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Biomedical subjects

P Ferguson

Publications and source records attributed to P Ferguson.

At least 19 recordsLinked to original sources

Linkage of a microsatellite marker to the canine copper toxicosis locus in Bedlington terriers.

OBJECTIVE: To identify a DNA marker for the copper toxicosis (CT) locus in Bedlington Terriers (BT). ANIMALS: 77 BT, of which 25 were affected. Diagnosis of affected or unaffected with CT was made in all cases by quantitative copper determinations on liver biopsy samples by use of established criteria. PROCEDURE: BT pedigrees segregating for CT were identified. Linkage studies were carried out using polymorphic microsatellite markers developed for the canine genome in these pedigrees. DNA was isolated from blood samples of pedigree members. Polymerase chain reaction was used to amplify and type alleles at 213 microsatellite loci in each dog, and findings were subjected to linkage analysis. RESULTS: One microsatellite marker was identified to be closely linked to CT with logarithm of odds score of 5.96 at a recombination fraction of zero. CONCLUSIONS: Using the linked marker, it has become possible to distinguish affected, homozygous normal, and carrier dogs in some BT pedigrees. CLINICAL RELEVANCE: In informative pedigrees where the marker is variable in the parents, it is possible to identify which dogs will require anticopper therapy and provide breeders with sound scientific advice about breeding strategies.

Alleles

Effects of theophylline and ipratropium on cognition in elderly patients with chronic obstructive pulmonary disease.

OBJECTIVES: To determine whether chronic therapy with theophylline or ipratropium has an adverse effect on cognition and psychomotor skills in geriatric patients with chronic obstructive pulmonary disease. DESIGN: The study design was a randomized, repeated measures, double-blind, double-dummy, placebo-controlled comparison of theophylline and ipratropium treatments. SETTING: Ambulatory patients were tested at the Clinical Trials Center of the University of California, San Diego, Medical Center. PATIENTS: Ambulatory patients with chronic obstructive pulmonary disease aged 65 years or more with FEV1 less than 60% predicted, FEV1/FVC less than 70%, and post bronchodilator FEV1 less than 70%. INTERVENTIONS: Patients received either theophylline or ipratropium for 2 weeks, followed by a 1-week placebo control period, then a 2-week treatment period of the alternative drug therapy. A standard therapy of albuterol MDI, 2 puffs (180 microg) qid was given throughout the study. MEASUREMENTS: The main response level was an 11-part battery of psychometric tests. Tests were administered at the end of each treatment period and at the end of the washout period. Covariates were sequence of treatment, pulmonary function tests, age, and baseline psychometric test scores. RESULTS: There was no difference in performance scores on the cognitive tests among the three treatment periods. CONCLUSIONS: We were unable to detect a harmful effect of treatment with either theophylline or ipratropium on the performance of elderly patients with chronic obstructive pulmonary disease on a battery of psychometric tests, suggesting that significant cognitive impairment in the elderly is not commonly associated with treatment with either theophylline or ipratropium.

Aged

Environmental and bronchoalveolar lavage Dermatophagoides pteronyssinus antigen levels in atopic asthmatics.

Overnight environmental home exposure to Dermatophagoides pteronyssinus in IgE-sensitized individuals is often clinically associated with increased morning symptoms of rhinitis and/or asthma. We have investigated whether household exposure to D. pteronyssinus is associated with the presence of immunoreactive D. pteronyssinus I antigen (Der p I) in bronchoalveolar lavage (BAL) fluid in nine atopic asthmatics sensitized to D. pteronyssinus. Significant environmental concentrations of D. pteronyssinus were noted by light microscopy and immunoassay in the subjects' bedroom carpets (13.4 +/- 3.8 micrograms immunoreactive Der p I/g dust), mattresses (27.3 +/- 7.2 micrograms immunoreactive Der p I/g dust), and living room carpets (5.9 +/- 1.5 micrograms immunoreactive Der p I/g dust). Immunoreactive Der p I was measurable in 20-fold concentrated BAL fluids (3.4 +/- 1.0 ng/ml concentrated BAL fluid) after overnight home exposure. A 24-h hospitalization in a D. pteronyssinus controlled environment (< 0.02 micrograms Der p I/g dust) resulted in a significant decrease in BAL Der p I concentrations (0.8 +/- 0.6 ng/ml). In vivo studies in nine asthmatics challenged endobronchially with D. pteronyssinus (5-60 ng Der p I) induced significant airway eosinophilia. These studies demonstrate that environmental exposure to microgram amounts of D. pteronyssinus is associated with airway recovery of small nanogram amounts of Der p I.

