Biomedical subjects

Y Maeda

Publications and source records attributed to Y Maeda.

At least 235 records · Page 13Linked to original sources

PubMed2000

[Significance of reduction surgery for giant hepatocellular carcinoma with diffuse lung metastases and multiple intrahepatic metastases].

Continuous systemic infusion of low-dose cisplatin (CDDP) (10 mg/body/day) and 5-fluorouracil (5-FU) (500 mg/body/day) was performed for advanced hepatocellular carcinoma (HCC) after hepatectomy with diffuse lung metastases and multiple intrahepatic metastases. This infusion chemotherapy, cisplatin was continued for five days, and discontinued for two days, whereas 5-fluorouracil was administered every day and repeated four weeks as one course basally. Remnant metastases had almost disappeared after systemic chemotherapy for 10 weeks. In our experience, the response rate in 13 patients who underwent reduction surgery for multiple HCC was 84.6%. Continuous infusion of low-dose CDDP/5-FU may be effective in patients having absolute non-curative resection.

Adult↗

PubMed2000

[Hepatocellular carcinoma with tumor thrombus in the portal and hepatic veins treated successfully with hepatectomy and chemotherapy--a case report].

A 39-year-old woman was admitted to our hospital because of advanced hepatocellular carcinoma. She had good liver function with clinical Stage I. Abdominal ultrasonographic study and CT scan revealed a huge tumor of 12 cm in diameter in the left lobe of the liver, with tumor thrombi in the portal and hepatic veins. A chest CT scan demonstrated multiple bilateral lung metastases from 5 to 10 mm in size. An extended left hemihepatectomy with extirpation of the portal and hepatic venous tumor thrombi was performed. On postoperative day 7, low-dose cisplatin (10 mg/day-5 days/week) and 5-fluorouracil (250 mg/day-continuous for 7 days/week) were administered intravenously. Four weeks after chemotherapy, CT scan revealed no recurrence in the liver and no change in the lung metastases. The patient is now being treated on an outpatient basis with no change in the metastatic tumors.

Adult↗

PubMed2000

[Progress in chemotherapy for colorectal cancer].

Among colorectal cancer patients with recurrent or metastatic sites, survival was significantly prolonged for a group undergoing LV/5-FU therapy based on biochemical modulation compared with a group receiving no chemotherapy (best supportive care). LV/5-FU combination therapy is recognized as the standard therapy for colorectal cancer, but recently LV/5-FU plus oxaliplatin and LV/5-FU plus CPT-11 have appeared to be more effective than LV/5-FU in some randomized studies. Capecitabine, UFT/LV and S-1 are new oral drugs that are at least comparable to LV/5-FU in antitumor activity, but superior in tolerability, which benefits the patients' quality of life, especially elderly patients with colorectal cancer. Clinical combination studies using CDDP or CPT-11 with these oral drugs are now being performed. Much is expected of these drugs.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2000

Allogeneic peripheral blood stem cell transplantation in 23 adult patients with hematologic malignancies: a single-center experience.

We describe a single-center experience of 23 consecutive patients (median age, 35 years) with hematologic malignancies who received allogeneic peripheral blood stem cell transplants (alloPBSCTs) from HLA-identical siblings. Ten patients had standard-risk disease and 13 had high-risk disease. Twenty-one patients received alloPBSCT as a primary transplant, and the remaining 2, with high-risk disease, as a second transplant after posttransplantation relapse. All donors received daily subcutaneous injections of granulocyte colony-stimulating factor at a dose of 10 microg/kg, and peripheral blood stem cells were collected by 1 to 3 aphereses. Median numbers of CD34+ and CD3+ cells infused were 5.8 x 10(6)/kg (range, 1.3-19.7 x 10(6)/kg) and 4.9 x 10(8)/kg (range, 1.9-8.6 x 10(8)/kg), respectively. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin A (CyA) and methotrexate (18 patients) or CyA and methylprednisolone (5 patients). Rapid hematologic engraftment was observed in 20 of the 23 patients. Median days to absolute neutrophil counts >0.5 x 10(9)/L and platelet counts >20 x 10(9)/L were 12 (range, 9-18 days) and 14 (range, 10-128 days), respectively. Acute GVHD of grade 2-4 was observed in 6 of 20 evaluable patients (30%) and extensive chronic GVHD in 8 of 15 evaluable patients (53%). Ten of the 23 patients (44%) were surviving in continuous complete remission 191 to 1492 days (median, 643 days) posttransplantation. Treatment-related death within 100 days posttransplantation was observed in 6 of the 23 patients (26%). Six of the 23 patients (26%) developed relapse at a median 81 days (range, 38-160 days) posttransplantation. Further study is needed to assess the precise benefits of alloPB-SCT compared with allogeneic bone marrow transplantation.

