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Biomedical subjects

M Fujii

Publications and source records attributed to M Fujii.

At least 235 records · Page 13Linked to original sources
PubMed1999

Effect of freeze-dried soybean curd (tofu) on various bodily functions.

The present study was designed to examine the effect of freeze-dried soybean curd (tofu) on various bodily functions. The dietary experiment consisted of 4 days of a non-prescribed ordinary diet, 10 days of an experimental diet that contained 190 g of meat contributing about 38 g of protein (hereinafter referred to as the "meat period"), and 39 days of an experimental diet that contributed vegetable protein, i.e., freeze-dried tofu, corresponding to the protein that 190 g of meat would provide (hereinafter referred to as the "freeze-dried tofu period"). Three eggs (about 150 g) and 180 ml of cow's milk were prescribed for the daily diet, and staple and other foods were dispensed freely during both the meat and the freeze-dried tofu periods. The results showed that serum cholesterol levels and diastolic blood pressure significantly decreased in the freeze-dried tofu period as compared with the meat period. Freeze-dried tofu was found to be a valuable food for preventing lifestyle-related chronic diseases.

Adult↗
PubMed1999

Using preoperative UFT to predict sensitivity to fluoropyrimidines in colorectal cancer.

This study was designed to determine if histopathologic evaluation of patients with resectable colorectal cancer following preoperative chemotherapy with uracil and tegafur with a molar ratio of 4:1 (UFT) could predict chemosensitivity to postoperative fluoropyrimidines to prevent recurrence of disease. In this prospective randomized study involving 152 colorectal cancer patients, UFT 600 mg/day was administered for 10 days prior to surgery. Histopathology of the resected tumor was assessed, including the amount of necrosis or disappearance of tumor, and patients were thereafter stratified into two groups according to tumor response to preoperative therapy--grade > or = 2 (sensitive) vs those with grade < or = 1B (not sensitive). The patients were then randomly assigned to postoperative adjuvant UFT (400 mg/day for 12 months) or no treatment. At the time of this evaluation, the mean total preoperative UFT dose per patient was 7.76 g +/- 3.27 g. Thirteen patients were considered ineligible; therefore, 139 patients were included in the analysis. Stratification resulted in 22 (15.8%) cases in the sensitive group, of which 13 received adjuvant chemotherapy and nine were assigned to no treatment; 117 (84.2%) patients were considered nonsensitive, 60 of whom received adjuvant chemotherapy, and 57 of whom received no adjuvant therapy. Among nonsensitive patients, 3-year survival rates were 87.6% with adjuvant chemotherapy and 84.9% with no therapy, indicating no significant difference between groups. Among responders, however, there was a significant difference in 3-year survival rates: 100% for the adjuvant group and 62.5% for the no-treatment group (P = .0351). These findings suggest that histopathologic assessment following preoperative UFT chemotherapy provides information to predict fluoropyrimidine sensitivity. We believe grade 1B patients (19.8%) may respond to modulated fluorouracil. We also recommend the use of other drugs, such as irinotecan (CPT-11 [Camptosar]) and oxaliplatin, for patients with tumor responses of grades 0 and 1A.

Aged↗
PubMed1999

[Comparative study of histopathological effects of preoperative chemotherapy using UFT and in vitro MTT assay of colonoscopy specimens from patients with colorectal cancer].

In previous studies, we demonstrated that the histopathological effects of 5-FU on colorectal cancer corresponded with the clinical effects. We measured the chemosensitivity of colorectal cancer to 5-FU by MTT assay using specimens from colonoscopy, and compared this with the histopathological effects. Forty-five patients with histologically proven colorectal cancer were enlisted for this study. Patients first underwent colonoscopy, and MTT assays were performed. Afterwards, preoperative UFT chemotherapy at a dose of 600 mg/day was given over 10 days before the operation. The histopathological effects of the resected tumors in response to 5-FU were estimated. Seven of 37 patients were judged sensitive to 5-FU by MTT assay. The response rate was 18.9%. On the other hand, 30 of 37 were evaluated as insensitive. Five of 7 patients with sensitivity to 5-FU were also evaluated as sensitive according to the histopathological effects. The sensitivity true positive rate was 71.4%. Twenty-nine patients without sensitivity to 5-FU were also evaluated as insensitive according to the histopathological effects. The specificity true negative rate was 96.7%, and the accuracy rate was 91.9%. The chemosensitivity of colorectal cancer to 5-FU, determined by MTT assay, was nearly consistent with the histopathological effects, so it may also be expected to correspond with the clinical effects.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Seroprevalence and subtype distribution of hepatitis C virus among blood donors and intravenous drug users in northern/northeastern Thailand.

