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Biomedical subjects

R O'Reilly

Publications and source records attributed to R O'Reilly.

At least 19 recordsLinked to original sources
PubMed1992

Relationships between the surface exposure of acidic phospholipids and cell fusion in erythrocytes subjected to electrical breakdown.

The procoagulant activity of human erythrocytes, which provides a measure of the translocation of acidic phospholipids from the inner to the outer monolayer of the plasma membrane, has been compared with the percentage cell fusion in experiments on the effects of electrical breakdown pulses under differing experimental conditions. After treatment with breakdown pulses of 20 microseconds or longer (5 kV cm-1), the plasma membranes of erythrocytes in 250 mM sucrose exhibited an almost complete loss of asymmetry with respect to acidic phospholipids. As the breakdown voltage was increased from 2 to 5 kV cm-1 (with breakdown pulses of 99 microseconds), the surface exposure of acidic phospholipids and cell fusion increased approximately in parallel. Furthermore, with 99 microseconds pulses and a voltage of 3 kV cm-1, a decrease in the osmolarity from 250 to 150 mM of the sucrose medium was accompanied by an increase in both the surface exposure of acidic phospholipids and the extent of cell fusion. Breakdown pulses of 2-5 microseconds were sufficient to cause a marked loss of asymmetry, but no cell fusion was observed unless the pulse length was at least 20 microseconds. Kinetic experiments indicated that exposure of the acidic phospholipids at the cell surface was more likely to be due to a direct effect of the electric field pulses on plasma membrane structure than to secondary effects, such as the action of endogenous proteinases on the membrane skeleton. It seems possible that a localised, surface exposure of acidic phospholipids may contribute to the 'long-lived fusogenic state' (Sowers, A.E. (1986) J. Cell Biol. 102, 1358-1362) and the 'transient permeant structures' (Teissié, J. and Rols, M.P. (1986) Biochem. Biophys. Res. Commun. 140, 258-266) that enable cell fusion to occur when contact between cells is established after they have been subjected to field pulses. Our observations also provide circumstantial support for the concept that changes in the phospholipid asymmetry of membranes may be important in physiologically-occurring instances of biomembrane fusion.

Animals↗
PubMed1992

Reasons that patients with acute myelogenous leukemia do not undergo allogeneic bone marrow transplantation.

BACKGROUND: Numerous reports suggest that allogeneic bone marrow transplantation prolongs the survival of adult patients with acute myelogenous leukemia (AML) in first remission. However, it is unclear how many such patients actually undergo this procedure. METHODS: We reviewed the case records of 350 consecutive adult patients with AML treated with chemotherapy at a single institution from 1979 (when the policy of offering allogeneic transplantation to all such patients in first remission was introduced) through 1990. The criteria for exclusion before transplantation included age greater than 40 and, beginning in 1984, a diagnosis of acute promyelocytic leukemia. RESULTS: One hundred forty-two patients (41 percent of the study population) were 40 years of age or under. HLA testing was performed for 120 of these patients (85 percent). Sixty-seven patients (47 percent) had an HLA-identical sibling as a potential donor. One hundred three patients (73 percent) entered remission during treatment according to one of five chemotherapy protocols. Of the 52 patients who both entered remission and had an HLA match, 30 underwent transplantation while they were in first remission. These 30 patients constituted 21 percent of all study patients 40 years old or under, 29 percent of all patients 40 or under who entered remission, 45 percent of all patients with an HLA match, 58 percent of all patients who had both a remission and a match, and 9 percent of all patients treated according to a protocol. Among patients with a match who did not undergo transplantation, those with primary refractory disease were the largest subgroup. CONCLUSIONS: These findings suggest that allogeneic bone marrow transplantation is performed in less than 60 percent of adult patients with AML who are potentially eligible for the procedure.

Adult↗
PubMed1991

Lipid peroxidation in electroporated hepatocytes occurs much more readily than does hydroxyl-radical formation.

