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Biomedical subjects

K Inada

Publications and source records attributed to K Inada.

At least 163 records · Page 9Linked to original sources

Relationship between plasma levels of type II phospholipase A2, PAF acetylhydrolase, endothelin-1, and thrombomodulin in patients with infected burns.

The relations between type II phospholipase A2 (PLA2) and PAF acetylhydrolase (PAFAH) levels and those of endothelin-1 (ET-1) and thrombomodulin (TM) were examined in samples containing the maximum amount of TNF-alpha detected over the clinical course for each patient with burn wound infection. The study included 23 patients with a total burn surface area of > 20%. Plasma levels of tumor necrosis factor-alpha (TNF-alpha), type II PLA2, PAFAH, TM, and ET-1 were 174.1 +/- 239.5 pg/ml, 229.5 +/- 190.8 ng/ml, 22.68 +/- 7.07 nmol/min per ml, 6.62 +/- 2.78 ng/ml, and 7.45 +/- 2.99 pg/ml, respectively. There were significant correlations between plasma levels of type II PLA2 and TM (r = 0.767, p < 0.0001), between PAFAH and TM (r = 0.542, p = 0.0076), between type II PLA2 and ET-1 (r = 0.688, p = 0.0003), and between PAFAH and ET-1 (r = 0.516, p = 0.0117). These results suggest that the increases in plasma type II PLA2 and PAFAH are related to vascular endothelial disorders in patients with infected burns.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

[The inhibitory effects of ulinastatin on the increase of interleukin 8 and 6 during open heart surgery].

The effects of ulinastatin on the serum interleukin 8 and 6 (IL-8, 6), granulocyte elastase (GEL), creatinphosphokinase (CK) and CK-MB were studied during open heart surgery under cardiopulmonary bypass (CPB). Eleven patients (group I) did not receive ulinastatin. Thirteen patients (group II) received 600,000 units of ulinastatin intravenously before CPB and before declamping of aorta and 12 patients (group III) received 300,000 units more added in the priming solution. The serum concentration of IL-8 and 6 increased at 60, 120, 180 min. after reperfusion compared with the preoperative value in the three groups. But, at each time point after reperfusion, IL-8 and 6 levels in group II and III were significantly lower (P < 0.01) than those in group I. GEL increased progressively after reperfusion in the three groups. There was no significant difference in the three groups with CK-MB as well CK release. These results suggest that ulinastatin is useful for protection of reperfusion injury after myocardial ischemia since ulinastatin suppresses production of IL-8 and 6.

Aged↗

Relationship between leukotriene B4 and prostaglandin I2 in patients with sepsis.

To examine the roles of leukotriene B4 (LTB4) and prostaglandin I2 (PGI2), the metabolites of arachidonic acid found in patients with sepsis, we measured the serum levels of LTB4 and a stable metabolite of PGI2, 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), in 22 patients with sepsis. Results were analyzed in relation to patients' survival. The serum levels of both LTB4 and 6-keto-PGF1 alpha were significantly higher in patients who died than in those who survived, thus serving as indicators of illness severity. There was a significant correlation between LTB4 and 6-keto-PGF1 alpha levels. The present study suggests that LTB4, a potent leukocyte activator, induces damage to vascular endothelial cells in patients with sepsis, resulting in the excessive production of PGI2 and, consequently, serious illness.

6-Ketoprostaglandin F1 alpha↗

[Limulus test (factor G pathway) positive substance during cardiopulmonary bypass].

