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Biomedical subjects

K Kanazawa

Publications and source records attributed to K Kanazawa.

At least 109 records · Page 6Linked to original sources
PubMed1998

Tryptophan pyrolysis products, Trp-P-1 and Trp-P-2 induce apoptosis in primary cultured rat hepatocytes.

The cytotoxicity of heterocyclic amines, dietary carcinogens derived from cooked foods, to primary cultured rat hepatocytes was studied. A tryptophan pyrolysis product, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) was the most cytotoxic of 11 compounds tested. Trp-P-1 was found to induce apoptosis as measured by morphological changes in nuclear chromatin and internucleosomal DNA fragmentation. 3-Amino-1-methyl-5H-pyrido[4,3-b] indole (Trp-P-2) showed a moderate apoptotic effect, and other compounds had a similar but weaker effect.

Animals↗
PubMed1998

Antimutagenicity of flavones and flavonols to heterocyclic amines by specific and strong inhibition of the cytochrome P450 1A family.

We found the mechanism in flavonoids that can strongly suppress the mutagenicity of one of the food-derived and carcinogenic heterocyclic amines, 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2). The antimutagenicity was evaluated by IC50 value, the amount required for 50% inhibition of the mutagenicity of 0.1 nmol Trp-P-2, with Salmonella typhimurium TA98 strain in the presence of S9 mix. The flavones and flavonols were two orders stronger as antimutagens that such antimutagenic phytochemicals as chlorophylls and catechins. We had previously found flavonoids to be a desmutagen to neutralize Trp-P-2 before or during attack of DNA, because they had no effect on either the ultimate mutagenic form of Trp-P-2 (N-hydroxy-Trp-P-2) or the mutated cells. The desmutagenicity of the flavonoids did not depend on the hydroxy number or position that should be associated with antioxidative potency, and was also unaffected by the solubility of Trp-P-2 in the assay solution. The inhibitory effect of the flavonoids on the metabolic activation of Trp-P-2 to N-hydroxy-Trp-P-2 was almost in parallel with the antimutagenic IC50 value, when determined with a Saccharomyces cerevisiae AH22 cell simultaneously expressing both rat cytochrome P450 1A1 and yeast reductase. The Ki values of flavones and flavonols for the enzyme were less than 1 microM, while the K(m) value of Trp-P-2 was 25 microM. The antimutagenicity of the flavones and flavonols was thus concluded to be due to inhibition of the activation process of Trp-P-2 by P450 1A1 to the ultimate carcinogenic form. They were also able to act as antimutagens toward other indirect mutagens that were activated by P450 1A1.

Animals↗
PubMed1998

5-HT1Dbeta receptor mediates the supersensitivity of isolated coronary artery to serotonin in variant angina.

Although serotonin (5-hydroxytryptamine; 5-HT) is used for provocation of coronary spasm, 5-HT receptor subtypes in spastic coronary arteries remain undetermined. We demonstrated the supersensitivity of isolated coronary artery to ergonovine, 5-HT, and sumatriptan, a 5-HT1D receptor agonist, in a patient with variant angina. Furthermore, we detected gene expression of 5-HT1Dbeta and 5-HT2A receptors in spastic coronary artery using RNase protection assay. These findings suggest that the leftward shift of the dose-response curve for 5-HT, which plays an important role in the pathogenesis of coronary spasm, is mediated by activation of 5-HT1Dbeta receptor.

Angina Pectoris, Variant↗
PubMed1998

Xenobiotic tolerance of primary cultured hepatocytes in rats fed a high-fat or high-protein diet.

The diet and nutritional status dominate a tolerance to environmental xenobiotics. In this study, the cytotoxic action of carbon tetrachloride (CCl4) and 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), one of the dietary carcinogens, was investigated using primary cultured hepatocytes from rats fed a high-fat (23% corn oil) or high-protein (50% casein) diet for three weeks. Both chemicals showed strong cytotoxicity to hepatocytes, which was judged by measurement with the MTT-test and lactate dehydrogenase leakage test. A dietary effect on cytotoxicity was observed; hepatocytes from rats fed the high-protein diet were more susceptible to cytotoxicity than the cells from rats fed a standard diet. On the other hand, ureogenesis, as a cellular function of hepatocytes, was markedly decreased in the cells from rats fed the high-fat diet. These activities were affected in the CCl4-treated cells but not in the Trp-P-1-treated cells. The same trend of both diet and chemical effects was observed in gluconeogenesis from fructose. We conclude that the hepatocytes from rats fed a high-protein diet have high susceptibility to the cytotoxicity of CCl4 and Trp-P-1, but cytotoxicity was not related to the reduction of cellular functions.

