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Biomedical subjects

S Endo

Publications and source records attributed to S Endo.

At least 289 records · Page 16Linked to original sources

In vitro hypoxia of cortical and hippocampal CA1 neurons: glutamate, nitric oxide, and platelet activating factor participate in the mechanism of selective neural death in CA1 neurons.

We prepared neuron-rich cultures from cortical and hippocampal CA1 regions of postnatal day 1 (P1) rats. Using these cultures, we investigated the sensitivity of neurons to hypoxic insults. The effects of MK-801, cycloheximide, NG-nitro-L-arginine (L-NNA), and anti-platelet-activating factor (anti-PAF) IgG on neuronal injury under hypoxic conditions also were examined. The percentage of astroglial cells was higher in CA1 than cortical cultures despite use of the same culture procedure. Despite this finding, the percentage of lactate dehydrogenase (LDH) released into the medium was greater in CA1 than cortical cultures under the conditions of 24-h hypoxia and 24-h incubation (P < 0.05). We then added MK-801 (500 nM), cycloheximide (3 microM), L-NNA (100 microM) and anti-PAF IgG (50 micrograms/ml) prior to inducing the hypoxia and measured LDH in the medium after 24-h hypoxia and 48-h incubation. Under the hypoxic condition, MK-801, L-NNA, and anti-PAF IgG significantly protected the CA1 neurons from hypoxic injury compared with cortical neurons, while cycloheximide protected both cultures equally. These results suggest that CA1 neurons are more sensitive to hypoxia than cerebral cortical neurons, and glutamate, nitric oxide, and PAF may participate in the mechanism of selective neural death in neurons of the CA1 region due to hypoxia.

Animals↗

Diazepam-insensitive GABAA receptors in rat cerebellum and thalamus.

Three major populations of GABAA receptor binding sites are present in cerebellar membranes: diazepam-sensitive [3H]Ro15-4513 binding sites, diazepam-insensitive [3H]Ro15-4513 binding sites and high-affinity [3H]muscimol binding sites. All three populations contain a beta subunit as shown by immunoprecipitation with antibodies that recognize all beta subunits. The beta 3 subtype of beta subunit is contained in all three populations, but only a similar low fraction (< 20%) in each. Thus, the majority contain beta subunits other than beta 3 (beta 2 and beta 1) and beta 3 subunits are not selectively associated with nor lacking in any of the three binding populations. Antibodies to the gamma 2 subunit precipitated similar fractions of [3H]Ro15-4513, [3H]flunitrazepam and [3H]muscimol binding sites, showing that gamma 2 subunits are present in high-affinity muscimol binding isoforms, as well as a significant fraction of the diazepam-insensitive [3H]Ro15-4513 binding sites. Under conditions that identify the 56 kDa alpha 6 subunit on SDS-PAGE as the diazepam insensitive site of [3H]Ro15-4513 binding in cerebellum, no polypeptide showing diazepam-insensitive binding of [3H]Ro15-4513 could be photoaffinity-labeled in rat thalamus. These results suggest that alpha 4 subunits in the thalamus participate primarily in subunit combinations which bind muscimol but not any benzodiazepine site ligands.

Affinity Labels↗

Regulation of cell-cell contacts in developing Drosophila eyes by Dsrc41, a new, close relative of vertebrate c-src.

In Drosophila, Dsrc64 is considered a unique ortholog of the vertebrate c-src; however, we show evidence to the contrary. The closest relative of vertebrate c-src so far found in Drosophila is not Dsrc64, but Dsrc41, a gene identified for the first time here. In contrast to Dsrc64, overexpression of wild-type Dsrc41 caused little or no appreciable phenotypic change in Drosophila. Both gain-of-function and dominant-negative mutations of Dsrc41 caused the formation of supernumerary R7-type neurons, suppressible by one-dose reduction of boss, sev, Ras1, or other genes involved in the Sev pathway. Dominant-negative mutant phenotypes were suppressed and enhanced, respectively, by increasing and decreasing the copy number of wild-type Dsrc41. Colocalization of Dsrc41 protein, actin fibers and DE-cadherin, and Dsrc41-dependent disorganization of actin fibers and putative adherens junctions in precluster cells suggested that Dsrc41 may be involved in the regulation of cytoskeleton organization and cell-cell contacts in developing ommatidia.

