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Biomedical subjects

K Tahara

Publications and source records attributed to K Tahara.

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

Diagnostic evaluation of diabetic retinopathy by 30-Hz flicker electroretinography.

The peak latency in 30-Hz flicker electroretinography (ERG) was determined in patients with diabetic retinopathy, using a newly developed contact lens electrode with built-in light-emitting diode. A good correlation was obtained between the peak latency of flicker ERG and that of oscillatory potentials of flash ERG. The peak latency of the flicker ERG was only slightly prolonged in background retinopathy, but markedly prolonged in proliferative retinopathy. The stage of pre-proliferative retinopathy with normal peak latency in flicker ERG may be a compensatory state of the retina, which is the most appropriate stage for laser treatment of diabetic retinopathy.

Adult↗
PubMed1992

Molecular basis for the autoreactivity against thyroid stimulating hormone receptor.

The present report identifies an important immunogenic region of the TSH receptor and determinants on the TSH receptor for the two types of autoantibodies seen in hyperthyroid Graves' disease and hypothyroid idiopathic myxedema, TSAbs and TSBAbs, respectively. The immunogenic domain with no important functional determinants, is contained within residues 303-382 and involves residues 352-366 in particular. There are determinants flanking the immunogenic domain on the C-terminal portion of the receptor which are the TSBAb and high affinity TSH binding sites: residues 295-306, 387-395, and tyrosine 385. Determinants on the N-terminal portion of the external domain, centered on residues 38-45, are TSAb interactions linked to low affinity TSH binding important for signal generation: threonine 40 and residues 30-33, 34-37, 42-45, 52-56, and 58-61. These determinants are conserved in human and rat receptors, are not present in gonadotropin receptors, and are each related to separate actions of TSH: binding vs. signal generation. They can, therefore, account for organ specific autoimmunity and the different disease expression effected by TSBAbs vs TSAbs, i.e. hypo- vs. hyperthyroidism, respectively. It is proposed that, in the thyroid, hormonal (TSH, insulin, hydrocortisone, IGF-I) suppression of class I genes might be one means of preserving self-tolerance in the face of the hormone action to increase the expression of tissue specific genes such as thyroglobulin and thyroid peroxidase. Inappropriately high class I expression in the thyroid, i.e. if induced by interferon, viruses, or some as yet unknown agent, would contribute to the generation of autoimmune disease. Thus, it would result in increased antigen presentation to the immune system, particularly those autoantigens increased by TSH and its cAMP signal such as thyroglobulin or thyroid peroxidase, or whose turnover is increased by TSH and its cAMP signal, such as the TSH receptor. In the case of the latter, peptide 352-366, known to be near a protease sensitive site on the receptor [41,49], would now act as a potent self-antigen and induce the formation of receptor autoantibodies. It is further proposed that methimazole and high doses of iodide are therapeutically effective agents in thyroid autoimmune disease because they, in part, decrease MHC class I gene expression. Speculation is presented which suggests that elimination of negative regulation of MHC class I and the TSH receptor is an important factor in the development of autoimmune thyroid disease.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1991

Immunoglobulins from Graves' disease patients interact with different sites on TSH receptor/LH-CG receptor chimeras than either TSH or immunoglobulins from idiopathic myxedema patients.

To examine the identity of binding sites for thyrotropin (TSH) and thyroid stimulating antibodies (TSAbs) associated with Graves' disease, we constructed eight human TSH receptor/rat LH-CG receptor chimeras. Substitution of amino acid residues 8-165 of the TSH receptor with the corresponding LH-CG receptor segment (Mc1 + 2) results in a chimera which retains high affinity TSH binding and the cAMP response to TSH but loses both the cAMP response to Graves' IgG and Graves' IgG inhibition of TSH binding. Two of three IgGs from idiopathic myxedema patients which contain thyroid stimulation blocking antibodies (TSBAbs) still, however, react with this chimera. Chimeras which substitute residues 90-165 (Mc2) and 261-370 (Mc4) retain the ability to interact with TSH, Graves' IgG, and idiopathic myxedema IgG. The data thus suggest that residues 8-165 contain an epitope specific for TSAbs and that TSH receptor determinants important for the activities of TSAbs and TSH are not identical. Further, binding sites for TSBAbs in idiopathic myxedema may be different from receptor binding sites for both Graves' IgG TSAb as well as TSH and may be different in individual patients.

