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Biomedical subjects

K Setoguchi

Publications and source records attributed to K Setoguchi.

32 records · Page 2Linked to original sources

Pathogenesis of influenza virus-induced pneumonia: involvement of both nitric oxide and oxygen radicals.

The role of nitric oxide (NO) in the pathogenesis of influenza virus-induced pneumonia in mice was investigated. Experimental influenza virus pneumonia was produced with influenza virus A/Kumamoto/Y5/67(H2N2). Both the enzyme activity of NO synthase (NOS) and mRNA expression of the inducible NOS were greatly increased in the mouse lungs; increases were mediated by interferon gamma. Excessive production of NO in the virus-infected lung was studied further by using electron spin resonance (ESR) spectroscopy. In vivo spin trapping with dithiocarbamate-iron complexes indicated that a significant amount of NO was generated in the virus-infected lung. Furthermore, an NO-hemoglobin ESR signal appeared in the virus-infected lung, and formation of NO-hemoglobin was significantly increased by treatment with superoxide dismutase and was inhibited by N(omega)-monomethyl-L-arginine (L-NMMA) administration. Immunohistochemistry with a specific anti-nitrotyrosine antibody showed intense staining of alveolar phagocytic cells such as macrophages and neutrophils and of intraalveolar exudate in the virus-infected lung. These results strongly suggest formation of peroxynitrite in the lung through the reaction of NO with O2-, which is generated by alveolar phagocytic cells and xanthine oxidase. In addition, administration of L-NMMA resulted in significant improvement in the survival rate of virus-infected mice without appreciable suppression of their antiviral defenses. On the basis of these data, we conclude that NO together with O2- which forms more reactive peroxynitrite may be the most important pathogenic factors in influenza virus-induced pneumonia in mice.

Animals↗

Expression of inducible nitric oxide synthase and its involvement in pulmonary granulomatous inflammation in rats.

Two types of pulmonary granulomatosis were produced in rats by intratracheal instillation of zymosan or silica. In both models, immunostaining with anti-rat monoclonal antibody for inducible nitric oxide synthase (iNOS), ANOS11, showed that the intensity of iNOS immunoreactivity in the inflammatory lesions peaked at 3 days and declined thereafter. Immunohistochemical double staining and in situ hybridization demonstrated the expression of iNOS in neutrophils, monocyte-derived macrophages, and bronchiolar epithelial cells in the pulmonary lesions. Electron spin resonance spectroscopy revealed the production of an excessive amount of nitric oxide (NO) in the pulmonary lesions. Immunostaining with a polyclonal antibody against nitrotyrosine indicated the formation of nitrotyrosine residues in the granulomatous lesions, particularly in the periphery of the lesions, providing indirect evidence for the generation of peroxynitrite anion in the zymosan- or silica-instilled lungs. Administration of N omega-nitro-L-arginine methyl ester or S-methylisothiourea sulfate, which significantly suppressed NO production, resulted in marked reduction of monocyte/macrophage infiltration as well as in inhibition of induction of monocyte chemoattractant protein-1 in the lesions. These data indicate that NO and its more reactive product peroxynitrite anion may be important mediators of granuloma formation in the lung.

Animals↗

[Clinical experience of extracorporeal life support with the use of centrifugal pump ECMO].

Many reports have documented the good results with the use of extracorporeal life support in severe respiratory and circulatory failure. In our institution, we have used the centrifugal pump (Bioconsol 540: Biomedicus Co. Ltd.) ECMO for extracorporeal life support, and obtained good results in three cases. We used V-V bypass ECMO in one case (idiopathic interstitial pneumonia) and V-A by-pass ECMO in other two cases (ARDS and meconium aspiration syndrome). Duration of total bypass in three cases were 34, 51 and 140 hours, respectively. Recent reports on the use of centrifugal pump have indicated that it can bring excellent results of circulatory assist for cardiogenic shock. Compared to the roller pump method, the use of centrifugal pump ECMO was very simple, and could serve as an effective method for providing improvement in a relatively short period.

Adult↗

[Interleukin-6 and glucocorticosteroid responses to cardiopulmonary bypass].

The responses of interleukin-6 (IL-6), ACTH, cortisol, WBC, CRP to cardiopulmonary bypass (CPB) were studied in 5 patients who underwent elective CABG (N = 4) and AVR (N = 1). IL-6 started to increase from 3 h after the beginning of the operation at which aortic clamp was removed and reached a peak after 4 h at which CPB was withdrawn. ACTH also reached a peak after 4 h. The increase of cortisol started from 2 h when aorta was clamped, which was earlier than that of IL-6. IL-6 and ACTH fell sharply to pre-CPB levels before first postoperative day (1 POD) while cortisol remained high postoperatively. CRP level and WBC counts were maximum at 2 POD. The results suggest that the cortisol response to CPB is not only caused by IL-6, but also by other factors, such as IL-1 and TNF.

