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M A Parsons

Publications and source records attributed to M A Parsons.

At least 37 records · Page 2Linked to original sources
PubMed2001

Expression of integrins, degradative enzymes and their inhibitors in uveal melanoma: differences between in vitro and in vivo expression.

Posterior uveal melanoma is the most common intraocular malignancy in adults. Metastasis occurs in approximately 40% of all cases and spread is primarily to the liver. Once secondary hepatic disease has developed the prognosis is poor. Metastasis involves a series of adhesion and de-adhesion events, coupled with regulated tissue degradation to facilitate tumour cell invasion and spread to both local and distant sites. These processes are assisted by the expression of integrins and degradative enzymes by both tumour and host cells. Using a series of 10 uveal melanomas, we investigated the expression of a panel of integrins, degradative enzymes and their inhibitors that have been shown to be associated with metastasis. In addition, we undertook to establish if there might be differential expression in response to growth under artificial conditions. All the tumours expressed matrix metalloproteinases (MMP)-2 and-9, tissue inhibitor of metalloproteases (TIMP)-2, urokinase plasminogen activator (u-PA), plasminogen activator inhibitor (PAI)-1 and PAI-2. Differences in the expression of the integrins alpha1beta1, alpha2beta1 and alpha6beta1 were observed; in particular, these differences appeared to relate to expression as a consequence of growth in culture. In summary, uveal melanoma cells express both degradative enzymes and their respective inhibitors, which are important in metastasis. It would appear that differential expression of integrins is present, probably as a response to in vitro stimulation.

Adult↗
PubMed2001

Reduced expression of TAP-1 and TAP-2 in posterior uveal melanoma is associated with progression to metastatic disease.

In order to determine the effects of the loss or reduced expression of molecules associated with antigen presentation (transporter associated with antigen presentation [TAP]-1, TAP-2, low molecular weight protein [LMP]-2 and LMP-7), we examined the expression of these molecules in primary uveal melanoma lesions. Paraffin-embedded sections from 29 primary uveal melanoma lesions were analysed for expression of TAP-1, TAP-2, LMP-2 and LMP-7 using specific primary antibodies followed by a three-stage immunoperoxidase technique. Microscopic examination was undertaken to determine differences in expression of these molecules on the tumour and the surrounding stroma. Overall, 72% (21 out of 29) of the tumours showed some loss or reduced expression of TAP-1, TAP-2, LMP-2 and/or LMP-7. Statistical analysis of these results showed that progression to metastatic disease was strongly associated with reduced expression of TAP-1 (P < 0.05) and TAP-2 (P < 0.01), taking patient age, tumour site and histology into account. We conclude that the reduced expression of molecules important in eliciting an immune response, such as TAP-1 and TAP-2, may facilitate the metastatic spread of uveal melanoma lesions and may have important implications for prospective immunotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Prediction of prognosis in patients with uveal melanoma using fluorescence in situ hybridisation.

BACKGROUND/AIMS: Uveal melanoma is the commonest malignancy of the eye, with a high proportion of patients dying of metastatic disease. Tumours showing a loss of chromosome 3 and gains of chromosome 8 are associated with a worse prognosis. The efficiency of fluorescence in situ hybridisation (FISH) in determining copy numbers of these chromosomes was assessed in individual tumours and related to patient survival. METHODS: 33 fresh frozen samples were analysed with centromeric probes for chromosomes 3 and 8. Patient outcomes were divided into two groups: (1) absence of genetic abnormalities (no genetic imbalance) and (2) presence of genetic abnormalities (genetic imbalance). The log rank test was used to compare survival, which was represented by Kaplan-Meier survival curves. RESULTS: Of the 33 tumours analysed, 16 showed evidence of genetic imbalances. Of these 16 tumours, 14 patients had died by the end of the study, with 10 having died of liver metastases. Of the tumours without evidence of genetic imbalances, five patients had died by the end of the study, although none had died as a result of either liver metastases or from the primary uveal melanoma. The difference in survival between the two groups was highly significant (p<0.0001). CONCLUSION: The authors have shown that FISH analysis for chromosome 3 and 8 is a reliable and efficient technique in the analysis of fresh frozen tumour specimens and is valuable in the prediction of prognosis in individuals with uveal melanomas.

