gebhart/patrepeval huggingface dataset:
Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcγRIIIa gene (2002)

Given that the FcgammaRIIIa receptor 158V allotype displays a higher affinity for human immunoglobulin G1 and increased antibody-dependent cellular cytotoxicity, the aim of this study was to determine the influence of that FCGR3A polymorphism on the therapeutic response to rituximab, an anti-CD20 humanized immunoglobulin G1 increasingly used in the treatment of non-Hodgkin lymphomas. The FCGR3A-158V/F genotype was determined in 49 patients having received rituximab for a previously untreated follicular non-Hodgkin lymphoma. The clinical response and the disappearance of the BCL2-JH gene rearrangement in both peripheral blood and bone marrow were evaluated at 2 months (M2) and at 1 year (M12). The study population consisted of 20% FCGR3A-158V homozygous patients, 35% FCGR3A-158F homozygous patients, and 45% heterozygous patients (FCGR3A-158F carriers). The objective response rates at M2 and M12 were 100% and 90%, respectively, in FCGR3A-158V homozygous patients compared with 67% (P =.03) and 51% (P =.03), respectively, in FCGR3A-158F carriers. A disappearance of the BCL2-JH gene rearrangement in both peripheral blood and marrow was observed at M12 in 5 of 6 of homozygous FCGR3A-158V patients compared with 5 of 17 of FCGR3A-158F carriers (P =.03). The homozygous FCGR3A-158V genotype was confirmed to be the single parameter associated with clinical and molecular responses by multivariate analysis. This study showed an association between the FCGR3A genotype and clinical and molecular responses to rituximab. This finding will certainly give rise to new pharmacogenetic approaches to the management of patients with non-Hodgkin lymphomas.
Persistent chlamydiae: from cell culture to a paradigm for chlamydial pathogenesis (1994)

Chlamydiae are medically important bacteria responsible for a wide range of human infections and diseases. Repeated episodes of infection promote chronic inflammation associated with detrimental immune system-mediated pathologic changes. However, the true nature of chlamydial pathogenesis may encompass repeated infection superimposed upon persistent infection, which would allow for heightened immune reactivity. During the course of chlamydial infection, numerous host elaborated factors with inhibitory or modifying effects may cause alterations in the chlamydia-host cell relationship such that the organism is maintained in a nonproductive stage of growth. Abnormal or persistent chlamydiae have been recognized under a variety of cell culture systems. The numerous factors associated with altered growth suggest an innate flexibility in the developmental cycle of chlamydiae. This review evaluates in vitro studies of chlamydial persistence and correlates these model systems to features of natural chlamydial disease.
Calcium-regulated exocytosis is required for cell membrane resealing. (1995)

Using confocal microscopy, we visualized exocytosis during membrane resealing in sea urchin eggs and embryos. Upon wounding by a laser beam, both eggs and embryos showed a rapid burst of localized Ca(2+)-regulated exocytosis. The rate of exocytosis was correlated quantitatively with successfully resealing. In embryos, whose activated surfaces must first dock vesicles before fusion, exocytosis and membrane resealing were inhibited by neurotoxins that selectively cleave the SNARE complex proteins, synaptobrevin, SNAP-25, and syntaxin. In eggs, whose cortical vesicles are already docked, vesicles could be reversibly undocked with externally applied stachyose. If cortical vesicles were undocked both exocytosis and plasma membrane resealing were completely inhibited. When cortical vesicles were transiently undocked, exposure to tetanus toxin and botulinum neurotoxin type C1 rendered them no longer competent for resealing, although botulinum neurotoxin type A was still ineffective. Cortical vesicles transiently undocked in the presence of tetanus toxin were subsequently fusion incompetent although to a large extent they retained their ability to redock when stachyose was diluted. We conclude that addition of internal membranes by exocytosis is required and that a SNARE-like complex plays differential roles in vesicle docking and fusion for the repair of disrupted plasma membrane.
Interferon-Tau and Progesterone Regulate Ubiquitin Cross-Reactive Protein Expression in the Ovine Uterus1 (2000)

