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Biomedical subjects

H Hamazaki

Publications and source records attributed to H Hamazaki.

At least 19 recordsLinked to original sources

[Clinical evaluation of cefpirome sulfate for severe infections in patients with hematological disorders. Hanshin Study Group of Hematopoietic Disorders and Infections].

We investigated the therapeutic efficacy and safety of cefpirome sulfate (CPR) in treatment of hematopoietic disorder-associated infections. A total of 219 patients were admitted to 12 hospitals of Hanshin Study Group of hematopoietic disorders and infections between April 1994 and March 1996 and were enrolled in this study. Most patients received intravenously infused CPR at a dose of 1 or 2 g twice a day for 3 days or more. Twenty nine patients dropped out or were excluded and remaining 190 patients were adopted for the evaluation. A overall response rate was 58.4% (111/190). Among neutropenic patients, the response rate was 50% (8/16) in patients whose peripheral neutrophil counts (PNC) remained less than 100/microliter throughout the observation period and was 53.7% (22/41) in patients with PNC remained less than 500/microliter. In contrast, in patient whose PNC was below 500 before the treatment but exceeded 501/microliter during of at the end of the treatment, the response rate was as high as 78.4% (29/37). When G-CSF was combined, the response rate became significantly (P < 0.05) higher, 68.5% (50/73), as compared with that, 52.1% (61/117), in patients without it. In cases in which the causative organisms could be identified, the organisms were eliminated in 81.8% (9/11) of the patients infected with Gram-positive bacteria, whereas in 100% (12/12) in those infected with Gram-negative bacteria. Skin eruption developed in 6 patients during the treatment with CPR, and vascular pain and parosmia in one each other. These symptoms subsided soon after discontinuation or even without discontinuation of CPR. Abnormal laboratory findings, mainly liver dysfunction, i.e. elevation of slight degree of serum transaminase levels, were observed. The values, however, turned to normal immediately after the cessation or completion of the treatment. In conclusion, CPR is considered to be an antibiotic of value with high efficacy and safety in treatment of hematopoietic disorder-associated infections.

Adolescent

A beta-amyloid peptide variant related with familial Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis is poorly eliminated by cathepsin D.

The cerebral deposition of 40-42 residue amyloid beta-protein (Abeta) is a characteristic of Alzheimer's disease. Cathepsin D is possibly involved in the intracellular clearance of Abeta (Hamazaki, H. (1996) FEBS Lett., in press). The present work shows that cathepsin D hydrolyzes wild-type Abeta 20 times faster than a variant Abeta with a substitution at residue 21 from Ala to Gly. Since the substitution has been linked to familial Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis (Hendriks et al. (1992) Nature Genet. 1, 218-221), the present observations suggest that the inefficient elimination of Abeta by cathepsin D is capable of being one of causes of the amyloid fibril formation.

Alzheimer Disease

Cathepsin D is involved in the clearance of Alzheimer's beta-amyloid protein.

The cerebral deposition of 39-42 residue amyloid beta-protein (Abeta) is a histopathological characteristic of Alzheimer's disease. The present study is aimed at finding proteinases responsible for the intracellular clearance of Abeta. The Abeta-degrading proteinase was purified from rat brain. Amino-terminal sequence analysis indicated the Abeta-degrading proteinase was cathepsin D. Purified cathepsin D hydrolyzed Abeta between Phe19 and Phe20. Cathepsin D is likely to be involved in the intracellular clearance of aggregatable Abeta, since Abeta fragments with Phe20 at the amino-terminus have been reported to be secreted from several lines of cultured cells.

Amino Acid Sequence

Amyloid P component promotes aggregation of Alzheimer's beta-amyloid peptide.

Amyloid P component (AP) has been recognized as a beta-amyloid-associated protein but the pathological role is not known. In the present experiments, it has been shown that AP promotes the aggregation of Alzheimer's beta-amyloid peptide (A beta) in the presence of a physiological concentration of Ca2+. The aggregation promotion was observed at a concentration of soluble A beta 1-40 in human cerebrospinal fluid. The results suggest that AP is possibly a pathogenic factor of the cerebral amyloidosis.

Amyloid beta-Protein Precursor

Ca(2+)-dependent binding of human serum amyloid P component to Alzheimer's beta-amyloid peptide.