Limulus cascade reaction is found to be frequently activated by the plasma in the patients undergoing cardiopulmonary bypass (CPB). Recently, it is considered that this phenomenon occurs by factor G pathway reactive activity (GPRA) rather than endotoxin that activates factor C pathway. In the present report, we investigated circulating endotoxin and GPRA in 32 patients undergoing CPB. Plasma was pretreated by the New PCA method, and assay was performed by two limulus tests; Toxicolor (reactive with endotoxin and GPRA) and Endospecy (endotoxin-specific). Thirty-two patients were classified into four groups by clinical diagnosis, Group A; dissecting aneurysm of the aorta (6 patients), Group B; ischemic heart disease (9 patients), Group C; heart valve disease (8 patients), Group D; congenital heart disease and myxoma in left atrium (9 patients). GPRA in Ringer's lactate hardly increased during previous circulation before operation. The highest plasma GPRA concentration in all patients was observed at the end of CPB, 415 +/- 342pg/ml, but plasma endotoxin concentration was within normal range. At the end of CPB, plasma GPRA concentrations were 761 +/- 180pg/ml in Group A, 646 +/- 341pg/ml in Group B, 230 +/- 86pg/ml in Group C, and 113 +/- 65pg/ml in Group D. GPRA increase ratio (GPRA increase value/CPB time) of Groups A and B was significantly higher (p < 0.05) than that of Groups C and D. It was suggested that the origin of plasma GPRA during CPB was not the CPB circuit but the tissue of the patients.

Adolescent↗

Clinical and immunohistochemical studies on TSH-secreting pituitary adenoma: its multihormonality and expression of Pit-1.

Eight patients with thyrotropin (TSH)-secreting pituitary adenoma are described. Serum TSH levels were inappropriately elevated in spite of elevated thyroid hormones. The serum-free glycoprotein alpha-subunit level was elevated in all the patients. The alpha-subunit to TSH molar ratio, a "tumor marker" for TSH-secreting adenoma, ranged from 1.06 to 6.16. All patients had macroadenoma and underwent transsphenoidal surgery. Light-microscopic indirect immunoperoxidase method applied on formalin-fixed paraffin-embedded specimens revealed alpha-subunit and TSH beta immunoreactivity in all adenomas. The proportion of TSH beta-positive cells ranged from 20% to 75% of adenoma cells. Six adenomas (75%) were associated with growth hormone (GH) and/or prolactine (PRL) immunoreactivity. By the double staining method, TSH beta and the alpha-subunit were frequently colocalized in the same cells, but some cells were found to contain either alpha-subunit or TSH beta. We also analyzed the localization of a pituitary-specific transcriptional factor, Pit-1, which has been suggested to play a role in functional differentiation toward growth hormone, prolactine, and TSH. All cases were positive for Pit-1 product using antibody against human Pit-1 synthesized peptide. Pit-1 product was localized in the nuclei of many adenoma cells and was frequently identified in cells that were positive for both TSH beta and growth hormone or prolactine. From our investigations, the role of Pit-1 in multidirectional differentiation during the development of TSH-secreting adenoma was suggested.

Adenoma↗

Plasma levels of TNF-alpha, endothelin-1 and thrombomodulin in patients with sepsis.

To investigate the roles of tumor necrosis factor-alpha (TNF-alpha), endothelin-1 (ET-1) and thrombomodulin (TM) in the plasma of patients with sepsis, plasma levels of endotoxin (Et), TNF-alpha, ET-1 and TM were determined in 30 such patients. Plasma levels of Et, TNF-alpha, ET-1 and TM at the time sepsis was diagnosed were 4.0 +/- 6.7 pg/ml, 98.5 +/- 92.1 pg/ml, 7.0 +/- 4.1 pg/ml and 7.8 +/- 3.3 ng/ml, respectively. There was no significant difference in the plasma Et level between the group of patients that survived (n = 13) or died (n = 17). Plasma levels of TNF-alpha, Et-1 and TM were significantly higher in the group that died than in the surviving group (TNF-alpha, p < 0.0001; ET-1, p = 0.028; TM, p = 0.0004). There were significant correlations between the plasma levels of TNF-alpha and ET-1, of TNF-alpha and TM, and of ET-1 and TM (r = 0.37, p < 0.046; r = 0.61, p = 0.0008; r = 0.63, p = 0.004), respectively. Results suggest that TNF-alpha is involved in the production of ET-1 and TM. Both of those substances appear to be involved in the morbidity of sepsis, and their plasma levels reflect its severity.

Adult↗

Relationships between plasma levels of type-II phospholipase A2, PAF-acetylhydrolase, leukotriene B4, complements, endothelin-1, and thrombomodulin in patients with sepsis.