Adult↗
PubMed2001

ACP Best Practice No 164: Necropsy techniques in ophthalmic pathology.

Much important information can be obtained at necropsy by the pathological examination of the eye and its adnexal structures in adults and children. This information may be related to the cause of death (for example, violent shaking trauma in physical child abuse), or may pertain to disease processes affecting the eye, the orbit, and surrounding structures outside the orbit. This article reviews the technical methods used to remove the following: the vitreous (for example, for biochemistry); the eye itself (anterior approach); the eye and orbital contents (posterior approach); the eye, orbit and orbital walls; and the eye, orbital walls, and surrounding structures. The removal of the eye and adnexal ocular structures must be recognised as a "culturally sensitive" issue, which must be approached cautiously. It should only be undertaken for sound scientific reasons, with the fully informed consent of the relatives and/or the coroner (or equivalent authority), and with properly agreed procedures for the eventual retention or disposal of the ocular tissues. For this reason, this article reviews not only the scientific indications and methods for the removal of such tissues, but also the legal and ethical issues that must underpin this pathology "best practice".

Autopsy↗
PubMed2000

Association of specific chromosome alterations with tumour phenotype in posterior uveal melanoma.

Posterior uveal melanomas have recurrent alterations of chromosomes 1, 3, 6 and 8. In particular, changes of chromosomes 3 and 8 occur in association, appear to characterize those tumours with a ciliary body component, and have been shown to be of prognostic significance. The relevance of other chromosome alterations is less certain. We have performed cytogenetic analysis on 42 previously untreated primary posterior uveal melanomas. Of interest was the observation that as tumour size increased the involvement of specific chromosome changes, and the amount of chromosome abnormalities likewise increased. Loss, or partial deletions, of the short arm of chromosome 1 were found to associate with larger ciliary body melanomas; typically, loss of the short arm resulted from unbalanced translocations, the partners of which varied. Trisomy of chromosome 21 occurred more often in ciliary body melanomas, whilst rearrangements of chromosomes 6 and 11 were primarily related to choroidal melanomas. Our results imply that alterations of chromosome 1 are important in the progression of some uveal melanomas, and that other chromosome abnormalities, besides those of chromosomes 3 and 8, are associated with ocular tumours of particular locations.

Adult↗
PubMed1999

Dimorphic immunohistochemical staining in ocular sebaceous neoplasms: a useful diagnostic aid.

PURPOSE: We studied whether patterns of immunostaining in formalin-fixed, paraffin-embedded tissue could help to distinguish between sebaceous neoplasms of the eyelid and other eyelid neoplasms. METHODS: We applied antibodies to human milk fat globule-1 (HMFG1), cytokeratins (PKK1 and MNF116), epithelial membrane antigen (EMA) and carcino-embryonic antigen (CEA) to normal eyelid tissue and to a range of sebaceous lesions of the eyelid; these included sebaceous hyperplasia, sebaceous adenoma and sebaceous epithelioma, in addition to well to poorly differentiated sebaceous carcinoma. RESULTS: The central and peripheral cellular components of normal sebaceous glands and neoplastic sebaceous lesions showed a distinctive dimorphic staining pattern with the antibody panel used. The central foamy 'sebaceous' cells expressed HMFG1 and EMA, but not PKK1 or MNF116, whereas the smaller, peripheral basal and ductal cells expressed PKK1 or MNF116 but not HMFG1 or EMA. CEA expression in sebaceous cells was unhelpful diagnostically. CONCLUSION: Normal sebaceous glands and all sebaceous neoplasms show a dimorphic cell population that can be identified using a small panel of antibodies on formalin-fixed, paraffin-embedded tissue. This distinctive staining pattern can be assessed retrospectively, even in small biopsies, and largely removes the need for fat stains on frozen sections to differentiate sebaceous lesions from other ocular neoplasms. The results also support the suggestion that ocular sebaceous neoplasms arise from a common stem cell, rather than from either sebaceous or basal/ductal cells.

