HOXD10 M319K mutation in a family with isolated congenital vertical talus.

Congenital vertical talus (CVT) is a primary dislocation of the talonavicular joint that often occurs in neuromusculoskeletal syndromes, but may also be seen as an isolated abnormality. Six families with isolated CVT were ascertained. DNA was isolated from 21 affected individuals and 17 unaffected individuals from these families, as well as from five sporadic patients with CVT.

Structural abnormalities of the cornea and lid resulting from collagen V mutations.

Purpose: Type V collagen forms heterotypic fibrils with type I collagen and accounts for 10% to 20% of corneal collagen. The purpose of this study was to define the ocular phenotype resulting from mutations in the type V collagen genes COL5A1 and COL5A2 and to study the pathogenesis of anomalies in a Col5a1-deficient mouse.

Methods: Seven patients with classic Ehlers-Danlos syndrome (EDS) due to COL5A1 haploinsufficiency and one with an exon-skipping mutation in COL5A2 underwent an ocular examination, corneal topography, pachymetry, and specular microscopy.

Myogenic regulation of arterial diameter: role of potassium channels with a focus on delayed rectifier potassium current.

The phenomenon of myogenic constriction of arterial resistance vessels in response to increased intraluminal pressure has been known for over 100 years, yet our understanding of the molecular mechanisms involved remains incomplete. The focus of this paper concerns the potassium (K+) channels that provide a negative feedback control of the myogenic depolarization of vascular smooth muscle cells that is provoked by elevations in intraluminal pressure, and specifically, the contribution of delayed rectifier (KDR) channels. Our knowledge of the important role played by KDR channels, as well as their molecular identity and acute modulation via changes in gating, has increased dramatically in recent years.

Multiple epiphyseal dysplasia mutations in MATN3 cause misfolding of the A-domain and prevent secretion of mutant matrilin-3.

Multiple epiphyseal dysplasia (MED) is a relatively common skeletal dysplasia that can present in childhood with a variable phenotype of short stature and pain and stiffness in the large joints, and often progresses to early-onset osteoarthritis in adulthood. Mutations in the matrilin-3 gene (MATN3) have recently been shown to underlie some forms of autosomal dominant MED. To date all MED mutations in matrilin-3 cluster in the single A-domain, suggesting that they may disrupt the structure and/or function of this important domain.

Schmid type of metaphyseal chondrodysplasia and COL10A1 mutations--findings in 10 patients.

The Schmid type of metaphyseal chondrodyplasia (MCDS) is characterized by short stature, widened growth plates, and bowing of the long bones. It results from autosomal dominant mutations of COL10A1, the gene which encodes alpha1(X) chains of type X collagen. We report the clinical and radiographic findings in 10 patients with MCDS and COL10A1 mutations.

Differentiation-induced loss of heparan sulfate in human exostosis derived chondrocytes.

An exostosis or osteochondroma is an aberrant bony growth occurring next to the growth plate either as an isolated growth abnormality or as part of the Hereditary Multiple Exostosis (HME) syndrome. Mutations in either exostosin 1 (EXT1) or exostosin 2 (EXT2) gene cause the HME syndrome and also some isolated osteochondromas. The EXT1 and EXT2 genes are glycosyltransferases that function as hetero-oligomers in the Golgi to add repeating glycosaminoglycans (GAGs) to heparan sulfate (HS) chains.

Botany: specialized bird perch aids cross-pollination.

Birds may hover over or perch on flowers when feeding on nectar, and this assists cross-pollination if they then visit other plants. Here we investigate the curious sterile inflorescence axis of the South African Cape endemic 'rat's tail' plant (Babiana ringens, Iridaceae), whose function--unlike in other bird-pollinated plants--is exclusively to provide a perch for foraging birds. We find that this structure promotes the plant's mating success by causing the malachite sunbird (Nectarinia famosa), its main pollinator, to adopt a position ideal for the cross-pollination of its unusual ground-level flowers.

A novel COL1A1 mutation in infantile cortical hyperostosis (Caffey disease) expands the spectrum of collagen-related disorders.

Infantile cortical hyperostosis (Caffey disease) is characterized by spontaneous episodes of subperiosteal new bone formation along 1 or more bones commencing within the first 5 months of life. A genome-wide screen for genetic linkage in a large family with an autosomal dominant form of Caffey disease (ADC) revealed a locus on chromosome 17q21 (LOD score, 6.78).

Preferences for life-sustaining treatments in advance care planning and surrogate decision making.

Background: Surrogates and clinicians often make treatment decisions for decisionally incapacitated patients with limited knowledge of their preferences. This study examined patients' life-sustaining treatment preferences to facilitate advance care planning discussions and surrogate decision making.

Methods: We interviewed 342 participants from 7 groups: younger and older well adults; persons with chronic illness, terminal cancer, and acquired immunodeficiency syndrome (AIDS); stroke survivors; and nursing home residents.

Congenital dislocation of the patella.

Objective: Our objective was to present the imaging findings for congenital dislocation of the patella, an uncommon condition with variable clinical manifestations in patients of different ages.

