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T Saitoh

Publications and source records attributed to T Saitoh.

At least 271 records · Page 15Linked to original sources
PubMed1993

Relation between glucose-stimulated insulin secretion and intracellular calcium accumulation studied with a superfusion system of a glucose-responsive pancreatic beta-cell line MIN6.

The concept that cytosolic free calcium is the primary signal for insulin secretion is generally accepted, but studies with intact pancreatic beta-cells of the cytosolic free calcium concentration-insulin secretion relationship have produced contradictory and sometimes confusing data. We designed a superfusion system of a pancreatic beta-cell line, MIN6, loaded with fura-2, which allowed simultaneous measurement of cytosolic free calcium concentration and insulin secretion. MIN6 cells released insulin in response to high glucose, thus resembling events in normal islet cells. Cytosolic free calcium concentration and insulin secretion rapidly increased, and the increase was suppressed by mannoheptulose or by sodium azide. This increase was suppressed by lowering the temperature of the medium. Cytosolic free calcium concentration and the insulin secretion induced by leucine were not influenced by mannoheptulose but were inhibited by sodium azide. In RINm5F cells, cytosolic free calcium concentration and insulin release were slightly suppressed by glucose but were increased by ionomycin. There was a close relation between the rise in cytosolic free calcium concentration and insulin secretion in all cases. Our findings provide a direct evidence that a rise in cytosolic free calcium concentration depends on glucose metabolism and is a primary signal for insulin secretion.

Animals↗
PubMed1993

[Estimation of effective half life of 131I in radioiodine therapy for Graves' disease using a single radioiodine uptake measurement].

Calculation of the absorbed radioiodine dose in the thyroid gland is a very important factor in 131I therapy for Graves' disease. In 131I therapy, the measurement of the effective half life (EHL) of radioiodine in the thyroid gland is indispensable for calculating the absorbed radioiodine dose. In some cases, however, EHL cannot be calculated because repeated measurements of thyroid uptake cannot be done. So, the authors developed a new method to estimate EHL using a single radioiodine uptake measurement. The activity of intrathyroidal 131I (thyroid uptake) and that of the surrounding area of the shielded thyroid (body background) were measured at 24 hours after the administration of 131I. The ratio of the value of body background to thyroid uptake was calculated. This ratio was multiplied by 100 and the calculated value was named the EHL-index. The relationship between actual measured EHL and the EHL-index was expressed by a regression line and/or a hyperbola. For the purpose of obtaining more actual values of EHL using the EHL-index, the new combined curve was composed of the regression line and the hyperbola. As for the value of calculated EHL compared with that of actual measured EHL, about 80 percent of calculated EHL values were within acceptable error ranges. These results indicate that EHL can be estimated by a single measurement 24 hours after administration of 131I. This method should be very useful in the therapy of Graves' disease with 131I when the thyroid measurement is performed only one time.

Graves Disease↗
PubMed1993

Immunoreactivity of the nuclear antigen p105 is associated with plaques and tangles in Alzheimer's disease.

BACKGROUND: The protein p105 is a nuclear antigen associated with cell proliferation. Recent investigations have indicated that many molecules previously considered to be growth-associated are actually involved in plasticity of the central nervous system. EXPERIMENTAL DESIGN: For the present study, using immunohistochemical and immunochemical techniques in control and Alzheimer's disease (AD) brain, we explored the possibility that p105 could be involved in the aberrant sprouting response. AD tissue was used because in this disorder, the neuronal sprouting processes display a disruption in their cytoskeleton and the microtubule-associated protein, tau is abnormally phosphorylated. Control experiments were performed with the p105 antibody from an independent source, and with an antibody against Ki-67. RESULTS: The antibody against p105 (but not against Ki-67) immunolabeled the tangles, neuropil threads, and a subpopulation of fusiform neurites in the plaque. The p105 immunoreactivity was colocalized with tau and the numbers of tangles immunostained with p105 antibody correlated with the number of tangles immunolabeled with an antibody against tau. Western blot analysis of human brain homogenates showed that the antibody against p105 immunostained a major band at an estimated molecular weight of 105 kilodaltons and a secondary band at 84 kilodaltons. In AD frontal cortex, there was a significant increase in the 84 kilodalton band in the particulate, but not in the cytosolic fraction. CONCLUSIONS: The characterization of the patterns of expression of this class of nuclear antigen in the brain might provide important clues as to the mechanisms of plasticity and abnormal growth under normal conditions, as well as in AD.

Aged↗
PubMed1993

[Clinico-pathological study of Helicobacter pylori in early gastric cancer].

