Interleukin-1-inhibitor activity induced by respiratory syncytial virus: abrogation of virus-specific and alternate human lymphocyte proliferative responses

Respiratory syncytial virus (RSV) infection has been shown to induce human mononuclear leukocyte (MNL) production of net interleukin-1 (IL-1)-inhibitor activity. In the current studies of IL-1-inhibitor effects, RSV-exposed cells were compared with autologous MNL that were sham-exposed or exposed to inactivated RSV or influenza virus (which induces net IL-1 activity and commonly elicits effective homotypic immunity). Exposure of MNL to influenza virus or inactivated RSV resulted in increased expression of human leukocyte antigen-DR, the IL-2 receptor, and the transferrin receptor and increased progression through the cell cycle by 3 days. In contrast, exposure to infectious RSV resulted in decreased marker expression and cell cycle arrest, with abrogation of proliferation in response to the virus or other stimuli. These data raise the possibility that a contributing mechanism for recurrence of RSV infection is early suppression of the clonal expansion of virus-specific lymphocytes due to net IL-1-inhibitor activity.     

Age and gender effects in EEG coherence: III. Girls with attention-deficit/hyperactivity disorder.

OBJECTIVE: This study investigated intrahemispheric and interhemispheric EEG coherences as a function of age in girls with different DSM-IV subtypes of Attention-Deficit/Hyperactivity Disorder (AD/HD). It completes a series of 3 studies aimed at clarifying developmental and gender impacts on the coupling between brain regions in this disorder. METHODS: Three groups of 40 children (AD/HD combined type, AD/HD inattentive type, and normal controls) participated. Each group contained 8 females in each of 5, 1-year age bands from 8 to 12 years. EEG was recorded from 21 sites during an eyes-closed resting condition. Wave-shape coherence was calculated for 8 intrahemispheric electrode pairs (4 in each hemisphere), and 8 interhemispheric electrode pairs, within each of the delta, theta, alpha and beta bands. RESULTS: Developmental effects in intrahemispheric coherences at shorter and longer inter-electrode distances were not as predicted by Thatcher's two-compartment model, contrary to previous findings in boys. Females with AD/HD showed evidence of developmental delay and widespread anomalous elevations in coherence. Girls with AD/HD of the combined type showed similar but greater anomalies than girls with AD/HD of the inattentive type. CONCLUSIONS: Girls with AD/HD show coherence anomalies relative to age- and gender-matched controls, which differ substantially from those shown by boys with AD/HD. These coherence anomalies did not differ in nature between girls with different DSM-IV subtypes of AD/HD, suggesting that subtype differences in girls reflect only symptom severity. SIGNIFICANCE: The data reported here indicate qualitative differences in EEG coherences in girls with AD/HD compared with controls, and quantitative differences between girls with different subtypes of AD/HD. Both sets of effects differ in nature from those previously found in boys with AD/HD, showing the need to carefully consider gender in future studies of AD/HD.     

Laboratory evaluation of alignment and kinematics in a unicompartmental knee arthroplasty inserted with intramedullary instrumentation.

The purposes of this study were to evaluate the reliability of intramedullary (IM) instrumentation for unicompartmental total knee replacement and to assess the stability characteristics of the knee after implantation of a relatively unconstrained articular surface. Five adult, human cadaver lower extremities including hip, knee, and ankle were used to evaluate IM alignment. Five adult, fresh-frozen knee specimens were used to evaluate knee kinematics. Long anterioposterior roentgenograms were used to evaluate valgus angle and position of the center of the knee relative to the mechanical axis of the lower extremity. IM instrumentation returned the knee to normal alignment in all cases. The greatest valgus angle change was 3 degrees, and the position of the center of the knee relative to the mechanical axis was not significantly altered. Knee kinematics after unicompartmental knee replacement followed the predicted pattern of normal stability in extension and had slightly less varus-valgus laxity at 30 degrees (p less than 0.01), 45 degrees (p less than 0.01), and 60 degrees (p less than 0.05), and less anteroposterior displacement at 45 degrees (p less than 0.01) and 60 degrees (p less than 0.05). This study offers encouraging evidence that unicompartmental knee replacement with unconstrained components can restore normal knee kinematics, and that alignment can be restored with a high degree of accuracy with an intramedullary alignment system.     

Bone density ligand, Sclerostin, directly interacts with LRP5 but not LRP5G171V to modulate Wnt activity.

