Monoubiquitination and cellular distribution of XIAP in neurons after traumatic brain injury.

XIAP is a member of the inhibitor of apoptosis (IAP) gene family that, in addition to suppressing cell death by inhibition and polyubiquitination of caspases, is involved in an increasing number of signaling cascades. Moreover, the function and regulation of XIAP in the central nervous system (CNS) is poorly understood. In this study, the authors investigated the cell-type expression, the subcellular distribution, ubiquitination of XIAP, and levels of Smac/DIABLO in the normal adult rat brain and in brains subjected to moderate traumatic brain injury (TBI). In the normal brain, XIAP was predominantly expressed in the perinuclear region of neurons. Traumatized brains showed dramatic alterations in cellular and regional expression of XIAP early after injury. Stereologic analyses of the number of XIAP-positive cells within the hippocampus of both hemispheres showed a biphasic response. Immunoprecipitation and immunoblots of extracts derived from different brain regions demonstrated that a single ubiquitin modifies XIAP. Normal cortex contained significantly higher levels of monoubiquitinated XIAP than hippocampus. TBI induced alterations in levels of monoubiquitinated XIAP that correlated with changes in XIAP distribution and immunoreactivity, suggesting that monoubiquitination of XIAP may be a regulator of XIAP location or activity. Similar levels of Smac/DIABLO were present in lysates of normal and traumatized brains. These data demonstrate for the first time a region-specific regulation of XIAP monoubiquitination in the normal adult rat brain, and after TBI, that may be a key event in the regulation of XIAP function contributing to the pathogenesis following injury.     

Home-based primary care: the care of the veteran at home

Home-Based Primary Care is a program designed by the Department of Veteran Affairs (VA) to care for frail, medically complex, elderly veteran patients in their home setting. Unique to the VA, the program has similarities and differences in relation to typical Medicare/Medicaid home health and hospice programs. The VA has demonstrated success in maintaining the patients' independence and quality of life as well as exceptional management of chronic disease and prevention.     

Mutagenicity of zidovudine, lamivudine, and abacavir following in vitro exposure of human lymphoblastoid cells or in utero exposure of CD-1 mice to single agents or drug combinations

Experiments were performed to investigate the impact of zidovudine (AZT), lamivudine (3TC), and abacavir (ABC) on cell survival and mutagenicity in two reporter genes, hypoxanthine-guanine phosphoribosyltransferase (HPRT) and thymidine kinase (TK), using cell cloning assays for assessing the effects of individual drugs/drug combinations in (1) TK6 human lymphoblastoid cells exposed in vitro and (2) splenic lymphocytes from male CD-1 mice exposed transplacentally on days 12-18 of gestation. In TK6 cells, dose-related increases in HPRT and TK mutant frequencies were found following 3 days of exposure to AZT or 3TC alone (33, 100, or 300 microM), or to equimolar amounts of AZT-3TC. Compared with single drug exposures, AZT-3TC coexposures generally yielded enhanced elevations in HPRT and TK mutant frequencies. Mutagenicity experiments with ABC alone, or in combination with AZT-3TC, were complicated by the extreme cytotoxicity of ABC. Exposure of cells either to relatively high levels of AZT-3TC short-term (100 microM, 3 days), or to peak plasma-equivalent levels of AZT-3TC for an extended period (10 microM, 30 days), resulted in similar drug-induced mutagenic responses. Among sets of mice necropsied on days 13, 15, or 21 postpartum, Hprt mutant frequencies in T-cells were significantly elevated in the AZT-only (200 mg/kg bw/day) and AZT-3TC (200 mg AZT + 100 mg 3TC/kg bw/day) groups at 13 days of age. These results suggest that the mutagenicity by these nucleoside analogs is driven by cumulative dose, and raises the question of whether AZT-3TC has greater mutagenic effects than AZT alone in perinatally exposed children.     

Passing through: meanings of survivorship and support among Filipinas with breast cancer

Breast cancer among Filipinas in the United States is a major but largely neglected cancer disparity. In 2004, a community- university partnership resulted in the first Filipina breast cancer support group in the San Francisco Bay Area. Building on this partnership, we explored the social and cultural contexts of Filipinas' experiences with breast cancer to inform development of culturally appropriate and sustainable support services and outreach. We utilized multiple qualitative methods (participant observation, individual and small group in-depth qualitative interviews) to identify meanings of survivorship and support. Interviews and observations revealed the influences of social context and immigration experiences on women's understandings of cancer, what "surviving" cancer means, and what it means to take care of someone with breast cancer (or be taken care of). Our findings highlight the importance of a transnational perspective for the study of immigrant women's experiences of cancer and survivorship.     

