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Biomedical subjects

C Kelly

Publications and source records attributed to C Kelly.

At least 199 records · Page 11Linked to original sources
PubMed1989

DNA binding proteins of Schistosoma mansoni recognizing a hexanucleotide motif occurring in genes regulated by steroids.

1. Schistosome proteins interacting with a gene (F-10), which is only expressed in adult females, were investigated. 2. These were also tested using a synthetic oligonucleotide of 20 bp bearing a defined sequence derived from the F-10 gene and containing a hexanucleotide motif, TGTCCT, occurring in genes responsive to steroids. 3. Schistosome proteins (male and female) bound to the F-10 DNA, but only the male proteins bound to the synthetic oligonucleotide with high affinity. 4. The other preparations each produced different binding patterns, although this seemed to lack specificity. 5. These results indicated that the F-10 gene binds different proteins along its structure and suggested that proteins present in the male schistosomes may regulate its expression.

Animals↗
PubMed1989

The effect of filtration on absolute and differential cell counts in fluid obtained at bronchoalveolar lavage.

We have studied the effects of filtering mucus from bronchoalveolar lavage (BAL) fluid on its cellular contents. We examined BAL fluid from 18 patients without excessive endobronchial mucus, and from three patients with bronchiectasis. In the non-bronchiectatic subjects there was a fall of 18% in mean absolute cell count from 2.66 +/- SD 1.9 x 10(9) l-1 to 2.18 +/- 1.4 x 10(9) l-1 (P less than 0.05) as a result of filtration. This was due to a selective loss of macrophages and there were no significant changes in the absolute numbers of either lymphocytes or neutrophils. The differential macrophage count fell from a mean of 82 +/- 14% to 76 +/- 16%, while the mean differential lymphocyte count rose from 14 +/- 7% to 19 +/- 9% and the mean differential neutrophil count increased slightly from 4 +/- 4% to 5 +/- 4%. In the three patients with bronchiectasis the absolute cell counts were grossly raised, due almost entirely to an excess of neutrophils. In these patients, filtration reduced the absolute macrophage count by 61% and the absolute neutrophil count by 27%. Overall, change in absolute cell count correlated significantly with mucus volume (r = 0.76, P less than 0.05). Removal of mucus by filtration affects absolute cell count and may have a selective effect on cell numbers. If filtration of BAL fluid is unavoidable, its effect on cell counts should be clearly established if data from different centres are to be meaningfully compared.

Adult↗
PubMed1989

Exercise testing soon after myocardial infarction: its relation to course and outcome at one year in patients aged less than 55 years.

A consecutive series of 184 patients aged less than 55 years who had an acute myocardial infarction were enrolled in a study to examine outcome at one year. One hundred of these patients underwent a maximal exercise test six weeks after infarction to evaluate its ability to predict cardiac events. The in-hospital mortality for the series was 7.6% (14 deaths) and the one year mortality for the 170 survivors was 3.8% (seven deaths). During the exercise test 31 patients had angina and 21 had ST depression. During the one year follow up period 39 of 100 patients had angina on exertion, 15 patients underwent coronary artery surgery, three patients had a reinfarction, and one patient died. Angina during the exercise test but not ST segment depression during the exercise test predicted angina on exertion and the need for coronary artery surgery. In the year of follow up angina occurred during everyday exertion in 25 (81%) (95% confidence interval 62 to 92%) of the 31 patients who developed angina during the exercise test and in only 14 (20%) (95% confidence interval 12 to 32%) of 69 patients who did not, and coronary artery surgery was performed in 11 (35%) (95% confidence interval 19 to 54%) of the 31 patients with angina during the exercise test and only four (6%) (95% confidence interval 2 to 15%) of 69 patients without angina. The outcome after myocardial infarction in patients aged less than 55 years was good and the occurrence of angina, but not ST segment depression, during a maximal exercise test six weeks after infarction was an indication for further investigation.

Age Factors↗
PubMed1988

New actinomycin D analogues as superior chemotherapeutic agents against primary and advanced colon tumors and colon xenografts in nude mice.

