gebhart/patrepeval huggingface dataset:
Liposomes for tumor-targeted therapy. (2002)

Liposomes are the models of membranes. Liposomalization of various drugs has revealed the enhancement of their efficacy : Since liposomes can reduce the side effect of the drugs by the site-specific delivery, intracellular targeting, and controlled release of drugs, many functional liposomes have been developed including cationic liposomes and antibody-conjugating immunoliposomes. In this article, the preparation and characterization of functional liposomes are discussed. We have developed intracellular hyperthermia using magnetic nanoparticles (magnetites) by the feature that magnetites can generate heat under high frequency alternative magnetic field. In addition, magnetites affect the magnetic gradient in a magnetic field and those can be used as a contrast enhancement reagent for MRI. Therefore, if magnetite can be accumulated only in tumor tissue, they can afford cancer diagnosis and tumor-specific hyperthermia. To deliver the magnetites toward tumors, two kinds of functional liposomes have been developed, which were “magnetite cationic liposomes(IVICLs)” and “Fab'-conjugating magnetoliposomes (FMLs)”. MCLs were designed for the intratumor injection and showed the high affinity to the tumor cells. On the other hands, FMLs were designed for “missile liposomes” which can accumulate in the tumor by antigens-antibody reaction even in the case of intravascular injection. Here, we review these functional liposomes and discussed how to achieve the ultimate goal for tumor targeting.
Blood-on-a-Chip (2005)

Accurate, fast, and affordable analysis of the cellular component of blood is of prime interest for medicine and research. Yet, most often sample preparation procedures for blood analysis involve handling steps prone to introducing artifacts, whereas analysis methods commonly require skilled technicians and well-equipped, expensive laboratories. Developing more gentle protocols and affordable instruments for specific blood analysis tasks is becoming possible through the recent progress in the area of microfluidics and lab-on-a-chip-type devices. Precise control over the cell microenvironment during separation procedures and the ability to scale down the analysis to very small volumes of blood are among the most attractive capabilities of the new approaches. Here we review some of the emerging principles for manipulating blood cells at microscale and promising high-throughput approaches to blood cell separation using microdevices. Examples of specific single-purpose devices are described together with integration strategies for blood cell separation and analysis modules.
Expression of skin-derived antileukoproteinase (SKALP) in reconstructed human epidermis and its value as a marker for skin irritation (1998)

For the investigation of the skin irritancy potential of chemicals in an in vitro model, it is necessary to have sensitive end-points that predict the effects on native human skin. Our aim was to investigate whether the induction of the proteinase inhibitor SKALP in reconstructed epidermis can be used as a marker. The influence of culture conditions and the effect of topical application of sodium lauryl sulfate and oleic acid on SKALP expression were evaluated using immunohistochemistry and Northern blotting. SKALP expression was induced by serum, epidermal growth factor and fibroblasts. In the presence of retinoic acid and 1,25-dihydroxyvitamin D3 SKALP expression was inhibited, whereas supplementation with ascorbic acid and a-tocopherol had no effect. Tape-stripping of excised skin and topical treatment with sodium lauryl sulfate induced SKALP protein expression. Application of sodium lauryl sulfate and oleic acid on reconstructed epidermis also induced SKALP at the protein level but no significant effects could be demonstrated at mRNA levels. In conclusion, SKALP expression, which was increased upon application of sodium lauryl sulfate and oleic acid, can be used as an in vitro end-point for skin irritancy, irrespective of the modifying effects of culture conditions.
An imprinted locus associated with transient neonatal diabetes mellitus (2000)

Recently, we reported the localization of a gene for transient neonatal diabetes mellitus (TNDM), a rare form of childhood diabetes, to an approximately 5.4 Mb region of chromosome 6q24. We have also shown that TNDM is associated with both paternal uniparental disomy (UPD) of chromosome 6 and paternal duplications of the critical region. The sequencing of P1-derived artificial chromosome clones from within the region of interest has allowed us to further localize the gene and to investigate the methylation status of the region. The gene is now known to reside in a 300-400 kb region of 6q24 which contains several CpG islands. At one island we have demonstrated differential DNA methylation between patients with paternal UPD of chromosome 6 and normal controls. In addition, two patients with TNDM, in whom neither paternal UPD of chromosome 6 nor duplication of 6q24 have been found, show a DNA methylation pattern identical to that of patients with paternal UPD of chromosome 6. Control individuals show a hemizygous methylation pattern. These results show that TNDM can be associated with a methylation change and identify a novel methylation imprint on chromosome 6 associated with TNDM.
Molecular Cloning of the Feline Telomerase Reverse Transcriptase (TERT) Gene and Its Expression in Cell Lines and Normal Tissues (2003)