Animals↗
PubMed1998

[Three cases of colorectal cancer with lung metastasis successfully treated with combination chemotherapy using 5'-DFUR and MMC].

Three patients with colorectal cancer and pulmonary metastasis who had previously undergone surgical treatment, were treated by combination chemotherapy with CDDP and 5-FU regimen, but the growth of the metastatic tumor could not be controlled finally. Thus, a new strategy of combination chemotherapy using 5'-DFUR and MMC were investigated in these cases, and resulted in suppressing the tumor growth successfully without admission. The procedure for treating pulmonary metastasis of colorectal cancer has not been established clearly. This new regimen may play an important role from the standpoint of not only its effectiveness against tumor growth but also the quality of life of patients.

Adult↗
PubMed1998

Trophoblastic disease: twenty years' experience at Niigata University.

The author engaged in the registration work and the clinical studies of trophoblastic disease over 20 years at Niigata University in Niigata prefecture, before transferring to University of the Ryukyus in Okinawa prefecture in 1992. In this paper, the following four topics are reviewed and discussed. 1) the registration data of trophoblastic disease in Niigata prefecture, 2) the treatment results of gestational chorio-carcinoma at the Niigata University Hospital, 3) a trial administration of Gn-RH analogue in patients with gestational choriocarcinoma to suppress secretion of hCG-like substance (hLS) which might cross-react anti-hCG antibodies in hCG immunoassay system, 4) the two rare cases of extrauterine gestational choriocarcinoma who were presented to the Ryukyus University Hospital.

Adult↗
PubMed1997

Disparity between serotonin- and acetylcholine-provoked coronary artery spasm.

BACKGROUND AND HYPOTHESIS: Intrinsic vasoactive substances, such as serotonin and acetylcholine, are known to provoke coronary artery spasm in patients with vasospastic angina. It remains unclear, however, whether these different agents, which activate different receptors, produce spasms at the same sites in these patients. The present study was designed to clarify the disparity of receptor agonist-induced coronary artery spasms in the same patients. METHODS: We conducted sequential provocative tests of coronary artery spasm by acetylcholine, serotonin, and ergonovine in 20 patients with rest angina examined with quantitative coronary angiography. RESULTS: Coronary artery spasms were provoked in all patients at 27 spastic sites. In 13 patients, ergonovine provoked spasms and in 10 of 13 patients who were diagnosed with variant angina, both acetylcholine and serotonin provoked spasms at the same sites where ergonovine also did. In 4 of 13 patients, spasms were provoked by serotonin but not by acetylcholine. In the remaining seven patients, whose spasms were induced by ergonovine, spasms were produced by acetylcholine but not by serotonin. On coronary angiography, the spastic sites for both acetylcholine and serotonin, and those for serotonin alone, were located in the proximal segments of coronary arteries, whereas the spastic sites for acetylcholine alone were located in the distal segments. CONCLUSIONS: This study documented the disparity between serotonin- and acetylcholine-induced spasms. Provocative tests using agents that activate different receptors may produce coronary artery spasms at the same and/or different sites, and this disparity may reflect the clinical heterogeneity of vasospastic ischemic syndrome.

Acetylcholine↗
PubMed1997

Therapeutic value of neoadjuvant intra-arterial chemotherapy (cisplatin) and irradiation for locally advanced uterine cervical cancer.

We analyzed long-term treatment results in 51 patients with locally advanced uterine cervical carcinoma (IIB, 4; IIIB, 43; IVA, 4) treated with neoadjuvant intra-arterial (I-A) chemotherapy (cisplatin) via the uterine artery and irradiation. Thirty patients (58.8%) developed recurrence. Twelve had pelvic recurrence alone, 8 had distant metastases alone, and 10 had both pelvic and distant failure. The 5-year cumulative pelvic control rate, absolute survival rate, and disease-free survival rate were 55.3, 47.1, and 39.4%, respectively. Eight of 51 patients (15.7%) suffered late complications. These results suggest that our neoadjuvant I-A chemotherapy prior to irradiation has limited additional value for long-term prognosis in patients with locally advanced uterine cervical carcinoma.

