PubMed Health⌕ Search

Biomedical subjects

T Inui

Publications and source records attributed to T Inui.

At least 127 records · Page 7Linked to original sources
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

ETA and ETB receptors on single smooth muscle cells cooperate in mediating guinea pig tracheal contraction.

We investigated the distribution of endothelin A (ETA) and ETB receptors in single smooth muscle cells and their contribution to ET-induced contractions of guinea pig trachea. ETA and ETB receptors were detected in smooth muscle membranes (maximum binding capacities of 810 and 360 fmol/mg protein and dissociation constants of 38 and 5.1 pM for 125I-labeled ET-1 and 125I-ET-3, respectively) and visualized autoradiographically in primary cultured cells. ET-1 and ET-3 evoked concentration-dependent increases in intracellular Ca2+ concentration and smooth muscle tension. The half-maximally effective concentrations of ET-1 and ET-3 at inducing contractions were 1.9 and 2.7 nM, respectively. The Ca2+ responses showed tachyphylaxis to both ETs after stimulation with ET-1, but only to ET-3 after stimulation with ET-3. Consecutive applications of ET-3 and ET-1 (10 nM each) classified the cells into ETA dominant (approximately 30%) responding to only ET-1, ETB dominant (approximately 20%) responding to only ET-3, and ETA- and ETB-possessing (approximately 50%) cells responding to both. The ETA antagonist, 10 microM BQ-123, attenuated ET-1-induced contractions but did not affect the ET-3-induced contractions. The results indicate that both receptors coexist in a major population of smooth muscle cells and cooperate in mediating ET-1-induced contractions.

Animals↗
PubMed1994

Structure-activity relationship of adrenomedullin, a novel vasodilatory peptide, in cultured rat vascular smooth muscle cells.

Vascular smooth muscle cells (VSMC) from rat aorta possess specific receptors for a novel potent vasorelaxant peptide, adrenomedullin (AM). To elucidate its receptor coupling to guanine nucleotide-binding stimulatory protein and the structural requirement of the AM molecule to its vascular receptors, we have studied the effects of guanine nucleotides on [125I]human (h) AM binding and adenylate cyclase activity in cultured rat VSMC, and the effects of various synthetic hAM analogs on [125I]hAM binding and the cAMP response. Guanosine 5'-O-(3-thiotriphosphate) dose dependently inhibited [125I]hAM binding to rat VSMC membranes. hAM stimulated adenylate cyclase activity, and its effect was additive with GTP. hAM-induced cAMP formation was abrogated by pretreatment with cholera toxin, but not by that with pertussis toxin. Intact hAM-(1-52)-NH2 and N-terminal truncated derivatives [hAM-(13-52)-NH2, hAM-(16-52)-NH2] almost equally inhibited [125I]hAM binding and stimulated cAMP formation, whereas removal of C-terminal Tyr52 residue [hAM-(1-51)-NH2] remarkably decreased receptor-binding activity and the cAMP response. The effects of hAM-(1-52)-OH, hAM-(1-51)-OH, and a linear hAM analog ([carbamoylmethyl-Cys16,21]hAM-NH2) were far less potent on receptor binding and the cAMP response than that of hAM-(1-52)-NH2. The C-terminal fragment [hAM-(33-52)-NH2] and the N-terminal fragment [hAM-(1-10)-OH] had neither receptor-binding nor adenylate cyclase activity. hAM-(22-52)-NH2 had no agonistic effect, but showed an antagonistic effect on the hAM-induced cAMP response. These data suggest that vascular AM receptors are functionally coupled to adenylate cyclase via guanine nucleotide-binding stimulatory protein. Studies of the structure-activity relationship of hAM revealed that the cyclic structure formed by the disulfide bridge and amidation of the C-terminal residue of the AM molecule are critical for receptor binding and subsequent cAMP generation and suggest that the C-terminal fragment hAM-(22-52)-NH2 may be an antagonist for vascular AM receptors.

Adenylate Cyclase Toxin↗
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↗
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

Contraction of smooth muscle by activation of endothelin receptors on autonomic neurons.

Endothelin receptors, predominantly of the ETB type, were localized to cell bodies, processes, and varicosities of cholinergic and adrenergic intramural autonomic neurons that were present in primary cultures of guinea pig tracheal smooth muscle. Stimulation of the neuronal ETB receptor produced a tetrodotoxin-sensitive increase in the intracellular calcium concentration in neurons which was followed by contraction of the neighboring smooth muscle cells. These observations suggest that endothelins can induce smooth muscle contraction by means of a neuronally mediated mechanism, in addition to their direct actions on the smooth muscle.

