This paper examines the development and termination of nebacumab (Centoxin®), a human IgM monoclonal antibody (mAb) drug frequently cited as one of the notable failures of the early biopharmaceutical industry. The non-approval of Centoxin in the United States in 1992 generated major concerns at the time about the future viability ...

Monoclonal antibodies (mAbs) are known to cause hypersensitivity reactions (HSRs). The reactions pose a significant challenge to investigators, regulators, and health providers. Because HSRs cannot be predicted through the pharmacological basis of a therapy, clinical data are often relied upon to detect the reactions. Unfortunately, clinical studies are often unable ...

Humanized monoclonal antibodies (mAbs) are the fastest growing class of biological therapeutics that are being developed for various medical indications, and more than 30 mAbs are already approved and in the market place. Antibody-dependent cell-mediated cytotoxicity (ADCC) is an important biological function attributed to the mechanism of action of several ...

Antibodies are among the most powerful tools in biological and biomedical research and are presently the fastest growing category of new bio-pharmaceutics. The most common format of antibody applied for therapeutic, diagnostic and analytical purposes is the IgG format. For medical applications, recombinant IgGs are made in cultured mammalian cells ...

There are currently ~25 recombinant full-length IgGs (rIgGs) in the market that have been approved by regulatory agencies as biotherapeutics to treat various human diseases. Most of these are based on IgG1k framework and are either chimeric, humanized or human antibodies manufactured using either Chinese hamster ovary (CHO) cells or ...

Antibody-drug conjugates (ADCs) with biotin as a model cargo tethered to IgG1 mAbs via different linkers and conjugation methods were prepared and tested for thermostability and ability to bind target antigen and Fc receptor. Most conjugates demonstrated decreased thermostability relative to unconjugated antibody, based on DSC, with carbohydrate and amine ...

In therapeutic or diagnostic antibody discovery, affinity maturation is frequently required to optimize binding properties. In some cases, achieving very high affinity is challenging using the display-based optimization technologies. Here we present an approach that begins with the creation and clonal, quantitative analysis of soluble Fab libraries with complete diversification ...

Multispecificity is not a well-understood property of some antibodies. Different functions have been attributed to multispecific natural antibodies, commonly associated with the neutralization and clearance of antigens. Much less is known about the role of antibodies like these, based on their idiotypic connectivity. B7Y33 is a chimeric IgG1 version of ...

We have previously reported evidence that repetitions of letters, colors, sizes, and common motion paths are more rapidly detected when they are presented unilaterally (i.e., both in the same visual field) versus bilaterally (one element in each visual field; Butcher and Cavanagh (Attention, Perception, & Psychophysics 70:714-724, 2008). Here, we ...

Torque teno sus virus (TTSuV) is responsible for the infection of pig herds around the world. The aim of this study was to analyse the presence of natural infection by both species of TTSuV in suckling piglets from major pig-producing regions of Brazil. Faecal samples (n = 135) from 1 to 3-week-old ...

BACKGROUND: Patient-specific virtual reality simulation (PSVR) is a new technological advancement that allows practice of upcoming real operations and complements the established role of VR simulation as a generic training tool. This review describes current developments in PSVR and draws parallels with other high-stake industries, such as aviation, military, and ...

Abstract Methotrexate (MTX) at a dose of ≥1 g/m(2) remains the most efficient treatment against primary central nervous system lymphoma (PCNSL), and is the most widely used drug in prospective clinical trials. MTX is a folate analogue that inhibits dihydrofolate reductase, thereby blocking de novo purine synthesis. MTX as well ...

BACKGROUND: Primary biliary cirrhosis (PBC) is a chronic, progressive liver disease with elevated serum lipids. It remains unclear if hyperlipidemia increases the risk for atherosclerosis in PBC patients. Metabolic syndrome (MS) promotes the development of atherosclerotic cardiovascular disease due to abdominal obesity and insulin resistance. AIMS: The aim of this ...

