gebhart/patrepeval huggingface dataset:
An Investigation into the Suitability of Amidated Pectin Hydrogel Beads as a Delivery Matrix for Chloroquine (1998)

The aim of the present study was to delay the release of chloroquine to distal parts of the gastrointestinal tract by using a multiparticulate hydrogel formulation. Amidated pectin chloroquine beads (PC) with varying pectin-to-chloroquine ratios (PC) w/w loadings of 4:1, 2:1, and 1:1 in the dried beads were prepared by the gelation of drug-loaded pectin solutions in the presence of calcium. In vitro release studies of chloroquine from pectin-chloroquine hydrogel beads and chloroquine diphosphate powder were carried out in simulated gastric and intestinal fluids. The total release of the entrapped chloroquine from the hydrogel beads was achieved between 4 and 7 h in simulated intestinal fluid, but total release was not achieved in simulated gastric fluid. However, total release from chloroquine diphosphate powder was achieved by 1.5 and 2 h in gastric and intestinal fluids, respectively. The plasma pharmacokinetics of chloroquine from pectin hydrogel beads and chloroquine diphosphate solution following single or repeated dosing were compared in male Sprague-Dawley rats over a period of 60 h. Oral administration of the hyrogel beads to rats produced maximum plasma concentrations by 7 h, but highest plasma concentrations following chloroquine solution administration were observed by 2 h. The dissolution data and appearance of significant plasma concentrations of chloroquine 2 to 4 h after oral administration suggests release in duodenum, jejunum, or ileum.
Neonatal mycobacterial specific cytotoxic T‐lymphocyte and cytokine profiles in response to distinct BCG vaccination strategies (2002)

This study evaluated whether different bacillus Calmette-Guérin (BCG) strains, routes of administration, vaccination age and percutaneous tools influenced immune responses to BCG vaccination in infants. Proliferative responses, cytokine production and cell-mediated cytotoxicity obtained in post-vaccinated children were compared to baseline cord bloods and unvaccinated 10-week-old infants. BCG vaccination generally induced strong lymphoproliferative and T helper type 1 (Th1)-type cytokine responses. There was a trend for greater responsiveness following the intradermal route of vaccination, with Japanese-172 strain and with delaying vaccination until 10 weeks. Cord mononuclear cells differentially stimulated the Th2-type cytokines interleukin-5 (IL-5) and IL-10 selectively in response to BCG, as compared to H37Rv or purified protein derivative stimulation. We document for the first time the generation of mycobacterium-specific cytotoxic T lymphocytes in neonates, following BCG vaccination. Cytotoxic activity correlated with the ratio of interferon-gamma to IL-5, aside from a single instance where use of the Biovac tool resulted in a striking dissociation selectively against H37Rv targets. These data have implications for correlates of protective immunity in design of vaccine studies.
Detection of Human Bocavirus in Japanese Children with Lower Respiratory Tract Infections (2006)

Human bocavirus (HBoV), a newly cloned human virus of the genus Bocavirus, was detected by PCR from nasopharyngeal swab samples (8 of 318; 5.7%) collected from children with lower respiratory tract infections. HBoV may be one of the causative agents of lower respiratory tract infections in young children.
Thrombospondin 1 synthesis and function in wound repair. (1996)

Thrombospondin 1 (TSP1) is a multifunctional extracellular matrix molecule that belongs to a family of homologous glycoproteins. TSP1 can be produced by many cell types that are involved in wound repair, including keratinocytes, fibroblasts, endothelial cells, and macrophages. To investigate the kinetics of TSP1 synthesis in wounds, mRNA from murine full thickness excisional dermal wounds was analyzed. TSP1 mRNA was undetectable in normal skin but was present in early wounds. After day 1, TSP1 mRNA levels within wounds slowly decreased, returning to undectable day 10. In situ hybridization revealed that the primary source of the TSP1 mRNA within wounds was macrophage-like cells in the inflammatory infiltrate. To explore the function of TSP1 production in sites of injury, wounds were treated with antisense TSP1 oligomers. Antisense-treated wounds contained 55 to 66% less TSP1-positive macrophages than control and exhibited a marked delay in repair. This delay included a decreased rate of re-epithelialization as well as a delay in dermal reorganization. The results suggest that TSP1 production by macrophages facilitates the repair process and provide evidence that TSP1 production is an important component of optimal wound healing.
Mechanism-based isocoumarin inhibitors for trypsin and blood coagulation serine proteases: new anticoagulants (1988)

