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Biomedical subjects

M Takeuchi

Publications and source records attributed to M Takeuchi.

At least 685 records · Page 38Linked to original sources

[Transmitral flow velocity patterns as influenced by preload, afterload and heart rate alterations: pulsed Doppler echocardiographic study].

The influences of preload, afterload and heart rate alterations on the pattern of left ventricular filling were investigated using pulsed Doppler echocardiography (PDE) in humans. Transmitral flow at the level of the valvular tip was recorded during dextran infusion, lower body negative pressure, angiotensin II infusion, and atrial and atrioventricular sequential pacings. Peak velocity of rapid filling (R), peak velocity of atrial contraction (A), the ratio of peak velocities (A/R), flow velocity integrals of the rapid filling phase (IR) and atrial contraction (IA) were obtained. PDE and the measurement of hemodynamics during lower body negative pressure (0, -10 mmHg, -20 mmHg) and dextran infusion (100 ml, 200 ml) were studied in 22 patients with ischemic heart disease. R decreased significantly after lower body negative pressure, and increased significantly during dextran infusion. Before and during angiotensin II infusion, PDE and the measurement of hemodynamics were studied in 14 patients with ischemic heart disease. The patients were categorized into 2 subgroups according to left ventricular function. During afterload stress, the A/R and IA increased in patients with normal left ventricular function; whereas, the A/R decreased in patients with poor left ventricular function. PDE was recorded during right atrial and atrioventricular sequential pacings at the heart rates of 60 to 100 beats/min in 29 patients with ischemic heart disease. When the heart rates increased, R decreased during atrial and atrioventricular sequential pacings. The A increased after the occurrence of the summation between the rapid and atrial filling waves. The A/R gradually increased with incremental heart rate. These results indicate that changes in the preload alter the peak velocity of left ventricular filling pattern of transmitral flow. The effects of the increasing afterload depend on the basal left ventricular function, with an increase in the peak velocity of atrial contraction being observed in the presence of normal left ventricular function. Both the peak velocity of rapid filling and atrial contraction were related to the heart rate and atrioventricular conduction delay. In assessing left ventricular filling dynamics using PDE, the influence of the preload, afterload and heart rate must be considered.

Angiotensin II↗

[An autopsy case of progressive supranuclear palsy with olivary hypertrophy].

Clinical and pathologic findings of an autopsy case of progressive supranuclear palsy (PSP) with a 7 year clinical course are described. The patient exhibited clinical findings of typical PSP, cerebellar signs and rhythmical myoclonus that was about 2 Hz and synchronous in the eyes, palate, and pharynx, which is so called palatal myoclonus. Pathological findings compatible with those in PSP i.e. loss of nerve cells, neurofibrillary tangles (NFT), and gliosis were found in the globus pallidum, thalamus, subthalamic nucleus, substantia nigra, locus coeruleus, nucleus of Raphe, reticular formation, dentate nucleus, and inferior olives. Nerve cells in the nucleus basalis were preserved. Distinctive findings included marked degeneration of the dentate nucleus, prominent hypertrophy of the inferior olives, and atrophy and subcortical gliosis of the frontal lobe. Hypertrophy of the inferior olives and palatal myoclonus represent an unusual PSP. It is presumed hypoxic injury unmasked the palatal myoclonus in this setting of dentate nucleus and inferior olivary complex degeneration.

Aged↗

[A case of Behçet's disease associated with myopathy during cyclosporin treatment].

A 46-year-old male was admitted to the Department of Neurology complaining of gait disturbance. He was given a diagnosis of Behçet's disease and placed on colchicine (0.5-1.0 mg/day) for 7 months without improvement. Subsequently cyclosporin (290 mg/day) was added this regimen. However, 7 months after initiation of combined colchicine/cyclosporin therapy serum creatine kinase (CK) rose to 1,255 U/l. On admission, neurological examination revealed generalized muscle atrophy with predominant proximal muscle weakness and decreased deep tendon reflexes. No myalgia was noted. Laboratory tests demonstrated anemia, liver dysfunction, chronic renal failure and an elevated serum CK level. The plasma cyclosporin concentration was 220 ng/dl, which is within therapeutic limits. Motor unit potentials in electromyography of bilateral quadriceps muscles were generally of short duration and reduced amplitude. A biopsy of quadriceps muscle showed variability in the size of type 2 fibers and scattered small vacuoles. Some of the vacuoles resembled rimmed vacuoles. These vacuoles were stained positively for acid phosphatase. Electronmicroscopy revealed that these vacuoles contained dense bodies, myeloid bodies, and glycogen particles. Collectively suggesting that these structures are autophagic vacuoles. Cyclosporin was reduced to 200 mg/day with unchanged colchicine dose and bromocriptine, which potentiates cyclosporin effects, was started. Gradual recovery from muscle weakness ensued. These findings suggest that cyclosporin contributed to the pathogenesis of this myopathy. On increase in use of cyclosporin, one should consider the possibility of myopathy as one of its side effects especially in combination therapy with myotoxic drugs such as colchicine.

