Immunization with the conjugate vaccine Vi-CRM(197) against Salmonella Typhi induces Vi-specific mucosal and systemic immune responses in mice

Typhoid fever is a public health problem, especially among young children in developing countries. To address this need, a glycoconjugate vaccine Vi-CRM(197), composed of the polysaccharide antigen Vi covalently conjugated to the non-toxic mutant of diphtheria toxin CRM(197), is under development. Here, we assessed the antibody and cellular responses, both local and systemic, following subcutaneous injection of Vi-CRM(197). The glycoconjugate elicited Vi-specific serum IgG titers significantly higher than unconjugated Vi, with prevalence of IgG1 that persisted for at least 60 days after immunization. Vi-specific IgG, but not IgA, were present in intestinal washes. Lymphocytes proliferation after restimulation with Vi-CRM(197) was observed in spleen and mesenteric lymph nodes. These data confirm the immunogenicity of Vi-CRM(197) and demonstrate that the vaccine-specific antibody and cellular immune responses are present also in the intestinal tract, thus strengthening the suitability of Vi-CRM(197) as a promising candidate vaccine against Salmonella Typhi.     

Static magnetic fields affect capillary flow of red blood cells in striated skin muscle

Blood flowing in microvessels is one possible site of action of static magnetic fields (SMFs). We evaluated SMF effects on capillary flow of red blood cells (RBCs) in unanesthetized hamsters, using a skinfold chamber technique for intravital fluorescence microscopy. By this approach, capillary RBC velocities (v(RBC)), capillary diameters (D), arteriolar diameters (D(art)), and functional vessel densities (FVD) were measured in striated skin muscle at different magnetic flux densities. Exposure above a threshold level of about 500 mT resulted in a significant (P < 0.001) reduction of v(RBC) in capillaries as compared to the baseline value. At the maximum field strength of 587 mT, v(RBC) was reduced by more than 40%. Flow reduction was reversible when the field strength was decreased below the threshold level. In contrast, mean values determined at different exposure levels for the parameters D, D(art), and FVD did not vary by more than 5%. Blood flow through capillary networks is affected by strong SMFs directed perpendicular to the vessels. Since the influence of SMFs on blood flow in microvessels directed parallel to the field as well as on collateral blood supply could not be studied, our findings should be carefully interpreted with respect to the setting of safety guidelines.     

Soluble interleukin-2 receptor in hairy-cell leukemia: a reliable marker of disease

Summary The CD25 molecule, which corresponds to the p55 α chain of the interleukin-2 receptors, is strongly expressed by neoplastic cells in hairy-cell leukemia and is released in large amounts in the soluble form which is detectable in serum. In order to assess the reliability of the soluble interleukin-2 receptor as a disease marker in the management of patients with hairy-cell leukemia, we investigated serum levels in 35 untreated patients and in 2 patients with the hairy-cell leukemia variant. In 21 of 35 patients soluble receptor levels were also monitored during and after recombinant interferon-α therapy. Clinical and hematological parameters were also assessed. Soluble interleukin-2 receptor levels were extremely high at the time of diagnosis in patients with typical hairy-cell leukemia [32,722±27,001 vs. 331±145 units/ml in controls (mean±SD)], but not in patients with the leukemia variant. A progressive decrease in soluble interleukin-2 receptor levels paralleled the clinical response to treatment, although normal values were never detected, even in patients who achieved an apparent complete remission. After recombinant interferon-α discontinuation, disease recurrence was accompanied by a progressive increase to pre-treatment soluble receptor levels. Overall, a close correlation was found between soluble interleukin-2 receptor values and total tumor burden (r=0.84,P<0.001). On the basis of these data, soluble interleukin-2 receptor should be regarded as a key marker in the management of patients with hairy-cell leukemia.     

Natural fluorescence of normal and neoplastic human colon: A comprehensive “ex vivo” study

Background and Objective : A microspectrofluorometric analysis on “ex vivo” samples from normal tissue and adenocarcinoma of the human colon has been performed to characterize the histological, biochemical, and biophysical bases of the autofluorescence. Study Design/Materials and Methods: Differences between normal and tumor tissues are found that concern both the intensity distribution and spectral shape of the autofluorescence emission. The different pattern of the fluorescence intensity can be related to the histological organization of the tissue, and involves mainly the arrangement of the submucosa, the most fluorescent layer. Results: The most evident differences in the spectral shape found in the 480–580 nm range involve the stromal compartment, seem to be due to the presence of different fluorochromes, and are possibly related to the host response to the tumor. Conclusion: The nature and the extent of the autofluorescence modification between normal and tumor tissue in sections explain at least partly the evidence of the “in vivo” analysis and highlight the importance of excitation for full exploitation of the potentials of autofluorescence in diagnosis. © 1995 Wiley-Liss, Inc.