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Biomedical subjects

J G Morelli

Publications and source records attributed to J G Morelli.

At least 37 records · Page 2Linked to original sources

Herpes simplex virus-associated erythema multiforme in prepubertal children.

OBJECTIVE: To examine clinical associations, evolution of the condition, and response to treatment of erythema multiforme (EM) in prepubertal children. DESIGN: A retrospective case series evaluation of children younger than 13 years with EM. SETTING: Ambulatory care university hospital. PATIENTS: Referral patients from pediatricians serving a population of 3.2 million. INTERVENTIONS: Results of treatment of each EM episode with topical acyclovir or oral acyclovir at a dose of 25 mg/kg per day and 6-month prophylaxis with oral acyclovir at a dose of 20 mg/kg per day were evaluated. OUTCOMES: Age at EM onset, preceding illness, and number and duration of episodes during a 3-year period were recorded. RESULTS: Twelve children (7 boys and 5 girls) in whom herpes simplex virus (HSV)-associated EM developed were evaluated. Preceding lesions were herpes labialis in 8 children and herpes facialis in 2 children. Two children had no obvious HSV lesion. The mean age at onset of disease was 8.1 years, and the mean time from the preceding HSV to the onset of skin lesions was 3.9 days (range, 0-11 days). Episodes of EM lasted a mean of 10.6 days. In 9 children, the EM was recurrent, with a mean of 2.6 episodes per year. All 12 children, including those with negative viral cultures for HSV or no HSV history had HSV detected in their target lesions by polymerase chain reaction amplification of DNA obtained from skin biopsy specimens. Six of 12 children were treated with oral acyclovir at a dose of 25 mg/kg per day for 1 or more individual episodes, without reduction in the episode. Three children underwent 6-month prophylaxis with oral acyclovir at a dose of 20 mg/kg per day and remained disease free during treatment. After discontinuation of the prophylactic treatment with acyclovir, 1 child relapsed at 4 months. The other 2 children had no further episodes during a 3-year period. CONCLUSIONS: The HSV-associated EM is a recurrent disease that can be precipitated by sun exposure and does not progress to Stevens-Johnson syndrome. Childhood HSV-associated EM may be unresponsive to treatment with oral steroids or oral or topical acyclovir. Frequent recurrences of EM may be abrogated by prophylactic treatment with acyclovir.

Acyclovir↗

Target lesions on the lips: childhood herpes simplex associated with erythema multiforme mimics Stevens-Johnson syndrome.

Erythema multiforme and Stevens-Johnson syndrome are both characterized by areas of epithelial necrosis. An important clinical feature that distinguishes the two is the extensive mucosal necrosis in Stevens-Johnson syndrome but not in erythema multiforme. Because significant and serious complications may develop with Stevens-Johnson syndrome and not with erythema multiforme, it is important to differentiate between the conditions. We describe three boys with herpes simplex virus-associated erythema multiforme who had severe necrosis of the lips develop and were initially diagnosed with Stevens-Johnson syndrome. The lip lesions were large target lesions of erythema multiforme rather than the extensive necrosis seen in Stevens-Johnson syndrome and all three had a benign course.

Child↗

Identification of sn-2 acetyl glycerophosphocholines in human keratinocytes.

Evidence is accumulating suggesting that platelet-activating factor plays a role in inflammatory dermatoses. Mass spectrometric methods were used to examine the molecular species of sn-2 acetyl glycerophosphocholines (GPC) synthesized by primary cultures of human neonatal foreskin-derived keratinocytes. Ionophore-stimulated keratinocytes synthesize both 1-alkyl and 1-acyl sn-2 acetyl-GPC, and the relative amounts were as follows: hexadecyl > palmitoyl > octadecyl > stearoyl at the sn-1 position. PAF synthesis in the keratinocyte-derived cell line HaCaT was inhibited by dexamethasone, suggesting that the anti-inflammatory effects of glucocorticosteroids in inflammatory dermatoses might be in part related to the inhibition of the synthesis of mediators such as PAF.

