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Biomedical subjects

J M Oliver

Publications and source records attributed to J M Oliver.

At least 73 records · Page 4Linked to original sources
PubMed1992

The effects on toxicity of circadian patterning of continuous hepatic artery infusion.

Long term continuous hepatic artery infusion of FUDR was carried out in 34 rats. In the animals who received a constant infusion schedule of 15 mg/kg/day all died of toxicity with a mean survival of 9.3 days. If the pattern of the continuous infusion was changed so that over 60% of the infusion was given during the hours of 3pm to 9pm than all of the animals survived the 14 day infusion. If the maximum dose of infusion was changed so that 60% of the infusion was given at night from 3am to 9am the infusion became more toxic and all the animals died in a mean of 5.5 days. Pathologic sectioning of all the livers reflected the above outcomes with the greatest amount of hepatic necrosis in the animals on the night cycles. This study underscores the recent advances in chronobiology demonstrating that for continuous hepatic arterial infusions the timing of delivery is crucial in determining the toxicity.

Animals↗
PubMed1992

[Post-antibiotic diarrheas: role of Klebsiella oxytoca].

From May 1989 to January 1991, 20 patients were investigated for antibiotic-associated acute diarrhea. Colonoscopy or rectosigmoidoscopy was performed in each patient. Cultures of colonic mucosal biopsies were carried out using conventional culture grounds (cystine-lactose-electrolyte-deficient). The aim of this study was to investigate the role of a gram negative bacillus: Klebsiella oxytoca. Among the 20 patients with antibiotic-associated acute diarrhea, 11 had bloody and mucus diarrhea and colitis ranging from a right-sided hemorrhagic to diffuse acute ulcerative or erosive colitis, 7 had a grossly normal colonic appearance, while 2 had mucus diarrhea and pseudomembranous colitis. Of colonic biopsies cultures obtained from 36 control patients, 15 had a normal colonic appearance, 15 had ulcerative or crohn's colitis, 6 had well-tolerated amoxicillin therapy. Klebsiella oxytoca was never found in the 36 control patients; Klebsiella oxytoca was noted among 8/11 patients with mucus-discharging and bloody diarrhea. These results suggest that antibiotic-associated, non pseudomembranous colitis is frequently associated with Klebsiella oxytoca infection, which may be the cause of this type of colitis.

Adult↗
PubMed1992

[Left atrial thrombus. Its evolution with oral anticoagulation].

UNLABELLED: Left ventricular thrombi were found in 25 patients by two-dimensional echocardiography. All patients were in atrial fibrillation, 16 had mitral or mitroaortic valve diseases and nine mitral or mitroaortic bioprosthetic valves. Nine patients (36%) had history of arterial embolism. At diagnostic time, oral anticoagulation with coumadin was instaured in all the patients. Periodic clinic and echocardiography follow-up was performed. Left atrial thrombi either disappeared (18 patients [72%]) or reduced their size (one patient). Six patients with mitral stenosis were considered as candidates to percutaneous mitral valvuloplasty, which was performed in 4 patients whose thrombi disappeared with anticoagulation therapy in 6 months. During the follow-up one patient had cerebral embolism without sequelae. CONCLUSIONS: 1st. Patients with left atrial thrombi have high risk for arterial embolism. 2nd. Left atrial thrombi disappear in a high proportion after prescribing oral anticoagulation, which has some important therapeutic implications.

Administration, Oral↗
PubMed1991

Tyrosine kinase-dependent phosphatidylinostiol turnover and functional responses in the Fc epsilon R1 signalling pathway.

