gebhart/patrepeval huggingface dataset:
Characterization of Mouse Cathepsin K Gene, the Gene Promoter, and the Gene Expression (1999)

Cathepsin K, a lysosomal cysteine protease, is abundantly and selectively expressed in osteoclasts and has a specialized role in osteoclast-mediated bone resorption. In contrast to function studies, transcription regulation of cathepsin K remains largely unknown. In this study, the gene encoding mouse cathepsin K and the promoter have been isolated and completely sequenced. In addition, the temporal and spatial expressions of cathepsin K have been characterized. Intrachromosomal mapping studies revealed that the gene contains eight exons and seven introns spanning approximately 10.6 kb of genomic DNA, a genomic organization that was highly conserved with respect to its human homology. Analysis of the 9 kb 5' flanking region indicates that this gene lacks canonical TATA and CAAT boxes and contains multiple putative transcription regulatory elements which are also present in the comparable position of 5' flanking region of human cathepsin K gene. Mouse cathepsin K was found to be a single-copy gene. Northern blot analysis of RNAs from a number of mouse tissues revealed that cathepsin K mRNA is selectively expressed in osteoclast. The selective expression of cathepsin K was confirmed by anticathepsin K immunohistochemical staining. The sequence of cathepsin K expression was linked to osteoclast differentiation in vivo and in vitro by a tartrate-resistant acid phosphatase-anticathepsin K dual immunostaining technique. Cathepsin K is initially expressed at the preosteoclast stage and throughout the mature osteoclast stage. The primer extension assay indicated a major transcription start site 58 bp upstream of the initiator Met codon. The characterization of the cathepsin K gene, its promoter, and the temporal and spatial expression may provide valuable insights into its osteoclast-specific expression and the molecular mechanisms responsible for osteoclast activation.
Functional GIP Receptors Are Present on Adipocytes (1998)

In addition to its important role in maintaining glucose homeostasis, it has recently become apparent that glucose-dependent insulinotropic polypeptide (GIP) is also involved in different steps of lipid metabolism. GIP has been shown to stimulate the release of lipoprotein lipase from fat, as well as increase the rate of fat incorporation into adipose tissue. Moreover, GIP has been shown to increase the clearance rate of chylomicrons in the circulation and to inhibit the action of glucagon. Despite evidence for GIP effects on fat tissue, GIP receptors have not been identified in fat cells or tissues. The present study was undertaken to identify GIP receptors in isolated adipocytes, as well as to identify GIP receptors in the established fat cell line, differentiated 3T3-L1. RNAse protection analysis demonstrated the presence of GIP receptor transcripts in rat adipocytes. A polyclonal GIP receptor antiserum directed at the N-terminus of the receptor detected the presence of GIP receptors in both rat fat and differentiated 3T3-L1 cells by Western blot analysis. Moreover, [125I] GIP binding assays revealed both specific and displaceable GIP binding sites in differentiated 3T3-L1 cells (IC50 = 10(-9) M). When undifferentiated 3T3-L1 cells, which appear to express relatively few GIP receptors, were incubated in the presence of GIP, no effect on intracellular cAMP accumulation was detected. In contrast, the inclusion of 10 nM GIP in the incubation medium increased cAMP accumulation in rat fat cells and differentiated 3T3-L1 cells. This increase in cAMP accumulation was abolished with the specific GIP receptor antagonist GIP(7-30)NH2. The results of these studies indicate that GIP receptors are present in fat cells and are up-regulated when 3T3-L1 cells undergo differentiation to become adipocytes. Furthermore, the increase in intracellular cAMP accumulation detected upon ligand binding indicates that these receptors are functional.
Primary structure and cell-type specific expression of a gustatory G protein-coupled receptor related to olfactory receptors (1993)