Actins↗

Multiple structural elements define the specificity of recombinant human inhibitor-1 as a protein phosphatase-1 inhibitor.

The cDNA encoding human brain protein phosphatase inhibitor-1 (I-1) was expressed in Escherichia coli. Following PKA phosphorylation at a threonine, recombinant human I-1 was indistinguishable from rabbit skeletal muscle I-1 as a potent and specific inhibitor of the type-1 protein serine/threonine phosphatase (PP1). N-Terminal phosphopeptides of I-1 that retained the selectivity of intact human I-1 highlighted a functional domain that mediates PP1 inhibition. Substituting alanine in place of threonine-36 eliminated I-1 phosphorylation by PKA and its phosphatase inhibitor activity. An acidic residue was substituted in place of the phosphoacceptor to produce I-1(T35D), a constitutive phosphate inhibitor. I-1(T35D) was an equally effective inhibitor of PP1 and the type-2 phosphatase, PP2A. However, CNbr digestion of I-1(T35D) yielded an N-terminal peptide that showed 100-fold increased specificity as a PP1 inhibitor. This provided new insight into a unique conformation of the phosphorylated I-1 that accounts for selective inhibition of PP1 activity. Truncation of an active I-1 phosphopeptide identified an N-terminal sequence that was reduced in addition to threonine-35 phosphorylation to inhibit PP1 activity. Biosensor studies demonstrated that PP1 bound to both Phosphorylated and dephosphorylated I-1 and suggested that distinct elements of I-1 structure accounted for PP1 binding and inhibition. Our data point to multiple interactions between the I-1 functional domain. and the PP1 catalytic subunit that define this phosphoprotein as a physiological regulator of the type-1 protein phosphatase.

Amino Acid Sequence↗

The pyramidal cell layer of sector CA 1 shows the lowest hippocampal succinate dehydrogenase activity in normal and postischemic gerbils.

We examined regional differences in the activity of a mitochondrial respiratory enzyme, succinic dehydrogenase (SDH), in the hippocampi of normal and postischemic gerbils, using a quantitative imaging method. Gerbils (n = 21) without ischemia, and gerbils which had experienced 5 min of bilateral common carotid artery occlusion 12 h or 2 days previously, were sacrificed. Coronal sections of the brains were prepared for quantitative imaging of SDH activity and histological examination. In the control gerbils, SDH activity in the pyramidal cell layer of the CA 1 sector (Sommer's sector) was 106.3 +/- 10.3% (mean +/- SD; SDH activity as a percentage of the cerebellar SDH activity), which was lower than in the other subfields of the hippocampus. SDH activity in the oriens layer, stratum radiatum and lacunosum molecular layer of the CA 1 sector was lower than in the corresponding layers of the CA 2 and CA 3 sectors. After transient ischemia, SDH activity remained unchanged in the CA 1 sector. Histologically, selective neuronal necrosis was observed in the pyramidal cell layer of the CA 1 sector 2 days after ischemia. The observed low level of this mitochondrial respiratory enzyme in the pyramidal cell layer of the CA 1 sector should be taken into account as a possible trigger of the selective vulnerability of the region to ischemia.

Animals↗

Chronological changes in the complement system in sepsis.

The time courses of serum complement levels and the severity of sepsis were compared in two groups of septic patients, one in which the patients survived (surviving group) and one in which they did not (nonsurviving group). The components of the complement system, namely, C3a, C4a, C5a, CH50, C3, C4, and C5, were measured at several points in time after the diagnosis of sepsis had been established. A 2-antibody radioimmunoassay was used to measure C3a, C4a, and C5a; the latex agglutination test was used to measure C3 and C4; nephelometry was used to measure C5; and Meyer's 50% hemolysis method was used to measure CH50. Following the diagnosis of sepsis, the levels of CH50, C3, and C4 were significantly lower in the nonsurviving than the surviving group, while the levels of C3a and C4a were significantly higher in the nonsurviving than the surviving group. The C5a levels were significantly higher in the nonsurviving than the surviving group, although no significant intergroup differences were subsequently noted. These results suggest that the serum levels of C3a, C4a, C5a, CH50, C3, and C4 could serve as indices of the severity of sepsis. Thus, monitoring the complement system may be useful for predicting the outcome of patients with sepsis.