Telomerase is a kind of reverse transcriptase which synthesizes and elongates telomeres. Telomerase activity is detected in many naturally occurring tumors and its expression appears to play an important role in the immortalization of tumor cells. In this study, cDNA encoding the feline telomerase reverse transcriptase (TERT) gene was cloned partially from a feline lymphoma cell line. The clone obtained in this study was 237 bp long including a reverse transcriptase motif 2, and was shown to have amino acid sequence similarity of 81.0% and 58.2% with human and mouse TERT cDNAs, respectively. TERT mRNA expression was detected in telomerase-positive cells (FL74, FT-1, 3201, FKNp, FONp, and FYMp), and was not detected in telomerase-negative cells (normal fibroblasts and CRFK). TERT mRNA was detected in various normal tissues including the spleen, pancreas, stomach, cerebrum, testis, bone marrow, lymph node and thymus, and relatively high-level expression was observed in the small bowel and large bowel. No expression of TERT mRNA was detected in the liver, adrenal gland, urinary bladder and lung. The TERT cDNA clone and the results obtained in this study will be useful for further investigation of feline tumors.
Pharmacotherapy of gastrointestinal stromal tumours (2003)

AbstractGastrointestinal stromal tumours (GIST) are a relatively rare, but well characterised clinical entity. This tumour is defined by a predominantly spindle-cell morphology and its pathobiology by the presence of Kit (receptor tyrosine kinase). The majority of GIST have a gain of function mutation in an exon hot spot that leads to constitutive activation of Kit, promoting proliferation and anti-apoptotic signalling. Imatinib mesylate (Gleevec™, Glivec®, Novartis) is a specific inhibitor of Kit kinase activation and in Phase II clinical trials, it has proven to be remarkably effective in heavily pre-treated patients with advanced GIST. Molecular determinants of response and resistance are the subject of ongoing investigations. Additionally, clinical trials are underway to explore the use of imatinib mesylate in the adjuvant setting. These initial evaluations with imatinib mesylate provide proof of concept for hypothesis driven, rational drug design of selective signal transduction inhibitors in the management of solid tumour malignancies.Keywordsgastrointestinal stromal tumourimatinib mesylatetyrosine kinase inhibitor
The bovine papillomavirus E2 protein modulates the assembly of but is not stably maintained in a replication-competent multimeric E1-replication origin complex. (1994)

Initiation of bovine papillomavirus (BPV) DNA synthesis in vivo and in vitro depends on the interaction of the viral initiator protein E1 with the replication origin (ori+ DNA). The viral E2 protein assists this interaction, resulting in a cooperative assembly of both proteins on the replication origin. Using gel mobility-shift experiments, we demonstrate that in the presence of both E1 and E2 proteins two classes of ori+ DNA complexes were formed: complex 1 (c1) and complex 2 (c2). Formation of c1 depended on both the E1 and E2 proteins and both proteins were contained within c1. The generation of c2 was dependent on the E1 protein and could be enhanced by E2, but the E2 protein was not detected within c2. At high E2/E1 ratios, c1 was the dominant complex formed. Under these conditions, E1-dependent BPV DNA synthesis in vitro was inhibited. At low E2/E1 ratios, the stimulation of c2 was correlated with the stimulation of BPV DNA replication by E2 in vitro. These data suggest that E2 assists E1 in the formation of an intermediate c1 complex, which is replication inactive. The c1 complex is converted in turn to the replication-active c2 complex, which contains E1 but lacks E2. We propose that the ratios of c1 and c2 formed in response to the levels of E1 and E2 protein determine the potential for BPV DNA synthesis in vitro and in vivo and may contribute to copy number regulation of BPV plasmids within the cell.
Mannose‐binding lectin: targeting the microbial world for complement attack and opsonophagocytosis (2001)

