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Biomedical subjects

K Morimoto

Publications and source records attributed to K Morimoto.

At least 343 records · Page 19Linked to original sources

Calcium antagonistic vasodilator mechanisms of brovincamine fumarate studied in canine cerebral artery.

In order to elucidate the major mechanism of cerebral vasodilator action of brovincamine fumarate (CAS 57475-17-9) the present study was performed comparing its effects with those of d-cis-diltiazem in the isolated canine basilar artery. Brovincamine possessed a wide spectrum of inhibitory actions on the contractions of the artery produced by various spasmogens and mechanical stretch. Brovincamine was 3 to 40 times less potent than d-cis-diltiazem in the inhibitory actions. Simultaneous recordings of intracellular Ca2+ concentration and mechanical activity showed that brovincamine and d-cis-diltiazem decreased both parameters augmented by high KCl in a concentration-dependent and parallel manner. Both brovincamine and d-cis-diltiazem shifted parallel to the right the concentration-response curves for CaCl2-induced contraction of the artery constructed in the Ca(2+)-free depolarizing medium. Furthermore, Schild regression of the curves was linear with a slope of unity, indicating apparently a competitive antagonism between Ca2+ channel function/Ca2+ and brovincamine or d-cis-diltiazem. The results suggest that the cerebral vasodilator effect of brovincamine is mainly attributable to the inhibition of Ca2+ influx through the voltage-dependent Ca2+ channels, supporting the reported clinical benefits of this drug in the treatment of cerebrovascular disorders.

Animals↗

[A case of mediastinal emphysema due to blunt trauma that a continuous drainage to the extrapleural space took effect].

A 70-year-old male was admitted to our hospital with chest bruise, resulting in fracture of the right rib. Nine hours later, the patient came to use again with a chief complaint of dyspnea and chest oppression. He had extensive subcutaneous emphysema in the upper half of the body. Chest X-ray films revealed remarkable mediastinal emphysema and collapse in a part of right lung. Chest CT scan disclosed enlargement of extrapleural cavity. These findings suggested progression of mediastinal emphysema. Continuous drainage to the extrapleural cavity was performed and the clinical course was uneventful. Thus, a satisfactory result can be obtained by extrapleural drainage in a patient with severe mediastinal emphysema.

Aged↗

Effects of an anti-platelet drug (dilazep) in IgA nephropathy: comparison of clinical effects with renal biopsy findings.

To investigate renal biopsy findings arising in response to treatment with an anti-platelet drug in IgA nephropathy, 46 patients were treated with dilazep dihydrochloride (Dilazep), and a retrospective comparison was performed between the clinical effects and renal biopsy findings. After 6 months of treatment, 18 patients (39%) were judged to be improved if their proteinuria was ameliorated by a 25% or greater decrease with improved or persistent renal function. The group of improved patients exhibited mean decreased levels of urinary proteins in the range from 1.9 to 0.8 g/day after treatment (p < 0.01). By contrast, the unimproved group showed increased urinary proteins in the range from 1.2 to 2.0 g/day (p < 0.05). The improved group showed histological findings with fewer glomeruli exhibiting sclerosis and/or cellular crescents, with a lesser increase in mesangial matrix and with smaller tubulo-interstitial lesions than the unimproved group. By immunofluorescence, the improved group was found to have smaller amounts of glomerular IgA and IgG deposits. These findings suggest that an anti-proteinuric effect of Dilazep administration can be expected in patients with IgA nephropathy with relatively mild glomerulo-sclerotic lesions.

Adult↗

[A case of perforated mitral valve aneurysm following aortic valve replacement associated with infective endocarditis].

A case of perforated mitral valve aneurysm following aortic valve replacement associated with infective endocarditis was reported. The patient was a 29-year-old man, who was suffering from high fever, Osler's nodules and headache. A brain abscess was recognized in a computed tomography and 3rd grade aortic regurgitation was recognized in echocardiogram and aortography. Hematological studies suggested the inflammation and gram-positive cocci was incubated from his arterial blood. Then infective endocarditis with aortic regurgitation was diagnosed. AVR was performed following 8 weeks treatment with antibiotics, when he had negative CRP and his blood culture. After the operation, he was received the intravenous antibiotic therapy for 6 weeks and oral antibiotic drugs was given following his hospital discharge. At 6 months after AVR, mitral valve aneurysm was recognized in his echocardiogram. At 30 months after AVR, the perforation of it was revealed and mitral valve replacement was performed with his negative blood culture. The patient was discharged 28th day after MVR. There has been no active inflammation from his first hospital discharge and following days, the mitral valve aneurysm and the perforation was caused by weakened tissue of the anterior mitral leaflet due to sibilant inflammatory change.