Adult↗
PubMed1997

Synergistic effects of hyperthermia in preoperative radiochemotherapy for rectal carcinoma.

PURPOSE: We investigated the effectiveness of hyperthermia added to preoperative radiation and chemotherapy for the treatment of rectal carcinoma. METHODS: Forty-one patients receiving preoperative radiation were divided into two groups, Group A (20 patients; receiving radiation, hyperthermia, and chemotherapy) and Group B (21 patients, receiving no hyperthermia). Total dose of radiation was 40.5 Gy. Hyperthermia was administered using 8 MHz of radiofrequency. Rectal temperature reached 42 degrees C. A total dose of 3,400 mg of 5-fluorouracil given by suppository was used as the chemotherapeutic agent. Effect of the preoperative treatment was assessed by tumor reduction on barium enema, histologic findings of the resected specimens, area measurement of the residual cancer tissue, and by silver-staining nucleolar organizer region (AgNOR) score. RESULTS: Tumor reduction on barium enema was significantly greater in Group A than in Group B (P < 0.01). Excluding two cases of mucinous carcinoma because a large acellular mucinous accumulation added materially to the cancerous area, the ratio of residual cancer area to total lesion size in Group A was significantly smaller than in Group B (P < 0.05). AgNOR score of the resected tumor tended to be smaller in Group A than in Group B. CONCLUSION: Addition of hyperthermia resulted in a greater degree of tumor necrosis and was considered to be useful as a preoperative treatment for rectal carcinoma.

Adenocarcinoma↗
PubMed1997

Ki-ras point mutation in different types of colorectal carcinomas in early stages.

PURPOSE: The aim of this study was to elucidate pathways of carcinogenesis in the colon and rectum by investigating Ki-ras point mutation in different types of colorectal carcinomas in the early stage. METHODS: We analyzed rates of Ki-ras codon 12 mutations in 34 small, polypoid-type carcinomas (Tis or T1), 21 superficial-type carcinomas (Tis or T1), and 42 advanced carcinomas (T2, T3, and T4). RESULTS: Frequency of Ki-ras mutations in superficial-type carcinomas was 14.3 percent (3/21), which was significantly lower than 50 percent (17/34) in small polypoid carcinomas and 40.5 percent (17/42) in advanced carcinomas. These data suggest that another pathway of colorectal carcinogenesis that does not involve Ki-ras point mutation might exist. Among the 17 small polypoid carcinomas with Ki-ras point mutation in which both adenomatous and carcinomatous tissue were examined, 12 showed a mutation of the same type in both carcinomatous and adenomatous tissues. In two cases, mutation was present only in carcinomatous tissue and not in adenomatous tissue; in the other three cases, Ki-ras point mutation was present only in adenomatous tissue but not in carcinomatous tissue. CONCLUSIONS: These data suggest that carcinoma in a small polypoid lesion does not always develop from pre-existing adenoma with Ki-ras point mutation; in a small number of the polypoid-type early carcinomas, polyclonal composition concerning the Ki-ras gene may exist.

Adenocarcinoma↗
PubMed1997

Anal sphincter reconstruction with a pudendal nerve anastomosis following abdominoperineal resection: report of a case.

PURPOSE AND METHODS: We report herein a case of a patient with rectal carcinoma in whom a new anus was constructed following an abdominoperineal resection of the anorectum. This is the first reported case in which reconstruction of the anal sphincter was performed using the lower part of the gluteus maximus muscle with a pudendal nerve anastomosis. The pudendal nerve anastomosis maneuver was designed to achieve proper innervation and function of the external anal sphincter. This newly reconstructed sphincter was physiologically evaluated after surgery. RESULTS: The patient's defunctioning colostomy was not closed following his initial surgery because part of the transposed muscle was devitalized by infection following blood flow damage. However, purposeful contraction of the new sphincter was easy to achieve without special training. The patient's rectal sensation for the desire to defecate was satisfactory. Electromyographic studies demonstrated that the newly reconstructed anal sphincter had characteristics of the original external anal sphincter. CONCLUSIONS: This method is a promising procedure for reconstructing the anal sphincter.

