Biomedical subjects

N Alexander

Publications and source records attributed to N Alexander.

117 records · Page 7Linked to original sources

PubMedDate not supplied

Observer variation in quantification of immunocytochemistry by image analysis.

This paper reports the findings of a study designed to examine observer variation as a source of inaccuracy inherent in the use of computer-assisted image analysis to measure areas of stained tissue. The rat pituitary immunostained for prolactin and galanin was used as an example to estimate patterns of immunoreactivity exhibited by different cell types. Six observers, with differing experience, selected grey level threshold values on 40 fields of images of stained tissue making three repeats of each field. The 40 fields consisted of 20 serial pairs of colocalized fields, one immunostained for prolactin, the other for galanin. The 20 pairs consisted of four pairs from each of five animals. Analysis of observer variation in the selection of threshold values showed large differences in the within- and between-observer variation. Analysis of the components of variance in the estimation of the ratios of stained tissues showed that the major source of variation was the within-observer component. An additional experiment using two observers, where half of the images were compared to the original microscope images before setting threshold levels, showed that the opportunity to make a comparison did not reduce observer variation. It is suggested that any study which uses semi-automatic methods to segment regions of a digital image can benefit from an analysis of this kind so that the sources of variation can be determined to enable maximum discriminating power in future studies.

Animals↗

PubMedDate not supplied

Area effects of bednet use in a malaria-endemic area in Papua New Guinea.

Relationships between area coverage with insecticide-free bednets and prevalence of Plasmodium falciparum were investigated in 7 community-based surveys over a 33-month period in 1990-93 in 6 villages in the Wosera area of Papua New Guinea. Spatial patterns in circumsporozoite rates for P. falciparum, P. vivax isomorphs K210 and K247, and P. malariae, and the proportions of mosquito blood meals positive for specific human, goat, cat, dog and pig antigens were determined using ELISAs. P. falciparum prevalence in humans was better explained by bednet coverage in the immediate vicinity than by personal protection alone. Circumsporozoite rates for both P. falciparum and P. vivax were also inversely related to coverage with bednets. There was some increase in zoophagy in areas with high coverage, but relatively little effect on the human blood index or on overall mosquito densities. In this setting, protracted use of untreated bednets apparently reduces sporozoite rates, and the associated effects on prevalence are greater than can be accounted for by personal protection. Even at high bednet coverage most anophelines feed on human hosts, so the decreased sporozoite rates are likely to be largely due to reduction of mosquito survival. This finding highlights the importance of local vector ecology for outcomes of bednet programmes and suggests that area effects of untreated bednets should be reassessed in other settings.

Adolescent↗

PubMedDate not supplied

The late biting habit of parous Anopheles mosquitoes and pre-bedtime exposure of humans to infective female mosquitoes.

Using the all-night landing catch method (18:00-06:00) we showed, for Anopheles gambiae in Sierra Leone and A. punctulatus in Papua New Guinea, that parous females have a tendency to bite later than nulliparous ones. The biting habit of sporozoite-infected A. punctulatus was also investigated. The sporozoite rates for Plasmodium falciparum and P. vivax were 1.8 and 1.4% respectively, but only one (1.3%) of 76 females infected with P. falciparum was caught between 18:00 and 21:00. A significantly higher proportion (11.6%) of mosquitoes infected with P. vivax was caught in the same period. The late biting habit of mosquitoes infected with P. falciparum is discussed in relation to the differential biting habits of parous and nulliparous females. We conclude with a hypothesis that, in areas where Anopheles mosquitoes have a late-biting cycle and low parous rate, exposure to mosquitoes infected with P. falciparum during the pre-bedtime period (18:00-22:00) is very low. This hypothesis could explain why insecticide-treated bed nets protect children better in areas of seasonal transmission, where nulliparous females tend to predominate, than in areas of perennial transmission, where parous females are usually more numerous. The same hypothesis is compatible with the finding in Papua New Guinea that insecticide-impregnated bed nets are more protective against P. falciparum than against P. vivax malaria.

Animals↗

PubMedDate not supplied

Hemizona assay and its impact on the identification and treatment of human sperm dysfunctions.

The HZA, a functional test for human gamete interaction, has become a useful and valuable experimental tool for physiological and cellular analysis of the early events leading to fertilization. The analysis of the conventional semen parameters with emphasis on sperm morphology (as judged by strict criteria) and motion characteristics (evaluated by computer assisted analysis) constitutes the first obligatory step for a critical evaluation of male-factor patients. Patients in whom fertilization disorders are suspected should be evaluated through bioassays of sperm function of established accuracy. The HZA, a bioassay of sperm-zona binding capacity is here proven to be highly predictive of IVF outcome. Ultimately, our increasing knowledge of sperm biology and dysfunction will provide a basis for a better diagnosis (membrane receptor defects and metabolic/biochemical abnormalities?) as well as better therapeutic interventions in patients with sperm disorders. It seems likely that the HZA may be eventually replaced by a standardized test kit in which recombinant human DNA-derived zona receptors mimic the natural function of the hemizonae currently used. This ZP3 reagent may also be a useful antigen for contraceptive development. The HZA therefore constitutes a useful adjuvant in the armentarium for the diagnosis and therapy of male-factor patients.

Contraception↗

PubMedDate not supplied

Altered in vitro uptake of norepinephrine by cardiovascular tissues of spontaneously hypertensive rats. Part 1. Mesenteric artery.

