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Biomedical subjects

C H Knight

Publications and source records attributed to C H Knight.

At least 55 records · Page 3Linked to original sources
PubMed1992

Mammary development and milk secretion in transgenic mice expressing the sheep beta-lactoglobulin gene.

Mammary development and milk secretion were studied in transgenic mice which exhibited mammary tissue-specific expression of the sheep beta-lactoglobulin gene, and secreted significant quantities of the foreign protein in milk. Mammary development was unaffected by transgenesis. Tissue DNA content and the activities of several key enzyme markers of cell differentiation were similar in transgenic mice and non-transgenic controls. Milk yield, whether estimated by pup weight gain or measured by a 3H2O-dilution method, was unchanged by foreign gene expression. Gross milk composition, including milk protein concentration, was also similar in transgenic and non-transgenic animals, even though beta-lactoglobulin accounted for 29% of total milk protein. Therefore the foreign gene product was synthesized at the expense of endogenous milk proteins. However, transgenic mammary tissue in vitro exhibited a significantly higher rate of total protein synthesis than did control tissue. This suggested that a factor limiting milk protein synthesis or secretion in transgenic mice in vivo may have been removed by short-term explant culture of mammary tissue. The results emphasize that the use of transgenesis for manipulating milk composition may depend not only on high-level mammary-specific expression of the foreign gene, but also on the biosynthetic capacity of the mammary gland itself.

Aging↗
PubMed1992

Milk yield responses to sequential treatments with recombinant bovine somatotropin and frequent milking in lactating goats.

Lactating goats routinely milked twice daily were used. Starting at peak lactation, two groups of five goats were milked three times daily unilaterally (right gland) for 6 weeks, then one group received recombinant bovine somatotrophin (BST) by daily injection for 6 weeks, and finally both groups were returned to unilateral thrice-daily milking (left gland) for 6 weeks. Thrice-daily milking increased milk yield significantly by 10.4%. As thrice-daily milking finished and BST treatment began there was a small (2.7%) but significant increase in whole-udder milk yield in the treated goats and a decline in the control goats; throughout the BST treatment period treated goats produced 14.3% more milk than controls. The effect of BST was the same in glands previously milked thrice daily as in those previously milked twice daily. Milk yield declined as BST treatment finished, but this decline was less in the glands that then began thrice-daily milking. The effect of milking frequency was similar in this period to that obtained earlier in the experiment, and was not different between goats that had previously received BST and those that had not. The results are discussed in relation to the proposed modes of action of BST and frequent milking, and possible interactions between the two.

Analysis of Variance↗
PubMed1992

Separate and additive stimulation of bovine milk yield by the local and systemic galactopoietic stimuli of frequent milking and growth hormone.

Lactating heifers were treated for 4 weeks with recombinant bovine growth hormone (bGH, n = 9) or were untreated (n = 9). In addition, two mammary glands of each heifer were milked four times daily rather than the normal twice daily for the same 4 weeks, and for the following 2 weeks. Over the 4 weeks, milk yield was increased 12.8% by bGH, 14.0% by frequent milking and 28.5% by the combined treatment. The effect of bGH as administered here was slower in onset than that of frequency, but eventually produced a higher peak yield. ANOVA revealed significant effects of each stimulus independently and an additive, but not synergic effect of the combined treatment. The effect of the combined treatment tended to persist beyond the end of treatment; most of this response was related to the milking frequency component rather than the bGH. Mammary differentiation was assessed in biopsies of mammary tissue obtained prior to and at the end of treatment. Mammary enzyme activities (expressed on a per cell basis) indicated minimal differentiative response to either treatment, but synthesis rates for lactose and casein determined in vitro were increased by bGH treatment. Histological examination revealed a stimulatory effect of milking frequency on epithelial cell size. The results indicate that these two galactopoietic stimuli operate through independent mechanisms, and neither stimulus alone is sufficient to maximize milk yield in dairy heifers.

