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Biomedical subjects

M A Turner

Publications and source records attributed to M A Turner.

At least 19 recordsLinked to original sources
PubMed1998

Bioaccumulation of radionuclides in fertilized Canadian Shield lake basins.

Radionuclide tracers of heavy metals (59Fe, 60Co, 65Zn, 75Se, 85Sr, 134Cs and 203Hg) representing potential contamination from nuclear power plants, industry and agriculture were added to separate basins of Lake 226, Experimental Lakes Area, northwestern Ontario. The two basins were part of a eutrophication experiment and differed in their trophic status; the north basin (L226N) was eutrophic whereas the south basin (L226S) was mesotrophic. Our objective was to determine the uptake of the radionuclides by biota and the effect of lake trophic status on their bioaccumulation. The trophic status of the lakes did not appear to have a marked effect on the accumulation of radionuclides by the biota. This may have been because of a mid-summer leakage of nutrients between the basins which enhanced primary production in L226S, because there is a time lag between primary production and the availability of the radionuclides to the fishes or because trophic status does not affect the uptake of at least some of these radionuclides. However, there was a tendency for faster uptake of the radionuclides in L226N by fish than L226S, but the differences were not significant. Concentrations in the biota generally decreased in the order: fathead minnow > pearl dace > tadpoles > slimy sculpin > leeches. Concentrations in biota generally decreased in the order. 65Zn > 203Hg > 75Se > 134Cs > 60Co > 85Sr = 59Fe. Cobalt-60 concentrations in tadpoles were greater than in the other biota. Radionuclide concentrations in the tissues of lake whitefish indicated that uptake was predominantly from food. Radionuclide concentrations were usually higher in the posterior gut, liver and kidney than in other tissues, whereas body burdens were generally high in the muscle for 75Se, 134Cs and 203Hg; kidney and gut for 60Co; and bone for 65Zn and 75Se. Mercury-203 burdens were also high in the bone and gut.

Agriculture↗
PubMed1998

Intragenic complementation at the argininosuccinate lyase locus: reconstruction of the active site.

Intragenic complementation has been observed at the argininosuccinate lyase (ASL) locus and the ASL alleles in the ASL-deficient cell strains of two complementation phenotypes have been identified. The frequent complementers, strains that participate in the majority of the complementation events, were found to be either homozygous or heterozygous for the Q286R allele, while the high-activity complementers, those strains in which complementation is associated with a high restoration of activity, were found to be either homozygous or heterozygous for the D87G allele. Direct proof of the intragenic complementation observed at the ASL locus has been obtained with the co-expression of the D87G and Q286R alleles in COS cells. A significant increase in the ASL activity was observed when the two alleles were co-expressed relative to the expression of each mutant allele alone. The increase in activity was comparable to that observed previously in the fibroblast complementation studies. The structure determinations of ASL and the homologous eye lens protein, duck delta II crystallin, have revealed that the active site of ASL is made up of residues from three different monomers. The structural mapping of the Q286 and D87 residues shows that both are located near the active site but that, in any one active site, each is contributed by a different monomer. The molecular symmetry of the ASL protein is such that when mutant monomers combine randomly, one active site will contain both mutations and at least one active site will contain no mutations at all. It is these 'native' active sites in the hybrid Q286R/D87G proteins that give rise to the partial recovery of enzymatic activity observed during intragenic complementation.

Animals↗
PubMed1998

Structure determination of selenomethionyl S-adenosylhomocysteine hydrolase using data at a single wavelength.

S-Adenosylhomocysteine (AdoHcy) hydrolase regulates all adenosylmethionine-(AdoMet) dependent transmethylations by hydrolyzing the potent feedback inhibitor AdoHcy to homocysteine and adenosine. The crystallographic structure determination of a selenomethionyl-incorporated AdoHcy hydrolase inhibitor complex was accomplished using single wavelength anomalous diffraction data and the direct methods program, Snb v2.0, which produced the positions of all 30 crystallographically distinct selenium atoms. The mode of enzyme-cofactor binding is unique, requiring interactions from two protein monomers. An unusual dual role for a catalytic water molecule in the active site is revealed in the complex with the adenosine analog 2'-hydroxy, 3'-ketocyclopent-4'-enyladenine.

Adenosylhomocysteinase↗
PubMed1998

Half-Fourier RARE MR cholangiopancreatography: experience in 300 subjects.

