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At least 1,063 records · Page 59Linked to original sources
PubMed1992

Tumour oestrogen receptor content allows selection of elderly patients with breast cancer for conservative tamoxifen treatment.

Immunocytochemical analysis was used to determine tumour oestrogen receptor (ER) content in elderly patients with primary operable breast cancer. Only those ER positive were selected for conservative treatment with tamoxifen alone. Initial response was compared with that of historical controls not selected according to ER status. Early progressive disease was markedly reduced at 6 months, from 30 per cent in the unselected control group to 2 per cent in the study group (P < 0.001). Immunocytochemical analysis is useful for the initial selection of elderly patients with breast cancer who may be treated with tamoxifen alone.

Aged↗
PubMed2006

Molecular and biochemical analysis of rainbow trout LCK suggests a conserved mechanism for T-cell signaling in gnathostomes.

Two genes were identified in rainbow trout that display high sequence identity to vertebrate Lck. Both of the trout Lck transcripts are associated with lymphoid tissues and were found to be highly expressed in IgM-negative lymphocytes. In vitro analysis of trout lymphocytes indicates that trout Lck mRNA is up-regulated by T-cell mitogens, supporting an evolutionarily conserved function for Lck in the signaling pathways of T-lymphocytes. Here, we describe the generation and characterization of a specific monoclonal antibody raised against the N-terminal domains of recombinant trout Lck that can recognize Lck protein(s) from trout thymocyte lysates that are similar in size ( approximately 57kDa) to mammalian Lck. This antibody also reacted with permeabilized lymphocytes during FACS analysis, indicating its potential usage for cellular analyses of trout lymphocytes, thus representing an important tool for investigations of salmonid T-cell function.

Amino Acid Sequence↗
PubMed2006

Is lobular carcinoma in situ as a component of breast carcinoma a risk factor for local failure after breast-conserving therapy? Results of a matched pair analysis.

BACKGROUND: The goals of the current study were to compare the clinicopathologic presentations of patients with lobular carcinoma in situ (LCIS) as a component of breast carcinoma who were treated with breast conserving surgery (BCS) and radiation therapy (RT) with those of patients without LCIS as part of their primary tumor and to report rates of local control by overall cohort and specifically in patients with positive margins for LCIS and multifocal LCIS. METHODS: Sixty-four patients with Stages 0-II breast carcinoma with LCIS (LCIS-containing tumor group, LCTG) that had received BCS+RT treatment at the University of Michigan between 1989 and 2003 were identified. These patients were matched to 121 patients without LCIS (control group) in a 1:2 ratio. RESULTS: The median follow-up time was 3.9 years (range, 0.3-18.9 yrs). There were no significant differences between the two groups with regard to clinical, pathologic, or treatment-related variables or in mammographic presentation, with the exception of a higher proportion of the LCTG patients who received adjuvant hormonal therapy (P = 0.01). The rates of local control at 5 years were 100% in the LCTG group and 99.1% in the control group (P = 0.86). The presence of LCIS at the margins and the size and presence of multifocal LCIS did not alter the rate of local control. CONCLUSIONS: The extent of LCIS and its presence at the margins did not reduce the excellent rates of local control after BCS+RT. The data suggest that LCIS in the tumor specimen, even when multifocal, should not affect selection of patients for BCS and whole-breast RT.

Adult↗
PubMed1999

Functional genomics in Caenorhabditis elegans: An approach involving comparisons of sequences from related nematodes.

Comparative genomic analysis was used to investigate the gene structure of the bli-4 locus from two related Caenorhabditis species, C. elegans and C. briggsae. In C. elegans, bli-4 is a complex gene encoding a member of the kex2/subtilisin-like family of proprotein convertases. Genomic sequence comparisons coupled with RT-PCR analysis identified five additional coding exons that had not been identified previously using standard recombinant DNA techniques. The C. briggsae gene was able to rescue both viable blistered and developmentally arrested mutants of C. elegans bli-4, demonstrating functional conservation. In addition, deletion analysis of conserved sequences outside of coding regions, combined with phenotypic rescue experiments, identified regulatory elements that alter the expression of the bli-4 gene. These results demonstrate the utility of genomic sequence comparisons of homologous genes in related species as an effective tool with which to dissect the functional information of complex genes.

