Biomedical subjects
Publications and source records attributed to N White.
Recent innovations in microscopy and digital image processing have greatly enhanced the power of biological imaging. Basic principles of several new methods in light and electron microscopy will be discussed, and examples presented of their application to cell and molecular biology.
Confocal scanning optical microscopy, arguably the most significant in biological light microscopy in this decade, enables one to obtain quantitative non-invasive optical sections through labelled biological specimens, virtually free from out-of-focus blur. A set of these optical sections collected at a series of focal levels through an object constitutes a three-dimensional image which may then be processed digitally for display as a computer reconstruction, a stereo pair or an animation sequence.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The terminal drop hypothesis states that death is preceded by a decrease in cognitive functioning over an approximately five-year period prior to death (Riegel & Riegel, 1972); there is some disagreement as to whether this decrease is pervasive or restricted to specific abilities. The present study assessed the relationship between distance from death and tests of vocabulary, numerical facility, and perceptual speed for 97 subjects who had died within seven years of testing. Only vocabulary scores for those who died at age 70 or less and within two years of testing were affected by terminal drop. An additional analysis comparing the performance of the deceased subjects with a still-living sample matched for age, gender, and education produced nonsignificant results but a trend consistent with the initial analyses. Thus the terminal drop phenomenon may be limited to abilities that typically are relatively unaffected by age, such as vocabulary or other verbal abilities. Furthermore, the effects may be restricted to a time period much closer to death than had been originally proposed.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Multidrug-resistant falciparum malaria is a major health problem along the Thai-Burmese border. From July 1985 until December 1986 a total of 5192 patients with falciparum malaria (1734 males, 3458 females) from this area were given supervised treatment with the combination mefloquine-sulfadoxine-pyrimethamine (MSP). The radical cure rate, assessed 21 days after drug administration, was 98.4% for the first 1975 patients, and 98.8% when assessed at 28 days for the remaining 3217 patients. In 3.8% of cases, parasites were still detected in peripheral blood smears on day 7 after treatment but this had fallen to 0.27% by day 9. Adverse reactions among the first 1975 patients were: vertigo (7.5% of patients), vomiting (5.8%), epigastric pain (0.6%), and transient confusional state (one case). MSP is an effective and well-tolerated drug for the treatment of drug-resistant falciparum malaria; however, delayed parasite clearance may give a false impression of RII resistance.
Explore the source record for details and available documents.
The molecular signals regulating myocardial hypertrophy are unknown. We used a new model system to study this problem. Muscle cells from the neonatal rat ventricle were cultured in serum-free medium. Control cells did not change in size over time and did not show spontaneous contractile activity. Incubation with norepinephrine or epinephrine had two major trophic effects that developed over 1-2 days. The first was stimulation of muscle cell hypertrophy or increase in size. The second was induction of spontaneous contractile activity. The hypertrophic response was mediated through an alpha 1-adrenoceptor. The beating response required both alpha 1- and beta 1-adrenergic receptor stimulation. Alpha 1 stimulation alone produced enlarged cells that did not beat. Alpha 1 plus beta 1 stimulation induced contractile activity even when protein synthesis and hypertrophy were inhibited. Thus, the two alpha 1 responses could be dissociated, providing evidence for two independently-regulated cellular pathways for the dual alpha 1 trophic effects. One pathway leads to hypertrophy. The other, which requires concomitant beta 1 stimulation, controls the development of beating. Preliminary work raises the possibility that different products of inositol phospholipid hydrolysis might initiate the two alpha 1 trophic pathways. Other preliminary work suggests that the growth pathway is associated with the expression of specific genes and might reflect an action of the alpha 1-adrenoceptor on the cell nucleus. These studies define previously unsuspected trophic roles for the alpha 1-adrenergic receptor.
Explore the source record for details and available documents.
