Search PubMed⌕ Search

Biomedical subjects

M Uchino

Publications and source records attributed to M Uchino.

At least 109 records · Page 6Linked to original sources
PubMed1997

Down regulation of a harmful variant protein by replacement of its normal protein.

To compensate for the hypoprotein and hypoalbuminemia of familial amyloidotic polyneuropathy (FAP) patients, 800 ml of fresh frozen plasma (FFP) was intravenously administered and change in total and variant transthyretin (TTR) levels were measured in the plasma. After injection of FFP, total plasma TTR levels were elevated and variant TTR levels decreased from 24 to 48 h, accompanied by an elevation of plasma total protein, albumin levels and TTR levels. To elucidate the mechanism of this phenomenon, a large amount of purified normal TTR from normal human plasma was intravenously injected in mice and FAP patients. By intravenous injection of 3 mg of the purified TTR to C57Black6, the expression of TTR mRNA decreased from 6 to 24 h post injection, and gradually increased up to 48 h post injection. After injecting 400 mg of normal TTR in each of 3 FAP patients, total plasma TTR levels were elevated and variant TTR levels decreased significantly from 24 to 48 h. These results suggested that down regulation of the harmful protein by replacement of its normal form of the protein occurred by this method. This phenomenon should be applied as the basis for one of the useful methods for decreasing the harmful proteins in the circulation.

Adult↗
PubMed1997

The reduction of androgen receptor mRNA in motoneurons of X-linked spinal and bulbar muscular atrophy.

We examined the expression level of androgen receptor (AR) messenger RNA (mRNA) in the motoneurons from patients with X-linked spinal and bulbar muscular atrophy (SBMA) and amyotrophic lateral sclerosis (ALS) using in situ hybridization. Although AR mRNA was detected in motoneurons from the SBMA patient, the expression level was lower than that from the patients with ALS, despite similar loss of motoneurons. The expression level of AR mRNA in the dorsal nucleus of Clarke from the patient with SBMA was similar to that in the patients with ALS, suggesting that the qualities of the mRNA were similar in each spinal cord sample and that AR mRNA was uniquely reduced in the motoneurons of the SBMA patient. Decreased levels of AR mRNA may be involved in the pathogenesis of SBMA resulting in degeneration of motoneurons.

Amyotrophic Lateral Sclerosis↗
PubMed1997

Specific attenuation of the pressure-induced contraction of rat cerebral artery by herbimycin A.

In order to determine whether protein tyrosine kinase mechanisms are involved in pressure-induced contraction, we compared effects of three structurally unrelated tyrosine kinase inhibitors and orthovanadate, a tyrosine phosphatase inhibitor, on the pressure-induced contraction of the posterior cerebral artery isolated from rats. The change in vessel diameter was continuously measured with a width analyzer. Herbimycin A inhibited the pressure-induced contraction, while it only slightly inhibited contractions produced by potassium chloride or 9,11-dideoxy-11alpha,9alpha-epoxymethano prostaglandin F2alpha (U46619). Genistein inhibited not only the pressure-induced contraction but also the U46619-induced one. Tyrphostin 23 significantly attenuated contractions in response to three different stimuli, i.e., pressure, potassium chloride and U46619. Orthovanadate potentiated the pressure-induced contraction. These results suggest that herbimycin A is a specific and potent inhibitor of the pressure-induced contraction and that a protein tyrosine kinase mechanism may play an important role in the genesis of the pressure-induced contraction of the rat cerebral artery.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1997

Oxidative stress is found in amyloid deposits in systemic amyloidosis.