Conclusion: Sonography can clearly illustrate the presence and location of the laterally displaced patella and the anatomy of adjacent joint structures. The high resolution for soft-tissue, cartilaginous, and bony structures of the immature skeleton makes sonography a valuable tool in the management of congenital dislocation of the patella.

Heterozygous mutations in the LDL receptor-related protein 5 (LRP5) gene are associated with primary osteoporosis in children.

Unlabelled: Three of 20 patients with juvenile osteoporosis were found to have a heterozygous mutation in the LRP5 gene. No mutations were found in the type I collagen genes. Mutations in the other family members with similar bone phenotype confirmed that LRP5 has a role in both juvenile and adult osteoporosis.

Improvements in advance care planning in the Veterans Affairs System: results of a multifaceted intervention.

Background: Advance care planning (ACP) aims to guide health care in the event of decisional incapacity. Interventions to promote ACP have had limited effectiveness. We conducted an educational and motivational intervention in Department of Veterans Affairs outpatient clinics to increase ACP use and proxy and health care provider understanding of patients' preferences and values.

Radiographic vertebral morphology: a diagnostic tool in pediatric osteoporosis.

Objective: To assess the value of spinal radiographs in determining the significance of reductions in bone mass or density in chronically ill children.

Study Design: A pediatric scoring method for assessment of osteoporotic vertebral changes, developed on the basis of radiographs of 70 healthy controls and established adult scoring methods, was subsequently used to assess 32 pediatric patients with suspected secondary osteoporosis. Radiographic findings were correlated with bone mineral density (BMD), clinical data, and biochemistry.

Predicting mating patterns from pollination syndromes: the case of "sapromyiophily" in Tacca chantrieri (Taccaceae).

Tacca, a genus of tropical herbs, possesses near black flowers, conspicuous involucral bracts and whisker-like filiform bracteoles. These features have been assumed to function as a "deceit syndrome" in which reproductive structures resemble decaying organic material attracting flies that facilitate cross-pollination (sapromyiophily). We investigated pollination and mating in Tacca chantrieri populations from SW China to evaluate this assumption.

COMP mutations, chondrocyte function and cartilage matrix.

Cartilage oligomeric matrix protein (COMP) is a large extracellular pentameric glycoprotein found in the territorial matrix surrounding chondrocytes. More than 60 unique COMP mutations have been identified as causing two skeletal dysplasias, pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED/EDM1). Recent studies demonstrate that calcium-binding and calcium induced protein folding differ between wild type and mutant COMP proteins and abnormal processing of the mutant COMP protein causes the characteristic large lamellar appearing rough endoplasimic reticulum (rER) cisternae phenotype observed in PSACH and EDMI growth plate chondrocytes.

Heteromultimeric Kv1 channels contribute to myogenic control of arterial diameter.

Inhibition of vascular smooth muscle (VSM) delayed rectifier K+ channels (K(DR)) by 4-aminopyridine (4-AP; 200 micromol/L) or correolide (1 micromol/L), a selective inhibitor of Kv1 channels, enhanced myogenic contraction of rat mesenteric arteries (RMAs) in response to increases in intraluminal pressure. The molecular identity of K(DR) of RMA myocytes was characterized using RT-PCR, real-time PCR, and immunocytochemistry. Transcripts encoding the pore-forming Kvalpha subunits, Kv1.

Cell-type specific trafficking of expressed mutant COMP in a cell culture model for PSACH.

Pseudoachondroplasia (PSACH) is an autosomal dominant disease that mainly affects cartilage, resulting in skeletal dysplasias and early onset osteoarthritis. PSACH is caused by mutations in the cartilage oligomeric matrix protein (COMP) gene. PSACH chondrocytes accumulate unique COMP-containing lamellar structures in an expanded rough endoplasmic reticulum (rER).

Mutations in the known genes are not the major cause of MED; distinctive phenotypic entities among patients with no identified mutations.

Multiple epiphyseal dysplasia (MED) is a clinically and genetically heterogeneous chondrodysplasia. Mutations in six genes (COMP, COL9A1, COL9A2, COL9A3, MATN3 and DTDST) have been reported, but the genotype-phenotype correlations and the proportions of cases due to mutations in these genes are still not well characterized. We performed a clinical, radiological and molecular analysis of known MED genes on 29 consecutive MED patients.

Imatinib mesylate: an attractive alternative in young children with large, surgically challenging dermatofibrosarcoma protuberans.

To document the clinical activity of imatinib mesyalte in a child with a dermatofibrosarcoma protuberans (DFSP). An 18-month-old girl presented with a large extremity DFSP. As surgical resection would have caused unacceptable functional defects, imatinib mesylate was administered to induce tumor reduction and or stabilization.

Impairment and activity limitation associated with epiphyseal dysplasia in children.

Objectives: To develop a profile of impairment and activity limitation among children with epiphyseal dysplasia (ED) and to identify the relationship between these 2 domains.

Design: Cross-sectional study.

Setting: Acute, pediatric academic and health sciences center.