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Biomedical subjects

Makoto Takeuchi

Publications and source records attributed to Makoto Takeuchi.

At least 19 recordsLinked to original sources
PubMed2004

[Clinical evaluation of cefozopran as treatment for febrile neutropenia].

Clinical effects and safety of cefozopran (CZOP) were evaluated by the Okayama Bone Marrow Transplantation Group. Twenty-five patients expected to experience febrile neutropenia during induction chemotherapy or consolidation chemotherapy of acute leukemia were enrolled between July 2000 and November 2002. CZOP was administrated by drip infusion at 4g/day bid for a minimum of 3 days. The clinical effects and safety were evaluated in 20 patients with fever of 37.5 degrees C or more from a clinically suspected infection. The underlying disease was acute myeloid leukemia in 17 patients, acute lymphoid leukemia in 1 and acute promyelogeneous leukemia in 1. The complicating infections were sepsis and suspected sepsis. Clinical efficacy was excellent in 11 patients, good in 1, fair in 2 and poor in 6, with an efficacy rate of 60.0%. The efficacy rate in patients whose albumin levels before therapy were less than 3.8 g/dl was 37.5%, whereas the rate in patients whose albumin levels before therapy were between 3.8 g/dl and 5.3 g/dl was 80.0%. The efficacy rate in patients whose neutrophil counts before therapy were less than 100/microliter was 50.0%, whereas the rate in patients whose neutrophil counts after therapy were less than 100/microliter was 53.8%. The efficacy rate in patients whose neutrophil counts both before and after therapy were less than 100/microliter was 37.5%. Side effect of exanthema was observed in 1 patient. These results indicate that CZOP is an effective and safe antibiotic for the treatment of febrile neutropenia in patients with hematological malignancies.

Acute Disease↗
PubMed2003

Biophysical analyses of the transthyretin variants, Tyr114His and Tyr116Ser, associated with familial amyloidotic polyneuropathy.

The familial amyloidotic polyneuropathy is strictly associated with point mutations in the coding region of the transthyretin gene. Here, we focused on the mutations in the monomer-monomer and dimer-dimer interaction site of the transthyretin tetramer. The naturally occurring amyloidogenic Tyr114His (Y114H) and Tyr116Ser (Y116S) variants formed more amyloid fibrils than the wild-type transthyretin, nonamyloidogenic Tyr116Val (Y116V) variant, and other amyloidogenic variants in previous studies. The secondary, tertiary, and quaternary structural stabilities of the Y114H and Y116S variants were compared with those of the wild-type transthyretin and nonamyloidogenic Y116V variant. The unfolding data indicated that the amyloidogenic Y114H and Y116S mutations reduced the stability of the secondary, tertiary, and quaternary structure. Our results also indicated that the unfolding of Y114H and Y116S is less cooperative than that of the wild-type transthyretin. Moreover, the tetramer of the amyloidogenic variants dissociated to the monomer even at pH 7.0, indicating the importance of Tyr114 and Tyr116 in strengthening the contacts between monomers and/or dimers of the transthyretin molecule.

Amino Acid Substitution↗
PubMed2003

Improved apparatus for solid-liquid multi-stage counter-current extraction.

An improved apparatus for solid-liquid multi-stage counter-current extraction (SLME) was developed. The apparatus has a set of 24 extraction vessels. Each extraction vessel unit is composed of a piston-cylinder in which the solid phase is placed, and a cup-cylinder in which the liquid phase is set. Of the 24 extraction vessels, 20 were used for the separation stage, and the other 4 were used for the back-extraction stage. (+/-)-Troger's base was selected as a racemic model compound for the continuous enantioseparation by the apparatus, and a cellulose derivative was used as the chiral separator. After 50 cycles of the operation (in 9 h), 0.1 g of (-)-enantiomer (85% in purity) was recovered from the solid phase by back-extraction with ethanol, whereas 1.1 g of (+)-isomer (75% in purity) was collected from the liquid phase (ethanol).

Chromatography, High Pressure Liquid↗
PubMed2003

[An autopsy case of cryptococcal meningoencephalitis: correlation of MRI and pathologic findings].

A comparative study of MRI and pathology was performed on a case of cryptococcal meningoencephalitis. An 11-year-old female presented with confusion and vomiting. On admission, CSF examination revealed spherical fungal cells with mild pleocytosis, decreased glucose and elevated protein level. MRI showed multiple punctate lesions in the basal ganglia with high intensity on T2-weighted image, while enhanced MRI revealed diffuse meningeal involvement. Post-mortem examination disclosed that the T2-weighted lesions found in the basal ganglia were aggregated small cystic lesions consisting of a cryptococcal invasion of Virchow-Robin spaces, termed "soap bubble lesions", characteristic findings of cryptococcal meningoencephalitis. Thus MRI findings of the basal ganglia and meninges may help to diagnose cryptococcal meningoencephalitis.

