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Biomedical subjects

M Fukumoto

Publications and source records attributed to M Fukumoto.

At least 127 records · Page 7Linked to original sources
PubMed1995

Frequent expression of P-glycoprotein/MDR1 by nasal T-cell lymphoma cells.

BACKGROUND: Lethal midline granuloma is now considered to be a malignant lymphoma derived from peripheral T cells or from natural killer cells. The therapeutic outcome of nasal T-cell lymphoma (NL) treated by conventional chemotherapy for non-Hodgkin's lymphoma is poor, although some patients have a good response to radiotherapy. To clarify the mechanisms of drug resistance, the expression of P-glycoprotein (P-gp)/MDR1, which is the product of the multidrug resistance (MDR) 1 gene, and MDR3 mRNA in NL cells, were examined. METHODS: Ten Japanese patients with NL were studied. Nine of these patients were examined before therapy. P-glycoprotein expression and phenotypes of lymphoma cells were examined by immunohistochemical staining using UIC2 as an anti-P-gp monoclonal antibody. In one case, the Rhodamine-123 efflux test was performed. MDR1 and MDR3 mRNA were detected by reverse transcription polymerase chain reaction. RESULTS: Nine of the 10 patients were P-gp positive. In one of nine, functional P-gp expression was observed. MDR1 mRNA was detected in all seven examined patients with P-gp positive NLs, whereas MDR3 mRNA was negative. Retrospectively, patients who received chemotherapy alone had poorer outcome than those treated by combination chemotherapy after irradiation. CONCLUSION: The poor prognosis for patients with NL treated with chemotherapy may be explained by P-gp expression of the NL cells.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed1995

Reduced expression of kan-1 (encoding putative bile acid-CoA-amino acid N-acyltransferase) mRNA in livers of rats after partial hepatectomy and during sepsis.

We isolated a cDNA clone, kan-1, from a rat liver cDNA library using a reverse transcriptase PCR cloning method. The kan-1 cDNA encoded a polypeptide of 420 amino acids, and was 70 and 69% identical in nucleotide and amino acid sequences respectively with human liver bile acid-CoA-amino acid N-acyltransferase (BAT). Thus Kan-1 is probably a rat homologue of human BAT (rBAT). Kan-1/rBAT mRNA was mainly expressed in the livers of adult rats and rats immediately after, but not before, birth. It was expressed in the hepatocytes, the sinusoidal endothelial cells and the Kupffer cells of the liver. An anti-Kan-1/rBAT polyclonal antibody detected a protein of molecular mass 46 kDa in the liver. After partial hepatectomy, the levels of Kan-1/rBAT mRNA decreased at 6 and 12 h in the regenerating liver. In a sepsis model, hepatic expression of Kan-1/rBAT mRNA decreased at 6 and 12 h after caecal ligation and puncture. The kinetics of Kan-1/rBAT mRNA expression suggests that it may play a role in acute-phase reactions.

Acyltransferases↗
PubMed1995

Altered expression of nm23-H1 and c-erbB-2 proteins have prognostic significance in adenocarcinoma but not in squamous cell carcinoma of the uterine cervix.

