Lois Y. Matsuoka

Human plasma transport of vitamin D after its endogenous synthesis.

Transport of vitamin D3 from its sites of cutaneous synthesis into the circulation has been assumed to be via the plasma vitamin D binding protein (DBP). We studied vitamin D transport from the skin in seven healthy volunteers who received whole body irradiation with 27 mJ/cm2 dosage of ultraviolet B light (290-320 nm). Samples of venous blood were collected serially in EDTA and immediately chilled. In KBr, plasma samples were ultracentrifuged to provide a rapid separation of proteins of density < and > 1.3 g/ml. Upper and lower phases and serial fractions were analyzed for vitamin D3 (extraction, HPLC), cholesterol (enzyme assay), and human DBP (hDBP) (radial immunodiffusion). Total plasma vitamin D (basal level < 1 ng/ml) increased by 10 h and peaked at 24 h (9 +/- 1 ng/ml). 98% of the D3 remained at the density > 1.3 layers for up to 7 d, whereas cholesterol (> 85%) was detected at density < 1.3 and all of the hDBP was at density > 1.3. In three volunteers who each ingested 1.25 mg of vitamin D2, the total plasma D2 increased to 90 +/- 32 ng/ml by 4 h, and the D2 was evenly distributed between the upper and lower layers at 4, 8, and 24 h after the dose, indicating a continuing association of the vitamin with chylomicrons and lipoproteins, as well as with hDBP. Actin affinity chromatography removed D3 from plasma of irradiated subjects, indicating the association of the D3 with DBP. These findings indicate that endogenously synthesized vitamin D3 travels in plasma almost exclusively on DBP, providing for a slower hepatic delivery of the vitamin D and the more sustained increase in plasma 25-hydroxycholecalciferol observed after depot, parenteral administration of vitamin D. In contrast, the association of orally administered vitamin D with chylomicrons and lipoproteins allows for receptor-mediated, rapid hepatic delivery of vitamin D, and the reported rapid but less-sustained increases in plasma 25-hydroxycholecalciferol.

Use of topical sunscreen for the evaluation of regional synthesis of vitamin D3

Sunscreens absorb solar radiation and block the cutaneous synthesis of vitamin D3. Because of this property, we tested sunscreens as a research tool for photodependent reactions. The concept was evaluated by determining the segmental body contributions to vitamin D3 production. Twenty-seven healthy, untanned white persons with skin type III applied a sunscreening agent to selected body areas (head and neck, arms, trunk, or legs) to block UVB absorption. Control groups comprised subjects who either covered the whole body with, or did not apply, sunscreen. Serum vitamin D3 was determined 1 hour before and 24 hours after exposure to a suberythemic dose of UVB light (27 millijoule/cm2). Basal vitamin D3 levels were similar among the different groups (mean +/- standard error for the entire population: 2.8 +/- 0.7 ng/ml). Segmental contribution to the UVB-stimulated cutaneous synthesis of vitamin D3 appeared to be largely a function of surface area. Serum vitamin D3 increased significantly (p less than 0.05) in subjects exposing the trunk (13.7 +/- 3.2 ng/ml), legs (11.2 +/- 3.2 ng/ml), and entire body (12.6 +/- 2.8 ng/ml). In subjects exposing the head and neck or arms, the post-UVB vitamin D3 level was higher than the basal level (5.8 +/- 4.0 and 4.5 +/- 2.2 ng/ml), but the difference was not significant (p greater than 0.5). Whole body application of sunscreen completely blocks the vitamin D3 response to UVB. We conclude that short-term (single) application of sunscreens may be used as a simple complementary technique for the evaluation of photodependent reactions in physiologic and pathologic conditions.

The association of potentially lethal neurologic syndromes with scleromyxedema (papular mucinosis)

Two patients with scleromyxedema who had progressive neurologic impairment are described. One patient died, and one required prolonged mechanical ventilation. A review of the literature has produced 24 other cases of scleromyxedema in which neurologic changes were prominent.

Elastoderma — Disease of Elastin Accumulation within the Skin

ELASTIC fibers, which consist of two distinct structures — elastin and the microfibrillar component — are responsible for the elasticity of tissues, such as the skin.1 2 3 4 The understanding of th...

Basal cell carcinoma in black patients.

