Biomedical subjects

K Tani

Publications and source records attributed to K Tani.

At least 163 records · Page 9Linked to original sources

PubMed1997

Pharmacokinetic studies of intravenous glycosylated recombinant human granulocyte colony-stimulating factor in various hematological disorders: inverse correlation between the half-life and bone marrow myeloid cell pool.

The pharmacokinetics of an intravenous bolus dose of glycosylated recombinant human G-CSF (rhG-CSF) was examined in 15 patients with various hematological disorders and 3 normal volunteers. The elimination half-life of rhG-CSF varied with the disorder. The half-life of an initial dose of rhG-CSF (2 micrograms/weight kg) was significantly prolonged in patients with aplastic anemia (2.7 +/- 0.3 h, n = 3) and myelodysplastic syndrome-refractory anemia (2.0 +/- 0.3 h, n = 3) when compared with those in normal controls (0.9 +/- 0.5 h, n = 3). In contrast, in patients with acute myelogenous leukemia which was overt leukemia from myelodysplastic syndrome-refractory anemia with excess of blasts in transformation, the half-life was shortened after chemotherapy (0.2 +/- 0.1 h, n = 3). The half-life of rhG-CSF in 2 patients with acute lymphoblastic leukemia in complete remission was prolonged (2.0 and 2.7 h) at the time of marrow-suppression after chemotherapy and then shortened (0.5, 1.0 h, respectively) in the recovery phase. The half-life of rhG-CSF was very weakly, inversely correlated with absolute neutrophil count in blood (n = 24, r2 = 0.32, P < 0.01), and was inversely correlated with the absolute count of bone-marrow myeloid cells (nucleated cell count in bone-marrow aspirates x the percentage of myeloid cells/100) of patients with aplastic anemia and myelodysplastic syndrome-refractory anemia (n = 12, r2 = 0.63, P = 0.002). These results suggest that the half-life of intravenously administered rhG-CSF (2 micrograms/kg) reflects the size of the myeloid cell compartment in vivo, and support the hypothesis that receptor-mediated consumption mainly accounts for the clearance of exogenous G-CSF.

Adolescent↗

PubMed1997

Fatal GVHD demonstrating an involvement of respiratory muscle following donor leukocyte transfusion (DLT).

A 41-year-old female patient with AML, who relapsed after an allogeneic BMT from her HLA-identical sister, was treated by a donor leukocyte transfusion (DLT). Thereafter, bone marrow aplasia accompanied by the disappearance of leukemic blasts following the GVHD was observed. The patient died of chronic GVHD with respiratory muscle involvement 19 months after the DLT. Although the DLT was considered helpful in suppressing the proliferation of the leukemic cells, it might also have caused the severe GVHD observed in this case. Efforts to separate the lymphocyte clones responsible for GVL from those for the GVHD thus appear to be necessary for the further development of the therapeutic approach, so-called DLT.

Adult↗

PubMed1997

HIV-1-specific cell-mediated immunity is enhanced by co-inoculation of TCA3 expression plasmid with DNA vaccine.

We developed a candidate DNA vaccine designated pCMV160IIIB with pcREV (pCMV160IIIB/REV) that encodes gp160 of human immunodeficiency virus (HIV)-1IIIB and Rev driven by the cytomegalovirus (CMV) promotor. This vaccine induced both HIV-1-specific antibodies and cytotoxic T lymphocyte (CTL) activity. In the present study, we inoculated the TCA3 expression plasmid into mouse skeletal muscle with pCMV160IIIB/REV to determine whether this cytokine expression plasmid was able to modify the immune response. Results of a delayed-type hypersensitivity (DTH) assay using footpad swelling as well as those of a CTL assay clearly demonstrated that cell-mediated immunity (CMI) elicited by co-inoculation of pCMV160IIIB/REV with the TCA3 expression plasmid was markedly enhanced compared with that obtained using pCMV160IIIB/REV alone. When TCA3 expression plasmid was inoculated with anti-TCA3 antibody, enhancement of the DTH response was suppressed below the level of that obtained with pCMV160IIIB/REV alone. The titre of HIV-1-specific IgG2a was slightly high when pCMV160IIIB/REV was co-inoculated with this plasmid, suggesting that T-helper 1 (Th1) response was predominant in TCA3-inoculated mice. Infiltration of mononuclear cells was seen in the muscles at sites where TCA3 expression plasmid had been inoculated. Our present data suggest that TCA3 expression plasmid has potent adjuvant activity that results in an augmented CMI response.

