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Biomedical subjects

J R Lupton

Publications and source records attributed to J R Lupton.

At least 19 recordsLinked to original sources
PubMed2001

Erbium:YAG cutaneous laser resurfacing.

The short-pulsed Er:YAG laser system is an excellent ablative tool for cutaneous resurfacing. This system is most efficacious for patients with milder cutaneous involvement, including mild photoinduced facial rhytides, mildly atrophic scars, and textural changes caused by fibrosis and dermatochalasis. The Er:YAG laser cannot achieve the same dramatic clinical and histologic improvements produced with the CO2 laser but does offer some distinct advantages that make it a valuable addition to the laser surgeon's armamentarium. The Er:YAG laser, because of its higher affinity for water-containing tissues, effects a much finer level of tissue ablation. Although erbium laser resurfacing results in decreased postoperative morbidity with a shorter recovery period, it cannot effect the same degree of improvement in photodamaged skin as can the CO2 laser. Excellent results, however, can be achieved with this laser, up to 50% or more overall clinical improvement, in patients with milder photodamage and scarring (Glogau classes I and II). In darker-skinned patients, the Er:YAG laser is often the preferred treatment modality. Continued research in the field has already led to the development of longer-pulsed Er:YAG lasers, which offer a compromise between the CO2 laser and the short-pulsed Er:YAG lasers in terms of clinical benefits while maintaining the safety profile of the traditional short-pulsed system. In addition, many surgeons now use a combination approach with the CO2 and Er:YAG lasers in an effort to maximize collagen contraction in certain areas and limit postoperative morbidity. As more research is conducted within the field of cutaneous resurfacing, newer systems will be developed in the continuing effort to create the ideal laser system--one which ameliorates the signs of photoaging without risk of major side effects or significant postoperative recovery.

Anesthesia↗
PubMed2001

Anatomical site-specific response to DNA damage is related to later tumor development in the rat azoxymethane colon carcinogenesis model.

There is now general agreement that the etiology of proximal and distal colon cancers may differ, thus prompting renewed interest in understanding anatomical site-specific molecular mechanisms of tumor development. Using a 2x2x2 factorial design with male Sprague-Dawley rats (corn oil, fish oil; pectin, cellulose; plus or minus azoxymethane injection) we found a greater than 2-fold difference (P < 0.001) in tumor incidence proximally versus distally (prox/dist ratio: corn oil, 2.25; fish oil, 2.61). The purpose of the present study was to determine if the higher degree of proximal versus distal tumors in our model system could be accounted for by differences between these two sites in initial DNA damage, response to that damage or an effect of diet at one site but not the other. DNA damage was assessed by quantitative immunohistochemistry of O(6)-methylguanine adducts; repair by measurement of O(6)-methylguanine-DNA alkyltransferase and removal was determined by measurement of targeted apoptosis. Although overall initial DNA damage was similar at both sites, in the distal colon there was a greater expression of repair protein (P < 0.001) and a greater degree of targeted apoptosis (P < 0.0001). There was also a reduction in DNA damage in the distal colon of rats consuming fish oil. Together, these results suggest that the lower tumor incidence in the distal colon may be a result of the capacity to deal with initial DNA damage by the distal colon, as compared with the proximal colon. Therefore, the determination of site-specific mechanisms in tumor development is important because distinct strategies may be required to protect against cancer at different sites.

Adenocarcinoma↗
PubMed2001

n-6 and n-3 polyunsaturated fatty acids differentially modulate oncogenic Ras activation in colonocytes.

