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Biomedical subjects

I Goto

Publications and source records attributed to I Goto.

At least 55 records · Page 3Linked to original sources
PubMed1994

The synthetic pathway for glucosylsphingosine in cultured fibroblasts.

The synthesis of glucosylsphingosine (GlcSph), a glucosylceramide (GlcCer) analogue devoid of fatty acids, in cultured fibroblasts was studied by using conduritol beta epoxide (CBE), an inhibitor of beta-glucosidase, and 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP), an inhibitor of glucosylceramide (GlcCer) synthase (glucosyltransferase). When CBE was added to the culture medium, the intracellular beta-glucosidase activity decreased, and both GlcCer and GlcSph accumulated in the cells. After the addition of PDMP, the concentration of GlcCer decreased, while the content of GlcSph increased. When CBE and PDMP were added together, the intracellular accumulation of GlcSph to decreased to less than when CBE alone was added. Based on these results, the synthetic pathway for GlcSph was thus considered to not only be through the glucosylation of sphingosine, but also through the deacylation of GlcCer. When GlcCer (d18:1, C12:0) was added to the culture medium, the intracellular accumulation of GlcSph (d18:1) was evident, and it was also more pronounced in the presence of CBE. In addition, when GlcCer (d18:0, C12:0) was used, apparent accumulation of GlcSph (d18:0) was also observed. In order to determine whether or not the deacylase of GlcCer is identical to acid ceramidase, a deacylase of ceramide, the same experiments were carried out using fibroblasts from two patients with Farber disease, in which acid ceramidase is genetically deficient. The accumulation of GlcSph in the Farber disease fibroblasts after the loading of GlcCer for 7 days was found to be one-fifth of the control level.(ABSTRACT TRUNCATED AT 250 WORDS)

Acylation↗
PubMed1994

Recurrent opticomyelitis associated with anti-DNA antibody.

Two patients had frequent attacks of acute myelitis and optic neuritis. One patient lacked any other organ involvement whereas the other developed systemic manifestations of systemic lupus erythematosus 14 years after the onset. Both patients developed antinuclear and antidouble strand DNA antibodies after the onset of neurological involvement. These patients, whose neurological manifestations were indistinguishable from multiple sclerosis, were thus considered to have systemic lupus erythematosus related collagen disease.

Adult↗
PubMed1994

Seven-year follow-up study of bromocriptine therapy for Parkinson's disease.

A 7-year nationwide study of bromocriptine monotherapy and combination therapy with bromocriptine and levodopa in Parkinson's disease is reported. Of 22 patients who had been on bromocriptine monotherapy for 7 years (group B), 16 remained improved or remained in the same stages of Hoehn and Yahr, and no wearing-off phenomenon or dyskinesia was observed. In another 56 patients who were started on bromocriptine alone, but in whom combination therapy with levodopa was instituted at some time in the 7 years (group BL), disease progressed faster than in group B. A wearing-off phenomenon and dyskinesia occurred in 34% and 5.4% of the patients, respectively. These manifestations appeared only after initiation of levodopa. The favorable course of group B suggests possible neuroprotective effects of bromocriptine or may be due to the inevitable selection of patients who had a favorable course originally.

Adult↗
PubMed1994

Japanese family with Creutzfeldt-Jakob disease with codon 200 point mutation of the prion protein gene.

We report the first Japanese case of familial Creutzfeldt-Jakob disease (CJD) with the heterozygous point mutation at codon 200 of the prion protein gene. This suggests that the mutation is not race-specific. The clinical and pathologic features of this case are not different from those of sporadic CJD without point mutations. Some healthy members of the family also carry the same mutation in the autosomal dominant inheritance expression.

Adolescent↗
PubMed1994

Vitamin B12 metabolism and massive-dose methyl vitamin B12 therapy in Japanese patients with multiple sclerosis.

Serum vitamin B12 levels and unsaturated vitamin B12 binding capacities were measured in 24 patients with multiple sclerosis (MS), 73 patients with other neurological disorders and 21 healthy subjects. There was no decrease in the vitamin B12 levels, however, a significant decrease in the unsaturated vitamin B12 binding capacities was observed in patients with MS when compared with other groups. A massive dose of methyl vitamin B12 (60 mg every day for 6 months) was administered to 6 patients with chronic progressive MS, a disease which usually had a morbid prognosis and widespread demyelination in the central nervous system. Although the motor disability did not improve clinically, the abnormalities in both the visual and brainstem auditory evoked potentials improved more frequently during the therapy than in the pre-treatment period. We therefore consider that a massive dose methyl vitamin B12 therapy may be useful as an adjunct to immunosuppressive treatment for chronic progressive MS.

