gebhart/patrepeval huggingface dataset:
Expression of recombinant platelet-derived growth factor A- and B-chain homodimers in rat-1 cells and human fibroblasts reveals differences in protein processing and autocrine effects. (1988)

The autocrine effects of platelet-derived growth factor (PDGF) A- and B-chain homodimers (PDGF-AA and PDGF-BB) on rat-1 cells and human fibroblasts have been investigated by using human PDGF A- and B-chain cDNA clones expressed in a retroviral vector. Infection with replication-defective virus carrying the B-chain cDNA resulted in a phenotypical transformation resembling that induced by simian sarcoma virus. The resulting cells were focus forming in monolayer cultures, grew to high saturation densities, and formed large colonies in soft agar. The PDGF A-chain transfectants showed no transformed morphology and lacked focus-forming activity but grew to high saturation density in monolayer culture and formed small colonies in soft agar. A similar but weaker effect was obtained with an A-chain cDNA variant containing a 69-base-pair insertion in the 3' end of the protein-coding domain. A- and B-chain transfectants released PDGF receptor-competing activity into the medium, but only the medium conditioned by the B-chain transfectants possessed potent mitogenic activity on human fibroblasts. Both types of transfectants had downregulated levels of PDGF receptors; however, the B-chain transfectants were downregulated to significantly lower levels. Metabolic labeling and immunoprecipitations with PDGF antiserum showed that the PDGF B-chain protein was processed to a 24-kilodalton cell-associated and a 30-kilodalton secreted dimeric protein. The A-chain protein was rapidly secreted as a 31-kilodalton dimeric protein. The present study shows a marked difference in the autocrine effects of PDGF-AA and -BB expressed under the control of a retroviral promoter and suggests that different biological properties may be assigned to these two PDGF isoforms.
A Fresh Look at Iontophoresis (1984)

The rate of penetration of fluorescein and gentamicin ions into the anterior chamber of the rabbit was increased more than 100-fold by the passage of 1 mamp; the amount of drug that penetrates is better controlled by iontophoresis than by instillation. The potential value, the safety and the limitations of this procedure are discussed, and a theoretical basis for the increase is provided. Practical methods of using iontophoresis in the clinic are described. A 30-s application should result in a therapeutic level of the antibiotic in the anterior segment over a 12-hour period in eyes with an intact epithelium.
Missense Mutations of MADH4 (2004)

These findings have important implications for in vitro functional studies, suggesting that the majority of missense mutations inactivate Madh4 by protein degradation in contrast to those that occur within the MCR.
A general protocol for evaluating the specific effects of DNA replication inhibitors (1993)

Inhibitors of DNA replication in mammalian cells are of great interest because of their potential use in chemotherapy and in cell synchronizing protocols in the laboratory. We have used a combination of isotopic labelling protocols and a two-dimensional gel replicon mapping procedure to determine the specific effects of five different replication inhibitors in cultured cells. Utilizing this protocol, we show that hydroxyurea, aphidicolin, and cytosine arabinoside, three known chain elongation inhibitors, are rather ineffective at preventing fork progression even at relatively high concentrations. In contrast, two related compounds that have been suggested to be G1/S inhibitors (mimosine and ciclopyrox olamine [CPX]) actually appear to inhibit initiation at origins. One of these agents (CPX) appears also to inhibit replication in yeast, opening the possibility that the gene encoding the target (initiator?) protein can first be identified in yeast by genetic approaches and can then be used to isolate the mammalian homologue.
Expression of multidrug resistance protein-3 (multispecific organic anion transporter-D) in human embryonic kidney 293 cells confers resistance to anticancer agents. (1999)