We determined the plasma levels of type-II phospholipase A2 (type II PLA2), platelet-activating factor acetylhydrolase (PAFAH) leukotriene B4 (LTB4) and of several complements (C3a, C4a, and C5a), which are considered to be among the cytokines and eicosanoids involved in vascular endothelial disorders and that vary in concentration during sepsis. We investigated the relationship between those levels and those of ET-1 and TM levels in plasma. Plasma levels of type II PLA2, PAFAH, LTB4, C3a, C4a, ET-1, and TM at the time that sepsis was diagnosed in 30 patients were 218.3 +/- 179.9 ng/ml, 23.92 +/- 9.66 nmol/min/ml, 90.35 +/- 31.49 pg/ml, 838.73 +/- 2.30 pg/ml, 1951.46 +/- 1697.78 pg/ml, 6.98 +/- 4.08 pg/ml and 7.80 +/- 3.34 ng/ml, respectively. The C5a plasma level was below the limit of detection in all cases. There were significant correlations between type II PLA2 and ET-1 plasma levels (r = 0.39, p = 0.032) and C3a and ET-1 plasma levels (r = 0.60, p = 0.03). There were also significant correlations between type II PLA2 and TM levels in plasma (r = 0.76, p = 0.0017), PAFAH and TM plasma levels (r = 0.53, p = 0.037), LTB4 and TM plasma levels (r = 0.46, p = 0.016) and C4a and TM plasma levels (r = 0.58, p = 0.037). Results suggest that the elevation of type II PLA2, PAFAH, LTB4 and complement in plasma is involved in vascular endothelial disorders in patients with sepsis.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

PAF acetylhydrolase and arachidonic acid metabolite levels in patients with sepsis.

To examine the relationship between arachidonic acid metabolism and sepsis, we determined the blood concentration of platelet-activating factor acetylhydrolase (PAFAH) and of arachidonic acid cascade substances, leukotriene B4 (LTB4), thromboxane B2 (TXB2), and 6-keto-prostaglandin Fla (PGF1a), in patients with clinical sepsis. Blood concentrations of PAFAH, LTB4, TXB2 and PGF1a at the time of the initial diagnosis of sepsis were 23.9 +/- 9.7 nmol/min/mL, 90.4 +/- 31.5 pg/mL, 55.3 +/- 44.1 pg/mL and 22.3 +/- 11.9 pg/mL, respectively. There was a significant correlation between the blood PAFAH and LTB4 concentration (r = 0.520, p = 0.0033) and the diagnosis of sepsis. There also was a significant correlation between the blood PAFAH and TXB2 concentration (r = 0.460, p = 0.0311). There was no correlation between the blood PAFAH and PGF1a concentrations. Elevated LTB4 and TXB2 concentrations showed a significant correlation with the PAFAH concentration in patients with sepsis, suggesting a direct relationship between these substances.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Blood cytokine and complement levels in patients with sepsis.

We measured serum levels of endotoxin, cytokines, and eicosanoids and investigated their relationship to serum complement levels in patients with sepsis. Serum endotoxin (Et) levels (5.3 +/- 2.4 pg/ml) were within the normal range, but levels of tumor necrosis factor-alpha (TNF-alpha, 114 +/- 104.94 pg/ml), interleukin 6 (IL-6, 86.7 +/- 50.9 pg/ml), interleukin 8 (IL-8, 86.8 +/- 49.7 pg/ml), type-II phospholipase A2 (type II PLA2, 211.3 +/- 193.9 ng/ml), leukotriene B4 (LTB4, 88.7 +/- 27.2 pg/ml), thromboxane B2 (TXB2, 58.7 +/- 50.9 pg/ml) and 6-keto-prostaglandin F1 alpha (PGF1 alpha, 21.0 +/- 11.0 pg/ml) levels were above normal. Levels of C3a (1088.4 +/- 83.8.7 ng/ml) and C4a (1951.5 +/- 1697.8 ng/ml) were also above normal; C3 (66.0 +/- 25.6 mg/dl) and C4 (23.6 +/- 5.3 mg/dl) were within the normal range, and C5a was lower than the detectable limit in all but one of the subjects. Serum TNF-alpha was significantly correlated with C3a (p < 0.001). Serum IL-6 had a significant negative correlation with C3 (p = 0.002) and C4 (p = 0.010). Type II PLA2 was significantly correlated with C3a (p < 0.001). There were no significant correlations between serum Et or IL-8 and serum C3, C4, C3a or C4a. Our findings suggest that increased levels of TNF-alpha, IL-6, and Type II PLA/ in patients with sepsis contribute to activation of the complement system.

