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A Coker

Publications and source records attributed to A Coker.

At least 37 records · Page 2Linked to original sources
PubMed1999

X-ray structure of 5-aminolevulinic acid dehydratase from Escherichia coli complexed with the inhibitor levulinic acid at 2.0 A resolution.

5-Aminolevulinic acid dehydratase (ALAD), an early enzyme of the tetrapyrrole biosynthesis pathway, catalyzes the dimerization of 5-aminolevulinic acid to form the pyrrole, porphobilinogen. ALAD from Escherichia coli is shown to form a homo-octameric structure with 422 symmetry in which each subunit adopts the TIM barrel fold with a 30-residue N-terminal arm. Pairs of monomers associate with their arms wrapped around each other. Four of these dimers interact, principally via their arm regions, to form octamers in which each active site is located on the surface. The active site contains two lysine residues (195 and 247), one of which (Lys 247) forms a Schiff base link with the bound substrate analogue, levulinic acid. Of the two substrate binding sites (referred to as A and P), our analysis defines the residues forming the P-site, which is where the first ALA molecule to associate with the enzyme binds. The carboxyl group of the levulinic acid moiety forms hydrogen bonds with the side chains of Ser 273 and Tyr 312. In proximity to the levulinic acid is a zinc binding site formed by three cysteines (Cys 120, 122, and 130) and a solvent molecule. We infer that the second substrate binding site (or A-site) is located between the triple-cysteine zinc site and the bound levulinic acid moiety. Two invariant arginine residues in a loop covering the active site (Arg 205 and Arg 216) appear to be appropriately placed to bind the carboxylate of the A-site substrate. Another metal binding site, close to the active site flap, in which a putative zinc ion is coordinated by a carboxyl and five solvent molecules may account for the activating properties of magnesium ions.

Binding Sites↗
PubMed1999

The Schiff base complex of yeast 5-aminolaevulinic acid dehydratase with laevulinic acid.

The X-ray structure of the complex formed between yeast 5-aminolaevulinic acid dehydratase (ALAD) and the inhibitor laevulinic acid has been determined at 2.15 A resolution. The inhibitor binds by forming a Schiff base link with one of the two invariant lysines at the catalytic center: Lys263. It is known that this lysine forms a Schiff base link with substrate bound at the enzyme's so-called P-site. The carboxyl group of laevulinic acid makes hydrogen bonds with the side-chain-OH groups of Tyr329 and Ser290, as well as with the main-chain >NH group of Ser290. The aliphatic moiety of the inhibitor makes hydrophobic interactions with surrounding aromatic residues in the protein including Phe219, which resides in the flap covering the active site. Our analysis strongly suggests that the same interactions will be made by P-side substrate and also indicates that the substrate that binds at the enzyme's A-site will interact with the enzyme's zinc ion bound by three cysteines (133, 135, and 143). Inhibitor binding caused a substantial ordering of the active site flap (residues 217-235), which was largely invisible in the native electron density map and indicates that this highly conserved yet flexible region has a specific role in substrate binding during catalysis.

Binding Sites↗
PubMed1999

Angiogenesis and p53 and H-ras mutations in pancreatic ductal adenocarcinoma.

OBJECTIVE: To evaluate the correlation of angiogenesis and p53 and H-ras mutations with prognostic factors and proliferative activity assessed with Ki-67 protein expression by studying archival tissues from 24 patients with primary pancreatic ductal adenocarcinoma. STUDY DESIGN: Vascular structures were labeled immunohistochemically using factor VIII-related antigen. Vascular surface density (VSD) and microvessel number (NVES) were assessed by stereology. The tissues were also analyzed with the immunohistochemical method for the expression of proteins, including p53, H-ras and Ki-67. RESULTS: Statistical analysis revealed that tumors with greater NVES and VSD values significantly correlated with occurrence of metastases, higher proliferative activity, poorer histologic differentiation and greater tumor size. p53 Mutations were found in 11 cases (45.8%). However, only three cases (12.5%), all negative for p53 mutations, showed H-ras mutations. p53 Mutation-positive tumors exhibited a statistically significant correlation with occurrence of metastases and higher proliferative activity, whereas H-ras mutations did not show such a correlation. CONCLUSION: Angiogenesis might have a role in predicting prognosis in pancreatic carcinomas, and p53 mutations might be acquired in later stages associated with metastatic progression and higher proliferative activity. Although H-ras mutations were rare in the present study, they might play a role in a different carcinogenic pathway excluding p53 mutations.

Adult↗
PubMed1998

PRFLL--a Pinus radiata homologue of FLORICAULA and LEAFY is expressed in buds containing vegetative shoot and undifferentiated male cone primordia.

In angiosperms, the formation of the flower meristem is controlled by partially redundant flower meristem identity genes of which FLORICAULA (FLO)/LEAFY (LFY) plays a central role. It is not known whether formation of reproductive organs of pre-angiosperm species is similarly regulated. Recently, a FLO/LFY-like cDNA, NEEDLY (NLY), has been cloned in a conifer species Pinus radiata (D. Don). Here we report cloning of a different Pinus radiata FLO/LFY-like cDNA, PRFLL. PRFLL had two large regions of high similarity to angiosperm FLO/LFY orthologues: amino acids 61-126 and 247-406 (50% and 81% identity, and 75% and 88% similarity, respectively, to LFY) and shorter regions of local similarity. Overall identity was 53% to LFY and 61% to NLY. Phylogenetic analysis of deduced protein sequences including partial LFY-like sequences from Pseudotsuga menziesii indicated that conifer proteins constituted a separate clade that could be divided into two groups represented by NLY and PRFLL. In contrast to angiosperms, both conifers had two paralogous proteins resembling LFY. Northern hybridisation analysis revealed expression of PRFLL in vegetative buds of juvenile, adolescent and mature trees. The transcript was not detected in vascular cambium, roots or secondary needles. To follow PRFLL expression during the early stages of cone development we analysed a temporal series of buds containing cone primordia, and developing cones, using Northern hybridisation and confocal microscopy in parallel. PRFLL mRNA was detected in buds from dominant and subordinate branches, in which cone and shoot primordia develop, and in developing male cones but not in developing female cones. Expression was particularly high in buds containing axillary primordia prior to their differentiation as male cone primordia. This is consistent with PRFLL being involved in determination of the male cone primordium identity.