Adrenal Cortex Hormones↗

Treatment of pyogenic granuloma in children with the flashlamp-pumped pulsed dye laser.

OBJECTIVE: Pyogenic granuloma is a common, acquired, vascular tumor of the skin in children, often ulcerates or bleeds, and is commonly localized to the face. The treatment of choice has been surgical removal, either by excision or shave, followed by electrocautery. The site, young age of the patient, and the inherent nature of surgical removal or electrocautery often make this procedure a traumatic experience. Also, surgical treatment usually leads to permanent scarring. Owing to the pulsed dye laser's ability to cause selective destruction of superficial capillary-sized cutaneous blood vessels, its ease of operation, and its lack of scarring, we evaluated its use in the treatment of pyogenic granuloma in children. METHODS: Twenty-two children with solitary pyogenic granulomas were treated with a vascular-specific (585 nm), pulsed (450 microseconds) dye laser using a 5-mm spot size with a laser energy of 6 to 7 J/cm2 without anesthesia. Retreatments were administered every 2 weeks if necessary until the lesion cleared. Posttreatment care consisted of twice-a-day application of bacitracin ointment. RESULTS: In 20 patients (91%), laser treatment was successful. Five patients (25%) required one treatment for resolution, eight patients (40%) required two treatments, and six patients (30%) required three treatments for clearing. One patient required six treatments before the lesion resolved. There was no correlation with the duration, or site of the lesion, with respect to the number of laser treatments required. Lesions in all 20 children healed without scarring and with excellent cosmetic results. In two patients (9%), laser treatment failed in that there was no response to the initial laser treatment on follow-up 2 weeks later. Both had large pyogenic granulomas (1 cm and .5 cm in diameter, respectively) which were elevated over .5 cm above the surface of the skin. These lesions were surgically removed. None of the patients had a recurrence during the follow-up period of 6 months to 3 years. CONCLUSION: Pulsed dye lasers are effective and safe for the treatment of small pyogenic granulomas in children and should be considered a treatment option.

Adolescent↗

Lesion size is a factor for determining the rate of port-wine stain clearing following pulsed dye laser treatment in adults.

Seventy-four adult patients with facial, truncal, and extremity port-wine stains (PWS) were treated with the flashlamp-pumped pulsed dye laser (PDL) with laser output ranging from 6.0 to 7.5 J/cm2. Response to treatment was analyzed by comparing the area of involvement following each treatment with the area of involvement measured in the first treatment session. All the PWS responded with 25 to 90 percent lightening, and 85.1 percent of patients achieved 25 percent clearing. However, only 36.5 percent achieved 50 percent clearing, and none of the patients achieved 100 percent clearing. None of four patients with PWS greater than 100 cm2 achieved 50 percent clearing following a mean of 17.2 +/- 5.7 treatments. These data emphasize the importance of objectively documenting clinical response to PDL treatment of PWS. Adult patients need to be made aware that complete clearing may not be obtainable by PDL treatment alone. This is especially important for adult patients with PWS larger than 100 cm2.

Adult↗

Platelet-activating factor biosynthesis induced by various stimuli in human HaCaT keratinocytes.

