gebhart/patrepeval huggingface dataset:
Therapeutic effect of sulphated hyaluronic acid, a potential selectin‐blocking agent, on experimental progressive mesangial proliferative glomerulonephritis (2002)

The initial event in the process of leukocyte infiltration is characterized by leukocyte rolling on the surface of the endothelium, which is mediated by selectins. P- and L-selectin bind to the sulphated sugar chains of their natural ligands, including sulphated glycolipids such as sulphatide. Recently, it has been demonstrated that sulphated glycolipids and sulphated oligosaccharides interfere with selectin binding pathways. This study synthesized sulphated hyaluronic acid (SHA), which is a potential selectin-blocking agent, and examined its therapeutic effect on the experimental progressive mesangial proliferative glomerulonephritis induced by anti-Thy-1 monoclonal antibody (1-22-3 MAb) after unilateral nephrectomy. The selectin-inhibitory effect of SHA in vitro was confirmed. SHA inhibited the binding of P- and L-selectin to sulphatide, which is a glycolipid ligand for P- and L-selectin, at a concentration of 1.5 micro g/ml and 100 micro g/ml. Immunohistochemical examination showed that P-selectin was up-regulated in the glomeruli in the 1-22-3 MAb nephritis model, while the ligands for L-selectin were not detected in the glomerular tufts. A single administration of SHA ameliorated proteinuria and glomerular leukocyte infiltration in 24 h after the injection of anti-Thy-1 MAb. Anti-P-selectin MAb, but not anti-L-selectin MAb, inhibited proteinuria and glomerular leukocyte infiltration. To examine further the therapeutic effect of SHA on chronic glomerulonephritis, SHA was administered daily from day 3 to day 14 in this model. Proteinuria and glomerular leukocyte infiltration were significantly diminished in SHA-treated rats on day 14. These results suggest that SHA ameliorated rat progressive mesangial proliferative glomerulonephritis by inhibiting P-selectin-dependent leukocyte infiltration in glomeruli. Sulphated oligosaccharides may be beneficial for the therapy of mesangial proliferative glomerulonephritis.
Combined application of in vivo UV‐crosslinking and in vitro label transfer in the examination of AU‐rich sequence binding protein ‐ RNA interactions. (1995)

A combination of in vivo UV light-induced crosslinking of nucleic acids to proteins and in vitro label transfer assay was applied to investigate specific interactions between AU-rich sequences (ARE) in the 3' UTR of lymphokine mRNAs and cytoplasmic AU-rich sequence element binding proteins (AUBP) in normal human lymphoblasts and MLA 144 gibbon lymphoid tumor cells. We demonstrate that a pool of cytoplasmic AUBP can be effectively crosslinked to RNA in vivo, suggesting a close association of these proteins with ARE sequences in the cytoplasm. We also show that the UV-crosslinked AUBP pool is markedly reduced in malignantly transformed MLA 144 cells compared with normal lymphoblasts, indicating weaker interaction between lymphokine ARE and AUBP in these tumor cells. Similar differences in AUBP-RNA associations were found between the membrane-bound polysomal subfractions of the two cell types where most of the AUBP activity was localized. We suggest that the decreased AUBP-mRNA association in MLA 144 cells might reflect a process concerned with disturbances of mRNA metabolism in the neoplastic phenotype.
Tumor Development by Transgenic Expression of a Constitutively Active Insulin-Like Growth Factor I Receptor (2005)

The insulin-like growth factor I receptor (IGF-IR) is a transmembrane tyrosine kinase that is essential to growth and development and also thought to provide a survival signal for the maintenance of the transformed phenotype. There has been increasing interest in further understanding the role of IGF-I signaling in cancer and in developing receptor antagonists for therapeutic application. We describe herein a novel animal model that involves transgenic expression of a fusion receptor that is constitutively activated by homodimerization. Transgenic mice that expressed the activated receptor showed aberrant development of the mammary glands and developed salivary and mammary adenocarcinomas as early as 8 weeks of age. Xenograft tumors and a cell line were derived from the transgenic animals and are sensitive to inhibition by a novel small-molecule inhibitor of the IGF-IR kinase. This new model should provide new opportunities for further understanding how aberrant IGF-IR signaling leads to tumorigenesis and for optimizing novel antagonists of the receptor kinase.
Coordinate control of syntheses of ribosomal ribonucleic acid and ribosomal proteins during nutritional shift-up in Saccharomyces cerevisiae. (1981)

