Carmen G. Espinoza

Biochemical composition of adult human lung surfactant.

Surfactant was isolated from minced adult human lung tissues by repetitive centrifugation on NaBr density gradients. The surface active fraction contained 12 mg phospholipid per mg of protein. Eighty percent of the phospholipid was phosphatidylcholine and 9% was phosphatidylglycerol. The phosphatidylcholines, 55% of which were disaturated, contained more than 70% palmitic acid. In contrast, phosphatidylglycerol contained 22% palmitic acid and 52% oleic acid, suggesting that the importance of phosphatidylglycerol in surfactant function relates to its acidic head group. The most abundant proteins in human surfactant were high molecular weight (>400,000) glycoproteins which on reduction with dithiothreitol yielded peptides of 34,000 daltons. Antibodies to the high molecular weight proteins were prepared in rabbits and using immunoperoxidase methods were shown to stain alveolar type II cells and the alveolar and bronchial surfaces, but no other human tissues. A low molecular weight protein was also present in lung surfactant and was most apparent in surfactant subfractions which had higher phospholipid to protein ratios. The results of this study provide a basis to further investigate the role of normal and altered surfactant constituents in disease states of the human lung.

Biologic Therapy(TNF-α Antagonists)-Induced Psoriasis: A Cytokine Imbalance Between TNF-α and IFN-α?

We report 3 patients with psoriatic arthritis and 2 with rheumatoid arthritis who developed worsening, and/or de novo psoriasis, and/or psoriasiform rash, while on tumor necrosis factor antagonist therapy. All 5 patients initially presented with active skin, and/or joint inflammatory involvement, and exhibited significant clinical response to tumor necrosis factor antagonist therapy. Within approximately 6 months, however, psoriatic and/or psoriasiform rash developed de novo in 2 rheumatoid arthritis patient and exacerbated in the other 3 patients. Biopsy findings revealed histologic and immunohistochemical changes indistinguishable from psoriasis.Psoriatic rash improved after discontinuation of biologic therapy and/or initiation of a short course of oral prednisone. One patient with psoriatic arthritis was rechallenged with infliximab due to exacerbation of both psoriasis and psoriatic arthritis, and this was followed by prompt improvement of both conditions. At 6 months follow-up, this patient remains under excellent control. To date, there have been over 50 cases of this type of dermatologic complication described. Interferon alpha seems to play an important role in the pathogenesis of this complication. This type of complication has been described with all 3 available tumor necrosis factor inhibitors, and most patients improve after discontinuation of biologic therapy.

Dowling-Degos disease, hidradenitis suppurativa, and multiple keratoacanthomas

We report a case in which one patient had Dowling-Degos disease (reticulate pigmented anomaly of the flexures), hidradenitis suppurativa, and multiple keratoacanthomas. Abnormal epithelial proliferation involving mainly the pilosebaceous apparatus has been recognized in all three conditions. We speculate that a single underlying defect in follicular epithelial proliferation, characterized by variable expressivity, accounts for the coexistence of these clinically distinct disorders of follicular derivation.

Oral methotrexate therapy for chronic rheumatoid arthritis ulcerations

Eight patients with long-standing rheumatoid arthritis and cutaneous vasculitis ulcerations resistant to conventional therapy were treated successfully with a low-dose intermittent regimen of oral methotrexate. Objective clinical response was prompt and complete resolution was observed at about 12 weeks of therapy. The drug was well tolerated. Mild gastrointestinal side effects were the most common untoward reaction. We conclude that methotrexate therapy is an effective agent for some of the extraarticular manifestations of rheumatoid arthritis including vasculitis, and further clinical evaluation should be a consideration.

Sipple syndrome with lichen amyloidosis as a paracrinopathy: Pleiotropy, heterogeneity, or a contiguous gene?

A five-generation white family with multiple endocrine neoplasia type 2A had six affected members. Two, a mother and her daughter, had interscapular cutaneous pruritic lesions resembling macular/lichen amyloidosis. In the daughter, light microscopy showed homogeneous aggregates in the papillary dermis. Crystal violet staining showed metachromasia and indicated that the deposits were amyloid. This is the fourth family with familial medullary thyroid carcinoma with cutaneous amyloidosis and as such it allowed comparative analysis. Genetic heterogeneity, a contiguous gene, and pleiotropy were considered. It appears that multiple endocrine neoplasia type 2A/familial medullary thyroid carcinoma with cutaneous amyloidosis represents the phenotypic variability of the expression of a pleiotropic gene. The condition is one of the predominantly ectodermal autosomal dominant phakomatoses and is most likely a paracrinopathy.

