Search PubMed⌕ Search

Biomedical subjects

S Prince

Publications and source records attributed to S Prince.

At least 19 recordsLinked to original sources

Use of ulcer size and initial responses to treatment to predict the healing time of leg ulcers.

OBJECTIVE: To test the following two hypotheses: the initial healing profiles of individual leg ulcers determine the longer-term outcome; healing time can be predicted from an initial ulcer size measurement and a sequence of further measurements recorded after treatment has started. METHOD: Twenty-three patients with venous leg ulcers were studied (10 male, 13 female). Digital images of the ulcers were taken at weekly intervals; ulcer size was measured electronically and the information stored in an electronic patient record. The healing profile for each ulcer was analysed by linear regression using the correlation coefficient (r) to indicate linearity. For [r] > 0.85 ([r] = modulus of r, [where r is negative], that is good linearity and hence wound healing), the predicted healing time was calculated from the initial size (cm2) and initial healing rate (cm2/week), and was compared with the actual healing time. RESULTS: The majority of ulcers (17/23) healed with linearity ([r] > 0.85). For these ulcers there was agreement between the predicted healing time and the actual healing time (correlation coefficient 0.95). CONCLUSION: Venous ulcers that respond to treatment appear to heal at a near constant rate. The initial response to treatment can be used to reliably estimate the healing time.

Aged↗

Insulin-like growth factor ligands, receptors, and binding proteins in cancer.

This review aims to summarize experimental evidence supporting the role of the insulin-like growth factor (IGF) signalling system in the progression, maintenance, and treatment of cancer. These data implicate the IGF system as an important modifier of cancer cell proliferation, survival, growth, and treatment sensitivity. The role of the IGF system in cancer should be examined in the context of the extra-cellular and intra-cellular signalling networks, in particular: phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt/PKB), mammalian target of rapamycin (mTOR), and forkhead transcription factors (FOXO). This review highlights evidence derived from molecular structure and functional genetics with respect to how the extra-cellular components of the IGF system function normally, and their subsequent modifications in cancer. The therapeutic relevance of the research evidence described is also addressed, as the challenge is to apply this knowledge to human health.

Amino Acid Sequence↗

Disinfection with 10% povidone-iodine versus 0.5% chlorhexidine gluconate in 70% isopropanol in the neonatal intensive care unit.

AIM: The finding that 10% povidone-iodine skin disinfectant may compromise thyroid function in premature infants prompted its replacement with 0.5% chlorhexidine gluconate solution in 70% isopropanol. The objective of this study was to compare the incidence rates of true infection and contamination associated with the use of these two disinfectants in the neonatal intensive care unit. METHODS: The study population comprised two cohorts of infants admitted to our neonatal intensive care unit: 1) in 1992-1993 when only 10% povidone-iodine was used as a skin disinfectant, and 2) in 1995-1996 when only 0.5% chlorhexidine gluconate solution in 70% isopropanol was used. A retrospective chart review was conducted to determine whether all documented positive blood, CSF and suprapubic aspirate cultures indicated true infection or contamination. True infection was defined as clinical symptoms and/or laboratory abnormalities suggestive of sepsis, with positive blood, CSF or suprapubic aspirate cultures. RESULTS: 1146 infants were admitted during the study periods, 507 during the first period and 639 during the second. In the early group, 17.6% of infants had major malformations, 72.0% were premature and 25.2% had weights of < 1500 g. Corresponding percentages for the latter group were 16.0%, 80.6% and 32.9%, respectively. No statistically significant differences were found between the two research periods in rate of infants with positive blood cultures, true infections, or contamination. CONCLUSION: The use of 0.5% chlorhexidine gluconate solution in 70% isopropanol as a skin disinfectant is justified in neonatal intensive care units because it is not associated with an increased incidence of infections as opposed to 10% povidone-iodine and is devoid of detrimental effects.

Anti-Infective Agents, Local↗

Activation of fibronectin gene expression by hepatitis B virus x antigen.

