Occurrence of the t(2;5)(p23;q35) in non-Hodgkin's lymphoma

Primary CD30(Ki-1)-positive anaplastic large-cell lymphoma (ALCL) is considered by some to be a distinct clinicopathologic entity associated with the t(2;5) (p23;q35). However, the specificity of t(2;5) for ALCL has not been carefully studied. Therefore, we performed a detailed analysis of all cases of ALCL with abnormal cytogenetics results in the Nebraska Lymphoma Study Group registry, as well as all other cases of non-Hodgkin's lymphoma with t(2;5) in the registry. We found the t(2;5) in only five of 10 cases of ALCL, four of whom were young patients. However, we also found the t(2;5) in 11 other cases of nonanaplastic lymphoma, including eight children with typical peripheral T-cell lymphomas of various types. The t(2;5) was also found in three older adults with B-cell lymphomas of various types. Thus, the t(2;5) was not specific for CD30+ ALCL. However, t(2;5) may define a clinicopathologic entity in children and young adults characterized by variable morphologies with a T-cell or indeterminate phenotype, CD30-positivity, nodal disease with frequent extranodal involvement, advanced stage, and an excellent response to therapy, including bone marrow transplantation for relapsed disease. The clinical relevance of the t(2;5) in older patients requires further study.     

Dural sinus thrombosis: study using intermediate field strength MR imaging

The magnetic resonance (MR) images of six patients with thrombosis of a dural sinus were reviewed. The diagnosis had been verified by computed tomographic scans in three patients and arteriograms in two; in the sixth patient, only MR imaging was used to confirm the clinical syndrome. In all patients, high-intensity signal was seen from the thrombus within the affected dural sinus on all echoes. This persistent signal intensity allowed intravascular clot to be distinguished from normal causes of increased signal such as flow-related enhancement (entry phenomenon) and even-echo rephasing. MR imaging demonstrated the cause of the thrombosis in three patients: two were secondary to adjacent tumors, and one was secondary to unsuspected mastoiditis. Complications such as infarction were also demonstrated. Using MR imaging, one can easily and safely diagnose thrombosis of a dural sinus. MR should be the imaging method of choice in patients suspected of having thrombosis of a dural sinus.     

Clinical MR imaging with a Helmholtz-type surface coil

Limited-field-of-view radio-frequency receiver antennas provide improved near-field sensitivity for magnetic resonance imaging by decreasing the antenna volume. The Helmholtz-type surface coil, consisting of two flat rings, is an organ-encompassing antenna that takes advantage of this principle to yield an improved signal-to-noise ratio (S/N). The coil was tested in a group of 50 patients and 16 healthy volunteers. Images obtained with the Helmholtz coil demonstrated quantitatively superior S/N of 2.2-fold or greater than that of comparison body coil images, as well as qualitatively superior anatomic resolution.     

Effect upon the EEG of acute injury to the brain stem activating system

The effect upon the EEG in the unanesthetized "ecéphale isolé" of acute brain stem lesions in a position to involve the ascending reticular activating system has been studied. Elimination of the bulbar segment was without marked effect. Some synchronization followed elimination of the pons, but the most pronounced and prolonged changes occurred as a result of mesencephalic transection, or of discrete injury to the midbrain tegmentum or basal diencephalon, following which the EEG activation pattern of low voltage fast activity was reduced or abolished and the cortical record became dominated by recurring bursts or spindles of high voltage slow waves like those of normal sleep or barbiturate anesthesia. Bursts could be recorded from the intralaminar and other nuclei of the thalamus and these thalamic bursts were abolished by acute decortication. Conversely, cortical bursts were abolished by acute thalamic lesions. Possible interrelations of these regions in this activity is discussed. These results offer an explanation for the clinical observation of somnolence following basal injury to the brain, and suggest that a maintained influence of the ascending brain stem activating system underlies wakefulness, while absence of this influence precipitates sleep.     

Low-artifact intravascular devices: MR imaging evaluation

Flow-phantom magnetic resonance (MR) imaging, with use of both spin-echo (SE) and gradient-echo (GRE) techniques at 1.5 T, was performed on the percutaneous Greenfield (beta-III titanium alloy [TMA wire]), Amplatz (MP32-N alloy), and Simon nitinol filters and TMA wire facsimiles of the bird's nest, Gunther, new retrievable, and Amplatz vena caval filters. SE imaging allowed detection of thrombi as small as 5 X 5 mm trapped within the percutaneous Greenfield, Simon nitinol, and TMA-wire facsimile filters; with the MP32-N Amplatz filter, a larger volume of thrombus (10 X 20-mm clots) was necessary for clot detection. GRE imaging allowed detection of intraluminal tilting of the percutaneous Greenfield and facsimile Amplatz (TMA-wire) filters. GRE imaging was useful for demonstrating postfilter turbulence due to clots, which was greatest for the Amplatz filter. Imaging of facsimile vascular devices made of tantalum or TMA wire did not cause the severe "black-hole" MR artifacts typical of the stainless-steel devices. SE and GRE imaging were very useful for determining caval patency in two patients with previously placed Mobin-Uddin filters. Noninvasive MR evaluation of blood vessels in the presence of a variety of low-artifact intravascular devices appears feasible.     

