Search PubMed⌕ Search

Biomedical subjects

P Smith

Publications and source records attributed to P Smith.

At least 253 records · Page 14Linked to original sources
PubMed1998

Differential production of apoptosis-modulating proteins in patients with hypertrophic burn scar.

BACKGROUND: The biochemical and cellular pathways resulting in the production of proliferative scar in the thermally injured patient remain incompletely elucidated. A promising area of investigation is the phenomenon of programmed cell death and its modulation. The following study was designed to quantify differential levels of the bcl-2 protooncogene and the Fas cell surface receptor, two apoptosis-modulating proteins, in the peripheral blood mononuclear cell (PBMC) fractions of burn patients with hypertrophic scar versus those considered to have healed normally. The study also encompassed an immunohistochemical examination of fibroblasts in vitro, to identify differential levels of Fas, bcl-2, and interleukin converting enzyme (ICE). METHODS: PBMC fractions were isolated from two matched burn patient cohorts of 10 patients each, the experimental group carrying the clinical and histopathologic diagnosis of hypertrophic burn scar. The supernatant from each mitogenically stimulated specimen was halved and subjected to the Fas/APO-1 enzyme-linked immunosorbent assay (ELISA) and the bcl-2 ELISA. Results for each assay were compared between groups by unpaired t tests. Further biopsy specimens of isolated proliferative scar were used in vitro to analyze the role of these apoptosis-modulating proteins and ICE. This immunoperoxidase technique was analyzed qualitatively. RESULTS: The expression of the bcl-2 protein in the PBMC fractions of the burn patients with hypertrophic scar is significantly elevated in comparison to the control cohort (307.72 +/- 72.29 u/ml vs 31.55 +/- 6.73 u/ml; P = 0.0042). The quantitative levels of the Fas receptor did not differ significantly between the groups, respectively (0.3988 +/- 0.179 u/ml vs 0.2899 +/- 0.066 u/ml; P = 0.5787). Immunoperoxidase staining of proliferative scar fibroblasts and those from surrounding skin revealed relatively decreased levels of membrane-bound Fas and ICE. bcl-2 was not detectable in these specimens. CONCLUSIONS: Differential expression of the bcl-2 protooncogene and the Fas cell surface receptor in the PBMC fraction of patients with burn injuries may suggest a disequilibrium in a complex biochemical signaling mechanism mediating programmed cell death. The increased levels of bcl-2 could be responsible for delayed fibroblast apoptosis, resulting in the disruption of normal healing and subsequent hypertrophic scarring. This is confirmed by an in vitro examination of wound fibroblasts versus those from surrounding uninjured skin. This immunoperoxidase technique reveals a localized relative decrease in Fas and ICE, two apoptosis-inducing proteins, at the level of the fibroblast in the proliferative scar specimen.

Adult↗
PubMed1998

Sodium channel protein expression enhances the invasiveness of rat and human prostate cancer cells.

Expression of Na+ channel protein was analysed in established cell lines of rat and human prostatic carcinoma origin by flow cytometry using a fluorescein-labelled polyclonal antibody. In many cell lines examined, the obtained frequency distribution profiles were bimodal and identified a subpopulation of cells which expressed high levels of Na+ channel protein. A significant positive correlation was demonstrated between the proportion of channel-expressing cells and the functional ability of individual cell lines to invade a basement membrane matrix in vitro. In addition, two transfectant cell lines containing rat prostate cancer genomic DNA were found to express significantly elevated levels of Na+ channel protein when compared with the original benign recipient cell line. Enhanced Na+ channel expression by two metastatic derivatives of these transfectant cells directly correlated with increased invasiveness in vitro. These studies strongly support the hypothesis that expression of Na+ channel protein and the metastatic behaviour of prostatic carcinoma cells are functionally related, either by endowing the membranes of these cells with specialised electrophysiological properties (e.g. enhancing their motility and/or secretory activities) and/or by perturbing endogenous mechanisms regulating ionic homeostasis within the cells.

Animals↗
PubMed1998

Incorporation of photoluminescent polarizers into liquid crystal displays

Liquid crystal displays, the dominant flat panel display technology, are limited in brightness and energy efficiency because of the use of absorbing polarizers and color filters. Liquid crystal-based photoluminescent display devices have been fabricated that use thin, polarized photoluminescent layers that have highly anisotropic absorption or emission. These layers both polarize light and generate bright color. This approach can simplify device design and substantially increase device brightness, contrast, efficiency, and (in specific configurations) viewing angle.