1. Rat hepatocytes suspended in 0.25 M-sucrose were electropermeabilized. This completely disrupted their plasma-membrane permeability barrier. 2. The endoplasmic reticulum in electroporated hepatocytes appeared morphologically preserved and maintained its permeability barrier as evidenced by electron-microscopic examination and latency measurements on luminal reticular enzymes. 3. Upon aerobic incubation with an NADPH-generating system and iron/ADP, porated hepatocytes peroxidized their membrane lipids at rates similar to those of matched microsomal preparations. 4. When hepatocytes were incubated with iron/EDTA and azide, radical formation detectable with dimethyl sulphoxide (DMSO) was only 10-20% that shown by microsomes. Omitting azide abolished hepatocyte reactivity with DMSO completely. Effects of hydroxyl-radical (.OH) scavengers and of added catalase suggest that the radical detected by DMSO is .OH. 5. Cytosolic inhibitor(s) from hepatocytes seemed to be a major factor limiting .OH formation. These were macromolecular, but showed a degree of heat-stability. Dialysis largely abolished inhibition, but this could be restored again by adding GSH. 6. Since .OH formation in hepatocytes seems to be much more stringently prevented than lipid peroxidation, free-radical damage originating from intracellular redox systems seems more likely to take the form of lipid peroxidation.

Animals↗
PubMed1991

Plasma phenylethylamine in schizophrenic patients.

Plasma samples were collected from 41 patients who met DSM-III criteria for schizophrenia and from 34 healthy controls. Phenylethylamine (PE) levels were determined using a gas chromatography-mass spectrometry negative chemical ionization method. PE was significantly higher in the schizophrenic patients compared with controls. There were no differences in PE between paranoid and nonparanoid patients. Plasma PE did not appear to be influenced by the severity of schizophrenic symptoms (rated by BPRS, SANS, and SAPS) or by the amount of dietary phenylalanine ingested within 24 hr of testing. Plasma PE did not correlate with current or past exposure to neuroleptic medication. It was not possible, however, to test individual patients during two periods when they were taking and not taking medication. Thus it is possible that neuroleptic exposure may have confounded the results. This study provides further evidence that PE excess may play a role in the etiology of schizophrenia but does not support previous studies which suggest that such an abnormality is limited to the paranoid subgroup.

Adult↗
PubMed1991

No retroviremia or pathology in long-term follow-up of monkeys exposed to a murine amphotropic retrovirus.

Four monkeys were exposed to a retroviral vector and replication-competent murine amphotropic retrovirus in a bone marrow transplantation/gene transfer protocol (Kantoff et al., 1987). We have studied these animals 2 and 3 years post-transplantation and did not detect replicating virus in serum, peripheral blood mononuclear cells, or bone marrow cells. Amphotropic envelope sequences could not be detected in blood or bone marrow cells by Southern blotting or the polymerase chain reaction. Antibodies directed against the p30 and gp70 viral antigens were detected by Western blot and immunoprecipitation. The animals remain alive and well. Our findings suggest that primates can clear murine amphotropic retroviruses even when exposure occurs during a time of severe immunosuppression.

Adenosine Deaminase↗
PubMed1991

How psychiatrists weigh risk factors when assessing suicide risk.

The clinical assessment of suicide risk is a difficult task that the traditional literature contributes to in a limited way. This study aims to complement the traditional literature by determining the ranking of suicide risk factors by a group of 81 psychiatrists. Hopelessness was ranked the most important risk factor, followed by Suicidal Ideation, Previous Attempts, the Level of Mood and Affect, Quality of Relationships, Signs and Symptoms of Depression, and Social Integration. Less highly ranked risk factors are also noted. The significance of these findings is discussed with respect to the literature and commonly used textbooks of psychiatry.

Attitude of Health Personnel↗
PubMed1990

Surface exposure of phosphatidylserine is associated with the swelling and osmotically-induced fusion of human erythrocytes in the presence of Ca2+.

