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Biomedical subjects

M C Neville

Publications and source records attributed to M C Neville.

At least 37 records · Page 2Linked to original sources
PubMed1999

Mouse mammary gland xanthine oxidoreductase: purification, characterization, and regulation.

Xanthine oxidoreductase (XOR) has been purified from lactating mouse mammary tissue and its properties and developmental expression have been characterized. XOR was purified 80-fold in two steps using benzamidine-Sepharose affinity chromatography. The purified enzyme had a specific activity of 5.7 U/mg and an activity to flavin ratio of 192. SDS-polyacrylamide gel electrophoresis showed that it was composed of a single (150 kDa) band and N-terminal sequence analysis verified that it was intact mouse XOR. Isoelectric focusing showed that purified XOR was composed of three catalytically active, electrophoretic variants with pI values of 7.55, 7.65, and 7.70. The majority of the XOR activity in both pregnant and lactating mammary glands was shown to exist as NAD+-dependent dehydrogenase (XD form), while the enzyme in freshly obtained mouse milk exits as O2-dependent oxidase (XO form). The activity and protein levels of XOR selectively increased in mammary tissue during pregnancy and lactation. The time course of these increases was biphasic and correlated with the functional maturation of the mammary gland. These results indicate that XOR may have novel, mammary gland-specific functions, in addition to its role in purine metabolism.

Amino Acid Sequence↗
PubMed1999

Adaptation of maternal lipid flux to pregnancy: research needs.

Adaptations of maternal lipid metabolism during pregnancy are directed toward both the needs of the fetus for lipid substrates and maternal requirements for lipid stores serving as energy reserves for lactation. The mechanisms are poorly understood, but must be elucidated before new dietary recommendations can be made about dietary supplementation with long-chain polyunsaturated fatty acids (LC-PUFA). Problems of high priority for research are: (1) Fetal requirements for specific fatty acids, including essential fatty acids (EFA) and long-chain polyunsaturated fatty acids (LC-PUFA); (2) The mechanisms for transfer of fatty acids across the placenta; (3) The role of very low density lipoproteins (VLDL) in transfer of EFA and LC-PUFA from the maternal liver to the placenta; (4) Adjustments of fatty acid metabolism in the maternal liver during pregnancy; and (5) The effect of dietary LC-PUFA on maternal fatty acid metabolism during pregnancy.

Adaptation, Physiological↗
PubMed1999

Report of the IDECG Working Group on the modulating effect of stressors on the upper and lower limits of lipid and carbohydrate intake. International Dietary Energy Consultative Group.

The recommended caloric intake should be increased by 2870kJ (670Kcal)/d in the exclusively breast-feeding woman. Of this increase, 10% should be ingested as protein, up to 50% as lipid and no less than 40% as carbohydrate. If weight loss is desired lipid intake can be reduced but carbohydrate intake should be maintained. Of the total energy increment 3% should be supplied by essential fatty acids (linoleic and alpha-linolenic acids) and 0.5% by n-3 fatty acids. The issue of dietary supplementation with long-chain polyunsaturated fatty acids remains for future research.

Dietary Carbohydrates↗
PubMed1999

Breast-feeding, mastitis, and HIV transmission: nutritional implications.

In many developing countries, transmission of the human immunodeficiency virus (HIV) from mother to infant occurs through breast-feeding. Mastitis, an inflammatory process in the breast, may be common in lactating women in Africa and is associated with both higher HIV load in breast milk and mother-to-child transmission of HIV. Antioxidant micronutrient deficiencies may increase the risk of mastitis. Whether prevention, early diagnosis, and prompt treatment of mastitis will help reduce mother-to-child transmission of HIV in breast-feeding women needs further study.

Animals↗
PubMed1999

Physiology of lactation.

The physiology of human lactation is described with secretions on mammary gland anatomy and development, the mechanisms of milk secretion and ejection, and the temporal sequence of events during the transition from pregnancy to lactation (lactogenesis). Finally, interactions between lactation and maternal metabolism are briefly described and the interaction of lactation with fertility discussed.

Animals↗
PubMed1998

Tight junction regulation in the mammary gland.

Tight junctions form a narrow, continuous seal that surrounds each endothelial and epithelial cell at the apical border, and act to regulate the movement of material through the paracellular pathway. In the mammary gland, the tight junctions of the alveolar epithelial cells are impermeable during lactation, and thus allow milk to be stored between nursing periods without leakage of milk components from the lumen. Nonetheless mammary epithelial tight junctions are dynamic and can be regulated by a number of stimuli. Tight junctions of the mammary gland from the pregnant animal are leaky, undergoing closure around parturition to become the impermeable tight junctions of the lactating animal. Milk stasis, high doses of oxytocin, and mastitis have been shown to increase tight junction permeability. In general changes in tight junction permeability in the mammary gland appear to be the results of a state change and not assembly and disassembly of tight junctions. Both local factors, such as intramammary pressure and TGF-beta, and systemic factors, such as prolactin, progesterone, and glucocorticoids, appear to play a role in the regulation of mammary tight junctions. Finally, the tight junction state appears to be closely linked to milk secretion. An increase in tight junction permeability is accompanied by decrease in the milk secretion rate, and conversely, a decrease in tight junction permeability is accompanied by an increase in the milk secretion rate.

