The purification of red cells for transfusion by freeze-preservation and washing. IV. The use of micropore filtration to reduce the residual HL-A antigenicity of previously frozen, washed red cells

Using a semi-quantitative HL-A antibody adsorption assay, a reduction in HL-A antigenicity was observed in 15 of 22 units of previously frozen and washed red blood cells after passage through a micropore transfusion filter. Red blood cell viability was unaffected by this procedure. Micropore filtration was a simple adjunct to the freezing and washing of red blood cells that may further reduce histocompatibility antigen exposure in transfused recipients.     

DEMONSTRATION OF A BLOCKING FACTOR IN THE PLASMA AND SPINAL FLUID OF PATIENTS WITH SUBACUTE SCLEROSING PANENCEPHALITIS : I. PARTIAL CHARACTERIZATION

Conflicting reports on the immune responsiveness of patients with subacute sclerosing panencephalitis (SSPE) have been reported. This report shows that the leucocytes from four SSPE patients exhibited strong sensitivity to both measles and SSPE virus preparations as measured by the macrophage migration inhibition test, mixed lymphocyte virus infected cell culture test, and the lymphotoxin assay. Earlier suggestions that a factor may be operating to suppress cellular reactivity are confirmed by the demonstration that the response of lymphocytes from SSPE patients could be blocked by the addition of SSPE spinal fluid or plasma. It was determined that the blocking factor was stable at –20°C, heat labile at 56°C for 30 minutes, trypsin and neuraminadase sensitive, and had a mol wt greater than 150,000 as determined by Sephadex G-200 gel chromatography. The blocking factor appeared to be specific for SSPE virus and did not block the response of lymphocytes to nonspecific mitogenic agents and other viral and bacterial agents.     

STUDIES ON RABBIT LYMPHOCYTES IN VITRO : VI. THE INDUCTION OF BLAST TRANSFORMATION WITH SHEEP ANTISERA TO RABBIT IGA AND IGM

Sheep antisera specific for the three major immunoglobulin groups of the rabbit, i.e. IgG (γ-chain), IgA (α-chain), and IgM (µ-chain), are each able to induce blast transformation of the peripheral lymphocytes of the rabbit when added to in vitro cultures. The per cent of lymphocytes transformed with each antiserum indicate that one-fourth of the peripheral lymphocytes carry or have the capacity to synthesize molecules of all three of the major immunoglobulin groups, and that the remaining three-fourths carry or have the capacity to synthesize only two (IgG and IgM). The data do not permit direct conclusions concerning the ability of a single cell to produce molecules belonging to more than one immunoglobulin group at the same time, or the ability of a given cell to make a transition from the synthesis of molecules of one immunoglobulin group to those of another group.     

Higher Donor Apheresis Blood Volumes Are Associated with Reduced Relapse Risk and Improved Survival in Reduced-Intensity Allogeneic Transplantations with Unrelated Donors

Allogeneic hematopoietic stem cell transplantation (HSCT) with reduced-intensity conditioning (RIC) offers a curative option for patients with hematologic malignancies who are unable to undergo myeloablative conditioning, but its success is limited by high rates of relapse. Several studies have suggested a role for T cell doses in peripheral blood stem cell grafts in RIC HSCT. Because T cell dose is typically not known until after the collection, and apheresis blood volume is easily modifiable, we hypothesized that higher donor apheresis blood volumes would improve transplantation outcomes through an effect on graft composition. Thus, we analyzed the relationships between apheresis volume, graft composition, and transplantation outcomes in 142 consecutive patients undergoing unrelated donor allogeneic RIC HSCT. We found that apheresis volume ≥15 L was associated with a significantly decreased risk of relapse (adjusted hazard ratio [aHR], .48; 95% confidence interval [CI], .28 to .84]; P?=?.01) and improved relapse-free survival (aHR, .56; 95% CI, .35 to .89; P?=?.02) and overall survival (aHR, .55; 95% CI, .34 to .91; P?=?.02). A high apheresis volume was not associated with increased rates of acute or chronic graft-versus-host disease. These results demonstrate that an apheresis volume of at least 15 L is independently predictive of improved transplantation outcomes after RIC allogeneic HSCT.     

