gebhart/patrepeval huggingface dataset:
Ability of Transplanted Cultured Epithelium to Respond to Dermal Papillae (2001)

Cultured epithelium has been used successfully in the treatment of extensive burns. Regenerated epidermis, however, lacks such as hair follicles and sweat glands that are common in mammalian skin. We attempted to determine whether cultured epithelium could be induced to form hair follicles by dermal papillae, which are most important for the morphogenesis and growth of hair follicles. We cultivated adult rat sole keratinocytes, obtained the cultured epithelium, and prepared recombinants consisting of cultured epithelium and fresh dermal papillae with or without the sole dermis. These recombinants were then transplanted underneath the dermis of the dorsal skin of syngeneic rats or athymic mice. Histologic examination revealed that the transplanted cultured epithelium formed the follicular structures with sebaceous gland-like structure following induction of the dermal papillae, especially when supported by the dermis. We concluded that transplanted cultured epithelium of adult rat sole keratinocytes can respond to growth signals from adult dermal papillae.
Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. (1995)

Obesity is frequently associated with insulin resistance and abnormal glucose homeostasis. Recent studies in animal models have indicated that TNF-alpha plays an important role in mediating the insulin resistance of obesity through its overexpression in fat tissue. However, the mechanisms linking obesity to insulin resistance and diabetes in humans remain largely unknown. In this study we examined the expression pattern of TNF-alpha mRNA in adipose tissues from 18 control and 19 obese premenopausal women by Northern blot analysis. TNF-alpha protein concentrations in plasma and in conditioned medium of explanted adipose tissue were measured by ELISA. Furthermore, the effects of weight reduction by dietary treatment of obesity on the adipose expression of TNF-alpha mRNA were also analyzed in nine premenopausal obese women, before and after a controlled weight-reduction program. These studies demonstrated that obese individuals express 2.5-fold more TNF-alpha mRNA in fat tissue relative to the lean controls (P < 0.001). Similar increases were also observed in adipose production of TNF-alpha protein but circulating TNF-alpha levels were extremely low or undetectable. A strong positive correlation was observed between TNF-alpha mRNA expression levels in fat tissue and the level of hyperinsulinemia (P < 0.001), an indirect measure of insulin resistance. Finally, body weight reduction in obese subjects which resulted in improved insulin sensitivity was also associated with a decrease in TNF-alpha mRNA expression (45%, P < 0.001) in fat tissue. These results suggest a role for the abnormal regulation of this cytokine in the pathogenesis of obesity-related insulin resistance.
An initiator of carcinogenesis selectively and stably inhibits stem cell differentiation: a concept that initiation of carcinogenesis involves multiple phases. (1985)

A concept of carcinogenesis was recently devised in our laboratory that suggests the development of defects in the control of cell differentiation is associated with an early phase of carcinogenesis. To test this proposal directly, the effects of an initiator of carcinogenesis (i.e., UV irradiation) on proadipocyte stem cell differentiation and proliferation was assayed. In this regard, 3T3 T proadipocytes represent a nontransformed mesenchymal stem cell line that possesses the ability to regulate its differentiation at a distinct state in the G1 phase of the cell cycle as well as the ability to regulate its proliferation at two additional G1 states that are induced by culture in growth factor-deficient or nutrient-deficient microenvironments. The results establish that a low dosage of 254 nm UV irradiation selectively and stably inhibits the differentiation of a high percentage of proadipocyte stem cells without significantly altering their ability to regulate cellular proliferation in growth factor-deficient or nutrient-deficient culture conditions. Differentiation-defective proadipocyte stem cells are demonstrated not to be completely transformed but to show an increased spontaneous transformation rate, as evidenced by the formation of type III foci in high density cell cultures. These data support the role of defects in the control of differentiation in the initiation of carcinogenesis. Other data, however, also suggest that additional cellular defects must be expressed for a cell to be completely initiated. These observations support a concept that the initiation of carcinogenesis involves multiple phases.
Interleukin-2 enhancement of cytotoxicity by humanized monoclonal antibody M195 (anti-CD33) in myelogenous leukemia. (1995)

