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Biomedical subjects

T Sakane

Publications and source records attributed to T Sakane.

At least 109 records · Page 6Linked to original sources
PubMed1993

Constitutive expression and production of tumor necrosis factor-beta in T-cell lines infected with HTLV-I and HTLV-II.

A highly sensitive enzyme-linked immunoassay was developed to detect soluble levels of TNF-beta. Analysis of TNF-beta in culture supernatants from long-term T-cell lines infected with human T-cell lymphotropic virus (HTLV) types I and II demonstrated elevated levels of TNF-beta when compared with uninfected T-cell lines. Presence of interleukin-2 in the culture medium showed a synergistic effect upon TNF-beta production. Further, constitutive expression of TNF-beta mRNA was observed in most cell lines infected with HTLV-I or HTLV-II. These results demonstrate that infections with HTLV-I/II can alter production of TNF-beta, presumably via the transactivation of TNF-beta promoter by the tax protein of HTLV-I and HTLV-II.

Cell Line↗
PubMed1993

Proposal of six new species in the genus Aureobacterium and transfer of Flavobacterium esteraromaticum Omelianski to the genus Aureobacterium as Aureobacterium esteraromaticum comb. nov.

Twelve strains placed in the genera Flavobacterium, Pseudomonas, and Aureobacterium, including soil isolates, were characterized taxonomically. On the basis of morphological, physiological, and chemotaxonomic data, as well as DNA-DNA hybridization data, we propose that 11 of these strains should be classified in the genus Aureobacterium as new combinations or new species, as follows: Aureobacterium esteraromaticum comb. nov. (type strain, IFO 3751 [= ATCC 8091]), Aureobacterium arabinogalactanolyticum sp. nov. (type strain, IFO 14344), Aureobacterium keratanolyticum sp. nov. (type strain, IFO 13309), Aureobacterium luteolum sp. nov. (type strain, IFO 15074 [= DMS 20143]), Aureobacterium schleiferi sp. nov. (type strain, IFO 15075 [= DMS 20489]), Aureobacterium terrae sp. nov. (type strain, IFO 15300), and Aureobacterium trichothecenolyticum sp. nov. (type strain, IFO 15077 [= JCM 1358]). Whereas the peptidoglycan type of members of this genus is considered to be B2beta, the new species A. keratanolyticum was shown to have a new peptidoglycan type, murein variation B2alpha. An emended description of the genus Aureobacterium is presented.

Bacterial Typing Techniques↗
PubMed1993

Effects of activin A on IgE synthesis and cytokine production by human peripheral mononuclear cells.

Activin A not only stimulates the synthesis and release of pituitary follicle-stimulating hormone, but exerts various effects on haematopoietic cells, embryos, and fibroblasts. In the present study we have examined effects of activin A on IgE synthesis and cytokine production by peripheral blood mononuclear cells (PBMC) in normal humans. When PBMC were cultured in the presence of IL-4, activin A significantly augmented IgE production induced by IL-4. Activin A did not affect, however, IgE production from highly purified B cells when they were stimulated with anti-CD40 MoAb and IL-4. The fact that in the latter condition IgE synthesis was T cell- and monocyte-independent indicated that activin A does not directly influence B cells for IgE synthesis. Rather, production as well as gene expression of IL-6, which is known to enhance IgE synthesis by purified monocytes, was induced by activin A alone. In addition, activin A induced other monokines such as IL-1 and tumour necrosis factor (TNF)-alpha from monocytes. In contrast, activin A neither induced nor augmented the production of TNF-beta or interferon-gamma (IFN-gamma), both of which are known to be exclusively generated by T cells. These data indicate that activin A plays a certain role in physiological functions for monocytes in normal humans.

Activins↗
PubMed1993

Tertiary and quaternary branched polyamines distributed in thermophilic Saccharococcus and Bacillus.

