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Biomedical subjects

K Nonaka

Publications and source records attributed to K Nonaka.

At least 19 recordsLinked to original sources

Presynaptic facilitation of excitatory postsynaptic potential by glucagon in neurons of rat ventromedial hypothalamic slices.

Intracellular recordings were made from neurons in rat ventromedial hypothalamus (VMH), in vitro. Application of glucagon (100 nM to 5 microM) for 2-5 min increased the amplitude of excitatory postsynaptic potential (EPSP) lasting for 10-20 min. Forskolin and 8-bromo-cyclic AMP mimicked glucagon in producing a long-lasting facilitation of the EPSP. These drugs did not affect depolarizing response produced by glutamate. 3-Isobutyl-1-methylxanthine (IBMX) potentiated the time course of glucagon-induced facilitation of the EPSP. These results suggest that glucagon facilitates the EPSP probably by increasing transmitter release through activation of adenylate cyclase.

Animals

[Prediction for effectiveness of steroid pulse therapy by MRI in Graves' ophthalmopathy].

Fifteen patients with Graves' ophthalmopathy (GO) were treated with intravenous methylprednisolone (steroid pulse therapy, 1g daily for 3 days a week, 2-4 times) and followed up by ophthalmological assessment and magnetic resonance imaging (MRI). The signal intensity of enlarged eye muscle and retrobulbar fat was examined with MRI at 0.5T with short inversion time inversion recovery (STIR) sequences. The signal intensity of eye muscle and retrobulbar fat tissue in STIR was evaluated as the ratio to cerebral substantia alba (signal intensity ratio). The thickness of enlarged eye muscle was measured by T1-weighted coronal images. The signal intensity ratios of enlarged eye muscle of GO patients were significantly higher than those of eight normal subjects. Although the signal intensity ratios of muscle and retrobulbar fat before therapy were not related to the severity of clinical findings of GO assessed by ophthalmopathy index, the initial signal intensity ratios of eye muscle and retrobulbar fat of ten patients with improved clinical findings of GO after steroid pulse therapy tended to be higher than those of five patients without improvement by the therapy. After the therapy the signal intensity ratios of muscle and retrobulbar fat were significantly decreased in ten patients with favorable response. Our data suggested that high signal intensity in STIR may reflect edema caused by acute inflammation associated with GO. In conclusion, MRI may be a useful tool for determining the indication and prognosis of steroid pulse therapy. We strongly recommend measuring the signal intensity of eye muscle as well as muscle thickness in MRI to evaluate the activity of GO.

Adipose Tissue

Inhibitory effects of nicotinamide on recombinant human interferon-gamma-induced intercellular adhesion molecule-1 (ICAM-1) and HLA-DR antigen expression on cultured human endothelial cells.

Intercellular adhesion molecule-1 (ICAM-1), HLA-A, B, C and HLA-DR antigen on endothelial cells (EC) play important roles in the development of inflammatory processes in autoimmune disorders. In the present study, we investigated the effect of nicotinamide, an inhibitor of poly(ADP ribose) synthetase, on interferon-gamma (IFN gamma)-induced ICAM-1 and HLA-DR antigen expression on the surface of cultured human umbilical vein endothelial cells, assessed by flow cytometry, and EC proliferation by counting cell numbers and [3H]thymidine incorporation assays. Nicotinamide dose-dependently inhibited the IFN-gamma-induced ICAM-1 and HLA-DR antigen expression, but not HLA-A, B, C antigen expression on cultured EC. Furthermore, nicotinamide significantly inhibited endothelial cell proliferation, as assessed by [3H]thymidine incorporation assay. Our findings suggest that nicotinamide may suppress mononuclear cell infiltration, antigen presentation and angiogenesis in the lesions of autoimmune disorders by reducing both IFN gamma-induced ICAM-1 and HLA-DR antigen expression on EC, and EC proliferation. Therefore, nicotinamide can be used for the treatment and prevention of the development of autoimmune disorders.

Antigens, CD

Role of magnetic resonance imaging in thyroid-associated ophthalmopathy: its predictive value for therapeutic outcome of immunosuppressive therapy.

