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Biomedical subjects

R Ward

Publications and source records attributed to R Ward.

At least 253 records · Page 14Linked to original sources

Rheumatic disease in the Nuu-Chah-Nulth native Indians of the Pacific Northwest.

The Nuu-Chah-Nulth are a tribe of 2,300 Pacific Northwest native Indians. A retrospective study has identified 157 requiring referral to rheumatologists over 15 years. Rheumatoid arthritis (RA) was found in 23, systemic lupus erythematosus (SLE) in 8, sacroiliitis 5, and Reiter's syndrome 1. Overlap syndromes with combinations of RA, SLE, scleroderma and polymyositis were seen in 9. Other rheumatic disorders included osteoarthritis 10, soft tissue rheumatism 14, and musculoskeletal complaints of known etiology (trauma, infection, neoplasm) 12. The remaining 75 patients suffered from periodic weather dependent joint swelling (52) or polyarthralgia (23) which were sometimes accompanied by features of systemic connective tissue disease. These findings are compared with rheumatic disease in other North American Indians.

Antibodies, Antinuclear↗

The relationship between callosal variation and lateralization in mice is genotype-dependent.

The relation between morphological variation of the corpus callosum and variation in the degree of paw preference was investigated in 129/J and BALB/cCF mice. A positive relationship explaining 24% of the variance of paw preference was found in 129/J mice; no such relationship exists in BALB/cCF mice. It is suggested that, since the genetic dissimilarity between these two inbred strains is comparable in magnitude with the genetic dissimilarity between unrelated human subjects, genetic variation may have been an uncontrolled source of heterogeneity in previous human neuropsychological studies.

Animals↗

The simultaneous presentation of peripheral T-cell lymphoma and hairy cell leukemia.

A patient who presented simultaneously with B hairy cell leukemia (HCL) and peripheral T-cell lymphoma (PTL) is described. The diagnoses of the two neoplasms were made by standard morphologic and cytochemical study and confirmed immunologically. There was no evidence of overlap in markers to suggest that they arose from a single clone of malignant cells. It is suggested that the simultaneous occurrence of the two neoplasms in the same patient reflects an underlying predisposition to the development of neoplasia in HCL.

Antibodies, Monoclonal↗

Enrichment of Na+-Ca2+ exchange in cardiac sarcolemmal vesicles by alkaline extraction.

Exposure of canine cardiac sarcolemmal vesicles to alkaline media (greater than or equal to pH 12) results in the extraction of 33% of the protein. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis shows that specific proteins are being solubilized. Most of the phospholipid and sialic acid remains with the pellet after centrifugation. Electron microscopy reveals that alkaline treatment does not cause gross morphological damage to the vesicles, although freeze-fracture demonstrates some aggregation of intramembrane particles. The data indicate that high pH probably removes peripheral proteins and leaves the integral proteins in place. We find complete recovery of Na+-Ca2+ exchange activity in alkaline-extracted membranes after solubilization and reconstitution. These vesicles contain only 50% of the protein of vesicles reconstituted from control sarcolemma. Thus, the specific activity of Na+-Ca2+ exchange is doubled. Alkaline extraction is a useful and reproducible procedure for enrichment of the Na+-Ca2+ exchange protein. (Na+ + K+)-ATPase is completely inactivated by exposure to pH 12 medium though immunodetection shows that the (Na+ + K+)-ATPase proteins are not extracted. We detect both alpha and alpha + forms of (Na+ + K+)-ATPase and deduce that the Na+ pump proteins do not comprise a major fraction of sarcolemmal protein.

Animals↗

Modulation of Na+-Ca2+ exchange and Ca2+ permeability in cardiac sarcolemmal vesicles by doxylstearic acids.

We examine the effects of 5-, 12- and 16-doxylstearic acids on the Na+-Ca2+ exchange and passive Ca2+ permeability of cardiac sarcolemmal vesicles. Stearic acid is a weak stimulator of Na+-Ca2+ exchange. A doxyl moiety potentiates stimulation with the order of increasing potency being 5-, 12- and then 16-doxylstearic acid. Stearic acid has little effect on vesicle Ca2+ permeability but again the doxylstearates are more effective. The sequence of potency is reversed, however, from that for increasing Na+-Ca2+ exchange. 5-Doxylstearic acid most markedly exchanges passive Ca2+ flux followed by the 12-, and then 16-doxylstearic acids. Methyl esters of the doxylstearates have no effect on either Na+-Ca2+ exchange or Ca2+ permeability. We model the results as follows. For a fatty acid to stimulate Na+-Ca2+ exchange activity, an anionic charge is required to interact with the exchanger protein at the membrane surface. Stimulation is potentiated by a perturbation (such as provided by a doxyl group) within the lipid bilayer. The perturbation is most effective at a location towards the center of the bilayer. To increase passive Ca2+ permeability an anionic charge is again essential. Disorder within the bilayer is also important, but now the most important site is near the membrane surface. Results of experiments with linolenic and gamma-linolenic acid and previous studies with other fatty acids also support this model.

