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Biomedical subjects

D Hata

Publications and source records attributed to D Hata.

32 records · Page 2Linked to original sources
PubMed1993

Cyclosporin A and FK506 block the negative signaling mediated by surface IgM cross-linking in normal human mature B cells.

Cross-linking of surface IgM (sIgM) or sIgD by anti-IgM Ab or anti-IgD Ab, respectively, induced DNA synthesis in peripheral blood B cells (PBL-B). Cell division, determined by the increase in the number of M phase cells, was also induced when PBL-B were stimulated with anti-IgD Ab plus IL-4 or Staphylococcus aureus Cowan I (SAC), but far less by stimulation with anti-IgM Ab plus IL-4. Anti-IgM Ab did not suppress the DNA synthesis induced by SAC or anti-IgD Ab plus IL-4, but it did suppress the cell division induced by them. Thus, sIgM cross-linking generates both positive and negative signaling to B-cell proliferation. Cyclosporin A (CSA) and FK506 suppressed DNA synthesis and cell division at relatively high concentrations. On the other hand, CSA and FK506 at lower concentrations blocked the anti-IgM Ab-generated inhibition of cell division without affecting DNA synthesis. Low concentrations of CSA did not affect the cell division induced by anti-IgD Ab plus IL-4 but did increase the cell division induced by SAC or anti-IgM Ab plus IL-4, suggesting that stimulation with SAC, as well as with anti-IgM Ab plus IL-4, generates both positive and negative signals to cell division, whereas sIgD lacks the ability to transduce negative signaling.

Antibodies, Anti-Idiotypic↗
PubMed1992

Tyrosine phosphorylation and its possible role in superoxide production by human neutrophils stimulated with FMLP and IgG.

Superoxide production by human neutrophils stimulated with FMLP and soluble aggregated human IgG were inhibited in a dose dependent manner by two kinds of tyrosine kinase inhibitors, erbstatin and genistein. Superoxide production stimulated with surface bound IgG, however, was scarcely inhibited by either inhibitor. Protein tyrosine phosphorylation studies with immunoblotting revealed specific tyrosine phosphorylation of a 40 Kd protein by soluble aggregated and surface bound IgG, and that of a 39 Kd protein, as well as the 40 Kd protein, by FMLP. These were all inhibited by the tyrosine kinase inhibitors. These data suggest that superoxide production induced by FMLP and soluble aggregated IgG are, at least in part, tyrosine kinase dependent, but the tyrosine kinases and/or substrates of tyrosine kinases involved may be different. In addition, tyrosine kinase independent pathways are also suggested to be involved in superoxide production by stimulation with surface bound IgG.

Humans↗
PubMed1992

Regulation of cell division of mature B cells by ionomycin and phorbol ester.

The growth of a human B lymphoma cell line B104, an experimental model for mature B cells, was inhibited by ionomycin but not 12-O-tetradecanoylphorbol-13-acetate (TPA). Ionomycin inhibited B104 cells from entering into the M phase of the cell cycle without affecting DNA synthesis. The inhibition of cell division of B104 cells by ionomycin occurred within 24 h after stimulation. Because such a mode of action resembles that of anti-IgM antibodies, signals transduced by Ca2+ may be responsible for the inhibition of cell division of B104 cells by anti-IgM antibodies. Indeed, EGTA suppressed the inhibition of cell division of B104 cells caused not only by ionomycin, but also by anti-IgM antibody. Although TPA itself did not have any ability to promote the growth of B104 cells, it could cancel the inhibition of cell division of B104 cells by ionomycin and increase the proportion of B104 cells entering into the M phase of the cell cycle. Staphylococcus aureus Cowan I causes the greatest proliferation of normal human peripheral blood B cells during the period from 48 to 72 h after stimulation. When ionomycin was added to S. aureus Cowan I-stimulated peripheral blood B cells at 48 h of culture, it inhibited cell division during this period without affecting DNA synthesis. In the presence of TPA, this activity of ionomycin was suppressed, and the proportion of M-phase cells increased. These results suggest that cell division of mature B cells is regulated by the signals mediated by Ca2+ and protein kinase C in a mode quite different from that of regulation of DNA synthesis.

