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Biomedical subjects

M Yamasaki

Publications and source records attributed to M Yamasaki.

At least 37 records · Page 2Linked to original sources
PubMed2004

Acceleration of superoxide generation in polymorphonuclear leukocytes and inhibition of platelet aggregation by alk(en)yl thiosulfates derived from onion and garlic in dogs and humans.

We recently identified sodium n-propyl thiosulfate (NPTS) and sodium 2-propenyl thiosulfate (2PTS) from boiled onion and garlic, respectively, as causative agents of hemolytic anemia in dogs. We present here data concerning the effects of these alk(en)yl thiosulfates on superoxide (O(2)(-)) generation in peripheral polymorphonuclear leukocytes (PMNs) and on adenosine 5'-diphosphate (ADP)-induced platelet aggregation in dogs and humans in vitro. Both NPTS and 2PTS increased O(2)(-) generation significantly (P<0.05 at 1mM NPTS, P<0.005 at 0.1 and 1mM 2PTS) and reduced its reaction time significantly (P<0.05 between 0.01 and 1mM NPTS and at 1mM 2PTS) in canine PMNs stimulated by phorbol 12-myristate 13-acetate, compared with the control without alk(en)yl thiosulfates. However, a tendency to return to the control level was observed at 10mM of the alk(en)yl thiosulfates in both O(2)(-) generation and its reaction time. Although NPTS and 2PTS did not exert any significant effect on the O(2)(-) generation in human PMNs, 2PTS reduced its reaction time significantly (P<0.05) at 1 and 10mM compared with the control, showing that 2PTS accelerated O(2)(-) generation in human PMNs. The difference in effects on O(2)(-) generation may be due to that in susceptibility to alk(en)yl thiosulfates between canine and human PMNs. On the other hand, NPTS and 2PTS were shown to significantly inhibit ADP-induced platelet aggregation at 0.01mM (P<0.01) in canine platelets and at 0.001-0.1mM (P<0.05) in human platelets. In contrast, the maximal aggregation percentage returned to the control level at 1mM of alk(en)yl thiosulfates in both canine and human platelets. From these results, we conclude that NPTS and 2PTS have the potential to promote immune functions and prevent cardiovascular diseases.

Adenosine Diphosphate↗
PubMed2004

Ethnic differences in the formation of small LDL particles in Asians: a comparison of Koreans, Japanese and Mongolians.

BACKGROUND: The presence of small, dense LDL particles has been recognized as an independent risk factor for coronary heart disease (CHD) but is not directly representative of CHD mortality rate beyond any given population. We investigated whether such inconsistency between three Asian ethnic groups might have arisen from anthropometric and metabolic factors. DESIGN: We conducted a cross-sectional survey among adult Koreans (412), Japanese (453) and Mongolians (253). RESULTS: The prevalence of small LDL particles was 36% in the Koreans, 21% in the Japanese and 7% in the Mongolians. Multiple logistic regression analysis revealed plasma triglyceride (TG) levels to be the strongest determinant of small LDL particle size in all three groups, with sex, HDL-cholesterol and non-HDL-C being other ethnic-specific significant determinants. Body mass index (BMI), FFA and insulin resistance were not significant factors in the regression analysis. Of the subjects with low TG levels (< 133 mg dL(-1)), 25% of the Koreans and 10% of the Japanese, but no Mongolians, had small LDL particles. CONCLUSIONS: Results of the present study suggest that traditionally, high-carbohydrate diets in Korea and Japan possibly contribute to higher TG-levels compared with BMI-matched Mongolians, and to the formation of small LDL particles, even in instances of low TG levels.

Adult↗
PubMed2004

SCP1, a 356,023 bp linear plasmid adapted to the ecology and developmental biology of its host, Streptomyces coelicolor A3(2).

