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Biomedical subjects

K Kerr

Publications and source records attributed to K Kerr.

At least 37 records · Page 2Linked to original sources
PubMed1997

Redundant RNA recognition events in bicoid mRNA localization.

A cis-acting signal in the 3' UTR of the Drosophila bicoid mRNA directs both the transport of the mRNA from the nurse cells to the oocyte and its anterior localization within the oocyte. Here we demonstrate that the signal mediates redundant RNA recognition events, A and B, that initiate largely overlapping programs of mRNA localization during oogenesis. Recognition event A requires a region encompassing stem-loops IV/V of the predicted secondary structure, and can be eliminated by a single nucleotide mutation. Localization initiated through event B begins slightly later in oogenesis, and requires sequences that have not been narrowly defined. Using forms of the 3' UTR lacking this RNA recognition redundancy, we reexamine the roles of the swallow, staufen, and exuperantia genes, which are all required for normal bicoid mRNA localization. Our results reveal that exuperantia first becomes essential for localization at a time when well-defined microtubule tracks between the nurse cells and oocyte disappear. Thus, exuperantia may specifically facilitate a form of nurse cell-to-oocyte mRNA transport not dependent on the microtubule tracks.

Animals↗
PubMed1996

smaug protein represses translation of unlocalized nanos mRNA in the Drosophila embryo.

nanos mRNA, which encodes the localized component of the Drosophila posterior body patterning determinant, is normally translated only at the posterior pole of the embryo, where the mRNA is concentrated. Here we identify two similar cis-acting sequences in the nanos mRNA 3' untranslated region that mediate translational repression. These sequences bind an embryonic protein of 135 kD, smaug, and we refer to them as smaug recognition elements (SREs). Analysis of point mutations in the SREs reveals a strong correlation between smaug binding and translational repression; mutants unable to bind smaug in vitro are not repressed translationally in vivo, whereas mutants that do bind smaug remain repressed translationally. These results strongly suggest that smaug acts in translational repression of unlocalized nanos mRNA. Translational repression is essential, as embryos expressing a nanos mRNA with mutated SREs develop with anterior body patterning defects and die, despite correct localization of the RNA.

Animals↗
PubMed1996

Primary leiomyosarcoma of the abdominal aorta.

Primary malignancies of the aorta are extremely rare. A review of the literature indicates that 35 documented cases of primary tumors of the aorta have been reported over the past 120 years. The histologic and morphologic characteristics of these lesions may be variable. In this case, progressive claudication of the left leg and buttocks with absent femoral pulses in a middle-aged woman was found to be a primary leiomyosarcoma of the abdominal aorta. A magnetic resonance imaging study defined a retroperitoneal space-occupying mass on the left side of the aorta at the level of the fourth lumbar vertebrae. A magnetic resonance angiographic scan of the abdominal aorta and an aortogram revealed total occlusion of the distal abdominal aorta with reconstitution at the level of the common femoral arteries bilaterally, with normal vessels more distal to that region. The patient underwent surgical exploration and resection of the retroperitoneal, infrarenal, occluding aortic mass. The mass was found to be a high-grade sarcoma displaying smooth muscle cell differentiation. The resection of this lesion, perioperative management, and pathologic characteristics of a rare primary neoplasm of the aorta are discussed in this review.

Aorta, Abdominal↗
PubMed1995

Magnetic resonance angiography in the evaluation of living-related renal donors.

Live-donor kidney donation requires an accurate determination of renal arterial anatomy. Traditionally, conventional angiography has supplied this information. The present study was undertaken to determine the accuracy of magnetic resonance angiography (MRA) compared with conventional angiography (CA) in the evaluation of potential living renal donors. Fifteen potential living renal donors underwent both conventional angiography (midstream aortic injection) and three-dimensional phase contrast MRA. Two overlapping volumes of 64 slices (slice thickness 1.5 mm) were obtained in the axial plane to allow coverage from the celiac trunk to the aortic bifurcation. Conventional angiography demonstrated single renal arteries in 24 kidneys and multiple renal arteries in 6 kidneys. Magnetic resonance angiography demonstrated multiple renal arteries in 5 of the 6 kidneys. The sensitivity of MRA in determining kidneys with multiple renal arteries was 83% (5/6). One kidney with an accessory 2-mm polar artery was incorrectly identified as having a single renal artery by MRA. The overall accuracy of MRA in identifying the number of renal arteries was 97% (29/30). Fibromuscular dysplasia was demonstrated in 2 patients by CA, but was not visualized prospectively by MRA. Based on standard physician and hospital fees for each procedure, use of MRA alone would represent a cost savings of approximately $1900 over CA. Despite its minimally invasive and economic attractions, MRA does not achieve the level of accuracy required to replace CA in the evaluation of potential living kidney donors.

