Biomedical subjects

T Akabane

Publications and source records attributed to T Akabane.

At least 37 records · Page 2Linked to original sources

PubMed1990

Natural killer cell immunodeficiency in siblings: defective killing in the absence of natural killer cytotoxic factor activity in natural killer and lymphokine-activated killer cytotoxicities.

A immunodeficiency of natural killer cells as effectors for natural killer and lymphokine-activated killer cytotoxicities was first demonstrated in siblings. Two of three male siblings persistently lacked natural killer activity against K562 target cells as assayed by a 51Cr-release assay: percent lysis values were less than 1.0% as compared to the normal lymphocyte values of 43.5% +/- 6.2% (mean +/- SD). Their lymphocytes did not develop natural killer cell activity by changing effector to target ratios, prolonging the incubation time, or stimulating them with interferon-alpha or interleukin 2. Numbers of lymphocytes bearing Leu-7, CD16, or NKH-1 were normal but those of Leu-7-, CD16+ cells were decreased as estimated by flow cytometry. Single cell-in-agarose assays showed normal numbers of natural killer cells capable of binding to a target cell but incapable of killing it. They had depressed levels of lymphokine-activated killer activity, which was totally eliminated by the treatment with OKT3 and complement. This result indicates that the patients' natural killer cells are also defective in the capacity to work as effectors for lymphokine-activated killer activity. The patients' natural killer cells did not produce natural killer cytotoxic factor activity. Antibody-dependent cellular cytotoxicity and cytotoxic T lymphocyte cytotoxicity were normal. These results demonstrate a selective natural killer cell deficiency as effectors for natural killer and lymphokine-activated killer cytotoxicities with a familial tendency, in which there is defective killing with the absence of natural killer cytotoxic factor activity.

Child↗

PubMed1989

Stimulation of connective tissue-type mast cell proliferation by crosslinking of cell-bound IgE.

Crosslinking of cell-bound IgE on mouse connective tissue-type mast cells (CTMC) by multivalent antigen or anti-IgE antibody induced clonal growth of CTMC in methylcellulose culture containing IL-3. Continuous presence of antigen, IgE antibody, and IL-3 in culture was required for extensive proliferation of CTMC. Optimal concentrations of antigen and anti-IgE antibody for proliferation of sensitized CTMC approximately corresponded to those for maximal histamine release from the cells, and it was observed that most dividing cells stimulated by antigen had pericellular degranulation halos in culture. Experiments of both single cell culture and serum free culture provided evidence for a direct effect of antigen stimulation on proliferation of CTMC. Neither accessory cells nor some factors in FCS were required for the clonal growth of CTMC in our culture condition. Compound 48/80, a direct stimulator of CTMC, also triggered histamine release from CTMC but failed to support their proliferation. These results suggest that stimulation of CTMC via IgE receptors not only triggers the release of chemical mediators from the cells but induces clonal growth of CTMC in the presence of IL-3. Our data indicate the possibility that antigen stimulation may play another role in the proliferation of CTMC.

Animals↗

PubMed1989

Giant lymph node hyperplasia (Castleman's disease) with spontaneous production of high levels of B-cell differentiation factor activity.

A 13-year-old girl presented with general fatigue, back pain, anemia, hyperimmunoglobulinemia, and a mediastinal mass on chest radiograph. A mass was surgically removed, and its histologic examination determined the diagnosis of giant lymph node hyperplasia (Castleman's disease). With removal of the hyperplastic lymph node, the clinical symptoms soon disappeared and the abnormal laboratory findings were markedly improved within 1 month: serum IgG levels decreased from 4350 mg/dl to 1829 mg/dl. Immunostaining on the lymph node sections revealed polyclonal B-lymphocyte and T-lymphocyte populations. The patient's lymph node cells were cultured without any mitogenic stimulation, and the culture supernatants were assayed for their B-cell differentiation factor (BCDF) activity to induce IgG production by our Epstein-Barr virus-transformed cell line. The patient's lymph node cells produced high levels of BCDF activity: the supernatants could increase the IgG production from 140 ng/ml to 410 ng/ml when the values became from 140 ng/ml to 142 ng/ml or 148 ng/ml with those of the control lymph node cells. These results suggest that the hyperimmunoglobulinemia and its prompt improvement with removal of the hyperplastic lymph node may have been related to the spontaneous production of high levels of BCDF activity by the lymph node cells in the patient.

