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Biomedical subjects

T Ohkawa

Publications and source records attributed to T Ohkawa.

At least 73 records · Page 4Linked to original sources

High concentration of recombinant murine interferon-beta enhances the growth of Orientia (formerly Rickettsia) tsutsugamushi Gilliam in mouse L929 cells.

We studied the effect of recombinant murine interferons (rMuIFNs) on the growth of Orientia (formerly Rickettsia) tsutsugamushi Gilliam in mouse L929 cells. Rickettsial growth was measured by flow cytometry. rMUIFN-gamma inhibited the growth of O. tsutsugamushi at the concentrations of 100 i.u./ml and 1,000 i.u./ml in accord with previous reports. Relatively low concentrations (10 i.u./ml and 100 i.u./ml) of rMUIFN-beta also inhibited the growth of O. tsutsugamushi. On the other hand, high concentrations (1,000 i.u./ml and 10,000 i.u./ml) of rMuIFN-beta enhanced the growth of the rickettsia. This enhancement of rickettsial growth was blocked by anti-murine IFN-beta monoclonal antibody (MoAb). rMuIFN-beta also enhanced the growth of Rickettsia sibirica 246 in L929 cells to some extent.

Animals↗

[Clinical phase III study of cimetropium bromide (DA3177) on the pain with upper urinary calculus: a double-blind study in comparison with scopolamine butylbromide. DA3177 Study Group].

A double-blind study was conducted to evaluate the efficacy, safety and usefulness of cimetropium bromide (DA3177) in the patients with pain caused by upper urinary calculus at a daily dose of 75 mg t.i.d. (Group D, 97 patients) in comparison with scopolamine butylbromide at a daily dose of 60 mg t.i.d. (Group B, 101 patients). According to patient's impression, the rate of "moderately improved" or better was significantly higher in Group D (68.7%) than in Group B (53.5%; Wilcoxon 2 sample test: p = 0.0044). For pain, the rate of "moderately improved" or better was 69.1% in Group D and 60.4% in Group B. In global improvement, the rate of "moderately improved" or better was significantly higher in Group D (70.1%) than in Group B (61.4%; Wilcoxon 2 sample test: p = 0.0469). The rate of "no problem in safety" showed no significant difference between Group D (91.5%) and Group B (93.3%). Adverse reactions occurred in 8.5% in Group D and 6.7% in Group B. The major adverse reactions were "dry mouth", "abdominal distension", "constipation" and "nausea". The rate of "useful" or better was 68.7% in Group D, and 60.4% in Group B. In conclusion, DA3177 was confirmed to be a useful drug for patient with pain caused by upper urinary calculus.

Adult↗

Tissue-specific expression of an anti-ras ribozyme inhibits proliferation of human malignant melanoma cells.

In this study, we have compared the efficacy of a tissue-specific promoter (tyrosinase promoter) with a viral promoter to express anti-ras ribozyme RNA in human melanoma cells. The retroviral vector containing the tyrosinase promoter was superior in its ability to suppress the human melanoma phenotype in vitro as characterized by changes in growth, melanin synthesis, morphology and H-ras gene expression. These data support the use of tissue-specific expression of anti-oncogene ribozymes as a rational therapeutic strategy in human cancers.

Base Sequence↗

Interactions between calcium oxalate monohydrate crystals and Madin-Darby canine kidney cells: endocytosis and cell proliferation.

The present investigation was designed to study the biological responses in cultures of Madin-Darby canine kidney (MDCK) cells exposed to calcium oxalate monohydrate (COM) crystals, the most common type of urinary crystals. The addition of COM crystals significantly accelerated the multiplication of MDCK cells and significantly activated the cell viability. After exposure of MDCK cells to COM crystals, scanning electron microscopy revealed that some crystals adhered to the plasma membrane and others were endocytosed by the cell. This cellular uptake of crystals was time dependent from 1 to 8 h and showed a specificity according to crystal type. However, the endocytosis of aggregated COM crystals was less marked than that of non-aggregated crystals. Pre-treatment with each of the glycosaminoglycans (sodium pentosan polysulphate, heparin, and chondroitin sulphate C) produced a significant reduction of the cellular uptake of COM crystals, suggesting that these glycosaminoglycans may play some critical roles in preventing the cellular uptake of crystals. Although investigation in further detail is necessary, we speculate that these crystal-cell interactions, that is, the cellular uptake of crystals and cell proliferation, may be among the earliest processes in the formation of kidney stones.

Animals↗

Cancer-associated retinopathy in a patient with endometrial cancer.

PURPOSE: We studied a case of unusual retinopathy in a 60-year-old woman. METHOD: The patient developed bilateral retinopathy with iridocyclitis and vitreitis. Corticosteroid therapy could not prevent deterioration of visual acuity and field. The electroretinogram became nonrecordable, and fluorescein angiogram exhibited retinal pigment epithelium window defects, fluorescein stainings to the vascular walls, and narrowed arterioles. RESULTS: The patient underwent hysterectomy and lymphadenectomy for endometrial cancer in the corporis uteri. She was found to possess antibodies against retinal 34-kd protein, leading to a diagnosis of cancer-associated retinopathy. CONCLUSION: Cancer-associated retinopathy may occur in patients with endometrial cancer of the corporis uteri.

