Use of protein A immunoadsorption as a treatment for thrombocytopenia in HIV-infected homosexual men: a retrospective evaluation of 37 cases.

Thirty-seven HIV-infected homosexual men with thrombocytopenia (less than 100 x 10(9)/l) received protein A immunoadsorption treatments to remove platelet-sensitizing immunoglobulin (Ig) G and circulating immune complexes (CIC) from plasma. Patients received an average of six treatments each, consisting of 250 ml plasma over a 3-week period. Clinical improvement in hemorrhagic symptoms associated with substantial increase in platelet counts was achieved in 18 patients. These responses were maintained over a median follow-up period of more than 7 months in 14 evaluable patients who were not lost to follow-up (three patients relapsed in 2 weeks and one received another therapy). Generally, moderate transient treatment-related side-effects included fever, musculoskeletal pain, chills and nausea. A transient serum sickness-like reaction was observed in seven patients, leading to termination of treatment in two. Clinical responses were associated with significant decreases in levels of platelet-sensitizing Ig, including CIC. Stimulation of broadly cross-reactive anti-antigen-binding fragment [F(ab)2], antibodies contributed to these responses. Protein A immunoadsorption is an effective alternative treatment for HIV-associated thrombocytopenia.     

Actions of ethanol and acetate on rat cortical neurons: ethanol/adenosine interactions.

Recent studies have suggested that ethanol may exert some of its central depressant actions by increasing the extracellular levels of adenosine in the brain. Ethanol can inhibit the cellular uptake of adenosine, thus increasing its extracellular concentration. After ethanol metabolism by the liver, blood acetate levels are elevated and acetate metabolism in the brain could also lead to the production of adenosine. Rat cerebral cortical cup release experiments failed to reveal any elevation in the extracellular levels of either adenosine or inosine following the intraperitoneal (IP) administration of ethanol (1.5 g/kg) or acetate (2 g/kg). IP-administered ethanol (0.5 and 1.0 g/kg) enhanced the magnitude and duration of the inhibition by iontophoretically applied adenosine of the spontaneous firing of rat cerebrocortical neurons; an action which would be consistent with the block of adenosine uptake. Acetate, applied iontophoretically, depressed the spontaneous firing of 63% of the cerebrocortical neurons tested. 8-p-Sulphophenyltheophylline, an adenosine antagonist, was ineffective at blocking these inhibitions, indicating that adenosine generation is unlikely to have played a major role in the acetate-evoked depression of cerebral cortical neurons.     

MINERVA-a multi-modal radiation treatment planning system.

Researchers at the Idaho National Engineering and Environmental Laboratory and Montana State University have undertaken development of MINERVA, a patient-centric, multi-modal, radiation treatment planning system. This system can be used for planning and analyzing several radiotherapy modalities, either singly or combined, using common modality independent image and geometry construction and dose reporting and guiding. It employs an integrated, lightweight plugin architecture to accommodate multi-modal treatment planning using standard interface components. The MINERVA design also facilitates the future integration of improved planning technologies. The code is being developed with the Java Virtual Machine for interoperability. A full computation path has been established for molecular targeted radiotherapy treatment planning, with the associated transport plugin developed by researchers at the Lawrence Livermore National Laboratory. Development of the neutron transport plugin module is proceeding rapidly, with completion expected later this year. Future development efforts will include development of deformable registration methods, improved segmentation methods for patient model definition, and three-dimensional visualization of the patient images, geometry, and dose data. Transport and source plugins will be created for additional treatment modalities, including brachytherapy, external beam proton radiotherapy, and the EGSnrc/BEAMnrc codes for external beam photon and electron radiotherapy.     

Effect of smoking on fibronectin production by human amnion and placenta.

Fibronectin production from amnion and placental tissues was evaluated in pregnant woman smokers and nonsmokers in order to examine if there were alterations of fibronectin metabolism in intrauterine tissues. In both amnion and placental tissues, cycloheximide inhibited the fibronectin output indicating that it was being synthesized. Mean fibronectin output by amnion in pregnant woman smokers was significantly lower than that in pregnant woman nonsmokers. In contrast, in the placenta from pregnant woman smokers, the output was significantly higher than that in pregnant woman nonsmokers. The present observations indicate that smoking alters an important biochemical constituent in amnion and placenta, possible leading to some complications.     

Quantitative structural analysis of collagen in chordae tendineae and its relation to floppy mitral valves and proteoglycan infiltration

Imbibition analysis, a polarised light microscopy technique, was used to examine the molecular organisation of collagen in normal and diseased mitral valve chordae tendineae. A single strut chorda from each of 23 valves (14 from necropsy specimens and nine from valve replacement surgery) was studied. The degree of molecular organisation of collagen in unstained 7 micron sections of the chordae was assessed by measuring the retardation of polarised light by the sample. Sections from each tendon were examined, after staining with Movat's pentachrome, for the presence of proteoglycan infiltration and classified as normal or abnormal on that basis. The imbibition analysis results were grouped accordingly. The retardation in the collagen in the seven chordae with proteoglycan infiltration was significantly lower than in the 16 normal chordae, indicating decreased molecular organisation. Five of the seven abnormal chordae with proteoglycan infiltration and decreased retardation were from patients with floppy mitral valves; the other two were from normal necropsy specimens. Although proteoglycan infiltration may not be a specific marker for floppy valve disease, its presence is associated with decreased molecular organisation of collagen in the chordae. Degradation of the ground substance bound to the collagen is the most plausible explanation for the measured optical changes.     

Anesthetics Inhibit Acetylcholine-promoted Guanine Nucleotide Exchange of Heterotrimeric G Proteins of Airway Smooth Muscle

Background: Anesthetics inhibit airway smooth muscle contraction in part by a direct effect on the smooth muscle cell. This study tested the hypothesis that the anesthetics halothane and hexanol, which both relax airway smooth muscle in vitro, inhibit acetylcholine-promoted nucleotide exchange at the [alpha] subunit of the Gq/11 heterotrimeric G protein (G[alpha]q/11; i.e., they inhibit muscarinic receptor-G[alpha]q/11 coupling).

Methods: The effect of halothane (0.38 +/- 0.02 mm) and hexanol (10 mm) on basal and acetylcholine-stimulated G[alpha]q/11 guanosine nucleotide exchange was determined in membranes prepared from porcine tracheal smooth muscle. The nonhydrolyzable, radioactive form of guanosine-5'-triphosphate, [35S]GTP[gamma]S, was used as the reporter for G[alpha]q/11 subunit dissociation from the membrane to soluble fraction, which was immunoprecipitated with rabbit polyclonal anti-G[alpha]q/11 antiserum.

Results: Acetylcholine caused a significant time- and concentration-dependent increase in the magnitude of G[alpha]q/11 nucleotide exchange compared with basal values (i.e., without acetylcholine), reaching a maximal difference at 100 [mu]m (35.9 +/- 2.9 vs. 9.8 +/- 1.2 fmol/mg protein, respectively). Whereas neither anesthetic had an effect on basal G[alpha]q/11 nucleotide exchange, both halothane and hexanol significantly inhibited the increase in G[alpha]q/11 nucleotide exchange produced by 30 [mu]m acetylcholine (by 59% and 68%, respectively).