gebhart/patrepeval huggingface dataset:
Evidence for a graft-versus-tumor effect in a patient treated with marrow ablative chemotherapy and allogeneic bone marrow transplantation for breast cancer (1996)

Graft-versus-leukemia (GvL) has been shown to be an important immune-mediated antitumor effect in hematologic malignancies. It is still unknown whether such an immunemediated antitumor effect has clinical implications in patients with solid tumors. A 32-year-old woman with inflammatory breast cancer received a bone marrow transplant (BMT) from her HLA-identical sibling. During graft-versus-host disease (GvHD) cytotoxic T lymphocytes were grown and tested in a chromium-release assay against B and T lymphocytes of the patient and donor and against a panel of breast cancer cell lines. Resolution of liver metastases was observed simultaneously with clinical GvHD in the first weeks after transplant. In addition, minor histocompatibility antigen (MiHA)-specific and major histocompatibility complex (MHC) class I antigen-restricted cytotoxic T lymphocytes recognizing breast carcinoma target cells were isolated from the blood of the patient. Pretreatment of such target cells with tumor necrosis factor (TNF)-alpha but not with interferon (IFN)-alpha or IFN-gamma increased susceptibility of these cells to lysis by cytotoxic T lymphocytes. Clinical course and in vitro results suggest that a graft-versus-tumor (GvT) effect might exist after allogeneic BMT for breast cancer. However, clinical experience on a larger scale would be required to determine the clinical efficacy of GvT effects in patients with solid tumors.
Isolation of Two Human Tumor Epithelial Cell Lines From Solid Breast Carcinomas<xref ref-type="fn" rid="FN1">2</xref> (1978)

Most of the available human breast tumor cell lines have been derived from pleural effusions. The two cell lines herein described, BT-474 and BT-483, were derived from solid, invasive ductal breast carcinomas. Both are epithelial and neoplastic as judged by their general morphology, their fine structure, and their ability to produce growing nodules in nude mice and colonies in soft agar and methocel. BT-474 and BT-483 are human as expressed by chromosome morphology and aneuploid with a modal number of 55 and 72 chromosomes, respectively. Trypsin-Giemsa banding did not reveal the presence of obvious HeLa markers, and the glucose 6-phosphate dehydrogenase electrophoretic migration pattern was of the B-type. Furthermore, the migration of lactic dehydrogenase, malic dehydrogenase, and 6-phosphogluconate dehydrogenase isoenzymes was consistent with a human pattern and different from that of the mouse, rat, or hamster. Quarterly tests to detect the presence of aerobic and anaerobic mycoplasmas were repeatedly negative. A culture medium containing insulin, increased amounts of amino acids, vitamins, and glucose facilitated the isolation of the tumor cells. Cell replication was maintained with 10% fetal calf serum absorbed with activated charcoal and dextran. No production of alpha-lactalbumin was detected by radioimmunoassays, but high levels of progesterone receptors were found in both cell lines.
The Maze of Vasodilator Response Criteria (2010)

With great interest we read the article of Barst et al. [1]. We agree with their statement that the definition of a positive acute vasodilator response in patients with pulmonary arterial hypertension (PAH) remains controversial. We believe it is very important to minimize this controversy and use uniform criteria when studying the acute pulmonary vasodilator response in patients with PAH.


In their article, Barst and coworkers defined acute response criteria based on a 20% or more decrease in mean pulmonary arterial pressure (mPAP) with no decrease in cardiac index, or on a 25% or more decrease in the pulmonary vascular resistance index (PVRI) with no decrease in cardiac index (the latter only in case of an unrestricted shunt at the ventricular or ductal level). We do not recognise these criteria from previously published reports. A review of the literature provides the following definitions of a positive response to acute pulmonary vasodilator tests:


An mPAP decrease of 20% or more, no decrease in cardiac index and no change or a decrease in the pulmonary-to-systemic vascular resistance ratio [2, 3]


A decrease of more than 20% in both mPAP and PVRI [4, 6]


A fall in total pulmonary resistance of more than 30% [7]


A decrease in mPAP of 10 mmHg or more, reaching an mPAP of 40 mmHg or less and a normal cardiac output [5].




To our knowledge, the criteria used in the current article have not been published previously. The use of different response criteria in different studies results in different prevalences of acute vasodilator response and different predictive values for identifying long-term responders to calcium-channel blocker treatment and patients with improved survival [5].

