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Biomedical subjects

B A Gilchrest

Publications and source records attributed to B A Gilchrest.

At least 181 records · Page 10Linked to original sources
PubMed1983

Increased concentrations of arachidonic acid, prostaglandins E2, D2, and 6-oxo-F1 alpha, and histamine in human skin following UVA irradiation.

The buttock skin of clinically normal human subjects was subjected to approximately 2.5 minimal erythema doses of ultraviolet A irradiation. Deep red erythema developed during irradiation, faded slightly within the next few hours, increased to maximum intensity between 9-15 h, and decreased gradually thereafter although still persisting strongly at 48 h. Suction blister exudates were obtained at 0, 5, 9, 15, 24, and 48 h after irradiation as well as suction blister exudates from a contralateral control site and assayed for arachidonic acid, prostaglandins D2 and E2, and the prostacyclin breakdown product 6-oxo-prostaglandin F1 alpha by gas chromatography-mass spectrometry, and for histamine by radioenzyme assay. Increased concentrations of arachidonic acid and prostaglandins D2, E2, and 6-oxo-prostaglandin F1 alpha were found maximally between 5-9 h after irradiation, preceding the phase of maximal erythema. Elevations of histamine concentration occurred 9-15 h after irradiation, preceding and coinciding with the phase of maximal erythema. At 24 h, still at the height of the erythemal response, all values had returned to near control levels. Hence increased concentrations of arachidonic acid and its products from the cyclooxygenase pathway, and of histamine, accompany the early stages up to 24 h. A causal role in production of the erythema seems likely for these substances although other mediators are almost certainly involved.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

In vitro assessment of keratinocyte aging.

In vitro aging models are based on the observation that normal cells in culture have a finite lifespan and eventually cease to proliferate under conditions that initially support excellent growth. Recent assessment of the aging process in keratinocytes, made possible by improved tissue-culture techniques, have confirmed prior findings with fetal and adult fibroblasts and have permitted investigation into the mechanism of in vitro senescence. Early-passage newborn human keratinocytes maintained in a serum-free system were found to proliferate more rapidly than early-passage adult keratinocytes maintained under identical conditions, and they were also found to have far steeper dose-response curves for a potent hypothalamus-derived mitogen keratinocyte growth factor (KGF), as well as for KGF/EGF in combination, with a more than 200-fold increase in cell number, total protein, and colony size over the tested range of concentrations, as opposed to a less than 75-fold increase for adult keratinocytes in these parameters. These results support the hypothesis that the age-associated decrease for keratinocyte proliferation in vitro may be due to progressive loss of mitogenic responsiveness. Unrecognized changes in proliferative rate and growth-factor requirements related to age of the tissue donor may complicate interpretation of studies addressing other aspects of keratinocyte biology.

Adult↗
PubMed1983

In vivo spectrophotometric evaluation of normal, lesional, and laser-treated skin in patients with port-wine stains.

The influence of patient age and argon laser therapy on port-wine stains (PWS) was studied quantitatively in 16 patients aged 15-64 years using a spectrophotometer and computer graphics/statistics program. Normalized reflectance curves revealed a 10-20% decrease with age in the reflectance of normal skin from 400 nm to 650 nm, with an even more pronounced reflectance decrease in the region of peak deoxyhemoglobin absorption at approximately 555 nm. In each patient, PWS reflectance was less than that in the normal skin, as expected, and the average discrepancy increased with age from approximately 25% to 50%, with further reduction at 555 nm. The data suggest that with advancing age, both normal skin and PWS have a greater total hemoglobin content and an increased proportion of deoxyhemoglobin, consistent with increasing vascular dilation and tortuosity; and that the age-associated changes in PWS are an exaggeration of those in normal skin. Laser-treated PWS in both young and old patients had reflectance curves indistinguishable from those of untreated PWS in young patients. This implies, contrary to published clinical impressions, that in the absence of scarring the results of argon laser therapy are the same in young and old patients, but that only older patients experience a significant color shift in the lesion.

Adolescent↗
PubMed1983

Chronologic and actinically induced aging in human facial skin.

