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Biomedical subjects

R Evans

Publications and source records attributed to R Evans.

At least 37 records · Page 2Linked to original sources

Immunotherapy in atopic disorders.

Immunotherapy plays an important role in the treatment of allergic rhinitis, asthma, and insect sting allergy. In the latter circumstance, immunotherapy with specific venom from the stinging insects can be life saving. Most commonly employed in immunotherapy are aqueuos extracts of aeroallergens, particularly plant pollen, and mold spores. Recent advances suggest that modification of these allergens, such as polymerization, can result in improved symptom response with fewer side effects. Efficacy trials of immunotherapy have demonstrated satisfactory treatment responses in allergic rhinitis and allergen-induced asthma. These responses, as measured by changes in symptom scores, are attended by specific immunologic changes summarized in Table 2.

Allergens

Oligonucleotides in heterogeneous nuclear RNA: similarity of inverted repeats and RNA from repetitious DNA sites.

A comparison has been made by oligonucleotide analysis of three fractions of HeLa cell hnRNA: (1) the "snap-back" fraction (ds-hnRNA, 5% of the total); (2) the fraction that self-anneals during prolonged incubation (25% of total); and (3) the fraction that hybridizes most rapidly to an excess of HeLa cell DNA (rep-hnRNA, 10% of the total). T1 fingerprints of each of these hnRNA fractions were similar to one another and featured the largest T1 oligonucleotides of known sequence previously isolated from ds-hnRNA (Robertson, H.D., et al. (1977) J. Mol. Biol. 115, 571--590; Jelinek, W. (1977 J. Mol. Biol. 115, 591--602). When hybridized to DNA either in solution or immobilized on filters, the isolated ds-hnRNA and the rep-hnRNA fractions showed similar hybridization kinetics in the COt range of "intermediate" repetitive DNA sequences; the ds-hnRNA and the rep-hnRNA also self-annealed to equal extents in the absence of any DNA. DNA of all buoyant density classes contained the T1 oligonucleotides diagnostic of the ds-hnRNA and the rep-hnRNA. While hnRNA is rich in inverted repeated sequences, cytoplasmic mRNA contains far fewer such sequences.

Base Sequence

Failure to relate the anti-tumour action of cyclophosphamide with the immunogenicity of two murine fibrosarcomas.

A single intraperitoneal injection of cyclophosphamide (CY) had a stronger anti-tumour effect upon two syngeneic mouse fibrosarcomas when given within a few days of tumour implantation than when given 7-20 days after. CY was more active against the fast-growing, relatively non-immunogenic CBA fibrosarcoma, FS13, inducing a higher proportion and permanent regressions, than the slower-growing, highly immunogenic C57BL fibrosarcoma, FS6, at all comparable stages of tumour growth. Whole-body irradiation, which suppressed concomitant immunity in FS6-tumour-bearing mice, had no effect on the anti-tumour action of CY. A study of the cellular composition of the tumour masses over a 4-day period immediately after CY injection showed that there was a decrease in total cell yields, involving mainly a decrease in neoplastic cells, although normal cells, Fc-receptor-positive and -negative, were also affected to a lesser degree. The overall findings indicated a lack of correlation between the anti-tumour effects of CY and tumour immunogenicity. Moreover, it was apparent that the anti-tumour action of CY was mediated by a direct effect of its metabolites on neoplastic cells rather than by host anti-tumour effector mechanisms.

Animals

Evaluation of the adverse effects of long-term hyposensitization.

This study was undertaken to determine if long-term hyposensitization causes late sequelae, particularly those reflecting aberrant immunologic responses. Atopic individuals receiving five or more years of hyposensitization with allergenic extracts showed no increased autoimmune, collagen vascular, or lymphoproliferative disease. In addition, chronic hyposensitization did not have adverse effects on immunologic reactivity as assessed by a number of immune parameters. Particularly noteworthy was the absence of immune complexes in the serum of patients undergoing long-term hyposensitization. This study represents the first systematic investigation of potential adverse effects of long-term hyposensitization.

