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Biomedical subjects

H Takagi

Publications and source records attributed to H Takagi.

At least 199 records · Page 11Linked to original sources
PubMed1999

Prediction of cerebral infarct sizes by cerebral blood flow SPECT performed in the early acute stage.

Cerebral infarct due to embolic stroke without recanalization was examined by cerebral blood flow (CBF) SPECT in the early acute stage, and the possibility of predicting the size it will reach in the later stages was evaluated. Twenty patients (67 +/- 13 years) were examined by CBF SPECT with 99mTc-ECD 4.5 +/- 3.1 hours after the onset of cardiogenic cerebral embolism. The ratio of the anteroposterior length of the cerebral hemisphere to that of the severe ischemic region, which was defined as an area of clear-cut severe reduction in CBF as observed by SPECT, was calculated. One week after the onset, the cerebral infarct was measured in the same manner by CT, and the relationship between the two measurements was evaluated. The CBF in the region of severe ischemia and the surrounding region was determined by the Patlak plot method, and the affected/non-affected (A/NA) ratio was calculated. In severe ischemic regions the CBF ranged from 1.7 ml/100 g/min to 20 ml/100 g/min (mean, 11 +/- 5 ml/100 g/min), whereas the A/NA ratio ranged from 4% to 45% (mean, 26 +/- 11%). On the other hand, the CBF in the surrounding regions ranged from 20 ml/100 g/min to 52 ml/100 g/min (mean, 34 +/- 8 ml/100 g/min) whereas the A/NA ratio ranged from 52% to 104% (mean, 77 +/- 11%). The coefficient of correlation between the infarct size predicted by SPECT and that measured by CT was r = 0.986, and the correlation equation was Y = 1.047X - 2.969. CBF SPECT performed in the early acute stage can be used to predict the size of cerebral infarct.

Aged↗
PubMed1999

Mechanism of L-methionine overproduction by Escherichia coli: the replacement of Ser-54 by Asn in the MetJ protein causes the derepression of L-methionine biosynthetic enzymes.

We derived L-methionine-analogue-resistant mutants from Escherichia coli JM109 strain by mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine and selected the potent L-methionine-overproducing strains by microbioassay using lactic acid bacteria. One of the mutants, strain TN1, produced approximately 910 mg L-methionine/l following the addition of 0.1% yeast extract to fundamental medium containing glucose and ammonium sulfate. The L-methionine biosynthetic enzymes, cystathionine gamma-synthase and cystathionine beta-lyase, of the L-methionine-overproducing mutants were little repressed by L-methionine. To analyse the mechanism of L-methionine overproduction in the mutant strains, the metJ gene coding for the E. coli met repressor, MetJ protein, was cloned and sequenced by the polymerase chain reaction. The same single-amino-acid subsitution (wild-type Ser-->Asn) at position 54 was observed in four independent L-methionine-producing mutants. When the wild-type metJ gene was then introduced into strain TN1 having the mutant metJ gene, the level of enzyme synthesis and the L-methionine productivity in the transformants were found to revert to those of the wild-type. It was therefore considered that only one point mutation in the metJ gene occurred in the L-methionine-producing mutants. These results demonstrate the important role of residue 54 of the MetJ protein in L-methionine overproduction, probably because of the derepression of L-methionine biosynthetic enzymes.

Bacterial Proteins↗
PubMed1999

Nausea and vomiting induced by arterial chemo-embolization in patients with hepatocellular carcinoma and the antiemetic effect of ondansetron hydrochloride.

To determine the incidence of nausea and vomiting and the antiemetic effect of ondansetron hydrochloride (OND) in patients with hepatocellular carcinoma treated with arterial chemo-embolization, we studied 59 patients with hepatocellular carcinoma who were treated with transcatheter arterial embolization (TAE) or lipiodolized transcatheter arterial infusion (L-TAI). We investigated the incidence of nausea and vomiting and the amount of food intake when TAE or L-TAI was performed. All patients who experienced nausea and vomiting received OND administered prophylactically at the time of the next TAE or L-TAI to evaluate the antiemetic effect of the drug. Cumulative rates of nausea and vomiting during the week following arterial chemo-embolization were 44.8% and 27.6%, respectively. There was a tendency for the incidence to be higher in patients treated with the anticancer agent zinostatin stimalamer (SMANCS) than in those treated with epirubicin hydrochloride (EPI). Regarding food intake, 53.1% of the patients stated that they ate "half or more than half" of the food provided on the day of arterial chemo-embolization. The rate improved as time went on. In 5 patients who experienced nausea and vomiting at the time of arterial chemo-embolization, nausea and vomiting were inhibited satisfactorily by OND. When arterial chemo-embolization was performed, antiemetic treatment for approximately 3 days was necessary to improve patients' quality of life (QOL) to an acceptable level, and OND was found to be effective for the purpose in our 5 patients who had experienced nausea and/or vomiting at the previous treatment.