The prevalence of antibodies against hepatitis C virus (HCV) and the distribution pattern of HCV subtypes were analyzed among healthy blood donors and intravenous drug users (IVDUs) in northern/northeastern Thailand. The prevalence of anti-HCV antibodies was 3.2% (26/820) among blood donors in Khon Kaen, while it was 90% (71/79) among IVDUs in Chiang Rai. HCV RNA was detected in all anti-HCV-positive sera collected from blood donors and IVDUs tested, as determined by reverse transcription-PCR analysis. Sequence analyses of amplified fragments of the HCV genome revealed that in Khon Kaen and Chiang Rai, Thailand, HCV-3a (50-60%) was the most common HCV subtype, followed by HCV-1a, HCV-1b, and subtypes of clade 6, each at 10-20%.

Adolescent↗
PubMed1999

[Low-dose CDDP and 5-FU for head and neck cancer patients].

Combination chemotherapy with CDDP and 5-FU is one of the most effective regimens for head and neck cancer. Recent studies have focused on biochemical modulation in the combination of CDDP and 5-FU. We studied the difference in effectiveness and adverse effects between two CDDP administration schedules for CDDP-5-FU combination chemotherapy. For regimen A, CDDP was administered on 5 consecutive days from day 1 to day 5, with a daily dose of 16 mg/m2. For regimen B, CDDP was administered at 80 mg/m2 on day 1. 5-FU was administered at 600 mg/m2/day in a continuous drip infusion for 120 hours from day 1 to day 5 for regimens A and B. Twenty-seven patients with head and neck squamous cell carcinoma were included in this study, and received either regimen A or B. Thirteen patients were given regimen A and 14 regimen B. With regimen A, 3 patients showed CR and the response rate was 76.9%. With regimen B, 3 patients showed CR and the response rate was 64.3%. The rates of efficacy were not different between regimen A and B. In contrast, a difference was seen with organ toxicity. Regimen B was more toxic for renal function than regimen A, while regimen A showed greater toxicity to bone marrow function. Acute nausea and vomiting were observed more frequently with regimen B. The difference in organs and symptoms of adverse effects, according to the schedule of CDDP administration would seem to be important in the treatment of head and neck cancer patients. The schedule of CDDP administration should be adjusted depending on the renal and bone marrow functions of the patients. Because multiple infusion of CDDP proved to be efficacious, low-dose CDDP and 5-FU will have a role for patients with head and neck squamous cell carcinoma. We also introduce other reports on the efficacy of low-dose CDDP and 5-FU.

Antiemetics↗
PubMed1999

[Small cell lung cancer associated with paraneoplastic cerebellar degeneration and Lambert-Eaton myasthenic syndrome].

A 57-year-old man was admitted to our hospital in November 1997 because of dysarthria, progressive ataxia, generalized weakness, and incoordination in both hands. He had been aware of the dysarthria 6 months earlier. Chest roentgenograms and computed tomographic films disclosed a 5 cm x 6 cm mass in the left S3b. The patient was given a diagnosis of small cell lung cancer (T3N2M0, stage IIIA) associated with paraneoplastic cerebellar degeneration (PCD). Three courses of chemotherapy (carboplatin and etoposide) eliminated the tumor and slightly alleviated the PCD symptoms. In March 1998, electromyograms revealed a fall in the single-stimulated M wave and a waxing phenomenon that had not been observed on admission. Anti-P/Q type voltage gated calcium channel antibody was detected in serum samples obtained on admission and after chemotherapy. These findings confirmed an association with Lambert-Eaton myasthenic syndrome. No relapse of the tumor has been observed 15 months after the last course of chemotherapy.

Autoantibodies↗
PubMed1998

DNA topoisomerase inhibitors induce reversible senescence in normal human fibroblasts.

Inhibitors of DNA topoisomerases I and II induced arrest in cell division in normal human fibroblasts depending on cell divisions. Arrested cells showed morphology similar to those of normally senesced cells and strongly induced senescence-associated beta-galactosidase. In these cells, p16ink4a was upregulated, whereas p21waf1 or p53 was not altered. Upon removal of the inhibitors, the cells resumed growth but their cumulative population doublings were reduced dose dependently. Accelerated telomere shortening was not observed in the arrested cells. These results suggest that DNA topoisomerase inhibitors are efficient and reversible inducers of premature senescence in normal human cells.

Cellular Senescence↗
PubMed1998

Overexpression of AML1 renders a T hybridoma resistant to T cell receptor-mediated apoptosis.

