Biomedical subjects

N Arai

Publications and source records attributed to N Arai.

At least 235 records · Page 13Linked to original sources

PubMed1989

Heterogeneity in terms of interleukin 4-dependent regulation of Fc epsilon...receptor/CD23 expression on chronic B-lymphocytic leukemia cells.

To discriminate the stages of maturation arrest of leukemic B cells, we have investigated the cell surface expression of Fc epsilon RII (H107 antigen) on leukemic B cells from 6 patients with chronic type B-lymphocytic leukemia (B-CLL) by a double staining method combined with cytofluorometry, and their production of soluble Fc epsilon RII by an ELISA technique. Fc epsilon RII was expressed on mu+/delta- cells of case 5 as well as on mu+/delta+ cells of cases 1, 2 and 4, but not on mu+/delta+ cells in cases 3 and 6. The cultivation of leukemic cells with IL-4 not only increased the percentage of Fc epsilon RII+ cells but also enhanced the production of soluble Fc epsilon RII+ in most cases. However, IL-4 had no effects on mu+/delta-/Fc epsilon RII+ cells of case 5, which appeared to correspond to a rather late stage of normal B cell differentiation. Moreover, while leukemic B cells from case 1 spontaneously produced large amounts of soluble Fc epsilon R, the release seemed to be inhibited by an addition of IL-4. From our observations, it is speculated that IgM+/IgD+/Fc epsilon RII- leukemic B cells express surface membrane Fc epsilon RII and produce soluble Fc epsilon RII following stimulation with IL-4, and that IgM+/IgD-/Fc epsilon RII+ B-CLL cells may exist at some late stage of B cell differentiation.

Aged↗

PubMed1989

Genetically engineered mutant of the cyanobacterium Synechococcus PCC 7942 defective in nitrate transport.

Nitrate-grown cells of Synechococcus PCC 7942 (Anacystis nidulans R2) contain a 45-kDa protein as a major protein in the cytoplasmic membrane but ammonium-grown cells lack it. A mutant (M45) was constructed by inactivating the gene encoding the 45-kDa protein. M45 did not grow under low concentrations of nitrate but high concentrations of nitrate could support its growth, with the optimal concentration being 40-70 mM. The growth rate of M45 was as high as that of the wild-type cells when ammonium was the nitrogen source. The 45-kDa protein was absent in M45 irrespective of the growth conditions. The activities of nitrate and nitrite reductases were higher in M45 than in wild type. The rate of nitrate-dependent O(2) evolution in wild type measured in the presence of L-methionine D,L-sulfoximine and D,L-glyceraldehyde showed saturation kinetics with respect to nitrate concentration in the external medium. The nitrate concentration required to produce half the maximal rate was 1 muM. In M45, the rate of nitrate-dependent O(2) evolution was nearly zero at nitrate concentrations <1 mM and was linearly increased as the concentration increased. The presumed absence of nitrate transport in M45 demonstrated by these results suggested that the 45-kDa protein is a nitrate transporter.

Journal Article↗

PubMed1989

Preferential differentiation of inflammatory cells by recombinant human interleukins.

The effects of recombinant human interleukins (IL) on hematopoiesis were explored by using suspension cultures of mononuclear cells of human umbilical cord blood and bone marrow cells. The results showed that IL-5 induced the selective differentiation and proliferation of eosinophils. After 3 weeks in culture with IL-5, over 90% of nonadherent cells in both bone marrow cell and cord blood cell cultures became eosinophilic myelocytes. Culture of the same cells with IL-4 resulted in the selective growth of OKT-3+ lymphocytes. In suspension cultures of bone marrow cells and cord blood cells grown in the presence of IL-3, basophilic, eosinophilic, and neutrophilic myelocytes developed within 2 weeks. By 3 weeks, however, the majority of non-adherent cells became eosinophilic myelocytes. In contrast to mouse bone marrow cell cultures, neither IL-3 nor combination of IL-3 and IL-4 induced the differentiation of mast cells in human bone marrow or cord blood cell cultures.

Basophils↗

PubMed1989

[In vitro study of bacterial invasion in radicular dentin].

