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Biomedical subjects

K Chiba

Publications and source records attributed to K Chiba.

At least 91 records · Page 5Linked to original sources
PubMed2000

No toxicity caused by organ accumulation of CPT-11 on multiple injections under clinical regimens in rats.

We investigated the accumulation of CPT-11 and its metabolite (SN-38) in various organs and toxicities on multiple injections of CPT-11 under clinical regimens in SD rats. CPT-11 (16.7 mg/kg equivalent to 100 mg/m2) was administered intravenously by a single injection, or by multiple injections in 1 course (once a week for three consecutive weeks) or 3 courses (1 course repeated 3 times at intervals of 2 weeks). There was no tendency for CPT-11 and SN-38 to accumulate in any organs regardless of the number of injections. Treatment-related changes were not observed in the general condition, body weight, hematology, biochemistry, and organ weights. Histopathological changes induced by CPT-11 were not persistent and the rats made a rapid recovery after the administrations. From these results, it is suggested that there is no toxicity caused by accumulation of CPT-11 and its active metabolite, SN-38, in organs under clinical regimens in rats.

Animals↗
PubMed2000

Comedogenicity of squalene monohydroperoxide in the skin after topical application.

The comedogenicity of squalene peroxides was examined on the rabbit ear skin after topical application of squalene-monohydroperoxide (Sq-OOH), the initial product when squalene was irradiated with UV-A. Since comedogenic products from UV-irradiated squalene were extracted with methanol solution, we isolated Sq-OOH by reverse-phased HPLC with a methanol mobile phase solvent. The degree of comedogenic reaction induced by Sq-OOH was higher than that of well-known comedogenic cosmetic ingredients. Unlike two other mono-peroxides, tert-butyl hydroperoxide and cumene-mono-hydroperoxide, Sq-OOH induced comedo-formation in the rabbit ear skin. However, the comedogenicity of reduced Sq-OOH, squalene-hydroxide (Sq-OH) and squalene itself was lower than that of Sq-OOH. These results indicate that Sq-OOH is a potent comedogenic mono-hydroperoxide chemical to rabbit skin.

Acne Vulgaris↗
PubMed2000

[The difficulty of urethral anastomosis in sigmoid neobladder--the role of preoperative X-ray of an air-contrast barium enema].

BACKGROUND: Sigmoid neobladder (Reddy method) is one of the representative neobladder after radical cystectomy. Occasionally we experienced difficulty on urethral anastomosis in sigmoid neobladder. Here we investigated preoperative X-ray of air-contrast barium enema and clarified what type could be easily anastomosed in sigmoid neobladder. MATERIAL AND METHODS: We performed five cases of total cystectomy with sigmoid neobladder replacement. Of the five, we can easily make a urethral anastomsis in three cases but not easily in other two cases. We investigated sigmoid colon length, it's internal diameter, it's form and it's mobility that was substituted for elevation level of rectosigmoid using preoperative X-ray of air-contrast barium enema. We also studied seventy five cases of X-ray of air-contrast barium enema who visited our hospital with various complaints such as lower abdominal pain. RESULTS: The length of three cases with easily anastomosed were 45.7 cm in diameter other two cases 33.5 cm in diameter.(over all 47.5 cm) The internal diameter were 49 mm and 33.5 mm respectively.(over all 44.4 mm) It was considered that Reddy method was indicated who had at least averaged sigmoid colon length and internal size. Sigmoid colon form were classified into 3 groups (type N. type l and others). There were no difference on colon length regarding sigmoid form, but others was considered to be improper form because significant difference was observed between type N and others in internal diameter. Three cases with easily anastomosed demonstrated a positive correlation of the elevation of the sigmoid colon over promontorium in the air contrast barium enema, other two cases negative. The elevation cases of the sigmoid colon in X-ray of air contrast barium enema had long sigmoid colon than other types.(p < 0.0001) Tha mean length of them was 51.6 cm in diameter. CONCLUSION: Sigmoid neobladder was at least indicated in men who had averaged sigmoid colon length. The sigmoid colon elevation sign in X-ray of air contrast barium enema did not require the measurement of sigmoid colon length and that sign implied good indication for sigmoid neobladder.

