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Biomedical subjects

C H Knight

Publications and source records attributed to C H Knight.

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

Growth hormone and mammary development.

Classic studies in rodents conducted in the 1950s showed that growth hormone (GH) is essential for mammary development both in the pubertal phase and during pregnancy. Since then, a considerable number of experiments have been carried out in ruminants to investigate the role of GH for regulation of normal mammary development and to examine the possibility of enhancing mammary growth by administration of GH. The available evidence demonstrates that GH treatment stimulates mammary growth before puberty, but the data do not convincingly support the idea that the effect is translated into increased milk yield. GH treatment during late pregnancy seems to stimulate both mammary growth and milk yield during lactation. The limited data concerning the effect of GH on mammary growth during lactation indicate that mammary growth is unaffected by GH treatment in early lactation, whereas GH seems to increase the amount of mammary parenchyma in mid-lactation. The mechanism of action of GH remains a puzzle, but the effect of exogenous GH most likely involves insulin-like growth factor-I (IGF-I). Full understanding of the role of endogenous GH for regulation of normal mammary development requires more knowledge about the interaction between GH and IGF-I and the interplay between the GH-IGF-I axis and locally produced factors, including receptors, binding proteins, and growth factors.

Animals↗
PubMed1999

Effect of endocrine and paracrine factors on protein synthesis and cell proliferation in bovine hoof tissue culture.

Laminitis is a major cause of lameness in dairy cattle, and is widely attributed to a defect in the horny tissue that gives the hoof its mechanical strength. Defective horn is associated with, and may be preceded by, impaired keratin deposition in the hoof epidermis. The cause of abnormal keratin deposition is not easily identified but, like epidermal keratinization in other tissues, is likely to be controlled by hormones and the paracrine action of locally produced growth factors. The hormonal regulation of keratin synthesis and cell proliferation in the bovine hoof was studied using tissue explants in organ culture. As the highest incidence of laminitis is in early lactation, the study focused on insulin, cortisol and prolactin, three hormones implicated in lactogenesis and galactopoiesis. Incubation of tissue explants for 24 h in medium containing insulin (10-5000 ng/ml) stimulated protein synthesis measured by incorporation of 35S-labelled amino acids. Histochemical examination showed that insulin binding co-localized with the site of protein synthesis. Insulin also stimulated DNA synthesis, an index of cell proliferation, which was measured by incorporation of [3H]methyl thymidine. Cortisol (10-5000 ng/ml) decreased protein synthesis, whereas prolactin (10-5000 ng/ml) had no significant effect on protein or DNA synthesis. Epidermal growth factor (10-200 ng/ml), a potent inhibitor of keratinization in other tissues, stimulated protein synthesis compared with untreated controls. Epidermal growth factor binding was located microscopically to the germinal and differentiating epidermal layers. SDS-PAGE and fluorography showed that the population of proteins synthesized in the presence of any hormone or growth factor combination did not differ from that in untreated controls and included the keratins involved in horn deposition. The results show that bovine hoof keratinization is under endocrine and growth factor control, and suggest that systemic changes in lactogenic hormones may act to inhibit keratin deposition.

Animals↗
PubMed1999

Effect of feeding before, during and after milking on milk production and the hormones oxytocin, prolactin, gastrin and somatostatin.

Feeding during milking has been shown to influence milk production, milk flow and milking time as well as the secretion of the pituitary hormones oxytocin and prolactin, and the gastrointestinal hormone somatostatin. However, it is not known whether feeding before or after milking has any effect. The aim of the present study was to investigate how the timing of feeding relative to milking influences milk production and flow, milking time and hormone secretion. The trial was carried out over 9 weeks with 24 cows at varying stages of lactation. Each treatment period lasted for 3 weeks, including one registration week. The cows were fed ad lib. and were exposed to three treatments: feeding 1.5 h before milking (FBM), feeding at exactly the same time as milking (FDM) and feeding 1.5 h after milking (FAM). The most marked treatment effect was observed during morning milking. FDM resulted in higher milk production and higher yields of protein and lactose. FAM produced a lower fat yield and a lower fat content compared with FDM, and a lower lactose content than either FBM and FDM. Milking time was longer when cows were fed during milking, but no significant effects on milk flow were found. The amount of milk collected during the first 2 min of milking was lower when cows were fed after milking. Milking-related oxytocin and somatostatin secretion was lower in FAM than in FDM. The level of prolactin was lower when cows were fed before or after than during milking. More studies are needed to elucidate whether there is a long-term effect on milk production related to the discussed milking routines.