Trypsin, porcine pancreatic kallikrein, and several blood coagulation enzymes, including bovine thrombin, bovine factor Xa, human factor Xa, human plasma factor XIa, human plasma factor XIIa, and human plasma kallikrein, were inactivated by a number of substituted isocoumarins containing basic functional groups (aminoalkoxy, guanidino, and isothiureidoalkoxy). 3-Alkoxy-4-chloro-7-guanidinoisocoumarins were found to be the most potent inhibitors for the coagulation enzymes tested with kobsd/[I] values in the range of 10(3)-10(5) M-1 s-1. 4-Chloro-3-isothiureidoalkoxyisocoumarins show high inhibitory potency toward porcine pancreatic kallikrein, human plasma kallikrein, human factor XIa, human factor XIIa, and trypsin with kobsd/[I] values of the order of 10(4)-10(5) M-1 s-1. The inhibition of these serine proteases by the substituted isocoumarins are time dependent, and the inactivation of trypsin by 3-alkoxy-4-chloro-7-guanidinoisocoumarins and 7-amino-4-chloro-3-(3-isothiureidopropoxy)isocoumarin occured concurrently with the loss of the isocoumarin absorbance. The complex formed from inactivation of trypsin by these two types of inhibitors was very stable and regained less than 4% activity in 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid buffer (pH 7.5) after 1 day at 25 degrees C and regained 8-45% activity upon addition of buffered 0.29 M hydroxylamine. Trypsin inactivated by other inhibitors regained full activity upon standing or addition of hydroxylamine. Thrombin inactivated by 3-alkoxy-4-chloro-7-guanidinoisocoumarins was also quite stable and only regained 9-15% activity under similar conditions. These results are consistent with a proposed mechanism, where serine proteases inactivated by aminoalkoxyisocoumarins or isothiureidoalkoxyisocoumarins form acyl enzymes that will deacylate upon standing or addition of hydroxylamine. However, the acyl enzymes formed from 3-alkoxy-4-chloro-7-guanidinoisocoumarins or 7-amino-4-chloro-3-(3-isothiureidopropoxy)-isocoumarin will decompose further, probably through a quinone imine methide, to give an irreversibly inactivated enzyme by reaction with an active-site nucleophile such as His-57. The quinone imine methide intermediate may also react with a solvent nucleophile to give an acyl enzyme that can be reactivated by hydroxylamine. The inhibitors 4-chloro-7-guanidino-3-methoxyisocoumarin and 4-chloro-3-ethoxy-7-guanidinoisocoumarin have been tested as anticoagulants in human plasma and were effective at prolonging the prothrombin time. However, they are unstable in plasma (t1/2 = 4-8 min), and their in vivo utility may be limited.
Phenazines and Other Redox-Active Antibiotics Promote Microbial Mineral Reduction (2004)

Natural products with important therapeutic properties are known to be produced by a variety of soil bacteria, yet the ecological function of these compounds is not well understood. Here we show that phenazines and other redox-active antibiotics can promote microbial mineral reduction. Pseudomonas chlororaphis PCL1391, a root isolate that produces phenazine-1-carboxamide (PCN), is able to reductively dissolve poorly crystalline iron and manganese oxides, whereas a strain carrying a mutation in one of the phenazine-biosynthetic genes (phzB) is not; the addition of purified PCN restores this ability to the mutant strain. The small amount of PCN produced relative to the large amount of ferric iron reduced in cultures of P. chlororaphis implies that PCN is recycled multiple times; moreover, poorly crystalline iron (hydr)oxide can be reduced abiotically by reduced PCN. This ability suggests that PCN functions as an electron shuttle rather than an iron chelator, a finding that is consistent with the observation that dissolved ferric iron is undetectable in culture fluids. Multiple phenazines and the glycopeptidic antibiotic bleomycin can also stimulate mineral reduction by the dissimilatory iron-reducing bacterium Shewanella oneidensis MR1. Because diverse bacterial strains that cannot grow on iron can reduce phenazines, and because thermodynamic calculations suggest that phenazines have lower redox potentials than those of poorly crystalline iron (hydr)oxides in a range of relevant environmental pH (5 to 9), we suggest that natural products like phenazines may promote microbial mineral reduction in the environment.
Hypothesis: Multiple Sclerosis is a Type I Interferon Deficiency Syndrome (1998)