Ras proteins are critical regulators of cell function, including growth, differentiation, and apoptosis, with membrane localization of the protein being a prerequisite for malignant transformation. We have recently demonstrated that feeding fish oil, compared with corn oil, decreases colonic Ras membrane localization and reduces tumor formation in rats injected with a colon carcinogen. Because the biological activity of Ras is regulated by posttranslational lipid attachment and its interaction with stimulatory lipids, we investigated whether docosahexaenoic acid (DHA), found in fish oil, compared with linoleic acid (LA), found in corn oil, alters Ras posttranslational processing, activation, and effector protein function in young adult mouse colon cells overexpressing H-ras (YAMC-ras). We show here that the major n-3 polyunsaturated fatty acid (PUFA) constituent of fish oil, DHA, compared with LA (an n-6 PUFA), reduces Ras localization to the plasma membrane without affecting posttranslational lipidation and lowers GTP binding and downstream p42/44(ERK)-dependent signaling. In view of the central role of oncogenic Ras in the development of colon cancer, the finding that n-3 and n-6 PUFA differentially modulate Ras activation may partly explain why dietary fish oil protects against colon cancer development.

Alkyl and Aryl Transferases↗
PubMed2001

Lasers in dermatology. An overview of types and indications.

Advances in laser technology have been so marked over the past two decades that successful eradication of many cutaneous pathologies and congenital defects, including vascular and pigmented lesions, tattoos, scars, and unwanted hair, can now be fully realized. Because of the relative ease with which many of these lesions can be removed, coupled with a low incidence of adverse postoperative sequelae, demand for laser surgery has increased substantially. In this review, the currently available laser systems with cutaneous application are outlined, with special reference to recent advancements and modifications in laser technology that have greatly expanded the laser surgeon's armamentarium and improved upon overall treatment efficacy.

Forecasting↗
PubMed2000

Effect of diet on colonic-programmed cell death: molecular mechanism of action.

Colon cancer evolves from a progressive inhibition of apoptosis and is influenced strongly by diet. Among dietary factors, butyrate (derived from fermentable fibers) may have utility as a chemopreventive agent because of its ability to promote apoptosis. Because CD95 (APO-1/Fas) transduces signals resulting in apoptosis, we tested the hypothesis that butyrate-dependent colonocyte apoptosis is mediated by this death receptor. Treatment of immortalized mouse colon cells with Fas agonistic antibody induced cell death, indicating that Fas in colonocytes is functional. Antagonism of Fas signaling using a soluble Fas:Fc chimera blocked butyrate induction of apoptosis. Therefore, Fas receptor dependent signal transduction is required for butyrate induction of apoptosis in colonic cells.

Animals↗
PubMed2000

Successful treatment of treatment-resistant laser-induced pigment darkening of a cosmetic tattoo.

BACKGROUND AND OBJECTIVE: Cosmetic tattoo removal has a reported risk of immediate pigment darkening when treated with a high energy, nanosecond pulsed-laser system. Surgical treatment options for this reaction are limited and carry significant risk of scarring and permanent pigment alterations. This report describes the response of a resistant Q-switched ruby laser-induced cosmetic tattoo ink darkening to multiple treatments with the Q-switched alexandrite laser and Q-switch Nd:YAG laser and textural improvement with the UltraPulse CO(2) laser. STUDY DESIGN/MATERIALS AND METHODS: A woman with Q-switched ruby laser-induced pigment darkening of a cosmetic tattoo of the upper lip resistant to four further treatments with the ruby laser and two chemical peels received a total of 26 treatments with the Q-switched alexandrite and Nd:YAG lasers and a single treatment with the UltraPulse CO(2) laser, most treatments being done at monthly intervals. RESULTS: Treatment of the affected areas with the Q-switched alexandrite and Nd:YAG lasers resulted in complete clearing of the pigment without scarring, but revealed some preexisting textural changes. Use of the UltraPulse CO(2) laser smoothed the surface irregularities. CONCLUSION: The Q-switched pigment lasers are a useful modality for treating this pigment darkening reaction. As in this case, multiple treatment sessions with the laser may be necessary but the pigment can be expected to clear eventually without scarring. Any textural changes may be blended with the UltraPulse CO(2) laser with further improvement.

Adult↗
PubMed2000

Cutaneous hypersensitivity reaction to injectable hyaluronic acid gel.

