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Biomedical subjects

T Mitsuma

Publications and source records attributed to T Mitsuma.

At least 109 records · Page 6Linked to original sources

[Peptidergic sweating in multiple system atrophy and hereditary spinocerebellar ataxia with special reference to calcitonin gene-related peptide].

Calcitonin gene-related peptide (CGRP)-like immunoreactivity has been demonstrated to be present in nerve terminals around the sweat glands. We have previously demonstrated that CGRP modulates the cholinergic sweating activity. The present study was designed to evaluate the locally administrated CGRP on sweating of patients with multiple system atrophy (MSA) and hereditary spinocerebellar ataxia (HSCA) consisting of 10 males and 11 females. Among 9 HSCA, 3 was diagnosed as Machado-Joseph disease by clinical and DNA diagnostic assessment. CGRP and methacholine chloride (MCH) was dissolved in saline solution to specified concentration, and 0.1ml of which was injected intradermally at the center of a forearm test area. The sweat rate was recorded continuously by the capacitance hygrometry in a relatively cool environment in which the spontaneous sweating was absent. CGRP significantly increased the sweat rate when it was administrated with MCH on normal subjects. There was a clear dose-dependent relationship between the dose of CGRP and its enhancement. This enhancement was significantly reduced in patients with MSA as compared with controls. On the other hand, most of HSCA showed no remarkable impairment of CGRP enhancement. These results suggest that peptidergic sweating is extensively affected in patients with MSA but is not in patients with HSCA, which may be the consequence of peptidergic sweating dysfunction in MSA.

Adult↗

[Somatoparaphrenia caused by the lesion in the dominant cerebral hemisphere--a case report].

We reported a rare case of cerebral infarction with somatoparaphrenia (SP) caused by involvement of the dominant cerebral hemisphere. The patient was 77-year-old right-handed woman who was noted to have atrial fibrillation, right hemiplegia, hemisensory disturbance and ipsilateral homonymous hemianopsia. Neuropsychologically, there were anosognosia (AG) for hemiplegia and SP arguing her hand as doctor's hand. In addition, there also were noted disorientation, right unilateral spatial neglect and mild amnestic aphasia. Brain CT and MRI demonstrated infarctions in the left lateral thalamus, internal capsule, lateral geniculate body, hippocampus, caudate nucleus and medial occipitotemporal gyrus. IMP-SPECT showed extensive hypoperfusion areas in the left cerebral hemisphere. These lesions were thought to have resulted from occlusion of the left anterior choroidal artery and partial occlusion of the left middle and posterior cerebral arteries caused by cardiogenic embolism. AG persisted and SP disappeared 80 days after the onset. While AG and SP are generally believed to be associated with non-dominant hemispherical lesion, the present case suggests the possibility that those symptoms were seen in the case of dominant hemispherical lesion without severe aphasia.

Aged↗

[Immunostaining of anti-Bcl-2 antibody in diseased human muscles].

Immunostaining of Bcl-2 protein which represses apoptosis was performed on 178 biopsied human pathologic muscles and 10 control muscles by the ABC method using two monoclonal anti-Bcl-2 antibodies. Bcl-2 in control muscles was positive mainly in nuclear membrane and cytoplasm in type 2 fibers (especially type 2B fibers), and negative in type 1 fibers. In myopathies, it was not expressed in type 2C (regenerating) fibers, and its expression in atrophic fibers such as forming pyknotic nuclear clumps was strong. In inflammatory myopathies, expression was observed in infiltrating lymphocytes, and especially in dermatomyositis in atrophic fibers facing perimysium. In mitochondrial myopathies, the positivity was observed only in type 2 ragged-red fibers. In muscles of neurogenic disorders, both small angulated fibers and atrophic grouped fibers were strongly positive. Western blot analysis using anti-Bcl-2 antibody showed a single band at 26 kDa in control and diseased skeletal muscles. Compared to immunostaining of Fas antigen in serial sections, both Bcl-2 and Fas were expressed in same atrophic fibers in distal myopathy with rimmed vacuoles. In myotonic dystrophy, they were often expressed in type 2 fibers containing internal nucleus. In carriers of Duchenne dystrophy, Fas-positive but Bcl-2 negative fibers were observed in same dystrophin-negative fibers. In conclusion, expression of Bcl-2 in skeletal muscles might suggest that Bcl-2 plays a role on surviving muscle fibers.

