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Biomedical subjects

M Takeuchi

Publications and source records attributed to M Takeuchi.

At least 217 records · Page 12Linked to original sources

[An successful case of combined daily oral administration of UFT and low-dose etoposide for multiple metastases of lung cancer].

The authors treated a 49-year old female patient, who had multiple metastases of lung cancer, by combined daily oral administration of UFT and low-dose ETP. She was admitted to our hospital due to complaints of cough and dyspnea, and multiple nodular shadows were seen in both lungs on chest X-rays. The pulmonary lesion was diagnosed as pulmonary metastasis of lung cancer (squamous cell car) by lung biopsy under CT-guide. She also had bone metastasis of the ribs and cerebellar metastasis from the lung cancer. Combination chemotherapy of UFT 300 mg/body daily and etoposide 25 mg/body daily was performed for 13 months. The pulmonary metastatic tumors were reduced significantly. No side effects of the carcinostatic agents were noted. She is now doing well. Combined daily oral administration of UFT and low-dose etoposide is considered to be safe and effective, and the treatment useful for recovering QOL in advanced lung cancer patients.

Administration, Oral↗

Effects of "isolating hemodialysis" on prevention of methicillin-resistant Staphylococcus aureus cross-infection in a hemodialysis unit.

AIM: To evaluate the effects of a contact isolation program against methicillin-resistant Staphylococcus aureus (MRSA) cross-infection among patients in a hemodialysis unit. CLINICAL SETTING AND METHODS: In all patients maintaining hemodialysis therapy were tested for MRSA infection and who had MRSA infection, not only inpatients but also outpatients were separated into a designated area (isolating hemodialysis). Clinically isolated MRSA strains were clonotyped with coagulase typing, staphylococcal enterotoxin typing and restriction enzyme analysis of plasmid DNA. RESULTS: The frequency of patients with MRSA infection was 4.5% before starting this protocol and was reduced to 2.9% two and a half years later. At this time, MRSA was isolated from the 8 patients. These 8 clinical strains were differentiated into 6 clonotypes and 3 strains showed the same patterns. Two of 3 were isolated from inpatients and the other was from a patient with community onset MRSA colitis. In this case, most MRSA infections were independent under prophylaxis control and cross-infection was observed only once between hospitalized patients who stayed in a same ward. CONCLUSION: This "isolating hemodialysis" should be useful to prevent cross-infection among patients in end-stage renal disease in a dialysis unit.

Adult↗

[Significance of interferon alpha therapy for advanced renal cell carcinoma. Fukushima Renal Cancer Study Group].

We ranked prognostic factors to retrospectively evaluate the clinical significance of interferon alpha (IFN-alpha) therapy in patients with Robson stage IVB renal cell carcinoma. A total of 44 Robson stage IVB renal cancer patients were divided into 2 groups, one with more than 6 months administration of IFN-alpha (3-7 times a week: group A) and another without any IFN-alpha administration. The distribution of these 2 groups was not randomized. In addition to IFN-alpha therapy, survival was analyzed with respect to performance status (PS), mass reductive nephrectomy, concomitant use of other cytotoxic therapies, the number of metastatic organs, growth type, site of metastasis and the period of diagnosis, using a multivariate method with Cox proportional hazards regression. The multivariate analysis showed administration of IFN-alpha to be the most significant factor influencing a good prognosis. Improved survival was also significantly correlated with slow growing type and good PS. Among group A, a significant favorable prognosis was obtained in patients with the responses of no change (NC), partial response (PR) and complete remission (CR) 6 months after initiating administration of IFN-alpha, as well as with good PS and a slow growing type carcinoma. We conclude that IFN-alpha therapy might improve the prognosis of patients with Robson stage IVB renal cell carcinoma, especially, in cases when a greater than NC response is obtained after 6 months administration of IFN-alpha.

Aged↗

[Atopic dermatitis at 18-months physical examination].