Behcet Syndrome↗

Determination of octopine by pre-column fluorescence derivatization using benzoin.

A sensitive fluorimetric method for the determination of octopine, a member of opine family, is presented. The method is based on the formation of a fluorescent derivative of octopine with benzoin and the separation by high performance liquid chromatography using a reversed-phase column (Kaseisorb LC ODS-300) within 20 min. The octopine derivative is completely separated from other guanidino compounds including arginine which is generally very high in marine invertebrates. This method gives higher sensitivity, 5 pmol minimum detection, and better reproducibility than the electrophoresis method and colorimetric method.

Animals↗

Role of sugar chains in the in vitro biological activity of human erythropoietin produced in recombinant Chinese hamster ovary cells.

Human erythropoietin contains three Asn-type and one mucin-type sugar chains. That the branching structure of the outer portion of Asn-type sugar chains is correlated to its biological activity in vivo has been reported recently (Takeuchi, M., Inoue, N., Strickland, T. W., Kubota, M., Wada, M., Shimizu, R., Hoshi, S., Kozutsumi, H., Takasaki, S., and Kobata, A. (1989) Proc. Natl. Acad. Sci. U. S. A. 86, 7819-7822). In this study, the effect of trimming of sugar chains on the biological activity in vitro of this hormone was examined by using several glycosidases. Human erythropoietin produced by recombinant Chinese hamster ovary cells showed three times higher activity after desialylation. The activity was not changed significantly by further removal of the mucin-type sugar chain from the hormone, indicating no contribution of this type of sugar chain to the activity of erythropoietin in vitro. Sequential removal of galactose and N-acetylglucosamine from the outer chain moieties of the desialylated Asn-type sugar chains raised the activity of the hormone up to four and five times the intact erythropoietin, respectively. The activation effect was diminished slightly by further removing alpha-mannosyl residues and to a great extent by removing beta-mannosyl residues from the core portions of the Asn-type sugar chains. N-Glycanase digestion of intact erythropoietin resulted in almost complete loss of the activity in vitro. These results indicate that the core portion of the Asn-type sugar chains is necessary for erythropoietin to express its full biological activity in vitro and suggest that removal of the core portion of the sugar chains destroys the active conformation of erythropoietin.

Animals↗

Production of active and passive anaphylactic shock in the WBB6F1 mouse, a mast cell-deficient strain.

The role of mast cells in active and passive anaphylactic shock was examined using the WBB6F1 mouse, a genetically mast cell-deficient strain. Lethal anaphylactic shock occurred at high incidence rates in mice actively sensitized to bovine serum albumin (BSA). The reaction was specific to BSA since the shock could not be elicited by human or guinea pig serum albumin in these animals. Lethal shock could be prevented by CV-3988 but not by cyproheptadine, which suggests that the shock is mediated by PAF but not by histamine and serotonin. Similarly, lethal shock was provoked by homologous antigens in mice which had been passively sensitized with allogeneic anti-benzylpenicilloyl (BPO) IgG1 monoclonal antibody or with allogeneic or xenogeneic anti-BSA antiserum, but not in those sensitized with allogeneic anti-BPO IgE monoclonal antibody. These findings suggest that mast cells are not necessarily required for anaphylactic shock in the mouse.

Anaphylaxis↗

Chemical modification of erythropoietin: an increase in in vitro activity by guanidination.

Human recombinant erythropoietin (rHuEPO) was chemically modified with several group-specific reagents in order to study the role of each kind of amino-acid residue in its biological activity. Guanidination of the amino groups of the lysine residues yielded derivatives that showed higher activities in vitro than native rHuEPO, whereas amidination had no effect on the activity. By contrast, modification of the positive charges of the lysine residues to neutral or negative charges, such as in carbamylation, trinitrophenylation, acetylation or succinylation, caused a significant loss of rHuEPO activity. Chemical modification of other amino-acid residues, such as arginine and tyrosine residues or carboxyl groups, also led to loss of activity.