Ubiquitin cross-reactive protein (UCRP) is a functional ubiquitin homolog synthesized by the ruminant endometrium in response to conceptus-derived interferon-tau (IFNtau). Progesterone is required for IFNtau to exert antiluteolytic actions on the endometrium. Therefore, this study was designed to determine whether progesterone is requisite for IFNtau induction of UCRP expression within the ovine uterus. Cyclic ewes were ovariectomized and fitted with intrauterine (i.u.) catheters on Day 5 and treated daily with steroids (i.m.) and protein (i.u.) as follows: 1) progesterone (P, Days 5-24) and control serum proteins (CX, Days 11-24); 2) P and ZK 137.316 (ZK; progesterone receptor antagonist, Days 11-24) and CX proteins; 3) P and recombinant ovine IFNtau (roIFNtau, Days 11-24); or 4) P and ZK and roIFNtau. All ewes were hysterectomized on Day 25. In P-treated ewes, roIFNtau increased endometrial UCRP mRNA and protein levels. However, administration of ZK to ewes ablated roIFNtau induction of UCRP. Recombinant ovine IFNtau induced expression of UCRP mRNA in progestinized endometrial luminal (LE) and glandular (GE) epithelium as well as in both stratum compactum and spongiosum layers of the stroma (ST). Progesterone receptor protein was located in endometrial ST, but not in LE and GE from these ewes. Results support the hypothesis that progesterone is required for IFNtau induction of type I IFN-responsive genes, such as UCRP, in the ruminant uterus.
Selection and combination of various endovascular techniques in the treatment of giant aneurysms (1992)

Between April, 1989, and January, 1991, a total of 19 cases of giant aneurysm were treated by the endovascular approach. The patients included seven males and 12 females aged 15 to 72 years. Detachable balloons, occlusion coils, and ethylene vinyl alcohol copolymer liquid were used as embolic materials. In seven cases, thrombosis of the aneurysmal sac and/or base was achieved while sparing the parent arterial flow, complete obliteration of the aneurysm was achieved in four of these. Of these four patients, the thrombotic material was a detachable balloon in two, a combination of a detachable balloon and coils in one, and occlusion liquid in one. In the other three cases, complete occlusion was not achieved; one aneurysm was occluded with a detachable balloon and two with coils. In 11 patients, the parent artery was occluded either by trapping or by proximal arterial occlusion, and all patients showed complete occlusion of the aneurysms. In one patient, a combined bypass procedure and parent artery occlusion was performed. Among the 19 cases in this series there were four transient ischemic attacks, one reversible ischemic neurological deficit, and one death due to aneurysmal rupture during the procedure. Two patients died in the follow-up period, one from pneumonia 2 months postoperatively and the other from acute cardiac failure 2 weeks following surgery. Both deaths were unrelated to the endovascular procedure. It is concluded that the endovascular treatment of giant aneurysms remains difficult because of the large and irregular shape of the aneurysmal base and thrombus in the aneurysmal sac. The proper selection and combination of the available endovascular techniques is therefore of critical importance.
Oculomucocutaneous changes as paraneoplastic syndromes. (1996)

Bullous dermatoses such as erythema exsudativum multiform major (EEMM) and bullous pemphigoid can lead to severe ocular involvement. In rare cases, both diseases develop as paraneoplastic syndromes. The immunopathologic mechanisms are discussed. A 69-year-old woman with non-Hodgkin's lymphoma (NHL) of grade IIIb developed EEMM while under systemic treatment with Fluconazole, Ofloxacin, and/or a combination of sulfamethoxazole and trimethoprim after polychemotherapy. In the eye, conjunctival necrosis with sicca syndrome led to Staphylococcus aureus-induced corneal superinfection, perforation, and consecutive keratoplasty à chaud. The patient died 6 weeks after the first presentation. A 44-year-old man with NHL of grade IVa after polychemotherapy developed a bullous pemphigoid affecting the skin, mucous membranes, and both eyes while under systemic treatment with sulfamethoxazole and trimethoprim. Although the underlying malignancy responded well to chemotherapy, the ocular manifestations of the paraneoplastic systemic syndrome slowed down only on treatment with cyclosporin A but not following therapy with azathioprine and cyclophosphamide. Therapy could not stop cicatrization and keratinization of the conjunctiva and cornea. An occult malignancy should be excluded in acute and chronic oculomucocutaneous syndromes. The prognosis for the eye seems to be poor because of the rapid course and the ineffectiveness of therapy as demonstrated in the present cases.
In vivo blockade of TNF-α by intravenous infusion of a chimeric monoclonal TNF-α antibody in patients with rheumatoid arthritis. Short term cellular and molecular effects (1996)

