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Biomedical subjects

C Cunningham

Publications and source records attributed to C Cunningham.

At least 55 records · Page 3Linked to original sources
PubMed1986

The effect of cyclosporine on humoral and cellular alloreactivity to allogeneic pregnancy in rats.

We have evaluated the effect of a therapeutic dose (10 mg/kg/day) of the immunosuppressant cyclosporine (CsA) on humoral and cell-mediated immunity in rats during an allogeneic first pregnancy. Virgin female Lewis rats mated with DA males and treated with CsA vehicle produced a humoral response, as measured by both the erythrocyte rosette inhibition (EAI) and indirect hemagglutination assays. The capacity of Lewis splenocytes to mediate a graft-versus-host (GVH) reaction in six-week old F1 (Lewis X DA) hybrid rats was unaffected by either pregnancy or CsA. In mothers treated with CsA, however, no antibody production was detected, and a significant reduction in GVH reactivity was observed using their cells. This reduction was specific for the paternal strain. When compared with vehicle-treated primiparas, suppression of the immune response by CsA had no effect on either the number or viability of fetuses present in utero at day 20. These data suggest that antipaternal antibodies may not be essential to protect the fetus when there is concomitant suppression of the capacity of the mother's T cells to express a cell-mediated antipaternal response.

Animals↗
PubMed1986

Micro-scale ultracentrifugation as an alternative to ultrafiltration for the determination of the unbound fraction of phenytoin in human serum.

Free phenytoin has been determined using micro-scale ultracentrifugation followed by analysis by EMIT. The effect of temperature on the determined free fraction was investigated and the ultracentrifugation procedure validated against ultrafiltration. Ultracentrifugation gave free fractions which were on average 16% lower than those obtained using ultrafiltration, but correlation was good, as was the correlation with measurements of total phenytoin (r = 0.90). Micro-scale ultracentrifugation is a simple procedure which can be of great utility in the measurement and investigation of free drug levels.

Blood Proteins↗
PubMed1985

Amelioration of cyclosporin-induced nephrotoxicity in rats by induction of hepatic drug metabolism.

The aim of this study was to determine the effect of altered hepatic drug metabolism on the nephrotoxic and immunosuppressive properties of cyclosporin A (CsA) in the rat. From a consideration of the structures of those CsA metabolites identified so far, it seemed probable that the metabolism of CsA would occur at the hepatic cytochrome P-450 (cyt P-450) enzyme system. CsA (50 mg/kg/24 hr) administered orally for 14 days resulted in significant increases in both serum urea concentration and urinary N-acetyl-beta-D-glucosaminidase activity, accompanied by renal proximal tubular vacuolation. The concomitant administration of either Aroclor 1254 (25 mg/kg/24 hr, i.p.) or phenobarbitone (PB) (40 mg/kg/24 hr, i.p.) but not 3-methylcholanthrene (3-MC) (15 mg/kg/72 hr, i.p.) resulted in abolition of the nephrotoxicity, assessed both biochemically and histologically, whilst the suppressive effect on the humoral response to SRBC was unaltered. Phenobarbitone also significantly decreased serum CsA concentrations. These results suggest that the PB-inducible set of cyt P-450 isoenzymes may be responsible or partly responsible for hepatic CsA metabolism.

Animals↗
PubMed1985

Isolation and point of action of a factor from Escherichia coli required to reconstruct translation.

To study the mechanism of translation we have attempted to reconstruct the process from purified components. Protein synthesis was programmed by the RNAs of wild-type or amber mutants of bacteriophages f2 or MS2. Translation programmed by MS2 or f2am3 RNA does not occur using ribosomes, precharged aminoacyl-tRNAs, and the sum of the purified proteins involved in initiation (initiation factors; IF-1, IF-2, and IF-3), propagation (elongation factors; EF-Tu, EF-Ts, and EF-G) and termination (release factors; RF-1 or RF-2) of protein synthesis. The requirement for a protein called W was demonstrated. Protein W was purified free of all translation factors, activating enzymes, and other proteins such as the RR, "rescue," and EF-P implicated in translation. The stimulation of propagation by W depended on the position of the amino acid residue to be added in the synthesis of the NH2-terminal hexapeptide of the coat protein. In the reconstructed system, with the sum of all translation factors but in the absence of W, only dipeptides and smaller quantities of tripeptides were synthesized under the direction of f2am3 RNA. W stimulated the synthesis of the hexapeptide, fMet-Ala-Ser-AspNH2-Phe-Thr directed by this RNA. In addition, W stimulated ejection of non-cognate tRNAs that bind to ribosomal particles.

Bacterial Proteins↗
PubMed1985

The role of polypeptides L and NS in the transcription process of vesicular stomatitis virus New Jersey using the temperature-sensitive mutant tsE1.

The roles of the L and NS polypeptides in transcription by vesicular stomatitis virus New Jersey were studied using a mutant, tsE1, which contains a temperature-sensitive transcriptase and an altered NS polypeptide, both phenotypic changes being the consequence of the ts mutation. Mutant tsE1, its revertant (tsE1/R1) and the wild-type virus were dissociated into sub-viral fractions and, after reconstitution of these fractions in all combinations, the transcriptase was assayed in vitro at the permissive (31 degrees C) and restrictive (39 degrees C) temperatures. Reconstitution of the pellet fractions (containing polypeptide N complexed with the virion RNA) and the supernatant fractions (containing polypeptides L and NS) restored transcriptase activity at 31 degrees C in all combinations, but at 39 degrees C transcription was observed only in the presence of the supernatant fractions of wild-type and revertant viruses but not in the presence of the supernatant fractions of tsE1. When the pellet fractions and the L fractions were reconstituted, the transcriptase activity was restored in all combinations both at 31 degrees C and 39 degrees C. However, in vitro transcription at 39 degrees C by reconstituted pellet and L fractions was strongly inhibited when the NS fraction of tsE1 was also added, while addition of the NS fractions of wild-type and revertant viruses had no effect. Since only traces of polypeptide NS were present in the L fractions and none in the pellet fractions, the results strongly suggest that polypeptide L is the transcriptase itself while polypeptide NS exerts some control over transcription.

