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H Mohri

Publications and source records attributed to H Mohri.

At least 55 records · Page 3Linked to original sources
PubMed1998

Two different IL-13 receptor chains are expressed in normal human skin fibroblasts, and IL-4 and IL-13 mediate signal transduction through a common pathway.

IL-13 and IL-4, pleiotropic immune regulatory cytokines, have been shown to mediate similar prominent effects in human fibroblast cell lines. However, molecular mechanisms for their redundant effects are not known. Here, we have investigated the structure of IL-13 receptors (IL-13R) and molecular mechanisms of signal transduction through IL-13 and IL-4 receptors in non-transformed normal skin fibroblast cell lines. We demonstrate that high-affinity IL-13R is expressed in normal skin fibroblast cell lines. Upon [125I]1L-13 cross-linking, a approximately 60-70 kDa band was observed in sk559 and sk574 fibroblast cell lines. By RT-PCR analysis, mRNA for IL-13R alpha, IL-13R alpha' and IL-4Rbeta chains were expressed; however, the IL-2Rgamma chain, shown to participate and modulate IL-4 and IL-13 binding, was not expressed in any of the cell lines examined. The Janus kinase (JAK)2 and Tyk2 were phosphorylated in response to IL-4 or IL-13 in sk559 and sk574 cell lines. JAK1 was also phosphorylated in one of two cell lines while JAK3 was present but not phosphorylated in any of the cell lines studied. A signal transduction and activator of transcription (STAT)6 was also activated in response to both IL. An insulin receptor substrate (IRS)-1 was constitutively phosphorylated and its phosphorylation level was augmented in response to both IL. These results suggest that the mechanism of signal transduction through IL-13 and IL-4 receptors in human fibroblast cell lines is similar, and this may, at least in part, be responsible for the redundant effects of these two cytokines. In addition, JAK2 tyrosine kinase instead of JAK3 appears to play a major role in IL-4- and IL-13-induced signal transduction in human fibroblasts.

Affinity Labels↗
PubMed1998

Autoantibody inhibits binding of von Willebrand factor to glycoprotein Ib and collagen in multiple myeloma: recognition sites present on the A1 loop and A3 domains of von Willebrand factor.

A 49-year-old man with multiple myeloma (IgG-lambda Bence-Jones protein positive) presented a bleeding tendency: characterized intramuscular hemorrhage. Coagulation studies showed a von Willebrand factor (vWF) defect (Duke bleeding time > 20 min; ristocetin cofactor activity [vWF:RC] < 6%; significant reduction of large multimers of vWF. Mixing study suggested the presence of inhibitor directed against vWF:RC activity and collagen binding activity of vWF. The inhibitor was identified as an antibody of the IgG class. The inhibitor blocked the interaction of vWF with glycoprotein Ib in the presence of ristocetin, as did the pepsin-digested fragment of the inhibitor [F(ab)2'], but neither blocked botrocetin-mediated interaction of vWF with glycoprotein Ib. They also inhibited the binding of vWF to immobilized collagen type I. The inhibitor and the F(ab)2' reacted strongly with native vWF and fragment I (amino acids 911-1365) and with the 39/34 kDa fragment (amino acids 480/481-718), but not with fragment II (amino acids 1366-2050) and fragment III-T2 (heavy chains, amino acids 273-511; light chains, amino acids 674-728). We conclude that the IgG antibody inhibits both vWF:RC activity and the binding of vWF to collagen by reacting with the epitopes present on the A1 loop and A3 domains of vWF.

Autoantibodies↗
PubMed1998

Comparison of intranasal and intramuscular immunization against human immunodeficiency virus type 1 with a DNA-monophosphoryl lipid A adjuvant vaccine.

We compared immune responses to intranasal and intramuscular DNA vaccinations against human immunodeficiency virus type 1 with monophosphoryl lipid A (MPL) used as an adjuvant. Both routes of vaccination resulted in similar levels of cell-mediated immunity, but the intestinal secretory immunoglobulin A response was higher following intranasal immunization than after intramuscular immunization. MPL demonstrated its adjuvanticity in vaccination by both routes.