Adult↗

Polyclonal B cell activation, endotoxin tolerance, and limulus tests of endotoxin preparations of some periodontopathogens.

Potencies of polyclonal B-cell activation in C3H/HeN mice of Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum, and Porphyromonas gingivalis endotoxins were 0.36, 0.13 and 0.04, taking Salmonella abortusequi as 1.0. F. nucleatum and P. gingivalis endotoxins showed positive reactions in C3H/HeJ mice. Most activities in C3H/HeN other than that of F. nucleatum were suppressed by polymyxin B. In C3H/HeJ mice, similar inhibitions were only 60% for P. gingivalis and hardly observed with F. nucleatum. The resistances to polymyxin B could be due to protein in the endotoxins. A promoting effect of T cells added to B cells was observed only in the activity of F. nucleatum endotoxin in C3H/HeJ mice; there was no influence in other groups. Test endotoxins had nearly the same ability to produce colony stimulating factor as did references and could not produce the factor in tolerant mice. The clinical significance of tolerance is discussed. Regression lines of endotoxin doses and limulus activities of test endotoxins and Salmonella were parallel, either in specific or non-specific tests. The lines of two test groups were also parallel; values obtained by two tests were very close. These data indicate that the test endotoxins did not contain (1-3)-beta-D-glucan and elicited qualitatively similar limulus reactions to that of the reference, despite their different chemical natures. In conclusion, these test preparations had an endotoxicity similar to that of the reference and contribute to produce periodontitis through polyclonal B cell activation.

Aggregatibacter actinomycetemcomitans↗

Platelet-activating factor (PAF) acetylhydrolase activity, type II phospholipase A2, and cytokine levels in patients with sepsis.

Platelet activating factor acetylhydrolase (PAF-AH) activity was measured in patients with sepsis, and its relationships with various cytokines and endotoxin were evaluated. PAF-AH activity was significantly higher (p = 0.0136) in 17 patients who died than 13 patients who survived. PAF-AH activity showed significant correlations with the plasma endotoxin, TNF-alpha, and IL-8 levels. These findings suggest that PAF-AH activity reflects the severity of the pathological condition.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Relationship between thromboxane B2 and 6-keto-prostaglandin F1 alpha in sepsis.

To examine the roles of thromboxane A2 and prostaglandin I2, which are arachidonic acid metabolites found in patients with sepsis, we measured the serum levels of their respective stable metabolites, thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) in 22 patients with sepsis. Results were analyzed in relation to patients' survival. The levels of both TXB2 and 6-keto-PGF1 alpha were significantly higher in patients who died than in those who survived, thus reflecting the severity of the patients' illness. There was a significant correlation between the levels of TXB2 and 6-keto-PGF1 alpha. These findings suggest that TXA2 and PGI2 are chemical mediators involved in the severity of clinical sepsis.

6-Ketoprostaglandin F1 alpha↗

Serum complement levels and severity of sepsis.

The activities (C3a, C4a, C5a) and concentrations (CH50, C3, C4, C5) of serum complement were measured to evaluate the involvement of complement in sepsis. We studied 27 patients with sepsis who were divided into the survivors (Group 1) and the nonsurvivors (Group 2). The levels of C3a, C4a, and C5a were all significantly higher in Group 2 than in Group 1 and closely reflected the severity of sepsis. Levels of C3 and C4 were significantly lower in Group 2 than in Group 1, presumably because these components were consumed as a result of activation of both the alternative and classical pathways. The levels of CH50 and C5 did not differ significantly between the two groups. These findings suggest that complement is closely involved in the exacerbation of the condition of septic patients, and that the measurement of complement activity is useful for evaluating the severity of sepsis.

Adult↗

Significance of alpha-tocopherol and interleukin 8 in septic adult respiratory distress syndrome.