Female↗
PubMed1995

exl protein specifically binds BLE1, a bicoid mRNA localization element, and is required for one phase of its activity.

Localization of mRNAs, a crucial step in the early development of some animals, has been shown to be directed by cis-acting elements that presumably interact with localization factors. Here we identify a protein, exl, that binds to BLE1, an RNA localization element from the Drosophila bicoid mRNA. Using mutations in BLE1, we demonstrate a correlation between in vitro exl binding and one phase of in vivo localization directed by BLE1, implicating exl in that localization event. Furthermore, the same phase of localization is disrupted in exuperantia mutants, suggesting that exl and exuperantia proteins interact. Identification of a protein that binds specifically to an mRNA localization element and acts in mRNA localization opens the way for a biochemical analysis of this process.

Animals↗
PubMed1995

Translational regulation of oskar mRNA by bruno, an ovarian RNA-binding protein, is essential.

Oskar (osk) protein directs the deployment of nanos (nos), the posterior body-patterning morphogen in Drosophila. To avoid inappropriate activation of nos, osk activity must appear only at the posterior pole of the oocyte, where the osk mRNA becomes localized during oogenesis. Here, we show that translation of osk mRNA is, and must be, repressed prior to its localization; absence of repression allows osk protein to accumulate throughout the oocyte, specifying posterior body patterning throughout the embryo. Translational repression is mediated by an ovarian protein, bruno, that binds specifically to bruno response elements (BREs), present in multiple copies in the osk mRNA 3'UTR. Addition of BREs to a heterologous mRNA renders it sensitive to translational repression in the ovary.

Animals↗
PubMed1994

Components acting in localization of bicoid mRNA are conserved among Drosophila species.

Substantial insights into basic strategies for embryonic body patterning have been obtained from genetic analyses of Drosophila melanogaster. This knowledge has been used in evolutionary comparisons to ask if genes and functions are conserved. To begin to ask how highly conserved are the mechanisms of mRNA localization, a process crucial to Drosophila body patterning, we have focused on the localization of bcd mRNA to the anterior pole of the embryo. Here we consider two components involved in that process: the exuperantia (exu) gene, required for an early step in localization; and the cis-acting signal that directs bcd mRNA localization. First, we use the cloned D. melanogaster exu gene to identify the exu genes from Drosophila virilis and Drosophila pseudoobscura and to isolate them for comparisons at the structural and functional levels. Surprisingly, D. pseudoobscura has two closely related exu genes, while D. melanogaster and D. virilis have only one each. When expressed in D. melanogaster ovaries, the D. virilis exu gene and one of the D. pseudoobscura exu genes can substitute for the endogenous exu gene in supporting localization of bcd mRNA, demonstrating that function is conserved. Second, we reevaluate the ability of the D. pseudoobscura bcd mRNA localization signal to function in D. melanogaster. In contrast to a previous report, we find that function is retained. Thus, among these Drosophila species there is substantial conservation of components acting in mRNA localization, and presumably the mechanisms underlying this process.

Amino Acid Sequence↗
PubMed1994

Aggressive management of an epidemic of chronic pseudophakic endophthalmitis: results and literature survey.

Six cases of chronic endophthalmitis following extracapsular cataract extraction and lens implantation are reviewed. All were referred for tertiary management by one surgeon over a period of just over 2 years. In two of the cases coagulase negative staphylococci were isolated and in three Propionibacterium spp were retrieved. In the remaining case a mixed growth of coagulase negative staphylococci and Propionibacterium acnes was cultured. The surgical management, microbiological results, and eventual visual outcome are discussed. To our knowledge, this is the first documented outbreak of chronic pseudophakic endophthalmitis with commensal organisms from a single centre.

Aged↗
PubMed1993

Ozone-induced airway inflammation in human subjects as determined by airway lavage and biopsy.