Adolescent↗

PubMed1989

Dopamine inhibition of superoxide anion production by polymorphonuclear leukocytes.

To examine the modulatory effects of catecholamines on the respiratory burst in polymorphonuclear leukocytes (PMNs), dopamine was tested for its capacity to modify the superoxide anion (O2-) production by PMNs under their stimulation with several stimuli. Dopamine inhibited the O2- production by PMNs when PMNs were stimulated with N-formylated chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP), phorbol myristate acetate, or opsonized zymosan, whereas dopamine did not alter the PMN mobility. The values of percentage inhibition of the O2- production by FMLP-stimulated PMNs were 57% under treatment with 10(-5) mol/L and 83% with 10(-4) mol/L of dopamine. Isoproterenol also inhibited PMN O2- production in response to FMLP. Although a beta-adrenergic blockade, propranolol, diminished the isoproterenol-induced inhibition of the O2- production, it did not affect the inhibitory effect of dopamine. The increase in intracellular cyclic AMP levels in dopamine-treated PMNs was much smaller than the increase in isoproterenol-treated cells. Furthermore, dopamine inhibited the reduced nicotinamide-adenine dinucleotide phosphate-dependent O2- production by subcellular particles. These results indicate that dopamine inhibits PMN O2- production through its effect on PMN reduced nicotinamide-adenine dinucleotide phosphate-oxidase system rather than through its beta-adrenergic action.

Chemotaxis, Leukocyte↗

PubMed1989

Morphometric changes in glomerular anionic sites during aminonucleoside nephrosis.

Changes in glomerular anionic sites were examined morphometrically in nephrotic rats receiving daily subcutaneous injections of puromycin aminonucleoside (PAN). The high-iron diamine-thiocarbohydrazide-silver proteinate method showed that anionic sites composed of heparan sulfate proteoglycans formed a continuous band within the lamina rara externa of the glomerular basement membrane (GBM) in control rats. Only one day after the first injection of PAN, anionic site loss was already detectable, preceding the morphological changes in the epithelial cells. The number and size of the anionic sites decreased greatly between days 7 and 10, when urinary protein excretion began to appear. The number of anionic sites in the paramesangial regions (epithelial side of the mesangium) was slightly more reduced than that in the capillary walls. These results suggested that PAN directly injured the glomerular anionic sites and increased the permeability of the glomerulus to macromolecules. However, there was no complete correlation between the number of lost anionic sites and the level of urinary protein excretion. Thus protein excretion into the urinary space may be related not only to the loss of subepithelial anionic sites but also to dysfunction of the protein absorption mechanism in epithelial cells due to excessive permeation of macromolecules through the GBM.

Animals↗

PubMed1989

Acute lymphoblastic leukemia in a patient with pituitary dwarfism under treatment with growth hormone.

An 18-year-old male with pituitary dwarfism, who had been on replacement of growth hormone (GH) and thyroxine for 3.5 years, developed acute lymphoblastic leukemia (ALL). The GH replacement was discontinued, and he was treated with a conventional protocol for ALL. A complete remission was obtained after 10 weeks. Maintenance chemotherapy was given with reduced doses (1/4 to 1/2) of cytotoxic drugs. The platelet count soon reached 200,000/microL, but the hemoglobin level and white blood cell count improved only slowly, reaching 10.0 g/dL and 1,500/microL, respectively, after five months. He has been in complete remission with a hypocellular bone marrow for nearly 15 months. Since GH can stimulate the proliferation of some normal and leukemic hemato-lymphoid cells, the slow remission induction and the prolonged anemia and leukocytopenia after remission, may have been related to the absence of GH in this patient.

Adolescent↗

PubMed1989

Temperature-dependent formation of vacuolar and canalicular systems in association with degranulation in stimulated neutrophils.

Effects of temperature on the morphological changes and degranulation were studied in stimulated neutrophils. Neutrophils were stimulated by formyl-methionyl-leucyl-phenylalanine (FMLP) and cytochalasin B at 4 degrees C, 20 degrees C and 37 degrees C, and they were processed for electron microscopy and biochemical assays of myeloperoxidase (MPO) activity. When neutrophils were stimulated at 4 degrees C, they did not show apparent morphological changes nor release MPO activity. In the cells stimulated at 20 degrees C, there were many cytoplasmic vacuoles, localization of MPO-positive granules adjacent to the cell membrane and around the vacuoles, MPO-positive materials in the cavity of the vacuoles, and slightly decreased numbers of granules. They released moderate amounts of MPO activity. The neutrophils at 37 degrees C showed formation of small vacuoles and canaliculi and a marked decrease in the number of MPO-positive granules indicative of degranulation, and they released increased amounts of MPO activity. There were MPO-positive materials on the membrane and in the cavity of the vacuoles. Ruthenium red staining showed that the vacuoles were formed open outside the cell. These results indicate that the vacuolar systems are involved in degranulation in stimulated neutrophils and that their formation is dependent on temperature.

