Choreito formula for BK virus-associated hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation.

Therapy for BK virus (BKV)-associated hemorrhagic cystitis (BKV-HC) is limited after hematopoietic stem cell transplantation (HSCT). We examined whether choreito, a formula from Japanese traditional Kampo medicine, is effective for treating BKV-HC. Among children who underwent allogeneic HSCT between October 2006 and March 2014, 14 were diagnosed with BKV-HC (median, 36 days; range, 14 to 330 days) after HSCT, and 6 consecutive children received pharmaceutical-grade choreito extract granules. The hematuria grade before treatment was significantly higher in the choreito group than in the nonchoreito group (P = .018). The duration from therapy to complete resolution was significantly shorter in the choreito group (median, 9 days; range, 4 to 17 days) than in the nonchoreito group (median, 17 days; range, 15 to 66 days; P = .037). In 11 children with macroscopic hematuria, the duration from treatment to resolution of macroscopic hematuria was significantly shorter in the choreito group than in the nonchoreito group (median, 2 days versus 11 days; P = .0043). The BKV load in urine was significantly decreased 1 month after choreito administration. No adverse effects related to choreito administration were observed. Choreito may be a safe and considerably promising therapy for the hemostasis of BKV-HC after HSCT.

Production of human papillomavirus type 16 virus-like particles in transgenic plants.

Cervical cancer is linked to infection with human papillomaviruses (HPV) and is the third most common cancer among women worldwide. There is a strong demand for the development of an HPV preventive vaccine. Transgenic plants expressing the HPV major capsid protein L1 could be a system to produce virus-like particles for prophylactic vaccination or could even be used as edible vaccines to induce an L1-specific prophylactic immune response. Here, we describe the generation of transgenic tobacco and potato plants carrying the HPV type 16 major structural gene L1 under the control of the cauliflower mosaic virus 35S promoter. All attempts to express either the original, unmodified L1 gene or an L1 gene with a codon usage optimized for expression in plants failed. Surprisingly, small amounts of the protein were detected using an L1 gene optimized for expression in human cells. However, Northern blot analysis revealed that most of the L1 transcripts were degraded. Introduction of the translational enhancer Omega derived from the tobacco mosaic virus strongly increased transcript stability and resulted in accumulation of L1 protein to approximately 0.5 to 0.2% of total soluble protein in transgenic tobacco and potato plants, respectively. The plant-derived L1 protein displayed conformation-specific epitopes and assembled into virus-like particles. Furthermore, we did not find any indications of protein modification of the L1 protein produced in plants. Plant-derived L1 was as immunogenic as L1 expressed in baculovirus-infected insect cells. Feeding of tubers from transgenic potatoes to mice induced an anti-L1 antibody response in 3 out of 24 mice, although this response was only transient in two of the mice. Our data, however, indicate that an anti-L1 response was primed in about half of the 24 animals.

Life stress and cervical squamous intraepithelial lesions in women with human papillomavirus and human immunodeficiency virus.

OBJECTIVE: Human immunodeficiency virus (HIV)-infected women are at risk for cervical intraepithelial neoplasia (CIN) and cancer due to impaired immunosurveillance over human papillomavirus (HPV) infection. Life stress has been implicated in immune decrements in HIV-infected individuals and therefore may contribute to CIN progression over time. The purpose of this study was to determine whether life stress was associated with progression and/or persistence of squamous intraepithelial lesions (SIL), the cytologic diagnosis conferred by Papanicolaou smear, after 1-year follow-up among women co-infected with HIV and HPV. METHOD: Thirty-two HIV-infected African-American and Caribbean-American women underwent a psychosocial interview, blood draw, colposcopy, and HPV cervical swab at study entry. Using medical chart review, we then abstracted SIL diagnoses at study entry and after 1-year follow-up. RESULTS: Hierarchical logistic regression analysis revealed that higher life stress increased the odds of developing progressive/persistent SIL over 1 year by approximately seven-fold after covarying relevant biological and behavioral control variables. CONCLUSIONS: These findings suggest that life stress may constitute an independent risk factor for SIL progression and/or persistence in HIV-infected women. Stress management interventions may decrease risk for SIL progression/persistence in women living with HIV.

Stressful events, pessimism, natural killer cell cytotoxicity, and cytotoxic/suppressor T cells in HIV+ black women at risk for cervical cancer.

OBJECTIVE: This study examines whether stressful negative life events and pessimism were associated with lower natural killer cell cytotoxicity (NKCC) and T cytotoxic/suppressor cell (CD8+CD3+) percentage in black women co-infected with human immunodeficiency virus Type 1 (HIV-1) and human papillomavirus (HPV), a viral initiator of cervical cancer. METHOD: Psychosocial interviews, immunological evaluations, and cervical swabs for HPV detection and subtyping were conducted on 36 HIV+ African-American, Haitian, and Caribbean women. RESULTS: Greater pessimism was related to lower NKCC and cytotoxic/suppressor cells after controlling for presence/absence of HPV Types 16 or 18, behavioral/lifestyle factors, and subjective impact of negative life events. CONCLUSIONS: A pessimistic attitude may be associated with immune decrements, and possibly poorer control over HPV infection and increased risk for future promotion of cervical dysplasia to invasive cervical cancer in HIV+ minority women co-infected with HPV.

Neuroimmunopathogenesis of ts1 MoMuLV viral infection.

Newborn mice infected with ts1, a mutant of the Moloney murine leukemia virus, develop neuroimmunodegeneration with death and damage of thymocytes, astrocytes, and motor neurons by 24-38 days. T cells, B cells, and astrocytes, but not neurons, are infected by the virus. Primary splenocytes and thymocytes isolated from age-matched infected or control mice, when incubated in serum-deficient media containing phytohemagglutinin-L, either homotypically aggregate and survive or swell, expose their inner membrane phospholipids, and then shrink as they fragment their nuclei and excrete DNA-containing hypoploid minicells. In our present studies, the rates of these apoptotic changes were greatly increased in the infected cells. This thymocyte death was ameliorated in vitro by addition of Th2 cytokines, but not by Th1 cytokines, or by redox agents. In contrast, death of splenocytes, which were already mitogenically activated in vivo by the virus, was prevented by Th1 and Th2 cytokines plus redox support. In vivo, this ts1-induced neuroimmunodegenerative syndrome could be completely prevented by the immunomodulator polyinosine-cytosine and partially prevented by cytokines or redox modifiers. Viral titer primarily in the brain was also diminished by polyinosine-cytosine therapy. These observations indicate that the cell death in T cells and neurons in these ts1-infected neonatal mice can be prevented in vitro and in vivo by appropriate upregulation of the immune system.

Benign and malignant disease caused by EBV.

Epstein-Barr virus (EBV) causes infectious mononucleosis as a primary disease. The virus infects more than 90% of the average population and persists lifelong in peripheral B-lymphocytes. The virus is produced in the parotid gland and spread via the oral route. Serology suggests that the Epstein-Barr virus might be involved in the causation of two neoplastic diseases of humans: African Burkitt's lymphoma and nasopharyngeal carcinoma. Whereas the development of the lymphoma has an even better linkage with chromosomal rearrangements, nasopharyngeal carcinoma shows a unique association with Epstein-Barr virus. Environmental factors, including traditional Chinese medicine, may be responsible for the enhanced risk of nasopharyngeal carcinoma in certain, predominantly Chinese, populations of southern Asia. Possible mechanisms leading to the establishment of the neoplastic manifestations will be discussed.