The role of Helicobacter pylori (Hp) infection in the pathogenesis of various gastric diseases is an important but unresolved issue. To investigate the association between Hp and the histological findings of the stomach in patients of early gastric cancer, the prevalence of Hp in gastric mucosa and the mucosal alterations were examined histo-pathologically in the surgically resected stomach of 30 cases with early gastric cancer. Serum IgG antibodies for Hp were determined in these cases. All 30 cases had evidence of Hp infection in resected stomach and 90% had Hp antibodies in their serum. There was no evidence of direct association between Hp and gastric cancer histopathologically, although it is considered that chronic gastritis (atrophy and intestinal metaplasia) are implicated in Hp infection.

Adenocarcinoma↗
PubMed1993

[Experimental study on intraoperative irradiation for pancreatic cancer: histological and nutritional changes in early phase after high dose irradiation].

For the treatment of pancreatic head cancer, pancreatoduodenectomy is followed by the intraoperative radiation therapy (IORT). The present dose adopted ranged 20 to 30 Gy, however the dose is believed to be insufficient for local control of adenocarcinoma cells. In this study, high dose IORT was performed using rabbit, so histological and nutritional changes were evaluated. Rabbits were divided in three groups; 30 Gy, 50 Gy, 80 Gy. The radiation was performed with electrons focusing base of cranial mesenteric artery (SMA in human). The rabbits were sacrificed at intervals ranging from immediately after to 4 weeks following irradiation. The earliest evidence of histological changes was the loss of endothel, although it was repaired within 1 week. Fragmentation and reduplication of internal elastic lamina were observed after 1 week, however the degree was not dose dependent. Damages of the media was observed in 50 and 80 Gy groups. That is, focal degeneration of smooth muscle cell was demonstrated in 50 Gy group and medial necrosis in 80 Gy group. Degeneration of ganglion cells was observed and its severity was dose dependent. In 80 Gy group, diarrhea occurred more frequently compared with the other groups and body weight loss couldn't recover within 4 weeks. It is concluded that, since necrosis of aortic media and marked degeneration of ganglion cells are inevitable in 80 Gy group, IORT dose should be increased within 50 Gy.

Animals↗
PubMed1993

[Left ventricular function during hypoxia--II: Effects of intramyocardial pH].

We investigated the effects of intramyocardial acidosis on cardiac function during hypoxia in mongrel dogs (n = 50). Intramyocardial pH in subendocardium of left ventricle was measured continuously using a pH electrode. During hypoxia (PaO2 = 20 mmHg) caused by inhalation of low oxygen fraction, intramyocardial pH decreased significantly following initial enhancement. Intramyocardial pH correlated significantly with arterial pH, base excess, lactic acid (LA) levels, coronary venous PcO2, and coronary venous-arterial PcO2 difference. There were significant correlations between intramyocardial pH with maximum rate of rise of left ventricular pressure (LV dp/dt max), left ventricular end-diastolic pressure (LVEDP), LVEDP/LVP and the time constant of exponential isovolumic left ventricular pressure fall. High arterial LA levels tended to cease myocardial LA uptake and production, turning LA balance into zero. LV dp/dt max was low in such a condition. Myocardial LA production decreased intramyocardial pH, but LV dp/dt max was maintained at high levels of LA production. These observations suggest that myocardial LA production maintains left ventricular function with the increase of ATP by acceleration of anaerobic glycolysis. In conclusion, during hypoxia, intramyocardial acidosis was caused by the increase of arterial LA level, myocardial anaerobic glycolysis and ATP breakdown, and it worsened left ventricular contractile function and relaxation. Arterial LA levels can play a major part in intramyocardial acidosis, but the increase in myocardial LA production might be beneficial to left ventricular contractile function.

Animals↗
PubMed1993

[Pseudo-false aneurysm of the left ventricle perforated into the right ventricle--a case report].

A case of pseudo-false aneurysm of the left ventricle perforated into the right ventricle was reported. The patient was 60-year-old male with acute inferior myocardial infarction. Echocardiography showed a thin wall cavity on the apex of the right ventricle. Communication between the left ventricle and the right ventricle was detected on pulsed Doppler echocardiography. Surgery revealed a pseudo-false aneurysm in the free wall of the right ventricle communicating to both ventricles. We emphasize the importance of preoperative morphological and hemodynamic evaluation with Doppler echocardiography in the case of post-myocardial infarction ventricular septal perforation.

Heart Aneurysm↗
PubMed1993

[Left ventricular function during hypoxia. 1: Effect of blood glucose level].

