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Biomedical subjects

T Nomiyama

Publications and source records attributed to T Nomiyama.

At least 37 records · Page 2Linked to original sources

Immunocytochemistry of fibronectin and endothelin-1 in the cavernous body of postnatal rabbit penises.

The differentiating cavernous body (CB) of postnatal rabbit penises was examined with a special reference to immunolocalizations for fibronectin (FN) and endothelin-1 (ET-1). At postnatal day 1, the CBs were embedded by an abundance of mesenchymal cells (MCs), and some of them were closely associated with endothelial cells of preexisting capillaries. Our electron micrographs indicated that such MCs are successively incorporated into the capillary endothelium as vasoformative cells. At this period, vascular sprouts of the helicine artery (HA), which were associated with the MCs, arose from the deep penile artery, and the transformation of such cells to endothelial and medial muscle ones was also indicated, and some MCs appeared to differentiate to epithelioid cells in the media. Immunoreactions for FN were preferentially localized in the rough endoplasmic reticulum (rER) and along the plasma membrane of such vasoformative MCs, and on the extracellular matrix components which connect these MCs with sprouts of both growing capillaries and HA. These findings suggest that FN, which is produced in the rER of the MCs, plays a crucial role in the mechanical linkage during the incorporation of vasoformative MCs into these penile vessels. Immunoreactions for ET-1 were preferentially localized on Weibel-Palade bodies in endothelial cells of the HA, implying the involvement of this peptide in the regulation of the local blood flow in this vessel.

Animals↗

A cross-sectional observation of the health effects of hydrazine hydrate and differences of its metabolism by NAT2 polymorphism.

OBJECTIVES: To summarize the results of two studies that attempted to clarify: (1) the health effects of hydrazine hydrate (HH) (N2H4 x H2O: CAS No. 7803-57-8); and (2) the influence of allelic polymorphism of N-acetyltransferase (NAT2) on the metabolism of HH. METHODS: A cross-sectional survey was carried out on 172 male HH-exposed workers and 125 male referent workers at five factories in Japan. The biological half-lives of HH after 1 h of exposure were determined in 12 workers, four workers in each of three NAT2 phenotypes. Clinical examinations were performed and acute and chronic subjective symptoms related to HH were examined by self-administered questionnaires. NAT2 phenotypes were assessed. RESULTS: No hydrazine was detected in either the breathing zones or the urine of the referent workers. The mean hydrazine concentration in the breathing zones, hydrazine and acetylhydrazine in urine, and the cumulative exposure level were 0.0109 ppm, 0.8660 micromol/g x Cr, and 2.80 ppm-years, respectively. There was no difference and no dose-dependent change in the health examination items between HH-exposed and referent workers after adjusting confounding factors, nor in terms of the differences of NAT2 phenotypes. Of 90 subjective symptoms, complaints of nightmares were significantly related to HH exposure. The half-life of urinary hydrazine and acetylhydrazine on rapid, intermediate, and slow phenotypes was 1.68, 3.01, and 4.46 h, respectively. CONCLUSION: This study suggested that current and cumulative exposure to HH did not affect the workers' health, and the half-life of the slow phenotype was longer than those of the rapid and intermediate phenotypes.

Adolescent↗

Evaluation of the subacute pulmonary and testicular inhalation toxicity of diborane in rats.