Clinical and histologic stigmata of aging are much more prominent in habitually sun-exposed skin than in sun-protected skin, but other possible manifestations of actinically induced aging are almost unexplored. We have examined the interrelation of chronologic and actinic aging using paired preauricular (sun-exposed) and postauricular (sun-protected) skin specimens. Keratinocyte cultures derived from sun-exposed skin consistently had a shorter in vitro lifespan but increased plating efficiency compared with cultures derived from adjacent sun-protected skin of the same individual, confirming a previous study of different paired body sites. Electron microscopic histologic sections revealed focal abnormalities of keratinocyte proliferation and alignment in vitro especially in those cultures derived from sun-exposed skin and decreased intercellular contact in stratified colonies at late passage, regardless of donor site. One-micron histologic sections of the original biopsy specimens revealed no striking site-related keratinocyte alterations, but sun-exposed specimens had fewer epidermal Langerhans cells (p less than 0.001), averaging approximately 50 percent the number in sun-protected skin, a possible exaggeration of the previously reported age-associated decrease in this cell population. These data suggest that sun exposure indeed accelerates aging by several criteria and that, regardless of mechanism, environmental factors may adversely affect the appearance and function of aging skin in ways amenable to experimental quantitation.

Age Factors↗
PubMed1982

Pruritus: pathogenesis, therapy, and significance in systemic disease states.

Pruritus is a cutaneous sensation sharing neural receptors and pathways with pain but is characterized by its own precipitants, potentiators, and range of severity. Among patients with generalized pruritus, the prevalence of systemic disease has been reported as 10% to 50%, with renal, hepatic, hematopoietic, or endocrine causes most commonly identified. Malignant neoplasms, neurologic disorders, certain drugs, or advanced age also may be responsible. Although the pathogenesis of pruritus is unknown, clinically AG event potential mediators have been investigated in several settings. Therapy often fails when the underlying disorder cannot be corrected, but por pruritus associated with chronic renal failure or hepatic cholestasis, specific and usually effective treatments exist.

Cholestasis↗
PubMed1982

Attachment and growth of human keratinocytes in a serum-free environment.

Using a serum-free system, we have investigated the influence of human fibronectin (HFN) and selected growth factors (GF) on the attachment and growth of normal human keratinocytes in vitro. Single-cell suspensions of keratinocytes from near-confluent primary plates, plated on 5-10 microgram/cm2 HFN, showed approximately 30-40% attachment after 2-24 hours of incubation at 37 degrees C, compared with 4-6% attachment on uncoated platic plates. Percentage of attached cells was independent of seed density, tissue donor age, in vitro culture age, or medium composition, while subsequent cellular proliferation was strongly dependent on these factors. Keratinocytes grown on an adequate HFN matrix in a previously described hormone-supplemented medium (Maciag et al., 1981a) achieved four to eight population doubling over 7-12 days at densities greater than or equal to 104 cell/cm2. Removal of most GF individually from the medium had little or no effect on growth, while removal of epidermal growth factor (EGF) alone reduced growth by 30-35% and removal of bovine brain extract (BE) alone reduced growth by approximately 90%. Conversely, EGF alone in basal medium supported approximately 10% control growth, BE alone supported 30-40% control growth, and the combination of EGF and BE approximately 70%. In addition to its major effect on proliferation in this system, BE was necessary to preserve normal keratinocyte morphology and protein production. These findings expand earlier observations that HFN facilitates keratinocyte attachment in vitro and that a brain-derived extract can exert a major positive influence on cultured keratinocytes.

Cell Adhesion↗
PubMed1982

Chilling port wine stains improves the response to argon laser therapy.

