[Metabolic nervous system diseases].
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Adolescent↗
Biomedical subjects
I Goto
Publications and source records attributed to I Goto.
Production of recombinant human transthyretin with biological activities toward the understanding of the molecular basis of familial amyloidotic polyneuropathy (FAP).
Transthyretin (TTR) is a plasma protein interacting with thyroxine T4 and retinol binding protein (RBP). Several variants of TTR with single amino acid substitutions have been identified as the major components of the amyloid fibrils of familial amyloidotic polyneuropathy (FAP), a fetal, autosomal dominant genetic disease. The elucidation of the molecular nature of the variants distinct from that of the wild-type TTR is crucial for understanding the amyloidogenesis in FAP, but our understanding is very poor mainly because of the unavailability of pure variant TTRs. In the present study, we used an Escherichia coli OmpA secretion vector (Ghrayeb et al., 1984) and achieved an effective production of the variant TTRs related to FAP including Met-30, Ile-33, Ala-60, Tyr-77, Met-111, and Ile-122 types. The variant TTRs produced in this system were efficiently secreted to the culture media. The chemical analysis showed that the secreted TTR (Met-30 type) has the same N-terminus as the native one. IEF analyses also indicated that the secreted product is properly processed as assessed by its pI. Furthermore, the secreted TTR was shown to have biological activities, namely, the thyroxin binding activity and the ability to associate with retinol binding protein, indicating that the secreted TTR polypeptide is properly folded. The present work also demonstrated that the processing/secretion of the recombinant TTR molecules in E. coli was strongly affected by single amino acid substitutions.
Amino Acid Sequence↗
A sensitive assay of lysogangliosides using high-performance liquid chromatography.
Lysogangliosides, LGM1, LGM2 and LGM3, each carrying a single sphingoid base (i.e., C18:1, C18:0, C20:1, C20:0), were prepared and a sensitive assay method of these lipids using HPLC was developed. The method involves fluorescence derivatization of the free amino group of the molecule with o-phthalaldehyde, separation of the molecular species of each lysoganglioside using reversed-phase HPLC and assay on the basis of a known amount of one of the lysogangliosides, as the internal standard. Using this method, lysoganglioside can be accurately assayed in the range of 5-1000 pmol. For assay of the lipid in the tissue, crude isolation procedures including extraction of lipids, Folch's partition and DEAE-Sepharose and AG 1-X2 column chromatographies were required before the fluorescence derivatization. In the normal human and the bovine cerebral cortex, 0.4-2.0 pmol/mg protein of LGM1 containing C18:1 and C20:1 sphingosine residues were detected. In the frontal cortex from a patient with Sandhoff disease, an abnormal accumulation (55-78 pmol/mg protein) of LGM2 was noted. Among various molecular species, LGM2 containing C18:1 was the most abundant.
Animals↗
Increased HTLV-I proviral DNA in HTLV-I-associated myelopathy: a quantitative polymerase chain reaction study.
Using the polymerase chain reaction, we quantitated the amount of human T-lymphotropic virus type I (HTLV-I) proviral DNA in peripheral blood mononuclear cells from 18 patients with HTLV-I--associated myelopathy/tropical spastic paraparesis; 17 HTLV-I carriers without HTLV-I--associated myelopathy/tropical spastic paraparesis, with or without other autoimmune or inflammatory diseases; and 19 seronegative control subjects. The HTLV-I proviral DNA was 10- to 100-fold higher in the patients and in the HTLV-I carriers without HAM/TSP who had autoimmune or inflammatory diseases than in the carriers without autoimmune or inflammatory diseases. The patients who had had onset of myelopathy at a younger age (15 to 39 years) had an extremely high level of HTLV-I proviral DNA in the early phase, as compared with findings in those with a late onset of myelopathy (at 44 to 61 years). The large increase in HTLV-I proviral DNA in peripheral blood mononuclear cells is presumably closely related to the development of autoimmune or inflammatory processes in HTLV-I carriers, including HTLV-I--associated myelopathy/tropical spastic paraparesis.
Adult↗
Early loss of astrocytes in herpes simplex virus-induced central nervous system demyelination.