Adult↗

Continuous monitoring of short-latency somatosensory evoked potentials during cardiac and aortic surgery.

The effectiveness of monitoring somatosensory evoked potentials (SEPs) intraoperatively to detect brain damage early remains controversial. To assess the diagnostic accuracy of this modality, a study was conducted between 1991 and 1994, recording SEPs in 287 consecutive patients undergoing cardiac and aortic surgery using cardiopulmonary bypass (CPB) with moderate hypothermia or deep hypothermic circulatory arrest. From P1 to N2 of the SEPs occurring within 50 ms latency in response to electrical stimulation of the median nerve were recorded over the contralateral postcentral cortex at 5-min intervals using a Neuropack-2 (Nihon Koden, Tokyo, Japan). Normal SEPs were recovered in 247 patients postoperatively; however, 2 of these patients had suffered a cerebral infarction and 1, a transient stroke intraoperatively, demonstrating a false-negative incidence of 1.2%. On the other hand, three different types of abnormal SEPs were recorded postoperatively. P1 and N1 absence, probably caused by a subcortical lesion, was observed in 4 patients; P2 and N2 absence, probably caused by a cortical lesion, was observed in 8 patients; and a flat SEP, representing diffuse damage, was observed in 2 patients. Among these 14 patients with abnormal SEPs, 7 showed no neurologic disturbance at all, demonstrating a false-positive incidence of 50%. Thus, we concluded that when normal SEPs are recovered during weaning from CPB, the incidence of brain damage could be predicted at below 5%. Conversely, when abnormal SEPs are demonstrated, the incidence of brain dysfunction impeding a return to active life is estimated to be about 70%.

Adolescent↗

Traumatic posterior dislocation of the shoulder with fracture of the acromion in a child.

Posterior dislocation of the shoulder is extremely rare in children. We encountered a posterior dislocation of the shoulder complicated by fracture of the acromion in a 14-year-old boy. He recovered uneventfully after immediate manual reduction performed under general anesthesia and truncal plaster cast fixation. Early diagnosis and treatment are considered to be especially important in managing this injury.

Acromion↗

Acetazolamide produced blood flow velocity changes measured by laser Doppler in gerbils with reduced CBF.

The effect of acetazolamide on the cerebral blood flow was studied in gerbils with unilateral carotid ligation. According to the effect of ligation the animals were divided into three groups: first group-the reduction more than 70%, second-CBF reduction 30-70% and the third group-CBF reduction less than 30%. The effect of acetazolamide administration was closely related to the effect of carotid ligation. More reduction of CBF was produced by carotid ligation, less increase of CBF after acetazolamide injection was noticed. The acetazolamide vascular reserve test was found a sensitive and useful method for detecting even modest reduction of vascular reserve in animals with slight - less than 30% CBF decrease following carotid ligation.

Acetazolamide↗

Flow patterns in dog aortic arch under a steady flow condition simulating mid-systole.

To elucidate the possible connection between blood flow and localized pathogenesis and the development of atherosclerosis in humans, we studied the flow patterns and the distribution of fluid axial velocity and wall shear stress in the aortic arch in detail. This was done by means of flow visualization and high-speed cinemicrographic techniques, using transparent aortic trees prepared from the dog. Under a steady flow condition at inflow Reynolds numbers of 700-1600, which simulated physiologic conditions at early- to mid-systole, slow, spiral secondary, and recirculation flows formed along the left anterior wall of the aortic arch and at the entrance of each side branch adjacent to the vessel wall opposite the flow divider, respectively. The flow in the aortic arch consisted of three major components, namely, an undisturbed parallel flow located close to the common median plane of the arched aorta and its side branches, a clockwise rotational flow formed along the left ventral wall, and the main flow to the side branches, located along the right dorsal wall of the ascending aorta. Thus, looking down the aorta from its origin, the flow in the aortic arch appeared as a single helical flow revolving in a clockwise direction. Regions of low wall shear stress were located along the leading edge of each side branch opposite the flow divider where slow recirculation flows formed, and along the left ventral wall where slow spiral secondary flows formed. If we assume that the flow patterns in the human aortic arch well resemble those observed in the dog, then it is likely that atherosclerotic lesions develop preferentially at these sites of low wall shear stress in the same manner as in human coronary and cerebral arteries.