AIDS Vaccines↗

PubMed1997

Inhaled low-dose nitric oxide for postoperative care in patients with congenital heart defects.

Postoperative pulmonary hypertensive crisis is a major problem that may account for a substantial part of the postoperative mortality and morbidity. We, therefore, evaluated the effect of inhalation of low-dose nitric oxide (NO) on postoperative care in pediatric patients with pulmonary hypertension. We studied 10 infants and children ages 1-108 months (median age, 11 months) with congenital heart disease associated with pulmonary hypertension. The NO and N2 gas mixture was then mixed with varied quantities of air and oxygen and delivered into a respirator instead of an inspiratory tube. Patients were treated with inhaled NO for 38.6 +/- 19.6 h (range 1-200 h). All patients were eventually weaned from high level sedation and respirator. The NO concentration ranged from 2 to 5 parts per million. During NO inhalation patients demonstrated a statistically significant reduction in systolic pulmonary arterial pressure by approximately 26%; from 55 +/- 10 to 41 +/- 20 mm Hg. Inhalation of NO resulted in a significant increase of Pao2 from 110 +/- 16 to 149 +/- 29 mm Hg. A-aDo2 significantly decreased from 284 +/- 27 to 247 +/- 31 mm Hg. In conclusion, we have shown that a low-dose NO inhalation acted as pulmonary vasodilator in patients with preexisting pulmonary hypertension.

Administration, Inhalation↗

PubMed1997

[Colonization of methicillin-resistant Staphylococcus aureus in the mouse intestinal tract].

Mice were infected intravenously with rifampicin-resistant strains selected out of methicillin-resistant Staphylococcus aureus (MRSA) strains and examined for colonization of these organisms in the intestinal tract. Three of four MRSA strains colonized in the cecum of more than 80% of the mice inoculated with approximately 10(7) cfu/mouse. The extent of colonization paralleled the lethal activity, which was inversely related to the methicillin resistivity: moderately resistant strains (MIC: 12.5 micrograms/ml) tended to show more potent pathogenicity than highly resistant ones (MIC: > or = 100 micrograms/ml). Distribution and localization of the organisms in the mice infected with a moderately resistant and highly pathogenic strain S. aureus 1-6 RFPr were studied by autobacteriography. Within one day after infection, colonies of the infecting organisms were distributed all over the body and were especially dense in the liver and spleen. On day 3, the organisms in the liver and spleen disappeared, while many colonies were observed in the intestinal tract. The organisms in the intestinal tract remained for 14 days after infection. In the autobacteriograms of the mice infected with Escherichia coli KC-14 RFPr, such persistency in the intestinal tract was not demonstrated. When viable cell counts of the cecum contents of the mice infected with S. aureus 1-6 RFPr (approximately 10(7) cfu/mouse) were made, the organisms were detected as early as 3 hr after infection and then gradually increased to more than 4 logs cfu/g on day 7. With E. coli KC-14 RFPr, a few colonies were detected transiently in the cecum contents of mice at an early stage infection, but the organisms did not increase and disappeared by day 3 after infection. These results show that the colonization in the mouse intestinal tract is a specific phenomenon to the S. aureus species including MRSA strains.

Animals↗

PubMed1997

[Direct in situ PCR method for the detection of verotoxin-producing Escherichia coli].

Rapid detection of verotoxin-producing Escherichia coli at a single-cell level under an epifluorescence microscope without culturing processes was accomplished by using the direct in situ PCR technique. We used a DNA primer set for amplification of the slt-I and slt-II genes encoding respectively verotoxin 1 and 2 (EVT and EVS primers). The bacterial cells were detected specifically by the HNPP (2-hydroxy-3-naphthoic acid-2'-phenylanilide phosphate)/Fast Red TR reaction technique. The direct in situ PCR with HNPP/Fast Red TR technique is applicable to the detection of verotoxin-producing bacteria with the slt-I or slt-II gene in not only Escherichia coli O157 but also VTEC of other serotypes.

Bacterial Toxins↗

PubMed1997

[An autobacteriographic study on distribution and localization of methicillin-resistant Staphylococcus aureus in the immunosuppressed mice].

