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Biomedical subjects

M Donovan

Publications and source records attributed to M Donovan.

At least 73 records · Page 4Linked to original sources

A novel acid proteinase released by hybridoma cells.

An acid proteinase has been detected in culture supernate of the 9.2.27 murine hybridoma. This enzyme extensively degrades albumin and transferrin during short incubations at pH 3 and below. Limited proteolysis of the 9.2.27 IgG2a appears to occur in the culture supernate. Proteolysis in enhanced at low pH in the presence of urea or 1 M acetic acid. The proteinase activity accumulates in continuous perfusion, total cell recycle cultures, beginning during exponential growth of the hybridoma. It is destroyed by boiling and blocked by pepstatin, but not by inhibitors of cysteine or serine proteinases or by EDTA. The low pH optimum may distinguish this enzyme from the known rat and mouse aspartic acid proteinases including cathepsin D and cathepsin E.

Albumins↗

Serum PAF acetylhydrolase increases during neonatal maturation.

Acetylhydrolase is an acid-labile, 43 kd protein that catalyzes the degradation of platelet activating factor (PAF), a potent phospholipid inflammatory mediator, to its biologically inactive metabolite lysoPAF. PAF has a short half-life, thus acetylhydrolase plays an important role in its regulation. Since previous work suggests that PAF may be involved in certain neonatal diseases such as necrotizing enterocolitis, we studied the effect of age on acetylhydrolase activity. Serum acetylhydrolase activity was quantified using radio-labelled PAF and measuring reaction products. Serum samples were obtained prospectively from 70 subjects ranging in age from 4 hr to 48 yr. Acetylhydrolase activity was lower for newborns (less than 3 wk) than all other age ranges (8.2 +/- 1.4 nmole/ml/min vs 30.0 +/- 1.6 nmole/ml/min, p less than .01). Furthermore, enzyme activity increased linearly with respect to the natural logarithm of age from 0 days to 6 weeks (r = 0.65, p less than .001). By 6 weeks of life acetylhydrolase activity approached values of older children and adults. Newborn acetylhydrolase activity was similar between term and preterm infants (8.6 +/- 1.9 nmole/ml/min vs 7.2 +/- 2.4 nmole/ml/min, p = NS). We conclude that acetylhydrolase activity is low in human neonates and increases during the first 6 weeks of life. These results suggest that newborn infants may be at increased risk for pathophysiologic processes mediated by PAF.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Effects of intravenous xylazine hydrochloride on blood glucose, plasma insulin and rectal temperature in neonatal foals.

The effects of intravenous xylazine hydrochloride on blood glucose, plasma insulin and rectal temperature were investigated in six foals at 10 and 28 days of age. These variables were also measured in three foals at 19 days of age when saline alone was injected. Rectal temperature fell significantly after 30 mins in both groups of xylazine treated foals and was still depressed after 120 mins. Hypothermia did not occur in the saline control group. There was no significant change in blood glucose or plasma insulin concentrations during the 120 mins following either xylazine or saline administration and no significant differences between the three groups of foals. When foals were allowed to suckle after being away from their dams for 2 h, there was a significant (P less than 0.01) rise in plasma insulin levels in all the groups. Blood glucose showed a concomitant rise but this was only significant in the saline group. Unlike adults, intravenous xylazine (1.1 mg/kg) does not produce hypoinsulinaemia and hyperglycaemia in foals. This study suggests that the inhibition of insulin release from pancreatic beta-cells by xylazine, which in adults is alpha 2-adrenoceptor mediated, is immature or absent in foals under one month of age.

Animals↗

What we need to change about nursing. Staff nurses share their ideas.

New ways of structuring the delivery of nursing care, recruitment strategies, and retention programs are consistently needed if quality healthcare is to be preserved. The experience described in this article suggests that staff nurses propose creative and pragmatic solutions that enhance those of their managers. The author presents the recommendations of a task force designed to address the challenge of the nursing shortage in order to stimulate similar innovative activities in other settings.

Attitude of Health Personnel↗

Day-to-day variability of serum cholesterol, triglyceride, and high-density lipoprotein cholesterol levels. Impact on the assessment of risk according to the National Cholesterol Education Program guidelines.

The National Cholesterol Education Program has recently published guidelines for the assessment of cardiovascular risk and goals for laboratory accuracy. To test the impact of biologic and analytic variability on the ability of a single lipid measurement to assess risk accurately, lipids were measured on three occasions in 51 volunteers. Notable day-to-day variability of total cholesterol (5%), triglyceride (20%), high-density lipoprotein cholesterol (10%), and calculated low-density lipoprotein cholesterol (8%) levels was found. Analytic variability contributed significantly to total variability of high-density lipoprotein cholesterol levels and calculated low-density lipoprotein cholesterol levels. Confidence intervals constructed around National Cholesterol Education Program cutoff points suggested that classification was reliable from a single measurement if total cholesterol value was below 4.78 (less than 185 mg/dL), between 5.56 and 5.81 (215 and 225 mg/dL), or above 6.59 mmol/L (greater than 225 mg/dL). Low-density lipoprotein cholesterol value classification from a single measurement was only accurate at below 3.00 (greater than 116 mg/dL) or above 4.50 mmol/L (greater than 174 mg/dL). This study documents significant day-to-day variability of serum lipids and suggests that patients near the National Cholesterol Education Program cutoff points may require repeated measurements to assign risk accurately.