Adult↗
PubMed1999

Hypertension as a paraneoplastic syndrome in hepatocellular carcinoma.

We report a 66-year-old man with hepatocellular carcinoma who was positive for hepatitis B surface antigen, and was hospitalized because of hypoglycemia and hypertension. His plasma renin activity was normal (2.3 ng/ml per h), but concentrations of angiotensin I (>2500 pg/ml) and II (86 pg/ml) were high. Increased angiotensin I level at sites proximal and distal from the confluence of the hepatic vein and the inferior vena cava indicated that the hypertension was provoked by overproduction of angiotensin I from the hepatocellular carcinoma. Previous reports of patients with hepatocellular carcinoma with hypertension due to abnormality of renin-angiotensin system are reviewed.

Aged↗
PubMed1999

Expression of thrombospondin-1 in ischemia-induced retinal neovascularization.

Thrombospondin-1 is an extracellular matrix protein that inhibits endothelial cell proliferation, migration, and angiogenesis. This study was performed to investigate the role of thrombospondin-1 in ischemic retinal neovascularization. In a murine model of retinal neovascularization, thrombospondin-1 mRNA was increased from postnatal day 13 (P13), with a threefold peak response observed on P15, corresponding to the time of development of retinal neovascularization. Prominent expression of thrombospondin-1 was observed in neovascular cells, specifically, cells adjacent to the area of nonperfusion. It has been suggested that vascular endothelial growth factor (VEGF) plays a major role in ischemia-induced retinal neovascularization of this model, so we studied the effects of VEGF on thrombospondin-1 expression. In bovine retinal microcapillary endothelial cells, VEGF induced a biphasic response of thrombospondin-1 expression; VEGF decreased thrombospondin-1 mRNA 0.41-fold after 4 hours, whereas it increased, with a threefold peak response, after 24 hours. VEGF-induced endothelial cell proliferation was completely inhibited by exogenous thrombospondin-1 and increased by 37.5% with anti-thrombospondin-1 antibody. The present findings suggest that, in the ischemic retina, retinal neovascular cells increase thrombospondin-1 expression, and VEGF may stimulate endogenous thrombospondin-1 induction, which inhibits endothelial cell growth. VEGF-mediated thrombospondin-1 induction in ischemia-induced angiogenesis may be a negative feedback mechanism.

Animals↗
PubMed1999

Expression of secretory leukocyte protease inhibitor in women with endometriosis.

OBJECTIVE: To explore endometriosis-related molecules in patients with use of differential display analysis. DESIGN: Prospective study. SETTING: Nagoya City University Medical School, Nagoya, Japan. PATIENT(S): Women with endometriosis (n = 27) and without endometriosis (n = 21). INTERVENTION(S): Surgery was scheduled in the proliferative or secretory phase of the menstrual cycle. MAIN OUTCOME MEASURE(S): Differentially expressed products of endometrioma samples were sequenced at nucleotides. One of the candidate genes, secretory leukocyte protease inhibitor (SLPI) gene, was analyzed with use of in situ hybridization and Northern blot analyses. Distribution of SLPI was determined by immunohistochemistry, and the amount of SLPI in the peritoneal fluid and serum was measured by ELISA. RESULT(S): Distinct expression of SLPI messenger RNA could be detected in the endometrial-type epithelium of extrauterine endometriotic tissues and in the eutopic endometrium of women with endometriosis. SLPI was localized in the endometrial-type epithelium of endometriomas immunohistochemically. The amount of SLPI in the peritoneal fluid was markedly elevated in the endometriosis group (91.6+/-6.6 ng/mL compared with 68.4+/-5.3 ng/mL in the controls). CONCLUSION(S): Secretory leukocyte protease inhibitor may be involved in the pathogenesis of endometriosis.

Adult↗
PubMed1999

New surgical approach for removing massive foveal hard exudates in diabetic macular edema.

OBJECTIVE: To examine the efficacy of surgical removal of foveal hard exudates in diabetic macular edema and to determine the expression of vascular endothelial growth factor (VEGF) in the excised specimens. DESIGN: Cohort study. PARTICIPANTS: Seven eyes of six patients with massive subfoveal hard exudate due to diabetic macular edema were examined. The average age of the patient was 56 years (range, 46-60 years). INTERVENTION: Pars plana vitrectomy for removal of massive foveal exudates was performed. MAIN OUTCOME MEASURES: Preoperative and postoperative visual acuity and complications were recorded; immunohistochemical staining for VEGF and other cell markers for macrophage and pigment epithelial cells in excised specimens was performed. RESULTS: Postoperative best-corrected visual acuity improved by two or more lines of Snellen equivalent in five eyes (71%) (P = 0.0061). VEGF, identified by anticytokeratin and CD68 antibodies, was expressed in pigment epithelial cells and macrophages invading the hard exudates. CONCLUSION: Surgical removal of foveal hard exudates might be effective in low-vision patients with diabetic maculopathy. VEGF might play a role in the formation and persistence of foveal hard exudates in diabetic macular edema.