Furthermore, as a result, data from these studies cannot be compared directly. For example, the prevalence of acute responders among children with PAH (42%) is reported to be higher than among adults (12–26%) [2, 4, 5]. However, because the criteria used differed between children and adults, this comparison does not hold.

We commend Barst and coworkers for their success in comparing the use of different vasodilating agents (inhaled nitric oxide, oxygen, or the combination of the two) for vasodilator testing in children. However, the introduction again of new response criteria prohibits interpretation of these data in the perspective of previously published data.

It is not our intention to discourage the quest for new response criteria aimed at reaching better prediction of treatment effect or survival or at expanding its use to broader patient populations other than those with idiopathic PAH (iPAH) or familial PAH (FPAH). However, in view of the ongoing discussion on the optimal definition of acute response criteria, we strongly advocate presenting the use of new criteria in a manner comparative with the use of previously published criteria.
Epigenetic inactivation of BCL6B , a novel functional tumour suppressor for gastric cancer, is associated with poor survival (2011)

BCL6B plays a pivotal role as a potential tumour suppressor in GC. Detection of methylated BCL6B may serve as an independent biomarker for the prognosis of GC.
Ubiquitin-mediated Processing of NF-κB Transcriptional Activator Precursor p105 (1995)

In most cases, the transcriptional factor NF-kappa B is a heterodimer consisting of two subunits, p50 and p65, which are encoded by two distinct genes of the Rel family. p50 is translated as a precursor of 105 kDa. The C-terminal domain of the precursor is rapidly degraded, forming the mature p50 subunit consisted of the N-terminal region of the molecule. The mechanism of generation of p50 is not known. It has been suggested that the ubiquitin-proteasome system is involved in the process; however, the specific enzymes involved and the mechanism of limited proteolysis, in which half of the molecule is spared, have been obscure. Palombella and colleagues (Palombella, V. J., Rando, O. J., Goldberg, A. L., and Maniatis, T. (1994) Cell 78, 773-785) have shown that ubiquitin is required for the processing in a cell-free system of a truncated, artificially constructed, 60-kDa precursor. They have also shown that proteasome inhibitors block the processing both in vitro and in vivo. In this study, we demonstrate reconstitution of a cell-free processing system and demonstrate directly that: (a) the ubiquitin-proteasome system is involved in processing of the intact p105 precursor, (b) conjugation of ubiquitin to the precursor is an essential intermediate step in the processing, (c) the recently discovered novel species of the ubiquitin-carrier protein, E2-F1, that is involved in the conjugation and degradation of p53, is also required for the limited processing of the p105 precursor, and (d) a novel, approximately 320-kDa species of ubiquitin-protein ligase, is involved in the process. This novel enzyme is distinct from E6-AP, the p53-conjugating ligase, and from E3 alpha, the "N-end rule" ligase.
D-chiro-inositol metabolism in diabetes mellitus. (1993)

D-chiro-inositol is a rare inositol isomer present in inositol phosphoglycans which are proposed mediators of insulin action. To study D-chiro-inositol metabolism in diabetes mellitus, a sensitive and specific assay was developed using negative-ion chemical ionization gas chromatography/mass spectrometry. Median urinary D-chiro-inositol excretion, which was 2.1 mumol/day in nondiabetics, was substantially increased to 12 mumol/day in non-insulin-dependent diabetes (P < 0.0001) and to 74 mumol/day in insulin-dependent diabetes (P < 0.0001). Urinary D-chiro-inositol was strongly correlated with fasting plasma glucose (r = 0.568, P < 0.0001), glycated hemoglobin (r = 0.529, P < 0.0001), and urinary glucose (r = 0.368, P = 0.01). The renal clearance of D-chiro-inositol was selectively elevated in both non-insulin-dependent and insulin-dependent diabetes when compared with the clearances of L-chiro-inositol or myo-inositol and exceeded the glomerular filtration rate in 71% of the diabetics but in none of the nondiabetics. In poorly controlled diabetic patients insulin treatment reduced urinary D-chiro-inositol losses by 63% and increased plasma levels by 8.8-fold. The metabolism of D-chiro-inositol is abnormal in diabetes and appears to be influenced by short- and long-term metabolic control.
In vitro binding of 3,5-di-iodo-L-thyronine to rat liver mitochondria (1994)

