Progressive nodule-like lesions on bilateral lower limbs.

Pancreatic panniculitis is a rare disease characterized by subcutaneous fat necrosis. It could be the result of an associated pancreatic tumor. Herein, we reported a 63-year-old man who presented with progressive bilateral lower limb edema accompanied with nodule-like lesions for 1 month. His serum lipase was 3,927 U/L (normal, 0-160 U/L). Histopathology of the skin specimen revealed lobular panniculitis, favoring a diagnosis of pancreatic panniculitis. Abdominal computed tomography (CT) scan with contrast showed a huge mass in his left upper quadrant. Endoscopic ultrasound showed a mixed echoic tumor, measuring 11.9 × 7.8 cm in dimensions, originating from the pancreatic tail. Biopsy performed via an endoscopic ultrasound showed a poorly differentiated acinar cell carcinoma. Because of the unresectable status of the tumor, the patient underwent chemotherapy with paclitaxel and gemcitabine. After chemotherapy, his skin lesions improved progressively. It is important to treat pancreatic panniculitis with its underlying pancreatic disease.

Behçet's disease-induced massive small intestinal bleeding successfully treated with adalimumab.

We herein report a case of Behçet's disease in a 27-year-old female who suffered from generalized skin rashes for one week. After hospitalization, massive bloody stools accompanying hypovolemic shock occurred. Emergency abdominal computed tomography-angiography failed to detect the bleeding source. Esophagogastroduodenoscopy also demonstrated no definite bleeding points. Ileocolonoscopy showed multiple large and deep ulcers with some blood coating and mild oozing in the terminal ileum. We initially performed epinephrine injection and hemoclips for her intestinal bleeding. However, massive bloody stools still continued. Thus, we prescribed a loading dose of 160 mg adalimumab followed by weekly 80 mg adalimumab subcutaneous injections to the patient. Following this treatment, her gastrointestinal bleeding gradually subsided and completely stopped within a few days. After three-week therapy with adalimumab, capsule endoscopy showed several healing ulcers without bleeding in the distal to the terminal ileum. She continues to be treated with adalimumab, azathioprine, and mesalazine without recurrent bleeding.

Genomic indicators in the blood predict drug-induced liver injury.

Genomic biomarkers for the detection of drug-induced liver injury (DILI) from blood are urgently needed for monitoring drug safety. We used a unique data set as part of the Food and Drug Administration led MicroArray Quality Control Phase-II (MAQC-II) project consisting of gene expression data from the two tissues (blood and liver) to test cross-tissue predictability of genomic indicators to a form of chemically induced liver injury. We then use the genomic indicators from the blood as biomarkers for prediction of acetaminophen-induced liver injury and show that the cross-tissue predictability of a response to the pharmaceutical agent (accuracy as high as 92.1%) is better than, or at least comparable to, that of non-therapeutic compounds. We provide a database of gene expression for the highly informative predictors, which brings biological context to the possible mechanisms involved in DILI. Pathway-based predictors were associated with inflammation, angiogenesis, Toll-like receptor signaling, apoptosis, and mitochondrial damage. The results show for the first time and support the hypothesis that genomic indicators in the blood can serve as potential diagnostic biomarkers predictive of DILI.

Blood gene expression signatures predict exposure levels.

To respond to potential adverse exposures properly, health care providers need accurate indicators of exposure levels. The indicators are particularly important in the case of acetaminophen (APAP) intoxication, the leading cause of liver failure in the U.S. We hypothesized that gene expression patterns derived from blood cells would provide useful indicators of acute exposure levels. To test this hypothesis, we used a blood gene expression data set from rats exposed to APAP to train classifiers in two prediction algorithms and to extract patterns for prediction using a profiling algorithm. Prediction accuracy was tested on a blinded, independent rat blood test data set and ranged from 88.9% to 95.8%. Genomic markers outperformed predictions based on traditional clinical parameters. The expression profiles of the predictor genes from the patterns extracted from the blood exhibited remarkable (97% accuracy) transtissue APAP exposure prediction when liver gene expression data were used as a test set. Analysis of human samples revealed separation of APAP-intoxicated patients from control individuals based on blood expression levels of human orthologs of the rat discriminatory genes. The major biological signal in the discriminating genes was activation of an inflammatory response after exposure to toxic doses of APAP. These results support the hypothesis that gene expression data from peripheral blood cells can provide valuable information about exposure levels, well before liver damage is detected by classical parameters. It also supports the potential use of genomic markers in the blood as surrogates for clinical markers of potential acute liver damage.

Fluorescence signals of core-shell quantum dots enhanced by single crystalline gold caps on silicon nanowires.

We use nanoscale (20-300 nm in diameter) single crystalline gold (Au)-caps on silicon nanowires (NWs) grown by the vapor-liquid-solid (VLS) growth mechanism to enhance the fluorescence photoluminescence (PL) signals of highly dilute core/shell CdSeTe/ZnS quantum dots (QDs) in aqueous solution (10(-5) M). For NWs without Au-caps, as they appear, for example, after Au etching in aqua regia or buffered KI/I(2)-solution, essentially no fluorescence signal of the same diluted QDs could be observed. Fluorescence PL signals were measured using excitation with a laser wavelength of 633 nm. The signal enhancement by single crystalline, nanoscale Au-caps is discussed and interpreted based on finite element modeling (FEM).

Fluorescence signals of quantum dots influenced by spatially controlled array structures.

