gebhart/patrepeval huggingface dataset:
Significance of epithelial membrane antigen in the work‐up of problematic serous effusions (1995)

Differentiation of reactive and/or atypical mesothelial cells from malignant epithelial cells in serous effusions remains a frequent diagnostic problem. Since epithelial membrane antigen (EMA) positive malignant cells in serous effusions have been reported in almost all adenocarcinomas and most malignant mesotheliomas, immunoreactivity for EMA is felt to be less useful than other antibodies in the workup of problematic serous effusions. However, immunostaining of reactive and/or atypical benign mesothelial cells for EMA has not been well studied, with only a few series reporting either weak or negative staining for EMA. This study was undertaken to evaluate how often reactive and/or atypical appearing mesothelial cells stain positively for EMA. One hundred eighty serous effusions (115 pleural, 55 peritoneal, and 10 pericardial) from 123 females and 57 males ages 20 to 89 yr were evaluated in which an antibody panel including EMA was performed on cell blocks (141 cases), cytospins (36 cases), or both (3 cases). Of the 100 cytologically positive cases, EMA immunoreactivity was present in 97/100 (97%) cases. One EMA negative case suspicious for a metastatic renal cell carcinoma was lost to follow-up and not included in the analysis. The remaining three negative cases consisted of malignancies not expected to have EMA positive cells (small cell carcinoma, neuroblastoma, and synovial sarcoma). Therefore, EMA was positive in virtually 100% of the remaining malignant cases. In the 78 cytologically negative cases, EMA positivity was present in 3/78 (3.8%) cases. Clinical follow-up of up to 14 mo in these three cases revealed no evidence of malignancy.(ABSTRACT TRUNCATED AT 250 WORDS)
High levels of DNA index heterogeneity in advanced breast carcinomas. Evidence for DNA ploidy differences between lymphatic and hematogenous metastases (1993)

A marked DNA index heterogeneity can be found in primary and metastatic tumor sites when appropriate sampling is applied. There were no DNA ploidy subclasses, notably absent in either type of metastasis, indicating similar metastatic capacities of both DNA aneuploid and DNA diploid tumor stemlines in advanced breast carcinomas. The difference in DNA ploidy status between lymphatic and hematogenous metastases suggest that these metastases can be generated independently.
Combination Exposure to Zidovudine plus Sulfamethoxazole-Trimethoprim Diminishes B-Lymphocyte Immune Responses toPneumocystis murinaInfection in Healthy Mice (2006)

We have previously shown that zidovudine plus sulfamethoxazole-trimethoprim exposure decreases immune cell populations in the bone marrow of healthy mice by inducing apoptosis. The hypothesis of the current work was that this toxicity would have an adverse impact on the immune response. To determine this, BALB/c mice were treated with zidovudine, sulfamethoxazole-trimethoprim, the combination of both drugs, or vehicle only (control) via oral gavage for 21 days. On day 4 after dosing completion, the mice were infected intratracheally with 1x10(7) Pneumocystis murina organisms. Immune cell populations (in lung digest, bronchoalveolar lavage fluid, tracheobronchial lymph node, and bone marrow samples), the lung Pneumocystis burden, and serum Pneumocystis-specific antibody titers were determined at days 6, 10, and 20 postinfection. While total bone marrow cellularity was recovered by day 6 postinfection in the combination exposure group, B-cell numbers did not recover until 10 days postinfection, primarily due to the persistent depletion of the late pre-B-cell phenotype. The numbers of CD4+ and CD8+ T cells, as well as the numbers of total B cells and activated B cells in tracheobronchial lymph nodes, were decreased at days 10 and 20 as a result of zidovudine plus sulfamethoxazole-trimethoprim exposure compared to the numbers in the control group. No significant differences in lung lavage or lung digest cell populations were observed. There was a trend of a delay in Pneumocystis clearance in the combination treatment group, and Pneumocystis-specific serum immunoglobulin G titers were reduced at day 20 postinfection. Together, these data indicate that the combination of zidovudine and sulfamethoxazole-trimethoprim adversely affects the humoral immune response to Pneumocystis.
-765G > CCOX-2polymorphism may be a susceptibility marker for gastric adenocarcinoma in patients with atrophy or intestinal metaplasia (2006)

-765C carrier status should be considered as another susceptibility marker for gastric adenocarcinoma development in patients with atrophy or intestinal metaplasia.
Photoheterotrophic growth of Agmenellum quadruplicatum PR-6 (1986)

