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Biomedical subjects

T Tamura

Publications and source records attributed to T Tamura.

At least 343 records · Page 19Linked to original sources

Accumulation of acid-fast lipochrome bodies in glial cells of the midbrain nigral lesion in Parkinson's disease.

To confirm or refute the proposed link between nocardiae and Parkinson's disease (PD), we investigated the presence of acid-fast spherical structures similar to filterable nocardiae at the midbrain nigral lesions of three patients with PD. Many clusters of acid-fast lipochrome bodies were dense around blood vessels in the two patients with Hoehn and Yahr stage II and III PD. These clusters were present in the vicinity of melanin-pigmented neurons in the three PD patients studied. Examination of adjacent hematoxylin-and-eosin-stained sections indicated that they consisted of yellow-green granules, bodies, and aggregates in ballooned glial cells. On the other hand, no clusters of acid-fast lipochrome bodies were observed at the compacta region of three control patients. Our results suggest that the immunological and genetic relationship between the acid-fast lipochrome bodies and filterable nocardiae should be investigated.

Aged↗

The 20S proteasome of Streptomyces coelicolor.

20S proteasomes were purified from Streptomyces coelicolor A3(2) and shown to be built from one alpha-type subunit (PrcA) and one beta-type subunit (PrcB). The enzyme displayed chymotrypsin-like activity on synthetic substrates and was sensitive to peptide aldehyde and peptide vinyl sulfone inhibitors and to the Streptomyces metabolite lactacystin. Characterization of the structural genes revealed an operon-like gene organization (prcBA) similar to Rhodococcus and Mycobacterium spp. and showed that the beta subunit is encoded with a 53-amino-acid propeptide which is removed during proteasome assembly. The upstream DNA region contains the conserved orf7 and an AAA ATPase gene (arc).

Acetylcysteine↗

Tyrosine phosphorylation of platelet derived growth factor beta receptors in coronary artery lesions: implications for vascular remodelling after directional coronary atherectomy and unstable angina pectoris.

BACKGROUND: Growth factors such as platelet derived growth factor (PDGF) have been postulated to be important mediators of neointimal proliferation observed in atherosclerotic plaques and restenotic lesions following coronary interventions. Binding of PDGF to its receptor results in intrinsic receptor tyrosine kinase activation and subsequent cellular migration, proliferation, and vascular contraction. AIMS: To investigate whether the concentration of PDGF beta receptor tyrosine phosphorylation obtained from directional coronary atherectomy (DCA) samples correlate with atherosclerotic plaque burden, the ability of diseased vessels to remodel, coronary risk factors, and clinical events. METHODS: DCA samples from 59 patients and 15 non-atherosclerotic left internal thoracic arteries (LITA) were analysed for PDGF beta receptor tyrosine phosphorylation content by receptor immunoprecipitation and antiphosphotyrosine western blot. The amount of PDGF beta receptor phosphorylation was analysed in relation to angiographic follow up data and clinical variables. RESULTS: PDGF beta receptor tyrosine phosphorylation in the 59 DCA samples was greater than in the 15 non-atherosclerotic LITA (mean (SD) 0.84 (0.67) v 0.17 (0.08) over a control standard, p < 0.0001). As evaluated by stepwise regression analysis, incorporation of both PDGF beta receptor tyrosine phosphorylation and immediate gain correlated strongly (adjusted r2 = 0.579) with late loss, although PDGF beta receptor tyramine phosphorylation alone correlated poorly with late loss. Multivariate regression analysis of coronary risk factors and clinical events revealed unstable angina as the most significant correlate of PDGF beta receptor tyrosine phosphorylation (F value 20.009, p < 0.0001). CONCLUSIONS: PDGF beta receptor tyrosine phosphorylation in atherosclerotic lesions is increased compared with non-atherosclerotic arterial tissues. The association of PDGF beta receptor tyrosine phosphorylation with immediate gain strongly correlates with vascular remodelling. PDGF beta receptor tyrosine phosphorylation correlates with unstable angina pectoris.

Angina, Unstable↗

Maladaptive remodeling of cardiac myocyte shape begins long before failure in hypertension.

