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Biomedical subjects

D H Schlafer

Publications and source records attributed to D H Schlafer.

At least 19 recordsLinked to original sources
PubMed2004

Major histocompatibility antigen expression on the bovine placenta: its relationship to abnormal pregnancies and retained placenta.

In viviparous animals, regulation of expression of major histocompatibility complex (MHC) class I antigens by the trophoblast cells, which constitute the outermost layer of the placenta, seems to be critical for maternal immunological acceptance of an allogeneic fetus. Cattle are unusual in this regard, since the bovine trophoblast cells, in specific regions of the uterine/placental interface, normally express MHC class I antigens during the third trimester of gestation. This expression appears to be biologically relevant as MHC class I compatibility between a cow and her fetus has been associated with an increased incidence of placental retention. We have found significant differences in lymphocyte populations, cytokine production, and trophoblast cell apoptosis in the placentomes of MHC-compatible and -incompatible pregnancies at parturition. This suggests that maternal immunological recognition of fetal MHC class I proteins triggers an immune/inflammatory response that contributes to placental separation at parturition in cattle. Early in pregnancy, a complete shutdown of MHC class I expression by trophoblast cells appears to be critical for normal placental development and fetal survival. In bovine somatic cell nuclear transfer (SCNT) pregnancies, there is an extremely high rate of fetal loss between days 30 and 90 of pregnancy. We have shown that in bovine SCNT pregnancies, between days 34 and 63 of gestation, there is both abnormal expression of MHC class I antigens by trophoblast cells and an abnormal accumulation of lymphocytes within the uterine stroma. Consequently, it is likely that activation of the maternal mucosal immune system, within the uterus at the same time when placentomes are being established, interferes with the process of placentome development and leads to immune-mediated abortion. Our data suggest that bovine MHC-compatible pregnancies provide a unique model for studying regulation of the uterine immune system, as well as immune-mediated placental rejection.

Abortion, Veterinary↗
PubMed2003

Maternal dexamethasone increases endothelin-1 sensitivity and endothelin a receptor expression in ovine foetal placental arteries.

Despite National Institutes of Health recommendations to administer antenatal steroids as a single course to women threatening preterm delivery, repeated treatments are often given. We investigated effects of repeated dexamethasone (DM) administered to the ewe on small maternal and foetal placental arteries. We hypothesized that DM would increase responsiveness to endothelin-1 (ET-1) and norepinephrine (NE) and that foetal arteries would react differently to ET-1 and NE compared to maternal arteries. Ewes received three treatments beginning at 103, 110, and 117 days of gestation (dGA). Each treatment consisted of four IM injections of 2mg DM or saline at 12-h intervals. At 119 dGA, in vitro functional studies were performed using Mulvany wire myography and endothelin receptor (ETR) expression was quantified using real-time RTPCR and receptor ligand autoradiography. Foetal placental arteries demonstrated greater maximal contractility to ET-1 and lesser maximal contractility to NE compared to maternal arteries. DM increased the maximal contraction elicited by ET-1 and NE in foetal but not maternal placental arteries. DM also increased the abundance of type-A ETR but not type-B ETR mRNA in foetal but not maternal placental arteries. However, within the whole placentome, DM increased the abundance of type-B ETR and decreased type-A ETR mRNA, which was confirmed by similar changes in ETR binding specifically within the labyrinth region. In summary, repeated DM treatment results in agonist and vascular bed specific responses within the placenta.

Animals↗
PubMed2001

A spontaneously occuring mammary gland ductal carcinoma in situ in a rhesus macaque (Macaca mulatta) and a review of spontaneous mammary gland tumors in rhesus monkeys.

A spontaneous mammary gland ductal carcinoma in situ was diagnosed in a 6-8-year-old female rhesus macaque (Macaca mulatta). To our knowledge, this is only the tenth case of spontaneous mammary gland tumors to be reported in rhesus monkeys. Despite the paucity of case reports, several theories exist to explain the occurrence of mammary tumors. The Mason Pfizer monkey virus, a type D retrovirus similar to the virus that causes simian acquired immunodeficiency syndrome, has been implicated as a possible etiologic agent. Because this virus has been isolated from normal primate mammary tissue, it is unlikely to be the sole etiologic agent. Other theories include the tumorogenic effects that androgens, growth hormones, irradiation, and aging have on the mammary gland.

Animals↗
PubMed2001

Characterization of trophoblast cell populations by lectin histochemistry in canine placenta during development.

