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Biomedical subjects

L Palmer

Publications and source records attributed to L Palmer.

At least 91 records · Page 5Linked to original sources
PubMed1983

Host recognition of fetal antigens: do they induce specific antibodies?

The purpose of this study was to ascertain whether the protection afforded to adult mice against the induction and growth of 3-methylcholanthrene-induced tumours by prior exposure to syngeneic fetal cells has an immunological basis. Adult CBA mice were inoculated with fetal cells according to a variety of protocols and the sera were tested for their ability to bind to fetal and adult tissue cells, using a staphylococcal protein A binding assay. All 10 sera tested showed some degree of binding though this varied from strong to weak, and there was some cross-reactivity with adult thymic cells but relatively little with adult spleen cells. Absorption studies were carried out with one of these sera and with two others raised against testicular and thymic cells, respectively. The absorption patterns obtained so far suggest that fetal cells possess at least three, and possibly up to five, distinct antigens. Although none of the anti-fetal sera were produced with a sensitizing protocol identical with that used in in vivo protection, some of them were so close as to suggest that protection is associated with, and perhaps causally related to, these IgG antibodies. The in vitro evidence presented here, together with the in vivo data of P. B. Medawar & R. Hunt, shows that antigens are shared between fetal cells and adult thymic and testicular cells. It therefore lends support to the notion that the production of a vaccine against anaplastic neoplasms, using immunogens derived from adult tissues, is within the realms of possibility.

Animals↗
PubMed1983

Enhancement of specific antitumor immunity in mice fed a diet enriched in vitamin A acetate.

Age-matched male CBA mice on a conventional or a vitamin A acetate (VAOAc)-rich diet were immunized with irradiated cloned 3-methylcholanthrene- or Harvey sarcoma virus-induced (McSa-1 or HT3-2.1) sarcoma cells and then challenged with viable corresponding or unrelated (non-crossreacting) syngeneic sarcoma cells. The survival of the specifically immunized mice on the VAOAc diet was significantly prolonged in comparison with all control groups of mice as assessed by using logrank tests. Moreover, the specific immunization markedly decreased the incidence of tumors after the McSa-1 (but not HT3-2.1) challenge in a group of mice on the VAOAc diet (5% tumor incidence) compared with the equivalent group on the control diet (50% tumor incidence). Neither the VAOAc diet nor in vivo immunization alone or combined influenced natural killer cell activity. Specific T-cell-mediated cytotoxicity after in vivo priming and in vitro boosting with sarcoma cells was increased in VAOAc-fed mice. However, the marginal increase in cytotoxicity does not in itself explain the strikingly increased resistance to tumor transplants in preimmunized mice on the VAOAc diet in comparison with preimmunized mice on the control diet. The results indicate that a diet enriched in VAOAc can modify the ability of the immune system of a mouse to respond effectively to tumor antigens and can influence whether a tumor grows or regresses.

Animals↗
PubMed1982

Nonsense suppression in aminoacyl-t-RNA limited cells.

A number of nonsense alleles of lacZ exhibit phenotypic suppression (as much as a sixteen-fold increase in leakiness) during partial limitation for certain aminoacyl-tRNA species in relA mutant cells. Each responsive allele has its individual pattern of response to limitation for one or more amino acids or aminoacyl-tRNA's. The phenotypic suppression occurs only during limitation, and ceases once limitation is reversed. Suppression is much reduced by the presence of the relA+ allele or an allele of rpsL which restricts ribosomal ambiguity. In one case, the suppressed product has been identified by radioimmune assay and gel electrophoresis, and is a full-length lacZ protomer. Mechanisms are discussed whereby aberrations of translation at codons calling for an aminoacyl-tRNA species in short supply might lead to readthrough of a nearby nonsense codon.

Escherichia coli↗
PubMed1981

Late results of initially-successfully vitrectomy in diabetes.

Long-term follow-up of 135 eyes that had initially-successful vitreous surgery for complications of proliferative diabetic retinopathy indicates that most of these eyes remain visually and anatomically stable and do not develop new retinal neovascularization. The nature and incidence of important complications during the early and later postoperative periods are discussed.

Diabetic Retinopathy↗
PubMed1979

Error propagation in viable cells.

