Poxvirus-based vaccine therapy for patients with advanced pancreatic cancer

Purpose  

An open-label Phase 1 study of recombinant prime-boost poxviruses targeting CEA and MUC-1 in patients with advanced pancreatic cancer was conducted to determine safety, tolerability and obtain preliminary data on immune response and survival.     

Dynamic MRI with projection reconstruction and KWIC processing for simultaneous high spatial and temporal resolution.

A method for dynamic imaging in MRI is presented that enables the acquisition of a series of images with both high temporal and high spatial resolution. The technique, which is based on the projection reconstruction (PR) imaging scheme, utilizes distinct data acquisition and reconstruction strategies to achieve this simultaneous capability. First, during acquisition, data are collected in multiple undersampled passes, with the view angles interleaved in such a way that those of subsequent passes bisect the views of earlier ones. During reconstruction, these views are weighted according to a previously described k-space weighted image contrast (KWIC) technique that enables the manipulation of image contrast by selective filtering. Unlike conventional undersampled PR methods, the proposed dynamic KWIC technique does not suffer from low image SNR or image degradation due to streaking artifacts. The effectiveness of dynamic KWIC is demonstrated in both simulations and in vivo, high-resolution, contrast-enhanced imaging of breast lesions.     

Polymorphism p53 codon-72 and invasive cervical cancer: a meta-analysis.

OBJECTIVES: Although some studies have reported that the arginine isoform on codon 72 of p53 increases the susceptibility to invasive cervical cancer, such data remain controversial. The objective of this study was to quantitatively summarize the evidence for such a relationship. METHODS: Our data sources consisted of a MEDLINE search of the literature published before December 2002, bibliography review, and expert consultation. Thirty-seven studies met the inclusion criteria. Information on sample size, study design, Hardy-Weinberg equilibrium, and method of genotype determination was abstracted by two reviewers using a standardized protocol. The overall odds ratio (OR) of the p53 gene on invasive cervical cancer was estimated using the Mantel-Haenzel method. RESULTS: The overall OR (95% confidence interval) for cervical cancer among those with the homozygous mutant (Arg/Arg) was 1.2 (1.1-1.3, P=0.001) compared with those with the heterozygous mutant (Arg/Pro). By a cellular type of cervical cancer, the overall OR among those with Arg/Arg was statistically significant in adenocarcinomas (1.7, 1.1-2.6, P=0.024), but not in squamous cell carcinomas (1.1, 0.9-1.2, P=0.960), compared with Pro/Pro. Compared with Arg/Pro, the OR among those with Arg/Arg was statistically significant in HPV types 16 (1,5, 1.2-2.0, P=0.002). CONCLUSIONS: Overall, the p53 gene was associated with increased risk for invasive cervical cancer. However, the risk varied by country, cellular, and HPV type.     

Comparison of the biomechanical effect of posterior condylar offset and kinematics between posterior cruciate-retaining and posterior-stabilized total knee arthroplasty

Background

The effect of the changes in the femoral posterior condylar offset (PCO) on anterior–posterior (AP) translation and internal–external (IE) rotation in cruciate-retaining (CR) and posterior-stabilized (PS) total knee arthroplasty (TKA) remains unknown. The purpose of this study was to compare the kinematics in CR and PS TKA with respect to the difference in prosthetic design and PCO change through a computational simulation.

Nonspecific induction of immunoglobulin M antibodies to periodontal disease-associated microorganisms after polyclonal human B-lymphocyte activation by Fusobacterium nucleatum.

The production of antibodies to oral bacteria was determined in lymphocyte cultures stimulated with sonicated Fusobacterium nucleatum, a potent inducer of polyclonal B-cell activation. After 9 days the cultures were examined by a microenzyme-linked immunosorbent assay for immunoglobulin M (IgM) antibodies to F. nucleatum, Bacteroides gingivalis, Actinomyces viscosus, and Streptococcus sanguis. Antibodies to these four bacteria were detected in cultures stimulated with polyclonal B-cell activation-inducing concentrations of F. nucleatum. However, significant concentrations of antibodies to F. nucleatum, but not to the other three microorganisms, were produced in cultures that received suboptimal polyclonal B-cell activation-inducing doses of F. nucleatum. Absorption studies indicated the specificity of the antibodies to each of the bacteria tested. IgM antibody production induced by F. nucleatum was enhanced by the addition of T cells. The production of IgM antibodies to the bacteria was reproducible in cultures from a single person tested on 3 consecutive days. The concentration of antibodies in replicate cultures, however, fluctuated greatly. To obtain consistent responses on successive days, multiple replicate cultures were required. These results suggest that F. nucleatum, which is frequently present in subgingival plaque, could induce the production of antibodies not only to F. nucleatum, but also to other microorganisms associated with periodontal diseases.     

Malignant rhabdoid tumor of the kidney--a case report.

Malignant rhabdoid tumor is a distinct renal tumor in children. It had been regarded as a rhabdomyosarcomatoid variant of Wilms' tumor, but it is now thought as a separate entity. We report a case of malignant rhabdoid tumor of the kidney in a 26-month-old girl who presented with a left abdominal mass. Grossly, a large mass in the lower pole of the left kidney was well encapsulated and measured 4 x 4 x 3.5cm. On cross section, it was soft and yellowish white and showed multifocal necroses. The mass was mainly located in the medial medullary portion and compressed the renal pelvis laterally. Microscopically, the tumor masses were hypercellular and anaplastic without definite blastematous elements. In larger portion, the tumor cells had abundant eosinophilic cytoplasm and hyaline globules. In addition to the classic "rhabdoid" feature, alveolar, sclerosing, and lymphomatous patterns were seen. Ultrastructurally, tumor cells with abundant cytoplasm contained tangles of intermediate filament corresponding to vimentin in immunostaining.     