In order to know the prevalence rate and severity of atopic dermatitis, and to compare them to those previously done for 4-month-old infants, the authors examined atopic dermatitis of 18-month-old children at regular health checks at a health center. Among 769 children examined, 69 were diagnosed as having atopic dermatitis, giving a prevalence rate of 9.0%. Most of cases were mild, and no severe cases were observed. In contrast to the location of eruptions on head, face, and trunk at 4-month-old, the eruptions were seen mainly on the trunk and extremities. The prevalence rate in summer and autumn was significantly lower than that in winter and spring. Among 501 children whom we could examine both at 4-month and 18-month-old, 102 cases were diagnosed as having atopic eruptions at 4 months. The eruptions, however, were disappeared in 83 cases when they were 18-month-old. The severity of atopic dermatitis also came to be mild when they grew up. Altogether, a quarter of children had atopic eruptions either at 4 months or 18 months, or both. It will be of interest to observe the transition of atopic dermatitis in childhood and we are planning to follow them at next physical examination at 3-year-old.

Dermatitis, Atopic↗

[A case of terminal cancer patient whom the home staying terminal cares were provided with ease supported by the regional core hospital].

A physician who practices generally at his private clinic will be sometimes referred to a cancer patient staying at home. This referral is hardly acceptable without helps from other medical and paramedical specialities. He needs a support organization in which a supporting hospital is the most important. A case of home staying terminal cancer patient is reported here whom a private practician provided terminal cares with great difficulties at the beginning and afterwards with no significant difficulties organizing a care team for the home staying patient and assisted by a supporting hospital.

Aged↗

[Home infusion therapy system from a resident's point of view].

We started a new home infusion therapy system in July 1999. The home infusion therapy system is made up of doctors, nursing stations, and pharmacies in the community. We coordinate these parties before patient discharge from our hospital and support them when the patient needs hospitalization (for example, he or she develops pneumonia). This report discusses past experiences and future issue.

Home Care Services, Hospital-Based↗

[Pulmonary Nocardia otitidiscaviarum infection in an immunocompetent host].

A rare case of pulmonary Nocardia otitidiscaviarum (N. otitidiscaviarum) was encountered in an immunocompetent host. A 74-year-old man was admitted to our hospital with a high fever and a productive cough. His chest radiograph and CT scan revealed infiltrative shadows in the right middle and lower lung fields. Although several antibiotics (third-generation cephalosporin, minocycline, imipenem) were administered, the fever and cough persisted, and C-reactive protein remained elevated. Repeated sputum cultures showed normal flora, so a transbronchial lung biopsy and bronchoalveolar lavage (BAL) were performed bronchoscopically at the right S5. The BAL fluid contained acid-fast, branching filamentous structures. The microorganism was identified as N. otitidiscaviarum by the Research Center for Pathogenic Fungi and Microbial Toxicoses (Chiba University). Trimethoprim-sulfamethoxazole was therefore administered, but the fever continued to rise daily, and C-reactive protein remained elevated. This isolated N. otitidiscaviarum showed resistance to multiple antimicrobial agents in vitro when examined by the disk diffusion method, and so, on the basis of the antibiogram, the patient was treated with clarithromycin (oral, 600 mg/day) plus amikacin (400 mg/day), which proved successful. Testing for pulmonary nocardiosis should be added to the differential diagnosis procedures for refractory pneumonia as an opportunistic infection and for community-acquired pneumonia.

Aged↗

Good prognosis of patients with acute promyelocytic leukemia who achieved second complete remission (CR) with a new retinoid, Am80, after relapse from CR induced by all-trans-retinoic acid.

A new synthetic retinoid, Am80, is effective in treating acute promyelocytic leukemia relapsed from all-trans-retinoic acid-induced complete remission (CR). We report here the long-term clinical outcomes of patients who achieved second CR with Am80. Of 24 evaluable patients, 14 achieved a second CR by Am80 therapy. Of those patients, 4 relapsed within 6 months, despite subsequent consolidation chemotherapy. Six patients underwent sibling or unrelated HLA-matched allogeneic bone marrow transplantation (BMT), and 4 are alive without relase for more than 49 months after achieving second CR. Four of 8 patients who did not receive BMT are alive without relapse for more than 49 months. Promyelocytic leukemia-retinoic acid receptor alpha (PML-RAR alpha) fusion transcript was undetectable by reverse transcriptase-polymerase chain reaction in all living patients. Therefore, if patients achieve second CR with Am80 and HLA-matched donors are available, BMT is the treatment of choice. However, it is noteworthy that CR was maintained for more than 49 months in half of the patients who did not receive BMT.

