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Biomedical subjects

S R Davis

Publications and source records attributed to S R Davis.

At least 73 records · Page 4Linked to original sources
PubMed1996

Premature ovarian failure.

Premature ovarian failure (POF) is common, affecting approximately 1% of women. It is defined as gonadal failure before the age of 40 and patients may clinically present with either primary or secondary amenorrhoea. This review concentrates on the clinical aspects of POF, with sequential discussion on the aetiology and epidemiology, clinical manifestations and relevant investigations, concluding with an overview of management. In addition, the scientific basis for our current understanding of POF is summarized to provide a comprehensive overview of the diverse pathophysiological mechanisms that may underlie this disorder. Despite the heterogeneity of causes of POF, the fundamental treatment principles are the same. In this review the initiation of hormone replacement therapy in the younger woman and the importance of long term follow-up and treatment are emphasized.

Adult↗
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↗
PubMed1996

An improved method for the routine biopsy of bovine mammary tissue.

Eight primiparous cows in midlactation were used to determine a method for the mammary biopsy of standing cows in full lactation. Cows were mildly sedated; therefore, preoperative feed withdrawal was not necessary. A core of secretory tissue (0.75 to 1 g) was extracted using a rotating stainless steel cannula with a retractable blade at the cutting edge. Postoperative recovery was rapid, taking only 15 min per cow, and the method was reliable and efficient. The presence of secretory tissue was verified by histology and in situ hybridization with alpha s1-casein and alpha-lactalbumin probes. The capsular end of the core contained more connective tissue, and the parenchyma showed heterogeneous expression of alpha s1-casein and alpha-lactalbumin. Despite some postoperative bleeding, milk yield and composition in the biopsied gland were affected only transiently. Yield recovered by 3.5 d after biopsy, and composition recovered by 6.5 d after biopsy. Yield and composition of milk from the control glands were not affected by the procedure. Biopsy sites healed rapidly and without infection. No clinical mastitis was observed in any of the biopsied cows throughout the remainder of the lactation.

Animals↗
PubMed1996

Regulation of blood flow in the mammary microvasculature.

Although milk yield of cows and goats is known to be closely related to the total flow of blood through the udder, a number of studies suggest that milk yield can vary independently. No studies have attempted to measure the proportion of total flow that is nutritive. Within the mammary gland, capillary networks form a basket-like architecture surrounding each alveolus. Notably, flow in individual capillaries is not constant and varies among capillaries. Capillary flow (measured by intravital microscopy) was decreased by oxytocin, which generally increased total flow in the mammary artery, suggesting that the proportion of total flow that is nutritive can vary. In addition to classic metabolic regulators (e.g., carbon dioxide and oxygen) of tissue blood flow, the mammary gland produces a number of vasodilatory compounds, including parathyroid hormone-related protein, insulin-like growth factor-I, prostacyclin, nitric oxide, and endothelin. All of these compounds have been shown to alter mammary blood flow. Mammary tissue also contains kallikrein and angiotensin-converting enzyme, which convert circulating kinins and angiotensin, respectively, into potent vasoactive compounds. A number of these compounds are produced by epithelial cells themselves, providing a mechanism for the functioning epithelium to control its own blood supply and, hence, nutrient flow for milk synthesis. In this review, we examine the nature of the mammary microcirculation, its behavior under different conditions, and some of the regulatory features of the mammary microvasculature.

Animals↗
PubMed1996

Elevation of lactoferrin gene expression in developing, ductal, resting, and regressing parenchymal epithelium of the ruminant mammary gland.

Accumulation of lactoferrin mRNA in mammary tissue from virgin, pregnant, lactating, and involuting ewes and cows was localized using 35S-labeled cRNA probes. Expression of lactoferrin was low in the glands of virgin animals. In the glands of animals in early pregnancy, very high expression occurred in the ducts and immature alveoli, but expression tended to decrease as the alveoli matured. In the lactating and involuting gland, expression was generally low or absent in actively secreting alveoli and high in alveoli that had an accumulation of vesicles in the lumen and secretory epithelium, which was indicative of stasis. Occasionally, expression of lactoferrin was seen in cells that appeared to be secretory, particularly in involuting glands. Lactoferrin mRNA was expressed not only at different sites from other milk protein genes, such as alpha-lactalbumin and alpha s1-casein, but also during different stages of mammary development, supporting the view that the expression of lactoferrin is regulated differently from that of other milk proteins. For all ewes and cows, lactoferrin mRNA was detected in the epithelial ducts of the mammary parenchyma and the teat in a gradient that increased in ducts nearer the teats. The expression of lactoferrin in the ductal epithelium close to the teat was consistent with the antibacterial role of lactoferrin.

