gebhart/patrepeval huggingface dataset:
Basilar invagination in osteogenesis imperfecta and related osteochondrodysplasias: medical and surgical management (1997)

Osteogenesis imperfecta (OI) is a heritable disorder of bone development caused by defective collagen synthesis. Basilar invagination is an uncommon but devastating complication of this disease. The authors present a comprehensive strategy for management of craniovertebral anomalies associated with OI and related osteochondrodysplasias. Twenty-five patients with congenital osteochondrodysplasias (18 OI, four Hajdu-Cheney syndrome, and three spondyloepiphyseal dysplasia) and basilar invagination were evaluated between 1985 and 1995. The male/female ratio in this cohort was 1:1. The mean age at presentation was 11.9 years (range 13 months-20 years). Fourteen patients (56%) presented during adolescence (11-15 years of age). Symptoms and signs included headache (76%), lower cranial nerve dysfunction (68%), hyperreflexia (56%), quadriparesis (48%), ataxia (32%), nystagmus (28%), and scoliosis (20%). Four patients (16%) were asymptomatic. Seven (28%) had undergone previous posterior fossa decompression; one had also undergone ventral decompression. Imaging findings included basilar invagination (100%), ventral brainstem compression (84%), hydrocephalus (32%), hindbrain herniation (28%), and syringomyelia/syringobulbia (16%). Patients with hydrocephalus underwent ventricular shunt placement. Reducible basilar invagination (40%) was treated with posterior fossa decompression and occipitocervical fusion. Those with irreducible ventral compression (60%) underwent transoral-transpalatopharyngeal decompression followed by occipitocervical fusion. All patients improved initially. However, basilar invagination progressed radiographically in 80% (symptomatic in 24%) despite successful fusion. Prolonged external orthotic immobilization with the modified Minerva brace afforded symptomatic improvement and arrested progression of the deformity. The mean follow-up period was 5.9 years (range 1.1-10.5 years). Ventral brainstem compression in OI should be treated with ventral decompression, followed by occipitocervical fusion with contoured loop instrumentation to prevent further squamooccipital infolding. Despite fusion, however, basilar invagination tends to progress. Prolonged immobilization (particularly during adolescence) may stabilize symptoms and halt further invagination. This study represents the largest series to date addressing craniovertebral anomalies in OI and related congenital bone softening disorders.
Inhibition of degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in vivo by cysteine protease inhibitors (1991)

3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase is a key regulatory enzyme of cholesterol biosynthesis and is located in the endoplasmic reticulum (ER). A fusion protein, HMGal, consisting of the membrane domain of HMG-CoA reductase fused to Escherichia coli beta-galactosidase and expressed in Chinese hamster ovary (CHO) cells from the SV40 promoter, was previously constructed and was found to respond to regulatory signals for degradation in a similar fashion to the intact HMG-CoA reductase. Degradation of both HMG-CoA reductase and HMGal in CHO cells was enhanced by addition of mevalonate or low density lipoprotein (LDL). In this report we show that 2 cysteine protease inhibitors, N-acetyl-leucyl-leucyl-norleucinal (ALLN) and N-acetyl-leucyl-leucyl-methioninal (ALLM), completely inhibit the mevalonate- or LDL-accelerated degradation of HMG-CoA reductase and HMGal and also block the basal degradation of these enzymes. It has been shown that in vitro these protease inhibitors inhibit the activities of Ca(2+)-dependent neutral proteases as well as lysosomal proteases, including cathepsin L, cathepsin b, and cathepsin D. However, the mevalonate-accelerated degradation of HMG-CoA reductase and HMGal is not affected by lysosomotropic agents, suggesting that the site of action of these inhibitor peptides in preventing the degradation is not the cathepsins. In brefeldin A-treated cells, where protein export from the ER is blocked, ALLN is still effective in inhibiting the degradation of HMG-CoA reductase and HMGal. These results indicate the involvement of non-lysosomal Ca(2+)-dependent proteases in the basal and the accelerated degradation of HMG-CoA reductase and HMGal. Enzymatic assays in vitro and immunoblot analyses have revealed calpain- and calpastatin-like proteins in CHO cells. The activities and the amount of these proteins do not change under conditions of enhanced degradation, indicating that the levels of these proteins are not subject to mevalonate regulation.
The Kallikrein/Kinin System in Ocular Function (2011)

