Anticoagulation Management for Veno-Venous ECMO in COVID-19 Patients: Argatroban as Rescue Therapy in Heparin-Associated Thrombocytopenia.

Extracorporeal membrane oxygenation (ECMO) has been widely used as a life support technique in COVID-19 acute respiratory distress syndrome (ARDS). The use of anticoagulation during ECMO support remains a topic of debate. The primary aim of this study is to demonstrate the safety and efficacy of using argatroban as an anticoagulant instead of heparin in patients with heparin-associated thrombocytopenia.

Landmark detection in 2D bioimages for geometric morphometrics: a multi-resolution tree-based approach.

The detection of anatomical landmarks in bioimages is a necessary but tedious step for geometric morphometrics studies in many research domains. We propose variants of a multi-resolution tree-based approach to speed-up the detection of landmarks in bioimages. We extensively evaluate our method variants on three different datasets (cephalometric, zebrafish, and drosophila images).

Effects of microgravity simulation on zebrafish transcriptomes and bone physiology-exposure starting at 5 days post fertilization.

Physiological modifications in near weightlessness, as experienced by astronauts during space flight, have been the subject of numerous studies. Various animal models have been used on space missions or in microgravity simulation on ground to understand the effects of gravity on living animals. Here, we used the zebrafish larvae as a model to study the effect of microgravity simulation on bone formation and whole genome gene expression.

Zebrafish Bone and General Physiology Are Differently Affected by Hormones or Changes in Gravity.

Teleost fish such as zebrafish (Danio rerio) are increasingly used for physiological, genetic and developmental studies. Our understanding of the physiological consequences of altered gravity in an entire organism is still incomplete. We used altered gravity and drug treatment experiments to evaluate their effects specifically on bone formation and more generally on whole genome gene expression.

Patent portfolios after myriad, how to fit in those new genes?

The recent US Supreme Court decision in Association for Molecular Pathology v. Myriad Genetics, Inc. clarified what is considered patentable subject matter.

Carboxy-terminal processing of the urokinase receptor: implications for substrate recognition and glycosylphosphatidylinositol anchor addition.

Proteins linked to cell membranes by a glycosylphosphatidylinositol (GPI) anchor must first undergo cleavage by a putative transamidase between the omega and omega + 1 positions within a proposed small amino acid (SAD) domain in the carboxy terminus of the nascent polypeptide. The requirements for such processing, defined in an engineered placental alkaline phosphatase construct (miniPLAP), suggest the SAD domain functions as an autonomous unit within the context of an otherwise permissive carboxy-terminal sequence with only certain amino acids tolerated at the omega, omega + 1, and omega + 2 positions. To test whether this hypothesis could be generalized, we engineered a chimeric molecule containing the extracellular domain of miniPLAP and the carboxy-terminal portion of the urokinase receptor (MP/uPAR) into which various amino acid substitutions were introduced.

Unesterified long chain fatty acids inhibit the binding of single chain urokinase to the urokinase receptor.

The interaction of single chain urokinase with its receptor accelerates plasminogen activator activity on cell surfaces and induces intracellular signalling in several cell types. To date, no physiologic inhibitor of this binding has been identified. We report that the binding of scuPA to its cellular receptor is inhibited by long chain fatty acids such as oleic acid (C18, delta 9) at physiological plasma concentrations.

ATP-dependent regulation of sodium-calcium exchange in Chinese hamster ovary cells transfected with the bovine cardiac sodium-calcium exchanger.

Chinese hamster ovary cells expressing the bovine cardiac Na/Ca exchanger were treated with ouabain to increase [Na+]i and stimulate Ca2+ influx by Na/Ca exchange. Depletion of cellular ATP inhibited 45Ca uptake by 40% or more and reduced the half-maximal Na+ concentration for inhibition of 45Ca uptake from 90 to 55 mM. ATP depletion also reduced the rate of rise in [Ca2+]i when [Na+]o was reduced and inhibited the decline in [Ca2+]i when high [Na+]o was restored.

PMSLIC's new coverage for retired physicians: we do all count.

The Pennsylvania Medical Society Liability Insurance Company now offers medical liability insurance coverage for retired member physicians who write prescriptions for themselves or their immediate families. Though the coverage was just approved by the Insurance Department in August of this year, it was in the making for more than 10 years. This is a background.

Stable expression of the cardiac sodium-calcium exchanger in CHO cells.

A line of Chinese hamster ovary (CHO) cells called CK1.4 was produced by transfection with the gene for the bovine cardiac Na(+)-Ca2+ exchanger. CK1.

Cloning and expression of the bovine cardiac sodium-calcium exchanger.

Two clones (p17 and p13), each containing the complete coding sequence for the bovine cardiac Na+/Ca2+ exchanger, were obtained from a lambda gt10 cDNA library by screening with cDNA probes from the canine exchanger. The coding sequence of clone p17 was 92 and 98% identical to the canine cDNA at the nucleotide and amino acid levels, respectively. Nine of the 21 amino acid differences between the two exchangers were found within the 32-amino acid signal sequence.