Journal Article↗
PubMed1998

Type 1 and type 2 cytokine-producing mouse CD4+ and CD8+ T cells in acute Schistosoma mansoni infection.

CD4+ and CD8+ T cells can be divided based on the cytokines that they secrete into type 1 (Th1, Tc1) and type 2 (Th2, Tc2) subsets. Schistosoma mansoni infection in mice is characterized by a type 2-dominated response. We have used intracellular cytokine staining to demonstrate dramatic changes in the relative numbers of Tc1 and Th2 cells in the spleens of mice during acute schistosome infection. In infected mice prior to egg laying a generalized type 1 response dominated, and was associated with an expansion in the frequency of Tc1 and Th1 cells. By week 7 after infection the cytokine response was of type 2, with an increase in the numbers of Th2 cells and a dramatic reduction in the frequency of Tc1 cells. Following the onset of egg laying there was apoptosis of cells in the spleens of mice, with CD4+ and in particular CD8+ T cells undergoing apoptosis. The loss of CD8+ T cells may in part be attributable to the development of a type 2 environment, following egg laying, with type 2 responses mediating the apoptosis of Tc1 cells. Schistosome regulation of Tc1 during egg laying may be required to prevent type 1 inflammatory responses from exacerbating egg-induced pathology.

Animals↗
PubMed1998

Reaching those most in need: participation in a Planned Parenthood smoking cessation program.

We evaluated the representativeness of women approached and enrolled in a brief smoking cessation intervention conducted in Planned Parenthood clinics. In this effectiveness study, regular clinic staff were trained to identify, offer participation, and counsel willing smoking clients as part of their clinic visit. Chart audits were conducted to determine the percent of clients who had smoking status identified, as well as the percent and characteristics of potentially eligible clients who were not approached. Baseline and non-participant questionnaires were analyzed to determine participation rate and characteristics of those participating versus those not participating. Smoking status was documented in 99% of charts. Seventy percent of eligible smokers were approached about study participation and 74% of those approached participated. There were no significant differences between those approached and those not approached or between those who participated versus those who did not on a host of sociodemographic variables. This project was able to approach and attract a representative sample of young, lower income women to participate in a brief, clinic-based smoking cessation program.

Adolescent↗
PubMed1998

Outcome after aneurysmal subarachnoid haemorrhage: the use of a graphical model in the assessment of risk factors.

In 102 consecutive prospectively identified patients with subarachnoid haemorrhage (SAH) we have analysed the severity of the initial haemorrhage and the direct and indirect effects of adverse factors on outcome. The data we recorded included delay in diagnosis, risk groups, Doppler measurements, angiographic findings, surgical events and outcome at 1 year. By using a temporal graphical chain model, the associations between all variables and possible causal pathways were statistically determined. The severity of the initial haemorrhage, as determined by means of a clinical assessment and CT scanning, allowed low-, medium- and high-risk patient groups and a statistically predictable outcome to be identified. The overall management mortality was 13.7% at 1 year; 70.6% had a favourable outcome and 15.7% were severely disabled. Outcome was directly associated with risk group (p = 0.0038) and rebleeding (p = 0.0000). Delayed diagnosis led to a poorer outcome (p = 0.014)--an indirect association probably due to rebleeding. Adverse surgical events led to a significantly poorer outcome in high-risk patients. No significant relationship was found either between age and risk group (p = 0.7784) or between age and outcome (p = 0.6418). Preoperative clinical (WFNS) grade was unreliable in predicting outcome. It is the particular risk group, determined by the initial SAH, that indicates the individual patient's outcome. Management strategies can reduce preventable adverse events such diagnostic delay and rebleeding. Future studies should stratify patients according to risk group, delay in diagnosis and rebleeding in order to enable a clearer comparison to be made of treatment methods.

Adult↗
PubMed1998

Morphometric analysis of developing crowns of maxillary primary second molars and permanent first molars in humans.