Due to the unknown etiology of RA, specific treatment is not available. Recently, in a double-blinded, placebo-controlled clinical trial, in vivo blockade of TNF-alpha by a single infusion of a chimeric TNF-alpha-blocking mAb, cA2, has proven to be highly effective in the treatment of RA. In parallel to this trial, we tested the consequences of cA2 infusion in ex vivo and in vitro experiments. In this paper, we describe an increase in CD4+ and CD8+ T lymphocyte counts on day 1 and a marked decrease in monocyte counts preferentially on day 7 after cA2 treatment, without major changes in B lymphocyte or NK cell counts. In addition, we found an increased responsiveness of PBMC to CD28 mAb/PMA, but not to CD3 mAb, superantigen staphylococcus enterotoxin B, or PHA on day 1 after infusion. The increase in DNA synthesis of PBMC was paralleled by increased IL-2 mRNA and IL-4 mRNA expression and IL-2 protein secretion in culture supernatants after in vitro stimulation of PBMC with CD28 mAb/PMA. In PBMC, we did not find any significant changes in mRNA or protein expression of CD28 Ag or CD28 ligands, B7-1 and B7-2. Serum concentrations of IL-1 beta, IL-6, and soluble CD14 were significantly diminished after in vivo TNF-alpha blockade. We did not see relevant changes in granulocyte function in vitro after cA2 infusion. Finally, we observed a statistically significant decrease in slCAM-1 molecules in the serum of patients treated with verum compared with that in the serum of subjects given placebo. This change in slCAM-1 concentration was evident on days 1 and 7 after the infusion of 10 mg/kg cA2, whereas it occurred only on day 7 in the serum of patients treated with the low dose (1 mg/kg) of cA2.
Carbohydrate selectin inhibitor CY-1503 reduces neutrophil migration and reperfusion injury in canine pulmonary allografts. (1997)

Our observations indicate that selectin inhibition effectively reduces PMN adhesion, migration, and subsequent reperfusion injury in preserved canine lung allografts.
The Role of 11Beta-Hydroxysteroid Dehydrogenase in Metabolic Disease and Therapeutic Potential of 11Beta-HSD1 Inhibitors (2008)

Glucocorticoids play an essential role in the regulation of multiple physiological processes, including energy metabolism, maintenance of blood pressure and stress responses, as well as cognitive functions. On a tissue-specific level, glucocorticoid action is controlled by 11beta-hydroxysteroid dehydrogenase enzymes. The type 1 enzyme (11beta-HSD1) is a NADP(H)-dependent bidirectional enzyme in vitro and reduces cortisone to active cortisol in vivo. 11beta-HSD1 is expressed in many tissues including the liver, adipose and skeletal muscles. Chronically elevated local glucocorticoid action as a result of increased 11beta-HSD1 activity has been associated with the metabolic syndrome, which is characterized by obesity, insulin resistance, type 2 diabetes and cardiovascular complications. Recent studies indicate that the inhibition of 11beta-HSD1 mitigates the adverse effects of excessive glucocorticoid levels on metabolic parameters and provides promising opportunities for the development of therapeutic interventions. This review discusses recently disclosed 11beta-HSD1 inhibitors and their potential for the treatment of metabolic disorders.
Three-Dimensional Silicone Device Fabrication and Interconnection Scheme for Microfluidic Applications Using Sacrificial Wax Layers (2000)

Abstract A simple room-temperature procedure is reported herein for formation of true three-dimensionality of “microfluidic components” and complete microfluidic systems in silicone elastomer, this is achieved by molding the plastic to simply encapsulate a pre-formed network of sacrificial wax threads or other connected wax configurations which are ultimately to become micro channels, microfluidic components and cavities in the plastic motherboard. When these wax sacrificial areas are etched away with acetone, precise cavities, channels, and capillaries result with direct arbitrary three-dimensionality. This method leads also to a simple and effective external interconnection scheme where ordinary fused silica tubes may be press-fitted into the surface opening to withstand high pressure. An array of micro channels having circular cross sections with diameters of 100, 150 and 200 microns, membrane type valves, pinch valves, mixing chambers and reservoirs for fluid storage were molded in silicone elastomer using wax filaments. The wax filaments were dissolved in acetone after the silicone elastomer became hardened, leaving the micro channels, valves, mixing chambers and reservoirs in the silicone elastomer. This scheme gives the flexibility of allowing multi stacks of components (motherboards) while being able to control the channel lengths within the stacks as desired.
Temperature Affects Expansion Rate of Maize Leaves without Change in Spatial Distribution of Cell Length (Analysis of the Coordination between Cell Division and Cell Expansion) (1995)