BACKGROUND: Injectable hyaluronic acid gel is a non-animal biomaterial used for soft tissue augmentation. OBJECTIVE: The dermal implantation of this naturally occurring polysaccharide is reported to be well tolerated by patients, with a longer duration in tissue than bovine collagen without any major local or systemic side effects. We report a case of an acute hypersensitivity reaction in a woman after her third injection for improvement of melolabial fold wrinkles. METHODS: An adverse granulomatous-like response to the intradermal injection of a modified hyaluronic acid gel is described. RESULTS: The patient developed indurated and erythematous papulocystic nodules in the melolabial folds bilaterally at the sites of injection. CONCLUSION: Injectable hyaluronic acid gel can be associated with severe allergic reactions and patients should be warned of this possible treatment side effect.

Acute Disease↗
PubMed2000

Segmental neurofibromatosis in association with nevus sebaceus of Jadassohn.

We describe an unusual case involving the simultaneous occurrence of segmental neurofibromatosis (Type V NF) in a patient with a large nevus sebaceus of Jadassohn in the same physical distribution. Causative mechanisms of development of these 2 genetic disorders have not been definitively linked. Factors producing these diseases probably involve similar tissues at the same point in development because both have been reported in association with central nervous system anomalies and have been classified among the neurocutaneous syndromes. This is a case of a nevus sebaceus occurring in association with and in the same physical distribution as segmental NF. These disorders most likely represent a spectrum of disease within the phakomatoses.

Facial Asymmetry↗
PubMed2000

An unusual presentation of dermatomyositis: the type Wong variant revisited.

We describe a 53-year-old white woman with dermatomyositis (DM) who had additional clinical findings of pityriasis rubra pilaris (type Wong dermatomyositis) with histopathologic features of both pityriasis rubra pilaris (PRP) and porokeratosis. Type Wong dermatomyositis was originally described in 11 patients by Wong in 1969 and has been reported in 5 additional patients. This is a rarely described phenomenon in which patients with DM develop cutaneous hyperkeratotic lesions that resemble PRP and histologically show follicular hyperkeratosis and hair follicle destruction. Arrector pilorum muscles also show degenerative findings and myositis. We believe that this is the first reported case of a patient with type Wong DM who also has clinical and histologic features suggestive of porokeratosis. This is important because of the association of adult-onset dermatomyositis with internal malignancy and the well-documented association of porokeratosis with immunosuppression. These clinical and histologic findings serve as markers for malignancy in patients with DM. These patients warrant a complete review of systems and investigation for age-appropriate neoplasms as well as close long-term follow-up by dermatologists to ensure that these cutaneous eruptions are not overlooked.

Dermatomyositis↗
PubMed2000

Morphodensitometric analysis of protein kinase C beta(II) expression in rat colon: modulation by diet and relation to in situ cell proliferation and apoptosis.

We have recently demonstrated that overexpression of PKC beta(II) renders transgenic mice more susceptible to carcinogen-induced colonic hyperproliferation and aberrant crypt foci formation. In order to further investigate the ability of PKC beta(II) to modulate colonocyte cytokinetics, we determined the localization of PKC beta(II) with respect to cell proliferation and apoptosis along the entire colonic crypt axis following carcinogen and diet manipulation. Rats were provided diets containing either corn oil [containing n-6 polyunsaturated fatty acids (PUFA)] or fish oil (containing n-3 PUFA), cellulose (non-fermentable fiber) or pectin (fermentable fiber) and injected with azoxymethane (AOM) or saline. After 16 weeks, an intermediate time point when no macroscopic tumors are detected, colonic sections were utilized for immunohistochemical image analysis and immunoblotting. Cell proliferation was measured by incorporation of bromodeoxyuridine into DNA and apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling. In the distal colon, PKC beta(II) staining was localized to the upper portion of the crypt. In comparison, proximal crypts had more (P < 0.05) staining in the lower tertile. AOM enhanced (P < 0.05) PKC beta(II) expression in all regions of the distal colonic crypt (upper, middle and lower tertiles). There was also an interaction (P < 0.05) between dietary fat and fiber on PKC beta(II) expression (corn/pectin > fish/cellulose, fish/pectin > corn/cellulose) in all regions of the distal colonic crypt. With respect to colonic cell kinetics, proliferation paralleled the increase in PKC beta(II) expression in carcinogen-treated animals. In contrast, apoptosis at the lumenal surface was inversely proportional to PKC beta(II) expression in the upper tertile. These results suggest that an elevation in PKC beta(II) expression along the crypt axis in the distal colon is linked to enhancement of cell proliferation and suppression of apoptosis, predictive intermediate biomarkers of tumor development. Therefore, select dietary factors may confer protection against colon carcinogenesis in part by blocking carcinogen-induced PKC beta(II) expression.

