[Surgical treatment of patients with pulmonary aspergilloma].
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Adult↗
Biomedical subjects
Y Sagara
Publications and source records attributed to Y Sagara.
Postmenopausal hormone replacement therapy use and risk of endometrial cancer in Japanese women.
The relationship between the risk of endometrial cancer and the use of noncontraceptive estrogens by Japanese postmenopausal women was investigated in a hospital-based case-control study of 1025 women with endometrial cancer and 1267 with other conditions. The overall odds ratio (OR) for estrogen use with or without progestins, compared with never use of any type of estrogens, was 0.917 (95% confidence interval (CI) 0.622-1.353), suggesting that hormone replacement therapy is not a causative agent for endometrial cancer in Japanese women, and that a recent increase in the incidence of endometrial cancer in Japanese women may be related to changes in their life-style. However, although not statistically significant, women who used estrogen without progestin for 12 or more months had an OR of 2.552 (CI 0.231-28.192), while those who used estrogen with progestin for 12 or more months had an OR of 0.425 (CI 0.086-2.113). These results indicate that the addition of a progestin should be considered for reducing the risk of endometrial cancer in Japanese women.
Asian People↗
Co-expression of epidermal growth factor receptor and transforming growth factor-alpha predicts worse prognosis in breast-cancer patients.
Epidermal growth factor receptor (EGF-R) and its ligand, transforming growth factor-alpha (TGF-alpha), play an important role through the autocrine growth-regulation system in several human cancers, including breast cancer. However, the clinical significance of co-expression of EGF-R and TGF-alpha has not been elucidated. One hundred seventy-three female patients diagnosed as invasive ductal carcinoma who had undergone a mastectomy (159 patients) or breast-conserving surgery (14 patients) were followed up for 81 to 119 months (median 94 months) post-operatively. Immunoreactivity for EGF-R, TGF-alpha, p53 and c-erbB-2 with paraffin-embedded carcinoma tissue was investigated using labeled streptavidin-biotin methods. Positive rates of carcinoma cells were 27%, 33%, 32% and 26% for EGF-R, TGF-alpha, p53 and c-erbB-2, respectively. Expression of EGF-R only was observed in 16% (28/173), of TGF-alpha only in 22% (38/173), of both EGF-R and TGF-alpha in 11% (19/173) and of neither in 51% (88/173). By univariate analysis, significant differences in overall survival and disease-free survival were noted according to the co-expression of EGF-R and TGF-alpha (p< 0.0001, p<0.0001), co-expression of EGF-R and c-erbB-2 (p = 0.0029, p = 0.0028), nodal status (p = 0.0028, p = 0.0001), tumor size (p = 0.0001, p<0.0001) and c-erbB-2 expression (p = 0.0034, p = 0.018), respectively. The status of p53 expression (p = 0.01), estrogen receptor (p = 0.042) and progesterone receptor (p = 0.046) showed significant differences in overall survival. According to Cox's multivariate analysis, co-expression of EGF-R and TGF-alpha had the most significant effect on disease-free survival (p<0.0001) and overall survival (p<0.0001), followed by nodal status. Co-expression of EGF-R and TGF-alpha by immunohistochemical detection is an independent prognostic indicator, and it may be helpful for determining the group of breast-cancer patients with an aggressive phenotype.
Adult↗
HTLV type 1 envelope glycoprotein gp46 evokes necrosis by binding to receptor complex.
