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Biomedical subjects

R Quinlan

Publications and source records attributed to R Quinlan.

At least 19 recordsLinked to original sources
PubMed1998

The chicken CP49 gene contains an extra exon compared to the human CP49 gene which identifies an important step in the evolution of the eye lens intermediate filament proteins.

The gene structure for chicken CP49 gene is presented. It differs from the human CP49 gene with the presence of an extra exon in helix IB and the apparent loss of an intron, intron H. The CP49 gene localises to chromosome 2 in the chicken genome where it is flanked by homologues that map to human chromosome 10p13 (VIM) 6p24-p23 (BMP6). Two transcripts, CP49 and CP49ins, are produced from the single chicken CP49 gene. The difference is a 49-amino-acid insertion in helix IB of CP49 that is encoded by a novel exon found in the chicken CP49 gene. An extended helix IB is believed to be a characteristic of the ancestral intermediate filament protein as it is found in many invertebrate intermediate filament proteins but has been lost from all vertebrate intermediate filament proteins except the nuclear lamins. Although the intron position and length of the helix IB insert sequences in CP49ins differ to those found both in the invertebrate intermediate filament proteins and the vertebrate lamins, the CP49 gene is the first vertebrate cytoplasmic intermediate filament protein to be described with an extended helix IB. The chicken CP49 gene is also the first where differential splicing can remove such a feature. Human and bovine CP49 appear to have lost the helix IB insert sequences, and so the avian CP49 gene provides an interesting evolutionary link between the eye lens proteins and the ancestral intermediate filament protein.

Amino Acid Sequence↗
PubMed1996

Identification of the antigen recognized by the monoclonal antibody BU31 as lamins A and C.

The murine monoclonal antibody BU31 binds to the nuclear membrane of many cell types. The expression of the BU31 antigen has previously been shown to have an inverse correlation with the proliferative index in lung tumours, defined by Ki67 staining. The distribution of BU31-positive cells is now shown to parallel the distribution of non-dividing cells in a range of normal human and rat tissues, although neuroendocrine cells and germ cells in the testis show no reactivity. Cells grown in culture and induced to undergo growth arrest show a higher level of labelling with BU31 than their proliferating counterparts. Confocal laser scanning microscopy reveals that the BU31 antigen is distributed predominantly along the nuclear lamina, with occasional internal foci. This distribution is very similar to that of the nuclear membrane proteins lamin A and lamin C, suggesting that the BU31 antigen and lamins A and C could be one and the same. Immunoblotting using recombinant lamin proteins confirmed this proposal. Moreover, a monoclonal antibody to the non-proliferation-associated antigen, statin, also recognizes lamins A and C. These data indicate that the demonstration of lamins A and C can be used to provide information on the proliferative activity of normal and neoplastic tissues. These data also suggest a role for nuclear lamins A and C during cellular quiescence, possibly through the reorganization and maintenance of nuclear structure, or more directly through interactions with the retinoblastoma gene product or related proteins.

3T3 Cells↗
PubMed1995

Polycyclic aromatic hydrocarbon exposure in coal liquefaction workers: the value of urinary 1-hydroxypyrene excretion in the development of occupational hygiene control strategies.

Studies in coal liquefaction workers were conducted to examine relationships between work activities, exposure to polycyclic aromatic hydrocarbons (PAHs) and excretion of urinary 1-hydroxypyrene (1-OHP). In a single-week study in operators, the end of work period 1-OHP excretion was an order of magnitude higher than in a shadow control subject, who experienced exposure by inhalation only (shadowed operator = 15.8 mumol mol-1 creatinine; shadow control = 1.07 mumol mol-1 creatinine). Dermal exposure was estimated to account for over 70% of excreted 1-OHP in exposed workers. A second study over 4 consecutive weeks (multi-week study) showed consistency in 1-OHP excretion from week to week both in operators and laboratory technicians, indicating little variation in weekly exposures for these workers. Excretion levels in maintenance workers however, showed some week to week variation, consistent with the variable nature of exposures associated with this type of work. A further study involving an end of work period spot assessment for all personnel showed a clear distinction between exposed workers (operators and maintenance staff) and other workers not thought to be exposed (laboratory technicians and office staff). Findings in the course of these studies indicated that there is no loss of 1-OHP at 4 degrees C, compared with -20 degrees C. On the basis of work to date at the coal liquefaction facility, hygiene control strategies have been proposed involving periodic urinary 1-OHP monitoring.

Coal↗
PubMed1995

Urinary 1-hydroxypyrene: a biomarker for polycyclic aromatic hydrocarbon exposure in coal liquefaction workers.

This study was undertaken to assess the suitability of urinary 1-hydroxypyrene (1-OHPyr) as a biological marker of polycyclic aromatic hydrocarbon (PAH) exposure in coal liquefaction workers. This is believed to be the first evaluation of the method in coal liquefaction workers. Ten workers were selected from a group of 30 workers considered likely to be at risk of contamination from PAHs by virtue of their jobs. Spot urine samples were collected at the start of a work period and at the end of each work shift, with analysis of 1-OHPyr being undertaken by high-performance liquid chromatography linked to a fluorescence detector. Exposure was assessed by the completion of questionnaires. Excretion of 1-OHPyr increased significantly over the working period, and there was a significant increase in 1-OHPyr where start-shift and end-shift samples were taken over one shift. A significant decrease in 1-OHPyr was found during breaks away from work.

Adult↗
PubMed1995

Exposure to polycyclic aromatic hydrocarbons in coal liquefaction workers: impact of a workwear policy on excretion of urinary 1-hydroxypyrene.