Platelet-activating factor (PAF) is a potent inflammatory mediator that is thought to play a role in cutaneous inflammation. These studies used mass spectrometry to examine the molecular species of PAF precursor glycerophosphocholine lipids (GPC) as well as the biosynthesis of PAF and other sn-2 acetyl-GPC in a human keratinocyte-derived cell line (HaCaT keratinocytes). Approximately 28% of HaCaT keratinocyte GPC consisted of 1-alkyl species, and the relative amounts of the sn-1 alkyl constituents of the PAF precursor 1-alkyl-2-acyl-GPC were as follows: hexadecyl > octadecenyl > octadecyl. Ionophore (A23187)-stimulated HaCaT keratinocytes synthesized both PAF (1-hexadecyl, 1-octadecenyl, and 1-octadecyl species) and less potent 1-acyl analogs (1-palmitoyl, 1-oleoyl, and 1-stearoyl species). PAF production was rapid and maximal by 10 min. The major species of sn-2acetyl-GPC at 2.5 min were 1-hexadecyl-2-acetyl-GPC (2.2 ng/10(6) cells) and 1-palmitoyl-2-acetyl-GPC (2.4 ng/10(6) cells). HaCaT keratinocytes also synthesized PAF and 1-acyl PAF analogs when stimulated with the peptide growth factor endothelin-1 and the nonhydrolyzable PAF receptor agonist carbamyl-PAF. Both 1-hexadecyl-2- acetyl-GPC and 1-palmitoyl-2-acetyl-GPC stimulated intracellular calcium mobilization in HaCaT cells, indicating that these sn-2 acetyl-GPC act in autocrine fashion. These studies revealed that the human keratinocyte-derived cell line HaCaT can synthesize significant amounts of PAF and 1-acyl analogs in vitro from both nonspecific (A23187) and specific (endothelin-1, carbamyl-PAF) stimulation, suggesting a role for this inflammatory lipid mediator in keratinocyte pathophysiology.

Calcimycin↗

DOPA-negative melanocytes in the outer root sheath of human hair follicles express premelanosomal antigens but not a melanosomal antigen or the melanosome-associated glycoproteins tyrosinase, TRP-1, and TRP-2.

It is believed that DOPA-negative melanocytes in the outer root sheath of the human hair follicle are activated, become identifiable by DOPA staining, and migrate into the epidermis during the repigmenting phase of vitiligo. These cells are difficult to identify, however, and otherwise have not been characterized. These cells are readily identified by immunofluorescence, immunohistochemistry, and immunoelectronmicroscopy using the antibodies NKI/beteb and A4F11, which recognize premelanosome-related antigens. The majority of the outer root sheath melanocytes were found in the mid to the upper portion of the hair follicle. Double staining revealed that these cells were distinct from HLA-DR-bearing dendritic cells. Further immunohistochemical investigation using alpha-PEP-7, alpha-PEP-1, or TMH-1 and alpha-PEP-8 antibodies revealed that outer root sheath melanocytes cannot be identified by antibodies to tyrosinase, TRP-1, or TRP-2, respectively. These cells also did not react with HMB45 antibody, which recognizes a melanosome-associated cytoplasmic antigen. We believe that the inactive outer root sheath melanocytes contain some of the early structural proteins but not any of the enzymatic proteins necessary for melanogenesis. Therefore, activation is the process whereby outer root sheath melanocytes acquire all of the structural and enzymatic proteins necessary for melanogenesis.

Adult↗

Expression of E and P-cadherin by melanoma cells decreases in progressive melanomas and following ultraviolet radiation.

The purpose of our study was to determine whether the degree of E- and P-cadherin expression in melanomas correlates with the invasive behavior of the clinical lesions from which the cell lines were derived. Cadherins comprise a family of calcium-dependent cellular adhesion molecules expressed on most cell types that form solid tissues. In the human epidermis, melanocyte cadherin expression may function to maintain the integrity of the epidermal-melanin unit. Employing both immunofluorescence microscopy and fluorescence-activated cell sorter analysis, we localized and quantitated E- and P-cadherin expression on melanoma cell lines derived from primary or metastatic lesions using the monoclonal antibodies HECD-1 and NNC-CAD-299, respectively. Human epidermal melanocytes isolated from neonatal foreskin were evaluated by similar techniques and served as a biologic control. Melanoma cell lines were isolated from primary or metastatic lesions of patients described as having "early," "intermediate," or "advanced disease." Melanoma E- and P-cadherin immunofluorescence, as quantified by fluorescence-activated cell sorter, varied inversely with disease progression. Selected log mean ratios of E-cadherin fluorescence, as compared to human epidermal melanocytes (arbitrarily = 1), ranged from 1.04 in the WM 35 melanoma cell line (low invasive potential) to 0.1 and 0.02 in the WM 983A and 1361A melanoma cell lines (derived from primary lesions with metastases), respectively. Although values for P-cadherin fluorescence were less, the trend of decreasing cadherin amounts with more advanced disease was observed. Melanoma cells appear to express E- and P-cadherin levels inversely related to disease progression. Ultraviolet radiation significantly decreased E- and P-cadherin expression in the human epidermal melanocytes and P-cadherin expression in the WM 35 melanoma cell line (p < 0.05). Although not statistically significant, E-cadherin expression in the WM 35 melanoma cell line decreased substantially. Thus, ultraviolet radiation may have a direct effect on human epidermal melanocytes and melanoma cell attachment through cadherins within the epidermis or tumor nodules.