Cells, Cultured↗

PubMed1989

[Hereditary spherocytosis first diagnosed upon the development of aplastic crisis; a case report].

We report a Childhood case of hereditary spherocytosis (HS) first diagnosed upon the development of aplastic crisis. A 6-year-old boy presented with fever and anemia. Although there was neither icterus nor splenomegaly at first, mild icterus and splenomegaly gradually developed with improvement of anemia. The diagnosis of HS was made on the basis of the presence of numerous spherocytes on the peripheral smear, increased osmotic fragility and the auto-hemolysis test result. The severe anemia in the early course with a marked decrease in the bone marrow erythroid cells and the absence of icterus and splenomegaly indicate that it was due to aplastic crisis. In the virological study, anti-human parvovirus (HPV) antibody titers were increased: the values of anti-HPV IgM were high and those of anti-HPV IgG were suddenly elevated. We thus considered that this HS case developed aplastic crisis by HPV infection.

Anemia, Aplastic↗

PubMed1989

[Effect of a protein-bound polysaccharide, PSK, on human hemopoietic progenitors].

Using in vitro clonal culture assays, we investigated the effects of PSK, a protein-bound polysaccharide derived from the cultured mycelium of CM101, Coriolus versicolor (Fr.) Quél in Basidiomycetes, on human hemopoietic progenitors. PSK alone did not stimulate colony formation by human bone marrow progenitors. Although 1-100 micrograms/ml of PSK had no effects on colony formation stimulated by erythropoietin and medium conditioned by phytohemagglutinin-stimulated leukocytes, more than 1 mg/ml of PSK inhibited all types of colony formation. In contrast, medium conditioned by PSK-stimulated leukocytes significantly stimulated formation of various types of colonies including erythroid bursts, granulocyte and/or macrophage colonies, eosinophil colonies, megakaryocyte colonies and mixed hemopoietic colonies. It is speculated that administration of the optimal dose of PSK can reduce the hematological suppression of antitumor drugs.

Cell Division↗

PubMed1989

Long-term prognosis and residual abnormalities of idiopathic acquired aplastic anemia in children.

We evaluated the long-term prognosis and quality of cure of idiopathic acquired aplastic anemia in children. Of the 244 patients registered from 1965 to 1985, those registered in 1965-1975 and 1976-1985 had a survival rate of 50.1% and 62.0%. The percentage of cure, undertreatment and death was 30, 30 and 40%, respectively. About 40% of the patients with moderate cases, died dead or required frequent blood transfusions. In the case of pediatric patients, as the success rate of bone marrow transplantation was high. This modality should be considered for patients with moderate severity who require blood transfusion 3 months after the diagnosis and an HLA identical donor is available. Physical development was almost normal but 35% of the patients showed residual abnormalities such as bleeding tendency, and hepatic disorders due to treatment. Thrombocytopenia and ineffective hematopoiesis were observed in one-third of the patients and all of the patients showed abnormal committed stem cell assay. The CD 4/8 ratio was reduced in 50% of the patients and 15% exhibited psychological problems. These residual abnormalities last for years, and sometimes a lifetime.

Anemia, Aplastic↗

PubMed1988

Synergism of BSF-2/interleukin 6 and interleukin 3 on development of multipotential hemopoietic progenitors in serum-free culture.

We investigated the effects of B cell stimulatory factor 2/interleukin 6 (BSF-2/IL-6) on the development of murine hemopoietic progenitors using serum-containing culture and serum-free culture. In serum-containing culture, BSF-2 mainly supported multipotential blast cell colonies from spleen cells of normal and 5-fluorouracil (5-FU)-treated mice. In serum-free culture, no colony growth was seen in the presence of BSF-2. Addition of BSF-2 to the serum-free culture containing IL-3 resulted in a significant increase in the number of colonies formed from multipotential progenitors in spleen cells and bone marrow cells of 5-FU-treated mice, whereas no effects were seen on the number of single or oligolineage colonies formed by the spleen cells of normal mice. These results suggested that BSF-2 and IL-3 act synergistically on the multipotential progenitors but not on the maturer progenitors. When BSF-2 was added to a culture containing low concentrations of IL-3 (1 U/ml, 4 U/ml), which had little effect on colony formation, the number of total colonies formed by the spleen cells and bone marrow cells of 5-FU-treated mice increased significantly. The combination of BSF-2 and 40 U/ml of IL-3 resulted in a significant enlargement of GMM colonies. Thus, BSF-2 appears to enhance the sensitivity of multipotential hemopoietic progenitors to IL-3.

