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Biomedical subjects

R O Gilbert

Publications and source records attributed to R O Gilbert.

At least 19 recordsLinked to original sources

Effects of feeding fish meal and n-3 fatty acids on milk yield and metabolic responses in early lactating dairy cows.

The study was designed to test the effects of feeding fish meal (FM) and specific n-3 fatty acids on milk yield and composition, dry matter intake, plasma concentrations of metabolic hormones and metabolites, and liver triglyceride accumulation in early lactating cows. From 5 to 50 d in milk (DIM), cows were fed diets that were isonitrogenous, isoenergetic, and isolipidic containing none (control), 1.25, 2.5, or 5% menhaden FM or 2.3% Ca salts of fish oil fatty acids (CaFOFA). Milk yield (48.2, 49.8, 48.6, 53.5, and 52.2 +/- 1.0 kg/d, respectively) and dry matter intake (22.7, 22.8, 23.0, 23.8, and 24.7 +/- 0.5 kg/d, respectively) differed among diets. Average daily plasma glucose concentration (53.4, 55.3, 51.1, 57.6, and 57.3 +/- 1.3 mg/dL, respectively) was also affected by diet, and plasma insulin concentration was increased by 5% FM and 2.3% Ca-FOFA. At 25 and 50 DIM, blood was collected before feeding and hourly for 11 h after feeding. Plasma glucose concentrations in cows during the day were similar among diets at 25 DIM, but differed at 50 DIM (54.6, 54.4, 52.4, 60.5, and 58.3 +/- 1.4 mg/dL for 0, 1.25, 2.5, and 5% FM or 2.3% CaFOFA, respectively). Plasma insulin was increased in cows fed 5% FM and 2.3% CaFOFA at 25 DIM and was similar among diets at 50 DIM. Dietary treatments had no significant effect on milk composition, energy balance, or on daily plasma concentrations of nonesterified fatty acids, beta-hydroxybutyrate, and urea. Plasma aspartate aminotransferase and hepatic triglyceride concentration in cows did not differ among diets at 21 DIM. Results from this experiment demonstrate that dietary supplementation with FM or n-3 polyunsaturated fatty acids in early lactating dairy cows significantly increased milk yield and DMI with no change in milk composition.

Animals↗

Effects of feeding fish meal and n-3 fatty acids on ovarian and uterine responses in early lactating dairy cows.

The study was designed to test the effects of dietary supplementation with fish meal or specific n-3 fatty acids on ovarian activity and uterine responses in early lactating cows. From 5 to 50 d in milk (DIM), cows were fed diets that were isonitrogenous, isoenergetic, and isolipidic containing none (control), 1.25, 2.5, or 5% menhaden fish meal (FM) or 2.3% Ca salts of fish oil fatty acids (CaFOFA). Ovarian follicular dynamics were monitored along with plasma concentrations of estradiol and progesterone. Beginning at 23 DIM, cows were induced into a synchronized ovulatory cycle. On d 15 after ovulation (49 DIM), cows were injected with oxytocin and blood samples were collected to monitor uterine release of PGF(2alpha) (measured as 13, 14-dihydro-15-keto PGF(2alpha); PGFM). Uterine endometrial biopsies were collected for fatty acid analysis and cyclooxygenase-2 (COX-2) protein measurement. Ovarian follicular activities as well as plasma estradiol and progesterone concentrations were similar across diets. Endometrial fatty acid composition of eicosapentaenoic acid (C20:5, n-3) and docosahexaenoic acid (C22:6, n-3) were increased as much as 3-fold by supplementation with fish meal and CaFOFA. Conjugated linoleic acid (C18:2 cis-9, trans-11) in the endometrium was also increased; conversely, arachidonic acid (C20:4, n-6) percentage was decreased by 5% FM. Plasma PGFM response to oxytocin injection was not different among diets and endometrial COX-2 protein abundance did not differ. Results from this experiment demonstrate that dietary supplementation with fish meal or n-3 fatty acids in early lactating dairy cows significantly increased uterine n-3 fatty acid concentrations, but had no apparent effect on endometrial COX-2 or PGF(2alpha) production in response to oxytocin challenge.

