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Biomedical subjects

Sadako Kuno

Publications and source records attributed to Sadako Kuno.

30 records · Page 2Linked to original sources
PubMed2003

Biopterin metabolism in patients with malignant syndrome.

We examined the autopsied brains of two parkinsonian patients who had malignant syndrome (MS). Neopterin and biopterin contents, and GTP cyclohydrolase I activity were measured in various region of the brain. We found relatively higher GTP cyclohydrolase I activities in the hypothalamus compared with other regions of the brain from patients with MS. This finding suggested a possible involvement of biopterin metabolism in pathophysiology of MS. This is the first report on biopterin metabolism in the brains of patients with MS.

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PubMed2003

A collaborative study on the malignant syndrome in Parkinson's disease and related disorders.

We report the results of a collaborative study on malignant syndrome (MS) that developed in patients being treated with levodopa and other anti-parkinsonian drugs. We analyzed clinical features, laboratory findings, precipitating events, and risk factors for poor outcome. The study was conducted in five centers in Japan. Patients who developed MS between January 1991 and December 1997 were included. The enrollment criteria used were the same as those for neuroleptic MS proposed by Levenson et al. (1985).A total of 99 episodes were encountered in 93 patients (72 with Parkinson's disease and 21 with secondary parkinsonism); one patient had four recurrences of MS and three patients had two recurrences. High fever was the most frequent clinical manifestation of MS followed by worsening of parkinsonism, and then altered levels of consciousness. Serum creatine kinase was abnormally elevated in all the patients studied. Life-threatening complications were rhabdomyolysis, disseminated intravascular coagulation, and acute renal failure. The most frequent precipitating event was discontinuation or dose reduction of anti-parkinsonian drugs, particularly levodopa. No drug was the exception in the precipitation of MS. Intercurrent infection was the next most common precipitating event. MS developed without drug withdrawal or infection in some patients. In five patients, severe "wearing off" phenomenon was the only event preceding the onset of MS. Hot weather and dehydration appeared to be the cause in three patients. Among the total of 99 episodes, patients recovered to the pre-MS state following 68 episodes (68.7%); in the remaining 31.3%, patients failed to recover to their previous state. Older age, higher Hoehn and Yahr stage during the symptomatic phase of MS, higher akinesia score, and the absence of wearing off phenomenon prior to developing MS were associated with poor outcome. The most frequently used treatments of MS were intravenous fluid, levodopa, dantrolene sodium, and intragastric bromocriptine. Early introduction of treatment is important. Any elevation of body temperature during the course of anti-parkinsonian drug treatment should be considered as MS until proved otherwise.

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PubMed2003

Prevention and treatment of malignant syndrome in Parkinson's disease: a consensus statement of the malignant syndrome research group.

We report a consensus statement of the collaborative research group on the prevention and treatment of malignant syndrome (MS) in Parkinson's disease. The syndrome is quite similar to neuroleptic MS. Although sudden withdrawal of levodopa was the most frequent cause, many other precipitating events were found such as intercurrent infections, dehydration, hot weather, discontinuation of other anti-parkinsonian drugs, and "wearing off" phenomenon. Awareness of this syndrome is most important for its early detection and the prompt commencement of treatment. MS should be suspected whenever the body temperature rises above 38 degrees C without an apparent cause. Treatment consists of ample intravenous fluid, cooling the body, anti-parkinsonian drugs (particularly levodopa and bromocriptine), dantrolene sodium, and antibiotics if infection is present. Rhabdomyolysis, disseminated intravascular coagulation, and acute renal failure constitute serious complications.

Antiparkinson Agents↗
PubMed2003

Malignant syndrome in Parkinson's disease: concept and review of the literature.

We reviewed literature on malignant syndrome occurring in patients with Parkinson's disease (PD) during the course of drug therapy. Clinical features were high fever, marked rigidity, consciousness disturbance, autonomic dysfunction, and elevation of serum creatine kinase. The clinical features were essentially similar to those of neuroleptic malignant syndrome. The immediate triggering event was, most often, discontinuation or reduction of anti-parkinsonian drugs, particularly of levodopa. But no anti-parkinsonian drug was the exception to the induction of malignant syndrome. Serious complications were severe pneumonia, disseminated intravascular coagulation, and acute renal failure. Early treatment with intravenous fluid infusion and external body cooling are essential for good recovery. Bromocriptine and dantrolene sodium were used frequently. It has been claimed that they are effective; however, randomized controlled studies are needed to explicitly prove the efficacy of these drugs in malignant syndrome associated with PD.