Cohort Studies↗
PubMed1999

HLA antigens in patients with interferon-alpha-induced autoimmune thyroid disorders in chronic hepatitis C.

BACKGROUND/AIMS: To determine the immunological predisposition to autoimmune thyroid disorders induced by interferon-alpha therapy, human leukocyte antigen (HLA) was analyzed in patients with chronic hepatitis C who developed autoimmune thyroid disorders during or after treatment with interferon-alpha. METHODS: Four hundred and thirty-nine patients with chronic hepatitis C (278 males and 161 females, aged 20-73 years) were treated with interferon-alpha (natural-alpha, 169; alpha-2a, 82; alpha-2b, 188) for 24 weeks. RESULTS: Seventeen of 439 (3.9%) patients developed symptomatic autoimmune thyroid disorders; these included nine cases of hyperthyroidism and eight cases of hypothyroidism. The incidence of HLA-A2, B46 and Cw7 increased in patients with interferon-alpha-induced autoimmune thyroid disorders. Especially, the incidence of HLA-A2 (15/17; 88.2%) was significantly higher than that observed in the general population in Japan (corrected p-value (p(c)): p(c)<0.003). The odds ratios for the relative risk of the autoimmune thyroid disorders were A2, 10.6 [95% confidence interval, 2.4-46.5]; B46, 4.8 [1.6-14.0]; and Cw7, 3.0 [1.1-7.9]. CONCLUSIONS: Our study revealed that HLA-A2 is highly linked to the autoimmune thyroid disorders induced by interferon-alpha-therapy in patients with chronic hepatitis C.

Adult↗
PubMed1999

Suppressive effects of josamycin on the development of altered liver cell foci and chronic nephropathy in a carcinogenicity study.

The carcinogenicity of josamycin was examined in Fischer 344 (F344) rats. Groups of 50 males and 50 females were given the compound in their diet at concentrations of 0 (control), 1.25 or 2.5% for 104-weeks; these dose levels were selected on the basis of the results of a subchronic study, in which animals rather rejected 5% josamycin. All surviving rats were killed at wk 106. A variety of tumours developed in all groups, including the control group, but all the neoplastic lesions were histologically similar to those known to occur spontaneously in this strain of rats, and no statistically significant increase in the incidence of any tumour was found in the treated groups of either sex. Interestingly, the josamycin treatment significantly reduced the development of altered liver cell foci and chronic nephropathy in a dose-dependent manner. Thus, it was concluded that, under the present experimental conditions, josamycin is not carcinogenic in F344 rats.

Animals↗
PubMed1999

Brain metastasis as first manifestation of ovarian cancer.

Brain metastasis from ovarian cancer, a rare and highly dismal event, develops mostly during or after postoperative chemotherapy. This report documents the clinical findings and magnetic resonance imaging of an uncommon case who presented signs of increased intracranial pressure as a first manifestation. Histologic examination of removed brain lesion demonstrated ovarian origin, while no evidence of a locally invasive lesion was found at exploratory laparotomy ('tentative' surgical stage Ia). The possibility of ovarian origin should be always considered in a woman with brain involvement.

Adult↗
PubMed1999

Tranilast inhibits protein kinase C-dependent signalling pathway linked to angiogenic activities and gene expression of retinal microcapillary endothelial cells.

1. Tranilast, first developed as an anti-allergic drug, has been reported to inhibit vascular endothelial growth factor (VEGF)-induced angiogenesis and vasopermeability. To further clarify the inhibitory mechanism, we investigated the effects of tranilast on VEGF binding and subsequent intracellular signalling pathway linked to angiogenic activities and gene expression of bovine retinal microcapillary endothelial cells. 2. Tranilast significantly (P<0.01) inhibited VEGF, basic fibroblast growth factor (bFGF), and hypoxia conditioned media-induced BREC proliferation in a dose dependent manner with IC50's of 22, 82 and 10 microM, respectively. 3. VEGF-induced migration was also inhibited by tranilast in a dose dependent manner, with IC50 of 18 microM, and complete inhibition was observed at 300 microM (P<0.01). Tranilast suppressed VEGF-induced tube formation in a dose dependent manner with maximum (46%) inhibition observed at 300 microM (P<0.05). 4. Tranilast inhibited phorbol myristate acetate (PMA)-dependent stimulation of [3H]-thymidine incorporation and VEGF- and PMA-induced gene expression of integrin alpha v and c-fos in BREC. 5. Tranilast suppressed VEGF- and PMA-stimulated PKC activity in BREC. 6. Tranilast did not affect VEGF binding or VEGF-induced phosphorylation of tyrosine residues of VEGF receptor- and phospholipase Cgamma and their associated proteins. 7. These data suggest that tranilast might prove an effective inhibitor to prevent retinal neovascularization in ischaemic retinal diseases, and that its inhibitory effect might be through suppression of PKC-dependent signal transduction in BREC.

