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Biomedical subjects

K Murakami

Publications and source records attributed to K Murakami.

At least 433 records · Page 24Linked to original sources

Anticoagulant pretreatment attenuates production of cytokine-induced neutrophil chemoattractant following ischemia-reperfusion of rat liver.

We investigated whether anticoagulation would diminish ischemia-reperfusion injury of the liver. Liver ischemia was induced in rats by occluding the portal vein for 30 min. Anticoagulant was injected intravenously 10 min before occlusion. Serum concentrations of cytokine-induced neutrophil chemoattractant (CINC) in untreated rats increased following reperfusion, reaching a peak at 6 hr, then decreasing gradually to control levels by 24 hr. CINC levels in rats pretreated with heparin (50 units/kg), AT-III (250 units/kg), or DEGR-Xa (10 mg/kg) peaked at 3 hr after reperfusion and declined to baseline within 12 hr; peak CINC values were significantly lower than in untreated control rats. Expression of CINC mRNA in liver tissue paralleled the CINC serum levels. Both myeloperoxidase activity and the number of neutrophils in the liver were decreased in the anticoagulant groups. In addition, significant correlations were observed between the maximum values of AST, ALT, and LDH versus the peak CINC levels following ischemia-reperfusion. These results indicate that the release of CINC after ischemia-reperfusion of the liver is mediated by activation of coagulation within the hepatic microcirculation.

Amino Acid Chloromethyl Ketones↗

Acute gastric anisakiasis: 28 cases during the last 10 years.

Anisakiasis is a disease which occurs following eating raw fish infected with anisakis larvae. Many cases have been reported from Japan and from other countries with increasing opportunities of eating raw fish such as "sushi" and "sashimi." We have reviewed 28 patients with acute gastric anisakiasis during the last 10 years from November 1984 to October 1994. This disease has rarely been detected in persons over 60 years of age and in patients with gastric surgery. Therefore it is postulated that gastric acid secretion influences the activities of anisakis larvae. An alkaline gastric pH could interfere with the toxicity of anisakis larvae.

Adult↗

Intracranial metastases of hepatocellular carcinoma: CT and MRI.

We report clinical characteristics and CT and MRI in 16 patients with brain metastases due to hepatocellular carcinoma (HCC). Eight of these 16 patients presented with apoplexy-like symptoms (50%). Pulmonary metastases were found in 13 cases (81.3%). The mean survival from the appearance of cerebral metastases to death was 6.2 weeks, which is one of the shortest survival terms in metastatic brain tumours. Haemorrhagic brain metastases were observed in 14 patients (87.5%) with a tendency for the frequency of bleeding to increase in proportion to the size of the tumour. On both contrast-enhanced CT and MRI, metastatic brain tumours enhanced strongly, suggesting that brain metastases, like HCC, are also hypervascular. MRI is useful in evaluating brain metastases from HCC, especially in order to differentiate tumour from haemorrhage. Our results demonstrated a poor prognosis and bleeding tendency of brain metastases due to HCC and showed the usefulness of CT and MRI in achieving a correct diagnosis.

Adult↗

Stoichiometric studies of tannin-protein co-precipitation.

Co-precipitation of a series of galloylglucoses (hydrolysable tannins) with bovine serum albumin (BSA) was studied stoichiometrically by analysing both galloylglucoses and BSA in the precipitates using HPLC. BSA-precipitating ability increased mainly with an increase in the number of galloyl groups in a galloylglucose molecule but was also affected by the position of the galloyl group (penta- > tetra- > 2,3,6-tri- > 2,3,4-tri- >> di- >> monogalloylglucose). The precipitated BSA increased linearly with an increase in the number of galloyl groups bound to a BSA molecule. BSA-precipitating abilities of the galloylglucoses were closely related to their relative affinities for BSA. These results suggest a two-stage mechanism: initial complexation of galloylglucose with BSA and subsequent precipitation, as a mechanism of the co-precipitation.

Animals↗

Effect of gliclazide on the functional response to calcium in diabetic rat heart.

1. The cardiac functional response to extracellular Ca2+ in isolated working hearts was evaluated in streptozotocin-induced diabetic rats treated or not treated with gliclazide. 2. Gliclazide treatment of diabetic rats allowed a partial recovery of the body weight decrease, but not of the hyperglycemia nor insulinopenia. 3. The cardiac mechanical response of diabetic rats was altered, especially at high Ca2+ concentration, and 6-week gliclazide treatment restored the dysfunction close to the control values. 4. The results suggest that gliclazide treatment restores the cardiac function of chronic diabetic rats partly through modulating the Ca2+ metabolism.