Animals↗
PubMed1999

Control of milk secretion and apoptosis during mammary involution.

Lactation depends on regular suckling or milking of the mammary gland. Without this stimulus, milk secretion stops and mammary involution is induced. Involution caused by abrupt cessation of milk removal is characterized by de-differentiation and apoptosis of mammary epithelial cells, the extent and time course of the latter varying between species. Apoptosis is inhibited and milk secretion is restored by re-suckling, if milk stasis is of short duration. Mammary involution and apoptosis also occur during weaning, even in concurrently-pregnant animals when the interval between lactations is restricted, suggesting that tissue remodeling is essential for subsequent lactation. Declining milk production in ruminants after peak lactation is also associated with, and probably results from, net cell loss by apoptosis. Involution and apoptosis are controlled by changes in systemic galactopoietic hormone levels, and by intra-mammary mechanisms responsive to milk removal. Milk stasis precipitated by litter removal or cessation of milking may involve intra-mammary control related to physical distension of the epithelium. Local control of apoptosis in rodents during weaning, and after peak lactation in dairy animals, may be due to the actions of milk-borne survival factors or their inhibitors, and can be manipulated by frequency of milk removal.

Animals↗
PubMed1998

Partitioning of milk accumulation between cisternal and alveolar compartments of the bovine udder: relationship to production loss during once daily milking.

Experiments were undertaken to validate a method (using adrenaline injection) for determination of the size of cisternal and alveolar compartments in the udder, to use this method to determine the pattern of milk accumulation in the udder over time and to determine the relationship between the size of the alveolar and cisternal compartments and tolerance of once daily milking. Cows received intrajugular injections of adrenaline (3 mg) immediately before milking, to block milk ejection and allow harvesting of the cisternal milk fraction. This was followed by removal of the alveolar fraction 30 min later after intrajugular oxytocin (5 i.u.) injection. Results obtained were similar to those obtained by catheter drainage. The alveolar compartment was 90% full at 16 h post milking while the cisternal compartment filled more slowly and was only 70% full at 24 h post milking. At full capacity (measured at 40 h), the volumes of milk contained in the cisternal and alveolar compartments were similar. In a further experiment involving identical twin cows, it was shown that the greater the degree of filling of the cisternal compartment at 24 h, the lower was the production loss on once daily milking. This suggests that the freedom of the alveoli to drain was an important factor in the production loss on once daily milking. Although there were significant correlations within twin sets for milk yield and the size of udder compartments, the relationship within twin sets for yield loss on once daily milking was not statistically significant.

Animals↗
PubMed1998

Local control of mammary development and function.

For the mother, lactation represents the final stage of an investment in her genetic material. Like any investment it is costly and, hence, it needs to be carefully controlled. To her offspring, lactation means survival, so it must happen at any cost. This apparent conflict is rationalized by the mother devolving some control to the offspring while retaining ultimate sanction herself. Part of this results from overt and more subtle influences of the presence of young on the mother's endocrine system, but an equally important part operates at each mammary gland to ensure that output is appropriate to the needs of the young, and no more. The young exert influence by removing milk, while the mother retains control by responding on an hour to hour basis to the presence of milk in the gland. Local control is inevitably most evident where secretion itself is concerned, but also operates to influence lactogenesis, gland development and, eventually, gland involution. This paper will review local control of mammary function, emphasising the important role played by an autocrine inhibitory protein, the feedback inhibitor of lactation.

Animals↗
PubMed1998

Local control of the mammary gland.

Studies on increasing the frequency of milking in dairy animals have led to the uncovering of the mechanism by which tactical control of the rate of milk secretion is achieved locally within each mammary gland, against a strategic, systemic control by the hormones that maintain all glands in the secretory condition. Experiments in vivo established that the response is local, and were compatible with the hypothesis that milk contains an inhibitor of its own secretion which accumulates during storage within the lumen of the mammary gland and which acts in an autocrine manner on the secretory cells. Isolation of a protein, initially from goats' milk, called FIL (feedback inhibitor of lactation) has enabled, and is enabling, further studies to be done from the whole-animal down to the molecular level. Examples at the whole-animal level are: the effects of immunization against FIL on the rate of secretion; the concentration of FIL and the kinetics of its formation and breakdown; the importance of the internal structure of the mammary gland and the capacities of the alveolar and ductular storage regions in determining feedback inhibition; differences between individuals and species influencing the degree of control exerted by FIL in matching supply of milk to demand by the young. Other local control mechanisms at the onset and cessation of lactation, including mammary distension, are also discussed.

