Biomedical subjects

T Ban

Publications and source records attributed to T Ban.

At least 91 records · Page 5Linked to original sources

PubMed1993

Prognostic value of an increase in fluorine-18 deoxyglucose uptake in patients with myocardial infarction: comparison with stress thallium imaging.

OBJECTIVES: This study was undertaken to evaluate the prognostic value of an increase in fluorine (F)-18 deoxyglucose uptake compared with clinical, angiographic and stress thallium findings in patients with myocardial infarction. BACKGROUND: Positron emission tomography (PET) imaging using F-18 deoxyglucose has been applied to assess tissue viability in patients with coronary artery disease. We hypothesized that patients with a myocardial segment with augmented F-18 deoxyglucose uptake are at high risk for a future cardiac event. METHODS: One hundred fifty-eight consecutive patients with myocardial infarction referred for F-18 deoxyglucose PET and stress thallium scans were studied. Follow-up was obtained in 84 patients at a mean interval of 23 months to investigate prognostic implications of radionuclide studies. RESULTS: Seventeen patients had a cardiac event during the follow-up interval. Univariate analysis showed that an increase in F-18 deoxyglucose uptake was the best predictor of a future cardiac event (p = 0.0006), followed by the number of stenosed vessels (p = 0.008). In the multivariate analysis, when an increase in F-18 deoxyglucose uptake was entered into the model, only angiographic variables had an independent prognostic value, whereas no other radionuclide variables showed significant prognostic value. Among patients who did not show redistribution, a future cardiac event was observed more often in patients with than in those without an increase in F-18 deoxyglucose uptake (p < 0.05). CONCLUSIONS: Thus, an increase in F-18 deoxyglucose uptake seemed to be the best predictor of a future cardiac event among all clinical, angiographic and radionuclide variables in this study of stable patients with myocardial infarction. Even when a stress thallium-201 scan does not show redistribution, those patients who have an increase in F-18 deoxyglucose uptake in a PET study may be at risk for a future cardiac event, and these patients may need aggressive treatment to prevent a future cardiac event.

Aged↗

PubMed1993

[Development and medical application of Er-YAG laser].

Result of developments of Er-YAG laser and its delivery system were reported. Er-YAG laser's wavelength is 2.94 microns, the beam absorption rate by water is higher than other laser beam. Er-YAG laser has repeated pulse oscillation, pulse width is 400 mu, sec, the repeat frequency is between 5 to 10 pulse per second. The mean power is 4 W maximum, 10 pps. The fibers of laser are made of zirconium-F-glass. We carried out a study on the possible application of the Er-YAG laser on the rabbit arteries and myocardium and human arteries were examined in vitro. Very clear cuts were observed on the histological examination. There were no evidence of thermal damage, no carbonization on the sharp cutting surface. Experimental result showed that Er-YAG lasers had good potential for angioplastic laser.

Angioplasty, Laser↗

PubMed1993

Relationship between resting cytosolic Ca2+ and responses induced by N-methyl-D-aspartate in hippocampal neurons.

Cytosolic calcium concentrations ([Ca2+]i) in cultured hippocampal neurons from rat embryos were measured using fura-2. Neurons with higher resting [Ca2+]i showed greater [Ca2+]i responses to N-methyl-D-aspartate (NMDA) and K+ depolarization. There was a strong relationship between resting [Ca2+]i and the maximal changes in [Ca2+]i (delta[Ca2+]i), which fit the our proposed equation to describe this relationship.

Animals↗

PubMed1993

Decreased expression of DCC mRNA in human colorectal cancers.

The mRNA expression levels of DCC gene, which is cloned from the deleted region of chromosome 18q in colorectal cancers and thought to be a tumor-suppressor gene, was evaluated in tissue specimens surgically resected from patients with colorectal cancer by RT-PCR. This method was chosen as the expression level of DCC mRNA is below the detectable level for Northern-blot analysis. Semi-quantitative measurements of DCC mRNA were performed based on a standard curve defined by serial dilution of DCC cDNA. As a result, the expression level of DCC mRNA was found to be lower in 17 out of 30 colorectal cancers than in adjacent non-cancerous tissues. Inclusion of smooth muscle in tissue specimens was observed to have little disturbing effect on comparisons between cancerous and non-cancerous regions. In addition, all 4 specimens of colorectal cancer with liver metastasis showed the decreased expression level of DCC mRNA, suggesting that functional loss of DCC in cancerous tissues may play an important role in metastatic events.

