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31.
RM Whyatt DA Bell W Jedrychowski RM Santella SJ Garte G Cosma DK Manchester TL Young TB Cooper R Ottman FP Perera 《Canadian Metallurgical Quarterly》1998,19(8):1389-1392
This study investigated the relationship in human placenta between polycyclic aromatic hydrocabon (PAH)-DNA adduct levels and two biomarkers of cytochrome P4501A1 (CYP1A1): gene induction evidenced by CYP1A1 mRNA, and a genetic polymorphism, the CYP1A1 MspI RFLP. CYP1A1 codes for an inducible enzyme system that catalyzes the bioactivation of PAHs. Prior research found a high correlation in human lung tissue between CYP1A1 activity and DNA damage from PAHs. The CYP1A1 Mspi RFLP has been linked in some studies to risk of lung cancer. The relationships in human placenta between DNA damage, CYP1A1 activity and genotype have not been well characterized and may be relevant to risks from transplacental PAH exposure. The study cohort consisted of 70 newborns from Krakow, Poland, a city with elevated air pollution, and 90 newborns from nearby Limanowa, an area with lower air pollution but greater indoor coal use. Contrary to results seen previously in lung tissue, CYP1A1 mRNA was not significantly correlated with PAH-DNA adduct levels in the placenta. Smoking (self-reported maternal and infant plasma cotinine) was significantly associated with CYP1A1 mRNA levels (P < 0.01), but not with PAH-DNA adduct levels. Placental PAH-DNA adduct levels were significantly higher in infants with the CYP1A1 MspI restriction site compared with infants without the restriction site (P < 0.01), implicating a genetic factor in inter-individual variation in DNA damage in human placenta. Further studies are needed to determine the relevance of this finding to risk of transplacental carcinogenesis. 相似文献
32.
J Eben-Brunnen S Reymann LA Awni T Cole T Hellmann KP Hellmann G Paetzold J Kleineke FP Thinnes H G?tz N Hilschmann 《Canadian Metallurgical Quarterly》1998,379(12):1419-1426
Using an established biochemical approach, five subcellular fractions of human B lymphocytes were prepared by differential centrifugation. Crude membranes were passed over a lentil lectin column to enrich carbohydrate-coated cell surface microsomes. The lectin-bound fraction contained a high amount of plasma membrane-derived microsomes as indicated by cell surface markers. All subcellular fractions in Western blots proved to contain distinct but variable amounts of porin. There was a strong increase in porin content from crude membranes to plasma membrane-derived vesicles. The porin content of this fraction appeared to be higher than that of mitochondria. In the final step the plasma membrane-derived microsome fraction proved to be devoid of contamination by outer mitochondrial membranes, as revealed by antibodies against the established markers MAO B and Tom20 applied in Western blots. These data prove the extramitochondrial expression of human type-1 porin/ type-1 VDAC. 相似文献
33.
To determine whether endoplasmic reticulum (ER) proliferation in hepatocytes after phenobarbital (PB) administration relates closely to cytochrome P-450 (P-450) increase, we have measured the amount of total P-450 per unit cytoplasmic volume (P-450 content) by microphotometry and estimated the area of ER per unit cytoplasmic volume (ER area) by morphometry in periportal, midzonal, and perivenular hepatocytes of mice injected daily with PB (100 mg/kg), or with PB (100 mg/kg) plus cobalt chloride (50 mg/kg) for three days. After injection of PB, the P-450 content and ER area increased in hepatocytes of the three sublobular zones. In mice treated with PB plus cobalt chloride, however, the ER area increased, but the P-450 content decreased or remained unchanged in hepatocytes of the three zones. We conclude that cobalt chloride inhibits the increase in total P-450 but has no effect on the proliferation of ER of hepatocytes in mice treated with PB, indicating a dissociation of ER proliferation and P-450 increase after administration of PB. 相似文献
34.
M Mann JH Shelhamer H Masur VJ Gill W Travis D Solomon J Manischewitz F Stock HC Lane FP Ognibene 《Canadian Metallurgical Quarterly》1997,155(5):1723-1728
This study assessed the presence of cytomegalovirus (CMV) in bronchoalveolar lavage (BAL) in three subpopulations of HIV-infected patients and correlated its presence with clinical status during 3 mo of follow-up. Nineteen asymptomatic volunteers, six patients with CMV retinitis, and 46 patients with acute pulmonary symptoms underwent BAL and were assessed for CMV by cytopathology, conventional shell vial cultures, and antigen detection. Transbronchial biopsies were also obtained when possible and evaluated for histopathologic changes of CMV. All patients were followed for approximately 3 mo. Cytomegalovirus was detected in BAL in nine of 19 (47%) asymptomatic volunteers, in all six patients with CMV retinitis, and in 33 of 46 (72%) patients with pulmonary symptoms. Only one symptomatic patient with a positive CMV BAL culture developed clinically significant CMV pulmonary disease; this patient developed disseminated CMV and died. The only other death occurred in a patient with CMV retinitis who developed staphylococcal bacteremia. None of the asymptomatic volunteers or patients with CMV retinitis developed evidence of CMV pneumonia or any other organ disease with CMV. Cytomegalovirus is frequently detected in BAL from HIV-infected patients regardless of their pulmonary symptoms and its presence does not clinically predict significant pulmonary morbidity or mortality in 3 mo of follow-up. 相似文献
35.