B-Lymphocytes↗
PubMed1992

Anti-IgM antibody-induced cell death in a human B lymphoma cell line, B104, represents a novel programmed cell death.

We investigated the mechanisms of anti-IgM antibody-induced cell death in a recently established human surface IgM+ IgD+ B lymphoma cell line, B104, the growth of which is irreversibly inhibited by anti-IgM antibody but not by anti-IgD antibody, and compared it with the cell death of T cells via TCR/CD3 complex and with the cell death of a murine anti-IgM antibody-sensitive B lymphoma cell line, WEHI-231. The rapid time course of B104 cell death and its requirements for de novo macromolecular synthesis and Ca2+ influx suggest that anti-IgM antibody-induced B104 cell death is an active Ca(2+)-dependent programmed cell death. Moreover, cyclosporin A rescued B104 cells from this lethal signal, via surface IgM, suggesting that the intracellular mechanisms involved are quite similar to those of T cell death. DNA fragmentation, which has been reported in TCR/CD3 complex-mediated T cell death, apoptosis, was not involved in the B104 cell death process, but the possible involvement of DNA single-strand breaks was suggested. Observations under light microscopy and transmission electron microscopy indicated that the morphologic features of dying B104 cells resembled necrosis rather than apoptosis. B104 cell death was shown to be quite distinct from that of WEHI-231 in cell death kinetics, the mode of cell death, and the response to cyclosporin A. These data collectively indicate that the death of B104 cells resulting from surface IgM cross-linking represents a hitherto undefined mode of programmed cell death.

Antibodies, Anti-Idiotypic↗
PubMed1992

Anti-IgM but not anti-IgD antibodies inhibit cell division of normal human mature B cells.

Insolubilized anti-IgD antibody markedly increased DNA synthesis in and cell division of normal peripheral blood B cells (PBL-B) when used in combination with IL-4. Anti-IgM antibodies also induced DNA synthesis of PBL-B, but their ability to induce cell division was less than that of anti-IgD antibodies even when used in combination with IL-4. Moreover, anti-IgM antibodies inhibited cell division of PBL-B stimulated with insolubilized anti-IgD antibody plus IL-4 without affecting DNA synthesis. Anti-IgM antibodies also inhibited Staphylococcus aureus Cowan I-induced cell division of PBL-B without affecting DNA synthesis. These results indicate that cross-linkage of surface IgM (sIgM) in mature B cells generates negative signals to inhibit cell division of mature B cells. Because anti-IgD antibodies did not inhibit cell division at all, the role of sIgD in the regulation of cell division of mature B cells may be quite different from that of sIgM. IFN-alpha/beta promoted cell division of PBL-B stimulated with insolubilized anti-IgD antibody plus IL-4. They also counteracted the inhibitory effect of anti-IgM antibody on cell division of PBL-B.

Antibodies, Anti-Idiotypic↗
PubMed1992

Tyrosine phosphorylation of IgM- and IgD-associated molecules of a human B lymphoma cell line B104.

We investigated tyrosine phosphorylation and structural properties of the IgM-associated molecules in comparison with IgD-associated molecules in a recently established human surface IgM+, IgD+ B lymphoma cell line, B104, the growth of which was irreversibly inhibited by anti-IgM mAbs but not by anti-IgD mAbs. Tyrosine kinase activity and tyrosine phosphorylated proteins were detected in anti-IgM and anti-IgD immunoprecipitates from digitonin lysates of B104 cells with the use of an in vitro kinase assay followed by a re-immunoprecipitation experiment with anti-phosphotyrosine mAbs. Tyrosine phosphorylated proteins of 74, 58-44, 41, and 39 kDa were detected in anti-IgM immunoprecipitates, whereas tyrosine phosphorylated proteins of 74, 58-44, and 39 kDa, but not 41 kDa, were detected in anti-IgD immunoprecipitates. Crosslinking of surface IgM and surface IgD stimulated rapid tyrosine phosphorylation of different sets of proteins which included tyrosine-phosphorylated proteins of the same or similar molecular weights as those detected in the anti-IgM and anti-IgD immunoprecipitates respectively. After deglycosylation by N-glycosidase, both the IgM- and IgD-associated phosphoproteins (pp58-pp39) gave rise to the same three bands of 29, 27, and 26 kDa. Proteolytic peptide mapping of these three deglycosylated proteins showed that the primary structures of the IgM- and IgD-associated molecules are identical, suggesting that the IgM- and IgD-associated phosphoproteins (pp58-pp39) are the products of the same or closely related genes. One of the products, pp41, may be associated with IgM, but not with IgD, although the same gene product may be associated with IgD in a different glycosylation pattern.

