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J Rogers

Publications and source records attributed to J Rogers.

At least 379 records · Page 21Linked to original sources

Perturbation of the autoimmune network. I. Immunization with anti-idiotypic antibodies prior to challenge with antigen induces quantitative variations in the autoantibody response.

The effect of immunization with anti-idiotypes on the production of autoantibodies subsequently induced with nominal antigen, thyroglobulin, was investigated in BALB/c mice with three distinct rabbit antibodies and one syngeneic monoclonal antibody (mAb) specific for an idiotype (Id62) borne on a mouse monoclonal autoantibody to thyroglobulin. In these in vivo experiments, dose, route and form of the anti-idiotypic immunization were kept constant, but the time interval between exposure to anti-idiotype and antigen challenge was varied. When the interval was short (two weeks), heterologous anti-Id62 antibodies predisposed to suppression of the autoantibody response in 2/3 instances. Suppression was also obtained in mice immunized with a syngeneic mAb directed against Id62. In each case, a prominent idiotype-positive (Id') response was measured in the serum. Adsorption/elution studies indicated that Id' molecules in suppressed mice were principally non antigen-binding. On the other hand, when the time interval between injections was long (14 weeks), mice preimmunized with one rabbit anti-Id62 antibody showed a markedly increased autoantibody response. The Id' component in enhanced mice was largely enriched for antibodies reacting with the antigen. These findings suggest that the state of activation of autoreactive clones and the type of anti-idiotypes used may be determinant factors in the overall effect of manipulation of autoimmune responses with anti-idiotypic antibodies.

Animals↗

Escherichia coli glutaminyl-tRNA synthetase: a single amino acid replacement relaxes rRNA specificity.

We described previously the isolation, by genetic selection, of a mutant of Escherichia coli glutaminyl-tRNA synthetase that misaminoacylates supFtRNATyr with glutamine. The single amino acid change responsible for the mischarging phenotype was identified at amino acid 235 in the translated glnS gene. The mutant, called glnS7, has an Asp----Asn change, and studies with the purified glnS7 gene product show it may mischarge a number of presumably different tRNAs. We have carried out extensive homology searches that show E. coli glutaminyl-tRNA synthetase shares regions of homology with other aminoacyl-tRNA synthetases, although little apparent similarity at the site of the glnS7 mutation. In addition to the conserved 'HIGH' motif implicated in aminoacyl adenylate formation, there are regions of homology of glutaminyl-tRNA synthetase with other synthetases which may be involved in tRNA binding. These include short stretches of homology in sequences acting as a tRNA 'anchor' as well as homology of some aminoacyl-tRNA synthetases to a recently identified motif in ribonucleoproteins. Therefore, our results show that E. coli glutaminyl-tRNA synthetase may share with other aminoacyl-tRNA synthetases regions responsible for tRNA binding, while other regions of the protein, of which the glnS7 mutation may be a component, are responsible for tRNA discrimination.

Acylation↗

Reading and interpreting genograms: a systematic approach.

Family physicians continue to struggle with the problem of how to make optimal use of family information in everyday clinical practice. One important task in addressing this problem is describing systematically the categories of family information that are incorporated into the usual clinical problem-solving process used by physicians. In this article the usefulness of the genogram as a data-gathering and assessment tool is reexamined, and six information categories that can be used for generating and testing clinical hypotheses are outlined. Three clinical case studies are presented to demonstrate how physicians can read and interpret genograms systematically.

Adjustment Disorders↗

Independent expression of a regulatory idiotype on heavy and light chains. A further immunochemical analysis with anti-heavy and anti-light chain antibodies.

