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Biomedical subjects

C Moss

Publications and source records attributed to C Moss.

At least 37 records · Page 2Linked to original sources
PubMed2000

Genetic skin disorders.

Neonatologists do not require a detailed knowledge of all genetic skin disorders but need to recognize one if they see it. The unique accessibility of the skin makes it possible to observe the physical signs and deduce the child's immediate needs from first principles. The morphological classification given here will help the nondermatologist establish a clinical diagnosis. Tremendous advances over the last 10 years in understanding the molecular basis of skin disease make it possible, in many cases, to confirm the diagnosis and to counsel the family accurately.

Albinism, Oculocutaneous↗
PubMed2000

A keratin 14 'knockout' mutation in recessive epidermolysis bullosa simplex resulting in less severe disease.

Epidermolysis bullosa simplex (EBS) is a blistering skin disease caused in most cases by mis-sense mutations in genes encoding the basal epidermal keratin (K) 5 and K14. The inheritance is usually autosomal dominant and the mutant keratin proteins appear to exert a dominant negative effect on the keratin intermediate filament cytoskeleton in basal keratinocytes. We report a child with a homozygous K14 mutation resulting in the complete absence of K14 protein in the epidermis; remarkably, he only had mild to moderate disease. Electron microscopy of a skin biopsy showed a marked reduction in numbers of keratin intermediate filaments in the basal keratinocytes. Immunofluorescence microscopy using monoclonal antibody LL001 against K14 showed no staining, suggesting a functional knockout of K14. Sequence analysis of genomic DNA revealed a homozygous mutation in codon 31 of K14 that resulted in a premature stop codon further downstream in exon 1. The child's mother, who is unaffected by the disease, is heterozygous for the mutation. The consanguineous father was unaffected and unavailable for testing. The resulting mRNA is predicted to encode a protein of 116 amino acids, of which the first 30 are identical to the normal K14 sequence, and the remaining 86 residues are mis-sense sequence. Four previously reported cases of autosomal recessive EBS with functional knockout of K14 were severely affected by blistering, in contrast to our patient in whom the predicted protein has only the first 30 amino acids of K14 and is therefore the closest to a true knockout of K14 protein yet identified.

Consanguinity↗
PubMed1999

Cytogenetic and molecular evidence for cutaneous mosaicism: the ectodermal origin of Blaschko lines.

The idea that skin disorders following Blaschko lines represent genetic mosaicism is widely accepted. It seems likely that the two skin types represent the two different genotypes, but this has been remarkably difficult to prove, most studies showing a mixture of cell types in biopsies from both types of skin. Only for linear epidermolytic hyperkeratosis has it been possible to show mutant cells confined to the abnormal streaks. The hypothesis proposed here to explain this paradox is that disorders following Blaschko lines are due to mutations in genes expressed in epidermal cells (keratinocytes and melanocytes) rather than in dermal fibroblasts. The work on epidermolytic hyperkeratosis used keratinocytes, whereas most studies have used skin fibroblasts. Almost all disorders following Blaschko lines are epidermal: inflammatory, dysplastic, dyskeratotic, appendage-related, or pigmentary, and the remainder can be explained on the basis of epidermal influences on the dermis. If this hypothesis is correct, it points to a useful model system for elucidating the genetic component of common dermatoses sometimes found in Blaschko lines namely eczema, psoriasis, lichen planus, and vitiligo.

Chimera↗
PubMed1999

Selection of topics and questions for the 2001 Census.

The Government's proposals for questions to be asked in the 2001 Census were published in a White Paper in March this year. The wide range of topics proposed for inclusion represent the culmination of extensive user consultation and testing. Questions have been shown to meet specified criteria in relation to user need, availability of alternative sources, quality, public acceptability and burden on respondents. Significant changes from the 1991 Census include: new questions on general health, provision of unpaid care, time since last paid employment and size of employer's organisation; and major revisions to questions on relationship within the household, ethnic group, and qualifications. A new question on religion is also proposed for England and Wales, however this is subject to a change in Census Legislation. A strong case has been made for the inclusion of a question on income, but the Government has yet to make firm proposals in this respect.

Censuses↗
PubMed1998

Preliminary observations on ascidian and echinoderm neurons and neural explants in vitro.

