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Biomedical subjects

M Peaker

Publications and source records attributed to M Peaker.

At least 91 records · Page 5Linked to original sources

Autotransplantation of the goat mammary gland.

The modified technique for transplanting one mammary gland of a lactating goat to the neck, with the mammary (pudic) artery and vein anastomosed to the carotid artery and jugular vein respectively, is described. This technique was successful in 6 operations and there were no significant differences between the milk yield of the transplanted and control (in situ) glands at any stage after operation. These results are compared with those from an earlier series in which no special provision was made for lymphatic drainage and in which anticoagulant therapy and treatment of the gland prior to attachment were not standardized.

Animals↗

Lactation in the rabbit: mammary blood flow and cardiac output.

In anaesthetized rabbits, cardiac output (C.O.) and its distribution to the mammary glands, heart, liver and kidneys have been determined in established lactation (11--13 days), later lactation (26--27 days) and in virgins. During lactation, the volume of circulating blood, C.O., mammary blood flow and mammary weight were significantly greater than in virgins. There were no significant differences in C.O. and % C.O. received by the mammary glands between established and late lactation, and no significant decrease in mammary blood flow in late lactation. The weights of the liver and kidneys were significantly increased in lactation but there were no significant differences in liver, heart (coronary) and kidney blood flow. The rate of growth of the young was positively and significantly correlated with % C.O. received by the mammary glands and mammary weight, but not with C.O. Strong correlation was also observed between the % C.O. received by the mammary glands and mammary weight. There were no significant differences in C.O., mammary % C.O. and mammary blood flow in animals in established lactation 2--3 h and 24 h after suckling (i.e. shortly after and just before suckling). By 48 h after the last suckling mammary blood flow and % C.O., but not C.O., were significantly decreased. Possible factors causing these changes are discussed. The results are discussed in relation to the change in milk composition that occurs in late lactation in this species and to the role and effects of prolactin. It is suggested that events occurring during lactation have different sensitivities to prolactin.

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The secretion of calcium and phosphorus into milk.

1. The time course of appearance of radioactivity in milk was studied following close-arterial infusion of labelled phosphate, Ca or leucine into the mammary artery of lactating goats. Maximum activities were reached at 1.5 hr in all milk fractions including inorganic soluble phosphate, inorganic colloidal phosphate, casein P, soluble Ca, protein-associated Ca and casein. 2. At 0.5 hr, labelling of the soluble and colloidal phosphate fractions was significantly higher than that of the casein P. 3. Recovery of 32P or 47Ca 3 or more hours after infusion into the cistern of the mammary glands was 98% or greater, indicating that the mammary epithelium is virtually impermeable to [32P]phosphate and 47Ca in the milk to blood direction. 4. Ca and P failed to enter milk in excess of the normal secretion rate when the milk was diluted with isosmotic sucrose given by intraductal injection. 5. These data suggest that milk Ca and phosphate in their various forms are secreted, like protein and lactose, by exocytosis of Golgi vesicles. Unless a paracellular pathway is present, as in oxytocin-treated animals, the milk concentrations are maintained by virtue of the impermeability of the mammary epithelium to these substances.

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Adaptive hyperplasia and compensatory growth in the salt glands of ducks and geese.

1. The incorporation of [3H]thymidine into salt-gland DNA has been studied in vivo and in vitro during adaptation of birds to salt water. 2. No increase in [3H]thymidine incorporation in vivo was apparent in birds on salt water for 0.25 and 1 day compared with those on fresh water. However, by 2 days there was a marked increase. At 7 and 14 days, incorporation was again low but by these later stages the DNA content of the glands was significantly increased. 3. Increased incorporation of [3H]thymidine was also evident in salt-gland slices incubated in vitro from birds on salt water for 2 or 4 days, but not for 14 days, compared with those on fresh water. 4. It is concluded that hyperplasia, as well as the hypertrophy demonstrated previously, occurs as part of the over-all adaptive response of the salt glands during the continual ingestion of salt water, but that the time course of the two processes is different. 5. In geese with one salt gland removed, no indication of compensatory growth of the remaining gland was evident in birds kept on fresh water for 24 days. In such birds on salt water for 14 days, some compensatory growth occurred but, as judged by measurements of DNA, RNA and protein, this could be ascribed to hypertrophy.

Adaptation, Physiological↗

Changes in mammary development and composition of secretion during late pregnancy in the mare.

Small samples of mammary secretion were taken for analysis from Thoroughbred mares during the last 3 weeks of pregnancy up to the time of foaling. The concentrations of sodium and chloride decreased while those of lactose, potassium, citrate, phosphate, calcium, magnesium and protein increased. The time-course of these changes showed marked variation between animals. The concentration of whey proteins began to increase about 10 days before parturition. The appearance of the secretion and the size of the mammary glands increased in the last few days of pregnancy. It is suggested that the concentration of calcium in mammary secretion could provide the basis of a test for impending parturition in this species.