Animals↗
PubMed1996

Local secretion of nitric oxide and the control of mammary blood flow.

Our objective was to test the hypothesis that local production of the vasorelaxant nitric oxide could regulate mammary blood flow. In four lactating Saanen goats, the response of mammary blood flow to intraarterial infusion of the nitric oxide donor diethylamine NONOate and the inhibitor of nitric oxide synthesis N omega-nitro-arginine was measured. Diethylamine NONOate induced a rapid and sustained increase of mammary blood flow in the infused gland only, suggesting a direct effect on vasculature of the mammary gland. In contrast, infusion of N omega-nitro-arginine decreased mammary blood flow by up to 35%, and the coinfusion of arginine, the nitric oxide precursor, with N omega-nitro-arginine markedly reduced its ability to decrease mammary blood flow. The distribution of nitric oxide synthase was investigated in cryosections of caprine and bovine mammary tissue by histochemical staining for NADPH-diaphorase activity and by immunocytochemistry using specific antibodies against two nitric oxide synthase isoforms. Both techniques revealed nitric oxide synthase in the vascular endothelium and secretory epithelium of the two species. Only antibodies against nitric oxide synthase-III showed specific staining. These results suggest that the mammary gland produces and responds to nitric oxide and, further, raise the possibility that the epithelium may control its own blood supply by secreting nitric oxide.

Animals↗
PubMed1995

Milk protein synthesis, gene expression, and hormonal responsiveness in primary cultures of mammary cells from lactating sheep.

A ruminant mammary cell culture that accurately reproduces mammary function in vitro would be a valuable tool in studies of ruminant lactation. With this in mind, we have examined milk protein synthesis and secretion, milk protein mRNA abundance, and hormonal responsiveness in primary cultures of mammary acini from lactating sheep. alpha- and beta-casein protein synthesis, beta-lactoglobulin synthesis, and alpha-casein, beta-casein, and beta-lactoglobulin secretion are maintained at high levels for 8 h in culture, but then decline to approximately 25% of maximal rates between 8 and 24 h in culture, whereas synthesis of other proteins remains unaltered. The relative abundance of alpha-S1-casein, beta-lactoglobulin, and alpha-lactalbumin mRNAs similarly decline between 8 and 24 h in culture. Extracellular labeled alpha-casein is increased fourfold in the presence of fetal calf serum (FCS). In total, FCS alters the abundance of 47 of 68 secreted proteins detected by two-dimensional electrophoresis. However, FCS and lactogenic/galactopoietic hormones had no effect on the rate of decline of mammary function and did not promote any regaining of function when present for up to 9 days in culture. These results suggest that providing its limitations are recognized, this primary cell culture system may be useful in studying some aspects of ruminant mammary function in vitro.

Animals↗
PubMed1995

Testosterone enhances estradiol's effects on postmenopausal bone density and sexuality.

To investigate the role of androgens in increasing bone density and improving low libido in postmenopausal women, we have studied the long-term effects of estradiol and testosterone implants on bone mineral density and sexuality in a prospective, 2 year, single-blind randomised trial. Thirty-four postmenopausal volunteers were randomised to treatment with either estradiol implants 50 mg alone (E) or estradiol 50 mg plus testosterone 50 mg (E&T), administered 3-monthly for 2 years. Cyclical oral progestins were taken by those women with an intact uterus. Thirty-two women completed the study. BMD (DEXA) of total body, lumbar vertebrae (L1-L4) and hip area increased significantly in both treatment groups. BMD increased more rapidly in the testosterone treated group at all sites. A substantially greater increase in BMD occurred in the E&T group for total body (P < 0.008), vertebral L1-L4 (P < 0.001) and trochanteric (P < 0.005) measurements. All sexual parameters (Sabbatsberg sexual self-rating scale) improved significantly in both groups. Addition of testosterone resulted in a significantly greater improvement compared to E for sexual activity (P < 0.03), satisfaction (P < 0.03), pleasure (P < 0.01), orgasm (P < 0.035) and relevancy (P < 0.05). Total cholesterol and LDL-cholesterol fell in both groups as did total body fat. Total body fat-free mass (DEXA, anthropometry, impedance) increased in the E&T group only. We concluded that in postmenopausal women, treatment with combined estradiol and testosterone implants was more effective in increasing bone mineral density in the hip and lumbar spine than estradiol implants alone. Significantly greater improvement in sexuality was observed with combined therapy, verifying the therapeutic value of testosterone implants for diminished libido in postmenopausal women. The favourable estrogenic effects on lipids were preserved in women treated with T, in association with beneficial changes in body composition.

Bone Density↗
PubMed1995

EGTA-induced disruption of epithelial cell tight junctions in the lactating caprine mammary gland.