Animals↗
PubMed1993

Decrease in urinary excretion of 3-methylhistidine by patients with Duchenne muscular dystrophy during glucocorticoid treatment.

Seven patients, aged 10-17 years, with Duchenne muscular dystrophy were treated orally with prednisolone (PSL) at a dose of 0.8-1.0 mg/kg per day for 8 weeks. During the treatment their muscle strength, serum creatine kinase (CK) activity, serum levels of myoglobin (Mb), and urinary excretion of 3-methylhistidine (3-MeH) and glycine (Gly) were measured serially. In all the patients, the motor function or muscle strength improved, and the serum CK activity and Mb level decreased during PSL treatment. Urinary excretion of 3-MeH, a unique constituent of muscle contractile proteins, decreased to 51-63% of the baseline value in weeks 6-9 after the start of PSL administration, and returned to the baseline level in week 12. The ratios of 3-MeH to creatinine and to Gly also decreased during the treatment. Urinary excretion of Gly, which is ubiquitous in all tissues including muscle, did not decrease during the treatment. These findings suggest that PSL inhibits proteolysis of muscle contractile protein.

Adolescent↗
PubMed1993

Calcitonin gene-related peptide: a neurotransmitter involved in capsaicin-sensitive afferent nerve-mediated gastric mucosal protection.

Calcitonin gene-related peptide (CGRP), a potent vasodilating peptide, is present in primary afferent neurons of the gastric mucosa. However, its functional role in the stomach is not well established. The present study was undertaken to elucidate the involvement of gastric CGRP in the mechanism of protection against mucosal damage. Newborn Wistar rats were made CGRP-deficient by intraperitoneal injection of a sensory neurotoxin, capsaicin. All the experiments were performed 2.5 months after birth. The formation of mucosal lesions by administration of indomethacin to CGRP-deficient rats was significantly enhanced in comparison with that in normal rats. Intragastric administration of capsaicin significantly reduced the indomethacin-induced gastric mucosal lesions in normal rats. Pretreatment with a CGRP antagonist abolished the protective action of intragastric capsaicin against damaging agents. In isolated perfused stomach from normal rats, acute arterial infusion of capsaicin significantly reduced the perfusion pressure of the left gastric artery, with a simultaneous increase in CGRP and somatostatin secretion. The reduction of perfusion pressure and the increase of somatostatin secretion were inhibited by concomitant administration of a CGRP antagonist. In contrast, capsaicin infusion had no effect in CGRP-deficient rats. These results suggest that CGRP in the stomach plays a pivotal role in protection against gastric mucosal damage by indomethacin, possibly through an increase in gastric blood flow and somatostatin secretion.

Afferent Pathways↗
PubMed1993

Significance of endothelial deposition of von Willebrand factor in thrombotic thrombocytopenic purpura: autopsy findings of a case complicated with systemic lupus erythematosus.

We report the renal immunohistochemical findings of a patient with thrombotic thrombocytopenic purpura complicated with systemic lupus erythematosus. Aggregated platelets were observed adhering to the arteriole walls. Intense deposition of von Willebrand factor (vWF) was noted in the endothelium, even in areas where thrombi were not seen. This difference in the distribution of platelets and vWF suggested that the endothelium was damaged prior to platelet aggregation.

Aged↗
PubMed1992

Primary care physicians' response to domestic violence. Opening Pandora's box.

OBJECTIVE: To explore primary care physicians' experiences with domestic violence victims to determine the barriers to problem recognition and intervention in the primary care setting. DESIGN: Ethnography, a qualitative research method involving the use of open-ended, semistructured interviews. SETTING: An urban health maintenance organization serving a predominantly white, middle-income population. PARTICIPANTS: Thirty-eight physicians, predominantly family practitioners (89%), were interviewed. RESULTS: Analysis of the interviews revealed that physicians found exploring domestic violence in the clinical setting analogous to "opening Pandora's box." Their issues include lack of comfort, fear of offending, powerlessness, loss of control, and time constraints. CONCLUSION: This study revealed several barriers that physicians perceived as preventing them from comfortably intervening with domestic violence victims. These issues need to be addressed in training programs. Further studies should be done to assess generalizability of these findings to other groups of physicians.

Attitude of Health Personnel↗
PubMed1992

A potent and specific agonist, Suc-[Glu9,Ala11,15]-endothelin-1(8-21), IRL 1620, for the ETB receptor.

