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Biomedical subjects

A J Morris

Publications and source records attributed to A J Morris.

At least 91 records · Page 5Linked to original sources
PubMed1999

Maxillary sinusitis caused by medusoid form of Schizophyllum commune.

We present a case of maxillary sinusitis in a diabetic female caused by the basidiomycete fungus Schizophyllum commune. Identification of the isolate was hampered by its atypical features. Subcultures formed sterile medusoid structures from nonclamped mycelia until spontaneous dikaryotization resulted in the development of characteristic fan-shaped fruiting bodies. Identification was confirmed by the presence of spicules formed on the hyphae and by vegetative compatibility with known isolates.

Female↗
PubMed1999

Physiological regulation of G protein-linked signaling.

Heterotrimeric G proteins in vertebrates constitute a family molecular switches that transduce the activation of a populous group of cell-surface receptors to a group of diverse effector units. The receptors include the photopigments such as rhodopsin and prominent families such as the adrenergic, muscarinic acetylcholine, and chemokine receptors involved in regulating a broad spectrum of responses in humans. Signals from receptors are sensed by heterotrimeric G proteins and transduced to effectors such as adenylyl cyclases, phospholipases, and various ion channels. Physiological regulation of G protein-linked receptors allows for integration of signals that directly or indirectly effect the signaling from receptor-->G protein-->effector(s). Steroid hormones can regulate signaling via transcriptional control of the activities of the genes encoding members of G protein-linked pathways. Posttranscriptional mechanisms are under physiological control, altering the stability of preexisting mRNA and affording an additional level for regulation. Protein phosphorylation, protein prenylation, and proteolysis constitute major posttranslational mechanisms employed in the physiological regulation of G protein-linked signaling. Drawing upon mechanisms at all three levels, physiological regulation permits integration of demands placed on G protein-linked signaling.

Animals↗
PubMed1999

Small-bowel investigation in occult gastrointestinal bleeding.

Obscure gastrointestinal bleeding after careful endoscopy of the upper and lower gastrointestinal tract is predominantly of small-bowel origin. Patients presenting with overt blood loss account for a select subpopulation of those with small-bowel bleeding. Although relatively rare, these patients often require repeated blood transfusions, investigation, and hospitalization before a diagnosis is reached. These events have a considerable negative impact on the patient's quality of life. Standard evaluation using enteroclysis, tagged red cell studies, and angiography are proven to be of limited value in this context. Push enteroscopy has significant advantages in this patient group, with the ability to deliver endoscopic therapy. Sonde enteroscopy is now reserved for a few patients to guide decisions on surgery, particularly in those with significant medical comorbidity. Definitive evaluation may require perioperative enteroscopy, but many patients can be managed without the need for surgery. A team approach by physician, radiologist, and surgeon following locally agreed algorithms is essential for the successful management of this challenging clinical problem.

Aged↗
PubMed1999

Mainstream or sidelined? The choice for dentistry.

The 1998 white paper 'The New NHS: Modern, Dependable' announced changes to the way in which healthcare will be commissioned in the future, stimulating debate on how dentistry fits in with these developments. In this paper the authors examine first the mechanism by which healthcare is commissioned under the existing arrangements and then look at how this might develop in the future. The authors conclude that oral health will continue to be a priority for the NHS and therefore dental care will continue to be included in the portfolio of commissioned healthcare. This will however necessitate a continued dialogue between commissioners and providers and the opportunity for dental services to stay within the mainstream of the NHS by working within the new system has to be seized by the profession.

Dental Care↗
PubMed1999

Nonsteroidal anti-inflammatory drug enteropathy.

Although the upper gastrointestinal toxicity of non-steroidal anti-inflammatory drugs( NSAID) is well documented, the appreciation that NSAID damage extends beyond the duodenum is less well recognized. Recent data suggests that clinically important ulceration can be found in the small intestine, and may lead to complications such as obscure bleeding, perforation, or obstruction. Enteroscopy has identified the endoscopic and microscopic features of this condition known as NSAID enteropathy. Information supplied by enteroscopy has proven invaluable in managing patients with suspected NSAID enteropathy. This article provides an update on clinical features, endoscopic appearance, pathology, and outcome of NSAID enteropathy.

Anemia, Iron-Deficiency↗
PubMed1998

Human type 2 phosphatidic acid phosphohydrolases. Substrate specificity of the type 2a, 2b, and 2c enzymes and cell surface activity of the 2a isoform.