Animals↗

Metabolite profiles in patients on high-dose valproate monotherapy.

To investigate the mechanism of valproate (VPA)-induced hepatotoxicity, we measured the serum and urine metabolites of VPA in high-dose VPA monotherapy by GC/MS/SIM and discussed the relationship between liver function and beta-oxidation, omega-, (omega-1)-oxidation metabolites and 4-en-VPA. In high-dose VPA monotherapy, the concentrations of beta-oxidation metabolites were not increased except for 2-en-VPA, but the concentrations of {omega + (omega-1)}-oxidation metabolites and of 4-en-VPA were increased about 4-5 times compared to those of standard dose VPA monotherapy. Serum GOT was not significantly correlated to 4-en-VPA and the ratio of beta-oxidation/{omega + (omega-1)} oxidation metabolites of VPA in serum. In high-dose VPA monotherapy, it is speculated that the beta-oxidation of VPA in the mitochondria reached the saturation point. However, instead of the beta-oxidation, the {omega + (omega-1)}-oxidation in microsomes was increased. We could not find significant relationship between the formation of toxic metabolites of VPA and liver dysfunction. Our data in VPA monotherapy suggest that the mechanisms of VPA-induced fatal hepatotoxicity cannot be explained by decreased beta-oxidation, increased omega-oxidation and increased 4-en-VPA level.

Adolescent↗

B-1a, B-1b and conventional B cell lymphoma from enzootic bovine leukosis.

In order to characterize the phenotypes of tumor cells and to clarify from which B cell lineage the lymphomas were derived, ten cows with enzootic bovine leukosis were examined by means of immunohistologic staining and flow cytometry. The tumor cells expressed mainly major histocompatibility complex (MHC) class II+ (10/10), BoCD11b+ (9/10), IgG1+ (8/10), B-B2+ (8/10) BoCD5+ (7/10), and lambda light chain+ (7/10). Tumor cells from only one animal expressed sIgM+ (1/10). Tumor cells from all ten animals were negative for IgG2, BoCD3, BoCD4, BoCD8, WC1-N2, and IL-2R alpha. The phenotypes of these tumor cells were all slightly different, suggesting that bovine leukemia virus (BLV)-induced lymphoma expresses phenotypic diversity. Moreover, tumor cells from seven cattle coexpressed BoCD5 and BoCD11b (B-1a cells). On the other hand, tumor cells from two of them only expressed BoCD11b (B-1b cells), and those from one were negative for both BoCD5 and BoCD11b (conventional B cells). Therefore, we concluded that BLV-induced lymphoma cells can be derived from B-1a, B-1b and conventional B cells.

Animals↗

MRI evidence of high signal intensity and temporomandibular arthralgia and relating pain. Does the high signal correlate to the pain?

In order to investigate the relationship between various temporomandibular joint (TMJ) pain levels and the detection of high signal intensity (joint effusion) on T2 weighted magnetic resonance imaging (MRI), 19 consecutive patients who complained of unilateral painful TMJ hypomobility (closed locking) were involved in this study. All patients were clinically examined in a routine manner, and all patients rated their pain levels by a visual analogue scale and eight pain questionnaire prior MRI study. T1 and T2 weighted MRI was taken in sagittal section at unilateral affected joint side. The presence or absence of a high signal intensity spot within the TMJ compartment were judged by three examiners. The high signal intensity was detected in 10 joints, but not in 9 joints. In between these two groups, the pain ratio was calculated and compared. The data showed that there was no significant statistical correlation between pain levels and the presence of high signals. This study disclosed that the MRI detection of high signal intensity in the closed locking TMJ did not directly relate to the presence of TMJ pain nor the increased pain level. These indicate the need of further larger studies.

Adolescent↗

Four-year follow-up study of temporomandibular joint arthroscopic surgery for advanced stage internal derangements.

PURPOSE: This study evaluated the long-term outcome after temporomandibular joint (TMJ) arthroscopic surgery for patients with internal derangement with stage V disease. MATERIALS AND METHODS: Fifteen female patients (24 TMJs) who underwent arthroscopic surgery were evaluated by a questionnaire preoperatively and postoperatively 3 to 5 years later (mean: 4 years, 2 months). The questionnaires consisted of a visual analog scale, pain and jaw dysfunction scores, and self-measured interincisal opening. Clinical examination and conventional radiographic evaluation were done in nine patients (13 joints). Postoperative magnetic resonance imaging was done in two patients (3 joints). RESULTS: All post-treatment scores showed a statistically significant improvement, although joint noise remained in some patients. The radiographic examination revealed mild to moderate degenerative changes, but no abnormal resorption was detected. The surgical success rate was 93.3%. CONCLUSION: Arthroscopic surgery is a useful, minimal invasive, surgical procedure for advanced stage internal derangement of the TMJ.