In RBL-2H3 rat basophilic leukemia cells, Fc epsilon R1 crosslinking by multivalent antigen stimulates phosphatidylinositol (PI) turnover and Ca2+ influx and causes functional responses that include secretion, membrane ruffling and actin polymerization. Here, we show that the tyrosine kinase inhibitor, genistein, inhibits antigen-induced PI turnover, determined from assays of 1,4,5-inositol trisphosphate production, and impairs receptor-mediated secretion, ruffling and actin polymerization. Genistein has little effect on several functional responses to stimuli that bypass PI hydrolysis (ionomycin-induced secretion, phorbol ester-induced ruffling) but it inhibits phorbol ester-induced actin polymerization. These data implicate a common tyrosine kinase-dependent event, most likely the activation of phospholipase C gamma, in the Fc epsilon R1-mediated stimulation of PI turnover, secretion and ruffling. There may be additional tyrosine kinase-mediated events in the actin assembly pathway.

Actins↗
PubMed1991

Role of isoprenoid metabolism in IgE receptor-mediated signal transduction.

In the 2H3 subline of rat basophilic leukemia cells (RBL-2H3), IgE receptor cross-linking stimulates a signal transduction pathway that leads to the secretion of histamine, serotonin, and other inflammatory mediators; the assembly of F-actin; and the transformation of the cell surface from a microvillous to a lamellar or ruffled architecture. We report here that 20 h incubation of RBL-2H3 cells with 10 microM lovastatin, an inhibitor of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMG CoA reductase), inhibits both the secretory and morphologic responses to IgE receptor cross-linking. Ag-induced Ca2+ mobilization, determined from the influx and efflux of 45Ca2+, and Ag-induced 1,4,5-inositol trisphosphate production are also inhibited in lovastatin-treated RBL-2H3 cells. Under the same conditions, lovastatin does not alter cell proliferation or IgE receptor expression, and it causes only a small impairment of responses initiated by drugs that bypass the earliest steps in the receptor-activated transduction pathway (ionomycin-induced secretion and PMA-induced membrane ruffling). Receptor-mediated Ca2+ mobilization, secretion, and ruffling are all restored by 0.5- to 4-h incubation of lovastatin-treated cells with mevalonic acid, the product of HMG CoA reductase and the first committed intermediate of the isoprenoid biosynthetic pathway. In contrast, dolichol and cholesterol, which are synthesized from products of the isoprenoid pathway, do not restore receptor-activated responses. These data implicate an isoprenoid pathway intermediate in an early step in the IgE receptor-activated signal-transduction sequence. We postulate that this intermediate is required for a newly described post-translational modification of proteins, their post-synthetic isoprenylation. The substrates for this modification include the ras family of GTP-binding proteins and the gamma subunits of the heterotrimeric guanine nucleotide-binding protein.

Animals↗
PubMed1991

Regulation of IgE receptor-mediated secretion from RBL-2H3 mast cells by GTP binding-proteins and calcium.

In RBL-2H3 rat basophilic leukemia cells, cholera toxin does not per se stimulate secretion but it enhances secretion stimulated by antigens that crosslink IgE receptors, by the Ca2+ ionophore, ionomycin, and by thapsigargin, a tumor promoter that releases cytoplasmic Ca2+ stores. Calmodulin inhibitors reduce both the basal and cholera toxin-enhanced secretory responses to antigen and Ca2(+)-mobilizing agents. These synergistic effects suggest that the activation of a Gs-like GTP-binding protein, together with a (probably calmodulin-dependent) event activated by an increase in cytoplasmic Ca2+ levels, may jointly provide a sufficient signal for secretion. Antigen-stimulated secretion is inhibited by depleting cells of GTP with mycophenolic acid but is maximal in cells treated with mycophenolic acid plus cholera toxin. The simplest explanation is that cholera toxin selectively reactivates the Gs-coupled pathway leading to secretion in GTP-depleted cells without restoring the activity of a separate GTP-binding protein(s) that constrains antigen-stimulated secretion.

Animals↗
PubMed1991

Relationship of IgE receptor topography to secretion in RBL-2H3 mast cells.