Brain↗
PubMed2003

[Long-term follow up of re-induction with a new synthetic retinoid, Am-80, for relapse of acute promyelocytic leukemia previously treated with all-trans retinoic acid: results of 7 cases from a single institute].

Seven patients experiencing first (n = 5) or second (n = 2) relapse of acute promyelocytic leukemia (APL) were treated with a new synthetic retinoid, Am-80. All 7 patients were previously treated with all-trans retinoic acid (ATRA). Am-80 was orally administered at a dose of 6 mg/m2 daily. Chemotherapy was combined in 3 patients because of leukocytosis. All 7 patients achieved a complete remission (CR) during periods ranging from 36-56 days (median 52 days). Adverse effects such as hyperlipidemia and skin lesions, were tolerable. After achieving CR, 3 patients underwent allogeneic bone marrow transplantation and 4 patients received only consolidation chemotherapy. In 2 of 3 patients who received allogeneic transplantation, relapse free survival has lasted for 9.7 and 28.3 months. Furthermore, in 2 of 4 patients who received only chemotherapy, relapse free survival has lasted for 84.7 and 90.1 months. Am-80 is an active agent for APL patients who have relapsed from ATRA-induced remission.

Adult↗
PubMed2002

M(3) receptor antagonism by the novel antimuscarinic agent solifenacin in the urinary bladder and salivary gland.

The antimuscarinic profile of the experimental drug solifenacin/YM905 [(+)-(1 S,3' R)-quinuclidin-3'-yl 1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate] for the treatment of overactive bladder was compared with the commonly prescribed agent oxybutynin. In radioligand binding assays, p K(i) values of solifenacin for M(1), M(2), and M(3) receptors were 7.6, 6.9, and 8.0, respectively. These values for oxybutynin were 8.6 (M(1)), 7.7 (M(2)), and 8.9 (M(3)). Solifenacin and oxybutynin antagonized the contractile effect of carbachol (CCh) on isolated guinea pig urinary bladder smooth muscle (detrusor), displaying the negative logarithm of antagonist apparent affinity constant (p K(b) value) of 7.1 for solifenacin and 7.4 for oxybutynin. To study the tissue selectivity between bladders and salivary glands, guinea pig detrusor and mouse submandibular gland cells were stimulated with CCh and monitored for intracellular Ca2+, as determined by Fura 2 fluorescence. Ca2+ mobilization of detrusor cells was inhibited equipotently by solifenacin (p K(i)=8.4) and oxybutynin (p K(i)=8.6), whereas that of the gland cells was antagonized less potently by solifenacin (p K(b)=7.4) than by oxybutynin (p K(b)=8.8), although the M(3) subtype mediated both cell responses. In anesthetized rats, solifenacin (63-2100 nmol kg(-1) or 0.03-1 mg kg(-1)) dose-dependently inhibited CCh-stimulated increases in urinary bladder pressure, while its inhibitory effects on salivation and bradycardia were apparent only at a dose of 2100 nmol kg(-1). In contrast, oxybutynin within a dose range of 77-770 nmol kg(-1) (0.03-0.3 mg kg(-1)) inhibited responses of the bladder and salivary gland slightly more potently than that of the heart. In addition, inhibitory effects of darifenacin indicated a major role of M(3) receptors in the bladder and salivary gland. Therefore, M(3) receptor antagonism by solifenacin could be bladder-selective. This selectivity remains to be elucidated and may provide new approaches to the pharmacotherapy of overactive bladder.

Animals↗
PubMed2002

Molecular cloning and characterization of chick sialoprotein associated with cones and rods, a developmentally regulated glycoprotein of interphotoreceptor matrix.

MY-174 is an IgM class monoclonal antibody originally established against chick PG-M/versican. The antibody specifically stains the photoreceptor layer, where we recently reported an absence of PG-M/versican. In this study, we re-characterized the antibody and identified the molecule that reacts to MY-174 at the photoreceptor layer. Immunohistochemistry localized the antigen to the matrix surrounding photoreceptors. A variety of glycosidase digestions showed that the antigen is the 150-kDa glycoprotein that has sialylated N- and O-linked glycoconjugates having a molecular mass of more than 30-kDa. The peptide sequences obtained from purified MY-174 antigen showed we had sequenced a full-length cDNA with an open reading frame of 2787 base pairs, encoding a polypeptide of 928 amino acids, with 56 and 54% identities to human and mouse sialoprotein associated with cones and rods (SPACRs), respectively, and with the structural features observed in SPACRs. The specific sialylated O-glycoconjugates here are involved in the epitope structure for MY-174. SPACR first appeared by embryonic days 15-16, and expression increased with developmental age, paralleling the adhesion between neural retina and retinal pigment epithelium. Thus, we concluded that the MY-174 antigen at the photoreceptor layer, a developmentally regulated glycoprotein, is identical to chick SPACR and may be involved in a novel system mediating adhesion between neural retina and retinal pigment epithelium.