Animals↗
PubMed1999

Evaluation of twice-daily administration of interferon-beta for chronic hepatitis C.

To improve the efficacy of interferon (IFN) in the treatment of chronic hepatitis C, administration of IFN-beta twice per day was evaluated. Thirty-eight patients with chronic hepatitis C (26 males and 12 females, aged 25-67 years) were included. Patients were treated with a new protocol that included twice-daily treatment with IFN-beta. Three million units (MU) of IFN-beta was administered twice daily every day for 4 weeks followed by 10 MU of IFN-alpha2b, every day for 2 weeks and then three times a week for 18 weeks (total IFN-beta, 148 MU; IFN-alpha2b, 680 MU). Complete responders (CR) were defined by alanine aminotransferase levels that normalized within 6 months after completion of IFN therapy and remained normal for more than 6 months, and by serum hepatitis C virus (HCV) RNA levels that became negative as determined using the Amplicor assay. Twenty-one of 38 (55.3%) patients were CR. Nine of 21 (42.9%) patients with HCV serotype 1 were responders compared with nine of 12 (75.0%) patients with HCV serotype 2. In patients with an HCV titre greater than 1 million equivalents ml-1 (1 MEq ml-1), nine of 24 (37.5%) responded, and in patients with HCV titres less than 1 MEq ml-1, 12 of 14 (85.7%) responded. In patients with HCV serotype 1 and greater than 1 MEq ml-1 HCV RNA, four of 15 (26.7%) responded to IFN. Two-thirds (66.7%) of the patients who became negative for HCV RNA after 2 weeks of therapy responded, while 72.7% of those with positive HCV RNA after 2 weeks of therapy were non-responders. Proteinuria was frequently observed as an adverse effect of twice-daily administration of IFN-beta. The combination of twice-daily administration of IFN-beta for 4 weeks followed by IFN-alpha showed a high response rate in patients with chronic hepatitis C, but in patients with both serotype 1 and a high titre of HCV RNA, response rates were still low. Thus, the HCV RNA titre 2 weeks after starting therapy with IFN was useful for predicting the eventual response to IFN.

Adult↗
PubMed1999

Expression of PRAD1/cyclin D1, retinoblastoma gene products, and Ki67 in parathyroid hyperplasia caused by chronic renal failure versus primary adenoma.

BACKGROUND: In primary hyperparathyroidism, certain genetic abnormalities responsible for parathyroid tumorigenesis are proposed, and it has been reported that the overexpression of PRAD1/cyclin D1 induced by a DNA rearrangement of the parathyroid hormone (PTH) gene is one of the genetic disorders in a number of primary parathyroid adenomas. However, in secondary hyperparathyroidism caused by uremia, the mechanism of monoclonal proliferation in nodular parathyroid hyperplasia is not well understood. To elucidate the mechanism, we examined the expression of PRAD1/cyclin D1, retinoblastoma gene products, and Ki67 in primary adenoma and secondary hyperplasia. METHODS: In adenomas (N = 15) and associated glands (N = 7) with normal histology obtained from patients with primary hyperparathyroidism and in diffuse (N = 14), multinodular (N = 58), and single nodular (N = 28) glands from patients who underwent parathyroidectomy for renal hyperparathyroidism, the expression of these cell cycle regulators was evaluated by immunohistochemical technique. A labeling index was used to define the proportion of cells with positive nuclear staining by each antibody. RESULTS: In 6 out of 15 (40%) primary adenomas, PRAD1/cyclin D1 was overexpressed (a labeling index of more than 500), possibly because of the PTH gene rearrangement, but not in secondary hyperplasia, including single nodular glands. Compared with diffuse hyperplasia, nodular hyperplasia showed a significantly higher expression of PRAD1/cyclin D1 (P < 0.05), retinoblastoma gene products (P < 0.05), and Ki67 (P < 0.05). However, no statistically significant correlation between the expression of PRAD1/cyclin D1 and that of Ki67 was observed in both primary adenoma and secondary hyperplasia. CONCLUSIONS: These results suggest that in secondary hyperplasia caused by uremia, at least remarkable overexpression of PRAD1/cyclin D1 induced by PTH gene rearrangement may be not the major genetic abnormality responsible for tumorigenesis. Heterogenous genetic changes seem to contribute to monoclonal proliferation of parathyroid cells induced by the expression of PRAD1/cyclin D1 or by some other mechanism independent of the amplification of the proto-oncogene.

Adenoma↗