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Biomedical subjects

K Kurosawa

Publications and source records attributed to K Kurosawa.

At least 91 records · Page 5Linked to original sources

Thrombotic thrombocytopenic purpura developed suddenly during interferon treatment for chronic hepatitis C.

A 57-year-old man had abnormal hepatic function identified in April 1994. In October 1994, chronic hepatitis C was diagnosed. Based on the findings of a liver biopsy, administration of recombinant interferon (rIFN)-alpha2b was begun. In the 16th week of treatment, the patient experienced headache and fever and developed a markedly decreased, platelet count and hemolytic anemia. He was admitted on May 19, 1995 and thrombotic thrombocytopenic purpura (TTP) was diagnosed. He died on the 3rd hospital day. The causes of TTP have yet to be elucidated, but in this patient the occurrence of TTP appeared to be related to the IFN treatment for chronic hepatitis C.

Antiviral Agents↗

Familial lobular glomerulopathy: first case report in Asia.

A 23-year-old male Japanese student presented a unique lobular glomerulopathy characterized by mesangial and subendothelial expansion with numerous periodic acid-Schiff-positive deposits. Electron microscopy showed massive fine granular deposits with a homogeneous distribution. Fibrillar or microtubular structures were not demonstrated. Fibronectin was positive on immunostaining, as was immunoglobulin G and fibrinogen. Familial study revealed that the patient's grandfather, two aunts, and one cousin on his father's side had developed end-stage renal failure. Clinicopathologic features of this patient are identical with those of familial lobular glomerulopathy, which has been previously described by several investigators. Seven of the previously reported families were white and resided in the United States or in European countries. This is the first report of an Asian case, and indicates that this disease universally occurs independently of racial specificity.

Adult↗

Apoptosis in feline panleukopenia virus-infected lymphocytes.

Feline panleukopenia virus (FPLV) was shown to induce apoptosis to feline lymphoid cells and to reduce the expression of interleukin-2 receptor alpha on the cells. FPLV-induced apoptosis might be a key element in the pathophysiology of atrophy of lymphoid tissues associated with feline panleukopenia caused by FPLV.

Animals↗

Further development of a recombinant feline herpesvirus type 1 vector expressing feline calicivirus immunogenic antigen.

We previously reported the attenuation of thymidine kinase (TK) deficient mutant (C7301dlTK) of feline herpesvirus type 1 (FHV-1) in cats and the construction of a recombinant FHV-1 (C7301dlTK-Cap) inserted a precursor capsid gene of feline calcivirus (FCV) into the TK deletion locus of the C7301dlTK. In this study, we constructed a further improved recombinant FHV-1 (dlTK(gCp)-Cap) carrying a putative FHV-1 gC promoter sequence upstream of the FCV precursor capsid gene of the C7301dlTK-Cap. Growth kinetics of the dlTK(gCp)-Cap in cell cultures was similar to those of C7301dlTK and C7301dlTK-Cap. A strong expression of FCV immunogenic antigen by dlTK(gCp)-Cap was confirmed by indirect immunofluorescence and enzyme-linked immunosorbent assays. In addition, one vaccination with dlTK(gCp)-Cap protected cats more effective against subsequent virulent FCV challenge than that with C7301dlTK-Cap.

Animals↗

New quantitative methods for detection of feline parvovirus (FPV) and virus neutralizing antibody against FPV using a feline T lymphoid cell line.

Previously, we reported that a feline T lymphoid cell line, FL74 cells, was very sensitive to feline parvovirus (FPV) infection. In the present study, we developed new quantitative methods for detection of FPV and virus neutralizing antibody against FPV using FL74 cells. The methods presented here were very simple and applicable to both canine parvovirus and feline panleukopenia virus.

Animals↗

[The significance of 123I-BMIPP myocardial SPECT on the evaluation of angina pectoris].

Some patients of ischemic heart disease have low uptake in 123I-labeled beta methyl-iodophenyl penta-decanoic acid (BMIPP) SPECT in spite of normal uptake in thallium-201 (Tl) SPECT. To investigate their clinical significance, we performed both T1 and BMIPP myocardial SPECT in 26 cases with stable angina (n = 16) and unstable angina (n = 10), and compared with clinical backgrounds electrocardiogram (ECG) and left ventriculography (LVG). In 11 patients of them, the uptake of BMIPP was moderately reduced. We divided 26 cases into two groups according to uptake of BMIPP (normal/reduced). The two groups had no differences in length of angina attack and duration of disease, but they had a significant difference in the abnormality of either ECG or LVG. Three to six months after PTCA, we examined LVG in 18 cases, 12 of 16 cases with the abnormality of LVG showed the improvement of wall motion. We concluded the reduced uptake of BMIPP with normal uptake of Tl was related to more severe ischemia in cases with unstable angina.

Aged↗

Endoscopic follow-up study of development of gastric antral vascular ectasia associated with liver cirrhosis.