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Changes in mammary function at the onset of lactation in the goat: correlation with hormonal changes.

1. Changes in mammary function and plasma hormone concentrations during late pregnancy and the onset of lactation have been studied in conscious goats.2. Mammary blood flow, oxygen consumption and glucose uptake increased markedly and significantly between 2 days and 0.5-1 day pre-partum.3. The increase in mammary glucose uptake was relatively greater than that of oxygen consumption or blood flow.4. The concentration of citrate in mammary secretion increased; the first significant change was apparent 0.5-1 day pre-partum but the main rise occurred after this time.5. It is concluded that the marked increase in mammary glucose uptake 0.5-1 day before parturition indicates the time of onset of copious milk secretion.6. The first significant increase in the concentration of unconjugated oestrogens in arterial plasma occurred 3 days pre-partum, whereas the first significant decrease in progesterone and increase in 13,14-dihydro-15-oxoprostaglandin F(2alpha) occurred 0.5-1 day pre-partum, thus coinciding with the mammary changes; there was also a peak in prolactin concentrations at the latter time.7. The hormonal changes are discussed in relation to current concepts of the initiation of parturition and the onset of copious milk secretion in this species. It is suggested that the fall in plasma progesterone concentrations triggers milk secretion at high rates.

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Mammary function and its control at the cessation of lactation in the goat.

1. The changes in mammary function following cessation of milking during declining lactation have been studied in conscious goats. 2. No significant changes in the rate of milk secretion, mammary blood flow or metabolism occurred in the first 24 h after cessation of milking. After then, secretory rate, mammary blood flow, oxygen consumption, glucose uptake and acetate uptake decreased markedly over the next 3 days. Up to the time of maximum udder distension on day 3, there were no major changes in milk composition. 3. It was found that the rate of milk secretion declined when the calculated pressure within the alveoli became positive. 4. After 3 days, mammary volume and intramammary pressure decreased, and the composition of milk changed slowly to resemble that of extracellular fluid, i.e. [Na+], [Cl-], [HCO3-] and pH increased while [K+], [lactose] and [citrate] decreased. During this time [lactose] and [K+] were positively correlated, and [lactose] and [Na+], and [lactose] and [Cl-] negatively correlated. 5. It is suggested that the changes in milk composition, the decreases in mammary volume and in intramammary pressure after day 3 are due to the loss of integrity of the mammary epithelium. 6. By about 7 weeks after the cessation of milking the udder volume was less than the empty udder volume before milking was stopped, indicating a loss of mammary tissue as well as the resorption of fluid. 7. When milking of an autotransplanted gland was stopped, while milking of the control gland in situ was continued, the rate of secretion in the transplant fell while that of the control did not change. 8. In goats milked normally but in which a volume of isosmotic lactose equal to the volume of milk removed at that milking was injected into the lumen of one gland at each milking, the rate of secretion of that gland, but not that of the other, decreased.

Acetates↗

Mechanism of milk secretion: milk composition in relation to potential difference across the mammary epithelium.

1. In conscious lactating goats a significant correlation was found between blood-milk potential difference (p.d.) and milk [lactose] such that in goats with a lower milk [lactose], milk was more negative with respect to blood.2. When mannose was substituted for glucose in the substrate mixture of isolated perfused goat mammary glands, milk yield and milk [lactose] fell while milk [Na] and [K] increased; in parallel experiments the blood-milk p.d. changed such that milk became more negative with respect to blood. These changes were reversed following the addition of glucose.3. When milk was made hypertonic by the addition of hyperosmotic sucrose or lactose solutions, water entered milk osmotically and milk became electrically less negative or even positive with respect to blood in goats, cows and guinea-pigs.4. No effect on p.d. was apparent following the addition of isosmotic sucrose to milk in goats.5. When milk was held in the teat of goats by a pneumatic cuff around the base of the teat, no effect on p.d. was apparent when hyperosmotic sucrose was introduced into this teat pouch.6. It is suggested that waterflow-induced potentials (the streaming potential and the transport number effect) can be induced across the mammary epithelium.7. In goats exogenous oxytocin lowered milk [lactose] and blood-milk p.d. became less negative with respect to blood.8. In non-lactating and mastitic glands of goats the blood-milk p.d. was within 0.5-2.5 mV of zero.9. The effects of oxytocin, and the low p.d. in non-lactating and mastitic glands, are compatible with the view that in such circumstances there is a paracellular pathway across the mammary epithelium which partially short-circuits the two sides.10. It is suggested that, with water being drawn osmotically into milk to dilute newly formed lactose, waterflow-induced potentials may be responsible for establishing the normal p.d. across the apical membrane of the secretary cell, thereby keeping milk [K] and [Na] lower than in intracellular fluid.

