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Biomedical subjects

T Saitoh

Publications and source records attributed to T Saitoh.

At least 145 records · Page 8Linked to original sources
PubMed1998

Association of CYP2D microsatellite polymorphism with Lewy body variant of Alzheimer's disease.

OBJECTIVE: To examine the genetic association of CYP2D6 locus with Lewy body variant (LBV) and Parkinson's disease (PD). METHODS: Allelic association was studied in patients with pure AD, LBV, and PD by using the CYP2D microsatellite, the (dG-dT)n dinucleotide repeat (n=16 to 27) located between CYP2D8P and CYP2D7 genes, and the CYP2D6 B and D mutations. RESULTS: We found overrepresentation of the alleles longer than 21 repeat (the long-type alleles) in LBV (allele frequency, 0.313) (odds ratio=1.99, p=0.019 by chi2 test) and in PD (0.298) (odds ratio=1.86, p=0.037), but not in pure AD (0.196), compared with the age-matched control (0.186). Strong association was noted of the long-type alleles with the CYP2D6 B mutation (odds ratio=88.50, p < 0.001 by Fisher's exact test), but not with the D mutation or the deletion of CYP2D6 gene. CONCLUSIONS: The CYP2D locus is closely associated with LBV and PD. The CYP2D6 B mutation may be involved in pathogenesis of LBV and PD in a dominant-negative manner, or in the linkage disequilibrium of the CYP2D microsatellite to another pathogenic gene locus.

Aged↗
PubMed1998

Relationship between normalization of negative T waves on exercise ECG and residual myocardial viability in patients with previous myocardial infarction and no post-infarction angina.

The usefulness of normalization of negative T waves in exercise ECG was investigated as an index of myocardial viability in patients with previous myocardial infarction with no symptoms or ischemic ST-segment change during exercise test. A total of 39 patients, 20 with T-wave normalization (POS group) and 19 without T-wave normalization (NEG group) on exercise ECG. were studied. Myocardial viability was evaluated by thallium-201 single-photon emission computed tomography (SPECT) during exercise or at rest. We also assessed left ventricular ejection fraction (LVEF) by contrast ventriculography before (n=39) and after percutaneous transluminal coronary angioplasty (PTCA) (n=17). SPECT detected myocardial viability in 16 (80%) of the 20 patients in the POS group and in 4 (21%) of the 19 patients in the NEG group (p<0.01). LVEF increased after successful PTCA in the POS group (from 53+/-13% to 63+/-8%, p<0.025), but fell in the NEG group (from 57+/-10% to 51+/-8%). It is concluded that normalization of negative T waves on exercise ECG is a useful, simple index of myocardial viability in patients with previous myocardial infarction with no symptoms or ischemic ST-segment change during exercise testing.

Adult↗
PubMed1998

Coronary hyperreactivity to adrenergic stimulation and increased nocturnal vagal tone trigger coronary vasospasm.

The relationship between autonomic nervous system activity (ANA) and coronary vasoreactivity during transient myocardial ischemia was determined in patients with vasospastic angina (VA). ANA was measured by power spectral analysis of heart rate variability and humoral factors following intravenous infusion of insulin in 24 patients with VA and 6 control patients. Nine (38%) of the VA patients had significant ST segment depression (STD), and 4 of these patients had symptomatic STD. The frequency of anginal episodes in the 9 patients with VA and STD was significantly greater than that in the 15 VA patients without STD (3.4 +/- 3.1 vs 0.5 +/- 0.8 episodes/week, p < 0.05). The increase in the LF/HF ratio 30 min after insulin injection in patients with STD was significantly greater than that in patients without STD (34 +/- 31% vs 4 +/- 34%, p < 0.05). All of the patients with VA and STD had significant coronary vasospasm in response to the infusion of < or = 20 micrograms of acetylcholine, higher levels of nocturnal parasympathetic activity, and greater norepinephrine production in response to insulin stimulation than the VA patients without STD. These findings suggest that increased vagal tone and hyperreactivity to adrenergic stimulation may trigger vasospasm in patients with VA.

Aged↗
PubMed1998

Protection against glutamate neurotoxicity in retinal cultures by acidic conditions.

