Induction of immunoglobulin secretion in follicular non-Hodgkin's lymphomas: role of immunoregulatory T cells

B cell neoplasms are clonal expansions of B lymphocytes thought to be frozen at various points along the normal B cell differentiation pathway. We studied cell suspensions from lymph nodes involved by follicular (nodular) non-Hodgkin's lymphoma to determine the capacity of the malignant B cells to secrete immunoglobulin (Ig). Neoplastic B cells from all 14 follicular lymphomas secreted monoclonal immunoglobulin in culture when appropriate signals were provided. In most cases, maximal Ig secretion occurred when autologous T cells were removed by E rosette depletion, replaced with allogeneic normal T cells, and the cultures were exposed to 12-O-tetradecanoylphorbol-13- acetate. Autologous T cells exerted a suppressor effect on Ig secretion in 8/8 cases studied, diminishing the response of the malignant B cells to allogeneic T cells. This suppressor effect did not correlate with the percentage of cells staining with anti-Leu-2a or with "helper- suppressor" (Leu-3a-Leu-2a) ratios of the lymph node T cells. Our findings demonstrate that the arrested differentiation of most follicular lymphomas is reversible and implicate a T cell-mediated host immunoregulatory mechanism affecting Ig secretion in vivo. An additional contribution of our results is the demonstration of a cell culture system for synthesis of sufficient monoclonal Ig for use as an immunogen in production of anti-idiotype antibodies.     

A double-blind provocative study chocolate as a trigger of headache

A provocative double blind study of headache was performed using chocolate as the active agent and carob as the placebo. The chocolate and carob samples were formulated to duplicate products used in an earlier study (1) in which strong differential effects between the ability of chocolate and carob to trigger headache in migraine were shown. Sixty-three women with chronic headache (50% migraine, 37.5% tension-type, 12.5% combined migraine and tension-type) participated in the study. After 2 weeks of following a diet that restricted vasoactive amine-rich foods, each subject underwent double-blinded provocative trials with two samples of chocolate and two of carob presented in random order. Diaries were maintained by the subjects throughout the study, monitoring diet and headache. The results demonstrated that chocolate was not more likely to provoke headache than was carol in any of the headache diagnostic groups (²(2) 0.36, p =0.83). Interestingly, these results were independent of subjects' beliefs regarding the role of chocolate in the instigation of headache (²(1)=0.73, p =0.39). Headache diagnosis and the concomitant use of additional vasoactive amine-containing foods were also not associated with chocolate acting as a headache trigger. Thus, contrary to the commonly held belief of patients and physicians, chocolate does not appear to play a significant role in triggering headaches in typical migraine, tension-type, or combined headache sufferers.     

Hantavirus reservoir Oligoryzomys longicaudatus spatial distribution sensitivity to climate change scenarios in Argentine Patagonia

Background  

Oligoryzomys longicaudatus (colilargo) is the rodent responsible for hantavirus pulmonary syndrome (HPS) in Argentine Patagonia. In past decades (1967–1998), trends of precipitation reduction and surface air temperature increase have been observed in western Patagonia. We explore how the potential distribution of the hantavirus reservoir would change under different climate change scenarios based on the observed trends.     

Species-dependent variations in erythrocyte membrane skeletal proteins

Two mammalian species (porcine and murine) have erythrocytes that are being widely used to study membrane protein synthesis and red cell aging. Erythrocytes of these species however, are significantly smaller than those of the human. Before results obtained from study of these red cells can be applied to human cells, the membrane skeleton of these species must be investigated to determine if the skeletal elements are equivalent. Both pig and mouse bands 4.1b were of lower molecular weight than human 4.1b, and the a/b ratio was lower. In each species, 4.1a and b were sequence-related phosphoproteins, and yielded substantially different one-dimensional peptide maps. Band 3 of pig and mouse erythrocytes had a higher molecular weight than human band 3 and also had differing one-dimensional peptide maps after limited proteolytic cleavage with three different enzymes. In each species, free band 3 and band 3 bound to the membrane skeleton had identical peptide maps. Other major membrane skeletal components (spectrin, actin, and bands 2.1 and 4.2) seem to be very similar in molecular weight in various species. These results demonstrate that the molecular weights and relative proportions of the membrane skeletal elements are species dependent.     

