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Biomedical subjects

C Kelly

Publications and source records attributed to C Kelly.

At least 163 records · Page 9Linked to original sources
PubMed1991

Lung function in primary Sjögren's syndrome: a cross sectional and longitudinal study.

Clinical and radiological assessment of 100 patients (97 female) with primary Sjögren's syndrome was performed within six months of diagnosis in conjunction with spirometry and measurement of transfer factor for carbon monoxide (TLCO). This was repeated in an unselected subgroup of 30 patients after a mean interval of four years. On initial assessment, 43 patients had symptoms of lung disease and 10 had related physical signs; the chest radiograph was abnormal in five. There was a significant reduction (more than 2 standardised residuals) in forced expiratory volume in one second (FEV1), vital capacity (VC), and TLCO in 14, 12, and 10 patients, 24 patients overall having a significant reduction in one or more of these measures. There was a strong relation between reduction in lung function and both pulmonary symptoms and a lip biopsy specimen positive for Sjögren's syndrome. Lung function at the initial assessment in the 30 patients who were restudied was almost identical to that of the group as a whole. Seventeen now had symptoms and nine had related physical signs. The chest radiograph was abnormal in four patients. More patients had a significant reduction in FEV1, VC, and TLCO. Lung disease is sometimes an early feature of primary Sjögren's syndrome and may progress over a relatively short period.

Adolescent↗
PubMed1991

Human Fc gamma RII, in the absence of other Fc gamma receptors, mediates a phagocytic signal.

Fc gamma receptors are important components in the binding and phagocytosis of IgG-sensitized cells. Studies on the role of these receptors have been limited by the fact that most hematopoietic cells express more than one Fc gamma receptor. We studied the role of Fc gamma RIIA in isolation on a human erythroleukemia cell line (HEL) which expresses Fc gamma RIIA as its only Fc gamma receptor. HEL cells were observed to bind and phagocytose IgG-sensitized red blood cells (RBCs) in a dose-dependent manner. We then examined the role of Fc gamma RI and Fc gamma RII in isolation and in combination, in transfected COS-1 cells. Fc gamma RIIA-transfected COS cells also mediated both the binding and phagocytosis of IgG-sensitized RBCs. In contrast, phagocytosis was not observed in Fc gamma RI-transfected cells, although these cells avidly bound IgG-sensitized RBCs. Furthermore, coexpression of both receptors by doubly transfected cells did not affect the phagocytic efficiency of Fc gamma RIIA. These studies establish that Fc gamma RIIA can mediate phagocytosis and suggest that transfected COS-1 cells provide a model for examining this process. Since HEL cells exhibit characteristics of cells of the megakaryocyte-platelet lineage, including expression of Fc gamma RII as the only Fc gamma receptor, Fc gamma RIIA on megakaryocytes and platelets may be involved in the ingestion of IgG-containing immune complexes. Furthermore, these studies indicate that Fc gamma RI and Fc gamma RIIA differ in their requirements for transduction of a phagocytic signal.

Antigens, Differentiation↗
PubMed1990

Sequencing and characterization of the 185 kDa cell surface antigen of Streptococcus mutans.

The gene spa P (formerly designated as spa P1) encoding the Mr 185,000 surface antigen I/II of Streptococcus mutans, serotype c (strain NG5) has been sequenced. The deduced amino acid sequence of antigen I/II (1561 residues) includes a putative signal peptide (residues 1-38), as well as a transmembrane region (residues 1537-1556). The N-terminal part of the protein (residues 39-550) is particularly rich in alanine and includes three tandem repeats of a sequence of 82 residues. This region is predicted to be alpha-helical, adopting a coiled-coil formation, and may account for the cell surface hydrophobicity associated with expression of antigen I/II. In contrast the C-terminal region (residues 800-1549) is proline-rich, favouring an extended conformation. Comparison with the sequence determined from Strep. mutans strain MT8148 showed that antigen I/II is highly conserved with the exception of a short central region (residues 750-805). N-terminal sequencing of purified antigens I and II components indicated that antigen I extends from the amino-terminus of the intact Mr 185,000 surface antigen while antigen II extends from residue 996.

Amino Acid Sequence↗
PubMed1990

Expression of carbonic anhydrase in neisseriae and other heterotrophic bacteria.

A diverse range of heterotrophic bacteria was screened for the presence of carbonic anhydrase (CA) activity, sensitivity to inhibition of growth by acetazolamide (CA inhibitor), and the presence of protein binding monospecific antibody prepared against purified Neisseria sicca CA. CA activity was demonstrated only in strains of N. sicca and N. gonorrhoeae. However, all Neisseria strains, including various isolates of N. meningitidis and N. lactamica, were sensitive to acetazolamide, when grown in air, and showed serological cross-reaction with N. sicca CA. Strains of other genera were resistant to acetazolamide. A number of strains including members of the genera Pseudomonas, Staphylococcus, Streptococcus, Serratia and Proteus also strongly expressed a gene product(s) immunologically related to CA. The presence of CA cross-reacting proteins, which lack hydrase activity, is discussed in relation to the function of the various mammalian CA isoenzymes.

