Biomedical subjects

Makoto Uchino

Publications and source records attributed to Makoto Uchino.

At least 19 recordsLinked to original sources

PubMed2006

Microembolic signals within 24 hours of stroke onset and diffusion-weighted MRI abnormalities.

BACKGROUND: The clinical relevance of the microembolic signals (MES) detected by transcranial Doppler sonography (TCD) in acute stroke remains unclear. In a prospective study the authors analyzed the relationship between MES and the findings on diffusion-weighted magnetic resonance imaging (DWI) in acute stroke patients. METHODS: We performed TCD for a period of 30 min to detect MES in patients within 24 h of stroke onset, and DWI was done within the initial 7 days. MES were assessed from Doppler waves obtained from the middle cerebral artery contralateral to the side of the neurological deficits. The acute ischemic lesions observed on DWI were classified by their diameter (small, medium or large) and by their site (cortical, superficial perforator territory, internal borderzone or deep perforator territory). RESULTS: We obtained Doppler waves from 39 vessels in 37 patients; 2 patients had bilateral deficits. MES were detected in 12 vessels (MES-positive group) and not detected in 27 vessels (MES-negative group). No significant differences in clinical features were observed between the 2 groups. The number of small lesions was significantly higher in the MES-positive group than in the MES-negative group (p = 0.02). The numbers of cortical and superficial perforator infarcts were significantly higher in the MES-positive group than in the MES-negative group (p = 0.002 and 0.02, respectively). CONCLUSION: In acute ischemic stroke, MES detected by TCD in the acute phase may produce small cortical and subcortical lesions found on DWI.

Acute Disease↗

PubMed2006

A transgenic rat with the human ATTR V30M: a novel tool for analyses of ATTR metabolisms.

Amyloidogenic transthyretin (ATTR) is the pathogenic protein of familial amyloidotic polyneuropathy (FAP). To establish a tool for analyses of ATTR metabolisms including after liver transplantations, we developed a transgenic rat model expressing human ATTR V30M and confirmed expressions of human ATTR V30M in various tissues. Mass spectrometry for purified TTR revealed that rat intrinsic TTR and human ATTR V30M formed tetramers. Congo red staining and immunohistochemistry revealed that nonfibrillar deposits of human ATTR V30M, but not amyloid deposits, were detected in the gastrointestinal tracts of the transgenic rats. At 24h after liver transplantation, serum human ATTR V30M levels in transgenic rats that received livers from normal rats became lower than detectable levels. These results thus suggest that this transgenic rat may be a useful animal model which analyzes the metabolism of human ATTR V30M including liver transplantation studies.

Amyloid Neuropathies, Familial↗

PubMed2006

FK506 inhibits murine AA amyloidosis: possible involvement of T cells in amyloidogenesis.

OBJECTIVE: To determine the possibility that T cells represent a potential target for therapy in AA amyloidosis. METHODS: AA amyloidosis was induced in C3H/HeN mice by concomitant administration of AgNO3 and amyloid-enhancing factor (AEF). Mice injected with AgNO3 and AEF received intraperitoneal injections of FK506 (2-200 microg/day). The degree of splenic amyloid deposition was determined by Congo red staining. Serum amyloid A (SAA), interleukin 1beta (IL-1beta), IL-6, and tumor necrosis factor-a concentrations were measured by ELISA. AA amyloidosis was also induced in ICR mice by injection of Freund's complete adjuvant (FCA) and Mycobacterium butyricum without AEF. ICR mice injected with FCA and M. butyricum also received intraperitoneal injections of FK506 (200 microg/day) to eliminate the possibility that FK506 action might depend upon AEF activity in the amyloid formation. Amyloid deposition was also induced with and without AEF in severe combined immunodeficient (SCID) mice and nude mice to clarify the role of T cells in the mechanism of amyloid formation in AA amyloidosis. RESULTS: FK506 treatment significantly reduced the amount of amyloid deposition and incidence of amyloidosis without reducing serum SAA and proinflammatory cytokine levels in the murine AA amyloidosis models with and without AEF. SCID mice and nude mice showed resistance to development of AA amyloidosis. CONCLUSION: Our findings may provide a new therapeutic strategy for amyloidosis. The results suggested that T cells may play an important role in the mechanism of amyloid formation in AA amyloidosis.

