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Biomedical subjects

I Goto

Publications and source records attributed to I Goto.

At least 37 records · Page 2Linked to original sources
PubMed1995

Characterization of cerebral white matter lesions of HTLV-I-associated myelopathy/tropical spastic paraparesis in comparison with multiple sclerosis and collagen-vasculitis: a semiquantitative MRI study.

The brain lesions were studied by magnetic resonance imaging (MRI) in 29 HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), 43 multiple sclerosis (MS) (11 with a primary progressive course: PPMS and 32 with a relapsing-remitting course: RRMS), 23 collagen-vasculitis and 54 HTLV-I-seronegative patients with other non-inflammatory neurological disorders (OND), according to the size of the lesions and their location in the brain (deep and subcortical white matter, periventricular white matter, infratentorial region and gray matter). Semiquantitative MRI analyses revealed the followings. (1) The frequency of either small or large lesions located in the periventricular as well as deep and subcortical white matter was significantly higher in HAM/TSP than in OND patients (p < 0.006, chi 2 test). In addition, the number of small lesions in the deep and subcortical, and periventricular white matter was significantly greater in HAM/TSP than in OND patients (p < 0.0003, Mann-Whitney U-test). (2) The HAM/TSP patients significantly exceeded the collagen-vasculitis patients in the frequency and the number of small lesions located in the periventricular region (p < 0.0001, chi 2 test, and p < 0.05, Mann-Whitney U-test, respectively), although no difference was found in case of those in the deep and subcortical white matter. (3) The HAM/TSP group had a lower frequency of small deep and subcortical white matter, small infratentorial and large periventricular lesions than the entire MS group (p < 0.05, chi 2 test). The PPMS group greatly exceeded the HAM/TSP group in the number of MRI lesions in all brain regions (p < 0.05, Mann-Whitney U-test), whereas RRMS and HAM/TSP patients showed a similar number of lesions (p > 0.1, Mann-Whitney U-test). Both the difference between HAM/TSP and collagen-vasculitis and the similarities between HAM/TSP and RRMS in the MRI features suggest that although all commonly have a vasculitic process as a necessary component, some other factor, probably with demyelinating effects, is operative HAM/TSP.

Adult↗
PubMed1995

Hepatitis C virus associated cryoglobulinemic neuropathy successfully treated with plasma exchange.

A 28-year-old Japanese woman who suffered from mononeuritis multiplex was admitted to our hospital. Serological study revealed cryoglobulinemia (type III), hypocomplementemia, high titers of rheumatoid factor (RF), and positive antihepatitis C virus (HCV) antibody. Nerve conduction velocities were slower in sensory nerves than in motor nerves. Biopsied sural nerve showed a marked decrease of myelinated fibers but no evidence of angitis. She received plasma exchange and cryoglobulinpheresis over a period of 2 months with approximately 2.0 L (40 ml/kg) of plasma replaced in each procedure. Both plasma exchange and cryoglobulinpheresis alleviated clinical symptoms, and nerve conduction velocities were improved in several nerves. The serum cryoglobulin level was markedly reduced after the treatment together with the recovery of the C4 level. Thus, complements appeared to be consumed in large quantities in the presence of cryoglobulinemia in this patient. Efficacy of cryoglobulinpheresis indicates the possibility that cryoglobulins produced in association with HCV infection played a role in damaging the nerve directly through the activation of the complement system.

Adult↗
PubMed1995

[Changes in the concentrations of nutrient components of human milk during lactation].

The total protein, lipid, lactose and calcium concentrations in breast milk were measured monthly from 1 month to 8-12 months postpartum in 26 lactating women. In order to determine whether changes in the milk composition were due to changes in the duration of lactation or the decline in the milk yield, or both, a linear regression analysis of the change rate of the milk composition against that of the milk volume was performed for the period from 5 to 12 months in 12 women for whom milk yield per day was measured in addition to the milk composition. Protein concentration decreased by about 30% during the first 6 months. Thereafter it increased significantly when the decrease in the milk yield was rapid but declined significantly when the decrease in the milk yield was gradual. The lactose concentration did not change during the first 10 months but somewhat increased thereafter. The calcium concentration remained steady during the 5 months but decreased significantly thereafter. The rate of change for calcium was not affected by the extent of decline in milk yield. No significant changes were observed in lipid concentration and calculated energy content during the 12 months of lactation.