Radiofrequency by open surgical approach in the treatment of hepatic tumours: early experience with 14 cases

The aim of the study was the evaluation of radiofrequency in the treatment of hepatic tumours during laparotomy performed for hepatic tumours. The initial experience with 14 patients operated for hepatic tumours (5 primary and 9 metastatic) is presented. The paper also presents the technique concerning the intensity and duration of the power applied, the association with the surgical resection, the immediate postoperative evolution and the dynamics of the hepatic enzymes as well as the postoperative results of ultrasound and CT examinations performed within the first 6 weeks. The indications of RF during laparotomy and the place of RF ablation in the treatment of liver tumours in comparison with other ablation techniques are discussed     

Nosocomial infections among pediatric hematology/oncology patients: results of a prospective incidence study

BACKGROUND: Nosocomial infections (NI) are an important clinical complication in adult and children patients at the different hospital wards. NI cause considerable morbidity and mortality and are associated with prolonged hospital stay and increased health care costs. OBJECTIVE: The objective of this study was to describe the incidence of NI in pediatric patients with neoplastic disease as a first step toward improving infection control policies. METHODS: A prospective surveillance study from March through May 2001 was performed in the pediatric hematology/oncology unit at the University Hospital in Barcelona. The Centers for Disease Control and Prevention criteria were used as standard definition for NI. NI rates were calculated as a density incidence rate (per 100 patient-days). RESULTS: Fifty-one patients were admitted during the study period. Twelve patients had a total of 18 NI. The incidence of NI was 1.77 per 100 patient-days. Patients with acute lymphoblastic leukemia had the highest NI rate (2.71 per 100 patient-days). The most frequent episodes of NI were bacteremia (55.5%) and fever of unknown origin (16.6%). The most frequently isolated microorganisms were gram-positive bacteria (78.6%). Coagulase-negative Staphylococci were the most common isolates in bacteremias (70%). The extrinsic risk factors related with the highest incidence rates of NI per 100 patient-days were central venous catheterization (1.7 infections) and parenteral nutrition (3.2 infections). CONCLUSIONS: Extrinsic risk factors associated with NI have been identified in this high-risk population. These findings suggest the need to evaluate the infection control measures to reduce the morbidity and mortality in a hematology/oncology unit.     

Compound heterozygosity of HLA‐DRB3*01:01 and HLA‐DRB4*01:01 as a potential predictor of fetal neonatal alloimmune thrombocytopenia

BACKGROUND: Fetal neonatal alloimmune thrombocytopenia (FNAIT) is a life‐threatening bleeding disorder in the fetus or neonate caused by maternal alloantibodies directed against fetal platelet (PLT) antigens inherited from the father. The immune‐dominant antigen leading to severe FNAIT is the human PLT antigen (HPA)‐1, whose polymorphism constitutes an epitope for human leukocyte antigens (HLAs), usually DRB3*0101 leading to an immune response. STUDY DESIGN AND METHODS: In this study our aims were to find whether other allele variants of the β subunit of the HLA‐DR family specifically focused on the HLA residues that bind Position 33 of the HPA‐1 integrin contribute to FNAIT development and affect response to treatment and whether coexistence of both anti‐HPA‐1a and anti‐HLA Class I specific against the father's antigens leads to a more severe thrombocytopenia in the newborn. We examine the genotype of 23 mothers to newborns with FNAIT compared to a control group. RESULTS: Our results suggested that, when HPA‐1 incompatibility with the husband is found, the presence of two HLA alleles (DRB3*01:01 and DRB4*01:01) in the mother increases the risk and severity of FNAIT and reduces the success of a preventive immunoglobulin G treatment. We provide a structural model for the molecular basis of the rational effects of the different HLA alleles. In addition, we found that the presence of both anti‐HPA‐1 and anti‐HLAs did not aggravate FNAIT in comparison to mothers harboring only anti‐HPA‐1. CONCLUSION: Overall, we suggest that a specific genotyping of the mother in relation to HLA‐DRB as well as HPA‐1 can serve as an antenatal diagnostic tool, particularly in siblings of women who gave birth to neonates with FNAIT.     

A topographic measurement of brain pH

The ability of neutral red to serve as an internal pH indicator in biological systems was tested in the rat brain after parenteral administration of the dye. The injected dye is avidly taken up by the brain cells and is distributed mainly in intracellular organelles. The ratio of optical signals recorded from the frozen brain at 445 and 530 nm and compared with calibration curves provides pH values. Color transition of neutral red ranges from 6.0 to 8.0 pH units. Topographic application of this method is particulary useful in studying local pH changes in brains with developing ischemic foci.     

Axenfeld–Rieger ocular anomaly and retinoblastoma caused by constitutional chromosome 13q deletion

Axenfeld–Rieger (AR) ocular anomaly might be due to deletions of different chromosomes. No association between AR, mental retardation, and retinoblastoma has been described. We report a 2‐month‐old female with general development delay and dysmorphic features. AR anomaly was detected, and a retinoblastoma (RB) was diagnosed in a very early stage. De novo 13q deletion was identified. Systemic chemotherapy, focal cryotherapy, transpupillary thermotherapy, brachytherapy, and intra‐arterial chemotherapy were needed to control the RB. This is the first report of an association of AR, 13q deletion, and retinoblastoma, to be disclosed in patients born with such ocular and dysmorphic features. Pediatr Blood Cancer 2010;54:480–482. © 2009 Wiley‐Liss, Inc.