Biomedical subjects
R A Wells
Publications and source records attributed to R A Wells.
Metabolic rates in genetically based long lived strains of Drosophila.
The goal of these experiments was to determine if the increased longevity characteristics of our genetically selected long lived line of Drosophila could be attributed to metabolic differences. The data shows an inverse relationship between life span and temperature for both the long lived (L) and normal (R) strains; however, the higher longevity of the L strain relative to the R strain is not affected by these treatments. Therefore, the genetic factors unique to the L strain do not affect the same processes affected by the temperature treatments. A second set of experiments detected a linear relationship between the MDMR (mean daily metabolic rate) and the ambient adult temperature. However, at each temperature, the MDMR of either strain was statistically equivalent; a finding which demonstrates that an increased life span depends on something other than conservation of calories. A third set of experiments looked at the metabolic efficiency of the two strains and were not able to detect any statistically significant differences. The two strains appear to expend approximately equivalent numbers of calories per day in an approximately equivalent manner. These data are interpreted in the context both of a previously postulated genetic switch mechanism believed responsible for initiating the onset of senescence, and of contemporary reinterpretations of the "rate of living" theory which implicates the essential role of various anti-oxidant defense systems.
Prediction of consanguinity using human DNA fingerprints.
DNA fingerprinting was performed to verify the pedigree structure of a family under investigation for an unusual case of beta thalassaemia. A higher than expected proportion of hypervariable bands was shared by the proband and his mother, leading to suspicion that the child had been the product of a consanguineous mating. Further analysis of the mother's brother showed that he was almost certainly the proband's father.
Assessment of clonality in gastrointestinal cancer by DNA fingerprinting.
DNA fingerprinting with three different probes (33.15, 33.6, and alpha-globin 3'HVR) was investigated as a method for the determination of clonality in gastrointestinal tumors. In 29/44 carcinomas the tumor DNA showed clonal somatic mutations that were not seen in the corresponding peripheral blood and normal mucosa samples. The changes consisted of either novel fingerprint bands, losses of bands, or both. The probe 33.15 yielded the highest rate of abnormal DNA fingerprints (21/44 carcinomas). Sequential use of the probes increased the number of cases where clonal fingerprint markers could be detected. One out of five colorectal adenomas also showed a clonal loss of a fingerprint band. In two cases of gastric cancer, DNA from the metastatic tumor had a different DNA fingerprint from that found in the primary carcinoma. DNA fingerprinting offers a novel approach to determining clonality in tumors and may prove useful for the study of tumor progression.
Individual marital therapy: a critical reappraisal.
The belief that individual marital therapy (IMT) is an ineffective form of treatment for marriage problems and markedly inferior to the conjoint approaches has become almost an article of faith in family therapy circles. This position was originally advanced in the influential reviews of the research literature conducted by Gurman and Kniskern, and their conclusions have been cited in numerous other articles. This paper re-reviews the research studies purportedly supporting this conclusion and finds almost all of them to be invalidated by gross flaws in design and implementation. It is argued that from the highly inadequate evidence available, no conclusions can be reached concerning either the absolute or relative effectiveness of IMT.
Parasitologic and immunologic studies of experimental Plasmodium falciparum infection in nonsplenectomized chimpanzees (Pan troglodytes).
Parasitologic, hematologic, and immunologic parameters were monitored in intact (nonsplenectomized), adult chimpanzees infected with a "chimp-adapted" strain of Plasmodium falciparum. Following primary and secondary injections of 10(9) P. falciparum-infected erythrocytes, each chimpanzee developed a low grade parasitemia (up to 1,000/mm3) and maintained the infection without evidence of eliminating the parasites. Hematologic and serum biochemical values, as well as the majority of immunologic parameters tested, remained unaltered in infected chimpanzees. However, 2 weeks after infection T cells from infected chimpanzees demonstrated an enhanced response in vitro to stimulation with the mitogen PHA, and monocyte phagocytic activity for antibody-coated erythrocytes (Fc-mediated phagocytosis) increased significantly. During malarial infection, apes developed a strong T cell proliferative response to P. falciparum antigens and monocytes showed enhanced phagocytic activity for P. falciparum-infected erythrocytes in the absence of immune serum. These results suggest that cellular immune mechanisms, especially macrophage activation, may help control, but not eliminate, P. falciparum malaria in chimpanzees.
