Biomedical subjects

Y Sagara

Publications and source records attributed to Y Sagara.

At least 73 records · Page 4Linked to original sources

PubMed1998

Effect of estrogen and simvastatin on low-density lipoprotein subclasses in hypercholesterolemic postmenopausal women.

OBJECTIVE: To identify the effects of estrogen and simvastatin, individually and in combination, on the levels of low-density lipoprotein (LDL) subclasses in postmenopausal women with type IIa hypercholesterolemia. METHODS: Fifty-five postmenopausal women with type IIa hypercholesterolemia were assigned randomly to 0.625 mg of conjugated equine estrogen (n = 20), 5 mg of simvastatin (n = 18), or both (n = 17) daily for 3 months. Cholesterol, triglyceride, and apolipoprotein B levels in the plasma and in the LDL1 (density 1.019-1.045 g/mL) and LDL2 (density 1.045-1.063 g/mL) fractions were measured before and after treatment. RESULTS: Estrogen treatment significantly reduced LDL1 cholesterol and LDL1 apolipoprotein B levels by 18.4% and 20.8%, respectively; simvastatin treatment by 21.9% and 29.2%, respectively; and combination therapy by 38.5% and 34.4%, respectively. In contrast to estrogen or simvastatin treatment, the combination therapy also significantly lowered the levels of LDL2 cholesterol by 19.5% and LDL2 apolipoprotein B by 30.5%. Posttreatment levels of total cholesterol, LDL1 cholesterol, and LDL1 apolipoprotein B were significantly lower after combination treatment than after estrogen treatment. Estrogen treatment, but not combination therapy, significantly increased total plasma triglyceride levels (103.1+/-26.0 mg/dL to 138.8+/-75.6 mg/dL, P < .01). Significantly more patients receiving combination therapy than those receiving estrogen had total and LDL cholesterol concentrations reduced to target levels. CONCLUSION: Combination therapy with estrogen and simvastatin favorably affected lipid metabolism by reducing large and small LDL particles and prevented the estrogen-induced increase in plasma triglyceride levels.

Estrogens, Conjugated (USP)↗

PubMed1998

Cellular mechanisms of resistance to chronic oxidative stress.

Oxidative stress is implicated in several pathologies such as AIDS, Alzheimer's disease, and Parkinson's disease, as well as in normal aging. As a model system to study the response of cells to oxidative insults, glutamate toxicity on a mouse nerve cell line, HT-22, was examined. Glutamate exposure kills HT-22 via a nonreceptor-mediated oxidative pathway by blocking cystine uptake and causing depletion of intracellular glutathione (GSH), leading to the accumulation of reactive oxygen species and, ultimately, apoptotic cell death. Several HT-22 subclones that are 10-fold resistant to exogenous glutamate were isolated and the mechanisms involved in resistance characterized. The expression levels of neither heat shock proteins nor apoptosis-related proteins are changed in the resistant cells. In contrast, the antioxidant enzyme catalase, but not glutathione peroxidase nor superoxide dismutase, is more highly expressed in the resistant than in the parental cells. In addition, the resistant cells have enhanced rates of GSH regeneration due to higher activities of the GSH metabolic enzymes gamma-glutamylcysteine synthetase and GSH reductase, and GSH S-transferases activities are also elevated. As a consequence of these alterations, the glutamate resistant cells are also more resistant to organic hydroperoxides and anticancer drugs that affect these GSH enzymes. These results indicate that resistance to apoptotic oxidative stress may be acquired by coordinated changes in multiple antioxidant pathways.

Animals↗

PubMed1998

Induction of reactive oxygen species in neurons by haloperidol.

Haloperidol (HP) is widely prescribed for schizophrenia and other affective disorders but has severe side effects such as tardive dyskinesia. Because oxidative stress has been implicated in the clinical side effects of HP, rat primary cortical neurons and the mouse hippocampal cell line HT-22 were used to characterize the generation of reactive oxygen species (ROS) and other cellular alterations caused by HP. Primary neurons and HT-22 cells are equally sensitive to HP with an IC50 of 35 microM in the primary neurons and 45 microM in HT-22. HP induces a sixfold increase in levels of ROS, which are generated from mitochondria but not from the metabolism of catecholamines by monoamine oxidases. Glutathione (GSH) is an important antioxidant for the protection of cells against HP toxicity because (1) the intracellular GSH decreases as the ROS production increases, (2) the exogenous addition of antioxidants, such as beta-estradiol and vitamin E, lowers the level of ROS and protects HT-22 cells from HP, and (3) treatments that result in the reduction of the intracellular GSH potentiate HP toxicity. The GSH decrease is followed by the increase in the intracellular level of Ca2+, which immediately precedes cell death. Therefore, HP causes a sequence of cellular alterations that lead to cell death and the production of ROS is the integral part of this cascade.