Actins↗

PubMed1993

Use of thyrotropin receptor (TSHR) mutants to detect stimulating TSHR antibodies in hypothyroid patients with idiopathic myxedema, who have blocking TSHR antibodies.

Deletions of residues 295-306, 299-301, and 387-395 of the TSH receptor, as well as point mutations of cysteine 301 or 390 to serine, and tyrosine 385 to phenylalanine or alanine, markedly diminish the ability of a transfected receptor to measure the activity of blocking TSH receptor autoantibodies (TSHRAbs) in patients with idiopathic myxedema and hypothyroidism, but not stimulating TSHRAbs in Graves' patients. This has allowed us to use these mutants to detect stimulating TSHRAb activity in the sera of hypothyroid patients with idiopathic myxedema who have blocking TSHRAbs. In 7 such patients, we show that 50% or more have significant stimulatory activity in cells transfected with mutant receptors, as evidenced by the ability of the immunoglobulin G to directly increase cAMP levels or to enhance the ability of TSH or a Graves' stimulating TSHRAb to increase cAMP levels. Three of the TSH receptor mutants, deletions of residues 295-306 and 387-395 and the point mutation of cysteine 301 to serine, are shown to be particularly useful in these assays and may be useful to clarify the pathogenetic role and clinical significance of stimulating TSHRAbs in patients with autoimmune thyroid disease who also have blocking TSHRAbs.

Animals↗

PubMed1993

Receptor cross-talk can optimize assays for autoantibodies to the thyrotropin receptor: effect of phenylisopropyladenosine on adenosine 3',5'-monophosphate and inositol phosphate levels in rat FRTL-5 thyroid cells.

Immunoglobulins (IgG) from patients with Graves' disease increase inositol phosphate (IP) as well as cAMP production in rat thyroid FRTL-5 cells; IgGs from normal control subjects do not. Graves' IgG-and TSH-induced IP formation is inhibited by blocking TSH receptor (TSHR) antibodies from hypothyroid patients with primary myxedema, as is the cAMP response; this suggests that the Graves' IgG are acting through the TSHR to induce both the cAMP and phosphatidyl-inositol 4,5-biphosphate signal cascades in FRTL-5 thyroid cells as in cells with recombinant TSHR. Optimal conditions for measuring the Graves' IgG-induced IP increase include a NaCl-free Hanks' Balanced Salt Solution (HBSS) buffer system and a P1 purinergic receptor agonist; the action of each is additive. Optimization by NaCl-free HBSS is similar to that observed in cAMP assays and is specific for TSH or Graves' IgG; thus, NaCl-free HBSS did not affect ATP-induced, and actually inhibited norepinephrine-induced, IP production in FRTL-5 cells. The P1 purinergic receptor agonist acts via receptor cross-talk, which also allows further optimization of cAMP assays. Thus, adenosine deaminase improves Graves' IgG-induced cAMP production by removing adenosine from the medium. Although NaCl-free HBSS improved TSH- or Graves' IgG-induced IP and cAMP production in cells with recombinant TSHR; the modulatory action of phenylisopropyladenosine was lost.

Animals↗

PubMed1993

Identification of thyroid-stimulating antibody-specific interaction sites in the N-terminal region of the thyrotropin receptor.

Using mutants of the N-terminal region (residues 30-76) of the rat TSH receptor (TSHR), which substitute corresponding segments of rat gonadotropin receptors or hydrophilic (serine) and hydrophobic (alanine) amino acids as appropriate, we show that residues 30-33, 34-37, 42-45, 52-56, and 58-61, in addition to threonine-40, are determinants for the interaction of thyroid-stimulating autoantibodies (stimulating TSHRAbs) with the TSHR. The most important, residues 34-37, 42-45, and 52-56, whose mutants lose stimulating TSHRAb activity with at least 11 of 12 (> 90%) of the Graves' immunoglobulins G tested, are, like threonine-40, in regions of the TSHR that are nonhomologous with gonadotropin receptors. These data establish at least in part, therefore, the basis for the thyroid-specific effects of stimulating TSHRAbs. In no case do the same mutants lose their reactivity with TSH or blocking-type TSHR autoantibodies (blocking TSHRAbs) from hypothyroid patients with idiopathic myxedema. Since the latter have been shown to interact with high affinity TSH-binding sites on the C-terminal portion of the external domain of the TSHR, stimulating TSHRAbs and blocking TSHRAbs react with different receptor determinants, which can be presumed to have different roles in receptor function. This can explain the hyper- or hypothyroidism of different thyroid autoimmune diseases with receptor antibodies. Residues 30-33, 42-45, and threonine-40 appear to be related to the agonist action of TSH, since in each case mutation results in low affinity TSH binding, but normal TSH-increased cAMP activity, similar, for example, to a beta-adrenergic agonist. Using a receptor antibody to identify different receptor forms in the membrane, we can also identify determinants in this N-terminal region (residues 30-76) whose mutation results in a loss of all activities without apparently altering receptor synthesis, processing, or integration within the bilayer. These are residues 38 and 39, cysteine-41, residues 46-51, leucine-57, threonine-62, and, within residues 66-76, serine-69, alanine-71, phenylalanine-72, serine-74, leucine-75, and proline-76. We suggest that these residues are at the very least important in the conformational array of receptor determinants necessary for interactions with TSH and stimulating TSHRAbs.

