A problem with the diagnosis of diabetes mellitus based on fasting plasma glucose.
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Blood Glucose↗
Biomedical subjects
Y Sato
Publications and source records attributed to Y Sato.
The efficacy of acetic acid for glycogen repletion in rat skeletal muscle after exercise.
We examined the effect of acetic acid, the main component of vinegar, on glycogen repletion by using swimming-exercised rats. Rats were trained for 7 days by swimming. After an overnight fast, they were subjected to a 2-hr swimming exercise. Immediately afterward, they were given by gavage 2 ml of one of the following solutions: 30 % glucose only or 30 % glucose with 0.4 % acetic acid. Rats were sacrificed by decapitation before, immediately after exercise and 2 hours after the feeding. Exercise significantly decreased soleus and gastrocnemius glycogen content, and feeding significantly increased liver, soleus and gastrocnemius glycogen content. In soleus muscle, acetate feeding significantly increased glycogen content and the ratio of glycogen synthase in the I form (means +/- SEM: 4.04 +/- 0.41 mg/g-tissue and 47.0 +/- 0.7 %, respectively) in contrast to no acetate feeding (3.04 +/- 0.29 mg/g-tissue and 38.1 +/- 3.4 %, respectively). Thus, these findings suggest that the feeding of glucose with acetic acid can more speedily accelerate glycogen repletion in skeletal muscle than can glucose only.
Acetic Acid↗
Augmented binding and activation of latent transforming growth factor-beta by a tryptic fragment of latency associated peptide.
Transforming growth factor-beta (TGF-beta) is secreted in a latent form; thus, activation is critical for the control of TGF-beta action. Latent TGF-beta exists in a complex in which mature TGF-beta is noncovalently linked to latency associated peptide (LAP) and latent TGF-beta binding protein (LTBP) complex. We have shown that latent TGF-beta is efficiently activated in heterotypic cultures of endothelial cells (ECs) and smooth muscle cells (SMCs). Under those conditions, LAP plays an important role in targeting latent TGF-beta to the surface of SMCs, and plasmin and calpain target it to the surface of ECs for activation. Here, we demonstrate in a homotypic culture system that fragments of LAP increase the binding of latent TGF-beta to ECs, resulting in its activation by cell-associated proteolysis. LAP fragments appear to bind to the cell surface and augment the binding of latent TGF-beta, independent of transglutaminase. These results suggest a unique mechanism for the activation of latent TGF-beta by proteolytic fragments of LAP. The mechanism may arise from degradation by elevated levels of proteases under certain conditions.
Amino Acid Sequence↗
Serum cardiac troponin T and plasma brain natriuretic peptide in patients with cardiac decompensation.
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Aged↗
Detection of genes expressed in primary colon cancers by in situ hybridisation: overexpression of RACK 1.
AIMS: The isolation of various genes that are expressed in a region specific manner is considered useful for research in molecular pathology. In situ hybridisation (ISH) was used in a screening procedure to isolate these genes efficiently, using colon cancer as a model. METHODS: Suppression subtractive hybridisation (SSH) between colon cancer tissue samples and corresponding non-cancerous tissues was performed. Genes showing high expression in the cancers were selected using macro-DNA array analysis. As a final screening procedure, conventional ISH was performed to isolate genes expressed specifically in colon cancers. RESULTS: Sixty nine clones were selected by SSH and macro-DNA array analyses. These clones were then analysed by ISH to examine their expression patterns. ISH screening revealed that all the clones screened showed more intense signals in colon cancers than in non-cancerous tissues. Among them, RACK 1, which is a protein kinase C receptor and a homologue of the G protein beta subunit, was expressed intensely in colon cancer cells. RACK 1 expression was evaluated in multiple samples by ISH, and the results confirmed that RACK 1 was universally overexpressed in cells of all 11 colon cancers examined. CONCLUSIONS: Many genes, including RACK 1, expressed in colon cancer cells can be isolated efficiently by this method, and their precise expression pattern can be evaluated. These results indicate that ISH is an excellent technique for systemic screening of genes expressed in a region specific manner.
Blotting, Northern↗
Ocular angiostrongyliasis without meningitis symptoms in Okinawa, Japan.
