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Biomedical subjects

D Brockman

Publications and source records attributed to D Brockman.

15 recordsLinked to original sources
PubMed2006

Nitration of p38 MAPK in the placenta: association of nitration with reduced catalytic activity of p38 MAPK in pre-eclampsia.

Peroxynitrite, a potent pro-oxidant formed from the interaction of superoxide and nitric oxide, has been widely reported to be nitrating tyrosine residues in proteins resulting in the formation of nitrotyrosine. Biological nitration of tyrosine, a footprint of oxidative injury, has been found to occur in various pathological states including pre-eclampsia, a leading cause of maternal mortality and increased perinatal mortality. Oxidative stress is a major contributor to endothelial dysfunction in pre-eclampsia. Previously, we have demonstrated increased nitrotyrosine immunostaining in placental villous vascular endothelium, surrounding vascular smooth muscle and villous stroma from pre-eclamptic or diabetic pregnancies. Immunoprecipitation (IP) with antinitrotyrosine antibodies followed by immunoblot analysis identified increased nitration of phospho-p38 mitogen-activated protein kinase (MAPK) in the pre-eclamptic placenta. The catalytic activity of p38 MAPK and concentration of phospho-p38 MAPK was also found to be reduced in placentae from pre-eclamptic pregnancies. Comparison of peptide masses of a 42-kDa protein obtained by mass spectrometry with masses of a theoretical tryptic digest of p38 MAPK that was modified by phosphorylation and nitration identified the protein to be p38 MAPK.

Adult↗
PubMed2006

Nasal oncocytoma in a domestic shorthair cat.

An oncocytoma was diagnosed in the nasal cavity of a 12-year-old Domestic Shorthair cat who presented with periocular swelling and sneezing. Histologic examination from biopsy material revealed monomorphic sheets, anastomosing cords, tubules, and acini composed of large polygonal to oval cells that contained abundant finely granular eosinophilic cytoplasm. No vascular or lymphatic invasions were noted. Histochemical stains revealed positive staining of tumor cells with periodic acid-Schiff (PAS) (before and after diastase digestion) and phosphotungstic acid-hematoxylin. Immunohistochemical evaluation of the tumor cells demonstrated positive staining for cytokeratin and negative staining for vimentin, desmin, S-100, glial fibrillar acidic protein, and neuronal specific enolase. Ultrastructurally, the tumor cells contained large numbers of mitochondria within their cytoplasm, which confirmed a diagnosis of oncocytoma.

Adenoma, Oxyphilic↗
PubMed2005

Expression of NADPH oxidase isoform 1 (Nox1) in human placenta: involvement in preeclampsia.

Increased oxidative stress in the placenta has been associated with preeclampsia (PE), a clinical syndrome involving placental pathology. The enzymatic sources of reactive oxygen species in the human placenta are as yet unidentified. We hypothesized that NADPH oxidase is a main source of reactive oxygen species in the placenta and its expression may change in PE. Employing RT-PCR, we have amplified a novel NADPH oxidase isoform Nox1 from human choriocarcinoma BeWo cells. Using polyclonal anti-peptide antiserum recognizing unique Nox1 peptide sequences, we identified by immunohistochemistry and cell fractionation that Nox1 protein localizes in the BeWo cell membrane structures. Immunohistochemistry of normal placental tissues showed that Nox1 was localized in syncytiotrophoblasts, in villous vascular endothelium, and in some stromal cells. At the immunohistochemical level Nox1 expression was significantly increased in syncytiotrophoblast and endothelial cells in placentas from patients with preeclampsia as compared to gestational age-matched controls. Western blot analysis of whole placental homogenate confirmed this increase. Our data suggests that increased Nox1 expression is associated with the increased oxidative stress found in these placentas.

Cell Line, Tumor↗
PubMed2000

Role of peroxynitrite in altered fetal-placental vascular reactivity in diabetes or preeclampsia.

