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Biomedical subjects

N Uchida

Publications and source records attributed to N Uchida.

At least 181 records · Page 10Linked to original sources

Effect of dexamethasone on antioxidant enzymes in fetal rat lungs and kidneys.

To determine if an enhancement in the fetal antioxidant enzyme (AOE) system by maternal dexamethasone (DEX) is specific to organ and dose, the lung and kidney of pups, whose mother received DEX (0.2 or 2 mg/kg) twice, were obtained on days 19 and 20 of gestation. Low-dose DEX increased the four AOE in the day-19 lung, but not in day-20 lung. High-dose DEX decreased the copper-zinc superoxide dismutase (SOD) and glutathione peroxidase in the lungs. Thus, the DEX-induced maturation of lung AOE is dependent on dose and timing. DEX enhanced the four AOE in the day-19 kidney at both doses. In the day-20 kidney, DEX enhanced the manganese SOD at the low dose and also catalase at the high dose, suggesting that DEX accelerates the maturation of kidney AOE as well.

Animals↗

Stem cells.

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Animals↗

Relation between structure and antimicrobial activity of 2-(N,N,N-trialkylammonio)alkyl hydrogen phosphates.

A series of phosphobetaines [2-(N,N,N-trialkylammonio)alkyl hydrogen phosphates], having different alkyl chains and a methylene bridge separating the phosphate and ammonio group, was investigated in order to provide a new antimicrobial agent. Maximal activity was obtained with the compound having a hexadecyl group as a long-chained alkyl group, two methyl groups as short-chained alkyl groups, and a dimethylene bridge as an intercharge distance. In contrast, sodium 2-(N-hexadecyl-N-methylamino)ethyl hydrogen phosphate, 2-(N-hexadecyl-N,N-dimethylammonio)-1-hydroxyethyl iodide, and N-octadecyl-N,N-dimethylammonio acetate showed decreased activity, indicating that the presence of a phosphobetaine moiety was essential for activity. Thus, 2-(N-hexadecyl-N,N-dimethylammonio)ethyl hydrogen phosphate has been found to possess strong antimicrobial activity and a broad antimicrobial spectrum against nine kinds of bacteria (e.g., fungi, yeast, gram-negative and gram-positive bacteria), which are comparable with those of chlorhexidine digluconate.

Anti-Bacterial Agents↗

Effect of diabetes mellitus induced by streptozotocin on renal superoxide dismutases in the rat. A radioimmunoassay and immunohistochemical study.

Two forms of superoxide dismutase, CuZn-SOD and MnSOD, have been investigated in the kidneys of streptozotocin-induced diabetic rats using both radio-immunoassay and immunoenzyme staining. The rats were killed 2, 8 and 12 weeks after the induction of diabetes mellitus and the kidneys excised. Two weeks after the induction of diabetes, the kidneys were hypertrophied because of the proliferation of renal tubular epithelium. However, the total CuZnSOD content of the kidneys did not increase and, because of the epithelial proliferation, the CuZnSOD concentration in each proximal tubular cell was decreased. Armanni-Ebstein lesions were found in the distal tubules 8 and 12 weeks after the induction of diabetes. The cells in these lesions were intensely stained for CuZnSOD, suggesting an adaptive response to the enhanced oxidative stress. The MnSOD staining in the thick ascending limbs of Henle's loops was enhanced in the diabetic kidneys, while that in the cortical tubules was unaltered. MnSOD was assumed to increase in response to hypermetabolism associated with the proliferation of renal tubules. This was most marked in the cells which were rich in mitochondria, again suggesting an adaptive response to enhanced oxidative stress induced by diabetes mellitus. The glomeruli of both the diabetic and control groups were not stained for SODs, and no significant microscopic change was found even 12 weeks after the induction of diabetes mellitus.

Animals↗

Scale and bone type I collagens of carp (Cyprinus carpio).

1. Soluble Type I collagens were isolated from the scale and bone (skull) of lathyritic carp. Each tissue collagen was assumed to consist of two different molecular forms, (alpha 1)2 alpha 2 as a main component and alpha 1 alpha 2 alpha 3 as a minor one. 2. The possible coexistence of these two forms in soluble Type I collagen of carp was previously observed for skin and muscle, but not for the swim bladder in which only the form of (alpha 1)2 alpha 2 was found. 3. These composite results suggest the wide distribution of alpha 1 alpha 2 alpha 3 heterotrimers in collagenous tissues of carp.

Amino Acids↗

Immunohistochemical study on perinatal development of rat superoxide dismutases in lungs and kidneys.

