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Biomedical subjects

H Minami

Publications and source records attributed to H Minami.

At least 55 records · Page 3Linked to original sources
PubMed2000

Dose-escalation study of CHOP with or without prophylactic G-CSF in aggressive non-Hodgkin's lymphoma.

BACKGROUND: CHOP is accepted as the gold standard for first line chemotherapy of aggressive non-Hodgkin's lymphoma (NHL). A dose-escalation study of CHOP was conducted to determine the maximal tolerated dose (MTD) and toxicity profile of CHOP at three-week intervals with or without prophylactic recombinant human granulocyte colony-stimulating factor (rHuG-CSF) in patients with aggressive NHL. PATIENTS AND METHODS: The doses of drugs were escalated from 50 mg/m2 to 70 mg/m2 for doxorubicin and from 750 mg/m2 to 2250 mg/m2 for cyclophosphamide, with conventional doses of vincristine and oral prednisolone. After the MTD was determined without rHuG-CSF, dose escalation was conducted with prophylactic rHuG-CSF. RESULTS: Thirty-three patients with NHL were enrolled into the study. The MTD without prophylactic rHuG-CSF was 70 mg/m2 of doxorubicin and 1250 mg/m2 of cyclophosphamide, with neutropenia as a dose-limiting toxicity. The MTD with prophylactic rHuG-CSF was 70 mg/m2 of doxorubicin and 2250 mg/m2 of cyclophosphamide. The overall response rate was 100% (76% complete response and 24% partial response). Progression-free survival and overall survival at five years were 45% and 66%, respectively. CONCLUSIONS: Significant dose escalation of doxorubicin and cyclophosphamide was feasible with prophylactic rHuG-CSF. The efficacy of dose-escalated CHOP should be compared with that of standard CHOP.

Adolescent↗
PubMed2000

Compound heterozygous group A xeroderma pigmentosum patient with a novel mutation and an inherited reciprocal translocation.

The severity of neurological abnormalities in Japanese group A xeroderma pigmentosum (XP-A) patients correlates with the sites of non-sense mutation in the XP-A gene. We describe a patient who presented with a more severe photosensitivity and neurological abnormality than those in typical Japanese XP-A patients with a splicing mutation in intron 3. The patient was compound heterozygous for the splicing mutation in intron 3, which resulted in formation of a non-sense codon in exon 4, and a novel non-sense mutation at codon 208 in exon 5, a C to T transition creating a stop codon TAG. Although the combination of these mutations might have been thought to cause only mild neurological signs, the longer truncated XP-A proteins than those of typical XP-A patients may have resulted in severe neurological symptoms. This phenomenon may be explained by a translocation of chromosome (1;10)(q25.3;q22.3) inherited from his father.

Adult↗
PubMed2000

Two new meliacarpinins from the roots of Melia azedarach.

Two new azadirachtin-type limonoids, 1-methacrylyl-3-acetyl-11-methoxymeliacarpinin (1) and 1-(2-methylpropanoyl)-3-acetyl-11-methoxymeliacarpinin (2), together with the known compounds, meliacarpinin D (3), melianin B (4) and 2 beta,3 beta-dihydroxy-5 alpha-pregn-17(20)-(Z)-en-16-one (5), were isolated from the roots of Melia azedarach. The structures of 1 and 2 were elucidated by analysis of spectroscopic data and comparison of their NMR data with those of 3. Compounds 1 and 5 exhibited significant activity in the brine shrimp lethality test (BST).

Animals↗
PubMed2000

Three new sesquiterpene lactones from the pericarps of Illicium merrillianum.

Structures of three new sesquiterpene lactones 1-3, isolated from the pericarps of Illicium merrillianum, have been assigned as 14-O-benzoylfloridanolide, 2,10-epoxy-3-dehydroxypseudoanisatin and 7-O-methylpseudomajucin on the basis of spectroscopic data and chemical transformation. The structure of 2, having an ether linkage between C-2 and C-10, has been confirmed by X-ray crystallographic analysis.

China↗
PubMed2000

Lung cancer in women: sex-associated differences in survival of patients undergoing resection for lung cancer.

