Lurching, reeling, waddling and staggering in mice--is carbonic anhydrase (CA) VIII a candidate gene?
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to C Kelly.
Explore the source record for details and available documents.
We performed high resolution computed tomography (HRCT) on the lungs of 20 patients with RA and clinical and radiological evidence of interstitial lung disease (ILD). A case control group of patients with RA but without evidence of ILD were similarly studied and all patients underwent detailed pulmonary function testing. Clinical findings, drug therapy, smoking status, the presence/absence of SS and disease activity were also assessed. HRCT showed a range of abnormalities among patients thought to have ILD. Interstitial fibrosis was confirmed in 16 but was frequently associated with emphysema. Ground glass opacification was present in seven, while basal honey-combing was also evident in seven patients. Both these features were present in two patients with ILD. Bronchiectasis was identified in six patients and was the predominant finding in two patients previously thought to have ILD. Among the control patients, HRCT was normal in only five. Clinically unsuspected ILD was present in four patients, while a further four had bronchiectasis. Pleural disease was identified in seven controls. Pulmonary function tests were generally poor predictors of HRCT findings, although a reduced residual volume (RV) [> 1 S.D.] was 83% specific for the presence of ILD and a raised RV [> 1 S.D.] was 64% specific for emphysema. Smoking did not correlate with the presence of either ILD or emphysema and there were no correlations between disease activity and HRCT findings. RA patients with evidence of ILD have abnormalities on HRCT which cannot be confidently predicted on any other non-invasive test.(ABSTRACT TRUNCATED AT 250 WORDS)
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The high affinity Fc gamma receptor, Fc gamma RI, is unique among the three classes of macrophage Fc gamma receptors not only in its affinity for IgG, but also in the structure of its cytoplasmic domain. Fc gamma RIIA and the gamma subunit of Fc gamma RIIIA have tyrosine-containing motifs within their cytoplasmic domains that are phosphorylated when crosslinked and that are required for phagocytosis by COS-1 cell transfectants. In contrast to these other Fc gamma receptors, Fc gamma RI does not contain cytoplasmic tyrosines and does not induce phagocytosis in COS-1 transfectants. We transfected wild-type (WT) and mutant (MT) Fc gamma RI lacking the cytoplasmic domain into COS-1 cells and murine macrophages and assessed phagocytosis using IgG-coated red blood cells (RBCs) and RBCs conjugated with Fab anti-human Fc gamma RI monoclonal antibody (mAb). Fc gamma RI, in contrast to Fc gamma RIIA, did not induce phagocytosis in COS cells. However, both WT and MT Fc gamma RI induced phagocytosis in murine macrophages, and phagocytosis was inhibited by the tyrosine kinase inhibitor tyrphostin 23. Human monocytes also phagocytosed Fc gamma RI-targeted RBCs, and activation of Fc gamma RI on monocytes with Fab anti-Fc gamma RI induced phosphorylation of Fc gamma RII on tyrosine residues. However, Fc gamma RI activation of Fc gamma RI-Fc gamma RIIA COS-1 cotransfectants did not induce tyrosine phosphorylation of Fc gamma RIIA, and coexpression of Fc gamma RI and Fc gamma RIIA in COS cells did not confer Fc gamma RI phagocytic capability. In contrast, coexpression in COS-1 cells of Fc gamma RI with the gamma subunit of Fc gamma RIIIA conferred phagocytic function to both Fc gamma RI and the MT Fc gamma RI lacking the cytoplasmic domain. Thus, Fc gamma RI does not require its cytoplasmic domain to mediate a phagocytic signal and interacts with the gamma subunit of Fc gamma RIIIA to induce phagocytosis.
The Markov model of molecular evolution has recently received a significant amount of interest because its statistical nature allows for the testing of a number of evolutionary hypotheses. Here we propose a test which assesses whether data from two species sharing a common ancestor will fit a general Markovian model. We illustrate the test with two examples of data which appear at first glance not to fit a Markov model.
Deliberate self-poisoning presenting at Craigavon Area Hospital in 1991 was examined and compared to the years 1976 and 1986. Self-poisoning has not declined over the 15 year period 1976-1991. The reduction in the use of benzodiazepines, and increase in paracetamol, previously reported, continues. Possible reasons for this are examined, in relation to local and national drug prescribing.
We have identified the third member of a family of cationic amino acid transporters in lipopolysaccharide-stimulated murine macrophages. The deduced amino acid sequence of this transporter is the same as MCAT-2 (mouse cationic amino acid transporter-2), the low affinity transporter expressed in hepatocytes, except for a stretch of 41 amino acids that connects the eighth and ninth membrane-spanning domains. These transporters apparently result from differential splicing of transcripts from a single gene and therefore have been named MCAT-2A (hepatocyte) and MCAT-2B (macrophage). Despite their similarity, MCAT-2B is saturated at one-fifth the arginine concentration, has a lower apparent Vmax, and is more sensitive to trans-stimulation than MCAT-2. Introduction of the unique regions of MCAT-2A and MCAT-2B into the equivalent portion of the related protein, MCAT-1, created chimeric transporters with properties most like the donor of this region. Our findings suggest these 41 amino acids contain a domain that binds the amino acid substrate during its translocation across the membrane.
