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Biomedical subjects

Y Morimoto

Publications and source records attributed to Y Morimoto.

At least 253 records · Page 14Linked to original sources

In vitro/in vivo difference in enhanced skin permeation of nicardipine hydrochloride by the 1-menthol-ethanol system.

The in vitro/in vivo difference in enhanced skin permeation of nicardipine hydrochloride (NC) by simultaneous use of 1-menthol and ethanol (MEW system, 1-menthol:ethanol:water = 5:40:55) was investigated in hairless rats. First, the cutaneous blood flow clearance (clearance from skin to blood flow) of NC per unit area of skin (CLCB/A), which was comparable to the permeability coefficient across skin (PC), was calculated from intracutaneous and intravenous injection data using the deconvolution method; the value was 1.67 microliters/h/cm2. Two formulations containing NC and the MEW system, solution (SOL) and 15% hydroxypropyl cellulose gel (GEL), were used for in vitro and in vivo permeation experiments. The in vitro PC of NC via excised skin from SOL (23.3 microliters/h/cm2) was significantly higher than CLCB/A, and that from GEL (1.48 microliters/h/cm2) was similar to CLCB/A. Consequently, the steady-state concentration of NC in skin during in vivo application of SOL was 6.6 times higher than corresponding in vitro data. In vivo PCs from SOL and GEL were however significantly lower than CLCB/A. These results may be explained by the findings, using a laser Doppler flowmeter, that cutaneous blood flow was decreased by the application of MEW.

Animals↗

Acute changes in intracranial pressure and pressure-volume index after forebrain ischemia in normoglycemic and hyperglycemic rats.

BACKGROUND AND PURPOSE: Hyperglycemia enhances the deleterious effect of global cerebral ischemia. One possible explanation is that increased anaerobic glycolysis leads to exaggeration of intracellular acidosis and increased postischemic edema. To examine the importance of this edema on postischemic cerebral perfusion dynamics, we measured acute changes in intracranial pressure (ICP), specific gravity, and the pressure-volume index (PVI) after forebrain ischemia in normoglycemic and hyperglycemic rats. METHODS: Rats underwent 15 minutes of forebrain ischemia and 90 minutes of reperfusion. ICP and mean arterial pressure were continuously monitored. Before ischemia, rats received either saline or glucose intravenously. Ninety minutes after ischemia, the specific gravity of the neocortex was measured. In a second experiment, the PVI was measured at 20 and 60 minutes after ischemia. RESULTS: Preischemic ICP (mean+/-SD) was 7 +/- 1 mm Hg in both groups. A peak ICP (approximately 11 mm Hg) occurred within 15 to 20 minutes after ischemia in both groups. Between 25 and 80 minutes after ischemia, ICP was significantly but only slightly greater in hyperglycemic than in normoglycemic rats. Cerebral perfusion pressure was similar between groups and remained greater than 100 mm Hg. Specific gravity was also similar for both groups but was less than normal values. The PVI in hyperglycemic rats was lower than in normoglycemic rats, indicating reduced compliance. CONCLUSIONS: These findings indicate that hyperglycemia-augmented intraischemic tissue acidosis does not contribute to worsened outcome by means of compromised cerebral perfusion pressure during the early stages of recovery. Nevertheless, evidence was found for decreased cerebral compliance, indicating an effect of hyperglycemia on intracranial volume compartments other than cortical parenchyma.

Animals↗

Comparison of Two Questionnaires on Respiratory Symptoms in a Nicaraguan Population: Value in Diagnosis of Chronic Bronchitis.