Animals↗

PubMed1998

Estrogen receptor mutations and changes in estrogen receptor and progesterone receptor protein expression in metastatic or recurrent breast cancer.

To investigate the frequency of estrogen receptor (ER) gene mutation in metastatic or recurrent breast cancer, metastatic lymph nodes or recurrent breast cancer tissue from 35 patients with ER-positive primary tumors were screened for mutations in the hormone-binding domain of the ER gene by sequence analysis. Four missense mutations, Val316Ile, Gly344Val, Ala430Val and Gly494Val, were identified in these lesions. Second, to clarify whether there is any disparity in hormone receptor status between primary and metastatic or recurrent tumors, we immunohistochemically studied 117 specimens including the above 35 specimens obtained from metastatic or recurrent breast cancer patients using monoclonal anti-ER and progesterone receptor (PgR) antibodies. Although hormone receptor status, especially ER, was highly maintained through disease progression, negative change in PgR expression at relapse (33%) was identified more frequently than in metastatic lymph nodes (6.7%). Therefore, it was suggested that development of PgR-negative phenotype might correlate with disease progression in some breast cancer patients. These results suggest that ER mutations in metastatic or recurrent breast cancer may be more frequent than in primary lesions, irrespective of high maintenance of ER protein expression through disease progression.

Breast Neoplasms↗

PubMed1998

Histological and biological characteristics of microinvasion in mammary carcinomas < or = 2 cm in diameter.

Fifty-two mammary carcinomas, 2 cm or less in diameter, were examined in order to clarify the morphology and biology of microinvasion. The morphological characteristics of microinvasion of carcinomas include: (i) a loss of myoepithelial cells and a rupture with concomitant loss of collagen IV and laminin in the basement membrane of involved mammary glands; and (ii) budding of carcinomas from the rupture into the stroma. When microinvasion was defined as a rupture of < 200 microm in the basement membrane with invasion, the number of microinvasions per 1 mm of basement membrane was larger in the tumors in which the area of invasion was larger. The prevalence of microinvasion showed a significant correlation with lymph node metastasis and the rate of histological deviation, while no correlation of expression of either estrogen receptors or progesterone receptors and c-erbB-2 protein was found. The study clarified that the early invasion of mammary carcinomas could be detected by the immunohistochemical method using anti-smooth muscle actin, laminin and collagen IV antibodies. The study also suggested that microinvasion might be an indicator of lymph node metastasis in mammary carcinomas < or = 2 cm diameter.

Adenocarcinoma, Papillary↗

PubMed1998

The expression of thymidine phosphorylase/platelet-derived endothelial cell growth factor is correlated to angiogenesis in breast cancer.

It has been shown that human thymidine phosphorylase (TP) is identical to platelet-derived endothelial cell growth factor and has angiogenic activity. In the present study, the expression of TP was examined in 139 mammary carcinomas and 35 benign mammary disorders using biochemical and immunohistochemical methods. Moreover, in order to evaluate the significance of TP expression in mammary carcinomas, the relationship between vascular density and various clinicopathological factors, including age and menopausal status of patients with a mammary carcinoma, were compared with the size, nodal status, expression of estrogen receptor (ER), progesterone receptor (PgR), c-erbB-2, p53 and TP of a mammary carcinoma. Thymidine phosphorylase expression increased in both the nuclei and cytoplasm of mammary carcinoma cells in comparison to mammary benign disorder cells. The number of microvessels in mammary carcinomas was generally correlated to the number of tumor cells with TP expression in cytoplasm. The number of cells with TP expression in cytoplasm was significantly large in tumors that measured 3-4 cm in diameter, compared with tumors measuring 1-2 and 5-6 cm in diameter. In mammary tumors of 1-4 cm diameter, TP expression and vessel density were significantly high in tumors negative for ER or positive for c-erbB2 and in tumors positive for TP or c-erbB2, respectively; whereas tumors of 5-6 cm in diameter were not modified by any clinicopathological factors. The results indicated that TP plays an important angiogenetic role in mammary carcinomas, especially tumors with a certain progression.

