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Biomedical subjects

R M Lavker

Publications and source records attributed to R M Lavker.

At least 91 records · Page 5Linked to original sources
PubMed1985

Anatomy of striae.

The histopathology of striae distensae is disputed; different authorities give contradictory accounts of the microscopic changes, especially in elastic fibres. We re-evaluated the problem by taking eight elliptical biopsies across striae. Six were examined by light microscopy with appropriate stains for elastin and collagen. Two were prepared for scanning electronmicroscopy (s.e.m.), using a procedure which removes collagen, enabling the elastic network to be seen in its native form. By light microscopy, striae were sharply demarcated from normal skin, consisting mainly of fine, straight bundles of collagen arranged parallel to the surface. Fine elastic fibres were disposed similarly without fragmentation, fraying or curling. By s.e.m., the elastic network was found to be extraordinarily dense and well developed with many fine, curled fibres in random array. It was evident that the routine stains for elastin greatly underestimated the abundance of elastic fibres, probably because immature fibres contain insufficient protein matrix. The horizontal packing of collagen bundles was confirmed by s.e.m. These findings support the view that striae distensae are scars. There is no evidence that they form by stress-induced rupture of the connective tissue.

Adult↗
PubMed1985

The anatomy and pathogenesis of wrinkles.

The anatomy of linear wrinkles ("crow's feet' and temporal frown lines), fine criss-cross wrinkles of the face and wrinkling of the general body surface of elderly persons, was studied by light and scanning electron microscopy. No histological features distinguished the various wrinkles from surrounding skin. It was concluded that the wrinkle is a configuration change, like the grooves worn into an old glove, without specific structural alterations at the histological level. As regards pathogenesis, the common setting was found to be deterioration of the elastic tissue network. The skin becomes looser, excessive, and loses the ability to snap back to its original state after being deformed.

Aged↗
PubMed1985

Cutaneous mast cell depletion results from topical corticosteroid usage.

The effect of long-term topical application of corticosteroids on human cutaneous mast cells was examined. Two potent corticosteroids, clobetasol-17-propionate and fluocinonide, produced a greater than 85% decrease in histamine content over a 6-wk treatment period, whereas betamethasone valerate, a less potent corticosteroid, produced a 66% decrease. Electron microscopic examination of the biopsies taken from sites after 6 wk of treatment indicate that the reduced levels of histamine were caused by the depletion of mast cells, as evidenced by: the inability to identify any cells representative of mast cells by detailed electron microscopy of the biopsies; and the marked acellularity around the vasculature where mast cells are certain to be detected. Histamine levels did not begin to decline until after 3 wk of corticosteroid treatment, indicating that corticosteroids are not immediately harmful to mast cells. Electron microscopic examination of biopsies taken at the beginning of treatment and 1 wk later showed normal-appearing mast cells, whereas at 3 wk, a small population of mast cells was detected with features usually associated with degenerating or dying cells. These observations suggest that protracted application of corticosteroids to skin is toxic to mast cells. After discontinuation of treatment, the drug-related atrophy associated with chronic application of potent corticosteroids to skin is rapidly reversed, and skin structure returns to near normal by 14 days. Over this time period, however, histamine levels did not increase and mature mast cells could not be observed by electron microscopy. At 14 days post-steroid treatment, the first signs of cells containing sparse amounts of granules having the characteristics of mast cell granules were seen. We interpret this to represent new mast cells beginning to mature in the skin. By 3 mo, histamine levels returned to normal, demonstrating the reversibility of the steroid-induced mast cell depletion. The studies presented here establish the deleterious effects of long-term topical corticosteroid treatment on cutaneous mast cells, and begin to establish a system in which the development of mast cells in tissue can be investigated.

Administration, Topical↗
PubMed1985

Treatment of urticaria pigmentosa with corticosteroids.

Based on a previous observation that the long-term application of potent topical corticosteroids under occlusion to normal skin resulted in the loss of mast cells, we investigated the effects of intralesional and topical steroids in urticaria pigmentosa (UP). Three patients with UP had lesions that were injected with triamcinolone acetonide. Four weeks after injection, all patients showed a loss of Darier's sign, and, by eight weeks after injection, there was a dramatic clearing of the plaques and a decrease in brown hyperpigmentation. By 12 weeks, mast cells were undetectable by light microscopy and transmission electron microscopy (TEM). The injection sites remained dramatically improved for as long as one year after treatment, and histamine content was reduced 95% in one patient 48 weeks after injection. In six patients, the topical application of 0.05% betamethasone dipropionate under occlusion to limited areas induced almost complete clearing of UP lesions. Lesions treated with an emollient under occlusion, as a control, demonstrated no change. After treatment, no mast cells were seen by light microscopy or TEM, and this persisted for at least 24 weeks. There was also a significant decrease in tissue histamine levels in the treated areas. The treated areas remained clinically improved for at least nine to 12 months. These data indicate that steroid therapy dramatically decreases the excess number of normal-appearing mast cells in UP as well as induces a prolonged resolution of UP lesions. Local corticosteroids thus are a useful therapeutic modality for UP.

