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Biomedical subjects

T Mitsuma

Publications and source records attributed to T Mitsuma.

At least 145 records · Page 8Linked to original sources

[The corticospinal tract lesion of amyotrophic lateral sclerosis--magnetic resonance imaging of the spinal cord].

Magnetic resonance imaging by gradient echo method demonstrated lesions of the lateral corticospinal tract at cervical cord levels in three ALS patients. Patient 1 was a 43-year-old woman with common form of ALS. She developed right-side predominant pyramidal signs, and right-side predominant prolongation of central motor conduction time. MRI showed hypersignal intensity areas in the dorsal region of the lateral column at the 4th and 5th cervical segments with right-side predominancy. Patient 2 was a 65-year-old man with pseudopolyneurtic form of ALS, who showed lower motor neuron signs without a pyramidal sign. MRI of the 3rd and 4th cervical cord segments demonstrated bilateral hypersignal intensity areas in the dorsal part of the lateral column. Patient 3 was a 62-year-old man with common form of ALS, who showed marked bilateral pyramidal signs with Babinski's sign. MRI of the 5th cervical spinal cord segment demonstrated bilateral hypersignal intensity areas in the dorsolateral column. Thus obtained MR images of the spinal cord corresponded well to the postmortem-confirmed degeneration of the spinal corticospinal tract. MRI of the spinal cord performed by gradient echo method would provide additional information on the upper motor neuron involvement in ALS.

Adult↗

Effects of hypophysectomy on TRH and its related peptides concentrations in various rat organs.

The effects of hypophysectomy on thyrotropin releasing hormone (TRH), TRH-glycine (TRH-Gly) and pre-pro-TRH (178-199) concentrations in the rat hypothalamus, cerebrum, cerebellum, brain stem, stomach and retina were studied 7 days after the operation. The hypophysectomized rats were administered a single i.p. injection of T4 (500 micrograms/kg), T3 (100 micrograms/kg) or bovine TSH (1.25 IU/kg), and 5 rats of each subgroup were decapitated at 4 hours later. After hypophysectomy, TRH-Gly and pre-pro-TRH (178-199) concentrations in the hypothalamus increased significantly and TRH concentrations decreased after hypophysectomy. After the injection of T4, T3, TRH or TSH TRH-Gly and pre-pro-TRH (178-199) concentration in the hypothalamus of hypophysectomized rats decreased significantly, while that of TRH significantly increased. No changes in TRH, TRH-Gly and pre-pro-TRH (178-199) concentration in other tissues were observed after hypophysectomy or hormone treatment. The findings suggest that hypophysectomy stimulated TRH synthesis and release in the hypothalamus, that TRH, TSH, T3 and T4 regulate hypothalamic TRH levels, and that pro-TRH synthesis in the tissues except the hypothalamus may not be regulated by thyroid hormone.

Animals↗

[Chronological changes in MR imaging of inferior olivary pseudohypertrophy--report of two cases].

Olivary pseudohypertrophy (OH) and its chronological change was examined by MR images in two patients with brainstem vascular disease. Patient 1 was a 63-year-old woman who developed an infarction in the red nuclei associated with "top of the basilar" syndrome. Two months later, she showed 2-4 c/s rhythmic myoclonus (rubral tremor) involving four extremities. Palatal myoclonus was absent. MR images of the inferior olives did not demonstrate a significant lesion in 10 days after the onset, but showed OH in 6 months, and then their size attained a maximum in 10 months after. On T2-weighted (T2) images and proton-density-weighted (PD) images obtained at 20 and 24 months, OH gradually became irregular but discrete in their intensity, and the intensity had also decreased to some extent. Rhythmic myoclonus had subsided to some extent after 20 to 24 months. Patient 2 was a 62-year-old woman who had a small hemorrhage in the pontine tegmentum. She developed 2.5 c/s vertical ocular myoclonus without palatal myoclonus two months after the onset. MR images showed OH in 6 and 8 months after the onset. On T2 and PD images obtained at 20 months, the image of OH gradually developed to become irregular in intensity and slightly atrophic in size. The ocular myoclonus somewhat reduced in their intensity 12 months after the onset. These serial changes in MR images were considered to correspond to the chronological changes of the pathology of OH. Appearance and subsidence of the myoclonic movement was also considered to correlate to the sequential changes of MR images of OH.