The distribution of long linear, tertiary and quaternary branched polyamines in twenty thermophilic Gram-positive strains belonging to the genera Saccharococcus, Bacillus or Amphibacillus were analysed by high-performance liquid chromatography and gas chromatography. The extremely thermophilic S. thermophilus contained a tertiary tetra-amine, N4-aminopropylspermidine, a linear penta-amine, thermopentamine, a tertiary penta-amine, N4-aminopropylspermine, and a quaternary penta-amine, N4-bis(amino-propyl)spermidine. N4-aminopropylspermine [NH2(CH2)3N((CH2)3NH2)(CH2)4NH(CH2)3NH2] first found in this study, was also detected in the extremely thermophilic 'B. caldolyticus' and 'B. caldotenax' and the moderately thermophilic B. stearothermophilus, B. smithii and B. thermocatenulatus.

Bacillus↗
PubMed1992

The effects of FK-506 and cyclosporin A on the proliferation of PHA-stimulated T cells in response to IL-2, IL-4 or IL-6.

Stimulated by PHA, the T cells responded well to exogenous IL-2, IL-4 or IL-6, but the responses were inhibited by FK-506 or cyclosporin A (Cs A). In contrast, when stimulated by PMA, the T cells responded to IL-2 and IL-4, but not to IL-6 and the responses were not inhibited by FK-506 and Cs A. Kinetic studies showed that FK-506 and Cs A had no inhibitory effects on T cell proliferation in response to IL-2 and IL-4 after the resting T cells were pulsed with PHA alone for a certain time. However, the response of the PHA-pulsed T cells to IL-6 was still inhibited by FK-506 or Cs A, but the inhibitory effect gradually decreased as the time in which the PHA-pulsed T cells interacted with IL-6 was prolonged. In a control system, the proliferation of the T cells that were treated with FK-506 or Cs A for 3 h and washed 3 times was not inhibited when the T cells were stimulated with PHA in combination with either IL-2, IL-4 or IL-6. Our data suggest that FK-506 and Cs A interfere with the early steps of T cell proliferation after stimulation of PHA, but not PMA. It is likely that the two drugs inhibit the expression of lymphokine receptors, by interfering Ca(2+)-related signals and that IL-6 induces T cell proliferation in a different way than IL-2 and IL-4, which are FK-506- and Cs A-sensitive.

Cells, Cultured↗
PubMed1991

Absorption and metabolic characteristics of p-aminobenzoic acid and its isomer, m-aminobenzoic acid, from the rat small intestine.

Absorption and metabolic characteristics of p-aminobenzoic acid (PABA) and m-aminobenzoic acid (MABA) from the rat small intestine were examined by means of in situ recirculation and in vitro everted sac experiments. p-Aminobenzoic acid was extremely rapidly absorbed from the rat small intestine, whereas the absorption of MABA, the m-isomer of PABA, was comparably slower. This finding was partly explained by the result that PABA is more lipophilic than MABA. The metabolite percentage of PABA was considerably greater than that of MABA in mucosal fluid, tissue, and serosal fluid. On the other hand, a concentration-dependent and a directional difference in the transfer rate of these drugs were observed in everted and noneverted sacs of rat small intestine. Furthermore, mucosal uptake of PABA or MABA was inhibited by 1 mM 2,4-dinitrophenol, 10 mM sodium azide, and pretreatment with HgCl2 (10 mM). These results indicate that MABA, as well as PABA, is transported through the intestine by a carrier-mediated transport system, and that the molecular structure of these drugs is important for their absorption and metabolic characteristics.

4-Aminobenzoic Acid↗
PubMed1991

Assessment of drug disposition in the perfused rat brain by statistical moment analysis.

Drug disposition in the brain was investigated by statistical moment analysis using an improved in situ brain perfusion technique. The right cerebral hemisphere of the rat was perfused in situ. The drug and inulin were injected into the right internal carotid artery as a rapid bolus and the venous outflow curve at the posterior facial vein was obtained. The infusion rate was adjusted to minimize the flow of perfusion fluid into the left hemisphere. The obtained disposition parameters were characteristics and considered to reflect the physicochemical properties of each drug. Antipyrine showed a small degree of initial uptake. Therefore, its apparent distribution volume (Vi) and apparent intrinsic clearance (CLint,i) were small. Diazepam showed large degrees of both influx and efflux and, thus, a large Vi. Water showed parameters intermediate between those of antipyrine and those of diazepam. Imipramine, desipramine, and propranolol showed a large CLint,i compared with those of the other drugs. The extraction ratio of propranolol significantly decreased with increasing concentrations of unlabeled propranolol in the perfusion fluid. These findings may be explained partly by the tissue binding of these drugs. In conclusion, the present method is useful for studying drug disposition in the brain.