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Lactation: some cardiovascular and metabolic consequences, and the mechanisms of lactose and ion secretion into milk.

Lactation causes increases in mammary blood flow, gastrointestinal blood flow and cardiac output in the rat, and the suckling-induced release of lactogenic anterior pituitary hormones probably causes these changes, directly or indirectly. Metabolic requirements of lactation in women are similar to those in other animals not artificially selected for a high milk yield but the physiological control of the relationship between milk secretion and nutrient availability is not well understood. The unusual composition of the aqueous phase of human milk (rich in lactose but poor in sodium and potassium ions) can be explained by the same basic mechanisms for secretion of lactose and ions as operate in other animals but with quantitative differences.

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The secretion of citrate into milk.

1. The time course of changes in specific activities of citrate, lactose and fatty acids in milk during frequent milking, following the I.V. administration of labelled glucose, acetate and chylomicrons in goats has been studied. Peak specific activities of lactose and citrate in milk were reached at 2-3 hr, while peak specific activites of fatty acids were reached at 5-7 hr. 2. Following short I.A. infusions of 24Na, 36Cl, and 42K, peak specific activities in milk were reached in 1 hr or less. 3. The mammary epithelium of lactating goats was found to be virtually impermeable to labelled citrate in both directions. 4. Labelled citrate had an apparent volume of distribution in lactating guinea-pigs mammary slices in vitro similar to that of extracellular space markers. 5. Treatment of goats with large doses of oxytocin markedly increased the permeability of the secretory epithelium to labelled citrate. 6. In the goat mammary gland, citrate, protein and calcium failed to enter milk which had been diluted with isosmotic lactose by intraductal injection, whereas Na, K and Cl did enter, thus tending to restore the concentrations of these ions to normal. 7. It is suggested that citrate, which is formed within the sucretory cell, enters milk not by passage across the apical cell membrane but, in common with lactose and milk protein, by exocytosis of Golgi vesicles. It appears that citrate is held at high concentrations in milk by virtue of the impermeability of the mammary epithelium to the forms in which it occurs in milk.

Animals↗

The distribution and movements of carbon dioxide, carbonic acid and bicarbonate between blood and milk in the goat.

1. A-V differences and milk concentrations of respiratory gases, pH, HCO3 and H2CO3 have been measured in lactating goats and cows. 2. The pH and [HCO3 minus] of milk were significantly lower than those of plasma while milk PCO2 was virtually identical to that of mammary venous blood. [H2CO3+ dissolved CO2] was similar in milk and blood. 3. 14-C (from injected [14-C]HCO3 minus was found to cross the mammary epithelium in both directions. 14-C also passed across the duct epithelium and since this epithelium has previously been shown to be impermeable to ions it is argued that 14-C crossed in an unionized form, i.e. as CO2 and/or H2CO3. 4. Hourly milking with the aid of oxytocin raised milk pH, [HCO3 minus], [H2CO3], [Na] and E1Cl], and lowered [K], [lactose] and [phosphate]. These effects are discussed in relation to the hypothesis proposed previously for the action of oxytocin on milk composition. 5. A scheme for the distribution and movements of CO2, H2CO3 and HCO3 minus between extracellular fluid and milk is suggested, and discussed in relation to Cl minus transport.

Animals↗

The control of adaptive hypertrophy in the salt glands of geese and ducks.

1. Factors controlling adaptive hypertrophy, which occurs when marine, or potentially marine, birds drink salt water, have been investigated in geese and ducks using changes in salt-weight weight, RNA and DNA contents as indices of this process. 2. Unilateral post-ganglionic denervation in geese prevented the changes in [RNA] and [RNA]:[DNA] that occurred in the intact gland of birds given salt water for 24 hr; denervation had no significant effect in birds on fresh water throughout. 3. Atropine treatment also prevented the adaptive changes in geese given salt water. 4. In ducks give 0.3 M-NaCl for 48 hr salt-gland weight, [RNA] and [RNA]:[DNA] increase markedly. Treatment of ducks drinking fresh water with large doses of corticosterone and mammalian ACTH for 48 hr had no significant effects on salt-gland weight, RNA or DNA; mammalian prolactin treatment for 48 hr significantly raised [RNA]. 5. No changes in the total amount of DNA in the glands were observed in these experiments, thus indicating that hyperplasia does not occur within 48 hr of a bird first drinking salt water. 6. It is concluded that adaptive hypertrophy is controlled by secretory nerves, and that hormones, if they play any part in this process, have a permissive or secondary role. It is suggested that hypertrophy and the maintenance of the secretory cells in the fully-adapted state may be obligatorily related to secretory activity induced by cholinergic secretory nerves.