Cerebrovascular Disorders↗

[Hemodynamic TIA associated with severe anemia--a case report].

A 62-year-old man developed recurrent TIAs presenting as mild unconsciousness, dysarthria and weakness of the right upper extremity lasting for 15 to 20 minutes. He was found to have severe iron deficiency anemia (hemoglobin: 5.5-5.9g/dl; hematocrit: 18.4-19.5%) which insidiously developed through the chronic bleeding from the gastric ulcer. He had slight hypertension (184/86mmHg), but no orthostatic hypotension. DSA and MR angiography showed severe stenosis at the origin of the bilateral internal carotid arteries and of the left vertebral artery. There was also hypoplasia of the right vertebral artery. Blood circulation detected by 123I-IMP-SPECT was markedly decreased in the whole brain and in the right hemisphere of the cerebellum. TIA was, however, completely disappeared following to the recovery of anemia. The present case suggested that the presence of severe anemia accelerated the occurrence of hemodynamic TIA (regional cerebral anemic hypoxia), which is probably the consequence of the reduced oxygen-transporting capacity of the blood.

Aged↗

[Skin sympathetic nerve activity in amyotrophic lateral sclerosis].

Skin sympathetic nerve activity (SSNA) was microneurographically analyzed in five patients with amyotrophic lateral sclerosis (ALS) (four men, one woman; age ranges between 36 and 68 years) and 16 age- and sex-matched controls. The duration of illness after the onset was ranged between 1 and 3 years. Three cases were the common form of ALS showing a moderate to severe involvement of the upper extremities and mild degree of bulbar signs. Two were the pseudopolyneuritic form with lower motor neuron sign predominant in the legs. All these patients could walk by alone and did not show any respiratory distress. SSNA was recorded directly by inserting a tungsten microelectrode into the tibial nerve at the popliteal fossa as described before. The sweat rate and skin blood flow on the area innervated by the tibial nerve were also monitored. Resting activity of the SSNA (bursts/minute) was significantly higher (p < 0.05) in patients with ALS as compared with the controls. The rate of increase in SSNA under the load of mental arithmetic, tone, electric stimulation of the median nerve and immersion of the hand into cold water were only slightly higher in ALS. The rate of increase in SSNA response by these stimuli against the basal SSNA, however, was not significant. These results indicate that skin sympathetic nerve functions are hyperactive in ALS particularly in the basal resting level, though the underlying mechanism is unclear.

Adult↗

Gene expression of high- (p140trk) and low-affinity nerve growth factor receptor (LNGFR) in the adult and aged human peripheral nervous system.

Steady-state mRNA levels and immunoreactive proteins for high- (p140trk) and low-affinity nerve growth factor receptor (LNGFR) in the adult and aged human peripheral nervous system (PNS) were examined in autopsied material. trk mRNA expression was observed only in the sympathetic and dorsal root ganglia, while LNGFR mRNA was expressed widely through the PNS as well as non-neural tissues. Immunoreactive trk proto-oncogene product (p140trk) and LNGFR occurred in the perikarya of the subset of the sympathetic and dorsal root ganglion neurons, but only LNGFR immunoreactivity also occurred in the perineurium and the outer layer of the vessels. The spatial patterns of the trk and LNGFR gene expression in the adult human PNS were similar to those observed in the rat, mouse and chick, and their expression was well preserved in the aged.

Aged↗

Deregulated production of interleukin-4 (IL4) in autoimmune thyroid disease assayed with a new radioimmunoassay.

