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Biomedical subjects

T Ishikawa

Publications and source records attributed to T Ishikawa.

At least 361 records · Page 20Linked to original sources

Mice deficient in the nucleotide excision repair gene XPA have elevated sensitivity to benzo[a]pyrene induction of lung tumors.

This study is focused on chemical induction of lung tumors in xeroderma pigmentosum group A gene (XPA)-deficient mice to clarify the role of nucleotide excision repair (NER) in internal organs. Six-week-old female XPA-/-, XPA(+/-) and XPA(+/+) mice were instilled intratracheally with benzo[a] pyrene (B[a]P). A total of 68 surviving XPA mice treated with B[a]P were examined at month 16. The pulmonary adenoma incidence in XPA(-/-) mice was significantly higher than that in XPA(+/+) mice (71 versus 35%). Similarly, tumor multiplicity was elevated and, in addition, only XPA(-/-) mice had lung carcinomas. These results provide the first evidence that a deficiency in the NER gene XPA leads to enhanced tumorigenesis in the lung after exposure to B[a]P.

Animals↗

Study on eight patients with malignant tumors after renal transplantation.

The high incidence of cancer after renal transplantation is now a critical concern since the graft survival rate has been improved extensively. We experienced 9 malignancies in 8 patients out of 168 recipients up to December 31, 1999 in our hospital, consisting of a case of gastric plasmacytoma and cases of cancer in the liver (2), thyroid (2), prostate (1), breast (1), sigmoid colon (1) and gall-bladder (1). Two patients were diagnosed as having tumors within 3 months after transplantation, suggesting post-transplant acceleration of growth of the latent tumors. The other patients were diagnosed at an average of 128 months, ranging from 84 to 263 months after transplant. Two patients died of gastro-intestinal bleeding and acute heart failure. Four patients died directly of progressive neoplasm within 3 months after diagnosis. These results suggest that the course of malignancies developing in post-transplant recipients is more aggressive than that expected in non-transplant patients, and it is very important to intensively follow long-term surviving cases to detect the malignant tumors as early as possible.

Adolescent↗

Reliable differential diagnosis between osteosarcoma and regenerative bone cells in rats through simultaneous analysis of nuclear DNA content and size.

OBJECTIVE: To evaluate the difference between benign proliferative lesions of regenerative bone calluses and malignant tumors in rats by simultaneous analysis of nuclear DNA content and size. STUDY DESIGN: Nuclei were stained with DAPI and measured by cytofluorometry. Five regenerative bones and five osteosarcoma samples were used. Two-dimensional dispersion diagrams between relative nuclear DNA content and nuclear size were drawn up and their regression lines were compared. RESULTS: It was possible to distinguish between osteosarcomas and regenerative bones by simultaneous analysis of nuclear size and DNA content during the cell cycle. The results yielded coefficients of correlation and regression. All five regression lines of osteosarcomas were situated dramatically higher on dispersiongrams than those of regenerative bones. CONCLUSION: Differential diagnosis between regenerative lesions and malignant tumors may now be possible using simultaneous measurement of nuclear DNA content and size.

Animals↗

[A case of metastatic colon carcinoma in which a continuous intrahepatic artery-infusion of 5-FU leucovorin and cisplatin, and systemic chemotherapy with CPT-11 was very effective].

We report a patient with metastatic colon carcinoma who was treated effectively with a continuous intrahepatic artery-infusion of 5-FU, Leucovorin and cisplatin, and systemic chemotherapy with CPT-11. A 50-year-old man was diagnosed as having well differentiated adenocarcinoma of the sigmoid colon with multiple liver metastases in March, 1997. Left hemicolectomy and subsequent catheterization into the common hepatic artery via the gastroduodenal artery were performed in April, 1997. He was treated with 3 courses of continuous intrahepatic artery-infusion of 5-FU, Leucovorin and cisplatin, and two courses of systemic chemotherapy with CPT-11 during hospitalization, followed by 6 courses of a similar intraarterial therapy in an outpatient setting. Reinstallation of the catheter into the hepatic artery via the femoral artery was performed because of occlusion of the reservoir. During the 6th course of intraarterial therapy, diarrhea, nausea, and vomiting appeared and angiography revealed a narrowing of the hepatic artery. Therefore, the intrahepatic artery-infusion therapy was reinitiated with doses of 5-FU, Leucovorin and cisplatin reduced to approximately 80%. After 5 courses of this therapy, the computed tomography scan showed a marked decrease in the size of the metastatic hepatic lesions by 90%, and the serum level of CEA decreased from 657.7 ng/ml to 4.5 ng/ml. No severe side effects were seen during the treatment. Though multiple lung metastases were indicated during the intrahepatic artery-infusion therapy, both the liver and lung metastases have been well controlled with continuous intrahepatic artery-infusion chemotherapy and systemic chemotherapy. The continuous intrahepatic arterial infusion of 5-FU, leucovorin and cisplatin appears to be very effective for the treatment of colon carcinoma with liver metastasis without reducing the quality of life.