Adult↗
PubMed1995

[Segmental muscular atrophy of unilateral upper limb associated with cervical disc herniation in a juvenile male].

A 25-year-old man first noticed atrophy of right upper arm at the age of 15. This symptom progressed for the following 3 years and then became stable. As he noted difficulty in elevating his right arm above the shoulder level, at the age of 25 he was admitted to our hospital. On neurological examination, he had right scapula alata, moderate atrophy and weakness of right triceps muscle. Right triceps reflex was absent. Other neurological examinations were normal. Needle electromyography revealed neurogenic patterns in the muscles of the C5-T1 segments. Cervical MRI and CT myelography revealed mild cervical disc protrusion toward the right side at the C5/6 level and atrophy of the middle and lower cervical cord on the right side, but nothing suggestive of the fexion myelopathy. The clinical manifestations of the patient resembled those of Hirayama disease, except for the distribution of the involved muscles. Since the most severely involved level of the cervical cord (C7 segment) corresponded to the level of the protruded cervical disc, it was suggested that the cervical disc herniation played an important role in the development of the myelopathy in this patient.

Adult↗
PubMed1994

Detection of human T lymphotrophic virus type I (HTLV-I) proviral DNA and analysis of T cell receptor V beta CDR3 sequences in spinal cord lesions of HTLV-I-associated myelopathy/tropical spastic paraparesis.

Identification of the localization of human T lymphotrophic virus type I (HTLV-I) proviral DNA in the central nervous system (CNS) is crucial to the understanding of the pathogenesis of HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP) pathogenesis. We have developed a sensitive detection method, called two-step polymerase chain reaction (PCR) in situ hybridization, which enabled us to detect the HTLV-I proviral DNA in paraffin-embedded spinal cord tissue sections from HAM/TSP patients. HTLV-I proviral DNA was detected only in the nucleus of lymphocytes that had infiltrated into the spinal cord. However, no proviral DNA was amplified in any neuronal cells, including neurons and glial cells. This indicates that the demyelination of the spinal cord by HTLV-I as a result of viral infection of oligodendrocytes or neuronal cells is unlikely. The T cell receptor V beta gene sequence from lymphocytes in the spinal cord lesions taken from the same HAM/TSP autopsy cases revealed unique and restricted CDR3 motifs, CASSLXG(G) (one-letter amino acid. X is any amino acid), CASSPT(G), and CASSGRL which are similar to those described in T cells from brain lesions of multiple sclerosis (MS) and in a rat T cell clone derived from experimental allergic encephalomyelitis (EAE) lesions. The present results suggest that T cells containing restricted V beta CDR3 motifs, which are also found in MS and EAE, become activated upon HTLV-I infection and infiltrate into the spinal cord lesions of HAM/TSP patients.

Adult↗
PubMed1994

Altered GABAergic effects on kainic acid-induced seizures in the presence of hippocampal sclerosis in rats.

Although deficient inhibitory action of GABAergic neurons is frequently implicated in the pathogenesis of epileptic seizures, their exact contribution to the epileptogenicity is still controversial. In the present study, we investigated the effects of GABAergic action on kainic acid (KA)-induced hippocampal seizure in rats with or without hippocampal sclerosis (HS). HS was produced by pretreatment of KA (12 mg/kg i.p.) 3 weeks prior to induction of acute KA seizure (8 mg/kg i.p.). After development of epileptiform activity in the hippocampus, either muscimol (50 ng/microliters, 1.0 microliter) or vehicle (phosphate buffer solution, 1.0 microliter) was applied locally in the left dorsal hippocampus through a cannula and electrobehavioral observation was performed continuously for 6 h. The seizures were divided into four stages according to their severity. 7 days after the induction of acute seizure, the rats were sacrificed and subjected to histological examinations. In the rats without HS, muscimol reduced the seizure severity as well as neuronal damage, whereas muscimol facilitated the severity of both indicators in the presence of HS. Muscimol accelerated the propagation of epileptiform activity and the onset of more advanced seizure stages regardless of presence or absence of HS. Our study suggest that the GABAa function has dual effects on the final severity of KA-induced seizure depending on the presence or absence of HS and that it accelerates the rate of seizure development in either condition. The altered GABAa function in the presence of HS would probably modify seizure activity.

