Search PubMed⌕ Search

Biomedical subjects

J G Morelli

Publications and source records attributed to J G Morelli.

At least 73 records · Page 4Linked to original sources

Leukotriene B4-induced human melanocyte pigmentation and leukotriene C4-induced human melanocyte growth are inhibited by different isoquinolinesulfonamides.

Leukotriene C4 (LTC4) is known to be a potent mitogen for cultured human neonatal melanocytes. We now demonstrate that leukotriene B4 (LTB4) can induce pigmentation in cultured human neonatal melanocytes in a dose-dependent fashion. The LTC4-induced mitogenesis is blocked by the cyclic nucleotide-dependent kinase inhibitor N-[2-(methyl-amino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H8). The LTB4-induced pigmentation is blocked by the protein kinase C inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H7). We propose that LTB4-induced pigmentation and LTC4-induced mitogenesis are important in vivo signals. Their different effects in our culture system are blocked by different protein kinase inhibitors.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Leukotriene C4 and TGF-alpha are stimulators of human melanocyte migration in vitro.

Human vitiligo is a disease of melanocyte destruction that leads to areas of depigmentation in the skin. The major form of treatment for vitiligo is photochemotherapy using psoralens and UVA radiation (PUVA), which induces the slow migration of pigment cells from hair follicles and normal skin into the depigmented areas. Our hypothesis is that immune cytokines and inflammatory mediators released as a result of the photochemotherapy are signals for melanocyte migration. We have developed an in vitro assay that quantitates the movement of individual cultured melanocytes over a 72-h period using time-lapse photography. Using this assay we found that both LTC4 and TGF-alpha were stimulators of melanocyte migration in vitro. The LTC4 effect was greater and lasted for the entire 72-h experimental period, whereas the TGF-alpha effect was significant only during the first 24 h of the experiment.

Cell Movement↗

Treatment of ulcerated hemangiomas with the pulsed tunable dye laser.

Hemangiomas are the most common tumor of infancy and are characterized by rapid growth during the first 6 months of life. During the rapid growth phase, approximately 5% to 10% of the hemangiomas ulcerate. Ulcerated lesions are painful, may bleed, and are at risk for bacterial infection. Previous therapy has included daily local wound care, topical antibiotics, and local and systemic steroids. We treated nine infants (eight female and one male) with ulcerated hemangiomas by means of a vascular-specific (585-nm) pulsed (450-microsecond) tunable dye laser. Eight of the nine patients had a single ulceration, whereas one patient had two ulcerations within a large hemangioma. Six of the ulcerations healed with a single laser treatment. One ulceration required two treatments to heal, and the remaining two required three treatments. Pain was subjectively decreased within 2 to 3 days in all patients after a single treatment. The pulsed tunable dye laser should be considered in the treatment of all ulcerated hemangiomas.

Evaluation Studies as Topic↗

Location of port-wine stains and the likelihood of ophthalmic and/or central nervous system complications.

Of 310 patients with port-wine stains, 68% had more than one dermatome involved; 85% had unilateral and 15% had a bilateral distribution of their port-wine stain. At the time of examination, 8% of all patients with trigeminal port-wine stains had evidence of eye and/or central nervous system (CNS) involvement. Extensive involvement, with port-wine stain over the trunk and extremities as well as the head and neck, was observed in 12%. Patients who did not have port-wine stains on the areas served by branches V1 and V2 of the trigeminal nerve had no signs or symptoms of eye and/or CNS involvement. Port-wine stains of the eyelids, bilateral distribution of the birthmark, and unilateral port-wine stains involving all three branches of the trigeminal nerve were associated with a significantly higher likelihood of having eye and/or CNS complications. Twenty-four percent of those with bilateral trigeminal nerve port-wine stains had eye and/or CNS involvement compared with 6% of those with unilateral lesions. All those who had eye and/or CNS complications had port-wine stain involvement of the eyelids; in 91% both upper and lower eyelids were involved, whereas in 9% only the lower eyelid was involved. None of those with upper eyelid port-wine stains alone had eye and/or CNS complications. In addition, 3 (75%) of the 4 subjects with seizures alone had bilateral port-wine stain involvement. A third group, these with unilateral V1, V2, and V3 port-wine stains, had eye and/or CNS complications in 3 (19%) of 16 subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

Metabolism of exogenous leukotrienes by cultured human keratinocytes.