We have analyzed the way in which temperature affects leaf elongation rate of maize (Zea mays L.) leaves, while spatial distributions (observed at a given time) of cell length and of proportion of cells in DNA replication are unaffected. We have evaluated, in six growth chamber experiments with constant temperatures (from 13 to 34[deg]C) and two field experiments with fluctuating temperatures, (a) the spatial distributions of cell length and of leaf elongation rate, and (b) the distribution of cell division, either by using the continuity equation or by flow cytometry. Leaf elongation rate was closely related to meristem temperature, with a common relationship in the field and in the growth chamber. Cell division and cell elongation occurred in the first 20 and 60 mm after the ligule, respectively, at all temperatures. Similar quantitative responses to temperature were observed for local cell division and local tissue expansion rates (common x intercept and normalized slope), and both responses were spatially uniform over the whole expanding zone (common time courses in thermal time). As a consequence, faster cell elongation matched faster cell division rate and faster elongation was compensated for by faster cell displacement, resulting in temperature-invariant profiles of cell length and of proportion of dividing cells. Cell-to-cell communication, therefore, was not necessary to account for coordination.
Phosphorothioate Analogues of Nucleotides—Tools for the Investigation of Biochemical Processes (1983)

Abstract Nucleoside phosphorothioates are analogues of nucleotides with a wide range of applications. Thus, on the one hand, in many but not all cases they are more stable against hydrolysis than the unmodified nucleotides—a property which they share with other nucleotide analogues. On the other hand, however, they are good substrates for many, but not all reactions where the nucleotide or the phosphorothioate group is transferred to an acceptor other than H 2 O. As a consequence, once incorporated into a system such as DNA, phosphorothioates cannot be easily removed. What makes these compounds unique to a certain extent is the chirality at the phosphorus center if two nonequivalent residues are linked to the phosphorothioate group. This opens the way for the use of these compounds to investigate stereochemical aspects of enzymatic reactions. In addition to these properties, there are those expected from exchange of an oxygen for a sulfur atom in a phosphate group, e.g. the increased affinity towards mercury derivatives and the large chemical shift of the 31 P‐NMR sinals. If one considers how many biologically interesting compounds contain phosphate groups, the considerable interest in these nucleotide analogues is not surprising.
Combining seeking safety with sertraline for PTSD and alcohol use disorders: A randomized controlled trial. (2015)

Results support the combining of a cognitive-behavioral therapy and sertraline for PTSD/AUD. Clinically significant reductions in both PTSD and AUD severity were achieved and sustained through 12-months follow-up, Moreover, greater mean improvement in PTSD symptoms was observed across all follow-up assessments in the SS plus sertraline group. (PsycINFO Database Record
Factors in Xenograft Rejection (1999)