STUDY OBJECTIVES: The aim of this study was to analyze various characteristics and survival in female patients treated surgically for lung cancer. DESIGN: Retrospective clinical study. PATIENTS: From 1,242 consecutive cases of primary non-small cell lung cancer treated with pulmonary resection between June 1984 and December 1998, 337 female patients (27.1%) were chosen. RESULTS: Female patients had the following characteristics: a significantly younger age at onset (62.5 +/- 0.56 years vs 64.1 +/- 0.31 years for men), a higher frequency of adenocarcinoma (86.0% vs 48.3% for men), and smaller tumors (32.7 mm vs 38.3 mm in diameter for men). Peripheral tumors were significantly more common in women than men (71.8% vs 50.6%, respectively). Among 686 patients with a history of smoking, the women smoked significantly less often (12.8% vs 91.4% for men). Complete resection was achieved significantly less often in women (79.6% vs 85.2% for men); however, women having complete resection survived significantly longer than their male counterparts. Women with a postoperative negative carcinoembryonic antigen (CEA) had a significantly better prognosis than men; however, women with a postoperative positive CEA did not. Women > or = 60 years old survived significantly longer than their male counterparts, while women < 60 years old did not. CONCLUSIONS: Once the tumor was resected completely, women survived longer, partly due to the influence of life expectancy. However, the incidence of malignant effusion was higher and the rate of complete resection was lower in women.

Carcinoembryonic Antigen↗
PubMed2000

Localization of mRNAs for novel, atypical as well as conventional protein kinase C (PKC) isoforms in the brain of developing and mature rats.

Using in situ hybridization histochemistry, the localization of mRNAs for 10 isoforms of protein kinase C (PKC) in the rat brain was studied at embryonic and postnatal stages. In the embryonic brain, the gene expression was positive only for PKCepsilon, mu, lambda, and zeta with the former three more evident: The expression for PKCmu and lambda in the ventricular germinal zone and that for PKCepsilon, zeta, and lambda in the mantle zone. In the postnatal brain, the expression for PKCdelta, eta, and theta was detected differentially in a few circumscribed loci such as the thalamus, the habenula, the septum, and the cerebellar granule cells, whereas that for the other isoforms was seen widely in various loci of the gray matter with different intensity. The expression in the cerebellar external granule cell layer was positive only for PKCbeta (betaI and betaII), mu, and lambda with that for PKCbeta confined to its inner zone. There is a general tendency for all PKC isoforms that the expression levels reach at peaks in early postnatal brain and decreases more or less in adult specimens. This is the first report on the spatio-temporal heterogeneity in the gene expression for the whole members of PKC family in the brain throughout development, especially at embryonic days.

Aging↗
PubMed2000

[Surgical treatment of intracardiac tumors in 25 patients].

For most intracardiac tumors, operation is the only means of therapy. In our institute, we have aggressively performed operation for intracardiac tumors regardless of histological type because resection for tumor had a beneficial effect on the hemodynamics with congestive heart failure. Twenty-five cases of cardiac tumors were operated upon from 1980 through 1998. The follow-up period ranged from 2 months to 19 years. The histological diagnoses of the tumors were as follows: benign tumors 24 (myxoma 21, papillary fibroelastoma 1, fibroma 1, angiomyolipoma 1) and malignant tumor (angiosarcoma 1). There was one hospital death in this series. In the New York Heart Association classification, the cardiac performances of intracardiac benign tumors after operation were Class I or II. The results of surgical treatment of intracardiac benign tumors were satisfactory both in short-term and in long-term. On the other hand the long term result of malignant tumor was extremely poor. A patient with angiosarcoma died 8 months later due to bone metastasis.

Aged↗
PubMed2000

[Evidence for Taxotere treatment with solid tumors].

Evidence based medicine is essential to further develop the state of the art for cancer treatments. We introduce the levels of evidence for Taxotere treatment against various solid tumors. Most evidence for Taxotere therapy was produced in other countries. However, in Japan we have some data from phase II clinical trials for the approval of Taxotere. We review these domestic results, which reveal its usefulness and toxicity in Japanese patients. In addition, we analyze the evidence from the data of clinical trials of Taxotere conducted by investigators in the USA/Europe. Japanese physicians or academies must build a consensus for the application of Taxotere to Japanese patients with solid tumors.

Antineoplastic Agents, Phytogenic↗
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

[Accelerated titration design].

To reduce the number of patients treated at low and biologically inactive doses in phase I trials of anticancer agents, attempts to decrease the number of patients per dose level and to conduct a larger dose escalation have been made. Among them, accelerated titration designs were proposed and evaluated by simulation; designs 2 and 4 were reported to be acceptable (J Natl Cancer Inst 89: 1138-1147, 1997). Both designs 2 and 4 included only one patient per cohort during the initial accelerated phase. Dosage steps for the accelerated phase were defined using the modified Fibonacci method for design 2 and 100% escalation for design 4, respectively. The accelerated phase continued until one patient experienced dose-limiting toxicity or two patients experienced grade 2 toxicities. Dose escalation was conducted based on the information from the first course in design 2 and from the first three courses in design 4. In the simulation, both designs successfully reduced the total number of patients and the number of undertreated patients without increasing the number of overtreated patients. However, the safety of design 4 was assured as long as all patients received three courses of chemotherapy, which is unusual in phase I studies in Japan. Decision-making on dose escalation based on the information on toxicity in three courses might be cumbersome. Therefore, in Japan, design 2 would be recommended among the proposed accelerated designs. The performance of the design should be investigated by applying it to actual phase I studies and by evaluating the number of undertreated and overtreated patients.