Amino Acid Sequence↗
PubMed2002

Spongistatin synthetic studies. An efficient, second-generation construction of an advanced ABCD intermediate.

[reaction: see text] A short, efficient, and stereocontrolled synthesis of (-)-4, an advanced ABCD subunit of the spongistatins, has been achieved. Central to the synthetic strategy is the multicomponent linchpin union of silyl dithianes with epoxides to access both the AB and CD fragments. Fragment coupling was then achieved via an efficient stereoselective aldol reaction. The linear sequence required 22 steps and proceeded in 4.0% overall yield.

Animals↗
PubMed2002

Detection of cytomegalovirus DNA in human placenta.

Although human cytomegalovirus (CMV) is one of the most common causes of viral intrauterine and perinatal infection, its distribution in the placenta is poorly understood. The purpose of this study was to determine the frequency of CMV DNA positivity in placentas, to demonstrate the localization of the viral genome, and to identify the clinical features related to placental CMV. A total of 254 placentas from 231 mothers were investigated, and the maternal serum CMV immunoglobulin antibodies were measured. Specimens from both the placental parenchyma and the placental membrane close to the ruptured site in each placenta were examined for the presence of CMV DNA using dot blot hybridization after PCR amplification. None of 57 placentas from seronegative mothers was positive for CMV DNA. Of 197 placentas from seropositive mothers, 60 (30.5%) had CMV DNA in either the parenchyma or the membrane by dot blot analysis. In situ hybridization was carried out on these 60 placentas, and the localization of the viral genome was established in 19; CMV DNA was localized mostly to the villi, including the mesenchyme and trophoblasts, extravillous trophoblasts, and decidual cells. The mean gestational age at delivery was significantly later in the CMV DNA-positive placentas than in the negative placentas (36.9 +/- 5.1 vs 34.7 +/- 6.2 weeks, P = 0.0059). CMV DNA was detected in only 6 of 33 placentas delivered in the second trimester, and all six were associated with either severe maternal nephritis or severe chorioamnionitis. These results suggest that the CMV genome is common in placentas at later gestational ages and in those of earlier gestational ages with certain maternal complications.

Antibodies, Viral↗
PubMed2002

Establishment of novel B-cell precursor leukemia sister cell lines NALM-36 and NALM-37: shift of immunoglobulin phenotype to double light chain positive B-cell.

Two novel B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) sister cell lines, designated NALM-36 and NALM-37, were established from the peripheral blood (at diagnosis) and bone marrow (at relapse) of a 37-year-old woman with ALL. Immunophenotyping showed BCP type III pre-B cell characteristics including TdT, CD10, CD19, CD22, CD79a and HLA class II. T cell and myeloid-associated antigens tested were negative except CD5 which was 100% positive for both cell lines. The surrogate light chains lambda5 and VpreB were positive for both cell lines. Cytogenetic analysis of NALM-36 revealed an abnormal karyotype with 46, XX, add(1)(q?42), -14, +mar. Southern blot analysis of the immunoglobulin (Ig) genes status of NALM-36 at 10 months after establishment showed germ line configuration of the kappa light chain gene, and rearrangement of the lambda light and mu heavy chain genes. At 16 months we detected a phenotypic shift of Ig chain protein expression from a BCP-III pre-B cell phenotype to a BCP-IV mature B cell phenotype, with kappa and lambda double Ig light chain and mu heavy chain expression, both on the cell surface and in the cytoplasm. We designated this subline as NALM-36KL. Authenticity of the NALM-36KL, NALM-36 and NALM-37 cell lines was demonstrated by DNA fingerprinting. The extensive characterization of the sister cell lines suggests that these three novel cell lines, derived from a single patient, may represent unique and relevant in vitro model systems for BCP-type leukemia cells. They may provide useful models and unprecedented opportunities for analyzing the multitude of biological aspects of normal and neoplastic B-lymphocytes and their precursors.

Adult↗
PubMed2002

Establishment of the T-cell large granular lymphocyte leukemia cell line MOTN-1 carrying natural killer-cell antigens.

