Biomedical subjects

T Saitoh

Publications and source records attributed to T Saitoh.

At least 361 records · Page 20Linked to original sources

PubMed1990

[Assessment of myocardial viability by resting 201Tl SPECT image].

The aim of this study was to assess whether resting 201Tl scintigraphy is superior in detecting viable myocardium than previous conventional methods. We performed not only stress 201Tl SPECT but also resting 201Tl SPECT within one month in 65 patients with coronary artery disease. Resting 201Tl images were quantitatively compared with 4 hour late images of stress study using a polar map. In stress study, redistribution was recognized on 83% (25/30) of non-MI SEGs with perfusion defect in the stress 201Tl image, and on 39% (18/46) of infarcted SEGs. The agreement of resting 201Tl study with 4 hour late images of stress study was shown on 93% (28/30) of non-MI SEGs and on 52% (24/46) of MI SEGs. The increased uptake of 201Tl in resting study, however, was found on 13 (46%) of 28 MI SEGs showing fixed defects in stress study. In stress delayed image with fixed defect, the %Tl uptake of improved SEGs was higher than that of unchanged SEGs (59 +/- 10% vs 48 +/- 11%; p greater than 0.05). There was no viable myocardium which had %Tl uptake less than 40% at stress delayed image. In conclusion, the resting 201Tl imaging will give an important information as for the myocardial viability showing fixed defects, if more than 40% Tl uptake is observed.

Aged↗

PubMed1990

[Estimation of I-123 metaiodobenzylguanidine (MIBG) myocardial washout].

A crosstalk from I-123 to Tl-201 (Tl) window was 35 +/- 30% (mean +/- SD) and 30 +/- 10% in a myocardial phantom and the images of 6 patients respectively. However, the crosstalk from Tl to I-123 was approximately 1% in each. I-123 MIBG (MIBG) and Tl myocardial SPECT images were recorded in 3 normal volunteers (N), 10 patients with myocardial infarction (MI), and 4 with dilated cardiomyopathy (DCM). The MIBG and Tl imagings were performed on the other day to avoid the crosstalk. Myocardial washout rates (WR) of Tl and MIBG were derived from 15 min and 4 hour images. WR of Tl was approximately 36% in each group. On the other hand, WR of MIBG in DCM (52 +/- 7%) and MI (41 +/- 14%) groups were statistically higher than in N (24 +/- 7%) group. Thus WR of MIBG would be useful to detect abnormalities in adrenergic nervous system.

3-Iodobenzylguanidine↗

PubMed1990

[A case of rhabdomyolysis demonstrated by Tc-99m methylene diphosphate scintigraphy].

Technetium-99m phosphate compounds are useful for bone scintigraphy. Furthermore they occasionally demonstrated acute myocardial infarction and myocarditis as positive lesions. Also accumulations in the extraskeletal muscle have been reported using these compounds. This case was a 47-year-old male and had localized rhabdomyolysis, caused by compartment syndrome. We report the usefulness of technetium-99m methylene diphosphonate to diagnose the location of rhabdomyolysis.

Compartment Syndromes↗

PubMed1990

Differential involvement of protein kinase C isozymes in Alzheimer's disease.

