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Biomedical subjects

A J Robertson

Publications and source records attributed to A J Robertson.

At least 19 recordsLinked to original sources

Protein tyrosine and serine-threonine phosphatases in the sea urchin, Strongylocentrotus purpuratus: identification and potential functions.

Protein phosphatases, in coordination with protein kinases, play crucial roles in regulation of signaling pathways. To identify protein tyrosine phosphatases (PTPs) and serine-threonine (ser-thr) phosphatases in the Strongylocentrotus purpuratus genome, 179 annotated sequences were studied (122 PTPs, 57 ser-thr phosphatases). Sequence analysis identified 91 phosphatases (33 conventional PTPs, 31 dual specificity phosphatases, 1 Class III Cysteine-based PTP, 1 Asp-based PTP, and 25 ser-thr phosphatases). Using catalytic sites, levels of conservation and constraint in amino acid sequence were examined. Nine of 25 receptor PTPs (RPTPs) corresponded to human, nematode, or fly homologues. Domain structure revealed that sea urchin-specific RPTPs including two, PTPRLec and PTPRscav, may act in immune defense. Embryonic transcription of each phosphatase was recorded from a high-density oligonucleotide tiling microarray experiment. Most RPTPs are expressed at very low levels, whereas nonreceptor PTPs (NRPTPs) are generally expressed at moderate levels. High expression was detected in MAP kinase phosphatases (MKPs) and numerous ser-thr phosphatases. For several expressed NRPTPs, MKPs, and ser-thr phosphatases, morpholino antisense-mediated knockdowns were performed and phenotypes obtained. Finally, to assess roles of annotated phosphatases in endomesoderm formation, a literature review of phosphatase functions in model organisms was superimposed on sea urchin developmental pathways to predict areas of functional activity.

Animals↗

Impact of a national external quality assessment scheme for breast pathology in the UK.

BACKGROUND: This article presents the results and observed effects of the UK National Health Service Breast Screening Programme (NHSBSP) external quality assurance scheme in breast histopathology. AIMS/METHODS: The major objectives were to monitor and improve the consistency of diagnoses made by pathologists and the quality of prognostic information in pathology reports. The scheme is based on a twice yearly circulation of 12 cases to over 600 registered participants. The level of agreement was generally measured using kappa statistics. RESULTS: Four main situations were encountered with respect to diagnostic consistency, namely: (1) where consistency is naturally very high-this included diagnosing in situ and invasive carcinomas (and certain distinctive subtypes) and uncomplicated benign lesions; (2) where the level of consistency was low but could be improved by making guidelines more detailed and explicit-this included histological grading; (3) where consistency could be improved but only by changing the system of classification-this included classification of ductal carcinoma in situ; and (4) where no improvement in consistency could be achieved-this included diagnosing atypical hyperplasia and reporting vascular invasion. Size measurements were more consistent for invasive than in situ carcinomas. Even in cases where there is a high level of agreement on tumour size, a few widely outlying measurements were encountered, for which no explanation is readily forthcoming. CONCLUSIONS: These results broadly confirm the robustness of the systems of breast disease diagnosis and classification adopted by the NHSBSP, and also identify areas where improvement or new approaches are required.

Breast Neoplasms↗

The NHS breast screening programme (pathology) EQA: experience in recent years relating to issues involved in individual performance appraisal.

BACKGROUND: The original role of the National Health Service breast screening programme (pathology) external quality assessment (EQA) scheme was educational; it aimed to raise standards, reinforce use of common terminology, and assess the consistency of pathology reporting of breast disease in the UK. AIMS/METHODS: To examine the performance (scores) of pathologists participating in the scheme in recent years. The scheme has evolved to help identify poor performers, reliant upon setting an acceptable cutpoint. Therefore, the effects of different cutpoint strategies were evaluated and implications discussed. RESULTS/CONCLUSIONS: Pathologists who joined the scheme improved over time, particularly those who did less well initially. There was no obvious association between performance and the number of breast cancer cases reported each year. This is not unexpected because the EQA does not measure expertise, but was established to demonstrate a common level of performance (conformity to consensus) for routine cases, rather than the ability to diagnose unusual/difficult cases. A new method of establishing cutpoints using interquartile ranges is proposed. The findings also suggest that EQA can alter a pathologist's practice: those who leave the scheme (for whatever reason) have, on average, marginally lower scores. Consequently, with the cutpoint methodology currently used (which is common to several EQA schemes) there is the potential for the cutpoint to drift upwards. In future, individuals previously deemed competent could subsequently be erroneously labelled as poor performers. Due consideration should be given to this issue with future development of schemes.