Animals↗
PubMed1998

Autocrine regulation of milk secretion.

Mammary development and the rate of milk secretion are regulated by frequency and completeness of milk removal. This regulation occurs through chemical feedback inhibition by a milk constituent. Novel, immunologically related milk proteins able to perform this function have been isolated from caprine, bovine and human milk, based on their ability to inhibit milk constituent synthesis in mammary tissue and cell cultures, and to decrease temporarily milk secretion when added to milk stored in the mammary gland. Inhibition is concentration-dependent, suggesting that milk accumulation and removal is accompanied by cyclical changes in inhibitor accretion and depletion in milk. Feedback inhibition is an autocrine mechanism: the caprine inhibitor, termed FIL (feedback inhibitor of lactation) is synthesized by mammary epithelial cells in primary culture. Inhibition is by reversible blockade of the secretory pathway, an effect which, by down-regulating cell-surface hormone receptors, has longer-term consequences on epithelial cell differentiation. Treatment of goat mammary epithelial cell cultures with caprine FIL initially decreased milk protein secretion and subsequently reduced milk protein messenger RNA abundance. Thus the actions of a single milk constituent can bring about both the effect of milking frequency on milk secretion rate and a sequential modulation of cellular differentiation which acts to sustain the secretory response. Long-term regulation, through changes in galactopoietic hormone receptors, also provides an efficient mechanism for integrating acute intramammary regulation of lactation with strategic endocrine control of mammary tissue development.

Animals↗
PubMed1997

Effect of unilateral once or twice daily milking of cows on milk yield and udder characteristics in early and late lactation.

Twelve multiparous British Friesian cows in early (40 +/- 23 d in milk; n = 6) or late (216 +/- 17 d in milk; n = 6) lactation were used to study the effects of milking frequency on yield, udder volume and milk storage within the udder. After a 2 week control period of twice daily milking, diagonally opposed udder halves within a cow were milked once or twice daily for 3 weeks. Milk yield was 28-38% lower from the halves that were milked once daily than from halves that were milked twice daily. The loss of milk yield, expressed as a decrease in the relative milk yield quotient (an index that accounts for pretreatment differences), was greater for cows in early than in late lactation (0.59 v. 0.68). Empty udder-half volume was not decreased by once daily milking, suggesting that no cell loss occurred. Instead, once daily milking reduced the secretion efficiency (units of milk per unit of empty udder-half volume) by 46 and 27% respectively in early and late lactation; thus, at least part of the loss was due to reduced metabolic activity of the mammary epithelium. There were positive correlations between the relative milk yield quotient and the proportion (r = 0.804) or volume (r = 0.644) of cisternal milk in the glands that were milked once daily. These results confirm that, during extended milking intervals, milk loss was smallest for cows that stored a larger proportion of milk in the gland cistern.

Animals↗
PubMed1997

Interactions of prolactin and growth hormone (GH) in the regulation of mammary gland function and epithelial cell survival.

The relative importance of GH and prolactin in mammary gland function varies between species with prolactin playing a major role in rodents and GH taking lead role in ruminants. In rodents, however, GH appears to play a vital role in maintaining a high-fat/low volume milk in the absence of prolactin and a similar finding has been demonstrated in goats where prolactin deficiency causes a more modest (15%) decrease in milk yield. Surprisingly GH-deficiency in goats induced no further decline in milk yield whereas exogenous GH or prolactin both stimulated milk output considerably. Although direct effects of prolactin on mammary epithelial cells are well-documented effects of GH are believed to be mediated indirectly via IGF-1 production from the liver. We have been unable to confirm this hypothesis in rats and believe this to be because it is too simplistic. By considering prolactin and GH to be survival factors for the mammary gland we now propose a mechanism by which they interact through the IGF system. Involution of the mammary gland involves apoptosis and, in rats, it is induced by prolactin-deficiency or milk accumulation. Coincidentally with this process mammary epithelial cells synthesize and secrete and IGF binding protein, IGFBP-5. We hypothesize that GH stimulates IGF-1 production, possibly from the mammary parenchyma. IGF-1 then acts as a survival factor for the mammary gland. Prolactin plays an essential role since it suppresses the secretion of IGFBP-5 which would otherwise inhibit IGF-1 action and lead to the induction of cell death.

Animals↗
PubMed1996

Continuous versus single drainage of milk from the bovine mammary gland during a 24 hour period.

