Training effects on concentrations of immunoreactive superoxide dismutase iso-enzymes in human plasma.
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Biomedical subjects
Publications and source records attributed to N Taniguchi.
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In the present study, a whole-blood culture was employed to examine the ability of preterm and term newborn infants to produce interleukin-6 (IL-6) in response to major bacterial pathogens such as group B streptococci, Escherichia coli, Listeria monocytogenes, and Streptococcus pneumoniae. Similarly, in response to stimulation with lipopolysaccharide, a potent stimulant for monocyte cytokine production, appreciable levels of IL-6 activity in the stimulated whole blood from term newborns as well as adults was effectively induced by all of these pathogens. In contrast to that of term infants, the bacteria-induced IL-6 production of preterm infants, especially those born before 30 weeks of gestation, was somewhat decreased (P less than 0.01 for each pathogen). It was also demonstrated that IL-6 responses to lipopolysaccharide stimulation were reduced in preterm newborns (for term versus preterm newborns less than 30 weeks of gestation, P was less than 0.01). These findings imply some inherent abnormality of monocytes in preterm babies. The diminished IL-6 production may be partly responsible for the susceptibility of preterm newborn infants to bacterial infections.
The distribution of rat manganese superoxide dismutase (Mn-SOD) was immunohistochemically investigated in the rat stomach with a specific polyclonal antibody and a labeled streptavidin-biotin immunoglobulin detection system in cryosections. Parietal cells in the stomach were intensely stained, whereas the other epithelial cells in the gastric gland and pit exhibited only slight staining. Rapid-freezing and freeze-substitution immunoelectron microscopy revealed that Mn-SOD in parietal cells was mainly localized in mitochondria. Therefore, the large amount of Mn-SOD in parietal cells is due to the abundant mitochondria, in which Mn-SOD is considered to play important roles in protecting the ion pump and the cell itself from superoxide insult. Application of Triton X-100, cryosectioning, and the streptavidin-biotin system are needed to distinctly visualize Mn-SOD with our antibody. Treatment of the cryosections with Triton X-100 enhanced not only the immunoreactivity but also the false-positive staining, which showed a similar distribution pattern to that of Mn-SOD and thus made it difficult to determine the localization. The most plausible cause of the false-positive staining is thought to be endogenous biotin in the stomach, which survives paraformaldehyde fixation and is revealed by Triton X-100 treatment. Suppression of the endogenous streptavidin binding activity is important when cryosections, the streptavidin-biotin system, and Triton X-100 are employed.
Our previous study indicated that erythrocyte Cu,Zn-superoxide dismutase (Cu,Zn-SOD) undergoes glycation and inactivation in vivo (1) and in vitro (2). The aim of the present study was to assess glycated Cu,Zn-SOD in patients with insulin-dependent diabetes mellitus. Glycated Cu,Zn-SOD, which binds to a boronic acid affinity column, was measured by the enzyme-linked immunosorbent assay. The percentage of the glycated form in 25 insulin-dependent diabetic children was 40.2 +/- 8.2%; this was significantly higher than that in the normal controls (P less than 0.01). The specific activity of the glycated form in the diabetic children was 163,000 +/- 33,000 IU/mg Cu,Zn-SOD protein, significantly lower than that in controls (P less than 0.01). These data indicate that glycated and less active Cu,Zn-SOD is increased in erythrocytes of patients with insulin-dependent diabetes mellitus.
Effects of cycle ergometer exercise (approximately 75% VO2max for 15 min) on the concentrations of immunoreactive Mn- and CuZn-superoxide dismutases (SOD) in plasma were studied on 10 male students. During the experimental period, Mn-SOD concentration did not vary substantially. On the other hand, CuZn-SOD concentration decreased markedly at 15 min and 24 hr after the exercise; that is, CuZn-SOD appeared to differ virtually from Mn-SOD in recovery pattern.
Human liver manganese superoxide dismutase (Mn-SOD) was highly purified by a simple procedure and crystallized. A monoclonal antibody against Mn-SOD, whose antigen-binding epitope is a C-terminus peptide was developed. Using this antibody, an enzyme-linked immunosorbent assay (ELISA) was developed. We found that Mn-SOD is highly expressed in human ovarian cancer and the serum level of the enzyme is a useful marker for the diagnosis and monitoring of the epithelial type of ovarian cancer. Tumor necrosis factor-alpha (TNF), lipopolysaccharide, IL-1 and phorbol ester induced the m-RNA of Mn-SOD as well as protein levels in TNF-resistant cells. No such induction was observed in Cu, Zn-SOD. Studies on the induction mechanisms indicated that at least two separate signal-transducing pathways are involved in expression of the Mn-SOD gene. One is triggered by protein kinase C activation itself in the absence of new protein synthesis. The other can be activated by stimulations with various cytokines in which a protein factor that can be induced by phorbol ester treatments is involved.
