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The structure of a colored intermediate commonly formed in the oxidation of p-aminophenol at low pH is established by analysis of H NMR and UV/vis spectra, kinetics, and molecular modeling, following a new method for synthesizing the dye in high concentrations. The chromogen is shown to consist of two compounds with absorption maxima at 540-560 and 375-385 nm. The 2,6-dimethyl and 3,5-dimethyl analogues of p-aminophenol are found to undergo N- rather than C-substitution under similar conditions.

Interruption of suppressive highly active antiretroviral therapy (HAART) in HIV-infected patients leads to increased HIV replication and viral rebound in peripheral blood. Effects of therapy interruption on gut-associated lymphoid tissue (GALT) have not been well investigated. We evaluated longitudinal changes in viral replication and emergence of viral variants in the context of T cell homeostasis and gene expression in GALT of three HIV-positive patients who initiated HAART during primary HIV infection but opted to interrupt therapy thereafter. Longitudinal viral sequence analysis revealed that a stable proviral reservoir was established in GALT during primary HIV infection that persisted through early HAART and post-therapy interruption. Proviral variants in GALT and peripheral blood mononuclear cells (PBMCs) displayed low levels of genomic diversity at all times. A rapid increase in viral loads with a modest decline of CD4 + T cells in peripheral blood was observed, while gut mucosal CD4 + T cell loss was severe following HAART interruption. This was accompanied by increased mucosal gene expression regulating interferon (IFN)-mediated antiviral responses and immune activation, a profile similar to those found in HAART-naive HIV-infected patients. Sequence analysis of rebound virus suggested that GALT was not the major contributor to the postinterruption plasma viremia nor were GALT HIV reservoirs rapidly replaced by HIV rebound variants. Our data suggest an early establishment and persistence of viral reservoirs in GALT with minimal diversity. Early detection of and therapy for HIV infection may be beneficial in controlling viral evolution and limiting establishment of diverse viral reservoirs in the mucosal compartment.

Despite the remarkable healing potential of long bone fractures, traumatic injuries that result in critical defects require challenging reconstructive limb sparing surgery. While devitalized allografts are the gold standard for these procedures, they are prone to failure due to their limited osseointegration with the host. Thus, the quest for adjuvants to enhance allograft healing remains a priority for this unmet clinical need. To address this, we investigated the effects of daily systemic injections of 40 μg/kg teriparatide (recombinant human parathyroid hormone) on the healing of devitalized allografts used to reconstruct critical femoral defects (4mm) in C57Bl/6 mice. The femurs were evaluated at 4 and 6 weeks using micro CT, histology, and torsion testing. Our findings demonstrated that teriparatide induced prolonged cartilage formation at the graft-host junction at 4 weeks, which led to enhanced trabeculated bone callus formation and remarkable graft-host integration at 6-weeks. Moreover, we observed a significant 2-fold increase in normalized callus volume (1.04 ± 0.3 vs. 0.54 ± 0.14 mm³/mm; p < 0.005), and Union Ratio (0.28 ± 0.07 vs. 0.13 ± 0.09; p < 0.005), compared to saline treated controls at 6-weeks. Teriparatide treatment significantly increased the torsional rigidity (1175 ± 311 versus 585 ± 408 N.mm²) and yield torque (10.5 ± 4.2 versus 6.8 ± 5.5 N.mm) compared to controls. Interestingly, the Union Ratio correlated significantly with the yield torque and torsional rigidity (R²=0.59 and R²=0.77, p < 0.001, respectively). These results illustrate the remarkable potential of teriparatide as an adjuvant therapy for allograft repair in a mouse model of massive femoral defect reconstruction, and warrant further investigation in a larger animal model at longer time intervals to justify future clinical trials for PTH therapy in limb sparing reconstructive procedures.

Purpose To study the use of an interleaved water-fat (IWF) sequence with a custom-made radiofrequency (RF) coil for high-resolution imaging of arthritic finger joints. Materials and Methods High-resolution finger magnetic resonance imaging (MRI) was performed using a custom-made dedicated RF receiver coil and an IWF sequence. A phantom, a cadaver finger specimen, and the fingers of two normal controls and six arthritic subjects were imaged with a resolution of 156 × 156 × 600 μm. The appearance of anatomic structures on the IWF images were compared with images acquired with a regular sequence. The images were reviewed by two musculoskeletal radiologists for the depiction of anatomical structures and for the presence of abnormalities. Results The high-resolution images revealed detailed structures of the finger joints not detectable using typical clinical resolution. The IWF sequence gave more realistic depiction of subchondral bone thickness, and avoided false bone erosions displayed in the regular sequence. It also allowed better visualization of ligaments and tendons. Conclusion This pilot study shows the feasibility and the potential usefulness of high-resolution IWF imaging for finger joint evaluation. This technique may be useful for the diagnosis and treatment assessment of arthritis, and for the study of joint disease pathogenesis. J. Magn. Reson. Imaging 2011;33:245–251. © 2010 Wiley-Liss, Inc.