Multiple sclerosis (MS), a chronic demyelinating disease of the central nervous system (CNS), is in part an immune mediated disease (1). MS is clinically associated with periods of disability (relapse) alternating with periods of recovery (remission) but often leading to progressive neurological disability (2). White matter lesions in the CNS are associated with mononuclear infiltrates that consist primarily of T cells and macrophages and resemble the lesion produced by T-lymphocyte delayed type hypersensitivity (DTH) (2–3). Alternatively, T-cell infiltration may not be the "initial hit" but T cells may be recruited secondarily by the release of chemokines from activated macrophages (4). Activated immune cells in the CNS lead to inflammation and eventually demyelination. MS has been associated with abnormalities of immunoregulation (5).We propose a unifying hypothesis of the etiopathogenesis of MS that mirrors the relapsing-remitting character of clinical MS and defines MS as a type I interferon (IFN) immunodeficiency syndrome. At the core of our unifying theory is the interaction between the two major components of the immune system, the older innate and the newer acquired immune systems. Foreign nucleic acids, cells, and bacteria cause type I IFN secretion by the innate immune system and act as the initial nonspecific antiviral, antibacterial, and antiproliferative defense system. Type I IFN secretion activates antigen-presenting cells, allowing the transition into antigen-specific humoral and cell-mediated immunity. However the products of the innate immune system, type I IFNs, can also function as immunomodulators to balance the effects of the acquired immune system. We hypothesize that under normal circumstances there is a dynamic interaction between the innate immune system that initially generates antiforeign and secondarily immunomodulating cytokines, including IFN-α/β (type I IFNs), and the acquired immune system that generates pro-inflammatory IFN-γ (type II IFN), resulting in a physiological downmodulation of the total immune response. In MS and possibly in other autoimmune diseases, there may be a deficiency of immunomodulation of the innate immune system.
Clinical and Virological Features of Dengue in Vietnamese Infants (2010)

Collectively, these results provide a systematic description of the clinical features of dengue in infants and highlight the value of NS1 detection for diagnosis.
Type XII and XIV collagens mediate interactions between banded collagen fibers in vitro and may modulate extracellular matrix deformability. (1994)

Type XII and XIV collagens are very large molecules containing three extended globular domains derived from the amino terminus of each alpha chain and an interrupted triple helix. Both collagens are genetically and immunologically unique and have distinct distributions in many tissues. These collagens localize near the surface of banded collagen fibrils. The function of the molecules is unknown. We have prepared a mixture of native type XII and XIV collagens that is free of contaminating proteins by electrophoretic criteria. In addition, we have purified the collagenase-resistant globular domains of type XII or XIV collagens (XII-NC-3 or XIV-NC-3). In this study, we have investigated the effect of intact type XII and XIV and XII-NC-3 or XIV-NC-3 on the interactions between fibroblasts and type I collagen fibrils. We find that both type XII and XIV collagens promote collagen gel contraction mediated by fibroblasts, even in the absence of serum. The activity is present in the NC-3 domains. The effect is dose-dependent and is inhibited by denaturation. The effect of type XII NC-3 is inhibited by the addition of anti-XII antiserum. To elucidate the mechanism underlying this phenomenon, we examined the effect of XII-NC-3 or XIV-NC-3 on deformability of collagen gels by centrifugal force. XII-NC-3 or XIV-NC-3 markedly promotes gel compression after centrifugation. The effect is also inhibited by denaturation, and the activity of type XII-NC3 is inhibited by the addition of anti-XII antiserum. The results indicate that the effect of XII-NC-3 or XIV-NC-3 on collagen gel contraction by fibroblasts is not due to activation of cellular events but rather results from the increase in mobility of hydrated collagen fibrils within the gel. These studies suggest that collagen types XII and XIV may modulate the biomechanical properties of tissues.
Long‐term transduction of miniature pig parotid glands using serotype 2 adeno‐associated viral vectors (2009)

AAV2 vectors mediate extended gene transfer to miniature pig parotid glands and should be useful for testing pre-clinical gene therapy strategies aiming to correct salivary gland radiation damage.
Programmed death-1 expression is associated with the disease status in hepatitis B virus infection (2008)

瞄准：定义规划 death-1/programmed death-ligand (PD-1/PD-L ) 的潜在的角色在不同肝炎 B (HBV ) 感染的小径疾病地位；我们与长期的肝炎 B (CHB ) 和肝炎 B (AEHB ) 感染的尖锐恶化在病人的外部血在抗原 specific CD8+ T 房间上检验了 PD-1 的表示。方法：CD8+ T 淋巴细胞和在病人和健康控制(HC ) 的 HBV 特定的 CD8+ T 淋巴细胞的数字上的 PD-1 水平被与建筑群与流动血细胞计数相结合的 pentameric 肽人白血球 antigen2 (HLA2 ) 染色分析。实时量的聚合酶链反应(PCR ) 被用来测量浆液 HBV-DNA 层次。结果：在 CHB 病人的全部的 CD8+ T 房间上的 PD-1 表示的水平(13.86%+/-3.38%) 在 AEHB 病人比那显著地高(6.80%+/-2.19% ， P 0.05 ) 。结论：我们的结果证实在外部血的 HBV 特定的 CD8+T 房间反应比在有坚持的病毒的感染的长期的肝炎 B 在有 AEHB 的病人是更强烈的以前的报告。而且，在 PD-1 的水平和病毒 specific CD8+ T 房间反应的紧张之间有否定关联。
Detection of trisomy 12 in chronic lymphocytic leukemia by fluorescence in situ hybridization to interphase cells: a simple and sensitive method (1992)