To investigate the efficacy of magnetic resonance imaging (MRI) in the assessment of thyroid-associated ophthalmopathy (TAO), 51 patients with TAO were evaluated by ophthalmologic examinations and MRI at 0.5 T. Thickness of extraocular muscles (EM) was measured by T1-weighted image. Signal intensities of EM and orbital connective tissue (OCT) were measured by short inversion time inversion recovery (STIR) image and expressed as a ratio by comparison to the signal intensity of cerebral substantia alba (SI, signal intensity ratio). Significant enlargement of one or more EM was observed in 86% of patients with TAO, and SI of EM (2.15 +/- 0.63, mean +/- SD) was significantly increased compared with control values (n = 16; 1.35 +/- 0.33; t test, p < 0.01). SI of OCT tended to be greater than that in the control group, although the difference was not significant. There was a significant positive correlation between thickness of EM and severity of ophthalmopathy, assessed as an ophthalmopathy index (p < 0.05). SI of neither EM nor OCT correlated with the severity of the eye disease. To investigate whether MRI findings could predict the outcome of methylprednisolone pulse therapy, we studied 23 patients with TAO who received this treatment. SI of EM and OCT in the 12 patients giving favorable responses were significantly greater than those in the 11 patients without good response (t test, p < 0.01). On the other hand, the thickness of eye muscles did not correlate with the outcome of treatment except for that of medial rectus muscle. There was a significant correlation between SI of EM and that of OCT (r = 0.78, p < 0.01), suggesting possible similar pathologic processes in these tissues in TAO.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Nicotinamide and 3-aminobenzamide inhibit recombinant human interferon-gamma-induced HLA-DR antigen expression, but not HLA-A, B, C antigen expression, on cultured human thyroid cells.

OBJECTIVE: We wished to investigate the effects of nicotinamide and 3-aminobenzamide, well known as inhibitors of poly(ADP ribose) synthetase, on interferon-gamma-induced HLA-DR antigen expression using cultured human thyroid cells from patients with Graves' disease. DESIGN AND MEASUREMENTS: Cultured thyroid cells were incubated for 3 days with 10-400 U/ml of interferon gamma in the presence of nicotinamide, 3-aminobenzamide, superoxide dismutase or catalase. The surface expression of HLA-DR and HLA-A, B, C antigen was measured by flow cytometry. RESULTS: Nicotinamide and 3-aminobenzamide dose-dependently inhibited the induction of HLA-DR antigen expression by interferon gamma, but not HLA-A, B, C antigen expression on cultured thyroid cells. Neither catalase nor superoxide dismutase, which are free-radical scavengers, inhibited the expression of HLA antigens on thyroid cells. CONCLUSIONS: Our data suggest that inhibitors of poly(ADP ribose) synthetase may have differential effects on interferon-gamma-induced HLA-DR and HLA-A, B, C antigen expression, and suppress the autoimmune reactions associated with autoimmune thyroid disorders via the reduction of HLA-DR antigen expression on thyroid cells. The mechanism of the suppression of HLA-DR antigen expression is unlikely to be due to the free radical scavenging.

Benzamides

Rosette formation of impacted molar teeth in mucopolysaccharidoses and related disorders.

The radiographic features of the jaws in the mucopolysaccharidoses and related disorders (MPS) have been reviewed and three further cases are reported here, with particular reference to a novel dental anomaly, not previously described in detail, in two of them. The dental changes appear to be fully developed by the third decade and are characterized by bilateral multiple impacted molar teeth, which conglomerate in a single follicle to form a characteristic rosette of teeth. Rosetting was present only in relatively mature cases of MPS. However, it was also seen in the fourth patient, where we could not detect any other abnormal clinical or radiographic features. We therefore propose that since multiple rosetting of molar teeth can also occur in an isolated form, it is only suggestive of MPS.

Adolescent

Anti-eye muscle antibodies and hypothyroid Graves' disease: a case report.

We report the case of a 70-year-old man who developed hypothyroidism associated with TSH receptor antibodies and severe ophthalmopathy during lithium therapy. He had received lithium therapy for more than 20 years for manic depression, when ophthalmopathy (class VI of the American Thyroid Association classification) and mild hypothyroidism developed. Orbital magnetic resonance imaging indicated marked enlargement of the superior, medial and inferior rectus muscles in the left eye. He had anti-eye muscle antibodies in his serum, detected by Western blotting and quantified by chromatoscanning, as well as anti-TSH receptor antibodies. He was treated with supplementation of levothyroxine and four cycles of methylprednisolone pulse therapy. After the pulse therapy, both anti-eye muscle antibodies and anti-TSH receptor antibodies decreased and disappeared in parallel with the improvement in eye symptoms and signs. These observations suggest the importance of anti-eye muscle antibodies as clinical markers in the development of thyroid-associated ophthalmopathy.

Aged

Significance of anti-eye muscle antibody in patients with thyroid-associated ophthalmopathy by quantitative western blot.