The kallikrein/kinin system uses two distinct serine proteases, plasma kallikrein and tissue kallikrein, to yield bradykinin and Lys-bradykinin (kallidin) from specific substrate kininogens. The kallikrein/kinin system is known to have a role in contact-activated coagulation mechanisms and in inflammatory responses, and recently has been shown to contribute to homeostatic and protective mechanisms in the cardiovascular and renal systems. This article reviews current knowledge of the ocular kallikrein/kinin system within the context of proposed roles for this system in other important organs and tissues. All components of the kallikrein/kinin system are present in the eye and are positioned to participate in key ocular functions. Plasma kallikrein binds to vascular endothelium and generates bradykinin, which may contribute to regulation of ocular blood flow, and, in excess, has been implicated in the pathogenesis of retinal edema in patients with proliferative diabetic retinopathy. Tissue kallikrein is expressed in retina, ciliary muscle, and trabecular meshwork cells and could be a significant factor in the protective mechanism of ischemic preconditioning, and in the modulation of aqueous dynamics. Improved understanding of the role of plasma and tissue kallikreins and kinins in such processes has the potential to identify significant new targets for the therapy of ocular dysfunction.
Estrogen suppression as a pharmacotherapeutic strategy in the medical treatment of benign prostatic hyperplasia: evidence for its efficacy from studies with mepartricin. (1998)

Estrogen suppression has been introduced as a pharmacotherapeutic strategy in the medical treatment of benign prostatic hyperplasia. Recent negative results obtained in placebo-controlled trials with the aromatase inhibitor atamestane raised doubts about the efficacy of estrogen reduction. However, inhibition of aromatase not only reduces estrogens but also increases androgens which promote prostatic growth. In order to reevaluate the therapeutic efficacy of estrogen suppression, we summarize clinical trials investigating the therapeutic effects of mepartricin in the treatment of uncomplicated benign prostatic hyperplasia. Mepartricin has been reported to lower the levels of circulating estrogens without causing changes in other hormones such as androgens. By applying stringent inclusion criteria, 23 studies (including 7 placebo-controlled trials, 3 post-marketing surveillance studies, and 13 open trials) published between 1982 and 1996 were selected to be included in this report. In 79.9% of 4635 patients treated with mepartricin, its therapeutic effect was rated "good" or "excellent". In 6 out of 7 placebo-controlled trials, the therapeutic efficacy of mepartricin was significantly superior to that of placebo. Comparison of these data with results obtained with alpha 1-adrenoceptor antagonists or with the 5 alpha-reductase inhibitor finasteride indicates that mepartricin is as efficient as these widely accepted medical treatments for benign prostatic hyperplasia. Since mepartricin acts selectively upon estrogens, the present results show that estrogen suppression may be considered an efficient pharmacotherapeutic strategy in the medical treatment of uncomplicated benign prostatic hyperplasia.
Enhanced expression of a new class of liver-enriched b-Zip transcription factors, hepatocarcinogenesis-related transcription factor, in hepatocellular carcinomas of rats and humans. (1998)

Rat hepatocarcinogenesis-related transcription factor (HTF) was earlier identified as a b-Zip transcription factor in chemically induced rat hepatocellular carcinoma (HCC) by cDNA subtraction, and its structure was found to be different from that of the conventional b-Zip proteins. We investigated htf gene expression in rat tissues by Northern analysis and found that HTF expression was ubiquitous but was enriched in the liver. HTF expression increased concomitantly with HCC development in rat liver, and the HTF-containing DNA-binding factor also increased. Stimulated HTF gene expression also was observed in rat regenerating livers. From the results of various assays, X-box-binding protein 1/Tax-response element binding factor 5 was suggested to be a human homologue of rat HTF. In humans, HTF gene expression was also abundant in the liver and was revealed to be specifically stimulated in HCCs, but not in other types of cancers. To our knowledge, HTF is the first example of a liver-enriched transcription factor that exhibits HCC-associated gene expression. Injection of anti-HTF antibody decreased the growth rate of cultured HCC cells. Consequently, HTF is thought to participate in hepatocyte growth as well as in hepatocarcinogenesis.
MICROSCOPIC CHARACTERIZATION OF OIL SANDS PROCESSING EMULSIONS (1989)