Acetyl-CoA Carboxylase↗
PubMed1992

Effect of stage of lactation and milk accumulation on mammary cell differentiation in lactating bats.

Mammary cell differentiation was measured in lactating pipistrelle bats (Pipistrellus pipistrellus) by assay of key enzyme activities, and by determination of protein and lactose synthesis rates in short-term tissue cultures. By these criteria, mammary cell differentiation did not change significantly with stage of lactation, but depended on the extent to which the gland was filled with milk. Key enzyme activities and in vitro synthesis rates were significantly higher in glands suckled immediately before tissue collection, compared with contralateral glands that were engorged with milk. This indicates that mammary cell differentiation in the lactating bat is regulated locally within each gland by a mechanism sensitive to milk accumulation, to the extent that, unlike other species, this obscures any underlying effect of stage of lactation.

Animals↗
PubMed1991

In-vivo magnetic resonance imaging studies of mammogenesis in non-pregnant goats treated with exogenous steroids.

Mammogenesis and lactation were induced in five multiparous, non-pregnant goats by treatment with oestrogen and progesterone for 11 d, followed by dexamethasone for 3 d. Reserpine was administered during the last 5 d. All five goats lactated, although milk yield was less than had been achieved in previous natural lactations. Mammary development was assessed in vivo, using magnetic resonance imaging. Although parenchyma volume increased by more than 6-fold overall, only 25% of this increase occurred during steroid treatment. Most development took place after the cessation of treatment, when milking commenced. Maximum size was not achieved until week 8 of the induced lactation, and was only 70% of normal parenchyma volume. After 18 weeks lactation the activities of three key milk synthetic enzymes were very similar to values previously found in natural lactations, and secretion efficiency (milk production per unit volume of parenchyma) was also similar to that of natural lactations. We conclude that the lower than normal milk yields were associated with incomplete proliferation of mammary tissue, rather than inadequate differentiation of individual secretory cells.

Animals↗
PubMed1991

Omitting the dry period between lactations does not reduce subsequent milk production in goats.

Four goats were studied from the end of their second lactation. One mammary gland of each goat was dried off just prior to the start of the third gestation, whilst the other gland was milked throughout gestation, with no dry period. At the end of gestation the continuously milked gland was significantly smaller than the gland that had been allowed a dry period. However, this difference did not persist beyond parturition and there was no significant difference between the milk yields of the two glands in the next lactation, although the continuously milked gland tended to have the higher yield. At 18 weeks of lactation, mammary parenchyma weight and secretory cell number were significantly greater in the continuously milked gland, but mammary enzyme activities did not differ between the two glands.

Animals↗
PubMed1990

Milk yield and mammary function in dairy cows milked four times daily.

Groups of lactating cows and heifers were milked four times daily in two diagonally opposed glands for 4 weeks, and the effects on milk yield studied relative to twice-daily milked glands as controls. Mammary enzyme activities, in vitro synthesis rates of milk constituents and histological scoring were determined in mammary biopsy samples obtained at the end of this period. These were used for assessment of mammary function. Frequent milking increased milk yield only in the treated glands, the contralateral control glands continuing to decline in yield at approximately 2%/week. There was no significant difference in response between cows and heifers; the mean increase in yield was 10.4%. The rate of decline in milk yield tended to decrease with frequent milking, to approximately 1%/week. Consequently the yield of the treated glands continued to be elevated above that of the controls for some time after reversion to overall twice daily milking. Milk protein content was increased slightly by frequent milking. Mammary enzyme activities were approximately 18% higher in the treated glands than in the controls. Synthesis rates of lactose, casein and total protein were unaffected by milking frequency, but were all lower in the gland selected for the second biopsy, reflecting the reduction in milk yield caused by the first biopsy. DNA synthesis was increased by milking frequency, as were the size and number of epithelial cells in histological sections.