An assay for procoagulant activity has been used to investigate the Ca2(+)-dependent exposure of phosphatidylserine at the surface of human erythrocytes that were induced to swell and to fuse osmotically. Since the phosphatidylserine of human erythrocytes is located in the inner leaflet of the plasma membrane, it is inaccessible in intact cells which therefore had no procoagulant activity in an isotonic solution of sucrose. The procoagulant activity of erythrocytes incubated in increasingly hypotonic, sucrose solutions containing Mg2+ paralleled the percentage haemolysis, reflecting the accessibility of phosphatidylserine in an increasing number of lysed cells. However, cells in mildly hypotonic sucrose solutions containing Ca2+ had an abnormally high procoagulant activity indicating that phosphatidylserine was exposed in intact cells under these conditions. Erythrocytes that were subjected to continuous swelling at 37 degrees C, which was induced by entry of the permeant molecule poly(ethylene glycol) 400 (PEG 400) developed procoagulant activity in the presence of Ca2+ prior to extensive lysis. Cells treated in this way also fused. With Mg2+, PEG 400-treated erythrocytes lysed without fusing, and the development of procoagulant activity paralleled the rate of lysis. Erythrocytes incubated with ionophore A23187, subtilisin, and Ca2+ developed procoagulant activity (with less than 20% lysis), and they fused on subsequent exposure to a hypotonic medium. The procoagulant activity reached its maximum before fusion could be induced in the hypotonic medium. It is concluded that the entry of Ca2+ facilitates a translocation of phosphatidylserine to the outer leaflet of the erythrocyte plasma membrane that plays an important role in fusion protocols that involve cell swelling. It is also suggested that transbilayer movements of phosphatidylserine could be an important control factor in the cell biology of membrane fusion phenomena.

Biological Transport↗
PubMed1990

The use of sedative-hypnotic drugs in a university teaching hospital.

We reviewed the charts of 476 patients admitted to a university teaching hospital to determine whether sedative-hypnotic drugs (SHDs) were being used excessively and to examine the use of SHDs as hypnotics. The frequency of medical and surgical indications for barbiturates and benzodiazepines or other minor tranquillizers as well as the use of such drugs were compared among different groups of patients and specialty wards. Of the patients 29% had a regular order and 40% had a PRN order; only 77% of the PRN orders were administered. A total of 215 patients (45%) received an SHD during their hospital stay, and 160 (34%) received the drug as a hypnotic. Medical indications accounted for 49% of the regular orders but only 2% of the PRN orders; moreover, 89% of all the PRN orders were for insomnia. On average, patients receiving SHDs as hypnotics were older (p less than 0.05) and stayed longer in hospital (p less than 0.01) than those who did not; however, no patient on the geriatric or pediatric ward received an SHD as a hypnotic during the hospital stay. The differences in use between patient groups may have been influenced by orientation of ward staff. Physicians should review their rationale for prescribing hypnotics and avoid routine orders on admission.

Adult↗
PubMed1990

Both ongoing suppression and clonal elimination contribute to graft-host tolerance after transplantation of HLA mismatched T cell-depleted marrow for severe combined immunodeficiency.

Lymphocytes from children with severe combined immunodeficiency who had been immunologically reconstituted with haploidentical T cell-depleted bone marrow were analyzed with regard to their immunologic recognition of donor, host, or third party alloantigens. When compared with freshly isolated donor lymphocytes, the engrafted donor cells exhibited markedly reduced to absent responses toward host Ag in primary or secondary MLC and cell-mediated lympholysis assays. However, under limiting dilution conditions, cytotoxic responses to host Ag could be demonstrated, indicating that small numbers of host reactive cells were present, although down-regulated at high responder cell doses. These results are consistent with prior observations in limiting dilution cultures that indicate that cells with the potential to lyse autologous target cells exist in the peripheral blood of all normal individuals. The number of host reactive cells present in these patients is significantly less than that present in cells isolated directly from the marrow donors, and is also less than the number of autocytotoxic cells normally seen in peripheral blood. Together, these observations indicate that two mechanisms contribute to donor host tolerance in these patients. The majority of host reactive cells appear to have undergone clonal deletion or inactivation, whereas the small residual host-reactive population appears to be under ongoing immunoregulatory control.