Amino Acid Sequence↗

PubMed1993

Substitutions of different regions of the third cytoplasmic loop of the thyrotropin (TSH) receptor have selective effects on constitutive, TSH-, and TSH receptor autoantibody-stimulated phosphoinositide and 3',5'-cyclic adenosine monophosphate signal generation.

TSH and immunoglobulin G (IgG) preparations from patients with Graves' disease increase inositol phosphate as well as cAMP formation in Cos-7 cells transfected with rat TSH receptor (TSHR) cDNA. In a previous report, we mutated alanine 623 of the third cytoplasmic loop (residues 605-625) of the TSHR and showed it was critical for TSH and Graves' IgG initiation of phosphatidylinositol bisphosphate (PIP2) but not cAMP signaling. In this report, we substituted residues in the third loop of the TSHR with sequences from the N- and C-termini of the third loop of the alpha 1- and beta 2-adrenergic receptors (ARs), which computer analysis has identified as homologous to those in the TSHR. Alanine 623 is conserved in most ARs as well as in glycoprotein hormone receptors; there is, therefore, no change in alanine 623. After transfection of the mutant TSHR cDNAs into Cos-7 cells, we show that the mutant proteins are normally synthesized, processed, and incorporated into the membrane bilayer by Western blotting with a specific receptor antibody. We also show that the dissociation constant for TSH binding in all mutants is the same or lower than wild type TSHR. We then evaluated the ability of TSH or Graves' IgG to increase PIP2 and cAMP signals in each transfectant. Mutants A622 and B621 replace, respectively, residues 622-625 and 621-625 of the TSHR with alpha 1- and beta 2-AR residues from the C-terminus of the third cytoplasmic loop; mutants A607 and B605 replace, respectively, TSHR residues 607-609 and 605-609 with N-terminus residues from alpha 1- and beta 2-AR. All four mutants, like the alanine 623 mutant, result in transfected cells which lose TSH and Graves' IgG initiation of PIP2 but not cAMP signalling. Like the alanine 623 mutation to glutamic acid, the A607, B605, A622, and B621 mutants also result in decreased basal cAMP, but not inositol phosphate levels, relative to wild type receptor. In contrast to these results, mutants A610, B610, A617, and B617, which replace residues 610-613 or 617-620 of the TSHR with corresponding residues of the alpha 1- and beta 2-AR, retain TSH and Graves' IgG responsiveness in both inositol phosphate and cAMP assays. Mutation of residues 610-613, in fact, potentiates TSH-increased inositol phosphate production, despite having no effect on TSH-increased cAMP production.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1993

[Gating properties of cardiac Na channels: from the macroscopic Na current viewpoint].

The sodium channel plays essential roles in the initiation and propagation of action potentials (APs) in excitable tissues including the heart, nerves, and muscles. Na channels in these tissues undergo so-called activation and then inactivation upon step-depolarizations of the cell membrane. Hodgkin and Huxley, early in the 1950s, proposed a mathematical model to describe such events, which was based on voltage-clamp (V-C) data on axonal membranes. However, for the next 30 years or so since the pioneering work of the above workers, electrophysiological studies of the Na channel kinetics in the heart had relied exclusively on AP data (Vmax) as an indirect measure of the Na current instead of V-C data due to difficulty in determining V-C from the complex geometry of cardiac tissues. However, recent development of an isolation procedure for preparing single heart cells and the use of single patch-pipettes for high resolution V-C experiments on these cells have made direct recording of Na channel currents also possible in the heart. Voltage-clamp studies carried out for the last decade have provided several lines of evidence supporting the view that the Na channel properties in the heart of any animal species are somehow more complex than in the axonal membrane and hence showing that Hodgkin-Huxley model can not be directly applied to describe the Na channel behavior in the former type of tissues. Here, we review recent results from V-C studies on Na channel properties with special reference to the macroscopic Na current in cardiac tissues.