Inhibition of interleukin-8 expression by dexamethasone in human cultured airway epithelial cells.

Interleukin-8 (IL-8) is a neutrophil chemotactic factor expressed in many cell types, including human airway epithelial cells (HAEC). Inhaled corticosteroids are now used increasingly early in the treatment of airway inflammation such as in asthma, and directly interact with HAEC at relatively high concentrations. We have investigated the effect of dexamethasone on IL-8 expression in primary cultured HAEC obtained from transplantation donors. Northern blot analysis was used to measure IL-8 mRNA levels in HAEC, and radioimmunoassay was used to measure IL-8 protein in culture supernatant fluids. We demonstrated that IL-8 was expressed by primary cultured HAEC and that this was enhanced by IL-1 beta and tumour necrosis factor-alpha stimulation, but not by IL-6 or lipopolysaccharide. Dexamethasone suppressed IL-8 mRNA expression and protein synthesis dose-dependently in both resting and stimulated HAEC. The half-life of IL-8 mRNA determined in the presence of actinomycin D was less than 1 hr, and dexamethasone preincubation had no effect on mRNA stability. These results support the view that HAEC may play an important role in the pathogenesis of airway inflammatory diseases, and that glucocorticosteroids may exert their anti-inflammatory effects by blocking IL-8 gene expression and generation in these cells.     

Spontaneous disruption of mycotic aneurysm involving innominate artery

We report a case of ruptured mycotic aneurysm involving innominate artery requiring an urgent surgical treatment. A 62-yr-old woman presented with fever and dyspnea. Previously, she was diagnosed with colon cancer and received right hemicolectomy and one cycle of adjuvant chemotherapy. On echocardiogram, pericardial effusion was noted and emergency pericardiocentesis was performed. CT scan revealed aortic aneurysm involving ascending aorta and innominate artery, and thrombi surrounding those structures. Patch repair of the defect in the ascending aorta and ringed Goretex graft to bypass the innominate and ascending aorta were performed. We believe that this is the first case of ruptured mycotic aneurysm involving innominate artery.     

Identification of vaccine candidate peptides in the NcSRS2 surface protein of Neospora caninum by using CD4+ cytotoxic T lymphocytes and gamma interferon-secreting T lymphocytes of infected holstein cattle

Previously, our laboratory showed that Holstein cattle experimentally infected with Neospora caninum develop parasite-specific CD4+ cytotoxic T lymphocytes (CTL) that lyse infected, autologous target cells through a perforin-granzyme pathway. To identify specific parasite antigens inducing bovine CTL and helper T-lymphocyte responses for vaccine development against bovine neosporosis, the tachyzoite major surface proteins NcSAG1 and NcSRS2 were targeted. In whole tachyzoite antigen-expanded bovine T-lymphocyte lines, recombinant NcSRS2 induced potent memory CD4+- and CD8+-T-lymphocyte activation, as indicated by proliferation and gamma interferon (IFN-gamma) secretion, while recombinant NcSAG1 induced a minimal memory response. Subsequently, T-lymphocyte epitope-bearing peptides of NcSRS2 were mapped by using overlapping peptides covering the entire NcSRS2 sequence. Four experimentally infected cattle with six different major histocompatibility complex (MHC) class II haplotypes were the source of immune cells used to identify NcSRS2 peptides presented by Holstein MHC haplotypes. NcSRS2 peptides were mapped by using IFN-gamma secretion by rNcSRS2-stimulated, short-term T-lymphocyte cell lines, IFN-gamma enzyme-linked immunospot (ELISPOT) assay with peripheral blood mononuclear cells, and 51Cr release cytotoxicity assay of rNcSRS2-stimulated effector cells. Four N. caninum-infected Holstein cattle developed NcSRS2 peptide-specific T lymphocytes detected ex vivo in peripheral blood by IFN-gamma ELISPOT and in vitro by measuring T-lymphocyte IFN-gamma production and cytotoxicity. An immunodominant region of NcSRS2 spanning amino acids 133 to 155 was recognized by CD4+ T lymphocytes from the four cattle. These findings support investigation of subunit N. caninum vaccines incorporating NcSRS2 gene sequences or peptides for induction of NcSRS2 peptide-specific CTL and IFN-gamma-secreting T lymphocytes in cattle with varied MHC genotypes.     

Clonorchis sinensis: molecular cloning and localization of myosin regulatory light chain

One cDNA clone was purified from an adult Clonorchis sinensis cDNA library, and its deduced polypeptide sequence was found to be homologous with myosin regulatory light chain (MRLC) of invertebrates and vertebrates. Two amino-acid residues, Thr and Ser, were conserved at the phosphorylation sites that regulate the function of MRLCs. Recombinant C. sinensis MRLC (rCsMRLC) protein was produced and purified from Escherichia coli, and mouse anti-CsMRLC immune sera recognized a protein of molecular weight 24 kDa from a soluble protein preparation of C. sinensis. The CsMRLC protein was immunohistochemically localized to the muscle fibers of the subtegumental muscle layer and to the muscles of oral and ventral suckers. However, the rCsMRLC protein proved to be less useful antigen for the serodiagnosis of human clonorchiasis.The nucleotide sequence reported herein was submitted to GenBank and assigned accession number AY519356.