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Biomedical subjects

H Mizoguchi

Publications and source records attributed to H Mizoguchi.

At least 343 records · Page 19Linked to original sources
PubMed1989

Lateral nasal gland secretion in the anesthetized ferret.

In anesthetized ferrets, we cannulated the duct of the lateral nasal gland for direct collection of glandular liquid. Administration of methacholine and substance P into the internal carotid artery via a retrograde cannulation of the lingual artery produced a dose-dependent increase in glandular output. The dose-response curve to methacholine was significantly shifted to the right by atropine. The secretory response to substance P was only partially inhibited by atropine at the dose that completely blocked secretion produced by methacholine (51 nmol/kg), suggesting the involvement of noncholinergic as well as cholinergic pathways. Phosphoramidon, an inhibitor of neutral endopeptidase, significantly potentiated the action of substance P. The analyses of electrolyte contents in glandular secretion revealed the presence of Na+, K+, and Cl-. The sum of the electrolyte concentrations indicated that the secretion was close to isotonic. The anesthetized ferret is a useful in vivo model for the study of physiology and pathophysiology of nasal secretion.

Animals↗
PubMed1989

Effects of neurokinins on ion transport and sulfated macromolecule release in the isolated ferret trachea.

The secretory actions of substance P (SP) were studied by examining its effects on ion transport and sulfated macromolecule release in the isolated ferret trachea. Responses to serosally administered SP were unmasked by thiorphan, suggesting that SP administered by this route was degraded by neutral endopeptidase. Therefore, the serosal actions of neurokinins and neurokinin analogues were studied in tissues pretreated with thiorphan. In thiorphan-treated tissues, SP dose-dependently increased the short-circuit current (Isc) with a maximum increase of 0.50 +/- 0.07 mueq/cm2.h above baseline. The SP-induced increase in Isc was inhibited by bumetanide but not by amiloride, suggesting the involvement of electrogenic Cl- secretion. The direct measurement of ion fluxes, however, failed to detect a significant unilateral movement of Cl- from the serosa to mucosa, probably due to a relatively small and transient increase in Isc produced by SP. Instead, SP (10(-6) M) induced large, electroneutral secretion of Na+ and Cl-. In addition, SP stimulated sulfated macromolecule output. The rank order of potency in increasing both Isc and sulfated macromolecule release among neurokinins and their analogues was SP = SP-methyl ester greater than neurokinin A greater than neurokinin B greater than senktide. These findings indicate that the secretory responses to SP are probably mediated by NK-1 receptors.

Amiloride↗
PubMed1989

Effect of recombinant hemopoietic growth factors on human megakaryocyte colony formation in serum-free cultures.

The effects of recombinant hemopoietic factors on the clonal growth of human megakaryocyte progenitors were explored using serum-free cultures of nonadherent and T-cell-depleted marrow cells. Recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) supported megakaryocyte colony formation in a dose-dependent manner, the activity being lower than that of recombinant interleukin 3 (rIL-3). Recombinant IL-3 and rGM-CSF acted synergistically on megakaryocyte colony formation when rGM-CSF was added to cultures containing suboptimal concentrations of rIL-3. However, the number and size of colonies did not increase with rGM-CSF when cultures were plated with an optimal dose of rIL-3. Recombinant erythropoietin (rEpo) by itself did not stimulate the growth of megakaryocyte progenitors. Recombinant Epo did, however, produce a significant increase in the number and size of megakaryocyte colonies in the presence of rIL-3 or rGM-CSF. Other factors, including recombinant granulocyte colony-stimulating factor, recombinant interleukin 1 alpha, recombinant interleukin 4, and recombinant interleukin 6 showed no capacity to generate or enhance megakaryocyte colony formation when added to cultures alone or in combination with varying concentrations of rIL-3. These results show that rIL-3, rGM-CSF, and rEpo affect human megakaryocytopoiesis by themselves or by interacting with each other.

Blood Physiological Phenomena↗
PubMed1989

Effect of recombinant GM-CSF and recombinant G-CSF on colony formation of blast progenitors in acute myeloblastic leukemia.

