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71.
Pedersen LM Terslev L SŁrensen PG Stokholm KH 《Medical oncology (Northwood, London, England)》2000,17(2):117-122
Transcapillary escape rate of albumin was determined in 22 patients with different malignancies. In addition, urinary albumin
excretion rate was measured in 24-h urine samples using a sensitive immunoassay. Increased urinary albumin excretion was defined
as ≥20 μg/min according to conventional standards. Renal glomerular filtration and tubular function was estimated by51Cr-EDTA plasma clearance and urinary beta 2-microglobulin, respectively. Median urinary albumin excretion rate was 15.0 μg/min
(range 6–510 μg/min) and the frequency of increased urinary albumin excretion was 41%. This agrees with other studies showing
increased albuminuria in several types of malignant diseases. Patients with advanced disease (tumour, node, metastasis (TNM)
stage II–IV) had a significantly higher urinary albumin excretion rate than patients with localized disease (TNM stage I).
Serum creatinine, glomerular filtration rate and urinary beta 2-microglobulin were all within normal limits. Median transcapillary
escape rate of albumin was 5.5%/h (range 2–8%/h) and this level is comparable with values in healthy subjects. There was no
significant difference in transcapillary escape rate between patients with elevated urinary albumin excretion and the normoalbuminuric
group. Median value of the absolut outflux of albumin was 10.6 g/h with similar levels in patients with increased urinary
albumin excretion and patients with normoalbuminuria. Our results indicate a high prevalence of minor glomerular dysfunction
with a slightly elevated urinary albumin excretion in patients with malignancies. The normal endothelial function, as estimated
by the transcapillary escape rate of albumin, suggests an overal unaffected capillary permeability and increased urinary albumin
loss appears to be an isolated renal phenomenon in cancer patients. 相似文献
72.
73.
Relating aromatic hydrocarbon-induced DNA adducts and c-H-ras mutations in mouse skin papillomas: the role of apurinic sites. 总被引:3,自引:0,他引:3 下载免费PDF全文
D Chakravarti J C Pelling E L Cavalieri E G Rogan 《Proceedings of the National Academy of Sciences of the United States of America》1995,92(22):10422-10426
Mouse skin tumors contain activated c-H-ras oncogenes, often caused by point mutations at codons 12 and 13 in exon 1 and codons 59 and 61 in exon 2. Mutagenesis by the noncoding apurinic sites can produce G-->T and A-->T transversions by DNA misreplication with more frequent insertion of deoxyadenosine opposite the apurinic site. Papillomas were induced in mouse skin by several aromatic hydrocarbons, and mutations in the c-H-ras gene were determined to elucidate the relationship among DNA adducts, apurinic sites, and ras oncogene mutations. Dibenzo[a,l]pyrene (DB[a,l]P), DB[a,l]P-11,12-dihydrodiol, anti-DB[a,l]P-11,12-diol-13,14-epoxide, DB[a,l]P-8,9-dihydrodiol, 7,12-dimethylbenz[a]anthracene (DMBA), and 1,2,3,4-tetrahydro-DMBA consistently induced a CAA-->CTA mutation in codon 61 of the c-H-ras oncogene. Benzo[a]pyrene induced a GGC-->GTC mutation in codon 13 in 54% of tumors and a CAA-->CTA mutation in codon 61 in 15%. The pattern of mutations induced by each hydrocarbon correlated with its profile of DNA adducts. For example, both DB[a,l]P and DMBA primarily form DNA adducts at the N-3 and/or N-7 of deoxyadenosine that are lost from the DNA by depurination, generating apurinic sites. Thus, these results support the hypothesis that misreplication of unrepaired apurinic sites generated by loss of hydrocarbon-DNA adducts is responsible for transforming mutations leading to papillomas in mouse skin. 相似文献
74.
