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Biomedical subjects

H Miyamoto

Publications and source records attributed to H Miyamoto.

At least 325 records · Page 18Linked to original sources

Characterization of a novel aquaretic agent, OPC-31260, as an orally effective, nonpeptide vasopressin V2 receptor antagonist.

1. OPC-31260, a benzazepine derivative, has been studied for its ability to antagonize the binding of arginine vasopressin (AVP) to receptors in rat liver (V1) and kidney (V2) plasma membranes, for antagonism of the antidiuretic action of AVP in alcohol-anaesthetized rats and for diuretic action in conscious normal rats. 2. OPC-31260 caused a competitive displacement of [3H]-AVP binding to both V1 and V2 receptors with IC50 values of 1.2 +/- 0.2 x 10(-6) M and 1.4 +/- 0.2 x 10(-8) M, respectively. 3. OPC-31260 at doses of 10 to 100 micrograms kg-1, i.v., inhibited the antidiuretic action of exogenously administered AVP in water-loaded, alcohol-anaesthetized rats in a dose-dependent manner. OPC-31260 did not exert an antidiuretic activity suggesting that it is not a partial V2 receptor agonist. 4. After oral administration at doses of 1 to 30 mg kg-1 in normal conscious rats, OPC-31260 dose-dependently increased urine flow and decreased urine osmolality. The diuretic action of OPC-31260 was characterized as aquaresis, the mode of diuretic action being different from previously known diuretic agents such as furosemide, hydrochlorothiazide and spironolactone. 5. The results indicate that OPC-31260 is a selective V2 receptor antagonist and behaves as an aquaretic agent. OPC-31260 will be a useful tool in studying the physiological role of AVP and in the treatment of various conditions characterized by water retention.

Administration, Oral↗

Investigation of the role of macrophages and endogenous interferon-gamma in natural resistance of mice against Legionella pneumophila infection.

Mice are highly resistant to Legionella pneumophila infection. To study the natural resistance, we used A/J and C57BL/6 mice which have macrophages permissive and non-permissive for the intracellular growth of L. pneumophila, respectively. The LD50 for A/J and C57BL/6 were 2.7 x 10(7) and 7.2 x 10(7) CFU, respectively, indicating that the difference in macrophage ability to regulate the bacterial growth had some effect on susceptibility to L. pneumophila. There was no difference between both strains in elimination of the bacteria from the blood stream within 5 h after infection. When mice were challenged intravenously with a sublethal dose (4 x 10(6) CFU), the bacterial burden in the liver at day 1 was significantly higher in A/J than in C57BL/6. The bacteria, thereafter, were eliminated rapidly from the liver at a similar rate in both strains. Elimination of the bacteria from the spleen and lungs was also delayed in A/J as compared to C57BL/6. Naive spleen cells of both strains in vitro could produce a large amount of interferon-gamma (IFN-gamma) one day after they were stimulated with formalin-killed L. pneumophila. When anti-murine IFN-gamma monoclonal antibody was administered, the bacterial burden in liver, spleen and lungs significantly increased in A/J, and also in C57BL/6 to some extent. We suggest that the innate macrophages' ability to regulate the intracellular bacterial growth and the endogenous IFN-gamma produced in a very early phase play a critical role in murine natural resistance against L. pneumophila infection.

Animals↗

Adult T-cell leukemia/lymphoma (ATL)--clinical, histopathological, immunological and immunohistochemical characteristics.

Twenty-one patients with ATL were assessed. The predominant physical findings were lymph node and bone marrow involvement, skin involvement, hepatosplenomegaly and leukemic manifestations. The predominant histopathological findings in both skin and lymph node specimens were the diffuse medium-sized cell type and the diffuse mixed cell type. Some phenotypic discrepancy was found between the neoplastic cells in the peripheral blood, lymph nodes and skin of patients with ATL with respect to CD45RA and CD45RO, and CD7, CD29, CD25 and HLA-DR. That is, the predominant neoplastic cell phenotype was the helper T-cell, which was CD3+, CD4+, CD7+, CD25+, CD45RA+ and HLA-DR+, and CD29- and CD45RO- in peripheral blood and lymph nodes, and CD3+, CD4+, CD7+, CD29+, CD45RO+ and HLA-DR+, and CD45RA- in the skin. In other words, we have described the phenotypic heterogeneity of ATL cells and demonstrated the heterogeneity of CD45R isoform expression on ATL cells in different organs--the skin, peripheral blood and lymph nodes--of the same patient.