AIDS Vaccines↗
PubMed1998

Induction of systemic and mucosal immune responses to human immunodeficiency virus type 1 by a DNA vaccine formulated with QS-21 saponin adjuvant via intramuscular and intranasal routes.

Induction of mucosal and cell-mediated immunity is critical for development of an effective vaccine against human immunodeficiency virus (HIV). We compared intramuscular and intranasal immunizations with a DNA vaccine encoding env of HIV-1 and evaluated the QS-21 saponin adjuvant for augmentation of the systemic and mucosal immune responses to HIV-1 in a murine model. Vaccination via the two routes elicited comparable systemic immune responses, and QS-21 consistently enhanced antigen-specific serum immunoglobulin G2a (IgG2a) production, delayed-type hypersensitivity reaction, and cytolytic activity of splenocytes. Intestinal secretory IgA production and cytolytic activity of the mesenteric lymph node cells are preferentially elicited by intranasal immunization, and QS-21 augmented these activities as well. This adjuvant augmented production of interleukin-2 (IL-2) and gamma interferon (IFN-gamma) associated with decrease in IL-4 synthesis by antigen-restimulated splenocytes. The serum immunoglobulin subtype profile showed a dominant IgG2a response and less strong IgG1 and IgE production in a QS-21 dose-dependent manner. As expected, enhancements of humoral and cell-mediated immune responses by QS-21 were abrogated by treatment with anti-IL-2 and anti-IFN-gamma monoclonal antibodies. These results suggest that the intranasal route of DNA immunization is more efficient than the intramuscular route in inducing mucosal immunity mediated by sIgA and mesenteric lymphocytes. Furthermore, QS-21 is able to act as a mucosal adjuvant in DNA vaccination and demonstrates its immunomodulatory property via stimulation of the Th1 subset. This study emphasizes the importance of the route of immunization and the use of an adjuvant for effective DNA vaccination against HIV-1.

Adjuvants, Immunologic↗
PubMed1998

Residual leukemic cell counts in the bone marrow at the end point of intensive induction therapy may be a prognostic factor for acute myeloblastic leukemia in adults.

Between January 1990 and May 1994, 59 previously untreated adult patients with acute myeloblastic leukemia (AML) were treated with a combination of behenoyl-cytosine-arabinoside (BHAC), daunorubicin (DNR), 6-mercaptopurine (6-MP) and prednisolone (PSL). Forty one patients (69.5%) achieved complete remission (CR). The Kaplan-Meier analysis revealed an actuarial probability for remaining in remission of 36% in patients who achieved remission and a survival of 29% in all patients at 5 years. A favorable factor relative to achieving CR was performance status (P=0.04). In addition the presence of 300 cells/microl or less of residual leukemic cell counts in the bone marrow at the end point of induction therapy tended to favor remission (P=0.06) using the multivariate analysis with a multiple logistic regression model. In addition the residual leukemic cells counts of less than 300/microl in the bone marrow at the end point of induction therapy was the most significant factor for durable remission (P=0.05) by the Cox's proportional hazard model. We concluded that residual leukemic cells counts in the bone marrow at the end point of intensive induction therapy is a valuable prognostic factor for adults receiving response-oriented individualized induction therapy for AML.

Adolescent↗
PubMed1998

[Chronic myelogenous leukemia with long-term hypoplasia induced by alpha-interferon and hydroxyurea].