The incorporation of tritiated norepinephrine (NE) by mesenteric arteries from spontaneously hypertensive rats (SHR) of the Okamoto strain and from age-matched Wistar Kyoto (WKY) controls was studied. The arteries were incubated with tritiated NE, and fractions were isolated by differential and sucrose density gradient centrifugations. The amount of radioactivity present in certain subfractions (P3 pellet) of the SHR arteries was significantly higher than that of WKY arteries. When the P3 subfraction was lysed and subjected to sucrose density gradient centrifugation, the tritiated NE was found to ba associated with the 0.4-0.5 M interface. Electron micrographs of the P3 subfractions revealed a variety of vesicular structures which might represent storage sites for the tritiated NE. Although a number of factors could account for the finding of enhanced incorporation into mesenteric artery subfractions of hypertensive rats, the finding is compatible with the work of others who found increased ATPase activity in mesenteric arteries of SHRs, since ATPase is known to activate vesicular NE uptake.

Animals↗

PubMedDate not supplied

Altered in vitro uptake of norepinephrine by cardiovascular tissues of spontaneously hypertensive rats. Part 2. Portal-mesenteric veins and atria.

Norepinephrine (NE) incorporation by portal-mesenteric veins (P-M) veins) and atria of spontaneously hypertensive rats (SHR) were compared with that of age-matched Wistar Kyoto controls (WKY). Tissues were incubated in the presence of tritiated norepinephrine (3H-NE), and fractions were isolated by means by differential and sucrose density gradient centrifugation. The peak of radioactivity was located in the 0.4-0.5 M sucrose region that contained vesicular materials, as shown by electron micrography. NE incorporation (picomoles/mg tissue) into the P3 subfraction of SHR atria and P-M veins was reduced; in atria, the reduction was statistically significant. These results contrasted with the enhanced 3H-NE incorporation by SHR mesenteric artery, and point out regional differences in this process.

Animals↗

PubMedDate not supplied

Sympathetic system function and vascular reactivity in hypercalcemic patients.

To elucidate the pathophysiology of elevated blood pressure in hypercalcemic patients, we studied the plasma concentration of catecholamines and their major metabolites (as an index of sympathetic function) and the blood pressure response to norepinephrine infusion (vascular reactivity) in patients with primary hyperparathyroidism, in patients with primary hypertension, and in normal controls. In addition, we evaluated the hemodynamic response to calcium infusion in normotensive and hypertensive subjects. Plasma levels of both norepinephrine and epinephrine and the metabolites normetanephrine and dihydroxyphenyl-glycol were significantly higher in the hypercalcemic group than in the other two groups. Norepinephrine infusion increased blood pressure by 8.5 +/- 1.4 mm Hg in the control group, by 19 +/- 2 mm Hg in the hypercalcemic group and by 29 +/- 3 mm Hg in the primary hypertensive group. Infusion of calcium produced a significant rise in both systolic and diastolic blood pressures and in peripheral resistance in the hypertensives, whereas in the normotensive group only systolic blood pressure increased, associated with a rise in cardiac output. We conclude that the observed increased activity of the sympathetic nervous system in hypercalcemia could account for the elevation in blood pressure and the enhanced vascular reactivity could explain the hypertension in some patients with primary hyperparathyroidism.

Adult↗

PubMedDate not supplied

Enhanced NE uptake by isolated hypothalamic storage vesicles of hypertensive rats.

The in vitro uptake of 3H-NE by storage vesicles from the hypothalamus of age-matched spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats has been studied using a new reliable procedure for the isolation of biochemically active storage vesicles. In each of 13 paired studies, done in triplicate, storage vesicles of SHR took up more 3H-NE than those of WKY. (The mean difference was 37% more uptake by SHR.) Electron-microscopic examination of normotensive samples showed a concentration of intact synaptic vesicles; whereas SHR subfractions were composed of fragmented membranes that resembled swollen, distorted vesicles. These findings in the brain tissues of SHR parallel our previous results found in SHR peripheral tissues. Taken together, we interpret the results to indicate that the membranes of synaptic vesicles of SHR are altered structurally and biochemically.

Animals↗

PubMedDate not supplied

Sympathetic activity and cardiac adrenergic receptors in one-kidney, one clip hypertension in rats.

The activity of the sympathetic nervous system, as measured by levels of plasma and cardiac catecholamines and catecholamine metabolites and the function of cardiac alpha- and beta-adrenergic receptors, was evaluated at 3 days and 4 weeks after induction of one-kidney, one clip hypertension (1K1C) in the rat. At 3 days, the plasma level of norepinephrine (NE) was lower in the 1K1C group than the control group (p less than 0.01), whereas epinephrine (E) and the metabolites dihydroxymandelic acid (DOMA), dihydroxyphenylglycol (DOPEG), and normetanephrine (NMN) were similar in both groups. In addition, cardiac content of catecholamines, their metabolites, and adrenergic receptors were similar in both groups. At 4 weeks, plasma levels of NE and DOPEG were lower (p less than 0.01), whereas levels of DOMA and NMN were higher (p less than 0.02 and p less than 0.001, respectively) in the 1K1C group than the control group. Cardiac content of NE (p less than 0.01), and DOPEG (p less than 0.05) was significantly lower, whereas DOMA and NMN were significantly higher (p less than 0.01) in the 1K1C group as compared to controls. In addition, cardiac density of both alpha- and beta-adrenergic receptors was reduced in the 1K1C group, whereas receptor affinities were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