Nongenomic estrogen action regulates tyrosine phosphatase activity and tuberin stability

Estrogen action and tuberin function has been suggested to play a crucial role in the proliferation of lung smooth muscle-like cells and/or myofibroblasts in pulmonary lymphangioleiomyomatosis (LAM). Tuberin is a tumor suppressor phosphoprotein, which also regulates fluid phase endocytosis. Its activity, turnover and complex association with hamartin depends on its phosphorylation status. We have recently reported that nongenomic estrogen action regulates the phosphorylation status of several cytoplasmic proteins. Herein, we demonstrate that estrogen increases tyrosine phosphatase activity, which can be abrogated by antiestrogen ICI 182780 and tyrosine phosphatase inhibitor bpV(phen), but not by the protein synthesis inhibitor cyclohexamide. Furthermore, we show that estrogen transiently enhances the turnover of tuberin, which follows an inverse pattern to that observed for tyrosine phosphatase and endocytosis activity. We showed that tuberin phosphorylation protects it from degradation and induces its accumulation in female human lung fibroblasts and myofibroblasts. Our results suggest that nongenomic estrogen action induces tyrosine phosphatase activity that regulates stability of tyrosine phosphorylated proteins, including tuberin, which may play a crucial role in cellular specific functions such as endocytosis.     

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.     

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.     

Two‐faced haemophagocytic lymphohistiocytosis: comparative review of two cases of adult haemophagocytic lymphohistiocytosis

Haemophagocytic lymphohistiocytosis (HLH) is a rare but potentially fatal disease of children and adults. Cytokine dysfunction, uncontrolled accumulation of activated T‐cells and histiocytes, and the inability to terminate the immune response lead to the clinical manifestations of extreme inflammation and end‐organ damage. HLH is notoriously underreported because of its ability to mimic many other common diseases. Here, we outline two cases of HLH, one primary and the other secondary, to highlight some of the differences and to discuss therapeutic principles and emerging concepts.