Fourteen cases of basal cell carcinoma occurring in North American black patients were reviewed. The majority of the lesions were asymptomatic, hyperpigmented, translucent nodules and were correctly diagnosed as being basal cell carcinomas prior to biopsy. All of the lesions except one arose in the sun-exposed areas of the head and neck, indicating that basal cell carcinoma in blacks, as in whites, is related to exposure to ultraviolet light. Microscopic examination revealed changes characteristic of basal cell carcinoma. The response to therapy in our patients was good. There appear to be no histologic or clinical differences in the basal cell carcinomas that arise in black and white patients.

Epidermal autoantibodies in erythema multiforme

We report a case of refractory erythema multiforme associated with atypical epidermal autoantibodies. The patient was a 63-year-old woman with clinical and histologic features of erythema multiforme and a large mediastinal T cell lymphoma. Immunofluorescence studies disclosed high serum titers of cell surface antibodies against epidermal keratinocytes in a pattern typical of pemphigus vulgaris. The epidermal antigen reacting with these circulating antibodies was characterized by incubating 14C-labeled keratinocytes with serum. The patients serum pattern precipitated multiple proteins keratinocytes antigens), but not the 130,000- and 85,000-dalton polypeptides characteristic of pemphigus vulgaris. Thus autoantibodies reacting selectively with non-pemphigus vulgaris epidermal keratinocyte antigens may be the cause of a false-positive immunofluorescence test for pemphigus vulgaris.

Neoplastic erythema nodosum.

We performed immunohistologic studies on a 75-year-old white woman with erythema nodosum (EN) and a systemic lymphoma. A skin biopsy specimen from an EN lesion showed lobular and septal pannicular infiltration by atypical lymphocytes. The cutaneous lymphocytic infiltrate was composed of a monoclonal population of B cells with lambda light chains. Atypical lymphocytes were also seen in the peripheral blood, and flow cytometry showed a predominance of the same phenotype of B cells with lambda light chains. Chemotherapy for systemic B-cell lymphoma resulted in the simultaneous resolution of EN and the lymphoma. This is the first documentation of EN representing direct cutaneous invasion by a B-cell lymphoma.

Histochemical Evaluation of Glycosaminoglycan Deposition in the Skin

Histologic demonstration of glycosaminoglycan (GAG) deposition in the skin has been based on the use of either colloidal iron or alcian blue. To define the best technique for the determination of skin GAG content we undertook a prospective study comparing the two stains and evaluating the use of cetylpyridinium chloride (CPC) to enhance fixation. Slides were prepared from skin biopsies obtained from five patients with cutaneous mucinoses. The preparations were coded and examined by three observers. Colloidal iron staining gave a higher intensity for GAG deposits in papillary and reticular dermis. Digestion by specific enzymes identified similar GAGs with either colloidal iron, or alcian blue; however, colloidal iron made GAGs more obvious, partly due to the contrast afforded by the yellow background stain. The addition of CPC to the fixative appreciably enhanced GAG fixation without interfering with the action of enzymes. Experimentally, we confirmed this effect of CPC by determining a pronounced decrease in GAG leakage into the fixative from CPC treated human umbilical cord. We conclude that the combination of CPC fixation and colloidal iron staining gives the best definition of skin GAGs in clinical specimens.

Graft versus host disease.

Graft versus host disease (GVHD) occurs in 50% to 70% of patients receiving bone marrow transplants. It can also develop in immunosuppressed patients with malignancies who receive nonirradiated blood transfusions. Most work indicates that the primary mechanism of GVHD is cell-mediated. It is likely that humoral factors are involved as well. Cutaneous manifestations are the earliest and most frequent sign of the disease. These may be morbilliform, scarlantiniform, lichenoid, or sclerodermoid lesions. In acute GVHD, the skin, gastrointestinal tract, and liver are commonly affected. In chronic GVHD, findings similar to collagen vascular disorders are present. A skin biopsy establishes the diagnosis.

Antibodies against the insulin receptor in paraneoplastic acanthosis nigricans

Acanthosis nigricans is a skin disorder associated with endocrine abnormalities, autoimmune disease, and systemic malignancies. Insulin resistance is a common accompaniment of the nonmalignant varieties of acanthosis nigricans. A 44-year-old man is described with a functioning metastatic pheochromocytoma, acanthosis nigricans, and insulin-resistant diabetes mellitus. Studies of insulin action showed a low titer of anti-insulin antibodies and a very high titer of antibodies against the insulin receptor. This case documents for the first time insulin resistance due to anti-insulin receptor antibodies in a paraneoplastic variety of acanthosis nigricans.