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Objectives: To explore the aetiological, clinical and radiological profiles of patients with LETM presenting to this tertiary care hospital in North India., Patients and Methods: All eligible LETM patients presenting to our hospital between April 2015 and Jan 2016 were prospectively studied. A total of 37 patients were included and after thorough history, examination, relevant laboratory and radiological investigation, were profiled according to the various aetiologies of LETM., Results: Our study included 37 patients (62% males and 38% females). Most patients were young (21-30 years). Main aetiologies of LETMp were NMO (8), inflammatory (9), idiopathic (6), NMOSD (4), Vitamin B 12 deficiency (4) and others (6). Most patients (62%) had acute onset of symptoms except NMOSD and B 12 deficient patients who presented subacutely too. NMO group was most disabled (poor Rankin and MRC assessments) at presentation; prognostically no (87%) or minimal improvement (13%) at discharge was seen in this group compared to other aetiologies. Forty point five percent patients had thoracic sensory complaints. CSF (pleocytosis 62%) and raised protein (81%) and brain abnormalities on MRI were seen in 11% patients. Bladder and optic nerve involvement (75.7% and 35% patients respectively). Seventy five percent NMO and 67% probable inflammatory aetiology patients also had B 12 deficiency., Conclusion: This study concludes that LETMp has varied aetiologies with NMO having more disability and poorer outcomes. Thoracic cord segment is most commonly involved. Vitamin B 12 deficiency may predispose patients to inflammatory LETM including NMO syndromes., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Many proteins display complex folding kinetics, which represent multiple parallel folding pathways emanating from multiple unfolded forms and converging to the unique native form. The small protein thioredoxin from Escherichia coli is one such protein. The effect of the chaperonin GroEL on modulating the complex energy landscape that separates the unfolded ensemble from the native state of thioredoxin has been studied. It is shown that while the fluorescence change accompanying folding occurs in five kinetic phases in the absence of GroEL, only the two slowest kinetic phases are discernible in the presence of saturating concentrations of GroEL. This result is shown to be consistent with only one out of several available folding routes being operational in the presence of GroEL. It is shown that native protein, which forms via fast as well as slow routes in the absence of GroEL, forms only via a slow route in its presence. The effect of GroEL on the folding of thioredoxin is shown to be the consequence of it binding differentially to the many folding-competent forms. While some of these forms can continue folding when bound to GroEL, others cannot. All molecules are then drawn into the operational folding route by the law of mass action. This observation indicates a new role for GroEL, which is to bias the energy landscape of a folding polypeptide towards fewer available pathways. It is suggested that such channeling might be a mechanism to avoid possible aggregation-prone routes available to a refolding polypeptide in vivo., (Copyright 2001 Academic Press.)

Despite extensive structural and kinetic studies, the mechanism by which the Escherichia coli chaperonin GroEL assists protein folding has remained somewhat elusive. It appears that GroEL might play an active role in facilitating folding, in addition to its role in restricting protein aggregation by secluding folding intermediates. We have investigated the kinetic mechanism of GroEL-mediated refolding of the small protein barstar. GroEL accelerates the observed fast (millisecond) refolding rate, but it does not affect the slow refolding kinetics. A thermodynamic coupling mechanism, in which the concentration of exchange-competent states is increased by the law of mass action, can explain the enhancement of the fast refolding rates. It is not necessary to invoke a catalytic role for GroEL, whereby either the intrinsic refolding rate of a productive folding transition or the unfolding rate of a kinetically trapped off-pathway intermediate is increased by the chaperonin., (Copyright 2000 Academic Press.)