Alcohol and other drugs: an assessment of testing and clinical practices in U.S. trauma centers

The PsaC protein binds two 4Fe-4S centers, FA and FB, in the photosystem I (PSI) protein complex. In the T398 strain of Anabaena variabilis ATCC 29413, the psaC gene encoding this protein has been insertionally inactivated by the introduction of a neomycin resistance gene cartridge in the coding region. Photosystem I complex was purified through native gel electrophoresis of beta-dodecyl maltoside solubilized thylakoid membranes from wild-type and T398 strains of Anabaena 29413. The PSI complex from T398 strain retained functionally active P700, the reaction center chlorophylls. Interestingly, purified PSI complex from T398 cells lacked the PsaD, PsaE, and PsaL polypeptides. Western analysis with polyclonal antibodies raised against these proteins indicated that the two stromal exposed polypeptides, PsaD and PsaE, are absent in isolated thylakoid membranes from T398 cells. The PsaL polypeptide could be detected at a level comparable to that in wild-type thylakoid membranes, although it is absent in the PSI preparation from the mutant. These observations suggest that the PsaC protein is essential for the stable association of PsaD and PsaE, two hydrophilic, extrinsic polypeptides. Moreover, PsaL, a hydrophobic protein is loosely associated with PSI and is lost during the isolation of the PSI complex.     

Neuroendocrine differentiation is an independent prognostic factor in chemotherapy-treated nonsmall cell lung carcinoma

BACKGROUND: Neuroendocrine differentiation can be identified in 10-30% of patients with nonsmall cell lung carcinoma (NSCLC) by immunohistochemical or electron microscopic techniques. However, its clinical significance is not well established. METHODS: Tumors from 107 patients with Stage IIIA, IIIB, and IV NSCLC treated with cisplatin/etoposide with or without hydrazine in the North Central Cancer Treatment Group and Mayo Clinic protocols were analyzed immunohistochemically with antibodies to chromogranin A (CGA), Leu 7 (CD 57), and synaptophysin (SY). These results were compared with clinical outcomes. RESULTS: Keratin AE1/AE3, used as a control, was positive in 99.1% of cases; 34.6% had positive staining for at least 1 neuroendocrine marker, and 11.3% had positive staining for 2 or more markers. CGA was positive in 4.7%, Leu 7 in 18.7%, and SY in 24.3% of cases. A significant increase in survival was seen in patients with tumors expressing any one neuroendocrine marker or any combination of neuroendocrine markers (P < or = 0.01). There was no correlation between the presence of neuroendocrine differentiation and either response to chemotherapy or time to disease progression (P > 0.3), nor was there any correlation between chemotherapy response, time to progression, or survival with staining intensity or percent of cells positive per case. CONCLUSIONS: Neuroendocrine differentiation may be of prognostic significance in patients with advanced stage NSCLC treated with chemotherapy.     

Effects of adenosine, ATP, and UTP on chloride secretion by epithelia explanted from fetal rat lung

To determine the role of intensive chemotherapy and allogeneic bone marrow transplantation (BMT) in treatment of refractory anemia with excess of blasts (RAEB) or RAEB-t (in transformation), the outcome of 37 consecutive children, 12 with RAEB and 25 with RAEB-t, diagnosed between 1985 and 1995 was analyzed. Fourteen patients received intensive chemotherapy according to the AML-BFM protocols 83, 87, or 93 (group 1). Seven patients were treated less intensively with the 6-week consolidation phase as induction (group 2). Allogeneic BMT was performed in 10 children of group 1 and 2 after, and in eight (group 3) without prior chemotherapy. Eight children received minimal or no chemotherapy (group 4). Of 21 children (groups 1 and 2) 17 (81%) achieved complete or partial remission after chemotherapy, 12 of them (10 of group 1) remained in remission, eight after BMT. Five-year survival in 29 children treated intensively (groups 1-3) was 46%, SE 12%. Two of the other eight children (group 4) remained alive, one after spontaneous remission. Outcome after BMT was related to the blast count in the bone marrow prior to BMT. None of 10 children (including two with minimal or no chemotherapy) with < or = 12% blasts before BMT relapsed, in contrast to five of eight patients with a higher blast count (P log rank 0.02). We conclude that a substantial number of children with RAEB or RAEB-t can achieve remission with intensive AML-specific chemotherapy. In patients responding to intensive chemotherapy an increase in long-term survival after allogeneic BMT can be expected.     

