Roy Sanders - Academia.edu (original) (raw)
Papers by Roy Sanders
British Journal of Plastic Surgery, 1983
Clinical problem. Several clinical situations would benefit from enhanced angiogenesis, especiall... more Clinical problem. Several clinical situations would benefit from enhanced angiogenesis, especially to improve the take of skin equivalents. Understanding the interactions between endothelial cells and extracellular matrix components may offer new thepeutic strategies. Previously, we showed that microvascular endothelial cells in vitro show specific patterns of morphological response to different extracellular matrices; interstital collagen stimulates sprouting and migration, for which the integrin á2 subunit is critical, whereas laminin stimulates cord formation and tubulogensis, for which the integrin á6 subunit is critical. This raises the hypothesis that angiogenesis is regulated by a specific integrin signal. Methods. Cultures of microvascular endothelial cells were (passages 7 and 34) were overlaid with gelling solutions of collagen or Matrigel, and were treated with inhibitors of signalling pathways (cytochalsin D, colchicine, Y27632, ML7 and PP2) or with siRNA for signalling genes. The activation of downstream proteins (src, ERK1/2 and myosin light chain) was analysed by Western blotting and immunostaining. Results. The effects of specific inhibitors of cytoskeletal reorganisation showed that the á2 response is completely tubulin-dependent, whereas á6 is mainly actin-and myosin light chain kinase-dependent. Analysis of phospho-myosin light chain, showed decreased levels with á2 and elevated levels with á6, and also differences in subcellular localisation. No difference in activation of the ERK1/2 between á2 and á6 were found, but src-family kinase activation was greater with á2 than á6, being localised to large adhesion plaques, but diffusely in the cell cords formed in Matrigel. Conclusions. The morphological responses of endothelial cells depend on cytoskeletal reorganisation anchored to cell-matrix and cell-cell adhesion complexes. Collectively, these data help to define specific differences between á2 and á6 signals. The different patterns of cytoskeletal organisation and myosin light chain activation correlated with distinct integrin signals. Also, src family kinases, but not ERK1/2 are preferentially activated through á2, resulting in the disruption of cell-cell adhesions involved in migratory behaviour. These findings may allow the design of improved dermal equivalent matrices to support angiogenesis, and possible pharmacologic targets for neovascularisation.
The sprouting and migratory responses of human microvascular endothelial cells to collagen depend... more The sprouting and migratory responses of human microvascular endothelial cells to collagen depend on the integrin α2β1. These responses were blocked by the inhibitor PP2 (50-800nM), suggesting dependence on src-family kinase (SFK) activity. Phospho-src levels were increased in response to collagen or integrin α2β1 ligation and were localised to large focal adhesions, but decreased and relatively diffuse in response to Matrigel. siRNA probes designed for c-src and fyn were shown to suppress the morphological responses to collagen. This effect of SFK appears to be specific for collagen responses because neither PP2 nor siRNA to src or fyn suppress tubulogenic responses of endothelial cells to laminin. These results indicate that SFK activated via α2 but not α6 integrins mediates angiogenic sprouting in HPMEC. Matrix-integrin-specific signals represent novel, independent mechanisms of regulating angiogenesis.
Journal of Vascular Research
ABSTRACT
Lasers in Medical Science, 2001
Studies reported to date have shown a good depilatory response from patients treated with the nor... more Studies reported to date have shown a good depilatory response from patients treated with the normal mode ruby laser (NMRL) over 12 weeks, but a low response over a time period greater than this. Previous publications have suggested that this could be accounted for by the apparently poor skin penetration of laser light and so this study attempted to assess whether this was indeed the case. Skin samples of varying thicknesses were taken from six Caucasian patients and their depths measured. Each was laid individually on an energy meter before having pulses from an NMRL compatible with clinical doses (4.75 J/cm2, 9.24 J/cm2 and 13.41 J/cm2) fired on the epidermis. Several samples had the laser fired repetitively on the surface to assess whether this caused any change in laser/skin fluence depth profiles. Repetitive firing of the NMRL on the epidermis of skin samples did not alter the energy recorded by the meter beneath. The fluence/depth profiles were constructed showing the majority of energy was lost within the first 1 mm of the skin surface (50%) which then further reduced over distance but at a much slower rate. The maximum depth of penetration was 14.8 mm (SD +/- 0.478) which appeared to be a function of wavelength and not fluence. The results suggest that laser penetration of skin should be adequate for generating enough heat at the hair bulge and bulb, potentially causing permanent damage. The implications of this study are that it is probably the presence of the correct chromophore in large enough amounts which is required for successful permanent depilation to occur.