Progression to failure in hypertension is associated with ventricular dilation, excessive myocyte lengthening, and an increase in myocyte length/width ratio. The temporal development of these changes in relation to impaired pump performance is unknown. We examined isolated myocytes from 1- to 12-month-old spontaneously hypertensive heart failure (SHHF) rats who develop heart failure at approximately 24 months of age. Left ventricular myocyte cross-sectional area reached a maximum of approximately 350 to 400 microm2 at 3 months of age and did not change significantly thereafter. Nonetheless, LV systolic wall stress, a known stimulus for myocyte transverse growth, increased progressively between 3 and 12 months of age. Unlike the situation in normally aging rats with stable body mass, myocyte length in SHHF rats continued to increase with aging (P<0.05 from 9 to 12 months of age). In summary, (1) left ventricular myocyte transverse growth reaches an upper limit by 3 months of age although systolic wall stress continues to rise; and (2) cell length is significantly increased by 12 months of age. This study suggests that maladaptive remodeling of cardiac myocyte shape begins long before pump failure in hypertension. Additionally, it appears that the left ventricle may be robbed of an important adaptive mechanism to normalize wall stress (eg, myocyte transverse growth) early in the progression to failure.

Aging↗

Phase III study of intensive weekly chemotherapy with recombinant human granulocyte colony-stimulating factor versus standard chemotherapy in extensive-disease small-cell lung cancer. The Japan Clinical Oncology Group.

PURPOSE: To evaluate the therapeutic significance of cisplatin, vincristine, doxorubicin, and etoposide (CODE) plus granulocyte colony-stimulating factor (G-CSF) compared with cyclophosphamide, doxorubicin, and vincristine, alternating with cisplatin and etoposide (CAV/PE) for extensive-disease (ED) small-cell lung cancer (SCLC). PATIENTS AND METHODS: Two hundred twenty-seven patients were randomized. CODE consisted of cisplatin 25 mg/m2 weekly for 9 weeks; vincristine 1 mg/m2 on weeks 1, 2, 4, and 6; and doxorubicin 40 mg/m2 and etoposide 80 mg/m2 for 3 days on weeks 1, 3, 5, 7, and 9. G-CSF 50 micrograms/m2 was administered on the days when chemotherapy was not administered. CAV/PE consisted of cyclophosphamide 800 mg/m2; doxorubicin 50 mg/m2; and vincristine 1.4 mg/m2 on day 1, which alternated every 3 weeks with cisplatin 80 mg/m2 on day 1 and etoposide 100 mg/m2 on days 1 to 3. RESULTS: Overall response rates were 77% for the CAV/PE arm and 84% for the CODE arm respectively (15% complete response in both arms). The median survival times were 10.9 months in the CAV/PE arm and 11.6 months in the CODE arm (P = .1034). The achieved dose-intensity for CODE was approximately twice that for CAV/PE for those drugs common to both arms. The incidence of leukopenia did not differ between the two arms, but anemia and thrombocytopenia had a significantly higher incidence in the CODE arm. Four treatment-related deaths from neutropenic fever occurred in the CODE arm. CONCLUSION: The CODE group had a similar median survival to the CAV/PE group. It does not appear that CODE is a useful approach to improve survival in ED SCLC.

Adult↗

Regulation of matrix metalloproteinases (MMP-2, -3, -9, and -13) by interleukin-1 and interleukin-6 in mouse calvaria: association of MMP induction with bone resorption.