Adenocarcinoma, Sebaceous↗
PubMed1999

Tracking of avoidance of alcohol use and smoking behavior in a fifth grade cohort over three years.

This study examined the maintenance of positive health behavior (avoidance of alcohol use and cigarette smoking) and factors associated with the maintenance of these behaviors from fifth through seventh grade by a cohort of rural students (N = 232). African American and White students showed similar patterns of high avoidance of alcohol until seventh grade. Although more girls avoided use than boys, avoidance decreased in both groups with progression in grade. Mothers', fathers', and best friends' drinking behaviors influenced avoidance behavior; drinking was less likely to occur among those whose parents and friends did not drink. Friends' drinking behavior influenced alcohol use as early as fifth grade. Smoking avoidance was maintained by 74% of the students over the 3 years. Although there were no racial differences in smoking, African Americans started smoking about 1 year earlier than Whites. During seventh grade, an increase in smoking occurred among boys and girls, but was particularly striking among girls. Avoidance of smoking was influenced by mothers' behavior but not fathers'. Best friends' smoking behavior exerted a major influence on avoidance between grades 6 and 7. In grades 5 and 6, those who avoided smoking were more physically active than smokers, but by seventh grade their physical activity declined to a similar level as smokers. Rural adolescent boys seemed to be at early risk for alcohol use and smoking, while rural girls delayed involvement by 1 to 2 years. Communities, schools, and families can help adolescents avoid alcohol use and smoking through early prevention efforts.

Black or African American↗
PubMed1999

Coinfection with influenza B virus does not affect association of Neisseria meningitidis with human nasopharyngeal mucosa in organ culture.

There is an epidemiological association between influenza virus infection and meningococcal disease. Proposed mechanisms are the destruction of the normal epithelial barrier function of the upper respiratory tract by influenza virus or the expression of human or viral surface-exposed proteins that enhance bacterial adherence and/or invasion. To test these hypotheses, human nasopharyngeal mucosa specimens from a total of 19 individual donors were successfully infected with influenza B virus and then inoculated with serogroup B Neisseria meningitidis. Subsequent bacterial association with the epithelial surface was measured in three separate series of experiments by using transmission electron microscopy (n = 6), scanning electron microscopy (n = 6), and counting of viable bacteria within homogenates of explants (n = 7). Penetration of the mucosa was estimated by measuring the count of viable bacteria recovered from explants after exposure to sodium taurocholate. Bacterial association with the surface of explants was time dependent over 24 h of superinfection. Influenza virus did not positively or negatively influence bacterial attachment to or penetration of explant mucosa compared to those of uninfected controls, even when the period of preincubation with virus was extended to 7 days. When proteins were purified from mucosal epithelium and immobilized on nitrocellulose membranes, N. meningitidis attached predominantly to bands corresponding to proteins of 210 and 130 kDa. In the presence of influenza virus infection, these proteins were gradually lost over the course of 72 h. In conclusion, influenza B virus did not increase association of serogroup B N. meningitidis with human nasopharyngeal mucosa.

Antigens, Viral↗
PubMed1998

Transcriptional properties of RNA polymerase II within triplet repeat-containing DNA from the human myotonic dystrophy and fragile X loci.

Expansion of a (CTG)n segment within the 3'-untranslated region of the myotonic dystrophy protein kinase gene alters mRNA production. The inherent ability of RNA polymerase II to transcribe (CTG)17-255 tracts corresponding to DNA from normal, unstable, and affected individuals, and the normal (CGG)54 fragile X repeat tract, was analyzed using a synchronized in vitro transcription system. Core RNA polymerase II transcribed all repeat units irrespective of repeat length or orientation. However, approximately 50% of polymerases transiently halted transcription (with a half-life of approximately 10 +/- 1 s) within the first and second CTG repeat unit and a more transient barrier to elongation was observed roughly centered within repeats 6-9. Transcription within the remainder of the CTG tracts and within the CCG, CGG, and CAG tracts appeared uniform with average transcription rates of 170, 250, 300, and 410 nucleotides/min, respectively. These differences correlated with changes in the sequence-specific transient pausing pattern within the CNG repeat tracts; individual incorporation rates were slower after incorporation of pyrimidine residues. Unexpectedly, approximately 4% of the run-off transcripts were, depending on the repeat sequence, either 15 or 18 nucleotides longer than expected. However, these products were not produced by transcriptional slippage within the repeat tract.