Journal of Plastic, Reconstructive & Aesthetic Surgery, 2006
The treatment of keloid and hypertrophic scars remains difficult. Enzymatic digestion of keloid s... more The treatment of keloid and hypertrophic scars remains difficult. Enzymatic digestion of keloid scars has been previously proposed as an effective treatment strategy for reducing the volume of keloid scars. To test this, we administered intra-lesional injections of pure collagenase (between 600 and 4500 units for each scar) into the keloid and hypertrophic scars of seven human volunteers (five keloid and two hypertrophic scars). Five patients (three keloid and two hypertrophic) received more than one injection of collagenase. The treatment resulted in a temporary reduction in scar volume for three of the patients with keloid scars. However, scar volumes for these three patients returned to the same (or greater) levels after 6 months of follow-up. Treatment with collagenase produced no change in scar volume for the two patients with hypertrophic scar. Side effects were numerous and severe including; pain, swelling, blistering, ulceration and ecchymosis at the site of injection. One patient required admission to hospital for 48 h after the first injection. Maximum length of follow-up was 6 months. None of the seven patients completed the study and returned for final follow-up at 2 years. This pilot study suggests that treatment of keloid and hypertrophic scars with intra-lesional injections of collagenase is ineffective.
British Journal of Plastic Surgery, 2001
Normal-mode ruby laser (NMRL) irradiation of skin has now become an acceptable method of producin... more Normal-mode ruby laser (NMRL) irradiation of skin has now become an acceptable method of producing depilation. However, side effects, which include superficial burning and changes in skin pigmentation, still occur and, although temporary, can be distressing to the patient. This paper reports a method by which the skin can be protected (or preconditioned) from damage during NMRL treatment by pre-heating to a lower, non-damaging level prior to irradiation. Using the black-haired mouse (C57B1/10) as an animal model, an appropriate 'preconditioning' temperature was established by exposing the mouse skin to a range of temperatures, taking biopsies and staining the skin immunohistochemically for heat shock protein 70 (HSP 70) expression within the keratinocyte cells. Increased HSP 70 expression is stimulated by exposure to environmental stressors such as heat, so it was hypothesised that its increased expression conveyed increased cellular protection. The appropriate temperature (45 degrees C for 15 min) allowed for the superficial skin cells to be protected (as assessed by maximal HSP 70 staining) but undamaged (as assessed by haematoxylin and eosin staining), leaving the target hair-producing cells unprotected. Eight mice (16 flanks) were then exposed to this preconditioning temperature (eight of the flanks being growing-hair sites and eight resting-hair sites) and 5 h later exposed to a laser fluence known to cause mild skin damage and depilation (6J/cm2). This exposure was to both the preconditioned and the adjacent non-preconditioned sites. A statistically significant reduction in skin damage (P <0.001), as measured by the time taken to heal and noted both clinically and histologically, was seen in the preconditioned sites in resting-hair regions but not in growing-hair regions. Depilation, established over an 8 week period, was successful in growing-hair regions within both preconditioned and non-preconditioned sites, but complete hair regrowth had occurred in preconditioned and non-preconditioned sites within resting-hair regions by 5 weeks. The latter finding was consistent with work already reported suggesting that NMRL-assisted depilation in this animal model is not successful for hairs in the telogen phase. Successful preconditioning of mouse skin prior to laser exposure appears to reduce NMRL-induced skin side effects. In addition, the technique does not appear to adversely affect successful depilation.