Spontaneous loss of viral episomes accompanying Epstein-Barr virus reactivation in a Burkitt's lymphoma cell line

Life-long viral persistence is a hallmark of human herpesvirus infection. In the Epstein-Barr virus (EBV)-positive Burkitt's lymphoma (BL) cell line, Mutu, spontaneous loss of all viral episomes accompanied productive viral DNA replication. The molecular configuration of intracellular EBV DNA evolved from monoclonal episomes in cells retaining the original tumor phenotype to predominantly replicating linear DNA and, subsequently, only integrated forms in BL cells that had acquired the lymphoblastoid cell phenotype. Transient appearance of deleted, rearranged WZhet EBV DNA capable of disrupting viral latency, along with the integration of viral DNA into human chromosomes, indicates a genetic instability in the host cell which, if duplicated in vivo, may affect configuration and persistence of the viral genome in expanding malignant cell clones.     

The clinical relevance of the Waterlow pressure sore risk scale in the ICU

OBJECTIVE: To evaluate whether the Waterlow pressure sore risk (PSR) scale has prognostic significance for intensive care patients. DESIGN: A prospective study. SETTING: The surgical intensive care unit (ICU) of the University Hospital Rotterdam. PATIENTS: Data were evaluated from 594 patients who had been admitted to the ICU during the year 1994. METHODS AND RESULTS: Each patient was assessed daily with respect to their Waterlow PSR score and the development of pressure sores in the sacral region. Actuarial statistical methods were used to analyse the predictive value of the risk score. When a patient had a Waterlow PSR score > 25 on admission, the risk of developing a pressure sore was significantly increased compared to patients with a PSR score < 25. After admission, the daily Waterlow PSR scores obtained were significantly associated with the risk of developing a pressure sore. For each additional point this risk increased by 23% (95% confidence interval 17 to 28%). CONCLUSIONS: The Waterlow PSR scale provides the medical and nursing staff at an early stage with reliable information about the risk patients have in developing a pressure sore.     

A review of new oncotropic tracers for PET imaging

We have developed three biochemical probes to determine if they are sensitive probes of early biochemical change in a tumor. All three probes appear to have the appropriate properties for in vivo imaging, but must now be evaluated as probes for the sensitive detection of changes in early malignant disease.     

The role of glycoproteins gC, gE, gI, and gG in the induction of cell-mediated immune responses to bovine herpesvirus 1

Mutant viruses with deletions in genes encoding non-essential glycoproteins are considered as promising bovine herpesvirus 1 (BHV1) vaccine candidates. The present study compared the influence of various gene deletions (gC, gE, gI, gG) on the induction of cell-mediated immune responses against the virus. The highest BHV1 specific lymphoproliferative response was observed in the group of calves inoculated with the gC- mutant. However, in all groups of inoculated calves, limiting dilution analysis showed marked individual variability in the number of BHV1 specific T lymphocytes that were stimulated. The same animals were then challenged with wild-type BHV1. In these animals, limiting dilution analysis did not reveal gE, gI nor gG as a major T lymphocyte antigen. However, further analysis suggested the T cell antigenicity of gE in a low number of BHV1 hyperimmunized calves. Stimulation of MHC unrestricted cytotoxicity was also evaluated after inoculation with the various deletion mutants. Cytotoxicity in gC- inoculated calves was as high as in BHV1 inoculated calves. In conclusion, among the BHV1 deletion mutants that were tested, the gC- mutant stimulated the best cell-mediated immune responses.