A 62-year-old female farmer presented with retinal detachment in her left eye, and an Angiostrongylus cantonensis worm was recovered by vitreous surgery. The case did not show typical clinical symptoms indicating meningitis, although the patient complained of a mild headache, a low-grade fever, and slight ataxia. The symptoms were treated as influenza before the onset of the retinal detachment. The present case is the first confirmed of ocular angiostrongyliasis in Japan.
Angiostrongylus cantonensis↗
Time-dependent potentiation of the beta-cell is a Ca2+-independent phenomenon.
When isolated rat pancreatic islets are treated with 16.7 mM glucose, a time-dependent potentiation (TDP) of insulin release occurs that can be detected by subsequent treatment with 50 mM KCl. It has been thought that TDP by glucose is a Ca2+-dependent phenomenon and only occurs when exposure to glucose is carried out in the presence of Ca2+. In contrast to this, we now demonstrate TDP under stringent Ca2+-free conditions (Ca2+-free buffer containing 1 mM EGTA). In fact, under these Ca2+-free conditions glucose caused an even stronger TDP than in the presence of Ca2+. TDP induced by glucose in the absence of extracellular Ca2+ was unaffected by inhibitors of protein kinase C (PKC). However, cerulenin or tunicamycin, two inhibitors of protein acylation, eradicated TDP without affecting glucose metabolism. The TDP by glucose was not associated with an increase in the cytosolic free Ca2+ concentration ([Ca2+]i) during subsequent treatment with high K+. Exposure of islets to forskolin under Ca(2+)-free conditions did not cause TDP despite a large increase in the cellular cAMP levels. In conclusion, glucose alone induces TDP under stringent Ca2+-free conditions when [Ca2+]i was significantly lowered. Protein acylation is implicated in the underlying mechanism of TDP.
Acylation↗
[Surgery for synchronous primary lung cancers and intrapulmonary metastases].
Between 1988 and 2000, 1,040 patients with primary lung cancer underwent pulmonary resection at Nagaoka Red Cross Hospital. Thirty-one (2.9%) patients had synchronous primary lung cancer (group A) and 78 patients (7.5%) had intrapulmonary metastases (group B). The 5-year and 10-year survival rate for group A was 64% and 56% respectively and for group B 37% and 32% respectively. The patients in group A showed a better survival rate in the different lobes (80% at 5 years) than in the same lobe (55%), while those in group B gave reverse results (31% and 42%). In group A, the patients had a better survival rate in the different histology (73% at 5 years) than in the same histology (45%). The 5-year survival was 65% for 20 patients with stage I disease, 75% for 4 patients with stage II disease, 43% for 75 patients with stage III and 25% for 10 patients with stage IV. These data suggest that synchronous primary lung cancer had a better prognosis than primary lung cancer with satellite nodules, but the histological discrimination between multiple lung cancers and intrapulmonary metastases was uncertain.
Adult↗
Peripheral pulmonary atelectasis and oxygentation impairment following coronary artery bypass grafting.
BACKGROUND: Severe pulmonary oxygenation impairment occurred in some patients with pleurotomy during the harvest of the internal mammary artery graft followed by coronary artery bypass grafting (CABG). Peripheral pulmonary atelectasis in the postoperative chest X-ray was detected in these patients. We studied the efficacy of intraoperative positive end-expiratory airway pressure (PEEP) therapy for the prevention of postoperative pulmonary oxygenation impairment. METHODS: The pleural cavity was intraoperatively opened in 40 patients with solitary CABG procedure performed during 5 years since January 1992. These patients were divided into two groups. Intraoperative PEEP therapy, which is initiated just after pleurotomy, was not used in 32 patients before May, 1996 (control group) and used for recent 8 patients with pleurotomy (PEEP group). The mean age of patients was 60 years old in the control group and 68 in the PEEP group. RESULTS: Respiratory insufficiency (A-aDO2 >400 mmHg and RI >1.5) was detected in 6 patients in the control group. Three out of these 6 patients required long-term mechanical respiratory support over a week. No respiratory insufficiency occurred in patients of the PEEP group. Values of PaO2, A-aDO2, respiratory index and shunt ratio were significantly worse in the control group than in the PEEP group. CONCLUSIONS: In conclusion, PEEP therapy may prevent pulmonary atelectasis and oxygen impairment after CABG.
Aged↗
[Resection for pulmonary metastasis of gastrointestinal stromal tumor of the stomach at 10 years after gastrectomy; report of a case].
