Fibroblast activation protein drives tumor metastasis via a protease-independent role in invadopodia stabilization.

During metastasis, tumor cells invade through the basement membrane and intravasate into blood vessels and then extravasate into distant organs to establish metastases. Here, we report a critical role of a transmembrane serine protease fibroblast activation protein (FAP) in tumor metastasis. Expression of FAP and TWIST1, a metastasis driver, is significantly correlated in several types of human carcinomas, and FAP is required for TWIST1-induced breast cancer metastasis to the lung.

Atomic-scale identification of nitrogen dopants in graphene on Ir(111) and Ru(0001).

Nitrogen (N) doped graphene materials have been synthesized using the sole precursor adenine on the Ir(111) and Ru(0001) surfaces. X-ray photoelectron spectroscopy and scanning tunneling microscopy (STM) have been used to characterize the obtained N-doped graphene materials. Several graphitic and pyridinic N dopants have been identified on the atomic scale by combining STM measurements and STM simulations based on density functional theory calculations.

Crescentic Osteotomy for Revision Hallux Interphalangeal Joint Arthrodesis.

Unlabelled: Treatment for rigid mallet toe deformity of the hallux has commonly consisted of arthrodesis of this interphalangeal joint. However, such procedure is not without complications resulting in operative revision. We report on a case of considerable deformity of the distal phalanx of the hallux following hallux interphalangeal joint arthrodesis that underwent revision using a unique crescentic osteotomy technique.

Suppression of tumor growth in mice by rationally designed pseudopeptide inhibitors of fibroblast activation protein and prolyl oligopeptidase.

Tumor microenvironments (TMEs) are composed of cancer cells, fibroblasts, extracellular matrix, microvessels, and endothelial cells. Two prolyl endopeptidases, fibroblast activation protein (FAP) and prolyl oligopeptidase (POP), are commonly overexpressed by epithelial-derived malignancies, with the specificity of FAP expression by cancer stromal fibroblasts suggesting FAP as a possible therapeutic target. Despite overexpression in most cancers and having a role in angiogenesis, inhibition of POP activity has received little attention as an approach to quench tumor growth.

Evaluation of Hallux Interphalangeal Joint Arthroplasty Compared With Nonoperative Treatment of Recalcitrant Hallux Ulceration.

Patients with chronic diabetes can develop plantar hallux ulcerations secondary to neuropathy, increased pressure, and deformity. The present retrospective study evaluated the efficacy of hallux interphalangeal joint (HIPJ) arthroplasty to address recalcitrant ulceration. Two groups of patients with diabetes were compared: a surgical group of 13 patients and a nonsurgical standard therapy group of 13 patients.

Genetic analysis of low BMI phenotype in the Utah Population Database.

The low body mass index (BMI) phenotype of less than 18.5 has been linked to medical and psychological morbidity as well as increased mortality risk. Although genetic factors have been shown to influence BMI across the entire BMI, the contribution of genetic factors to the low BMI phenotype is unclear.

Targeting inhibition of fibroblast activation protein-α and prolyl oligopeptidase activities on cells common to metastatic tumor microenvironments.

Fibroblast activation protein (FAP), a membrane prolyl-specific proteinase with both dipeptidase and endopeptidase activities, is overexpressed by reactive stromal fibroblasts during epithelial-derived cancer growth. FAP digests extracellular matrix as tissue is remodeled during cancer expansion and may also promote an immunotolerant tumor microenvironment. Recent studies suggest that nonspecific FAP inhibitors suppress human cancer xenografts in mouse models.

Executive function in eating disorders: the role of state anxiety.

Objective: We examined the influence of depression and anxiety on executive function in individuals with a DSM-IV diagnosis of anorexia nervosa-restricting type, anorexia nervosa-binge-eating/purging type, bulimia nervosa, or eating disorder not otherwise specified.

Method: We assessed 106 women after their inpatient treatment in an eating disorders program. All participants were nutritionally stable at the time of testing.