It has been reported that levels of antioxidant enzymes are low in fetal rat lungs and kidneys, and that they increase rapidly during late gestation. Among the antioxidant enzymes, both copper-zinc and manganese superoxide dismutases (CuZnSOD and MnSOD) are assumed to play a key role in protection against oxidative tissue injury. To determine the nature of the rapid perinatal increase in CuZnSOD and MnSOD, immunoenzyme staining was performed in the lungs and kidneys of fetal (d 18 and 20 of gestation) and neonatal (d 22) rats. The CuZnSOD and MnSOD in the homogenates were assayed by RIA, and they were found to be higher in the neonatal organs than in the respective fetal organs. The neonatal bronchiolar epithelium was stained for both CuZnSOD and MnSOD more intensely than the fetal one. The CuZnSOD staining in the neonatal alveolar wall was more intense than that in the fetal one. There was a significant reactivity for MnSOD in the neonatal, but not in the fetal, alveolar walls. In the kidneys, the reactivities for CuZnSOD and MnSOD were confined to the undifferentiated tubules. Although the tubules were increased in numbers in the neonatal kidneys, the intensity of the staining for both CuZnSOD and MnSOD was unchanged. The histochemical study disclosed that CuZnSOD and MnSOD increased in the kidneys in a manner different from that in the lungs. The low concentration of both CuZnSOD and MnSOD in the fetal lung tissues may contribute to the vulnerability to oxygen toxicity. Such changes in the concentrations in specific tissues were not delineated in the kidneys.

Age Factors↗

[Multiple sclerosis with higher cerebral dysfunction: a case report].

Higher cerebral dysfunctions such as aphasia, apraxia and agnosia have seldom been reported in multiple sclerosis (MS). 12 year-old right-handed boy felt unsteadiness of the body and headache for several days. Two months later, he had the same episode and complained of visual disturbance, and weakness and sensory disturbance on the face and the extremities. Additionally, he showed amnestic aphasia, acalculia, ideomotor apraxia, finger agnosia and right-left disorientation. Cerebrospinal fluid examinations revealed increases IgG, myelin basic protein and neuron specific enolase (11%, 25 ng/ml and 28.8 ng/ml, respectively). X-ray CT scan and MRI-CT examinations revealed sclerotic lesions on the left parietal white matter and the right mid-brain. The diagnosis was made as MS. He was treated with m-PSL (methyl-prednisolone) pulse therapy for three weeks and consecutively treated with PSL for four weeks. He recovered gradually, but visual disturbance and facial palsy remained. After seven months MRI-CT showed a high signal intensity on the left parietal white matter in spite of the disappearance of the lesion on X-ray CT scan. We suggest that these higher cerebral dysfunctions may result from the lesion of the left parietal white matter which produces a disconnection between each cortical area.

Agnosia↗

Effects of antiandrogens on growth of androgen-dependent mouse mammary tumor (Shionogi carcinoma 115) in vivo and in vitro.

Binding affinities of modified steroidal anthrasteroids, 3 beta-hydroxy-3a beta,6-dimethyl-2,3,3a,4,5,8,9,10,10a beta,11,11a beta, 11b alpha-dodecahydro-1H-cyclopenta[a]anthracene-8-one (1) and 3a beta,6-dimethyl-2,3,3a,4,5,8,9,10,10a beta,11,11a beta,11b alpha-dodecahydro-1H-cyclopenta[a]anthracene-3,8-dione (2), the steroid oxendolone and the nonsteroid AA560, for the androgen receptor (AR) of Shionogi carcinoma 115 (SC115) and their effects on the growth of SC115 were investigated in vivo and in vitro. The inhibitory effects of these compounds on testosterone 5 alpha-reductase of SC115 tissues were also measured. The relative binding affinities of these compounds were 3.17-0.03% of that of dihydrotestosterone, and their rank order was (1) greater than AA560 greater than oxendolone much greater than (2). In the presence of 10(-9) M testosterone, anthrasteroids and AA560 inhibited the growth of SC115 cells at 10(-7) M in a serum-free medium, but oxendolone did not. In the absence of testosterone, (1), (2) and oxendolone promoted cell growth at 10(-6), 10(-7) and 10(-7) M, respectively. However, AA560 nearly completely blocked cell growth at 10(-5) M. At a 2 mg daily dose for 13 days, (1) and AA560 powerfully inhibited tumor growth in castrated DS mice treated with testosterone propionate but oxendolone had almost no effect. Anthrasteroids and oxendolone showed weak but significant agonistic activity in vivo. Anthrasteroids markedly inhibited 5 alpha-reductase activity of SC115, oxendolone weakly and AA560 not at all. The remarkable antiandrogenic activities of (1) and AA560 may partially result from their higher affinities for the AR of SC115 but other yet unknown mechanisms may also contribute to these activities.