Adult↗

[Four cases of the anomalous origin of the left coronary artery from the pulmonary artery].

We report perioperative management of 4 patients with anomalous origin of the left coronary artery from the pulmonary artery. This report involves with 3 infant cases and an adult. Two infants underwent coronary reimplantation procedure and Takeuchi's method was performed on the other infant. In all infant cases, mitral valve plasty was performed to correct mitral regurgitation secondary to papillary muscle dysfunction. The adult patient underwent CABG with ligation of LCA. General anesthesia was performed with high doses of fentanyl in all cases. We employed a relatively high PaCO2 and low FIO2 in order to maintain a high pulmonary vascular resistance. It aims to decrease the incidence of left to right shunt. We used epinephrine to wean one infant and the adult from cardiopulmonary bypass. Perioperative course was uneventful with the use of catecholamines and high doses of vasodilators for left ventricular dysfunction and coronary perfusion under mechanical ventilation.

Anesthesia, General↗

[Acquired immunodeficiency syndrome-associated progressive multifocal leukoencephalopathy treated with highly active anti-retroviral therapy].

We reported a patient with acquired immunodeficiency syndrome (AIDS)-associated progressive multifocal leukoencephalopathy (AIDS-PML), whose condition improved after highly active anti-retroviral therapy (HAART). A 70-year-old man was admitted to our hospital because of worsening left hemiplegia and disturbance of consciousness. During the past 30 years, he frequently traveled to the United States and southeast Asia. On neurological examination, he was somnolent and left hemiplegia with severe rigospasticity was present. The deep tendon reflexes showed hyper-reflexes with extensor plantar responses. Laboratory studies showed pancytopenia and positive HIV-1 antibodies. The CD4 cell count was 38/mm3 and his HIV viral RNA load in the blood was 9,500 copies/ml. T2-weighted magnetic resonance imaging (MRI) of the brain revealed asymmetrical high intensity white matter lesions in the right fronto-parietal, and left frontal regions and in the cerebellar hemisphere. The cerebrospinal fluid (CSF) protein elevated to 91 mg/dl with a normal cell count. The diagnosis of PML was confirmed by the detection of JC virus DNA in the CSF using a nested polymerase chain reaction assay. Three weeks after starting HAART with zidovudine, lamivudine, and indinavir, he was able to respond to simple commands. Two months later, the HIV viral RNA load decreased to less than 400 copies/mm3, and no JC virus DNA was detected in the CSF, with an increase of the CD4 cell count to 285/mm3 in the blood. A follow-up MRI of the brain showed a reduction in the cerebellar and cerebral white matter lesions. The recovering immune function by decreasing of the HIV load after HAART might suppress JC virus replication. It was suggested that HAART would become a beneficial treatment for patients with AIDS-PML.

Acquired Immunodeficiency Syndrome↗

Syntheses and evaluation of amidinobenzofuran derivatives as tryptase inhibitors.

We report the syntheses and evaluation of amidinobenzofuran derivatives as tryptase inhibitors. Among the compounds we evaluated, 1,5-Bis[4-(5-amidinobenzofuran-2-ylcarbonyl)piperazinylca rbonylmethoxy]cyclooctane 26 (AY0068) was found to be a selective and potent non-peptide inhibitor. 26 was effective in PCA reaction in rats without showing antihistaminic activity.

Animals↗

nArgBP2, a novel neural member of ponsin/ArgBP2/vinexin family that interacts with synapse-associated protein 90/postsynaptic density-95-associated protein (SAPAP).