We evaluated the effects of extracellular acidic conditions on glutamate-induced death in cultured retinal neurons. Primary retinal cultures, obtained from 3- to 5-day-old Wistar rats, were estimated to be consisted of mainly amacrine cells (90%) together with a small population of horizontal (8%) and ganglion cells (2%). We examined the effects of acidic pH (pH 6.0 to 7.0) on glutamate neurotoxicity by monitoring the delayed death of retinal neurons induced by brief (10 min) exposure to 1 mM glutamate followed by a 24-hr incubation. The glutamate-induced delayed death of cultured retinal neurons was attenuated with an acidic pH between 6.0 and 7.0. Furthermore, whole-cell patch-clamp recordings were taken from retinal neurons to examine the effects of acidic pH on N-methyl-D-aspartate (NMDA) or kainate receptor-mediated currents. NMDA- and kainate-induced currents were suppressed at pH 6.0 to 7.0 and pH 6.0 to 6.5, respectively. The acidity of the medium protected the retinal neurons from glutamate-induced delayed death, probably by inhibiting NMDA and/or kainate receptor activation.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1998

Alanine dehydrogenase from Enterobacter aerogenes: purification, characterization, and primary structure.

Alanine dehydrogenase [EC 1. 4. 1. 1] was purified to homogeneity from a crude extract of Enterobacter aerogenes ICR 0220. The enzyme had a molecular mass of about 245 kDa and consisted of six identical subunits. The enzyme showed maximal activity at about pH 10.9 for the deamination of L-alanine and at about pH 8.7 for the amination of pyruvate. The enzyme required NAD+ as a coenzyme. Analogs of NAD+, deamino-NAD+ and nicotinamide guanine dinucleotide served as coenzymes. Initial-velocity and product inhibition studies suggested that the deamination of L-alanine proceeded through a sequential ordered binary-ternary mechanism. NAD+ bound first to the enzyme, followed by L-alanine, and the products were released in the order of ammonia, pyruvate, and NADH. The Km were 0.47 mM for L-alanine, 0.16 mM for NAD+, 0.22 mM for pyruvate, 0.067 mM for NADH, and 66.7 mM for ammonia. The Km for L-alanine was the smallest in the alanine dehydrogenases studied so far. The enzyme gene was cloned into Escherichia coli JM109 cells and the nucleotides were sequenced. The deduced amino acid sequence was very similar to that of the alanine dehydrogenase from Bacillus subtilis. However, the Enterobacter enzyme has no cysteine residue. In this respect, the Enterobacter enzyme is different from other alanine dehydrogenases.

Alanine Dehydrogenase↗
PubMed1998

Usefulness of exercise thallium-201 imaging in evaluation of low- and high-risk groups in coronary artery disease patients with disappearance of anginal episodes by anti-anginal drug therapy.

Our objective was to clarify the management of patients with silent myocardial ischemia (SMI) and documented coronary artery disease. We evaluated 222 such patients who did not develop anginal pain during exercise thallium-201 imaging (ST-TL). They were divided into low- and high-risk groups based on results of left ventriculographic findings at rest, ST-TL, and coronary angiography. The incidence of cardiac events was 28/222 (13%) overall, being 9 of 110 (8%) in the low-risk patients, and 19 of 112 (17%) in the high-risk group. Kaplan-Meier survival analysis revealed a significant difference between the two groups (p = 0.020). Analysis of the survival of the high-risk group revealed significant differences between the patients with a negative and positive redistribution (p = 0.047), but such differences were not significant in the low-risk patients. Therefore, the classification of SMI patients into low- and high-risk categories was an appropriate strategy. ST-TL was useful for identifying patients with myocardial ischemia and selecting those to receive coronary revascularization and/or drug therapy.

Adrenergic beta-Antagonists↗
PubMed1998

[Plasma cell leukemia (IgG kappa) presenting bilateral neurosensory hearing loss and left sixth cranial nerve plasy].