Twenty-three patients with facial port wine stains were studied to determine whether chilling lesional skin at the time of treatment could improve the outcome of argon laser therapy and whether this effect could be attributed to increased hemoglobin content of chilled sites, as hypothesized on clinical grounds. Each patient was biopsied in two representative and clinically identical sites, once at room temperature and once immediately after application of ice to the skin surface for 2 to 3 minutes. Two additional identical sites were treated with an argon laser in the same manner. Histologic sections of the port wine stain after application of ice tended to have a higher percentage of erythrocyte-filled vessels, but the effect of chilling on the dermal vasculature varied greatly among patients and was not statistically significant. In contrast, chilling of lesional skin prior to laser therapy resulted in a significantly better average outcome (p = 0.0002), with 57 percent of chilled sites superior to the paired room temperature control and none inferior. In nearly all instances of differential response, the site treated at room temperature manifested scarring, while the chilled site did not. Overall, after an average evaluation period of 4.8 months, 65 percent of the patients achieved a good or excellent result in the control site, and 87 percent achieved this result in the chilled site. These data establish the potential benefit of lesional modification prior to argon laser therapy and suggest that in the case of port wine stain chilling, this benefit is due to reduced heat injury of nonvascular elements in the skin.

Adolescent↗
PubMed1982

Effect of chronologic aging and ultraviolet irradiation on Langerhans cells in human epidermis.

The effect of aging on epidermal Langerhans cells (LC) and on their response to a single ultraviolet (UV) exposure was studied in skin biopsy specimens of healthy adults, 4 aged 22-26 yr and 7 aged 62-86 yr. In unirradiated skin, old adults had fewer LC than young adults, 5.8 +/- 1.1 versus 10.0 +/- 0.8 (mean +/- SEM) per 3 mm wide cross-section (p = .015). Following irradiation with 3 times the minimal erythema dose, recognizable LC were absent in all but 2 subjects within 24 hr. However, LC number fell less rapidly in old adults and was almost unchanged at 4 hours (5.8 +/- 1.1 versus 5.0 +/- 1.2), while in young adults LC number decreased from 10.0 +/- 0.8 to 3.3 +/- 1.3 during the same period (p less than .05). Other changes noted in both young and old subjects following irradiation included cytoplasmic vacuolization, frequent apposition of LC to severely damaged keratinocytes, and the finding of LC in the basal layer of the epidermis rather than exclusively suprabasilarly as in control sections. These data demonstrate an age-associated loss of epidermal LC and slowing of LC response to UV irradiation. UV-induced LC changes appear qualitatively similar in young and old adults and include histological evidence of cellular damage, transient association of LC with damaged keratinocytes, and possible migration of LC from the irradiated epidermis within 24 hr.

Adult↗
PubMed1982

Chronologic aging alters the response to ultraviolet-induced inflammation in human skin.

In order to determine the effect of age on the capacity of human skin to mount an inflammatory response, the sunburn reaction was studied quantitatively in 4 subjects aged 22-26 yr and 7 subjects aged 62-86 yr. Buttock skin of each subject was exposed to 3 time his minimal erythema dose, using the Hanovia mercury vapor lamp; 1 micrometer histologic sections and determinations of histamine and prostaglandin E2 (PGE2) from suction blister aspirates were used to monitor the reaction. Clinically, erythema and edema were less (p less than .05) in irradiated skin of the old subjects during the first 24 hr. Nonirradiated skin contained less histamine and PGE2 in old adults (p less than .05), approximately 50% of young adult levels. Histamine levels rose early in the reaction and returned to baseline by 24 hr; 4 hr peak values averaged 9.2 ng/ml in old vs. 18.3 ng/ml in young adults. PGE2 rose more slowly in blister aspirates from old adults (P less than .05), but reached comparable peaks, 6-9 pg/T.V., in both groups at 24 hr. Biopsies of control skin from old adult specimens contained fewer mast cells and venules (P less than .01). At 4 and 24 hr, old specimens revealed fewer sunburn cells and less striking alterations of perivenular mast cells and endothelial cells, but at 72 hr these changes were more prominent than in young adult specimens. The data suggest that with advancing age the sunburn reaction is quantitatively reduced and evolves more slowly following a standardize ultraviolet exposure.

Adult↗
PubMed1982

Age-associated changes in the skin.