Postsynaptic density (PSD)-95/synapse-associated protein (SAP) 90 and synaptic scaffolding molecule (S-SCAM) are synaptic membrane-associated guanylate kinases. Both the proteins interact with SAP90/PSD-95-associated protein (SAPAP) (also called guanylate kinase-associated protein/Dlg-associated protein). SAPAP is a protein highly enriched in the PSD fraction and may link PSD-95/SAP90 and S-SCAM to Triton X-100-insoluble structures. We found here a novel SAPAP-interacting protein, which was specifically expressed in neural tissue and was present in the postsynaptic density fraction in brain. This protein had a sorbin homology domain in the N terminus, a zinc finger motif in the middle region, and three src homology (SH) 3 domains in the C terminus and was homologous to the ponsin/ArgBP2/vinexin family proteins. We named this protein nArgBP2 because it was the most homologous to ArgBP2. nArgBP2 is a neural member of a growing family of SH3-containing proteins. nArgBP2 bound to the proline-rich region of SAPAP via its third SH3 domain and was coimmunoprecipitated with SAPAP from the extract of rat brain. Furthermore, nArgBP2 was colocalized with SAPAP at synapses in cerebellum. nArgBP2 bound to not only SAPAP but also vinculin and l-afadin, known to bind to ponsin and vinexin. nArgBP2 may be implicated in the protein network around SAPAP in the PSD.

Adaptor Proteins, Signal Transducing↗

Structure, pathology and function of the N-linked sugar chains of human chorionic gonadotropin.

Human chorionic gonadotropin (hCG) contains five acidic N-linked sugar chains, which are derived from three neutral oligosaccharides by sialylation. Each of the two subunits (hCGalpha and hCGbeta) of hCG contain two glycosylated Asn residues. Glycopeptides, each containing a single glycosylated Asn, were obtained by digestion of hCGalpha with trypsin, and of hCGbeta with chymotrypsin and lysyl endopeptidase. Comparative study of the sugar chains of the four glycopeptides revealed the occurrence of site-directed glycosylation. Studies of the sugar chains of hCGs, purified from urine of patients with various trophoblastic diseases, revealed that choriocarcinoma hCGs contain sialylated or non-sialylated forms of eight neutral oligosaccharides. In contrast, hCGs from invasive mole patients contain sialyl derivatives of five neutral oligosaccharides. The structural characteristics of the five neutral oligosaccharides, detected in choriocarcinoma hCGs but not in normal placental hCGs, indicate that N-acetylglucosaminyltransferase IV (GnT-IV) is abnormally expressed in the malignant cells. This supposition was confirmed by molecular biological study of GnT-IV in placenta and choriocarcinoma cell lines. The appearance of tumor-specific sugar chains in hCG has been used to develop a diagnostic method of searching for malignant trophoblastic diseases. In addition, a summary of the current knowledge concerning the functional role of N-linked sugar chains in the expression of the hormonal activity of hCG has been presented.

Animals↗

Identification of a novel 300-kDa factor termed IkappaB alphaE3-F1 that is required for ubiquitinylation of IkappaB alpha.

Destruction of IkappaB by ubiquitinylation is required for signal-dependent activation of NF-kappaB. The IkappaB alpha ubiquitin-ligase activity associated with phosphorylated IkappaB alpha (pIkappaB alpha) in HeLa cells was almost completely lost by washing under stringent conditions including 1 M NaCl; nevertheless, an SCF(betaTrCP) complex containing Skp1, Cullin-1, and F-box/WD40 protein betaTrCP was still bound to pIkappaB alpha, suggesting the existence of a putative factor that is loosely associated with pIkappaB alpha and may collaborate with SCF(betaTrCP). The factor was named IkappaB alphaE3-F1 and was partially purified from HeLa cells. Gel filtration analysis revealed that IkappaB alphaE3-F1 has an apparent molecular mass of approximately 300 kDa.

Blotting, Western↗

Synamon, a novel neuronal protein interacting with synapse-associated protein 90/postsynaptic density-95-associated protein.

