Use of reinduced experimental autoimmune encephalomyelitis to evaluate the importance of epitope spread

Several investigators have reported experimental evidence of epitope spreading in experimental autoimmune encephalomyelitis (EAE). The role of epitope spreading in the pathogenesis of relapsing or chronic autoimmune disease is not established and the in vivo function of the T cells specific for new epitopes which appear during an autoimmune response is unclear. We recently demonstrated that mice which have recovered from an episode of EAE suffer a relapse shortly after reinjection with the original encephalitogen. The reinduced disease occurs in a reproducible fashion with an accelerated onset. This may be due to persistence of an expanded population of previously activated encephalitogenic cells which are rapidly reactivated when re-exposed to antigen. We reasoned that if epitope spread produces a significant number of encephalitogenic cells specific for a new epitope, then reinjection with that epitope should also cause the rapid onset of an episode of EAE. We tested this hypothesis using the known encephalitogenic epitopes in SJL mice. After recovery from EAE induced with the proteolipid protein peptide PLP139-151, five of 16 mice had an accelerated relapse of EAE when reinjected with a second encephalitogenic peptide, PLP178-191. All of the 10 mice reinjected with the original PLP139-151 peptide relapsed. We conclude that epitope spread may produce encephalitogenic cells specific for new epitopes, but that the response to new epitopes is minor compared to the response to the initial epitope.      

Focal nodular hyperplasia and hepatic adenoma: comparison of angiography, CT, US, and scintigraphy

The authors reviewed 23 cases of focal nodular hyperplasia and 13 cases of hepatic adenoma, all of which were confirmed pathologically. All solitary masses that exhibited normal or increased uptake of technetium 99m-sulfur colloid were shown to be hyperplasia; while previous criteria such as a central blood supply on angiograms or a central scar on computed tomography (CT) or ultrasound (US) scans were helpful, they were relatively infrequent. A mass that was slightly hypodense and homogeneous on a CT or US scan and highly vascular with an intense capillary stain on an angiogram was almost always hyperplasia. Acute hemorrhage within a focal hepatic tumor was common in adenoma but did not occur in hyperplasia.     

Malignant melanoma of the eye: treatment of posterior uveal lesions by Co-60 plaque radiotherapy versus enucleation

Survival rates and visual acuity of 100 patients treated for posterior uveal malignant melanoma by cobalt-60 plaque radiotherapy were compared with 150 patients treated by enucleation for the same disease. Life-table comparisons of the entire group showed significant differences in survival rates, with plaque radiotherapy patients appearing to fare better. However, when patients with small or medium tumors were compared, only slight differences were seen, implying that criteria used to select patients for treatment may affect interpretation. The two groups were also compared using the Cox proportional hazards model, which predicts survival based on the impact of clinical variables. In this analysis, the survival rates of the plaque radiotherapy group were no worse than those of the enucleation group. The advantage of conservative therapy lies in the potential to preserve useful vision over a considerable time. Because patients were specifically selected for treatment modality and because the study size used to calibrate the Cox model was small, the results of this study must be interpreted with caution.     

Impact of blood transfusion and burn injury on microbial translocation and bacterial survival

The role of the immune system in microbial translocation must be clarified. In these studies, the effect of blood transfusion-related immunosuppression on translocation was investigated in a burn animal model previously known to increase the gut's permeability to 14C-radiolabeled Escherichia coli. In a first experiment, Balb/c mice underwent transfusion (T) with 0.2 mL per mouse of allogeneic C3H/HeJ mouse blood 5 days prior to undergoing 30-percent burn injury (B) and simultaneous gavage (G) with 10(9) E. coli bacteria labeled with 14C. An additional six groups of Balb/c mice underwent different combinations of T, B, and G procedures (TG, BG, TB, T, B, G). Survival rate was recorded for all groups on Day 10. This experiment suggested that B and T, to a lesser extent, were the factors affecting survival, although the combination of T, B, and G clearly showed a synergistic effect on mortality. In a second experiment, 18 Balb/c mice belonging to TBG, BG, TG, and G groups were sacrificed 1, 4, and 24 hours after burn or gavage. The residual radioactivity and the percentage of viable bacteria were computed for mesenteric lymph nodes, spleen, liver, lungs, blood, and peritoneal fluid. Statistical analysis of the radionuclide counts recognized B as the only variable able to enhance the magnitude of 14C E. coli translocation. The percentage of viable bacteria showed that T and, more moderately, B were the factors leading to the failure of bacterial clearance in the tissues.     

