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Biomedical subjects

S Fogel

Publications and source records attributed to S Fogel.

At least 19 recordsLinked to original sources

[Biometric study of acute-angle-closure glaucoma using Orbscan and echography].

PURPOSE: To study acute-angle-closure glaucoma (AACG) biometry using Orbscan and echography. MATERIAL AND METHODS: We prospectively studied 200 normal eyes of 100 patients (including eyes with ametropia), 50 eyes of 25 patients before peripherial YAG laser iridotomy, 25 phakic eyes of 25 patients with a history of acute-angle-closure glaucoma (AACG) in the fellow eye. Both plane and polynomial modes of reconstruction of the iridocorneal angle measurement were analyzed. Biometric measurements of the three groups were compared. Biometric measurements (i.e., iridocorneal angle, anterior chamber depth, axial length, and lens thickness) and subjective spherical equivalent were correlated with the etiological classification. RESULTS: Age, sex, iridocorneal angle, anterior chamber depth, lens thickness, axial length and subjective spherical equivalent were significantly different in the three groups (p<0.002). The polynomial iridocorneal angle measurement was 43.4 degrees in the normal group, 36.5 degrees in the iridotomy group, and 28.4 degrees in the AACG group (p<0.001). Iridocorneal angle measurement correlated with the other biometric measurements (rs>0.51; p<0.001) and with the etiological classification (rs< or =0.68; p<0.001). The anterior chamber depth measurement obtained by Orbscan or echography was the best parameter for predicting ACCG (rs=0.77; p<0.001). CONCLUSION: The anterior chamber depth and polynimial iridocorneal angle obtained using the Orbscan device appears to be useful in predicting acute-angle-closure glaucoma.

Acute Disease↗

Cost analysis in vitrectomy: monitored anesthesia care and general anesthesia.

A retrospective study was performed to compare differences in hospital charges between monitored anesthesia care with retrobulbar block and general anesthesia among patients having vitrectomy. Of 128 consecutive patients undergoing vitrectomy between July 1996 and July 1997, group 1 received general anesthesia (n = 41), group 2 received monitored care anesthesia with retrobulbar block (n = 59), and 28 patients were eliminated from the study. There were significant differences in anesthesia charges, operating room charges, pharmacy charges, and total hospital charges between groups 1 and 2. Charges associated with monitored care anesthesia with retrobulbar block are 20% less than charges associated with general anesthesia. Fewer patients in group 2 required postoperative intravenous narcotics than in group 1.

Aged↗

The tat protein of HIV-1 induces galectin-3 expression.

Animal lectins play important roles in a variety of biological processes via their recognition of glycoconjugates. Galectin-3 is a beta-galactoside-binding lectin whose expression is associated with various pathological processes including human T lymphotropic virus (HTLV)-I-infection of human T cell lines and human immunodeficiency virus (HIV) infection of T-lymphoblastic Molt-3 cell line. In the case of HIV-infected cells, it has been suggested that the increase in galectin-3 expression could be related to the expression of the viral regulatory gene tat. These results prompt us to perform more extensive analyses of the relationship between galectin-3 and HIV-1 Tat expressions. In this study, we found that Tat protein expression induces an upregulation of galectin-3 in several human cell lines. In co-transfection experiments, the 5'-regulatory sequences of the galectin-3 gene were significantly upregulated by expression vectors encoding the Tat protein. Analysis performed with 5'-regulatory deleted sequences suggested that galectin-3 induction by Tat is dependent on activation of the Sp-1 binding transcription factor.

Animals↗

The effect of patient-focused redesign on midlevel nurse managers' role responsibilities and work environment.

OBJECTIVE: The authors determine the effect of patient-focused redesign on midlevel nurse managers' role responsibilities and perceptions of work environment. BACKGROUND: Patient-focused redesign models have been initiated in a number of hospitals over the past 10 years. Few studies of the impact of these models on nurse leaders' roles and work responsibilities have been conducted. METHODS: Nine midlevel nurse managers were interviewed about their redesigned leadership roles and the challenges they experienced in implementing patient-focused redesign. RESULTS: Several themes emerged from the data. These themes focused on role change, ambiguity, position power, and environmental uncertainty and turbulence. Each of the nurse managers described feelings of frustration, disconnectedness, and inadequacy and spoke of how difficult it was to be the central figure in the eye of the storm. They noted that previously successful administrative strategies were not producing the same effect as in the past. CONCLUSION: This study provides beginning information about the magnitude of the impact of organizational redesign on midlevel nurse managers. Midlevel managers in this study struggled to keep up with the demands of the change and their own recognition of the importance of remaining committed to the uncertain goals of the institution. They were frustrated by their perceived inability to fix the situation and to meet the multiple needs of the staff. Nonetheless, they supported senior executives and attempted reasonable solutions to the problem.

