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Biomedical subjects

K Urakami

Publications and source records attributed to K Urakami.

At least 37 records · Page 2Linked to original sources
PubMed1999

Phosphorylated tau in human cerebrospinal fluid is a diagnostic marker for Alzheimer's disease.

Microtubule-associated protein tau in cerebrospinal fluid (CSF) has been proposed as a diagnostic marker for Alzheimer's disease (AD), but there is overlap between AD patients and non-AD controls. To improve the diagnostic accuracy, we measured phosphorylated tau in CSF, because phosphorylated tau accumulates as pathological paired helical filaments in neurons of the AD brain. Immunoblot showed that CSF contained a 32 kDa N-terminal fragment of tau that was partially phosphorylated on Ser199, Thr231 and Ser235. A sandwich enzyme immunoassay revealed that phosphorylated CSF-tau levels were significantly higher in AD patients than those in non-AD controls. Discrimination between the two groups was clearer in phosphorylated CSF-tau than in total CSF-tau. The data indicate that elevated phosphorylated CSF-tau level is a more specific diagnostic marker for AD.

Alzheimer Disease↗
PubMed1999

Apolipoprotein E4 accelerates dementia and increases cerebrospinal fluid tau levels in Alzheimer's disease.

To examine the effect of apolipoprotein E (ApoE) 4 on the progression of Alzheimer's disease (AD), the clinical course of 33 AD patients (17 cases with ApoE epsilon4 and 16 cases without ApoE epsilon4) was evaluated with the mini-mental state examination (MMSE) and cerebrospinal fluid (CSF) biological markers. The decline of MMSE scores to zero was shortened in the ApoE4 group. During a mean follow-up of 20 months, a significant increase of CSF tau levels was observed in the ApoE4 group. A lower level of CSF A beta1-42(43) was found in both the ApoE4 and non-ApoE4 groups than in age-matched normal controls. The ApoE epsilon4 allele accelerates the progression of dementia and increases the levels of CSF tau in AD patients.

Aged↗
PubMed1999

Immunohistochemical determination of the Wilson Copper-transporting P-type ATPase in the brain tissues of the rat.

Immunohistochemical localization of Copper-transporting P-type ATPase (ATP7B), a gene product responsible for Wilson disease, was visualized in the brain tissues of the Long-Evans agouti rat in detail using tissue-blotting technique and confocal laser microscopy. The ATP7B was intensely detected in neuronal cells of the hippocampal formation, olfactory bulbs, cerebellum, cerebral cortex and nuclei in the brainstem in which high amounts of copper and cuproenzymes, dopamine beta hydroxylase and Cu,Zn-superoxide dismutase (Cu,Zn-SOD) were detected. The present results suggest that ATP7B plays key roles in neurotransmissions of catecholamine pathway and preventing brain tissues from injury by superoxide radicals to regulate the cellular Cu concentration and/or activities of cuproenzymes related to neurotransmissions and a free radical metabolism. Furthermore, it is reasonable to assume that neurotoxicity due to abnormal copper accumulation or irregular regulation of cuproenzymes in the critical brain regions by mutation of the ATP7B gene leads to neurological failures of Wilson disease.

Adenosine Triphosphatases↗
PubMed1999

Germination-specific cortex-lytic enzymes from Clostridium perfringens S40 spores: time of synthesis, precursor structure and regulation of enzymatic activity.

Germination-specific enzymes, an amidase and a muramidase, of Clostridium perfringens S40 were synthesized at the time of forespore formation during sporulation. The amidase had a unique precursor structure consisting of four domains: the N-terminal pre-sequence, the N-terminal pro-sequence, mature enzyme and the C-terminal pro-sequence. The N-terminal pre-sequence and the C-terminal pro-sequence were sequentially processed at the time of development of phase-bright spores, and the resulting inactive pro-enzyme was activated by cleavage of the N-terminal pro-sequence with a specific protease during germination. A possible mechanism for the regulation of activity of muramidase, which is produced as a mature form and does not need processing for activation, is presented.

