gebhart/patrepeval huggingface dataset:
Raised serum levels of interleukin-18 is associated with disease progression and may contribute to virological treatment failure in HIV-1-infected patients (2003)

To gain further insight into the possible role of interleukin (IL)-18 in HIV-1 infection we examined serum levels of IL-18 in various clinical and immunological stages of HIV-1 infection during cross-sectional (n = 41) and longitudinal testing (n = 20) and during HAART (n = 21, 24 months follow-up). Our main findings were that HIV-1-infected patients had significantly raised IL-18 levels comparing healthy controls, particularly in those with advanced disease, that while HAART induced a marked decline in IL-18, virological treatment failure was associated with persistently raised IL-18 levels during such therapy and that our in vitro experiments showed an IL-18-mediated up-regulation of the HIV-1 coreceptor CXCR4 and the pro-apoptotic mediator TRAIL in PBMC from HIV-1-infected patients receiving HAART. HIV-1 infection appears to be characterized by persistently raised IL-18 levels and during HAART, such a pattern was associated with virological treatment failure, possibly contributing to immunodeficiency and HIV-1 replication in these patients.
Definition of tumor antigens suitable for vaccine construction (1995)

The treatment of cancer with tumor vaccines has been a goal of physicians and scientists ever since effective immunization against infectious disease with vaccines was developed. In the past, major tumor antigens had not been molecularly characterized. Recent advances are, however, beginning to define potential molecular targets and strategies and this had evolved with the principle that T-cell mediated responses are a key target for approaches to cancer immunization. In addition, these antigens are not truly foreign and tumour antigens fit more with a self/altered self paradigm, compared to a non-self paradigm for antigens recognized in infectious diseases. Potential antigens include the glycolipids and glycoproteins (e.g. gangliosides), the developmental antigens (e.g. MAGE, tyrosinase, melan-A and gp75) and mutant oncogene products (e.g. p53, ras, and HER-2/neu). Innovations for construction of cancer vaccines are emerging from these advances in molecular immunology and cancer biology. While vaccines against infectious agents are models for vaccine development, there are clearly distinct considerations and problems associated with cancer vaccines. One of the focal issues in designing active cancer immunotherapy is that cancer cells are derived from normal host cells. Thus, the antigenic profile of cancer cells closely mimics that of normal cells. How the immune system identifies and destroys cancer cells is therefore crucial. Clearly, the ultimate goal of tumor vaccine design is the generation of antigen-specific vaccines. The recent success identifying molecularly defined tumor antigens opens up potentially novel strategies for this approach. Vaccine possibilities include purified proteins and glycolipids, peptides, cDNA expressed in various vectors, and a range of immune adjuvants. The molecular and structural definition of tumor antigens provides an opportunity for cautious optimism that we are entering an era when we will soon begin to recapitulate the success of immunization against infectious disease.
Comparison of approaches to continuous hand gesture recognition for a visual dialog system (1999)

Continuous hand gesture recognition requires the detection of gestures in a video stream and their classification. In this paper two continuous recognition solutions using hidden Markov models (HMMs) are compared. The first approach uses a motion detection algorithm to isolate gesture candidates followed by a HMM recognition step. The second approach is a single-stage, HMM-based spotting method improved by a new implicit duration modeling. Both strategies have been tested on continuous video data containing 41 different types of gestures embedded in random motion. The data has been derived from usability experiments with an application providing a realistic visual dialog scenario. The results show that the improved spotting method in contrast to the motion detection approach can successfully suppress random motion providing excellent recognition results.
Glomerular epithelial cells in the urine: what has to be done to make them worthwhile? (2008)

The significance of the native urine sediment in the differential of glomerular diseases needs no further comment. However, the question arises whether it could be useful to develop a more specific diagnostic approach to identify the origin of renal epithelial cells that can be detected in the urine sediments as well. Especially the detection of podocytes in the urine could be a valuable noninvasive method to get information about the disease activity or disease type and could be used as a follow-up after a biopsy in an outpatient setting. So far, there are only a few studies that analyzed the clinical relevance of renal epithelial cells in the urine systematically or prospectively. The reason for this could be the nature of the material since it will remain unclear whether detachment and changes in the urine milieu have a direct effect on the expression of marker proteins on the detected cells. Dedifferentiation or transdifferentiation of cells that goes along with changed marker expression is certainly also part of the underlying disease process. This review summarizes the available information on marker proteins that have been successfully used in the diagnostic of "podocytes" in the urine. Furthermore, it gives an overview of marker expression on podocytes in situ in development and disease and examines the role of glomerular epithelial shedding in the urine at the interface of basic science and clinical medicine.
Endothelial-leukocyte adhesion molecule-1-dependent and leukocyte (CD11/CD18)-dependent mechanisms contribute to polymorphonuclear leukocyte adhesion to cytokine-activated human vascular endothelium. (1989)

