gebhart/patrepeval huggingface dataset:
Increased prevalence and titer of Epstein‐Barr virus antibodies in patients with multiple sclerosis (1985)

The prevalence and titer of serum antibodies to several Epstein-Barr virus (EBV) antigens were compared among patients with multiple sclerosis, healthy siblings of multiple sclerosis patients, patients with other neurological diseases, and healthy non-blood-related subjects. Serum-cerebrospinal fluid (serum-CSF) pairs were available on a selected number of multiple sclerosis and control subjects. An increased antibody response to EBV antigens was noted rather consistently in the sera of the multiple sclerosis group in comparison with the control groups. A greater number of reduced ratios of serum:CSF IgG antibody to EBV-capsid antigen and antibody to EBV-early antigen components than to adenovirus, a reference or control virus, were found in the multiple sclerosis group. Reduced ratios of these EBV antibodies were detected more frequently or showed a trend in this direction in multiple sclerosis patients compared with the group with other neurological diseases. Our findings extend the results of an earlier report and strengthen the association between EBV and multiple sclerosis.
Pharmacokinetics of promethazine and its sulphoxide metabolite after intravenous and oral administration to man. (1983)

Blood concentrations of promethazine and promethazine sulphoxide have been measured following oral and intravenous administration of promethazine to seven healthy male volunteers. Promethazine disposition is characterised by a large volume of distribution (1970 1) and a high blood clearance (1.141 min-1). Less than 1% of the dose is excreted unchanged in the urine, therefore total body clearance is essentially metabolic clearance. In accord with this high clearance the oral availability of promethazine is only 25%. The absorption of promethazine from the gastrointestinal tract exceeds 80% in most subjects. Minimal metabolism by the gastrointestinal mucosa is implicated. Promethazine sulphoxide pharmacokinetics are consistent with a pronounced first pass effect. Although the area under the curve for this metabolite is not route dependent, there is a marked alteration in the shape of the metabolite curve when oral and intravenous data are compared. Evidence is presented to support the hypothesis that S-oxidation of promethazine is predominantly an hepatic event. The conclusions of previous investigators with regard to the role of the gut mucosa in S-oxidation of phenothiazines is critically assessed.
Oligonucleotide-Directed DNA Triple-Helix Formation: An Approach to Artificial Repressors? (1991)

Pyrimidine oligonucleotides exhibit sequence-specific binding to purine sequences in double-helical DNA. Molecular recognition occurs through triple-helix formation, mediated by Hoogsteen hydrogen bonding of the pyrimidine strand parallel to the double-helical DNA purine strand. Oligonucleotide-directed DNA triple-helix formation has been shown to inhibit the recognition of double-helical DNA by sequence-specific binding proteins. This observation provides the potential for new approaches to both the analysis of nucleic acids, and the study of nucleic acid-protein interactions. We wish to understand molecular mechanisms whereby such complexes affect protein-DNA interactions involved in eukaryotic transcription.
Synthesis of Rubrivivax gelatinosus Lipid A and Analogues for Investigation of the Structural Basis for Immunostimulating and Inhibitory Activities (2008)

Abstract To elucidate the structural requirements for the endotoxic and antagonistic activities of lipid A derivatives, we have focused on the effects of the acyl moieties and acidic groups at the 1- and 4′-positions in the present study. We have synthesized new analogues corresponding to Rubrivivax gelatinosus lipid A, which has a characteristic symmetrical distribution of its acyl groups on its two glucosamine residues with shorter acyl groups (decanoyl groups (C10) and lauryl groups (C12)) than Escherichia coli lipid A’s. Carboxymethyl (CM) analogues in which one of the phosphates was replaced with a CM group were also synthesized with a different distribution of acyl groups. Biological tests revealed that the acyl group distribution in the lipid A analogue, strongly affected its bioactivity. The synthetic Ru. gelatinosus type lipid A showed potent antagonistic activity against LPS, whereas its 1-O-carboxymethyl analogue showed weak endotoxic activity. These results demonstrate that when lipid A has shorter (C10 and C12) hexa-acyl groups, its bioactivity is more easily affected by small structural differences, such as differences in acidic groups or acyl group distribution, and that they can change bioactivity from endotoxic to agonistic or vice versa at this structural boundary for the bioactivity.
Fully automatic determination of soil bacterium numbers, cell volumes, and frequencies of dividing cells by confocal laser scanning microscopy and image analysis (1995)

