Connective tissue growth factor. Friend or foe?

Connective tissue growth factor (CTGF) is a novel cysteine-rich, secreted peptide, which is implicated in human atherosclerosis and fibrotic disorders such as systemic scleroderma. CTGF is a member of the peptide family that includes serum-induced immediate early gene products, a v-src-induced peptide, and a putative proto-oncogene. The CTGF gene family is a modular protein and is conserved throughout evolution. CTGF mRNA has been found in the human, mouse, chicken, frog, and fly. The functions of the CTGF gene family include embryogenesis, wound healing, and regulation of extracellular matrix production. Human CTGF is undetectable in normal blood vessels but overexpressed in atherosclerotic lesions, suggesting an important role in atherogenesis.     

Applications of hysteresis switching in parameter adaptive control

The hysteresis switching algorithm of R.H. Middleton et al. (ibid., vol.33, no.1, p.50-8, Jan. 1988) is reexamined in a broader context. To demonstrate its utility, the algorithm is applied to various families of identifier-based parameterized controllers of both the direct and indirect control types. Application to the direct control type results in a model reference adaptive controller capable of stabilizing, without excitation, any SISO process which can be modeled by a minimum phase linear system whose transfer function has relative and McMillan degrees not exceeding prescribing integers m and n, respectively. It is shown that such processes can also be adaptively stabilized with indirect adaptive controllers and hysteresis switching. A simple numerical example involving a non-minimum-phase process model is used to illustrate how hysteresis switching might be applied to implicitly tuned parameterized controllers to realize an adaptive controller with capabilities which might prove very difficult, if not impossible, to achieve without hysteresis switching or some other form of discontinuous control     

Direct evidence for the deoxyribonuclease activity of the plant ribosome inactivating protein gelonin

Several plant ribotoxins, including gelonin, were reported to have additional weak nuclease activities on supercoiled DNA. The potential contribution of this activity to their cytotoxicity has not been given serious consideration due to concerns about contaminating nucleases in the protein preparations. We now report the degradation of single-stranded DNA by preparations of native plant gelonin and recombinant gelonin produced in E. coli. The DNase activity of both preparations is similarly modulated by zinc. An SDS-PAGE DNase assay identifies gelonin as the polypeptide responsible for deoxyribonuclease activity.     

Flecainide overdose: is cardiopulmonary support the treatment?

Flecainide toxicity can impair cardiac function and precipitate circulatory collapse, which in turn depresses clearance and redistribution of flecainide. Treatment directed at improving cardiac function is often ineffective in the presence of persistently increased flecainide levels. We report a novel approach to severe flecainide overdose using peripheral cardiopulmonary bypass support (CBS) to maintain perfusion of the liver, thereby allowing clearance of the drug. CBS was initiated to resuscitate a young woman who had ingested flecainide in a suicide attempt. The patient had an agonal rhythm, no effective blood pressure, and a flecainide level of 5.4 micrograms/mL (therapeutic range, .2 to 1.0 microgram/mL). During 10 hours of CBS, the flecainide level decreased to 1.4 micrograms/mL, a half-life of 6 hours. Effective cardiac rhythm and blood pressure returned. CBS successfully supported this patient until the flecainide level decreased as a result of redistribution and normal clearance mechanisms. Unfortunately, because of severe neurologic damage sustained at the time of overdose, the patient died 4 days after admission.