In this study we have demonstrated that specific binding sites for 3,5-di-iodo-L-thyronine (3,5-T2) can be detected in rat liver mitochondria. After incubation with the homogenate, liver mitochondria bound only a small portion of [3,5-125I]T2. The addition of a 100-fold excess of unlabelled 3,5-T2 caused the displacement of on average 50-60% of the [3,5-125I]T2 bound. Specific binding of 3,5-T2 to rat liver mitochondria occurred rapidly; a maximum was achieved after 5 min. Maximal binding was obtained at 37 degrees C, while at 0 degrees C and 20 degrees C the values were only slightly lower. Binding was maximal at pH 7.0; mean (+/- S.E.M.) values for the apparent association constant and the binding capacity (calculated at pH 7.0, 0 degrees C and after 30 min of incubation) were 0.5 +/- 0.04 x 10(8) M-1 and 0.4 +/- 0.04 pmol/mg mitochondrial protein respectively. The specificity of binding, examined in competition studies, followed the order: 3,5-T2 > 3,3'-di-iodo-L-thyronine > 3',3,5-tri-iodo-L-thyronine > thyroxine. Other iodothyronines (3',5'-di-iodo-L-thyronine, 3,5-di-iodo-D-thyronine, 3,3',5'-tri-iodo-L-thyronine, 3-iodo-L-thyronine and 3,5-di-iodothyroacetic acid) showed little or no competition. This suggests that the specific 3,5-T2 binding sites could be of biological relevance with respect to the understanding of the mechanism of physiological action of thyroid hormones at the cellular level.
Quantitative Multiplex Methylation-Specific PCR Analysis Doubles Detection of Tumor Cells in Breast Ductal Fluid (2006)

Compared with cytology, QM-MSP doubled the sensitivity of detection of cancer. This study provides proof of principle by showing the advantages of using methylation analyses to query cytologic specimens and indicates its potential use in diagnosis and in stratifying risk.
New insights into progressive multifocal leukoencephalopathy (2004)

Advances in the understanding of JC virus biology have shed new light on the pathogenesis of progressive multifocal leukoencephalopathy, and on its possible role in cerebellar atrophy in HIV-infected individuals. Findings on the cellular immune response against the virus have direct implications for patient management, and may lead to new forms of immunotherapies for progressive multifocal leukoencephalopathy. An animal model of progressive multifocal leukoencephalopathy in non-human primates will facilitate the development of novel therapeutic strategies.
Recent progress in the use of monoclonal antibodies for imaging and therapy. (1993)

Despite their availability since 1975, monoclonal antibodies (MAbs) have failed to make a significant impact in the clinical treatment of patients outside of diagnostic assays for the measurement of tumor markers. Recently, however, studies have appeared demonstrating that MAb-directed imaging techniques may have a meaningful role to play in the diagnosis and treatment of patients with solid tumors such as colorectal cancer and malignant melanoma. Furthermore, second generation MAbs are appearing that mediate more specific binding characteristics, and experimental studies have suggested that genuine antitumor activity may not be far away. Finally, the recent development of newer molecules, such as chimeric and human antibodies, may lead to significant advances in MAb use. Specifically, allergic reactions to murine antibodies can be reduced or avoided altogether, and repeated doses can be administered safely. These newer MAbs appear to mediate cell lysis more efficiently and have been combined with chemotherapeutic agents and cell toxins. Greater understanding of host responses to MAbs and the development of anti-idiotype and anti-anti-idiotype antibodies have led to clinical trials that, it is hoped, will confirm the place of MAb therapy in clinical oncology.
Cloning, expression, and DNA sequence analysis of genes encoding nontypeable Haemophilus influenzae high-molecular-weight surface-exposed proteins related to filamentous hemagglutinin of Bordetella pertussis (1992)