Phosphatidic acid (PA), lysophosphatidic acid, ceramide 1-phosphate (C1P), and sphingosine 1-phosphate (S1P) are lipid mediators generated by phospholipases, sphingomyelinases, and lipid kinases. The major pathway for degradation of these lipids is dephosphorylation catalyzed by members of two classes (types 1 and 2) of phosphohydrolase activities (PAPs). cDNAs encoding two type 2 PAPs, PAP-2a and -2b, have been expressed by transient transfection and shown to catalyze hydrolysis of PA, C1P, and S1P (Kai, M., Wada, I., Imai, S., Sakane, F. and Kanoh, H. (1997) J. Biol. Chem. 272, 24572-24578). We report the cloning and expression of a third type 2 PAP enzyme (288 amino acids, predicted molecular mass of 32.6 kDa), PAP-2c, which exhibits 54 and 43% sequence homology to PAPs 2a and 2b. Expression of HA epitope-tagged PAP-2a, -2b, and 2c in HEK293 cells produced immunoreactive proteins and increased membrane-associated PAP activity. Sf9 insect cells contain very low endogenous PAP activity. Recombinant expression of the three PAP enzymes using baculovirus vectors produces dramatic increases in membrane-associated Mg2+-independent, N-ethylmaleimide-insensitive PAP activity. Expression of PAP-2a but not PAP-2b or -2c resulted in high levels of cell surface PAP activity in intact insect cells. Kinetic analysis of PAP-2a, -2b, and -2c activity against PA, lysophosphatidic acid, C1P, and S1P presented in mixed micelles of Triton X-100 revealed differences in substrate specificity and susceptibility to inhibition by sphingosine, Zn2+, and propranol.

Amino Acid Sequence↗
PubMed1998

Association of the insulin receptor with phospholipase C-gamma (PLCgamma) in 3T3-L1 adipocytes suggests a role for PLCgamma in metabolic signaling by insulin.

Phospholipase C-gamma (PLCgamma) is the isozyme of PLC phosphorylated by multiple tyrosine kinases including epidermal growth factor, platelet-derived growth factor, nerve growth factor receptors, and nonreceptor tyrosine kinases. In this paper, we present evidence for the association of the insulin receptor (IR) with PLCgamma. Precipitation of the IR with glutathione S-transferase fusion proteins derived from PLCgamma and coimmunoprecipitation of the IR and PLCgamma were observed in 3T3-L1 adipocytes. To determine the functional significance of the interaction of PLCgamma and the IR, we used a specific inhibitor of PLC, U73122, or microinjection of SH2 domain glutathione S-transferase fusion proteins derived from PLCgamma to block insulin-stimulated GLUT4 translocation. We demonstrate inhibition of 2-deoxyglucose uptake in isolated primary rat adipocytes and 3T3-L1 adipocytes pretreated with U73122. Antilipolytic effect of insulin in 3T3-L1 adipocytes is unaffected by U73122. U73122 selectively inhibits mitogen-activated protein kinase, leaving the Akt and p70 S6 kinase pathways unperturbed. We conclude that PLCgamma is an active participant in metabolic and perhaps mitogenic signaling by the insulin receptor in 3T3-L1 adipocytes.

3T3 Cells↗
PubMed1998

Regulation of phospholipase D2: selective inhibition of mammalian phospholipase D isoenzymes by alpha- and beta-synucleins.

Two widely expressed mammalian phosphatidylcholine (PC)-specific phospholipases D (PLD), PLD1 and PLD2, have been identified. Recombinantly expressed PLD2 has high basal activity and is insensitive to GTP-binding protein activators of PLD1 [Colley, W. C., et al. (1997) Curr. Biol. 7, 191-201]. To investigate the regulation of PLD2 we isolated PLD2, from mouse brain by immunoaffinity chromatography. The native and recombinant proteins have indistinguishable properties: PLD2 is potently activated by phosphoinositides with a vicinal 4,5-phosphate pair but is not stimulated by guanosine 5'-O-(3-thio triphosphate)-activated ADP-ribosylation factor-1, Rho family GTP-binding proteins, or protein kinases C-alpha, or -beta1. We used recombinant PLD2 in a reconstitution assay to search for regulators in cell and tissue extracts. Bovine brain contains a heat-stable protein factor that inhibits PLD2 activity in vitro. This factor was purified to homogeneity and identified as a mixture of alpha- and beta-synucleins by microsequencing and Western blotting. Recombinantly expressed alpha- and beta-synucleins inhibit PLD2 activity in vitro (K0.5 10 nM). Inhibition is not overcome by the protein or lipid activators of PLD1. Synucleins have been implicated in Parkinson's and Alzheimer's diseases. Our findings suggest that inhibition of PLD2 may be a function of synucleins. Modulation of PLD2 activity by synucleins may play a role in some aspects of the pathophysiologies that characterize these neurodegenerative diseases.

Animals↗
PubMed1998

Functional association between Arf and RalA in active phospholipase D complex.