Adult↗

[Treatment with arbekacin of surgical infections by resistant strains of Staphylococcus aureus. Arbekacin Study Group].

The frequency of infection by methicillin-resistant Staphylococcus aureus (MRSA) is high in Japan and control of such strains is urgently needed. Arbekacin (ABK), a semisynthetic aminoglycoside, has potent activity against S. aureus, including resistant strains, and against Gram-negative bacteria as well. For this reason, in surgical infections (which are often caused by more than one bacterium), this drug might be particularly effective. We calculated the MIC and the decrease in the MIC when cultures of 59 resistant strains of S. aureus isolated in our wards at Osaka City University Hospital, contained arbekacin in the medium. We also used the drug to treat 12 infections caused by resistant strains of S. aureus. The MICs of vancomycin had a single peak at 0.5 microgram/ml, and those for ABK had double peaks at 0.5 and 4.0 micrograms/ml. The effect of arbekacin in lowering the MIC of minocycline (MINO) was slight because of the low MIC of MINO. Effects on fosfomycin (FOM), ampicillin, clavulanic acid/ticarcillin, cefotiam, cefuzonam, flomoxef, and imipenem/cilastatin were strong; the peaks were lowered by 1/2(7)-1/2(11). When 1.0 micrograms/ml ABK was present in the medium, the efficacy of FOM was increased enough that, by prediction from the pharmacokinetics of FOM (blood level when given at the usual dose), all but one (2%) of the 47 resistant strains would be eradicated clinically. If 2.0 micrograms/ml ABK were in the medium, all strain would be eradicated, by our calculations. We treated 11 infections and one colonization by resistant strains of S. aureus with ABK and evaluated the response in these cases of infection. Four infections were treated with FOM as well. The clinical efficacy was good in four infections (three patients), fair in four, and poor in three, for an efficacy rate of 36%. All presumed causative bacteria were eradicated in two (18%) of the 11 infections and S. aureus strains were eradicated in three (27%) of the 11 infections. No symptoms of side effects were reported, but blood urea nitrogen and creatinine rose in a 72-year-old woman with duodenal perforation and peritonitis. The MIC levels of ABK were satisfactory, but clinical efficacy for staphylococcal infections caused by resistant strains was unsatisfactory.

Adult↗

[DNA content analysis and detection of c-myc and p53 products using flow cytometry in resected lung cancer cases].

We quantitatively analyzed the c-myc and p53 products using flow cytometry in 28 cases of resected lung cancer and one case each of chorio-carcinoma, plasmacytoma, malignant mesothelioma and sclerosing hemangioma. In the lung cancer cases, c-myc and p53 products were detected in 10 cases (35%) and 7 cases (21%), respectively. These rates are higher than the DNA abnormal expression rates of the c-myc and p53 genes (15% and 12%, respectively) in our own data. In the adenocarcinoma of lung cancer cases, c-myc and p53 products were detected in 9 cases (53%) and 5 cases (29%), respectively. Among the squamous cell carcinoma cases, there were one case (11%) of c-myc expression and one case (11%) of p53 expression. DNA content analysis of the lung cancer patients revealed 7 cases of DNA diploidy and 21 cases of DNA aneuploidy. All 10 c-myc-positive cases showed DNA aneuploidy; thus the positive rate for c-myc products in the DNA aneuploidy cases was significantly different compared with the DNA diploidy cases (p < 0.05). In the sclerosing hemangioma case, we detected both c-myc and p53 products. Sclerosing hemangioma has been thought to be a benign tumor, but it may be a malignant tumor.

Adenocarcinoma↗

[A late phase II study of CPT-11 (irinotecan) in advanced breast cancer. CPT-11 Study Group on Breast Cancer].