Humans↗

The early HPV16 proteins can regulate mRNA levels of cell cycle genes in human cervical carcinoma cells by p53-independent mechanisms.

Cervical carcinoma-associated human papillomavirus type 16 (HPV16) encodes E6 and E7 oncoproteins which inactivate p53 and Rb, respectively, but these interactions are not sufficient to account for the oncogenic potential of the virus. Several viral promoters were shown to be regulated by E6 and E7. To identify genes as cellular targets of the HPV16 early proteins, we transfected a new HPV-negative and p53-mutated cervical carcinoma-derived cell line with either the HPV16 full-length genome or the HPV16 E6 gene. HPV16 clones but not 16E6 clones showed a decreased doubling time that was not related to the viral DNA and mRNA patterns. In exponentially growing cells as well as in cells synchronized by serum starvation, expression of the E6 gene was associated with upregulation of the c-fos and c-jun proto-oncogenes and with downregulation of the c-Ha-ras gene. Furthermore, a viral gene other than E6 may be involved in downregulation of p53 because a reduced mRNA level at the G1/S transition was observed only in HPV16-cells. The present study on natural host cells indicates p53-independent transcriptional modulations of cell cycle regulatory genes related to HPV16 E6 and E7 expression.

DNA, Viral↗

Biodegradation of [(sup14)C]Benzo[a]pyrene Added in Crude Oil to Uncontaminated Soil.

To investigate the possible cometabolic biodegradation of benzo[a]pyrene (BaP), crude oil spiked with [7-(sup14)C]BaP and unlabeled BaP was added to soil with no known pollution history, to give 34 g of oil and 67 mg of BaP/kg of dry soil. The oil-soil mixture was amended with mineral nutrients and incubated in an airtight container with continuous forced aeration. Total CO(inf2) and (sup14)CO(inf2) in the off-gas were trapped and quantified. Soil samples were Soxhlet extracted with dichloromethane at seven time points during the 150-day incubation period, and the extracted soil was subjected to further fractionation in order to recover reversibly and irreversibly bound radiocarbon. Radiocarbon recovery was 100% (plusmn) 3% for each time point. During the first 50 days of incubation, no (sup14)CO(inf2) was evolved, but over the next 100 days, 50% of the BaP radiocarbon was evolved as (sup14)CO(inf2). At 150 days, only 5% of the intact BaP and 23% of the crude oil remained. Of the remaining radiolabel, 20% was found in solvent-extractable metabolites and 25% was incorporated into soil organic matter. Only 1/10 of this could be solubilized by chemical hydrolysis. An abiotic control experiment exhibited binding of only 2% of the BaP, indicating the microbial nature of the BaP transformations. We report that in soil containing suitable cosubstrates, BaP can be completely degraded.

Journal Article↗

High incidence of loss of heterozygosity and abnormal imprinting of H19 and IGF2 genes in invasive cervical carcinomas. Uncoupling of H19 and IGF2 expression and biallelic hypomethylation of H19.

The few imprinted genes characterized so far include the insulin-like growth factor-2 gene (IGF2) coding for a foetal growth factor and the H19 gene whose normal function is unknown but which is likely to act as an RNA with an antitumour effect. IGF2 is expressed by the paternal allele and H19 by the maternal allele. This reciprocal expression is quite interesting because both H19 and IGF2 genes are located close to each other on chromosome 11p15.5 in a region subject to loss of heterozygosity (LOH). Moreover, loss of imprinting (LOI) or biallelic expression has been proposed as an epigenetic mechanism for tumorigenesis in a variety of human cancers including Wilms' tumour. In this study we report the LOH, LOI and methylation status of H19 and IGF2 genes in 29 invasive cervical carcinomas of different clinical stages. Fourteen (48%) and 13 (45%) tumours were heterozygous for H19 and IGF2 respectively. LOH for H19 and IGF2 genes were found in 2 of 14 (14%) and 3 of 13 (23%) informative tumours, respectively. LOI of H19 and IGF2 was detected in 2 of 12 (17%) and 5 of 10 (50%) tumours with no LOH, respectively. More interestingly, monoallelic expression of the otherwise silent H19 allele (allele switch) was observed in 2 of 12 (17%) tumours and biallelic expression of IGF2 was detected in one specimen of normal cervix adjacent to the tumour. The expressing H19 allele, and to a lower degree also the silent allele, were hypomethylated in tumours suggesting that demethylation of both H19 alleles may be associated with an early step of imprinting alteration. In cervical cancer H19 and IGF2 expressions could be independently regulated. In conclusion, our data suggest that H19 and IGF2 genes, via deletions and/or abnormal imprinting, could play a crucial role in a large proportion (58%) of cervical cancers where they may be associated with disease progression.