Base Sequence↗
PubMed1998

Template end-to-end transposition by RNA polymerase II.

On 5'-template strand protruding templates, promoter-initiated run-off transcription by RNA polymerase II generates discrete, 15-16-nucleotide (nt) longer than expected products whose production is abrogated by elongation factor SII (Parsons, M. A., Sinden, R. R., and Izban, M. G. (1998) J. Biol. Chem. 273, 26998-27008). We demonstrate that template terminal complexes produce these RNAs and that transcript extension is a general and salt-sensitive (250 mM) feature of run-off transcription. On 5'-overhung templates the extended run-off transcripts appear to be retained within an RNA-DNA-enzyme ternary complex, and SII facilitates resumption of transcript elongation via a dinucleotide truncation intermediate. Moreover, on one of the 5-overhung templates, the initially extended complexes spontaneously resumed transcript extension and were uniquely resistant to salt (250 mM) challenge. However, SII did not facilitate this long distance extension on all template ends. Run-off transcripts on a blunt-ended template were initially extended by 2-11 nt (roughly in 2-nt increments); SII addition either before or after extension resulted in the accumulation of a 4-5-nt extension product. Based on these findings, we propose that the initial and continuously extended RNAs reflect intermediates and successful completion of template end-to-end transposition (template switching) by RNA polymerase II, respectively. Both the template end sequence and structure influenced the success of such an event.

DNA↗
PubMed1998

Health risk behaviors of rural sixth graders.

The purposes of this study were to examine the frequency and risk factors (correlates) of single and concurrent health risk behaviors (HRBs) including obesity, physical inactivity, smoking, and alcohol use in a sample of 352 rural, predominately African-American sixth graders. This study was guided by Jessor's (1992) adolescent risk behavior conceptual framework. Data were collected using physical measures and a self-report questionnaire. Thirty-two percent of the sample had no HRB, 44% had one HRB, and 24% had two or more HRBs. Obesity and physical inactivity were more prevalent in this sample than in the general population. Gender differences in risk factors were evident. Our findings suggest the testing of interventions that focus on the social needs of girls and that influence behavioral modeling for boys to reduce single and concurrent health risk behaviors.

Adolescent↗
PubMed1998

Cytogenetics of iris melanomas: disparity with other uveal tract melanomas.

The chromosomal alterations of iris melanomas are poorly characterized, only one report has been detailed. Cytogenetic analysis was performed on the tumors and heparinized blood samples of three patients with iris melanomas; in one case a primary tumor and its related seedling were examined. On analysis of lymphocytes, two of the patients were found to experience a low level fragility of chromosome 9, in the region of a cutaneous melanoma susceptibility gene. All iris melanoma lesions were karyotyped. Clonal abnormalities of chromosomes 3, 5, 6, 7, 8, 9, 12, 15, 17, 18, 19, and Y were found, and in one case a large number of marker chromosomes were observed. No specific chromosomal change was common to the iris melanomas, but two cases had different abnormalities of chromosomes 5 and 18. Variations between the primary tumor and its related seedling were the acquisition of an additional chromosome 15, and a polyploid form of the cell line in the seedling. This study suggests that the most common chromosomal changes of posterior uveal melanomas are less frequent in iris melanomas. Iris melanomas also appear to experience relatively high levels of chromosomal alterations, including the formation of marker chromosomes, which is perhaps reminiscent of cutaneous melanoma.

Chromosome Aberrations↗
PubMed1998

Simultaneous cell cycle and phenotypic analysis of primary uveal melanoma by flow cytometry.

