Biomedical subjects

Y Ochi

Publications and source records attributed to Y Ochi.

At least 73 records · Page 4Linked to original sources

PubMed1994

Analysis of IL-2 gene regulation in c-fos transgenic mice. Evidence for an enhancement of IL-2 expression in splenic T cells stimulated via TCR/CD3 complex.

Effects of the deregulated c-fos gene product on IL-2 expression were studied in splenic T cells from c-fos transgenic (H2-c-fos) mice. IL-2 gene expression and IL-2 production by H2-c-fos T cells stimulated with immobilized anti-CD3 Abs were enhanced and prolonged as compared with those by control T cells. Activator protein-1 activity in nuclear extract from the H2-c-fos T cells was also higher than that from the control cells. There was no significant difference in the activity of other transcription factors including IL-2 kappa B, NFAT, and Oct-1, between the H2-c-fos and the control T cells. However, activity of a negative regulatory element binding factor (NRE-A) in the H2-c-fos T cells was much lower than that in the control cells. These results suggest that c-Fos/activator protein-1 is a major regulatory factor for IL-2 gene expression in splenic T cells activated through the TCR/CD3 complex.

Animals↗

PubMed1994

Kinetic modelling of liposome degradation in serum: effect of size and concentration of liposomes in vitro.

The purpose of this study is to propose a new method for quantitative evaluation of liposome degradation in serum. The time course of liposome degradation in rat serum was monitored continuously, using 6(5)-carboxyfluorescein as an aqueous phase marker. The degradation curves exhibited three characteristic phases: lag time, degradation, and plateau. This curve was described by a kinetic model with three parameters: lag time (tau), first-order degradation rate constant (k), and maximum degradation (alpha). The rate and extent of the degradation of liposomes were evaluated separately in terms of k and alpha, respectively. The effects of size and concentration of liposomes on their degradation kinetics were examined using this method. Both k and alpha increased with increasing liposomal size. The increased affinity of larger liposomes for complement was suggested to increase both k and alpha. On the other hand, alpha decreased with increasing liposomal concentration without altering k. The decreased extent of degradation was considered to result from the depletion of complement components. There was no significant effect of size and concentration of liposomes on tau. Quantitative evaluation of the rate and extent of degradation of liposomes will provide deeper insights into the interaction between liposomes and serum components, and basic information on liposomes as potential drug carriers.

Animals↗

PubMed1994

Adamantane as a brain-directed drug carrier for poorly absorbed drug. 2. AZT derivatives conjugated with the 1-adamantane moiety.

Five AZT (azidothymidine) prodrugs conjugated with the 1-adamantane moiety via an ester bond were synthesized to improve the transport of AZT into the central nervous system (CNS). In in vitro degradation studies with rat and human plasma, it was demonstrated that the prodrugs were degraded enzymatically and converted quantitatively to their parent drug. AZT. As assessed by octanol-buffer partitioning, the prodrugs were much more lipophilic than AZT and were expected to penetrate the blood-brain barrier (BBB) readily. In in vivo studies, in which the prodrugs were administered intravenously to rat, the prodrugs in brain tissue were detected at 7-18 times higher concentrations than AZT in spite of the negligible amount of the prodrug in the cerebrospinal fluid. These results indicate that the introduction to AZT of the 1-adamantane moiety results in the enhancement of the BBB penetration. This pharmaceutical approach would be beneficial for the efficient treatment of the CNS infection by human immunodeficiency virus.

Adamantane↗

PubMed1994

Deregulated expression of c-fos disturbs proliferative responses of B cells to sIg cross-linking.

B cell activation by surface immunoglobulin (sIg) cross-linking is accompanied by transient expression of the c-fos protooncogene. This expression is strictly controlled in the B cells. To investigate a biological implication of the c-fos expression in the process of B cell activation by sIg cross-linking, we examined the proliferation of splenic B cells from H2-c-fos transgenic mice. Constitutive expression of the c-fos gene perturbs de novo synthesis of RNA and DNA in the B cells stimulated with anti-IgM antibody. Early events of signal transduction such as an increase in intracellular free calcium level and an induction of the endogenous immediate early genes (c-fos and c-myc) were apparently intact in those B cells. When the sIg stimulation of B cells was mimicked by the costimulation with 12-O-tetradecanoylphorbol 13-acetate and ionomycin, H2-c-fos B cells required higher concentrations of ionomycin for the optimal proliferative responses, suggesting that calcium-dependent signal transduction pathways are disturbed in those B cells. These results demonstrate a novel regulatory effect of c-fos protein on the proliferation of B cells mediated by sIg cross-linking.

