Nurse and patient: allies preventing amputation (continuing education credit).
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Amputation, Surgical↗
Biomedical subjects
R A Miller
Publications and source records attributed to R A Miller.
Heterogeneity among T helper cells. Interleukin 2 secretion and help for immunoglobulin secretion.
T lymphocytes are thought to provide "help" for B cells by activating them from the resting state, by secretion of antigen-nonspecific lymphokines that promote B cell differentiation and maturation, and by providing signals that induce isotype switching. To clarify the extent to which these different forms of helper activity could be carried out by individual T cells, we set up cultures in which B cells activated, and were in turn themselves stimulated by, limiting numbers of T cells through differences at the H-2 or Mls loci. At T cell doses at which responses were likely to represent the activity of individual helper T cells (or their immediate clonal progeny), we found that some T cells were able both to produce interleukin 2 (IL-2) and to induce secretion of both IgM and IgG, whereas others induced immunoglobulin (Ig) secretion without detectable IL-2 production, and still others made IL-2 but did not promote antibody secretion. We could not detect B cell stimulatory factor 1 production by alloantigen-stimulated T cells, and the addition of antibodies to B cell stimulatory factor 1 did not prevent Ig production. Two results, however--higher Ig accumulation in those wells that received an IL-2-producing cell, and inhibition by anti-IL-2 receptor antibodies of B cell but not T cell function--are consistent with a direct stimulatory effect of IL-2 on B cells in this system. The pattern of helper functions exhibited by T cells freshly isolated from mice differs from that inferred from studies of cloned lines of T cells in long term cultures.
Animals↗
Functional T cell deficits after bone marrow transplantation across minor histocompatibility barriers: effects of graft-vs-host disease on precursor frequency of reactive cells.
We have studied T cell responses in mice transplanted with bone marrow from H-2-identical, minor histocompatibility loci-nonidentical donors (B10.BR----CBA) in which graft-vs-host disease is induced by the addition of donor T cells. T cell responses to mitogen were examined both in high density, conventional bulk cultures and by limiting dilution analysis. Long-lasting deficits in the frequency of functional T cells were observed, for both IL 2-producing and cytotoxic cells, in proportion to the severity of the graft-vs-host disease induced. These deficits did not reflect a corresponding loss of Thy-1+ cells nor a loss of function in conventional cultures in mice studied at later times after bone marrow transplantation. These deficits in reactive cells are not completely correctable with IL 2, and provide further insight into the nature of T cell reconstitution of the immune system after bone marrow transplantation.
Animals↗
Suppression of anti-mouse immunoglobulin antibodies in subhuman primates receiving murine monoclonal antibodies against T cell antigens.
Murine monoclonal antibodies stimulate the production of human anti-mouse immunoglobulin antibodies (AMIA) when administered to patients. This limits their long-term usefulness as therapeutic and diagnostic agents. We report the use of three maneuvers to suppress AMIA against T cell-specific monoclonal antibodies in cynomolgus monkeys. Twelve monkeys received daily i.v. infusions of 1 mg each of anti-Leu-2a, -3a, and -5 on days 1 through 10. One group (control) received no suppressive regimen. The second group received cyclosporine, 12.5 mg/kg daily on days -7 to +14. The third group (PI) were passively immunized with 0.4 ml of hyperimmune monkey AMIA serum on days -7, -1, 2, 4, 6, and 8. The fourth group (TLI) received 1700 rad fractionated total lymphoid irradiation ending on day -1. The animals treated with TLI were markedly delayed in the onset of AMIA, which was suppressed to less than 1% of the control group. The AMIA specific for the constant region of animals receiving PI was also suppressed to one-third of control. The majority of the AMIA in all the animals was anti-idiotypic and wholly anti-idiotypic in the TLI animals.
Animals↗
Diminished calcium influx in lectin-stimulated T cells from old mice.
T lymphocytes from aged donors function poorly, but the biochemical basis for the defect remains uncertain. We tested the hypothesis that T cells from old mice had a diminished ability to transmit extracellular signals into the cytoplasm, by measuring intracellular free calcium concentrations (Cai) in T cells stimulated by the polyclonal activator concanavalin A (Con A). Using the second-generation fluorochrome indo-1 as a reporter of Cai, we found that the Con A-induced elevation of Cai levels is reduced both in rate and extent in old T cells, as compared to T cells from young mice. Flow cytometric analysis showed that this age-sensitive change represents a decline, with age, in the number of T cells that can respond to Con A by increasing their Cai above resting baseline levels (100-120 nM). These results thus show that defects in activation are manifested by T cells from old donors within the first 5 minutes of the activation process, and suggest that aging may lead to alterations either in the surface molecules that receive extracellular signals, or in the sequence of coupled events by which these extracellular signals bring about alterations in the intracellular ionic milieu.
Aging↗
Effects of subchronic inhalation exposure of mice to a high-boiling coal liquid.