"Reverse" analogues (RAD's) of actinomycin D (AMD) and their antitumor activity against mouse and human colon tumor cells are reported. RAD's are tetracyclic, and they have an oxazole ring fused on the tricyclic phenoxazine chromophore of AMD. The oxazole ring in RAD is substituted at the C-2 carbon with either a CH3 (in RAD I), a C6H5 (in RAD II), or a CH2CONH(CH2)4NH2 (in RAD III) group. In tumor cells and rat hepatic microsomes, RAD's are metabolized to a tricyclic "symmetrical" analogue of AMD (SAD) with the loss of the oxazole ring and its substituents. RAD and SAD are very active in priming superoxides in the presence of microsomal enzymes as well as in inhibiting the synthesis of DNA and the growth of human colon tumor HT-29 cells in vitro. RAD III and SAD efficiently cleave closed circular plasmid pBR322 DNA like the antitumor agent bleomycin. In addition to their strong inhibitory activity against P388 and B16 tumors in vitro and in vivo, RAD III and SAD demonstrate high levels of activity against primary C26 and advanced C38 colon tumors in mice and against a xenograft of human colon adenocarcinoma CX-1 in athymic mice. In all these biological activities, the analogues demonstrate superiority to AMD in several experimental tumors. Also, the analogues, in contrast to AMD, show reduced toxicity in tumor-free mice, which is possibly due to the metabolic deactivation of SAD in host organs.

Animals↗
PubMed1988

An assessment of methacholine inhalation tests in elderly asthmatics.

We have assessed the feasibility and value of measuring nonspecific bronchial responsiveness to methacholine in investigation of asthma in the elderly. Results from duplicated tests in 20 subjects aged 65-82 years were expressed as dose provoking a 20% decrement in 1 second forced expiratory volume (PD20.FEV1) or peak expiratory flow (PD20.PEF). Repeatability for PD20.FEV1 was satisfactory but less good than in younger subjects, 95% confidence limits being 0.39-2.57 and 0.52-1.91, respectively, x initial PD20. For PD20.PEF, confidence limits were wider (0.26-3.91 x initial PD20) but multiple PEF measurements were better tolerated than those of FEV1, which commonly caused fatigue and dizziness. PD20.FEV1 and PD20.PEF correlated closely (r = 0.95, P less than 0.0001) and both predicted bronchodilatation following a 6-week course of inhaled corticosteroid and beta agonist. This was not predicted by the response to a single dose of beta agonist. We conclude that measurement of bronchial responsiveness is feasible and clinically valuable in elderly subjects.

Aged↗
PubMed1988

Reversal of histamine-induced bronchoconstriction by the H1-receptor antagonist levocabastine: a potential model for efficacy in anaphylaxis.

1. The rate of onset and magnitude of the effect of levocabastine, a potent H1-receptor antagonist, in reversing histamine-induced bronchoconstriction were determined in a double-blind cross-over trial against saline placebo. Histamine was administered by nebuliser so that forced expiratory volume in 1 second (FEV1) was reduced to 80-75% of baseline FEV1 in 10 men with mildly or moderately responsive airways and the effects of intravenous injection of saline or saline + 200 micrograms levocabastine were studied. 2. The maximum rate of recovery of FEV1 was 7[2-10]% min-1 (median [range]) in the first 5 min after levocabastine injection, but only 4[1-7]% min-1 after saline alone (P less than 0.05). 3. The median area under the recovery curve of FEV1 from 0 to 30 min after injection was 405 [228-498]% basal FEV1 X min after levocabastine and 301[98-502]% basal FEV1 X min after saline alone (P less than 0.002). 4. FEV1 returned to 90% of baseline within 30 min in all subjects after levocabastine, but not after saline alone (P less than 0.002). 5. Histamine-induced bronchoconstriction was relieved more quickly by levocabastine than saline alone. This model may have application to the study of drugs used in the treatment of anaphylaxis.

Adult↗
PubMed1988

Breast lumps: rare presentation of oat cell carcinoma of lung.

Two cases of oat cell carcinoma are described. Both patients presented initially with a lump in the breast. A review of the published reports on breast metastases as a presenting feature of malignant disease was performed and lung cancer was found to be the commonest extramammary tumour to present as a breast mass (80% of cases) and usually as small cell carcinoma.

Adult↗
PubMed1988

Number and activity of inflammatory cells in bronchoalveolar lavage fluid in asthma and their relation to airway responsiveness.