Adult↗

A phase III comparison of etoposide/cisplatin with or without added ifosfamide in small-cell lung cancer.

A total of 92 patients with small-cell lung cancer (SCLC) were randomized to receive cisplatin (80 mg/m2, day 1)/etoposide (100 mg/m2, days 1, 3, 5) (PE) or cisplatin (80 mg/m2, day 1)/etoposide (100 mg/m2, days 1, 3, 5)/ifosfamide (2 g/m2, days 1, 2, 3) (PEI) combination chemotherapy. After 2 courses of chemotherapy, patients with limited disease (LD) received chest irradiation of 40-50 Gy. Of the 89 patients who could be wholly evaluated, the overall response rate was 78% for PE and 74% for PEI therapy (NS). For all patients the complete response (CR) rates were 14 versus 21%, respectively, and 22 versus 30% for LD. However, the median survival times for all patients were 55 weeks for PE therapy versus 56 weeks for PEI therapy (NS). The 2-year survival rates were 15 and 17%, respectively, for all patients (NS). There was no difference in the duration of response between PE and PEI therapy in cases with CR or partial response. However, severe leukopenia (< 2,000/mm3) occurred more often after PEI (73%) than after PE (44%) therapy (p < 0.05). These results suggest that PEI is not superior to PE chemotherapy in SCLC. The use of ifosfamide in multimodality treatment regimens needs to be studied further.

Adult↗

Bellini duct carcinoma of the kidney.

We report a very rare case of Bellini duct carcinoma originating from the collecting tubules of the kidney. A left renal tumor was detected during a health examination and radical nephrectomy was performed. Histological examination showed papillary adenocarcinoma. By means of immunohistochemical methods, we felt that the tumor was a renal carcinoma of Bellini duct origin.

Adenocarcinoma, Papillary↗

Time-related morphological changes of porcine ovarian granulosa cells incubated with urea-EDTA solution.

Morphological profiles of porcine granulosa cells incubated with 10 mM Tris-HCl containing 1 M urea and 5 mM EDTA (urea-EDTA solution) were investigated. The percentages of granulosa cells incorporating the dye, trypan blue on incubation with urea-EDTA solution did not change during the initial 30 min. Thereafter, granulosa cells gradually took up the dye throughout the incubation. The amount of protein released from granulosa cells increased dramatically during initial 15 min of incubation, but decreased during the following 15-30 min of incubation. Thereafter, the amount of proteins released from granulosa cells increased gradually again. The releasing profile of 51Cr-bounded substances in granulosa cells increased markedly during the initial 15 min of incubation, and decreased during the next 15 min of incubation. Subsequently the amount of 51Cr released was enhanced. The min of incubation. Subsequently the amount of 51Cr released was enhanced. The plasma membranes of granulosa cells remained intact at 30 min of incubation, although chromatin clusters of granulosa cells disappeared. Thereafter, a number of cells showed signs of degeneration, including broken plasma membrane and cytolysis. The present study revealed that urea-EDTA solution is useful in extracting materials from porcine granulosa cells. The majority of the materials extracted from granulosa cells during the initial 30 min of incubation with urea-EDTA solution is considered to be from the cell surfaces and/or intercellular matrix.

Animals↗

Morphological changes of epiphyseal plate in the long bone of chondrodysplastic dwarfism in Japanese brown cattle.

A total of 20 cases of disproportionate calves on Japanese Brown cattle were examined morphologically. Investigation of 5 affected calves revealed that the insufficiency of endochondral ossification was confined only to the long bones of the limbs and was not accompanied by other associated changes. On the basis of the histological changes of epiphyseal plate and the affected site, this condition may be called chondrodysplasia of the rhizomelic type. Therefore, this disorder was defined as a bovine dwarfism. From three dimensional image analysis and histological changes of the tibial proximal portion in the other 15 cases, deformity and shortness of the tibia were related to the state of distribution and the degree of damages of the epiphyseal plate. In the affected cartilage matrix, cystoid degeneration, fibrous striation, bone spicule, necrotic foci and rent were found. Inadequate metachromasia suggests the abnormal staining of sulfated glycosaminoglycans and alcian blue stainability may be attributable to the abnormal interactions between proteoglycan and other matrix components. At the interface of cartilage and bone, irregular calcification, fibrotic scar and sealing by osseous tissue with relation to vascularity were found. These changes in this study indicated the failure of modeling on the epiphyseal plate, showing disturbance of chondrocytic differentiation and abnormal formation of the matrix.

