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Biomedical subjects

C A Kelly

Publications and source records attributed to C A Kelly.

At least 19 recordsLinked to original sources
PubMed1992

Paraproteins in rheumatoid arthritis and related disorders.

There is evidence that the prevalence of monoclonal parparoteinaemia is slightly increased in patients with rheumatoid arthritis. The possibility that this may be a marker of the development of later malignancy in such patients is explored. Mortality rates in rheumatoid arthritis are increased although the development of lymphoreticular malignancy contributes only a small percentage of this increase. However, it does seem likely that patients with longstanding severe rheumatoid arthritis are more at risk of developing myeloma or lymphoma if they have a monoclonal paraprotein band in their serum. IgA paraprotein seems to carry a higher risk than IgG whilst other factors such as urinary free light chains and the presence of secondary Sjögren's syndrome are of less prognostic significance. Similarly a monoclonal paraprotein may identify patients with primary Sjögren's syndrome who have a particular risk of later lymphoma whilst this risk does not appear to extend to patients with systemic lupus erythematosus. Patients with an overlap syndrome do not appear to be at greater risk than those with "pure disease". The association of other rheumatological disease and paraproteinaemia is briefly discussed.

Arthritis, Rheumatoid↗
PubMed1992

Levels of CD5+ B cells are not increased in probands or relatives in a family study of primary Sjögren's syndrome.

Levels of CD5+ B lymphocytes were assayed in a large family study of Primary Sjögren's syndrome. There was no significant difference in CD5 expression by index cases or their relatives when compared to controls. No association between CD5 expression, serological abnormalities or HLA haplotype was found and, furthermore, no evidence of linkage with HLA was observed. There was, however, variation in the expression of CD5+ B cells between the families. Levels in spouses were lower and reached statistical significance. The role for genetic and environmental factors influencing CD5 expression is discussed. Any genetic influence does not appear to involve the HLA region or genes in linkage disequilibrium.

Adult↗
PubMed1991

Preliminary X-ray diffraction analysis of a crystallizable mutant of malate dehydrogenase from the thermophile Thermus flavus.

Malate dehydrogenase from mutant strain F428 of the thermophilic bacterium Thermus flavus has now been crystallized from polyethylene glycol 8000 in a form suitable for diffraction studies. The protein crystallizes in the orthorhombic P2(1)2(1)2(1) space group with unit cell dimensions a = 71.8 A, b = 88.6 A, c = 119.0 A. The asymmetric unit consists of one homodimer of molecular mass 67,000 Da. The X-ray diffraction extends beyond 1.7 A and a full data set to 1.9 A has been collected.

Crystallization↗
PubMed1991

Primary Sjögren's syndrome in north east England--a longitudinal study.

We have documented the initial clinical features of 100 patients with primary Sjögren's syndrome (SS) together with the results of their baseline investigations. The evolution of the disease in these patients has been followed for a median of 34 months (range 3-84 months). The majority of patients were females aged 40-60 years, and common clinical features included eye symptoms (100%), xerostomia (100%), polyarthralgia (94%), Raynaud's phenomenon (81%) and salivary gland swelling (47%). Thyroid disease was relatively common (14%) while other endocrine disease was rare. Four patients died during follow-up, and three cases of lymphoma were detected. Other serious complications included pericarditis (10%), pleuroparenchymal lung disease (9%), renal tubular acidosis (3%) and cerebrovascular accidents (2%). The presence of anti-Ro antibodies identifies patients with more severe systemic disease. Spontaneous improvement occurred in 12 patients, while steroids were required for specific complications in 18. Overall, although lymphoma was found to excess in our group, the high mortality reported with primary SS elsewhere was not seen.

Adolescent↗
PubMed1990

Amino acid sequences of ovomucoid third domain from 25 additional species of birds.

Ovomucoids were isolated from 25 avian species other than the 101 studied in Laskowski et al. (1987, Biochemistry 26, 202-221). These were subjected to limited proteolysis with an appropriate enzyme, and connecting peptide extended ovomucoid third domains were isolated and sequenced to the end in a protein sequencer. Of the 25 new sequences, 13 duplicate ones were already known, and 12 are unique. Probably the most striking findings are a Pro14----Ser14 replacement in weka, an Ala14----Thr15 replacement in Bulwer's pheasant, the discovery of two additional amino acid residues Ile18 and Gly18 at the P1 reactive site position in Kalij pheasant and tawny frogmouth, respectively, and the first finding of a negative (Glu34) rather than positive (Lys34 or Arg34) amino acid residue at the NH2 terminus of the alpha helix in caracara ovomucoid third domain. These results complete the determination of all the sequences of ovomucoid third domains in the four species genus Gallus, in the five species genus Syrmaticus, and in the two species genera Aix and Pavo.

