Biomedical subjects

K Urakami

Publications and source records attributed to K Urakami.

At least 55 records · Page 3Linked to original sources

PubMed1996

Presenilin-1 polymorphism in patients with Alzheimer's disease, vascular dementia and alcohol-associated dementia in Japanese population.

We investigated the genetic association between intronic polymorphism in Presenilin-1 (PS-1) gene and patients with various types of dementia such as Alzheimer's disease (AD), vascular dementia (VD) and alcohol associated dementia (ALD), in Japanese population. Homozygosity for allele 1 of the PS-1 polymorphism was significantly increased in late-onset sporadic AD, but not in early-onset sporadic AD, familial AD, VD and ALD. When late-onset sporadic AD patients were divided on the basis of apolipoprotein E (APOE) genotype, homozygosity for the allele 1 of the PS-1 polymorphism was significantly increased in patients with late-onset sporadic AD without APOE epsilon 4 allele, but not in those with APOE epsilon 4 allele. Intronic mutation in PS-1 gene may be specific and one of the genetic risk factor for late-onset sporadic AD.

Age of Onset↗

PubMed1996

Prevalence of neurological disorders in a Japanese town.

The prevalence of all neurological disorders in a Japanese town was calculated, with a result of 91.1 per 1,000 population. The prevalence of cerebrovascular disease was 28.8; myelopathy and/or radiculopathy caused by deformity of the spine or disc herniation, 23.9; neuralgia, 11.5; dementia, 10.4; peripheral nerve disturbance, 5.5; epilepsy, 4.4; Parkinson's disease, 2.0; mental retardation, 2.9; brain/spinal tumor, 1.4; headache, 10.8, and vertigo/dizziness, 4.4. The prevalence of headache and vertigo/dizziness was also calculated from the results of the questionnaires sent to inhabitants: headache, 79.6, and vertigo/dizziness, 60.8. Neurological disorders are common in Japan and likely to continue to increase.

Adolescent↗

PubMed1996

Effects of biscoclaurine alkaloid cepharanthine on newborn rat skin epidermal and dermal cells.

Effects of biscoclaurine alkaloid cepharanthine on proliferation of skin cells were examined in vitro. The alkaloid was found to enhance attachment and cell layer formation of newborn rat skin epidermal cells in culture on type I collagen-coated Millipore filter, and to potentiate production of keratins in these cells. Spreading and growth of skin dermal fibroblasts were inhibited by cepharanthine in a dose-dependent manner, but the alkaloid-treated cells still retained the ability to synthesize type IV collagen. In culture of skin cells containing both epidermal and dermal cells, no growth of epidermal cells or over-growth of dermal fibroblasts was observed in medium without cepharanthine. In contrast, the presence of the alkaloid suppressed the growth of fibroblasts and promoted the formation of epidermal cell layers accompanied by production of keratins. Thus, in comparison with the cells untreated with the alkaloid, cepharanthine-treated skin epidermal and dermal cells in vitro expressed in vivo-like characters.

Alkaloids↗

PubMed1996

Effect of culture matrix on newborn rat skin basal cells; modification of cell response to extracellular calcium.

Basal cells from newborn rat skin epidermis were cultured on various culture matrixes, and the response of the cells to extracellular calcium was examined. When the cells were cultured on a type I collagen-coated Millipore filter to maintain clearance under the cultured cells as intact skin, the cells responded to a fluctuation in extracellular calcium and were detached from the collagen layer in a high calcium environment. In this case, protein synthesis of the cells increased calcium-dependently. In contrast, calcium-dependent protein synthesis of the cells was not detected in culture, neither on the plastic plate nor the type I collagen-coated plate. Moreover, in culture on a type I collagen-coated filter, the size of basal cells was unchanged for 2 d. This should be consistent with the fact that morphological changes in cells are very gradual in vivo. On the other hand, when basal cells were cultured either on a plastic plate or collagen-coated plate, the cells lost their normality; they were markedly enlarged for 2d of culture. Thus, the responses of skin basal cells to extracellular calcium fluctuated according to the types of culture matrixes. In this case, keratin synthesis and a morphological change of the cells seems to be concerned with the clearance, which was established in the basal side of the cultured basal cells as intact skin.

