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Biomedical subjects

C Cunningham

Publications and source records attributed to C Cunningham.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1984

Serum cyclosporin levels, hepatic drug metabolism and renal tubulotoxicity.

The present study was designed to examine inter-relationships between serum cyclosporin (CsA) levels, hepatic drug metabolising enzyme activity and CsA induced nephrotoxicity. CsA (25 mg/kg p.o.) was administered daily to male Sprague-Dawley rats: groups of animals were killed on days 0, 4, 7, 10 and 14 and thereafter at weekly intervals over the 7-week course of the experiment. Nephrotoxicity was evaluated by measuring tubular enzymuria and by light microscopy and serum CsA levels (parent drug plus certain metabolites) were determined by radioimmunoassay. The hepatic microsomal mono-oxygenase enzyme system was monitored by measurement of cytochrome P-450, aminopyrine N-demethylase and NADPH-cytochrome c reductase. Nephrotoxicity appeared within 4 days of starting treatment and continued for 4 weeks. Between weeks 4 and 6 there was a period of complete remission followed by the return of renal damage. Aminopyrine N-demethylase activity fell during the first 4 weeks. During the period of remission, however, N-demethylase activity rose to a point significantly higher than pretreatment values and serum CsA levels fell to their lowest concentration. With relapse, hepatic N-demethylase activity again fell below normal and serum drug levels rose to their pre-remission values. From the third week onward, changes in NADPH-cytochrome c reductase activity paralleled those in N-demethylase activity. The hepatic microsomal concentration of cytochrome P-450 did not, however, change significantly during the 7-week period of CsA treatment. Our results suggest that the spontaneous remission of CsA-induced nephrotoxicity is due to a reduction in circulating drug levels caused by increased hepatic CsA metabolism.

Animals↗
PubMed1984

Enhancement of high dose cyclosporin A toxicity by frusemide.

Adult Sprague-Dawley rats were given cyclosporin A (CyA), frusemide (Fr) or both drugs daily for 14 days. The doses of CyA (50 mg/kg) and Fr (5 mg/kg) were approximately 3-6 times and twice respectively those used in man. Fr on its own produced a diuresis lasting approximately 3 hr. This was characterized by a 10-fold increase in urine flow rate, a 40-fold increase in the rate of sodium excretion, and by 2- and 4-fold increases in urea and creatinine clearance rates, respectively. In addition, there was a doubling in urinary N-acetyl-beta-D-glucosaminidase (NAG) activity. After 4 days of combination treatment with CyA and Fr, the diuretic-induced increases in urine flow rate, sodium excretion and urinary NAG activity were similar to those following frusemide alone. However, urea and creatinine clearances did not increase during the diuresis. Fr itself did not impair renal function, but rats receiving only CyA did show elevations in serum urea and creatinine, with reductions in clearance rates, which progressed with time. There was also an increase in NAG enzymuria. When the two drugs were exhibited together, renal function was more severely impaired. All animals given CyA showed proximal renal tubular cell vacuolation: in half the damage was confined to the straight segment, while the rest showed additional severe convoluted segment change. Renal function was most abnormal in those rats in which both segments were affected. All animals given both drugs showed both straight and convoluted tubular abnormalities and a 2-fold increase in serum CyA levels. CyA-induced disturbances in hepatic function and lymphoid tissue atrophy were unaffected by the addition of Fr, nor did Fr affect the immunosuppressive action of CyA.

Acetylglucosaminidase↗
PubMed1984

Detection of a 16S rRNA . initiator-tRNA complex by a new selective labelling method.

Cupric-ion induced hydrolysis of [35S]Met-tRNA but not of N-formyl-Met-tRNAMetf permitted the specific terminal labelling of initiator tRNA. Initiator tRNA, labeled in this way, was suitable for sequence analysis without the need for further purification. By probing labeled initiator tRNA with specific RNases, changes in this molecule during its interaction with the 30S particle or with 16S rRNA were investigated. Initiation complexes were resistant to the action of single-strand, base-specific nucleases Bc and Phy M and, except for one base of the anticodon stem, were also resistant to digestion by the double-strand-specific V1 nuclease of Naja venom. In contrast, T1 RNase digestion of the initiator tRNA in the presence of 16S rRNA enhanced cleavage of bases in the T stem of the molecule.

Base Sequence↗
PubMed1983

Renal cadmium content in the West of Scotland.

The trace element content of kidneys has been documented in very few international centres. Significant differences can be demonstrated between the cortical and medullary levels of calcium, zinc and cadmium. For the West of Scotland the values for the latter are similar to those found in Scandinavia. There are significantly higher cadmium contents in subjects who smoke and who have evidence of ischaemic heart disease.

Adolescent↗
PubMed1983

Chemical restraint of wild horses: effects on reproduction and social structure.

Twenty-three (9 male, 14 female) wild horses (Equus caballus) in the Great Basin Desert were immobilized by ground techniques with succinylcholine chloride during 1,950 person-hr. Induction (means = 2.09 +/- 0.59 min) and recovery (means = 12.4 +/- 5.0 min) were rapid and most animals were returned in less than 10 min to original bands. Dosages ranged from 0.66-0.77 mg/kg body weight and neither abortions nor band changes in group membership resulted. However, a few concerted efforts up to 24 hr were needed to return some animals to original bands and three non-drug related mortalities occurred. The responses of bands to darted members and the overall influence of the operation on reproduction, movements, and social structure are presented.

Animals↗
PubMed1982

The importance of cadmium as a factor in calcified upper urinary tract stone disease--a prospective 7-year study.

The non-essential trace metal cadmium may cause major pathological effects on the kidneys. A group of coppersmiths who have been chronically exposed to cadmium poisoning was systematically studied over a 6-year period. The stone prevalence in the group is now just under 40% as compared with 3.5% in a general population. The blood cadmium levels have remained persistently elevated despite removal of the cadmium source. The measurement of cadmium as a means of monitoring chronic poisoning has been undertaken in terms of the prospective study in the coppersmiths and also in its relationship to other trace metals, namely serum zinc and copper. Urologists should be aware of the possibility of cadmium poisoning.

Cadmium↗
PubMed1982

Studies of lead and cadmium exposure in Glasgow, U.K.

Domestic water and whole blood samples were collected early in 1981 from two hundred volunteers living in the Glasgow area of Scotland, U.K. The concentration of lead in the water and blood samples, and of cadmium in the blood, was measured. The blood lead and cadmium concentrations were compared to those obtained in the Survey of 1979. There has been a fall in blood lead concentrations since the 1979 Survey. In contrast, the blood cadmium levels had remained similar. This diminution in blood lead concentration is attributed to a fall in water lead concentration caused by raising the pH of the water supply in the Glasgow area. The main determinant for cadmium in blood appears to be cigarette smoking habits, which had not changed.

Adolescent↗