Biomedical subjects

T Ban

Publications and source records attributed to T Ban.

At least 19 recordsLinked to original sources

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↗

PubMed1992

Modelling of frequency-dependent effects of lignocaine homologues on the maximum upstroke velocity of action potentials in guinea-pig papillary muscles.

1. The effects of 14 lignocaine homologues on the maximum upstroke velocity (Vmax) of the action potentials (AP) were studied in guinea-pig papillary muscles. These drugs possess one, two or three methyl groups in different positions: an ortho-chloro, -carbomethoxy or -ethyl group instead of an ortho-methyl group; or an N-butyl group instead of an N-diethyl group in lignocaine molecules. 2. At 50-100 mumol/L, six drugs possessing two ortho substituents (but not the other eight) reduced Vmax more prominently at 2-4 Hz than at 1 Hz, and slowed the time courses of recovery of the premature responses. None of the drugs affected resting potential. 3. Besides the two-state piecewise exponential model (models I and II) frequently used, a time-dependent and time-independent, two-state model (model III) was formulated and applied to these experimental data. The above two groups were effectively distinguished by the difference of the estimated association and dissociation rate constants (model II) and equilibrium constants for phasic state (model III) and for resting (model II) or tonic (model III) states. 4. The equilibrium constants for resting or tonic state correlated well with log P (where P = the n-octanol: water partition coefficients), but correlated better with an indicator variable that denotes the existence of two ortho substituents, suggesting the importance of the contribution of steric factors to the activity.

Action Potentials↗

PubMed1992

Pleiotropic, multidrug-resistant phenotype and P-glycoprotein: a review.

This article is a brief review of recent knowledge about the pleiotropic resistant phenotype--multidrug-resistant (MDR) phenotype--which is responsible for cross-resistance in cancer chemotherapy. Thus it is possible to explain chemoresistance to vinca alkaloids, podophyllotoxins and anthracyclines. The MDR phenotype is associated with reduced intracellular drug accumulation by drug efflux, utilizing transmembrane P-glycoprotein (Gp170). The overexpression of Gp170 in normal and cancer tissues and the genetics are reported.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1992

Specific antibody to the thyrotropin receptor identifies multiple receptor forms in membranes of cells transfected with wild-type receptor complementary deoxyribonucleic acid: characterization of their relevance to receptor synthesis, processing, structure, and function.

An antibody to a peptide of the TSH receptor, residues 352-366 which are not present in gonadotropin receptors, specifically identifies three major forms of the receptor on Western blots of detergent-solubilized membrane preparations from Cos-7 cells transfected with full-length rat and human TSH receptor cDNA: 230, 180, and 95-100 kilodaltons (kDa), based on simultaneously run protein standards. The 95- to 100-kDa protein is absent in cells transfected with a mutant receptor with no signal peptide and is sensitive to endoglycosidase-F. Its size is consistent with the sum of amino acids predicted from its cDNA sequence (84 kDa after subtracting the signal peptide) plus its carbohydrate content (14 kDa estimated from glycosylation mutants). It alone is absent in two deletion mutants that have lost TSH binding and activity after transfection: M1 missing residues 37-121 and M2 missing residues 110-307. It, thus, appears to be the processed glycosylated functional receptor on the cell surface. The 230-kDa protein is a nonprocessed form of the receptor, as evidenced by its insensitivity to endoglycosidase-F and its continued presence in cells transfected with a mutant receptor with no signal peptide. It is the primary form identified in rat FRTL-5 thyroid cells that have a functioning TSH receptor; it is not present in rat FRT thyroid cells with no functioning TSH receptor or receptor RNA. It appears, therefore, to be a early synthetic form of the functional TSH receptor. The 180-kDa protein is endoglycosidase-F sensitive and appears to be a processed intermediate between the 230-kDa early synthetic form and the 95- to 100-kDa functional receptor, rather than a dimer of the latter. Thus, with decreases in size appropriate to a receptor monomer, it remains present in membranes from the M1 and M2 deletion mutants that contain the 230-kDa protein but are missing the 95- to 100-kDa receptor form in association with lost TSH binding and activity after transfection. Minor receptor forms (54 kDa in rat receptor transfectants, 54 and 48 kDa in human receptor transfectants) appear to be degraded forms of the processed and glycosylated 95- to 100-kDa receptor. The presence or absence of reducing agents in the detergent solubilization mixture does not change the pattern or amount of the receptor forms recognized by the antibody, including the 54-kDa form; however, boiling does.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

PubMed1992

Major histocompatibility complex class I gene expression in rat thyroid cells is regulated by hormones, methimazole, and iodide as well as interferon.