As part of a study on echinoderm and ascidian neural regeneration, attempts were made to develop a system for the maintenance of their neurons in vitro. It was found that neurons and neural tissue explants from the starfish, Asterias rubens, and the brittlestar, Ophiura ophiura, and explants from the brain of the ascidian, Ciona intestinalis, could be cultured for up to 6 weeks in a modified L15-based medium. Some cells extended axonal projections and produced growth cones under certain conditions. Attempts were made to stimulate neuron survival and outgrowth of echinoderm cultures with conditioned media containing growth factors or tissue extracts and with various substrates including extracellular matrix extracts from native tissue. Ascidian brain explants from both normal and regenerating animals were cultured in the standard conditions established for echinoderm tissue, with outgrowth being observed in 25% of explants. In these cultures labelling with bromodeoxyuridine suggested that regeneration continues in vitro, although results using substance P immunocytochemistry indicate neuronal differentiation may be impeded. These preliminary studies suggest it is possible to maintain adult echinoderm and ascidian neurons in vitro.

Animals↗
PubMed1997

Missense mutations in keratin 17 cause either pachyonychia congenita type 2 or a phenotype resembling steatocystoma multiplex.

Pachyonychia congenita (PC) is a group of autosomal dominant ectodermal dysplasias in which the main phenotypic characteristic is hypertrophic nail dystrophy. In the Jackson-Lawler form (PC-2), pachyonychia is accompanied by multiple pilosebaceous cysts, natal teeth, and hair abnormalities. By direct sequencing of genomic PCR products, we report heterozygous K17 missense mutations in the same conserved protein motif in a further five PC-2 families (K17 N92S in one familial and three sporadic cases; K17 Y98D in one familial case) confirming that mutations in this gene are a common cause of PC-2. We also show heterozygous missense mutations in K17 (N92H and R94H) in two families diagnosed as steatocystoma multiplex. Mild nail defects were observed in some but not all of these patients on clinical re-evaluation of these families. All the K17 mutations reported here were shown to co-segregate with the disease in the pedigrees analyzed and were excluded from 100 unaffected, unrelated chromosomes by restriction enzyme analysis of K17 genomic PCR products. We conclude that phenotypic variation is observed with K17 mutations, as is the case with other keratin disorders.

Cysts↗
PubMed1996

Percutaneous dilatational tracheostomy. A safe, cost-effective bedside procedure.

OBJECTIVE: To evaluate the safety and cost-effectiveness of percutaneous dilatational tracheostomy performed in the intensive care unit. DESIGN: Retrospective review of 65 patients with cost-effectiveness analysis. SETTING: University-affiliated tertiary care teaching hospital with a 34-bed combined medical-surgical intensive care unit. PATIENTS: All patients who underwent percutaneous dilatational tracheostomy under the supervision of a single general surgeon during a 19-month period. Cost analysis was based on comparison with standard operative tracheostomies performed during the same period. RESULTS: Percutaneous dilatational tracheostomy was completed in all patients in whom it was attempted, regardless of airway anatomy, body habitus, and ventilator settings. The mean duration of the procedure performed in the intensive care unit was 13.6 minutes (95% confidence interval, 11.7 to 15.5 minutes). Intraoperative complications occurred in 14 patients (22%), most of which were minor technical difficulties, and none resulted in serious morbidity. Postoperative complications occurred in six patients (9%), including one death secondary to premature decannulation, three bleeding complications, one episode of subcutaneous emphysema, and one air leak. Two long-term airway complications after percutaneous dilatational tracheostomy were documented during a mean 7.5-month follow-up of 28 patients. Mean patient charges for the procedure performed in the intensive care unit by a surgeon, nurse, and respiratory therapist were $997 (95% confidence interval, $975 to $1018) compared with $2642 (95% confidence interval, $2513 to $2772) for standard tracheostomy (P<.001). This represented a savings of $1645 (95% confidence interval, $1492 to $1798) per tracheostomy. CONCLUSIONS: Percutaneous dilatational tracheostomy is a safe, rapid, cost-effective alternative to standard open tracheostomy. It can be performed at the bedside, obviating the need to transport critically ill patients from their optimal intensive care unit environment.

Adolescent↗
PubMed1996

Osteogenic sarcoma in the Rothmund-Thomson syndrome.

Two children who had the Rothmund-Thomson syndrome and developed osteosarcoma are reported. The 10 previously reported cases are reviewed. The osteosarcomas developed at a younger age than normally expected and 66% occurred in the tibia/fibula. Four of the five patients for whom information was available showed undue sensitivity to cancer chemotherapy agents with prolonged myelosuppression and severe mucositis. It is recommended that doxorubicin in particular should be given with extreme caution in such patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

A recurrent homozygous nonsense mutation within the LAMA3 gene as a cause of Herlitz junctional epidermolysis bullosa in patients of Pakistani ancestry: evidence for a founder effect.