Antibodies, Neoplasm↗

Nonhuman primate models of measles.

Wild measles virus isolated in a marmoset lymphoblastoid B95a cell line induced rashes and Koplik's spots when inoculated parenterally in cynomolgus and squirrel monkeys. Marked leukopenia. associated with transient decrease in the CD4(+)-to-CD8+ T-cell ratio also was induced. Virus growth, as well as histologic lesions of necrosis and giant cell formation, was observed in the lymphoid tissues. Thus clinical signs of acute measles were successfully induced in monkeys by inoculation with cell-culture-grown measles virus. These nonhuman primate models of measles will be useful for study of the pathogenesis of acute measles virus infection in terms of generalized clinical signs of disease, leukopenia, and changes in the lymphocyte subsets.

Animals↗

Adhesion and endocytosis of calcium oxalate crystals on renal tubular cells.

The present investigation was designed to study interactions between Madin-Darby canine kidney (MDCK) cells and calcium oxalate monohydrate (COM) crystals and to clarify the significance of these crystal-cell interactions in stone pathogenesis. MDCK cells cultured in the presence of COM crystals showed a time-dependent uptake of crystals; this was specific for COM crystals. In the dynamic model system designed to study these phenomena under more physiological conditions, COM crystals adhered to the cell surface and were subsequently internalized. In this endocytotic process, the microvilli of the cell appeared to play an important role. The observation by scanning electron microscopy of complexes consisting of aggregated COM crystals and cell debris led us to speculate that adhesion and endocytosis of crystals might provide the calculus nidus for aggregation and retention of crystals in the renal tubule. Furthermore, glycosaminoglycans and the macromolecular fraction of human urine were shown to have the ability to inhibit the cellular uptake of crystals. Evidence that similar processes may also occur in vivo was obtained using an experimental stone model in rats. Our experiments revealed that most of the COM crystals adhered to the tubular cells and some crystals were endocytosed by the cell. Thus, these crystal-cell interactions might be one of the earliest processes in the formation of kidney stones. Further elucidation of the mechanism and the regulatory factors involved in this process may provide new insight into stone pathogenesis.

Adhesiveness↗

Binding mode of N,N',N",N"'-tetraacetylchitotetraitol to hen egg white lysozyme.

The binding of N,N',N",N"'-tetraacetylchitotetraitol [(GlcNAc)4-ol] to hen egg white lysozyme was investigated by fluorescence and 1H NMR spectroscopy. From observation of changes in the fluorescence intensity, the association constants of (GlcNAc)4-ol and (GlcNAc)3 were found to be 0.70 x 10(5) and 1.07 x 10(5) M-1, respectively, at pH 5.0 and 30 degrees C. The lack of a substantial difference between the association constants suggests that the binding mode of the (GlcNAc)3 moiety of (GlcNAc)4-ol is basically similar to that of (GlcNAc)3, but that the N-acetylglucosaminitol residue of (GlcNAC)4-ol does not interact significantly with lysozyme. On the other hand, 1H NMR spectroscopy revealed a minor difference in the binding modes of the two saccharides. For most of the 1H signals responding to saccharide binding, such as those of Trp 63 H2, Trp 28 H5, and Ile 98 H gamma 1, the chemical shift changes induced by (GlcNAc)4-ol were almost identical to those induced by (GlcNAc)3. However, the effect of binding on the signals of Asn 59 H alpha and Trp 108 indole N1H, which are located near subsite C, was different for (GlcNAc)4-ol and (GlcNAc)3. Thus it is inferred that the binding mode of the first sugar residue of (GlcNAc)4-ol to subsite C is somewhat different from that of (GlcNAc)3.

Animals↗

Therapeutic applications of ribozymes.

The demonstration that RNA can be cleaved by cis or trans ribozymes (catalytic RNAs, RNA enzymes) has potentially important therapeutic implications. Since their discovery in the 1980s, the biochemistry and conserved sequences of ribozymes have been well characterized. Ribozymes are effective modulators of gene expression because of their simple structure, sitespecific cleavage activity, and catalytic potential. The targets of ribozyme-mediated gene modulation have ranged from cancer cells to foreign genes that cause infectious diseases. Additional target sites for ribozymes are in initial phases of development and design. Ribozymes have been targeted against a myriad of genes, including oncogenes (ras, BCR-ABL, c-fos) and drug resistance genes, as well as the human immunodeficiency virus-type I genome. These ribozymes have cleaved the target RNAs in vitro and altered the cellular pathology. Currently, the therapeutic application of ribozymes to human diseases is limited by gene transfer systems. It is anticipated that ribozymes ultimately will play an important role in human gene therapy.

Acquired Immunodeficiency Syndrome↗

Response to interferon therapy in children with chronic hepatitis C.

We evaluated the effect of interferon therapy and investigated factors that may influence the outcome in 18 children with chronic hepatitis C. A complete response was obtained in 10 children (56%). The titer for pretreatment serum virus ribonucleic acid (< or = 10(7) copies/ml) was correlated significantly with a complete response to therapy.