PT Wingfield SJ Stahl DR Thomsen FL Homa FP Booy BL Trus AC Steven 《Canadian Metallurgical Quarterly》1997,71(12):8955-8961
VP26 is a 12-kDa capsid protein of herpes simplex virus 1. Although VP26 is dispensable for assembly, the native capsid (a T=16 icosahedron) contains 900 copies: six on each of the 150 hexons of VP5 (149 kDa) but none on the 12 VP5 pentons at its vertices. We have investigated this interaction by expressing VP26 in Escherichia coli and studying the properties of the purified protein in solution and its binding to capsids. Circular dichroism spectroscopy reveals that the conformation of purified VP26 consists mainly of beta-sheets (approximately 80%), with a small alpha-helical component (approximately 15%). Its state of association was determined by analytical ultracentrifugation to be a reversible monomer-dimer equilibrium, with a dissociation constant of approximately 2 x 10(-5) M. Bacterially expressed VP26 binds to capsids in the normal amount, as determined by quantitative sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Cryoelectron microscopy shows that the protein occupies its usual sites on hexons but does not bind to pentons, even when available in 100-fold molar excess. Quasi-equivalence requires that penton VP5 must differ in conformation from hexon VP5: our data show that in mature capsids, this difference is sufficiently pronounced to abrogate its ability to bind VP26. 相似文献
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38.
T Shimada K El-Bayoumy P Upadhyaya TR Sutter FP Guengerich H Yamazaki 《Canadian Metallurgical Quarterly》1997,57(21):4757-4764
The effects of synthetic chemopreventive organoselenium compounds 1,2-, 1,3-, and 1,4-phenylenebis(methylene)selenocyanate (o-, m-, and p-XSC, respectively), benzyl selenocyanate (BSC), and dibenzyl diselenide (DDS) and inorganic sodium selenite on the oxidation of xenobiotics and procarcinogens by human cytochrome P450 (P450 or CYP) enzymes were determined in vitro. Spectral studies showed that BSC and three XSC compounds (but not sodium selenite or DDS) induced type II difference spectrum when added to the suspension of liver microsomes isolated from beta-naphthoflavone-treated rats, with m-XSC being the most potent in inducing spectral interactions with P450 enzymes; m-XSC also produced a type II spectral change with human liver microsomes. o-, m-, and p-XSC inhibited 7-ethoxyresorufin O-deethylation catalyzed by human liver microsomes when added at concentrations below 1 microM levels, but BSC and DDS were less effective. All of these compounds inhibited the oxidation of model substrates for human P450s to varying extents. We studied the effects of these compounds on the activation of procarcinogens by recombinant human CYP1A1, 1A2, and 1B1 enzymes using Salmonella typhimurium NM2009 tester strain for the detection of DNA damage. The three XSCs were found to be very potent inhibitors of metabolic activation of 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole, 2-amino-3,5-dimethylimidazo[4,5-f]quinoline, and 2-aminoanthracene, catalyzed by CYP1A1, 1A2, and 1B1, respectively. The potency of inhibition of m-XSC on CYP1B1-dependent activation of 2-aminoanthracene was compatible to those of alpha-naphthoflavone. These inhibitory actions may, in part, account for the mechanisms responsible for cancer prevention by organoselenium compounds in laboratory animals. 相似文献
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We have determined the free cortisol concentration in serum using either the Amicon MPS-1 ultrafiltration-centrifugation method (I) or equilibrium dialysis (II). If procedure I was used we found that [1,2,6,7-3H]-, and [4-14C]cortisol had a lower affinity than unlabelled cortisol for corticosteroid binding globulin (CBG). The binding affinity (Ka) to three separate CBG-containing samples was 8-18 times lower for [1,2,6,7-3H]cortisol and 30-90 times lower for [4-14C]cortisol, when compared with that of unlabelled cortisol. This difference in affinity to CBG was not observed if method II was used for the free cortisol determinations. The observed isotope effect in method I is not caused by unspecific binding to material such as the Amicon MPS-1 chamber or to impurities in the tracer. We suggest that the centrifugation step during ultrafiltration changed the conformation of CBG, thereby reducing its affinity for labelled cortisol. It is concluded that incorrect results will be obtained if radiolabelled is cortisol used for determining the free cortisol content of plasma with the Amicon MPS-1 device. 相似文献