Immunology of the Acquired Immunodeficiency Syndrome

The Acquired Immunodeficiency Syndrome (AIDS) first recognized in 1981, has been extensively studied, and the most recent studies have demonstrated that its defects extend well beyond the apparent deficient cell-mediated immunity to include humoral immunity, autoimmunity, and abnormal immunoregulation. The recent discovery of a retrovirus, HTLV III, as a possible etiologic agent is discussed in relation to other viruses known to cause immunodeficiency. Simian AIDS, an animal model of virus-induced immunodeficiency, is also discussed. Recommendations are made regarding the interpretation and limitations of immune testing in AIDS, including a discussion of how apparently healthy homosexuals and groups at risk develop an immunologic profile which mimics that of patients with AIDS

Eosinophilic and neutrophilic leukemoid reaction in a woman with spindle cell sarcoma: a case report

<p>Abstract</p> <p>Introduction</p> <p>We report a case of a patient with marked eosinophilia and neutrophilia as a manifestation of a spindle cell sarcoma.</p> <p>Case presentation</p> <p>A 41-year-old African American woman presented with an enlarging, painful mass in her right knee area. Four years previously, she had had a mass similar to this diagnosed as an osteosarcoma, and had undergone a radical resection and hinge-knee replacement. Before the surgery, she was treated with neoadjuvant docetaxel and gemcitabine. A biopsy was taken from the recurrent mass, and histological examination revealed high-grade soft-tissue sarcoma. The patient received no further treatment. Complete blood counts revealed a white blood cell (WBC) count of 13.6 to 17.9 × 10⁹/L, with neutrophils being 8.2 to 10.9 × 10⁹/L and eosinophils 1.8 to 1.9 × 10⁹/L. At readmission six months later, WBC was 126.7 × 10⁹/L, with neutrophils being 57.02 × 10⁹/L and eosinophils 60.82 × 10⁹/L. The eosinophils peaked at 77.79 × 10⁹/L two days later. Evaluations for allergies, infection, and autoimmune mechanisms were negative. Bone marrow revealed increased eosinophils without blasts. After resection, blood counts abruptly decreased to the normal range. Pathology confirmed high-grade spindle cell sarcoma. Approximately one year after resection, the patient was readmitted with metastatic disease to her lungs. During this presentation, her eosinophil and neutrophil count was again increased. WBC was 107.8 × 10⁹/L, with eosinophil count of 47.43 × 10⁹/L and neutrophil count of 44.10 × 10⁹/L. Interleukin-5 was normal, and granulocyte–macrophage colony-stimulating factor (GM-CSF) was elevated at 208.8 (normal < 4.8).</p> <p>Conclusion</p> <p>In our case, the patient had eosinophilia and neutrophilia associated with a spindle cell sarcoma, possibly representing a paraneoplastic syndrome secondary to GM-CSF. There were no signs of infectious, allergic, or autoimmune causes for the eosinophilia or neutrophilia. Even though the occurrence of eosinophilia and neutrophilia with malignancy is rare, patients who have either condition without an apparent cause should be checked for malignancy.</p

Antiherpesvirus Activity in Human Sera and Urines after Administration of Adenine Arabinoside: IN VITRO AND IN VIVO SYNERGY OF ADENINE ARABINOSIDE AND ARABINOSYLHYPOXANTHINE IN COMBINATION

The minimum inhibitory concentration (MIC) of adenine arabinoside (ara-A) in rabbit kidney microtiter tissue cultures (RK-13) to a prototype strain of herpes simplex virus, type 1 (E115) based upon inhibition of cytopathic effects is 1.5 μg/ml. In this system, the MIC of arabinosylhypoxanthine (ara-Hx), the major in vivo metabolic derivative of ara-A, is 75 μg/ml. Inhibition of cytopathic effects of herpes simplex virus, type 1 (HSV-1) in microtiter wells of RK-13 cells varies directly with the concentrations of ara-A or ara-Hx, and inversely with residual HSV-1. The MIC of ara-A for HSV-1 in RK-13 cells is 5-20 times lower than similar measures with vero renal, mouse embryo, or human foreskin cultures. With RK-13 tissue cultures in microtiter plates, an assay for “ara-A equivalents” in human body fluids was developed which compares in sensitivity with high pressure liquid chromatography and has the advantage of simultaneously measuring combined antiherpesvirus effects of ara-A and its major metabolic derivative, ara-Hx. In vitro checkerboard studies in RK-13 cells confirmed that ara-A and ara-Hx in combination had antiviral effects which are synergistic. The total of the fractional MIC of ara-A plus ara-Hx in combination also varies inversely with residual HSV-1 in microtiter wells. Because virus adsorption is complete at 2 h before specimens to be tested are added in this assay, and because human interferon is not measured in rabbit cells, the antiviral assay is not affected by the presence of type-specific antiherpesvirus antibody or human interferon. Antiviral activity (AVA) was assayed as ara-A equivalents in sera and urines from 10 patients with serious herpesvirus infections who received 2.5-20 mg/kg daily of ara-A by intramuscular or intravenous routes. When a dosage schedule of 10 mg/kg per day or more was used, sustained concentrations of AVA that ranged from 0.8 to 14.4 μg/ml were found. When an inhibitor of adenosine deaminase (covidarabine) was not added to the specimens, mean serum concentrations were ≅3.0 μg/ml (10 mg/kg per day, i.v.), and 4.1 μg/ml (20 mg/kg per day). However, in a single patient given 20 mg/kg of ara-A daily with covidarabine immediately added to the sera, the mean concentration of AVA was 12.9 μg/ml. Urines contained even higher AVA. Assays of 19 sera were performed both by microbiologic assay for AVA and by high pressure liquid chromatography for ara-A and ara-Hx. AVA was greater by microbiologic assay, and was greater than that which could be accounted for by stoichiometric chromatographic measures of ara-A and ara-Hx. These results with sera of treated patients are consistent both with the in vitro synergy of ara-A and ara-Hx found by checkerboard titrations, and with the beneficial responses to ara-A of patients with herpesvirus infections reported here and elsewhere