Adult↗
PubMed1994

[Causative factors and neurological diseases].

Considering the pathogenesis of neurological diseases, it is important to determine causative factors directly affecting the nervous system. We discussed here some neurological diseases induced by exogenous agents (thallium, organic phosphorus, organic solvents, acrylamide) and by "endogenous" agents (Krabbe disease, Alzheimer disease, familial amyloidotic polyneuropathy). In diseases by exogenous toxic agents, it is not very difficult to find the toxic factors. However, because a single agent can induce a variety of clinical symptoms, we should consider the dose of the agents, the toxic mechanisms and the susceptibility of tissues or organs. In endogenous diseases, causative agents are either toxic factors or the substances inducing mechanical injury. Endogenous toxic agents are usually produced by affected cells themselves. In the case of the substances inducing mechanical injury, the pathogenesis is more complex. The structure of the abnormal agents and tissue susceptibility should be considered.

Acrylamide↗
PubMed1994

[Acute relapsing sensory-dominant polyneuropathy associated with anti-GQ1b antibody and autoimmune hepatitis].

A 43-year-old male with 2 episodes of sensory impairments in four extremities and liver dysfunction, developed an acute exacerbation of both sensory impairments and liver dysfunction after administration of interferon-alpha. On admission, neurological examination revealed a mild distal weakness of four extremities, moderate impairment of superficial sensation in hands and severe impairment of deep sensation and areflexia in all extremities. Routine laboratory tests were normal except for a mild liver dysfunction. His serum was positive for antinuclear antibody, but negative for anti-DNA antibody and LE-test. Since he was seropositive for hepatitis B (HB) c antibody but seronegative for HBs antigen and antibody, HBe antigen and antibody, he was considered to be a seroconverted carrier of HB virus. Liver biopsy revealed chronic active hepatitis with marked lymphocytic infiltration. CSF examinations were within normal limits. Sensory conduction studies of median and sural nerves showed no response, but motor conduction studies of median and peroneal nerves were within normal limits. Light and electron microscopic examination of biopsied sural nerve disclosed a moderate decrease in large myelinated fibers, but not in either small myelinated or unmyelinated fibers. Thin-layer chromatography with immunostaining showed the presence of anti-GQ1b antibody in his serum. The anti-GQ1b antibody did not react with GT1a. Oral administration of prednisolone alleviated liver dysfunction, muscle weakness and superficial sensory impairment of four extremities, but not in deep sensation.

Acute Disease↗
PubMed1994

[Effects of maternal food intake on the total protein, fat, lactose and calcium concentrations in human milk].

The concentrations of total protein, fat, lactose and calcium (Ca) in human milk were measured in 68 lactating women who were 14-425 days postpartum. Relationships of those concentrations in human breast milk with maternal food intake frequency, and the amount of dairy milk intake were investigated. Quantification theory III statistical analysis was applied to analyze food intake patterns. The concentrations of total protein at 2-5 months postpartum, fat and Ca at 1-5 months postpartum were low in milk obtained from mothers with low frequency of consumption of meat, egg, dairy products and food prepared with oil, while having a high frequency of consumption of rice, vegetables, beans and seaweed. The concentration of Ca in milk from mothers who habitually had no dairy milk intake was significantly lower compared to that from mothers who had more than 300 ml intake of dairy milk per day. Lower frequency or no intake of animal food and dairy milk appeared to affect the quality of mother's milk.

Adult↗
PubMed1994

[Relationship between volume and concentrations of various components of breast milk in early and 2-6 months lactation].

The concentrations of total protein, fat, lactose, calcium and s-IgA in human colostrum and matured milk and 24-hour milk production for the same day were measured on 99 and 47 lactating women at 5 days and 2-6 months post-partum, respectively. Relationships between measured concentrations, calculated energy content, and milk volumes were investigated. 1. In colostrum, the concentrations of protein and s-IgA showed significant negative correlations with milk volumes, while those of fat and lactose, and energy content showed significant positive correlations with milk volumes. 2. In matured milk, the concentrations of protein and s-IgA showed significant negative correlations with milk volumes. However, the negative correlation between protein concentration and milk volumes was not statistically significant when subjects were limited to mothers breast-feeding only. In matured milk fat, lactose and calcium concentrations, and energy content were not significantly correlated with milk volume.

Adult↗
PubMed1994

Mechanism of hemolysis of canine erythrocytes induced by L-sorbose.