We have reported on the partial structures of a multigene family encoding GTP-binding protein (G protein)-coupled, seven-transmembrane receptors expressed in the tongue (Abe, K., Kusakabe, Y., Tanemura, K., Emori, Y., and Arai, S. (1993) FEBS Lett. 316, 253-256). Here we describe a full-length cDNA clone encoding a tongue cell-type specific receptor. The encoded protein consists of 312 amino acid residues. In overall structure, the protein is similar to known G protein-coupled, seven-transmembrane receptors such as an olfactory receptor (56% identity) but is significantly different in part, particularly in NH2-terminal extracellular and COOH-terminal cytoplasmic domain structures. Northern analysis showed that the mRNA for this protein is expressed only in the epithelium of the tongue, not in other organs. In situ hybridization experiments clearly indicated that the mRNA is expressed exclusively on the tongue apical surface, not on the reverse side of the tongue nor in its muscle layer. Expression was also detected in the taste buds and surrounding cellular tissues of the fungiform and circumvallate papillae. It is suggested that this gustatory receptor structurally related to olfactory receptors may be a candidate for a taste receptor.
Attention Deficit Disorder (1985)

In the article by Eichlseder (Pediatrics 1985;76:176-184), a practicing pediatrician in West Germany, reviews 1,000 cases of attention deficit disorder seen in his office practice during a 10-year period. Such a report is intriguing, not only because of the author's sincerity and diligence in caring for this population, but also because his involvement may serve as a potential model for the kind of clinical studies that practicing pediatricians elsewhere might be encouraged to undertake. However, if other practicing pediatricians are to emulate Eichlseder, they need to pay careful attention to methodologic details if their observations are to be meaningful. The following comments we hope will serve as a gentle reminder of some of the pitfalls in clinical research in attention deficit disorder.
Dendritic cells break tolerance and induce protective immunity against a melanocyte differentiation antigen in an autologous melanoma model. (2000)

Tyrosinase-related protein (TRP) 2 belongs to the melanocyte differentiation antigens and has been implicated as a target for immunotherapy of human as well as murine melanoma. In the current report, we explored the efficacy of nonmutated epitopes with differential binding affinity for MHC class I, derived from mouse TRP2 to induce CTL-mediated, tumor-reactive immunity in vivo within the established B16 melanoma model of C57BL/6 mice. The use of nonmutated TRP2-derived epitopes for vaccination provides a mouse model that closely mimics human melanoma without introduction of xenogeneic or otherwise foreign antigen. The results demonstrate that vaccination with TRP2 peptide-loaded bone marrow-derived dendritic cells (DCs) results in activation of high avidity TRP2-specific CTLs, displaying lytic activity against both B16 melanoma cells and normal melanocytes in vitro. In vivo, protective antitumor immunity against a lethal s.c. B16 challenge was observed upon DC-based vaccination in this fully autologous tumor model. The level of protective immunity positively correlated with the MHC class I binding capacity of the peptides used for vaccination. In contrast, within this autologous model, vaccination with TRP2 peptide in Freund's adjuvant or TRP2-encoding plasmid DNA did not result in protective immunity against B16. Strikingly, despite the observed CTL-mediated melanocyte destruction in vitro, melanocyte destruction in vivo was sporadic and primarily restricted to minor depigmentation of the vaccination site. These results emphasize the potency of DC-based vaccines to induce immunity against autologous tumor-associated antigen and indicate that CTL-mediated antitumor immunity can proceed without development of adverse autoimmunity against normal tissue.
Seizure characteristics in chromosome 20 benign familial neonatal convulsions (1993)

We studied a kindred of 69 affected individuals with the autosomal dominant epileptic syndrome of benign familial neonatal convulsions, linked to chromosome 20. Forty-two percent had their seizure onset on day 3, while remission took place in 68% during the first 6 weeks. Seizures were brief and the phenotype was of a mixed seizure type, starting with tonic posture, ocular symptoms, apnea, and other autonomic features. The seizure often progressed to clonic movements and motor automatisms. The postictal state was brief, and interictally the neonates looked well. The ictal EEG pattern with generalized suppression of amplitude on onset may be relatively unique. Neurocognitive outcome was usually normal, but the risk for subsequent epilepsy was 16%. Most of the later epilepsy was generalized tonic or tonic-clonic, and some seizures were provoked, raising the possibility of an unusual form of reflex epilepsy.
Impaired Function of Bipolar Cells in the Royal College of Surgeons Rat (1998)

