Activated Src kinase promotes cell cannibalism in Drosophila.

Src family kinases (SFKs) are evolutionarily conserved proteins acting downstream of receptors and regulating cellular processes including proliferation, adhesion, and migration. Elevated SFK expression and activity correlate with progression of a variety of cancers. Here, using the Drosophila melanogaster border cells as a model, we report that localized activation of a Src kinase promotes an unusual behavior: engulfment of one cell by another.

Treatment of superficial venous insufficiency in a large patient cohort with retrograde administration of ultrasound-guided polidocanol endovenous microfoam versus endovenous laser ablation.

Objective: To evaluate outcomes among symptomatic patients with superficial chronic venous insufficiency treated with retrograde ultrasound-guided polidocanol endovenous microfoam 1% (PEM) or endovenous laser ablation (EVLA).

Methods: This study is a retrospective chart review from a single vein center between October 2013 and June 2019. Procedures were performed on 1070 patients with Clinical, Etiologic, Anatomic, and Pathophysiologic class 2 to 6 disease and symptomatic superficial venous reflux of the great saphenous vein or anterior accessory saphenous vein.

Automated virtual reality exposure therapy for spider phobia vs. in-vivo one-session treatment: A randomized non-inferiority trial.

This study compared the efficacy of a technician-assisted single-session virtual reality exposure therapy (VRET) for the treatment of spider phobia featuring low-cost consumer-available hardware and novel automated software to gold-standard in-vivo one-session treatment (OST), using a parallel group randomized non-inferiority design. Method Participants (N = 100) were randomized to VRET and OST arms. Assessors blinded to treatment allocation evaluated participants at pre- and post-treatment as well follow-up (3 and 12 months) using a behavioral approach test (BAT) and self-rated fear of spider, anxiety, depression and quality-of-life scales.

Retrograde administration of ultrasound-guided endovenous microfoam chemical ablation for the treatment of superficial venous insufficiency.

Objective: This study measured patient outcomes among symptomatic patients with superficial chronic venous insufficiency who were treated with retrograde ultrasound-guided polidocanol microfoam 1% in a community setting.

Methods: Between March 2015 and June 2017, 250 symptomatic patients with C2-C6 chronic venous insufficiency received polidocanol microfoam 1% and were followed for 16 ± 7 months. Sixteen of the 250 patients (6.

New atropisomeric amino alcohol ligands for enantioselective addition of diethylzinc to aldehydes.

Efficient synthesis of several new atropisomeric amino alcohols having 1-phenyl-1H-pyrrole skeleton are reported. Steric arrangements of the products were confirmed by a single-crystal X-ray measurement. The consequences of the size of the N-substituents on enantioinduction were examined by employing the enantioselective catalytic addition of diethylzinc to a series of substituted benzaldehydes (yields 91-97%, up to 85% enantiomeric excess).

Glucopyranosylidene-spiro-iminothiazolidinone, a new bicyclic ring system: synthesis, derivatization, and evaluation for inhibition of glycogen phosphorylase by enzyme kinetic and crystallographic methods.

The reaction of thiourea with O-perbenzoylated C-(1-bromo-1-deoxy-β-D-glucopyranosyl)formamide gave the new anomeric spirocycle 1R-1,5-anhydro-D-glucitol-spiro-[1,5]-2-imino-1,3-thiazolidin-4-one. Acylation and sulfonylation with the corresponding acyl chlorides (RCOCl or RSO₂Cl where R=tBu, Ph, 4-Me-C₆H₄, 1- and 2-naphthyl) produced the corresponding 2-acylimino- and 2-sulfonylimino-thiazolidinones, respectively. Alkylation by MeI, allyl-bromide and BnBr produced mixtures of the respective N-alkylimino- and N,N'-dialkyl-imino-thiazolidinones, while reactions with 1,2-dibromoethane and 1,3-dibromopropane furnished spirocyclic 5,6-dihydro-imidazo[2,1-b]thiazolidin-3-one and 6,7-dihydro-5H-thiazolidino[3,2-a]pyrimidin-3-one, respectively.