The cause of species difference in the susceptibility of erythrocytes to L-sorbose, and the difference in the hemolytic effect of sorbose on high potassium-containing (HK) and low potassium-containing (LK) canine erythrocytes were examined. L-Sorbose was phosphorylated in canine erythrocytes, but not in human erythrocytes. Furthermore, sorbose-1-phosphate, a metabolite of L-sorbose, strongly inhibited the hexokinase of LK canine erythrocytes, but not that of HK canine erythrocytes. These results strongly indicated that inhibition of hexokinase by sorbose-1-phosphate in LK erythrocytes induced severe glycolytic limitation in these cells, resulting in hemolysis, and that HK erythrocytes are resistant to sorbose-induced hemolysis because these cells have a high hexokinase activity.

Animals↗
PubMed1993

Neuron-specific splicing of the Alzheimer amyloid precursor protein gene in a mini-gene system.

Several forms of Alzheimer amyloid precursor protein (APP) mRNA are generated by alternative splicing. Among them, the APP695 mRNA skipping the exon 7 and 8 is expressed specifically in neurons, suggesting that this alternative splicing is regulated in a neuron-specific manner. As the first step for investigating the mechanism of the neuron-specific splicing, a mini-gene system was developed, in which mini-APP genes consisting of the exon 6, 7, 8, 9 and their flanking regions were introduced into neuronal and nonneuronal cultured cell lines to see their expression profiles. In the system the exon 7 and 8 of the mini-gene were significantly skipped in the neuronal cell, and the deletion study indicated that cis-acting elements for skipping the exons existed in the corresponding skipped-exon and its flanking regions. A small deletion upstream of the exon 8 suppressed the skipping of the exon 8 in the neuronal cell, suggesting that one of the regulatory sequence(s) for the exon skipping exists in a small region upstream of the skipped exon.

Alternative Splicing↗
PubMed1993

Involvement of protein kinase C in the proliferation of cultured Schwann cells.

We investigated the signal transduction system when the proliferation of cultured Schwann cells was activated by glial growth factor (GGF). When 10 micrograms/ml of GGF was added to the culture medium, Schwann cell division was activated by about 3-fold, while protein kinase C (PKC) activity was translocated from the cytosol to the particulate fraction, and diacylglycerol (DG) production was increased in the cells. PKC activity in the particulate fraction and intracellular DG content increased to 167% and 158%, respectively. However, intracellular cyclic AMP levels remained unchanged. The GGF-induced proliferation of Schwann cells was significantly inhibited by staurosporine, a PKC inhibitor, in a dose-dependent manner, while H-8, a specific inhibitor for cyclic nucleotide-dependent protein kinases, did not show an inhibitory effect even at a high concentration. These data suggest that the signal transduction system through PKC is involved in the proliferation of Schwann cells when treated with GGF.

Animals↗
PubMed1993

In vivo infection of human T-cell leukemia virus type I in non-T cells.

Using three different procedures, immunomagnetic isolation, FACS and panning, each of the T4 cell, T8 cell, monocyte, and B cell population was fractionated from peripheral blood mononuclear cells (PBMC) obtained from 10 human T cell leukemia virus type I (HTLV-I)-associated myelopathy (HAM)/tropical spastic paraparesis (TSP) cases, 3 adult T cell leukemia and lymphoma (ATLL) cases and 9 HTLV-I-infected healthy carriers. DNA from each fraction was then subjected to the quantitative polymerase chain reaction. Although T4 cells possessed the highest copy number of HTLV-I in general, we also detected a significant amount of HTLV-I provirus in T8 cells, monocytes, and B cells. To confirm virus infection of the non-T cell populations, especially the monocyte fraction, we performed further experiments and the following results were obtained: (1) HTLV-I tax RNA expression was confirmed simultaneously in the RNA of monocytes that were negative for T cell receptor beta chain (TCR beta) expression in vivo. (2) We cultured these monocytes for a short period of time and detected HTLV-I antigen expression in non-specific esterase-positive monocyte/macrophage cells. Our data indicate that HTLV-I has a broad host range in vivo and that monocytes or cells of monocyte lineage such as tissue macrophages might comprise a virus reservoir in vivo.

B-Lymphocytes↗
PubMed1993

Positron emission tomographic (PET) studies in dementia.

Positron emission tomographic (PET) studies of regional cerebral glucose metabolism were performed in patients with various types of dementia, patients with Parkinson's disease but without dementia, and healthy normal controls. Patients with Alzheimer-type dementia showed significant decreases in glucose metabolism in frontal, temporal, parietal, sensory-motor and striatal regions. Patients with Pick's disease revealed decreased glucose metabolism in frontal and temporal regions. Parkinsonian patients with dementia had significant reductions of glucose metabolism in frontal, temporal, parietal, occipital, sensory-motor and striatal regions. Patients with Huntington's disease revealed decreased glucose metabolism in frontal, parietal and striatal regions. Patients with Creutzfeldt-Jakob's disease showed marked decreases in glucose metabolism throughout all brain regions. On the other hand, patients with Parkinson's disease but without dementia exhibited no reductions of cerebral glucose metabolism. Cerebral glucose hypometabolism in these various types of dementia might reflect neuronal dysfunction and cell death.

