Transfusion-induced immunomodulation and its possible role in cancer recurrence and perioperative bacterial infection

Over the last decade, it has become evident that homologous transfusions carry immunologic consequences beyond the well-understood ones of alloimmunization to blood cell antigens. Transfusions constitute temporary transplants of large amounts of allogeneic antigen given intravenously and cause down-regulation of many cellular immune functions. These changes may explain in part the association of transfusion with such clinically important events as (1) improved survival of renal allografts, (2) decreased recurrence rates for autoimmune disease, (3) increased frequency and earlier recurrences of solid tumors, (4) increased frequency of post-operative bacterial infection, and (5) increased severity of viral infection. Preliminary data suggest that, in animal models and clinical settings, syngeneic or autologous transfusions are not associated with such events. This finding supports the hypothesis that these associations are cause and effect and involve immunologic mechanisms.     

Chemical dependency and drug testing in the workplace.

Urine testing for drug use in the workplace is now widespread, with the prevalence of positive drug tests in the work force being 0% to 15%. The prevalence of marijuana use is highest, and this can be reliably tested. Though it is prudent to rid the workplace of drug use, there is little scientific study on the relationship of drug use and workplace outcomes, such as productivity and safety. Probable-cause testing and preemployment testing are the most common applications. Random testing has been less accepted owing to its higher costs, unresolved legal issues, and predictably poor test reliability. Legal issues have focused on the right to policy, discrimination, and the lack of due process. The legal cornerstone of a good program is a policy that is planned and agreed on by both labor and management, which serves both as a contract and as a procedure in which expectations and consequences are known. The National Institute on Drug Abuse is certifying laboratories doing employee drug testing. Testing methods when done correctly are less prone to error than in the past, but screening tests can be defeated by adulterants. Although the incidence of false-positive results is low, such tests are less reliable when the prevalence of drug abuse is also low.     

Characterisation of Pseudomonas rhamnolipids

The Gram negative organism, Pseudomonas aeruginosa, is often found in the lungs of patients with cystic fibrosis and other forms of severe bronchiectasis, where it secretes a number of extracellular toxins including the mono- and dirhamnolipids. The principal monorhamnolipid from P. aeruginosa has previously been identified as rhamnosyl-3-hydroxydecanoyl-3-hydroxydecanoate (Rh-C10.C10). A number of related mono- and dirhamnolipids have been purified from cultures of a clinical isolate of P. aeruginosa and identified by fast atom bombardment and electron impact mass spectrometry: these contain the 3-hydroxyoctanoyl-3-hydroxydecanoate (C8.C10) and 3-hydroxydecanoyl-3-hydroxydodecanoate (C10.C12) homologues. Structural isomers were also present where the order of the lipid linkage was transposed (Rh-C10.C8 and Rh-C12.C10). Unsaturated mono- and dirhamnolipids containing the 3-hydroxydecanoyl-3-hydroxydodec-5-enoate (C10.C12:1) lipid were also present.     

Stimulation of CTP: phosphocholine cytidylyltransferase and phosphatidylcholine synthesis by incubation of rat hepatocytes with phospholipase A2

The effect of phospholipase A2 treatment of rat hepatocytes on CTP: phosphocholine cytidylyltransferase and phosphatidylcholine synthesis was investigated. Cytidylyltransferase is recovered from the cytosol and in a membrane-bound form with the microsomes. Digitonin treatment of cells causes rapid release into the medium of the cytosolic, but not the microsomal form of the cytidylyltransferase. Incubation of hepatocytes for 10 min with phospholipase A2 (0.9 units/dish) in the medium, resulted in a 33% decrease in the cytidylyltransferase activity released by digitonin treatment (2.5 +/- 0.15 nmol/min per mg compared to 3.9 +/- 0.10 nmol/min per mg in the control). In agreement with the digitonin experiments, incubation with 0.9 units/dish of phospholipase A2 resulted in a decrease in the cytidylyltransferase activity in the cytosol (from 4.3 +/- 0.10 nmol/min per mg to 2.6 +/- 0.14 nmol/min per mg) and a corresponding increase in the microsomal fraction (from 0.9 +/- 0.16 nmol/min per mg to 1.8 +/- 0.20 nmol/min per mg). The effect of phospholipase A2 on cytidylyltransferase translocation was concentration- and time-dependent. Incubation of hepatocytes in the presence of phospholipase A2 (0.9 units/dish) for 10 min prior to pulse-chase experiments resulted in an increase in radiolabel incorporation into phosphatidylcholine (from 2.4 +/- 0.02.10(-5) dpm/dish to 3.1 +/- 0.1.10(-5) dpm/dish) and a corresponding decrease in radiolabel associated with the choline (from 2.5 +/- 0.05.10(-5) to 1.4 +/- 0.03.10(-5) dpm) and phosphocholine fractions (from 8.5 +/- 0.07.10(-5) to 6.9 +/- 0.05.10(-5) dpm). We conclude that phospholipase A2 can cause a stimulation of CTP: phosphocholine cytidylyltransferase activity and phosphatidylcholine synthesis in cultured rat hepatocytes.     

Effects of spaceflight on the proliferation of jejunal mucosal cells

The mitotic indices, villus heights, and crypt depths were determined in each of three jejunal regions (proximal, middle, and distal) for five animals each in the flight, vivarium, and synchronous groups. Because of the rapid turnover of intestinal mucosal cells and the delay in recovering the flight animals, it is not known whether the proliferation of jejunal mucosal cells is affected by microgravity conditions associated with spaceflight. However, since there were no consistent differences between animals in the flight group and those in the synchronous and vivarium control groups, it appears that any effects of microgravity on the turnover of jejunal mucosal cells are short-lived. Thus, this study represents an initial step in determining the effects of microgravity on the proliferation and turnover of intestinal mucosal cells.     

Cross-linkage sites in type I collagen fibrils studied by neutron diffraction

Cross-links in tendon collagen are essential for the biomechanical strength of healthy tissue. The nature and position of these cross-links has long been a subject for conjecture. We have approached this problem in a non-destructive manner, by studying neutron diffraction from collagen fibrils that have been specifically deuterated by reduction at keto-amine and Schiff base groups with sodium borodeuteride (NaB2H4). The intensities of the first 23 meridional reflections were recorded for both native and reduced tendons. These data were used to calculate the neutron-scattering density profile of the 67 nm (D) repeat of type I collagen fibrils in rat tail tendon. This approach not only succeeds in determining the location of the cross-linkage sites with respect to the fibril structure, as projected onto the fibre axis, but also presents a novel form of the isomorphous derivative solution to the phase problem.     

Fusaric acid and other metabolite production in Fusarium oxysporum f. sp. vasinfectum

A thin layer chromatography system is described for the analysis of fusaric acid and other secondary metabolites, to assist in the identification of pathogenic races of Fusarium oxysporum f. sp. vasinfectum . There were differences in the metabolite profiles of the races grown on different media.