Amidohydrolases↗
PubMed1999

A comparison of tau protein in cerebrospinal fluid between corticobasal degeneration and progressive supranuclear palsy.

Many clinical and pathological discussions have been focused on the difficulty of differential diagnosis between corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) in recent years. This study was conducted to evaluate the usefulness of tau proteins in cerebrospinal fluid (CSF) for the differentiation of these two diseases. Subjects consisted of 10 patients with CBD (four males and six females with a mean age of 67.9+/-5.8 years), 12 patients with PSP (eight males and four females with a mean age of 62.6+/-5.8 years) and 36 control subjects (CTL) (16 males and 20 females with a mean age of 65.8+/-9.9 years). The CBD group included patients with probable CBD, while all the patients in the PSP group satisfied the diagnostic criteria developed by the National Institute of Neurological Disorders and Stroke and Society for PSP (NINDS-SPSP). CSF tau proteins were measured with the sandwich ELISA method (Innogenetics, Belgium). The CSF tau protein level was 320.1+/-86.5 pg/ml in the CBD group, 151.5+/-52.7 pg/ml in the PSP group and 128.7+/-91.7 pg/ml in the CTL group. Significant differences were noted in tau protein levels between the CBD group and both the PSP group (P<0.001) and the CTL group (P<0.005). We suggested that the measurement of CSF tau proteins may be useful for the differentiation between CBD and PSP.

Aged↗
PubMed1999

Positive association between an estrogen receptor gene polymorphism and Parkinson's disease with dementia.

Parkinson's disease (PD) is a common cause of dementia in the elderly. Dementia in Alzheimer's disease (AD) and PD share common biologic and clinical features. The estrogen receptor (ER) gene is one of the susceptibility genes for AD. In order to test the hypothesis that the overlap between AD and PD may have a genetic basis, we determined ER gene polymorphisms in 13 PD patients with dementia (PDD) (age +/- SD; 71.9 +/- 5.5 years), 71 PD patients without dementia (PDND) (68.4 +/- 7.5 years), 86 AD patients (76.8 +/- 8.0 years) and 51 control subjects (CTL) (74.9 +/- 6.9 years). ER genotypes were classified as a P or p allele on the basis of a Pvu II-RFLP, and X and x on the basis of a Xba I-RFLP. The frequency of the P allele in the PDD group as well as the AD group was higher than that in CTL. There was no significant difference in the distribution of the P allele between CTL and PDND. There were no significant differences in the distribution of the X allele among the PDD, PDND and CTL groups, whereas a higher incidence was found in AD. We conclude that the ER gene may be a common susceptibility gene for dementia in PD as well as AD.

Aged↗
PubMed1999

Alteration in brain presenilin-1 mRNA expression in sporadic Alzheimer's disease.

Expression of presenilin-1 (PS-1) mRNA in an alternative splicing at the 3' end of exon 3 was examined in brain tissue, lymphocytes and cultured skin fibroblasts using the RT- polymerase chain reaction (RT-PCR) method. We quantified the relative ratios of the densities of the long form of PS-1 mRNA, which contains a sequence encoding four amino acids (VRSQ, denoted as VRSQ+) to the short form, which lacks the VRSQ sequence (VRSQ-). The brain tissue of subjects with sporadic Alzheimer's disease (AD) had reduced levels of the VRSQ+ form of the PS-1 mRNA compared to a control group. No significant differences appeared in peripheral tissues, such as lymphocytes or cultured skin fibroblasts in AD with control subjects. Changes in the alternative splicing of exon 3 may be specific to the brain and may play an important role in the pathogenesis of sporadic AD.

Aged↗
PubMed1999

Structural study of PLGA [copoly (DL-lactic/glycolic acid)], a biodegradable polymer for parenteral sustained release preparations, by tandem mass spectrometry.