Autoimmune thyroid disease is associated with enhanced expression of major histocompatibility complex class I antigens on thyrocytes. To better understand this phenomenon, we have studied the normal expression of class I genes in FRTL-5 rat thyroid cells. A variety of hormones and growth factors that regulate the growth and function of these thyroid cells were found to decrease class I RNA levels: serum, insulin or insulin-like growth factor-I (IGF-I), and hydrocortisone. Antibody preparations from Graves' patients (thyroid-stimulating antibodies), which increase cAMP levels and stimulate the thyroid, also decrease class I RNA levels. This is consistent with the fact that TSH, via its cAMP signal, reduces class I transcripts. The class I response to TSH, serum, insulin, IGF-I, or hydrocortisone is specific, in that the same agents do not similarly affect TSH receptor, thyroglobulin, thyroid peroxidase, malic enzyme, or beta-actin RNA levels. Both gamma- and alpha-interferon increase class I RNA levels in FRTL-5 cells, even in the presence of the serum, IGF-I, or hormones noted above, i.e. they overcome hormonal negative regulation in normal thyrocytes. In contrast, methimazole treatment of rat FRTL-5 thyroid cells, but not rat fibroblasts or rat FRT thyroid cells, which have no TSH receptor and no TSH-regulated function, results in reduced class I RNA levels. The action of methimazole can inhibit interferon action, is transcriptional, is duplicated by iodide, and is additive with the negative regulatory action of hormones and serum factors, including TSH.

Animals↗

PubMed1992

Identification of separate determinants on the thyrotropin receptor reactive with Graves' thyroid-stimulating antibodies and with thyroid-stimulating blocking antibodies in idiopathic myxedema: these determinants have no homologous sequence on gonadotropin receptors.

Deletions, substitutions, or mutations of the rat TSH receptor extracellular domain between residues 20 and 107 (all residue numbers are determined by counting from the methionine start site) have been made by site-directed mutagenesis of receptor cDNA. After transfection in Cos-7 cells, constructs were evaluated for their ability to bind [125I]TSH or respond to TSH and thyroid-stimulating antibodies (TSAbs) from Graves' patients in assays measuring cAMP levels of the transfected cells. Assay results were compared to results from Cos-7 cells transfected with wild-type receptor constructs or vector alone. We identify threonine-40 as a TSAb-specific site whose mutation to asparagine, but not alanine, reduces TSAb activity 10-fold, but only minimally affects TSH-increased cAMP levels. We show that thyroid-stimulating blocking antibodies (TSBAbs), which block TSH or TSAb activity and are found in hypothyroid patients with idiopathic myxedema, continue to inhibit TSH-stimulated cAMP levels when threonine-40 is mutated to asparagine or alanine, suggesting that TSBAbs interact with different TSH receptor epitopes than the TSAb autoantibodies in Graves' patients. This is confirmed by the demonstration that these TSBAbs interact with high affinity TSH-binding sites previously identified at tyrosine-385 or at residues 295-306 of the extracellular domain of the TSH receptor. This is evidenced by a loss in the ability of TSBAbs to inhibit TSAb activity when these residues are mutated or deleted, respectively. Since the TSAb and TSBAb epitopes are in regions of the extracellular domain of the TSH receptor that have no homology in gonadotropin receptors, these data explain at least in part the organ-specific nature of TSH receptor autoantibodies in autoimmune thyroid disease. Data are additionally provided which indicate that residues 30-37 and 42-45, which flank the TSAb epitope at threonine-40, appear to be ligand interaction sites more important for high affinity TSH binding than for the ability of TSH to increase cAMP levels and that cysteine-41 is critical for TSH receptor conformation and expression on the surface of the cell. Thus, despite unchanged maximal values for TSH-increased cAMP levels, substitution of residues 42-45 or deletion of residues 30-37 results in receptors, which, by comparison to wild-type constructs, exhibit significantly worsened Kd values for TSH binding than EC50 values for TSH- or TSAb-increased cAMP activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Alanine↗

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↗

PubMed1992

[Ischemic myocardial injury evaluated using positron emission tomography in children with coronary artery disease: comparison with thallium-201 SPECT].

