Closure of a nonhealing gastrocutaneous fistula using an endoscopic clip

Gastrocutaneous fistula after gastrostomy tube removal may persist for a prolonged period. We present a case of a 58-year-old woman with a GCF that had persisted for 5 months following the removal of an endoscopically-placed gastrostomy tube (PEG). Conservative therapy with anti-acid medications and administering motility agents was unsuccessful. For the closure of the GCF, the endoscopic metal clips were used to close the fistula.     

Rotator Cuff Tear Susceptibility Is Associated With Variants in Genes Involved in Tendon Extracellular Matrix Homeostasis

Rotator cuff tears (RCT) is a multifactorial disease with genetic factors contributing for the disease etiology. We hypothesized that genetic variants in genes involved in extracellular matrix (ECM) homeostasis may alter susceptibility to RCT. We evaluated 20 polymorphisms of genes involved in ECM homeostasis in 211 cases of full-thickness tears of the supraspinatus (N_females = 130; N_males = 81) and 567 age-matched controls (N_females = 317; N_males = 250). Multivariate logistic regressions were carried out with age, gender, genetic ancestry (based on the analysis of 61 biallelic short insertion/deletion polymorphisms), and common co-morbidities (diabetes, dyslipidemia, and smoking habits) as covariates. We observed that carriers of the rare allele of both studied variants of TGFB1, as well as their G/A (rs1800470/rs1800469) haplotype, were less susceptible to RCT (p < 0.05). In contrast, carriers of the G allele of MMP9 rs17576 (p = 0.014) or G/G haplotype (rs17576/rs17577; p < 0.001) had an increased risk for tendon tears. The presence of the T allele of MMP2 rs2285053 (p = 0.033), the T allele of MMP3 rs679620 (p = 0.024), and the TT-genotype of TIMP2 rs2277698 (p = 0.01) was associated with susceptibility to tears, especially in females. In males, the A allele of COL5A1 rs3196378 (p = 0.032) and the G allele of TGFBR1 rs1590 (p = 0.039) were independent risk factors for RCT. The C/T COL5A1 (rs3196378/rs11103544) haplotype was associated with a reduced risk of tears in males (p = 0.03). In conclusion, we identified the genetic variants associated with RCT susceptibility, thereby reinforcing the role of genes involved in the structure and homeostasis of the ECM of tendons in disease development. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:192–201, 2020     

Pathology of inherited manganese transporter deficiency

We followed a patient with manganese transporter deficiency due to homozygous SLC30A10 mutations from age 14 years until his death at age 38 years and present the first postmortem findings of this disorder. The basal ganglia showed neuronal loss, rhodanine‐positive deposits, astrocytosis, myelin loss, and spongiosis. SLC30A10 protein was reduced in residual basal ganglia neurons. Depigmentation of the substantia nigra and other brainstem nuclei was present. Manganese content of basal ganglia and liver was increased 16‐fold and 9‐fold, respectively. Our study provides a pathological foundation for further investigation of central nervous system toxicity secondary to deregulation of manganese metabolism. Ann Neurol 2014;75:608–612     

Failure of response to N5-methyltetrahydrofolate in combined folate and B12 deficiency

A patient with combined folate and B₁₂ deficiency due to tropical sprue failed to respond to the administration of N⁵-methyltetrahydrofolate when given by mouth or intravenously. After the injection of 1 μg of B₁₂ intravenously the patient became asymptomatic and laboratory tests returned to normal. Failure of response to N⁵-methyltetrahydrofolate in the presence of B₁₂ deficiency is evidence in favor of the “folate trap” hypothesis.     

Chemical Modifications of Transfer RNA Species. Desulfurization with Raney Nickel

A single, modified nucleoside in Escherichia coli tRNA, 6-(3-methyl-2-butenylamino)-2-methyl-thio-9-beta-D-ribofuranosylpurine, has been desulfurized with Raney nickel to afford its probable biosynthetic precursor. The limitations of the reaction at the nucleoside and tRNA levels and its lack of inhibition of the amino acid acceptor activity of tRNA are described.     

Exo1: a new chemical inhibitor of the exocytic pathway

A phenotypic screen was used to search for drug-like molecules that can interfere with specific steps in membrane traffic. 2-(4-Fluorobenzoylamino)-benzoic acid methyl ester (Exo1), identified in this screen, induces a rapid collapse of the Golgi to the endoplasmic reticulum, thus acutely inhibiting the traffic emanating from the endoplasmic reticulum. Like Brefeldin A (BFA), Exo1 induces the rapid release of ADP-ribosylation factor (ARF) 1 from Golgi membranes but has less effect on the organization of the trans-Golgi network. Our data indicate that Exo1 acts by a different mechanism from BFA. Unlike BFA, Exo1 does not induce the ADP-ribosylation of CtBP/Bars50 and does not interfere with the activity of guanine nucleotide exchange factors specific for Golgi-based ARFs. Thus, Exo1 allows the fatty acid exchange activity of Bars50 to be distinguished from ARF1 activity in the control of Golgi tubulation.     

THE CONDENSATION OF THE ADENYLATES OF THE AMINO ACIDS COMMON TO PROTEIN

Simultaneous formation of the adenylates of the 18 amino acids common to protein, followed by cocondensation, has yielded polymers containing all of those amino acids. The condensation occurred rapidly at room temperature above pH 7. The activated amino acids were reacted with thermally synthesized polyanhydro-alpha-amino acids to yield polymers of substantially increased size. The modified polyamino acids form micron-sized particles which demonstrate internal synthesis by growth and budding. These particles are stable over a wide range of pH.From thermal polyamino acids alone, answers have earlier been obtained, in principle, to questions of the primordial origin of enzymes, cellular structure, membranes, systematic anhydroamino acid sequences, and propagation of microsystems. Such a model is largely heterotrophic; the mixed adenylate condensation provides, in principle, a partial answer to the origin of syntheses of peptide bonds within protocellular structures.