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Biomedical subjects

T Konno

Publications and source records attributed to T Konno.

At least 91 records · Page 5Linked to original sources
PubMed1996

Surgical simulation of facial paralysis.

We are developing a prototype of a surgical simulation system for restoring facial expression lost in cases of facial paralysis. Correcting facial paralysis requires careful planning of surgery procedures and accurate prediction of the surgical results. So far techniques to perform this task largely relied on the physician's experience, and there were few quantitative data to refer to. The system we propose is finally aimed at helping the surgeon plan the surgery and predict the results. The 3D model of the face used in our system is generated directly from the CT scan of the patient. The face model consists of skin, skull and selected facial muscles based on anatomy. The mass and spring lattice approach is used to give physical attributes to the face model. The present prototype system lets the user directly manipulate graphical representations of facial expression.

Computer Graphics↗
PubMed1996

Cell surface c-kit receptors in human leukemia cell lines and pediatric leukemia: selective preservation of c-kit expression on megakaryoblastic cell lines during adaptation to in vitro culture.

We produced a monoclonal antibody MTK1 which recognized c-kit protein. Using MTK1, 31 leukemia cell lines and 76 leukemia blasts from pediatric patients were analyzed for expression of the c-kit receptor by flow cytometry. The c-kit receptor was detectable on four of four cell lines assigned to the megakaryo/erythromegakaryoblastic lineage and on one of seven cell lines of myeloid lineage. C-kit expression was not seen on any of 20 cell lines of erythroid and lymphoid lineages. Furthermore, c-kit was expressed on 16 of 24 nonlymphoid blasts without platelet surface antigens (67%) and on six of eight non-lymphoid blasts with platelet surface antigens (75%), but was not detectable on 44 lymphoid blasts from pediatric leukemia patients. In these cases CD34 was expressed on 26 of 32 myeloid blasts (81%) and on 27 of 44 lymphoid blasts (61%). The findings indicate a dominant expression of the c-kit receptor on established cell lines assigned to the megakaryo/erythromegakaryoblastic lineage, though a high percentage of leukemic myeloblasts also expressed the c-kit receptor on their surface.

Antibodies, Monoclonal↗
PubMed1996

Antitumor activity of zinostatin stimalamer (YM881) in human hepatoma cell lines and VX2 liver tumor-bearing rabbits.

Antitumor activities of zinostatin stimalamer (YM881) were examined in human hepatoma cell lines (SK-Hep1 and HuH2) and VX2 liver tumor-bearing rabbits. YM881 inhibited the growth of human hepatoma cells in a dose-dependent manner. The IC50 values of YM881 causing a 50% inhibition of growth of SK-Hep1 and HuH2 cells were 6.7 and 27 nM, respectively. In VX2 tumor-bearing rabbits, administration of YM881 suspended in Lipiodol, an iodinated fatty acid ethylester of poppyseed oil, (YM881/Lipiodol suspension, 0.2 mg/0.2 ml/body) into the hepatic artery showed significant (p < 0.01, vs. sham-operated and Lipiodol-treated groups) inhibitory effects on tumor growth and histopathological changes at 1 and 2 weeks after administration. In contrast, Lipiodol (0.2 ml/body) tended to inhibit the growth of VX2 tumor (p < 0.1, vs. sham-operated group) at 1 week after administration, but showed only moderate effects at 2 weeks after administration. Minimal necrosis was observed at 1 and 2 weeks after administration of Lipiodol, and histopathological findings were similar to those in the sham-operated group. From the present study, it is suggested that YM881/Lipiodol suspension showed antitumor activity in VX2 tumor-bearing rabbits presumably due to the inhibition of the growth of hepatoma cells by YM881 itself. Lipiodol, on the other hand, is considered to augment the antitumor activity of YM881 by maintaining high YM881 concentrations in tumor tissue.

Animals↗
PubMed1996

[Identification of mutations that were responsible for primary immunodeficiency diseases].

The genes responsible for many X-linked and autosomal recessive primary immunodeficiency diseases have been identified during the past two years. Now we can diagnose more than a dozen primary immunodeficiency diseases by genetic methods as well as immunological ones. We describe here two patients with leukocyte adhesion deficiency (LAD) and with X-linked agammaglobulinemia (XLA) the diagnoses of which were confirmed by genetic analysis. A patient with LAD showed a missense mutation of the CD18 gene from C to T at nucleotide position 605 resulting in a proline178-->leucine substitution. The mutation of the other allele has not yet been analyzed, because few CD18 mRNAs were translated from the mutated DNA. Another patient with XLA had a missense mutation of Btk gene at position 1204 of C to T resulting in a change of leucine358-->phenylalanine. In view of the mutation of the Sac I restriction site from GAGCTC to GAGTTC we can easily differentiate patients and the carrier from normal persons by the amplification of genomic Btk DNA. Through these studies unknown functions of these genes will be clarified in the near future.