Base Sequence↗
PubMed1991

Regulation of prostaglandin synthesis by thyrotropin, insulin or insulin-like growth factor-I, and serum in FRTL-5 rat thyroid cells.

The present report shows that thyrotropin (TSH) regulates all three steps involved in prostaglandin synthesis in FRTL-5 rat thyroid cells, i.e. arachidonic acid release from membrane phospholipids, cyclooxygenase (prostaglandin H synthase) action, and individual prostaglandin formation; however, its action at specific steps may require the presence of, or can be duplicated by, insulin, insulin-like growth factor-I (IGF-I), and/or a serum factor. Thus, TSH releases free arachidonic acid from rat FRTL-5 thyroid cells whose phospholipid fraction is radiolabeled with [3H]arachidonic acid; this action involves a pertussis toxin-sensitive G protein, is not cAMP mediated, and does not require insulin or 5% serum. To quantitate TSH effects on cyclooxygenase activity and on individual prostaglandin formation, a homogenate system and a rapid reversed-phase high pressure liquid chromatography procedure have been developed to measure cyclooxygenase metabolites. TSH increased cyclooxygenase activity in homogenates only if the cells were also exposed to insulin, IGF-I, and/or 5% calf serum; TSH alone had no apparent effect on the activity. Maximal activation, 4-fold over basal/micrograms of DNA, took 36 h to achieve and reflected, at least in part, an increase in cyclooxygenase gene expression. Like cyclooxygenase activity, induction of prostaglandin E2 production required 2 or more factors, i.e. TSH plus insulin/IGF-I or TSH plus insulin/IGF-I plus serum. Increased production of prostaglandin D2, could, however, be detected if cells were treated with TSH alone and the TSH activity could be duplicated by insulin, IGF-I, or calf serum alone.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1991

The TSH receptor in autoimmune Basedow's disease.

The cloning approaches of the past two years have opened new doors to the pursuit of our understanding Basedow's disease. The cloning of the TSH receptor is the most dramatic step; nevertheless, all the proteins mentioned in the following appear to be important molecules in the bioactivity of the thyroid cell and are implicated as autoantigens.

Amino Acid Sequence↗
PubMed1991

Hepatic uptake of lipid-soluble drugs from fat emulsion.

Oil violet in a fat emulsion was taken up into the parenchymal cells of rat liver in vitro. The uptake was greater at 37 degrees C than 25 degrees C or 4 degrees C, and it was increased by addition of postheparin plasma including lipoprotein lipase activity into the reaction medium. The uptake from the emulsion with smaller particles was greater than that from the emulsion with larger particles. The hepatic uptake of 14C-cholesteryl oleate in the emulsion by recirculating perfusion of the liver in situ was also increased by postheparin plasma in the perfusion medium. Its enhancing effect was found for distribution in the parenchymal cells but not in the Kupffer cells. The previous perfusion of Intralipos of the commercial fat emulsion reduced the hepatic uptake of 14C-cholesteryl oleate in the emulsion. The emulsion particle sizes were reduced by postheparin plasma both in vitro and in situ. Consequently, it was suggested that a lipid-soluble compound entrapped in the fat emulsion is taken up into the parenchymal cells by receptor-mediated process via the reduced particle sizes emulsion (remnant), which is a mechanism similar to the dietary fat metabolism.

Animals↗
PubMed1990

Repeatedly passed FRTL-5 rat thyroid cells can develop insulin and insulin-like growth factor-I-sensitive cyclooxygenase and prostaglandin E2 isomerase-like activities together with altered basal and thyrotropin-responsive thymidine incorporation into DNA.