Mice (CD-1) were exposed to aerosol concentrations of 0.0, 0.03, 0.14, or 0.69 mg/liter of heavy distillate (HD), a high-boiling coal liquid from the solvent-refined coal (SRC)-II process. Exposures were for 6 hr/day, 5 days/week for 13 weeks. Particle sizes ranged between 1.6 and 1.8 micron, mass median aerodynamic diameter, with a geometric standard deviation range of 1.9-2.5. Growth for high-dose males was significantly less than that of the control group. Compared to controls, weights of liver were significantly higher and those of ovaries and thymus significantly lower; these changes were significant on both absolute and relative weight bases. The number of red blood cells, volume of packed red cells, and hemoglobin concentration for animals from the high-dose group were significantly lower than those of controls. Microscopic examination of organ sections showed focal hepatic necrosis and nonspecific hepatopathy. Additionally, olfactory epithelial degeneration occurred in a dose-dependent manner. Results from this study indicated that exposure to HD caused adverse effects at the high dose and that these changes were either less severe or absent in middle-dose group mice. Comparison of these results with those for rats indicated that with rats the biological effects were more severe and present at lower doses than was observed for mice.
Administration, Inhalation↗
Exacerbated spinal neurologic deficit during sedation of a patient with cervical spondylosis.
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Aged↗
Computer-based diagnostic decisionmaking.
The three decisionmaking aids described by the authors attack the generic problem of "see no evil, hear no evil, speak no evil"--improving the detection, diagnosis, and therapy of psychiatric disorders in the primary care setting. The three systems represent interventions at different steps in the process of providing appropriate care to psychiatric patients. The DSPW system of Robins and Marcus offers the potential of increasing the recognition of psychiatric disease in the physician's office. Politser's IDS program is representative of the sort of sophisticated microcomputer-based decisionmaking support tools that will become available to physicians in the not-too-distant future. Erdman's study of the impact of explanation capabilities on the acceptability of therapy recommending systems points out the need for careful scientific evaluations of features added to diagnostic and therapeutic systems.
Decision Support Techniques↗
The integrated cystoscope: an alternative to conventional and fibreoptic cystoscopy.
This report describes a new integrated rigid cystoscope which has been designed for diagnostic and therapeutic cystoscopy under local anaesthesia. The small external diameter (17.5 F) and large instrument channel permit maximum irrigant flow and operating potential whilst causing minimum discomfort to the patient. We believe this instrument to be a practical alternative to conventional cystoscopes, including the fibreoptic cystoscope.
Cystoscopes↗
Extracorporeal shock wave lithotripsy. Is sessional access worthwhile?
One hundred and fifty-three patients with renal stones referred to one teaching hospital have received extracorporeal shock wave lithotripsy (ESWL) treatment as a result of a monthly sessional arrangement organised with a neighbouring lithotripter unit. The results of treatment, assessed 3 months after lithotripsy, showed results comparable with those from any lithotripter centre. Sessional access for lithotripsy may provide a satisfactory way of increasing the number of patients who are treated with lithotripsy by reducing the demand for beds at the hospitals where a lithotripter is sited.
Adolescent↗
From automated medical records to expert system knowledge bases: common problems in representing and processing patient data.
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Data Collection↗
Studies on B lymphoid tumors treated with monoclonal anti-idiotype antibodies: correlation with clinical responses.
Monoclonal anti-idiotype antibodies can be made which are exquisitely specific for B lymphocytic malignancies. We have conducted a clinical trial in which some patients' tumors regressed after infusion of such antibodies. Here, we evaluated characteristics of the antibodies, the tumors, and the patients to determine which features best correlated with the clinical response. Neither the isotype of the murine antibodies, nor their avidity were predictive of clinical outcome. The specific epitope to which the antibodies bound was characterized by immunochemical techniques. Reactivity with a heavy-light chain combinatorial determinant correlated somewhat with clinical effect. Variations in the characteristics of the individual tumors such as antigen sites per cell and ability to modulate the surface immunoglobulin were not predictive of response. In one patient with prolymphocytic leukemia the anti-idiotype antibody had a direct antiproliferative effect on tumor cells in vitro. This patient's tumor response was explainable by such a direct mechanism. In the other patients, who had lymphomas, therapeutic outcome correlated with the number of host nontumor cells infiltrating the tumor. The vast majority of these nontumor cells were mature T lymphocytes of the Leu 4, Leu 3 (T3, T4) phenotype. Thus, a preexistent host-tumor interaction seems to be important in the in vivo effect of anti-idiotype antibodies in B cell tumors.
Antibodies, Anti-Idiotypic↗
Decreased hematopoietic accessory cell function following bone marrow transplantation.