PURPOSE: To determine prospectively the clinical applications and diagnostic accuracy of half-Fourier rapid acquisition with relaxation enhancement (RARE) magnetic resonance (MR) cholangiopancreatography (MRCP) in a large patient population. MATERIALS AND METHODS: Breath-hold, heavily T2-weighted half-Fourier RARE MRCP was performed in 265 patients with suspected pancreaticobiliary disease and in 35 control patients without symptoms or signs referrable to the biliary tract or pancreatic duct. MRCP findings were correlated with those at direct cholangiography, pathologic examination, cross-sectional imaging, and clinical follow-up. RESULTS: Diagnostic MRCP examinations were obtained in 299 (99.7%) subjects. MRCP yielded an accuracy of 100% in determining the presence of pancreaticobiliary disease, the presence and level of biliary obstruction, and obstruction due to bile duct calculi. The accuracy of MRCP and MR imaging in determining the presence and level of malignant obstruction was 98.2%. MRCP obviated endoscopic retrograde cholangiopancreatography (ERCP) by excluding choledocholithiasis in patients with acute pancreatitis (n = 13) and nonspecific abdominal pain (n = 82). In patients with sclerosing cholangitis and acquired immunodeficiency syndrome cholangiopathy, MRCP depicted the biliary tract as clearly as did ERCP (n = 9). After failed ERCP, MRCP delineated the pancreaticobiliary tract and helped determine therapeutic options (n = 27). CONCLUSION: Half-Fourier RARE MRCP enables accurate evaluation of pancreaticobiliary disease and obviates ERCP in some patients.

Adolescent↗
PubMed1998

Adjustable laparoscopic gastric band for the treatment of morbid obesity: radiologic evaluation.

OBJECTIVE: This article describes the radiographic appearance of a recently developed laparoscopically placed adjustable gastric band for the treatment of morbid obesity. The optimal technique for contrast evaluation of the device, complications associated with its use, and the technique for stoma adjustments are also discussed. SUBJECTS AND METHODS: Between May and December 1996, 23 patients at our institution underwent laparoscopic placement of adjustable silicone gastric bands for treatment of morbid obesity. All patients underwent a barium upper gastrointestinal series before surgery, 1 day after band placement, at variable intervals when each patient returned for band adjustment, and at 1 year. RESULTS: Unlike the case in other gastric weight loss procedures, the optimal patient position for contrast evaluation of gastric bands was anteroposterior or slightly right posterior oblique. Twenty-one of 23 patients had no complications shown on the postoperative upper gastrointestinal series. Stoma size was approximately 3-8 mm, and most patients showed delayed esophageal emptying without obstruction. Two patients had herniation of the stomach through the gastric band with pouch enlargement, resulting in obstruction and the need for additional surgery. We saw no leaks or band erosions. Nineteen stoma adjustments were performed in 13 patients. One patient had an inverted port that could not be accessed for adjustment. CONCLUSION: As adjustable gastric bands become more widely used, radiologists need to be familiar with the radiographic appearance of the devices, the complications associated with their use, and the optimal patient positioning for contrast evaluation. Radiologists may also be involved with band adjustment to decrease or increase the stoma size and therefore need to understand the technique and potential difficulties of adjusting the stoma.

Adult↗
PubMed1998

Magnetic resonance cholangiopancreatography: a new technique for evaluating the biliary tract and pancreatic duct.

Magnetic resonance cholangiopancreatography (MRCP) represents a new development in MR technology that provides a noninvasive accurate means of evaluating the biliary tree and pancreatic duct. Recent technical refinements that allow for imaging of the entire biliary tree and pancreatic duct in 18 seconds make this examination easily performed even in critically ill patients. The clinical applications of MRCP are illustrated in a variety of scenarios that include choledocholithiasis, malignant obstruction, incomplete/failed endoscopic retrograde cholangiopancreatographies (ERCPs), postsurgical alterations of the biliary tract and gastrointestinal tract such as biliary-enteric anastomoses, intrahepatic bile duct pathology such as sclerosing cholangitis and AIDS cholangiopathy, chronic pancreatitis, congenital anomalies of the biliary tract and pancreatic duct, and gallbladder pathology.

Bile Duct Diseases↗
PubMed1997

Structural comparison of the enzymatically active and inactive forms of delta crystallin and the role of histidine 91.