Decreased levels of protein kinase C (PKC) and a reduction in the in vitro phosphorylation of a Mr 86,000 protein (P86), the major PKC substrate, are biochemical characteristics of brain tissue from patients with Alzheimer's disease (AD) (Cole et al., 1988). In the current study, we utilized antibodies against individual isozymes of PKC to assess the degree of involvement of different PKC isoforms in AD. The concentration of PKC(beta II) was lower in particulate fractions prepared from AD hippocampal and cortical tissue than in controls and higher in AD cytosol fractions from the cortex than in controls. Immunohistochemical studies in AD neocortex revealed reduced numbers of anti-PKC(beta II)-immunopositive neurons and diminished staining intensity. In contrast, AD hippocampal neurons in CA3-CA4 were more intensely stained with anti-PKC(beta II) antiserum than were controls. The concentration of PKC(beta I) was lower in particulate fractions prepared from AD hippocampus than in controls and was higher in soluble fractions prepared from AD cortex than in controls. The concentration of PKC(alpha) was lower in AD particulate fractions than in controls in the hippocampus. Immunohistochemistry with PKC(alpha) antiserum revealed moderately intense neuron staining and an intense staining of glial cells in AD neocortex. The concentrations and histochemical distributions of PKC(gamma) were not altered in the disease. PKC immunoreactivity was also found in neuritic plaques. The staining patterns of neuritic plaques with different isoform antibodies varied considerably. Anti-PKC(alpha) faintly stained entire plaques and surrounding glial cells; anti-PKC(beta I) stained dystrophic plaque neurites; and anti-PKC(beta II) stained the amyloid-containing portions of plaques.

Aged↗

PubMed1989

Secreted form of amyloid beta protein precursor is involved in the growth regulation of fibroblasts.

Fibroblasts that harbor an antisense construct of amyloid beta protein precursor (ABPP) cDNA, A-1, produced less ABPP mRNA and ABPP and grew poorly. Normal growth was restored when either parent cell conditioned medium (CM) or purified ABPP was provided. The capacity of the CM to restore cell growth was abolished by passage through an anti-ABPP immunoaffinity column; the activity was in the bound fraction. A Mr 90,000 protein recognized by the anti-ABPP antibody was diminished in the CM of A-1. CM from ABPP cDNA-transfected cells expressing high levels of ABPP was more potent than that from non-transfected parent cells in restoring A-1 growth. These results indicate that ABPP is released from cells into the medium and has an autocrine function in growth regulation.

Amyloid↗

PubMed1989

Effect of phospholipase A2 and free fatty acids on lipid-protein interactions in long- and very-long-chain fatty acyl-CoA elongation enzyme systems of brain microsomes.

The elucidation of the mechanism of phospholipase A2-induced inactivation of the condensation enzyme provided evidence concerning the important role of lipid-enzyme interactions in maintaining the condensation activity in swine cerebral microsomes. A quantitative analysis of fatty acid release by phospholipase A2 from the microsomal membrane revealed that only 5 nmol of free fatty acid per mg microsomal protein was released, including oleic acid and arachidonic acid, by treatment with 0.4 unit of phospholipase A2 per mg microsomal protein for 15 s at 23 degrees C. Under these conditions, the condensation activity for endogenous 16:0-CoA and 20:4-CoA decreased to half and that for exogenous 20:0-CoA decreased to 75%. However, the addition of free fatty acids and lysophospholipids or a mixture of them at 5-10 nmol/mg protein did not change the condensation activity for endogenous 16:0-CoA and 20:4-CoA, or for exogenous 20:0-CoA. These results indicated that phospholipase A2 inhibited the condensation activity by acting directly on phospholipids that are indispensable to maintaining the function of the condensation enzyme. The Arrhenius plot for the condensation of endogenous 16:0-CoA showed a break at around 16 degrees C, whereas no break of the plot was observed for the condensation of 20:0-CoA and 20:4-CoA. The activation energy for the condensation of 16:0-CoA and 20:4-CoA was decreased by the addition of free fatty acids such as oleic acid and stearic acid, with disappearance of the Arrhenius break for 16:0-CoA condensation, whereas the activation energy for the condensation of 20:0-CoA was not changed. These results suggest that the type of lipid-protein interaction in the condensation enzyme for 20:0-CoA is different from that for 16:0-CoA and 20:4-CoA.

3-Oxoacyl-(Acyl-Carrier-Protein) Synthase↗

PubMed1989

Amyloid beta protein precursor is a mitogen.

The form of the secreted amyloid beta-protein precursor which contains the protease inhibitor sequence is mitogenic for Swiss 3T3 cells, while the precursor molecule lacking the protease inhibitor domain is not. A ten-fold stimulation of DNA synthesis occurs at 8 x 10(-9) M protein.

