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61.
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Summary Soils derived from hydrothermally altered andesite support unique communities of Sierran conifers (Pinus ponderosa Laws. and P. jeffreyi Grev. and Balf.) amongst sagebrush (Artemisia tridentata Nutt.) vegetation in the western Great Basin. Plants grown in soil derived from hydrothermally altered bedrock had lower growth rates, total biomass, and net photosynthetic rates than plants grown in soil derived from unaltered andesite of the same formation. Total dry mass was 10 to 28% lower for conifers grown in altered soil whereas dry mass of Artemisia tridentata and Bromus tectorum L. was reduced by over 90%. Results from a nutrient amendment experiment indicated that low phosphorus was the dominant limitation in altered soil, and phosphorus-deficiency affected growth primarily by limiting leaf area development rather than direct inhibition of photosynthesis. The proportionately greater reduction of biomass for Artemisia and Bromus grown in altered soil supports our hypothesis that Great Basin vegetation is excluded from altered soil by intolerance to nutrient deficiency. The Sierran conifers growing on this rock type are therefore free of competition for water with Great Basin vegetation and are able to persist in an exceptionally dry climate.  相似文献   
63.
Depletion of cellular GSH by diethyl maleate (DEM) potentiates CH2O toxicity in isolated rat hepatocytes and it was postulated that this increase in toxicity is due to the further decrease in GSH caused by CH2O in DEM-pretreated hepatocytes (1). The present investigation was conducted to investigate further the effects of CH2O, DEM, and acrolein (a compound which is structurally related to CH2O and DEM) on subcellular GSH pools and on protein sulfhydryl groups (PSH). CH2O caused a decrease in cytosolic GSH but had no effect on mitochondrial GSH either in previously untreated hepatocytes or in DEM-pretreated hepatocytes in which GSH was approximately 25% of control. DEM decreased both cytosolic and mitochondrial GSH but it did not produce toxicity. Neither CH2O (up to 7.5 mM) nor DEM (20 mM) decreased PSH. However, in cells pretreated with 1 mM DEM, CH2O (7.5 mM) decreased PSH and this effect preceded cell death. Acrolein decreased both cytosolic and mitochondrial GSH and it also decreased PSH significantly prior to causing cell death. CH2O and acrolein stimulated phosphorylase alpha activity, indicative of an increase in cytosolic free Ca2+, by a PSH-independent and PSH-dependent mechanism, respectively. These results suggest that the further depletion of cellular GSH by CH2O in DEM-pretreated cells is not due to the depletion of mitochondrial GSH. CH2O toxicity in DEM-pretreated cells is, however, correlated with depletion of PSH. The critical sulfhydryl protein(s) responsible for cell death remain to be more clearly defined.  相似文献   
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cis-Diamminedichloroplatinum (II) (cisplatin, CDDP) is a widely used chemotherapeutic agent. While many tumors are highly responsive to CDDP, certain tumors are resistant to this drug, limiting its efficacy. The anti-tumor activity of CDDP is believed to result from its coordination bonding to chromosomal DNA. Alterations in tumor cell sensitivity to CDDP may result from the presence or absence of protein(s) which specifically recognize CDDP-damaged DNA. We have developed a damaged-DNA affinity precipitation assay that allows the direct identification of cellular proteins that bind to CDDP-damaged DNA. Using this procedure, we have identified several proteins which specifically bind to CDDP-damaged DNA. Two of these proteins have been identified as high mobility group proteins (HMG) 1 and 2 in the current report, we have characterized the binding of these proteins to CDDP-DNA. The calculated Kd of binding to CDDP-damaged DNA was 3.27 x 10(-10) for HMG1 and 1.87 x 10(-10) for HMG2. Using highly specific chemical modifying reagents, we have determined that Cys residues play an important role in protein binding. We also observed that HMG2 will bind to DNA modified with carboplatin and iproplatin although to a lesser extent than to DNA damaged with CDDP. Thus, our results indicate that HMG 2 binds with high affinity to DNA modified with therapeutically active platinum compounds. In addition, our findings suggest that thiol groups play an essential role in the binding of HMG1 and HMG2 to CDDP-DNA.  相似文献   
66.
Characterization of the La (SS-B) antigen from several mammalian sources   总被引:6,自引:0,他引:6  
The La or SS-B antigen is associated with rheumatic diseases, systemic lupus erythematosus, and Sjogren's syndrome, and is part of a larger ribonucleoprotein complex. Immunoaffinity chromatography allowed for the efficient separation of the La antigen from the bulk of the cellular proteins, with a minimum of protease exposure. Protein blot analysis of the affinity-isolated material indicated a major immunoreactive polypeptide of 50,000 m.w. A comparison of this antigen in a number of mammalian sources (human, rabbit, and rat) suggested strong conservation of the native polypeptide m.w. Likewise, in a direct comparison of this antigen from Epstein-Barr virus-infected cells in which there are distinct differences in the antigen-associated RNA species, the immunoreactive polypeptide species were of similar size. The La protein is readily susceptible to endogenous proteolysis, with the resulting generation of smaller, discrete polypeptides that still retain antigenicity. By using the La protein to monitor potential degradation, we have developed a simple two-step procedure to isolate the La-associated snRNP complex. The complexes thus isolated provide material suitable as a source of both the active antigen and of the functional ribonucleoprotein complex.  相似文献   
67.
We have previously demonstrated that the EP1 subtype of PGE2 receptor is expressed in the differentiated compartment of normal human epidermis and is coupled to intracellular calcium mobilization. We therefore hypothesized that the EP1 receptor is coupled to keratinocyte differentiation. In in vitro studies, radioligand binding, RT-PCR, immunoblot and receptor agonist-induced second messenger studies demonstrate that the EP1 receptor is up-regulated by high cell density in human keratinocytes and this up-regulation precedes corneocyte formation. Moreover, two different EP1 receptor antagonists, SC51322 and AH6809, both inhibited corneocyte formation. SC51322 also inhibited the induction of differentiation-specific proteins, cytokeratin K10 and epidermal transglutaminase. We next examined the immunolocalization of the EP1 receptor in non-melanoma skin cancer in humans. Well-differentiated SCCs exhibited significantly greater membrane staining, while spindle cell carcinomas and BCCs had significantly decreased membrane staining compared with normal epidermis. This data supports a role for the EP1 receptor in regulating keratinocyte differentiation.  相似文献   
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69.

