Identification of an oncogenic form of the thrombopoietin receptor MPL using retrovirus-mediated gene transfer

Thrombopoietin and its receptor (MPL) are important regulators of megakaryopoiesis. We have identified an activating mutation of MPL using a combination of a retrovirus-mediated gene transfer and polymerase chain reaction-driven random mutagenesis. This point mutation causes a single amino acid substitution from Ser498 to Asn498 in the transmembrane region and abrogates factor-dependency of all interleukin-3-dependent cell lines tested. Murine interleukin-3- dependent Ba/F3 cells expressing the mutated but not the normal form of MPL were tumorigenic when transduced into syngeneic mice. Analysis of intracellular signaling pathways indicated that the mutant MPL protein constitutively activated two distinct signaling pathways, SHC-Raf-MAPK and JAK2-STAT3/STAT5.     

Elevated soluble intercellular adhesion molecule-1 levels in obesity: relationship to insulin resistance and tumor necrosis factor-alpha system activity.

Intercellular adhesion molecule-1 (ICAM-1) is 1 of the possible factors linking obesity and diabetes with cardiovascular disease, however, the mechanism of the increase in ICAM-1 concentration in obesity remains unclear. Therefore, the aim of the present study was to assess plasma soluble ICAM-1 (sICAM-1) levels in obese subjects with normal glucose tolerance and to evaluate whether those levels may be related to insulin resistance and tumor necrosis factor-alpha (TNFalpha) system activity. The study was performed in 8 lean and 15 obese subjects. Anthropometric and biochemical parameters were measured, and insulin sensitivity was evaluated using the euglycemic hyperinsulinemic clamp technique (insulin infusion, 50 mU x kg(-1) x h(-1)). Obese subjects were markedly more hyperinsulinemic and insulin resistant and had higher plasma soluble TNF receptor 2 (sTNFR2) and sICAM-1 levels. sICAM-1 was related positively to body mass index (BMI), waist-to-hip ratio (WHR), percent of body fat, glycated hemoglobin (HbA(1c)), plasma insulin and triglycerides (TG), TNFalpha, and sTNFR2 and negatively to insulin sensitivity. Multiple regression analysis showed that only sTNFR2 and insulin sensitivity were independent predictors of sICAM-1 concentrations and were responsible for 66% of sICAM-1 variability. We conclude that an increase in plasma sICAM-1 concentration in obesity is related to TNFalpha system activation and insulin resistance.     

Hazards of non coherent light sources as determined by the framework of IEC TR-60825-9

An overview is provided of the scope and application of IEC TR 60825-9 in determination of hazards of non coherent optical radiation sources. Specific areas reviewed in detail include those relating to hazards of ultraviolet radiation, retinal thermal hazard and blue light photochemical hazard. The effect of spectral temperature on relative risk relating to retinal thermal hazard and blue light photochemical hazard are outlined. Assessment of risk factors of these hazards was determined using a range of measurement devices including spectral radiometer, broad band power meter and a locally developed device for determination of pulse profile of pulsed light sources.     

Recurrent Spontaneous Paresthesia in the Upper Limb Could Be Due to Migraine: A Case Series

Transient neurologic dysfunction is a characteristic feature of migraine. About 20% of migraineurs may experience various symptoms in the absence of any headache at one time or another. Visual auras are the most common auras of migraine, and migraine is considered as the most common cause of transient vision loss in young patients. Sensory auras are the second most common migrainous auras. However, the literature is silent for isolated sensory aura as a migraine equivalent. Herein we report 14 patients with recurrent episodic paresthesia in the limbs and other body parts. All patients fulfilled the diagnostic criteria of “typical aura without headache” of ICHD‐3β. All patients were subjected to various investigations to rule out secondary causes. Ten patients received antimigraine drugs and all showed a positive response to therapy. Recurrent spontaneous paresthesia is quite common in the general population and many patients remain undiagnosed. We speculate that a subset of patients might be related to migrainous sensory auras.     

Erectile Impotence in Chronic Alcoholics

Erectile impotence is a common complaint in alcoholics, but its mechanism is unknown. We have studied nocturnal penile erection in 13 alcoholics who complained of impotence. Seven had normal erections and their impotence was therefore psychogenic. Six were found to have diminished or absent nocturnal erections. Plasma concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were elevated in this latter group, with the exception of one patient who had only raised FSH. They also had more evidence of neurological damage than the other seven alcoholics, and two had evidence of damage to the parasympathetic nervous system. Investigation of erection during sleep in alcoholic patients with impotence may be useful in differentiating clinically between patients with psychogenic causes and patients with organic causes of impotence.