Immunohistochemistry was used to study herpes simplex virus type 1-induced central nervous system demyelination in the trigeminal root entry zone of mice inoculated with herpes simplex virus type 1 by the corneal route. There was no change in peripheral nervous system myelin as shown by immunostaining for P0 glycoprotein. Double immunoperoxidase staining for herpes simplex virus type 1 antigens and glial fibrillary acidic protein showed that most of the infected cells were astrocytes. Glial fibrillary acidic protein immunostaining was completely lost in the inferior medial portion of the trigeminal root entry zone at 6 days after herpes simplex virus type 1 inoculation, a time when central nervous system myelin was preserved as indicated by immunostaining for myelin basic protein. The pattern of glial fibrillary acidic protein staining did not change and herpes simplex virus type 1 antigens were no longer detected after day 8. There was a progressive loss of myelin basic protein staining within the area unstained by glial fibrillary acidic protein antisera on days 8 to 14. This pattern of astrocyte loss before central nervous system demyelination is strikingly different from the reactive astrocytosis seen in other demyelinating lesions, such as acute experimental allergic encephalomyelitis, progressive multifocal leukoencephalopathy, or acute multiple sclerosis. Herpes simplex virus type 1 infection in mice provides an unusual model of acute central nervous system demyelination preceded by a loss of astrocytes.
Animals↗
Chorea-acanthocytosis: abnormal composition of covalently bound fatty acids of erythrocyte membrane proteins.
Phospholipid class, peak profile of each phospholipid class, loosely bound fatty acids, covalently (tightly) bound fatty acids of the erythrocyte membranes, and plasma fatty acids were investigated using high-performance liquid chromatography in six patients with chorea-acanthocytosis and 14 age- and sex-matched normal control subjects. Additionally, six patients with Huntington's disease were included as disease control subjects in the study of covalently bound fatty acids. Study of covalently (tightly) bound fatty acids in erythrocyte membrane proteins after alkaline hydrolysis, hitherto undescribed in chorea-acanthocytosis, revealed that palmitic acid (C16:0) was significantly increased and stearic acid (C18:0) was decreased in the patients with chorea-acanthocytosis. Analyses for total covalently bound fatty acids disclosed that palmitic and docosahexaenoic (C22:6) acids were increased and stearic acid was decreased in chorea-acanthocytosis. Phospholipid class (phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, and phosphatidylserine) and peak profile of each phospholipid class from the erythrocyte membranes did not differ between the patients with chorea-acanthocytosis and the control subjects. Of the loosely bound fatty acids, linoleic acid (C18:2) was significantly decreased in those with chorea-acanthocytosis, which seemed to be nonspecific.
Acanthocytes↗
Adrenoleukodystrophy: a correlation between saturated very long-chain fatty acids in mononuclear cells and phenotype.
Saturated very long-chain fatty acids in erythrocyte membranes, blood plasma, and mononuclear cells were studied in 4 patients with childhood-adolescent adrenoleukodystrophy and 4 patients with adult adrenoleukodystrophy and 19 normal control subjects by using high-performance liquid chromatography. Ratios of C26:0 to C22:0 in mononuclear cells, erythrocyte membranes, and blood plasma in patients with childhood-adolescent and adult adrenoleukodystrophy were significantly higher than in normal control subjects. Furthermore, ratios of C26:0 to C22:0 in mononuclear cells were significantly higher in patients with childhood-adolescent adrenoleukodystrophy than in patients with adult adrenoleukodystrophy, whereas there was no significant difference in the ratios in erythrocyte membranes and blood plasma between the two groups of patients with adrenoleukodystrophy. These results suggest that there is a correlation between phenotype and ratio of C26:0 to C22:0 within mononuclear cells in patients with adrenoleukodystrophy.
Adolescent↗
Magnetic resonance imaging of the muscles in patients with polymyositis and dermatomyositis.
Magnetic resonance imaging (MRI) of the muscles was performed in patients with polymyositis and dermatomyositis. Lesions with high intensity on T2-weighted image, but normal intensity on T1-weighted image, were observed in 7 of 8 patients in the active stage of the disease. Following clinical improvement with corticosteroid therapy in 4 patients, the high intensity lesions reverted to normal. The high intensity lesions seen on T2-weighted image in the active stage may represent edema and inflammation of the muscle. MRI of the muscle may serve as a diagnostic tool and be useful for follow-up of the patients with polymyositis or dermatomyositis.
Adult↗
Hyperprolactinemia in multiple sclerosis.
In order to clarify endocrine abnormalities due to hypothalamic involvement in multiple sclerosis (MS), serum prolactin levels were measured in 27 patients with MS and 22 healthy subjects. The presence of hypothalamic lesions was also studied by magnetic resonance imaging (MRI). Serum prolactin levels were found to be significantly higher in MS patients than in healthy controls in both sexes. Although only one patient had galactorrhea, one-third of the MS patients had mild to moderate hyperprolactinemia, which was a 4-13-fold increase over the mean value of healthy subjects. The results of thyrotropin-releasing hormone, sulpiride, L-DOPA and bromocriptine loading tests suggested a hypothalamic dysfunction, rather than pituitary prolactinoma in MS patients. Four of eight patients with hyperprolactinema had diencephalic hypothalamic lesion(s) contiguous with the third ventricle on the brain MRI, while none of the normoprolactinemic patients had any lesions in the diencephalon. All relapsing-remitting patients with hyperprolactinemia showed a rise in prolactin levels in the acute stage of the relapse and a decrease during the recovering stage and the following remission phase. Our findings suggest that latent hyperprolactinemia due to hypothalamic dysfunction occurs frequently in MS patients in relapse. The increase of serum prolactin is considered to be a sensitive indicator for hypothalamic lesions in MS.