Hematologic engraftment following bone marrow transplantation requires not only pluripotent stem cells but also functioning accessory cells whose trophic factors support the proliferation and differentiation of stem cells and progenitors to mature blood cells. To better understand the regulation of hematopoiesis following transplantation, we studied hemopoietic accessory cell function in bone marrow transplant recipients 3 weeks to 10 months following transplantation. In general, hematopoietic accessory cell function was decreased following bone marrow transplantation. Sequential fractionation of accessory cells demonstrated that adherent cells often produced near-normal functional burst-promoting activity (BPA) and granulocyte-macrophage colony-stimulating activity (GM-CSA), but Fc receptor-positive (Fc+) cells and T cells uniformly produced greatly reduced BPA and GM-CSA, as compared to transplant donor cells. This cellular deficiency was corrected by soluble burst-promoting activity and granulocyte-macrophage colony-stimulating activity and so appeared to be due to the failure of accessory cells to produce trophic hormones. Limiting-dilution analysis (LDA) for proliferating T-cell precursors demonstrated a greatly reduced frequency in phytohemagglutinin-responsive cells, supporting the role of deficient hematopoietic growth factor production by activated T cells in transplant recipients. This hemopoietic accessory cell defect may thus reflect more generalized lymphocyte dysfunction in these patients. Hematopoiesis following bone marrow transplantation appears to rely upon growth factors released by accessory cells in the adherent layer.
Adolescent↗
In vitro tests that predict tumor-associated idiotype levels in the serum of patients with B cell lymphomas and leukemias.
The presence of circulating tumor idiotype interferes with the in vivo effectiveness of anti-idiotype antibodies. We developed two assays that permit identification of patients with high levels of serum idiotype without the need for first producing an anti-idiotype antibody. A cell suspension made from the tumor was cultured for seven days with or without phytohemagglutin (PHA) and/or phorbol myristic acetate (PMA). Ig secretion in vitro by patients' tumor cells varied. In 4 patients, no secretion in vitro occurred, 5 patients had low levels, and 5 patients had high levels of Ig secretion. In three patients, Ig secretion occurred only after stimulation with PHA, PMA, or both. Spontaneous or induced immunoglobulin secretion in vitro is related to the levels of tumor idiotype secretion that exist in vivo. Eight patients with serum idiotype levels greater than 100 micrograms/mL (mean 265 micrograms/mL), had a minimum of 1.0 microgram/10(6) cells of idiotype secretion in vitro. Nine patients with serum idiotype levels less than 30 micrograms/mL (mean 3.7 micrograms/mL), had less than or equal to 0.5 microgram/10(6) cells of idiotype secretion in vitro. In another assay, the levels of IgM kappa and IgM lambda in patients' sera were compared with those in normal serum. An imbalance in the relative amounts of IgM kappa and IgM lambda indicated high levels of circulating idiotype in the serum, but this assay was less sensitive than the in vitro secretion assay and limited to IgM-secreting tumors. These assays will be useful for future clinical studies using anti-idiotype antibodies.
Antibodies, Anti-Idiotypic↗
Medical Subject Headings and medical terminology: an analysis of terminology used in hospital charts.
Terminology used by health professionals in everyday written discourse was compared with terminology in a standardized medical vocabulary, the Medical Subject Headings (MeSH). Fifty written hospital charts were selected at random and analyzed by a computer program that identified MeSH terms in the charts. The charts were analyzed against two related MeSH vocabularies--one containing MeSH terms and one containing both MeSH terms and backwards cross-reference terms. When small words such as articles and prepositions were disregarded, approximately 50% of the words in a medical chart were found to be MeSH-related terminology. In addition, about 40% of MeSH-related words in the charts were either MeSH terms or backwards cross-reference terms.
Hospital Records↗
Retarded recovery of functional T cell frequencies in T cell-depleted bone marrow transplant recipients.
We have studied the effect of removing donor T cells by treatment with the monoclonal antibody Leu-1 and complement before marrow transplantation on the regeneration of functionally competent T lymphocytes in the blood at selected times after transplant. Using sensitive limiting-dilution methods that allow us to enumerate helper, cytotoxic, and proliferating T lymphocyte precursors, we report that regeneration of a functional T cell compartment is more severely impaired for the first 180 days after transplantation in those patients given T cell-depleted bone marrow than in recipients of untreated marrow. After this first 6 months, however, patients given T cell-depleted bone marrow had blood T cell frequencies comparable to those observed in patients given untreated marrow. Diminished frequencies of reactive T cells in recipients of depleted marrow could leave them more susceptible to infection or to the recurrence of neoplastic cells.
Bone Marrow Cells↗
Treatment of chronic erythema nodosum leprosum with cyclosporine A produces clinical and immunohistologic remission.
We have treated three leprosy patients suffering from chronic, steroid-dependent erythema nodosum leprosum (ENL) with cyclosporine A (CsA). Excellent results were obtained in two patients. Extra-cutaneous manifestations of the reactional state were completely suppressed, and the development of new skin lesions was sharply curtailed. Immunohistologic abnormalities characteristic of active ENL were corrected. Lymphocyte subpopulations and anti-mycobacterial antibody levels in peripheral blood were unaffected. The third patient showed only a partial response to CsA, but satisfactory blood levels were never obtained in this individual because of dose-related gastrointestinal toxicity. The effectiveness of CsA in the treatment of ENL is consistent with the hypothesis that aberrant activation of a subset of T-helper cells is involved in the pathogenesis of this reaction. CsA may have a role in the treatment of chronic ENL that has failed to respond to conventional therapeutic modalities.
Adult↗