The unicellular cyanobacterium Agmenellum quadruplicatum PR-6 grows in the presence of light on agar containing 10 microM 3-(3,4 dichlorophenyl)-1,1-dimethylurea and 1 to 30 mM glycerol. A derivative strain, PR-6G2, was tolerant of 100 mM glycerol. Photoheterotrophic growth conditions had little effect on transformation competence but did decrease the viability of single cells plated onto agar, particularly cells of the parent strain.
Host species-specific usage of the TLR4-LPS receptor complex (2008)

Recognition of LPS depends on the interaction of at least three molecules forming the LPS-receptor complex. The most important ones, CD14, MD2 and Toll-like receptor (TLR) 4 share a high degree of homology between species. In the present study, we investigated the importance of species-specific restriction on the recognition of LPS using stably transfected HEK293 cell lines expressing either human or bovine LPS-receptor complex components. Species-specific MD2 appeared to confer LPS recognition, whereas species-specific CD14 only appeared to play a minor role. In addition to the recognition of LPS, there is evidence that the fusion (F) protein of respiratory syncytial virus (RSV), which is the most common viral respiratory pathogen during infancy world-wide, interacts with TLR4, and plays an important role in the initiation of the innate immune response. Our findings suggest that human and bovine RSV may activate human and bovine TLR4 receptors, respectively, in the presence of both MD2 and CD14. However, no clear role for the RSV F protein of either human or bovine RSV alone in stimulating TLR4-dependent NF-kappaB activation was observed.
Advanced Oxidation Protein Products Promote Inflammation in Diabetic Kidney through Activation of Renal Nicotinamide Adenine Dinucleotide Phosphate Oxidase (2008)

The involvement of inflammatory processes has been recognized in development and/or progression of diabetic nephropathy. However, the mechanisms involved in the pathogenesis of renal inflammation have not been completely understood. In this study, we tested the hypothesis that accumulation of advanced oxidation protein products (AOPPs), which occurs in diabetes, may promote inflammatory responses in diabetic kidney. Streptozotocin-induced diabetic rats were randomized to iv injection of vehicle, native rat serum albumin (RSA), and AOPPs-modified RSA (AOPPs-RSA) in the presence or absence of oral administration of apocynin. A control group was followed concurrently. Compared with RSA- or vehicle-treated diabetic rats, AOPPs-RSA-treated animals displayed significant increase in renal macrophage infiltration and overexpression of monocyte chemoattractant protein-1 and TGF-beta1. This was associated with deteriorated structural and functional abnormalities of diabetic kidney, such as glomerular hypertrophy, fibronectin accumulation, and albuminuria. AOPP challenge significantly increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent superoxide generation in renal homogenates and up-regulated membrane expression of renal NADPH oxidase subunits p47(phox) and gp91(phox). All these AOPPs-induced perturbations in diabetic kidney could be prevented by the NADPH oxidase inhibitor apocynin. These data suggest that chronic accumulation of AOPPs may promote renal inflammation in diabetes probably through activation of renal NADPH oxidase.
Influenza Virus Aerosols in Human Exhaled Breath: Particle Size, Culturability, and Effect of Surgical Masks (2013)

The CDC recommends that healthcare settings provide influenza patients with facemasks as a means of reducing transmission to staff and other patients, and a recent report suggested that surgical masks can capture influenza virus in large droplet spray. However, there is minimal data on influenza virus aerosol shedding, the infectiousness of exhaled aerosols, and none on the impact of facemasks on viral aerosol shedding from patients with seasonal influenza. We collected samples of exhaled particles (one with and one without a facemask) in two size fractions ("coarse">5 µm, "fine"≤5 µm) from 37 volunteers within 5 days of seasonal influenza onset, measured viral copy number using quantitative RT-PCR, and tested the fine-particle fraction for culturable virus. Fine particles contained 8.8 (95% CI 4.1 to 19) fold more viral copies than did coarse particles. Surgical masks reduced viral copy numbers in the fine fraction by 2.8 fold (95% CI 1.5 to 5.2) and in the coarse fraction by 25 fold (95% CI 3.5 to 180). Overall, masks produced a 3.4 fold (95% CI 1.8 to 6.3) reduction in viral aerosol shedding. Correlations between nasopharyngeal swab and the aerosol fraction copy numbers were weak (r = 0.17, coarse; r = 0.29, fine fraction). Copy numbers in exhaled breath declined rapidly with day after onset of illness. Two subjects with the highest copy numbers gave culture positive fine particle samples. Surgical masks worn by patients reduce aerosols shedding of virus. The abundance of viral copies in fine particle aerosols and evidence for their infectiousness suggests an important role in seasonal influenza transmission. Monitoring exhaled virus aerosols will be important for validation of experimental transmission studies in humans.
Differential stimulation of collagenase and chemotactic activity in fibroblasts derived from rat wound repair tissue and human skin by growth factors (1989)