Antineoplastic Agents↗
PubMed2000

Study of dose escalation and sequence switching of administration of the combination of docetaxel and doxorubicin in advanced breast cancer.

The objectives of the present study were to evaluate whether a schedule-dependent pharmacokinetic and/or pharmacodynamic interaction exists between two sequences of docetaxel and doxorubicin administration and to determine the maximal tolerated dose (MTD) of this combination. Patients with chemotherapy-naïve metastatic or recurrent advanced breast cancer were enrolled. In the crossover design, tandem dose escalation of docetaxel and doxorubicin was performed. Docetaxel, in doses ranging from 50-70 mg/m2, was administered for 1 h by drip infusion either just before or after a 5-min bolus i.v. injection of doxorubicin at dosages from 40-50 mg/ m2. The sequence of drug administration was switched after the first course in each patient, and the sequence of drug administration thereafter depended on the patient's choice. Twenty-five patients were initially assessable for toxicity. The MTD in the sequence of doxorubicin after docetaxel was 40 and 50 mg/m2, respectively, with the dose-limiting toxicity of neutropenia. On the other hand, the MTD of the sequence of docetaxel after doxorubicin was 70 and 50 mg/m2, respectively. The dose-limiting toxicities in this sequence were neutropenia and diarrhea. Duration of grade 4 neutropenia in the sequence of docetaxel followed by doxorubicin was significantly longer than that in the alternate sequence (P = 0.0062). However, there was no difference in pharmacokinetic parameters of docetaxel, doxorubicin, and doxorubicinol between the two sequences. The sequence of 50 mg/m2 doxorubicin followed by 60 mg/m2 docetaxel is recommended for subsequent clinical trials for practical reasons.

Adult↗
PubMed2000

Multi-institutional validation study of carboplatin dosing formula using adjusted serum creatinine level.

Creatinine clearance (Ccr) is widely used as a practical substitute for glomerular filtration rate (GFR) in the Calvert formula: carboplatin dose (mg) = target area under the concentration versus time curve (AUC, mg ml(-1) min) x [GFR (ml min(-1)) + 25]. However, it causes systematic overdosing when the creatinine levels are measured by an enzymatic peroxidase-antiperoxidase method (PAP-Cr). We previously suggested an amended dosing formula to adjust this overdosing: carboplatin dose (mg) = AUC (mg ml(-1) min) x [adjusted Ccr (ml min(-1)) + 25], where the Ccr was adjusted by adding 0.2 (mg dl(-1)) to serum PAP-Cr. In this study, we prospectively validated this formula in 55 patients from six institutions. Target AUC ranged from 3 to 7 mg ml(-1) min, and Ccr was measured by 24-h urine collection. Estimation of carboplatin clearance with the amended formula was unbiased [mean prediction error (MPE) +/- SE = 2.9 +/- 3.4%] and acceptably precise [root mean squared error, (RMSE) = 24.7%], whereas the Calvert formula using non-adjusted Ccr overpredicted carboplatin clearance systematically (MPE +/- SE = 24.9 +/- 4.9% and RMSE = 36.1%). The improvement in the bias and precision of the estimation was seen in all of the participating institutions as shown by decrease in the absolute value of MPE and RMSE for each institution. The Chatelut formula also highly overestimated carboplatin clearance when PAP-Cr was used, but the adjustment of PAP-Cr yielded a decrease in MPE by 30.4% and in RMSE by 21.3%. These results confirmed the necessity of adjusting the serum PAP-Cr in carboplatin dosing formulas.

Adult↗
PubMed1999

Lung carcinoma in patients age younger than 30 years.

BACKGROUND: To the authors' knowledge, no study regarding lung carcinoma patients age <30 years has been published. Therefore, this study was undertaken to define the characteristics of lung carcinoma patients age <30 years. METHODS: Information regarding 26 patients with primary lung carcinoma who were age <30 years was obtained from 10 medical institutions and reviewed retrospectively. For comparison, 304 patients age > or = 30 years who were admitted to the First Department of Internal Medicine at Toyama Medical and Pharmaceutical University between 1980-1996 were studied. RESULTS: Among the characteristics observed in the group of lung carcinoma patients age <30 years was a high incidence of female gender, no history of smoking, so-called "low grade malignancy," American Joint Committee on Cancer Stage I disease, and previous surgical resection. In addition, a low incidence of squamous cell carcinoma was noted, and a more favorable prognosis was observed. CONCLUSIONS: The current study noted clinical features that could be defined clearly in lung carcinoma patients age <30 years.

