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Biomedical subjects

T Urano

Publications and source records attributed to T Urano.

At least 199 records · Page 11Linked to original sources
PubMed1993

Dissociation of alpha 2-plasmin-inhibitor-plasmin complex and regeneration of plasmin activity by SDS treatment.

In order to understand the mechanism for the complex between alpha 2-plasmin-inhibitor (alpha 2-PI) and plasmin to express its specific activity on fibrin autography after SDS-PAGE, we analyzed the effects of SDS on alpha 2-PI molecule and alpha 2-PI-plasmin complex. Treatment of alpha 2-PI by SDS at the concentrations of 0.01% and 0.1% abolished the activity of alpha 2-PI to form a stoichiometric complex with plasmin, whereas it did not interfere with plasmin's activity. More interestingly, in the case of 0.01% SDS, alpha 2-PI was further cleaved to a smaller molecule. Treatment of previously formed alpha 2-PI-plasmin complex by SDS at the concentrations of both 0.01% and 0.1% dissociated the complex and expressed specific amidolytic activity against tripeptide substrate (S-2251), which activity was totally quenched by aprotinin. When alpha 2-PI-plasmin complex was treated by higher concentration of SDS for 12 hours, dissociated free plasmin's band could be observed on SDS-PAGE analysis. It is likely, therefore, that the exposure of alpha 2-PI-plasmin complex to SDS during the procedure of SDS-PAGE dissociates the complex and expresses its specific proteolytic activity in fibrin autography. These features of alpha 2-PI and its complex with plasmin are similar to those of plasminogen activator inhibitor type 1 (PAI-1) and its complex with plasminogen activators (PAs), thus they may represent some common features of the SERPINS.

Antifibrinolytic Agents↗
PubMed1993

Correlation between serotonergic measures in cerebrospinal fluid and blood of subhuman primate.

The relationship between the concentration of serotonin (5-hydroxytryptamine; 5-HT), its precursor; tryptophan (Trp) and the main metabolite 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) and blood of monkey have been studied. 5-HT, Trp and 5-HIAA underwent circadian changes in both CSF and blood. Significant correlations were found between 5-HT, 5-HIAA and Trp in CSF and blood. The significance of these findings and their relationship to the use of peripheral serotonergic system as a functional model of the central nervous system are discussed.

Animals↗
PubMed1993

Inverse association of nm23-H1 expression by colorectal cancer with liver metastasis.

The expression of nm23-H1 mRNA and protein was studied in colorectal cancers by Northern blotting and immunohistochemistry. All 21 colorectal cancers studied by Northern blotting had increased levels of nm23-H1 mRNA relative to the adjacent normal colonic mucosa. Increased nm23-H1 protein expression was also observed in all 36 colorectal cancer cases including those studied by Northern blotting. There was no significant correlation between nm23-H1 expression and tumour histology, serosal invasion, lymphatic invasion, venous invasion, or lymph node metastasis. However, the expression of both mRNA and protein was significantly lower in tumours associated with liver metastasis than in those without such metastasis. These observations indicate that the nm23 gene may play a role in the suppression of liver metastasis of colorectal cancer.

Antibodies, Monoclonal↗
PubMed1993

Immunohistochemical analysis of expression of nm23-H1/nucleoside diphosphate kinase in human thyroid carcinomas: lack of correlation between its expression and lymph node metastasis.