We describe a fully automatic image analysis system capable of measuring cell numbers, volumes, lengths, and widths of bacteria in soil smears. The system also determines the number of cells in agglomerates and thus provides the frequency of dividing cells (FDC). Images are acquired from a confocal laser scanning microscope. The grey images are smoothed by convolution and by morphological erosion and dilation to remove noise. The background is equalized by flooding holes in the image and is then subtracted by two top hat transforms. Finally, the grey image is sharpened by delineation, and all particles above a fixed threshold are detected. The number of cells in each detected particle is determined by counting the number of local grey-level maxima in the particle. Thus, up to 1,500 cells in 10 fields of view in a soil smear are analyzed in 30 min without human intervention. Automatic counts of cell numbers and FDC were similar to visual counts in field samples. In microcosms, automatic measurements showed significant increases in cell numbers, FDC, mean cell volume, and length-to-width ratio after amendment of the soil. Volumes of fluorescent microspheres were measured with good approximation, but the absolute values obtained were strongly affected by the settings of the detector sensitivity. Independent measurements of bacterial cell numbers and volumes by image analysis and of cell carbon by a total organic carbon analyzer yielded an average specific carbon content of 200 fg of C (mu)m(sup-3), which indicates that our volume estimates are reasonable.
Infant mortality and congenital anomalies from 1950 to 1994: an international perspective (2000)

Congenital malformations account for an increasing proportion of infant deaths in both developed and developing countries. Infant mortality attributable to congenital anomalies is higher in poorer countries although as a proportion of infant deaths it is greater in wealthier countries. Conditions such as spina bifida, whose occurrence can be reduced through preventive strategies, still cause many infant deaths. The apparent increase of infant mortality because of congenital anomalies in some countries should be investigated to confirm the finding, find the causes, and provide prevention opportunities.
THIOLATION OF PROTEINS (1958)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
A Comparison of Prognostic Factors and Surgical Results in 1,786 Patients with Localized (Stage I) Melanoma Treated in Alabama, USA, and New South Wales, Australia (1982)

Twelve clinical and pathologic parameters were compared in two series of Stage I melanoma patients treated at the University of Alabama in Birmingham, USA (676 patients) and at the University of Sydney in New South Wales, Australia (1,110 patients). Actuarial survival rates were virtually the same at the two institutions over a 25-year follow-up period. The incidence of thin melanomas (less than 0.76 mm) was also similar at both geographic locations (25% vs. 26%). Other similarities of these two patient populations included the following: 1) tumor thickness (Breslow Microstaging). 2) level of invasion (Clark Microstaging), 3) surgical results, 4) sex distribution, and 5) age distribution. The greatest differences between the two patient populations were their 1) anatomic distribution, 2) growth pattern, and 3) incidence of ulceration. The trunk was the most common site of melanoma, and occurred more frequently among Australian patients (37% vs. 28%). A multifactorial analysis (Cox's regression model) was then performed that included a comparison of the two institutions as a variable (Alabama vs. Australia). The dominant prognostic factors (p less than 0.0001) were 1) ulceration, 2) tumor thickness, 3) initial surgical management (wide excision +/- node dissection), 4) anatomic location, 5) pathologic stage (I vs. II), and 6) level of invasion. The benefit of elective lymph node dissection was demonstrated in both series for patients with intermediate thickness melanoma (0.76 to 3.99 mm.) For melanomas ranging from 0.76 to 1.5 mm in thickness, the benefit of node dissection was primarily in male patients. Survival rates for melanoma at the two institutions were not significantly different in the multifactorial analysis, even after adjusting for all other variable. Thus, the biologic behavior of melanoma in these two different parts of the world was virtually the same, with only minor differences that did not significantly influence survival rates. Long-term follow-up exceeding eight to ten years after surgery is critical in the interpretation of these prognostic factors and the surgical results.
A Human ErbB2-Specific T-Cell Receptor Confers Potent Antitumor Effector Functions in Genetically Engineered Primary Cytotoxic Lymphocytes (2014)