Repeatedly passed or aged rat FRTL-5 thyroid cells develop a high level of basal [3H]thymidine incorporation into DNA and a reduced response to TSH in medium containing 5% serum and insulin (5H medium). The basal [3H]thymidine incorporation into DNA of aged cells can exceed the TSH-induced increase in earlier passages of the same cell line (fresh cells) and the TSH response decreases from more than 10-fold above basal in fresh cells to less than 2-fold in aged cells. This change is not associated with a loss of the diploid karyotype, a change in basal cAMP levels, or a change in dependence on TSH for cell growth. Attenuation of the TSH response in the [3H]thymidine incorporation assay is more evident than the reduced effect of TSH on cAMP levels or iodide transport; moreover, the TSH effect on cAMP levels does not correlate with that on [3H] thymidine incorporation as a function of hormone concentration. The high basal activity in [3H]thymidine incorporation into DNA in aged cells is due to an increased responsiveness to insulin, insulin-like growth factor-I (IGF-I), or serum. Thus, removal of serum and insulin from the medium eliminates the high basal [3H]thymidine incorporation into DNA, and this activity is restored by insulin or IGF-I in a concentration-dependent manner. The increased responsiveness of aged cells to insulin or IGF-I is inhibited by indomethacin or hydrocortisone and is associated with insulin or IGF-I, but not TSH, stimulation of cyclooxygenase and prostaglandin E2 (PGE2) isomerase-like activity. Fresh cells, in contrast, require TSH plus insulin or IGF-I to increase these activities. Increased responsiveness of cyclooxygenase activity to insulin or IGF-I in aged cells reflects at least in part an increase in cyclooxygenase mRNA levels. We suggest that insulin/IGF-I stimulation of PGE2 production leads to the high basal thymidine incorporation into DNA in aged cells maintained in TSH-depleted (5H) medium; the reduced stimulation by TSH of cAMP content or iodide uptake may reflect PG inhibition (negative feedback regulation) of cAMP production.

Animals↗
PubMed1989

The arachidonic acid signal system in the thyroid: regulation by thyrotropin and insulin/IGF-I.

The present study and the previous report (6) show that the cyclooxygenase path is a primary route of metabolism of arachidonic acid in FRTL-5 rat thyroid cells. The production of PGD2 and PGE2 is an active process in intact cells treated with complete medium including TSH, insulin and 5% calf serum. In contrast, PGF2 alpha and HHT are probably nonenzymatic degradation products of an unstable intermediate, PGH2, since the two compounds are produced and occupy a significant proportion of the cyclooxygenase metabolites only in the homogenate system; this is true in other cells. Although the production of prostaglandins involves three steps, i.e. the release of free arachidonic acid, the production of PGH2 by PGH synthase (cyclooxygenase) and the conversion of PGH2 to various prostaglandins by specific isomerases or synthetases, the first step, the release of free arachidonic acid, has been, until recently, believed to be the sole step important for the regulation of prostaglandin synthesis. This presumption rested on the following observations. Only the free form of arachidonic acid is converted to prostaglandins and the intracellular free arachidonic acid pool is very small compared to the esterified form in phospholipids. The size of the free arachidonic acid pool is regulated by the balance between release from phospholipids by phospholipases and reacylation into phospholipids. When resting cells are stimulated, the release of arachidonic acid and the production of prostaglandins increase concomitantly. The present study shows, however, that all three steps of prostaglandin synthesis are under regulatory control in FRTL-5 rat thyroid cells and that the control is a complex process involving TSH, insulin/IGF-I, and serum. The first step is primarily under the control of TSH. TSH increases the synthesis of arachidonic acid and also, like norepinephrine (5, 6) induces the release of arachidonic acid from the cell by a mechanism involving a pertussis toxin-sensitive G protein. Regulation of the second step can be estimated by measuring cyclooxygenase activity. The present report shows that TSH increases cyclooxygenase activity, presumably by increasing gene expression, but that the TSH effect on cyclooxygenase activity requires insulin/IGF-I or serum. This result is similar to studies showing the effect of TSH and insulin/IGF-I on glycosaminoglycan synthesis, thyroglobulin synthesis, and growth in FRTL-5 thyroid cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Effect of serum on dose- and temperature-dependent hepatic uptake of multilamellar vesicles (MLV).

Effects of the addition of serum to the perfusate on hepatic uptake of multilamellar vesicles (MLV) were examined in recirculating perfused rat liver. MLV was labelled with both membrane lipid marker ([14C]cholesteryl oleate) and aqueous phase marker ([3H]inulin or 5(6)-carboxyfluorescein (CF)). The uptake rates of [14C]cholesteryl oleate and CF at 37 degrees C coincided well, indicating both markers to be taken up as MLV. Inulin was released from MLV at 37 degrees C but its uptake rate tended to approach that of [14C]cholesteryl oleate at 4 degrees C or at high MLV dose. Some factor in serum promoted MLV uptake at 37 degrees C, but its effect was inhibited at 4 degrees C. The promoting effect was indicated to be possibly due to activation of adsorption of MLV to the hepatic Kupffer cell surface and/or that of phagocytosis by the cells. The saturation of MLV uptake was observed with increase in MLV dose, suggesting the saturation of MLV adsorption to the hepatic cell or the consumption of serum factor which promotes MLV uptake.

