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Biomedical subjects

T Sakamoto

Publications and source records attributed to T Sakamoto.

At least 1,423 records · Page 79Linked to original sources
PubMedDate not supplied

Interferon beta affects retinal pigment epithelial cell proliferation via protein kinase C pathways.

BACKGROUND: The aim of this study is to see the effect of interferon beta (IFN-beta) on cell proliferation and the protein kinase C (PKC) signaling pathway. METHODS: Proliferation of cultured human retinal pigment epithelium (RPE) cells, with various concentrations of IFN-beta, and with or without 3% fetal calf serum (FCS), was assessed by cell counting. Effects of short (3 h) or prolonged (48 h) exposure of RPE cells to natural human IFN-beta were assessed by (3)H-thymidine uptake. Cytosolic and membranous PKC activity over time in cells treated with IFN-beta and calphostin C was also measured. RESULTS: IFN-beta inhibited the increased proliferation by FCS in the prolonged-exposure assay. The PKC inhibitor calphostin C also showed an inhibitory effect on RPE cell growth and (3)H-thymidine uptake in the chronic exposure with FCS. Short treatment with IFN-beta had no inhibitory or stimulatory effect on (3)H-thymidine uptake. Cytosolic and membranous PKC activity was strongly upregulated after short IFN-beta exposure but returned to original levels after 1 h. PKC activity was downregulated both in the cytosol and membrane after 24 or 48 h. CONCLUSION: IFN-beta inhibited RPE proliferation in vitro and the effect is mediated by upregulation of the PKC pathway.

Cell Division↗
PubMedDate not supplied

Gene transfer by adenovirus in rabbit iris sphincter muscle.

The effect of insertion of an exogenous gene on smooth muscle function in rabbit iris sphincter muscle was investigated. An adenoviral vector encoding the bacterial LacZ gene (AdLacZ, 10(7) pfu) and viscoelastics were injected into the posterior chamber of eyes of albino rabbits. Three days after injection, the effects of acetylcholine (Ach), carbachol (Carb), substance P (SP) and electrical field stimuli on isolated iris sphincter were investigated using isometric tension-recording methods. X-Gal histostaining showed that iris sphincter smooth muscle cells were transfected in 7 of 11 muscle strips. Contraction-response curves for Ach, Carb or SP were not different from control. We conclude that the iris sphincter muscle can be gene-transfected by posterior chamber infusion of an adenoviral vector with viscoelastics. Adenovirus-mediated gene transfer per se had no measurable effect on tension development.

Acetylcholine↗
PubMedDate not supplied

Effect of a cholecystokinin antagonist, proglumide, on cholecystokinin-8-induced gallbladder contraction in conscious dogs.

The objective of this study was to characterize the effect of proglumide, a cholecystokinin (CCK) antagonist, on gallbladder contraction stimulated by CCK in conscious dogs. The gallbladder contraction was monitored by a strain-gauge force transducer that was chronically sutured onto the serosal surface of the gallbladder. The results of this study show that proglumide, given as an intravenous bolus (2.5, 5, 10, 20, and 40 mg/kg) or as a continuous intravenous infusion (150 or 300 mg/kg/h, 10 min), can block the stimulatory action of CCK in a dose-related manner. Bolus administration of proglumide resulted in a transient inhibition, whereas continuous infusion of proglumide resulted in a prolonged antagonism of CCK-stimulated gallbladder contraction. Review of the data leads to the conclusion that the antagonistic action of intravenously administered proglumide on CCK-stimulated gallbladder contraction may be characterized as rapid and reversible.

Animals↗
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Positron emission tomographic evaluations in the diagnosis and therapy of multifocal glioblastoma. Report of a pediatric case.

A pediatric case of multifocal glioblastoma is reported with special reference to positron emission tomography (PET) evaluations in the diagnosis and therapy. A PET scan employing 15O and 18F positron tracers disclosed a right thalamic lesion high in regional cerebral blood flow, cerebral blood volume and metabolic glucose rate, suggesting a malignant tumor. In contrast, a left frontal lesion with low regional cerebral blood flow, cerebral blood volume and metabolic glucose rate was presumed to be rather hypodynamic and hypometabolic. Histological examination of these isolated masses showed both to be glioblastomas, and, as predicted by the PET findings, there were minor histological distinctions. In repeated PET scans following postoperative combined radiochemotherapy, metabolic glucose rate values at the thalamic tumor decreased to about 50% the levels before therapy, although there was no distinguishable change in tumor size on the concurrent computerized tomography scans. This therapeutic efficacy on tumor metabolism was highly consistent with the period of clinical relief.