Two questionnaires about respiratory symptoms were evaluated for reliability and ability to diagnose chronic bronchitis in a study population of 129 Nicaraguans (110 workers and 19 patients with chronic bronchitis). The first questionnaire (AQ) had symptom questions that were based on British Medical Research Council (MRC) questions, adapted to local Spanish. The second questionnaire (MRCQ) contained MRC symptom questions translated directly into Spanish. The reliability of the questions was measured in a test-retest procedure. The questionnaire-based diagnosis of chronic bronchitis was compared with the diagnosis made by a physician (for workers) or from the hospital records (for patients). The questions concerning symptoms in both questionnaires were of acceptable reliability. For the diagnosis of chronic bronchitis in workers, the AQ showed similar sensitivity, a somewhat higher specificity, and a substantially higher positive predictive value (90%) than the MRCQ (57%). Among the patients, the AQ identified 17 patients as positive (sensitivity 89%), while the MRCQ identified 15 (sensitivity 79%). respiratory questionnaire; reliability; chronic bronchitis; Nicaragua Hanley & Belfus, Inc. Int J Occup Environ Health 1077-3525 2 2 1996 April/June Chronic Exposure to Cigarette Smoke Inhibits the Stimulating Effects of Mineral Fibers on the Production of Tumor Necrosis Factor by Alveolar Macrophages of Rats 95 98 EN Yasuo Morimoto Department of Environmental Health Engineering, University of Occupational and Environmental Health, Japan 1-1, Iseigaoka, Yahatanishiku, Kitakyushu 807, Japan. Ziro Nambu Hajime Hori Tohru Tsuda Hiroshi Yamato Toshiaki Higashi Yasuyuki Yokosaki Masamitsu Kido Isamu Tanaka The objective of this study was to evaluate the chronic combined effects of mineral fibers and cigarette smoke on the production of tumor necrosis factor (TNF) by alveolar macrophages. The authors chronically exposed ten rats to cigarette smoke in vivo and measured the production of TNF by alveolar macrophages in the presence of mineral fibers in vitro. For smoke exposure, rats were divided into two groups. Five rats were exposed daily to a concentration of 10 mg/m(3) of cigarette smoke for six hours a day, five days a week, for four weeks, and five rats (control) were not exposed to smoke. A broncho-alveolar lavage was performed after the smoke exposure, and the recovered alveolar macrophages were incubated with either chrysotile or ceramic fibers on a microplate for 24 hours. TNF activity in the supernatant was determined by the L929 bioassay. When alveolar macrophages were not stimulated by mineral fibers, TNF production tended to be lower in smoke-exposed alveolar macrophages than in unexposed ones, although the difference was not significant statistically. When alveolar macrophages were stimulated in vitro by chrysotile or ceramic fibers, both fibers stimulated TNF production, but TNF production in smoke-exposed alveolar macrophages was lower than that in unexposed macrophages. These results revealed that long-term exposure to cigarette smoke inhibited the stimulating effect of mineral fibers on the production of TNF.

Journal Article↗

Analysis of in vitro iontophoretic skin permeation of sodium benzoate by transport numbers of drug and additives.

Effect of species and concentrations of pharmaceutical additives on the iontophoretic transport of benzoate anion through excised hairless rat skin was investigated using a 2-chamber iontophoretic diffusion cell equipped with platinum electrodes at 0 mA for 4h (control) followed by a constant direct current of 0.5 mA for another 4h. One cell facing the stratum corneum was filled with sodium benzoate solution, and the other cell facing the dermis with lithium chloride (LiCl), potassium chloride (KCl) or tetraethylammonium bromide (TEA-Br) solution. Iontophoretic delivery rate of benzoate anion that permeated through skin increased with an increase in the sodium benzoate concentration while maintaining a constant KCl concentration. In contrast, a flux of benzoate anion decreased with an increase in KCl concentration and a constant concentration of sodium benzoate. When KCl was replaced by LiCl or TEA-Br, the flux of benzoate anion was almost the same. These phenomena were evaluated by a concept of transport numbers: theoretical values of benzoate anion flux were very close to the observed data. Potential difference between the skin during the permeation study was also measured between two salt bridges which were connected via calomel electrodes to a potentiometer. It gradually decreased to a certain level in each case, but increased again in some cases. This gradual decrease and increase in the potential difference, in spite of a constant current, were theoretically explained by a gradual increase of ion concentration in the skin membrane and depletion of the cation in the receiver cell, respectively. Analysis of ionic mobility and concentration of penetrants gave a great deal of information on iontophoretic drug permeation through skin.

Animals↗

Difference in the enhancing effects of ultrasound on the skin permeation of polar and non-polar drugs.

The effect of ultrasound (150 kHz, 111 mW/cm2) on the permeability of isosorbide dinitrate (ISDN) and antipyrine (ANP) through excised hairless rat skin was evaluated using an Arrhenius plot. The permeability coefficients of ISDN across skin (at various temperatures) in the presence and absence of ultrasound were virtually isolinear on the Arrhenius plot. It has been suggested that the temporal increase in the ISDN flux, which was observed when ultrasound was applied in our previous study, was only a result of the thermal effect of ultrasound, i.e., an increase in the temperature of the donor solution. On the other hand, ultrasound influenced the Arrhenius plot of ANP, suggesting that the enhancement effect for ANP permeation could be not explained only by the thermal effect of ultrasound. In addition, the effective diffusion (D) and partition coefficients (K) of ISDN and ANP were estimated using their skin permeation profiles across the ultrasonic pretreated skin. The coefficients of ISDN with ultrasonic pretreatment were comparable to those without pretreatment. On the other hand, the D value of ANP with ultrasonic pretreatment was increased about 4 times by ultrasonic pretreatment, in spite of an insignificant change in the K value. These results suggest that the ultrasound used in the present study increased the effective diffusivity across the aqueous region in the stratum corneum to enhance the skin permeation of the polar compound, ANP.