Apoptosis↗

[Clinical features of anterior inferior cerebellar artery territory infarcts--a study of ten patients].

Clinical features of the anterior inferior cerebellar artery (AICA) territory infarcts were investigated in ten patients, ranging in age from 38 to 76 years. In all patients, there were MR images of infarction located in the area supplied by the AICA. The lesion was on the left side in 6 patients and right side in 4. The lesion of brain stem including the middle cerebellar peduncle was found in 7 patients and that extended to the cerebellum was in 3 patients. The main ipsilateral neurological signs were the VII and VIII cranial nerves palsy and cerebellar ataxia. The V and VI cranial nerves palsy. Horner's syndrome, and dysphagia were also present. The main contralateral sign was superficial sensory disturbance, but no hemiplegia. The underlying pathology included chiefly hyperlipidemia, hypertension, and diabetes mellitus. Cerebral angiography was performed in 8 patients, most of which was observed severe arteriosclerosis suggesting poor hemodynamics in the vertebral and basilar arteries. The prognosis was relatively good, but the VII, VIII, and V cranial nerves palsy and contralateral superficial sensory disturbance remained as the sequelae. As mentioned above, there were various neurological findings and MR images in AICA territory infarcts. Especially there were some patients whose lesion extended to the upper medulla and neurological findings were similar to the Wallenberg syndrome. It is important that one investigates not only axial slices but also coronal slices of MR image to estimate the extension of AICA territory infarct.

Adult↗

[Central facial weakness due to medullary pyramidal infarction; a case report].

We reported a hypertensive 40-year-old man who developed sudden right hemiparesis, deep sensory disturbance, left hypoglossal nerve palsy, and mild right central facial weakness. MRI of the brain showed an infarct located in the left upper medullary pyramid. Course and connection of the corticobulbar pathway are not well known in human. Recently Cavazos (1996) described a hypothesis that some facial corticobulbar fibers descend caudally ipsilaterally as low as the upper medulla, making a loop before decussating and ascending to the contralateral facial nucleus Contralateral central facial weakness may result from interruption of these descending fibers.

Adult↗

Primary sensory neurons in X-linked recessive bulbospinal neuropathy: histopathology and androgen receptor gene expression.

Pathology of the primary sensory neurons was examined in 7 autopsied patients and 6 biopsied sural nerves from the patients with X-linked recessive bulbospinal neuronopathy (SBMA). Large myelinated fibers in the central rami (L-4 posterior root, L-4, T-7, and C-6 segment of the fasciculus gracilis), and in the peripheral rami (sural nerve) were diminished in a distally accentuated manner, while small myelinated and unmyelinate fibers were well preserved in number. Demylinating process and axonal atrophy was ubiquitous. The diameter frequency histograms of the dorsal root ganglion (DRG) neurons showed a decrease in the number of large diameter neurons and an increase in the number of small diameter neurons without substantial loss of whole number of neurons, which suggested that neuronal size was atrophied. These data suggested central and peripheral distal axonopathy with neuronal atrophy was the process of sensory neuron involvement. Expression of mutant androgen receptor mRNA with elongated CAG repeat in the DRG and sural nerve supported the view that sensory nerve involvement is the primary process in SBMA.

Aged↗

X-linked recessive bulbospinal neuronopathy: clinical phenotypes and CAG repeat size in androgen receptor gene.