Mannose-binding lectin (MBL) is an important constituent of the innate immune system. This protein binds through multiple lectin domains to the repeating sugar arrays that decorate many microbial surfaces, and is then able to activate the complement system through a specific protease called MBL-associated protease-2. We have used flow cytometry to study both the binding of MBL to microorganisms and the subsequent activation of complement. For selected Gram-negative organisms, such as Salmonella and Neisseria, we have examined the relative roles of lipopolysaccharide (LPS) structure and capsule in determining binding and conclude that the LPS is of major importance. Our results from studies with several clinically relevant organisms also show that MBL binding detected by flow cytometry leads to measurable activation of purified C4, suggesting that the bound lectin is capable of initiating opsonophagocytosis and/or bacterial lysis. There is an increasing literature suggesting that MBL deficiency, which mainly results from three relatively common single point mutations in exon 1 of the gene, predisposes both to infection by extracellular pathogens and to autoimmune disease. In addition, the protein also modulates disease severity, at least in part through a complex, dose-dependent influence on cytokine production. The mechanisms and signalling pathways involved in such processes remain to be elucidated.
Retention of antibacterial activity and bacterial colonization of antiseptic-bonded central venous catheters (1996)

We determined how long antiseptic impregnation with silver sulphadiazine and chlorhexidine (SCC) on polyurethane central venous double- or triple-lumen catheters is retained in vivo. A total of 116 antiseptic catheters were tested for antibacterial activity in an in-vitro bioassay after various periods of iv catheterization. Segments from the subcutaneous (sc) and intravenous (iv) portions of the catheters were cultured. The results of test antiseptic catheters were compared with those from 117 noncoated control (c) catheters. Retention of antibacterial activity followed an exponential curve and lasted for up to 520 h after catheter insertion. Significant differences (P = 0.0001) between SSC and C catheters were noticed with regard to the quantitative level of bacterial colonization (SSC-sc 87 +/- 34 vs C-sc 584 +/- 122; SSC-iv 52 +/- 17 vs C-iv 286 +/- 57; all values are given as mean cfu +/- S.E.M.), and the frequency of bacterial colonization (SSC-sc 20.7% vs C-sc 38.5%, P = 0.0047; SSC-iv 18.1% vs C-iv 30.8%, P = 0.0361). There was no significant difference between the incidence of catheter-related bacteraemia in the test (n = 0) and control groups (n = 3) (P = 0.2573). Further prospective studies are required to delineate the role of antiseptic catheters in preventing catheter-related infections.
A Perfluoroaryl-Cysteine S N Ar Chemistry Approach to Unprotected Peptide Stapling (2013)

We report the discovery of a facile transformation between perfluoroaromatic molecules and a cysteine thiolate, which is arylated at room temperature. This new approach enabled us to selectively modify cysteine residues in unprotected peptides, providing access to variants containing rigid perfluoroaromatic staples. This stapling modification performed on a peptide sequence designed to bind the C-terminal domain of an HIV-1 capsid assembly polyprotein (C-CA) showed enhancement in binding, cell permeability, and proteolytic stability properties, as compared to the unstapled analog. Importantly, chemical stability of the formed staples allowed us to use this motif in the native chemical ligation-mediated synthesis of a small protein affibody that is capable of binding the human epidermal growth factor 2 receptor.
A Comparison of Four Common Atmospheric Correction Methods (2007)

Four atmospheric correction methods, two relative and two absolute, were compared in this study. Two of the methods (PIF and RCS) were relative approaches; COST is an absolute image-based method and 6S, an absolute modeling method. The methods were applied to the hazy bands 1 through 4 of a Landsat TM scene of the year 1997, which was being used in a change detection project. The effects of corrections were studied in woodland patches. Three criteria, namely (a) image attributes; (b) image classification results, and (c) landscape metrics, were used for comparing the performance of the correction methods. Average pixel values, dynamic range, and coefficient of variation of bands constituted the first criterion, the area of detected vegetation through image classification was the second criterion, and patch and landscape measures of vegetation the third criterion. Overall, the COST, RCS, and 6S methods performed better than PIF and showed more stable results. The 6S method produced some negative values in bands 2 through 4 due to the unavailability of some data needed in the model. Having to use only a single set of image pixels for normalization in the PIF method and the difficulty of selecting such samples in the study area may be the reasons for its poor performance.
Antineoplastic activity of two taxol derivatives on an ovarian tumor xenografted into nude mice. (1988)

