gebhart/patrepeval huggingface dataset:
Phenotype, Cytotoxic, and Helper Functions of T Cells from Varicella Zoster Virus Stimulated Cultures of Human Lymphocytes (1989)

Blood mononuclear cells (MNC) were stimulated with VZV in the form of live cell-associated virus, glutaraldehyde-fixed VZV-infected fibroblasts or an extracted VZV antigen. After 7 days of culture with live virus, IL2 receptors (IL2R) were found on CD4 and CD8 cells while cultures stimulated with fixed or extracted antigen had IL2R only on CD4 cells. Clones derived by limiting dilution from these cultures were tested for specificity by cytotoxicity to autologous VZV-superinfected B lymphoblasts, and by proliferation in the presence of antigen and antigen presenting cells. The CD8+ clones were not VZV specific in tests of cytotoxicity or proliferation. 50% of the CD4+ clones with specificity for VZV also proliferated in cultures stimulated with individual VZV glycoproteins gp I, II or III. Included amongst these were clones cytotoxic for lymphoblast targets prepared with live VZV. Most of the VZV-specific T cell clones which failed to lyse targets prepared with live VZV lysed targets prepared with heat killed VZV. Target cells were susceptible to lysis after VZV antigens were no longer demonstrable on the cell surface by immunofluorescence and monoclonal antibodies to VZV glycoproteins failed to block cytotoxicity. 5 of 8 VZV-specific CD4+ clones provided antigen-specific help to B cells for IgG antibody production. The data are consistent with the view that CD4+ T cells respond to processed VZV antigen fragments, and that these fragments include epitopes present on gp I, gp II and gp III. Additionally, some the cloned progeny of VZV specific T cells were bifunctional (expressing cytotoxicity and help for B cells) in tissue culture.
Thrombomodulin Deficiency in Human Diabetic Nerve Microvasculature (2002)

Human diabetic neuropathy is multifactorial in etiology, with ischemia as a final common pathology. Although impaired vascular endothelial cell function in diabetic microvascular injury is established, the role of thrombomodulin (TM)-dependent protein C antithrombotic mechanism in the pathogenesis of neuropathy is unclear. This neuropathologic case-control study investigated whether vascular endothelial TM expression is deficient in peripheral nerve microvessels in diabetic neuropathy. Sural nerve biopsies from 7 patients with diabetic neuropathy and 10 with axonal neuropathy without vasculopathy were immunostained with anti-TM and anti-von Willebrand factor (vWF; an endothelial cell marker) antibodies. The proportion of TM-positive microvessels was expressed relative to total vWF-staining vessels, according to vessel caliber and regional distribution within the nerve. In diabetic nerves compared with reference controls, the proportion of TM-positive endoneurial microvessels was 15-fold lower (0.02 vs. 0.30 in diabetic nerves vs. controls, P < 0.004), and the proportion of small-caliber epineurial microvessels was 10-fold lower (0.04 vs. 0.43, P < 0.001). No TM expression was detected at the perineurium in diabetic or control nerves. We demonstrate a substantial reduction of vascular endothelial TM expression throughout human diabetic neuropathy. These findings suggest that an impaired native TM-dependent protein C antithrombotic mechanism may contribute to microvascular ischemia in the pathogenesis of diabetic neuropathy.
The Time Course of Glutamate in the Synaptic Cleft (1992)

The peak concentration and rate of clearance of neurotransmitter from the synaptic cleft are important determinants of synaptic function, yet the neurotransmitter concentration time course is unknown at synapses in the brain. The time course of free glutamate in the cleft was estimated by kinetic analysis of the displacement of a rapidly dissociating competitive antagonist from N-methyl-D-aspartate (NMDA) receptors during synaptic transmission. Glutamate peaked at 1.1 millimolar and decayed with a time constant of 1.2 milliseconds at cultured hippocampal synapses. This time course implies that transmitter saturates postsynaptic NMDA receptors. However, glutamate dissociates much more rapidly from alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. Thus, the time course of free glutamate predicts that dissociation contributes to the decay of the AMPA receptor-mediated postsynaptic current.
Topiramate increases cerebral GABA in healthy humans (1998)