Multidrug resistance-associated protein (MRP)1 and canalicular multispecific organic anion transporter (cMOAT)/MRP2 are ATP-binding cassette (ABC) transporters that confer resistance to natural product cytotoxic drugs. We recently described the complete coding sequences of four human MRP/cMOAT subfamily members and found that, among these proteins, MRP3/MOAT-D is most closely related to MRP1 (58% identity; M. G. Belinsky and G. D. Kruh, Br. J. Cancer, 80: 1342-1349, 1999). In the present study, we sought to determine whether MRP3 is capable of conferring resistance to cytotoxic drugs. To address this question, human embryonic kidney 293 cells were transfected with an MRP3 expression vector, and the drug resistance phenotype of the transfected cells was analyzed. The MRP3-transfected cells displayed approximately 4-fold resistance to etoposide and approximately 2-fold resistance to vincristine, compared with control transfected cells. In addition, approximately 1.7-fold resistance was observed for the antimetabolite methotrexate. Increased resistance was not observed for several other natural product agents, including anthracyclines and Taxol. The MRP-transfected cells exhibited reduced accumulation of radiolabeled etoposide, consistent with the operation of a plasma membrane efflux pump. These results indicate that MRP3 confers resistance to some anticancer agents but that its resistance pattern is distinct from the resistance patterns of other ABC transporters involved in resistance to natural product chemotherapeutic agents.
Analysis of antigenic variation in equine 2 influenza A viruses. (1983)

Influenza outbreaks involving viruses of the H3N8 subtype (equine 2) often occur in vaccinated horses. For this reason, a series of influenza viruses of the H3N8 subtype were examined to determine if antigenic variation could be detected in isolates during the period 1963-81. Antigenic analyses with post-infection ferret sera and monoclonal antibodies showed that the haemagglutinins of recent isolates were antigenically distinguishable from the prototype A/eq/Miami/1/63 and that antigenically distinguishable groups of equine 2 viruses co-circulate in the horse population. Based on these studies, it is recommended that a recent equine strain, A/equine/Fontainebleu/1/79 or A/equine/Kentucky/1/81, serve as an additional prototype strain for this subtype.Antigenic variation in equine 2 viruses may be of epidemiological significance, yet the overall conservation of these strains makes it unlikely that vaccine failures can be attributed solely to antigenic changes in these viruses. A sufficiently potent vaccine, containing a current representative of the most prevalent equine 2 strain, may improve the protection afforded by equine vaccines.
MIF-like activity of natural and recombinant human interferon-gamma and their neutralization by monoclonal antibody. (1985)

By utilizing elutriation-purified human monocytes, we found that human interferon (IFN) inhibits monocyte migration in a manner similar to migration inhibitory factor (MIF) and does it without demonstrable cytotoxicity. We observed that human IFN-gamma is 10 to 300 times more potent in its MIF activity than is IFN-alpha and that monoclonal antibodies (MoAb) can be used to distinguish between them. Studies with recombinant IFN-gamma indicate that the migration inhibition seen with natural IFN-gamma is due to IFN-gamma itself and is not due to co-purification of another lymphokine with the natural IFN-gamma. Although interferons exhibit MIF activities, there are apparently other cytokines, without antiviral activity, that also have MIF activities. MIF from the lymphoblastoid cell line RPMI 1788 was not neutralized by MoAb to IFN. However, MIF activity in supernatant fluid from human peripheral blood lymphocyte cultures stimulated with Con A-Sepharose was completely neutralized with MoAb anti-IFN-gamma. These data indicate that MIF is really a family of cytokines that inhibit macrophage/monocyte migration and that the major portion of MIF activity associated with crude supernatant of mitogen-stimulated lymphocytes is due to IFN-gamma.
Cloning genes for proline biosynthesis from Neisseria gonorrhoeae: identification by interspecific complementation of Escherichia coli mutants (1984)

DNA from Neisseria gonorrhoeae KH45 was partially digested with Sau3A and inserted into the BamHI site of the cloning vector pLES2 . After introduction into Escherichia coli JM83 by transformation, two different size classes of plasmids were isolated that could complement the proAB deletion of JM83 . These plasmids ( pLES4 and pLES7 ) were characterized by restriction endonuclease digestion. Southern hybridization demonstrated that the inserts had sequence homology. Various deletions of these plasmids were constructed that had lost the ability to complement the proA lesion of chi 463, the proB lesion of chi 340, or both (plasmids pLES9 , pLES8 , and pLES10 , respectively). These deleted plasmids were introduced into a proline-requiring strain of N. gonorrhoeae, F62, with plasmids pLES4 , pLES7 , and pLES8 possessing the ability to correct the proline requirement of F62. Further analysis indicated that the hybrid plasmids were stably maintained as plasmids in N. gonorrhoeae.
Effects of cholestyramine on hepatic cholesterol 7α‐hydroxylase and serum 7α‐hydroxycholesterol in the hamster (1999)

