Biomedical subjects
Publications and source records attributed to L Bowles.
Patients and relatives often assume nurses have a higher level of knowledge than they actually possess. In the search for a professional body of knowledge, nurses may underestimate the valuable lessons patients can teach them. The nursing press may exacerbate the theory-practice gap by underrepresenting the experiences of patients, careers and relatives.
The pattern of connexin43 expression in developing chick limb buds was examined using a site-specific polyclonal antibody and confocal microscopy. Connexin43 is expressed at stages of limb development when epithelial-mesenchymal interactions are occurring that mediate morphogenesis. Extensive labeling was observed in the apical ectodermal ridge and labeling was also found in underlying mesenchyme cells at the tip of the bud. In mouse limb buds, the same gap junction protein is expressed only in the apical ridge. Manipulations of developing chick wing buds show that mesenchymal expression of connexin43 appears to be controlled by the apical ectodermal ridge. When the apical ridge is surgically removed and limb truncations result, mesenchymal labeling is markedly reduced and conversely the grafting of an additional ridge induces connexin43 expression between underlying mesenchymal cells which do not normally show expression at this stage of development. In addition, a treatment with retinoic acid that flattens the apical ridge and inhibits bud outgrowth reduces expression in both mesenchymal and epithelial tissues. The abolition of connexin43 expression in mesenchymal and epithelial domains when bud outgrowth is halted suggests that synthesis of this gap junction protein is related to the epithelial-mesenchymal interactions that mediate morphogenesis of the bud.
It has been established that loss of tumour suppressor genes is crucial in carcinogenesis. There has been no reported study on searching for tumour suppressor genes in cholangiocarcinomas as yet. In order to investigate the loss of heterozygosity (LOH), which may represent such gene loss, in cholangiocarcinoma, we studied 14 patients with this tumour using restriction fragment length polymorphism analysis. Twenty-two probes assigned to chromosomes 1, 5, 7, 9, 11, 12, 13, 14, 16, 17 and 18 were used. Allelic losses were found in chromosomal regions 5q35-qter and 17p13. Loss of genetic material in these regions in cholangiocarcinoma was shared with hepatocellular carcinoma. Probes for other chromosomes have as yet shown no consistent LOH. In conclusion, this study for the first time showed LOH on chromosomes 5 and 17 in cholangiocarcinoma.
As yet, there is no reported study of chromosome allele loss in fibrolamellar carcinoma (FLC), a distinct, rare variant of hepatocellular carcinoma (HCC). We searched for evidence of allele loss in FLC using 18 DNA probes for 10 chromosomes and compared the pattern of loss with our series of HCC. Two of the probes, lambda MS32 (1q42-43) and cMS621 (5p) showed allele losses in one tumour, while other probes showed no loss. The frequency of allele loss in FLC was much lower than in HCC, which may be associated with their different prognoses.
Familial adenomatous polyposis, an inherited pre-malignant condition, is caused by mutation in the adenomatous polyposis coli (APC) gene at chromosome 5q22. The lifetime risk of carcinoma approaches 100%, with an average age at death from cancer of 40 years, allowing most patients to complete reproduction. Since there is no evidence for a rising incidence, this is at variance with an apparently high mutation rate. We present evidence for the delineation of a severe form, which hitherto has largely been maintained by fresh mutation. An atypically high frequency of loss of heterozygosity at chromosome 5q22 in small adenomas correlated with an early age of onset or malignancy in two patients, both due to fresh mutation. In both cases, the mutation in APC was shown to be a commonly occurring deletion, leading us to postulate the co-existence of a modifying gene.
We have previously shown that the tumor suppressor gene for hepatocellular carcinoma (HCC) without cirrhosis may be located on chromosome 5q35-qter. In this study, we analyzed nine cases of primary HCC without cirrhosis using probes from the MCC and APC genes, which are in the region 5q21-22. None of the informative cases had allele loss detected by these probes, whereas the probe lambda MS8 for the region 5q35-qter showed allele loss in six out of six informative cases. The results confirm that the putative tumor suppressor gene for HCC without cirrhosis on chromosome 5q is distinct from the MCC and APC genes.
