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.     

Role of copper in mitochondrial iron metabolism

Heme synthesis by copper-deficient cells was investigated to elucidate the nature of the defect in intracellular iron metabolism. Iron uptake from transferrin by copper-deficient reticulocytes was 52% of normal, and the rate of heme synthesis was 33% of normal. Hepatic mitochondria isolated from copper-deficient animals were deficient in cytochrome oxidase activity and failed to synthesize heme from ferric iron (Fe III) and protoporphyrin at the normal rate. The rate of heme synthesis correlated with the cytochrome oxidase activity. Heme synthesis from Fe(III) and protoporphyrin by normal mitochondria was enhanced by succinate and inhibited by malonate, antimycin A, azide, and cyanide. It is proposed that an intact electron transport system is required for the reduction of Fe(III), thereby providing a pool of ferrous iron (Fe II) for protoheme and heme a synthesis.     

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.     

Microanatomical study of testis in juvenile ostrich (Struthio camelus)

The majority of investigations on the testis, as the main organ of male reproductive system, have been performed in mammalian species, with few studies on bird species. Thus, the structure of the ostrich testis remains largely unknown. The aim of this study was to investigate the microanatomical characteristics of the testis in five juvenile ostriches. A stereological study was performed according to the Delesse principle. The mean volume fraction of the seminiferous tubules was 0.569, and the mean volume of the seminiferous tubules in an average testis was 1.04 cm³. The Paraffin-embedded sections were stained with hematoxylin and eosin, Masson’s trichrome, Alcian blue, and periodic acid–Schiff stains. Histological studies revealed that the spermatogonial stem cells and Sertoli cells were localized inside the seminiferous tubules, close to the basement membrane. Inside the tubules a few meiotic cells up to the spermatozoa stage were located in a centripetal manner. Outside the tubules, one to three layers of euchromatic peritubular myoid cells were present, surrounded by loose interstitial connective tissue. A thick tunica albuginea contained many myoid cells and some rete ducts, with the latter extending from the hilus to the free surface of the testis. Straight seminiferous tubules were distributed in the lateral surfaces and hilar portions of the capsule but were rare in the free surface. These capsular rete ducts may participate in testicular fluid transit from the distal tubules through the capsule.     

Higher Dietary Calcium Intakes Are Associated With Reduced Risks of Fractures,Cardiovascular Events,and Mortality: A Prospective Cohort Study of Older Men and Women

The aim of this population‐based, prospective cohort study was to investigate long‐term associations between dietary calcium intake and fractures, non‐fatal cardiovascular disease (CVD), and death from all causes. Participants were from the Melbourne Collaborative Cohort Study, which was established in 1990 to 1994. A total of 41,514 men and women (～99% aged 40 to 69 years at baseline) were followed up for a mean (SD) of 12 (1.5) years. Primary outcome measures were time to death from all causes (n = 2855), CVD‐related deaths (n = 557), cerebrovascular disease‐related deaths (n = 139), incident non‐fatal CVD (n = 1827), incident stroke events (n = 537), and incident fractures (n = 788). A total of 12,097 participants (aged ≥50 years) were eligible for fracture analysis and 34,468 for non‐fatal CVD and mortality analyses. Mortality was ascertained by record linkage to registries. Fractures and CVD were ascertained from interview ～13 years after baseline. Quartiles of baseline energy‐adjusted calcium intake from food were estimated using a food‐frequency questionnaire. Hazard ratios (HR) and odds ratios (OR) were calculated for quartiles of dietary calcium intake. Highest and lowest quartiles of energy‐adjusted dietary calcium intakes represented unadjusted means (SD) of 1348 (316) mg/d and 473 (91) mg/d, respectively. Overall, there were 788 (10.3%) incident fractures, 1827 (9.0%) incident CVD, and 2855 people (8.6%) died. Comparing the highest with the lowest quartile of calcium intake, for all‐cause mortality, the HR was 0.86 (95% confidence interval [CI] 0.76–0.98, p_trend = 0.01); for non‐fatal CVD and stroke, the OR was 0.84 (95% CI 0.70–0.99, p_trend = 0.04) and 0.69 (95% CI 0.51–0.93, p_trend = 0.02), respectively; and the OR for fracture was 0.70 (95% CI 0.54–0.92, p_trend = 0.004). In summary, for older men and women, calcium intakes of up to 1348 (316) mg/d from food were associated with decreased risks for fracture, non‐fatal CVD, stroke, and all‐cause mortality. © 2015 American Society for Bone and Mineral Research.     

Storage of platelet concentrates using ion exchange resin charged with dibasic phosphate.

Platelet concentrates were prepared at twice the normal concentration and stored at room temperature for 7 days in either standard bags (controls) or bags to which 1 or 2 g of Amberlite resin beads charged with dibasic phosphate had been added. The resin beads served as a buffer system by providing a "slow release" form of phosphate ions as well as by binding CO2 produced during platelet metabolism. Control platelets demonstrated rapid falls in pH, ATP content, morphology score, and thrombin-induced nucleotide release after 24 hr of storage with a fall in pH to less than 6.0 by day 3. Profound ultrastructural changes and a rise in pO2, suggesting loss of platelet viability, accompanied these changes. In contrast, the resin-stored platelets remained near normal after 24 hr of storage, with preservation of discoid morphology, 95% of ATP levels, excellent ultrastructural appearance, and evidence of continued oxygen consumption after 3 days of storage. Even after 7 days of storage, ATP levels remained greater than 50% of baseline and ultrastructurally intact platelets were seen. In the 1-g resin bags the pH remained at baseline levels (6.9-7.0), while there was a rise in pH in the 2-g resin bags. These results demonstrate the beneficial effects of maintaining a higher pH during platelet storage and provide a new approach to studying the metabolic changes that occur during longer term storage.     

New abnormalities in the morphology, cell surface receptors, and electrolyte metabolism of In(Lu) erythrocytes

The In(Lu) phenotype is inherited as an autosomal dominant trait and is characterized by suppression of the Lutheran, P1, i, and Aua erythrocyte blood group antigens. We have developed a monoclonal antibody (L21) that strongly agglutinates all erythrocytes except In(Lu), and we have identified eight In(Lu) individuals among 42,000 blood donors tested. Studies of two families confirmed the dominant mode of inheritance and revealed several new features of this phenotype. The erythrocytes of all five affected individuals from the two families exhibited diminished hemagglutination by the lectin concanavalin A, although they reacted normally with several other lectins. The erythrocytes of two affected individuals in one family exhibited marked acanthocytosis. The erythrocytes of the proposita of the other family exhibited a mild degree of poikilocytosis, but the cells of the other two affected individuals in this family had normal morphology. The osmotic fragility of fresh In(Lu) erythrocytes was normal, but after incubation for 24 hours at 37 degrees C in plasma the In(Lu) cells exhibited a marked increase in resistance to osmotic lysis. During the incubation period the erythrocytes lost K+ and their total cation content was diminished. These data indicate that in addition to the suppression of blood group antigens noted previously, the In(Lu) phenotype includes a variety of morphological abnormalities and a defect in electrolyte metabolism. The use of L21 and similar monoclonal antibodies provides a more sensitive means of detecting In(Lu) erythrocytes than typing with human anti-Lub antisera.     

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.