We investigated the regulation of ribosome synthesis in Saccharomyces cerevisiae growing at different rates and in response to a growth stimulus. The ribosome content and the rates of synthesis of ribosomal ribonucleic acid and of ribosomal proteins were compared in cultures growing in minimal medium with either glucose or ethanol as a carbon source. The results demonstrated that ribosome content is proportional to growth rate. Moreover, these steady-state concentrations are regulated at the level of synthesis of ribosomal precursor ribonucleic acid and of ribosomal proteins. When cultures growing on ethanol were enriched with glucose, the rate of ribosomal ribonucleic acid synthesis, measured by pulsing cells with [methyl-3H]methionine, increased by 40% within 5 min, doubled within 15 min, and reached a steady state characteristic of the new growth medium by 30 min. Labeling with [3H]leucine reveal a coordinate increase in the rate of synthesis of 30 or more ribosomal proteins as compared with that of total cellular proteins. Their synthesis was stimulated approximately 2.5-fold within 15 min and nearly 4-fold within 60 min. The data suggest that S. cerevisiae responds to a growth stimulus by preferential stimulation of the synthesis of ribosomal ribonucleic acid and ribosomal proteins.
A Novel β-Galactoside-Binding Lectin in Adult Rat Kidney1 (1994)

Two carbohydrate-binding proteins with subunit molecular weight of about 17,500 and 16,500, respectively, were isolated from Triton X-100 extracts of rat kidney using a lactose affinity column. They did not require Ca2+ for the carbohydrate-binding nor reducing agents for maintaining their activity. The partial amino acid sequence of the 17.5-kDa protein (rkCBP-17.5), the main component, revealed that this protein is a novel member of a superfamily of beta-galactoside-binding animal lectins. The N-terminal amino acid sequence of the 16.5 kDa component (rkCBP-16.5) indicated that it is a fragment derived from the IgE-binding protein (IgEBP). Monoclonal antibodies to rkCBP-17.5 were prepared and used to examine the distribution of the lectin in various organs of adult rats. Immunoreactive protein with the same molecular weight was found in lung, spleen and liver, in lesser amounts in heart, and in trace amounts in brain and skeletal muscle. rkCBP-17.5 exhibits binding activity to various saccharides with the following order of affinity: N-acetyllactosamine > lactose > D-galactose > methyl alpha-D-galactopyranoside > N-acetyl-D-galactosamine > methyl beta-D-galactopyranoside. It binds to Engelbreth-Holm-Swarm(EHS) tumor laminin and rat plasma fibronectin, but does not bind to human plasma fibronectin.
Structure-Function Analysis of Bcl-2 Protein (1995)

The Bcl-2 protein is a suppressor of programmed cell death that homodimerizes with itself and forms heterodimers with a homologous protein Bax, a promoter of cell death. Expression of Bax in Saccharomyces cerevisiae as a membrane-bound fusion protein results in a lethal phenotype that is suppressible by co-expression of Bcl-2. Functional analysis of deletion mutants of human Bcl-2 in yeast demonstrated the presence of at least three conserved domains that are required to suppress Bax-mediated cytotoxicity, termed domains A (amino acids 11-33), B (amino acids 138-154), and C (amino acids 188-196). In vitro binding experiments using GST-Bcl-2 fusion proteins demonstrated that Bcl-2(delta B) and Bcl-2(delta C) deletion mutants had a markedly impaired ability to heterodimerize with Bax but retained the ability to homodimerize with wild-type Bcl-2. In contrast, Bcl-2(delta A) and an NH2-terminal deletion mutant Bcl-2(delta 1-82) retained Bax binding activity in vitro but failed to suppress Bax-mediated cytotoxicity in yeast. Sequences downstream of domain C in the region 197-218 also were shown to be required for Bax-binding in vitro and anti-death function in yeast. Analysis of Bcl-2/Bcl-2 homodimerization using both in vitro binding assays as well as a yeast two-hybrid method provided evidence in support of a head-to-tail model for Bcl-2/Bcl-2 homodimerization and revealed that sequences within the NH2-terminal A domain interact with a structure that requires the presence of both the carboxyl B and C domains in combination. In addition to further delineating structural features within Bcl-2 that are required for homo-dimerization, the findings reported here support the hypothesis that Bcl-2 promotes cell survival by binding directly to Bax but suggest that ability to bind Bax can be insufficient for anti-cell death function.
MALAT‐1 enhances cell motility of lung adenocarcinoma cells by influencing the expression of motility‐related genes (2010)