Gastric antral vascular ectasia is an important cause of chronic gastrointestinal blood loss. However, its development and progression have not yet been clarified. We investigated its early lesions and progression by reviewing endoscopic films of five patients with gastric antral vascular ectasia followed for liver cirrhosis. In all patients, early findings were prepyloric red spots. In two patients, anemia due to gastrointestinal bleeding was already observed when vascular lesions were confined to the distal antrum. In the other three patients, anemia was observed 1-2 years after they showed a diagnostic pattern of gastric antral vascular ectasia. The vascular lesions gradually thickened and extended throughout the antrum, with the complete picture shown in 1.5-5 years. The pattern of distribution was classified into three types: diffuse spotty, diffuse confluent, and striped. These types could be predicted before the complete formation. Gastric antral vascular ectasia associated with liver cirrhosis started as prepyloric red spots and extended to the proximal antrum in various ways and varying time courses of less than 5 years; this entity may cause hemorrhage even in the early stage.

Aged↗

Evaluation of combined therapy with chemoembolization and ethanol injection for advanced hepatocellular carcinoma.

To evaluate the therapeutic efficacy of transcatheter arterial chemoembolization (TACE) combined with percutaneous ethanol injection therapy (PEIT) for advanced hepatocellular carcinoma, we studied the effectiveness of TACE therapy combined with PEIT (50 cases) and TACE alone (50 cases). In both groups, patients had multiple lesions, or a single lesion with a diameter exceeding 2 cm or with vascular invasion (stages II, III, and IV in the tumor staging classification of the Liver Cancer Study Group of Japan). The clinical features in the two groups were comparable. The cumulative survival rates with TACE-PEIT were 95.0% for 1 year, 72.5% for 2 years, and 50.0% for 3 years, whereas the rates with TACE alone were 92.5% for 1 year, 57.5% for 2 years, and 20.0% for 3 years. The survival rate in the TACE-PEIT group was significantly higher than that in the TACE alone group. Moreover, the survival rate of patients with stage II or III disease in the TACE-PEIT group was significantly better than that in the TACE alone group, and the survival rate of patients with Child's classification B or C in the TACE-PEIT group was significantly higher than that in the TACE alone group. Multivariate analysis using Cox's proportional hazard regression model showed that the most significant prognostic factors in the TACE-PEIT group were tumor embolus in the portal vein and the number of tumors. These results suggest the effectiveness of combining TACE and PEIT for the treatment of advanced hepatocellular carcinoma.

Antibiotics, Antineoplastic↗

Immobilized anti-KIT monoclonal antibody induces ligand-independent dimerization and activation of Steel factor receptor: biologic similarity with membrane-bound form of Steel factor rather than its soluble form.

Interaction of a tyrosine kinase type receptor and its ligand induces receptor-dimerization or -oligomerization followed by transphosphorylation and activation of its intrinsic kinase, which leads to a series of intracellular signals. We have previously reported that the membrane-bound form of Steel factor (SLF) induces more persistent tyrosine kinase activation and longer life span of c-kit encoded protein (KIT) than its soluble form (Miyazawa et al, Blood 85:641, 1995). In this study, we used YB5.B8 monoclonal antibody (MoAb) that recognizes the extracellular domain of KIT to investigate whether immobilized anti-KIT MoAb can substitute for SLF as a potent activator of KIT by cross-linking receptors and further compared its effect with each SLF isoform in a factor-dependent cell line M07e. YB5.B8 MoAb in a soluble state suppressed SLF-induced M07e cell proliferation in a dose-dependent manner. By contrast, once this antibody was immobilized on the goat-antimouse MoAb (GAM)-coated culture plates, it supported the growth of M07e cells in the absence of any growth factors, whereas culture the cells in GAM alone or YB5.B8 without GAM-coated plates resulted in rapid cell-death within 24 hours. As with the natural ligand SLF, immobilized YB5.B8 MoAb synergized with granulocyte-macrophage colony-stimulating factor (GM-CSF) in inducing cell proliferation compared with either YB5.B8 MoAb or GM-CSF alone. Immunoblotting with antiphosphotyrosine MoAb showed that interaction of M07e cells with immobilized YB5.B8 induced tyrosine phosphorylation of a series of intracellular proteins including KIT (145 kD). In addition, cross-linking studies using a water-soluble cross linking reagent bis-sulfosuccinimidyl-suberate showed that immobilized YB5.B8 MoAb induced dimerization and activation of KIT. However, as with stimulation by the membrane-bound form of SLF, the kinetics of KIT activation with YB5.B8 MoAb was more prolonged compared with the cells treated with recombinant soluble SLF. Flow cytometry showed that, unlike the cells treated with soluble SLF, no downmodulation of cell-surface KIT expression was observed in M07e cells cultured with immobilzed YB5.B8 MoAb. These data suggest that immobilized antibodies against hematopoietic receptors may replace their ligand-stimulators; however, their activities may resemble the membrane-bound form rather than the soluble form of natural ligands.

Amino Acid Sequence↗

Structure-activity relationships of neuromedin U. III. Contribution of two phenylalanine residues in dog neuromedin U-8 to the contractile activity.