We have examined the contributions of endothelial-leukocyte adhesion molecule-1 (ELAM-1) and the complex of leukocyte surface adhesion molecules designated CD11/CD18 to the adhesion of human polymorphonuclear leukocytes (PMN) to cultured human endothelial cells (HEC), activated by rIL-1 beta for 4 or 24 h. Inhibition of PMN attachment to IL-1-activated HEC was measured in a quantitative in vitro monolayer adhesion assay, after treatment with mAb directed to ELAM-1 (mAb H18/17), and to CD11a (mAb L11), CD11b (mAb 44), CD11c (mAb L29), and CD18 (mAb 10F12), alone or in combination. Pretreatment of activated HEC with mAb H18/7 inhibited PMN adhesion by 47 +/- 8% whereas control mAb had no effect. CD11/CD18-directed mAb significantly blocked PMN adhesion to activated HEC (anti-CD11a, 40 +/- 3%; anti-CD11b, 34 +/- 4%; anti-CD18, 78+/- 6% inhibition). The combination of mAb H18/7 and each of the various anti-CD11/CD18 mAb resulted in greater inhibition of PMN adhesion than any Mab alone. After 24 h of rIL-1 beta treatment, when ELAM-1 was markedly decreased but elevated PMN adhesion was still observed, mAb H18/7 had no effect on PMN adhesion. At this time, CD11/CD18-dependent adhesive mechanisms predominated and a CD11c-dependent mechanism became apparent (anti-CD11a, 67 +/- 4% inhibition; anti-CD11b, 45 +/- 9%; anti-CD11c, 26 +/- 6%; anti-CD18, 97 +/- 1%). In summary, PMN adhesion to IL-1-activated HEC involves both CD11/CD18-dependent mechanisms and an ELAM-1-dependent mechanism, and the relative contribution of these varies at different times of IL-1-induced HEC activation. The additive blocking observed at 4 h with mAb H18/7 in combination with CD11/CD18-directed Mab implies that members of the CD11/CD18 complex do not function as an obligate ligand(s) for ELAM-1.
Minimization by Random Search Techniques (1981)

We give two general convergence proofs for random search algorithms. We review the literature and show how our results extend those available for specific variants of the conceptual algorithm studied here. We then exploit the convergence results to examine convergence rates and to actually design implementable methods. Finally we report on some computational experience.
Enhanced erythropoiesis in Hfe-KO mice indicates a role for Hfe in the modulation of erythroid iron homeostasis (2010)

In hereditary hemochromatosis, mutations in HFE lead to iron overload through abnormally low levels of hepcidin. In addition, HFE potentially modulates cellular iron uptake by interacting with transferrin receptor, a crucial protein during erythropoiesis. However, the role of HFE in this process was never explored. We hypothesize that HFE modulates erythropoiesis by affecting dietary iron absorption and erythroid iron intake. To investigate this, we used Hfe-KO mice in conditions of altered dietary iron and erythropoiesis. We show that Hfe-KO mice can overcome phlebotomy-induced anemia more rapidly than wild-type mice (even when iron loaded). Second, we evaluated mice combining the hemochromatosis and β-thalassemia phenotypes. Our results suggest that lack of Hfe is advantageous in conditions of increased erythropoietic activity because of augmented iron mobilization driven by deficient hepcidin response. Lastly, we demonstrate that Hfe is expressed in erythroid cells and impairs iron uptake, whereas its absence exclusively from the hematopoietic compartment is sufficient to accelerate recovery from phlebotomy. In summary, we demonstrate that Hfe influences erythropoiesis by 2 distinct mechanisms: limiting hepcidin expression under conditions of simultaneous iron overload and stress erythropoiesis, and impairing transferrin-bound iron uptake by erythroid cells. Moreover, our results provide novel suggestions to improve the treatment of hemochromatosis.
Adhesion molecule expression in acute and fibrotic sympathetic ophthalmia (1993)

