Amoxicillin-Induced Eosinophilic Pneumonia with Granulomatous Reaction: Discrepancy between Drug-Induced Lymphocyte Stimulation Test Findings and the Provocation Drug Test

<p/> <p>A 59-year-old man was admitted to the hospital with pulmonary infiltration, fever, erythema, and eosinophilia. Two weeks before admission, he received amoxicillin, acetaminophen, and shoseiryu-to (a Japanese herbal medicine) for a common cold. Bronchoalveolar lavage was performed, and an increased number of eosinophils was recovered. Transbronchial biopsy specimens showed granuloma and interstitial thickening with eosinophils and lymphocytes. Drug-induced eosinophilic pneumonia was suspected, so all drugs were discontinued. The symptoms and infiltration shadow disappeared. A drug-induced lymphocyte stimulation test (DLST) was positive for acetaminophen but not for amoxicillin. In contrast to the DLST, a provocation test revealed that amoxicillin induced the drug allergy. A very striking observation was the coexistence of pulmonary eosinophilia and granulomatous lung infiltrations. In addition, there was a discrepancy between the DLST and provocation test findings. To our knowledge, there is no previous report of drug-induced eosinophilic pneumonia with a granulomatous reaction.</p

A cell factory of Bacillus subtilis engineered for the simple bioconversion of myo-inositol to scyllo-inositol, a potential therapeutic agent for Alzheimer's disease

<p>Abstract</p> <p>Background</p> <p>A stereoisomer of inositol, <it>scyllo</it>-inositol, is known as a promising therapeutic agent for Alzheimer's disease, since it prevents the accumulation of beta-amyloid deposits, a hallmark of the disease. However, this compound is relatively rare in nature, whereas another stereoisomer of inositol, <it>myo</it>-inositol, is abundantly available.</p> <p>Results</p> <p><it>Bacillus subtilis </it>possesses a unique inositol metabolism involving both stereoisomers. We manipulated the inositol metabolism in <it>B. subtilis </it>to permit the possible bioconversion from <it>myo</it>-inositol to <it>scyllo</it>-inositol. Within 48 h of cultivation, the engineered strain was able to convert almost half of 10 g/L <it>myo</it>-inositol to <it>scyllo</it>-inositol that accumulated in the culture medium.</p> <p>Conclusions</p> <p>The engineered <it>B. subtilis </it>serves as a prototype of cell factory enabling a novel and inexpensive supply of <it>scyllo</it>-inositol.</p

Transcriptional activation of a hybrid promoter composed of cytomegalovirus enhancer and β-actin/β-globin gene in glomerular epithelial cells in vivo

Transcriptional activation of a hybrid promoter composed of cytomegalovirus enhancer and β-actin/β-globin gene in glomerular epithelial cells in vivo. The aim of this study was to seek a promoter, transactivated selectively in renal cells in vivo by using transgenic (tg) mouse technology. We generated two kinds of tg mouse lines carrying a green fluorescence protein (GFP) cDNA driven either by cytomegalovirus enhancer and β-actin/β-globin promoter (CX-GFP) or by elongation factor la promoter (EF-GFP), and investigated the expression of GFP in the kidney. Microscopic examination of the renal tissues in CX-GFP-tg mice revealed that GFP was expressed only in glomeruli, mainly epithelial cells, but not in tubules, arteries and interstitium. Moreover, in situ hybridization demonstrated that GFP mRNA expression was localized in the glomerular cells. In contrast, GFP was not detectable in the kidney in any of the lines of EF-GFP-tg mouse. To exclude the possible involvement of the GFP cDNA as an enhancer, we constructed tg mice carrying the CX promoter driving a human CD4 cDNA. It was confirmed that the expression patterns of human CD4 in the kidney were quite similar to those of GFP in the kidney of CX-GFP-tg mice. These results strongly suggest that CX promoter could be transactivated in glomerular epithelial cells in vivo

Gene expression profile of renal proximal tubules regulated by proteinuria

Gene expression profile of renal proximal tubules regulated by proteinuria.BackgroundProximal tubules activated by reabsorption of protein are thought to play significant roles in the progression of kidney diseases. Thus, identification of genes related to proteinuria should provide insights into the pathological process of tubulointerstitial fibrosis.MethodGene expression profiles were constructed by means of direct sequencing procedures to identify genes induced in the mouse kidney proximal tubules (PT) exposed to proteinuria.ResultsBy comparing the gene expression of control PT to that of disease model PT, the abundantly expressed genes in control PT were down-regulated presumably because of potentially toxic effects of proteinuria. From the more than 1000 up-regulated genes, an immunity related gene, thymic shared antigen-1 (TSA-1), and a novel gene, GS188, were selected for further characterization. The increased expression of TSA-1, a member of the Ly-6 family, and of GS188 in response to proteinuria was confirmed by Northern analysis, immunohistochemistry, in situ hybridization and laser microdissection along with real-time PCR analysis. Full length cloning of GS188 identified it as a family member of LR8 that was reported to express predominantly in fibroblasts.ConclusionsThe gene expression profiles showed that the expression patterns in PT were changed dramatically by proteinuria. The profiles include novel genes that should be further characterized to aid the understanding of the pathophysiology of progressive kidney diseases