The purpose of this study was to investigate whether plaque bacteria invade exposed radicular dentin after root planing or chemical root treatment in vitro. Pieces of dentin were cut out from impacted third molars. The surface of all dentin pieces was treated with sandpaper (#240) so as to make the surface roughness of dentin pieces equal to that of the root surface after root planing (RP surface). Half of the dentin pieces were treated with citric acid (pH 1.0) for 3 minutes (CA surface). After sterilization, each dentin piece was incubated at 37 degrees C in a culture medium inoculated with either S. mutans or S. sanguis. After 1, 3, 7 and 28 days of incubation, the invasion of microorganisms into the dentinal tubules was histologically examined using a light microscope. The following results were obtained. 1. The invasion of S. mutans and S. sanguis into the dentinal tubules was observed at 1, 3, 7 and 28 days. The depth and number of bacterial invasion into the dentinal tubules were positively correlated with incubation time on CA surfaces but not with RP surfaces. 2. The depth and the number of bacterial invasion into the dentinal tubules were higher on the CA surfaces than the RP surfaces. 3. Since the citric acid treatment of scaled and root planed root surfaces may accelerate bacterial invasion from treated root surfaces, the use of citric acid might be harmful in patients with inadequate plaque control.

Dental Plaque↗

PubMed1989

[In vivo study of bacterial invasion in root planed and citric acid treated radicular surfaces of periodontally involved human teeth].

The purpose of this study was to investigate whether plaque bacteria invade the exposed radicular dentin after root planing or chemical root treatment in vivo. Eighteen caries-free human periodontally involved teeth with hopeless prognoses were studied. Fourteen teeth were scaled and root planed with hand curette type scalers. The proximal surface of each treated tooth was designated as the RP surface. The remaining half of the proximal surface was treated with citric acid (pH 1.0) for 3 minutes and was designated as the CA surface. Four untreated teeth served as controls. After 4 weeks, the teeth were extracted, and were processed for light microscopy and for scanning electron microscopy concerning bacterial invasion into the supragingival radicular dentin. The following results were obtained. 1. Radicular cementum was present on most untreated tooth surfaces. However, bacteria were never seen in the dentinal tubules. 2. Bacterial invasion into the dentinal tubules was observed in five of the 10 proximal surfaces (50% of the RP surfaces) and in nine of the 10 proximal surfaces (90% of the CA surfaces). 3. The depth (9.5 +/- 24.1 microns vs 84.6 +/- 136.3 microns) and percentage (0.8 +/- 2.1% vs 20.3 +/- 17.3%) of bacterial invasion in the dentinal tubules of the RP surfaces was lower than that of the CA surfaces. 4. Cocci and short rods were present in the supragingival dentinal tubules. 5. Since CA surfaces may accelerate bacterial invasion the citric acid treatment might be harmful in patients with inadequate plaque control.

Citrates↗

PubMed1989

[Study of infective complications in elderly patients with leukemia].

Elderly patients (more than 60 years old, n = 45) with leukemia who presented from 1976 to June 1987 were studied. Twenty-two were classified as the typical type and 23 were the atypical type (hypoplastic n = 10, low percentage n = 13) from the bone marrow findings at the time of diagnosis, among these 45 patients 102 infections, 48 of which occurred in patients with typical type leukemia, 31 infections occurred in hypoplastic leukemia and 23 in low percentage leukemia. Respiratory infections were the most common, regardless of the type of leukemia. The following pathogens, the majority of them were gram negative bacteria, were isolated before the administration of antimicrobial agents. Thirty infections were caused by multiple pathogens (typical 14, hypoplastic 10, low percentage 6). Of those 40% were caused by gram negative pathogens, 30% were due to both gram negative and positive pathogens. The causes of death in 37 patients included bleeding (n = 150 and infections (n = 13). Typical leukemia (n = 8) was the most common among patients who died of infection.

Aged↗

PubMed1989

Humoral regulation of eosinophilopoiesis in vitro: analysis of the targets of interleukin-3, granulocyte/macrophage colony-stimulating factor (GM-CSF), and interleukin-5.