The sequencing of the entire genetic complement of Streptomyces coelicolor A3(2) has been completed with the determination of the 365,023 bp sequence of the linear plasmid SCP1. Remarkably, the functional distribution of SCP1 genes somewhat resembles that of the chromosome: predicted gene products/functions include ECF sigma factors, antibiotic biosynthesis, a gamma-butyrolactone signalling system, members of the actinomycete-specific Wbl class of regulatory proteins and 14 secreted proteins. Some of these genes are among the 18 that contain a TTA codon, making them targets for the developmentally important tRNA encoded by the bldA gene. RNA analysis and gene fusions showed that one of the TTA-containing genes is part of a large bldA-dependent operon, the gene products of which include three proteins isolated from the spore surface by detergent washing (SapC, D and E), and several probable metabolic enzymes. SCP1 shows much evidence of recombinational interactions with other replicons and transposable elements during its history. For example, it has two sets of partitioning genes (which may explain why an integrated copy of SCP1 partially suppressed the defective partitioning of a parAB-deleted chromosome during sporulation). SCP1 carries a cluster of probable transfer determinants and genes encoding likely DNA polymerase III subunits, but it lacks an obvious candidate gene for the terminal protein associated with its ends. This may be related to atypical features of its end sequences.

Amino Acid Sequence↗
PubMed2004

Identification of differentially expressed genes involved in colorectal carcinogenesis using a cDNA microarray.

To identify candidate genes involved in human colorectal carcinogenesis, we constructed the gene expression profiles of 50 colorectal cancers (CRCs) and 12 normal colorectal epithelia using a cDNA microarray specially constructed for CRC. Hierarchical clustering analysis and principal component analysis could clearly distinguish the gene profiles of cancer tissues from those of normal tissues. Our results confirm there are indeed differences in gene expression between cancer and normal mucosa. Our cDNA microarray identified 22 up-regulated genes and 32 down-regulated genes in CRC. Many of these genes have been previously identified in relation to human carcinogenesis, 68% and 78%, respectively. Subsequent validation of selected genes by serial analysis of gene expression and reverse transcription polymerase chain reaction, demonstrated expression patterns that were almost identical to our microarray analysis. Using a four-fold larger sample relative to that used in our previous study, candidate genes involved in human colorectal carcinogenesis were reproducibly identified. Further studies of comprehensive gene expression using our technique may elucidate the mechanism of CRC tumorigenesis.

Cell Line, Tumor↗
PubMed2003

SulA-independent filamentation of Escherichia coli during growth after release from high hydrostatic pressure treatment.

To improve the efficiency of sterilization by high hydrostatic pressure treatment (HPT), it is desirable to know the biochemical process of bacteria most sensitive to the treatment. We investigated growth properties after release from HPT of exponentially growing Escherichia coli K-12 cells. We observed growth retardation after treatment (30 min at 37 degrees C) above 75 MPa. Long filamentous cells of about eight times normal cell length were observed at 90 min growth after treatment at 75 MPa. In the subsequent period the filamentous cells divided into normal-sized cells. recA and sulA mutant strains also formed filamentous cells, indicating that filamentation was SulA-independent. Nucleoids segregated normally in the filamentous cells. Only one FtsZ ring (or none) was detected at possible division sites in the elongated cells. Western blotting analysis demonstrated that the amount of FtsZ protein was not affected by the treatment. GTP-dependent in vitro polymerization of either FtsZ protein in E. coli crude extract or purified FtsZ protein, however, was sensitive to HPT. These facts suggest that HPT at 75 MPa denatures a fraction of FtsZ molecules, and that these denatured molecules interfere with the polymerization of functional FtsZ, resulting in the significantly reduced number of FtsZ rings.

Cell Division↗
PubMed2003

A primary retroperitoneal serous cystadenocarcinoma with clinically aggressive behavior.

CASE REPORT: We describe a 44-year-old woman with a primary retroperitoneal serous cystadenocarcinoma as the fourth report in the world literature. A contrast-enhanced computed tomographic scan of the abdomen demonstrated a mass with enhanced solid mural nodules and septa in the left retroperitoneum. Serum CA19-9 was elevated at 181 U/ml. The patient underwent a complete resection of the retroperitoneal tumor with a partial resection of the psoas major muscle and its fascia. Pathological examination showed a well-differentiated papillary serous cystadenocarcinoma of ovarian type and locoregional lymph node metastases. Seven months after surgery, the patient developed a pelvic recurrence, and underwent a total hysterectomy, a left salpingo-oophorectomy and a resection of the metastatic mesenteric mass. Two months after the second surgery, serum CA19-9 and CA125 increased to 1,114 U/ml and 218 U/ml, respectively. A solitary liver metastasis was confirmed on a computed tomographic scan. The patient is now being treated with weekly docetaxel and carboplatin. CONCLUSION: The present case illustrates the clinically aggressive nature of a primary retroperitoneal serous cystadenocarcinoma.