Regional myocardial perfusion and glucose metabolism were evaluated by positron emission tomography (PET) in children with coronary artery disease. Also, PET findings were compared with those of thallium-201 myocardial single photon computed tomography (SPECT). The study patients consisted of 11 children ranging in age from 3 to 14 years. Ten patients had significantly stenotic coronary arterial lesions due to Kawasaki disease, and one patient had a left coronary artery with an anomalous origin from the pulmonary artery. Evaluation was made before and after surgical revascularization in 3 patients. Regional myocardial perfusion was assessed at rest using 13N-ammonia, and regional myocardial glucose metabolism was assessed at rest under fasting conditions using 18F-fluorodeoxyglucose (18FDG). SPECT was performed after dipyridamole infusion. Initial and delayed images were obtained 7 min and 3 hrs after dipyridamole infusion, respectively. Left ventricular myocardial images were categorized as the septal, anterior, lateral, apical, and inferior segments, and evaluation was made for each segment. A total of 70 myocardial segments in 11 patients were classified into 4 groups according to the PET findings: 1) segments with normal perfusion and without enhanced 18FDG uptake (normal segments; n = 55), 2) normal perfusion with enhanced 18FDG uptake (metabolically abnormal segments; n = 3), 3) hypoperfusion with enhanced 18FDG uptake (ischemic but viable segments; n = 9), and 4) hypoperfusion without enhanced 18FDG uptake (non-viable segments; n = 3). On SPECT, the numbers of myocardial segments showing no perfusion defects, complete redistribution, incomplete redistribution, and persistent perfusion defects were 38, 12, 14, and 6, respectively. Comparisons were made between PET findings and SPECT findings.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1992

Viable myocardium identified by reinjection thallium-201 imaging: comparison with regional wall motion and metabolic activity on FDG-PET.

Reinjection thallium-201 scans were performed in 68 patients with coronary artery disease after the routine stress-delayed scans for more accurate identification of new fill-in. Following the stress and 3 hour delayed thallium-201 SPECT scans, 40 MBq (1.1 mCi) was injected at rest, and 10 min later, the reinjection SPECT scan was obtained. To determine whether the reinjection method can aid in identifying ischemic but viable myocardium, the thallium-201 findings were compared with regional wall motion on radionuclide ventriculography in 61 patients and with metabolic activity on positron emission tomography (PET) using F-18 fluorodeoxyglucose (FDG) in 18 patients. The reinjection scan identified new fill-in which had not been shown on the stress-delayed scans in 6 of the 22 patients (27%) or in 29 of the 105 segments (28%). Regional wall motion was preserved more in the segments that exhibited new fill-in after reinjection (wall motion score = 1.64 +/- 1.29) than in those without new fill-in (score = 2.72 +/- 1.04) (p < 0.01). In the comparative study with FDG-PET, persistent FDG uptake was observed in all segments with new fill-in (20/20 segments: 100%); whereas, it was seen in only 7 of the 28 segments (25%) without new fill-in after reinjection (p < 0.05). We concluded that the segments having new fill-in after reinjection may represent ischemic but viable myocardium. Thus, the reinjection thallium-201 scan should be performed to identify ischemic myocardium which occasionally cannot be detected by the routine stress-delayed thallium-201 scans.

Adult↗

PubMed1992

Effect of nebracetam on nicotinic and muscarinic acetylcholine receptors expressed in Xenopus oocyte by injecting exogenous mRNA.