Adolescent↗

PubMed2000

[Change in skin reactivity to common allergens in allergic patients over a 30-year period. Association with aeroallergen load].

Five-year changes in the percentage of positive intradermal test to allergens in patients with bronchial asthma (BA) and allergic rhinitis (AR) over a period of 30 years from 1969 to 1998 were analyzed, with consideration of their association with the yearly changes in the levels of airborne pollens and molds over 30 years. Allergens used throughout the period were house dust, pollens from various plants (Japanese cedar, pine, oak, Japanese alder, Zelkova, orchard grass, ragweed, mugwort and Japanese hop) and molds (Alternaria, Cladosporium, Aspergillus, Penicillium and Candida). Overall percentages to house dust were higher in BA patients than in AR patients, but those to pollens were distinctly higher in the latter. Those to molds were higher in BA patients, except that those to Alternaria were about the same in both BA and AR patients. Therefore, the clinical expression of allergy may differ according to the type of allergen to which subjects are sensitized. Over the course of 30 years, the increase in the percentage of positive intradermal test to all of the allergens used was noted in both BA and AR patients, although this did not always reflect the aeroallergen load. This includes the two extremes to pollens from Japanese cedar and pine, either of which is the most common source of allergen in Japan. Significant increases in the percentages to Japanese cedar pollen (from 12.5% to 54.4% in BA patients, and from 35.1% to 81.5% in AR patients) appeared to be roughly correlated to marked increases in pollen count. In contrast, that to pine pollen was kept low at about 2%, because of their weak allergenicity, but abruptly increased to 5-6% in the last decade, despite the almost invariable pollen count over the last 30 years. Therefore, the increased sensitivity to aeroallergens may also be associated with other factors besides their load in the air.

Adult↗

PubMed2000

Successful engraftment of allogeneic peripheral blood stem cell transplant after nonmyeloablative preparative regimen with cytarabine and cyclophosphamide: report of 2 cases.

We report our experience with allogeneic peripheral blood stem cell transplantation (allo-PBSCT) following a nonmyeloablative conditioning regimen consisting of cytarabine (8 g/m2) and cyclophosphamide (120 mg/kg) in the treatment of 2 patients aged 50 and 55 years with refractory chronic myelomonocytic leukemia and chronic myeloid leukemia in accelerated phase, respectively. Our nonmyeloablative regimen was well tolerated by older patients at high risk of regimen-related toxicity by the conventional conditioning regimen but was immunosuppressive enough to achieve mixed chimerism. After allo-PBSCT, we monitored chimerism in these patients by fluorescence in situ hybridization using X- and Y-specific probes and polymerase chain reaction-based analysis of a variable number of tandem repeats. We found that full chimerism and graft-versus-leukemia (GVL) effects could be induced in these patients by donor lymphocyte infusions and withdrawal of posttransplantation immunosuppressive therapy. Our observations suggest that a nonmyeloablative conditioning regimen can establish mixed chimerism and that donor lymphocyte infusion may induce GVL effects in older patients at high risk of regimen-related toxicity.

Cyclophosphamide↗

PubMed2000

[CADASIL: clinical analysis of CADASIL and CADASIL-like disorders in Japan].

To clarify the characteristics of CADASIL in Japan, we performed clinical and genetic investigations for six patients from 5 Japanese families diagnosed as CADASIL. We identified that the onset of focal neurologic deficits ranged from 38 to 63 years old (mean 49 +/- 9.4 yrs) and the occurrence rates of main neurologic symptoms and signs were 1/6 for migraine, 3/6 for recurrent stroke episodes, 6/6 for dementia, and 4/6 for pseudobulbar palsy. The marked narrowing of retinal arteries were observed in 3/6. The notch 3 mutations were all found in exon 4. Although other several families shared similar phenotype of CADASIL, there were no deposition of granular osmiophilic materials within the basal lamina of smooth muscle cells in the arterioles of biopsied muscle and no mutations in the cording regions of notch 3 gene. We investigated prospectively the incidence of CADASIL and CADASIL-like disease in Kumamoto district from 1999 to 2000. One thousand and thirty four patients with stroke were hospitalized in 6 hospitals which have stroke care unit. Among them, 7 patients fulfilled the criteria that were less than 60 years old, lacunar strokes and/or TIA, presence of a family history, and no risk factors such as hypertension, diabetes mellitus, and hyperlipidemia. One of seven patients was diagnosed as CADASIL by DNA analysis. It was suspected the incidences of CADASIL and CADASIL-like disease were not so rare in Japan.