Breast Neoplasms↗

Observer variability in the Goseki grouping of gastric adenocarcinoma in resection and biopsy specimens.

AIMS: The Goseki grouping of gastric adenocarcinoma has been suggested as a possible prognostic factor. In those centres where it is used, it may be valuable to assess the Goseki grouping of a tumour on the initial diagnostic biopsy as well as on the resection specimen since it may in theory influence management. We examined the robustness of Goseki grouping of gastric adenocarcinoma in representative sections from resection and biopsy specimens in order to assess the consistency of agreement among a group of pathologists. METHODS: A single representative block from 100 gastric resection specimens was studied using a haematoxylin and eosin and mucin (alcian blue/periodic acid-Schiff) stain. These were circulated in batches to members of a group of 12 pathologists who each completed a simple proforma confirming the presence of carcinoma and assigning a Goseki group. In a second circulation the diagnostic biopsy specimen taken prior to resection was examined in the same way. This allowed comparison of the Goseki group of the biopsy and resection specimens. RESULTS: In both studies kappa statistics showed good agreement on tubular differentiation of the carcinoma, but only moderate agreement for the intracellular mucin production, resulting in moderate agreement for the final Goseki group. Correlation between the Goseki group assigned on the biopsy and resected specimens was seen in 62% of the cases. However, the reproducibility was low (kappa 0.375). CONCLUSIONS: The Goseki grouping of resected gastric adenocarcinoma is reproducible and can be used in prognostication. Goseki grouping of biopsy specimens is of limited value in predicting the Goseki group assigned to the resected carcinoma.

Adenocarcinoma↗

Paediatric dentistry in the new millennium: 4. Cost-effective restorative techniques for primary molars.

In the fourth article in this series the techniques for carrying out pulp therapy and stainless steel restoration in primary molars are discussed. Early pulp involvement in primary molars means that pulp therapy and the use of appropriate coronal restoration, such as stainless steel crowns, are indispensable if repetitive restoration of primary molars is to be avoided. These techniques themselves are not difficult to carry out once the child's co-operation is established and should be well within the capability of any dentist with an interest in the dental care of children.

Cementation↗

Chromosomal radiosensitivity in G2-phase lymphocytes identifies breast cancer patients with distinctive tumour characteristics.

A substantial proportion of women with breast cancer exhibit an abnormally high radiosensitivity as measured by the frequency of chromatid breaks induced in G2-phase, PHA stimulated lymphocytes. Chromatid break frequencies were compared for a cohort of previously untreated sporadic breast cancer patients and hospital outpatient controls. In the breast cancer group 46% showed high radiosensitivity compared to 14% of controls (P< 0.001). Comparison of those breast cancer patients with a high G2 radiosensitivity (G2RS) versus those with a low G2RS showed no difference in menopausal status or age but the high G2RS group had on average a lower score on the Nottingham Prognostic Index. Predicted survival in the high G2RS group at 15 years was 55% compared to 36% for the low G2RS group. Furthermore, 81% of tumours from the high G2RS were oestrogen receptor positive compared to 45% from the low G2RS group. Thus high G2RS identifies a sub-population of patients with distinctive tumour characteristics and with a predicted improved prognosis as compared with those in the low G2RS group. Our findings imply that besides influencing risk of breast cancer the genetic factors determining G2 radiosensitivity also influence the tumour characteristics and prognosis in these patients.

Adult↗

Consistency of histopathological reporting of laryngeal dysplasia. The Scottish Pathology Consistency Group.