Interleukin-1 (IL-1) greatly induces osteoclast formation and stimulates bone resorption of mouse calvaria in culture. In the presence of soluble IL-6 receptor (sIL-6R), IL-6 similarly induces osteoclast formation, but the potency of IL-6 in inducing bone resorption in organ culture is weaker than that of IL-1. To study the differences in bone-resorbing activity between IL-1 and IL-6, we examined the effects of the two cytokines on the induction of matrix metalloproteinases (MMPs). In mouse calvarial cultures, IL-1 markedly enhanced the messenger RNA (mRNA) expression of MMP-13 (collagenase 3), MMP-2 (gelatinase A), MMP-9 (gelatinase B), and MMP-3 (stromelysin 1), which associated with increases in bone matrix degradation. A hydroxamate inhibitor of MMPs significantly suppressed bone-resorbing activity induced by IL-1. Gelatin zymography showed that both pro- and active-forms of MMP-2 and MMP-9 were detected in the conditioned medium collected from calvarial cultures, and IL-1 markedly stimulated both pro- and active-forms of the two gelatinases. IL-6 with sIL-6R also stimulated mRNA expression and biological activities of these MMPs, but the potency was much weaker than that of IL-1. Conditioned medium collected from IL-1-treated calvariae degraded native type I collagen, but 3/4- and 1/4-length collagen fragments were not detected, suggesting that both collagenases and gelatinases synergistically degraded type I collagen into smaller fragments. In mouse osteoblastic cells, the expression ofMMP-2, MMP-3, and MMP-13 mRNAs could be detected, and they were markedly enhanced by IL-1alpha on days 2 and 5. IL-6 with sIL-6R also induced expression of MMP-13 and MMP-2 mRNAs on day 2, but the expression was rather transient. These results demonstrate that the potency of induction of MMPs by IL-1 and IL-6 is closely linked to the respective bone-resorbing activity, suggesting that MMP-dependent degradation of bone matrix plays a key role in bone resorption induced by these cytokines.

Animals↗

Inhibitory effect of cycloartenol ferulate, a component of rice bran, on tumor promotion in two-stage carcinogenesis in mouse skin.

Inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in mice was observed in the methanol extract of rice bran and gamma-oryzanol. The active components of rice bran, sitosterol ferulate, 24-methylcholesterol ferulate, cycloartenol ferulate and 24-methylenecycloartanol ferulate inhibited markedly the TPA-induced inflammation in mice. The 50% inhibitory dose of these compounds for TPA-induced inflammation was 0.2-0.3 mg/ear. Furthermore, cycloartenol ferulate markedly inhibited the tumor-promoting effect of TPA in 7,12-dimethylbenz[a]anthracene-initiated mice.

9,10-Dimethyl-1,2-benzanthracene↗

Two cases of hypertrophic cardiomyopathy with coronary vasospasm.

Chest pain in patients with hypertrophic cardiomyopathy seems to be caused by relative myocardial ischemia due to the left ventricular outflow pressure gradient and myocardial hypertrophy. However, in 2 cases of hypertrophic cardiomyopathy chest pain was associated with coronary vasospasm. Thus, chest pain in these cases was decreased not by a beta-blocker but by isosorbide dinitrate and a calcium antagonist. Because beta-blockers are commonly used for hypertrophic obstructive cardiomyopathy and chest pain may be aggravated by beta-blockers in patients with coronary vasospasm, a combination of beta-blocker, isosorbide dinitrate and calcium antagonist was necessary for this hypertrophic cardiomyopathy with variant angina.

Adrenergic beta-Antagonists↗

Gene cloning and characterization of an acidic xylanase from Acidobacterium capsulatum.

The gene xynA encoding an acid endo-beta-1,4-xylanase from an acidophilic bacterium, Acidobacterium capsulatum 161, was cloned and expressed in Eschrichia coli. The nucleotide sequence of the 1.6-kb DNA fragment containing xynA was analyzed, revealing an open reading frame of 1,215 bp encoding a peptide of 405 amino acid residues. The deduced amino acid sequence of XynA was very similar to other xylanases that are from the glycosyl hydrolase family 10. XynA was purified to homogeneity by SDS-polyacrylamide gel electrophoresis from E. coli transformants. The molecular mass and isoelectric point of XynA were 41 kDa and 7.3, respectively. The xylanase activity of the cloned XynA is an endo-acting enzyme that shows optimal activity at pH 5.0 and 65 degrees C, and is stable pH between 3.0 and 8.0. The K(m) and Vmax with oat spelt xylan as a substrate at pH 5.0 and 30 degrees C are 3.5 mg/ml and 403 mumol/min/mg.

Amino Acid Sequence↗

The mouse mammary tumor cell line, MMT060562, produces prostaglandin E2 and leukemia inhibitory factor and supports osteoclast formation in vitro via a stromal cell-dependent pathway.