Objective : To describe the obstetric and perinatal factors, in particular the method of delivery, associated with development of a subgaleal haematoma (SGH) and to determine the outcome of survivors with this type of birth trauma. Methodology : Perinatal and obstetric data were retrospectively reviewed for 37 infants admitted to the neonatal unit of the sole tertiary paediatric referral hospital in Western Australia with an SGH, over a 24 year period from 1970 to 1993. These data were compared to data for all Western Australian births. The long-term outcome was obtained through medical and private paediatric records for 26 of these infants. Results : All except one of the neonates had instrumental deliveries; 89% had a vacuum extractor applied to the head at some stage of delivery compared to 10% of the general population of births in Western Australia. There was also a significantly increased risk of failure of attempted vacuum extraction. Of the cases where a vacuum extraction was attempted, 45% also had forceps applied to the head. Coagulopathy was associated with the severity of the SGH. There was also a high frequency of occurrence (40%) of associated head trauma such as intracranial haemorrhage, skull fracture and cerebral oedema, as well as neonatal encephalopathy (73%). The occurrence of these associated features did not correlate significantly with the severity of SGH. Minor complications of SGH included jaundice and facial bruising. There was an excess mortality associated with SGH; however, the long-term outcome for neonatal survivors with this disorder was good. None of the cases studied subsequently developed cerebral palsy or intellectual disability, and minor neurological sequelae only were documented in four infants. Conclusions : SGH is an uncommon type of birth trauma, and is associated with delivery or attempted delivery by vacuum extraction. The most commonly associated clinical problems were hypovolaemia and coagulopathy. The long-term outcome for neonates with this condition is good. 相似文献
75.
76.
Eighteen patients with a variety of illnesses but no history of thyroid disease were shown to have elevated serum total and free thyroxine (T4) concentrations but low serum total triiodothyronine (T3) levels. Thyroid function tests were requested initially to excluded the possibility of hyperthyroidism in a setting of hypermetabolism. Clinical and laboratory follow-up investigations demonstrated that 15 patients were euthyroid and that hormonal alterations were transient features of the intercurrent illnesses. Three patients did, in fact, have hyperthyroidism. Retrospective analysis of diagnostic data demonstrated that of the initial thyroid function screening tests, serum total T3 concentration, the T3/TF4 ratio, and the indirectly measured free T3 (FT3) index were the most useful parameters in excluding hyperthyroidism. The FT3 index was the most helpful, being normal or low in all the euthyroid and high in each of the hyperthyroid patients. 相似文献
77.
Singh S Chakravarti D Edney JA Hollins RR Johnson PJ West WW Higginbotham SM Cavalieri EL Rogan EG 《Oncology reports》2005,14(4):1091-1096
Estrogens are a known risk factor for breast cancer. Studies indicate that initiation of breast cancer may occur by metabolism of estrogens to form abnormally high levels of catechol estrogen-3,4-quinones, which can then react with DNA to form depurinating adducts and, subsequently, induce mutations that lead to cancer. Among the key enzymes metabolizing estrogens are two activating enzymes: cytochrome P450 (CYP)19 (aromatase), which converts androgens to estrogens, and CYP1B1, which converts estrogens predominantly to the 4-catechol estrogens that are further oxidized to catechol estrogen-3,4-quinones. Formation of the quinones is prevented by methylation of the 4-catechol estrogens by the enzyme, catechol-O-methyltransferase (COMT). In addition, catechol estrogen quinones can be reduced back to catechol estrogens by NADPH quinone oxidoreductase 1 (NQO1) and/or are coupled with glutathione, preventing reaction with DNA. Thus, COMT and NQO1 are key deactivating enzymes. In this initial study, we examined whether the expression of these four critical estrogen activating/deactivating enzymes is altered in breast cancer. Control breast tissue was obtained from four women who underwent reduction mammoplasty. Breast tissues from five women with breast carcinoma, who underwent mastectomy, were used as cases. The level of expression of CYP19, CYP1B1, COMT and NQO1 mRNAs was quantified from total RNA using a real time RT-PCR method in an ABI PRISM 7700 sequence detection system. The control breast tissues showed lower expression of the activating enzymes, CYP19 and CYP1B1, and higher expression of the deactivating enzymes, COMT and NQO1, compared to the cases. In the cases, the reverse pattern was observed: greater expression of activating enzymes and lower expression of deactivating enzymes. Thus, in women with breast cancer, estrogen metabolism may be related to altered expression of multiple genes. These unbalances appear to be instrumental in causing excessive formation of catechol estrogen quinones that, by reacting with DNA, initiate the series of events leading to breast cancer. 相似文献
78.