Animals↗

Environmental tobacco smoke and policies for its control.

This study evaluated the effect of designated smoking areas in an office and the efficacy of air cleaners in a smoking room. The concentrations of suspended particulates (SP) were measured at 13 points in the office, including the smoking room, corridors around the smoking room, and a non-smoking office. The SP concentrations were between 0.52 to 1.31 mg/m3 in the smoking room, 0.06 to 0.22 mg/m3 in the corridors and 0.03 to 0.05 mg/m3 in the non-smoking office, respectively. The results showed that the area restriction on smoking in this office was successful, although an outflow of tobacco smoke was observed in the corridors. The SP concentration in the smoking room where three electrostatic air cleaners had been installed was monitored over 24 hours. The SP concentration due to tobacco smoke in the smoking room was much greater than the control concentration of SP in air-conditioned buildings in Japan, that is, not more than 0.15 mg/m3. The effectiveness of electrostatic air cleaners in closed smoking rooms is discussed.

Air Pollution, Indoor↗

[Treatment of postoperative nausea and vomiting with ondansetron in patients administered anti-neoplastic agents].

The antiemetic effect of ondansetron (a 5-HT3 antagonist) was evaluated in patients treated with intraperitoneally administered anti-neoplastic agents (cisplatin and mitomycin-C) during surgery for ovarian cancer. Anesthesia was induced with intravenous thiopental 5 mg x kg-1 and maintained with nitrous oxide 66% in oxygen and isoflurane. After surgery, 6 patients received a single intravenous dose of ondansetron 4 mg (group O), 6 others did not receive ondansetron (group C). Both groups received an intravenous dose of methyl-prednisolone 500 mg. An intravenous dose of metoclopramide 10 mg was provided in case of continued vomiting or at the patient's request as a rescue antiemetic. The incidence of vomiting was 13% in group O and 87% in group C (P < 0.05). Nausea scores (range 1-4) were significantly lower in group O as compared with group C at 4 h and 8 h after surgery. Total dose of metoclopramide was 20 +/- 13 mg (mean +/- SD) in group C and 2 +/- 4 mg in group O. Administration of anti-neoplastic agents during surgery caused severe nausea and vomiting after surgery and ondansetron prevented the occurrence of nausea and vomiting almost completely. We conclude that ondansetron is an effective antiemetic for preventing postoperative nausea and vomiting in patients administered anti-neoplastic agents.

Adult↗

Association analysis of a polymorphism of the monoamine oxidase B gene with Parkinson's disease in a Japanese population.

The polymorphic allele of the monoamine oxidase B (MAO-B) gene detected by polymerase chain reaction (PCR) and single-stranded conformation polymorphism (SSCP) was associated with Parkinson's disease (PD) in Caucasians. We characterized this polymorphic allele, allele 1, of the MAO-B gene using direct sequencing of PCR products. A single DNA substitution (G-A), resulting gain of Mae III restriction site was detected in intron 13 of the MAO-B gene. The allele associated with PD in Caucasians was twice as frequent as in healthy Japanese, but the association of the allele of the MAO-B gene was not observed in Japanese patients with PD.

Adult↗

Activation of hepatocyte growth factor by two homologous proteases, blood-coagulation factor XIIa and hepatocyte growth factor activator.

Hepatocyte growth factor (HGF) is secreted as an inactive single-chain precursor from the producing cells, and normally remains in this form associated with the extracellular matrix. In response to tissue injury, the single-chain precursor is converted to a biologically active heterodimer by a serine protease, the activity of which is induced in the injured tissue. We have previously identified HGF activator, a serum serine protease that activates single-chain HGF. The sequence of HGF activator cDNA revealed that the HGF activator is homologous to blood-coagulation factor XIIa. In this study, we found that coagulation factor XIIa has an ability to activate single-chain HGF. Factor XIIa exhibited a significant level of HGF-converting activity in the presence of dextran sulfate, although the specific activity of factor XIIa was slightly lower than that of the HGF activator. Since factor XIIa is activated during the initiation of contact activation induced by tissue injury, factor XIIa may function as an HGF-converting enzyme together with HGF activator in the injured tissue. C1-inhibitor, antithrombin III and alpha 2-antiplasmin, that regulate the blood-clotting activity of factor XIIa, were also effective against the HGF-converting activity of factor XIIa. Furthermore, factor XIIa was not active in the HGF-converting activity in serum. Thus, the HGF-converting activity of factor XIIa may be regulated by these serum inhibitors.