Aged↗
PubMed1997

Alpha-fetoprotein-producing carcinoma of the colon: report of a case.

We report herein the rare case of a 67-year-old man in whom alpha-feto-protein (AFP)-producing carcinoma originated in the transverse colon, describing the clinical course of the patient and the histological features of the tumor. At the age of 63, the patient had been diagnosed as having sigmoid colon carcinoma, and surgery was carried out. However, 4 years later, his fecal occult blood test was positive, and further investigation revealed a transverse colon carcinoma with liver metastasis. The serum AFP measured preoperatively was 10978 ng/ml. Resection of the transverse colon and a liver biopsy were performed, following which his serum AFP level decreased to 4804 ng/ml. Histology of the ulcerated lesion in the transverse colon showed a poorly differentiated adenocarcinoma with a medullary growth pattern. Using an immunohistochemical staining method, AFP-producing cells were detected in the transverse colon carcinoma and the liver metastasis. Based on our experience of this patient and a review of the literature on the few cases previously reported, we conclude that AFP-producing coloretal carcinoma has a tendency to produce blood-borne metastasis and to be associated with a poor prognosis.

Aged↗
PubMed1997

The beneficial effects of recombinant human insulin-like growth factor-I (IGF-I) on wound healing in severely wounded senescent mice.

The effects of recombinant insulin-like growth factor I (rIGF-I) on wound healing were tested using senescent and young BDF-1 mice, aged 108 weeks and 10 weeks, respectively. After inflicting a full thickness dermal burn encompassing 15% of the body surface, a skin incision, 2 cm in length, was made in the back. A silicone tube containing a piece of polyvinyl sponge was then implanted into a subcutaneous pocket in the flank to collect body fluid. An osmotic pump was buried in the abdominal subcutaneous tissue for the continuous infusion of rIGF-I, the control being treated with the solvent of IGF-I, physiological saline, only. The administration of IGF-I produced favorable effects on wound healing in the senescent mice, shown by enhanced tensile strength and an elevated concentration in the hydroxyproline of the polyvinyl sponge content. The IGF-I-treated severely wounded senescent mice healed better than their counterparts and their skeletal muscles contained more glutamine. Furthermore, they showed more enhanced cutaneous hypersensitivity towards dinitrofluorobenzene than the controls, suggesting an enhanced grade of cellular immunity. There were no conspicuous differences between the two groups of young mice. These data may suggest the beneficial effects of rIGF-I on wound healing, especially in geriatric surgery.

Age Factors↗
PubMed1997

Functional perineal colostomy with pudendal nerve anastomosis following anorectal resection: a cadaver operation study on a new procedure.

BACKGROUND: We have previously studied functional perineal colostomy that used skeletal muscle with pudendal nerve anastomosis (PNA) following anorectal resection in an animal model. In that study the neosphincter reconstructed with PNA achieved the proper functions of the external anal sphincter resulting in a satisfactory defecatory condition. This study was a preliminary step before applying this procedure to human beings. METHODS: We reconstructed a new anal sphincter by using the lower part of the gluteus maximus muscle (lower GMM) with PNA in a total of six sides of four human cadavers and investigated the anatomic problems associated with this procedure. RESULTS: We classified the branching patterns of the inferior gluteal nerve into three types. The length of the branches of the inferior gluteal nerve to the lower GMM varied from 32 to 76 mm (median, 57 mm). The length of the pudendal nerve (PN) passing out below the sacrotuberous ligament varied from 21 to 44 mm (median, 29.5 mm). The PN was anastomosed to the nerve innervating the lower GMM with the redundancy of 17 to 36 mm (median, 24.5 mm). In all cases the anal sphincter reconstruction with a PNA maneuver was anatomically feasible by using the lower GMM. The length of the new anal canal was 65 to 80 mm (median, 67.5 mm). CONCLUSIONS: The PNA maneuver was an anatomically applicable method to make a neoanus in human beings. Preparation for the application of this method to human beings was accomplished.

Aged↗
PubMed1997

Low-dose N omega-nitro-L-arginine methyl ester treatment improves survival rate and decreases myocardial injury in a murine model of viral myocarditis induced by coxsackievirus B3.