Multiple defects in type III collagen synthesis are associated with the pathogenesis of abdominal aortic aneurysms.

Confluent skin fibroblast cultures were prepared from 40 patients diagnosed with and surgically treated for an abdominal aortic aneurysm. An analysis of secreted type I and type III collagen in the media of these fibroblast preparations revealed reduced secretion of type III collagen from six patients. DNA sequence analysis of the entire coding domain of the pro alpha 1 (III) collagen mRNA in skin fibroblast RNA from these six patients revealed a C to T substitution at nucleotide 607 in one of the probands that would result in the replacement of a leucine residue with phenylalanine in the second position of the first tripeptide repeat in the triple-helical domain of type III collagen.

Extensive alternate exon usage at the 5' end of the sheep tropoelastin gene.

Several overlapping cDNA clones were isolated from a lambda gt10 cDNA library constructed using poly A+ RNA from neonatal sheep lung. DNA sequence analysis of these cDNA recombinants revealed the complete derived amino acid sequence of sheep tropoelastin. A comparison of DNA sequences from individual sheep tropoelastin cDNA also confirmed the presence of several tropoelastin mRNA isoforms in neonatal lung tissue.

Increases in type III collagen gene expression and protein synthesis in patients with inguinal hernias.

Objective: The aim of this study was to determine if alterations in fibrillar collagen synthesis were associated with the development of inguinal hernias.

Summary Background Data: Previous work has suggested that alterations in connective tissue accumulation may play a functional role in the development of inguinal hernias. In particular, several investigators have suggested that alterations in collagen synthesis, causally related to connective disorders such as osteogenesis imperfecta, may also be responsible for the inguinal herniation that is markedly increased in such patients.

Quantitation of tropoelastin mRNA and assessment of alternative splicing in human skin fibroblasts by reverse transcriptase-polymerase chain reaction.

We have developed a reverse transcriptase-polymerase chain reaction (RT-PCR) assay for the quantitative measurement of levels of tropoelastin mRNA in total RNA preparations from skin fibroblasts. This method facilitates the reproducible detection of low abundance tropoelastin mRNA in the range of 10-1000 copies per cell. The procedure is based on a competitive RT-PCR assay where a tropoelastin cDNA-derived internal RNA standard is cotranscribed and coamplified together with the sample derived-endogenous target mRNA.

Regulation of collagen gene expression in keloids and hypertrophic scars.

The synthesis of type I and III collagens in cultured skin fibroblasts from normal skin, normal scar, hypertrophic scar, and keloids was examined. The ratio of type I/III collagen was significantly elevated in keloids compared to that in the other groups. When mRNA steady-state levels coding for alpha 1(I) procollagen were determined, it was apparent that this increase in the type I/III collagen ratio in keloids was paralleled by a specific increase in alpha 1(I) procollagen mRNA.

A restriction fragment length polymorphism results in a nonconservative amino acid substitution encoded within the first exon of the human lysyl oxidase gene.

A cDNA covering most of the coding sequence for human lysyl oxidase was used to screen, by Southern blot analysis, genomic DNA from circulating lymphocytes obtained from unrelated, apparently normal individuals. A heritable restriction fragment length polymorphism (RFLP) within a PstI restriction site was detected in 36% of individuals screened (a total of 72 chromosomes were analyzed). The major allele was represented as a 1.

The complete derived amino acid sequence of human lysyl oxidase and assignment of the gene to chromosome 5 (extensive sequence homology with the murine ras recision gene).

Lysyl oxidase catalyzes the oxidation of lysine residues to alpha-aminoadipic-delta-semialdehyde. This is the first step in the covalent cross-linking of collagen and tropoelastin and results in the formation of insoluble collagen and elastic fibers in the extracellular matrix. We have characterized the complete nucleotide sequence of human lysyl oxidase (EC 1.

