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Biomedical subjects

J Stewart

Publications and source records attributed to J Stewart.

At least 487 records · Page 27Linked to original sources

Peripheral neuropathy with IgM kappa monoclonal immunoglobulin directed against myelin-associated glycoprotein.

Three patients with a monoclonal IgM kappa paraproteinemia had a slowly progressive segmental demyelinating peripheral neuropathy. Sural nerve biopsies showed predominantly large fiber loss, with widening of the intraperiod line of myelin associated with active demyelination. Immunoblot analysis showed reactivity of IgM to myelin-associated glycoprotein (MAG) of human myelin. An enzyme-linked immunosorbent assay (ELISA) was developed to provide a simple quantitative technique for detection of antibodies to MAG. Treatment with corticosteroids, immunosuppressive agents, and plasmapheresis produced no significant improvement.

Aged↗

Membrane changes in murine macrophages after in-vivo stimulation and activation.

The expression of various receptors and other surface determinants on resident, glycogen-and Corynebacterium parvum- elicited mouse peritoneal macrophages has been described. Macrophage Fc (IgG2b) receptors and I-A antigens were slightly increased after stimulation and a more marked increase was shown after activation with C. parvum. Complement receptor expression was enhanced after stimulation but was markedly reduced after activation. C. parvum-elicited macrophages, and to a lesser extent glycogen-elicited macrophages, showed a reduction in lectin-like receptors which recognize bacterial cell-wall sugars. Surface mannosyl determinants of the macrophage membrane were apparently increased after activation. The environment thus can be seen to influence the expression of macrophage surface receptors and antigens. These alterations are likely to influence the role of the macrophage in the immune response.

Acid Phosphatase↗

Macrophage binding of Staphylococcus albus is blocked by anti I-region alloantibody.

Cell surface interactions involving carbohydrate may be important in immune recognition. Previous work from this laboratory has demonstrated the presence of 'lectin-like' receptors on mouse peritoneal macrophages that bind bacteria by means of their cell wall sugars. Others have shown that Ia molecules can bind antigen at specific sites which may be involved in presenting antigen to the immune system and recent work has shown that these molecules can carry carbohydrate determinants. It has also been found that human Ia molecules can bind to carbohydrates. As cell surface carbohydrate recognition mechanisms have been implicated in other immune interactions sugar-specific receptors may have a function in self--non-self recognition. We show here that the binding of the bacterium Staphylococcus albus to mouse peritoneal macrophages was inhibited by various conventional and monoclonal antibodies to Ia antigens suggesting that an I-region gene product may be associated with the binding of unopsonized bacteria.

Animals↗

Predictive value of SS-B precipitating antibodies in Sjoögren's syndrome.

As part of a screening programme several patients were identified with antibodies to the nuclear antigen SS-B. Fifteen were examined and 11 found to have Sjögren's syndrome, though this had not been suspected by most of the referring physicians. In contrast, among a group of 17 patients with overt Sjögren's syndrome, most of whom also had rheumatoid arthritis, only one had antibodies to SS-B. Patients presenting with polyarthralgia found to be SS-B positive may be likely to develop Sjögren's syndrome but unlikely to develop rheumatoid arthritis. The detection of SS-B antibodies may antedate clinical evidence of Sjögren's syndrome by months or even years. These results emphasise the clinical heterogeneity of Sjögren's syndrome.

Adult↗

Q fever in maritime Canada.

Only nine cases of Q fever were recorded in Canada in the 20 years prior to 1978. In the 18 months from August 1979 to January 1981 the disease was diagnosed serologically in six patients from the Maritime provinces. All were epidemiologically unrelated and none had been exposed to animals. Five had pneumonia and one had chronic Q fever with probable prosthetic valve endocarditis. Three of the five pneumonia patients presented with signs and symptoms of an acute lower respiratory tract infection and were indistinguishable clinically from other patients with atypical pneumonias. The other two with pneumonia presented with nonresolving pulmonary infiltrates and complained of decreased energy. Four of the five pneumonia patients responded well to treatment with erythromycin; the fifth required two courses of tetracycline. The patient with chronic Q fever had a large amount of cryoglobulins in his serum and evidence of immune complex disease. These cases indicate that Q fever should be considered as a possible cause of atypical pneumonia in Canada.

Adult↗

Estrogen and progesterone receptors: correlation of response rates, site and timing of receptor analysis.

