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T Saitoh

Publications and source records attributed to T Saitoh.

At least 343 records · Page 19Linked to original sources
PubMed1990

Protein kinase C is translocated to cell membranes during cerebral ischemia.

The subcellular distribution of PKC(alpha) and PKC(gamma) was studied in homogenates of cerebral cortex from rats subjected to 10 and 15 min of ischemia and 15 min of ischemia followed by 1 h, 6 h, 24 h, 48 h, and 7 days of reperfusion. During ischemia no significant changes in the levels of PKC (alpha) were seen. During the first hour of reperfusion, a transient 2.5-fold (P less than 0.05) increase in PKC (alpha) levels was observed in the particulate fraction. In contrast, a three-fold increase of PKC(gamma) in the particulate fraction concomitant with a 40% decrease in the cytosol was noted during ischemia. In the postischemic phase the levels in the cytosol decreased to 35% of control values at 2 days following ischemia, with a concomitant decrease in the particulate fraction to control levels. The redistribution of PKC to the cell membranes during and following ischemia could be due to ischemia induced receptor activation, increased levels of diacylglycerols, arachidonate and intracellular calcium, and may be of importance for the development of ischemic neuronal damage.

Animals↗
PubMed1990

Increased immunoreactivity of brain spectrin in Alzheimer disease: a marker for synapse loss?

Alzheimer disease (AD) is characterized, among other pathological alterations, by an extensive synapse loss. Brain spectrin is a membrane skeleton protein found in synapses, and its immunoreactivity has been shown to increase in the rat model of denervation. In order to test the hypothesis that there is an increase in brain spectrin immunoreactivity in relation to the synapse pathology in AD, we studied brain sections and homogenates from AD and control cases and found increased anti-brain spectrin immunostaining of neurons, fibers, and plaques, with a relative decrease in the granular pattern of neuropil immunoreactivity. Western blot analysis showed a 25% increase in the 150 kDa bands (degradation products) in the cytosolic fraction and a decrease in the 240 kDa band (intact brain spectrin) in the particulate fraction. Altered immunostaining of brain sections and Western blot was not observed with an antibody against red blood cell spectrin demonstrating the specific change of brain spectrin. These results support the contention that increased brain spectrin immunoreactivity is a marker of synapse or neuronal loss and further supports the concept of synapse pathology in AD.

Alzheimer Disease↗
PubMed1990

A monoclonal antibody Hy20-54-16-3L to lambda (lambda) light chain of human immunoglobulin reacts with amyloid in Alzheimer's disease brain.

We have previously described a monoclonal antibody Hy20-54-16-3L raised against crude primary (AL) amyloid fibrils that preferentially labelled amyloid deposits in the brains of patients with Alzheimer's disease (AD) (Ishii et al., Neuropathol. Appl. Neurobiol., 12 (1986) 441-445). In the present study, we analyzed the protein from an AL-amyloid laden spleen by gel filtration and SDS-PAGE; a partial amino acid sequence of the Hy20-54-16-3L-immunoreactive band excised from Western blots was determined and found to be a lambda light chain of human immunoglobulins. Additionally we have confirmed that this monoclonal antibody reacts with amyloid in AD brain by using a peroxidase-linked immunoelectron microscope technique. It is concluded that an epitope shared with a lambda light chain is included in or associated with amyloid deposits in the AD brain.

Alzheimer Disease↗
PubMed1990

Effect of divalent cations on NADH-dependent and NADPH-dependent cytochrome b5 reduction by hepatic microsomes.

The effect of Ca2+ or Mg2+ on cytochrome b5 reduction by porcine liver microsomes was examined using trypsin-solubilized cytochrome b5 as a substrate. The reduction of exogenous cytochrome b5 by microsomes was low at 1.2 microM cytochrome b5 (3.9 or 2.7 nmol/min/mg protein, respectively, with NADH or NADPH). The addition of CaCl2 greatly enhanced either NADH-dependent or NADPH-dependent cytochrome b5 reduction. At 2 mM CaCl2, the reduction rate was increased to 23- or 18-fold of control, respectively with NADH or NADPH. The concentration for half-maximal effect (EC50) was 0.5 or 0.6 mM in the NADH or NADPH systems, respectively. MgCl2 also stimulated cytochrome b5 reduction with a EC50 value of 1.0 mM in the NADH system or 0.6 mM in the NADPH system. The comparison with the result with KCl indicated that the activation by CaCl2 or MgCl2 is caused mainly by their divalent cation moiety. The Km value for cytochrome b5 was decreased and the Vmax was increased by calcium with either the NADH- or the NADPH-dependent system. NADH-ferricyanide reductase activity was not affected by calcium, but NADPH-ferricyanide reductase activity was stimulated as well as NADPH-cytochrome c reductase activity. In the presence of Triton X-100, divalent cations were inhibitory in NADH-dependent cytochrome b5 reduction, and in contrast, stimulative in NADPH-dependent reaction. These findings suggest that the activation of cytochrome b5 reduction by divalent cations in the NADH system is mainly due to an increasing accessibility of the substrate, and in the NADPH system, in addition to this, a direct effect of divalent cations on NADPH-cytochrome P450 reductase is also involved.