5-alpha Reductase Inhibitors↗

A developmental switch in thymic lymphocyte maturation potential occurs at the level of hematopoietic stem cells.

Hematopoietic stem cells (HSCs) isolated from mouse fetal liver, like adult HSCs, are Thy-1lo Lin- Sca-1+. Donor-derived V gamma 3+ T cells were detected in fetal thymic lobes repopulated in vitro with fetal liver HSCs, but not in those with adult bone marrow HSCs. Single clonogenic fetal HSCs gave rise to thymic progeny that include V gamma 3+, other gamma delta+, and alpha beta+ T cells. No V gamma 3+ T cells were detected in adult thymus injected intrathymically with either fetal or adult HSCs. These results support the hypothesis that only fetal HSCs have the capacity to differentiate into V gamma 3+ T cells in the fetal thymic microenvironment and that the developmental potential of HSCs may change during ontogeny.

Animals↗

The relation between EEG and mental development following cardiac surgery performed under simple deep hypothermia in children.

In order to assess the accuracy of electroencephalography (EEG), in children who have undergone cardiac surgery under simple deep hypothermia, the relation between IQ or schoolwork achievement and the duration of circulatory arrest was investigated in 75 such children. Abnormal preoperative EEG's were found in 16 per cent of the children while abnormal postoperative EEG's were found in 17 per cent. The children were divided into 4 groups, according to pre- and postoperative EEG results. Schoolwork achievement scores ranged between 3.0 and 3.2, the difference among the groups being insignificant. Moreover, no significant shift in IQ was found among the groups. Finally, regarding the number of children who were able to go on to a higher level of education, including high school then college or university, again no significant differences were found among the 4 groups. In a comparison with the number of such children in neighboring Nagasaki prefecture able to continue on to a higher level of education, no significant differences were seen either. The findings and statistics of this investigation therefore indicate that pre- and postoperative EEG's are not always a reliable reference for assessing the prognosis of cerebral activity.

Achievement↗

Growth stimulation by androgens, glucocorticoids or fibroblast growth factors and the blocking of the stimulated growth by antibody against basic fibroblast growth factor in protein-free culture of Shionogi carcinoma 115 cells.

Shionogi carcinoma 115 (SC115) has been accepted for 20 years as an androgen-responsive mouse mammary tumor. We have established an androgen-dependent cloned cell line (SC-3) from a SC115 tumor. In a serum-free medium, testosterone (T) or fibroblast growth factors (FGFs) markedly stimulate the growth of SC-3 cells, and the T-induced growth was shown to be mediated through FGF-like peptide(s) in an autocrine mechanism. Since we used the serum-free culture including 0.1% bovine serum albumin (BSA), a partially serum-containing condition, putative roles of BSA- or serum-borne growth factors in growth stimulation of autocrine production of FGF-like peptide(s) could not be excluded. This paper reports findings performed in a protein-free medium including plating [Ham's F-12:MEM (1:1; v/v)]. In the protein-free culture, the growth of SC-3 cells was significantly stimulated by the addition of greater than or equal to 10(-10) M T (up to 20-fold), greater than or equal to 10(-7) M dexamethasone (Dex; up to 7-fold) or greater than or equal to 1 ng/ml basic (b) or acidic FGF (up to 10-fold); other various growth factors had no such effects. Furthermore, DNA synthesis of SC-3 cells induced by T, Dex or bFGF was similarly and markedly inhibited by bFGF neutralizing antibody IgG. Therefore, the present findings seem to demonstrate that androgens or high levels of glucocorticoids induce the production and secretion of FGF-like peptide(s) from SC-3 cells for their growth even in the absence of additional support by other factors.

Androgens↗

Antioxidant enzymes and lipoperoxide in blood in patients with Kawasaki disease. Comparison with the changes in acute infections.

Increased production of active oxygen species from activated neutrophils is postulated to contribute to endothelial damage in Kawasaki disease, leading to the formation of coronary aneurysms. To determine whether an altered oxidant-antioxidant balance exists in acute phase of Kawasaki disease, antioxidant enzymes in peripheral blood cells and plasma lipid peroxide were measured in patients. The two isoenzymes of intracellular superoxide dismutase were assayed by specific radioimmunoassays. Lipid peroxide in plasma and manganese superoxide dismutase in both polymorphs and lymphocytes were increased in the acute phase of Kawasaki disease. The erythrocyte glutathione peroxidase and catalase were also increased. On the other hand, copper zinc superoxide dismutase in polymorphs, lymphocytes and erythrocytes was unaltered. Acute infections did not appear to modify the levels of either antioxidant enzymes or lipid peroxide in blood. These results suggest that increased oxidative stress in Kawasaki disease evokes a reactive increase in antioxidant enzymes, and that this response in the defense system is related to the reversible nature of the tissue damage in most patients with Kawasaki disease.