Catecholoestrogens are naturally occurring metabolites of oestrogens which are found in brain tissue and for which a neuroendocrine role has been postulated. However, reports of their effects on prolactin secretion are ambiguous and as yet no defined function has been attributed to them. The effects of 2-hydroxyoestradiol (2-OHE2) and dopamine on the release of prolactin in vitro by perfused pituitary glands from normal adult female rats at different stages of the oestrous cycle have been investigated. The purity and stability of the 2-OHE2 preparation before and after exposure to pituitary tissue was confirmed by radioenzymatic assay and subsequent thin-layer chromatography. Dopamine (500 nmol/l, 100 nmol/l) was found consistently to suppress release by 60%; this effect was immediate and reversible upon removal of the dopamine. In contrast, the effects of 2-OHE2 (10 nmol/l, 100 nmol/l) were found to vary during the cycle. No effect on prolactin release was evident during either dioestrus or pro-oestrus, but during oestrus a similar, though less potent, suppression of prolactin secretion to that of dopamine was observed (35% suppression compared with controls). The cyclical variation in the suppressive effect of 2-OHE2 on prolactin secretion in the female rat is compatible with a postulated neuroendocrine role for this catecholoestrogen.
After cryopreservation of semen from men with testicular tumours or Hodgkin's disease the success rate of artificial insemination of their partners was analysed. The cumulative probability of pregnancy at 6 months was 45%. The chance of pregnancy was greater when timing of ovulation was predicted with measurements of urinary luteinising hormone. Sperm density and sperm motility were also important in predicting the likelihood of pregnancy.
The activity of oestrogen-2/4-hydroxylase in brain tissue was studied using a radioenzymatic assay which controlled for non-specific formation of catechol oestrogen. The ontogeny of enzyme activity in male and female rat brain was examined between 1 and 70 days of age. Until 10 days of age, both sexes showed low enzyme activity. Between days 10 and 15 enzyme activity in the female significantly increased but was unchanged in the male. Male brain enzyme activity increased between days 15 and 20 whereas activity was unchanged in the female. Both males and females showed increases in enzyme activity between 20 and 25 days of age. Thereafter enzyme activity plateaued but at all ages between day 20 and day 70 male brain enzyme activity was significantly greater than in the female. A study of the distribution of the oestrogen-2/4-hydrolase in the sheep hypothalamus revealed that the stalk/median eminence had approx 10 times greater activity than either the anterior, medial or posterior hypothalamus. These findings are discussed in relation to sexual differentiation of the brain.
Patients with diabetes mellitus often exhibit abnormalities in plasma lipoprotein concentrations. We have examined the effect of glycemic control (as assessed by hemoglobin A1 levels) on the concentrations of plasma lipoproteins and apoproteins in 109 patients with type I diabetes mellitus. HbA1 levels showed positive correlations with plasma LDL-cholesterol levels (r = 0.31; P less than 0.002) and triglyceride levels (r = 0.41; P less than 0.002), but not with HDL-cholesterol levels. The strongest correlation was between HbA1 and plasma levels of apoprotein B (r = 0.57; P less than 0.001). We have also examined the effect of long-term improvement in glycemic control (achieved with insulin infusion pump therapy) on plasma lipoproteins in six patients with type I diabetes. Patients were followed for 5 to 12 months, with mean (+/- SD) HbA1c levels decreasing from 11.4 +/- 2.5 to 9.1 +/- 1.8. Most, but not all, patients showed reduction in plasma LDL-cholesterol levels and increase in plasma HDL-cholesterol levels, but these did not reach statistical significance. Only the decrease in plasma apo B levels was statistically significant (from 112 +/- 38 mg/dL before pump therapy to 91 +/- 33 mg/dL at the end of the follow-up, P less than 0.05). We conclude that glycemic control plays an important role in regulating the levels of plasma LDL-cholesterol and triglycerides in patients with type I diabetes. Apoprotein B is a particularly sensitive indicator to alterations in glycemic control. It is possible that tight glycemic control may have "antiatherogenic" effects through reduction of apo B levels.
Oestrogen-2/4-hydroxylase activity was measured in whole brain, thalamus, amygdala, hypothalamus and pituitary gland of lactating rats and in whole brain of rats on different days of the oestrous cycle. Enzyme activity was increased in whole brain and in each of the brain regions examined (with the exception of the amygdala) in lactating rats. This increase in enzyme activity was associated with an increase in serum prolactin levels. During the oestrous cycle, enzyme activity in whole brain was higher on metoestrus and dioestrus than on pro-oestrus and oestrus. The decrease in enzyme on pro-oestrus was associated with an increase in both serum oestradiol and prolactin levels. These results are consistent with the hypothesis that changes in oestrogen-2/4-hydroxylase activity are associated with changes in prolactin and oestradiol secretion and may play a regulatory role in reproduction.