PubMed Health⌕ Search

Biomedical subjects

D Sargent

Publications and source records attributed to D Sargent.

17 recordsLinked to original sources
PubMed2001

Guidelines 2000 for colon and rectal cancer surgery.

BACKGROUND: Oncologic resection techniques affect outcome for colon cancer and rectal cancer, but standardized guidelines have not been adopted. The National Cancer Institute sponsored a panel of experts to systematically review current literature and to draft guidelines that provide uniform definitions, principles, and practices. METHODS: Methods were similar to those described by the American Society of Clinical Oncology in developing practice guidelines. Experts representing oncology and surgery met to review current literature on oncologic resection techniques for level of evidence (I-V, where I is the best evidence and V is the least compelling) and grade of recommendation (A-D, where A is based on the best evidence and D is based on the weakest evidence). Initial guidelines were drafted, reviewed, and accepted by consensus. RESULTS: For the following seven factors, the level of evidence was II, III, or IV, and the findings were generally consistent (grade B): anatomic definition of colon versus rectum, tumor-node-metastasis staging, radial margins, adjuvant R0 stage, inadvertent rectal perforation, distal and proximal rectal margins, and en bloc resection of adherent tumors. For another seven factors, the level of evidence was II, III, or IV, but findings were inconsistent (grade C): laparoscopic colectomy; colon lymphadenectomy; level of proximal vessel ligation, mesorectal excision, and extended lateral pelvic lymph node dissection (all three for rectal cancer); no-touch technique; and bowel washout. For the other four factors, there was little or no systematic empirical evidence (grade D): abdominal exploration, oophorectomy, extent of colon resection, and total length of rectum resected. CONCLUSIONS: The panel reports surgical guidelines and definitions based on the best available evidence. The availability of more standardized information in the future should allow for more grade A recommendations.

Colonic Neoplasms↗
PubMed2000

The retro-GCN4 leucine zipper sequence forms a stable three-dimensional structure.

The question of whether a protein whose natural sequence is inverted adopts a stable fold is still under debate. We have determined the 2. 1-A crystal structure of the retro-GCN4 leucine zipper. In contrast to the two-stranded helical coiled-coil GCN4 leucine zipper, the retro-leucine zipper formed a very stable, parallel four-helix bundle, which now lends itself to further structural and functional studies.

Amino Acid Sequence↗
PubMed2000

Effects of Great Lakes fish consumption on brain PCB pattern, concentration, and progressive-ratio performance.

This study investigated the effects of consumption of Great Lakes fish on progressive ratio performance, and on the pattern and concentrations of brain polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethene (DDE), and mirex in the rat. Adult, male Sprague-Dawley rats were fed a 30% diet of either Lake Ontario salmon (LAKE), Pacific Ocean salmon, or lab chow control for 20 or 65 days. Following the treatment regimen, half the rats from each group were sacrificed immediately for gas chromatographic analysis of organochlorine contaminants, and the other half were tested on a multiple fixed-ratio-progressive-ratio reinforcement schedule and then sacrificed for analysis. Consumption of Lake Ontario fish resulted in significantly higher levels of brain PCBs, DDE, and mirex relative to controls, but still well within human exposure ranges (<1 microg/g fat). Consumption of Lake Ontario fish for 20 or 65 days produced an average brain PCB concentration of 457 and 934 ng/g fat, respectively. Consumption of laboratory rat chow or Pacific Ocean salmon for 20 or 65 days produced an average brain PCB concentration of 240, 464, and 441 ng/g fat, respectively. Moreover, both LAKE-fed groups showed a much more heavily chlorinated pattern of brain PCBs than all control groups, as evidenced by both significant increases in the most heavily chlorinated PCB congeners and significant increases in the average chlorine biphenyl. All LAKE brains contained significant concentrations of DDE and mirex, whereas no control brains contained any detectable quantities. Analysis of progressive-ratio performance indicated that LAKE rats responded normally during fixed-ratio schedules but quit significantly sooner than control rats on a progressive-ratio 5 (PR5) schedule, indicating reduced persistence on progressively leaner reinforcement schedules. Analysis of brain PCBs indicated that total PCBs were most strongly related to PR5 performance. These data indicate that consumption by rats of contaminated Lake Ontario fish produces (1) increased concentrations of PCBs, DDE, and mirex in the brain, (2) a more heavily chlorinated distribution of PCBs in the brain, and (3) reduced persistence of progressive-ratio reinforcement schedules. While these behavioral changes are related to brain PCB level, more work is necessary before the effects can be directly attributed to PCBs.

Adult↗
PubMed1995

Reducing health care delivery costs using clinical paths: a case study on improving hospital profitability.

