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Biomedical subjects

M Yoshida

Publications and source records attributed to M Yoshida.

At least 847 records · Page 47Linked to original sources

Enhanced levels of oleate-dependent and Arf-dependent phospholipase D isoforms in experimental colon cancer.

Phospholipase D (PLD) (EC 3.1.4.4) is one of the intracellar signal transduction enzymes and plays an important role in a variety of cellular functions. In order to clarify the role of PLD in proliferation and tumorigenesis of colon cancer, we investigated the activities of oleate-dependent and ADP-ribosylation factor (Arf)-dependent types of PLD in experimental colon cancer of the rat. We produced colon cancer in Wistar rats by injecting the carcinogen, dimethylhydrazine dihydrochloride (DMH). The control rats were injected with physiological saline. Mucosal scrapings from the colon were homogenized and centrifuged to obtain the microsomal or membrane fraction. We measured the two types of PLD activities in these fractions using the transphosphatidylation reaction. Both oleate-dependent and Arf-dependent PLD activities were significantly higher in the colon cancer tissue than normal colonic mucosa. The mean specific activity of oleate-dependent PLD) in colon cancers was 1.66 +/- 0.75 (SD) nmol/min/mg whereas the value for normal colonic mucosa was 0.18 +/- 0.09 nmol/min/mg (P < 0.01; Mann-Whitney U-test). On the other hand, the mean specific activity of Arf-dependent PLD in colon cancers was 76.36 +/- 29.37 pmol/min/mg whereas the value for normal colonic mucosa was 19.90 +/- 11.97 pmol/min/mg (P < 0.01; Mann-Whitney U-test). These results suggest that PLD is implicated in the proliferation and tumorigenesis of colon cancer. The present study provides the first evidence for the enhanced levels of two types of PLD in colon cancer and raises the possibility that these PLDs can be used as the potential target for the treatment of colon cancer.

1,2-Dimethylhydrazine↗

Results of surgical treatment for thoracoabdominal aneurysm using cardiopulmonary bypass under moderate hypothermia and selective visceral artery perfusion.

From 1994 to 1997, 11 consecutive patients with thoracoabdominal aneurysms underwent surgery using cardiopulmonary bypass under moderate hypothermia (33 degrees C) and selective visceralartery perfusion for spinal cord and visceral organ protection. Distal perfusion pressure was maintained above 60 mmHg (mean) during cardiopulmonary bypass. In the four patients, one or two pairs of large intercostal arteries between Th10 and L2 were reimplanted. In the four patients, visceral and renal arteries were reconstructed. Surgical mortality rate within 1 month was 18.2% (2/11). One patient died of bleeding from old empyema and another of multiple organ failure. No patients had paraplegia. In conclusion, cardiopulmonary bypass with selective visceral artery perfusion under moderate hypothermia may contribute to the prevention of the occurrence of paraplegia and acute renal failure.

Aneurysm↗

Extra-anatomical bypass with EPTFE graft for residual pulmonary artery stenosis in Tetralogy of Fallot.

We describe the case of 35-year old woman who had undergone radical surgery to correct Tetralogy of Fallot malformation at the age of nine admitted to our hospital because of palpitation and exertional dyspnea. Angiography revealed 90% re-stenosis of the right pulmonary artery and grade IV tricuspid regurgitation. Right lung was perfused only 16.7% as shown by pulmonary perfusion scintigraphy. Interposition between the pulmonary trunk and right pulmonary artery using an EPTFE graft and tricuspid annuloplasty using a Duran ring was performed. Blood flow to the right lung improved markedly from 16.7% to 37.0% and her symptom disappeared completely.

Adult↗

[Structure and assembly of human beta herpesviruses].

This review is concerned with the structure and assembly of HCMV, HHV6 and HHV7. A characteristic ultrastructural feature common to all these viruses is a distinct tegumentary coating of intracytoplasmic capsids. The tegument structure is also distinctly seen in the virions of HHV6 and HHV7. Morphologically, acquisition of the tegument was observed to have taken place in the cytoplasm. Immunoelectron microscopic studies of HCMV infected cells, however, have demonstrated the existence of a tegument protein, pp150, on the surface of intranuclear capsids as well as on capsids in the cytoplasm and in extracellular virions. In addition, another tegument protein, pp65 has been detected within the matrix of cytoplasmic and extracellular dense bodies but not in virions. The molecular mechanism of the assembly of beta herpesviruses was also discussed.