This study aimed to clarify the subacute pulmonary and testicular inhalation toxicity of diborane (B2H6, CAS: 19287-45-7) in rats. Male Wistar rats were exposed for 8 weeks to 0.11 or 0.96 ppm of diborane for 6 hr/day, 5 days/week. The control group was exposed to filtered air. Bronchoalveolar lavage fluid (BALF), hematological, biochemical, and histopathological examinations were conducted. Sperm counts and spermatic morphological changes were examined in epididymides, and histopathological examination was carries out in testes. BALF examinations revealed that the percentage of neutrophils increased in a dose-dependent manner and that of macrophages decreased in rats exposed to 0.96 ppm. Quantities of total and individual phospholipids in BALF increased in rats exposed to 0.96 ppm. The proportion of phosphatidylglycerol plus sphingomyelin decreased, and phosphatidylethanolamine and phosphatidylinositol increased in rats exposed to 0.96 ppm. LDH increased in rats exposed to 0.96 ppm, and ALP showed a dose-dependent increase. In serum, alpha 1-antitrypsin and superoxide dismutase activities increased in rats exposed to 0.11 or 0.96 ppm. These changes showed dose-dependent effects on the lung in rats exposed to diborane, possibly indicating that the hyperenergia of type II cells with proliferation and/or hypertrophy without histopathological changes occurred even in rats exposed to 0.11 ppm. Testicular examinations revealed no particular findings. The TLV-TWA of diborane (0.1 ppm) seems to be high and possibly unsafe, considering that the no-observed-effect level over 8 weeks for rat lung was under 0.11 ppm.

Administration, Inhalation↗

Changes in serum levels of metalloproteinases and their inhibitors by treatment of chronic hepatitis C with interferon.

We treated 18 patients with chronic hepatitis C by recombinant interferon-alpha (6 MIU for 24 weeks). In seven patients, serum aminotransferase levels declined to normal (responders). To evaluate the effect of interferon on matrix metalloproteinases (MMPs) and their inhibitors, namely tissue inhibitors of metalloproteinases (TIMPs), the serum levels of these enzymes were determined by enzyme immunoassay (EIA) using a specific monoclonal antibody. In responders, there was a tendency, but not a significant one, towards either an increase in serum MMP 1 levels or a decrease in serum TIMP 1 levels. In contrast, in nonresponders, both a significant decrease in MMP 1 and MMP 3 and a significant increase in TIMP 1 were observed. The number of cases of either increase in serum MMP levels or decreased in serum TIMP levels was significantly larger in responders than in nonresponders. Furthermore, the ratio of MMP 1 to TIMP 1 significantly increased in responders, suggesting that the balance between matrix formation and degradation in hepatic fibrosis tended to move toward degradation. These data indicate that interferon may exert a beneficial effect on hepatic fibrosis in parallel with improvement of aminotransferase activity.

Adult↗

Acute hepatitis in an adult with acquired rubella infection.

We report a case of acute hepatitis in a 28-year-old male with acquired rubella infection. Serological tests revealed acute rubella virus infection and ruled out infection by other common viruses, including type A and type B hepatitis viruses. The patient showed not only marked increase of lactate dehydrogenase (LDH) activity, with only slight liver dysfunction, but also platelet and kidney injury, suggesting systemic rubella virus infection. Because the liver dysfunction was slight, liver biopsy was not performed. When a patient has mild, transient hepatitis accompanied by high LDH activity in comparison with both aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, we should take a common viral infection such as rubella into consideration when making a diagnosis.

Acute Disease↗

Inhalation toxicity of diborane in rats assessed by bronchoalveolar lavage examination.

Changes in bronchoalveolar lavage fluid (BALF) and blood were examined to assess the toxic effects of diborane (B2H6, CAS: 19287-45-7) on the lung. Male Wistar rats were exposed to diborane at 20 ppm (intended concentration) for 4 h (phase I study) to evaluate time-course changes up to 14 days, and at 10 or 1 ppm (intended concentrations) to assess the dose-effect relationship after 3 days (phase II study). BALF parameters [leukocyte counts, alpha 1-antitrypsin (alpha 1-AT), superoxide dismutase (SOD), total protein, phospholipids etc.] were examined and biochemical and histopathological studies were also carried out. In the phase I study, neutrophils (%) in BALF increased on the day of exposure and then decreased gradually for 3 days. Rapid and marked increases in alpha 1-AT and SOD activity in BALF were detected on the day of exposure, and phospholipids had sharply increased on day 3. After 14 days, these parameters in the exposed rats had returned to their background level and alpha 1-AT decreased significantly. In the phase II study, total protein, alpha 1-AT activity and phospholipids in BALF showed dose-dependent increases, and serum alpha 1-AT activity increased significantly. Alveolar capillary and alveolar cell damage were confirmed in rats exposed to 20 ppm, 10 ppm or 1 ppm diborane for 4 h by evaluating the parameters examined. The protection system appeared to start operating immediately after exposure, and the recovery mechanism seemed to start operating 1 day after exposure and cease by day 14. The no-observed-effect level could not be observed.

