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Biomedical subjects

G R Sutherland

Publications and source records attributed to G R Sutherland.

At least 235 records · Page 13Linked to original sources
PubMed1995

A review of endocarditis in acquired immunodeficiency syndrome and human immunodeficiency virus infection.

Non-bacterial thrombotic endocarditis (NBTE) was frequently identified in early post-mortem studies of patients with HIV infection, but has not been reported since 1989. The reason for this apparent decline is not clear, but it is possible that the prevalence of the condition was overestimated in the past. We have found no evidence of NBTE in our series of 110 autopsies on subjects from all major risk groups and at various stages of immune deficiency [intravenous drug user (IVDU)-AIDS 35% (39/110), IVDU-pre AIDS 36% (40/110), homosexual-AIDS 25% (28/110), blood product recipients-AIDS 1.8% 2/110), African 0.9% (1/110)]. Infective endocarditis (IE) in HIV infection occurs almost exclusively in intravenous drug users and is rare in other HIV-positive patients. However, asymptomatic HIV infection appears to have little effect on the susceptibility to or the mortality from endocarditis and it is, therefore, appropriate to institute antimicrobial treatment in these cases. The majority (54.4%) of the 960 HIV-positive individuals in the Lothian region of Scotland are young adults who contracted the virus through IVDU around 1983. However, a prospective echocardiological study of 269 patients over four years (IVDU 69%, homosexual 18%, heterosexual 8%, bisexual 3%, multiple risk factors 1%) has demonstrated only four cases of infective endocarditis. We believe this reflects the prevalence of current parenteral drug use in our cohort which has fallen with the introduction of an oral drug replacement programme.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections↗
PubMed1995

Molecular basis of p(CCG)n repeat instability at the FRA16A fragile site locus.

Rare, folate-sensitive fragile sites are the result of the unstable expansion of trinucleotide p(CCG)n repeats, which are normally polymorphic in copy number. Differences in the number and frequency of alleles of the fragile site FRA16A p(CCG)n repeat were observed between different ethnic populations suggesting that certain alleles might be predisposed to instability. Sequence analysis demonstrated that the longer and more variable alleles were associated with loss of repeat interruption. Perfect repeat configuration therefore appears to be a necessary precondition for the instability associated with fragile site genesis.

Alleles↗
PubMed1995

Transoesophageal echocardiography in congenital heart disease.

The development of paediatric transoesophageal ultrasound imaging represents an important advance in the diagnosis and management of the patient with congenital heart disease. Although primary diagnostic transoesophageal studies are seldom indicated in infants and unoperated children, they have an important role in the older child, especially where there has been prior cardiac surgery. Diagnostic studies are most appropriate for abnormalities of venous return, the atria, atrioventricular valves and the left ventricular outflow tract. Two other important areas in which transoesophageal imaging is playing an increasing role in the management of the paediatric patient is in monitoring of surgical repair.

Cardiac Catheterization↗
PubMed1995

Colour Doppler myocardial imaging: potential applications in acquired and congenital heart disease.

Doppler myocardial imaging (DMI) is a new ultrasound technique which has been developed to allow colour Doppler imaging of cardiac structures as opposed to blood pool imaging. This is achieved by changing the velocity, filtering and threshold parameters of the standard colour Doppler algorithms. DMI parameters which can be measured are regional tissue velocity, acceleration and reflected Doppler energy. In addition, concomitant changes in the pulsed Doppler algorithms allow interrogation of instantaneous peak velocities during the cardiac cycle in the myocardial region in which the sample volume is placed. In both adult acquired heart disease and congenital heart disease, these new ultrasound parameters may provide new information on myocardial contractile function, diastolic function, myocardial perfusion and myocardial structure. The relative lack of image quality by chest wall attenuation inherent in the Doppler technique means that the methodology is potentially superior to standard grey-scale two-dimensional imaging in boundary detection and may prove to be of value in providing a robust boundary detection algorithm for use in volume calculations and in three-dimensional reconstruction of ventricular function.

Arrhythmias, Cardiac↗
PubMed1995

Bovine latent transforming growth factor beta 1-binding protein 2: molecular cloning, identification of tissue isoforms, and immunolocalization to elastin-associated microfibrils.