The purpose of this study was firstly to characterize the changes occurring in size and form of the mineralizing maxillary second primary molar and first permanent molar crowns, and secondly to determine if similar changes in size and form characterize enamel apposition in the crowns of these teeth. Twenty-five primary second molars and 20 maxillary permanent first molars at various stages of development, found in archaeological excavations in Israel, were examined for a number of measured variables using image analyser software. Teeth were divided into two groups according to their stage of development: stage I included all teeth at an early stage of development in which mesiobuccal-cusp height was less than 5 mm for the primary molar and 5.9 mm for the permanent molar; stage 2 included all teeth in later stages of development where mesiobuccal-cusp height was greater than these values. In the primary molar, a significant increase was found between the two stages in almost all variables. Significant correlations were also found between all intercusp distances and the external variables. Strong correlations between height of the mesiobuccal cusp and all external and internal variables were noted in stage 1, but fewer in stage 2. In the permanent tooth, no increase was observed in intercusp distances and very few correlations were found between and among the variables. The results suggest that a change in the shape of the maxillary primary second molar occurs during formation, with the lingual cusp tips moving lingually and distally, and the distobuccal cusp tips moving distally. No change occurs in the shape of the maxillary permanent first molar during crown formation. Growth of the maxillary primary second and permanent first molar crowns occurs in 'bursts' of development.

Age Determination by Teeth↗
PubMed1998

Ultracytochemical localization of hydrogen peroxide production by dental plaque bacteria.

This study looked for evidence of in vitro hydrogen peroxide (HP) synthesis in human dental plaque, using an ultracytochemical technique that included incubation in a CeCl3-rich medium. Supragingival dental plaque was obtained from periodontally healthy individuals and subgingival dental plaque from human periodontal disease sites. Specificity of the cytochemical reaction was demonstrated using catalase (as HP scavenger). HP production was indicated by an electron-dense precipitate localized at the cell envelope of unidentified gram-positive and gram-negative bacteria in both supra- and subgingival samples. The ultracytochemical reaction localized the HP production primarily to the plasma membrane and periplasmic space.

Adult↗
PubMed1998

Prostatic stromal cell phenotype is directly modulated by norepinephrine.

OBJECTIVES: To evaluate the response of prostatic stromal cells in vitro to the action of the agonist norepinephrine and to examine the role of cell density in this response. METHODS: Stromal cells isolated from transurethral chippings of patients with benign prostatic hyperplasia (BPH) were seeded onto tissue culture dishes either at high density (9 x 10(3) cells/cm2) or at low density (1.5 x 10(3) cells/cm2). Norepinephrine was added at concentrations in the range of 2.5 to 50 microM. Cells were harvested at the moment of confluence, labeled with monoclonal antibodies to four cytoskeletal proteins, and analyzed by flow cytometry. RESULTS: Sparsely plated stromal cells showed a consistent biphasic response in which a small fall in immunofluorescence occurred in the range of 5 to 15 microM norepinephrine but was thereafter followed by a progressive rise in fluorescence to 50 microM, indicating increased expression of smooth-muscle-associated cytoskeletal proteins. The shape of flow-cytometric frequency-distribution histograms for smooth-muscle myosin, desmin, and talin suggested that all mesenchymal cells in the stromal cultures were similarly modulated by norepinephrine. However, the effect on smooth-muscle actin was different in that a subpopulation of hyperreactive cells was identified. Densely plated stromal cells did not show a similar biphasic response to norepinephrine but instead demonstrated an overall downward trend, indicating a progressively diminished expression of these cytoskeletal proteins. CONCLUSIONS: Norepinephrine stimulation directly modulates BPH-derived prostatic stromal cells toward a differentiated smooth-muscle phenotype as evidenced by increased expression of cytoskeletal proteins. The effect of norepinephrine on cultures is cell-density-dependent, suggesting that intercellular communication is an important factor in coordinating the differentiation responses. This study has revealed a specific interaction between physical and humoral stimuli, which influences in part the phenotype of prostatic stromal cells. Such interaction is likely to determine the development of clinical BPH, and also the response of any individuals following therapeutic intervention using selective alpha-adrenergic blockade.

Cell Count↗
PubMed1998

Tumour grade does not change between primary and recurrent mammary carcinoma.