Activation of phospholipase D1 (PLD1) by Arf has been implicated in vesicle transport and membrane trafficking. PLD1 has also been shown to be associated with the small GTPase RalA, which functions downstream from Ras in a Ras-RalA GTPase cascade that facilitates intracellular signal transduction. Although PLD1 associates directly with RalA, RalA has no effect upon the activity of PLD1. However, PLD1 precipitated from cell lysates with immobilized glutathione S-transferase-RalA fusion protein is active. This suggests the presence of an additional activating factor in the active RalA-PLD1 complexes. Because Arf stimulates PLD1, we looked for the presence of Arf in the active RalA-PLD1 complexes isolated from v-Src- and v-Ras-transformed cell lysates. Low levels of Arf protein were detected in RalA-PLD1 complexes; however, if guanosine 5'-[gamma-thio]triphosphate was added to activate Arf and stimulate translocation to the membrane, high levels of Arf were precipitated by RalA from cell lysates. Interestingly, deletion of 11 amino-terminal amino acids unique to Ral GTPases, which abolished the ability of RalA to precipitate PLD activity, prevented the association between RalA and Arf. Brefeldin A, which inhibits Arf GDP-GTP exchange, inhibited PLD activity in v-Src- and v-Ras-transformed cells but not in the nontransformed cells, suggesting that the association of Arf with RalA is required for the increased PLD activity induced by v-Src and v-Ras. These data implicate Arf in the transduction of intracellular signals activated by v-Src and mediated by the Ras-RalA GTPase cascade. Because both Arf and PLD1 stimulate vesicle formation in the Golgi, these data raise the possibility that vesicle formation and trafficking may play a role in the transduction of intracellular signals.

3T3 Cells↗
PubMed1998

Relocalization of phospholipase D activity mediates membrane formation during meiosis.

Phospholipase D (PLD) enzymes catalyze the hydrolysis of phosphatidylcholine and are involved in membrane trafficking and cytoskeletal reorganization. The Saccharomyces cerevisiae SPO14 gene encodes a PLD that is essential for meiosis. We have analyzed the role of PLD in meiosis by examining two mutant proteins, one with a point mutation in a conserved residue (Spo14pK--> H) and one with an amino-terminal deletion (Spo14pDeltaN), neither of which can restore meiosis in a spo14 deletion strain. Spo14pK--> H is enzymatically inactive, indicating that PLD activity is required, whereas Spo14pDeltaN retains PLD catalytic activity in vitro, indicating that PLD activity is not sufficient for meiosis. To explore other aspects of Spo14 function, we followed the localization of the enzyme during meiosis. Spo14p is initially distributed throughout the cell, becomes concentrated at the spindle pole bodies after the meiosis I division, and at meiosis II localizes to the new spore membrane as it surrounds the nuclei and then expands to encapsulate the associated cytoplasm during the formation of spores. The catalytically inactive protein also undergoes relocalization during meiosis; however, in the absence of PLD activity, no membrane is formed. In contrast, Spo14pDeltaN does not relocalize properly, indicating that the failure of this protein to complement a spo14 mutant is due to its inability to localize its PLD activity. Furthermore, we find that Spo14p movement is correlated with phosphorylation of the protein. These experiments indicate that PLD participates in regulated membrane formation during meiosis, and that both its catalytic activity and subcellular redistribution are essential for this function.

Alkaline Phosphatase↗
PubMed1998

Hepatic blood flow changes in chronic hepatitis C measured by duplex Doppler color sonography: relationship to histological features.

Our aim was to determine if portal vein and hepatic artery blood flow indices are a noninvasive index of severity of liver disease in chronic hepatitis C. The effect of interferon-alpha treatment on liver blood flow was also studied. Liver blood flow measurements were recorded by duplex Doppler color sonography in 39 patients with chronic hepatitis C, 50 healthy controls, and a single patient with hepatocellular carcinoma. Doppler perfusion index (DPI) (calculated as the ratio of hepatic artery flow to total hepatic flow) and the congestive index of the portal vein (area/velocity) were calculated. Liver biopsies were scored for hepatic inflammation and fibrosis. Hepatic arterial flow (415.7+/-329.1 ml/min vs 195.1+/-103.5 ml/min) and DPI (0.27+/-0.14 vs. 0.17+/-0.06) were elevated in chronic hepatitis C patients compared to controls (P = 0.0002 and 0.0003, respectively) while portal vein flow and total hepatic flow were similar. Portal vein congestive index was similar in chronic hepatitis C (0.106+/-0.05) compared to controls (0.125+/-0.08) P 0.52. Hepatic blood flow indices were not related to the grade of hepatic inflammation or the stage of hepatic fibrosis. Twelve weeks of treatment with interferon-alpha had no effect on liver blood flow. In conclusion, patients with chronic hepatitis C have elevated hepatic artery blood flow. Hepatic blood flow indices have no relationship to the severity of histological liver injury in chronic hepatitis C, and these flow indices are unaffected by a 12-week course of interferon-alpha.

