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Biomedical subjects

T Ishikawa

Publications and source records attributed to T Ishikawa.

At least 217 records · Page 12Linked to original sources
PubMed2001

Lightning injury as a blast injury of skull, brain, and visceral lesions: clinical and experimental evidences.

The present study attempts to better understand the mechanism of injuries associated with direct lightning strikes. We reviewed the records of 256 individuals struck by lightning between 1965 and 1999, including 56 people who were killed. Basal skull fracture, intracranial haemorrhage, pulmonary haemorrhage, or solid organ rupture was suspected in three men who died. Generally these lesions have been attributed to current flow or falling after being struck. However, examination of surface injuries sustained suggested that the true cause was concussion secondary to blast injury resulting from vaporization of water on the body surface by a surface flashover spark. To investigate this hypothesis, an experimental model of a lightning strike was created in the rat. Saline-soaked blotting paper was used to simulate wet clothing or skin, and an artificial lightning impulse was applied. The resultant lesions were consistent with our hypothesis that the blast was reinforced by the concussive effect of water vaporization. The concordance between the clinical and experimental evidence argues strongly for blast injury as an important source of morbidity and mortality in lightning strikes.

Adult↗
PubMed2001

Effects of tomato juice consumption on plasma and lipoprotein carotenoid concentrations and the susceptibility of low density lipoprotein to oxidative modification.

Effects of tomato juice supplementation on the carotenoid concentration in lipoprotein fractions and the oxidative susceptibility of LDL were investigated in 31 healthy Japanese female students. These subjects were randomized to one of three treatment groups; Control, Low and High. The Control, Low and High groups consumed 480 g of a control drink, 160 g of tomato juice plus 320 g of the control drink, and 480 g of tomato juice, providing 0, 15 and 45 mg of lycopene, respectively, for one menstrual cycle. The ingestion of tomato juice, rich in lycopene but having little beta-carotene, increased both lycopene and beta-carotene. Sixty-nine percent of lycopene in plasma was distributed in the LDL fraction and 24% in the HDL fraction. In the Low group, the lycopene concentration increased 160% each in the VLDL+IDL, LDL and HDL fractions (p<0.01). In the High group, the lycopene concentration increased 270% each in the VLDL+IDL and LDL fractions, and 330% in the HDL fraction (p<0.01). Beta-carotene also increased 120% and 180% in LDL fractions of the Low and the High groups, respectively. Despite these carotenoid increases in LDL, the lag time before oxidation was not prolonged as compared with that of the Control group. The propagation rate decreased significantly after consumption in the High group. Multiple regression analysis showed a positive correlation between lag time changes and changes in the alpha-tocopherol concentration per triglyceride in LDL, and a negative correlation between propagation rate changes and changes in the lycopene concentration per phospholipid in LDL. These data suggest that alpha-tocopherol is a major determinant in protecting LDL from oxidation, while lycopene from tomato juice supplementaion may contribute to protect phospholipid in LDI, from oxidation. Thus, oral intake of lycopene might be beneficial for ameliorating atherosclerosis.

Adult↗
PubMed2001

Proliferating cell nuclear antigen labeling index and p53 expression predict outcome for breast cancer patients with four or more lymph node metastases.

In general, extensive lymph node metastasis indicates poor prognosis in breast cancer. Nevertheless, some patients with this condition survive for a long time without recurrent disease. This study involved 112 breast cancer patients with four or more lymph node metastases and without distant metastasis who underwent surgery. p53 expression was associated with shorter overall and disease-free survival. High PCNA labeling index was associated with shorter overall disease-free survival. p53-negative and low-PCNA patients survived much longer than p53-positive and high-PCNA patients. This study showed that p53-negative or low-PCNA index patients have relatively good prognoses despite extensive lymph node metastasis.

Adult↗
PubMed2001

Prognostic predictive value of 18F-fluorodeoxyglucose positron emission tomography for patients with pancreatic cancer.

18Fluorine-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) is a unique imaging diagnostic tool to evaluate glucose metabolism and hexokinase activity which may reflect the aggressiveness of a tumor. Thirty-seven patients with primary pancreatic cancer were evaluated with 18F-FDG-PET. Thirteen patients underwent resection for the pancreatic cancer and 24 patients had unresectable tumors. The standardized uptake values (SUV) of 18F-FDG in the primary tumors were calculated. No correlations were found between the SUV in the tumors and the metastatic status to the peritoneal/liver, TNM factors/stage, or resectability. The patients were divided into 2 groups with high and low SUV, with the cut-off value being 3.0 (median SUV value of 37 cases). No differences in the probability of survival were observed between the 2 groups in the patients with resectable tumors. However, in the patients with unresectable tumors, those in the high SUV group had a significantly shorter prognosis than those in the low SUV group. Moreover, a multivariate analysis of survival indicated that SUV is an independent prognostic factor for patients with unresectable pancreatic cancer.

