Biomedical subjects

I Goto

Publications and source records attributed to I Goto.

At least 19 recordsLinked to original sources

PubMed1999

[The clinical usefulness of high-dose intravenous immunoglobulin therapy for chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy].

To explore the optimum dose of intravenous immunoglobulin (i.v.Ig) for treating patients with chronic inflammatory demyelinating polyrneuropathy and multifocal motor neuropathy, we compared the usefulness of i.v.Ig among 3 treatment doses. Fifty-nine patients were randomly divided into three treatment dosage groups: 20 patients for Group I using 50 mg/kg/day x 5 days, 19 patients Group II using 200 mg/kg/day x 5 days, and 20 patients Group III using 400 mg/kg/day x 5 days. We assessed clinically and electrophysiologically the effectiveness of the treatment at 5 weeks after the initial infusion. For patients in Group I and II who had not improved (or worsened) with the first treatment, we gave a one-step larger dose in the second treatment (i.e. 200 mg/kg/day x 5 days for those who had been given 50 mg/kg/day x 5 days, 400 mg/kg/day x 5 days for those who had been given 200 mg/kg/day x 5 days) after more than 9 weeks. We found that 15% of the patients in Group I, 21% in Group II and 60% in Group III improved dose-dependently with the first intravenous immunoglobulin treatment. Seven (47%) of 16 patients in Group I and 4 (40%) of 11 patients in Group II improved after the second treatment with larger doses. Adverse reactions including chill sensation, fever, skin eruption and increase in blood GOT and GPT levels were transient and mild. One patient in Group III developed left hemiparesis showing the small infarction in the right thalamus during the course of the treatment, but the symptom was mild. In conclusion, the high-dose intravenous immunoglobulin therapy (400 mg/kg/day x 5 days) is useful for treating patients with CIDP and MMN, although care must be taken of the risk of causing cerebral infarctions.

Adolescent↗

PubMed1997

Positron emission tomography (PET) in Machado-Joseph disease.

Positron emission tomography studies on the regional cerebral glucose metabolism (rCMRglc) and 18F-fluorodopa (18F-Dopa) uptake were performed in 3 patients with Machado-Joseph disease (MJD), a dominantly inherited degenerative disease in the cerebellum, brainstem and basal ganglia. The rCMRglc in MJD was found to be significantly decreased in the cerebellum, brainstem, striatum and whole cerebral cortex in comparison to that in normal subjects. These results of rCMRglc were different from those for dominantly inherited olivopontocerebellar atrophy (dOPCA) or cerebellar cortical degeneration (CCD), however they were similar to those for sporadic olivopontocerebellar atrophy (sOPCA) and multiple system atrophy (MSA). The 18F-Dopa uptake in MJD was found to be significantly decreased in the putamen and relatively spared in the caudate, which was different from that of MSA. In addition, these results indicate that MJD showed a dysfunction, not only in the regions with apparent pathological involvement such as cerebellum, brainstem and nigro-striatal dopaminergic system, but also in the cerebral cortex and the striatum where no pathology could be observed using conventional morphological techniques.

Adult↗

PubMed1997

Nine-year follow-up study of bromocriptine monotherapy for Parkinson's disease.

A 9-year nationwide study of bromocriptine monotherapy and combination therapy with bromocriptine and levodopa in Parkinson's disease is reported. Eleven patients were on bromocriptine monotherapy, 35 patients were on combined treatment of bromocriptine and levodopa for a certain time during a 9-year period. Maintenance doses of bromocriptine at the end of the 9th year in the two groups were 11.1 mg/day in the monotherapy and 12.7 mg/day in the combination therapy group with levodopa. Changes in Hoehn and Yahr's grading between the time of trial start and the end of 108 months' treatment revealed that 5 of 11 cases in the monotherapy group remained in the same stages, the other 2 cases improved in condition from stage II to I, and another 4 deteriorated compared with pretreatment grade. On the other hand, 20 of 35 cases in the combination-therapy group reached more advanced stages, 3 patients moving to stage V. Four of them, however, improved, and 11 did not change at the end of 9 years of treatment. Although it is difficult to prove the neuroprotective effect of a dopamine receptor agonist, our long-term nation-wide collaborative studies will help us to answer the question of how bromocriptine works in pharmacokinetic aspects.

Aged↗

PubMed1996

Prognostic significance of germ line polymorphisms of the CYP1A1 and glutathione S-transferase genes in patients with non-small cell lung cancer.