Animals↗

PubMed1988

Increased production of superoxide anion by neonatal polymorphonuclear leukocytes stimulated with a chemotactic peptide.

In order to assess the functional property of neonatal polymorphonuclear leukocytes (PMNs), we studied their chemoattractant-stimulated superoxide anion (O2-) production using a soluble chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) as a PMN stimulus. O2- production by neonatal PMNs was increased: when stimulated with 10(-7)M FMLP, O2- values (nanomoles; mean +/- SE) produced by 10(6) PMNs were 16.5 +/- 1.3 for neonatal PMNs and 12.6 +/- 0.6 for adult PMNs (p less than .02). When studied under various concentrations (10(-9) to 10(-6)M) of FMLP, neonatal PMNs produced more O2- than adult cells under the stimulation of a lower concentration (10(-8)M) as well as a higher concentration (10(-7)M) of FMLP. The increased O2- production by neonatal PMNs was also observed under their stimulation by phorbol myristate acetate. Neonatal and adult PMNs produced equal amounts of O2- when stimulated with a particulate stimulus of opsonized zymosan. To analyze further the mechanism for the increase in FMLP-induced O2- production by neonatal PMNs, we next studied whether there was some abnormality in their FMLP receptors. Neonatal PMNs had normal numbers of FMLP receptors; the receptor numbers (mean) per cell were 54,000 in neonatal PMNs and 56,000 in adult cells. Additionally, the FMLP receptors had normal affinity for the peptide. These results demonstrate that the increased production of O2- by FMLP-stimulated neonatal PMNs is not due to the abnormality of its binding to the receptors but is due to that of the subsequent events.

Adult↗

PubMed1988

Absence of circulating natural killer (NK) cells in a child with erythrophagocytic lymphohistiocytosis lacking NK cell activity.

A 5-year-old girl who was diagnosed as having erythrophagocytic lymphohistiocytosis died at age 9 years. Peripheral lymphocytes from the patient persistently lacked natural killer (NK) cell activity during the 4-year observation period: the percent lysis values as measured by a 4-hr 51Cr release assay at a 40:1 effector:target ratio were below 1.0% against K562 and Molt-4 cells as compared with the normal lymphocyte value (mean +/- SD) of 46.2% +/- 5.8% and 43.9% +/- 6.7%, respectively. The patient's lymphocytes never developed NK cell activity by their incubation with target cells for longer time periods or by their stimulation with interferon-alpha, interleukin-2, or polyinosinic-polycytidilic acid. Single cell-in-agarose assay showed the absence of target-binding cells (TBCs): TBC numbers were below 0.3% as compared with the normal lymphocyte value of 8.1% +/- 1.3% (mean +/- SD). Flow cytometry showed a marked decrease in Leu-7+ cells (1.7%) and the absence of Leu-11+ cells (0.4%) in the peripheral blood. These results first demonstrate a case of erythrophagocytic lymphohistiocytosis in which there is the lack of NK cell activity due to the absence of circulating NK cells.

Child, Preschool↗

PubMed1988

Two homozygous cases of erythrocyte pyruvate kinase (PK) deficiency in Japan: PK Sendai and PK Shinshu.

Two new erythrocyte pyruvate kinase (PK) variants with severe nonspherocytic hemolytic anemia are presented. These cases are both considered to be homozygous because of the consanguineous marriages in their parents. Their erythrocyte PK's were characterized by the recommended methods of the International Committee for Standardization in Haematology (ICSH). These two variants have been named PK Sendai and PK Shinshu. PK Sendai showed a high K0.5S (phosphoenolpyruvate), was remarkably inhibited by ATP, and was thermolabile, while PK Shinshu demonstrated remarkably low enzyme activity and required a high level of fructose 1,6-diphosphate for activation.

Adolescent↗

PubMed1988

Chondrodysplasia punctata with X;Y translocation.