Evaluation and biomechanics of the first ray in the patient with limited motion.

Adequate first ray function is essential to healthy human gait. Controversies still exist about aspects of human structure and function and many newer answers and theories have been proposed by a new generation of experts. Examples include the sagittal plane facilitation, tissue stress, and preferred movement pathway theories.

Noncovalent interaction of alpha(2)-antiplasmin with fibrin(ogen): localization of alpha(2)-antiplasmin-binding sites.

Covalent incorporation (cross-linking) of plasmin inhibitor alpha(2)-antiplasmin (alpha(2)-AP) into fibrin clots increases their resistance to fibrinolysis. We hypothesized that alpha(2)-AP may also interact noncovalently with fibrin prior to its covalent cross-linking. To test this hypothesis, we studied binding of alpha(2)-AP to fibrin(ogen) and its fragments by an enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance.

Granular cell tumor of the toe: a case report.

Unlabelled: The authors present a case of a granular cell tumor of the second digit that was treated with a partial digit amputation. A 49-year-old male presented with an atypical hyperkeratotic lesion at the distal aspect of the second toe with adjacent dystrophy of the nail plate. Radiographs, magnetic resonance images, and, finally, ultrasound images were used to confirm the presence of an underlying mass, and biopsy confirmed the diagnosis of granular cell tumor.

Using substrate specificity of antiplasmin-cleaving enzyme for fibroblast activation protein inhibitor design.

Circulating antiplasmin-cleaving enzyme (APCE), a prolyl-specific serine proteinase, is essentially identical to membrane-inserted fibroblast activation protein (FAP) that is transiently expressed during epithelial-derived cancer growth. Human precursive alpha(2)-antiplasmin (Met-alpha(2)AP), the only known physiologic substrate for APCE, is cleaved N-terminally to Asn-alpha(2)AP that is rapidly cross-linked to fibrin and protects it from digestion by plasmin. Identifying a specific inhibitor of APCE/FAP continues to be intensely pursued.

Rate of inpatient weight restoration predicts outcome in anorexia nervosa.

Objective: To examine weight restoration parameters during inpatient treatment as predictors of outcome in anorexia nervosa (AN).

Method: Adolescent and adult females admitted for inpatient eating disorder treatment were recruited for an ongoing longitudinal study. This analysis examined several weight restoration parameters as predictors of clinical deterioration after discharge among participants with AN.

Attention-deficit hyperactivity symptoms and disorder in eating disorder inpatients.

Objective: The objective of this study was to determine the prevalence of attention-deficit hyperactivity disorder (ADHD) symptoms and a DSM-IV ADHD diagnosis in women admitted for treatment of an eating disorder.

Method: One hundred eighty-nine inpatient women with an eating disorder were interviewed using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) and ADHD interview from the Multi-international Psychiatric Interview (MINI).

Results: Twenty-one percent of the sample reported at least six current ADHD symptoms, but the estimated prevalence rate for a diagnosis of ADHD in this population was only 5.

Phase II trial of single agent Val-boroPro (Talabostat) inhibiting Fibroblast Activation Protein in patients with metastatic colorectal cancer.

Purpose: Fibroblast Activation Protein (FAP) is a tumor fibroblast protease that has been shown to potentiate colorectal cancer growth. The clinical impact of FAP inhibition was tested using Val-boroPro (Talabostat), the first clinical inhibitor of FAP enzymatic activity, in a phase II study of patients with metastatic colorectal cancer.

Methods: Patients with metastatic colorectal cancer who had previously received systemic chemotherapies were treated with single agent Val-boroPro 200 microg p.

The effect of a single nucleotide polymorphism on human alpha 2-antiplasmin activity.

The primary inhibitor of plasmin, alpha(2)-antiplasmin (alpha(2)AP), is secreted by the liver into plasma with Met as the amino-terminus. During circulation, Met-alpha(2)AP is cleaved by antiplasmin-cleaving enzyme (APCE), yielding Asn-alpha(2)AP, which is crosslinked into fibrin approximately 13 times faster than Met-alpha(2)AP. The Met-alpha(2)AP gene codes for either Arg or Trp as the sixth amino acid, with both polymorphic forms found in human plasma samples.

