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Biomedical subjects

P Maher

Publications and source records attributed to P Maher.

68 records · Page 4Linked to original sources

Cytomegalovirus infection in cardiac transplant recipients associated with chronic T cell subset ratio inversion with expansion of a Leu-7+ TS-C+ subset.

Lymphocyte subsets were analysed in 18 patients during the first 3 years after cardiac transplantation. The patients received Cyclosporin A and prednisolone for maintenance immunosuppression. Serological evidence of active cytomegalovirus (CMV) infection was found in 13 cases (72%), and in 12 of these an inversion usually of the T helper/T suppressor-cytotoxic ratio (TH/TS-C) was detected. T subset inversion usually preceded the diagnostic rise in CMV antibody titre. In 69% of patients with CMV the TH/TS-C ratio remained inverted throughout follow-up (245-951 days). Persistent T subset inversion was not found in all five patients who lacked serological evidence of active CMV. Chronic inversion consisted of an average increase in TS-C of 152% and an average decline in TH cells of 31% as compared to CMV negative patients. The proportion of lymphoid cells reacting with a phenotypic marker for natural killer (NK) cells (Leu-7) was increased by 83%. These alterations were also reflected in the absolute numbers of cells with these markers. Two-colour immunofluorescence analysis revealed that the expanded TS-C population present during chronic inversion was predominantly Leu-7+. As TS-C+ Leu-7+ cells in healthy persons may be hyporesponsive NK cells, a sustained increase in this cell type in allograft recipients could further reduce immunocompetence, thereby predisposing to superinfection or malignancy.

Adult↗

Does indomethacin cause extension of intracranial hemorrhages: a preliminary study.

Thirty-six infants who had an intracranial hemorrhage (diagnosed by cranial ultrasound) within four days after delivery (mean age 2.4 +/- 0.9 (SD) days), were reexamined at three- to seven-day intervals for extension of their intracranial hemorrhage. Seventeen infants had a patent ductus arteriosus and were treated with indomethacin after the initial intracranial hemorrhage was diagnosed. The age for starting indomethacin was 3.8 +/- 1.1 days. Nineteen infants did not have a patent ductus arteriosus and did not receive indomethacin. Both the indomethacin-treated and nontreated groups were similar in birth weight, gestational age, Apgar scores, gender, incidence of respiratory distress, as well as the location and the degree of hemorrhage in the initial scans. Only one of 17 (6%) infants who received indomethacin v tow of 19 (11%) infants who did not receive it, had extension of their initial intracranial hemorrhage. Although indomethacin may alter platelet function, it does not appear to cause extension of a preexisting intracranial hemorrhage.

Cerebral Hemorrhage↗

Structural changes in membranes produced by the binding of small amphipathic molecules.

In their interactions with membranes, amphipathic small molecules exhibit detergent-like properties. At sufficiently high concentrations (above their critical micelle concentrations, if they form micelles), they substantially dissolve membranes. At lower concentrations, between maximally antihemolytic and lytic, we show here that the amphipaths significantly perturb membrane structure. Each of six small-molecule amphipaths was shown by hygroscopic desorption filtration to induce the extraction of small but significant amounts of membrane components, partly in the form of vesicular fragments, from red blood cell membranes. These extracts were enriched in the lipid to protein ratio as compared to the intact membrane, and the protein composition was highly unrepresentative. A similar set of extractions from sarcoplasmic reticulum membranes was induced by the six amphipaths. We conclude that small-molecule amphipaths, at concentrations lower than lytic, promote gross redistributions of components in the plane of a membrane that result in the observed extractions.

Animals↗

A 200-kd protein isolated from the fascia adherens membrane domains of chicken cardiac muscle cells is detected immunologically in fibroblast focal adhesions.

On the premise that the fascia adherens of cardiac muscle cell intercalated disk membranes is a structure that is closely homologous to the focal adhesions formed by fibroblasts, a fascia adherens preparation was isolated from chicken cardiac muscle, and was analyzed for its protein composition. A prominent 200-kilodalton (kd) protein was purified from the fascia preparation and shown to be antigenically unrelated to several previously characterized cytoskeletal proteins, including cardiac myosin and vinculin. With monospecific antibodies to the 200-kd protein, an identical or closely similar intracellular protein was shown to be associated with the focal adhesion plaques of fibroblasts.

Animals↗

Analysis of lectin-specific cell surface glycoprotein on neuroblastoma cells.

The binding sites for the lectins wheat germ agglutinin, Ricinus communis agglutinin and concanavalin A on mouse neuroblastoma cell membranes were identified using SDS-gel electrophoresis in combination with fluorescent lectins. Ricinus communis agglutinin and wheat germ agglutinin were found to bind almost exclusively to a single polypeptide with an apparent molecular weight of 30 000. Concanavalin A labeled over 20 different polypeptides, most with molecular weights greater than 50 000. However, when the neuroblastoma cells were treated with concanavalin A so as to internalize all the concanavalin A binding sites visible at the level of the fluorescent microscope and the purified plasma membranes analyzed for their concanavalin A binding polypeptides, only four of the 20 glycopolypeptides were missing or significantly reduced in amount. Thus, these four high molecular weight concanavalin A-binding polypeptides appear to be the major cell surface receptors for concanavalin A. Binding studies with iodinated concanavalin A indicated that these polypeptides represented the high affinity concanavalin A binding sites (Kd = 2 . 10(-7) M). Low affinity concanavalin A binding sites were present on the cell surface after internalization of high affinity concanavalin A binding sites.

