Fine structure effect in electron impact ionization.
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Journal Article↗
Biomedical subjects
Y Shen
Publications and source records attributed to Y Shen.
Turbulent convection over rough surfaces.
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Journal Article↗
Age-specific prostate-specific antigen: a reassessment.
BACKGROUND: Our objective was to compare expected survival benefits when screening for prostate cancer with PSA, using an age-specific bound relative to a cutoff of 4.0 ng/ml. METHODS: We used a decision analysis modeling the cancer yield in a cohort screened by both screening tests, and the survival of cancer cases given screen detection and in the absence of screening. Expected cancer yields and positive predictive values were from an ultrasound-guided biopsy series. Stage distributions of screen-detected cases were obtained from the literature. For localized causes, survival given screen detection was assumed to be equal to normal life expectancy for the population. For these cases, survival in the absence of screening was modeled as time from clinical diagnosis to death added to time remaining after time of screen and before clinical diagnosis was made (lead time). For nonlocalized cases at screen detection, survival given screen detection was assumed to be equal to survival in the absence of screening. The average difference between expected survival with and without screening as calculated for age-specific PSA and for PSA > 4.0 ng/ml and compared. RESULTS: Average years of life saved per subject screened using PSA > 4.0 ng/ml were comparable to those using the age-specific bound. Average years of life saved per cancer case, however, appeared to be potentially greater for PSA > 4.0 ng/ml than for age-specific. PSA. PSA > 4.0 ng/ml detected markedly more prostate cancer cases than age-specific PSA. CONCLUSIONS: Using a bound of 4.0 ng/ml for all ages appears to be more efficient in identifying men with cancer in a screening cohort, which translates into a greater expected survival benefit per cancer case.
Aged↗
Comparative study of skeletal response to estrogen depletion at red and yellow marrow sites in rats.
BACKGROUND: Skeletal sites with red and yellow marrow may respond differently to estrogen depletion. To investigate this possibility, bone histomorphometric changes were compared at skeletal sites with different marrow composition in ovariectomized (OVX) rats, an animal model for postmenopausal bone loss. METHODS: Female rats were OVX or sham-operated at 3 months of age and sacrificed at 1 month or 1 year postsurgery. Eight rats were sacrificed at the beginning of the study as baseline controls. The proximal tibial metaphysis (PTM) and first lumbar vertebra (LV), bone sites with red marrow, as well as the distal tibial metaphysis (DTM) and fifth caudal vertebra (CV), bone sites with yellow marrow, were processed undecalcified for quantitative bone histomorphometry. RESULTS: In control rats, an age-related decrease in bone turnover was observed at all bone sites. Indices of bone turnover, such as osteoclast surface, mineral apposition rate, and bone formation rate, were lower in the DTM and CV compared to the PTM and LV. At 1 month postovariectomy, most bone resorption and formation indices at all bone sites were increased in OVX rats relative to control rats, but decreased cancellous bone volume was found only in the PTM. At 1 year postovariectomy, OVX rats exhibited severe cancellous osteopenia in the PTM and moderate cancellous osteopenia in the LV. In contrast, cancellous osteopenia did not develop in the DTM and CV even at 1 year postovariectomy, despite the fact that OVX rats still exhibited a trend for increased bone turnover at these yellow marrow sites. CONCLUSIONS: The results indicate that unlike skeletal sites with red marrow, estrogen depletion does not induce cancellous osteopenia at skeletal sites with yellow marrow in rats. Since increased bone turnover occurred at the various skeletal sites in OVX rats regardless of marrow composition, this skeletal alteration does not by itself induce cancellous bone loss. An imbalance between bone resorption and formation appears to be the major factor that determines the magnitude of bone loss at a given skeletal site in OVX rats. Differences in the anatomical characteristics of red and yellow marrow that may form a basis for these findings are discussed.
Age Factors↗
Lipoxygenase metabolites induced expression of adhesion molecules and transendothelial migration of monocyte-like HL-60 cells is linked to protein kinase C activation.