Animals↗

PubMed1994

Production of thyroid stimulation blocking antibody without TSH receptor binding activity in rabbits with experimental autoimmune thyroiditis.

When rabbits were immunized with porcine thyroid plasma membrane, some cases of produced antibodies showed the blocking activity for TSH stimulated cAMP production in cultured porcine thyroid cells in spite of negative TSH binding inhibitory immunoglobulin (TBII) activity. The inhibitory effect of these thyroid stimulation blocking antibodies (TSBAbs) on cAMP increase by forskolin and GTP gamma S in porcine thyroid cells was observed in 1 and 3 rabbits, respectively. When the blocking activity of these antibodies for stimulated cAMP production by forskolin, GTP gamma S and NaF was examined in the isolated porcine thyroid membrane, no blocking activity for these 3 stimulators except in 1 case was found. The blocking activity of these antibodies could be absorbed significantly by incubation with porcine thyroid plasma membrane as antigen. The blocking activity was not observed in rabbits immunized with porcine thyroglobulin. The present experiment demonstrated that the produced antibody in rabbits against porcine thyroid membrane had the blocking activity for TSH stimulation to thyroid cells without affecting TSH binding to its receptor. These facts suggest that this type of blocking antibody may be produced against any antigen of thyroid membrane origin except the TSH receptor.

Adenylyl Cyclases↗

PubMed1994

Studies on the action of thyroid stimulation blocking antibody (TSBAb) on thyroid cell membrane.

The effect of thyroid stimulation blocking antibody (TSBAb) on stimulated cyclic AMP (cAMP) production induced by adenylate cyclase stimulators in porcine thyroid membrane (PTM) and porcine thyroid cells (PTC) has been studied. Ten TSBAbs with high TSH binding inhibitory immunoglobulin (TBII) activities significantly blocked TSH-stimulated cAMP production in PTC. The blocking effect of TSBAb on the cAMP increase induced by forskolin or GTP-gamma S stimulation in PTC was found in a few cases. However, there was no blocking action of TSBAb on the cAMP increase stimulated by forskolin, GTP gamma S, or NaF in isolated PTM. When TSBAb-globulin was absorbed with PTM or guinea pig epididymal fat membrane (GPFM), the TBII activity in TSBAb-globulin was significantly absorbed by these membranes. A decrease of TSBAb activity (blocking activity for TSH-stimulated cAMP production in PTC) by PTM absorption, but no decrease by GPFM absorption, was found in six cases. This suggests that the potent TSBAb-neutralizing component may be associated with a non-TSH receptor site in the thyroid membrane. The other four cases showed a decrease of TSBAb activity by absorption with both PTM and GPFM. This suggests that the TSBAb-neutralizing activity may be associated with the TSH receptor site of both PTM and GPFM. The results of the present study suggest that TSBAb may block TSH action either via the TSH receptor itself or via a non-TSH receptor component of the thyroid membrane and not at a postreceptor level.

Animals↗

PubMed1994

Characteristics of aspartate aminotransferase binding immunoglobulin determined by the isotope method.

A woman who had no known underlying diseases showed a persistent elevation (about 300 U/L) of serum aspartate aminotransferase (AST) without other abnormal laboratory findings. Cellolose gel electrophoresis showed that the AST activity in the patient had an atypical band with slower mobility than normal AST. When the sera from the patient and from a patient with acute hepatitis were mixed, the atypical band increased in density and the band of normal size AST disappeared. When the serum was fractionated on Sephadex G-200 gel filtration medium, almost all AST activity was found between the void volume and the gamma-globulin fraction. However, the AST activity in this fraction was not retained on dissociation into small AST by acid treatment. This suggests the loss of enzyme activity in dissociated small AST. The patient's serum was then incubated with iodine 125-labeled porcine AST; when this was fractionated on gel filtration medium, the main radioactivity was eluted in the void volume fraction. The binding activity for 125I-porcine AST was found in the gamma-globulin fraction obtained by gel filtration. The affinity constant of 125I-porcine AST binding to the gamma-globulin fraction was 1.0 x 10(-8) mol/L by Scatchard analysis. The binding gamma-globulin appeared to be (polyclonal) IgG, and the binding site was located in F(ab')2 and Fab fragments. The IgG could be bound with both human and porcine AST but not with chick AST. Thus the IgG appears specific for AST of mammalian species.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

[A study of pacemaker implantation to cases performed valve surgery].