Amino Acid Sequence↗
PubMed1997

The B-Lynch surgical technique for the control of massive postpartum haemorrhage: an alternative to hysterectomy? Five cases reported.

The B-Lynch suturing technique (brace suture) may be particularly useful because of its simplicity of application, life saving potential, relative safety, and its capacity for preserving the uterus and thus fertility. Satisfactory haemostasis can be assessed immediately after application. If it fails, which has not yet been the case, other more radical surgical methods as mentioned in this paper and in the literature can be considered. The special advantage of this innovative technique is an alternative to major surgical procedures to control pelvic arterial pulse pressure or hysterectomy. This suturing technique has been successfully applied with no problems to date and no apparent complications.

Abruptio Placentae↗
PubMed1996

Loss of hIRH mRNA expression from premalignant adenomas and malignant cell lines.

We recently isolated from differential displays and subsequently cloned a human alpha-intercrine (hIRH) whose mRNA is reduced in human hepatocellular carcinomas. We now report that on Northern blots its mRNA is absent from premalignant colonic adenomas and from all of 27 human malignant cell lines (including breast, cervix, colon, duodenal, gastric, leukemia, liver, lung, melanoma, and pancreatic lines). hIRH mRNA was present in most normal human and mouse tissues and fibroblast derived cell lines but absent from leukocytes and brain. Two mRNA signals, at approximately 2 Kb and approximately 3.5 Kb, had variation in signal strength or size between tissues and species.

Adenoma↗
PubMed1996

A clinical analysis of 500 medico-legal claims evaluating the causes and assessing the potential benefit of alternative dispute resolution.

OBJECTIVE: 1. To evaluate the common causes of medico-legal dispute in obstetrics and gynaecology. 2. To assess the potential benefit of early alternative dispute resolution. DESIGN: A prospective analysis of over 500 cases submitted from over 100 solicitors between 1984 and 1994 for medical expert opinion on potential medico-legal claims. CASES: Five hundred consecutive cases that met the inclusion criteria: 488 from the United Kingdom and 12 from abroad (Hong Kong, Republic of Ireland). MAIN OUTCOME MEASURES: The main principles underlining medico-legal disputes and causes of such claims. RESULTS: Analysis of 500 claims show 46% were misguided allegations, 19% incompetent care, 12% error of judgement, 9% lack of expertise, 7% failure of communication, 6% poor supervision and 1% inadequate staffing. Of the misguided allegations 119/225 cases (59%) were obstetric and 111/275 (40%) cases were gynaecological. The most common cause of obstetric dispute was "cerebral palsy' (22%), while the commonest cause of gynaecological dispute was failed sterilisation (19%). Settled claims were under-reported by solicitors. CONCLUSION: Because of the high percentage (46%) of misguided allegations, an alternative course of dispute resolution must be a realistic way forward. This course of action, combined with improved communication, could result in a major reduction in the costs of potential medical litigation. Early alternative dispute resolution should be considered in an attempt to reduce the escalating quantum of damages and costs. We recommend recruiting independent, experienced and unbiased consultants in active practice within the appropriate specialty to review such cases at the level of hospital complaints management as an in house review procedure, particularly for small and moderate-sized claims, as a means whereby doctors can retain control of medico-legal disputes, in contrast to control by the legal profession.

Adolescent↗
PubMed1993

The acute effects of pancreaticopyelostomy on the pancreas and kidney. A preliminary study.

A modified canine pancreaticopyelostomy model with an intact kidney was constructed. The effects of this procedure on the pancreas and kidney were examined in five dogs by monitoring the serum and urine levels of pH, bicarbonate, chloride, glucose, urea, creatinine and amylase in 24-h periods for up to 72 h. The contralateral kidney served as controls. The pancreas and kidney were removed and examined under light microscopy after the animals were sacrificed. Both of the organs had maintained their normal histological architecture. The serum and urine glucose levels were consistent with a normal response after the initial elevation immediately following the surgical trauma. The urine urea concentrations from both kidneys were similar, as were the creatinine excretion trends throughout the 72 h, except for a significant rise in the creatinine excretion on the pancreaticopyelostomy side at 24 h. The pH, bicarbonate, chloride, and amylase values revealed a normal and functioning exocrine pancreas. It is concluded from this preliminary study that pancreaticopyelostomy with an intact kidney does not have acute adverse effects, either on the pancreas or on the kidney. This procedure may be an alternative method for pancreatic exocrine drainage if similar results are obtained in chronic models.

Amylases↗
PubMed1993

Omentoplasty versus introflexion for hydatid liver cysts.

Forty-three patients with unilocular hydatid cyst of the liver were divided into three groups. Omentoplasty (n = 15) was performed in group 1, introflexion (n = 18) in group 2 and a combination of both (n = 10) in group 3. Patients with omentoplasty developed fewer complications and had a significantly shorter hospitalization than those with introflexion. The results indicate that omentoplasty is superior both to introflexion and to introflexion plus omentoplasty for the management of hydatid liver cysts.

Adolescent↗