Animals↗

Effect of estrogen on liver plasma membrane in rats.

The effect of estrogen on plasma membrane was investigated using the primary cultured rat hepatocytes treated with carbon tetrachloride (CCl4) and the isolated plasma membrane of rat liver. 17 beta-Estradiol (E2), at concentrations of 10(-10) M to 10(-4) M, 10(-8) M to 10(-6) M and 10(-12) M to 10(-4) M, had an inhibitory effect on the CCl4-induced leakage of glutamic oxaloacetic transaminase, glutamic pyruvic transaminase and lactate dehydrogenase, respectively from primary cultured rat hepatocytes. Diethylstilbestrol, which caused inhibition at a dose of 10(-4) M, did not inhibit any enzyme leakage at any further concentrations of 10(-12) M to 10(-6) M. In the isolated plasma membrane of rat liver, Mg(2+)- and Na+,K(+)-adenosine triphosphatase activity was increased by E2 treatment at concentrations of 10(-6) M and 10(-4) M.

Alanine Transaminase↗

A case of primary intrahepatic sclerosing cholangitis (PISC) complicated with atypical biliary epithelial proliferation.

A 70-yr-old woman was admitted to our hospital with duodenal ulcer and anemia. The result of liver function test was abnormal and showed persistent elevated alkaline phosphatase levels. Thus, after recovery from duodenal ulcer, endoscopic retrograde cholangiopancreatography (ERCP) was performed; the characteristic "beaded" appearance with band-like strictures and saccular outpouchings affecting the intrahepatic biliary system were found. The diagnosis of primary intrahepatic sclerosing cholangitis (PISC) was made on the basis of the generally accepted diagnostic criteria of primary sclerosing cholangitis (PSC). However, the histological finding from a liver biopsy specimen revealed highly atypical epithelial proliferation of bile ducts. This case of PISC complicated with atypical biliary glandular changes is described, and the distinction between PISC and carcinoma of the bile duct is discussed.

Aged↗

Effects of time-varying electromagnetic fields on K+ (Rb+) fluxes and surface charge of HeLa cells.

The magnetic flux density was varied intermittently from 0.35 to 1.77T and from 0.07 to 1.54 or 1.77T by manual and automatic switchings, respectively, of the power source of an electromagnet. The durations of the "switching-on time" and "-off time" were varied but kept equal. An electric eddy current induced in the culture medium by changes in the magnetic flux density was simulated. When the durations were shorter than 10s, ouabain-sensitive Rb+ influx (active K+ influx) into cultured HeLa cells was significantly inhibited, but the ouabain-insensitive Rb+ influx (passive K+ influx) was not influenced significantly. Inhibition of active Rb+ influx increased with time during exposure for 2 h. Conversely, K+ efflux from the cells was significantly stimulated by the exposure. Microfluorometric examinations of cells loaded with the fluorescent pH indicator 4-heptadecyl-7-hydroxycoumarin (6 microM) and the membrane potential indicator diS-C3-(5) (1 microM) suggested increase in the negative charge on the cell surface during exposure. The observed changes in the K+ (Rb+) fluxes would be related to change in the electric properties of the cell surface caused by exposure to intermittent electromagnetic fields.

Cell Membrane↗

[Cytogenetic analysis of lung tumors by in situ hybridization with chromosome-specific DNA probes].

Fluorescent in situ hybridization (FISH) with biotinated chromosome-specific repetitive DNA probes was used for the cytogenetic study of lung tumors and three cell lines of human lung cancer. The authors utilized a set of satellite DNA probes, specific for chromosomes 7, 17, X, Y in order to detect numerical chromosome aberrations in tumor cell nuclei. Normal diploid human lymphocyte nuclei, which served as the control, have have two signal spots in 95% of nuclei in response to 7, 17 chromosome probes. However, lung cancer cells have numerical heterogeneity, and copy numbers as determined by FISH were not definite with each probe. Discrepancies between cytogenetic and flow cytometric studies in the detection of aneuploidy in some tumors were shown. The number of FISH spots showed a correlation only with the Ki-67 labeling index expressed in proliferating cells. Loss of the Y chromosome in a high percentage of cells was seen by FISH in some tumors from male patients. These data indicate that FISH with chromosome-specific repetitive DNA probes can serve as a cytogenetic tool for the analysis of interphase nuclei of lung tumors with respect to the detection of numerical chromosome abnormalities.