Animals↗
PubMed1991

T cell interactions in active rheumatoid arthritis: insights from the human autologous mixed lymphocyte reaction as a model of T cell activation cascade.

The autologous mixed lymphocyte reaction (AMLR) represents the activation, proliferation and differentiation of T cells in response to signals from autologous non-T cells. Using monoclonal anti-Leu8 antibody to isolate subpopulations of human CD4+ and CD8+ T cells, we have investigated the role of these subpopulations in the T cell activation cascade during the course of AMLR. In normal subjects, CD4+Leu8+ cells are necessary for the initiation of the AMLR response, and sequentially lead to activation and proliferation of both CD4+Leu8- cells and CD8+Leu8+ cells. The activated CD8+Leu8+ cells, in turn, induce CD8+Leu8- cells to generate proliferation of the latter cells. Soluble mediators could be involved in the T cell activation cascade induced by the AMLR. Patients with active rheumatoid arthritis have a profound defect in the AMLR. Further analysis indicates that rheumatoid arthritis CD8+ T cells are markedly defective as responding cells in the AMLR. The impaired AMLR response by CD8+ cells cannot be reconstituted with AMLR-derived supernatants from normal T cells. The data suggest that the defective CD8+ T cell function may contribute to the pathogenesis of the disease.

Adult↗
PubMed1991

Transport of cephalexin to the cerebrospinal fluid directly from the nasal cavity.

The aim of the present study has been to confirm the existence of a transport pathway for a drug (cephalexin) to the cerebrospinal fluid (CSF) directly from the nasal cavity, by comparing the drug's concentrations in CSF after intranasal (i.n.), intravenous (i.v.) and intraduodenal (i.d.) administration. Higher levels of the drug were found in CSF following i.n. administration compared with the i.v. and i.d. routes, even though its plasma concentrations were similar. These findings suggest the existence of a direct transport pathway for cephalexin from the nasal cavity to the CSF. The concentration of drug in CSF at 15 min after i.n. administration was higher than that at 30 min. In contrast, its concentrations in CSF at 15 min after i.v. and i.d. administration were not significantly different from those at 30 min. The results confirm the presence of a direct transport pathway to CSF from the nasal cavity. This pathway may represent a new delivery route to CSF and possibly to brain parenchyma.

Administration, Intranasal↗
PubMed1991

The transport of a drug to the cerebrospinal fluid directly from the nasal cavity: the relation to the lipophilicity of the drug.

The objective of the present study was to clarify the relation between drug transport to the cerebrospinal fluid (CSF) from the nasal cavity and the lipophilicity of the drug using hydrophilic sulfonamides as model drugs. The nasal cavity of the rat was perfused in a single pass system and the concentrations of sulfonamides in plasma and CSF were measured. The drug concentrations in CSF and plasma after nasal perfusion were compared with those after intravenous (i.v.) administration. The drug concentrations in the CSF were remarkably high after nasal perfusion in comparison with those after i.v. administration, though the time course of the plasma concentration was not much different from that after i.v. administration. These results suggested the existence of a direct transport pathway of the sulfonamides from the nose to the CSF. In addition, the drug concentrations in the CSF increased with increasing the lipophilicity of the drugs (the partition coefficient (Pc) of the drugs between isoamyl alcohol and pH 7.4 phosphate buffer). A significant correlation was observed between the drug concentrations in CSF and Pc. In conclusion, the direct transport pathway of the sulfonamides from the nose to the CSF was confirmed and, with regard to drugs with comparatively low lipophilicity, the degree of the transport depended on its Pc.

Animals↗
PubMed1991

Impairment of lymphocyte function in patients with myelodysplastic syndrome and its correction by addition of Ca2+ ionophore and phorbol myristate acetate.