The ErbB2 protein is a member of the tyrosine kinase family of growth factor receptors that is overexpressed in cancers of the breast, ovary, stomach, kidney, colon, and lung, and therefore represents an attractive candidate antigen for targeted cancer immunotherapy. Cytotoxic T lymphocytes specific for various immunogenic ErbB2 peptides have been described, but they often exhibit both poor functional avidity and tumor reactivity. In order to generate potent CD8(+) T cells with specificity for the ErbB2(369-377) peptide, we performed one round of in vitro peptide stimulation of CD8(+) T cells isolated from an HLA-A2(+) patient who was previously vaccinated with autologous dendritic cells pulsed with HLA class I ErbB2 peptides. Using this approach, we enriched highly avid ErbB2-reactive T cells with strong ErbB2-specific, antitumor effector functions. We then stimulated these ErbB2-reactive T cells with ErbB2(+) HLA-A2(+) tumor cells in vitro and sorted tumor-activated ErbB2(369-377) peptide T cells, which allowed for the isolation of a novel T-cell receptor (TCR) with ErbB2(369-377) peptide specificity. Primary human CD8(+) T cells genetically modified to express this ErbB2-specific TCR specifically bound ErbB2(369-377) peptide containing HLA-A2 tetramers, and efficiently recognized target cells pulsed with low nanomolar concentrations of ErbB2(369-377) peptide as well as nonpulsed ErbB2(+) HLA-A2(+) tumor cell lines in vitro. In a novel xenograft model, ErbB2-redirected T cells also significantly delayed progression of ErbB2(+) HLA-A2(+) human tumor in vivo. Together, these results support the notion that redirection of normal T-cell specificity by TCR gene transfer can have potential applications in the adoptive immunotherapy of ErbB2-expressing malignancies.
Transient temperature rise due to ultrasound absorption at a bone/soft-tissue interface (2004)

Thermal effects due to high ultrasound absorption in bone pose an ongoing safety issue. Of considerable concern is the heating of the soft tissue adjacent to the bone surface. Mathematical models can be useful in predicting the transient temperature near the interface during insonation. This paper develops a model that provides the temperature field in terms of simple expressions that convey the functional dependence of the material properties, and are easily incorporated into standards and ultrasound machine software, yet are able to incorporate the material properties of both bone and soft tissue. The model contains an asymptotic theory based upon a "high-attenuation" assumption: the distance diffused by heat over the time of interest is large compared to the ultrasound attenuation length. Model predictions of temperature rise and location of maximum temperature were in close agreement with finite-element calculations, using parameters appropriate for radiation-force imaging and focused-ultrasound surgery.
Some sample programs written in DryadLINQ (2009)

Preoperative thrombocytopenia had an undesirable impact on the recurrence of small HCC patients treated with liver resection.
Organic Synthesis by Catalysis with Ion-Exchange Resins (2005)

This review is intended to give a wide scope on the uses of ion-exchange resins as catalysts or catalyst precursors in organic synthesis, for the preparation of fine or intermediate chemicals. Twelve families of reaction have been covered and presented according to the molecules to be synthesized, regardless of the anionic or cationic nature of the resins; thus, ∼300 references have been selected from January 1980. In acid-catalyzed reactions, the contribution of both Lewis acidity and Brönsted acidity are mentioned, and, when available, some aspects related to the stability or the recycling of the catalysts are reported. In base-catalyzed reactions, the importance of the thermal stability of anionic resins has been underlined. A table that is included as an appendix provides some data on the resins quoted here.
Expression of activated and latent signal transducer and activator of transcription 3 in 303 non-small cell lung carcinomas and 44 malignant mesotheliomas: possible role for chemotherapeutic intervention. (2007)

The strong expression of cytoplasmic inactive STAT3 in NSCLC and MM cases implies a major role for STAT3 in tumor motility, invasion, and metastasis via a nontranscriptional pathway. We conclude that STAT3 and pSTAT3 are up-regulated in a high percentage of NSCLCs and MMs, regardless of tumor type, age, sex, smoking status, stage and grade of tumor, or survival, providing a basis for therapeutic intervention.
The role of human immunodeficiency virus-I in the pathogenesis of acquired immunodeficiency syndrome-related Kaposi's sarcoma: the importance of an inflammatory and angiogenic milieu. (2000)