Adult↗

[Randomized trial of cisplatin plus ifosfamide versus cisplatin plus vindesine for non-small cell lung cancer (NSCLC)].

Between 2/87 and 10/89, 83 patients (pts) with previously untreated NSCLC were assigned at random to receive either the PI regimen (cisplatin 80 mg/m2 dl and ifosfamide 2 g/m2 d 1, 2, 3, q 3-4 wks) or the PV regimen (cisplatin 80 mg/m2 d 1 and vindesine 3 mg/m2 d 1, 8, 15, q 3-4 wks). Three pts (2 PI regimen, 1 PV regimen) were ineligible for the study and 13 pts (7 PI regimen, 6 PV regimen) did not complete it. Thirty-three PI regimen pts and 34 PV regimen pts completed 2 or more cycles of the treatment and were evaluated. Patient characteristics were almost identical in both groups in terms of sex, age, pathological types, stage, performance status and number of chemotherapy cycles. For the PI regimen, there were 1 C.R. and 6 P.R., and the response rate was 21.2% (7/33). In the PV regimen, there were 11 P.R., and the response rate was 32.4% (11/34). The median survival time (MST) for PI regimen was 29 weeks (range 12-156 wks) and for PV regimen 40 weeks (range 8-138 wks). The difference in the survival curves for the 2 regimens was not statistically significant. Toxicities for the 2 regimens were similar except for greater leukopenia and one treatment-related death due to renal toxicity on PI regimen. These results suggest that PI regimen is not superior to PV regimen in the treatment of NSCLC.

Aged↗

[Clinical significance of oncogene product expression in human lung cancer].

The clinical importance of ras oncogene product p21 was evaluated in surgically treated non-small cell lung cancer patients. Paraffin sections of tumors were analysed immunohistochemically using anti-ras p21 monoclonal antibody rp35. The ras p21 expression was correlated with clinicopathological parameters and survival. Survival analysis demonstrated significantly longer survival times in patients with p21-negative tumors than those with p21-positive tumors. In Cox's multivariate analysis, ras p21 expression was a major and independent prognostic determinant of survival. On the other hand, in small cell lung cancer, L-myc gene is known to be frequently amplified and overexpressed. Immunoprecipitation analysis of two small cell lung cancer cell lines (classic type) revealed three major L-myc proteins (p60, p66 and p68), all of which were derived from extensive phosphorylation of a p59 protein. Expression and phosphorylation of L-myc protein, as well as the autocrine growth mechanism of gastrin-releasing peptide (GRP), is thought to be involved in the malignant behavior of small cell lung cancer.

Adenocarcinoma↗

Evidence of organ damage after cardiopulmonary bypass. The role of elastase and vasoactive mediators.

In this study the causes of organ damage after cardiopulmonary bypass were multifactorial. The concentration of the proteolytic enzyme elastase, which was released from activated granulocytes in the milieu of significantly reduced levels of alpha 1-protease inhibitor (p less than 0.01), increased during cardiopulmonary bypass (p less than 0.01). In addition, bypass initiated platelet aggregation, which both altered the eicosanoid metabolism and caused the level of thromboxane A2 to increase and surpass the level of prostaglandin I2. Because thromboxane A2 dominance subsided immediately after cardiopulmonary bypass, the effect of thromboxane A2 (vasoconstriction) on the development of organ damage may have been influential only during bypass. Both during and after bypass, the increase in endothelin excretion (p less than 0.01 to 0.05) was believed to induce a further vasoconstriction in the microvasculature. On completion of the cardiopulmonary bypass, the elevation of the lysosomal enzyme beta-glucuronidase, which is a sensitive indicator of cellular damage, was influenced by the concentrations of elastase (r = 0.8) and endothelin (r = 0.52). As evidenced by leuko-sequestration in the lung after cardiopulmonary bypass, the increase in the alveolar-arterial oxygen tension difference correlated with the elastase concentration (r = 0.68). Renal damage, which was detected by an increase in renal tubular enzymes (N-acetyl-beta-D-glucosaminidase and gamma-glutamyltranspeptidase) was affected by the endothelin (r = 0.68, 0.56) and elastase levels (r = 0.58, 0.68), respectively, but not by the ratio of thromboxane B2 to prostaglandin F1 alpha. The elastase level influenced the pulmonary vascular resistance (r = 0.56). However, neither the cardiac index nor the systemic and pulmonary vascular resistances were influenced by the endothelin level and the ratio of thromboxane B2 to prostaglandin F1 alpha.