DNA-Directed RNA Polymerases↗
PubMed1985

Temperature sensitivity of the transcriptase of mutants tsB1 and tsF1 of vesicular stomatitis virus New Jersey is a consequence of mutation affecting polypeptide L.

Two conditional transcriptase-negative mutants of vesicular stomatitis virus (VSV) serotype New Jersey, tsB1 and tsF1, their revertants tsB1/R1 and tsF1/R1 and the wildtype virus were dissociated into pellet, NS and L fractions and, after reconstitution of these in various combinations, the transcriptase activities were assayed in vitro at the permissive (31 degrees C) and restrictive (39 degrees C) temperatures. The pellet fractions contained the virion RNA-polypeptide N complexes, while the NS and L fractions were essentially pure preparations of these polypeptides. The synthesis of RNA by the reconstituted pellet and L fractions was inhibited at 39 degrees C only when the L fractions of tsB1 or tsF1 were used. Addition of the NS fractions to the reconstituted pellet and L fractions did not alter the rates of RNA synthesis. These results demonstrate that polypeptide L is the temperature-sensitive polypeptide of both mutants tsB1 and tsF1 and support previous observations that polypeptide L is the transcriptase itself. The fact that a second mutant of complementation group F, tsF2, is transcriptase-positive but replicase-negative suggests that polypeptide L is involved both in transcription and replication. Intracistronic complementations may account for the observation that the temperature-sensitive mutations affect polypeptide L in complementation groups B and F.

DNA-Directed RNA Polymerases↗
PubMed1985

Training and education approaches for parents of children with special needs.

This is a review of attempts made to involve and to train parents in the endeavour of helping their children with special needs. The reasons for parent involvement are discussed, before describing and contrasting the variety of theoretical orientations and parenting skills that have been considered in this work, and the influences of parent and child characteristics. Detailed consideration is given to the methods used in training and their effectiveness. Although parent involvement can be said to be of value, more effort is required in terms of careful conceptualization and more elaborate multivariate research before definite answers may be provided for many of the issues raised.

Age Factors↗
PubMed1985

Inhibition of contact sensitivity reactions to DNFB by topical cyclosporin application in the guinea-pig.

Contact sensitivity skin reactions to dinitrofluorobenzene (DNFB) were inhibited by twice daily topical application of cyclosporin (CsA, 2%) in normal guinea-pigs and in those with enhanced contact sensitivity reactions following pre-treatment with cyclophosphamide. In contrast to oral administration of CsA (25 mg/kg) for 4 days, topical application of the drug over the same period did not result in systemic absorption (as measured by radioimmunoassay) or in any evidence of nephrotoxicity.

Administration, Topical↗
PubMed1977

Problems in diagnosis and management of children with cerebral palsy and deafness.

Problems in the diagnosis, management and educational placement of 10 children with cerebral palsy and deafness are reported. Serious inadequacies revealed by the study include delays in diagnosis, poor co-ordination of decision-making between services and frequent changes of school--all leading to unsatisfactory progress by these children.

Adolescent↗
PubMed1976

Alteration of mitochondrial function and lipid composition in Morris 7777 hepatoma.

Mitonchondria isolated from the Morris hepatoma 7777 demonstrated a markedly different phospholipid composition from those of control mitochondria, both with respect to the amounts of the various types present and the fatty acid composition. The level of polyunsaturated fatty acids in the mitochondrial phospholipids was lowered, wheras there was an increase in the level of monounsaturated fatty acids. Moreover, the usual distribution of saturated fatty acids at position 1 and polyunsaturated fatty acids at position 2 does not exist in hepatoma phospholipids; a high percentage of monounsaturated fatty acids was found at both positions. The cardiolipin content was lower in hepatoma mitochondria (3.7%) than in livers of animals with hepatomas (5.2%). There was, however, some compensation in the amount of acidic phospholipids in these mitochondria due to an increase in phosphatidylserine (4.9% versus 1.3%). The force-area curves of the hepatoma phospholipids spread on a monomolecular film demonstrated a smaller area per molecule than those from liver mitochondria. The zeta potential of liposomes of the hepatoma phospholipids (-45) was less than those of control mitochondria (-81), as determined by microelectrophoresis. The calcium-stimulated phospholipase A activity of the hepatoma mitochondria appeared to be more readily expressed than the same activity in liver organelles. The maximal activity was lower, however, than that noted in liver mitochondria. Furthermore, by following the incorporation of [3H]ethanolamine into mitochondria phospholipids, it was established that the conversion of glycerophosphorylethanolamine to glycerophosphorylcholine was increased in the hepatoma. These observations suggest dramatic changes in phospholipid metabolism in the hepatoma, at the level of both the endoplasmic reticulum and the mitochondrion. Accompanying the changes in phospholipid compositon and metabolism were alterations in mitochondrial energy-linked processes. The hepatoma mitochondria demonstrated lower respiratory control ratios even when isolated in an isotonic solution containing 1mM ethylenediaminetetraacetate and bovine serum albumin (0.5 mg/ml). This was due to increased state 4 respiration.

Animals↗