Identification of a graft versus host disease-associated human minor histocompatibility antigen

Minor histocompatibility antigen disparities between human leukocyte antigen (HLA)-matched bone marrow donors and recipients are a major risk factor for graft versus host disease (GVHD). An HLA-A2.1-restricted cytotoxic T cell clone that recognized the minor histocompatibility antigen HA-2 was previously isolated from a patient with severe GVHD after HLA-identical bone marrow transplantation. The HLA-A2.1-bound peptide representing HA-2 has now been identified. This peptide appears to originate from a member of the non-filament-forming class I myosin family. Because HA-2 has a phenotype frequency of 95 percent in the HLA-A2.1-positive population, it is a candidate for immunotherapeutic intervention in bone marrow transplantation.     

Transmitter amino acid release from rat neocortex: complete versus incomplete ischemia models

Release of the excitotoxic amino acids, glutamate and aspartate, from the ischemic rat cerebral cortex was compared in two models; the seven vessel occlusion model (7VO) of complete cerebral ischemia and the four vessel occlusion model (4VO) of incomplete cerebral ischemia. Amino acid efflux into cortical superfusates was measured using cortical cups placed on both hemispheres. Whereas a 20 min period of ischemia causes a pronounced release of glutamate and aspartate from the 4VO model, efflux was significantly reduced in the 7VO model. Release of the inhibitory transmitter GABA, was similar in the two models. This result suggests that excitotoxic amino acid efflux into the extracellular spaces of the cerebral cortex may be enhanced by the residual blood flow in an incomplete ischemia.     

A comparison of contextual and generalized auditory-cue fear conditioning: evidence for similar memory processes

A number of variables influence contextual, but not auditory-cue, fear conditioning. However, several of these variables (isolation, stimulus preexposure, retention interval, and age) affect generalized auditory-cue fear. More generalized fear was found when (a) rats were isolated in a novel environment than when returned to their home cages, (b) the retention interval was 3 hr rather than 24 hr, and (c) in 18-day-old compared with 25-day-old rats. Moreover, preexposure to the auditory cue eliminated the isolation effect. At a behavioral-psychological level, these variables may exert their effects by influencing the processes that construct a memory representation of the stimulus. At a neural systems level, they may influence processing carried out in the thalamo-corticoamygdaloid auditory pathway.     

Localization of tumor-reactive lymph node lymphocytes in vivo using radiolabeled monoclonal antibody

BACKGROUND: Lymph node lymphocytes vary in their responsiveness to tumor. A technique has been developed that uses radiolabeled monoclonal antibody (MoAb) against the tumor-associated mucin, TAG-72, and a gamma-detecting probe by which lymph nodes containing microscopic tumor and/or shed TAG-72 can be identified in vivo. The immunologic characteristics of these lymph nodes were examined. METHODS: Patients with colon cancer received 125I-labeled MoAb CC49 by intravenous injection preoperatively. During laparotomy lymph nodes that appeared normal on inspection and palpation but which contained radiolabeled MoAb were identified using a hand-held gamma-detecting probe. These lymph nodes and other lymph node and tumor specimens were resected for analysis. RESULTS: Lymph nodes identified by the probe were found by immunohistochemical studies to contain microscopic tumor and/or shed antigen associated with germinal centers. They were characterized by greater CD4+:CD8+ ratios, rates of expansion, and cytolytic activity compared with lymphocytes from lymph nodes with macroscopic tumor, noninvolved lymph nodes, and tumors. All lymph node lymphocytes identified by the probe demonstrated significant proliferative responses to autologous tumor and, in contrast to lymphocytes from noninvolved lymph nodes, significant proliferative responses to allogeneic TAG-72+ tumor cells and to soluble TAG-72+ mucin. CONCLUSIONS: By locating lymph nodes with microscopic tumor and/or shed antigen, the use of radiolabeled MoAb in vivo can be used to reproducibly identify tumor-reactive lymph node lymphocytes. This technique may be useful in identifying cells for use in adoptive immunotherapy programs and in studying the regulation of immune responses in vivo.     

Medical versus surgical management of diverticulitis in patients under age 40

BACKGROUND: Diverticulitis in patients under age 40 is a distinct entity. We compared the medical versus surgical management of diverticulitis for complications and outcomes in these patients. METHODS: A retrospective review was performed for treatment, hospitalizations, complications, and outpatient visits. Complications included readmission, recurrent symptoms after antibiotic therapy, and postoperative problems. RESULTS: Twenty-nine patients had a radiographic or surgical diagnosis of diverticulitis (18 surgical, 11 medical). Medically managed patients had significantly more emergency department visits (4.7 +/- 6.6 versus 0.3 +/- 0.6, P < or =0.01), and readmissions (7 versus 4, P < or =0.02). Three surgical patients (17%) had a total of 6 complications as compared with 6 medical patients (55%) with 25 complications (chi square, P < or =0.05). All medically treated patients had recurrent symptoms, and 6 required surgery. CONCLUSION: Medically managed patients had significantly more emergency department visits and complications than those managed surgically. Surgery is the indicated treatment for the first episode of diverticulitis in patients under age 40.