A copoly (DL-lactic/glycolic acid) (PLGA), with a weight-average molecular weight of about 8400, has been characterized using fast atom bombardment (FAB)-tandem mass spectrometry in order to determine the sequence. Because of the large molecular size, PLGA was partially hydrolyzed and the terminal hydroxyl groups in the resulting oligomer mixture acetylated as the indicator. The FAB spectrum of this sample showed a complex ion signal pattern containing monomer to octamer. Diagnostic product ions containing useful information for sequence determination were observed in collision-induced dissociation-MS/MS and MS/MS/MS of these oligomer ions. The results of analysis for dimers through pentamers showed that they have random sequences of lactic and glycolic acid, suggesting that the whole structure of PLGA also has a random sequence.

Acetylation↗
PubMed1998

Hepatocyte injury in tyrosinemia type 1 is induced by fumarylacetoacetate and is inhibited by caspase inhibitors.

Tyrosinemia type 1, caused by mutations in the fumarylacetoacetate hydrolase gene (Fah), is characterized by severe liver injury. We earlier developed a tyrosinemic mouse model with two genetic defects, Fah and 4-hydroxyphenylpyruvate dioxygenase (Hpd) deficiencies. Apoptosis of hepatocytes was induced and an acute onset of liver failure occurred after administration of homogentisic acid (HGA), the intermediate metabolite between the enzymes HPD and FAH. Cytochrome c was released from mitochondria prior to liver failure in the Fah-/- Hpd-/- double-mutant mice after the administration of HGA. In a cell-free system, the addition of fumarylacetoacetate induced the release of cytochrome c from the mitochondria. We also found that caspase inhibitors were highly effective in preventing the liver failure induced by HGA in the double-mutant mice. Therefore, fumarylacetoacetate apparently induces the release of cytochrome c, which in turn triggers activation of the caspase cascade in hepatocytes of subjects with hereditary tyrosinemia type 1.

Acetoacetates↗
PubMed1998

Longitudinal study of cerebrospinal fluid levels of tau, A beta1-40, and A beta1-42(43) in Alzheimer's disease: a study in Japan.

To clarify the alterations of tau, amyloid beta protein (A beta) 1-40 and A beta1-42(43) in the cerebrospinal fluid (CSF) that accompany normal aging and the progression of Alzheimer's disease (AD), CSF samples of 93 AD patients, 32 longitudinal subjects among these 93 AD patients, 33 patients with non-AD dementia, 56 with other neurological diseases, and 54 normal control subjects from three independent institutes were analyzed by sensitive enzyme-linked immunosorbent assays. Although the tau levels increased with aging, a significant elevation of tau and a correlation between the tau levels and the clinical progression were observed in the AD patients. A significant decrease of the A beta1-42(43) levels and a significant increase of the ratio of A beta1-40 to A beta1-42(43) were observed in the AD patients. The longitudinal AD study showed continuous low A beta1-42(43) levels and an increase of the ratio of A beta1-40 to A beta1-42(43) before the onset of AD. These findings suggest that CSF tau may increase with the clinical progression of dementia and that the alteration of the CSF level of A beta1-42(43) and the ratio of A beta1-40 to A beta1-42(43) may start at early stages in AD. The assays of CSF tau, A beta1-40, and A beta1-42(43) provided efficient diagnostic sensitivity (71%) and specificity (83%) by using the production of tau levels and the ratio of A beta1-40 to A beta1-42(43), and an improvement in sensitivity (to 91%) was obtained in the longitudinal evaluation.

Aged↗
PubMed1998

Apo A-I and apo E concentrations in cerebrospinal fluids of patients with acute meningitis.