Bone Marrow Transplantation↗
PubMed1989

Correlation between interleukin-1 production and engraftment of transplanted bone marrow stem cells in patients with lethal immunodeficiencies.

Interleukin-1 (IL-1) production by endotoxin-stimulated, cultured monocytes from 19 patients with lethal congenital immune disorders were studied and compared with normal controls. Lipopolysaccharide (LPS) stimulated IL-1 production was normal in three of three patients with Wiskott Aldrich syndrome (WAS), two of three combined immunodeficiency with T-cell predominance (CIDTP) and nine of 13 with severe combined immunodeficiency (SCID). Monocytes deficient in IL-1 production could be restored to normal production after incubation with indomethacin in three of five deficient patients. Monocytes from the other two patients could not be induced to generate IL-1, suggesting either an intrinsic deficiency or an alternate inhibitory mechanism as the basis for the IL-1 deficiency observed. In patients with SCID who were transplanted with HLA-haplotype disparate, T-cell depleted marrow without preparative chemotherapy, deficiency of monocyte IL-1 production was correlated with graft failure. Immune reconstitution was achieved in IL-1 deficient patients only when donor monocytes were also engrafted. We hypothesize that deficiencies of IL-1 production may contribute to the heterogeneous expression of combined immunodeficiencies, and may also restrict the engraftment and functional development of allogeneic lymphoid progenitors from a T-cell depleted marrow graft.

Bone Marrow Transplantation↗
PubMed1989

Bare lymphocyte syndrome: altered HLA class II expression in B cell lines derived from two patients.

Types II and III bare lymphocyte syndrome (BLS) are severe or lethal congenital immunodeficiencies characterized by defective cell surface expression of HLA class II antigens. We have analyzed by Southern and Northern blotting B-lymphoblastoid cell lines derived by Epstein-Barr virus (EBV) transformation from peripheral blood lymphocytes of two unrelated BLS patients and their families. While DNA analyses of both families showed no indication of rearrangement or alteration of HLA region genes, class II mRNAs were virtually absent in the patients' cell lines (BLS-1 and BLS-2). This is consistent with previous observations of different BLS patients and their families. An exception to the absence of class II mRNAs in BLS was the detection of low quantities of HLA-DQ alpha transcripts in the cell lines BLS-1. This finding provides further evidence that factors regulating HLA-DQ expression may differ from those governing expression of the other class II genes.

B-Lymphocytes↗
PubMed1989

A performance appraisal system for quality assurance and utilization review fellows.

There is now increased interest in developing continuing education and career training programs in quality assurance and utilization review. These programs frequently involve on-site practicum experiences for which the performance appraisal system described here was developed. Incorporating a new evaluation technology known as the rating grid, this system is discussed here in terms of its underlying rationale, its rating factors, and the observation and scoring factors used by the observer-evaluator. The system can be used by observers to give feedback to physicians and others undergoing training in quality assurance and utilization review.

Clinical Competence↗
PubMed1987

The transfer syndrome.

Both patients and psychiatric residents are seen to exhibit symptoms as the end of the resident's job rotation approaches and the need arises to transfer the patient's care to a new therapist. These symptoms, collectively known as the "Transfer Syndrome", are examined. An approach to modify these problems is outlined. Finally, the need for repeated transfers of individual patients between psychiatric residents is reviewed in the light of educational necessities.

Adult↗
PubMed1987

Capgras syndrome--an unusual case and discussion of psychodynamic factors.

A case of Capgras syndrome associated with extreme violent behaviour is described. The patient's psychodynamics support the belief that the Capgras delusion initially arises from an altered affective response towards one or more others and proceeds to intolerable ambivalent feelings. This ambivalence is neutralised through the imagined existence of doubles.

Capgras Syndrome↗