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Biomedical subjects

C Luke

Publications and source records attributed to C Luke.

13 recordsLinked to original sources
PubMed2000

Circulating serpin tumor markers SCCA1 and SCCA2 are not actively secreted but reside in the cytosol of squamous carcinoma cells.

An elevation in the circulating level of the squamous-cell carcinoma antigen (SCCA) can be a poor prognostic indicator in certain types of squamous-cell cancers. Total SCCA in the circulation comprises 2 nearly identical, approximately 45 kDa proteins, SCCA1 and SCCA2. Both proteins are members of the high-molecular weight serine proteinase inhibitor (serpin) family with SCCA1 paradoxically inhibiting lysosomal cysteine proteinases and SCCA2 inhibiting chymotrypsin-like serine proteinases. Although SCCA1 and SCCA2 are detected in the cytoplasm of normal squamous epithelial cells, neither serpin is detected normally in the serum. Thus, their presence in the circulation at relatively high concentrations suggests that malignant epithelial cells are re-directing serpin activity to the fluid phase via an active secretory process. Because serpins typically inhibit their targets by binding at 1:1 stoichiometry, a change in the distribution pattern of SCCA1 and SCCA2 (i.e., intracellular to extracellular) could indicate the need of tumor cells to neutralize harmful extracellular proteinases. The purpose of our study was to determine experimentally the fate of SCCA1 and SCCA2 in squamous carcinoma cells. Using subcellular fractionation, SCCA-green fluorescent fusion protein expression and confocal microscopy, SCCA1 and SCCA2 were found exclusively in the cytosol and were not associated with nuclei, mitochondria, lysosomes, microtubules, actin or the Golgi. In contrast to previous reports, metabolic labeling and pulse-chase experiments showed that neither non-stimulated nor TNFalpha/PMA-stimulated squamous carcinoma cells appreciably secreted these ov-serpins into the medium. Collectively, these data suggest that the major site of SCCA1 and SCCA2 inhibitory activity remains within the cytosol and that their presence in the sera of patients with advanced squamous-cell carcinomas may be due to their passive release into the circulation.

Amino Acid Sequence↗
PubMed2000

Simple modifications of the serpin reactive site loop convert SCCA2 into a cysteine proteinase inhibitor: a critical role for the P3' proline in facilitating RSL cleavage.

The human squamous cell carcinoma antigens (SCCA) 1 and 2 are members of the serpin family that are 92% identical in their amino acid sequence. Despite this similarity, they inhibit distinct classes of proteinases. SCCA1 neutralizes the papain-like cysteine proteinases, cathepsins (cat) S, L, and K; and SCCA2 inhibits the chymotrypsin-like serine proteinases, catG and human mast cell chymase. SCCA2 also can inhibit catS, as well as other papain-like cysteine proteinases, albeit at a rate 50-fold less than that of SCCA1. Analysis of the mechanism of inhibition by SCCA1 revealed that the reactive site loop (RSL) is important for cysteine proteinase inhibition. The inhibition of catS by a mutant SCCA2 containing the RSL of SCCA1 is comparable to that of wild-type SCCA1. This finding suggested that there were no motifs outside and only eight residues within the RSL that were directing catS-specific inhibition. The purpose of this study was to determine which of these residues might account for the marked difference in the ability of SCCA1 and SCCA2 to inhibit papain-like cysteine proteinases. SCCA2 molecules containing different RSL mutations showed that no single amino acid substitution could convert SCCA2 into a more potent cysteine proteinase inhibitor. Rather, different combinations of mutations led to incremental increases in catS inhibitory activity with residues in four positions (P1, P3', P4', and P11') accounting for 80% of the difference in activity between SCCA1 and SCCA2. Interestingly, the RSL cleavage site differed between wild-type SCCA2 and this mutant. Moreover, these data established the importance of a Pro residue in the P3' position for efficient inhibition of catS by both wild-type SCCA1 and mutated SCCA2. Molecular modeling studies suggested that this residue might facilitate positioning of the RSL within the active site of the cysteine proteinase.

