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Biomedical subjects

K Fujisawa

Publications and source records attributed to K Fujisawa.

At least 181 records · Page 10Linked to original sources
PubMed1993

Lysophosphatidic acid induces tyrosine phosphorylation and activation of MAP-kinase and focal adhesion kinase in cultured Swiss 3T3 cells.

Lysophosphatidic acid (LPA) added to serum-starved Swiss 3T3 cells induced, in a time- and concentration-dependent manner, tyrosine phosphorylation of multiple proteins, including proteins of 43, 64, 88 kDa and a group of proteins between 110 and 130 kDa. Among them, two proteins, p43 and p120, were identified as mitogen-activated protein kinase (MAP-kinase) and focal adhesion kinase (FAK), respectively, by immunoprecipitation and immunoblot analysis. Tyrosine phosphorylation of p64 peaked at 1 min and declined rapidly, whereas that of MAP-kinase and FAK peaked at 5 and 10 min after the addition of LPA, respectively. The activity of MAP-kinase determined as phosphorylation of myelin basic protein increased transiently about 3-fold at 5 min, and correlated with tyrosine phosphorylation. These results indicate that tyrosine phosphorylation of these proteins is a part of the signal transduction by LPA and may be involved in its mitogenic responses.

3T3 Cells↗
PubMed1993

The effect of therapy on platelet-associated autoantibody in chronic immune thrombocytopenic purpura.

Chronic immune thrombocytopenic purpura (ITP) is an autoimmune disorder due to autoantibody-induced destruction of platelets. Several forms of therapy have been used, including corticosteroids, splenectomy, danazol, and a variety of immunosuppressants. We studied the mechanism of action of some of these treatments by evaluating patients' platelet-associated autoantibodies (PAAb) and platelet count before and serially following therapy. Treatment with corticosteroids, splenectomy, cyclophosphamide, and combination chemotherapy resulted in a progressive decrease in PAAb associated with an improvement in the platelet count, and appeared to act by primarily affecting autoantibody production. Conversely, PAAb levels either remained stable or increased during vincristine or danazol therapy despite improvement in the platelet count, suggesting that the major effect of these agents was decreased platelet removal by the reticuloendothelial (RE) system.

Adrenal Cortex Hormones↗
PubMed1993

Platelet-associated antibody to glycoprotein IIb/IIIa from chronic immune thrombocytopenic purpura patients often binds to divalent cation-dependent antigens.

Chronic immune thrombocytopenic purpura (ITP) is a syndrome of destructive thrombocytopenia due to autoantibodies against platelet-associated antigens. These antigens are most commonly located on the platelet glycoprotein (GP) IIb/IIIa complex. In the present studies, we show that many platelet-associated anti-GPIIb/IIIa autoantibodies from chronic ITP patients depend on conformationally intact GPIIb/IIIa for maximal binding. We studied anti-GPIIb/IIIa autoantibodies from 19 ITP patients (15 platelet-associated, 8 plasma) and alloantibodies from three patients with posttransfusion purpura (anti-PIA1). Antibodies were preincubated with purified intact GPIIb/IIIa, EDTA-dissociated GPIIb/IIIa, GPIIIa, or GPIIb for 2 hours and then residual antibody was measured in an antigen capture assay. The binding results were compared with those obtained using antibody preincubated in buffer. Of the 15 platelet-associated autoantibodies studied, the intact GPIIb/IIIa complex resulted in greater inhibition of antibody binding than the EDTA-dissociated complex, with a mean inhibition ratio (intact/dissociated) of 7.9 (range, 1.4 to 30.3). Little inhibition was noted using either GPIIb or GPIIIa. Conversely, plasma anti-PIA1 alloantibodies or plasma autoantibodies from ITP patients against the c-terminal region of GPIIIa were more efficiently inhibited by the dissociated complex or purified GPIIIa. We conclude that platelet-associated anti-GPIIb/IIIa autoantibodies in chronic ITP are frequently directed to cation-dependent conformational antigens.

Autoantibodies↗
PubMed1993

Human seminal phosphatase. Properties and comparison with plant phosphatases.

1. Phosphatase activities were determined in various seminal fluid and plant tissues. 2. Human semen showed a markedly higher phosphatase activity, and some plants and mushrooms exhibited a considerably higher phosphatase activity. 3. Phosphatase purified from human seminal fluid showed a pH optimum of 5-6 and was potently inhibited by L-(+)-tartrate. 4. Tartrate could not inhibit most plant phosphatases, but inhibited the mushroom phosphatase with a one-order lower affinity than that of the seminal enzyme.

