PubMed Health⌕ Search

Biomedical subjects

K Ohkawa

Publications and source records attributed to K Ohkawa.

At least 91 records · Page 5Linked to original sources
PubMed1994

IgG and IgM core antibodies and viral replication in hepatitis C virus carriers.

We studied IgG and IgM antibodies to hepatitis C virus core protein (anti-HCVcore) in relation to serum virus RNA levels in 71 hepatitis C virus carriers. Viremic levels ranged from 10(4)-10(9) copies/ml and were high in 34 chronic active hepatitis patients compared with 17 asymptomatic carriers and 20 cases of chronic persistent hepatitis (p < 0.01). IgG anti-HCVcore was found in 67/71 (94%), but four asymptomatic carriers with low levels of viremia (10(4)-10(5.5) copies/ml) tested negative. IgM anti-HCVcore was found in patients with high levels of viremia (10(8)-10(9) copies/ml), and one (6%) asymptomatic carrier and nine (26%) chronic active hepatitis patients tested positive. In chronic hepatitis patients, viremic levels were significantly higher in cases positive for IgM anti-HCVcore than in negative ones (p < 0.01). However, no correlation was found between the occurrence of IgM anti-HCVcore and serum aminotransferase levels or the histologic activity index. These findings suggest that although IgG anti-HCVcore is sensitive, low viremic patients can escape this screening, and that the IgM anti-HCVcore is induced in association with high levels of virus replication.

Adult↗
PubMed1994

Hepatitis C virus antibodies and virus replication in asymptomatic blood donors.

We assessed hepatitis C virus (HCV) infection in 99 asymptomatic blood donors positive using a first-generation HCV antibody assay. When tested with second-generation assays, 86 (87%) donors were reactive (group 1), 2 (2%) were indeterminate (group 2), and 11 (11%) were non-reactive (group 3). Viraemia was revealed by polymerase chain reaction in all group 1 cases. The 2 group 2 cases and 6 (55%) group 3 cases were also viraemic. Viraemia was confirmed by a branched DNA assay in the 2 group 2 cases and 4 (36%) group 3 cases. Serum HCV RNA levels were further studied using a competitive reverse transcription-polymerase chain reaction assay. All cases in groups 2 and 3 were low viraemic (range 10(4)-10(5.5) copies/ml) compared with the 9 group 1 cases examined (range 10(7)-10(9) copies/ml). No correlation was evident between viraemic levels and antibody cut-off index in the first-generation assay. These findings indicate the possibility that low levels of viraemia can occur in individuals non-reactive in second-generation HCV antibody assays.

Adult↗
PubMed1994

Hepatitis C virus replication and antibody responses toward specific hepatitis C virus proteins.

We assessed the correlation between hepatitis C virus replication and antibody responses toward hepatitis C virus core (C22-3), NS3 (C33C), NS4 (5-1-1 and C100-3) and NS5 proteins in 59 virus carriers. The concentration of serum hepatitis C virus RNA was determined by a competitive reverse transcription-polymerase chain reaction assay. All 50 patients with high viremic levels of > or = 10(6) copies/mL had antibodies to C22-3 and C33C. Antibodies to 5-1-1, C100-3 and NS5 proteins were detected less frequently (p < 0.01) in 72% (36 of 50), 78% (39 of 50) and 84% (32 of 38) of such patients, respectively. As for the nine patients with low viremic levels of < 10(6) copies/mL, antibodies to C22-3, C33C, 5-1-1 and NS5 proteins were detected in only one patient (11%), which was significantly less than the frequency for highly viremic patients (p < 0.01). Antibody to C100-3 was also found less frequently in only four patients (44%) (p < 0.05). Thus, only four (44%) of the nine low viremic patients tested positive for any antibody compared with all 50 highly viremic patients (p < 0.01). These results indicate that highly viremic carriers can be detected by the presence of hepatitis C virus antibodies, but a considerable proportion of low viremic carriers may not show any serological evidence of hepatitis C virus infection.

Adult↗
PubMed1993

Bovine serum albumin-doxorubicin conjugate overcomes multidrug resistance in a rat hepatoma.