Ultrastructural and immunohistochemical studies of bronchiolo‐alveolar carcinoma

A detailed ultrastructural study was made of seven cases of bronchiolo‐alveolar carcinoma, and the findings were correlated with histochemical and immunohistochemical data. By electron microscopic examination all seven tumors displayed glandular differentiation, manifested by the presence of microvilli and intercellular junctions, with or without mucin production. Variable proportions of tumor cells retained ultrastructural characteristics of alveolar type II cells and Clara cells. In addition, some tumor cells revealed desmosomes and tonofilaments consistent with squamous differentiation. Immunohistochemical evaluation was carried out using a peroxidase—antiperoxidase technique and specific antibodies against surfactant high molecular weight glycoproteins, keratin proteins, IgA + secretory piece, carcinoembryonic antigen (CEA), human chorionic gonadotropin (HCG), and alpha‐fetoprotein (AFP). Four tumors with type II cell‐like differentiation stained with anti‐surfactant glycoprotein sera. All seven tumors stained focally with anti‐keratin and IgA + anti‐surfactant piece antibodies, and diffusely with CEA. These tumors failed to stain with antisera against HCG and AFP. It is concluded that bronciolo‐alveolar carcinomas are primarily composed of cells with alveolar and bronchiolar cell differentiation. Adequate criteria were established for ultrastructural identification of tumor cells with differentiation to type II alveolar cell or Clara cell. Moreover, the findings of this study indicate that the surfactant glycoprotein marker, when present in a given tumor either diffusely or focally, is diagnostic of bronchiolo‐alveolar carcinoma.

Lymphomatoid papulosis: A premalignant T cell disorder

In an attempt to better define the process of lymphomatoid papulosis, two cases were studied by means of light and electron microscopy, immunohistochemistry studies, including the use of monoclonal antibodies, and cytogenetic technics. About 90% of the dermal lymphoid infiltrate, including the atypical cells, reacted with antibodies that define helper-inducer T cells. Only a few cells, about 5%, reacted with antibodies that define cytotoxic-suppressor T cells. Langerhans cells were increased mostly within the epidermis, and in the dermis they were in close proximity to lymphoid cells. Cytogenetic studies disclosed an abnormal hypertetraploid karyotype in dividing cells from the skin lesion, whereas skin fibroblast and phytohemagglutinin-stimulated cells from peripheral blood cultures had a diploid karyotype. The results support the concept that lymphomatoid papulosis is a disorder characterized by a predominance of helper-inducer T cells, including the atypical cells bearing an abnormal karyotype.

An animal model of abdominal aortic aneurysm created with peritoneal patch: technique and initial results.

AbstractThe purpose of this study was to develop an abdominal aortic aneurysm model that more closely resembles the morphology of human aneurysms with potential for further growth of the sac. An infrarenal abdominal aortic aneurysm (AAA) model was created with a double-layered peritoneal patch in 27 domestic swine. The patch, measuring in average from 6 to 12 cm in length and from 2 to 3 cm in width, was sutured to the edge of an aortotomy. Pre- and postsurgical digital subtraction aortograms (DSA) were obtained to document the appearance and dimensions of the aneurysm. All animals were followed with DSA for up to 5 months. Laparoscopic examination enhanced by the use of laparoscopic ultrasound was also carried out in 2 animals to assess the aneurysm at 30 and 60 days following surgery. Histological examination was performed on 4 animals. All the animals that underwent the surgical creation of the AAA survived the surgical procedure. Postsurgical DSA demonstrated the presence of the AAA in all animals, defined as more than 50% increase in diameter. The aneurysmal mean diameter increased from the baseline of 10.27 ± 1.24 to 16.69 ± 2.29 mm immediately after surgery, to 27.6 ± 6.59 mm at 14 days, 32.45 ± 8.76 mm at 30 days (p < 0.01), and subsequently decreased to 25.98 ± 3.75 mm at 60 days. A total of 15 animals died of aneurysmal rupture that occurred more frequently in the long aneurysms (≥6 cm in length) than the short aneurysms (<6 cm in length) during the first 2 weeks after surgery (p < 0.05). No rupture occurred beyond 16 days after surgery. Four animals survived and underwent 60-day angiographic follow-up. Laparoscopic follow-up showed strong pulses, a reddish external appearance and undetectable suture lines on the aneurysmal wall. On pathology, the patches were well incorporated into the aortic wall, the luminal wall appeared almost completely endothelialized, and cellular and matrix proliferation were noted in the aneurysmal wall. A reproducible technique for the creation of an infrarenal AAA model was developed using a peritoneal patch in swine. The aneurysm model proved to have potential for further growth of the sac and a tendency to rupture. Because of the growth potential, this might be a better model than those with a noncompliant aneurysmal wall for the preclinical evaluation of stent-graft devices.

Epidermolysis bullosa acquisita. Direct immunofluorescence and ultrastructural studies

A case of epidermolysis bullosa acquisita (EBA), associated with inflammatory bowel disease in which cicatricial alopecia was present, was studied by electron microscopy and direct immunofluorescence microscopy. Direct immunofluorescence studies were performed on both clinically normal and perilesional skin, with and without previous separation of the epidermis from the dermis by incubation with 1 M sodium chloride. We propose the use of this separation technique to identify the level of antibody deposition in patients with EBA in whom circulating antibodies are lacking. This technique may be particularly beneficial in delineating between EBA and the clinically similar scarring localized forms of bullous pemphigoid in which circulating antibodies are often absent.

HYPOPIGMENTED MACULES IN ACANTHOLYTIC DISORDERS

Background. Widespread hypopigmented macules are rarely seen in heavily pigmented patients with Dariers disease. Previous hypotheses concerning the cause of decreased pigmentation suggest it is a postinflammatory phenomenon or that the hypomelanosis is evidence of sub‐clinical acantholysis.