Cyclophosphamide (CY, 250 mg/kg) was intraperitoneally administered to mice. Four days after, a rifampicin-resistant strain of methicillin-resistant Staphylococcus aureus (MRSA, S. aureus 1-6 RFPr) was intravenously inoculated at the level of 10(7) cfu/mouse. Distribution and localization of the inoculated organism were chronologically investigated by means of whole body autobacteriography. CY (100 mg/kg) was consecutively administered for 4 days following the inoculation. As a result, dense colonies of the organism were detected from many organs and tissues, that is, the liver spleen, gastrointestinal tract, kidneys, urinary bladder and bone (bone marrow) on the day after the inoculation. Following 3 days after the inoculation, the distribution and localization in CY-treated mice remained substantially unchanged and some animals died. It is demonstrated that in an experimental mouse model of MRSA infectious disease under immunosuppressed condition, the inoculated organism can stand still and proliferate not only in the gastrointestinal tract but also in the urinary tract and lymphhemopoietic organs.

Animals↗

PubMed1997

Interleukin-8 in bronchoalveolar lavage fluid of patients with diffuse panbronchiolitis or idiopathic pulmonary fibrosis.

This study was designed to clarify the contribution of IL-8 as a specific neutrophil chemotactic factor in the human respiratory tract in various pulmonary diseases. The neutrophil chemotactic activity (NCA), neutrophil counts and IL-8 concentration in the bronchoalveolar lavage fluid (BALF) obtained from normal volunteers (NV), control patients (CP), patients with diffuse panbronchiolitis (DPB) and patients with idiopathic pulmonary fibrosis (IPF) were examined. Neutrophil counts, NCA and IL-8 concentration in BALF obtained from patients with DPB or IPF was significantly higher than that from NV or CP. The IL-8 concentration correlated with neutrophil count and also correlated with NCA in BALF from patients with IPF, whereas there was no correlation between these factors in BALF from DPB. These results suggest that the contribution of IL-8 to neutrophil accumulation of the lower respiratory tract is different between IPF and DPB.

Blood Cell Count↗

PubMed1997

Thrombin stimulates platelet-derived growth factor release by alveolar macrophages in rats--significance in bleomycin-induced pulmonary fibrosis.

Thrombin is a multifunctional enzyme generated at sites of vascular injury, and is known to be increased in the lungs in some types of fibrotic lung disease. In this study, to determine whether thrombin is associated with fibroblast growth and pulmonary fibrosis in these disorders, we examined whether a growth factor for fibroblasts (platelet-derived growth factor, PDGF) was released by thrombin-stimulated alveolar macrophages (AM). The culture supernatants of rat AM stimulated with 1 or 10 U/ml of thrombin showed a significant increase in fibroblast growth-stimulating activity (FGA). Pretreatment of the AM supernatant with anti-PDGF-AA antibody significantly decreased the FGA, but pretreatment with anti-PDGF-BB antibody did not. The supernatants of AM stimulated with thrombin also increased the growth of fibroblasts from the lungs of rats with bleomycin-induced lung injury. These results indicate that thrombin stimulates AM to release PDGF-AA, which is responsible, at least in part, for fibroblast growth and the development of pulmonary fibrosis in some types of fibrotic lung disease.

Animals↗

PubMed1996

Polymorphisms of dopamine D2-like (D2, D3, and D4) receptors in schizophrenia.

The result of most association studies and linkage analyses have suggested a negative association between schizophrenia and D2-like (D2, D3, and D4) receptor polymorphisms. Although the polymorphisms of the D2-like receptor in themselves may not account for the etiology of schizophrenia, they can contribute to the severity of the symptoms. Thus, we studied the associations between the polymorphisms and their combinations, and the vulnerability of schizophrenics. Fragments of the D2-like receptor genes were amplified by means of the polymerase chain reaction, and the polymorphisms were identified by the restriction fragment length polymorphism and single-stranded conformation polymorphism methods. There were no statistically significant differences in the polymorphisms and their combinations between schizophrenics and controls. Schizophrenics with D4E1(A1/A2), which contains 2 and 1 tandem repeats of a 12-base-pair sequence in exon 1, had a lower total positive symptom score before medication than schizophrenics with D4E1(A1/A1). There was no association between the polymorphisms and negative symptoms.

Adult↗

PubMed1996

Identification of defensin-1, defensin-2, and CAP37/azurocidin as T-cell chemoattractant proteins released from interleukin-8-stimulated neutrophils.

