Generation of a novel fully human non-superagonistic anti-CD28 antibody with efficient and safe T-cell co-stimulation properties.

Antibody-based therapeutics represent an important class of biopharmaceuticals in cancer immunotherapy. CD3 bispecific T-cell engagers activate cytotoxic T-cells and have shown remarkable clinical outcomes against several hematological malignancies. The absence of a costimulatory signal through CD28 typically leads to insufficient T-cell activation and early exhaustion.

Neutral sphingomyelinase mediates the co-morbidity trias of alcohol abuse, major depression and bone defects.

Mental disorders are highly comorbid and occur together with physical diseases, which are often considered to arise from separate pathogenic pathways. We observed in alcohol-dependent patients increased serum activity of neutral sphingomyelinase. A genetic association analysis in 456,693 volunteers found associations of haplotypes of SMPD3 coding for NSM-2 (NSM) with alcohol consumption, but also with affective state, and bone mineralisation.

A DNA-Encoded Chemical Library Based on Peptide Macrocycles.

The synthesis and characterization of a novel DNA-encoded library of macrocyclic peptide derivatives are described; the macrocycles are based on three sets of proteinogenic and non-proteinogenic amino acid building blocks and featuring the use of copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) reaction for ring closure. The library (termed YO-DEL) which contains 1 254 838 compounds, was encoded with DNA in single-stranded format and was screened against target proteins of interest using affinity capture procedures and photocrosslinking. YO-DEL selections yielded specific binders against serum albumins, carbonic anhydrases and NKp46, a marker of activated Natural Killer cells.

Matrix metalloproteinases and tissue inhibitors of metalloproteinases in patients with different types of scars and keloids.

Background: Hypertrophic scars and keloids are fibroproliferative skin disorders characterised by progressive deposition of collagen. Our study is designed to investigate the expression and concentration of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in different types of scars and keloids.

Methods: Total RNA from 19 proliferative hypertrophic scar samples of patients with extended burns (total body surface area (TBSA): 21+/-12%), 18 mature hypertrophic scar samples from patients after elective surgery, 14 keloid samples and 18 normotrophic scar samples was, respectively, extracted, and then mRNA was isolated.

Effect of tissue inhibitors of metalloproteinases and matrix metalloproteinases on capsular formation around smooth and textured silicone gel implants.

Background: Capsular contracture is one of the most distressing complications after cosmetic breast augmentation. Evidence suggests that matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) may play a key role in the onset or progression of several fibrotic disorders. In this study we used quantitative reverse-transcription PCR methodology to profile the expression of TIMP-1, TIMP-2, MMP-2, and MMP-9 in the tissue of patients with capsular contracture after breast augmentation with smooth and textured silicone breast implants.

Expression of matrix metalloproteinases and their inhibitors in cords and nodules of patients with Dupuytren's disease.

Introduction: Dupuytren's disease is a fibroproliferative disorder characterized by thickening of the palmar fascia. Several studies indicate that MMPs and TIMPs may play a key role in the onset or progression of Dupuytren's disease and related disorders. In this study, we used a quantitative reverse-transcription PCR methodology to profile the expression of TIMP1, TIMP2, MMP2, and MMP9 in nodule and cord tissue from patients with Dupuytren's disease and compared this with normal palmar fascia taken at carpal tunnel release.

Lipofibromatous hamartoma of the median nerve in patients with macrodactyly: diagnosis and treatment of a rare disease causing carpal tunnel syndrome.

Lipofibromatous hamartoma is a very rare benign peripheral nerve tumour. It is mostly encountered in the proximal extremities of young adults, involving the median nerve in the majority of cases. We present two patients with macrodactyly and carpal tunnel syndrome caused by lipofibromatous hamartoma of the median nerve and discuss diagnosis and treatment of the disease.