AIMS: Clinical management of premalignant and malignant lesions of the larynx is dependent on histopathological evaluation. The Scottish Pathology Consistency Group assessed interobserver variation in the evaluation of laryngeal dysplasia. METHODS AND RESULTS: One hundred laryngeal biopsies ranging from normal to invasive carcinoma were assessed. The overall Kappa result of 0.32 was disappointing. However, agreement on those categories which dictate significantly different management was more favourable. The Kappa figure for mild dysplasia versus severe dysplasia/CIS was 0.7, the Kappa figure for mild dysplasia versus severe dysplasia/CIS and invasive carcinoma was 0.77. The Kappa figure for mild and moderate dysplasia versus severe dysplasia/ CIS and invasive carcinoma was 0.57. An attempt to use a two grade system gave a Kappa figure of 0.52. CONCLUSIONS: Our group had a satisfactory agreement on the distinction of mild from severe dysplasia and on microinvasive carcinoma without any discussion as to histopathological criteria to be used. Clinical management--review endoscopy, repeat cord stripping, radiotherapy and laryngectomy--is in general dependent on histological assessment. Thus the agreement on categories which underpin clinical management is reassuring. However, assessment of moderate dysplasia remains problematic. An attempt to utilize a two grade system--low grade from high grade dysplasia/CIS--may have merit. The implications of the terminology used must be agreed among pathologists and clinicians working closely within clinicopathological cancer groups.

Adenocarcinoma↗

Low dose aspirin as prophylaxis against renal-vein thrombosis in renal-transplant recipients.

BACKGROUND: Renal-vein thrombosis (RVT) is an infrequent event that accounts for a high proportion of early renal allograft losses, since graft failure secondary to acute irreversible rejection is now relatively rare. The cause of RVT may be related to technical problems, clotting disorders, diabetes, or cyclosporin, but is often difficult to define. METHODS: This retrospective study was performed to examine the influence of aspirin on the incidence of RVT in cadaveric and living-related renal transplant recipients receiving cyclosporin-based triple immunosuppression. The Oxford Transplant Centre database was used to identify all early (<30 day) non-immunological graft failures and case histories were examined for clinical and pathological evidence of RVT. In July 1991, aspirin (75 mg o.d. starting immediately before and continuing for 1 month post-transplant) was introduced as routine prophylaxis against RVT. Prior to this, aspirin prophylaxis was not used. RESULTS: In the 6-year period from July 1985 to June 1991, there were 27 cases of RVT in 475 transplants (5.6%). In the subsequent 6-year period, there were six cases of RVT in 480 transplants (1.2%) (P:<0.01). CONCLUSION: Although not abolished, this indicates a significant reduction in the incidence of RVT with the addition of low-dose aspirin.

Adult↗

Splenic artery aneurysm and orthotopic liver transplantation.

Splenic artery aneurysms are a rare but potentially fatal complication after liver transplantation. We report three cases presenting in a 12-month period in adult patients who underwent transplantation for chronic liver disease. Doppler ultrasound of the splenic artery should be performed in all patients with cirrhosis and portal hypertension who are being assessed for liver transplantation. The aneurysm can be ligated at the time of transplantation.

Adult↗

The study of the process of fluid-phase endocytosis in cervical squamous cells using fluorescent microspheres.

Physiological processes in cervical squamous epithelium have not been extensively studied. Perhaps understandably, most of the research has concentrated on the pathology of the cervix, in particular dysplasia and malignancy. Fluid-phase endocytosis is a physiological process which has been demonstrated to be important in understanding disease development at other squamous epithelial sites, e.g. oesophagus. In this study, we have demonstrated by a new methodology developed in our laboratory using fluorescent microspheres and flow cytometry that fluid-phase endocytosis occurs in cervical squamous cells. The process has been shown to be dose- and time-dependent. This novel approach provides a means to improve our understanding of the physiological functions of the cervix and may provide insight into the pathogenesis of cervical neoplastic and non-neoplastic disease.

Cervix Uteri↗

Cross-polarized photography in the study of enamel defects in dental paediatrics.

An investigative trial was set up to determine the efficacy and practicality of using cross-polarized photography in the assessment of enamel defects. Twenty patients were photographed using this technique. The photography was assessed by ten clinicians, each of whom completed a questionnaire. Two calibrated examiners using the DDE Epidemiology and Screening Indices also undertook assessment. The results show overwhelming evidence to support the use of cross-polarization, with significant increase in agreement between the assessors, than that which could be obtained by conventional photography. It also enhanced the visual detail of enamel defects enabling changes in the appearance to be assessed by the DDE Indices.

Child↗

Isolation, chromosomal localization, and differential expression of mitochondrial manganese superoxide dismutase and chloroplastic copper/zinc superoxide dismutase genes in wheat.