Adenocarcinoma↗

[Asystole during electroconvulsive therapy in a patient with depression and myasthenia gravis].

A 44-yr-old woman presented with major depression. She was scheduled to receive electroconvulsive therapy under anesthetic care because of drug-induced leukopenia. Her significant past medical history was myasthenia gravis. She had been treated with thymectomy and pyridostigmine. She showed no evidence of muscle weakness while receiving the medication. After preanesthetic assessment, pyridostigmine was continued and routine anesthetics were chosen. Under 100% oxygen inhalation, thiamylal and suxamethonium were administered intravenously. Alternate current was delivered for 5 seconds, which induced seizure satisfactorily. However, asystole lasted for 10 seconds during the procedure. Spontaneous beating appeared followed by tachycardia and bigemina. Normal sinus rhythm returned four minutes later. She recovered smoothly, and showed no evidence of confusion nor muscle weakness. We speculated that pyridostigmine potentiated the ECT-induced vagal reflex and provoked asystole. In the following session, we pretreated her with intravenous atropine prior to thiamylal and suxamethonium. Although the current delivery increased RR-interval up to 1.2 seconds, neither asystole nor serious tachyarrhythmia occurred. Seven sessions of ECT relieved her psychiatric symptoms uneventfully. We presented a case of depression for which ECT was applied. Asystole with ECT seems associated with administration of pyridostigmine for the treatment of myasthenia gravis. Pretreatment with atropine can prevent asystole without inducing hazardous tachyarrhythmia.

Adult↗

[Recurrent pulmonary embolism from left subclavian thrombosis: a case report].

A 38-year-old woman was admitted to our hospital because of pulmonary thromboembolism. Thrombolysis therapy resulted in initial improvement in symptoms and laboratory data. However, 4 months later, pulmonary thromboembolism recurred despite antiplatelet and anticoagulation therapy. Contrast venography and venous ultrasonography of both upper and lower extremities revealed subtotal occlusion and venous thrombosis of the left subclavian vein with collateral vessels, but no evidence of lower extremity venous thrombosis. She had no history of subclavian venous catheterization, neoplasm, hypercoagulability or other predisposing cause of thrombus formation. Operative ligation of the left subclavian vein was performed at the junction with the internal jugular vein. White thrombus was identified within the venous lumen. She was well without recurrent pulmonary thromboembolism or venous insufficiency for 10 months after the operation. Surgical interruption of the subclavian vein may be effective to prevent recurrent pulmonary thromboembolism in patients with recurrent pulmonary thromboembolism due to venous thrombosis of the upper extremity despite therapeutic anticoagulation.

Adult↗

Evaluation of serum KL-6, a mucin-like glycoprotein, as a tumor marker for breast cancer.

The utility of serum KL-6 as a tumor marker for breast cancer was evaluated in this study. The sera from 146 patients with breast cancer, 13 with benign breast disease, and 108 healthy individuals were measured for KL-6 titer using a sandwich enzyme immunoassay method. Carcinoembryonic antigen (CEA) and carbohydrate antigen 15-3 (CA15-3) titers were also tested in the same sera from the patients. The mean KL-6 titer of patients with primary breast cancer was 673 units/ml, which was significantly higher than that of benign and healthy individuals (P = 0.037 and P < 0.0001, respectively). The titer of patients with relapsed breast cancer was 1964 units/ml, which was also higher than that of primary cancer (P = 0.013). KL-6 titer was related to tumor stage, distant metastasis, and relapse site (P = 0.0053, P < 0.0001, and P = 0.0251, respectively). Using the cutoff value of 467 units/ml, the sensitivity of KL-6 was 31% for primary breast cancer (16% for stage I and 29% for stage II) and 73% for relapsed breast cancer (50% for local relapse and 89% for distant relapse). The specificity was 92%. The sensitivity of KL-6 was higher than that of CA15-3 and CEA. Combination of the three markers, followed by KL-6 and CEA, raised the sensitivity for primary breast cancer. Single use of KL-6 demonstrated a higher sensitivity than in each combination for relapsed breast cancer. In conclusion, serum KL-6 may be helpful for clinical use as a tumor marker for breast cancer, and it may play an important role, especially in the surveillance of disease relapse.