Humanized M195 (HuM195) is a genetically engineered, human IgG1 version of the parent M195, a mouse immunoglobulin G2a, anti-CD33 monoclonal antibody which reacts with early myeloid progenitor cells and myelogenous leukemia cells. In Phase I studies in patients with relapsed and refractory myelogenous leukemia, HuM195 safely targeted to sites of disease and was nonimmunogenic. HuM195 shows only modest capability of antibody-dependent cellular cytotoxicity (ADCC) against target HL60 cells and minimal cytolytic activity mediated by human complement. Therefore, efforts were made to enhance ADCC using cytokines. gamma-Interferon, granulocyte-macrophage colony-stimulating factor, and granulocyte colony-stimulating factor did not promote neutrophil-mediated ADCC with HuM195. However, interleukin-2 (IL-2) showed a range of 2-6-fold increases in ADCC against fresh myelogenous leukemia cells and HL60 cells over that seen with HuM195 or low-dose IL-2 alone. ADCC potency was not improved further by the use of homodimeric HuM195. Flow cytometry and Fc receptor-blocking experiments showed that CD16(+) cells were essential for IL-2-enhanced ADCC. As compared to HL60 cells, a multidrug-resistant line of HL60 cells was at least as susceptible to killing by IL-2 or HuM195 or in combination, suggesting that the mechanism of killing may be active against cells surviving and resistant to chemotherapy. Since these in vitro levels of IL-2 and HuM195 can be safely achieved in patients, the enhancement of HuM195 ADCC with low-dose IL-2 is a possible strategy that may be used in vivo to eliminate minimal disease in future trials of patients with myeloid leukemias.
Dietary Roles of Non-Starch Polysachharides in Human Nutrition: A Review (2012)

Nonstarch polysaccharides (NSPs) occur naturally in many foods. The physiochemical and biological properties of these compounds correspond to dietary fiber. Nonstarch polysaccharides show various physiological effects in the small and large intestine and therefore have important health implications for humans. The remarkable properties of dietary NSPs are water dispersibility, viscosity effect, bulk, and fermentibility into short chain fatty acids (SCFAs). These features may lead to diminished risk of serious diet related diseases which are major problems in Western countries and are emerging in developing countries with greater affluence. These conditions include coronary heart disease, colo-rectal cancer, inflammatory bowel disease, breast cancer, tumor formation, mineral related abnormalities, and disordered laxation. Insoluble NSPs (cellulose and hemicellulose) are effective laxatives whereas soluble NSPs (especially mixed-link β-glucans) lower plasma cholesterol levels and help to normalize blood glucose and insulin levels, making these kinds of polysaccharides a part of dietary plans to treat cardiovascular diseases and Type 2 diabetes. Moreover, a major proportion of dietary NSPs escapes the small intestine nearly intact, and is fermented into SCFAs by commensal microflora present in the colon and cecum and promotes normal laxation. Short chain fatty acids have a number of health promoting effects and are particularly effective in promoting large bowel function. Certain NSPs through their fermented products may promote the growth of specific beneficial colonic bacteria which offer a prebiotic effect. Various modes of action of NSPs as therapeutic agent have been proposed in the present review. In addition, NSPs based films and coatings for packaging and wrapping are of commercial interest because they are compatible with several types of food products. However, much of the physiological and nutritional impact of NSPs and the mechanism involved is not fully understood and even the recommendation on the dose of different dietary NSPs intake among different age groups needs to be studied.
Energy Dysfunction as a Predictor of Outcome after Moderate or Severe Head Injury: Indices of Oxygen, Glucose, and Lactate Metabolism (2003)

During the first 6 days after moderate or severe TBI, CMRO2 and arterial lactate levels are the strongest predictors of neurologic outcome. However, the frequent occurrence of abnormal brain lactate uptake despite only moderate elevations in arterial lactate levels in the favorable outcome patients suggests the brain's ability to use lactate as a fuel may be another key outcome predictor. Future studies are needed to determine to what degree nonglycolytic energy production from alternative fuels such as lactate occurs after TBI and whether alternative fuel administration is a viable therapy for TBI patients.
In vivo two-photon calcium imaging of neuronal networks (2003)