In RBL-2H3 rat leukemic mast cells, cross-linking IgE-receptor complexes with anti-IgE antibody leads to degranulation. Receptor cross-linking also stimulates the redistribution of receptors on the cell surface, a process observed here by labeling the anti-IgE with 15 nm protein A-gold particles that are visible by back-scattered electron imaging in the scanning electron microscope. We report that anti-IgE binding stimulates the redistribution of IgE-receptor complexes at 37 degrees C from a dispersed topography to distributions dominated sequentially by short chains, small clusters, and large aggregates of cross-linked receptors. Cells incubated with 1 microgram/ml anti-IgE, a concentration that stimulates maximum net secretion, redistribute receptors into chains and small clusters during a 15 min incubation period. At 3 and 10 micrograms/ml anti-IgE, net secretion is reduced and the majority of receptors redistribute rapidly into clusters and large aggregates. The addition of Fab fragments with the high anti-IgE concentrations, to reduce cross-linking, delays receptor aggregation and enhances secretion. The progression of receptors from small clusters to large aggregates is prevented in cells treated with dihydrocytochalasin B to prevent F-actin assembly. These results establish that characteristic patterns of receptor topography are correlated with receptor activity. In particular, they link the formation of large receptor aggregates to reduced signalling activity. Cytoskeleton-membrane interaction is implicated in the formation or stabilization of the large receptor clusters.

Actins↗
PubMed1991

Impaired secretion and increased insolubilization of IgE-receptor complexes in mycophenolic acid-treated (guanine nucleotide-depleted) RBL-2H3 mast cells.

In RBL-2H3 rat leukemic mast cells, cross-linking anti-DNP IgE-receptor complexes with multivalent antigen (DNP-BSA) activates a signal transduction pathway leading to Ca2+ influx and secretion. Cross-linking IgE-receptor complexes also stimulates a pathway that inactivates (desensitizes) receptors; this pathway becomes important at high concentrations of cross-linking antigen. Recent evidence that antigen-induced secretion is impaired by mycophenolic acid (MPA), an inhibitor of guanine nucleotide synthesis de novo, has implicated a GTP-binding protein (G protein) in the signaling pathway. Other recent studies have indicated that the conversion of cross-linked receptors to a detergent-insoluble (cytoskeleton-associated) form at high antigen concentrations is correlated with the loss of signaling activity. Here we show that secretion elicited by an optimal concentration of antigen (0.05 micrograms/ml DNP-BSA) is only inhibited by about 25% in guanine nucleotide-depleted cells, whereas secretion elicited by 5 micrograms/ml DNP-BSA, a concentration in the range that causes the high-dose inhibition of secretion, is inhibited by more than 60%. We also show that IgE-receptor complexes are insolubilized in response to 5 but not 0.05 micrograms/ml DNP-BSA in both control and guanine nucleotide-depleted cells. Importantly, the extent of insolubilization elicited by 5 micrograms/ml DNP-BSA is increased by more than 60% in the guanine nucleotide-depleted samples. These results raise the possibility that guanine nucleotide depletion reduces the secretory response to high antigen concentrations in two ways: by inhibiting the G protein-coupled signaling pathway and by increasing the availability of receptors to the pathway leading to receptor insolubilization and inactivation.

Animals↗
PubMed1991

Isoprenoid pathway activity is required for IgE receptor-mediated, tyrosine kinase-coupled transmembrane signaling in permeabilized RBL-2H3 rat basophilic leukemia cells.