The primary tumour grade in 115 patients with infiltrating ductal carcinoma of the breast was compared with the type of the ductal carcinoma in situ (DCIS) component and with the grade of 169 locally recurrent and metastatic lesions. 102 patients had axillary lymph node metastases at the time of primary surgery, 49 had subsequent recurrences and 36 had both. There was concordance of grade between the primary tumour and axillary lymph node metastases and with subsequent locally recurrent and metastatic lesions. The type of the DCIS component was also significantly associated with the grade of the infiltrating component. No evidence of progression of tumour grade between these phases of mammary carcinoma was found.

Breast Neoplasms↗
PubMed1998

Maximising the world wide web for high quality educational and clinical support to health and medical professionals in rural areas.

Attracting and retaining medical and allied health professionals to rural and remote regions is a perennial problem, world-wide. It is exacerbated by the associated problem of providing high quality, cost-effective educational and clinical support to health professionals and trainees located in such areas. The world wide web is being used as a tool to address these twin problems to provide a means of communication, interaction and educational and clinical support to geographically dispersed and isolated pools of users. An interactive electronic notice board has been developed as a clinical problems' discussion forum to act as a venue for critical debate about clinical issues and to provide a searchable archive of information to assist in the management of clinical problems. A description of the forum will demonstrate the potential of the world wide web as a learning and a clinical support tool.

Australia↗
PubMed1998

Cell proliferation measured by MIB1 and timing of surgery for breast cancer.

We have investigated the use of the antibody MIB1 as a proliferative and prognostic marker in breast cancer and whether changes in proliferative activity could account for differences in prognosis of premenopausal women operated on during different phases of the menstrual cycle. MIB1 expression was strongly correlated with S-phase fraction and histological grade. There was no difference in MIB1 scores between different phases of the menstrual cycle. Both MIB1 score and timing of surgery correlated significantly with duration of survival, while the two together were even stronger predictors of overall survival. Women with slowly proliferating tumours surgically removed in the luteal phase had a very good prognosis, whereas women with rapidly proliferating tumours excised at other times of the cycle had a worse prognosis.

Adult↗
PubMed1998

Antibodies to heat-shock protein 27 are associated with improved survival in patients with breast cancer.

The overexpression of the heat-shock proteins hsp90, hsp70 and hsp27 in human mammary carcinomas has previously been shown to correlate with reduced overall survival. Moreover, antibodies to hsp90 were detectable in the serum of a large proportion of breast cancer patients but they were not found in normal controls. High antibody levels also correlated with reduced survival. Here, we show that antibodies to hsp27 were also detectable in the sera from breast cancer patients but not from normal controls, whereas antibodies to hsp70 were detectable in approximately one-third of both groups. The presence of antibodies to hsp27 was correlated with an improved rather than a reduced survival, particularly beyond the first 5 years. Hence, the overexpression of hsps in breast cancer cells does not provoke a generalized immune response to all the hsps. Moreover, the presence of antibodies to different hsps has distinct associations with survival. These effects are discussed in terms of the mechanisms that provoke an immune response to the hsps and the protective/non-protective effects of such a response.

Antibodies↗
PubMed1998

Time trends in breast cancer survival: experience in a single centre, 1975-89.

The aim of this retrospective cohort study was to investigate whether survival of patients with breast cancer has changed over the period 1975-89. A total of 2604 women diagnosed as having invasive breast cancer at a clinical oncology unit in London were followed up for between 5 and 20 years. Patients were divided into four groups according to menstrual status (pre or post) and the staging of cancer (operable or inoperable). For each group, survival from diagnosis was compared between three consecutive 5-year cohorts, both with and without adjustments made for relevant prognostic factors. No temporal patterns were found in patients with inoperable cancer, in whom the survival rate was consistently low. Of women with operable cancers, differences were seen only among post-menopausal women, for whom the best survival patterns were seen in patients diagnosed between 1985-89. This is probably due to tamoxifen being commonly prescribed as adjuvant treatment for this cohort of patients. We cannot explain an apparently worse survival in the group of patients presenting in the early 1980s compared with that observed in the late 1970s.

Adult↗
PubMed1998

Family history and survival in premenopausal breast cancer.