BACKGROUND: The reduced expression of nm23-H1 protein and/or overexpression of c-erbB-2 protein reportedly is associated with a high incidence of lymphatic metastasis or poor prognosis of the patient in a variety of human malignant tumors. METHODS: The expression patterns of nm23-H1 and c-erbB-2 proteins were analyzed by immunohistochemical staining using formalin fixed, paraffin embedded sections of 88 cases of invasive carcinoma (39 matched pairs of adenocarcinoma and squamous cell carcinoma, 8 cases of adenosquamous carcinoma, and 2 cases of undifferentiated carcinoma) and 31 cases of preinvasive lesions of the uterine cervix. RESULTS: Expression of nm23-H1 was detected in 46% of adenocarcinoma and in 36% of squamous cell carcinoma of the uterine cervix, whereas c-erbB-2 expression was evident in 49% and 38%, respectively. Negative expression of nm23-H1, positive expression of c-erbB-2, and a combined nm23-H1-negative and c-erbB-2-positive expression were associated with a high incidence of lymph node involvement (P = 0.36, P = 0.0015, P = 0.0055, respectively) and with poor prognosis of patients (P = 0.034, P = 0.014, P = 0.00008, respectively) with adenocarcinoma of the uterine cervix, but not in those with squamous cell carcinoma. Multivariate analysis using the Cox's proportional hazard model also revealed that these three factors significantly contributed to the prognosis of patients with cervical adenocarcinoma. CONCLUSIONS: Reduced expression of the nm23-H1 protein, increased expression of the c-erbB-2 protein, and a combined nm23-H1-negative and c-erbB-2-positive expression have prognostic significance in patients with adenocarcinoma, whereas they may not be associated with the prognosis of squamous cell carcinoma of the uterine cervix, nm23-H1 and c-erbB-2 proteins may have different functions according to the subtype of cervical carcinoma.

Adenocarcinoma↗
PubMed1995

A newly established megakaryoblastic/erythroid cell line that differentiates to red cells in the presence of erythropoietin and produces platelet-like particles.

In August, 1992, we established a leukemic cell line (NS-Meg) from a patient in megakaryoblastic transformation of Philadelphia chromosome-positive chronic myeloid leukemia. The NS-Meg cells were positive for alpha-naphthyl acetate esterase and periodic acid-Schiff (PAS) staining and for surface CD4, CD7, CD13, CD34, CD41a, and glycophorin A antigens. Ultrastructurally, the cells had alpha-granules, demarcation membranes, and platelet peroxidase activity. The NS-Meg cells spontaneously produced platelet-like particles which contained alpha-granules, mitochondria and dense bodies, strongly suggesting platelet production. Erythropoietin (Epo), granulocyte/macrophage colony stimulating factor(GM-CSF), and interleukin 3 (IL-3) promoted the growth of NS-Meg cells. Phorbol-12-myristate-13-acetate increased the expression of both CD41a and CD61 antigens. Ten-day exposure to Epo induced mature erythroblasts and red cells. These benzidine-positive cells were positive for hemoglobin F staining. Untreated NS-Meg cells expressed mRNA for the Epo receptor (EpoR), for GATA-1, and for alpha 1, alpha 2 and gamma globin genes. These results indicate that NS-Meg cells undergo terminal differentiation of both megakaryocytic and erythroid lineages. This cell line should be a very useful tool for the investigation of both megakaryocytic and erythroid maturation.

Adult↗
PubMed1995

Can barium enema indicate when colonoscopy will be difficult?

The barium enemas of 48 consecutive patients, who were technically difficult to intubate at colonoscopy, were compared to those of 46 patients who were not. Measurements were taken of colonic length and mobility, and an assessment made of diverticular disease. Rectosigmoid length (mean difficult group = 61 cm, mean control = 54 cm, P = 0.01) and total colonic length (mean difficult group = 157 cm, mean control = 140 cm, P < 0.0001) were greater in the difficult colonoscopy group as were transverse colon mobility (mean difficult group = 10 cm, mean control = 7 cm, P = 0.003) or redundancy (transverse colon reaching the true pelvis on the erect film); 65% difficult group vs 17% control group, P < 0.0001. The presence of moderate or severe diverticular disease was also greater in the difficult (23%) compared to the control (4%) group, P = 0.02. When available, assessment of a previous barium enema is a useful guide to probable technical difficulty of colonscopy. It may allow appropriate allocation of potentially difficult cases to specialist endoscopy lists.

Adolescent↗
PubMed1995

Mutation of the nm23 gene, loss of heterozygosity at the nm23 locus and K-ras mutation in ovarian carcinoma: correlation with tumour progression and nm23 gene expression.