In syncytium formation induced by HTLV-1-bearing cells, 71-kDa heat shock cognate protein (HSC70) functions as a receptor molecule and the receptor complex with beta-actin and palmitoyl(16:0)-oleoyl(18:1)-phosphatidylglycerol (PG) is thus formed. We now have evidence that the molecular association between HTLV-1 gp46 envelope protein and HSC70 led to pore formation on the surface of target cell membrane and cell death followed. The peptide segment corresponding to the region from Asp-197 to Leu-216 (gp46-197), and which serves as a binding site to both HSC70 and PG for syncytium formation, also had cytotoxic effects on target cell MOLT-4. This cytotoxicity was due to necrosis, not apoptosis. On the other hand, two other receptor-binding sites, Lys-111 to Asp-138 on gp46 (gp46-111) and Cys-400 to Leu-429 on gp21 (gp21-400), and which bound only with PG, had no cytotoxic effects on MOLT-4 cells. The HTLV-2 peptide (gp46-194; Glu194 to Leu-213) corresponding to the region of HTLV-1 gp46-197 showed no cytotoxicity, and interacted only with PG, not with either HSC70 or beta-actin. Amino acid alterations between HTLV-1 gp46-197 and HTLV-2 gp46-194 were significant on the hydrophilic face of the amphipathic structure. Taken together, the interaction between HSC70 and gp46 of HTLV-1 through the hydrophilic face of gp46-197 may lead to pore formation in lipid bilayers to be followed by membrane fusion or cell death.
Cell Line↗
Gene expression monitoring for gene discovery in models of peripheral and central nervous system differentiation, regeneration, and trauma.
Gene expression monitoring using gene expression microarrays represents an extremely powerful technology for gene discovery in a variety of systems. We describe the results of seven experiments using Incyte GEM technology to compile a proprietary portfolio of data concerning differential gene expression in six different models of neuronal differentiation and regeneration, and recovery from injury or disease. Our first two experiments cataloged genes significantly up- or down-regulated during two phases of the retinoic acid-induced differentiation of the embryonal carcinoma line Ntera-2. To identify genes involved in neuronal regeneration we performed three GEM experiments, which included changes in gene expression in rat dorsal root ganglia during the healing of experimentally injured sciatic nerve, in regenerating neonatal opossum spinal cord, and during lipopolysaccharide stimulation of primary cultures of rat Schwann cells. Finally we have monitored genes involved in the recovery phase of the inflammatory disease of the rat spinal cord, experimental allergic encephalomyelitis, as well as those responsible for protection from oxidative stress in a glutamate-resistant rat hippocampal cell line. Analysis of the results of the approximately 70,000 data points collected is presented.
Animals↗
A protective role of the low density lipoprotein receptor-related protein against amyloid beta-protein toxicity.
In order to delineate the neuroprotective role of the low density lipoprotein receptor-related protein (LRP) against amyloid beta-protein toxicity, studies were performed in C6 cells challenged with amyloid beta-protein in the presence or absence of activated alpha(2)-macroglobulin. Toxicity was assessed via two cell viability assays. We found that this endocytic receptor conferred protection against amyloid beta-protein toxicity in the presence of activated alpha(2)-macroglobulin and its down-regulation via inhibition by receptor-associated protein or transfection of cells with presenilin 1, increased susceptibility to amyloid beta-protein toxicity. Increased surface LRP immunoreactivity in response to amyloid beta-protein challenge was associated with increased translocation of LRP from the endoplasmic reticulum to the surface, rather than from increased mRNA or protein expression. Furthermore, this translocation of LRP to the surface was mediated by a calcium/calmodulin protein kinase II-dependent signaling pathway. These studies provide evidence for a protective role of LRP against amyloid beta-protein toxicity and may explain the aggressive nature of presenilin-1 mutation in familial Alzheimer's disease.
Alzheimer Disease↗
Evidence for the cluster model of mitochondrial steroid hydroxylase system derived from dissociation constants of the complex between adrenodoxin reductase and adrenodoxin.
Using biotinylated adrenodoxin and avidin-Sepharose 4B, dissociation constants for the complex between adrenodoxin reductase and adrenodoxin in the oxidized and reduced states were determined as 50 +/- 11 and 296 +/- 44 nM, respectively. Concentrations of adrenodoxin reductase/adrenodoxin in the matrix fraction from bovine adrenal cortex, liver, and kidney mitochondria were determined to be 20.2 +/- 10.6 microM/120 +/- 23 microM, 0.17 +/- 0.06 microM/1.79 +/- 0.24 microM, and 0.40 +/- 0.23 microM/1.33 +/- 0.26 microM, respectively. The calculation of the percentage of adrenodoxin reductase in the complex form in the reduced state showed that it is higher than 99% in adrenal cortex mitochondria, providing clear evidence for the cluster model for the mitochondrial steroid hydroxylase system.