Antiparkinson Agents↗
PubMed2003

Dopaminergic mechanisms underlying bladder hyperactivity in rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal pathway.

1. This study was undertaken to elucidate dopaminergic mechanisms underlying bladder hyperactivity in a rat model of Parkinson's disease (PD) induced by a unilateral 6-OHDA injection into the substantia nigra pars compacta. 2. In 6-OHDA-lesioned rats, voided volume per micturition (0.41+/-0.04 ml, mean+/-s.e.m.) measured during 24 h in a metabolic cage was significantly smaller than in sham-operated rats (0.67+/-0.07 ml). 3. Cystrometrograms (CMG) in conscious animals revealed significantly smaller bladder capacity (BC) (0.46+/-0.03 ml) in 6-OHDA-lesioned rats than in sham rats (0.72+/-0.06 ml). 4. SKF38393 (D1/D5 receptor agonist, i.v.) significantly increased BC in 6-OHDA rats without apparent effects in sham rats. SKF38393 applied intracerebroventricularly (i.c.v.) under urethane anesthesia also increased BC in 6-OHDA-lesioned rats and by a smaller increment in sham rats. 5. In contrast, quinpirole (D2/D3/D4 receptor agonist, i.v.) significantly reduced BC in sham and 6-OHDA-lesioned rats. Intrathecal injection of quinpirole similarly reduced BC in sham and 6-OHDA-lesioned rats. 6. PD128907 (D(3)-receptor agonist) did not have significant effects on BC in 6-OHDA-lesioned rats. 7. These results indicate that a rat model of PD exhibited bladder hyperactivity as observed in patients with PD, and that stimulation of D1/D5 dopamine receptors at a supraspinal site can suppress bladder hyperactivity in PD, whereas stimulation of D2/D4, but not D3, dopamine receptors had the opposite effect to reduce bladder capacity. Thus, D1/D5 dopamine receptor agonists might be effective in treating neurogenic bladder hyperactivity in PD.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed2003

Frequency of anti-AChR epsilon subunit-specific antibodies in MG.

A definite diagnosis of myasthenia gravis (MG) relies heavily on acetylcholine receptor (AChR) antibody testing. The relatively high number of antibody-negative patients therefore, causes frequent uncertainty in confirming the diagnosis. We evaluated the sensitivity and specificity of a new, commercially available AChR antibody test that uses an approximately equal mixture of AChR from TE671-epsilon (adult type) and TE671-gamma (fetal type) cells. This assay was used to re-examine 365 seronegative MG sera in which AChR antibody had not been detected by the standard assay that uses fetal type AChR. The new assay detected anti-AChR antibodies in 17 (15.5%) of 110 patients with ocular type and in 33 (12.9%) of 255 patients with generalized type MG. Anti-AChR epsilon subunit-specific antibodies were present in 13.7% of the patients in whom no AChR antibody had been detected by the standard assay, showing an increase from 79 to 82% in overall diagnostic sensitivity.

Antibodies↗
PubMed2003

Relationship of bladder dysfunction to lesion site in multiple sclerosis.

PURPOSE: We investigated the relationship of voiding dysfunction type and the lesion site in patients with multiple sclerosis. MATERIALS AND METHODS: Voiding dysfunction was evaluated in 32 patients with multiple sclerosis using the International Prostate Symptom Score and urodynamic tests. Lesion sites were determined by combined neurological examination and magnetic resonance imaging findings. RESULTS: Compared with reports from Western countries the ratio of emptying-to-filling symptoms was high in Japan. Of urinary symptoms only filling correlated with disability status and disease duration. Urinary symptoms were not related to lesion sites. Urodynamic evaluation revealed detrusor hyperreflexia in 14 of 32 patients, hyporeflexia or areflexia in 12, detrusor hyperreflexia with impaired contractile function in 4, a low compliance bladder in 1 and normal function in 1. Of 14 patients with hyperreflexia 13 had overactive sphincter concurrently. Incompetent sphincter was identified in 2 patients who had detrusor hyperreflexia with impaired contractility and in 1 with a low compliance bladder. A significant correlation was noted for a pontine lesion and detrusor hyporeflexia, and for a cervical cord lesion and detrusor-sphincter dyssynergia. CONCLUSIONS: Detrusor hyporeflexia and detrusor-sphincter dyssynergia are indicative of a pontine and cervical spinal cord lesion, respectively. Thus, the lesion site in the central nervous system may be a major determinant of the type of bladder and urethral sphincter dysfunction. The high prevalence of emptying symptoms in Japanese patients may reflect the prevalence of detrusor hyporeflexia and detrusor-sphincter dyssynergia.

