[Endocrinological approach to symptoms and diagnosis of goiter].
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Biomedical subjects
Publications and source records attributed to T Mitsuma.
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Geometrical analysis of highly-purified and low-density adult rat dorsal root ganglion (DRG) neuron culture proved that laminin enhanced the total neurite length and the maximal extension of neurites, but did not significantly increase the neurite branching nor soma size particularly after 4 days of culture. Survival rates of adult DRG neurons were not affected by laminin. These results suggest that laminin is a potent modulator of neurite geometry in adult rat DRG neurons, which promotes neurite elongation rather than neurite branching.
The effects of water-immersion-induced stress and intraperitoneal (i.p.) administration of selected neuropeptides on the levels of thyrotropin-releasing hormone (TRH) and prostaglandin E2 (PGE2) were studied in the rat stomach. Water-immersion caused a significant decrease immunoreactive-TRH (ir-TRH) concentrations in the stomach, and a significant increase in ir-TRH concentrations in the gastric juice. The concentrations of PGE2 were significantly increased at 0.5-4 hrs, and significantly decreased at 6-8 hrs after water-immersion. In the experiment of i.p. administration of selected neuropeptides, the level of ir-TRH in the stomach was significantly decreased after VIP injection, whereas it was significantly increased after beta-endorphin injection. The concentration of PGE2 was significantly decreased in the stomach after i.p. administration of TRH and VIP. However, it did not change after beta-endorphin injection. These results indicate that some neuropeptides may participate in regulating the endogenous level of PGE2 and that these interrelations between neuropeptides and PGE2 may be important as ulcerogenic factors in stress ulcers induced by water-immersion in the rat.
The effects of hypophysectomy on pro-thyrotropin-releasing hormone (pro-TRH) and TRH concentrations in the rat hypothalamus, cerebrum, cerebellum and brain stem, stomach and eye were studied. The hypophysectomy was performed via ear route and the rats were used for experiments at seven days after the operation. The hypophysectomized rats were administered T4 (500 micrograms/kg), T3 (100 micrograms/kg), TRH (1.0 mg/kg), or bovine TSH (1.25 IU/kg) was injected ip, and five rats in each subgroup were decapitated at four hours after the injection. Pro-TRH, TRH, TSH and thyroid hormone were measured by their radioimmunoassays. Immunoreactive pro-TRH (ir-pro-TRH) concentrations in the hypothalamus increased significantly after hypophysectomy, while its concentrations in the other tissues showed no changes. The immunoreactive TRH (ir-TRH) concentrations in the hypothalamus decreased significantly after hypophysectomy, but its concentrations did not change in the other tissues. In the hypophysectomized rats, ir-pro-TRH concentrations in the hypothalamus decreased significantly after T4 or T3 injection and tended to decrease after TRH or TSH injection. The ir-TRH concentrations in the hypothalamus increased significantly after T4, T3, TSH or TRH injection in the hypophysectomized rats. However, ir-pro-TRH and ir-TRH concentrations in the other tissues did not change after these hormone injections. The findings suggest that hypophysectomy stimulates TRH synthesis and release in the hypothalamus, and that pro-TRH synthesis in the tissues except the hypothalamus may not be regulated with thyroid hormone.
A 65-year-old house-wife developed dirty erythematous rash on her face in April, 1989. Almost simultaneously, she complained of muscle soreness and weakness on both lower extremities. Pathological findings of the skin biopsy at that time was consistent with those of sarcoidosis with moderate inflammatory cell infiltration. In December, 1989, when she was admitted to our hospital, her lower extremities were paretic with marked spasticity, and mild bladder dysfunction was noted. HTLV-I antibody titers in serum and cerebrospinal fluid were significantly elevated. Biopsied limb skeletal muscle revealed the findings of the sarcoid myopathy with small inflammatory cell infiltration in endomysium. HLA haplotypes showed A24, B7, BW61, CW7, CW8, DR1 and DR4 which show relatively common types of those in HAM. Corticosteroid treatments including the methylprednisolone pulse therapy healed the skin lesion, but did not improve her neurological signs. Paraplegia and urinary disturbance were progressive. It is concluded that the inflammatory sarcoid myopathy with HAM in this patient may be caused by a common abnormal immunological background.