Cadherins↗

Effective elimination of fibroblasts in cultures of melanocytes by lowering calcium concentration in TPA depleted medium following geneticin treatment.

Melanocytes grow well in culture media supplemented with phorbol ester. However, phorbol ester is metabolically stable and has prolonged effects on multiple cellular responses. Different groups have reported that they could cultivate melanocytes without phorbol ester. However, in medium without phorbol esters contaminating fibroblasts are often difficult to eliminate. We have developed an improved method of eliminating fibroblasts using geneticin in serum free medium with bFGF, endothelin-1 and no phorbol ester. Treatment with a low concentration of geneticin effectively eliminated contaminating fibroblasts and was not harmful to melanocytes if geneticin was added initially in a high calcium media (2 mM) followed by a change to a low (0.09 mM) calcium media immediately after removal of the geneticin. With this technique we could easily establish pure melanocyte culture. This culture method will provide a useful tool for studies on melanocyte cellular response without the influence of phorbol ester.

Anti-Bacterial Agents↗

Focal facial dermal dysplasia: report of a case with associated cardiac defects.

Focal facial dermal dysplasia is characterized by congenital scar-like depressions on both temples and a wide spectrum of associated facial abnormalities. We report a 2-month-old white boy who presented with bitemporal defects, laterally deficient eyebrows, absent lower eyelashes, periorbital puffiness, a bulbous nasal tip with prominent sebaceous hyperplasia, and down-turned corners of the mouth. In addition, he had tetralogy of Fallot, an association which previously has not been described.

Abnormalities, Multiple↗

Initial lesion size as a predictive factor in determining the response of port-wine stains in children treated with the pulsed dye laser.

OBJECTIVE: To evaluate the response of facial port-wine stains in children to pulsed (450 microseconds) dye (577- or 585-nm) laser treatment based on the age of the patient and the size of the port-wine stain at the initiation of treatments. DESIGN: Case series. SETTING: Outpatient dermatology clinic at the University of Colorado School of Medicine, Denver. PATIENTS: A consecutive sample of 83 children who had facial port-wine stains that were treated in their entirety at each visit. INTERVENTION: Patients were treated with a pulsed (450 microseconds) dye (577- and 585-nm) laser. MAIN OUTCOME MEASURE: Decrease in size of the port-wine stain. RESULTS: Overall 18 (22%) of the 85 patients responded with complete clearing of their port-wine stains. The port-wine stains in 32% (7/22) of the patients who began treatment before 1 year of age responded with complete clearing of their port-wine stains compared with 18% (11/61) in older patients (P < .01). Fifteen (32%) of 47 patients with port-wine stains smaller than 20 cm2 at initial evaluation were totally cleared vs three (8%) of the 36 patients with port-wine stains larger than 20 cm2 (P < .05). This size effect is apparent at all ages. CONCLUSION: When considering treatment for facial port-wine stains with pulsed dye lasers, it is important to consider not only the age of the child at the beginning of treatments, but also the initial size of the lesion.

Adolescent↗

Atopic dermatitis: is it an allergic disease?

