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Biomedical subjects

M Takami

Publications and source records attributed to M Takami.

At least 73 records · Page 4Linked to original sources
PubMed1997

A novel thromboxane synthetase inhibitor, DP-1904, inhibits human blood eosinophil degranulation.

Eosinophils have been recognized to be associated with various immune responses and disease processes including bronchial asthma. Eosinophils release a number of cytotoxic and neurotoxic mediators. However, the factors regulating such release and the underlying mechanisms are unclear. In this study, we investigated the effect of a selective and potent thromboxane synthase inhibitor, DP-1904, on the release of eosinophil cationic protein (ECP) in platelet activating factor (PAF) and IgG-stimulated human blood eosinophils. PAF (1 microM) and IgG both released ECP which constituted about 25-30% of the total ECP content. The control protein, ovalbumin, did not release any ECP over the basal values. DP-1904 in two different concentrations, 10 microM and 100 microM, significantly attenuated the release of ECP in response to PAF or IgG. The mean percent inhibition by 10 microM DP-1904 was 49 +/- 10 and 31 +/- 2 against PAF and IgG-induced ECP release, respectively. However, at 100 microM DP-1904 the percent inhibition was 76 +/- 14 and 67 +/- 2, respectively. These data suggest that TXA2 is an important mediator in the regulation of eosinophil degranulation, and DP-1904 thus might prove beneficial in the treatment of bronchial asthma.

Asthma↗
PubMed1997

Breaks in double-strand DNA by Cu(II) complexes of etoposide (VP-16) and its derivatives, as evaluated by S1 nuclease treatment.

Single-strand breaks (ssb) in double-strand (ds) DNA produced by hydroxyl radicals (.OH) generated by Cu(II) complexes of podophyllotoxin (PD)-related compounds were evaluated using S1 nuclease digestion. Cu(II) complexes of VP-16 (etoposide, 4'-demethylepipodophyllotoxin-9-(4,6-O-ethylidene-beta-D-glucopyra noside)), 4'-demethylepi-PD (DEPD), and syringic acid (SA) exhibited both ssb and ds breaks (dsb) in ColE1-HaeII and pBR322-BglI DNA fragments, in which the number of ssb was found to be more than three times and four times greater than that of dsb, respectively. Cytosine (C)-methylation of cytosine-guanine doublet (CpG) in pBR322-BglI DNA inhibited both ssb and dsb within DNA segments by .OH generated by the Cu(II) complexes.

Antineoplastic Agents, Phytogenic↗
PubMed1997

[Preoperative synchronized chemoradiation therapy for advanced esophageal cancer].

Synchronized chemoradiation, where 5-FU and CDDP were synchronously administered in the same schedule with radiation therapy, was applied for advanced esophageal cancer in neoadjuvant fashion. Ten patients with advanced esophageal cancer were enrolled for this regimen consisting of 5-FU; 500 mg/day x 5/w x 4, CDDP; 10 mg/day x 5/w x 4 and radiation; 2 Gy x 5/w x 4. Tumor regression was achieved in all cases. In terms of toxicity, bone marrow suppression of more than grade 3 was observed in 60% of the cases, though it was safely controlled. Radical operation was performed on 8 cases. Histological responses in the resected specimen were as following: grade 3, 3 cases; grade 2b, 4 cases; grade 2a, 1 case; and 6 node-negative cases were found. As a postoperative complication, minor leakage occurred in 62.5%, while no major complications such as pneumonia were encountered. This neoadjuvant synchronized chemoradiation improved curability of the salvage operation and permitted reduction surgery for high-risk patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

[Local control of hepatic malignant tumors by percutaneous microwave].

We investigated the effects of percutaneous microwave coagulation under general anesthesia in the local control of hepatic malignant tumors. Coagulation at 60 W was done for normal liver of living swine using a percutaneous electrode. Wide-range coagulation at the tip of an electrode, 3 mm in diameter, was conducted. Clinically, echo-guided percutaneous microwave tumor coagulation was done for a total of 11 lesions in 5 patients with hepatocellular carcinoma and 4 with metastatic tumors in the liver under general anesthesia. Coagulation at 60 W of the liver of living swine for 1.5 and 10 min, using a percutaneous electrode, produced a maximal coagulation of 10, 20 and 30 mm, respectively. The trial electrode permitted coagulation almost at the tip of the electrode only. Percutaneous microwave coagulation of 11 lesions of the clinical cases resulted in complete coagulation in 7 lesions and incomplete coagulation in 4. The lesions showing complete coagulation were all less than 23 mm.