Cholestyramine increases activities of hepatic cholesterol 7alpha-hydroxylase and serum levels of 7alpha-hydroxycholesterol. To examine if serum 7alpha-hydroxycholesterol levels parallel with enzyme activity, 0, 0.5, 1, 2, 4, and 10% of cholestyramine was administered to female golden Syrian hamsters for 28 d in the dose-dependent study, and 2% cholestyramine for 0, 1, 3, 7, 14, 21, and 28 d in the time-dependent study. In the dose-dependent study, hepatic and serum cholesterol levels were significantly decreased dose-dependently when more than 0.5% of cholestyramine was fed for 28 d. Cholestyramine increased the cholesterol 7alpha-hydroxylase activity in a dose-dependent manner, while the serum 7alpha-hydroxycholesterol level was essentially unchanged. No correlation was found between the serum level and the hepatic enzyme activity. In the time-dependent study, hepatic and serum cholesterol levels markedly decreased when 2% cholestyramine was fed for longer than 3 d. The serum triglyceride level increased significantly for the first 7 d and then decreased. Cholesterol 7alpha-hydroxylase activity increased significantly as early as day 1, reached maximum activity level on day 7, and then kept the significantly high values until day 28. The serum 7alpha-hydroxycholesterol level significantly increased for the first 7 d and decreased to the pretreatment level thereafter. 7Alpha-hydroxycholesterol levels significantly correlated with serum cholesterol and triglyceride levels. We conclude that the serum 7alpha-hydroxycholesterol level does not always reflect the activity of hepatic cholesterol 7alpha-hydroxylase, when cholesterol metabolism is severely disturbed by cholestyramine.
An Essential Role for Interleukin 10 in the Function of Regulatory T Cells That Inhibit Intestinal Inflammation (1999)

A T helper cell type 1-mediated colitis develops in severe combined immunodeficient mice after transfer of CD45RB(high) CD4(+) T cells and can be prevented by cotransfer of the CD45RB(low) subset. The immune-suppressive activities of the CD45RB(low) T cell population can be reversed in vivo by administration of an anti-transforming growth factor beta antibody. Here we show that interleukin (IL)-10 is an essential mediator of the regulatory functions of the CD45RB(low) population. This population isolated from IL-10-deficient (IL-10(-/-)) mice was unable to protect from colitis and when transferred alone to immune-deficient recipients induced colitis. Treatment with an anti-murine IL-10 receptor monoclonal antibody abrogated inhibition of colitis mediated by wild-type (WT) CD45RB(low) CD4(+) cells, suggesting that IL-10 was necessary for the effector function of the regulatory T cell population. Inhibition of colitis by WT regulatory T cells was not dependent on IL-10 production by progeny of the CD45RB(high) CD4(+) cells, as CD45RB(low) CD4(+) cells from WT mice were able to inhibit colitis induced by IL-10(-/-) CD45RB(high) CD4(+) cells. These findings provide the first clear evidence that IL-10 plays a nonredundant role in the functioning of regulatory T cells that control inflammatory responses towards intestinal antigens.
A new waveguide switch/modulator for integrated optics (1975)

A waveguide optical switch and/or modulator device is described that uses a single-mode waveguide version of the Mach-Zehnder interferometer. A mode selective branching waveguide is used for switching, and modulation can be accomplished without external polarizers in single-mode waveguides. The operation of a 1×2 switch fabricated by diffusion techniques in ZnSe is described.
In Vivo Targeting of Underglycosylated MUC-1 Tumor Antigen Using a Multimodal Imaging Probe (2004)

One of the most difficult challenges of oncology is to improve methods for early tumor detection, which is crucial for the success of cancer therapy and greatly improves the survival rate. Underglycosylated mucin-1 antigen (uMUC-1) is one of the early hallmarks of tumorigenesis and is overexpressed and underglycosylated on almost all human epithelial cell adenocarcinomas as well as in nonepithelial cancer cell lines, as well as in hematological malignancies such as multiple myeloma, and some B-cell non-Hodgkin lymphomas. In this study, we designed, synthesized, and tested a novel multimodal imaging probe specifically recognizing in vivo uMUC-1 antigen in an animal model of human cancer. Furthermore, in vivo magnetic resonance- and near-infrared-imaging experiments on tumor-bearing animals showed specific accumulation of the probe in uMUC-1-positive tumors and virtually no signal in control tumors. We expect that this probe has a potential to greatly aid in screening prospective patients for early cancer detection and in monitoring the efficacy of drug therapy.
Prediction of Individual Brain Maturity Using fMRI (2010)