Animals↗
PubMed1990

Milk yield and mammary function in goats during and after once-daily milking.

Starting in week 5 of lactation, goats were milked unilaterally once daily for 4 1/2 weeks, then twice daily for 12 weeks and finally thrice daily for 2 weeks. The control gland was milked twice daily throughout. During less frequent milking, yield fell by 26%. There was a rapid and essentially complete recovery of milk yield on resumption of twice-daily milking, and five of the six goats subsequently responded to thrice-daily milking with a small increase in milk yield. Mammary function was assessed during each phase by determining enzyme activities and in vitro synthesis rates of lactose and casein in mammary biopsies. There was a trend towards reduced differentiation of secretory cells during infrequent milking, with very little recovery during twice-daily milking but complete recovery during thrice-daily milking. The differentiative state of the control gland remained unchanged throughout.

Animals↗
PubMed1990

Cyclic changes in composition and volume of the breast during the menstrual cycle, measured by magnetic resonance imaging.

The volumes and spin-lattice (T1) relaxation times of breast tissues and parenchymal water content were measured non-invasively by magnetic resonance imaging (MRI) in eight healthy women during four to eight consecutive menstrual cycles. Total breast volume, and parenchymal volume, T1 relaxation time and water content were lowest between days 6 and 15. Between days 16 and 28, parenchymal volume, T1 relaxation time and water content rose sharply by 38.9%, 15.1% and 24.5%, respectively, and peaked after day 25. Within 5 days of the onset of menses, parenchymal volume fell sharply by 30.3%, while water content declined by 17.5%. Rising parenchymal volume in the second half of the menstrual cycle is not solely due to increased tissue water content and provides in vivo evidence for both growth and increased tissue fluid at this time.

Adult↗
PubMed1990

Use of magnetic resonance imaging in the study of goat mammary glands in vivo.

A technique is described for the in-vivo determination of mammary gland size and gross composition in goats by using nuclear magnetic resonance imaging (MRI). The volume of test objects determined with MRI had an error of +0.4 +/- 1.6% of the actual volume. In lactating goats the in-vivo MRI estimate of mammary parenchymal volume was significantly greater than, but highly significantly correlated with, the weight of parenchyma determined post mortem (for the whole udder, r = 0.88, P less than 0.001; for individual glands, r = 0.85, P less than 0.001). MRI-determined estimates of the volume of fluid within the mammary gland were within 1.2% of the volume of milk removed from the udders after imaging. The spin-lattice (T1) relaxation time of the whole udder correlated closely with the volume of fluid within the udder. The T1 relaxation time of parenchymal tissue measured in vivo did not differ significantly from that determined immediately after post-mortem excision.

Animals↗
PubMed1990

In-vivo studies of mammary development in the goat using magnetic resonance imaging (MRI).

Mammary development and regression were measured in goats in vivo using magnetic resonance imaging (MRI). Measurements were made during the first and second cycles of pregnancy, lactation and involution. In primiparous goats, and exponential pattern of growth was evident during gestation and for the first 2 weeks of lactation. Parenchyma volume correlated significantly with milk yield across goats during early lactation, and across stage of lactation within goats. Milking was discontinued in Week 26 of the first lactation. Involution was characterized by an initial accumulation of fluid (over 2 days) followed by reabsorption; parenchyma volume did not decrease significantly until the 3rd week of involution, which was also the time at which these goats were mated to start their second gestation. Their udders still contained significant quantities of fluid (40-60% of the gross volume), but parenchyma volume was also greater (by 4.7-fold) than in goats beginning their first gestation. By Week 15 of gestation there was no longer a parity difference in parenchyma; the udders of first-gestation goats had grown significantly, but those of second-gestation goats had not. Conversely, between gestation Week 15 and lactation Week 2 mammary growth was significantly more rapid in the second cycle, such that the udder was larger at the start of the second lactation.