T and B cell functions were evaluated in eight patients with myelodysplastic syndrome (MDS). We studied the response to stimulation with phytohemagglutinin, concanavalin A, and anti-CD3 monoclonal antibody (OKT3 mAb), and found impairment of response in T cells from MDS patients in comparison with age-matched controls. The decreased proliferative response was not restored by combining normal T cells with monocytes from MDS patients, or by using T cells from MDS patients together with normal monocytes. Furthermore, proliferative responses in the autologous and allogenic mixed lymphocyte reactions were significantly decreased in MDS patients. B cells from MDS patients incorporated significantly less tritiated thymidine than B cells from controls when stimulated with Staphylococcus aureus Cowan I (SAC), and SAC stimulation failed to cause efficient immunoglobulin production by MDS B cells. However, T cells from MDS patients reacted normally when stimulated by phorbol myristate acetate plus a Ca2+ ionophore (ionomycin). Abnormal lymphocyte function may contribute to the failure of hematopoietic regulation and may thus play an important role in the pathogenesis of MDS. The finding that the addition of specific signals allowed the stimulation pathway to function may have important therapeutic implications.

Aged↗
PubMed1990

Effects of a novel immunosuppressive agent, FK506, on human B cell activation.

We examined the effect of new immunosuppressive agent, FK506, on the human B cell function, in comparison with that of cyclosporin A (CyA) and tried to define the discrete activation step(s) which is selectively affected by FK506 and CyA. We used polyclonal B cell activators, Staphylococcus aureus Cowan I (SAC) and pokeweed mitogen (PWM). We found that (i) the initial B cell activation process by PWM, which is on the basis of T cell-dependent manner, is susceptible to the inhibitory effects of FK506 and CyA, while initial B cell activation on the basis of T cell-independent manner by SAC is resistant to these drugs; (ii) they also inhibit helper factor production by T cells; (iii) once they are activated, the B cells become resistant to inhibition by the drugs; and (iv) on an equimolar basis, FK506 exhibits 100-fold greater inhibitory activity than does CyA. Thus FK506 mainly interferes with interactions between T cells and other cells which are essential for B cell activation process, resulting in inhibition of B cell function.

Anti-Bacterial Agents↗
PubMed1990

Anti-DNA antibody production by CD5+ and CD5- B cells of patients with systemic lupus erythematosus.

Although the presence of anti-DNA antibody is a hallmark of systemic lupus erythematosus (SLE), neither the subsets of B cells that secrete anti-DNA antibody nor the stimuli responsible for the induction of anti-DNA secretion is known. In particular, the role of CD5+ B cells in human SLE, a distinct subpopulation of antibody-secreting cells shown previously to be a source of anti-DNA antibody in murine models of SLE, is unknown. To approach these questions, we developed a sensitive enzyme-linked immunospot (ELIspot) assay to measure spontaneous secretion of antibody to single-stranded (ss) DNA, double-stranded (ds) DNA, tetanus toxoid, and polyclonal immunoglobulin (Ig) by purified CD5+ and CD5- B cells of 15 SLE patients and 15 healthy control subjects. The B cells of only 1 of 15 healthy subjects secreted a significant level of anti-ssDNA antibody, and none secreted anti-dsDNA. By contrast, in the majority of SLE patients both CD5+ and CD5- B cells secreted IgG and/or IgM anti-ssDNA as well as anti-dsDNA antibody. Further analysis of the anti-ssDNA response revealed that the level of IgG and IgM anti-DNA antibody secretion by CD5- B cells correlated closely with the level of polyclonal Ig production by the same subpopulation (r = 0.81 and 0.70, respectively). In contrast, production of anti-DNA by CD5+ B cells occurred independently of polyclonal Ig production by both CD5+ and CD5- B cell subpopulations. These results suggest that in human SLE there exist two anti-DNA antibody-producing B cell subpopulations with distinct induction mechanisms: one (CD5+), which independently secretes anti-DNA, and another (CD5-), which produces anti-DNA as an apparent consequence of polyclonal B cell activation.

Adult↗