Amyloidosis↗

PubMed2006

Efficacy of edaravone in cardioembolic stroke.

OBJECTIVE: We investigated the efficacy of edaravone in patients with cardioembolic stroke. METHODS: Cardioembolic stroke patients were treated with drip intravenous infusion of edaravone (ED group, n=141) for 7 days, and were retrospectively compared with a historical-controlled cohort of similar patients (control group, n=114). RESULTS: Early improvement (between day 0 and day 10), defined as change in National Institutes of Health Stroke Scale (NIHSS), was seen more frequently in mild patients (NIHSS on admission < or = 7) among the ED group than in the control group (change in NIHSS +2 vs. -2, respectively, p=0.013). Similar efficacy was not seen in the moderate to severe (NIHSS >7) patients. Independent patients (modified Rankin Scale < or = 2) 6 months after the onset were likely to be less frequent in the ED than the control group (28% versus 41%; p=0.066). Other clinical outcomes in the ED group were not significantly different from those in the control group. CONCLUSION: The results suggest that edaravone may only be effective in mild patients with cardioembolic stroke.

Aged↗

PubMed2006

Rotational vertigo associated with parietal cortical infarction.

A 65-year-old woman experienced sudden positional vertigo with rightward, horizontal nystagmus that resolved within days. MRI revealed a left parietal lobe infarction involving the supramarginal gyrus. The patient experienced a transient recurrence of vertigo after 7 days but MRI failed to reveal the presence of any new lesions; furthermore, the patient's EEG was normal. We suggest that this patient's vertigo was due to her parietal cortical infarction.

Aged↗

PubMed2006

Aging and transthyretin-related amyloidosis: pathologic examinations in pulmonary amyloidosis.

Although aging is closely related with the onset of senile systemic amyloidosis (SSA) caused by wild-type transthyretin (TTR), the effect of aging on amyloid formation has remained unclear in familial amyloidotic polyneuropathy (FAP), caused by variant- and wild-type TTR. The aim of this study was to elucidate the effects of aging and/or other factors in FAP on amyloid formation in the lung, one of the most important target organs of amyloid deposition in SSA. Pulmonary amyloid distribution was determined using 19 autopsied lung samples from patients with FAP amyloidogenic TTR (ATTR) V30M, the most common type of FAP. Amyloid deposition was observed around the walls of the bronchi/ bronchioles, the pulmonary arteries, and the pulmonary veins, while no amyloid deposits could be found around the lymphatics. In addition, amyloid deposition in the alveolar regions was a characteristic finding in aged patients with FAP ATTR V30M (average ages of the patients with amyloid positive vs. negative: 50.55 +/- 8.75 vs. 39.75 +/- 4.17 years old, p < 0.005), similar to the finding in one SSA patient. These results suggest that aging could play an important role in the progression of pulmonary amyloid formation in FAP ATTR V30M.

Adult↗

PubMed2006

[A case report of streptococcus oralis meningitis after dental manipulation].

A 75-year-old man was admitted to our hospital because of high fever and disturbance of consciousness 4 days after dental treatment including scaling, irrigation, and oral antibiotic for dental caries without gingivitis. A lumber puncture revealed cloudy cerebrospinal fluid (CSF): it contained 984 leukocytes/mm3, 680 mg/dl of protein, 5 mg/dl of glucose (blood sugar 233 mg/dl), and Streptococcus oralis, one of common microorganisms on the gingival, was isolated from the CSF. He was successfully treated with intravenous antibiotics. The authors believe this patient's meningitis developed as a result of bacteremia after the dental scaling in the present case.

Aged↗

PubMed2006

[Seizure-induced transient brain edema in the medial temporal lobe].