In order to delineate the humoral regulation of eosinophil production, we studied the effects of interleukin-3 (IL-3), granulocyte/macrophage colony-stimulating factor (GM-CSF), and interleukin-5 (IL-5), and their combinations on eosinophil colony formation in clonal cell culture. We plated 1,000 bone marrow null cells per dish and in some experiments used polyclonal anti-gibbon IL-3 sera and anti-human GM-CSF. IL-3 or GM-CSF independently from each other supported eosinophil colony formation. Although IL-5 supported formation of small eosinophil colonies, the number of colonies were significantly smaller than that supported by GM-CSF or IL-3. Cytological examination of the constituent cells revealed that some of the apparent eosinophil colonies supported by IL-3 and GM-CSF were mixed colonies containing eosinophils and one or more other lineages. In addition, the majority of the eosinophils seen in cultures with IL-3 and/or GM-CSF proved to be early eosinophil precursors including eosinophilic promyelocytes, myelocytes, and meta-myelocytes. IL-5-supported eosinophil colonies were pure eosinophil colonies and contained mostly maturer eosinophils such as band and segmented forms. These observations indicated that the developmental stages of the targets of IL-3 and GM-CSF are earlier than those of IL-5 and that the primary function of IL-5 is to support terminal maturation of eosinophils.

Adult↗

PubMed1989

Ultrastructure of eosinophils and basophils stimulated to develop in human cord blood mononuclear cell cultures containing recombinant human interleukin-5 or interleukin-3.

We used recombinant human interleukins (IL) and cultured human cord mononuclear cells to determine the cell lineages supported by the inclusion of the individual interleukins-5, -3, or -4 in the cultured media. Cultures were examined by electron microscopy at 2-, 3-, and 5-week culture intervals. We found that IL-5 primarily supported the eosinophilic lineage with lesser numbers of basophils, that IL-3 initially supported all granulocyte lineages but eventually supported the eosinophilic lineage with lesser numbers of basophils, and that IL-4 did not support the development of granulocyte lineages in these cultures. At early culture intervals in either IL-5 or IL-3, eosinophilic and basophilic myelocytes were seen in variable proportions. Mature cells of these lineages developed later. Both mature eosinophils and basophils showed morphologic evidence of activation similar to those described for tissue eosinophils and basophils in various disorders. Mast cells were absent in all cultures. Recognition of the variable morphologies associated with maturation and activation of human eosinophils and basophils is important for the correct identification of cell lineages that develop in cultures containing human recombinant interleukins.

Basophils↗

PubMed1989

[Iron deposition in the brain of a case of the special type of hepatocerebral encephalopathy].

The histochemical demonstration of iron and the iron content was examined in the brain of a case of the special type of hepatocerebral encephalopathy (HCE). The patient had suffered from a liver disease since 36 years old. At 44 years old, she experienced the first attack of twilight state with flapping tremor. She had predilection for eating beans. Her personality gradually became euphoric with the recurrent episodes of unconsciousness. At 54 years old, she died of the complication of melena, renal insufficiency and pneumonia. The liver showed cirrhotic changes and iron content of liver was 0 or 1 after MacDonald's criterion scale. The histopathological findings of the brain showed the characteristic changes of HCE, which were incomplete softening and spongy state pseudolaminarilly extending in the deep layer of the cerebral cortex, the proliferation of the severely changed Alzheimer 2 type glia with or without intranuclear carmine positive substance. The deparaffinized sections, 20 mu in thickness, which were not fastened on slides were used for the histochemical study of iron, because iron deposits displaced inside of the brain tissues when the paraffin sections were fastened on slide glasses in the constant-temperature bath. The iron deposition was found in the central gyrus, superior temporal gyrus, medial and lateral occipito-temporal gyrus and middle temporal gyrus of occipital lobe. The iron accumulated in the ground substance, glia cell bodies, glia nuclei and unknown bodies in the 3-6 layers of cerebral cortex of these gyri. The iron accumulation demonstrated histochemically in other parts of the brain were group 1, 2 by Spatz, mammillary body, glia cell bodies in cerebellar white matter and pons.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain↗

PubMed1988

Participation of IL-4 in the formation of IgD-binding factors by antigen-primed mouse spleen cells.