Animals↗
PubMed1997

[Complication of reservoir hepatic artery infusion chemotherapy and additional treatments].

In 54 patients who underwent hepatic artery infusion chemotherapy for hepatic tumors at our hospital between January 1990 and December 1996, we investigated the complications of this therapy and the therapeutic techniques following its discontinuation. The arterial infusion was discontinued in 36 of the 54 patients; 13 due to death (mean survival period: 15.7 months), and 23 in whom occlusion of the reservoir, etc. made it impossible to use arterial infusion (mean period of use: 13.8 months), and the minimum duration of use was 41 days and maximum duration of use 992 days. The most common complication of the reservoir hepatic artery infusion was reservoir occlusion (14.8%). Another serious complication was reservoir deviation outside the blood vessel in two patients; deviation in to the gastric lumen in one case and intraperitoneal deviation in the other. Four hepatocellular carcinoma patients, in whom it became impossible to use the reservoir due to its occlusion, underwent re-hepatectomy. Three of them survived for more than two years following supplemental local therapy, including subarterial injection, TAE, PEIT, microwave tumor coagulation (MTC). Of four patients with colon cancer metastasizing to the liver, one could undergo re-hepatectomy, one received subarterial injection, and two have survived without relapse. Two of three patients with breast cancer underwent systemic chemotherapy and endocrine therapy successfully, while the third one underwent subarterial injection and TAE, and is still under observation. Hepatic artery infusion should sometimes be discontinued owing to complications caused by various factors. Even if it becomes impossible to use the reservoir, local therapeutic techniques, including re-hepatectomy, TAE, PEIT, MTC, etc., may be performed in some patients. These findings suggest that it is necessary to review the interdisciplinary treatment so as to be appropriate to the primary disease.

Aged↗
PubMed1997

[Preoperative chemoradiation therapy for advanced rectal cancer].

Preoperative concurrent chemoradiation therapy with 5-fluorouracil and cisplatin was applied for advanced rectal cancer. Eligible criteria were as follows: no previous treatment, 4 more than hemicircular occupation, T3 or more invasion to adjacent organs or lymph node metastasis on CT scan, tumor fixation by digital examination. Eleven patients were enrolled with this regimen consisting of 5-FU; 500mg/day x5/w x4, CDDP; 10mg/day X 5/w x4 and radiation; 2Gy x 5/w x 4. As a toxicity, grade 2 leukopenia in 2 cases, grade 2 GI symptoms in one case and radiation dermatitis was observed in 8 cases. As a local response, there were PR in 10 cases and NC in 1 case. Surgical resection was performed on 8 patients. Histological responses in the resected specimens were grade 2, 5 cases; grade 1b, 1 case; and grade la, 2 cases. Operative radicalities were grade A, 3 cases; grade B, 3 cases; and grade C, 2 cases. Preoperative chemoradiation is one of the effective options in multimodal treatment for advanced rectal cancer.

Adenocarcinoma↗
PubMed1997

[Gene therapy by in vivo interferon-gamma gene transfer to murine bladder tumor].

For the clinical application of the cytokine gene therapy, the antitumor effects of systemic administration of Interferon-gamma (IFN-gamma) and those of in vivo direct IFN-gamma gene transfer to the tumors of mouse bladder carcinoma (MBT2) were compared. After the subcutaneous inoculation of MBT2 cells into mice, 10(2), 10(3) or 10(4) units of IFN-gamma were injected intraperitoneally (i.p.) or subcutaneously (s.c.). Neither i.p. nor s.c. injection of IFN-gamma resulted in tumor suppression or prolonged the survival time of tumor-bearing mice. The effect of in vivo direct IFN-gamma gene transfer by a retrovirus vector to MBT2 tumors was also evaluated. After the subcutaneous inoculation of MBT2 cells into mice, a virus culture supernatant containing IFN-gamma gene was injected into the same tumor site once a day for 3 days. In 50% of the mice in the treatment groups with IFN-gamma gene induction, no tumor formation was observed. Tumor-free survival and actuarial survival in the treatment groups were significantly longer than those in the control group. These results showed the possibility of in vivo direct IFN-gamma gene transfer into tumors and were encouraging for the execution of tumor cell-targeted IFN-gamma gene therapy against human bladder cancer.

Animals↗
PubMed1997

Functional evaluation of flail hip joint after periacetabular resection of the pelvis.