Alleles↗

[High incidence of p53 mutations in primary and metastatic head and neck tumors. Frequent protein overexpression in normal epithelium].

Mutation of the p53 tumor suppressor gene is the most commonly observed gene alteration in human cancers. In order to identify new prognostic factors and tumor aggressiveness in squamous cell head and neck carcinomas, we analyzed 50 node metastases and 28 primary tumors including 13 matched specimens for p53 alterations. Mutations were found in 54 (69%) tumors, 76% of which were missense, 9% were nonsense and 15% were microdeletions or microinsertions. Twenty-five mutations were transitions mostly G-->A (40%) and 20 were transversions mostly G-->T (25%) thus confirming the role of tobacco carcinogens in the induction of these mutations. For eight patients mutations were observed in matched primary tumors and metastases, indicating clonal dissemination of tumor cells in most of these carcinomas. Furthermore the incidence of mutations was not different in primary tumors and node metastases indicating that this gene alteration was not related to the metastatic dissemination. No correlation was found between mutation and clinical parameters, the 8-year survival rates were not different (log rank test: P = 0.49) in patients with and without mutation. There was a good correlation between p53 mutation and protein overexpression (Fisher's exact test: P < 10(-4). Interestingly, immunostaining was also observed in basal cells from normal mucosa and in early lesions adjacent to the primary tumor in 11/15 specimens irrespective of the presence of mutation in the corresponding tumors. p53 protein overexpression may therefore constitute a biomarker for early stages of carcinogenesis of the head and neck epithelium.

Carcinoma, Squamous Cell↗

High incidence of p53 alterations (mutation, deletion, overexpression) in head and neck primary tumors and metastases; absence of correlation with clinical outcome. Frequent protein overexpression in normal epithelium and in early non-invasive lesions.

We have analysed 78 head and neck carcinomas (50 node metastases and 28 primary tumors including 13 matched specimens) in 65 patients for p53 alterations. Mutations were found in 54 (69%) tumors. Of the 53 mutations within exons, 40 (76%) were missense, five (9%) nonsense and eight (15%) microdeletions or microinsertions. Twenty-five (47%) mutations were transitions mostly G-->A (40%) and 20 (38%) were transversions, mostly G-->T (25%), thus confirming the role of tobacco carcinogens in the induction of these mutations. The incidence of mutations was not different in primary tumors (68%) and node metastases (70%) indicating that this gene alteration was not related to the metastatic dissemination. For eight patients, mutations were observed in matched primary tumors and metastases, indicating clonal dissemination of tumor cells in most of these carcinomas. There was a good correlation between mutations and protein overexpression (Fisher's exact test P < 10(-4). Immunostaining was also observed in basal cells from normal epithelium and in early lesions adjacent to the primary tumor in 11/15 (73%) specimens irrespective of the presence of mutation in the corresponding tumors. These data confirm that p53 overexpression is an early event in the multistep process of epithelial cell carcinogenesis. Loss of heterozygosity for the TP53 locus was detected in 54% of tumors but no association was found with mutation (Fisher's exact test P = 0.14). No mdm-2 amplification was detected in any tumors. No correlation was found between mutation and clinical parameters, the 5-year survival rates were not different (log rank test P = 0.39) in patients with and without mutation. In conclusion, we have shown that p53 gene mutations and deletions and protein overexpression are frequent in the most aggressive head and neck carcinomas but are not associated with disease progression. The presence of protein in normal mucosa and in non-invasive lesions may constitute a biomarker for early stages of carcinogenesis.

Base Sequence↗

Familial clustering of breast cancer: possible interaction between DNA repair proficiency and radiation exposure in the development of breast cancer.

