Search PubMed⌕ Search

Biomedical subjects

M Super

Publications and source records attributed to M Super.

At least 55 records · Page 3Linked to original sources
PubMed1995

Behavioural aspects and psychiatric findings in Noonan's syndrome.

This study describes the behavioural phenotype and psychiatric symptoms of 21 children with Noonan's syndrome attending a paediatric genetics clinic. Data from the behavioural phenotypes questionnaire are presented that suggest that children with Noonan's syndrome tend to be clumsy, stubborn, irritable, have communication difficulties, and are 'faddy eaters'. Nearly 50% of the patients with Noonan's syndrome were psychiatric 'cases' as assessed by a standardised measure.

Adolescent↗
PubMed1995

Infantile osteopetrosis; bone marrow transplantation from a cousin donor.

The successful correction of infantile osteopetrosis in an Asian child by bone marrow transplantation (BMT) from an HLA-A,B matched cousin donor is reported. Retrospective HLA molecular analysis revealed that patient and donor were incompatible for HLA-DPB1. Donor type cells detected in the patient after transplantation indicate successful engraftment. The patient is currently alive and well.

Bone Marrow Transplantation↗
PubMed1994

Active cascade testing for carriers of cystic fibrosis gene.

OBJECTIVE: To examine the acceptability, practicability, efficiency, and application of active screening for carriers of the cystic fibrosis gene in the extended families of those in whom the disease is present (Cascade screening). DESIGN: Paediatricians and physicians provide details of their affected patients, pedigrees are drawn up, and relatives offered tests after initial contact by the affected nuclear families. Affected patients are genotyped in a laboratory with a special interest in the genetics of cystic fibrosis. SETTING: North Western health region. SUBJECTS: Relatives and partners of 607 people with cystic fibrosis. INTERVENTIONS: Genetic counselling by letter for people found to be carriers; formal genetic counselling and when indicated arrangements for prenatal diagnosis for couples discovered to be carriers. MAIN OUTCOME MEASURES: Number of carrier couples detected; action in pregnancy of detected carrier couples; extent of the uptake of screening by relatives. RESULTS: Of 1563 relatives or partners tested, 15 carrier couples were detected; of nine pregnancies undertaken by these 15, eight had prenatal tests and three terminated pregnancies. An average of 16 people per family have come forward for testing so far. CONCLUSIONS: Cascade screening for carriers of cystic fibrosis is well accepted by relatives, especially on the mother's side of the family; it is 10 times more efficient in detecting carrier couples than unfocused screening. Detected carrier couples make practical use of the information in pregnancy. Active cascade screening for carriers is effective in cystic fibrosis and widespread application is recommended. These principles could be applied to other recessive disorders.

Cystic Fibrosis↗
PubMed1994

The exon-intron structure and chromosomal localization of the mouse macrophage mannose receptor gene Mrc1: identification of a Ricin-like domain at the N-terminus of the receptor.

The macrophage mannose receptor is a transmembrane protein that is expressed on the surface of mature macrophages. The ectodomain of the receptor contains multiple domains, eight of which belong to the calcium-dependent C-type lectin family. The mannose receptor binds to carbohydrate polymers that have a high content of mannose. This property allows this protein to function as a phagocytic receptor that participates in first-line host defense against invading microorganisms. In this paper we describe the intron-exon structure of the mouse macrophage mannose receptor gene which was found to span at least 70 kilobases. We also report the localization of this gene, termed Mrc1, to mouse Chromosome 2. Like its human counterpart, Mrc1 contains 30 exons and 29 introns. A protein module that resembles a subdomain of the B chain of the plant lectin Ricin has been found within the N-terminal cysteine-rich domain of the mannose receptor.

3T3 Cells↗
PubMed1994

Evaluation of two commercial jet nebulisers and three compressors for the nebulisation of antibiotics.

Nebulised antibiotics have been shown to be beneficial in the treatment of lung infections in cystic fibrosis. Studies on the efficiency of nebuliser systems are constantly required in view of the large number of compressor/drug/nebuliser combinations which are possible and the development of new systems and drugs. Six combinations of three commercially available compressors were compared (PortaNeb 50 (Medic-Aid; 5.4-6.1 l/min), Turboneb (Medix; 8.3-9.1 l/min), and CR 60 (Medic-Aid; 7.3-7.8 l/min)) and two jet nebulisers (Microneb III (Lifecare) and System 22 Acorn (Medic-Aid)) for the nebulisation of colomycin, gentamicin, and ciprofloxacin. Aerosol droplet size, nebulisation time, and aerosol output were determined. Turboneb and CR 60 reduced the nebulisation time and produced higher proportions of 'respirable' (< 5 microns diameter) antibiotic aerosols. The residual volume of the Microneb III was lower than that of the System 22 Acorn. It was found that the Turboneb and CR 60, when coupled with either Microneb III or System 22 Acorn, were suitable for the nebulisation of all three antibiotics. Of the equipment tested, Turboneb coupled with Microneb III was the most efficient combination. Even with this combination, only around 50% of the nominal dose was released as respirable aerosol.

Administration, Inhalation↗
PubMed1994

Amino acid substitutions of conserved residues in the carboxyl-terminal domain of the alpha 1(X) chain of type X collagen occur in two unrelated families with metaphyseal chondrodysplasia type Schmid.