We reported a patient with sudden onset seizure resulting in prolonged amnesia. MRI revealed a T2 high signal lesion with swelling in the right medial temporal lobe. Because the MRI lesion remained to be the same in size for two months, biopsy specimens were obtained under informed consent to rule out the brain tumor. Based on histological findings showing brain edema without specific abnormal findings (malignancy, inflammation etc), we concluded that the temporal lesion was the edema induced by the seizure attack. In Japan, many papers on non-herpetic acute limbic encephalitis (NHALE) have recently been published. In their reports, seizures were frequently observed as a preceding symptom; moreover, clinical courses and MRI findings are similar to those of seizure-induced brain edema. The secondary brain edema induced by the seizure must be considered in patients with NHALE and other CNS disorders, especially if the patient has a history of the recent seizure.

Adult↗

PubMed2006

[Decompressive craniectomy for ischemic stroke].

We analysed retrospectively 15 consecutive patients with cerebral infarction undergoing decompressive craniectomy. Ninety-three percent of patients survived, and 53% of them were partially dependent (Barthel Index > 0). We defined the partially dependent patients as good outcome group, and totally dependent as poor outcome group. In good outcome group, compared with poor outcome group, there are more frequent left hemispheric lesion (50%: 0%, p = 0.029), and pre-operative JCS < or = II-30 (62.5%: 14.3%, p = 0.057). Although many patients were severely disabled, 79% of the patients and their family answered that having operation was correct choice. All the patients in good outcome group acquired the ability of oral feeding and communication skill. 87.5% of the patient in good outcome group was satisfied with the outcome. Based on these results, we emphasized that comprehensive evaluations, including satisfaction scale and QOL assessment necessary to decide the indication of decompressive craniectomy for ischemic stroke.

Activities of Daily Living↗

PubMed2006

[Early seizures after acute ischemic stroke].

In order to determine predictive factors of early seizures (ES) after acute stroke and to estimate prognosis, we retrospectively examined clinical data of 1,743 consecutive patients with acute ischemic stroke. The subjects were divided into two groups; an ES group (19 patients) and a non-ES group (1,724 patients). Multivariate statistical analysis revealed that the NIH-Stroke Scale score on admission (/10, OR, 1.1: 95% CI 1.04 to 1.13) and positive past history of cerebrovascular disease or brain injury (OR, 3.85: 95% CI 1.49 to 9.95) are significant factors to predict ES. There was no significant difference in the outcome between the two groups. A recurrence of seizures, after follow up for 4 to 40 months, was observed only in one patient with a history of ES.

Acute Disease↗

PubMed2006

[Two cases of cavernous sinus dural arteriovenous fistula presenting headache as the one and only initial symptom].

We report 2 cases with cavernous sinus dural arteriovenous fistula (C-dAVF) presenting with headache as an initial symptom. A 70-year-old woman complained of acute persistent headache in the right temporal region. Another 74-year-old woman suffered from sudden and severe headache, developing from right-sided temporal throbbing to bilateral headache. Her condition was also complicated with cranial nerve deficits. These two patients were finally diagnosed as having C-dAVF based on the results of magnetic resonance angiography and cerebral angiography. It was difficult to make rapid diagnosis of C-dAVF in our patients, because they presented with headache alone but no typical symptoms of C-dAVF, such as proptosis, conjunctival injection or orbital bruit. C-dAVF should be considered as an important differential diagnosis in patients with headache.

Aged↗

PubMed2005

Leber's hereditary optic neuropathy with dystonia in a Japanese family.

We investigated a Japanese family with generalized dystonia attributed to striatal degeneration, which occurred in childhood, and late-onset optic neuropathy. We determined the entire nucleotide sequence of mitochondrial DNA (mtDNA) from the proband and compared our findings with the 2001 Revised Cambridge Reference Sequence. The mtDNA of the proband showed a total of 42 nucleotide changes. We identified two A3203G and G14459A mutations, which were completely absent in a population of 200 healthy Japanese, by estimating the frequency of each nucleotide change. The nucleotide G14459A mutation occurs in NADH dehydrogenase subunit 6, and has been suggested previously as the disease-causing mutation in Hispanic, African-American and Caucasian families of Leber's hereditary optic neuropathy (LHON) and/or dystonia. The significance of the A3203G mutation remains unknown. To our knowledge, this is the first case of LHON with dystonia that revealed a mtDNA mutation in a Japanese family.