Acetazolamide↗
PubMed1990

An investigation into the mechanism of protection by local passive immunization with monoclonal antibodies against Streptococcus mutans.

Local oral passive immunization with Streptococcus mutans-specific monoclonal antibody (MAb) (Guy's 13) prevented recolonization by indigenous S. mutans in human volunteers who had first been treated with a conventional antibacterial agent (chlorhexidine). The F(ab')2 fragment of the MAb was as protective as the intact immunoglobulin G, but the Fab fragment of the molecule failed to prevent recolonization of S. mutans. In subjects receiving the MAb Fab fragment, S. mutans levels in dental plaque and saliva reappeared at a similar rate to that found in sham-immunized subjects who received either saline or a nonprotective MAb. In vitro, MAb had no bacteriostatic or bacteriocidal effect on S. mutans. However, S. mutans grown in the presence of either intact immunoglobulin G MAb or the F(ab')2 fragment formed very long chains, which resulted in clumping of the cells. S. mutans grown with either saline or the MAb Fab fragment formed significantly shorter chains, more characteristic of streptococcal growth in liquid media. The results suggest that the two binding sites of the MAb molecule may be an essential feature for preventing streptococcal colonization but that the ability to bind to phagocytes and activate complement which resides in the Fc fragment is not essential. Protection against colonization by S. mutans lasting up to 2 years was observed in immunized subjects, although MAb was applied over a period of only 3 weeks. Furthermore, functional MAb was detected up to 3 days following application of MAb to the teeth. The long-term protection could not be accounted for by a persistence of MAb on the tooth surface, and we have suggested that it may be due to a shift in the balance of the oral flora which discouraged recolonization by S. mutans. However, examination of the proportions of Streptococcus sanguis and veillonella species in the recolonization experiments failed to reveal a significant change in the proportions of either organism, which returned to approximately the preexperimental levels in both the immunized and control groups. These findings confirm the in vivo functional specificity of the MAb to S. mutans but are not consistent with the suggestion that S. sanguis or veillonella take over the niche vacated by S. mutans, unless the shift in the proportion of these organisms cannot be detected by the method used.

Adult↗
PubMed1990

DQw7 and the C4B null allele in rheumatoid arthritis and Felty's syndrome.

DQ beta and C4 null alleles have been defined in patients with rheumatoid arthritis, Felty's syndrome, and in control subjects. Comparison of DR4 positive subjects shows that rheumatoid disease without extra-articular features has no preferential associations with either DQ beta or C4 null variants. In Felty's syndrome there are significant associations with both the class II major histocompatibility complex (MHC) DQw7 allele (86% of DR4 positive patients with Felty's syndrome and 53% of DR4 positive controls) and the class III MHC C4B null allele (50% of patients with Felty's syndrome and 20% of DR4 positive controls). DQw7 and the C4B null allele are in linkage disequilibrium and the B44-Bf *S-C4A*3-C4B*Q0-DR4-DQw7 haplotype accounts for five of 24 DR4 positive haplotypes assigned in subjects with Felty's syndrome. The results were not accounted for by articular disease severity and suggest that articular and extra-articular forms of rheumatoid disease may be immunogenetically heterogeneous.

Alleles↗
PubMed1989

Sequence analysis of the cloned streptococcal cell surface antigen I/II.

The gene spa P (formerly designated as spa P1) encoding the Mr 185,000 surface antigen (I/II) of Streptococcus mutans, serotype c (NG5), has been sequenced. The gene (4683 bp) encodes a protein of 1561 amino acid residues including putative signal peptide (residues 1-38) and transmembrane (residues 1537-1556) sequences. The N-terminal region (60-550) has alanine-rich repeats and is predicted to be alpha-helical. However, the C-terminal region (800-1540) is proline-rich and favours an extended structure. Except for a short central variable region the sequences appear to be highly conserved for S. mutans serotype c. N-Terminal sequencing of separated antigen I and antigen II polypeptides suggests that the former represents the N-terminal and the latter the C-terminal portions of the intact antigen.

Amino Acid Sequence↗
PubMed1989

Effect of sodium thiosulfate on the pharmacokinetics and toxicity of cisplatin.

Concurrent administration of sodium thiosulfate (STS) can protect against the nephrotoxic effects of even very-high-dose cisplatin (CDDP) (i.e., 270 mg/m2 given intraperitoneally). The effect of STS on the pharmacology and toxicity of CDDP was investigated in patients receiving at each treatment 90 mg of CDDP/m2 intraperitoneally, with STS given concurrently on alternate cycles by the intravenous route. The patients received a total of 38 courses of therapy, 21 without STS and 17 with STS. STS reduced the total exposure to diethyldithiocarbamate-reactive CDDP for the peritoneal cavity and plasma by 36% and 25%, respectively. When given alone, CDDP caused a statistically significant acute reduction in creatinine clearance levels; this reduction was less evident when STS was given. We conclude that, whereas STS does reduce systemic exposure, the magnitude of this effect was not sufficient to account for the ability of STS to protect against high-dose CDDP.