Adenocarcinoma↗
PubMed2001

Apoptosis and thymidylate synthase inductions by 5-fluorouracil in gastric cancer cells with or without p53 mutation.

We studied apoptosis and thymidylate synthase (TS) inductions by 5-fluorouracil (5-FU) in gastric cancer cells with wild-type p53 (MKN-45 and MKN-74) and with mutated p53 (MKN-28 and KATO-III). Apoptotic inductions in MKN-45 and MKN-74 were stronger than those in MKN-28 and KATO-III, suggesting that wild-type p53 may contribute to the induction of apoptosis. After continuous exposure to 0.1 microg/ml of 5-FU for 96 h, no TS induction was obtained in KATO-III, while approximately twice the amount of TS was observed compared to non-treatment cells in MKN-45, MKN-74, and MKN-28. The results of immunohistochemical staining for TS and p53 showed no relation between these two protein expressions in endoscopic biopsy specimens of 25 patients with advanced gastric cancer. These results indicated that p53 status may not play a pivotal role in regulating TS expression. We found no significantly different effects of 5-FU between intermittent (repeat of 24-h continuous infusion and 24-h drug-free) and continuous treatments in either MKN-28 or stem cells (CD34+ hematopoietic progenitor cells) when the same area under the time-concentration curve of 5-FU was administered. The TS induction in MKN-28 cells by intermittent treatment was significantly higher than that by continuous treatment; however, most TSs in both types of 5-FU treatment cells were of the inactive form, i.e., TS bound to FdUMP, a 5-FU metabolite. Therefore, neither intermittent nor continuous treatment appears to induce 5-FU resistance related to the level of increment free TS. In conclusion, our observations suggested that p53 mutation may be associated with apoptotic induction by 5-FU; however, p53 status may not strongly affect TS induction by 5-FU. Intermittent treatment can be replaced with continuous treatment without causing 5-FU resistance.

Antimetabolites, Antineoplastic↗
PubMed2001

TGF-beta1 promotes liver metastasis of pancreatic cancer by modulating the capacity of cellular invasion.

We investigated the effect of TGF-beta1 on liver metastasis of pancreatic cancer using surgical specimens of pancreatic cancer and human pancreatic cancer cell lines Capan-2 and SW1990. Immunostaining of TGF-beta1 showed that TGF-beta1 positivity was significantly related to venous invasion and tumor staging, and also relatively associated with liver metastasis. Cellular invasion and protease production of MMP-2 and u-PA, and in vivo liver metastasis were significantly enhanced after treatment of cells with TGF-beta1. These findings suggest that TGF-beta1 might play an important role in enhancing liver metastasis of pancreatic cancer.

Adenocarcinoma↗
PubMed2001

A comparison of low versus standard dose pravastatin therapy for the prevention of cardiovascular events in the elderly: the pravastatin anti-atherosclerosis trial in the elderly (PATE).

Treatment with low drug doses is generally recommended in the elderly. However, the efficacy of low dose 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor treatment in elderly hypercholesterolemic patients has never been examined. Therefore, we compared the effect of low-dose with standard dose pravastatin, an HMG CoA reductase inhibitor, on the incidence of cardiovascular events (CVEs) in elderly patients with hypercholesterolemia in a randomized prospective trial. Subjects aged > or = 60 years (73 +/- 6 years) with serum total cholesterol (TC) levels of 220-280 mg/dL were randomized to the low-dose (groupL, 5 mg/day; n=334) or standard dose (groupS, 10-20mg/day; n= 331). Baseline TC levels were similar in the 2 groups (253 +/-15 mg/dL). Patients were followed for 3-5 years (mean 3.9 years). TC levels decreased from baseline by 11-13% in group L and by 15-17% in groupS. TC levels at 1 year in S and L group were 209 +/- 2 mg/ dL (16 +/- 1% decrease) and 221+/- 2 mg/dL (12 +/- 1% decrease), respectively. Forty two and 29 CVEs occurred in group L and S, respectively. The incidence of CVEs was significantly lower in group S than in group L (P = 0.046, generalized Wilcoxon test; P = 0.096, log-rank test). The risk ratio for group S compared with group L was 0.674 (95% confidence interval: 0.423-1.074). Subgroup analyses suggested that the difference in the incidence of CVEs between the 2 groups was more clear in subjects without diabetes mellitus, with TC levels of < 253 mg/dL, and with TG levels of > or = 133 mg/dL. The incidence of CVEs in group S was significantly lower than that in group L in subjects without both diabetes mellitus and previous cardiovascular disease (P = 0.026, generalized Wilcoxon test; P = 0.032, log rank test). These findings suggest that standard-dose pravastatin (10-20 mg/day) is more effective in reducing the incidence of CVEs in the elderly than low dose pravastatin (5 mg/ day), especially in nondiabetic elderly patients with mild hypercholesterolemia or previous cardiovascular disease.