We have reported two cases of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) associated with Graves' disease. Case 1: a 45-year-old woman noticed a diffuse goiter, palpitation and emaciation in 1977. Laboratory studies confirmed that she had Graves' disease, and she was treated with antithyroid drug. In 1986, when the hyperthyroidism was subsided, she showed progressive symmetrical weakness and numbness in her limbs, and she was almost in tetraplegia at 1987. Markedly slowed motor and sensory nerve conductions and elevated CSF proteins as well as clinical manifestations confirmed the diagnosis of CIDP. Following corticosteroid-pulse therapy and plasmapheresis resulted in good recovery in both motor and sensory impairment, though two-times of relapses were observed. Case 2: a 33-year-old man first noticed weakness in his legs in 1977, motor and sensory disturbances progressed for 12 years. Slowed nerve conduction, high CSF proteins and two-times of relapses in early phase indicated that the CIDP was the diagnosis. In 1989 he complained general fatigue, hyperhidrosis and body-weight loss. The serum thyroid hormone levels were high, and other laboratory studies confirmed the presence of Graves' disease. The cases with both CIDP and Graves' disease has rarely been reported. The background mechanism of this association is not well understood, but the susceptibility to CIDP and Graves' disease may be related to the HLA antigens and immunoglobulin Gm allotypes of which are the genes linked to the major histocompatibility complex and controlling immune responses. The present two cases commonly shared several HLA-DR antigens, but their significance should be confirmed by examining many cases.
The effect of local administration of calcitonin gene-related peptide (CGRP) on sweating activity was evaluated on normal human volunteers. CGRP and methacholine chloride (MCH) was dissolved in 0.1 ml of 0.9% NaCl solution to a specified concentration, and was injected intradermally at the center of a 1.3 cm2 forearm test area. The sweat rate was recorded continuously by capacitance hygrometry in a relatively cool environment (Ta, 23 degrees C). CGRP did not elicit any sweat secretion when administrated by alone, but significantly increased the sweat rate when it was administrated with MCH. The maximum enhancement of MCH-induced sweating by CGRP was observed at a concentration of 10(-5) g/ml of CGRP. There was clear dose-dependent relationship between the dose of CGRP and its enhancement. Recently, CGRP-like immunoreactivity is demonstrated to be present in cholinergic nerve terminals around the human sweat glands. These observations have strongly suggested that CGRP enhances the cholinergic sweating activity. Although the underlying mechanism is still obscure, CGRP may enhance the sweating as a consequence of vasodilation which has been known to be a major activity of CGRP. As for the evaluation of human sweat gland function, CGRP-induced peptidergic regulation should be considered as well as cholinergic regulation.
We evaluated immunological tests for autoimmune thyroid diseases. Although both humoral and cellular immunity are correlated to the onset and pathophysiological progression of these diseases, the major tests employed in daily clinic belong to the former. We measured the anti-TSH receptor antibody (TRAb, TBII), circulating immune complex (CIC), thyroid growth stimulating immunoglobulin (TGSI) and interleukin-2 (IL2) levels in patients with Graves' disease (GD) and chronic thyroiditis (CT). The normal range of TRAb in 190 healthy controls was from -10.9 to +10.3% calculated from the mean +/- 2SD. Sixty eight out of 78 untreated cases of GD (87.2%) showed a higher TRAb than the upper normal level (positive), 92 out of 131 cases of GD under treatment (70.2%) were positive and only 5 out of 57 cases of treated GD (8.8%) were positive. Three neonates out of 12 GD mothers had a positive TRAb and one of them developed neonatal GD. Nine out of the 45 CT (20%) had positive TRAb, but about half were euthyroid and goitrous. In untreated GD, CIC was distributed widely from the normal range to high levels. CIC showed a significantly negative correlation with TRAb. TGSI correlated with goiter size and CIC in GD revealed autologous inhibition on TGSI. Three cases showed markedly decreased levels of TRAb which was found to be due to anti-TSH antibodies. Production of IL2 in GD was impaired, but it was improved by treatment of GD.(ABSTRACT TRUNCATED AT 250 WORDS)
Nineteen cases of amaurosis fugax (AF) were analyzed in clinical study undertaken to address the problem of its pathogenetic mechanism. This series comprised 10 male and 9 female with an age range of 26-77 years. In 8 cases, AF was the only clinical manifestation, while in the other 11, AF was accompanied by hemispheric TIA. The attack lasted for a few to 15 minutes on most occasions, occurring on the left side in 7 cases and on the right in 12 cases. On the basis of cerebral angiographic findings and findings on transcranial Doppler blood velocity measurements (TCD), these cases were classified into 4 types of different etiology, i.e. (Group A) micro-embolus via internal carotid artery origin--7 cases (5 with stenosis at the level of siphon, 2 with stenosis of the ophthalmic artery); on TCD the direction of blood flow in ophthalmic artery was normal (forward flow) in 5 cases and antiplatelet therapy proved effective in 4 cases, (Group B) micro-embolus derived via the external carotid artery--5 cases (3 with complete occlusion of internal carotid artery at its origin, 2 with severe stenosis there of); TCD showed blood flow in the ophthalmic artery to be in a direction opposite to the normal (away flow) in 3 cases and 3 cases responded favorably to antiplatelet therapy, (Group C) cerebral hemodynamic crisis--3 cases (severe cardiac hypofunction following myocardial infarction, orthostatic hypotension, and elongation of internal carotid artery), and (Group D) unknown etiology--4 cases; cerebral angiography revealed no abnormalities, suggesting involvement of other factors than cerebrovascular agents.(ABSTRACT TRUNCATED AT 250 WORDS)
