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Biomedical subjects

A S Zelickson

Publications and source records attributed to A S Zelickson.

At least 19 recordsLinked to original sources

Treatment of photoaged skin with topical tretinoin increases epidermal-dermal anchoring fibrils. A preliminary report.

Topical 0.1% tretinoin or vehicle control was applied daily to the forearm skin of six caucasian adults for 4 months. Two-millimeter punch biopsy specimens were obtained from treatment sites at the beginning and end of the study period for electron microscopy. Anchoring fibrils within the epidermal-dermal junction of skin treatment sites were quantitated by blinded, standardized, computer-assisted morphometry. After 4 months of continual daily treatment, skin sites that received topical tretinoin showed double the anchoring fibril density compared with vehicle control sites (1.34 anchoring fibrils per micron of lamina densa vs 0.65, respectively). The possible mechanisms by which topical tretinoin increases anchoring fibrils in skin include the drug's property of inhibiting collagenase, a dermal enzyme that degrades anchoring fibril collagen. We speculate that increased numbers of collagenous anchoring fibrils within the papillary dermis of human skin is one of the connective-tissue correlates of the clinical improvement observed in photoaged skin after treatment with topical tretinoin.

Administration, Cutaneous

Sustained improvement with prolonged topical tretinoin (retinoic acid) for photoaged skin.

We performed a 22-month trial of topical tretinoin (retinoic acid) in the treatment of photoaging. Thirty patients participated in a 4-month, randomized, blinded, vehicle-controlled study that has been reported previously; 21 patients continued tretinoin therapy on an open-label basis, participating in the study for a total of 10 months, and 16 patients continued for 22 months. During the open-label study, the statistically significant improvement that had occurred in fine and coarse wrinkling and skin texture during our original study was sustained, despite reductions in dose or frequency of application of tretinoin. The number of discrete lentigines decreased by 71% compared with the number before therapy. Histologic findings included a statistically significant thickening of the epidermis. Side effects were limited to a cutaneous retinoid reaction that diminished as therapy proceeded.

Administration, Topical

Linear focal elastosis (elastotic striae).

Three patients are described who had a distinctive clinical and histologic presentation of dermal elastosis. Sunlight apparently played little role in the development of this elastotic change. To the best of our knowledge, this is the first report of this form of elastosis.

Aged

Transdermal delivery of salicylic acid in the treatment of viral papillomas.

Healthy adult (New Zealand, Dutch Belt, and Wild) rabbits were infected with rabbit papilloma virus (Shope variety). The resultant papillomas were treated with salicylic acid in a new transdermal drug delivery system utilizing a karaya gum glycol matrix. Biopsy samples of treated papillomas were taken at 1, 2, and 3 weeks after initiation of treatment and examined by electron microscopy. The observed changes during the course of treatment indicated that the karaya gum glycol matrix effectively released salicylic acid into the stratum corneum. Further, the rate of delivery of salicylic acid was such that the desired keratolytic activity was achieved with minimal inflammatory response.

Administration, Cutaneous

Intracellular elastin in generalized granuloma annulare.

This report reviews thirteen cases of generalized granuloma annulare. The light and electron microscopic appearance of intracellular elastin particles in eleven of these cases is described. These bodies were also noted in deep granuloma annulare, elastosis perforans serpiginosa, and a small percentage of localized granuloma annulare. They were not found in necrobiosis lipoidica.

Adult

Ultrastructural changes in sebaceous glands following treatment of cystic acne with isotretinoin.

Following 20 weeks of treatment with isotretinoin, sebaceous glands in patients with cystic acne shrank in size. The cells remaining in the sebaceous lobules were mainly mature lipid-filled cells, with some undifferentiated cells still present at the periphery. The ultrastructure of the glands 8 weeks after cessation of treatment was directly related to the drug dose given each patient. The larger the dose, the slower the return to pretreatment morphology. In those patients given a lower dose, most of the glands observed 2 months after treatment was stopped were similar in size to those seen prior to treatment.