Aged↗
PubMed2001

Studies on anti-MRSA parenteral cephalosporins. III. Synthesis and antibacterial activity of 7beta-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2(Z)-alkoxyiminoacetamido-3.

In the course of our exploration for a novel cephalosporin derivative having excellent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), we modified the C-3 linked spacers of cephem derivatives bearing a 1-methylimidazo[1,2-b]pyridazinium-6-yl group at the C-3' position and 2-(5-amino-1,2,4-thiadiazol-3-yl)-2(Z)-cyclopentyloxy-iminoacetyl group at the C-7 position. The optimal spacers were the (E)-2-vinyl and (E)-2-thiovinyl groups seen in 19a and 29aa, respectively. Their anti-MRSA activity was 16 to 32 times as potent as that of cefozopran (CZOP). Focusing on the (E)-2-vinyl and (E)-2-thiovinyl spacers, we further modified the alkoxyimino groups in the C-7 acyl moiety and the 1-alkylimidazo[1,2-b]pyridazinium moieties at the C-3' position and investigated the structure-activity relationships (SAR) of the derivatives. Consequently, we selected 7beta-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2(Z)-fluoromethoxyiminoacetamido]-3-[(E)-2-(1-methylimidazo[1,2-b]pyridazinium-6-yl)thiovinyl]-3-cephem-4-carboxylate (29ca) as a new anti-MRSA parenteral cephalosporin candidate for further biological evaluation. The selected 29ca showed anti-MRSA activity comparable to that of vancomycin (VCM) both in vitro and in vivo, high affinity (IC50)=2.7 microg/ml) for penicillin binding protein 2' (PBP2') of MRSA and potent activity against Gram-negative bacteria as well.

Cephalosporins↗
PubMed2001

Studies on anti-MRSA parenteral cephalosporins. IV. A novel water-soluble N-phosphono type prodrug for parental administration.

A systematic approach for improving the water-solubility of anti-MRSA (methicillin-resistant Staphylococcus aureus) cephalosporin derivatives is described. We first tried to improve the water-solubility of 7beta-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2(Z)-fluoromethoxyiminoacetamido]-3-[(E)-2-(1-methylimidazo[1,2-b]pyridazinium-6-yl)thiovinyl]-3-cephem-4-carboxylate (1a) by substitution of the C-3' pharmacophore. Replacement of the C-3' pharmacophore with a 1-methyl-4-pyridinio group improved the water-solubility without decreasing the anti-MRSA activity. Furthermore, we applied the N-modified prodrug strategy to the C-7 acyl group in order to enhance the water-solubility drastically. Among the compounds prepared, the N-phosphono type prodrugs 2a(1-methylimidazo[1,2-b]pyridazinium derivative) and 2b (1-methyl-4-pyridinio derivative) showed water-solubility appropriate for a product intended for intravenous injection and in vivo anti-MRSA activity comparable to that of vancomycin.

Animals↗
PubMed2001

[Bronchiolo-alveolar cell carcinoma arising after active pulmonary tuberculosis' report of two cases].