Osteoclastic bone resorption increases at the site of bone metastasis, but little is known about how tumor cells induce osteoclast (OC) recruitment in the bone marrow microenvironment. To clarify this point, we examined the effects of various mouse tumor cells on OC recruitment using cocultures of tumor cells and mouse marrow cells. The mouse mammary tumor cell lines, MMT060562 (MMT), BALB/c-MC, Jyg-MC(A), or other nonmammary tumor cell lines, LLC and B16, were cocultured with mouse marrow cells, and OC recruitment from marrow cells was determined by counting the number of tartrate-resistant acid phosphatase-positive multinucleated cells (TRAP(+) MNCs) formed. Of the tumor cells examined, MMT and BALB/c-MC stimulated OC formation, but other tumor cells did not. OC formation with MMT was dependent on the number of MMTs inoculated, and only ten cells per well were sufficient to induce OC development. OCs appeared on day 4, and the number reached a maximum on days 5-8 and decreased thereafter. TRAP(+) MNCs induced by MMT satisfied the major criteria of OCs, such as the presence of calcitonin receptors and the ability to resorb calcified tissues. The majority of OCs were formed adjacent to the stromal cells, which were positive for alkaline phosphatase. When spleen cells were cocultured with MMT, no OCs were formed. In contrast, when osteoblastic cells were added to cocultures of spleen cells and MMT, many OCs were formed. The cultured media (CM) of MMT induced OC formation in mouse marrow cultures. Neither parathyroid hormone-like nor interleukin 1-like activity was present in the CM. MMT constitutively produced prostaglandin E2 (PGE2) and OC formation in cocultures was completely inhibited by indomethacin. Fractionation of the CM of MMT by ultrafiltration indicated that the OC-inducing activities were present not only in the fraction with molecular weight below 3 kDa but also in the fraction with molecular weight above 3 kDa. OC-inducing activity with high molecular weight was eluted around 50 kDa by Bio-Gel P-60 column chromatography. The active fractions also possessed leukemia inhibitory factor (LIF) activity, and OC-inducing activity of the peak fraction was inhibited in the presence of anti-LIF neutralizing antibody. The results of this study indicated that MMTs release PGE2 and LIF, which in turn stimulate OC formation via a stromal cell-dependent pathway. These culture systems will help to clarify the mechanisms by which tumor cells induce OC formation in a bone marrow microenvironment.

Acid Phosphatase↗

Effects of ageing and oestrogen on the localization of immunoglobulin-containing cells in the chicken ovary.

Immunoglobulins in the chicken ovary are important for transfer of immunity to chicks through the egg and for protection of the ovary from infection. The aim of this study was to examine the effects of ageing and oestrogen on the population of Ig-containing cells in the chicken ovary. The ovarian tissue of immature, young laying and old laying hens and that of immature birds treated with diethylstilboestrol (DES), progesterone or sesame oil (vehicle) was processed for paraffin wax sections. The sections were stained for IgG, IgM and IgA by an indirect immunostaining method and the population of cells positive for each Ig was analysed under a light microscope. The number of cells positive for IgG, IgM and IgA was significantly greater in the ovarian stromal tissue of young laying hens than in immature or old laying hens (P < 0.01). The number of IgG- and IgM-positive cells in the thecal layer of primary follicles of young laying hens was significantly greater than that in immature and old laying hens (P < 0.01) and there were significantly more (P < 0.05) IgA-positive cells in young laying hens than in immature birds. The number of IgG-, IgM- and IgA-positive cells was significantly (P < 0.01) greater in both the stromal tissue and the thecal layer of DES-treated birds than in the vehicle-treated birds. Progesterone had no significant effect (P < 0.05) on the population of Ig-positive cells. These results indicate that the number of Ig-positive cells increases as chickens mature and decreases with ageing, and that oestrogen may be involved in this process.

Aging↗

Effects of age and gonadal steroids on the localization of antigen-presenting cells, and T and B cells in the chicken oviduct.