Samples of iris ciliary body, choroid and retina from normal eyes and from 2 cases of sympathetic ophthalmitis (one acute and one late stage fibrosis) were examined for the expression of the VLA integrins beta 1 and alpha 1-6, and the integrin beta 3, in addition to ICAM-1, VCAM-1, ELAM-1 and CD44 using an APAAP staining technique. The expression of VLA-4, VLA-5, VCAM-1, ICAM-1, and CD44 was significantly increased and ELAM-1 was slightly increased in acute sympathetic ophthalmitis in comparison to fibrotic and normal eyes. VLA-6 was moderately increased in acute and fibrotic cases and VLA-2 VLA-3 and beta 3 were moderately expressed on all tissues examined. The differential expression of molecules known to be involved in lymphocyte activation and adhesion in acute sympathetic ophthalmitis suggests that certain adhesion molecules play a role in the pathogenesis of intraocular inflammation and may be suitable targets for immunotherapy.
Role of Metallothionein in Detoxification and Tolerance to Transition Metals (1987)

Animal tolerance to the transition metals cadmium and zinc is hereditary. The evolution to a high level of resistance can be accelerated through mutation and selective pressure. We have studied inbred strains of mice and mutants of Chinese hamster ovary cells resistant to cadmium to further these understandings. Results with whole animals show that the difference in the rate and level of metallothionein accumulation is at most twofold between sensitive and resistant strains. However, with cadmium resistant CHO mutant cells, there is an over 60 fold increase in metallothionein and its mRNA upon induction. These mutants show over 60 fold amplification in metallothionein genes. These results offer a direct contrast in the correlation between elevation of metal resistance and increases in metallothionein between two genetic systems.
Noninvasive Glucose Monitoring: A Novel Approach (2009)

Integrating several modalities for NI assessment of glucose level enables more accurate readings, while a possible aberration in one modality is bypassed by the others. The present generation of GlucoTrack gives promising results; however, further improvement of the accuracy of the device is needed.
Recent Advances in Chronic Granulomatous Disease (1983)

Chronic granulomatous disease represents a group of disorders of phagocytic cell oxidative metabolism involving recurrent infections with catalase-positive microorganisms and chronic inflammation. Genetic heterogeneity and phagocyte abnormalities, including enzyme deficiencies, abnormal elicited membrane potential changes, abnormal acidification of the phagocytic vacuole, and deficiencies of an electron transport cascade, have been associated with its pathogenesis. In addition, recently we have shown abnormal neutrophil C3b-receptor expression, antibody-dependent cellular cytotoxicity, and abnormal microtubule metabolism (tyrosinolation of the alpha-chain of tubulin). Fourteen patients with the disease who were followed at the National Institutes of Health had life-threatening infections, on average, once every 9.6 months. In most of the 119 febrile episodes seen in these patients, no infectious agent was found. Retrospective studies indicated that prophylactic antibiotic therapy, particularly with trimethoprim-sulfamethoxazole, significantly prolonged disease-free intervals to greater than 40 months (p less than 0.05). In serious, life-threatening infections, leukocyte transfusions have been used in therapy. Transfused leukocytes localize and persist at infectious sites, and the clinical efficacy of leukocyte transfusions has been suggested.
Evidence that Endometriosis Behaves in a Malignant Manner (2000)