Adult↗
PubMed2000

[beta-thalassemia minor diagnosed in a patient with chronic myelogenous leukemia during hydroxyurea therapy].

A 55-year-old man was admitted to our hospital because of leukocytosis and microcytic anemia with hypochromia, target cells, and increased levels of hemoglobin A2 and hemoglobin F. The results of a gene analysis yielded a diagnosis of chronic myelogenous leukemia and beta-thalassemia minor. A gradual increase in hemoglobin was observed during hydroxyurea therapy, which was performed over a 12-week period. This increment appeared to be due to suppressed production of myeloid cells. It was been reported that hydroxyurea increases total hemoglobin due to increased hemoglobin F synthesis in patients with beta-thalassemia. However, hydroxyurea had no clear influence on hemoglobin concentration in this case.

Antineoplastic Agents↗
PubMed2000

[Evaluation of varicocele by ultrasonography through a water bag in the supine position].

Recently, ultrasonography has been widely used to evaluate varicocele. However, it is difficult to obtain reproducible scrotal images with a hand probe in the standing position. We, therefore, applied the water bag technique during ultrasonographic examination of the scrotal contents in the supine position. The ultrasonographic images thus obtained were compared with physical findings and scrotal scintigraphic findings. Forty-five varicocele patients diagnosed by palpation and ultrasonography were enrolled in this study. An ultrasonographic examination through a water bag in the supine position has the following advantages 1) it is easy to perform and stable images are obtained, 2) varicoceles that are not palpable can be detected and 3) examinations can be repeated both pre- and postoperatively. Of the 45 patients, 39 and 41 had positive findings on the ultrasonographic images and physical examinations, respectively. Four patients had negative findings on physical examination but positive findings on the ultrasonographic images. Thus, ultrasonographic images through a water bag in the supine position proved to be a useful method of confirming the hemodynamics in varicoceles.

Adolescent↗
PubMed2000

[Treatment of renal cell carcinoma extending into the right atrium with extra-corporeal circulation using high-grade hypothermia: a case report].

A 68-year-old woman underwent surgical treatment for renal cell carcinoma associated with tumor thrombus extending into the right atrium. Although the tumor thrombus reached the level of the right atrium, there were no other apparent metastases. Combination therapy with interferon alfa plus tegafur/uracil (UFT) was attempted with the expectation of reducing the tumor thrombus, but there was no change. Successful management was achieved with right radical nephrectomy, right auriculotomy, and partial cavectomy using cardiopulmonary bypass under high-grade hypothermia. After removal of the tumor and thrombus, blood loss was 13,900 ml during the patient's recovery. She had mild heart failure for about two weeks after the operation, but recovered. She was discharged on the 40th day after the operation. Proper preparation for blood transfusion is the key point of this operation.

Aged↗
PubMed2000

Phenacetin deacetylase activity in human liver microsomes: distribution, kinetics, and chemical inhibition and stimulation.

Microsomal and cytosolic phenacetin deacetylase activities were examined in human liver and kidneys. Kinetic properties of the activities were also studied in human liver microsomes. Phenacetin deacetylase activity was predominantly localized in the liver microsomal fraction. The specific activities of phenacetin deacetylation in liver cytosol and in kidney microsomes and cytosol were all less than 5% of that in liver microsomes. In human liver microsomes, Eadie-Hofstee plots for phenacetin deacetylation were monophasic, indicating a single-enzyme catalytic reaction. The Michaelis-Menten parameters, K(m) and V(max), for the deacetylation were 4.7 mM and 5.54 nmol/min/mg of protein, respectively. The intrinsic clearance, calculated as V(max)/K(m), was 1.18 microl/min/mg of protein. Although the organophosphate bis(4-nitrophenyl)phosphoric acid markedly inhibited the reaction in human liver microsomes, the activity has a tolerance to the treatment of phenylmethylsulfonyl fluoride, a serine hydrolase inhibitor. Prazosin, a peripheral alpha(1)-adrenergic antagonist, noncompetitively inhibited the phenacetin deacetylation with a K(i) value of 19.0 microM. Flutamide, a nonsteroidal androgen receptor antagonist, stimulated the activity by up to 349%. This increase was accompanied by a decrease in the K(m) value and no change in the V(max) value, resulting in an increase in the intrinsic clearance by up to 700% of the control. These results suggest that the phenacetin deacetylase localized in human liver microsomes has not only a catalytic site but also a negative and/or positive modulation site or sites.

