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Biomedical subjects

T Mitsuma

Publications and source records attributed to T Mitsuma.

At least 19 recordsLinked to original sources

Severity of X-linked recessive bulbospinal neuronopathy correlates with size of the tandem CAG repeat in androgen receptor gene.

The genetic mutation of X-linked recessive bulbospinal neuronopathy is amplification of a polymorphic tandem CAG repeat in the androgen receptor gene. We studied this CAG repeat in 26 Japanese patients from 21 families with X-linked recessive bulbospinal neuronopathy. The number of CAG repeats was significantly correlated with the age at onset of limb muscular weakness (r = -0.596, p < 0.001) and age-adjusted scored disability (r = 0.446, p < 0.03). The length of the CAG repeat therefore seems to be a determinant factor of clinical severity.

Adult

Phosphorylated high molecular weight neurofilament protein in the peripheral motor, sensory and sympathetic neuronal perikarya: system-dependent normal variations and changes in amyotrophic lateral sclerosis and multiple system atrophy.

Using monoclonal antibody (Ta-51) that specifically binds phosphorylated high molecular weight neurofilament (pNFH) proteins, we investigated the occurrence of perikaryal pNFH in the spinal ventral horn motoneurons, intermediolateral column (ILC) neurons, sympathetic ganglion neurons and dorsal root ganglion (DRG) neurons obtained from patients with amyotrophic lateral sclerosis (ALS) and multiple system atrophy (MSA) and from control cases. In the controls, a system-dependent variation in perikaryal Ta-51 immunoreactivity was observed. Very few ventral horn cells and ILC neurons were stained with Ta-51, while large population of DRG neurons and sympathetic neurons were Ta-51 positive. The incidence of perikaryal immunoreactivity in the ventral horn cells was significantly increased in ALS and MSA. Some ILC neurons in ALS were Ta-51 positive and their incidence was significantly higher than that of the controls. These data suggest that both ILC neurons and ventral horn cells are affected with respect to pNFH metabolism in ALS and MSA. No significant difference was, however, detected in the Ta-51 immunoreactivity of both DRG and sympathetic ganglion neurons in ALS and MSA as compared with the controls.

Adult

Extensive demyelinating changes in the peripheral nerves of Crow-Fukase syndrome: a pathological study of one autopsied case.

Pathological changes of the peripheral nervous system in one autopsied case of Crow-Fukase syndrome (POEMS syndrome) was systemically examined. Distally accentuated myelinated axon loss was observed in the peripheral nerve trunks, ventral and dorsal spinal roots, but was not observed in the fasciculus gracilis. Segmental demyelination and remyelination associated with focal excessive myelin outfolds were the most characteristic features, the distribution of which was more prominent in the proximal nerve trunks and the spinal nerve roots. Endoneurial edema was present, and focal perivascular T lymphocyte accumulation was occasionally observed in the spinal nerve roots and proximal nerve trunks. Neurons in the sympathetic ganglia, dorsal root ganglia and ventral horns were well preserved.

Aged

Helicobacter pylori infection induces a decrease in immunoreactive-somatostatin concentrations of human stomach.

Immunoreactive-somatostatin (ir-somatostatin) concentrations of the gastric mucosa and gastric juice with Helicobacter pylori infection were measured in the human stomach. One hundred seventy-one patients (106 males, 65 females; mean age, 52.0; range, 19-84 years) were registered. Gastric juice and mucosa were obtained with the usual endoscopy procedure. Somatostatin concentration was measured by radioimmunoassay. The ir-somatostatin concentrations in the H. pylori-negative group were significantly higher than in the positive group gastric mucosa, whereas its levels in gastric juice tended to decrease with H. pylori infection. There was an inverse correlation between luminal ammonia levels and ir-somatostatin concentrations of the gastric mucosa. On the other hand, ir-somatostatin concentrations of the gastric mucosa significantly decreased with chronic and active inflammatory change. This decrease was not correlated with the grade of active inflammation, which was in close relation to H. pylori infection, but with the grade of chronic inflammation. These results indicate that H. pylori may reduce ir-somatostatin concentrations of the human stomach and that its effect is partly mediated via luminal ammonia produced by H. pylori.

Adult

Effect of luminal administration of thyrotropin-releasing hormone or somatostatin on gastric pH and interaction of these peptides in rats.

