gebhart/patrepeval huggingface dataset:
Amino acids and peptides. XI. Synthesis of .MU.-Conotoxin GIIIA: A chemical probe for sodium channels. (1990)

mu-Conotoxin GIIIA, a 22 amino acid peptide paralytic toxin which inhibits the muscle voltage-activated sodium channels, was synthesized by a solid phase method. No purification of intermediates was necessary for the synthesis, and a simple air oxidation of the deprotected crude peptide gave the desired toxin. By all criteria applied, the synthetic material was indistinguishable from the authentic natural toxin.
Successful Treatment of Membranous Glomerulonephritis with Rituximab in Calcineurin Inhibitor-Dependent Patients (2009)

In patients with MGN with long-term CNI dependence, rituximab can be an effective tool to overcome dependence on CNI, thus avoiding the risk of nephrotoxicity related to the chronic exposure to these drugs.
The Metabolic Significance of Leptin in Humans: Gender-Based Differences in Relationship to Adiposity, Insulin Sensitivity, and Energy Expenditure* (1997)

Leptin is an adipocyte-derived hormone that interacts with a putative receptor(s) in the hypothalamus to regulate body weight. The relationship of leptin to metabolic abnormalities associated with obesity together with hormonal and substrate regulation of leptin have not been extensively studied. Therefore, 116 subjects (62 men and 54 women) with a wide range of body weight [body mass index (BMI), 17-54 kg/m2] were characterized on a metabolic ward with regard to body composition, glucose intolerance, insulin sensitivity, energy expenditure, substrate utilization, and blood pressure. Eighty-five of the subjects had normal glucose tolerance (50 men and 35 women), and 31 had noninsulin-dependent diabetes mellitus (12 men and 19 women). In both men and women, fasting leptin levels were highly correlated with BMI (r = 0.87 and r = 0.88, respectively) and percent body fat (r = 0.82 and r = 0.88, respectively; all P < 0.0001). However, men exhibited lower leptin levels at any given measure of obesity. Compared with those in men, leptin levels rose 3.4-fold more rapidly as a function of BMI in women [leptin = 1.815 (BMI)-31.103 in women; leptin = 0.534 (BMI)-8.437 in men] and 3.2 times more rapidly as a function of body fat [leptin = 1.293 (% body fat)-24.817 in women; leptin = 0.402 (% body fat)-3.087 in men]. Hyperleptinemia was associated with insulin resistance (r = -0.57; P < 0.0001) and high waist to hip ratio (r = 0.75; P < 0.0001) only in men. On the other hand, during the hyperinsulinemic euglycemic clamp studies, hyperinsulinemia acutely increased leptin concentrations (20%) only in women. There was no correlation noted between fasting leptin levels and either resting energy expenditure or insulin-induced thermogenesis in men or women (P = NS). In stepwise and multiple regression models with leptin as the dependent variable, noninsulin-dependent diabetes mellitus did not enter the equations at a statistically significant level. The data indicate that there are important gender-based differences in the regulation and action of leptin in humans. Serum leptin levels increase with progressive obesity in both men and women. However, for any given measure of obesity, leptin levels are higher in women than in men, consistent with a state of relative leptin resistance. These findings have important implications regarding differences in body composition in men and women. The observation that serum leptin is not related to energy expenditure rates suggests that leptin regulates body fat predominantly by altering eating behavior rather than calorigenesis.
The role of monocyte chemotactic protein-1 (MCP-1) in the recruitment of monocytes and CD4+ T cells during a pulmonary Cryptococcus neoformans infection (1995)

Cryptococcus neoformans is acquired via the respiratory tract and is the leading cause of fatal mycosis in AIDS. Development of a T cell-mediated pulmonary inflammatory response is critical for clearance of this pathogen; however, the chemotactic factors that mediate inflammatory cell recruitment into the lungs have not been identified. In the present study, the bronchoalveolar lavage (BAL) fluid levels of the C-C chemokine monocyte chemotactic protein-1 (MCP-1) and the recruitment of inflammatory cells both increased following pulmonary infection with C. neoformans. The kinetics of MCP-1 production in the lungs correlated most closely with the recruitment of CD4+ T cells and monocytes/macrophages. Administration of neutralizing anti-MCP-1 Abs in vivo reduced the BAL fluid levels of MCP-1, decreased the recruitment of both macrophages (> 95%) and CD4+ T cells (76 +/- 9%), and inhibited cryptococcal clearance. Although no in vitro neutrophil or B cell chemotactic activity has been reported for MCP-1, recruitment of these leukocytes was also decreased in anti-MCP-1-treated mice (most likely an indirect effect of reducing the number of CD4+ T cells and macrophages). Neutralization of MCP-1 also resulted in decreased BAL fluid levels of TNF-alpha and IL-6. This is the first demonstration of a role for MCP-1 in clearance of an infection, and provides direct evidence that MCP-1 plays a critical role in the T cell-dependent immune response to C. neoformans.
Task–specific impairments and enhancements induced by magnetic stimulation of human visual area V5 (1998)