A novel interleukin-2 (IL-2) dependent leukemia cell line MOTN-1 was established from the peripheral blood of a 63-year-old woman with T-cell large granular lymphocyte (LGL) leukemia in chronic phase. Primary peripheral blood leukemia cells were CD3+, CD5+, CD7+, CD56+, CD94+, CD161+, TcRalphabeta+, and HLA-DR+. The immunoprofile of the established cell line MOTN-1, however, showed CD3-, CD5-, CD7+, CD56+, CD94+, CD159+, CD161+, TcRalphabeta- and HLA-DR+; the MOTN-1 cells were cytoplasmatically positive for CD3varepsilon and the products of the T-cell receptor (TcR) genes beta and gamma. While the TcRbeta and TcRgamma genes were rearranged, the TcRdelta gene was found to be deleted. DNA fingerprinting and chromosome analysis identifying the t(2;6)(q?23;q?21) and t(12;18)(q13;q?22) alterations demonstrated the authenticity and the malignant nature of the cell line. The scientific significance of MOTN-1 lies in (1) the rarity of this type of leukemia cell lines, (2) the co-expression of various T- and natural killer (NK)-cell-associated markers, and (3) its unique chromosomal aberrations.

Antigens, CD↗
PubMed2002

Can t(8;21) oligoblastic leukemia be called a myelodysplastic syndrome?

The new World Health Organization (WHO) classification of hematologic malignancies has incorporated t(8;21) myelodysplastic syndromes (MDS) according to the French-American-British classification into the category of acute myeloid leukemia (AML) with t(8;21)(q22;q22), while our knowledge about clinicopathological features of t(8;21) oligoblastic leukemia is still limited. We present our experience with 12 patients meeting the FAB diagnostic criteria of MDS and having t(8;21), who were compared to 43 t(8;21) AML patients. The MDS and AML patients shared most hematomorphologic, immunophenotypic, and clinical features, whereas the differences lay along myeloid maturation. The MDS patients had higher percentages of circulating neutrophils and marrow myeloid cells beyond promyelocytes than the AML patients. The incidence of Auer rods in mature neutrophils in MDS was significantly higher than that in AML, and furthermore, the neutrophils in MDS more commonly contain t(8;21) than in AML. Our findings support the rationale for the WHO classification, and future studies on large patient populations should help clarify whether the spontaneous differentiation potential could be actively associated with a hematological manifestation of t(8;21) leukemias.

Adult↗
PubMed2002

A novel L3-acute lymphoblastic leukemia cell line (BALM-27) carrying cytoplasmic immunoglobulin 8 chain but lacking expression of cell surface immunoglobulin chains.

A human acute lymphoblastic leukemia (ALL) cell line, BALM-27, was established from the peripheral blood specimen of a patient with B-cell ALL L3 type (ALL-L3) at diagnosis. As with the original leukemia cells, the established line was negative for all cell surface immunoglobulin (Ig) chains, but carrying only cytoplasmic Ig delta heavy chain. Southern blot analysis of the various Ig chain genes demonstrated homozygous deletion of the Jkappa gene, germ line configuration of the Jlambda and rearrangement of IgJH genes. Cytogenetic analysis of both primary leukemic bone marrow and BALM-27 cells showed the der(8;15)(q10;q10) chromosomal alteration, in addition to the t(8;22)(q24;q11) abnormality which is highly associated with ALL-L3 and Burkitt's lymphoma. The established cell line BALM-27 represents a rich resource of abundant, accessible, and manipulable cell material for analyzing the unique expression of Ig chain and for investigating the pathogenesis of B-cell malignancy. The scientific significance of BALM-27 lies in (1) the rarity of this type of leukemia cell lines, and (2) its unique chromosomal aberrations.

Aged↗
PubMed2002

Identification of an endo-beta-N-acetylglucosaminidase gene in Caenorhabditis elegans and its expression in Escherichia coli.

We report the identification, molecular cloning, and characterization of an endo-beta-N-acetylglucosaminidase from the nematode Caenorhabditis elegans. A search of the C. elegans genome database revealed the existence of a gene exhibiting 34% identity to Mucor hiemalis (a fungus) endo-beta-N-acetylglucosaminidase (Endo-M). Actually, the C. elegans extract contained endo-beta-N-acetylglucosaminidase activity. The putative cDNA for the C. elegans endo-beta-N-acetylglucosaminidase (Endo-CE) was amplified by polymerase chain reaction from the Uni-ZAP XR library, cloned, and sequenced. The recombinant Endo-CE expressed in Escherichia coli exhibited substrate specificity mainly for high-mannose type oligosaccharides. Man(8)GlcNAc(2) was the best substrate for Endo-CE, and Man(3)GlcNAc(2) was also hydrolyzed. Biantennary complex type oligosaccharides were poor substrates, and triantennary complex substrates were not hydrolyzed. Its substrate specificity was similar to those of Endo-M and endo-beta-N-acetylglucosaminidase from hen oviduct. Endo-CE was confirmed to exhibit transglycosylation activity, as seen for some microbial endo-beta-N-acetylglucosaminidases. This is the first report of the molecular cloning of an endo-beta-N-acetylglucosaminidase gene from a multicellular organism, which shows the possibility of using this well-characterized nematode as a model system for elucidating the role of this enzyme.

Acetylglucosaminidase↗