A 48-year-old woman was admitted with chronic myelogenous leukemia in November, 1996 and was treated with hydroxyurea (HU), because of marked leukocytosis; WBC 404,000/microliter. On January 29, 1997, administration of HU was stopped, and treatment of alpha-interferon (IFN alpha) was started with 6x 10(6)U, every day. However, the WBC count rose from 19,600/microliter to 56,800/microliter, and the combination of IFN and 2,000 mg of HU was started on February 4. The dose of HU was reduced to 500 mg on February 27, and the IFN administration was reduced to 3 times a week from April 4, because the WBC count was less than 10,000/microliter. Pancytopenia was revealed in May. The bone marrow biopsy specimen demonstrated marked hypoplastic changes, and chromosome analysis of bone marrow cells showed Philadelphia chromosome in all 20 metaphases. Treatment was interrupted for 7 months, but hematologic parameters did not recover. There were 9 cases reported in detail with bone marrow hypoplasia induced by IFN. One patient received IFN alone and 8 patients received anti-cancer drugs before treatment of IFN. We concluded that great care must be taken for IFN treatment of CML.

Antineoplastic Agents↗
PubMed1998

Intranasal administration of demopressin (DDAVP) for type 1 and type 2A von Willebrand disease.

Desmopressin was administered intranasally to seven patients with von Willebrand disease (type 1: 4 patients, type 2A: 3 patients) to assess the response and safety. von Willebrand factor antigen ranged from 8% to 60% before treatment and increased significantly after intranasal DDAVP administration (the median relative increase: two- to threefold). Factor VIII levels also increased substantially over baseline levels after intranasal administration. Before treatment ristocetin cofactor activity was 32 +/- 12% in patients with type 1 vWD and 9 +/- 5% in patients with type 2A vWD. After intranasal administration, the levels of ristocetin cofactor activity increased to 56 +/- 21% and 29 +/- 9%, respectively. The bleeding time was normalized in 86% of the patients. The abnormality of vWF multimers in type 1 vWD returned more or less to normal after intranasal DDAVP administration whereas that in type 2A vWD did not. The intranasal administration of DDAVP is safe and effective for minor bleeding episodes and is adaptable for home use in patients with type 1 and type 2A vWD.

Administration, Intranasal↗
PubMed1998

[Prospective matched control study concerning the treatment and quality of life of hemophiliacs with inhibitors].

Factor VIII (IX) inhibitors represent one of the most serious problems for the treatment of patients with hemophilia. The Blood Products Research Organization (Japan) has supported a study group for treatment of hemophiliacs with inhibitors. In 1995 the study group started a prospective matched control study of hemophiliacs with and without inhibitors and compared such factors as quality of life and economic cost. Each inhibitor patient was matched with a control patient in terms of age, type of hemophilia, and severity of hemophilia. A total of 136 patient-pairs were enrolled. Bleeding episodes were more frequent in the control group than in the inhibitor group. Days of hospitalization, days in wheelchairs, and the number of impaired joints were significantly higher for the inhibitor group. Number of blood-product infusions, days of bed rest at home, and days of brace use were the same for both groups. Blood-product expenditures were significantly higher for the inhibitor group than for the control group (yen 10,872,283/patient/year vs. yen 4,327,542/patient/year). Our study highlighted the higher cost of treatment and lower quality of life for hemophiliaes with Factor VII inhibitors.

Adult↗
PubMed1997

A synthetic peptide, FN-C/H-V, from the C-terminal heparin-binding domain of fibronectin promotes adhesion of PMA stimulated U937 cells.

Hematopoietic cells differentially bind to the C-terminal heparin-binding domain of fibronectin depending on the activation state of integrin alpha 4 beta 1. In this study, we have identified a synthetic peptide derived from the C-terminal heparin-binding domain of fibronectin that promotes adhesion of PMA-treated U937 cells (a monocytic cell line) in a dose-dependent manner. A peptide (FN-C/H-V; residues Gln1892 to Gly1910) was active to inhibit adhesion of PMA-treated U937 cells to the 29-kDa fragment comprising the C-terminal heparin-binding domain of fibronectin. A peptide with scrambled version of FN-C/H-V lost the inhibitory activity on the adhesion. Furthermore, the IgG-conjugated FN-C/H-V promoted the adhesion of PMA-treated U937 cells to an extent comparable to that of the 29-kDa fragment. The adhesion of PMA-treated U937 cells on IgG-conjugated FN-C/H-V was inhibited both by anti-alpha 4 beta 1 antibody and by glycosaminoglycans including chondroitin sulfate and heparan sulfate. The other peptide, FN-C/H-II, was also a weak adhesion-promoting domain. These results suggest that the amino acid sequence defined by peptide FN-C/H-V contributes to the main adhesion-promoting activity of the 29-kDa fragment of fibronectin to stimulated U937 cells. The regulation of interactions of alpha 4 beta 1 integrin and glycosaminoglycans with ligands in fibronectin may have important implications for the migration and function of U937 cells.

