Therapeutic studies in NZB/W mice. I. Synergy of azathioprine,cyclophosphamide and methylprednisolone in combination

This study compares different immunosuppressive regimens in the treatment of the lupus-like nephritis of NZB/W mice. Groups of 5-month-old female NZB/W mice were given azathioprine, cyclophosphamide and methylprednisolone in all one-, two- and three-drug regimens, each drug in the relatively low dose of 1.5 mg/kg/day. Treatment for 3 months with one or two drugs resulted in modest suppression of NZB/W disease. Mice receiving all three drugs had significantly less proteinuria, lower titers of anti-DNA antibody and less severe, histologically evident renal involvement than mice treated with one or two drugs. Survival at 1 year was 10% for untreated controls, 44% for one-drug-treated, 37% for two-drug-treated and 86% for the three-drug-treated mice. The survival for the three-drug regimen was significantly longer than any other group (P < 0.01). The three-drug regimen was synergistic, since mice treated with each drug at three times the dose had significantly more proteinuria after 3 months of treatment and lowered 1 year survival (33%). The beneficial effects of triple-drug therapy were attained without increased toxicity. This study represents the first controlled evaluation of single versus combination therapy in a model of autoimmune disease. Based on these results, a controlled evaluation of triple-drug therapy in human systemic lupus erythematosus appears warranted.     

Retinal Laser Damage Thresholds as a Function of Image Diameter

The eyes of rhesus monkeys were exposed to argon (514.5 nm) and ruby (694.3 nm) laser irradiation using various retinal image diameters which were estimated by microphotometric techniques. The experimental design for both wavelengths produced image diameters of 40μ to 50μ for the “minimal” case and approximately 500μ to 1,000μ for the larger irradiance series employed. Extramacular retinal exposure sites were examined by ophthalmoscopic and histopathological techniques. Flat preparations of the pigmented epithelium and sensory layers of the retina were utilized in the confirmation of damage at low power levels. All data were statistically analyzed to establish trends, and results were compared for the wavelengths employed. Results indicate that retinal damage is primarily dependent on energy distribution as a function of image diameter and exposure duration.     

A Roadmap for Adapting an Evidence-Based HIV Prevention Intervention: Personal Cognitive Counseling (PCC) for Episodic Substance-Using Men Who Have Sex with Men

Episodic (less than weekly) drug use and binge drinking increase HIV-related sexual risk behaviors among men who have sex with men (MSM), yet no evidence-based interventions exist for these men. We describe an adaptation process of the Personalized Cognitive Counseling (PCC) intervention for utilization with high-risk, HIV-negative episodic, substance-using MSM. Participants (N?=?59) were racially diverse, and reported unprotected anal intercourse and concurrent binge drinking (85 %), use of poppers (36 %), methamphetamine (20 %) and cocaine (12 %). Semi-structured interviews with 20 episodic, substance-using MSM elicited sexual narratives for engaging in unprotected anal intercourse while using alcohol or drugs. Emergent qualitative themes were translated into self-justifications and included in a revised PCC self-justification elicitation instrument (SJEI). The adapted SJEI was pretested with 19 episodic, substance-using MSM, and the final adapted PCC was pilot-tested for acceptability and feasibility with 20 episodic, substance-using MSM. This process can be used as a roadmap for adapting PCC for other high-risk populations of MSM.     

Glycoprotein Ib and glycoprotein IX are fully complexed in the intact platelet membrane

Two new murine monoclonal antibodies, AK 1 and SZ 1, reactive with the human platelet glycoprotein (GP) Ib-IX complex have been produced by the hybridoma technique. Both AK 1 and SZ 1 immunoprecipitated the GP Ib-IX complex from Triton X-100-solubilized, periodate-labeled platelets. With trypsinized, labeled platelets, AK 1, SZ 1, and FMC 25 (epitope on GP IX) immunoprecipitated a membrane-bound proteolytic fragment of the GP Ib-IX complex consisting of GP IX and an congruent to 25,000 mol wt remnant of the alpha-chain of GP lb disulfide-linked to the beta-subunit. Unexpectedly, although AK 1 and SZ 1 immunoprecipitated purified GP Ib-IX complex, neither antibody immunoprecipitated the individual components of this complex, GP Ib or GP IX. When GP Ib and GP IX were recombined, however, AK 1 and SZ 1 again immunoprecipitated the reformed complex, strongly suggesting that both antibodies were recognizing an epitope present only on the intact complex. Cross-blocking studies indicated that AK 1 and SZ 1 recognized a very similar or identical epitope that was proximal to the epitope for FMC 25. Both AK 1 and SZ 1 bound to a similar number of binding sites (congruent to 25,000) on intact platelets as monoclonal antibodies directed against either GP lb or GP IX. The combined data suggests that GP lb and GP IX are fully complexed in the intact platelet membrane.     

Myeloproliferative syndrome induced by MPSV in DBA/2 mice: presence of a mixed-colonies promoting activity (MPA) in the spleen

The myeloproliferative syndrome induced by the myeloproliferative sarcoma virus (MPSV) in DBA/2 mice stimulates the proliferation of pluripotent hemopoietic stem cells (HSC) and of progenitors committed toward granulomacrophagic and erythroid cell lines. This stimulation may result from a direct effect of the MPSV on HSC or from an indirect effect via locally secreted factors. Normal isogenic bone marrow cells were incubated in the mixed colony-forming unit system in semisolid medium supplemented with conditioned media obtained after incubating neoplastic spleen cells for 3 days at 37 degrees C. These spleen conditioned media contain an activity that is physically separable from MPSV by ultracentrifugation and which, in the presence of a very low quantity of erythropoietin, can induce in vitro the proliferation and differentiation of pluripotent HSC, detected by this Mix-CFU technique. We termed this activity mixed-colonies promoting activity (MPA). These results suggest that the hyperplasia of the nonlymphoid hematopoietic system in the neoplastic spleen results from an indirect effect of the MPSV on pluripotent HSC via locally secreted factors.