British Journal of Plastic Surgery, 2002
The c-myc oncogene has been shown to be overexpressed in a number of malignancies, and may play a... more The c-myc oncogene has been shown to be overexpressed in a number of malignancies, and may play an important role in the pathogenesis of malignant melanoma. Previous prognostic studies have demonstrated c-myc overexpression in a range of cutaneous melanomas, and levels of c-myc oncoprotein expression have been shown to correlate with clinical outcome in both primary and secondary disease. The purpose of this study was to investigate the in vitro manipulation of c-myc expression using antisense oligonucleotides. The human melanoma cell lines A375M, Bel 1 and WM115 were treated with c-myc antisense oligonucleotides, and the cellular growth was compared with controis. Antisense oligonucleotides reduced the growth rate of all three cell lines, and produced a reduction in c-myc gene expression as measured by flow cytometry. The growth inhibitions in the A375M, Bel 1 and WM115 cell lines at 72 h were 36.6%, 35.8% and 29.3%, respectively. Each of these was significantly different from control cultures (P < 0.01). The c-myc antisense produced a mean 75% reduction in c-myc oncoprotein expression when compared with controls in the A375M cells (P < 0.001), a 49% reduction in the Be 11 cells (P < 0.001) and a 28% reduction in the WM 115 cells (P = 0.005). This study demonstrates the importance of the c-myc oncogene in controlling melanoma growth. It suggests that blocking the expression of this gene, using an antisense approach, reduces melanoma cell growth, and may potentially provide a novel gene-therapy strategy for the treatment of advanced melanoma. 9
European Journal of Surgical Oncology (EJSO), 2006
We report a prospective study examining the prognostic significance of the c-myc oncoprotein, p53... more We report a prospective study examining the prognostic significance of the c-myc oncoprotein, p53 tumour suppressor gene and proliferation rate measurements in malignant melanoma. Methods: Flow cytometry (FCM) was used to measure the expression of c-myc, p53 and proliferation parameters in patients who had received an injection of the thymidine analogue bromodeoxyuridine prior to surgery. Results: Sixty-seven patients had successful FCM measurements of the three parameters. c-myc was detected in 97% of patients with a median cell positivity of 62%. The median p53 positivity was 13%. The median potential doubling time (T pot ) of the tumours wasf 9.4 days. In univariate analysis, each of the parameters showed an association with survival in metatstatic disease with rapid proliferation (pZ0.006) or overexpression of c-myc (pZ0.038) related to poor survival whereas increased positivity for p53 predicted better survival (pZ0.013). Conclusions: These data indicate that laser cytometric technology can be used to obtain quantitative data on oncoproteins expression and cell proliferation rates in clinical samples of malignant melanoma. q
Burns, 2008
Hospitals NHS Trust, UK b u r n s 3 4 ( 2 0 0 8 ) 1 6 4 -1 7 4
Melanoma Research, 1997
Wolters Kluwer Health may email you for journal alerts and information, but is committed to maint... more Wolters Kluwer Health may email you for journal alerts and information, but is committed to maintaining your privacy and will not share your personal information without your express consent. For more information, please refer to our Privacy Policy. ... Skip Navigation Links Home > 1997 - ...
Annals of Plastic Surgery, 2000
... Topping, Adam FRCS(Ed); Linge, Claire PhD; Gault, David FRCS; Grobbelaar, Addie FRCS(plast); ... more ... Topping, Adam FRCS(Ed); Linge, Claire PhD; Gault, David FRCS; Grobbelaar, Addie FRCS(plast); Sanders, Roy FRCS. ... Topping A, Linge C, Gault D, Grobbelaar A, Sanders R. A review of the ruby laser with reference to hair depilation. Ann Plast Surg 2000;44:668-674. ...