We have studied a family in which the mother and her son were carriers of an X;Y translocation, der(X)t(X;Y) (p22.3;q11). The mother was of slightly short stature and had mildly short upper extremities. The son had epiphyseal punctate calcifications, mildly short extremities, a flattened nasal bridge, and mental retardation (chondrodysplasia punctata). The extra bands on the short arm of the X chromosome were identified as deriving from the long arm of the Y chromosome, using in situ hybridization with a Y-chromosome-specific DNA probe (pHY10). The chondrodysplasia punctata seen in our case may be associated with the abnormality of the distal short arm of the X chromosome caused by X;Y translocation.

Chondrodysplasia Punctata↗

PubMed1988

Facioscapulohumeral dystrophy associated with sensorineural hearing loss, tortuosity of retinal arterioles, and an early onset and rapid progression of respiratory failure.

Two sibling cases of facioscapulohumeral dystrophy (FSHD) are described. One was characterized by sensorineural hearing loss, marked tortuosity of retinal arterioles, an early onset and progression of severe restrictive-type pulmonary dysfunction, and cor pulmonale. The other had a mild course of FSHD without involvement of any other organ than muscles at the time of diagnosis. Recently, a new nosological entity of FSHD, with sensorineural hearing loss and tortuosity of retinal arterioles, was advocated. Our cases, especially the first case, seem to belong to this newly recognized entity of FSHD. Moreover, it is noteworthy that our first case exhibited rapid aggravation of severe restrictive-type respiratory failure and cor pulmonale, leading to death, which was never seen in any other reported cases.

Adolescent↗

PubMed1988

Miconazole and amphotericin B alter polymorphonuclear leukocyte functions and membrane fluidity in similar fashions.

The influence of miconazole on polymorphonuclear leukocytes (PMN) was investigated and compared with that of amphotericin B (AmB). Human PMN were preincubated in vitro with miconazole or AmB at therapeutically attainable concentrations in plasma, and their chemotactic functions were assessed with the synthetic chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (FMLP). Changes in membrane fluidity of PMN were examined by an excimer-forming lipid technique. Adherence of PMN was measured by a nylon fiber column method. Miconazole and AmB pretreatment irreversibly depressed PMN random migration and chemotaxis under agarose but did not influence superoxide anion production. Both miconazole and AmB increased PMN adherence. Miconazole and AmB lowered the binding affinity of FMLP receptors on PMN and decreased the membrane fluidity in a similar manner. These results demonstrate that miconazole and AmB alter selected in vitro membrane properties of human PMN.

Amphotericin B↗

PubMed1988

Abnormal membrane fluidity as a cause of impaired functional dynamics of chemoattractant receptors on neonatal polymorphonuclear leukocytes: lack of modulation of the receptors by a membrane fluidizer.

Membrane properties associated with chemoattractant-mediated cellular responsiveness of neonatal polymorphonuclear leukocytes (PMN) were analyzed using n-formylmethionyl-leucyl-phenylalanine. Inasmuch as aliphatic alcohols as a membrane fluidizer can enhance the chemoattractant binding and affect subsequent cellular responsiveness in adult PMN, neonatal PMN were studied for such properties by their treatment with iso-propyl alcohol, an aliphatic alcohol. The alcohol (less than 2.5%) treatment enhanced the N-formylmethionyl-leucyl-phenylalanine binding to adult PMN, but there were no changes in the N-formylmethionyl-leucyl-phenylalanine binding to neonatal PMN. Although the N-formylmethionyl-leucyl-phenylalanine-induced subsequent responsiveness including migration, lysosomal enzyme release and superoxide anion production were modulated by the alcohol treatment in adult PMN, there was no such modulation in neonatal PMN. Because membrane fluidity is largely involved in the regulation of the receptor functions, the membrane fluidity of neonatal PMN was next measured by an excimer-forming lipid technique in flow cytometry. The membrane fluidity value (0.45 +/- 0.037) of neonatal PMN was lower than that (0.74 +/- 0.072) of adult PMN (p less than 0.01). Although the aliphatic alcohol enhanced the membrane fluidity of adult PMN, it did not affect the membrane fluidity of neonatal PMN. We conclude that there is abnormal membrane fluidity as a cause of impaired functional dynamics of the chemoattractant receptors, which appears to underlie the defective modulation of cell functions by the membrane fluidizer in neonatal PMN.

1-Propanol↗