Animals↗

PubMed1995

Cerebrospinal fluid corticotropin-releasing hormone in neurodegenerative diseases: reduction in spinocerebellar degeneration.

Levels of corticotropin-releasing hormone (CRH) in cerebrospinal fluid (CSF) were examined in patients with spinocerebellar degeneration (SCD) including olivopontocerebellar atrophy (OPCA), dentatorubropallidoluysian atrophy (DRPLA) and Friedreich's ataxia, Parkinson's disease (PD) and senile dementia of the Alzheimer type (SDAT), and normal aged subjects. CRH concentrations in CSF were significantly reduced in SCD compared to SDAT, PD and CSF and normal aged subjects. It is likely that degeneration not only of the cerebral cortex and the limbic system but also of the subcortical structures such as the brainstem and the cerebellum alters levels of CRH in CSF. Together with the recent anatomical and physiological evidence, the results suggest pathophysiological relevance of CRH for the cerebellar symptoms in SCD.

Adult↗

PubMed1995

Enzyme-linked immunosorbent assay of pro-gastrin-releasing peptide for small cell lung cancer patients in comparison with neuron-specific enolase measurement.

Our previous study demonstrated that pro-gastrin-releasing peptide(31-98), or ProGRP, is a specific tumor marker in patients with small cell lung carcinoma (SCLC). Using a newly developed, highly sensitive enzyme-linked immunosorbent assay (ELISA) for ProGRP, we analyzed 1,446 samples including those obtained from 478 lung cancer patients to evaluate the clinical usefulness of this ELISA. Several properties indicated that ProGRP is a useful tumor marker for SCLC. First, ProGRP was specifically elevated in SCLC patients. In non-SCLC patients and patients with non-tumorous lung diseases, its serum level was very rarely elevated. Secondly, ProGRP was a reliable marker, in terms of the marked elevation of serum ProGRP levels in SCLC patients. Thirdly, serum ProGRP levels were elevated in SCLC patients even at a relatively early stage of this disease. Fourthly, changes in the serum ProGRP level showed an excellent correlation with the therapeutic responses in SCLC patients. Neuron-specific enolase (NSE) is accepted as a tumor marker of SCLC patients. With the aim of comparing ProGRP and NSE as tumor markers for SCLC patients, we measured serum NSE levels in all samples collected in the present study. We found that ProGRP was superior to NSE in terms of sensitivity, specificity and reliability. Therefore, we consider that ProGRP can play a major role as a clinical tumor marker for SCLC patients.

Biomarkers, Tumor↗

PubMed1995

Cu, Zn superoxide dismutase in patients with dementia of the Alzheimer type.

Cu, Zn superoxide dismutase (SOD) levels in the serum, cerebrospinal fluid (CSF) and skin fibroblasts of patients with dementia of the Alzheimer type (DAT) were estimated using enzyme immunoassay. The SOD mRNA level in the skin fibroblasts was also determined by the Northern blot analysis. As compared with the age-matched control groups of neurological patients without dementia, the AD group consisting of patients with DAT at ages under 65 years of age as well as the SDAT group of patients with DAT at ages over 65 years of age showed no significant changes in serum or CSF SOD levels. However, the skin fibroblast SOD- and SOD mRNA levels, which were correlate each other, were significantly higher in the AD group (p < 0.05), while lower in the SDAT group (p < 0.05). These results suggest that the determination of the SOD level of skin fibroblast may be useful for diagnosis of DAT and that the abnormality of SOD may play an important role in developing DAT.

