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Biomedical subjects

R M Lavker

Publications and source records attributed to R M Lavker.

At least 19 recordsLinked to original sources
PubMed1992

Effects of topical ammonium lactate on cutaneous atrophy from a potent topical corticosteroid.

BACKGROUND: Topical corticosteroids produce atrophic changes in skin, including thinning of the epidermis and decrease in dermal ground substance. We observed that 12% ammonium lactate produced an increase in the thickness of epidermis and increased amounts of dermal glycosaminoglycans. OBJECTIVE: Our purpose was to determine whether 12% ammonium lactate could minimize cutaneous atrophy produced by a potent topical corticosteroid. METHODS: Clobetasol propionate, 12% ammonium lactate, and both agents were repetitively applied under occlusive patches as well as in open patches on the forearms of human volunteers for 3 to 4 weeks. Biopsy specimens were analyzed for thickness of the epidermis and dermal glycosaminoglycans by image analysis. RESULTS: Twelve percent ammonium lactate produced a significant sparing of atrophy in both the epidermis and dermis without any influence on the bioavailability or antiinflammatory properties of the corticosteroid. CONCLUSION: Twelve percent ammonium lactate may be useful in mitigating the adverse effects of corticosteroid on skin.

Administration, Topical↗
PubMed1991

Ultrastructure of the human vomeronasal organ.

Virtually all vertebrates have a vomeronasal system whose involvement in pheromone detection plays a crucial role in reproduction. In humans, the vomeronasal organ has been assumed to be vestigial or absent and without functional significance. In the present study involving over 400 subjects, vomeronasal pits were observed in all individuals except those with pathological conditions affecting the septum. Electron microscopy of the adult human vomeronasal organ indicates the presence of two potential receptor elements in the pseudostratified epithelial lining: microvillar cells, and unmyelinated, intraepithelial axons. In addition, unmyelinated axons are common in the lamina propria surrounding the organ. They appear to constitute the components essential for a functional chemosensory system, and may thus provide the basis for a pheromone detection system as in other animals.

Adult↗
PubMed1991

The human skin: fragrances and pheromones.

Non-human mammalian pheromones are commonly used as perfumery ingredients. The actual purpose for using these compounds is as a fixative or carrier for the odor effects of the other ingredients as well as a contributor, in part, to the over-all scent of the perfume. Although such materials are used for their fixative and odor qualities rather than their pheromonal effects, perfumes are generally marketed as having the ability to enhance sexual attractiveness. While providing a scent may elicit a positive pleasant response, this should not be confused with a pheromone response. The attractive effect of perfumes is principally related to the effect of the pleasant scent. A more logical approach would be to use human pheromones which, for humans, are both more natural and more effective as true sensual attractants. It seems likely that implementation of this approach will constitute an important paradigm in the perfume industry as perfumery moves from the realm of art to that of science.

Administration, Cutaneous↗
PubMed1991

Extracellular localization of human connective tissue mast cell granule contents.

In early phases of cutaneous inflammation, connective tissue mast cell degranulation is associated with apparent secretion and externalization of immunoreactive chymotryptic serine proteinase. To determine whether this event is associated with structural evidence of granule externalization, we studied the sequential evolution of IgE-mediated hypersensitivity in vivo, as well as mast cell degranulation provoked by a variety of stimuli in cultured explants of human skin. By 1 min after intradermal antigen challenge with ragweed extract, mast cell degranulation was associated with apparent extrusion of intragranule constituents into the pericellular connective tissue. Similar features typified cultured skin explants exposed for 45 min to anti-IgE and other mast cell secretagogues (morphine sulfate, calcium ionophore A23187, compound 48/80, and substance P). Once externalized, granule constituents could be identified within the dermal matrix by their rounded contour and structural similarity to solubilized granule matrices remaining within actively secreting cells. These data indicate that externalization of connective tissue mast cell granule contents occurs early after secretagogue exposure, potentially accounting for infrequent documentation of this event in naturally occurring dermatoses. The ability to recognize externalized granule products at a morphologic level should facilitate the understanding of interactions between mast cell-derived mediators and target structures of the dermal microvasculature.

Adult↗
PubMed1991

Cytotoxic folliculitis in GvHD. Evidence of follicular stem cell injury and recovery.

