The role of adhesion molecules in human leukocyte attachment to porcine vascular endothelium: implications for xenotransplantation

Many obstacles still prevent successful xenotransplantation of porcine donor organs. When hyperacute rejection is averted, transplanted pig organs are subject to acute vascular and cellular rejection. In autologous systems, leukocyte recruitment into inflamed tissues involves selectins, integrins, and Ig family members. To determine whether these mechanisms allow human leukocytes to effectively enter porcine grafts, the pathways by which human leukocytes adhere to TNF-alpha-stimulated porcine aortic endothelium were examined under static and physiologic flow conditions. L-selectin and E-selectin had overlapping functions in neutrophil capture and rolling, whereas Ab blockade of E-selectin and the beta2 integrins inhibited firm arrest of rolling neutrophils. Combined blockade of selectins and beta2 integrins resulted in negligible human neutrophil attachment to pig endothelium. Lymphocyte attachment to porcine endothelium was primarily L-selectin mediated, whereas beta2 integrin and VCAM-1/very late Ag-4 (VLA-4) interactions promoted static adhesion. Concurrent beta2 integrin, VLA-4, VCAM-1, and L-selectin blockade completely inhibited lymphocyte attachment. Thus, interactions between leukocyte-endothelial cell adhesion receptor pairs remained remarkably intact across the human-porcine species barrier. Moreover, disrupting the adhesion cascade may impair the ability of human leukocytes to infiltrate a transplanted porcine organ during rejection.     

Treatment and prognosis of lobar and segmental atelectasis in cystic fibrosis

Studies are presented of the effect of procaine group anesthetics on rat brain synaptosome stability to dodecyl sulfate and on catalytic properties of the membrane bound alkaline phosphatase. The dose curves of detergent stability are characterized by two maxima, one at 3.10(-4) M for tetracaine, 2.10(-6) M for lidocaine and 5.10(-5) M for procaine; the other being at 10(-3) M for all anesthetics. The curves of Vmax and KM versus procaine concentration to exhibit the minimum at 5.10(-7) M and maximum at 3,2.10(-6) M. Procaine at 5.10(-7) M increases enthalpy and enthropy of membraneous alkaline phosphatase. It is suggested that interactions between anesthetics and centers of high affinity lead to synaptosome structural rearrangements, which affect the properties of membraneous enzymes.     

Evidence for active and passive urate transport in the rat proximal tubule

Studies utilizing the technique of simultaneous microperfusion of peritubular capillaries and tubular lumen of the proximal tubule of the rat were performed to determine if the absorption of urate was an active transport process and to determine the passive permeability coefficient for urate. When radioactive urate of equal specific activity and concentration was present in both perfusion solutions, the ratio of collected to initial concentrations of urate in the luminal perfusate (CO/CI) was 0.71 +/- 0.02. This gradient was higher than that predicted at equilibrium from the electrical potential difference determined in the in vitro perfused rabbit proximal tubule. The addition of para-chloromercuribenzoate (PCMB) to both solutions resulted in a significantly higher CO/CI of 0.90 +/- 0.02. This latter value is closer to the value predicted at electrochemical equilibrium. In separate studies, the unidirectional fluxes of urate were determined in the presence of PCMB. The calculated passive permeability coefficient averaged approximately 0.94 pmol . min-1 . mm-1 . mM-1 and was equal in both directions. These results indicate that in the rat proximal tubule urate absorption is an active transport process. In addition, there exists a passive permeation pathway for urate movement out of and into the proximal tubule.     

Immunological and functional characterization of Mycobacterium leprae protein antigens: an overview

A major focus of leprosy research in the last 10 years has been the identification and characterization of antigens of Mycobacterium leprae that interact with antibodies and T cells of the host's immune response. Through the combined efforts of many different laboratories, a substantial number of protein antigens have been identified and characterized. In this MicroReview we present an updated list of M. leprae protein antigens, and, with emphasis on recent developments, summarize what is known regarding their functional and immunological features.     

Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group

BACKGROUND: Previous studies have shown that alendronate can increase bone mineral density (BMD) and prevent radiographically defined (morphometric) vertebral fractures. The Fracture Intervention Trial aimed to investigate the effect of alendronate on the risk of morphometric as well as clinically evident fractures in postmenopausal women with low bone mass. METHODS: Women aged 55-81 with low femoral-neck BMD were enrolled in two study groups based on presence or absence of an existing vertebral fracture. Results for women with at least one vertebral fracture at baseline are reported here. 2027 women were randomly assigned placebo (1005) or alendronate (1022) and followed up for 36 months. The dose of alendronate (initially 5 mg daily) was increased (to 10 mg daily) at 24 months, with maintenance of the double blind. Lateral spine radiography was done at baseline and at 24 and 36 months. New vertebral fractures, the primary endpoint, were defined by morphometry as a decrease of 20% (and at least 4 mm) in at least one vertebral height between the baseline and latest follow-up radiograph. Non-spine clinical fractures were confirmed by radiographic reports. New symptomatic vertebral fractures were based on self-report and confirmed by radiography. FINDINGS: Follow-up radiographs were obtained for 1946 women (98% of surviving participants). 78 (8.0%) of women in the alendronate group had one or more new morphometric vertebral fractures compared with 145 (15.0%) in the placebo group (relative risk 0.53 [95% Cl 0.41-0.68]). For clinically apparent vertebral fractures, the corresponding numbers were 23 (2.3%) alendronate and 50 (5.0%) placebo (relative hazard 0.45 [0.27-0.72]). The risk of any clinical fracture, the main secondary endpoint, was lower in the alendronate than in the placebo group (139 [13.6%] vs 183 [18.2%]; relative hazard 0.72 [0.58-0.90]). The relative hazards for hip fracture and wrist fracture for alendronate versus placebo were 0.49 (0.23-0.99) and 0.52 (0.31-0.87). There was no significant difference between the groups in numbers of adverse experiences, including upper-gastrointestinal disorders. INTERPRETATION: We conclude that among women with low bone mass and existing vertebral fractures, alendronate is well tolerated and substantially reduces the frequency of morphometric and clinical vertebral fractures, as well as other clinical fractures.     

Health care workers with HIV and a patient's right to know

Accidental human immunodeficiency virus (HIV) infection of patients in health care settings raises the question about whether patients have a right to expect disclosure of HIV/AIDS diagnoses by their health workers. Although such a right-and the correlative duty to disclose-might appear justified by reason of standards of informed consent, I argue that such standards should only apply to questions of risks of and barriers to HIV infection involved in a particular medical treatment, not to disclosure of personal diagnoses. Because the degree of risk of HIV infection is low and disclosure would also have damaging consequences for health workers, and because patient protection is available in other ways, it is argued that no such generalized right should be recognized.     

Multiple domain protein diagnostic patterns

We have implemented an iterative algorithm for the identification of diagnostic patterns from sets of multiple-domain proteins, where domains need not be common to all the proteins in the defining set. Our algorithm was applied to sequences gathered using a variety of methods, including BLAST, common keywords, and common E.C. numbers. In all cases, useful diagnostic patterns were obtained, possessing both high sensitivity and specificity. The patterns were found to correlate in several cases with both functional and structural domains. Patterns generated from a large number of sequence families were analyzed for probable multiple-domain structure.