The effect of intraluminal administration of thyrotropin-releasing hormone (TRH) on gastric pH and release of luminal somatostatin, and a possible interrelationship between TRH and somatostatin in the rat stomach were studied. TRH was administered into the stomach via an intragastric tube at various doses (50 pg/kg-10 micrograms/kg) and gastric pH was measured after 15 min. The intraluminal administration of TRH significantly decreased gastric pH at doses over 1.0 ng/kg. Time-course studies at a dose of 100 ng/kg TRH exhibited a significant decrease in gastric pH at 15, 30 and 60 min. Furthermore, TRH administration caused a significant increase in immunoreactive-somatostatin (ir-somatostatin) concentrations in the gastric wall and a significant decrease in ir-somatostatin concentrations in the gastric juice. On the other hand, intraluminal administration of somatostatin caused a significant increase in ir-TRH concentrations in the gastric wall and a significant decrease in ir-TRH concentrations in the gastric juice, and significantly raised gastric pH at 5 min. These findings suggest that luminal TRH may exert a regulatory effect on gastric acid secretion, and that TRH may have a possible interaction with somatostatin in the modulation of gastric acid secretion.

Animals

Somatic motor efferents in multiple system atrophy with autonomic failure: a clinico-pathological study.

The myelinated fibers in the corticospinal tracts, ventral spinal roots, and the neurons in the ventral spinal horns were quantitatively examined in 8 autopsied cases of multiple system atrophy associated with autonomic failure. In these structures consisting of the somatic motor efferents, the main pathological feature was the size dependent-involvement of predominantly small-sized fibers and neurons. The small myelinated fibers were significantly depopulated, while the large myelinated fibers were well populated in the corticospinal tract. Neurons in the ventral horns were also involved, but those with a small diameter and located in the intermediate zone (Rexed's lamina VII, VIII) were markedly diminished. In the ventral spinal roots, in the fourth lumbar segments containing essentially no autonomic efferents, small myelinated fibers were also preferentially involved. These pathological changes in the small-sized fiber and neuron loss were examined in relation to the somatic and autonomic motor symptoms, particularly of pyramidal signs.

Aged

Effects of acetylcholine on the release of thyrotropin-releasing hormone from the rat retina in vitro.

Effects of acetylcholine on the release of thyrotropin-releasing hormone (TRH) from the rat retina were studied in vitro. The retina was incubated in medium 199 (pH 7.4) with 1.0 mg/ml of bacitracin and 100 micrograms/ml of ascorbic acid (medium) for 20 min. The amount of TRH release into the medium was measured by radioimmunoassay. The TRH release from the rat retina was enhanced significantly in a dose-related manner with the addition of acetylcholine and inhibited with addition of atropine. The stimulatory effect of acetylcholine on TRH release from the retina was blocked with the addition of atropine. The elution profile of methanol-extract of the rat retina was identical to that of synthetic TRH. The findings suggest that the cholinergic system stimulates TRH release from the rat stomach in vitro.

Acetylcholine

Effects of dopamine on the release of thyrotropin-releasing hormone from the rat retina in vitro.

The effects of dopamine on the release of thyrotropin-releasing hormone (TRH) from the rat retina in vitro were studied. The rat retina was incubated in the medium 199 (pH 7.4) with 1.0 mg/ml of bacitracin and 100 micrograms/ml of ascorbic acid. The amount of TRH release into the medium was measured by radioimmunoassay. The TRH release from the rat retina was inhibited significantly in a dose-related manner with the addition of dopamine, but not with pimozide. The inhibitory effects of dopamine on TRH release from the rat retina were blocked with an addition of pimozide to the medium. The elution profile of methanol-extracted rat retina on sephadex G-10 was identical to that of synthetic TRH. From these findings it is concluded that the dopaminergic system inhibits TRH release from the rat retina in vitro.

Analysis of Variance

Effect of serotonin on the immunoreactive thyrotropin-releasing hormone concentrations of the rat stomach.