Serum amyloid P component (SAP), a normal glycoprotein, is universally found in amyloid deposits, including cerebrovascular amyloid of Alzheimer's disease. This paper describes the Ca(2+)-dependent binding of human SAP to Alzheimer's beta-amyloid peptide (A beta). 125I-SAP binds to synthetic human A beta-(1-40) immobilized on microtiter plates at a dissociation constant of 6.0 x 10(-9) M in 0.01 M Tris-HCl, 0.15 M NaCl, pH 7.5, containing 2 mM Ca2+, 1% bovine serum albumin, and 0.05% Tween 20. Binding inhibition assay has shown that soluble A beta-(1-40) and A beta-(1-28) also bind to SAP. Since SAP is resistant to proteases in the presence of calcium, the Ca(2+)-dependent binding of SAP to soluble A beta and to beta-amyloid fibrils would give pathological effects on fibril formation and persistence of beta-amyloid in Alzheimer's disease.

Amyloid beta-Peptides

Human serum amyloid P component binds to a specific peptide in the presence of calcium.

Human serum amyloid P component (SAP) binds to a carboxyl-terminal peptide of residues 160-204 of SAP itself in the presence of calcium. A set of sequentially overlapping decapeptides covering the entire length of residues 160-204 of SAP was synthesized on polyethylene pins to be used for binding assay, and six overlapping peptides in residues 190-204 (Tyr-Glu-Ile-Arg-Gly-Tyr-Val-Ile-Ile-Lys-Pro-Leu-Val-Trp-Val) were found to have equally high affinity for SAP. The validity of using peptides on polyethylene pins was shown by the binding assay using 11-residue soluble peptide corresponding to residues 194-204. Replacement of the Lys or the Ile residues with Glu abolished the binding activity.

Amino Acid Sequence

Possible involvement of protein kinase C activation in down-regulation of CD3 antigen on adult T cell leukaemia cells.

The role of protein kinase C (PKC) system on CD3 expression on adult T-cell leukaemia (ATL) was examined. The down-regulation of CD3 on ATL cells is reportedly induced by CD3 down-regulating factor (CD3DF) contained in serum and culture supernatants of leukaemia cells from acute type ATL patients. After we cultured normal PBMC with a PKC inhibitor, H-7, CD3DF activity for PBMC was reduced significantly. Culture with H-7 of HTLV-1 transformed T cells, ATL-2 cells whose CD3 expression had been decreased, led to enhancement of CD3 expression in a time-dependent manner. These findings suggest that CD3DF may play an important role as a PKC system activator, resulting in CD3 down-regulation.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

Detection of minimal residual disease using clonospecific primers for CDRIII in patients with acute B lymphocytic leukemia with or without Philadelphia chromosome: possibility of clinical application as a tool for improving prognosis.

We attempted to identify the minimal residual leukemic clone as related to the clinical course in patients with acute B lymphocytic leukemia (B-ALL). DNA was extracted from stored bone marrow slides, and the third complementarity determining region (CDRIII) was amplified by polymerase chain reaction (PCR) using primers with consensus sequences for VH and JH. After amplification of the CDRIII band, the DNA fragment of CDRIII was inserted into the cloning vector PUC118. After cloning, the DNA sequences for CDRIII were determined. Clonospecific DNA sequences in CDRIII were selected, and clonospecific primers for each patient were synthesized. Using the clonospecific primers, we carried out second-round PCR to detect minimal residual disease (MRD) during several stages of the clinical course. Basically, the sensitivity of detection for MRD was between 10(-4) and 10(-5) cells. Even when leukemic cells were not detected in the morphologic study, with this detection system, the MRD was identified as an amplified CDRIII band stained with ethidium bromide on agarose gel. After bone marrow transplantation (BMT), MRD was detected for at least 4 months. In this article, we discuss the difference in sensitivity of detection for MRD between the BCR-ABL fusion gene and CDRIII in Philadelphia chromosome-positive (Ph+) B-ALL, as well as the possible clinical application of this method to predict relapse and prognosis.

Adolescent

[Clinical efficacy of arbekacin on MRSA infections with hematopoietic disorders. The Hanshin Study Group of Hematopoietic Disorders and Infections].