A 30-year-old man who had been given a diagnosis of IgG-kappa multiple myeloma by another hospital and treated with melphalan, prednisone, and cyclophosphamide 6 months earlier, was admitted to our hospitaly in July 1994 because of progressively impaired hearing in both ears, vertigo, and worsening fatigue. Peripheral blood examination showed a white blood cell count 25,000/microliter, with 77.5% atypical plasma cells. Examination at the time of hospitalization also revealed retinal hemorrhages and serum hyperviscosity. The diagnosis was plasma cell leukemia with hyperviscosity syndrome. Subsequent treatment consisted of vincristine, doxorubicine, and prednisone and repeated plasmapheresis. This resulted in a partial response and a reduction of serum viscosity but no reversal of hearing loss. One month after admission, left sixth cranial nerve plasy was demonstrated. Cranial computed tomography studies disclosed a tumoral mass in the sphenoid sinus. The patient received local radiotherapy and intensive chemotherapy, but exhibited no notable alleviation of his cranial nerve palsy. He died of septicemia and progressive disease in August 1994. This case was rare in that it involved plasma cell leukemia and bilateral neurosensory hearing loss associated with serum hyperviscosity and sixth cranial nerve plasy due to plasmacytoma within the sphenoid sinus.

Abducens Nerve↗
PubMed1998

[Diagnosis for human parvovirus B19-polyarthritis: usefulness of empty particle B19.ELISA and B19-DNA.PCR].

OBJECTIVE: To evaluate the usefulness of new ELISA for human parvovirus B19 (B19) antibodies and PCR for the diagnosis of acute onset of B19 polyarthritis. METHODS: We evaluated the reproducibility and sensitivity on the detection of anti-B19 antibody by ELISA using recombinant VP-1 and VP-2 (empty particle), and then studied for the prevalence of IgM and IgG B19 antibody in 125 samples for anti-B19 tests. The random study on anti-B19 antibody assay as well as PCR for B19-DNA was also performed in 130 cases with acute onset of arthritis excluding those with known origins, 224 with rheumatoid arthritis and 149 with other categories. RESULTS: The results by using B19-empty particle ELISA were reproducible and showed the assay was a sensitive way for clinical use. IgM anti-B19 antibodies were positive not only in all samples from erythema infectiosum, but also often in those from hemolytic anemia, pure red cell aplasia, fetal hydrops, hepatic injury, fever of unknown origin. Among 130 with acute onset of arthritis, 21 showed positive tests for IgM anti-B19 antibody and/or B19 DNA. On the other hand, 4 among 224 patients with rheumatoid arthritis were positive for IgM anti-B19 antibody, but all of 149 in control group were negative for IgM anti-B19 antibodies and for B19 DNA. CONCLUSION AND DISCUSSION: Anti-B19 ELISA using B19-empty particle which has been introduced as a routine test system, is a useful tool for the diagnosis of acute onset of B19 arthritis. An additional examination using PCR for B19 DNA may contribute for understanding persistent B19 polyarthritis or reactivation of B19 infection.

Adolescent↗
PubMed1997

Study of in vitro cytotoxicity of a water soluble organic arsenic compound, arsenosugar, in seaweed.

In the present study, we demonstrated the cytotoxic effect of a dimethylarsenic compound in seaweed, (R)-(2',3'-dihydroxypropyl) 5- deoxy-5-dimethylarsinoyl-beta-D-riboside, namely arsenosugar (AsSug), on mammalian cells, murine macrophages, in comparison with that of an inorganic arsenical, arsenite, in vitro. More than 99.5% pure AsSug was synthesized. Arsenite was strongly and equally toxic to both peritoneal macrophages (PMs) and alveolar macrophages (AMs), and the concentration of arsenite that inhibited the viability of cells by 50% compared to the viability of control cells (50% inhibitory concentration; IC50) was 5 microM. In contrast, AsSug showed no cytotoxicity to both PMs and AMs at the microM concentration level; however, it induced different and interesting cellular responses in both macrophages at high concentrations, 1-10 mM. AsSug enhanced the viability of PMs at an optimal dose of 5 mM; conversely, it showed weak but significant cytotoxicity to AMs (IC50 = 8 mM).

Animals↗
PubMed1997

Amyloid precursor protein activates phosphotyrosine signaling pathway.