A late phase II study of CPT-11 for advanced breast cancer was conducted at 27 institutions. Seventy-nine patients were enrolled, 75 were eligible for the study, and 65 were evaluable for efficacy. One complete response and 14 partial responses were obtained, and the response rate was 23%. The response rate of patients with prior endocrine therapy and prior chemotherapy including adriamycin or other anthracycline drugs was 27% (11/41) and 26% (12/46), respectively. The response rate for patients with estrogen receptor-negative tumors and premenopausal patients was 32% (6/19) and 27% (4/15), respectively. Responses were observed not only for soft tissue lesions such as lymph nodes (5/17), but also for distant metastases in the lungs (8/28) and bone (1/18). The major adverse reactions were myelosuppression and gastrointestinal symptoms. The incidence of Grade 2 or higher leukopenia, anemia, nausea/vomiting, anorexia, diarrhea and alopecia was 68%, 31%, 67%, 59%, 37%, and 30%, respectively. These results suggested that CPT-11 was a promising drug for advanced breast cancer.

Adult↗

[An in vivo DNA adduct database for carcinogens: O6-alkylguanine, O4-alkylthymine and 8-hydroxyguanine].

Many carcinogens react with DNA and form critical DNA adducts, such as O6-alkylguanine (O6-AG), O4-alkylthymine (O4-AT), and 8-hydroxyguanine (8-OHG). This study provides a database that can be used for molecular dosimetry of these DNA adducts. A literature survey on DNA binding in vivo was done by the Dialog search from the MEDLINE database. We propose a Critical Covalent Binding Index (CCBI) for the assessment of in vivo DNA binding level (expressed as micro mol chemical bound per mol G or T/mmol chemical administered per kg body weight). The number of records and compounds in parenthesis of O6-AG, O4-AT, and 8-OHG were 245(13), 54(4), 79(15), respectively. Since the CCBI values for N-nitrosamine in target organ were higher than for non-target organ, they may provide a useful index for estimation of target organ site and carcinogenic potency. As a case example, CCBI values for O4-AT from animal data were applied for diethylnitrosamine human exposure estimation by diethylnitrosamine.

Animals↗

Spin trapping of superoxide released by opsonized asbestos from human promyelocytic leukemia cell line, HL60.

By ESR using 5,5-dimethyl-1-pyrroline-1-oxide as a spin trap, superoxide (O2-) production was proved upon stimulation of dimethyl sulfoxide-differentiated HL60 by crocidolite opsonized with fresh or refrigerated serum, as well as by phorbol myristate acetate (PMA). Crocidolite, unopsonized or opsonized with frozen-thawed or heat-inactivated serum, did not induce O2- release. Addition of iron chelators or superoxide dismutase inhibited O2- release completely. Neither undifferentiated nor PMA-differentiated HL60 released O2- upon stimulation with opsonized crocidolite.

Asbestos↗

Role of urokinase type plasminogen activator (u-PA) in corneal epithelial migration.

The role of plasminogen activator (PA) in the migration of corneal reepithelialization was studied. Rabbit corneal blocks were cultured, and both the extent of epithelial migration over the exposed corneal stroma and the activity of PA released into the culture media were measured. A significant, direct correlation between epithelial migration and PA activity in the medium was observed, even when the migration was stimulated by fibronectin or EGF, or was inhibited by cytochalasin B or cycloheximide. Zymography confirmed that the PA released into the culture medium was of the urokinase type (u-PA). Immunohistochemical studies showed that u-PA and plasmin(ogen) were present at the leading edge of the migrating epithelium. Studies of corneal cell cultures indicated that epithelial cells rather than endothelial cells or fibroblasts were the source of the u-PA. The addition of antihuman u-PA IgG or protease inhibitors retarded the migration of the corneal epithelium in a dose-dependent manner, indicating that u-PA activity is essential for the migration of the corneal epithelium. These findings suggest that the migration of corneal epithelial cells requires not only cell attachment to the extracellular matrix through the fibronectin but also degradation of the fibronectin by the release of cellular u-PA.

Animals↗

Molecular cloning and sequence of cDNAs for the import precursors of oligomycin sensitivity conferring protein, ATPase inhibitor protein, and subunit c of H(+)-ATP synthase in rat mitochondria.

Four cDNAs for the import precursors of oligomycin sensitivity conferring protein (OSCP), ATPase inhibitor protein (IF1) and subunit cs (encoded by P1 and P2 genes) of rat mitochondrial H(+)-ATP synthase have been cloned from a rat cDNA library. The import precursors and the mature polypeptides of rat OSCP, IF1, subunit c (P1) and subunit c (P2) consisted of 23/190, 25/82, 61/75 and 66/75 amino acids, respectively.

Adenosine Triphosphatases↗

Estrogen stimulates the elaboration of cell/matrix surface-associated inhibitory factor of osteoclastic bone resorption from osteoblastic cells.