Alzheimer Disease↗

PubMed1995

Enzyme immunoassay of immunoreactive progastrin-releasing peptide(31-98) as tumor marker for small-cell lung carcinoma: development and evaluation.

Previously, using recombinant human progastrin-releasing peptide (ProGRP)(31-98), we developed a RIA for ProGRP(31-98) and demonstrated that the determination of serum ProGRP(31-98) was a reliable marker for small-cell lung carcinoma (SCLC) (Miyake et al., Cancer Res 1994;54:2136-40). Aiming for a more convenient assay system, we have now developed and evaluated a highly sensitive and specific ELISA for ProGRP(31-98). Only 50 microL of nonextracted serum is needed, and results are obtained in only 2 h. Intraassay and between-day CVs were 1.7-4.6% and 4.2-6.8%, respectively. The log-log calibration curve was linear to 1000 ng/L, and analytical recovery was 91.5-108.7%. The detection limit of this assay, 1.9 ng/L, means that basal concentrations of ProGRP(31-98) were detectable in all healthy subjects. The cutoff value, based on the mean + 3 SD of concentrations in 247 healthy subjects, was set to 45.1 ng/L. Serum concentrations exceeded this value in 18 of 25 SCLC patients, similar to the frequency of increased values found by RIA previously. In contrast, the frequency of increased serum ProGRP(31-98) in patients with nonmalignant pulmonary diseases or non-SCLC was quite low: 0% and 5.0%, respectively. Such results may justify a clinical trial for evaluating this ELISA for the diagnosis and monitoring of SCLC patients.

Amino Acid Sequence↗

PubMed1995

Distribution of event-related potentials in patients with dementia.

Distributions of the amplitudes and the latencies of N100, P200, N200, P300 and mismatch negativity (MMN) were studied. The P300 latency was delayed in patients with dementia of the Alzheimer type (DAT) and patients with vascular dementia (VD). The N200 latency was delayed on Pz in DAT patients, and on Fz in VD patients. MMN latency was delayed on Pz in DAT patients. The P300 amplitude was low on Pz in DAT patients. The N100 amplitude was low in VD patients on Pz. These findings show the difference in cerebral lesions between DAT and VD. We suggest that studies of P300 amplitude, N200 latency, MMN latency and N100 amplitude distribution would be useful in differential diagnosis in patients with dementia.

Aged↗

PubMed1994

Platelet superoxide dismutase in migraine and tension-type headache.

Superoxide dismutase (SOD) is a radical-scavenging enzyme. We determined Cu, Zn-SOD concentrations and activities in platelets from subjects with migraine and tension-type headaches. Thirty migraine without aura (MWoA) patients, 9 migraine with aura (MWA) patients, and 53 tension-type headache patients were selected for study. Thirty healthy volunteers composed the control group. Concentrations of platelet SOD were determined using enzyme-linked immunosorbent assay techniques. The activity of platelet SOD was determined by measuring reductivity of nitroblue tetrazolium. Low concentrations of platelet SOD were found in patients with MWA and MWoA. Platelet SOD activity decreased in MWA patients but not in patients with MWoA or tension-type headaches. These findings suggest vulnerability to oxidative stress in patients with migraine. It is suggested that low platelet SOD levels may play an important role in the etiology of migraine.

Adult↗

PubMed1994

Amyloid beta protein precursor with Kunitz-type protease inhibitor domains (APPI) in cerebrospinal fluid and APPI mRNAs in cultured skin fibroblasts of patients with Alzheimer's disease.

We studied amyloid beta protein precursor with Kunitz-type protease inhibitor domains (APPI) concentration in cerebrospinal fluid (CSF) and APPI mRNA in skin fibroblast in Alzheimer's disease (AD). The subjects consisted of AD, cerebrovascular dementia (VD) and age-matched controls. We measured the APPI concentration in the CSF by the trypsin antibody sandwich ELISA. APPI mRNA was examined by the RT-PCR technique. The CSF APPI concentration in AD was significantly higher than that of VD and controls. The CSF APPI concentration in AD was high in the initial stage of dementia and decreased during the course. The expression of APPI mRNA in skin fibroblasts in AD was also significantly higher than that of VD and controls. These results suggest that measurements of APPI levels in CSF and APPI mRNA in skin fibroblasts may be useful for early diagnosis of AD.