Annals of Plastic Surgery, 2000
Although it is proposed that heat is the cause of follicular damage leading to depilation, this h... more Although it is proposed that heat is the cause of follicular damage leading to depilation, this has never been proved. This study aims to determine the mode by which depilation is effected and, if heat is the mechanism, what temperatures are reached within treated follicles and if sufficient damage is produced therein. Two excised specimens of hair-bearing skin from 5 patients undergoing facelifts were dissected to reveal the hair bulbs/shafts on the deep surface. They were placed on a jig, and one pulse from a normal-mode ruby laser (NMRL) of 15 J per square centimeter was fired on the epidermal surface. A thermal imaging camera recorded dermal temperature changes on the deep surface in real time. Specimens were then examined histologically for the site and extent of cellular damage by immunohistochemical staining for a protein marker of cell damage (p53). The NMRL targeted hair follicles specifically. The most common follicular temperature increase ranged from 5 to 10 degrees C. In specimens from 1 patient the increase was more than 30 degrees C (p < 0.001). Heat dissipation into interfollicular tissue in all specimens occurred 2 seconds after exposure. Evidence of laser-induced damage to follicle-lining cells was found only in those follicles with damaged hair shafts. The changes were found to a greater depth (to the bulb) and greater extent (beyond the bulge) in those follicles reaching higher temperatures. These findings suggest that the NMRL should produce permanent depilation. The variability between follicles and between patients explains, perhaps, the uneven outcome regarding depilation using the NMRL. Success appears to depend on peak follicular temperatures achieved during laser exposure, which may result from the follicular characteristics of the individual patient.
Journal of Orthopaedic Trauma, 2010
Journal of Clinical Pathology, Nov 1, 1999
Aims-To investigate the histopathological reporting of basal cell carcinoma. Methods-Methods of c... more Aims-To investigate the histopathological reporting of basal cell carcinoma. Methods-Methods of classification and attitudes to excision margins were ascertained from histopathologists in 130 centres; 82 replies were obtained (63% response rate). Results-24% of those replying did not use any classification system for basal cell carcinoma. The remainder (76%) used a wide variety of diVerent classification systems. A small number (9%) of those questioned felt reporting on completeness of excision was not important. The majority of histopathologists considered the excision margin was worth reporting but there were diVerences in methods of processing and reporting biopsies. Conclusions-There is considerable variation in histopathological reporting of basal cell carcinoma. There is a need for uniformity of histopathological reporting to allow both improved management decisions and comparative audit of this extremely common skin cancer. (J Clin Pathol 1999;52:867-869)
J Orthop Trauma, 1997
... and Planning College of Architecture and Planning University of Colorado, Boulder, Cu, USA 80... more ... and Planning College of Architecture and Planning University of Colorado, Boulder, Cu, USA 80309-314 { lewin@ucsub, ehrhardt@ucsu, mdg ... that display an elevated shelf (see figure 5). These renderings were produced collaboratively with (then Ph.D. student) Scott Simmons. ...
Annals of Plastic Surgery, Mar 1, 1999
Several clinical studies on the efficacy of ruby laser-assisted hair removal have reported that r... more Several clinical studies on the efficacy of ruby laser-assisted hair removal have reported that regrowth of hair after treatment is common. One of the reasons for the regrowth of hair is the incomplete destruction of germinative hair cells due to the insufficient penetration of the ruby laser in the skin. It was the aim of this study to estimate the extent of damage to the hair follicles after one ruby laser treatment and to determine whether the ruby laser destroyed the bulbs and the bulge regions of hair follicles. The extent of laser damage in hair shafts was determined by serial examination of six specimens of ex vivo scalp skin lasered with the Chromos 694 Depilation Ruby Laser at 14 J per square centimeter and 20 J per square centimeter. Another nine specimens of ex vivo scalp skin were similarly lasered, and monoclonal antibody LP2K was used to identify the bulge regions of the hair follicles using the immunoperoxidase technique. Damage to the bulge region was assessed from consecutive specimens, which were stained with hematoxylin-eosin stain. The mean depth of laser damage sustained by hair follicles was 1.34 mm (14 J per square centimeter) and 1.49 mm (20 J per square centimeter) underneath the skin surface. Most of the laser damage involved the bulge regions but fell short of the hair bulbs. The laser damage did not seem to extend far enough down the hair shafts to result in permanent hair destruction. The clinical implications of this finding are discussed.