Adult↗

Early behaviour, development and parenting in a very low birthweight infant group.

Thirty-seven mothers, their very low birthweight infants and a matched group of term infants of normal birthweight and their mothers were seen when the infants were 12 months old (corrected for prematurity). Data were collected about infant behaviour and development, mother-infant interaction in a free-play situation, and parenting behaviour indicating child-centred care. Findings for the mother-infant dyads in the two birthweight groups were compared to determine the extent to which the data supported possible outcomes of: differences in behaviour/development only, differences in behaviour/development compounded by disturbances of interaction or parenting, or interaction/parenting disturbances despite apparently normal behaviour and development. Results of this analysis indicated significantly poorer scores for the very low birthweight infants on measures of behaviour and development only. Recent reports that interactional problems, which commonly exist early on, resolve through a process of mother-infant adaptation are discussed in light of the findings of this study. The need to consider developmental problems and interactive failure jointly if early intervention is to be offered is also examined.

Child Behavior↗

Linkage disequilibrium of plasminogen polymorphisms and assignment of the gene to human chromosome 6q26-6q27.

Linkage disequilibrium was observed between newly identified DNA polymorphisms and a previously described protein polymorphism for plasminogen. This finding implies that the two types of polymorphisms describe variation at the same locus. The plasminogen gene was mapped to chromosomal bands 6q26-q27 using somatic-cell hybrids and in situ hybridization. Linkage disequilibrium between protein and DNA polymorphisms has utility in substituting for protein typing in instances where only DNA samples are available, such as from deceased individuals or extinct species. The technique may be useful when cross-hybridizing sequences make the interpretation of Southern blot patterns difficult and may obviate the need for extensive DNA sequencing. In some cases, disequilibrium may provide information useful for determining the appropriate direction for chromosome walks from a marker locus to a target locus.

Alleles↗

The structure of the chorion and associated surface filaments in Oryzias--evidence for the presence of extracellular tubules.

The structure of the chorion with its associated surface filaments has been examined in Oryzias latipes using several techniques, including scanning and transmission electron microscopy, enzymatic digestion, and sodium dodecylsulfate-polyacrylamide gel electrophoresis. The chorion of the recently fertilized egg was found to be organized into three zones: an outer, fuzzy electron-lucent zone that was continuous over the surface of filaments, a middle, homogeneous electron-dense zone, and an inner zone of ten to 12 horizontal, fibrous lamellae. Two topographically distinct types of filaments were found on the chorionic surface: nonattaching and attaching. Nonattaching filaments showed a regular spatial distribution over the chorion with an interfilament distance of about 60-70 microns. Attaching filaments originated from a localized portion of the chorion and united with those of neighboring eggs to anchor the egg cluster to the gonoduct of the female. Both nonattaching and attaching filaments were morphologically regionalized into basal and distal segments. Internally, nonattaching and attaching filaments were constructed of unbranched, packed tubules with an average outside diameter of approximately 19.5 and 18.8 nm, respectively. Using the attaching filament for further study, it was determined by rotational analysis (Markham et al., '63) that the wall of each tubule was a cylinder composed of 14 globular subunits. Two structural types of attaching filaments were identified. The type I attaching filament was similar in internal organization to the nonattaching filament and consisted of only tubules. The type II attaching filament, however, showed a highly osmiophilic, electron-dense bar surrounded by packed tubules. Tubules of attaching filaments of the adult were resistant to the action of Triton X-100 and colchicine, but sensitive to a 0.1% protease solution. However, colchicine-treated ovary tissue showed an absence and pattern of disorganization of tubules at the periphery of developing filaments. Solubilized attaching filament samples electrophoresed on 7.5% polyacrylamide-SDS gels were resolved into a pair of Coomassie-blue-positive bands that comigrated with purified porcine brain tubulin. The apparent molecular weight of the attaching filament polypeptide was determined to be approximately 55,000 daltons. These data suggest that the extracellular, tubular components of attaching filaments (as well as nonattaching filaments) are proteinaceous and show properties similar to those of cytoplasmic microtubules. Tubular precursor material was electron-dense and appeared to originate in the cisternae of the rough endoplasmic reticulum of ovarian foll

Animals↗

Effects of D-valine on pulmonary artery endothelial cell morphology and function in cell culture.