Aged↗

PubMed1993

Clinical effect of WEB 1881 (nebracetam fumarate) on patients with dementia of the Alzheimer type and study of its clinical pharmacology.

We administrated WEB 1881, 800 mg/day (400 mg twice a day), nine patients with dementia of the Alzheimer type for 8 weeks, and undertook an open study to investigate the clinical effects of the distribution into the cerebrospinal fluid (CSF) as well as the influence on the neurotransmitter-related substances in the CSF. These were outpatients living at home with caregivers. Significant clinical improvement was shown by means of the Gottfries, Bråne, and Steen Scale and by Hasegawa's dementia scale. Unchanged WEB 1881 was identified in the CSF. The mean concentration of which was 198.7 ng/ml, this corresponded to 19.0% of the plasma concentration. Of several neurotransmitter-related substances measured in the CSF, a marked rise of AChE activity was observed. Adverse effects consisted of a slight skin eruption in one case and alterations in a clinical laboratory test in another case. These were, however, not significant from a clinical viewpoint. It is suggested that the mechanisms of action of WEB 1881 are based on its transit into the CSF as well as the activation of intracerebral acetylcholinergic systems.

Aged↗

PubMed1993

[Effect of folic acid for treatment of homocystinuria due to 5,10-methylenetetrahydrofolate reductase deficiency].

Deficiency of 5,10-methylenetetrahydrofolate reductase (MTHFR) leads to deficient remethylation of homocysteine and is one of the causes of homocystinuria. Only 28 patients have been reported so far. A 15-year-old boy with mild mental retardation was admitted in our hospital because of progressive difficulty in walking. He is the second child. The paternal grandparents are first cousins. On admission, clinical examination revealed mild disturbance of consciousness, left hemiparesis, truncal ataxia, pyramidal tract signs in the lower limbs and sensory disturbance in his feet. There was no marfanoid symptoms nor ectopia lentis. EEGs showed slow activity with sporadic spike and wave complexes. Peak latencies of N20 of median nerves SEPs, the third and 5th wave of ABR and P100 of VEP were delayed. The CT scan showed mild cortical atrophy and MRI revealed increased intensity on T2-weighted images in the cerebral white matter. Biochemical studies revealed homocystinuria with homocystinemia. Both plasma methionine and serum folic acid were low. Serum vitamin B12 and methylmalonic acid in urine were normal. The lymphoblastoid cell line, transformed by Epstein-Barr virus of lymphocytes of the patient, could not grow when homocysteine was substituted in the culture medium for methionine. The normal control cell line grew naturally under the same condition. A diagnosis of homocystinuria due to MTHFR deficiency was made. The patient was on various therapeutic regimens for about 70 days. Treatment with high doses of folic acid (400 mg/day) resulted in disappearance of homocysteine in plasma, remarkable decrease of homocysteine in urine and increase of methionine in plasma of the patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1992

Decreased superoxide dismutase activity in erythrocyte in Parkinson's disease.

Superoxide dismutase (SOD) activities in Parkinson's disease (PD) were significantly lower than those in controls, especially in a treated PD group. However, SOD activities in an untreated PD group did not decrease. There was a significant correlation between SOD activities and the duration of illness in the treated PD group (p < 0.05). There was a significant correlation between SOD activities and the present doses of L-DOPA/carbidopa in the treated PD group.

Aged↗

PubMed1992

Amyloid beta protein precursors with kunitz-type inhibitor domains and acetylcholinesterase in cerebrospinal fluid from patients with dementia of the Alzheimer type.