Animals↗
PubMed1990

Stimulated platelets release amyloid beta-protein precursor.

Human platelets can be stimulated by thrombin or ionomycin to secrete soluble truncated amyloid beta-protein precursor and particulate membrane fragments which contain C-terminal and N-terminal immunoreactive amyloid beta-protein precursor. This suggests a possible circulating source of beta-protein in serum which may play a role in the formation of amyloid deposits. The release of soluble amyloid beta-protein precursor could be involved in normal platelet physiology.

Amyloid↗
PubMed1990

Aberrant casein kinase II in Alzheimer's disease.

Abnormal protein phosphorylation has been identified in Alzheimer's disease (AD) for several proteins including a Mr 60,000 protein, a Mr 86,000 protein and a microtubule-associated protein tau. The Mr 86,000 protein is phosphorylated by protein kinase C, whereas protein kinases responsible for other aberrant phosphorylation reactions are not known. In addition to protein kinase C, another kinase, casein kinase II (CK-II), has now been shown to be aberrant in AD. The spermine-dependent CK-II activity is reduced by 84% in AD and the amount of CK-II as determined by its immunoreactivity on a Western blot is reduced by 63%. Furthermore, the distribution of CK-II in AD is altered. Although the neuronal cell body reacts well with CK-II antisera in the normal cortex, the non-tangle-bearing neurons in the AD cortex showed a 15-30% decrease in anti-CK-II immunoreactivity. The neurofibrillary tangles, on the other hand, stain very strongly with rabbit anti-CK-II and indicates that CK-II may be involved in the pathology of AD. The study of CK-II immunoreactivity for dementing diseases other than AD revealed a similar reduction, suggesting the CK-II involvement in the common process of neurodegeneration.

Aged↗
PubMed1990

Changes in signal transduction in Alzheimer's disease.

We studied the signal transduction system including the receptor and protein kinase C (PKC) in Alzheimer's disease (AD) brains. We used 3H-TCP as a ligand for the NMDA receptor-ion channel complex. The total concentrations of 3H-TCP binding sites were significantly reduced in AD frontal cortex. 3H-TCP binding sites spared in AD brains retained the affinity for the ligand and the reactivity to NMDA, L-glutamate, and glycine. We utilized antibodies to assess the degree of involvement of different PKC isoforms in AD. The concentration of PKC (beta II) was lower in AD particulate fractions and higher in AD cytosol fractions. Immunocytochemical studies revealed reduced numbers of anti-PKC (beta II)-immunopositive neurons. Anti-PKC (alpha) faintly stained entire plaques and surrounding glial cells. Anti-PKC (beta I) stained dystrophic plaque neurites. Anti-PKC (beta II) stained the amyloid-containing portions of plaques. These results suggest an involvement of second messenger cascades in the pathogenesis of AD in addition to neurotransmitters and their receptors.

Aged↗
PubMed1990

Ductal lesions of exocrine glands and insulitis induced by L3T4+ T cells following graft-versus-host reaction due to major histocompatibility complex class II disparity.

Recently, we have demonstrated characteristic hepatic lesions resembling primary biliary cirrhosis (PBC) in semiallogeneic F1 hybrid mice with major histocompatibility complex (MHC) class II-disparate graft-versus-host reaction (GVHR). In the present study, we tried to reveal other ductal lesions in extrahepatic organs, including salivary glands and pancreas. Murine strains used are C57BL/6 (B6), B6 mutant bm1, and bm12. bm1 carries a mutant gene at the H-2K locus of MHC and bm12 carries a mutant gene at the I-A locus of MHC of the B6 strain. The (B6 x bm1)F1, (B6 x bm12)F1, and (bm1 x bm12)F1 mice were injected intravenously with 1 x 10(7) B6 L3T4+ or Lyt-2+ T cells and were sacrificed on the 14th day postinjection for histological examinations. Mononuclear cell infiltration was detected around the ducts of salivary glands only in (B6 x bm12)F1 mice injected with B6 L3T4+ T cells. A moderate to marked level of cell infiltration was demonstrated in pancreas of (B6 x bm12)F1 recipients similar to nonobese diabetic (NOD) mice. By immunohistochemical examinations, infiltrating cells were shown to consist not only of L3T4+ but also of Lyt-2+ T cells, even after the inoculation of L3T4+ cells. These results are discussed in reference to mechanisms of organ-specific autoimmune diseases, especially insulitis in NOD mice which show insulin-dependent diabetes mellitus.

