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Biomedical subjects

M Inada

Publications and source records attributed to M Inada.

At least 73 records · Page 4Linked to original sources

Thyroxine (T4) metabolism in an athyreotic patient who had taken a large amount of T4 at one time.

As we had an opportunity to take blood samples from a totally thyroidectomized patient who had attempted suicide by taking 2,000 microg of Levothyroxine (L-T4), the serum levels of thyroid hormones were sequentially measured to investigate the metabolism of circulating thyroid hormones in an athyreotic human. The serum concentrations of most thyroid hormones reached a peak on the second day, but the serum T3 level showed a peak one day later. The maximum concentrations of T4 (315 microg/l), FT4 (48.8 ng/l) and rT3 (0.80 microg/l) were very high, while the peak T3 level (1.92 microg/l) did not exceed the upper limit of the normal range. The serum T4 and rT3 levels returned to their normal range 13-17 days after the suicide attempt. The TSH level was suppressed rapidly and reached its nadir (0.044 mU/l) on the 6th day. During this period, the T1/2 and MCR of serum T4 were 10.4 days and 0.64 l/day, respectively, which values were almost equivalent to those observed during 15 days after discontinuation of the maintenance L-T4 therapy. In summary, the oral intake of a large amount of L-T4 at one time does not induce a proportional increase in the T3 level in an athyreotic person. The MCR of serum T4 is decreased and the T1/2 of serum T4 is prolonged, probably due to the lack of intrathyroidal deiodination. These findings support the conclusion that the D1 activity in the thyroid is one of the major determinants in the metabolic clearance of serum T4.

Adult↗

Variant angina in isolated adrenocorticotropin deficiency, inappropriate vasopressin secretion and Hashimoto's thyroiditis.

We report a 62-year-old male patient who had variant angina and isolated adrenocorticotropic hormone (ACTH) deficiency. His serum sodium concentration was low and vasopressin was inappropriately high for the low plasma osmolality. Serum free thyroxine (FT4) was low and thyroid stimulating hormone (TSH) was high with positive anti-thyroperoxidase antibodies, compatible with Hashimoto's thyroiditis. Treatment with Amrodipine and hydrocortisone relieved chest symptoms and hyponatremia, and hypothyroidism was also normalized. It is suggested that coronary artery spasm may be related to cortisol deficiency and/or inappropriately high vasopressin secretion and that hypothyroidism was ameliorated because the reduced responsiveness to TSH returned to normal due to hydrocortisone supplement.

Adrenocorticotropic Hormone↗

[Coenzyme Q10].

Explore the source record for details and available documents.

Coenzymes↗

[Vasopressin type 2 receptor mutations in congenital diabetes insipidus].

Congenital nephrogenic diabetes insipidus is a rare inherited disorder, which is characterized by the inability of the kidney to concentrate urine due to unresponsiveness to antiduretic hormone arginine vasopressin. Defects must be present somewhere in a vasopressin signal transduction pathway in kidney collecting duct. Recent genetic analysis demonstrated that mutations in vasopressin type 2 receptor and water channel aquaporin 2 are responsible for x-linked and autosomal recessive form, respectively. Expression studies of mutant proteins showed that most of the mutations cause severe functional defects, which are compatible with clinical phenotypes. These advances help understanding of molecular mechanism underlying this disease and therefore improve diagnostic and therapeutic approaches.

Animals↗

[Pathophysiological function of angiotensin II AT1 and AT2 receptors and clinical application of AT1 antagonists].

Angiotensin II (Ang II) receptors are classified into two subtypes, type 1 (ATF-R) and type 2 (AT2-R) by development of non-peptidic antagonists. Classical Ang II function including vasopressor effect, cardiotropic action and aldosterone production is mainly mediated through AT1-R that present in cardiovascular system, adrenal glands and kidneys. AT1-R is abundantly expressed in whole bodies of fetus and its expression is abruptly decreased after birth, and in the adult AT2-R is expressed in brain nuclei, uterus, adrenal medullary glands and ovary. AT1-R and AT2-R are both G-protein coupled receptors and have 46% similarity in amino acid levels with seventh transmembrane conformation. Signal transduction pathway of AT1-R is mainly CA2+ and activation of protein kinase C, while that of AT2-R is still unknown. Clinical application of AT1-R antagonist started and this causes elevation of plasma Ang II levels, which selectively stimulates AT2-R. Thus, one should realize AT2-R-mediated effect in treatment with AT1-R antagonist. We have shown that AT2-R has anti-AT1-R action, such as inhibitory action against AT1-R-mediated positive chronotropic effect or AT1-R-induced proliferative effect, resulting in the protective effects on Ang II-induced cardiovasucular and renal action. Thus, elucidation of AT2-R function will be important in clinical treatment with AT1-R antagonists.