The capacity of peripheral blood lymphocytes to repair X-ray-induced DNA damage, manifest as chromatid damage 30-90 min after G2-phase X-irradiation, was measured among available members of a family exhibiting a cluster of breast-cancer cases occurring in one generation. The cancer patients had been exposed to repeated chest fluoroscopic examinations during early childhood and adolescence. The development of breast cancer was correlated with DNA repair proficiency and history of radiation exposure. The results of the family study provide preliminary support for the hypothesis that a deficiency in repair of X-irradiation DNA damage may be a susceptibility factor for the development of breast cancer. This hypothesis, however, requires confirmation in a larger study. Studying the combined effect of susceptibility factors and environmental exposures may enhance our knowledge of the etiology of breast cancer and provide leads for effective prevention strategies aimed at reducing exposures or altering susceptibility to unavoidable exposures.

Breast Neoplasms↗

Mutagenesis of yeast MW104-1B strain has identified the uncharacterized PMS6 DNA mismatch repair gene locus and additional alleles of existing PMS1, PMS2 and MSH2 genes.

The haploid yeast Saccharomyces cerevisiae MW104-1B strain was disomic for chromosome III (n + 1) and carried DNA mismatches at three different heteroallelic loci; leu2 (leu2-1/leu2-27), thr4 (thr4-1/thr4-16) and his4 (his4-4/his4-519) (Williamson, 1984). We mutagenized the MW104-1B strain and identified seven mutant isolates that display elevated mitotic/meiotic prototrophs due to mismatch repair failures at heteroallelic loci. Three mutants (pms1, pms2 and pms3) isolated earlier from MW104-1B were shown to correct in vitro constructed plasmids with defined DNA mismatches (G/T, A/C, G/G, etc.) poorly (Kramer et al., 1989a). Complementation tests were performed by crossing all seven new mutant isolates to pms1 and pms2 mutants and assaying for mutant phenotype in the diploids. Four mutant isolates failed to complement the two known pms alleles (pms1-1 and pms2-1). Two other mutant isolates complemented the pms1-1 and pms2-1 alleles, but failed to complement each other and were named as the pms5-1 allele of an uncharacterized gene (PMS5). One other mutant isolate complemented the pms1-1, pms2-1 and pms5-1 alleles and was named as the pms6-1 allele of another uncharacterized gene (PMS6). Subsequently, the pms5-1 mutant allele was shown to be complemented by a plasmid borne yeast MSH2 gene, implying that it is an allele of MSH2 (PMS5). The human homologs (hMSH2 and hMLH1) of two yeast DNA mismatch repair genes (MSH2 and MLH1) have been cloned recently and shown to be responsible for hereditary nonpolypnosis colon cancer (HNPCC) (Fishel et al., 1993; Leach et al., 1993; Bronner et al., 1994; Papadopoulos et al., 1994).

Alleles↗

Recombinant repair of diverged DNAs: a study of homoeologous chromosomes and mammalian YACs in yeast.

Recombinational repair is the means by which DNA double-strand breaks (DSBs) are repaired in yeast. DNA divergence between chromosomes was shown previously to inhibit repair in diploid G1 cells, resulting in chromosome loss at low nonlethal doses of ionizing radiation. Furthermore, 15-20% divergence prevents meiotic recombination between individual pairs of Saccharomyces cerevisiae and S. carlsbergensis chromosomes in an otherwise S. cerevisiae background. Based on analysis of the efficiency of DSB-induced chromosome loss and direct genetic detection of intragenic recombination, we conclude that limited DSB recombinational repair can occur between homoeologous chromosomes. There is no difference in loss between a repair-proficient Pms+ strain and a mismatch repair mutant, pms1. Since DSB recombinational repair is tolerant of diverged DNAs, this type of repair could lead to novel genes and altered chromosomes. The sensitivity to DSB-induced loss of 11 individual yeast artificial chromosomes (YACs) containing mouse or human (chromosome 21 or HeLa) DNA was determined. Recombinational repair between a pair of homologous HeLa YACs appears as efficient as that between homologous yeast chromosomes in that there is no loss at low radiation doses. Single YACs exhibited considerable variation in response, although the response for individual YACs was highly reproducible. Based on the results with the yeast homoeologous chromosomes, we propose that the potential exists for intra- YAC recombinational repair between diverged repeat DNA and that the extent of repair is dependent upon the amount of repeat DNA and the degree of divergence. The sensitivity of YACs containing mammalian DNA to ionizing radiation-induced loss may thus be an indicator of the extent of repeat DNA.

Aneuploidy↗

Mitotic hyperploidy for chromosomes VIII and III in Saccharomyces cerevisiae.