Monoclonal antibodies to fibrillin 1 (MP340), a component of elastin-associated microfibrils, were used to screen cDNA libraries made from bovine nuchal ligament mRNA. One of the selected clones (cL9; 1.2 kb) hybridized on Northern (RNA) blotting with nuchal ligament mRNA to two abundant mRNAs of 9.0 and 7.5 kb, which were clearly distinct from fibrillin mRNA (10 kb). Further library screening and later reverse transcription PCR by the rapid amplification of cDNA ends (RACE) technique resulted in the isolation of additional overlapping cDNAs corresponding to about 6.7 kb of the mRNA. The encoded protein exhibited sequence similarity of around 80% with a recently identified human protein named latent transforming growth factor beta 1 (TGF-beta 1)-binding protein 2 (LTBP-2), indicating that the new protein was bovine LTBP-2. This was confirmed by the specific localization of bovine LTBP-2 cDNA probes to human chromosome 14q24.3, which is the locus of the human LTBP-2 gene. The domain structure of bovine LTBP-2 is very similar to that of the human LTBP-2, containing 20 examples of 6-cysteine epidermal growth factor-like repeats, 16 of which have the consensus sequence for calcium binding, together with 4 examples of 8-cysteine motifs characteristic of fibrillins and LTBP-1. A 4-cysteine sequence which is unique to bovine LTBP-2 and which has similarity to the 8-cysteine motifs was also present. Antibodies raised to two unique bovine LTBP-2 peptides specifically localized in tissue sections to the elastin-associated microfibrils, indicating that LTBP-2 is closely associated with these structures. Immunoblotting experiments identified putative LTBP-2 isoforms as a 260-kDa species released into the medium by cultured elastic tissue cells and as larger 290- and 310-kDa species in tissue extracts. A major proportion of tissue-derived LTBP-2 required treatment with 6 M guanidine for solubilization, indicating that the protein was strongly bound to the microfibrils. Most of the guanidine-solubilized LTBP-2 appeared to be monomeric, indicating that it was not involved in disulfide-bonded aggregation either with itself or with latent TGF-beta. Additional LTBP-2 was resistant to solubilization with 6 M guanidine but was readily extracted with a reductive saline solution. This treatment is relatively specific for solubilization of microfibrillar constituents including fibrillin 1 and microfibril-associated glycoprotein. Therefore, it can be inferred that some LTBP-2 is bound covalently to the microfibrils by reducible disulfide linkages. The evidence suggests that LTBP-2 has a direct role in elastic fiber structure and assembly which may be independent of its growth factor-binding properties. Thus, LTBP-2 appears to share functional characteristics with both LTBP-1 and fibrillins.

Adaptor Proteins, Signal Transducing↗
PubMed1995

Cardiac involvement in Wegener's granulomatosis.

Wegener's granulomatosis is a systemic inflammatory disorder of unknown aetiology. The protean clinical presentations depend on the organ(s) involved and the degree of progression from a local to a systemic arteritis. The development of serological tests (antieutrophil cytoplasmic antibodies) allows easier diagnosis of a disease whose incidence is increasing. This is particularly helpful where the presentation is not classic--for example "overlap syndromes"--or where the disease presents early in a more localised form. This is true of cardiac involvement, which is traditionally believed to be rare, but may not be as uncommon as has hitherto been thought (< or = 44%). This involvement may be subclinical or the principal source of symptoms either in the form of localised disease or as part of a systemic illness. Pericarditis, arteritis, myocarditis, valvulitis, and arrhythmias are all recognised. Wegener's granulomatosis should therefore be considered in the differential diagnosis of any non-specific illness with cardiac involvement. This includes culture negative endocarditis, because Wegener's granulomatosis can produce systemic upset with mass lesions and vasculitis. Echocardiography and particularly transoesophageal echocardiography can easily identify and delineate cardiac and proximal aortic involvement and may also be used to assess response to treatment.

Adult↗
PubMed1995

Skeletal muscle contraction in healthy volunteers: assessment with Doppler tissue imaging.

