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Biomedical subjects

T Saitoh

Publications and source records attributed to T Saitoh.

At least 199 records · Page 11Linked to original sources
PubMed1996

Effect of pulsatile and nonpulsatile assist on heart and kidney microcirculation with cardiogenic shock.

To estimate microcirculation of the heart and kidney in pulsatile and nonpulsatile-assisted circulation, a comparison study was done using a swine model. Acute myocardial infarction was made by ligation of the left coronary artery branches. After cardiogenic shock, animals were divided into 3 groups as follows: Group C (n = 6), no assist provided; Group NP (n = 6), assisted by a nonpulsatile pump (Bio-Medicus BP-80); Group P (n = 6), supported by a pulsatile pump (Nippon Zeon). left coronary artery flow, endocardial and epicardial regional flows, and renal cortex and medulla tissue blood flows were measured. Left coronary artery flow and endocardial and epicardial tissue blood flows decreased in cardiogenic shock, and they recovered to the control level soon after support in both Group N and Group P. Renal medulla and cortex tissue blood flows decreased in cardiogenic shock, and these flows did not recover in either Group N or P. However, cortex blood flow in Group P did improve, but it did not improve in Group N. These results suggested that pulsatile assist was more effective than nonpulsatile assist for microcirculation after cardiogenic shock to avoid deterioration of major organ functions.

Animals↗
PubMed1996

[Importance of timing for radiation therapy in limited-stage small cell lung cancer].

We defined one group of patients who underwent radiotherapy within 75 days from the beginning of treatment as the early RT group, whereas another group of patients who underwent radiotherapy at least 75 days after the beginning of treatment was defined as the late RT group. The response rate (CR + PR) of the early RT group was 92.1% while that of the late RT group was 72.3%. The response rate for radiation therapy thus was significantly better in the early RT group. The 2 and 5-year actuarial survival rates of the early RT group were 22.1% and 9.2%, while those of the late RT group were 19.1% and 8.5%. Then respective median survival times (MST) were 14 months and 13 months. There was no significant difference in survival rates between the two groups. As much as the quality of life is concerned, early RT group would show here better results.

Aged↗
PubMed1996

Association of Helicobacter pylori and diffuse type gastric cancer.

The major purpose of this study was to evaluate the association of Helicobacter pylori and diffuse type gastric cancer (DGC) clinicopathologically (study 1). The second aim was to investigate genetic differences of H. pylori in patients with DGC and intestinal type cancer (IGC) (study 2). The prevalence of H. pylori and the types of histopathological changes were evaluated in resected early gastric cancer (DGC; 25 patients, IGC; 25 patients). Genetic differences of H. pylori in DGC patients (n = 19) and IGC patients (n = 22) were analyzed by polymerase chain reaction (PCR) methods in terms of restriction fragment length polymorphism patterns of the ureB gene and cagA gene positive rates. All patients had evidence of H. pylori infection in the resected stomach, but the positive rate for H. pylori in the area surrounding cancer was 52% (in DGC; 56%, IGC; 48%). But in 40.0% of DGC cases (10/25), mucosal atrophy and intestinal metaplasia were rarely seen in the area surrounding cancer and the positive rate of H. pylori was 80.0% (8/10), in contrast, in 60.0% of IGC cases (15/25), atrophy and metaplasia were progressed and positive rate of H. pylori was 26.7% (4/15) in the area. UreB gene products from 89.5% of DGC cases (17/19) were unable to be digested by Spe I. 31.8% of products from IGC cases (7/22) were also unable to be digested by Spe I, but the positive rate of cagA gene in this group was higher than other groups. The high prevalence of H. pylori infection in DGC patients suggests that H. pylori plays a role in the pathogenesis of DGC, but in the stomach with DGC, it is considered atrophy and intestinal metaplasia are not so implicated in H. pylori, compared with IGC. A genetic specificity of H. pylori in DGC and IGC was indicated by the results, suggesting that H. pylori may play different roles in the pathogenesis of DGC and IGC.

Base Sequence↗
PubMed1996

[Diffuse malignant mesothelioma associated with asbestos pleurisy].

Asbestos pleurisy is relatively uncommon among patients who present with pleural fluid. Association of diffuse malignant mesothelioma with asbestos pleurisy has not been reported in Japan, although 10 cases have been reported in the world literature. We encountered a 51-year-old man in whom diffuse malignant mesothelioma developed during a 5-year course of asbestos pleurisy. Mesothelial cells in patients with asbestos pleurisy are likely to be exposed to asbestos for a long time, which may increase the risk that mesothelioma will develop.