Alanine Transaminase↗

Oligonucleotide-mediated modulation of mammalian gene expression.

The notion that oligonucleotides can modulate gene-specific expression was established more than a decade ago. Recent advances in molecular genetics have broadened the armamentarium used to manipulate gene expression in biological systems including triplex DNA, antisense RNA/DNA, and ribozymes (catalytic RNA). These oligonucleotides demonstrated important early application to the elucidation of cellular signaling pathways. More recently, studies with these agents have probed their utility as potential therapeutic agents, especially in the realm of cancer. With the implementation of gene therapy in early clinical trials, oligonucleotide-mediated suppression of gene expression has emerged as an important strategy for gene therapy. This review will discuss the current knowledge in this field, focusing on the biology of triplex DNA, antisense oligonucleotides, and ribozymes.

Animals↗

Determination of salivary cortisol by ELISA and its application to the assessment of the circadian rhythm in children.

In 35 young children, circadian rhythms of salivary cortisol levels were determined by ELISA using a commercially available kit with a minor modification. The concentration of labeled cortisol in the serum kit was reduced in order to measure cortisol in 10 microliters of saliva. Intra- and interassay coefficients of variation for salivary cortisol ranged from 2.4 to 9.9 and 3.2 to 8.9%, respectively. Recovery of salivary cortisol was 82.9-107.0%. There was a highly significant correlation between cortisol levels in saliva and serum in adults (r = 0.857). Salivary cortisol levels ranged from 0.01 to 2.252 micrograms/100 ml and showed significant diurnal variation in the children. Our ELISA is a precise, simple, noninvasive and useful method for clinical practice and study in infants and children.

Adult↗

Adhesion of calcium oxalate crystals to Madin-Darby canine kidney cells and some effects of glycosaminoglycans or cell injuries.

The present investigation studied the quantitative adhesion of calcium oxalate monohydrate (COM) crystals to the surface of Madin-Darby canine kidney cells, which exhibit many characteristics of renal cortical collecting tubule cells. COM crystals adhered to the cell surface, and the attachment showed a time and concentration dependency with plateau. The results suggested that the attachment of microcrystals to the cortical tubular cell might be one of the earliest processes in the formation of kidney stones. Pretreatment with glycosaminoglycans significantly reduced the adherent crystals. Injuries to the Madin-Darby cells induced by 0.1 M HCl and gentamicin resulted in significant decreases of COM crystal adhesion to the cell surface. It was suggested that urinary glycosaminoglycans might play some critical role in preventing crystal adhesion to these cellular membranes and that cell injuries might not be essential for the attachment of microcrystals to the tubular cells.

Animals↗

[Clinical study on antimicrobial prophylaxis following extracorporeal shock wave lithotripsy].

One hundred and sixty one patients with upper urinary stones were examined for antimicrobial prophylaxis following extracorporeal shock wave lithotripsy (ESWL). They were divided into two groups, the low-risk group (n = 133) and high-risk group (n = 28), according to the risk factors of urinary tract infection. The patients in the low-risk group were further randomized into two groups which were orally given ofloxacin for 7 days after ESWL (Group A, n = 66), no antimicrobial (Group B, n = 67). The patients in the high-risk group were randomly subdivided into three groups which were given flomoxef intravenously for 2 or 3 days and ofloxacin for 4 or 5 days thereafter (Group C, n = 10), flomoxef only for 2 or 3 days and no drugs later (Group D, n = 10), ofloxacin for 7 days (Group E, n = 8). In all of the patients in the low-risk group, during the 7 days after ESWL, fever elevation was observed in only 1.5% of patients, and bacteriuria in 10.0% on the 7th day. There was no difference in frequency of fever elevation and bacteriuria following ESWL between Group A and Group B. These findings indicate that prophylactic antimicrobial after ESWL treatment is not necessary for low risk patients with urinary tract infections. In the high-risk group, the over-all rates of fever elevation and bacteriuria were 21.4% and 24.0% respectively. The difference of effectiveness among the prophylactic regimens of the three groups (Group C, D, E) was not shown.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Specificity of chitosanase from Bacillus pumilus.

Partially (25-35%) N-acetylated chitosan was digested by chitosanase from Bacillus pumilus BN-262, and structures of the products, partially N-acetylated chitooligosaccharides, were analyzed in order to investigate the specificity of the chitosanase. The chitosanase produced glucosamine (GlcN) oligosaccharides abundantly, indicating that the chitosanase splits the beta-1,4-glycosidic linkage of GlcN-GlcN. The chitosanase also produced hetero-oligosaccharides consisting of glucosamine and N-acetyl-D-glucosamine (GlcNAc). Three types of the hetero-oligosaccharides purified by cation-exchange chromatography and HPLC were found to have GlcNAc residue at their reducing end and GlcN residue at their non-reducing end, indicating that the chitosanase can also split the linkage of GlcNAc-GlcN. The determination of the mode of action toward partially N-acetylated chitosan enables a classification of chitosanases according to their specificities and a more precise definition of chitosanases.

Bacillus↗