Bronchial responsiveness to inhaled methacholine was measured four to six days before fibreoptic bronchoscopy in 22 asthmatic patients (10 smokers) and 20 control subjects (12 smokers). The asthmatic patients had a baseline FEV1 greater than 60% predicted and a PD20FEV1 (provocative dose of methacholine causing a 20% fall in FEV1) of 0.006-3.7 mg. The 20 control subjects had normal pulmonary function and a PD20FEV1 above the maximum cumulative dose of methacholine of 6.4 mg. Bronchoalveolar lavage of a middle lobe segment (lingula in four subjects) was performed with three sequential 60 ml aliquots of sterile saline. Cellular metabolic activity was stimulated with latex in aliquots of resuspended cells, and measured by means of luminol enhanced chemiluminescence to assess neutrophil activity and lucigenin enhanced chemiluminescence to assess macrophage activity. Mean absolute total cell counts were similar in the asthmatic and control groups but there were differences in differential cell counts, with a significant increase in eosinophil (p less than 0.05) and lymphocyte (p less than 0.005) counts in asthma. PD20FEV1 was negatively correlated with percentage neutrophil counts (p less than 0.005). Luminol enhanced chemiluminescence/1000 neutrophils was increased about twofold in asthmatic subjects (p less than 0.001), but was not correlated with PD20FEV1 Lucigenin enhanced chemiluminescence/1000 macrophages was increased nearly fourfold in asthmatic patients (p less than 0.001) and showed a negative correlation with PD20FEV1 (p less than 0.01). The macrophage count was increased twofold in current smokers in both groups, but other cell numbers were not altered significantly. Smoking did not affect cellular metabolic activity in either group. This study supports the idea that an inflammatory process is present in the airways of those with asthma, and suggests a relation between bronchial responsiveness and both neutrophil numbers and macrophage activity.

Adolescent↗
PubMed1988

The effect of bronchoalveolar lavage on bronchial responsiveness in patients with airflow obstruction.

This study assessed the effect of bronchoalveolar lavage (BAL) on nonspecific bronchial responsiveness in 31 patients. Of these, 20 had airflow obstruction; 11 control subjects had normal pulmonary function. Bronchial responsiveness to methacholine, expressed as the dose of inhaled methacholine required to provoke a 20 percent fall in forced expiratory volume in one second (PD20 FEV1), was measured before and after BAL. We found no evidence for the induction of responsiveness by BAL in 11 control subjects with negative methacholine tests prior to the procedure. There were small but significant falls in FEV1 following BAL in both the control group and in patients with airflow obstruction. Thus, BAL does not appear to induce nonspecific bronchial hyperresponsiveness in subjects without airflow obstruction, nor does it affect airway responsiveness in emphysema patients. Among asthmatics, bronchial responsiveness can be increased as a result of BAL; this increase was greatest in patients who were most responsive initially.

Adolescent↗
PubMed1987

AIDS and renal failure.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Characterisation of the structure and expression of the gene encoding a major female specific polypeptide of Schistosoma mansoni.

A previously described cDNA clone, pSF10, of Schistosoma mansoni encoding the very dominant female specific polypeptide (FSP) has been used to characterize the gene and its expression. The gene is detectable in different isolates of S. mansoni and is estimated to be present in 3 copies per haploid genome. The gene is not sex linked and exhibits neither amplification nor rearrangement concomitant with expression. Expression of the gene by parasites maturing in hamsters is first detected after 5 weeks when the RNA is present at 1/10 the level of that of 6 week worms. Although the FSP gene is specifically and highly expressed by egg laying female worms a corresponding polypeptide produced by the cell-free translation of RNA is not detectable. It was confirmed, however, that pSF10 does indeed encode a mRNA by DNA sequence analysis. The sequence demonstrated a mRNA containing a poly(A) tail and two open reading frames. One reading contains no methionine but is very high (47%) in glycine. This amino acid composition could account for the inability to detect the gene product by cell-free translation in the presence of [35S]methionine.

Animals↗
PubMed1987

Resistance to reinfection with Schistosoma haematobium in Gambian children: analysis of their immune responses.

The relationship between reinfection with Schistosoma haematobium and immunological parameters was studied in a group of Gambian children aged from 8 to 13 years. Each individual's exposure to infection was assessed from observations of water contact, cercarial densities and infected snail densities at water contact sites. Eosinophil counts were made and responses to egg antigen (SEA) and adult worm antigen (WWH) measured by ELISA. Low levels of reinfection were associated with a high eosinophil count, high levels of antibodies against WWH and SEA, increased age and low exposure. In a multiple regression analysis of the association of reinfection with eosinophil count, antibody levels, exposure, age and sex, the effects of eosinophil count and exposure were still very significant after allowing for all the other variables. The effects of the antibody levels were close to significance after allowance for exposure and eosinophil count (for WWH: P = 0.09; for SEA: P = 0.07), although the evidence was less clear after additional allowance was made for age and sex. The ability of sera from the children to recognize different parasite antigens was also examined by immunoprecipitation of labelled schistosomulum surface, WWH, SEA and S. haematobium adult worm mRNA in vitro translation products. Schistosomulum surface antigens were recognized by all the sera and there was little variation in this response. There was more variation in their responses to SEA and WWH and a marked heterogeneity in the response to in vitro translation products. However, the pattern of antigen recognition appeared unrelated to susceptibility to reinfection.

Adolescent↗