Effect of fibroblast activation protein and alpha2-antiplasmin cleaving enzyme on collagen types I, III, and IV.

The circulating enzyme, alpha2-antiplasmin cleaving enzyme (APCE), has very similar sequence homology and proteolytic specificity as fibroblast activation protein (FAP), a membrane-bound proteinase. FAP is expressed on activated fibroblasts associated with rapid tissue growth as in embryogenesis, wound healing, and epithelial-derived malignancies, but not in normal tissues. Its presence on stroma suggests that FAP functions to remodel extracellular matrix (ECM) during neoplastic growth.

Poststreptococcal reactive arthritis.

Acute rheumatic fever is a delayed inflammatory disease that follows streptococcal infection of the throat. Poststreptococcal reactive arthritis is a sterile arthritis associated with antecedent streptococcal infection in patients not fulfilling the Jones criteria for acute rheumatic fever. Poststreptococcal reactive arthritis has been reported to have lower-extremity predominance and, therefore, should be included in the differential diagnosis of patients with lower-extremity arthritis.

Antiplasmin-cleaving enzyme is a soluble form of fibroblast activation protein.

Circulating antiplasmin-cleaving enzyme (APCE) has a role in fibrinolysis and appears structurally similar to fibroblast activation protein (FAP), a cell-surface proteinase that promotes invasiveness of certain epithelial cancers. To explore this potential relationship, we performed comparative structure/function analyses of the 2 enzymes. APCE from human plasma and recombinant FAP (rFAP) exhibited identical pH optima of 7.

Neural network predictions of significant coronary artery stenosis in men.

Objective: A neural network system was designed to predict whether coronary arteriography on a given patient would reveal any occurrence of significant coronary stenosis (>50%), a degree of stenosis which often leads to coronary intervention.

Methodology: A dataset of 2004 records from male cardiology patients was derived from a national cardiac catheterization database. The catheterizations selected for analysis from the database were first-time and elective, and they were precipitated by chest pain.

Alpha2-antiplasmin: potential therapeutic roles in fibrin survival and removal.

Alpha2-antiplasmin (alpha2AP) is the primary inhibitor of plasmin, a proteinase that digests fibrin, the main component of blood clots. Two forms of alpha2AP circulate in human plasma: a 464-residue protein with methionine as the amino-terminus (Met-alpha2AP) and an N-terminally-shortened 452-residue form with asparagine as the amino-terminus (Asn-alpha2AP). Human plasma alpha2AP concentration is 1 micro M and consists of approximately 30% Met-alpha2AP and approximately 70% Asn-alpha2AP.

A novel plasma proteinase potentiates alpha2-antiplasmin inhibition of fibrin digestion.

Human alpha2-antiplasmin (alpha2AP), also known as alpha2-plasmin inhibitor, is the major inhibitor of the proteolytic enzyme plasmin that digests fibrin. There are 2 N-terminal forms of alpha2AP that circulate in human plasma: a 464-residue protein with Met as the N-terminus, Met-alpha2AP, and a 452-residue version with Asn as the N-terminus, Asn-alpha2AP. We have discovered and purified a proteinase from human plasma that cleaves the Pro12-Asn13 bond of Met-alpha2AP to yield Asn-alpha2AP and have named it antiplasmin-cleaving enzyme (APCE).

Using therapeutic community principles to improve the functioning of a high care psychiatric ward in the UK.

The effects of interventions within a high-care psychiatric ward, based upon the principles of a therapeutic community, were evaluated. Interventions included an enhanced physical environment, improved communication, clear rules and aims, and improved safety procedures. A Ward Atmosphere Scale, an Attitude Scale, and interviews with staff indicated improvements in ward atmosphere and staff attitudes.