Amino Acid Sequence↗
PubMed1997

The evidence of clonal evolution with monosomy 7 in aplastic anemia following granulocyte colony-stimulating factor using the polymerase chain reaction.

We present here the case of a Japanese female patient with aplastic anemia who developed monosomy 7 and clonal evolution following a treatment with recombinant human granulocyte colony-stimulating factor (rhG-CSF). At the onset of aplastic anemia, cytogenetic analysis was 46, XX and X-inactivation/methylation analysis revealed a polyclonal pattern. After 4 months of administration of rhG-CSF, she had 45, XX, -7 and a clonal pattern, although there were no morphological evidence of a myelodysplastic syndrome or leukemia. The ratio of monosomy 7 to normal analyzed by fluorescence in situ hybridization decreased after discontinuation of rhG-CSF and there were still no dysplastic changes and/or increased numbers of blasts. These results indicate that the acquisition of monosomy 7 following rhG-CSF treatment dose not always cause clonal evolution to induce hematological malignancies.

Anemia, Aplastic↗
PubMed1997

Esophageal metastasis from prostate cancer: diagnostic use of reverse transcriptase-polymerase chain reaction for prostate-specific antigen.

An extremely rare case of esophageal metastasis from prostate cancer is reported. A 65-year-old man presented with anorexia and back pain. Upper gastrointestinal X-ray fluoroscopy and endoscopy revealed a shallow longitudinal ulcer, with converging mucosal folds, approximately 5 cm above the esophagogastric junction. The histological diagnosis of the biopsied specimen was adenocarcinoma. Blood biochemistry revealed elevated serum prostate-specific antigen (PSA) and gamma-seminoprotein levels. Ultrasonography of the prostate disclosed a hypoechoic lesion in the left lobe, and needle biopsy led to the diagnosis of prostatic adenocarcinoma. Since there was no finding suggestive of a primary lesion, apart from that in the prostate, we conducted reverse transcriptase-polymerase chain reaction (RT-PCR) for PSA. PSA-positive mRNA was demonstrated in the tissue of the esophageal tumor. There are three reports on metastasis to the esophagus from prostate cancer, but this is the first case of esophageal metastasis from prostate cancer without any evidence of metastasis to other organs. The importance of RT-PCR for the diagnosis of primary lesions of metastatic cancer is discussed.

Adenocarcinoma↗
PubMed1997

Eradication of minimal residual disease during graft-versus-host reaction induced by abrupt discontinuation of immunosuppression following bone marrow transplantation in a patient with Ph1-ALL.

We observed a patient in whom graft-versus-host disease (GVHD) appeared to induce a positive effect. This 32-year-old male with Philadelphia chromosome-positive acute lymphoblastic leukemia received a bone marrow transplant (BMT) from an HLA-identical sibling donor. We analyzed the bone marrow with the reverse transcriptase-polymerase chain reaction to screen for the minor bcr/abl transcript, which indicates the presence of minimal residual disease (MRD). MRD was present in the pre- and post-transplant phases. There was no evidence of acute GVHD by post-transplant day 45. We abruptly discontinued the immunosuppressive therapy in an attempt to eliminate MRD by inducing an antileukemic reaction during GVHD. GVHD associated with diarrhea and liver dysfunction developed on day 64. On day 105, MRD disappeared and GVHD was treated with prednisolone and cyclosporin. The disappearance of MRD may have been due to the graft-versus-leukemia (GVL) effect mediated by the alloimmune response of donor T lymphocytes. These findings suggest that induction of the GVL effect may be useful for eliminating MRD after BMT in leukemia patients at high risk of recurrence of the disease.