Serum Mn-superoxide dismutase (Mn-SOD) levels were determined in patients with acute myocardial infarction by an enzyme-linked immunosorbent assay (ELISA). The serial determinations performed on 29 patients with acute myocardial infarction indicated that Mn-SOD appears in serum in a biphasic manner; an early small elevation was observed at approximately 16.2 (+/- 7.3) h and a high elevation at approximately 108 (+/- 20.6) h after the onset of symptoms. A negative correlation was found between the maximum value of the late elevation of Mn-SOD and left ventricular function. Plasma levels of tumor necrosis factor-alpha (TNF-alpha) were also elevated in acute myocardial infarction. These facts suggest that TNF-alpha secretion from the infarcted area resulted in the production of Mn-SOD and that the induced Mn-SOD was released from myocytes into serum through damaged membranes, resulting in the late elevation.
Metabolic fates of nicotinamide in Wistar and LEC rats were compared. In Wistar rats (normal rats) nicotinamide was generally catabolized to N1-methyl-4-pyridone-3-carboxamide (4-Py) through N1-methylnicotinamide (MNA). But in LEC rats nicotinamide catabolism mainly stopped at MNA. Therefore, the excretion ratio of (N1-methyl-2-pyridone-5-carboxamide + 4-Py)/MNA, which is an index of amino acid adequacy, was much lower in the LEC rats than in the Wistar rats. This phenomenon was attributed to the fact that the 4-Py-forming MNA oxidase activity was much lower in the LEC rats than in the Wistar rats. The NAD contents in liver and blood were also lower in LEC rats than in Wistar rats. These results suggest that the ability to synthesize proteins such as 4-Py-forming MNA oxidase and dehydrogenases may be impaired in LEC rats.
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In view of the controversy with respect to the interaction of jacalin with human IgA2, a study was undertaken to assess the reactivity of the Artocarpus heterophyllus lectin, as well as the lectin from Artocarpus integer (lectin C), with subclasses of human immunoglobulin A by ELISA. Our data is consistent with the view that Artocarpus lectins have no affinity for the IgA2 immunoglobulins. In further support of the findings, we have established that N-linked oligosaccharide moieties of IgA have no significant bearing in the lectin-immunoglobulin binding. Interaction was also not affected in the presence of 1% (w/v) BSA.
Interleukin-6 (IL-6) plays a key role in inflammatory and immune responses in the host. In the present study, the IL-6 activity in urine from patients with various renal diseases was examined to elucidate the pathological and clinical significance of urinary IL-6. In patients with mesangial proliferative glomerulonephritis (mes-PGN) including, IgA nephropathy, the urinary IL-6 activity tended to increase with the progression of mesangial hypercellularity. In four patients with IgA nephropathy, urinary IL-6 activity increased markedly but transiently during episodes of acute exacerbation associated with upper respiratory tract infection. In addition, it was demonstrated that urine from patients with other types of PGN such as poststreptococcal acute glomerulonephritis and membrano-proliferative glomerulonephritis contained large quantities of IL-6. However, the levels of urinary IL-6 activity were almost within the normal range in non-proliferative glomerular diseases such as membranous nephropathy, minimal change nephrotic syndrome and lupus nephritis (WHO class I and V), non-glomerular bleeding and orthostatic proteinuria. It should be noted that a marked increase in urinary IL-6 was often observed in the patients with urinary tract infection. These results indicated that IL-6 in urine might be derived from various types of cells participating in inflammatory reactions not only in the renal parenchyma but also in the urinary tract.