Animal Feed↗

Relationship of pre-ovulatory follicle size, estradiol concentrations and season to pregnancy outcome in dairy cows.

This study was carried out to evaluate effects of pre-ovulatory follicle size, plasma concentrations of estradiol and progesterone, and season on pregnancy outcomes in dairy cows. Holstein cows (n = 144) were synchronized and inseminated (Ovsynch/TAI protocol) in two distinct periods (cold versus warm season). Blood samples were collected daily from AI (day 0) to day 8 and on days 15, 22, 29, 36 and 64 to measure progesterone and estradiol. Pregnancy diagnosis was performed at days 29, 43 and 64. The pre-ovulatory follicle size was larger and the plasma estradiol concentrations on the day of AI were greater in animals that became pregnant. Plasma progesterone concentrations diverged and became greater after day 5 post-AI, in cows diagnosed pregnant, as compared to non-pregnant cows. The overall pregnancy rate (33%) or late embryonic/early fetal losses (23%) did not differ between seasons, but plasma estradiol concentrations on the day of AI and plasma concentrations of progesterone in pregnant cows were lower in the warm season. Reduced CL function, measured as plasma progesterone concentrations, from days 22 or 29 post-AI onward for cold and warm season, respectively, was associated with subsequent late embryonic/early fetal mortality. Overall, pregnancy was related to diameter of the pre-ovulatory follicle and plasma E2 on the day of AI, but embryonic/fetal losses were not. Season did not affect these outcomes, even though it influenced luteal function after AI.

Abortion, Veterinary↗

Detrimental effects of high plasma urea nitrogen levels on viability of embryos from lactating dairy cows.

High plasma urea nitrogen (PUN) concentrations are associated with decreased fertility in lactating dairy cows. Our objective was to evaluate the quality of embryos flushed from superovulated lactating cows having moderate or high PUN concentrations. Subsequent embryo survival was determined after transfer to recipient heifers with either low or high PUN. Lactating Holstein dairy cows (n = 23; 50-120 days in milk) were randomly assigned to one of two diets designed to result in moderate or high PUN concentrations (15.5 +/- 0.7 and 24.4 +/- 1.0 mg/dl, respectively; P < 0.001) and were fed for 30 days before embryo flushing and recovery. Embryos (n = 94) were evaluated morphologically, frozen and subsequently transferred into synchronized virgin heifers that were fed one of two diets designed to result in either low or high PUN concentrations (7.7 +/- 0.9 and 25.2 +/- 1.5 mg/dl, respectively; P < 0.001; 2 x 2 factorial design). The number, quality and stage of development of recovered embryos were similar for cows with moderate or high PUN. Transfer of embryos from moderate PUN donor cows resulted in a higher pregnancy rate (35%; P < 0.02) than the transfer of embryos from high PUN donor cows (11%). Pregnancy rate was not affected by either recipient diet or the interaction of donor and recipient diets (P > 0.05). These results indicate that high PUN concentrations in lactating dairy cows decrease embryo viability through effects exerted on the oocyte or embryo before recovery from the uterus 7 days after insemination.

Animal Feed↗

Tritrichomonas foetus induces apoptotic cell death in bovine vaginal epithelial cells.

