness in asthmatic patients.

Administration, Inhalation↗
PubMed2002

Addition of a 2-month low-dose course of levofloxacin to long-term erythromycin therapy in sinobronchial syndrome.

BACKGROUND: We previously reported that a 6-month low-dose course of ofloxacin combined with long-term low-dose erythromycin therapy (EM therapy) was superior to EM therapy alone for sinobronchial syndrome (SBS), especially during the initial 2 months of treatment. However, there was no data as to whether discontinuation of low-dose ofloxacin after 2 months results in symptom relapse. This study was designed to clarify this issue. METHODOLOGY: Twenty-three patients with SBS received a 2-month course of levofloxacin (LVFX) therapy (100 mg once a day) concurrent with a 6-month course of EM therapy (200 mg three times a day) (group A). Eighteen other patients were given the EM therapy alone (group B). Clinical parameters, including quantity of morning sputum, were recorded in a daily symptom diary, and reviewed by each doctor in charge at 2-4 week intervals. RESULTS: The quantity of morning sputum decreased more rapidly in group A than in group B. No relapse of symptoms was recognized after discontinuation of LVFX in group A. CONCLUSIONS: A 2-month low-dose course of LVFX in conjunction with long-term EM therapy may be efficacious for the treatment of SBS, as evidenced by rapid improvement of expectoration without any relapse after LVFX discontinuation.

Aged↗
PubMed2002

Effect of ozagrel hydrochloride, a thromboxane synthetase inhibitor, on alcoholic beverage-induced bronchoconstriction in asthmatic patients.

Acetaldehyde is thought to be a main factor of alcohol-induced asthma. The thromboxane (TX) synthetase inhibitor, ozagrel hydrochloride, inhibits acetaldehyde-induced bronchoconstriction in asthmatic patients. The present study evaluated the involvement of TXA(2) on alcoholic beverage-induced bronchoconstriction. Four patients with alcohol-induced asthma received ozagrel (400 mg for 4 days) or placebo using a single-blind, randomized, cross-over design. On two separate study days, each subject drank the same brand and volume of alcoholic beverage (beer or Japanese sake) and bronchoconstriction was assessed as the change in peak expiratory flow (PEF). The effect of ozagrel on the aerosolized challenge of acetaldehyde was investigated in the same subjects. Although aerosolized acetaldehyde-induced bronchoconstriction was significantly prevented by ozagrel, there were no differences in the time course of the decrease in PEF or the maximum fall in PEF after alcohol intake between placebo and ozagrel. We conclude that TXA(2) is not involved in alcoholic beverage-induced bronchoconstriction.

Acetaldehyde↗