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Biomedical subjects

M Fujimori

Publications and source records attributed to M Fujimori.

At least 145 records · Page 8Linked to original sources

Lidocaine metabolism by human cytochrome P-450s purified from hepatic microsomes: comparison of those with rat hepatic cytochrome P-450s.

The metabolism of lidocaine by human hepatic microsomes and purified human cytochrome P-450s, P-450NF (P450IIIA4), P-450MP (a P450IIC form) and P-450PA (P450IA2) was examined and their metabolism was compared with that by rat hepatic cytochrome P-450s. Human hepatic microsomes produced monoethylglycinexylidide (MEGX) and 3-hydroxylidocaine (3-OH-LID) from lidocaine. In a reconstituted system with dilauroylphosphatidylcholine, P-450NF efficiently produced MEGX. P-450PA was not efficient in lidocaine N-deethylation (formation of MEGX) but produced 3-OH-LID. P-450NF and P-450MP did not produce 3-OH-LID. Lidocaine N-deethylation activity of P-450NF was enhanced in a modified reconstituted system with a phospholipid mixture and sodium cholate. P-450NF appears to be an ortholog to rat P450 PB-1 (P450IIIA2). Anti-P450 PB-1 antibody cross-reacted with P-450NF and efficiently inhibited lidocaine N-deethylation in human hepatic microsomes. The correlation of lidocaine N-deethylation activity with the concentration of P-450NF determined immunochemically with anti-P450 PB-1 antibody was good (r = 0.81). In addition, correlation between P-450NF content estimated with anti-P450 PB-1 and anti-P-450NF preparations was good (r = 0.96). These results suggest that rat P450 PB-1 and human P-450NF have closely related properties and P-450NF is the major enzyme involved in lidocaine N-deethylation in human hepatic microsomes.

Adult↗

[Epidural morphine and buprenorphine for postoperative pain relief after hepatectomy].

Postoperative pain relief with epidural morphine and buprenorphine was studied in 33 patients following hepatectomy. Morphine 2mg or buprenorphine 0.06mg in 10ml of normal saline was administered through an epidural catheter inserted at the Th10-11 or L3-4 interspace. Morphine injected at the lumbar level, as well as that injected at the thoracic level produced excellent and long-lasting (20.8 +/- 8.6 hours) pain relief. Respiratory rate decreased significantly following epidural morphine at the L3-4, but PaCO2 did not change. Buprenorphine injected at the thoracic level produced good and long-lasting (22.6 +/- 9.9 hours) pain relief, although buprenorphine injected at the lumbar level produced incomplete analgesia. The epidural administration of morphine 2mg at L3-4 or buprenorphine 0.06mg at Th10-11 may be recommended for postoperative analgesia following hepatectomy.

Adult↗

Clinical evaluation of the response to surgical treatment of Graves' disease.

Included in this study are 513 patients with Graves' disease who underwent thyroidectomy between 1970 and 1983. The patients were divided into three groups by dividing the period in which the surgical procedures were done. The weight of the remnant of the thyroid gland and the incidence of surgical complications were collated for the patients in each group studied. Postoperative function of the thyroid gland was evaluated clinically and biochemically and compared with the remnant weight and total weight of the thyroid gland. The remnant weight was greatest in the first period and least in the third period. There were no differences between the frequencies of postoperative complications among the three groups in site of a remarkable decrease of the remnant weight in the third period. Remission of hyperthyroidism, including those with a latent hypothyroid state, was most frequently observed in the group in which the remnant weight was from 4 to less than 8 grams. These results indicate that the remnant weight appears to be one of the most crucial factors influencing the postoperative outcome; it thus seems appropriate to leave only small remnants of the thyroid gland (4 to less than 8 grams) at thyroidectomy. In our hands, surgical treatment is an effective and safe procedure for Graves' disease, although the precise mechanism for the remission induced by this procedure has not been elucidated.

Graves Disease↗

Metabolism of lidocaine by purified rat liver microsomal cytochrome P-450 isozymes.