We used the ELISA to measure the concentration of amyloid protein precursor with Kunitz type trypsin inhibitor domains (APPI) in CSF of dementia of the Alzheimer type (DAT) and examined the correlation of APPI with acetylcholinesterase (AChE) and somatostatin (SRIF). We found the APPI concentration in CSF of DAT to be significantly elevated compared with that of multi-infarct dementia and controls. We could significantly correlate APPI with AChE, but not correlate APPI with SRIF. The present results suggest that measurement of CSF APPI levels may be useful for diagnosis of DAT and the change of APPI may closely be associated with abnormality of acetylcholine system in DAT that has been reported.

Acetylcholinesterase↗

PubMed1991

Inhibitory effect of 8-chloro-cyclic adenosine 3',5'-monophosphate on cell growth of gastric carcinoma cell lines.

A cAMP analogue, 8-chloro-cAMP (8-Cl-cAMP), selectively binds to site 1 receptor of type II regulatory subunit (RII) of cAMP-dependent protein kinase. The effects of 8-Cl-cAMP on human gastric carcinoma cell lines were studied. Twenty microM 8-Cl-cAMP clearly inhibited cell growth in six cell lines (TMK-1, KATO-III, MKN-7, -28, -45, and -74) but not in MKN-1. Cell population in the G1 phase was increased in KATO III cells, which were more responsive to 8-Cl-cAMP, while cell cycle progression in TMK-1 and MKN-1 cells was apparently not influenced by 8-Cl-cAMP. The various changes induced by 8-Cl-cAMP were further analyzed in TMK-1 cells. Decrease of type I regulatory subunit (RI) of cAMP-dependent protein kinase and translocation of RII from cytosol to nucleus were induced by 8-Cl-cAMP treatment. 8-Cl-cAMP increased the level of cAMP-response element (CRE) binding protein in addition to inducing FOS mRNA, whose promoter contains CRE. 8-Cl-cAMP decreased the expression of mRNA for transforming growth factor-alpha (TGF-alpha), while the expression of epidermal growth factor receptor was not changed. Expression of HRAS and MYC mRNAs was slightly increased, whereas the amounts of HRAS and MYC proteins remained unchanged. Our results overall suggest that 8-Cl-cAMP might be a useful tool for antitumor therapy of gastric cancers and that cell growth inhibition by 8-Cl-cAMP might account for the decrease of TGF-alpha expression by tumor cells.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1990

High-performance liquid chromatography with chemiluminescence detection of serum levels of pre-column derivatized fluoropyrimidine compounds.

7-(Diethylamino)-3-[4-[iodoacetyl)amino)phenyl]-4-methylcoumarin (DCIA) and 4-(bromomethyl)-7-methoxycoumarin have been evaluated as fluoropyrimidine-derivatizing agents to be detected using peroxyoxalate chemiluminescence with high-performance liquid chromatography. The derivatization procedure required only one step. No chemiluminescence was observed from the bromo derivatives, and the detection limits of fluoropyrimidine compounds derivatized with the iodo compound and detected with peroxyoxalate chemiluminescence were in the low femtomole range.

Chromatography, High Pressure Liquid↗

PubMed1990

The threshold of pain and neurotransmitter's change on pain in Parkinson's disease.

Among Parkinson's disease (PD) patients complaining of pain, 10 with pain not associated with a motor fluctuation or L-dopa therapy were evaluated. The controls were 14 PD without pain and eight with thalamic pain syndrome. The threshold of pain and neurotransmitters in CSF were measured in the three groups. In PD with pain, the maximum tolerance level and tourniquet pain ratio decreased significantly. In PD with pain, the score on the self-depression scale increased significantly and 5-hydroxy-indole acetic acid (5-HIAA) among the neurotransmitters decreased significantly. These results suggest that decreases in the threshold of pain and changes of serotonin in CSF are involved in the development of specific pain in PD who do not respond to L-dopa.

Aged↗