Studies have shown that, among lipoxygenase metabolites examined, 15(S)-hydroperoxy-5,8,11,13-eicosa-tetraenoic acid (15[S]-HPETE), at micromolar concentrations, selectively causes injury to cultured endothelial cells. We investigated whether physiologically relevant concentrations of lipoxygenase metabolites affected the expression of cell adhesion molecules (CAMs) involved in the adhesion of leukocytes and/or the accumulation of leukocytes in the vascular endothelium, these being the initial events in endothelial cell injury. Among lipoxygenase metabolites, 15(S)-HPETE and 12(S)-HETE, at nanomolar concentrations, induced surface expression of a subset of cell adhesion molecules (CAM), ICAM-1, ELAM-1, and VCAM-1, in human umbilical vein endothelial cells (HUVEC), which is associated with an increased binding activity of the transcription factor, NF-kappa B, to the consensus motif common to the CAM genes in the HUVEC nuclear extracts. Furthermore, 15(S)-HPETE (1 nM) caused a threefold increase in the rate of transendothelial migration of vitamin D3-differentiated HL-60 monocyte-like cells and showed a thirtyfold increase in the phosphorylation of PECAM-1, an adhesion molecule involved in endothelial cell-cell adhesion. Both an antibody to PECAM-1 and the protein kinase C inhibitor, GF 109203X, reduced 15(S)-HPETE-induced transmigration of monocyte-like HL-60 cells by approximately 75% and 85%, respectively. Treatment of HUVEC with a phosphatase inhibitor, calyculin A, augmented both the phosphorylation of PECAM-1 and transmigration of monocyte-like HL-60 cells induced by 15(S)-HPETE. Our results show that 15(S)-HPETE, at physiological concentrations, induced activation of protein kinase C in HUVEC and leads to the phosphorylation of PECAM-1, thus facilitating the migration of monocyte-like HL-60 cells across the endothelial cell monolayer. It is suggested that phosphorylation/dephosphorylation events in PECAM-1 are important in regulating the trafficking of monocytes across the endothelial cell monolayer.
Animals↗
Adhesion molecule expression and complement activation in vessel walls in synovial tissue from patients with chronic inflammatory joint disease.
Histopathology demonstrating a manifest vasculitis is a rare event in synovial tissue (ST) from patients with chronic inflammatory joint disease. As a possibly more subtle sign of a vasculitic process, complement activation in vessels in ST was studied. In the same tissues, the expression of the adhesion molecules ICAM-1 and E-selectin in vessel walls was examined, to see if the expression was related to vasculitic processes. The study was performed by use of direct immunofluorescence technique on cryostat sections of ST, using mouse monoclonal antibodies to the terminal complement complex (TCC, C5b-9), ICAM-1 and E-selectin. Expression of ICAM-1 was found in the vessel walls in all of 28 tissues tested, whereas E-selectin was found in 4 cases and TCC in 11. E-selectin and TCC were found together in only 1 tissue. The study supports the view that ICAM-1 is always, or nearly always, present in vessel walls in synovial tissue from patients with chronic inflammatory joint disease. E-selectin and TCC may also be present, but the lack of association between these two proteins suggests that the mechanism leading to a complement mediated vasculitic process is different from that causing expression of E-selectin.
Animals↗
Construction and characterization of three region-specific microdissection libraries for human chromosome 18.
Three region-specific libraries for the entire human chromosome 18 were constructed using microdissection and Mbol linker-adaptor microcloning techniques. The libraries included 18pter-p11.1 (designated 18P library), 18q11.1-q12.3 (18Q1 library), and 18q21.1-qter (18Q2 library). Samples of the microclones from each library were analyzed in detail. The insert sizes ranged between 50-600 bp, with a mean of 180-220 bp for the three libraries. The libraries contained approximately 40-60% microclones with unique sequence inserts. More than 30 unique sequence microclones from each library were analyzed by Southern blot hybridization to demonstrate that they are human specific and were derived from chromosome 18. The human genomic HindIII fragments hybridized to each microclone were determined and microclones cross-hybridized to rodent species were identified. These region-specific libraries and the unique sequence microclones from the libraries are useful reagents for (1) isolating highly polymorphic microsatellite markers for refined linkage analysis, (2) identifying corresponding YAC, BAC or other clones with large inserts for contig assembly and high resolution physical mapping, (3) isolating cDNA clones from the dissected region, and (4) convenient sequencing of the microclones to prepare high density markers and sequence-tagged sites (STSs). Such applications have been demonstrated in a series of similarly constructed microdissection libraries from other regions of the human genome.