Animals↗
PubMed1994

Adrenoleukodystrophy gene encodes an 80 kDa membrane protein.

An antibody against the synthetic C-terminal peptides deduced from the cDNA of the gene responsible for X-linked adrenoleukodystrophy (ALD) was produced to characterize the product of the ALD gene. The antibody reacted with the 80 kDa band protein in control fibroblasts, while no bands were detected in the fibroblasts from a patient with ALD (#163), in which mRNA of the ALD gene was undetectable based on Northern blot analysis. The 293T cells transfected with the full-coding cDNA inserted in the expression vector produced a new 80 kDa protein, as detected by Western blot. In an immunocytological study, the staining was in a punctate pattern, in the normal fibroblasts. However, there was no punctate staining in the #163 cells. These data thus indicate that the ALD gene encodes an 80 kDa membrane protein.

Adrenoleukodystrophy↗
PubMed1994

TNF-beta produced by human T lymphotropic virus type I-infected cells influences the proliferation of human endothelial cells and fibroblasts.

Human T lymphotropic virus type I (HTLV-I) is linked to adult T cell leukemia as well as to HTLV-I-associated myelopathy/tropical spastic paraparesis. In this report, we studied the effects of HTLV-I-infected cell supernatants on HUVEC, fibroblasts, and glioma cells. The HTLV-I-infected cell supernatants (HUT102 and MT-2) strongly inhibited the proliferation of HUVEC, although they enhanced the proliferation of the fibroblasts. Regarding the glioma cells, only the MT-2 supernatant showed weak inhibitory effects on the proliferation. However, the HTLV-I-uninfected cell supernatants showed no effects on these target cells. The biologic activities of both HUT102 and MT-2 supernatants were found to be dose dependent and were reduced by heat treatment at 100 degrees C for 5 min, but not at 56 degrees C for 30 min. These activities were not dependent on the concentrations of HTLV-I viral particles and were only minimally affected by the presence of anti-HTLV-I Abs. A bioassay of various cytokines revealed that the activity of TNF was much higher in the HUT102 and MT-2 supernatants than in the HTLV-I-uninfected cell supernatants (MOLT-4, Jurkat, and K-562). rTNF-alpha and rTNF-beta also showed strong inhibitory effects on HUVEC as well as on the enhancement of the fibroblast growth. With the use of Sephadex G-100 column chromatography, we obtained the highest activities from the 60- through 70-kDa fractions of the HUT102 supernatant and some activities from the 20- through 30-kDa fractions. The biologic activities of both the whole HUT102 supernatant and its active fractions were completely blocked by anti-TNF-beta mAb, although they were not blocked by anti-TNF-alpha mAb. In a Western blot assay, the 25- and 27-kDa bands of TNF-beta were shown clearly in the HUT102 supernatant, although no TNF-alpha bands appeared. These findings suggest that TNF-beta is present in either its oligomeric or monomeric form in the HTLV-I-infected cell supernatants and is also mainly responsible for the supernatants' effects on HUVECs and fibroblasts.

Cell Division↗
PubMed1994

Hemoglobin as a novel protein developmentally regulated in neurons.

We have attempted to identify some novel genes which were found to be more highly expressed in the embryonic brain than in the adult brain. Consequently, one of these clones was identified as alpha-globin cDNA. Actually, alpha-globin mRNA was detected in the neurons. In addition, beta-globin mRNA was detected in the neurons as well. Both globin mRNAs were developmentally regulated in the same pattern. Subsequently, further examinations with antiserum to hemoglobin revealed the presence of hemoglobin in the neurons. Hemoglobin has, up to now, been known to be an important O2 transporter protein in erythrocytes. Moreover, hemoglobin is now considered to be also a very dangerous protein generating the toxic hydroxyl radical (.OH). We herein show the presence of hemoglobin and its regulation in the central nervous system, which may indicate the presence of a useful function regulating O2 homeostasis and a potential oxidative toxicity for neuronal cells.

Animals↗
PubMed1994

Inhibition of the proliferation of cultured immortalized Schwann cells by forskolin with a decreased basal level of diacylglycerol.