Animals↗

PubMed1993

Chimeric studies of the extracellular domain of the rat thyrotropin (TSH) receptor: amino acids (268-304) in the TSH receptor are involved in ligand high affinity binding, but not in TSH receptor-specific signal transduction.

A series of chimeric TSH-LH/CG receptors were constructed by substituting homologous segments of the extracellular domain of the rat TSH receptor with corresponding segments of rat LH/CG receptor: C1 (amino acids 37-123 substituted), C2 (91-112), C3 (173-234), C4 (233-266), C5 (268-304), C6 (112-305) and C7 (36-404). After transfection in Cos-7 cell, TSH- and LH/CG-receptor activities of these chimeras were evaluated and compared with those of deletion mutants involving the same residues [Kosugi et al. Thyroid 1:321 (1991)]. Western blot analyses revealed that most of the chimeric receptor proteins were normally synthesized and integrated in the membrane of transfected Cos-7 cells: an antibody to a TSH receptor specific synthetic peptide (residues 352-366) identified 170-190kDa and 90-100kDa TSH receptor structures in the plasma membrane fractions of Cos-7 cells transfected with wild-type TSH receptor cDNA and the C1 to C6 chimeras, but not C7 or wild LH/CG receptor cDNA. Despite this, no receptor except C5 exhibited any significant TSH receptor activities either in [12I]TSH binding or in cAMP responses to TSH and thyroid-stimulating antibodies (TSAbs) from Graves' patients. The chimeric receptor C5 exhibited only low affinity TSH binding (Kd = 3.5 x 10(-8) M), as did its counterpart the M2C mutant with residues 268-304 deleted. However, unlike M2C, C5 demonstrated a significant cAMP response to TSH as well as to TSAbs. The cAMP increase in response to TSH in the wild type receptor was observed at 10(-11) M TSH. In C5 the response was first evident at 10(-10) M TSH, but the maximum cAMP stimulation by TSH and TSAbs in C5 (EC50 = 6.7 x 10(-10) M) was approximately the same as the wild type receptor (EC50 = 1.5 x 10(-10) M). Inhibition of either TSH- or TSAb- stimulated cAMP increase by thyroid-stimulating blocking antibodies (TSBAbs) was also preserved in C5. These results suggest that amino acids 268-304 do not include an important determinant required for signal transduction, since a significant cAMP response to TSH and TSAbs was observed in the C5 receptor with these residues substituted. Additionally, these residues appear to be involved in ligand high affinity binding because high affinity TSH binding was lost in the chimeric receptor C5.

Amino Acid Sequence↗

PubMed1993

[Biosynthesis and secretion of vasopressin].

Oxytocin and vasopressin (AVP), which are octapeptides with a molecular mass of approximately 1.1 kd, are posterior pituitary hormones. AVP produced by magnocellular neurons in the supraoptic and paraventricular nuclei of the hypothalamus is in a form bound to the specific peptide neurophysin II, in the neurosecretory granula (NSG). Cleavage of this prohormone occurs within the NSGs during its transport via the axons to the neurohypophysis. Neurohypophyseal secretion of these peptides is believed to occur by exocytosis, which might be regulated by intracellular Ca++. The biosynthesis and secretion of AVP are mainly regulated by plasma osmolality (osmotic regulation) and blood pressure or blood volume (nonosmotic regulation). Some drugs, neurotransmitters, and other chemical agents modulate the regulation of AVP release.

Animals↗

PubMed1993

[Quantitative assessment of fibroblast viability in cryopreserved aortic valve allografts].