Alteration of expression levels of the nm23 genes has previously been correlated with metastatic status of ovarian epithelial carcinoma. To elucidate the relevance of the qualitative changes of the nm23 genes to progression of ovarian carcinoma and/or to nm23 expression levels of the tumour, 41 samples of epithelial ovarian tumours [three benign, three low malignant potential (LMP), and 35 frankly malignant tumours] were studied for mutation of the nm23-H1 and the nm23-H2 genes using single-strand conformational polymorphism (SSCP) analysis. In addition, loss of heterozygosity (LOH) at the nm23 locus on chromosome 17q was studied by CA repeat polymorphism analysis. Mutation of the K-ras gene was also analysed in the same specimens. A novel mutation of the nm23 gene was found in one case of stage III serous carcinoma without lymph model metastases. Sequencing of the subcloned mutant cDNA revealed a missense mutation from TGG to CGG at codon 133 of the nm23-H2 gene, resulting in a change from Trp to Arg. LOH at the nm23 locus was detected in 5 of 23 (21.7%) informative cases of ovarian carcinoma. Mutation of the K-ras gene was detected in 2 of 35 (5.7%) carcinomas at codons 12 and 13 respectively. There was no correlation between clinical stage or metastatic status of ovarian carcinoma and nm23 mutation, LOH at the nm23 locus or K-ras mutation. The expression levels of both the nm23-H1 and the nm23-H2 genes were lower in the tumour with nm23-H2 mutation and higher in those with K-ras mutation. This suggests that mutation of the nm23 genes and the K-ras gene affects carcinogenesis or progression of ovarian carcinoma by modulating expression of the nm23 genes.

Adult↗
PubMed1995

Induction of CL100 protein tyrosine phosphatase following transient forebrain ischemia in the rat brain.

Protein tyrosine phosphorylation is thought to play an important role in the regulation of neural function. To elucidate the role that protein tyrosine phosphatases (PTPs) may play in the postischemic brain, PTPs expressed in regions of the rat brain vulnerable to transient forebrain ischemia were examined. With the reverse-transcriptase polymerase chain reaction using degenerate primers, three PTPs, STEP, PTP delta, and SH-PTP2, were identified. They were expressed in the hippocampus 12 h after transient ischemia for 20 min. During the reperfusion period, the mRNA levels of these PTPs were not different from those in sham-operated rats. In contrast, a fourfold increase in the mRNA level of CL100 (3CH134), a PTP that is inducible by oxidative stress, was detected by Northern blotting in the hippocampus and cerebral cortex 1 h after the onset of reperfusion. In situ hybridization histochemistry showed a slight increase in the level of CL100 mRNA in neuronal cells in the hippocampus and cortex of postischemic rats compared to control rats. These findings suggest that PTPs play a role in the normal function of the hippocampus and cerebral cortex and demonstrate that ischemia induced CL100 expression.

Amino Acid Sequence↗
PubMed1995

Acute childhood diarrhoea and maternal time allocation in the northern central Sierra of Peru.

Interventions to improve child health depend, at least implicitly, on changing maternal knowledge and behaviour and a reallocation of maternal time. There have been few studies, however, of the time cost involved in the adoption of new health technologies and even fewer that examine changes in maternal activities in response to child illness. The present study examines maternal daytime activities and investigates changes that occur when children are ill. We examine the impact of acute childhood diarrhoea episodes on the activity patterns of the mother/caretaker in this setting. The results show that mothers alter their usual activity patterns only slightly in response to acute diarrhoea episodes in their children. They continue to perform the same variety of activities as when the children are healthy, although they are more likely to perform them with the child 'carried' on their back. There is some indication that diarrhoea perceived to be more severe did result in the mother acting as caretaker more frequently. These findings have important implications for health interventions that depend on changing the amount of maternal or caretaker time spent for child health technologies, but the implications may vary depending on the reasons for the observed lack of changes in caretaker activities.

Child Care↗
PubMed1995

Expression of vav proto-oncogene by nonhematopoietic trophoblast cells at the human uteroplacental interface.