A 70-years-old male, who had received gastrectomy for leiomyosarcoma of the stomach 10 years ago, was found to have a left lung tumor on chest X-ray and computed tomography (CT). The tumor was diagnosed to be a pulmonary metastasis of gastric leiomyosarcoma. On admission, another tumor was detected at left occipital region by brain CT and was thought to be meningioma. Left lower lobectomy and brain tumor resection were performed serially. The histologic and immunohistochemical findings showed that both tumors were metastases of gastrointestinal stromal tumor (GIST) of the stomach after long disease-free interval. Compared with the primary tumor, cellular density, mitotic figures, bizarre nuclei, and necrotic foci were prominent in the metastatic tumors. This case suggest that GIST may recurrent as pulmonary metastasis after long disease-free interval and should be follow up longer after resection. Patient prognosis with pulmonary metastases is considered to be reflected more exactly in biological malignant potential of metastatic tumor rather than that of primary tumor.
Aged↗
Effect of phosphodiesterase III inhibitor (Olprinone) on thoracic duct lymph flow in anesthetized sheep with experimentally induced heart failure by endothelin-1.
We investigated the short-term effects of a phosphodiesterase III inhibitor (Olprinone) on hemodynamics and thoracic duct lymph flow in anesthetized open-chest sheep with heart failure induced by endothelin-1 (cardiogenic shock). Ultrasound transit-time flow probes were attached to the thoracic duct, the ascending aorta and the renal artery. Arterial, pulmonary and central venous pressures were monitored. Endothelin-1 was infused intravenously at a dosage that reduced cardiac output to 50% or more of baseline (n=11). The effects of Olprinone were examined (n=5) by intravenous infusion after endothelin-1 administration. Other sheep (n=6) were used as controls. Olprinone significantly increased cardiac output that had been decreased by endothelin-1 and further increased thoracic duct flow that had been increased by endothelin-1. Increased arterial and pulmonary pressures induced by endothelin-1 administration were rapidly decreased by Olprinone. Renal arterial flow and central venous pressure were, however, unchanged by Olprinone. Overall, Olprinone acutely improved experimental cardiogenic shock (heart failure) induced by endothelin-1, and maintained thoracic duct lymph flow at a high level after endothelin-1 administration.
3',5'-Cyclic-AMP Phosphodiesterases↗
Involvement of Ca2+ waves in excitation-contraction coupling of rat atrial cardiomyocytes.
Two-dimensional and line-scan analyses of the early phase Ca2+ transients in rat cardiomyocytes were performed with a rapid-scanning laser confocal microscope and fluo-3 to elucidate the mechanism of activation of Ca2+ release from the sarcoplasmic reticulum in atrial myocytes which lack a well developed T-tubular network. On electrical stimulation of ventricular myocytes, Ca2+ concentration began to rise earliest at the Z-line level and became uniform throughout the cytoplasm within about 10 msec. In contrast, on stimulation of atrial myocytes, the earliest rise in Ca2+ occurred at the cell periphery and then spread to the cell interior; cytoplasmic Ca2+ became uniform after more than 30msec. The velocity of the propagation of rise in Ca2+ was 112 +/- 5.1 microm/sec (n = 10), which was similar to that of spontaneous Ca2+ waves observed in atrial and ventricular myocytes. No difference in frequency, amplitude and kinetics of spontaneous Ca2+ sparks was observed between the subsarcolemmal and central regions of atrial myocytes. Ryanodine concentration-dependently decreased the contractile force of isolated rat atrial and ventricular tissue preparations; the sensitivity was higher in atrial myocytes. The present study visualized the involvement of a propagated Ca2+-induced-Ca+ release mechanism in atrial but not ventricular myocytes. This difference may underlie some of the atrioventricular difference in response to physiological and pharmacological stimuli.
Animals↗
Expression of p53 and human herpesvirus-8 (HHV-8)-encoded latency-associated nuclear antigen with inhibition of apoptosis in HHV-8-associated malignancies.