Recent observations indicate that stem cells of the murine hair follicle exist exclusively as a subpopulation of relatively undifferentiated outer root sheath cells located in the bulge region at the mid-portion of the follicle. Because it has been hypothesized that stem cells of interfollicular epidermis may represent targets of cytotoxic responses in acute graft-versus-host disease (AGVHD), we studied murine AGVHD and observed sequential skin biopsies for the presence and evolutionary pattern of follicular injury. Highly purified subsets of donor T cells were used to produce AGVHD to multiple minor histocompatibility (H) antigens in two strain combinations of mice matched for the major histocompatibility complex (MHC). In the C3H.SW- greater than B6 strain combination, only CD8+ effector cells produced histologic evidence in skin of AGVHD, which peaked three weeks post-transplant. In the B10.D2- greater than DBA/2 strain combination, CD4+ effector cells, and to a lesser extent, CD8+ cells, mediated disease, which peaked during the fourth week post-transplant. Analysis of skin from both strain/effector cell combinations revealed follicular infiltrates preferentially involving follicular stem cell (FSC) regions (bulge) of anagen follicles between the second and third weeks post-transplant. These infiltrates often preceded infiltration of adjacent interfollicular epidermis and were associated with follicular involution to telogen (resting) phase. By the fourth week post-transplant, greater than 50% of follicles were in telogen phase and residual inflammation was minimal. This provided a unique opportunity to observe follicular recovery from telogen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Role of laminin in localization of human dermal mast cells.

Human connective tissue type mast cells (CTMC) are frequently located in close proximity to microvascular and neural basement membranes (BM). We have explored the interaction between human dermal connective tissue-type (chymase positive) mast cells and laminin, a component of BM. In this report, we document that normal CTMC express laminin receptors and are intimately associated with laminin of BM in vivo and pericellular laminin complexes in vitro. Upon degranulation in vitro, CTMC-laminin complexes dissociate and CTMC do not adhere to laminin substrates. In cutaneous mastocytosis/urticaria pigmentosa, CTMC do not express laminin receptors detectable by immunohistochemistry, and are frequently not in close association with laminin of vascular BM. These same features could be induced by degranulation of normal mast cells in organ culture. These findings indicate that CTMC-laminin interactions may be important determinants of mast cell localization in tissue compartments.

Basement Membrane↗
PubMed1991

Hairless micropig skin. A novel model for studies of cutaneous biology.

Reported here is the structural and immunohistochemical similarities between the Yucatan hairless micropig (HMP) skin and that of humans. Hairless micropig skin surface was composed of complex intersecting furrows that created geometric patterns remarkably similar to human skin surface glyphics. The dermal--epidermal interface consisted of undulant downgrowths that interdigitated with dermal papillae. Hairless micropig epidermis contained two morphologically distinct populations of basal keratinocytes (serrated and nonserrated). Similar heterogeneity has been seen only in human epidermis and primate palmar epidermis. Immunohistochemistry revealed that the HMP epidermis is reactive with monoclonal and polyclonal antisera to keratin proteins. Melanocytes reactive with antisera to S-100 protein, as in human skin, also were observed in HMP epidermis. Organization of dermal extracellular matrix, including collagen and elastic fibers, and the organization and reactivity of the microvasculature with antisera to factor VIII, were consistent with human skin. The costicosteroid-induced atrophy and subsequent rebound phenomenon after withdrawal of steroid observed in HMP skin was similar with that observed in humans. It is concluded that HMP skin approximates human skin significantly more precisely than most existing species and is an excellent model for studies of cutaneous physiology and pharmacology.

Animals↗
PubMed1991

Relative proliferative rates of limbal and corneal epithelia. Implications of corneal epithelial migration, circadian rhythm, and suprabasally located DNA-synthesizing keratinocytes.