Adult↗

Outcome of arthrocentesis for temporomandibular joint with closed lock at 3 years follow-up.

OBJECTIVE: The aim of this study was to evaluate the intermediate term results of arthrocentesis for the management of temporomandibular joint closed lock. STUDY DESIGN: Twenty consecutive patients with closed locking of their temporomandibular joint were treated by arthrocentesis. All patients rated their pain level on a visual analogue scale, and completed pain, jaw dysfunction, and daily activity questionnaires before, 6 months, and 3 years after the procedure. The patients' jaw opening was also scaled. Preoperative and postoperative differences of the data were analyzed statistically. The success rate was also calculated according to our success criteria. RESULTS: The success rate was 70% at 6 months follow-up; it increased to 78.9% over the 3 years of follow-up. All posttreatment scores showed significant improvements in efficacy. CONCLUSION: Arthrocentesis was considered as an effective minimally invasive surgical treatment for temporomandibular joint closed lock based when evaluated 3 years after the procedure.

Adult↗

Thrombin stimulates production of interleukin-8 in human umbilical vein endothelial cells.

Interleukin-8 (IL-8) is regarded as an important mediator of inflammation because of its potent and specific chemotactic activity on neutrophils. In the present investigation, human umbilical vein endothelial cells (HUVEC) stimulated with thrombin were found to produce IL-8, in a dose- and time-dependent manner. After stimulation with 10 U/ml thrombin for 24 hr, the level of IL-8 in the conditioned medium was 14 ng/ml, or enough to elicit PMN chemotaxis in vitro. Northern blot analysis revealed that thrombin as well as IL-1 beta elevates the level of IL-8 mRNA preceding the formation of IL-8 protein. A synthetic peptide SFLLRN [human thrombin receptor-activating peptide (TRAP)] was found to mimic the action of thrombin. Preincubation with anti-thrombin compounds such as hirudin and antithrombin-III-heparin almost completely suppressed the action of thrombin without affecting the actions of other stimuli including IL-1 beta, phorbol 12-myristate 13-acetate (PMA) and TRAP. Diisopropylfluorophosphate-treated thrombin did not stimulate IL-8 production. Calphostin-C, a protein kinase C (PKC) inhibitor, attenuated the production of IL-8 by thrombin, TRAP and PMA, but left the action of IL-1 beta unchanged. These results strongly suggest that catalytic activation of thrombin receptor by thrombin results in PKC-dependent IL-8 production accompanied by an increase in IL-8 mRNA level.

Blotting, Northern↗

Structure and intracellular localization of mouse ADP-ribosylation factors type 1 to type 6 (ARF1-ARF6).

ADP-ribosylation factors (ARFs) are a family of small GTP-binding proteins that are proposed to be involved in the formation of coated transport vesicles. Although six ARF sequences have been reported in mammals to date, it has been unclear how many ARF members are present in a single organism. In this study, we provide the first direct evidence by cDNA cloning for the presence of all six ARF members in mouse. These proteins are highly conserved across mammalian species and Northern blot analysis revealed that mRNAs for all the members were expressed ubiquitously. Transfection of cells with epitope-tagged ARFs revealed that ARFs 1-3 displayed a perinuclear Golgi localization, while ARFs 4-6 appeared to be widely dispersed throughout the cytoplasm. These results suggest that although all the ARF proteins play fundamental and critical roles in cellular function, they are involved in different vesicular transport processes.

ADP-Ribosylation Factor 1↗

Gabexate mesilate, a synthetic protease inhibitor, attenuates endotoxin-induced pulmonary vascular injury by inhibiting tumor necrosis factor production by monocytes.

