Biomedical subjects

M Kitada

Publications and source records attributed to M Kitada.

At least 73 records · Page 4Linked to original sources

PubMed1997

Bioactivation of monocrotaline by P-450 3A in rat liver.

Monocrotaline (MCT) is bioactivated in liver cytochrome P-450s to MCT pyrrole (MCTP), which primarily injures the lung endothelium to result in the development of pulmonary hypertension (PH) in rats. However, whether there is a relation between the degree of PH and the activity of liver cytochrome P-450 to convert MCT to MCTP remains unclear. To examine the relation between these physiological and biochemical changes, we first measured the severity of MCT-induced (20 mg/kg) PH in male, female, castrated male, and phenobarbital (PB, liver P-450s inducer)-pretreated male rats. The degree of right ventricular hypertrophy was more severe in PB-pretreated male than in control male rats. It was also more severe in male than in either female or castrated male rats, suggesting that sex-specific P-450s could be involved in the metabolic pathways of MCT in the liver. Further to explore which of the isozymes (2A2, 2C11, and 3A) of P-450s in the liver is responsible for the bioactivation of MCT, we measured the rate of MCTP production in hepatic microsomes by a modified Mattock's method. Treatment of male rats with PB and pregnenolone 16alpha-carbonitrile (PCN), which is the specific inducer of P-450 3A, increased the rate of MCTP production, suggesting that P-450 3A may contribute to the conversion to pyrrole. Therefore we measured the amount of P-450 3A protein by immunoblotting and attempted to inhibit MCT metabolism by using antibodies to P-450 3A. P-450 3A was significantly induced by PCN (6.5-fold) and PB (4.6-fold) treatment and reduced by castration (0.38-fold). The amount of P-450 3A was closely correlated with the production of MCTP, and the conversion of MCT to MCTP was strongly inhibited by antibodies against P-450 3A. These results indicated that P-450 3A was predominantly responsible for the metabolism of MCT to MCTP in rat liver and suggested a tight linkage between the degree of PH and the activity of liver P-450 3A.

Animals↗

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

[Multidrug-resistance by induction of inactivation for anti-cancer drugs].

There are several major groups of multidrug resistance mechanisms. 1) The multidrug resistant phenotype. 2) Glutathione S-transferences (GST) and detoxification mechanisms. 3) Topoisomerase I and II. 4) DNA repair. 5) Drug activation by cytochrome P450 (P450). In this article the biochemical functions of GST and P450 are described to show how individual enzymes contribute to resistance to carcinogens and anti-tumor drugs. Cancer cell lines indicated resistant to anti-cancer drugs, such as mitomycin C, doxorubicin, tamoxifen, cyclophosphamide and their derivatives, by a high activity of GST and a low activity of P450 in general. However, the mechanism of change of these enzyme activities is complicated and different in each drug. We show the study on the mechanism of multidrug resistance using cancer cell lines.

Animals↗

PubMed1997

[A study on low grade malignant tumors arisen in the trachea and the bronchus].

Twelve patients who suffered from low grade malignant tumors arisen in the trachea and the bronchus (6 of carcinoid, 4 of mucoepidermoid carcinoma, and 2 of adenoid cystic carcinoma) underwent surgical treatment from 1977 to 1996 in our department. Operations included 1 sleeve resection of the trachea, 1 patch plasty of the trachea, 3 sleeve lobectomies, and 7 lobectomies. Lymph node dissection was performed in 9 of 12 cases. Metastases in lymph nodes were not found in all 12 cases. Five year survival rate of low grade malignant tumors arisen in the trachea and the bronchus was 78.8% and better than that of stage I lung cancers.

Adolescent↗

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

Nucleotide sequence of pi class glutathione S-transferase in human fetal liver.

The GST Fpi and GST Ppi, pi class glutathione S-transferase (GST), were purified from human fetal livers and placentas, respectively. Both GST enzymes were indistinguishable each other in their subunit molecular weights, immunochemical properties and substrate specificities. Three clones (pFGP-1, pFGP-2 and pFGP-3) coding for the pi class GST purified from fetal livers were isolated from a human fetal liver cDNA library. The full-length clone encodes a polypeptide comprising 210 amino acid including the initiator methionine. All of these cDNA clones were nearly identical to a human placental cDNA clone, pGpi 2. The pFGP-1 cDNA had only a single base transition accompanied by an amino acid transition in the coding region, at position 313. The pFGP-2 and pFGP-3 cDNAs were also nearly identical to pGpi 2 cDNA, having only a single silent C-->T transition in the coding region, at position 555.