The development of fibrosis and cirrhosis during chronic hepatitis B virus (HBV) infection correlates with the persistent expression of HBV x antigen (HBxAg), which acts in part, by stimulating selected signal transduction pathways, including nuclear factor kappa B (NF-kappa B). To identify NF-kappa B responsive genes that are differentially expressed in HBxAg-positive cells, HepG2 cells were stably transfected with HBxAg, and then with pZeoSV2 or pZeoSV2-I kappa B alpha. When RNAs from each culture were compared by PCR-select cDNA subtraction, fibronectin (FN) mRNA was shown to be strongly down-regulated by I kappa B alpha. Up-regulated expression of FN and co-expression between FN and HBxAg were observed in liver sections from HBV carriers that were stained for HBxAg and analysed for FN mRNA by in situ hybridization (ISH). In liver cell cultures, HBxAg increased the levels of FN mRNA and protein. This was because of the HBxAg-mediated trans-activation of the FN promoter, which was NF-kappa B-dependent. HBxAg also antagonized the repression of the FN promoter by the tumour suppressor, p53. Hence, the FN gene may be a natural target for HBxAg trans-activation, perhaps through activation of NF-kappa B and inactivation of p53, thereby contributing to the accumulation of FN in the liver over the course of chronic HBV infection.

Cell Line↗

Stimulation of melanogenesis by tetradecanoylphorbol 13-acetate (TPA) in mouse melanocytes and neural crest cells.

In vitro studies have shown that the phorbol ester, 12-tetradecanoylphorbol 13-acetate (TPA) induces neural crest cell differentiation into melanocytes, and stimulates proliferation and differentiation of normal melanocytes. As TPA is not a physiological agent, its action is clearly mimicking some in vivo pathway involved in these processes. An understanding of the effect of TPA on the expression of melanogenic genes will therefore provide valuable insight into the molecular mechanisms regulating melanocyte differentiation. In this study, we utilized primary cultures of neural crest cells and an immortalized melanocyte cell line (DMEL-2) which proliferates in the absence of TPA, to explore the effects of TPA on key melanogenic effectors. In neural crest cells, TPA was found to be necessary for both microphthalmia associated transcription factor (Mitf) up-regulation and for melanin synthesis. Using northern blots, we show that in DMEL-2 cells, TPA significantly increases the messenger ribonucleic acid (mRNA) levels of the tyrosinase gene family (tyrosinase, Tyrp1 and Dct) and the expression of Mitf. Western blots demonstrate that in these TPA-treated cells there is a concomitant increase in Tyr, Tyrp1 and glycosylated Dct protein levels. Pax3, a known Mitf regulator, is unaltered by TPA treatment. This study demonstrates the utility of a novel cell line for investigating the long-term effects of TPA on melanogenesis and provides an understanding of how TPA enhances mouse melanocyte differentiation.

Animals↗

Beating heart surgery reduces mortality in the reoperative bypass patient.

BACKGROUND: Reoperative coronary artery bypass grafting (redo-CABG) has an increased operative morbidity and mortality compared to patients undergoing primary revascularization. In an effort to reduce the hazards of reoperative CABG, we commenced revascularizing selected patients without cardiopulmonary bypass (CPB) as an alternative to conventional approaches. METHODS: From January 1998 to Dec. 2000, 432 patients underwent reoperative CABG, 153 patients (35%) without the aid of CPB. Treatment groups were compared by means of univariate analysis for preoperative risk factors and postoperative complications. Predicted risk and risk-adjusted mortality were determined by the Society of Thoracic Surgeons risk algorithm. RESULTS: There was a significant difference in the preoperative predicted risk scores between the two treatment groups (off pump 6.5% vs. on pump 5.4%, p=0.0343). There was a significant difference in the off pump observed mortality (2.61%) versus the on pump group (9.68%, p=0.0065). Decreased morbidity in the off pump group was evidenced by a reduced need for blood products (25% vs. 67%, p<0.0001), and the incidence of prolonged ventilation (4% vs. 14%, p=0.0032). The off pump group also had shorter hospital stays (6.2 +/- 5.96 days vs. 8.0 +/- 7.82, p=0.0091). No significant differences between the two groups were seen in the prevalence of perioperative myocardial infarction, stroke, renal failure, or reoperation for bleeding. CONCLUSION: Bypass grafting without CPB significantly decreases mortality and morbidity in selected reoperative patients, and should be considered a viable alternative to conventional approaches.

Analysis of Variance↗

SV-40 large T antigen reversibly inhibits expression of tyrosinase, TRP-1, TRP-2 and Mitf, but not Pax-3, in conditionally immortalized mouse melanocytes.