Angiotensin II↗

[Immune complex-mediated glomerulonephritis associated with infective endocarditis with aortic valve vegetation].

A 61-year-old male was referred to our hospital for rapidly progressive azotemia. He was also found to have huge vegetation at the aortic valve causing regurgitation. Biochemical examinations revealed the presence of an immunocomplex associated with decreased circulating complements. In biopsy samples from the kidney, we found the presence of fibrillar crescents, proliferation of mesangial cells, increase in extracellular matrix proteins, atrophy of tubules, infiltration of mononuclear cells in the interstitial regions, high density deposits in the mesangial area and mesangial interposition. Since the patient strongly rejected operative treatment by valvular replacement, we continued non-invasive treatment such as hemodialysis and treatment with penicillin G. This transiently improved the condition of the patient, including biochemical data and cardiac function, but there was no reduction in the size of vegetation at the aortic valve and the bacteria responsible for infective endocarditis were not identified. About three months after admission, overt signs of congestive heart failure emerged and the patients was subjected to intensive care with a respirator and hemodynamic monitoring. Although the cardiac function was improved, concomitant severe pneumonia occurred and the patient died of septic shock. Thus, we report a rare case in whom immune complex-mediated glomerulonephritis was associated with infective endocarditis with aortic valve vegetation.

Antigen-Antibody Complex↗

Effect of cilostazol on soluble adhesion molecules and platelet-derived microparticles in patients with diabetes.

We evaluated the plasma concentrations of soluble adhesion molecules and platelet-derived microparticles (PMP) in patients with non-insulin dependent diabetes mellitus (NIDDM) and studied the effect of cilostazol on PMP generation. There were differences in the levels of soluble adhesion molecules between NIDDM patients (N = 43) and the control subjects (N = 30) (soluble thrombomodulin: 11.5+/-5.3 vs. 7.0+/-1.2 TU/ml, p<0.0001; soluble vascular cell adhesion molecule-1: 708+/-203 vs. 492+/-113 ng/dl, p<0.0001; soluble intercellular cell adhesion molecules- 1: 274+/-65 vs. 206+/-48 ng/dl, p<0.0001; soluble P-selectin: 194+/-85 vs. 125+/-43 ng/dl, p<0.0001). There were also differences in the levels of PMP and platelet activation markers between NIDDM patients and the controls (PMP: 943+/-504 vs. 488+/-219/10(4) plt, p<0.0001; platelet CD62P: 9.2+/-4.6 vs. 4.4+/-4.3%, p<0.001; platelet CD63: 10.2+/-4.5 vs. 4.5+/-3.3%, p<0.0001; platelet annexin V: 9.1+/-3.9 vs. 5.3+/-3.8%, p<0.001). To study the release of PMP into plasma, a modified cone-and-plate viscometer was used. Increased release of PMP from platelets was observed in diabetic plasma compared to normal plasma under high shear stress conditions (2,672+/-645 vs. 1,498+/-386/10(4) plt, p<0.05). Therefore, one cause of PMP elevation in NIDDM may be high shear stress. The levels of PMP, activated platelets, and soluble adhesion molecules all decreased significantly after treatment with cilostazol. These results suggest that cilostazol may be useful for the inhibition of both PMP-dependent and -independent vascular damage in NIDDM.

Adult↗

Angiotensin type 2 receptors are reexpressed by cardiac fibroblasts from failing myopathic hamster hearts and inhibit cell growth and fibrillar collagen metabolism.