Error propagation is the process, predicted by theoretical models, whereby errors in translating the genetic code will beget fresh errors in successive generations. It has been postulated that error propagation may underly the mortality of cells which display clonal senescence. We have demonstrated the occurrence of error propagation in viable cells of E. coli during growth in a low concentration of streptomycin, a drug which promotes ribosomal ambiguity. We monitored error propagation by measuring mistranslation of a specific UAA codon, and measured viability by direct enumeration of both live and dead cells through a sensitive microscopic technique. We find that the error frequency may be artificially increased by at least an order of magnitude without generating any detectable increase in the proportion of dead cells or of cells whose descendents are doomed to clonal senescence. The error frequency increases gradually over the course of a few generations, in qualitative agreement with the notion of error propagation, and eventually stabilizes at a constant value much higher than normal. The kinetics of this increase agree quantitatively with the Hoffman-Kirkwood and Holliday formulation of error propagation, for parameter values which dictate convergence to a stable error frequency. This convergent behaviour, under conditions of enhanced mistranslation, demonstrates that the normal parameters are well removed from the region of instability in error propagation; even an order of magnitude increase in mistranslation does not tip the translation system into the unstable mode which has been postulated to underly cell senescence. Thus, the error catastrophe theory of cell senescence cannot apply to the translation system of bacteria. We have reviewed experimental data on the fidelity of translation in somatic cells of higher organisms which militate against the notion that the translation system in these cell types could be much closer to the region of instability than in bacteria. These considerations controvert the error catastrophe theory of cell senescence.

Alkaline Phosphatase↗
PubMed1979

Regulatory nucleotides involved in the Rel function of Bacillus subtilis.

We have examined the accumulation of polyphosphorylated nucleotides in Bacillus subtilis in relation to the function of the rel gene. Our results are as follows. (i) During inhibition of isoleucine activation by O-methylthreonine, wildtype B. subtilis cells accumulate unusual nucleotides with the chromatographic and chemical properties of pppApp, ppApp, pppGpp, ppGpp, pGpp, and ppGp. (ii) During the carbon source downshift elicited by inhibiting glucose uptake, we observed accumulation of the polyphosphorylated guanosine but not adenosine nucleotides. (iii) At the end of long phase in sporulation medium, we observed a small transient accumulation of the polyphosphorylated guanosine but not adenosine nucleotides. (iv) We were unable to detect a nucleotide with chromatographic behavior expected for pppAppp under any conditions. (v) The rel mutant of Swanton and Edlin (Biochem. Biophys. Res. Commun. 46-583-588, 1972) did not accumulate any of these polyphosphorylated nucleotides under any of the conditions examined. (vi) the rel mutant is unimpaired in sporulation. We conclude that one or more of the nucleotides we have detected may be involved in controlling the specificity of transcription during the stringent response, but none of them are required for sporogenesis.

Adenine Nucleotides↗
PubMed1977

Anomalous synthesis of ppGpp in growing cells.

In E. coli cells, accumulation of ppGpp is normally triggered by conditions that restrict the aminoacylation of tRNA or interfere with carbon/energy source metabolism; in both cases, the nucleotide's accumulation is associated with control of stable RNA synthesis and is generally believed to bring it about. We have found an anomalous situation wherein vigorously growing cells accumulate a high level of ppGpp and there is no restriction of stable RNA synthesis. This occurs when wild-type cells are shifted up from an abnormally low growth temperature to one in the optimal range (35 degrees C-40 degrees C). The effect is partly, but not entirely, dependent upon the presence of a functional relA gene product. These results appear to call into question the simpler interpretations of the role of ppGpp in the control of stable RNA synthesis.

Amino Acids↗
PubMed1976

Gastric acid responses to graded i.v. infusion of pentagastrin and histalog in peptic ulcer patients before and after antrum-bulb resection.

Gastric acid responses to graded i.v. infusion of pentagastrin and Histalog were determined in peptic ulcer patients. Single-day multiple-dose tests were performed. The sensitivity to the humoral stimuli as determined by the calculated ED50's was not significantly different for duodenal ulcer patients with moderate (DUmod) or massive (DUmass) observed hypersecretion or for gastric ulcer (GU) patients: median ED50's of pentagastrin were 6.2, 6.6, and 13.1 mug/h in 18 DUmod, 22 DUmass and 7 GU patients respectively, and median ED50's of Histalog were 16.6, 25.3, and 17.1 mg/h in 14 DUmod, 10 DUmass and 6 GU patients respectively. Antrum-bulb resection significantly reduced basal acid secretion and maximal acid responses to the humoral stimuli (about 45% reduction) but did not significantly change the loss of gastric contents to the intestine or the sensitivity to the humoral stimuli (median ED50 of pentagastrin increased from 5.2 to 6.7 mug/h in 14 patients, and median ED50 of Histalog increased from 16.0 to 20.8 mg/h in 12 patients), suggesting that the intact antrum-bulb region of the ulcer patient is controlling the capacity to secrete acid, and indicating that antrum-bulb gastrin is an important trophic factor for the parietal cells in man.

Betazole↗