Cerebral Infarction↗

PubMed1999

Molecular cloning of a cDNA encoding mouse A15, a member of the transmembrane 4 superfamily, and its preferential expression in brain neurons.

A15, a member of the transmembrane 4 superfamily (TM4SF), was isolated by differential screening of the cDNAs that are preferentially expressed on immature T cells. As a first step in the study of the biological function of the A15 molecule, we isolated cDNAs encoding the entire coding region of mouse A15. Nucleotide sequence analysis of the cDNAs revealed that mouse A15 shares 97% amino acid sequence identity with its human counterpart. The mouse A15 protein product has not yet been characterized, but is predicted to be 244 amino acids with four hydrophobic domains. Northern blot analysis of the RNA samples from various mouse tissues disclosed that the A15 transcripts are expressed most strongly in the brains, and are detectable in the colon, muscle, heart, kidney, and spleen. In situ hybridization of the mouse brain with ribo-probe established that the A15 transcripts are expressed primarily in neurons of the frontal cortex, olfactory bulb, dentate gyrus, caudoputamen, and CA3 region of the hypothalamus as well as in Purkinje cells in the cerebellar cortex, which strongly suggests that A15 may have a special function in the fundamental neuronal functioning of the higher nervous system.

Amino Acid Sequence↗

PubMed1999

2-Phenylquinoline-Carbohydrate Hybrids: Molecular Design, Chemical Synthesis, and Evaluation of a New Family of Light-Activatable DNA-Cleaving Agents.

Artificial intercalator-carbohydrate hybrids such as that shown in the scheme cleave DNA at the site of guanine on irradiation with UV light with a long wavelength. The hybrids also exhibit strong cytotoxicity when irradiated. The hybrid system is very important for DNA cleavage, and the cytotoxic activity correlates with the DNA-cleaving capacity

Journal Article↗

PubMed1999

Pig-n, a mammalian homologue of yeast Mcd4p, is involved in transferring phosphoethanolamine to the first mannose of the glycosylphosphatidylinositol.

Many cell surface proteins are anchored to the membrane via a glycosylphosphatidylinositol (GPI) moiety, which is attached to the C terminus of the proteins. The core of the GPI anchor is conserved in all eukaryotes but is modified by various side chains. We cloned a mouse phosphatidylinositol glycan-class N (Pig-n) gene that encodes a 931amino acid protein expressed in the endoplasmic reticulum, which is homologous to yeast Mcd4p. We disrupted the gene in F9 embryonal carcinoma cells. In the Pig-n knockout cells, the first mannose in the GPI precursors was not modified by phosphoethanolamine. Nevertheless, further biosynthetic steps continued with the addition of the third mannose and the terminal phosphoethanolamine. The surface expression of Thy-1 was only partially affected, indicating that modification of the first mannose by phosphoethanolamine is not essential for attachment of GPI anchors in mammalian cells. An inhibitor of GPI biosynthesis, YW3548/BE49385A, inhibited transfer of phosphoethanolamine to the first mannose in mammalian cells but only slightly affected the surface expression of GPI-anchored proteins. Biosynthesis of GPI in the Pig-n knockout cells was not affected by YW3548/BE49385A, and yeast overexpressing MCD4 was highly resistant to YW3548/BE49385A, suggesting that Pig-n and Mcd4p are targets of this drug.

Animals↗

PubMed1999

Human aiolos, an ikaros-related zinc finger DNA binding protein: cDNA cloning, tissue expression pattern, and chromosomal mapping.