Adolescent↗

[Improvement in the regimen for combined CDDP and CPT-11 chemotherapy].

UNLABELLED: Combination therapy with cisplatin (CDDP) and irinotecan hydrochloride (CPT-11) is expected to be effective against refractory tumors. The antitumor effect of CPT-11 is believed to depend on the area under the concentration-time curve (AUC) of SN 38, which is a metabolite of the prodrug CPT-11. Of the major adverse effects of CPT-11, leukopenia is dependent on the AUC of CPT-11 and severe diarrhea is believed to be dependent on the peak concentration (Cmax) of SN 38. Considering these properties of CPT-11, we investigated the administration of a new regimen. METHOD: The subjects were patients with gynecological cancer who consented to intra-arterial [IA] infusion. The patients received CDDP (30 mg/m2 over 2 hours) concurrently with CPT-11 (40 mg/m2 over 24 hours) at 2-week intervals. Plasma concentrations of platinum and CPT-11 were measured before and after administration. To prevent binding of SN 38 to the large intestinal mucosa, we performed 1) alkalization, 2) detoxification of SN 38, and 3) clearance of the large intestine. RESULT: 1) A decrease in tumor diameter or negative conversion on cytology and reduced tumor marker levels were observed in patients receiving IA infusion. 2) No serious adverse reactions occurred, except grade 3 diarrhea in one patient given infusion at the initial dose. 3) The rate of conversion from CPT-11 to SN 38 was about 10%, which was higher than the 3% rate after standard 90-minute intra-venous [i.v.] infusion. 4) In the patients treated with IA infusion, CPT-11 levels in venous blood were one thirty-third of those in arterial blood. 5) Regarding the venous blood concentration of platinum when CDDP (30 mg/m2) was administered, the AUC of free platinum in patients given IA infusion was about 2.5 times that after i.v. infusion. CONCLUSION: The IA infusion treatment produced a good clinical response with good compliance.

Adenocarcinoma↗

[Expandable metallic stent for the treatment of left-sided colonic obstruction with malignant disease].

Recently, it was reported that an EMS (expandable metallic stent) was useful for treatment of colorectal obstruction. In our department, EMSs were used for seven patients with left-sided colonic obstruction with unresectable malignant disease. After these treatments with EMS, their symptoms were improved and they were able to intake food. Stomal formation was avoided except in one patient with severe soiling. In conclusion, EMS is thought to be useful for the improvement of quality of life in the patients with unresectable malignant colonic obstruction.

Adult↗

[Three cases of metastatic breast cancer, resistant to pre-chemo and/or endocrine therapy, markedly improved with UFT and cyclophosphamide oral combination therapy].

The cases of 3 female patients with metastatic breast cancer treated with oral UFT and cyclophosphamide (CPA) are reported. Patient 1 had lymph node and bone metastases. Patient 2 had bone metastasis. Patient 3 had skin, lymph node, and peritoneal metastases. All had a history of mastectomy and chemo- and/or endocrine therapy for metastatic lesions. Patients 2 and 3 had also undergone CAF combination chemotherapy. However, the lesions did not change. UFT 400 mg and CPA 100 mg, everyday, were administered to patient 1. UFT 400 mg and CPA 100 mg, 2 weeks, and UFT 400 mg, 2 weeks, were given every 4 weeks to patient 2. UFT 300 mg and CPA 150 mg, 6 weeks per 8 weeks were given to patient 3. Improvements in the metastatic lesions were seen 4 weeks after the beginning of UFT and CPA therapy. Therapy is now continuing, and no patients had a progression of the disease. All had leukopenia 2 or 4 weeks after the beginning of this therapy, and two temporarily stopped the therapy. No other side-effect was observed. Oral UFT and CPA combination therapy was considered useful for metastatic breast cancer. To prevent leukopenia and prolong the term of treatment efficacy, a treatment regimen will need to be established.

Administration, Oral↗

[A case of panpleuropneumonectomy for diffuse pleural mesothelioma].

A 58-year-old man was admitted to our hospital because of chest pain and dyspnea on July 15, 1999. A chest X-ray showed left pleural effusion, and a chest CT revealed left pleural effusion and diffuse pleural thickening. Because pleural fluid cytology and percutaneous needle pleural biopsy were negative for malignancy, thoracoscopic biopsy was performed on July 28. The biopsied specimen revealed malignant pleural mesothelioma (epithelial type). An operation was performed on August 16. First, mediastinal lymph node dissection was performed and we identified that there was no lymph node metastasis by frozen section diagnosis. Then panpleuropneumonectomy with combined resection of the diaphragm and pericardium was performed.