Transformation of mouse melanocytes with a variety of exogenous oncogenes or chemical carcinogens frequently results in irreversible loss of pigmentation. We have infected mouse melanocytes with a temperature-sensitive mutant of the simian virus 40 (SV40) large tumour antigen to study the molecular mechanisms underlying depigmentation during melanocyte transformation. The results show that, out of six cell lines analyzed at the permissive temperature of the oncoprotein, three epidermal and two dermal melanocyte clones remained pigmented and retained the ability to synthesize melanin and to express the melanocyte-specific genes, including tyrosinase, tyrosinase related protein-1, tyrosinase related protein-2 and Mitf. In contrast, one dermal melanocyte clone (DMEL-3) gradually depigmented. This depigmentation was characterized by enhanced growth and down-regulation of melanocyte-specific gene expression. When the oncogene was inactivated by culture at the non-permissive temperature, the pigmented phenotype in DMEL-3 cells could be rescued, and there was a corresponding time-dependent increase in melanocyte-specific gene expression. After extended passage, this rescue could not be achieved. Our results provide direct evidence for the role of the SV40 large T antigen in melanocyte de-differentiation. Expression of Pax-3, a transcription factor implicated in melanocyte differentiation, was unaltered during the SV40-initiated de-differentiation, and de-differentiated melanocytes expressed normal levels of Pax-3 message. We speculate on the mechanism by which the oncoprotein might be regulating Mitf gene expression and of the role of Pax-3 in this process.

3T3 Cells↗

Qualitative methodologies and community participation in examining reproductive experiences: the Harlem Birth Right Project.

OBJECTIVES: Racial disparities in health present a challenge to public health because of the complexity of interacting social forces. The Harlem Birth Right Project sought to improve understanding of these forces by using qualitative and community participatory methods. In this paper we 1) describe the process of qualitative inquiry and community involvement, 2) evaluate the impact of community participation, and 3) present a brief summary of the findings on social context as it relates to pregnancy outcomes of women in Harlem. METHODS: We operationalized the qualitative method by combining participant observation, longitudinal case studies, and focus groups. An ethnographic survey was used to verify and triangulate findings across methods of data collection. We involved the community in the design, implementation, and analysis by collaborating with community-based organizations, setting up a community advisory board, and the use of dialogue groups and community meetings. RESULTS: The use of qualitative methods and community partnership uncovered important aspects of the social context of women's lives that may not have emerged through traditional epidemiologic research. We found that pregnancy may serve as a catalyst to increase perception of the magnitude of preexisting social stressors. Several stressors and chronic strains associated with structural forces were identified. For example, the high percentage of households headed by women is seen as one consequence of larger structural forces. While social support networks serve as an important coping mechanism to buffer against the stress caused by these structural forces, the types of support women seek differs by social strata, and some strategies were identified as being substantially more effective than others. CONCLUSIONS: Qualitative and community participatory research can be successfully conducted to support public health goals and can derive important new information on the social context of women's lives.

Community Participation↗

The integration of orientation information in the motion correspondence problem.

We examine how differently oriented components contribute to the discrimination of motion direction along a horizontal axis. Stimuli were two-frame random-dot kinematograms that were narrowband filtered in spatial frequency. On each trial, subjects had to state whether motion was to the left or the right. For each stimulus condition, Dmax (the largest displacement supporting 80% correct direction discrimination performance) was measured. In experiment 1, Dmax was measured for orientationally narrowband stimuli as a function of their mean orientation. Dmax was found to increase as the orientation of the stimuli became closer to the axis of motion. Experiment 2 used isotropic stimuli in which some orientation bands contained a coherent motion signal, and some contained only noise. When the noise band started at vertical orientations and increased until only horizontal orientations contained a coherent motion signal, Dmax increased slightly. This suggests that near-vertical orientations interfere with motion perception at large displacements when they contain a coherent motion signal. When the noise band started at horizontal and increased until only vertical orientations contained the motion signal, Dmax decreased steadily. This implies that Dmax depends at least partly on the most horizontal motion signal in the stimulus. These results were contrasted with two models. In the first, the visual system utilises the most informative orientations (nearest horizontal). In the second, all available orientations are used equally. Results supported an intermediate interpretation, in which all orientations are used but more informative ones are weighted more heavily.

Discrimination, Psychological↗

False positivity of enzyme-linked immunosorbent assay for measurement of secretory IgA antibodies directed at HIV type 1 antigens.