Transcranial magnetic stimulation (TMS) can be used to simulate the effects of highly circumscribed brain damage permanently present in some neuropsychological patients, by reversibly disrupting the normal functioning of the cortical area to which it is applied. By using TMS we attempted to recreate deficits similar to those reported in a motion-blind patient and to assess the specificity of deficits when TMS is applied over human area V5. We used six visual search tasks and showed that subjects were impaired in a motion but not a form 'pop-out' task when TMS was applied over V5. When motion was present, but irrelevant, or when attention to colour and form were required, TMS applied to V5 enhanced performance. When attention to motion was required in a motion-form conjunction search task, irrespective of whether the target was moving or stationary, TMS disrupted performance. These data suggest that attention to different visual attributes involves mutual inhibition between different extrastriate visual areas.
Deletion of Chromosome 4q Predicts Outcome in Stage II Colon Cancer Patients (2010)

Background : Around 30% of all stage II colon cancer patients will relapse and die of their disease. At present no objective parameters to identify high-risk stage II colon cancer patients, who will benefit from adjuvant chemotherapy, have been established. With traditional histopathological features definition of high-risk stage II colon cancer patients is inaccurate. Therefore more objective and robust markers for prediction of relapse are needed. DNA copy number aberrations have proven to be robust prognostic markers, but have not yet been investigated for this specific group of patients. The aim of the present study was to identify chromosomal aberrations that can predict relapse of tumor in patients with stage II colon cancer. Materials and Methods : DNA was isolated from 40 formaldehyde fixed paraffin embedded stage II colon cancer samples with extensive clinicopathological data. Samples were hybridized using Comparative Genomic Hybridization (CGH) arrays to determine DNA copy number changes and microsatellite stability was determined by PCR. To analyze differences between stage II colon cancer patients with and without relapse of tumor a Wilcoxon rank-sum test was implemented with multiple testing correction. Results : Stage II colon cancers of patients who had relapse of disease showed significantly more losses on chromosomes 4, 5, 15q, 17q and 18q. In the microsatellite stable (MSS) subgroup ( n =28), only loss of chromosome 4q22.1–4q35.2 was significantly associated with disease relapse (p &lt; 0.05, FDR &lt; 0.15). No differences in clinicopathological characteristics between patients with and without relapse were observed. Conclusion : In the present series of MSS stage II colon cancer patients losses on 4q22.1–4q35.2 were associated with worse outcome and these genomic alterations may aid in selecting patients for adjuvant therapy.
Vascular Endothelial Growth Factor-Trap Overcomes Defects in Dendritic Cell Differentiation but Does Not Improve Antigen-Specific Immune Responses (2007)

Inhibition of VEGF signaling may improve differentiation of dendritic cells in cancer patients. However, it was not sufficient to improve immune responses. This shows multifaceted nature of immune deficiency and points out to the need for complex approach to modulation of immune reactivity in cancer.
The role of macrophages in the immunoadjuvant action of liposomes: effects of elimination of splenic macrophages on the immune response against intravenously injected liposome-associated albumin antigen. (1989)

The primary antibody response to intravenously administered and liposome-associated human serum albumin (HSA) was studied in mice under conditions where no response could be detected against the non-liposome-associated form of the antigen. The positive response against the antigen, entrapped in and/or exposed on the surfaces of liposomes, thus resulted from the adjuvant action of the liposomes. In mice intravenously injected with dichloromethylene diphosphonate (C12MDP) also entrapped in liposomes, all red pulp macrophages, marginal metallophilic macrophages and marginal zone macrophages had disappeared from the spleen 2 days after administration. Twenty-two days after such a treatment red pulp macrophages and marginal metallophilic macrophages had reappeared, but marginal zone macrophages were still absent. In mice injected with liposome-associated HSA at 2 days after treatment with the C12MDP liposomes, anti-HSA responses were severely depressed, but administration of the liposome-associated antigen 22 days after C12MDP liposomes elicited a normal response. These results point to a role of splenic macrophages in the processing of liposome-associated antigens, but marginal zone macrophages, which are located close to the open ends of the white pulp capillaries and thus are the first macrophages to meet the antigens arriving in the marginal zone are not required.
Induction of Apoptosis in Placentas of Pregnant Mice Exposedto Lipopolysaccharides: Possible Involvement of Fas/Fas Ligand System1 (2000)