ABSTRACT Microscopic characterization of oil sands emulsions can be important in the prediction of processing characteristics and process yields in the extraction of oil from oil sands. The size distribution of the emulsion can determine how efficiently the oil can be separated from the water and by what means: mechanically or chemically. In addition, it is possible to characterize the nature of the dispersed phase by using fluorescence behaviour under an optical microscope or via x-ray analysis with a scanning electron microscope. In certain cases it is also possible to characterize the interface between the dispersed and the continuous phases. This paper presents results from our laboratory using microscopic techniques and illustrates their utility, not only for determining the morphology of these economically important emulsions, but also to characterize the composition of the interface itself.
A modified posicast method of control with applications to higher-order systems (1960)

The theory of Posicast control,1‾ <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3 by using a delayed step or steps, permits deadbeat step response from a very lightly damped system. The original development deals primarily with second-order systems, proposes a delay line technique for application of the second step, notes that use of this technique leaves the basic system underdamped, then proposes use of the delay line in a feedback path to damp load disturbances, and finally proposes the use of a tapped delay line for higher-order systems.</sub>
ATM binds to β-adaptin in cytoplasmic vesicles (1998)

Inherited mutations in the ATM gene lead to a complex clinical phenotype characterized by neuronal degeneration, oculocutaneous telangiectasias, immune dysfunction, and cancer predisposition. Using the yeast two-hybrid system, we demonstrate that ataxia telangiectasia mutated (ATM) binds to beta-adaptin, one of the components of the AP-2 adaptor complex, which is involved in clathrin-mediated endocytosis of receptors. The interaction between ATM and beta-adaptin was confirmed in vitro, and coimmunoprecipitation and colocalization studies show that the proteins also associate in vivo. ATM also interacts in vitro with beta-NAP, a neuronal-specific beta-adaptin homolog that was identified as an autoantigen in a patient with cerebellar degeneration. Our data describing the association of ATM with beta-adaptin in vesicles indicate that ATM may play a role in intracellular vesicle and/or protein transport mechanisms.
Fate of the ACL-injured Patient (1994)

We followed 292 patients who had sustained an acute traumatic hemarthrosis for a mean of 64 months. The KT-1000 arthrometer measurements within 90 days of injury revealed the injured knee was stable in 56 patients and unstable in 236. Forty-five unstable patients had an ACL reconstruction within 90 days of injury. Surgical procedures performed > 90 days after injury included ligament reconstruction in 46 patients. Factors that correlated with patients who had late surgery for a meniscal tear or an ACL reconstruction (P < 0.05) were preinjury hours of sports participation, arthrometer measurements, and patient age. Follow-up data are presented for the patients divided into four groups: I, early stable, no reconstruction; II, early unstable, no reconstruction; III, early reconstruction; and IV, late reconstruction. No patient changed occupation because of the knee injury. Hours per year of sports participation and levels of sports participation decreased in all groups. Joint arthrosis was documented by radiograph and bone scan. Joint surface injury abnormalities observed at surgery and meniscal surgery showed greater abnormalities by radiograph and bone scan scores (P < 0.05). Reconstructed patients had a higher level of arthrosis by radiograph and bone scan.
An adaptive striping architecture for flash memory storage systems of embedded systems (2003)

Flash memory is now a critical component in building embedded or portable devices because of its nonvolatile, shock-resistant, and power-economic nature. With the very different characteristics of flash memory, mechanisms proposed for many block-oriented storage media cannot be directly applied to flash memory. Distinct from the past work, we propose an adaptive striping architecture to significantly boost the system performance. The capability of the proposed mechanisms and architecture is demonstrated over realistic prototypes and workloads.
Glucagon Produced by Recombinant DNA Technology: Repeated Dose Toxicity Studies, Intravenous Administration to CD Rats and Beagle Dogs for Four Weeks (1993)