Adult↗

PubMed2005

Presence of early ischemic changes on computed tomography depends on severity and the duration of hypoperfusion: a single photon emission-computed tomographic study.

BACKGROUND AND PURPOSE: To evaluate the clinical significance of early ischemic change (EIC) on computed tomography (CT), pertinent factors that contribute to the appearance of EIC. METHODS: Both CT and technetium-99m hexamethylpropylene amine oxime were performed on a total of 53 patients (34 men, 19 women, mean 69.7 years old) with acute embolic stroke within 6 hours of onset. Patients were excluded if they showed definite clinical recovery or were administered thrombolytic agents. EIC was evaluated using Alberta Stroke Program Early CT Score (ASPECTS). Residual cerebral blood flow (CBF) was determined on SPECT. Variables that were considered pertinent were patients' age, gender, neurological severity, symptom duration, and residual CBF. Using significant pertinent factors for EIC, separate analyses of brain swelling without hypoattenuation and parenchymal hypoattenuation were performed. RESULTS: Patients with EIC (n=37) showed severe neurological deficits, a longer duration and severe hypoperfusion. A positive correlation was observed between ASPECTS and residual CBF (P=0.002; Kruskal-Wallis test). A logistic-regression analysis revealed that both symptom duration (r=0.024, P=0.006) and severity of hypoperfusion (r= -12.167, P=0.006) are independent factors related to EIC. Symptom duration and residual CBF were significantly different among patients with parenchymal hypoattenuation (n=32), brain swelling without hypoattenuation (n=5), and no EIC (P=0.018 and P=0.001, respectively; one-way ANOVA). CONCLUSIONS: The presence of EIC is determined by the duration and the degree of hypoperfusion. This finding supports the hypothesis that tissue damage may be evaluated by a combination of onset time and the presence of EIC.

Adult↗

PubMed2005

CADASIL with NOTCH3 S180C presenting anticipation of onset age and hallucinations.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited disease leading to strokes and vascular dementia. The average age of onset for stroke is 45 years with a range of about 30 to 70 years. We describe a Japanese CADASIL family showing S180C in the exon 4 of NOTCH3, presenting an anticipation of the onset age for stroke. MRI demonstrated a similar extent of white matter involvement in younger and older individuals, supporting the presence of anticipation. In addition, hallucinations in 71% of affected patients, and delusions in 57% were also described. Our findings in this family suggest that a specific NOTCH3 mutation was related to unique clinical features, although such correlations have seldom been encountered in CADASIL.

Adult↗

PubMed2005

Staphylococcus cohnii as a cause of multiple brain abscesses in Weber-Christian disease.

We report a patient with multiple brain abscesses due to Staphylococcus cohnii. While these brain abscesses markedly responded to the antibiotics, this patient was subsequently suffered from subcutaneous inflammatory nodules in the adipose tissue, which diagnosed him as having Weber-Christian disease (WCD). This is the first report that subcutaneous inflammatory nodules in the adipose tissue, which lead the diagnosis of WCD, followed multiple brain abscesses. To our knowledge, S. cohnii has not yet been reported to cause multiple brain abscesses in humans. Although the etiology of WCD is unknown, an immune mechanism has been implicated in the pathogenesis. Therefore, we should notice that patients with WCD could be immunocompromised hosts with a higher risk to suffer from severe opportunistic infections.

Adipose Tissue↗

PubMed2005

Hyperacute diffusion-weighted imaging abnormalities in transient ischemic attack patients signify irreversible ischemic infarction.