Antibody stimulation of hemopoietic progenitor cells

Antisera were raised by immunizing rabbits with cloned lines of murine hemopoietic progenitor cells (P cells) that depended on the presence of a specific hemopoietic growth factor, persisting cell-stimulating factor (PSF), for their growth and survival. The unabsorbed antiserum was inhibitory, but after absorption with murine spleen cells and the mastocytoma, P815, significant stimulation of both P cell growth and thymidine incorporation was evident. IgG antibodies isolated from the antiserum by staphylococcal protein A chromatography or further purified by diethylaminoethyl anion exchange chromatography, ammonium sulphate precipitation, and gel filtration using Sephacryl S-300 were responsible for the stimulation. The absorbed antiserum promoted the survival of normal murine bone marrow cells in liquid culture over a four-day period, and the inclusion of IgG antibodies in agar cultures of normal bone marrow promoted the in vitro survival, over a 48-hour period, of cells capable of subsequently generating, in the presence of a source of PSF, colonies of neutrophils, macrophages, and megakaryocytes. It is postulated that the antibodies act by stimulating the PSF receptor on both the factor-dependent cell lines and normal myeloid progenitor cells.     

Idiotype profile of an immune response. I. Contrasts in idiotypic dominance between primary and secondary responses and between IgM and IgG plaque- forming cells

The primary response of A/J mice to p-azobenzenearsonate-keyhole limpet hemocyanin (ABA-KLH) was investigated. A day-by-day analysis at the plaque- forming cell (PFC) level was performed, with inhibition by anti-cross- reactive idiotype (CRI) serum to determine percentage of CRI(+) PFC. A regular pattern in the dynamics of Id (idiotype) dominance was observed. Just as in the NP-b and NP-a systems (9, 12), the major Id (CRI) is more dominant in primary than in secondary or hyperimmune responses. This trend is more apparent in IgG PFC which are generally 80-95 percent CRI(+) at day 10 in the primary response but only 30-40 percent CRI(+) at day 10 in secondary or hyperimmune responses. A somewhat different pattern is seen with IgM PFC. These may reach a peak of 85 percent CRI(+) in the primary response, but secondary or hyperimmune IgM PFC, which are lower in numbers than IgG PFC, remain high in CRI content at approximately 70 percent. The PFC data on extent of id dominance in secondary or hyperimmune responses is fully compatible with previously reported serological data by others. Analysis of IgG PFC by hapten inhibition indicated that heterogeneity was in the order secondary PFC {greater than} primary PFC {greater than} hybridoma AK-2.2 PFC with H(75)/H(25) values of 22.9, 6.2, and 2.7, respectively; where H(75) and H(25) are the hapten concentrations required to give 75 percent and 25 percent of inhibition of PFC, respectively. Hapten inhibition data also suggested that secondary IgG PFC were 10 times higher in median binding avidity for ABA-L-tyrosine than primary IgG PFC. The kinetic analysis strongly indicated that CRI(+) IgM PFC were preferentially switched to IgG PFC in the primary response. In both studies, the CRI content of the earliest-appearing IgG PFC was significantly higher than that of IgM PFC on that day. For example, in one case IgM PFC were 60 percent CRI + on day 6 whereas IgG PFC were 100 percent CRI(+). The high Id dominance and selective isotype switching may have either a B or a T cell basis.     

Hangman's fracture: radiologic assessment in 27 cases

Traumatic spondylolisthesis of C-2, frequently referred to as the hangman's fracture, is typically regarded as a hyperextension injury with rare neurologic sequelae by virtue of decompression of the neural canal. The authors retrospectively evaluated their radiographic experience with this injury in 27 patients over a 24-month period. Lateral cervical spine studies and computed tomography (CT) scans (21 patients) were analyzed. CT studies provided better delineation of the fracture in all 21 patients and significant additional information in five patients (24%). Seven patients (26%) suffered initial neurologic sequelae in association with the C-2 injury. Nine patients had additional sites of fracture, including seven with associated C-1 ring disruption (26%). Extension of the fracture line into the transverse vertebral artery foramen led to vertebral artery injury and cerebellar embolization in one patient. Angiography may be necessary to detect intimal injury to the vertebral arteries when the fracture extends through the transverse foramina and to indicate the need for anticoagulation when clinically feasible.