Biomedical subjects
Publications and source records attributed to Y Shiga.
We measured the CSF tau protein levels in 26 patients with Guillain-Barré syndrome. The levels of the poor outcome group (Hughes grade at 6 months was between II and VI, n = 6) were higher than those of the good outcome group (0 or I, n = 20) (p < 0.0005). The higher levels of CSF tau may reflect axonal degeneration and could predict a poor clinical outcome in Guillain-Barré syndrome.
Chromosome 16q22.1-linked autosomal dominant cerebellar ataxia (16q-ADCA) is strongly associated with a substitution in the puratrophin-1 gene. This locus overlaps with spinocerebellar ataxia type 4 (SCA4) which shows ataxia with prominent sensory axonal neuropathy. We found that 16q-ADCA is a common ADCA subtype in the Tohoku District of Japan. The clinical feature of Japanese 16q-ADCA is characterized as late-onset pure cerebellar ataxia.
This study investigates the relation between the serological status of NMO (neuromyelitis optica)-IgG and the clinical and MRI features in Japanese patients with multiple sclerosis. Serum NMO-IgG was tested in 35 Japanese patients diagnosed with multiple sclerosis, including 19 with the optic-spinal form of multiple sclerosis (OSMS), three with the spinal form of multiple sclerosis (SMS), and 13 with the conventional form of multiple sclerosis (CMS), which affects the brain. NMO-IgG was detected in 14 patients, 12 with OSMS and 2 with CMS. In these patients, longitudinally extensive (> 3 vertebral segments) spinal cord lesions (93% v 57%) and permanent, complete blindness (no perception of light) in at least one eye (50% v 0%) were the noticeable features as compared with NMO-IgG-negative OSMS. The two patients having CMS with NMO-IgG had unusual brain lesions, but in other respects had features suggesting OSMS. NMO-IgG was detected in more than half the number of patients with OSMS and in some patients with CMS. This newly discovered serum autoantibody was markedly associated with longitudinally extensive spinal cord lesions and with complete blindness, suggesting severe optic-spinal disease.
Reactivation of chronic hepatitis B virus (HBV) infection in patients undergoing chemotherapy is well-documented, but reactivation during imatinib mesylate treatment has not been reported. This study reports a 54-year-old man, without prior liver dysfunction but with chronic HBV infection, in whom fatal HBV reactivation occurred during treatment of chronic myeloid leukemia (CML) with imatinib mesylate. He developed fulminant hepatitis followed by marked elevation of HBV DNA polymerase, probably from the lymphocytopenic and immunosuppressive status induced by imatinib mesylate. Imatinib mesylate is widely used to treat CML patients. Although therapy with imatinib mesylate is generally well tolerated, the case presented here suggests that viral reactivation should be considered, even when using imatinib mesylate to treat CML.
BACKGROUND: No method for the clinical diagnosis of MM2-type sporadic Creutzfeldt-Jakob disease (sCJD) has been established except for pathologic examination. OBJECTIVE: To identify a reliable marker for the clinical diagnosis of MM2-type sCJD. METHODS: CSF, EEG, and neuroimaging studies were performed in eight patients with MM2-type sCJD confirmed by neuropathologic, genetic, and western blot analyses. RESULTS: The eight cases were pathologically classified into the cortical (n = 2), thalamic (n = 5), and combined (corticothalamic) (n = 1) forms. The cortical form was characterized by late-onset, slowly progressive dementia, cortical hyperintensity signals on diffusion-weighted imaging (DWI) of brain, and elevated levels of CSF 14-3-3 protein. The thalamic form showed various neurologic manifestations including dementia, ataxia, and pyramidal and extrapyramidal signs with onset at various ages and relatively long disease duration. Characteristic EEG and MRI abnormalities were almost absent. However, all four patients examined with cerebral blood flow (CBF) study using SPECT showed reduction of the CBF in the thalamus as well as the cerebral cortex. The combined form had features of both the cortical and the thalamic forms, showing cortical hyperintensity signals on DWI and hypometabolism of the thalamus on [18F]2-fluoro-2-deoxy-d-glucose PET. CONCLUSION: For the clinical diagnosis of MM2-type sporadic Creutzfeldt-Jakob disease, cortical hyperintensity signals on diffusion-weighted MRI are useful for the cortical form and thalamic hypoperfusion or hypometabolism on cerebral blood flow SPECT or [18F]2-fluoro-2-deoxy-d-glucose PET for the thalamic form.