For 13 years between 1980 and 1992, 23 patients needed pacemaker (PM) implantation because of bradyarrhythmia, 21 of atrial fibrillation and two of complete A-V block, after valve surgery. Five of 88 survivors (5.7%) after OMC, 11 of 227 (4.8%) after MVR, one of 169 (0.6%) after AVR, five of 67 (7.4%) after MVR + AVR and one of 15 (6.7%) after TVR underwent PM implantation in postoperative period. Two cases who had heart failure was implanted PM in early postoperative period. In late period, the mean duration between previous valve surgery and PM implantation was 6.4 years in 12 cases after initial valve surgery and 2.3 years in nine after second valve surgery. Postoperative course after PM implantation was almost good, but one case was died due to critical arrhythmia. And one case underwent re-MVR because of mitral bioprosthesis dysfunction and one, without anticoagulant after OMC, was complicated cerebral infarction.

Adult↗

PubMed1993

Inhibition of experimental metastasis by an alpha-glucosidase inhibitor, 1,6-epi-cyclophellitol.

Isolated from a culture filtrate of Phellinus sp., cyclophellitol is a specific inhibitor of beta-glucosidase, but unlike castanospermine, it does not inhibit experimental metastasis. However, its structural analogue, 1,6-epi-cyclophellitol, inhibited alpha-glucosidase as well as beta-glucosidase, and inhibited experimental metastasis. 1,6-Epi-cyclophellitol depressed alpha-glucosidase activity in cultured B16/F10 cells after 48 h of incubation. Preincubation of B16/F10 cells for 48 h with 1,6-epi-cyclophellitol inhibited invasion of the cells in a Boyden chamber assay at the doses effective in inhibiting alpha-glucosidase in situ. Pulmonary metastasis of B16/F10 cells in mice was inhibited by pretreatment of the cells with 1,6-epi-cyclophellitol in culture. The inhibitor reduced the collagen type I- and IV-mediated attachment of the cells, whereas it had no effect on laminin-mediated attachment. These results suggest that alpha-glucosidase in tumor cells is essential for the metastatic process through the cellular interaction with collagen type I and IV.

Animals↗

PubMed1993

Stimulatory action of pituitary adenylate cyclase-activating polypeptide (PACAP) on thyroid gland.

PACAP 27 and 38 (27 and 38 amino acids, respectively) increased rapidly cAMP production in porcine thyroid cells in vitro. Both PACAPs also increased T4 production from mouse thyroid in vivo similar to TSH. Both PACAPs (especially 38) inhibited the binding of 125I-labeled TSH to thyroid membrane in the medium containing bovine serum albumin. This inhibitory action remarkably decreased in the medium containing normal human serum. Decrease of inhibition of TSH binding by serum containing PACAP could not be explained simply by proteolytic destruction of PACAP, although the labeled PACAP (especially 38) was destructed by proteases in thyroid membrane or human serum. These facts showed that PACAP had the thyroid stimulating action and the inhibitory action on the binding of TSH to thyroid receptor.

Animals↗

PubMed1993

[Anti/TSH antibodies in thyroidal diseases].

The negative values in the assay for TSH receptor antibody (TRAb) led to the discovery of TSH binding antibody. The existence of anti-TSH antibodies have been reported mainly in Graves' disease and other thyroidal diseases (Hashimoto's thyroiditis, silent thyroiditis and subacute thyroiditis). Some reports suggest that the TRAb in Graves' disease may be an anti-idiotype antibody against an anti-TSH antibody, or that anti-TSH antibodies may be anti-idiotype antibodies against TRAb. However, TSH binding of TSH binding antibody was not inhibited by TRAb. These TSH binding antibodies showed a reaction in several mammalian species except humans. We demonstrated that almost all TSH binding antibodies reacted with not only bovine and porcine TSH, FSH, and LH but also the alpha-subunit of these 3 hormones. However, no reaction with the beta-subunit of these 3 hormones was observed. These results indicate that these TSH antibodies are found mainly in epitope in the alpha-subunit of bovine pituitary glycoprotein hormones (TSH, FSH, LH).