The nm23 gene that encodes nucleoside diphosphate (NDP) kinase has been proposed as a candidate tumor metastasis suppressor in rodent experimental carcinoma models and several types of human carcinomas. The present studies were designed to investigate, by immunohistochemical analysis, whether thyroid tissues express the nm23-H1/NDP kinase and, if so, whether the nm23-H1/NDP kinase expression is correlated to tumor metastasis suppressor potential in thyroid tumors. We found that normal thyroid epithelial cells were stained weakly but homogeneously by mouse monoclonal anti-nm23-H1/NDP kinase antibody. The staining intensity of the nm23-H1/NDP kinase in benign thyroid tumors tended to be weaker than that in normal thyroid tissues. In contrast, a series of malignant thyroid tumors expressed differently the nm23-H1/NDP kinase: the intensity of the nm23-H1/NDP kinase staining was stronger in 22 of 49 malignant tumors (45%), similar in 24 (49%), and weaker in 3 (6%) compared to that in normal tissues. The comparison of the staining intensity of the nm23-H1/NDP kinase in primary lesions of tumors with lymph node metastases and those without metastases revealed no statistically significant difference. In addition, there was also no significant difference in the nm23-H1/NDP kinase staining intensity of primary and metastatic lymph node lesions of tumors with lymph node metastases. These data indicate that the nm23-H1/NDP kinase may not be a good predictive marker for tumor regional metastatic potential in malignant thyroid tumors. We conclude that in thyroid tumors the nm23-H1/NDP kinase expression may be dissociated from metastasis suppressor activity.

Adenocarcinoma↗
PubMed1993

Detection of point mutations in the Kirsten-ras oncogene provides evidence for the multicentricity of pancreatic carcinoma.

It has been reported that multicentricity of pancreatic carcinomas extending beyond the pancreatic duct occur in 15% to 40% of patients. This has been difficult to confirm, however, with currently available histologic techniques. Mutations in the Kirsten (Ki)-ras oncogene, which can be detected frequently in pancreatic carcinomas using the polymerase chain reaction (PCR), may serve as a potential clonal marker of the cancer cells. Fifty-three patients with a histopathologic diagnosis of pancreatic carcinoma were selected for the determination of certain Ki-ras mutations through PCR. The authors identified mutations in the Ki-ras codon 12 in 46 of 53 tumors. Two of these 46 tumors had two different mutations to aspartic acid (GAT) and to valine (GTT) in Ki-ras codon 12. Another isolate had an additional mutation in Ki-ras codon 13. The detection of different mutations in the same tumor suggests that there may be multicentricity in pancreatic carcinomas and that its frequency may be as low as 6% of the carcinomas. These results imply that total pancreatectomy for eliminating tumor recurrence due to multicentricity may not be warranted.

Adenocarcinoma↗
PubMed1993

Detection of alpha-interferon in nasopharyngeal secretions and sera in children infected with respiratory syncytial virus.

We investigated the relationship between respiratory syncytial virus (RSV) antigen and interferon (IFN) in nasopharyngeal secretions (NPS) and sera obtained from 252 patients infected with RSV. A total of 146 (57.9%) of 252 patients had IFN in NPS with a mean titer of 28 units/ml and IFN was detected in 164 (71.6%) of 229 patients in the acute stage sera with a mean titer of 28 units/ml. IFN activities were neutralized with antiserum to IFN-alpha. RSV antigen in NPS decreased on Day 5 and later in parallel with the change of mean titer of IFN in NPS. IFN in NPS was detected in 40 to 60% of the samples with some fluctuation in the acute stage. Within 4 days IFN was detected in more than 70% of the sera whereas on Day 5 and later the IFN positivity rate decreased in sera. RSV antigen in NPS decreased in the older patient groups. No significant change of positive rate of IFN in NPS was observed in different age groups and the mean titer of IFN in NPS and sera did not vary with age, except in those younger than 3 months and older than 3 years of age.

Age Factors↗
PubMed1993

Expression of nm23-H1 and nm23-H2 proteins in prostate carcinoma.

The nm23 gene products/nucleoside diphosphate (NDP) kinase expression in prostate carcinomas and benign hyperplasias was evaluated immunohistochemically. Monoclonal antibodies against nm23-H1 and nm23-H2 proteins were prepared using the corresponding proteins fused with glutathione S-transferase as immunogens. Of the 80 cases of nonmetastatic prostate carcinoma examined, 74% (59/80) and 60% (48/80) were immunoreactive for nm23-H1 or nm23-H2 protein, respectively. Negative staining for nm23-H1 occurred in 83% of metastatic lesions, while 34% were negative for nm23-H2. All primary tumors corresponding to the metastases examined showed positive immunostaining for nm23-H1, indicating an inverse relationship between expression of this protein and metastatic status. nm23-H2 protein was detected in 83% of primary tumors and its expression appeared to be significantly correlated to the degree of histological differentiation. In contrast, all cases of benign prostatic hyperplasia showed elevated levels of both nm23-H1 and nm23-H2 expression. These data suggest that the nm23/NDP kinase may play a role in suppressing the expression of malignant potential in prostate carcinomas.

