Biomedical subjects
Publications and source records attributed to K Cooper.
We report a unique case of a salivary gland type of "hybrid carcinoma" arising within a Bartholin's gland adenoma. The tumor was characterized by large areas of an epithelial-myoepithelial carcinoma similar to that of the salivary gland with a peripheral infiltrative pattern of an adenoid cystic carcinoma (ACC).
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
It is well recognized that exposure to solar radiation is a major risk factor for the development of skin cancer, photoaged skin, and immune system alterations. However, major questions remain regarding the specific wavelengths and type of exposure that incur risk. The purpose of this article is to critically examine, on the basis of current knowledge, the impact of stratospheric ozone depletions, tanning bed skin cancer risk, the safety of sunscreens as an important element of our solar protection strategies, the wavelengths of solar radiation responsible for melanoma, and the incidence of melanoma. Recommendations are made on prevention strategies and public health messages.
For more than 15 years, the murine local lymph node assay (LLNA) has undergone development, evaluation and validation as an alternative approach to the predictive identification of skin sensitizing chemicals. The criteria by which sensitizing chemicals are distinguished from those without significant skin sensitising hazard were developed empirically and were based on experience rather than a mathematical formula or statistical method. The current practice is to classify, as skin sensitizers, those chemicals which at one or more test concentrations stimulate a threefold or greater increase in the proliferative activity in draining lymph node cells. Despite the apparent confirmation of the utility of this approach from the extensive data available, there has not previously been any attempt to substantiate the accuracy of this criterion. In this present investigations, data from 134 chemicals tested in the LLNA and in the guinea pig and/or for which there exists clear evidence relating to human skin sensitization potential, have been subjected to a rigorous statistical evaluation using Receiver Operating Characteristic (ROC) curves. Whether the analysis is based on a comparison with guinea pig or human data, the results indicate that the empirically derived threefold threshold is an acceptable practical value for hazard identification.
Lead (Pb) is known to negatively affect glutathione (GSH) metabolism in the lens. The present study examined the effects of Captopril, Taurine, and alpha-Lipoic acid on the Pb-induced GSH depletion and lipid peroxide increase in the lenticular system. Captopril administration returned the GSH, cysteine (CYS), and malondialdehyde (MDA) levels to near normal. Following Taurine administration the GSH, CYS and MDA levels were intermediate between the control group and the Pb group levels. Alpha-Lipoic acid administration, however, only increased the CYS levels. No significant changes in oxidized glutathione (GSSG) levels were observed in any treatment group.
Adenoid cystic carcinomas (ACCs) and adenoid basal carcinomas (ABCs) are rare neoplasms of the uterine cervix that are currently regarded as distinct clinicopathologic entities. Accurate distinction between ABCs and ACCs is of clinical importance because of differences in their biological behavior. This study compares the morphologic, mucin, and immunohistochemical profiles of 18 cervical ACCs, 8 ABCs, and 1 combined ABC-ACC. Serial sections from the 27 cases were stained with hematoxylin and eosin, periodic acid-Schiff-diastase, mucicarmine, and alcian blue and subjected to a panel of immunoperoxidase markers, namely, MNF116, CAM 5.2, CK7, CK20, epithelial membrane antigen, carcinoembryonic antigen (CEA), S-100, HHF 35, laminin, and type IV collagen. One ACC was also examined ultrastructurally. Almost all patients were postmenopausal black women. The distinction between ABC and ACC was best made morphologically. Divergent epithelial differentiation was seen in 18 cases (11 ACCs, 6 ABCs, and 1 ABC-ACC). Six cases with intact surface epithelium showed a high grade squamous intraepithelial lesion. There was no significant difference in mucin staining. Both tumor types had a similar immunohistochemical profile, apart from type IV collagen and laminin staining, which occurred exclusively in relation to the extracellular basement membranelike material in the ACC. Eleven ACCs and three ABCs were S-100-positive, including the respective ACC and ABC components of the combined ABC-ACC. Eight of the S-100-positive neoplasms with ACC morphology also stained with HHF 35, suggesting myoepithelial differentiation. The latter was confirmed in one ACC examined ultrastructurally. The similar clinical profiles, apart from the different biological behavior, capacity for divergent differentiation, and the occurrence of ABC areas in some ACCs and vice versa suggest that these tumors may share a common histogenesis, forming part of a morphologic and biologic spectrum of basaloid cervical neoplasms of putative "reserve cell" origin. Circumstantial evidence suggests that ABC may be a precursor of cervical ACC.