Acetylglucosaminidase↗

[Bilateral pneumothorax and rupture of dissecting aortic aneurysm following a mitral valve replacement in Marfan syndrome: a case report].

A 12-year-old girl with Marfan syndrome was referred to our department because of severe mitral regurgitation. The patient was pale and in a pre-shock condition. The echocardiogram revealed a chordae rupture of the posteromedial papillary muscle at the posterior leaflet. A moderate dilatation of the aortic annulus (30 mm) and the ascending aorta (45 mm) without aortic regurgitation was also observed. Emergent mitral valve replacement was performed without replacement of the aortic valve or the ascending aorta. After two months, the patient developed bilateral pneumothorax, which was resistant to continuous suction therapy and finally required surgical treatments. Despite the relatively uneventful recovery, a lethal rupture of dissecting aortic aneurysm into the pericardial cavity, developed four months after the initial operation. We discussed the desired surgical approaches and respiratory problems in patients with connective tissue disorder.

Adolescent↗

[Breast conservation treatment of early breast cancer--eight-year experience].

In the period between 1983 and 1991, we experienced 80 cases of early breast cancer treated by conservative surgery and postoperative radiotherapy. Our indications for breast conservation treatment are the size of tumor (less than 2 cm), the location (more than 3 cm away from the nipple) and no palpable axillary nodes. Our surgical procedures of quadrantectomy and level I and II axillary dissection are presented. The shape of the skin incision should be elliptical with the major axis radial from the nipple for good cosmetic results. The entire quadrant of the breast containing the primary carcinoma is radically removed with the superficial pectoralis fascia. At present, one breast recurrence and two distant metastases have developed. A further follow up study is needed to prove the safety of breast conservation treatment.

Adult↗

[A clinical study of 115 patients with testicular tumor].

One hundred and fifteen cases of testicular tumors treated at our Hospital between 1970 and 1989 were analyzed. The incidence of testicular tumors was 0.44% in the male outpatient department of our urological clinic. The age of these patients ranged from 6 months to 86 years (average: 31.7 years old) with two peaks in distribution; 0 to 5 and 21 to 45 years. Most of their chief complaints (77%) were painless swelling of scrotal contents. Location of the tumors included 56 in the right, 57 in the left and 2 on both sides. Histologically, there were 68 cases of seminoma, 10 cases each of embryonal carcinoma and teratoma, 22 cases of mixed type, 3 cases of malignant lymphoma and 2 cases of others. Stage of tumor was stage I in 69 cases, IIA in 25 cases, IIB in 8 cases and III in 13 cases. High orchiectomy was performed on all the patients. Radiotherapy, chemotherapy and retroperitoneal lymph node dissection were respectively done in 77, 42 and 16 cases. Seventeen patients died, and the 5-year survival rate calculated by the Kaplan-Meier method was 87.9% in seminoma and 68.9% in non-seminoma. The survival rate for the patients treated by chemotherapy including CDDP after 1983 was compared to those treated by other therapy before 1982. Between the two groups there was no significant difference.

Adolescent↗

[Clinical studies on tosufloxacin (TFLX) in urology].

We clinically evaluated the usefulness of a new oral antimicrobial agent, TFLX, in the field of urology. The dose administered was 150 mg t.i.d and the duration of administration was 3 days. The clinical effect was evaluated according to the criteria of the Japanese UTI committee. The clinical response obtained on 164 female patients with acute simple cystitis was excellent in 118, moderate in 44 and poor in 2 patients. The efficacy rate was 98.78%. The clinical response obtained on 4 male patients with acute simple cystitis was excellent in 2 and moderate in 2 patients. The efficacy rate was 100%. The clinical response obtained on 3 female patients with simple pyelonephritis was excellent in 2 and moderate in 1 patient. The efficacy rate was 100%. The clinical response obtained on one patient with non-gonococcal urethritis was excellent by doctor's evaluation. The clinical response obtained on 7 patients with complicated UTI was excellent in 3 and moderate in 4 patients. The efficacy rate was 100%. Three patients complained of stomach distress or malaise and 2 patients developed rash. No abnormal laboratory data were observed. Thus, TFLX appears to be safe and suitable for use in the field of urology.

4-Quinolones↗