The Function of β2-glycoprotein I in Angiogenesis and Its in Vivo Distribution in Tumor Xenografts

Intact β2-glycoprotein I (iβ2GPI) is a glycoprotein that regulates coagulation and fibrinolysis. Nicked β2GPI (nβ2GPI) possesses an angiogenic property at a relatively low concentration, and an antiangiogenic property at a high concentration. Here we investigated the functions of βi 2GPI and nβ2GPI in vascular endothelial growth factor (VEGF)-A-induced endothelial cell proliferation and tube formation. We used noninvasive PET imaging to analyze the in vivo distribution of intravenously injected β2GPI variants in tumor lesions in mice. iβ2GPI was incubated with plasmin to obtain nβ2GPI, and its N-terminal sequence was analyzed. nβ2GPI had at least one other cleavage site upstream of the β2GPIʼs domain V, whereas the former plasmin-cleavage site locates between K317 and T318. Both of intact and nicked β2GPI significantly inhibited the VEGF-A-induced cell proliferation and the tube formation of human umbilical vein endothelial cells (HUVECs). PET imaging visualized considerably distributed intensities of all tested β2GPI variants in tumor lesions of pancreatic tumor cell-xenografts. These results indicate that β2GPI may be physiologically and pathophysiologically important in the regulation of not only coagulation and fibrinolysis, but also angiogenesis

A Novel 89Zr-labeled DDS Device Utilizing Human IgG Variant (scFv): “Lactosome” Nanoparticle-Based Theranostics for PET Imaging and Targeted Therapy

“Theranostics,” a new concept of medical advances featuring a fusion of therapeutic and diagnostic systems, provides promising prospects in personalized medicine, especially cancer. The theranostics system comprises a novel 89Zr-labeled drug delivery system (DDS), derived from the novel biodegradable polymeric micelle, “Lactosome” nanoparticles conjugated with specific shortened IgG variant, and aims to successfully deliver therapeutically effective molecules, such as the apoptosis-inducing small interfering RNA (siRNA) intracellularly while offering simultaneous tumor visualization via PET imaging. A 27 kDa-human single chain variable fragment (scFv) of IgG to establish clinically applicable PET imaging and theranostics in cancer medicine was fabricated to target mesothelin (MSLN), a 40 kDa-differentiation-related cell surface glycoprotein antigen, which is frequently and highly expressed by malignant tumors. This system coupled with the cell penetrating peptide (CPP)-modified and photosensitizer (e.g., 5, 10, 15, 20-tetrakis (4-aminophenyl) porphyrin (TPP))-loaded Lactosome particles for photochemical internalized (PCI) driven intracellular siRNA delivery and the combination of 5-aminolevulinic acid (ALA) photodynamic therapy (PDT) offers a promising nano-theranostic-based cancer therapy via its targeted apoptosis-inducing feature. This review focuses on the combined advances in nanotechnology and material sciences utilizing the “89Zr-labeled CPP and TPP-loaded Lactosome particles” and future directions based on important milestones and recent developments in this platform

Clinical significance in the number of involved lymph nodes in patients that underwent surgery for pathological stage III-N2 non-small cell lung cancer

<p>Abstract</p> <p>Purpose</p> <p>This study investigated whether the number of involved lymph nodes is associated with the prognosis in patients that underwent surgery for pathological stage (p-stage) III/N2 NSCLC.</p> <p>Subjects</p> <p>This study evaluated 121 patients with p-stage III/N2 NSCLC.</p> <p>Results</p> <p>The histological types included 65 adenocarcinomas, 39 squamous cell carcinomas and 17 others. The average number of dissected lymph nodes was 23.8 (range: 6-55). The average number of involved lymph nodes was 5.9 (range: 1-23). The 5-year survival rate of the patients was 51.0% for single lymph node positive, 58.9% for 2 lymph nodes positive, 34.2% for 3 lymph nodes positive, and 30.0% for 4 lymph nodes positive, and 20.4% for more than 5 lymph nodes positive. The patients with either single or 2 lymph nodes positive had a significantly more favorable prognosis than the patients with more than 5 lymph nodes positive. A multivariate analysis revealed that the number of involved lymph nodes was a significant independent prognostic factor.</p> <p>Conclusion</p> <p>Surgery appears to be preferable as a one arm of multimodality therapy in p-stage III/N2 patients with single or 2 involved lymph nodes. The optimal incorporation of surgery into the multimodality approach therefore requires further clinical investigation.</p