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Biomedical subjects

C Cunningham

Publications and source records attributed to C Cunningham.

At least 19 recordsLinked to original sources

The UL13 virion protein of herpes simplex virus type 1 is phosphorylated by a novel virus-induced protein kinase.

Herpes simplex virus type 1 (HSV-1) induces a protein kinase (PK) activity in infected cell nuclei. In vitro, the enzyme is able to phosphorylate exogenous casein (albeit inefficiently) but not protamine, can use ATP or GTP as a phosphate donor, is stimulated by high salt concentrations and is insensitive to inhibition by heparin. On the basis of these properties, the PK appears to be distinct from previously described cellular enzymes and from the cytoplasmic PK encoded by the viral US3 gene. A major substrate of the enzyme in vitro is a virus-induced protein with an Mr of 57000 (Vmw57). The gene encoding Vmw57 was mapped using recombinants between HSV-1 and HSV-2 to a region of the virus genome containing genes UL9 to UL15. Use of a monospecific rabbit antiserum showed that Vmw57 is a virion structural protein encoded by gene UL13. These results, in conjunction with previous reports that the UL13 protein contains PK sequence motifs, support the notions that the nuclear PK and Vmw57 are identical, and that the observed reactivity is due to autophosphorylation.

Animals

Passive tube and suction drainage after elective cholecystectomy--a comparison using ultrasonography.

Daily ultrasonography of the gallbladder bed was performed in patients with suction or passive tube drains after elective cholecystectomy. A total of 19 patients was randomized to suction drainage and 17 to passive tube drainage. A policy of early drain removal was followed. No significant difference was found between the volume drained and the size of collection detected in either group. Significant bile leaks were detected and were adequately drained by suction and passive tube drains. There were no complications from drains. In view of these findings, we advocate short-term drainage of the gallbladder bed after both open and laparoscopic cholecystectomy using the drain of the surgeon's choice.

Abdomen

Sequence of a cellulase gene from the rumen anaerobe Ruminococcus flavefaciens 17.

A cellulase gene (endA) was isolated from a library of Ruminococcus flavefaciens strain 17 DNA fragments inserted in pUC13. The endA product showed activity against acid-swollen cellulose, carboxymethyl-cellulose, lichenan, cellopentaose and cellotetraose, but showed no activity against cellotriose or binding to avicel. Nucleotide sequencing indicated an encoded product of 455 amino acids which showed significant sequence similarity (ranging from 56% to 61%) with three endoglucanases from Ruminococcus albus, and with Clostridium thermocellum endoglucanase E. Little relatedness was found with a cellodextrinase previously isolated from R. flavefaciens FD1.

Amino Acid Sequence

A proposed role for IF-3 and EF-T in maintaining the specificity of prokaryotic initiation complex formation.

Initiation factor-free 30S subunits of E. coli ribosomes bind aminoacyl-tRNAs more efficiently than fMet-tRNA(fMet). Elongator-tRNA binding was unaffected by IF-1 or IF-2 but was inhibited by IF-3. Their combination reduced this binding up to 40% and stimulated that of fMet-tRNA(fMet). Unexpectedly, EF-T also prevented elongator-tRNA binding by complexing both to the 30S and to the aminoacyl-tRNAs. Using AUGU3 as mRNA, elongator-tRNAs competed with fMet-fRNA(fMet) and with tRNA(fMet), fMet-tRNA(fMet) reacted with puromycin after addition of 50S subunits suggesting that it occupied the P site. EF-T directed binding of phe-tRNA to the 30S.AUGU3 complex at the A site only if fMet-tRNA(fMet) or tRNA(fMet) filled the P/E site. We propose that one function of EF-T may be to prevent the entry of aminoacyl-tRNAs into the 30S particle during initiation. The possibility that a special site for fMet-tRNA resides on 16S rRNA is also discussed.

Binding Sites

Reduction of sensitization induced by blood transfusion in the rat by monoclonal antibodies.