Arginine↗

Flow cytometric evaluation of Thomsen-Friedenreich antigen on transitional cell cancer using monoclonal antibody.

In 31 transitional cell cancer (TCC) tissues and 5 normal bladder mucosae (NBM), we compared the results of flow cytometry (FCM) and immunohistochemical examination in evaluating the expression of Thomsen-Friedenreich antigen (T-Ag) using a monoclonal antibody. On immunohistochemical examination, 14 (45%) cancer tissues showed T-Ag, while 7 (23%) cancer tissues and all NBM showed only cryptic T-Ag, which was detected only after neuraminidase treatment. Ten (32%) high grade cancer tissues showed neither T-Ag nor cryptic T-Ag. ON FCM the T-Ag positive cells (TPC) and the T-Ag positive cells after neuraminidase treatment (nTPC) were counted in fresh cell suspensions. FCM was more sensitive than immunohistochemical study in detecting T-Ag. Additionally, FCM revealed that some tumors had both T-Ag and cryptic T-Ag at the same time. The ratio of nTPC to TPC was well correlated with the stage or grade of the tumor and may be a more reliable marker of TCC than the expression of T-Ag assessed by immunohistochemical techniques.

Antibodies, Monoclonal↗

Successful treatment for perinephric abscess with recombinant human granulocyte colony-stimulating factor following nephrectomy in a patient of myelodysplastic syndrome: a case report.

The 35-year-old man with myelodysplastic syndrome (MDS) and granulocytopenia with dry cough and high fever was eventually found to have a left perinephric abscess of Staphylococcus aureus. He underwent left nephrectomy and drainage of perinephric space in conjunction with appropriate antibiotics. However, because of persistent granulocytopenia, Staph. aureus never cleared up with formation of only poor granulation. Recombinant human granulocyte colony-stimulating factor (G-CSF) was added to the above treatment leading to prompt improvement in granulocytopenia and emergence of the good granulation tissue. G-CSF will probably become one of the important agents in treating MDS with granulocytopenia.

Abscess↗

Effects of prolonged exposure to interferon-alpha on the viability, proliferation, differentiation, and tumorigenicity of HL-60 promyelocytic leukemia cells.

HL-60 promyelocytic leukemia cells were cultured continuously in the presence of 22,000 IU/ml of purified interferon-alpha (IFN-alpha) for up to 469 days. Study of the properties of the cells at various times during this period showed some changes in their expression of IgG Fc receptors, and in the maturation of the cells as indicated by their esterase content. The differences from control cells cultured in parallel were most marked after exposure to IFN-alpha for some 40-300 days, but were no longer seen after 400-470 days. The difference in tumorigenicity was significant after 150 days, but no longer after 300 days.

Animals↗

Inhibitory effect of pseudo-aminosugars on oligosaccharide glucosidases I and II and on lysosomal alpha-glucosidase from rat liver.

We examined the inhibitory effect of three pseudo-aminosugars (validamine, valienamine, and valiolamine), which were isolated from the broth of Streptomyces hygroscopicus, on the oligosaccharide-processing glucosidases I and II involved in glycoprotein biosynthesis in rat liver. Both glucosidases I and II were inhibited to the same extent by the pseudoaminosugars, and valiolamine had a more potent inhibitory activity than validamine or valienamine. A 50% inhibition of valiolamine was observed at 12 microM for glucosidase I and glucosidase II activities acting respectively on the substrates Glc3Man9GlcNAc2 and p-nitrophenyl alpha-D-glucopyranoside. Further, in order to investigate further the ability of valiolamine to inhibit glucosidase I, reaction products were analyzed by gel filtration on a Bio-Gel P-4 column. We also compared the inhibitory action of these pseudo-aminosugars on the acid alpha-glucosidase of rat liver lysosomes. They competitively inhibited the hydrolysis of both substrates, maltose and glycogen. Valiolamine again had a more potent lysosomal alpha-glucosidase inhibitory activity than the other two. The Ki values of valiolamine for the hydrolysis of maltose and glycogen were 8.1 and 11 microM, respectively. Valiolamine is a particularly effective inhibitor of oligosaccharide glucosidases I and II and of lysosomal alpha-glucosidase. Hence valiolamine might be useful as a research tool in investigations of carbohydrate metabolism.

