PubMed Health⌕ Search

Biomedical subjects

J Kennard

Publications and source records attributed to J Kennard.

At least 19 recordsLinked to original sources

Efficient herpes simplex virus type 1 (HSV-1) capsid formation directed by the varicella-zoster virus scaffolding protein requires the carboxy-terminal sequences from the HSV-1 homologue.

The scaffolding protein and associated protease of the human herpesvirus varicella-zoster virus (VZV), encoded by genes 33.5 and 33 respectively, were synthesized in insect cells using a baculovirus expression system. The expressed 33.5 product formed numerous long, flexible, hollow rods, and in this respect different from the herpes simplex virus type 1 (HSV-1) homologue which forms large aggregates consisting mainly of fibrous material interspersed with scaffold-like particles. Removal of 27 amino acids from the carboxy terminus of the VZV scaffolding protein by the gene 33 protease or expression of the cleaved product did not result in any discernible change in the morphology of the scaffolding protein. Again, this was in marked contrast to the situation in HSV-1 where removal of the 25 carboxy-terminal amino acids from the scaffolding protein by the associated protease or expression of VP22a results in the formation of large numbers of scaffold-like particles. Despite these differences, when cells were multiply infected with baculoviruses expressing the HSV-1 capsid shell proteins and the VZV scaffolding protein complete capsids were observed, suggesting that the VZV protein could act as a scaffold for the assembly of the HSV-1 capsid shell. The efficiency of capsid assembly was increased substantially by exchanging the 23 carboxy-terminal amino acids of the VZV scaffolding protein for the corresponding 22 carboxy-terminal amino acids of the HSV-1 homologue, supporting previous work which showed that this region was critical for the formation of intact capsids.

Amino Acid Sequence↗

The 25 amino acid residues at the carboxy terminus of the herpes simplex virus type 1 UL26.5 protein are required for the formation of the capsid shell around the scaffold.

Herpes simplex virus type 1 (HSV-1) polypeptides specified by overlapping genes UL26 and UL26.5 form a scaffold around which the icosahedral capsid shell is assembled. In a series of cleavage events catalysed by the UL26-encoded protease, the full-length UL26 product is processed into capsid proteins VP24 and VP21 and the UL26.5 protein is converted into the capsid protein VP22a by the loss of 25 amino acids from its carboxy terminus. The roles of the UL26 and UL26.5 products were investigated using the baculovirus expression system, focusing on the function of the 25 residues cleaved from the UL26.5 protein. A key conclusion from electron microscopic analysis and protein expression studies is that the 25 amino acids at the carboxy terminus of the full-length UL26.5 protein are required for the interaction of the capsid shell proteins with the scaffold in the formation of intermediate capsids. When cells were multiply infected with baculoviruses expressing a truncated form of the UL26.5 product corresponding to VP22a and the essential components of the capsid shell, no capsids were detected, whereas large numbers of capsids were observed when the full-length UL26.5 product was used as a scaffold. The results are consistent with the proposal that cleavage of the UL26.5 product occurs after capsid assembly or when the UL26.5 protein is in a complex with one or more capsid shell proteins. Expression of VP22a in the absence or presence of capsid shell proteins resulted in the formation of large numbers of 60 nm scaffold-like particles. Since VP22a expressed from baculovirus was unable to participate in capsid assembly, these particles cannot be intermediates in the capsid assembly pathway but may be similar in structure to the protein cores present in HSV-1 immature (B) capsids.

Amino Acid Sequence↗

Localization of the herpes simplex virus type 1 major capsid protein VP5 to the cell nucleus requires the abundant scaffolding protein VP22a.

The intracellular distributions of three herpes simplex virus type 1 (HSV-1) capsid proteins, VP23, VP5 and VP22a, were examined using vaccinia virus and plasmid expression systems. During infection of cells with HSV-1 wild-type virus, all three proteins were predominantly located in the nucleus, which is the site of capsid assembly. However, when expressed in the absence of any other HSV-1 proteins, although VP22a was found exclusively in the nucleus as expected, VP5 and VP23 were distributed throughout the cell. Thus nuclear localization is not an intrinsic property of these proteins but must be mediated by one or more HSV-1-induced proteins. Co-expression experiments demonstrated that VP5 was efficiently transported to the nucleus in the presence of VP22a, but the distribution of VP23 was unaffected by the presence of either or both of the other two proteins.

Biological Transport↗

Gastrointestinal responses to oats consumption in young adult and elderly rats: digestion, large bowel fermentation and crypt cell proliferation rates.