BALB/c mouse spleen cells primed with either keyhole limpet hemocyanin or DNP-keyhole limpet hemocyanin formed not only IgG-binding factors (BF) and IgE-BF but also IgD-BF upon antigenic stimulation. Analysis of cellular mechanisms involved in the formation of Ig-BF by antigenic stimulation revealed that Ag-primed Th cells released lymphokines upon antigenic stimulation, and that the lymphokine(s) in turn stimulates unprimed T cells to form Ig-BF. Normal unprimed lymphocytes formed IgD-BF upon incubation with culture supernatants of Ag-stimulated spleen cells. The formation of IgD-BF induced by the culture supernatant was prevented by anti-IL-4 mAb (11B11). It was also found that 0.3 to 10 U/ml mouse rIL-4, but none of the rIL-1, IL-2, and IFN-gamma, induced normal T cells to form IgD-BF. Indeed, both IL-2 and IFN-gamma inhibited IL-4 to induce the formation of IgD-BF. In contrast, 10 to 50 U/ml of IFN-gamma induced the formation of IgE-BF, and 50 to 200 U/ml IFN-gamma induced the formation of IgG-BF. However, none of the other lymphokines tested, i.e., IL-1, IL-2, and IL-4, induced the formation of either IgE-BF or IgG-BF. The IgD-BF formed by antigenic stimulation of keyhole limpet hemocyanin-primed spleen cells and those formed by stimulation of normal lymphocytes with 1 to 2 U/ml IL-4 enhanced both IgM and IgG1 plaque-forming cell responses of SRBC-primed spleen cells to homologous Ag. In contrast, 1 to 2 U/ml of IL-4, which could induce the formation of IgD-BF, failed to affect the PFC responses. It appears that the formation of IgD-BF may be involved in the effects of IL-4 to enhance the antibody response.

Animals↗

PubMed1988

Isolation and characterization of multiple variants of recombinant human interleukin 4 expressed in mammalian cells.

We have purified recombinant human interleukin 4 (huIL-4), formerly named B-cell stimulatory factor-1, from supernatants of COS-7 monkey kidney and L-929 cells transfected with the cDNA for huIL-4. The purified protein exhibited a specific activity of 2.6 X 10(7) units/mg in a T-cell proliferation assay and consisted of multiple components on sodium dodecyl sulfate-polyacrylamide gel electrophoresis exhibiting Mr values of 15,000, 18,000, and 19,000. All forms of huIL-4 eluted on gel filtration chromatography with an apparent Mr of 22,000. Gas-phase microsequencing identified 26 and 8 amino acid residues at the N and C termini, respectively, all of which were consistent with the cDNA sequence. The site of processing of the signal sequence was found to occur between Gly-24 and His-25. Incubation with N-glycanase converted the 18- and 19-kDa variants to a 15-kDa form. Treatment with endo-beta-N-acetylglucosaminidase H reduced the molecular mass of the 18-kDa variant to 15 kDa, but did not have any apparent effects on the mass of the 19-kDa species. The removal of oligosaccharide by any of these treatments did not affect bioactivity in the T-cell proliferation assay. Neither O-glycanase nor endo-beta-N-acetylglucosaminidase D affected the molecular weight of any of these species. These data suggest that differences in carbohydrate structure account, at least in part, for the observed microheterogeneity.

Amino Acid Sequence↗

PubMed1988

The AKR thymoma BW5147 is able to produce lymphokines when stimulated with calcium ionophore and phorbol ester.