We investigated the effects of blood glucose levels and myocardial glucose uptake on cardiac function during hypoxia in mongrel dogs (N = 50). During hypoxia (PaO2 = 20 mmHg) caused by inhalation of low concentration of oxygen for 2 hours, left ventricular (LV) function including LV pressure, maximum rate of rise of LV pressure, and cardiac index decreased significantly following initial enhancement. There were significant correlations between these hemodynamic parameters and blood glucose levels. The blood glucose levels correlated significantly with myocardial glucose uptake and blood lactic acid levels (r = 0.660: P = 0.000, r = 0.380: P = 0.000, respectively). Eight of nine dogs which died within 90 minutes during hypoxia showed low blood glucose levels and high lactic acid levels. During hypoxia, myocardial glucose uptake increased to more than five times of control value. On the other hand myocardial lactic acid uptake decreased and turned to production. At the same degree of blood lactic acid levels, LV function was maintained better with high blood glucose levels than with low levels. With low blood glucose levels, myocardial lactic acid uptake and production tended to cease. The pronounced change in LV function during hypoxia could be partially explained by decreased production of ATP due to decrease in myocardial glucose uptake and high lactic acid levels. It seems that high blood glucose levels are preferable to maintain cardiac performance under such a condition.

Animals↗
PubMed1992

An endosomal-lysosomal pathway for degradation of amyloid precursor protein.

We previously reported evidence for a lysosomal degradative pathway for APP and C-terminal fragments thereof, based on Western and immunocytochemical analysis of drug-treated cells. Here, we verify the existence of a lysosomal degradative pathway for APP using pulse chase immunoprecipitation analysis of drug-treated cells and fibroblasts with and without a known lysosomal hydrolase targeting defect. The results are consistent with the hypothesis that part or all of the beta-protein domain of APP is normally degraded by lysosomes. A mechanism for beta-protein deposition based on this data is hypothesized.

Amyloid beta-Protein Precursor↗
PubMed1992

Amyloid precursor protein is localized in growing neurites of neonatal rat brain.

Previous studies have indicated that amyloid precursor protein (APP) might be a trophic agent in the nervous system, possibly through the regulation of cell adhesion and the protease/protease inhibitor activity. Additionally, APP is upregulated during the development of the nervous system. In order to further study the role of APP in neuritic outgrowth, we examined the patterns of distribution of APP in the immature neonatal rat brain (P1). Laser-scanning confocal imaging of double-immunolabeled sections showed that a subpopulation of the anti-GAP43-immunoreactive outgrowing neurites contained APP immunoreactivity in the neocortex and hippocampus. These fine, long neuritic processes were also positive with antibodies against phosphorylated neurofilaments and were glial fibrillary acidic protein (GFAP) negative. In addition, anti-APP strongly immunolabeled neurons in the inner cortical layers, while GAP43 strongly immunolabeled the neuropil surrounding them. These observations are consistent with a previous study where APP was localized to aberrant sprouting neurites and suggest a possible role for APP in neuritic outgrowth in plaques of patients with Alzheimer's disease (AD), which might explain the abnormal neuritic response found in AD.

Amyloid beta-Protein Precursor↗
PubMed1992

The involvement of protein kinase C in activation-induced cell death in T-cell hybridoma.

T-cell hybridoma activated by a variety of stimuli such as anti-cell surface antigen, notably CD3 and T-cell receptors, and Con A undergoes a cell lysis process called activation-induced cell death (AICD). It was found that the major protein kinase C (PKC) isoform in the 2B4.11 T-cell hybridoma, PKC(alpha), was translocated from the cytosolic to the particulate fraction when these hybridoma cells were induced to die by plastic-adsorbed anti-CD3 antibodies. Inhibitors of protein phosphorylation rescued 2B4.11 cells from AICD as determined by the analysis of cellular metabolism and the proportion of living cells. Furthermore, PKC(alpha) down-regulation by phorbol ester treatment abolished AICD, and the degree of PKC down-regulation correlated well with the degree of AICD abolishment, suggesting that PKC activation represents an essential step in the molecular mechanisms underlying AICD in this T-cell hybridoma.

Alkaloids↗
PubMed1992

Localization of amyloid precursor protein in GAP43-immunoreactive aberrant sprouting neurites in Alzheimer's disease.

Previous in vitro studies have suggested that amyloid precursor protein (APP) could be involved in cell surface adhesion, neuritic growth and survival of hippocampal neurons. In the present study, involvement of APP in aberrant sprouting in Alzheimer's disease (AD) was studied by comparing immunolabeling patterns of anti-APP and anti-growth-associated protein 43 (anti-GAP43). Confocal laser imaging of frontal cortex sections double-immunolabeled for APP and GAP43 showed an increase, in AD, of presynaptic boutons immunostained with anti-GAP43 that contained anti-APP immunoreactivity. The neuritic plaques in AD cases presented intense anti-GAP43 immunoreactive abnormal neurites colocalized with anti-APP. Three-dimensional reconstruction of the plaques showed that anti-APP was colocalized with anti-GAP43 in 57.5% of the aberrant sprouting neurites. We conclude that co-expression of APP with GAP43 in the plaque might be involved in the aberrant sprouting response observed in AD.