Acne Vulgaris

Melanocyte changes following PUVA therapy.

The effect of psoralens and long-wave ultraviolet light (PUVA) therapy on human melanocytes was studied at the ultrastructural level. The results demonstrate an increase in the number of melanocytes, a change in their location, and an increase in the size of the melanosomes. Significantly, some of the melanocytes extend in narrow columns deep into the dermis, limited by the basal lamina, while others are found free within the dermis. Other morphologic alterations in the melanocytes consist of abnormal mitochondria, a swollen and distorted endoplasmic reticulum, and large lysosomes. The aforementioned abnormalities were also present in PUVA-treated skin that was examined 15 months after the treatment had been stopped.

Furocoumarins

Giant melanosomes in multiple lentigines syndrome.

Biopsy specimens of normal skin and lentigines from an 82-year-old man with multiple lentigines syndrome were examined with light and electron microscopes. Giant melanosomes were found in dermal melanophages, melanocytes, and keratinocytes in all epidermal layers. Morphologic characteristics of these melanosomes are described, and other conditions in which they have been found are discussed.

Aged

Depressed immune function in epidermodysplasia verruciformis.

Epidermodysplasia verruciformis (EV) is a rare disease characterized by the early onset and unremitting progression of wart-like lesions and frequent association of cutaneous carcinomas. We report two siblings with EV. Immunologic study of both patients demonstrated normal immunoglobulin levels, normal numbers of T-lymphocytes and B-lymphocytes, but markedly depressed in vitro blastogenic reactivity to mitogens and antigens. Cutaneous anergy to a variety of common skin test antigens was noted. These observations may reflect an inherited abnormality in immune function, or the depressed immune function may result from the viral infection of EV.

Adult

Netherton's syndrome: an electronmicroscopic study.

An ultrastructural study of 2 patients with Netherton's syndrome (bamboo hair, scaling dermatosis, and an atopic diathesis) showed features of psoriasis and a dermatitis. Although the biopsies from the patients showed histological and ultrastructural similarities, the clinical presentations were different. One patient had ichthyosis linearis circumflexa, while the other had a generalized ichthyosiform eruption. The ultrastructural findings in the 2 patients, while not specific, may help distinguish the eruption of Netherton's syndrome from other scaling dermatoses.

Adult

Effects of topical fluorouracil on normal skin.

Daily application of 1% fluorouracil cream to normal white skin results in definite morphologic alterations of the epidermis. Although clinical changes were not present, electron microscopic examination of the tissue demonstrates changes especially pronounced in the epidermal keratinocytes. These changes consist of cytoplasmic vacuoles, alterations in the mitochondria, Golgi complex, and endoplasmic reticulum, as well as widened extracellular spaces.

Administration, Topical

Keratinosomes in psoriatic skin.

Keratinosomes in psoriatic skin can be slightly larger than those in normal skin. Some seem to develop an unusual internal morphology, and some reach their full development while they are still within the immediate Golgi area. Observational evidence indicates that there may be more kerantinosomes in psoriatic skin than are generally found in normal skin. Keratinosomes appear extracellularly from the spinous layer through the horny layer. Some keratinosomes do not move to the outside of the cell and can be seen within cells of the horny layer. There appears to be an increased number of keratinosomes in and between the outer cells of sweat ducts. Keratinosomes are also present within the dark cells of the duct and the extracellular space between the dark cells contains material from keratinosomes.

Cytoplasmic Granules

Embryology of the epidermis: ultrastructural aspects. 1. Formation and early development in the mouse with mammalian comparisons.

A detailed light and electron microscopic study of the cellular morphology of developing epidermis in the 7 to 12 day mouse embryo reveals that a single layer of ectoderm is not present until day 8. The 8-day embryonic epithelium is characterized by the presence of microvilli, apical attachment specializations, developing desmosomes and a thin, immature basal lamina. The 9-day embryonic epithelium is flatter and has both an increased number of microvilli on the surface and an increased number of microtubules in association with developing desmosomes. On day 10, numerous developing desmosomes are associated with fine filaments in the regions of the attachment plaques. Occasional peridermal cells are present on day 11. Numerous granules are associated with the inferior cell membranes of the superficial or uppermost cell processes. In the 12-day embryo, the periderm forms a complete layer. A skein of fine filaments is present just inside the basal cell membrane of the germinative cells and microtubules are more abundant in the basal cell cytoplasm.