For many years controversy has surrounded the relation between allergy and atopic dermatitis. We critically review the evidence for the contribution of allergy, or IgE-mediated hypersensitivity reactions, to the pathogenesis of this disease. We conclude that, at present, there is scant evidence that allergy is central to the development of atopic dermatitis, although it may be an aggravating factor in a few patients. Hence there is little rationale for the routine use of allergy testing or dietary and environmental manipulation in the management of this disease.

Allergens↗

Identification of functional platelet-activating factor receptors on human keratinocytes.

Platelet-activating factor (PAF) is a potent inflammatory mediator that has been shown to be produced by human keratinocytes and is thought to play a role in cutaneous inflammation. Immunofluorescence and radioligand binding studies were used to characterize PAF receptors (PAF-R) on human keratinocytes and the human epidermoid cell lines A-431 and HaCaT. Indirect immunofluorescence studies demonstrated anti-PAF-R staining of primary cultures of human keratinocytes, A-431 cells, and HaCaT cells. Primary cultures of human fibroblasts and the melanoma cell line SK-30 failed to show immunostaining above that seen with control antiserum. With indirect immunofluorescence studies of sections of normal human skin, a granular anti-PAF-R staining pattern was noted on the keratinocyte cell membranes. A-431 cells readily metabolized PAF by deacetylation-reacylation at 37 degrees C, but not at 4 degrees C. Binding studies on crude membrane preparations of A-431 cells conducted at 4 degrees C demonstrated specific binding that reached saturation by 120 min. Scatchard analysis of PAF binding data revealed a single class of high-affinity (KD = 6.3 +/- 0.3 nM) PAF binding sites. The immunofluorescence and radioligand binding sites were shown to be functional PAF-Rs, as 10 pM to 1 microM PAF increased intracellular calcium in primary cultures of human keratinocytes, A-431 cells, and HaCaT cells, whereas PAF treatment of primary cultures of human fibroblasts or the melanoma cell line SK-30 did not result in changes in the intracellular calcium concentration. The structurally dissimilar PAF-R antagonists CV-6209, Ro19-3704, and alprazolam all inhibited the PAF-induced calcium changes in A-431 cells. The CV-6209 inhibition was seen at doses that competed with the PAF binding to these cells. These studies provide the first evidence for the presence of a functional PAF-R expressed on human keratinocytes, suggesting that this lipid mediator may play an important role in normal keratinocytes or in inflammatory dermatology.

Calcium↗

Melanocyte mitogens induce both melanocyte chemokinesis and chemotaxis.

It is believed that during repigmentation of vitiligo, inactive melanocytes in the outer root sheath of the hair follicle become activated, proliferate, and migrate into the depigmented skin. However, the mechanisms controlling melanocyte migration remain to be elucidated. In this study, we investigated the effects of well-described melanocyte growth factors on melanocyte migration. Using time-lapse photography, we demonstrated that melanocyte chemokinetic movement was induced by basic fibroblast growth factor, stem cell factor, and endothelin-1, with the greatest effect noted using 100 nM endothelin-1. Similar results were reported previously with leukotriene C4. When surrounded by these stimuli, melanocytes moved in a random, nonlinear fashion and showed no desensitization at the concentrations studied. In Boyden chamber checkerboard analysis, basic fibroblast growth factor, leukotriene C4 and endothelin-1 were chemotactic. They produced directional migration and showed desensitization at higher concentrations. The greatest effect again was seen with 100 nM endothelin-1. Stem cell factor showed no effect in this assay system at the concentrations tested. The four melanocyte mitogens--leukotriene C4, endothelin-1, basic fibroblast growth factor, and stem cell factor--stimulate melanocyte migration, and this migration may be either chemokinetic (activated random movement) or chemotactic (requiring a gradient, directional, and showing desensitization), depending on the conditions used. We believe that these factors may be effective in stimulating vitiligo repigmentation by inducing proliferation and migration of hair-follicle outer-root-sheath melanocytes into the depigmented epidermis.

Cell Adhesion Molecules↗