AIMS: To determine whether home intervention by a specialist health visitor affects the outcome of children with failure to thrive. METHODS: Children referred for failure to thrive were randomised to receive conventional care, or conventional care and additional specialist home visiting for 12 months. Outcomes measured were growth, diet, use of health care resources, and Bayley, HAD (hospital anxiety and depression), and behavioural scales. RESULTS: Eighty three children, aged 4-30 months, were enrolled, 42 received specialist health visitor intervention. Children in both groups showed good weight gain (mean (SD) increase in weight SD score for the specialist health visitor intervention group 0.59 (0.63) v 0.42 (0.62) for the control group). Children < 12 months in the intervention group showed a higher mean (SD) increase in weight SD score than the control group (0.82 (0.86) v 0.42 (0.79)). Both groups improved in developmental score and energy intake. No significant differences were found for the primary outcome measures, but controls had significantly more dietary referrals, social service involvement, and hospital admissions, and were less compliant with appointments. CONCLUSIONS: The study failed to show that specialist health visitor intervention conferred additional benefits for the child. However, the specialist health visitor did provide a more coordinated approach, with significant savings in terms of health service use. Problems inherent to health service research are discussed.
AIMS: Bacillary angiomatosis is a rare pseudoneoplastic angioproliferative lesion occurring in patients with AIDS. This condition has been associated with Bartonella henselae and Bartonella quintana infections. Human herpesvirus 8 (HHV-8) is thought to be the causative agent of Kaposi's sarcoma, a vasoproliferative neoplasm, also commonly found in patients with AIDS. The presence of HHV-8 in a cohort of patients with bacillary angiomatosis was investigated. METHODS: Eight cutaneous cases of biopsy confirmed bacillary angiomatosis were assessed for HHV-8 using standard solution phase polymerase chain reaction (PCR). RESULTS: No case of bacillary angiomatosis harboured HHV-8 DNA. CONCLUSIONS: HHV-8 was not demonstrated in the lesions of bacillary angiomatosis and therefore does not appear to play a role in the pathogenesis of this pseudoneoplastic angioproliferative disorder. This finding might be useful in the distinction of bacillary angiomatosis from Kaposi's sarcoma, because lesions from patients with Kaposi's sarcoma almost always contains HHV-8 DNA.
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The aim of this study was to identify the role of bcl-2 protein expression in precancerous lesions of the cervix in patients from Johannesburg, South Africa and to correlate this expression with human papillomavirus (HPV) status. Archival cervical biopsy specimens (n = 107) of normal squamous epithelia (n = 18), pure HPV squamous epithelial lesions (n = 15), cervical intraepithelial neoplasia (CIN) I lesions (n = 17), CIN II lesions (n = 26), and CIN III lesions (n = 31) underwent bcl-2 immunohistochemical analysis with use of the streptavidin-biotin complex/horseradish peroxidase system and nonisotopic in situ hybridization for the detection of HPV DNA. Although 45 (61%) of the 74 CIN lesions demonstrated bcl-2 protein expression in the epithelia, most seemed to be in a patchy basal cell distribution, with a 1+ to 2+ intensity. Furthermore, comparison of bcl-2 immunoreaction between the low and high grades of the CIN lesions did not reveal significant differences. In addition, there was no apparent link between the presence of HPV DNA and bcl-2 expression in the CIN lesions. In contrast to previous studies that showed an increase in bcl-2 immunostaining intensity with increasing severity of CIN, only 4 (5.4%) of our 74 CIN specimens satisfied this pattern. Hence, we suggest that bcl-2 protein expression might not play a significant role in the majority of CIN lesions in this population group and that it might not correlate with HPV status.