Aspects of Northern Irish migration to America: definitions and directions.
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The mutagenicity of a Prudhoe Bay crude oil and its residues from an experimental in situ burn.
Fresh and weathered Prudhoe Bay crude oil as well as residues from its combustion were tested for mutagenicity using strain TA98 in the Ames Salmonella typhimurium/liver microsome test. Because of the toxicity of the oils involved, mutagenic effects were clearly visible only at very low concentrations. All samples were found to be mutagenic, with precipitated plume having the greatest activity followed by the burn residue, the weathered oil, and fresh crude, respectively. The most polar components of the neutral fraction of the samples displayed the greatest mutagenicity.
Characterization of cold reactive lymphocytotoxic antibodies in malaria.
Characterization of cold reactive lymphocytotoxic antibodies present in sera from Thai adults with malaria revealed that the antibodies are predominantly 19S (IgM), directed against both autologous and allogeneic mononuclear cells, complement-dependent, present in titres ranging from 1:2 to 1:16, and exhibit greater lymphocytotoxic activity during the acute stage of malarial infection than during the convalescent stage. The lymphocytotoxic antibodies were primarily directed against B cell targets or both B as well as T cell targets. In addition some sera were reactive with enriched monocyte/macrophage indicator cells at 15 degrees C, but not 37 degrees C. Antibodies directed against B cell targets were lymphocytotoxic both at 15 degrees C as well as 37 degrees C. The results indicate that IgM lymphocytotoxic antibodies in the sera of patients with malaria are directed primarily against B cells with reactivity to a lesser extent against T cells and macrophages and thus may play an immunoregulatory function in the humoral immune response to malaria infection.
Tempests, teapots (and research design): rejoinder to Stanton and Todd.
Four major issues raised in Stanton and Todd's critique are discussed. These comprise: (a) the inclusion criteria of the review; (b) statistical procedures and research design; (c) the alleged bias of the reviews; and (d) design problems in Stanton and Todd's own study.
Kinetics of peripheral blood leukocyte alterations in Thai children with dengue hemorrhagic fever.
Peripheral leukocytes from 16 Thai children with dengue hemorrhagic fever were examined to determine the leukocyte composition on the day of presentation and on convalescent days 15 and 30. Mononuclear cells were isolated each time, and the concentrations of T, B, Fc receptor-bearing, and "null" cells were determined. On the day of hospitalization, in comparison to convalescent values, there was a significant increase in total lymphocytes, primarily due to concentrations of atypical lymphocytes. There was a significant loss of T cells with an increase in non-T, non-B, non-Fc receptor-bearing null cells. There were no changes in the concentrations of monocytes, B cells, or Fc receptor-bearing cells when acute and convalescent values were compared. During the convalescent period, a progressive increase in eosinophils was noted. Also, on day 15 but not on day 30 of the convalescent period, an increase was observed in the total leukocyte number due to an increase in granulocytes. There results indicate that in Thai children with dengue hemorrhagic fever, there are major shifts within several component cell subpopulations of the immune system.
Examination of peripheral blood mononuclear cells and sera from Thai adults naturally infected with malaria in assays of blastogenic responsiveness to mitogenic lectins and allogeneic cell surface antigens.