Amyloid precursor protein (APP) is known to have neurotrophic effects but little information is available on the signaling pathways activated by APP. Since neurotrophic factors activate tyrosine phosphorylation signaling pathway in general, we investigated whether or not APP activates tyrosine phosphorylation pathway. Alpha-secretase derived APP (sAPP alpha) increased the number of neurites per cell and enhanced tyrosine phosphorylation levels on distinct 125 and 200 kDa protein bands. The APP3 19-335 17-mer peptide, which has been reported to be responsible for the neurotrophic effect of sAPP alpha [Jin, L.-W., Ninomiya, H., Roch, J.-M., Schubert, D., Masliah, E., Otero, D.A.C. and Saitoh, T., J. Neurosci., 14 (1994) 5461-5470], increased neurite extension as well as tyrosine phosphorylation on 125 and 200 kDa proteins in a similar manner to sAPP alpha. Both effects were blocked by an antagonist peptide to 17-mer ERMSQ (APP329-333). These results indicate that the 17-mer domain of APP induces tyrosine phosphorylation on distinct proteins under the condition that induces neurite extension.

Amyloid Precursor Protein Secretases↗
PubMed1997

Reversible ischemia increases levels of Alzheimer amyloid protein precursor without increasing levels of mRNA in the rabbit spinal cord.

In a rabbit spinal cord ischemia model (RSCIM), the time courses of neuropathological damage of the spinal cord and neurological impairment of the motor functions are well established, demonstrating that the extent of neuropathological damage and the severity of neurological impairment are closely correlated. We used the RSCIM to elucidate the effects of reversible (15 min) and irreversible (60 min) ischemia on the endogenous levels of amyloid protein precursors (APPs) at both the mRNA and protein levels in the caudolumbar/sacral region of the spinal cord. We speculate that endogenous APPs are induced by ischemia as either trophic factors or stress-induced proteins in the RSCIM. A 15-min occlusion transiently increased the APP protein levels in neurons, which returned to the original levels by the end of 60 min occlusion. The increase in APP protein levels during 15-min ischemic insult does not appear to involve regulation at the mRNA level. The increased level of APPs, particularly of the soluble form, could support the possibility that APPs play a neuroprotective role in the RSCIM as stress-induced proteins. In contrast, failure to maintain the increased APP protein levels or to increase the mRNA, as seen in the 60-min ischemia samples, may be one of the causal factors that induce necrosis and neuronal cell death leading to irreversible neurological impairment.

Amyloid beta-Protein Precursor↗
PubMed1997

NACP, a synaptic protein involved in Alzheimer's disease, is differentially regulated during megakaryocyte differentiation.

Non-amyloid-beta component precursor (NACP) is a presynaptic protein which may play a role in amyloidogenesis in Alzheimer's disease (AD). Since an abnormal function of platelets has been demonstrated in AD, platelets could be used as a model to investigate the role of NACP in this disease. We characterized the patterns of NACP and beta-synuclein expression in a megakaryocyte-platelet system (K562). In this hematopoietic cell line, NACP expression was up-regulated during phorbol ester-induced megakaryocytic differentiation, while beta-synuclein was down-regulated. Consistent with this, NACP but not beta-synuclein was abundantly expressed in platelets. Immunogold electron microscopy of platelets showed that NACP is loosely associated with the plasma membrane, the endomembrane system and, occasionally, with the membrane of secretory alpha-granules. These findings suggest that coordinate expression of the synuclein family members may play a critical role during hematopoietic cell differentiation. Additionally, expression of the synuclein family members may be developmentally regulated during neural differentiation.

Amyloid↗
PubMed1997

Role of the C terminus in histamine H2 receptor signaling, desensitization, and agonist-induced internalization.