People infected with human immunodeficiency virus type-I (HIV-I) have an increased incidence of Kaposi's sarcoma (KS) and HIV-I infection alters the natural history of KS. The potent trans-activator HIV-I protein Tat plays a major role in the pathogenesis of acquired immunodeficiency syndrome (AIDS)-related KS. Among many of its KS-promoting activities, the Tat protein augments the angiogenic activities of basic fibroblast growth factor (bFGF), interferon gamma, and vascular endothelial growth factor (VEGF); it also mimics the effects of the extramedullary matrix proteins fibronectin and vitronectin, and increases the expression of matrix metalloproteinases. Inflammatory cytokines induce endothelial cells to acquire the phenotype and functional features of AIDS-related KS spindle cells. These cytokines act by both autocrine and paracrine mechanisms. The synergy between cytokines and the HIV-I Tat protein provides possible insight into why AIDS-related KS is more aggressive than the classic Mediterranean form, in which the HIV-I Tat protein does not play a role.
Normal cations and abnormal membrane lipids in the red blood cells of dogs with familial stomatocytosis-hypertrophic gastritis (1994)

Abstract Examination of the red blood cells (RBCs) of eight dogs with familial stomatocytosis-hypertrophic gastritis (FS-HG), a multiorgan disease associated with hemolytic anemia, hereditary stomatocytosis (HSt), and hypertrophic gastritis resembling Menetrier's disease in man, showed abnormal osmotic fragility, normal mean corpuscular volume, slightly increased cell water, and normal cation content and cation fluxes. Cholesterol was decreased in RBC and increased in plasma. In both RBCs and plasma, total phospholipid (PL) was normal, phosphatidylcholine (PC) decreased, and sphingomyelin increased. The palmitic acid content of PC was increased, and the stearic acid content of PC was decreased. Sodium dodecyl sulfate electrophoresis of RBC membrane proteins was normal. These findings have not been described previously in HSt. They suggest that in FS-HG, abnormal composition of the PL in RBCs secondary to abnormal PL in plasma causes defective membrane function and stomatocytic shape-change. This conclusion was supported by a shortened half-life of 51Cr-labeled RBCs from normal dogs after transfusion in dogs with FS-HG. It was concluded (1) that not all hereditary forms of stomatocytosis are necessarily associated with an intrinsic structural defect of the RBC membrane, but that the change in shape of RBC may also be induced by abnormal composition of the plasma; (2) that stomatocytosis may be caused by loss of membrane surface area rather than by the increased cation uptake such as has been shown in some human kindreds with HSt, (3) that FS-HG is a disorder of lipid metabolism, and by consequence, (4) that abnormal lipid metabolism might be involved in the pathogenesis of Menetrier's disease.
Cascade transactivation of growth factor receptors in early human hematopoiesis (1993)