Adult

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Female

Airway levels of mast cell-derived mediators in exercise-induced asthma.

In order to assess the role of mast cell-derived mediators in the pathogenesis of exercise-induced asthma (EIA), we completed pre- and postexercise bronchoalveolar lavage (BAL) in seven atopic subjects with EIA. The study subjects were defined as having EIA if they exhibited a greater than 15% decrease in FEV1 after completing 6 min of treadmill exercise. There were no significant differences between mean preexercise and mean postexercise mast cell-derived BAL histamine (186 +/- 67 versus 148 +/- 36 pg/ml), tryptase (4.5 +/- 2.0 versus 2.8 +/- 2.0 ng/ml), prostaglandin D2 (26 +/- 11 versus 32 +/- 25 pg/ml), or leukotriene C4 (less than 100 versus less than 100 pg/ml). In addition, mast cells present in BAL fluid after exercise contained similar amounts of cellular histamine compared with BAL mast cells obtained before exercise (preexercise BAL cellular histamine, 26.6 +/- 12.3 ng/10(6) BAL cells; postexercise BAL cellular histamine, 22.7 +/- 9.1 ng/10(6) BAL cells), indicating that depletion of preformed mast cell mediators are unlikely to account for the refractory period in EIA. This study suggests that the cellular pathogenesis of EIA (mast cell-independent) differs from current theories of the pathogenesis of extrinsic allergen-induced asthma (mast cell-dependent).

Adolescent

Long-term prognosis after repair of double-chamber right ventricle with ventricular septal defect.

To determine long-term postoperative results in patients with double-chamber right ventricle and ventricular septal defect, 20 patients who had survived complete repair between 1959 and 1966 were recalled and studied. An interview, physical examination, electrocardiogram and chest x-ray were performed in all 20 patients, a treadmill exercise test in 16, 24-hour Holter monitor recording in 7 and postoperative cardiac catheterization in 8. Mean age at repair was 14 years and at follow-up evaluation 33 years. There were no late deaths. At a mean follow-up of 19 years, 17 patients were in New York Heart Association functional class I, 1 patient was in class II and 2 patients were in class III. Reoperation was performed in 2 patients (10%), and at present only 1 patient (5%) is considered to have hemodynamically significant cardiac compromise. Aortic regurgitation, not present in any patient preoperatively, developed in 5 patients (25%). Mild residual right ventricular outflow obstruction was present in 2 (10%) and the murmur of a hemodynamically insignificant residual ventricular septal defect or tricuspid regurgitation was present in 5 patients (25%). One patient (5%) had cardiomegaly (cardiothoracic ratio greater than 0.55). The frequency of infective endocarditis in the postoperative follow-up period was 1 per 388 patient-years. Thus, 20 years after repair of double-chamber right ventricle, mild residua and sequelae are common, but serious cardiac compromise is infrequent.

Adolescent

Long-term prognosis (15 to 26 years) after repair of tetralogy of Fallot: I. Survival and symptomatic status.

