T cells or active epstein-barr virus infection in the development of lymphoproliferative disease in human B cell-injected severe combined immunodeficient mice

Background: Severe combined immunodeficient (SCID) mice develop Epstein-Barr virus (EBV) containing human lymphoproliferative disease (LPD) tumors when reconstituted with human peripheral blood leukocytes (PBLs) from EBV-seropositive donors, but LPD tumors do not develop in the presence of immunosuppressive agents, such as cyclosporine A or corticosteroids. Methods: Therefore, LPD development in SCID mice was used as a model to explore the relationship among B cells, T cells, and EBV in vivo. SCID mice were engrafted with PBLs isolated by leukapheresis from a single EBV-seropositive donor. Purified populations of CD3⁺ lymphocytes (T cells) or CD19⁺ lymphocytes (B cells) were isolated and engrafted into SCID mice. Results: SCID mice engrafted with purified CD3⁺ lymphocytes (T cells) or CD19⁺ lymphocytes (B cells) did not develop LPD. In contrast, mice engrafted with purified B cells developed LPD if they were co-engrafted with purified T cells or if they were inoculated with infections EBV. Conclusions: This study confirms the requirement of T cells or active EBV infection in the development of LPD in animals engrafted with B cells latently infected with EBV. A greater understanding of the cellular and viral interactions leading to transformation and malignancy may allow the development of specific interventional therapies for malignancies in the immunosuppressed host. Presented at the 46th Annual Cancer Symposium of The Society of Surgical Oncology, Los Angeles, California, March 18–21, 1993.     

Partial 2-Stage Exchange for Infected Total Hip Arthroplasty: An Updated Report

BackgroundManagement of an infected total hip arthroplasty (THA) is challenging. The eradication of infection as well as complications of component removal must all be considered. This study is an update on previous reports of treating periprosthetic infection of the hip with a partial 2-stage exchange with retention of the femoral component.MethodsA retrospective review of our practice’s arthroplasty registry from 2000 to 2018 revealed 41 hips with 2-year minimum follow-up that were treated with a 2-stage partial exchange for an infected THA. All first-stage procedures allowed an articulating construct with 1 of 3 variations: cemented constrained liner (13 hips), StageOne Hip Cement Spacer Mold (14 hips), or an antibiotic polymethylmethacrylate head molded from a bulb syringe (14 hips). Of 41 cases, 34 were culture positive, with 3 cases having methicillin-resistant Staphylococcus.ResultsMean follow-up was 5.5 years (range, 1.5-18.5 years). The second-stage reimplantation was accomplished in 39 of the 41 hips (95%) at a mean interval of 9.2 weeks (range, 5-9 weeks). Two patients underwent repeat radical debridement with removal of all components before reimplantation for persistent clinical evidence of infection. Thirty-three of the 41 hips (81%) were infection free at most recent follow-up. The mean postoperative Harris hip score at most recent evaluation was 63.6 (range, 24-100).ConclusionEradication of periprosthetic joint infections, while minimizing patient morbidity, continues to be a challenge. Partial 2-stage exchange may be considered in cases where removal of a well-fixed femoral component may result in significant bony destruction.     

Cognitive and functional deficits are associated with white matter abnormalities in two independent cohorts of patients with schizophrenia

European Archives of Psychiatry and Clinical Neuroscience - Significant evidence links white matter (WM) microstructural abnormalities to cognitive impairment in schizophrenia (SZ), but the...     

Serotonin1A receptor deletion does not interact with maternal separation-induced increases in startle reactivity and prepulse inhibition deficits

Rationale  

Early life stress is a risk factor for the development of psychopathology in later life. Consequences of adverse life events, however, may depend on the genetic makeup of an individual. Reduced serotonin_1A receptor function may predispose to the development of anxiety disorders.     

Transverse fractures of the olecranon: a biomechanical comparison of three fixation techniques

Introduction  

The gold standard for treating transverse olecranon fractures is tension band fixation. A problem with this technique is migration of the K-wires leading to premature hardware removal. The aim of this study is to compare stability provided by two new techniques designed to eliminate the problem with backing out of K-wires, with that of the recommended tension band technique, performed with a biomechanical in vitro investigation. Our hypothesis was that the two new techniques would provide at least equal stability as the traditional tension band fixation.     

GABA(A)-benzodiazepine receptor complex sensitivity in 5-HT(1A) receptor knockout mice on a 129/Sv background

Previous studies in 5-HT(1A) receptor knockout (1AKO) mice on a mixed Swiss Websterx129/Sv (SWx129/Sv) and a pure 129/Sv genetic background suggest a differential gamma-aminobutyric acid (GABA(A))-benzodiazepine receptor complex sensitivity in both strains, independent from the anxious phenotype. To further investigate these discrepancies, various GABA(A)-benzodiazepine receptor ligands were tested in different behavioral paradigms in 1AKO and wild type (WT) mice on a 129/Sv background. 1AKO and WT mice responded comparably to alprazolam, flumazenil, alcohol and pentylenetetrazol as measured in the stress-induced hyperthermia paradigm. In addition, sedative-anesthetic effects of pentobarbital measured via the righting reflex were similar and a selected dose of diazepam exerted similar anxiolytic effects in both genotypes in the elevated plus maze. In conclusion, 1AKO mice on a 129/Sv background have undisturbed GABA(A)-benzodiazepine receptor sensitivity in contrast to those described on a mixed Swiss Websterx129/Sv background. The anxious phenotype of 1AKO mice seems to occur independent of the GABA(A)-benzodiazepine receptor complex functioning.     

Overexpression of corticotropin-releasing hormone in transgenic mice and chronic stress-like autonomic and physiological alterations

To gain a greater insight into the relationship between hyperactivity of the corticotropin-releasing hormone (CRH) system and autonomic and physiological changes associated with chronic stress, we developed a transgenic mouse model of central CRH overproduction. The extent of central and peripheral CRH overexpression, and the amount of bioactive CRH in the hypothalamus were determined in two lines of CRH-overexpressing (CRH-OE) mice. Furthermore, 24 h patterns of body temperature, heart rate, and activity were assessed using radiotelemetry, as well as cumulative water and food consumption and body weight gain over a 7-day period. CRH-OE mice showed increased amounts of CRH peptide and mRNA only in the central nervous system. Despite the presence of the same CRH transgene in their genome, only in one of the two established lines of CRH-OE mice (line 2122, but not 2123) was overexpression of CRH associated with increased levels of bioactive CRH in the hypothalamus, increased body temperature and heart rate (predominantly during the light (inactive) phase of the diurnal cycle), decreased heart rate variability during the dark (active) phase, and increased food and water consumption, when compared with littermate wildtype mice. Because line 2122 of the CRH transgenic mice showed chronic stress-like neuroendocrine and autonomic changes, these mice appear to represent a valid animal model for chronic stress and might be valuable in the research on the consequences of CRH excess in situations of chronic stress.