Adrenodoxin↗
Dopaminergic loss and inclusion body formation in alpha-synuclein mice: implications for neurodegenerative disorders.
To elucidate the role of the synaptic protein alpha-synuclein in neurodegenerative disorders, transgenic mice expressing wild-type human alpha-synuclein were generated. Neuronal expression of human alpha-synuclein resulted in progressive accumulation of alpha-synuclein-and ubiquitin-immunoreactive inclusions in neurons in the neocortex, hippocampus, and substantia nigra. Ultrastructural analysis revealed both electron-dense intranuclear deposits and cytoplasmic inclusions. These alterations were associated with loss of dopaminergic terminals in the basal ganglia and with motor impairments. These results suggest that accumulation of wild-type alpha-synuclein may play a causal role in Parkinson's disease and related conditions.
Animals↗
In vitro transcription system using reconstituted RNA polymerase (Esigma(70), Esigma(H), Esigma(E) and Esigma(S)) of Pseudomonas aeruginosa.
We have developed an in vitro transcription system for Pseudomonas aeruginosa genes, using RNA polymerase (RNAP) holoenzyme reconstituted with purified sigma protein and RNAP core enzyme. The RNAP core enzyme was directly purified from P. aeruginosa PAO1 cells. The sigma factors of P. aeruginosa (sigma(70), sigma(H), sigma(E) and sigma(S)) were prepared in a hexa-histidine tagged form, which were expressed in Escherichia coli and purified using a HisTrap Chelating column. The RNAP holoenzyme reconstituted from core enzyme with each sigma factor recognized correctly each of the cognate promoters. This system will be useful for the promoter analysis of many genes in P. aeruginosa.
Promoter Regions, Genetic↗
alpha-synuclein promotes mitochondrial deficit and oxidative stress.
Abnormal accumulation of the presynaptic protein alpha-synuclein has recently been implicated in the pathogenesis of Alzheimer's and Parkinson's diseases. Because neurodegeneration in these conditions might be associated with mitochondrial dysfunction and oxidative stress, the effects of alpha-synuclein were investigated in a hypothalamic neuronal cell line (GT1-7). alpha-Synuclein overexpression in these cells resulted in formation of alpha-synuclein-immunopositive inclusion-like structures and mitochondrial alterations accompanied by increased levels of free radicals and decreased secretion of gonadotropin-releasing hormone. These alterations were ameliorated by pretreatment with anti-oxidants such as vitamin E. Taken together these results suggest that abnormal accumulation of alpha-synuclein could lead to mitochondrial alterations that may result in oxidative stress and, eventually, cell death.
Animals↗
[Concurrent chemoradiotherapy using a single agent for unresectable stage III non-small cell lung cancer].
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Adenocarcinoma↗
Antithrombin therapy for severe preeclampsia: results of a double-blind, randomized, placebo-controlled trial. BI51.017 Study Group.
A double-blind, randomized, placebo-controlled trial was conducted to evaluate whether treatment with Antithrombin (AT) concentrates improved the clinical and perinatal outcome in patients with severe preeclampsia. Severe preeclamptic patients (24 to 35 weeks of gestation. Gestosis Index (GI) > or = 6 points) were randomized into two groups: 66 received AT and 67 received placebo. There were no statistical differences in the clinical profiles of the two groups. Study drugs were given intravenously once daily for 7 consecutive days. Maternal symptoms were evaluated from the difference of GI between before and after treatment, and fetal findings were evaluated from the changes of the biophysical profile score and the estimated fetal weight gain. Improvement was significantly greater in the AT group for both the GI (p = 0.020) and the estimated fetal weight gain (p = 0.029). The improvement of coagulation parameters was also evaluated. The D-dimer levels increased significantly in the placebo group (p = 0.026), but did not change in the AT group. Gestation was significantly prolonged (p = 0.007), and the number of low-birth weight infants was significantly smaller (p = 0.011) in the AT group. No adverse events related to AT were observed. It is revealed that AT concentrate therapy for preeclampsia is effective and safe, leading to an improved perinatal outcome.