Tritrichomonas foetus is a serious veterinary pathogen, causing bovine trichomoniasis, a sexually transmitted disease leading to infertility and abortion. T. foetus infects the mucosal surfaces of the reproductive tract. Infection with T. foetus leads to apoptotic cell death of bovine vaginal epithelial cells (BVECs) in culture. An affinity-purified cysteine protease (CP) fraction yielding on sodium dodecyl sulfate-polyacrylamide gel electrophoresis a single band with an apparent molecular mass of 30 kDa (CP30) also induces BVEC apoptosis. Treatment of CP30 with the protease inhibitors TLCK (Nalpha-p-tosyl-l-lysine chloromethyl ketone) and E-64 [l-trans-epoxysuccinyl-leucylamide-(4-guanido)-butane] greatly reduces induction of BVEC apoptosis. Matrix-assisted laser desorption ionization-time-of-flight MALDI-TOF mass spectrometry analysis of CP30 reveals a single peak with a molecular mass of 23.7 kDa. Mass spectral peptide sequence analysis of proteolytically digested CP30 reveals homologies to a previously reported cDNA clone, CP8 (D. J. Mallinson, J. Livingstone, K. M. Appleton, S. J. Lees, G. H. Coombs, and M. J. North, Microbiology 141:3077-3085, 1995). Induction of apoptosis is highly species specific, since the related human parasite Trichomonas vaginalis and associated purified CPs did not induce BVEC death. Fluorescence microscopy along with the Cell Death Detection ELISA(PLUS) assay and flow cytometry analyses were used to detect apoptotic nuclear condensation, DNA fragmentation, and changes in plasma membrane asymmetry in host cells undergoing apoptosis in response to T. foetus infection or incubation with CP30. Additionally, the activation of caspase-3 and inhibition of cell death by caspase inhibitors indicates that caspases are involved in BVEC apoptosis. These results imply that apoptosis is involved in the pathogenesis of T. foetus infection in vivo, which may have important implications for therapeutic interference with host cell death that could alter the course of the pathology in vivo.

Animals↗

Effects of urea infusion on the uterine luminal environment of dairy cows.

Previous research indicates that high plasma urea nitrogen (PUN) concentrations are associated with decreased fertility in lactating dairy cows. The objective of this study was to monitor changes in the uterine environment during acute elevation of PUN. Lactating dairy cows (n = 8) were infused with saline or urea (0.01 g of urea/h per kg of body weight) through jugular vein catheters on d 7 after estrus. After 24 h, cows were switched to the opposite treatment for a second 24-h infusion period. Blood samples were collected every 2 h, and the pH within the lumen of the uterine horn ipsilateral to the corpus luteum was recorded every 6 h. At the end of each 24-h infusion period, 30 mL of sterile saline was flushed into the uterine lumen and immediately retrieved. Mean PUN concentration increased from 16.6 +/- 1.3 mg/dL during saline infusion to 22.6 +/- 1.3 mg/dL during urea infusion. Uterine pH decreased during urea infusion from 7.08 +/- 0.07 at 6 h to 6.88 +/- 0.08 at 18 h, but was unchanged during saline infusion (7.01 +/- 0.08 at 6 h to 7.06 +/- 0.07 at 18 h). Protein concentration, PGF(2alpha), and prostaglandin E(2) concentrations in uterine lavage samples were not different between treatments. The results of this study indicate that a short-term increase in PUN can exert direct effects on the uterine environment by decreasing uterine pH.

Animals↗

Cytopathogenic effect of Trichomonas vaginalis on human vaginal epithelial cells cultured in vitro.

In this study we established human vaginal epithelial cells (hVECs) in culture and evaluated their interaction with Trichomonas vaginalis parasites to complement previous studies using other cell types. Primary cultures of hVECs were established. Contaminating fibroblasts were separated from epithelial cells by differential trypsinization. Specific antibody staining revealed that over 92% of cells in hVEC monolayers were epithelial cells. T. vaginalis adhered to hVECs and produced severe cytotoxic effects resulting in obliteration of the monolayer within 24 h. Adherence and cytotoxicity were not observed when T. vaginalis was exposed to human vaginal fibroblasts or bovine vaginal epithelial cells. Likewise, the bovine parasite Tritrichomonas foetus had no cytotoxic effects on hVECs. We concluded that the interaction between T. vaginalis and hVECs is both cell specific (limited to epithelial cells and not vaginal fibroblasts) and species specific (limited to human vaginal cells and not bovine cells). Pretreatment of T. vaginalis with metronidazole or periodate abolished the adhesion of parasites to cell monolayers and the cytotoxic effect, suggesting involvement of carbohydrate-containing molecules in these processes. Different clinical isolates of T. vaginalis caused damage to cultured cells at different rates. Parasites separated from the vaginal cell monolayer by a permeable membrane did not produce a cytopathic effect, suggesting contact-dependent cytotoxicity.

Animals↗

Detection of bovine immunodeficiency virus DNA in the blood and semen of experimentally infected bulls.