Agammaglobulinemia↗
PubMed1996

[Targeted chemotherapy of hepatocellular carcinoma using Lipiodol as a carrier].

For targeted chemotherapy using Lipiodol as a carrier, it was found that anticancer agents had to be dissolved in Lipiodol and diffused gradually from it. Dose forms having properties for targeted chemotherapy were named "oily anticancer agents". Oily anticancer agents are completely different from simple mixture of Lipiodol and anticancer agents by pumping methods in antitumor activities and adverse effects. Up to 1,601 arterial injections of oily anticancer agents were given to 400 patients with unresectable hepatocellular carcinoma. Decrease in serum AFP levels was observed in 209 (94%) of 222 AFP-positive patients, and reduction of tumor size was observed in 308 (96%) of 322 patients who had evaluable tumors. Reduction in size to less than 50% was observed in 50% of patients 5 to 6 months after initial administration, and all tumors reduced to less than 50% one year after. In 45 of 60 patients whose tumors shrank to less than 10% of initial size, follow-up 1 year or more after tumor shrinkage could be done (range 1-9 years, average 3 years). These tumors did not regrow, so they were considered to be cured. Survival was prolonged, especially in 251 patients who were good candidates for therapy (excluding those with Child C liver cirrhosis, tumor occupying all four segments of the liver, and/or extrahepatic spread at initial arterial injection of the drug), the 1-, 2-, and 5-year survival rates were 83, 58, and 34%, respectively.

Adolescent↗
PubMed1995

Solution X-ray scattering analysis of cold- heat-, and urea-denatured states in a protein, Streptomyces subtilisin inhibitor.

Streptomyces subtilisin inhibitor (SSI), a homo-dimeric protein with a subunit of 113 residues with two disulfide bonds, is known to exist at low pH in at least three distinct thermodynamic states namely, the native (N), cold-denatured (D') and heat-denatured (D). Small-angle X-ray scattering was used to analyze and to compare overall chain conformations of SSI in typical, N, D', D and urea-denatured states (Durea). Molecular masses were determined from scattering intensities extrapolated to a scattering angle of zero, which showed that SSI exists as a homo-dimer in the N state, but as dissociated monomers in the D', D and Durea states. From Guinier plots of the scattering intensities, radii of gyration (Rg) were determined to be 20.1(+/- 1.8) A for N, and 20.7(+/- 1.3), 25.8(+/- 1.5) and 32 to 35 A for D', D and Durea, respectively. Kratky plots for both N and D' exhibited a bell-shape indicating that the polypeptide chain has a globular part not only in N but also in D', while Kratky plots for D and Durea showed that the polypeptide chain has no globular part either in Durea or D. Combined with the results from circular dichroism and 1H NMR spectra, a picture emerges for the polypeptide chain conformation of SSI such that in N it is a globular dimer close to that in the crystal, in Durea it is totally disordered and expanded nearly to a fully random chain with restrictions only from the disulfide bridges, in D the entire chain is disordered and expanded but with considerable local intra-chain interactions, and in D' the chain consists of a part with a unique tertiary structure and a part disordered and expanded to a degree comparable to D.

Bacterial Proteins↗
PubMed1995

Identification of a highly specific surface marker of T-cell acute lymphoblastic leukemia and neuroblastoma as a new member of the transmembrane 4 superfamily.

Five monoclonal antibodies detected a surface antigen expressed exclusively on T-cell acute lymphoblastic leukemia (T-ALL) in a panel of 45 human hematopoietic cell lines, including T-cell lines derived from adult T-cell leukemia and those established by immortalization with human T-cell leukemia virus type 1 or Herpesvirus saimiri. Peripheral blood mononuclear cells, including fresh and activated T cells, were also completely devoid of this antigen. We designated this antigen as TALLA-1 (from T-ALL-associated antigen 1). By expression cloning, a cDNA clone encoding TALLA-1 was isolated from T-ALL cell line Molt-4. TALLA-1 was found to be a member of the transmembrane 4 superfamily (TM4SF). The cDNA was also essentially identical to A15, which was isolated from another T-ALL cell line, HPB-ALL, by differential hybridization with normal peripheral blood lymphocytes, and to CCG-B7, which was isolated from a brain cDNA library using CCG repeat as a probe. The gene product was now characterized in detail at the protein level. Northern blot analysis showed that the gene was expressed most strongly in brain, skeletal muscle and spleen. In a panel of 52 non-hematopoietic human cell lines, the majority of neuroblastoma cell lines were found to be positive for TALLA-1. Like ME491, CO-029 and L6, TALLA-1 may be another TM4SF member behaving as a potential tumor-associated antigen.