The retina of the Royal College of Surgeons (RCS) strain of rat, which is being used as an animal model for human retinal degenerations, has been employed in the study of the function of second order neurons. By about the 33rd postnatal day the dendritic branching of isolated bipolar cells is more sparse than in bipolar cells of the normal rat retina, but their GABA channels are as in the normal rat retina. The normally occurring light-induced distal potassium increase has been used as the indicator of the functional competence of second order neurons in the isolated RCS rat retina. These are dependent upon the integrity of ionotropic and metabotropic synapses. At about the 22nd postnatal day MgCl2 enlarges the light-induced distal potassium increase in the young RCS rat retina as in the normal rat retina. It seems that MgCl2 does not block the metabotropic synapses of on-bipolar cells. At about postnatal day 33, at which time the photoreceptors of the RCS rat retina had become severely damaged, the size of this light-induced distal potassium increase was not changed, but it was abolished by MgCl2. This indicates that bipolar cells are still active but that the synaptic function of on-bipolar cells has become vulnerable to MgCl2. The conclusion is that at a time when photoreceptor degeneration is already severe bipolar cells are still active, but that on-bipolars, mainly rod bipolar cells, have some functional deficit.
Long-Term Use of Bisphosphonates in Osteoporosis (2010)

Bisphosphonates are popular and effective for treatment of osteoporosis. Because they accumulate in bone and provide some residual antifracture reduction when treatment is stopped, we recommend a drug holiday after 5-10 yr of bisphosphonate treatment. The duration of treatment and length of the holiday are based on fracture risk and pharmacokinetics of the bisphosphonate used. Patients at mild risk might stop treatment after 5 yr and remain off as long as bone mineral density is stable and no fractures occur. Higher risk patients should be treated for 10 yr, have a holiday of no more than a year or two, and perhaps be on a nonbisphosphonate treatment during that time.
Purification of recombinant Helicobacter pylori urease apoenzyme encoded by ureA and ureB (1992)

Helicobacter pylori, a gram-negative, microaerophilic, spiral-shaped bacterium, is an etiologic agent of human gastritis and peptic ulceration and is highly restricted to the gastric mucosa of humans. Urease, synthesized at up to 6% of the soluble cell protein, hydrolyzes urea, thereby releasing ammonia, which may neutralize acid, allowing survival of the bacterium and initial colonization of the gastric mucosa. The urease protein is encoded by two subunit genes, ureA and ureB; however, accessory genes are necessary for enzyme activity. H. pylori urease genes were isolated from a cosmid gene bank and subcloned on a 5.8-kb Sau3A partial fragment carrying ureCDAB, corresponding to four open reading frames described by A. Labigne, V. Cussac, and P. Courcoux (J. Bacteriol. 173:1920-1931, 1991). Clones were confirmed as ureas gene sequences by polymerase chain reaction amplification. The recombinant enzyme was purified from the soluble protein of French press lysates of Escherichia coli DH5 alpha(pHP402) by chromatography on DEAE-Sepharose, Phenyl-Sepharose, Mono-Q, and Superose 6 resins. Fractions containing a catalytically inactive apoenzyme were identified by an enzyme-linked immunosorbent assay (ELISA) by using antisera to native UreA (29.5 kDa) and UreB (66 kDa). Purified recombinant urease was indistinguishable from native enzyme on a Superose 6 column and on Coomassie blue-stained sodium dodecyl sulfate-polyacrylamide gels. The protein reacted specifically on Western blots (immunoblots) with anti-UreA and anti-UreB antibodies and was recognized with an intensity equal to that of the native enzyme in an ELISA using human sera. Clones containing only ureA and ureB also produced an assembled but inactive enzyme. Enzyme activity was not restored by in trans complementation with cloned urease accessory gene sequences from Proteus mirabilis or Morganella morganii. H. pylori urease genes (ureCDAB) subcloned into pACYC184 were also not complemented with any of 1,000 cosmid clones containing H. pylori chromosomal sequences. However, larger clones containing 4.5 kb of DNA downstream of ureB synthesized catalytically active urease when grown in minimal medium. These data indicate that the ureA and ureB genes encoding H. pylori urease are transcribed and translated in E. coli and that these genes alone are sufficient for the synthesis and assembly of the native size enzyme. Genes downstream of ureB, however, are necessary for production of a catalytically active urease.
Characterization of proton transport in bone-derived membrane vesicles. (1992)