Arbekacin (ABK) was administered to 17 patients with MRSA infections that complicated underlying hematopoietic disorders, and the efficacy and safety were evaluated. The underlying diseases included acute myelocytic leukemia (8 cases), acute lymphocytic leukemia (1) myelodysplastic syndrome (3), chronic myelocytic leukemia (1), non-Hodgkin's lymphoma (2), Hodgkin's disease (1) and adult T cell leukemia (1). The infections consisted of septicemia (5 cases), pneumonia (4), upper respiratory tract infections (6) and urinary tract infections (2). ABK was administered by i.v. drip infusion in daily doses of 150-200 mg, given in two divided dosages. The therapeutic efficacies were: excellent in 2 (2 septicemias), good in 7 (1 septicemia, 4 upper respiratory infections, 2 urinary tract infections), fair in 2 (septicemia and pneumonia) and poor in 6 (1 septicemia, 3 pneumonias, 2 upper respiratory infections). As a side effect, reversible renal dysfunction was detected in four cases. Causative bacteria were isolated from six cases. They were all coagulase type II and MIC's of ABK were from 0.25 microgram/ml to 4.0 micrograms/ml. Arbekacin therapy was found to be effective even in patients with hematopoietic disorders accompanied by MRSA infections.

Adolescent

CD3 down-regulating factor in sera and culture supernatants of leukaemic cells from patients with adult T cell leukaemia.

Immunological abnormality of T lymphocytes in patients with adult T cell leukemia (ATL) is characterized by abnormal expression of the 55 kD chain of the receptor for interleukin 2 (IL-2R/p55) (Tac), and the down-regulation of CD3 expression. Using serum and culture supernatants of leukaemic cells from ATL patients (Group A) whose CD3 expression was down-regulated and those (Group B) whose CD3 was not low, the possible mechanism of CD3 down-regulation on ATL cells was discussed. When PBMC from normal individuals were cultured with sera from ATL patients for 24 h, CD3 expression revealed by mean fluorescent intensity (MFI) was down-regulated by sera from ATL patients in Group A (MFI: Pt 1 = 51.6 +/- 4.5, Pt 2 = 48.0 +/- 6.9, control = 96.5 +/- 6.6), not by sera from patients in Group B (MFI: Pt 3 = 105.5 +/- 7.9, Pt 4 = 102.5 +/- 8.3, control = 96.5 +/- 6.6). When normal PBMC were cultured with supernatants of leukaemic cells from ATL patients in Group A, this CD3 down-regulating activity was also detected (MFI: Pt 1 = 78.0 +/- 10.2, Pt 2 = 70.6 +/- 8.7, control = 94.0 +/- 6.6). By using gel-chromatography, the fractionated supernatants from ATL patients in Group A decreased CD3 expression of normal PBMC significantly (MFI: Pt = 22.9 +/- 5.8, Pt 2 = 28.8 +/- 7.4, control = 92.1 +/- 9.6). This CD3 down-regulating activity in fractionated supernatant was not inhibited by any lymphokine antibodies, anti-IL-1 alpha antibody (Ab), anti-IL-1B Ab, anti-IL-2 Ab, anti-IL-3 Ab, anti-IL-4 Ab, anti-IL-6 Ab, anti-TNF-alpha Ab and anti-IFN-gamma Ab. Any known cytokines (IL-1, IL-2, IL-3, IL-4, IL-6, TNF-alpha and IFN-gamma) could not modulate CD3 expression of normal PBMC. These findings suggested that there are novel factor(s) with CD3 down-regulating activity in the serum and culture supernatant of ATL patient and those factor(s) are involved in progression of ATL.

Adult

[Studies on pseudo-Chediak-Higashi granules formation in acute promyelocytic leukemia].

Leukemic cells from acute promyelocytic leukemia containing pseudo-Chediak-Higashi (P-CH) granules in a 38-year-woman were studied with ultrastructural and cytochemical techniques to evaluate the origin and nature of the granules. Wright-Giemsa stain revealed giant granules to be azurophilic. Cytochemical stain revealed p-CH granules ot the basic of their peroxidase and glycoprotein content. Electron microscopy revealed numerous giant granules formed by fusion of azurophilic granules these morphological, different type granules were classified into four types, 1) circular granule with homogeneous matrix, 2) circular granule with heterogeneous change by autolysis, 3) Auer body-like granule with crystalline arrangement, 4) vacuolar formation. The results demonstrate that the Auer body-like granule of P-CH granules in leukemic cells is a morphologically variant type of the classical Auer body observed in common acute myeloid leukemia.