Adolescent

Blood alcohol concentrations of patients attending an accident and emergency department.

The prevalence of detectable blood alcohol in all new adult patients attending an accident and emergency department was 10.3%. The mean concentration was 20.9 mmol/1 (96 mg/dl). There were significantly more patients with detectable alcohol in the following groups: male patients; patients aged under 35 years; patients attending on Saturdays; patients attending between 21.00 and 08.59 hours; patients involved in road traffic accidents; patients presenting because of drug overdosage, and head injuries. Those with detectable blood alcohol were more likely to be admitted, probably because of their associated reason for attendance. Patients referred by their general practitioner were less likely to have detectable blood alcohol.

Accidents

Lack of correlation between in vivo rejection of syngeneic fibrosarcomas and in vitro non-specific macrophage cytotoxicity.

Two transplantable, highly immunogenic syngeneic C57BL fibrosarcomas, FS1 and FS6, were shown to have tumour-specific rejection antigens, as shown by excision of the primary tumours and i.p. or i.m. injection of graded doses of the specific and unrelated tumour cells. I.p. challenge with tumour cells induced a large and relatively long-lasting increase in numbers of peritoneal leucocytes. Macrophage monolayers prepared from such exudates were, in general, non-specifically cytotoxic, though occasional specific cytotoxicity was detected. T lymphocytes isolated from exudates were shown to kill in a specific manner. When immunized mice were challenged with the specific tumour cells to elicit large numbers of peritoneal cytotoxic cells, and with graded doses of the non-cross-reacting tumour cells at the same time or at various times thereafter, growth of the non-related tumours occurred in all cases and only the specific tumour was rejected. Moreover, Winn tests, in which the inflammatory cells were mixed with unrelated tumour cells and implanted i.m., did not delay tumour growth. The relevance of these findings to the role of macrophages and lymphocytes in syngeneic tumour rejection is discussed.

Animals

The definition of transcription units for mRNA.

The detailed analysis of TUs with purified Ad2 DNA and the analysis of TU size for the bulk HeLa cell hnRNA compared to the size of mRNA of infected and uninfected cells supports the conclusion that mRNA in mammalian cells is generally derived by the processing of primary transcripts. In the context of this volume, these results indicate that the RNA transcription products of chromatin which are related to mRNA are longer than the mRNA itself. Proper functioning of chromatin in vitro must eventually take these results into account.

Adenoviruses, Human

Effect of dopamine on hemodynamics and myocardial metabolism in shock following acute myocardial infarction in man.

Eight patients in shock associated with acute myocardial infarctions were treated with dopamine. We titrated the dopamine dose to increase mean arterial pressure to 65-70 mm Hg and urine output to greater than 40 ml/hr. Increase of heart rate to 120-125 beats/min and occurrence of potentially dangerous arrhythmias were limiting end-points. Dopamine administration averaged 17.2 microgram/kg/min. Heart rate increased from 95 to 118 beats/min (P less than 0.001), and mean arterial pressure rose from 60 to 65 mm Hg (P less than 0.05). Dopamine increased myocardial contractility as indicated by increase in cardiac index and systolic ejection rate, with only moderate decrease in systemic vascular resistance. Pulmonary wedge pressure and right atrial pressure decreased from 23 to 18 mm Hg (P less than 0.05) and from 10 to 8 mm Hg (P less than 0.001) respectively. Improvement in hemodynamic status by dopamine was associated with deterioration of myocardial metabolism. Myocardial oxygen extraction ratios and arterial-coronary sinus oxygen differences increased from 73 to 76% (P less than 0.05) and from 13.02 to 14.19 ml/100 ml (P less than 0.02) respectively. Myocardial lactate production increased from -8 to -15% (P = 0.05). We conclude that dopamine improved cardiac performance at the expense of myocardial oxygenation and that dopamine is potentially harmful to acutely ischemic myocardium.

Acute Disease

Selective IgA deficiency and Pi ZZ-antitrypsin deficiency. Association with recurrent sinopulmonary infections, emphysema, and bronchiectasis.