Using voltage- and current-clamp methods the effects of nebracetam 4-aminomethyl-1-benzylpyrrolidine-2-one hemifumarate, WEB 1881 FU, CAS 118607-07-1), a new agent with nootropic property, on the nicotinic (nAChRs) and muscarinic acetylcholine receptors (mAChRs) were studied, which were expressed in Xenopus oocytes by injecting E. electricus mRNA and rat brain mRNA, respectively. Simultaneous application of nebracetam (0.03-2 mmol/l) with acetylcholine (ACh) (0.01-1 mmol/l) inhibited the ACh-responses of both nAChRs and mAChRs, whereas preapplication of these concentrations of nebracetam for 30 s to 1 min potentiated such inhibition. A simple competitive inhibition model for the effects of both drugs simultaneously applied yielded the inhibition constant, K1 of 0.419 and 0.212 mmol/l for nAChRs and mAChRs, respectively, indicating that the action on mAChRs is a little more potent than on nAChRs. Nebracetam induced a concentration-dependent slight increase in inward currents on mAChRs but not on nAChRs. It is suggested that the direct effects of nebracetam on nAChRs and mAChRS, which were induced only by a rather high concentration, as compared with the clinically expected plasma level, may be a contributing factor to the clinical effectiveness of the drug only if there is some critical change in the sensitivity to the drug.

Acetylcholine↗

PubMed1992

In vitro closing behavior of the St. Jude Medical heart valve in the pulmonary position. Valve incompetence originating in the prosthesis itself.

We examined the in vitro closing behavior of the St. Jude Medical heart valve, simulating (1) a low-pressure system, (2) the anatomic peculiarity of the right ventricular outflow tract and the main pulmonary artery, and (3) disturbed diastolic compliance of the right ventricle. The variables in the experiment were the load impedance to the pump and the valve orientation. The results were as follows. The sequence of closure of the two semidiscs was based on the valve orientation; reduction in impedance caused the semidisc that closed last to remain open, while the other semidisc continued its open-close motion; further reduction in impedance prevented the semidisc, which continued its open-close motion, from closing completely. These results highlight the forces involved in semidisc closure and the existence of a threshold of force for completion of semidisc closure. Further, the results demonstrate that under certain circumstances the threshold cannot be exceeded via those forces. Therefore this incompetence must originate in the prosthesis itself. In this regard, we suggest an urgent need to reconsider the indications for St. Jude Medical heart valve pulmonic implantation. Finally, we advocate the necessity for an in vitro assessment of valve prostheses in a low-pressure system, to evaluate the safety of right-sided placement.

Evaluation Studies as Topic↗

PubMed1992

[A case report of successful repair of an aortopulmonary fistula with partial dissection of the pulmonary artery].

We experienced a case of aortopulmonary fistula due to true thoracic aortic aneurysm. Surgical repair was electively performed when we found coexisting pulmonary arterial dissection. Under extracorporeal circulation, dissected flap was excised and the fistula was closed with his own pericardium, and his aortic arch and innominate artery were replaced with a piece of vascular prosthesis. His intra and post operative condition was stable, and postoperative course was uneventful. Prior to this case 13 surgically treated cases had been reported, and 5 had been successful. Among them, only 2 had been electively operated and both successful. Our case is the second case of aortopulmonary fistula associated with pulmonary arterial dissection.

Aortic Dissection↗

PubMed1992

Arterial ketone body ratio during and after cardiopulmonary bypass.

This study is the first to investigate the alteration in hepatic function during and after cardiopulmonary bypass in 30 patients by measuring the arterial ketone body ratio, an index of mitochondrial redox potential (oxidized nicotinamide-adenine dinucleotide/reduced nicotinamide-adenine dinucleotide). Although the preoperative arterial ketone body ratio was within normal limits (1.24 +/- 0.63), it decreased markedly 5 minutes after the start of cardiopulmonary bypass to 0.35 +/- 0.12 and remained at this low level throughout bypass. After bypass it continued to rise in a time-dependent fashion, returning to its preoperative level by the morning of the second postoperative day in normal convalescent patients. However, the ratio recovered more slowly in patients who required prolonged circulatory or respiratory support than in other patients. Thus we suggest that cardiopulmonary bypass had deleterious effects on the hepatic mitochondrial redox potential, which may contribute to homeostatic derangements and metabolic abnormalities.