Alzheimer Disease↗

PubMed1989

An antiserum against amyloid beta-protein precursor detects a unique peptide in Alzheimer brain.

An antiserum was raised against an amino acid sequence predicted from the DNA sequence of amyloid beta-protein precursor (ABPP), and it was then affinity-purified. This affinity-purified antibody (anti-GID) intensely stained neurons and dystrophic neurites in plaques of Alzheimer's disease (AD) patients, but marginally stained neurons of age-matched normal individuals. Anti-GID antibody detected a series of protein bands with a molecular weight centered at 100,000 and a second band at 55,000 on a blot of the human brain particulate fraction. It also stained a set of bands with a molecular weight around 95,000 and a doublet of Mr 16,000 in the soluble fraction. A band at Mr 35,000 was detected in the soluble fraction prepared from brain tissue of AD patients but not from control brain tissue. A strong immunostaining of AD sections with anti-GID and the presence of a Mr 35,000 band unique to AD might reflect an altered processing of ABPP in AD brains.

Alzheimer Disease↗

PubMed1989

Prophylactic effects of perioperatively administered neocarzinostatin in renal cell carcinoma.

Eighteen patients with stages I to III renal cell carcinoma were treated with Neocarzinostatin before, during and after nephrectomy. The mean cumulative dose of Neocarzinostatin was 18.0 mg. With a minimum follow-up period of 57 months (4.8 years), two of 18 patients developed metastasis and both were dead. Of 17 control patients who were observed for 72 months (6.0 years) or more, ten had recurrent disease and eight of them were dead. The 5-year survival rates were 94% for patients who received Neocarzinostatin and 62% for control patients. There was a statistical difference in survival between these two groups. Neocarzinostatin seems to be effective in the prevention of postoperative recurrence of renal cell carcinoma.

Adult↗

PubMed1989

Phenothiazines reduce ischemic damage to the central nervous system.

We found substantial alterations in reactions catalyzed by calcium/phospholipid-dependent and calcium/calmodulin-dependent protein kinases during CNS ischemia which suggested that phenothiazines, drugs capable of inhibiting these reactions, might reduce neurologic damage. To test this hypothesis, we used chlorpromazine and trifluoperazine. Both drugs reduced neurologic function deficits relative to controls in a rabbit multiple cerebral embolism model and a rabbit spinal cord ischemia model. Chlorpromazine was effective despite reduction of blood pressure, and trifluoperazine did not alter blood pressure. These findings suggest that phenothiazines may be useful for preserving neurologic function when administered shortly after the onset of CNS ischemia.

Animals↗

PubMed1989

Reduced protein kinase C immunoreactivity and altered protein phosphorylation in Alzheimer's disease fibroblasts.

Abnormal protein kinase C levels and protein kinase C-dependent phosphorylation are biochemical alterations in brain tissue obtained from patients with Alzheimer's disease. Because many biochemical and biophysical abnormalities are found in peripheral tissues of patients with Alzheimer's disease, we studied protein kinase C levels and the in vitro phosphorylation of proteins under protein kinase C-activating conditions in fibroblasts derived from patients with Alzheimer's disease. The concentration of protein kinase C-like immunoreactivity was reduced in Alzheimer's disease samples, although the protein kinase C activity determined by the phosphorylation of exogenous histone was not. The degree of in vitro phosphorylation of an Mr 79,000 protein in the presence of protein kinase C activators was less in Alzheimer's disease than in control fibroblast cytosol, and a reduction was more prominent in cases of familial Alzheimer's disease than in sporadic Alzheimer's disease. Therefore, the aberrant phosphorylation mediated by protein kinase C is found not only in the brain but also in fibroblasts.

Alzheimer Disease↗

PubMed1989

Decreased adhesiveness of Alzheimer's disease fibroblasts: is amyloid beta-protein precursor involved?