Administration, Topical↗
PubMed1984

Morphologic investigations on the rebound phenomenon after corticosteroid-induced atrophy in human skin.

Cutaneous atrophy was induced on the forearms of 4 volunteers by continuous occlusive application of clobetasol-17-propionate for 6 weeks, after which time the steroid was discontinued. Epidermal and dermal changes during the subsequent rebound "flare" were monitored for 2 weeks by light and transmission electron microscopy. An exuberant hyperplasia characterized the epidermal response. Within 2 days poststeroid, most basal cells displayed fine structural features typical of highly proliferating cells. "Dark"-staining keratinocytes appeared in large numbers 4 days poststeroid, preceding a 4-fold maximal increase of viable epidermal thickness which occurred at 7 days. The stratum corneum, initially very thin, increased markedly in thickness and displayed the typical basket-weave appearance. By 14 days, Langerhans cells, which were absent immediately poststeroid, were again present. At this time, the epidermis returned to a nearly normal state. Dermal restitution was similarly rapid. Initially, fibroblasts appeared very active as evidenced by widely dilated endoplasmic reticulum filled with flocculent material. Ground substance increased continuously, reaching normal levels by 14 days. An increase in postcapillary venules was noted during the rebound flare. Swift epidermal and dermal changes are evidence that topical corticosteroids are rapidly cleared from the skin. The vigorous epidermal hyperplasia reflects repair of the atrophic, suppressed epidermis as well as a response to desiccation consequent to the loss of the stratum corneum.

Adrenal Cortex Hormones↗
PubMed1984

Studies on the mechanism of clinical tolerance in solar urticaria.

Tolerance to artificial ultraviolet radiation (UVR) was induced in three patients with solar urticaria by administering graded whole body exposures to long-wave ultraviolet radiation (UV-A, 320-400 nm) in a phototherapy cabinet. Plasma histamine levels, mast cell ultrastructure and cutaneous responses to intradermally injected codeine and histamine were examined before and after the induction of tolerance. No evidence of serum complement activation could be demonstrated following exposure of serum samples to UVR in vitro. These studies suggest that the state of tolerance is due neither to mediator (histamine) depletion nor to a systemic effect induced by UV-A but may be due to an increase in the mast cell degranulation threshold.

Adult↗
PubMed1984

Ultrastructural study of iron deposition in the eccrine sweat glands of patients with iron overload.

An ultrastructural study of eccrine sweat glands was carried out on three patients with iron overload (two with idiopathic haemochromatosis and one with transfusional haemosiderosis). In all three patients small electron-dense particles were seen in both eccrine sweat glands and macrophages. They appeared primarily in the clear cells of the eccrine sweat glands as membrane-bound irregularly shaped bodies, and were shown to contain iron by energy dispersive X-ray microanalysis. Iron aggregates in and around sweat glands were also seen on light microscopy.

Adult↗
PubMed1983

Cromolyn does not modulate human allergic skin reactions in vivo.

Cromolyn pretreatment frequently reduces antigen inhalation-induced bronchospasm possibly by inhibiting mast cell degranulation and mediator release. However, the local effects of cromolyn on type I hypersensitivity skin reactions are not well understood. We studied the effect of local cromolyn on antigen-induced skin reaction, histamine release, cellular inflammatory response, and ultramicroscopic changes of mast cells in 10 ragweed-sensitized subjects. Results showed that cromolyn 2% (nonirritant dose) does not modulate ragweed-induced skin whealing response, histamine release, and ultramicroscopic changes of mast cells. Thus, unlike the situation in the tracheobronchial tree, allergic skin reactions and associated events are not inhibited by local cromolyn application.

Adult↗
PubMed1983

Rapid modulation of keratinocyte differentiation by the external environment.