The Ikaros gene (symbol ZNFN1A1) encodes the hematopoietic zinc finger DNA binding protein, which is now recognized as a central regulator of lymphoid differentiation and has been implicated in leukemogenesis. Recently, an Ikaros-related zinc finger protein, called Aiolos (ZNFN1A3), has been identified and characterized, thus establishing the presence of a gene family whose members may be hematopoietic transcription factors. Among Aiolos-mutant mice, development of B-cell lymphoma was frequently seen. As an initial approach to examining the possible involvement of Aiolos in the pathogenesis of human lymphoid proliferative disease, we isolated cDNA clones for human Aiolos from a B-cell cDNA library. The human Aiolos protein predicted from the cDNA sequence consists of 509 amino acid residues and shares 86% sequence identity with its mouse counterpart. As in the case with mouse Aiolos, no isoform for human Aiolos has been found. Northern blot analysis of various human tissues revealed that the Aiolos transcripts are expressed most strongly in peripheral blood leukocytes, the spleen, and the thymus, supporting the notion that Aiolos plays an important role in lymphoid lineages. Fluorescence in situ hybridization using a BAC clone established that the Aiolos gene is mapped to human chromosome band 17q11.2.

Amino Acid Sequence↗

PubMed1999

Different roles of glycosylphosphatidylinositol in various hematopoietic cells as revealed by a mouse model of paroxysmal nocturnal hemoglobinuria.

Patients with paroxysmal nocturnal hemoglobinuria (PNH) have one or a few clones of mutant hematopoietic stem cells defective in glycosylphosphatidylinositol (GPI) synthesis as a result of somatic mutation in the X-linked gene PIG-A. The mutant stem cell clone dominates hematopoiesis by a mechanism that is unclear. To test whether a lack of multiple GPI-anchored proteins results in dysregulation and expansion of stem cells, we generated mice in which GPI-anchor negative cells are present only in the hematopoietic system. We transplanted lethally irradiated mice with female fetal liver cells bearing one allele of the Piga gene disrupted by conditional gene targeting. Because of the X-chromosome inactivation, a significant fraction of the hematopoietic stem cells in fetal livers was GPI-anchor negative. In the transplanted mice, cells of all hematopoietic lineages contained GPI-anchor negative cells. The percentage of GPI-anchor negative cells was much higher in T lymphocytes including immature thymocytes than in other cell types, suggesting a regulatory role for GPI-anchored proteins at an early stage of T-lymphocyte development. However, the proportions of GPI-anchor negative cells in various blood cell lineages were stable over a period of 42 weeks, indicating that Piga mutation alone does not account for the dominance of the mutant stem cells and that other phenotypic changes are involved in pathogenesis of PNH.

Animals↗

PubMed1999

Isolation and characterization of the E2F-like gene in plants.

The transcription factor E2F regulates the expression of genes involved in the progression of G1/S transition and DNA replication in mammalian cells. We cloned and characterized a cDNA (NtE2F) corresponding to a E2F homolog of tobacco (Nicotiana tabacum). The transcription of NtE2F was induced as cells progressed from G1 to the S phase and expressed much earlier than that of the proliferating cell nuclear antigen (PCNA) gene. We demonstrated that NtE2F can interact with the tobacco retinoblastoma (Rb)-related protein in a yeast two-hybrid assay. To further characterize NtE2F, the trans-activation activity of NtE2F was examined by using a transient assay in the tobacco Bright Yellow-2 (BY-2) cells with NtE2F fused to the DNA-binding domain of the veast transcriptional activator GAL4. NtE2F activated the transcription of the beta-glucuronidase (GUS) reporter gene driven by a cauliflower mosaic virus (CaMV) 35S core promoter containing the GAL4-binding sequence. This is the first report of the identification of a functionally equivalent E2F-like gene in plants.

Amino Acid Sequence↗

PubMed1999

Identification and characterization of polycystin-2, the PKD2 gene product.

PKD2, the second gene for the autosomal dominant polycystic kidney disease (ADPKD), encodes a protein, polycystin-2, with predicted structural similarity to cation channel subunits. However, the function of polycystin-2 remains unknown. We used polyclonal antisera specific for the intracellular NH(2) and COOH termini to identify polycystin-2 as an approximately 110-kDa integral membrane glycoprotein. Polycystin-2 from both native tissues and cells in culture is sensitive to Endo H suggesting the continued presence of high-mannose oligosaccharides typical of pre-middle Golgi proteins. Immunofluorescent cell staining of polycystin-2 shows a pattern consistent with localization in the endoplasmic reticulum. This finding is confirmed by co-localization with protein-disulfide isomerase as determined by double indirect immunofluorescence and co-distribution with calnexin in subcellular fractionation studies. Polycystin-2 translation products truncated at or after Gly(821) retain their exclusive endoplasmic reticulum localization while products truncated at or before Glu(787) additionally traffic to the plasma membrane. Truncation mutants that traffic to the plasma membrane acquire Endo H resistance and can be biotinylated on the cell surface in intact cells. The 34-amino acid region Glu(787)-Ser(820), containing two putative phosphorylation sites, is responsible for the exclusive endoplasmic reticulum localization of polycystin-2 and is the site of specific interaction with an as yet unidentified protein binding partner for polycystin-2. The localization of full-length polycystin-2 to intracellular membranes raises the possibility that the PKD2 gene product is a subunit of intracellular channel complexes.