An important element of the recently proposed limbal stem cell model is that corneal epithelial cells migrate centripetally. The driving force for this migration is unknown, although it has been suggested that limbal epithelium, proliferates at a higher rate than central corneal epithelium, thus creating a population pressure toward the central cornea. This hypothesis was tested by measuring the relative proliferative rates of limbal and central corneal epithelia using 3H-thymidine autoradiographic techniques. The results indicate that, in both the New Zealand white rabbit and SENCAR mouse, the labeling index (LI) of limbal epithelium is actually lower than that of central corneal epithelium. This difference in LI persists throughout the circadian rhythm cycle. These results suggest that population pressure per se cannot be responsible for the centripetal migration of corneal epithelium and raise the possibility that preferential desquamation of central corneal epithelium may "draw" peripheral cells toward the central cornea. In both epithelia, the LI peak precedes the mitotic index (MI) peak during circadian cycle by 4-6 hr. These data therefore are in close agreement with earlier results on several nonocular stratified epithelia but contradict an earlier suggestion that the LI and MI peaks of corneal epithelium coincide. Finally, although most of the 3H-thymidine incorporating cells in central cornea may appear to be suprabasally located, they are only partially displaced into the suprabasal compartment. In most cases, such cells are still connected with the basement membrane through a thin stalk of cytoplasm. Since corneal epithelium rests on an exceptionally flat and rigid substratum, an increase in cellular volume in DNA-synthesizing cells may not be tolerated well in an already crowded basal layer. This may explain why an unusually large proportion of DNA-synthesizing cells are expelled preferentially into either a "second tier basal layer" or into the suprabasal compartment.

Animals↗
PubMed1990

Label-retaining cells reside in the bulge area of pilosebaceous unit: implications for follicular stem cells, hair cycle, and skin carcinogenesis.

Inconsistent with the view that hair follicle stem cells reside in the matrix area of the hair bulb, we found that label-retaining cells exist exclusively in the bulge area of the mouse hair follicle. The bulge consists of a subpopulation of outer root sheath cells located in the midportion of the follicle at the arrector pili muscle attachment site. Keratinocytes in the bulge area are relatively undifferentiated ultrastructurally. They are normally slow cycling, but can be stimulated to proliferate transiently by TPA. Located in a well-protected and nourished environment, these cells mark the lower end of the "permanent" portion of the follicle. Our findings, plus a reevaluation of the literature, suggest that follicular stem cells reside in the bulge region, instead of the lower bulb. This new view provides insights into hair cycle control and the possible involvement of hair follicle stem cells in skin carcinogenesis.

Animals↗
PubMed1990

Release of histamine and tryptase during continuous and interrupted cutaneous challenge with allergen in humans.

To help in understanding the patterns of in vivo mediator release in human allergic skin reactions, we have used a skin chamber model to challenge the denuded bases of skin blisters of 11 sensitive subjects with pollen antigens (Ags) and codeine (C), a mast cell degranulator. Challenges were performed either (1) continuously for 6 hours or (2) in an intermittent fashion that is, Ag or C for the first hour, buffer for the next 4 hours, and then Ag or C during the sixth hour. Fluids in the overlying chamber were assayed for levels of the mast cell components, histamine and tryptase. There was peak release of both histamine and tryptase during the first hour of Ag incubation (89 +/- 11 ng/ml and 1428 +/- 260 ng/ml, respectively). At continuous Ag-challenge sites, there was a plateau of histamine levels (8.0 to 9.5 ng/ml) during the next 4 hours, whereas tryptase levels decreased progressively to baseline levels. Challenge of continuous Ag-incubation sites with C, a mast cell activator, led to another peak release of both histamine and tryptase. At interrupted Ag-challenge sites, histamine levels decreased abruptly, and tryptase levels decreased progressively after the first hour. Rechallenge of such sites with Ag during the sixth hour induced a peak release of histamine but no increase in tryptase levels. Continuous challenge with C for up to 5 hours in other sites induced an initial peak histamine release without a subsequent plateau. However, such a plateau of histamine (but not tryptase) release occurred after an initial C challenge if Ag was subsequently incubated in a continuous fashion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Substance P induces the expression of an endothelial-leukocyte adhesion molecule by microvascular endothelium.