Chromosome Mapping↗
Skeletal effects of calcitonin treatment and withdrawal in ovariectomized rats.
The study was designed to determine, by histomorphometric techniques, bone changes as a function of time during long-term treatment with salmon calcitonin (CT) and after withdrawal of the hormone in ovariectomized (OVX) rats. Groups of OVX rats were treated with vehicle alone or CT on alternate days for 30, 60, or 90 days. Additional groups of sham-operated control rats were treated with vehicle alone. Rats from each of the three groups were sacrificed at each time point. All treatments in the remaining rats were then terminated at 90 days, followed by sacrifice of rats from each group at 30 and 60 days after withdrawal of vehicle or CT treatment. The proximal tibia from each animal was processed undecalcified for quantitative bone histomorphometry. Compared with control rats, the proximal tibiae of vehicle-treated OVX rats were characterized by cancellous osteopenia and significant increases in osteoclast surface, osteoblast surface, mineralizing surface, mineral apposition rate, and bone formation rate. CT treatment of OVX rats partially prevented cancellous bone loss by approximately 50% and significantly decreased most of the above indices of bone turnover relative to vehicle-treated OVX rats. However, soon after withdrawal of CT, OVX rats previously treated with the hormone exhibited rapid loss of cancellous bone associated with increased bone turnover. These results in an animal model of estrogen depletion suggest that early postmenopausal women who are withdrawn from prophylactic CT treatment may be at high risk for subsequent bone loss.
Animals↗
Molecular dissection of a cosmid from a gene-rich region in 17q21 and characterization of a candidate gene for alpha-N-acetylglucosaminidase with two cDNA isoforms.
A cosmid mapped to human Chromosome (Chr) 17q21, c140c10, was found to contain a CpG island. We completed the sequence analysis of c140c10 because of two considerations: the cosmid contained an STS from the 17-beta-hydroxysteroid dehydrogenase gene (17-HSD), which was believed to be a neighbor of the breast cancer susceptibility gene, BRCA1; CpG islands are usually associated downstream and/or upstream of human genes. Computer-based exon trapping of the cosmid sequence revealed putative additional exons. With two of those exons used as a probe to screen human placental cDNA libraries, two cDNA isoforms for a novel gene, designated as ufHSD, were isolated. The amino acid sequence of the open reading frames of the cDNA showed no significant homology to any protein in the data base. However, it is possible that our cDNAs are from the gene for alpha-acetylglucosaminidase, which has recently been localized to the same region. Northern analyses show that the major isoform is expressed in all tissues tested, with the highest expression in blood leukocytes and lowest in brain. Finally, our study has shown that the 46.7-kb cosmid c140c10 encompasses loci for five genes and pseudo-genes: PsiPTP4A, ufHSD, 17-HSDI, 17-HSDII, and 22A1.
Acetylglucosaminidase↗
Detection of elevated reactive oxygen species level in cultured rat hepatocytes treated with aflatoxin B1.
