Endogenous growth of population and income depending on resource and knowledge.

PIP: This study focuses on the dynamic, endogenous, nonlinear interactions between the economy, population growth and the environment. Literature on endogenous growth theory was reviewed and the 3-sector demoeconomic model was provided as the analytical framework for the study of sustainable development through the integration of population growth, resource use and economic growth. The model is described in such a way that the labor force is considered as a free migrating variable among three different kinds of employment: the primary sector, which harvests a renewable resource, the secondary or industrial sector, and the tertiary sector, which is responsible for the accumulation of the stock that represents a public good for all three sectors. Presented in this paper is a nontechnical outline of the model that describes the economic, demographic, and environmental interactions considered. Also given are dynamics, market equilibrium and dynamic feedback rules. Furthermore, numerical analysis of the model quantifying the resulting time paths of the variables involved is included. The dynamics are simply the outcome of the nonlinear interactions of the demographic, economic and environmental modules. Numerical studies have also shown that the system variables move with different velocity. Technology and population can generally be regarded as slow moving variables by comparison with resources.^ieng

Lymphocyte recruitment and the kinetics of adhesion receptor expression during the pulmonary immune response to particulate antigen.

The selectins and beta2 integrins participate in the recruitment of neutrophils in acute pulmonary inflammation. However, the cell adhesion receptors that mediate lymphocyte trafficking into the lung have not been defined. This study examined the relationship between cell adhesion molecules on the pulmonary vasculature and on lymphocytes recovered from the lung during a pulmonary immune response to intratracheal (I.T.) sheep red blood cells (SRBCs) in sensitized C57BL/6J mice. Silver-enhanced immunogold staining and reverse transcriptase polymerase chain reaction of lung tissues revealed sustained induction of VCAM-1, E-selectin, and P-selectin on the pulmonary vasculature for up to 7 days after I.T.-SRBC challenge. Neither the MECA 79 nor MECA 367 antigens were induced on the pulmonary vasculature during this period. In the peripheral blood, both CD4 and CD8 T-cell subsets showed an initial increase in P-selectin ligand expression after I.T.-SRBC challenge. The number of P-selectin ligand-positive T cells in the peripheral blood fell as T cells with both P-selectin and, to a lesser extent, E-selectin ligands accumulated in the bronchoalveolar lavage fluid. We conclude that I.T.-SRBC challenge in sensitized mice elicits prolonged synthesis of P-selectin, E-selectin, and VCAM-1 by the lung vasculature as well as selectin ligand synthesis by responding T cells. Furthermore, the entry of selectin-ligand-positive T cells into the circulation and their accumulation in the bronchoalveolar lavage fluid indicates that these receptors may contribute to T cell recruitment. Finally, VCAM-1 on the vasculature may also participate; however, the vascular addressins, required for homing to peripheral and mucosal lymphoid organs, are not essential for T-cell entry into the lung following I.T.-SRBC challenge.

Lung lymphocyte elimination by apoptosis in the murine response to intratracheal particulate antigen.

Pulmonary immune responses are suited to determine mechanisms of lymphocyte elimination, as lung inflammation must be regulated tightly to preserve gas exchange. The self-terminating response of primed C57BL/6 mice to intratracheal challenge with the T cell-dependent Ag sheep erythrocytes (SRBC) was used to test the importance of lung lymphocyte apoptosis in pulmonary immunoregulation. Apoptosis of alveolar and interstitial lymphocytes was demonstrated morphologically, by three independent methods to detect DNA fragmentation, and by surface expression of phosphatidylserine. Apoptotic lymphocytes were exclusively CD4-, CD8-, B220-, but many were CD3+ and Thy 1+. Inhibiting apoptosis by in vivo cyclosporine treatment prolonged lung lymphocyte accumulation following SRBC challenge. Experiments using mice homozygous for the lpr or gld mutations showed that pulmonary lymphocyte apoptosis depended on expression of Fas (CD95) and its ligand (Fas-L). Pulmonary inflammation increased on repeated intratracheal SRBC challenge of lpr/lpr mice, in contrast to the waning response in normal mice. These results confirm that in situ lymphocyte apoptosis contributes to termination of immune responses in nonlymphoid organs, probably because of activation-induced cell death, and may be important in inducing tolerance to repeated antigen exposure.

Iodine-131-anti-B1 radioimmunotherapy for B-cell lymphoma.