Coexpression of class I major histocompatibility antigen and viral RNA in central nervous system of mice infected with Theiler's virus: a model for multiple sclerosis.

Chronic infection of susceptible strains of mice with Theiler's murine encephalomyelitis virus (TMEV) results in central nervous system (CNS) demyelination similar to multiple sclerosis. Demyelination induced by TMEV is mediated, in part, by class I-restricted CD8+ T lymphocytes. For these T cells to function, they must recognize virus-infected CNS targets in the presence of class I major histocompatibility complex (MHC) antigen. Therefore, we studied in vivo expression of class I MHC antigen and viral antigen-RNA in prototypic mouse strains that are susceptible (SJL/J) or resistant (C57BL/10SNJ) to TMEV-induced demyelination. In brains of resistant mice, viral antigen-RNA expression peaked on day 3 after infection and was effectively diminished by day 5 such that few virus-infected cells were ever detected in the spinal cord. In contrast, susceptible mice demonstrated delay in clearance of TMEV from the brain and a subsequent increase and persistence of viral antigen-RNA in the spinal cord for as long as 277 days. Viral infection resulted in "upregulation" of class I MHC expression in the CNS. Class I MHC antigens were expressed as early as 1 day after infection in the choroid plexus of both strains of mice before detection of viral antigen or inflammation. In resistant mice, class I MHC expression predominated in the gray matter of the brain and spinal cord on day 7 after infection but returned to undetectable levels by day 28. In susceptible mice, class I MHC expression in the CNS persisted and was intense in the white matter of the spinal cord throughout chronic infection and demyelination. No class I MHC expression was detected in the CNS of uninfected mice. Coexpression of viral RNA and class I MHC antigen was demonstrated in CNS cells by using simultaneous in situ hybridization and immunoperoxidase technique. These results support the hypothesis that a class I-restricted immune response directed against virus-infected cells may be important in the mechanism of demyelination.     

Detection and composition of immune complexes in experimental African trypanosomiasis.

Humoral immune responses in experimental African trypanosomiasis were assessed in rabbits infected with Trypanosoma rhodesiense. Immune complexes as measured by a Clq binding assay or a Clq solid-phase assay were detected by day 10 and increased progressively through day 28. Immune complexes analyzed by double diffusion in agar or enzyme immunoassay contained immunoglobulin M (IgM) and IgG consistently, and usually C3. In one serum, immune complexes contained trypanosomal antigens in addition to C3, IgG, and IgM. By sucrose density gradient ultracentrifugation Clq-binding immune complex-like materials were shown to contain IgG, IgM, and C3, sedimentating as intermediate (between 7S and 19S) or as higher-molecular-weight (greater than 19S) aggregates. Serum IgM and IgG antibodies to trypanosomes were measured by enzyme immunoassay. IgM antibodies were detected by day 7, rose to peak by day 14, and declined slowly thereafter. IgG antibodies were detected by day 14 and continued to rise through day 32. Total IgM and IgG measured by radial immunodiffusion paralleled the corresponding changes in antibody levels. Host immune responses, in part directed to trypanosomal antigens, produced circulating immune complexes containing bound C3; these may be deposited in tissue or may serve as a serological marker of immune complex-mediated tissue injury.     

Intradimerically tethered DNA topoisomerase II is catalytically active in DNA transport.

A covalently cross-linked dimer of yeast DNA topoisomerase II was created by fusing the enzyme with the GCN4 leucine zipper followed by two glycines and a cysteine. Upon oxidation of the chimeric protein, a disulfide bond forms between the two carboxyl termini, covalently and intradimerically cross-linking the two protomers. In addition, all nine of the cysteines naturally occurring in topoisomerase II have been changed to alanines in this construct. This cross-linked, cysteine-less topoisomerase II is catalytically active in DNA duplex passage as indicated by ATP-dependent DNA supercoil relaxation and kinetoplast DNA decatenation assays. However, these experiments do not directly distinguish between a "one-gate" and a "two-gate" mechanism for the enzyme.