Oxidative stress in human amyloid deposits from patients with systemic amyloidosis, such as familial amyloidotic polyneuropathy (FAP), primary amyloidosis, and secondary amyloidosis, was examined immunohistochemically by means of an affinity purified anti-hydroxynonenal (HNE) antibody to HNE, a marker of lipid peroxidation. Furthermore, the levels of thiobarbituric acid reactive substances (TBARS), which is another marker of lipid peroxidation, and the levels of protein carbonyl, a maker of protein modifications by free radicals, were determined in FAP patients and healthy controls. Affinity purified anti-HNE antibody reacted with amyloid deposits in all types of amyloid tissues examined. Significantly higher levels of TBARS and protein carbonyl were found in amyloid rich tissues of FAP patients compared with those in the control subjects. These results verify that lipid peroxidation via free radical injury occurs in amyloid deposits in systemic amyloidosis. The protein modifying properties of free radicals increase the likelihood that they play an important role in the amyloid formation process.

Adult↗
PubMed1997

Role of nitric oxide in the cerebellar degeneration during methylmercury intoxication.

To investigate the role of nitric oxide in the cerebellar degeneration during methylmercury intoxication, interaction of the change in nitric oxide synthase activity and degeneration of the granular layer neurons was examined in rats after methylmercury administration. Both reduced nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase and anti-nitric oxide synthase antibody staining, and measurement of glutamate, and nitrite and nitrate levels in the cerebrospinal fluid were performed after oral administration of 5 mg/kg of methylmercury for 12 days. Nitric oxide synthase activity in the cerebellum was also assayed by monitoring the conversion of arginine to citrulline. Methylmercury levels in the blood and the cerebellum gradually increased up to day 13 after the initial methylmercury administration, and neurological disturbances, such as hindleg crossing and abnormal gait, were observed from day 17 after administration. Although a significant decrease in the number of granular layer neurons was recognized at day 84, no such decrease either in NADPH-diaphorase or anti-nitric oxide synthase antibody positive neurons was seen. Glutamate levels in the cerebrospinal fluid transiently increased at day 9 and finally decreased at day 84. Also a transient increase in both nitrite and nitrate levels in the cerebrospinal fluid and nitric oxide synthase activity in the cerebellum was seen prior to the start of degeneration of the granular layer neurons. These results suggest that nitric oxide may play an important role in the degeneration process of the granular layer neurons during methylmercury intoxication.

Animals↗
PubMed1997

Oculopharyngeal muscular dystrophy in Japan.

Oculopharyngeal muscular dystrophy (OPMD) in the European population has been frequently diagnosed, but except for one black family, the occurrence in other ethnic groups is uncertain. We identified two unrelated OPMD Japanese families, including 34 affected individuals. Major clinical manifestations were bilateral ptosis and dysphagia starting after age 40. Histologic studies of limb muscles revealed mild myogenic changes, occasional rimmed vacuoles, and small angulated fibers. By contrast, cricopharyngeal muscle showed a marked loss of fibers and massive proliferation of connective tissue. Intranuclear tubulofilamentous inclusions (ITFI) of 8.5 nm outer diameter were observed in 2-5% of the nuclei in four different biopsied muscles. One patient with recurrent aspirations underwent successful cricopharyngeal myotomy. Aerodynamic examination was useful to evaluate velopharyngeal closure function. Our investigations revealed that OPMD is a geographically widespread disorder, and ITFI may be the specific morphologic hallmark.

Biopsy↗
PubMed1997

Ocular manifestations of familial amyloidotic polyneuropathy type I: long-term follow up.

AIMS: To obtain precise information on ocular manifestations of familial amyloidotic polyneuropathy (FAP) type I, the incidence of five main ocular manifestations--abnormal conjunctival vessels (ACV), keratoconjunctivitis sicca (KCS), pupillary abnormality, vitreous opacity, and glaucoma, were compared through long term follow up. METHODS: Ocular examinations were performed in 37 FAP type I patients (Met30) from once to 12 times over a period of 1 to 12 years and 7 months. RESULTS: The following incidences were observed on initial examination of each patient with FAP: ACV in 75.5%, pupillary abnormalities in 43.2%, KCS in 40.5%, glaucoma in 5.4%, and vitreous opacity in 5.4%. All ocular manifestations increased with the progression of FAP, and the incidence of ACV reached 100% during follow up: this may be helpful in the diagnosis of FAP. CONCLUSION: Since no precise statistical ocular study on FAP with long term follow up has been performed, this report may provide important information to help elucidate the mechanism of the amyloid distributing process in the amyloid targeted organs of FAP and to provide the natural course of ocular manifestations of FAP.