The repetitive passages of a Schwann cell culture results in the appearance of immortalized cells. In order to investigate the direct effects of cyclic AMP (cAMP) on Schwann cell proliferation, we used the immortalized Schwann cells because the responses of a short-term Schwann cell culture to agents increasing the intracellular cAMP are more complicated and it does not seem that all of them are due to the direct effects of cAMP. By adding up to 200 microM of forskolin, an adenylate cyclase activator, to the culture medium, Schwann cell proliferation was inhibited and the intracellular 1,2-diacylglycerol (DG) level was decreased in a dose-dependent manner to 44 and 53% of the control values, respectively. The protein phosphorylation activity in the cytosol from the cell treated with 100 microM forskolin, assayed with myelin basic protein as the acceptor, decreased to 78% and this inhibition was then reversed by the addition of 1-oleoyl-2-acetyl-sn-glycerol (OAG), a membrane-permeable DG, to the assay mixture. The cell proliferation inhibited by forskolin was also restored by the addition of OAG. These data suggest that cAMP inhibits both the activity of protein kinase C (PKC) and consequently cell proliferation through suppression of intracellular DG level, an activator of PKC. Since the inositol 1,4,5-triphosphate level and the hydrolysis of phosphatidylcholine to DG and phosphorylcholine were not affected, forskolin therefore appears to suppress the de novo synthesis of DG.

Animals↗
PubMed1994

Allolymphocytotoxic antibodies in sera from HTLV-I-associated myelopathy/tropical spastic paraparesis patients--putative anti-HLA antibodies.

Thirty-one HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients and 34 asymptomatic carriers were studied in order to investigate the presence of anti-lymphocyte antibodies in their sera. 32% of the patients produced allolymphocytotoxic antibodies reactive to peripheral blood lymphocytes (mainly T cells) as well as to B cells, which belonged to the IgM class, reacted under warm and cold conditions, and showed specificity to multiple HLA antigens, especially HLA A2, A26, A33, B7, B27, B35, B48, B61 and Cw3. Moreover, their reactivities could be absorbed by pooled platelets. Therefore, it may be suggested that either anti-HLA class I antibodies or antibodies cross-reactive to HLA were present. On Western blot analysis, the HAM/TSP cytotoxic sera reacted to the 110 kDa molecules of lymphocyte lysates. In the case of carriers, weak cytotoxic antibodies were detectable in 14% of the sera. No multispecificity to HLA class I antigens was observed and there was no reactivity to the 110 kDa band. The production of allolymphocytotoxic antibodies in HAM/TSP patients may therefore be explained by the presence of allogeneic-like stimuli in this disease. HTLV-I infected cells, expressing altered HLA antigens could possibly account for this stimulation and also contribute to the alteration of immune functions in HAM/TSP, and thus play an important role in its pathogenesis.

Adult↗
PubMed1994

A riboflavin-responsive lipid storage myopathy due to multiple acyl-CoA dehydrogenase deficiency: an adult case.

A 62-year-old man was admitted to our hospital because of easy fatigability of the lower limbs during walking. The biopsied muscle specimen showed excessive lipid accumulation. The carnitine concentration in the muscle was at the lower level of the normal range. Organic acid urinalysis was consistent with the diagnosis of multiple acyl-CoA dehydrogenase deficiency or glutaric acidemia type II. In cultured lymphoblastoid cells from this patient there was impaired beta-oxidation, but the activities of acyl-CoA dehydrogenases were normal. Riboflavin therapy resulted in a dramatic improvement in both clinical and biochemical aspects. In this patient, the defect in coenzyme binding to electron transfer flavoprotein (ETF) or ETF-dehydrogenase was suspected. In the adult case of lipid storage myopathy, multiple acyl-CoA dehydrogenase deficiency should be suspected as one of its pathogenesis and riboflavin therapy should be considered.

Acyl-CoA Dehydrogenases↗
PubMed1994

Hypernatremic myopathy.

We describe a 21-year-old man presenting with proximal muscle weakness associated with hypernatremia. His manifestations other than muscle weakness included dry skin, loss of axillary and pubic hair, decreased libido and loss of thirst sensation. His serum sodium level was elevated to 169-171 mEq./l but all other electrolytes were normal. In addition, serum CK was elevated and an EMG study showed myogenic changes. Endocrinological studies revealed hypothalamic hypopituitarism, while MRI revealed a suprasellar mass. A partial correction of hypernatremia led to an immediate recovery of the muscle weakness as well as a normalization of both the serum CK level and EMG findings, suggesting a direct association between the muscle weakness and hypernatremia. The phosphocreatine/inorganic phosphorus (PCr/Pi) ratios in the resting calf muscle, obtained using 31P magnetic resonance spectroscopy (MRS), were very low during the state of muscle weakness, while they returned to nearly normal values after clinical improvement, suggesting that the muscle weakness in hypernatremic state was caused by a depletion of the intramuscular energy stores, probably due to an overworking Na-K pump to correct the intracellular electrolyte imbalance.