Leukotrienes are involved in diseases associated with a neutrophilic infiltrate. The role of human keratinocytes in the metabolism and inactivation of leukotrienes has not been thoroughly examined. We added exogenous radioactive leukotrienes to cultured human keratinocytes and evaluated the metabolic products using high-performance liquid chromatography. Over a 24-h period, unstimulated cultured keratinocytes convert leukotriene B4 to unidentified polar molecules. Leukotriene C4 is converted to a leukotriene D4/leukotriene E4-like product. Cultured human keratinocytes have the ability to metabolize leukotrienes and thus the keratinocyte may play a major role in the in vivo metabolism of leukotrienes produced during inflammatory dermatoses.

Binding Sites↗

Leukotrienes C4 and D4 as potent mitogens for cultured human neonatal melanocytes.

Arachidonic acid and its metabolites (eicosanoids) are membrane-derived inflammatory mediators with a diverse set of biologic properties affecting numerous cells and organ systems, including the skin. They have been implicated in the pathogenesis of inflammatory skin disease and post-inflammatory hyperpigmentation. We have studied the ability of arachidonic acid, prostaglandin D2, prostaglandin E2, leukotriene B4, leukotriene C4, leukotriene D4, and leukotriene E4 to enhance the growth of cultured human melanocytes. Of these compounds, only leukotriene C4 and leukotriene D4 were capable of stimulating melanocyte proliferation. In addition, cultured melanocytes metabolized leukotriene C4 to leukotriene E4 with greater than 60% conversion in less than three hours. Melanocytes grown on suboptimal media (doubling time 12-20 days) respond in a dose-dependent fashion to leukotriene C4, with a significant difference from control noted at 28 days with a concentration of LTC4 of 30 nM and a doubling time of 5-8 days. We feel that leukotriene C4 and D4 could play an important role in post-inflammatory melanocyte hyperplasia.

Cells, Cultured↗

Ultrastructural changes in red blood cells following pulsed irradiation in vitro.

The careful choice of a combination of laser parameters such as wavelength, pulse duration, and dose has provided a means for confining laser energy to specific targets within tissue such as oxyhemoglobin within the cutaneous microvasculature. In the process of achieving such vascular selectivity, certain ultrastructural changes in red blood cell (RBC) cytoplasm have been observed, such as the generation of intracytoplasmic electron-lucent spherical structures. These structures, ranging in size from 80 to 1000A, were seen in RBCs exposed to laser doses at and above threshold, and appeared to represent a morphologically novel form of highly-specific tissue injury. This in vitro study using RBC in phosphate buffered saline (PBS) was undertaken to better understand the mechanism(s) that could have been responsible for these unique morphologic changes. We conclude that the intracytoplasmic electron-lucent spherical structures seen within RBCs were heat-fixed molds formed around vaporized water bubbles and were not produced by the release of oxygen from the oxyhemoglobin moiety during 577-nm laser irradiation.

Erythrocytes↗

193 nm excimer laser selective ablation of in vivo guinea pig epidermis.

We have previously shown that 193 nm excimer laser irradiation cleanly and effectively ablates avascular tissue with minimal thermal damage to surrounding adjacent structures. In this study, the 193 nm excimer laser is used to remove guinea pig epidermis in vivo. The epidermis can be totally ablated with thermal damage extending only superficially into the dermis. Reepitheliazation of the ablated area takes place in 1 week or less. This technique may be applicable to the removal of benign epidermal lesions.