The ultrastructural differentiation of epidermal keratinocytes cultured in the presence of 3T3 feeder cells is significantly different from that of the epidermis in vivo. Several markers of keratinization, including keratohyaline granules (KGs), membrane-coating granules (MCGs), and an enucleated stratum corneum are essentially absent from cultured cells. When cultured rabbit epidermal cells were trypsinized and injected subcutaneously into athymic mice, the cells reaggregated and formed cysts lined with a stratified squamous epithelium morphologically resembling the in vivo epidermis. In this paper, we examined the differentiation of the injected cells by electron microscopy. Within 24 h after injection, MCGs and KGs appeared in the reaggregated epidermal cells. Horny cells were noted within 48 h. Since basement membrane formation was not completed until much later (between 4-9 days), a direct contact between epidermal cells and a continuous basal lamina structure was not required for the formation of various keratinization markers. Glycogen and lipid droplets, which were abundant in the early (10-48 h) cystic epithelia, gradually disappeared from the basal through the granular layers during days 2-9. By 16 days, the ultrastructure of the cystic epithelium appeared similar to the in vivo rabbit epidermis including the formation of "rabbit-type" KGs, MCGs, and normal enucleated horny cells. These results provided further evidence that the differentiation of epidermal cells can be modulated significantly and reversibly by the external environment. Moreover, the expression of certain morphologic markers of keratinization (KGs and MCGs) can be modulated rapidly by the growth environment.

Animals↗
PubMed1983

Epidermal stem cells.

Stem cells are by definition present in all self-renewing tissues and are believed to play a central role in cell growth and differentiation. Existing evidence suggests that a subpopulation of epidermal basal keratinocytes represents stem cells; however, these cells have never been positively identified. In this paper we review evidence that in monkey palm epidermis there exist two morphologically distinct subpopulations of basal keratinocytes that are spatially segregated. One population, located in the shallow rete ridges, is characterized by a cytoplasm filled with tonofilaments and a highly convoluted ("serrated") dermal-epidermal junction; these cells may play a role in anchoring the epidermis to the dermis. In contrast, the other population, located at the tips of deep rete ridges, is characterized by a "primitive" cytoplasm containing abundant melanosomes and a relatively flattened ("nonserrated") dermal-epidermal junction. Tritiated thymidine labeling experiments suggest that the nonserrated basal keratinocytes are slow-cycling; however, a highly proliferative population of keratinocytes can be identified immediately above these basal cells. These findings are consistent with the concept that the nonserrated basal keratinocytes may represent stem cells that give rise to suprabasally located, transient amplifying cells before undergoing terminal differentiation. Monkey palm epidermis provides a model system for further studies of primate epidermal stem cells.

Animals↗
PubMed1983

Corticosteroid atrophy in human skin. A study by light, scanning, and transmission electron microscopy.

Steroid atrophy was induced in 3 volunteers by the continuous, occlusive application of clobetasol propionate to the forearms for 6 weeks. The changes were followed sequentially by light, scanning, and transmission electron microscopy. a 59% decrease in viable epidermal thickness was noted after the sixth week of treatment, as well as a flattening of the dermal-epidermal junction. The 3-dimensional architecture of the dermis was strikingly reorganized. This was largely brought about by resorption of the ground substance as revealed by a progressive diminution of Hale's stain for acid mucopolysaccharides. Loss of ground substance resulted in decreased spaces between collagen and elastic fibers as shown by scanning and transmission electron microscopy. The fibrous network consequently collapsed, yielding a more compact papillary and reticular dermis. This compression caused the reorientation of both collagen and elastic fibers. However, no differences in collagen and elastin fine structure were noted. Fibroblasts were shrunken but not reduced in density. A marked decrease in number of mast cells was noted in 3-week specimens and virtually no mast cells were observed after 6 weeks. We found that the primary effect of short-term steroid use was a rearrangement of the geometry of the dermal fibrous network. This was not due to alterations in the fibers themselves but a secondary consequence of the loss of ground substance.

Adrenal Cortex Hormones↗
PubMed1983

Effect of cimetidine on exogenous histamine inhibition of histamine release in vivo.

We previously reported that exogenous histamine inhibits in vivo histamine release and eosinophil accumulation in ragweed-challenged skin sites of sensitive human subjects. The mechanism(s) involved were unclear. In this study, we repeated similar approaches in four of the same subjects pretreated for 3 days with cimetidine, an H2 receptor antagonist. The pattern of exogenous histamine effects was now different in that local exogenous histamine (50 ng/ml) did not significantly alter ragweed-induced mast cell alteration, histamine release, or the degree of eosinophil accumulation in skin challenge sites. These findings suggest that the observed exogenous histamine inhibitory effects may be mediated through the H2 receptor.

Biopsy↗
PubMed1982

Redistribution of melanosomal complexes within keratinocytes following UV-A irradiation: a possible mechanism for cutaneous darkening in man.