Type X collagen is a homotrimeric, short-chain, nonfibrillar extracellular-matrix component that is specifically and transiently synthesized by hypertrophic chondrocytes at the sites of endochondral ossification. The precise function of type X collagen is not known, but its specific pattern of expression suggests that mutations within the encoding gene (COL10A1) that alter the structure or synthesis of the protein may cause heritable forms of chondrodysplasia. We used the PCR and the SSCP techniques to analyze the coding and upstream promoter regions of the COL10A1 gene in a number of individuals with forms of chondrodysplasia. Using this approach, we identified two individuals with metaphyseal chondrodysplasia type Schmid (MCDS) with SSCP changes in the region of the gene encoding the carboxyl-terminal domain. Sequence analysis demonstrated that the individuals were heterozygous for two unique single-base-pair transitions that led to the substitution of the highly conserved amino acid residue tyrosine at position 598 by aspartic acid in one person and of leucine at position 614 by proline in the other. The substitution at residue 598 segregated with the phenotype in a family of eight (five affected and three unaffected) related persons. The substitution at residue 614 occurred in a sporadically affected individual but not in her unaffected mother and brother. Additional members of this family were not available for further study. These results suggest that certain amino acid substitutions within the carboxyl-terminal domain of the chains of the type X collagen molecule cause MCDS. These amino acid substitutions are likely to alter either chain recognition or assembly of the type X collagen molecule, thereby depleting the amount of normal type X collagen deposited in the extracellular matrix, with consequent aberrations in bone growth and development.

Alleles↗
PubMed1993

Cranial hemihypertrophy with ipsilateral naevoid streaks, intellectual handicap and epilepsy: a report of two cases.

Two cases are described which presented with diffuse swelling of one cheek and hypertrophy of the underlying maxilla and mandible. Both children developed verrucous pigmented streaks over the area of swelling, and had epilepsy and severe mental subnormality. One of the children had a contralateral hemiplegia and his condition had a progressive course. The other child had no focal neurological signs and his disease seemed to be non-progressive. Although the facial appearance of both children suggested the diagnosis of encephalocrainiocutaneous lipomatosis syndrome, it was not possible to demonstrate the presence of any lipomata in either case. The literature relating to encephalocraniocutaneous lipomatosis is reviewed, as well as that relating to the syndromes of naevus unius lateris, the Proteus syndrome and the syndrome of cranial hemihypertrophy, and the clinical features of our two cases are compared with the features of these four syndromes.

Brain↗
PubMed1993

Human mannose-binding protein functions as an opsonin for influenza A viruses.

Influenza A viruses (IAVs) cause substantial morbidity and mortality in yearly epidemics, which result from the ability of the virus to alter the antigenicity of its envelope proteins. Despite the rapid replication of this virus and its ability to infect a wide variety of cell types, viremia is rare and the infection is generally limited to the upper respiratory tract. The preimmune host defense response against IAV is generally, therefore, successful. We have previously provided (and summarized) evidence that neutrophils contribute to defense against IAV, although neutrophil dysfunction and local tissue damage may be less salutory byproducts of this response. Here we provide evidence that the serum lectin mannose-binding protein directly inhibits hemagglutinin activity and infectivity of several strains of IAV. In addition mannose-binding protein acts as an opsonin, enhancing neutrophil reactivity against IAV. Opsonization of IAV by mannose-binding protein also protects the neutrophil from IAV-induced dysfunction. These effects are observed with physiologically relevant concentrations of mannose-binding protein. Two different allelic forms of recombinant mannose-binding protein are found to have similar effects. We believe, on the basis of these data, that mannose-binding protein alone and in conjunction with phagocytic cells is an important constituent of natural immunity (i.e., preimmune defense) against IAV.

Acute-Phase Proteins↗
PubMed1992

Characterization of the murine macrophage mannose receptor: demonstration that the downregulation of receptor expression mediated by interferon-gamma occurs at the level of transcription.

The macrophage mannose receptor (MMR) is a 175-Kd cell-surface transmembrane glycoprotein that is expressed on tissue macrophages where it functions both to mediate the uptake of mannose-rich glycoproteins and as a phagocytic receptor for bacteria, yeasts, and other pathogenic microorganisms. In this report we describe the cloning of the full-length cDNA of the mouse macrophage mannose receptor and we investigate the level at which interferon gamma (IFN-gamma) downregulates mannose receptor expression. The latter is a marker of the functional state of the cell as high levels are expressed on resident and inflammatory macrophages, whereas cells activated by treatment with IFN-gamma have decreased-to-absent cell-surface mannose receptor expression. The murine MMR cDNA contains an open reading frame that predicts a protein of 1,456 amino acids. Transient expression of the protein in heterologous cells shows that this cDNA encodes a functional mannose receptor. The deduced amino acid sequence of this protein has an overall 82% homology with the human mannose receptor and as such, the ectodomain contains an N-terminus that is cysteine-rich followed by a fibronectin type II domain and eight carbohydrate recognition domains (CRDs). The ectodomain is linked to a hydrophobic transmembrane region and a 46-amino acid cytoplasmic tail. All of the eight CRDs are particularly well conserved, especially CRD4, which shows 92% homology with the equivalent region of the human protein. Steady-state levels of murine MMR mRNA were measured in the macrophage cell line J774E, which is known to express the protein at the cell surface. These levels were decreased by a 4- to 8-hour incubation with IFN-gamma, but were almost abolished by overnight treatment with this cytokine. Nuclear run-on experiments showed that IFN-gamma inhibits MMR gene transcription. Therefore, the regulation of mannose receptor expression by IFN-gamma provides a novel system in which to study the mechanisms by which this cytokine represses gene expression.

Amino Acid Sequence↗
PubMed1992

Mutations of the cystic fibrosis gene locus within the population of the Northwest of England.

A large group of patients with cystic fibrosis (CF) from the Northwest of England were analysed for mutations within the CF gene. Eleven separate mutations were identified comprising 91.5% of the responsible genes. Molecular confirmation of a CF diagnosis becomes possible in 84% of cases. Only 1.19% of cases negative for the nine mutations have CF. The results of molecular analysis in this population have useful implications in respect of diagnosis validation and population carrier screening.

Adolescent↗