Brain Neoplasms↗
PubMedDate not supplied

Production of various models of cerebral infarction in the dog by means of occlusion of intracranial trunk arteries.

Using the dog, which has been believed unsuitable for research on brain infarction because of an extensive collateral cerebral circulation, we have succeeded in producing at will ischemic foci, as determined from post-occlusion carbon perfusion, in the thalamus, cerebral mantle or entire cerebral hemisphere. This has been achieved by occlusion of various combinations of cerebral vessels at the base of the brain. A unilateral temporal approach has been used in identifying and occluding all of the bilateral trunk arteries. The following models of cerebral infarction have been made: 1) unilateral or bilateral complete cerebral hemisphere infarction, 2) unilateral or bilateral cerebral mantle infarction, 3) unilateral or bilateral thalamic infarction, 4) unilateral hemispheric and contralateral cerebral mantle infarction, 5) unilateral cerebral mantle and contralateral thalamic infarction, and 6) unilateral complete cerebral hemisphere and contralateral cerebral mantle infarction. These models of infarction in the dog can be produced with a high degree of success, and the amount of infarction can be controlled by the duration of vessel occlusion. The pathophysiology of brain infarction and brain edema following recirculation can be hemodynamically, electroencephalographically and biochemically studied using these models of cerebral infarction.

Animals↗
PubMedDate not supplied

Clinico-epidemiologic study of stroke in Akita, Japan.

An analysis was performed of 2,168 consecutive stroke patients who were examined by computed tomography and entered into a hospital-based stroke registry in Akita Prefecture, Japan. The occurrence of cerebral hemorrhage, cerebral infarction, and subarachnoid hemorrhage was 30, 55, and 14%, respectively. Age-specific rates of subarachnoid hemorrhage were higher in women than men; other types of stroke showed a preponderance in men. Total strokes increased in the winter; this seasonal difference was confined to cerebral hemorrhage. Putaminal hemorrhages predominated in the younger age groups; thalamic hemorrhage and cerebellar hemorrhage were predominant in the older age groups. The increased accuracy of the diagnosis of stroke subtypes by the use of computed tomography in this study is in contrast to other community-based epidemiologic studies that have relied solely on clinical diagnosis. This increased accuracy is seen to be the reason that new ratios of stroke subtype incidence have been identified.

Cerebral Hemorrhage↗
PubMedDate not supplied

Experimental cerebral infarction. Part 1: Production of thalamic infarction in dogs.

Difficulties in achieving focal temporary cerebral ischemia in experimental animals have delayed study of the prevention and treatment of cerebral infarction. We have succeeded in producing focal cerebral infarction by temporary occlusion of brain arteries. Infarction confined to the anterior portion of the thalamus was obtained by simultaneous occlusion of the 4 cerebral arteries: internal carotid, anterior cerebral, middle cerebral and posterior communicating arteries for 60-120 minutes. This experimental model in dogs is unique, since thalamic infarction can be produced with high frequency, and the dogs can be kept alive and managed for sufficient periods after temporary artery clipping. With this model it is possible to investigate cerebral infarction not only from the pathophysiological viewpoint, but also from the viewpoint of prevention and treatment of cerebral infarction in man.

Animals↗
PubMedDate not supplied

Experimental cerebral infarction. Part 3: Protective effect of mannitol in thalamic infarction in dogs.

Whether or not mannitol can prevent infarctions in ischemic brain tissues was investigated utilizing the thalamic infarction model in dogs. Twenty dogs were divided into equal control and mannitol treatment groups. Temporary 4 vessel clipping for 60 minutes was adopted as the standard procedure for both groups. The only difference between the groups was the administration of 2 g/kg of mannitol before the arterial occlusion. In the controls, 6 of 10 dogs showed infarctions verified by histological changes at the seventh post-ischemic day. In the mannitol group only 1 dog in 10 showed infarction. The difference is statistically significant.

Animals↗
PubMedDate not supplied

Effects of tyrosine kinase signaling inhibition on survival after cecal ligation and puncture in diet-restricted mice.