Clinical phenotypes and the CAG repeat size of the androgen receptor gene were assessed in 95 Japanese patients with X-linked recessive bulbospinal neuronopathy. There was an age- and duration-dependent deterioration of muscle strength, ADL scores, and plasma creatine kinase levels. However, there was no correlation between the presence of absence of gynecomastia or diabetes mellitus and the age at onset or duration of illness. Correlations were present between the CAG repeat size and the age at onset (P < 0.0001) as well as the presence or absence of gynecomastea (P < 0.05). Muscular weakness and ADL scores were also correlated with the CAG repeat size only when they were adjusted by the age at examination not by the duration of illness. These findings suggest that CAG repeat size is one of the determinant factors of disease progression. However, extensive variation in phenotypic severity in patients with the same size of CAG repeat was present even among the siblings, suggesting that other factors than CAG repeat size influence the phenotypic manifestation. The average gain of CAG repeat size expansion was a 1.4 repeat in paternal transmission which was more unstable than that in maternal transmission, but the magnitude of the expansion in paternal transmission was much smaller than is presently known for other diseases in which CAG repeat expansion is the responsible gene defect.

Adolescent↗

Effect of plaunotol on hypergastrinemia induced by long-term omeprazole administration in humans.

Omeprazole markedly inhibits basal and stimulated gastric acid secretion and has the ability to produce hypergastrinemia and hyperplasia of enterochromaffin-like cells in humans. On the other hand, plaunotol, an acyclic diterpene alcohol, has been reported to inhibit gastrin release by stimulating endogenous secretion release. We investigated the effect of plaunotol on serum gastrin levels after six to eight weeks of omeprazole (20 mg/day) administration in 22 patients (16 males, 6 females; mean age 52.3, range 36-70 years) with peptic ulcer disease. The patients were randomized to the following two groups: 11 subjects with omerprazole alone (single group) and 11 with omeprazole plus plaunotol (240 mg/day) (combination group) treatment. There were no significant differences between the two groups concerning age, sex, ulcer stage, ulcer history, environmental factors, and Helicobacter pylori (HP) prevalence. After complete drug(s) administration, serum immunoreactive (ir) -gastrin levels increased significantly in the single group (P < 0.001) in contrast to the combination group, and plaunotol significantly inhibited hypergastrinemia induced by omeprazole administration (P < 0.001). Significant increases in serum ir-calcitonin gene-related peptide concentrations were observed in the combination group compared to the single group (P < 0.05). However, there were no significant changes in sereum ir-secretin, somatostatin, and vasoactive intestinal polypeptide levels as well as ulcer healing and HP prevalence between the two groups. These findings suggest that plaunotol may suppress hypergastrinemia induced by long-term omeprazole administration, at least partly, via a certain brain-gut hormone affecting gastrin release.

Adult↗

Nizatidine accelerates gastric emptying of a solid meal in rats.

Nizatidine, a new histamine-2-receptor antagonist, stimulates gastrointestinal motility in dogs and gastric emptying of liquids in rats. Effect of nizatidine on gastric emptying of a solid meal was investigated using a novel gastric emptying model in rats. Male Wistar rats (weighing 200-300 g) were supplied with powdered food containing 30 w/w% barium 14 hr before the beginning of the experiment and x-ray photography of rat stomach was taken under light ether anesthesia. Gastric emptying was assessed by percentage of a decrease in area 30 min after drug was injected intraperitoneally. There was a positive correlation between the area of the gastric outline and the weight of the gastric contents (r = 0.94, P < 0.01). Ether anesthesia itself did not affect gastric emptying. Nizatidine increased gastric emptying dose-dependently (emptied percentage; vehicle: 4.9 +/- 1.5%, 1 mg/kg: 7.2 +/- 0.4%, 3 mg/kg: 10.4 +/- 2.0%, 10 mg/kg: 16.7 +/- 4.9%, 30 mg/kg: 25.7 +/- 7.4%). N-Desmethyl nizatidine (NDM) also stimulated gastric emptying, but nizatidine S-oxide, cimetidine, an famotidine had no significant effects on gastric emptying. Nizatidine and neostigmine, but not NDM, at a subthreshold dose accelerated gastric emptying treated with a low dose of acetylcholine (0.1 mg/kg). Atropine (2 mg/kg, -30 min) did not modulate the gastroprokinetic action of nizatidine, but blocked that of NDM. These findings suggest that this noninvasive method may allow measurement of gastric emptying of solids accurately and that nizatidine and NDM facilitate gastric emptying probably mediated by a direct and/or an indirect (acetylcholinesterase inhibition) cholinergic mechanism.

