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Biomedical subjects

M Fujii

Publications and source records attributed to M Fujii.

At least 397 records · Page 22Linked to original sources
PubMed1996

[Comparative clinical study of adjuvant postoperative chemotherapy (5-FU, Tegafur, 5-FU + MMC) in curatively resected cases of gastric cancer. Study Group on 5-FU Oral Adjuvant Chemotherapy in Gastric Cancer].

A multi-center collaborative study was conducted in curatively resected gastric cancer patients at Stages II and III to compare oral 5-FU (Group A), oral Tegafur (Group B) and i.v. MMC + oral 5-FU (Group C). From May 1982 to April 1985, 1,012 cases were enrolled at 55 institutions. Some 138 (13.8%) were excluded, and 874 were analyzable. In the analysis of background factors, Group B had more cases with tumor of large diameter and advanced Stage. Adverse effects were relatively mild in all groups, and there was no problem in drug tolerance. Five-year survival rate was 67.6%, 62.4% and 68.6% in Groups A, B and C, respectively, reflecting no significant difference among them. It was 85.0%, 83.0% and 81.1% in Stage II and 52.5%, 51.0% and 59.0% in Stage III of Groups A, B and C, respectively. No significant difference was found, but Stage III of Group C showed a slightly higher survival rate. Supportive clinical study will be required to assess the usefulness of MMC as an introduction therapy. We found no difference in efficacy between 5-FU and Tegafur as maintenance therapy. The life-prolongation effect of fluoropyrimidines in comparison with surgery alone should be studied separately.

Adult↗
PubMed1996

[Expression of the small molecular weight matrix metalloproteinase in adenomyosis of the mouse uterus].

The etiology and the pathogenesis of adenomyosis, which is a benign disease featuring ectopic proliferation and invasion of the endometrial stromas and glands into the myometrium, as seen with malignant tumor cells, are still unknown. Adenomyosis induced in mice by intrauterine pituitary isografts was analyzed to study the relationship between adenomyosis and matrix metalloproteinase. Under zymography, adenomyosis showed a gelatiolytic band of 20-30kDa, which was inhibited by EDTA. We then compared matrix metalloproteinase, which is a small protein, with the known pump-1 (MMP7) utilizing RT-PCR and southern blotting hybridization. The PCR product from pump-1 mRNA was clearly detected in both adenomyosis and normal uterus, as in postpartum uterus and kidney in which pump-1 is expressed. These results were confirmed by southern blotting hybridization, and closely resembled the results obtained with RT-PCR. Our study suggests that the small molecular weight matrix metalloproteinase, which is virtually identical to pump-1, may play important roles in adenomyosis at the level of gene transcription, activation, inhibition or otherwise.

Animals↗
PubMed1996

[Prevention of MRSA spread in the neurosurgical field].

We investigated the distribution of MRSA (methicillin-resistant Staphylococcus aureus) on and around six patients with MRSA infection in our neurosurgical ward. All patients had a disturbance of consciousness and had sputum colonization of MRSA. Samples were obtained from 11 sites (patients' hands, attendances' hands, floors, sidetables, bedclothes, chairs, walls, curtains, door knobs, faucets and disposable gloves) in the patients' rooms by the wiping method. High counts of MRSA were detected on horizontal planes such as floors, sidetables and chairs, but MRSA was not detected on vertical planes such as curtains and walls. The reason why MRSA was detected on the horizontal planes was due to a fall of MRSA spread from sputum in the air. These findings indicate that the disinfection of horizontal planes is important for preventing the spread of MRSA. We also evaluated what disinfectant was useful for floor disinfection and concluded that 0.5% chlorhexidine digluconate (Hibitane) and 0.5% benzalkonium chloride (Osvan) were more effective than the other usually-used disinfectants such as alkyldiaminoethyl glycine (Tego-51).

Adult↗
PubMed1996

[A case of lung metastasis from breast cancer successfully treated by FLEP (5-FU leucovorin, etoposide CDDP) combined arterial infusion chemotherapy].

A 33-year-old woman had undergone left mastectomy after diagnosis of breast cancer. One year after operation, multiple lung metastasis was confirmed by chest X-ray and CT scan. The patient received 6 courses of cyclophosphamide, epirubicin, and 5-FU (CAF) combined chemotherapy. However, the lesions were increased and the result of this chemotherapy was judged to be "progressive disease" (PD). A catheter was placed in the thoracic aorta, and FLEP combined intraaortic infusion chemotherapy was performed. The patient received 4 courses of 5-FU (325/mg/m2/day, civ, on day 1-5), leucovorin (30 mg/body/day, iv, on day 1-5), etoposide (60/mg/m2/day, ia, on day 7 and day 21), cisplatin (60/mg/m2/day, ia on day 7 and 21) every 4 weeks. The multiple lung metastasis almost disappeared on chest examination, and found to be less than 1 cm in diameter on CT scan. This result suggests FLEP combined chemotherapy is effective as a second-line treatment of recurrent breast cancer.

