Vesicular pityriasis rosea: response to erythromycin treatment

Pityriasis rosea (PR) is a relatively common disease although its aetiology has not yet been identified. It occurs worldwide and there is no racial susceptibility factor. It usually affects teenagers and young adults between 10 and 35 years of age. Typical PR is much easier to diagnose than the rare atypical forms. We report a rare case of vesicular PR in a black woman who had vesicular lesions limited to her palms and soles in addition to regular typical lesions. We devised an efficient oral erythromycin treatment for this patient.     

环孢菌素A阻断人HL－60抗药性细胞于G_1期而诱导敏感细胞凋亡

进一步研究了抗三尖杉酯碱的ＨＬ－６０细胞（ＨＲ２０）抗细胞凋亡的机制及该抗性和抗药性的关系。结果表明，环孢菌素Ａ（ＣｓＡ）２０，１０μｇ·ｍｌ￣（－１）诱导ＨＬ－６０细胞发生凋亡，而阻断ＨＲ２０细胞于Ｇ＿１期，就不能诱导细胞发生凋亡。低浓度的ＣｓＡ明显增加柔红霉素在ＨＲ２０细胞内的积聚，其逆转抗药性作用与阻断细胞周期运行无关。ＣｓＡ１０μｇ·ｍｌ￣（－１）处理ＨＲ２０细胞，可引起５０ｋＤａ的蛋白质高度磷酸化。结果提示：环孢菌素Ａ阻断抗三尖杉酯碱的ＨＬ－６０细胞于Ｇ＿１期，而诱导敏感的ＨＬ－６０细胞发生凋亡，其阻断作用与抗药性无关     

Use of tissue recombination to predict phenotypes of transgenic mouse models of prostate carcinoma

Transgenic mouse models of cancer represent a powerful approach for exploring disease processes and testing potential therapeutic interventions. Currently, it is difficult to predict if a specific genetic manipulation will result in a desirable phenotype. The present study tests the idea that tissue recombinants recapitulate the pathologic features of the neoplastic prostate seen in transgenic mice, and would thus be suitable predictive models for new mouse design. The large probasin-large T-antigen (LPB-Tag) transgenic lines 12T-7f and 12T-10 were used as a basis for this study. Tissue recombinants of bladder epithelium (BlE) and urogenital sinus mesenchyme (UGM) were implanted under the renal capsule of athymic mice. Recombinants composed of BlE from 12T-10 LPB-Tag and wild-type (wt) UGM faithfully recapitulated the histopathologic and temporal features of intact transgenic mice of this line. Tissue recombinants using BlE from 12T-7f mice and wt UGM developed epithelial proliferation with atypia that lacked the associated hypercellular stroma seen in the intact 12T-7f line. Recombinants using 12T-7f UGM demonstrated that the hypercellular stroma results from stromal cell expression of the SV40 large T antigen. Corresponding to the recombinant phenotypes, stromal Tag immunostaining was observed in prostate tissues from intact 12T-7f but not 12T-10 mice. Similar stromal expression of Tag was also noted in the hypercellular TRAMP prostatic stroma. Further analysis revealed a previously unreported pattern of SV40T expression in the LADY and TRAMP models including ductus deferens and seminal vesicle stroma as well as region and cell type-specific patterns in the epididymis. The present study demonstrates the utility of using tissue recombination to explore organ-specific phenotypes. Recombination strategies should enable quick and cost-effective screening for likely phenotypes in transgenic animals. This comparison of tissue recombination to existing models shows that this approach can elicit new information on well-characterized models.     

Decreased expression of phospholipase C-beta 2 isozyme in human platelets with impaired function