Animals↗
PubMed1988

Effects of the high K+/Na+ deficient solution on mechanical response and wet weight of tissue in vas deferens and seminal vesicle in guinea-pig.

In the present experiments, we investigated contractions of guinea-pig vas deferens or seminal vesicle in various kinds of high K+ solution. The vas deferens showed a phasic contraction followed by a tonic one in hyperosmotic 65 mM KCl (hyper-65K+), isosmotic 60 mM or 120 mM KCl solution. However, isosmotic 154 mM KCl (iso-154K+) solution induced a large phasic contraction followed by a gradual relaxation. Applications of the high K+ solutions to the preparation of seminal vesicle showed almost similar results in tension to those of the vas deferens. In the vas deferens or seminal vesicle, an application of hyper-65K+ solution significantly decreased the relative value for the wet weight of the tissue at 120 min, but that of iso-154K+ solution did not affect the wet weight of both the muscles. In the vas deferens, an hyperosmotic addition of sucrose at a concentration of 25 to 100 mM slightly prevented the tension decreased by the iso-154K+ solution and slightly decreased the relative wet weight. In the seminal vesicle, increasing sucrose concentration significantly increased the tension, but decreased the relative wet weight. In both the muscles of vas deferens and seminal vesicle, an addition of pyrvate or oxalacetate (5.5 mM) to the iso-154K+ solution without glucose maintained the muscle tension at a maximal level in the iso-154K+ solution with glucose for 120 min. Further, the tension decrease in both the muscles induced by iso-154K+ solution was also prevented by hyperosmotic application of NaCl. From these results, it is suggested that the tension decrease by high K+, Na+-deficient solution in the vas deferens is mainly caused by an inhibition of glucose utilization by Na+-deficiency in the medium, however, the seminal vesicle is probably due to the cell swelling and partly the inhibition of glucose utilization by it.

Animals↗
PubMed1987

[A case of primary extramedullary plasmacytoma in the posterior cervical portion].

This case involves a 16-year-old woman with a posterior cervical tumor. Histologically, it was found to be a extramedullary plasmacytoma (EMP). Immunohistochemically, IgG was present in the plasma cells that were shown to be atypia by the PAP method. Laboratory data revealed no other abnormalities. A surgical excision of the tumor was performed with a dissection of the relevant lymph nodes. Although irradiation and chemotherapy were administered postoperatively, multiple bone metastasis was found a month after the operation, and the patient died 8 months later.

Adolescent↗
PubMed1986

Clinical and epidemiological studies of eicosapentaenoic acid (EPA) in Japan.

From 1950 to 1980, the gross alteration in dietary habit in Japan was noted. Intake of total calories has markedly increased. This could be most likely due to a remarkable increase in intake of fat, especially animal fat, egg and milk products. A marked decrease of mortality rate due to cerebral hemorrhage and in contrast a marked increase of mortality rate due to cerebral infarction and ischemic heart disease were noted. An epidemiological study of the intake of fish meat (EPA intake) and the mortality rate of adult diseases was performed in a fishing area and in a farming area in Chiba Prefecture. Intake of fish meat (EPA) by the residents of the fishing area was 2-3 times higher than by the residents of the farming area. The mortality rate due to ischemic heart disease and cerebral vascular diseases tended to be lower in the fishing area than in the farming area. EPA manufactured from sardine oil was orally given to normal subjects and to patients with cerebro- and cardiovascular diseases for 4-16 weeks. Significantly decreased platelet aggregation, decreased platelet retention, lowered whole blood viscosity, prolonged bleeding time, increased erythrocyte deformability, improvement of hyperlipidemia, and clinical improvement in some patients were noted. 12-Lipoxygenase metabolites of EPA (12-HPEPE) and arachidonic acid (12-HPETE) have an equipotent inhibitory action on platelet function.

Arachidonate 12-Lipoxygenase↗