In contrast to other ultraviolet (UV) wavelengths, UV-A can induce long-term or "true" pigmentation rapidly with little or no latency. The response cannot be clearly separated from immediate pigment darkening and is too rapid in onset to be explained by neomelanogenesis. In order to investigate possible mechanisms for this phenomenon, UV-irradiated skin was examined microscopically and ultrastructurally 18 h postirradiation. Specimens from skin sites tanned by exposure to melanogenic doses of UV-A showed a paradoxical reduction in the degree of basal melanization by light microscopy compared to unirradiated skin. Ultrastructurally, there was migration and dispersion of packaged melanosomes within keratinocytes from their normal, aggregated location around the nucleus towards the periphery of the cell. These changes were not observed in specimens exposed to melanogenic doses of UV-B. We propose that UV-A wavelengths can selectively cause redistribution of melanin-laden organelles within human keratinocytes in vivo and that this phenomenon accounts for the visually observed hyperpigmentation that develops soon after single exposures to these wavelengths. Dispersion of melanosomal complexes may be another mechanism by which UV-radiation (UVR) can induce tanning in human skin.

Adult↗
PubMed1982

On the nature of idiopathic guttate hypomelanosis.

Clinical and morphologic studies were made of 20 cases of guttate hypomelanosis. The sharply demarcated hypopigmented macules were present on both covered and exposed sites, excluding sunlight exposure as a cause. Skin surface replicas and biopsies showed no evidence of post-traumatic or post-inflammatory scarring. The stratum corneum had fewer cell layers, but no abnormalities of keratinization were observed. Light and electron-microscopic and histochemical studies showed only reduced numbers of hypoactive melanocytes. In no case were melanocytes completely absent, excluding vitiligo. Guttate hypomelanosis is a common disorder of unknown origin. The evidence indicates an age-related somatic mutation of melanocytes.

Age Factors↗
PubMed1981

The relationship between bacteria and the abnormal follicular keratinization in acne vulgaris.

The structural organization and bacteriological profile of follicular casts and early comedones in prepuberal children were investigated. Follicular casts were present in all samples but were not as abundant as usually seen in older individuals with acne. When examined with the light microscope, all casts and comedones were composed of numerous layers of horny cells and sebum, but were devoid of bacteria. Neither follicular casts nor comedones yielded bacteria when cultured. Electron microscopy of the follicular casts revealed the presence of small round, discrete lipid droplets, and alternating dense and less dense lamellar configurations within the horny cells. Some horny cells closest to the sebum-filled lumen contained large lipid masses, resulting in "balloon-shaped" regions. Prepuberal follicular horny cells contained all of the abnormalities usually seen in follicular casts and biopsy material from acne patients, which suggests that these casts are potential comedones. These aberrations occurred in the complete absence of bacteria indicating that bacteria are not essential to the formation of casts or comedones. Furthermore, our findings indicate that bacteria play little if any role in the initial events of pathological keratinization.

Acne Vulgaris↗
PubMed1981

The atrophogenic effect of crude coal tar on human epidermis.

The effects of crude coal tar on human epidermis were studied in fourteen healthy young adult males. A 20% reduction in viable epidermal thickness, as determined by computer assisted analytical microscopy, was observed after 40 days of topical treatment. Prior to this long term effect of crude coal tar, an initial transient hyperplasia was observed during the first 2 weeks of treatment. These findings indicate that crude coal tar by itself can act as a cytostatic agent on normal human skin, when applied intensively.

Adult↗
PubMed1981

In vivo release of eosinophil chemoattractant activity in human allergic skin reactions.

A search was made for in vivo release of factor(s) that may be responsible for prominent eosinophil accumulations in human allergic skin reactions. Using a specially designed skin chamber appended to the base of unroofed skin blisters, we have found at ragweed-challenged sites in sensitive subjects the release of significantly greater histamine (15 +/- 3 ng/ml) than at control sites (3 +/- 0.5 ng/ml). Eosinophil accumulation after 2 hr was also significantly greater on membrane filters appended to ragweed-challenged sites than control sites (55 +/- 15 vs 4 +/- 0.5). Intradermal injection of ultrafiltrates of the chamber fluids from antigen-challenged sites, but not of fluids from control sites, induced prominent eosinophil accumulation (mean = 25/mm2) when injected intradermally in autologous uninvolved skin. Neither ultrafiltered antigen solution nor histamine (employed in concentrations similar to those released in the chambers) evoked such in vivo responses when injected intradermally in the same subjects (mean = less than 1/mm2). The eosinophil responses to injected ultrafiltered chamber fluid from antigen-challenged sites peaked at 30 min, whereas even greater eosinophil responses to unaltered antigen started after 60 min. These findings suggest that in vivo release of a low m.w. factor or factors other than histamine is very likely responsible for at least part of the in vivo eosinophil accumulation in human allergic reaction sites. Additional findings suggest that a significant portion of the time lag between intradermal antigen and dermal eosinophil accumulation is encompassed by local mediator release.

Asthma↗