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Biomedical subjects

N Johnston

Publications and source records attributed to N Johnston.

At least 37 records · Page 2Linked to original sources
PubMed1982

Relationship between tissue sensitization and IgE antibody production in rats infected with the nematode, Nippostrongylus brasiliensis.

In Nippostrongylus brasiliensis rats, tracheal sensitivity to worm allergens developed prior to intestinal sensitivity and correlated with the early local synthesis of reaginic antibody in the mediastinal (bronchial) lymph nodes. Skin and intestinal sensitivity to worm allergens more nearly correlated with serum reaginic antibody and its synthesis by mesenteric lymph nodes and other tissues. Prostaglandins appeared to modulate intestinal responsiveness to worm allergens. Thus, local reagin synthesis and other microenvironmental factors influence local tissue sensitization and responsiveness to allergens.

Allergens↗
PubMed1981

Thymic mast cell deficiency in avian muscular dystrophy.

In animals with hereditary muscular dystrophy there are thymic abnormalities which may be of etiological significance in the dystrophic process. This study investigated mast cell number and histamine levels in the thymus of normal and dystrophic chickens. For comparison, other lymphoid tissues, namely the spleen and the bursa of Fabricius, and non-lymphoid tissues including the comb and pectoralis major muscle, were similarly studied. Our results show that the thymus of dystrophic adult birds has a deficiency in both mast cell number and histamine content. In the bursa of Fabricius of dystrophic birds a significant elevation in histamine content (microgram/g) was attributed to the abnormally small size of this organ, rather than to an absolute mast cell increase. The deficiency in thymic mast cell number in dystrophic chickens may be significant in the postulated abnormal thymus-muscle interaction of the dystrophic process.

Animals↗
PubMed1980

Gut-associated lymphoid tissue in the chicken. I. Morphology, ontogeny, and some functional characteristics of Peyer's patches.

Lymphoid aggregates with many of the characteristics of mammalian Peyer's patches (PP) were identified in the chicken intestine. These chicken PP could not be seen with the naked eye at the time of hatching, but by 10 days of age, 1 or 2 PP were identified in 50% of the birds. Up to 16 wk of age, the numbers of PP increased to a maximum of 5 per animal and they were widely scattered in the intestine, apart from one that was regularly found about 5 to 10 cm anterior to the ileocecal junction. As the birds aged, the number of PP declined so that in older birds (58 wk) only a single PP was evident near the ileocecal junction. Chicken PP possess: a distinct lymphoepithelium with M cells and strong pinocytotic activity; follicles and a subepithelium zone and central zone similar to those of the cecal tonsil (CT). Studies with in ovo hormonal bursectomy and age-associated involution of PP suggested that the subepithelial zone is a B-dependent area and the central zone a T, or thymus-dependent region. These observations extend our knowledge of gut-associated lymphoid tissue (GALT) in the bird to include the bursa of Fabricius, CT, PP, and aggregates in the urodeum and proctodeum. They raise issues about the roles of chicken PP that may aid our understanding of the functions of mammalian GALT.

Animals↗
PubMed1976

A morphologic study of rabbit bronchial lymphoid aggregates and lymphoepithelium.

Ultrastructural studies of the rabbit bronchial mucosa were performed with scanning and transmission electron microscopy. The former revealed that the bronchus-associated lymphoid aggregates could be distinguished from the surrounding tissue, since they were covered with epithelial cells possessing microvilli but not cilia. These lymphoepithelial cells were irregularly placed and provided crevices of varying dimensions at their junctions with other cells. On transmission electron microscopy, these cells showed scanty cytoplasm, several mitochrondria, few other organelles and only rare phagosomes. Just below the epithelium in the lymphoid aggregates, basophil-like cells were seen regularly and were also found in the lymphoepithelium and adjacent normal bronchila epithelium, here lying between cells above the basement membrane. The possible origin of these cells and their potential relationship to lung defense and hypersensitivity disease are discussed.

Animals↗
PubMedDate not supplied

Erythrocyte membrane ATP binding cassette (ABC) proteins: MRP1 and CFTR as well as CD39 (ecto-apyrase) involved in RBC ATP transport and elevated blood plasma ATP of cystic fibrosis.

In addition to the better-known roles of the erythrocyte in the transport of oxygen and carbon dioxide, the concept that the red blood cell is involved in the transport and release of ATP has been evolving (J. Luthje, Blut 59, 367, 1989; G. R. Bergfeld and T. Forrester, Cardiovasc. Res. 26, 40, 1992; M. L. Ellsworth et al., Am. J. Physiol. 269, H2155, 1995; R. S. Sprague et al., Am. J. Physiol. 275, H1726, 1998). Membrane proteins involved in the release of ATP from erythrocytes now appear to include members of the ATP binding cassette (ABC) family (C. F. Higgins, Annu. Rev. Cell Biol. 8, 67, 1992; C. F. Higgins, Cell 82, 693, 1995). In addition to defining physiologically the presence of ABC proteins in RBCs, accumulating gel electrophoretic evidence suggests that the cystic fibrosis transmembrane conductance regulator (CFTR) and the multidrug resistance-associated protein (MRP1), respectively, constitute significant proteins in the red blood cell membrane. As such, this finding makes the mature erythrocyte compartment a major mammalian repository of these important ABC proteins. Because of its relative structural simplicity and ready accessibility, the erythrocyte offers an ideal system to explore details of the physiological functions of ABC proteins. Moreover, the presence of different ABC proteins in a single membrane implies that interaction among these proteins and with other membrane proteins may be the norm and not the exception in terms of modulation of their functions.