The effect of lowered extracellular Na+ concentration on ultraviolet light-induced relaxation of vasoconstricted rabbit isolated thoracic aorta.

The effect of lowering extracellular ion concentration on ultraviolet (UV) light-induced photorelaxation of norepinephrine(NE)-constricted rabbit isolated thoracic aorta was investigated. The magnitude of the photorelaxation response (similar to acetylcholine-induced, but not nitroprusside-induced, relaxation) progressively declined, in the absence of an effect on NE-induced vasoconstriction, as the total extracellular ion concentration was progressively reduced. This diminution in the photorelaxation response was duplicated by isosmotic lowering of the extracellular concentration of Na+, but not other ions, from 145 to 25 mM and was not restored by the replenishment of the Na+ deficiency by equimolar amounts of mannitol or Li+.

Angiotensin II stimulation of protein synthesis and cell growth in chick heart cells.

The octapeptide [Ile5]angiotensin II (ANG II), which is the principal circulating hormone of the renin-angiotensin system, could modulate or mediate cardiac hypertrophy via indirect effects, through increases in total peripheral vascular resistance, or by direct effects on cardiac cells, which result in increased protein synthesis and cell growth. In this study we determined whether ANG II stimulated protein synthesis and cell growth in cultures of embryonic chick myocytes. After 3 h of exposure to ANG II, there were significant increases in total cellular protein at 120, 144, and 168 h and in the relative rate of protein synthesis at 120 and 144 h.

Renin-angiotensin system involvement in pressure-overload cardiac hypertrophy in rats.

We have recently shown that the octapeptide angiotensin II is a potent stimulus of protein synthesis and growth in cultured cardiomyocytes. The present study was performed to determine if the renin-angiotensin system was involved in regulating cardiac cell growth in vivo. The pressure-overload cardiac hypertrophy model that develops in abdominal aorta-constricted rats was studied.

[Sar1]angiotensin II receptor-mediated stimulation of protein synthesis in chick heart cells.

Cardiac hypertrophy is a process that occurs in response to various mechanical or hormonal stimuli. Stimulation of the renin-angiotensin system is involved in the process of cardiac hypertrophy through mechanisms related to increased peripheral vascular resistance and increased cardiac afterload. In this study we determined whether [Sar1]angiotensin II (ANG II) directly stimulated protein synthesis and cell growth in embryonic chick myocytes in cell culture.

Fetal expression of renin, angiotensinogen, and atriopeptin genes in chick heart.

The renin-angiotensin and atriopeptin systems play important roles in the regulation of volume and fluid homeostasis. The two systems have opposing physiologic actions in a number of tissues. Experiments were performed to determine whether there were differences in the developmental expression of the genes for renin, angiotensinogen, and atriopeptin.

Angiotensin II receptor-mediated stimulation of cytosolic-free calcium and inositol phosphates in chick myocytes.

We have described previously positive inotropy and increased levels of inositol-l-phosphate as in vitro responses to angiotensin II in cardiac tissue. In this study, changes in cardiac myocyte-free cytosolic calcium stimulated by angiotensin II were monitored with the fluorescent calcium indicator dye Fura-2. There was an initial peak transient increase followed by a sustained increase in cytosolic-free calcium in response to angiotensin II (10(-9)-10(-6) M).

Characterization of avian angiotensin II cardiac receptors: coupling to mechanical activity and phosphoinositide metabolism.

We have characterized the avian angiotensin II (AII) cardiac receptor and provide data that this receptor couples to both mechanical activity and phospholipid metabolism in the avian heart. In 10-day-old chicks, 125I-AII bound to a high affinity site (Kd = 10 nmol) and a low affinity site (Kd = 79.4 nmol) with estimated binding capacities of 531 and 1330 fmol/mg protein, respectively.

Effects of chronic treatment with verapamil on adrenoceptor-mediated contraction of rabbit aorta.

Rabbits received twice-a-day doses of verapamil for 8 days and, on day 9 they were sacrificed in order to test contractile responses of the aorta in vitro. Isolated rings of aorta received graded doses of KCl, norepinephrine and norepinephrine along with either phentolamine, phenoxybenzamine or additional (acute) verapamil. Treated rings (those from animals that received verapamil chronically) developed significantly less tension (E) in response to depolarizing doses of KCl, but the degree of developed tension was restored and, in fact, enhanced when the aortic tissue was tested after cold storage 24 hr later (day 10).

Measurement of thermodynamic parameters for norepinephrine contraction of isolated rabbit thoracic aorta.

The thermodynamic quantities of change in free energy (delta G degree'), change in enthalpy (delta H degree') and change in entropy (delta S degree') were determined for the interaction of norepinephrine with the alpha-1 adrenoceptor of vascular smooth muscle. Specifically, a standard isolated rabbit thoracic-aorta preparation was used to examine the effect of temperature on norepinephrine-induced isometric tension development. Dissociation constants (KA) for norepinephrine were determined at several temperatures over the range 25-40 degrees C from equiactive concentrations obtained before (A) and after (A') partial irreversible receptor blockade by phenoxybenzamine, plotted as 1/A against 1/A' (KA = (slope-1)/intercept).