Asbestos↗
PubMed1995

Overexpressed tau protein in cultured cells is phosphorylated without formation of PHF: implication of phosphoprotein phosphatase involvement.

Pyramidal neurons in affected regions of Alzheimer's disease (AD) brain contain neurofibrillary tangles (NFT), aggregates of paired helical filaments (PHF) composed mainly of phosphorylated microtubule-associated protein tau. To explore the role of tau phosphorylation in the aggregation of tau into PHF, we constructed mammalian cell culture systems producing high levels of intracellular phosphorylated tau. COS-1 fibroblast-like cells were transiently transfected to simultaneously express tau, MAP kinase (MAPK), and MAP kinase kinase (MAPKK), or alternatively to express tau and glycogen synthase kinase 3 (GSK3). B103 neuron-like cells (which contain MAPK but little tau or GSK3) were stably transfected to express tau or tau and GSK3. In both systems, GSK3-transfected cells contained tau AT8/M (defined by AT8 staining and tau PHF-like mobility), but MAPK-transfected cells required phosphatase inhibitors, such as okadaic acid (OKA) or calyculin (CAL), to produce tau AT8/M. In vitro, the same concentrations of CAL and OKA inhibit phosphatases 1 and 2A (PP1 and PP2A), except that 100-1000 times as much OKA is needed to inhibit PP1. Inducing tau phosphorylation at the AT8 site in MAPK-transfected cells required 2-10 times more OKA than CAL, suggesting both PP1 and PP2A helped block the phosphorylation. Though levels of tau AT8/M reached 2-8% of total cellular proteins in COS-1 cells, the ratio of particulate to supernatant tau levels did not increase, and no tangles were observed; perhaps post-translational modifications or co-aggregating proteins are needed to induce PHF.

Animals↗
PubMed1995

NACP, the precursor protein of the non-amyloid beta/A4 protein (A beta) component of Alzheimer disease amyloid, binds A beta and stimulates A beta aggregation.

NACP, a 140-amino acid presynaptic protein, is the precursor of NAC [the non-amyloid beta/A4 protein (A beta) component of Alzheimer disease (AD) amyloid], a peptide isolated from and immunologically localized to brain amyloid of patients afflicted with AD. NACP produced in Escherichia coli bound to A beta peptides, the major component of AD amyloid. NACP bound to A beta 1-38 and A beta 25-35 immobilized on nitrocellulose but did not bind to A beta 1-28 on the filter under the same conditions. NACP binding to A beta 1-38 was abolished by addition of A beta 25-35 but not by A beta 1-28, suggesting that the hydrophobic region of the A beta peptide is critical to this binding. NACP-112, a shorter splice variant of NACP containing the NAC sequence, bound to A beta, but NACP delta, a deletion mutant of NACP lacking the NAC domain, did not bind A beta 1-38. Furthermore, binding between NACP-112 and A beta 1-38 was decreased by addition of peptide Y, a peptide that covers the last 15 residues of NAC. In an aqueous solution, A beta 1-38 aggregation was observed when NACP was also present in an incubation mixture at a ratio of 1:125 (NACP/A beta), whereas A beta 1-38 alone or NACP alone did not aggregate under the same conditions, suggesting that the formation of a complex between A beta and NACP may promote aggregation of A beta. Thus, NACP can bind A beta peptides through the specific sequence and can promote A beta aggregation, raising the possibility that NACP may play a role in the development of AD amyloid.

Alzheimer Disease↗
PubMed1995

Structural and functional analysis of the canine histamine H2 receptor by site-directed mutagenesis: N-glycosylation is not vital for its action.