Like all organ systems, the skin manifests an age-associated loss of functional capacity and increasing vulnerability to injury and certain disease states. Knowledge of the aging changes in normal skin assists the physician in diagnosis and management of certain dermatoses. Awareness of the important interactions between aging skin and the environment could lead to prevention of many disorders. The burden of skin disease for the elderly is often underestimated. It is psychosocial as well as medical, and although mortality is low, morbidity is high. A rational and caring approach by the general practitioners, family physicians, internists, and geriatricians responsible for this patient population should greatly improve the situation.

Aged↗
PubMed1982

Clinical features of pruritus among patients undergoing maintenance hemodialysis.

Patients undergoing maintenance hemodialysis were asked to complete a questionnaire to define further the nature of uremic pruritus. Of the 237 respondents, 87 (37%) reported "prolonged bothersome itchiness" at the time surveyed, and an additional 97 (41%), not affected at that time, had experienced this problem in the past. Of the 184 patients who reported pruritus in either the past or present, discomfort occurred only during or soon after dialysis in 46 (25%) patients and was most severe at those times in an additional 78 (42%) patients. Topical emollients and orally administered antipruritic agents provided relief in only 33 (18%) and 31 (17%) patients, respectively. These data provide the first statistical basis for certain clinical impressions concerning uremic pruritus and suggest it is not as common among patients who are undergoing dialysis as has been previously implied.

Adult↗
PubMed1981

An endocrine approach to the control of epidermal growth: serum-free cultivation of human keratinocytes.

Human keratinocytes, derived from the skin of newborns and of adults, were grown in the complete absence of serum, in a hormone-supplemented medium on fibronectin-coated cell culture dishes at low seed density. The cell culture medium consisted of Medium 199 containing epidermal growth factor, triiodothyronine, hydrocortisone, Cohn fraction IV, insulin, transferrin, bovine brain extract, and trace elements. Removal of the brain extract from the hormone supplement had a greater negative impact on proliferation of the keratinocyte cultures than did the removal of epidermal growth factor, hydrocortisone, and triiodothyronine or Cohn fraction IV. The growth of keratinocytes in this hormone-supplemented medium suggests that control of keratinocyte growth depends in large part on endocrine stimulation by other body organs, including the brain.

Brain Chemistry↗
PubMed1981

The human sunburn reaction: histologic and biochemical studies.

The ultraviolet-induced erythema reaction was investigated histologically and biochemically in four subjects, utilizing suction blister aspirates, analyzed for histamine and prostaglandin E2 (PGE2), and Epon-embedded 1-mu skin biopsy sections from control skin and from irradiated skin at intervals for 72 hours after exposure to a Hanovia lamp. Major histologic alterations in the epidermis included dyskeratotic and vacuolated keratinocytes (sunburn cells), and disappearance of Langerhans cells. In the dermis the major changes were vascular, involving both the superficial and deep venular plexuses. Endothelial cell enlargement was first apparent within 30 minutes of irradiation, peaked at 24 hours, and persisted throughout the 72-hour study period. Mast cell degranulation and associated perivenular edema were first apparent at 1 hour and striking at the onset of erythema, 3 to 4 hours postirradiation; edema was absent and mast cells were again normal in number and granule content at 24 hours. Histamine levels rose approximately fourfold above control values immediately after the onset of erythema and returned to baseline within 24 hours. PGE2 levels were statistically elevated even before the onset of erythema and reached approximately 150% of the control value at 24 hours. These data provide the first evidence that histamine may mediate the early phase of the human sunburn reaction and increase our understanding of its complex histologic and biochemical sequelae.

Adult↗
PubMed1981

Topical chemotherapy of pigment abnormalities in surgical patients.

Disorders of epidermal pigmentation not amenable to surgical intervention were treated with topical agents in 15 patients. In cases of hypopigmentation, methoxsalen 1% solution was applied prior to photosensitizing ultraviolet light exposures on alternate days for 2 to 6 months. In cases of hyperpigmentation, hydroquinone 4%, retinoic acid 0.05%, and triamcinolone acetonide 0.25% were applied twice daily for 6 weeks. Of three patients with surgically induced depigmentation, all had moderate repigmentation. Of 12 patients with hyperpigmentation, 4 had significant resolution, 5 had partial resolution, and 3 failed to complete the study. Overall, 6 of the 15 patients reported marked satisfaction with their therapy. Mild localized phototoxicity or irritant reactions were the only complications. Topical chemotherapy produced subjective and objective improvement in all patients who completed a therapeutic trial for either hyperpigmentation or hypopigmentation, and in several patients the results were excellent. The safety of these medications and the lack of acceptable alternatives justify their further use in appropriate clinical settings.