The toxicity of glucagon produced by recombinant DNA technology (Glucagon (ge)) was studied by daily intravenous administration to rats and dogs for 4 weeks. Pancreatic glucagon of bovine or porcine origin (Glucagon Novo) was used as a reference control in the dogs. Glucagon (ge) has the same sequence of the 29 amino acids as pancreatic glucagon of humans, cows, pigs, rats and dogs. The dosages were 0 (control), 0.2, 1.0 and 5.0 mg Glucagon (ge)/kg/day in the rats, and 0 (control), 1.0 and 5.0 mg Glucagon (ge) and 5.0 mg Glucagon (Novo)/kg/day in the dogs. The studies complied with current EEC, US and Japanese guidelines for 4 week toxicity studies of drugs. All dose levels were well tolerated. The plasma glucose and cardiovascular responses to dosing were monitored in the dogs and found to be in agreement with well-known effects of pancreatic glucagon. The most consistent finding in both species was an increase in liver weight. This change was without concomitant pathological deviations in the other parameters examined. There were no differences in the reaction of dogs following treatment with Glucagon (ge) or Glucagon (Novo). A dose of 1 mg Glucagon (ge)/kg/day was regarded as a clear no-toxic-effect-level in both species.
α-1 Antitrypsin Promotes Semimature, IL-10–Producing and Readily Migrating Tolerogenic Dendritic Cells (2012)

Tolerogenic IL-10-positive CCR7-positive dendritic cells (DC) promote T regulatory (Treg) cell differentiation upon CCR7-dependent migration to draining lymph nodes (DLN). Indeed, in human DC deficiencies, Treg levels are low. α-1 antitrypsin (AAT) has been shown to reduce inflammatory markers, promote a semimature LPS-induced DC phenotype, facilitate Treg expansion, and protect pancreatic islets from alloimmune and autoimmune responses in mice. However, the mechanism behind these activities of AAT is poorly understood. In this study, we examine interactions among DC, CD4(+) T cells, and AAT in vitro and in vivo. IL-1β/IFN-γ-mediated DC maturation and effect on Treg development were examined using OT-II cells and human AAT (0.5 mg/ml). CCL19/21-dependent migration of isolated DC and resident islet DC was assessed, and CCR7 surface levels were examined. Migration toward DLN was evaluated by FITC skin painting, transgenic GFP skin tissue grafting, and footpad DC injection. AAT-treated stimulated DC displayed reduced MHC class II, CD40, CD86, and IL-6, but produced more IL-10 and maintained inducible CCR7. Upon exposure of CD4(+) T cells to OVA-loaded AAT-treated DC, 2.7-fold more Foxp3(+) Treg cells were obtained. AAT-treated cells displayed enhanced chemokine-dependent migration and low surface CD40. Under AAT treatment (60 mg/kg), DLN contained twice more fluorescence after FITC skin painting and twice more donor DC after footpad injection, whereas migrating DC expressed less CD40, MHC class II, and CD86. Intracellular DC IL-10 was 2-fold higher in the AAT group. Taken together, these results suggest that inducible functional CCR7 is maintained during AAT-mediated anti-inflammatory conditions. Further studies are required to elucidate the mechanism behind the favorable tolerogenic activities of AAT.
Hair Follicle–Derived Blood Vessels Vascularize Tumors in Skin and Are Inhibited by Doxorubicin (2005)

We have recently shown that the neural-stem cell marker nestin is expressed in hair follicle stem cells and the blood vessel network interconnecting hair follicles in the skin of transgenic mice with nestin regulatory element-driven green fluorescent protein (ND-GFP). The hair follicles were shown to give rise to the nestin-expressing blood vessels in the skin. In the present study, we visualized tumor angiogenesis by dual-color fluorescence imaging in ND-GFP transgenic mice after transplantation of the murine melanoma cell line B16F10 expressing red fluorescent protein. ND-GFP was highly expressed in proliferating endothelial cells and nascent blood vessels in the growing tumor. Results of immunohistochemical staining showed that the blood vessel-specific antigen CD31 was expressed in ND-GFP-expressing nascent blood vessels. ND-GFP expression was diminished in the vessels with increased blood flow. Progressive angiogenesis during tumor growth was readily visualized during tumor growth by GFP expression. Doxorubicin inhibited the nascent tumor angiogenesis as well as tumor growth in the ND-GFP mice transplanted with B16F10-RFP. This model is useful for direct visualization of tumor angiogenesis and evaluation of angiogenic inhibitors.
Microfluidic diffusive filter for apheresis (leukapheresis) (2005)

