Encephalitogenic and tolerogenic potential of altered peptide ligands of MOG and PLP in Biozzi ABH mice

Altered peptide ligands (APL) are highly effective in inhibiting experimental autoimmune encephalomyelitis (EAE) in rodents although clinical trials in multiple sclerosis reveal severe limitations probably due to the diverse and differential effects of APL in vivo compared to in vitro. Myelin oligodendrocyte glycoprotein (MOG 8-21) induces relapsing EAE in ABH (A(g7)) mice associated with broadening of the autoimmune repertoire thus providing a dynamic system to examine the efficacy of peptide analogues. Subtle changes in MOG 8-21 dramatically influenced disease susceptibility and T cell responses in vitro. Non-encephalitogenic APL that induce production of the 'regulatory' cytokines IL-10 and/or TGFbeta and concomitant low levels of the 'proinflammatory' cytokines IFNgamma and TNFalpha modulated relapsing EAE but were far less effective than the 'proinflammatory' wild-type MOG 8-21 peptide. These data reveal that APL differ greatly in their ability to activate encephalitogenic T cells. The extensive heterogeneity of responses of APL in vitro suggests that selection of APL on this criteria is highly unpredictable and probably less effective for therapy than selecting the dominant wild-type epitope and delivering it using a tolerogenic route.     

Biozzi mice: of mice and human neurological diseases

In 1972 Guido Biozzi selectively bred mice to study the immunopathological mechanisms underlying polygenic diseases. One line, the Biozzi antibody high (AB/H) mouse (now designated the ABH strain) was later found to be highly susceptible to many experimentally induced diseases such as autoimmune encephalomyelitis, autoimmune neuritis, autoimmune uveitis, as well as virus-induced demyelination and has thus been a key mouse strain to study human inflammatory neurological diseases. In this paper we discuss the background of the Biozzi ABH mouse and review how studies with these mice have shed light on the pathogenic mechanisms operating in chronic neurological disease.     

Genital leiomyoma: surgical excision for both diagnosis and treatment of a unilateral leiomyoma of the male nipple

We describe a rare case of unilateral leiomyoma of the nipple in a man presenting with pruritus of the nipple for 3 months. A conservative surgical excision is performed for diagnosis. Histologic examination and immunostaining confirmed the diagnosis of leiomyoma. The leiomyoma is completely excised, and the patient denies pruritus after surgery. Conservative surgical excision of a persistently hard and pruritic nipple can be effectively used as both diagnostic measure and treatment modality.     

Angiosarcoma: a case report and review of the literature

Angiosarcoma is an aggressive neoplasm that predominantly affects elderly patients. Most cases appear on the scalp and face de novo; however, trauma, longstanding lymphedema, and irradiation are predisposing factors. Management includes a multidisciplinary team and may involve a combination of surgery, radiation, and chemotherapy tailored to the patient's age and associated comorbidities.     

Postinfectious diffuse proliferative glomerulonephritis and acute renal failure in an HIV patient

Postinfectious proliferative glomerulonephritis may occur in HIV-infected patients, although it is not a common cause of severe acute renal failure in them. We report a woman with HIV infection, who developed hypocomplementemic acute nephritic syndrome 10 days after an upper respiratory infection. Systemic diseases were excluded. The serum creatinine level increased to 6.6 mg/dl. Renal biopsy showed diffuse endocapillary proliferative glomerulonephritis, with mesangial and capillary walls, granular deposits of IgG and C3 by immunofluorescence. She was given corticosteroids with progressive normalization of her renal function. No opportunistic infections have occurred during 1-year follow-up.     

Incidence and risk factors of HCV and HIV infections in a cohort of intravenous drug users in the North and East of France

In order to evaluate the incidence and risk factors of infection by hepatitis C virus (HCV) among injecting drug users (IDUs), we conducted a prospective cohort study of HCV- and human immunodeficiency virus (HIV)-negative IDUs in the North and East of France. A total of 231 HCV and HIV IDUs who had injected drugs at least once in their lifetime were followed up every 3 months over a 12-month period. Serum anti-HCV and anti-HIV were tested at inclusion in the study and at the end of the follow-up. Data on injecting practices were collected at inclusion and at each visit. Of the 231 participants included, 165 (71.4%) underwent a final HCV and HIV serum test. The incidence was nil for HIV infection and 9/100 person-years (95% CI 4.6-13.4) for HCV infection. In a multivariable analysis, we found that syringe and cotton sharing were the only independent predictive factors of HCV seroconversion.     

Evaluating the validity of animal models for research into therapies for immune-based disorders

The last few decades of the 20th century have shown an intensified search for safer and more effective medications against chronic diseases that burden ageing societies of the western world. The impressive development of biotechnological production techniques has greatly facilitated the pharmaceutical development of relatively non-toxic biological molecules. However, despite the huge investments, only a few effective therapies for immune-based diseases have reached the clinic. In this article we use examples from monoclonal antibody trials to discuss the validity and predictive strength of the animal models currently used for the development of effective therapies.     

Two further cases of Ohdo syndrome delineate the phenotypic variability of the condition

Ohdo syndrome (MIM 249620) is a multiple malformation syndrome characterized by blepharophimosis, ptosis, dental hypoplasia, hearing impairment and intellectual disability. A wide range of dysmorphic features and congenital abnormalities have been described in cases reported as Ohdo and Ohdo-like syndromes. We report a further two cases of Ohdo syndrome, one with mild features and the other more severely affected, illustrating the phenotypic variability of the condition. A review of the literature highlights the severe phenotype associated with distinctive facial features, as seen in Case 2 in this report All cases with the severe phenotype have been sporadic. Subtelomeric FISH studies of all chromosome arms on the two cases showed no abnormality. We propose clinical criteria for the diagnosis of Ohdo syndrome and delineate features of the severe phenotype.     

Imipenem resistance in Salmonella enterica serovar Wien related to porin loss and CMY-4 beta-lactamase production

Two multidrug-resistant Salmonella enterica serovar Wien strains (SW468 and SW1107) were isolated in 2001 in Tunis. Both strains produced the beta-lactamases TEM-1, SHV-2a, and CMY-4, whereas strain SW1107 also produced the beta-lactamase CTX-M-3. The imipenem-resistant strain (SW468) was totally devoid of the OmpF-immunorelated porin. Imipenem resistance was shown as being related to porin loss and CMY-4 beta-lactamase production.