Adult↗
Cellular immune surveillance against HTLV-I infected T lymphocytes in HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP).
To investigate the cellular immune surveillance against HTLV-I infected T lymphocytes in HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP), we studied the cytotoxic T lymphocytes (CTL) activity against an HTLV-I infected human T cell line (MT-2) and the natural killer (NK) cell activity in 15 HAM patients, 6 HTLV-I carriers, and 15 controls. The activity of CTL against MT-2 cells was found to be significantly elevated in HAM compared with that in the controls. This cytotoxicity in HAM was higher than in HTLV-I carriers, although the difference was not statistically significant. There was an HLA class I restriction in this CTL activity against MT-2 cells in HAM. On the other hand, NK cell activity was significantly lower in HAM than in controls. Cold target inhibition studies suggested that NK cells could not lyse MT-2 cells effectively. There was a positive correlation between the CTL activity against MT-2 cells and the serum antibody titers to HTLV-I in HAM.
Adult↗
Analysis of prognostic factors in thymectomized patients with myasthenia gravis: correlation between thymic lymphoid cell subsets and postoperative clinical course.
We retrospectively examined the postoperative clinical course of 50 consecutive patients with myasthenia gravis who underwent a transsternal extended thymectomy. Twenty-six patients (52%) showed a steady improving postoperative course without any additional immunotherapy (group A). The remaining 24 patients (48%) had an intractable postoperative course, and most of them needed additional immunotherapy (group B). A significant increases in CD3+ cells, HLA-DR+ cells and B-cells and significant decreases in CD1+ cells and CD8+ cells were observed in the thymuses from patients in group B, compared with the findings in group A. In the peripheral blood, the ratio of CD4+ cells to CD8+ cells was significantly increased in group B. Patients who were either under 40 years of age, females, or without thymoma had good clinical courses after the thymectomy alone.
Adult↗
Leukoencephalopathy in HTLV-I-associated myelopathy/tropical spastic paraparesis: MRI analysis and a two year follow-up study after corticosteroid therapy.
Magnetic resonance imaging (MRI) of the brain was studied in 35 patients with HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP), 19 HTLV-I seropositive carriers without HAM/TSP (non-HAM/TSP carriers), 18 patients with HTLV-I seronegative spastic spinal paraparesis (SSP), and 82 HTLV-I seronegative controls with other neurological disorders. The incidence of white matter lesions was significantly higher in HAM/TSP (66%) than in the controls (23%) and SSP (11%). HAM/TSP exceeded non-HAM/TSP carriers significantly in the incidence of multiple white matter lesions (37% vs 10%). HAM/TSP affected the deep and subcortical cerebral white matter multifocally, sparing the periventricular regions. None of the lesions were enhanced by gadolinium-DTPA. HAM/TSP patients with the white matter lesions had both a longer duration of disease and a greater disability than did those without lesions. The white matter lesions gradually increased in number, as the disability status became worse, in spite of the high dose corticosteroid treatment. All these observations suggest that the MRI abnormalities of the HAM/TSP brain may reflect the chronic perivascular inflammation with progressive gliosis (chronic disseminated encephalomyelitis). We propose that brain MRI can be successfully utilized as a reliable and non-invasive measure for following the disease progression in HAM/TSP.
Age Factors↗
Natural killer (NK) cells in HTLV-I-associated myelopathy/tropical spastic paraparesis-decrease in NK cell subset populations and activity in HTLV-I seropositive individuals.
We examined natural killer (NK) cell activity and NK cell subset populations in 18 patients with HTLV-I associated myelopathy (HAM)/tropical spastic paraparesis (TSP), ten HTLV-I seropositive asymptomatic carriers and 20 seronegative healthy controls. The NK cell activity was significantly decreased in HAM/TSP, compared with that in controls. The percentages of NK cell subsets, such as CD16+, CD11b+, CD56+, CD16+ CD56-, CD16-CD56+, CD16+CD8-, or CD16+CD3+ cells were significantly decreased in HAM/TSP patients. Of particular interest is that the percentage of CD16+CD3+ cells, which have a wide spectrum of cytotoxic properties commonly seen in NK, lymphokine activated killer (LAK) and antibody-dependent cellular-cytotoxic (ADCC) effector cells, was significantly decreased in HAM/TSP as compared to asymptomatic carriers as well as controls. The percentage of CD16+CD3+ cells correlated inversely with the value of spontaneous proliferation of peripheral blood lymphocytes (SPP), which is a characteristic change observed in HAM/TSP.