Animals↗

Acute pathologic features with angiographic correlates of the nearly or completely occluded lesions of the cervical internal carotid artery.

BACKGROUND: The true pathologic process of nearly or completely occluded lesions of the cervical internal carotid artery (ICA) has not been studied sufficiently. This information is important in determining the critical indications for endarterectomy. METHODS: Acute pathologic features of these advanced occlusive lesions of the ICA were studied in 40 patients who underwent emergency carotid endarterectomy. Gross morphologic and histopathologic features of these occlusive lesions were examined, and the relationship between the clinical information and the pathologic characteristics was investigated. RESULTS: Thirty-seven lesions had histologic features of advanced atherosclerosis complicated by fresh intraplaque hemorrhages with or without transintimal extension. Thinwalled neovessels were thought to be an important etiologic factor in producing intraplaque hemorrhage. The remaining three lesions without these changes had strangulated embolic material at the occluded portion. A good correlation between these pathologic features and angiographic findings was found. CONCLUSION: The presented results clearly indicate that intraplaque hemorrhage is the most important factor in producing and determining the acute pathologic features of symptomatic and advanced atheromatous occlusive ICA lesions.

Acute Disease↗

Plasma cytokine levels in patients with severe burn injury--with reference to the relationship between infection and prognosis.

Blood levels of various cytokines were determined in patients with burn injury immediately after the accident, and the relationship between cytokines and morbid condition was investigated. There was almost no marked elevation of cytokines in the early stage of burn injury. Throughout the entire course, tumour necrosis factor alpha, interleukin 6 and interleukin 8, as cytokines, showed high levels in patients with burn injury associated with sepsis and those who died. These levels well reflected the severity in the phase complicated with sepsis.

Accidents↗

Plasma levels of endothelin-1 and thrombomodulin in burn patients.

Plasma concentrations of endothelin-1 (ET-1) and thrombomodulin (TM) were determined in patients with burns to examine their relation to the severity of illness. Tumor necrosis factor-alpha (TNF-alpha) was also measured, and its relationship to ET-1 and TM determined. Twenty-three burn patients were evaluated, who had a total burn surface area (TBSA) of at least 20 per cent. ET-1 was measured by radioimmunoassay (RIA). TM and TNF-alpha were measured by enzyme-linked immunosorbent assay (ELISA). Both the ET-1 and TM concentrations were significantly higher in the patients who developed sepsis than in those who did not and in the patients who eventually died than in those who survived. Maximum plasma concentrations of ET-1 and TM were significantly correlated with the acute physiological and chronic health evaluation II score. There was also a significant correlation between the plasma levels of TNF-alpha and both ET-1 and TM. ET-1 and TM closely reflect the severity of illness in patients with burns in the infectious stage; TNF-alpha may be involved in the production of ET-1 and TM.

APACHE↗

Indications for cisternal irrigation with urokinase in postoperative patients with aneurysmal subarachnoid haemorrhage.

The use of cisternal drainage can lead to complications such as shunt-dependent hydrocephalus and meningitis. We assessed the indications for cisternal irrigation with urokinase in postoperative patients with aneurysmal subarachnoid haemorrhage (SAH). The SAH scores by CT on admission and on the day after surgery were used to evaluate two parameters: the total amount of subarachnoid blood on admission and the clearance rate of subarachnoid blood by surgery. In patients whose parameters values belonged to the range where the total SAH score on admission exceeded 10 points and the surgical clearance rate was less than 50%, the possibility of cerebral infarction was significantly higher in patients without than in those with irrigation (p < 0.05). However, there was no difference between patients with and without irrigation for parameter values outside of the range. Therefore, this range may be useful in providing stricter indications for irrigation therapy with urokinase and thus avoiding the complications of cisternal drainage.

Adult↗