Adult↗
PubMed1997

Subcutaneous transposition of the ovary following hysterectomy.

OBJECTIVES: Preservation of ovarian function at hysterectomy in pre-menopausal women is desirable. A possibly malignant tumor from retained ovary is a concern. We demonstrate a new technique for exteriorization of the ovaries. METHOD: In 27 patients, the infundibulopelvic ligament was mobilized. The retroperitoneal space was then widely opened. The ovary was gently pulled through a fascial incision and fixed on the fascia followed by skin closure. RESULTS: Cystic formation was common (66.7%). Four patients had extreme enlargement of the transposed ovary. A needle puncture revealed intra-ovarian hematomas or fluid retention. One had puncture of the translocated ovary for in vitro fertilization more than two years following transposition. CONCLUSIONS: Possible advantages are (1) early detection and diagnosis of ovarian cysts, (2) easy surgical access to remove ovarian cysts, (3) transposition of ovaries outside the radiation field and (4) in vitro fertilization is facilitated. Comparative study for ovarian function is ongoing.

Abdomen↗
PubMed1997

Synthetic peptide from the V3 loop consensus motif with a potent anti-HIV activity inhibits ristocetin-mediated vWF-GPIb interaction.

The V3 loop consensus motif. Arg-Gly-Pro-Gly-Arg-Ala-Phe-Val-Thr-Ile (HIV-1 IIIB), inhibits an interaction of HIV with CD4-positive lymphocytes. Recently, both proline-rich peptides and peptides containing proline-glycine loops (beta-turns) form a complex with ristocetin dimers. These peptides interact with ristocetin-loaded platelet membrane glycoprotein (GP) Ib and act as inhibitors of von Willebrand factor (vWF)-GPIb interaction by preventing the subsequent formation of ristocetin dimer bridges. The Pro-Gly sequence is also present in the V3 loop consensus motif, Arg-Gly-Pro-Gly-Arg-Ala-Phe-Val-Thr-Ile (HIV-1 IIIB). In this report, we have evaluated the effect of the HIV-1 IIIB peptide on vWF binding to GPIb. This peptide only inhibited vWF binding to GPIb as well as platelet aggregation in the presence of ristocetin while it had no effect on botrocetin-mediated vWF interaction with platelets. The peptide inhibited a binding of anti-vWF monoclonal antibody (RG-46) to immobilized vWF. Furthermore, ristocetin inhibited the binding of HIV-1 IIIB peptide to immobilized CXC-chemokine receptor-4 (CXCR-4) peptide. These results indicate that ristocetin may prevent HIV infection and would be useful a tool to understand the mechanism of HIV tissue tropism and infection.

Amino Acid Sequence↗
PubMed1997

Variant of intron 22 inversions in the factor VIII gene in severe hemophilia A.

Recurrent DNA inversions, which disrupt the factor VIII (FVIII) gene, generally occur between a region of intron 22 (int22h) and one of two homologous copies of this region, located 300 to 400 kb telomeric to the FVIII gene. This report describes a patient with severe hemophilia A and a high level inhibitor with atypical hybridization patterns. A Bcl I Southern blot assay was altered to 17.5, 16, and 14 kb. His mother and two out of four aunts tested had normal and abnormal restriction patterns which led to a total of five different fragments, suggesting that they were carriers. The Xba I plus Kpn I restriction fragment-length polymorphism in intron 22 by Southern blotting using the same probe (probe a) yielded the 6.2 kb polymorphic band, with a clearly separated 6.6 kb band from the non-factor VIII region; an alternative int22h hybridization probe (probe x) detected no additional fragment. These results suggest that probe a as well as probe x could recognize an intron-22-sized fragment. This report shows a variation in the number of int22h copies although we could not find the inversion junction.

Adult↗