The class I couldn't take.
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Christianity↗
Biomedical subjects
R Foster
Publications and source records attributed to R Foster.
Enantiomers of flurbiprofen can distinguish key pathophysiological steps of NSAID enteropathy in the rat.
BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) cause gastrointestinal damage by a non-prostaglandin (PG) dependent "topical" action and by inhibiting cyclooxygenase. AIMS: To discriminate between these two effects by studying some key pathophysiological steps in NSAID enteropathy following administration of (R)- and (S)-flurbiprofen, the racemic mixture, and an uncoupler, dinitrophenol. METHODS: The effects of dinitrophenol, racemic, (R)-, and (S)-flurbiprofen on mitochondria were assessed in vitro and on key pathophysiological features of small intestinal damage in vivo (ultrastructure by electron microscopy, mucosal prostanoid concentrations, intestinal permeability, inflammation, and ulcer count) in rats. RESULTS: All the drugs uncoupled mitochondrial oxidative phosphorylation in vitro, caused mitochondrial damage in vivo, and increased intestinal permeability. Dinitrophenol and (R)-flurbiprofen caused no significant decreases in mucosal prostanoid concentrations (apart from a decrease in thromboxane (TX) B2 concentrations following (R)-flurbiprofen) while racemic and (S)- flurbiprofen reduced mucosal prostanoids significantly (PGE, TXB2, and 6-keto-PGF1alpha concentrations by 73-95%). Intestinal inflammation was significantly greater following administration of (S)-flurbiprofen and racemate than with dinitrophenol and (R)-flurbiprofen. No small intestinal ulcers were found following dinitrophenol or (R)-flurbiprofen while both racemic and (S)-flurbiprofen caused numerous ulcers. CONCLUSIONS: Dinitrophenol and (R)-flurbiprofen show similarities in their actions to uncouple mitochondrial oxidative phosphorylation in vitro, alter mitochondrial morphology in vivo, increase intestinal permeability, and cause mild inflammation without ulcers. Concurrent severe decreases in mucosal prostanoids seem to be the driving force for the development of severe inflammation and ulcers.
Animals↗
Adverse outcomes following endoscopic repair of a fetal cleft lip using an ovine model.
OBJECTIVE: The purpose of this study was to determine if endoscopic techniques could be used to repair an epithelialized lip cleft with accuracy and with an outcome comparable to fetuses treated through an open hysterotomy. INTERVENTIONS AND RESULTS: In contrast to previous open fetal cleft lip repairs in the same model, none of the five fetuses reported here had a good aesthetic result. Although there was no evidence of scar histologically, the edges of the lip were poorly approximated. The epithelial lining and underlying dermis of the wound margins were notably inverted. The orbicularis oris muscle, which had been reapproximated, appeared thin and hypoplastic. Most of the vermilion elements were poorly aligned, and in one animal, there was a complete dehiscence of the repair. CONCLUSIONS: In a more representative model of cleft lip that is not an acute lip wound, in utero endoscopic suture repair of the ovine lip gave a poor result using current technology. Only a meticulously performed, multilayered, open repair of a cleft appears to give a good cosmetic and functional outcome. Further studies to improve the endoscopic repair as our technology advances are therefore warranted.
Animals↗
Abscisic acid signaling through cyclic ADP-ribose in plants.
Abscisic acid (ABA) is the primary hormone that mediates plant responses to stresses such as cold, drought, and salinity. Single-cell microinjection experiments in tomato were used to identify possible intermediates involved in ABA signal transduction. Cyclic ADP-ribose (cADPR) was identified as a signaling molecule in the ABA response and was shown to exert its effects by way of calcium. Bioassay experiments showed that the amounts of cADPR in Arabidopsis thaliana plants increased in response to ABA treatment and before ABA-induced gene expression.
Abscisic Acid↗
Signaling functions of the tyrosine residues in the betac chain of the granulocyte-macrophage colony-stimulating factor receptor.
The granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor (GMR) is a heterodimeric receptor expressed by myeloid lineage cells. Binding of GM-CSF activates at least one receptor-associated tyrosine kinase, JAK2, and rapidly induces tyrosine phosphorylation of the GMR betac-chain (GMRbeta), but not the GMR alpha-chain (GMRalpha). To examine the role of GMRbeta tyrosine phosphorylaiton, each of the 8 tyrosine residues in the cytoplasmic domain of the human GMRbeta was mutated to phenylalanine (GMRbeta-F8), and this mutant receptor was expressed with wild-type GMRalpha in the interleukin-3-dependent murine hematopoietic cell line, Ba/F3. GM-CSF induced tyrosine phosphorylation of multiple cellular proteins in cells expressing GMRbeta-F8 , including JAK2 and STAT5. However, GM-CSF-induced tyrosine phosphorylation of both SHP2 and SHC was reduced or absent compared with wild-type. Next, a series of 8 receptors were generated, each containing only a single, restored, tyrosine residue. Tyrosine 577 was found to be sufficient to regenerate GM-CSF-dependent phosphorylation of SHC, and any of Y577, Y612, or Y695 was sufficient to regenerate GM-CSF-inducible phosphorylation of SHP2. Despite the signaling defect to SHC and SHP2, Ba/F3 cells expressing GMRbeta-F8 were still able to proliferate in response to 10 ng/mL of human GM-CSF, although mitogenesis was impaired compared with wild-type GMRbeta, and this effect was even more prominent at lower concentrations of GM-CSF (1 ng/mL). Overall, these results indicate that GMRbeta tyrosine residues are not necessary for activation of the JAK/STAT pathway or for proliferation, viability, or adhesion signaling in Ba/F3 cells, although tyrosine residues significantly affect the magnitude of the response. However, specific tyrosine residues are needed for activation of SHC and SHP2.
Animals↗
Australian bat lyssavirus infection in three fruit bats from north Queensland.
We report the case findings of Australian bat lyssavirus infection in two black flying foxes (Pteropus alecto) and one little red flying fox (Pteropus scapulatus) from north Queensland between January 1995 and August 1996. Although the P. alecto case in January 1995 is the first recognised case of Australian bat lyssavirus infection in Australia, this was a retrospective diagnosis made after identification of the index case at Ballina in May 1996. Eight persons had exposure to the three bats. Serum antibodies to classical rabies virus were measured in six of these persons; the only one seropositive was a veterinarian who had previously been vaccinated against rabies. Six persons received rabies vaccine following exposure. None of the in-contact humans developed signs of lyssavirus infection. For people exposed to Australian bat lyssavirus-positive bats who have not been scratched or bitten or had mucosal contamination by these bats, we suggest a post-exposure regime of five inoculations of the human diploid cell inactivated rabies vaccine.
Animals↗
A new in utero model for lateral facial clefts.
The etiopathogenesis behind the formation of atypical craniofacial facial clefts remains unknown. To test the hypothesis that physical restricting forces such as amniotic bands can lead to the formation of these unusual clefts in the postorganogenesis period, we have modified a previously reported fetal lamb model of amniotic band syndrome to examine the effects of these bands on craniofacial development. Five 70-day gestation fetal lambs (term, 140 days) were exposed via a maternal hysterotomy. In each animal, an attempt was made to create a lateral craniofacial cleft by applying a 2-0 nylon suture as a constriction band to the growing face. The sutures were attached to either the zygomatic arch or the infraorbital rim externally and then looped circumferentially into the oral commissure. Each suture was positioned so as to create either a Tessier type 5 or a Tessier type 7 cleft. Four of five fetal lambs survived to term. Both types of lateral facial clefts were effectively produced using this model. In each group, the presence of an intraoral constriction band led to the formation of macrostomia, with an average 7.4-mm lateral displacement of the oral commissure. In addition to these soft tissue changes, each animal also had partial bony clefting (i.e., a bony groove) induced by the pressure of the restriction band across the growing facial skeleton. In the two lambs with the Tessier type 7 cleft, incomplete bony clefts developed across the zygomatic arch. In three animals with bands placed across the medial infraorbital rim, significant infraorbital and malar bony clefts formed similar to a classic Tessier type 5 facial cleft. No evidence of tissue necrosis, maceration, or ulceration was noted in any animal. These data present, for the first time, evidence that the constriction of craniofacial growth by external forces such as a swallowed amnionic band can lead to the development of lateral facial clefting involving both soft tissue and bony elements. These malformations are likely due to a combination of directly tethering normal tissue migration and an increase in local pressure, which produces cellular ischemia and apoptosis. Furthermore, our data demonstrate that these clefts can occur later in fetal development during a period of facial growth rather than during the period of primary facial morphogenesis.
Amniotic Band Syndrome↗
Breast cancer surgical practice guidelines. Society of Surgical Oncology practice guidelines.
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Breast Neoplasms↗
Identification of a novel human Rho protein with unusual properties: GTPase deficiency and in vivo farnesylation.