Primary and secondary alloantibody responses were monitored in (AOxPVG)F1 hybrid rats after three transfusions of DA blood; the initial transfusion was either untreated or pretreated with monoclonal antibody directed to class I antigens or other cell surface markers. Mean antibody activity in recipient sera against class I DA antigens was significantly decreased by pretreatment with the monoclonal antibodies. The most marked suppression was associated with pretreatment by antibodies to the four major nonoverlapping epitopes of the RT1Aa antigen. Subsequent transfusions of DA blood failed to stimulate a secondary response. Crossreactivity of the alloantibody reactivity with BDIX antigens was diminished by pretreating the transfusions with rat anti-RT1A antibodies and, to a lesser extent, with a mouse monoclonal antibody (OX-18) to a common class I determinant. Monoclonal antibody pretreatment had no effect on the humoral response to class II DA antigens. These studies indicate that blood transfusions pretreated with monoclonal antibodies induce a less-potent cytotoxic humoral immune response and that reactivity is most effectively suppressed by completely masking the class I antigen. This technique may prove of clinical value in preventing the sensitization caused by blood transfusions in potential transplant recipients.

Animals

Comparative sequence analysis of the long repeat regions and adjoining parts of the long unique regions in the genomes of herpes simplex viruses types 1 and 2.

We report the determination of the DNA sequence of the long repeat (RL) region and adjacent parts of the long unique (UL) region in the genome of herpes simplex virus type 2 (HSV-2) strain HG52. The DNA sequences and genetic content of the extremities of HSV-2 UL were found to be closely similar to those determined previously for HSV-1. The 5658 bp sequenced at the left end of HSV-2 UL contained coding regions for genes UL1 to UL4 plus part of UL5. The 4355 bp sequenced at the right end of UL contained coding regions for part of gene UL53, and the whole of genes UL54 to UL56. Comparison of the HSV-1 and HSV-2 UL56 sequences led to a correction in the published HSV-1 UL56 reading frame. The HSV-2 RL region, including one copy of the a sequence, was determined to be 9263 bp, with a base composition of 75.4% G+C and with many repetitive sequence elements. In HSV-2 RL, sequences were identified corresponding to HSV-1 genes encoding the immediate early IE110 (ICP0) transcriptional regulator and the ICP34.5 neurovirulence factor; the former HSV-2 gene was proposed to contain two introns, and the latter one intron. Downstream of the HSV-2 immediate early gene, the RL sequence encoding the latency-associated transcripts (LATs) was found to be dissimilar to that in HSV-1; the probable LAT promoter regions, however, showed similarities to HSV-1. Properties of the LAT sequences in both HSV-1 and HSV-2 were consistent with LATs being generated as an intron excised from a longer transcript.

Amino Acid Sequence

Identification and characterization of a novel non-infectious herpes simplex virus-related particle.

During gradient purification of herpes simplex virus type 1 (HSV-1) two bands of particles were observed: a sharp lower band and a more diffuse upper band. The lower band contained almost exclusively HSV-1 virions (H particles) whereas the upper band consisted of membrane-enclosed particles (L particles). These L particles resembled the virions in appearance, but lacked the viral nucleocapsid and were not infectious. Many polypeptides of the viral envelope and the tegument were common to both types of particles. The H particles had polypeptide profiles typical of HSV virions. The L particles contained at least three phosphoproteins (175K, 92K and 55K) and a further two phosphorylated polypeptides not normally observed in virion profiles which comigrated with the 134K and 60K glycoproteins. This clearly indicates that the novel L particles were not merely virions which had formed without the inclusion of a nucleocapsid or virions which had subsequently lost their nucleocapsid during preparative handling. Thus these novel L particles are genuine products of the infectious processes occurring when HSV-1 replicates.

Animals

Factors relating to self-sufficiency in children with Down's syndrome.

