Alvin S. Zelickson

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.

Chediak-Higashi Syndrome: Hereditary Gigantism of Cytoplasmic Organelles

In the Chediak-Higashi syndrome, an anomalous hypopigmentation is associated with large lysosomal granules in the blood leukocytes. Since the inheritance pattern is that of an autosomal recessive trait, we postulated a common mechanism for these two primary features of the disease. Electron microscopy of melanocytes revealed that the pigmentary anomaly is indeed based on giant melanosomes. Since both types of granules, leukocytic and melanosomal, are characterized by limiting membranes, Chediak-Higashi disease may be a genetic disease of membranes.

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.

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.

THE CHEDIAK-HIGASHI ANOMALY AND THE ALEUTIAN TRAIT IN MINK: HOMOLOGOUS DEFECTS OF LYSOSOMAL STRUCTURE*

The Chediak-Higashi syndrome was first described less than 30 years ago and is perhaps one of the most important of genetic diseases for modern cell biology. Beguez-Cesar (1943) and Steinbrinck (1948) published the first case reports, in the Cuban and German literature, respectively, and in 1952 Chediak described the Cuban patients further. Higashi (1954) reported the disease in a Japanese family as well as the results of the first histochemical studies. He appears to have had some inkling of the broad significance of the trait as revealed in his title, “Congenital Gigantism of Peroxidase Granules.” Sato (1955), Higashi’s mentor, first applied the double eponym by which the trait is most commonly known today. A mutation producing an unusual blue-gray cast to the coat color of ranch mink was first observed in 1941. Animals manifesting this recessive trait were soon recognized to be highly susceptible to disease and poor breeders, but fortunately, their color rapidly became highly prized enough to justify the increased economic risk to the mink rancher maintaining these animals. It is to this circumstance that we owe the knowledge that the gene acts to dilute all other colors, and that it is probably not an allele at the albino locus (Shackleford, 1950). Alert veterinary scientists related the Aleutian trait to the ChediakHigashi (CH) trait in 1963 (Leader et al.) , and this same group has reported detecting the trait in a rare strain of purebred cattle (Padgett et al., 1964). It has become increasingly certain that the mink trait is homologous to the human anomaly. Both conditions are based on a single autosomal recessive gene. This is clearly demonstrable in the mink, and is a highly reasonable assumption in the human condition. For example, Kritzler et al. (1964) found that eight out of 16 sets of phenotypically normal parents were consanguinous, ten out of 19 cases reported were male and 29 out of a total of 69 siblings were affected, including the propositi. Sadan et al. (1965) have reported two sibships from consanguinous marriages in a complexly interrelated kinship. They found that assuming the trait to be an autosomal recessive character provided an entirely acceptable pattern of inheritance through six generations involving some 73 persons. Both the mink and the affected children have similar primary phenotypic manifestations and secondary diseases. Primary manifestations easily determinable in very young Aleutian mink as well as in infants with the CH trait are the pigmentary dilution and the anomalous “inclusions” in the leukocytes. As seen in peripheral blood smears, the leukocyte cytoplasmic bodies are usually more or less neutrophilic in neutrophils, basophilic in basophils, and eosinophilic in eosinophils. In addition, lymphocytes and monocytes often have one or several large azurophilic

Brown Ocuuiocutaneous Albinism: Clinical, Ophthalmological, and Biochemical Characterization

The clinical, ophthalmological, and biochemical characteristics of a 28-year-old black woman with brown oculocutaneous albinism were determined. Hair color was medium brown and skin color was light brown, and a faint tan developed with sun exposure. The irides were light brown in the central one-third, blue-gray in the peripheral two-thirds, and showed punctate and radial translucency. Visual acuity was 20/60 in the right eye and 20/100 in the left eye. There was a moderate pendular nystagmus, and previous surgeries had corrected an exotropia. The foveal reflex was muted, and the retinal pigment was reduced. Hairbulb tyrosinase activity was 1.75 pmoles/120 min/hairbulb, hairbulb glutathione content 0.83 nmoles/hairbulb, and urine excretion of 5-S-cysteinyldopa 174.9 ng/mg creatinine. Electron microscopy of hairbulb and skin melanocytes showed arrested melanosomal development. These findings suggest that there is a partial block in the distal eumelanin pathway in this form of albinism. The ophthalmological characteristics of six additional cases of this form of albinism are also presented.

Elastic tissue changes in skin following PUVA therapy.

Treatment of psoriasis with psoralens and high-intensity long-wave ultraviolet light (PUVA) produces changes in the ultrastructure of elastic tissue in skin. Early alterations consist of a loss of elastin followed by a breakdown of the microfibrils and subsequent fragmentation of the elastic fiber. Tissue examined 15 months after treatment was stopped still showed marked ultrastructural changes in the elastic fibers.

Bowenoid papulosis of the penis. Demonstration of intranuclear viral-like particles.

Intranuclear viral-like particles are reported in a case of Bowenoid papules of the penis.

LOCALIZATION OF MELANIN SYNTHESIS WITHIN THE PIGMENT CELL: DETERMINATION BY A COMBINATION OF ELECTRON MICROSCOPIC AUTORADIOGRAPHY AND TOPOGRAPHIC PLANIMETRY.

SummaryLocalization of melanin synthesis within the pigment cells of the Cloudman S-91 mouse melanoma was determined by means of a combination of high resolution autoradiography and topographic planimetry. Initial melanin biosynthesis occurred predominantly in the endoplasmic reticulum and associated ribonucleoprotein particles of the melanocytes. By measuring a number of cell organelles and employing the index of “relative specific localization” it could be shown that the nucleus and mitochondria are of little or no importance in the process of melanogenesis.

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.