The major soluble protein component of avian and reptilian eye lenses, delta crystallin, is highly homologous to the urea cycle enzyme, argininosuccinate lyase (ASL). In duck lenses there are two highly homologous delta crystallins, termed delta I and delta II, that are 94% identical in amino acid sequence. While delta II crystallin has been shown to exhibit ASL activity in vitro, delta I crystallin is inactive. The X-ray structure of a His to Asn mutant of duck delta II crystallin (H91N) has been determined to 2.5 A resolution using the molecular replacement technique. The overall fold of the protein is similar to other members of the superfamily to which this protein belongs, with the active site located in a cleft between three different monomers of the tetrameric protein. A reexamination of the kinetic properties of the H91N mutant reveals that the mutant has 10% wild-type activity. The Vmax of the mutant protein is identical to that of the wild-type protein, but a 10-fold increase in the Michaelis constant is seen, suggesting that His 91 is involved in binding the substrate. In an effort to determine the reasons for the loss of enzymatic activity in delta I crystallin, a structural comparison of the H91N mutant with the enzymatically inactive turkey delta I crystallin has been performed. This study revealed a remarkable similarity in the overall structures of the two proteins. Three regions of secondary structure do differ significantly between the two models; these include the N-terminal tail, a loop containing residues 76-91, and a cis versus trans peptide linkage at residue Thr 322. The cis to trans peptide variation appears to be an interspecies difference between turkey and duck and is therefore not directly involved in the loss of enzymatic activity. All the residues implicated in the catalytic mechanism are conserved in both the active and inactive proteins, and given the linearity of the relationship between the enzymatic activity of duck delta I/delta II heterotetramers and their delta II content (Piatigorsky & Horwitz, 1996), it is evident from the structure that only one of the three domains that contributes to the active site is responsible for the loss of activity in the delta I protein. Given the structural differences found in domain 1 (N-terminal tail and 76-91 loop), we postulate that these differences are responsible for the loss of catalytic activity in the delta I crystallin protein and that the delta I protein is inactive because it no longer binds the substrate.

Amino Acid Sequence↗
PubMed1997

Human argininosuccinate lyase: a structural basis for intragenic complementation.

Intragenic complementation has been observed at the argininosuccinate lyase (ASL) locus. Intragenic complementation is a phenomenon that occurs when a multimeric protein is formed from subunits produced by different mutant alleles of a gene. The resulting hybrid protein exhibits enzymatic activity that is greater than that found in the oligomeric proteins produced by each mutant allele alone. The mutations involved in the most successful complementation event observed in ASL deficiency were found to be an aspartate to glycine mutation at codon 87 of one allele (D87G) coupled with a glutamine to arginine mutation at codon 286 of the other (Q286R). To understand the structural basis of the Q286R:D87G intragenic complementation event at the ASL locus, we have determined the x-ray crystal structure of recombinant human ASL at 4. 0 A resolution. The structure has been refined to an R factor of 18. 8%. Two monomers related by a noncrystallographic 2-fold axis comprise the asymmetric unit, and a crystallographic 2-fold axis of space group P3121 completes the tetramer. Each of the four active sites is composed of residues from three monomers. Structural mapping of the Q286R and D87G mutations indicate that both are near the active site and each is contributed by a different monomer. Thus when mutant monomers combine randomly such that one active site contains both mutations, it is required by molecular symmetry that another active site exists with no mutations. These "native" active sites give rise to the observed partial recovery of enzymatic activity.

Alleles↗
PubMed1997

Molecular characterization of the prokaryotic efp gene product involved in a peptidyltransferase reaction.

The translation factor EF-P is required for efficient prokaryotic peptide bond synthesis on 70S ribosomes from fMet-tRNAfMet. This protein has been purified from Escherichia coli cells and the gene, efp, encoding it has been cloned and sequenced. We have isolated recombinant clones which overexpress a protein that co-migrates with purified EF-P upon SDS-PAGE analysis. Using these clones, we report the purification, crystallization and initial characterization of the efp gene product. The mechanism by which EF-P stimulates peptide-bond synthesis was studied using several antibiotics that inhibit translocation, peptide-bond synthesis and decoding. The stimulation of peptidyltransferase by EF-P was not inhibited by antibiotics that affect translocation and occupation of the A site (in the elongation state), ie thiostrepton, viomycin, neomycin and fusidic acid but was inhibited by streptomycin as well as by inhibitors of peptidyltransferase, chloramphenicol and lincomycin. This observation and the requirement for L16 but not for the L7/L12 nor L6 or L11 r-proteins suggest that the binding site for EF-P may overlap the peptidyltransferase center of the ribosome.

Anti-Bacterial Agents↗
PubMed1997

Epithelial-stromal interactions modulating penetration of matrigel membranes by HPV 16-immortalized keratinocytes.