Reports that interleukin-8 (IL-8) induces the infiltration of neutrophils followed by T-cells into injection sites led us to postulate that by stimulation of neutrophil degranulation IL-8 may cause the release of factors with chemoattractant activity for T-lymphocytes. Extracts of human neutrophil granules were chromatographed to isolate and purify T-lymphocyte chemoattractant factors. Two major peaks of T-cell chemotactic activity were purified by C18 reversed phase high pressure liquid chromatography (HPLC). The first peak was resolved further by C4 reversed phase HPLC and yielded an active fraction shown by NH2-terminal amino acid sequence analysis to contain defensins HNP-1, HNP-2, and HNP-3. Purified defensins HNP-1 and HNP-2 (kindly provided by Dr. R. I. Lehrer, UCLA) were also potent chemoattractants for human T-cells, while HNP-3 was inactive. The second peak of T-cell chemoattractant activity was also further purified to homogeneity by C4 reversed phase HPLC and identified by NH2-terminal sequence analysis as CAP37/azurocidin, a protein with sequence homology to serine proteases. 0.1 100 ng of defensins and 1.0 100 ng/ml CAP37 were able to stimulate in vitro T-cell chemotaxis. Neutrophil activating factors, i.e. IL-8, phorbol 12-myristate 13-acetate/ionomycin, and formylmethionylleucylphenylalanine each induced the release of CAP37 and defensins from neutrophil granules. Subcutaneous administration of defensins or CAP37/azurocidin into BALB/c mice resulted in a moderate neutrophil and mononuclear cell infiltrate by 4 h, which was greater by 24 h at the site of injection. Additionally, subcutaneous injection of defensins into chimeric huPBL-SCID mice resulted in significant infiltration by human CD3+ cells within 4 h. These results identify the antimicrobial proteins, CAP37/azurocidin and defensins HNP-1 and HNP-2, as potent neutrophil-derived chemoattractants for T-cells. These proteins represent primordial antimicrobial peptides which may have evolved into acute inflammatory cell-derived signals that mobilize immunocompetent T-cells and other inflammatory cells.

Amino Acid Sequence↗

PubMed1996

Treatment of leukemia with fibroblast-mediated interferon-alpha gene therapy alone or in combination with doxorubicin.

The therapeutic effects of fibroblast-mediated human interferon-alpha (IFN-alpha) gene therapy, alone or in combination with Doxorubicin (Dox), a chemotherapeutic agent, on the human leukemia-bearing nude mice were investigated. An NIH3T3 fibroblast clone (NIH3T3-IFN-alpha +) secreting the highest level of human IFN-alpha was obtained from the human IFN-alpha gene-transfected fibroblasts. Three days after i.p. Implantation of NIH3T3-IFN-alpha + cells, a certain level of human IFN-alpha could be detected in the sera from the implanted mice. After the NIH3T3-IFN-alpha + cells were implanted intraperitoneally into leukemia-bearing nude mice, the growth of leukemia was inhibited and the survival time of the leukemia-bearing mice was prolonged. The growth of leukemia was inhibited more obviously and the survival rate of the mice increased significantly when NIH3T3-IFN-alpha + cells were implanted in combination with Dox. These results demonstrate that fibroblast-mediated human IFN-alpha gene therapy is effective in treating leukemia and may achieve a better therapeutic effect when combined with Dox.

3T3 Cells↗

PubMed1996

Intact 5-HT2A receptor exons and the adjoining intron regions in schizophrenia.

Genes that regulate serotonergic (5-HT) systems may underlie the etiology of schizophrenia. In this study the gene encoding the 5-HT2A receptor in schizophrenics and healthy controls was examined. First, we sequenced all exons and the flanking introns of the 5-HT2A receptor gene in 10 schizophrenics and 10 controls. The substitution of C for T at position 102 in exon, which had been reported by Warren et al. (1993), was confirmed. Restriction fragment length polymorphism (RFLP) analysis revealed no association between polymorphism and schizophrenia. There was no association between the polymorphism and subdiagnosis, family history, age of onset, amounts of antipsychotics, or positive and negative symptoms before or after medication. Other polymorphisms in the gene were screened in 100 schizophrenics by the single-strand conformation polymorphism method, but none was found. Our results suggest that an abnormality in the 5-HT2A receptor gene in schizophrenia is unlikely.

Adult↗

PubMed1996

B-1a, B-1b and conventional B cell lymphoma from enzootic bovine leukosis.

In order to characterize the phenotypes of tumor cells and to clarify from which B cell lineage the lymphomas were derived, ten cows with enzootic bovine leukosis were examined by means of immunohistologic staining and flow cytometry. The tumor cells expressed mainly major histocompatibility complex (MHC) class II+ (10/10), BoCD11b+ (9/10), IgG1+ (8/10), B-B2+ (8/10) BoCD5+ (7/10), and lambda light chain+ (7/10). Tumor cells from only one animal expressed sIgM+ (1/10). Tumor cells from all ten animals were negative for IgG2, BoCD3, BoCD4, BoCD8, WC1-N2, and IL-2R alpha. The phenotypes of these tumor cells were all slightly different, suggesting that bovine leukemia virus (BLV)-induced lymphoma expresses phenotypic diversity. Moreover, tumor cells from seven cattle coexpressed BoCD5 and BoCD11b (B-1a cells). On the other hand, tumor cells from two of them only expressed BoCD11b (B-1b cells), and those from one were negative for both BoCD5 and BoCD11b (conventional B cells). Therefore, we concluded that BLV-induced lymphoma cells can be derived from B-1a, B-1b and conventional B cells.