Adult

Induction of anti-idiotypic T cells through a network mechanism.

BALB/c mouse T cells that recognized the idiotype expressed on M104E(mu, lambda 1) were induced by immunization with Dextran B-1355. T cells derived from mice immunized with 1 mg of Dextran B-1355 showed a marked proliferative response against M104E, whereas T cells from mice immunized with Ficoll or smaller amounts of Dextran B-1355 did not. BCL1Id, which had an identical isotype, did not induce proliferation of T cells. The T cell proliferative response against the idiotype on M104E required macrophages as antigen-presenting cells. The proliferative response was inhibited when antigen-presenting cells were treated with NH4Cl or chloroquine, which are antigen-processing inhibitors. These results indicate that anti-idiotypic T cells which recognized processed idiotopes could be induced physiologically through a network mechanism.

Animals

Structure and significance of N-linked sugar unit of human serum amyloid P component.

Human serum amyloid P component (SAP) was digested with pronase P and a glycopeptide fraction was obtained by gel-permeation chromatography. Carbohydrate and amino-acid composition of the glycopeptide suggested that each subunit of SAP possesses an N-linked glycan, but no O-linked ones. The N-linked oligosaccharide of SAP was obtained by hydrazynolysis. The structure of the oligosaccharide, which was deduced by sequential digestion with exoglycosidases and subsequent gel filtration, was identical or very similar to that of human transferrin. Removal of sialic acids from SAP reduced the calcium-dependent binding activity for agarose by 7%, suggesting the terminal sialic acids were partially responsible for the binding.

Amino Acids

Cardiac sports rehabilitation for patients with ischemic heart disease.

This paper summarizes data gathered from an 8 years sports cardiac rehabilitation program at Kyoto University and satellite hospital (Takeda Hospital). In total, 185 patients were rehabilitated under our original program with no serious cardiac accidents. Compliance was 58.2% after 6 months of this rehabilitation. In patients selected to evaluate the value of rehabilitation, exercise study with treadmill and 201Tl scintigraphic study showed improvement in exercise tolerance (in 58% of patients) and in perfusion on exercise (in 40%). Coronary angiographic study showed regression of arterial narrowing in 16% of the patients studied. We conclude that in addition to emotional and psychological support, our sports cardiac rehabilitation is safe and effective in improving exercise tolerance and cardiac perfusion.

Coronary Angiography

[Factors related to prognosis and relapse in acute myelomonocytic and monocytic leukemias (M4 and M5)].

To analyse the factors which were related to prognosis at first examination and early diagnosis of relapse in complete remission phase, 26 patients with acute myelomonocytic leukemia (M4) and acute monocytic leukemia (M5) were investigated. There was a tight relationship between age and remission rate in patients with M4 and M5. Six of M4 with eosinophilia (M4Eo) patients revealed 83.3% as remission rate with good prognosis in the survival curve. LDH level of them was lower than other patients significantly. In order to diagnose relapse before clinical manifestations, it was useful to follow up number of mature monocytes (over 600/microliters) in the peripheral blood.

Adolescent

Calcium-dependent polymerization of human serum amyloid P component is inhibited by heparin and dextran sulfate.

The calcium-dependent polymerization of human serum amyloid P component (SAP) was spectrophotometrically monitored in 0.15 M NaCl at pH 7.5. The rate of the polymerization depended on the concentrations of SAP and Ca2+. It was shown for the first time that the calcium-dependent polymerization of SAP was inhibited by some sulfated polysaccharides. Most potent inhibitors were heparin and high molecular weight dextran sulfate of Mr 1.0.10(6). The inhibitory activity of glycosaminoglycans is accordant to their binding affinity for SAP, which was reported previously (Hamazaki, H. (1987) J. Biol. Chem. 262, 1456-1460). The polymerized SAP was reversibly dissociated by heparin and high molecular weight dextran sulfate. The results suggest that heparin and high molecular weight dextran sulfate may be a useful dissociating agent of polymerized SAP in amyloid deposits.

Calcium