The present experiment was designed to test the hypothesis that ageing modifies the gastrointestinal responses to a change in diet composition. Rats of the Wag/Rij strain, either young adult (4 months of age) or elderly (27 months of age), were given a basal semi-purified diet or a diet of similar major nutrient composition containing 500 g oatmeal/kg for 17-18 d. Elderly rats digested the dry matter (DM) and organic matter (OM) of both diets less well than did their young adult counterparts, with more of this digestion occurring in the distal intestine. The greater flow of OM to the caecum of oats-fed animals was accompanied by significant reductions in caecal pH and increases in caecal total short-chain fatty acids (SCFA) concentration which appeared to be independent of age. However, young adults responded to feeding on oats by showing a much larger increase in the molar proportion of butyrate (332%) than did elderly animals (79%). Elderly rats had longer duodenal villi than did young adults but effects of age or diet were not detectable at other sites. With both age-groups oats consumption was associated with significant stimulation of crypt cell proliferation rate (CCPR) in the small intestine and caecum, but for the colon there was a significant reduction in CCPR with oats feeding. A reduced ability of the aged large bowel (LB) to produce butyrate may contribute to the prevalence of LB disorders in the elderly.

Aging↗

Frog cones as well as Müller cells have peroxisomes.

We have localized D-amino acid oxidase in peroxisomes of frog retina using cerium procedures on tissue fixed in mixtures containing lower concentrations of glutaraldehyde than we had previously used in our cytochemical studies of this enzyme. We find the Müller cells of these preparations contain a more striking population of peroxisomes than had previously been thought: the D-amino acid oxidase-containing bodies are especially concentrated near the outer limiting membrane, but appreciable numbers are also found in the outer plexiform layer and near the inner limiting membrane. In addition, we find peroxisomes to be present in frog cone photoreceptors, particularly in zones near the ellipsoid. To our knowledge peroxisomes have not been described hitherto in vertebrate photoreceptors. Possible roles for the peroxisomes of the neural retina include participation in the metabolism of lipids (e.g. those of the cones' oil droplets, or of the outer segment) and involvement in oxidation of transmitter-related amino acids and of other small molecules.

Animals↗

Peroxisomal oxidation of thiazolidine carboxylates in firefly fat body, frog retina, and rat liver and kidney.

D-amino acid oxidase is a widely distributed peroxisomal enzyme whose principal natural substrates are still unknown. Thiazolidine carboxylates, their derivatives and relatives, and the intermediates in their metabolism are among the more plausible substrate candidates. Using a cytochemical procedure, we have explored the distribution of peroxide-generating enzymatic activity against two thiazolidine carboxylates. We find that these compounds are effective substrates for peroxisomal oxidation in a variety of tissues that contain peroxisomal D-amino acid oxidase. Reaction was seen in the "classical" peroxisomes of rat liver and kidney, the peroxisomes of the fat body of firefly and of Drosophila and the peroxisomes of frog retina. Interestingly, both with the thiazolidine compounds and with more traditional D-amino acid oxidase substrates, the fireflies' photocyte granules, which are peroxisomes, lack activity.

Animals↗

Peroxisomes in the head of Drosophila melanogaster.

Peroxisomes were localized in the head of wild-type and mutant strains of Drosophila melanogaster by use of a cytochemical method for the demonstration of D-amino acid oxidase activity. With similar techniques we had found previously that vertebrate photoreceptors have few, if any, bodies with cytochemically demonstrable oxidase activity, but that the pigment epithelial cells adjacent to the photoreceptors have a substantial population of such bodies. Peroxisomes in Drosophila were very abundant in the fat body. Probable peroxisomes were also present in the peripheral retina of the eye, including in retinular (retinula) and pigment cells, but there were very few of them. Thus, our results suggest that the fat body, which lies adjacent to the eye, is the principal site of peroxisomal function in the head. Peroxisome functions in the Drosophila head may include participation in the genesis of eye pigments.

Allopurinol↗

The total score of the Crown-Crisp Experiential Index: a useful and valid measure of psychoneurotic pathology.

The Crown-Crisp Experiential Index (CCEI) was designed as a measure of neurotic symptomatology. The tendency has been to report upon its six separate scales and to ignore the total score. We report on the use of the CCEI in a detailed interview study of 208 40-49-year-old women from a local community and 40 patients of the same age range and sex from a psychiatric hospital. In this study, scores on the six scales of the CCEI were shown to be highly intercorrelated. A case is made for combining the six scale scores to form an overall score of neurotic pathology. This score was validated against a number of variables. It was shown to be significantly related to psychiatric patient status, negative self-evaluation, level of severity of current symptoms, evidence of previous psychiatric episodes, previous psychiatric treatment and psychiatric symptoms in childhood. These validation variables were themselves intercorrelated but severity of current symptoms, self-evaluation and childhood symptoms had significant independent effects. It is concluded that scores on the six scales of the CCEI may be less important than the total score which provides a useful and valid measure of psychoneurotic pathology and has particular application as a screening instrument in community surveys.

Adult↗

What does the MMPI dependency scale really measure?