Apheresis is a procedure used to fractionate whole blood into its individual components. Following fractionation, the desired component is isolated and the remaining blood in many cases is returned to the donor. Leukapheresis is one type of apheresis where leukocytes (white blood cells) are selectively removed. This procedure is commonly used for blood transfusions to remove donor leukocytes from being transferred to the recipient. Apheresis also has several therapeutic applications. In this manuscript we discuss the design, fabrication and testing of a continuous flow diffusive filter, fabricated using simple soft lithographic techniques for depletion of leukocytes. This device employs micro sieves that exploit the size and shape difference between the different cell types to obtain depletion of leukocytes from whole blood. Currently, conventional apheresis methods like centrifugation or fiber mesh filtration are commonly used. A theoretical model was developed to determine the optimal shape of the diffuser to ensure that the volumetric flow through individual sieve elements is equal. This device was designed to serve as a passive device that does not require any external manipulation. Results show that for the given device design, isolation of approximately 50% of the inlet erythrocytes (red blood cells), along with depletion of >97% of the inlet leukocytes is possible at a flow rate of 5 microl min(-1). Simple modifications to the geometry and dimensions of the sieves can be made to obtain isolation of plasma.
HBV-ISS (Dynavax). (2006)

Dynavax is developing HBV-ISS (Heplisav), a vaccine based on hepatitis B virus (HB V) antigens and Dynavax' s immunostimulatory DNA sequence (ISS) ISS-1018, an adjuvant that acts as a TLR-9 agonist, for the potential prevention and treatment of HBV infection.
Roles of lipid rafts in integrin‐dependent adhesion and gp130 signalling pathway in mouse embryonic neural precursor cells (2004)

Neuronal and glial cells organizing the central nervous system are generated from common neural precursor cells present in the neuroepithelium during development. We tried to clarify functions of a cell surface microdomain, lipid raft, in neuroepithelial cells (NECs). NECs are suggested to adhere to fibronectin substratum dependently on integrin molecules. We found that beta1 integrin, a component of fibronectin receptors, was distributed in lipid rafts. Methyl-beta-cyclodextrin (MBCD), an inhibitor of lipid raft formation, inhibited the integrin-fibronectin interaction-dependent adhesion of NECs. However, inhibition of synthesis of glycosphingolipids (GSL), components of lipid rafts, did not affect NEC adhesion. Leukaemia inhibitory factor (LIF), an interleukin 6 type cytokine, induces astrocyte differentiation of NECs via activation of a transcription factor STAT3. We detected gp130, JAK1 and Ras but not STAT3 and ERK2 molecules in lipid rafts of NECs. Disruption of lipid rafts by MBCD inhibited LIF-induced ERK activation but not STAT3 activation. It is thus suggested that LIF-downstream molecules have differential lipid raft-dependency in terms of activation upon LIF-stimulation. In this study, we found functions of lipid rafts in cell adhesion and signal transduction in NECs. This is the first report that characterized functions of lipid rafts in embryonic neural precursor cells.
The spectrum of JAK2-positive myeloproliferative neoplasms (2012)

Abstract The discovery of the JAK2V617F mutation triggered an unexpected flowering of basic and clinical studies in the field of myeloproliferative neoplasms (MPNs), resulting after just a few years in an exceptional amount of new information. One important consequence of those new findings was the modification of the World Health Organization classification and diagnostic algorithms for these diseases, which is still based on the original concept developed by William Dameshek in 1951 and keeps distinct entities under the umbrella of classical Philadelphia-negative MPNs. These MPNs are essential thrombocythemia, polycythemia vera, and primary myelofibrosis. Could a new molecular classification be a better tool to manage MPN patients? Several studies have shown that essential thrombocythemia and primary myelofibrosis can be divided into distinct subtypes based on the presence of the JAK2V617F mutation. Can we now define JAK2-positive diseases to depict a distinct entity from JAK2-negative MPNs? This chapter reviews the significance of JAK2 mutation positivity in the diagnosis, prognosis, and therapy of MPNs.