To evaluate the role of the histamine H2 receptor C terminus in signaling, desensitization, and agonist-induced internalization, canine H2 receptors with truncated C termini were generated. Wild-type (WT) and truncated receptors were tagged at their N termini with a hemagglutinin (HA) epitope and expressed in COS7 cells. Most of the C-terminal intracellular tail could be truncated (51 of 70 residues, termed T308 mutant) without loss of functions: cAMP production, tiotidine binding, and plasma membrane targeting. In fact, the T308 mutant produced more cAMP than the WT when cell-surface expression per cell was equivalent. Pretreatment of cells with 10(-5) M histamine desensitized cAMP productions via WT and T308 receptors to similar extents. Incubation of cells expressing WT receptors with 10(-5) M histamine reduced cell-surface anti-HA antibody binding by approximately 30% (by 30 min, t1/2 approximately 15 min), but did not affect the Bmax of tiotidine in membrane fractions, which represents total receptor amounts, suggesting that WT receptors were internalized from the cell surface. In contrast, no internalization was observed with T308 receptors following histamine treatment. A mutant with a deletion of the 30 C-terminal amino acids, termed T329, was functional but was as potent as the WT in terms of cAMP production. Apart from being desensitized by histamine, the internalization of the receptor was indistinguishable from that of the WT. Internalization was observed in the T320 but not in T313 mutant, narrowing the region involved in internalization to that between Glu314 and Asn320 (ETSLRSN). Of these seven residues, either Thr315, Ser316, or both, were replaced with Ala. Thr315 and Ser316 are conserved among species. The mutation at Thr315 (but not that at Ser316) abolished internalization. Taken together, these results demonstrate that Thr315 is involved in agonist-induced internalization. Furthermore, the finding that T308 receptors were desensitized in the absence of internalization suggests that internalization and desensitization are meditated by independent mechanisms.

Amino Acid Sequence↗
PubMed1997

Oligomer formation of histamine H2 receptors expressed in Sf9 and COS7 cells.

A histamine H2 receptor, which had been mutated at its glycosylation site and tagged at its N-terminus with an HA tag (HA-H2 receptor), was expressed in Sf9 cells and COS7 cells. Immunoprecipitation and immunoblotting of HA-H2 receptors with alphaHA antibody revealed four bands of 31.5 +/- 2.5 kDa, 59.0 +/- 6.0 kDa, 80.5 +/- 4.5 kDa and 120 kDa. These bands were also detected by immunoblot using anti-H2 receptor serum (C-terminus). In addition, H2 receptors without the HA-tag coimmunoprecipitated with HA-tagged H2 receptors devoid of the 51 C-terminal amino acids, via immunoprecipitation with alphaHA antibody, when the two receptors were coexpressed. These results suggest that H2 receptors are present as receptor oligomers and that the C-terminal portion is not involved in the formation of these oligomers.

Animals↗
PubMed1997

Neurodegeneration and cognitive impairment in apoE-deficient mice is ameliorated by infusion of recombinant apoE.

Recent studies suggest that apolipoprotein E (apoE) might play a neurotrophic function in the central nervous system and that altered functioning of this molecule could result in neurodegeneration. The main objective of this study was to determine if neurodegenerative and cognitive alterations in apoE-deficient mice are reversible by infusion of recombinant apoE into the lateral ventricles. ApoE-deficient mice treated with either apoE3 or apoE4 showed a significant improvement in their learning capacity in the Morris water maze compared to saline-infused apoE-deficient mice. While this improved performance was associated with restoration of neuronal structure, the poor learning ability of apoE-deficient mice treated with saline correlated with the disrupted synapto-dendritic structure. This study supports the contention that apoE might play a neurotrophic effect in vivo and suggests that apoE might have a potential therapeutic role.

Animals↗
PubMed1997

Immunological abnormalities in splenic marginal zone cell lymphoma.

The clinical features of patients with splenic marginal zone cell lymphoma (SMZCL) have rarely been reported. In the present study, immunological abnormalities, particularly hematological abnormalities, observed in SMZCL were described. Autoimmune hemolytic anemia, immune thrombocytopenia, and appearance of lupus anticoagulant were observed in 2 of 3 patients with SMZCL. Other abnormal data including monoclonal gammopathy and cold agglutinin were also observed in 2 of the 3 patients. Immunological abnormalities may be characteristic complications in patients with SMZCL and must be followed carefully, since they may be a reliable marker of this type of lymphoma activity.

Aged↗
PubMed1997

Genetic evidence for the involvement of tau in progressive supranuclear palsy.

A dinucleotide repeat polymorphism in a tau intron was identified and used in a case-control study to analyze the genetic association of tau with several neurodegenerative diseases with tau pathology. Subjects with the homozygous tau AO alleles were excessively represented in the progressive supranuclear palsy (PSP) group, compared with the age-matched healthy control group. Consequently, this allele is more frequently found in PSP than in a group of healthy subjects. This trend was not found in Alzheimer's disease or parkinsonism-dementia complex of Guam, both of which are accompanied by major tau pathology. The result suggests a possible involvement of tau in the pathogenesis of PSP.

Base Sequence↗