OBJECTIVE: This study was undertaken to assess whether contaminated personal clothing worn beneath a coverall (normal workwear) is a source of potentially significant dermal exposure to polycyclic aromatic hydrocarbons (PAHs) in coal liquefaction workers. METHODS: An intervention study was conducted over a two week period involving 10 workers that reflected the range of activities performed at the factory. A cross over design was used to examine the influence of normal workwear (personal clothing worn beneath a coverall) and intervention workwear (new coverall, shirt, trousers, underwear, socks, and boots) upon excretion of urinary 1-hydroxypyrene (1-OHP) and skin pad deposition of pyrene. RESULTS: The impact of intervention was noted in three ways: (1) A notable reduction (55%) in the mass of 1-OHP excreted on the first day of the intervention phase was found. The median reduction in mass excreted (22.7 nmol) was significant from zero at the 5% level; (95% confidence interval (95% CI) 9.5-40.8 nmol). (2) A notable reduction (82%) in skin pad deposition of pyrene on the first day of the intervention phase was found. The median reduction of 13.20 ng.cm-2 was significant from zero at the 5% level; (95% CI 7.3-26.4 ng.cm-2). (3) About a 50% reduction in 1-OHP concentration over the working week occurred during the intervention phase; an increase of 2.07 mumol/mol creatinine was found from the start to the end of the work period during the intervention phase compared with an increase of 4.06 mumol/mol creatinine during the normal phase. This reduction was not significant at the 5% level. CONCLUSION: The results indicate that on the first day of the working week investigated, significant reductions in absorbtion (as measured by excretion of urinary 1-OHP) and deposition of PAHs (as measured by skin pad deposition of pyrene) can be effected by improvements in workwear policy. The impact of the improved workwear regimen was also detected by reduction in spot urinary 1-OHP concentrations, although this effect was less pronounced. One implication of the findings is that exposure to PAHs may arise from workers' own contaminated personal clothing. As a consequence of this study an improved workwear policy has been implemented at the factory.

Adult↗
PubMed1995

The predicted structure of chick lens CP49 and a variant thereof, CP49ins, the first vertebrate cytoplasmic intermediate filament protein with a lamin-like insertion in helix 1B.

The full length cDNA sequence for the lens-specific intermediate filament protein, CP49, from chicken is presented. The sequence contains features typical of the other intermediate filament proteins, including two major alpha-helical regions, helix I and II and appropriate linker regions. CP49 lacks a C-terminal non-alpha-helical domain and is only the second intermediate filament protein to be described missing this feature. Comparison to the bovine CP49 shows significant homology in all domains except the N-terminal non-alpha-helical domain. Besides bovine CP49, the other protein most homologous to chicken CP49 in the database was keratin 18, a type I keratin. A variant of CP49 is also described, called CP49ins. Of the 61 positive clones identified in the library, two encoded CP49ins, one of these being a full-length clone. The sequence differed to CP49 by the insertion of 49 amino acids in helix IB. This is the first chordate cytoplasmic intermediate filament protein sequence to be identified with an archetypal lamin-like insertion in this helical subdomain and represents a key discovery in tracing the evolutionary pathway of intermediate filament protein family.

Amino Acid Sequence↗
PubMed1993

Bovine filensin possesses primary and secondary structure similarity to intermediate filament proteins.

The cDNA coding for calf filensin, a membrane-associated protein of the lens fiber cells, has been cloned and sequenced. The predicted 755-amino acid-long open reading frame shows primary and secondary structure similarity to intermediate filament (IF) proteins. Filensin can be divided into an NH2-terminal domain (head) of 38 amino acids, a middle domain (rod) of 279 amino acids, and a COOH-terminal domain (tail) of 438 amino acids. The head domain contains a di-arginine/aromatic amino acid motif which is also found in the head domains of various intermediate filament proteins and includes a potential protein kinase A phosphorylation site. By multiple alignment to all known IF protein sequences, the filensin rod, which is the shortest among IF proteins, can be subdivided into three subdomains (coils 1a, 1b, and 2). A 29 amino acid truncation in the coil 2 region accounts for the smaller size of this domain. The filensin tail contains 6 1/2 tandem repeats which match analogous motifs of mammalian neurofilament M and H proteins. We suggest that filensin is a novel IF protein which does not conform to any of the previously described classes. Purified filensin fails to form regular filaments in vitro (Merdes, A., M. Brunkener, H. Horstmann, and S. D. Georgatos. 1991. J. Cell Biol. 115:397-410), probably due to the missing segment in the coil 2 region. Participation of filensin in a filamentous network in vivo may be facilitated by an assembly partner.

Amino Acid Sequence↗
PubMed1975

Determinants of survival following cardiac operations in elderly patients.

Ninety-four cardiac operations were performed on 92 patients 65 years of age and over at the Peter Bent Brigham Hospital, Boston, from July 1970 to July 1974. There were 39 aortic valve replacements, 11 mitral valve replacements, 14 double valve operations, 16 coronary revascularizations, five repairs of aortic dissections, and one atrial septal defect closure. The operative mortality was 11 percent in elective cases and 40 percent in the emergency cases, an overall mortality of 17 percent. There were no hospital deaths following elective double valve operations or coronary bypass procedures. Combined hospital and late mortality of ventricular aneurysmectomy approached 100 percent. Myocardial infarction accounted for eight of the 16 hospital deaths. The overall late mortality has been 7.5 percent. Ninety-seven percent of surviving patients are functional class 1 or 2 with a follow-up of 4 to 48 months. These data suggest that any necessary cardiac surgery, excepting ventricular aneurysmectomies, may be performed electively with low risk and a high likelihood of satisfactory rehabilitation in the elderly age group. The major determinants of mortality are the urgency of the intervention and associated coronary artery disease.

Aged↗