Amino Acid Sequence↗
PubMed1990

The reversible effect of lignocaine on the stimulated metabolic activity of bronchoalveolar lavage cells.

Lignocaine concentrations were measured in the aspirate from a low volume (100 ml) bronchoalveolar lavage (BAL) in twenty patients who had received topical 4% lignocaine as required, and compared to those found in the aspirate from a 180 ml BAL in ten patients who had received 1.5% isotonic lignocaine. The median BAL supernatant lignocaine concentration was significantly lower at 0.14 mM (range 0.07-0.44 mM) in the group who received 1.5% lignocaine, compared to 1.08 mM (range 0.03-7.05 mM) in those given 4% lignocaine (p less than 0.01). The effect of increasing concentrations of lignocaine on BAL neutrophil and pulmonary macrophage metabolic activity, as assessed by latex-stimulated luminol- and lucigenin-amplified chemiluminescence (CL), respectively, in mixed BAL cell populations, were measured following preincubation of "washed" harvested BAL cells with 0.4-8.0 mM lignocaine. There was no demonstrable decline in either cell activity with lignocaine concentrations of up to 2 mM, with dose-dependent inhibition of both above this threshold. Cell viability was unaffected. In a further experiment, the inhibition induced by 8 mM lignocaine on both pulmonary macrophage (lucigenin-amplified CL of harvested BAL cells) and isolated peripheral blood neutrophil metabolic activity was completely reversed by a single "wash", following both 30 and 60 min incubations at 4 degrees C, which was equivalent to resuspending harvested BAL cells in fresh medium after separation from BAL supernatant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

The relative contribution of bronchoalveolar macrophages and neutrophils to lucigenin- and luminol-amplified chemiluminescence.

The relationship between differential cell counts and latex-stimulated luminol and lucigenin-amplified chemiluminescence (CL) was investigated by mixing alveolar macrophages (AM) obtained at bronchoalveolar lavage (BAL) with allogeneic peripheral blood neutrophils (PMN) in varying proportions. In 5 non-asthmatic subjects, the mean luminol-amplified CL increased linearly from 2.1 (0.9 SEM) x 10(5) counts per second (cps) with less than 2% PMN, greater than 96% AM to 47.3 (11.1 SEM) x 10(5) cps with greater than 94% PMN, 0% AM (r = 0.996, p less than 0.001). The regression had a y-intercept indistinguishable from 0 cps, suggesting that luminol-amplified CL exclusively reflected PMN activity. Using the same technique, the mean lucigenin-amplified CL showed a fall from 35 (2.3 SEM) x 10(5) cps with a cell population of greater than 96% AM, less than 2% PMN to 20 (2.3 SEM) x 10(5) cps with 0% AM, greater than 94% PMN. Both PMN and AM appeared to contribute to lucigenin-amplified CL, with AM contributing approximately 1.7 times as much activity per cell as PMN. Lucigenin-amplified CL appeared to be an appropriate technique for measuring AM activity when the proportion of PMN in mixed cell populations was small. A linear relationship was found between percent PMN count and luminol-amplified CL measured in a mixed BAL cell population from asthmatic subjects (p less than 0.01) and non-asthmatic controls (p less than 0.01). The slope of this regression line was significantly greater for subjects with asthma than for control subjects (p less than 0.01), suggesting a uniform increase in PMN activity in cells obtained from asthmatic airways.

Acridines↗
PubMed1990

Platelet-activating factor in bronchoalveolar lavage fluid from asthmatic subjects.

Bronchoalveolar lavage (BAL) was performed on 28 asthma patients, 7 patients with emphysema and 11 control subjects. Total and differential cell counts were performed and cellular metabolic activity was assessed using luminol and lucigenin amplified chemiluminescence. BAL supernatants were assayed for platelet-activating factor (PAF) and lyso-PAF using a sensitive guinea-pig bioassay. Eight of the asthma patients but none of the emphysema patients or control subjects had PAF in their BAL fluid. Lyso-PAF was measurable in BAL fluid in most subjects and no differences were detected between groups. Among the asthma patients, the presence of PAF in BAL supernatant was significantly associated with a combination of low neutrophil and high lymphocyte counts (p less than 0.05) and with macrophage metabolic activity as assessed by lucigenin chemiluminescence (p less than 0.05).