Adult↗
PubMed2003

Characteristics of the antihistamine effect of TAK-427, a novel imidazopyridazine derivative.

OBJECTIVE AND DESIGN: The characteristics of the antihistamine effect of the new antiallergic compound TAK-427 were investigated. MATERIALS AND METHODS: In vitro binding assay of [(3)H] pyrilamine was performed using recombinant human histamine H(1) receptors (rhH(1)R). In vivo studies were performed in male ICR mice or Hartley guinea pigs. Drugs were administered orally 1 h before examinations. Determinations were made of histamine-induced skin reaction, ex vivo measured radioligand binding to brain and lung H(1) receptors, pentobarbital-induced sleeping time, passive cutaneous anaphylaxis (PCA) reaction, and antigen-induced itch-scratch responses (ISRs). RESULTS: TAK-427 inhibited ligand binding to rhH(1)R with an IC(50) value of 17.3 nmol/l. TAK-427 inhibited histamine-induced skin reactions in guinea pigs and mice with an ID(50) value of 0.884 and 0.450 mg/kg, p.o., respectively; significant inhibition associated with 10 mg/kg of TAK-427 was still observed 24 h after dosing in guinea pigs. TAK-427 showed as high selectivity for peripheral H(1) receptors as terfenadine and epinastine did, which was evaluated by ex vivo measured radioligand binding. Even at 300 mg/kg, TAK-427 did not affect pentobarbital-induced sleeping time in mice. TAK-427 significantly inhibited PCA in mice and guinea pigs, and also inhibited antigen-induced ISRs in guinea pigs. CONCLUSIONS: These results suggest that TAK-427 may have a long-lasting antihistamine activity with minimum sedative side effect and suppress acute phase allergic reactions.

Algorithms↗
PubMed2003

The effect of high sugar intake on the development of periradicular lesions in rats with type 2 diabetes.

Diabetes mellitus is associated with depression of natural defenses against infection and increases the risk of periodontal disease. However, the effects of diabetes on periradicular tissue, which differs structurally from periodontal tissue, are not known. In this study, we evaluated the effects of type 2 diabetes on the development of periradicular lesions after exposure of the pulp in the left mandibular first molar through the occlusal surface in rats. GK rats with spontaneous non-insulin-dependent diabetes mellitus and Wistar rats (controls) received a normal laboratory diet and either water or a 30% sucrose solution. At both 2 and 4 weeks after pulp exposure, histologic analysis showed that alveolar bone resorption was most severe and the periradicular lesions were largest in diabetic rats given the sucrose solution. These results suggest that the metabolic conditions produced by type 2 diabetes enhance the development of periradicular lesions in rats.

Alveolar Bone Loss↗
PubMed2002

Molecular cloning and phylogenetic analysis of Babesia gibsoni heat shock protein 70.

The Babesia gibsoni heat shock protein 70 gene (BGHsp70) was cloned by polymerase chain reaction (PCR) and sequenced. The length of the gene was 1938 bp and the predicted polypeptide was 646 amino acids long with a calculated molecular weight of 70,627. The amino acid sequences of BGHsp70 from 17 isolates were identical, though there were six types of polymorphisms among the corresponding nucleotide sequences. There was no intron in the BGHsp70 gene. Phylogenetic analysis of the amino acid sequence of Hsp70 showed that B. gibsoni was most closely related to B. bovis and lies within a phylogenetic cluster with Theileria. These results suggest that Hsp70 was well conserved among intraerythrocytic protozoa.

Amino Acid Sequence↗
PubMed2002

KL-6 as an indicator for lymphocytic interstitial pneumonia (LIP) in a human T-lymphotrophic virus type 1 (HTLV-1) carrier.