MALAT‐1, a long non‐coding RNA, is associated with metastasis, but its role in the metastatic process remains unknown. Here, we show that short‐interfering RNA‐mediated MALAT‐1 silencing impaired in vitro cell motility of lung cancer cells and influenced the expression of numerous genes. In these genes, knockdown of any one of CTHRC1 , CCT4 , HMMR , or ROD1 clearly inhibited cell migration. In MALAT‐1 knockdown cells, pre‐mRNA levels were decreased in some but not all genes. Thus, our findings suggest that MALAT‐1 is a novel class of non‐coding RNA that promotes cell motility through transcriptional and post‐transcriptional regulation of motility related gene expression.
Gene Expression Changes and Early Events in Cotton Fibre Development (2007)

Recent advances in gene expression studies are beginning to provide new insights into a better understanding of early events in cotton fibre development. Fibre cell development is a complex process involving many pathways, including various signal transduction and transcriptional regulation components. Several analyses using expressed sequence tags and microarray have identified transcripts that preferentially accumulate during fibre development. These studies, as well as complementation and overexpression experiments using cotton genes in arabidopsis and tobacco, indicate some similar molecular events between trichome development from the leaf epidermis and fibre development from the ovule epidermis. Specifically, MYB transcription factors regulate leaf trichome development in arabidopsis and may regulate seed trichome development in cotton. In addition, transcript profiling and ovule culture experiments both indicate that several phytohormones and other signalling pathways mediate cotton fibre development. Auxin and gibberellins promote early stages of fibre initiation; ethylene- and brassinosteroid-related genes are up-regulated during the fibre elongation phase; and genes associated with calmodulin and calmodulin-binding proteins are up-regulated in fibre initials. Additional genomic data, mutant and functional analyses, and genome mapping studies promise to reveal the critical factors mediating cotton fibre cell development.
Effects of Testosterone Replacement in Hypogonadal Men1 (2000)

Treatment of hypogonadal men with testosterone has been shown to ameliorate the effects of testosterone deficiency on bone, muscle, erythropoiesis, and the prostate. Most previous studies, however, have employed somewhat pharmacological doses of testosterone esters, which could result in exaggerated effects, and/or have been of relatively short duration or employed previously treated men, which could result in dampened effects. The goal of this study was to determine the magnitude and time course of the effects of physiological testosterone replacement for 3 yr on bone density, muscle mass and strength, erythropoiesis, prostate volume, energy, sexual function, and lipids in previously untreated hypogonadal men. We selected 18 men who were hypogonadal (mean serum testosterone +/- SD, 78 +/- 77 ng/dL; 2.7 +/- 2.7 nmol/L) due to organic disease and had never previously been treated for hypogonadism. We treated them with testosterone transdermally for 3 yr. Sixteen men completed 12 months of the protocol, and 14 men completed 36 months. The mean serum testosterone concentration reached the normal range by 3 months of treatment and remained there for the duration of treatment. Bone mineral density of the lumbar spine (L2-L4) increased by 7.7 +/- 7.6% (P < 0.001), and that of the femoral trochanter increased by 4.0 +/- 5.4% (P = 0.02); both reached maximum values by 24 months. Fat-free mass increased 3.1 kg (P = 0.004), and fat-free mass of the arms and legs individually increased, principally within the first 6 months. The decrease in fat mass was not statistically significant. Strength of knee flexion and extension did not change. Hematocrit increased dramatically, from mildly anemic (38.0 +/- 3.0%) to midnormal (43.1 +/- 4.0%; P = 0.002) within 3 months, and remained at that level for the duration of treatment. Prostate volume also increased dramatically, from subnormal (12.0 +/- 6.0 mL) before treatment to normal (22.4 +/- 8.4 mL; P = 0.004), principally during the first 6 months. Self-reported sense of energy (49 +/- 19% to 66 +/- 24%; P = 0.01) and sexual function (24 +/- 20% to 66 +/- 24%; P < 0.001) also increased, principally within the first 3 months. Lipids did not change. We conclude from this study that replacing testosterone in hypogonadal men increases bone mineral density of the spine and hip, fat-free mass, prostate volume, erythropoiesis, energy, and sexual function. The full effect of testosterone on bone mineral density took 24 months, but the full effects on the other tissues took only 3-6 months. These results provide the basis for monitoring the magnitude and the time course of the effects of testosterone replacement in hypogonadal men.
Effect of interferon-alpha (IFN alpha) on various human tumor xenografts. (1988)