Carboxylic Ester Hydrolases↗
PubMed2000

Identification of CYP3A4 as the enzyme involved in the mono-N-dealkylation of disopyramide enantiomers in humans.

To identify which cytochrome P-450 (CYP) isoform(s) are involved in the major pathway of disopyramide (DP) enantiomers metabolism in humans, the in vitro formation of mono-N-desalkyldisopyramide from each DP enantiomer was studied with human liver microsomes and nine recombinant human CYPs. Substrate inhibition showed that SKF 525A and troleandomycin potently suppressed the metabolism of both DP enantiomers with IC50 values for R(-)- and S(+)-DP of <7.3 and <18.9 microM, respectively. In contrast, only weak inhibitory effects (i.e., IC50 > 100 microM) were observed for five other representative CYP isoform substrates [i.e., phenacetin (CYP1A1/2), sparteine (CYP2D6), tolbutamide (CYP2C9), S-mephenytoin (CYP2C19), and p-nitrophenol (CYP2E1)]. Significant correlations (P <.01, r = 0.91) were found between the activities of 11 different human liver microsomes for mono-N-dealkylation of both DP enantiomers and that of 6beta-hydroxylation of testosterone. Conversely, no significant correlations were observed between the catalytic activities for DP enantiomers and those for the O-deethylation of phenacetin, 2-hydroxylation of desipramine, hydroxylation of tolbutamide, and 4'-hydroxylation of S-mephenytoin. Further evidence for involvement of CYP3A P450s was revealed by an anti-human CYP3A serum that inhibited the mono-N-dealkylation of both DP enantiomers and 6beta-hydroxylation of testosterone almost completely (i.e., >90%), whereas it only weakly inhibited (i.e., <15%) CYP1A1/2- or 2C19-mediated reactions. Finally, the recombinant human CYP3A3 and 3A4 showed much greater catalytic activities than seven other isoforms examined (i.e., CYP1A2, 2A6, 2B6, 2C9, 2D6, 2E1, and 3A5) for both DP enantiomers. In conclusion, the metabolism of both DP enantiomers in humans would primarily be catalyzed by CYP3A4, implying that DP may have an interaction potential with other CYP3A substrates and/or inhibitors.

Aged↗
PubMed2000

Treatment with low-dose cytosine arabinoside followed by administration of macrophage colony-stimulating factor prolongs the survival of patients with RAEB, RAEB-T, or leukemic phase myelodysplastic syndrome: a pilot study.

The treatment of patients with aggressive subclasses of myelodysplastic syndrome (MDS) remains a challenge. In an effort to improve the survival of patients with refractory anemia with excess blasts (RAEB), RAEB in transformation (RAEB-t), or acute myelogenous leukemia transformed from MDS (MDS-AML), we conducted a small trial in which 28 such patients were treated with low-dose cytosine arabinoside (LDAraC) followed by administration of macrophage colony-stimulating factor (M-CSF). The overall rate of response to the treatment was 61%, including 39% with a complete response, which is higher than rates obtained in previous studies in which LDAraC alone was administered to patients with MDS. Median survival was 23.5 months in cases of RAEB, 16.7 months in cases of RAEB-t, and 19.7 months in cases of MDS-AML. The overall survival of the study group appeared to be prolonged in comparison with a historical control group of patients treated with LDAraC alone. It is suggested that M-CSF added to the administration of LDAraC plays an active role in the therapy. No therapy-related death occurred. Some unique actions of M-CSF were suggested in this trial. It is concluded that therapy with LDAraC + M-CSF is a useful treatment option for patients with aggressive subclasses of MDS and MDS-AML to provide better response and survival.