Trisomy 12 is the most common cytogenetic abnormality in chronic lymphocytic leukemia (CLL), and a number of studies have suggested that it may be an adverse prognostic indicator. We have evaluated the usefulness of fluorescence in situ hybridization with a chromosome 12-specific probe as a simple means for detecting trisomy 12 in interphase cells. Forty cases of B-cell CLL previously studied with conventional cytogenetic techniques were analyzed with a biotinylated probe to the centromeric region of chromosome 12. Thirty of these retrospective cases could be reevaluated with in situ hybridization. Our analysis showed three hybridization signals (ie, trisomy 12) in interphase cells from seven of seven cases found previously to have trisomy 12. Trisomy 12 was also detected in five additional cases: in one case thought to have a normal karyotype, in two cases that had been inadequate for routine cytogenetic analysis, and in two cases that had been found to have an abnormal karyotype without trisomy 12. In a prospective series of 20 newly accrued CLL cases, all cases were analyzed successfully by in situ hybridization and six (30%) showed trisomy 12. We were able to perform the analysis on routinely prepared and previously Wright-stained peripheral blood smears. We conclude that fluorescence in situ hybridization is a simple means for the detection of trisomy 12 in CLL. The technique is more sensitive than conventional cytogenetic analysis and would be a useful tool in clinical studies.
Representative cDNA libraries from few plant cells (1994)

A reverse transcriptase/polymerase chain reaction (RT/PCR) method for the construction of representative cDNA libraries originating from few isolated cells is described. Poly(A)+ RNA was extracted from an average of 100 maize cells and reverse transcribed into sscDNA. The sscDNA was dG-tailed at its 3' end and amplified during a two-step PCR reaction. The generated PCR products were analysed and the majority < or = 2 kbp were full-size cDNAs. A fraction of the amplified cDNA from 128 isolated maize egg cells was cloned into the lambda Uni-ZAP XR vector and a primary library of 6.8 x 10(6) p.f.u. was obtained. The average insert size is 860 bp. It was further determined, that 0.31% of the clones hybridized to a cytosolic GAPDH probe. It is thought that, with this method, the first cDNA library of egg cells in higher plants was generated.
Tensile Strengths of Various Suture Techniques (1997)

The tensile strengths of various suture techniques were studied in vitro using rabbit Achilles' and flexor digitorum longus tendons. Two new suture methods, a Double and Triple (modified) Kessler, were compared with the Savage, Indiana and modified Kessler techniques. All were core sutures without epitendinous sutures. All suture techniques were found to be significantly different for 2 mm of gap formation. The study found the Savage technique strongest, followed by the Triple Kessler, the Double Kessler, and finally the Indiana. The Double Kessler was almost twice as strong as the modified Kessler. This study also compared two four-stranded techniques (the Indiana and Double Kessler) and found the Double Kessler stronger. The Double Kessler is a simple yet strong suture and may be useful for flexor tendon repairs.
Breast Milk Oligosaccharides: Structure-Function Relationships in the Neonate (2014)

In addition to providing complete postnatal nutrition, breast milk is a complex biofluid that delivers bioactive components for the growth and development of the intestinal and immune systems. Lactation is a unique opportunity to understand the role of diet in shaping the intestinal environment including the infant microbiome. Of considerable interest is the diversity and abundance of milk glycans that are energetically costly for the mammary gland to produce yet indigestible by infants. Milk glycans comprise free oligosaccharides, glycoproteins, glycopeptides, and glycolipids. Emerging technological advances are enabling more comprehensive, sensitive, and rapid analyses of these different classes of milk glycans. Understanding the impact of inter- and intraindividual glycan diversity on function is an important step toward interventions aimed at improving health and preventing disease. This review discusses the state of technology for glycan analysis and how specific structure-function knowledge is enhancing our understanding of early nutrition in the neonate.
Asymmetric synthesis of 1,3-dioxolane-pyrimidine nucleosides and their anti-HIV activity. (1992)