British Journal of Plastic Surgery, 1983
Clinical problem. Several clinical situations would benefit from enhanced angiogenesis, especiall... more Clinical problem. Several clinical situations would benefit from enhanced angiogenesis, especially to improve the take of skin equivalents. Understanding the interactions between endothelial cells and extracellular matrix components may offer new thepeutic strategies. Previously, we showed that microvascular endothelial cells in vitro show specific patterns of morphological response to different extracellular matrices; interstital collagen stimulates sprouting and migration, for which the integrin á2 subunit is critical, whereas laminin stimulates cord formation and tubulogensis, for which the integrin á6 subunit is critical. This raises the hypothesis that angiogenesis is regulated by a specific integrin signal. Methods. Cultures of microvascular endothelial cells were (passages 7 and 34) were overlaid with gelling solutions of collagen or Matrigel, and were treated with inhibitors of signalling pathways (cytochalsin D, colchicine, Y27632, ML7 and PP2) or with siRNA for signalling genes. The activation of downstream proteins (src, ERK1/2 and myosin light chain) was analysed by Western blotting and immunostaining. Results. The effects of specific inhibitors of cytoskeletal reorganisation showed that the á2 response is completely tubulin-dependent, whereas á6 is mainly actin-and myosin light chain kinase-dependent. Analysis of phospho-myosin light chain, showed decreased levels with á2 and elevated levels with á6, and also differences in subcellular localisation. No difference in activation of the ERK1/2 between á2 and á6 were found, but src-family kinase activation was greater with á2 than á6, being localised to large adhesion plaques, but diffusely in the cell cords formed in Matrigel. Conclusions. The morphological responses of endothelial cells depend on cytoskeletal reorganisation anchored to cell-matrix and cell-cell adhesion complexes. Collectively, these data help to define specific differences between á2 and á6 signals. The different patterns of cytoskeletal organisation and myosin light chain activation correlated with distinct integrin signals. Also, src family kinases, but not ERK1/2 are preferentially activated through á2, resulting in the disruption of cell-cell adhesions involved in migratory behaviour. These findings may allow the design of improved dermal equivalent matrices to support angiogenesis, and possible pharmacologic targets for neovascularisation.
The sprouting and migratory responses of human microvascular endothelial cells to collagen depend... more The sprouting and migratory responses of human microvascular endothelial cells to collagen depend on the integrin α2β1. These responses were blocked by the inhibitor PP2 (50-800nM), suggesting dependence on src-family kinase (SFK) activity. Phospho-src levels were increased in response to collagen or integrin α2β1 ligation and were localised to large focal adhesions, but decreased and relatively diffuse in response to Matrigel. siRNA probes designed for c-src and fyn were shown to suppress the morphological responses to collagen. This effect of SFK appears to be specific for collagen responses because neither PP2 nor siRNA to src or fyn suppress tubulogenic responses of endothelial cells to laminin. These results indicate that SFK activated via α2 but not α6 integrins mediates angiogenic sprouting in HPMEC. Matrix-integrin-specific signals represent novel, independent mechanisms of regulating angiogenesis.
Journal of Vascular Research
ABSTRACT
Lasers in Medical Science, 2001
Studies reported to date have shown a good depilatory response from patients treated with the nor... more Studies reported to date have shown a good depilatory response from patients treated with the normal mode ruby laser (NMRL) over 12 weeks, but a low response over a time period greater than this. Previous publications have suggested that this could be accounted for by the apparently poor skin penetration of laser light and so this study attempted to assess whether this was indeed the case. Skin samples of varying thicknesses were taken from six Caucasian patients and their depths measured. Each was laid individually on an energy meter before having pulses from an NMRL compatible with clinical doses (4.75 J/cm2, 9.24 J/cm2 and 13.41 J/cm2) fired on the epidermis. Several samples had the laser fired repetitively on the surface to assess whether this caused any change in laser/skin fluence depth profiles. Repetitive firing of the NMRL on the epidermis of skin samples did not alter the energy recorded by the meter beneath. The fluence/depth profiles were constructed showing the majority of energy was lost within the first 1 mm of the skin surface (50%) which then further reduced over distance but at a much slower rate. The maximum depth of penetration was 14.8 mm (SD +/- 0.478) which appeared to be a function of wavelength and not fluence. The results suggest that laser penetration of skin should be adequate for generating enough heat at the hair bulge and bulb, potentially causing permanent damage. The implications of this study are that it is probably the presence of the correct chromophore in large enough amounts which is required for successful permanent depilation to occur.