To explore the pathogenesis in placental dysfunction and abruptio placentae, we analyzed the occurrence of placental cell apoptosis and the role of Fas and Fas ligand (L) in that process in an inflammatory placental dysfunction model of pregnant mice, using lipopolysaccharides (LPS). In the present study, Day 13 pregnant mice were injected i.p. with LPS (50 microg/kg) or saline as a control, and the placentas were isolated at various time points after the injection. Analysis of the isolated DNA in agarose-gel electrophoresis revealed a typical ladder pattern of bands consisting of 180-200 base pairs (bp), which is regarded as a hallmark of apoptosis. The intensity of the bands increased time-dependently, reaching a maximum level at 12 h after LPS injection. In accord with the biochemical data, histochemical analysis using terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) revealed that nuclei positive for double-stranded DNA breaks were found in decidua, diploid trophoblasts in the basal zone, and spongiotrophoblasts. The number of positive nuclei was maximized at 12 h after LPS injection. As a next step, we investigated the possible involvement of Fas and Fas L in the induction of apoptosis of the placental cells after LPS injection. Western blot analysis indicated that LPS increased the expression of Fas and Fas L in the placenta by about 4-fold at 12 h and 18 h, respectively, after injection. The cells expressing Fas and Fas L were identified, using immunohistochemistry and nonradioactive in situ hybridization, as decidua, diploid trophoblasts in the basal zone, and spongiotrophoblasts. Furthermore, when the expression of 4-hydroxy-2-nonenal (HNE)-modified proteins was assessed to evaluate the relation of oxidative stress elicited by LPS to the induction of apoptosis, once again decidua, diploid trophoblasts in the basal zone, and spongiotrophoblasts were positive. Therefore, the placental dysfunction by LPS may be brought about by the Fas-mediated apoptosis of various placental cells in a paracrine/autocrine fashion, possibly under the influence of oxidative stress.
Developments in the prediction of type 1 diabetes mellitus, with special reference to insulin autoantibodies (2005)

The prodromal phase of type 1 diabetes is characterised by the appearance of multiple islet-cell related autoantibodies (Aab). The major target antigens are islet-cell antigen, glutamic acid decarboxylase (GAD), protein-tyrosine phosphatase-2 (IA-2) and insulin. Insulin autoantibodies (IAA), in contrast to the other autoimmune markers, are the only beta-cell specific antibodies. There is general consensus that the presence of multiple Aab (> or = 3) is associated with a high risk of developing diabetes, where the presence of a single islet-cell-related Aab has usually a low predictive value. The most commonly used assay format for the detection of Aab to GAD, IA-2 and insulin is the fluid-phase radiobinding assay. The RBA does not identify or measure Aab, but merely detects its presence. However, on the basis of molecular studies, disease-specific constructs of GAD and IA-2 have been employed leading to somewhat improved sensitivity and specificity of the RBA. Serological studies have shown epitope restriction of IAA that can differentiate diabetes-related from unrelated IAA, but current assays do not distinguish between disease-predictive and non-predictive IAA or between IAA and insulin antibodies (IA). More recently, phage display technology has been successful in identifying disease-specific anti-idiotopes of insulin. In addition, phage display has facilitated the in vitro production of antibodies with high affinity. Identification of disease-specific anti-idiotopes of insulin should enable the production of a high affinity reagent against the same anti-idiotope. Such a development would form the basis of a disease-specific radioimmunoassay able to identify and measure particular idiotypes, rather than merely detect and titrate IAA.
Targeted deletion of Wwox reveals a tumor suppressor function (2007)