BACKGROUND: Malnutrition impairs host immunity, resulting in high mortality and morbidity due to infections. Phosphorylation of protein tyrosine kinase (PTK) is a key step in the signaling of many cellular functions, including immune cell functions. Malnutrition may affect this signaling in response to surgical insults. The aim of this study was to examine the effects of PTK inhibition on mortality in ad libitum and in diet-restricted mice after cecal ligation and puncture (CLP). Moreover, tyrosine phosphorylation of peritoneal cells from these animals was evaluated. METHODS: Survival study: Mice (n = 45) received chow, 146 g/kg per day (ad libitum) or 36.5 g/kg per day (diet-restricted), for 7 days. Two hours before CLP, one-half the mice in each group were given a tyrosine kinase inhibitor, AG 556 (3.0 mg/kg i.p.), and the others received vehicle. Survival was observed up to 7 days after CLP. Effects of AG 556 on survival with a lesser degree of malnutrition (chow 73 g/kg per day) were also examined (n = 41). Measurement of tyrosine phosphorylation: mice (n = 20) were assigned to the ad libitum and diet-restricted (chow 36.5 g/kg per day) groups. Peritoneal cells were harvested either before or 2 hours after glycogen injection. Glycogen treatment elicits polymorphonuclear neutrophil influx into the peritoneal cavity. The cells were incubated with or without N-formyl-methionyl-leucyl-phenylalanine (fMLP). Tyrosine phosphorylation in the cells was examined using flow cytometry, laser scanning cytometry, and Western blotting. RESULTS: Diet restriction significantly reduced survival compared with the ad libitum group. AG 556 treatment decreased the survival of ad libitum, but not in diet-restricted mice in both survival experiments. Stimulation of peritoneal cells with fMLP increased tyrosine phosphorylation in the ad libitum group (23% increase before glycogen and 18% after glycogen), but not in the diet-restricted group (-9% before glycogen and 3% after glycogen). CONCLUSIONS: Inhibition of tyrosine kinase signaling impairs the ability of a well-nourished host to survive CLP-induced sepsis, while having no effects on survival in diet-restricted mice. Peritoneal cells from diet-restricted animals are unable to increase PTK phosphorylation in response to stimulation, which may be the mechanism underlying impaired host defense during malnutrition.

Animals↗
PubMedDate not supplied

Atypical presentation of vertebral bone metastasis from lung cancer.

The authors describe a case of lung cancer in a 55-year-old man who complained of back pain. Initial isotopic bone scanning showed no abnormality, however, magnetic resonance (MRI) imaging revealed bone metastasis in thoracic vertebral bone. Even when there is no typical findings of metastasis in bone scintigraphy, MRI imaging would be useful if vertebral bone metastasis is suspected. MRI imaging is an important modality to evaluate extraosseous extension and marrow invasion of metastatic tumors.

Carcinoma, Large Cell↗
PubMedDate not supplied

Prophylactic chemolipiodolization for postoperative hepatoma patients.

BACKGROUND/AIMS: The efficacy of prophylactic chemolipiodolization following hepatic resection in patients with hepatocellular carcinoma was studied. METHODOLOGY: Forty-four of 67 consecutive patients with hepatocellular carcinoma who underwent hepatectomy between 1980 and 1997 were divided into two groups: group A (n = 21), in which prophylactic chemolipiodolization was performed during postoperative follow-up (2.4 times on average using a 39 mg mean dose of epirubicin or doxorubicin); and group B (n = 23), without prophylactic chemolipiodolization. The clinicopathological background and patient survival were compared retrospectively. RESULTS: There were no differences in the clinicopathological background between the two groups. Multiple intrahepatic recurrence was frequently observed in group B (P < 0.02). The recurrence-free survival rates in group A (54.4% and 31.1% at 3 and 5 years, respectively) were significantly higher than those in group B (15.7% and 7.9%, respectively). The survival rates of group A (95.2% and 80.4% at 3 and 5 years, respectively) were significantly higher than those in group B (40.1% and 22.9%, respectively). CONCLUSIONS: Our data suggest that postoperative prophylactic chemolipiodolization can be an effective treatment in reducing intrahepatic recurrence and may prolong survival for hepatocellular carcinoma patients following hepatic resection.

Aged↗
PubMedDate not supplied

Central neurogenic hyperventilation with primary cerebral lymphoma: a case report.

