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Biomedical subjects

J Wickham

Publications and source records attributed to J Wickham.

11 recordsLinked to original sources
PubMed2004

The histone deacetylase inhibitor MS-275 induces caspase-dependent apoptosis in B-cell chronic lymphocytic leukemia cells.

MS-275 is a histone deacetylase (HDAC) inhibitor that has been reported to mediate its cytotoxic effect through generation of reactive oxygen species (ROS) in proliferating hematopoietic cell lines. We examined efficacy of MS-275 in nonproliferating chronic lymphocytic leukemia (CLL) cells from patients. In these cells, MS-275 demonstrated an in vitro LC(50) that was one log lower than for normal mononuclear cells. Following MS-275 treatment, histones H3 and H4 showed increased acetylation and HDAC enzymatic activity was reduced. Caspase-8, -9, and -3 were activated, and caspase substrates PARP and BID were cleaved. Additionally, FLICE-inhibitory protein (FLIP) was downmodulated following MS-275 incubation. MS-275 treatment caused detectable ROS generation after 15 h of incubation, which was blocked by the caspase inhibitor Z-VAD-fmk. Overexpression of Bcl-2 protein protected against MS-275-induced apoptosis. These data demonstrate that MS-275 is a promising therapy for the treatment of CLL, but that in contrast to previous reports, ROS generation does not precede commitment to apoptosis. Similar to many other therapeutic targets, MS-275-mediated apoptosis is reduced by overexpression of Bcl-2, justifying strategies to combine HDAC inhibitors with Bcl-2 antagonists.

Apoptosis↗
PubMed2003

Anatomical and possible clinical relationships between the calcaneofibular ligament and peroneus brevis--a pilot study.

The authors have observed in their clinical practice patients presenting with chronic retromalleolar pain following lateral ankle injuries. It has been hypothesized that persistent retromalleolar pain following a supination sprain may be due to peroneus brevis (PB) tendon tears (Boruta et al. 1990). The aims of this study were to investigate whether an anatomical relationship exists between the calcaneofibular ligament (CFL) and PB, and if so, the significance of this relationship in the positions of supination sprain and talar tilt test. Seven out of eight cadaveric ankles demonstrated fibrous connecting tissue between the tendon of PB and CFL. Four of the eight ankles demonstrated PB tendon abnormalities. The presence of connecting tissue between CFL and PB suggests an anatomical basis for concomitant damage to the PB tendon with a supination sprain, thus supporting the hypothesis that there may be an anatomical basis for persistent retromalleolar pain subsequent to injury to the lateral ankle complex.

Ankle Injuries↗
PubMed2000

Shape control of CdSe nanocrystals

Nanometre-size inorganic dots, tubes and wires exhibit a wide range of electrical and optical properties that depend sensitively on both size and shape, and are of both fundamental and technological interest. In contrast to the syntheses of zero-dimensional systems, existing preparations of one-dimensional systems often yield networks of tubes or rods which are difficult to separate. And, in the case of optically active II-VI and III-V semiconductors, the resulting rod diameters are too large to exhibit quantum confinement effects. Thus, except for some metal nanocrystals, there are no methods of preparation that yield soluble and monodisperse particles that are quantum-confined in two of their dimensions. For semiconductors, a benchmark preparation is the growth of nearly spherical II-VI and III-V nanocrystals by injection of precursor molecules into a hot surfactant. Here we demonstrate that control of the growth kinetics of the II-VI semiconductor cadmium selenide can be used to vary the shapes of the resulting particles from a nearly spherical morphology to a rod-like one, with aspect ratios as large as ten to one. This method should be useful, not only for testing theories of quantum confinement, but also for obtaining particles with spectroscopic properties that could prove advantageous in biological labelling experiments and as chromophores in light-emitting diodes.

Journal Article↗
PubMed1999

A balance of signaling by Rho family small GTPases RhoA, Rac1 and Cdc42 coordinates cytoskeletal morphology but not cell survival.

Rho family GTPases are known to be involved in cytoskeletal reorganization. We examined the possibility that these functions may be dictated by a balance of Rho family GTPase signaling. Using transient viral expression of RhoA, Rac1, Cdc42 and their mutants, as well as C3 exoenzyme, we altered cytoskeletal organization under normal growth conditions. Overexpression of wild-type or constitutively active forms of the Rho family GTPases led to their respective activation phenotypes. Overexpression of dominant negative forms of given Rho family GTPases led to a phenotype consistent with activation of the other Rho family GTPase. Treatment with C. difficile toxin A, that inactivates all Rho family GTPases, led to the transient appearance of a variety of activation phenotypes. Previously, we reported that inactivation of Rho led to induction of apoptosis, implying that Rho may play an important role in cell survival signaling. This signaling, however, is not affected by expression of any forms of Rac1 or Cdc42, and only inactivation of Rho led to induction of apoptosis. Rho family GTPases appear to coordinate cytoskeletal organization by a balance of signaling, while cell survival is regulated by a distinct Rho-mediated signaling pathway.

Animals↗
PubMed1991

Minimally invasive therapy.

A rapid change is taking place in the development of less invasive surgical and radiological techniques. The consequences of these changes may have considerable implications for clinical work patterns and institutional design in the next decade. Surgeons, radiologists and health economists must be prepared to recognise and react rapidly to these radical shifts in technology which are aimed at the reduction of patient morbidity and mortality.

Ambulatory Surgical Procedures↗
PubMed1989

Current management of urinary calculi.

Open surgery for the removal of renal and ureteric calculi has been rendered almost obsolete in the last eight years. The development of the extracorporeal lithotripter and the pulsed dye laser has permitted many patients to have their stones treated without anaesthesia on an outpatient basis.

Adult↗
PubMedDate not supplied

Tachyarrhythmia therapy utilizing electrical stimulation: a review.

The review is structured in such a way as to fall naturally into four main sections. These are as follows: clinical overview of the common mechanisms leading to the generation of tachyarrhythmias; commonly used sensing techniques and algorithms for the detection of tachyarrhythmias; electrical stimulation algorithms used to terminate many of the rhythms; existing implantable devices and a brief look at the future. The clinical overview introduces the reader unfamiliar with tachyarrhythmias to such mechanisms as sinus tachycardia, supraventricular tachycardias (SVTs), ventricular tachycardia, 'torsade de pointes', and ventricular fibrillation. SVT includes paroxysmal SVT, atrial flutter, atrial tachycardia and junctional tachycardia (enhanced automaticity). Also there is a brief introduction to alternative therapies (drugs, surgery etc.) The sensing techniques section covers input signal processing to enable the R wave to be adequately detected; while the tachycardia detection algorithms section discusses such areas as simple rate detect, rate of change of rate detect, stability of rate, the so-called probability density function technique and some other more complex detection algorithms. The section on electrical stimulation algorithms used for tachycardia therapy discusses burst pacing techniques, special cases such as automatically decrementing bursts and automatically incrementing bursts, defibrillation shock therapy (since fibrillation is a form of tachyarrhythmia) and several other more complex algorithms. The review finishes up with a discussion of current implantable antitachy pacemakers and defibrillators. There is also a speculative look at the future to enable the reader to obtain a full picture.

Algorithms↗