IMMUNE AND NATURAL ANTIBODIES TO SYNGENEIC MURINE PLASMA CELL TUMORS

Cytotoxic antibody to a plasma cell tumor antigen was produced in syngeneic BALB mice by immunization with viable or inactivated plasma cell tumors. Antibody with the same specificity was found in the sera of normal BALB and other strains of mice. This natural antibody reacted with an antigen with characteristics indistinguishable from the previously described alloantigen, PC.1, and with viral envelope antigen, χVEA. The incidence of cytotoxic reactivity and the antibody titers reached a peak in normal BALB mice at 3–4 months of age, and were lower in 9–12-month old mice. The sera of germfree mice had lower reactivity; but when the mice were transferred to conventional conditions, their sera soon became as active as those of conventional mice. A virus common to all plasma cell tumors, which is present in latent form in some normal tissues of BALB and other PC.1 positive strains, is suggested as the cause for the PC.1 antigen and for the appearance of natural antibody to it. The considerable evidence for the close association of a virus with plasma cell tumors is presented

Modulation of immunity by macrophages

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22754/1/0000309.pd

Inhibition of rat mixed lymphocyte cultures by suppressor macrophages

Normal rat spleens contain suppressor cells which can inhibit proliferative and cytotoxic responses of lymphocytes to alloantigens in vitro. The suppressor cells are adherent, phagocytic, resistant to treatment with ATS and C, radioresistant, resistant to treatment with mitomycin C, apparently absent from the thymus, and found in very high concentrations in peritoneal exudates. These characteristics indicate that the suppressor cell is a macrophages and not a T cell. When suppressor cells were removed from spleen cell suspensions, strong in vitro proliferative and cytotoxic responses to alloantigens could consistently be observed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22959/1/0000526.pd

Immunologic monitoring and immunotherapy in Ewing's sarcoma

Serial immunological monitoring was performed on 31 patients with Ewing's sarcoma who were on a randomized immunotherapy trial with BCG administered by dermal scarification with a Heaf gun. Patients were skin-tested for delayed hypersensitivity reactions (DCHR) to recall antigens and extracts of tumor cells, and with keyhole limpet hemocyanin (KLH). In vitro testing consisted of lymphocyte counts, percentages of cells forming rosettes with sheep erythrocytes at 29° C and at 4° C, and leukocyte migration inhibition to tuberculin (PPD) and to 3 M KCl extracts of tumor cells. At the time of diagnosis, nearly all patients had positive DCHR to mumps and streptococcal antigens and were negative to PPD. Neither the skin tests nor the lymphocyte counts at this time gave useful prognostic information. In tests during and after therapy, the patients who responded and remained free of detectable disease had a higher incidence of DCHR to KLH and of rosette values in the normal range than did the patients who developed recurrent disease. The BCG immunotherapy had no apparent effect on immunologic parameters except for conversion of reactions to PPD.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46861/1/262_2004_Article_BF00200108.pd

A phase I trial of recombinant gamma interferon in patients with cancer

A total of 11 patients were treated on an escalating, single dose trial of recombinant gamma interferon (rIFN-γ), 6 patients by the i.m. and 5 patients by the i.v. route of administration. Dose ranges within each individual were from 0.05 mg/m 2 of IFN (1 mg≥10×10 6 units of IFN) escalating to 10 mg/m 2 . All dosages were delivered twice weekly and the i.v. dose was infused over 5 min. The most common toxicities encountered included fever, chils, fatigue, anorexia, and granulocytopenia. The influenzalike symptoms were very similar to those encountered with IFN-α but were generally less severe. The granulocytopenia was dose-related and transient with recovery generally seen within 48–72 h following administration of rIFN-γ. Absolute granulocyte counts only rarely dropped below 1000 mm 3 . Hepatotoxicity was not observed. IFN levels were determined by both a bioassay and an enzyme-linked immunosorbent assay. By the i.v. route, the peak level of IFN activity could usually be seen at completion of the infusion with a serum half-life of 30 min. By the i.m. route, the peak level of serum activity was generally detected between 4–8 h with a serum half-life of 4.5 h after the initial elimination phase. Peak IFN levels appeared to correlate with maximum toxicity. One patient with melanoma had a 25% reduction in a cutaneous lesion, but there were no other minimal, partial, or complete responses.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46852/1/262_2004_Article_BF00205575.pd

A Novel Cross-Disciplinary Multi-Institute Approach to Translational Cancer Research: Lessons Learned from Pennsylvania Cancer Alliance Bioinformatics Consortium (PCABC)