Adult↗
PubMed1996

[Relationship between SPECT and pathological alterations in Alzheimer's disease--a study of a case with left-hemisphere dominant lesions].

123I-IMP SPECT (SPECT) has been widely used in clinical neuropsychiatry for establishing the clinical diagnosis, and evaluating the course of the disease. However, little is known about the significance of alterations in SPECT. In this paper, we present comparative study between alterations in SPECT and neuropathological findings in the case of Alzheimer's disease (AD). The patient, a 59-year-old female, began to show memory disturbance and the left hemisphere disturbances, non-fluent aphasia, but right hemisphere disturbances, constructional apraxia, visuo-spatial dysfunctions were not notable at the early stage. The neuroimaging also revealed left-side dominant cerebral atrophy in MRI and left-side dominant hypoactive regions in SPECT (especially in parietal lobe). Memory disturbance and non-fluent aphasia gradually progressed after admission. Then, mirror phenomenon and Bálint's syndrome appeared at the age of 63 years. In the advanced stage, hypoactive regions in SPECT were expanded into temporal and frontal areas. The laterality observed at the early stage became unremarkable. The patient died from heart failure at 64 years. Pathological diagnosis was AD. Eleven ROI (region of interests) were determined on each hemisphere in transverse SPECT image. We calculated ROI% (each ROI count/ROI count at central cerebellum). Neuronal cell count (NCC) and amyloid beta protein deposited areas (BDA) were estimated using 3 serial sections stained with Nissl's method and immunostained for amyloid using monoclonal antibody raised against synthetic A beta, mcAb 90/12. Digitized images based on photographs were analyzed with NIH-image 1.45. NCC decreased in number in frontal, temporal, and parietal lobes. Significant asymmetrical reduction of NCC (lt. < rt.) was observed in orbital, superior temporal and angular gyri (p < 0.01). BDA in superior parietal lobule, superior temporal gyrus and superior, middle, inferior frontal gyri were larger than those in precentral gyrus and visual cortex. Asymmetry of BDA (lt. > rt.) was significant in middle temporal gyrus (p < 0.01). ROI% at the early stage was correlated with corresponding NCC (r = 0.49, p < 0.05) and BDA (r = -0.55, p < 0.01), but at the advanced stage was not significantly correlated with corresponding NCC (r = 0.26) and BDA (r = -0.20). It is evident that SPECT shows good correlation with clinical features and pathological alterations during the course of AD. Our observations imply that the changes in SPECT usually precede the appearance of the clinical symptoms. SPECT is very sensitive in detecting the functional decline in certain regions of the CNS. In the case of AD, the hypoactive regions in SPECT at the early stage may indicate functional decline of the neuronal cells, and at the advanced stage, these may indicate the degree of pathological changes, especially neuronal loss and amyloid beta protein deposition.

Alzheimer Disease↗
PubMed1996

[Combination chemotherapy with 5-FU and CDDP or CDDP analog for head and neck cancer].

Combination chemotherapy with CDDP and 5-FU is one of the effective regimens for head and neck cancer. We studied the difference in the effects and adverse effects between two kinds of schedules of CDDP administration for CDDP-5-FU combination chemotherapy. For 13 patients, CDDP was administered on 5 consecutive days from day 1 to day 5 at a daily dose of 16 mg/m2 (Regimen A). For 14 patients CDDP was administered 80 mg on day 1 (Regimen B). 5-FU was administered 700 mg/m2/ day as a continuous drip infusion for 120 hours from day 1 to day 5. For regimen A, the response rate was 77%; for regimen B, it was 64%. The pattern of adverse effects showed a difference. Regimen B was more toxic for renal function than regimen A. But regimen A showed toxicity for bone marrow function. Acute phase nausea and vomit appeared more frequently in regimen B. The difference in the adverse effect pattern, which depends on the schedule of CDDP administration, seems important in order to apply this regimen for head and neck cancer patients safely. The schedule of CDDP administration should be changes depending on the renal and bone marrow function of patients. In order to evaluate the efficacy of UFT as adjuvant chemotherapy, UFT was administered p.o. to patients with maxillary sinus carcinoma for more than one year after definitive treatment with surgery or radiotherapy. Fifteen patients with UFT adjuvant chemotherapy showed significantly better survival rates than patients without adjuvant chemotherapy. We also studied adjuvant chemotherapy with CBDCA and FT for patients with advanced head and neck cancer. Administration with UFT (600 mg/day) from day 1 to day 14 with CBDCA 350 mg/m2 at day 7 was repeated more than twice. This regimen showed low toxicity and better survival for nasopharyngeal cancer patients. More clinical trials with this regimen for adjuvant chemotherapy are needed.