Fluorescence signals of quantum dots (QDs) influenced by different array structures of gold-coated silicon nanorods (SiNRs) were investigated via experimental observations and two-dimensional (2D) finite element method (FEM) simulations. On the densest gold-coated SiNRs array structure, the highest QD fluorescence quenching rates were observed and on the sparsest array structure, the highest QD fluorescence enhancement rates were observed. By developing a new technique which obtains the optical image of the array structures without losing information about the QD locations, we were able to further investigate how the QD fluorescence is influenced by spatially controlled array structures.

Observation of localized surface plasmons in spatially controlled array structures.

We observed the reflectance spectra of three different nano-scale array structures of Au-coated silicon nanorods. The trends of the reflectance spectra indicate that the localized surface plasmon modes can be spatially controlled by manipulating geometric parameters, namely the lattice constants of the array. In addition, the experimental results were compared with 2D numerical simulations based on the finite element method. Satisfactory agreement between the experimental observations and numerical results was obtained.

Gram-negative bacillary meningitis in adults.

To evaluate the clinical aspects of gram-negative bacillary meningitis (GNBM), we reviewed 41 adult patients with bacteriologically proven gram-negative bacillary meningitis, seen from 1985 to 1990. Thirty-two patients had post-neurosurgical GNBM and nine patients had spontaneous GNBM. Spontaneous GNBM appeared to have a sudden onset, a relatively fulminant course, and was caused most often by Escherichia coli. Post-neurosurgical GNBM, however, had a more insidious onset, a more protracted course, and was more often caused by nosocomial organisms which were resistant to multiple antibiotics. The overall mortality was 39%. Patients treated with combined aminoglycoside therapy had a lower mortality rate than those treated with intravenous aminoglycoside (17% vs 48%). The use of third-generation cephalosporins has made a significant therapeutic advance in the treatment of GNBM, with a lower mortality of 21%. We recommend treatment of GNBM with third-generation cephalosporins and aminoglycosides. If aminoglycosides are to be employed, it is suggested that they be administered both intravenously and directly into the central nervous system.

Cartilage collagen analysis in the chondrodystrophies.

A simple and reproducible method for analyzing small samples of cartilage collagens was developed. Following extraction with guanidine HCl, the cartilage specimens were digested directly with CNBr and the resultant peptides separated by gel-permeation high-performance liquid chromatography. Resting cartilage collagen CNBr peptide maps differed from normal in two inherited chondrodystrophies, achondrogenesis II and spondyloepiphyseal dysplasia congenita.

Achondrogenesis type II, abnormalities of extracellular matrix.

Immune and lectin histochemical and microchemical methods were employed to study growth cartilage from seven cases of achondrogenesis type II (Langer-Saldino). The normal architecture of the epiphyseal and growth plate cartilage was replaced by a morphologically heterogeneous tissue. Some areas were comprised of vascular canals surrounded by extensive fibrous tissue and enlarged cells that had the appearance and histochemical characteristics of hypertrophic chondrocytes. Other areas contained a mixture of cells ranging from small to the enlarged chondrocytes. The extracellular matrix in the latter areas was more abundant and had characteristics of both precartilage mesenchymal matrix and typical cartilage matrix; it contained types I and II collagen, cartilage proteoglycan, fibronectin, and peanut agglutinin binding glycoconjugate(s). Peptide mapping of cyanogen bromide cartilage collagen peptides revealed the presence of types I and II collagen. These observations could be explained by a defect in the biosynthesis of type II collagen or in chondrocyte differentiation.

Cyclosporine transfer from low- and high-density lipoproteins is partially influenced by lipid transfer protein I triglyceride transfer activity.

PURPOSE: The purpose of this study was to determine if lipid transfer protein (LTP I) facilitated triglyceride (TG) transfer activity regulates the plasma lipoprotein distribution of cyclosporine (CSA). METHODS: To assess the influence of drug concentration and incubation time on the plasma lipoprotein distribution of CSA, 3H-CSA (50 to 1000 ng/ml) was incubated in human plasma for 5 to 120 minutes at 37 degrees C. To determine if LTP I facilitated TG transfer activity regulates the plasma lipoprotein distribution of CSA, 3H-Triolein (TG)- or 3H-CSA-enriched high-density lipoproteins (HDL) or low-density lipoproteins (LDL) were incubated in T150 buffer (50 mM Tris-HCl, 150 mM NaCl, 0.02% Sodium Azide, 0.01% Disodium EDTA), pH 7.4 which contained a 3H-Triolein (TG) or 3H-CSA-free lipoprotein counterpart +/- exogenous LTP I (1.0 microg protein/ml) or in delipidated human plasma which contained 1.0 microg protein/ml of endogenous LTP I for 90 minutes at 37 degrees C. These experiments were repeated in the presence of a monoclonal antibody TPI (15 microg protein/ml) directed against LTP I. RESULTS: No differences in CSA lipoprotein distribution were observed following incubation of the drug at varying concentrations and incubation times in human plasma. The percent transfer of TG from HDL to LDL and LDL to HDL was greater in T150 buffer than in human plasma. However, the percent transfer of CSA from only LDL to HDL was greater in T150 buffer than in human plasma. Furthermore, undetectable 3H-CSA transfer from HDL to LDL in T150 buffer containing purified LTP I was observed. In addition, when the percent transfer of TG and CSA were determined in the presence of TPI, the percent transfer of TG and CSA from only LDL to HDL were significantly decreased in T150 buffer and human plasma compared to controls. CONCLUSIONS: These findings suggest that the transfer of CSA between different lipoprotein particles is only partially influenced by LTP I facilitated TG transfer activity.