Background: The Pennsylvania Cancer Alliance Bioinformatics Consortium (PCABC, http://www.pcabc.upmc.edu) is one of the first major project-based initiatives stemming from the Pennsylvania Cancer Alliance that was funded for four years by the Department of Health of the Commonwealth of Pennsylvania. The objective of this was to initiate a prototype biorepository and bioinformatics infrastructure with a robust data warehouse by developing a statewide data model (1) for bioinformatics and a repository of serum and tissue samples; (2) a data model for biomarker data storage; and (3) a public access website for disseminating research results and bioinformatics tools. The members of the Consortium cooperate closely, exploring the opportunity for sharing clinical, genomic and other bioinformatics data on patient samples in oncology, for the purpose of developing collaborative research programs across cancer research institutions in Pennsylvania. The Consortium’s intention was to establish a virtual repository of many clinical specimens residing in various centers across the state, in order to make them available for research. One of our primary goals was to facilitate the identification of cancer specific biomarkers and encourage collaborative research efforts among the participating centers.Methods: The PCABC has developed unique partnerships so that every region of the state can effectively contribute and participate. It includes over 80 individuals from 14 organizations, and plans to expand to partners outside the State. This has created a network of researchers, clinicians, bioinformaticians, cancer registrars, program directors, and executives from academic and community health systems, as well as external corporate partners - all working together to accomplish a common mission. The various sub-committees have developed a common IRB protocol template, common data elements for standardizing data collections for three organ sites, intellectual property/tech transfer agreements, and material transfer agreements that have been approved by each of the member institutions. This was the foundational work that has led to the development of a centralized data warehouse that has met each of the institutions’ IRB/HIPAA standards.Results: Currently, this “virtual biorepository” has over 58,000 annotated samples from 11,467 cancer patients available for research purposes. The clinical annotation of tissue samples is either done manually over the internet or semiautomated batch modes through mapping of local data elements with PCABC common data elements. The database currently holds information on 7188 cases (associated with 9278 specimens and 46,666 annotated blocks and blood samples) of prostate cancer, 2736 cases (associated with 3796 specimens and 9336 annotated blocks and blood samples) of breast cancer and 1543 cases (including 1334 specimens and 2671 annotated blocks and blood samples) of melanoma. These numbers continue to grow, and plans to integrate new tumor sites are in progress. Furthermore, the group has also developed a central web-based tool that allows investigators to share their translational (genomics/proteomics) experiment data on research evaluating potential biomarkers via a central location on the Consortium’s web site.Conclusions: The technological achievements and the statewide informatics infrastructure that have been established by the Consortium will enable robust and efficient studies of biomarkers and their relevance to the clinical course of cancer. Studies resulting from the creation of the Consortium may allow for better classification of cancer types, more accurate assessment of disease prognosis, a better ability to identify the most appropriate individuals for clinical trial participation, and better surrogate markers of disease progression and/or response to therapy

Suicide attempts in U.S. Army combat arms, special forces and combat medics

Abstract Background The U.S. Army suicide attempt rate increased sharply during the wars in Iraq and Afghanistan. Risk may vary according to occupation, which significantly influences the stressors that soldiers experience. Methods Using administrative data from the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS), we identified person-month records for all active duty Regular Army enlisted soldiers who had a medically documented suicide attempt from 2004 through 2009 (n = 9650) and an equal-probability sample of control person-months (n = 153,528). Logistic regression analyses examined the association of combat occupation (combat arms [CA], special forces [SF], combat medic [CM]) with suicide attempt, adjusting for socio-demographics, service-related characteristics, and prior mental health diagnosis. Results In adjusted models, the odds of attempting suicide were higher in CA (OR = 1.2 [95% CI: 1.1–1.2]) and CM (OR = 1.4 [95% CI: 1.3–1.5]), but lower in SF (OR = 0.3 [95% CI: 0.2–0.5]) compared to all other occupations. CA and CM had higher odds of suicide attempt than other occupations if never deployed (ORs = 1.1–1.5) or previously deployed (ORs = 1.2–1.3), but not when currently deployed. Occupation was associated with suicide attempt in the first ten years of service, but not beyond. In the first year of service, primarily a time of training, CM had higher odds of suicide attempt than both CA (OR = 1.4 [95% CI: 1.2–1.6]) and other occupations (OR = 1.5 [95% CI: 1.3–1.7]). Discrete-time hazard functions revealed that these occupations had distinct patterns of monthly risk during the first year of service. Conclusions Military occupation can inform the understanding suicide attempt risk among soldiers.https://deepblue.lib.umich.edu/bitstream/2027.42/136790/1/12888_2017_Article_1350.pd