The effects of age and gonadal steroids on the localization of immunocompetent cells, including antigen-presenting cells that contain the major histocompatibility complex (MHC) class II antigen, and T and B cells in the chicken oviduct were studied. Oviductal tissues were collected from laying and immature hens treated with diethylstilboestrol (an analogue of oestrogen) or progesterone. Cryostat sections of the tissues were immunostained for MHC class II, CD3 (T-cell antigen) and Bu-1 (immature B-cell antigen), and examined under a light microscope and an image analysis system. MHC class II+, CD3+ and Bu-1+ cells were observed in the mucosal epithelium and stromal connective tissue of both the laying and immature hens. MHC class II+ cells in the oviductal stroma appeared in association with oviductal development during sexual maturation and increased with ageing thereafter. The infiltration of CD3+ and Bu-1+ cells into the oviductal tissues increased in young laying hens compared with immature hens and decreased in old laying hens compared with young laying hens. Diethylstilboestrol increased the population of MHC class II+ and CD3+ cells in the stroma of the infundibulum and vagina, but had no significant effect on the population of Bu-1+ cells in the oviduct of immature hens. Progesterone increased the population of CD3+ cells in the stromal tissue of oviductal segments from all hens, and of Bu-1+ cells in the mucosal epithelium of the infundibulum and magnum, but had little effect on the frequency of MHC class II+ cells in the oviduct of immature hens. There were typically more immunocompetent cells in the infundibulum and vagina than in the other oviductal segments in laying hens and immature hens treated with sex steroids. These results suggest that local immunity in the chicken oviduct is enhanced during sexual maturation and possibly decreases during ageing. Gonadal steroids may play a significant role in the regulation of local immunity in the oviduct. The effects of oestrogen and progesterone on the influx of these immunocompetent cells into the oviduct differs among cell types and oviductal segments.

Aging↗

The effects of age and sex steroids on the macrophage population in the ovary of the chicken, Gallus domesticus.

The role of macrophages in the function of the hen ovary has not yet been described, although these cells may be an important regulator of ovarian function in mammals. The aim of this study was to determine the changes in the frequency of macrophages during ageing and follicular atresia, and the effects of sex steroids on the macrophage population in the hen ovary. Cryostat sections of ovarian tissues of immature, young laying and old laying hens and those of immature hens treated with or without diethylstilboestrol (DES) or progesterone were immunostained for macrophage cells using mouse anti-chicken macrophage monoclonal antibody. Macrophages were observed under a light microscope and counted using a computer assisted image analyser. The frequency of macrophages in both the stroma and theca of primary follicles was significantly greater in young laying hens than in immature and old laying hens and these cells were more frequent in old laying hens than in immature hens (P < 0.01). Macrophages were more frequent in atretic follicles than in normal follicles (P < 0.01). The number of macrophages in both the stroma and theca of primary follicles of DES-treated birds was significantly greater than in those of progesterone-treated and control birds (P < 0.01). Progesterone had no significant effect on the population of macrophages. These results suggest that macrophages in the ovary increase in association with sexual maturation of birds and atresia of follicles and decrease during ageing. Oestrogen may be one of the factors that affect the population of macrophages in the hen ovary.

Aging↗

Effect of rabeprazole (E3810), a novel proton pump inhibitor, on intragastric pH in healthy volunteers.

In this study, we examined the effect of rabeprazole (E3810), a novel proton pump inhibitor, on gastric acidity under physiological conditions in healthy volunteers using 24-hour intragastric pH monitoring. Twenty-four-hour intragastric pH monitoring was performed three times to seven subjects randomly assigned in a cross over fashion to one of the following groups; without drug administration (basal), and with 10 mg or 20 mg of rabeprazole for four days. The median pH for 24 hours was 2.15 in the basal study, while the corresponding median pH were 5.05 and 5.90 after treatment with 10 mg and 20 mg of rabeprazole, respectively. Significant differences in the median pH were observed between the basal study and that after administration of the 10 mg and 20 mg doses of rabeprazole. The cumulative percentage of pH readings above the threshold pH 4 value, was 34.1% in the basal study, and 72.6% and 78.3% after treatment with 10 mg and 20 mg doses of rabeprazole, respectively. This result indicates that the efficacy of rabeprazole allows for substantial control of gastric acidity with once-daily dosing, and that both the 10 mg and 20 mg doses result in potent inhibition of gastric acid secretion.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Effects of pH and osmolality on phlebitic potential of infusion solutions for peripheral parenteral nutrition.