Ozone (O3) is a major constituent of urban air pollution. The acute effects of the inhalation of O3 at ambient or near-ambient concentrations on bronchoalveolar lavage (BAL) end points consistent with a distal lung inflammatory response have been well documented in human subjects. Animal toxicologic studies have shown that the airway is also a major site of O3-induced injury and inflammation. To date, no studies have confirmed this finding in human subjects. Effects of O3 on the proximal airways are not adequately studied by BAL, which is primarily influenced by events occurring in the terminal bronchioles and alveoli. We hypothesized that O3 causes injury and inflammation in the airways in addition to that previously documented to occur in the distal lung. We performed isolated lavage of the left mainstem bronchus and forceps biopsy of the bronchial mucosa in a group of 14 healthy, athletic subjects 18 h after exposure to 0.20 ppm O3 for 4 h during moderate exercise in order to assess this possibility. We followed an identical protocol in a similar group of 12 subjects exposed to filtered air. The mean (SD) total cell count and the lactate dehydrogenase (LDH) concentration in the isolated airway lavage were significantly greater after O3 than after air, 13.9 (20.5) versus 4.9 (5.4) cells/ml x 10(4) and 18.9 (11.2) versus 9.6 (9.0) U/L, respectively. Morphometry (2,070 neutrophils/cm2 of tissue for O3 and 330 neutrophils/cm2 of tissue for air) demonstrated that O3 exposure induced an acute inflammatory cell influx into the airway.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

RNA regulatory element BLE1 directs the early steps of bicoid mRNA localization.

Deployment of the bicoid morphogen gradient in early Drosophila embryos requires the prelocalization of bicoid mRNA to the anterior pole of the egg. This anterior localization is mediated by a cis-acting localization signal contained within the 3' untranslated region of the bicoid mRNA. Here we use a series of bicoid transgenes carrying small deletions in the 3' untranslated region to survey for functional elements that constitute the localization signal. We identify and characterize one essential element, BLE1, which specifically directs the early steps of localization. In addition, we find that many deletions within the bicoid mRNA 3' untranslated region impair but do not prevent localization. One such deletion specifically interferes with a later step in localization. Thus the bicoid mRNA localization signal appears to consist of multiple different elements, each responsible for different steps in the localization process.

Animals↗
PubMed1990

Goblet cell carcinoid of the appendix.

We have reviewed all cases of goblet cell carcinoid in the Department of Pathology, Edinburgh University. Of the 10 cases identified, two had died as a result of the tumour. This would suggest a poorer prognosis than is generally recognized. Those patients who subsequently had progression of their disease were not predicted by histological criteria. Because of the unpredictable behaviour of these tumours we recommend that such patients should correctly be treated by a right hemicolectomy.

Adult↗
PubMed1989

DF-2 infection.

Explore the source record for details and available documents.

Adult↗
PubMed1989

Enolase exists in the fluid phase of cytoplasm in 3T3 cells.

We have investigated the intracellular distribution and mobility of the glycolytic enzyme enolase, using functional fluorescent analogs labeled with the succinimidyl esters of carboxyfluorescein (F1-enolase) and carboxytetramethylrhodamine (Rh-enolase) In contrast to aldolase, neither native enolase nor labeled enolase gelled filamentous actin (F-actin), as measured by falling-ball viscometry, indicating a lack of interaction between enolase and F-actin. Fluorescence redistribution after photo-bleaching (FRAP) measurements of the diffusion coefficient (D) of F1-enolase in aqueous solutions gave a value of D37,aq = 6.08 x 10(-7) cm2s-1, and no immobile fraction, consistent with a native molecular weight of 90,000. These values were not significantly different with Rh-enolase, or in the presence of F-actin, 2-phosphoglycerate or F-actin-aldolase gels, demonstrating that neither F1-enolase nor Rh-enolase binds to F-actin or aldolase in vitro. FRAP measurements of F1- and Rh-enolase microinjected into living Swiss 3T3 cells revealed spatial differences in the diffusion coefficient, but not the mobile fraction. In the perinuclear cytoplasm, we measured an apparent diffusion coefficient of 1.1 x 10(-7) cm2s-1, compared to 7.1 x 10(-8) cm2s-1 in the peripheral cytoplasm, with approximately 100% mobility of F1- or Rh-enolase in both regions. Imaging of cells co-injected with Rh-enolase and size-fractionated FITC-dextran (FD-90) revealed that Rh-enolase entered the nucleus, while FD-90 was excluded. Ratio imaging showed a relatively high nuclear ratio of Rh-enolase/FD-90, and a uniform cytoplasmic ratio, with no indication of increased concentration of enolase around stress fibers. These data demonstrate that Rh- and F1-enolase do not bind to F-actin in vitro, and are 100% mobile in vivo. Together with our recent finding that a significant fraction of aldolase binds to F-actin in vitro and is immobile in vivo, these data suggest a correlation between actin-binding activity and cytoplasmic mobility of glycolytic enzymes.

Animals↗