Animals↗
PubMed1998

The mammary fat pad.

The mammary fat pad is essential for development of the mammary epithelium, providing signals that mediate ductal morphogenesis and, probably, alveolar differentiation. The "cleared" fat pad is often used as a transplantation site. Considering the crucial role of the fat pad, its properties have received relatively little attention from researchers in the field. Some of the questions whose investigation is pertinent to understanding both normal mammary development and carcinogenesis are outlined in this commentary in the spirit of stimulating enquiry into this important subject. It is clear from a brief perusal of the available literature that until studies are specifically designed to clearly differentiate between functional effects of the fibrous and the adipose stroma, more substantive information about their differential effects on mammary development and tumorigenesis will not be forthcoming.

Adipose Tissue↗
PubMed1997

Regulation of milk lipid secretion and composition.

Triacylglycerols make up 98% of the lipid content of milk, ranging in different species from 0 to 50% of the total milk volume. The fatty aid composition of the triacylglycerols depends on the species, the dietary fatty acid composition, and the carbohydrate-to-lipid ratio of the diet. The rate of lipid synthesis in the lactating mammary gland depends on the stage of mammary development and is decreased by fasting and starvation in ruminants and rodents but not in species that fast during lactation, such as seals and hibernating bears. Regulatory agents include insulin, prolactin, and non-esterified fatty acids. Dietary trans fatty acids may depress milk lipid synthesis under certain conditions. Evidence is presented that fatty acids may play a major regulatory role in acute changes in de novo mammary fatty acid synthesis, acting primarily on the activity of acetyl coenzyme A carboxylase.

Animals↗
PubMed1997

Active transport of nitrofurantoin across the mammary epithelium in vivo.

Nitrofurantoin is a commonly used urinary tract antibiotic that has been found at high concentrations in human milk. In vivo studies in rats were carried out to determine the mechanism by which this drug crosses the mammary epithelium. Lactating rats were gavage-fed with nitrofurantoin, and their milk and plasma levels of the antibiotic were measured at intervals up to 8 hr. The average milk-to-plasma (M/P) ratio, calculated from the areas under the milk and plasma curves, respectively, was 23 compared with a ratio predicted to be about 0.3 on the basis of lipid partitioning and protein binding determinations. M/P ratios for two nitrofurantoin congeners were also calculated. The neutral compound furazolidone had a M/P ratio of about 1, as predicted, whereas the basic compound furaltadone had a M/P ratio of 3.49 compared with a predicted ratio of 1.4. These data suggest that nitrofurantoin and, to a lesser extent, furaltadone are actively transported across the mammary epithelium into milk.

Administration, Oral↗
PubMed1997

Active transport of nitrofurantoin across a mouse mammary epithelial monolayer.

The antibiotic nitrofurantoin is transported against an electrochemical gradient into milk. A monolayer of CIT3 cells, a subline of the Comma 1D normal mouse mammary epithelial cell line, transports [14C]-nitrofurantoin against a concentration gradient from the basal to the apical solution when grown on membrane filters. In a side-by-side diffusion chamber with well-stirred solutions on both sides, the transfer rate is 50% higher in the basal-to-apical than in the apical-to-basal direction. Nonlabeled nitrofurantoin (500 microM) in the basal chamber equalized the transport in both directions, suggesting that a specific transporter is responsible for the basal-to-apical increment in flux. From inhibition studies, the apparent affinity of this transporter for nitrofurantoin is 50 microM. Changes in pH between 6.4 and 7.8 had no effect on the active transport component of the flux but did affect the passive flux component. Passive flux of the nonionized molecule was 2.6 times faster than that of the ionized molecule, but the ionized molecule did appear to cross the membrane passively. Our findings show that nitrofurantoin is actively transported across a mammary epithelial cell monolayer by a transporter whose affinity for nitrofurantoin does not depend on the anionic charge on nitrofurantoin. The pH dependence of a parallel passive pathway suggests that both nonionized and ionized forms of nitrofurantoin cross the membranes of the mammary epithelial cell by passive diffusion.

Animals↗
PubMed1995

Effects of xenobiotics on milk secretion and composition.

Xenobiotics have the potential of disrupting the differentiated function of the mammary gland, that is, milk secretion, by inhibiting mammary development, by directly interfering with the secretory function of the mammary alveolar cell, by altering the hormonal milieu that supports lactation, or by impeding nutrient transport to the mammary cell. Although solid information is lacking in most of these areas, available research suggests that antiestrogens may interfere with mammary development, that oxidants and phorbol esters may inhibit milk secretion, that ergot alkaloids and alcohol may alter the hormonal milieu, and that dioxins may interfere with lipid transport to the mammary gland. Models for the investigation of these and other environmental toxins and drugs are suggested.