Group functional connectivity magnetic resonance imaging (fcMRI) studies have documented reliable changes in human functional brain maturity over development. Here we show that support vector machine-based multivariate pattern analysis extracts sufficient information from fcMRI data to make accurate predictions about individuals' brain maturity across development. The use of only 5 minutes of resting-state fcMRI data from 238 scans of typically developing volunteers (ages 7 to 30 years) allowed prediction of individual brain maturity as a functional connectivity maturation index. The resultant functional maturation curve accounted for 55% of the sample variance and followed a nonlinear asymptotic growth curve shape. The greatest relative contribution to predicting individual brain maturity was made by the weakening of short-range functional connections between the adult brain's major functional networks.
Targeting CD20 in Melanoma Patients at High Risk of Disease Recurrence (2012)

Melanomas contain distinct cell subpopulations. Several of these subpopulations, including one expressing CD20, may harbor stem cell-like or tumor-initiating characteristics. We hypothesized that patients at high risk of disease recurrence could benefit from an adjuvant anti-CD20 therapy. Therefore, we initiated a small pilot trial to study the effect of the anti-CD20 antibody rituximab in a group of melanoma patients with stage IV metastatic disease who had been rendered without evident disease by way of surgery, chemotherapy and/or radiation therapy. The major objective was safety, while secondary objectives were description of recurrence-free intervals (RFI) and overall survival (OS). Nine patients received rituximab at 375 mg/m(2) qw for 4 weeks followed by a maintenance therapy every 8 weeks. Treatment was discontinued after 2 years or with disease recurrence. Treatment was well tolerated. After a median observation of 42 months, the median neither of RFI nor of OS has been reached. Despite therapy that ended after 2 years, six out of nine patients are still alive and five of them are recurrence-free. Though the patient number is too small for definitive conclusions, our data may represent a first example of the potential therapeutic value of targeting CD20(+) cell populations-at least for a subset of patients.
A novel dye exclusion method for testing in vitro chemosensitivity of human tumors. (1983)

Dissociated cancer cells are exposed to antineoplastic drugs (5 X 10(4) viable cells/drug for 1 hr or continuously) and cultured for 4 to 6 days in liquid medium. Cells are then stained with Fast green dye, sedimented onto slides with a Cytospin centrifuge, and counterstained with a modified hematoxylin and eosin technique. Dead cells stain with Fast green, and living cells stain with hematoxylin and eosin. Cell kill is calculated as percentage of control based on the relative numbers of living tumor cells, living non-tumor cells, and dead cells. Drug sensitivity could be assayed in 125 of 162 specimens of human neoplasms obtained from malignant effusions (16 of 18), excisional biopsies (31 of 44), needle biopsies (34 of 47), endoscopic biopsies (18 of 23), peripheral blood samples (19 of 20), and bone marrow aspirates (five of seven). The assays were successful (median of ten drugs tested) in: 46 of 64 adenocarcinomas; four of 11 squamous cell carcinomas; five of seven lymphomas; six of seven melanomas; two of four sarcomas; 18 of 20 transitional-cell carcinomas; 14 of 15 small-cell carcinomas; seven of eight myelomas; 12 of 12 chronic lymphocytic leukemias; seven of nine acute leukemias, and four of five "undifferentiated" carcinomas. The assay results demonstrated a strong correlation between the in vitro chemosensitivity of different types of tumors and the known clinical response patterns of these tumors. This assay can be used to determine which specific cells are killed in a heterogeneous cell population. Further work is needed to determine if this assay may be useful in blind screening trials for antineoplastic agents or if it may be of clinical use in predicting response to agents which are not cycle specific.
Pathogenesis and Treatment of Acute Hematogenous Osteomyelitis: Evaluation of Current Views with Reference to an Animal Model (1986)