Modern thrombophilia testing fails to identify any underlying prothrombotic tendency in a significant number of patients presenting with objectively confirmed venous thromboemboembolism (VTE). This observation has led to a search for other novel inherited or acquired human thrombophilias. Although a number of putative mechanisms have been described, the evidence behind ...

There is little information known about the energy requirements of cats in temperature climates. Energy requirement of domestic short-haired cats was determined using three groups of mixed gender - old kept outside (approximately 9.9 years of age; 4.8 kg; n = 9), young kept outside (approximately 3.1 years of age; 3.9 kg; n = 8) or young kept ...

Meiotic pachytene checkpoints monitor the failure of homologous recombination and synapsis to ensure faithful chromosome segregation during gamete formation. To date, the molecular basis of the mammalian pachytene checkpoints has remained largely unknown. We here report that mouse HORMAD1 is required for a meiotic prophase checkpoint that eliminates asynaptic oocytes. ...

Twenty-two 5-benzylidenethiazolidine-2,4-dione derivatives (TZDs) were synthesized and evaluated for their potency on adipogenesis of 3T3-L1 adipocytes by measuring the expression of adiponectin protein. Among them, compared to rosiglitazone, 3V was found to upregulate the adiponectin protein expression and downregulate the secretion of leptin protein in 3T3-L1 adipocytes at a respective ...

Seedling roots display not only gravitropism but also hydrotropism, and the two tropisms interfere with one another. In Arabidopsis (Arabidopsis thaliana) roots, amyloplasts in columella cells are rapidly degraded during the hydrotropic response. Degradation of amyloplasts involved in gravisensing enhances the hydrotropic response by reducing the gravitropic response. However, the ...

INTRODUCTION AND HYPOTHESIS: The purpose of this study was to evaluate the intra- and postoperative urologic complications and management in patients with cervical or endometrial cancer treated with laparoscopic radical hysterectomy and lymphadenectomy. METHODS: We retrospectively reviewed the medical records of 146 patients with cervical or endometrial cancer who underwent ...

INTRODUCTION: Disc degeneration and re-herniation after nucleotomy procedures are common problems. Simultaneous application of hyaluronic acid (HA)-based matrix has been proposed to limit disc degeneration. This, however, is hampered by loss of the substituted matrix out of the disc. Hence, in situ polymerization of the injected matrix with ultraviolet light ...

A simple and efficient ambient ionization method based on paper spray combined with tandem mass spectrometry allows rapid detection and quantitation of various contaminants (clenbuterol, melamine, plasticizer and sudan red) in various foodstuffs (e.g., meat, milk, sports drinks and chili powder).

The growth dynamics of bacterial populations are usually represented by the classical S-shaped profiles composed of lag, exponential and stationary growth phases. Although exceptions to this classical behavior occur, they are normally produced under non-standard conditions such as supply of two carbohydrates as sole carbon source. However, we here report ...

We examined the joint trajectories of violent victimization and marijuana use from emerging adulthood to the early thirties and their health consequences in the early thirties among urban African American and Puerto Rican men. Data were collected from a community sample of young men (N = 340) when they were 19, 24, ...

Couples who have children are increasingly likely to have lived together without being married at some point in their relationship. Some couples begin their unions with cohabitation and marry before first conception, some marry during pregnancy or directly after the first birth, while others remain unmarried 3 years after the ...

Patients with lung cancer have numerous and varying needs spanning across the cancer trajectory; however, only limited research has focused specifically on the pre-diagnosis phase. A multicentre cross-sectional survey was conducted to explore the experience of lung cancer patients during the pre-diagnosis phase. High levels of anxiety were reported by ...

Sodium pumps (EC 3.6.3.9, Na(+)-ATPase), which mediate excretion of Na(+) from the cell, play a crucial role in Na(+) homeostasis in eukaryotic cells. The objective of this study is to understand the Na(+) efflux system in a marine red alga. We identified a novel sodium pump gene, PyKPA2, from the ...