A series of C-terminal linear peptides of endothelin (ET)-1 and their N alpha-succinyl (Suc) analogs were synthesized and their binding affinities for the two subtypes of ET receptor, ETA and ETB, in porcine lung membranes were examined. Among the synthetic analogs, Suc-[Glu9,Ala11,15]-ET-1(8-21), IRL 1620, was the most potent and specific ligand for the ETB receptor (KiETA/KiETB approximately equal to 120,000) as judged by the Ki values for ETA (1.9 microM) and ETB (16 pM) receptors. IRL 1620 was 60 times more selective for the ETB receptor than ET-3 (KiETA/KiETB approximately equal to 1,900). IRL 1620 (10(-9)-10(-7) M) induced contractions of the guinea pig trachea with a comparable potency to those of ET-1 or ET-3, suggesting that IRL 1620 is a potent ETB receptor agonist.

Amino Acid Sequence↗
PubMed1992

Endothelin stimulates both cAMP formation and phosphatidylinositol hydrolysis in cultured embryonic bovine tracheal cells.

Embryonic bovine tracheal (EBTr) cells were found to possess receptors for endothelin (ET) of ET-1-selective (ETA) subtype with a Kd for ET-1 of 114 pM and a Bmax of 12.9 fmol/10(5) cells. Stimulation of EBTr cells with 100 pM to 100 nM ET-1 increased the contents of both inositol phosphates and cAMP in a concentration-dependent manner, indicating that the receptors are coupled to both phosphatidylinositol hydrolysis and cAMP formation in EBTr cells.

Animals↗
PubMed1992

Autocrine receptors for endothelins in the primary culture of endothelial cells of human umbilical vein.

Human umbilical vein endothelial cells (HUVECs) in primary culture produced and secreted endothelin 1 (ET-1) actively. Specific binding of [125I]ET-1 to these cells was not detectable because of the saturation of ET receptors with endogenously produced ET-1. However, addition of phosphoramidon, an inhibitor of ET-converting enzyme, to the medium reduced the production of ET-1 and thus the receptors on HUVECs were made available for exogenously added [125I]ET-1. Binding studies using phosphoramidon-treated HUVECs indicated the existence of a non-isopeptide-selective type (ETB) of ET receptor with a Kd of 17 pM. This receptor is thought to be involved in ET-induced vasodilation in an autocrine manner in vivo.

Binding Sites↗
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

HTLV-I infection in patients with autoimmune thyroiditis (Hashimoto's thyroiditis).

To investigate the possible relationship of HTLV-I virus infection to autoimmune thyroid disease, we examined, firstly, the frequency of HTLV-I seropositivity among patients with Hashimoto's thyroiditis and, secondly, the frequency of Hashimoto's thyroiditis in patients with HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP). Of 144 patients with Hashimoto's thyroiditis in the Tokushima and Kochi Prefectures, Japan, 9 (6.3%) were positive for serum HTLV-I virus antibody 2 of whom were confirmed histologically to have Hashimoto's thyroiditis. This percentage is significantly higher (P < 0.01) than the estimated prevalence (2.2%) of HTLV-I carriers among the general population in this region. Of 9 patients with HAM/TSP, 3 (33.3%), including 2 biopsy-proven cases, had evidence of Hashimoto's thyroiditis. This proportion is apparently much higher than the prevalence (1.7%) of Hashimoto's thyroiditis in the general population. These findings suggest that HTLV-I virus may be related to the development of Hashimoto's thyroiditis.

Adult↗
PubMed1992

[MCNS, which secondary developed into incidental IgA nephropathy--a case report].

There have been a number of case reports on nephrotic syndrome with histological findings of minimal change on light microscopy and mesangial IgA deposition on fluorescent microscopy. The pathogenesis of these cases is, however, yet to be clarified. Here, we report a case of minimal change nephrotic syndrome (MCNS) associated with IgA nephropathy, which developed later in the course of MCNS. The patient was 18 years old male with steroid-responsive nephrotic syndrome. First episode of proteinuria occurred when he was 4 years old. On the fourth episode of proteinuria, renal biopsy revealed minimal change on light microscopy and no evidence of deposition of immunoglobulins or complements on immunofluorescent and electron microscopy. On the fifth relapse of MCNS, microhematuria developed concomitantly with massive proteinuria. Renal biopsy, then, showed light microscopic findings of mild focal segmental glomurulonephritis. Significant mesangial IgA deposition was observed on immunofluorescence study. Electron microscopy revealed electron dense deposit in the mesangial and paramesangial area. The patient was well-responsive to steroid although microhematuria persisted after disappearance of proteinuria. We concluded that IgA nephropathy may have developed subsequently in the course of MCNS in our case.

Adolescent↗