Animals↗

A neuropsychological study of active amateur boxers.

Neuropsychological examinations were carried out on 29 amateur boxers and 19 controls matched for age, ethnicity, and education. There was no evidence of significantly impaired performance in the boxers. Within the boxing group, a variety of features of boxing history were examined as possible predictors of cognitive performance (such as number of knockouts, duration of boxing). No feature was a significant predictor of lower cognitive performance.

Adolescent↗

Treatment of NZB/NZW mice with total lymphoid irradiation: long-lasting suppression of disease without generalized immune suppression.

We used total lymphoid irradiation (TLI; total dose = 3400 rad) to treat the lupus-like renal disease of 6-mo-old female NZB/NZW mice. Similar to our past studies, this treatment resulted in a marked prolongation of survival, decrease in proteinuria, and decrease in serum anti-DNA antibodies compared with untreated littermate controls. Although there was no evidence of disease recurrence in TLI-treated mice until after 12 mo of age, the in vitro proliferative response to phytohemagglutinin by NZB/NZW spleen cells recovered within 6 wk such that responses were greater than control NZB/NZW animals. A similar recovery and overshoot after TLI were evident in the primary antibody response to the T cell-dependent antigen sheep red blood cells (SRBC). Both the total and IgG anti-SRBC antibody responses after TLI were greater than those of untreated NZB/NZW controls, and were comparable with those of untreated non-autoimmune mice. Despite this increased response to mitogens and antigens after TLI, we noted a decrease in spontaneous splenic IgG-secreting cells and a decrease in IgG but not IgM antinuclear antibody production. Nonspecific suppressor cells of the mixed leukocyte response were detectable in the spleens of NZB/NZW mice early after TLI. However, the disappearance of suppressor cells was not associated with recrudescence of disease activity. Furthermore, transfer of large numbers of spleen cells from TLI-treated NZB/NZW mice did not result in disease suppression in untreated age-matched recipients. In summary, treatment of NZB/NZW mice with TLI results in a prolonged remission in autoimmune disease, which is achieved in the absence of generalized immunosuppression.

Animals↗

Role for sulfur-containing groups in the Na+-Ca2+ exchange of cardiac sarcolemmal vesicles.

Different amino acid residues in cardiac sarcolemmal vesicles were modified by incubation with various chemical reagents. The effects of these modifications on sarcolemmal Na+-Ca2+ exchange were examined. Dithiothreitol, an agent that maintains sulfur-containing residues in a reduced state, caused a time- and concentration-dependent decrease in Na+-Ca2+ exchange. The treatment with dithiothreitol resulted in a decrease in Vmax values but did not alter the Km for Ca2+ for the Na2+-Ca2+ exchange reaction. If Na+ replaced K+ as the ion present during the modification of sarcolemmal membranes with dithiothreitol, there was substantially less of an inhibitor effect on Na+-Ca2+ exchange. Similar results were obtained with reduced glutathione, a reagent that also maintains sulfur-containing residues in a reduced state. Two sulfhydryl modifying reagents, methylmethanethiosulfonate and N'-ethylmaleimide, were capable of altering Na+-Ca2+ exchange, and the type of ion present during modification significantly affected the extent of this alteration. Almost all of the chemical reagents investigated that modified other amino acid resides (carboxyl, lysyl, histidyl, tyrosyl, tryptophanyl, arginyl and hydroxyl) had the capacity to alter Na+-Ca2+ exchange after preincubation with the sarcolemmal membrane vesicles. However, the sulfur residue-modifying reagents were the only compounds to exhibit significant differences in their action on Na+-Ca2+ exchange, depending on whether Na+ or K+ was present in the preincubation modification medium. The tryptophan modifier, N-bromosuccinimide, was the sole reagent that elicited a substantial increase in membrane permeability. The evidence is consistent with the hypothesis that sulfur-containing residues interact with a Na+-binding site for Na+-Ca2+ exchange in cardiac sarcolemmal vesicles.

Animals↗

Ca2+ transport capacity of sarcolemmal Na+-Ca2+ exchange. Extrapolation of vesicle data to in vivo conditions.

Na+-Ca2+ exchange activity is high in cardiac sarcolemmal vesicles suggesting an important physiologic role. Vesicular Na+-Ca2+ exchange, however, is usually measured under conditions which are far from physiologic. Using sarcolemmal vesicles, we have estimated the possible significance of both Ca2+ influx and efflux mediated by Na+-Ca2+ exchange under approximate in vivo ionic conditions. In this situation, Na+-Ca2+ exchange activity is far from maximal with intracellular Mg2+ causing significant inhibition. The capacity of the Na+-Ca2+ exchange system to extrude intracellular Ca2+ (at [Ca2+] = 6.0 microM) is about 1.2 mumol Ca2+/kg wet weight/s and approximately equals the capacity of the sarcolemmal ATP-dependent Ca2+ pump. The capacity of the sarcoplasmic reticular Ca2+ pump to remove cytoplasmic Ca2+ is much larger. Significant Ca2+ influx through the exchanger is unlikely to occur in normal mammalian myocardium and would require reduced extracellular Na+ or elevated intracellular Na+.