Lead (Pb) is known to disrupt the pro-oxidant/anti-oxidant balance of tissues which leads to biochemical and physiological dysfunction. The present study investigated the effects of exposure on the redox status of the lenses of Fisher 344 rats and examined whether antioxidant or chelator administration reversed these changes. Animals were given 5 weeks of 2000 ppm Pb exposure followed by 1 week of either antioxidant, chelator or distilled water administration. Glutathione (GSH) and cysteine (CYS) levels decreased in the Pb-exposed group. N-acetylcysteine or 2,3-dimercaptopsuccinic acid (Succimer) supplementation following Pb intoxication resulted in increases in the GSH and CYS levels. Protein bound glutathione (PSSG) and cysteine (PSSC) increased following Pb exposure. In the Succimer-treated animals, the PSSG decreased significantly. The glutathione disulfide (GSSG) levels remained unchanged. Malondialdehyde (MDA) levels, a major lipid peroxidation byproduct, increased following Pb exposure and decreased following Succimer treatment. Our results suggest that antioxidant supplementation, as well as chelation, following Pb exposure may enhance the reductive status of lenses.
The SAR of a series of 2-(7-chromanyl)benzoic acids has been investigated with the aim of identifying potent and selective LTB4 receptor antagonists that maintain potency in complex biological fluids. We found optimal activity in derivatives with electron-withdrawing groups in the benzoic acid ring and with an unsubstituted C-3 benzyl group on the chromanol nucleus. While compounds containing a 3-(4-phenyl)benzyl chromanol substituent were potent LTB4 receptor antagonists, the increased lipophilicity imparted by the additional phenyl substituent led to decreased potency in the presence of plasma proteins. From among the potent compounds identified, CP-195543, the 5'-trifluoromethyl 3-benzyl chromanol, was selected for development.
A testicular mass aspirate was received from a 22-yr-old patient with known non-Hodgkin's lymphoma. The cells were large and pleomorphic, occurring in syncytial fragments and demonstrating abundant cytoplasm. No lymphoglandular bodies were seen. As characteristic lymphoma criteria were not present, a cytodiagnosis of germ-cell tumor was suggested, and testicular biopsy advised. The final histopathology report, however, was of a CD 56-positive (large-cell) T-natural killer cell lymphoma, of which this appears to be the first example described and illustrated cytologically.
AIMS: To describe two cases of spindle epithelial tumour with thymus-like element (SETTLE) which are composed predominantly of spindle cells. In addition, to highlight some unusual histological features in SETTLE and discuss its separation from histological mimics. METHODS AND RESULTS: The thyroid masses were in a 4-year-old boy and a 25-year-old male. Both patients were euthyroid and were well except for thyromegaly. The specimens were formalin fixed, and immunohistochemistry was performed on this material using a panel of antibodies following microwave antigen retrieval. Morphologically, the dominant pattern was of sheets of spindle cells arranged in several patterns. There was mild pleomorphism and occasional mitoses. There were very small foci of squamous epithelium and occasional ductular structures. The stroma was composed of fibrous tissue and isolated areas of calcification were noted. The spindle cells showed strong and diffuse immunoreactivity with AE1/3, CAM5.2 and vimentin. CONCLUSION: We describe two cases of SETTLE that are composed mainly of spindle cells and only a very focal ductular component. In addition, calcification was noted within the stroma in one of the cases. These predominantly spindle examples of SETTLE must be separated from synovial sarcoma, which is a more mitotically active, aggressive tumour displaying only patchy immunopositivity with epithelial markers.