The effects of D-valine on the cell culture of bovine pulmonary artery endothelial cells were studied using D-valine-modified Minimal Essential Medium (MEM). D-Valine-treated cultures (46-920 mg/l) were compared with replicate cells grown in L-valine (46 mg/l)-MEM. All media were supplemented with 15% fetal bovine serum (FBS). Endothelial cells were grown for 14 passages with split ratios varying from 1:3 to 1:6. Unlike cells grown in L-valine MEM, cells grown in D-valine MEM did not become contaminated by the growth fibroblasts in primary cultures. D-Valine-treated cells were found to grow in cobblestone array, exhibit contact inhibition and strongly express factor-VIII antigen (F-VIII). D-Valine-grown cells produced PGI2 in greater proportion to PGE2, both constitutively and when stimulated by bradykinin, on comparison with cells grown in L-valine. In addition, cells grown in L-valine, although able to express factor VIII, were not comparable to D-valine cells with respect to other parameters assayed (morphology and growth as a monolayer).

Animals↗

Uptake of ferritin by the mosaic egg surface of Brachydanio.

The internalization of membrane from the mosaic egg surface of the zebra fish, Brachydanio, was investigated using anionic ferritin and transmission electron microscopy. The cortical cytoplasm of the 5-min activated egg showed numerous membrane-bound vesicles not found in the unactivated egg cortex. Two types of vesicles were identified: uncoated (smooth) and coated. Coated vesicles measured about 0.7 to 0.9 micrometer in diameter. Coated pits, considered to be precursors to the formation of coated vesicles, were frequently observed at the base of membrane-lined cortical granule crypts. Anionic ferritin was localized over coated pits and in both smooth and coated vesicles. The absence of any morphological evidence of a surface origin for smooth vesicles suggested these ferritin-labeled organelles might be formed by coated vesicle fusion. Our results indicate that the plasma membrane redundancy created by the exocytosis of cortical granules in Brachydanio appears to be resolved in part by the internalization of membrane through endocytosis.

Animals↗

Cancer pain: you can help!

Pain exists because electrical impulses travel along a series of nerves from "where it hurts" through the gate in the spinal cord and through the thalamus to the areas of the brain where thinking, feeling, and action are controlled. Along this path are several "switches" that can adjust the pain, or turn it down as one would the volume of a radio. Figure 5 summarizes the interventions that have been discussed in this article in relation to these four switches. One can use a moderate to large amount of a single intervention (such as medication) to shut off the pain; or one can use small to moderate amounts of a combination of interventions to accomplish the same or greater level of comfort. In most situations, a combined approach provides the patient with better control of pain, a more active role in his care, fewer side effects, and less dependence on others.

Analgesia↗

Cardiovascular responses to autonomic blockade in hypoxemic fetal lambs.

The cardiovascular responses of 11 fetal lambs in utero to hypoxemia were evaluated before and after autonomic blockade. Hypoxemia was produced by lowering the maternally inspired oxygen or by progressive constriction of the umbilical cord by a cuff occluder. The animals were studied serially from 112 days' gestation to term. Fetal carotid arterial pO2 fell from 24 to 12 torr and was accompanied by a 35% decline in heart rate and 32% rise in blood pressure. Parasympathetic blockade with atropine produced a 114% increase in heart rate in the hypoxemic fetuses compared to 26% in the normoxemic controls. Pretreatment with atropine prevented the hypoxemia-induced bradycardia without altering the hypertensive response. alpha-Adrenergic blockade resulted in a 22% decrease in blood pressure in the hypoxemic group, three times greater than the controls. Pre-hypoxemia alpha-blockade prevented the hypertension without affecting the fall in fetal heart rate. It is concluded that fetal bradycardia in response to hypoxemia is due to a direct increase in parasympathetic activity rather than secondary to a hypertension-induced baroreflex. The alpha-mediated increase in systemic vascular resistance and blood pressure may be a compensatory mechanism to maintain placental blood flow despite the decline in combined ventricular output.

Animals↗

Retinoid binding proteins-expression patterns in the human placenta.

The present study examined the expression and occurrence of different retinoid binding proteins in human first trimester and term placenta. At both stages, messenger RNA for the serum transport vehicle for retinol, retinol-binding protein (RBP), was detected only in decidual cells of the basal plate. In contrast, immunoreactive RBP (irRBP) was present in syncytiotrophoblast, core mesenchyme and lumen of vessels in placental villi and in mesenchyme and decidual cells of the basal plate. In villi of term placentae, however, staining for irRBP was lost in syncytiotrophoblasts and villous core mesenchyme. A putative placental RBP-receptor, approx 60-65kDa, was detected in the villous syncytiotrophoblast of both stages investigated. Immunoreactivity for the cellular retinol binding protein type I (CRBP I), was found in villous stromal cells and in decidual cells of the basal plate in sections of first trimester and term placenta. These results may suggest that maternal RBP-retinol is transferred across the chorionic villi to the fetal/villous circulation and that villous absorption of the complex is mediated via a placental RBP-receptor. Moreover, binding and possibly also metabolism of retinol may occur in the CRBP I positive villous stromal cells and decidual cells of the basal plate. In the latter, release of placental RBP-retinol may also be anticipated.

Allantois↗