The role of epithelial-stromal interactions in the progression of human papillomavirus-associated squamous intraepithelial lesions to invasive cervical cancer is poorly understood. Using the Matrigel artificial basement membrane assay as a model of keratinocyte invasion, the effects of selected growth factors on penetration of human papillomavirus 16-immortalized keratinocytes through Matrigel were studied. Also studied in this model were the effects of conditioned media from fibroblast lines derived from normal cervical tissues (normal fibroblasts) and adjacent cervical cancer biopsies (tumor-associated fibroblasts) and from primary keratinocytes. Addition of basic fibroblast growth factor, transforming growth factor-alpha, and hepatocyte growth factor/scatter factor or conditioned media from tumor-associated fibroblasts to the Matrigel resulted in near-doubling of penetration of human papillomavirus 16-immortalized keratinocytes, whereas transforming growth factor-beta, platelet derived growth factor-B, or conditioned media from primary keratinocytes decreased penetration 10-fold. Antibodies to basic fibroblast growth factor abrogated the stimulatory effects of conditioned media from tumor-associated fibroblasts on keratinocyte penetration, whereas antibodies to transforming growth factor-beta abrogated the inhibitory effects of conditioned media from normal fibroblasts on keratinocyte penetration. S1 nuclease protection and enzyme-linked immunosorbent assay showed increased expression of transforming growth factor-beta and decreased expression of basic fibroblast growth factor in normal compared with tumor-associated fibroblasts. Messenger RNA in situ hybridization of five cervical cancer biopsies demonstrated basic fibroblast growth factor expression in stromal cells surrounding nests of invading keratinocytes. Epithelial-stromal interactions mediated by growth factors such as transforming growth factor-beta and basic fibroblast growth factor modulate penetration of human papillomavirus 16-immortalized keratinocytes through Matrigel in vitro and these interactions may also be operative in vivo.

Basement Membrane↗
PubMed1997

HASTE MR cholangiography in the evaluation of hilar cholangiocarcinoma.

OBJECTIVE: The objective of this study was to determine the usefulness of MR cholangiography using the half-Fourier acquisition single-shot turbo spin-echo sequence in the examination of patients with hilar cholangiocarcinoma. CONCLUSION: Half-Fourier acquisition single-shot turbo spin-echo MR cholangiography is a useful, noninvasive adjunct to other imaging techniques, particularly MR imaging, in the evaluation of hilar cholangiocarcinoma. MR cholangiography allows rapid visualization of the biliary tract without instrumentation and, therefore, without the risk of inducing sepsis in a patient with ductal obstruction. In the six patients presented. MR cholangiography allowed for determination of the proximal extent of disease and assessment of resectability and delineated the duct both proximal and distal to the stricture and isolated ductal obstructions. MR cholangiography provides three-dimensional images of the biliary tract that facilitate planning of surgery, palliative drainage, and radiation therapy.

Aged↗
PubMed1996

Nutrition measures for managed care report cards.

Health plan "report cards," that is, published summaries of health plan performance, are a new way to help consumers select a health plan on the basis of cost and quality. The Health Plan Employer Data and Information Set (HEDIS) includes a set of health plan performance measures, standardized definitions, and methods for data collection. HEDIS is used as the basis for many report card initiatives and is the preferred tool of the managed care industry for measuring health plan performance. Nevertheless, the current list of HEDIS performance measures omits many health services, including medical nutrition therapy. Nutrition measures have the potential for wide appeal among health care stakeholders (ie, payers, consumers, and providers). Four measures related to medical nutrition therapy are proposed for managed care report cards: staffing for nutrition services and medical nutrition therapy for high cholesterol level, gestational diabetes, and cardiovascular disease. Barriers to adopting medical nutrition therapy measures in HEDIS include the need to address technical issues before considering new measures and competition from other potential measures. Steps to create support for medical nutrition therapy measures in HEDIS should focus on influencing representatives of health plans and employers to include these measures. The involvement of registered dietitians in the dynamic process of health plan evaluation is an important extension of ongoing efforts for strategic positioning in the managed care market.

Dietary Services↗
PubMed1996

Gastrointestinal tract involvement by gynecologic diseases.

Involvement of the gastrointestinal tract by gynecologic disease processes-endometriosis, gynecologic neoplasms, inflammatory processes, and complications from radiation therapy or surgery for gynecologic tumors-may mimic primary gastrointestinal carcinoma on radiologic images. Endometriosis most often involves the anterior wall of the rectosigmoid colon, adjacent to the pouch of Douglas, and typically produces extrinsic mass effect on the serosa, with the overlying mucosa left intact. Direct extension of ovarian cancer to the colon through the subperitoneal space produces mass effect with serosal spiculation, tethering, and fixation; annular constriction; or partial or complete obstruction. Intraperitoneal seeding of ovarian carcinoma most frequently involves the colon and is seen as extrinsic masses, often with serosal spiculation and tethering. Cervical carcinoma, which most commonly spreads by direct invasion of the pelvic side wall and adjacent structures, produces serosal spiculation and circumferential narrowing. Benign ovarian or uterine tumors are purely extrinsic and have a smooth interface with the colonic wall. Tubo-ovarian abscesses are difficult to differentiate from cystic ovarian neoplasms or endometriomas. Radiation colitis causes narrowing of the rectum with intact mucosa and can be differentiated from recurrent tumor, unlike radiation-induced injury of the small bowel, which may be difficult to distinguish. Surgical adhesions produce a discrete transition point between dilated bowel proximally and nondilated distal bowel. Familiarity with the varied patterns of gastrointestinal tract involvement is important for accurate interpretation of imaging studies.