BACKGROUND: Angiotensin (Ang) II type 1 receptor (AT1-R) induces cardiomyocyte hypertrophy and fibroblast proliferation, whereas the physiological role of AT2-R in cardiac remodeling remains poorly defined. METHODS AND RESULTS: Using Bio14.6 cardiomyopathic (CM) hamsters, we found that AT2-R sites were increased by 153% during heart failure compared with F1B controls. AT1-R numbers were increased by 72% in the hypertrophy stage and then decreased to the control level during heart failure. Such differential regulation of AT2-R and AT1-R during heart failure was consistent with changes in the respective mRNA levels. Autoradiography and immunocytochemistry revealed that both AT2-R and AT1-R are localized at higher densities in fibroblasts present in fibrous regions. Surrounding myocardium predominantly expressed AT1-R, but the level of expression was less than that in fibrous regions. Cardiac fibroblasts isolated from CM hearts during heart failure but not from control hamsters expressed AT2-R (30 fmol/mg protein). Using the cardiac fibroblasts expressing AT2-R, we found that Ang II stimulated net collagenous protein production by 48% and pretreatment with an AT2-R antagonist, PD123319, evoked a further elevation (83%). Ang II-induced synthesis of fibronectin and collagen type I were enhanced by 40% and 53%, respectively, by pretreatment with PD123319. Ang II-induced DNA synthesis (assessed by [3H]thymidine uptake) was significantly increased by PD123319, and the AT2-R agonist CGP42112A reduced the serum-stimulated increase in cell numbers by 23%. Treatment with an AT1-R antagonist, TCV116, for 20 weeks inhibited progression of interstitial fibrosis by 28%, whereas with 44-week PD123319 treatment but not 20-week treatment, the extent of the fibrous region was increased significantly, by 29%. CONCLUSIONS: These findings demonstrate that AT2-R is re-expressed by cardiac fibroblasts present in fibrous regions in failing CM hearts and that the increased AT2-R exerts an anti-AT1-R action on the progression of interstitial fibrosis during cardiac remodeling by inhibiting both fibrillar collagen metabolism and growth of cardiac fibroblasts.

Angiotensin Receptor Antagonists↗

Increased B-lymphopoiesis by interleukin 7 induces bone loss in mice with intact ovarian function: similarity to estrogen deficiency.

Estrogen deficiency caused by ovariectomy (OVX) results in a marked bone loss due to stimulated bone resorption by osteoclasts. During our investigations of the pathogenesis of bone loss in estrogen deficiency, we found that OVX selectively stimulates B-lymphopoiesis which results in marked accumulation of B220-positive pre-B cells in mouse bone marrow. To examine the possible correlation between stimulated B-lymphopoiesis and bone loss, 8-week-old female mice were treated with interleukin (IL) 7, which stimulates B-lymphopoiesis in bone marrow. We also examined bone mass in IL-7 receptor-knockout mice that exhibit marked suppression of B-lymphopoiesis in the bone marrow. The increased B-lymphopoiesis induced by IL-7 administration resulted in marked bone loss by stimulation of osteoclastic bone resorption in mice with intact ovarian function. The changes in both B-lymphopoiesis and bone mass in IL-7-treated female mice were similar to those in age-matched OVX mice. In contrast, the trabecular bone volume of the femur was greatly increased in both female and male IL-7 receptor-knockout mice when compared with the respective wild-type and heterozygous littermates. These results show that the perturbation of B-lymphopoiesis in the bone marrow is closely linked to the change in bone mass. We propose here that the increased B-lymphopoiesis due to estrogen deficiency is involved in the mechanism of stimulated bone resorption.

Animals↗

Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts.

A transcription factor, Cbfa1, which belongs to the runt-domain gene family, is expressed restrictively in fetal development. To elucidate the function of Cbfa1, we generated mice with a mutated Cbfa1 locus. Mice with a homozygous mutation in Cbfa1 died just after birth without breathing. Examination of their skeletal systems showed a complete lack of ossification. Although immature osteoblasts, which expressed alkaline phophatase weakly but not Osteopontin and Osteocalcin, and a few immature osteoclasts appeared at the perichondrial region, neither vascular nor mesenchymal cell invasion was observed in the cartilage. Therefore, our data suggest that both intramembranous and endochondral ossification were completely blocked, owing to the maturational arrest of osteoblasts in the mutant mice, and demonstrate that Cbfa1 plays an essential role in osteogenesis.

Animals↗

Effect of cilostazol in preventing restenosis after percutaneous transluminal coronary angioplasty.

This study sought to evaluate the effect of cilostazol in preventing restenosis after successful percutaneous transluminal coronary angioplasty (PTCA) in 68 patients: 35 patients received cilostazol immediately after PTCA and 33 patients received aspirin or ticlopidine. Repeat coronary angiography was performed 4 to 6 months after PTCA and the incidence of restenosis was significantly lower (17%) in the cilostazol group than in the non-cilostazol group (40%) (p < 0.05), which indicates that cilostazol has the potential to prevent restenosis after PTCA.