Alternative Splicing↗
PubMed1995

Conserved gene sequences for species identification: PCR analysis of the 3' UTR of the SON gene distinguishes human and other mammalian DNAs.

In this paper we show that the polymerase chain reaction (PCR) can be used on regions of highly conserved genes, such as the 3' untranslated region (3' UTR) of the SON gene, to identify the mammalian origin of a sample. Using this test, we have been able to distinguish human, monkey, cat, dog, mouse and hamster DNAs. We have also determined the DNA sequence of these different PCR products, which can be used to reinforce species identification. The advantages of this test are that: (i) no prior information is required on the possible species origin of a sample, (ii) the reaction produces a single PCR product which varies in size according to the species of origin, making the test simple to interpret, and (iii) the target region of DNA amplified in these experiments is small and can easily be sequenced and sized using automated techniques. This small size has enabled us to successfully amplify this product from DNA extracted from compromised material (human bone samples) and so demonstrate that the test is valuable for the characterisation of remains in which DNA is degraded.

Animals↗
PubMed2005

Minimizing local recurrence after breast conserving therapy using intraoperative shaved margins to determine pathologic tumor clearance.

BACKGROUND: This study analyzed survival, locoregional recurrence, and reexcision rates after breast conserving therapy, based on the margin analysis technique used at the University of Florida, which incorporates frozen section analysis of shaved breast tissue from the lumpectomy cavity. STUDY DESIGN: A retrospective review was done of 257 patients who underwent 267 consecutive lumpectomy operations and completed radiation therapy at our institution. Margins in 189 patients were assessed using frozen section analysis of shaved margins from the lumpectomy cavity. RESULTS: Breast conserving therapy was performed for 220 (83%) patients with early breast cancer (T1 and T2 tumors) and 47 (17%) with ductal carcinoma in situ. With a median followup of 5.6 years, the crude locoregional recurrence rates for patients who had margins analyzed intraoperatively by frozen section analysis or margins analyzed by permanent analysis were 1.9% (3 of 157) and 3.1% (2 of 63), respectively, for early breast cancer and 15.6% (5 of 32) and 6.6% (1 of 15) for ductal carcinoma in situ (p=NS). Survival rates were 97% and 78%, at 5 and 10 years, respectively, for the early breast cancer patients, and 98% and 98%, respectively, for ductal carcinoma in situ patients. Permanent intraoperative frozen section analysis reexcision rates were 33.3% (26 of 78) and 5.8% (11 of 189). CONCLUSIONS: Regardless of the technique used for margin analysis, breast conserving therapy led to low locoregional recurrence relative to national figures, pointing to the importance of the technique of radiation therapy at our institution. Reexcision rate was reduced with the use of frozen section analysis.

Adult↗
PubMed2001

Sex chromosomes and sex-determining genes: insights from marsupials and monotremes.

Comparative studies of the genes involved in sex determination in the three extant classes of mammals, and other vertebrates, has allowed us to identify genes that are highly conserved in vertebrate sex determination and those that have recently evolved roles in one lineage. Analysis of the conservation and function of candidate sex determining genes in marsupials and monotremes has been crucial to our understanding of their function and positioning in a conserved mammalian sex-determining pathway, as well as their evolution. Here we review comparisons between genes in the sex-determining pathway in different vertebrates, and ask how these comparisons affect our views on the role of each gene in vertebrate sex determination.

Animals↗
PubMed1999

Sex chromosomes and sex-determining genes: insights from marsupials and monotremes.

Comparative studies of the genes involved in sex determination in the three extant classes of mammals, and other vertebrates, has allowed us to identify genes that are highly conserved in vertebrate sex determination and those that have recently evolved roles in one lineage. Analysis of the conservation and function of candidate genes in different vertebrate groups has been crucial to our understanding of their function and positioning in a conserved vertebrate sex-determining pathway. Here we review comparisons between genes in the sex-determining pathway in different vertebrates, and ask how these comparisons affect our views on the role of each gene in vertebrate sex determination.