A bovine serum albumin-conjugated doxorubicin via the glutaraldehyde bridge (BSA-DXR conjugate) showed potent dose-dependent inhibition of cell growth against daunorubicin-resistant AH66 (AH66DR) cells as well as parental AH66 (AH66P) cells in vitro as compared to treatment with DXR or BSA-glutaraldehyde conjugate without DXR (BSA-GA). In the culture of AH66DR with BSA-DXR conjugate, drug accumulation in the AH66DR cells increased as a function of time up to 24 h reaching approximately the same drug level as AH66P cells treated with DXR. The intracellular accumulation of the BSA-DXR conjugate was inhibited by the addition of ammonium chloride, while that of DXR alone was not inhibited. Intracellular DXR was effluxed rapidly from AH66DR cells, but BSA-DXR conjugate or pharmacologically active DXR adduct remained in the cells at a relatively high concentration over a 36-h time period. The life-prolonging effect of the conjugate was assessed using rats inoculated i.p. with AH66P or AH66DR. The rats were treated with the BSA-DXR conjugate, DXR, a mixture of DXR with BSA, or BSA-GA by either the i.p. or i.v. route. Treatment with DXR had no significant surviving effect as compared to that with saline in AH66P-bearing rats. By contrast, BSA-DXR conjugate showed a significant life-prolonging effect as compared with DXR alone in the same degree both in AH66P- and AH66DR-bearing rats. BSA-GA did not show any toxicity in vivo as well as in vitro. These results indicate that the BSA-DXR conjugate allows DXR to escape from the multidrug resistance mechanism.

Animals↗
PubMed1993

Effect of saiboku-to (TJ-96) on bronchial asthma. Induction of glucocorticoid receptor, beta-adrenaline receptor, IgE-Fc epsilon receptor expression and its effect on experimental immediate and late asthmatic reaction.

A remarkable "steroid sparing" effect of Saiboku-to was noted within 6 to 12 months of treatment in steroid-dependent asthmatic patients. Saiboku-to spared the downregulation of glucocorticoid receptor of human lymphocytes, plasma ACTH, and cortisol levels. It also spared downregulation of beta 2 receptor by beta 2 agonists and suppressed mACh receptor at the same time. Saiboku-to increased tyrosine aminotransferase (TAT) production, which was inhibited by actinomycin-D, thus having steroid-like activity. In mite-allergic asthma, Saiboku-to inhibited the induction of expression of IgE-Fc epsilon R/CD23 in the lymphocytes by mite allergen. It also inhibited IgE production by mite allergens. In experimental asthma in guinea pigs the use of Saiboku-to resulted in a decrease in the number of eosinophils in the bronchoalveolar lavage fluid during late asthmatic response. These findings suggest that Saiboku-to may be effective in inhibiting both the expression of IgE-Fc epsilon R2 and the induction of expression of IgE-Fc epsilon R1. Saiboku-to also has a steroid-like action and polyhedral anti-asthmatic activities.

Animals↗
PubMed1993

Inhibitory effect of nonenzymatic glycation on ubiquitination and ubiquitin-mediated degradation of lysozyme.

We examined ubiquitination and ubiquitin-mediated degradation of glycated protein by rabbit reticulocyte lysate fraction II (ubiquitin-free preparation). Non-glycated lysozyme and three glycated lysozyme preparations with different glucose binding ratios were used as substrates. Glycation sites of the lysozyme were mostly the epsilon-NH2 group of lysine residues, since modification at the alpha-NH2 group of the amino terminal was not detectable. Ubiquitin was conjugated with three glycated lysozyme preparations, which contained 1.4, 2.8 and 4.5 mol glucose per mol, by fraction II supplemented with hemin. The extent of formed conjugates was reduced 81, 72 and 56% of those of ubiquitin-non-glycated lysozyme conjugates, respectively. Additionally, ubiquitin-mediated degradation of the resultant conjugates was reduced and their respective rates were 97, 56 and 19% of that of the non-glycated lysozyme. These results indicated that both ubiquitin conjugation and ubiquitin-mediated degradation of the lysozyme were inhibited by nonenzymatic glucose binding to the lysozyme.