One hundred eighty-two patients with tetralogy of Fallot repaired before or during 1967 were studied by interview, physical examination, and noninvasive testing. Twenty were excluded from the final analysis because review of cineangiograms and operative reports disclosed that they had had double-chambered right ventricle rather than tetralogy of Fallot. On follow-up ranging from 15 to 26 years (mean, 20.2 years), there were 86 patients in New York Heart Association Functional Class I, 53 in Class II, 5 in Class III, and none in Class IV. There were 9 late deaths. Functional classification was not ascertained in the remaining 9 patients. Cumulative survival at 25 years postoperatively was 94.4%. There was no significant relationship between survival and year of operation, age at operation, sex, or presence of a prior shunt. The 9 late deaths occurred between 6 and 23 years after operation and were due to late-onset complete heart block in 2 patients, congestive failure in 4, suicide in 1, accident in 1, and an unknown cause in 1. We conclude that long-term survival after repair of tetralogy of Fallot is excellent and not influenced by prior shunt.

Adolescent

Increased sulphation level and altered composition of glycosaminoglycans synthesized by cultured smooth muscle cells in the presence of beta-D-xylosides.

Cultured rat and bovine smooth muscle cells incorporated more 35SO4 into macromolecular glycosaminoglycans in the presence of beta-D-xylosides than in their absence. More than 90% of the xyloside-initiated glycosaminoglycans were secreted rapidly into the culture medium and were more highly sulphated than glycosaminoglycans polymerized on core protein. The increased extents of sulphation were associated with increased synthesis of dermatan sulphate and a decrease in that of nitrous acid-sensitive glycosaminoglycans.

Animals

Effects of age, gender, and cigarette smoking on human immunoregulatory T-cell subsets: establishment of normal ranges and comparison with patients with colorectal cancer and multiple sclerosis.

Normal ranges for peripheral circulating mature functional T cells (OKT3+), T helper-inducer cells (OKT4+), and T cytotoxic-suppressor cells (OKT8+) were determined in 161 normal male and female volunteers. Children between 5 and 15 years of age showed higher circulating OKT3+ cell numbers than adults, and in male children the circulating OKT4+ cell number was also higher. In adults, females demonstrated higher circulating OKT4+ cell numbers than males, and smokers demonstrated higher circulating numbers of both OKT3+ and OKT4+ cells than nonsmokers. There was a significant interaction between gender and smoking, with female smokers exhibiting the highest circulating OKT3+ cell numbers. Two groups of patients entering longitudinal T-cell subset monitoring studies were compared to their appropriate normal control groups. It was found that 48% of patients with colorectal cancer were T-cell (OKT3+) lymphopenic at presentation, and that 62% had a low OKT4/OKT8 ratio. Colorectal surgery tended to correct this T-cell lymphopenia. However, only transient rises in low OKT4/OKT8 ratios were observed after surgery. Of 11 patients with multiple sclerosis in a trial of transfer factor therapy, 7 were found to have high OKT4/OKT8 ratios prior to treatment; these ratios have persisted to date during treatment.

Adolescent

Carcinoma-associated cytostructural antigenic alterations: detection by lectin binding.

Tumor cell membrane glycoproteins may be involved in the induction of tumor immunity or in the escape of tumors from immunologic defense mechanisms. Previous investigations have suggested a role for blood group antigens and their precursors, in the generation of the immune response to neoplasia. In this study, 44 benign and malignant breast lesions were examined for the presence of a carbohydrate precursor antigen (T-antigen) of the human blood group system MN. T-antigen was demonstrated using an immunohistochemical technique to detect tissue binding of a plant lectin (PNA) with specificity for T-antigen. Of the 22 benign breast lesions examined, 19 showed T-antigen present along the luminal cytoplasmic membrane and occasionally on intraluminal secretions. T-antigen, as demonstrated by lectin binding, was confined to this region in all benign lesions except one, which also showed cytoplasmic positivity. Malignant breast lesions showed a pattern of T-antigen expression markedly different from that of benign breast tissues. Of 22 breast carcinomas, 17 showed diffuse cytoplasmic T-antigen. Five carcinomas showed no evidence of T-antigen by this technique. These malignancies tended to be the most poorly differentiated when judged by histologic criteria. A possible role for T-antigen in the modulation of the immune response to breast carcinoma is suggested.

Antigens, Neoplasm