Accumulating evidence demonstrates that oxidative damage is one of the underlying mechanisms to the cytotoxicity and carcinogenicity of AFB1. The main objective of this study is to show that AFB1 increases reactive oxygen species (ROS) formation in hepatocytes. The ROS level was detected using a fluorescence probe, 2',7'-dichlorofluorescin diacetate (DCFH-DA), which could be converted to highly fluorescent dichlorofluorescein (DCF) with the presence of intracellular ROS. It was found that AFB1 exposure significantly enhanced DCF fluorescence formation in cultured rat hepatocytes. A dose-response of AFB1 was also observed within the range of 10 nM to 1000 nM. Catalase (CAT) was able to completely prevent the increase of DCF fluorescence in AFB1-treated cells in a dose-dependent manner (from 500 to 2000 U/ml). Moreover, the significant inhibitory effects of desferrioxamine (DFO) and dimethyl sulfoxide (DMSO) on DCF fluorescence formation were also observed in both control and AFB1-treated hepatocytes. Therefore, results from the present study provide in vitro evidence indicating the generation of ROS in cultured rat hepatocytes caused by AFB1 exposure. It is postulated that the metabolic process of AFB1 by cytochrome P450 might be the possible source of the elevated ROS level in AFB1-treated hepatocytes. The enhanced level of ROS may be responsible for the oxidative damage caused by AFB1, which may ultimately contribute to the cytotoxic and carcinogenic effects of AFB1.
Aflatoxin B1↗
A comparison of the skeletal effects of intermittent and continuous administration of calcitonin in ovariectomized rats.
The study was designed to compare the skeletal effects of intermittent and continuous administration of calcitonin (CT) in ovariectomized (OVX) rats. Female rats were sham operated or OVX at 3 months of age and treated for 6 weeks with vehicle or salmon CT. Sham-operated control rats were injected subcutaneously with vehicle on alternate days. One group of OVX rats was treated with vehicle intermittently by subcutaneous injection or continuously via Alzet osmotic minipumps. The remaining OVX rats were treated with CT by either subcutaneous injections (16 U/kg) on alternate days or by continuous infusion via minipumps at a daily dose of 8 U/kg. OVX rats treated with CT continuously were mildly hypocalcemic compared with all other groups. The proximal tibial metaphyses of vehicle-treated OVX rats were osteopenic with a cancellous bone volume at only 28% of the vehicle-treated control level. This bone loss was associated with increased indices of bone turnover such as osteoclast surface, osteoblast surface, and bone formation rate. Cancellous bone volume in OVX rats treated with CT either intermittently or continuously was significantly higher than that of vehicle-treated OVX rats, but lower than that of vehicle-treated control rats. Treatment of OVX rats with intermittent or continuous CT significantly decreased all indices of bone turnover compared with vehicle-treated OVX rats. However, osteoclast and osteoblast surfaces of OVX rats treated with CT continuously were still significantly higher than those of vehicle-treated control rats. These results indicate that intermittent and continuous administration of CT had similar skeletal effects in OVX rats. Both treatment regimens depressed bone turnover and partially prevented cancellous bone loss in the estrogen-deplete skeleton.
Analysis of Variance↗
Skeletal response to corticosteroid deficiency and excess in growing male rats.
The study was designed to investigate bone histomorphometric changes induced by corticosteroid deficiency and supplementation at different dose levels in the rat skeleton. Male rats were adrenalectomized (ADX) or sham-operated and divided into six groups. At 2 days after surgery, sham-operated control rats (CON + PLA) and one group of ADX rats (ADX + PLA) were implanted subcutaneously (s.c.) with placebo pellets. ADX rats in the remaining four groups (ADX + C25, ADX + C50, ADX + C100, and ADX + C300) were implanted sc with corticosterone pellets designed to release 25, 50, 100, or 300 mg of the hormone over a 60 day period. Each ADX rat was also implanted sc with an aldosterone pellet (2.5 mg) similarly designed to release its contents over the same time period. All rats were killed at 3 weeks after implantation of pellets. Terminal blood samples were collected for serum biochemistry and the proximal tibial metaphyses (PTM), tibial diaphyses, and first lumbar vertebrae (LV) were processed undecalcified for quantitative bone histomorphometry. A dose-dependent increase in serum corticosterone concentration was observed in ADX rats implanted with hormone pellets. In comparison to CON + PLA rats, ADX + PLA rats had lower cancellous bone volume associated with a stimulation in longitudinal bone growth, an increase in mineral apposition rate, and a trend for increased osteoclast and osteoblast surfaces in PTM. In contrast, cancellous bone of ADX + C25 rats was preserved at nearly the CON + PLA level. However, the higher doses of corticosterone increased cancellous bone mass, but decreased longitudinal bone growth and all indices of bone resorption and formation in a dose-dependent manner in PTM. Similar cancellous bone changes were observed in the LV of corticosterone-treated rats, with the exception of a lack of an hormonal effect on cancellous bone mass. In the tibial diaphysis, corticosterone inhibited periosteal bone formation in a dose-dependent manner, but did not affect cortical bone mass. The results indicate that corticosteroid deficiency induces cancellous osteopenia, whereas supplementation with a near physiologic dose of the hormone prevents this bone loss in ADX rats. Furthermore, corticosteroid excess inhibits bone growth and bone turnover in a dose-dependent manner, but does not induce cancellous osteopenia in growing male rats.