BACKGROUND: Kaposi sarcoma (KS) and primary effusion lymphoma (PEL) cells express human herpesvirus-8 (HHV-8)-encoded latency-associated nuclear antigen (LANA) (open reading frame [ORF] 73 protein), suggesting that LANA plays an important role in the pathogenesis of HHV-8-associated malignancies. Recently, the binding of LANA to p53 was demonstrated in vitro. In the current study, the authors investigated the association between p53 and LANA expression with apoptosis in HHV-8-associated malignancies in vivo. METHODS: Twenty-six cases of KS, 1 case of HHV-8-associated solid lymphoma, 2 PEL cell lines, and an HHV-8-associated lymphoma engrafted in severe combined immunodeficiency (SCID) mice were examined. Immunohistochemistry using the catalyzed signal amplification system was employed to detect LANA and p53 on paraffin embedded tissues and the immunofluorescence technique was used on cell lines. To detect apoptosis, the TdT-mediated dUTP nick end labeling (TUNEL) method was used. For mutation analysis of p53, exons 5-9 of the p53 gene were amplified by polymerase chain reaction and examined by direct sequencing. RESULTS: Immunohistochemistry revealed that LANA and p53 were expressed in the tumor cells of all these specimens, and apoptotic cells were rarely detected in them using the TUNEL method. Immunofluorescence assay revealed that LANA colocalized with p53 in the nuclei of PEL cells. Sequencing analysis indicated that there was no mutation in the deduced amino acid sequences of p53 in KS tissues. CONCLUSIONS: These data suggest colocalization of p53 and LANA and the inhibition of apoptosis in HHV-8-associated malignancies in vivo, supporting the results found in vitro that p53 inhibition by LANA suppresses cell death, as reported previously. These results also suggest that the p53 pathway is crucial in the pathogenesis of HHV-8-associated malignancies.
Acquired Immunodeficiency Syndrome↗
Critical role of the neuronal nitric-oxide synthase heme proximal side residue, Arg418, in catalysis and electron transfer.
Nitric oxide (NO) is synthesized from L-Arg in the P450-type heme active site of nitric-oxide synthase (NOS). The internal axial ligand of the heme, Cys415, may hydrogen-bond to the side chain of the conserved Arg418 residue in neuronal NOS (nNOS). To understand the role of Arg418, we generated the nNOS mutants, Arg418Ala and Arg418Leu. NO formation activities with the mutants using both L-Arg and NHA as substrates were less than 0.1 nmol/min/nmol heme, in contrast to rates of 34-35 nmol/min/nmol heme with the wild-type enzyme. The heme reduction rate of the mutants was very slow, less than 10(-2) min(-1), in contrast with that (more than 10 min(-1)) of the wild type. The backbone amide group of Arg418 interacts with the Cys415 thiolate through van der Waals contact, whereas the carbonyl oxygen of Cys415 and the guanidino N(epsilon) atom of Arg418 form a tight hydrogen bond. The results suggest that Arg418 is critical in preserving the heme proximal structure and thus, is indirectly involved in both catalysis and electron transfer from the reductase domain to the heme.
Amino Acid Sequence↗
Normalization of elevated hepatic 8-hydroxy-2'-deoxyguanosine levels in chronic hepatitis C patients by phlebotomy and low iron diet.
Accumulation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in DNA, which may result from the continuous reactive oxygen species (ROS) generation associated with chronic inflammation, has been reported in various human preneoplastic lesions and in cancerous tissues. However, no direct causative relationship between the 8-OHdG formation and carcinogenesis has been thus far demonstrated in humans. Directly proving the causality requires showing that depletion of 8-OHdG levels in tissue by interfering with ROS generation results in a reduction in cancer. Chronic hepatitis C virus (HCV) infection is associated with a high risk of hepatocellular carcinoma (HCC). Several studies on patients with chronic HCV have shown that hepatic iron overload is attributable to liver injury and that iron depletion improved serum aminotransferase levels. Excess iron is known to generate ROS within cells, which causes mutagenic lesions, such as 8-OHdG. In this study, therefore, we have evaluated whether therapeutic iron reduction (phlebotomy and low iron diet) with a long-term follow-up (6 years) would decrease the hepatic 8-OHdG levels and the risk of HCC development in patients with chronic HCV. Patients (34) enrolled were those who had undergone standard IFN therapy but had no sustained response. Quantitative immunohistochemistry using the KS-400 image analyzing system and electrochemical detection was used for 8-OHdG detection. With this treatment, elevated hepatic 8-OHdG levels in patients with chronic hepatitis C (8.3 +/- 4.6/10(5) dG) significantly decreased to almost normal levels (2.2 +/- 0.9/10(5) dG; P < 0.001) with concomitant improvement of hepatitis severity, including fibrosis, whereas HCV titers were unaffected. None of these patients developed HCC. Thus, long-term iron reduction therapy in patients with chronic hepatitis C may potentially lower the risk of progression to HCC.