The adhesiveness of fibroblasts derived from Alzheimer's disease (AD) patients to a plastic substratum was assessed as the proportion of cells attached to a plastic dish bottom after a 30-minute incubation in culture medium of cells dissociated in ethylenediaminetetraacetic acid and was compared with the adhesiveness of normal fibroblasts from non-AD controls. It was found that the normal fibroblasts adhered better to plastic than did AD cells. This reduced adhesiveness was observed in fibroblasts derived from both sporadic and familial AD patients. Because of the possible involvement of amyloid beta-protein precursor (ABPP) in the process of cellular adhesion, the amount of ABPP messenger RNA was measured in these fibroblasts and was found to be decreased in the familial AD fibroblasts, although not in cells from sporadic AD patients. Furthermore, there were fewer molecules detected by an anti-ABPP antibody in conditioned media from familial AD fibroblasts as compared with media from control fibroblasts. Therefore, although it is possible that the reduced adhesiveness of familial AD fibroblasts may result from genetic deficits in ABPP gene expression, the reduced adhesiveness of sporadic AD fibroblasts most likely results from certain deficits in molecules other than the ABPP.

Alzheimer Disease↗

PubMed1989

Ia-expressing microglial cells in experimental allergic encephalomyelitis in rats.

Monoclonal antibodies (MRC OX-6 and OX-17) recognized three types of cells expressing Ia antigen during the course of acute experimental allergic encephalomyelitis (EAE) in rats. In earlier stages of the disease, in animals with or without paralysis, Ia antigens were mostly localized to subarachnoidal and perivascular lymphocytic and histiocytic cell infiltrates, possibly serving as antigen-presenting cells. On the other hand, in convalescent rats, Ia antigens were expressed in a large number of cells with dendritic processes heavily populating the spinal gray matter. The appearance of these Ia-expressing cells in the convalescent stage coincided with the development of degenerating axon terminals in the spinal gray matter. These Ia-expressing cells possessed morphological features characteristic of microglia and were positive for ML-1 lectin but did not express glial fibrillary acidic protein. Immune electron microscopy disclosed the presence of Ia reaction products in the Golgi apparatus, endoplasmic reticulum and plasma membrane of these cells with dendritic processes, indicating active synthesis of Ia molecules in microglia. In addition, Ia antigens were localized to the cells with ultrastructural features of macrophages. Thus, Ia-expressing cells in EAE seems to play dual roles: the induction of immunological reactions during earlier stages and the participation in reparative processes during convalescence.

Animals↗

PubMed1989

Evidence for lysosomal processing of amyloid beta-protein precursor in cultured cells.

Amyloid beta-protein precursor (ABPP) of Alzheimer's disease (AD) represents a family of proteins which includes the parent protein which generates a small (4 kD) fragment that self-assembles to form amyloid fibrils in AD. Thus, the normal and abnormal proteolysis of ABPP may be directly relevant to AD pathogenesis. We have examined the accumulation of ABPP in cultured rodent and human neuronal cell lines in the presence and absence of a battery of protease inhibitors using immunohistochemistry and Western blot analysis. Here we present evidence for a lysosomal pathway for the turnover of ABPP and discuss the relevance of these results to plaque pathology and abnormal ABPP immunostaining in AD.

Amyloid↗

PubMed1989

The regulation of amyloid beta protein precursor secretion and its modulatory role in cell adhesion.

The regulation and function of two forms of the amyloid beta protein precursor (ABPP) that are released into the growth-conditioned medium of the PC12 nerve cell line were examined. Nerve growth factor increases the release of the form of ABPP without the protease-inhibitor domain relative to the protein containing the protease inhibitor and increases the overall rate of ABPP secretion 2-fold. In contrast, fibroblast growth factor increases the rate of ABPP secretion approximately 7-fold. Both forms of the secreted ABPP molecule are, in turn, able to stimulate adhesion of PC12 cells to substrata to which they are adsorbed about 10-fold more efficiently on a molar basis than Iaminin.