Oxidative stress may increase production of superoxide and nitric oxide, leading to formation of prooxidant peroxynitrite to cause vascular dysfunction. Having found nitrotyrosine residues, a marker of peroxynitrite action, in placental vessels of preeclamptic and diabetic pregnancies, we determined whether vasoreactivity is altered in these placentas and treatment with peroxynitrite produces vascular dysfunction. The responses of diabetic, preeclamptic, and normal placentas to increasing concentrations of the vasoconstrictors U-46619 (10(-9)-10(-7) M) and ANG II (10(-9)-10(-7) M) and the vasodilators glyceryl trinitrate (10(-9)-10(-7) M) and prostacyclin (PGI(2); 10(-8)-10(-6) M) were compared as were responses to these agents in normal placentas before and after treatment with 3.16 x 10(-4) M peroxynitrite for 30 min. Responses to both vasoconstrictors and vasodilators were significantly attenuated in diabetic and preeclamptic placentas compared with controls. Similarly, responses to U-46619, nitroglycerin, and PGI(2), but not ANG II, were significantly attenuated following peroxynitrite treatment. The presence of nitrotyrosine residues confirmed peroxynitrite interaction with placental vessels. Overall, our data suggest that peroxynitrite formation is capable of attenuating vascular responses in the human placenta.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1997

Immunohistochemical localization of phospholipase A2 isoforms in human myometrium during pregnancy and parturition.

OBJECTIVE: The purpose of this study was to localize secretory phospholipase A2 and cytosolic phospholipase A2 isoforms in pregnant human myometrium and to determine changes in expression with gestational age or parturition. STUDY DESIGN: Myometrium was collected at cesarean section at term (>37 weeks) or preterm (<37 weeks) from patients who were or were not in labor (n = 5 each group). Frozen sections were incubated with specific monoclonal antibodies against secretory phospholipase A2 or cytosolic phospholipase A2 and immunostaining visualized with the Vectastain ABC method. The intensity of immunostaining in different cellular localizations was scored by an investigator blinded to tissue identity and compared among tissues with use of the Mantel-Haenszel chi2 test. RESULTS: Secretory phospholipase A2 immunostaining was dispersed in the perinuclear region throughout the myometrial smooth muscle fibers and in vascular smooth muscle. Cytosolic phospholipase A2 immunostaining was predominantly localized to endothelial cells of myometrial blood vessels and weakly throughout myometrial fibers. There was no apparent change in intensity of immunostaining for either isoform with gestational age or with the absence or presence of labor. CONCLUSION: The differential localization of the two phospholipase A2 isoforms suggests different functions. The apparent lack of change in expression during late gestation or with labor possibly suggests changes in myometrial phospholipase A2 activity and hence local myometrial arachidonic acid mobilization and presumably prostaglandin synthesis may not be associated with the onset of or maintenance of parturition.

Female↗
PubMed1997

Electromyographic data from TMD patients with myofascial pain and from matched control subjects: evidence for statistical, not clinical, significance.

This study tested the hypotheses that electromyographic (EMG) activity at rest would be significantly greater for temporomandibular disorder (TMD) patients with myofascial pain than for nonpain control subjects, and that a cutoff score based on EMG values could be established to accurately separate the two groups. Fifty-four TMD patients diagnosed with myofascial pain and 54 nonpain control subjects who were matched for age and gender were examined. Both groups participated in an EMG scanning procedure in which the left and right frontalis, temporalis, and masseter muscles were examined. Results showed that the TMD group had significantly higher EMG activity at rest for three of the six sites examined. The application of a cutoff value that produced the smallest classification error nonetheless resulted in misclassification of about one third of the TMD and nonpain individuals. These data provide little support for the use of resting EMG data obtained via a scanning procedure in accurately distinguishing facial pain patients from nonpain control subjects.

Adult↗
PubMed1994

Diagnosis and management of laryngeal disease in the dog and cat.

The larynx of the dog and cat controls the air flow to the lungs and prevents food or fluid from entering the airway during swallowing. Also, the larynx is important for vocalization and generating the explosive force necessary to expel material from the airways during the cough reflex. This article discusses the diagnosis and management of laryngeal disease in the dog and cat.

Animals↗
PubMed1986

Effect of antipyrine on prostaglandin levels and uterine and umbilical blood flow.

