Examining a paradox in the pathogenesis of human pulmonary tuberculosis: immune activation and suppression/anergy

Protective immunity against Mycobacterium tuberculosis (MTB) in animal models is based on cell-mediated immunity (CMI), involving bi-directional interactions between T cells and cells of the monocyte/macrophage (MO/MA) lineage. Key factors include MO-derived interleukin (IL)-12 and tumor necrosis factor (TNF)-alpha as well as T cell derived IL-2 and interferon (IFN)-gamma. These cytokines appear particularly crucial in the induction of MA-mediated elimination of mycobacteria. Several lines of evidence indicate that similar mechanisms are operating in humans. During active pulmonary tuberculosis (PTB), signs of both immune depression and immune activation are concomitantly present. Decreased tuberculin skin test reactivity in vivo and deficient IFN-gamma production by MTB-stimulated mononuclear cells in vitro are observed. On the other hand, the serum levels of several cytokines, including TNF, and other inflammatory mediators are increased and circulating MO and T cell show phenotypic and functional evidence of in vivo activation. In this review, we will discuss the evidence for three models, which could explain this apparent paradox: 1. Stimulation of the T cell-suppressive function from MO/MA; 2. Intrinsic T cell refractoriness, possibly associated with tendency to apoptosis (programmed cell death), and 3. Compartmentalization and redistribution of immune responses to the site of disease. The opportunistic behavior of MTB during human immunodeficiency virus (HIV) infection can be explained by suppression of type-1 responses at the level of antigen-presenting cells, CD4 T cells and effector macrophages. The ominous prognostic significance of intercurrent PTB during HIV infection seems primarily due to prolonged activation of HIV replication in macrophages. Supportive immune therapy during PTB could aim at correcting the type-1 deficiency either by IFN-gamma inducers (e.g. IL-12, IL-18) or by neutralizing the suppressive cytokines transforming growth factor beta (TGF-beta) and IL-10. Alternatively, inflammatory over-activity could be reduced by neutralizing TNF. Finally, anti-apoptotic therapies (e.g. IL-15) might be considered.     

Image reconstruction based on human and monkey cone mosaics

The image reconstruction capacity of the actual foveal cone sampling mosaics of an adult monkey and human is investigated through computer simulations. A retinocortical mapping model in which positions are known and disorder is compensated (DC) has been implemented using classical Whittaker-Kotelnikov-Shannon (WKS) reconstruction theory and a two-dimensional hexagonal tessellation technique that maps the cone lattice onto a perfectly hexagonal grid. The DC model has been compared with a retinocortical mapping model in which cone positions are also known but position disorder is uncompensated (DU) in the reconstruction process. A control model has also been implemented using WKS reconstruction based on sampled data obtained with simulated perfectly hexagonal lattices whose Nyquist limits are equivalent to those of the human and monkey lattices. Quantitative comparisons of these models are based on the RMS error per pixel between the original and reconstructed images. Results of these simulations demonstrate a pronounced superiority of the DC over the DU model. The results of these simulations, which use “biologically correct” sampling lattices, document a potential image reconstruction advantage when foveal cone positions are known.     

Prosthetic heart valve thrombosis: a 3-year experience

A series of 12 patients with 16 episodes of prosthetic heart-valve thrombosis over 3 years is presented. Most episodes affected mitral or tricuspid bileaflet prostheses. All patients were inadequately anticoagulated at the time of thrombosis. The clinical presentation was acute and severe in 6 patients, and subacute or chronic in the rest. Physical examination was suggestive of stuck valves in most cases. Transthoracic echocardiography revealed increased transvalvular gradients in most. However, clearer evidence of valve thrombosis was obtained from transesophageal echocardiography or fluoroscopy. 9 patients eventually had their valves re-replaced successfully, and the preoperative diagnosis was confirmed in all. 5 patients were operated as soon as the diagnosis was established. and an additional 4 were operated after failure of anticoagulation. In 4 patients the valve leaflets became completely mobile after a course of thrombolysis. Prosthetic valve thrombosis is a severe and potentially fatal complication in patients with mechanical heart valves. Alertness of physicians at all levels- the general practitioner, the internist and the cardiologist- to the possibility of valve thrombosis and to its clinical presentation may lead to prompt and earlier diagnosis and to comprehensive therapy.     

MR identification of white matter abnormalities in multiple sclerosis: a comparison between 1.5 T and 4 T

BACKGROUND AND PURPOSE: Although MR spectroscopy and functional MR imaging of the brain have been successful at 4 T, conventional fast spin-echo imaging of the brain at 4 T has not been adequately evaluated. The purpose of this study was to compare the detection of white matter abnormalities in multiple sclerosis (MS) at 1.5 T and 4 T. METHODS: Fifteen patients with clinically definite MS were imaged at both 1.5 T and 4 T within a 1-week period. Comparison was made between fast spin-echo long-TR images at both field strengths. Pulse sequences were tailored to maximize resolution and signal-to-noise ratio in clinically relevant imaging times (< 7 min). Four interpreters independently reviewed the images obtained at both field strengths in separate sessions and evaluated them for lesion identification, size, characterization, and subjective resolution. Differences in interpretations at 1.5 T and 4 T were subsequently recorded. RESULTS: Images obtained at 4 T showed a mean of 88 more lesions as compared with images obtained at 1.5 T. All the lesions measured less than 5 mm and were typically aligned along perivascular spaces. Twenty-five consensually identified lesions on 4-T images were not seen at all on 1.5-T images. Moreover, 4-T images showed 56 additional consensually identified lesions, which were indistinct and seen only in retrospect on 1.5-T images. These lesions were frequently (n = 48) identified in large confluent areas of white matter signal intensity abnormality at 1.5 T. All observers also agreed that 4-T images subjectively enhanced the perception of normal perivascular spaces and small perivascular lesions. CONCLUSION: MR imaging at 4 T can depict white matter abnormalities in MS patients not detectable at 1.5 T through higher resolution with comparable signal-to-noise ratio and imaging times.     