The AML1 gene, which encodes the DNA binding subunit of the heterodimeric transcription factor, PEBP2/CBF, is involved in several types of chromosomal translocations associated with human acute myeloid leukemia, and has been shown by gene targeting to be essential for the development of definitive hematopoiesis in the murine fetal liver. In addition, the gene is expressed abundantly in T lymphocytes and has been implicated in T cell specific gene expression. In the present study we examined the function of AML1 in T cell receptor (TCR)-mediated, Fas/Fas-ligand dependent apoptosis of a T hybridoma line, DO11.10. Several independent cell clones overexpressing the AML1 protein were isolated by transfecting AML1 cDNA into these cells. These clones possessed an increased level of PEBP2/CBF DNA binding activity and were found to be resistant to apoptosis induced by anti-CD3 antibody treatment. Northern blot analysis revealed that induction of the Fas-ligand transcript was markedly suppressed in the anti-CD3 treated clones. Instead, expression of IL-2 receptor alpha subunit (IL-2R alpha), which is a manifestation of proliferative TCR signaling, was induced. This was in contrast to the parental, anti-CD3 treated DO11.10 cells where induction of Fas-ligand but not of IL-2R alpha was observed. Resistance of the AML1 overexpressing cell clones to TCR-mediated apoptosis is most likely attributable to the lack of Fas-ligand induction, since simultaneous treatment with anti-CD3 and anti-Fas antibodies caused apoptosis of the clones. The overall results suggest that the AML1 protein may play a pivotal role in switching TCR signaling between apoptosis and cell proliferation in T lymphocytes.

Animals↗
PubMed1998

Prolyl endopeptidase from Sphingomonas capsulata: isolation and characterization of the enzyme and nucleotide sequence of the gene.

Prolyl endopeptidase (prolyl oligopeptidase, EC 3.4.21.26) was purified from Sphingomonas capsulata IFO 12533, and its gene was cloned and expressed in Escherichia coli. The recombinant enzyme was markedly inhibited by diisopropyl phosphofluoridate and hardly affected by SH reagents or metal chelators, similar to the native enzyme purified from S. capsulata. Nucleotide sequencing analysis revealed an open reading frame of 2169 bp, coding for a protein of 723 amino acids with a predicted molecular weight of 78,433. The amino acid sequence was 39.6, 45.3, 38.9, and 38.3% homologous to Flavobacterium meningosepticum, Aeromonas hydrophila, porcine brain, and human T cell prolyl endopeptidase, respectively. A region near the C-terminus and the region containing the putative catalytic triad residues were highly conserved. The enzyme was crystallized by the hanging drop vapor diffusion method, using ammonium sulfate as a precipitant.

Amino Acid Sequence↗
PubMed1998

Expression of membrane-bound transferrin-like protein p97 on the cell surface of chondrocytes.

A concanavalin-A-binding protein of 76 kDa was purified from the plasma membrane fraction of rabbit chondrocyte cultures. Amino acid sequencing of the N-terminal region and of tryptic peptides of the protein, in addition to sequencing of its cDNA revealed that this protein is highly similar to the tumour-associated antigen p97. Hence, it was concluded that this protein is the rabbit form of p97. Western blotting, Northern blotting and reverse-transcription PCR analyses indicated that rabbit p97 is expressed at high levels in cartilage and chondrocytes, but is barely detectable in the bone, liver, kidney, small intestine, eye, pancreas, heart, testis, skeletal muscle, spleen and fibroblasts. Immunocytochemical and immunohistochemical analyses demonstrated that p97 is expressed in the plasma membrane of chondrocytes. p97 transcript was detected in all zones of the cartilage but the level was relatively low in the hypertrophic zone. These findings suggest that p97 is involved in maintaining the cell surface characteristics of chondrocytes.

Amino Acid Sequence↗
PubMed1998

Clustering of human chromosome fragments on the mouse genome by chromosome-mediated gene transfer.

Pieces of metaphase chromosomes prepared from mouse cells containing neo-tagged human chromosome 7 were transferred to mouse cells with calcium phosphate to isolate G418-resistant clones. FISH analysis revealed that the majority of them contained human DNA at a single site on their genome. These transformants contained STS markers mapped to various regions of chromosome 7. It is thus suggested that pieces of human chromosomes tend to assemble and integrate on the mouse genome.

Animals↗
PubMed1998

A mutation in succinate dehydrogenase cytochrome b causes oxidative stress and ageing in nematodes.