The effects of serotonin and its related compounds on immunoreactive thyrotropin-releasing hormone (ir-TRH) concentrations of the rat stomach wall and gastric juice were studied. Either serotonin, cyproheptadine or GR38032F was injected intraperitoneally, and the rats were decapitated at various times after the injection. ir-TRH concentrations of the stomach wall and gastric juice were measured by radioimmunoassay, and gastric serotonin concentrations were measured by HPLC. ir-TRH concentrations of the stomach wall decreased, and ir-TRH concentrations of gastric juice increased significantly after serotonin injection. On the other hand, both cyproheptadine and GR38032F did not affect ir-TRH concentrations of the stomach. The effects of serotonin on ir-TRH concentrations of the stomach were significantly blocked by the pretreatment of cyproheptadine and GR38032F. The reciprocal changes of gastric ir-TRH and serotonin concentrations were observed without changes in gastric juice pH. These findings suggest that serotonin stimulates ir-TRH release from the stomach wall into gastric juice, and the effects of serotonin on ir-TRH release may be partly mediated via 5-HT2- and 5-HT3-receptors.

Animals

Hyperparathyroidism associated with parkinsonism.

A 70-year-old woman with hyperparathyroidism associated with parkinsonism is reported. Her primary initial symptom was parkinsonism, but it was levodopa-resistant. Chemical and hormonal findings revealed that she had hyperparathyroidism. The symptoms were relieved after the surgical removal of a parathyroid adenoma. Although this type of case has been reported only rarely, it suggests that hypercalcemia might be an aggravating factor in levodopa-resistant parkinsonism.

Adenoma

[Quantitative skeletal muscle pathology of aging regarding ragged-red fibers and cytochrome c oxidase-negative fibers].

A statistical analysis of mitochondrial abnormality of aging in human skeletal muscle fibers was performed. Sixty one muscle samples were obtained from patients with acute medical illness autopsied strictly within 2 hours after death, or with orthopedic or surgical diseases biopsied with informed consents. The patients aged from 16 to 89, averaging 58 +/- 21 years in males and 21 to 92, averaging 55 +/- 20 years in females. Sections were stained by modified Gomori's trichrome, succinate dehydrogenase and cytochrome c oxidase-negative [CCO(-)] fibers approximately in 10,000 fibers in each muscle were evaluated. Both RRF and CCO (-) fibers were not observed below the fourth decade, but sequentially increased with age, especially after the seventh decade. The incidence of CCO (-) fibers was higher than that of RRF. RRF did not necessarily correspond to CCO (-) fibers. The present quantitative pathological result is a useful tool to evaluate the mitochondrial function in fresh human skeletal muscles by the age.

Adolescent

[Effect of a long-term oral ammonia administration on immunoreactive-somatostatin concentrations of rat stomach].

The effect of a long-term oral ammonia administration on immunoreactive-somatostatin concentrations was investigated in rat stomach. The gastric ir-somatostatin concentrations in the group treated with 0.01% ammonia (pH 9.6) for four weeks were significantly higher than those in both the group treated with 0.1% ammonia (pH 10.4), 0.1 mM-NaOH (pH 9.6), or distilled water (pH 7.0) for four weeks and the group treated with 0.01% ammonia for two weeks. On the contrary, ir-somatostatin levels in the gastric juice and serum tended to decrease with ammonia administration. Further, ammonia administration significantly induced the decrease in mucosal thickness in the pyloric gland area and parietal cell numbers in a dose- and time-dependent manner. From these findings, it was suggested that a long-term oral treatment with 0.01% ammonia, which was clinically estimated as the concentration of the gastric juice in patients with Helicobacter pylori infection, induced not only atrophic changes on gastric mucosa, but the inhibitory effect on somatostatin secretion in rat stomach.

Administration, Oral

[The corticospinal tract of amyotrophic lateral sclerosis--a morphometric analysis of the myelinated fibers].

The myelinated fibers in the lateral corticospinal tract at the C6, T7, L4 levels in amyotrophic lateral sclerosis (ALS) and control cases were morphometrically examined. ALS cases consisted of 6 males and 2 females with ages ranging between 48 and 85 years, and were all the common or bulbar form in clinical manifestation. As for controls, 10 cases who died of non-neurological diseases, with age ranging 36 to 90 years were served. The population and the diameter profile of the myelinated fibers in the corticospinal tract of the C6, T7, L4 levels were measured by the method previously described and expressed as number per mm2. In control subjects, fiber-size histograms of myelinated fibers showed a bimodal pattern with a sharp peak of small fibers (less than 7.28 microns) and a broad peak of large fibers (greater than or equal to 7.28 microns) in all the spinal levels. In ALS cases, large myelinated fibers were predominantly diminished in number, a small myelinated fibers were also decreased in some cases. The degree of fiber loss was extremely variable among cases; well populated in large fibers in some cases. As for the rostral caudal distribution of myelinated fiber loss, a caudally-accentuated fiber loss particularly in large fiber was seen in some of the cases. The topographical distribution of fiber loss in the horizontal plane of the corticospinal tract in ALS did not show a distinctive pattern.