Animals↗
PubMed1994

Regulation of lipoprotein lipase activity and mRNA in the mammary gland of the lactating mouse.

We examined the effects of reproductive stage and fasting on lipoprotein lipase (LPL) activity and mRNA in the mouse mammary gland. Heparin-releasable and cell-associated LPL activity rose immediately after birth, followed 1-2 days later by an increase in LPL mRNA. Fasting decreased LPL activity in the mammary gland at all reproductive stages. During lactation, both milk and heparin-releasable LPL were substantially decreased by an overnight fast, whereas cell-associated LPL was less affected and LPL mRNA did not change. These studies indicate that the extracellular, heparin-releasable, fraction of mammary LPL activity responds most rapidly to alterations in physiological state, usually accompanied by smaller changes in cellular enzyme activity. Changes in the level of LPL mRNA were seen only during the transition from pregnancy to lactation, and these tended to follow, rather than precede, changes in enzyme activity. We conclude that in the mammary gland as in adipose tissue, LPL is regulated primarily at the translational and post-translational level.

Adipose Tissue↗
PubMed1994

Calcium partitioning in human and bovine milk.

The partitioning of calcium in human milk was studied experimentally and compared with the distribution of calcium among the compartments of bovine milk. Care was taken to handle the milk samples to produce minimal disturbance of the milk fat globule membranes and the CO2 content. About 15% of the milk calcium was associated with casein in human milk; the remainder was in the aqueous phase. The equilibrium between ionized calcium and calcium complexes with smaller anions was examined. Ionized calcium varied between 2.3 and 4.0 mM across individuals (mean 3.0 +/- .1 mM) at 90 d of lactation. The remainder of the calcium in the aqueous phase was associated with citrate and phosphate. Changes in total calcium in human milk during lactogenesis and late lactation reflected changes in citrate and casein rather than alterations in ionized calcium.

Animals↗
PubMed1993

Effects of fasting, elevated plasma glucose and plasma insulin concentrations on milk secretion in women.

In order to determine whether short term variations in plasma glucose and/or insulin influence milk lactose secretion in women, the effects of fasting and increased blood insulin and glucose on milk volume and composition were studied with glucose clamp methodology in exclusively and partially breast-feeding women. Twenty hours of fasting had no discernable effect on the output of milk or its macronutrient composition. Four hours of increased plasma insulin, studied under conditions where plasma glucose was maintained at the fasting level, had no effect on milk volume, milk glucose concentration, total fat content or lactose secretion rate. Increased plasma glucose, maintained at twice fasting levels for 4 to 6 h, produced a threefold increase in milk glucose concentration but had no significant effect on the rate of lactose synthesis. In partially breast-feeding women producing no more than 200 ml milk per day, a similar degree of hyperglycaemia increased milk glucose more than fourfold but did not significantly increase the milk secretion rate. It is concluded that human milk production is isolated from the homeostatic mechanisms that regulate glucose metabolism in the rest of the body, in part because the lactose synthetase system has a Km for glucose lower than the concentration available in the Golgi compartment.

Adult↗
PubMed1991

Studies in human lactation: milk composition and daily secretion rates of macronutrients in the first year of lactation.

Time-dependent changes in milk composition and secretion from pregnancy through greater than or equal to 6 mo of exclusive breast-feeding were studied in 13 multiparous women. Concentrations and secretion rates of lipid, lactose, protein, sodium, chloride, potassium, total calcium, ionized calcium, magnesium, glucose, citrate, inorganic phosphate, creatinine, and urea and pH were analyzed longitudinally from day 6 until weaning commenced. The composition of the antepartum secretion was related to the permeability of the junctional complexes between mammary cells. Significant increases in lactose, glucose, pH, and ionized calcium and significant decreases in protein, sodium, potassium, chloride, and calcium concentrations were observed between 1 and 6 mo. Significant differences among individuals, which persisted through lactation, were observed for the concentrations of sodium, potassium, chloride, and inorganic phosphate. The amount of lactose, ionized calcium, and magnesium transferred to the infant was also characteristic of each mother-infant pair. Our data imply that lactation performance is determined in the first month postpartum.

Breast Feeding↗
PubMed1991

Studies in human lactation: milk volume and nutrient composition during weaning and lactogenesis.

Concentrations and secretion rates of macronutrients and major ions in human milk during lactogenesis (birth to 8 d) and late lactation (greater than 6 mo postpartum) are reported. Postpartum changes in lactose, sodium, and chloride concentrations signalled closure of the paracellular pathway during days 1-2. From days 2 to 4 postpartum, initiation of copious milk secretion was accompanied by significant increases in citrate, free phosphate, glucose, and calcium concentrations and a decrease in pH. During weaning, significant changes in milk protein, lactose, chloride, and sodium concentrations were observed only when milk volume fell below 400 mL/d; more than one feed per day was necessary to maintain milk secretion. Temporal changes in the concentration of other milk components, except glucose and magnesium, were not different in weaning and non-weaning women. Differences between the relation of milk volume and composition during lactogenesis and weaning suggest that volume is differently regulated in the two periods.

Citrates↗