The aim of this study was to identify and characterize populations of trophoblast cells in canine placenta during different stages of fetal development using lectin histochemistry. Dogs have endotheliochorial placentation and trophoblast cell invasion continues after chorioallantois villous penetration early in pregnancy, leading to formation of a labyrinth. Specialized subpopulations of cells differentiate, such as syncytial trophoblast that invades the maternal epithelium early in placentation and surrounds and forms intimate cuffs around maternal blood vessels. Marginal haematomata, which are lined by specialized phagocytic cytotrophoblast cells, form by mid-gestation. Invasive 'extravillous' cells advance into and remodel maternal endometrial tissues further. Placentas and attached uterine tissues were collected and sampled from six bitches at mid-gestation (days 31-33 of gestation) and 12 females in late gestation (day 42-term) for characterization of these tissues and identification of other populations of trophoblast cells. Uterine tissues from nonpregnant bitches were also collected at oestrus (n = 2) and during the luteal phase (n = 1). In histochemical studies, two of six biotinylated lectins that were tested stained cytotrophoblast and syncytial trophoblast cell populations differentially. Arachis hypogaea agglutinin (PNA) was specific for cytotrophoblasts in placental tissue lining villi and cytotrophoblastic cells with phagocytic or absorptive phenotypes in the necrotic zone at mid-gestation. In late gestation, cytotrophoblast cells with an absorptive phenotype at the interface between the labyrinth and lacunar glandular chambers were stained with PNA. Staining of other cells was minimal, with the exception of deep endometrial glands. Lectin binding using Maclura pomifera agglutinin (MPL) specifically stained the same cells as PNA and the population of invasive syncytial trophoblast cells remodelling maternal blood vessels and small maternal vessels at the materno-fetal interface, as well as trophoblast cells within necrotic zones at mid-gestation. Both lectins were positive for phagocytic cytotrophoblast cells lining the haematophagus organs. The results of this study demonstrate that lectin histochemistry is a useful tool for staining subpopulations of cytotrophoblast and syncytial trophoblast cells.

Animals↗
PubMed2000

The bovine placenta before and after birth: placental development and function in health and disease.

This paper reviews bovine placental development, anatomy (microscopic and gross), nomenclature and classification. The paper focuses on the biology of those specialized cells that arise from the outermost layer of very early embryos, the trophoblast cells, and on placental macrophages, cells that play a key role in fetal/placental defense. Data is presented from an immunohistochemical quantitative study that characterizes the ontogeny of placental macrophages using placental tissues from 21 cows (sampled from 4 months of pregnancy through the post partum period). Understanding of bovine placental development is essential for veterinarians, pathologists, diagnosticians and researchers. Lesions of diagnostic significance can be recognized for many economically important infectious abortifacient diseases, and there is growing evidence that pregnancy failure of cloned calves is due in part to unexplained placental failure. Placentology and placental pathology are becoming of increasing importance.

Animals↗
PubMed2000

Caprine genital leiomyosarcoma.

An aged Saanen doe was euthanized following repeated severe hemorrhage from the vulva. Necropsy examination revealed mural thickening of tubular genitalia with firm, protruding intralumenal masses containing blood-filled cavitations, and effacement of normal cervical architecture. Histologically, uterine and cervical masses comprised a variably dense population of mildly pleomorphic spindle cells forming interlacing streams supported by variably dense collagenous stroma. Immunoperoxidase staining of neoplastic cells was positive for muscle-specific actin, supporting the diagnosis of low-grade leiomyosarcoma. Months later, the doe's twin was likewise euthanized due to persistent bleeding from the vulva associated with a large vulvar mass having histopathologic features similar to those of the previous case. The clinical, gross, and histologic findings are similar to five cases of caprine genital leiomyosarcoma identified in retrospectively analyzed case material. Analysis of caprine tumor accessions over 20 years demonstrated a significantly higher incidence of genital leiomyosarcoma within the Saanen breed.

Animals↗
PubMed1997

Proteinuric hypertension in a pregnant baboon: was this pre-eclampsia?

We report the results of investigating a pregnant baboon that developed hypertension, proteinuria, and oedema in late gestation. Although the clinical presentation suggested a diagnosis of pre-eclampsia, the evolution of her clinical signs and results of a renal biopsy performed 3 weeks after delivery suggested that glomerulonephritis was the underlying disease.

Aged↗
PubMed1997

Equine viral arteritis in newborn foals: clinical, pathological, serological, microbiological and immunohistochemical observations.