The metabolism of lidocaine was studied using rat liver microsomes or a reconstituted lidocaine monooxygenase system with one of eight forms of cytochrome P-450 purified from liver microsomes from untreated- (P450 UT-2 and UT-5), phenobarbital- (P450 PB-1, PB-2, PB-4, and PB-5) or 3-methylcholanthrene- (P450 MC-1 and MC-5) treated rats. A reverse phase high-performance liquid chromatography system capable of simultaneously assaying four major lidocaine metabolites, namely, monoethylglycinexylidide (MEGX), 3-hydroxylidocaine (3-OH LID), methylhydroxylidocaine (Me-OH LID) and glycinexylidide (GX), was employed to determine the rate of formation of each metabolite. Untreated microsomes generated MEGX, Me-OH LID, and 3-OH LID, but the formation of GX was not detected. In male rat liver microsomes, MEGX was the major metabolite of lidocaine when a concentration of 1 mM was employed. The formation of MEGX and Me-OH LID was increased significantly (P less than 0.01) by microsomes from phenobarbital-treated rats, and the formation of 3-OH LID was increased with 3-methylcholanthrene. The study with the reconstituted system with purified cytochrome P-450 isozymes revealed that all eight forms of cytochrome P-450 used have an ability to N-deethylate lidocaine to form MEGX. Among these isozymes, cytochrome P450 PB-4 and P450 UT-2 showed a higher turnover number for the formation of MEGX. Me-OH LID was formed exclusively by P450 PB-5, and 3-OH LID exclusively by P450 MC-1. Selectivity of cytochrome P450 PB-5 for aromatic methyl hydroxylation of lidocaine was confirmed by an inhibition study; formation of Me-OH LID by microsomes of rats treated with phenobarbital was inhibited completely by antibody against P450 PB-5. It was concluded that different cytochrome P-450 isozymes metabolize lidocaine with a different rate and different position selectivities. Since a specific substrate of cytochrome P450 PB-5 (P-450e) is not known, lidocaine may be a useful substrate for the identification of P450 PB-5.

Animals↗

TSH-binding inhibitor immunoglobulin (TBII) in thyroidal venous blood and histological grade of intrathyroidal lymphocyte appearance in Graves' disease.

The aim of this study is to investigate the possibility of determining the appropriate amount of thyroid tissue to leave behind as remnant weight in subtotal thyroidectomy for Graves' disease by measuring the TBII value, and correlating the outcome to the grade of intrathyroidal lymphocyte infiltration. We therefore have investigated the levels of TBII in the thyroidal (T-TBII) and peripheral (P-TBII) venous blood, and the grade of lymphocytic infiltration and lymph follicle formation in the intrathyroidal tissue. There was no parallel relationship between the T-TBII value and the grade of lymphocytic infiltration and lymph follicle formation. There was no marked difference between the T-TBII value and the P-TBII value. It was thus not possible to use these data to determine the proper remnant weight of Graves' thyroid tissue at the time of surgery.

Adolescent↗

[Intra-arterial infusion chemotherapy of locally advanced and recurrent breast cancer].

A total of 15 cases of advanced and recurrent breast cancer of more than 3-year duration were subjected to continuous intra-arterial infusion in our department, and its therapeutic effect and the judgement were examined. Using subclavian artery and internal thoracic artery for the primary cases and the latter artery for the recurrent cases for infusion, continuous administration of 5-FU and one-shot injection of ADM and MMC were performed twice a week. 99mTc-angiography was effective for the identification of arterio-controlled areas. Under the judgement criteria for therapeutic effects according to the breast cancer handling agreement, CR, PR, NC and PD were noted in 1, 8, 5 and 1 cases, respectively, with a 60% rate of effectiveness. Judgement of effects by 201Tl-chloride scintigraphy showed some correlation with the histological judgement, with its apparent effectiveness. Examination of the remote results revealed 3-year survival rate of 83.3% and 3-year healthy survival rate of 66.7% for the primary cases. Two of the 3 recurrent cases died at 2 and 11 post-infusional months, respectively, but 1 showing CR is still alive 4 years and 10 months, post infusionally.

Adult↗

[Local immunotherapy of breast cancer: a case of advanced breast cancer improved by combined local injection therapy with OK-432 and rIL-2].