Leukocyte trafficking in normal and diseased skin appears to be initially governed by endothelial surface glycoproteins that promote adhesive interactions with circulating leukocytes. In a separate study, we have demonstrated that one of these glycoproteins, endothelial-leukocyte adhesion molecule-1 (ELAM-1), is rapidly induced on postcapillary dermal venules as a direct consequence of experimentally-elicited degranulation of adjacent mast cells (Proc Natl Acad Sci USA 86:8972-8976, 1989). A principle endogenous mediator of mast cell degranulation is the neuropeptide substance P. In this study, we exposed organ cultures of neonatal human foreskins for 45 min to substance P or to a substance P analogue (D-pro4, D-trp7,9)SP(4-11) that binds to the identical mast cell surface receptor but which does not provoke histamine release. Dermal mast cells were uniformly degranulated only in explants exposed to substance P, as judged by ultrastructural analysis. After subsequent culture in medium alone for 6 h, superficial venules of explants exposed to substance P showed evidence of ELAM-1 induction, as documented histochemically using H4/18 monoclonal antibody. ELAM-1 was not induced by substance P analogue. Furthermore, preincubation of explants with analogue or with the mast cell inhibitor, cromolyn sodium, abrogated the ability of substance P to induce ELAM-1. From these results we suggest that substance P endogenously released by dermal nerve fibers upon physiologic or electrical stimulation may be important in the regulation of endothelial-leukocyte interactions in vivo. This concept provides further evidence for a neurogenic and psychogenic modulation of the immune response, and may be relevant to the course of naturally occurring dermatoses (e.g., psoriasis) that are commonly exacerbated by emotional stress.

Cell Adhesion Molecules↗
PubMed1989

Existence of slow-cycling limbal epithelial basal cells that can be preferentially stimulated to proliferate: implications on epithelial stem cells.

Despite the obvious importance of epithelial stem cells in tissue homeostasis and tumorigenesis, little is known about their specific location or biological characteristics. Using 3H-thymidine labeling, we have identified a subpopulation of corneal epithelial basal cells, located in the peripheral cornea in a region called limbus, that are normally slow cycling, but can be stimulated to proliferate in response to wounding and to a tumor promotor, TPA. No such cells can be detected in the central corneal epithelium, suggesting that corneal epithelial stem cells are located in the limbus. A comparison of various types of epithelial stem cells revealed a common set of features, including their preferred location, pigment protection, and growth properties, which presumably play a crucial role in epithelial stem cell function.

Animals↗
PubMed1989

Degranulation of human mast cells induces an endothelial antigen central to leukocyte adhesion.

To understand better the role of mast cell secretory products in the genesis of inflammation, a system was developed for in vitro degranulation of human mast cells in skin organ cultures. Within 2 hr after morphine sulfate-induced degranulation, endothelial cells lining microvessels adjacent to affected mast cells expressed an activation antigen important for endothelial-leukocyte adhesion. Identical results were obtained when other mast cell secretagogues (anti-IgE, compound 48/80, and calcium ionophore A23187) were used. Induction of this antigen was abrogated by preincubation with cromolyn sodium, an inhibitor of mast cell secretion, and by antiserum to tumor necrosis factor alpha. These findings indicate that degranulation of mast cells activates dermal endothelium through tumor necrosis factor-dependent mechanisms. This event may be critical to the elicitation phase of cutaneous inflammation.

Adult↗
PubMed1989

Morphology of aged skin.

Despite an overall thinning of the epidermis and focal areas of cytologic atypia, there was no morphologic evidence that the protective function of this tissue was compromised by age. The characteristic morphologic markers associated with the keratinization process were not altered either in appearance or in amounts. A well-formed stratum corneum was present, suggestive that barrier ability is not compromised in senile skin. Whereas alterations in the aged epidermis are slight, the dermal-epidermal changes are marked and have greater physiologic consequences. The major change is a relatively flat dermal-epidermal junction because of retraction of the epidermal papillae as well as the microprojections of basal cells into the dermis. This flattening results in a more fragile tissue that is less resistant to shearing forces. Retraction of the epidermal downgrowths may also explain the loss in proliferative capacity associated with the aged epidermis. The major alterations in the aged dermis concern the architecture of the collagen and elastin networks. Both fibrous components appear more compact because of a decrease in the voids or spaces between the fibers; the spaces resulted from a loss of ground substance. Collagen bundles appear to unravel, and the individual elastic fibers show signs of elastolysis. The net effect of these fibrous rearrangements and alterations is a dermis that is less stretchable, less resilient, more lax, and prone to wrinkling.

Aging↗