G-protein-coupled receptors generally share a similar structure containing seven membrane-spanning domains and extracellular site(s) for N-glycosylation. The histamine H2 receptor is a member of the family of G-protein-coupled receptors, and has three extracellular potential sites for N-glycosylation (Asn-4, Asn-162 and Asn-168). To date, however, no information has been presented regarding N-glycosylation of the H2 receptor. To investigate the presence, location and functional roles of N-glycosylation of the H2 receptor, site-directed mutagenesis was performed to eliminate the potential site(s) for N-glycosylation singly and collectively. The wild-type and mutated H2 receptors were expressed stably in Chinese hamster ovary (CHO) cells or transiently in COS7 cells. Immunoblotting of the wild-type and mutated H2 receptors with an antiserum directed against the C-terminus of the H2 receptor showed that mutation at Asn-162, but not at Asn-168, resulted in a substantial decrease in the molecular mass. A mutation at Asn-4 led to a further decrease in the molecular mass. Tunicamycin treatment of the transfected cells yielded a sharp band with a molecular mass identical to that of the mutant devoid of all three potential sites for N-glycosylation. These findings indicate that the H2 receptor is N-glycosylated, and that N-glycosylation takes place mainly at two sites, Asn-4 and Asn-162. Neither the affinity for tiotidine nor that for histamine was affected by the mutagenesis. Immunocytochemistry and tiotidine binding showed that the mutated receptors were exclusively distributed on the cell surface in a fashion similar to that of the wild-type. In addition, the glycosylation-defective receptor was capable of activating adenylate cyclase and elevating the intracellular Ca2+ concentration in response to histamine in stable CHO cell lines. Thus N-glycosylation of the H2 receptor is not required for cell surface localization, ligand binding or functional coupling to G-protein(s).

1-Methyl-3-isobutylxanthine↗
PubMed1995

Non-A beta component of Alzheimer's disease amyloid (NAC) is amyloidogenic.

The non-A beta component of Alzheimer's disease (AD) amyloid (NAC) was identified biochemically as the second major component in the amyloid purified from brain tissue of AD patients. NAC, derived from its 140 amino acid long precursor, NACP, is at least 35 amino acids long (NAC35) although its amino terminus is not definitely determined. An antiserum, anti-NAC-X1, was raised against the amino-terminal 9 amino acid sequence of NAC35 and purified on a peptide affinity column. This affinity-purified anti-NAC-X1 antibody immunostained amyloid in AD brain sections and recognized NAC35 but not NACP on Western or dot blot. In aqueous solutions, synthetic NAC35 self-aggregated in a time-, concentration-, and temperature-dependent manner. NAC35 was detected initially as a monomer with a molecular mass of 3500 Da but became aggregated as a function of time into a higher molecular mass component that could not migrate into the gel. The aggregate of NAC35 showed green-gold birefringence after Congo red staining when analyzed under polarized light and fiber-like structure when analyzed ultrastructurally. These results suggest that NAC can form amyloid after it has been cleaved out of its precursor and may be a crucial factor in amyloidosis in the AD brain.

Alzheimer Disease↗
PubMed1995

omega-Hydroxylation of docosahexaenoic acid or arachidonic acid in human colonic well differentiated adenocarcinoma homogenate.

Human colonic well differentiated adenocarcinoma homogenate was incubated with NADPH and docosahexaenoic acid (22:6(n-3)) or arachidonic acid (20:4(n-6)) as a substrate. On a selected ion monitoring chromatogram obtained with reversed phase-high-performance liquid chromatography thermospray mass spectrometry, omega-hydroxydocosahexaenoic acid (omega-HDHE) or omega-hydroxyeicosatetraenoic acid (omega-HETE) from an incubation mixture of the homogenate was detected in significant amount, compared to that from a colonic region remote from the carcinoma. In contrast, epoxydocosapentaenoic acids and the dihydroxy derivatives from 22:6(n-3) or epoxyeicosatrienoic acids and the dihydroxy derivatives from 20:4(n-6) were detected in low amounts, compared to that from a colonic region remote from the carcinoma. The results suggest that highly active NADPH-dependent omega-oxidations of polyunsaturated fatty acids occur in colonic adenocarcinoma homogenate.

Adenocarcinoma↗
PubMed1995

High-performance liquid chromatography-thermospray mass spectrometry of omega-carboxyleukotriene B4 and omega-hydroxyleukotriene B4 from an incubation mixture of human colonic well-differentiated adenocarcinoma homogenate.