Highly purified progenitors (including erythroid [BFU-E], granulo-monocytic [CFU-GM], multipotent [CFU-GEMM] progenitors, as well as multipotent progenitors with self-renewal capacity [CFU-B]) express high-affinity growth factor receptors (GFRs), with prevalent interleukin-3 receptors (IL-3Rs) (2,700/cell), a > or = 10-fold lower number of IL-6Rs (145/cell) and granulocyte-macrophage colony-stimulating factor receptors (GM-CSFRs) (300/cell), and a barely detectable level of erythropoietin (Ep) receptors (75/cell). Hematopoietic growth factor (HGF) dosages inducing peak clonogenetic effects are associated with partial/subtotal occupancy of the homologous HGF receptor (HGFR). Cross-reactivity between GFRs and heterologous GFs (including IL-6, IL-3, GM-CSF, Ep, and the kit ligand [KL]) was explored by competition experiments on purified progenitors with radiolabeled and excess cold HGFs at +4 degrees C. No cross-reaction was observed between IL-6R, IL-3R, EpR, and the heterologous GFs, whereas the GM-CSFR showed cross-reactivity with IL-3 and, to a lesser extent, KL. Modulation of GFRs was examined after 18 or 40 hours of incubation with GF(s) at 37 degrees C, followed by ligand-binding assay at 20 degrees C. IL-6, IL-3, GM-CSF, and Ep induce a marked down-modulation of their own receptors. Interestingly, each GF induces the transactivation of the R(s) for the "distal" GF(s): (1) IL-6 induces transactivation of IL-3R, but not of GM-CSFR/EpR; (2) IL-3 causes a rapid upmodulation of GM-CSFR/EpR ("pure" progenitors treated with IL-3 show upmodulation of GM-CSFR alpha-chain mRNA by reverse transcriptase-polymerase chain reaction); whereas (3) GM-CSF induces the transactivation of the EpR. This chain upmodulation of HGFRs may underlie the synergistic interactions between the HGFs in clonogenetic culture. It is emphasized that KL does not induce upmodulation of the other GFRs. Finally, Ep, GM-CSF, and IL-3 do not modulate the expression of the "proximal" HGFRs (ie, GM-CSFR/IL-3R/IL-6R, IL-3R/IL-6R, and IL-6R, respectively). These results allow insight into the cellular basis of hematopoiesis, ie, the complex and coordinate interactions between HGFs and their receptors. They are compatible with a model of cascade transactivation via upmodulation of GFRs in the initial key steps of hematopoietic differentiation, whereby the action of each GF enhances the effect of the distal GF(s) by a multistep chain-potentiation mechanism.
The effects of β-glucan on human immune and cancer cells (2009)

Non-prescriptional use of medicinal herbs among cancer patients is common around the world. The alleged anti-cancer effects of most herbal extracts are mainly based on studies derived from in vitro or in vivo animal experiments. The current information suggests that these herbal extracts exert their biological effect either through cytotoxic or immunomodulatory mechanisms. One of the active compounds responsible for the immune effects of herbal products is in the form of complex polysaccharides known as beta-glucans. beta-glucans are ubiquitously found in both bacterial or fungal cell walls and have been implicated in the initiation of anti-microbial immune response. Based on in vitro studies, beta-glucans act on several immune receptors including Dectin-1, complement receptor (CR3) and TLR-2/6 and trigger a group of immune cells including macrophages, neutrophils, monocytes, natural killer cells and dendritic cells. As a consequence, both innate and adaptive response can be modulated by beta-glucans and they can also enhance opsonic and non-opsonic phagocytosis. In animal studies, after oral administration, the specific backbone 1-->3 linear beta-glycosidic chain of beta-glucans cannot be digested. Most beta-glucans enter the proximal small intestine and some are captured by the macrophages. They are internalized and fragmented within the cells, then transported by the macrophages to the marrow and endothelial reticular system. The small beta-glucans fragments are eventually released by the macrophages and taken up by other immune cells leading to various immune responses. However, beta-glucans of different sizes and branching patterns may have significantly variable immune potency. Careful selection of appropriate beta-glucans is essential if we wish to investigate the effects of beta-glucans clinically. So far, no good quality clinical trial data is available on assessing the effectiveness of purified beta-glucans among cancer patients. Future effort should direct at performing well-designed clinical trials to verify the actual clinical efficacy of beta-glucans or beta-glucans containing compounds.
Natural autoantibodies to interferons. (1997)

Natural antibodies that appear to have arisen in the absence of direct antigenic stimulation often are present in the circulation. In healthy individuals, they are of low prevalence and generally show low affinity to their respective antigens, whereas in autoimmune disease, their frequency and affinity toward specific antigens are in many cases increased. In some autoimmune disease, the spontaneous occurrence of autoantibodies to antigens that are apparently unrelated to symptoms or pathology has been observed. For example, antibodies to interferon-alpha (IFN-alpha) have been observed in patients with systemic lupus erythematosus but appear to be of no clinical significance. Natural autoantibodies to IFN-alpha have also been found in other patients, including those with insulin-dependent diabetes mellitus, heart disease, or cancer and patients who have just received allogeneic bone marrow transplantation. A major property of IFN-alpha autoantibodies is their capacity to both bind to and neutralize the biologic activity of a range of IFN-alpha subtypes and natural IFN-alpha preparations. Their origins and significance remain a matter for debate.