Examined the mean DY score of various clinical and nonclinical groups (N = 855). It was significantly higher for females, whether patients or nonpatients; nonpatients with a high total score and high scores on several subscales of the Crown Crisp Experiential Index of neurotic symptomatology; psychiatric patients in general; patients and nonpatients with a high modified Zung depression score; neurotic as opposed to endogenous depressives; suicide attemptors, especially non-serious ones; Ss with early bereavement or separation particularly if followed by poor replacement care; Ss with poor quality marriages and husband dominant marriages as measured by the Ryle Marital Patterns Test. The DY Scale relates directly with the PT and D Scales and inversely with the Do Scale. Separation of the test items into those that were and were not predominantly depressive revealed that most, though not all, significant associations were due to the depressive component, which it was suggested should be markedly diminished.

Adult↗

Marriage and mental illness.

Two female psychiatric patient samples were examined--240 women, aged 20 or over, from North East Scotland; and 44, aged 40 to 49, from Chichester, West Sussex. There was also a Chichester community sample of 230 women of similar age-range. The N.E. Scotland psychiatric patients with poor marriages broke down significantly earlier, and the delay between marriage and first breakdown was significantly shorter. This group also tended to have a neurotic rather than an endogenous type of depression. The poor marriages of the Chichester psychiatric patients were, in the main, similar to those of the Chichester non-patients, but the patients demonstrated significantly more disturbance of sexual relationships, and their in-laws were significantly more disapproving.

Adult↗

A new murine lymphocyte alloantigen, Ly-21.2, mapping to the seventh chromosome.

Using a monoclonal antibody raised by fusing spleen cells from A/J mice, immunized with B10.A splenocytes and lymph-node cells, with a BALB/c myeloma, we have described a new surface alloantigen, Ly-21.2, Ly-21.2 is present in varying amounts in all lymphoid tissues, is not detectable in the brain, kidney, lung or erythrocytes, and is found in only trace amounts in the liver. Strain distribution studies showed that Ly-21.2 is present in all strains examined, including B10, except the A strain and segregation analysis of (A/J x B10) F2 mice showed that Ly-21.2 expression (1) is encoded by one gene and (2) is linked to albinism on chromosome 7. Studies performed on mice developing T-cell leukemia showed that, regardless of the etiologic agent, Ly-21.2 expression increases dramatically in mice with overt leukemia. In addition, preliminary studies suggest that expression of Ly-21.2 is linked to increased susceptibility of mice to Friend-virus-induced erythroleukemia.

Albinism↗

The mental health of early mother separated women.

A community based research project was undertaken to discover whether early mother separation was related to adult mental disorder. A population sample of 73 women aged 40-49, who experienced continuous mother absences in excess of 1 year due either to family difficulties (n = 42) or external factors (n = 31), were interviewed about early life experiences and mental health. Controls (n = 69) matched for parental social class and age at father death were similarly interviewed. Three self-administered tests, the Middlesex Hospital Questionnaire, a modified Zung Depression Scale and the Navran Dependency Scale of the MMPI were also completed. It was shown that separation alone was unrelated to adult psychopathology or mental disorder. Poor preseparation maternal relationships, both alone and in combination with two or more changes of care plus unsatisfactory replacement care, contributed to an increase in psychiatric morbidity and psychopathology.

Adolescent↗

Precise mapping of the gene for Ly-21.2 on the 7th chromosome.

We have recently described a murine lymphocyte alloantigen, Ly-21.2, and showed that the gene which controls Ly-21.2 expression is linked to albinism on the 7th chromosome. In order to map the gene more precisely, we have studied the linkage of Ly-21.2 with two other genetic markers on the 7th chromosome, the electrophoretic variant of the beta chain of haemoglobin and glucose phosphate isomerase, in (A/J x C57BL/10)F2 mice. The results of these 3-point cross studies show that the gene encoding Ly-21.2 maps 27 units distal to albinism.

Albinism↗

Some marital and child-rearing characteristics of early mother-bereaved women.

A sample of 160 female, psychiatric patients from North-east Scotland whose mothers died before they were aged 11 was compared with 80 non-bereaved, female, psychiatric patients, matched by decade of birth, from the same area. Six subgroups of the bereaved patients classified according to the events which followed the bereavement were also examined. In addition, samples of 44 and 27 women from the Chichester general population, whose mothers died before age 11 and from 11 to 19 respectively, were paired by age, parental social class and age at death of father, with Chichester women who were not mother-bereaved. Comparisons were made in respect of age at marriage, relative age of subject and marital partner quality and fate of marriage, delay between marriage and birth of first child, total number of children, and ability to cope with the birth and subsequent child-rearing. The early bereaved women showed a tendency to marry younger men but otherwise their marriages were no different from those of the controls. The early bereaved had more difficulties with child-rearing, particularly when their children reached adolescence. Surprisingly, the findings for the six subgroups were not appreciably different from those of the total bereaved patients.

Adolescent↗