The growth of some human tumor xenografts (3 out of 8, melanoma, non-Hodgkin's lymphoma, squamous cell carcinoma) was successfully--but moderately and temporarily--inhibited, when interferon-alpha (EGIS, Hungary) was given for 10 days. The route of administration (intratumoral or intraperitoneal) was usually not a decisive factor. An attempt to potentiate IFNa action with Zymozan or Cyclophosphamide did not succeed.
Measuring the encapsulation of cosmetic ingredients into liposomes : A method for large, hydrophilic compounds (1996)

Encapsulation efficiency (EE) is an important parameter for the characterization of liposome systems en-trapping hydrophilic compounds. In this study, we were interested in quantifying EE of inulin, a 5,000-Da polysaccharide molecule, in various phospholipid liposome systems. Methods to separate free from encap-sulated inulin were evaluated. Dialysis and the centrifuged-column method were not appropriate for our liposome systems. Conversely, the Ficoll © discontinuous density gradient method was found to be an excellent tool for separating inulin encapsulated in large, multilamellar liposome preparations from free inulin. Using this method, we found that EE values approaching 40 % were obtained by the reverse-phase evaporation method, regardless of cholesterol evel. The microstructure was shown to consist of large heterogeneous multilamellar vesicles with diameters of 2-20 lam. At equal lipid concentration, much lower EE values (ca. 4%) were obtained for liposomes prepared by the film method. For inulin, comparison with other studies shows that EEs should be measured rather than inferred from systems having different compositions or preparation methods.
TRISS METHODOLOGY IN PENETRATING TRAUMA: 198 PATIENTS AT BARAGWANATH HOSPITAL (1993)

TRISS methodology is a statistical technique by which the probability of survival in injury can be estimated. It combines an anatomical index of injury severity (the injury severity score, ISS), a physiological index (the revised trauma score, RTS), age and the mechanism of injury. In this study TRISS was used to assess 198 patients with penetrating injury at Baragwanath Hospital. One hundred and sixty-two patients had stab wounds, 26 gunshot wounds, and 10 received other injuries. Fifty patients were seriously injured (ISS > 15). Four patients (2%) died. The respective probabilities of survival for these four patients, as derived by TRISS, were 0%, 0%, 6% and 46%. TRISS demonstrated that the outcome of the patients as a group was comparable to other centres. TRISS is a useful method for monitoring the effectiveness of a trauma unit and objectively identifying cases for peer review.
Temporal Trends of Opportunistic Infections and Malignancies in Homosexual Men with AIDS (1994)

Temporal changes in the lifetime occurrence of opportunistic infections and malignancies among 1115 homosexual men diagnosed with AIDS were examined. Information from the AIDS surveillance registry, hospital pathology and microbiology logs, patient chart reviews, cancer registries, and death certificates was used to calculate the frequency of specific opportunistic infections and malignancies as lifetime (initial or subsequent) diagnoses. The most common lifetime diagnoses were Pneumocystis carinii pneumonia (PCP; 66.5%), Kaposi's sarcoma (KS; 50.7%), disseminated Mycobacterium avium complex (DMAC) infection (29.6%), and cytomegalovirus (CMV) infection (19.6%). From 1981 to 1990, there was a significant decrease in the rate of KS (P = .003) and a significant increase in the rate of DMAC infection (P = .03). PCP decreased during 1985-1990 (P = .009), while CMV infection increased from 1987 through 1990 (P = .03). Thus, KS and PCP have declined over time, while DMAC and CMV are causing substantial and increasing morbidity among AIDS patients.
Regulation of icaR gene expression in Staphylococcus epidermidis (2002)

LightCycler and conventional reverse transcription-polymerase chain reaction (RT-PCR) were used to examine regulation of icaR, which encodes a repressor of the Staphylococcus epidermidis ica operon. Varying concentrations of NaCl and ethanol activated ica but only high levels of both compounds repressed icaR transcription. Activation of ica by subinhibitory concentrations of tetracycline, which was strain-dependent, was also associated with icaR repression. In an icaR: :Em mutant, NaCl but not ethanol activated ica whereas both compounds repressed icaR expression indicating that environmental regulation of the icaR gene is IcaR-independent. Apparently ethanol signals exclusively through IcaR to activate ica and regulates IcaR at the transcriptional and posttranscriptional levels. NaCl also regulates icaR expression but in addition can activate ica via an icaR-independent pathway.
Chitotriosidase and YKL‐40 in normal and pre‐eclamptic pregnancies (2007)

This study may be the first to demonstrate maternal and fetal macrophage activation in pre-eclampsia.
Ten-year outcome of tardive dyskinesia (1994)