In order to compare the antineoplastic activities of taxol A, taxol B, a mixture of the two (taxol A 72%) and vinblastine, a human ovarian tumor serially transplanted into 104 female athymic mice was used. In the first experiment (11th passage), the antineoplastic activities of taxol A, taxol B and the mixture taxol AB were tested. The same dose was used in each case (12.5 mg/kg i.e. 1/20 of the evaluated LD50 value). It was administered subcutaneously for 5 consecutive days. Three courses of treatment were performed, with 2 rest periods of 1 week in between. All the taxol derivatives produced a statistically significant delay in the tumor growth. However, taxol B had the lowest chemotherapeutic response. In the second experiment (18th passage), different dose levels were administered (mixture 12.5 mg/kg/day x 4 - taxol A 8.8. mg/kg/day x 4 - taxol B 3.5 mg/kg/day x 4 - vinblastine 0.5 mg/kg/day x 2). For all the taxol derivatives 4 treatment courses with 3 rest periods of 4 days were used, and for vinblastine 4 treatment courses with 3 rest periods of 1 week. At the end of the second experiment, vinblastine, taxol A and a mixture of the two showed similar significant activity, whereas no objective antitumor response was observed following the taxol B treatment at the dose level chosen. The experimental results obtained clearly demonstrate that, in the taxane system, the greatest degree of antineoplastic activity can be attributed to taxol A.
Acute otitis media: making sense of recent guidelines on antimicrobial treatment. (2005)

High-dose amoxicillin (80 to 90 mg/kg/d divided twice daily) remains the drug of choice for treatment of acute otitis media despite increasing antimicrobial resistance. For persistent or recurrent acute otitis media, guidelines recommend high-dose amoxicillin/clavulanate (90/6.4 mg/kg/d), cefdinir, cefprozil, cefpodoxime, cefuroxime, or ceftriaxone. Increasing the dose of amoxicillin does not cover infection with beta-lactamase-producing pathogens; add the beta-lactamase inhibitor clavulanate to amoxicillin, or choose a cephalosporin with good activity against S pneumoniae and good beta-lactamase stability. Key factors for enhancing compliance are taste of suspension, dosing frequency, and duration of therapy.
Why Do We Not All Have Proteinuria? An Update of Our Current Understanding of the Glomerular Barrier (2004)

The key question is not why some patients have proteinuria but rather why not all people have it. In the present review, we will present an update on the glomerular barrier after the recent breakthroughs in podocyte biology. In particular, we will discuss the role of the endothelium, which seems to be a neglected part of the glomerular membrane.
Cloning of human ovarian cancer cells in soft agar from malignant and peritoneal washings. (1980)

Abstract We have used a technique for the direct cloning in soft agar of human ovarian cancer cells (Hamburger et al. , Cancer Res., 38: 3438–3444, 1978) to grow ovarian cancer colonies from 81% of malignant effusions obtained from 27 patients with ovarian cancer as well as from 92% of cytologically malignant peritoneal washings from 13 patients, collected in the absence of ascites. Ovarian cancer colonies were grown from washings obtained at peritoneoscopy or via an indwelling Tenckhoff dialysis catheter. No ovarian cancer colony growth was observed in cytologically negative peritoneal washings from 13 patients with ovarian cancer. Sufficient clonogenic malignant cells were collected by copious peritoneal lavage to allow for in vitro chemotherapy sensitivity testing using this same assay in three of six patients. These results indicate that the sensitivity of human ovarian cancer cells to antitumor agents can be determined even in patients without malignant effusion or readily biopsiable tumors if they have malignant peritoneal washings. Thirty separate in vitro chemotherapy sensitivity assays were performed using Adriamycin, cis -platinum, melphalan, and 5-fluorouracil. In previously treated patients, there were no instances of in vitro sensitivity using these agents at doses approximating clinically achievable plasma levels. However, in untreated patients, in vitro sensitivity to melphalan and Adriamycin was observed. These in vitro results correspond to clinically observed patterns of chemotherapy sensitivity in patients with ovarian cancer and provide indirect evidence that the stem cell assay is predictive for in vitro sensitivity to antitumor agents.
Effect of Mupirocin Treatment on Nasal, Pharyngeal, and Perineal Carriage of Staphylococcus aureus in Healthy Adults (2005)