Antibodies, Anti-Idiotypic↗
PubMed1992

[Clinical evaluation of cefprozil in children].

Cefprozil (CFPZ, BMY-28100), a new oral cephalosporin, was evaluated for its efficacy and safety in 42 children with bacterial infections (Table 1), and the following results were obtained. 1. CFPZ was administered in 3 or 4 divided doses at daily dosages ranging from 15.3 to 60.0 mg/kg to 42 patients (19 cases of acute tonsillitis and/or laryngitis, pharyngitis, 13 cases of pneumonia, 2 cases each of suppurative cervical lymphadenitis and UTI, and 1 case each of scarlet fever, acute otitis media, suppurative parotitis, impetigo contagiosa, furuncle and acute enteritis) and the following clinical results were obtained: excellent; 24 cases, good; 14 cases, fair; 4 cases. The overall efficacy rate was 90.5% (Table 3). 2. MICs of CFPZ against 50 strains of isolated organisms are shown in Table 4. In 19 cases out of 28 cases examined, causative organisms were successfully eradicated and strain of Staphylococcus aureus was decreased in 1 case. 3. Diarrhea was observed in 2 cases (cases 8, 11). In case 8, the symptom disappeared spontaneously. Case 11 improved immediately after the administration of the drug was stopped. Among 39 children who went through laboratory tests, eosinophilia which seemed to be related to the administration of this drug was observed in 2 cases (cases 29, 38). Slight elevations of S-GOT and S-GPT were found in 1 case (case 22) (Table 7). 4. These data suggest that CFPZ is a safe and useful new antibiotic in the treatment of children with susceptible bacterial infections.

Administration, Oral↗
PubMed1991

Growth regulation of a human mature B cell line, B104, by anti-IgM and anti-IgD antibodies.

An EBNA- human B lymphoma cell line, B104, was established. B104 cells express IgD as well as IgM on their surface, which is thought to be a basic characteristic of mature B cells. The growth of B104 cells was inhibited by treatment with a panel of anti-IgM antibodies. Cell cycle analyses revealed that the transition of B104 cells from the G2/M to the G0/G1 phase of the cell cycle was markedly inhibited by treatment with anti-IgM antibodies. Progression of B104 cells to the M phase of the cell cycle was found to be suppressed in the presence of anti-IgM antibodies. In contrast, both the entrance of G0/G1 phase cells into the S phase and the progression of S phase cells to the G2/M phase of the cell cycle did not seem to be inhibited significantly by treatment with anti-IgM antibodies. These results indicate that the mechanism of the inhibition of growth of B104 cells by anti-IgM antibodies is blockage of the transition from the G2 to the M phase of the cell cycle. In contrast to anti-IgM antibodies, anti-IgD antibodies could not cause growth inhibition of B104 cells at all. B cell growth factors such as IL-4 and IL-6 had no effect on the inhibition of growth of B104 cells by anti-IgM antibody. IFN-alpha and -beta, which have no B cell growth factor activity, did increase the number of cells that survived the treatment with anti-IgM antibodies. B104 is an excellent experimental model for the study of the mechanism of signal transduction through sIg as well as the functional difference between sIgM and sIgD.

Antibodies, Anti-Idiotypic↗
PubMed1989

[Epidemiological aspects of enteritis due to Campylobacter jejuni].