Advances in biomaterial fabrication have introduced numerous innovations in designing scaffolds for bone tissue engineering. Often, the focus has been on fabricating scaffolds with high and interconnected porosity that would allow for cellular seeding and tissue ingrowth. However, such scaffolds typically lack the mechanical strength to sustain in vivo ambulatory stresses in models of load bearing cortical bone reconstruction. In this study, we investigated the microstructural and mechanical properties of dense PLA and PLA/beta-TCP (85:15) scaffolds fabricated using a rapid volume expansion phase separation technique, which embeds uncoated beta-TCP particles within the porous polymer. PLA scaffolds had a volumetric porosity in the range of 30 – 40%. With the embedding of beta-TCP mineral particles, the porosity of the scaffolds was reduced in half while the ultimate compressive and torsional strength were significantly increased. We also investigated the properties of the scaffolds as delivery vehicles for growth factors and gene delivery vectors in vitro and in vivo. The low surface porosity resulted in sub optimal retention efficiency of the growth factors, and burst release kinetics reflecting surface coating rather than volumetric entrapment, regardless of the scaffold used. When loaded with BMP2 and VEGF and implanted in the quadriceps muscle, PLA/beta-TCP scaffolds did not induce ectopic mineralization but induced a significant 1.8 fold increase in neo vessel formation. In conclusion, dense PLA/beta-TCP scaffolds can be engineered with enhanced mechanical properties and potentially be exploited for localized therapeutic factor delivery.

Measurement lies at the heart of quantum theory, and introductory textbooks in quantum mechanics cover the measurement problem in topics such as the Schrodinger's cat thought experiment, the EPR problem, and the quantum Zeno effect (QZE). In this article we present a new treatment of the QZE suitable for undergraduate students, for the case of a particle tunnelling between two wells while being observed in one of the wells. The analysis shows that as the observation rate increases, the tunnelling rate tends towards zero, in accordance with Zeno's maxim 'a watched pot never boils'. The method relies on decoherence theory, which replaces aspects of quantum collapse by the Schrodinger evolution of an open system, and its recently simplified treatment for undergraduates. Our presentation uses concepts familiar to undergraduate students, so that calculations involving many-body theory and the formal properties of the density matrix are avoided.

We re-evaluated the taxonomic status of the New Guinean subspecies weiskei of the Little Eagle Aquila morphnoides and confirmed that it differs considerably from the Australian A. morphnoides in multiple morphological and plumage characters. Genetic differentiation in published mitochondrial cyt-b and ND2 sequences between the nominate subspecies and weiskei is equivalent to that found between other accipitrid taxa at the species level, as are pairwise divergences between each Little Eagle taxon and their sister species, the Booted Eagle A. pennata. The available morphological and genetic evidence thus strongly and unambiguously supports the specific distinctness of A. weiskei. We propose the English name Pygmy Eagle, as this is the world’s smallest known eagle. We show that the distribution of A. weiskei includes the western part of New Guinea (Vogelkop) and the Moluccas (Halmahera, Ternate and Seram), based on our new observations.

Our objective was to characterize variations in mechanical knee alignment, tibial torsion, tibial width, and ACL laxity measurements between Japanese and Caucasian populations in the healthy, young adult knee joint. Seventy young adult subjects participated in this study, including 23 Japanese and 47 Caucasian subjects. Coronal magnetic resonance images of the hip, knee, and ankle were acquired for analysis. Japanese subjects had a significantly higher (p = 0.04) varus alignment (1.64 ± 0.43° standard error) than Caucasians (0.55 ± 0.33°), while women exhibited a more valgus alignment (0.16 ± 0.52°) than men (0.94 ± 0.42°, p = 0.04). Significant differences were found in tibial torsion and ACL laxity (p < 0.01) between ethnicities, with Japanese exhibiting lower tibial torsion (33.4 ± 10.0°) and higher ACL laxity (7.5 ± 0.4 mm) measurements compared to Caucasians (38.9 ± 9.5° and 5.7 ± 0.3 mm, respectively). Significant differences between genders were found in hip-knee-ankle alignment (p = 0.04), tibial width (p < 0.0001), and ACL laxity (p < 0.01) measurements. Measurements were reliable between observers and for repeated positioning. Our study provides new insight into anatomical and geometric differences in the knee joint between Japanese and Caucasians, as well as between females and males. Further consideration of these results may improve development of implants to accommodate for these differences, and understanding of characteristics leading to increased prevalence of knee OA in certain populations. The use of magnetic resonance imaging to obtain these measurements also allows soft tissue structure characterization without exposure to ionizing radiation. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res