Animals↗

PubMed1993

Deregulated c-fos modulates B cell responses to switch mediators.

We examined effects of deregulated c-fos on the proliferation and differentiation of B cells in vitro, using splenic B cells from H2-c-fos transgenic mice. When these cells were cultured with lipopolysaccharide (LPS) plus recombinant interleukin 4 (rIL-4) (10(4) U/ml), the proliferative response of the B cells was augmented with any dose of LPS used. This augmented proliferation resulted in an increase in IgG1 production in the culture, at the lower concentrations of LPS (< 2.5 micrograms/ml). However, H2-c-fos B cells did not produce IgG1 in the culture at higher concentrations of LPS (> 5 micrograms/ml) probably due to the perturbation of B cell differentiation to antibody-forming cells. These results suggest that the deregulated expression of c-fos modulates the proliferation and differentiation of B cells stimulated with LPS plus rIL-4.

Animals↗

PubMed1993

Pharmacological profile of AD-5423, a novel antipsychotic with both potent dopamine-D2 and serotonin-S2 antagonist properties.

The pharmacological properties of AD-5423 [2-(4-ethyl-1-piper-azinyl)-4- (4-fluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine] were studied in biochemical and behavioral tests. In vitro, AD-5423 bound preferentially to dopamine (DA)-D2 (Ki, 14.8 nM; cf. haloperidol, 8.79 nM; and clozapine, 149 nM) and serotonin (5-HT)-S2 (Ki, 3.98 nM; cf. haloperidol, 26.8 nM; and clozapine, 8.66 nM) receptors. It displayed low affinity for adrenaline (Ad)-alpha-1 (Ki, 56.3 nM) receptors and was virtually devoid of binding to DA-D1 (Ki, 2870 nM), 5-HT-S3, Ad-alpha-2, Ad-beta, muscarine, tau-aminobutyric acid and benzodiazepine receptors. In addition, AD-5423 was only a weak inhibitor of DA, 5-HT and noradrenaline uptake systems. When administered p.o., AD-5423 (0.3-10 mg/kg) increased brain contents of the DA metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid in mice and rats and the 5-HT metabolite 5-hydroxyindoleacetic acid in mice. Behaviorally, AD-5423 (0.2-2 mg/kg p.o.) decreased exploratory activity in mice, suppressed conditioned avoidance responding and methamphetamine-induced hyperactivity in mice and rats, antagonized apomorphine-induced gnawing in rats and vomiting in dogs and reduced hostile responses in monkeys. In these effects, AD-5423 was more or less equi-potent to haloperidol. However, AD-5423 (10 mg/kg p.o.), unlike haloperidol, did not antagonize SKF38393-induced vacuous oral movements in rats. Head twitches induced by 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane in mice and by para-chloroamphetamine in rats were antagonized by AD-5423 at much lower doses (0.5-2 mg/kg p.o.) than those of haloperidol and clozapine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Increased serum concentration of type IV collagen peptide and type III collagen peptide in hyperthyroidism.

Serum concentration of type IV collagen peptide, the 7S domain of type IV collagen (type IV collagen 7S) and the amino terminal propeptide of type III procollagen (type III procollagen peptide) is thought to be a useful marker of progressive liver disease. In the present study, serum levels of these collagens in patients with thyroidal diseases with normal liver function were assayed. Increased levels in the hyperthyroid state and relatively decreased levels in the hypothyroid state were observed. The increased levels in hyperthyroidism was most prominent in type IV collagen peptide. The increased level became normal in the subsidence of hyperthyroidism by treatment with anti-thyroid drug. A positive correlation between serum type IV collagen peptide levels and serum thyroid hormone levels such as T4, T3, free T4 and free T3 was observed. These facts show that serum type IV collagen peptide may be influenced by not only liver disease but also serum thyroid hormone levels. Type IV collagen peptide may provide a useful biochemical marker of hyperthyroid state.

Collagen↗

PubMed1992

Immunohistochemical analysis of spinal intradural xanthomatosis developed in a patient with phytosterolemia.

