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Biomedical subjects

H Takagi

Publications and source records attributed to H Takagi.

At least 469 records · Page 26Linked to original sources
PubMed1996

[In vitro direct antiproliferative activity and in vivo antitumor activity of bropirimine against bladder cancer].

Bropirimine is an antitumor agent currently used in clinical trials on bladder cancer. It is known to induce IFN, to activate NK cells and to inhibit the growth of tumor cells. In this study, we examined the in vitro and in vivo efficacy of bropirimine on human and murine bladder cancer. Bropirimine showed in vitro antiproliferative activity on the human bladder cancer cell lines, T 24 and KoTCC-1. This activity was not: affected by the neutralizing antibodies against IFN-alpha, TNF-alpha or IL-1 beta, indicating it is the direct activity of bropirimine without involvement of cytokine production by tumor cells. Bropirimine was active at the concentrations comparable to those in serum or urine attained in clinical trials, which suggests that this direct antiproliferative activity is one of the important antitumor mechanisms of bropirimine. In in vivo experiments, bropirimine reduced the growth of transplanted murine MBT-2 and human KoTCC-1 bladder cancers by oral administration every 4 days starting on day 1, but did not show efficacy when the drug treatment was started on day 8. The antitumor activity of bropirimine was dependent on the timing for drug treatment initiation.

Animals↗
PubMed1996

[A surgically treated case of ruptured true aortic arch aneurysm in association with Stanford type A chronic dissection].

A 72-year-old woman was admitted to our hospital because of hemosputum. Enhanced CT showed ruptured true aortic arch aneurysm. True aortic arch aneurysm ruptured at distal portion of aneurysm. The aorta was chronically dissected from an entry proximal to ruptured portion, to ascending aorta. Ascending aorta to aortic arch was replaced with 20 mm gelatin sealed graft under selective cerebral perfusion with hypothermia. Post-operatively tracheostomy was done because of respiratory failure, and there was some leak from distal anastomosis portion which was 42 mm in diameter at the operation. So replacement of descending thoracic aorta was performed using elephant trunk of the previously replaced graft. Post-reoperative course has been uneventful. She weaned from respiratory support. True aortic arch aneurysm combined with Stanford type A dissection is very rare. We presented ruptured true aortic arch aneurysm in association with Stanford type A chronic dissection which had an entry in true aneurysm.

Aged↗
PubMed1996

[Hepatocellular carcinoma following interferon therapy].

We experienced six patients with resected hepatocellular carcinoma (HCC) following interferon (IFN) therapy. Hepatitis virus C-RNA in polymerase chain reaction was positive in all patients prior to the IFN therapy. HCV-RNA became negative in two patients following IFN therapy, and was re-positive at the time of detection of HCC. In histological studies prior to the IFN therapy, pre-cirrhosis was diagnosed in four out of six patients and chronic active hepatitis 2B (CAH2B) in one according to the Europian classification. In non-cancerous portion of the liver, cirrhosis developed in five patients, and CAH2B in one. There was no significant correlation among the interval of HCC detection following IFN therapy, tumor size, tumor location, and histological findings. Patients should be carefully followed up by serum alpha fetoprotein levels or ultrasonography of the liver during and following IFN therapy.

Aged↗
PubMed1996

Hepatocellular carcinoma with pleural metastasis complicated by hemothorax.

Hemothorax can be caused by rupture of hepatocellular carcinoma (HCC). Hemoperitoneum is a well-known cause of death caused by rupture of a primary HCC lesion. Rupture of a HCC metastasis has not been adequately described. This is the first report of a HCC patient who died of hemothorax due to rupture of a pleural metastasis. The patient, a woman, died in respiratory failure 2 wk after rupture of her HCC metastasis in the pleura. Autopsy revealed moderately differentiated HCC in the liver, lung, and pleura. We discuss treatment options for ruptured pleura-based HCC metastases.

Adult↗
PubMed1996

Endothelin-1 action via endothelin receptors is a primary mechanism modulating retinal circulatory response to hyperoxia.