CYP1A1 is responsible for the metabolic activation of benzo(a)pyrene in cigarette smoke, and high susceptibility to smoking-related lung cancer has been associated with the MspI polymorphism of the CYP1A1 gene. Individuals with a susceptible CYP1A1 genotype have been found to be at remarkably high risk when the genotype is combined with a deficient Mu-class glutathione S-transferase (GSTM1) genotype. In this study, we investigated the relationship between germ line polymorphisms of these genes and clinical characteristics or survival rates in 232 patients with non-small cell lung cancer (NSCLC). Statistical analysis revealed a significant association (P < 0.05) of the MspI polymorphism of the CYP1A1 gene with histological type, performance status (general conditions of patients), and the extent of the primary tumor (T-factor). On the other hand, the GSTM1 polymorphism was significantly associated with performance status, the extent of regional lymph node metastasis (N-factor), and the extent of distant metastasis (M-factor). NSCLC patients with at least one susceptible allele of the MspI polymorphism of the CYP1A1 gene [heterozygous genotype B or a rare homozygous genotype C; n = 131; median survival time (MST) = 24.2 months] were associated with a shortened survival compared with those with nonsusceptible homozygous alleles (genotype A; n = 101; MST = 65.2 months; P = 0.005 by log-rank test). Smokers with susceptible genotypes (n = 104; MST = 18.2 months) were markedly associated with a shortened survival compared with those with genotype A (n = 76; MST = 69.2 months; P = 0.024); such an association was not found among nonsmokers by genotypes. Genotype-dependent survival was also observed in patients at an advanced stage of disease (P = 0.010), but not in those at an early stage of disease (P = 0.382). Patients with the susceptible CYP1A1 genotype had remarkably shortened survivals when the genotype was combined with a deficient genotype GSTM1(-) (P = 0.017; degree of freedom = 3). Multivariate analysis by the Cox proportional hazards model also revealed that the CYP1A1 polymorphism was an independent prognostic factor in patients at a nonresectable advanced stage of NSCLC (P = 0.005; hazard ratio = 1.98; 95% confidence interval, 1.24-3.17).

Adult↗

PubMed1996

Increased preproenkephalin mRNA and preprotachykinin mRNA in the striatum of Rolling mouse Nagoya.

Although Rolling mouse Nagoya (RMN) has been considered to demonstrate cerebellar dysfunction, our previous metabolic and electrophysiological studies also revealed a dysfunction of the basal ganglia, with the presumable primary site of dysfunction being the striatum. In the present study, we investigated the neurochemical functions of the striatum. In RMN, both preproenkephalin mRNA and preprotachykinin mRNA increased significantly in the striatum, with unaltered GAD mRNA, [(3)H]spiperone binding, [(3)H]QNB binding and preprosomatostatin mRNA, thus indicating the dysfunction of striatal projection neurons. These findings support the hypothesis that the site of primary dysfunction in the basal ganglia is in the striatum of RMN.

Animals↗

PubMed1996

Antibody-dependent cell-mediated cytotoxicity (ADCC) in HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP)

Defects in immune surveillance mechanisms may allow increased replication of human T-lymphotropic virus type I (HTLV-I) in peripheral blood mononuclear cells in HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP). To explore this possibility, antibody-dependent cell-mediated cytotoxicity (ADCC) against HTLV-I infected cells in HAM/TSP and in asymptomatic HTLV-I-seropositive carriers (SPC), was studied. ADCC activity was significantly depressed in HAM/TSP compared to SPC subjects (p < 0.025) and was due to specific reduction in ADCC effector activity. On the other hand, there was no difference in antibody component of anti-HTLV-I ADCC (ADCC-Ab) activities between HAM/TSP and SPC, although patients with more severe forms of disease tended to have higher anti-HTLV-I ADCC-Ab activity. In HAM/TSP, depressed ADCC activity against HTLV-I due to reduced ADCC-effector activity may allow increased replication of HTLV-I which may implicate the development of inflammatory neuropathologic lesions of HAM/TSP.

Adult↗

PubMed1996

Enhancement of sensitivity of human lung adenocarcinoma cells to growth-inhibitory activity of interferon alpha by differentiation-inducing agents.