Adult↗

PubMed1998

Primary ovarian angiosarcoma: a case report and literature review.

Primary ovarian angiosarcoma is extremely rare. Only 16 cases have histologically been reported to date in the literature. A case of angiosarcoma arising in the right ovary of a 46-year-old female is presented. Grossly, the resected right ovary was completely replaced by a solid tumor mass, which revealed multiple necrotic and/or hemorrhagic foci. This case revealed the typical histological features of angiosarcoma with sinusoidal and solid patterns of anaplastic tumor cells. Immunohistochemically, tumor cells were strongly and diffusely positive for CD31 and CD34, in particular, along the cytoplasmic membrane of the tumor cells. Ultrastructurally, tumor cells possessed the intermediate junctions between tumor cells, discontinuous basal laminae attached to the irregularly shaped blood vessels and occasional cytoplasmic pinocytotic vesicles. These findings confirmed the case as being one of angiosarcoma of the ovary. The patient died 9 months after surgery as a result of developed multifocal brain metastases. A total of 17 cases reported as primary ovarian angiosarcoma, including this presented case, are clinicopathologically reviewed.

Antigens, CD34↗

PubMed1998

Immunohistochemical studies on expression of human vascular smooth muscle myosin heavy chain isoforms in normal mammary glands, benign mammary disorders and mammary carcinomas.

The expression of myosin in normal and diseased mammary glands of 199 Japanese women was evaluated immunohistochemically by the avidin-biotin peroxidase complex method using antibodies to three human smooth muscle myosin heavy chain isoforms derived from the vascular smooth muscle: myosin SM1 is expressed consistently from fetal stage to adulthood, myosin SM2 appears only in well-differentiated smooth muscle after birth, and myosin SMemb is more abundant in embryonic aortas. SM1 was expressed in myoepithelial cells of normal mammary glands and fibrocystic diseases and in myoepithelial-like tumor cells in the basal layer of fibroadenomas and phyllodes tumors. SM2 was expressed only in the myoepithelial cells of mammary glands in breastfeeding women. SMemb was expressed more intensely in the cytoplasm of luminal epithelial cells in larger fibroadenomas (P< 0.01), or in the cytoplasm of carcinoma cells in invasive ductal carcinomas with metastasized lymph nodes (P< 0.001) and in those of higher histological grade (P<0.0001). Multivariate logistic analysis showed a significant correlation only between the expression of SMemb and histological grade (P< 0.0001), which is a prognostic factor of mammary carcinomas. These findings suggested the possible prognostic value of SMemb.

Adolescent↗

PubMed1998

Effect of estrogen on melatonin synthesis in female peripubertal rats.

Our objective was to evaluate the effect of estrogen on the synthesis of melatonin in female rats during the peripubertal period. The level of melatonin and of N-acetyl serotonin (NAS) and the activity of N-acetyltransferase (NAT) and of hydroxy-indole-O-methyltransferase (HIOMT) were determined in homogenates of pineal glands from peripubertal female Sprague-Dawley rats in the mid-dark during the daily light/dark cycle between 4 and 10 weeks of age. Ovariectomy was performed and daily administration of estradiol benzoate (E2B) was initiated at 6 weeks of age. A peak in the pineal level of melatonin and NAS and in NAT activity was observed in untreated (control) rats with intact ovaries at 6 weeks. Thereafter, HIOMT activity increased and remained unchanged. Ovariectomy at week 6 led to significant increases in the level of melatonin and of NAS and in NAT activity at week 8. At week 10, NAT activity was similar to that of control animals, but melatonin and NAS levels were slightly elevated. Ovariectomy did not affect HIOMT activity. The subcutaneous injection of a low dose (0.1 microg/day) of E2B suppressed the ovariectomy-induced elevation of levels of melatonin and NAS and of NAT activity, similar to that seen in rats with intact ovaries. A higher dose of E2B (1.0 microg/day) reduced the activity of NAT and HIOMT to values significantly below the control values. Results suggest that estrogen modulates the nocturnal synthesis of melatonin by the pineal gland in peripubertal female rats. The decline in melatonin synthesis during puberty may be related to an increase in the estrogen level. The inhibitory effect of estrogen in melatonin synthesis appeared to be mediated by the modulation of NAT activity.