To investigate the prevalence of antibody against rat eye muscle membrane antigen, as determined from SDS-polyacrylamide gel electrophoresis and western blotting, in sera from patients with thyroid-associated ophthalmopathy (TAO), we quantitatively analyzed the binding activity with a rat eye muscle membrane 64 kDa protein using chromato-scanner. Eye muscle antibody activity was expressed as ratio of density of the 64 kDa band to that at 66 kDa found with all normal sera and phosphate buffered saline. The mean (+/- SD) eye muscle antibody activity was 2.7 +/- 2.7 in TAO (P < 0.01 v.s. normal), 1.5 +/- 1.7 in Graves' disease without evident eye disease, 1.6 +/- 2.5 in Hashimoto's thyroiditis and 0.45 +/- 0.26 in normal subjects. A positive band at 64 kDa was found in 71% of patients with TAO, 36% of those of Graves' disease without evident eye disease and in 35% of patients with Hashimoto's thyroiditis without eye disease. The prevalence of this antibody activity tended to correlate to the severity of ophthalmopathy. Furthermore, the level of eye muscle antibody activity decreased in parallel with the improvement of eye signs in two patients. Sera reactive with rat eye muscle membrane 64 kDa protein reacted also with a human eye muscle membrane 64 kDa protein but not with human thyroid, liver, spleen or pancreas membrane preparations. In conclusion, antibody to rat eye muscle membrane 64 kDa protein is present in TAO and may be a useful clinical marker of ophthalmopathy.

Adolescent

[A clinical and ultrastructural study of Fechtner syndrome in two Japanese families].

This is a report of Fechtner syndrome in two Japanese families. Six members of family I and three members of family II were studied. All but one had macrothrombocytopenia and leukocyte inclusion bodies, four had deafness, four had persistent proteinuria and none had cataracts. Under a diagnosis of ITP, two of them had splenectomy which resulted in no response. History revealed, other family members with deafness and/or nephritis were confirmed in both families. Ultrastructural studies of leukocytes showed oval inclusion bodies with unclear borders containing many fine ribosome like granules and randomly scattered filaments. Ultrastructural studies of macrothrombocytes were unremarkable except for a well-developed open canalicular system. More than half of megakaryocytes had uneven basophilic speckles in the cytoplasm, which were positive for Unna-Pappenheim staining. Ultrastructurally, widening of demarcating systems and remaining ribosomes were noted in the cytoplasma of mature megakaryocytes.

Deafness

[Endoscopic closure of the postoperative bronchopleural fistula].

A case of successful endoscopic closure of a bronchopleural fistula with fibrin glue was reported. Fifty-eight-year-old man underwent right lower lobectomy for lung carcinoma. On the 21st postoperative day, he suffered from high fever and diagnosed as right side pyothorax. Then tube thoracotomy was done under UCG-guide. As a fistula in the right lower bronchial stump was found tiny by BFS, we tried to close the fistula bronchoscopically with fibrin glue. The fibrin glue was injected into the fistula via the ERCP tube, which was passed through the bronchoscope. This procedure was performed twice for two weeks interval. The fistula was completely closed about a month after the trial. This method is useful to close postoperative small bronchopleural fistula without surgical intervention.

Bronchial Fistula

Lymphocytic hypophysitis and pulmonary sarcoidosis. Report of a case.

Lymphocytic hypophysitis is one of the causes of hypopituitarism in the postpartum period. Some of these patients have been reported to have other organ-specific autoimmune diseases, and the disease is considered to be autoimmune in nature. The authors describe a unique case of lymphocytic hypophysitis in a young woman. She had hemianopia that developed three days after delivery. Computed tomography scans revealed an intrasellar mass lesion. Secretions of adrenocorticotropic hormone and growth hormone were decreased. Although no organ-specific autoantibodies were detected in her serum, OKT4-positive helper T lymphocytes were increased in peripheral blood. Pituitary biopsy at craniotomy showed typical features of lymphocytic hypophysitis. Pulmonary and eye sarcoidosis developed 11 months after the delivery. This is, to the authors' knowledge, the first case of lymphocytic hypophysitis associated with sarcoidosis in other organs.

Adult

Comparison of body temperature rhythms between healthy elderly and healthy young adults.

The fact that the elderly are usually aware of early sleep onset and early morning awakening shows that the phase of sleep-wake rhythms in the elderly is more advanced than that in young adults. Since it has been suggested that human sleep onset, morning awakening, sleep period and depth of sleep are highly influenced by body temperature rhythms, rectal temperature rhythms were analyzed in 7 healthy elderly and 7 healthy young adults under the condition with time cue. Although a significant 24-hour period was found in the rhythms for all subjects, the phase of the rhythms in the elderly was more advanced than in the young adults. Moreover, a significant inverse correlation was observed between age and acrophase time in the elderly.