Animals↗
PubMed1995

Association between cigarette smoking and mutation of the p53 gene in squamous-cell carcinoma of the head and neck.

BACKGROUND: Although epidemiologic studies have long associated tobacco and alcohol use with the development of squamous-cell carcinoma of the head and neck, the molecular targets of these carcinogens have yet to be identified. We performed a molecular analysis to determine the pattern of mutations in the p53 gene in neoplasms from patients with squamous-cell carcinoma of the head and neck and a history of tobacco or alcohol use. METHODS: Sequence analysis of the conserved regions of the p53 gene was performed in tumor samples from 129 patients with primary squamous-cell carcinoma of the head and neck. We then used statistical analysis to identify any patient characteristics associated with mutation of the p53 gene. RESULTS: We found p53 mutations in 42 percent of the patients (54 of 129). Fifty-eight percent of the patients who smoked cigarettes and used alcohol (37 of 64; 95 percent confidence interval, 45 to 70 percent), 33 percent of the patients who smoked but abstained from alcohol (13 of 39; 95 percent confidence interval, 19 to 50 percent), and 17 percent of the patients who neither smoked nor drank alcohol (4 of 24, 95 percent confidence interval, 5 to 37 percent) had p53 mutations (P = 0.001). (Two patients used alcohol but did not smoke, and neither had a p53 mutation.) Furthermore, 100 percent of the mutations in the patients who neither drank nor smoked occurred at sites containing cytidine phosphate guanosine dinucleotides (potentially representing endogenous mutations) within the p53 gene (5 of 5 mutations; 95 percent confidence interval, 48 to 100 percent), whereas only 23 percent of those in cigarette smokers consisted of such changes (12 of 53 mutations; 95 percent confidence interval, 12 to 36 percent; P = 0.001). CONCLUSIONS: In our study, a history of tobacco and alcohol use was associated with a high frequency of p53 mutations in patients with squamous-cell carcinoma of the head and neck. Preliminary evidence linked cigarette smoking to p53 mutations at nonendogenous mutation sites. Our findings suggest a role for tobacco in the molecular progression of squamous-cell carcinoma of the head and neck and support the epidemiologic evidence that abstinence from smoking is important to prevent head and neck cancer.

Base Composition↗
PubMed2005

A conserved element in Myc that negatively regulates its proapoptotic activity.

Myc is an oncoprotein transcription factor that promotes cell proliferation and apoptosis. Analysis of highly conserved elements within vertebrate Myc proteins has been instrumental in defining the functions of the Myc protein. Here, we probe the role of a highly conserved, but little studied, element within the central region of c-Myc, termed 'Myc box III' (MbIII). We show that MbIII is important for transcriptional repression by Myc, and for transformation both in vitro and in a mouse model of lymphomagenesis. Curiously, disruption of MbIII decreases transformation activity by increasing the efficiency with which Myc can induce apoptosis, suggesting that MbIII is a negative regulator of programmed cell death. These findings reveal a role for MbIII in Myc biology, and establish that the oncogenic capacity of Myc is linked directly to its ability to temper the apoptotic response.

Animals↗
PubMed1987

The herpes simplex virus type 1 DNA polymerase gene: site of phosphonoacetic acid resistance mutation in strain Angelotti is highly conserved.

By comparative sequence analysis of the herpes simplex virus type 1 DNA polymerase gene of strain Angelotti and a phosphonoacetic acid-resistant (PAAr) derivative, the site of the PAAr mutation was identified as a single nucleotide (C----T) conversion within the mapping limits of the known PAAr mutations of strains KOS and 17. The conservative amino acid change at residue 719 from alanine to valine results in a radical change in the properties of the polymerase, rendering the mutant enzyme resistant to PAA and various antiviral compounds. Amino acid homologies as well as secondary structure analysis reveal that the PAAr mutation is contained in a 14 amino acid sequence which is highly conserved, and detected in the central domain of prokaryotic and eukaryotic DNA polymerases.

Amino Acid Sequence↗
PubMed2006

Distant regulatory elements in a Sox10-beta GEO BAC transgene are required for expression of Sox10 in the enteric nervous system and other neural crest-derived tissues.