PURPOSE: To evaluate Doppler tissue imaging (DTI) in the measurement and characterization of skeletal muscle movement and contraction. MATERIALS AND METHODS: Five healthy male subjects were examined with a commercially available ultrasound imaging unit modified for DTI. Velocities of the rectus femoris and gastrocnemius-soleus muscle motion were measured during the patellar and ankle reflexes, respectively. Velocity profiles were analyzed after digitization of the DTI images. Time to peak velocity, velocity range, and relaxation time were examined in each case over three contractions. For reflex contractions, reproducibility was examined by determining the latency period, area under the velocity curve, and duration of contraction for each of five consecutive reflexes. RESULTS: Isotonic muscle contraction could be distinguished from passive movement by a higher tissue velocity range, by a more rapid initial acceleration slope, and by the velocity differential across the muscle. The intensity and duration of the contraction and plateau and relaxation phases of isotonic contraction could be measured in all muscle groups. CONCLUSION: DTI provides detailed information about the dynamics of skeletal muscle contraction.

Adult↗
PubMed1995

The human OTF1 locus which overlaps the CD3Z gene is located at 1q22-->q23.

The human OTF1 locus encoding the Oct-1 protein has previously been mapped to chromosome 1 cen-->q32 by analysis of somatic cell hybrids. We report here the regional localization of OTF1 to 1q22-->q23 by fluorescence in situ hybridization. The physical linkage of the CD3Z gene to the OTF1 transcription unit also refines the location of the CD3Z locus to 1q22-->q23.

Chromosome Mapping↗
PubMed1995

Overlapping submicroscopic deletions in Xq28 in two unrelated boys with developmental disorders: identification of a gene near FRAXE.

Two unrelated boys are described with delay in development and submicroscopic deletions in Xq28, near FRAXE. Molecular diagnosis to exclude the fragile X (FRAXA) syndrome used the direct probe pfxa3, together with a control probe pS8 (DXS296), against PstI restriction digests of DNA. Deletions were detected initially by the control probe pS8, which is an anonymous fragment subcloned from YAC 539, within 1 Mb distal to FRAXA. Further molecular analyses determined that the maximum size of the deletion is < 100 kb in one boy (MK) and is wholly overlapped by the deletion of up to approximately 200 kb in the other (CB). These deletions lie between the sequences detected by the probe VK21C (DXS296) and a dinucleotide repeat VK18AC (DXS295). The patient MK had only speech delay with otherwise normal development, while patient CB had global developmental delay that included speech delay. Detection of overlapping deletions in these two cases led to speculation that coding sequences of a gene(s) important in language development may be affected. Hybridization of the pS8 and VK21A probes to zooblots revealed cross-species homology. This conservation during evolution suggested that this region contains sequences with functional significance in normal development. The VK21A probe detected a 9.5-kb transcript in placenta and brain and a smaller, 2.5-kb, transcript in other tissues analyzed.

Child, Preschool↗
PubMed1995

[Doppler tissue imaging: current status and future prospects].

Colour Doppler myocardial imaging is a new technique which allows the visualization in the colour Doppler of myocardial tissues, instead of blood pool imaging. To permit the acquisition of this information some modifications are essential in the machine. The gain has to be reduced so that, firstly, the echoes from ventricular walls were similar to those from the blood pool. Secondly the Doppler velocity range has to be reduced to correspond to the normal velocity of the ventricular wall. These modifications allow the tissue echoes to pass the clutter filter and to be displayed in colour on the video screen. This technique may be able to evaluate the velocity of myocardial tissue, the acceleration and the strength within the myocardial wall with these maps, obtained by modifications in the software, called Velocity Map, Acceleration Map, Energy Map. The clinical applications of this technique are: 1) in the area of myocardial functions e.g.: measurements, volumes, diastolic functions; 2) in the area of myocardial ischemia e.g.: wall motion abnormalities, viability studies, perfusion with contrast agents, stress echo, infarct identification; 3) in the area of myocardial depolarisation e.g.: arrhythmias evaluation, ablation monitoring. Doppler tissue imaging in spite of good results obtained, needs a large clinical studies.

Coronary Disease↗
PubMed1994

Isolation and chromosomal localization of a novel human G-protein-coupled receptor (GPR3) expressed predominantly in the central nervous system.

Degenerate oligonucleotide primers designed against known G-protein-coupled receptors were used in polymerase chain reaction amplification to isolate a novel receptor sequence (R4) from a rat insulinoma cell line and its human homolog (GPR3) from a human neuroblastoma cDNA library. The novel human receptor sequence is expressed in low abundance predominantly in the central nervous system and at low levels in the lung and kidney. The gene encoding GPR3 is intronless within the coding region, contains at least one intron in the 5'-untranslated region, and has been localized to chromosome 1p34.3. The activating ligand for the homologous receptors R4 and GPR3 is not known, but sequence similarity with the closely related orphan rat receptor R334 [FEBS Lett. 292:243 (1991)] suggests that R334 and the homologous receptors R4 and GPR3 probably represent two discrete molecular subtypes that interact with the same or closely related ligands.