Topiramate (TOP) is a novel anticonvulsant drug with multiple mechanisms of action used in the treatment of epilepsy. Measurements of cerebral GABA were obtained in six controls using 1H MRS at baseline and at 3 and 6 hours following the administration of 3 mg/kg of TOP. Brain GABA concentrations rose by 72% at 3 hours and by 64% at 6 hours compared with baseline (p < 0.004). This study demonstrates that TOP significantly increases human cerebral GABA concentrations in healthy individuals.
Epitope glycosylation plays a critical role for T cell recognition of type II collagen in collagen-induced arthritis (1998)

Immunization of mice with type II collagen (CII) leads to collagen-induced arthritis (CIA), a model for rheumatoid arthritis. T cell recognition of CII is believed to be a critical step in CIA development. We have analyzed the T cell determinants on CII and the TCR used for their recognition, using twenty-nine T cell hybridomas derived from C3H.Q and DBA/1 mice immunized with rat CII. All hybridomas were specific for the CII(256-270) segment. However, posttranslational modifications (hydroxylation and variable O-linked glycosylation) of the lysine at position 264 generated five T cell determinants that were specifically recognized by different T cell hybridoma subsets. TCR sequencing indicated that each of the five T cell epitopes selected its own TCR repertoire. The physiological relevance of this observation was shown by in vivo antibody-driven depletion of TCR Valpha2-positive T cells, which resulted in an inhibition of the T cell proliferative response in vitro towards the non-modified CII(256-270), but not towards the glycosylated epitope. Most hybridomas (20/29) specifically recognized CII(256-270) glycosylated with a monosaccharide (beta-D-galactopyranose). We conclude that this glycopeptide is immunodominant in CIA and that posttranslational modifications of CII create new T cell determinants that generate a diverse TCR repertoire.
Optical near-field probe action in microdisk laserwith 0.12λ resolution (1999)

Optical near-field probe action in microdisk laser with 0.12λ resolution Near-field probe action in a 1.55 µm GaInAsP/InP microdisk injection laser is demonstrated. A high spatial resolution of 190 nm was determined by using a sharp Pt-Ir needle as a target object. It was nearly 0.12 times the lasing wavelength.
Cancer dormancy. VII. A regulatory role for CD8+ T cells and IFN-gamma in establishing and maintaining the tumor-dormant state. (1999)

Dormant tumor cells resistant to ablative cancer therapy represent a significant clinical obstacle due to later relapse. Experimentally, the murine B cell lymphoma (BCL1) is used as a model of tumor dormancy in mice vaccinated with the BCL1 Ig. Here, we used this model to explore the cellular mechanisms underlying dormancy. Our previous studies have demonstrated that T cell-mediated immunity is an important component in the regulation of tumor dormancy because Id-immune T cells adoptively transferred into passively immunized SCID mice challenged with BCL1 cells significantly increased the incidence and duration of the dormant state. We have extended these observations and demonstrate that CD8+, but not CD4+, T cells are required for the maintenance of dormancy in BCL1 Ig-immunized BALB/c mice. In parallel studies, the transfer of Id-immune CD8+ cells, but not Id-immune CD4+ cells, conferred significant protection to SCID mice passively immunized with nonprotective levels of polyclonal anti-Id and then challenged with BCL1 cells. Furthermore, the ability of CD8+ T cells to induce a state of dormancy in passively immunized SCID mice was completely abrogated by treatment with neutralizing alpha-IFN-gamma mAbs in vivo. In vitro studies demonstrated that IFN-gamma alone or in combination with reagents to cross-link the surface Ig induced both cell cycle arrest and apoptosis in a BCL1 cell line. Collectively, these data demonstrate a role for CD8+ T cells via endogenous production of IFN-gamma in collaboration with humoral immunity to both induce and maintain a state of tumor dormancy.
Coping with syntactic ambiguity or how to put the block in the box on the table (1982)