Epidermal growth factor and cartilage-derived basic fibroblast growth factor (EGF and CD-bFGF) are mitogens shown to increase the rate of wound repair in animal models. In addition to being a mitogen for granulation tissue, CD-bFGF stimulates the recruitment of cells to the wound site. CD-bFGF and a closely-related chondrosarcoma-derived fibroblast growth factor stimulated chemotaxis of granulation tissue cells in vitro, each factor having a maximum activity at a concentration of 55 pM. Epidermal growth factor was also a potent chemoattractant for rat granulation tissue fibroblasts; however, maximum activity was obtained at 1.7 nM. Cells from all stages of wound repair were chemotactically responsive to these factors, but there was some attenuation of the response to bFGF in cells derived from fully-organized day 28 granulation tissue. Collagenase-catalyzed restructuring of collagen, an additional significant feature of wound repair, is probably critical to cell movement in an extracellular matrix. Cells derived from organizing (6-day old) sponge granulation tissue secreted latent collagenase constitutively in vitro. In the presence of serum, the production of collagenase was stimulated three-four fold by 1.8 nM bFGF derived either from cartilage or chondrosarcoma. When serum was present, as at a wound site, collagenase production was not enhanced by the addition of EGF. Cells from fully organized, day 21 sponge granulation tissue did not secrete latent collagenase constitutively and could not be stimulated to do so by the addition of EGF, bFGF, or phorbol ester. Human skin fibroblast collagenase production was also stimulated by bFGF and was refractory to EGF. While both classes of growth factor have the ability to promote wound healing, the varying responses they elicit in cell populations from the wound site emphasize the different pathways of cellular activation.
The Third Signal Cytokine IL-12 Rescues the Anti-Viral Function of Exhausted HBV-Specific CD8 T Cells (2013)

Optimal immune activation of naïve CD8 T cells requires signal 1 mediated by the T cell receptor, signal 2 mediated by co-stimulation and signal 3 provided by pro-inflammatory cytokines. However, the potential for signal 3 cytokines to rescue anti-viral responses in functionally exhausted T cells has not been defined. We investigated the effect of using third signal cytokines IL-12 or IFN-α to rescue the exhausted CD8 T cell response characteristic of patients persistently infected with hepatitis B virus (HBV). We found that IL-12, but not IFN-α, potently augmented the capacity of HBV-specific CD8 T cells to produce effector cytokines upon stimulation by cognate antigen. Functional recovery mediated by IL-12 was accompanied by down-modulation of the hallmark inhibitory receptor PD-1 and an increase in the transcription factor T-bet. PD-1 down-regulation was observed in HBV but not CMV-specific T cells, in line with our finding that the highly functional CMV response was not further enhanced by IL-12. IL-12 enhanced a number of characteristics of HBV-specific T cells important for viral control: cytotoxicity, polyfunctionality and multispecificity. Furthermore, IL-12 significantly decreased the pro-apoptotic molecule Bim, which is capable of mediating premature attrition of HBV-specific CD8 T cells. Combining IL-12 with blockade of the PD-1 pathway further increased CD8 functionality in the majority of patients. These data provide new insights into the distinct signalling requirements of exhausted T cells and the potential to recover responses optimised to control persistent viral infections.
Safety and biodistribution of 99mTechnetium-labeled anti-CD44v6 monoclonal antibody BIWA 1 in head and neck cancer patients. (2000)