Basidiomycota↗
PubMed1993

Prediction of engraftment after peripheral blood stem cell transplantation by CD34-positive cells in grafts.

A total of 91 peripheral blood stem cell collections were performed in 26 children with various malignant tumors and peripheral blood stem cell transplantations (PBSCT) were performed in 15 of the children. There was a positive correlation between logarithm of total CD34+ cells/kg and logarithm of colony-forming unit-granulocyte macrophage (CFU-GM)/kg (r = 0.86). The time elapsed until the white blood cells (WBC) exceeded 1000/microL was related to both CFU-GM (r = 0.67) and CD34+ cell count (r = 0.60). The number of days elapsed until platelet count exceeded 5 x 10(4)/microL was not related to the logarithm of CFU-GM count/10(5) per kg transfused (r = 0.47), but was related to the logarithm of CD34+ cell counts/10(6) per kg transfused (r = 0.73). The number of days elapsed until the reticulocytes exceeded 10% was not related to the logarithm of CFU-GM count/10(5) per kg (r = 0.52), but was related to the logarithm of CD34+ cell counts/10(6) per kg transfused (r = 0.91). Although CD34+ cell counts correlated with the number of CFU-GM, bone marrow regeneration rates in three lineages were predicted more accurately by the number of CD34+ cells transfused than by the number of CFU-GM. These results suggest that measurement of the CD34+ cell count may be useful in predicting bone marrow regeneration rate after PBSCT.

Adolescent↗
PubMed1993

Importance of central nervous system involvement by neoplastic cells in a patient with Waldenström's macroglobulinemia developing neurologic abnormalities.

The clinicopathology of central nervous system (CNS) involvement with tumor formation in the brain of a patient with Waldenström's macroglobulinemia (WM) who developed neurologic abnormalities in the absence of blood hyperviscosity is reported. Extravascular infiltration by monoclonal lymphoplasmacytoid cells with considerable perivascular disruption of the brain and reactive gliosis was a conspicuous histopathologic picture. The tumor as well as the patient's neurologic symptoms were successfully controlled by local radiation to the brain. This case report illustrates the importance of CNS involvement by neoplastic cells in the differential diagnosis of a patient with WM developing neurologic abnormalities.

Aged↗
PubMed1993

Increased granulocyte/macrophage colony-stimulating factor production by mononuclear cells from peripheral blood of patients with bronchial asthma.

The in vitro production of granulocyte/macrophage colony-stimulating factor (GM-CSF) by mononuclear cells (MNC) from the peripheral blood of patients with bronchial asthma (BA) was examined by enzyme-linked immunosorbent assay (ELISA). GM-CSF concentrations in the media of MNC from patients with BA cultured with interleukin-2 (IL-2) was 80.2 +/- 52.0 pg/ml (mean +/- SE, n = 12), and that in cultures without a stimulant was 12.1 +/- 11.3 pg/ml. The GM-CSF concentrations in the media of MNC from patients with other diseases (n = 13) and from healthy volunteers (n = 6) cultured with or without IL-2 were less than 7.5 pg/ml (the minimum detectable value). The culture media of MNC from patients with BA demonstrated activities for stimulating the proliferation and survival of eosinophils, and these activities were partially inhibited by anti-GM-CSF antibodies. GM-CSF production by MNC of patients with BA treated with glucocorticoids was lower than that of MNC from untreated patients with BA, and it was inhibited by coculture with glucocorticoids in vitro. These results suggest that GM-CSF production by MNC is increased in patients with BA, is modulated by glucocorticoids, and may play an important role in the pathogenesis of BA.

Adult↗
PubMed1993

Factors that stimulate the proliferation and survival of eosinophils in eosinophilic pleural effusion: relationship to granulocyte/macrophage colony-stimulating factor, interleukin-5, and interleukin-3.