Acetylserotonin O-Methyltransferase↗

PubMed1998

Effect of estrogen on melatonin synthesis in female peripubertal rats as related to adenylate cyclase activity.

To determine the mechanism for the modulatory effect of estrogen on melatonin synthesis, we evaluated the effects of estrogen on the activity of adenylate cyclase in female Sprague-Dawley rats of peripubertal age. Adenylate cyclase activity was measured in homogenates of pineal glands from rats aged 3 and 10 weeks in the mid-dark and in the mid-light. Ovariectomy was performed and a subcutaneous injection of estradiol benzoate (E2B) was administered daily starting at the age of 6 weeks. A peak in adenylate cyclase activity in the pineal gland was observed in untreated (control) rats with intact ovaries at 4 weeks. Ovariectomy at week 6 led to significant increases in the activity of adenylate cyclase at week 8. At week 10, adenylate cyclase activity resembled that of control animals. The subcutaneous injection of E2B (1.0 microg/day) suppressed the increase in adenylate cyclase activity induced by ovariectomy, similar to the level seen in control rats with intact ovaries. The changes in the mid-light activity of pineal adenylate cyclase resembled that seen at the mid-dark with the value being significantly lower than that observed in the mid-dark. Such changes in the mid-dark activity of adenylate cyclase resembled those observed with N-acetyltransferase (NAT) at the same time, as previously described. Results suggest that estrogen modulates adenylate cyclase activity in the pineal gland of peripubertal female rats. The decline in melatonin synthesis during puberty may be related to an increase in estrogen level. The inhibitory effect of estrogen on melatonin synthesis appeared to be mediated by a change in the norepinephrine-induced stimulation of pineal adenylate cyclase activity.

Adenylyl Cyclases↗

PubMed1998

Estrogen modulates the nocturnal synthesis of melatonin in peripubertal female rats.

Our objective was to evaluate the effects of estrogen deficit and of estrogen stimulation on the synthesis of pineal melatonin in female rats during the peripubertal period. The levels of melatonin and N-acetylserotonin (NAS) and the activities of N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT) were determined in homogenates of pineal glands obtained from peripubertal female Sprague-Dawley rats 4 to 12 weeks of age in the mid-dark during the daily light/dark cycle. Animals were ovariectomized at 4 weeks of age; daily administration of estradiol benzoate (E2B, 1.0 microg/d, s.c.) was initiated at 4 weeks of age. A peak in the pineal levels of melatonin and NAS and in NAT activity was observed in untreated (control) rats with intact ovaries at 6 weeks. HIOMT activity increased from Week 4 to 6 and remained unchanged thereafter. Ovariectomy at Week 4 led to significant increases in the levels of melatonin and of NAS and NAT in activity at Week 8. NAT activity Week 10 resembled that of control animals, but levels of melatonin and NAS were slightly elevated. Ovariectomy did not affect HIOMT activity. Subcutaneous injection of E2B significantly decreased the levels of melatonin and NAS and of NAT activity at Week 4, as compared with those in control rats. E2B suppressed the ovariectomy-induced elevation of levels of melatonin and NAS and of NAT activity, similar to the effect in control animals. E2B did not affect HIOMT activity. Our results suggest that estrogen modulates the nocturnal synthesis of melatonin in the pineal gland in peripubertal female rats. The effects of estrogen on melatonin synthesis appeared to be mediated by the modulation of NAT activity.

Acetylserotonin O-Methyltransferase↗

PubMed1998

Maternal-fetal transfer of melatonin in pregnant women near term.