Adrenocorticotropic Hormone↗

[Cortisol responses to rapid ACTH test in patients with multiple organ failure].

Cortisol concentrations are usually elevated in sepsis, during major surgery and in burns. Adrenocortical response to stress seems to be essential for survival. To investigate the endogenous adrenocortical response to multiple organ failure, rapid ACTH stimulation tests were used in 15 patients. Patients were divided to nonsurvival group and survival group. Patients in both groups appeared to have increased adrenocortical activity, because basal cortisol concentrations were above normal (non-survival group: 33.8 +/- 13.7 micrograms.dl-1, survival group: 19.1 +/- 3.8). There are no significant differences between the two groups. We could not find absolutely adrenal insufficient patient. Plasma cortisol concentrations increased significantly in patients of both groups following ACTH stimulation. We found poor response to ACTH in two patients in non-survival group with very high basal cortisol concentrations. But there is no significant difference of cortisol response between the two groups. We could not determine whether the high mortality is associated with poor response to ACTH or not.

Adrenal Cortex↗

[Evaluation of blood purification in perioperative acute renal failure].

The technical aspects of blood purification have made a great progress during 1980's. We reviewed our experiences of blood purification for the past six years. Between 1986 to 1991, we treated 48 perioperative patients with acute renal failure (ARF). Four were intraoperative cases and 46 were postoperative cases. Three of four intraoperative patients received major cardiovascular surgery, and hemodialysis was connected directly to ECC in these three cases, and in other one case, ARF was treated with continuous hemofiltration (CHF). There was no intraoperative complication. One patient died of septic multiple organ failure (MOF), but other three patients were discharged uneventfully. Thirty five postoperative ARF patients showed oliguric ARF, and their major causes were LOS (65%) and septic shock (29%). We treated these ARF patients with CHF combined with HD (63%), CHF only (28%) and HD only (9%). There were 21 deaths (60%) in this group and most common cause of death was septic MOF. Eleven postoperative ARF patients showed non-oliguric renal failure, and major cause of this type of ARF was thought to be aortic dissection and relative hypotension (45%). We treated these non-oliguric ARF patient with HD only (73%) and HD combined with CHF (27%). One of these non-oliguric ARF patients died from ARDS.

Acute Kidney Injury↗

[Hemodynamic management of LOS using prolonged VA bypass circulatory assist].

The authors managed five LOS patients using prolonged V-A bypass circulatory assist. Maximum CVP values were under 12 mmHg in three survivors, and 17 mmHg and 20 mmHg in two nonsurvivors. Maximum PCWP values were under 14 mmHg in survivors, and 19 mmHg and 20 mmHg in nonsurvivors. Dopamine was administrated in all cases and norepinephrine was administrated at a rate of less than 0.3 microgram.kg-1.min-1 in survivors, and in two nonsurvivors, norepinephrine was used at a rate of 0.36 and 1.2 micrograms.kg-1.min-1. Before and after disconnection of V-A bypass, the bypass flow of the three survivors were under 1.0 l.min-1 just before disconnection, and immediately after it, the preload did not increase, and the dose of administrated catecholamine increased. V-A bypass time intervals of the three survivors were 71, 42 and 87 hours, and those of the two nonsurvivors were 71 and 43 hours. Maximum bypass flow rate was above 40ml.kg-1.min-1 in four of five patients. The authors discussed the management of the patients' heart and of the V-A bypass machine during the prolonged V-A bypass circulatory assist.

Aged↗

[Diuretic effects of aminophylline in patients after cardiac surgery].

Diuretic effects of aminophylline in patients after cardiac surgery were studied by using the local renal thermodilution catheter (Goodman Co. Ltd.). The subjects were 11 patients who underwent cardiac surgery in our hospital. All patients had shown almost normal renal and endocrine function. On the day of operation, we indwelld renal thermodilution catheter into the left renal vein under fluoroscopy. After operation, when the urinary volume decreased below 1 ml.kg-1.hr-1, we administered aminophylline at a rate of 2 ml.kg-1.hr-1. We measured HR, BP, CO, PAP, CVP, renal blood flow, urinary volume, urinary electrolytes, plasma renin activity, angiotensin II, aldosteron, ADH and alpha hANP just before and after infusion of aminophylline. The urine volume, renal blood flow and renal blood flow distribution rate showed significant increases of about 70%, 40% and 35% respectively. But hemodynamic parameters including HR, mean BP and CO increased for 5%, 10% and 8% respectively after administration of aminophylline. In the endocrine system, only angiotensin II increased significantly but aminophylline did not cause any change in endocrine system. The results suggest that diuretic effect of aminophylline is mainly achieved by increasing renal blood flow.