Two-photon calcium imaging is a powerful means for monitoring the activity of distinct neurons in brain tissue in vivo. In the mammalian brain, such imaging studies have been restricted largely to calcium recordings from neurons that were individually dye-loaded through microelectrodes. Previous attempts to use membrane-permeant forms of fluorometric calcium indicators to load populations of neurons have yielded satisfactory results only in cell cultures or in slices of immature brain tissue. Here we introduce a versatile approach for loading membrane-permeant fluorescent indicator dyes in large populations of cells. We established a pressure ejection-based local dye delivery protocol that can be used for a large spectrum of membrane-permeant indicator dyes, including calcium green-1 acetoxymethyl (AM) ester, Fura-2 AM, Fluo-4 AM, and Indo-1 AM. We applied this dye-loading protocol successfully in mouse brain tissue at any developmental stage from newborn to adult in vivo and in vitro. In vivo two-photon Ca2+ recordings, obtained by imaging through the intact skull, indicated that whisker deflection-evoked Ca2+ transients occur in a subset of layer 2/3 neurons of the barrel cortex. Thus, our results demonstrate the suitability of this technique for real-time analyses of intact neuronal circuits with the resolution of individual cells.
Hepatic Stellate Cells: Protean, Multifunctional, and Enigmatic Cells of the Liver (2008)

The hepatic stellate cell has surprised and engaged physiologists, pathologists, and hepatologists for over 130 years, yet clear evidence of its role in hepatic injury and fibrosis only emerged following the refinement of methods for its isolation and characterization. The paradigm in liver injury of activation of quiescent vitamin A-rich stellate cells into proliferative, contractile, and fibrogenic myofibroblasts has launched an era of astonishing progress in understanding the mechanistic basis of hepatic fibrosis progression and regression. But this simple paradigm has now yielded to a remarkably broad appreciation of the cell's functions not only in liver injury, but also in hepatic development, regeneration, xenobiotic responses, intermediary metabolism, and immunoregulation. Among the most exciting prospects is that stellate cells are essential for hepatic progenitor cell amplification and differentiation. Equally intriguing is the remarkable plasticity of stellate cells, not only in their variable intermediate filament phenotype, but also in their functions. Stellate cells can be viewed as the nexus in a complex sinusoidal milieu that requires tightly regulated autocrine and paracrine cross-talk, rapid responses to evolving extracellular matrix content, and exquisite responsiveness to the metabolic needs imposed by liver growth and repair. Moreover, roles vital to systemic homeostasis include their storage and mobilization of retinoids, their emerging capacity for antigen presentation and induction of tolerance, as well as their emerging relationship to bone marrow-derived cells. As interest in this cell type intensifies, more surprises and mysteries are sure to unfold that will ultimately benefit our understanding of liver physiology and the diagnosis and treatment of liver disease.
Mortality and Cardiovascular Disease in Type 1 and Type 2 Diabetes (2017)

In Sweden from 1998 through 2014, mortality and the incidence of cardiovascular outcomes declined substantially among persons with diabetes, although fatal outcomes declined less among those with type 2 diabetes than among controls. (Funded by the Swedish Association of Local Authorities and Regions and others.).
Rolling Loop Scan: An Approach Featuring Ring-Closing Metathesis for Generating Libraries of Peptides with Molecular Shapes Mimicking Bioactive Conformations or Local Folding of Peptides and Proteins (1999)

Libraries of loop-containing peptides (such as the one shown schematically) can be prepared from bis-N-alkylated peptides by ring-closing metathesis. In a general solid-phase procedure the peptides are accessible by site-specific N-alkylation. Since the amino acid side chains are not involved in cyclization, they remain available for interaction with, for example, a receptor.
Differential effect of dexamethasone on cell death and STAT5 activation during in vitro eosinopoiesis (2003)