We have identified a human Rho protein, RhoE, which has unusual structural and biochemical properties that suggest a novel mechanism of regulation. Within a region that is highly conserved among small GTPases, RhoE contains amino acid differences specifically at three positions that confer oncogenicity to Ras (12, 59, and 61). As predicted by these substitutions, which impair GTP hydrolysis in Ras, RhoE binds GTP but lacks intrinsic GTPase activity and is resistant to Rho-specific GTPase-activating proteins. Replacing all three positions in RhoE with conventional amino acids completely restores GTPase activity. In vivo, RhoE is found exclusively in the GTP-bound form, suggesting that unlike previously characterized small GTPases, RhoE may be normally maintained in an activated state. Thus, amino acid changes in Ras that are selected during tumorigenesis have evolved naturally in this Rho protein and have similar consequences for catalytic function. All previously described Rho family proteins are modified by geranylgeranylation, a lipid attachment required for proper membrane localization. In contrast, the carboxy-terminal sequence of RhoE predicts that, like Ras proteins, RhoE is normally farnesylated. Indeed, we have found that RhoE in farnesylated in vivo and that this modification is required for association with the plasma membrane and with an unidentified cellular structure that may play a role in adhesion. Thus, two unusual structural features of this novel Rho protein suggest a striking evolutionary divergence from the Rho family of GTPases.
Amino Acid Sequence↗
Enhanced intracoronary thrombolysis with urokinase using a novel, local drug delivery system. In vitro, in vivo, and clinical studies.
BACKGROUND: Current pharmacological regimens for treating intracoronary thrombus in the cardiac catheterization laboratory generally involve the administration of thrombolytic agents that result in a systemic fibrinolytic state and/or require prolonged arterial drug infusion. The purpose of the present study was to assess a new technique for treating intracoronary thrombus consisting of the local infusion of limited quantities of urokinase with a novel drug delivery device. METHODS AND RESULTS: THe Dispatch coronary infusion catheter is a new local drug delivery system that allows for the prolonged infusion of therapeutic agents at an angioplasty site while distal coronary flow is maintained. Three experimental protocols were performed to determine the in vitro, in vivo, and clinical efficacy of this device. First, in vitro thrombolysis of fresh, porcine thrombus trapped in a 4-mm plastic tube with a 50% constriction and perfused with 20% porcine plasma was measured. Twenty-three thrombi were weighed before and after no treatment (n = 5), "systemic" urokinase administration (n = 4), local infusion of 150,000 U urokinase with a standard end-hole catheter (n = 4), local infusion of saline with the Dispatch catheter (n = 5), and local infusion of 150,000 U urokinase with the Dispatch catheter (n = 5). Second, 25 porcine coronary arteries in 23 pigs were dilated in vivo with conventional balloon angioplasty and then treated with 123I-labeled urokinase that was administered either by the Dispatch catheter (150,000 U; n = 16), intravenous systemic bolus (1,000,000 U; n = 3), guiding catheter infusion (500,000 U; n = 3), or local end-hole catheter infusion (150,000 U; n = 3). All vessels were subsequently harvested to quantify intramural deposition and subsequent washout of urokinase at the angioplasty site. Finally, 19 patients with angiographic evidence of intracoronary thrombus were treated with local urokinase infusion with the Dispatch catheter either before or after balloon angioplasty or directional atherectomy. In vitro studies demonstrated that infusion of urokinase with the Dispatch catheter decreased thrombus weight by 66% compared with no treatment (-25%), "systemic" urokinase administration (25%), end-hole catheter urokinase infusion (32%), or infusion of saline by the Dispatch catheter (32%) (P < or = .005). In vivo studies demonstrated immediate deposition of 0.12% of the urokinase delivered by the Dispatch catheter to the angioplasty site, compared with 0.0007% with systemic bolus, 0.003% with guiding catheter infusion, and 0.007% with local infusion with an end-hole catheter (P < .001). Urokinase deposited by the Dispatch catheter persisted intramurally for at least 5 hours. Patient studies demonstrated reduction of thrombus-containing stenoses and complete disappearance of intracoronary thrombus in all cases in which 150,000 U urokinase was locally infused over 30 minutes. There was no evidence of abrupt closure, distal embolization, or no reflow in any patient. CONCLUSIONS: Local urokinase delivery with the Dispatch catheter can result in rapid and complete intracoronary thrombolysis using substantially less drug than standard thrombolytic techniques. Intramural deposition of drug with this technique creates a local reservoir of urokinase that may provide prolonged thrombolytic activity at the infusion site.
Adult↗
Purification and GTPase-activating protein activity of baculovirus expressed p190.
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Animals↗
Defining new standards for adjuvant therapy of testis cancer.
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Antineoplastic Combined Chemotherapy Protocols↗
Neovascularization in clinical stage A testicular germ cell tumor: prediction of metastatic disease.