A 59-year-old woman was admitted to our hospital complaining of a productive cough, dyspnea on effort, and low-grade fever. Although chest X-rays showed no marked abnormalities, her level of serum KL-6 was extremely high. We therefore suspected the presence of interstitial pneumonia. High-resolution computed tomography (CT) scan revealed infiltrative shadows in S6 of the right lung, and her serum was positive for antihuman T-lymphotropic virus type 1 (HTLV-1) antibodies. From the clinical symptoms, radiographic findings, and histological findings, the diagnosis was probable lymphocytic interstitial pneumonia (LIP). After high-dose corticosteroid therapy, the level of serum KL-6 decreased rapidly. We conclude that KL-6 is a convenient and reliable marker for evaluating the activity of pulmonary manifestations in HTLV-1 carriers and that it is especially useful in monitoring the effectiveness of treatments.

Adrenal Cortex Hormones↗
PubMed2002

Enhanced tumor cell selectivity of adriamycin-monoclonal antibody conjugate via a poly(ethylene glycol)-based cleavable linker.

A novel linker consisting of poly(ethylene glycol) (PEG) and dipeptide was used for conjugation of adriamycin with tumor-specific monoclonal antibody, NL-1, to confirm that the linker can be cleaved selectively with the tumor specific enzyme to express cytotoxicity of the anti-tumor agent. Initially, adriamycin-conjugated PEG linkers through different amino acid compositions, alanyl-valine (Ala-Val), alanyl-proline (Ala-Pro), and glycyl-proline (Gly-Pro) sequences, were prepared to confirm selective digestion with model enzymes. Adriamycin was released by particular model endoproteases, thermolysin and proline endopeptidase, from the linkers with different efficiency. When conjugates were prepared using these adriamycin-bound linkers, conjugates had no loss of binding affinity and specificity for common acute lymphoblastic leukemia antigen (CALLA) expressed on the Daudi cell surfaces as the target of NL-1 antibody. In addition, adriamycin release from the conjugates was also confirmed by incubating them with specific proteases. Tumor cell growth was inhibited dose-dependently for the conjugates carrying Ala-Val and Gly-Pro linkers, whereas significant inhibitory effect was abolished for the conjugate carrying Ala-Pro linker, indicating that cytotoxic effect can be controlled by specificity of antibody and composition of linker peptide. IC(50) for Ala-Val linked conjugate was approximately 3.5 microg/ml and that for Gly-Pro linked conjugate was 5.2 microg/ml. PEG-dipeptidyl linker demonstrated here will be an effective tool for the preparation of immunoconjugate, especially specific activation of anti-tumor agents at desired tumor tissues.

Antibodies, Monoclonal↗
PubMed2002

Protruding atherosclerotic aortic plaques and dyslipidaemia: correlation to subtypes of ischaemic stroke.

AIMS: To evaluate whether thoracic aortic plaques together with dyslipidaemia are related to ischaemic stroke, and if so, to which of the subtypes of stroke. METHODS AND RESULTS: We performed transoesophageal echocardiography in 50 patients with acute ischaemic stroke and in 401 controls. The aorta was divided into two segments: (1) the proximal, proximal to the left subclavian artery, and (2) the distal aorta. Protruding plaques (Intima > or =4 mm in thickness) in the proximal aorta were detected in 14 of the 50 patients (28%) with stroke, and in 53 of the 401 controls (13%) (P<0.01). Plaque score in the proximal aorta (2.1 +/- 1.8 vs 0.9 +/- 0.7; P<0.05), low-density lipoprotein cholesterol level (3.60 +/- 0.85 vs 2.87 +/- 0.72 mmol/l; P<0.05), and apolipoprotein B/A-I ratio (0.98 +/-0.17 vs 0.73 +/- 0.16; P<0.005) were higher in patients with athero-thrombotic than in cardioembolic stroke. The score in the proximal aorta correlated with low-density lipoprotein cholesterol level (r=0.44, P<0.005) and apolipoprotein B/A-I ratio (r=0.40, P<0.01). CONCLUSION: Severe plaques in the proximal aorta together with dyslipidaemia are seen more frequently in patients with atherothrombotic stroke. Lipid analysis may contribute to the prediction and the treatment of the patients who are at high risk for atherothrombotic stroke.