Factor XIIa↗

A case of early gastric malignant lymphoma diagnosed and completely resected by strip biopsy.

A case of early gastric malignant lymphoma definitively diagnosed by strip biopsy is reported. The subsequent operation revealed that the strip biopsy had resulted in radical resection. A 55-year-old woman visited our hospital for detailed examination of a small gastric lesion. Histologic findings of the specimens obtained by conventional forceps biopsy indicated reactive lymphoid hyperplasia, although the possibility of malignant lymphoma was not completely ruled out. Strip biopsy was, therefore, performed to establish a definitive diagnosis. Histopathological examinations of the strip biopsy specimen revealed definitive findings of malignant lymphoma, which was B-cell phenotype immunocytochemically. The margin of the resected specimen was free of invasion by malignant lymphoma and no lymph node involvement was suggested by endoscopic ultrasonography, computed tomography, and gallium scintigram. Subtotal gastrectomy was subsequently performed to rule out the possibility of remaining malignant lymphoma cells. It was proven that the strip biopsy removed the lesion completely and no perigastric lymph nodes were involved. While is still controversial as to whether strip biopsy should be adopted for the radical resection of early gastric lymphoma, this procedure can definitely provide excellent specimens for the accurate diagnosis of gastric malignant lymphoma and probably for group III lesions in the stomach.

Biopsy↗

Effects of nickel oxide on the production of tumor necrosis factor by alveolar macrophages of rats.

To evaluate the effect of green nickel oxide (NiO) on the production of tumor necrosis factor (TNF) by alveolar macrophages, alveolar macrophages were exposed to NiO in vitro and in vivo. For the in vitro study, rats alveolar macrophages were incubated with NiO on a microplate for 24 h. TNF activity in the culture supernatant was determined by the L929 bioassay. Rats alveolar macrophages cultured with 100 and 200 micrograms/mL of NiO in vitro induced the production of TNF, however, it was not statistically significant compared with the control that was free from NiO exposure. For exposure in vivo, rats were divided into two groups. Five were exposed to a daily concentration of 11.7 +/- 2.0 mg/m3 of NiO for an 8-hr/d, 5 d/wk, for 4 wk, and five rats (control) were kept in a cage and not exposed to NiO. Bronchoalveolar lavage was performed and the recovered alveolar macrophages were incubated on a microplate for 24 h. TNF production by exposed alveolar macrophages was significantly higher than that of controls.

Acid Phosphatase↗

Iridoid glucosides from the leaves and stems of Duranta erecta.

From the leaves of Duranta erecta, four new iridoid glucosides, duranterectosides A, B, C and D, were isolated along with durantosides I and II, lamiide, lamiidoside and verbascoside. Duranterectoside A was also isolated from the stems together with durantosides I, II and III, and lamiidoside. The structures of the new compounds were elucidated based on the spectroscopic evidence.

Carbohydrate Conformation↗

Ordered structure of the crystallized bovine 20S proteasome.

Eukaryotic proteasomes are multicatalytic proteinase complexes with a molecular weight of 750 kDa, containing, respectively, two copies of a hetero-heptamer of alpha-type subunits and one of beta-type subunits, (alpha 1-7 beta 1-7)2. Proteasome was purified from bovine liver and crystallized into a hexagonal system with cell dimensions of a = b = 121.83(2) A, c = 930.68(6) A. A cylindrical particle size of 122 A diameter and 155 A height was determined from the molecular packing in a unit cell. The crystal gave diffraction spots up to at least 4.4 A resolution, which was the minimum spacing of the camera used. The overall temperature factor of the enzyme was estimated to be in the range of 36.2 to 25.8 A2. These results imply that the enzyme complex has a unique ordered structure comprising multisubunits with two types of hetero-heptamer. This ordered structure may facilitate highly organized cooperation of individual functions of subunits within the enzyme complex.