Adolescent↗
PubMed1996

[Prognostic factors of nasopharyngeal carcinoma treated by radiotherapy].

This study was a retrospective analysis of 82 patients with histologically confirmed nasopharyngeal carcinoma, who were treated at Keio University Hospital from March 1983 to March 1993. We studied all cases(62% of them were stage IV) with regard to their prognostic factors and chronic side effects induced by radiation. All patients were received extended-field radiotherapy from the base of the skull to the supraclavicular lymph node area. The five- and ten-year overall survival rates for the entire group were 59% and 49%, respectively. Three stage I patients were alive without recurrence or metastases for more than 5 years. The ten-year survival rate stage II-III for patients (23 patients) was 78%, and for stage IV (56 patients) 37%. The five-year survival rate of patients in T2-3 group without lymph node metastasis was 88%, while it was reduced to 55% for patients with metastasis. The prognosis of T4 patients was very poor: their five-year survival rate was 37% with lymph node metastasis, and 35%, without lymph node metastasis. Patients under 46 years old showed an increased survival rate compared with patients over 46 years old. Patients who completed less than 52 days of radiation therapy found to have a better prognosis than those receiving radiation for a longer period. Our multivariate analysis indicated that age, radiation period and N-factor were statistically significant in influencing prognosis. Hearing loss occurred relatively high with 20% of cumulative incidence in our study, probably because they received radiation therapy with the extended field including bilateral middle and inner ear. Extended-field radiotherapy for patients with nasopharyngeal carcinoma might contribute to improving their cure-rate, and precise radiation planning is warranted to avoid the late complications such as hearing loss.

Adenocarcinoma↗
PubMed1996

[Eosinophilic pneumonia presenting as a mass shadow].

A 35-year-old man underwent routine chest roentgenography and a mass shadow was seen in the left lung field. Examination of a transbronchial lung biopsy specimen revealed that many eosinophils had infiltrated under the bronchial mucosa and into the alveolar septum. The total serum IgE concentration was high, and skin tests with Aspergillus antigen and serum precipitating antibodies against Aspergillus were positive. The mass lesion disappeared without any therapy, and a cystic lesion remained. Mediators released from eosinophils were thought to have damaged the lung tissue. We should have administrated corticosteroids as soon as possible.

Adult↗
PubMed1995

Expression of the human cGMP-dependent protein kinase II gene is lost upon introduction of SV40 T antigen or immortalization in human cells.

We have cloned a human cGMP-dependent protein kinase type II cDNA to examine its gene expression in terms of cellular senescence and/or immortalization. The genetic locus was mapped to band 4q21 by FISH. Northern blot analysis revealed that expression of the type II gene was markedly decreased or lost in mortal or immortal human fibroblasts producing SV40 T antigen. Also in various immortalized cell lines tested, the gene was not expressed. In normal diploid fibroblasts, the gene was constitutively expressed during cell-cycle and population doubling levels (PDLs).

Amino Acid Sequence↗
PubMed1995

Inhibitors of cGMP-dependent protein kinase block senescence induced by inactivation of T antigen in SV40-transformed immortal human fibroblasts.

Immortal human fibroblasts isolated following transfection with thermolabile simian virus 40 T antigen lost division potential upon shift up in temperature due to heat inactivation of the antigen. Such cells showed a concomitant change in the distribution of a mortality marker, mortalin, from a juxtanuclear cap like distribution of immortal cells to a uniform cytosolic distribution of mortal cells. We made an attempt to modulate the above inducible system of cellular senescence using various protein kinase inhibitors. Among the indolocarbazole type inhibitors tested, only KT5823, defined as a specific inhibitor of cGMP-dependent protein kinase, blocked the loss of division potential as determined by cell growth and colony forming ability. This inhibitor also prevented the above change in mortalin distribution due to temperature shift. In addition, the isoquinoline sulfonamide derivatives H8, H9, H88 and H89, all shown to inhibit cGMP-dependent protein kinase, suppressed the senescence. Inhibitors specific to other types of protein kinases, protein phosphatases or tyrosine kinases tested had no effect. Since there was no difference between the effective and non-effective inhibitors in their effects on cell cycle progression, cell cycle arrest by itself cannot account for the above phenomenon. These results suggest that a signaling pathway possibly mediated by cGMP-dependent protein kinase is involved in the induction of cellular senescence.

Alkaloids↗
PubMed1995

Iron-ligand structure and iron redox property of nitric oxide reductase cytochrome P450nor from Fusarium oxysporum: relevance to its NO reduction activity.