In this study, we investigated the phlebitic potentials of several infusion solutions for peripheral parenteral nutrition to clarify the effects of pH and osmolality on the development of infusion phlebitis. A 10% glucose solution with electrolytes (GE, pH 4.93, 727 mOsm/kg), a 10% amino acid solution (AA, pH 6.95, 929 mOsm/kg), or a 5:2 admixture of GE and AA (GEAA, pH 6.46, 779 mOsm/kg) was infused into the rabbit ear vein for 6 hr at 10 mL/kg/hr, and the infused veins were examined histopathologically. Both GE and AA caused phlebitic changes, such as loss of venous endothelial cells, inflammatory cell infiltration, and perivascular edema. However, their admixture, GEAA, caused scant phlebitic changes. These results were as follows: 1) rabbit peripheral veins could tolerate the pH (6.46) and the osmolality (779 mOsm/kg) of GEAA under the conditions of this study; 2) GE caused phlebitis due to its acidity (pH 4.93); 3) AA caused phlebitis due to its hyperosmolality (929 mOsm/kg); and 4) mixing GE and AA eliminated the factors causing phlebitis in each solution. The admixture of GE and another 10% amino acid solution (AB, pH 6.04) at the ratio of 5:2 (GEAB, pH 5.76, 758 mOsm/kg) caused phlebitic changes. Since its osmolality was lower than that of GEAA, it was considered that GEAB caused phlebitic changes due to its acidity (pH 5.76), which was attributed to the acidic amino acid solution used as a component.

Amino Acids↗

Measurement of isolated myocyte volume using the Coulter models Z2 and ZM/C256: a comparison of instrument function.

Changes in cardiac structure that depart from normal have generally been termed "remodeling". Assessment of ventricular remodeling at the cellular level should include measurement of myocyte dimensions. A well-established and reliable method to assess myocyte remodeling uses isolated cells and the Coulter Counter/Channelyzer system. The new Coulter Model Z2 has numerous modifications and improvements from the Model Z predecessor(s) interfaced to a pulse-height analyzer (e.g., channelyzer). Improvements of the Model Z2 over older instruments include: (i) elimination of the mercury manometer with accompanying oil-displacement pump; (ii) reduced size and weight; (iii) a higher degree of mechanization and automation; (iv) inclusion of an advanced comprehensive statistical package and (v) a substantial reduction in cost. The purpose of this study was to determine if the newly modified instrument produces the same results as the previous instrument combinations, which were shown to produce reliable cell volume data from irregularly shaped cells such as cardiac myocytes.

Animals↗

Role of platelet-activating factor on extravascular lung water after coronary reperfusion in dogs.

Platelet-activating factor (PAF), one of the harmful substances released after coronary reperfusion, has been reported to increase pulmonary vascular permeability and induce pulmonary edema. In this study, we sought to examine the possible role of PAF in the genesis of pulmonary edema after coronary reperfusion. Extravascular lung water (EVLW) was measured by the thermal-dye double indicator dilution method during coronary ligation and after reperfusion in situ in dogs. The proximal left anterior descending coronary artery was occluded for 15 min and reperfused in 5 dogs (group 1), while five other dogs (group 2) were treated with PAF-antagonist (TCV-309, 1 mg/kg) before coronary artery occlusion. EVLW and hemodynamic indices were measured at baseline, 15 min of coronary occlusion, and 15 and 30 min after coronary reperfusion. EVLW increased at 15 min of coronary occlusion in both groups, but there was no significant difference between the two groups (6.4 to 10.3 ml/kg and 5.4 to 7.1 ml/kg in groups 1 and 2, respectively). After coronary reperfusion, EVLW increased further in group 1 (6.4 to 16.5 ml/kg, p < 0.01), but no further increase was observed in group 2 at 30 min after coronary reperfusion. There were no significant differences in hemodynamic indices between the two groups throughout the test. Thus, PAF-antagonist attenuated the increase in EVLW after coronary reperfusion independent of hemodynamic indices, and hence, PAF may play an important role in the genesis of pulmonary edema caused by coronary reperfusion.

Animals↗