We produced the T cell hybridoma D9C1.12.17 by fusing an IL-4-producing T cell clone D9.1Hi with the AKR thymoma BW5147. The resulting hybridoma produced IL-2 as well as IL-4 even though none of the parental cells produced IL-2 after stimulation with Con A. The production of IL-2 was confirmed at the mRNA level by using an S1 nuclease protection assay. Further analysis indicated that Con A-induced IL-2 production was a common phenomenon among T cell hybridomas derived from this fusion. Although BW5147 does not produce detectable lymphokines after Con A stimulation, this line was able to produce IL-2, granulocyte-macrophage colony stimulating factor, and small amounts of IL-3 and IFN-gamma when stimulated with calcium ionophore and phorbol ester. The latter agents are thought to mimic the activating signal(s) delivered through the Ag:MHC TCR. This observation indicates that BW5147 has the ability to produce lymphokines but may lack component(s) which couple the extracellular signal to lymphokine production, and suggests that in T cell hybridomas, part of the spectrum of lymphokines produced may be contributed by BW5147.

Animals↗

PubMed1988

Expression of high affinity receptors for murine interleukin 4 (BSF-1) on hemopoietic and nonhemopoietic cells.

In this report a method for the affinity purification and radiolabeling of recombinant mouse interleukin (IL)-4 is described. It is shown on the basis of several criteria that IL-4 retains full biologic activity after radioiodination and can therefore be used as a valid model for measuring the binding characteristics of native IL-4. By using Scatchard plot analysis of equilibrium binding data, it is demonstrated that 125I-IL-4 binds to a high affinity cell surface receptor which is expressed by both hemopoietic and nonhemopoietic cells. The dissociation constant for 125I-IL-4 (Kd = 20 to 60 pM) corresponds to the concentration of IL-4 which gives 50% biologic activity (i.e., 10 to 30 pM). Binding of 125I-IL-4 is rapid (t1/2 of 2 min), whereas dissociation occurs at a slow rate (t1/2 approximately 4 hr). The IL-4 receptor shows a high degree of specificity. Whereas unlabeled mouse IL-4 competed with mouse 125I-IL-4 in an equimolar fashion for binding to IL-4 receptors, several other lymphokines, including mouse IL-2, IL-3, interferon-gamma, granulocyte-macrophage colony-stimulating factor, and human IL-1, IL-2, and IL-4 were unable to inhibit, even at molar excesses of 400 to 800-fold. At 37 degrees C, 125I-IL-4 is rapidly internalized (approximately 200 molecules/cell/min) by HT-2 cells, with at least 85% of cell surface receptors being functional in this respect. Receptors for IL-4 were found to be expressed by subclasses of T and B cells, mast cells, macrophages, and by cells of the myeloid and erythroid lineages. This wide distribution of receptor expression closely matches the known spectrum of biologic activities of IL-4, including proliferation and/or differentiation of T and B cells, mast cells and granulocytes, and induction of macrophage antigen-presenting capacity. IL-4 receptors were also found on a variety of nonhemopoietic cells such as cloned stromal cell lines from the bone marrow, spleen, thymus, and brain, and on muscle, brain, melanoma, fibroblast, and liver cells. Indeed, only 5 of more than 90 cell types tested have undetectable numbers of IL-4 receptors. The biologic effects of IL-4 on nonhemopoietic cells have not yet been reported and await elucidation.

Animals↗

PubMed1988

Human DNA polymerase alpha gene expression is cell proliferation dependent and its primary structure is similar to both prokaryotic and eukaryotic replicative DNA polymerases.

We have isolated cDNA clones encoding the human DNA polymerase alpha catalytic polypeptide. Studies of the human DNA polymerase alpha steady-state mRNA levels in quiescent cells stimulated to proliferate, or normal cells compared to transformed cells, demonstrate that the polymerase alpha mRNA, like its enzymatic activity and de novo protein synthesis, positively correlates with cell proliferation and transformation. Analysis of the deduced 1462-amino-acid sequence reveals six regions of striking similarity to yeast DNA polymerase I and DNA polymerases of bacteriophages T4 and phi 29, herpes family viruses, vaccinia virus and adenovirus. Three of these conserved regions appear to comprise the functional active site required for deoxynucleotide interaction. Two putative DNA interacting domains are also identified.

Amino Acid Sequence↗

PubMed1988

Foamy spheroid bodies in the substantia nigra. Report of an unusual case with recurrent attacks of peculiar twilight state.