Important mechanisms underlying immediate xenograft loss by hyperacute rejection (HAR), in the pig-to-primate combination, have been recently delineated. There are now several proposed therapies that deal with the problem of complement activation and xenoreactive natural antibody (XNA) binding to the vasculature that have been shown to prevent HAR. However, vascularized xenografts are still lost, typically within days, by delayed xenograft rejection (DXR), alternatively known as acute vascular rejection (AVR). This process is characterized by endothelial cell (EC) perturbation, localization of XNA within the graft vasculature, host NK cell and monocyte activation with platelet sequestration and vascular thrombosis. Alternative immunosuppressive strategies, additive anti-complement therapies with the control of any resulting EC activation processes and induction of protective responses have been proposed to ameliorate this pathological process. In addition, several potentially important molecular incompatibilities between activated human coagulation factors and the natural anticoagulants expressed on porcine EC have been noted. Such incompatibilities may be analogous to cross-species alterations in the function of complement regulatory proteins important in HAR. Disordered thromboregulation is potentially relevant to the progression of inflammatory events in DXR and the disseminated intravascular coagulation seen in primate recipients of porcine renal xenografts. We have recently demonstrated the inability of porcine tissue factor pathway inhibitor (TFPI) to adequately neutralize human factor Xa (FXa), the aberrant activation of both human prothrombin and FXa by porcine EC and the failure of the porcine natural anticoagulant, thrombomodulin to bind human thrombin and hence activate human protein C. The enhanced potential of porcine von Willebrand factor to associate with human platelet GPIb has been demonstrated to be dependent upon the isolated A1 domain of von Willebrand factor. In addition, the loss of TFPI and vascular ATPDase/CD39 activity following EC activation responses would potentiate any procoagulant changes within the xenograft. These developments could exacerbate vascular damage from whatever cause and enhance the activation of platelets and coagulation pathways within xenografts resulting in graft infarction and loss. Analysis of these and the other putative factors underlying DXR should lead to the development and testing of genetic approaches that, in conjunction with selected pharmacological means, may further prolong xenograft survival to a clinically relevant extent.
Gene transfer demonstrates that muscle is not a primary target for non-cell-autonomous toxicity in familial amyotrophic lateral sclerosis (2006)

Amyotrophic lateral sclerosis (ALS) is a fatal, progressive paralysis arising from the premature death of motor neurons. An inherited form is caused by a dominant mutation in the ubiquitously expressed superoxide dismutase (SOD1). SOD1 mutant expression within motor neurons is a determinant of onset and early disease, and mutant accumulation within microglia accelerates disease progression. Muscle also is a likely primary source for toxicity, because retraction of motor axons from synaptic connections to muscle is among the earliest presymptomatic events. To test involvement of muscle in ALS, viral delivery of transcription-mediated siRNA is shown to suppress mutant SOD1 accumulation within muscle alone but to be insufficient to maintain grip strength, whereas delivery to both motor neurons and muscle is sufficient. Use of a deletable mutant gene to diminish mutant SOD1 from muscle did not affect onset or survival. Finally, follistatin expression encoded by adeno-associated virus chronically inhibited myostatin and produced sustained increases in muscle mass, myofiber number, and fiber diameter, but these increases did not affect survival. Thus, SOD1-mutant-mediated damage within muscles is not a significant contributor to non-cell-autonomous pathogenesis in ALS, and enhancing muscle mass and strength provides no benefit in slowing disease onset or progression.
The Amelogenin C-Terminus Is Required for Enamel Development (2009)

The abundant amelogenin proteins are responsible for generating proper enamel thickness and structure, and most amelogenins include a conserved hydrophilic C-terminus. To evaluate the importance of the C-terminus, we generated transgenic mice that express an amelogenin lacking the C-terminal 13 amino acids (CTRNC). MicroCT analysis of TgCTRNC29 teeth (low transgene number) indicated that molar enamel density was similar to that of wild-type mice, but TgCTRNC18 molar enamel (high transgene number) was deficient, indicating that extra transgene copies were associated with a more severe phenotype. When amelogenin-null (KO) and TgCTRNC transgenic mice were mated, density and volume of molar enamel from TgCTRNCKO offspring were not different from those of KO mice, indicating that neither TgCTRNC18 nor TgCTRNC29 rescued enamel's physical characteristics. Because transgenic full-length amelogenin partially rescues both density and volume of KO molar enamel, it was concluded that the amelogenin C-terminus is essential for proper enamel density, volume, and organization.
Dehydration of Bile Acids and their Derivatives. IX. Oxidation of Methyl 3α-Acetoxy-Δ7-cholenate with Selenium Dioxide (1962)

Abstract Carefully repeated experiments have shown that, contrary to Fieser’s report3), methyl 3α-acetoxy-Δ7-cholenate and some other un-saturated bile acids (5β) listed in Table I give positive results in the selenium dioxide test. This finding was substantiated by the fact that two oxidation products of methyl 3α-acetoxy-Δ7-cholenate were isolated, one of which was proved to be methyl 3α-acetoxy-7ξ, 15ξ-dihydroxy-Δ8(14)-cholenate. It is very interesting to note that, unlike the Δ7-steroids of the 5α-series, not only C7-H, but C15-H of the unsaturated bile acid mentioned above was oxidized with selenium dioxide to give hydroxyl groups, both of which remained without being acetylated under the experimental conditions described.