Adult↗
PubMed1997

Spontaneous dissection associated with proximal vertebral artery anomaly.

A 47-year-old man was admitted because of acute lateral medullary syndrome with severe posterior cervical pain. Cerebral angiography was performed three hours after the onset, which demonstrated that two arteries branched separately from the right subclavian artery, ran upward and formed a single right vertebral artery (VA). One of the two arteries showed both stenosis and luminal dilatation. We thought the structure of these arteries was proximal vertebral artery anomaly and diagnosed him as having dissection of the vertebral artery. We consider that the proximal vertebral anomaly may be a risk for spontaneous VA dissection.

Acute Disease↗
PubMed1997

[Cerebellar atrophy in Minamata disease: comparison with spino-cerebellar degeneration on MR images].

We evaluated atrophic patterns of the cerebellar vermis in seven patients with Minamata disease (MD) and nine patients with spino-cerebellar degeneration (SCD) on MR images. Twenty-five control subjects were also examined. The cerebellar vermis was divided into superior, middle, and inferior parts by the primary fissure and the prepyramidal fissure on the median sagittal T1-weighted MR image. The length and area of each part were measured. In the patients with SCD, there were no significant differences in the degree of atrophy among the three parts. However, MR images of the patients with MD showed more severe atrophy in the middle and inferior parts than in the superior part. Atrophy of the superior part was less frequently observed in MD patients.

Adult↗
PubMed1997

Single-photon emission CT findings in acute Japanese encephalitis.

PURPOSE: To determine the usefulness of single-photon emission CT (SPECT) in the diagnosis of acute Japanese encephalitis (JE). METHODS: We examined 10 patients (six men and four women; mean age, 69 years) with viral encephalitis. We divided the cases into two groups: the JE group (n = 4) and the non-JE group (n = 6; two with herpes simplex encephalitis and four with encephalitis of unknown origin). All cases were investigated with 99mTc-hexamethylpropyleneamine oxime (HMPAO) SPECT within 15 days after the onset of symptoms. Two patients in the JE group were also examinated by SPECT at a later stage. In all cases MR imaging was performed after the SPECT study. RESULTS: In the acute stage, all patients in the JE group showed a marked increase of HMPAO uptake that matched the hyperintense area observed on MR images in the thalami and putamina bilaterally. Follow-up SPECT studies of two patients with JE revealed a decrease of HMPAO deposition in the areas of high uptake. None of the patients in the non-JE group had an increased accumulation of HMPAO in the thalami or the putamina. CONCLUSIONS: SPECT is helpful in differentiating JE from herpes simplex encephalitis and other types of encephalitis. SPECT may be useful as a diagnostic tool in the early stages of JE.

Acute Disease↗
PubMed1997

[Brain embolism associated with atrial septal aneurysm].

We studied the clinical significance of atrial septal aneurysm on brain embolism. Of two-hundred twenty-eight consecutive ischemic stroke patients, 128 cases were performed transesophageal echocardiography to find cardiac lesions that could be embolic sources. Three cases were diagnosed as having atrial septal aneurysm with right-to-left shunt demonstrated by contrast echocardiography under Valsalva maneuver. These cases were all diagnosed as brain embolism from clinical courses and findings from brain CT scan, and cerebral angiography. Neurosonologic study, 24 hours Holter ECG, and transthoracic echocardiography did not reveal any other embolic sources. Paradoxical embolic mechanism is supposed to have occurred in these cases. Atrial septal aneurysm often coexists with right-to-left shunt and is clinically significant as a finding suggesting paradoxical embolism.

Aged↗
PubMed1997

[A case of vertebral artery dissection with lateral inferior pontine syndrome and lateral medullary syndrome].