Clinical, pathological, immunohistochemical, serological and microbiological findings are described for 2 geographically and temporally distinct equine arteritis virus (EAV) epidemics in newborn foals. Outbreak A occurred at a commercial Standardbred breeding facility; Outbreak B began in a group of research animals. Clinical signs were severe and primarily referable to the respiratory tract. Fever and leucopenia and/or thrombocytopenia were observed in foals surviving for more than 24 h. The most common gross pathological findings were limited to the respiratory tract. Common histopathological findings included interstitial pneumonia, lymphocytic arteritis and periarteritis with fibrinoid necrosis of the tunica media. Renal tubular necrosis was noted in 2 foals. Immunoperoxidase histochemistry combined with virus isolation was diagnostic in all cases.

Animals↗
PubMed1995

A comparison of three avidin-biotin complex immunoenzyme systems for detection of African swine fever virus antigen in paraffin-embedded tissues.

The sensitivity and specificity of 3 avidin-biotin complex (ABC) immunostaining systems were compared on paraffin-embedded tissues from African swine fever virus (ASFV)-infected pigs. Results were also compared with immunofluorescent detection on cryosections of the same tissue for optimal detection of ASFV antigen. The ABC-alkaline phosphatase (ABC-AP) and ABC-peroxidase (ABC-PO) systems were at least as sensitive as direct fluorescent antibody (FA) and 10-fold more sensitive than the ABC-glucose oxidase system. Three ABC-AP and 2 ABC-PO chromagens with different counterstains were compared. In addition, 2 fixatives, 2 biotinylation procedures, 7 endogenous peroxidase blocking regimes, 6 tissue adhesives, and 3 mounting media were compared. The ABC-AP system with a red chromagen and hematoxylin counterstaining was preferred and most closely approximated routinely stained pathologic sections. Fixation in paraformalde-hydelysine-periodate fixative preserved ASFV antigen for research studies for at least 3 years. Formalin-fixed tissues retained some staining for up to 10 years.

African Swine Fever Virus↗
PubMed1995

Early infection of interdigitating dendritic cells in the pig lymph node with African swine fever viruses of high and low virulence: immunohistochemical and ultrastructural studies.

The role of interdigitating dendritic cells (IDCs) in the early pathogenesis of African swine fever (ASF) was investigated using mandibular lymphoid tissue from normal pigs and pigs inoculated oronasally with highly virulent Lisbon 60 (L-60) and moderately virulent Dominican Republic 1979 (DR-2) ASF virus (ASFV) isolates. Paraffin-embedded tissue sections were immunostained for ASFV antigen and S-100 protein, a marker of IDCs, using an avidin-biotin alkaline phosphatase procedure. Swine IDCs were identified morphologically by light microscopy, electron microscopy, and S-100 immunostaining. Infection with ASFV caused a marked reduction in S-100 staining by 3 days postinfection (DPI) that persisted through 14 DPI. Early ASFV infection of IDCs was demonstrated at 3 DPI by double immunohistochemical staining of cryosections and by transmission electron microscopy. These results support the hypothesis that the failure of a humoral immune response to virulent ASFV may be due to a primary infection of IDCs and the inability of IDCs to initiate an immune response. Infection of IDCs has also been demonstrated with human immunodeficiency virus (HIV-1), and these infections have some aspects in common.

African Swine Fever Virus↗
PubMed1995

African swine fever interference with foot-and-mouth disease infection and seroconversion in pigs.

Initial oral infection of pigs with either highly virulent (L-60) or moderately virulent (DR-2) African swine fever virus (ASFV), followed in 3 days with exposure to foot-and-mouth disease virus (FMDV) (tongue inoculation and contact), failed to cause FMDV infection or seroconversion in 18 of 22 L-60-infected pigs and 13 of 34 DR-2-infected pigs. Of the 13 DR-2-infected pigs remaining free of foot-and-mouth disease (FMD), 2 pigs survived to 24 days without antibody to FMDV, despite constant contact with clinically infected pigs with FMD. Three other DR-2-infected pigs never developed FMD lesions but did develop low levels of antibody to FMDV by day 17. A group of larger pig (in which DR-2 is less virulent) infected with DR-2 and then FMDV had a rapid but suppressed immune response to FMDV. Contact pigs introduced 3 days postinoculation and inoculated with FMDV only all became infected with ASFV by contact and died. This remarkably long lasting 1-way interference with FMD infection during acute and subacute African swine fever was not anticipated. Infection with ASFV may have blocked the initial target cells (possibly dendritic cells) necessary for establishment of FMDV infection.

African Swine Fever↗
PubMed1995

African swine fever virus infection of skin-derived dendritic cells in vitro causes interference with subsequent foot-and-mouth disease virus infection.