Capsid↗

[A case of aneurysmal bone cyst arising from the left 4th rib].

We reported a case of aneurysmal bone cyst originating in the left 4th rib. This disease originating in a rib was recorded in only 18 cases in Japan in the literature. The patient was a 16-year-old man and he was first found to have an abnormal shadow in the left upper lung field on the chest roentgenogram. In this case, MRI was very useful to show internal septation of the tumor. We performed a thoracotomy through the left 4th intercostal space with an anteroaxillary skin incision and removed the tumor and the 4th rib completely. Pathological findings showed multiple cysts filled with blood and fibrous trabecullae containing osteoid tissue and multinucleated giant cells, confirming the diagnosis of aneurysmal bone cyst. There has been no evidence of recurrence during the 9 months postoperatively.

Adolescent↗

Overcoming drug resistance in lung cancer.

Anticancer drugs have been explored by means of random screening and demonstrated to be active against not only hematologic malignancies but also some solid tumors. Recent progress in the field of molecular biology has identified many new molecular targets for anticancer drugs. In this review, for example, signal-transduction pathways, which are influenced by newer agents like the taxanes (paclitaxel [Taxol] and docetaxel [Taxotere]) and the protein kinase C activator gnidimacrin, are evaluated. Efforts under way to integrate these new compounds into clinical trials are discussed.

Animals↗

[Phase I study of TAT-59 (a new antiestrogen) in breast cancer. TAT-59 Study Group].

Phase I study of TAT-59 (Miproxifen), an antiestrogen developed in Japan for breast cancer, was conducted with the collaboration of 12 hospitals. A single dose of 1.25, 5, 10, 20, 40 and 80 mg, or 5 consecutive daily doses of 1.25, 5, 10, 20 and 40 mg/day, were given orally. After single dosing, no clinical adverse effects were found. Decrease of serum Na, Cl, Ca level and increase of serum LDH level were observed in one patient after a single dose of 5 mg of TAT. An increase in the serum LDH level was also observed in one patient after a single dose in the of 10 mg of TAT. An increase in the serum LDH level and total bilirubin, increase of eosinophil, K and milky serum were also observed in one patient after a single dose of 40 mg of TAT, respectively. All of these abnormal values returned to the normal level within 26 days after final administration of TAT. No adverse clinical findings nor abnormal laboratory findings were observed after consecutive administration of TAT. After postprandial single dosing, the time to reach the maximum serum concentration (Tmax) of DP-TAT, dephosphorylated metabolite of TAT, and its demethylated metabolite, DMDP, ranged from 5.0 to 7.3 hr and from 17.0 to 42.8 hr, respectively. The maximum serum concentration (Cmax) and AUC of DP and DMDP elevated in a dose-dependent manner. T1/2 of DP and DMDP ranged from 24.2 to 41.5, and from 91.9 to 214.7 hr, respectively. There were no significant differences between pharmacokinetics of TAT before and after food intake. Based on the above results, we concluded that a Phase II study should be conducted to evaluate the efficacy, safety and optimal dose of TAT.

Administration, Oral↗

Upregulation of transforming growth factor-beta after panretinal photocoagulation.

PURPOSE: To determine whether upregulation of transforming growth factor-beta (TGF-beta) gene expression occurs after panretinal photocoagulation (PRP). To quantitate two TGF-beta isoforms in the aqueous and vitreous humors and to localize TGF-beta 2-like immunoreactivities (TGF-beta 2-LI) and TGF-beta 2 mRNA in the retina after PRP. METHODS: PRP was performed on Brown Norway rats by using an argon-green laser. Sensory retina, aqueous and vitreous humors were collected from the rats on days 1, 3, and 7 after PRP, and semiquantitative polymerase chain reaction analyses were carried out. TGF-beta 2 in the aqueous and vitreous humors was quantitated by enzyme-linked immunosorbent assay. Localization of TGF-beta 2-LI was demonstrated by immunohistochemistry, and that of TGF-beta 2 mRNA by in situ reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Gene expression of both TGF-beta 1 and -beta 2 was upregulated by PRP. Expression of TGF-beta 2 was greater than that of beta 1 (12.8-fold increase versus 3.24-fold increase, respectively, compared with control level on day 3). TGF-beta 2 concentration was increased in the vitreous humor (4.37-fold increase, P < 0.01) but not in the aqueous humor (the same level compared with control) on day 1. TGF-beta 2-LI and TGF-beta 2 mRNA were detected in cells of the outer retinal layer and in retinal pigment epithelial cells adjacent to the laser burns. CONCLUSIONS: PRP upregulates expression of TGF-beta 2 in the retina, and increased TGF-beta 2 concentrations are found in the retina and the vitreous humor. Retinal pigment epithelial cells and sensory retina around the laser burn appear to play a major role in the upregulation.