BACKGROUND: To characterize the frequency and clinical features of diffusion-weighted imaging (DWI) abnormalities in the hyperacute phase of transient ischemic attacks (TIAs). METHODS: We performed DWI in 21 consecutive patients with TIA (mean age 64 years; 17 men and 4 women) during both the hyperacute phase (within 6 h after onset) and subacute phase (within 2-9 days after onset). RESULTS: DWI abnormalities were present in the hyperacute phase in 11 patients (positive group) and absent in the other 10 patients (negative group). These groups could not be differentiated based on the clinical characteristics. In the subacute phase, all 11 patients from the positive group had abnormalities on MRI including T2-weighted and fluid attenuation inversion recovery images as well as DWI, with lesions being located in regions similar to those observed in the hyperacute phase. Of the 10 patients in the negative group, new DWI abnormalities were noted in 2 during the subacute phase. CONCLUSIONS: Approximately half of TIA patients in whom MRI was performed in the hyperacute phase had DWI abnormalities, all of which persisted in the subacute phase. The findings suggest that essentially all hyperacute DWI abnormalities in TIA patients may indicate irreversibility and signify the presence of brain infarction.

Adult↗

PubMed2005

Effective repetitive dystrophin gene transfer into skeletal muscle of adult mdx mice using a helper-dependent adenovirus vector expressing the coxsackievirus and adenovirus receptor (CAR) and dystrophin.

BACKGROUND: The helper-dependent adenovirus (HDAd) vector is less immunogenic and has a larger cloning capacity of up to 37 kb enough to carry the full-length dystrophin cDNA. However, high and long-term expression of dystrophin transduced to mature muscle still remains difficult. One of the main reasons for this is that the expression of the coxsackievirus and adenovirus receptor (CAR) is very low in mature muscle. METHODS: We have constructed two different HDAd vectors. One contains the LacZ and the murine full-length dystrophin expression cassette (HDAdLacZ-dys), and the other is a new, improved vector containing the CAR and the dystrophin expression cassette (HDAdCAR-dys). RESULTS: We initially demonstrated high dystrophin expression and prevention of the dystrophic pathology in mdx muscle injected during the neonatal phase with HDAdLacZ-dys. Furthermore, we demonstrated that repeated injections of HDAdCAR-dys into mature muscle led to approximately nine times greater dystrophin-positive fibers in number than a single injection, thereby recovering the expression of dystrophin-associated proteins. This data has also shown that HDAdCAR-dys enabled administration of adenovirus (Ad) vector to the host with pre-existing immunity to the same serotype of Ad. CONCLUSIONS: Repetitive injections of the HDAd vector containing the CAR and the dystrophin expression cassette could improve the efficiency of subsequent dystrophin gene transfer to mature mdx muscle. This result suggests that our new HDAd vector will provide a novel gene therapy strategy for Duchenne muscular dystrophy, raising the prospects for gene therapy of other hereditary myopathies.

Adenoviridae↗

PubMed2005

Muscular amyloid angiopathy with amyloidgenic transthyretin Ser50Ile and Tyr114Cys.

Among patients with familial amyloid polyneuropathy (FAP), those with transthyretin Val30Met mainly show distally predominant weakness and atrophy, whereas some FAP patients, including those with transthyretin Ser50Ile and Tyr114Cys, show muscle weakness and atrophy that is dominant proximally, simulating myopathy. To clarify the cause of proximally dominant muscular atrophy in patients with FAP transthyretin Ser50Ile and Tyr114Cys, we investigated the distinctive features of muscle specimens of patients with FAP, 3 of who had Val30Met, 2 Ser50Ile, and 2 Tyr114Cys transthyretin. All specimens showed transthyretin amyloid around blood vessels and perimysium, and neurogenic denervation patterns. The amount of amyloid around the vessels was much greater in patients with FAP Ser50Ile and Tyr114Cys than in Val30Met patients. Muscular amyloid angiopathy may contribute to motor nerve injury that, in turn, may lead to amyotropic changes in patients with FAP Ser50Ile and Tyr114Cys.

Adult↗