Osteoblast-like UMR106 cells secreted bone resorption-stimulating activity (BRSA) under stimulation by human parathyroid hormone 1-34. Most of BRSA was associated with cell/matrix surface and could be extracted by 2 M NaCl. Pretreatment with 17 beta-estradiol (E2) reduced BRSA by enhancing the elaboration of an inhibitory factor of BRSA in a dose-dependent manner, and 10(-9) M 17 beta-E2 showed a significant effect. Neither 17 alpha-E2 nor dihydrotestosterone showed a similar effect. The inhibitory factor of BRSA was also bound to cell/matrix surface, showed affinity for heparin, and was trypsin- and heat-sensitive. Furthermore, this factor could also inhibit resorption pit formation stimulated by 1,25-dihydroxyvitamin D3, interleukin (IL)-1 alpha and IL-6. Elaboration of such an inhibitory factor of bone resorption from osteoblasts may play an important role in the protective effect of estrogen against bone resorption.

Animals↗

Tissue reaction to alumina implants inserted into the tibiae of rats.

We examined the tissue reaction to three alumina implants--single-crystal alumina (SA), dense polycrystal alumina (DPA), and porous polycrystal alumina (PPA)--inserted transcortically, extending into the medullary canal of rat tibiae, and assessed the quantitative differences in bone reaction using an image processing system. There was no difference in the degree of maturation of newly formed bone around the three kinds of alumina. SA and DPA were encapsulated with a continuous bone layer, but some bone tissue was attached focally around PPA. Bone trabeculae in the control site diminished in size and number chronologically. Multinucleated giant cells were observed on the surface of DPA and PPA, but not on SA. Tabulation of the quantitative evaluation indicated that SA showed the highest, DPA a lower, and PPA the lowest in bone contact rate, bone contact thickness, and bone contact area. These data suggest that SA is superior to the other two as an implant material.

Aluminum Oxide↗

Shedding of Gs protein (a soluble form of the viral glycoprotein) by the rabies virus-infected BHK-21 cells.

We investigated a possible mechanism of G protein shedding occurring in the rabies virus-infected BHK-21 cell cultures. Quantitative analysis showed that about 10% of the newly synthesized G proteins were shed from the cells as Gs protein, a soluble form of G protein which lacked the C-terminal anchoring region of the protein, into the culture medium. Pulse-chase experiments revealed that the release of tritium-labeled Gs proteins began soon after the synthesis, but ceased after a short time (within about 2 hr). On the other hand, the release of the virion-associated G protein began 30 to 60 min behind the start of Gs protein shedding and continued for more than 10 hr. Gs protein could not be detected in the cells by biochemical and immunological methods at the time when large amounts of Gs protein were actively being shed. With an antiserum against the C-terminal of G protein we could detect in the cell a polypeptide having a size that is seemingly the same as that which was lost from Gs protein. These results suggest that Gs proteins are generated by a proteolytic cleavage of newly synthesized G proteins, and the cleavage seems to be stopped at a certain stage of the G protein maturation.

Amino Acid Sequence↗

Chromosome alterations in peripheral lymphocytes as indices of lifestyle and genotoxicity.

Short-term cultures of human lymphocytes were used to investigate the in vitro metabolism of benzene and its genotoxicity, and to monitor genetic health effects of lifestyles. Metabolic (S9) activation of benzene and its metabolites, catechol, hydroquinone, and phenol, caused an increase in sister-chromatid exchanges (SCEs) with different optimal concentrations of S9 mix for converting each compound into further reactive forms. The data indicate that catechol and hydroquinone can be optimally metabolized to produce reactive species, presumably benzo(semi)quinones, under conditions of lower metabolic activity than those necessary for phenol and benzene. We have further investigated the correlations between chromosome alterations (SCEs, structural aberrations and micronuclei) in peripheral lymphocytes and individual lifestyles. Healthy lifestyles, or "good health practices" examined were 1) not smoking, 2) not drinking too much alcohol, 3) doing physical exercise regularly, 4) sleeping more than 6 h per night, 5) keeping nutritional balance in meals, 6) not snacking, 7) having breakfast everyday, and 8) not having too much perceived stress. The persons were categorized into 3 groups having good, moderate and poor lifestyles by the number of good health practices they do. Mean frequencies of chromosome alterations in lymphocytes from men with poor lifestyles have been shown to be significantly higher than those in cells from men having good lifestyles.(ABSTRACT TRUNCATED AT 250 WORDS)

Benzene↗