156 patients with advanced breast cancer of known estrogen receptor (ER) and progesterone receptor (PgR) status treated by endocrine therapy were studied. Regarding values for ER and PgR greater than or equal to 5 fmole/mg cytosol protein as positive, patients were divided into 4 phenotypic subgroups: ER+PgR+ (43%), ER+PgR- (26%), ER-PgR+ (8%), and ER-PgR- (23%). In patients with tumor phenotype ER+PgR+, responses were seen in 20/30 (67%) assessable initial treatments when receptor assays were performed on tumor recurrence or on primary tumor immediately before endocrine therapy, and in only 11/32 (34%) assessable initial treatments when receptor analysis was performed on primary tumor and there was intervening local therapy before endocrine therapy was started for tumor recurrence (P less than 0.05). Responses to first endocrine therapy for each tumor phenotype were ER+PgR+ 50%, ER+PgR- 27%, ER-PgR+ 27%, and ER-PgR- 6%. Four of 16 (25%) patients with ER+PgR+ tumors responded to subsequent secondary endocrine therapy, but such responses were not observed in 20 patients with other tumor phenotypes. Duration of response was similar for each phenotype, but patients with ER-PgR- tumors had a significantly shorter survival from time of initial endocrine treatment than patients of any other phenotype. These results suggest that repeat steroid receptor assays on accessible tumor immediately before endocrine therapy may result in improved predictability.

Aged↗

Radionuclide evaluation of postextrasystolic potentiation of left ventricular function induced by atrial and ventricular stimulation.

Postextrasystolic potentiation of left ventricular function induced by ventricular and atrial stimulation was compared in 10 patients using radionuclide ventriculography. After insertion of pacing wires, a preliminary radionuclide ventriculogram was obtained and then ventricular and atrial trigeminy was induced in random order, each with identical R-R coupling intervals, each for 6 to 10 minutes. During the stimulation studies, radionuclide data were acquired in electrocardiographic gated list mode format. Left ventricular ejection fraction and relative end-diastolic and end-systolic volume changes were measured for each reformatted composite sinus, atrial and ventricular premature beat and potentiated beat. The volume changes were normalized to the count-based values obtained for the sinus beat of the appropriate study. Postextrasystolic potentiation induced by either ventricular or atrial stimulation was characterized by similar significant increases in left ventricular ejection fraction (mean +/- standard deviation 7 +/- 3 percent, p less than 0.01 versus 7 +/- 5 percent, p less than 0.01; difference not significant [NS]) and decreases in relative end-systolic volume (-12 +/- 12 percent, p less than 0.01 versus -12 +/- 8 percent, p less than 0.01; NS) but little change in relative end-diastolic volume (+5 +/- 10 percent, NS versus +4 +/- 7 percent, NS; NS). This was despite a longer compensatory pause (1,120 +/- 220 versus 1,050 +/- 190 ms, p less than 0.01) after the ventricular premature beat. It is concluded that there is no difference in the postextrasystolic potentiation induced by atrial or ventricular premature stimulation.

Adult↗

Effects of estradiol benzoate on the pattern of eating and ethanol consumption.

The effects of daily injections of 5 microgram estradiol benzoate (EB) on the patterns of food and ethanol consumption were studied in ovarectomized rats given free access to food, a 10% ethanol solution, and water. EB led to an immediate, but transient, suppression of both food and ethanol intake. The time course and magnitude of these effects were virtually identical. While the decrease in total food intake was achieved by a permanent decrease in the duration of eating bouts, the decline in total ethanol consumption apparently resulted from decreased rates of licking within bouts. Gradual increases in the frequency of eating and ethanol-drinking bouts allowed total food and ethanol intake to return to baseline within three weeks of the first injection. Total water intake rose three-fold during EB administration and this was due to increases in both the duration and frequency of drinking bouts. The similarity in effects induced by EB on the patterns of food and ethanol intake were discussed in terms of ethanol's caloric property.

Alcohol Drinking↗

Mutagenicity of oil-shale ash.

3 oil-shale ash samples were extracted with solvents and analyzed for mutagenicity with a number of tests systems. In Salmonella typhimurium, the ash extracts were highly mutagenic with the Ames his reversion and the ara-resistant systems. Mutation induction by the ash in Salmonella was independent of metabolic activation and was of the frameshift type. These ash extracts showed a substantial killing effect, but failed to induced ad-3 reversion in Neurospora crassa, gene conversion and mitotic crossing-over in Saccharomyces cerevisiae and TGr mutation in cultured CHO cells.

Animals↗

Phagocyte recognition by lectin receptors.

A "lectin-like" receptor for bacterial cell wall sugars, originally described in the membrane of mouse peritoneal macrophages, which facilitates binding of various bacteria to the macrophage surface, has now been shown to be present on most phagocytes from a variety of species. The role of such a receptor in the inflammatory response has been investigated by examining changes in its expression in response to chemoattractants. The chemoattractants, whilst enhancing or not altering expression of C3 and Fc receptors, respectively, appeared to decrease lectin receptor expression. The possibility of a relationship between I-region gene products of the major histocompatibility complex (MHC) and the bacterial binding lectin receptor was investigated. It was found that various conventional and monoclonal antibodies directed against I-region determinants inhibited binding of bacteria to mouse peritoneal macrophages. These findings suggest the need to examine the possibility that, in addition to phagocytosis and elimination of bacteria, the lectin receptor may also be involved in antigen presentation and macrophage-T-lymphocyte cooperative events leading to an immune response.