ATP-Binding Cassette Transporters↗
PubMedDate not supplied

Cellular and biophysical evidence for interactions between adenosine triphosphate and P-glycoprotein substrates: functional implications for adenosine triphosphate/drug cotransport in P-glycoprotein overexpressing tumor cells and in P-glycoprotein low-level expressing erythrocytes.

P-glycoprotein is involved with the removal of drugs, most of them cations, from the plasma membrane and cytoplasm. Pgp is also associated with movement of ATP, an anion, from the cytoplasm to the extracellular space. The central question of this study is whether drug and ATP transport associated with the expression of Pgp are in any way coupled. We have measured the stoichiometry of transport coupling between drug and ATP release. The drug and ATP transport that is inhibitable by the sulfonylurea compound, glyburide (P. E. Golstein, A. Boom, J. van Geffel, P. Jacobs, B. Masereel, and R. Beauwens, Pfluger's Arch. 437, 652, 1999), permits determination of the transport coupling ratio, which is close to 1:1. In view of this result, we asked whether ATP interacts directly with Pgp substrates. We show by measuring the movement of Pgp substrates in electric fields that ATP and drug movement are coupled. The results are compatible with the view that substrates for Pgp efflux are driven by the movement of ATP through electrostatic interaction and effective ATP-drug complex formation with net anionic character. This mechanism not only pertains to drug efflux from tumor cells overexpressing Pgp, but also provides a framework for understanding the role of erythrocytes in drug resistance. The erythrocyte consists of a membrane surrounding a millimolar pool of ATP. Mammalian RBCs have no nucleus or DNA drug/toxin targets. From the perspective of drug/ATP complex formation, the RBC serves as an important electrochemical sink for toxins. The presence in the erythrocyte membrane of approximately 100 Pgp copies per RBC provides a mechanism for eventual toxin clearance. The RBC transport of toxins permits their removal from sensitive structures and ultimate clearance from the organism via the liver and/or kidneys.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Phase I trial of 5-fluorouracil by 24-hour infusion weekly.

A novel schedule of 5-fluorouracil administration has been developed for biochemical modulation studies. In combination with the pyrimidine synthesis inhibitor PALA, 5-fluorouracil has been given as a 24-hour infusion, repeated weekly: a dose of 2600 mg/m2 is well tolerated. To identify a suitable dose of 5-fluorouracil as a single agent on this schedule, we treated 26 patients at doses ranging from 2800 to 3400 mg/m2 per week. Two-thirds of the patients had failed previous therapy, and most were symptomatic from their disease. Over half of the patients had metastatic colorectal cancer. The dose-limiting toxicity was diarrhea: Grade 3 or 4 toxicity occurred at every level tested. Twenty-two of the 26 patients required therapy interruption because of toxicity. The severity of this toxicity indicated that escalation of 5-fluorouracil on this schedule beyond the 2600 mg/m2 known to be tolerated in the PALA-containing regimen, would be impractical. Two patients, both with previously untreated colorectal cancer, had partial remissions lasting three and five months respectively. This dose-intense schedule of 5-fluorouracil administration will be explored further in large-scale randomized trials.

Adolescent↗
PubMedDate not supplied

Predicting cardiac complications in patients undergoing non-cardiac surgery.

The authors prospectively studied 455 consecutive patients referred to the general medical consultation service for cardiac risk assessment prior to non-cardiac surgery, in order to validate a previously derived multifactorial index in their clinical setting. They also tested a version of the index that they had modified to reflect factors they believed to be important. For patients undergoing major surgery, the original index performed less well in the validation data set than in the original derivation set (p less than 0.05), but still added predictive information to a statistically significant degree (p less than 0.05). The modified index also added predictive information for patients undergoing both major and minor surgery, demonstrating an area under the Receiver Operating Characteristic curve of 0.75 (95% confidence interval of 0.70 to 0.80). A simple nomogram is presented which will enable conversion of pretest probabilities into posttest probabilities using the likelihood ratios associated with each risk score. It is recommended that clinicians estimate local overall complication rates (pretest probabilities) for the clinically relevant populations in their settings before they apply the predictive properties (likelihood ratios) demonstrated in this study in order to calculate cardiac risks for individual patients (posttest probabilities).

Aged↗