An index of self-sufficiency in children with Down's syndrome was developed for use in a study of the process of adaptation in families living in the Greater Manchester area. The children were 6-14 years old, and living at home. Index scores were based on the mothers' responses to a questionnaire covering their children's personal and domestic functioning and community self-sufficiency, and were obtained from 111 of the 117 mothers who took part in the study. A wide range of child- and family-related variables were found to be significantly associated with self-sufficiency scores on a univariate level. Multiple regression analysis was used to identify those variables which best predicted the level of self-sufficiency achieved. After the child's mental age, the most significant variables were excitability, behaviour problems, the extent the mother used practical means of coping, and the level of social activity experienced by the child. Together, these five variables explained 63% of the variance in self-sufficiency scores. The dynamics by which such factors may relate to self-sufficiency in children with Down's syndrome are discussed, and intervention aimed at promoting the use of practical ways of coping by parents is suggested.

Activities of Daily Living

Factors related to stress and satisfaction with life in families of children with Down's syndrome.

In a study of families of children with Down's syndrome, measures of parent, family and child characteristics were obtained from mothers and fathers. Multivariable analyses investigated their relationships to outcome measures of psychosomatic symptoms of stress and parents' perceived satisfaction with life. Personality factors were related to outcome for both parents. For mothers, the children's levels of behaviour problems, excitability and self-sufficiency were strongly related to outcome. Coping strategies, family relationships and socio-economic factors also showed significant effects. For fathers, child characteristics were not related to outcome. The marital relationship was an important factor and there was evidence that factors external to the family acted as stressors.

Adaptation, Psychological

Is the appearance of children with Down syndrome associated with their development and social functioning?

The appearance of 111 children with Down syndrome, aged six to 14 years, was rated by their class teachers as part of a larger study on factors associated with their development, social life-style and family functioning. There were no significant associations between measures of child development, communicative or independent functioning, social life, behaviour problems or with parental stress, parent-child relationships or quality of family life. Typical features of Down syndrome are not major correlates of development and social functioning, and no support could be found to justify routine cosmetic surgery aimed at ameliorating such features.

Achievement

The detection of antibodies in pregnancy: a comparison of two assay systems.

In this study we have compared the ability of two assay systems, erythrocyte antibody rosette inhibition (EAI) and cellular enzyme-linked immunospecific assay (CELISA) to detect maternal alloantibody activity during pregnancy. Antibody activity to antigens on paternal lymphocytes was present in nine of 23 primigravid sera tested by EAI and in seven of 23 by CELISA. In multiparous sera, antibodies directed to paternal lymphocytes were detected in 11 of 15 individuals by EAI and in six of 15 by CELISA. The techniques correlated significantly when assaying the humoral response in sera from multiparous women. The lack of correlation when assaying primigravid sera suggests that both assays encounter difficulty in detecting the low titres of antibodies present.

Enzyme-Linked Immunosorbent Assay

Factors related to the academic attainments of children with Down's syndrome.

The attainments in reading, number and writing skills, of 117 children with Down's syndrome, aged 6 to 14 years, were assessed using checklists completed by teachers. In a study of child and family functioning a wide range of variables was measured and the relationships of these to academic attainments were investigated using multivariable analysis. The children's mental age scores were most strongly related to academic attainments scores, but, in addition, type of school attended, gender, chronological age and fathers' scores on a measure of locus of control were significantly related. The results are discussed in terms of their implications for educational placement and curriculum, and the role of fathers in their children's education.

Achievement

Choroidal lesions in patients with AIDS.

Seven cases of bilateral, scattered, yellow-white choroidal lesions have been seen in AIDS patients since January 1988. One resulted from presumed extension of cryptococcal meningitis into the optic nerve and choroid. All the remaining six patients had pneumocystis pneumonia at some time during the course of the disease and were receiving aerosolised pentamidine therapy. None died quickly of disseminated Pneumocystis carinii infection, unlike previously reported patients. Mycobacterial infection was also present in five of these six patients. The differential diagnosis of this entity in AIDS patients is discussed.

Acquired Immunodeficiency Syndrome

Tube feeding in the real world: formulas, equipment, finances, and feeding problems.

When selecting enteral feedings for infants and children on continuous peritoneal dialysis care should be taken to meet individual needs to provide for nutritional adequacy and normal growth rates. This requires a combination of complete feedings plus modules. The feedings should be evaluated frequently to adjust for growth and changes in renal function or treatment.

Child