The colony-promoting activities of recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) and recombinant granulocyte colony-stimulating factor (rG-CSF) on primary and secondary colony formation by blast progenitors (leukemic colony-forming units [L-CFU]) from 21 patients with acute myeloblastic leukemia (AML) were examined using blast colony assay and compared to colony promotion stimulated by phytohemagglutinin-stimulated leukocyte-conditioned medium (PHA-LCM). Recombinant GM-CSF stimulated blast colonies in 13 out of 20 cases examined (1 case not done). The magnitude of stimulation by rGM-CSF varied significantly according to the type of AML, but in general was lower than that of PHA-LCM. Blast cells of type M1 did not form any colonies with rGM-CSF, although numerous colonies were produced with PHA-LCM. Type M4 blasts formed fairly large numbers of colonies, though slightly less than those stimulated by PHA-LCM. Blasts of type M2 and M5 formed colonies with the stimulation of rGM-CSF, but the numbers were considerably smaller than type M4 and those stimulated with PHA-LCM. Recombinant G-CSF stimulated blast colonies in only 5 out of 21 cases, 3 of them being type M2. The number of cases responding to rG-CSF was significantly smaller than that responding to rGM-CSF, and even in cases in which colonies were formed, the magnitude of stimulation was minimal. From these results it seems likely that blast cells of different types of AML require a different kind of CSF for their optimal growth; type M4 blasts responded to the stimulation of rGM-CSF well, but blasts of other types of AML responded poorly. Thus, except for type M4, CSF(s) other than rGM-CSF seems to be required for the sufficient growth of L-CFU. Recombinant G-CSF is not likely to play an essential role in the proliferation of leukemic blasts of most types. Previous exposure to rGM-CSF and rG-CSF did not alter the self-renewal capacity, cellular phenotype, and morphology of colony cells, indicating that the direction and degree of differentiation of L-CFU stimulated by rGM-CSF or rG-CSF were not different from those stimulated with PHA-LCM.

Colony-Stimulating Factors↗
PubMed1988

Infrequent loss of chromosomal heterozygosity in human stomach cancer.

By molecular genetic approach using polymorphic DNA markers which detect allelic deletion at specific chromosomal loci, we analyzed 30 human stomach cancers for possible loss of chromosomal heterozygosity. We analyzed 25 loci on 18 different chromosomes covering regions frequently deleted in several types of cancers. Loss of chromosomal heterozygosity was observed only in five of 30 cases examined, and it was infrequently detected at 10 loci on seven different chromosomes including chromosome 1 in two of 12 cases, chromosome 12 in one of four cases and chromosome 13 in three of 27 cases. It was also observed at loci on chromosomes 11, 14, 16, and 19 with very low frequency (less than 10%), but not on other chromosomes: chromosomes 3, 5, 6, 9, 10, 15, 17, 18, 20, and 22. Thus, in human stomach cancer, loss of heterozygosity occurs infrequently even at chromosomal loci often deleted in other types of cancers.

Alleles↗
PubMed1988

Cytotoxicity of interleukin-2-activated lymphocytes for autologous normal blood mononuclear cells.

When peripheral blood mononuclear cells (PBMC) were cultured for 5 days with 1000 U/ml of recombinant interleukin-2 (IL-2), lymphokine-activated killer (LAK) cytotoxicity for normal autologous and allogeneic PBMC developed. Autologous PBMC lytic activity was detected in media containing autologous serum and was dependent on the concentration of IL-2 added to the cultures. When purified T lymphocytes, B lymphocytes, monocytes and large granular lymphocytes were compared for their susceptibilities to lysis by autologous LAK, monocytes and B lymphocytes were found to be the most susceptible. In addition, mitogen-induced blasts were more susceptible than unstimulated lymphocytes. Since PBMC cultured in IL-2-containing medium consisted mainly of CD3-positive T lymphocytes and CD16-positive natural killer cells, and since treatment with anti-CD3 monoclonal antibody, but not anti-CD16 monoclonal antibody, reduced LAK activity for normal target cells, T cells appeared to be the effectors for LAK activity in the LAK normal target lysis system.

Cytotoxicity, Immunologic↗
PubMed1988

Effect of recombinant human erythropoietin on the anemia of chronic renal failure.

Phase I and Phase II studies of recombinant human erythropoietin (rhEpo) were conducted in normal volunteers and in anemic patients with chronic renal failure on maintenance hemodialysis. Three hundred U/person of rhEpo was administered intravenously to healthy normal volunteers in the Phase I study, resulting in no subjective or objective changes. In the Phase II study, 66 patients with chronic renal failure on maintenance hemodialysis with less than 20% hematocrit values were treated with rhEpo in doses of 50 U/kg to 200 U/kg two or three times a week. Hematocrit values increased significantly during the 12 weeks, and the patients' conditions improved. Patients previously requiring blood transfusions became transfusion-independent during our study. There were no obvious side effects, thus indicating the safety and efficacy of rhEpo in the anemia of chronic renal failure.

Adult↗
PubMed1988

Characterization of interleukin 2-expanded human peripheral blood lymphocytes: not only NKH-1+-NK cells but also NKH-1+ and NKH-1- T cells are LAK effectors.