Nasal carriage of Staphylococcus aureus is an important risk factor for S. aureus infections. Mupirocin nasal ointment is presently the treatment of choice for decolonizing the anterior nares. However, recent clinical trials show limited benefit from mupirocin prophylaxis in preventing nosocomial S. aureus infections, probably due to (re)colonization from extranasal carriage sites. Therefore, we studied the effectiveness of mupirocin nasal ointment treatment on the dynamics of S. aureus nasal and extranasal carriage. Twenty noncarriers, 26 intermittent carriers, and 16 persistent carriers had nasal, throat, and perineum samples taken 1 day before and 5 weeks after mupirocin treatment (twice daily for 5 days) and assessed for growth of S. aureus. The identities of cultured strains were assessed by restriction fragment length polymorphisms of the coagulase and protein A genes. The overall carriage rate (either nasal, pharyngeal, or perineal carrier or a combination) was significantly reduced after mupirocin treatment from 30 to 17 carriers (P = 0.003). Of the 17 carriers, 10 (60%) were still colonized with their old strain, 6 (35%) were colonized with an exogenous strain, and 1 (5%) was colonized with both. Two noncarriers became carriers after treatment. The acquisition of exogenous strains after mupirocin treatment is a common phenomenon. The finding warrants the use of mupirocin only in proven carriers for decolonization purposes. Mupirocin is effective overall in decolonizing nasal carriers but less effective in decolonizing extranasal sites.
Feline Immunodeficiency Virus Lacks Sensitivity to the Antiviral Activity of Feline IFN- γ (2001)

The antiviral activity of recombinant feline interferon-gamma (rFeIFN-gamma) against feline immunodeficiency virus (FIV) was investigated. A persistently FIV(Bang)-infected feline T cell line (FeT-J/Bang) was treated with either rFeIFN-omega, rFeIFN-gamma, or recombinant human IFN-alpha2 (rHuIFN-alpha2), and the culture fluids were tested for antiviral activity by reverse transcriptase (RT) assay. FeT-J/Bang cell cultures treated with rFeIFN-omega showed dose-dependent inhibition of RT activity. In contrast, rFeIFN-gamma treatment had no antiviral effect on FIV replication but instead caused a statistically significant enhancement on day 9 of culture. Antiviral activity of rFeIFN-gamma was also tested on feline peripheral blood mononuclear cells (PBMC). PBMC cultures were inoculated with FIV(Bang) and simultaneously treated with either rFeIFN-omega, rFeIFN-gamma, or rHuIFN-alpha2. FeIFN-gamma had no effect on FIV replication, unlike the rFeIFN-omega and rHuIFN-alpha2, which had strong anti-FIV effects. In another study, rFeIFN-gamma treatment was initiated 3 days before FIV(Bang) infection, the day of FIV(Bang) infection, or 3 days post-FIV(Bang) infection and then tested for antiviral activity. The time of initiating rFeIFN-gamma treatment had no effect on the antiviral activity. Hence, these results suggest that unlike rHuIFN-alpha2 and rFeIFN-omega, rFeIFN-gamma has no inhibitory effect on FIV replication in PBMC but causes a slight enhancement in a feline T cell line.
Large Store-operated Calcium Selective Currents Due to Co-expression of Orai1 or Orai2 with the Intracellular Calcium Sensor, Stim1 (2006)

The molecular nature of store-operated Ca(2+)-selective channels has remained an enigma, due largely to the continued inability to convincingly demonstrate Ca(2+)-selective store-operated currents resulting from exogenous expression of known genes. Recent findings have implicated two proteins, Stim1 and Orai1, as having essential roles in store-operated Ca(2+) entry across the plasma membrane. However, transient overexpression of these proteins on their own results in little or no increase in store-operated entry. Here we demonstrate dramatic synergism between these two mediators; co-transfection of HEK293 cells with Stim1 and Orai1 results in an approximate 20-fold increase in store-operated Ca(2+) entry and Ca(2+)-selective current. This demonstrates that these two proteins are limiting for both the signaling and permeation mechanisms for Ca(2+)-selective store-operated Ca(2+) entry. There are three mammalian homologs of Orai1, and in expression experiments they all produced or augmented store-operated Ca(2+) entry with efficacies in the order Orai1 > Orai2 > Orai3. Stim1 apparently initiates the signaling process by acting as a Ca(2+) sensor in the endoplasmic reticulum. This results in rearrangement of Stim1 within the cell and migration toward the plasma membrane to regulate in some manner Orai1 located in the plasma membrane. However, we demonstrate that Stim1 does not incorporate in the surface membrane, and thus likely regulates or interacts with Orai1 at sites of close apposition between the plasma membrane and an intracellular Stim1-containing organelle.