Aged

[Involvement of the ventral horn cells in Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuritis].

The lumbar ventral horn cells and myelinated fibers in the ventral spinal roots of Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuritis (CIDP) were morphometrically analyzed. In all six cases, central chromatolytic changes in the ventral horn cells were commonly observed. In addition, two out of four GBS cases and one of two CIDP cases showed a significant reduction in the ventral horn cell population, particularly in neurons with a large diameter. The cases with significant motoneuron loss also showed a remarkable reduction in the number of myelinated fibers in the ventral spinal roots, and severe axonal degeneration was observed in cases in acute phase. Astrogliosis of the ventral horn was also seen in some cases. The present study suggested that motoneuron loss in the primary demyelinating diseases like GBS and CIDP is the consequence of the axonal pathology of the motoneuron axons. These observations are helpful to understand motoneuron loss in certain motoneuron diseases with preferential involvement of lower motor neurons.

Adult

Effects of dexamethasone on TRH and TRH precursor peptide (Lys-Arg-Gln-His-Pro-Gly-Arg-Arg) levels in various rat organs.

The effect of an acute dexamethasone administration on thyrotropin-releasing hormone (TRH) and TRH precursor peptide (Lys-Arg-Gln-His-Pro-Gly-Arg-Arg) (p-8) levels in various rat organs has been studied. Rats were injected i.p. with 25 micrograms of dexamethasone/100 g body weight (group A), 500 micrograms of dexamethasone/100 g body weight (group B) or saline (group C). The rats were serially decapitated after the injection. TRH and p-8 levels in the hypothalamus, cerebrum, cerebellum and brain stem, stomach and eye and plasma TRH and thyrotropin (TSH) levels were measured by individual radioimmunoassays. P-8 levels in the hypothalamus decreased significantly in both group A and B at 1-4 hours after the injection, and then returned to pretreated levels at 24 hours after the injection. TRH levels in the hypothalamus increased significantly in both group A and group B at 1-4 hours after dexamethasone injection. No changes in p-8 and TRH levels were observed in other organs. In group A, plasma TRH levels tended to decrease at 1-2 hours, then to increase at 3 hours. In group B, plasma TRH levels decreased 1-4 hours after the dexamethasone injection, then increased at 24 hours. The plasma TSH levels decreased significantly at 1-4 hours in group A and group B, returned to pretreatment levels at 24 hours in group A, and increased significantly in group B at 24 hours after dexamethasone injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence

[Autonomic facio-cephalalgia].

Autonomic facio-cephalalgia was first described by Brickner et al. in 1935. At that time, it's clinical picture was characterized as pain seizure in the head or face unilaterally with various autonomic signs, such as swelling, redness and hyperthermia of the painful regions. After the first case was described, few cases have been reported, including our two cases. Thus, it's definite clinical entity can not be determined at present. In this review, the history, symptoms, signs, differential diagnosis of this disease and details of two our cases are described. The clinical entity of this disease, on bases of present knowledge is discussed.

Adult

[DNA diagnosis of X-linked recessive bulbospinal muscular atrophy by androgen receptor gene mutations].

X-linked recessive bulbospinal muscular atrophy (BSMA) is an adult-onset form of motor neuron disease, of which androgen receptor (AR) gene mutations with increased size of a polymorphic tandem CAG repeat in the coding region was found by Fischbeck et al (1991). We investigated this AR gene abnormality by polymerase chain reaction (PCR) in 16 unrelated Japanese BSMA pedigrees, including 21 patients, 11 male siblings without any neurological signs and 9 female siblings. PCR products for AR-CAG repeat obtained from 21 affected individuals were enlarged in fragment size (about 100 bp longer than normal control size), whereas those from clinically unaffected brothers of the patients and their offsprings were all normal in size. Moreover, PCR products from 8 obligate heterozygous females (carriers) consisted of two different fragments with enlarged and normal size. Our results confirmed the findings reported by Fischbeck et al, and indicated that the detection of this AR gene mutations with increased size of a polymorphic tandem CAG repeat is beneficial for pre-onset diagnosis or carrier detection of this disease.

Adolescent