Sentences are far more ambiguous than one might have thought. There may be hundreds, perhaps thousands of syntatic parse trees for certain very natural sentences of English. This fact has been a major problem confronting natural language processing because it indicates that it may require a long time to construct a list of all the parse trees, and furthermore, it isn't clear what to do with the list once it has ben constructed. This list may be so numerous that it is probably not the most convenient representation for communication with the semantic and pragmatic processing modules. In this paper we propose some methods for dealing with syntactic ambiguity in ways that take advantage of certain regularities among the alternative parse trees. These regularities will be expressed as linear combinations of ATN networks, and also as sums and products of formal power series. We will suggest some ways that practical processor can take advantage of this modularity in order to deal more efficiently with combinatoric ambiguity. In particular, we will show how a processor can efficiently compute the ambiguity of an input sentence (or any portion thereof). Furthermore, we will show how to compile certain grammars into a form that can be processed more efficiently. In some cases, including the "every way ambiguous" grammar (e.g., conjunction, prepositional phrases, noun-noun modification), processing time will be reduced from O9n^3) to O(n). Finally, we will show how to uncompile certain highly optimized grammars into a form suitable for linguistic analysis.
Anti-inflammatory glucocorticoid action: inhibition of griPGHS, a new cyclooxygenase. (1993)

Our understanding of the anti-inflammatory actions of glucocorticoid hormones has significantly advanced in the past year with the discovery of a second cyclooxygenase gene which we call 'glucocorticoid-regulated inflammatory prostaglandin G/H synthase' (griPGHS). In mouse fibroblasts and human monocytes levels of griPGHS mRNA and protein rise dramatically in response to growth factors, cytokines, and oncogene activation. These inductions are markedly suppressed by the glucocorticoid hormone, dexamethasone. This stands in contrast to the behavior of the previously cloned cyclooxygenase (PGHS), which appears to be constitutively expressed. Thus far, data show that griPGHS is increased in many other systems where prostaglandin biosynthesis is regulated, including models of inflammation, tissue injury, and hormonal control of reproductive processes. Thus, griPGHS is likely to be a key mediator of many clinically relevant processes and as such represents an important target for both steroidal and nonsteroidal anti-inflammatory agents.
Granzyme Release and Caspase Activation in Activated Human T-Lymphocytes (1998)

Recently it has been reported that caspase-3 activation occurs in stimulated T-lymphocytes without associated apoptosis (Miossec, C., Dutilleul, V., Fassy, F., and Diu-Hercend, A. (1997) J. Biol. Chem. 272, 13459-13462). To explore this phenomenon, human peripheral blood lymphocytes (PBLs) were stimulated with mitogenic lectins or anti-CD3 antibody, and the proteolytic processing of different caspases and caspase substrates was analyzed by immunoblotting. Proteolytic processing of caspases-3 and -7 and the caspase substrates poly(ADP-ribose) polymerase, GDP dissociation inhibitor, and PKCdelta was observed when PBLs were activated in vitro, and lysates were prepared using RIPA buffer which contains 1% Nonidet P-40, 0.5% deoxycholate, and 0.1% SDS. In contrast, when a lysis buffer containing 2% SDS was used, the caspases remained in their zymogen pro-forms, and no proteolytic processing of caspase substrates was detected. Moreover, in experiments using intact cells and a cell-permeable fluorigenic caspase substrate, no caspase activity was observed in activated T-cells, whereas it was clearly detected when PBLs were treated with the apoptosis-inducing anticancer drug etoposide. Since the granzyme B is a direct activator of caspase-3 and its expression is induced following T-cell activation, we tested the effects of anti-GraB, an engineered serpin that specifically inhibits GraB. When the activated T-lymphocytes were lysed in RIPA buffer containing anti-GraB, no proteolytic processing or activation of caspase-3 was observed, strongly suggesting that release of GraB or similar proteases from their storage sites in cytotoxic granules during the lysis procedure is responsible for caspase activation. These findings demonstrate that T-cells do not process caspases upon activation and caution about the method of cell lysis used when studying granzyme-expressing cells.
Sport in amsterdam, olympism and other influences: the inter‐war years (2000)

(2000). Sport in amsterdam, olympism and other influences: the inter‐war years. The International Journal of the History of Sport: Vol. 17, No. 4, pp. 141-152.
Protein kinase CK2 signal in neoplasia. (2001)