Animals↗
PubMed1990

Galactopoietic and mammogenic effects of long-term treatment with bovine growth hormone and thrice daily milking in goats.

Starting in mid-lactation, goats were treated daily for 22 weeks with 0.15 mg recombinant bovine GH (bGH)/kg, or an equivalent volume of vehicle. One gland of each goat was milked thrice daily throughout treatment, the other twice daily. Mammary differentiation was studied in biopsy samples obtained before treatment and after 3 and 22 weeks of treatment, by determination of in-vitro synthesis rates of milk constituents and measurement of enzyme activities. Mammary growth was measured using a whole-body imaging technique (magnetic resonance imaging; MRI). bGH caused an immediate and sustained increase in milk yield of approximately 23% overall, whilst the glands milked thrice daily produced approximately 14% more than the control glands milked twice daily. The effects of the combined treatment were additive, but not synergistic. A synergistic effect of the combined treatment resulted in a significant improvement in lactation persistency. A stimulatory effect of milking frequency on mammary enzyme activities was evident only in bGH-treated goats at 3 weeks, but in both groups at 22 weeks. Synthesis rates of casein and lactose were increased at 3 weeks only by the combined treatment. Thus bGH accelerated or augmented the differentiative response to thrice daily milking. Mammary parenchyma volume, estimated by MRI, increased significantly during the first 12 weeks of bGH treatment and remained higher throughout the rest of the treatment period. Cell number was estimated from parenchyma volume and DNA concentration; this decreased significantly in the controls between weeks 1 and 22, but remained constant in the bGH group. In nine of the ten goats, parenchyma volume and cell number increased in the gland milked thrice daily relative to the control gland milked twice daily during the course of the experiment. Thus bGH stimulated growth of the mammary gland over and above that induced by the frequent milking. The absence of any detectable increase in thymidine incorporation suggests that this growth consisted of cellular hypertrophy rather than hyperplasia.

Acetyl-CoA Carboxylase↗
PubMed1989

Regulation of intracellular casein degradation by secreted milk proteins.

Intracellular degradation of newly synthesised casein was measured by a pulse-chase method in freshly prepared goat mammary explants. After incubation in medium containing L-[5-3H]proline, explants were washed and cultured again in unlabelled medium containing 5 mM proline; at intervals up to 24 h the amount of radiolabel incorporated in casein was measured. Tissue was obtained in week 33 of lactation after goats had been milked incompletely in one gland (the test gland) for 24 weeks; the contra-lateral (control) gland was milked normally. In explants from the control gland, casein was not degraded during or after secretion: L-[5-3H]proline incorporated in casein increased to a maximum value which was maintained through the chase period. For four out of five goats, explants from the test gland showed a decrease in total [3H]casein radiolabel at 0-4 h of the chase, indicating that a proportion of casein was degraded during secretion. Intracellular casein degradation was also observed when control gland explants were cultured in chase medium containing a goat whey fraction known to inhibit casein production and milk secretion (Wilde, C.J. et al., (1987) Biochem. J. 242, 285-288). This suggests that the greater volume of residual milk left by incomplete milking reduced secretory efficiency, rendering casein susceptible to intracellular degradation, and that this occurred through the action of a secreted milk constituent, which acts as a chemical feedback inhibitor of milk secretion.

Animals↗
PubMed1989

Antibiotic persistence and tolerance in the lactating goat following intramammary therapy.

Due to the impact of the dairy quota system, the commercial use of goats for the production of milk and associated products is attractive to farmers diversifying their dairy interest. Intensification of milking and the expansion of herds will inevitably increase the incidence of caprine mastitis. The pharmaceutical industry and the veterinary surgeon will be required to provide data and advice upon the performance of currently available bovine intramammary products when used in the goat. This study produced evidence that one available bovine intramammary product, when infused into the glands of milking goats, produced a withholding time approximately double that defined for the cow. Following a course of infusions after three successive milkings, milk was not available for human consumption or for the production of cheese and yoghurt until 112 hours after the final infusion. This situation is likely to be representative of that which will occur for other currently available bovine intramammaries when prescribed in the goat.