To investigate the mechanism of eosinophilia in patients with eosinophilic pleural effusions, we measured the activities of eosinophil colony-stimulating factor (Eo-CSF) and stimulating factor for eosinophil survival in the eosinophilic pleural fluids of six patients (two with tuberculous pleuritis, two with drug allergy, and one each with chronic eosinophilic pneumonia and pleuritis associated with rheumatoid arthritis). The number of eosinophil colonies formed by the pleural fluid of patients with eosinophilic pleural effusions significantly exceeded that of control patients with noneosinophilic pleural effusions (7.5 +/- 1.9 colonies/10(5) bone marrow cells, n = 6, versus 0.3 +/- 0.1 colonies/10(5) bone marrow cells, n = 6, P < 0.01). Similarly, eosinophil survival evaluated on day 4 of culture with pleural fluid of patients with eosinophilic pleural effusions significantly exceeded that of patients with noneosinophilic pleural effusions (83.9 +/- 9.8% versus 46.1 +/- 11.2%, P < 0.001). Both activities were inhibited mainly by anti-IL-5 antibody and partially by anti-GM-CSF antibody and anti-IL-3 antibody. Mononuclear cells obtained from eosinophilic pleural fluid released the activities of Eo-CSF and stimulating factor for eosinophil survival in vitro. These findings suggest that GM-CSF, IL-5, and IL-3 are important to eosinophil accumulation in pleural cavity as stimulators of proliferation and survival of eosinophils.

Adult↗
PubMed1993

Role of 830 nm low reactive level laser on the growth of an implanted glioma in mice.

The effect of low reactive level laser therapy (LLLT:830 nm, 60 mW, continuous wave) was studied using the model of a glioma implanted in mice. Two different models were used. In the first model, therapies were applied post the first day of glioma implantation; in the second model, post the fourteenth day of glioma implantation. Using the first model, therapies were designed as follows. 1) control group (no therapy), 2) direct LLLT (15 seconds twice per day; on the skin covering the implanted glioma), 3) indirect LLLT (15 seconds twice per day; on abdominal skin area rather than the site of the implanted glioma), 4) indirect LLLT (30 seconds twice per day), 5) anti-cancer drug (ACNU) group, 6) mouse beta-interferon (Mu-beta-IFN) group, 7) direct LLLT plus Mu-beta-IFN group, 8) ACNU plus Mu-beta-IFN group, 9) indirect LLLT (15 seconds twice per day) plus ACNU plus Mu-beta-IFN group. Using the second model, therapies were designed as follows. 1) control group (no therapy), 2) indirect LLLT (15 seconds twice per day), 3) indirect LLLT (15 seconds twice per day) plus Mu-beta-IFN group, 4) Mu-beta-IFN plus ACNU group. Our results indicated that, applied on the first day after glioma implantation, both direct and indirect LLLT were effective in inhibiting the tumor growth. In addition, it appeared that the effect of LLLT might be dose-dependent. Finally, the group of direct LLLT plus Mu-beta-IFN was most effective in limiting the tumor growth and the incidence of growth as compared with the other groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

[A neuropathological study on axonal dystrophy in the gracile nucleus of an old Japanese monkey].

Ageing axonal dystrophy was studied electron microscopically in the gracile nucleus of a very old Japanese monkey (28 years of age) from the standpoint of comparative neuropathology. It was revealed that the Japanese monkey has characteristics different from albino rats concerning the ultrastructure of the dystrophic axonal spheroids. Spheroids in the former animal contained no traces of so-called layered loops of membrane nor coiled tubular rings etc. which have been interpreted in cases of albino rats and other animal species as morphological expression of secondary metamorphosis of primarily accumulated normal axoplasmic organelles at the presynaptic boutons. Instead, spheroids in the Japanese monkey contained dense homogeneous osmiophilic granules and screwnail-like filament crystalloids, which have not been found in other animal species including albino rats. These abnormal substructures were already present in the early stage of axonal dystrophy and tended to occupy a large volumetric proportion of gigantic spheroids. It was concluded that these substructures constitute essential components of formed spheroids in combination with smooth axoplasmic reticulum, and that they represent primary products of axonal dystrophy and not the secondary products of metamorphosis like coiled tubular rings or layered loops of membrane described above. The enormous accumulation of smooth axoplasmic reticulum in other animal species including albino rats is characterized by the formation of a dense tridimensional reticular network. In the Japanese monkey, this process is characterized by massive dense parallel aggregation of straightened tubules of apparently smooth axoplasmic reticular origin rather than by formation of tridimensional network.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1993

Prevalence of hepatocellular carcinoma in patients with alcoholic cirrhosis and prior exposure to hepatitis C.