Histopathology of the somatic motor efferents of three cases with pseudopolyneuritic from of amyotrophic lateral sclerosis (ALS) was analyzed, and the results were correlated with the clinical symptoms. The population of myelinated fibers in the lateral corticospinal tract at the thoracic segment, and in the fourth ventral roots, and motor neurons in the fourth ventral horns were morphometrically quantified. The patients were two males and one female ranging in age from 43 to 67 years, and showed a clinical course of 1.8 to 9.5 years. All three cases did not show any pyramidal sign nor spasticity but showed an extensive leg involvement, particularly the distally accentuated muscular weakness with depressed deep tendon reflexes. The clinical manifestations were consistent with the pseudopolyneuritic form of ALS. Fiber size profile of the myelinated fibers in the lateral corticospinal tracts at T7 segments and L4 lumbar ventral roots were estimated on the epon-embedded transverse sections as previously described (Sobue et al, 1981). Number and size distribution of anterior horn cells in the L4 segments were measured on 300-500 consecutive 10 microns-thick paraffin sections stained with Klüver-Barrera technique, using a TGZ-3 particle size analyzer (Zeiss). The location of the remained anterior horn cells was also quantitatively estimated. Three cases with common form of ALS and three control cases were analyzed in the same manner. The large myelinated fibers in the lateral corticospinal tract were extensively and predominantly depleted in all three cases. The small myelinated fibers were also depopulated but in lesser degree. The mode of these myelinated fiber loss was almost compatible with those in common form of ALS.(ABSTRACT TRUNCATED AT 250 WORDS)
Nerve growth factor (NGF) is a well-established trophic factor of sympathetic and sensory neurons during development. NGF is, however, little known to be required for the maintenance or regulation of differentiated phenotypes of matured peripheral neurons. Since trophic factors, including NGF, are currently known to be secreted by non-neuronal cells, like Schwann cells and fibroblasts, a highly pure-neuron culture is required to assess the direct action of trophic factors on neurons. We have developed a single-neuron culture from neonatal and adult rat dorsal root ganglia in serum-free conditions, and estimated the primary effect of NGF on the morphological geometry of sensory neurons. We found that NGF promoted the neurite length of neonatal sensory neurons, rather than promoting arborization (branching of neurites), while in adult matured neurons NGF significantly enhanced neurite arborizations, rather than the maximal neurite extension, distance from the cell soma to the maximum margin of the territory of neurite extension. Total neurite length, the summed length of all neurites per neuron was significantly increased by NGF in both neonatal and adult neurons. NGF also increased the size of neuronal soma independent of neuronal maturation. Neonatal sensory neurons tended to die in 1 week despite the presence of NGF. In contrast, some adult sensory neurons were alive for more than 2 weeks in the absence of NGF. These results indicate that NGF more than simply accelerates a pre-existing developmental program in the matured stage, and that the promotion of neurite arborization by NGF in adult sensory neurons suggests that NGF may have some role in peripheral nerve regeneration via promotion of axonal sprouting.
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Lower motor neurons of the spinal cord of patients with amyotrophic lateral sclerosis (ALS), Werdnig-Hoffmann's disease (WH), X-linked recessive bulbospinal neuronopathy (X-BSNP) and multiple system atrophy (MSA), all of which were known to involve the lower motor neurons, were immunohistochemically examined by using a monoclonal antibody (Ta-51) specific to phosphorylated epitopes of high molecular weight subunits of neurofilaments. The incidence of Ta-51-positive neurons was significantly increased in ALS, WH and MSA, but not in X-BSNP. Ta-51-positive neurons showed a wide variety of morphological appearances, including neurons with normal appearance, central chromatolysis, simple atrophy and neurons containing massive neurofilamentous accumulation. In aged-control cases, similar Ta-51-positive neurons were observed, although to a much lesser extent. In ALS, spheroids and globules, which were strongly positive for Ta-51, were also significantly increased. Ta-51-positive motor neurons, spheroids and globules appeared in proportional to the number of remaining large motor neurons in ALS.