Adult↗
PubMed1994

Striatal 18F-dopa uptake and brain glucose metabolism by PET in patients with syndrome of progressive ataxia.

Striatal 18F-Dopa uptake and brain glucose metabolism were studied by PET with 6-L-[18F]flurodopa and [18F]fluorodeoxyglucose in 11 patients with syndrome of progressive ataxia. Five of the 11 patients were diagnosed as having cerebellar cortical degeneration (CCD), including 3 with late cerebellar cortical atrophy and 2 with Holmes type hereditary ataxia while 6 demonstrated olivopontocerebellar atrophy (OPCA). The caudate and putaminal 18F-Dopa uptake ratios to the occipital cortex in CCD showed no significant difference from those in the controls. On the other hand, those with OPCA decreased as compared to the controls. In addition, the cerebellar glucose metabolism in CCD decreased as compared to the controls, while that in the brainstem showed no significant decrease from the controls. The glucose metabolic rates both in the cerebellar hemisphere and in the brainstem in the OPCA patients decreased compared to the controls. The cerebral cortical, striatal and thalamic glucose metabolisms were normal in both the CCD and OPCA in groups. The appearance of a decreased glucose metabolism in the cerebellum is considered to be relevant in the genesis of cerebellar ataxia, even though their underlying diseases were different from each other. The differences in the glucose metabolism of the brainstem and in the nigrostriatal presynaptic dopaminergic function between CCD and OPCA as assessed by PET may be caused by differences in the pathophysiological mechanism between CCD and OPCA, and those differences appear to be useful when making a differential diagnosis of CCD and OPCA.

Adult↗
PubMed1994

The DNA diagnosis for bulbospinal muscular atrophy.

We showed the analysis of the androgen receptor gene in 6 patients with bulbospinal muscular atrophy (BSMA). Four of them had typical manifestations of Kennedy's disease, while the other 2 patients did not show androgen insensitive signs such as gynecomastia or testicular atrophy. Enlarged CAG repeats were found in 4 patients with typical Kennedy's disease and 1 patient without androgen insensitive signs. This fact suggests that the DNA diagnosis by analysis of the androgen receptor gene is very useful to distinguish Kennedy's disease from other forms of BSMA.

DNA↗
PubMed1994

Glucosylceramide and glucosylsphingosine metabolism in cultured fibroblasts deficient in acid beta-glucosidase activity.

The metabolism of glucosylceramide (GlcCer) and glucosylsphingosine (GlcSph) was studied using cultured fibroblasts deficient in acid beta-glucosidase activity. In fibroblasts from patients with Gaucher's disease, in vitro beta-glucosidase activities were 2.7-11.7% and 4.8-13.6% of control values when 4-methylumbelliferyl beta-D-glucoside and GlcSph were used as substrates, respectively. In spite of the enzyme deficiency, GlcCer and GlcSph, the natural substrates of the deficient enzyme, did not accumulate in the cells. When normal fibroblasts were incubated with conduritol B epoxide (CBE), a specific inhibitor of acid beta-glucosidase, the in vitro enzyme activities decreased dose-dependently (2.2-2.4% of control values at 50 microM CBE), and GlcCer and GlcSph accumulated in the cells at concentrations of CBE higher than 50 microM. To investigate the intracellular metabolism of GlcCer and GlcSph, either radioactive GlcCer or GlcSph was loaded onto cultured fibroblasts. In fibroblasts treated with a high dose of CBE (1 mM), the degradation of GlcCer and GlcSph was retarded (5-21% on day 7; normal range, 81-99%), while in fibroblasts from patients with Gaucher's disease, both the pattern and rate of the degradation of the lipids (83-97% on day 7) were almost the same as those seen in the control cells. These results indicate that in Gaucher's disease fibroblasts the intracellular metabolism of GlcCer and GlcSph is normal in spite of the deficiency in beta-glucosidase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Cells, Cultured↗