Electrophoresis, Polyacrylamide Gel↗
PubMed1993

Purification and properties of pyridoxal kinase from bovine brain.

A 27,000-fold purification of pyridoxal kinase from bovine brain tissue has been achieved by a combination of ammonium sulfate fractionation, DEAE-cellulose chromatography, hydroxyapatite chromatography, Sephadex G-150 gel filtration, Blue Sepharose CL-6B chromatography, and Phenyl-Superose chromatography. The final chromatography step yields a homogeneous preparation of high specific activity (2105 nmol/min/mg protein). The molecular mass of the native enzyme was estimated to be approximately 80,000 on gel filtration. The subunit molecular mass was determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis to be approximately 39,500. This indicates that pyridoxal kinase is a dimeric enzyme.

Animals↗
PubMed1993

Inversion of chromosome 16 and eosinophilia in refractory anemia with ring sideroblasts: report of a case.

A 72-year-old male who was admitted to our hospital with severe anemia was diagnosed as refractory anemia with ring sideroblasts (RARS), according to the French-American-British (FAB) classification of myelodysplastic syndromes (MDS). The patient showed persistent eosinophilia with no definite signs of either allergy or a parasitic infection. Chromosomal analysis of bone marrow cells revealed inv(16)(p13q22), a known characteristic of M4Eo acute myeloid leukemia (AML) in the FAB classification. This patient didn't exhibit leukemic transformation during his 20-month clinical course, nor was any found at autopsy. Therefore, this is the first case of RARS to speculate that the chromosomal characteristic inv(16)(p13q22) might be specific for eosinophilia rather than AML.

Aged↗
PubMed1993

Chemotherapeutic efficacy of the protein-doxorubicin conjugates on multidrug resistant rat hepatoma cell line in vitro.

In vitro studies were initiated to study the antitumour effect of protein-doxorubicin (DXR) conjugate on the growth of the multidrug resistant rat ascites hepatoma cell line, AH66DR. The 50% inhibitory concentration (IC50) for DXR in AH66DR cell line was 16 mumol l-1 (AH66 parental cell line, AH66P, IC50 was 0.08 mumol l-1). Treatment of AH66P and AH66DR cells with various concentrations of DXR or conjugates at equivalent concentrations of DXR was performed. The two types of conjugates used were bovine serum albumin (BSA)-DXR conjugate and immunoglobulin G (IgG)-DXR conjugate. Both of these conjugates showed potent dose-dependent inhibition of cell growth against AH66DR cells as compared with the cells treated with DXR or other controls. The IC50 for BSA-DXR and IgG-DXR conjugates in AH66DR cell line was 0.05 (equivalent DXR) mumol l-1 and 0.07 (equivalent DXR) mumol l-1, respectively. These values were similar to that of the AH66P treated with DXR. Cellular uptake and accumulation of DXR or BSA-DXR conjugate was also quantitated in both cell lines. The cellular concentration of DXR in AH66DR cells was 2-fold lower than that of AH66P cells throughout the experiment. In contrast, by the treatment of AH66DR cells with BSA-DXR conjugate, the intracellular drug concentration increased as a function of time up to 24 h (639.1 +/- 41.8, equivalent DXR, ng 10(-5) cells) and reached the same drug level as AH66P cells treated with DXR (617.9 +/- 17.3 ng-5 cells). Ammonium chloride treatment inhibited the effects of the conjugates but did not inhibit the free drugs. Intracellular DXR was effluxed rapidly from AH66DR cells, but BSA-DXR conjugate remained in the cells at relatively high concentration for a long time. These results indicate that by chemically modifying DXR, such as by conjugation of the drug with proteins, it may be possible to overcome multidrug resistance.

Animals↗
PubMed1993

Recombinant human granulocyte colony-stimulating factor in combination with continuous infusion of cytosine arabinoside for the treatment of refractory acute myelogenous leukemia.