The anchoring filament protein laminin 5 is abnormally expressed in the skin of patients with Herlitz junctional epidermolysis bullosa (H-JEB). In this study, we performed mutational analysis on genomic DNA from a H-JEB child of first-cousin Pakistani parents, and identified a homozygous C-to-T transition in the LAMA3 gene of laminin 5 resulting in a premature termination codon (CGA-TGA) on both alleles. This mutation, R650X, has been previously reported in two other seemingly unrelated H-JEB individuals of Pakistani ancestry. Although this mutation may represent a mutational hotspot within the LAMA3 gene, haplotype analysis based on a silent intragenic polymorphism (GCC/GCG, alanine 429; GenBank no. L34155), and on three flanking microsatellite polymorphism (D18S45, D18S478, and D18S480), suggests that a common ancestral allele may be present in all three cases.

Base Sequence↗
PubMed1996

A recurrent mutation, ala391glu, in the transmembrane region of FGFR3 causes Crouzon syndrome and acanthosis nigricans.

Mutations in the fibroblast growth factor receptor 2 (FGFR2) gene have previously been identified in Crouzon syndrome, an autosomal dominant condition involving premature fusion of the cranial sutures. Several different missense and other mutations have been identified in Crouzon syndrome patients, clustering around the third immunoglobulin-like domain. We report here the identification of a mutation in the transmembrane region of FGFR3, common to three unrelated patients with classical Crouzon syndrome and acanthosis nigricans, a dermatological condition associated with thickening and abnormal pigmentation of the skin. The mutation within the FGFR3 transcript was determined by direct sequencing as a specific gcg to gag transversion, resulting in an amino acid substitution ala391glu within the transmembrane region.

Acanthosis Nigricans↗
PubMed1995

A homozygous nonsense mutation in the alpha 3 chain gene of laminin 5 (LAMA3) in Herlitz junctional epidermolysis bullosa: prenatal exclusion in a fetus at risk.

Mutations in the three genes (LAMA3, LAMB3, and LAMC2) that encode the three chains (alpha 3, beta 3, and gamma 2, respectively) of laminin 5, a protein involved in epidermal-dermal adhesion, have been established as the genetic basis for the inherited blistering skin disorder, Herlitz junctional epidermolysis bullosa (H-JEB). In this study, we performed mutational analysis on genomic DNA from a child with H-JEB and identified a nonsense mutation in the alpha 3 chain gene (LAMA3) consisting of a homozygous C-to-T transition resulting in a premature termination codon (CGA-->TGA) on both alleles. The parents were shown to be heterozygous carriers of the same mutation. Direct mutation analysis was used to perform DNA-based prenatal diagnosis from a chorionic villus biopsy at 10 weeks' gestation in a subsequent pregnancy. The fetus was predicted to be genotypically normal with respect to the LAMA3 mutation.

Base Sequence↗
PubMed1995

Human piebaldism: relationship between phenotype and site of kit gene mutation.

Human piebaldism is a rare autosomal dominant disorder characterized by congenital depigmented patches of skin and hair. Piebaldism results from mutations of the kit proto-oncogene, which encodes a cell-surface receptor, tyrosine kinase, whose ligand is the stem/mast cell growth factor. We report four unrelated patients with piebaldism and consider the variations in phenotype in relation to the site of the kit gene mutation.

Adolescent↗
PubMed1995

Island flaps including the Bezier type in the treatment of malignant melanoma.

Despite the trend in current surgical practice in the treatment on melanoma to produce smaller excisional defects, any technique which can introduce a surgical closure that does not require split skin grafting must be of benefit. This paper introduces and illustrates a range of island flap techniques that employ no skin grafting for the treatment of malignant melanoma defects. The new cutaneous island flap described, termed the Bezier or the French Curve, employs a double V-Y appositional closure method, thus giving a more refined reconstructive result that fits into the line of the body curves aesthetically. The design of the Bezier flap is almost identical in size and shape to the excisional defect, with a facial or muscular base for vascular support. Appropriate guidelines that determine the design and application of this island flap technique are listed. They are illustrated both diagrammatically and clinically. Other flaps illustrated include fasciocutaneous island flaps and myocutaneous island flaps that use a single V-Y flap appositional closure technique. All these flaps were designed with special reference to the dermatomes, which act as an aid memoire upon which the flaps are marked.

Adolescent↗