8-Hydroxy-2'-Deoxyguanosine↗
Induction of immunity in peripheral tissues combined with intracerebral transplantation of interleukin-2-producing cells eliminates established brain tumors.
Cytokine gene therapy for the induction of potent immune responses against central nervous system tumors has proven to have significant potential. However, this strategy needs improvement in the process of antigen presentation and/or insufficient recruitment of immunocompetent cells to achieve successful eradication of established brain tumors. We investigated the therapeutic potential of induced systemic immunity in peripheral tissues combined with interleukin-2 (IL-2) production in the vicinity of brain tumors to treat established brain tumors. Sequential magnetic resonance image monitoring showed that the combinatory therapy consisting of intracerebral (i.c.) transplantation of IL-2-producing rat gliosarcoma 9L (9L/IL-2) cells and s.c. vaccination using irradiated 9L or 9L/IL-2 cells could cure 9L-bearing rats, whereas either the i.c. injection of 9L/IL-2 cells or the s.c. vaccination produced little or marginal antitumor effects, respectively. Xenogeneic murine neuroblastoma cells secreting IL-2 could substitute for 9L/IL-2 cells, producing significant antitumor effects in the vaccinated rats. Tumor-specific cytotoxic activity was induced in the vaccinated rats but not fully in the rats treated only with i.c. injection of 9L/IL-2 cells. Immunohistochemical analysis revealed that a number of CD4(+) and CD8(+) T cells infiltrated into the brain tumors which were treated with the combinatory therapy. The level of cell infiltration was similar to that found in s.c. 9L/IL-2 tumors which were subsequently rejected. In contrast, the brain tumors treated with either i.c. transplantation of 9L/IL-2 cells or the s.c. vaccination showed only moderate infiltration of T cells. The combinatory strategy, i.c. grafting of IL-2-producing cells, and s.c. immunization of irradiated whole tumor cell vaccine, is, thus, effective for recruiting activated T cells into the brain tumor site and could be a potential therapy for brain tumors.
Animals↗
Enhanced Hoffman-reflex in human soleus muscle during exposure to microgravity environment.
Responses of Hoffman-reflex in the soleus muscle to changes of gravity levels created by parabolic flight of a jet airplane were investigated in four healthy male subjects. The subjects maintained a sitting position with seat belts fastened, keeping the anterior ankle and posterior knee angles at approximately 135 degrees. The gravity levels were altered from 1- to 2-G, and then microgravity was created for approximately 20 s. The levels were recovered from 1.5- to 1-G during the descending phase. The time interval between the stimulation and either M- or H-wave was not influenced by the changes in gravity levels. The amplitude of the M-wave during hyper- and microgravity was identical to that obtained at 1-G. However, the H-wave amplitude was increased when the subjects were exposed to microgravity (approximately four times vs. 1-G level). The H/M ratio was also elevated during microgravity. Further, such a phenomenon was maintained throughout the 20 s of microgravity exposure. Hypergravity at 1.5- or 2-G had no effect on the H-wave amplitude. It is suggested that an acute exposure to microgravity increases the excitability of the soleus motor pool and the increased excitability is restored immediately when the gravity level is elevated.
Adult↗
Interleukin-1beta stimulates galectin-9 expression in human astrocytes.
Galectin-9 is an eosinophil chemoattractant produced by activated T lymphocytes. We have addressed expression of galectin-9 in normal human astrocytes in culture. Expression of galectin-9 mRNA and protein were examined by reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and immunofluorescent staining. Interleukin-1beta (IL-1beta) was found to enhance the galectin-9 expression in time- and concentration-dependent manners. Galectin-9 protein was detected in the membrane fraction, 105 000 x g precipitate, and immunofluorescent staining revealed diffuse cellular and perinuclear distributions. Dexamethasone pretreatment almost completely suppressed the production. We conclude that astrocytes produce galectin-9 in response to the stimulation with IL-1beta, and this may contribute to inflammatory reactions in the CNS.
Anti-Inflammatory Agents↗