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.     

Lung lymphocytes in bleomycin-induced pulmonary disease

Previous studies have not clearly defined the role of cell-mediated immunity in bleomycin-induced lung injury. In this report the functional activity of T lymphocytes obtained from minced lung preparations, bronchoalveolar lavage, and blood of rabbits treated with bleomycin was examined in cell proliferation and cell-mediated cytotoxicity assays. Four days after instillation of bleomycin (10 units/kg) into the right lung, histologic examination revealed mononuclear cell interstitial infiltrates and alveolar exudates. Right lung bronchoalveolar lavage (BAL) cell counts were similar in both groups, but the percentage of lymphocytes and neutrophils was elevated in bleomycin-treated groups (25% vs. 7% and 35% vs. 0% respectively;p<0.05). Spontaneous proliferation of cultured BAL and blood lymphocytes was similar in bleomycin-treated rabbits and controls. After 24 h of incubation with interleukin-2 (IL-2), BAL lymphocytes from bleomycin-treated rabbits had nearly a 4-fold greater proliferative response than lymphocytes from untreated rabbits. Concanavalin-A-dependent cell-mediated cytotoxicity (CDCMC) assays were performed to evaluate cytolytic lymphocyte activity. Spontaneous CDCMC activity was not detected in BAL fluid or in blood lymphocytes from either treated or control animals. After 24 h of incubation with IL-2, significant CDCMC activity was detected in lung lymphocytes from bleomycin-treated animals, but not in lung lymphocytes from control animals. These results indicate that stimulated lymphocytes are present in the lungs of rabbits 4 days after exposure to bleomycin. Presented in part at the American Thoracic Society Annual Meeting, New Orleans, LA, May 1987.     

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.     

CD4 coating, but not CD4 depletion, is a predictor of efficacy with primatized monoclonal anti-CD4 treatment of active rheumatoid arthritis

OBJECTIVE: Double blind studies were conducted with the anti-CD4 monoclonal antibody (Mab) keliximab in patients with active, stable rheumatoid arthritis (RA), to confirm preliminary evidence of efficacy and safety from open. uncontrolled studies. METHODS: We enrolled 136 and 186 patients into 2 consecutive, randomized, double blind trials, with similar populations [apart from inclusion of disease modifying antirheumatic drug (DMARD)-na?ve patients in Study 2]. Patients received 4 weeks intravenous placebo or keliximab [40, 80, 120, or 140 mg twice weekly (bw), or 240 mg once weekly (ow)].The primary endpoint was the American College of Rheumatology (ACR) 20 response criteria, one week after the end of treatment. RESULTS: ACR 20 response rates in Study I were 19%, 42%, 51%*, and 69%* (*p < 0.05 compared to placebo), with placebo, 40, 80, or 140 mg keliximab bw, respectively. The response rates in Study 2 were 30%, 39%, 46% and 47% with placebo, 80 or 120 mg bw, or 240 mg keliximab ow, respectively. In the 2 studies, there was a dose dependent increase in peripheral blood CD4+ T cell coating with keliximab, but a different pattern of CD4 depletion was seen. While only 12% of keliximab treated patients in Study I had CD4 counts below 250 cells/mm3 at the end of the treatment period, 47% fell below this level in Study 2. Clinical response was not correlated with CD4 depletion, but was correlated with CD4+ T cell coating with keliximab. CONCLUSION: Coating of peripheral blood CD4+ T cells with keliximab, but not CD4 depletion, is a determinant of clinical response.     

Sleep-disordered breathing in alcoholics

Sleep apnea and related disorders contribute to disturbed sleep in abstinent alcoholics. In an earlier report from our group, sleep-disordered breathing was common and increased with age in a cohort of 75 abstinent alcoholics. We now report an extension of the previous work that includes studies of an additional 103 abstinent alcoholics undergoing treatment for alcoholism (total sample = 188) and a comparison group of 87 normal subjects. The presence and severity of sleep-disordered breathing was assessed with polysomnography. Among the alcoholics, sleep-disordered breathing (defined as 10 or more apneas plus hypopneas per hour of sleep) was present in 3% of 91 subjects under age 40, 17% of 83 subjects age 40 to 59, and 50% of 14 subjects age 60 or over. Subjects with sleep-disordered breathing were more likely to be male and had more severe sleep disruption and nocturnal hypoxemia and more complaints related to daytime sleepiness than subjects without sleep-disordered breathing. In a multiple linear regression analysis, age and body mass index were significant predictors of the presence of sleep-disordered breathing, whereas smoking history and duration of heavy drinking were not predictors after controlling for the effects of age and body mass index. Our findings suggest that sleep-disordered breathing contributes significantly to sleep disturbance in a substantial proportion of older alcoholics and that symptomatic sleep-disordered breathing increases with age in alcoholics. Sleep-disordered breathing, when combined with existing cardiovascular risk factors, may contribute to adverse health consequences in alcoholics.