Vav is a signal transducing molecule containing SH2 and SH3 domains and a guanine nucleotide releasing factor-like domain. Its expression is thought to be highly specific for hematopoietic cells. Here we describe the expression of vav transcripts in human nonhematopoietic trophoblasts. By northern blotting, expression of 2.8-kb vav mRNA was detected in human decidual, placental, and chorionic villous tissues and in a choriocarcinoma cell line BeWo. By in situ hybridization, vav mRNA was found to be expressed in the cytotrophoblast shell and columns and in the extravillous trophoblasts in the maternal decidua from the first through third trimesters. Vav mRNA was also detected in villous syncytiotrophoblasts during the second and third, but not the first, trimesters. When 1 microM oligodeoxynucleotide antisense to the vav mRNA was added to the medium, growth of BeWo cells was significantly inhibited. These results suggest that vav plays an important role for successful implantation and placental development by regulating development of trophoblasts.

Amino Acid Sequence↗
PubMed1995

Enhanced susceptibility of c-myc antisense oligonucleotide-treated human renal cell carcinoma cells to lysis by peripheral blood lymphocytes.

C-myc oncogene expression has been implicated in the poor prognosis of human renal cell carcinoma (RCC), and these tumor cells are resistant to cytotoxic effector cells. We hypothesized that the resistance of RCC cells to lysis by cytotoxic effector lymphocytes might be regulated by c-myc expression. The present study tested this hypothesis by examining the effect of c-myc antisense oligonucleotide treatment on the susceptibility of RCC to lysis by cytotoxic lymphocytes. The Caki-1 human RCC cell line constitutively expresses c-myc mRNA, and treatment with c-myc antisense oligonucleotide resulted in a significant inhibition of the expression of c-myc mRNA and enhanced susceptibility to lysis by peripheral blood lymphocytes (PBL). The enhanced susceptibility to lysis was observed by PBL derived from both normal donors and patients with RCC. The susceptibility of c-myc antisense oligonucleotide-treated Caki-1 cells to lysis by lymphokine-activated killer (LAK) cells, natural killer (NK) cells, and tumor-infiltrating lymphocytes (TIL) was also enhanced. Furthermore, enhanced susceptibility was also seen when freshly isolated autologous tumor cells were used as target cells. The mechanism of the enhanced susceptibility of c-myc antisense oligonucleotide-treated Caki-1 cells to lysis was examined. No effect was observed on the expression of major histocompatibility complex (MHC) class I and MHC class II on the tumor cells. However, there was a modest increase in the frequency of effector-target binding. Further, c-myc antisense oligonucleotide-treated Caki-1 cells were more susceptible to lysis by tumor necrosis factor-alpha (TNF-alpha). The findings of this study demonstrate that c-myc antisense oligonucleotide directly affects established RCC cells and freshly isolated RCC cells by rendering them more susceptible to lysis by PBL, LAK cells, NK cells, and T lymphocytes. The enhanced susceptibility may be due in part to the enhanced sensitivity to TNF-alpha and to the augmentation of PBL binding to tumor cells. The possible clinical implications of these findings are discussed.

Adolescent↗
PubMed1995

Multidrug resistance-associated protein-mediated multidrug resistance modulated by cyclosporin A in a human bladder cancer cell line.

A doxorubicin-resistant subline (5637/DR5.5) from human bladder cancer cells (5637) was induced by stepwise increase in the doxorubicin concentration. 5637/DR5.5 cells were cross-resistant to vinblastine and etoposide but not to mitomycin C and cisplatin. We analyzed the mdr1, MRP (multidrug resistance-associated protein), and DNA topoisomerase II gene expression using the reverse transcription polymerase chain reaction assay (RT-PCR) and investigated possible differences in the accumulation and efflux of radiolabeled daunorubicin. 5637/DR5.5 cells do not express the mdr1 gene, but the expression levels of MRP are markedly higher than in drug-sensitive 5637 cells. The intracellular accumulation of radiolabeled daunorubicin was markedly decreased in the 5637/DR5.5 cells in comparison with the parent cells. This reduced drug accumulation was associated with an enhanced drug efflux, but was reversed when cells were incubated with cyclosporin A. Cyclosporin A at the concentration of 5 microM caused 3.4-fold enhancement of daunorubicin-sensitivity in the 5637/DR5.5 cells. On the other hand, there was no difference in DNA-topoisomerase II activity between the parent and resistant cells. The resistance of the 5637/DR5.5 cells is therefore associated with an enhanced drug efflux mediated by the MRP gene overexpression, as distinct from P-glycoprotein, and is modulated by cyclosporin A.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Low incidence of point mutations in H-, K- and N-ras oncogenes and p53 tumor suppressor gene in renal cell carcinoma and peritoneal mesothelioma of Wistar rats induced by ferric nitrilotriacetate.