A 55-years-old woman had left neck pain and headache, dizziness, left Horner's sign, left abducens palsy, diplopia, left peripheral facial palsy, left loss of hearing, left tinnitus, left paralysis of vocal cord and soft palate, dysphagia, left limb ataxia, truncal ataxia, disturbance of temperature and pain sensation over Th10 on the right involving the right face. Left vertebral angiography revealed tapering occlusion of the left vertebral artery. Right vertebral angiography showed normal angiogram of the basilar artery and bilateral anterior inferior cerebellar arteries. MRI disclosed infarcts in the left lateral inferior pons, left lateral medulla, and cerebellum of territories in the anterior inferior cerebellar artery and posterior inferior cerebellar artery. T2 weighted image showed septum (intimal flap) in the left vertebral artery. This is the very rare case of lateral inferior pontine syndrome and lateral medullary syndrome due to the vertebral artery dissection.

Aortic Dissection↗
PubMed1997

Duplex carotid sonography in distinguishing acute unilateral atherothrombotic from cardioembolic carotid artery occlusion.

PURPOSE: To distinguish between acute complete unilateral cardioembolic and atherothrombotic internal carotid artery (ICA) occlusion by using duplex carotid sonography. METHODS: We studied 11 patients with cardioembolic ICA occlusion (CE group), 32 patients with atherothrombotic ICA occlusion (AT group), and 25 patients with normal angiographic findings (control group). We obtained B-mode scans and measured the end-diastolic flow velocity (EDV) in both common carotid arteries within 3 days of the onset of symptoms. Side-to-side ratios of EDV (ED ratio) were calculated by dividing the flow velocity on the unaffected side by that on the affected side. RESULTS: In the AT group, the proximal ICA was full, with a large area of heterogeneous and partially calcified plaque, and the EDV (10.9 +/- 6.1 cm/s) was significantly lower than that in the control group (20.3 +/- 6.0 cm/s). The ED ratio was greater than 1.4 in all but one patient. In three patients in the CE group, B-mode scans showed a mobile, echogenic intravascular structure in the proximal ICA. The EDV (1.8 +/- 3.4 cm/s) was significantly lower than that in the control and AT groups. The ED ratio was greater than 1.4 in all cases. CONCLUSION: We conclude that B-mode scans and the EDV in the common carotid artery can help to distinguish between acute cardioembolic and atherothrombotic ICA occlusion.

Aged↗
PubMed1997

[Cerebral embolism due to lone atrial septal aneurysm].

A 71-year-old man was admitted to our hospital because of headache and left hemiparesis. Brain CT scan showed hemorrhagic infarction of the right frontal lobe. Intravenous digital subtraction angiography revealed no occlusion of cerebral arteries. No arrhythmias were observed by the holter ECG. Transthoracic echocardiography showed no abnormalities. Anticoagulation therapy (heparin and warfarin) was started under the diagnosis of cerebral embolism without definite embolic source and there was no recurrence during following four years. Transesophageal echocardiography showed an atrial septal aneurysm (ASA) without patent foramen ovale. A potential cause of cerebral embolism due to atrial septal aneurysm is paradoxical embolization through an interatrial shunt (patent foramen ovale). It was speculated that ASA was a direct source of thrombus formation in this case (lone ASA). Transesophageal echocardiography should be performed to find atrial septal aneurysm in patients with cryptogenic stroke, especially embolic stroke without definite embolic sources.

Aged↗
PubMed1997

[Single-fiber polymerase chain reaction for detection of mutant mitochondrial DNA].

Single-fiber PCR amplifies mitochondrial DNA (mtDNA) in single muscle fiber isolated from cross frozen section. The PCR products are digested with a restriction enzyme to distinguish mutant mtDNA from wild-type mtDNA. The proportion of mutant mtDNA is higher in ragged-red fiber (RRF) than in non-RRF in mitochondrial encephalomyopathies with mutations of mtDNA. This method may be applied to evaluate amount of mtDNA and mRNA in single muscle fiber, and become a powerful tool to elucidate the pathogenetic mechanism in mitochondrial encephalomyopathies.

DNA, Mitochondrial↗