Amino Acid Sequence↗

PubMed1996

Stereoselectivity in bunitrolol 4-hydroxylation in liver microsomes from marmosets and Japanese monkeys.

The stereoselectivity in 4-hydroxylation of bunitrolol (BTL), a beta-adrenoreceptor blocking agent, was examined in liver microsomes from monkeys (marmosets and Japanese monkeys) and compared with the results of human liver microsomes. The formation of (+)-4-OH-BTL from (+)-BTL from (+)-BTL was significantly higher than that of (-)-4-OH-BTL from (-)-BTL in the liver microsomal fractions from the two kinds of monkeys. The 4-OH-BTL-forming activity from racemic BTL was significantly lower than from enantiomeric BTL, indicating a possible metabolic interaction between BTL enantiomers. The in vitro profiles observed in the monkeys were very similar to those in humans, but the stereoselectivity in BTL metabolism [(+)-BTL > (-)-BTL] in the primates was found to be reverse to that in rats [S. Narimatsu et al., Anal. Biochem., 222, 256-261 (1994)]. The 4-OH-BTL-forming activity from BTL enantiomers was significantly suppressed by quinidine and quinine, while the former was more potent than the latter, and also by alpha-naphthoflavone. Furthermore, the activity was also suppressed by antisera against rat cytochromes P450-2D2 and -1A2 in concentration-dependent manners. However, kinetics showed that enantiomeric BTL 4-hydroxylation was monophasic in liver microsomes from marmosets of both genders and from male Japanese monkeys. These results suggest that cytochrome P450-2D and -1A enzymes with similar Km values are involved in BTL 4-hydroxylation in monkey liver microsomes.

Adrenergic beta-Antagonists↗

PubMed1996

Formation of 2-sulphamoylacetylphenol from zonisamide under aerobic conditions in rat liver microsomes.

1. The antiepileptic agent zonisamide, 1,2-benzisoxazole-3-methanesulphonamide, was metabolized reductively to 2-sulphamoyl-acetylphenol (SMAP) not only under anaerobic conditions but also under aerobic conditions in liver microsomes of rat pretreated with phenobarbital or dexamethasone. 2. NADPH was required for the formation of SMAP from zonisamide under aerobic conditions. In addition, the reductive metabolism of zonisamide under these conditions was substantially inhibited by carbon monoxide, ketoconazole, and cimetidine, known inhibitors of cytochrome P450. 3. The formation of SMAP under aerobic conditions in liver microsomes was increased by pretreatment of rat with triacetyloleandomycin (TAO) and was increased by the treatment of the microsomes with ferricynaide. 4. These results imply that zonisamide is metabolized reductively to SMAP by a cytochrome P450 belonging to the 3A subfamily under aerobic conditions as well as anaerobic conditions.

Aerobiosis↗

PubMed1996

[Clinical evaluation of granisetron hydrochloride against nausea and vomiting induced by anticancer drugs for gynecological malignant tumors].

We, in the Department of Obstetrics and Gynecology, Kansai Medical College, conducted an evaluation of the usefulness and safety of granisetron hydrochloride used for nausea and vomiting due to chemotherapy in patients with gynecological malignant tumors, with an additional study of the efficacy of different regimens. The subjects were 9 patients in whom 16 courses of CAP therapy were given (group A) and 13 patients in whom 24 courses of CAP therapy were given (group B). Granisetron hydrochloride 3 mg/body was administered by intravenous drip in the two groups before chemotherapy. Clinical symptoms of nausea, vomiting, and anorexia were observed for 2 days after anticancer drugs were administered in order to evaluate its efficacy. The percentage of patients who responded as "effective" or better was 90.0%. In different regimens, the efficacy was 93.8% in group A and 87.5% in group B. These results indicated clinically high usefulness in both groups. No side effects related to granisetron hydrochloride were found in this study.

Adult↗

PubMed1996

[Expression of major histocompatibility complex of advanced non-small cell lung cancer (NSCLC)].