A sensitive, reproducible and specific radioimmunoassay for human interleukin-4 (IL4) has been developed. Using 125I-labeled IL4 and polyclonal rabbit antisera raised against recombinant human IL4, a competitive inhibition assay was developed which could detect 5 pg/ml of human IL4. Other interleukins, growth factors, hormones, peptides and lectins did not affect the assay. IL4 was measured in supernatants of culture media of stimulated human peripheral blood mononuclear cells (PBMC). Kinetics of IL4 production in PHA-stimulated PBMC from seven normal subjects revealed that the peak levels of IL4 were seen at 24 h and then declined. Peak IL4 levels in PHA stimulation of PBMC from untreated patients with autoimmune thyroid diseases (Graves' disease and chronic thyroiditis) were significantly higher than normal controls. However, after treatment, IL4 production decreased to normal. The present study demonstrates the usefulness of quantitating human IL4 produced by PBMC and that there exists a deregulated production of IL4 in autoimmune thyroid diseases.

Antibody Specificity↗

Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and low-affinity nerve growth factor receptor (LNGFR) mRNA levels in cultured rat Schwann cells; differential time- and dose-dependent regulation by cAMP.

Steady-state mRNA levels for NGF, BDNF, and NT-3, and their receptors, LNGFR, trk, trkB, and trkC, were examined in cultured rat Schwann cells. NGF, BDNF, and LNGFR mRNAs were expressed in control Schwann cells, but NT-3, trk, trkB and trkC mRNAs were not. As previously reported, when Schwann cells were treated with forskolin or 8-bromo-cAMP, NGF mRNA expression was enhanced, while BDNF and LNGFR mRNA levels were suppressed. The optimal concentration of forskolin for NGF mRNA enhancement and BDNF mRNA suppression was similar to that for LNGFR mRNA suppression, which coincided with the optimal concentration for Schwann cells to differentiate. However, the lag-time for forskolin-induces down-regulation of LNGFR mRNA was far greater than that for NGF mRNA increase and BDNF mRNA suppression.

8-Bromo Cyclic Adenosine Monophosphate↗

Chronic progressive sensory ataxic neuropathy: clinicopathological features of idiopathic and Sjögren's syndrome-associated cases.

Eleven patients with chronic progressive sensory ataxic neuropathy were examined clinicopathologically. Three cases were associated with primary Sjögren's syndrome (SS-SAN) and the others were considered to be idiopathic (ISAN). The major clinical symptom in both was loss of proprioceptive and kinesthetic sensation with some impairment of superficial sensation, with multifocal and asymmetrical distribution and progression. The truncal and trigeminal nerves were frequently involved. The motor system was substantially preserved. These somatic sensory and motor symptoms did not differ between ISAN and SS-SAN, but autonomic nervous system signs were more frequent in SS-SAN. Polyclonal elevations of serum IgG and/or IgA were seen in 8 patients. One autopsied case with ISAN combined with previous reports suggested that systemic T- and B-cell infiltration into the nervous tissues, as well as a wide variety of the visceral organs, may be a common finding in ISAN and SS-SAN, and could participate in the cause of this neuropathy and polyclonal hypergammaglobulinaemia.

Aged↗

The role of thyrotropin-releasing hormone (TRH) in the pathogenesis of water-immersion stress in rats--inhibition of TRH release from the stomach by atropine, ranitidine or omeprazole.

The role of thyrotropin-releasing hormone (TRH) in the development of gastric erosions and ulcers induced by water-immersion stress was studied. Intraperitoneally administered bethanechol induced a decrease in the gastric wall immunoreactive TRH (ir-TRH) concentrations and an increase in gastric juice ir-TRH concentrations in a dose-related manner, while atropine induced an increase in gastric wall ir-TRH concentrations and a decrease in gastric juice ir-TRH concentrations under non-stress condition. Intraperitoneally administered omeprazole did not influence gastric wall ir-TRH concentrations but elevated gastric pH. Water-immersion stress induced a decrease in gastric wall ir-TRH concentrations and an increase in gastric juice ir-TRH concentrations with a decrease in gastric pH prior to ulcer formation. Pretreatment with atropine or ranitidine inhibited the development of stress ulcers, reduced changes in ir-TRH concentrations in the gastric wall and gastric juice, and induced an increase in gastric pH. Omeprazole inhibited stress ulcer formation and changes in gastric wall and gastric juice ir-TRH concentrations. These results suggest that TRH release from the stomach wall into gastric juice is of importance in the pathogenesis of stress ulcer and that its release is mediated by both muscarinergic and histaminergic (H2) systems. Furthermore, omeprazole has an inhibitory effect on TRH release under stress ulcer.