OBJECTIVE: In order to determine whether gabexate mesilate, a synthetic protease inhibitor with anticoagulant properties, is useful for the treatment of adult respiratory distress syndrome, we examined its effect on endotoxin-induced pulmonary vascular injury in rats. DESIGN: Prospective, randomized, controlled study. SETTING: Research laboratory at a university medical center. SUBJECTS: Male Wistar rats (180 to 220 g.) INTERVENTIONS: Animals received intravenous infusions of endotoxin (5 mg/kg iv) or saline (control). Pulmonary vascular injury was assessed 6 hrs after administration of endotoxin in terms of the increase in vascular permeability. Rats received gabexate mesilate (10 mg/kg ip), heparin, antithrombin III, an inactive derivative of activated factor X (a selective inhibitor of thrombin generation), or N-[2-[4-(2,2-dimethyl-propionyloxy) phenylsulfonylamino] benzoyl] aminoacetic acid (ONO-5046) (a potent granulocyte elastase inhibitor) 30 mins before endotoxin administration. Leukocytopenia was induced by administration of methotrexate. The effects of the gabexate mesilate on the function of activated neutrophils and the production of tumor necrosis factor -alpha (TNF-alpha) by endotoxin-stimulated monocytes were examined in vitro using neutrophils and monocytes prepared from healthy human volunteers. MEASUREMENTS AND MAIN RESULTS: Pulmonary vascular permeability was determined by measuring the vascular leakage of intravenously administered 125I-labeled bovine serum albumin. Intravenous administration of endotoxin significantly increased pulmonary vascular permeability. Gabexate mesilate significantly inhibited pulmonary vascular injury observed 6 hrs after the administration of endotoxin. Pulmonary vascular injury was not attenuated by the administration of heparin, heparin plus antithrombin III, or the inactive derivative of activated factor X, but pulmonary vascular injury was significantly attenuated in animals with methotrexate-induced leukocytopenia and in those animals treated with N-[2-[4-(2,2-dimethyl-propionyloxy) phenylsulfonylamino] benzoyl] aminoacetic acid. Gabexate mesilate in concentrations of 10(-4) to 10(-3) M inhibited the release of granulocyte elastase and leukocyte aggregation stimulated by N-formyl-methionyl-leucyl-phenylalanine and the opsonized zymosan-activated production of superoxide radical by neutrophils in vitro. Gabexate mesilate significantly inhibited the endotoxin-induced increase in the serum concentration of TNF-alpha in vivo and, at a concentration of 10(-8) M, the production of TNF-alpha by endotoxin-stimulated monocytes in vitro. CONCLUSION: Our findings suggest that gabexate mesilate attenuated endotoxin-induced pulmonary vascular injury mainly by inhibiting TNF-alpha production by monocytes, which may play a central role in sepsis-related lung injury.

Animals↗

Role of granulocyte elastase in ischemia/reperfusion injury of rat liver.

OBJECTIVE: To investigate the role of granulocyte elastase in ischemia/reperfusion injury of liver, the effect of ONO-5046, a granulocyte elastase inhibitor, was examined in ischemia/reperfusion-induced liver injury in rats. DESIGN: Prospective, randomized, controlled study. SETTING: Research laboratory at a university medical center. SUBJECTS: Male Wistar rats, weighing 220 to 280 g. INTERVENTIONS: Animals receiving continuous intravenous infusion of ONO-5046 (50 mg/kg/hr) were subjected to hepatic ischemia/reperfusion. Hepatic damage was evaluated by effects on bile formation capacity, plasma clearance of indocyanine green, and serum aminotransferase concentrations after ischemia/reperfusion. MEASUREMENTS AND MAIN RESULTS: Hepatic dysfunction, observed after 60 mins of ischemia/reperfusion, led to a reduction in bile flow and to a decrease in the plasma clearance of indocyanine green. These indicators of hepatic dysfunction were prevented, to a large extent, by administration of ONO-5046. Serum concentrations of aminotransferases increased after hepatic ischemia/reperfusion, peaking at 12 hrs of reperfusion. Increases in serum concentrations of aminotransferases were significantly inhibited by ONO-5046. CONCLUSION: Granulocyte elastase derived from activated leukocytes may play a critical role in hepatic dysfunction and the subsequent hepatic injury induced by ischemia/reperfusion.

Animals↗

Effects of nitric oxide synthase inhibition on brain infarction in SOD-1-transgenic mice following transient focal cerebral ischemia.