Carbonic anhydrase is an essential metabolic enzyme of the central nervous system and has an important role in the production and regulation of cerebrospinal fluid. Although it has been known for over 30 years that inhibition of the enzyme with acetazolamide dramatically but not completely reduces the production of cerebrospinal fluid, the precise mechanism of the inhibitory action has been only recently revealed. In this study we present evidence that apart from carbonic anhydrase II, the catalytically highly active isozyme, carbonic anhydrase III, an acetazolamide-resistant and kinetically different isozyme could be demonstrated in the epithelial cells of the developing and mature rodent and human choroid plexuses. Both isozymes express intense immunostaining revealed with specific antisera, and by using in situ hybridisation histochemistry, carbonic anhydrase III mRNA was also observed. Since the kinetic properties and proportion of brain carbonic anhydrase III in the human choroid plexus are not revealed the function of this isozyme in choroid plexus is still to be determined.
OBJECTIVE: To define the role of HLA-DR phenotype in the expression of primary Sjögren's syndrome (SS). METHODS: A family study of Caucasian probands with definite primary SS was conducted. Relatives with features of primary SS were classified according to the Fox criteria. Several types of linkage analysis between primary SS and HLA haplotype (HLA-A, B, and DR) were performed. RESULTS: A trend toward haplotype sharing between affected siblings was evident for definite/probable primary SS when analyzed by the Green and Woodrow method. This reached statistical significance when data from other published family studies were included. LOD scores and analyses using the Penrose method showed little evidence of linkage. CONCLUSION: In view of the strong association with HLA-DR3, these results suggest that the HLA-DR3 allele is an important susceptibility factor for expression of primary SS in Caucasians. The apparent haplotype sharing may be a consequence of this association. The potential influence of other genetic factors (major histocompatibility complex [MHC] and non-MHC) is discussed.
We investigated a new means of diagnosing occult scaphoid fractures. Eighty-six patients underwent vibratory testing at presentation, while the clinical examination and standard four-view x-ray examination findings were unknown to the persons who performed the vibratory testing of both the injured and uninjured wrists. Thirty-six patients had radiographically confirmed scaphoid fractures and, after their vibratory tests, were eliminated from the study. Fifty patients, 39 men and 11 women, were believed to have scaphoid fractures on the basis of history and clinical examination findings but were included in the occult scaphoid study group because standard four-view x-ray films of the wrists did not reveal a scaphoid fracture. Distinction between the fracture and no-fracture patients was made with a limited two-phase technetium bone scan and delayed x-ray examination. All patients with known scaphoid fractures (36) had positive findings on vibratory examination. Vibratory testing identified all six of the patients with occult scaphoid fractures (sensitivity 100%). Results of two examinations were false-positive, and none were false-negative (specificity 95%). One of the patients with false-positive results had a fracture of the trapezium, and the other had reflex sympathetic dystrophy. The vibratory testing of injured wrists is inexpensive, noninvasive, and easy to perform, and it involves no ionizing radiation.
Actinomycetes form an enormous reservoir of secondary metabolites and enzymes. The potential for exploiting rare actinomycetes is highlighted by the discovery of novel compounds from strains of Spirillospora and Nocardioides. Novel compounds of well known classes of antibiotics, such as polyenes, continue to be discovered. For compounds containing a chromophore, the analysis by high-performance liquid chromatography coupled with a diode-array detector enables the elimination of producers of known compounds and facilitates the discovery of novel compounds or derivatives. The complexity of the regulatory mechanisms is illustrated by glutamine synthetase. The characterization of thermostable amylolytic, lignolytic, peroxidase and neuramidase activities, and the isolation of novel cellulolytic actinomycetes clearly demonstrate the potential of Actinomycetes as producers of enzymes.
One of the diagnostic criteria for cat-scratch disease is a positive delayed-type hypersensitivity skin test reaction to an antigen prepared from purulent material aspirated from a cat-scratch disease-involved lymph node. Polymerase chain reaction coupled with DNA sequence analysis was used to identify organisms found in these skin test antigen preparations that may be responsible for eliciting this response. Two independent sources of cat-scratch disease skin test antigens yielded DNA sequences characteristic of the newly described rickettsia, Rochalimaea henselae. These results coupled with previous serologic data strongly suggest that R. henselae plays a central role in the etiology of cat-scratch disease.
Autoimmune diseases and autoantibodies have been documented in 42 index cases with definite primary Sjögren's syndrome (1 degree SS), 207 relatives and 39 spouses. The results were compared with control data from a local population survey. Thyroid disease, 1 degree SS and their associated autoantibodies were the commonest autoimmune abnormalities observed and found predominantly in older female relatives. The HLA-DR3 phenotype associated with 1 degree SS, antinuclear factor, hypothyroidism, and thyroid microsomal antibody. Rheumatoid arthritis and systemic lupus erythematosus were not found in excess in the families. Primary Sjögren's syndrome is frequently associated with thyroid disease and we suggest that there is a common genetic predisposition between these diseases which differs from 2 degrees SS associated with rheumatoid arthritis and systemic lupus erythematosus. This includes MHC and non-MHC genes.
Lofepramine has been acclaimed as an effective and safe antidepressant, particularly for the elderly. Recent case reports of hepatic toxicity following treatment with lofepramine, however, caused clinicians to question its use in a patient population who frequently have concomitant physical illness. From published data the incidence of serious side effects as well as the implications for its use remain unclear. In this study, 52 patients over the age of 65 years treated with lofepramine were monitored over a 12-week period. The results suggest that for the overwhelming majority of patients, any rise in liver enzyme activity is transient. It is recommended, however, that LFTs be monitored for the first 12 weeks of treatment.