Five 18- to 24-month-old bulls were inoculated with either a cell suspension containing bovine immunodeficiency virus (BIV-FL112; 3 bulls) or a BIV-free cell suspension (2 bulls). Blood and semen specimens were collected once a week for 14 weeks, and seroconversion was confirmed by indirect immunofluorescent antibody (IFA) testing. The presence of BIV in blood and semen was determined by virus isolation and/or polymerase chain reaction (PCR) assays. Antibodies to BIV were detected in the 3 experimentally infected bulls as early as day post inoculation (DPI) 17, and levels peaked at DPI 37-58. BIV was isolated from the peripheral blood mononuclear cells (MNCs) of the infected bulls at DPI 9 (2 bulls) and DPI 23 (1 bull), and could be isolated from one animal up to DPI 65. PCR analysis of MNC DNA, using BIV pol gene primers, detected virus in all three of the experimentally infected bulls from DPI 9 until the termination of the experiment at DPI 98. Efforts to isolate a significant number of non-spermatozoal cells (NSC) by gradient separation from the semen of the experimentally infected bulls were unsuccessful. Two methods for the extraction of total NSC DNA from up to 2 ml of non-extended semen were employed; however, no BIV pol fragment was amplified from these DNA preparations. Additionally, 30 bulls from artificial insemination (AI) centers were evaluated for BIV infection by PCR. No amplification products were obtained from MNC DNA from the AI submissions using primer sets for both the BIV pol and env genes.

Animals↗

Adhesion of Tritrichomonas foetus to bovine vaginal epithelial cells.

An in vitro culture system of bovine vaginal epithelial cells (BVECs) was developed to study the cytopathogenic effects of Tritrichomonas foetus and the role of lipophosphoglycan (LPG)-like cell surface glycoconjugates in adhesion of parasites to host cells. Exposure of BVEC monolayers to T. foetus resulted in extensive damage of monolayers. Host cell disruption was measured quantitatively by a trypan blue exclusion assay and by release of (3)H from [(3)H]thymidine-labeled host cells. Results indicated contact-dependent cytotoxicity of host cells by T. foetus. The cytopathogenic effect was a function of T. foetus density. Metronidazole- or periodate-treated T. foetus showed no damage to BVEC monolayers. A related human trichomonad, Trichomonas vaginalis, showed no cytotoxic effects, indicating species-specific host-parasite interactions. A direct binding assay was developed and used to investigate the role of a major cell surface LPG-like molecule in host-parasite adhesion. The results of competition experiments showed that the binding to BVECs was displaceable, was saturable, and yielded a typical binding curve, suggesting that specific receptor-ligand interactions mediate the attachment of T. foetus to BVECs. Progesterone-treated BVECs showed enhanced parasite binding. T. foetus LPG inhibited the binding of T. foetus to BVECs; the LPG from T. vaginalis and a variety of other glycoconjugates did not. These data imply specificity of LPG on host-parasite adhesion. Periodate-treated parasites showed no adherence to host cells, indicating the involvement of carbohydrate containing molecules in the adhesion process.

Animals↗

Onset of epiphyseal mineralization and growth plate closure in radiographically normal and dysplastic Labrador retrievers.

OBJECTIVE: To determine whether onset of mineralization of the femoral and proximal tibial epiphyses and age at closure of the femoral and acetabular triradiate growth plates was different for Labrador Retrievers that were radiographically normal or that had canine hip dysplasia (CHD). DESIGN: Cohort study. ANIMALS: 36 Labrador Retriever puppies. PROCEDURE: Puppies were radiographed every other day from the time they were 8 to 10 days old until ossification of the femoral heads was apparent. Radiographs were then obtained weekly until puppies were 1 month old and then monthly until puppies were 8 to 12 months old. Age at which mineralization was first observed in the proximal and distal femoral and proximal tibial epiphyses and at which the femoral capital, triradiate acetabular, and distal femoral growth plates were no longer radiographically visible were recorded. Fifteen dogs were euthanatized and necropsied to determine whether dogs had CHD. RESULTS: There were 26 radiographically normal left and right hip joints and 10 dysplastic left and right hip joints. Onset of mineralization of the proximal femoral epiphyses and of the right proximal tibial epiphysis was significantly later in dysplastic than in radiographically normal puppies. The left femoral capital growth plates closed significantly later in dysplastic than in radiographically normal joints, but other differences in growth plate closure were not detected. CLINICAL IMPLICATIONS: Endochondral ossification may be abnormal in dogs with CHD. The disease appears to affect multiple joints, even though it is most evident clinically in the hip joint.