Sixty-three patients with alcoholic cirrhosis were retrospectively studied for the prevalence of antibodies to core (P22) and nonstructural (C100) region of hepatitis C virus (HCV). The prevalence rate of anti-P22 antibodies in patients with alcoholic cirrhosis was higher than that of anti-C100 antibodies (63.5% vs. 54.9%). The positivity rate of anti-C100 and/or anti-P22 antibodies was 73.0% (46/63) in alcoholic cirrhosis. We performed a multivariate analysis on the effects of age, sex, cumulative alcohol intake, anti-HCV antibodies, indocyanine green excretion test, and serum albumin on the development of hepatocellular carcinoma HCC in patients with cirrhosis, using Cox's proportional-hazards model, which revealed that anti-HCV positivity was the only independent prognostic variable for HCC in patients with alcoholic cirrhosis. The probability of HCC was significantly higher in the anti-HCV-positive patients than in the negative patients with alcoholic cirrhosis (p < 0.05). The 3-, 5- and 10-yr cumulative occurrence rate of HCC was, respectively, 13.3%, 41.3%, and 80.7% for anti-HCV-positive patients with alcoholic cirrhosis, compared with 0%, 8.3%, and 18.5% for anti-HCV-negative patients. In nonalcoholic patients with type C cirrhosis, the 3-, 5-, and 10-yr cumulative occurrence rate of HCC was 7.3%, 23.1%, and 56.5%, respectively. The follow-up studies indicate that hepatocarcinogenesis is hastened significantly in patients with alcoholic cirrhosis if they are positive for anti-HCV antibody, and that heavy alcohol consumption also is a risk factor for the development of HCC in patients with type C cirrhosis.

Adult↗
PubMed1993

[Neutrophil chemotactic factor in supernatant from pulmonary fibroblasts stimulated with cytokines].

Fibroblasts are important for maintenance of the structural frame network for most tissues, and they also play an important role in the inflammatory process via production of various mediators. In this study, we demonstrated that pulmonary fibroblasts may participate in pulmonary inflammation by production of neutrophil chemotactic factor (NCF). Pulmonary fibroblasts were stimulated with various cytokines (IGF-1, PDGF, IL-1 alpha, IL-1 beta, IL-2, IL-6, TNF, IFNr). Fibroblasts stimulated with either TNF, IL-1 alpha or IL-beta but not IGF, PDGF, IL-2 or IL-6 demonstrated a kinetic and dose-dependent increase in NCF activity. The NCF activity of crude supernatant was heat-stable and was not changed by anti-C5 antibody treatment or ether extraction. Characterization of the NCF activity by gel-filtration using high pressure liquid chromatography showed two active fractions, one with MW greater than 100 kD and the other with MW less than 10 kD. NCF activity in the small molecular weight fraction was demonstrated by inhibition of chemotaxis by addition of anti-IL-8 antibody. These data suggest that cytokine-treated fibroblast-derived NCF may be important in the pathogenesis and expression of a variety of pulmonary disease processes associated with neutrophil accumulation and activation.

Cytokines↗
PubMed1992

Different specificities of platelet-associated and plasma autoantibodies to platelet GPIIb-IIIa in patients with chronic immune thrombocytopenic purpura.

Chronic immune thrombocytopenic purpura (ITP) is an autoimmune disorder due to antiplatelet autoantibodies, many of which are directed against platelet membrane glycoprotein (GP) IIb-IIIa or GPIb-IX. In a recent study, we described plasma autoantibodies from 13 selected ITP patients, which required the presence of the putative GPIIIa cytoplasmic region for antibody binding. Since this region may not be available for antibody binding under physiologic conditions, we evaluated the frequency of binding to this or other regions of GPIIb-IIIa by platelet-associated and plasma autoantibody from a group of chronic ITP patients. We studied platelet-associated autoantibodies in 27 patients and plasma antibodies in 21 patients; in 15 patients, both were studied. To determine if autoantibodies were directed to the cytoplasmic portion of GPIIIa or to another portion of the GPIIb-IIIa molecule, antibody eluted from patient platelets or plasma antibody was tested in an antigen capture assay for binding to GPIIb-IIIa obtained from Chinese hamster ovary (CHO) cells transfected with GPIIb and either intact GPIIIa or GPIIIa lacking the carboxy terminal 35 residues. Of the 21 plasma autoantibodies tested, 13 bound primarily to the carboxy terminus of GPIIIa and eight to other epitopes. Conversely, all 26 platelet-associated autoantibodies, including eight of the 13 with anti-carboxy terminus antibodies, bound to epitopes in other regions of GPIIb-IIIa. Comparison of the degree of antibody adsorption by intact or lysed platelets indicated that epitopes on the c-terminal region of GPIIIa are relatively inaccessible on the surface of intact washed platelets when compared with other epitopes. We conclude that the importance of plasma autoantibodies in chronic ITP patients should be interpreted cautiously, since their specificity may differ from that of antibodies bound to the platelet. Whether antibodies against the c-terminus of GPIIIa are of pathogenetic importance remains to be determined, although patients with these antibodies have particularly severe disease.