The purpose of this study is to clarify whether serum (fetal bovine serum or human serum) is necessary or not for cryopreservation of aortic valve allografts. The protective effects of fetal bovine serum compared with human serum were evaluated by means of quantitative assessment of fibroblast viability. Porcine aortic valves were excised and rinsed immediately after death, followed by treatment with low concentration antibiotics. Valves were gradually frozen at a control-rate of -1 degree C/min and then stored in liquid nitrogen vapor-phase. The samples were classified into three groups by nutrient medium as follows. Group A (n = 5); Dulbecco's Modified Eagle Medium (DMEM), Group B (n = 5); DMEM containing 10% fetal bovine serum, Group C (n = 5); DMEM containing 20% human serum. At 1 week, 1 month, and 3 months after initiation of storage, the valves were thawed rapidly and examined for fibroblast viability, which was assessed quantitatively by means of autoradiography with tritiated proline. After 1 week storage, the fibroblast viability rate reduced from 98% to 80.7% in group A, 79.4% in group B and 79.2% in group C respectively, but there were no significant differences among three groups. The viability rate decreased with the passage of time, and remained around 72% in all groups after 3 months storage. The histological examination did not show any changes in the structure of the valves in all samples up to 3 months of storage. The results demonstrate that the fibroblasts are still viable after 3 months storage by cryopreservation. The addition of fetal bovine serum or human serum does not improve fibroblast viability.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

[Quantitative assessment of improvement in perfusion after coronary bypass grafting: assessed by thallium-201 bull's eye subtraction polar map method].

To assess redistribution (RD) and improvement in regional perfusion after coronary bypass grafting (CABG) on thallium-201 SPECT images quantitatively, the Bull's eye subtraction polar (BS) map was created. BS map was created after subtraction of a normalized bull's eye polar map from another normalized polar map. The quantitative assessment on this map was compared to the visual qualitative analysis in 23 patients (115 segments) who received CABG. All of the improved segments after CABG showed > or = 15% on the BS map. On the other hand, 60% of the non improved segments showed < 10% on the BS map. Furthermore, 67% of the RD segments showing > or = 15% on the BS map before CABG improved in perfusion by > or = 15% on the BS map after CABG. On the BS map, an excellent correlation was observed between the extent of redistribution before CABG and the extent of improvement after CABG. Thus, BS map permits quantitative assessment of improvement in perfusion on T1 SPECT imaging, and this technique seems to be valuable for predicting improvement in perfusion after CABG.

Adult↗

PubMed1993

Skeletal muscle-powered ventricle. Effects of size and configuration on ventricular function.

The optimal size and configuration of skeletal muscle-powered ventricles are still undetermined. This study was aimed at comparing three types of skeletal muscle-powered ventricle: (A) a small size (15 ml capacity) double-layered pump, (B) a small size (15 ml capacity) single-layered pump, and (C) a large size (40 to 60 ml capacity) single-layered pump constructed sequentially with the same untrained latissimus dorsi muscle of 12 mongrel dogs. The skeletal muscle-powered ventricle was connected to a mock circulation system, the stroke volumes against 40 to 160 mm Hg of afterload at 5 to 60 mm Hg of preload were measured, and the stroke work was computer analyzed on line. Raising the preload from 5 to 60 mm Hg increased the peak isovolumic developed pressure (A) from 91.3 +/- 11.0 to 215.6 +/- 26.1 mm Hg, (B) from 92.8 +/- 12.0 to 166.3 +/- 19.0 mm Hg, and (C) from 32.3 +/- 5.2 to 121.4 +/- 15.5 mm Hg (p < 0.05, C versus A and B). Similarly, the stroke volume (stroke work) against an afterload of 120 mm Hg increased (A) from 3.8 +/- 0.5 ml (0.22 +/- 0.04 x 10(6) ergs) to 14.5 +/- 1.1 ml (1.05 +/- 0.11 x 10(6) ergs), (B) from 4.5 +/- 0.7 ml (0.30 +/- 0.08 x 10(6) ergs) to 10.7 +/- 0.9 ml (0.63 +/- 0.08 x 10(6) ergs), and (C) from 1.8 +/- 0.5 ml (0.09 +/- 0.04 x 10(6) ergs) to 24.0 +/- 3.6 ml (1.94 +/- 0.41 x 10(6) ergs) (p < 0.05, C versus B at 5 mm Hg of preload; p < 0.05, C versus A and B at preloads > or = 30 mm Hg). At low preloads (5 to 15 mm Hg) both small pumps generated a significantly larger stroke volume (stroke work) than the large pump, whereas at high preloads (> or = 30 mm Hg) the large pump generated a significantly larger stroke volume (stroke work) than the small pumps. It is concluded that under physiologic preload, B (small single-layered pump) performs better than or at least as well as A (small double-layered pump) and C (large single-layered pump), despite being constructed with only one half of the muscle mass used for either A or C.

Animals↗

PubMed1993

[A new skeletal muscle powered ventricle (SMPV) designed to work under physiologic preload].