Aging↗

The effect of bovine seminal plasma on the function and integrity of bovine neutrophils.

Spermatozoa, by virtue of their high content of polyunsaturated fatty acids and limited antioxidant activity, are highly sensitive to lipid peroxidation. Sources of reactive oxygen species in the female genital tract include neutrophils recruited in response to insemination or those contained within the ejaculate, or even spermatozoa themselves. This study was undertaken to investigate the effect of seminal plasma of bulls on bovine neutrophils. Seminal plasma was removed from ejaculates of 6 healthy bulls by centrifugation. Neutrophils were isolated from jugular venous blood samples obtained from lactating Holstein cows. Seminal plasma was found to decrease measured Superoxide anion production by activated neutrophils (P = 0.008) in a concentration-dependent manner over the range tested (0 to 16%). This effect may reflect Superoxide scavenging by the seminal plasma or direct inhibition of the neutrophils. It has the potential physiological advantage of protecting spermatozoa from oxidative damage. Seminal plasma was found to reduce homotypic neutrophil aggregation dramatically (P < 0.0001). At a seminal plasma concentration of 0.2% neutrophil aggregation was virtually abolished. Homotypic neutrophil aggregation depends on the CD 11b/CD 18 (Mac-1) receptor, which also functions as the C3bi receptor (known as complement receptor-3 or CR3). If this receptor is down-regulated, the ability of neutrophils to phagocytose complement-opsonized microorganisms would be compromised. Finally, seminal plasma was found to increase neutrophil permeability to trypan blue in a concentration and time dependent fashion (P < 0.0001), indicating a direct cytotoxic effect. Taken together, these findings indicate a profound inhibition of neutrophil function by bovine seminal plasma. While these mechanisms are likely to protect spermatozoa from oxidative damage or phagocytosis, they also have the potential to diminish defense against pathogenic microorganisms.

Journal Article↗

Uncertainty of historical measurements of 131I in Hanford-area vegetation.

The Hanford Environmental Dose Reconstruction (HEDR) Project was conducted to estimate the radiation dose that individuals could have received as a result of emissions to the air and water from Hanford Site operations since 1944. The largest doses were to the human thyroid gland from 131I released into the atmosphere from Hanford facilities in the 1945-1947 time period. In support of the dose reconstruction effort, a database of historical environmental radioactivity measurements was constructed. This database includes measurements of total radioactivity for vegetation samples collected from 1945-1948 and counted using a Geiger-Mueller (GM) detector system. Because the factors used at that time to convert the GM counts to 131I activity did not take all parameters into account, and because some parameter values were inaccurate, more accurate conversion factors were developed as part of the HEDR Project. These factors can be used to estimate the actual historical activity levels. This paper summarizes the Monte Carlo uncertainty and sensitivity analysis methods used to assess the uncertainty of the newly reconstructed historical vegetation 131I activities and to identify the parameters that contributed the most uncertainty to these reconstructed activities. Based on the study of two vegetation (sagebrush) samples collected in the mid-1940's, it appears that the true 131I activity of the historical vegetation samples should be within a factor of three of the reconstructed activity. Also, the uncertainty in the parameter Icf (the fraction of the background-corrected GM measurement of a vegetation sample that resulted from 131I) was found to contribute the most uncertainty to the reconstructed 131I activities when the uncertainty in Icf was large.

Air Pollutants, Radioactive↗

Postpartum anestrus in French beef cattle: an epidemiological study.