Glucorticoids reduce eosinophilia through a direct effect on eosinophils or indirectly on cells producing cytokines and chemokines. Conflicting data have been previously reported concerning glucocorticoid effects on eosinopoiesis. To elucidate this point, dexamethasone was added during eosinophil differentiation of CD34+ cells. Dexamethasone enhanced proliferation and differentiation through an early effect on immature cells. Dexamethasone inhibited apoptosis during early differentiation, whereas death of mature cells was increased. Signal transducer and activator of transcription 5 (STAT5) is a transcription factor involved in the proliferation, differentiation and survival of haematopoietic cells, which interacts with glucocorticoid receptor. Activation of STAT5 by interleukin-5 was investigated during eosinophil differentiation. Long isoforms of STAT5 were activated during the entire period in the culture as well as in blood eosinophils, while short isoforms were only activated during early differentiation. Short isoforms were less activated in the presence of dexamethasone. This suggests that dexamethasone could act on proliferation, differentiation and apoptosis during eosinophil differentiation through an association of STAT5 with the glucocorticoid receptor.
Inhibitors of human indoleamine 2,3‐dioxygenase identified with a target‐based screen in yeast (2006)

Indoleamine 2,3-dioxygenase (IDO) is a tryptophan degradation enzyme that is emerging as an important drug target. IDO is expressed by many human tumors to help them escape immune detection, and it has been implicated in depression and in the formation of senile nuclear cataracts. There is a need for potent and selective IDO inhibitors for use in research and as lead compounds for drug development. We show that expression of human IDO in a Saccharomyces cerevisiae tryptophan auxotroph restricts yeast growth in the presence of low tryptophan concentrations and that inhibition of IDO activity can restore growth. We use this assay to screen for IDO inhibitors in collections of pure chemicals and crude natural extracts. We identify NSC 401366 (imidodicarbonimidic diamide, N-methyl-N'-9-phenanthrenyl-, monohydrochloride) as a potent nonindolic IDO inhibitor (Ki=1.5 +/- 0.2 microM) that is competitive with respect to tryptophan. We also use this assay to identify the active compound caulerpin from a crude algal extract. The yeast growth restoration assay is simple and inexpensive. It combines desirable attributes of cell- and target-based screens and is an attractive tool for chemical biology and drug screening.
Complex of Human Apolipoprotein C-1 with Phospholipid:  Thermodynamic or Kinetic Stability? (2002)

Thermal unfolding of discoidal complexes of apolipoprotein (apo) C-1 with dimyristoyl phosphatidylcholine (DMPC) reveals a novel mechanism of lipoprotein stabilization that is based on kinetics rather than thermodynamics. Far-UV CD melting curves recorded at several heating/cooling rates from 0.047 to 1.34 K/min show hysteresis and scan rate dependence characteristic of slow nonequilibrium transitions. At slow heating rates, the apoC-1 unfolding in the complexes starts just above 25 degrees C and has an apparent melting temperature T(m) approximately 48 +/- 1.5 degrees C, close to T(m) = 51 +/- 1.5 degrees C of free protein. Thus, DMPC binding may not substantially increase the low apparent thermodynamic stability of apoC-1, DeltaG(25 degrees C) < 2 kcal/mol. The scan rate dependence of T(m) and Arrhenius analysis of the kinetic data suggest an activation enthalpy E(a) = 25 +/- 5 kcal/mol that provides the major contribution to the free energy barrier for the protein unfolding on the disk, DeltaG > or = 17 kcal/mol. Consequently, apoC-1/DMPC disks are kinetically but not thermodynamically stable. To explore the origins of this kinetic stability, we utilized dynode voltage measured in CD experiments that shows temperature-dependent contribution from UV light scattering of apoC-1/DMPC complexes (d approximately 20 nm). Correlation of CD and dynode voltage melting curves recorded at 222 nm indicates close coupling between protein unfolding and an increase in the complex size and/or lamellar structure, suggesting that the enthalpic barrier arises from transient disruption of lipid packing interactions upon disk-to-vesicle fusion. We hypothesize that a kinetic mechanism may provide a general strategy for lipoprotein stabilization that facilitates complex stability and compositional variability in the absence of high packing specificity.
CAS/Crk Coupling Serves as a “Molecular Switch” for Induction of Cell Migration (1998)