Animals↗

Subclinical phenotypic expressions in heterozygous females of X-linked recessive bulbospinal neuronopathy.

Four of 8 definite heterozygous female carriers determined by PCR amplification of tandem CAG repeat of the AR gene, from 4 families of X-linked recessive bulbospinal neuronopathy (X-BSNP) showed extensive high amplitude motor unit potentials in examined muscles although all subjects were neurologically normal. Plasma creatine kinase, myoglobin, myosin light chain, lactate and pyruvate were all normal even in the carriers who showed EMG abnormalities. Muscle biopsy showed a type 2 fiber preponderance and possible very mild type 2 fiber grouping in a carrier with an EMG abnormality. These results suggest that a mutant AR gene may express subclinical phenotypic manifestations in a subpopulation of the heterozygous females of X-BSNP.

Action Potentials↗

In vivo stimulation of thyroid hormone release by rabbit antibodies with thyroid stimulating activity raised against the mutated receptor peptide TSH-R-HIS17.

The present study was designed to examine whether thyroid stimulating antibodies (TSAb) against the mutated or non-mutated peptide of human TSH receptor stimulates release of thyroid hormones in mice in vivo. We generated antibodies against mutated TSH receptor peptide TSH-R-HIS17 and non-mutated TSH receptor peptide TSH-R-ASP17 immunizing the peptides to rabbits. We isolated immunoglobulin G (IgG) from these antibodies and injected iv into male ddy mice. Control mice were injected iv with bTSH or TSAb-negative normal rabbit IgG. Serum T3 and T4 concentrations were elevated after the administration of bTSH in a dose-dependent manner. Serum T3 and T4 concentrations were significantly elevated after the injection of IgG from the rabbit antibodies with TSAb activity produced against TSH-R-HIS17. However serum T3 and T4 remained within normal levels after the injection of IgG from the rabbit antibodies without TSAb activity toward TSH-R-ASP17. The present data offer in vivo support of the IgG with TSAb activity interaction with the TSH receptor of the thyroid and raise the possibility that TSAb against mutated human TSH receptor peptide might be contributed to induce thyroid hyperfunction.

Amino Acid Sequence↗

Laminin A, B1, and B2 chain gene expression in transected and regenerating nerves: regulation by axonal signals.

Laminin A, B1, and B2 chain mRNA levels in degenerating and regenerating mouse sciatic nerves were examined using northern blot analysis. In normal intact nerves, B1 and B2 mRNA steady-state levels were high, but when the nerves were crushed, the steady-state levels of B1 and B2 mRNA per milligram wet tissue weight of the distal segments of the nerves increased five- to eightfold over that of control levels as the total RNA and beta-actin mRNA levels increased, suggesting that these increases were the consequence of Schwann cell proliferation after axotomy. When the steady-state levels of B1 and B2 mRNA were normalized as the ratio to total RNA or beta-actin mRNA levels, however, they drastically decreased to about 20% of the normal nerve levels in the nerve segments distal to both the crush and transection sites 1 day after injury. In the crushed nerves, B1 and B2 mRNA levels gradually increased as the regenerating nerves arrived at the distal segments and reestablished normal axon-Schwann cell contact, and then returned to normal levels on the 21st day. In the transected nerves, where Schwann cells continued to be disconnected from axons, both B1 and B2 mRNA levels remained low. Cultured Schwann cells expressed detectable levels of B1 and B2 chain mRNA which significantly increased when the cells were cocultured with sensory neurons. However, mRNA for A chain was not detectable in the normal, axotomized nerves or in cultured Schwann cells. These data indicate that Schwann cells express laminin B1 and B2 chain mRNA that are up-regulated by axonal or neuronal contact, but they do not express A chain mRNA.