A method for the analysis of omega-carboxyleukotriene B4 and omega-hydroxyleukotriene B4 in human colonic carcinoma homogenate is described. The hydroxy groups of the leukotriene metabolite were acetylated by acetic anhydride, and the mixture was partially purified on a Sep-Pak C18 cartridge and analysed by reversed-phase HPLC-thermospray MS. Generally, the base ion, [MH-2(60)]+, is produced through elimination of two acetic acid (60 mass units) molecules from the protonated molecular ion. On selected-ion monitoring, standard curves for omega-carboxy- or omega-hydroxyleukotriene B4 showed a linear relationship over the range 72-1500 pmol. The assay based on selected-ion monitoring was applied to an extract from human colonic carcinoma homogenate. When a homogenate of human colonic well-differentiated adenocarcinoma was incubated with NADPH and leukotriene B4 (60.6 nmol) as a substrate, the conversion of precursor leukotriene B4 to omega-carboxyleukotriene B4 or omega-hydroxyleukotriene B4 was 0.33 or 3.17%, respectively. Based on these results, it is suggested that carcinoma cells themselves or leukocytes at the hostsite in a region of human colonic well-differentiated adenocarcinoma are performing omega-oxidation through NADPH-dependent omega-hydroxylation of leukotriene B4.

Adenocarcinoma↗
PubMed1995

The CYP2D6B mutant allele is overrepresented in the Lewy body variant of Alzheimer's disease.

Approximately one-fourth of neuropathologically confirmed cases of Alzheimer's disease (AD) also have brainstem and neocortical Lewy bodies, constituting a Lewy body variant of AD. Because Lewy bodies are a pathologic hallmark of Parkinson's disease (PD), this subpopulation of AD subjects may have the same risk factors as PD subjects. Analyses of the cytochrome P450 CYP2D6-debrisoquine 4-hydroxylase mutant B allele, a susceptibility gene for PD, revealed a higher representation of this allele in the Lewy body variant of AD than in pure AD or non-AD without Lewy bodies.

Alleles↗
PubMed1995

The CYP2D6B allele is associated with a milder synaptic pathology in Alzheimer's disease.

Both genetic and environmental factors affect the progression of Alzheimer's disease (AD). The presence of cortical Lewy bodies in AD patients is associated with an altered presentation of AD pathology suggestive of an interaction between the pathogenesis of Lewy bodies and AD lesions. Since the CYP2D6B mutant allele is often present in patients with Lewy body diseases (Parkinson's disease and Lewy body variant of AD), we extended these prior observations by studying the neuropathology associated with the presence of the CYP2D6B mutant allele in a pure AD population without Lewy bodies. AD patients who possessed the CYP2D6B mutant allele, in comparison with those without the CYP2D6B allele, were found to have a smaller decline in two synaptic markers, choline acetyltransferase and synaptophysin, in the frontal cortex relative to normal control values. On the other hand, senile plaques and neurofibrillary tangles were not significantly affected by the presence of the CYP2D6B mutant allele in the frontal cortex of AD patients. Association of the CYP2D6B mutant allele with Lewy body formation in both Parkinson's disease and the Lewy body variant of AD and with the milder synaptic pathology in pure AD without Lewy bodies suggest that depending on the contribution of other genetic and environmental factors, this mutant allele may be involved with different aspects of neurodegeneration.

Aged↗
PubMed1995

Genetic evidence that the Lewy body variant is indeed a phenotypic variant of Alzheimer's disease.

Lewy Body Variant (LBV) patients present as Alzheimer's disease (AD) clinically; about two-thirds also have mild extrapyramidal features. At autopsy, neocortical and brain stem Lewy bodies are present in addition to changes diagnostic of AD. We have found that the Apolipoprotein E4 allele is a major genetic risk factor for LBV as it is for "pure AD," in contrast to subjects with diffuse Lewy body disease or Parkinson's disease. This genetic evidence supports the concept that LBV--the second most common neurodegenerative form of dementia--is a phenotypic variant of AD.

Aged↗
PubMed1995

Growth inhibition of human glioma cells modulated by retrovirus gene transfection with antisense IL-8.

The human glioma cell line, NP-1, expresses IL-8 mRNA and constitutively secretes IL-8 protein. Administration of recombinant IL-8 increased the proliferation of NP-1 cells in a dose-dependent manner. In the presence of anti-IL-8 antiserum, the IL-8 mediated proliferation of NP-1 cell growth was inhibited. Further, NP-1 cell growth was inhibited by transfection of retroviral constructs encoding antisense IL-8 both in vitro and in vivo models. These results suggest that antisense IL-8 gene therapy could be beneficial in gliomas where autocrine stimulation by IL-8 is implicated.

3T3 Cells↗