To investigate the role of superoxide in the toxicity of nitric oxide (NO), we examined the effect of nitric oxide synthase (NOS) inhibition on brain infarction in transgenic mice overexpressing CuZn-superoxide dismutase (SOD-1). Male SOD-transgenic mice and non-transgenic littermates (30-35 g) were subjected to 60 min of middle cerebral artery occlusion followed by 24 h of reperfusion. Either NG-nitro-L-arginine methyl ester (L-NAME; 3 mg/kg), a mixed neuronal and endothelial NOS inhibitor, or 7-nitroindazole (7-NI; 25 mg/kg), a selective neuronal NOS inhibitor, was administered intraperitoneally 5 min after the onset of ischemia. At 24 h of reperfusion, the mice were decapitated and the infarct volume was evaluated in each group. In the nontransgenic mice, L-NAME significantly increased the infarct volume as compared with the vehicle, while 7-NI significantly decreased it. In the SOD-transgenic mice, L-NAME-treated animals showed a significantly larger infarct volume than vehicle-treated ones, whereas there were no significant differences between 7-NI- and vehicle-treated mice. Our findings suggest that selective inhibition of neuronal NOS ameliorates ischemic brain injury and that both neuronal and endothelial NOS inhibition may result in the deterioration of ischemic injury due to vasoconstriction of the brain. Since L-NAME increased infarct volume even in SOD-transgenic mice, the protective effect of SOD could result from the vasodilation by increased endothelial NO as well as the reduction of neuronal injury due to less production of peroxynitrite compared to wild-type mice. Moreover, the neurotoxic role of NO might not be dependent on NO itself, but the reaction with superoxide to form peroxynitrite, because of no additive effects of SOD and a neuronal NOS inhibitor.

Animals↗

Detection of coagulating gland renin by hybridohistochemistry.

To obtain evidence of renin-synthesizing cells in the murine coagulating gland (CG), CG renin mRNA was detected by hybridohistochemistry, as well as in vitro reverse transcriptase-polymerase chain reaction (RT-PCR) in intact, castrated and testosterone-treated C57BL/6 mice. Hybridohistochemistry using paraffin sections of the kidneys and the CGs for the detection of renin mRNA was performed with digoxigenin-labelled probes. Some paraffin sections were immunohistochemically stained for renin by the peroxidase-anti-peroxidase method. Total RNA was extracted, incubated by reverse transcriptase, and amplified by PCR. In the kidneys, the immunoreactivity and the positive signals of hybridohistochemistry using an antisense probe were restricted to the same juxtaglomerular cells. In the control and at 7 days after testosterone administration to castrated mice, both renin-immunoreactivity and -hybridoreactivity were expressed by the epithelial cells in the CGs, while, in the CGs of the castrated mice and 3 days after testosterone injection of castrated animals, neither renin-immunoreactivity nor -hybridoreactivity was detected in the epithelial cells. Using RT-PCR, renin mRNA from the mice in the control and 7 days after testosterone injection of castrated was amplified, whereas, in the castrated and the 3 days after testosterone injection of castrated groups, it was not detected. The data presented here provide additional evidence that CG renin is regulated by testosterone.

Animals↗

The convergence of axon terminals from the mediodorsal thalamic nucleus and ventral tegmental area on pyramidal cells in layer V of the rat prelimbic cortex.

We investigated the ultrastructural basis of the synaptic convergence of afferent fibres from the mediodorsal thalamic nucleus (MD) and the ventral tegmental area (VTA) on the prefrontal cortical neurons of the rat by examining the synaptic relationships between thalamocortical or tegmentocortical terminals labelled with anterograde markers [lesion-induced degeneration or transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP)] and randomly selected unlabelled apical dendrites of layer V pyramidal cells in the prelimbic cortex. WGA-HRP-labelled terminals from the VTA ranged in diameter from 0.7 to 2.8 microm and established synaptic contacts with large dendritic profiles, i.e. proximal segments of apical dendritic shafts and spines from layer V pyramidal cells. Symmetrical synapses, i.e. inhibitory synapses, were more often seen than asymmetrical ones. Degenerating terminals from the MD formed asymmetrical synapses on dendritic spines or occasionally on small dendritic shafts of apical dendrites from layer V pyramidal cells, which received tegmentocortical synapses, mostly within layer III. Thalamocortical synapses were more distally distributed over common apical dendrites than tegmentocortical synapses, although some of them overlapped. The numerical density of direct synaptic inputs from the MD and VTA was low. These results suggest that fibres from the VTA exert their inhibitory effects directly on pyramidal cells in layer V via synaptic junctions with apical dendrites of these pyramidal cells, and that the tegmentocortical fibres are in an ideal anatomical position to modulate the reverberatory circuits between the MD and the prelimbic cortex.

Afferent Pathways↗

Effect of penicillin G on the electroporation of Rhodococcus rhodochrous CF222.

Suitable conditions for the introduction of bacteriophage DNA into cells of Rhodococcus rhodochrous CF222 by electroporation were established, and penicillin G was found to enhance the transfection frequency. When conditions optimal for the parental strain were applied to its colony-morphological mutants, different transfection frequencies were observed. Penicillin G enhanced the transfection frequency of smooth and mucoidal mutants but not of rough mutants.

Bacteriophages↗