Sickle cell disease (SCD) is an inherited chronic haemolytic anaemia whose clinical manifestations arise from the tendency of the haemoglobin to polymerize and deform red blood cells into the characteristic sickle shape due to a single nucleotide change in the β-globin. Vascular occlusion of small and large vessels can lead ...

The purpose of this study is to report two cases of idiopathic uveitis with secondary epiretinal membrane (ERM) formation in order to describe histologic and immunohistochemical features that may help distinguish uveitic from idiopathic ERMs. The study utilized a clinical case series and histopathological and immunohistochemical findings. There was no ...

This study reports on the C-terminal fragment of the 11S proteasome activator complex (PA28 or Reg alpha), a novel ovarian-specific biomarker of early and late stages of ovarian cancer (OVC) relapse, in patient biopsies after chemotherapy. A total of 179 tissue samples were analyzed: 8 stage I, 55 stage III-IV, ...

This study reviews empirical findings on two debated issues related to the phenomenon of impulse control disorders (ICD) in patients with Parkinson's disease (PD) treated with dopamine agonists: the role of "premorbid" or "baseline" personality traits and the role of cognitive status. A review of both these issues may help ...

This study determined whether N-acetylcysteine (NAC) could affect intestinal redox status, proinflammatory cytokines, epidermal growth factor (EGF), EGF receptor (EGFR), Toll-like receptor-4 (TLR4), and aquaporin-8 in a lipopolysaccharide (LPS)-challenged piglet model. Eighteen piglets (35-day-old) were randomly allocated into one of the three treatments (control, LPS and NAC). The control and ...

Porcine reproductive and respiratory syndrome virus (PRRSV), Haemophilus parasuis and Pseudorabies become a widespread problem causing great economic losses associated with reproductive disturbance, respiratory diseases, neonatal mortality, fibrinous polyserositis, meningitis and arthritis in the pig industry. The important candidate genes are assumed to play crucial roles in host defense against ...

Aim:  Targeted newborn hearing screening for infants in neonatal intensive care units (NICUs) may be considered when resources preclude universal newborn hearing screening (UNHS). However, process outcomes have not been compared between stand-alone NICU hearing screening programs and NICU screening within a full UNHS program. Methods:  Comparison of two consecutive ...

OBJECTIVES: Dopamine neurotransmission is a critical factor for executive function, which is controlled by the prefrontal cortex in humans. Although the contribution of genetic factors to the regulation of brain dopaminergic activity is widely acknowledged, identification of a genotype-phenotype association has not yet been clearly established. In this study, we ...

Tris(2,4,6-trimethoxyphenyl) phosphonium acetyl (TMPP-Ac) was previously introduced to improve the mass spectrometric sequence analysis of peptides by fixing a permanent charge at the N-termini. However, peptides containing arginine residues did not fragment efficiently after TMPP-Ac modification. In this work, we combine charge derivatization with photodissociation. The fragmentation of TMPP-derivatized peptides ...

Nonsymbiotic hemoglobins (nsHbs) are involved in a variety of cellular processes in plants. Previous studies indicate that nsHb expression improves plant tolerance during waterlogging and hypoxia. In the present work, the nsHb class-1 coding sequence was cloned from Malus hupehensis Rehd. var. pinyiensis Jiang and subsequently named MhGLB1. The results ...

Vascular endothelial growth factor (VEGF) inhibitors have significantly improved outcomes in patients with advanced renal cell carcinoma (RCC). Multiple VEGF inhibiting orally administered tyrosine kinase inhibitors (TKIs) have been approved including sunitinib, sorafenib, pazopanib and most recently, axitinib. One VEGF inhibiting monoclonal antibody, bevacizumab, is approved in combination with interferon. ...

Aim:  This retrospective study compares the overall survival (OS) of Multiple Myeloma (MM) patients following treatment at a New Zealand hospital over a period in which novel therapies were available but restricted, almost exclusively, to thalidomide as a second line therapy. Methods:  Clinical, laboratory and OS data were collected on ...