Animals↗
PubMed1992

A visual field quantification system for the Goldmann Perimeter.

We have developed a visual field quantification system that can accurately quantify the measurement results by the Goldmann Perimeter (GP). This system calculates the plural indexes introduced in published papers. In recent years, several isopter quantification methods have been proposed. In these methods, the isopters are digitized and the data are input into a computer, after which a computer program evaluates the changes in the isopters quantitatively. However, each program is only able to evaluate private indexes. We have developed a system that quantifies data using multiple methods. This system used five methods that have been introduced in published papers. With this system, a physician can analyze GP data with multiple methods and can diagnose diseases accurately. We have already input about 2500 GP recording papers into the computer by this system. We then calculated the plural indexes, and visualized the temporal changes in the perimetry.

Humans↗
PubMed1992

Hemoglobin Kansas found in a patient with polycythemia.

A 62-year-old woman, long suspected of having heart disease, was admitted to our hospital for thorough examination. Her hemoglobin level was 17.7 g/dl and her 2.3-DPG level was 8.90 microM/ml RBC. The patient proved to have polycythemia, hemoglobin Kansas, and diabetes mellitus. To our knowledge, this is the third case of hemoglobin Kansas in the world.

2,3-Diphosphoglycerate↗
PubMed1992

Establishment and characteristics of a T-cell acute lymphoblastic leukemia cell line, JK-T1, with a chromosomal translocation between 8q24 and 14q13.

A human leukemia cell line, JK-T1, was established from the bone marrow of a 10-year-old boy with T-cell acute lymphoblastic leukemia. The origin of the leukemic cell line, JK-T1, was demonstrated by its chromosomal and immunologic similarity to the patient's fresh leukemic cells. Karyotypic analysis revealed 46,XY,del(6)(q?),t(8;14)(q24;q13),der(9)t(9;?)(q34;?). In JK-T1, neither rearrangement nor amplification of the c-myc gene was observed apparently because the breakpoint of chromosome 14 was not q11 but q13. JK-T1 was independent of interleukin 2 (IL-2) because of little production of IL-2, little IL-2 receptor (CD25) on the surface, and no response to exogenous IL-2. JK-T1 had lymphocyte function associated antigen-1 (LFA-1) (CD11a, CD18) on its surface and could adhere to the hematologic stromal layer. These characteristics of JK-T1 cell line are considered to be useful not only for evaluating the role of t(8;14) but also in studying the adhesion molecules of leukemia.

Bone Marrow Cells↗
PubMed1992

Genomic characterization and mutation rate of hepatitis C virus isolated from a patient who contracted hepatitis during an epidemic of non-A, non-B hepatitis in Japan.

To investigate the genomic characterization of hepatitis C virus (HCV) isolated from patient who contracted hepatitis during an epidemic of non-A, non-B (NANB) hepatitis in Shimizu city, Japan, we have cloned the nucleotide sequence of the viral genome (HCV-KF) spanning the structural domain. When compared to other previously reported HCV isolates, HCV-KF showed an overall identity at the amino acid level of 90.0 to 92.1% with Japanese isolates and 80.9 to 82.1% with American-like isolates. The HCV-KF genome displays an insertion of three nucleotides in-frame (corresponding to one amino acid) found at the junction between the E1 and E2/NS1 region. The mutation rate of the HCV-KF genome was assessed by comparing the nucleotide and deduced amino acid sequences of the viral RNA obtained from the serum of the original patient with viral sequences derived from the serum of a chimpanzee inoculated with the same serum 9 years previously. The substitution rate of the viral genome was estimated at 0.9 x 10(-3) nucleotides per site per year for the HCV structural region. The highest mutation rate was found in the hypervariable region within the E2/NS1 domain. It is suggested that the outbreak in Shimizu city was caused by a strain of HCV closely related to the Japanese-like subgroup of isolates.

Americas↗