Five primiparous and five multiparous cows were used to determine if mammary cisternal storage of milk during a 24 h period of milk accumulation limited milk secretion. In addition, we investigated if there is a parity effect for the capacity of the mammary cisternal compartment to hold a 24 h accumulation of milk secretion, and studied the movement of milk from the alveolar compartment into the cisternal compartment. All cows were fitted with catheters in all teats in order to collect cisternal and alveolar milk fractions separately. For a 24 h period of milk accumulation, the milk was drained once (after 24 h) from one side of the udder (OD), and continuously from the other side of the udder (CD). There was no significant parity effect for cisternal, alveolar and total milk volumes at 24 h. Therefore, data from primi- and multiparous cows were pooled for subsequent analyses. Cisternal milk volume from CD glands was higher than that from OD glands (P < 0.01), indicating that cisternal storage of milk in the mammary gland may be limiting to milk secretion during 24 h milking intervals. Alveolar volumes did not differ between OD and CD, but, as a result of the higher cisternal milk volume, total milk volume was highest in the CD glands (P = 0.05). Movement of milk from the alveolar into the cisternal compartment was intermittent. Moreover, analyses of the slopes of individual milk accumulation profiles of the first 6 h of accumulation revealed that the cisternal compartment starts filling immediately following milking, although the rate of filling is relatively low until 7-8 h postmilking.

Animals↗
PubMed1995

Protein synthesis in tissues cultured from the bovine hoof.

The mechanical strength of the bovine hoof depends on keratinization of cells in the germinal layers of the epidermis. Histological examination of hoof tissues in calves and young heifers has identified disturbances in this keratinization process which would result in ineffective hoof development and could precipitate lameness. Short-term culture of bovine hoof tissue was used to investigate epidermal keratinization. Cell function remains viable in these cultures. The rate of protein synthesis, measured by [35S]-methionine incorporation, continued for at least 3 h in culture. Radiolabelled proteins in tissue homogenates were separated by SDS-polyacrylamide gel electrophoresis and characterised by fluorography and were representative of the proteins found in hoof tissue. Three prominent radiolabelled bands were identified as keratins and actin by Western blotting. Immunohistochemistry showed that keratin was localised principally in the epidermal layers, and microautoradiography indicated that this was the major site of protein synthesis. Hoof tissues cultured under these conditions provide a useful system for studying the acute regulation of epidermal keratinization.

Actins↗
PubMed1995

Changes in casein composition of goats' milk during the course of lactation: physiological inferences and technological implications.

Five British Saanen goats were milk sampled during the first 39 weeks of lactation to determine changes in casein composition. Caseins were separated by anion- and cation-exchange FPLC to determine the relative amounts of the individual caseins. Acid, alkaline and SDS-PAGE were used to determine possible genetic polymorphisms and observe any lactational changes. Total casein nitrogen was determined using a micro-Kjeldahl method and this allowed the concentrations of individual caseins to be calculated. The milk of one animal, which had the deduced genotype alpha s1-CnAB, showed higher concentrations of both total and alpha s1-casein. The remainder of the group were either heterozygous alpha s1-CnBE or, more probably, homozygous alpha s1-CnE and produced milk of a generally lower protein concentration. Both FPLC and PAGE results showed that the relative amounts and concentrations of alpha s2-casein decreased with stage of lactation, consistent with its susceptibility to proteolysis. The relative amounts of the breakdown products of plasmin attack on beta-casein, gamma-caseins, were highly negatively correlated with milk yield (r = -0.942, P < 0.001) in the declining phase of lactation, reflecting the gradual involution of the gland at this time. The relative amount of kappa-casein increased by approximately 50% after peak lactation and its concentration almost doubled near the end of lactation. These compositional changes may alter the processing qualities of goats' milk in relation to cheese production.

Animals↗
PubMed1995

Relationship between frequent milking or suckling in early lactation and milk production of high producing dairy cows.

Groups of 9 or 10 cows were assigned to one of three treatments 1) machine-milking three times daily, 2) machine-milking six times daily, and 3) suckling three times daily in addition to machine- milking three times daily. Treatments were conducted during the first 6 wk postpartum; thereafter, all cows were milked three times daily. During treatment, milk production was highest for suckled cows and lowest for cows milked three times daily. The DMI were similar for suckled cows and cows milked three times daily but higher for those milked six times daily. Body weight loss was greatest for suckled cows and least for cows milked three times daily. During wk 7 to 18 postpartum, cows milked six times daily exhibited a carry-over effect on milk production that was greater than that of other groups, During treatment, plasma growth hormone and IGF-I concentrations were elevated for suckled cows and, to a lesser extent, for cows milked six times daily. Prolactin and oxytocin similarly increased, but insulin decreased in suckled cows and, to a lesser extent, in cows milked six times daily. Posttreatment differences persisted for insulin and IGF-I, but not for the other hormones. Increased frequency of udder emptying increased milk production, and suckling was superior to machine-milking. High milk production was associated with elevated growth hormone, IGF-I, prolactin, and oxytocin, although cause and effect could not be established. The failure of suckled cows to increase feed intake to match output requires further investigation.