Carcinoma cells selected for their ability to migrate in vitro showed enhanced invasive properties in vivo. Associated with this induction of migration was the anchorage-dependent phosphorylation of p130CAS (Crk-associated substrate), leading to its coupling to the adaptor protein c-CrkII (Crk). In fact, expression of CAS or its adaptor protein partner Crk was sufficient to promote cell migration, and this depended on CAS tyrosine phosphorylation facilitating an SH2-mediated complex with Crk. Cytokine-stimulated cell migration was blocked by CAS lacking the Crk binding site or Crk containing a mutant SH2 domain. This migration response was characterized by CAS/Crk localization to membrane ruffles and blocked by the dominant-negative GTPase, Rac, but not Ras. Thus, CAS/Crk assembly serves as a "molecular switch" for the induction of cell migration and appears to contribute to the invasive property of tumors.
Tight regulation, modulation, and high-level expression by vectors containing the arabinose PBAD promoter (1995)

We have constructed a series of plasmid vectors (pBAD vectors) containing the PBAD promoter of the araBAD (arabinose) operon and the gene encoding the positive and negative regulator of this promoter, araC. Using the phoA gene and phoA fusions to monitor expression in these vectors, we show that the ratio of induction/repression can be 1,200-fold, compared with 50-fold for PTAC-based vectors. phoA expression can be modulated over a wide range of inducer (arabinose) concentrations and reduced to extremely low levels by the presence of glucose, which represses expression. Also, the kinetics of induction and repression are very rapid and significantly affected by the ara allele in the host strain. Thus, the use of this system which can be efficiently and rapidly turned on and off allows the study of important aspects of bacterial physiology in a very simple manner and without changes of temperature. We have exploited the tight regulation of the PBAD promoter to study the phenotypes of null mutations of essential genes and explored the use of pBAD vectors as an expression system.
Solid‐Phase Oligosaccharide Synthesis (2004)

Abstract For Abstract see ChemInform Abstract in Full Text.
Copy number variation and cytidine analogue cytotoxicity: A genome-wide association approach (2010)

These results suggest that CNVs may play a role in variation in cytidine analogue effect. Therefore, association studies of CNVs with drug response phenotypes in cell-based model systems, when paired with functional characterization, might help to identify CNV that contributes to variation in drug response.
Molecular Cloning and Characterization of a Novel Isoform of the Human UDP-Galactose Transporter, and of Related Complementary DNAs Belonging to the Nucleotide-Sugar Transporter Gene Family (1996)

We described recently the molecular cloning of human UDP-galactose transporter 1 (hUGT1) [Miura, N. et al. (1996) J. Biochem. 120, 236-241]. Now we have characterized its isoform, hUGT2, that is most likely generated through the alternative splicing of a transcript derived from the UGT genomic gene, that also codes for hUGT1. Introduction of the open reading frame sequence of hUGT2 into a mouse cell line, Had-1, that lacks the UDP-galactose transporter, complemented the genetic defect of the mutant, as judged from the lectin-sensitivity spectra of the transformants and the nucleotide-sugar transporting activity of microsomal vesicles isolated from them. UGT-related genes were found through a BLAST search of dbEST based on their significant similarity with hUGT genes. We report here cDNA clones belonging to two subfamilies of the nucleotide-sugar transporter gene family. One is the human CMP-sialic acid transporter gene, and the other is a group of homologous genes with an undefined function that are distributed in man, mouse, and rat, and show significant similarity to the yeast UDP-N-acetylglucosamine transporter.
Ammonia-Regulated Expression of a Soybean Gene Encoding Cytosolic Glutamine Synthetase in Transgenic Lotus corniculatus (1991)

Guo-Hua Miao, Bertrand Hirel, Marie C. Marsolier, Robert W. Ridge, Desh Pal S. Verma, Ammonia-Regulated Expression of a Soybean Gene Encoding Cytosolic Glutamine Synthetase in Transgenic Lotus corniculatus, The Plant Cell, Vol. 3, No. 1 (Jan., 1991), pp. 11-22