Adenosine Triphosphate↗

Mucus degradation by pepsin: comparison of mucolytic activity of human pepsin 1 and pepsin 3: implications in peptic ulceration.

The ability to digest mucus, mucolytic activity of isolated pepsins and samples of human gastric juice has been assayed by measuring the fall in viscosity when incubated with purified pig gastric mucus glycoprotein. Pure human pepsin 1, the peptic ulcer associated pepsin, digested gastric mucus glycoprotein at a faster rate than did pure human pepsin 3 (the principal human pepsin), or the equivalent pig pepsin (pepsin A). At pH 2.0 pepsin 1 had twice the mucolytic activity of pepsin 3. Above pH 3.8 this difference became more marked and whereas pepsin 1 caused substantial mucolysis up to and including pH 5.1, pepsin 3 had minimal activity. At pH 4.0 pepsin 1 had six times the mucolytic activity of pepsin 3. Gastric juices from patients with duodenal ulcer each exhibited substantial mucolytic activity between pH 2 to 5, similar to that of pepsin 1. In contrast, gastric juice from non-symptomatic volunteers exhibited little mucolytic activity above pH 4. Analysis of the mucus glycoprotein by gel filtration showed that an increase in lower molecular weight, pepsin degraded, glycoprotein was associated with the fall in mucus viscosity for all enzyme preparations. These results showed that pepsin 1 can digest the mucus more effectively than pepsin 3 and at higher pH values. The raised concentrations of pepsin 1 in the juice of peptic ulcer patients may thus promote the ulcerative process by increased erosion of the mucus barrier under conditions likely to pertain in the duodenal bulb as well as the stomach.

Chromatography, Gel↗

Chemical analysis of compounds extracted from the tergal "spots" of Lutzomyia longipalpis from Brazil.

The chemical composition of the compounds contained in the tergal spots of Lutzomyia longipalpis was investigated. Four populations of L. longipalpis were examined, originating from: Sobral, Ceará, Brazil (one spot and two spot populations), Santarém, Pará, Brazil (one spot) and Marajó Island, Pará, Brazil (one spot). The tergal spots were dissected out, extracted in hexane and analysed on a gas chromatograph/mass spectrometer. Two compounds were found, identical to compounds found in earlier studies, but there was no correlation between number of tergal spots and type of compound present. It was suggested that the number of tergal spots could not be used as a marker for reproductively isolated populations, and that analysis of the compound present within the spots might be necessary to characterize potentially good vector populations.

Animals↗

Effects of fatty acids on Na+-Ca2+ exchange and Ca2+ permeability of cardiac sarcolemmal vesicles.

We have previously reported that anionic phospholipids (Philipson, K.D., and Nishimoto, A.Y. (1984) J. Biol. Chem. 259, 16-19) and other anionic amphiphiles (Philipson, K.D. (1984) J. Biol. Chem. 259, 13999-14002) stimulate Na+-Ca2+ exchange in cardiac sarcolemmal vesicles. To further these studies, we have now investigated the effects of a variety of fatty acids on both Na+-Ca2+ exchange and passive Ca2+ permeability. Na+-Ca2+ exchange was stimulated by fatty acids by up to 150%. Unsaturated fatty acids were more potent than saturated fatty acids, and the stimulation was primarily due to a decrease in the apparent KM (Ca2+). There was a positive correlation between the ability of a fatty acid to stimulate Na+-Ca2+ exchange and to increase passive Ca2+ permeability. The methyl esters of fatty acids had no effects on either exchange or permeability indicating the importance of anionic charge. We conclude that the combination of local lipid disorder and anionic charge regulate Na+-Ca2+ exchange. Perturbations of the bilayer hydrophobic region and increased negative surface charge are both required for fatty acids to increase passive Ca2+ flux. Na+-Ca2+ exchange is stimulated when the ratio of membrane free fatty acid to phospholipid is about 5%. This level of fatty acid is achieved during 1 h of myocardial ischemia (Chien, K. R., Han, A., Sen, A., Buja, L. M., and Willerson, J. T. (1984) Circ. Res. 54, 313-322), indicating that ischemia could induce altered sarcolemmal Ca2+ transport due to fatty acid accumulation.

Animals↗

Brain size and shape in strongly and weakly lateralized mice.

Mice from two selected lines differing markedly in their degree of lateralization, and from a random-bred control line, were studied. The brains of strongly lateralized mice were found to be heavier, and those of weakly lateralized mice to be lighter, than those of control mice of equivalent body weight; the degree of cerebral asymmetry was found to be least in weakly lateralized mice; and the corpora callosa of both selected lines were smaller than those of control mice. These findings are tentatively interpreted in terms of the effects of different behavioral strategies on the development of the central nervous system.

Agenesis of Corpus Callosum↗