Administration, Inhalation↗

No-observed-effect level of diborane on the respiratory organs of male mice in acute and subacute inhalation experiments.

In order to clarify the acute and subacute toxicity of diborane (B2H6, CAS: 19287-45-7) at low concentrations, male ICR mice were exposed to diborane for 1, 2, 4 or 8 h at concentrations of 1 or 5 ppm (phase I study), and for 6 h/day, 5 days/wk, over 2 or 4 wk at concentrations of 0.02 or 0.7 ppm (phase II study). Hematological and biochemical tests, and histopathological examinations of the cornea, nasal mucosa, respiratory tract and lung were carried out. All mice in both studies survived until they were sacrificed. In the phase I study, lung weight increased significantly in mice exposed to 5 ppm of diborane for 8 h. Histopathologically diffuse panbronchiolitis-like lesion was observed in mice exposed to 5 ppm of diborane for 2, 4 or 8 h. In the phase II study, slight infiltration of polymorphous neutrophil was observed mainly in the peribronchiolar region in mice exposed to 0.2 ppm or 0.7 ppm of diborane for 2 or 4 wk. In both studies, hematological and biochemical examinations failed to reveal any exposure-related changes. These results suggest that no-observed-effect level of diborane inhalation on the respiratory organs were 1 ppm in acute exposure, but 0.2 ppm of diborane inhalation for 2 or 4 wk seems to be unsafe.

Acute Disease↗

Pharmacokinetics of the gastrokinetic agent mosapride citrate after single and multiple oral administrations in healthy subjects.

The pharmacokinetics and dose proportionality of mosapride citrate ((+-)-4-amino-5-chloro-2-ethoxy-N-[[4- (4-fluorobenzyl)-2-morpholinyl]methyl]benzamide citrate dihydrate, AS-4370, CAS 112885-42-4) were investigated in healthy male volunteers. The subjects were given a single oral dose (5, 10, 20 and 40 mg, each of 5 subjects) and a multiple oral dose (20 mg t.i.d. for one day, and 10 and 20 mg t.i.d. for 8 days, each of 5 subjects). Food effect on the pharmacokinetics of mosapride was also evaluated after a single oral 10 mg dose by an open, two-way crossover method. Mean plasma levels of mosapride reached a peak 0.5-1 h after single dosing of 5, 10, 20 and 40 mg. The peaks were dose-related with values of 25.1, 51.2, 157.8 and 280.6 ng/ml, respectively, and were followed by a first-order decrease with apparent half-lives of 1.4-2.0 h. The Cmax and AUC increased in proportion to the dose, indicating linear pharmacokinetics of mosapride up to 40 mg. The Cmax of M-1, a des-4-fluorobenzyl metabolite, was 1/6 of that of the unchanged drug. Urinary excretion of the unchanged mosapride and M-1 during 48 h after single dosing accounted for 0.1-0.4% and 7.0-11.0% of the dose, respectively. There were no significant changes in the plasma concentration-time profiles and urinary excretions between single and multiple doses, indicating that the pharmacokinetics of mosapride in man was not altered by its multiple administration. Plasma levels of mosapride reached steady state on day 2 of multiple administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Combination chemotherapy for a senile patient with adenoid cystic carcinoma of the esophagus: a case report.