Because recombinant human granulocyte colony-stimulating factor (G-CSF) has been reported to increase the sensitivity of acute myelogenous leukemia (AML) blast cells to cytosine arabinoside (Ara-C) in vitro, we treated a patient with refractory AML with an Ara-C-based regimen in combination with G-CSF (G-CSF/Ara-C therapy). G-CSF (50 micrograms/m2/day, subcutaneous injection) was administered simultaneously with a continuous intravenous infusion of Ara-C (70 mg/m2/day). Complete remission was achieved, however, severe neutropenia, documented infection, stomatitis, and diarrhea were observed. In vitro studies using 3H-thymidine uptake and dual parameter flow-cytometric analysis of DNA and proliferating cell nuclear antigen showed that leukemic blast cells in S phase were increased after incubation with G-CSF. G-CSF also enhanced expression of the transferrin receptor (CD71) on blast cells in vitro. These observations suggest that G-CSF/Ara-C therapy may be useful in the treatment of high-risk AML.

Bone Marrow↗
PubMed1993

Cytotoxic effect of the protein-doxorubicin conjugates on the multidrug-resistant human myelogenous leukemia cell line, K562, in vitro.

In vitro studies were performed to examine the antitumor effect of protein-doxorubicin (DXR) conjugate on the growth of the multidrug-resistant human chronic myelogenous leukemia cell line, K562/DXR. The 50% inhibitory concentration (IC50) for DXR in the K562/DXR cell line was 20 nM (in the K562 parental cell line, IC50 was 3.2 nM). Treatment of both types of cells with various concentrations of DXR or conjugates at equivalent concentrations of DXR was carried out. One type of the conjugates used was human serum albumin (HSA)-DXR conjugate and human transferrin (Tf)-DXR conjugate via a glutaraldehyde bridge (HSA-ga-DXR, Tf-ga-DXR, respectively) and another type used was HSA-DXR conjugate with a dextran bridge (HSA-dex-DXR). All of these conjugates showed potent dose-dependent inhibition of cell growth against the K562/DXR cells as compared with the cells treated with DXR or other controls. IC50 for HSA-ga-DXR, Tf-ga-DXR and HSA-dex-DXR conjugates in the K562/DXR cell line was 2.4, 3.6 and 1.0 (equivalent DXR) nM, respectively, which were approximately similar to the value of the K562 treated with DXR. Through the treatment of K562/DXR cells with HSA-DXR conjugate, the intracellular drug concentration increased as a function of time up to 24 h compared with the cells treated with DXR. Intracellular DXR effluxed rapidly from K562/DXR cells, but HSA-ga-DXR as well as HSA-dex-DXR conjugates remained in the cells at a relatively high concentration for a long time. These results indicate that it may be possible to overcome multidrug resistance by chemically modifying DXR, such as by conjugation of the drug with proteins.

Cell Survival↗
PubMed1992

Growth of a human yolk sac tumor cell line with yolk sac-derived functions in selenium-supplemented chemically defined synthetic medium.

A human yolk sac tumor cell line, TG1, which was established from a testicular yolk sac tumor, was found to replicate continuously in a chemically defined medium supplemented with Na2SeO3 (ISRPMI). TG1 produced several plasma proteins and growth factors: albumin, alpha-fetoprotein (AFP), ferritin, carcinoembryonic antigen, beta-2-microglobulin, polyamine, neuron specific enolase, tissue polypeptide antigen, transferrin (Tf), epidermal growth factor, and platelet derived growth factor. By analysis of lentil lectin (LcHA)-affinity electrophoresis, to examine the microheterogeneity of carbohydrate chains of synthetic glycoproteins, TG1 cells cultured with ISRPMI produced only LcHA reactive Tf and AFP based on core fucose attached to asparagine-linked N-acetylglucosamine residues instead of LcHA-nonreactive Tf and AFP produced by TG1 cells cultured with fetal bovine serum (FBS)-containing medium. alpha 1-6 Fucosyltransferase activity was significantly greater in the TG1 cells cultured with ISRPMI (39.9 +/- 1.5 pmol.h-1.mg-1 protein) than cultured with FBS-containing media (18.2 +/- 1.2 pmol.h-1.mg-1 protein). These results have indicated that the selective increase of alpha 1-6 fucosyltransferase occurred when the cells were cultured with the FBS-free synthetic media.