Amoxicillin↗
PubMed1989

Metabolic adaptations in goat mammary tissue during long-term incomplete milking.

Lactating goats were milked incompletely in one gland and normally in the other gland twice daily for 24 weeks. Yields of the incompletely milked glands were adjusted so that a calculated 100 ml milk remained in the gland at the end of milking. On average this residual volume was greater by 7.6% of the total milk volume than that left after normal milking and was 25.9% greater than the capacity of the alveoli. After 24 weeks, the weekly milk yield of the incompletely milked gland was 23.8% lower than that of the other gland (P less than 0.001) when expressed in relation to cell number. The metabolic capacity of secretory cells in the two glands was measured in serial tissue biopsies. Two weeks of incomplete milking had no effect on enzyme activities or metabolic fluxes in the incompletely milked gland, but after 24 weeks the activities of several key enzymes were significantly lower in this gland. This was associated with a reduced rate of synthesis of total protein and casein in explants freshly prepared from the tissue. The rate of lactose synthesis also tended to be lower in explants from the incompletely milked gland. Secretory cell number in the two glands was similar at the end of incomplete milking. The data indicate that incomplete milking over a long period caused partial secretory cellular involution via a local chemical feedback mechanism in the gland.

Adaptation, Physiological↗
PubMed1989

Metabolic adaptations in mammary gland during the declining phase of lactation.

Peak milk yield in the ruminant animal is attained relatively early during lactation, and this is followed by a progressive decline so that at the time of "drying off" yield may be reduced to only 50% of its maximum value. Studies in lactating goats indicate that the fall in milk yield after peak was due ultimately to a decrease in the number of secretory cells and that the remaining cells did not lose their metabolic capacity for milk synthesis to any significant degree. Manipulation of milking frequency or efficiency during declining lactation had both acute and long-term effects on milk yield and mammary cell number and activity. Rapid and reversible stimulation of yield by thrice daily or hourly milking was due to more frequent removal of a whey protein, which modulates milk secretion by negative chemical feedback on the secretory cell. Evidence is presented that the feedback inhibitor may act primarily on the secretory process rather than through inhibition of synthesis of individual milk constituents. Long-term thrice daily milking increased milk yield in the later stages of lactation by preventing, at least in part, the fall in secretory cell number after peak. Secretory cell differentiation was also susceptible to manipulation in declining lactation: inefficient milking for 24 wk after peak, i.e., by increasing the residual milk volume in the gland after milking, caused partial involution (dedifferentiation) of the existing secretory cell population. The role of local intramammary mechanisms in modulating milk yield and mammary function in declining lactation is discussed.

Animals↗
PubMed1988

Milk production in concurrently pregnant and lactating goats mated out of season.

Five lactating goats which had kidded normally in March were mated during seasonal anoestrus in May, at the time of peak milk production, after ovulation had been induced using gonadotrophin-releasing hormone (Knight et al. 1988). Milk yield was unaffected by the hormone treatment, and decreased at the same rate as that of control (non-pregnant) goats for the first 8 weeks of the pregnancy. Thereafter yield declined more quickly in the test goats and just before parturition (in October) was 57% of the control value. Following parturition in the test animals, yield rose rapidly as the second lactation was established. None became 'dry' at any stage. Yield continued to decline with advancing lactation in the controls, which were mated normally in October or November and dried-off in December. During their second ('extra') lactation in the winter the test animals produced 12% less than in a normal second lactation in summertime; during the year the extra lactation meant that the test animals produced 73% more milk than the controls. In some, a second concurrent pregnancy was established during the extra lactation, with the result that three lactations were obtained in the time normally taken for two. Mammary cell number and proliferation rate were both higher in the pregnant animals than in the controls in week 23 of the first lactation.

Anestrus↗