We report on two patients diagnosed as having active pulmonary tuberculosis who later developed lung cancer. In both cases, the lung cancer was detected during the treatment of pulmonary tuberculosis. Both patients were initially considered to be experiencing exacerbation of pulmonary tuberculosis. Case 1 was seen in a 74-year-old man. His chest roentgenogram revealed microscopic cavitary lesions with infiltration into both lung fields. His sputum tested positive for acid-fast bacilli. Although he was treated with isoniazid (INH), rifampicin (RFP), ethambutol (EB) and pyrazinamide (PZA), his general condition deteriorated, and the infiltrative shadows in the lung fields had expanded on subsequent chest radiography. Transbronchial lung biopsy (TBLB) yielded findings compatible with a diagnosis of bronchiolo-alveolar cell carcinoma. Case 2 occurred in a 52-year-old man. His chest radiograph revealed cavitary lesions with infiltration into both lung fields. His sputum also tested positive for acidfast bacilli. Despite medication with INH, RFP, EB and PZA, the infiltrative shadow in his chest radiograph increased in size. Bronchiolo-alveolar cell carcinoma was confirmed after examination of the sputum cytology. Case 1 was diagnosed as lung cancer 10 months after being admission to the hospital, and Case 2, seven months after hospitalization. Recent discussion concerning the simultaneous occurrence of pulmonary tuberculosis and bronchogenic carcinoma suggests a high frequency of coexistence of the two diseases. However, the coexistence of active tuberculosis with bronchiolo-alveolar cell carcinoma, as in our cases, is rare.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed2001

[A case of successful management of nonresectable pancreas cancer with liver metastasis by intra-arterial infusion chemotherapy with angiotensin-II and administration of tegafur/uracil].

Nontypical chemotherapy regimens exist for advanced pancreatic cancer. We herein report a 62-year-old man whose nonresectable pancreatic cancer was treated effectively with a new method of intra-arterial regional chemotherapy with angiotensin-II (AT-II). The patient was admitted to our hospital with obstructive jaundice and anorexia. He was diagnosed as having inoperable advanced pancreatic cancer with liver metastasis. Enteric-coated tegafur/uracil (400 mg) was administered for 3 weeks. Simultaneously, intraarterial infusion with 5-fluorouracil (500 mg) and infusion of methotrexate (100 mg) with 50 micrograms of AT-II was given every week. A catheter connected to a subcutaneously implanted port system was placed into the common hepatic artery. As a result of this treatment, the maximum diameter of the pancreatic tumor decreased from 3 cm to 2 cm on the CT-scan. Serum carbohydrate antigen 19-9 (CA19-9) decreased from 24,000 U/ml to 186 U/ml. Moreover, the performance status of patient also improved, and he was discharged from our hospital despite his terminal cancer. This regimen could well be effective in cases of advanced pancreatic cancer.

Angiotensin II↗
PubMed2001

[Inflammatory endotracheal polyp associated with lung cancer treated by high-power diode laser].

A 74-year-old man was admitted to our department for surgery of light lung cancer (c-T1N0 M0 stage IA). Preoperative bronchoscopy revealed a smooth-surfaced polypoid lesion about 3 mm in diameter in the left main bronchus. Pathological findings of the biopsied specimen revealed inflammatory granulation tissue. Right upper lobectomy and lymph node dissection was performed and the pathological diagnosis was squamous cell carcinoma of the lung with no lymph node metastasis (p-T1N0M0 stage IA). Bronchoscopy after 2 and 5 month revealed no change of the polypoid lesion and the biopsied specimen revealed no malignancy. The polypoid lesion was identified microscopically as inflammatory polyp. Therefore, the polypoid lesion was treated with a new high power diode laser system (DIOMED 25, OLYMPUS). Bronchoscopy after 10 month showed complete disappearance of the polypoid lesion.

Aged↗
PubMed2001

[Extracellular matrix degradation enzymes: important factors in liver metastasis of colorectal cancer and good targets for anticancer metastatic therapy].

Extracellular matrix (ECM) degradation enzymes, such as matrix metalloproteinases (MMPs) and plasminogen activators, are important factors in cancer invasion and metastasis, because invasion and metastasis of cancer cells require destruction of mesenchymal collagen or the endothelial basement membrane. Moreover, recent studies have shown that ECM degradation enzymes play important roles in cancer cell proliferation, cancer escape from the immune system, and tumor angiogenesis. ECM degradation enzymes, especially some MMPs, are good targets for anticancer metastatic therapy. Numerous anti-MMP agents have been developed and phase III clinical trials in advanced cancers ongoing. Successful control of MMPs induced by cancer cells will prevent liver metastasis of colorectal cancer.

Colorectal Neoplasms↗
PubMed2001

[Long-term study of airborne allergic pollen count, C. Japonica and cupressaceae in Japan].