Carcinoembryonic Antigen↗
PubMed1992

Effects of interleukin-3 and interleukin-6 on peripheral blood cells from multiple myeloma patients and their clinical significance.

The effects of interleukin-3 (IL-3) and interleukin-6 (IL-6) on nonadherent mononuclear cells (NMC) from the peripheral blood of 28 patients with multiple myeloma (MM), 3 patients with monoclonal gammopathy of undetermined significance (MGUS), and 3 normal controls were investigated. In 15 of 27 evaluable patients with MM, monoclonal-cytoplasmic-immunoglobulin (cIg)-positive plasma cells appeared from the T-cell-depleted NMC after 10 days of culture in the presence of IL-3 and IL-6. These changes were not observed in the T cell fraction of myeloma blood or in the T-cell-depleted NMC obtained from cases of MGUS or from normal controls. The percentage of cIg-positive plasmacytoid cells after 10 days of culture was significantly higher in the presence of both IL-3 and IL-6 than with each interleukin alone or the control medium. Furthermore, these changes were often observed in untreated patients. These findings suggest that myeloma precursor cells exist in the peripheral blood of MM patients, especially at diagnosis, and differentiate into cIg-positive cells in the presence of IL-3 and IL-6. This assay may be useful in discriminating the early stage of myeloma from MGUS.

Antigens, CD↗
PubMed1992

[Auer rods-positive neutrophils observed at diagnosis increased after remission induction in patient with acute promyelocytic leukemia].

50-year-old male was admitted to our hospital because of gingival bleeding and fever in August 1987. The leukocyte count was 13,300/microliters with 80.5% leukemic promyelocytes and bone marrow was hypercellular with 86.4% leukemic promyelocytes. A small number of mature neutrophils containing Auer rods were seen in bone marrow. On a diagnosis of acute promyelocytic leukemia and treated with induction chemotherapy consisting of behenoyl-arabinofuranosyl cytosine (BHAC), daunorubicin, 6-mercaptopurine (6-MP) and prednisolone (PSL) was reformed. After cytoreduction, leukemic cells reappeared in the peripheral blood, concomitant with mature neutrophils having Auer rods. Vitamin D3 was not effective as a differentiation inducing agent. Complete remission was obtained in November 1987 by the reinduction chemotherapy consisting of BHAC, aclarubicin, 6-MP and PSL. In this case, neutrophils with Auer rods might have been derived from the leukemic clone and differentiation of leukemic promyelocytes by intensive chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

An evaluation of ovarian carcinoma-associated antigen defined by murine monoclonal antibody CF511 in sera from patients with ovarian carcinoma.

Murine monoclonal antibody CF511, raised against human ovarian clear cell carcinoma, detects a glycoprotein (Mr 600 kDa) called CF511 antigen which is elevated in the serum of many patients with ovarian carcinoma. A competitive enzyme-linked immunosorbent assay was developed to detect CF511 antigen in human serum and used to detected CF511 antigen in subjects with ovarian carcinoma and other diseases. No raised levels (less than 18 unit (U) ml-1) of the antigen were found in the serum of 220 normal individuals or of patients with germ cell tumours (n = 6), granulosa theca cell tumour (n = 1), gastric carcinomas (n = 10) and colo-rectal carcinomas (n = 8). Raised serum levels of CF511 antigen were found in 6/46 patients (13.0%) with benign gynaecological tumours (including endometriosis or ovarian cyst), in 5/7 patients (71.4%) with breast carcinoma and 16/21 (76.2%) lung carcinoma patients. In patients with ovarian carcinoma, 42.3% (11/26) of stage I and II, and 96.0% (24/25) of stage III and IV had levels of greater than or equal to 18 U ml-1. In all patients with serial determination of CF511 antigen levels before and after the surgery, the levels of antigen correlated with the clinical course of disease. Determination of CF511 antigen levels may be useful for detection of ovarian carcinoma as well as lung and breast carcinomas and for monitoring progress of disease and response to therapy.

Antibodies, Monoclonal↗