Amino Acid Sequence↗
PubMed1994

The CD39 lymphoid cell activation antigen. Molecular cloning and structural characterization.

CD39, a 70- to 100-kDa molecule expressed primarily on activated lymphoid cells, was previously shown to mediate B cell homotypic adhesion when ligated with a subset of anti-CD39 mAbs. In the present study, we describe the cloning and molecular characterization of human and murine CD39. The nucleotide sequence of human CD39 includes an open reading frame encoding a putative 510 amino acid protein with six potential N-linked glycosylation sites, 11 Cys residues, and two potential transmembrane regions. Murine CD39 shares 75% amino acid sequence identity with human CD39 but fails to cross-react with anti-human CD39 mAbs. Although there were no significant similarities with other mammalian genes, considerable homology was found between CD39 and a guanosine diphosphatase from yeast. A series of mouse-human hybrid molecules was constructed to determine the general topology of CD39 and the location of a biologically functional epitope. These findings and supporting evidence from an anti-CD39 mAb-selected phage peptide display library indicate a likely model wherein a short intracellular N-terminus is followed by a large extracellular loop containing the epitope recognized by stimulatory anti-CD39 mAbs, and a short intracellular C terminus. The results demonstrate that CD39 is a novel cell surface glycoprotein with unusual structural characteristics.

Adenosine Triphosphatases↗
PubMed1994

Molecular characterization of murine and human OX40/OX40 ligand systems: identification of a human OX40 ligand as the HTLV-1-regulated protein gp34.

A ligand was cloned for murine OX40, a member of the TNF receptor family, using a T cell lymphoma cDNA library. The ligand (muOX40L) is a type II membrane protein with significant identity to human gp34 (gp34), a protein whose expression on HTLV-1-infected human leukemic T cells is regulated by the tax gene. The predicted structures of muOX40L and gp34 are similar to, but more compact than, those of other ligands of the TNF family. Mapping of the muOX40L gene revealed tight linkage to gld, the FasL gene, on chromosome 1. gp34 maps to a homologous region in the human genome, 1q25. cDNAs for human OX40 receptor were cloned by cross-hybridization with muOX40, and gp34 was found to bind the expressed human receptor. Lymphoid expression of muOX40L was detected on activated T cells, with higher levels found on CD4+ rather than CD8+ cells. The cell-bound recombinant ligands are biologically active, co-stimulating T cell proliferation and cytokine production. Strong induction of IL-4 secretion by muOX40L suggests that this ligand may play a role in regulating immune responses. In addition, the HTLV-1 regulation of gp34 suggests a possible connection between virally induced pathogenesis and the OX40 system.

Amino Acid Sequence↗
PubMed1994

Cloning, chromosomal mapping and characterization of the human metal-regulatory transcription factor MTF-1.

Metallothioneins (MTs) are small cysteine-rich proteins that bind heavy metal ions such as zinc, cadmium and copper with high affinity, and have been functionally implicated in heavy metal detoxification and radical scavenging. Transcription of metallothioneins genes is induced by exposure of cells to heavy metals. This induction is mediated by metal-responsive promoter elements (MREs). We have previously cloned the cDNA of an MRE-binding transcription factor (MTF-1) from the mouse. Here we present the human cDNA equivalent of this metal-regulatory factor. Human MTF-1 is a protein of 753 amino acids with 93% amino acid sequence identity to mouse MTF-1 and has an extension of 78 amino acids at the C-terminus without counterpart in the mouse. The factors of both species have the same overall structure including six zinc fingers in the DNA binding domain. We have physically mapped the human MTF-1 gene to human chromosome 1 where it localizes to the short arm in the region 1p32-34, most likely 1p33. Both human and mouse MTF-1 when produced in transfected mammalian cells strongly bind to a consensus MRE of metallothionein promoters. However, human MTF-1 is more effective than the mouse MTF-1 clone in mediating zinc-induced transcription.

Amino Acid Sequence↗