An effective immunotherapy for breast cancer has yet to be established. We have recently experienced an inoperable case of advanced breast cancer due to mental disorder. Combined local injection therapy with OK-432 and rIL-2 was performed in addition to non-surgical multi-disciplinary treatment, with obvious therapeutic effects. The case is a 67-year-old female, who had a 5.0 x 4.7 cm tumor in the area A of the left mammary gland. Aspiration cytologic examination revealed class V breast cancer. Besides systemic chemotherapy, local injection therapy with OK-432 2.0 KE on day 1 and rIL-2 500 U on day 3 was performed. Upon starting local injection therapy, a rapid reduction was noted in the tumor diameter (reduction rate, 75.5%). Tumor makers of CEA, CA 15-3 also showed obvious diminution. Although the dose and interval of administration remain to be further examined, the combined local injection therapy with OK-432 and rIL-2 was suggested to be an effective local immunotherapy for breast cancer.

Adenocarcinoma, Scirrhous↗

[Therapeutic strategy for adenomatous goiter from the viewpoint of postoperative outcome and epidermal growth factor receptor study].

Adenomatous goiter (AG) is regarded as a benign tumor-like lesion. In the present study, both the postoperative outcome and the localization of epidermal growth factor receptor (EGF-R) were investigated to determine proper therapeutic modalities for AG. In this series, 377 surgical patients were studied. Immunohistochemical observation was carried out according to the ABC procedure. Results were as follows: 1) among the all 377 patients, primary cases were 343 and the remainder, 34 cases (9%), recurrent, 2) majority of the 34 recurrent patients showed multinodular goiter type occupying one whole lobe or both sides. Initial surgical strategy for these cases was only enucleation of the all nodules confirmed macroscopically, 3) coexistence of cancer in AG was observed in 18 cases (5%). Seventeen out of them were latent carcinomas found in the multinodular goiter, and 4) those multinodular patients associated with latent carcinoma revealed presence of EGF-R not only in the malignant lesions but also in the hyperplastic parts. These observations suggest that surgical treatment should be considered for multinodular AG patients. In addition, near-total lobectomy of the diseased side might be recommended as an operative procedure because of the prevention of postoperative recurrence and complications.

Adenoma↗

Cervical catecholamine-secreting paraganglioma in the pterygopalatine fossa.

A 25-year-old man was admitted for examination to determine the cause of hypertension. High levels of noradrenaline in plasma and urine were seen, suggesting that the patient had an adrenal or extra-adrenal pheochromocytoma. However, whole-body scintigraphy using the isotope of [131I] meta-iodo-benzylguanidine (131I-MIBG) failed to find the presence of a catecholamine-secreting tumor. The highest level of noradrenaline was detected in plasma obtained from the left jugular vein after selective venous collections through femoral catheterization. Both the computed tomography and cerebral angiography showed a hen-egg-sized tumor located in the left pterygopalatine. After surgical removal of the tumor, high blood pressure and the levels of noradrenaline in plasma and urine were significantly decreased. Histopathological diagnosis was paraganglioma (catecholamine-secreting paraganglioma). The patient with cervical catecholamine-secreting paraganglioma is the first case where the tumor was isolated and located in the pterygopalatine fossa.

3-Iodobenzylguanidine↗

[Relationship between biopsy and prognosis of breast cancer].

Clinical data from 131 patients who underwent primary radical operation for breast cancer at the Second Department of Surgery, Shinshu University Hospital during five-years from January 1976 to the end of December 1980 were analyzed to investigate for the relationship between biopsy and prognosis. The incisional biopsy group had a significant higher recurrence rate as compared with the no biopsy group, cytology group and the cancer negative group after excisional biopsy. Although the puncture aspiration cytology group did not show significant difference in recurrence rate, an any more than 3 weeks of interval between puncture aspiration cytology and radical surgery associated with a significant high recurrence rate. This suggests that the interval also exerts an unfavorable influence upon prognosis. Puncture aspiration cytology was recognized to be apt to result in distant metastasis than any other biopsy methods and also it is tended to have a higher recurrence rate in scirrhous and mucinous carcinoma of the breast.

Adenocarcinoma, Mucinous↗