The process of merging and benchmarking clinical and financial data is pivotal to the development of appropriate clinical pathways. Bristol Regional Medical Center (BRMC), facing the challenge of managed care organizations (MCOs), instituted this process and achieved significant cost savings, largely because of the working partnership between the administration and its medical staff. In DRG 89, Simple Pneumonia and Pleurisy, Age Greater than 17 with CC, data adjusted for severity of illness and cost of living were furnished to BRMC by HCIA Inc. Major benchmark or "best practice" variations were incorporated into new clinical pathways, leading to decreased resource use, no compromise in the quality of care, and a beneficial halo effect on other unrelated DRGs.

Decision Support Systems, Management↗
PubMed1990

Conformational stability of P22 tailspike proteins carrying temperature-sensitive folding mutations.

The thermostable tailspike endorhamnosidase of Salmonella phage P22 provides a model system for comparing the role of amino acid sequences in determining the intracellular folding pathway with their role in stabilizing the mature structural protein. Complete Raman band assignments are given here for the native form of the tailspike trimer in aqueous solution. Once correctly folded and assembled, the wild-type and two well-characterized mutant proteins, tsfIle258----Leu and tsfGly323----Asp, exhibit the same secondary structure in solution, consisting predominantly of beta-strand (56 +/- 5%) and turns (17 +/- 2%). Raman bands that are sensitive indicators of hydrogen-bonding interactions of tyrosine (phenolic OH) and tryptophan (indole NH) are unchanged between 30 and 80 degrees C in both wild type and tsf mutants. Similarly, Raman bands that are sensitive to changes in the hydrophobic environment of nonpolar side chains exhibit no significant temperature dependence in wild type and tsf mutants. In contrast, these conformational features are greatly altered by chemical denaturation of the tailspike with lithium halide and guanidine hydrochloride. In the chemically denatured tailspike, the beta-strand structure is substantially converted to irregular or "random coil" conformation. These findings confirm conclusions from physiological studies that the three-dimensional structures of the tsf mutants, once stabilized at permissive temperatures, are equivalent to the native structure of the wild type, and this structure is maintained at temperatures far above those that block the folding of the chain into the final native conformation.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1988

Secondary structure and thermostability of the phage P22 tailspike. XX. Analysis by Raman spectroscopy of the wild-type protein and a temperature-sensitive folding mutant.

The thermostable tailspike endorhamnosidase of bacteriophage P22 has been investigated by laser Raman spectroscopy to determine the protein's secondary structure and the basis of its thermostability. The conformation of the native tailspike, determined by Raman amide I and amide III band analyses, is 52 to 61% beta-sheet, 24 to 27% alpha-helix, 15 to 21% beta-turn and 0 to 10% other structure types. The secondary structure of the wild-type tailspike, as monitored by the conformation-sensitive Raman amide bands, was stable to 80 degrees C, denatured reversibly between 80 and 90 degrees C, and irreversibly above 90 degrees C. The purified native form of a temperature-sensitive folding mutant (tsU38) contains secondary structures virtually identical to those in the wild-type in aqueous solution at physiological conditions (0.05 M-Na+ (pH 7.5], at both permissive (20 degrees C) and restrictive (40 degrees C) temperatures. This supports previous results showing that the mutational defect at 40 degrees C affects intermediates in the folding pathway rather than the native structure. At temperatures above 60 degrees C the wild-type and mutant forms were distinguishable: the reversible and irreversible denaturation thresholds were approximately 15 to 20 degrees C lower in the mutant than in the wild-type protein. The irreversible denaturation of the mutant tailspikes led to different aggregation/polymerization products from the wild-type, indicating that the mutation altered the unfolding pathway. In both cases only a small percentage of the native secondary structure was altered by irreversible thermal denaturation, indicating that the aggregated states retain considerable native structure.

Glycoside Hydrolases↗
PubMed1987

Phage phi X174 probed by laser Raman spectroscopy: evidence for capsid-imposed constraint on DNA secondary structure.