The WW domain-containing oxidoreductase (WWOX) spans the second most common fragile site of the human genome, FRA16D, located at 16q23, and its expression is altered in several types of human cancer. We have previously shown that restoration of WWOX expression in cancer cells suppresses tumorigenicity. To investigate WWOX tumor suppressor function in vivo, we generated mice carrying a targeted deletion of the Wwox gene and monitored incidence of tumor formation. Osteosarcomas in juvenile Wwox(-/-) and lung papillary carcinoma in adult Wwox(+/-) mice occurred spontaneously. In addition, Wwox(+/-) mice develop significantly more ethyl nitrosourea-induced lung tumors and lymphomas in comparison to wild-type littermate mice. Intriguingly, these tumors still express Wwox protein, suggesting haploinsuffiency of WWOX itself is cancer predisposing. These results indicate that WWOX is a bona fide tumor suppressor.
Amphiphilic networks. X. Diffusion of glucose and insulin (and nondiffusion of albumin) through amphiphilic membranes (1997)

Select semipermeable amphiphilic membranes have been prepared and their diffusional characteristics for glucose, insulin, and albumin investigated. The membranes were prepared by cast copolymerization of a hydrophilic monomer (i.e., N,N-dimethyl acrylamide, or N,N-dimethylaminoethyl methacrylate) with the hydrophobic crosslinker methacrylate-ditelechelic polyisobutylene. The products have sufficient mechanical properties for the fabrication of swollen membranes, sheets, tubes, etc. Membranes have been identified which allowed the rapid simultaneous countercurrent diffusion of glucose (Mn = 180 Da) and insulin (Mn = 5733 Da) but did not allow albumin (Mn approximately 60,000 Da) to pass. Evidently, the effective molecular weight cutoff point of these membranes is in the 6-60-KDa range.
Induced Differentiation of Human Myeloid Leukemia Cells into M2 Macrophages by Combined Treatment with Retinoic Acid and 1α,25-Dihydroxyvitamin D3 (2014)

Retinoids and 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) induce differentiation of myeloid leukemia cells into granulocyte and macrophage lineages, respectively. All-trans retinoic acid (ATRA), which is effective in the treatment of acute promyelocytic leukemia, can induce differentiation of other types of myeloid leukemia cells, and combined treatment with retinoid and 1,25(OH)2D3 effectively enhances the differentiation of leukemia cells into macrophage-like cells. Recent work has classified macrophages into M1 and M2 types. In this study, we investigated the effect of combined treatment with retinoid and 1,25(OH)2D3 on differentiation of myeloid leukemia THP-1 and HL60 cells. 9-cis Retinoic acid (9cRA) plus 1,25(OH)2D3 inhibited proliferation of THP-1 and HL60 cells and increased myeloid differentiation markers including nitroblue tetrazolium reducing activity and expression of CD14 and CD11b. ATRA and the synthetic retinoic acid receptor agonist Am80 exhibited similar effects in combination with 1,25(OH)2D3 but less effectively than 9cRA, while the retinoid X receptor agonist HX630 was not effective. 9cRA plus 1,25(OH)2D3 effectively increased expression of M2 macrophage marker genes, such as CD163, ARG1 and IL10, increased surface CD163 expression, and induced interleukin-10 secretion in myeloid leukemia cells, while 9cRA alone had weaker effects on these phenotypes and 1,25(OH)2D3 was not effective. Taken together, our results demonstrate selective induction of M2 macrophage markers in human myeloid leukemia cells by combined treatment with 9cRA and 1,25(OH)2D3.
Thioredoxin and thioredoxin reductase gene expression in human tumors and cell lines, and the effects of serum stimulation and hypoxia. (1997)

Thioredoxin and thioredoxin reductase are redox proteins that have been implicated in the control of cell proliferation and transformation. We report the levels and activity of these proteins and their mRNAs in human primary tumors and tumor cell lines. Half of human primary colorectal carcinomas (5/10) examined had increased thioredoxin mRNA, of 3- to over 100-fold, compared to adjacent normal colonic mucosa from the same subject. Thioredoxin reductase protein and activity were increased an average of 2-fold in human colorectal tumors compared to normal mucosa. A number of human hematologic and solid tumor cell lines were studied and showed a 10-fold range of thioredoxin mRNA and a 23-fold range of thioredoxin reductase mRNA. Increased proliferation and hypoxia are factors that might contribute to the increased expression in solid tumors. We found that serum stimulation of growth arrested MCF-7 breast cancer cells caused a 59% increase in thioredoxin mRNA and a 62% increase in thioredoxin reductase mRNA by 24 hours. Exposure of HT-20 colon cancer cells to hypoxia resulted in a 14-fold increase in thioredoxin mRNA by 16 hours, and a transient 4-fold increase in thioredoxin reductase mRNA at 1 hour that had returned to control levels by 8 hours. Cancer cells were found to release thioredoxin into the medium at rates between 1 to 2 pmole/10(6) cells/3 hours. The rate of secretion was not, however, related to cellular-levels of thioredoxin. The results of the study show that the expression of thioredoxin and thioredoxin reductase are increased several fold in some human solid tumors compared to normal tissue. Secretion of thioredoxin, which is known to have a direct growth stimulating activity, by human tumor cells might lead to the stimulation of cancer cell growth.
CD4 cells can be more efficient at tumor rejection than CD8 cells (2007)