Adult↗
PubMed1998

Detection of decreased penicillin susceptibility in viridans group streptococci.

One hundred consecutive clinically significant viridans group streptococcal isolates had their susceptibility to penicillin determined by the penicillin E-test method. The ability of penicillin 2 and 10 unit disks and the oxacillin 1 microg disk to detect reduced penicillin susceptibility, ie; MIC > or = 0.25 microg/ml, in viridans group streptococci was determined by comparing the zone diameters against the penicillin E-test MICs. The sensitivity, specificity and predictive values of previous, existing and proposed interpretative criteria to detect decreased penicillin susceptibility were determined. Thirty-seven per cent of the isolates had reduced susceptibility to penicillin. The previous 1993 NCCLS interpretative criteria for the penicillin 10 unit disk, ie; resistant < or = 27 mm failed to detect 16 of 37 (43%) isolates with reduced penicillin susceptibility. The 1 microg oxacillin disk using existing meningococcal interpretative criteria, ie; resistant < or = 10 mm, failed to detect 11 of 37 (40%) isolates with reduced penicillin susceptibility. When the oxacillin 1 microg disk pneumococcal interpretative criteria were used, ie; resistant < or = 19 mm, all the isolates with reduced penicillin susceptibility were detected but 42 of 63 (67%) susceptible isolates were misclassified as resistant. Based on our data, we set new interpretative criteria to detect all isolates with decreased penicillin susceptibility for each of the three disks. Using our proposed zone diameters to detect decreased penicillin susceptibility of < or = 27 mm for the penicillin 2 unit disk, < or = 35 mm for the penicillin 10 unit disk, and < or = 17 mm for the oxacillin disk, 34 (54%), 44 (70%),and 21 (33%) of the 63 susceptible isolates, respectively, were misclassified as having decreased penicillin susceptibility. Our data show that the oxacillin 1 microg disk is able to detect decreased susceptibility to penicillin in viridans group streptococci with greater specificity than either penicillin 2 or 10 unit disks.

Humans↗
PubMed1998

Do in vitro susceptibility data predict the microbiologic response to amphotericin B? Results of a prospective study of patients with Candida fungemia.

Outcome for 105 patients with candidemia treated with amphotericin B was correlated with amphotericin B in vitro susceptibility results. Thirty-three patients had microbiologic failure, which was defined as persistence of Candida in the bloodstream despite > or = 3 days of amphotericin B. Amphotericin B minimum inhibitory concentrations (MICs) were determined by the National Committee for Clinical Laboratory Standards methodology. After determination of MICs, the minimal lethal concentrations (MLCs) were determined. The isolates tested yielded a narrow range of amphotericin B MICs (0.06-2 microg/mL); only 5% (5/105) exhibited MICs > or = 1 microg/mL. The MLC range, on the other hand, was significantly broader (0.125 to > 16 microg/mL); 24% (25/105) exhibited MLCs > or = 1 microg/mL. The strongest predictor for microbiologic failure was 48-h MLC (P < .001), followed by 24-h MLC (P = .03) and 48-h MIC (P = .11). A resistant break point for amphotericin B of > 1 microg/mL for MLC and > or = 1 microg/mL for MIC could be inferred from this study.

Amphotericin B↗
PubMed1998

ADP-Ribosylation factors do not activate yeast phospholipase Ds but are required for sporulation.

ADP-ribosylation factor (ARF) proteins in Saccharomyces cerevisiae are encoded by two genes, ARF1 and ARF2. The addition of the c-myc epitope at the C terminus of Arf1 resulted in a mutant (arf1-myc arf2) that supported vegetative growth and rescued cells from supersensitivity to fluoride, but homozygous diploids failed to sporulate. arf1-myc arf2 mutants completed both meiotic divisions but were unable to form spores. The SPO14 gene encodes a phospholipase D (PLD), whose activity is essential for mediating the formation of the prospore membrane, a prerequisite event for spore formation. Spo14 localized normally to the developing prospore membrane in arf1-myc arf2 mutants; however, the synthesis of the membrane was attenuated. This was not a consequence of reduced PLD catalytic activity, because the enzymatic activity of Spo14 was unaffected in meiotic arf1-myc arf2 mutants. Although potent activators of mammalian PLD1, Arf1 proteins did not influence the catalytic activities of either Spo14 or ScPld2, a second yeast PLD. These results demonstrate that ARF1 is required for sporulation, and the mitotic and meiotic functions of Arf proteins are not mediated by the activation of any known yeast PLD activities. The implications of these results are discussed with respect to current models of Arf signaling.

ADP-Ribosylation Factor 1↗