The Raman spectrum of the isometric bacteriophage phi X174 contains a number of well-resolved bands which have been assigned unambiguously to proteins of the capsid or to the single-stranded DNA (ssDNA) genome. Additional Raman bands of protein and DNA, which are partially overlapped in the spectrum of virus, have been resolution enhanced by Fourier deconvolution to permit improved semiquantitative measurement of spectral intensities and frequencies for structural conclusions. Raman conformation markers indicate that the ssDNA molecule within the capsid contains nucleosides of C2'-endo sugar pucker and anti-glycoside bond orientation, but the nucleic acid backbone lacks the geometry characteristic of B-form DNA. The Raman profile of encapsidated phi X DNA indicates a backbone more similar to heat-denatured DNA than to DNA containing hairpinlike secondary structure. This finding suggests limited interbase interactions in the packaged genome, which is presumably the result of constraints imposed by the viral capsid. Thus, the extensive pairing and stacking of bases indicated by Raman profiles from ssRNA viruses are not evident for the phi X174 chromosome. Overall, the proteins of the virion contain extensive beta-sheet and irregular secondary structures. Fourier deconvolution of the Raman amide I band provides an estimate of the percentage of total beta-sheet structure (approximately 60%) in all proteins of the virion. The amide III region of the spectrum confirms that beta-sheet and irregular domains are the predominant protein secondary structures. Samples of phi X174 concentrated for Raman spectroscopy by either ultracentrifugation or ultrafiltration exhibit nearly identical Raman spectra, indicating that either method can be employed to prepare intact virus without significant loss of DNA or protein components.

Bacteriophage phi X 174↗
PubMed1985

Pulmonary vasculitis complicating ulcerative colitis.

Pulmonary vasculitis is an infrequent complication of ulcerative colitis. The patient reported herein had biopsy-proven pulmonary vasculitis on two occasions, associated with flares in ulcerative colitis. The diagnosis of this entity is best made by open lung biopsy. Corticosteroid therapy appears to be a rational first step in the management of this condition.

Adolescent↗
PubMedDate not supplied

Behavioral effects of prenatal and adult exposure to toxic chemicals found in Lake Ontario fish: two methodological approaches.

Two research approaches are described that were used to determine behavioral changes following a diet of Lake Ontario fish. Approach 1 involved the correlational method, in which human subjects voluntarily ate contaminated Lake Ontario fish. Demographic information, data on the amount of Lake Ontario fish consumed, and control variables were obtained during an interview. Respondents' behavior, as well as the behavior of their children, then was measured. Because subjects were not assigned randomly to eat or not eat Lake Ontario fish, other variables that might have influenced both consumption of fish and behavior had to be considered. Therefore, confounding variables were measured and their influence controlled for using statistical techniques. Approach 2 involved the experimental method using laboratory rats, where subjects were assigned randomly to receive a diet of environmentally contaminated Lake Ontario salmon, relatively uncontaminated Pacific Ocean salmon, or no salmon. Since the rats fed Lake Ontario salmon behaved differently than the other two groups on nine tasks, it was concluded that the contaminants in Lake Ontario salmon caused behavioral changes. Random assignment of subjects to groups eliminated competing explanations. If similar behavioral (e.g., emotional or cognitive) results were obtained using the two approaches, then the results utilizing rats probably could be generalized to humans, and the correlational results found in humans probably were due to a cause and effect relationship.

Animals↗
PubMedDate not supplied

Maternal consumption of Lake Ontario salmon in rats produces behavioral changes in the offspring.

The current study assessed the effects of maternal, paternal, or combined parental consumption of Lake Ontario salmon in rats on the behavior of their offspring. Adult female Sprague-Dawley rats were put on a 30 day diet of either ground rat chow containing 30% Lake Ontario salmon (LAKE) or 30% Pacific Ocean salmon (OCEAN). These females were then mated with adult male rats similarly exposed (LAKE or OCEAN). An additional control group of males and females who were fed ground rat chow (MASH) only were also mated. These pairing combinations resulted in five offspring groups: LAKE-LAKE, LAKE-OCEAN, OCEAN-LAKE, OCEAN-OCEAN, MASH-MASH. When the offspring reached 80 days of age, they were tested for reactivity to frustrative nonreward using runway successive negative contrast, which has been repeatedly shown to be increased in adult rats fed Ontario salmon. Consistent with previous work, results showed that the behavior of the OCEAN-OCEAN rats did not differ from the MASH-MASH group, indicating that a salmon diet per se does not cause behavioral change. However, the offspring of dams who consumed Lake Ontario salmon (LAKE-LAKE and OCEAN-LAKE) showed an increased depression effect relative to controls. There was little evidence of a paternal effect. A follow-up experiment employed cross-fostering to determine the relative contribution of pre- and/or postnatal exposure to Lake Ontario salmon consumption on offspring behavior. Rat pups were cross-fostered to or from dams who consumed Lake Ontario salmon during gestation and parturition. Results from two separate replications indicated that prenatal (LAKE to OCEAN) exposure alone or postnatal (OCEAN to LAKE) exposure alone produced a large increase in successive negative contrast relative to controls (OCEAN to OCEAN). These data are strong evidence of behavioral changes produced by maternal consumption of Lake Ontario salmon in the offspring rat. Further, they indicate that either prenatal or postnatal exposure alone is sufficient to produce behavioral changes in the offspring.

Animals↗