Adult↗
PubMed1993

Chronic progressive spinocerebellar syndrome associated with antibodies to human T-lymphotropic virus type I: clinico-virological and magnetic resonance imaging studies.

The relationship between HTLV-I infection and the development of spinocerebellar degeneration (SCD) in adulthood was studied. The frequency of anti-HTLV-I antibodies among patients with SCD (8 of 43, 19%) was found to be higher than the seroprevalence rate in the northern part of Kyushu island (6%). All HTLV-I carriers with SCD showed chronic progressive cerebellar ataxia as a predominant feature and cerebellar atrophy was evident in 6 of 8 patients on magnetic resonance imaging (MRI) of the brain. However, SCD patients with anti-HTLV-I antibodies showed a significantly higher frequency of cerebral white matter lesions on brain MRI (6 of 8) and pyramidal tract signs in lower extremities (6 of 8) than did those without the antibodies (35%, P < 0.05 and 26%, P < 0.01, respectively). Moreover, the HTLV-I carriers with SCD exceeded 14 HTLV-I carriers having neither SCD nor HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP) (21%, P < 0.05), and 59 HTLV-I seronegative patients without brain disorders (19%, P < 0.001) in the frequency of white matter lesions. On the other hand, the HTLV-I carriers with SCD were distinct to the HAM/TSP patients in the predominance of cerebellar involvement. Therefore, the peculiar features of cerebellar, pyramidal and white matter involvement in the HTLV-I-seropositive SCD patients as well as the increased frequency of HTLV-I infection among SCD patients suggest that this syndrome may be a distinct subtype of HTLV-I-associated neurologic diseases.

Aged↗
PubMed1993

Primary progressive versus relapsing remitting multiple sclerosis in Japanese patients: a combined clinical, magnetic resonance imaging and multimodality evoked potential study.

Thirty-five Japanese patients with relapsing remitting multiple sclerosis (RRMS) and 11 Japanese patients with primary progressive MS (PPMS) were compared by a combined clinical, magnetic resonance imaging (MRI) and multimodality evoked potential (MEP) study. Patients with PPMS showed a more common occurrence of gait disturbance as the initial symptoms as well as a more common occurrence of cerebellar symptomatology than did those with RRMS, while spinal cord symptomatology was frequently observed in both conditions. On brain MRI, patients with PPMS had 3 times more lesions than did those with RRMS (P < 0.001, chi 2-test). The percentage of infratentorial lesions was also significantly higher in PPMS than in RRMS on MRI. Moreover, we found a significantly higher frequency of abnormal records in visual, brainstem auditory and somatosensory evoked potentials in PPMS than in RRMS. Interestingly, clinically unexpected abnormalities were significantly more common in PPMS than in RRMS throughout all modalities of MEPs. Thus, in Eastern MS, there exists a distinction between PPMS and RRMS in the MRI and MEP findings as well as in the clinical findings. Our result therefore suggest that there may be two distinct subtypes in MS.

Adult↗
PubMed1993

Cerebral glucose metabolism and striatal 18F-dopa uptake by PET in cases of chorea with or without dementia.

Cerebral glucose metabolism was studied by positron emission tomography with [18F]fluorodeoxyglucose in 12 patients with chorea due to different underlying diseases. The striatal 18F-dopa uptake was also studied with 6-L-[18F]fluorodopa in 6 of them. Five of them were diagnosed as Huntington's disease two were as 'sporadic progressive chorea and dementia' with characteristic symptoms and signs of Huntington's disease but no family histories, two were as choreoacanthocytosis, and two had hemichorea caused by suspected vascular lesions in the contralateral striatum revealed by MRI. Caudate and putaminal glucose metabolism decreased in chorea compared to the controls. Hemichorea showed decreased glucose metabolism only in the contralateral striatum. Moreover the glucose metabolism decreased in demented each 7 patients in the frontal, temporal and parietal cortices as well as in the striatum. The caudate and putaminal 18F-dopa uptake in patients with chorea showed no difference with that in the controls. The pathogenetic mechanism of chorea may involve decreased glucose metabolism and normal presynaptic dopaminergic activity in the striatum, and that of the demented state in chorea may also involve an additional decrease of the glucose metabolism in the frontal, temporal and parietal cortices.

Adult↗