A monoclonal antibody (RH1-38) which inhibits multiple systems of cell-mediated cytotoxicity--II. Evidence that the epitope recognized is involved in a late step in the cytolytic mechanism

A monoclonal antibody (RH1-38) which blocks multiple systems of cell-mediated cytotoxicity was functionally characterized. RH1-38 specifically blocks, in the absence of complement, natural killer (NK) activity (K562 targets) without any effect on NK-K562 conjugate formation. Kinetic studies suggested that the antibody blocks a step that occurs 30-120 min after effector populations are mixed with target cells. Single-cell cytotoxicity assays in agarose, combined with standard 51Cr release assays and Michaelis-Menten analysis revealed that RH1-38 markedly decreases Vmax and the number of active NK cells, again without any effect on the number of target-binding cells. The maximum recycling capacity was usually decreased, but in some experiments unchanged, in the presence of the monoclonal antibody. RH1-38 inhibited equally well whole peripheral blood mononuclear leukocytes (PBML), Percoll-fractionated lymphocytes enriched for NK activity, and interferon (IFN)-boosted NK activity. PBML exposed to RH1-38 and then washed mediated depressed NK activity which was partially reversed by subsequent treatment with IFN. These studies are most consistent with the hypothesis that RH1-38 inhibits a step late in the NK cytolytic mechanism rather than through an effect on conjugate formation. The primary effect is probably not on the IFN-generating or boosting mechanism, but a secondary effect on IFN-related mechanisms cannot be ruled out. Inhibition through an effect on a small lymphocyte modulator of NK activity is also unlikely but not rigorously excluded. Thus, RH1-38 appears to inhibit NK activity through a direct effect on NK effector cells, probably by interfering with a cell-surface molecule which is important in the expression of NK activity. The companion paper demonstrates that this monoclonal antibody immunoprecipitates a molecule which is very similar or identical to the LFA-1 antigen. Thus, RH1-38 recognizes either a novel epitope on the LFA-1 molecule or alternatively a distinct, functional killer cell surface molecule. The epitope appears to be involved in a late step in the cytolytic mechanism, possibly part of the effector cell lytic machinery.     

Virtual Reality Rehabilitation With Functional Electrical Stimulation Improves Upper Extremity Function in Patients With Chronic Stroke: A Pilot Randomized Controlled Study

Objective

To compare virtual reality (VR) combined with functional electrical stimulation (FES) with cyclic FES for improving upper extremity function and health-related quality of life in patients with chronic stroke.

Peer educator vs. respiratory therapist support: Which form of support better maintains health and functional outcomes following pulmonary rehabilitation?

Objective

This study examined if ongoing support delivered by telephone following pulmonary rehabilitation (PR) assisted chronic obstructive pulmonary disease (COPD) patients to maintain health outcomes.

Methods

Phase one (n = 79) compared post-rehabilitation telephone-based support delivered by peers compared to usual care (UC). The second phase (n = 168) compared post-rehabilitation support from peer educators, respiratory therapists (RT), or UC. Primary outcome variables were St. George's Respiratory Questionnaire (SGRQ) total score and the six minute walk test (6MWT). Measures were obtained at baseline, immediately following PR, and six-months post PR.

Results

Six-month follow-up data for phase one was collected for 66 COPD patients (n = 35 peer support, n = 31 UC) and 142 for phase two (n = 42 peer support, n = 52 RT support, n = 48 UC). Per-protocol and intention to treat (ITT) analysis in both phases found no significant group by time differences for SGRQ or 6MWT.

Conclusion

Providing peer or RT support via telephone following PR was not more effective than UC for maintaining health outcomes.

Practice implications

There are concerns with using peers to provide ongoing support to COPD patients. Additionally, COPD patients require a higher level of care than telephone support can provide.     

The efficiency of Gd‐EOB‐DTPA‐enhanced magnetic resonance cholangiography in living donor liver transplantation: a preliminary study

The aim of this study was to evaluate utility of gadoxetic acid disodium (Gd‐EOB‐DTPA)‐enhanced magnetic resonance cholangiography (MRC) for the detection of biliary complications after living donor liver transplantation (LDLT). A total of 18 patients with suspected biliary complications underwent MRC. T2‐weighted MRC and contrast‐enhanced MRC (CE‐MRC) were used to identify the biliary complications. MRC included routine breath‐hold T2‐weighted MRC using half‐Fourier acquisition single‐shot turbo spin‐echo (HASTE) sequences and Gd‐EOB‐DTPA‐enhanced MRC T1‐weighted volumetric interpolated breath‐hold examination (VIBE) sequences. Before confirming the biliary complications, one observer reviewed the MRC images and the CE‐MRC images separately. The verification procedures and MRC findings were compared, and the sensitivity, specificity, and accuracy of both techniques were calculated for the identification of biliary complications. The observer found six of seven biliary complications using CE‐MRC. The sensitivity was 85.7% and the accuracy was 94.4%. Using MRC alone, sensitivity was 57.1% and accuracy was 55.5%. The accuracy of Gd‐EOB‐DTPA‐enhanced MRC was superior to MRC in locating biliary leaks (p < 0.05). The usage of Gd‐EOB‐DTPA‐enhanced MRC yields information that complements the MRC findings that improve the identification of biliary complications. We recommend the use of MRC in addition to Gd‐EOB‐DTPA‐enhanced MRC to increase the preoperative accuracy when assessing the biliary complications after LDLT.     

Endocrinologic events in early pregnancy failure

Fourteen women experiencing early pregnancy failure have been studied during the time of conception and at frequent intervals until spontaneous abortion occurred. Serial measurements of serum estradiol, progesterone, 17α-hydroxyprogesterone, prolactin, human placental lactogen (hPL), and human chorionic gonadotropin (hCG) were determined; regular sonar scanning allowed the time of fetal death to be determined to within 7 days in six patients and a diagnosis of blighted ovum to be made in the remainder. In all patients serum progesterone and estradiol concentrations were within the normal range up to 7 weeks but appeared to decrease from about 8 weeks' gestation whether or not a living fetus was present. The placenta continued to produce hCG and hPL but, despite the continuing presence of hCG, the levels of 17α-hydroxyprogesterone declined to concentrations below those associated with normal pregnancy. These data suggest that the placenta may require a particular stimulus to take over production of progesterone and estradiol.     

Repeated administration of triiodothyronine (T3) to rats enhances nigrostriatal and mesolimbic dopaminergic behavioural responses

A once daily injection to rats of triiodothyronine (T₃; 100 μg/kg s.c.) for 10 days enhanced the locomotor responses of rats pretreated with tranylcypromine (5 mg/kg) to an injection into the nucleus accumbens of dopamine (5 μg bilaterally), when tested 24 hr after the last T₃ administration. This treatment did not, however, alter the control responses of tranylcypromine-pretrealed rats to injection of saline (1 μl bilaterally). Injection of T₃ for 10 days enhanced the circling responses of unilateral nigrostriatal-lesioned rats to apomorphine (0.5 mg/kg) but not to methamphetamine (0.5 mg/kg). The probable explanation for the latter result was the finding that repeated T₃ administration lowered basal striatal dopamine concentrations. The treatment also produced a trend towards reduced dopamine concentrations in the n. accumbens, although the difference did not reach statistical significance. These data suggest that repeated T₃ injection causes an increased post-synaptic function of both the nigrostriatal and mesolimbic dopamine systems in rat brain.