Adult↗
PubMed2000

Role of human cytochrome P450 3A4 in metabolism of medroxyprogesterone acetate.

Medroxyprogesterone acetate (MPA) is a drug commonly used in endocrine therapy for advanced or recurrent breast cancer and endometrial cancer. The drug is extensively metabolized in the intestinal mucosa and in the liver. Cytochrome P450s (CYPs) involved in the metabolism of MPA were identified by using human liver microsomes and recombinant human CYPs. In this study, the overall metabolism of MPA was determined as the disappearance of the parent drug from an incubation mixture. The disappearance of MPA in human liver microsomes varied 2.6-fold among the 18 samples studied. The disappearance of MPA in the same panel of 18 human liver microsomes was significantly correlated with triazolam alpha-hydroxylase activity, a marker activity of CYP3A (r = 0.764; P < 0.001). Ketoconazole, an inhibitor of CYP3A4, potently inhibited the disappearance of MPA in 18 human liver microsomes. Anti-CYP3A antibody also inhibited 86% of the disappearance of MPA in human liver microsomes. Although sulfaphenazole (an inhibitor of CYP2C9) and S-mephenytoin (an inhibitor of CYP2C19) partially inhibited the disappearance of MPA, no effect of the anti-CYP2C antibody was observed. The disappearance of MPA did not correlate with either the activity metabolized via CYP2C9 (diclofenac 4'-hydroxylase activity) or the activity metabolized via CYP2C19 (S-mephenytoin 4'-hydroxylase activity). Among the 12 recombinant human CYPs (CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2D6, CYP2E1, CYP3A4, and CYP3A5) studied, only CYP3A4 showed metabolic activity of MPA. These results suggest that CYP3A4 is mainly involved in the overall metabolism of MPA in human liver microsomes.

Animals↗
PubMed2000

[5'-DFUR chemoprophylaxis in superficial bladder cancer. Kanagawa Urology 5'-DFUR Study Group].

5'-Deoxy-5-fluorouridine (5'-DFUR), an oral fluorinated pyrimidine carbamate, is widely used in patients with gastrointestinal and breast cancers because of its effectiveness. However, in bladder cancer, response rates have only been reported in Phase II clinical trials. Therefore, we conducted a prospective randomized trial to investigate chemoprophylactic effect of 5'-DFUR against recurrence of superficial bladder cancer after transurethral bladder tumor resection (TUR-Bt). The subjects were grouped as follows: 1) 5'-DFUR group (n = 31), received 600 mg/day of 5'-DFUR starting 2-3 weeks after TUR-Bt for 2 years; and 2) control group (n = 31) received no 5'-DFUR. Although there was no significant difference between groups, the cumulative recurrence rates was more favorable in the 5'-DFUR group (p = 0.256) than in the controls. Results according to cancer factors showed that, in patients with G2 based on grading, those in the 5'-DFUR group tended to have a lower recurrence rate than the control group (p = 0.070). There was a 40% incidence of adverse drug reactions (12/30 patients), primarily slight gastrointestinal symptoms which disappeared or improved with drug discontinuation. The results of the present study suggest that 5'-DFUR might be the choice of treatment to prevent recurrence of superficial bladder cancer.

Adult↗
PubMed2000

Bioactivation of tegafur to 5-fluorouracil is catalyzed by cytochrome P-450 2A6 in human liver microsomes in vitro.