Adenocarcinoma↗
PubMed1993

Impaired fibrinolysis in hypertension and obesity due to high plasminogen activator inhibitor-1 level in plasma.

In order to elucidate the influence of the risk factors of coronary heart disease on the fibrinolytic activity, relationships between blood pressure, body mass index (BMI), plasma lipoprotein (a) (Lp(a)) level and the plasma levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) were analyzed in the subjects with mild hypertension. Systolic blood pressure showed a positive correlation with total PAI-1 and free PAI-1. Diastolic blood pressure showed no correlation with these proteins involved in the fibrinolytic system. BMI had a positive correlation with total PAI-1, free PAI-1 and euglobulin clot lysis time (ECLT). Plasma Lp(a) level showed correlation with neither blood pressure nor fibrinolytic parameters, but it showed weak negative correlation with body mass index (BMI). These results suggest that high blood pressure and obesity tend to increase free PAI-1 which reduces fibrinolytic activity. Lp(a), however, seems not to influence directly the fibrinolytic system but may work to decrease fibrinolytic activity only in conjunction with other risk factors. The effects of daily drinking of alcohol and smoking on the fibrinolytic system were also investigated in the present study and we obtained the results that habitual drinking increased plasma levels of both tPA and PAI-1 whereas smoking did not affect fibrinolytic activity. These results suggest that risk factors for coronary heart disease such as hypertension and obesity are closely related to the impaired fibrinolysis.

Adult↗
PubMed1993

Serotonergic measures in blood and brain and their correlations in rats treated with tranylcypromine, a monoamine oxidase inhibitor.

Tranylcypromine, a monoamine oxidase inhibitor, was administered to male Wistar rats in order to investigate its effects on blood and brain serotonin related substances after 1, 4, and 24 h following injection and possible relations between serotonergic measures in central nervous system and periphery. The dose of the drug tested was responsible for an increase in blood serotonin with a simultaneous fall in its metabolite 5-hydroxyindoleacetic acid (5-HIAA) compared to either pretreatment or control values. These changes were the most marked after 4 and 24 h following tranylcypromine injection. Almost all brain areas studied (cerebellum, medulla, hypothalamus, striatum, midbrain, hippocampus, and cortex) were to be affected by monoamine oxidase inhibitor treatment. They exhibited a rise in serotonin content starting from 1 h after drug administration and lasted in many parts of the brain up to 24 h, which was accompanied by a parallel fall in 5-HIAA level. All these changes were significant when compared to baseline and control values. Alterations in blood serotonin correlated positively with changes in brain serotonin and negatively with brain 5-HIAA, while the opposite pattern of correlations was found regarding blood 5-HIAA and the content of serotonin and 5-HIAA in various brain areas studied. This pattern of correlations speaks in favor of an existence of mutual relations between blood and brain serotonin related substances. Our results suggest that blood serotonin and 5-HIAA may serve as an index of monoamine oxidase inhibitor action on the central serotonergic system.

Animals↗
PubMed1993

Correlation of p53 expression and proliferative activity in gastric cancer.