Actins↗

Effects of immunoneutralization of endogenous opioid peptides on the hypothalamic-pituitary-thyroid axis in rats.

Effects of opioid peptide antisera treatment on the secretion of thyrotropin (TSH) and thyrotropin-releasing hormone (TRH) in rats were studied. Anti-beta-endorphin antiserum, anti-methionine-enkephalin antiserum, or antidynorphin antiserum was injected intraperitoneally and the rats were serially decapitated. TRH levels in the hypothalamus along with plasma TRH, TSH and thyroid hormone levels were measured by individual radioimmunoassay. TRH contents in the hypothalamus decreased significantly after opioid peptide antisera treatment, while its plasma levels tended to decrease, but not significantly. Plasma TSH levels increased significantly after opioid peptide antisera injection. Plasma TRH and TSH level responses to cold as well as plasma TSH level response to TRH were enhanced with treatment of antisera to these peptides. Plasma 3,3',5-triiodothyronine levels increased significantly after treatment of antisera to these peptides. From these findings it is concluded that the treatment of opioid peptide antisera stimulates TRH and TSH secretion in rats.

Animals↗

Pituitary resistance to thyroid hormone associated with a base mutation in the hormone-binding domain of the human 3,5,3'-triiodothyronine receptor-beta.

Point mutations in the human T3 receptor-beta (TR beta) gene causing single amino acid substitutions have been identified in several different kindreds with generalized resistance to thyroid hormone. Until now, no study has been reported on the TR gene in cases of pituitary resistance (PRTH). In the present study, we analyzed the TR beta gene in a 30-yr-old Japanese female with PRTH. She exhibited clinical features of hyperthyroidism, elevated serum thyroid hormone levels accompanied by inappropriately increased secretion of TSH, mildly elevated basal metabolic rate, and increased urinary excretion of hydroxyproline. No pituitary tumor was detected. DNA fragments of exons 3-8 of the genomic TR beta gene were generated by the polymerase chain reaction and analyzed by a single stranded conformation polymorphism method. Exon 7 of the patient's TR beta gene showed an abnormal band, suggesting the existence of mutation(s). By subcloning and sequencing the DNA, a point mutation was identified in one allele at nucleotide 1297 (C to T), which altered the 333rd amino acid, arginine, to tryptophan. Neither of her apparently normal parents had any mutations of the TR beta gene. In vitro translation products of the mutant TR beta gene showed remarkably decreased T3-binding activity (Ka, 2.1 x 10(8) M-1; normal TR beta Ka, 1.1 x 10(10) M-1). Since the molecular defect detected in a patient with PRTH is similar to that seen in subjects with generalized resistance to thyroid hormone, both types of the syndrome may represent a continuous spectrum of the same etiological defect with variable tissue resistance to thyroid hormone.

Adult↗

Skin sympathetic nerve activity in acquired idiopathic generalized anhidrosis.

We recorded skin sympathetic nerve activity (SSNA) microneurographically from the right tibial nerve of a patient with acquired idiopathic generalized anhidrosis (AIGA). The patient did not show any spontaneous sweating or pilocarpine- and nicotine-induced sweat response. Histopathologic examination showed degenerated eccrine glands associated with surrounding inflammatory cellular infiltration. Electrical nerve stimulation produced a two-peak pattern of SSNA reflex discharge representing sudomotor and vasoconstrictor components. The frequency of spontaneous SSNA bursts (burst rate), presumably of a sudomotor nature, at the ambient temperature of 25 degrees C was significantly higher than in a healthy control subject and was further increased at a temperature of over 38 degrees C. Thus, sudomotor sympathetic nerve activity is well preserved or even increased in AIGA. We conclude that anhidrosis of AIGA results from the generalized sweat gland dysfunction rather than decreased sympathetic outflow to the skin.

Adult↗