ATP-dependent proton transport was characterized in membrane vesicles, prepared by differential centrifugation from medullary bone of egg laying hens, a source rich in osteoclasts. The H(+)-ATPase present in this preparation showed the characteristics of a vacuolar H(+)-ATPase in its sensitivity to inhibitors, including bafilomycin A1, its sensitivity to cold treatment and its electrogenic mechanism. There was no evidence for a direct activation of the H(+)-ATPase by anions, including Cl-. These results are consistent with the view that the osteoclast, the cell responsible for bone resorption, secrets acid by means of a vacuolar H(+)-ATPase.
Integrins and tumor cell dissemination. (1989)

The ability of a tumor cell to metastasize is determined, in part, by its adhesive interactions with other cells and with components of the extracellular matrix. An ever-expanding family of cell surface receptors, the integrins, is an essential player in these interactions. Research efforts aimed at understanding the precise role of individual integrins in normal and transformed cells may offer a general framework for future therapeutic approaches. Here we review recent progress toward this goal.
In situ detection of neoplastic transformation and chemopreventive effects in rat esophagus epithelium using angle-resolved low-coherence interferometry. (2003)

We present a quantitative study of the nuclear morphometry of epithelial cells in an animal model of esophageal carcinogenesis. Changes in the size and texture of cell nuclei as a result of neoplastic transformation and chemopreventive action are observed in situ using a new optical technique, angle-resolved low-coherence interferometry (a/LCI). The capabilities of a/LCI are demonstrated via quantitative in situ measurements of the nuclear morphometry of basal epithelial cells, approximately 50-100 microm beneath the tissue surface without the need for exogenous contrast agents or tissue fixation. The measurements quantify changes in nuclear size, characterized by average diameter, and nuclear texture, characterized by fractal dimension of the subcellular structures. Using this technique, we observed changes in the morphometry of rat esophageal epithelial cells in response to treatment with the carcinogen N-nitrosomethylbenzylamine. In addition, morphometric changes were observed in the esophagi of rats treated with N-nitrosomethylbenzylamine and two chemopreventive agents, difluoromethylornithine and perillyl alcohol. These agents induced either apoptosis in the basal epithelium (difluoromethylornithine) or both apoptosis and vacuolation of basal epithelial cells (perillyl alcohol). Vacuolation was associated with cellular toxicity. The light-scattering measurements were compared with histological images of the same tissues. The potential of a/LCI as a noninvasive means to investigate the development of epithelial neoplasia and for tracking the efficacy of chemopreventive agents appears high. This technique also may provide a new screening tool for intraepithelial neoplasia.
Real-Time Measurement of Travel Time Delay in Work Zones and Evaluation Metrics Using Bluetooth Probe Tracking (2010)

This paper describes the collection and use of 1.4 million travel time records that were collected over a 12-week period in 2009 to evaluate and communicate quantifiable travel mobility metrics for a rural interstate highway work zone along I-65 in northwestern Indiana. The effort involved the automated collection and processing of Bluetooth probe data from multiple field collection sites, communicating travel delay times to the motoring public, assessing driver diversion rates, and developing proposed metrics for a state transportation agency to evaluate work zone mobility performance. Collected travel time profiles were compared with traditionally measured hourly flows in both incident and nonincident conditions. Through the 12-week period over which work zone performance was measured, the work zone had 422 h of congested conditions in which travel time delay was greater than 10 min. Despite the display of real-time delay measurements to the motoring public through portable dynamic message signs, a negligible percentage of the travel probes were observed to divert in advance of the congested work zone through self-guidance. Implementation of a targeted alternate route starting the weekend of July 24 resulted in an increase of observed probes diverting along the trail-blazed route from none to more than 30%. The paper concludes by suggesting that acquisition of work zone travel time data provides a mechanism for assessing the relationship between crashes and work zone queuing. Real-time monitoring of these travel time data may also enable future contracts to include innovative travel time reliability clauses.
Popliteal Sciatic Nerve Block for Postoperative Analgesia (1996)