We studied the nitric oxide reductase, cytochrome P450nor, purified from a denitrifying fungus Fusarium oxysporum with electron paramagnetic resonance spectral and redox potential measurements. The EPR spectral features of P450nor in the ferric resting, the ferric cyanide-bound, and the ferrous NO-bound forms were the same as the corresponding ones of other general P450s such as Pseudomonas putida P450cam. In contrast, the metyrapone complex of ferric P450nor gave an EPR spectrum with significantly different g values from that of P450cam. The EPR results were explained in terms of similarity in the immediate configuration of the S(-)-Fe-ligand (H2O, CN-, NO) structure between P450nor and P450cam but a structural difference at the heme distal pocket, especially in the substrate binding domain; P450cam has a camphor binding domain, while P450nor does not. In spite of the same S(-)-Fe-H2O configuration, the redox potential of P450nor in the ferric/ferrous couple was measured to be -307 mV, which is much lower than those of the camphor-bound (-140 mV) and -free (-250 mV) P450cam. The lower redox potential could be attributable to the different electrostatic interaction of the heme with its surroundings; e.g., the heme environment of P450nor is charged either more negatively or less positively than P450cam.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding Sites↗
PubMed1995

Identification of the Tax interaction region of serum response factor that mediates the aberrant induction of immediate early genes through CArG boxes by HTLV-I Tax.

Tax of human T-cell leukemia virus type I (HTLV-I) activates transcription at a CArG box of various immediate early genes such as the proto-oncogene c-fos. To do this, Tax does not directly bind to the CArG box, but instead binds to the CArG binding factor SRF. In this study, we investigated the domain of SRF required for the activation by Tax and studied the role of this domain on transcriptional regulation at the CArG box. Using a fusion protein of SRF with a yeast transcription factor GAL4, the 14 amino acid (aa) portion (aa 422-435) of SRF was identified as the domain required for Tax activation [Tax-responsive region of SRF (TRRS)]. By means of a two hybrid system, we showed that TRRS was essential for the interaction of SRF with Tax in vivo. The over-expression of SRF with a deletion of TRRS inhibited the Tax activation at the CArG box. Thus, TRRS is the domain of SRF that is essential for Tax activation at the CArG box. Unlike to Tax activation, TRRS was not required for TPA (12-o-tetradecanoylphobol-13-acetate) induction at the CArG box, but a TRRS deletion enhanced the basal activity at the CArG box both under serum-starved and TPA-stimulated conditions. These results suggest that TRRS negatively regulates the transcriptional activation function of SRF, and consequently contributes to the low basal activity at the CArG box before TPA induction.

Amino Acid Sequence↗
PubMed1995

Spectroscopic and kinetic studies on reaction of cytochrome P450nor with nitric oxide. Implication for its nitric oxide reduction mechanism.

Cytochrome P450 purified from Fusarium oxysporum (P450nor) is a unique heme enzyme that catalyzes the reduction of nitric oxide to nitrous oxide with electrons directly transferred from NADH (2NO + NADH + H+--> N2O + H2O + NAD+). We studied the reaction of P450nor with NO and NADH using stopped-flow rapid scan and low temperature spectroscopic methods. The NO ligand can bind to the ferric enzyme to form the stable NO bound complex, P450nor(Fe3+NO). Reduction of P450nor(Fe3+NO) with NADH yielded an intermediate, which transiently formed (tau = approximately 100 ms) and spontaneously decomposed to the Fe3+ state. The optical absorption spectrum of the intermediate was different from that of P450nor(Fe2+NO), which was formed by either a one-electron reduction of P450nor(Fe3+NO) with Na2S2O4 or NO binding to P450nor(Fe2+). On the basis of these observations, we suggested that the intermediate is presumably a two-electron reduced product of P450nor(Fe3+NO) by NADH, formally the (Fe3+NO)2-complex. We determined the rate constants of these reactions at 10 degrees C for the NO binding to P450nor(Fe3+) (2.6 x 10(7) M-1 s-1), the NADH reduction of P450nor(Fe3+NO) (0.9 x 10(6) M-1 s-1), and the spontaneous decomposition of the intermediate (0.027 s-1). In these kinetic measurements, it was found that the former two processes are fast enough, while the latter is extremely slow, compared with the fast turnover of the catalytic reaction (1200 s-1 at 10 degrees C), which we measured by monitoring the NADH consumption. Therefore, we suggested that in the catalytic cycle, decomposition of the intermediate is fairly accelerated by free NO, resulting in such a fast turnover. On the basis of several lines of the spectroscopic and the kinetic evidence, we proposed a possible mechanism of the NO reduction by P450nor.

Cytochrome P-450 Enzyme System↗