Animals↗

PubMed1996

Effects of myeloid cell growth factors on alkaline phosphatase, myeloperoxidase, defensin and granulocyte colony-stimulating factor receptor mRNA expression in haemopoietic cells of normal individuals and myeloid disorders.

The mRNA expression of alkaline phosphatase (ALP), myeloperoxidase (MPO), defensin and G-CSF receptor (G-CSFR) in bone marrow cells of normal individuals and myeloid disorders, with or without in vitro stimulation by myeloid cell growth factors, i.e. G-CSF, GM-CSF and IL-3, were examined as markers for myeloid cell differentiation in both mononuclear cell (MNC) and polymorphonuclear cell (PMN) fractions. Without any stimulation, ALP mRNA was expressed only in PMNs, G-CSFR mRNA in PMNs were expressed stronger than in MNCs; both MPO and defensin mRNA were expressed to the same degree in both fractions. With stimulation, the ALP mRNA expression in both fractions was strongly enhanced by G-CSF, but the expression was inhibited by GM-CSF and/or IL-3. MPO mRNA expression was stimulated by G-CSF and/or GM-CSF in MNCs. G-CSFR mRNA expression was enhanced by G-CSF in both fractions. Defensin mRNA expression was inhibited by G-CSF. In cases of myelodysplastic syndrome and chronic myelogenous leukaemia which display a suppressed maturation of myeloid cells, our results demonstrated an almost normal response to these growth factors. Our results suggest that studies on these myeloid marker mRNA expressions would provide more knowledge about the differentiation state and cytokine reactivity of myeloid cells in normal individuals as well as various disorders.

Adult↗

PubMed1996

Cloning and sequencing of the spore germination gene of Bacillus megaterium ATCC 12872: similarities to the NaH-antiporter gene of Enterococcus hirae.

The germination mutant TM-31 of Bacillus megaterium ATCC 12872, was isolated by transposon Tn917 insertional mutagenesis. Glucose, L-proline, L-leucine and KNO3 germinated TM-31 poorly. The DNA in the region of the Tn917 insertion was cloned, and its nucleotide sequence determined. One major open reading frame was present on the cloned DNA. The hydrophobic protein encoded is presumably membrane-associated. A homology search revealed that the gene encoded in the region of the Tn917 insertion is homologous to napA of Enterococcus hirae. napA codes for the NaH-antiporter. It is hypothesized that transport of cations must play an important role in spore germination in B. megaterium ATCC 12872.

Amino Acid Sequence↗

PubMed1996

Detection of specific bacterial cells with 2-hydroxy-3-naphthoic acid-2'-phenylanilide phosphate and fast red TR in situ hybridization.

An in situ hybridization technique with HNPP (2-hydroxy-3-naphthoic acid-2'-phenylanilide phosphate) and Fast Red TR was used to detect specific bacterial cells at the single-cell level. By this technique, the fluorescent signals of target bacterial cells were up to eight times more intense than those of standard fluorescence in situ hybridization with mono-fluorescein isothiocyanate-labeled oligonucleotide probes. This novel HNPP-Fast Red TR whole-cell hybridization technique is available for the identification of small or low-rRNA-content bacterial cells in the natural environment.

Bacteria↗

PubMed1996

Cutaneous chronic graft-versus-host disease localized to the field of total lymphoid irradiation.

A 20-year-old woman with aplastic anemia underwent bone marrow transplantation from an HLA-identical sibling after total lymphoid irradiation (TLI) and cyclophosphamide (CY). The post-transplant course was uneventful. CYA was discontinued on day 221. Three weeks later, the patient developed cutaneous GVHD precisely localized to the field of TLI. No other organs were involved. Immunohistochemical staining of the affected skin was strongly positive for ICAM-1, PECAM-1 and ELAM-1; normal skin was only weakly positive for ICAM-1. CYA was restarted, and the skin lesions disappeared. TLI may contribute to an unusual presentation of cutaneous GVHD associated with specific expression of adhesion molecules.

Adult↗