The arg4-8 and cup1s markers comprise a copy-number-dependent signal device in the yeast Saccharomyces cerevisiae. These alleles permit reliable discrimination between euploid and disomic haploids as well as between euploid and trisomic diploids. To investigate and compare inherent inter-chromosomal differences as regards propensity for hyperploidy, we transplaced arg4-8 and cup1s by deleting them from chromosome VIII and then re-introducing them at the leu2 locus on chromosome III. The rate of chromosome gain was significantly greater for the chromosome III construct compared to the native chromosome VIII, in both diploid and haploid strains. In addition, more coincident aneuploidy for other chromosomes was found among chromosome VIII hyperploids compared to chromosome III hyperploids.

Aneuploidy↗

Multicopy CUP1 plasmids enhance cadmium and copper resistance levels in yeast.

A 3.3 kb fragment of yeast genomic DNA was isolated by screening a genomic library constructed in the high copy number 2 micron plasmid YEp351 vector for clones capable of enhancing the degree of resistance of Saccharomyces cerevisiae strain MW3070-8B to cadmium. The insert contained two complete copies of the CUP1 gene open reading frame (183 bp), including the upstream promoter sequences (450 bp) with two conserved metal responsive cis-acting elements. Northern analysis showed that addition of cadmium (0.02 microM) or copper (50 microM) to overnight liquid cultures of yeast induced expression of CUP1 transcripts from both chromosomal and plasmid-borne gene copies. The cloned 3.3 kb DNA in a high copy number plasmid restored copper resistance to the sensitive strain LS70-3B delta, deleted for the CUP1 gene (cup 1 delta), but failed to restore cadmium resistance. Thus, CUP1 gene expression in yeast appears to be influenced differently by cadmium and copper ions. Resistance to heavy metal poisoning resulted from enhanced gene product levels attributable to amplification of the CUP1 gene as well as to increased transcriptions. Two distinct gene product levels mediate cadmium and copper resistance; a higher gene product level was required to confer cadmium resistance.

Amino Acid Sequence↗

Gene conversions within the Cup1r region from heterologous crosses in Saccharomyces cerevisiae.

Meiotic recombination among unselected tetrads was analyzed genetically and physically in a heterologous cross where one parent carried six copies of a 1.6 kb CUP1 repeat while the other parent carried seven copies of a 1.1 kb repeat. In the heterologous cross, 140 unselected, complete tetrads were subjected to Southern analysis and 20% exhibited meiotic copy number alterations at the CUP1 locus. Most events, more than 75%, involved only a single spore of a tetrad, and were largely intrachromosomal or sister chromatid events. However, some conversions and associated crossovers between homologs were also observed. We propose that the high level of heterologies interferes with homologous exchanges and leads to an increase in intrachromosomal events.

Blotting, Southern↗

Microconversion between murine H-2 genes integrated into yeast.

Patchwork homology observed between divergent members of polymorphic multigene families is thought to reflect evolution by short-tract gene conversion (nonreciprocal recombination), although this mechanism cannot usually be confirmed in higher organisms. In contrast to meiotic conversions observed in laboratory yeast strains, apparent conversions between polymorphic sequences, such as the class I loci of the major histocompatibility complex (MHC), are short and do not seem to be associated with reciprocal recombination (crossover, exchanges). We have now integrated two nonallelic murine class I genes into yeast to characterize their meiotic recombination. We found no crossovers between the MHC genes, but short-tract 'microconversions' of 1-215 base-pairs were observed in about 6% of all meioses. Strikingly, one of these events was accompanied by a single base-pair mutation. These results underscore both the importance of meiotic gene conversion and sequence heterology in determining conversion patterns between divergent genes.

Animals↗

Unequal crossing-over and gene conversion at the amplified CUP1 locus of yeast.

Meiotic recombination was analyzed between two twelve-copy arrays of a gene amplification at the CUP1 locus of Saccharomyces cerevisiae. Utilizing Southern analysis to identify spores with non-parental repeat arrays, we find that approximately 11% of a sample with 202 unselected tetrads possess at least one nonparental spore array. Both reciprocal and non-reciprocal changes are observed. The data suggest a model in which frequent mispairing among identical copies of the 2.0 kb repeat unit leads to the formation of unpaired loops containing integral numbers of repeat units. In this model, conversions involving the loops lead to non-reciprocal changes in arrays: about half are associated with reciprocal exchange, and net increases in repeat unit numbers occur about as frequently as net decreases. Thus, the known properties of gene conversion can account for all the segregations we observe.

Blotting, Southern↗