Amino Acid Sequence↗
PubMed1995

Problems of neuroblastoma screening for 6 month olds and results of second screening for 18 month olds.

Nationwide neuroblastoma mass screening for 6-month-old infants (first screening) was introduced in Japan in 1985. About 110 neuroblastoma cases are detected annually by the first screening and treated, with a survival rate of 97%. Sensitivity of the first screening (positive cases/positive cases+false negative cases) is about 75%, and the prognosis of false-negative cases is unfavorable. A second screening at 18 months of age was started to rescue false-negative cases in Miyagi Prefecture in May 1992. Of 62 neuroblastoma cases treated in our hospital since 1985, 40 cases had received the first screening. Twenty cases were positive at first screening, 18 cases were false negative, and 2 cases were false negative and picked up by the second screening. Age distribution of false-negative cases ranged from 12 to 83 months and included 12 cases younger than 36 months old. Only 5 of 18 false-negative cases are alive without the disease. From May 1992 to November 1993, 14,282 infants had received the second screening (compliance rate: about 75%), and 2 neuroblastoma cases were detected. The first case was stage III with paraortic lymph node metastases, Shimada UH, aneuploidy and negative N-myc amplification. The second case was stage II with Shimada FH, aneuploidy, and negative N-myc amplification. Both cases are alive now without the disease after undergoing radical operation and chemotherapy. The first screening is effective for early detection of neuroblastoma cases, but the sensitivity is insufficient; the authors recommend a second screening to rescue false-negative cases.

Adrenal Gland Neoplasms↗
PubMed1995

A human CD4- CD8- T-cell receptor alpha beta + T leukemic cell line undergoing phytohemagglutinin-induced apoptosis.

A human CD4- CD8- alpha beta T-cell receptor (TCR alpha beta)+ T leukemic cell line, L-KAW, was established from the peripheral blood of a 6-year-old male patient with T-cell acute lymphoblastic leukemia. Its phenotype was found to be CD7+CD2+CD3+CD4-CD8- TCR alpha beta +. The cell line proved susceptible to killing by exposure to a mitogenic concentration of phytohemagglutinin (PHA) within several hours, with biochemical analyses demonstrating extensive degradation of DNA to oligonucleosomal bands characteristic of apoptosis. Chromatin condensation and cell shrinkage features of apoptotic cells could also be clearly identified under the electron microscope. The apoptosis-related Fas antigen was expressed on L-KAW cells and DNA fragmentation was induced by incubation with anti-Fas monoclonal antibody. The c-myc mRNA levels declined within 15 min to 3 h after the addition of PHA. These results suggest that L-KAW cells are specifically sensitive to induction of apoptosis in response to PHA without preactivation. They may, therefore, be considered an analog of activated T-cells and prove useful as a model system for characterizing biochemical and molecular mechanisms underlying the process of this type of cell death.

Antibodies↗
PubMed1995

Preliminary preformulation studies of a 2-(3,4-dimethoxyphenyl)ethylamine derivative for oral administration at an exploratory stage of new drug development.

Preliminary preformulation studies of a 2-(3,4-dimethoxyphenyl)ethylamine derivative were investigated. The hydrochloride form showed incompatibility with the excipients used for oral dosage forms. There were several crystal forms of the free base, namely, alpha-anhydrate, beta-anhydrate, monohydrate, and trihydrate. The trihydrate form was unstable. The degree of crystallinity of the beta-anhydrate form was difficult to control. The monohydrate form was difficult to manufacture with constant quality. The serum levels of the compounds in rats were almost related to the dissolution rates in the JP 1st disintegration medium from the discs. The serum level of alpha-anhydrate was the lowest. However, the dissolution rates from the formulations of alpha-anhydrate were improved. After oral administration of the improved formulation, the serum level of alpha-anhydrate in beagle dogs was almost triple that after the oral administration of the capsule of the hydrochloride form.

Administration, Oral↗
PubMed1995

Polysaccharide (ANK-102) from Polianthes tuberosa cells deteriorates the resistance of mice to Listeria monocytogenes infection.

Modulatory effect on the murine self defense system by a newly discovered acidic polysaccharide (ANK-102) produced by P. tuberosa cells in liquid culture was examined. Pretreatment with ANK-102 deteriorated the murine survival against lethal infection of Listeria monocytogenes, an intracellular gram-positive bacterium eliminated mainly by macrophages through T-cell mediated immune response. Pretreatment with ANK-102 resulted in the accumulation of Mac 1 and Mac 2 positive cells in the peritoneal cavity of the infected animals and the reduction of Thy1.2 expression on the surface of the thymocytes. A new type of immunosuppressive polysaccharide ANK-102 was introduced.