A low concentration of differentiation inducers such as dimethylsulphoxide (DMSO), sodium butyrate, hexamethylene bisacetamide and sodium phenylacetate greatly enhanced the antiproliferative effect in vitro and in vivo of interferon alpha (IFN-alpha) to several human lung adenocarcinoma cells. The agents induced morphological changes in the adenocarcinoma cells and the agents together with IFN-alpha-induced alkaline phosphatase activity, which is a typical marker of type II pneumocyte maturation. To understand the mechanism of the DMSO-enhanced interferon sensitivity, we examined the effect of DMSO on high-affinity IFN-alpha receptor and interferon-stimulated promoter-binding factors. The lung adenocarcinoma cells were not impaired in IFN-alpha receptor and interferon-stimulated gene transactivation factor 3 (ISGF-3). Our data suggest that the enhancement of interferon sensitivity in the lung adenocarcinoma cells acts downstream of the activation of ISGF-3.

Acetamides↗

PubMed1996

Eight-year follow-up study of bromocriptine monotherapy for Parkinson's disease.

An 8-year nationwide study of bromocriptine monotherapy and combination therapy with bromocriptine and levodopa in Parkinson's disease is reported. Fifteen patients were on bromocriptine monotherapy, and 44 patients on bromocriptine combined with levodopa for a certain time during an 8-year period. By judging from Hoehn and Yahr's grading, 4 of the 15 patients in the monotherapy group were in a better condition than before treatment, while 7 cases remained in the same grading, and only 4 showed deterioration. On the other hand, 26 of 44 patients on combination therapy showed more advanced grading at the end of 8 years compared to the stage at the onset of the trial. Maintenance doses of bromocriptine in the two groups were 12-13 mg per day, and levodopa doses were kept at a relatively low level (310-370 mg per day) during this study period. Whether dopamine receptor agonists have neuroprotective effect or not is extremely difficult to prove in human subjects, but this type of long-term follow-up study might give some clues as to these important questions.

Aged↗

PubMed1996

Interferon-alpha is effective in HTLV-I-associated myelopathy: a multicenter, randomized, double-blind, controlled trial.

A double-blind, multi-center study was performed on patients with HTLV-I-associated myelopathy (HAM) to evaluate the therapeutic effect of treatment with natural interferon-alpha (HLBI). Forty-eight HAM patients were enrolled and treated with either 0.3 MU (n = 15), 1.0 MU (n = 17), or 3.0 MU (n = 16) of HLBI for 28 days. Clinical evaluation included motor dysfunction, urinary disturbances, and changes of neurologic signs. The frequency of therapeutic response judged as excellent to good 4 weeks after starting therapy and 4 weeks after completion of therapy were 7.1% (1 of 14) and 8.3% (1 of 12) in the 0.3-MU group, 23.5% (4 of 17) and 26.7% (4 of 15) for the 1.0-MU group, and 66.7% (10 of 15) and 61.5% (8 of 13) for the 3.0-MU group. The therapeutic benefit in the 3.0-MU group was significantly higher than in the 0.3-MU group. There was no significant difference in the incidence of symptomatic side effects between groups. Abnormal laboratory data were obtained for some patients in the 1.0-MU and 3.0-MU groups; however, the treatment schedule could be continued in most patients. These results suggest that HAM patients may be safely treated with HLBI 3.0 MU every day for 4 weeks with favorable clinical effects.

Adult↗

PubMed1996

Hemolytic anemia in wild seaducks caused by marine oil pollution.

Clinico-pathological examinations were conducted on wild white-winged scoters (Melanitta fusca) contaminated with fuel oil (Bunker C oil) from a capsized cargo ship in February 1993 in Japan. The erythrocyte count, hemoglobin concentration and hematocrit value in the oiled seaducks all were decreased and numerous immature erythrocytes were observed in blood smears. In addition, hemosiderosis was observed in the liver, kidney, and lung of some birds. We propose that the sea-ducks suffered from hemolytic anemia induced by ingestion of oil, which occurs when the birds preen their oiled plumage.

Alanine Transaminase↗

PubMed1996

[Gastrointestinal metastasis from lung cancer].