Sox10 is an essential transcription factor required for development of neural crest-derived melanocytes, peripheral glia, and enteric ganglia. Multiple transcriptional targets regulated by Sox10 have been identified; however, little is known regarding regulation of Sox10. High sequence conservation surrounding 5' exons 1 through 3 suggests these regions might contain functional regulatory elements. However, we observed that these Sox10 genomic sequences do not confer appropriate cell-specific transcription in vitro when linked to a heterologous reporter. To identify elements required for expression of Sox10 in vivo, we modified bacterial artificial chromosomes (BACs) to generate a Sox10betaGeoBAC transgene. Our approach leaves endogenous Sox10 loci unaltered, circumventing haploinsufficiency issues that arise from gene targeting. Sox10betaGeoBAC expression closely approximates Sox10 expression in vivo, resulting in expression in anterior dorsal neural tube at embryonic day (E) 8.5 and in cranial ganglia, otic vesicle, and developing dorsal root ganglia at E10.5. Characterization of Sox10betaGeoBAC expression confirms the presence of essential regulatory regions and additionally identifies previously unreported expression in thyroid parafollicular cells, thymus, salivary, adrenal, and lacrimal glands. Fortuitous deletions in independent Sox10betaGeoBAC lines result in loss of transgene expression in peripheral nervous system lineages and coincide with evolutionarily conserved regions. Our analysis indicates that Sox10 expression requires the presence of distant cis-acting regulatory elements. The Sox10betaGeoBAC transgene offers one avenue for specifically testing the role of individual conserved regions in regulation of Sox10 and makes possible analysis of Sox10+ derivatives in the context of normal neural crest development.

5' Flanking Region↗
PubMed2006

Characterization of retinoid-X receptor genes rxra, rxrba, rxrbb and rxrg during zebrafish development.

During development of vertebrate embryos, retinoic acid plays a variety of roles that are mediated by binding to retinoic acid receptors (Rars) and their heterodimerization partners, the retinoid receptors (Rxrs). Here, we characterize the expression patterns of four zebrafish rxr genes during development and provide an analysis of the phylogenetic relationships between zebrafish and tetrapod Rxr genes based on sequence similarities and conserved syntenies. This analysis prompted the renaming of several of the zebrafish rxr genes to match their tetrapod orthologs. Understanding phylogenetic relationships among Rxr genes and their expression patterns during development provides a foundation for future studies of Rxr functions.

Animals↗
PubMed1999

Mutational analysis of subunit i beta2 (MECL-1) demonstrates conservation of cleavage specificity between yeast and mammalian proteasomes.

Proteasomes are the major protein-degrading complexes in the cytosol and regulate many cellular processes. To examine the functional importance of the MC14/MECL-1 proteasome active site subunits, cell lines expressing a catalytically inactive form of MECL-1 were established. Whereas mutant MECL-1 was readily incorporated into cytosolic proteasomes, replacing the constitutive MC14 subunit, removal of the prosequence was incomplete indicating that its processing required autocatalytic cleavage. Functional analyses showed that the absence of the MC14/MECL-1 active sites abrogated proteasomal trypsin-like activity, but did not affect other catalytic activities. Our data demonstrate a conservation of cleavage specificity between mammalian and yeast proteasomes.

Amino Acid Sequence↗
PubMedDate not supplied

[Analysis of own clinical material treated by conservative and aggressive control of intracranial hypertension].

These problems arising during the treatment of increased intracranial pressure (ICP) were analysed on the basis of own clinical material with consideration of different therapeutic methods--pharmacological and aggressive. Statistical analysis (contingency tables) showed that the treatment consisting of dexamethason, mannitol and furosemid was the most efficient in the group of patient with increased ICP in the range 15-30 mmHg. In patients with ICP in the range 30-50 mmHg, where other aggressive methods of treatment had failed, the most efficient treatment was cranio-dural decompression.

Dexamethasone↗
PubMed1995

Self peptides bound by HLA class I molecules are derived from highly conserved regions of a set of evolutionarily conserved proteins.