Previously, we reported that the isoprenoid pathway inhibitor, lovastatin, blocks the activation by IgE receptor cross-linking of 45Ca2+ influx, 1,4,5-inositol trisphosphate production, secretion, and membrane changes (ruffling, spreading) in intact RBL-2H3 rat basophilic leukemia cells. These results indicated that an isoprenoid pathway intermediate, very likely an isoprenylated protein, is importantly involved in the control of IgE receptor-mediated signal transduction. Here, we show that 20 h of pretreatment with lovastatin also inhibits antigen-induced secretion and membrane responses in streptolysin O-(SLO)-permeabilized cells. However, lovastatin does not inhibit secretion stimulated by the nonhydrolyzable GTP analog, GTP gamma S. Furthermore, the membrane responses to GTP gamma S persist, although in an attenuated form, in lovastatin-treated permeabilized cells. The relative insensitivity of GTP gamma S-induced responses to lovastatin was one of several indications that antigen and GTP gamma S may activate separate pathways leading to transmembrane responses in permeabilized cells. Further experiments showed that the beta-thio derivative of GDP, GDPBAS, inhibits the secretory and membrane responses to GTP gamma S, as expected for a GTP-binding protein-dependent signaling pathway, while having little effect on antigen-induced responses. Conversely, genistein blocks the secretory and membrane responses to antigen, as expected for a tyrosine kinase-dependent pathway, without altering the GTP gamma S-induced responses. From these results, and from additional data from cells treated with tyrphostins and sodium orthovanadate, we propose that IgE receptor-mediated secretion from permeabilized RBL-2H3 cells occurs by a tyrosine kinase-dependent pathway that requires isoprenoid pathway activity for function. We propose further that RBL-2H3 cells contain a separate GTP-binding protein-mediated signaling pathway whose direct activation by GTP gamma S is either independent of isoprenoid pathway activity or depends on the activity of an isoprenylated protein that is not significantly depleted after 20 h of lovastatin treatment.

Animals↗
PubMed1990

Antigen-dependent transition of IgE to a detergent-insoluble form is associated with reduced IgE receptor-dependent secretion from RBL-2H3 mast cells.

In mast cells, basophils, and the RBL-2H3 tumor mast cell model, crosslinking cell surface IgE-receptor complexes by multivalent ligands activates a signal transduction pathway that leads to the secretion of histamine, serotonin, and other inflammatory mediators. Receptor crosslinking in RBL-2H3 cells also changes cell surface morphology and increases F-actin assembly. Previously, Robertson et al. demonstrated that crosslinked IgE-receptor complexes become associated with the Triton X-100-insoluble fraction (the "cytoskeleton") of RBL-2H3 cells and raised the possibility that receptor-cytoskeletal association may be a required step in the stimulation of secretion. The studies reported here confirm by flow cytometry that crosslinking cell surface IgE by antigen induces the association of the crosslinked complexes with the detergent-insoluble fraction. Dose-response studies, also reported here, indicate that the detergent insolubility of the complexes does not correlate with secretion. Thus, secretion increases with antigen concentration to a maximum beyond which more antigen causes less, not more, secretion. There is little residual detergent-insoluble IgE at the concentrations of antigen that promote optimal secretion, whereas the association of IgE with the detergent-insoluble fraction is maximal at the high antigen concentrations that result in reduced secretion. The addition of monovalent hapten to reduce the amount of crosslinking caused by high concentrations of antigen increases secretion and simultaneously reduces the association of IgE with the detergent-insoluble fraction. Dihydrocytochalasin B, an inhibitor of antigen-stimulated actin polymerization, also increases the rate and extent of secretion and simultaneously delays the association of crosslinked IgE-receptor complexes with the detergent-insoluble fraction. From these data, we propose that the association of crosslinked IgE receptors with the detergent-insoluble fraction of RBL-2H3 cells increases with increased receptor crosslinking, is enhanced by antigen-induced actin polymerization, and is more likely related to the termination than the stimulation of secretion. The ligand-induced conversion of receptors to a detergent-insoluble form is not restricted to mast cells but occurs in a variety of cell types. Its general function may be to limit the generation or transmission of transmembrane signals.

Animals↗
PubMed1990

[Atrioventricular block at the nodal level and block of an accessory pathway during percutaneous mitral valvuloplasty].