Adolescent↗
PubMed1999

Does pressure antagonize anesthesia? High-pressure stopped-flow study of firefly luciferase and anatomy of initial flash.

The antagonizing effect of high pressure against anesthesia is well known. With purified firefly luciferase, however,. Biophys. J. 60:1309-1314) reported that high pressure did not affect the initial flash intensity. Firefly luciferase emits a burst of light when the substrates luciferin and ATP are added in the presence of O2. The light intensity decays rapidly and the weak light lasts for hours. The initial flash is a transient event and is not in a steady state. The steady state is represented by the slope of the linear part of the integral of the light output. The present study used a high-pressure stopped-flow system to compare the pressure effects on the initial flash intensity and the steady-state light intensity. The flash intensity did not change by the application of hydrostatic pressure in the presence or absence of chloroform or 1-octanol. In contrast, high pressure increased the steady-state light intensity. The application of 12 MPa pressure increased the steady-state light intensity of firefly luciferase inhibited by 5 mM chloroform or 0.7 mM 1-octanol by 19.7% and 18.8%, respectively. When analyzed by the rapid reaction kinetics of the transition state theory, the initial peak intensity represents the total amount of active enzyme and is unrelated to the reaction rate. Anesthetics inhibited the initial flash by unfolding the protein, thereby decreasing the concentration of the active enzyme. Pressure affected the steady-state light intensity by changing the reaction rates.

Anesthesia↗
PubMed1999

Low-grade B-cell lymphoma of mucosa-associated lymphoid tissue in the lung: a report of a case with pleural dissemination.

A 79-year-old man with an abnormal shadow on a chest radiograph was referred to our hospital for further examination. Open lung biopsy revealed numerous nodules on visceral pleura and the tumor, obtained by wedge resection of the left upper lobe of the lung, consisted of centrocyte-like cells and lymphoplasmacytoid cells, expressing CD20 and CD79a. These cells invaded bronchiolar epithelium to form lymphoepithelial lesions. The pleural-based nodules were similarly composed of the same cells as those in the left upper lobe tumor. To our knowledge, pleural dissemination of low grade B-cell lymphoma of mucosa-associated lymphoid tissue has not been reported previously.

Aged↗
PubMed1999

Chemical conversion of vibsanin C to vibsanin E and structure of 3-hydroxyvibsanin E from viburnum awabuki

Vibsanin E (4), a tricyclic vibsane-type diterpene, has been prepared in 50% yield from vibsanin C (2), a seven-membered ring vibsane-type diterpene by reaction with BF3.OEt2 at -78 degrees C. This chemical correlation not only established structure, including absolute configurations, but also has demonstrated a possible biosynthetic route to 4 via 2 derived from vibsanin B (1). The structure of 3-hydroxyvibsanin E (5), another example of a tricyclic seven-membered ring vibsane, isolated from the leaves of Viburnumawabuki, has been established by extensive analyses of 2D NMR data and comparison of its spectral data with those of 4.

Journal Article↗
PubMed1999

Hypoxia potentiates ultraviolet A-induced riboflavin cytotoxicity.

Flavins are thought to be important chromophores for chronic photo-induced skin injury, but the mechanism is not well known. We have reported that the primary cytotoxicity remaining in ultraviolet A-irradiated riboflavin solution is attributable to hydrogen peroxide. Because the dermis is more hypoxic than the atmosphere, we investigated the cytotoxicity of riboflavin solution during and after ultraviolet A irradiation under hypoxia. Riboflavin solution showed stronger cytotoxicity during irradiation under hypoxia than under air. Riboflavin solution that had been irradiated under hypoxia at lower ultraviolet A doses showed stronger cytotoxicity and contained more hydrogen peroxide than solution irradiated under air at the same doses. At higher ultraviolet A doses, however, the cytotoxicity and hydrogen peroxide quantity were similar in riboflavin solutions irradiated under different oxygen conditions. The effect of a singlet oxygen quencher, sodium azide, on the induction of cytotoxicity and production of hydrogen peroxide by ultraviolet A irradiation of riboflavin solution was examined. The presence of sodium azide in the solution during ultraviolet A irradiation suppressed the cytotoxicity and hydrogen peroxide production to similar levels at various ultraviolet A doses regardless of oxygen conditions. At the maximum suppression by sodium azide, hydrogen peroxide production decreased to 10% of the unsuppressed production. About 40% of the oxygen molecules of hydrogen peroxide produced was thought to be derived from oxygen dissolved in the riboflavin solution.

Cell Line↗