Recent reports demonstrated the expression of inducible-type NO synthase in the heart of viral myocarditis. Since NO has multiple biological actions, a substantial amount of NO produced in the diseased heart may act either as a cytotoxic or as a cytoprotective molecule in the process of myocarditis. In the present study, we examined the effect of inhibition of NO synthesis on the mortality and the extent of myocardial injury in a murine model of coxsackievirus B3-induced myocarditis. We fed the infected mice drinking water containing a relatively low concentration (0.37 mmol/L) of N omega-nitro-L-arginine methyl ester (L-NAME) for 14 days after virus inoculation. This dose of L-NAME did not change virus titers in the heart. However, L-NAME-fed mice showed a significant reduction in mortality compared with those fed normal drinking water (nontreated mice). On the contrary, mice given a higher concentration of L-NAME (3.7 mmol/L) exhibited increased mortality. In addition, mice fed a low concentration of L-NAME showed reductions in the severity of heart failure and in the area of myocardial necrosis. Although systemic blood pressure was reduced in nontreated mice, in mice fed a low concentration of L-NAME, it was maintained at a level similar to that in uninfected control mice, L-NAME-treated mice also exhibited a reduction in the degree of inflammatory cell infiltration associated with decreased production of tissue prostaglandin E2 levels in the heart compared with nontreated mice. Therefore, NO is likely to be involved in the pathogenic mechanisms of myocardial injury and resultant cardiac dysfunction in a murine model of coxsackievirus B3-induced viral myocarditis.

Animals↗
PubMed1997

Effects of dietary lipid peroxidation products on hormonal responses in primary cultured hepatocytes of rats.

Dietary lipid peroxidation products cause endogenous lipid peroxidation with hepatic dysfunction. In this study, we isolated and cultured hepatocytes of rats that were given secondary autoxidation products of linoleic acid (p.o., 400 mg/rat/day for 3 days), and examined the hormonal responses of these hepatocytes. An increase in thiobarbituric acid reactive substances and a depletion of vitamin E persisted in hepatocytes from treated rats for at least 24 h in culture as compared to those from control rats. As markers for hepatic dysfunction, the activities of six enzymes were measured. In each case, there was an initial decrease in the enzyme activity in hepatocytes from the treated rats, and all activities were restored by 48 h in culture. Then, we measured the hormonal responses of these hepatocytes. The responses to insulin or glucagon in hepatocytes from secondary products-treated and control rats were the same. In contrast, the response to dexamethasone was significantly lowered in hepatocytes from secondary products-treated rats as measured by the induction of tryptophan 2,3-dioxygenase and tyrosine aminotransferase. We conclude that primary cultured hepatocytes from the rats treated in vivo with dietary lipid peroxidation products retained symptoms of oxidative stress and had a low response to glucocorticoids.

Animals↗
PubMed1997

Ultrasonographic evaluation of lower uterine segment to predict the integrity and quality of cesarean scar during pregnancy: a prospective study.

A prospective randomized study was conducted to measure the serial thickness of the lower uterine segment (LUS) by transvaginal ultrasonography in a control group of 80 women having no history of uterine surgery and in a study group of 43 women having a history of previous cesarean section (C/S). In the study group, more than 2 mm of thickness of the LUS was considered as good healing and less than 2 mm of thickness as poor healing. After serial sonographic examination, the women with good healing were given trial for labor unless an obstetrical indication for C/S existed. The appearance of the LUS during surgery was compared with antenatal ultrasonographic assessment by direct inspection. Twenty two (79%) of 28 women with a well healed scar had trial labor with the result that 46% had a successful vaginal birth without any uterine rupture of dehiscence. Eight women with poor healing all had elective C/S. Seven women with a 2 mm LUS thickness were individually categorized for delivery mode. Two of those women delivered vaginally. The LUS was found to be thin to translucent in these later two groups. Two mm or less as a criterion for poor healing had the sensitivity and specificity of 86.7% and 100% respectively. The positive predictive value was 100% and the negative predictive value was 86.7%. Ultrasonographic evaluation is effective in predicting the quality of a uterine scar and in differentiating the risk group of probable uterine rupture from the non risk group.

Adult↗