Adult↗

An automated optoelectronic reticulocyte counter.

Microscopic reticulocyte counting is time consuming and imprecise. A new reticulocyte counter has been developed, and the authors evaluated its utility for laboratory use. The counter, R-1000 of Sysmex-TOA Medical Electronics Company, Kobe, Japan, is based on the principles of flow cytometry. Reticulocytes are detected as fluorescent cells stained with a basic dye, auramine O, under argon-laser light. The automated count had high correlation to the manual count (r = 0.941). Linearity and reproducibility were both high. About 60 specimens were tested in one hour. Not only the reticulocyte percentage and count but also the maturity of reticulocytes was found from the intensity of the fluorescence, whether high, moderate, or slight. Normal reference values were 0.007 +/- 0.0055 (0.70 +/- 0.55%) for the reticulocytes, (4.63 +/- 1.09) X 10(9)/L for the reticulocyte count, 2.3 +/- 1.9% for highly fluorescent cells, 18.7 +/- 5.1% for moderately fluorescent cells, and 78.8 +/- 6.6% for cells with slight fluorescence. In patients with suppressed bone marrow function, such as is caused by chemotherapy, the reticulocyte fraction and count were low, and cells with slight fluorescence increased. In patients in whom bone marrow function was stimulated, such as with hemolytic anemia, the reticulocyte percentage, reticulocyte count, and highly fluorescent cells were high. Patients with chronic renal failure being treated by hemodialysis had a similar reticulocyte pattern to that in hemolytic anemia except that the reticulocyte count was decreased. Results for elderly patients were not different from those of healthy young controls. Some patients with a normal reticulocyte count and percentage had numerous highly fluorescent cells, perhaps because of hemolytic anemia not yet identified. Automated reticulocyte counting provides reliable data, so such measurement should be useful for analysis of the kinetics of red blood cells and for the study of the pathogenesis of anemia.

Adult↗

An automated reticulocyte counting method: preliminary observations.

We evaluated the counting of reticulocytes in the peripheral blood with a newly developed flow cytometer type of automated counter that performs a single test within 60 s. The volume of sample needed is 100 microliters and the cells are stained with auramine-O in the counter. The mean within-run reproducibility was 4.66% (CV, n = 50), and dilution of blood gave highly linear results with an r value of 0.996. Correlation was good between manual reticulocyte counts and those performed with the counter (r = 0.893). Samples with large numbers of leucocytes, erythrocytes, or platelets did not interfere with the automated reticulocyte counting, and provided accurate and precise data.

Autoanalysis↗

Utilization and requirement of dietary protein taking into account the dermal and miscellaneous nitrogen losses in Japanese women.

Utilization and requirement of mixed protein in the conventional Japanese diet and the obligatory integumental and miscellaneous nitrogen losses were measured in female subjects. Twelve female students aged 18 to 24 years were given conventional low-protein diets at N intake levels of 50, 70, and 90 mg/kg/day for 10 days. Constituents of the diets corresponded to those of average intake of the Japanese in recent years (1982). N balances were estimated and regression equations between N intake (X) and N balance (Y) were calculated by the multiple level-constant variation method. The equation was Y = 0.426X - 40.0 (n = 36, r = 0.615, p less than 0.01) and the intersection of the regression line with zero nitrogen balance was 93.9 +/- 14.3 mg N/kg/day. The mean digestibility was 92.2 +/- 4.7%. In another experimental group, nitrogen losses due to hair, nails, and menstruation in ten Japanese women were 0.624 +/- 0.172, 0.020 +/- 0.005, and 1.76 +/- 0.68 mg/kg/day, respectively. In a third experimental group, mean of the integumental N losses was 2.8 mg/kg/day in both the subjects given a low-protein diet (19 women) and an ordinary-protein diet (4 women). It increased to 12.7 mg N/kg/day when subjects exercised in summer (4 subjects). The protein requirement in the conventional Japanese diet estimated as the sum of the mean requirement of dietary protein and obligatory dermal and miscellaneous nitrogen losses in Japanese women was 99.1 mg N/kg/day or 0.62 g protein/kg/day. The net protein utilization (NPU) of the proteins at the N intake level for N equilibrium was estimated as 48.

Adolescent↗