Postpartum anestrus of lactating beef cows was studied by means of an epidemiological study carried out on 878 lactating beef cows in 60 French herds. The cows calved between October 1992 and March 1993 and were housed 2 mo after calving, when the anestrus status was determined by progesterone radioimmunoassays. Data analysis was performed using a multiple logistic model in order to adjust for confounding and interaction. Fifty-one percent of the primiparous and 23% of the multiparous cows were found to be in anestrus. Factors significantly related to anestrus were parity (primiparous); breed (Charolais); housing type (tie housing); suckling (compared to weaning at birth); and, among those that were under the control of the farmer, calving conditions (manual exploration of the birth canal); body condition score at calving (3 or less, on a 5-point scale); and loss in body condition score after calving (1 point or more within 2 mo). Previous reproductive performance for multiparous cows such as a long calving interval and induced estrus in the previous year also appeared to be related to anestrus.

Journal Article↗

Clinical manifestations of leukocyte adhesion deficiency in cattle: 14 cases (1977-1991).

In Holstein cattle, an inherited disease has been recognized recently in which leukocytes lack surface glycoproteins termed beta 2 integrins, which are important in cell adhesion processes. This disease is the homologue of leukocyte adhesion deficiency in human beings and has been termed bovine leukocyte adhesion deficiency. The molecular basis of this disease is failure to produce normal CD18. The gene encoding bovine CD18 and its abnormal mutation have been sequenced, allowing specific diagnosis of the condition by DNA amplification by polymerase chain reaction followed by specific endonuclease digestion. This test was applied to formalin-fixed archival tissues from 18 cattle that had been admitted to the veterinary medical teaching hospital between 1975 and 1991 and that had had persistent and severe neutrophilia. Blood samples were collected from 2 additional cattle, and leukocytes from these samples also were tested. Fourteen cattle were confirmed to have been homozygous for the bovine leukocyte adhesion deficiency gene. Cattle with this condition had ranged in age from 2 weeks to 8 months at admission. They typically had had chronic bacterial infections that had failed to respond to or had recurred after conventional treatment. Consistent findings in these cattle included signs of bronchopneumonia, gingivitis, periodontitis, and peripheral lymphadenopathy. Severe neutrophilia, usually without a left shift, was a hallmark of the disease; consistent clinical biochemical findings included hypoalbuminemia, hyperglobulinemia, and hypoglycemia. This disease is important because it mimics common calfhood diseases such as pneumonia and diarrhea, but is ultimately consistently fatal before adulthood.

Animals↗

Impaired post partum neutrophil function in cows which retain fetal membranes.

The post partum neutrophil function in cows which had retained fetal membranes (RFM) for at least 24 hours post partum were compared with matched herdmates which had not retained their fetal membranes. Cows from a single dairy herd which had spontaneously occurring RFM (n = 8) were matched with herdmates (n = 8) which had calved within 48 hours before or after them and had not experienced RFM. Blood samples were collected from the cows three times post partum: two to five days, three weeks and six weeks. Neutrophils were isolated by differential centrifugation followed by hypotonic lysis of erythrocytes. In vitro neutrophil function was assessed by superoxide anion (O2-) generation and by stimulus-induced shape change. Neutrophils from cows with RFM produced significantly less superoxide anion during the first week post partum and six weeks post partum. Cows with RFM had impaired neutrophil shape change immediately post partum. Shape change responsiveness increased in both groups from the first post partum week to three weeks post partum.

Animals↗

Effect of parity on periparturient neutrophil function in dairy cows.

Impairment of periparturient neutrophil function in dairy cows has been described. This may contribute to increased susceptibility of cows to bacterial infections during the periparturient period. Susceptibility to many complications of the postpartum period is influenced by parity. The aim of this experiment was to determine whether parity influenced periparturient neutrophil function in Holstein cows. Cows (n = 46, of which 26 were calving for the first, second or third time, and 20 were of more advanced parity) were sampled during the last prepartum week, the first postpartum week, 3 weeks postpartum and 6 weeks postpartum. Neutrophils were isolated by centrifugation and hypotonic lysis of erythrocytes. Neutrophil superoxide anion production was determined by the superoxide dismutase inhibitable reduction of ferricytochrome c, and stimulus-induced shape change was determined at 0, 30, 60 and 120 s after exposure to zymosan activated bovine plasma. Superoxide anion production was significantly depressed in the first postpartum week in all cows. At this time, superoxide anion production was significantly lower in cows in their fourth or greater lactation than in cows in the first three lactations. Neutrophil shape change responsiveness was also influenced by parity; immediately prepartum, the shape change responsiveness differed between groups at 120 s after application of the stimulus, and during the first postpartum week shape change responsiveness was less in cows of advanced parity at 30, 60 and 120 s after application of the stimulus. We concluded that cows in the fourth or greater lactation suffered more profound periparturient impairment of neutrophil function than younger cows and that this may be a factor mediating their increased susceptibility to some postpartum complications.