Eighty-six patients were evaluated prospectively following the placement of a sciatic nerve block in the popliteal fossa after a major foot or ankle operation. Needle placement was guided by a peripheral nerve stimulator and 30 ml of 0.5% bupivacaine with epinephrine was used. Ninety-seven percent of patients had a successful block. Only one patient had severe discomfort during the block placement. The block lasted an average of 20 hours. During the first 24 hours after surgery, patients took an average of three hydrocodone tablets. Twenty-two of the 23 patients who had had previous major foot or ankle surgery found that the block was better than their previous pain control regimen. No patient had complications related to the block and 95% were satisfied and would have the block again.
Characterization of three non‐peptide endothelin receptor ligands using human cloned ETA and ETB receptors (1994)

1. A number of putative endothelin (ET) receptor ligands were synthesized with a view to assessing their relative affinity for human recombinant ET receptors. 2. Human (h) and endothelin ETA and ETB receptor open reading frames were cloned by reverse transcription-polymerase chain reaction into the mammalian expression vector pcDNA1 and stable cell lines were created by transfection of Chinese hamster ovary cells. 3. Scatchard analyses of saturation isotherms for the specific binding of [125I]-endothelin-1 ([125I]-ET-1) to membranes, prepared from Chinese hamster ovary cells transfected with hETA or hETB receptors, yielded values for equilibrium dissociation constants (Kd) of 20.5 +/- 1.8 pM and 25.5 +/- 5.5 pM, respectively. Hill coefficients did not differ significantly from unity, suggesting binding to homogeneous, non-interacting receptor populations. 4. Pharmacological characterization of the transfected hETA and hETB receptors was undertaken by measuring the relative abilities of ETA and ETB receptor-selective peptide ligands to inhibit binding of [125I]ET-1. For interaction with hETA receptors, the relative order of potency was ET-1 > ET-3 = FR139317 = BQ123 >[Ala1,3,11,15]-ET-1 = sarafotoxin S6c (S6c). In contrast, the relative order of potency, at hETB receptors, was ET-1 = ET-3 = [Ala1,3,11,15]-ET-1 = S6c >> FR139317 = BQ123. 5. The novel non-peptide ligands, Ro 46-2005, SB 209670 and BMS 182874, were found to inhibit [125I]-ET-1 binding to human recombinant ETA and ETB receptors. At hETA receptors, the calculated pIC50 values were 6.7 (Ro 46-2005), 8.7 (SB 209670) and 5.8 (BMS 182874), while at hETB receptors, the corresponding pIC50 values were 6.8, 7.5 and <5, respectively.6. In conclusion, we have characterized the pharmacology of human cloned ETA and ETB receptors and used these in membrane binding assays to determine the affinity and selectivity of three structurally diverse non-peptide ET receptor ligands. SB 209670 is, to date, the highest affinity non-peptide ligand to be described for ET receptors. As such, it may prove to be a valuable tool in further examination of the physiological and pathophysiological roles of endothelins.
Stochastic stability of the discrete-time extended Kalman filter (1999)

The authors analyze the error behavior for the discrete-time extended Kalman filter for general nonlinear systems in a stochastic framework. In particular, it is shown that the estimation error remains bounded if the system satisfies the nonlinear observability rank condition and the initial estimation error as well as the disturbing noise terms are small enough. This result is verified by numerical simulations for an example system.
Detection of the Philadelphia chromosome in acute lymphoblastic leukemia by pulsed-field gel electrophoresis (1989)

The Philadelphia (Ph1) chromosome is an acquired abnormality in the malignant cells of 10% to 25% of patients with acute lymphoblastic leukemia (ALL). Unlike chronic myelogenous leukemia (CML), where the molecular detection of the Ph1 chromosome is relatively straightforward using conventional Southern hybridization analysis, the detection of the Ph1 chromosome in ALL is complicated by the existence of several molecular subtypes, and the fact that translocation breakpoints are dispersed over a large genomic area. To circumvent these difficulties, we investigated pulsed-field gel electrophoresis (PFGE) to determine if this method could be used directly on clinical samples to detect the Ph1 chromosome in ALL. We report that, in a study of seven patients with Ph1-positive ALL, we could easily detect the Ph1 using only a single PFGE analysis, regardless of the Ph1 subtype, and we could confirm that the translocations occur either within or very near the BCR gene in all seven. We conclude that PFGE is a useful technique for the detection of the Ph1 in ALL, which ultimately may find wide applicability in the detection of other chromosomal abnormalities in other malignancies.