Our objective was to evaluate the maternal-fetal transfer of melatonin in pregnant women. Serum melatonin concentration was measured by high-performance liquid chromatography with electrochemical detection in a maternal vein and in the umbilical artery and umbilical vein at the time of birth. Blood samples were obtained from 12 women who had spontaneously delivered vaginally at night. A single oral dose of melatonin was administered to each of 33 patients who underwent a cesarean section, and, blood samples were taken at 1, 2, 3, or 4 hr after the administration of melatonin at delivery. Cesarean section was performed between 1300 and 1500 hr. The mean melatonin concentrations of melatonin in maternal peripheral venous blood and umbilical arterial and umbilical venous blood did not differ significantly, and positive correlations in the serum levels of melatonin were observed between the three sources of blood. The oral administration of 3 mg of melatonin to pregnant women led to marked increases in the serum levels of melatonin, with maximum levels observed 2 hr (21.84 +/- 2.09 ng/ml) after drug administration. Changes in serum levels of melatonin in the umbilical vein and artery resembled those found in the maternal vein. Serum melatonin concentrations did not differ significantly between the maternal vein and the umbilical veins. Serum levels of melatonin in the umbilical vein after the administration of melatonin were significantly and closely correlated with those in the maternal vein (r = 0.924, P < 0.001). These results suggest that, in humans, melatonin is transferred from the maternal to the fetal circulation both easily and rapidly. A potential for the therapeutic use of melatonin as an antioxidant exists in the patients with preeclampsia.

Adolescent↗

PubMed1998

71-kilodalton heat shock cognate protein acts as a cellular receptor for syncytium formation induced by human T-cell lymphotropic virus type 1.

We previously reported that the region corresponding to amino acids 197 to 216 of the gp46 surface glycoprotein (gp46-197) served as a binding domain for the interaction between gp46 and trypsin-sensitive membrane components of the target cell, leading to syncytium formation induced by human T-cell lymphotropic virus type 1 (HTLV-1)-bearing cells. Our new evidence shows that the 71-kDa heat shock cognate protein (HSC70) acts as a cellular receptor for syncytium formation. Using affinity chromatography with the peptide gp46-197, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, we isolated three components (bands A, B, and C) from MOLT-4 cell lysate which exhibited specific interactions with gp46 and inhibitory activities for syncytium formation induced by HTLV-1-bearing cells. Band A and B components were identified as HSC70 and beta-actin, respectively, through amino acid sequencing by tandem mass spectrometry and immunostaining with specific monoclonal antibodies. Band C is likely to be a nonprotein component, because full activity for syncytium formation was seen after extensive trypsin digestion. Anti-HSC70 monoclonal antibody clearly blocked syncytium formation in a coculture of HTLV-1-bearing cells and indicator cells, whereas no inhibition was seen with anti-beta-actin monoclonal antibody. Furthermore, flow cytometric analysis indicated that anti-HSC70 antibody reacted with MOLT-4 cells. Thus, we propose that HSC70 expressed on the target cell surface acts as a cellular acceptor to gp46 exposed on the HTLV-1-infected cell for syncytium formation, thereby leading to cell-to-cell transmission of HTLV-1.

Amino Acid Sequence↗

PubMed1998

Overproduction in Escherichia coli and characterization of the precise mature form of rat adrenodoxin.

The mature form of rat adrenodoxin (Ad) was purified from a heterologous direct expression system in Escherichia coli with a yield of 56 mg/l culture. The purified Ad showed a A414/A280 ratio of 0.91 and the sequence of 10 amino terminal residues was identical with that of authentic rat Ad. By Time of Flight/Mass spectrometry, the molecular mass of purified Ad was identical to that calculated from the cDNA sequence and the carboxy terminal residue was estimated to be Ser, which was also as expected from the cDNA. These results indicate that the purified recombinant Ad is a precise mature form. In measurements of NADPH-cytochrome c reductase activity reconstituted with bovine adrenodoxin reductase (AdR), the apparent Km value for rat Ad was 46.9+/-2.5 nM, indicating a somewhat lower affinity for rat Ad to bovine AdR than for bovine Ad. On the other hand, the spectral Kd value for rat Ad to bovine cytochrome P-450scc was 0.46+/-0.05 microM, a value which was almost identical with that of the bovine counterpart.

Adrenodoxin↗

PubMed1998

Effects of superoxide and peroxynitrite on vascular tension in the human umbilical artery.