Acetylcholine↗

Effect of cold-restraint stress on immunoreactive thyrotropin-releasing hormone and immunoreactive somatostatin in the rat stomach.

The effects of cold-restraint stress on immunoreactive thyrotropin-releasing hormone (ir-TRH) and immunoreactive somatostatin (ir-SOM) concentrations in the rat stomach were investigated. Rats immobilized with a spring-loaded metallic plate were placed in a room maintained at 4 degrees C for 1-3 h and then decapitated serially for investigation. Gastric ir-TRH and ir-SOM concentrations were measured by individual radioimmunoassays. Cold-restraint stress induced gastric mucosal lesions as well as a decrease of the ir-TRH concentration in the glandular stomach, an increase of the ir-TRH concentration in the gastric juice, and a decrease in gastric pH. In contrast, this stress caused an increase of ir-SOM in the glandular stomach and a decrease of ir-SOM in the gastric juice. However, cold or restraint stress alone did not induce gastric mucosal lesions or changes in gastric ir-TRH and ir-SOM concentrations or the gastric pH. To clarify the endocrine influence of peripheral TRH, pretreatment with thyroid hormone was performed to inhibit elevation of the serum TRH level during cold-restraint stress. Despite this pretreatment, cold-restraint stress still induced ulcer formation, along with changes in gastric ir-TRH and ir-SOM concentrations and gastric pH. These findings suggest that changes in gastric ir-TRH and ir-SOM concentrations may be closely related to ulcer formation due to cold-restraint, and that TRH may act in a paracrine manner in the stomach.

Animals↗

Magnetic resonance imaging of the corticospinal tracts in amyotrophic lateral sclerosis.

In 13 patients with amyotrophic lateral sclerosis (ALS), corticospinal tract lesions on spinal cord, brain and brain stem were examined by MR imaging. In 9 patients, areas of high signal intensity located in the dorsolateral columns coinciding with the lateral corticospinal tracts, were detected on axial T2*-weighted MR imaging of the cervical spinal cord using a gradient echo technique. In two patients, these spinal cord MR abnormalities corresponded well to the postmortem pathological findings of lateral corticospinal tract degeneration. T2-weighted abnormal MR signals along the corticospinal tract at the brain and brain stem were detected in 4 patients, all of whom also showed abnormal signals on cervical cord MR imaging. Four of 13 patients did not show any abnormal signals on brain and brain stem or spinal cord MR imaging. Spinal cord MR imaging provides a useful information regarding upper motor neuron lesions in ALS.

Adult↗

Plasma exchange in chronic inflammatory demyelinating polyradiculoneuropathy; different beneficial effects and their correlation to the clinical features.

We report 7 patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) who showed significant clinical improvement by plasma exchange (PE). Their clinical features were extensively varied but fulfilled the diagnostic criteria for CIDP. The patients could be divided into 2 subgroups based on the mode of effectiveness of PE; one group consisted of those who once achieved complete remission, but required highly frequent PEs for long-term maintenance of remission and the others were those who showed persistent and complete remission with several sessions of PE alone. These findings raise issues about the long-term therapeutic goals to be achieved by PE for CIDP patients, particularly on supportive therapy other than PE, as well as the optimization of frequency and duration of PE.

Adult↗

Distribution of thyrotropin releasing hormone receptor in rats: an immunohistochemical study.