Cisplatin↗
PubMed1989

Identification, synthesis and immunogenicity of cuticular collagens from the filarial nematodes Brugia malayi and Brugia pahangi.

The major structural proteins of the cuticle of the filarial nematode parasites Brugia malayi and Brugia pahangi were identified by extrinsic iodination and sensitivity to clostridial collagenase. At least 16 acidic components were identified in adult worms by 2-dimensional electrophoresis, with molecular weights ranging from 35,000 to 160,000. These proteins appear to be cross-linked by disulphide bonds, and localised in the basal and inner cortical layers of the cuticle. The outer cortex, containing the epicuticle, is insoluble in 1% sodium dodecyl sulphate and 5% 2-mercaptoethanol, and can be isolated free of cellular material. Despite their inaccessibility to the immune system in intact worms, antibodies to the cuticular collagens are provoked in humans infected with a variety of filarial parasites. Immunological cross-reactivity was demonstrated between a 35 kDa component and human type IV (basement membrane) collagen. Autoantibodies to type IV collagen were detected in a number of individuals with lymphatic filariasis, although no correlation could be drawn with observed pathology. Synthesis of cuticular collagens is discontinuous, occurs at negligible levels in mature adult male worms, and does not appear to involve the production of small molecular weight precursors, in contrast to Caenorhabditis elegans. Hybridisation with a heterologous cDNA probe coding for the alpha 2 chain of chicken type 1 collagen suggests that they are encoded by a multigene family.

Animals↗
PubMed1989

Predicted structure of a major Schistosoma mansoni eggshell protein.

The complete sequence for a major Schistosome mansoni eggshell protein gene has been determined from a genomic DNA fragment. The use of an open reading frame encoding a glycine-rich polypeptide was confirmed by in vitro translation of schistosome mRNA in the presence of [3H]glycine and comparison with the amino acid composition of purified, schistosome eggshells. Apart from the extraordinary abundance of glycine and tyrosine which are evenly distributed throughout the polypeptide chain, the most striking features of the deduced amino acid sequence are the presence of five well-conserved tandem repeats of 16-18 residues in the N-terminal region and the asymmetrical distribution of charged residues. Acidic residues (Asp) are confined to the N-terminal region, while basic residues (Lys, His), with the exception of a single histidine, are found in the C-terminal region. A model structure composed of short anti-parallel beta-strands is proposed, in which glycines and residues with small side chains lie within the strands and tyrosines and cysteines are arranged at the bends, where they would be available for cross-linking. Four such strands form one of the tandem repeats which are predicted in turn to form a stack of five closely packed beta-sheets, each of three strands and linked by the more variable fourth strand. The C-terminal region may form a similar but less compact structure. The ordered structure demonstrated by birefringence studies of the schistosome eggshell [Kusel, J. (1970) Parasitology 60, 79-88] could be formed by packing of the polypeptides such that the N-terminal domain contributes counter ions or cross-links to the C-terminal domain of adjacent molecules.

Amino Acid Sequence↗
PubMed1989

A cDNA clone encoding part of the major 25,000-dalton surface membrane antigen of adult Schistosoma mansoni.

Immunoscreening of an adult Schistosoma mansoni cDNA expression library, using antibodies raised against purified adult worm tegumental surface membranes, identified a recombinant clone containing a 141-bp insert. Antibodies raised against the recombinant antigen bound specifically to the tegument of adult worms and immunoprecipitated the major 25,000-dalton surface membrane antigen as well as a 22,000-dalton nascent polypeptide generated by cell-free translation of adult S. mansoni mRNA. The mature 25,000-dalton antigen was found to be precipitated by antibodies from infected mice, rats and humans.

Amino Acid Sequence↗
PubMed1989

Non-mutability by ultraviolet light in uvrD recB derivatives of Escherichia coli WP2 uvrA is due to inhibition of RecA protein activation.

The deficiency in UV mutagenesis in uvrD3 recB21 strains of E. coli is almost completely overcome by constitutive activation of RecA protein and expression of the SOS system (by recA730 or 43 degrees C treated recA441 lexA71). When SOS was expressed but RecA protein not self-activated (recA441 lexA71 at 30 degrees C), uvrD3 recB21 still reduced UV mutagenesis at low doses. The uvrD3 recB21 combination is therefore inhibiting activation of RecA protein. It is suggested that the DNA unwinding activity of the products of the uvrD and recB genes may be involved in generating single-stranded DNA needed to activate RecA protein both for the cleavage of LexA repressor and for a further role in UV mutagenesis.

DNA Repair↗