Adrenal Cortex Hormones↗
Third-time coronary artery bypass operations: surgical strategy and results.
BACKGROUND: Increasingly, patients are returning for a second, third, and even fourth coronary artery bypass graft (CABG) procedure. METHODS: This report reviews the in-hospital and long-term outcomes for 102 patients undergoing a third or fourth CABG at Emory University from December 1977 to April 1994. RESULTS: The mean interval from the first to second CABG was 5.2 +/- 3.5 years and from the second to the third CABG 6.8 +/- 4.1 years. The mean age was 6 +/- 9 years, 91% were male, 33% had hypertension, 16% diabetes, 86% class III or IV angina (Canadian Cardiovascular Society), 4.4% congestive failure (New York Heart Association), and 73% three-vessel disease. The in hospital mortality rate was 9.8%, with a perioperative myocardial infarction rate of 8.8% and a stroke rate of 1.9%. CONCLUSIONS: These perioperative mortality and myocardial infarction rates are several times higher than those reported for initial revascularizations or first-time redo CABG operations. However, the 5- and 10-year survival rates of 79% and 59%, respectively, and a myocardial infarction-free survival of 62% at 5 years, the benefits of a third-time CABG procedure are apparent for this high-risk group of patients.
Aged↗
Identification of FMR2, a novel gene associated with the FRAXE CCG repeat and CpG island.
Five folate-sensitive fragile sites have been identified at the molecular level to date. Each is characterized by an expanded and methylated trinucleotide repeat CGG (CCG). Of the three X chromosome sites, FRAXA, FRAXE and FRAXF, the former two are associated with mental retardation in their expanded forms. FRAXA expansion results in fragile X syndrome due to down regulation of expression of the FMR1 gene, which carries the hypermutable CGG repeat in the 5' untranslated portion of its first exon. Mild mental retardation without consistent physical findings has been found associated with expanded CCG repeats at FRAXE. We have identified a large gene (FMR2) transcribed distally from the CpG island at FRAXE, and down-regulated by repeat expansion and methylation. The gene is novel, expressed in adult brain and placenta, and shows similarity with another human protein, MLLT2, expressed from a gene at chromosome 4q21 involved in translocations found in acute lymphoblastic leukaemia (ALL) cells. Identification of this gene will facilitate further studies to determine the role of its product in FRAXE associated mental deficiency.
Adult↗
Duplication of a gene-rich cluster between 16p11.1 and Xq28: a novel pericentromeric-directed mechanism for paralogous genome evolution.