We analyzed immunohistochemically the association between p53 tissue status and prognostic parameters of 357 gastric cancer patients, using endoscopically obtained biopsy materials, embedded in paraffin. Using PAb1801, an anti-p53 monoclonal antibody p53 immunoreactivity was detected in the nuclei of cancer cells in 113 cases (32%). The nuclear p53 immunoreaction was closely associated with positive lymph node metastasis, serosal invasion, and liver metastasis. For the estimation of proliferative activity, proliferating cell nuclear antigen (PCNA) labeling rates (LRs) of biopsy specimens were immunohistochemically measured. A significant positive correlation was found between PCNA LRs and p53 tissue status. In addition, a positive nuclear p53 immunoreaction was found to be significantly associated with shorter overall survival. Especially, in the group of patients with stages III and IV, the prognosis of patients with p53-positive tumours was significantly poorer than that of patients with p53-negative tumours. These results indicate that immunohistochemical staining for nuclear p53 in biopsied materials may be useful in deciding the therapeutic schedule of patients with gastric cancer, preoperatively.

Antibodies, Monoclonal↗
PubMed1993

[Measurement of myeloperoxidase and thiobarbituric acid-reactive material in plasma and bronchoalveolar lavage in E. coli-induced acute lung injury].

Myeloperoxidase (MPO), which is exclusively contained in neutrophils, is released on their activation. Therefore, MPO may possibly be used as a parameter of neutrophil activation. Thiobarbituric acid-reactive material (TBARM) reflects lipid peroxidation and is a parameter of oxygen radical-mediated cell membrane damage. Using our guinea pig model of septic lung injury we measured MPO and TBARM in the setting of acute lung injury. The two experimental groups were saline controls (n = 8) and an E. coli septic group to which 2 x 10(9) live E. coli were administered intravenously (n = 8). Lung damage was assessed by measuring wet to dry lung weight ratio (W/D) and lung tissue to plasma accumulation of 125I-albumin (AL: albumin leakage). We measured MPO and TBARM in plasma and BAL fluid. Increased W/D and AL were observed in the E. coli group suggesting the development of acute lung injury. In the E. coli group, plasma MPO increased and MPO in BAL fluid was significantly increased as compared with the saline control group. There was no difference in plasma TBARM between the two groups, while TBARM in BAL fluid of the E. coli group was greater than in that of controls. Although BAL fluid TBARM correlated with both W/D and AL, there was no relation between BAL fluid MPO and either of these parameters. We conclude that TBARM in BAL fluid may be useful for assessing E. coli-induced acute lung injury in guinea pigs.

Animals↗
PubMed1993

Serotonin as a factor involved in pathophysiology of thromboangiitis obliterans.

Whole blood and plasma levels of serotonin (5-hydroxy-tryptamine, 5-HT) as well as its uptake and spontaneous release from blood platelets were studied in 20 patients suffering from thromboangiitis obliterans (TAO, Buerger's disease) and 20 healthy subjects matched in pairs for age. Results of patients suffering from thromboangiitis obliterans differed in several ways from those of controls. Whole blood 5-HT content was significantly lower in the group of patients compared to that of the control group. It was established that patients with Buerger's disease have significantly greater plasma concentrations of free serotonin. In Buerger's disease patients, maximal platelet serotonin uptake velocity (Vmax) was significantly decreased. It was associated with the enhanced spontaneous release of 5-HT from blood platelets. We conclude that impaired platelet serotonin uptake and increased local concentration of serotonin in the vicinity of platelets in Buerger's disease may lead to platelet activation via 5-HT2 receptors, and it could be involved in the pathogenesis of thromboembolic complications.

Adult↗
PubMed1993

Monitoring both serum amyloid protein A and C-reactive protein as inflammatory markers in infectious diseases.

We examined serum amyloid protein A (SAA) and C-reactive protein (CRP) as inflammatory markers of viral and bacterial infections. Both acute-phase reactants increased in the acute stage and thereafter decreased in the convalescent stage. In viral infections, the mean serum concentrations of SAA during the acute stage were 141 mg/L in infections with adenovirus, 77 mg/L with measles virus, 63 mg/L with influenza virus, 55 mg/L with parainfluenza virus, 31 mg/L with respiratory syncytial virus, and 31 mg/L in aseptic meningitis. The mean serum concentration of CRP was 19 mg/L for adenovirus infection and < 7 mg/L in all other viral infections. The SAA concentrations were 5- to 11-fold greater than the CRP concentrations. Both the SAA and the CRP concentrations were higher in bacterial infections than in viral infections. Changes in the concentrations of serum SAA paralleled those in serum CRP in bacterial infection; during the course of viral infection, however, serum SAA tended to disappear more quickly than CRP did. SAA appears to be a clinically useful marker of inflammation in acute viral infections, with or without significant changes in the CRP concentration.