Journal of Plastic, Reconstructive & Aesthetic Surgery, 2006
The treatment of keloid and hypertrophic scars remains difficult. Enzymatic digestion of keloid s... more The treatment of keloid and hypertrophic scars remains difficult. Enzymatic digestion of keloid scars has been previously proposed as an effective treatment strategy for reducing the volume of keloid scars. To test this, we administered intra-lesional injections of pure collagenase (between 600 and 4500 units for each scar) into the keloid and hypertrophic scars of seven human volunteers (five keloid and two hypertrophic scars). Five patients (three keloid and two hypertrophic) received more than one injection of collagenase. The treatment resulted in a temporary reduction in scar volume for three of the patients with keloid scars. However, scar volumes for these three patients returned to the same (or greater) levels after 6 months of follow-up. Treatment with collagenase produced no change in scar volume for the two patients with hypertrophic scar. Side effects were numerous and severe including; pain, swelling, blistering, ulceration and ecchymosis at the site of injection. One patient required admission to hospital for 48 h after the first injection. Maximum length of follow-up was 6 months. None of the seven patients completed the study and returned for final follow-up at 2 years. This pilot study suggests that treatment of keloid and hypertrophic scars with intra-lesional injections of collagenase is ineffective.
British Journal of Plastic Surgery, 2001
Normal-mode ruby laser (NMRL) irradiation of skin has now become an acceptable method of producin... more Normal-mode ruby laser (NMRL) irradiation of skin has now become an acceptable method of producing depilation. However, side effects, which include superficial burning and changes in skin pigmentation, still occur and, although temporary, can be distressing to the patient. This paper reports a method by which the skin can be protected (or preconditioned) from damage during NMRL treatment by pre-heating to a lower, non-damaging level prior to irradiation. Using the black-haired mouse (C57B1/10) as an animal model, an appropriate 'preconditioning' temperature was established by exposing the mouse skin to a range of temperatures, taking biopsies and staining the skin immunohistochemically for heat shock protein 70 (HSP 70) expression within the keratinocyte cells. Increased HSP 70 expression is stimulated by exposure to environmental stressors such as heat, so it was hypothesised that its increased expression conveyed increased cellular protection. The appropriate temperature (45 degrees C for 15 min) allowed for the superficial skin cells to be protected (as assessed by maximal HSP 70 staining) but undamaged (as assessed by haematoxylin and eosin staining), leaving the target hair-producing cells unprotected. Eight mice (16 flanks) were then exposed to this preconditioning temperature (eight of the flanks being growing-hair sites and eight resting-hair sites) and 5 h later exposed to a laser fluence known to cause mild skin damage and depilation (6J/cm2). This exposure was to both the preconditioned and the adjacent non-preconditioned sites. A statistically significant reduction in skin damage (P <0.001), as measured by the time taken to heal and noted both clinically and histologically, was seen in the preconditioned sites in resting-hair regions but not in growing-hair regions. Depilation, established over an 8 week period, was successful in growing-hair regions within both preconditioned and non-preconditioned sites, but complete hair regrowth had occurred in preconditioned and non-preconditioned sites within resting-hair regions by 5 weeks. The latter finding was consistent with work already reported suggesting that NMRL-assisted depilation in this animal model is not successful for hairs in the telogen phase. Successful preconditioning of mouse skin prior to laser exposure appears to reduce NMRL-induced skin side effects. In addition, the technique does not appear to adversely affect successful depilation.