The heavy (H) and light (L) chains of murine monoclonal autoantibody 62 reacting with thyroglobulin independently express idiotypic (Id) determinants that are very similar if not identical with the Id62 expressed on the intact protein. In this report, we describe the production and characterization of rabbit antibodies to isolated H62 and L62 chains to further prove that individual chains express Id62 in an immunogenic form. The results demonstrate that both chains are capable of eliciting antibodies that, after appropriate adsorption, behave like conventional anti-Id62 antibodies prepared against the intact antibody molecule. By direct radioimmunoassay binding, competition of Id binding and Western blot anti-H62 and anti-L62 antibodies identify as Id-positive the same group of IgG1, bind in a reciprocal fashion to H- and L-chains of parental monoclonal antibody 62, and detect Id62-positive polyclonal serum autoantibodies to thyroglobulin. We conclude that monoclonal antibody 62 expresses independently a similar Id on both polypeptide chains and the intact antibody molecule, or its isolated chains, induce qualitatively similar anti-Id responses. These results are discussed in light of the possible structure/function implication such autoantibodies may have within the Id network.

Animals↗

Effects of a cytosolic protein on the interaction of rat pancreatic zymogen granules in vitro.

Photon correlation spectroscopy has been used to study the kinetics of aggregation of isolated rat pancreatic zymogen granules in vitro by monitoring time-dependent changes in mean particle size derived from the photon count autocorrelation function, g2(tau). Isolated granules were stable in isotonic sucrose (pH 5.4-7.0). At pH 6.0 they maintained a mean diameter of 1225 +/- 18 nm with a polydispersity index of 0.199 +/- 0.007. The mean granule diameter showed a limited decrease (approx. 20%) with increasing pH within the range 5.4-7.0, but the polydispersity index was unaltered. At pH greater than 7.0 granule instability was indicated by a rapid reduction in total photon counts. In solutions of monovalent cations ([M+] greater than 10 mM) and divalent cations ([M2+] greater than 0.5 mM) zymogen granules aggregated at a rate dependent upon both ion and granule concentration. These effects were consistent with the bimolecular nature of the interaction mechanism and were clearly distinguishable from the limited size changes associated with osmolarity. At concentrations of Na+ or K+ salts greater than 50 mM granule aggregation was accompanied by anion-dependent solubilisation. A soluble protein fraction separated from the pancreatic acinar cell cytosol by gel filtration reduced the mean diameter and polydispersity index of zymogen granules suspended in isotonic sucrose, inhibited cation-induced aggregation and stabilised granules to solubilisation induced by raising pH greater than 7.0 or exposure to high ionic strength media. The inhibitory effects of this protein were apparent at concentrations less than or equal to 10 micrograms X ml-1 (i.e. at inhibitor: granule protein ratios less than 1:20) and could not be mimicked by bovine serum albumin, the Ca2+-binding proteins calmodulin and troponin C (less than or equal to 100 micrograms X ml-1), nor the highly negatively charged polymer polyglutamate (less than or equal to 10 micrograms X ml-1). Inhibitory activity was also absent from fractions of rat liver cytosol prepared identically to pancreatic acinar cytosol. These observations are consistent with the presence in pancreatic acinar cells of a specific cytosolic granule stabilisation factor (or factors) that normally restricts zymogen granule interaction and may therefore play an important role in the regulation of granule mobility and exocytosis.

Animals↗

Proteus syndrome: an expanded phenotype.

We report on 11 new cases of Proteus syndrome to illustrate the broad range of the phenotype in this hamartomatous dysplasia. The cardinal manifestations of this sporadic disorder are hemihypertrophy, macrodactyly, exostoses, scoliosis, cavernous hemangiomas, lipomas, linear sebaceous nevi, and deeply rugated soles of the feet. Intelligence is usually normal. The differential diagnosis includes Klippel-Trenaunay-Weber and partial lipodystrophy syndromes.

Adolescent↗

Age-related shrinkage of cortically projecting cholinergic neurons: a selective effect.