Animals↗

Effects of estradiol benzoate and MER-25 on ethanol consumption in the ovariectomized rat.

Daily injections of estradiol benzoate (EB) administered to ovariectomized rats given continuous access to a 10% ethanol solution, to water, and to laboratory chow led to decreases in ethanol consumption. The suppression was transient; ethanol consumption returned to the level of oil-treated control animals after 14 days despite continued hormone administration. This pattern of change in ethanol consumption closely resembled previously reported effects of EB on food intake. It is proposed that a common mechanism was responsible for EB-induced suppression of both food and ethanol intake. Ethamoxytriphetol, MER-25, which antagonizes many estrogen-dependent effects but which mimics the action of EB on food intake, also led to decreases in ethanol consumption that paralleled those reported for food intake. These behavioral effects of EB and MEr-25 were shown not to be due to altered ethanol metabolism or to result from malaise developing out of an interaction between EB and ethanol. It is thus suggested that voluntary consumption of ethanol by the rat is largely due to its caloric content. The relevance of these results for several recent reports of decreased ethanol intake during pregnancy is discussed.

Alcohol Drinking↗

The incidence and epidemiology of retinoblastoma in New Zealand: A 30-year survey.

One hundred cases of retinoblastoma were diagnosed in New Zealand-born children between 1948 and 1977 inclusive. Five patients had an affected parent, and of the remaining sporadic cases 25 had bilateral and 70 unilateral tumours. The frequency of retinoblastoma, 1 in 17,500 births, was similar to that reported for most other countries. There was no evidence of an increase in the incidence of all cases of sporadic retinoblastoma during the 30-year period studied, nor was there any significant fluctuation in their incidence with space and time. There was an excess of bilateral sporadic cases in the southern-most districts of New Zealand, but this was of marginal significance. There was no significance evidence for any environmental influence on the occurrence of retinoblastoma.

Age Factors↗

Cardiac hyper- and hyporesponsiveness after pindolol withdrawal.

Abrupt withdrawal of some beta-adrenergic blockers has resulted in clinical syndromes suggestive of adrenergic hypersensitivity that may be due to an adaptive increase in cardiac beta-receptor responsiveness. it was postulated that the partial agonist activity of pindolol might limit enhanced responsiveness of cardiac beta receptors and prevent or diminish withdrawal manifestations. Pindolol was given to 10 hypertensive patients in doses of 10 mg b.i.d. for at least 4 wk, then abruptly replaced with placebo for 20 days. Cardiac chronotropic responsiveness to isoproterenol was decreased on pindolol and gradually returned to normal over 10 to 20 days with no evidence of enhanced responsiveness. In contrast, both resting and exercise heart rate showed rebound increase in responsiveness between the second to sixth day after pindolol (P less than 0.05). Resting and exercise blood pressures gradually rose to stable values without rebound. Plasma norepinephrine and epinephrine and serum thyroxine and triiodothyronine did not change. These data show that abrupt withdrawal of pindolol after long-term dosing leads to transient cardiac hyperresponsiveness of resting and exercise heart rate at the same time as persistent cardiac hyporesponsiveness to isoproterenol. These opposite effects of pindolol on subsets of cardiac beta-adrenergic chronotropic receptors.

Adult↗

Cardiovascular responses in hyperthyroidism before and during beta-adrenoceptor blockade: evidence against adrenergic hypersensitivity.

The relationship between the sympathetic nervous system and cardiovascular responses has been studied indirectly in ten hyperthyroid patients and age matched euthyroid controls. Nyctohemeral variations in heart rate, and heart rate and blood pressure responses to exercise were measured before and during beta-blockade with slow-release propranolol. Both groups showed a parallel variation in heart rate over 24 h, with an increase in heart rate inthe hyperthyroid group that was the same during the day (27.9 +/- 0.95 beats/min) and during the night (26.7 +/- 0.75 beats/min). Similarly, the increase in resting heart rate (32.7 +/- 4.4 beats/min) in the hyperthyroid group was close to the increase in peak exercise-induced heart rate (25.0 +/- 4.7 beats/min). Adequate beta-blockade was achieved in all subjects as evidenced by a percentage reduction in peak exercise heart rate of 25-45%. Propranolol caused a greater reduction in daytime than night-time heart rate in both groups and blunted the response to exercise. Following beta-blockade, the mean percentage reduction in heart rate and systolic blood pressure during exercise, and heart rate responses over 24 h were similar in hyperthyroid and euthyroid groups. The closest correlation between thyroid hormone levels and heart rate was that of serum total tri-iodothyronine (T3) and nocturnal heart rate during beta-blockade (r=0.92; P less than 0.0001). It is concluded that excess circulating thyroid hormones exert a direct effect on the cardiovascular system additive to the sympathetic nervous system and that there is no evidence of adrenergic hypersensitivity in hyperthyroidism.

Adult↗