Amino Acid Sequence↗

PubMed1999

Coronary arterial involvement and QT dispersion in Kawasaki disease.

For the early detection of myocardial ischemia in patients with severe involvement of the coronary arteries after Kawasaki disease, a method with high sensitivity and low cost is desirable because these patients require frequent follow-up and diagnostic tests. For this purpose, electrocardiographic, echocardiographic, Holter, and stress testing or angiography are repeated. However, these tests have some limitations due to cost, convenience, or sensitivity. It is uncertain that increased QT dispersion would exactly indicate progression of myocardial ischemia after Kawasaki disease, but this is the first study to present that QT dispersion of > or = 60 ms had higher sensitivity for detection of severe involvement of coronary artery after Kawasaki disease. This study is limited due to the small number of patients; larger prospective studies are required to clarify the usefulness of QT dispersion analysis in detecting the progression of myocardial ischemia after Kawasaki disease.

Adolescent↗

PubMed1999

Diaminodiphenylsulfone resistance of Mycobacterium leprae due to mutations in the dihydropteroate synthase gene.

The nucleotide sequence analysis of the dihydropteroate synthase (DHPS) gene of six diaminodiphenylsulfone-resistant Mycobacterium leprae strains revealed that the mutation was limited at highly conserved amino acid residues 53 or 55. Though the mutation at amino acid residue 55 or its homologous site has been reported in other bacteria, the mutation at residue 53 is the first case in bacteria. This is the first paper which links the mutations in DHPS and sulfonamide resistance in M. leprae. This finding is medically and socially relevant, since leprosy is still a big problem in certain regions.

Dapsone↗

PubMed1999

Neuron-targeted gene transfer by adenovirus carrying neural-restrictive silencer element.

Adenovirus transfers genes to a wide range of cell types, but its application to neurons has been hampered by its reduced efficiency of infection as compared with that for glia. To achieve neuron-targeted gene transfer, we have produced an adenovirus carrying the reporter lacZ gene driven by the SCG10 minimum promoter containing the neural-restrictive silencer element (NRSE), which element selectively represses the transcription of genes in non-neuronal cells. When rat hippocampal slice cultures were infected with NRSE-bearing adenovirus, beta-galactosidase-positive cells were mostly pyramidal and granular neurons, whereas infection with virus carrying a mutated NRSE resulted in beta-galactosidase expression in both neurons and glia. The results suggest that the adenovirus carrying NRSE to be a useful tool for neurontargeted gene transfer.

Adenoviridae↗

PubMed1999

Participation of the pyrazine cation radical in the formation of mutagens in the reaction of glucose/glycine/creatinine.

Two classes of the free radical Maillard intermediates, the pyrazine cation radical and the carbon-centered radicals, are detected in the reaction of Glc (glucose)/Gly (glycine) by electron spin resonance and spin trapping technique. Profile of the generation of the pyrazine cation radical in the reaction with different ratios of the reactants was found to be similar to that of the formation of mutagens in the subsequent reaction with creatinine. By contrast, profile of the generation of the carbon-centered radicals was not consistent with that of the mutagen formation. Thiol antioxidants and unsaturated fatty acids (or their esters) effectively scavenged the pyrazine cation radical generated in the reaction of Glc/Gly, and inhibited the formation of the mutagens in the reaction of Glc/Gly and creatinine. Ethanol, a sulfide and a saturated fatty acid were not effective to scavenge the pyrazine cation radical and did not inhibit the mutagen formation. The pyrazine cation radical rather than the carbon-centered radicals may play an important role in the mutagen formation. Thiol antioxidants and unsaturated fatty acids can be evaluated as inhibitors of the pyrazine cation radical-derived formation of the mutagens.

Cations↗