Animals↗
PubMed1990

[Studies on the giardiasis as the zoonosis].

To obtain basic data on the route of Giardia infection as zoonosis, we examined feces from 80 dogs and 16 cats for Giardia cysts and evaluated the detection rates. In addition, familial infection was studied in 3 family members of the patient with giardiasis. Giardia cysts were detected in 10 of the 80 dogs (12.5%) but none of the cats. Of the 10 dogs from which Giardia cysts were isolated, 6 had been maintained by the breeders. Tow other dogs were for examination in the research institutions. None of the family members of the patient with giardiasis had this infection. Since the detection rates of Giardia cysts in the dogs and cats were low, the possibility that human infection is acquired from dogs or cats seemed to be low. However, some of patients with giardiasis we encountered had never been abroad. This fact together with the presence of Giardia cysts in the dogs despite the low detection rates suggest that attention should be paid to the possible association between human giardiasis and pets since the number of people keeping pets is increasing.

Animals↗
PubMed1990

Hyper-response of insulin release to arginine in streptozotocin-induced diabetic rats with hepatic vagotomy.

Vagal glucose receptor and arginine sensor have been found to exist in the liver of normal rats. The present study was designed to examine whether these sensory receptor systems function in streptozotocin-induced mildly diabetic rats. One week after streptozotocin injection (35 mg/kg body wt. iv), hepatic vagotomy and installation of a jugular vein catheter were performed. Three days after the surgery, intraperitoneal glucose (1 g/kg body wt.) or arginine (1 g/kg body wt.) stimulation was done with the rat in an unanesthetized and unrestrained state. Hepatic vagotomy significantly reduced glucose-induced insulin release with an increase in plasma glucose in control and diabetic rats. The rate of reduction of plasma insulin release was similar in the two groups. Hepatic vagotomy also significantly enhanced arginine-induced insulin release in both groups, but in control rats there was no change in the response to plasma glucose, while in diabetic rats there was a significant reduction. The rate of enhancement of plasma insulin release by hepatic vagotomy was significantly greater in diabetic than in control rats. The results indicate that streptozotocin-induced mildly diabetic rats have hyperfunction of the arginine sensor and normofunction of the glucose receptor and modulate insulin release through these receptor systems in the liver.

Animals↗
PubMed1990

Successful removal of an angiographically occult arteriovenous malformation of the ventral medulla.

A case with an angiographically occult arteriovenous malformation (AVM) of the ventral medulla presenting with progressive motor and sensory deficits is reported. The AVM, about 1 x 1 x 0.5 cm in size, accompanied by intramedullary haematoma, was successfully removed through a small incision placed in the right ventrolateral medulla between the vagus and the hypoglossal nerves. The patient's neurological symptoms improved after surgery.

Cerebral Hemorrhage↗
PubMed1990

Increased maternal plasma concentration of endothelin-1 during labor pain or on delivery and the existence of a large amount of endothelin-1 in amniotic fluid.

The concentration of endothelin-1 (ET-1) in plasma and amniotic fluid from normal pregnant women was determined by a sensitive sandwich-enzyme immunoassay system, established recently. The plasma ET-1 level increased gradually during normal pregnancy as the pregnancy advanced, the levels (0.40 +/- 0.02 pmol/l, n = 45) being significantly (p less than 0.05) higher after 29 weeks of gestation than those (0.32 +/- 0.01 pmol/l, n = 30) before 28 weeks of gestation. The plasma ET-1 level during labor pain was significantly higher (0.59 +/- 0.06 pmol/l, n = 10) than that (0.40 +/- 0.02 pmol/l, n = 45) in the 3rd trimester of pregnancy without labor pain (p less than 0.02). Moreover, a high level of ET-1 (17.38 +/- 0.25 pmol/l, n = 18) was detected in amniotic fluid on term delivery. The ET-1 level in amniotic fluid was significantly higher than the levels in maternal and umbilical cord plasma (p less than 0.001 and p less than 0.001, respectively). After delivery the maternal ET-1 level decreased gradually and 2 day postpartum ET-1 levels reached the normal non-pregnant level.