It is well known that certain aspects of endometriosis are similar to those of malignant disease. For example, like cancer, endometriosis can be both locally and distantly metastatic; it attaches to other tissues, invades, and damages them. Endometriosis is a common disease that does not create a cachectic or catabolic state, and is rarely fatal. There are, however, numerous reported cases of malignancy arising from endometriotic deposits and substantial histologic evidence that endometriosis is associated with endometrioid carcinoma and clear cell carcinoma of the ovary. A large review article by Mostoufizadeh and Scully investigated the association between endometriosis and endometrioid carcinoma, noting that women who had both diseases tended to be younger [1]. They found no association between endometriosis and serous or mucinous carcinoma of the ovary, and reported that malignant transformation of endometriosis was rare and associated with the use of exogenous estrogens. An epidemiological study of Swedish women reported a higher incidence of breast and ovarian cancer and non-Hodgkin's lymphoma in women with endometriosis compared with controls [2]. Vercellini and colleagues also reported a higher incidence of endometrioid and clear cell carcinoma in women with endometriosis compared with controls [3]. Mutations in genes associated with galactose metabolism have been identified as one possible mechanism for this association. These mutations are more common in ovarian cancer and have been reported to be more common in women with endometriosis. We compared 78 women with endometriosis with 248 controls and were unable to demonstrate an increased frequency of these mutations in any of these groups.
Megakaryocytic Potentiating Factor and Mature Mesothelin Stimulate the Growth of a Lung Cancer Cell Line in the Peritoneal Cavity of Mice (2014)

The mesothelin (MSLN) gene encodes a 71 kilodalton (kDa) precursor protein that is processed into megakaryocytic potentiating factor (MPF), a 31 kDa protein that is secreted from the cell, and mature mesothelin (mMSLN), a 40 kDa cell surface protein. The mMSLN binds to CA125, an interaction that has been implicated in the intra-cavitary spread of mesothelioma and ovarian cancer. To better define the role of MPF and mMSLN, growth of the lung cancer cell line A549 was evaluated in immuno-deficient mice with inactivation of the Msln gene. We observed that Msln-/- mice xenografted with intraperitoneal A549 tumors survive significantly long than tumor-bearing Msln+/+ mice. When tumor-bearing Msln-/- mice are supplemented with recombinant MPF (and to a lesser extent mMSLN), most of this survival advantage is lost. These studies demonstrate that MPF and mMSLN have an important role in the growth of lung cancer cells in vivo and raise the possibility that inactivation of MPF may be a useful treatment for lung and other MSLN expressing cancers.
Neuronal production, migration, and differentiation in a vocal control nucleus of the adult female canary brain. (1983)

The vocal control nucleus designated HVc (hyperstriatum ventrale, pars caudalis) of adult female canaries expands in response to systemic testosterone administration, which also induces the females to sing in a male-like manner. We became interested in the possibility of neurogenesis as a potential basis for this phenomenon. Intact adult female canaries were injected with [3H]thymidine over a 2-day period. Some birds were given testosterone implants at various times before thymidine. The birds were sacrificed 5 wk after hormone implantation, and their brains were processed for autoradiography. In parallel control experiments, some birds were given implants of cholesterol instead of testosterone. All birds showed considerable numbers of labeled neurons, glia, endothelia, and ventricular zone cells in and around HVc. Ultrastructural analysis confirmed the identity of these labeled neurons. Cholesterol- and testosterone-treated birds had similar neuronal labeling indices, which ranged from 1.8% to 4.0% in HVc. Thus, neurogenesis occurred in these adults independently of exogenous hormone treatment. Conversely, both glial and endothelial proliferation rates were markedly stimulated by exogenous testosterone treatment. We determined the origin of the thymidine-incorporating neurons by sacrificing two thymidine-treated females soon after their thymidine injections, precluding any significant migration of newly labeled cells. Analysis of these brains revealed no cells of neuronal morphology present in HVc but a very heavily labeled ventricular zone overlying HVc. We conclude that neuronal precursors exist in the HVc ventricular zone that incorporate tritiated thymidine during the S phase preceding their mitosis; after division these cells migrate into, and to some extent beyond, HVc. This ventricular zone neurogenesis seems to be a normally occurring phenomenon in intact adult female canaries.
High-Sensitivity Capillary Electrophoresis of Double-Stranded DNA Fragments Using Monomeric and Dimeric Fluorescent Intercalating Dyes (1994)