The suitability of the Ca2+ chelator ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) to induce disruption of mammary tight junctions (TJ) and its effect on milk secretion were investigated in six goats. EGTA was administered via the teat of one gland as an isosmotic (300 mosmol/l) K-EGTA solution (68 mM EGTA), whereas the control gland received an isosmotic sucrose solution. Lactose, Na, K, and Cl in milk, blood lactose, and the presence of Evans blue (EB) in mammary lymph were used as indicators of TJ disruption. EGTA caused transient (approximately 60 h) changes (P < 0.05) in the concentration of lactose, K, Na, and Cl in milk, consistent with loss of TJ integrity. This was confirmed by a rapid (< 1 h) increase (P < 0.05) in blood lactose levels. Moreover, EB appeared in lymph < 1 h after EGTA+EB treatment. Milk secretion declined unilaterally by 15% (P < 0.05) after EGTA and did not return to baseline until approximately 60 h after EGTA. EGTA caused a unilateral, temporary (first 7 h) increase in mammary blood flow. This study shows that a rapid temporary disruption of mammary TJ can be successfully induced in vivo and that such disruption compromises milk secretion.

Animals↗
PubMed1995

Pharmacokinetics and bioactivity of intact versus truncated IGF-I during a 24-h infusion into lactating goats.

The aim of this study was to compare the plasma concentration profile, mammary blood flow response and transfer into milk of intact IGF-I with that of its truncated analogue, des(1-3)IGF-I (des-IGF-I). Each peptide was infused for 24 h into the pudic artery supplying one mammary gland of lactating goats (n = 5). Concentrations of IGF-I in plasma (from the jugular vein) rose rapidly during infusion of IGF-I or des-IGF-I to reach 510 +/- 62 and 640 +/- 32 ng/ml (mean +/- S.E.M.) respectively, compared with 262 +/- 35 ng/ml after a similar infusion of saline. Ligand blotting analysis indicated a significant increase in the intensity of [125I]IGF-I binding to the 40-43 kDa doublet (binding protein-3 (BP-3), P < 0.01) and the band at 31 kDa (P < 0.05) during infusion of either IGF-I or des-IGF-I, as compared with saline. Furthermore des-IGF-I induced a significant increase in intensity of binding to the 35 and 24 kDa bands, but IGF-I did not. Whereas [125I]IGF-I was distributed between BP-3 and the other binding proteins, [125I]des-IGF-I bound exclusively to BP-3. Mammary blood flow (MBF) increased 48 +/- 6% after 12 h of infusion of des-IGF-I, compared with an increase of 22 +/- 6% during IGF-I. The difference in response was significant at P < 0.05. In addition, more IGF-I was secreted into the milk of the infused than the non-infused gland during either infusion of IGF-I or des-IGF-I.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Expression of the butyrophilin gene, a milk fat globule membrane protein, is associated with the expression of the alpha S1casein gene.

Previous in situ hybridization studies from our laboratory have shown that expression of certain milk protein genes, e.g. alpha-lactalbumin, is very high in most parts of the mammary glands of sheep and cattle, while in other areas containing an abundance of fat globules it is virtually zero (Molenaar et al., 1992). One possible explanation is that some areas of the mammary gland are dedicated to protein synthesis and some to fat synthesis. To check this possibility, the cRNA for butyrophilin, a milk-fat globule membrane protein, and hence a putative marker of milk fat synthesis, was used as a probe in in situ hybridization studies. The results show quite clearly that the patterns of expression for this gene are similar, cell type for cell type, as those for milk protein genes such as alpha-lactalbumin and alpha S1casein. In addition, we found that butyrophilin gene expression more closely matches that of alpha S1casein than that of alpha-lactalbumin. If it is shown in the future that butyrophilin is indeed a marker for milk fat synthesis, then these results support the current assumption that fat and protein synthesis do occur in the same cell.

Animals↗
PubMed1994

Radiotherapy in the treatment of malignant mesothelioma of the pleura, with special reference to its use in palliation.

Most patients presenting with malignant mesothelioma of the pleura (MMP) are only suitable for palliative treatment. Radiotherapy has not been shown to improve survival in patients with this disease, but is of use in the palliation of symptoms. In this retrospective review of 111 patients with MMP referred to the Peter MacCallum Cancer Institute, the palliative effect of radiotherapy was analysed. More than half of the patients whose response could be assessed had some symptomatic relief from the radiotherapy treatment. No dose-response relationship could be found.

Adult↗
PubMed1994

Increased mammary blood flow in the lactating goat induced by parathyroid hormone-related protein.