An iron chelate, ferric nitrilotriacetate (Fe-NTA, induces renal proximal tubular damage, a consequence of iron-catalyzed free radical reactions, that finally leads to a high incidence of renal cell carcinoma (RCC) in rodents. Previous studies have identified, within 24 h after administration of Fe-NTA, lipid peroxidation products, aldehyde-modified proteins and a variety of modified DNA bases such as 8-hydroxyguanine that may be mutagenic in vivo. In the present study, pathological features of the RCCs were studied, and, in an effort to correlate them with carcinogen-specific molecular events in Fe-NTA-induced carcinogenesis, the H-, K- and N-ras oncogenes and the p53 tumor suppressor gene were investigated for the presence of mutations. Fe-NTA-induced RCCs showed similarity to human RCCs in that they are often invasive, metastatic and fatal. None (0 of 12) of the tumors had mutation in codons 12, 13 and 61 of the H-, K- and N-ras genes by direct sequencing. Only one (1 of 12) tumor with high grade histology revealed a CGC-to-CTC (Arg to Leu) transversion in codon 246 of the p53 gene by the use of single strand conformation polymorphism (SSCP) analysis and direct sequencing. High expression of mutant p53 protein was confirmed by Western blotting and immunohistochemistry. Study of three peritoneal mesotheliomas induced by Fe-NTA revealed no mutation in ras and p53 genes. These results suggest that the ras and p53 genes are not the major targets of mutation in Fe-NTA-induced carcinogenesis of kidney and mesothelium. Instead, p53 mutation may work for potentiation of malignant character in Fe-NTA-induced renal carcinogenesis.

Animals↗
PubMed1995

A sporadic case of Ehlers-Danlos syndrome type IV: diagnosed by a morphometric study of collagen content.

A sporadic case of a young woman with Ehlers-Danlos syndrome (EDS) type IV is described. Multiple aneurysms of medium-sized arteries were noted. Histological study revealed deposition of acid mucopolysaccharides in the media of major arteries and in the intima of smaller arteries with intimal thickening. Systemic changes related to stenosis were observed in arteries more than 100 microns in diameter. Histologic study revealed hyperplasia of adipocytes in the submucosal layer of the intestines and the trachea, and fibrosis of Langerhans' islets of the pancreas. Typical signs for EDS such as skin hyperelasticity and joint hypermobility, and positive family history were not present. However, type III collagen was not detected on frozen sections from either the skin or the anterior cerebral artery by immunohistochemical quantification. Thus, it was concluded that the present case is a variant of EDS.

Adolescent↗
PubMed1995

The quest for a more acceptable bowel preparation: comparison of a polyethylene glycol/electrolyte solution and a mannitol/Picolax mixture for colonoscopy.

Eighty-nine consecutive patients attending for day-case colonoscopy were randomly allocated either polyethylene glycol/balanced electrolyte (PEG) mixture (n = 45) or a mannitol/Picolax mixture (n = 44). Both preparations were administered in two fractions. Patients recorded their experience of the preparation on a questionnaire and one of two experienced endoscopists (unaware of the type of preparation given) assessed the result of bowel cleansing. Carbon dioxide insufflation was used for all examinations. Good/excellent bowel cleansing occurred in significantly more patients given PEG, 43 (96%), than those allocated mannitol/Picolax, 34 (77%), p = 0.01. More patients receiving mannitol/Picolax were able to complete the preparation in full than patients receiving PEG (38 vs 27, p = 0.01). More patients found the taste of mannitol/Picolax pleasant compared to PEG (46% vs 20%). Both preparations had a similar side-effect profile. Of those patients tested, 13% receiving mannitol/Picolax had a postural drop in blood pressure and blood parameters suggestive of mild dehydration. A fractionated administration of PEG as a bowel preparation for day-case colonoscopy is well tolerated and superior as a cleansing agent to a mannitol/Picolax combination. Provided carbon dioxide is used as the insufflating agent, mannitol/Picolax is an acceptable alternative in fit, young patients intolerant of PEG.