BACKGROUND AND PURPOSE: DNA ploidy and cell cycle measurements of uveal melanoma tissue are regarded as having limited prognostic significance. In contrast, dual-parameter (DNA monoclonal antibody) flow cytometry offers a convenient and rapid way to screen tumour samples for a variety of phenotypic markers, whilst simultaneously measuring DNA ploidy and cell cycle, and therefore has the increased potential to identify clinically relevant indicators of disease progression. The aim of the present study was to identify a simple yet robust method for isolating, preserving and staining cells that could be analysed by flow cytometry. METHODS: Using a simple preparation procedure, a panel of membrane-associated antibodies (ICAM-1, W632, HLA-DR) and nuclear or cytoplasmic oncoprotein antibodies (c-erbB-2, c-myc, bcl-2, p53), together with positive (PHM-5) and negative (FITC F(ab')2) controls, were assayed. It was considered important to test the protocol with markers expressed on the cell surface, and in the cytoplasm and nucleus, so as not to be restrictive and thereby exclude an antigen of potential clinical interest. In addition, such panels would also enable the generation of a 'phenotypic profile' for each specimen that may reveal clinically significant trends. RESULTS: Our results indicate that tissue dissociation followed by brief fixation in 1% paraformaldehyde and permeabilisation in 70% methanol produces a stable single cell suspension, which can subsequently be stained with a wide range of antibodies for the accurate identification of cells in a potentially heterogeneous tumour population. CONCLUSION: This technology can rapidly identify sub-populations of cells expressing differing levels of proteins, which may prove to be indicative of disease progression for this aggressive disease.

Antibodies, Monoclonal↗
PubMed1998

Clinical applications of chromosome analysis, from fine needle aspiration biopsies, of posterior uveal melanomas.

PURPOSE: An accurate assessment of prognosis is essential to the clinical assessment of malignancy. In posterior uveal melanoma specific chromosome alterations have been shown to correlate significantly with prognosis; but the procedure is restricted to patients treated surgically, and in consequence has been limited mainly to large tumours. Fine needle aspiration biopsy (FNAB) may provide sufficient material to perform this technique, and allow its use in the in situ assessment of tumours, including small lesions. To determine the feasibility of this approach we have conducted a pilot study using enucleated tumours. METHODS: Ten cases of posterior uveal melanoma were studied. In each instance both a test FNAB and a standard tissue preparation were conducted, and the results compared. FNABS were obtained from enucleated tumours by aspirating cells using a 5 ml syringe with a .25 gauge needle; cells were injected into phosphate-buffered saline, spun down and established in vitro. Conventional short-term cultures were established from tumour tissue samples, which were minced prior to the establishment of cultures. Cytogenetic analysis was performed following standard protocols. RESULTS: Of the 10 cases examined, full chromosome analysis was obtainable from all standard tissue short-term cultures. Cytogenetics was successful from cultures of 6 FNAB, with 2 further FNAB producing partial analyses. No major clonal differences were determined between the two procedures. CONCLUSIONS: Cytogenetic analysis of FNAB appears to be entirely feasible for posterior uveal melanomas, and may permit an accurate in situ assessment of tumours, including small lesions.

Aged↗
PubMed1998

Clinical and morphological features of Waardenburg syndrome type II.

Evaluation of 4-month-old girl who presented with congenital cataracts revealed heterochromia iridis, fundus hypopigmentation, residual white forelock and sensory neural hearing loss--findings consistent with Waardenburg syndrome type II. Bilateral peripheral iridectomies performed at lensectomy provided tissue for evaluation. Light microscopy revealed fewer melanocytes in the blue iris than in the brown. Electron microscopic examination showed a significant (p = 0.0001) reduction in melanosome size in the blue iris, and the nerve endings contained fewer vesicles. A defect in neural crest cell migration and melanin synthesis may be responsible for the heterochromia iridis seen in Waardenburg syndrome type II.

Cataract↗
PubMed1998

Health-promoting behaviors of rural adolescent women.

A part of a larger study of the health behaviors of adolescent women, this investigation examined health-promoting behaviors and the influence of cognitive, social, and environmental factors on these health-promoting behaviors of rural adolescent women. The sample consisted of 128 rural African-American and white adolescent women. Forty-four percent of the variance in health-promoting behavior of this sample was explained by five variables: self-image, problem solving, mother's education, employment status, and family structure. Self-image was the most salient predictor of health-promoting behavior, explaining 33% of the variance.

Adolescent↗