Determination of the calcium binding capacity to discriminate between urines of calcium stone formers and healthy persons

Summary Calcium binding by undiluted fasting urine has been tested as a means of demonstrating the capacity of urine from control subjects and calcium stone patients to hold spontaneous precipitation of stone forming compounds. Preliminary data are promising with respect to the possibility that controls and patients can be separated.     

Surgical management of congenital lobar emphysema

Here in nine patients with congenital lobar emphysema who had been treated surgically in the previous 10 years are reported. The ages of the patients at diagnosis ranged from 26 days to 11 months. The six patients whose symptoms started in the neonatal period had more severe dyspnea, cyanosis and respiratory distress. Tube thoracostomy was performed in two of three patients who had been misdiagnosed initially. The affected side was the left upper lobe in five patients, the right upper lobe in three, and the right middle and upper lobes in one patient. Lobectomy was performed in all cases. Dysplasia of the bronchial cartilage was found in six patients and bronchial atresia of the left upper lobe was found in another infant as the etiologic cause of the condition. Although the possibility of conservative management in congenital lobar emphysema has been reported recently, we believe that surgery is the treatment of choice in patients who have persistent or progressive, severe respiratory distress in spite of medical treatment.     

Phenotypic suppression of acral peeling skin syndrome in a patient with autosomal recessive congenital ichthyosis

Autosomal recessive congenital ichthyosis (ARCI) manifests with generalized scaling often associated with generalized erythema. Mutations in at least 13 different genes have been reported to cause ARCI. Acral peeling skin syndrome (APSS) is a rare autosomal recessive disorder manifesting with peeling over the distal limbs and dorsal surfaces of hands and feet. APSS is mostly due to mutations in TGM5, encoding transglutaminase 5. Both ARCI and APSS are fully penetrant genetic traits. Here, we describe a consanguineous family in which one patient with mild ARCI was found to carry a homozygous mutation in ALOXE3 (c.1238G > A; p.Gly413Asp). The patient was also found to carry a known pathogenic homozygous mutation in TGM5 (c.1335G > C; p.Lys445Asn) but did not display acral peeling skin. Her uncle carried the same homozygous mutation in TGM5 but carried the ALOXE3 mutation in a heterozygous state and showed clinical features typical of APSS. Taken collectively, these observations suggested that the ALOXE3 mutation suppresses the clinical expression of the TGM5 variant. We hypothesized that ALOXE3 deficiency may affect the expression of a protein capable of compensating for the lack of TGM5 expression. Downregulation of ALOXE3 in primary human keratinocytes resulted in increased levels of corneodesmosin, which plays a critical role in the maintenance of cell-cell adhesion in the upper epidermal layers. Accordingly, ectopic corneodesmosin expression rescued the cell-cell adhesion defect caused by TGM5 deficiency in keratinocytes as ascertained by the dispase dissociation assay. The present data thus provide evidence for phenotypic suppression in a human hereditary skin disorder.     

Recessive epidermolytic ichthyosis results from loss of keratin 10 expression,regardless of the mutation location

Epidermolytic ichthyosis (EI) is a rare skin disorder caused by mutations in the genes KRT1 and KRT10, and is usually inherited in an autosomal dominant fashion. Only five recessive mutations causing EI have been described, all of which are located in the central region of the KRT10 gene. In the current study, we aimed to identify the genetic defect underlying EI in a 12‐year‐old patient. Direct sequencing of the patient's genomic DNA revealed a novel homozygous nonsense mutation residing within the proximal part KRT10 first exon. The mutation was found to co‐segregate with the disease phenotype in an autosomal recessive fashion. Using real‐time quantitative PCR, we found an almost two‐fold decrease in KRT10 expression in the patient's skin compared with the skin of healthy controls. Western blot analysis showed complete absence of keratin 10 protein in the patient's skin, suggesting early protein degradation.     

Protein C global assay in the evaluation of women with idiopathic pregnancy loss

A number of strongly linked polymorphisms within the Factor V gene (FV HR2 haplotype) has been identified as a cause of resistance to activated protein C, and has suggested a modest risk factor for vein thrombosis. We investigated the frequency of the HR2 haplotype in 433 consecutive patients with confirmed deep vein thrombosis and 326 controls. The HR2 haplotype was more frequent in patients (15.2%) than in controls (10.1%). The risk of thrombosis among carriers of this haplotype was significantly increased (odds ratio: 1.6 [95% CI: 1.0-2.5]). The estimated risk associated with the HR2 haplotype was 1.8 (95% CI: 1.1-2.9) in subjects with (n = 255), and 1.4 (95% CI: 0.8-2.4) in those without (n = 178) acquired risk factors for vein thrombosis. After adjustment for sex, FV Leiden and FII A20210 mutations, the estimated risk of vein thrombosis among carriers of the HR2 haplotype was 1.8 (95% CI: 1.1-2.8). Present data indicate that the HR2 haplotype is independently associated with vein thrombosis among individuals with a high-risk profile.     

Liposome interactions with hydroxyapatite crystals: A possible mechanism in the calcification of atherosclerotic plaques

Summary Some stages in the calcification of atherosclerotic plaques may involve associations between lipids and hydroxyapatite (HA) by surface interactions. Liposomes, artifical membranous lipid vesicles, have been used in this study as model structures for biological calcification processes. Liposome (containing cholesterol and phosphatidylcholine in most cases) suspensions were prepared by sonication, after which HA seed crystals were added to the suspensions and stirred at 37°C. Aliquots of the liposome suspensions were analyzed for particle size distribution and by transmission electron microscopy and electron diffraction. The results showed that HA induced aggregation of liposomes and modifications of the microscopic shapes of the liposomes in the aggregates. These data can be explained by the electron diffraction pattern where superimposition of liposome reflection and crystal reflection exists and may suggest organic-inorganic interaction. The potential of HA crystals to induce formation of liposome aggregates may be seen as a step in atherosclerotic plaques calcification.