Thrombosis in inflammatory bowel disease: clinical setting, procoagulant profile and factor V Leiden

Patients with inflammatory bowel disease have an increased frequency of thromboembolism, and microvascular thrombosis has been proposed as a contributory pathogenic factor. The mechanism of enhanced procoagulant activity is not understood. We examined the clinical setting of thromboembolic events in 52 patients with Crohn's disease or ulcerative colitis, and assessed the procoagulant laboratory profile, including Factor V Leiden, in a subset of 20 patients to identify procoagulant risk factors. Patients who developed thrombosis tended to be young; 60% of thrombotic events occurred in patients under 50 years. Multiple thromboembolic episodes occurred in 13% and unusual sites of thrombosis (e.g. intracardiac, cerebral, inominate veins) in 11%. No risk factor was identifiable in 52% of cases and two-thirds of thromboses occurred in an out-patient setting. The mortality rate was 8%. Evidence for inflammatory disease activity was found in only 45% of patients with ulcerative colitis at the time of the thromboembolic event, in contrast to 89% of those with Crohn's disease. Assays for specific coagulation defects were negative in all cases tested (protein S, C were normal in 17/17; anti-thrombin III, anti-phospholipid antibodies and activated protein C resistance were negative in 20/20, and only 1/20 patients was found to be heterozygous for Factor V leiden. Thrombosis in inflammatory bowel disease is important because it occurs in a young population, often in unusual sites, and has a high mortality. The development of thrombosis is related to active inflammatory disease in most patients with Crohn's disease but apparently not in those with ulcerative colitis. Since approximately half of the patients had no other identifiable risk factor, there remains a substantial group of patients with IBD who develop thrombosis for unknown reasons.      

Migraine-associated vertigo

A retrospective analysis was performed on consecutive series of 363 patients presenting with vertigo; 32% had migraine. Of the 224 patients with no pathology other than migraine or vestibular dysfunction, migraineurs had a significantly higher prevalence of normal, central, and combined central and peripheral vestibular dysfunction compared to non-migraineurs. The combination of central and peripheral vestibular signs was a feature of migraine with aura. The results support the hypothesis that migraine-associated vertigo is a diagnostic entity.     

A highly sensitive and specific chemiluminescent enzyme-linked immunosorbent assay for diagnosis of active Trypanosoma cruzi infection

BACKGROUND: Chagas' disease is transmitted to man either by the bite of insects harboring Trypanosoma cruzi or by the transfusion of blood from infected donors. The conventional serologic testing as presently used in blood banks in South America is unsatisfactory, because of a high number of inconclusive and false-positive results. Other methods such as polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA) with recombinant antigens have been proposed, but inherent difficulties have so far precluded their adoption in the large-scale screening required by blood banks. STUDY DESIGN AND METHODS: A highly sensitive and specific chemiluminescent ELISA using a purified trypomastigote glycoconjugate antigen and a complex epimastigote antigen was devised for the diagnosis of active T. cruzi infection. RESULTS: Chemiluminescent ELISA was 100-percent sensitive in the diagnosis of 100 cases of confirmed Chagas' disease. Inconclusive results and false-positive reactions were eliminated in a panel of 115 sera.The specificity of the chemiluminescent ELISA was 100 percent with a purified trypomastigote glycoconjugate antigen and 99.7 percent with a complex epimastigote antigen when applied to 1000 normal human sera and 288 heterologous sera from patients with other infections, including leishmaniasis, and vaccinated individuals. CONCLUSION: The chemiluminescent ELISAs provide a test that is highly sensitive (purified trypomastigote glycoconjugate and complex epimastigote antigens) and specific (purified trypomastigote glycoconjugate antigen) for Chagas' disease diagnosis. It can be used in blood bank screening and to monitor the treatment of patients undergoing chemotherapy.