Adaptation, Physiological↗

Secretory activity of goat mammary glands during pregnancy and the onset of lactation.

1. The volume of the udder and the composition of the secretion have been followed in five goats through pregnancy to the onset of lactation. 2. During the middle of pregnancy udder volume was minimal and there was little or no fluid in the teats. 3. Two stages of commencing secretory activity (lactogenesis) were defined. In the first, starting up to ten weeks pre-partum, udder volume increased and the fluid in the teats changed from an extracellular-fluid-like to a milk-like composition and acquired a high concentration of immunoglobulins. Four goats accumulated several litres of a pre-colostral fluid with a high [lactose] 6-7 weeks pre-partum. 4. Comparison of the rate of increase in udder volume with previous data for the rate of increase in empty udder volume in pregnant goats showed that the rate of secretion, even in the last few days of pregnancy, was only a few per cent of the rate immediately after parturition. 5. In the last 2-3 days of pregnancy there was a three to elevenfold increase in [citrate] in the secretion; this heralded the onset of copious secretion at about the time of parturition. 6. The changes in mammary gland activities are discussed in relation to changes in plasma hormone concentrations during pregnancy.

Animals↗

Milk secretion in the rabbit: changes during lactation and the mechanism of ion transport.

Changes in the yield and composition of milk and in the permeability of the mammary epithelium to labelled disaccharides and ions have been studied during lactation in rabbits of the Dutch breed. 2. Milk yield increased to reach a peak on day 20 of lactation and then declined, but by 30-32 days the yield was still relatively high. Milk [protein] and [fat] increased in late lactation; [Na] and [Cl] decreased from early to established lactation (11-14 days) and then increased, whereas milk [K] and [lactose] showed an inverse pattern to that displayed by[Na] and [Cl]. 3. At all stages of lactation [Na] and [Cl] were both inversely related to milk [lactose] while [K] showed a positive correlation. 4. Labelled lactose and sucrose were found to cross the mammary epithelium at all stages but in increased amounts during late lactation. Sucrose entry from blood into milk was positively correlated with milk [Na], and inversely correlated with [K] and [lactose]. 5. The entry of (24)Na and (36)Cl into milk from blood paralleled the changes in milk [Na] and [Cl]. 6. Intracellular ionic composition determined in vitro was similar for [Na] and [K] in both established (11-14 days) and late (25-28 days) lactation, but [Cl] was higher in late lactation. 7. Intracellular potentials recorded in vivo were -31 mV (mean) and -36 mV in established and late lactation respectively. Transepithelial p.d. was close to zero at both stages. 8. It is suggested that ions and lactose and other small molecules can cross the mammary epithelium by a paracellular, as well as by a transcellular route, throughout lactation and that the paracellular pathway is increased in late lactation. 9. The site of the proposed paracellular pathway and the implications of such a pathway's presence on ion transport are discussed, and a scheme is suggested to account for the ionic composition of milk in this species.

Animals↗

The effects of prolactin and oxytocin on milk secretion and on the permeability of the mammary epithelium in the rabbit.

The effects of prolactin or oxytocin on milk secretion and the permeability of the mammary epithelium have been investigated in rabbits. 2. Milk yield was increased by prolactin treatment in late (25-28 days) but not in established (11-14 days) lactation. 3. Prolactin treatment increased milk [lactose] and [K] and decreased [Na] and [Cl] in late lactation, and thus reversed the normal changes in late lactation, but had no significant effect in established lactation. 4. [14C]sucrose movements from blood to milk were significantly decreased to levels characteristic of established lactation, following prolactin treatment in late lactation. No significant effect was evident with treatment in established lactation. Na and Cl movements showed similar trends. 5. It is suggested that prolactin in some way affects paracellular movements of ions and small molecules like lactose across the mammary epithelium, and that this mechanism is responsible for the changes in the composition of the aqueous phase of milk. 6. Immediately following a single dose of 100 m-u. oxytocin no significant effects on milk composition were evident but after 1 u. milk [Na] and [cl] were significantly increased. 7. Twenty-four hr after 1 u. oxytocin, milk [Na] and [cl] were decreased while [K], [lactose], [fat] and [protein] were increased. 8. During an I.V. infusion of oxytocin milk [Na] and [Cl] increased while [K] and [lactose] decreased. The passage of [(14)C]sucrose, 24Na and (36)Cl from blood to milk also increased. 9. These effects of oxytocin are discussed in relation to the permeability of the mammary epithelium and the pathways for ion movements, and to other studies on milk composition in the rabbit involving the administration of oxytocin to aid in the evacuation of milk.

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