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Biomedical subjects

K M Kurian

Publications and source records attributed to K M Kurian.

11 recordsLinked to original sources

Retention of corneal epithelial cells following Goldmann tonometry: implications for CJD risk.

AIMS: To assess the adequacy of current decontamination methods for the Goldmann tonometer in the context of variant Creutzfeldt-Jakob disease (vCJD). METHODS: Reusable Goldmann tonometer prisms were used to perform applanation tonometry on different groups of patients. Following tonometry, retained materials were collected from the tonometer prism head and examined using cytological methods. The used tonometers were subjected to a series of conditions to evaluate their effect on the residual cell numbers found on the tonometer heads. These included wiping alone and wiping or washing followed by disinfection of the tonometer prism. The effect on cell counts of drying the prism overnight was studied, as well as drying overnight and then wiping and disinfecting. All disinfections were performed with sodium hypochlorite (0.05% w/v). RESULTS: The cytology specimens of 69 patients were studied. Patients using eye drops regularly desquamated significantly more corneal epithelial cells with Goldmann tonometry than patients not using regular eye drops. The mean number of cells was 156 (range 0-470) for patients using eye drops and 14 (4-57) for patients not using eye drops (p = 0.004). Wiping or washing the tonometer head reduced the cell number significantly but neither method completely eliminated cells. The two methods were not significantly different (p=0.3). Drying left a large number of cells (23-320 cells). CONCLUSIONS: Retained corneal epithelial cells, following the standard decontamination routine of tonometer prisms, may represent potential prion infectivity. Manual cleaning was the most important step in reducing epithelial cell retention.

Aged↗

The effect of tamoxifen on breast tumour vascularity.

As there is experimental evidence to suggest that tamoxifen may exert an anti-angiogenic effect, the present study was designed to investigate the effect of primary tamoxifen on breast tumour angiogenesis. Fifty seven patients with large operable primary breast cancers were treated with tamoxifen (20 mg daily) for between three and six months prior to definitive surgery. Clinical response to treatment was assessed by serial ultrasound measurements of tumour volume and a responding tumour was defined as one in which there was a greater than 25% reduction in volume at the end of treatment. Patients underwent a wedge biopsy at diagnosis and definitive surgery on completion of tamoxifen, thus providing tumour sections before and after treatment. Microvessel counts (mvc) were performed following staining with the endothelial cell marker, antibody to Factor VIII, and changes in mvc were correlated with response. Forty three of 57 patients had tumours that responded to tamoxifen. There was no difference in pre-treatment mvc between non-responding and responding tumours. Post-treatment mvc was significantly higher in non-responding than responding tumours. There was a significant reduction in mvc in responding tumours following treatment with tamoxifen, and a significant increase in mvc was detected in non-responding tumours. A significant correlation was demonstrated between percentage change in mvc and percentage reduction in tumour volume. This is the first study to demonstrate a reduction in breast cancer angiogenesis in tumours that have responded to primary tamoxifen in the clinical setting.

Antineoplastic Agents, Hormonal↗

A novel cell culture model for studying differentiation and apoptosis in the mouse mammary gland.

BACKGROUND: This paper describes the derivation and characterization of a novel, conditionally immortal mammary epithelial cell line named KIM-2. These cells were derived from mid-pregnant mammary glands of a mouse harbouring one to two copies of a transgene comprised of the ovine beta-lactoglobulin milk protein gene promoter, driving expression of a temperature-sensitive variant of simian virus-40 (SV40) large T antigen (T-Ag). RESULTS: KIM-2 cells have a characteristic luminal epithelial cell morphology and a stable, nontransformed phenotype at the semipermissive temperature of 37 degrees C. In contrast, at the permissive temperature of 33 degrees C the cells have an elongated spindle-like morphology and become transformed after prolonged culture. Differentiation of KIM-2 cells at 37 degrees C, in response to lactogenic hormones, results in the formation of polarized dome-like structures with tight junctions. This is accompanied by expression of the milk protein genes that encode beta-casein and whey acidic protein (WAP), and activation of the prolactin signalling molecule, signal transducer and activator of transcription (STAT)5. Fully differentiated KIM-2 cultures at 37 degrees C become dependent on lactogenic hormones for survival and undergo extensive apoptosis upon hormone withdrawal, as indicated by nuclear morphology and flow cytometric analysis. KIM-2 cells can be genetically modified by stable transfection and clonal lines isolated that retain the characteristics of untransfected cells. CONCLUSION: KIM-2 cells are a valuable addition, therefore, to currently available lines of mammary epithelial cells. Their capacity for extensive differentiation in the absence of exogenously added basement membrane, and ability to undergo apoptosis in response to physiological signals will provide an invaluable model system for the study of signal transduction pathways and transcriptional regulatory mechanisms that control differentiation and involution in the mammary gland.

Animals↗

A polymorphic tetranucleotide repeat in the CYP19 gene and male breast cancer.

The CYP19 gene codes for the aromatase enzyme that is involved in the synthesis of oestrogens. This case-control study examines the relationship between a tetranucleotide repeat sequence in the CYP19 gene and the development of male breast cancer. No significant differences were found between male breast cancer cases and controls.

Aromatase↗

Retroviral vectors.

Traditionally, the retrovirus is regarded as an enemy to be overcome. However, for the past two decades retroviruses have been harnessed as vehicles for transferring genes into eukaryotic cells, a process known as transduction. During this time, the technology has moved from being a scientific laboratory tool to a potential clinical molecular medicine to be used in gene therapy. This review explains the strategy for harnessing the retrovirus life cycle, the scientific research and clinical applications of this methodology, and its limitations, as well as possible future developments.

Gene Transfer Techniques↗

DNA chip technology.

A mini-revolution is sweeping the world of science and medicine. DNA chip or microarray technology will have a more profound impact than other recent major advances, including DNA sequencing and the polymerase chain reaction (PCR). This mini-review explains the technology, its scope, and impact on science and medicine, as well as its cost and possible limitations.

Chromosome Mapping↗

Reproducibility of microvessel counts in breast cancer specimens.

Assessment of tumour vascularity in core biopsy specimens may be a useful predictor of response to primary therapy. This study addresses practical methodological issues regarding accuracy of tumour vascularity assessments in different breast cancer specimens. Issues addressed in the study are variation caused by (i) inherent observer variation in the method, (ii) tumour heterogeneity and (iii) previous surgical manipulation of tumours. Microvessel counts were performed by two observers on separate occasions and by two different observers. Counts were performed on core biopsies and tumour sections taken simultaneously (n = 16) and with an intervening time interval (n = 21). In addition core biopsies were obtained from the same tumour on two separate occasions (n = 10). A highly significant correlation was found in counts performed by the same observers at different times and between two different observers. No significant correlation was found in counts of core biopsies and tumour sections taken either simultaneously or subsequently. No correlation was found between counts of sequential core biopsies. Study findings suggest that, although microvessel counts may be assessed reproducibly by the same and different observers, counts performed in core biopsies do not accurately reflect those of overall tumour, limiting their potential as predictive or prognostic markers.

Adult↗

Crohn's disease presenting as adenocarcinoma of the small bowel.

Crohn's adenocarcinoma of the small bowel is extremely rare. We report a patient with a 10-year history of nonspecific abdominal symptoms who was found on his first presentation to have Crohn's adenocarcinoma of the small bowel. Despite adequate surgical resection, prognosis for this condition is poor with 2-year cancer free survival of around 9%. Crohn's carcinoma should be suspected in patients with long-standing disease and those with and without excluded segments of bowel.

Adenocarcinoma↗