Human synthetic parathyroid hormone-related protein (PTHrP) increased mammary blood flow (MBF) following close-arterial infusion via the external pudic artery in goats during mid-lactation. MBF increased 74 +/- 8% within 30 min of the start of continuous infusion of PTHrP compared with 10 +/- 3% in controls. MBF decreased by 90 min, however, and was not different from control values for the remainder of the infusion. The increase in plasma concentrations of calcium and decrease in phosphate during PTHrP suggests that this was not due to altered activity of PTHrP, but may relate to downregulation of response or production of counter-regulatory vasoconstrictive agents within the gland. This problem was alleviated when PTHrP was infused in a pulsatile fashion. An average 14-40% increase in MBF was achieved over 6 h, but this did not alter the rate of milk secretion, suggesting that mammary hyperaemia is not sufficient by itself to increase milk yield in the normally lactating goat. MBF increased in a dose-dependent fashion, although the lowest dose used to give a detectable response was approximately 40-fold higher than the concentration normally present in the mammary venous circulation. Thus, endogenous PTHrP may not be an important regulator of MBF during lactation in the goat.

Animals↗
PubMed1994

Effects of close-arterial (external pudic) infusion of insulin-like growth factor-II on milk yield and mammary blood flow in lactating goats.

Five lactating goats were infused, via an external pudic arterial catheter, directly into the mammary gland with 0.9% (w/v) NaCl (20 ml/h), recombinant human insulin-like growth factor-I (IGF-I; 80 nmol/h), recombinant human IGF-II (133 nmol/h) or IGF-I and IGF-II combined. The infusion was for 6 h and milk yield was determined every 2 h. The ratio of milk yield in the infused relative to the non-infused gland was changed only slightly by saline (2%), but increased to 9% (P < 0.05) in response to IGF-I and 8% (P < 0.05) in response to IGF-II. When combined, both peptides increased this ratio by 6%. These effects were elicited within 2-4 h of the beginning of infusion. Mammary blood flow increased 50-80% (P < 0.05) during all IGF infusions, but only 28% during saline treatment. Plasma insulin decreased 50% (P < 0.01) during the infusion of IGF-I alone or in combination with IGF-II and 25% in response to IGF-II alone. Whereas plasma glucose increased by approximately 10% during infusion of IGF-I alone or with IGF-II, it was not altered by infusion of IGF-II only. The rapidity and unilateral nature of the milk-yield response to IGF-I and IGF-II is consistent with their acting directly on mammary tissue itself. Thus, the present results demonstrate similar local and systemic actions induced by intramammary infusion of IGF-II and IGF-I, although the magnitude of the response to IGF-II tends to be less than that to IGF-I.

Animals↗
PubMed1994

Mammary epithelial cell tight junction integrity and mammary blood flow during an extended milking interval in goats.

The timing and relation of changes in mammary epithelial cell tight junction integrity and mammary blood flow during a 36-h milking interval were studied in six lactating Saanen goats. An increase in lactose concentration in plasma, a decrease in transepithelial potential difference, and changes in ionic milk composition were used to indicate tight junction patency. After 36 h of milk accumulation, mammary tight junctions had become disrupted. Further analyses indicated that this disruption began after 21 h of milk accumulation and that mammary blood flow also started to decline after 21 h. The time when both events occurred was not significantly different from the time when milk secretion began to decline (19 h). Moreover, positive but nonsignificant correlations existed between these events. Mammary tight junctions became disrupted when milk secretion declined, suggesting that impairment of mammary tight junction integrity is associated with decreased milk secretion during an extended milking interval. The decline in mammary blood flow may be the result of a negative feedback response to a reduced demand for metabolites, which is due to a reduced rate of milk secretion.

Animals↗
PubMed1994

Effect of once daily milking and concurrent somatotropin on mammary tight junction permeability and yield of cows.

Six pairs of monozygous Friesian twin cows during late lactation were used to assess the effect of once daily milking and bST treatment on yields and tight junction permeability of mammary epithelial cells. During the first 7 d, all cows were milked twice daily; on d 8 through d 21, all cows were milked once daily, but one cow of each twin pair was treated daily with 20 mg of bST on d 13 through 21; and, finally, during d 22 through 28, all cows were again milked twice daily. Once daily milking, a common management practice in New Zealand, resulted in a small (7%) but significant decrease in milk yield. Treatment with bST increased milk yield by 19%, thereby exceeding the milk yield loss from once daily milking. The integrity of mammary tight junctions was assessed indirectly by measuring concentrations of plasma lactose and milk BSA. Once daily milking temporarily disrupted tight junction integrity, based on a 4- to 5-fold increase in plasma lactose and a 42 to 55% increase in the concentrations of milk BSA. In the present study, bST did not affect the permeability of mammary tight junctions.

Animals↗