Introduction

Male breast cancer (MBC) is a rare, yet potentially aggressive disease. Although literature regarding female breast cancer (FBC) is extensive, little is known about the etiopathogenesis of male breast cancer. Studies from our laboratory show that MBCs have a distinct immunophenotypic profile, suggesting that the etiopathogenesis of MBC is different from FBCs. The aim of this study was to evaluate and correlate the immunohistochemical expression of cell cycle proteins in male breast carcinoma to significant clinico-biological endpoints.

Methods

75 cases of MBC were identified using the records of the Saskatchewan Cancer Agency over 26 years (1970-1996). Cases were reviewed and analyzed for the immunohistochemical expression of PCNA, Ki67, p27, p16, p57, p21, cyclin-D1 and c-myc and correlated to clinico-biological endpoints of tumor size, node status, stage of the disease, and disease free survival (DFS).

Results

Decreased DFS was observed in the majority of tumors that overexpressed PCNA (98%, p = 0.004). The overexpression of PCNA was inversely correlated to the expression of Ki67 which was predominantly negative (78.3%). Cyclin D1 was overexpressed in 83.7% of cases. Cyclin D1 positive tumors were smaller than 2 cm (55.6%, p = 0.005), had a low incidence of lymph node metastasis (38.2%, p = 0.04) and were associated with increased DFS of >150 months (p = 0.04). Overexpression of c-myc (90%) was linked with a higher incidence of node negativity (58.3%, p = 0.006) and increased DFS (p = 0.04). p27 over expression was associated with decreased lymph node metastasis (p = 0.04). P21 and p57 positive tumors were related to decreased DFS (p = 0.04). Though p16 was overexpressed in 76.6%, this did not reach statistical significance with DFS (p = 0.06) or nodal status (p = 0.07).

Conclusion

Aberrant cell cycle protein expression supports our view that these are important pathways involved in the etiopathogenesis of MBC. Tumors with overexpression of Cyclin D1 and c-myc had better outcomes, in contrast to tumors with overexpression of p21, p57, and PCNA with significantly worse outcomes. P27 appears to be a predictive marker for lymph nodal status. Such observation strongly suggests that dysregulation of cell cycle proteins may play a unique role in the initiation and progression of disease in male breast cancer. Such findings open up new avenues for the treatment of MBC as a suitable candidate for novel CDK-based anticancer therapies in the future.  相似文献   
70.
The success of high resolution genetic mapping of disease predisposition and quantitative trait loci in humans and experimental animals depends on the positions of key crossover events around the gene of interest. In mammals, the majority of recombination occurs at highly delimited 1-2 kb long sites known as recombination hotspots, whose locations and activities are distributed unevenly along the chromosomes and are tightly regulated in a sex specific manner. The factors determining the location of hotspots started to emerge with the finding of PRDM9 as a major hotspot regulator in mammals, however, additional factors modulating hotspot activity and sex specificity are yet to be defined. To address this limitation, we have collected and mapped the locations of 4829 crossover events occurring on mouse chromosome 11 in 5858 meioses of male and female reciprocal F1 hybrids of C57BL/6J and CAST/EiJ mice. This chromosome was chosen for its medium size and high gene density and provided a comparison with our previous analysis of recombination on the longest mouse chromosome 1. Crossovers were mapped to an average resolution of 127 kb, and thirteen hotspots were mapped to <8 kb. Most crossovers occurred in a small number of the most active hotspots. Females had higher recombination rate than males as a consequence of differences in crossover interference and regional variation of sex specific rates along the chromosome. Comparison with chromosome 1 showed that recombination events tend to be positioned in similar fashion along the centromere-telomere axis but independently of the local gene density. It appears that mammalian recombination is regulated on at least three levels, chromosome-wide, regional, and at individual hotspots, and these regulation levels are influenced by sex and genetic background but not by gene content.  相似文献   
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