Animals↗
PubMed1995

[Rehabilitation in rheumatoid arthritis (RA) patients--assessment of effects of rehabilitation based on activities of daily living (ADL)].

The 37 hospitalized RA patients undergoing rehabilitation (for 4 weeks) were evaluated on effects of rehabilitation by comparing scores of ADL at the time of admission and discharge. Items of ADL were composed of 32. Items of ADL which were likely to be disabled were related to those of ADL which were influenced by rehabilitation (r = 0.7412, p < 0.01). From this result, 11 items of ADL which were likely to be disabled and influenced by rehabilitation could be selected in order. Usefulness of these selected items of ADL on evaluation of rehabilitation was admitted.

Activities of Daily Living↗
PubMed1995

Clinical significance of antiphospholipid antibodies in fulminant hepatic failure.

We examined the incidence of antiphospholipid antibodies (APA) in patients with fulminant hepatic failure (FHF) and various liver diseases using the enzyme-linked immunosorbent assay (ELISA), and assessed possible correlations with the pathophysiology of these diseases. The APA assay employed cardiolipin (CL), phosphatidylserine (PS), and phosphatidylinositol (PI) as antigens. Anti-CL IgA antibody was detected in 13/14 (92.9%) patients with FHF. The incidence of anti-CL-IgG, anti-CL-IgM, anti-PS-IgG, and anti-PI-IgG was 14.3%, 35.7%, 64.3%, and 71.4%, respectively. Despite the high incidence of APA in FHF, these antibodies were not detected in most patients with acute or chronic hepatitis. There was a negative correlation between anti-CL-IgA and the platelet count, and a negative correlation between anti-PI-IgG and the amount of residual liver parenchyma. Our results suggest that APA develop secondarily to hepatocyte or sinusoidal cell damage and may aggravate both thrombocytopenia and liver failure.

Adult↗
PubMed1994

Erythropoietin-dependent induction of hemoglobin synthesis in a cytokine-dependent cell line M-TAT.

M-TAT is a cytokine-dependent cell line with the potential to differentiate along the erythroid and megakaryocytic lineages. We cultured M-TAT cells long term (> 1 year) in the continuous presence of erythropoietin (EPO), granulocyte-macrophage colony-stimulating factor (GM-CSF), or stem cell factor (SCF). These long term cultures are referred to as M-TAT/EPO, M-TAT/GM-CSF, and M-TAT/SCF cells, respectively. Hemoglobin concentration and gamma-globin and erythroid delta-aminolevulinate synthase mRNA levels were significantly higher in M-TAT/EPO cells than in M-TAT/GM-CSF cells. When the supplemented cytokine was switched from GM-CSF to EPO, hemoglobin synthesis in M-TAT/GM-CSF cells increased rapidly (within 5 h), and the level of GATA-1 mRNA increased. In contrast, the addition of GM-CSF to the M-TAT/EPO cell culture decreased the amount of hemoglobin, even in the presence of EPO, indicating that the EPO signal for erythroid differentiation is suppressed by GM-CSF. Thus, erythroid development of M-TAT cells is promoted by EPO and suppressed by GM-CSF. These results support the hypothesis that EPO actively influences the programming of gene expression required for erythroid progenitor cell differentiation.

5-Aminolevulinate Synthetase↗
PubMed1994

Impairment of ligand binding and growth signaling of mutant IL-2 receptor gamma-chains in patients with X-linked severe combined immunodeficiency.

The IL-2R gamma-chain is an indispensable subunit for the functional IL-2R. Recently, mutations of the gamma-chain have been reported to be closely associated with X-linked severe combined immunodeficiency (XSCID). The present study reveals that three patients with XSCID have three different mutations in the gamma-chain; a point mutation, a two consecutive-base deletion, and lack of the second exon in mRNA. The point mutation that we have detected is C to T, which results in one amino acid substitution of valine for alanine in the extracellular domain of the IL-2R gamma-chain (named AV mutant). The two-base deletion detected causes a frame shift of the coding region in the SH2 subdomain in the cytoplasmic domain (named tSH mutant). Transfection studies performed with the mutant gamma-chains demonstrated that the AV mutant and tSH mutant failed to bind to IL-2 and to transduce growth signals, respectively. These findings indicate that the gamma-chain gene mutations that accompany XSCID induce loss of the gamma-chain function, possibly resulting in stagnation of the differentiation and development of T cells.

Base Sequence↗