Animals↗
PubMed2000

Dietary fish oil reduces O6-methylguanine DNA adduct levels in rat colon in part by increasing apoptosis during tumor initiation.

There is epidemiological, clinical, and experimental evidence that dietary fish oil, containing n-3 polyunsaturated fatty acids, protects against colon tumor development. However, its effects on colonocytes in vivo remain poorly understood. Therefore, we investigated the ability of fish oil to modulate colonic methylation-induced DNA damage, repair, and deletion. Sprague Dawley rats were provided with complete diets containing either corn oil or fish oil (15% by weight). Animals were injected with azoxymethane, and the distal colon was removed 3, 6, 9, or 12 h later. Targeted apoptosis and DNA damage were assessed by cell position within the crypt using the terminal deoxynucleotidyl transferase-mediated nick end labeling assay and quantitative immunohistochemical analysis of O6-methylguanine adducts, respectively. Localization and expression of the alkyl group acceptor, O6-methylguanine-DNA-methyltransferase, was also determined. Lower levels of adducts were detected at 6, 9, and 12 h in fish oil- versus corn oil-fed animals (P < 0.05). In addition, fish oil supplementation had the greatest effect on apoptosis in the top one-third of the crypt, increasing the apoptotic index compared with corn oil-fed rats (P < 0.05). In the top one-third of the crypt, fish oil feeding caused an incremental stimulation of apoptosis as adduct level increased. In contrast, a negative correlation between apoptosis and adduct incidence occurred with corn oil feeding (P < 0.05). Diet had no main effect (all tertiles combined) on O6-methylguanine-DNA-methyltransferase expression over the time frame of the experiment. The enhancement of targeted apoptosis combined with the reduced formation of O6-methylguanine adducts may account, in part, for the observed protective effect of n-3 polyunsaturated fatty acids against experimentally induced colon cancer.

Analysis of Variance↗
PubMed2000

Can granuloma annulare evolve into cutaneous sarcoidosis?

We report the unique case of a 50-year-old African American female with pulmonary sarcoidosis who presented with a new ichthyosiform eruption symmetrically located on the anterior shins and surrounded by red, translucent, intradermal papules. A skin biopsy of a new red papule showed features consistent with granuloma annulare (GA) with positive mucin staining, and an older hyperpigmented papule showed classic dermal noncaseating granulomas consistent with sarcoidosis. Recent reports have clearly demonstrated GA occurring in association with sarcoidosis, but this is the first report that suggests that a GA lesion may develop into a sarcoidal granuloma. We propose that GA may act as a precursor lesion to the more mature sarcoidal granuloma. This case further underscores the importance of careful clinicopathologic correlation.

Anti-Inflammatory Agents↗
PubMed1999

Potential protective mechanisms of wheat bran fiber.

Experimental studies using high-fiber supplements show that of all the fibers tested, wheat bran is the most effective in protecting against colon tumor development. The mechanisms behind this protective effect have not been elucidated completely, and the effect is most likely multifactorial. Some mechanisms, such as luminal dilution of potential carcinogens and accelerated transit through the colon, are well established. The fermentation of wheat fiber to short-chain fatty acids--especially butyric, which has been shown to inhibit tumor growth in vitro--is documented, but interpretation of the data from animal studies and clinical trials is subject to debate. Several potential mechanisms, such as effects of phytochemicals and phytates contained in wheat bran, have not yet been explored.