The number and size of basal forebrain neurons that provide the cholinergic innervation for the cerebral cortex, amygdala, and hippocampus were studied in young and aged mice. The results showed that these neurons became substantially smaller with increasing age. This effect was relatively selective, since the immediately adjacent cholinergic neurons in the striatum did not show a change of similar magnitude. The shrinkage of these basal forebrain neurons may account for the decline of cholinergic innervation that occurs with age. In the material that we examined, aging did not influence the number of cholinergic neurons in the basal forebrain, only their size. It seems, therefore, that the age-related changes in cholinergic function (and their putative behavioral consequences) are not associated with a substantial component of irreversible cell death.

Aging↗

Postanal repair and intersphincteric Ivalon sponge rectopexy for the treatment of rectal prolapse.

Twenty-four consecutive patients (mean age: 74 years) with complete rectal prolapse, fifteen of whom were incontinent of solid stool, have been treated by postanal repair and intersphincteric Ivalon sponge rectopexy. There was no operative mortality, or serious morbidity. There was one recurrence of complete prolapse which occurred 14 days after operation. The other 23 patients have been followed for up to 4 years. All patients who were incontinent of solid stool pre-operatively have been rendered continent. This type of operation may be the treatment of choice in the elderly, where an abdominal procedure is considered unwise and in cases of rectal prolapse associated with faecal incontinence.

Adult↗

Control of secretory granule interaction and exocytosis in pancreatic cells.

Application of the laser-based technique of photon correlation spectroscopy to an in vitro study of the ionic stability and interaction kinetics of zymogen granules isolated from rat exocrine pancreas is described here. In addition the separation from pancreatic acinar cell cytosol of a factor which stabilizes isolated zymogen granules and inhibits cation-induced granule aggregation is outlined. The basis of this action and the significance of the cytosolic inhibitory factor in the regulation of granule mobility and exocytosis in vivo is discussed.

Animals↗

Psychological status of morbidly obese women before gastric restriction surgery.

One hundred and eighteen of 142 morbidly obese women had gastric restriction surgery after completing self-report questionnaire measures of psychosocial adjustment as part of their preoperative psychiatric assessment. Compared with an age-matched normal population, they scored significantly higher on measures of phobic anxiety, somatization, depression, hostility, and marital dissatisfaction, the last being associated mainly with later onset obesity. Factor analysis of questionnaire and weight data showed that weight was largely independent of psychological adjustment, although associations occurred when analysis was restricted to the data on married women, in which marital and self-assertion abnormalities loaded significantly on the same factor.

Adaptation, Psychological↗

Translation of ferritin light and heavy subunit mRNAs is regulated by intracellular chelatable iron levels in rat hepatoma cells.

Acute administration of iron to rats has been previously shown to induce liver ferritin synthesis by increasing the translation of inactive cytoplasmic ferritin mRNAs for both heavy (H) and light (L) subunits by mobilizing them onto polyribosomes. In this report rat hepatoma cells in culture are used to explore the relationship of this response to intracellular iron levels. After adding iron as ferric ammonium citrate to the medium, latent ferritin H- and L-mRNAs were extensively transferred to polyribosomes, accompanied by increased uptake of [35S]methionine into ferritin protein. Because total cellular levels of L- and H-mRNA were not significantly changed by exposure to iron, the increased ferritin mRNAs on polyribosomes most probably come from an inactive cytoplasmic pool, consistent with the inability of actinomycin-D and of cordycepin to inhibit iron-induced ferritin synthesis. When deferoxamine mesylate, an intracellular iron chelator, was added after the addition of iron to the medium, ferritin mRNA on the polyribosomes was reduced, while the free messenger pool increased, and ferritin synthesis diminished. In contrast, the extracellular iron chelator diethylenetriaminepentaacetic acid failed to inhibit the induction of ferritin protein synthesis. Addition of iron in the form of hemin also caused translocation of mRNA to polyribosomes, a response that could be similarly quenched by deferoxamine. Because hemin does not release chelatable iron extracellularly, we conclude that the level of chelatable iron within the cell has a regulatory role in ferritin synthesis through redistribution of the messenger RNAs between the free mRNA pool and the polyribosomes.

Animals↗