Adolescent

Selective hypoaldosteronism in a patient with Sjögren's syndrome: insensitivity to angiotensin II.

A 51-year-old Japanese woman with hypokalemia due to distal renal tubular acidosis associated with Sjögren's syndrome exhibited a decreased plasma aldosterone level despite elevated plasma renin activity. Our studies revealed selective hypoaldosteronism with normal adrenoglucocorticoid function. In the presence of a low level of serum potassium (3.6 mEq/l), plasma levels of deoxycorticosterone and corticosterone were normal, while plasma aldosterone was very low. The levels of these three mineralocorticoids showed only minor changes during infusion of angiotensin II. Furosemide administration under almost the same level of serum potassium (3.7 mEq/l) resulted in only a slight increase of plasma aldosterone. Since hypokalemia might possibly suppress the synthesis of aldosterone in the zona glomerulosa, angiotensin II was also infused under a normal level of potassium (4.3 mEq/l). However, angiotensin II also failed to stimulate any secretion of aldosterone, despite a progressive rise in blood pressure and sufficient suppression of plasma renin activity. On the other hand, rapid ACTH administration in the presence of 4.4 mEq/l of serum potassium increased both plasma aldosterone and cortisol. These results suggest that adrenal insensitivity to angiotensin II was the cause of the selective hypoaldosteronism in our patient, possibly due to a dysfunction of adrenal angiotensin II receptors, a disorder of postreceptors or both.

Acidosis, Renal Tubular

Glucose-depletion suppresses synaptic transmissions in rat dorsolateral septal nucleus.

Removal of extracellular glucose hyperpolarized the post-synaptic membrane of dorsolateral septal nucleus (DLSN) neurons. Glucose-depletion suppressed the excitatory postsynaptic potential (EPSP) and the late hyperpolarizing potential (LHP) without affecting the responses induced by glutamate or baclofen. Glibenclamide did not antagonize the effects produced by glucose-depletion. These results suggest that glucose is necessary to maintain the membrane excitability and transmitter-release in rat DLSN.

Animals

Seasonal effects on fetal selection related to AB0 blood groups of mother and child.

An association of AB0 blood groups and month of birth was examined in two groups, students and newborns in Tokyo. Among 4919 students born mainly in the 1960s, an apparent seasonal variation was shown in births of blood group B students. Among 3592 newborns at an obstetric clinic in the 1980s seasonal variation was also observed in all four blood groups. The ratio of 0 group to A group newborns (0/A ratio) from 0 mothers was lower than that from A mothers among the 0 and A pairs contrary to the expected effects of 0-A incompatibility. The 0/A ratio was apparently different by season and the 0/A ratio from 0 mothers was significantly lower than that from A mothers among those born during August-January. It is assumed that an association of birth season with AB0 blood group may be caused by some seasonally and secularly changing environmental "infertility factors" such as infectious microorganism which may have some common components with a particular blood group substance respectively and induce a loss of embryos selectively at a particular season.

ABO Blood-Group System

[Surgical repair of postinfarction cardiac rupture in three cases].

Operative managements and results of postinfarction left ventricular (LV) rupture in 2 patients and right atrial (RA) rupture in one patient are reviewed. Two patients showed both subacute onset of LV rupture in association with cardiac tamponade. The site of infarction was inferior wall in one and anterior wall in the other. Both patients underwent infarctectomy with closure of the defect using a Dacron felt patch. Endocardial site of the Dacron patches were covered with own pericardium to avoid bleeding from the patch and postoperative complication of endocardial clot formation. The case with extended inferior wall infarction was succumbed to cardiac failure and acute renal failure at the twelfth postoperative day. The other case was uneventful postoperatively and shows excellent long-term result. Left ventriculography and coronary angiographic studies were carried out 3 months after the surgery. It demonstrated 43% of LVEF. Multiple stenotic lesions were also noted in left coronary artery. The third patient was rupture of the RA in association with cardiac tamponade. Direct suture closure of the rupture was carried out under extracorporeal circulatory support. Patient tolerated the procedure well. Postoperatively, he suffered from exacerbation of renal insufficiency necessitating hemodialysis for a month. He discharged from hospital and now in the good condition. Postoperative RI study and coronary angiography demonstrated no compatible finding of right atrial infarction. However, pathological specimen revealed definite diagnosis of the infarction at the RA appendage.

Aged