PURPOSE: To determine the role of endothelin (ET)-ETA receptor mediation and endogenous production of endothelin-1 (ET-1) in the retinal response to hyperoxia. METHODS: Brown-Norway rats (n = 30) were injected intravitreally with an ETA receptor-selective antagonist, BQ-123, and an inhibitor of ET-converting enzyme (ECE), phosphoramidon, and were exposed to a 100% oxygen breathing mixture. Control rats underwent intravitreal injection of vehicle alone (2.5% Emulphor in phosphate-buffered saline). The retinal hemodynamic responses were analyzed using video-based fluorescein angiography (VFA) methodology. Baseline measurements were made with the animals breathing room air, and this was followed by intravitreal injections of the above agents. Subsequent VFA measurements were made after 5, 10, and 15 minutes of breathing 100% oxygen. RESULTS: The 10 rats injected with vehicle alone demonstrated the expected retinal response to hyperoxia, with significant (P < 0.001) vessel constriction (18% +/- 5%), an increase in retinal mean circulation time (0.84 +/- 0.13 seconds in room air and 1.59 +/- 0.27 seconds in 100% oxygen), and a decrease in blood flow (110.7 +/- 19.2 pixel2/second in room air and 41.9 +/- 9.0 pixel2/second in 100% oxygen), compared to values measured during room air breathing. The hyperoxic response in rats (n = 9) injected with 10(-4) M BQ-123 was significantly (P < 0.001) blunted compared to the group injected with vehicle alone. In contrast, intravitreal injection of saralasin, a specific angiotensin II receptor antagonist, had no significant effect on the retinal response to hyperoxia (n = 5). Intravitreal phosphoramidon (10(-3) M, n = 6) injection also resulted in a significantly (P < 0.001) blunted circulatory response to hyperoxia compared to rats injected with vehicle alone. This blunted response after ECE inhibition was comparable to that measured after ETA receptor antagonism with BQ-123 injection. CONCLUSIONS: These results demonstrate that the enhancement of ET-1 action, possibly caused by the activation of ECE, plays a primary role in regulating the retinal hemodynamic response to hyperoxia.

Angiotensin Receptor Antagonists↗
PubMed1996

[Neoadjuvant chemotherapy in high-grade advanced gastric cancer with protracted infusional 5-fluorouracil and consecutive low-dose cisplatin].

Twenty-one evaluable patients with primary gastric cancer/local invasion, liver metastasis and peritoneal metastasis were entered in a pilot study of neoadjuvant chemotherapy that used continuous 24-hour infusion 5-FU, 330 mg/m2/day plus low dose CDDP, 6 mg/m2 daily by bolus infusion d1-5. This regimen was repeated for 4 weeks. The overall response rate was 52%, including one complete and ten partial responses. The response rate of differentiated adenocarcinomas was significantly higher than that of poorly differentiated adenocarcinomas. In 15 patients (71%), gastrectomy and lymphadenectomy could be done after this regimen. chemotherapy-induced downstaging from the initial clinical stage was pathologically found in 5 patients who underwent gastrectomy. Toxicity was primarily hematologic. Leukopenia and thrombocytopenia of grade 3 or 4 occurred in 19% and 14% of patients, respectively. The patients were able to take meals during therapy and preserved good quality of life. Median survival time was 11 months for the cancers with liver metastasis and five of the 8 locally advanced cancers are alive 11 months after the therapy. This therapy was effective for patients with high-grade advanced gastric cancer.

Adenocarcinoma↗
PubMed1996

Adenosine mediates hypoxic induction of vascular endothelial growth factor in retinal pericytes and endothelial cells.

PURPOSE: To determine the mechanistic role for adenosine and adenosine receptors in the hypoxic induction of vascular endothelial growth factor (VEGF) in retinal microvascular cells. METHODS: Bovine retinal capillary endothelial cells and microvascular pericytes were studied under normoxic (95% air, 5% CO2) or hypoxic conditions (0% to 2% O2, 5% CO2, 93% to 95% N2) using a variety of well-characterized adenosine and adenosine receptor agonists and antagonists. Vascular endothelial growth factor mRNA expression was evaluated by Northern blot analysis, VEGF protein levels were determined by Western blot analysis, and cyclic adenosine monophosphate (cAMP) accumulation was measured by radioimmunoassay. RESULTS: Inhibitors of oxidative respiration increased VEGF mRNA 5 +/- 3 times (P < 0.001) after 3 hours. Adenosine A1 receptor (A1R) agonist N6-cyclopentyl-adenosine did not increase VEGF mRNA at A1R stimulatory concentrations; however, adenosine A2 receptor (A2R) agonists DPMA, NECA, and CGS21680 increased VEGF mRNA in a dose-dependent manner with elevations of 2 +/- 0.3 (P < 0.001), 2.3 +/- 0.5 (P = 0.016), and 2 +/- 0.2 (P = 0.002) times, respectively. A2R antagonist CSC and adenosine degradation by adenosine deaminase reduced hypoxic stimulation of VEGF mRNA 68% +/- 18% (P = 0.038) and 37% +/- 6% (P = 0.025), respectively, in a dose-dependent manner. A1R antagonists DPCPX and 8-PT had no significant effect. Hypoxia and NECA increased VEGF protein secretion 4.7 times, whereas CSC inhibited hypoxia-induced VEGF protein secretion by 96%. NECA and CGS21680 increased cAMP production within 10 minutes, and cAMP stimulation increased VEGF mRNA 4.8 +/- 2.6 times (P = 0.034). CSC suppressed the hypoxic elevation of cAMP (P < 0.05). Inhibition of protein kinase A using H-89 reduced hypoxia-induced VEGF expression 61% +/- 6.3% (P = 0.043) in a dose-dependent manner. CONCLUSIONS: These data suggest that the hypoxia-induced accumulation of adenosine stimulates VEGF gene expression through stimulation of adenosine A2a receptor and subsequent activation of the cAMP-dependent protein kinase A pathway in retinal vascular cells.