A group of high-molecular-weight surface-exposed proteins of nontypeable Haemophilus influenzae are major targets of human serum antibody (S. J. Barenkamp and F. F. Bodor, Pediatr. Infect. Dis. J. 9:333-337, 1990). To further characterize these proteins, we cloned and sequenced genes encoding two related high-molecular-weight proteins from a prototype nontypeable Haemophilus strain. The gene encoding a 120-kDa Haemophilus protein consisted of a 4.4-kbp open reading frame, and the gene encoding a 125-kDa protein consisted of a 4.6-kbp open reading frame. The first 1,259 bp of the two genes were identical. Thereafter, the sequences began to diverge, but overall they were 80% identical, and the derived amino acid sequences showed 70% identity. A protein sequence homology search demonstrated similarity between the derived amino acid sequences of both cloned genes and the derived amino acid sequence of the gene encoding filamentous hemagglutinin, a surface protein produced by the gram-negative pathogen Bordetella pertussis. Antiserum raised against a recombinant protein encoded by the 4.6-kbp open reading frame recognized both the 120- and the 125-kDa proteins in the prototype strain as well as antigenically related high-molecular-weight proteins in 75% of a collection of 125 epidemiologically unrelated nontypeable H. influenzae strains. The antiserum directed against the recombinant protein also recognized purified filamentous hemagglutinin. A murine monoclonal antibody to filamentous hemagglutinin recognized both the 120-kDa and the 125-kDa protein in the prototype strain as well as proteins identical to those recognized by the recombinant-protein antiserum in 35% of the nontypeable H. influenzae strain collection. Thus, we have identified and partially characterized a group of highly immunogenic surface-exposed proteins of nontypeable H. influenzae which are related to the filamentous hemagglutinin of B. pertussis.
Structure and orientation of the antibiotic peptide magainin in membranes by solid‐state nuclear magnetic resonance spectroscopy (1993)

Magainin 2 is a 23-residue peptide that forms an amphipathic alpha-helix in membrane environments. It functions as an antibiotic and is known to disrupt the electrochemical gradients across the cell membranes of many bacteria, fungi, and some tumor cells, although it does not lyse red blood cells. One- and two-dimensional solid-state 15N NMR spectra of specifically 15N-labeled magainin 2 in oriented bilayer samples show that the secondary structure of essentially the entire peptide is alpha-helix, immobilized by its interactions with the phospholipids, and oriented parallel to the membrane surface.
Patellar tendinosis (jumper's knee): findings at histopathologic examination, US, and MR imaging. Victorian Institute of Sport Tendon Study Group. (1996)

PURPOSE: To determine the histopathologic findings of patellar tendinosis ("jumper's knee") demonstrated with ultrasonography (US) and magnetic resonance (MR) imaging. MATERIALS AND METHODS: Twenty-four athletes (28 knees) with jumper's knee (23 men, one women; mean age, 30.9 years) scheduled to undergo open tenotomy underwent US patellar tendon examination. Seventeen patients (19 knees) also underwent MR imaging. Tissue was obtained for histopathologic examination in all 28 cases. Eleven age-, height-, and weight-matched athletes (22 knees) without previous knee symptoms served as control subjects for the US examination. Control material for histopathologic examination was obtained in 20 cadavers (39 knees). Data were analyzed with standard statistical methods. RESULTS: MR imaging and US both revealed an abnormal zone at the proximal patellar tendon attachment. Histopathologic examination revealed mucoid degeneration in all tendons in patients and in 8% (three of 39) of tendons in cadavers (P < .01). CONCLUSION: Jumper's knee is characterized by consistent changes at MR imaging, US, and histopathologic examination and is appropriately described as patellar tendinosis.
Streptococcal infections: clinical aspects, microbiology, and molecular pathogenesis. (2000)

Introduction 1: Floyd Denny: History of Streptococcal Infections 2: Dennis Stevens: Group A Streptococci: Virulence Factors, Pathogenesis and the Spectrum of Clinical Infection 3: Joseph Ferretti and Patrick Cleary: Group A Streptococcal Genetics 4: Patrick Schlievert, Roggiani, Aris P. Assimacopoulos: Exotoxins of Group A Streptococci 5: Stan Shulman, Robert R. Tanz, Michael Gerber: Streptococcal Pharyngitis 6: Elia Ayoub, Malak Kotb, Madelaine Cunningham: Rheumatic Fever Pathogenesis 7: Edward Kaplan, Milton Markowitz: Rheumatic Fever 8: Dennis Stevens, Bascom Anthony: Impetigo 9: Stig Holm: Post Streptococcal Glomerulonephritis 10: Dennis Stevens: Life Threatening Streptococcal Infections: bacteremia, streptococcal toxic shock syndrome, and necrotizing fasciitis 11: Vicor Nizet, Craig Rubens, Patricia Ferrieri: Group B Streptococcal Genetics and Pathogenesis 12: Carol Baker: Group B Streptococcal Infections 13: Alan Bisno, Jose Miltoy Gaviria: Group C & G Streptococcal 14: Judy Daly: The Non-Hemolytic Streptococci 15: Diana Martin: Laboratory Evaluation of Streptococci 16: Walter Wilson: Viridans and Fastidious Strep Infections 17: Larry J. Strausbaugh, Micheal Gilmore: Enterococcal Infections 18: Barry Gray: Streptococcus pneumoniae Infections 19: Mark C. Hertzberg: Streptococcus in dental disease 20: Vincent Fischetti: Protection against Group A Streptococcal Infection 21: Jim Dale: Type Specific, Multi-valent Group A Streptococcal M protein Vaccines 22: Mike Wessels, Dennis Kasper: Group B Streptococcal Vaccines 23: David Briles: Vaccine Strategies in Streptococcus pneumoniae.
Association between the abnormal expression of matrix‐degrading enzymes by human osteoarthritic chondrocytes and demethylation of specific CpG sites in the promoter regions (2005)