Amino Acid Sequence↗

A histological study of cutaneous thermal wounds using a Clostridium perfringens-derived wound healing substance with wound healing stimulation activity.

We studied the effects of a Clostridium perfringens-derived wound-healing substance (WHS) on the healing of thermal burn wounds. Third-degree burn injuries were inflicted on the back skin of rats. We histologically evaluated the effects of WHS ointments and compared them with those of lysozyme chloride ointment. We observed the formation of dermal collagen fibers and the increase of capillaries in the WHS ointment treated groups. From the results of hematoxylin and eosin staining and silver staining, an increase in capillaries was observed one week after the application of WHS ointment. Three weeks after the application, when the epithelization was in the final stage, capillary formation ceased. In the WHS ointment-applied groups, electron microscopic observation showed that new collagen fibers were regularly formed in the dermis. On the other hand, in the lysozyme chloride ointment-applied groups, new collagen fibers were present, but were irregularly formed. The main wound healing stimulative action of the WHS ointment could be due to its acceleration of new capillary formation.

Animals↗

Proliferating activity of the hair follicular melanocytes at the early and anagen III stages in the hair growth cycle: detection by immunocytochemistry for bromodeoxyuridine combined with DOPA reaction cytochemistry.

In order to demonstrate the existence of proliferating activity in hair follicular melanocytes during the early and anagen III stages, immunocytochemistry for bromodeoxyuridine (BrdU) incorporated in the nuclei of the melanocytes for 1 hr was undertaken at the light and electron microscopic levels in combination with DOPA reaction cytochemistry. Light microscopically, about 30% of the nuclei of the DOPA reaction positive melanocytes at the anagen III stage of the hair growth cycle were labeled by anti-BrdU antibody. These melanocytes were observed in about one hundred hair follicles. Electron microscopically, the nuclei of a few undifferentiated melanocytes at the anagen II stage were labeled by anti-BrdU antibody-affiliated secondary antibody-gold particles. At the anagen III stage, localization of the immunogold particles in the DNA replication domains of the nuclei of the undifferentiated and redifferentiating melanocytes covered the patterns of the early, middle, and late S-phase. These findings suggest that the hair follicular melanocytes begin proliferation at the anagen II stage and that the melanocytes proliferate actively at the anagen III stage to repopulate the hair matrix during subsequent hair growth.

Animals↗

Effect of KBT-3022, a new diphenylthiazole derivative, on platelet functions.

The effects of KBT-3022 and its metabolite desethyl KBT-3022 on platelet aggregation were determined in rat, guinea-pig, rabbit and human platelets in-vitro and ex-vivo. KBT-3022 and desethyl KBT-3022 inhibited platelet aggregation induced by arachidonic acid and collagen in-vitro more potently than aggregation induced by adenosine diphosphate, platelet-activating factor or thrombin, as well as by acetylsalicylic acid, and their effects were approximately 100 times more potent than those of acetylsalicylic acid. Desethyl KBT-3022, but not KBT-3022 or acetylsalicylic acid, inhibited thrombin-induced aggregation and 5-hydroxytryptamine release from platelets more potently than ticlopidine hydrochloride at higher concentrations. Oral administration of KBT-3022 inhibited both arachidonic acid- and collagen-induced platelet aggregation and reduced platelet retention in a glass-bead column approx. 100 times more potently than acetylsalicylic acid. KBT-3022 showed little or no anti-inflammatory effect on either ultraviolet-induced erythema or arachidonic acid induced ear oedema, and had lower gastro-ulcerogenicity than acetylsalicylic acid. These results suggest that KBT-3022 is a potent inhibitor of platelet activation with weak side-effects.

Adenosine Diphosphate↗

Acute interstitial nephritis and uveitis with bone marrow granulomas and anti-neutrophil cytoplasmic antibodies.

Acute interstitial nephritis (AIN) and uveitis of unknown etiology developed in a 15-year-old girl. Symptoms and urinary abnormalities improved spontaneously but moderate renal dysfunction and anterior uveitis persisted. A repeat biopsy performed 2 years later showed focal tubulointerstitial changes, while bone marrow examination revealed granulomas. Simultaneously, antineutrophil cytoplasmic antibodies (ANCA) were detected, and decreases in T cell population and lymphocyte function were found. These immunological abnormalities normalized in parallel with clinical improvement with corticosteroid therapy, strongly suggesting that in some patients autoimmune disorders contribute to the pathogenesis of the disease.

Acute Disease↗