Aged↗
PubMed1992

Casein kinase II is associated with neurofibrillary tangles but is not an intrinsic component of paired helical filaments.

Neurofibrillary tangles (NFT) are pathological cytoskeletal structures composed of paired helical filaments (PHF), and are found in neurons of patients afflicted with many neurodegenerative disorders, including Alzheimer's disease (AD). We previously found that an antiserum against casein kinase II (CK-II) stained NFT intensely in the brain tissue of AD patients. In the current study, we found that the anti-CK-II antiserum stains NFT and neuronal inclusions in many other neurodegenerative diseases as well, including Guam-Parkinson dementia complex, chromosome 18 deletion syndrome, progressive supranuclear palsy, Kufs' disease, and Pick's disease. This antiserum reacted, in crude brain homogenates, with both a doublet of Mr 43,000 and a Mr 27,000 Da protein which could correspond to the alpha, alpha', and beta chains of CK-II. The staining of these bands was adsorbed by preincubating anti-CK-II antiserum with purified CK-II. Preincubation of brain sections with purified CK-II strongly intensified the immunostaining of NFT with anti-CK-II, suggesting that NFT may bind CK-II. In the AD brain homogenates, the particulate CK-II levels are increased whereas the cytosolic levels are decreased without a change in total CK-II levels, consistent with the idea that CK-II binds to the particulate PHF, a major constituent of NFT. In accord with these findings, purified PHF bound CK-II, but purified PHF did not contain CK-II as its component. These results suggest that CK-II might be an extraneously deposited component of NFT. Thus, the altered CK-II compartmentalization might have significant consequences in the pathogenesis of AD.

Brain↗
PubMed1992

Bacterial expression, purification, and functional mapping of the amyloid beta/A4 protein precursor.

The secreted form of Alzheimer amyloid beta/A4 protein precursor (APP) has been shown to be involved in cell growth regulation (Saitoh, T., Sundsmo, M., Roch, J.-M., Kimura, N., Cole, G., Schubert, D., Oltersdorf, T., and Schenk, D.B. (1989) Cell 58, 615-622). Using a strong prokaryotic expression system, we expressed, in Escherichia coli, peptide fragments covering different regions of the secreted form of APP-695. The longest of these fragments (KB75, 572 amino acids from Val-20 to Ile-591), which contained neither the Kunitz-type protease inhibitor (KPI) domain nor the amyloid beta/A4-protein domain, was purified and shown to be biologically active in terms of growth regulation. Two other APP fragments (KB48, 316 amino acids from Val-20 to Met-335; and RB17, 150 amino acids from Thr-296 to Pro-445), overlapping by only 40 amino acids at a close site C-terminal to the KPI insertion site, were also active. Furthermore, a chemically synthesized 40-residue peptide corresponding to this region of overlap also stimulated the growth of A-1 fibroblasts. These results establish the presence of growth-promoting activity in the secreted form of APP-695 and suggest that the site of this activity of APP-695 lies within a 40-amino acid domain next to the KPI insertion site.

Amino Acid Sequence↗
PubMed1992

Serological alpha 1-antichymotrypsin in Down's syndrome and Alzheimer's disease.

alpha 1-Antichymotrypsin (ACT) is a serine protease inhibitor that is markedly elevated in the serum and cerebrospinal fluid of patients with Alzheimer's disease (AD). Patients with Down's syndrome are known to develop neuropathological changes of AD by age 40 years and many become demented. Therefore, in the present study, we obtained serum ACT levels from patients with Down's syndrome and AD, diagnosed by autopsy or clinically, and healthy control subjects. Newman-Keuls' multiple range test revealed a significantly greater (p less than 0.01) mean ACT level in the Autopsy AD (906.4 +/- 94.64 mg/L) and Clinical AD (745.00 +/- 59.95 mg/L) groups in contrast to the Old Control group (531.00 +/- 23.05 mg/L). The mean ACT level of the Down's Syndrome group (513.33 +/- 14.73 mg/L) was not significantly different from that of the Young Control subjects. Furthermore, we did not observe a positive correlation of ACT levels with age in the Down's Syndrome group, in spite of the age-dependent premature increase in neuropathological changes of AD that are known to occur in patients with Down's syndrome. A positive correlation between serum ACT levels and the density of plaques or tangles, neuropathological hallmarks of AD, in brains of patients with AD also did not exist. Thus, our results suggest that ACT levels may not parallel the development of the classical neuropathological hallmarks of AD.

Adult↗