Potent apoptotic signaling and subsequent unresponsiveness induced by a single CD2 mAb (BTI-322) in activated human peripheral T cells

Manipulation of CD2 molecules with CD2 mAb pairs has been shown to deliver apoptotic signals to activated mature T cells. We show that BTI-322, a CD2 mAb directed at a peculiar epitope of CD2, can trigger on its own the apoptotic death of IL-2-activated peripheral T cells and of OKT3-stimulated T cells, contrasting in this respect with a series of other mouse or rat CD2 mAb. F(ab')2 fragments were as potent as the whole Ab. BTI-322-induced apoptosis proceeded in a few hours and was independent of the Fas/Fas ligand system. Less than 5 ng/ml of BTI-322, added at the beginning of culture, were able to eliminate within 4 days most CD3+ cells from OKT3- and IL-2-stimulated lymphocytes, the only cells remaining being CD16+CD2- NK cells. T cell proliferative responses induced by a mitogenic CD2 mAb pair or by PHA-P (which mainly binds to CD2) were not inhibited by BTI-322. In this case, the apoptotic effect was successfully counteracted by simultaneous enhancement of T cell divisions. Thus, the killing effect of BTI-322 was most effective when T cells were exclusively stimulated through the CD3/TCR complex. Apoptosis of the responding T cells may explain why T cells recovered from a primary MLC performed in the presence of BTI-322 responded to third party cells but not to the primary stimulatory cells. These data constitute the rational basis for the use of BTI-322 for inducing tolerance in human allotransplantation.     

Experience with the Ultrex and Ultrex Plus inflatable penile prosthesis: new implantation techniques and surgical outcome

OBJECTIVE: To construct nomograms of the size of the fetal orbit and lens during gestation. SUBJECTS: The study group included 349 normal pregnant women at 14-36 weeks' gestation. METHODS: Routine biometric measurements were obtained in all the participants; these included biparietal diameter, head and abdominal circumferences, measurements of the long bones and the diameters of the fetal orbit and lens. The orbital and lens circumference measurements were also related to gestational ages. RESULTS: A linear growth function was observed between gestational age (GA) and orbital diameter (r = 0.94; p < 0.00001; y = -0.66 + 0.5 x GA), orbital circumference (r = 0.94; p < 0.00001; y = -2.1 + 1.5 x GA) and orbital area (r = 0.94; p < 0.00001; y = -98.1 + 8.3 x GA). Significant correlation was also found between femoral length (FL) and orbital diameter (r = 0.95; p < 0.00001; y = 3.3 + 1.9 x FL), orbital circumference (r = 0.95; p < 0.00001; y = 10.3 + 5.9 x FL) and orbital area (r = 0.93; p < 0.00001; y = -28.2 + 32.2 x FL). A linear growth function was observed between orbital circumference and biparietal diameter (r = 0.94; p < 0.00001) and head circumference (r = 0.95; p < 0.00001). A linear growth function was also observed between gestational age and the diameter of the lens (r = 0.89; p < 0.00001; y = 0.88 + 1.4 x GA) the circumference of the lens (r = 0.89; p < 0.00001; y = 2.78 + 0.4 x GA) and the area of the lens (r = 0.89; p < 0.00001; y = -7.95 + 1.0 x GA). The correlation was found between the ratios of the diameters, circumferences and areas of the lens and the orbit. CONCLUSIONS: These results provide normative data of the growth of the fetal orbit and lens and may aid future studies relating to fetal eye anomalies.     

Predicted heats of combustion of some important organosilicon intermediates

This short communication presents the predicted heats of combustion of 308 organosilicon intermediates. The net and gross heats of combustion were predicted using two previously developed empirical equations. These intermediates cover most of the important organosilicon compounds that are manufactured or used in the silicone industry. Copyright © 2003 John Wiley & Sons, Ltd.     

Ontogeny of defensive reactions in Norway rats.

In 3 experiments, 219 Sprague-Dawley albino rats of several ages were presented with stimuli (a caged domestic cat, a footshock, and a suddenly moving object) known to be aversive to adults and disruptive of behavior in mature animals. 20-day-old Ss were relatively unaffected by these events, while Ss aged 30 days and older tended to reduce their locomotion and freeze upon the presentation of these cues. Data are consistent with R. C. Bolles's (1970, 1971) hypothesis that shock-elicited responses are innate defensive reactions. It is suggested that the inefficient passive avoidance learning in juvenile rats may result from their deficit in shock-induced freezing. (41 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)