To maximize pumping function the SMPV has been highly preloaded (over 30 mmHg); but the effects of pump size and configuration on the required preload have never been determined. A new double barrel dual chamber single layered (DCSL) SMPV having two SL small pumps in parallel was compared with a single chamber double layered small pump (SCDL). Stroke volume (SV) and stroke work (SW) were determined in acutely constructed SMPV using mongrel dog untrained latissimus dorsi: 10 DCSL and 12 SCDL. Under physiologic afterload (120 mmHg) and preload (15 mmHg), the DCSL displayed a significantly (p < 0.05) larger SV (9.9 +/- 1.2 ml) and SW (0.84 +/- 0.15 x 10(6) ergs) than the SCDL pumps (SV = 6.9 +/- 0.6 ml, and SW = 0.55 +/- 0.07 x 10(6) ergs). The DCSL pumps, requiring less muscle mass for its construction, indicated better performance under physiologic pre and afterload conditions than SCDL pumps.

Animals↗

PubMed1992

Role of cysteine residues in the extracellular domain and exoplasmic loops of the transmembrane domain of the TSH receptor: effect of mutation to serine on TSH receptor activity and response to thyroid stimulating autoantibodies.

The extracellular domain of the thyrotropin (TSH) receptor is the primary site with which TSH and receptor autoantibodies interact. Cysteines 494 or 569 in the 1st and 2nd exoplasmic loops, respectively, of the transmembrane domain of the TSH receptor are important in this process or in coupling ligand binding to signal generation. Thus, when either is mutated to serine, a receptor results which has no detectable TSH binding and no cAMP response to TSH or thyroid stimulating autoantibodies after transfection, despite the fact the mutant receptor is normally synthesized, processed, and integrated in the membrane, as evidenced by Western blotting using a TSH receptor-specific antibody. Additional site directed mutagenesis studies are performed in order to identify cysteine residues in the extracellular domain of the receptor which, with cysteines 494 and 569, are important for tertiary structure and receptor bioactivity.

Animals↗

PubMed1992

Mutation of alanine 623 in the third cytoplasmic loop of the rat thyrotropin (TSH) receptor results in a loss in the phosphoinositide but not cAMP signal induced by TSH and receptor autoantibodies.

Thyrotropin (TSH) and IgG preparations from patients with Graves' disease increase inositol phosphate as well as cAMP formation in Cos-7 cells transfected with rat TSH receptor cDNA. Mutation of alanine 623 in the carboxyl end of the third cytoplasmic loop of the TSH receptor, to lysine or glutamic acid, results in the loss of TSH- and Graves' IgG-stimulated inositol phosphate formation but not in stimulated cAMP formation. There is no effect of the mutations on basal or P2-purinergic receptor-mediated inositol phosphate formation. The mutations do not affect transfection efficiency or the synthesis, processing, or membrane integration of the receptor, as evidenced by the unchanged amount and composition of the TSH receptor forms on Western blots of membranes from transfected cells. The mutations increase the affinity of the TSH receptor for [125I]TSH and decrease Bmax; however, cells with an equivalently decreased Bmax as a result of transfection with lower levels of wild type receptor do not lose either TSH-induced inositol phosphate formation or cAMP signaling activity. Thus, in addition to discriminating between ligand-induced phosphatidylinositol bisphosphate and cAMP signals, the mutation appears to cause an altered receptor conformation which affects ligand binding to its large extracellular domain.

Alanine↗

PubMed1992

Hormonal regulation of major histocompatibility complex class I genes in rat thyroid FRTL-5 cells: thyroid-stimulating hormone induces a cAMP-mediated decrease in class I expression.

Thyrocytes normally express major histocompatibility complex (MHC) class I, but not class II, cell surface antigens. A rat thyrocyte cell line, FRTL-5, also expresses MHC class I antigens, in addition to a variety of thyroid-specific genes. Treatment of FRTL-5 thyrocytes with physiological concentrations of thyroid-stimulating hormone (TSH) has been shown to induce increased expressed of thyroglobulin and thyroid peroxidase but to simultaneously decrease expression of the TSH receptor. The reduction in TSH receptor expression by TSH is cAMP mediated. In the present study, it is demonstrated that, in thyrocytes treated with TSH, MHC class I expression decreases concomitant with the decrease in TSH receptor expression. This decreased expression is evidenced by reduced cell surface levels of MHC class I antigens, by reduced steady-state RNA levels, and by reduced transcription of the class I genes. TSH-mediated reduction of MHC class I gene transcription in FRTL-5 cells was mapped to a region within 135 base pairs of the promoter.

Animals↗