Pachyonychia congenita tarda.

A 42-year-old man presented with painful toenails which were overcurved transversely and onycholytic. Examination revealed that all toenails, the thumbs and index fingers were similarly affected. In addition, he had a small area of leukokeratosis in the mouth, epidermal cysts of the scrotal skin and a small area of hyperkeratosis on the ulnar borders of his hands. His characteristic nail changes began in the great toenails at the age of 20 years. After renal transplantation at age 39, the other nails changed and he developed the features described above. His sister has overcurvature of the fifth toenails. A diagnosis of pachyonychia congenita tarda was made. His case is compared with 14 other reported cases of this rare syndrome.

Involvement of the small GTPases XRhoA and XRnd1 in cell adhesion and head formation in early Xenopus development.

The Rho family of small GTPases regulates a variety of cellular functions, including the dynamics of the actin cytoskeleton, cell adhesion, transcription, cell growth and membrane trafficking. We have isolated the first Xenopus homologs of the Rho-like GTPases RhoA and Rnd1 and examined their potential roles in early Xenopus development. We found that Xenopus Rnd1 (XRnd1) is expressed in tissues undergoing extensive morphogenetic changes, such as marginal zone cells involuting through the blastopore, somitogenic mesoderm during somite formation and neural crest cells. XRnd1 also causes a severe loss of cell adhesion in overexpression experiments. These data and the expression pattern suggest that XRnd1 regulates morphogenetic movements by modulating cell adhesion in early embryos. Xenopus RhoA (XRhoA) is a potential XRnd1 antagonist, since overexpression of XRhoA increases cell adhesion in the embryo and reverses the disruption of cell adhesion caused by XRnd1. In addition to the potential roles of XRnd1 and XRhoA in the regulation of cell adhesion, we find a role for XRhoA in axis formation. When coinjected with dominant-negative BMP receptor (tBR) in the ventral side of the embryo, XRhoA causes the formation of head structures resembling the phenotype seen after coinjection of wnt inhibitors with dominant-negative BMP receptor. Since dominant-negative XRhoA is able to reduce the formation of head structures, we propose that XRhoA activity is essential for head formation. Thus, XRhoA may have a dual role in the embryo by regulating cell adhesion properties and pattern formation.

Carney complex: in a patient with multiple blue naevi and lentigines, suspect cardiac myxoma.

Carney complex is characterized by spotty pigmentation (blue naevi and lentigines), myxomas (cardiac, cutaneous, mammary), endocrine over-activity (Cushing's syndrome, acromegaly), testicular tumours, and schwannomas. We report a male with multiple blue naevi, lentigines, testicular large cell calcifying Sertoli-cell tumour and four cardiac myxomas. The myxomas caused two cerebrovascular accidents and a myocardial infarction. All patients with multiple blue naevi or lentigines should be investigated for the life-threatening association of cardiac myxomas.

Vitamin A deficiency phrynoderma: due to malabsorption and inadequate diet.

We describe a patient with vitamin A deficiency phrynoderma caused by a combination of inadequate dietary intake of vitamin A and beta-carotene and malabsorption secondary to primary visceral myopathy and total colectomy.

Radiation-induced localized scleroderma in breast cancer patients.

Radiation-induced scleroderma in breast cancer patients appears to occur in approximately one out of every 500 patients. We report four cases that developed within 3 months of conservative breast surgery and postoperative radiation treatment. The reaction was contained entirely within the treatment field and demonstrated the typical features of this condition where the breast becomes erythematous, violaceous, indurated, retracted, and progressively pigmented. The breast tends to soften and become more comfortable over 1-4 years; however, significant induration, retraction and pigmentary changes remain. There appears to be no predictive factors. Radiation-induced scleroderma must be differentiated from cellulitis and recurrent breast cancer.

IgA multiple myeloma presenting as an acquired bullous disorder.

A 63-year-old man presented with an intensely pruritic vesiculo-bullous eruption on the limbs and was subsequently found to have an IgA kappa multiple myeloma. The eruption clinically and histologically was suggestive of linear IgA disease (LAD), dermatitis herpetiformis (DH), epidermolysis bullosa acquisita (EBA), or bullous lupus erythematosus (LE), with the skin biopsy revealing subepidermal bullae and dermal papillary micro-abscesses. However, direct immunofluorescence showed a unique pattern of diffuse dermal IgA staining. Although chemotherapy produced a dramatic resolution of the lesions, which paralleled the fall in serum IgA paraprotein level, the myeloma later became progressive and the resulting paraprotein increase was accompanied by recurrence of the eruption. We propose that this patient's rash was the presenting manifestation of his multiple myeloma, and was a consequence of transudation of IgA paraprotein into the dermis.

Disruption of BMP signals in embryonic Xenopus ectoderm leads to direct neural induction.

Bone morphogenetic proteins (BMPs), which have been implicated in the patterning of mesoderm, are members of the transforming growth factor-beta (TGF-beta) superfamily. We have investigated the roles of Xenopus BMP-7 (XBMP-7) and BMP-4 (XBMP-4), and activin (another TGF-beta-related molecule) in early development by generating dominant-negative versions of these growth factors. Mutations were generated by altering the cleavage sites that are required for maturation of the active dimeric forms of XBMP-7, XBMP-4, and activin. These mutant constructs, designated Cm-XBMP-7, Cm-XBMP-4, and Cm-activin, result in polypeptides that allow for dimerization of the subunits, but are incapable of maturation. Expression of Cm-XBMP-7 and Cm-XBMP-4, but not Cm-activin, in the ventral marginal zone of the Xenopus embryo results in the development of a secondary axis, similar to that seen by ectopic expression of the truncated BMP receptor. These results suggest that the cleavage mutants interfere with BMP signaling during mesodermal patterning. We also found that expression of Cm-XBMP-7 or Cm-XBMP-4 in animal cap ectoderm directly induces neuroectoderm. The neural induction was specific for Cm-XBMP-7 and Cm-XBMP-4 because ectopic expression of Cm-activin or Vg-1 did not mimic the same phenotype. Molecular study of neural patterning by Cm-XBMP-7 and Cm-XBMP-4 revealed that only anterior neuroectodermal markers are expressed in response to these Cm-XBMPs. These results suggest that the BMPs are involved in the specification of ectoderm in Xenopus development, and that neural induction requires the removal of BMP signals in the ectoderm. We propose that neural induction occurs by a default mechanism, whereby the inhibition of BMP signaling is required for the conversion of ectoderm to neuroectoderm in the developing Xenopus embryo.

Histologic changes in Paget's disease treated with calcitonin.

In recent years the use of calcitonin in the medical treatment of Paget's disease of bone has been gaining in popularity. Seventeen patients on long term calcitonin therapy showed objective morphologic evidence of improvement in the quality of bone matrix deposition, in the trabecular organization, and in the parameters used to evaluate the rates of bone turnover. The usefulness of bone biopsy and fine detail radiography of the biopsy core in evaluating the progress of disease and the effects of therapy is discussed. It is concluded that the longer the period of therapy and follow-up, the higher the proportion of patients showing histologic evidence of improvement.