Usefulness of contrast material in MR of patients with neurofibromatosis type 1.

PURPOSEOur objective was to determine the usefulness of routine administration of contrast material in brain MR imaging for the evaluation of areas of probable myelin vacuolization and neoplasms in patients with neurofibromatosis type 1 (NF-1).METHODSWe retrospectively reviewed 112 consecutive contrast-enhanced brain MR studies obtained over a period of 7 years in 109 symptomatic and asymptomatic patients compiled from two institutional NF-1 data bases. MR studies were analyzed for areas of probable myelin vacuolization, with attention to degree of enhancement and its impact on lesion detection and characterization. Usefulness of contrast material was graded as 0 = not useful, 1+ = somewhat useful, and 2+ = useful.RESULTSOf 112 studies, 45% (n = 49) were normal. In the remaining 63 studies, 88 regions of probable myelin vacuolization and 52 tumors were identified. Enhancement was not observed in any regions of probable myelin vacuolization. Enhancement was present in 31% of tumors, and, of these, was found to be useful in 44%, somewhat useful in 12%, and not useful in 44%. For enhancing tumors, contrast agent was useful for lesion detection in 19% and for lesion characterization in 25%.CONCLUSIONContrast administration is useful in baseline MR studies to maximize tumor detection and characterization, to add confidence to the diagnosis of benign probable myelin vacuolization, and to document stability of neoplasms on follow-up examinations.     

Anti-tumor effect of tumor necrosis factor and its induction of tumor variant of MBT-2 transitional cell carcinoma of the bladder

The effect of tumor necrosis factor (TNF), a potential anti-tumor agent, was assessed both in vivo and in vitro against MBT-2 transitional cell carcinoma of the bladder in C3H/HeHa mice. Systemic administration of either single or multiple doses of TNF into tumor bearing animals resulted in partial tumor regression and had a consistent but transient anti-tumor effect. Compared to control, untreated tumor bearing animals, TNF-treated tumor bearing mice had significantly smaller tumor volumes and slower tumor growth rates over the period of 12 days following TNF inoculation. No significant difference in tumor volumes and tumor growth rates between controls and TNF-inoculated mice was observed from day 12 to day 21 after TNF treatment. Assessment of TNF cytotoxicity against in vitro MBT-2 cell line using 3[H]-thymidine proliferation assay showed significant sensitivity of MBT-2 cells to treatment with TNF. A "Variant" MBT-2 cell line was derived by sequential culturing of the original MBT-2 cells in the presence of progressively higher concentrations of TNF in culture medium. Although the significant growth suppression on the MBT-2 tumor appears to be transient, further studies are warranted which may elucidate the immunologic and biologic behavior of TNF and this transplantable animal tumor.     

β-Methyl-15-p-iodophenylpentadecanoic acid metabolism and kinetics in the isolated rat heart

The use of 15-p-iodophenyl--methyl-pentadecanoic acid (Me-IPPA) as an indicator of long chain fatty acid (LCFA) utilization in nuclear medicine studies was evaluated in the isolated, perfused, working rat heart. Time courses of radioctivity (residue curves) were obtained following bolus injections of both Me-IPPA and its straight chain counterpart 15-p-iodophenyl-pentadecanoic acid (IPPA). IPPA kinetics clearly indicated flow independent impairment of fatty acid oxidation caused by the carnitine palmitoyltransferase I inhibitor 2[5(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA). In contrast, Me-IPPA kinetics were insenstive to changes in fatty acid oxidation rate and net utilization of long chain fatty acid. Analysis of radiolabeled species in coronary effluent and heart homogenates showed the methylated fatty acid to be readily incorporated into complex lipids but a poor substrate for oxidation. POCA did not significatly alter metabolism of the tracer, suggesting that the tracer is poorly metabolized beyond Me-IPPA-CoA in the oxidative pathway.     

Radiation-induced lung injury in vivo: Expression of transforming growth factor—Beta precedes fibrosis

Cytokine release from irradiated cells has been postulated to start soon after irradiation preceding detectable clinical and pathological manifestation of lung injury. The expression of transforming growth factor beta (TGF), a fibrogenic and radiation-inducible cytokine, was studied from 1–16 weeks after the 15 and 30 Gray (Gy) of thoracic irradiation to rats. Thoracic irradiation caused an increase in TGF protein in bronchoalveolar lavage (BAL) fluid peaking at 3–6 weeks as compared to sham-irradiated control rats. Steady state TGF mRNA expression as shown by whole lung northern blot assay paralleled the TGF protein expression in BAL fluid. The peak of TGF protein increase in BAL fluid between 3 and 6 weeks coincided with the initial influx of inflammatory cells in BAL fluid, but preceded histologically discernable pulmonary fibrosis that was not apparent until 8–10 weeks after irradiation. In conclusion, TGF and mRNA and protein upregulation preceded the radiation-induced pulmonary fibrosis, suggesting a pathogenetic role in the development of radiation fibrosis.     

Signaling via LTbetaR on the lamina propria stromal cells of the gut is required for IgA production

Peyer's patches (PPs) and/or mesenteric lymph nodes (MLNs) are thought to be essential for immunoglobulin A (IgA) production. We found that the severe IgA deficiency in lymphotoxin-deficient (LT(-/-)) mice could be fully reversed by reconstitution with LT-expressing bone marrow, despite the absence of both LNs and PPs. The number of IgA precursors from LT(-/-) mice was not reduced, and they were able to migrate into the lamina propria (LP) of wild-type mice but not of LTbetaR(-/-) mice. Consistently, lymphoid tissue chemokines and adhesion molecules were reduced within the LP of LTalpha(-/-) and LTbetaR(-/-) mice. IgA deficiency in LTalpha(-/-) mice was reversed by the transplantation of a segment of RAG-1 (recombination-activating gene 1) deficient intestine, which confirmed the dispensability of the MLNs and PPs and the sufficiency of the LT-mediated gut microenvironment for IgA production.     

Creutzfeldt-Jakob disease (CJD) with a mutation at codon 148 of prion protein gene: relationship with sporadic CJD

Creutzfeldt-Jakob disease (CJD), the most common human prion disease, includes sporadic (s) and familial (f) forms. Regardless of etiology, both forms are thought to share the pathogenic mechanism whereby the cellular prion protein (PrP(C)) converts into its pathogenic isoform (PrP(Sc)). While PrP(C) conversion is thought to be random in sCJD, conversion in fCJD is facilitated by the congenital presence of mutated PrP. Differences in PrP genotype (PRNP) and in conversion circumstances lead to PrP(Sc) with distinct characteristics that elicit different disease phenotypes. Here, we describe a case of fCJD with a substitution of histidine (H) for arginine (R) at codon 148 (R148H) and heterozygosity of the methionine/valine (M/V) polymorphic codon 129, with the 129M allele coupled with the mutation. The disease phenotype and all major characteristics of PrP(Sc) of fCJD(R148H) were virtually indistinguishable from those of sCJDMV2, which has features different from those of any other sCJD. Therefore, despite the differences in etiology, PRNP, and conversion process, the two forms of PrP(Sc) had similar characteristics. Furthermore, comparison of fCJD(R148H) with a recently reported case carrying R148H and homozygosity at codon 129 suggests that codon 129 coupled with the mutation as well as that located on the normal allele can modify major phenotypic and PrP(Sc) features of fCJD(R148H).