Administration, Oral↗
PubMed1995

Long term complete remission in primary plasma cell leukemia.

A 76-year-old female was diagnosed as having primary plasma cell leukemia (PCL), based on abundant atypical plasma cells in the circulation and bone marrow, monoclonal kappa light chain in the serum and urine, the immunophenotype of the plasma cells and the lack of preceding multiple myeloma. The patient was treated with melphalan and prednisolone (MP), and complete remission (CR) was achieved; this was maintained for 28 months. The duration of CR in this patient appears to be the longest of those reported in well-documented primary PCL patients who have been treated with MP chemotherapy.

Aged↗
PubMed1995

A study of cysts in the oral region. Cysts of the jaw.

Clinical cases of cysts of the jaw treated in the Department of Oral Surgery of our university during the 10 y between 1980 and 1989 were studied clinically. Patients with radicular cyst, dentigerous cyst, odontogenic keratocyst and postoperative maxillary cyst, which were found at relatively high frequencies, were further analyzed with regard to age, sex and anatomical distribution. A diagnosis of cyst was established in 1,444 patients during the above period, and 1,234 (85.5%) of them had cysts of the jaw. According to a pathological classification by Ishikawa's method, these patients included 509 (41.2%) with radicular cyst, 259 (27.0%) with dentigerous cyst, 95 (7.7%) with odontogenic keratocyst and 267 (21.6%) with postoperative maxillary cyst. The pattern of age distribution in cases of radicular cyst, odontogenic keratocyst and postoperative maxillary cyst was similar to that found in previous studies. Among patients with dentigerous cyst, those aged under 20 y accounted for about 60%. Radicular cyst occurred most frequently in the maxillary lateral incisors, dentigerous cyst in the mandibular wisdom teeth, and odontogenic keratocyst in the region between the mandibular molar and the ramus of the mandible.

Adolescent↗
PubMed1995

Dual-isotope SPECT of skull-base invasion of head and neck tumors.

UNLABELLED: Skull-base invasions of head and neck tumors were examined by simultaneous bone and tumor dual-isotope SPECT (S-SPECT) with 99mTc-hydroxy-methylene-diphosphonate (99mTc-HMDP) and 201Tl-chloride. The effectiveness and reliability of tumor diagnosis by this method was the primary interest in this study. METHODS: Before S-SPECT imaging, a phantom experiment using dried skull-bone specimens was performed to establish anatomical details of the skull base with the SPECT camera. Radionuclide crosstalk, window widths and control patients were also examined prior to S-SPECT imaging. Twenty patients with suspected tumor invasion of the skull base underwent S-SPECT. RESULTS: Preliminary experiments revealed that crosstalk effects could be disregarded with adequate window width and routine administrative doses of the radionuclides. S-SPECT detected bone destruction and the extent of tumor invasion for all 12 patients in whom skull-base involvement was diagnosed by CT or MRI. For the three patients in whom CT or MRI revealed no tumor invasion, the S-SPECT images did not show any abnormal accumulation in similar regions. In the remaining five patients without CT and MRI confirmation of skull-base invasion, the S-SPECT findings showed skull-base abnormalities in three. Tumor invasion was confirmed surgically or by clinical follow-up. The remaining two patients had negative S-SPECT images. CONCLUSION: S-SPECT is an effective and reliable diagnostic technique for detecting tumor invasion in the complex bony regions of the skull base.

Adult↗