From September 1986 through July 1987, all fecal specimens obtained from infants and children who visited the pediatric clinic of the Shizuoka General Hospital with complaints of abdominal pain or diarrhea were examined for thermophilic Campylobacters. Bacteriological and epidemiological studies were performed on household contacts. The mothers of the patients were compared with the mothers of age-matched control subjects. Bacteriological examination of animals in 49 primary schools in Shizuoka city was performed. C. jejuni was isolated from 47 (9.4%) of the 499 feces samples, occupying first place in the bacterial etiology of acute bacterial enteritis. Infants and young children below 10 years of age comprised 81% of the total cases. Fourteen (13%) strains of C. jejuni were isolated in 9 families among 105 household contacts of the index patients. Six symptomatic contacts in two households had eaten the same suspected chicken as the respective index patients. In three families, C. jejuni was isolated from the remainder of the chicken. The serotype of these isolates was identical to that of the isolates from the index cases and the other family members. It was also noted that the same chopping boards were used for the preparation of salads after cleansing with water. In two index cases, the antibody of convalescent serum against C. jejuni isolated from the chicken, as estimated by passive hemagglutination method, ranged from 1:320 to 1:1280. These facts strongly supported the assumption that they had been infected by the chicken. The remaining persons were asymptomatic and the possibility was left that the index cases had been secondarily infected by these carrier persons.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

[Clinical evaluation of cefodizime in children].

Cefodizime (THR-221, CDZM), a new parenteral cephalosporin, was evaluated for its efficacy and safety in 20 children with bacterial infections (Table 1), and the following results were obtained. 1. CDZM was administered in 3 or 4 divided doses at daily dosages ranging from 54.5 to 84.2 mg/kg administered by 30 minutes drip infusion or intravenous injection to 20 patients (7 cases of acute tonsillitis, 6 cases of pneumonia, 2 cases each of bronchitis and suppurative cervical lymphadenitis, and 1 case each of acute pharyngitis, acute enteritis and furunculosis) and the following clinical results were obtained: excellent, 7 cases; good, 11 cases; fair, 2 cases. The overall efficacy rate was 90% (Table 4). 2. MICs of CDZM against 15 strains of isolated organisms are shown in Table 2. MICs against all 7 strains of Haemophilus influenzae were less than 0.025 micrograms/ml. MIC against 1 out of 5 strains of Streptococcus pneumoniae was 0.05 micrograms/ml and those against 2 strains were 0.10 micrograms/ml and against the other 2 were 0.20 micrograms/ml. MICs against 3 strains of Staphylococcus aureus were 1.56, 25 and higher than 100 micrograms/ml, respectively. 3. No clinical adverse reaction was observed in any of the 20 patients. Eosinophilia was observed in 2 cases. A slight elevation of S-GOT was found in 1 patient (case No. 8) and moderate elevation of S-GOT and S-GPT in another (case No. 18) (Table 4). In case No. 18, the S-GOT and S-GPT activity improved after the administration of the drug was stopped.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMedDate not supplied

Effect of beta-aminopropionitrile and hyaluronic acid on repair of collagenase-induced injury of the rabbit Achilles tendon.

Collagenase was injected into the Achilles tendon of both hind legs of 10 clinically normal adult male New Zealand white rabbits. One month after induction of the injury, beta-aminoproprionitrile (BAPN) or hyaluronic acid (HA) was injected into the tendon core of the right hind leg of each rabbit, the left hind leg being left untreated. The treatment effects were evaluated by electron microscopy and analysis of the glycosaminoglycan (GAG) content of samples at 2 and 6 months post-treatment. At 2 months, collagen fibrils in tendons from both hind legs were relatively small in diameter, irregularly arranged, and interspersed with abundant active tenocytes as compared with those in normal tendon uninjured by collagenase. In the matrix, the amount of HA increased, but chondroitin-6-sulphate was eliminated. At 6 months, BAPN-treated tendons had small-diameter, regularly arranged collagen fibrils. HA-treated tendons, on the other hand, had large diameters, as well as regularly arranged collagen fibrils by comparison with non-treated tendon. The results suggest that HA, unlike BAPN, promoted healing.

Achilles Tendon↗