Antipyrine and 4-aminoantipyrine have been used for approximately 20 years to measure uterine and umbilical blood flow. Fetal infusion of 4-aminoantipyrine has been shown to decrease myometrial activity and to significantly lower prostaglandin F2 alpha metabolite levels. Since prostaglandins are thought to be important in regulating uterine and umbilical blood flow, their decrease could cause significant changes in blood flow. The purpose of the present study was to evaluate the effects of antipyrine on uterine and umbilical blood flow as measured with electromagnetic flow probes and to determine whether antipyrine causes significant changes in levels of prostaglandin E2, prostaglandin F2 alpha metabolite, and prostaglandin I2 measured as 6-keto-prostaglandin F1 alpha. Antipyrine infusion produced significant reductions in the uterine venous levels of prostaglandin E2 and prostaglandin F2 alpha metabolite (p less than 0.05). These reductions in prostaglandin levels were not associated with any significant changes in maternal blood pressure, heart rate, uterine blood flow, or oxygen content. Although fetal prostaglandin levels tended to decrease during the antipyrine infusion, these changes were not significant. Fetal blood pressure, heart rate, umbilical blood flow, PaO2, and oxygen content were not significantly altered. These data suggest that the antipyrine method does not affect basal blood flow in the uterine or umbilical circulation even though uterine prostaglandin levels are significantly decreased.

6-Ketoprostaglandin F1 alpha↗
PubMed1982

Intestinal obstruction and perforation caused by undigested Acacia sp leaves in langur monkeys.

During a 2-week period, 3 hanuman langurs (Presbytis entellus) died from severe fibrinopurulent and proliferative peritonitis. Partially digested plant material was identified in the necrotic abdominal debris of the 1st and 2nd langurs. In the 3rd, a phytobezoar that extended 17.5 cm distally from the pyloric area had caused a 1-cm perforation. Seven months later, surgery was performed on a douc langur (Pygathrix nemaeus) to remove 1 gastric and 2 intestinal phytobezoars composed primarily of undigested Acacia sp leaves. An analysis of Acacia sp leaves consumed by these langurs revealed a high cell wall concentration (40%, dry basis), with an exceedingly high proportion of this cell wall composed of indigestible lignin. It was concluded that the species of acacia (Acacia saligna and A longifolia) fed in these cases are inappropriate browse items for langurs.

Acacia↗
PubMedDate not supplied

Oxidative stress causes vascular dysfunction in the placenta.

Increased production of superoxide and nitric oxide may produce oxidative stress in the placenta by formation of the prooxidant peroxynitrite, which itself causes vascular dysfunction. Nitrotyrosine residues, which are a marker of peroxynitrite formation and action, are found in placental vessels of preeclamptic and diabetic pregnancies, indicating oxidative stress. Treatment of the placental vasculature with authentic peroxynitrite in vitro attenuates responses both to vasoconstrictors such as the thromboxane mimetic U46619 and to vasodilators, including glyceryl trinitrate and prostacyclin, indicating it has caused vascular dysfunction. Further, the responses of the fetal-placental vasculature of diabetic and preeclamptic placentae to these same vasoconstrictor and vasodilator agents are significantly attenuated when compared to responses in normal control placentae. Together these data suggest there may be a cause and effect relationship between formation and action of peroxynitrite and vascular dysfunction in the placenta of both preeclamptic and diabetic pregnancies. The presence of such attenuated vascular responses indicates that perhaps the placenta may not be able to adequately respond to demands for altered blood flow in situations where this is necessary in preeclamptic or diabetic pregnancies, thus leading to further fetal compromise.

Blood Vessels↗
PubMedDate not supplied

Determination of non-bilayer phospholipid arrangements and their antibodies in placentae and sera of patients with hypertensive disorders of pregnancy.

Studies suggest that preeclampsia (PE) originates in the placenta and is associated with deficient trophoblast invasion of spiral arteries. The direct cause remains unknown, but preeclampsia is often associated with circulating factors that can induce generalized endothelial dysfunction. Antiphospholipid antibodies (APA) in circulation are also associated with vascular diseases. Although the quantification of APA is not currently used as a prognostic of the risk of PE, studies suggest that thrombophilias play a role in PE pathogenesis. In fact, the pathology of placentae from PE and Antiphospholipid syndrome patients is similar; atherosis, thrombosis and infarction, and endothelium activation represent the pathological mechanisms. We identified a new antibody which recognizes non-bilayer phospholipid arrangements (NPA) in membrane models and in cell membranes in vivo, and which triggered an autoimmune-like disease in mice. We evaluated the presence of NPA in the placentae and in sera, and whether NPA induced NPA antibodies in patients with hypertensive disorders of pregnancy (HDP). Results showed increased levels of NPA in the syncytiotrophoblast, extravillous cytotrophoblast, syncytial knots and the amnion epithelial cell membranes of the placenta, as well as increases in NPA and NPA antibodies in sera from HDP patients, when compared with controls. This suggests that NPA derived from placenta could be one of multiple factors associated with pregnancy pathologies.

Antibodies, Antiphospholipid↗