Little is known of the molecular-genetic changes in carcinoma of the pancreas (CaP). In order to investigate the allele loss, or loss of heterozygosity (LOH), in CaP, we studied 13 patients with exocrine CaP and two with endocrine CaP using restriction fragment length polymorphism analysis. Twenty probes assigned to chromosomes 1, 5, 7, 9, 11, 12, 13, 14, 16, 17 and 18 were used. The frequency of LOH, or fractional allele loss (FAL), was found in two endocrine tumours to be 0.333 and 0.455 respectively; and FAL in 13 oxocrine tumours ranged from 0 to 0.25. Allele loss was shown in both exocrine and endocrine tumours by the probes Lambda MS1 at 1p33-35, and pMS51 at 11q13. Probes for other chromosomes have as yet shown no consistent LOH. In conclusion, the study showed LOH on chromosomes 1 and 11 in both exocrine and endocrine CaP.
DNA restriction fragment length polymorphism analysis was carried out on a primary and recurrent hepatocellular carcinoma in a hepatitis B virus negative patient. For the primary tumour, allele losses were found on the short arm of chromosome 17 (probe: p144-D6, 17p13) and the long arm of chromosome 5 with the probe Lambda MS8 (5q35-qter); other probes showed either no allele loss or a non-informative pattern. The recurrent cancer also showed allele loss with p144-D6, but not with Lambda MS8. In addition, the recurrent tumour had allele losses with Lambda MS43 (12q24.3-qter), pYNZ22 (17p13), and DNA rearrangement revealed by the probe Lambda MS32 (1q42-43), a pattern not seen in the primary lesion. These results indicate that the second hepatocellular carcinoma was of independent clonality and probably represents a de novo neoplasm rather than a recurrence.
Suppressor gene loci involved in the development of hepatocellular carcinoma (HCC) have not been fully identified. The aim of this study was to look for consistent allele loss, or loss of heterozygosity (LOH), in HCC which might represent such gene loci. We have prepared DNA from tumour and non-tumour material from 16 patients with HCC (nine with and seven without liver cirrhosis). Tumour DNA was compared with non-tumour DNA by Southern analysis performed with a panel of 22 probes recognising restriction fragment length polymorphisms assigned to chromosomes 1, 4, 5, 7, 9, 11, 12, 13, 14, 16, 17, 18 and 20. Non-tumour DNA from five of the seven patients with HCC without cirrhosis was heterozygous with the probe Lambda MS8 (5q35-qter), and in all five there was LOH in tumour DNA. Probes for other regions of chromosome 5 have as yet shown no LOH in this group of patients. Cirrhotic HCC patients exhibited LOH on chromosomes 1q and 5p but not in the region 5q35-qter. Both groups of HCC showed LOH on chromosome 17p13. Screening with other probes has not shown any consistent LOH in either group as yet. A comparison of LOH on chromosome 5 in seven patients with colorectal metastasis in the liver showed a different pattern, which suggests that the proposed tumour suppressor gene locus for HCC without cirrhosis on chromosome 5 appears to be distinct from the familial adenomatous polyposis coli gene.
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Much has been written on the education of patients about their medication, and yet what patients need to know has not been identified and agreed upon by professionals. This study sought to design a tool for this purpose using a series of interviews with experts to identify categories of information. Many core categories were identified and ambiguous sections such as 'side-effects' were clarified. A test-re-test strategy was used to identify the reliability of the resulting questionnaire. A high level of inconsistencies and a low response rate were, in part, attributable to poor design and distribution of the questionnaire. Other contributory factors and the reluctance/inability of respondents to identify what they felt patients should know about their medication are discussed. Some deficits are identified, in addition to an agreement that current systems for educating patients are inadequate. Areas for future research are also identified.
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