British Journal of Plastic Surgery, 2002
The c-myc oncogene has been shown to be overexpressed in a number of malignancies, and may play a... more The c-myc oncogene has been shown to be overexpressed in a number of malignancies, and may play an important role in the pathogenesis of malignant melanoma. Previous prognostic studies have demonstrated c-myc overexpression in a range of cutaneous melanomas, and levels of c-myc oncoprotein expression have been shown to correlate with clinical outcome in both primary and secondary disease. The purpose of this study was to investigate the in vitro manipulation of c-myc expression using antisense oligonucleotides. The human melanoma cell lines A375M, Bel 1 and WM115 were treated with c-myc antisense oligonucleotides, and the cellular growth was compared with controis. Antisense oligonucleotides reduced the growth rate of all three cell lines, and produced a reduction in c-myc gene expression as measured by flow cytometry. The growth inhibitions in the A375M, Bel 1 and WM115 cell lines at 72 h were 36.6%, 35.8% and 29.3%, respectively. Each of these was significantly different from control cultures (P < 0.01). The c-myc antisense produced a mean 75% reduction in c-myc oncoprotein expression when compared with controls in the A375M cells (P < 0.001), a 49% reduction in the Be 11 cells (P < 0.001) and a 28% reduction in the WM 115 cells (P = 0.005). This study demonstrates the importance of the c-myc oncogene in controlling melanoma growth. It suggests that blocking the expression of this gene, using an antisense approach, reduces melanoma cell growth, and may potentially provide a novel gene-therapy strategy for the treatment of advanced melanoma. 9
European Journal of Surgical Oncology (EJSO), 2006
We report a prospective study examining the prognostic significance of the c-myc oncoprotein, p53... more We report a prospective study examining the prognostic significance of the c-myc oncoprotein, p53 tumour suppressor gene and proliferation rate measurements in malignant melanoma. Methods: Flow cytometry (FCM) was used to measure the expression of c-myc, p53 and proliferation parameters in patients who had received an injection of the thymidine analogue bromodeoxyuridine prior to surgery. Results: Sixty-seven patients had successful FCM measurements of the three parameters. c-myc was detected in 97% of patients with a median cell positivity of 62%. The median p53 positivity was 13%. The median potential doubling time (T pot ) of the tumours wasf 9.4 days. In univariate analysis, each of the parameters showed an association with survival in metatstatic disease with rapid proliferation (pZ0.006) or overexpression of c-myc (pZ0.038) related to poor survival whereas increased positivity for p53 predicted better survival (pZ0.013). Conclusions: These data indicate that laser cytometric technology can be used to obtain quantitative data on oncoproteins expression and cell proliferation rates in clinical samples of malignant melanoma. q
Burns, 2008
Hospitals NHS Trust, UK b u r n s 3 4 ( 2 0 0 8 ) 1 6 4 -1 7 4
Melanoma Research, 1997
Wolters Kluwer Health may email you for journal alerts and information, but is committed to maint... more Wolters Kluwer Health may email you for journal alerts and information, but is committed to maintaining your privacy and will not share your personal information without your express consent. For more information, please refer to our Privacy Policy. ... Skip Navigation Links Home > 1997 - ...
Annals of Plastic Surgery, 2000
... Topping, Adam FRCS(Ed); Linge, Claire PhD; Gault, David FRCS; Grobbelaar, Addie FRCS(plast); ... more ... Topping, Adam FRCS(Ed); Linge, Claire PhD; Gault, David FRCS; Grobbelaar, Addie FRCS(plast); Sanders, Roy FRCS. ... Topping A, Linge C, Gault D, Grobbelaar A, Sanders R. A review of the ruby laser with reference to hair depilation. Ann Plast Surg 2000;44:668-674. ...