We report a case of a bright, alert patient with central neurogenic hyperventilation (CNH) associated with cerebral malignant lymphoma. CNH is a syndrome comprising normal or elevated arterial oxygen tension, decreased arterial carbon dioxide tension, and respiratory alkalosis in the absence of cardiac or pulmonary disease that stimulates a compensatory hyperpnea. A-72-year-old man with recurrent central nervous system lymphoma presented with hyperpnea. showing a respiratory rate over 30 per minute. He was fully awake and conscious. Routine laboratory studies and chest X-ray were normal, but arterial blood gas examination on room air showed respiratory alkalosis, regardless of wakefulness or sleep. Pulmonary infarction was denied by pulmonary flow scintigram. Rebreathing from a paper bag, intravenous administration of diazepam, and oxygen inhalation failed to alter the respiratory pattern. Brain MRI demonstrated two mildly enhanced lesions within the left side of the medulla oblongata and right side of the pons. CNH is rare in patients with normal consciousness. It seems to be caused by brainstem injury that includes the respiratory center.

Aged↗
PubMedDate not supplied

The liver as a potential hematolymphoid organ examined from modifications occurring in the systemic and intrahepatic hematolymphoid system during liver regeneration after partial hepatectomy.

In order to investigate whether or not the adult murine liver can function as one of the hematolymphoid organs, we studied the alteration of cellular characteristics in the systemic and intrahepatic hematolymphoid systems during liver regeneration after partial hepatectomy. Liver regeneration affects the systemic hematolymphoid system, as can been seen from the transient increase in colony forming unit in culture (CFU-C) frequency observed in the bone marrow at 20 hr and its gradual increase in the spleen up to the 6th day after partial hepatectomy. CFU-C were found not only in peripheral blood lymphocyte-rich fraction (PBL), but also in intrahepatic lymphocyte-rich fraction (IHL) of the normal adult liver. CFU-C frequency showed a weak increase in PBL and a dramatic increase, up to the 6th post-hepatectomy day, in IHL subfraction cells, forming a very strong liver association. Colonies, which were generated from IHL in a fibrin clot culture system, were mainly composed of granulocytes, macrophages and mast cells. Wheat germ agglutinin (WGA) positive cells too were detected in IHL and found to increase after partial hepatectomy. IHL of the normal liver were proliferated not only by IL-3 and GM-CSF but also by IL-2. The proliferative responses of IHL to these cytokines were further augmented on day 6 after partial hepatectomy. Similar results were obtained in peripheral blood and splenic lymphocyte-rich fractions. These observations, therefore, suggest that the adult murine liver has hematolymphoid cells as its component and has the function of a hematolymphoid organ closely associated with the systemic hematolymphoid system.

Animals↗
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Surgical treatment of carcinoma of the esophagogastric junction.

Forty-seven patients with carcinomas of the esophagogastric junction were operated. In acquiring complete dissection of lymph nodes located at the splenic hilus and along the splenic artery, splenectomy with or without caudal hemipancreatectomy was performed in 29 of 47 patients. To avoid leaving carcinoma cells behind in the remaining esophagus margin of resection, 20 patients underwent left thoracophrenicolaparotomy and 14 patients received blunt dissection of the intrathoracic esophagus. Five-year survival of 55.6% was observed in curative groups of the present study. No operative mortality was present.

Adenocarcinoma↗
PubMedDate not supplied

Production of granulocyte-macrophage colony-stimulating factor by adult murine parenchymal liver cells (hepatocytes).

In order to investigate the hematolymphoid system in the adult murine liver, we examined colony-stimulating factor (CSF) released from primary cultured liver cell fractions, parenchymal and nonparenchymal liver cells (more than 99% pure. Using a fibrin clot culture system, we found colony-stimulating activity not only in the culture supernatant from nonparenchymal fraction of normal liver cells (NP-NLC sup), but also in the culture supernatant from parenchymal fraction of normal liver cells (P-NLC sup). Clusters and colonies, which were generated in 4-day cultures of bone marrow cells or spleen cells with P-NLC sup or NP-NLC sup, were mainly composed of granulocytes (G), macrophages (M), and granulocytes and macrophages (GM). Both P-NLC sup and NP-NLC sup proliferated IC2, which is a GM-CSF and IL-3 dependent cell line, and this proliferation was completely inhibited by rabbit anti-murine GM-CSF antibody. Furthermore, both Northern blot analysis and in situ hybridization with specific cDNA probe for murine GM-CSF showed that parenchymal liver cells expressed GM-CSF mRNA transcripts. The present findings indicate that cultured murine parenchymal liver cells produce GM-CSF. The possibility, therefore, is suggested that parenchymal liver cells also play an important role in the regional hematolymphoid system of the liver.

Animals↗