We describe a patient in whom selective IgA deficiency and homozygous alpha1-antitrypsin deficiency were discovered. Clinically, the patient suffered from chronic sinopulmonary infections, destructive emphysema, and bronchiectasis. The interrelation of IgA and alpha1-antitrypsin was studied. Twenty-three alpha1-antitrypsin-deficient sera were screened for IgA deficiency. None of these sera were deficient in IgA. Fifteen IgA-deficient sera were screened for alpha1-antitrypsin deficiency. In this group, three patients were found to have variant alpha1-antitrypsin phenotypes. Respiratory infections were a prominent complaint in all three of these patients, with bronchiectasis in two patients. We believe that the combination of IgA and alpha1-antitrypsin deficiencies should be considered in the evaluation of any patient with idiopathic bronchiectasis.

Bronchiectasis

Combined modality therapy for stage IIIMO non-oat cell bronchogenic carcinoma.

Thirty-nine patients with stage IIIMO non-cell bronchogenic carcinoma (NOBC) were treated with combined modality therapy: radiation therapy and chemotherapy with cyclophosphamide, adriamycin, methotrexate, and procarbazine. The median survival for all patients treated was 9.6 months compared to 6.4 months for historical controls (P = 0.015). Patients who responded to the treatment program had a significantly longer survival (median, 15.2 months) compared to nonresponders and historical controls (P less than 0.005). It is concluded that combined modality therapy is moderately effective therapy in stage IIIMO NOBC.

Carcinoma, Bronchogenic

Haemoperfusion with R-004 Amberlite resin for treating acute poisoning.

Eleven patients who had taken overdoses of barbiturates, glutethimide, tricyclic antidepressants, and chloroquine were treated by resin haemoperfusion using an R-004 haemoperfusion cartridge containing XAD-4 resin. All but one patient showed rapid clinical recovery and the drugs were cleared rapidly from the plasma. There were few complications. Resin haemoperfusion is more effective than dialysis and other perfusion methods, especially in poisoning with tricyclic antidepressants. Although haemoperfusion is expensive, it greatly reduces the length of the patient's stay in an intensive care unit and hence is cost-effective.

Acute Disease

The effect of azathioprine on host cell infiltration and growth of a murine fibrosarcoma.

Azathioprine (AZ) was injected into C57 Black mice before or after IM implantation of the syngeneic fibrosarcoma FS6, and observations were made on tumour growth and on the cellular composition of the fibrosarcomas. When multiple injections were given to the tumour-bearing host the tumours regressed. The percentage of tumour-associated macrophages remained essentially stable as regression occurred whereas the percentage of theta-antigen-positive cells increased. In the case of single IP injections of AZ, changes in the cellular composition of tumours were seen only when AZ was given 1-72 h before implantation but not when it was given after implantation. Compared with controls there was a 2- to 3-week delay in the appearance of large numbers of tumour-associated macrophages. The percentage of theta-antigen-positive cells within the tumours mass was elevated 7 days post AZ treatment but the level declined to control values between days 10 and 13. The significance of the results is discussed in relation to the dependency of the macrophage content of this tumour upon the development of an immune response towards the tumour.

Animals

Further studies on the mechanism of human histamine-induced asthma: the effect of an aerosolized H1 receptor antagonist (diphenhydramine).

This study was designed to better define the mechanism of histamine-induced bronchoconstriction in humans by pharmacologic manipulation of the postulated bronchial histamine receptor sites. Histamine challenges were performed on a heterogeneous group of adult asthmatic subjects. The cumulative units of histamine required for induction of a sustained 20% or greater decrease in FEV1 from baseline were determined. The effect of pretreatment with an aerosolized H1 receptor antagonist, diphenhydramine hydrochloride, was then studied. Analysis of the data showed that the administration of an H1 receptor antagonist prior to histamine challenge significantly blocked the bronchial response to histamine (p less than 0.005). This effect was considered to be due to specific competitive antagonism at the H1 receptor site and suggests the presence of H1 receptors in human bronchial mucosa.

Asthma