Adolescent↗
PubMed1990

Chronic pericardial disease in patients with rheumatoid arthritis: a longitudinal study.

We have reviewed the clinical and investigative findings in 13 patients with chronic pericardial disease and seropositive rheumatoid arthritis. In eleven cases the diagnosis was made on clinical grounds, while the diagnosis was confirmed only at post-mortem in two patients. Pleural effusions were present in seven patients, while pulsus paradoxus was found in only one case. Echocardiograms were undertaken in ten patients and all showed evidence of pericardial effusions, which were usually small and sited posteriorly. A delayed ventricular filling pattern indicating abnormal ventricular relaxation was seen in two patients with cardiac tamponade. The surviving 11 patients were reviewed a median of three years after diagnosis of their pericardial disease. Pericardectomy had been performed in six, all of whom were asymptomatic and had a normal chest radiograph. Steroids alone had been given to the other five, and three of these remained dyspnoeic with cardiomegaly. The clinical features distinguishing chronic pericardial disease from other causes of right heart failure in rheumatoid arthritis patients are subtle. As management is fundamentally different, serious consideration should be given to the diagnosis of chronic pericardial disease in any patient with rheumatoid arthritis who presents with right-sided heart failure.

Adult↗
PubMed1989

Abnormally-fucosylated serum haptoglobins in patients with inflammatory joint disease.

The fucosylation of haptoglobins is altered in rheumatoid arthritis. In order to investigate the clinical usefulness of this finding, serum levels of abnormally-fucosylated haptoglobins (FHp) have been assessed in defined and matched groups of patients with different inflammatory joint diseases. FHp was elevated in 16/17 patients with active rheumatoid arthritis (RA); 1/20 patients with inactive rheumatoid arthritis; 1/11 patients with osteoarthritis; and 4/10 patients with seronegative polyarthritis. Raised FHp levels, therefore, are not disease-specific. There was no relationship between the duration of RA and the FHp level. The FHp expression in RA was also compared with other biochemical indices of disease activity. The degree of correlation between FHp and articular index, joint score and early-morning stiffness was very similar to that obtained for C reactive protein (CRP), and better than that obtained for erythrocyte sedimentation rate and haemoglobin. FHp, however, gives fewer false-positives than CRP in cases of inactive disease. until FHp can be measured more easily and cheaply, CRP estimation is still the biochemical test of choice in RA.

Adult↗
PubMed1989

Cognitive skills associated with the onset of multiword utterances.

The relationship between early language and cognition was studied in 20 children between one and two years of age. Linguistically, the subjects were classified as No Word Users, Single Word Users, Nonproductive Syntax Users, and Productive Syntax Users. Four cognitive areas were tested: Object Permanence, Means-end, Play, and Imitation. When adjacent pairs of linguistic groups were compared in terms of specific cognitive skills demonstrated, several significant differences were found. First, a significant difference in Play was found between No Word Users and Single Word Users. Second, there were significant differences between Single Word Users and Nonproductive Syntax Users in terms of specific cognitive advances in both Imitation and Play. Third, Nonproductive and Productive Syntax Users were significantly different in Means-end skills. In accordance with the Correlational Hypothesis, specific cognitive skills seem temporally associated with some linguistic abilities, although attainment of skills can be evidenced first in language or cognition.

Child Language↗
PubMed1989

Occupational asthma due to a repair process for polyethylene-coated electrical cables.

We report the case of an electrical cable repairer who presented with symptoms suggestive of occupational asthma. A supervised workplace challenge test confirmed this diagnosis and laboratory challenge studies implicated heated polyethylene repair tape containing the chemical cross-linking agent dicumyl peroxide as the cause. Similar cross-linking processes are widely used in the cable manufacturing industry and the possibility of occupational asthma occurring in other settings may need to be considered.

Adult↗
PubMed1989

Lymphocyte subsets in bronchoalveolar lavage fluid obtained from stable asthmatics, and their correlations with bronchial responsiveness.