We have determined that polymeric IgA in saliva of HIV-1-uninfected individuals binds in varying degrees to components of culture supernatants containing HIV-1 recombinant proteins when ELISA is used for the determination. This finding did not extend to salivary IgG antibodies. Further, such problems were not encountered in Western blot. Binding did not appear to be mediated by salivary proteins known to bind to IgA, including secretory component, amylase, lactoferrin, lysozyme, galactosyl transferase, or secretory leukocyte protease inhibitor, and was not influenced by blocking reagents or by changes in secondary anti-IgA antibodies. Although these findings will not likely impact on the use of saliva as a diagnostic fluid for HIV-1 infection (the HIV-1 response in saliva is mostly of the IgG isotype), they indicate that assessments of this secretion as an indicator of IgA mucosal immune responses to HIV-1 vaccines should be undertaken with caution.

Animals↗

Squamous carcinoma of the tongue: review.

Carcinoma of the tongue is a common condition treated by oral and maxillofacial surgeons. The tongue is a complex anatomical site at the entrance of the oropharynx, bounded by the floor of mouth and lingual mandibular cortex; its form and mobility are crucial for efficient swallowing; speech, and the appreciation of taste. Single and multiple treatments have been used, but the tongue remains a difficult area to assess and treat. In this paper, we have attempted to review some of the papers published over the last 20 years with particular reference to prognosis and functional outcome. We have dealt exclusively with squamous cell carcinoma of the tongue and its management by surgery, radiotherapy, brachytherapy, photodynamic therapy, and chemotherapy.

Carcinoma, Squamous Cell↗

Pigment-pigment interactions and energy transfer in the antenna complex of the photosynthetic bacterium Rhodopseudomonas acidophila.

BACKGROUND: Photosynthesis starts with the absorption of solar radiation by antenna pigment molecules. In purple bacteria these chromophores, (bacteriochlorophyll a and carotenoid) are embedded in the membrane; they are non-covalently bound to apoproteins which have the ability to modulate the chromophores' absorbing characteristics. The first structure of the bacterial antenna complex from Rhodopseudomonas acidophila, strain 10050, shows a ring of nonameric symmetry. Two concentric cylinders of apoproteins enclose the pigment molecules. The current resolution of the structure, to 2.5 A, allows us to begin to explore the mechanism of energy transfer among these pigments. RESULTS: The mechanism of energy transfer, from the short- to long-wavelength-absorbing pigments, is largely determined by the relative distances and orientations of the chromophores. In this paper we provide evidence that energy transfer between the B800 and B850 bacteriochlorophylls is largely via Förster induced dipole-dipole resonance. Strong Coulombic (exciton) coupling among the 18 short distanced chromophores in the B850 macrocycle is promoted by good alignment of the Qy dipoles. Singlet-singlet energy transfer from carotenoid to the B800 macrocycle appears to be minimal, with most of the energy transfer going to B850. The higher energy state of both chromophores dominates in more complex situations. CONCLUSIONS: The structure of the antenna complex not only shows Nature at its most aesthetic but also illustrates how clever and efficient the energy transfer mechanism has become, with singlet-singlet excitation being passed smoothly down the spectral gradient to the reaction centre.

Bacterial Proteins↗

A simple, rapid micro-latex fixation test.

A micro-latex fixation test (LFT) for the determination of rheumatoid factor (RF) is presented. Its advantages compared to similar tests are greater precision, simplicity, increased sensitivity, lower cost, reproducibility and adaptibility to large-scale testing. Micro-LFT titres are presented from a wide range of sample populations. The majority of normal samples show measureable titres whereas rheumatoid patients show high titres. A large sampling of pre- and post-transplant sera from kidney patients was studied and the micro-LFT titres were in the range of normal persons. The transplant sera were tested for lymphocytotoxic antibodies and no correlation was observed with the micro-LFT titres.

Adult↗

A plastic intraoral device for the collection of human parotid saliva.

A plastic intraoral (IO) cup developed to facilitate collection of human parotid saliva was tested on two groups of patients. Samples collected in both IO and tubed cups exhibited no significant differences in lysozyme or lactoperoxidase activity, levels of total protein or secretory IgA, or in flow rates. Results suggest that the IO cup provides a simple, reliable method for collecting parotid saliva.

Humans↗