Extracting a comprehensive overview from the huge amount of information arising from whole-genome analyses is a significant challenge. This review critically surveys the state of the art methods that are used to connect information from functional genomic studies to biological function. Cluster analysis methods for inferring the correlation between genes are discussed, as are the methods for integrating gene expression information with existing information on biological pathways and the methods that combine cluster analysis with biological information to reconstruct novel biological networks. 相似文献
79.
Metabolism and DNA binding studies of 4-hydroxyestradiol and estradiol-3,4-quinone in vitro and in female ACI rat mammary gland in vivo 总被引:3,自引:0,他引:3
Li KM Todorovic R Devanesan P Higginbotham S Köfeler H Ramanathan R Gross ML Rogan EG Cavalieri EL 《Carcinogenesis》2004,25(2):289-297
Studies of estrogen metabolism, formation of DNA adducts, carcinogenicity, cell transformation and mutagenicity have led to the hypothesis that reaction of certain estrogen metabolites, predominantly catechol estrogen-3,4-quinones, with DNA can generate the critical mutations initiating breast, prostate and other cancers. The endogenous estrogens estrone (E1) and estradiol (E2) are oxidized to catechol estrogens (CE), 2- and 4-hydroxylated estrogens, which can be further oxidized to CE quinones. To determine possible DNA adducts of E1(E2)-3,4-quinones [E1(E2)-3,4-Q], we reported previously that the reaction of E1(E2)-3,4-Q with dG produces the depurinating adduct 4-hydroxyE1(E2)-1-N7Gua [4-OHE1(E2)-1-N7Gua] by 1,4-Michael addition (Stack et al., Chem. Res. Toxicol., 1996, 9, 851). We report here that reaction of E1(E2)-3,4-Q with Ade results in the formation of 4-OHE1(E2)-1-N3Ade by 1,4-Michael addition. The N7Gua and N3Ade depurinating adducts formed both in vitro and in rat mammary gland in vivo were analyzed by HPLC with electrochemical detection and, for some samples, by LC/MS/MS. When E2-3,4-Q was reacted with DNA in vitro, the depurinating adducts 4-OHE1(E2)-1-N3Ade and 4-OHE1(E2)-1-N7Gua, which are rapidly lost from DNA by cleavage of the glycosyl bond, were formed (>99% of the total adducts), as well as traces of stable adducts, which remain in DNA unless removed by repair. Similar results were obtained when 4-OHE2 was oxidized by horseradish peroxidase, lactoperoxidase, tyrosinase or phenobarbital-induced rat liver microsomes in the presence of DNA. When 4-OHE2 or E2-3,4-Q was injected into the mammary glands of female ACI rats in vivo and the mammary tissue was excised 1 h later, the depurinating adducts 4-OHE2-1-N3Ade and 4-OHE2-1-N7Gua constituted >99% of the total adducts formed. In addition, 4-OHE2 conjugates formed by reaction of E2-3,4-Q with glutathione were also detected. These results demonstrate that the 4-CE are metabolized to CE-3,4-Q, which react with DNA to form primarily depurinating adducts. These adducts can generate the critical mutations that initiate cancer (Chakravarti et al., Oncogene, 2001, 20, 7945; Chakravarti et al., Proc. Am. Assoc. Cancer Res., 2003, 44, 180). 相似文献