Five patients subjected to flail hip joint after resection of primary bone tumor of the pelvis involving acetabular region were examined with respect to function. When a thick portion of the supraacetabular pelvic neck was left in place, the operated legs functioned well regardless of whether the head of the femur was placed anterior or posterior to the iliac wing. In a patient who had only a thin portion of the iliac wing left in place and in those who underwent total excision of the ilium or hemiresection of the pelvis, the function of operated legs was poorer than with a thick portion of the supraacetabular pelvic neck left in place, but still more than 50% of leg function remained. Although flail hip joint results in a larger leg-length discrepancy than do other techniques, it enables favorable healing of the operative wound. Therefore, this method should be considered for women or sedentary patients with primary bone tumor of the pelvis involving acetabular region.

Acetabulum↗
PubMed1996

Adhesion through the interaction of lymphocyte function-associated antigen-1 with intracellular adhesion molecule-1 induces tyrosine phosphorylation of p130cas and its association with c-CrkII.

The B-lymphoblastoid cell line JY undergoes homotypic aggregation in a lymphocyte function-associated antigen-1 (LFA-1)-mediated, intracellular adhesion molecule-1 (ICAM-1)-dependent manner when stimulated with phorbol 12-myristate 13-acetate or anti-LFA-1 antibodies. Under conditions that lead to cell aggregation, we observed rapid tyrosine phosphorylation of p130cas, a protein previously identified to be phosphorylated on tyrosine in both v-src- and v-crk-transformed cells. Phosphorylation of p130cas was dependent on binding of LFA-1 to its ligand, ICAM-1, as demonstrated by the use of anti-ICAM-1 antibodies. Several observations suggest that this event may be an important step in the signaling pathway initiated by LFA-1. p130cas phosphorylation was rapidly reversible upon disengagement of the LFA-1-ICAM-1 complex and required cell adhesion since binding of phorbol 12-myristate 13-acetate-stimulated JY cells to purified ICAM-1 or cross-linking of either LFA-1 or ICAM-1 was not sufficient to induce phosphorylation of p130cas. The integrin-stimulated phosphorylation of p130cas created binding sites that were recognized in vitro by the SH2 domain of c-CrkII, a key adaptor protein involved in cell differentiation and transformation. Moreover, we also showed that the LFA-1-stimulated tyrosine phosphorylation of p130cas induces the formation of a p130cas.CrkII and p130cas.CrkL complex in intact cells. This observation suggests that adhesion mediated by the interaction of LFA-1 and ICAM-1 initiates a signaling cascade that involves the activation of protein tyrosine kinases and leads to the regulation of protein-protein interaction via SH2 domains, a key process shared with growth factor signaling pathways.

Antibodies↗
PubMed1996

Biodegradability of oxidized poly(vinyl alcohol).

Poly(vinyl alcohol) dehydrogenase (PVADH) purified from Pseudomonas sp. 113P3 catalyzed an oxidation of poly(vinyl alcohol) (PVA) in the presence of pyrroloquinoline quinone (PQQ) to give a beta-diketone structure on PVA. Although PVADH oxidized not only enzymatically oxidized PVA but also chemically oxidized PVA, PVA-degrading microorganisms, Pseudomonas sp. 113P3 and Arthrobacter tumescens sp. 52-1 grew on the enzymatically oxidized PVA, but not on the chemically oxidized PVA. This suggests that the growth of PVA-degrading microorganisms is affected by the structure of oxidized PVA.

Alcohol Oxidoreductases↗
PubMed1996

[Preoperative chemoradiation therapy for lower rectal cancer].

To identify appropriate candidates with rectal cancer for preoperative chemoradiation therapy, the local recurrence rate and clinicopathological characteristics of 232 patients with rectal cancer undergoing curative resection in our department were investigated. The local recurrence rates were 3.8%, 10.8% and 16.5% in the Rs, Ra and Rb lesions, respectively. Regarding lower (Rb) rectal cancer, depth of lesion (> a1) and nodal metastasis consisted of high factors for local recurrence. Basing on these results, entry criteria for preoperative chemoradiation therapy were established, and concurrent chemoradiation therapy with fluorouracil and cisplatin was delivered preoperatively in 9 primary cases of locally advanced rectal cancer and 3 cases with local recurrence. A partial response was obtained in 7 of 12 cases with a response rate of 58%, size-reduction of the distant metastatic lesions was found in 2 cases, and clinical symptoms were improved in all cases. The histological responses of the 6 resected cases were Grade 2 in 2 cases and Grade 1b in 4 cases. The toxicities of this chemoradiation regimen were well tolerable. As a postoperative complication, infection of the perineal wound was most frequent. Preoperative chemoradiation therapy with the present regimen would be a useful adjuvant treatment for advanced lower rectal cancer.