Animals↗

Prevalence and characterization of novel pANCA, antibodies to the high mobility group non-histone chromosomal proteins HMG1 and HMG2, in systemic rheumatic diseases.

OBJECTIVE: To determine the immunodiagnostic value of antibodies to the high mobility group non-histone chromosomal proteins HMG1 and HMG2, which have been identified as novel target antigens of perinuclear antineutrophil cytoplasmic antibodies (pANCA), in sera from patients with systemic rheumatic diseases. METHODS: Anti-HMG1 or HMG2 antibody was assayed by ELISA and Western blotting in sera from patients with systemic rheumatic diseases. These antibodies were analyzed for the relationship with pANCA detected by indirect immunofluorescence in these diseases, and with clinical features in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). RESULTS: Anti-HMG1 or HMG2 antibody was frequently detected in sera from patients with RA (48%), SLE (45%), Sjögren's syndrome (SS) (44%), and systemic sclerosis (SSc) (41%). In these diseases, anti-HMG1 antibody was detected more frequently than anti-HMG2 antibody. In sera from patients with RA, the positivity for anti-HMG1 and HMG2 antibodies was significantly correlated with the positivity for pANCA (p < 0.0001). Anti-HMG1/HMG2 antibodies were associated with some disease activity variables, e.g., erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, joint score and hand grip strength in RA, and CH50, C3, C4, and IgG in SLE. CONCLUSION: Anti-HMG1/HMG2 antibodies are detected commonly in systemic rheumatic diseases, particularly in RA, SLE, SS, and SSc. HMGI and HMG2 seem to be the significant target antigens of pANCA in RA. These antibodies are significantly associated with disease activity indices in RA and SLE.

Adolescent↗

Enhanced expression of a new class of liver-enriched b-Zip transcription factors, hepatocarcinogenesis-related transcription factor, in hepatocellular carcinomas of rats and humans.

Rat hepatocarcinogenesis-related transcription factor (HTF) was earlier identified as a b-Zip transcription factor in chemically induced rat hepatocellular carcinoma (HCC) by cDNA subtraction, and its structure was found to be different from that of the conventional b-Zip proteins. We investigated htf gene expression in rat tissues by Northern analysis and found that HTF expression was ubiquitous but was enriched in the liver. HTF expression increased concomitantly with HCC development in rat liver, and the HTF-containing DNA-binding factor also increased. Stimulated HTF gene expression also was observed in rat regenerating livers. From the results of various assays, X-box-binding protein 1/Tax-response element binding factor 5 was suggested to be a human homologue of rat HTF. In humans, HTF gene expression was also abundant in the liver and was revealed to be specifically stimulated in HCCs, but not in other types of cancers. To our knowledge, HTF is the first example of a liver-enriched transcription factor that exhibits HCC-associated gene expression. Injection of anti-HTF antibody decreased the growth rate of cultured HCC cells. Consequently, HTF is thought to participate in hepatocyte growth as well as in hepatocarcinogenesis.

Animals↗

Surgical results of composite graft replacement of the aortic root aneurysm.

From 1986 to 1996, 20 patients underwent aortic root replacement. All of the patients had annulo aortic ectasia (AAE); Six had DeBakey type I aortic dissection, three were acute dissections associated with Marfan's syndrome; three had previously undergone the Koster-Collins operation. During 11 years, the original Bentall procedure (1986-91), the Cabrol procedure (1991-), and the modified Bentall procedure (Carrel patch or Piehler technique) were performed. There was only 1 hospital mortality (5.0%). Four patients died during the follow-up period (mediastinitis, myocardial infarction, cerebral bleeding, and rupture of the arch aneurysm). Only 2 patients required reoperation (repair of a pseudoaneurysm of the right coronary artery and paravalvular leakage of the aortic valve replacement). The satisfactory outcomes were the result of the full-thickness anastomoses performed during coronary artery reconstruction.