Adenoid cystic carcinoma of the esophagus with multiple liver metastases was found in a 77-year-old Japanese female in October, 1991. Combination chemotherapy, including etoposide (VP-16) and tegafur (FT) allowed the patient to survive for approximately a year after the onset of the initial symptoms. During her course of treatment, the patient improved greatly with minimal toxicity, and declines in the elevated levels of GOT and LDH were also noted. Since no other therapy, such as surgery or radiation, was given to the patient, the response to chemotherapy as well as the survival advantage for the patient have been evaluated.

Aged↗

[Intraocular barrier permeability in spontaneously diabetic Chinese hamster].

Fluorophotometry was performed with normal and spontaneously diabetic Chinese hamsters (CHAD) in order to investigate differences in blood-ocular barrier permeability and lens autofluorescence. Blood-aqueous barrier permeability was evaluated by the fluorescence value in the anterior chamber which was corrected using both autofluorescence value and the concentration of fluorescein in the plasma. The results showed that the diabetic group had significantly higher values than the normal group (p less than 0.01). Blood-retinal barrier permeability was evaluated in the vitreous by the same method. There was no significant difference between the two groups. Lens autofluorescence values were also significantly higher for the diabetic group compared with the normal group (p less than 0.001). In these spontaneously diabetic Chinese hamsters, the permeability function of the blood-retinal barrier seemed to be maintained its normal level, while both the blood-aqueous barrier and lens were damaged by deleterious effects of diabetes.

Animals↗

Hyperplastic cellular components of a hemangiopericytoma. An ultrastructural study.

Based on ultrastructural features of cellular components of a hemangiopericytoma, hyperplastic cells are classifiable into fibroblast-like (group I), endotheloid (group II) and pericyte-like (group III) cells. The transformation of the group I cells to the group II, or to the group III cells, is pronounced in our electron micrographs and this may imply that the group I cell is the principal cell of origin in this neoplasm. The smooth muscle-like (group IV) cells comprising the media of the arteries and veins in this neoplasm may represent modified, possibly de-differentiated smooth muscle cells reacted to the neoplastic proliferation of the surrounding adventitial (group I) cells.

Adult↗

Neovascularization in the pre- and postnatal rabbit corpora cavernosa penis: light and electron microscopy and autoradiography.

In the late prenatal stage, the rabbit corpora cavernosa penis (cavernous bodies) are occupied by a large number of mesenchymal cells actively proliferating by mitosis. Most profiles of the cavernous sinuses show growing capillaries consisting of immature endothelial cells and enclosing a narrow lumen. Such growing capillaries are often associated with the mesenchymal cells that contact with each other and eventually with the endothelial cells. Between 1 and 7 postnatal days, the capillary network develops extensively and the maturation of the capillaries results in a flattened endothelium with a continuous basal lamina. The mesenchymal cells are also associated with the helicine arterial sprouts at this time period. No endothelial mitotic figures were observed within the growing capillaries in pre- and postnatal specimens examined. Single pulse labeling with 3H-thymidine in the postnatal rabbits demonstrates that the labeled endothelial cells of the growing capillaries increase in number at 48 hours after injection compared with those at 24 hours, whereas the labeled mesenchymal cells inversely decrease in number. These findings indicate that the incorporation of the mesenchymal cells as vessel-forming cells into the growing capillaries accelerates the neovascularization in the rabbit cavernous bodies.

Animals↗

Histamine disposition in endothelial specific granules of the toad aorta.

High-performance liquid chromatography revealed that toad aorta delivered appreciable concentrations of histamine into the perfusate when perfused by Ringer's solution containing the histamine liberator. Electron micrographs of this vessel after the perfusion showed an expulsion of the endothelial specific granules into the vascular lumen. These results support to our previous hypothesis that the granules are a reservoir site of histamine and might take an important role in the regulation of vascular tone.

Animals↗