Guanylate kinase-associated protein (GKAP)/SAP90/PSD-95-associated protein (SAPAP)/DLG-associated protein (DAP) is a protein of the postsynaptic density (PSD), and binds to the guanylate kinase domain of PSD-95/synapse-associated protein (SAP) 90 and synaptic scaffolding molecule. GKAP/SAPAP/DAP recruits PSD-95/SAP90 and its interacting protein, brain-enriched guanylate kinase-interacting protein, into the Triton X-100-insoluble fraction in transfected cells, suggesting that GKAP/SAPAP/DAP may link several PSD components to the Triton X-100-insoluble structures in the PSD. We have identified here a novel neuronal GKAP/SAPAP/DAP-binding protein and named it synamon. Synamon has seven ankyrin repeats at the NH(2) terminus followed by one src homology 3 domain and one PSD-95/Dlg-A/ZO-1 domain, and several proline-rich regions at the carboxyl terminus. Synamon interacts with the COOH-terminal region of GKAP/SAPAP/DAP via the middle region containing a PSD-95/Dlg-A/ZO-1 domain. Synamon was coimmunoprecipitated with SAPAP from rat crude synaptosomes and colocalized with SAPAP in primary cultured rat hippocampal neurons. Because synamon is composed of various protein-interacting modules, it may also interact with proteins other than GKAP/SAPAP/DAP to organize the architecture of the PSD.

Adaptor Proteins, Signal Transducing↗

Interleukin-18 induces interferon-gamma production through NF-kappaB and NFAT activation in murine T helper type 1 cells.

Interleukin-18 (IL-18) combined with anti-CD3 monoclonal antibody (mAb) induced interferon-gamma (IFN-gamma) production by T helper type 1 (Th1) cells. Neither IL-18 nor anti-CD3 mAb alone induced production of IFN-gamma. Although treatment with IL-18 alone induced full activation of NF-kappaB in Th1 cells, it was not sufficient for the production of IFN-gamma. To examine the importance of NF-kappaB activation in IFN-gamma production, we established Th1 cells which expressed a transdominant IkappaBalpha mutant. In these cells, activation of NF-kappaB and production of IFN-gamma by IL-18 were suppressed. On the other hand, we examined the T cell receptor (TCR)/CD3-mediated signaling pathway. FK506, an inhibitor of NFAT activation, inhibited IFN-gamma production by IL-18 without any effect on the NF-kappaB activation. We conclude that dual signaling consisting of IL-18-induced NF-kappaB activation and TCR/CD3-mediated NFAT activation is crucial for IFN-gamma production by IL-18 in murine Th1 cells.

Animals↗

Unusually high expression of N-acetylglucosaminyltransferase-IVa in human choriocarcinoma cell lines: a possible enzymatic basis of the formation of abnormal biantennary sugar chain.

Structural analysis of the sugar chains of human chorionic gonadotropin (hCG) has revealed that abnormal biantennary structures appear specifically on hCG in the urine of choriocarcinoma patients. However, the enzymatic and molecular mechanisms of the biosynthesis of abnormal biantennary sugar chains have not yet been elucidated. In this report, the enzyme activities and the expression levels of mRNAs of N-acetylglucosaminyltransferases (GnT)-I to -V, beta-1,4-galactosyltransferase, and alpha-mannosidase II in normal human placentae and three human choriocarcinoma cell lines were investigated. GnT-IV activities in choriocarcinoma cell lines were increased from 16- to 66-fold and GnT-III activity was increased from 15- to 25-fold as compared with those in human placentae, whereas other enzyme activities were not increased significantly. The mRNA expression levels generally correlated with their enzyme activities. Among the two GnT-IV genes found in human tissues only GnT-IVa gene was strongly expressed in the cancer cells: from three to seven times as much as in the normal tissue, whereas that of GnT-IVb remained constant. On the basis of these results, we proposed that ectopic expression of GnT-IVa gene should occur along with the malignancy of trophoblastic tissues, and that the increased GnT-IV activity should be the main cause of the formation of abnormal biantennary sugar chains in choriocarcinoma. A possible enzymatic basis of the biosynthesis of abnormal biantennary sugar chains is discussed.

Carbohydrate Metabolism↗