Expression of the ryanodine receptor isoforms in immune cells.

Ryanodine receptor (RYR) is a Ca(2+) channel that mediates Ca(2+) release from intracellular stores. We have used RT-PCR analysis and examined its expression in primary peripheral mononuclear cells (PBMCs) and in 164 hemopoietic cell lines. In PBMCs, type 1 RYR (RYR1) was expressed in CD19(+) B lymphocytes, but less frequently in CD3(+) T lymphocytes and in CD14(+) monocytes. Type 2 RYR (RYR2) was mainly detected in CD3(+) T cells. Induction of RYR1 and/or RYR2 mRNA was found after treatment with stromal cell-derived factor 1, macrophage-inflammatory protein-1alpha (MIP1alpha) or TGF-beta. Type 3 RYR (RYR3) was not detected in PBMCs. Many hemopoietic cell lines expressed not only RYR1 or RYR2 but also RYR3. The expression of the isoforms was not associated with specific cell lineage. We showed that the RYR-stimulating agent 4-chloro-m-cresol (4CmC) induced Ca(2+) release and thereby confirmed functional expression of the RYR in the cell lines expressing RYR mRNA. Moreover, concordant induction of RYR mRNA with Ca(2+) channel function was found in Jurkat T cells. In untreated Jurkat T cells, 4CmC (>1 mM) had no effect on Ca(2+) release, whereas 4CmC (<400 microM) caused Ca(2+) release after the induction of RYR2 and RYR3 that occurred after treatment with stromal cell-derived factor 1, macrophage-inflammatory protein-1alpha, or TGF-beta. Our results demonstrate expression of all three isoforms of RYR mRNA in hemopoietic cells. Induction of RYRs in response to chemokines and TGF-beta suggests roles in regulating Ca(2+)-mediated cellular responses during the immune response.

North American malignant hyperthermia population: screening of the ryanodine receptor gene and identification of novel mutations.

BACKGROUND: Malignant hyperthermia (MH) is a disorder of skeletal muscle manifested as a life-threatening hypermetabolic crisis in susceptible individuals after exposure to inhalational anesthetics and depolarizing muscle relaxants. Mutations in the gene encoding the skeletal muscle ryanodine receptor (RYR1) are considered a common cause of the disorder, and, to date, more than 20 RYR1 mutations have been reported in European and Canadian families. Some studies suggest that differences may exist in the frequencies and distribution of mutations in the RYR1 gene between European and North American MH families the frequency and distribution of mutations in the RYR1 gene. METHODS: Skeletal muscle samples from 73 unrelated individuals diagnosed as MH susceptible according to the North American MH caffeine-halothane contracture test were studied. Genomic DNA of MH-susceptible patients was investigated by polymerase chain reaction-based restriction fragment length polymorphism, single-strand conformation polymorphism, and sequencing analysis. The majority of known RYR1 mutations were analyzed using the restriction fragment length polymorphism method, whereas new mutations were searched by single-strand conformation polymorphism in exons 12, 15, 39, 40, 44, 45, and 46 of the gene. RESULTS: Seven known RYR1 mutations (Arg163Cys, Gly248Arg, Arg614Cys, Val2168Met, Thr2206Met, Gly2434Arg, and Arg2454His) were detected at frequencies of 2.7, 1.4, 1.4, 1.4, 1.4, 5.5, and 4.1%, respectively. In addition, three novel amino acid substitutions (Val2214Ile, Ala2367Thr, and Asp2431Asn) were detected at frequency of 1.4% each. These 10 mutations account for 21.9% of the North American MH-susceptible population. CONCLUSION: Three novel candidate mutations in the RYR1 gene were identified in these MH patients. The frequency and distribution of RYR1 mutations observed in this North American MH population was markedly different from that previously identified in Europe. Larger-scale studies are necessary to clarify the type and frequency of mutations in RYR1 associated with MH in North American families.

Dermal contact dermatitis to a disposable electrode plate.

A 50-year-old man developed a dermal type of allergic contact dermatitis after exposure to a disposable electrosurgical electrode. Patch testing did not determine the allergenic component, but the electrode contained none of the substances known to cause dermal contact dermatitis.

Transient neonatal pustular melanosis.

A black male infant had congenital lesions that consisted of pigmented macules, many of which had a peripheral collarette of scale, and vesicopustules. The appearance of this patient fit the clinical syndrome of transient neonatal pustular melanosis, a newly described vesicopustular disease of the newborn. Differential diagnosis in this patient included the following conditions: erythema toxicum neonatorum, staphylococcal pyoderma, and herpes simplex.

Alkaptonuria with extensive ochronosis.

A 59-year-old woman with previously documented alkaptonuria was examined for extensive ochronosis of recent onset. The cause of the extensive skin pigmentations were thought to be secondary to decreased renal clearance of homogentisic acid because of a decline in the patient's renal function. If extensive or rapidly progressive skin pigmentation is noted in a patient with alkaptonuria, then evaluation of the patient's renal status should be done because unrelated renal disease has been reported in patients with severe ochronosis.

The diagonal earlobe crease: a cutaneous manifestation of coronary artery disease.

Skin signs of systemic disease are of great interest to dermatologists. Reports based on coronary angiographic studies and postmortem examinations have shown that there is a higher prevalence of earlobe creases in patients with coronary heart disease. In this report seven patients with documented coronary heart disease are presented. Five of the seven patients had bilateral diagonal ear creases. The evidence to date indicates that this ear crease may be a cutaneous sign of coronary heart disease, and can therefore be used to identify patients at an increased risk for coronary heart disease.

Cutaneous manifestations of Noonan's syndrome.

Noonan's syndrome is a multisystem syndrome that has received little attention in the dermatologic literature, although there are numerous cutaneous manifestations that have been described. A typical case of Noonan's syndrome is presented. Clinical findings in this patient included short stature, curly scalp hair, prominent ears, hypertelorism, webbing of the neck, cubitus valgus, pigmented nevi, stasis dermatitis, and plantar hyperkeratosis. The latter two findings have not been previously reported in Noonan's syndrome. We urge that dermatologists become more aware of this syndrome to document the spectrum of changes that may occur in Noonan's syndrome.

Clinical syndrome of chemotaxis defect, infections, and hyperimmunoglobulinemia E. A case report.

A 17-year-old girl had a clinical syndrome that consisted of neutrophil chemotaxis defect, recurrent bacterial infections, and hyperimmunoglobulinemia E. Neutrophil chemotaxis was quantitated by a radioassay technique that used 51Cr-labeled neutrophils and a double micropore filter chemotaxis chamber. A table of the features of other cases of this syndrome is presented. Since ten of the 13 patients who are described had a chronic eczematoid dermatitis, we suggest that this may be a fourth feature of this syndrome. Red hair and fair skin were not consistent findings in these patients. In the evaluation of patients with chronic, recurrent bacterial infections of the skin of undetermined origin, we recommend determination of serum IgE levels. If IgE is found to be elevated, one should consider the presence of this syndrome, and neutrophil chemotaxis should then be examined.

Extirpation of warts by a loop electrode and cutting current.

Warts are a common dermatologic problem. Electrodesiccation has been the recommended surgical approach for therapy. An alternate method utilizing a wire loop electrode and cutting current is presented. The authors feel it is the surgical treatment of choice for most warts.