Administration, Topical↗
PubMed1981

Premature aging syndromes affecting the skin.

Consideration of the above syndromes from a dermatologic perspective leads to several conclusions: 1) The "normal changes" associated with aging of the skin have been inadequately defined to date. 2) Although all the premature aging syndromes manifest certain features suggestive of accelerated aging, none closely mimics the normal aging process. The distribution, specific character, and developmental sequence of pathologic findings diverge from those of normal aging for most organ systems in each syndrome. Furthermore, in each disorder many of the accepted features of normal aging are lacking. These discrepancies are at least as pronounced in the skin as in the other involved organ systems. 3) Most of the premature aging syndromes are transmitted by autosomal recessive genes, yet have multiple features that are difficult or impossible to attribute to a single defective enzyme or other protein structure. This suggests that the syndromes may be due to errors in the regulation of various metabolic pathways and argues in favor of an explicit genetic program for aging. 4) The frequency and variety of cutaneous abnormalities in these complex syndromes emphasize the integral relationship of the skin to the rest of the body and the potential value of the skin as a tissue source for studies of underlying disease mechanisms. 5) The relatively recent application of tissue culture technology to the study of progeria, Werner syndrome, and the other premature aging syndromes has already yielded considerable data, offering the hope that our understanding of these diseases may increase rapidly in the coming decades.

Adult↗
PubMed1980

Clinical and histological skin changes in chronic renal failure: evidence for a dialysis-resistant, transplant-responsive microangiopathy.

The relation between chronic renal failure and the clinical and histological findings in normal-looking skin was studied in twenty-seven patients with minimum to marked rises of serum creatinine; eleven of these were on maintenance haemodialysis, and three were successful renal transplant recipients. Clinical findings, including pruritus and xerosis which affected 48% and 60%, respectively, of the patients overall, correlated strongly with severity of renal failure. Histological examination revealed endothelial cell activation and/or necrosis, basement membrane zone thickening, and reduplication of the basal lamina involving both venules and arterioles in all specimens. The microangiopathy was severe in 18 of 24 (75%) of the uraemic specimens, but severity correlated poorly with serum creatinine level, haemodialysis status, or known duration of renal failure, except that it was less severe in the first 2 years (p < 0.02). In contrast, the microangiopathy was very much less severe in the transplant recipients than in haemodialysed patients (p < 0.02) and, in the patient studied both before and after transplantation, changes regressed from severe to moderate within 2 months of transplantation. Other histological findings present in many specimens did not correlate with vessel changes. The findings establish the existence of a potentially reversible microangiopathy in normal-looking skin of patients with chronic renal failure. Further study is needed to determine if it reflects the same pathological process that underlies the development of accelerated atherosclerosis responsible for about half the deaths among patients on maintenance haemodialysis.

Adolescent↗
PubMed1980

Growth of human keratinocytes on fibronectin -coated plates.

Keratinocytes derived from the skin of newborns and of adults aged 19 to 57 years were grown on plates coated with human fibronectin (HFN) in the absence of a 3T3 monolayer. The cells grew well, attained confluence and could be sub-cultivated at densities approximately 10% of those necessary for successful cultivation of human keratinocytes on collagen coated dishes. Growth was excellent at concentrations of fetal bovine serum (FBS) as low as 5%, and appreciable growth occurred over a six day period even in the complete absence of serum. Growth was enhanced by addition of cholera toxin to the medium. Fibroblast overgrowth of the keratinocyte colonies was not observed. The observation that keratinocytes grow well on fibronectin in the absence of a fibroblast feeder-layer should simplify further study of this fastidious cell type and increases our understanding of keratinocyte growth requirements in vitro.

Adult↗