Animals↗

Identification and prevalence of a genetic defect that causes leukocyte adhesion deficiency in Holstein cattle.

Two point mutations were identified within the gene encoding bovine CD18 in a Holstein calf afflicted with leukocyte adhesion deficiency (LAD). One mutation causes an aspartic acid to glycine substitution at amino acid 128 (D128G) in the highly conserved extracellular region of this adhesion glycoprotein, a region where several mutations have been found to cause human LAD. The other mutation is silent. Twenty calves with clinical symptoms of LAD were tested, and all were homozygous for the D128G allele. In addition, two calves homozygous for the D128G allele were identified during widespread DNA testing, and both were subsequently found to exhibit symptoms of LAD. The carrier frequency for the D128G allele among Holstein cattle in the United States is approximately 15% among bulls and 6% among cows. This mutation is also prevalent among Holstein cattle throughout the world, placing this disorder among the most common genetic diseases known in animal agriculture. All cattle with the mutant allele are related to one bull, who through the use of artificial insemination sired many calves in the 1950s and 1960s. The organization of the dairy industry and the diagnostic test described herein will enable nearly complete eradication of bovine LAD within 1 year. These results also demonstrate that bovine LAD is genetically homologous and phenotypically similar to human LAD, thus providing a useful animal model for studies of LAD and beta 2 integrin function.

Alleles↗

Pharmacologic considerations in the management of peripartum conditions in the cow.

As is true with the use of drugs in veterinary medicine in general, there are many controversial issues in the management of peripartum conditions in the cow. For example, the use of PG versus antibacterial drugs in the management of postpartum uterine infections has advocates for the use of either approach. Intrauterine versus systemic administration of antibacterial drugs for the prophylaxis or treatment of postpartum metritis is another area of debate. Clearly, more research is needed in this area. Equally clearly, however, the research results that are available are being disregarded on a daily basis. In considering this discussion of the use of drugs in the peripartum period, one is struck by the frequency that optimum drug therapy of a condition relies on the extralabel use of nonapproved preparations. What guidelines are available to the practitioner in this regard? One example is lack of availability of appropriate dosage regimens or withdrawal times for food derived from treated animals. Unfortunately, pharmacokinetic and residue studies that would aid in establishing guidelines generally are not available and, in most instances, are not forthcoming. Extrapolation of data from other species to the ruminant or extrapolation of information from one drug to a related compound (such as prediction of residue and withdrawal data from an approved aminoglycoside, dihydrostreptomycin, to another unapproved drug, gentamicin) is fraught with difficulties. The need for research in this area is obvious, and lack of such information is one of the major dilemmas in trying to establish rational drug therapy in the food-producing animal. Recent developments in drug therapy have led to innovative approaches for the management of peripartum and other diseases in cattle. The use of PG in the treatment of reproductive disorders, so commonplace and widely accepted in contemporary veterinary practice, is a relatively recent approach that continues to be refined with the development of new, more potent, more specific PG analogs. What will be the role of ceftiofur, a potent, third-generation cephalosporin that currently is approved only for the treatment of respiratory infections in cattle, in the management of reproductive tract infections? The fluoroquinolones, which represent a novel approach to the control of infectious diseases, are being increasingly used in veterinary and human medicine, and one may predict that these powerful antimicrobial drugs will find application in bovine practice, including for the treatment of peripartum infections. Pharmacologic manipulation of immune and defense mechanisms also is an approach with some promise.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