Aged↗
PubMed1996

[A case resectable hepatic metastases of breast cancer following intrahepatic arterial chemotherapy].

A 38-year-old woman who had undergone Patey's operation for left breast cancer in July 1990 was admitted in December 1992 for hepatic metastases. Due to bone metastasis (Th10), oophorectomy and hepatic arterial cannulation were performed. Hepatic arterial chemotherapy and oral chemoendocrine therapy yielded a partial response for liver and unclear metastasis of the bone. She had arterial and oral administration after a hepatectomy in October 1994. The patient has had no recurrent signs now (July 1996). We experienced 522 patients with breast carcinoma and 14 cases (2.7%) of all having hepatic metastases. Hepatic arterial chemotherapy was done in three patients. Although one of them had a complete response, she died after 35 months because of bone, brain and liver metastases. Another case was underwent hepatectomy after arterial chemotherapy, but recurrent liver and bone tumors soon appeared. The mean survival period of 15 hepatic metastases, including the case under study here was 9 months, and the one-year survival rate was 23.4%.

Adult↗
PubMed1996

[Evaluation of percutaneous microwave hepatic tumor coagulation therapy (PMTC) under general anesthesia from viewpoint of quality of life (QOL)].

We evaluated clinical benefits (QOL and local control rate) of percutaneous microwave coagulation therapy conducted with general anesthesia. Five cases with hepatic tumor (3 cases with hepatocellular carcinoma, 2 cases with metastatic hepatic tumor) were enrolled. The day following treatment all patients were virtually free of complaints with performance status ranging 0 to 1, and they were discharged from the hospital within 1 week. Four of five cases could be controlled solely with this treatment: one case showed local relapse, the tumor size of which exceeded 3 cm. PMTC may be one of the most beneficial local treatments for malignant hepatic tumor, since it shortens hospital stay with a good QOL status, and is applicable to metastatic tumor.

Aged↗
PubMed1996

[Effect of FUT-187, oral serine protease inhibitor, on inflammation in the gastric remnant].

Excessive enterogastric reflux following partial gastrectomy is believed to be responsible for the cause of inflammation in the gastric remnant. We examined the effect of FUT-187, a synthetic serine protease inhibitor, on symptoms and endoscopic findings in 33 patients who were diagnosed endoscopically as postgastrectomy gastritis. Patients took 50 mg FUT-187 orally after each meal and at bedtime for 8 weeks. Before treatment, 30 patients (91%) suffered from several symptoms including regurgitation and/or bitter taste in the mouth (49%), epigastric pain (42%) and nausea (36%). From endoscopic observation, erythema was detected in 32 patients, edema in 23 patients and erosion and/or ulcer in 9 patients. After treatment the global improvement rating for subjective symptoms was 76.7% (23/30) and the improvement of endoscopic findings was 63.6% (21/33). Diarrhea was observed in one patient but could be easily controlled by discontinuation of the drug. Our results suggest that FUT-187 can be a useful drug for the treatment of postgastrectomy gastritis with its efficacy and safety.

Administration, Oral↗
PubMed1995

Frequent loss of heterozygosity at telomeric loci on 22q in sporadic colorectal cancers.

To date, several tumor-suppressor genes responsible for the tumorigenesis of colorectal cancer have been identified. However, studies of loss of heterozygosity (LOH) have suggested several chromosomal regions which may contain additional tumor-suppressor genes for colorectal cancer. To determine the extent and variation of allelic loss on 22q, on which LOH has been frequently observed, a total of 68 sporadic colorectal cancers was examined for LOH on the chromosome arm by means of 16 polymorphic DNA markers. LOH was observed in 28 tumors (41%), of which 9 showed LOH at all informative loci. The remaining 19 tumors showed variable patterns of partial loss on 22q, delimiting the smallest region of overlap (SRO) between D22S90 and D22S94. Moreover, LOH within the SRO correlated with a progression in terms of Dukes' stages. These results suggest that an additional tumor-suppressor gene for colorectal cancer may exist on 22q distally to the NF2 locus and that inactivation of the gene may possibly play a role in the progression or metastasis of colorectal cancers.

Chromosome Deletion↗