Thyrotropin releasing hormone (TRH) receptor was identified immunohistochemically in the rat tissues using anti-peptide antiserum. Anti-TRH receptor antiserum was raised in New Zealand white rabbits immunized with a conjugate of synthetic TRH-receptor peptide (15-28) to bovine serum albumin. Immunohistochemical analysis was performed by the avidin-biotin complex method. TRH-receptor immunoreactivity was visualized in the central nervous system and anterior pituitary thus supporting previous investigations of TRH receptor distribution using in vitro autoradiographic ligand binding. Significant stain was detected in neural perikarya, axons and dendrites as well as in many cells of the retina, adrenal medulla, stomach mucosa, Auerbach's nervous branch and Mysner's nervous branch of the stomach, small intestine and colon. When using antiserum preincubated with synthetic TRH-receptor peptide (15-28) or rat anterior pituitary homogenate which contains TRH-receptor peptide, no significant stain of the anterior pituitary cells or neurons in the hypothalamus was detected. These findings suggest that TRH-receptor is widely distributed and that this method is valuable in studying the distribution of TRH-receptor in rats.

Journal Article↗

Distribution of somatostatin receptor type 1 in the rat. An immunohistochemical study.

Somatostatin receptor type 1 (SSTR-1) was identified immunohistochemically in the rat tissues using anti-peptide antiserum. Anti-somatostatin receptor antiserum was raised in New Zealand white rabbits immunized with a conjugate of synthetic SSTR-1 peptide (41-52) with bovine serum albumin. Immunohistochemical analysis was performed by the ABC method. SSTR-1 immunoreactivity was visualized in the central nervous system, anterior pituitary, mucosa of stomach and duodenum, Auerbach's nervous branch and Mysner's nervous branch of gastrointestinal tract and pancreas. Significant staining was detected in neural perikarya, axon and dendrite. When using antiserum preincubated with synthetic SSTR-1 peptide (41-52) or rat anterior pituitary homogenated which contains SSTR-1, no significantly stained anterior pituitary cells or neurons in the hypothalamus were detected. These findings suggest that SSTR-1 is widely distributed and that this method is valuable in studying the distribution of somatostatin receptor in rats.

Journal Article↗

[Abnormality of PMP-22 gene in Japanese patients with Charcot-Marie-Tooth disease--comparison between Southern blot and polymerase chain reaction analysis in the detection of PMP-22 gene duplication].

We investigated the duplication of the PMP-22 gene in 23 Japanese patients with Charcot-Marie-Tooth disease (CMT) by Southern blot and PCR analysis. To detect duplication of the PMP-22 gene region, PMP-22 cDNA and a polymorphic marker, VAW409R3, located in the region flanking the PMP-22 gene, were used as probes for Southern blot analysis. A marker, 6G1, also located in the PMP-22 flanking region, was amplified using the quantitative PCR method. The signal intensity of the 2.8-kb and 2.7-kb bands of MspI digests probed with VAW409R3 was different in patients with duplication. The ratio of these two bands, measured by densitometry, ranged from 1.75 to 2.13 in the patients with duplication and from 1.01 to 1.15 in those without duplication and in normal controls. The signal ratio of PMP-22 to the reference marker SF85 of BamHI digests ranged from 1.15 to 1.33 in the patients with duplication and from 0.96 to 1.04 in those without duplication, when compared with normal controls assigned a value of 1.0. The ranges of the intensity in these two groups were narrow, but did not overlap. The signal ratio of the PCR products of 6G1 to reference marker D1S80 on quantitative PCR analysis was also measured. The ratio ranged between 1.67 and 2.23 with duplication and between 1.29 and 1.74 without duplication according to the results of Southern blot analysis. However, some patients exhibited overlapping signal intensity in the duplication and non-duplication ranges. Thus, these three methods each has its own advantages and disadvantages in regard to detecting duplication.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