The effects of histamine and its related compounds on the concentrations of immunoreactive thyrotropin-releasing hormone (ir-TRH) in the stomach, gastric juice and hypothalamus in rats were studied. Histamine, ranitidine or ethanolamine was injected intraperitoneally, and the rats were decapitated at various times after the injection. Ir-TRH concentrations in the stomach, gastric juice and hypothalamus were measured by a radioimmunoassay. Ir-TRH concentrations in the stomach decreased significantly after histamine injection and increased significantly after ranitidine injection in a dose-dependent manner, but did not change with ethanolamine. Ir-TRH concentrations in the gastric juice increased in a dose-dependent manner, peaking at 30 min after histamine injection, and its effect was blocked with ranitidine. Ir-TRH concentrations in the hypothalamus elevated significantly after histamine injection and reduced significantly after ranitidine injection, but did not change with ethanolamine. The effects of histamine on ir-TRH concentrations in the stomach and hypothalamus were significantly blocked with ranitidine, but not with ethanolamine. These findings suggest that histamine stimulates ir-TRH release from the stomach and inhibits ir-TRH release from the hypothalamus, and that these effects of histamine on ir-TRH release are mediated via an H2-receptor.
Concentrations of pro-thyrotropin-releasing hormone (pro-TRH) were studied in the brain of the Weaver ataxic mouse, the Purkinje cell degenerative mouse (pcd-ataxic mouse), the Staggerer ataxic mouse and the C3H mouse. The brain tissue was dissected into 7 parts, e.g., hypothalamus, cerebrum, thalamus, striatum, brain stem, cerebellum and cervical spinal cord. Pro-TRH concentrations in each part of the brain were measured by radioimmunoassay. Pro-TRH concentrations in the brain of Weaver ataxic mice, pcd-ataxic mice and Staggerer ataxic mice were significantly higher in the thalamus, brain stem, cerebellum and cervical spinal cord. Pro-TRH concentrations in the hypothalamus, striatum and cerebrum of ataxic mice did not differ from those of controls. The elution profile of acetic acid extracted cerebellum of ataxic mice on Sephadex G-50 was identical to that of synthetic pro-TRH. These findings suggest that changes in pro-TRH concentrations in the brain may play a pathophysiological role in ataxic mice.
The effect of bifemelane hydrochloride on plasma beta-endorphin-like immunoreactivity (beta-En-LI) levels in rats was studied. Bifemelane hydrochloride (25 mg/kg) was injected i.p., and the animals were decapitated at various times after the administration. The plasma beta-En-LI levels were measured by radioimmunoassay. The effect of bifemelane hydrochloride on beta-En-LI release from the anterior pituitary was also investigated by means of an in vitro experiment. The beta-En-LI content in the hypothalamus and pituitary gland did not change significantly after bifemelane hydrochloride injection. The plasma beta-En-LI levels decreased significantly in a dose-related manner with a nadir at 40 min after the injection. The beta-En-LI release in vitro from the anterior pituitary was inhibited with the addition of bifemelane hydrochloride. The findings suggest that bifemelane hydrochloride acts on the anterior pituitary to inhibit beta-En-LI release.
We have developed a sensitive, reproducible and specific radioimmunoassay for human interleukin-2. Using 125I-labeled interleukin-2 and polyclonal rabbit antisera raised against recombinant human interleukin-2, a competitive inhibition assay was described which could detect 1 U/ml of human interleukin-2. Substances such as interleukin-1 alpha, interferon beta, nerve growth factor, tissue necrotizing factor, various hormones, peptides and lectins did not affect the assay. Interleukin-2 was measured in supernatants of culture media of stimulated human blood mononuclear cells. Kinetics of interleukin-2 production in seven normal lymphocytes revealed that in both PHA- and Con A-stimulations, the peak levels of interleukin-2 were seen at the end of 72 hours (113.9 +/- 54.4 U/ml, 111.6 +/- 37.3 U/ml, respectively) and then declined. Interleukin-2 levels in PHA- and Con A-stimulations of untreated Graves' disease were significantly lower (14.5 +/- 15.5 U/ml, 12.3 +/- 12.7 U/ml, respectively) than normal controls. However, the improvement of decreased interleukin-2 production in methimazole-treated patients with Graves' disease was observed (38.2 +/- 28.1 U/ml, 48.0 +/- 35.6 U/ml, respectively). The present study demonstrates the usefulness of quantitating human interleukin-2 produced by human blood mononuclear cells and that there exists an impaired production of interleukin-2 in Graves' disease.