Diagnosis, Differential↗
PubMed1996

Percutaneous drainage of enteric-related abscesses.

Percutaneous drainage is a routinely performed radiologic procedure used in the management of abdominal abscesses. This technique has become the preferred method of treatment for most abdominal and pelvic abscesses, specifically those of enteric origin related to surgical procedures, appendicitis, diverticulitis, and Crohn disease. The well-documented safety and therapeutic efficacy of percutaneous abscess drainage (PAD) lead to the acceptance of this procedure as the primary means of managing abdominal abscesses, obviating the need for surgery in many instances. PAD may provide definitive therapy or may serve as a temporizing measure before delayed surgical treatment. Although PAD was originally reserved for treatment of unilocular, relatively superficial fluid collections, the role of PAD has evolved such that it is now used to manage complex multilocular fluid collections and abscesses that lie deep within the abdomen or pelvis. Although the standard transabdominal approach is preferred, a variety of approaches, including transgastric, transrectal, transvaginal, and transgluteal, may be used. PAD is performed using CT or sonographic guidance.

Abdominal Abscess↗
PubMed1995

Structures of partridge egg-white lysozyme with and without tri-N-acetylchitotriose inhibitor at 1.9 A resolution.

The three-dimensional structures of native partridge egg-white lysozyme (PEWL) and PEWL complexed with tri-N-acetylchitotriose inhibitor have been determined crystallographically and refined at 1.9 A resolution. Crystals of native and complexed protein are isomorphous and have space group and cell dimensions that are identical to those of hen egg-white lysozyme (HEWL) under similar crystallization conditions. Full occupancy of the trisaccharide in the inhibitor complex has allowed definitive modeling and refinement of all three sugar residues, located at subsites A, B, and C in the PEWL active site. A comparison has been made with HEWL/inhibitor complexes in which coordinates were either not refined (Blake CCF, et al., 1967, Proc R Soc B 167:378-388) or were refined at partial occupancy (Cheetham JC, Artymiuk PJ, Phillips DC, 1992, J Mol Biol 224:613-628). Although the loop comprising residues 70-75 is located on the surface of the protein and not near the active site, it appears to be affected indirectly by trisaccharide binding such that the loop shifts toward the active site and becomes relatively immobilized. The source of this loop movement appears to be the anchoring of Trp62, located in the active site cleft, as it forms a hydrogen bond with O6 of the N-acetylglucosamine at site C. Good electron density for the trisaccharide in the PEWL complex structure shows that Asp 101 is involved in hydrogen bonding interactions with the terminal sugar residue.

Animals↗
PubMed1995

Urokinase plasminogen activator expression by primary and HPV 16-transformed keratinocytes.

The molecular events underlying progression of human papillomavirus (HPV) 16-associated intraepithelial neoplasia to invasive cancer have not been studied in detail. Penetration of the basement membrane is an early, but poorly understood step in this process and probably involves the action of one or more metallo- and serine proteinases. Urokinase-type plasminogen activator (uPA) is a serine proteinase that has been implicated in the pathogenesis of several epithelial tumors, but its role in HPV-associated tumors is not known. To examine uPA expression by HPV 16-transformed keratinocytes in vitro, primary foreskin keratinocyte cultures were transfected by HPV 16 DNA. The primary parental cells and the HPV 16-transformed keratinocytes were studied using substrate gel zymography, Western blot analysis and an in vitro assay measuring penetration of a Matrigel artificial basement membrane. Both uPA and its inhibitor, plasminogen activator inhibitor-1 (PAI-1), were overexpressed in the HPV 16-transformed cells relative to the parental cell line. The transformed cells, but not the parental cells, were able to degrade and penetrate the Matrigel membrane and penetration was blocked by both PAI-1 and by antibodies to uPA. Our data suggest that HPV 16-induced transformation of keratinocytes is associated with upregulation of uPA expression. In conjunction with other proteinases, uPA plays an important role in the ability of HPV 16-transformed keratinocytes to penetrate artificial basement membranes.

Basement Membrane↗