Much attention has focused on the aetiology of oxidative damage in cellular and organismal ageing. Especially toxic are the reactive oxygen byproducts of respiration and other biological processes. A mev-1(kn1) mutant of Caenorhabditis elegans has been found to be hypersensitive to raised oxygen concentrations. Unlike the wild type, its lifespan decreases dramatically as oxygen concentrations are increased from 1 to 60%. Strains bearing this mutation accumulate markers of ageing (such as fluorescent materials and protein carbonyls) faster than the wild type. We show here that mev-1 encodes a subunit of the enzyme succinate dehydrogenase cytochrome b, which is a component of complex II of the mitochondrial electron transport chain. We found that the ability of complex II to catalyse electron transport from succinate to ubiquinone is compromised in mev-1 animals. This may cause an indirect increase in superoxide levels, which in turn leads to oxygen hypersensitivity and premature ageing. Our results indicate that mev-1 governs the rate of ageing by modulating the cellular response to oxidative stress.

Aging↗
PubMed1998

The chimeric protein, PEBP2 beta/CBF beta-SMMHC, disorganizes cytoplasmic stress fibers and inhibits transcriptional activation.

The chromosomal inversion 16(p13;q22) associated with human acute myeloid leukemia generates the chimeric PEBP2 beta/CBF beta-SMMHC gene. The PEBP2 beta/CBF beta portion of the chimeric polypeptide harbors most of the amino acid sequence of the PEBP2 beta/CBF beta protein, the non-DNA binding subunit of the heterodimeric transcription factor, PEBP2/CBF, whereas the SMMHC portion of the chimera consists of the rod domain of the smooth muscle myosin heavy chain molecule. In this study we examined the subcellular localization of the chimeric protein and its effect both on stress fibers and transcriptional activation by transfecting cDNA into tissue culture cells. The localization of the chimera was investigated by immunocytochemical staining of cells and was found to be both cytoplasmic and nuclear. One aspect of the effect of expression of the chimera was a drastic alteration of cell morphology. The cells appeared elongated and possessed long cytoplasmic processes. Double fluorescent labeling revealed disorganization of the stress fibers and an altered F-actin staining pattern in the transfected cells. Studies using a deletion mutant showed that both the PEBP2 beta/CBF beta and SMMHC domains are necessary for the induction of the morphological alteration. A significant proportion of the chimeric protein was retained in the cytoskeleton after detergent extraction of the cells and could be recuperated as a membrane fraction, suggesting that this is one of the probable sites of action of the PEBP2 beta/CBF beta-SMMHC protein. Another effect of the chimeric protein was inhibition of transcriptional activation dependent on the PEBP2/CBF binding DNA sequence. However, deregulation of PEBP2/CBF site dependent transcription by itself was not sufficient to induce cell morphological changes. Taken together, these results indicate that the PEBP2 beta/CBF beta-SMMHC chimeric protein acts at two levels, at the level of stress fiber organization and at the level of transcriptional activation. We suggest that the action of PEBP2 beta/CBF beta-SMMHC depends to a great extent on whether it is located in the cytoplasm or in the nucleus.

Acute Disease↗
PubMed1998

Chronological Changes of Microcalcifications of Breast Carcinoma.

BACKGROUND: Clustered microcalcifications are important for the detection of breast carcinomas, but few reports have described chronological changes of the microcalcifications. METHODS: The mammographic features of 18 breast cancer cases for which previous survey films were available and in which clustered microcalcifications with no tumor shadows were recognized at diagnosis were studied. Chronological changeswere analyzed by measuring the increase in the length of areas containing calcifications and the diameters of microcalcifications on mammograms using computerized image analysis. RESULTS: Chronological changes in the length of areas of microcalcifications were classified into two types by simple linear regression. Fast increase was common in the comedo type of carcinoma and slow increase was common in the non-comedo type. Three of nine cases that received follow-up examinations on two or more occasions eventually changed from slow type to fast type, and the distributionpattern of diameters of microcalcifications also changed from non-comedo type to comedo type. A follow-up study of 48 cases with a cluster of fewer than five extremely fine calcifications revealed breast carcinoma in 7 patients within 5 years. CONCLUSION: The increase of microcalcifications was generally fast in comedotype and slow in non-comedo type lesions. An increase in the extent of microcalcification was seen occasionally during the last period between follow-up examinations in mixed type tumors, indicating a conversion of the intraductal component to a more malignant grade.

Journal Article↗
PubMed1998

Release of telomeric DNA from chromosomes in immortal human cells lacking telomerase activity.

Some immortal human cell lines lack telomerase activity. These cell lines were found to contain small dispersed DNA hybridizing to TTAGGG repeats. Such DNA was located in their cytoplasm and nuclei. Normal human fibroblasts or telomerase-positive cell lines did not contain such DNA. Upon cloning and sequencing, it was shown to consist of TTAGGG repeats. When electrophoresed on neutral and alkaline agarose gels, it behaved as double-stranded and linear DNA. These results suggest that telomeric DNA is released from chromosomes in association with maintenance of telomeres in telomerase-negative cell lines.

Cell Line↗