Bacterial Infections↗
PubMed1993

Expression of nm23/NDP kinase proteins on the cell surface.

We determined whether proteins encoded by the nm23/nucleoside diphosphate (NDP) kinase gene, a potential metastasis-suppressor gene, are expressed on the cell surface. Monoclonal antibodies (mAb) specific for nm23-H1 or H2 proteins were prepared using the corresponding fusion proteins with glutathione S-transferase (GST) as immunogens. mAb H1-229 was specifically reactive with nm23-H1 protein, whereas mAb H2-439 was specific for nm23-H2 protein in immunoprecipitation and immunoblotting. mAb H1-229 was reactive with most human hematopoietic and some non-hematopoietic cell lines in flow cytometry. On the other hand, mAb H2-439 was reactive with only a limited number of cell lines. Based upon the surface expression of nm23/NDP kinase, cells were classified as nm23-H1+H2-, nm23-H1+H2+ or nm23-H1-H2-. No cell lines with nm23-H1-H2+ were found among those examined. The specificity of flow cytometry analysis was confirmed in the murine myeloma line NS-1 transfected with either the nm23-H1 or H2 genes. Both mAbs were reactive only to NS-1 transfected with the corresponding nm23 genes. Immunoprecipitation and SDS-PAGE analysis identified 20.5- and 18-kDa proteins with mAb H1-229 or H2-439, respectively, in cellular extracts of 125I-surface labeled NS-1 transfected with the corresponding genes. The presence of nm23/NDP kinase on the cell surface indicates an extracellular role for these proteins in addition to their reported intracellular functions.

Animals↗
PubMed1992

trans-5-prostaglandin E2 stimulates plasminogen activation by tissue-type plasminogen activator.

The effect of trans-5-prostaglandin E2 (trans-PGE2) on fibrinolysis was examined in vitro using synthetic chromogenic substrate S-2251. trans-PGE2 was found to enhance plasminogen (PLG) activation mediated by tissue-type plasminogen activator (tPA). The enhancing effect was dependent on the concentration of trans-PGE2. cis-PGE2 and the other PGs (PGE1 and PGI2) did not show such an effect as trans-PGE2, despite to the fact that their structures are similar to that of trans-PGE2. trans-Configuration around the double bond at the 5-position seems to be important in the enhancement of the fibrinolytic activity.

Amino Acid Sequence↗
PubMed1992

A substrate-like form of plasminogen-activator-inhibitor type 1. Conversions between different forms by sodium dodecyl sulphate.

Recombinant plasminogen-activator-inhibitor type 1 (PAI-1) purified in an active form from Escherichia coli and eucaryotic cells was found to contain a mixture of three functionally distinct forms: an active form that forms complexes with plasminogen activators (PAs), an inactive (latent) form that remains intact after incubation with PAs, and a substrate-like form which is easily cleaved by PAs. Since active PAI-1 purified from bacteria (rpPAI-1) contains only trace amounts of the inactive latent and the substrate-like forms, this material was used to study the effect of sodium dodecyl sulphate (SDS) on the structure and function of active PAI-1. After treatment with 0.01% SDS, active rpPAI-1 was converted to an inactive form that did not form complexes with PAs, but exhibited characteristics similar to those of latent PAI-1. After treatment with 0.1% SDS, PAI-1 lost its inhibitory activity and was cleaved as a substrate in the reactive center. Circular dichroism spectral analysis reveals that SDS changed the conformation of PAI-1 dramatically, mainly by increasing its alpha-helical content.

Amides↗