The CD44 protein family consists of isoforms, encoded by standard exons and up to nine alternatively spliced variant exons (v2-v10), which are expressed in a tissue-specific way. Expression of v6-containing variants (CD44v6) has been related to aggressive behavior of various tumor types and was shown to be particularly high in squamous cell carcinoma (SCC). Therefore, CD44v6 might be a suitable target for radioimmunoscintigraphy (RIS) and therapy. The present study evaluates the novel high-affinity murine anti-CD44v6 monoclonal antibody (MAb) BIWA 1 for its safety and targeting potential in patients with SCC of the head and neck (HNSCC). Twelve HNSCC patients, who had planned to undergo resection of the primary tumor and neck dissection, were included. Preoperatively, 2, 12, or 52 mg of 99nTc-labeled MAb BIWA 1 was administered. RIS results obtained 21 h after injection were compared with palpation, computed tomography, and magnetic resonance imaging, with histopathology as the gold standard. Moreover, biodistribution of BIWA 1 was evaluated by radioactivity measurement in blood and bone marrow and in biopsies from the surgical specimen obtained 40 h after injection. The distribution of BIWA 1 in tumor biopsies was analyzed by immunohistochemistry. BIWA 1 integrity in the blood was assessed by high-performance liquid chromatography and related to soluble CD44v6 levels in serum samples. No drug-related adverse events were observed. Human antimouse antibody responses were observed in 11 patients. The diagnostic efficacy of RIS appeared to be comparable for the three BIWA 1 dose levels and for the four diagnostic methods. Besides activity uptake in tumor tissue, minimal accumulation of activity was observed in mouth, lungs, spleen, kidney, bone marrow, and scrotal area. Analysis of tissue biopsies revealed high uptake in tumors, with a mean value of 14.2+/-8.4% of the injected dose/kg tumor tissue and a mean tumor:blood ratio of 2.0+/-1.4 at 40 h after injection. Differences among the three dose groups were not statistically significant, although a trend toward lower uptake in the highest dose group was noted. Distribution of BIWA 1 throughout the tumor was heterogeneous for all dose groups, which might be related to the high affinity of the MAb. The mean biological half-life in blood (34.5+/-6.1 h) was not dose dependent. Extensive complex formation of BIWA 1 was observed in the 2-mg group, most probably with soluble CD44v6 present in the blood, and complex formation relatively diminished upon increase of the MAb dose. BIWA 1 is a promising MAb for targeting HNSCC because it can be safely administered to HNSCC patients, while it shows high and selective tumor uptake. However, BIWA 1 is immunogenic, and therefore a chimerized or humanized derivative of BIWA 1 with intermediate affinity will be used in future clinical trials.
Effect of various adjuvants on the antibody response of mice to pneumococcal polysaccharides. (1989)

Adjuvant effects on the serum antibody response to pneumococcal polysaccharide (pps) types 3 and 14 were studied in BALB/c mice. First, dose responses were established for the two pps types and were found to be entirely different. High (5 micrograms) and low (0.005 microgram) doses of pps 3 induced antigen-specific unresponsiveness and suppression, while 0.1 microgram induced an optimal response. The secondary response to a single dose of killed pneumococci or 0.1 microgram of pps 3 injected 2 weeks later was not higher than the primary response. Nu/Nu, athymic BALB/c mice showed high but not low dose tolerance to pps 3. In contrast, no convincing evidence for high dose tolerance to pps 14 was obtained: 25 micrograms of pps 14 induced an optimal response, whereas 0.2-0.5 microgram induced antigen-specific suppression. Secondary anti-pps 14 IgM and IgG responses, even after optimal primary doses, were only slightly higher than primary responses to a single dose of killed bacteria. Athymic BALB/c mice showed lower IgG antibody responses than euthymic mice to pps 14. Injection of detoxified endotoxin (D-LPS) 2-4 days after antigen enhanced both primary and secondary responses and reversed high dose tolerance induction. Injection of D-LPS also at least partially prevented the induction of low dose tolerance as did injection of interleukin-1, but normuramyl dipeptide (nor-MDP) failed to affect the responses to pps 3 and 14. Coupling of muramyl tripeptide to pps 3 rendered the pps more immunogenic. Administration of emulsified pps in squalene arlacel, particularly with nor-MDP incorporated in the mixture, appeared to induce a better 7S antibody response than did pps in saline, but these serum antibody levels were not sustained at a high level. Pretreatment with IgD or simultaneous injection of IgD with pps 14 enhanced both primary and secondary responses. The response to pps 3 was only slightly enhanced and low dose tolerance was not prevented by pretreatment with IgD.
VAMP8 facilitates cellular proliferation and temozolomide resistance in human glioma cells (2014)