Highly purified skin-derived dendritic cells (SDDCs) isolated from swine skin by a simple novel method were cultured for 24 hours before independent or sequential inoculation with African swine fever virus (ASFV) and foot-and-mouth disease virus (FMDV). By avidin-biotin immunohistochemical staining, ASFV antigen was detected in 50% of SDDCs as early as 1.5 hours postinfection (HPI) and in 80% by 3 HPI when cytopathic effect was noted. Cell lysis was detected with FMDV infection as early as 8 HPI; immunostaining for FMDV antigen was found in 10% of the cells. African swine fever virus replication was detected by transmission electron microscopy in a high percentage of SDDCs by 11 HPI. Sequential infection with FMDV 3 hours after ASFV inoculation blocked FMDV infection. These findings demonstrate that both ASFV and FMDV infect dendritic cells of Langerhans cell type in vitro and ASFV interferes with FMDV infection.

African Swine Fever Virus↗
PubMed1995

Trypanosoma cruzi infection in Walker hounds from Virginia.

Trypanosomiasis has been reported in dogs from Texas, Oklahoma, Louisiana, and South Carolina. We describe the first isolation and characterization of Trypanosoma cruzi from a Walker Hound pup in Virginia that also had postvaccinal distemper. The mother of the pup and 7 of its 8 siblings also were found to be infected with T cruzi, suggesting that the parasite had been transmitted transplacentally or through lactation. Parasitologic, serologic, histologic, and molecular methods were used to establish the diagnosis of T cruzi infection in these dogs. In a serologic survey of 12 dogs (including the sire of the pups) from the area in which the index case occurred, none were found to have antibodies to T cruzi. However, 2 of a further 52 dogs from different areas (to the index case), but in the same county, were seropositive to T cruzi. These findings indicate that canine trypanosomiasis is present in an area of the United States not previously known to be enzootic.

Animals↗
PubMed1994

XX sex reversal in a llama.

A 5-month-old llama was examined for evaluation of sexually ambiguous external genitalia. To determine the phenotypic, chromosomal, and gonadal sex of the llama, transrectal palpation and ultrasonography, contrast cystography, karyotype evaluation, laparoscopy, and necropsy were performed. A karyotype of 74,XX and finding of components of the müllerian duct system were suggestive of a female phenotype and chromosomal sex. On histologic evaluation, however, components of the wolffian duct system also were found, and the gonads were composed entirely of testicular tissue. The diagnosis was XX sex reversal, with a XX male phenotype.

Animals↗
PubMed1994

Bacterial endotoxemia and reproductive effects in ruminants.

Gram-negative bacterial infections are fairly common in domestic ruminants. They can cause an endotoxemia with a variety of systemic signs, including fever, leukopenia, and ruminal stasis. Reproductive effects of endotoxemia include alterations in the estrous cycle and inability to maintain pregnancy. Diagnosis of endotoxemia is based largely on clinical evaluation. Confirming the diagnosis of endotoxin-induced reproductive alterations also is complicated by the lag period between clinical signs and abortion or infertility.

Abortion, Veterinary↗
PubMed1994

Effect of Salmonella endotoxin administered to the pregnant sheep at 133-142 days gestation on fetal oxygenation, maternal and fetal adrenocorticotropic hormone and cortisol, and maternal plasma tumor necrosis factor alpha concentrations.

We studied the effects of maternal exposure to endotoxin on pregnancy outcome, stimulation of the hypothalamo-hypophyseal-adrenal axes (HHAA) of ewes and their fetuses, and maternal production of tumor necrosis factor alpha (TNF alpha), a central mediator in the pathogenesis of bacterial endotoxemia. Either endotoxin (lipopolysaccharide, LPS) from Salmonella typhimurium or saline was administered to pregnant sheep (n = 10) at 137.6 +/- 3.5 days gestational age by slow i.v. infusion at 1 microgram.kg-1 total dose over a 3-h period. Fetuses of ewes treated with LPS became hypoxemic by 2.5 h after initiation of LPS infusion. Maternal ACTH increased and peaked during LPS administration to levels approximately 10-fold greater in treated than in control ewes. In contrast, fetal ACTH levels were maximum at 6-12 h. Maternal and fetal cortisol levels were significantly different from control levels by 1 and 12 h, respectively. Maternal plasma TNF alpha peaked (6-7-fold over baseline) at 1-2 h after initiation of LPS administration and steadily declined over the following 48 h. Four of 5 treated ewes either delivered or their fetuses died within 28 h. In summary, infusion of LPS caused fetal hypoxemia and stimulated both fetal and maternal HHAA followed by preterm labor by 28 h after infusion in 4 of 5 ewes. Three of the fetuses died in utero. Maternal plasma TNF alpha rose rapidly, but the specific role it may play in initiation of preterm labor remains to be elucidated.

Adrenocorticotropic Hormone↗