This study provides the first evidence that altered synthesis of cartilage-degrading enzymes by late-stage OA chondrocytes may have resulted from epigenetic changes in the methylation status of CpG sites in the promoter regions of these enzymes. These changes, which are clonally transmitted to daughter cells, may contribute to the development of OA.
Synthesis and Characterization of Alternating Copolymers of Fluorene and Oxadiazole (2002)

Alternating copolymers of 9,9-dioctylfluorene and oxadiazole have been prepared by the tetrazole route or the Suzuki coupling reaction. In the polymers the oxadiazole units were evenly dispersed in the main chain at every one, P(F1-alt-Ox), three, P(F3-alt-Ox), or four, P(F4-alt-Ox), fluorene units. Another copolymer with an asymmetric repeat unit structure, P(F3−Ox−F1−Ox) has also been prepared for comparison. In this study, the tetrazole route has been demonstrated to offer several advantages for preparing polyoxadiazole with well-defined structures compared to other oxadiazole ring formation reactions. These advantages include: clean and fast reactions, mild reaction conditions, high yields, and high molecular masses of product. The glass transition temperature of copolymers ranged from 98 to 150 °C, and the copolymers show high thermal stability with decomposition temperatures around 430 °C. The UV−vis absorption and photoluminescence properties of all the copolymers in solutions are similar to those of poly(9,9-dioctylfluorene). All copolymers fluoresce in the blue-light range with quantum yields of ∼70% in CH2Cl2 solution.
Assessment of the intrinsic urethral sphincter component function in postprostatectomy urinary incontinence (2002)

Postprostatectomy incontinence remains a disabling condition. Sphincter injury, detrusor instability, and decreased bladder compliance have been previously reported as major factors. The aim of this study was to evaluate the urethral sphincter intrinsic component, which may provide passive continence. A urodynamic evaluation was performed in 20 patients undergoing a radical retropubic prostatectomy in the preoperative period and 3 months after surgery. Patients with disabled urinary incontinence underwent a new urodynamic evaluation 6 months later. The urethral pressure profile was measured just before, then 10, 20, and 30 minutes after the injection of 0.5 mg/kg moxisylyte chlorhydrate, an alpha adrenergic blocker. Three different pressure components were defined in urethral sphincter capacity: baseline, adrenergic, and voluntary. A postoperative intrinsic urethral sphincter pressure component was found in 17 patients and its value was under 6 cm H(2)O in five cases of severe incontinence. No significant difference was observed for these patients on urethral profile components 6 months later. In contrast, in cases of significant intrinsic component value, no incontinence was observed in most patients. Passive continence after radical prostatectomy should be a matter of concern and may also explain paradoxical incontinence, despite high voluntary urethral pressure obtained after reeducation. A follow-up evaluation of the intrinsic sphincter component is suggested, by using an alpha receptor blockage test during urodynamic studies in the management of patients with postprostatectomy incontinence.
Clinical study of relative biological effectiveness for cervical carcinoma treated by 252Cf neutrons and assessed by histological tumour eradication (1990)

Clinical data of the University of Kentucky trial using californium (252Cf), or caesium (137Cs), are reviewed for dose-response based on the endpoint of tumour eradication estimated from hysterectomy specimens obtained 4-6 weeks after preoperative irradiation. These data are used to assess the relative biological effectiveness (RBE) for 252Cf neutrons compared with 137Cs gamma radiation. Tumours treated were of common stage but were of bulky or barrel shape suitable for "radiosurgical" therapy. Dose-response curves were constructed, and additional data from the literature used to analyse the curve shape. The photon dose-response curve is complex on a logarithmic plot, whereas the 252Cf neutron curve is exponential. This indicates that the RBE can be different depending on the number of implants, schedule and size of dose delivered per session. The RBE values were approximately 8.0 at low doses or for multiple implants but they may rise to approximately 16 at larger doses or for single 252Cf implants.