Antibiotic therapy and surgical drainage of the bone are the most commonly accepted forms of therapy for acute hematogenous osteomyelitis; the efficacy of these two treatment modalities, however, has not been fully established. Treatment regimens remain empiric and open to much controversy. Many contentious issues concerning the management of this disease have arisen because the natural history of the untreated condition has not been properly understood, because therapeutic regimens alternative to those empirically initiated and perpetuated have not been adequately tested, and because most follow-up studies have dealt with small numbers of patients over relatively short periods. A highly reproducible animal model of acute hematogenous osteomyelitis was developed and utilized in a reexamination of issues regarding the natural history and pathology of the disease and the influence of appropriate treatment.
Hydraulic Fracturing To Improve Production (2010)

Tech 101 - Consultant Ali Daneshy presents an overview of hydraulic fracturing. Reasons for Hydraulic Fracturing In their natural state, most oil and gas wells do not produce at their optimum level, but hydraulic fracturing can address multiple challenges to efficient production. Radial flow from the reservoir into the wellbore is not an efficient flow regime. As the fluid approaches the wellbore, it has to pass through successively smaller and smaller areas. This causes “jamming” of the fluid and reduction in flow. If one were to complete the well such that the radial flow changes to nearly linear, then the change in flow pattern will increase well productivity. A properly designed and executed hydraulic fracture can change flow from radial to nearly linear (Fig. 1). Nearwellbore permeability in most formations is reduced by drilling, cementing, and completion operations. Theoretically, one can show that this permeability reduction causes substantial reductions in production rates (Fig. 2). Hydraulic fracturing can extend the reach of the wellbore beyond the damaged area and abate its negative effect on production. Hydraulic fracturing extends the reach of the wellbore far into the formation. Production is therefore controlled by the properties of the average reservoir reached by the fracture, instead of the much smaller near-wellbore region. The net effect is a reduction in the risk of drilling into less- or nonproductive zones.
Functional Foods (2000)

Part 1 General issues: Defining functional foods EU legislation and functional foods: a case study US legislation and functional health claims. Part 2 Functional foods and health: Colonic functional foods Coronary heart disease Antitumour properties Functional foods and acute infections. Part 3 Developing functional food products: Maximising the functional benefits of plant foods Developing functional ingredients: a case study Functional fats and spreads Functional confectionery Probiotic functional foods Dietary fibre functional products.
Vaccines : new generation immunological adjuvants (1995)

During the last decade or so vaccine development has been facilitated by rapid advances in molecular and cell biology. These have laid the foundations of a new generation of vaccines exemplified by subunit vaccines produced through gene cloning and by synthetic peptides mimicking small regions of proteins on the outer coat of viruses. Such peptide are capable of eliciting virus-neutralizing antibodies. Unfortunately, subunit and peptide vaccines are only weakly or non immunogenic in the absence of immunological adjuvants that are known to augment specific cell-mediated immune responses to the antigens and to promote the formation of protective antibodies. This book contains the proceedings of the 4th NATO Advanced Studies Institute (ASI) Vaccines: New Generation Immunological Adjuvants held at Cape Sounion Beach, Greece, during 24 June -5 . July 1994 and deals in depth with both theoretical and practical aspects of vaccinology. These include the role of antigen presenting cells in the induction of immune responses. immunopotentiation by a variety of new generation immunological adjuvants and vaccine carriers. and recent advances and perspectives in experimental vaccines as well as vaccinatioll with nucleic acids. We express our appreciation to Dr. K. Dalsgaard and Dr. J. L. Virelizier for their cooperatioll in planning the ASI and to Mrs. Concha Pening for her excellent production of the manuscripts. The ASI was held under the sponsorship of NATO Scientific Affairs Division and generously co-sponsored by SmithKline Beecham Pharmaceuticals (Philadelphia).
Induction of ICAM 1 expression on bladder tumours by BCG immunotherapy. (1994)

Untreated superficial bladder carcinoma cells do not express ICAM 1 or 2, but these important immunological molecules were expressed in the stromal areas of tissue. Importantly, neoplastic cells in the urine expressed ICAM 1 after immunotherapy. This molecule can render bladder tumour cells vulnerable to non-antigen specific cytotoxicity mediated by activated lymphocytes.