Researchers designing antitumor treatments have long focused on eliciting tumor-specific CD8 cytotoxic T lymphocytes (CTL) because of their potent killing activity and their ability to reject transplanted organs. The resulting treatments, however, have generally been surprisingly poor at inducing complete tumor rejection, both in experimental models and in the clinic. Although a few scattered studies suggested that CD4 T "helper" cells might also serve as antitumor effectors, they have generally been studied mostly for their ability to enhance the activity of CTL. In this mouse study, we compared monoclonal populations of tumor-specific CD4 and CD8 T cells as effectors against several different tumors, and found that CD4 T cells eliminated tumors that were resistant to CD8-mediated rejection, even in cases where the tumors expressed major histocompatibility complex (MHC) class I molecules but not MHC class II. MHC class II expression on host tissues was critical, suggesting that the CD4 T cells act indirectly. Indeed, the CD4 T cells partnered with NK cells to obtain the maximal antitumor effect. These findings suggest that CD4 T cells can be powerful antitumor effector cells that can, in some cases, outperform CD8 T cells, which are the current "gold standard" effector cell in tumor immunotherapy.
The estimation and measurement of the efficiency and effectiveness of small antennas in an environment (2003)

A new Q-bandwidth measurement method for most small antennas allows all the significant radiation resistance and loss components affecting the antenna input impedance to be separated and measured. The various antenna efficiencies can be determined from measurements made at the antenna terminals. A new line-integral potential method is used. Better calibration of these will come both from interpreting existing results and from making further measurements to confirm or contradict past measurements.
Immunohistochemical analysis of neural cell adhesion molecules. Differential expression in small round cell tumors of childhood and adolescence. (1991)

The neural cell adhesion molecule (NCAM) was discovered in a search for cell surface antigens of chicken neurons that contribute to cell adhesion and pattern formation during development. Homologous adhesion molecules have been identified in several species, including humans. In this immunohistochemical study, the authors examine the role of human NCAM in tumor diagnosis. The authors used a monoclonal antibody (MAb), 5.1H11, to examine NCAM immunoreactivity in frozen sections of more than 450 tumors, including more than 80 small round cell tumors (SRCT) of childhood and adolescence (neuroblastomas, Ewing's sarcomas [ES], peripheral neuroepitheliomas [PN], primitive neuroectodermal tumors [PNET], esthesioneuroblastomas, malignant ectomesenchymoma, medulloblastomas, small cell osteosarcomas, mesenchymal chondrosarcomas, embryonal rhabdomyosarcomas, and lymphomas). The authors show that 1) neuroblastomas and primary brain tumors are NCAM+; 2) ES, most PN/PNETs, and melanomas are NCAM-; 3) embryonal rhabdomyosarcomas and various other sarcomas are NCAM+; 4) neuroendocrine tumors are NCAM+; 5) subsets of carcinomas of kidney, ovary, lung and other organs are NCAM+; and 6) lymphoid tumors are NCAM-. Tests with normal fetal and adult tissues indicate that these findings reflect only in part the NCAM phenotypes of corresponding normal tissues. Notably the NCAM- phenotype of ES and PN/PNET is not explained by current histogenetic models for these tumors, which suggest a primitive neuroectodermal origin. Finally the authors show that NCAM expression among SRCT has an inverse relationship with the expression of p30/32MIC2, a cell surface antigen of ES and PN/PNET detected with MAb HBA71. These results suggest that immunohistochemical assays for NCAM and p30/32MIC2 expression may aid in the further characterization of SRCT of childhood and adolescence.