Adult↗
A possible association between HLA and HTLV-I-associated myelopathy (HAM) in Japanese.
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Asian People↗
Clustering of three cases of Creutzfeldt-Jakob disease near Fukuoka City, Japan.
During a 4-month period we encountered three patients with Creutzfeldt-Jakob disease (CJD). All lived in a limited area near Fukuoka City in Japan. Such a significantly close spatial and temporal clustering of cases suggests exposure to a common CJD infectious agent. Except for dental-related treatments, there were no evident causative agents common to these three patients.
Aged↗
Striatal blood flow, glucose metabolism and 18F-dopa uptake: difference in Parkinson's disease and atypical parkinsonism.
Striatal blood flow, glucose metabolism and 18F-Dopa uptake were studied with positron emission tomography (PET) in eight non-demented patients with idiopathic Parkinson's disease and eight with atypical Parkinsonism. Patients with atypical Parkinsonism had no specific cause for the Parkinsonian symptoms and were clinically different from Parkinson's disease with lack of resting tremor and a poor response to dopaminergic drugs. Decreased 18F-Dopa uptake in the putamen was observed in patients with Parkinson's disease and atypical Parkinsonism compared with normal controls. 18F-Dopa uptake in the head of the caudate was also significantly reduced in both conditions but relatively less in Parkinson's disease. Decreased blood flow and glucose metabolism in the striatum associated with a global cerebral decrease were also observed in patients with atypical Parkinsonism compared with controls, while they were preserved in patients with Parkinson's disease, indicating affected neurons not only in the striatum but also in the cerebrum in patients with atypical Parkinsonism compared with patients with Parkinson's disease. The differences in the caudate 18F-Dopa uptake, and blood flow and glucose metabolism in the cerebrum including the striatum between Parkinson's disease and atypical Parkinsonism assessed by PET may be due to the differences in the pathophysiological mechanism between Parkinson's disease and atypical Parkinsonism.
Adolescent↗
A nationwide collaborative study on the long-term effects of bromocriptine in patients with Parkinson's disease. The fourth interim report.
The interim results of the nationwide collaborative study on the long-term effects of bromocriptine in patients with Parkinson's disease are reported. Four years ago, two prospective clinical studies were started to evaluate the long-term effects of bromocriptine in Parkinson's disease. The first was to investigate the long-term effects of bromocriptine monotherapy and the second to see the long-term effects of a combination therapy of bromocriptine with levodopa. Patients who had never been treated with levodopa were placed on bromocriptine monotherapy, and those who had been treated with levodopa for not more than 5 years were allocated randomly to either the combination or the levodopa group. Two hundred and eighty-six patients were enrolled in the former study and 416 in the latter. Among the 286 patients, 164 continued for further observation at the end of the fourth year, and 74 of them were still being treated with bromocriptine monotherapy. However, in 78, levodopa had to be added. Among the 416 patients in the second study, 216 were allocated to the combination group and 200 to the levodopa control group. At the end of the fourth year, 130 in the former and 140 in the latter group remained for further observation. In all three groups, a gradual loss of efficacy was noted. The rate of efficacy loss appeared largest in the monotherapy group and smallest in the combination group. Effects on tremor and rigidity are still maintained, but effects on akinesia and gait were lost by the end of the fourth year in all groups. Wearing-off and dyskinesias seem to be better managed by the combination therapy. The incidence of wearing-off was very small in the monotherapy group. No serious side effects were encountered except for 1 patient who died of pulmonary fibrosis in the combination group.
Bromocriptine↗
Expression of Alzheimer amyloid beta-protein precursor gene in neuronal cells.
Five forms of Alzheimer amyloid beta-protein precursors (APP or BPP) have been found. Among them, APP695 is predominantly found in neuronal cells and may be involved in some neuronal functions. In the present work, we investigated the relationship between the APP expression and the formation of neurites, a typical neuronal morphology, by measuring the amounts of three major APP mRNAs in PC12 cells, using the polymerase chain reaction. In PC12 cells, nerve growth factor which induced a neurite formation, enhanced the expression of APP695. The ratio of APP695 to APP770 increased 2.6-fold after 6 days of treatment. Cyclic AMP also induced a similar morphological change, but did not affect the APP expression pattern. Thus, the neuronal expression of the APP gene is not directly related with neurite formation. We have also identified cis-elements for the neuronal expression of APP gene.
Alzheimer Disease↗