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OBJECTIVE: To evaluate the usefulness of diffusion-weighted MRI (DWI) for the early diagnosis of Creutzfeldt-Jakob disease (CJD). METHODS: Thirty-six consecutive patients (age 56 to 82 years) were enrolled, and 26 were examined by DWI. Nine were definite based on the World Health Organization criteria, and 27 were probable. The percentages of DWI abnormalities, periodic sharp wave complexes (PSWCs) on the EEG, detection of CSF 14-3-3 protein, and increase of CSF neuron-specific enolase (>25 ng/mL) on the first examination were compared. For DWI, 32 patients (age 31 to 84 years) who showed progressive dementia or impaired consciousness served as disease controls. RESULTS: The percentage of DWI abnormalities was 92.3%, of PSWCs 50.0%, of 14-3-3 protein detection 84.0%, and of NSE increase 73.3%. Two of the 32 control subjects were falsely positive on DWI. The sensitivity of DWI was 92.3% (95% CI 74.8 to 99.5%) and specificity 93.8% (95% CI 79.2 to 99.2%). In 17 patients who did not show PSWCs on the first EEG, abnormal DWI findings were still clearly detected. Four patients who were negative for 14-3-3 protein also showed DWI abnormalities. DWI abnormalities were detected as early as at 3 weeks of symptom duration in four patients in whom PSWCs were not yet evident. CONCLUSIONS: DWI can detect characteristic lesions in the majority of patients with CJD regardless of the presence of PSWCs. DWI was the most sensitive test for the early clinical diagnosis of CJD; consideration should be given to its inclusion in the clinical diagnostic criteria of CJD.
The authors describe the clinical features of Creutzfeldt-Jakob disease (CJD) with the causative point mutation at codon 180. The symptoms never started with visual or cerebellar involvement. The patients showed slower progression of the disease compared with sporadic CJD. They never showed periodic sharp and wave complexes in EEG. MRI demonstrated remarkable high-intensity areas with swelling in the cerebral cortex except for the medial occipital and cerebellar cortices. These characteristic MRI findings are an important clue for an accurate premortem diagnosis.
We, for the first time, analyzed the binding motifs of immunoglobulin G (IgG) in the cerebrospinal fluid (CSF) of human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients with a phage library displaying 12-mer random peptides. As a result, the sequences highly homologous to HTLV-I gp46 192-199, 237-243 and 255-261 were the common linear epitopes of high affinity- IgG exclusively detected in both CSF and sera of the patients. These IgG responses were confirmed with corresponding HTLV-I peptides and serum antibody titers significantly correlated with disease severity or duration. Gp46 237-243 has not been detected in previous enzyme-linked immunosorbent assay (ELISA) studies using bound longer peptides, suggesting the usefulness of the phage display method.
Two Japanese sporadic Creutzfeld-Jakob disease (sCJD) patients with valine homozygosity at codon 129 of the prion protein gene and protease-resistant prion protein (PrP(Sc)) type 2 (VV2) are described. In contrast with Western countries, this type of sCJD is very rare in Japan. In 123 sCJD cases, only two were recognised as VV2 by the Japanese CJD surveillance committee. The clinical symptoms and pathological findings of the patients were similar to those of European and US patients. The noteworthy finding of diffusion weighted MRI (DWI) was that an abnormal high intensity covered a wide range of the thalamus including the dorsomedial nucleus, the pulvinar, and the ventral anterior, lateral, and posterolateral nuclei. This thalamic pattern has not been recognised in sCJD with methionine homozygosity and PrP(Sc) type 1 (MM1) or methionine/valine heterozygosity and PrP(Sc) type 1 (MV1) which comprises the vast majority of sCJD. This finding may be characteristic to VV2 and may distinguish it from MM1, MV1, and variant CJD. DWI can provide a very important clue for the antemortem diagnosis of VV2 subjects.
OBJECTIVES: To investigate the role of CSF hypovolemia in spontaneous intracranial hypotension (SIH) syndrome because so-called SIH syndrome sometimes lacks intracranial hypotension. METHODS: Ten women (aged from 28 to 49 years) with characteristic orthostatic headache without a previous history of dural tear were investigated. In addition to gadolinium (Gd)-enhanced brain MRI, spinal MRI with and without Gd enhancement was performed. RESULTS: Gd-enhanced brain MRI demonstrated diffuse pachymeningeal enhancement in all patients. Sagittal T2-weighted spinal MRI revealed a variable amount of CSF in the extradural space in all patients. Sagittal T2-weighted MRI or axial Gd-enhanced T1-weighted MRI showed dilated epidural veins located in the high cervical portion in each patient. The intensity of dilatation of the epidural veins correlated significantly with the amount of CSF in the epidural space. This suggested that the Monro-Kellie doctrine was applicable in this circumstance. CONCLUSIONS: Since some patients with SIH syndrome have normal CSF pressure and since a downward displacement of the brain due to a reduction of the buoyant action of CSF may induce symptoms, CSF hypovolemia, not intracranial hypotension, may be the cause. Based on the Monro-Kellie doctrine, detecting leaked CSF and venous engorgement (epidural vein dilatation and pachymeningeal enhancement) is an important clue to diagnose so-called SIH syndrome. Dilatation of epidural veins suggests CSF hypovolemia in appropriate conditions.