Adenosine↗
PubMed1996

Morphological studies on Mn-SOD, NOS and calcium binding proteins in the rat hippocampus.

The immunohistochemical localization of manganese superoxide dismutase (Mn-SOD), nitric oxide synthase (NOS) and calcium (Ca) binding proteins; calbindin-D28K (Calb) and parvalbumin (Parv), was investigated in the rat hippocampus by using a double immunostaining method and an enzyme histochemical staining method. These substances showed considerable regional immunoreactivities in the hippocampus. (1) Although Mn-SOD- and NOS-immunoreactive neurons showed a similar distribution, virtually all of the latter neurons had no or weak Mn-SOD immunoreactivity in all subfields. This finding suggests that NO-producing neurons are not directly associated with Mn-SOD scavenger system in the hippocampus. (2) The co-localization of NOS and Parv or Calb was rarely found throught the hippocampus. (3) Neurons which were intensely immunostained for Mn-SOD were frequently found to be Parv-immunoreactive non-pyramidal cells, or Calb-immunoreactive pyramidal and non-pyramidal cells. From the latter two findings, it is speculated that Ca buffering effects of Parv and Calb are required in Mn-SOD neurons, but not in NO-producing neurons. Since Parv- or Calb-containing non-pyramidal cells are known to be GABAergic, most if not all, Mn-SOD-containing non-pyramidal cells may be GABAergic inhibitory neurons in the rat hippocampus. On the other hand, NOS neurons are also known to belong to GABAergic non-pyramidal cells. Therefore, Mn-SOD and NOS neurons constitute two distinct subclasses of non-pyramidal inhibitory neurons in the hippocampus.

Animals↗
PubMed1996

Regulation of retinal hemodynamics in diabetic rats by increased expression and action of endothelin-1.

PURPOSE: To investigate the role of endogenous endothelin-1 (ET-1) expression and its interaction with the ETA receptor in the physiologic regulation of vascular tone as well as in the development of abnormal retinal hemodynamics in diabetes. METHODS: Retinal blood flow, using digitized video fluorescein angiography recordings, was quantitated after intravitreous injections of ET-1; BQ-123, an ETA receptor antagonist; and phosporamindon, an endothelin converting enzyme inhibitor in the eyes of diabetic and nondiabetic rats. A total of 154 rats were used for these experiments. Message levels of preproendothelin-1 (preproET-1) were measured from the retina of diabetic and nondiabetic rats using competitive polymerase chain reaction (PCR) techniques. RESULTS: Retinal blood flow was reduced (33%, P < 0.001) in diabetic rats compared to nondiabetic rats. BQ-123, an ETA receptor antagonist, but not saralasin, an angiotensin receptor antagonist, increased retinal blood flow in a dose-dependent manner in diabetic (EC50 of 8 x 10(-7) M) and in nondiabetic rats (EC50 of 8 x 10(-8) M). Besides being resistant to BQ-123, the maximal response in diabetic animals occurred 20 minutes later than in nondiabetic animals. Decreasing ET-1 levels by inhibiting endothelin-converting enzyme with phosphoramidon normalized retinal blood flow in diabetic rats. In nondiabetic rats, the intravitreous injection of exogenous ET-1 (10(-8) M) resulted in retinal blood flow decreases comparable to those measured in diabetic animals, and the subsequent injection of 10(-4) M BQ-123 produced retinal blood flow changes comparable to those measured in BQ-123 injected diabetic rats. Comparison of preproET-1 messenger RNA expression in the retina, brain and lung of control and diabetic rats using quantitative PCR and Northern blot analysis showed 2.0- and 1.7-fold increases in the retina and the brain, respectively, without changes in the lung. CONCLUSIONS: These data suggest that ET-1 is involved in the regulation of retinal blood flow in normal physiologic outcome, and an increase in the endogenous expression of ET-1 contributes to the reduction of retinal blood flow reported in the early stages of diabetes mellitus.

Animals↗
PubMed1996

[A case report of multiple pseudoaneurysms of the left ventricle following acute myocardial infarction].

Multiple pseudoaneurysms of the left ventricle following acute myocardial infarction were successfully repaired in a 50-year-old man. Three days after onset of acute myocardial infarction, we electively performed PTCA on the right coronary artery which was completely occluded at the proximal segment. One month after PTCA, the left ventriculogram revealed multiple pseudoaneurysms of the left ventricle. Primary closure of orifices of the pseudoaneurysms was performed using pledgeted mattress sutures under cardiopulmonary bypass. Histology of aneurysm confirmed the diagnosis of pseudoaneurysm.

Aneurysm, False↗