To elucidate the relationship between active oxygen and interleukin 8 (IL-8) in patients with septic adult respiratory distress syndrome (ARDS), we determined the serum levels of alpha-tocopherol, which has an antioxidant action, and IL-8 in seven patients with this disease. Serum alpha-tocopherol and IL-8 levels determined at the time of diagnosis of septic ARDS were 0.97 +/- 0.36 mg/dl and 0.98 +/- 0.99 ng/ml, respectively. A significant correlation was found between serum alpha-tocopherol level and IL-8 level (r = -0.758, p = 0.0473). These findings suggest that IL-8 activates neutrophils, which produce active oxygen.

Adolescent↗

[A case of primitive neuroectodermal tumor in the chest wall ("Askin's tumor")].

We report a case of Askin's tumor, primitive neuroectodermal tumor (PNET) in the chest wall, with review of reported cases of PNET. Our case was the ninth of Askin's tumor and the 36th of PNET in Japan. A 12-year-old girl was hospitalized because of a large right intrathoracic mass. The serum neuron-specific enolase (NSE) was 11.4 ng/ml, slightly increased, and the urinary excretion of catecholamine metabolites was normal. The needle biopsy specimens were diagnosed as small round cell sarcoma. At surgery we found an encapsulated multilobular mass in the region. The chest wall was resected partially to extirpate it completely. Its macroscopic and microscopic features were almost similar to the description of Askin et al. The immunohistochemical staining of the cells was positive for NSE, strongly suggesting the neurogenic origin. After surgery, intensive chemotherapy with autologous bone marrow transplant was performed, and she has been living without sign of recurrence for two years.

Child↗

[Significance of overexpression of p53 protein in human breast cancer].

Overexpression of p53 protein was examined by immunohistochemical assay. In 143 primary breast cancer patients, consisting of 18 patients with family history of breast cancer or past history of breast cancer and 125 patients with no such histories. In the later 125 patients, overexpression of p53 was shown in 42 patients (33.6%), however in the former 18 patients, p53 overexpression was found in 15 (83.3%). It was suggested that p53 protein is frequently overexpressed in patients with high risks like history of breast cancer and family history of breast. On the other hand, regarding the value of p53 overexpression as a prognostic indicator, an univariate analysis demonstrated that the relapse free survival of patients with over 50% p53 positive all rate was significantly worse compared to that of patients with less than 50% p53 positive all rate (p < 0.05). However multivariate analysis did not demonstrate the significant value (p < 0.1), suggesting that overexpression of p53 is marginal as a prognostic indicator.

Breast Neoplasms↗

Relationship between cytokines and leukotriene B4 in sepsis.

To clarify the relationship between cytokines and arachidonic acid metabolites, we measured tumor necrosis factor (TNF-alpha), interleukin 8 (IL-8), and leukotriene B4 (LTB4). The subjects consisted of 30 patients with sepsis. The results were compared between patients who died (Group A) and those who survived (Group B). All TNF-alpha, IL-8, and LTB4 levels were significantly higher in Group A than in Group B, reflecting the severity of the disease. The LTB4 levels were significantly correlated with the TNF-alpha level and the IL-8 level. These results suggest that inflammatory cytokines, excessively produced due to inflammatory reactions, stimulate as a mediator the release of arachidonic acid, increasing LTB4 production.

Adult↗

Clinical effects of intramuscular administration of a small dose of polymyxin B to patients with endotoxemia.

The effects of intramuscular injections of minute amounts of polymyxin B were studied in 42 patients with endotoxemia. Plasma endotoxin was measured by means of an endotoxin-specific Endospecy test (Seikagaku Corp., Tokyo, Japan) after pretreatment of the plasma with a new perchloric acid method that we developed. The normal value of plasma endotoxin is less than 9.8 pg/mL. Polymyxin B was administered at a dose of 12,500 U every 6 hours. Plasma endotoxin rapidly decreased to the normal range in 40 of the 42 patients. Body temperature fell significantly. APACHE II scores were also significantly improved. Tumor necrosis factor-alpha and interleukin-6 (IL-6) decreased in survivors, while tending to persist in high values in patients who died. No side effects were observed in any of the patients. In conclusion, intramuscular injections of small doses of polymyxin B were useful in the treatment of endotoxemia.

Adolescent↗