Protein kinase CK2 (previously known as casein kinase II) is a protein serine/threonine kinase that has been implicated in cell growth and proliferation. The focus of this review is on the apparent role of CK2 in cancer. Studies from several laboratories have shown a dysregulated expression of the kinase in tumors. Nuclear matrix and chromatin appear to be key sites for signaling of the CK2 activity in relation to cell growth. Several types of growth stimuli produce a common downstream response in CK2 by enhancing its nuclear shuttling. The neoplastic change is also associated with changes in intracellular localization of the kinase so that a higher nuclear localization is observed in tumor cells compared with normal cells. Experimental studies suggest that dysregulated expression of the alpha subunit of CK2 imparts an oncogenic potential in the cells such that in cooperation with certain oncogenes it produces a profound enhancement of the tumor phenotype. Recent studies have provided evidence that overexpression of CK2 in tumor cells is not simply a reflection of tumor cell proliferation alone but additionally may reflect the pathobiological characteristics of the tumor. Of considerable interest is the possibility that CK2 dysregulation in tumors may influence the apoptotic activity in those cells. Approaches to interfering with the CK2 signal may provide a useful means for inducing tumor cell death.
Prostaglandin-Producing Suppressor Cells in Hodgkin's Disease (1977)

We examined the role of a prostaglandin-producing suppressor cell in the hyporesponsiveness to phytohemagglutinin seen in Hodgkin's disease. Addition of indomethacin to phytohemagglutinin cultures of lymphocytes from six patients with Hodgkin's disease resulted in an increase of 182 +/- 60 per cent in 3H-thymidine incorporation versus a 44 +/- 18% increase in 29 controls (mean +/- S.D., P less than 0.001). Without indomethacin the mean response of the lymphocytes in Hodgkin's disease was 48% of that of control. With indomethacin it was 94% of the control value. Phytohemagglutinin cultures of Hodgkin-disease lymphocytes produced approximately fourfold more prostaglandin E2 after 48 hours than did normal lymphocytes (P less than 0.02). Removal of glass-adherent cells markedly decreased the enhancement seen with indomethacin; it reduced prostaglandin E2 production by more than 80% and eliminated the differences in response to phytohemagglutinin between Hodgkin-disease and normal lymphocytes. Thus, a glass-adherent, prostaglandin-producing suppressor cell is responsible for the hyporesponsiveness to phytohemagglutinin seen with Hodgkin-disease lymphocytes.
Subtype-Specific Alterations of γ-Aminobutyric Acid and Glutamatein Patients With Major Depression (2004)

The study replicates the findings of decreased GABA concentrations in the occipital cortex of subjects with MDD. It also demonstrates that there is a change in the ratio of excitatory-inhibitory neurotransmitter levels in the cortex of depressed subjects that may be related to altered brain function. Last, the combined data set suggests that magnetic resonance spectroscopy GABA measures may serve as a biological marker for a subtype of MDD.
The Effect of Epinephrine, Glucagon, and the Nutritional State on the Oxidation of Branched Chain Amino Acids and Pyruvate by Isolated Hearts and Diaphragms of the Rat (1973)

The effect of epinephrine and glucagon on W02 production from C-l-labeled branched chain amino acids, [I-W]pyruvate, [1-Wlalanine, and [U-14Clglucose, was studied in isolated diaphragms and petiused hearts.The tissues were obtained from rats fed ad libitum or fasted for 48 hours.Epinephrine (10m4 M) stimulated *4CO~ production from Ieuciue, valine, and alanine by hemidiaphragms of fasted rats incubated without substrate, but not by hemidiaphragms of rats fed ad libifum.The oxidation of histidine was not atIected by epinephrine.Epinephrine (10m5 to lob6 M) stimulated branched chain amino acid oxidation by hearts of fed or fasted rats during perfusion without substrate.The addition of 5.5 mu glucose to the perfusion medium abolished the stimulatory effect of epinephrine on branched chain amino acid oxidation.The addition of pyruvate markedly inhibited the oxidation of branched chain amino acids by perfused hearts, and abolished the stimulatory effect of epinephrine on this process.Glucagon (2 X 1OV to 5 X lo* M) stimulated branched chain amino acid oxidation by hearts of fasted rats perfused without additional substrate.Insulin added to glucagon caused no further stimulation of leucine oxidation.Glucagon did not stimulate leucine oxidation by hearts of fed rats, nor by hearts of fasted rats perfused with glucose (5.5 mM) or pyruvate (20 mM).Glucagon did not affect branched chain amino acid oxidation by diaphragms.N6, 02'-Dibutyryl adenosine 3',5'monophosphate (10-Z to 10m3 M) was mildly inhibitory.Hearts and diaphragms of fed rats oxidized pyruvate much faster than those of fasted rats.Epinephrine (10e6 to 10m6 M) stimulated the myocardial oxidation of pyruvate and alanine.Epinephrine (10m4 to 10e5 M) stimulated the uptake and oxidation of pyruvate by diaphragms of fed or fasted rats, but diaphragms of fed rats were more responsive to this effect of epinephrine than those of fasted rats.
Engineering Chimeric Antigen Receptor T-Cells for Racing in Solid Tumors: Don’t Forget the Fuel (2017)