Adult↗
PubMed1990

[Estimation of glomerular filtration rate from the urinary excreted contrast medium concentration].

In the animal experiments, glomerular filtration rate (GFR) values were estimated from the urinary response to the intravenously administrated iopamidol. By introducing some reasonable assumptions, mass balance equations about the contrast medium were transformed and GFR was defined as the ratio of logarithm of urinary concentration by time. Urinary concentrations were determined by measuring the photodensity on the X-ray film of urine specimens. Obtained values of GFR were well fitted to those obtained by the analysis of the plasma disappearance curve. The advantage of this method is that measurement of urinary volume is not necessary.

Animals↗
PubMed1990

Alz-50 recognizes a phosphorylated epitope of tau protein.

Alz-50 is a monoclonal antibody that detects antigens enriched in the brain tissue of Alzheimer's disease (AD) patients. Although Alz-50 recognizes tau, an identified integral constituent of the AD paired helical filament (PHF), the exact nature of the antigenic site is unknown. An immunoblot analysis demonstrated that the antigenic sites to Alz-50 are diminished by acid phosphatase treatment. Consistent with this finding, Alz-50 antigens were more concentrated in brain homogenates prepared with phosphatase inhibitors. The epitope in tau with which Alz-50 reacts is located in the carboxy terminus within a 14-amino acid region from just beyond the microtubule-binding repeats to the carboxy terminus. An isolated carboxy-terminal chymotryptic peptide from bovine brain tau reactive with Alz-50 was analyzed by fast-atom-bombardment mass spectroscopy (FAB-MS) and was found to be present as both a monophosphopeptide and a nonphosphorylated peptide. The immunohistological analysis has demonstrated that Alz-50 staining of neurofibrillary tangles (NFTs) is sensitive to acid phosphatase but not to alkaline phosphatase. Furthermore, Alz-50 staining of NFTs was effectively adsorbed by a high concentration of phosphoserine but not by serine or phosphothreonine. These results strongly suggest that Alz-50 recognizes a phosphorylated epitope in the carboxy terminus of tau which has not been previously detected by using alkaline phosphatase. The strong Alz-50 staining in AD samples may represent another association between a phosphorylation state and neurofibrillary lesions. As a marker of the inchoate tangle-bearing neuron, the characterization of the Alz-50 epitope in tau offers a partial molecular basis for the modifications that contribute to the assembly of PHFs.

Acid Phosphatase↗
PubMed1990

Protein phosphorylation during ischemia.

Many investigations have shown that calcium and adenosine triphosphate are crucial to central nervous system functions. It is probable that alterations of these substances during central nervous system ischemia are involved in the processes that cause irreversible neural damage. Calcium regulates several protein kinases that are responsible for phosphorylation of proteins vital for many central nervous system functions. Using a rabbit spinal cord ischemia model, we found protein kinase C and calcium/calmodulin-dependent kinase were severely affected during the first hour of ischemia. Protein kinase A was not significantly affected. The time course of lost protein kinase C enzyme activity closely corresponded to irreversible loss of neurologic function, and there is evidence that protein kinase C inhibitor activity is generated. Also, drugs that inhibit protein kinase C increased neurologic damage when administered during the early phases of ischemia. These results suggest that protein phosphorylation, particularly by protein kinase C, is critical to maintenance of neurologic function.

Animals↗
PubMed1990

[Recovery from cardiac arrest by prostaglandin E1 infusion during emergency open heart surgery].

A 21 day old infant, diagnosed as ASD, VSD, and PDA, was scheduled for an emergency radical operation. After admission, she fell into cardiac failure and was treated with artificial ventilation and infusion of inotropic agents. Anesthesia was induced with fentanyl and maintained with continuous fentanyl infusion and chlorpromazine. Dopamine and dobutamine were administered before she underwent a cor-pulmonary by-pass. At the time of release of aortic clamping, her blood pressure went down and dopamine, dobutamine and isoproterenol were administered. After completion of the cor-pulmonary by-pass, tachy-arrhythmia and hypotension occurred. Digitalis and calcium did not reverse the condition. The thorax was reopened and BP rose. After 15 min, ventricular fibrillation occurred. Defibrillation was carried out, but the heart was arrested. Even with pacing and cardiac massage, cardiac contraction did not resume. However immediately on intravenous administration of PGE1, 40 ng.kg-1.min-1, the heart started to beat. The cause of recovery from cardiac arrest was speculated to be due to reuptake of intracellular Ca2+ by PGE1. We stress therefore, that during and after cor-pulmonary by-pass procedures, PGE1 infusion may be beneficial.

Alprostadil↗