Dog neuromedin U-8 (d-NMU-8; pGlu-X2-Leu-Y4-Arg-Pro-Arg-Asn-NH2, X = Y = Phe) has potent biological activity to stimulate an isolated chicken crop smooth muscle preparation with the relative activity (RA value) of 5.78 to porcine neuromedin U-8 (p-NMU-8). To elucidate the contribution of the two phenylalanine residues of NMU-8 to the biological activity, fourteen d-NMU-8 analogs modified either at position 2 or 4, [X2]- or [Y4]-d-NMU-8, were synthesized, where X and Y were Ala, Tyr, Trp, Thr, Glu, His or cyclohexylalanine (Cha). Most of the analogs retained very low contractile activity, suggesting the importance of both Phe residues in d-NMU-8 for the biological activity. [X2]-d-NMU-8 analogs had lower biological activity in terms of the RA value than the corresponding [Y4]-d-NMU-8, when X and Y are the same amino acid. Loss of aromaticity of Phe2 ([Cha2]-d-NMU-8) resulted in a marked decrease of the contractile activity, while that of Phe4 ([Cha4]-d-NMU-8) resulted in retention of considerable activity, with the RA value of 2.68. [Tyr4]-d-NMU-8 was an exceptional analog with higher contractile activity (p < 0.01) than the parent compound d-NMU-8, having the RA value of 12.6. The results indicated that the aromatic side chain of the Phe residue at position 2 contributes more than that at position 4 to the biological activity.

Amino Acid Sequence↗

Effect of phenytoin on cortical Na(+)-K(+)-ATPase activity in global ischemic rat brain.

Na(+)K(+)-ATPase activity, water content, and Na+/K+ concentrations in the parietal cortex were measured in untreated and phenytoin-treated rats following global cerebral ischemia. Inhibitory effects of phenytoin treatment on brain edema and changes in Na(+)-K+ concentration with ischemia or ischemia followed by recirculation of varying intervals were assessed. The cortical Na(+)-K(+)-ATPase activity increased in the phenytoin-treated group during and after ischemia. Based on these results, we conclude that phenytoin provides ischemic brain protection by activating cortical Na(+)-K(+)-ATPase activity and by reducing intracellular Na+ and water content.

Animals↗

Structure-activity relationships of neuromedin U. I. Contractile activity of dog neuromedin U-related peptides on isolated chicken crop smooth muscle.

Synthetic dog neuromedin U-25(d-NMU-25), U-8(d-NMU-8) and their fragments wer examined for contractile activity on chicken crop smooth muscle preparation. The relative activities of d-NMU-25, d-NMU-25(15--25)NH2 and d-NMU-8 to porcine neuromedin U-8 (p-NMU-8) were 1.69, 2.54 and 5.78, respectively. High activity of d-NMU-8 may be attributable to the N-terminal pGlu residue, which provides resistance to aminopeptidases. Various NMU-8 analogs, having various amino acids, N alpha-acetylated amino acids, D-amino acids, or simple organic acids at position 1, were synthesized and evaluated for contractile activity. None of the substitutions caused a significant decrease of the biological activity. Modification at the N-terminal to give aminopeptidase resistance produced analogs with increased contractile activity, presumably because they were not degraded by soluble enzymes released into the bioassay fluid from isolated chicken crop tissue.

Amino Acid Sequence↗

Structure-activity relationships of neuromedin U. II. Highly potent analogs substituted or modified at the N-terminus of neuromedin U-8.

To develop a highly potent agonist and to examine the structure-contractile activity relationship of neuromedin U-8(NMU-8), seventeen analogs were synthesized and tested for contractile activity on isolated chicken crop smooth muscle preparations. The analogs were designed to examine the contributions of cyclic structure and acidic function at the N-terminal of NMU-8 and NMU-8(2--8) to the biological activity. The relative activity (RA) values of NMU-8 analogs were as follows: [Dp-Glu1]-NMU-8,5.50; [pyrohomoglutamyl(pHgu)1]-NMU-8,4.65;[D-pHgu1]-NMU-8, 4.66; [Asp1]-NMU-8, 11.4; [acetyl(Ac)-Asp1]-NMU-8, 9.81; [Ac-Glu1]- NMU-8, 18.6; [succinyl (Suc)-Tyr1-NMU-8,69.3; [3-sulfoalanyl (Sal)1]-NMU-8, 12.7. The RA values of NMU-8(2--8) analogs were as follows: alpha-picolinyl (Pic)-NMU-8 (2--8), 7.96; 2-furoyl (Fur)-NMU-8, (2--8), 9.91; 2-thiophenecarboxyl (Thi)-NMU-8 (2--8), 3.41; 4-hydroxyphenylpropionyl (Hpp)-NMU-8(2--8), 3.20; o-phthalyl (Pht)-NMU-8 (2--8), 11.3; Suc-NMU-8 (2--8), 109; malonyl (Mlo)-NMU-8 (2--8), 17.9; maleyl (Mle)-NMU-8 (2--8), 31.6; glutaryl (Glt)-NMU-8 (2--8), 81.3; The potencies of the analogs were higher than that of p-NMU-8. Suc-NMU-8 (2--8) showed the highest potency among the analogs synthesized. The results reveal that the carboxylic acid group at the N-terminus of NMU-8 makes a major contribution to the activity.

Amino Acid Sequence↗