Annals of Plastic Surgery, 2000
Although it is proposed that heat is the cause of follicular damage leading to depilation, this h... more Although it is proposed that heat is the cause of follicular damage leading to depilation, this has never been proved. This study aims to determine the mode by which depilation is effected and, if heat is the mechanism, what temperatures are reached within treated follicles and if sufficient damage is produced therein. Two excised specimens of hair-bearing skin from 5 patients undergoing facelifts were dissected to reveal the hair bulbs/shafts on the deep surface. They were placed on a jig, and one pulse from a normal-mode ruby laser (NMRL) of 15 J per square centimeter was fired on the epidermal surface. A thermal imaging camera recorded dermal temperature changes on the deep surface in real time. Specimens were then examined histologically for the site and extent of cellular damage by immunohistochemical staining for a protein marker of cell damage (p53). The NMRL targeted hair follicles specifically. The most common follicular temperature increase ranged from 5 to 10 degrees C. In specimens from 1 patient the increase was more than 30 degrees C (p < 0.001). Heat dissipation into interfollicular tissue in all specimens occurred 2 seconds after exposure. Evidence of laser-induced damage to follicle-lining cells was found only in those follicles with damaged hair shafts. The changes were found to a greater depth (to the bulb) and greater extent (beyond the bulge) in those follicles reaching higher temperatures. These findings suggest that the NMRL should produce permanent depilation. The variability between follicles and between patients explains, perhaps, the uneven outcome regarding depilation using the NMRL. Success appears to depend on peak follicular temperatures achieved during laser exposure, which may result from the follicular characteristics of the individual patient.
Journal of Orthopaedic Trauma, 2010
Journal of Clinical Pathology, Nov 1, 1999
Aims-To investigate the histopathological reporting of basal cell carcinoma. Methods-Methods of c... more Aims-To investigate the histopathological reporting of basal cell carcinoma. Methods-Methods of classification and attitudes to excision margins were ascertained from histopathologists in 130 centres; 82 replies were obtained (63% response rate). Results-24% of those replying did not use any classification system for basal cell carcinoma. The remainder (76%) used a wide variety of diVerent classification systems. A small number (9%) of those questioned felt reporting on completeness of excision was not important. The majority of histopathologists considered the excision margin was worth reporting but there were diVerences in methods of processing and reporting biopsies. Conclusions-There is considerable variation in histopathological reporting of basal cell carcinoma. There is a need for uniformity of histopathological reporting to allow both improved management decisions and comparative audit of this extremely common skin cancer. (J Clin Pathol 1999;52:867-869)
J Orthop Trauma, 1997
... and Planning College of Architecture and Planning University of Colorado, Boulder, Cu, USA 80... more ... and Planning College of Architecture and Planning University of Colorado, Boulder, Cu, USA 80309-314 { lewin@ucsub, ehrhardt@ucsu, mdg ... that display an elevated shelf (see figure 5). These renderings were produced collaboratively with (then Ph.D. student) Scott Simmons. ...
Annals of Plastic Surgery, Mar 1, 1999
Several clinical studies on the efficacy of ruby laser-assisted hair removal have reported that r... more Several clinical studies on the efficacy of ruby laser-assisted hair removal have reported that regrowth of hair after treatment is common. One of the reasons for the regrowth of hair is the incomplete destruction of germinative hair cells due to the insufficient penetration of the ruby laser in the skin. It was the aim of this study to estimate the extent of damage to the hair follicles after one ruby laser treatment and to determine whether the ruby laser destroyed the bulbs and the bulge regions of hair follicles. The extent of laser damage in hair shafts was determined by serial examination of six specimens of ex vivo scalp skin lasered with the Chromos 694 Depilation Ruby Laser at 14 J per square centimeter and 20 J per square centimeter. Another nine specimens of ex vivo scalp skin were similarly lasered, and monoclonal antibody LP2K was used to identify the bulge regions of the hair follicles using the immunoperoxidase technique. Damage to the bulge region was assessed from consecutive specimens, which were stained with hematoxylin-eosin stain. The mean depth of laser damage sustained by hair follicles was 1.34 mm (14 J per square centimeter) and 1.49 mm (20 J per square centimeter) underneath the skin surface. Most of the laser damage involved the bulge regions but fell short of the hair bulbs. The laser damage did not seem to extend far enough down the hair shafts to result in permanent hair destruction. The clinical implications of this finding are discussed.