Amino Acid Sequence↗
PubMed2000

The burden of alcohol misuse on an inner-city general hospital.

Alcohol consumption in the UK has been increasing steadily. We prospectively studied the burden on hospital services caused by overt alcohol misuse, in an inner-city hospital in north-west England. All Accident & Emergency (A&E) patients were assessed to determine whether their hospital attendance was alcohol-related, and whether this resulted in admission and/or generated new out-patient appointments. Over 2 months, 1915 patients attended A&E with alcohol-related problems, accounting for 12% of attendances; 50% were aged 18-39 years, and acute alcohol intoxication was the commonest presenting complaint. Overall, 6.2% of all hospital admissions were due to alcohol-related problems. Over 2800 new out-patient visits were likely to have been generated over an 18-month period from initial attendance with an alcohol-related problem, mostly for orthopaedic clinics. The burden placed by overt alcohol-related problems on hospitals is enormous, both in terms of the emergency and out-patient services. The implementation of education, screening and intervention strategies in A&E departments, and employment of key trained personnel, should be considered, to optimize the clinical management of these patients.

Adolescent↗
PubMed1993

An evaluation of a logbook for trainees in accident & emergency medicine in the United Kingdom: senior consultant opinion.

A previous paper from the Merseyside Group of Senior Registrars in Accident & Emergency Medicine examined the desirability of a logbook for Higher Specialist Training (HST) in accident & emergency medicine in the United Kingdom and its principal ingredients (Luke et al., 1991). A survey of 100 senior registrars and recently appointed consultants in the specialty identified the main issues of importance to the majority of respondents e.g. certification in advanced cardiac and trauma life support, a minimum of three years in the specialty before appointment as senior registrar and certain key secondments. In this paper, more senior consultants in the specialty were surveyed and a resounding majority concurred with the preferences of their junior colleagues. The findings are discussed and the implications for a future curriculum for postgraduate training in A&E medicine are explored.

Attitude of Health Personnel↗
PubMed1991

An evaluation of a logbook for trainees in accident and emergency medicine in the United Kingdom.

The ideal requirements of a logbook for trainees in accident and emergency medicine in the United Kingdom were sought by means of a postal survey of 100 Senior Registrars and recently-appointed Consultants in the specialty. Sixty-two replies were received. An overwhelming majority supported ACLS and ATLS certification, as well as formal training in Management/Clinical Budgeting skills, the use of Information Technology, dealing with medicolegal issues and Disaster Planning. Secondments to General Practice, Regional Poisons Centres and the Emergency Services were similarly recommended. A total of 71% (42 responders) approved of a minimum of 3 years experience in an A&E Department before appointment as a Senior Registrar in the specialty. The majority of responders disapproved of acquiring laboratory-based skills. The results of the survey are discussed and suggestions for the possible role of a logbook are made.

Certification↗
PubMed1989

An audit of trauma deaths occurring in the accident and emergency department.

A retrospective study of all patients who died following trauma in the Accident and Emergency Department of the royal Infirmary of Edinburgh over a 4-year period revealed 50 patients (0.0002% of total attendances). Injury severity scores (ISS) and probabilities of survival (Ps) were calculated for all patients. Two-thirds had a Ps of zero while 7 (14%) had a Ps of 0.5 or more. From the information in the case records and at autopsy four deaths (8%) were considered to have been potentially avoidable on the basis of inadequate or inappropriate management. There were a further eight cases (16%) whose management appeared to have been unsatisfactory but who would have been expected to die even if given optimal treatment. These cases are discussed in detail. Difficulty in diagnosing thoracic injuries and delay in giving appropriate treatment were by far the commonest errors encountered. A protocol for the treatment of patients in cardiorespiratory arrest with thoracic injuries is presented. The importance of regular audit of trauma cases and deaths is emphasized.

Accidents, Traffic↗
PubMedDate not supplied

Weed control.

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England↗