An evolutionary analysis of self peptides reported to be bound by HLA class I molecules showed that these peptides are largely derived from proteins that have been highly conserved in the history of mammals. These proteins also often have universal tissue expression and have a higher than average frequency of highly hydrophilic residues. The peptides themselves are generally still more highly conserved than the source proteins and have a higher frequency of highly hydrophobic residues, evidently often being derived from conserved hydrophobic cores of the source proteins. These results suggest that the mechanism by which peptides are derived for MHC presentation may preferentially select peptides from conserved protein regions. In the case of parasite-derived peptides, such a mechanism would be adaptive in that it would reduce the likelihood of escape mutants.

Animals↗
PubMed1995

Structure-function analysis of Bcl-2 protein. Identification of conserved domains important for homodimerization with Bcl-2 and heterodimerization with Bax.

The Bcl-2 protein is a suppressor of programmed cell death that homodimerizes with itself and forms heterodimers with a homologous protein Bax, a promoter of cell death. Expression of Bax in Saccharomyces cerevisiae as a membrane-bound fusion protein results in a lethal phenotype that is suppressible by co-expression of Bcl-2. Functional analysis of deletion mutants of human Bcl-2 in yeast demonstrated the presence of at least three conserved domains that are required to suppress Bax-mediated cytotoxicity, termed domains A (amino acids 11-33), B (amino acids 138-154), and C (amino acids 188-196). In vitro binding experiments using GST-Bcl-2 fusion proteins demonstrated that Bcl-2(delta B) and Bcl-2(delta C) deletion mutants had a markedly impaired ability to heterodimerize with Bax but retained the ability to homodimerize with wild-type Bcl-2. In contrast, Bcl-2(delta A) and an NH2-terminal deletion mutant Bcl-2(delta 1-82) retained Bax binding activity in vitro but failed to suppress Bax-mediated cytotoxicity in yeast. Sequences downstream of domain C in the region 197-218 also were shown to be required for Bax-binding in vitro and anti-death function in yeast. Analysis of Bcl-2/Bcl-2 homodimerization using both in vitro binding assays as well as a yeast two-hybrid method provided evidence in support of a head-to-tail model for Bcl-2/Bcl-2 homodimerization and revealed that sequences within the NH2-terminal A domain interact with a structure that requires the presence of both the carboxyl B and C domains in combination. In addition to further delineating structural features within Bcl-2 that are required for homo-dimerization, the findings reported here support the hypothesis that Bcl-2 promotes cell survival by binding directly to Bax but suggest that ability to bind Bax can be insufficient for anti-cell death function.

Amino Acid Sequence↗
PubMed2005

Improved K-means clustering algorithm for exploring local protein sequence motifs representing common structural property.

Information about local protein sequence motifs is very important to the analysis of biologically significant conserved regions of protein sequences. These conserved regions can potentially determine the diverse conformation and activities of proteins. In this work, recurring sequence motifs of proteins are explored with an improved K-means clustering algorithm on a new dataset. The structural similarity of these recurring sequence clusters to produce sequence motifs is studied in order to evaluate the relationship between sequence motifs and their structures. To the best of our knowledge, the dataset used by our research is the most updated dataset among similar studies for sequence motifs. A new greedy initialization method for the K-means algorithm is proposed to improve traditional K-means clustering techniques. The new initialization method tries to choose suitable initial points, which are well separated and have the potential to form high-quality clusters. Our experiments indicate that the improved K-means algorithm satisfactorily increases the percentage of sequence segments belonging to clusters with high structural similarity. Careful comparison of sequence motifs obtained by the improved and traditional algorithms also suggests that the improved K-means clustering algorithm may discover some relatively weak and subtle sequence motifs, which are undetectable by the traditional K-means algorithms. Many biochemical tests reported in the literature show that these sequence motifs are biologically meaningful. Experimental results also indicate that the improved K-means algorithm generates more detailed sequence motifs representing common structures than previous research. Furthermore, these motifs are universally conserved sequence patterns across protein families, overcoming some weak points of other popular sequence motifs. The satisfactory result of the experiment suggests that this new K-means algorithm may be applied to other areas of bioinformatics research in order to explore the underlying relationships between data samples more effectively.

Algorithms↗