Tegafur is a prodrug of 5-fluorouracil (5-FU) consisting of a new class of oral chemotherapeutic agents, tegafur/uracil and S-1, which are classified as dihydropyrimidine dehydrogenase inhibitory fluoropyrimidines. It is bioactivated to 5-FU via 5'-hydroxylation mediated by cytochrome P-450 (CYP). However, which isoform(s) of CYP is responsible for the bioactivation process of tegafur remains unclear. The purpose of the present study was to identify the human CYP isoform(s) involved in the metabolic activation of tegafur using human liver microsomes and cDNA-expressed human CYPs. The formation of 5-FU from tegafur in human liver microsomes showed biphase kinetics with Km and Vmax values for the high-affinity component of 0.43 +/- 0.05 mM and 4.02 +/- 1.70 nmol/mg/min (mean +/- SD, n = 4), respectively. In the correlation study using a panel of 10 human liver microsomes, the formation of 5-FU from tegafur showed a significant correlation (r = 0.98; P < 0.001) with coumarin 7-hydroxylation, a marker activity of CYP2A6. In addition, a specific substrate of CYP2A6 and anti-CYP2A6 antibody inhibited the formation of 5-FU by 90% in human liver microsomes. Moreover, cDNA-expressed CYP2A6 showed the highest activity for the formation of 5-FU among 10 cDNA-expressed CYPs, with a Km value similar to that found for the high-affinity component in human liver microsomes. These findings clearly suggest that CYP2A6 is a principal enzyme responsible for the bioactivation process of tegafur in human liver microsomes. However, to what extent the bioactivation of tegafur by CYP2A6 accounts for the formation of 5-FU in vivo remains unclear, because the formation of 5-FU from tegafur is also catalyzed by the soluble fraction of a 100,000 x g supernatant and also derived from spontaneous degradation of tegafur.

Antimetabolites, Antineoplastic↗
PubMed2000

[A case of urachal abscess mimicking a tumor in the retrovesical space].

A 14-year-old girl was admitted to our hospital because of umbilical erythema and discharge. She had had an appendectomy at the age of twelve. Abdominal ultrasonography and cystoscopy revealed a large tumor-like mass at the posterior wall of the bladder. Computed tomography and magnetic resonance imaging revealed urachal sinus. The diagnosis of urachal abscess had been confirmed and conservative treatment had been continued by drainage via umbilicus and the administration of antibiotics. Total excision of the urachus was performed about one month later because the bladder mass was not reduced. Pathological findings revealed an inflammatory thickened wall of the urachus and no evidence of malignancy. We report this rare case of urachal abscess with a large mass in the retrovesical space.

Abscess↗
PubMed2000

[Brain metastasis of bladder carcinoma after total cystectomy: a case report].

A 74-year-old woman underwent total cystectomy with ureterostomy on March 1993 on a diagnosis of advanced bladder cancer. The pathological diagnosis was transitional carcinoma grade 3, pT3a pN0 pV1, pL2. Two courses of adjuvant chemotherapy with CDDP and MTX were added. Three years and 3 months later, she began to suffer from amnesia and hemiparalysis on her left side. Brain MRI examination revealed a solid tumor, 4 x 4 x 3 cm in size, in the right frontal lobe of the cerebrum. No other metastatic lesions were found. She underwent surgical resection of the tumor and subsequent irradiation to right frontal lobe in the cerebrum. Pathological examination confirmed its origin of bladder cancer. She has been enjoying a disease-free life for 3 years with minimal neurological symptoms.

Aged↗
PubMed2000

[A case of retroperitoneal teratoma difficult to distinguish from adrenal myelolipoma].

A 59-year-old man presented to our hospital suspected of having cholelithiasis. Computed tomography (CT) scan revealed a left retroperitoneal solid tumor cephalad to the kidney, 7 x 8 x 9 cm in size with mostly a fatty density area and focal calcification. Magnetic resonance imaging (MRI) on T1 and T2 weighted images showed a high intensity mass. Angiography revealed the hypovascular tumor. Although we had suspected it to be an adrenal myelolipoma, tumorectomy was performed because of its size. Pathological diagnosis was mature teratoma. Although retroperitoneal teratoma contains fas, cyst, soft tissue and calcification, the proportion of fat in the tumor is usually less than that of adrenal myelolipoma. In our case, the tumor contained more fat than the 'typical' retroperitoneal teratoma, which led to the misdiagnosis.

Adrenal Gland Neoplasms↗