Abnormalities in the biosynthesis of type III procollagen in cultured skin fibroblasts from two patients with multiple aneurysms.

We examined the synthesis of collagenous proteins by cultured skin fibroblasts taken from 14 patients with an abdominal aortic aneurysm and either an aneurysm at a second site (8 patients) or a first order relative with an abdominal aortic aneurysm (6 patients). Fibroblasts were labeled with [3H] proline and, following pepsin digestion of media proteins, the ratio of type I/III collagen was examined by denaturing polyacrylamide gel electrophoresis (SDS-PAGE). With the exception of two patients, the ratio of type I/III collagen in the media of fibroblasts from aneurysm patients was similar to control values (6 controls).

Elements of the rat tropoelastin gene associated with alternative splicing.

Multiple isoforms of tropoelastin, the soluble precursor of elastin, are the products of translation of splice-variant mRNAs derived from the single-copy tropoelastin gene. Previous data had demonstrated DNA sequence heterogeneity in three domains of rat tropoelastin mRNA, indicating alternative splicing of several exons of the rat tropoelastin gene. Rat tropoelastin genomic clones encompassing the sites of alternative splicing were isolated and sequenced.

Changes in aortic levels of tropoelastin mRNA following treatment of rats with the antihypertensive drugs captopril and hydralazine.

This manuscript describes changes in the steady state levels of aortic tropoelastin mRNA in spontaneously hypertensive rats (SHR) and normotensive controls (WKY) following treatment with two antihypertensive drugs. Three-week-old WKY and SHR rats were treated with hydralazine (15 mg/kg/day) or captopril (25 mg/kg/day). Tail artery blood pressure was monitored twice weekly.

The substitution of arginine for glycine 85 of the alpha 1(I) procollagen chain results in mild osteogenesis imperfecta. The mutation provides direct evidence for three discrete domains of cooperative melting of intact type I collagen.

We report a case of mild osteogenesis imperfecta in a 56-year-old male undergoing aortic valve replacement surgery. The primary defect in this patient was the substitution of arginine for glycine 85 in one of the two chains of alpha 1(I) procollagen. The thermal stability of the type I collagen synthesized by the patient's cultured skin fibroblasts was examined by enzymatic digestion.

Alternative splicing of rat tropoelastin mRNA is tissue-specific and developmentally regulated.

Sequence analysis of cDNA clones coding for rat tropoelastin previously has identified two variants that potentially corresponded to alternatively spliced tropoelastin mRNAs (Pierce et al., 1990). We have now used S1 nuclease protection analysis of total RNA from aorta, skin and lungs of 10-day and 6-week old rats to localize all sites of alternative splicing in the tropoelastin mRNA and to examine tissue-specific and developmental regulation of the use of these sites.

Desmoplasia in benign and malignant breast disease is characterized by alterations in level of mRNAs coding for types I and III procollagen.

Desmoplasia, the formation of excessive connective tissue surrounding some neoplasms, is a well documented, but incompletely understood phenomenon. To characterize the fibrotic response in benign breast conditions and malignancy, we examined the steady state levels of mRNA coding for types I and III procollagen in mild fibrocystic changes, in fibroadenoma, and in infiltrating ductal carcinoma. The results indicate that in mild fibrocystic change there is a relative increase in type III procollagen mRNA.

Mammalian tropoelastin: multiple domains of the protein define an evolutionarily divergent amino acid sequence.

We have recently derived the complete amino acid sequence of rat tropoelastin from a series of overlapping cDNA clones. Comparison of this protein sequence to bovine and human tropoelastin has revealed significant differences in the rates of evolutionary divergence of the various domains of tropoelastin. The overall rate of divergence of the hydrophobic domains of tropoelastin was twice as fast as the cross-link domains of the protein.