The clinicopathological characteristics of breast cancer in 95 women between the ages of 24 and 45 years with a family history of breast cancer were compared with tumours from 329 women with sporadic disease matched for age and year of diagnosis. There was a trend for the family history patients to have slightly smaller tumours (mean size 2.49 cm) than the controls (mean 3.04 cm) (Mann-Whitney test, P = 0.09). A significantly greater proportion of the familial cases had grade III infiltrating ductal carcinoma than did the controls (40% vs 27%; chi2(1) = 5.64, P = 0.02). Despite this, there were more cases of operable node-negative disease among the study group than among the controls (48% vs 32%; chi2(1) = 8.2, P = 0.004). There was a highly significant survival advantage for patients with a family history (chi2 = 22.4, P < 0.001). Five- and 10-year survival rates were 92% and 87% for those with a family history compared with 70% and 54% for those in the control group. This survival advantage was maintained when patients with operable disease only were considered. In multivariate analysis, which included age, tumour size, stage, histological grade and family history, family history was an independent predictor of favourable prognosis and, in a Cox model, was associated with a relative risk of survival of 6.11 (95% CI 2.81-13.28). These results suggest that familial breast cancer has a more favourable clinical course than the more common sporadic forms of the disease.

Adult↗
PubMed1998

Generation of metastatic variants by transfection of a rat non-metastatic epithelial cell line with genomic DNA from rat prostatic carcinoma cells.

Prostate cancer is the second leading cause of male death from malignant disease in Europe and in the USA. Failure to prevent or eliminate metastatic dissemination is a fundamental problem underlying the current inadequate treatment of prostate cancer, and novel therapeutic strategies are required if this disease is to be successfully managed. No independent markers are yet available to predict the behaviour of any individual prostate cancer, particularly its potential to metastasize, and there is now an urgent prerequisite to identify and characterize genes specifically involved in determining the metastatic phenotype of prostate cancer cells before any biologically appropriate treatment modality can be devised. To identify DNA sequences that trophically promote the metastatic phenotype, we have established a new transfection assay with which to monitor activity of prostate cancer genomic DNA. Rat prostatic G and AT6.1 cell lines derived from the same original Dunning R3327 rat prostatic carcinoma exhibit, respectively, low- and high-metastatic phenotypes when grown in syngeneic Copenhagen rats. Rat mammary epithelial cell line 'Rama 37' derived originally from Wistar-Furth rats yields benign non-metastasizing adenomas when inoculated subcutaneously into syngeneic animals. In this report, the Rama 37 cell line is successfully used as the recipient cell-line for transfected DNA fragments extracted from rat prostatic carcinoma G and AT6.1 cells. New metastatic variants of Rama 37 cells have been generated. Enzymatically fragmented genomic DNA from rat metastatic prostate carcinoma cell lines was co-transfected together with plasmid pSV2neo into parental Rama 37 cells, followed by culture in the presence of Geneticin-G418 to select for the transfected cells. To enable subsequent identification of metastasis-promoting DNA sequences, the fragmented genomic DNA sequences were covalently attached to specifically engineered linker DNA molecules to flank the genomic DNA before transfection. Thereafter, the resulting transfectants were pooled and inoculated into mammary fat pads of female Wistar-Furth rats. Metastases produced by the transfectant cells in vivo were reestablished from secondary tumours and probed for the presence of the specific synthetic oligonucleotide sequences that flanked, and hence identified, the presence of the transfected DNA. These new metastatic cells are shown to provide a sensitive assay system with which to detect DNA sequences responsible for conveying the metastatic phenotype of prostate cancer when inoculated into syngeneic rats.

Animals↗
PubMed1998

Clinical course and prognostic factors following bone recurrence from breast cancer.

Three hundred and sixty-seven women presenting to the Breast Unit at Guy's Hospital between 1975 and 1990 whose first distant metastasis was in the skeleton were identified and the influence of a number of patient and tumour characteristics on the development and subsequent prognosis of bone metastases was assessed. One hundred and thirty-nine women had disease that remained clinically confined to the skeleton. They were more likely to be older, with lobular carcinoma and to have presented initially with little or no axillary lymph node involvement. The 228 women who subsequently developed disease at extra-osseus sites were more likely to have poorly differentiated ductal tumours and heavy lymph node involvement at primary diagnosis. On multivariate analysis, the clinical and pathological factors of greatest prognostic importance for survival after the development of bone metastases were histological grade (P = < 0.0001), oestrogen receptor status (P = < 0.0001), bone disease at initial presentation (P = < 0.0001), disease-free interval (P = 0.002) and age (P = 0.006).

Adult↗