BACKGROUND: While nitric oxide (NO) has been demonstrated to regulate vascular tone, superoxide (O2-) may also have an important role in regulating tension in the human fetoplacental vasculature. We therefore evaluate the effects of O2- and peroxynitrite (ONOO-) on vascular tension in isolated human umbilical arteries. METHODS: Helical sections of umbilical arteries were obtained from healthy pregnant women who were delivered between weeks 37 and 39 of gestation. Changes in maximal potassium chloride (KCl)-induced tension were measured in umbilical artery segments with intact endothelium. RESULTS: We found that hypoxanthine plus xanthine oxidase significantly potentiated vascular tension, and that this effect was suppressed by pretreatment with L(NG)-monomethyl arginine (LNMA). Pretreatment with hypoxanthine plus xanthine oxidase, however, significantly inhibited the relaxation induced by the calcium ionophore A23187. 3-morpholinosydomine (SIN-1), which releases O2- and NO simultaneously produced a significant dose-dependent relaxation of vascular tension, which pretreatment with hemoglobin did not affect SIN-1-induced relaxation. Pretreatment with methylene blue significantly attenuated, while pretreatment with superoxide dismutase (SOD) significantly potentiated this effect. CONCLUSION: These findings suggest that O2- potentiates vascular tension in human umbilical artery, in part, by suppressing NO synthesis in the endothelium. The vasorelaxation by exogenously generated ONOO suggests that this moiety has biological relevance in vasoregulation of the human umbilical artery.

Female↗

PubMed1998

[Lung cancer in patients with sequelae of tuberculosis].

To clarify features of lung cancer in patients with tuberculosis sequelae, we analyzed data on 15 cases (5.1%) who were diagnosed with lung cancer before death among 294 deceased cases with tuberculosis sequelae at our hospital. There were 12 men and 3 women, with a mean age of 64 years. Most of the 15 patients had pulmonary dysfunction, and 4 had received home oxygen therapy. All 12 men had a history of smoking, and 10 of them had squamous cell carcinoma of the lung. There was no definite correlation between the locations of the tuberculosis lesion and those of lung cancer lesion on chest X-rays. Twelve patients had had thoracoplasty for tuberculosis, and in 6 of these patients the lung cancer occurred in the same lung. Lung cancer was apt to be diagnosed in an advanced stage. However, in patients who received home oxygen therapy, diagnosis had been made at an early stage because of the frequent chest X-ray follow-up. We conclude that lung cancer is an important complication in patients with tuberculosis sequelae, and early diagnosis of lung cancer by careful follow-up is essential in the care of cases with tuberculosis sequelae who have poor pulmonary function and/or systemic conditions.

Aged↗

PubMed1997

Priming effect of N-acetyl-S-(3-oxo-3-carboxy-n-propyl)cysteine in human neutrophils and tyrosyl phosphorylation of 45 kDa protein.

Human peripheral blood polymorphonuclear leukocytes were preincubated with N-acetylcystathionine and N-acetyl-S-(3-oxo-3-carboxy-n-propyl)cysteine (NAc-OCPC) found in the urine of a patient with cystathioninuria. NAc-OCPC significantly enhanced the N-formyl-methionyl-leucyl-phenylalanine-induced superoxide generation, whereas N-acetylcystathionine did not enhance the superoxide generation. When the cells were incubated with NAc-OCPC, the tyrosyl phosphorylation of 45 kDa protein of the cell was markedly increased with time. The phosphorylation process was dependent on the concentration of NAc-OCPC. Both the superoxide generation and the tyrosyl phosphorylation of 45 kDa protein increased by NAc-OCPC were inhibited by genistein and herbimycin A, the inhibitors of protein tyrosine kinase, but were rather enhanced by staurosporine, an inhibitor of protein kinase C.

Amino Acids↗

PubMed1997

Mechanism of amyloid beta protein induced neuronal cell death: current concepts and future perspectives.

Amyloid beta protein (A beta) is a 40 to 43 amino acid peptide which is associated with plaques in the brains of Alzheimer's patients and is cytotoxic to cultured neurons. A number of antioxidants protect both primary central nervous system (CNS) cultures and clonal cell lines from A beta toxicity, suggesting that one pathway to A beta cytotoxicity results in free radical damage. A beta causes increased levels of H2O2 and lipid peroxides to accumulate in cells. The H2O2 degrading enzyme catalase protects cells from A beta toxicity. Clonal cell lines selected for their resistance to A beta toxicity also become resistant to the cytolytic action of H2O2. In addition, A beta induces NF-kB activity, a transcription factor thought to be regulated by oxidative stress. Finally, A beta induced H2O2 production and A beta toxicity are blocked by reagents which inhibit flavin oxidases, suggesting that A beta activates a member of this class of enzymes. These results show that the cytotoxic action of A beta on neurons results from free radical damage to susceptible cells (Behl et al., 1994b).

Alzheimer Disease↗