Animals↗

Soaps and shampoos in pediatric practice.

Cleansing of the skin and hair is part of the daily routine of all neonates, infants, toddlers, children, and adolescents. Numerous soap and shampoo products are available to the consumer. The pediatrician is often asked to comment on the safety and efficacy of these products. Little information is available to help the pediatrician make a rational decision. The list of ingredients on the package are seldom useful and can be confusing. The theoretical and practical considerations leading to the addition of the major constituents of soaps and shampoos are reviewed and guidelines for the use of soaps and shampoos under normal circumstances and in a few selected conditions are suggested.

Baths↗

Tunable dye laser (577 nm) treatment of port wine stains.

Despite steady improvement in the laser treatment of port wine stains (PWS), hypertrophic scarring remains a serious side-effect in approximately 10% of patients. The tunable dye laser (577 nm) has been shown to cause selective vascular destruction in normal and PWS skin. We have treated ten patients using a tunable dye laser (577 nm, 300 mu sec) resulting in clearing of the PWS without any evidence of hypertrophic scarring. Treatment requires no anesthesia or wound care, and there were no postoperative infections.

Adolescent↗

Lasers in dermatology: a selective historical review.

Lasers have been used in dermatology for over 20 years. Multiple lesions including port wine stains, decorative tattoos, malignant tumors, and keloids have been treated with various lasers. Initial therapy exploited the laser property of spatial confinement of an extremely high energy density to create a localized thermal effect. With increased understanding of laser technology, skin optics, and laser-tissue interactions, other laser properties such as monochromaticity and pulsewidth variability have been exploited to even further confine damage to pathologic tissue while maximally sparing surrounding normal tissue. This increased knowledge has led to a vast improvement in the results of dermatologic laser therapy. Despite this, laser therapy still remains a surgical art, with wound healing playing a large part in the final outcome.

Basal Cell Carcinoma↗

Childhood immunobullous disease following a second organ transplant.

Immunobullous diseases are quite unusual in children. We report two children who developed immunobullous disease shortly after a second solid organ transplantation. One child had IgA pemphigus vegetans, the other bullous pemphigoid. We hypothesize that the repeat organ transplantation served as a "booster" immunization for autoantibody production. Both children developed their immunobullous condition while being treated with immunosuppressive drugs that are used to treat immunobullous disorders.

Adolescent↗

Childhood pernio and cryoproteins.

Childhood pernio is an uncommon condition described mainly through isolated case reports. We examined the cutaneous spectrum, clinical associations, presence of cryoproteins, and evolution of the condition in children, and performed a retrospective case series evaluation of children with pernio seen at a single ambulatory care university center over a 10-year period. Cases were drawn from a population of 3.2 million. Follow-up was at least 3 years. We found four boys and four girls with pernio. Distribution of skin lesions was on the fingers, toes, and ears. Four children had cryoglobulins or cold agglutinins, two had a positive rheumatoid factor, and none had a positive ANA or ANA profile. All eight cleared within 3 months and did not recur over at least a 3-year period. We concluded that childhood pernio is uncommon and may be associated with the presence of cryoproteins.

Adolescent↗

Experience with UVB phototherapy in children.

Twenty children age 14 months to 12 years with photoresponsive dermatoses were treated with ultraviolet B (UVB) phototherapy over four years. Ten children had psoriasis, five had pityriasis lichenoids, and five had atopic dermatitis. All received short courses (average 34 treatments) of phototherapy with either no maintenance or short maintenance. Treatment was effective and well tolerated in most patients, and no serious side effects were seen. Patients with psoriasis and pityriasis lichenoides cleared completely. No patient with atopic dermatitis cleared completely, but all were moderately improved, with reduction of the extent of eczema and decreased pruritus. It appears that UVB phototherapy is a valuable and safe therapeutic option for selected children who do not respond to other treatments.

Child↗