Fluorescence-detected capillary electrophoresis separations of phi X174/HaeIII DNA restriction fragments have been performed using monomeric and dimeric intercalating dyes. Replaceable hydroxyethyl cellulose solutions were used as the separation medium. Confocal fluorescence detection was performed following 488-nm laser excitation. The limits of DNA detection for on-column staining with monomeric dyes (ethidium bromide, two propidium dye derivatives, oxazole yellow, thiazole orange, and a polycationic thiazole orange derivative) were determined. The thiazole orange dyes provide the most sensitive detection with limiting sensitivities of 2-4 amol of DNA base pairs per band, and detection of the 603-bp fragment was successful, injecting from phi X174/HaeIII samples containing only 1-2 fg of this fragment per microliter. Separations of preformed DNA-dimeric dye complexes were also performed. The breadth of the bands observed in separations of preformed DNA-dimeric dye complexes is due to the presence of DNA fragments with different numbers of bound dye molecules that can be resolved as closely spaced subbands in many of our separations. The quality of these DNA-dye complex separations can be dramatically improved by performing the electrophoresis with 9-aminoacridine (9AA) in the column and running buffers. The optimum concentrations of 9AA for the separation of complexes preformed with the dimeric dyes TOTO, EthD, TOTAB, and YOYO were determined to be 100, 1, 1, and 0.5 microM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
A practical space-frequency block coded OFDM scheme for fast fading broadband channels (2003)

Multi-antenna OFDM system calls the consideration of coding across antennas and OFDM tones. Derived from the design criteria for space-time block codes (STBC), the coding scheme termed space-frequency block codes (SFBC) is conceived to achieve the maximum diversity order for a given number of transmit and receive antennas. In this contribution, a practical space-frequency block coded OFDM scheme (SFBC-OFDM) is proposed for fast fading broadband channels. Besides, this novel scheme is rather flexible to combat the frequency-selective fading by decreasing the coding size. Simulation and analysis show that our scheme outperforms the STBC-OFDM scheme in the scenario with high vehicle speed and large delay spread when the number of subcarriers in the OFDM system is large.
A phase II open-label study of OSI-774 (NSC 718781) in unresectable hepatocellular carcinoma (2005)

4038 Background: Hepatocellular carcinoma (HCC) is the 4th most common cancer worldwide and is increasing in the United States and other western countries. HCC are chemotherapy-resistant tumors, and current systemic therapy has been unable to prolong survival. Epidermal growth factor receptor (EGFR) is overexpressed in a majority of HCC, thus it is rational to study OSI-774, a small molecule EGFR tyrosine kinase inhibitor, in this disease. Patients and Methods: Prospective Phase II study of OSI-774 in pts with previously untreated advanced HCC. A total of 25 patients (pts) have been enrolled to date. Patients accrue to 1 of 2 strata based on low (0–2+; 6 pts, 24%) or high (3–4+; 19 pts, 76%) tumor EGFR expression by immunohistochemistry (IHC). The primary endpoint is the rate of progression-free survival at 16 weeks of OSI-774 treatment. All patients received OSI-774 at 150 mg/po daily. Demographics: male 19, female 6, median age 66, cirrhosis 12 pts, no cirrhosis 13 pts, Childs-Pugh class A, 25 pts (100%); ECOG 0, 8 pts (32%); 1, 14 pts (56%); 2, 3 pts (12%); risk factors hepatitis C virus (HCV) 9 (36%), HBV 4 pts; other 12 (48%). Functional computed tomography (fCT) scans were performed on all pts at baseline, 4, 12, and 16 wks, to evaluate whether OSI-774 changed tumor blood flow. Results: 8 pts have met the study endpoint (8/25, 32%; 1 PR); 5 high EGFR (5/19, 26.3%), 3 low EGFR (3/6, 50%); 1 pt remained on study drug for 16 months. Toxicity: Grade (Gr)1–2: 23 pts; Gr 3: 7 pts. (abdominal pain, anemia, increased bilirubin and AST, skin infection, vomiting, diarrhea). No pts required dose reduction or removal from study for drug-related toxicity. 21 pts had Gr 1–2 skin rash. All responding pts developed Gr 1(5 pts, 62.5%) or Gr 2 (3 pts, 37.5%) skin rash. Median time to progression (TTP) for all pts: 9.1 wks; median TTP for responding pts: 26.3 wks. Median survival (MS) all pts: 25 wks; MS for responding pts: 44 wks. fCT analysis appears to indicate mixed response of tumor blood flow to OSI-774. Conclusions: OSI-774 is well tolerated in pts with HCC, and provides prolonged stable disease and apparently has the potential to improve survival. Accrual will continue to 40 pts total in each strata. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech NCI