We describe the simultaneous occurrence of a temporal complete atrioventricular block and a persistent disappearance of preexcitation, in a patient with rheumatic mitral stenosis and a ventricular preexcitation, after an effective percutaneous mitral valvuloplasty. These conduction disturbances were attributed to atrioventricular node and paraseptal atrioventricular pathway trauma, due to transseptal manipulation during the mitral valvuloplasty.

Adult↗
PubMed1989

Depletion of guanine nucleotides with mycophenolic acid suppresses IgE receptor-mediated degranulation in rat basophilic leukemia cells.

In RBL-2H3 rat basophilic leukemia cells, Ag that crosslink IgE-receptor complexes stimulate the turnover of inositol phospholipids, the mobilization of Ca2+ from intra- and extracellular sources, the release of serotonin and other substances from granules and the transformation of the cell surface from a microvillous to a lamellar architecture. This study explores the role of GTP-binding proteins (G proteins) in the control of these biochemical and functional responses. We report that incubating RBL-2H3 cells for 4 h with 10 microM mycophenolic acid (MPA), an inhibitor of de novo GTP synthesis, reduces GTP levels by over 60% and causes an average reduction of 50% in Ag-stimulated serotonin release. This inhibition of secretion is associated with a 50% decrease in the rate of 45Ca2+ influx in MPA-treated cells. In contrast, Ag-stimulated inositol trisphosphate production is only slightly reduced, indicating that the phosphatidylinositol-specific phospholipase C can be activated by Ag in GTP-depleted cells. The membrane responses to IgE receptor cross-linking are unaffected by incubating cells with MPA. Exogenous guanine or guanosine protects the GTP pools in MPA-treated cells and permits normal ion transport and secretory responses to Ag; adenine does not. These results implicate a guanine nucleotide-binding protein in the control of IgE receptor-dependent signal transduction in RBL-2H3 cells. This protein may particularly control the Ca2+ influx pathway that is essential for secretion.

Animals↗
PubMed1989

Multiple jejunal perforations secondary to cytomegalovirus in a patient with acquired immune deficiency syndrome. Case report and review.

Disseminated cytomegalovirus infection in patients with AIDS usually involves the lungs, retina, esophagus, or colon. Gastrointestinal involvement may present clinically with fever, intractable diarrhea, and crampy abdominal pain. Ulcerations have been seen throughout the gastrointestinal tract, but perforations have been confined to the terminal ileum and colon. We report a case of a patient who presented with peritonitis with no prodromal symptoms and who, on exploration, had multiple large jejunal perforations secondary to cytomegalovirus enteropathy.

Acquired Immunodeficiency Syndrome↗
PubMed1988

The Community Placement Scale: an adaptation of the Community Competence Scale for placement of the deinstitutionalized mentally ill.

The Community Placement Scale (CPS), an abbreviated form of the Community Competence Scale (Anderten, 1979) suitable for placement of deinstitutionalized mental patients in the community, was developed in a combined sample of 87 subjects placed in the community in California and Missouri. Although the Community Competence Scale has shown considerable promise as a placement instrument with the deinstitutionalized mentally ill, a briefer measure is needed in order to increase acceptance by both patients and professional staff. Other improvements sought were determining the acceptability of items to placement personnel nationwide, eliminating nondiscriminating items, and heightening internal consistency reliability of subscales. In a series of discriminant analyses, remaining subscales were used to predict community placement with minimal and maximal degrees of structure. From these analyses, a measure that consisted of 5 subscales and 41 items and required approximately 20 minutes to administer was selected. This short form has many similarities to and a few important differences from the previously published short form.

Adult↗
PubMed1988

Immunoglobulin inclusions in Burkitt's-like malignant lymphoma: a case report.

A case of acquired immune deficiency syndrome (AIDS)-related Burkitt's-like lymphoma (BLL), demonstrating an as yet unreported occurrence of intracytoplasmic immunoglobulin inclusions, is reported. Histologic, immunocytochemical, and ultrastructural features are described with a review of the literature on signet-ring cell lymphoma.

Acquired Immunodeficiency Syndrome↗