The data of this 10-year follow-up study provide evidence for the long-term stability of tardive dyskinesia and for the feasibility of maintenance neuroleptic therapy for chronic psychotic patients who have tardive dyskinesia.
mRNA Transfection of CXCR4-GFP Fusion—Simply Generated by PCR—Results in Efficient Migration of Primary Human Mesenchymal Stem Cells (2008)

We present a general, entirely PCR-based strategy to construct mRNAs coding for green fluorescent protein (GFP) fusion proteins from a cDNA pool. We exemplify our approach for the chemokine receptor CXCR4. mRNA transfection of the PCR-generated fusion of CXCR4-GFP into K562 cells or primary mesenchymal stem cells (MSCs) resulted in excellent viability (> 90%) with more than 90% of target cells expressing easily detectable CXCR4-GFP for > 72 h. The fusion protein was localized in the plasma membrane and was rapidly internalized upon incubation with the CXCR4 ligand stromal cell-derived factor-1 (SDF-1). Transwell migration experiments showed significantly increased migration of CXCR4-GFP mRNA-transfected MSCs toward a gradient of SDF-1, demonstrating that mRNA-mediated chemokine receptor overexpression allows for transient initiation of chemotaxis. The presented strategy to construct a PCR-based fluorescent fusion protein can be generally applied to other genes of interest to study their function by simple overexpression and easy detection in primary cells.
A cluster of three genes (dapA, orf2, and dapB) of Brevibacterium lactofermentum encodes dihydrodipicolinate synthase, dihydrodipicolinate reductase, and a third polypeptide of unknown function (1993)

The dapA and dapB genes, encoding, respectively, dihydrodipicolinate synthase and dihydrodipicolinate reductase, the two first enzymes of the lysine branch of the aspartic amino acid family, were cloned from the DNA of the amino acid-producing bacterium Brevibacterium lactofermentum. The two genes were clustered in a 3.5-kb Sau3AI-BamHI fragment but were separated by an open reading frame of 750 nucleotides. The protein encoded by this open reading frame had little similarity to any protein in the data banks, and its function remains unknown. The three genes were translated in Escherichia coli, giving the corresponding polypeptides.
Differential expression of 10 sigma factor genes in Mycobacterium tuberculosis (1999)

The ability of Mycobacterium tuberculosis to adapt to different environments in the infected host is essential for its pathogenicity. Consequently, this organism must be able to modulate gene expression to respond to the changing conditions it encounters during infection. In this paper we begin a comprehensive study of M. tuberculosis gene regulation, characterizing the transcript levels of 10 of its 13 putative sigma factor genes. We developed a real-time RT-PCR assay using a family of novel fluorescent probes called molecular beacons to quantitatively measure the different mRNAs. Three sigma factor genes were identified that have increased mRNA levels after heat shock, two of which also responded to detergent stress. In addition, we also identified a sigma factor gene whose mRNA increased after mild cold shock and a second that responded to conditions of low aeration.
Restricted ketogenic diet enhances the therapeutic action of N‐butyldeoxynojirimycin towards brain GM2 accumulation in adult Sandhoff disease mice (2010)

Sandhoff disease is an autosomal recessive, neurodegenerative disease involving the storage of brain ganglioside GM2 and asialo-GM2. Previous studies showed that caloric restriction, which augments longevity, and N-butyldeoxynojirimycin (NB-DNJ, Miglustat), an imino sugar that hinders the glucosyltransferase catalyzing the first step in glycosphingolipid biosynthesis, both increase longevity and improve motor behavior in the beta-hexosaminidase (Hexb) knockout (-/-) murine model of Sandhoff disease. In this study, we used a restricted ketogenic diet (KD-R) and NB-DNJ to combat ganglioside accumulation. Adult Hexb-/- mice were placed into one of the following groups: (i) a standard diet (SD), (ii) a SD with NB-DNJ (SD + NB-DNJ), (iii) a KD-R, and (iv) a KD-R with NB-DNJ (KD-R + NB-DNJ). Forebrain GM2 content (mug sialic acid/100 mg dry wt) in the four groups was 375 +/- 15, 312 +/- 8, 340 +/- 28, and 279 +/- 26, respectively, indicating an additive interaction between NB-DNJ and the KD-R. Most interestingly, brain NB-DNJ content was 3.5-fold greater in the KD-R + NB-DNJ mice than in the SD + NB-DNJ mice. These data suggest that the KD-R and NB-DNJ may be a potential combinatorial therapy for Sandhoff disease by enhancing NB-DNJ delivery to the brain and may allow lower dosing to achieve the same degree of efficacy as high dose monotherapy.