Our findings identified VAMP8 as a novel oncogene by promoting cell proliferation and therapeutic resistance in glioma. Targeting VAMP8 may serve as a potential therapeutic regimen for the treatment of glioma.
Prolongation of Survival in Metastatic Melanoma After Active Specific Immunotherapy With a New Polyvalent Melanoma Vaccine (1992)

A new polyvalent melanoma cell vaccine (MCV) was administered to 136 stage IIIA and IV (American Joint Committee on Cancer) melanoma patients. Induction of cell-mediated and humoral immune responses to common melanoma-associated antigens present on autologous melanoma cells was observed in patients receiving the new MCV. This was accompanied by increased activation of tumor-infiltrating lymphocytes. Survival correlated significantly with delayed cutaneous hypersensitivity (p = 0.0066) and antibody responses to MCV (p = 0.0117). Of 40 patients with evaluable disease, nine (23%) had regressions (three complete). From our historical database of 126 stage IIIA and 1275 stage IV melanoma patients, there were no significant changes in the natural history of metastatic melanoma during the past 20 years. Univariate and multivariate analyses demonstrated prognostic significance for site of metastases (p = 0.0001) and immunotherapy with the new MCV (p = 0.0001). Overall our new MCV increased the median and 5-year survival of stage IIIA melanoma patients with regional soft tissue metastases twofold (p = 0.00024), and stage IV patients threefold (p = 0.0001) compared with previous immunotherapy and other treatments.
Some Results on Optimal Dividend Problem in Two Risk Models (2010)

The compound Poisson risk model and the compound Poisson risk model perturbed by diffusion are considered in the presence of a dividend barrier with solvency constraints. Moreover, it extends the known result due to [1]. Ref.
Conjugation of a brain-penetrant peptide with neurotensin provides antinociceptive properties (2014)

Neurotensin (NT) has emerged as an important modulator of nociceptive transmission and exerts its biological effects through interactions with 2 distinct GPCRs, NTS1 and NTS2. NT provides strong analgesia when administered directly into the brain; however, the blood-brain barrier (BBB) is a major obstacle for effective delivery of potential analgesics to the brain. To overcome this challenge, we synthesized chemical conjugates that are transported across the BBB via receptor-mediated transcytosis using the brain-penetrant peptide Angiopep-2 (An2), which targets LDL receptor-related protein-1 (LRP1). Using in situ brain perfusion in mice, we found that the compound ANG2002, a conjugate of An2 and NT, was transported at least 10 times more efficiently across the BBB than native NT. In vitro, ANG2002 bound NTS1 and NTS2 receptors and maintained NT-associated biological activity. In rats, i.v. ANG2002 induced a dose-dependent analgesia in the formalin model of persistent pain. At a dose of 0.05 mg/kg, ANG2002 effectively reversed pain behaviors induced by the development of neuropathic and bone cancer pain in animal models. The analgesic properties of ANG2002 demonstrated in this study suggest that this compound is effective for clinical management of persistent and chronic pain and establish the benefits of this technology for the development of neurotherapeutics.
Overview of Alternative Oligonucleotide Chemistries for Exon Skipping (2012)

The chemistry of the oligonucleotide backbone is crucial to obtaining high activity in vivo in exon skipping applications. Apart from the ability to bind strongly and sequence-specifically to pre-mRNA targets, the type of backbone also influences cell delivery, in vivo pharmacology, bio-distribution, toxicology, and ultimately the therapeutic use in humans. Reviewed here are classes of oligonucleotide commonly used for exon skipping applications, namely negatively charged backbones typified by RNA analogues having 2'-O-substitution and a phosphorothioate linkage and charge-neutral backbones such as PNA and PMO. Also discussed are peptide conjugates of PNA and PMO that enhance cellular and in vivo delivery and their potential for drug development. Finally, the prospects for development of other analogue types in exon skipping applications are outlined.
Improvement of Light-Load Efficiency Using Width-Switching Scheme for CMOS Transistors (2005)

This paper presents a derivation of the optimum width of transistors to minimize losses in monolithic CMOS buck converters. The high optimal width requires a tapered inverter chain gate driver. A technique called "width switching" is presented. It can be integrated with the inverter chain to maintain maximum converter efficiency over a wide power range, particularly at light load. Experimental results are presented from a chip containing CMOS transistors optimized for power levels between 50 mW and 200 mW. Challenges in implementing the width-switching scheme and other applications are also discussed.