Amino Sugars↗

Purification and characterization of a cysteine endopeptidase in cotyledons of germinated mung bean seeds.

A cysteine endopeptidase (EC 3.4.22.-) present in cotyledons of mung bean (Vigna radiata) seedlings was purified to homogeneity, as judged by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). This proteinase has an apparent molecular mass of 33 kilodaltons as estimated by SDS-PAGE and belongs to the class of cysteine proteinases as judged by the effects of various proteinase inhibitors on the activity of the enzyme. When proangiotensin is used as a substrate, the enzyme preferentially hydrolyzes the peptide bonds formed by the amino group of Leu or lle in this oligopeptide chain; for the enzyme to cleave those bonds, peptide sequences consisting of at least three amino acid residues on the amino side of Leu or lle must be present. The proteinase readily digests globulin present in mung bean cotyledons to smaller polypeptides.

Journal Article↗

In vitro production of B cell growth factor and B cell differentiation factor by peripheral blood mononuclear cells and bronchoalveolar lavage T lymphocytes from patients with idiopathic pulmonary fibrosis.

The activation of B lymphocytes and formation of immune complexes have been suggested to play an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). To investigate the mechanisms of activation of B lymphocytes, we studied the production of B cell growth factor (BCGF) and B cell differentiation factor (BCDF) in patients with IPF and those with interstitial pneumonia associated with collagen vascular diseases (IP-CVD), in comparison with healthy controls. Culture supernatants of peripheral blood mononuclear cells from patients with IPF induced more IgM and IgA production by B lymphocytes than those from healthy controls, indicating a higher production of BCDF in the patients. Culture supernatants of T lymphocytes obtained from bronchoalveolar lavage fluids (BALF) of patients with IPF induced higher proliferation of B lymphocytes than those from healthy controls, indicating a higher production of BCGF. An increase in production of BCGF and BCDF was not observed in patients with IP-CVD. In the light of these results, it was suggested that there may be an imbalance in T lymphocyte subsets that release lymphokines like BCGF and BCDF in patients with IPF, and that the subsets may differ between blood and BALF. It remains to be elucidated whether the activation of B lymphocytes depending on T lymphocytes determines the development of disease in IPF.

Adult↗

Immunohistochemical analysis of effects of cyclosporin A on gingival epithelium.

Cyclosporin A (CSA)-induced gingival overgrowth was immunohistochemically compared with that phenytoin-induced and nonspecific inflammatory gingiva, and CSA concentration was determined for dental plaque. Leu-6+ epithelial dendric cells (EDC) were found to significantly decrease in number in CSA-induced gingival overgrowth, while the ratio of HLA-DR+ EDC to Leu-6+ EDC did not change significantly. The expression of class II major histocompatibility complex antigens, such as HLA-DR, -DP and -DQ on keratinocytes did not change by CSA-treatment. Leu-4+ mononuclear cells in CSA-induced gingival overgrowth were located primarily in the connective tissue far outside the epithelium. CSA concentration was much higher in dental plaque than in blood and other tissues. Immune response thus appears to be suppressed in the epithelial layer of CSA-induced gingival overgrowth through decrease in Leu-6+ HLA-DR+ EDC and T cell infiltration, both due to CSA in dental plaque. DNA polymerase alpha was detected in much fewer basal keratinocytes of CSA- and phenytoin-induced gingival overgrowth. Epithelial hyperplasia may thus be not due to increased keratinocyte proliferation, but rather to enhanced keratinocyte life span.

Adolescent↗

Chemical modification by 2,4,6-trinitrobenzenesulfonic acid (TNBS) of an essential amino group in 3-ketovalidoxylamine A C-N lyase.

3-Ketovalidoxylamine A C-N lyase of Flavobacterium saccharophilum is a monomeric protein with a molecular weight of 36000, and contains 32 amino groups and no cysteine or cystine residues. The enzyme was inactivated by 2,4,6-trinitrobenzenesulfonic acid (TNBS) following pseudo-first order kinetics. Substrate of the lyase, p-nitrophenyl-3-ketovalidamine, protected the enzyme against the inactivation, suggesting that the modification occurred at or near the active site. Although several amino groups were modified by TNBS, a plot of log (reciprocal of the half-time of inactivation) versus log (concentration of TNBS) suggested that one amino group has an essential role in catalysis.

Amino Acids↗