Metastasis of lung cancer to the digestive tract (excluding the esophagus) was confirmed by surgery or autopsy in 30 of the 1635 lung-cancer patients admitted to this Center during the 17-year period since 1977. The diagnosis was made before death in 7 and after death in 23. Metastasis of large cell carcinoma was the most common (3.7%), followed by adenocarcinoma (2.4%), small cell carcinoma (1.7%), and squamous cell carcinoma (0.7%). Metastasis to the stomach occurred in 0.4%, to the small intestine in 1.1% and to the colon in 0.5%. The overall percentage of metastasis to the digestive tract was 1.8%. Among the 298 cases diagnosed at autopsy, metastasis to the digestive tract occurred in 9.7%; stomach, 2.6%; small intestine, 5.7%; and colon, 3.0%. Eleven of the patients in whom the diagnosis was made at autopsy had abdominal symptoms while they were alive. In 11 cases diagnosed at autopsy, occult blood was positive in 9, but 6 of those 9 patients were asymptomatic. The occult-blood test is considered to be helpful as a supplementary diagnostic method in detecting metastasis of lung cancer to the digestive tract. Among the cases diagnosed while the patients were alive, metastasis was observed in the small intestine in 6 and in the colon in 1. The major manifestations were melena, ileus, intussusception, and perforation; 4 patients required emergency surgery. The prognosis was poor: the mean survival period from the onset of symptoms was 49 days. The direct cause of death was metastasis to the digestive tract in 5 cases. The possibility of metastasis to the digestive tract is high when progressive abdominal symptoms are observed and the stool is persistently positive on occult-blood tests.

Adenocarcinoma↗

PubMed1996

[A family of autosomal dominant facio-limb-girdle muscular dystrophy].

A family of autosomal dominant facio-limb-girdle muscular dystrophy was reported. The proband was a 28-year-old male. His father and sister suffered from a similar disease. All patients developed weakness of lower limbs and atrophy of thigh at second to fourth decades. All showed mild facial and neck flexor weakness as well as proximal dominant weakness and atrophy of four limbs. Limb muscle involvement was more severe in lower limbs than in upper limbs in all cases. Interestingly, all showed limitation of ankle dorsiflexion (tight heel cord), although distal muscles of lower limbs were not involved or only mildly involved clinically. On laboratory examination, serum CK increased slightly. Needle EMG revealed low amplitude, polyphasic MUP in limb muscles in all cases. Biopsied muscles taken from the proband showed non-specific myogenic changes. Rimmed vacuoles were not observed. Our cases were different from Bethlem myopathy, because the age of onset was late and joint contractures were mild in our cases, as compared with Bethlem myopathy. Clinical manifestations of our family showed a strong resemblance to the family reported by Girchlist et al, but similar cases were not reported in Japan.

Adult↗

PubMed1995

Apolipoprotein E mRNA in the brains of patients with Alzheimer's disease.

To clarify the role of apolipoprotein E (apoE) in the pathophysiology of Alzheimer's disease (AD), we used an RT-PCR method to investigate apoE and glial fibrillary acidic protein (GFAP) mRNA expression in the brain. ApoE mRNA was significantly more abundant in AD (0.379 +/- 0.191, mean +/- SD) than in control (0.125 +/- 0.073, p < 0.05) brain tissue, but in AD it was decreased in relation to the apoE-epsilon 4 gene dosage. The GFAP mRNA content also was greater in AD (5.96 +/- 2.94) than in control (3.80 +/- 2.78) tissue, and in AD showed an increase relative to the apoE-epsilon 4 gene dosage. AD patients who had long survival times showed high expression of apoE and low expression of GFAP. These results suggest that apoE suppresses the progression of AD, including gliosis, in the brain.

Adult↗

PubMed1995

Molecular analysis of X-linked adrenoleukodystrophy patients.

A molecular analysis of 4 Japanese adrenoleukodystrophy (ALD) patients was carried out, according to the recently published report on ALD gene cDNA. In a Southern blot analysis, we were not able to detect a large deletion in all patients. In a Northern blot analysis, no mRNA was detected in one patient, while the others had normal mRNA in both size and amount. Three patients had missense mutations including; 534Pro-->Leu (1987C-->T), 660Arg-->Trp (2364C-->T), and 512Gly-->Ser (1920G-->A), respectively. These mutations existed in the C-terminal region conserved in the ATP-binding cassette superfamily of transporters. In a Western blot analysis using polyclonal antibodies against the C-terminal peptide as well as the whole peptide of ALD protein, no 80 kDa protein was found in any of the 4 patients, which was observed in the control cells. The ALD protein in 3 patients with a missense mutation might be degraded immediately after translation because of the unstable higher structure or by the disruption of the hitherto unknown targetting signal to the peroxisome. The molecular analysis of the ALD gene as done in this study is thus considered to be the first step to further elucidate the pathogenic mechanism of ALD.

Adrenoleukodystrophy↗

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↗