Animals

Embryology of the epidermis: ultrastructural aspects. II. Period of differentiation in the mouse with mammalian comparisons.

A detailed light and electron microscopic study of the cellular morphology of the epidermis in the 13 through 16 day mouse fetus reveals that an occasional intermediate cell is interposed between the basal and peridermal layers on day 13. All layers are mitotically active. Tonofilaments, unassociated with desmosomes, are present within the basal cell cytoplasm and the mitotic axis of the basal cells has changed from a parallel to a perpendicular plane with respect to the epidermal surface. At 14 days, a complete stratum intermedium, composed of one or two cell layers, is present. Rarely, developing hemidesmosomes are observed. Pools of glycogen are present in all cells below the periderm. The periderm is dense and no longer mitotically active. The skein of filaments, present in the inferior cytoplasmic region of the basal cells on days 12 and 13, is now absent. In the 15 day fetus, numerous developing hemidesmosomes are present. The stratum intermedium contains three to four layers of cells, and filaments are located deep within the cytoplasm of these intermediate cells. Rarely, a few developing keratohyalin granules and keratinosomes are present. A stratum intermedium is no longer present in the 16 day fetus. This region is now composed of a stratum spinosum and a stratum granulosum. Numerous keratinosomes are located in the upper stratum spinosum and lower stratum granulosum. The cells in the stratum granulosum are nucleated and the uppermost cells contain large keratohyalin granules. Three heterogeneous and one homogeneous type of keratohyalin granule is described. Dense bodies are present within mitochondria, nuclei, glycogen pools and the peridermal cytoplasm. The periderm is no longer dense and glycogen and keratohyalin granules are not observed in this layer.

Animals

Embryology of the epidermis: ultrastructural aspects. III. Maturation and primary appearance of dendritic cells in the mouse with mammalian comparisons.

The epidermis of mice ranging in age from prenatal day 17 through postnatal day 4 and, in addition, postnatal day 18, was studied with the electron microscope. In the 17 day fetus, the periderm may or may not be present and a stratum corneum is developing in the latter case. The cells of the strata spinosum and granulosum contain much glycogen and many keratinosomes and homogeneous keratohyalin granules which appear to line up in a row near the distal cell membranes, fuse and form keratinized cells which contain material similar in density to that of the individual keratohyalin granules. In the 18 to 20 day fetuses, no periderm is present. The stratum corneum becomes well-developed. The quantity of glycogen decreases but the number of keratinosomes and keratohyalin granules increases. Some cells in the basal region contain necrotic phagocytosed cells. Few changes occur in the epidermis of the neonate, although the stratum corneum increases in thickness. In the early postnatal period, the mouse epidermis is mature in appearance and resembles that of man. By postnatal day 18, the whole epidermis is much thinner, although all classical strata can usually be identified. The primary appearance and subsequent maturation of epidermal dendritic cells was also studied in the mouse during the embryonic, fetal, early postnatal and 18 day postnatal periods. Melanocytes which lacked cell processes were first identified in the 15 day fetus. Melanocyte cell processes and an increasing number of melanosomes, as well as melanocytes, are present between prenatal day 18 and postnatal day 3. On postnatal day 4, fewer melanocytes are present and they contain vacuoles. Phagocytosed melanocytes are also present within basal keratinocytes. Undifferentiated dendritic cells or indeterminate cells are observed beginning on prenatal day 16. These cells do not appear to increase significantly in number subsequently. On postnatal day 18, Langerhans cells and indeterminate cells are present but no melanocytes can be identified. No Merkel cells were observed. Mitotic dendritic cells or dendritic cells traversing the basal lamina were not observed.

Age Factors