Aged↗

PubMed1992

[Surgical therapy of aortic regurgitation due to aortitis syndrome--effectiveness and extended indication of Bentall's operation].

Fourteen patients with aortic regurgitation due to aortitis syndrome that underwent surgical therapy were studied with particular emphasis on the long term merits of Bentall's operations over the conventional valve replacement. They were divided into two groups; Group A: 6 aortic valve replacements (AVRs) and Group B: 8 Bentall's operations. Post operative complications related to aortitis syndrome developed in 3 cases; a case of paravalvular leakage (Group A) and two cases of aneurysm formation at the coronary artery anastomotic sites (Group B). We speculated that these complications were due to abnormal healing and recurrent inflammatory process of the disease. Therefore we think that conventional valve replacement is not suited to cope with these problems. Since 1984, we have adopted the policy to perform Bentall's operations for all patients with aortitis requiring valve replacement. Bentall's operation required longer aortic cross-clamp time (212.1 +/- 53.9 min) than AVRs (73.0 +/- 25.0) and was more aggressive. However no patients with our current technique to reimplant the coronary artery button and distal graft to aorta anastomosis, which has been used since 1984, has developed pseudoaneurysm or valvular leakage. We conclude that our modified Bentall's operation is effective even for patients who have active aortitis syndrome or need redo operations.

Adult↗

PubMed1991

Echocardiographic assessment of left ventricular function and wall motion at high altitude in normal subjects.

To understand the effects of high-altitude hypoxia on cardiac function and the change in cardiac function during high-altitude acclimatization, precise studies were first performed at greater than 5,000 m of altitude in Himalaya by 2-dimensional echocardiography. In addition to examining well-known indexes of cardiac function, the centerline method was used to assess regional wall motion, which has not been examined under conditions of high-altitude hypoxia. The subjects were 11 climbing members (aged 21 to 43 years) of the Kyoto University Medical Research Expedition of Xixabangma (8,027 m) in 1990. Examinations were performed at sea level, at the base camp (5,020 m), and twice at the advanced base camp (5,650 m). Heart rate, left ventricular (LV) end-diastolic volume, cardiac output, mean rate of circumferential fiber shortening, ejection fraction, % fractional shortening, and regional LV wall motion were measured. At high altitude, heart rate increased to 136% of the sea level value, but gradually decreased in the degree of increment at the early and late advanced base camp measurements. LV end-diastolic volume decreased significantly by 70%. At base camp there were significant increases in ejection fraction, mean rate of circumferential fiber shortening, and % fractional shortening, which showed little change during the long-term stay at high altitude. Regional wall motion at high altitude (measured by the center-line method) decreased at the septal wall and increased at the posterolateral wall. These results demonstrate that: (1) LV cardiac performance at high altitude is enhanced significantly in spite of reduced preload. After good acclimatization, cardiac performance remains augmented, but there is a tendency to decrease the degree of augmentation. (2) In regional LV wall motion, septal wall motion is impaired, but LV posterolateral wall motion shows a compensatory increase.

Acclimatization↗

PubMed1991

Further characterization of a high affinity thyrotropin binding site on the rat thyrotropin receptor which is an epitope for blocking antibodies from idiopathic myxedema patients but not thyroid stimulating antibodies from Graves' patients.

Cysteine 390 of the rat thyrotropin (TSH) receptor, when mutated to serine, results in a receptor with a reduced ability of TSH to bind and increase cAMP levels but a preserved ability of thyroid stimulating autoantibodies (TSAbs) from hyperthyroid Graves' patients to increase cAMP levels. The ability of receptor autoantibodies from hypothyroid patients with idiopathic myxedema to inhibit the TSAb activity which is preserved is, however, like TSH binding, significantly reduced. Cysteine 390, together with tyrosine 385, thus appears to be an important determinant in a high affinity TSH binding site which is an epitope for receptor autoantibodies which block TSH or TSAb action and cause hypothyroidism rather than TSAbs which increase cAMP levels and are associated with hyperthyroidism. Threonine 388 and aspartic acid 403 may contribute to this ligand interaction site.

Amino Acid Sequence↗