Superoxide dismutase (SOD) gene expression was investigated to elucidate its role in drought and freezing tolerance in spring and winter wheat (Triticum aestivum). cDNAs encoding chloroplastic Cu/ZnSODs and mitochondrial MnSODs were isolated from wheat. MnSOD and Cu/ZnSOD genes were mapped to the long arms of the homologous group-2 and -7 chromosomes, respectively. Northern blots indicated that MnSOD genes were drought inducible and decreased after rehydration. In contrast, Cu/ZnSOD mRNA was not drought inducible but increased after rehydration. In both spring and winter wheat seedlings exposed to 2 degrees C, MnSOD transcripts attained maximum levels between 7 and 49 d. Transcripts of Cu/ZnSOD mRNA were detected sooner in winter than in spring wheat; however, they disappeared after 21 d of acclimation. Transcripts of both classes of SOD genes increased during natural acclimation in both spring and winter types. Exposure of fully hardened plants to three nonlethal freeze-thaw cycles resulted in Cu/Zn mRNA accumulation; however, MnSOD mRNA levels declined in spring wheat but remained unchanged in winter wheat. The results of the dehydration and freeze-thaw-cycle experiments suggest that winter wheat has evolved a more effective stress-repair mechanism than spring wheat.

Chloroplasts↗

Laparoscopic cholecystectomy injury: an unusual indication for liver transplantation.

The introduction of laparoscopic cholecystectomy has been associated with a rise in the number of reported bile duct injuries (0.3%-0.8%). Significant vascular injuries are rare (0.16%), but may lead to life-threatening complications. We present a case report of a patient undergoing transplantation for a laparoscopic cholecystectomy injury.

Adult↗

Epithelial atypia and squamous metaplasia in nasal polyps.

Fifteen routine nasal polypectomy specimens submitted to our laboratory over an eight-month period were noted to show marked atypia within areas of squamous metaplasia to a degree suggestive of dysplasia. Reviewing the literature revealed little published work in this area, especially recently. Further nasal polyp cases from this, and a similar previous time period, were re-examined, and possible causes for these changes discussed.

Adult↗

Observer variability in the histopathological reporting of needle biopsy specimens of the prostate.

The Scottish Pathology Consistency Group has in previous studies examined the consistency of histopathological reporting of biopsies from the cervix, bladder, bronchus, and rectum. In the current study, consisting of 100 needle biopsy specimens of the prostate, a single hematoxylin-eosin (H&E) slide from each case was circulated in batches of 10 to the 12 pathologists, who filled in a simple proforma. This had two sections: a diagnostic category (benign; suspicious or malignant) along with a standard Gleason score for those regarded as malignant. The majority diagnosis of the 100 cases was benign, 53; suspicious, 1; and malignant, 46. The Kappa value for benign cases versus others was 0.86 and for malignant cases versus others was 0.91. Analysis of the data on Gleason scores showed a value of 0.54 when cases were divided into two categories (2 to 6 v 7 to 10) and 0.41 when three categories were used (2 to 4; 5 to 6; 7 to 10). Although not initially part of the design of the study, the majority diagnosis was compared with the original reported diagnosis. In a small subset, examination of further levels, basal cell antibody staining, along with further clinical information, was obtained. With this added information, it appears that there were probably 52 benign and 48 malignant cases. Of the 48 malignant cases, the group majority diagnosis was malignant, 46; suspicious, 1; and benign, 1. The original reported diagnosis was 56 benign, 1 suspicious, and 43 malignant. The group therefore appeared to perform better than the original reporting pathologists. When compared with the results of our previous studies, this study has shown that the diagnosis of carcinoma of the prostate on a needle biopsy is robust.

Biopsy, Needle↗

A cell cycle-regulated histone H3 gene of alfalfa with an atypical promoter structure.

The control of cell cycle expression of histone genes in plants is incompletely understood. A new histone H3 gene was cloned from alfalfa (Medicago sativa) that codes for the replication-dependent histone H3.1 variant protein. Despite lacking all promoter sequence motifs that have been associated with cell cycle-dependent histone gene expression in plants, northern analysis of synchronized cells clearly linked gene expression to DNA replication. TTAATNA was recognized as a new sequence element in the 3' untranslated regions of this and all other cell cycle-dependent histone H3 genes of dicotyledonous plants. It is not found in the replication-independent histone H3 genes.

Amino Acid Sequence↗