Expression of major histocompatibility complex of lung cancer was examined to study the malignant potential of the tumor using immunochemical staining (anti-HLA class I monoclonal antibody; w6/32). Nuclear DNA contents and the labeling index of proliferating cell nuclear antigen (PCNA) were measured as well. Forty three advanced (p-stage IIIa) lung cancers resected by lobectomy (33 cases), pneumonectomy (9 cases), and segmentectomy (1 case) entered the study. Mediastinal lymph node dissection was performed in every case during the operation. Of the 43 cases, expression of HLA class I was positive in 17 and negative in 26. The patients with positive HLA expression showed significantly better prognosis than those with negative HLA expression in terms of 5 year survival (p < 0.01). The patients with aneuploid pattern and positive HLA class I expression had the best prognosis on the survival curve (p < 0.01). When the PCNA positive rate was high, the prognosis was poor. And the patients with negative PCNA and positive HLA class I expression had significantly better prognosis than the others (p < 0.01). These findings suggest that the expression of HLA class I on the tumor cells is an important prognostic factor in the patients with NSCLC.

Carcinoma, Non-Small-Cell Lung↗

PubMed1996

[Pulmonary aspergillosis: clinical findings and surgical treatment].

Between 1980 and 1995, 10 patients underwent thoracotomy for pulmonary aspergillosis. In six patients, hemoptysis and bloody sputum were the chief complaints. The other complaints were nonspecific. Six patients had a history of pulmonary tuberculosis, and two of those patients underwent upper lobectomy. Aspergillosis had developed in the residual space. A fungus ball was observed on the preoperative chest X-ray and CT scan films in seven patients. Lobectomy was done in three patients, segmentectomy in two, and partial pulmonary resection in four. The patients with lesions that had grown in the residual space underwent curettage with muscle plombage. Three patients underwent thoracoplasty. An additional operation was done in two patients because of poor residual lung expansion. No patient had recurrence. We conclude that surgical treatment should be based on symptoms and on pathological findings.

Adult↗

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

[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

[Surgical treatment of primary mediastinal tumors in children].

Twenty children with primary mediastinal tumor underwent surgical treatment. Ten patients had benign tumor and the other patients were malignant. Seven of ten patients with malignant tumor were neurogenic, and 3 patients were of germ cell tumor. In the clinical manifestation, 11 patients were asymptomatic. All of benign tumors were resected completely, but in a few patients with malignant tumors, the complete resection not possible. However, except for one patient with immature teratoma, all patients with malignant tumor have been surviving following postoperative chemotherapy and radiotherapy. Two infants with bronchogenic cyst were operated on their respiratory distress syndrome in emergency, and have been salvaged.

Adolescent↗

PubMed1996

[Study of revasularization of tracheal graft in a canine autotransplantation model--a novel technique to promote blood supply to a long graft].

The success of tracheal transplantation largely depends on the revascularization process of the graft. We studied blood supply to the graft with 7 tracheal rings in an autotransplantation model; Group I, II and III. Then, a technique to promote blood supply to the graft with 14 tracheal rings was evaluated; Group IV and V. In group I, autotransplantation of the graft with 7 tracheal rings to the intact host trachea was performed. In group II, peritracheal sheath was dissected from the host trachea in the length of 2 tracheal rings prior to autotransplantation of the same graft. In group III, omentopexy was added to the graft of group II. In group IV, two circular incisions into the tissue between the 4-5th cartilage from the host trachea except the posterior wall were made in the graft with 14 tracheal rings. Omentopexy was added to the graft was autotransplanted to the intact host trachea. In group V, a procedure similar to that of group IV was performed without circular incisions in the graft. The rate of successful transplantation in group I, II, III, IV and V was 82.1%, 0%, 72.7%, 76.8% and 16.7% respectively. In the successful groups with transplantation (I, III, IV), establishment of blood supply through the newly developed blood vessels on the mucosal and outer surface of the anastomotic site was observed between 4 and 7 postoperative day. At that time, recanalization of the native vessels in the graft via new vessels was observed. The omentopexy enhanced the blood supply at the anastomotic sites, but it showed no improvement of the blood supply in the middle portion of the graft with intact sheath. The circular incisions in the long graft had additional effect on enhancement of blood supply to the middle portion of the graft. In conclusion, preservation of the host peritracheal sheath, omentopexy, in general, and the circular incisions in the long graft were the keys for successful tracheal transplantation.

Animals↗

PubMed1995

Fluorescent substances and high molecular weight protein aggregates formed in rat heart mitochondria upon doxorubicin-induced lipid peroxidation.

A rat heart mitochondrial suspension was incubated with doxorubicin, FeCl3 and NADH. Fluorescent substances and high molecular weight protein aggregates were observed in the mitochondrial membranes upon the formation of thiobarbituric acid-reactive substances. Since both fluorescent substances and high molecular weight protein aggregates are retained in mitochondrial membranes, they can be of use in the clarification of the site of doxorubicin-induced lipid peroxidation.

Animals↗