An unusual case of recurrent attacks of peculiar twilight state persisting for 41 years is the subject of this clinicopathological report. During the attacks the patient had depersonalization, showing a stiff face, and the electroencephalogram showed constant 5 Hz diffuse theta waves. The unique and characteristic neuropathological finding were many foamy spheroid bodies (FSB) in the substantia nigra which sometimes contained varying numbers of fine or coarse eosinophilic granules. Ultrastructurally, the FSB contained various small electron-dense granules and/or membranous structures quite different from so-called spheroids (axonal swellings). Bodian staining demonstrated that some FSB were situated within the bundles of the neuronal processes, suggesting that the FSB has originated from the degeneration of the axon and/or dendrites in the substantia nigra.

Aged↗

PubMed1988

An ovarian Sertoli-Leydig cell tumor with heterologous mucinous gland and NSE-immunoreactive-cell.

A rare case of ovarian Sertoli-Leydig cell tumor with heterologous mucinous glands and tiny carcinoid-like foci in a 33-year-old female is reported. In addition to these heterologous elements, peculiar cells, which were oval, eosinophilic and neuron-specific enolase (NSE)-positive, were also observed and had not been described previously. These NSE-immuno-reactive cells were different from argentaffin cells observed in mucinous glands and carcinoid-like foci, and seemed to play a significant role in the appearance of the heterologous mucinous gland. The nature of this peculiar NSE-immunoreactive cell is discussed.

Adult↗

PubMed1988

Three categories of the degenerative appearance of the human cerebellar dentate nucleus. A morphometric and morphological study.

This morphometric and morphological study demonstrates 3 categories (types A, B and C) of degenerative feature in the cerebellar dentate nucleus. Type A is characterized by neuronal loss, astrocytosis and granular and/or amorphous argyrophilic change around the neurons and neuronal processes, and this type was thought to be synonymous with the so-called grumose degeneration of the DN. Type B is characterized by extensive neuronal loss and astrocytosis without argyrophilic change, and it was considered that many diverse factors were responsible for type B. Type C features marked swelling of the neurons without neuronal loss, astrocytosis or argyrophilic change. The Purkinje cells were not involved in type A and C, but severely damaged in type B. Clinically, type A was observed in progressive supranuclear palsy and dentatorubropallidoluysian atrophy, type B extensively in many diseases including anoxic, toxic and infectious disorders, and type C in tardive dyskinesia manifesting with oral hyperkinesia. Types A and C may be more or less specific signs of degeneration of the dentate nucleus, whereas type B appears to be non-specific.

Adult↗

PubMed1988

IgE production by normal human lymphocytes is induced by interleukin 4 and suppressed by interferons gamma and alpha and prostaglandin E2.

The effect of human recombinant interleukin 4 (IL-4) on antibody production by normal peripheral blood mononuclear cells enriched for B cells was investigated. IL-4 preferentially induced IgE synthesis in vitro. In addition, a low induction of IgG production was observed, whereas IL-4 had no effect on IgA and IgM synthesis. The IL-4-induced IgE production by B cells required T cells and monocytes but was specifically inhibited by an anti-IL-4 antiserum indicating that, although IL-4 acts indirectly, it is responsible for the induction of IgE synthesis. IL-4-induced IgE production was blocked in a dose-dependent way by interferon gamma (IFN-gamma), interferon alpha (IFN-alpha), and prostaglandin E2. IFN-gamma also inhibited IL-4-induced IgG production. These inhibitory effects of IFN-gamma and IFN-alpha on IgE production cannot be attributed to toxic effects since IFN-alpha induced IgM production in the presence of IL-4, whereas IFN-gamma was ineffective in inhibiting IgG production induced by IL-2. IFN-gamma, IFN-alpha, and prostaglandin E2 also inhibited IL-4-induced expression of the low-affinity receptor for the Fc portion of IgE (CD23) on B cells, indicating that there is an association between CD23 expression and IL-4-induced IgE production. This theory was supported by the finding that IL-4-induced IgE production was inhibited by F(ab')2 fragments of an anti-CD23 monoclonal antibody.

Antibodies, Monoclonal↗