The hypothalamo-pituitary-gonadal axis was studied in 10 young manic-depressive or psychotic women whose symptoms obviously fluctuated in association with the menstrual cycle. The common clinical features of these cases were (1) young female aged between 15 and 25, (2) the symptoms fluctuated obviously in association with the menstrual cycle, and (3) severe manic-depressive, or psychotic symptoms. While, in two cases, the depressive or psychotic phases had repeated many times for several years, the rest eight cases did not have a long psychiatric past history. The common hormonal features among these 10 cases were elevated basal LH (7 of 10 cases), decreased basal FSH (6 of 10), greater response of LH and normal response of FSH to LHRH (8 of 8), lack of or insufficient increase of progesterone in the luteal phase (7 of 8), and elevated serum testosterone (5 of 10), androstenedione (4 of 10) and DHEA-S (3 of 9). These abnormalities resemble those of polycystic ovary syndrome (PCOS). Five of the 10 cases showed mild hirsute signs such as mustache, acne, and/or well-developed musculo-skeletal system. An ultrasonographical study revealed polycystic changes in 7 of 10 cases. Ordinary psychotropic pharmacotherapy was not effective sufficiently and hormonal therapy was tried in these 10 cases. Clomiphene citrate was administered on Day 5-9 of the menstrual cycle at a daily dose of 50mg orally in 9 cases, and it was effective to prevent recurrence of manic episode in one case, and to improve manic-depressive or psychotic symptoms in 6 cases. In these 6 cases, the effects were commonly observed within 1 or 2 weeks subsequent to the administration being completed. Daily dexamethasone administration was effective in one case with high serum DHEA-S level in whom clomiphene citrate worsened the psychotic symptoms, and thyroid hormone was effective in one case. In comparison with the pathophysiology of PCOS, a possible relationship was suggested between psychiatric problems and the PCOS-like hormonal abnormalities in these cases.
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We studied the effect of Cu,Zn-superoxide dismutase (SOD) and Mn-SOD, which are specific scavenging enzymes of the superoxide anion radical, on ovulation and examined the localization of SOD in rat ovaries. The results were as follows. 1) The number of ova in the Cu,Zn-SOD (8 mg x 4) administrated group (27.8 +/- 5.4 : p less than 0.01) was significantly reduced compared to the control group (49.0 +/- 3.3). Similarly, the number of ova in the Mn-SOD (2 mg x 2) administrated group (16.9 +/- 7.6 : p less than 0.01) was significantly reduced compared to the control (52.9 +/- 6.3). 2) In the rat ovary, Cu,Zn-SOD examined by the immunohistological method was found to be localized in the granulosa cells of mature Graafian follicles, growing follicles, primordial follicles and epithelial cells of the fallopian tubes. Mn-SOD was localized in the external theca cells of mature Graafian follicles and the corpus luteum. The activity of SOD estimated by the modified nitroblue tetrazolium method was consistent with the immunohistological localization of both SODs. We considered that oxygen radicals and SODs play an important role in rat ovulation, and Cu,ZN-SOD and Mn-SOD have a different localization and action in the rat ovary.
A monoclonal antibody against manganese superoxide dismutase (Mn-SOD) was assessed for its use in detecting a marker for epithelial ovarian carcinoma. An enzyme-linked immunosorbent assay has been developed to detect serum Mn-SOD. With this assay, only 1.7% of the 240 healthy females tested had more than 130 ng per milliliter of serum Mn-SOD. In contrast, 39 of 66 patients (59.1%) with epithelial ovarian carcinoma showed high levels of Mn-SOD. The serum Mn-SOD increased according to the clinical stage and declined to reflect the effect of therapy. The determination of Mn-SOD levels proved to be a clinical useful marker for monitoring the response to treatment and to early detection of the recurrence of epithelial ovarian carcinomas.
Herein we report case of multilocular cyst of the right kidney complicated with clear cell type renal cell carcinoma. The chief complaint of the 51-year-old male patient was macroscopic hematuria. He underwent radical nephrectomy and was administered postoperative adjuvant chemotherapy with alpha-interferon. No recurrence was found 18 months after operation. Pathogenesis of multilocular cyst of the kidney and the mechanism of malignant transformation are discussed.
The effects of phorbol ester (TPA) and other known stimulators such as tumor necrosis factor (TNF), interleukin-1, and lipopolysaccharide on induction of mRNA for manganese-superoxide dismutase (Mn-SOD) were investigated in various cell lines. TPA enhanced Mn-SOD mRNA expression in TNF-resistant cell lines including HeLa cells, in which the other reagents also induced expression of the gene, but did not affect TNF-sensitive cells, in which the other stimulators did not alter expression of the gene. HeLa cells which had been desensitized to TPA by pretreatment with TPA for 24 h expressed Mn-SOD mRNA at a slightly higher level than the cells without TPA treatment. TPA-pretreated cells stimulated with TNF, however, expressed Mn-SOD mRNA at about twice the level of TNF-stimulated, TPA-untreated cells. When protein synthesis was inhibited by cycloheximide during TPA pretreatment, TNF no more enhanced the Mn-SOD mRNA accumulation. These data suggest that at least two separate signal-transducing pathways are involved in expression of this gene. One is triggered by protein kinase C activation itself in the absence of new protein synthesis. The other can be activated by stimulation with TNF, interleukin-1, or lipopolysaccharide and in which a protein factor that can be induced by TPA treatment is involved.