Animals↗

Differences in the redistribution of concanavalin A and wheat germ agglutinin binding sites on mouse neuroblastoma cells.

Concanavalin A (Con A), wheat germ agglutinin (WGA), and Ricinus communis agglutinin (RCA) bound with either 125I, fluorescent dyes, or fluorescent polymeric microspheres were used to quantitate and visualize the distribution of lectin binding sites on mouse neuroblastoma cells. As viewed by fluorescent light and scanning electron microscopy, over 10(7) binding sites for Con A, WGA, and RCA appeared to be distributed randomly over the surface of differentiated and undifferentiated cells. An energy-dependent redistribution of labeled sites into a central spot occurred when the cells were labeled with a saturating dose of fluorescent lectin and maintained at 37 degrees C for 60 min. Reversible labeling using appropriate saccharide inhibitors indicated that the labeled sites had undergone endocytosis by the cell. A difference in the mode of redistribution of WGA or RCA and Con A binding sites was observed in double labeling experiments. When less than 10% of the WGA or RCA lectin binding sites were labeled, only these labeled sites appeared to be removed from the cell surface. In contrast, when less than 10% of the Con A sites were labeled, both labeled and unlabeled Con A binding sites were removed from the cell surface. Cytochalasin B uncoupled the coordinate redistribution of labeled and unlabeled Con A sites, suggesting the involvement of microfilaments. Finally, double labeling experiments employing fluorescein-tagged Con A and rhodamine-tagged WGA indicate that most Con A and WGA binding sites reside on different membrane components and redistribute independenty of each other.

Animals↗

Alterations in chromatin of cells infected with RNA tumor viruses.

Chromatins were isolated from murine leukemia or sarcoma virus infected lymphocyte-like TB cells and compared by immunological and biochemical methods. Chromatin from virus infected cells did not fix complement as well as uninfected cell chromatin suggesting that conformational changes had occurred in chromatin from virus infected cells. This alteration was detected within 24 hours after infection. Infected cell chromatins, examined by electrophoretic methods after radiolabeling displayed alterations in nonhistone proteins, whereas the histones appeared unaltered. The non-histones were synthesized in greater amounts in infected compared to normal cells, particularly a 60,000 D protein, while the amount of histone did not vary. The above changes should not have been due to cell growth or cycle variations, for the cells had similar growth rates and were harvested from the same stage of cell confluency during exponential growth to ensure uniformity of culture conditions.

Cell Line↗

A change in the internal affinity of LK goat red-cell sodium pumps induced by high pH.

The K inhibition of ouabain-sensitive ATPase activity of LK goat red cell membranes is greatly reduced at high pH. This effect is reversible, and specific, since the apparent affinities for ATP, ouabain or external K do not alter. Anti-L-treated membranes show a similar alkali-induced affinity change, but have a lower pH optimum.

Adenosine Triphosphatases↗

Methemoglobinemia: an unusual complication of topical anesthesia.

Allergic reactions tend to be easily recognized and treated, but methemoglobinemia is a rare, life-threatening complication of topical anesthesia of which our staff was unaware until recently. Team work prevented a patient fatality. Directives to alert the staff to suspect methemoglobinemia in patients who develop cyanosis and decreased oxygen saturation levels after administration of topical anesthesia despite administration of oxygen will prevent fatalities in the future.

4-Aminobenzoic Acid↗

'Rejection or infection' predictive value of T-cell subject ratio, before and after heart transplantation.

Peripheral T-cell subsets were monitored in ten heart and two heart-lung recipients pre- and up to one year post-operatively. Prior to transplantation four patients had T-helper/T-cytotoxic suppressor ratios (TH/TS-C) above the range for normal healthy controls and all required treatment for rejection episodes, as compared with three of eight patients whose pre-transplantation ratios were within the normal range. No patient with high TH/TS-C ratios developed cytomegalovirus infection as compared with all of the eight patients with normal ratios. Post-transplantation cytomegalovirus infection was the major cause of alterations in TH/TS-C ratios. T-cell subset inversion always preceded the diagnostic rise in cytomegalovirus antibody titre in both primary and secondary cytomegalovirus infections. Inversion was also noted with Pneumocystis carinii infection. Reversal of the TH/TS-C ratio was due to a major increase in the absolute numbers of TS-C cells and was usually followed by a rise in the number of cells expressing a natural killer cell phenotypic marker (Leu-7). All patients with primary cytomegalovirus and two of four cases with secondary cytomegalovirus retained inversion throughout follow-up and showed significantly increased numbers of TS-C and Leu-7 bearing cells. However, the absolute numbers of TH fell by 200 days after transplantation in all patients irrespective of their TH/TS-C ratio. Although TH/TS-C ratio inversion was a predictor of cytomegalovirus infection, no association was found between changes in T-cell subsets after transplantation and rejection episodes.

Adult↗