The authors describe a patient with sporadic distal myopathy associated with reduced caveolin-3 in muscle fibers in which the muscle atrophy was restricted to the small muscles of the hands and feet. Gene analysis disclosed a heterozygous 80 G-->A substitution in the caveolin-3 gene that was identical to that of reported cases of elevated serum creatine kinase. This patient further demonstrated possible clinical heterogeneity of myopathies with mutations in the caveolin-3 gene.
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We measured the central motor conduction time (CMCT), central sensory conduction time (CSCT), F wave and mean F wave/M wave amplitude ratio in patients with HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) and controls. CMCTs in upper (U) and lower (L) limbs were significantly prolonged in HAM/TSP. L-CSCT was significantly prolonged in HAM/TSP, but U-CSCT in HAM/TSP and controls were not significantly different. CMCT and CSCT were significantly correlated in HAM/TSP. U-CMCT, but not L-CMCT, correlated with the clinical severity of HAM/TSP. Although F wave conduction velocity and its occurrence were normal in HAM/TSP, U- and L-mean F wave/M wave amplitude ratio tended to be higher in HAM/TSP, and the L-mean F wave/M wave amplitude ratio was significantly correlated with the L- and thoracic CMCT. These findings demonstrate that the prolongation of CMCT sensitively reflects the extension of the lesions and the disinhibition to the anterior horn cells in HAM/TSP.
BACKGROUND: As outpatients with long-term chronic illness often show a high incidence of medication noncompliance, we investigated the influence of digoxin noncompliance on hospitalization, left ventricular ejection fraction, and mortality in outpatients in long-term therapy having congestive heart failure with tachycardia at a rate over 100 beats/min before starting digoxin therapy, but abnormal sinus rhythm. METHODS: Before starting this study, the digoxin compliance/noncompliance of patients was determined by measuring the serum digoxin concentration (SDC). SDC was determined once a month, followed for six consecutive months, and patients were defined as noncompliant if their SDC was zero (0.0 ng/ml) on at least three consecutive occasions. According to SDC data, 218 patients were assigned to the compliant group and 213 patients were assigned to the noncompliant group. All 431 patients received diuretics, angiotensin converting-enzyme inhibitors, or nitrates as well as conventional therapy with digoxin throughout the trial. The duration of follow-up was 72 months. FINDINGS: After 72 months of follow-up, the digoxin noncompliant patients showed significant increases in the number and duration of hospitalizations compared with the compliant patients. The digoxin noncompliant patients had a marked decrease in the left ventricular ejection fraction from 49.1% to 41.8%. The cumulative rate of mortality from any cause in noncompliant patients was twofold higher (15.0%) than in compliant patients (7.8%; risk ratio when noncompliant was compared with compliant: 1.95; 95% confidence interval 1.11, 3.45; P = 0.029) at the 72-month follow-up. The higher mortality in digoxin noncompliant patients was exclusively attributed to worsening heart failure rather than other cardiac and noncardiac causes (risk ratio 2.13; 95% confidence interval 1.12, 4.07; P = 0.033). In addition, multiple regression analyses demonstrated that patient noncompliance as well as lower left ventricular ejection fraction at baseline were significantly involved in increased mortality. CONCLUSION: These results indicate that digoxin noncompliance, at least in part, increases the rate of both hospitalization and mortality due to worsening heart failure in outpatients who have congestive heart failure with tachycardia in long-term therapy.
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To compare the diabetogenic activity of 20 kDa human growth hormone (20K-hGH) with that of 22K-hGH, we evaluated insulin sensitivity with a euglycaemic clamp in rats. The glucose infusion rate (GIR) in euglycaemic clamp studies was measured as an indicator of insulin sensitivity. [(14)C]glucose and 2-[(3)H] deoxy- D -glucose injection were used to calculate the rate of glucose utilization (R(d)), the hepatic glucose output (HGO), and the glucose metabolic index (R(g)'). Both 20K- and 22K-hGH were infused at equivalent rates (1.0 (mg/kg)/day). A 24 h infusion of 20K-hGH had no significant effects on the GIR, R(d), HGO and R(g)(')except for in gastrocnemius muscle. In contrast, 22K-hGH significantly lowered the GIR compared with the control (P< 0.001) and 20K-hGH groups (P< 0.01). The infusion of 22K-hGH also reduced R(d)compared with the controls and the 20K-hGH rats by 46.6% (P< 0.001) and 39.6% (P< 0.05) respectively, while no differences were observed in the HGO. Moreover, 22K-hGH inhibited glucose uptake, which was estimated from the insulin-stimulated R(g)' in some tissues. These results suggest that 22K-hGH inhibits the uptake and use of glucose in various tissues, which then leads to insulin resistance. In conclusion, the diabetogenicity of 20K-hGH is much weaker than that of 22K-hGH, and the reduced insulin-antagonizing action of 20K-hGH could have important clinical benefits.
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