In vitro culture of human peripheral blood mononuclear cells (PBMC) with interleukin 2 (IL-2) results in the expansion of lymphocytes including lymphokine-activated killer (LAK) cells. Using flow cytometry, studies were undertaken to determine the phenotype and LAK activity of each subset of lymphocytes expanded in vitro as a result of incubation for 2 weeks with 2500 U/ml of recombinant IL-2. Such expanded PBMC, when examined by two-color staining with various combinations of anti-CD3, 4, 8, 16, and NKH-1 monoclonal antibodies, consisted of the following six subgroups of cells: (1) CD3+4+8-, (2) CD3+4-8+, (3) CD3+4-8-, (4) CD3-16+NKH-1+, (5) CD3-16-NKH-1+, and (6) CD3-16-NKH-1-. Of the six subgroups, all five subgroups that could be tested, i.e., CD3+ T cells (CD3+4+8-, CD3+4-8+, CD3+4-8-), CD16+ natural killer (NK) cells (CD3-16+NKH-1+), and CD3-16-NKH-1- non-T non-NK cells, possessed LAK activity. Both NKH-1- as well as NKH-1+ T and non-T cells possessed LAK activity.

Antibodies, Monoclonal↗
PubMed1988

Upper respiratory tract involvement in adult T-cell leukemia.

Adult T-cell leukemia (ATL) is characterized by peripheral lymph node enlargement, hepatosplenomegaly and skin lesions. The association of local mass lesions of other organs with ATL is extremely rare. This report describes a 57-year-old woman with chronic type ATL with associated local tumor masses in the nasal cavity, paranasal sinuses and larynx as well as skin infiltration. Histologic investigation of the skin lesion and nasal mucosa revealed non-Hodgkin lymphoma, diffuse, mixed type. Her chief complaints were progressive dyspnea and hoarseness. Leukemic cell masses in her upper respiratory tract caused narrowing of the airway, which was responsible for her complaints.

Deltaretrovirus Infections↗
PubMed1988

Inhibition of human granulocyte-macrophage colony formation by interleukin 2-treated lymphocytes.

The effects of interleukin 2 (IL-2)-treated lymphocytes on human myeloid progenitors (CFU-GM) were studied. When peripheral blood mononuclear cells (PBMC) were cultured for 3 days with recombinant IL-2, they developed lymphokine-activated killer (LAK) activity against normal bone marrow cells, and also suppressed colony formation by CFU-GM. Suppression of CFU-GM was found to be mediated mainly by natural killer (NK) cells, and to a lesser degree by T cells according to the results showing that isolated NK cells and T cells exhibited strong and moderate suppressor function, respectively. Since the levels of LAK activity and of CFU-GM inhibitory activity were not parallel in each individual, inhibition of CFU-GM does not seem to be due to a direct lytic action by LAK cells. This possibility was supported by our finding that the supernatant of IL-2-treated PBMC contained factor(s) that inhibited CFU-GM colony formation.

Depression, Chemical↗
PubMed1988

Clonal growth of human megakaryocyte progenitors in serum-free cultures: effect of recombinant human interleukin 3.

Human megakaryocyte colony formation was observed in serum-free agar cultures with a medium containing deionized bovine serum albumin, iron-saturated transferrin, 2-mercaptoethanol, and recombinant human interleukin 3 (IL-3). Megakaryocyte colonies were identified in situ by the alkaline phosphatase anti-alkaline phosphatase technique, using monoclonal antibody against platelet glycoprotein IIb/IIIa. Colony numbers reached a peak at day 14, with a mean of 47 megakaryocyte colonies (range 23-104) per 2 x 10(5) bone marrow mononuclear cells. Recombinant human IL-3 stimulated the growth of megakaryocyte progenitors. Similar results were obtained using nonadherent, T-cell-depleted mononuclear cells. These findings suggest that IL-3 stimulates the growth of megakaryocyte progenitors directly without activation of accessory cells, or the requirement of factors present in the serum or plasma. This serum-free culture system may be useful for studying the effects of purified natural and recombinant biological regulators on human megakaryocyte progenitors.

Colony-Forming Units Assay↗
PubMed1988

Relationship between an activated N-ras oncogene and chromosomal abnormality during leukemic progression from myelodysplastic syndrome.

The relationship between chromosomal abnormality and oncogene activation was investigated during leukemic progression in two patients with myelodysplastic syndrome (MDS). Both patients had partial or complete deletion of chromosome 5 in metaphase cells obtained throughout the progression to leukemia. Analysis with specific oligonucleotide probes revealed that bone marrow cells containing an activated N-ras oncogene proliferated in a dominant manner during the process of leukemic conversion in both patients. These observations suggest that the chromosomal abnormality may precede activation of the N-ras gene in these patients, and that both the chromosomal abnormality and the activated N-ras oncogene contribute to the development of leukemia.

Acute Disease↗