T-cells play a critical role in tumor immunity. Indeed, the presence of tumor-infiltrating lymphocytes is a predictor of favorable patient prognosis for many indications and is a requirement for responsiveness to immune checkpoint blockade therapy targeting programmed cell death 1. For tumors lacking immune infiltrate, or for which antigen processing and/or presentation has been downregulated, a promising immunotherapeutic approach is chimeric antigen receptor (CAR) T-cell therapy. CARs are hybrid receptors that link the tumor antigen specificity and affinity of an antibody-derived single-chain variable fragment with signaling endodomains associated with T-cell activation. CAR therapy targeting CD19 has yielded extraordinary clinical responses against some hematological tumors. Solid tumors, however, remain an important challenge to CAR T-cells due to issues of homing, tumor vasculature and stromal barriers, and a range of obstacles in the tumor bed. Protumoral immune infiltrate including T regulatory cells and myeloid-derived suppressor cells have been well characterized for their ability to upregulate inhibitory receptors and molecules that hinder effector T-cells. A critical role for metabolic barriers in the tumor microenvironment (TME) is emerging. High glucose consumption and competition for key amino acids by tumor cells can leave T-cells with insufficient energy and biosynthetic precursors to support activities such as cytokine secretion and lead to a phenotypic state of anergy or exhaustion. CAR T-cell expansion protocols that promote a less differentiated phenotype, combined with optimal receptor design and coengineering strategies, along with immunomodulatory therapies that also promote endogenous immunity, offer great promise in surmounting immunometabolic barriers in the TME and curing solid tumors.
Arabidopsis ovule is the target for Agrobacterium in planta vacuum infiltration transformation (1999)

The visual marker GUS has been utilized in this study to understand the Arabidopsis thaliana vacuum infiltration transformation process by Agrobacterium tumefaciens. High transformation frequencies of up to 394 transgenic seeds per infiltrated plant were achieved. The results showed that the majority of the transgenic seeds from single infiltrated plants were from independent transformation events based on Southern analysis, progeny segregation, distribution of transgenic seeds throughout the infiltrated plants and the microscopic analysis of GUS expression in ovules of infiltrated plants. GUS expression in mature pollen and anthers was monitored daily from 0 to 12 days post-infiltration. In addition, all ovules from a single infiltrated plant were examined every other day. GUS expression frequencies of up to 1% of pollen were observed 3-5 days post-infiltration, whereas frequencies of up to 6% were detected with ovules of unopened flowers 5-11 days post-infiltration. Most importantly, transgenic seeds were obtained only from genetic crosses using infiltrated plants as the pollen recipient but not the pollen donor, demonstrating Agrobacterium transformation through the ovule pathway.
The soluble hyaluronidase from bull testes is a fragment of the membrane‐bound PH‐20 enzyme (1997)

The membrane-bound PH-20 hyaluronidase is known to be essential for fertilization. Here we addressed the question whether the soluble hyaluronidase from bull teste is related to the PH-20 polypeptide. The sequence of the membrane-bound PH-20 hyaluronidase from bovine sperm was determined via cDNA cloning. In parallel, from a commercial preparation of bovine hyaluronidase the major 60-kDa form was purified to apparent homogeneity. The soluble enzyme was digested with two different proteases and with cyanogen bromide and the amino acid sequence of 44 different fragments was determined. All the peptide sequences could be aligned to the sequence deduced from the cloned cDNAs. Our results thus show that the soluble 60-kDa hyaluronidase from bovine testes is a glycoprotein derived from the sperm PH-20 enzyme. As compared to the primary translation product of the PH-20 mRNA, it lacks the signal peptide at the amino terminus and 56 amino acids at the carboxyl end. These results demonstrate that the soluble 60-kDa enzyme is a fragment of the PH-20 hyaluronidase. It is currently not known whether the soluble testes hyaluronidase has a distinct biological function.