We compared and contrasted the mechanism of action for the cysteine knot protein subfamily, Wise and Sost (Sclerostin). Our data suggest that functional interactions between Sost or Wise and LRP5/LRP6 have the potential to regulate bone deposition by modulating the Wnt pathway. INTRODUCTION: The human disease sclerosteosis exhibits an increase in bone mass thought to be caused by hyperactive osteoblasts. Sclerostin, SOST, the gene affected in this disease, has been postulated to exert its activity by functioning as a BMP antagonist. However, recent evidence indicates that SOST is highly related to Wise, which can also modulate the Wnt pathway by binding to LRP5 and LRP6. MATERIALS AND METHODS: For this study, we used cell culture to test the BMP and Wnt activity function of both Wise and Sost. In addition, we used Xenopus in vivo Wnt assays along with Xenopus in vitro Wnt assays to support our cell culture results. Epitope tagged cell supernatants containing either Sost or soluble mutant or wildtype LRP5/LRP6 were used for immunoprecipitation. Sost immunoprecipitation results were confirmed in vivo using cell culture. Finally, to support our in vitro data, we co-localized Sost, Wise, LRP5, and LRP6 in mouse long bone sections. Results: In this study, we report in vitro and in vivo evidence to show that Sost physically interacts with Lrp5 and Lrp6 and inhibits the canonical Wnt signaling pathway. Furthermore, using in vitro and in vivo assays, we showed that a variant of LRP5 (LRP5(G171V)) known to cause the human high bone mass (HBM) trait and a homologous change in LRP6 (LRP6(G158V)) abolished protein interactions with Sost. We used variants of Sost amino acids to further identify the contact points between Sost and LRP6. In Xenopus and mammalian cell culture assays, we showed that SOST is able to attenuate Wnt signaling and that this attenuation can be rescued by the addition of alpha-Sost antibodies or by the introduction of single amino acid substitution that alter its binding to LRP6. Sost differs from Wise in that it is unable to stimulate Wnt signaling. Using immunohistochemistry, we found that Sost and Wise are co-localized to osteoblasts, along with LRP5 and LRP6. CONCLUSIONS: Our data suggest that functional interactions between Sost or Wise and LRPs have the potential to regulate bone deposition by modulating Wnt signaling.     

Preemptive Plasmapheresis and Recurrence of FSGS in High-Risk Renal Transplant Recipients

Recurrent focal segmental glomerulosclerosis (FSGS) following transplantation is ascribed to the presence of a circulating FSGS permeability factor (FSPF). Plasmapheresis (PP) can induce remission of proteinuria in recurrent FSGS. This study addressed the efficacy of pre-transplant PP in decreasing the incidence of recurrence in high-risk patients. Ten patients at high-risk for FSGS recurrence because of rapid progression to renal failure (n = 4) or prior transplant recurrence of FSGS (n = 6) underwent a course of 8 PP treatments in the peri-operative period. Recurrences were identified by proteinuria >3 g/day and confirmed by biopsy. Seven patients, including all 4 with first grafts and 3 of 6 with prior recurrence, were free of recurrence at follow-up (238-1258 days). Final serum creatinine in 8 patients with functioning kidneys averaged 1.53 mg/dL. FSGS recurred within 3 months in 3 patients, each of whom had lost prior transplants to recurrent FSGS. Two of these progressed to end-stage renal disease (ESRD) and the third has significant renal dysfunction. Based on inclusion criteria, recurrence rates of 60% were expected if no treatment was given. Therefore, PP may decrease the incidence of recurrent FSGS in high-risk patients. Definitive conclusions regarding optimal management can only be drawn from larger, randomized, controlled studies.     

The timing of surgical intervention in craniofacial anomalies

When treating an infant or younger child with severe craniofacial synostosis, the burden is placed on the surgeon in making a decision regarding not only the design of the osteomy but also the timing of the surgical intervention. This article reviews the current treatment protocols for craniofacial anomalies.     

闭经

闭经指育龄期妇女月经未来潮。导致闭经的病因很多,有病理性和生理性两类。病理性原因导致的闭经多见于原发性闭经,解剖原因所致的闭经少见但也很重要。妊娠和哺乳期闭经属生理性闭经。闭经通常分为原发性和继发性闭经两种。原发性闭经指16岁时仍无月经来潮,而继发性闭经是指≥6个月无月经来潮。导致闭经原因常常多个混杂,所以区别两者的实际意义不大。导致闭经的内分泌因素包括:多囊卵巢综合征、紧张和劳累、体重相关、高泌乳素血症、心理性疾病、全身性疾病如:肾功能衰竭、药物因素、卵巢早衰、垂体缺血性坏死、原发性下丘脑-垂体-卵巢(H…