We report strong photoluminescence in an ultra-small surface oxidized SiC quantum dot-sodium dodecyl sulfonate crosslinked network. The peak emission wavelength is tunable spanning a wide blue-violet spectral region showing clear quantum confinement effects. The photoluminescence decay exhibits triple recombination dynamics with an average lifetime of 13.65 ns.

A field experiment was conducted at the Research Farm of CCS HAU, Hisar to study the dissipation and decontamination behavior of bifenthrin on tomato crop following the application of 25 g a.i ha(-1) (T(1)) and 50 g a.i ha(-1) (T(2)). Samples were collected periodically on the sampling days after applications. Residues were ...

Summary.  The incidence of haemophilic arthropathy in multiple joints decreased due to treatment with clotting factor. Nowadays patients are enabled to live a rather normal life, resulting in more (sports) trauma-induced arthropathy in isolated joints like the ankle. As surgical treatment options, fusion of the tibiotalar joint and total ankle ...

Tris[3,5-bis(trifluoromethyl)phenyl]borane (, BArF(18)), has been synthesised on a practical scale for the first time. According to the Gutmann-Beckett method it is a more powerful Lewis acid than B(C(6)F(5))(3). It forms a 'frustrated Lewis pair' with 2,2,6,6-tetramethylpiperidine which cleaves H(2) to form a salt containing the novel anion [μ-H(BArF(18))(2)](-).

Due to the high morbidity and mortality of colorectal cancer (CRC), this study aims to determine the joint association of RE-1-silencing transcription factor (REST) and nuclear factor-κB 1 (NFKB1) genes with CRC in a population-based study. A well-matched case-control study including 390 controls and 388 patients with CRC was enrolled ...

PURPOSE: Complex percutaneous interventions often require high radiation doses likely to produce skin radiation injuries. We assessed the methodology used to select patients with potential skin injuries in cardiac procedures and in need of clinical follow-up. We evaluated peak skin dose and clinical follow-up in a case of radiodermatitis produced ...

Quantitative reverse transcription polymerase chain reaction (qRT-PCR) is a specific and sensitive technique for quantifying gene expression. To analyze qRT-PCR data accurately, suitable reference genes that show consistent expression patterns across different tissues and experimental conditions should be selected. The objective of this study was to obtain the most stable ...

This paper includes a nontechnical description of methods for calculating effect sizes in intellectual and developmental disability studies. Different hypothetical studies are used to illustrate how null hypothesis significance testing (NHST) and effect size findings can result in quite different outcomes and therefore conflicting results. Whereas NHST uses probability levels ...

PURPOSE: To predict the success of labor induction by sonographic cervical measurements, maternal/obstetrical factors, and the Bishop's score. METHODS: Between February 2008 and February 2010, 190 consecutive pregnant women underwent clinical examination to assess the Bishop's score and transvaginal sonographic cervical measurements (cervical length, fetal head stage, and cervical dilatation) ...

BACKGROUNDS: The main complication of trapeziometacarpal replacement is trapezial cup loosening due to an imperfect positioning of the trapezial component. This problem is quite similar to those related to other arthroplasties. Hip surgery was progressed toward computer-assisted surgery (CAS) for the improvement of acetabular cup positioning. In this study, we ...

The objective of this was to establish the effects of red spectrum of light (650 nm, treated n = 12) and normal spectrum of light (450 nm control = 12) on GnRH-I mRNA expression, amplitude and frequency of luteinizing hormone (LH), and egg production from 72-82 weeks of age in white leghorn hens. Birds exposed to red ...

BACKGROUND: Alpha-fetoprotein (AFP) has been used as a diagnostic biomarker for hepatocellular carcinoma (HCC), but its prognostic significance is not well defined. This study was performed to classify the prognostic significance of AFP status in HCC patients after transarterial chemoembolization (TACE). METHODS: Four hundred forty-one HCC patients from a prospective ...