We have previously observed that Thai adults who are infected with malaria have a loss of peripheral blood T cells, and that patient sera contain lymphocytotoxic antibodies. In the present study, we examined peripheral blood mononuclear cells from Thai adults naturally infected with Plasmodium falciparum and Plasmodium vivax for the capacity to undergo blastogenesis in response to phytohemagglutinin, concanavalin A, pokeweed mitogen, and allogeneic cell surface antigens in a one-way mixed leukocyte reaction. In addition, sera from actively infected patients were examined with regard to suppressive capabilities toward normal lymphocyte blastogenesis by using the same assays. We found that patient mononuclear cells exhibited normal reactivity to phytohemagglutinin, concanavalin A, and pokeweed mitogen when compared with controls. However, peripheral blood mononuclear cells from patients had a decreased stimulatory capacity in the allogeneic mixed leukocyte reaction, and P. vivax, but not P. falciparum, lymphocytes exhibited decreased responsiveness in the mixed leukocyte reaction. Furthermore, sera from patients with active malaria induced decreased responsiveness by normal mononuclear cells to phytohemagglutinin and concanavalin A, but not pokeweed mitogen; pooled P. falciparum sera caused decreased responsiveness to allogeneic cell surface antigens in the mixed leukocyte reaction. These studies indicate that despite the lost of circulating T cells during the course of infection with malaria, blastogenic responsiveness remains intact, and that sera from patients with malaria are capable of exerting negative immunoregulatory effects.
Anti-lymphocytotoxic antibodies in sera of Thai adults infected with Plasmodium falciparum or Plasmodium vivax.
Because of the potential for the elimination of lymphocytes through anti-lymphocytotoxic antibodies we examined individual sera of patients infected with falciparum or vivax malaria for the presence of antibodies against normal peripheral blood mononuclear cells. In assays done at 15 degrees C, 95% of the P. falciparum patients and 98% of the P. vivax patients showed evidence for antibody activity. Activity at 37 degrees C was significantly less than that at 15 degrees C. These studies suggest that infection with malaria induces anti-lymphocytotoxic antibodies which are predominantly cold-reactive. It is possible that this phenomenon plays a role in modulating the immune response of patients toward malaria.
Loss of circulating T lymphocytes with normal levels of B and 'null' lymphocytes in Thai adults with malaria.
Peripheral blood mononuclear cells from forty-nine Thai adults infected with either Plasmodium falciparum or Plasmodium vivax were examined in order to determine the percentage of T, B, and Fc-receptor-bearing cells present. In comparison to healthy controls, both the percentage and concentration of peripheral T cells were decreased in the malaria-infected individuals as assessed by formation of rosettes with sheep red blood cells. The percentage of peripheral B cells was increased but their concentration was unchanged, as assessed by two techniques: the presence of surface immunoglobulin and the presence of a complement receptor. Both the percentage and concentration of lymphocytes bearing Fc receptors were unchanged in infected individuals. Finally, calculation of the changes in 'null' cells (defined either as non-T, non-B lymphocytes or as non-T, non-B, non Fc-receptor-bearing lymphocytes) revealed an increase in the 'null' cell percentage but a decrease in the absolute number of 'null' cells. These data indicate that in adult Thai patients naturally infected with malaria, there is a real loss of circulating T lymphocytes with no real change in B, Fc-receptor-bearing, or 'null' lymphocytes.
The results of family therapy revisited: the nonbehavioral methods.
Studies from 1971 to 1976 reporting on the outcome of the nonbehavioral family therapies are analyzed and critically reviewed. Such research has increased in both quality and quantity since 1970 and, broadly speaking, has legitimized the status of family therapy as a viable mode of helping. Particularly potent effects were noted for family therapy as an alternative to psychiatric hospitalization, with psychosomatic problems in children and adolescents, and in certain applications with parent-child and parent-adolescent relationships. However, a number of studies comparing family therapy with no formal treatment or an alternative treatment found little difference in outcome. Problems in family therapy outcome research are discussed and some future directions suggested.
Ideologies, idols (and graven images?): rejoinder to Gurman and Kniskern.
Three major issues raised in Gurman and Kniskern's commentary are discussed. These are (a) the suitability of established research design criteria for studying the outcome of family therapy; (b) the impact of therapist relationship factors on therapy outcome; and (c) the place of concrete or objective change measures in psychotherapy outcome research. Areas of agreement and disagreement with Gurman and Kniskern's observations are identified.
Plasmodium yoelii: an inbred model for protective immunization against malaria in BALB/c mice.
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Structured, short-term multiple family therapy: an educational approach.
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