Cocaine and amphetamine attenuate the discriminative stimulus effects of naltrexone in opioid-dependent rhesus monkeys

This study tested the hypothesis that stimulants (indirect dopamine agonists) attenuate the discriminative stimulus of naltrexone in monkeys chronically treated with L-alpha-acetylmethadol (LAAM). Four rhesus monkeys (Macaca mulatta) received LAAM (1.0 mg/kg s.c.) twice daily and discriminated a withdrawal-precipitating dose of naltrexone (0.0178 mg/kg s.c.) from saline. Cocaine (0.1-1.78 mg/kg), amphetamine (0.32-1.78 mg/kg), haloperidol (0.01-0.1 mg/kg), sulpiride (1.0-10.0 mg/kg), propranolol (0.32-3.2 mg/kg), clonidine (0.001-0.1 mg/kg), desipramine (0.32-3.2 mg/kg), and imipramine (1.0-10.0 mg/kg) were given s.c. before cumulative doses of naltrexone. Cocaine and amphetamine antagonized the discriminative stimulus effects of naltrexone, each shifting the naltrexone dose-effect curve significantly (e.g., 100-fold) rightward or downward. In contrast, the dopamine antagonist haloperidol shifted the naltrexone dose-effect curve 5-fold leftward. Sulpiride, desipramine, clonidine, and propranolol had comparatively less effect on the naltrexone discriminative stimulus, whereas some doses of imipramine attenuated the naltrexone stimulus in a manner similar to that of cocaine and amphetamine. These results support the notion that multiple neurotransmitter systems are involved in the discriminative stimulus effects of opioid withdrawal. Furthermore, these data are consistent with reports that dopamine levels decrease during opioid withdrawal and provide evidence that enhancing dopamine or other monoamine levels may attenuate subjective effects of opioid withdrawal.     

The accuracy of assessment of walking distance in the elective spinal outpatients setting

Self reported walking distance is a clinically relevant measure of function. The aim of this study was to define patient accuracy and understand factors that might influence perceived walking distance in an elective spinal outpatients setting. A prospective cohort study. 103 patients were asked to perform one test of distance estimation and 2 tests of functional distance perception using pre-measured landmarks. Standard spine specific outcomes included the patient reported claudication distance, Oswestry disability index (ODI), Low Back Outcome Score (LBOS), visual analogue score (VAS) for leg and back, and other measures. There are over-estimators and under-estimators. Overall, the accuracy to within 9.14 metres (m) (10 yards) was poor at only 5% for distance estimation and 40% for the two tests of functional distance perception. Distance: Actual distance 111 m; mean response 245 m (95% CI 176.3–314.7), Functional test 1 actual distance 29.2 m; mean response 71.7 m (95% CI 53.6–88.9) Functional test 2 actual distance 19.6 m; mean response 47.4 m (95% CI 35.02–59.95). Surprisingly patients over 60 years of age (n = 43) are twice as accurate with each test performed compared to those under 60 (n = 60) (average 70% overestimation compared to 140%; p = 0.06). Patients in social class I (n = 18) were more accurate than those in classes II–V (n = 85): There was a positive correlation between poor accuracy and increasing MZD (Pearson’s correlation coefficient 0.250; p = 0.012). ODI, LBOS and other parameters measured showed no correlation. Subjective distance perception and estimation is poor in this population. Patients over 60 and those with a professional background are more accurate but still poor.     

Social regulation of serotonin in the auditory midbrain

The neuromodulator serotonin regulates auditory processing and can increase within minutes in response to stimuli like broadband noise as well as nonauditory stressors. Little is known about the serotonergic response in the auditory system to more natural stimuli such as social interactions. Using carbon-fiber voltammetry, we measured extracellular serotonin in the auditory midbrain of resident male mice during encounters with a male intruder. Serotonin increased in the inferior colliculus (IC) over the course of a 15 minute interaction, but not when mice were separated with a perforated barrier. Several behaviors, including the amount of immobility and anogenital investigation performed by the resident, were correlated with the serotonergic response. Multiple intrinsic factors associated with individual mice also correlated with the serotonergic response. One of these was age: older mice had smaller serotonergic responses to the social interaction. In a second interaction, individual identity predicted serotonergic responses that were highly consistent with those in the first interaction, even when mice were paired with different intruders. Serotonin was also significantly elevated in the second social interaction relative to the first, suggesting a role for social experience. These findings show that during social interaction, serotonin in the IC is influenced by extrinsic factors such as the directness of social interaction and intrinsic factors including age, individual identity, and experience.