Increased numbers of blood vessels (angiogenesis or neovascularization) in certain primary tumors correlates with an increased risk for metastatic disease. We therefore conducted a blinded review of the resected testicular germ cell tumors of 65 clinical stage A patients to evaluate the usefulness of angiogenesis in identifying those patients with clinically occult nodal metastases (pathological stage B). Angiogenesis was assessed in the primary tumors using an immunohistochemical stain for factor VIII-related antigen assay for quantitation of microvessel counts. Of 65 clinical stage A patients, 43 had pathological stage B disease at retroperitoneal lymph node dissection. Eleven patients had microvessel counts > 30 microvessels/x 400 high powered field, and all of these patients had pathological stage B disease (P = 0.02 in univariate analysis). Multiple regression analysis using microvessel count and other histological findings found to be prognostic (venous invasion, lymphatic invasion, presence of embryonal carcinoma, and absence of yolk sac tumor) showed that only the absence of a yolk sac tumor component was significantly predictive of occult metastases. This study shows that angiogenesis, as measured by quantitation of microvessel counts in the primary tumor of germ cell neoplasms, is significantly predictive of occult nodal metastatic disease by univariate analysis in clinical stage A patients. The prospective use of angiogenesis quantitation needs to be defined.
Germinoma↗
A comparison of six different plating media used in the isolation of Salmonella.
Seventeen Canadian Federal, Provincial and Public Health Laboratories took part in different phases of a comparative/collaborative study that evaluated rapid methods to the standard Health Protection Branch (HPB) method for the detection of Salmonella. A variety of commercial media were tested, including Brilliant Green Sulpha Agar, Bismuth Sulphite Agar, Hektoen Enteric Agar, Xylose Lysine Deoxycholate Agar, EF-18 Agar and Rambach Agar. Each laboratory compared up to six of these different plating media. Plating of 123 salmonellae cultures and 28 artificially-inoculated foods showed the recovery of Salmonella spp. on the six plating media to be within one log. Therefore, quantitative testing of the media showed them to be comparable in the recovery of salmonellae. Qualitative testing of the six media during the comparative/collaborative study of various methods showed that EF-18 Agar recovered the greatest number of isolates. Hektoen Enteric Agar ranked second, with the other agars being comparable in their recovery of Salmonella spp. Problems with the various media are summarized. Based on our results and those of other researchers, it is recommended that Bismuth Sulphite Agar be compulsory and that at least one other agar be used for newly developed cultural procedures.
Bacteriological Techniques↗
Ureaplasma diversum as a cause of reproductive disease in cattle.
This article includes a brief review of the classification, habitat, and characteristics of the ureaplasmas, followed by a discussion of the pathogenesis, transmission, clinical syndromes, diagnosis, immunity, and treatment of Ureaplasma diversum infections in cattle.
Abortion, Veterinary↗
Body composition in immature rats with D-galactosamine induced hepatitis and bile duct ligation.
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Animals↗
Plant bZIP proteins gather at ACGT elements.
ACGT cis-acting DNA sequence elements have been identified in a multitude of plant genes regulated by diverse environmental, physiological, and environmental cues. In vivo transient and transgenic plant expression studies have shown that these ACGT elements are necessary for maximal transcriptional activation. Plants possess a conserved family of DNA-binding proteins specific for these DNA sequence motifs. Well-defined in terms of nucleotide sequence required for protein/DNA interactions and transcriptional activation, various ACGT elements have been used as molecular probes to clone sequence-specific DNA binding proteins. All plant DNA-binding proteins specific for ACGT elements belong to the bZIP classification. Most recombinant bZIP proteins can interact with ACGT elements derived from different plant genes, albeit with different affinity. Systematic protein/DNA binding studies have shown that sequences flanking the ACGT core affect bZIP protein binding specificity. These studies have provided the basis for a concise ACGT nomenclature and defined high-affinity A-box, C-box, and G-box elements. Plant bZIP factors can be classified according to their quantitative binding affinities for high-affinity ACGT elements. Potential molecular mechanisms that may control how plant bZIP proteins activate plant gene expression are discussed.
Amino Acid Sequence↗
The rice bZIP transcriptional activator RITA-1 is highly expressed during seed development.
Systematic protein-DNA binding studies have shown that plant basic leucine zipper (bZIP) proteins exhibit a differential binding specificity for ACGT motifs. Here, we show that the rice transcription activator-1 (RITA-1) displays a broad binding specificity for palindromic ACGT elements, being able to bind A-, C-, and G-box but not T-box elements. By using gel mobility shift assays with probes differing in sequences flanking the hexameric core, we identified high-affinity A-, C-, and G-box binding sites. Quantitative and competition DNA binding studies confirmed RITA-1 specificity for these sites. Using rice protoplasts as a transient expression system, we demonstrated that RITA-1 can transactivate reporter genes possessing high-affinity but not low-affinity RITA-1 binding sites. Our results established a direct relationship between in vivo transactivation and in vitro binding activity. Transient expression assays that demonstrated the ability of RITA-1 to transactivate a construct containing rita-1 5' flanking sequences suggest that the factor may be autoregulated. Histochemical analysis of transgenic rice plants showed that a rita-1-beta-glucuronidase transgene is expressed in aleurone and endosperm cells of developing rice seeds. We propose that RITA-1 plays a role in the regulation of rice genes expressed in developing rice seeds.
Amino Acid Sequence↗