Aged↗

Resolution of late potentials with improvement in left ventricular systolic function in patients with first acute myocardial infarction.

BACKGROUND: Ventricular late potentials predict subsequent arrhythmic events and sudden death in postinfarction patients. Late potentials are recorded in the infarcted area, but it should be pointed out that they probably represent micropotentials in the area of delayed conduction found among isolated areas of scar tissue and normal myocardium. HYPOTHESIS: The study was undertaken to investigate the relationship between chronic reversible myocardial ischemia, such as stunned or hibernating myocardium, and late potentials in 38 patients with a first myocardial infarction. METHODS: The patients were divided into two groups, one with (Group 1) and one without (Group 2) resolution of late potentials recorded by signal-averaged electrocardiogram at 6 months after onset of myocardial infarction. We investigated the clinical, echocardiographic, and signal-averaged electrocardiographic characteristics of Groups 1 and 2. RESULTS: In the chronic phase of myocardial infarction, a higher incidence of patency of the infarct-related artery and an improvement of wall motion score were found in Group 1, and left ventricular ejection fraction was better preserved in Group 1 than in Group 2. CONCLUSIONS: These results suggest that the resolution of late potentials was influenced by the improvement of left ventricular systolic function and patency of the infarct-related artery. We concluded that chronic reversible myocardial ischemia, such as stunned or hibernating myocardium, might be the substrate that generated late potentials.

Action Potentials↗

Successful treatment of a patient with Graves' disease on hemodialysis complicated by antithyroid drug-induced granulocytopenia and angina pectoris.

We report here a patient with recurrent Graves' disease on hemodialysis. She also suffered from angina pectoris, which was probably a manifestation of Graves' disease due to the increased oxygen demands in the presence of fixed coronary lesions. Although antithyroid drugs induced mild granulocytopenia, propylthiouracil (PTU) or methimazole (MMI) was not discontinued during the administration of granulocyte colony-stimulating factor (G-CSF). The patient received sodium iodine-131 therapy, and became euthyroid with no chest pain. To our knowledge, this is the first case that illustrated the usefulness of G-CSF for antithyroid drug-induced granulocytopenia prior to thyroid ablation for Graves' disease complicated with chronic renal failure and angina pectoris.

Agranulocytosis↗

Paracrine effect of human chorionic gonadotropin ectopically produced from papillary thyroid cancer cells on growth and function of FRTL-5 rat thyroid cells.

It is well known that human chorionic gonadotropin (hCG) is sometimes secreted from nontrophoblastic neoplasms. To elucidate the role of ectopic hCG, we investigated the effect of hCG produced from a papillary thyroid cancer cell line (B-CPAP cells) on stimulation and growth promotion of FRTL-5 rat thyroid cells. Ectopic hCG contained in the culture medium of B-CPAP cells was purified using gel filtration and bioassayed for thyrotropic activity in FRTL-5 cells. Addition of ectopic hCG (up to 5.2 x 10(4) IU/L) increased cyclic adenosine monophosphate (cAMP) accumulation and 3H-thymidine incorporation in FRTL-5 cells dose dependently. These effects were almost as potent as the stimulation induced by standard hCG CR-127. After the absorption of the ectopic hCG by anti-hCG-beta monoclonal antibody, the cAMP accumulation was significantly decreased. Analysis of ectopic hCG isoforms with different isoelectric points indicated the predominance of the acidic hCG isoform with isoelectric point (pI) 3.8-3.2 that is the major isoform of standard hCG. Basic isoforms (pI 5.7-5.3) with higher thyrotropic potency were also detected. These results indicate that the ectopic hCG secreted from papillary thyroid cancer cells possess intrinsic thyroid-stimulating and growth-promoting activity. The ectopic hCG may act as an autocrine-paracrine factor in nontrophoblastic neoplasms.

Animals↗

Longitudinal dissociation in the his bundle: a possible mechanism of two distinct cycle lengths in atrioventricular reentrant tachycardia.

Two wide QRS tachycardias with identical morphology but different cycle lengths (CLs) developed in a 63-year-old man. Electrophysiological study demonstrated inducible atrioventricular reentrant tachycardia (AVRT) due to a concealed left posterior accessory pathway (AP), which was successfully ablated by radiofrequency application. Neither dual AV nodal pathways nor other APs were documented. Splitting of the His-bundle electrogram was shown, and programmed stimulation induced sudden prolongation of intra-hisian conduction time. These results suggest longitudinal dissociation in the His bundle may be responsible for two distinct CLs in AVRT without dual AV nodal physiology.