Diaphragm↗

Ileosigmoid anastomosis with exclusion of transected ileal loop for intestinal fistula following total cystectomy of bladder cancer. Report of a case.

We report in this article a new technique of surgical treatment of enterocutaneous or enterovaginal fistula after total cystectomy for three cases of bladder cancer. The surgical outcome was successful in these patients, showing good performance status after this operation. It would seem that this technique is a good indication for enteric fistulas in the bottom of the pelvic cavity, which were difficult to be managed even under the control of total parenteral nutrition.

Abscess↗

Effects of aldehyde dehydrogenase and acetyl-CoA synthetase on acetate formation in sake mash.

To reveal the mechanism of the production of acetate by sake yeast (Saccharomyces cerevisiae), the expression of genes encoding aldehyde dehydrogenase (ALD), acetyl-CoA synthetase (ACS) and acetyl-CoA hydrolase (ACH), which are related to acetate production, was investigated. Northern blot analysis using total RNA of sake yeast isolated from sake mash revealed that all of the tested genes, ACS1, ACS2, ALD2/3, ALD4, ALD6 and ACH1, were transcribed during sake fermentation. Transcription of ALD2/3 was detected only in the early stage of sake fermentation. A static culture of sake yeast in hyperosmotic media including 1 M sorbitol or 20% glucose resulted in high acetate production and increased transcription of ALD2/3. This is the same result as reported in an aerobic condition, and induction of ALD2/3 seemed to be one reason for high acetate production at high glucose concentration during fermentation. Overexpression of ACS2 resulted in low acetate production both during small-scale sake fermentation and in a static liquid culture. On the other hand, over-expression of ACS1 did not change acetate productivity significantly in a static culture. These results indicate that ALD2/3 and ACS2 play important roles for acetate production during sake fermentation.

Journal Article↗

Inhibitory effect of tea flavonoids on the ability of cells to oxidize low density lipoprotein.

Dietary flavonoid intake has been reported to be inversely related to mortality from coronary heart disease, and the anti-atherosclerotic effect of flavonoids is considered to be due probably to their antioxidant properties. Oxidation of low density lipoprotein (LDL) has been reported to be induced by the constituent cells of the arterial wall. Accordingly, we examined the effect of pretreatment with tea flavonoids, such as theaflavin digallate, on the ability of cells to oxidize LDL. Theaflavin digallate pretreatment of macrophages or endothelial cells reduced cell-mediated LDL oxidation in a concentration- (0-400 microM) and time- (0-4 hr) dependent manner. This inhibitory effect of flavonoids on cell-mediated LDL oxidation was in the order of theaflavin digallate > theaflavin > or = epigallocatechin gallate > epigallocatechin > gallic acid. Further, we investigated the mechanisms by which flavonoids inhibited cell-mediated LDL oxidation using macrophages and theaflavin digallate. Theaflavin digallate pretreatment decreased superoxide production of macrophages and chelated iron ions significantly. These results suggest that tea flavonoids attenuate the ability of the cell to oxidize LDL, probably by reducing superoxide production in cells and chelating iron ions.

Animals↗

Endothelium-dependent flow-mediated vasodilation in the postprandial state in type 2 diabetes mellitus.

This study examined the effects of fat- plus sucrose-rich meals on endothelium-dependent flow-mediated vasodilation in diabetic patients. Flow-mediated vasodilation in the postprandial state decreased significantly, and the decrease correlated inversely with the magnitude of postprandial hyperglycemia, suggesting that endothelial function in diabetic patients becomes impaired postprandially.

Adult↗

Intestinal polyposis in mice with a dominant stable mutation of the beta-catenin gene.

Ectopic expression of certain Wnt genes in mouse mammary tissue is tumorigenic, and mutations that stabilize beta-catenin are found in various human cancers including colorectal cancer. To determine the role of stabilized beta-catenin in intestinal tumorigenesis in mice, we constructed by embryonic stem (ES) cell-mediated homologous recombination, a mutant beta-catenin allele whose exon 3 was sandwiched by loxP sequences. When the germline heterozygotes were crossed with mice expressing Cre recombinase in the intestines, the serines and threonine encoded by exon 3 and to be phosphorylated by glycogen synthase kinase 3beta (GSK3beta) were deleted in the offspring intestines, which caused adenomatous intestinal polyps resembling those in Apc(Delta716) knockout mice. Some nascent microadenomas were also found in the colon. These results present experimental genetic evidence that activation of the Wnt signaling pathway can cause intestinal and colonic tumors.

Animals↗