Acute Disease↗
PubMed2002

Augmented binding and activation of latent transforming growth factor-beta by a tryptic fragment of latency associated peptide.

Transforming growth factor-beta (TGF-beta) is secreted in a latent form; thus, activation is critical for the control of TGF-beta action. Latent TGF-beta exists in a complex in which mature TGF-beta is noncovalently linked to latency associated peptide (LAP) and latent TGF-beta binding protein (LTBP) complex. We have shown that latent TGF-beta is efficiently activated in heterotypic cultures of endothelial cells (ECs) and smooth muscle cells (SMCs). Under those conditions, LAP plays an important role in targeting latent TGF-beta to the surface of SMCs, and plasmin and calpain target it to the surface of ECs for activation. Here, we demonstrate in a homotypic culture system that fragments of LAP increase the binding of latent TGF-beta to ECs, resulting in its activation by cell-associated proteolysis. LAP fragments appear to bind to the cell surface and augment the binding of latent TGF-beta, independent of transglutaminase. These results suggest a unique mechanism for the activation of latent TGF-beta by proteolytic fragments of LAP. The mechanism may arise from degradation by elevated levels of proteases under certain conditions.

Amino Acid Sequence↗
PubMed2001

Aqua[N-(6-carboxylato-kappa O-pyridine-2-carbonyl-kappa N)-L-histidinato-kappa(2)N,N']copper(II).

The title compound, [Cu(C(13)H(10)N(4)O(5))(H(2)O)], is an asymmetric and pentacoordinated square-pyramidal copper(II) complex, with a water molecule occupying an apical position. It consists of syn and anti isomers of the apical water molecule with respect to the metal-free carboxyl group on the equatorial ligand. The crystal structure of this complex is a rare example of conformational isomerization, in which the two isomers cocrystallize in a 1:3 ratio of syn to anti molecules in the same lattice.

Journal Article↗
PubMed2001

Specific targeting, biodistribution, and lack of immunogenicity of chimeric anti-GD3 monoclonal antibody KM871 in patients with metastatic melanoma: results of a phase I trial.

PURPOSE: KM871 is a chimeric monoclonal antibody against the ganglioside antigen GD3, which is highly expressed on melanoma cells. We conducted an open-label, dose escalation phase I trial of KM871 in patients with metastatic melanoma. PATIENTS AND METHODS: Seventeen patients were entered onto one of five dose levels (1, 5, 10, 20, and 40 mg/m2). Patients received three infusions of KM871 at 2-week intervals, with the first infusion of KM871 trace-labeled with indium-111 (111In) to enable assessment of biodistribution in vivo. Biopsies of metastatic melanoma sites were performed on days 7 to 10. RESULTS: Fifteen of 17 patients completed a cycle of three infusions of KM871. No dose-limiting toxicity was observed during the trial; the maximum-tolerated dose was therefore not reached. Three patients (at the 1-, 5-, and 40-mg/m2 dose levels) developed pain and/or erythema at tumor sites consistent with an inflammatory response. No normal tissue uptake of 111In-KM871 was observed, and tumor uptake of 111In-KM871 was observed in all lesions greater than 1.5 cm (tumor biopsy 111KM871 uptake results: range, 0.001% to 0.026% injected dose/g). The ratio of maximum tumor to normal tissue was 15:1. Pharmacokinetic analysis revealed a 111In-KM871 terminal half-life of 7.68 +/- 2.94 days. One patient had a clinical partial response that lasted 11 months. There was no serologic evidence of human antichimeric antibody in any patient, including one patient who received 16 infusions over a 12-month period. CONCLUSION: This study is the first to demonstrate the biodistribution and specific targeting of an anti-GD3 antibody to metastatic melanoma in patients. The long half-life and lack of immunogenicity of KM871 makes this antibody an attractive potential therapy for patients with metastatic melanoma.

Adult↗