GPA

Predicament of classification: Multisystem small vessel vasculitis with cresentic Glomerulonephritis

Published on: 9th April, 2018

OCLC Number/Unique Identifier: 7666350132

The patient is a 28-year old Caucasian man with six month history of arthralgia and crampy abdominal pain who presented with acute dyspnea and cough for 6 months associated with migratory polyarthralgias involving his knees, ankles, wrists, and shoulders.
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Mesoscopic irreversible thermodynamics of morphological evolution kinetics of helical conformation in bioproteins ‘DNA’ under the isothermal isobaric conditions

Published on: 11th March, 2020

OCLC Number/Unique Identifier: 8570215259

The morphological evolution kinetics and instabilities of alpha helical peptide 3.613, which involves large amount of stored torsional elastic deformation energy (3-40 eV/molecule), is formulated by the variational method based on the connection between the rates of internal entropy production and the changes in the global Gibbs free energy, assuming that one has isobaric irreversible processes under the isothermal conditions. The present mesoscopic nonequilibrium thermodynamic approach relies on the fact that the global Gibbs free energy of helical conformation involves not only the bulk Gibbs free energy of the amino-acid back bone structure but also the interfacial Gibbs free energy of the enclosing cylindrical shell or the cage associated with the side-wall molecular branches, and their interactions with the immediate surroundings. The proposed variational analysis applied directly on the proposed macro-model has furnished a nonlinear integral equation in terms of the normalized and scaled internal and external variables. This allows us to track down the motion of the total pitch height of the alpha polypeptide along the well-defined trajectories in the displacement-time space, dictated not only by the initial configuration of the helix but also through the gradients of the global Gibbs free energy of the strained helical conformation as the main driving force. In the negative manifold, there is a well-defined region below the dynamic instability regime, in which the helical conformation can evolve towards the nonequilibrium stationary states by expanding, or contracting, depending upon whether the interfacial free energy and/or the applied stress system are below or above the well-defined thresholds level dictated by the initial pitch height. The highest life time may be realized along that trajectory, which follows up the threshold level of the interfacial specific Gibbs free energy, which is gs = -315 erg/cm2. In the upper region of the negative manifold, the helical conformations are driven by the very large applied uniaxial tension or the negative pressure induced by the thermal expansion, in the range of p > 1GPa and/or the strong negative interfacial free energies [3-4 pH] or their combinations, they show strong kinematic instabilities, which can cause not only the accelerated unfolding phenomenon but also cause large extensions that end up with the catastrophic decimations by ruptures and fragmentations. In the positive manifold, the aging behavior of the polypeptide follows up a S-shape path having rather speedy aging behavior compared to the negative manifold, which is separated from by a well-defined boundary, which represents the isochoric path having longest relaxation times, which can be achieved with great stability. Finally, one could attempt to estimate the upper limit of the relaxation time of aging for the modern hominin, from samples of exceptional preservations, relying on the present nonequilibrium theory as well as on the very limited knowledge on the post-mortem DNA and the present pitch heights of the modern hominin, which is found to be about 25,840 yrs, with a life expectation of 451,800 yrs. These figures are very close to those calculated for Neanderthals (SH), which are found to be 31,820 yrs and 499,100 yrs, respectively.
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Granulomatosis with polyangiitis (GPA) in a 76-year old woman presenting with pulmonary nodule and accelerating acute kidney injury

Published on: 20th January, 2020

OCLC Number/Unique Identifier: 8516756417

Granulomatosis with polyangiitis (GPA), a form of ANCA-associated vasculitis (AAV), is a rare disease with an often-occult presentation. It is more common in 4th and 5th decades of life but can be seen in all ages. This case report details a 76-year-old female presenting with abdominal pain, generalized weakness, and malaise, who was found to have pulmonary nodules on chest imaging. Biopsy of the lung nodule showed organizing pneumonia. Initially, antibiotics were used to treat the patient. However, she developed acute renal failure a few days after presentation and found to have positive serum C-ANCA as well as elevated ANCA-PR3 serologies. A subsequent kidney biopsy demonstrated pauci-immune necrotizing and crescentic glomerulonephritis that was consistent with GPA and the patient was started immediately on combination immunosuppressive therapy, plasmapheresis, and hemodialysis. GPA’s clinical and radiological presentation can mimic other common conditions such as pneumonia, malignancy, bacterial sinusitis, pulmonary tuberculosis, sarcoidosis, and urinary tract infection. Because of this, a high level of suspicion is required for early diagnosis and treatment to alter the high mortality rate in this disease entity. All forms of ANCA-associated vasculitis (AAV) should be in the differential diagnosis for all patients presenting with multiorgan system involvement particularly in individuals with pulmonary and renal manifesations.
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