We have identified a 26.5 kb gene-rich duplication shared by human Xq28 and 16p11.1. Complete comparative sequence analysis of cosmids from both loci has revealed identical Xq28 and 16p11.1 genomic structures for both the human creatine transporter gene (SLC6A8) and five exons of the CDM gene (DXS1357E). Overall nucleotide similarity within the duplication was found to be 94.6%, suggesting that this interchromosomal duplication occurred within recent evolutionary time (7-10 mya). Based on comparisons between genomic and cDNA sequence, both the Xq28 creatine transporter and DXS1357E genes are transcriptionally active. Predicted translation of exons and RT-PCR analysis reveal that chromosome 16 paralogs likely represent pseudogenes. Comparative fluorescent in situ hybridization (FISH) analyses of chromosomes from various primates indicate that this gene-rich segment has undergone several duplications. In gorilla and chimpanzee, multiple pericentromeric localizations on a variety of chromosomes were found using probes from the duplicated region. In other species, such as the orangutan and gibbon, FISH signals were only identified at the distal end of the X chromosome, suggesting that the Xq28 locus represents the ancestral copy. Sequencing of the 16p 11.1/Xq28 duplication breakpoints has revealed the presence of repetitive immunoglobulin-like CAGGG pentamer sequences at or near the paralogy boundaries. The mobilization and dispersal of this gene-rich 27 kb element to the pericentromeric regions of primate chromosomes defines an unprecedented form of recent genome evolution and a novel mechanism for the generation of genetic diversity among closely related species.
Animals↗
Characterization of 16S rRNA genes from oil field microbial communities indicates the presence of a variety of sulfate-reducing, fermentative, and sulfide-oxidizing bacteria.
Oil field bacteria were characterized by cloning and sequencing of PCR-amplified 16S rRNA genes. A variety of gram-negative, sulfate-reducing bacteria was detected (16 members of the family Desulfovibrionaceae and 8 members of the family Desulfobacteriaceae). In contrast, a much more limited number of anaerobic, fermentative, or acetogenic bacteria was found (one Clostridium sp., one Eubacterium sp., and one Synergistes sp.). Potential sulfide oxidizers and/or microaerophiles (Thiomicrospira, Arcobacter, Campylobacter, and Oceanospirillum spp.) were also detected. The first two were prominently amplified from uncultured production water DNA and represented 28 and 47% of all clones, respectively. Growth on media containing sulfide as the electron donor and nitrate as the electron acceptor and designed for the isolation of Thiomicrospira spp. gave only significant enrichment of the Campylobacter sp., which was shown to be present in different western Canadian oil fields. This newly discovered sulfide oxidizer may provide a vital link in the oil field sulfur cycle by reoxidizing sulfide formed by microbial sulfate or sulfur reduction.
Bacteria↗
DNA binding domain and subunit interactions of transcription factor IIIC revealed by dissection with poliovirus 3C protease.
Transcription factor IIIC (TFIIIC) is a general RNA polymerase III transcription factor that binds the B-box internal promotor element of tRNA genes and the complex of TFIIIA with a 5S rRNA gene. TFIIIC then directs the binding of TFIIIB to DNA upstream of the transcription start site. TFIIIB in turn directs RNA polymerase III binding and initiation. Human TFIIIC contains five different subunits. The 243-kDa alpha subunit can be specifically cross-linked to B-box DNA, but its sequence does not reveal a known DNA binding domain. During poliovirus infection, TFIIIC is cleaved and inactivated by the poliovirus-encoded 3C protease (3Cpro). Here we analyzed the cleavage of TFIIIC subunits by 3Cpro in vitro and during poliovirus infection of HeLa cells. Analyses of the DNA binding activities of the resulting subcomplexes indicated that an N-terminal 83-kDa domain of the alpha subunit associates with the beta subunit to generate the TFIIIC DNA binding domain. Cleavage with 3Cpro also generated an approximately 125-kDa C-terminal fragment of the alpha subunit which remained associated with the gamma and epsilon subunits.
3C Viral Proteases↗
Thoracic aortic aneurysm and aortic dissection: new endoscopic mode for three-dimensional CT display of aorta.
Three-dimensional (3D) endoscopic-mode software was used at helical computed tomography (CT) to evaluate distal aortic arch aneurysms (n = 12) and aortic dissections (n = 10); images were compared with two-dimensional (2D) axial source images. In distal aortic arch aneurysms, the 3D endoscopic mode depicted the relationship of the arterial orifices and the aneurysm, which is difficult to evaluate with 2D axial images alone. In aortic dissections, however, the 3D endoscopic mode did not provide additional information to that provided on the 2D axial source images.
Aged↗