We have investigated the distribution of airborne pollen at the different eleven points in Japan from 1987 to 1998 using gravity sampler. To clarify the characteristics causative pollen for Japanese cedar pollinosis, we examined annual change of pollen counts, dispersing period and geographical difference of C. japonica and Cupressaceae pollen. C. japonica pollen occupied much more in Central Japan and Cupressaceae in the west of Japan than the other area. In Hamamatsu City, both of pollen counts were most of all and we found a tendency that the more pollen counts the longer dispersing period. As they reported that at the starting day of pollen in this method some patients had already suffered from allergic symptoms, we considered pollen grains were dispersing in spite of being continuously captured. In these twelve years we found that patients with Japanese pollinosis are exposured by causative agents during about 100 days every spring. But we could not observe the trend of increasing pollen counts and earlier starting day because of global warming. Further more we found that the pollen counts of C. japonica in autumn was increasing since 1994. As one of the factors of increasing patients with pollinosis, we thought that total exposure period of causative pollen every year were longer than that of 1980s.

Air Pollutants↗
PubMed2001

Clinical manifestations of influenza a myocarditis during the influenza epidemic of winter 1998-1999.

OBJECTIVES: The clinical features of myocarditis that developed during the influenza epidemic of winter 1998-1999 were investigated to emphasize the need for medical attention to this disease. METHODS: Nine patients were treated under diagnoses of acute myocarditis during the winter of 1998-1999. Five (two males and three females, mean age 52 +/- 18 years) were examined with myocarditis associated with influenza A. The diagnosis of influenza A myocarditis was based on electrocardiographic and echocardiographic abnormalities, increased creatine kinase levels and at least a four-fold increase in influenza A virus titers using paired sera. RESULTS: All patients had preceding flu-like symptoms and fever. Cardiac involvement developed between 4 and 7 days after the onset of influenza symptoms. Dyspnea progressively worsened in three patients, one went into shock and one had persistent fever, cough and mild dyspnea without apparent cardiac symptoms. Three patients had ST elevation associated with Q waves and one had complete left bundle branch block. The creatine kinase levels were abnormally increased and global wall motion of the left ventricle on echocardiography was decreased in all patients. Two patients had diagnoses of fulminant myocarditis. One patient died of pneumonia following cerebral infarction, but the left ventricular dysfunction normalized in the remaining four patients. CONCLUSIONS: Cardiac involvement occurred between 4 and 7 days after the onset of influenza symptoms, and worsening dyspnea was the most common symptom. Electrocardiography, echocardiography and creatine kinase levels should be checked to determine the potential for cardiac involvement when patients present with suspected influenza associated with worsening dyspnea or prolonged weakness. Increasing the awareness of influenza myocarditis may help in the earlier identification and treatment of this disease during influenza epidemics.

Adult↗
PubMed2001

Effect of a matrix metalloproteinase inhibitor on a lymph node metastatic model of gastric cancer cells passaged by orthotopic implantation.

Lymph node metastasis is the most frequent type of tumor recurrence and is known to be one reason for the poor prognosis in patients with digestive cancer. However, the mechanisms of lymph node metastasis are not clearly understood and a metastatic model will be useful for elucidating factors associated with lymph node metastases. In this study, we investigated the effect of R-94138, a matrix metalloproteinase (MMP) inhibitor, on the lymphnodal metastatic ability of gastric cancer cells using an in vivo orthotopic implantation model in nude mice. Injection of a gastric cancer cell line, MKN-45, into the gastric wall resulted in lymph node metastasis 8 weeks after inoculation. The number of lymph node metastases and the amount of body weight loss significantly decreased by intraperitoneal administration of R-94138. Histologically, lymphatic invasion of cancer cells was found in primary gastric tumors of control mice with lymph node metastasis. However, no lymphatic invasion was observed in the gastric wall of R-94138-treated mice without lymph node metastasis. These findings suggested that the MMP inhibitor, R-94138, could be used in adjunctive therapy for lymph node metastasis in gastric carcinoma.

Acetamides↗
PubMed2001

[Interferon therapy to chronic hepatitis type C for the prevention of hepatocarcinogenesis].

Interferon(IFN) therapy for chronic hepatitis(CH) related by hepatitis C virus is useful for the prevention of the appearance of hepatocellular carcinoma(HCC) by both prospective and retrospective study. IFN could be reduced an activity of necro-inflammatory reaction leading toward the reduction of fibrogenesis. Therefore, IFN treated group had a low potential carcinogenesis of the liver indicating the prevention of HCC from CH type C, even if virological complete remmision(CR) could not be obtained after IFN treatment. Biochemical response(BR) group as well as CR group could be inhibited hepatocarcinogenesis compare with non-IFN treated group. Recently, IFN applied for liver cirrhosis as same concept for the prevention of HCC.

Carcinoma, Hepatocellular↗