It has been demonstrated that apolipoproteins found in cerebrospinal fluid (CSF) play an important role in lipid metabolism in the central nervous system (CNS). Previously we reported that CSF apo A-I levels increased with the severity of neurological damage in poliovirus-infected macaques. In the present study, apo A-I was quantitatively analysed in CSF from patients with or without neurological diseases. In controls, CSF apo A-I level was significantly higher in males; 3.83 (0.40) mg/L, mean (SEM) (n = 19) compared with females, 2.42 (0.26) mg/L (n = 23, P < 0.05). CSF apo A-I concentrations in patients with acute meningitis increased at the active stage, 7.74 (1.78) mg/L (n = 10), but returned to basal concentrations at the convalescent stage 2.72 (0.38) mg/L (n = 10), while the CSF apo A-I level in patients with other neurological diseases remained in the same range as in controls. By contrast, CSF apo E was consistently elevated at either stage of acute meningitis. Furthermore, it was found that the levels of CSF apo A-I, but not of apo E, correlated positively with CSF albumin concentrations. These findings suggest that the CSF apo A-I and apo E have different origins and may play different roles in the lipoprotein metabolism in CNS.

Acute Disease↗
PubMed1998

Basic and clinical studies on ApoE gene typing by line probe assay (LiPA) as a biological marker for Alzheimer's disease and related disorders: multicenter study in Japan.

The fundamental reagent capability and clinical significance of ApoE gene typing has been investigated. The result of each test shows that the reagent capability satisfied the expected standard. Four-hundred thirty-nine samples classified into three groups (Alzheimer's disease (AD), other types of dementia and nondementia) were measured to examine the clinical significance. The rate of epsilon 4 genotype of each group was 31.5%, 14.6%, 10.4%, respectively. The AD group had a higher rate than the other groups (p < 0.001). The measurement of ApoE genotype is suggested to be useful as one of the guidelines in the diagnosis of AD.

Age Factors↗
PubMed1998

Basic and clinical studies on the measurement of tau protein in cerebrospinal fluid as a biological marker for Alzheimer's disease and related disorders: multicenter study in Japan.

The development of a diagnostic marker for earlier and more accurate clinical diagnosis of Alzheimer's disease (AD) is essential to identify AD patients during life unequivocally. The purpose of this study was to investigate the basic performance and clinical significance of tau level measurement in the cerebrospinal fluid (CSF) using an enzyme-linked immunosorbent assay (ELISA) developed by Innogenetics. The ELISA system showed reliable reproducibility and good linearity. For clinical studies, the CSF samples from a variety of patients (n = 332) were examined. They were classified into the four groups: Alzheimer's disease (AD); neurodegenerative disease (ND); cerebrovascular diseases (VD); and a neurological control (NC) group. The CSF-tau levels for AD, ND, VD and NC were 426 +/- 234 pg/ml, 239 +/- 157 pg/ml, 216 +/- 136 pg/ml, and 188 +/- 103 pg/ml, respectively. The CSF-tau level of the AD group was significantly higher than that of the other groups (p < 0.001). The CSF-tau levels increased during follow-up. The measurement of the tau level in CSF is shown to be a useful marker to confirm a clinical diagnosis of AD.

Aged↗
PubMed1997

Cerebrospinal fluid apo E and apo A-I concentrations in early- and late-onset Alzheimer's disease.

We compared cerebrospinal fluid (CSF) apolipoprotein (apo) A-I and apo E concentrations in early- and late-onset Alzheimer's disease (EOAD (n = 11), LOAD (n = 15), respectively) with those in control subjects (n = 23). CSF apo A-I levels in both EOAD and LOAD were consistent with control subjects. However, CSF apo E levels were significantly lower in EOAD group (mean +/- SD; 2.65 +/- 1.69 mg/l, P < 0.05) and higher in LOAD group (5.90 +/- 1.94 mg/l, P < 0.01) than those in control group (4.16 +/- 1.69 mg/l). In addition, the epsilon4 allele frequency was not different between EOAD and LOAD groups. Although the reason for the difference in CSF apo E concentrations between two groups is unknown, CSF apo E concentration seems to be associated with the pathogenesis of EOAD and LOAD. The rate of apo E production and/or catabolism in the brain may be different between them.

Aged↗