Multiple intradural xanthomatous tumors developed in 48-year-old female with familial phytosterolemia. These tumors were restricted to the spinal denticulate ligaments. Histological and immunohistochemical findings were fundamentally similar to those of tendinous xanthomas. The major cellular component of these tumors were identified as of mono-histiocytic origin because they possessed myeloid histiocytic antigen (Mac 387), CD11c and lysozyme but not CD15. Sitosterols, campesterols and cholestanols were recovered from the extract of the tumors and the lesions were confirmed to be phytosterolemic xanthomas. Schwann cells stained with anti-S100 protein were confined to the perivascular small nerve bundles and did not show xanthomatous change. Although immunohistochemical preparation of epithelial membrane antigen and desmoplakin I+II revealed the presence of non-neoplastic meningothelial cells in the superficial portion of the tumors, they were too few to play a significant role in the development of these xanthomas.

Chromatography, Liquid↗

PubMed1992

Deregulated c-fos augments the expression of IL-2 gene in T cells stimulated with anti-CD3 antibody.

The expression of IL-2 gene in T cells stimulated with immobilized anti-CD3 antibody is controlled by several transcription factors like as AP-1, IL-2 kappa B and NFAT. We studied an effect of deregulated c-fos, a component of AP-1, in the expression of IL-2 gene in T cells by using splenic T cells from transgenic mice carrying the exogenous c-fos gene under the control of the H2-Kb promoter (H2-c-fos). The IL-2 production of H2-c-fos T cells stimulated with anti-CD3 antibody was enhanced and prolonged. Levels of AP-1 and IL-2 kappa B transcription factors in the nuclear extract from the H2-c-fos T cells were also augmented. These results suggest that c-Fos is one of the major regulatory factors for the expression of IL-2 gene in T cells activated with anti-CD3 antibody.

Animals↗

PubMed1992

[Renal and neurologic symptoms due to cryoglobulinemia complicated with rheumatoid arthritis and Sjögren's syndrome].

A 55-year-old woman with rheumatoid arthritis and Sjögren's syndrome developed complications of acute renal failure and symmetrical polyneuropathy. Laboratory examination revealed macroglobulinemia, positive cryoglobulin, and low complement levels. Kidney biopsy specimen revealed "thrombi" in glomerular capillary loops that were positive for PAS stain and negative for Congo red stain. Sural nerve biopsy specimens showed axonal degeneration and subsequent myelin loss due to vasculitis. We, therefore, diagnosed renal failure and polyneuropathy due to cryoglobulinemia, and treated the patient with double filtration plasmapheresis. Moreover, lymph node biopsy specimen revealed malignant lymphoma of the follicular, small-cell lymphoplasmocytic type which seemed to be related to the macroglobulinemia. The complication of cryoglobulinemia must be taken into consideration in patients with autoimmune disease or lymphoproliferative disorder complicated with renal or neurologic symptoms.

Acute Kidney Injury↗

PubMed1991

Anti-bovine thyrotropin autoantibodies in patients with Hashimoto's thyroiditis, subacute thyroiditis, and systemic lupus erythematosus.

We report four cases found to have anti-bovine thyrotropin (bTSH) antibodies, two with Hashimoto's thyroiditis and the other two, each with subacute thyroiditis and systemic lupus erythematosus (SLE). The unusually high negative titers of anti-TSH receptor antibodies (Case no. 1, -43.1%; Case no. 2, -34.9%; Case no. 3, -55.2%; Case no. 4, -59.9%) led to the incidental finding of the presence of anti-bovine (bTSH) antibodies in each patient. Case no. 1 was diagnosed to have Hashimoto's thyroiditis and was treated with L-thyroxine (L-T4). With the treatment, serum free T4 (FT4)normalized with a decline in the serum TSH concentration. The other patient diagnosed to have Hashimoto's thyroiditis (Case no. 2) remained euthyroid even without supplemental thyroid hormone therapy and the serum concentrations of FT4 and TSH stayed within the normal range. The third is a case of subacute thyroiditis (Case no. 3) with a typical clinical course of the disease. She had the anti-bTSH antibodies on her first outpatient visit. Serial examination of her sera disclosed the antibody titers to be on the same range over the 28 months after the onset of the symptoms. The fourth is a patient with SLE who had been treated with steroid (alternative day therapy of 40 mg/day prednisolone). Titers of the anti-bTSH antibodies spontaneously declined to the negative level 5 months later. None of the four cases had antibodies against human TSH alpha-subunit of bovine LH and alpha-subunit of bovine FSH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