Platelets from a patient with a mild inherited bleeding disorder and abnormal platelet aggregation and secretion show reduced generation of inositol 1,4,5-trisphosphate, mobilization of intracellular Ca2+, and phosphorylation of pleckstrin in response to several G protein mediated agonists, suggesting a possible defect at the level of phospholipase C (PLC) activation (see accompanying report). A procedure was developed that allows quantitation of platelet PLC isozymes. After fractionation of platelet extracts by high-performance liquid chromatography, 7 out of 10 known PLC isoforms were detected by immunoblot analysis. The amount of these isoforms in normal platelets decreased in the order PLC- gamma 2 > PLC-beta 2 > PLC-beta 3 > PLC-beta 1 > PLC-gamma 1 > PLC- delta 1 > PLC-beta 4. Compared with normal platelets, platelets from the patient contained approximately one-third the amount of PLC-beta 2, whereas PLC-beta 4 was increased threefold. These results suggest that the impaired platelet function in the patient in response to multiple G protein mediated agonists is attributable to a deficiency of PLC-beta 2. They document for the first time a specific PLC isozyme deficiency in human platelets and provide an unique opportunity to understand the role of different PLC isozymes in normal platelet function.     

Red cell membrane stiffness in iron deficiency

The purpose of this study was to characterize red blood cell (RBC) deformability by iron deficiency. We measured RBC deformability to ektacytometry, a laser diffraction method for determining the elongation of suspended red cells subjected to shear stress. Isotonic deformability of RBC from iron-deficient human subjects was consistently and significantly lower than that of normal controls. In groups of rats with severe and moderate dietary iron deficiency, RBC deformability was also reduced in proportion to the severity of iron deficiency. At any given shear stress value, deformability of resealed RBC ghosts from both iron-deficient humans and rats was lower than that of control ghosts. However, increase of applied shear stress resulted in progressive increase in ghost deformation, indicating that ghost deformability was primarily limited by membrane stiffness rather than by reduced surface area-to-volume ratio. This was consistent with the finding that iron-deficient cells had a normal membrane surface area. In addition, the reduced mean corpuscular hemoglobin concentration (MCHC) and buoyant density of the iron-deficient rat cells indicated that a high hemoglobin concentration was not responsible for impaired whole cell deformability. Biochemical studies of rat RBC showed increased membrane lipid and protein crosslinking and reduced intracellular cation content, findings that are consistent with in vivo peroxidative damage. RBC from iron-deficient rats incubated in vitro with hydrogen peroxide showed increased generation of malonyldialdehyde, an end-product of lipid peroxidation, compared to control RBC. Taken together, these findings suggest that peroxidation could contribute in part to increased membrane stiffness in iron- deficient RBC. This reduced membrane deformability may in turn contribute to impaired red cell survival in iron deficiency.     

Atypical Femoral Fractures: Transverse Morphology at Lateral Cortex Is a Critical Feature

In 2010, the American Society for Bone and Mineral Research (ASBMR) task force defined major and minor features to assist in the case finding and reporting of atypical femoral fractures (AFFs). One major feature that was proposed was a “transverse or short oblique configuration.” Our primary aim was to compare the conventional overall fracture morphology (OFM) with its associated angle (OFMA) and our proposed lateral cortical fracture angle (LCFA) in the assessment of fracture configuration in suspected AFFs and non‐AFFs. The radiographs of 79 patients with AFFs and 39 patients with non‐AFFs were each analyzed by two blinded reviewers to obtain the OFM, OFMA, and LCFA. Using the overall fracture morphology to assess the suspected AFFs resulted in discordance between reviewers in 18 cases (22.8%), of which 5 (6.3%) were discordant between short oblique (>30° to 60°) and long oblique (>60° to 90°) configurations, therefore affecting their classifications as AFFs. By assessing only the critical component within the lateral cortex, all the suspected AFFs fell well within the classification as transverse fractures with a mean LCFA of 4.8° (range 0.3 to 18.0, SD = 4.23). The inter‐reader variability was also lower for LCFA versus OFMA (4.1° versus 6.9°, p = 0.001) when used to assess AFFs. Fracture angles were significantly different in AFFs versus non‐AFFs regardless of whether the OFMA or LCFA methodology was employed, but the greater difference associated with LCFA suggests its greater discriminating power. When LCFA was used in conjunction with 0° to 30° as the criteria for transverse morphology, all the AFFs and non‐AFFs were correctly classified. By using a standardized and precise method in measuring the fracture angle, specifically using only the component of the lateral cortex and limiting to truly transverse fractures, ie, between 0° and 30°, the LCFA is a robust and accurate method to assess the fracture morphology in suspected AFFs. © 2014 American Society for Bone and Mineral Research.