Acute Disease↗
Vitamin E supplementation prevents spatial learning deficits and dendritic alterations in aged apolipoprotein E-deficient mice.
Recent studies have suggested that altered function of apolipoprotein E might lead to Alzheimer's disease via oxidative stress. In this context, the objective of this study was to determine if antioxidative treatment with vitamin E was neuroprotective in apolipoprotein E-deficient mice. For this purpose, 1-month-old control and apolipoprotein E-deficient mice received dietary vitamin E for 12 months. We showed that, compared to apolipoprotein E-deficient mice who received a regular diet, mice treated with vitamin E displayed a significantly improved behavioural performance in the Morris water maze. This improved performance was associated with preservation of the dendritic structure in vitamin E-treated apolipoprotein E-deficient mice. In addition, whilst untreated apolipoprotein E-deficient mice displayed increased levels of lipid peroxidation and glutathione, vitamin E-treated mice showed near normal levels of both lipid peroxidation and glutathione. These results support the contention that vitamin E prevents the age-related neurodegenerative alterations in apolipoprotein E-deficient mice.
Animals↗
cDNA cloning, overproduction and characterization of rat adrenodoxin reductase.
We isolated a full-length cDNA clone for rat adrenodoxin reductase (AdR). The precursor of rat AdR was predicted to consist of 34 amino-terminal residues of extrapeptide for transport into mitochondria and the following 460 residues of the mature peptide region. The deduced amino acid sequence was 70.8 and 61.8% homologous to those of bovine and human AdRs in the extrapeptide region, respectively, and 88.5% homologous to both the sequences of bovine and human AdRs in the mature peptide region. The predicted mature form of rat AdR was directly expressed in Escherichia coli, using cDNA, and was purified with a yield of 32 mg/l of culture. The purified recombinant rat AdR showed an absorption spectrum characteristic of a flavoprotein with peaks at 270, 378 and 450 nm and shoulders at 280, 425 and 474 nm. The extinction coefficient was estimated to be 10.9 mM(-1) cm(-1) at 450 nm. The absorbance ratio at 270 nm/450 nm was 7.1. From the θ(208) value in the circular dichroism spectrum, the alpha-helix content in the rat AdR was calculated to be 30%. In NADPH-cytochrome c reductase activity reconstituted with adrenodoxin (Ad), the apparent K(m) value of rat AdR for NADPH was 0.32 microM, a value significantly lower than that of bovine AdR (1.4 microM). The rat AdR showed a higher affinity to the heterologous redox partner (bovine Ad, K(m)=9.3 nM) than to the native partner (rat Ad, K(m)=16.7 nM), whereas the affinity of bovine AdR was slightly higher to the native partner (bovine Ad, K(m)=37.1 nM) than to the heterologous partner (rat Ad, K(m)=46.8 nM). The K(m) values showed a reverse correlation to the difference of pI values between the redox partners. These results indicate that AdR binds to Ad mainly by ionic interaction.
Amino Acid Sequence↗
Cloning and sequencing of rpoH and identification of ftsE-ftsX in Pseudomonas putida PpG1.
The rpoH gene encoding the heat-shock sigma factor of Pseudomonas putida was cloned by using its ability to complement the temperature-sensitive growth of the Escherichia coli rpoH mutant. The cloned DNA contained an open reading frame for a 284 amino acid sequence exhibiting high homology to the sigmaH proteins of P. aeruginosa and E. coli. Moreover, homologs to the cell division genes ftsX and ftsE were found immediately upstream of the rpoH gene.
ATP-Binding Cassette Transporters↗
Effect of steroidal saponins of Anemarrhenae rhizoma on superoxide generation in human neutrophils.