Bronchial responsiveness to methacholine (PD20 FEV1) was assessed in 22 asthmatic subjects approximately 5 days prior to bronchoalveolar lavage (BAL). A PD20 FEV1 could not be attained in 20 matched controls with normal pulmonary function. BAL was performed in all subjects, 3 x 60 ml aliquots of buffered saline being introduced into a segment of the middle lobe and immediately aspirated into siliconized glassware at 4 degrees C. After filtration, cells were counted, and the cell pellet resuspended in medium 199. Cytospin slides were prepared and a differential cell count performed. Lymphocyte subsets were identified by labelling further cytospin preparations with specific monoclonal antibodies (Leu series) against T3, T4, T8 and B cell markers, followed by a fluorescent antibody marker. The slides were coded, and 100 lymphocytes were then randomly scanned for fluorescence on each cytospin preparation. The median total lymphocyte counts were significantly greater in the asthmatic subjects, but this increase was confined to the T cell subgroups. The mean T4/T8 ratio was similar in asthmatic (1.51) and control (1.45) subjects. Log PD20 FEV1 correlated positively with total lymphocyte counts (r = 0.42, P less than 0.05), and with total T8 counts (r = 0.60, P less than 0.05). Correlations between bronchial responsiveness and T3, T4 and B lymphocyte numbers all failed to reach significance, and there was no correlation with T4/T8 ratios. The increase in BAL lymphocyte counts in asthma appears to be due to an absolute increase in T cell subsets, especially the T8 lymphocyte subgroup, and is most marked in mild asthmatics.

Adolescent↗
PubMed1988

Haematuria in rheumatoid arthritis: a follow up study.

Twenty one patients with seropositive rheumatoid arthritis and previously documented isolated haematuria were recalled at a median 7.7 years (range 3-12) after initial investigation. Eighteen subjects had previously undergone renal biopsy, which had shown mesangial glomerulonephritis in all but four cases. Renal function was found to have remained normal in all patients with previous mesangial changes despite the presence of persistent haematuria in most cases.

Arthritis, Rheumatoid↗
PubMed1988

Assessment of pulmonary macrophage and neutrophil function in sequential bronchoalveolar lavage aspirates in sarcoidosis.

Bronchoalveolar lavage was performed in eight patients with biopsy proved sarcoidosis and eight control subjects matched for age and smoking habit, three sequential 60 ml aliquots of sterile saline being used. Each aliquot was aspirated and analysed separately to determine total and differential cell counts. Cellular metabolic activity was stimulated with latex and measured by means of luminol enhanced chemiluminescence to assess neutrophil activity and lucigenin enhanced chemiluminescence to assess macrophage activity. In control subjects mean total cell counts were significantly greater in the second aspirate than in the first, but fell slightly in the third. Similarly, in the patients with sarcoidosis mean total cell counts increased from aspirate 1 to a maximum in aspirate 2, before falling again marginally in aspirate 3. The only significant difference in cell counts between patients with sarcoidosis and controls was an approximately threefold increase in total lymphocyte counts in the former in each of the three aspirates. Luminol chemiluminescence was similar in patients with sarcoidosis to that in controls in the first aspirate, but was significantly greater in the second and third aspirates. Lucigenin chemiluminescence was also significantly greater in the second and third aspirates only. Thus in patients with sarcoidosis lymphocyte numbers are increased in all three aspirates whereas cellular metabolic activity is increased to a greater extent in later aspirates, which may reflect events occurring in the periphery of the lung segment.

Acridines↗
PubMed1988

Modulation of tight junction formation in clone 4 MDCK cells by fatty acid supplementation.

Clone 4 MDCK cells, which generate a transepithelial electrical resistance (TER) of greater than 2,000 omega.cm2, were used to examine the role of membrane lipids in the barrier function of tight junctions. Phospholipid acyl groups were modified by supplementing cells grown in serum-free medium with 18:1(n-9), 18:3(n-3), or 18:3(n-6) complexed to albumin. Although both of these polyunsaturated fatty acids depress the melting point of membrane phospholipids, only 18:3(n-6) contributes significantly to eicosanoid production. Saturation indices of the phospholipids of cells supplemented with albumin alone, 18:1(n-9), 18:3(n-3), or 18:3(n-6) were 0.77, 0.78, 1.81, and 1.65, respectively. After trypsinization or removal of Ca2+, cells supplemented with 18:3(n-6) required longer periods of time to reestablish TER than did nonsupplemented cells or those incubated with 18:3(n-3) or 18:1(n-9). In contrast to MDCK strains I and II, clone 4 MDCK cells required continuous protein synthesis not only to reseal preexisting junctions after the addition of Ca2+ to Ca2+-depleted monolayers, but also to maintain steady-state TER. The rate of decay of TER in the presence of 1 microgram/ml of cycloheximide was 1.5 times greater in cells supplemented with either of the two 18:3 isomers than it was in nonsupplemented controls or in cells supplemented with 18:1(n-9). No significant difference was observed in the steady-state TER or selectivity of the tight junctions after fatty acid supplementation. These results suggest that there is a change in the dynamics of junction formation, rather than an alteration in their intrinsic properties.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