Colonic Neoplasms↗
PubMed1999

Carcinogen and dietary lipid regulate ras expression and localization in rat colon without affecting farnesylation kinetics.

Epidemiological and experimental data suggest that dietary fiber and fat are major determinants of colorectal cancer. However, the mechanisms by which these dietary constituents alter the incidence of colon cancer have not been elucidated. Evidence indicates that dominant gain-of-function mutations short-circuit protooncogenes and contribute to the pathogenesis of cancer. Therefore, we began to dissect the mechanisms whereby dietary fat and fiber, fed during the initiation, promotion and progression stages of colon tumorigenesis, regulate ras p21 localization, expression and mutation frequency. Male Sprague-Dawley rats (140) were provided with corn oil or fish oil and pectin or cellulose plus or minus the carcinogen azoxymethane (AOM) in a 2 x 2 x 2 factorial design and killed after 34 weeks. We have previously shown adenocarcinoma incidence in these animals to be 70.3% (52/74) for corn oil + AOM and 56.1% (37/66) for fish oil + AOM (P < 0.05). Total ras expression as well as ras membrane:cytosol ratio was 4- to 6-fold higher in colon tumors than in mucosa from AOM- or saline-injected rats. Expression of ras in the mucosal membrane fraction was 13% higher for animals fed corn oil compared with fish oil feeding (P < 0.05), which is noteworthy since ras must be localized at the plasma membrane to function. The elevated ras membrane:cytosol ratio in tumors was not due to increased farnesyl protein transferase activity or prenylation state, as nearly all detectable ras was in the prenylated form. Phosphorylated p42 and p44 mitogen activated protein kinase (ERK) expression was two-fold higher in tumor extracts compared with uninvolved mucosa from AOM- and saline-injected rats (P < 0.05). The frequency of K-ras mutations was not significantly different between the various groups, but there was a trend toward a greater incidence of mutations in tumors from corn oil fed rats (85%) compared with fish oil fed rats (58%). Our results indicate that the carcinogen-induced changes in ras expression and membrane localization are associated with the in vivo activation of the ERK pathway. In addition, suppression of tumor development by dietary n-3 polyunsaturated fatty acids may be partly due to a combined effect on colonic ras expression, membrane localization, and mutation frequency.

Alkyl and Aryl Transferases↗
PubMed1999

Antagonism of CD95 signaling blocks butyrate induction of apoptosis in young adult mouse colonic cells.

There is great interest in utilizing butyrate as a chemopreventive agent for colon tumorigenesis because of its ability to promote apoptosis in colon tumor cell lines. Because CD95 (APO-1/Fas) transduces signals resulting in apoptosis, we tested the hypothesis that butyrate-dependent colonocyte apoptosis is mediated by this death receptor. Butyrate (1 mM) exposure for 24 h upregulated expression of Fas and its ligand in young adult mouse colon (YAMC) cells. To delineate the proapoptotic effect of butyrate and to avoid the confounding effects of detachment from the extracellular matrix, adherent cell apoptosis was monitored as loss of plasma membrane asymmetry and dissipation of mitochondrial membrane potential (DeltaPsi(mt)) by laser cytometry. Soluble Fas receptor protein (Fas:Fc chimera) and caspase inhibitors (z-VAD-fmk and z-IETD-fmk) blocked butyrate induction of apoptosis. Treatment with Fas agonistic antibody (clone Jo-2) significantly induced cell death, indicating that Fas in colonocytes is functional. In addition, butyrate promoted apoptosis by inducing loss of DeltaPsi(mt) and phospholipid asymmetry of the plasma membrane after 12 and 24 h of exposure, respectively, before cell detachment. Therefore, Fas receptor-dependent signal transduction is involved in butyrate induction of apoptosis in colonocytes.

Animals↗