Adult↗

[Retrospective analysis of elderly patients > or = 60 years of age with acute leukemia].

A retrospective analysis was performed on 76 consecutive elderly patients with acute leukemia aged 60 years or more (48 men, 28 women). Forty patients were 60-69 years old, 28 were 70-79 years old and 8 were > or = 80 years old. There were 55 patients with acute myelogenous leukemia (AML), 13 acute lymphoblastic leukemia (ALL) and 8 AML from myelodysplastic syndrome (MDS/AML). Patients were treated with the JALSG protocol, CAG regimen, or low-dose Ara-C regimen for AML, and DVP/M-CHOP protocol for ALL. The complete remission (CR) rates were 52.7% (29 of 55) in AML, 61.5% (8 of 13) in ALL, and 0% in MDS/AML. The median CR durations were 226, 85, 0 days, and the median survivals were 204, 177, 99 days, respectively. CR rates were 65.3% for the JALSG protocol, 62.5% for the CAG regimen and 25.0% for low-dose Ara-C regimen. According to age, CR was obtained 62.5% in patients aged 60-69 years and 33.3% in patients over 70 years old. Our results indicated that patients aged 60-69 years should be treated with intensive chemotherapy.

Aclarubicin↗

[Patho-MR imaging study in the putaminal margin in multiple system atrophy].

The slit hyperintensity of the lateral margin of the putamen in T2 weighted MRI is a characteristic finding in those patients with multiple system atrophy (MSA) involving extrapyramidal system. In spite of some speculations such as demyelination, gliosis, iron deposition or increased extracellular fluid, the nature of the abnormal signal intensity has still been remained uncertain. In this paper, we report the coincidental findings of pathology and magnetic resonance imaging of the putaminal margin in a case of MSA. The patient was sixty three years old woman with nine years history of intreatable parkinsonism, mild ataxia and dysautonomia. At six months prior to her death, 0.5T MRI showed the pontocerebellar system atrophy, slit hyperintensity in the bilateral outer margin and left inner margin of the putamen in T2 weighted image as well as linear hypointensity in T1 weighted image. The neuropathological examinations showed severe degeneration in the olivopontocerebellar and striatonigral systems, and glial cytoplasmic inclusion in widespread regions in the brain. The putamen showed severe degeneration with rarefaction. The intertissue space was observed at the outer putaminal margin in both sides and inner margin in left side, which seemed to be caused by severe shrinkage and rarefaction of the putamen. Thus, slit hyperintensity in the putaminal margin in MSA was disclosed to represent widened intertissue space.

Female↗

Characterization, localization and distribution of alpha1 adrenoceptor subtype in male rabbit urethra.

PURPOSE: The subtype specificity, localization and distribution of urethral alpha1-adrenoceptors were studied in the male rabbit urethra. MATERIALS AND METHODS: The properties of the urethral alpha1-adrenoceptors were investigated using radioligand receptor binding and light microscopic autoradiography with [125I]iodo-2-[b-(4-hydroxyphenyl)-ethylaminomethyl]tetralone (HEAT), and immunohistochemistry with monoclonal anti-alpha smooth muscle actin and anti-alpha sarcomeric actin antibodies. RESULTS: Saturation experiments with [125I]HEAT demonstrated the presence of significant amounts of a single high affinity binding site for alpha1 adrenoceptors in the male rabbit urethra. The pharmacological profile of the alpha1 adrenoceptors in rabbit urethra, determined by inhibition experiments with subtype selective alpha1 adrenoceptor antagonists, was characterized by the following rank order of potency of inhibition constants (Ki values): prazosin < or = WB 4101 < spiperone < 5-methylurapidil < BMY 7378. The pKi values for the rabbit urethra were correlated with the pKi values for rat spleen, submaxillary glands, and vas deferens and for those reported for cloned alpha1d receptors with correlation coefficients of 0.68, 0.929, 0.909, and 0.523, respectively. CONCLUSIONS: The pharmacological characterization demonstrates the predominance of alpha1A or alpha1A + alpha1B adrenoceptor subtype(s) in male rabbit urethral smooth muscle. Furthermore, the autoradiographic and immunohistochemical studies show a heterogeneous distribution of alpha1 adrenoceptors along the longitudinal axis of the urethra, within the smooth muscle fibers, with the receptors being localized more densely in the proximal than in the distal urethra.

Adrenergic alpha-1 Receptor Antagonists↗