Gliotoxicity, reverse transcriptase activity and retroviral RNA in monocyte/macrophage culture supernatants from patients with multiple sclerosis

Utilizing cultured lenses from normal and homozygous glutathione peroxidase (GSHPx-1) knockout mice and inhibitors for GSSG Reductase (GSSG Red), 1,3-bis(2-chlorethyl)-1-nitrosourea (BCNU) and catalase (Cat), 3-aminotriazole (3-AT), the ability to degrade H2O2 was examined at two H2O2 concentrations, 300 microM and 80 microM. It was found that GSHPx-1 contributed about 15% to the H2O2 degradation. The Cat contribution was concentration dependent being about 30% at 300 microM H2O2 and approximately 8% to 15% at 80 microM H2O2. GSH loss measured as nonprotein thiol (NP-SH) was shown to be linked to most of the remaining H2O2 degradation accounting for about 54% to 72% of the H2O2 degradation at 300 microM and 80 microM, respectively. However, based on evaluation of the ability of GSH to nonenzymatically degrade H2O2, it can only account for about 36% at 300 microM and 19% at 80 microM H2O2 of the observed lens H2O2 degradation. It is, therefore, concluded that lens GSH must be involved in other reactions either directly or indirectly related to H2O2 degradation.     

Interleukin-12 induces relapse in experimental allergic encephalomyelitis in the Lewis rat

Acute, monophasic experimental allergic encephalomyelitis (EAE) in the Lewis rat shows pathological similarities to the human disease multiple sclerosis (MS). Rats that recover from EAE are essentially resistant to disease reinduction, unlike MS in which relapses are frequently associated with common bacterial and viral infections. As macrophage-derived interleukin (IL)-12 is a critical component of innate resistance to bacterial infection and appears to directly activate encephalitogenic T cells in vivo, the ability of this cytokine to reinduce paralysis in EAE was examined. Paralytic disease was exacerbated by intraperitoneal IL-12 administration and could be reinduced up to 1 week after recovery from the primary clinical episode. Concomitant with worsening of initial clinical signs and relapse was an increase in the ratio of macrophages to T cells in brain stem perivascular cuffs and the expression of inducible nitric oxide synthase in cells with both macrophage and microglial morphology. These findings suggest that IL-12 may contribute to macrophage-mediated disease exacerbation and relapse in patients with MS.     

Zoonotic Brugian lymphadenitis. An unusual case with florid monocytoid B-cell proliferation

Human infection with a zoonotic Brugia species in the United States is uncommon. Positive identification of the filarial nematode is required for histopathologic diagnosis. Many cases may go unrecognized because of the nonspecific clinical manifestations and the nondiagnostic histologic changes occurring in involved lymph nodes. A case of zoonotic Brugia lymphadenitis is described in a patient from Rhode Island, in which a small nongravid female worm was identified in a lymph node biopsy specimen. The lymph node also showed a spectrum of reaction changes including the presence of florid monocytoid B-cell proliferation, which has not been described in association with zoonotic Brugian filariasis.     

Management of lymphoproliferative disorders after cardiac transplantation

We conducted a retrospective study of 516 cardiac recipients who underwent transplantation between April 1983 and April 1992, 19 of whom had development of post-transplantation lymphoproliferative disorders (PTLDs). These 19 patients presented with involvement of lung (5), gastrointestinal tract (5), disseminated disease (6), and adenoids and lymph nodes (3). B-cell proliferations ranging from an atypical hyperplasia to malignant lymphoma developed in 18 patients, and mixed cellularity Hodgkin's disease developed in 1 patient. The 19 patients with PTLD displayed a predominance of both women and cardiomyopathy as the indication for transplantation when compared with two separate control populations. No correlation was found between demographic criteria analyzed and (1) early versus late diagnosis of PTLD after transplantation, (2) the site of PTLD involvement, or (3) the histopathologic category of the PTLD lesion. Patients with gastrointestinal tract and lung PTLD involvement enjoyed an improved survival after both transplantation and PTLD diagnosis when compared with patients with PTLD involvement of all other extranodal sites. We report a high incidence of PTLD involving the lung and gastrointestinal tract in our cohort study. These sites of involvement responded better to a reduction in immunosuppression than did the other extranodal sites of involvement.     

Prevalence of serologic markers of HBV, HDV, HCV and HIV in non-injection drug users compared to injection drug users in Gran Canaria, Spain

Von Hippel-Lindau disease (VHL) is an autosomal dominant tumour syndrome caused by germline mutations of the VHL tumour suppressor gene located on chromosome 3p25-26. In VHL tumours may occur in 14 different target organs, including the eye. Retinal angiomas are considered the first manifestation of VHL disease in 43% of cases, and the cumulative probability of developing a retinal angioma in one or both eyes rises during each decade of life, reaching 80% for patients over 80 years old. Since 1976 patients with VHL at the University Hospital of Utrecht and their at-risk relatives have been screened periodically by a multidisciplinary team. Long-term follow-up ophthalmological data were analysed with special attention to natural course and results of treatment. In addition, we looked for a genotype-phenotype correlation. Retinal angiomas were found in all families. In one large family with a missense mutation (V170D) of the VHL gene, in which the complete spectrum of visceral- and central nervous system (CNS) features of VHL is present, macular, parapapillary, optic disc and ora serrata angiomas were also found. In general, however, a clear-cut genotype-phenotype correlation could not be found. Only early detection and treatment of peripheral retinal angiomas can be expected to decrease the percentage of patients with decreased visual acuity. Therefore, early detection and treatment of these tumours is of paramount importance. Ophthalmological screening of patients and persons at risk should start as early as possible. In patients with apparently sporadic retinal angiomas it is advisable to perform germline DNA analysis, since the risk of developing VHL is high, especially if the angiomas are bilateral, or unilateral and multifocal, if the patient is young, or if there is a family history suggestive of VHL.