Acute Disease↗

Long-term follow-up study of children developmentally retarded by early environmental deprivation.

In 1972, two children representing a case of severe developmental retardation were discovered and taken into custody. The children, an older sister (referred to as F) and a younger brother (referred to as G), were found to have achieved no more than the physical and mental age level normal to children 1 year of age or less, in spite of their actual respective chronological ages of 6 and 5. Investigation revealed that the children's developmental retardation was due both to extreme social isolation and to complex deprivation. By following their sensorimotor, linguistic, cognitive, and socio-emotional development from the time of discovery to the date of this writing, we have found that their physical and motor development or recovery has proceeded smoothly, whereas their linguistic and cognitive development has continued to show such weaknesses as defective functioning of internal speech (Vygotsky, 1962) and poor ability to deal with abstract, linguistic subjects. F and G have continued to exhibit a tendency toward undersocialization, but this has at times been rather a positive factor in the process of attaining ego identity during adolescence, especially for G, serving to protect him from unreasonable social pressures to conform to group behavior. In combination with other cases of severe deprivation, the case of F and G holds some interesting implications for theories of human development, particularly the notion of critical periods.

Child↗

Inhibitory effect of antibody against basic fibroblast growth factor on androgen- or glucocorticoid-induced growth of Shionogi carcinoma 115 cells in serum-free culture.

Shionogi carcinoma 115 (SC115) has been accepted for 20 years as an androgen-responsive mouse mammary tumor. However, we and others recently found that the growth of SC115 cells is also stimulated by high doses of glucocorticoids. We already reported the following findings. In a serum-free medium [Ham's F-12: Eagle's minimum essential medium (1:1, v/v) containing 0.1% bovine serum albumin], greater than or equal to 10(-9) M testosterone and greater than or equal to 10(-8) M dexamethasone significantly stimulated the growth of SC-3 cells (a cloned cell line from a SC115 tumor) through androgen and glucocorticoid receptors, respectively. In the present study, we have demonstrated that higher concentrations (10(-7)-10(-6) M) of weak androgens such as 4-androstene-3,17-dione or weak glucocorticoids such as corticosterone also significantly stimulate the growth of SC-3 cells and that their relative potency is found to be in parallel with their binding affinity for their receptors, respectively. Furthermore, DNA synthesis of SC-3 cells induced by 0.1 ng/ml basic fibroblast growth factor (FGF), 10(-8) M testosterone, 10(-6) M 4-androstene-3,17-dione, 10(-7) M dexamethasone, or 10(-6) M corticosterone was found to be similarly and significantly inhibited by the addition of basic FGF neutralizing antibody IgG in the present study; approximately 70% inhibition of the basic FGF, androgen, or glucocorticoid effects was attained. We already reported findings which suggest that SC-3 cells produce FGF-like peptide for their testosterone-induced growth. Therefore, the present study presents new additive information to demonstrate that the growth-stimulatory activity of various androgens or possibly glucocorticoids on SC-3 cells is mediated through a FGF-like peptide in an autocrine mechanism.

Androstenedione↗

Androgen dependency of a tumor produced by a cell line derived from androgen-responsive Shionogi carcinoma 115.

An androgen-dependent tumor (SCC8 tumor) was obtained by inoculating an androgen-responsive cell line derived from the androgen-responsive Shionogi carcinoma 115 (SC115) into mice and then treating the mice with testosterone propionate (TP) at a pharmacological dose (400 micrograms/day). The SCC8 tumor differed in histological appearance from the SC115 tumor and its growth was less stimulated by androgen than that of the SC115 tumor. However, its growth was completely androgen dependent; SCC8 tumors did not develop in castrated mice and regressed when TP treatment was discontinued. The decreased sensitivity of the SCC8 tumor seemed to be attributable in part to its rapid metabolism of testosterone to metabolites with lower androgenic actions. The effects of TP at doses of 0, 100, 200, and 400 micrograms/day on cell division and cell death in SCC8 tumors of medium size were examined by measurements of the mitotic index and the retention of 5-[125I]iodo-2'-deoxyuridine incorporated into the whole tumor. TP increased the mitotic index dose dependently and at all doses reduced the decrease in the retention of 5-[125I]iodo-2'-deoxyuridine. These results suggest that steroids may not only stimulate cell division but also reduce cell death in steroid-dependent tumors.

Androgens↗