Animals↗
PubMed1994

Milk accumulation and distribution in the bovine udder during the interval between milkings.

The proportions of milk stored within the gland cistern (cisternal milk) and within secretory alveolar tissue (alveolar milk) were determined at various intervals after milking in peak lactation cows and late lactation cows. The rate of milk secretion remained constant up to 12 h in both groups. Cisternal milk remained low (600 g or less) until after 4 h in both groups, then increased gradually to values at 12 h of 5.08 (peak lactation) and 2.60 kg (late lactation). Alveolar milk exceeded cisternal milk in both groups and at all time points up to 12 h, and was greatest in the peak lactation cows. A further measurement was made at 20 h in the late lactation group. Milk secretion rate remained constant between 12 and 20 h and most of this additional milk accumulated in the cistern. Alveolar fraction, defined as alveolar milk as a proportion of total milk, ranged from 0.43 to 0.94 at 8 h. There was a highly significant correlation between 8 h and 20 h alveolar milk fraction results, but not between 1 h and 8 h values, nor between alveolar milk at 0 h (effectively residual milk) and alveolar fraction at any time point. The milk volume results were used to construct a mathematical model describing milk flow between cisternal and alveolar compartments, and hence the pattern of milk accumulation. The results are discussed in relation to current hypotheses regarding local autocrine control of milk secretion by a feedback inhibitor in milk.

Animals↗
PubMed1994

Once daily milking of dairy cows: relationship between yield loss and cisternal milk storage.

The proportions of milk stored in the gland cistern (cisternal) and within secretory alveolar tissue (alveolar) were determined for a group of ten cows in mid lactation, yielding approximately 20 kg milk/d. As a proportion of total milk, cisternal milk, measured at 8 h after milking, ranged from 0.09 to 0.53. Milking frequency was then reduced from twice daily to once daily on two occasions, first for 1 week and then, 2 weeks later, for 2 weeks. Milk yield was reduced during once daily milking in all cows, by an average of 22.8% during the first week (P < 0.001). The amount of decrease varied among cows in a way that was unrelated to pretreatment yield, but the immediate decrease was significantly and inversely correlated with cisternal milk proportion (r = 0.81, P < 0.01). When milking reverted to twice daily, yield recovered to a value not significantly different from pretreatment, and the degree of recovery was inversely related to cisternal milk proportion (r = 0.74, P < 0.01). With the exception of one cow, yield decreases correlated well between the two periods of once daily milking. When treatment weeks were disregarded, lactation persistency (the rate of decline in yield with time) was unaffected by once daily milking. The results show that the ability of individual cows to tolerate once daily milking is related to their cisternal storage characteristics; yield is reduced less in cows that store a greater proportion of their total milk production within the cistern.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Short-term oxytocin treatment increases bovine milk yield by enhancing milk removal without any direct action on mammary metabolism.

The milk yield-enhancing effect of oxytocin administered either before or after milking was examined using a within-animal model. Eight cows in mid-lactation were changed from normal twice daily milking to a split-milking design, whereby half of the udder was milked at 0500 and 1500 h (control half; normal milking times), and the other half at 0800 and 1800 h (test half). This continued for 3 weeks. During the second week, oxytocin was administered as an i.m. injection immediately before the 0800 and 1800 h milkings. The test half was thus milked immediately after oxytocin administration, whilst the control half was milked 3 h before oxytocin. Milk yield decreased slightly on the adoption of split-milking. The decrease did not differ between udder halves and was not, therefore, due to inadequate milk-ejection in the test half compared with the control. During the week of oxytocin treatment, the yield decreased further in the control half but increased in the test half; consequently, the yield from the test half was significantly greater than that from the control half (P < 0.05). The ratio of change in the test half relative to that in the control half was 1.12, significantly different from unity (P = 0.002). Analysis of variance demonstrated a significant (P < 0.001) interaction between udder half and oxytocin treatment, confirming that the effect of oxytocin was restricted to the test half, treated immediately before milking. This supports the established view that oxytocin acts by enhancing the milk-ejection reflex, and refutes a recent claim that the hormone has a direct stimulatory action on mammary metabolism.

Analysis of Variance↗