PURPOSE: The CD20 B-lymphocyte surface antigen expressed by B-cell lymphomas is an attractive target for radioimmunotherapy, treatment using radiolabeled antibodies. We conducted a phase I dose-escalation trial to assess the toxicity, tumor targeting, and efficacy of nonmyeloablative doses of an anti-CD20 monoclonal antibody (anti-B1) labeled with iodine-131 (131I) in 34 patients with B-cell lymphoma who had failed chemotherapy. PATIENTS AND METHODS: Patients were first given tracelabeled doses of 131I-labeled anti-B1 (15 to 20 mg, 5 mCi) to assess radiolabeled antibody biodistribution, and then a radioimmunotherapeutic dose (15 to 20 mg) labeled with a quantity of 131I that would deliver a specified centigray dose of whole-body radiation predicted by the tracer dose. Whole-body radiation doses were escalated from 25 to 85 cGy in sequential groups of patients in 10-cGy increments. To evaluate if radiolabeled antibody biodistribution could be optimized, initial patients were given one or two additional tracer doses on successive weeks, each dose preceded by an infusion of 135 mg of unlabeled anti-B1 one week and 685 mg the next. The unlabeled antibody dose resulting in the most optimal tracer biodistribution was also given before the radioimmunotherapeutic dose. Later patients were given a single tracer dose and radioimmunotherapeutic dose preceded by infusion of 685 mg of unlabeled anti-B1. RESULTS: Treatment was well tolerated. Hematologic toxicity was dose-limiting, and 75 cGy was established as the maximally tolerated whole-body radiation dose. Twenty-eight patients received radioimmunotherapeutic doses of 34 to 161 mCi, resulting in complete remission in 14 patients and a partial response in eight. All 13 patients with low-grade lymphoma responded, and 10 achieved a complete remission. Six of eight patients with transformed lymphoma responded. Thirteen of 19 patients whose disease was resistant to their last course of chemotherapy and all patients with chemotherapy-sensitive disease responded. The median duration of complete remission exceeds 16.5 months. Six patients remain in complete remission 16 to 31 months after treatment. CONCLUSION: Nonmyeloablative radioimmunotherapy with 131I-anti-B1 is associated with a high rate of durable remissions in patients with B-cell lymphoma refractory to chemotherapy.

Slow-fast dynamics in a model of population and resource growth.

"Models of the interaction of population, the economy, and the environment often contain nonlinear functional relationships and variables that move at different speeds. These properties foster apparent unpredictabilities in system behaviour. Using a simple deterministic model of demographic, economic and environmental interactions we illustrate the usefulness of geometric singular perturbation theory in environmental population economics. In contrast to local stability analysis, the theory of slow-fast dynamics helps to gain new insights into the global behaviour of the system. In particular, the knowledge of the basins of attraction of the stationary states enables one to determine the regions of sustainable future paths of resources and population." (SUMMARY IN FRE)

Radioimmunotherapy of B-cell lymphoma with [131I]anti-B1 (anti-CD20) antibody.

BACKGROUND: Many patients with non-Hodgkin's lymphomas are not cured by current therapies, and new approaches to treatment are needed. As part of an ongoing phase 1 study, we examined the effect of radioimmunotherapy with 131I-labeled B-cell-specific anti-CD20 monoclonal antibody in 10 patients with CD20-positive B-cell lymphomas in whom primary chemotherapy had failed. METHODS AND RESULTS: Anti-B1 (anti-CD20) mouse monoclonal antibody trace-labeled with 131I (15 mg containing 5 mCi) was given intravenously at approximately one-week intervals: first, without pretreatment with unlabeled anti-B1 antibody, to all 10 patients; then, with pretreatment with 135 mg of unlabeled antibody, to 8 patients; and then, with pretreatment with 685 mg, to 2 patients. Serial quantitative gamma-camera images and measures of whole-body radioactivity were obtained after each tracer dose. All known disease sites larger than 2 cm could be imaged. The effect of a pretreatment dose of unlabeled anti-B1 antibody on targeting of the tumor with the radiolabeled antibody was variable. The pretreatment dose of unlabeled antibody that produced the highest ratio of the tumor dose to the whole-body dose in tracer studies was then used to deliver higher doses of radioactivity for radioimmunotherapy in nine patients. Three patients received doses designed to deliver 25 cGy to the whole body (two patients treated twice, six to eight weeks apart), four patients received 35 cGy (one patient treated twice), and two patients received 45 cGy (one patient treated twice); each dose contained 34 to 66 mCi of activity. Six of the nine treated patients had tumor responses, including patients with bulky or chemotherapy-resistant disease: four patients had complete remissions, and two had partial responses. Three patients had objective responses to tracer infusions before they received radioimmunotherapeutic doses. Of the four patients with complete remissions, one remained in remission for eight months and the other three continue to have no disease progression (for 11, 9, and 8 months). There was mild or no myelosuppression. CONCLUSIONS: Radioimmunotherapy with [131I]anti-B1 antibody is a promising new treatment for lymphoma.