Adolescent↗
PubMed2003

Apomorphine attenuates 6-hydroxydopamine-induced apoptotic cell death in SH-SY5Y cells.

Enhanced oxidative stress is implicated in the pathogenesis of Parkinson's disease. The catecholaminergic neurotoxin 6-hydroxydopamine (6-OHDA) induces the production of reactive oxygen species (ROS), leading to neuronal cell death. On the other hand, apomorphine, a dopamine D1/D2 receptor agonist and known as a potent antioxidant, has been reported to have a neuroprotective effect. In the present study, we investigated the effect of apomorphine on 6-OHDA-induced apoptotic cell death using the human dopaminergic neuroblastoma cell line, SH-SY5Y. The co-treatment of cells with apomorphine significantly attenuated 6-OHDA-induced ROS generation, the phosphorylation of c-Jun N-terminal kinase (JNK), DNA fragmentation and subsequent apoptotic cell death. In addition, pretreatment with apomorphine for 24 h and the following concomitant treatment enhanced the protective effects against 6-OHDA-induced toxicity except for the attenuation of JNK phosphorylation. We also demonstrated that pretreatment alone with apomorphine for 24 h prior to the exposure confers resistance against 6-OHDA-induced cell toxicity. These findings suggested that apomorphine acts principally as a radical scavenger to suppress the level of ROS and ROS-stimulated apoptotic signaling pathway, whereas the other mechanisms might be involved in the protective effects.

Antiparkinson Agents↗
PubMed2002

The novel catecholaminergic and serotoninergic activity enhancer R-(-)-1-(benzofuran-2-yl)-2-propylaminopentane up-regulates neurotrophic factor synthesis in mouse astrocytes.

We investigated the effects of the novel catecholaminergic and serotoninergic activity enhancer R-(-)-1-(benzofuran-2-yl)-2-propylaminopentane ((-)-BPAP) on the synthesis and secretion of neurotrophins, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and glial cell line-derived neurotrophic factor (GDNF), in cultured mouse astrocytes. The protein and mRNA levels of the neurotrophic factors were measured using the enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction methods, respectively. The amounts of NGF, BDNF, and GDNF secreted from astrocytes into the culture medium increased by up to 120, two, and seven times higher than those of the control, respectively, by treatment with 0.35 mM (-)-BPAP for 24 h. The increases in NGF and GDNF induced by the treatment with (-)-BPAP was inhibited by concomitant treatment with actinomycin D for transcriptional blockade. Furthermore, the treatment with (-)-BPAP for 6 h increased the mRNA expression of NGF, BDNF, and GDNF. These results suggest that (-)-BPAP up-regulated neurotrophic factor synthesis in cultured astrocytes.

Animals↗
PubMed2002

Contribution of the interleukin-1beta gene polymorphism in multiple system atrophy.

We studied genetic polymorphisms in the promoter region at position -511 of the interleukin (IL) -1beta gene (IL-1B-511) and at position -889 of the IL-1alpha gene (IL-1A-889), in 111 Japanese patients with multiple system atrophy (MSA) and 160 controls. The distribution of IL-1B-511 was significantly different between MSA patients and controls, because of the under-representation of patients with homozygotes for allele 2 (IL-1B-511*2), a high producer of IL-1beta. The frequency of IL-1A-889*2, a high secretor of IL-1alpha, was also decreased in MSA patients. Our findings suggest that abnormal cytokine expression may be implicated in the pathogenesis of MSA.

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