Bundle of His↗

Effects of platelet-activating factor on left ventricular performance in dogs.

To elucidate the mechanism by which platelet-activating factor (PAF) decreases cardiac output (CO), its effects on left ventricular (LV) performance were studied using a LV pressure-volume model in 9 anesthetized dogs. LV volume was measured with a conductance catheter and LV pressure with a manometer-tipped catheter. The slopes of the end-systolic pressure-volume (Ees), stroke work-end-diastolic volume (Mw), and arterial end-systolic pressure-stroke volume relations (Ea), and of end-diastolic pressure-volume relations (EDPVRs), were obtained to evaluate changes in LV performance. The time constant of isovolumetric relaxation (T) was computed by a logarithmic and a derivative method. After intravenous administration of PAF (1 microgram/kg), LV end-diastolic volume and pressure, end-systolic pressure, maximum dP/dt and CO decreased. Ees and Mw decreased significantly, minimum dP/dt decreased, and T increased. The arterial end-systolic pressure-stroke volume relation shifted leftward with an increase in the slope (Ea), whereas EDPVRs were shifted to the left and superimposed on their potential passive diastolic properties. These findings indicate the PAF decreases CO by reducing preload and contractility and by increasing arterial load. However, despite a prolongation of relaxation, PAF may not affect passive diastolic chamber stiffness.

Animals↗

Coexistence of an autonomously functioning thyroid nodule in a patient with Graves' disease: an unusual presentation of Marine-Lenhart syndrome.

A 44-year-old woman developed hyperthyroidism due to the coexistence of Graves' disease and an autonomously functioning thyroid nodule (AFTN). Anti-thyrotropin receptor antibody (TRAb) was strongly positive (83.2%), and a thyroid scan initially showed diffuse uptake of Tc-99m pertechnatate in both lobes and further increased uptake in accordance with the right lobe nodule. The nodule in the right lobe was histologically diagnosed as thyroid follicular adenoma. After she was maintained in a euthyroid state by treatment with Methymazole (MMI), thyroid uptake of Tc-99m in the nodule became lower and was slightly suppressed by T3 administrations probably due to its dependence on TSH. Subtotal thyroidectomy was performed and she subsequently became euthyroid with negative TBII activity. It is concluded that she had a coexisting functioning nodule with Graves' disease (Marine-Lenhart syndrome) and that the nodule changed from hot to cool along with the anti-thyroid treatment, unlike usual cases of this syndrome showing a cold nodule on the initial imaging under the hyperthyroid state. Repeated Tc-99m pertechnatate thyroid scans were helpful in evaluating the reaction of MMI and TSH in both lesions separately in the present case.

Adenoma↗

Simultaneous xenotransplantation of human Graves' thyroid tissue and autologous bone marrow cells in severe combined immunodeficient mice: successful reconstitution of human Graves' hyperthyroidism.

Human thyroid xenografts and the autologous bone marrow (BM) cells from five patients with Graves' disease (GD) were simultaneously xenografted into severe combined immunodeficient (SCID) mice to study the role of BM cells for the perpetuation of human GD autoimmunity and hyperthyroidism. All SCID mice engrafted with thyroid tissue (TH) alone, TH + autologous peripheral blood mononuclear cells, and TH + autologous BM cells produced similar amounts of human IgG; however, the production in TH + BM-engrafted mice peaked later than that of mice without BM. Production of thyroperoxidase antibody and thyroglobulin antibody in TH + BM-bearing SCID mice peaked in later weeks after xenografting than in those without BM. Moreover, human Graves' hyperthyroidism was actually reconstituted in TH + BM-transplanted mice; this was confirmed by (A) significantly higher levels and longer periods of secreting thyroid-stimulating antibody than those in mice without BM engraftment. (B) persistent hyperthyroxinemia up to the end of the experiment. (C) extremely high radioidine uptake of the xenografted thyroid tissue, and (D) histological findings of the maintenance of hyperplastic change of the xenografted thyroid epithelial cells. Human BM stem cells (CD34) were identified only in mice with TH + BM xenografts when analyzed by immunohistochemistry. In conclusion, (A) we have developed an animal model for human hyperthyroid GD by simultaneous xenotransplantation of GD thyroid tissue plus autologous BM cells into SCID mice, and (B) BM cells have a crucial role for perpetuating human GD autoimmunity and hyperthyroidism in this system.

Adult↗