In order to study the structure-activity relationships of dioxolane nucleosides as potential anti-HIV agents, various enantiomerically pure dioxolane-pyrimidine nucleosides have been synthesized and evaluated against HIV-1 in human peripheral blood mononuclear cells. The enantiomerically pure key intermediate 8 has been synthesized in nine steps from 1,6-anhydro-D-mannose (1), which was condensed with 5-substituted pyrimidines to obtain various dioxolane-pyrimidine nucleosides. Upon evaluation of these compounds, cytosine derivative 19 was found to exhibit the most potent anti-HIV agent although it is the most toxic. The order of anti-HIV potency was as follows: cytosine (beta-isomer) greater than thymine greater than cytosine (alpha-isomer) greater than 5-chlorouracil greater than 5-bromouracil greater than 5-fluorouracil derivatives. Uracil, 5-methylcytosine, and 5-iodouracil derivatives were found to be inactive. Interestingly, alpha-isomer 20 showed good anti-HIV activity without cytotoxicity. As expected, other alpha-isomers did not exhibit any significant antiviral activity. (-)-Dioxolane-T was 5-fold less effective against AZT-resistant virus than AZT-sensitive virus.
Identification of a Precursor of β-Methyl-γ-octalactone in the Wood of Sessile Oak (Quercus petraea(Matt.) Liebl.) (2000)

The 6'-O-gallate derivative of (3S, 4S)-4-beta-D-glucopyranosyloxy-3-methyloctanoic acid was isolated for the first time from the wood of Sessile oak (Quercus petraea (Matt.) Liebl.) and shown to be a precursor of cis-beta-methyl-gamma-octalactone. The structure of this precursor was determined by HRFAB-MS, NMR, LCMS, and chiral analysis of the liberated (3S,4S)-beta-methyl-gamma-octalactone on a chiral fused silica capillary column. Optical rotation was shown to be identical to that of the same compound previously isolated from the wood of Platycarya strobilacea Sieb. et Zucc. by Tanaka and Kouno in 1996. Moreover, the 6'-O-gallate derivative of a threo-4-beta-D-glucopyranosyloxy-3-methyloctanoic acid was tentatively identified as a minor precursor of trans-beta-methyl-gamma-octalactone in the same wood of Sessile oak.
Immunomodulatory Activity of Synthetic Triterpenoids: Inhibition of Lymphocyte Proliferation, Cell-Mediated Cytotoxicity, and Cytokine Gene Expression Through Suppression of NF-κB (2008)

Synthetic oleanane triterpenoids (CDDO, CDDO-Im and CDDO-Me) are potent anti-inflammatory agents, but have not been investigated for effects on T cell-mediated immune responses. Here we demonstrate that CDDOs have profound immunosuppressive effects on T cell proliferation, development of IL-2 activated LAK cells and cytotoxic T lymphocytes (CTLs), and expression of cytokines at concentrations of 1.25 microM to 0.078 microM. Treatment with CDDO-Me also inhibited the generation of allo-reactive T cell responses in vivo. The suppression of these cell-mediated immune responses by CDDO-Me was associated with the inhibition of NF-kappaB transcription factor.
Outpatient intravenous ketamine for the treatment of complex regional pain syndrome: A double-blind placebo controlled study (2009)

Complex regional pain syndrome (CRPS) is a severe chronic pain condition that most often develops following trauma. The pathophysiology of CRPS is not known but both clinical and experimental evidence demonstrate the important of the NMDA receptor and glial activation in its induction and maintenance. Ketamine is the most potent clinically available safe NMDA antagonist that has a well established role in the treatment of acute and chronic pain. This randomized double-blind placebo controlled trial was designed to evaluate the effectiveness of intravenous ketamine in the treatment of CRPS. Before treatment, after informed consent was obtained, each subject was randomized into a ketamine or a placebo infusion group. Study subjects were evaluated for at least 2 weeks prior to treatment and for 3 months following treatment. All subjects were infused intravenously with normal saline with or without ketamine for 4h (25ml/h) daily for 10 days. The maximum ketamine infusion rate was 0.35mg/kg/h, not to exceed 25mg/h over a 4h period. Subjects in both the ketamine and placebo groups were administered clonidine and versed. This study showed that intravenous ketamine administered in an outpatient setting resulted in statistically significant (p<0.05) reductions in many pain parameters. It also showed that subjects in our placebo group demonstrated no treatment effect in any parameter. The results of this study warrant a larger randomized placebo controlled trial using higher doses of ketamine and a longer follow-up period.