Amyloid↗

PubMed1989

Characterization of an amyloid beta precursor protein that binds heparin and contains tyrosine sulfate.

A secreted form of the amyloid beta protein precursor was isolated from the growth conditioned medium of the PC12 sympathetic nerve-like cell line. This protein is recognized by an antiserum that detects a protein of 140 kDa and a less abundant species of 115 kDa on NaDodSO4/acrylamide gels. The amyloid precursor proteins contain O-linked sugars and tyrosine sulfate and bind to the glycosaminoglycan heparin. These results suggest a role for extracellular sulfated glycoproteins in the pathogenesis of Alzheimer disease.

Adrenal Gland Neoplasms↗

PubMed1989

Responsiveness of T cells to mutant major histocompatibility complex class I antigen. II. Role of stimulator-type accessory cells with reference to interleukin 1 production.

Mechanisms of the activation of T cells responding to major histocompatibility complex (MHC) class I antigen were investigated with special reference to interleukin 1 (IL-1) production from stimulator-type accessory cells. For this purpose, we used mainly fractionated Lyt-2+T cells of C57BL/6 (B6) mice as responder cells and irradiated spleen cells or those deprived of adherent cells of B6.C-H-2bm1 (bm1) mice as stimulator cells. Lyt-2+ T cells of B6 mice proliferated in the presence of irradiated whole spleen cells of bm1 mice but did not to Sephadex G-10 column-passed bm1 spleen cells. The unresponsiveness in the latter case was overcome by the supplement of recombinant IL-1 and/or IL-2 in the culture medium. These interleukins were shown to promote the proliferative response of B6 Lyt-2+ T cells in the presence of stimulator-type T or B cells. Both interleukins also facilitated the generation of cytotoxic T cells from B6 Lyt-2+ cells to H-2Kbm1 antigen in the mixed lymphocyte culture deficient in stimulator-type accessory cells. IL-1 was shown to enhance the expression of IL-2 receptor on the responding Lyt-2+ T cells as assessed by flow cytometry. IL-1 binding to responding T cells were also assayed by means of iodinated IL-1 and was shown to increase significantly on responding Lyt-2+ cells. Overall results indicate that accessory cells might play dual roles in the activation of Lyt-2+ T cells responding to allogeneic MHC class I antigen: direct presentation of the antigen to responder T cells and production of IL-1. Both signals are essentially required for Lyt-2+ T cells responding to allogeneic MHC class I antigen to initiate proliferation and also to differentiate into cytotoxic T cells.

Animals↗

PubMed1989

Reduced protein kinase C activity in ischemic spinal cord.

Protein phosphorylation was evaluated in a rabbit spinal cord ischemia model under conditions where cyclic AMP-dependent protein kinase (PK-A) and calcium/phospholipid-dependent protein kinase (PK-C) were activated. One hour of ischemia did not affect PK-A activity significantly; however, PK-C activity was reduced by more than 60%. In vitro phosphorylation of endogenous proteins by endogenous PK-C revealed that eight particulate and five cytosolic proteins showed stimulated phosphorylation by PK-C activators in control tissue, although this stimulation was virtually absent in ischemic samples. When control and ischemic particulate fractions were combined, the endogenous protein phosphorylation pattern under PK-C-activating conditions was similar to the ischemic sample, which suggests that inhibitory molecules may be present in the ischemic particulate fraction. In vitro phosphorylation of endogenous proteins under PK-A-activating conditions in ischemic tissue was similar to that in control tissue. The results suggest that the PK-C phosphorylation system is selectively impaired in ischemic spinal cord. In addition to reduced PK-C-dependent phosphorylation, an Mr 64,000 protein was phosphorylated in ischemic cytosolic samples, but not in control samples. The phosphorylation of the Mr 64,000 protein was neither PK-C-dependent nor PK-A-dependent. These altered phosphorylation reactions may play critical roles in neuronal death during the course of ischemia.

Animals↗