Effect of six steroidal saponins isolated from Anemarrhenae rhizoma on superoxide generation in human neutrophils was investigated. The steroidal saponins examined were anemarrhenasaponin-I (An-I), anemarrhenasaponin-Ia (An-Ia), timosaponin B-I (TB-I), timosaponin B-II (TB-II), timosaponin B-III (TB-III) and timosaponin A-III (TA-III). An-I, An-Ia, and TB-III suppressed the superoxide generations induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP) and arachidonic acid (AA) in a concentration-dependent manner, but enhanced that induced by phorbol 12-myristate 13-acetate (PMA). While TB-II also suppressed and enhanced the superoxide generations induced by fMLP and PMA, respectively, the compound significantly enhanced the AA-induced superoxide generation. TB-I enhanced the fMLP-induced superoxide generation in a low concentration range (peak at 40 microM), gave no effect on the PMA-induced superoxide generation and weakly enhanced the AA-induced superoxide generation. TA-III enhanced the fMLP-induced superoxide generation more than twice as much as that by TB-I in the same concentration range. However, TA-III enhanced the PMA-induced superoxide generation and most significantly suppressed the AA-induced superoxide generation.
Arachidonic Acid↗
D-cystathionine ketimine and L-cystathionine ketimine enhance superoxide generation by human neutrophils in a different manner.
The effects of d-cystathionine ketimine (D-CK) and l-cystathionine ketimine (L-CK) on the stimulus-induced superoxide generation by human neutrophils were compared. When the cells were preincubated with D-CK, the superoxide generation induced by arachidonic acid (AA), phorbol 12-myristate 13-acetate (PMA), and N-formyl-methionyl-leucyl-phenylalanine (fMLP) were enhanced, showing a dependence on D-CK concentration. The rate of enhancement by D-CK was AA > PMA > fMLP. On the contrary, L-CK largely enhanced the fMLP-induced superoxide generation, whereas it showed no effect on those induced by AA and PMA. The superoxide generations induced by AA and PMA in the D-CK-treated cells were suppressed by staurosporine, while those in the L-CK-treated cells were not affected. Genistein suppressed the fMLP-induced superoxide generation in the L-CK-treated cells more efficiently than that in the D-CK-treated cells. D-CK enhanced seryl phosphorylation of 16. 5-kDa protein in human neutrophils, while L-CK enhanced tyrosyl phosphorylation of 45-kDa protein.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
Surgical treatment for patients with lung cancer complicated by severe pulmonary emphysema.
Ten patients with lung cancer complicated by severe pulmonary emphysema, underwent lung reduction surgery between 1995 and 1997. Patients meeting the following criteria were defined as having severe pulmonary emphysema: (1) forced expiratory volume in 1 s (FEV1%) of < 55% and (2) characteristic, severe findings of emphysema in chest x-rays and chest computed tomography scans. 9 men and 1 woman (mean age: 70.8; range: 59-78 years), were all smokers (smoking index: 500-2450). Preoperative lung function showed an average percent vital capacity of 87.8% (range: 67-108%) and an average FEV1% of 35.9% (range: 27-54%). The histological types of lung cancer were squamous cell carcinoma (4 patients), adenocarcinoma (5 patients), and large cell carcinoma (1 patient). Four patients were in clinical stage IA, 3 in stage IB, and 1 each was in stages IIA, IIIA, and IIIB. Lobectomy was conducted in 3 cases and partial resection in the remaining 7. Five of the 10 patients underwent thoracoscopic resection. After surgery, patients died one at 2 months and the other at 17; 3 survived but 3 suffered cancer recurred; and 5 patients without recurrence. In complications, bronchial air leakage requiring postoperative treatment. Postoperative lung function showed an average percent vital capacity of 71.4% (range: 41-90%) and an average FEV1% of 41.3% (range: 28-61%). We found an important relationship between the location of the perfusion defect (target area) in pulmonary perfusion scintigram in relation to the lung cancer site and postoperative improvement of lung function. One patient with lung cancer associated with severe respiratory obstruction underwent lobectomy after confirmation of the perfusion defect by pulmonary perfusion scintigram. Postoperative FEV1% in this patient was restored to the preoperative level. In general, partial thoracoscopic resection was effective in patients with early-stage lung cancer.
Adenocarcinoma↗