Trabecular bone density changes throughout the proximal tibia are indicative of several musculoskeletal disorders of the knee joint. Many of these disorders involve not only changes in the amount of bone, but also in the surrounding soft tissue. Osteoarthritis, for instance, involves bone density changes below the subchondral bone and throughout the proximal tibia, along with degradation evident in the articular cartilage. Osteoporosis, characterized by low bone density may also involve changes in bone size, structure or microarchitecture, each of which may contribute to fracture risk. Recent studies have shown that magnetic resonance (MR) imaging, most frequently applied for soft tissue imaging, also allows non-invasive 3-dimensional characterization of bone microstructure. The purpose of the current study is to use whole joint MR images to acquire regional apparent bone volume fraction (appBVF) throughout the proximal tibia and correlate with mechanical properties measured on the corresponding ex vivo specimens. To compare our method to a high-resolution imaging modality, micro-CT analysis was performed in a subset of specimens. Using linear mixed-effects models, significant correlations (p0.05) were determined between MR appBVF and Young's modulus (r(2)=0.58, MPSE=3633 MPa(2)), yield stress (r(2)=0.73, MPSE=1.53 MPa(2)) and ultimate stress (r(2)=0.72, MPSE=2.29 MPa(2)). Comparable significant correlations (p0.05) were also determined between micro-CT BVF and Young's modulus (r(2)=0.47, MPSE=5179 MPa(2)), yield stress (r(2)=0.80, MPSE=1.23 MPa(2)) and ultimate stress (r(2)=0.83, MPSE=1.76 MPa(2)). The current study demonstrates that MR imaging may be used as an in vivo imaging tool to determine differences in bone strength between subjects and regional variations within a single tibia.

Phylogenetic relationships among birds of prey in the subfamily Buteoninae are not fully established but are of particular interest because the Buteoninae constitute one of the largest accipitrid subgroups and include multiple species of conservation concern. Genera previously included within the Buteoninae are Buteo, Leucopternis, Buteogallus, Harpyhaliaetus, Busarellus, Parabuteo, Geranoaetus, Geranospiza, Ictinia, Rostrhamus, Kaupifalco, and Butastur. We analyzed representatives from all buteonine genera and most non-Buteo (i.e., "sub-buteo") species with >3,000 bases of nuclear and mitochondrial DNA and found non-monophyly for the nominal genera Buteo, Buteogallus, and Leucopternis. The Old World Lizard Buzzard (Kaupifalco monogrammicus) is not closely related to buteonine taxa but is sister to goshawks in the genera Melierax, Micronisus, and Urotriorchis. Another Old World genus, Butastur, is sister to the clade including all other buteonine genera mentioned above. Investigation of several "...

The objective of this study was to determine tibiofemoral cartilage thickness distribution, and to investigate the relationship between cartilage geometry and anthropometric variables. In this study, 20 magnetic resonance examinations of the knee from normal individuals were reconstructed to provide three-dimensional models of the knee joint, including bony and cartilage surfaces. Three regions were defined on the articular surface, and the cartilage thickness distribution along each of these was determined. Statistically significant differences between femoral and tibial regions were examined using the paired Student t test in Microsoft Excel. Correlations were investigated using the correlation tool in Microsoft Excel. The average tibial cartilage thickness was found to be 2.76 mm and the average femoral cartilage thickness was 2.75 mm. Significant correlations exist between the tibia cartilage thickness and body height ( R = 0.60; P It is suggested that the distribution and correlations of cartilage distribution indicate adaptation in response to mechanical loading. Information regarding cartilage thickness and volume distribution as found in this study may be useful in diagnosing and monitoring cartilage loss in patients with degenerative joint disease.

Use of computational models with kinematic boundary conditions to study the knee joint contact behavior for normal and pathologic knee joints depends on an understanding of the impacts of kinematic uncertainty. We studied the sensitivities of tibio-menisco-femoral joint contact behavior to variations in knee kinematics using a finite element model (FEM) with geometry and kinematic boundary conditions derived from sequences of magnetic resonance (MR) images. The MR images were taken before and after axial compression was applied to the knee joint of a healthy subject. A design of experiments approach was used to study the impact of the variation in knee kinematics on the contact outputs. We also explored the feasibility of using supplementary hip images to improve the accuracy of knee kinematics. Variations in knee kinematics (0.25mm in medial-lateral, 0.1mm in anterior-posterior and superior-inferior translations, and 0.1 degrees in flexion-extension and varus-valgus, 0.25 degrees in external-internal rotations) caused large variations in joint contact behavior. When kinematic boundary conditions resulted in close approximations of the model-predicted joint contact force to the applied force, variations in predictions of contact parameters were also reduced. The combination of inferior-superior and medial-lateral translations accounted for over 70% of variations for all the contact parameters examined. The inclusion of hip images in kinematic calculations improved knee kinematics by matching the femoral head position. Our findings demonstrate the importance of improving the accuracy and precision of knee kinematic measurements, especially when utilized as an input for finite element models.

The purpose of this study was to clarify meniscal displacement and cartilage-meniscus contact behavior in a full extension position and a deep knee flexion position. We also studied whether the meniscal translation pattern correlated with the tibiofemoral cartilage contact kinematics. Magnetic resonance (MR) images were acquired at both positions for 10 subjects using a conventional MR scanner. Subjects achieved a flexion angle averaging 139 degrees +/- 3 degrees. Both medial and lateral menisci translated posteriorly on the tibial plateau during deep knee flexion. The posterior translation of the lateral meniscus (8.2 +/- 3.2 mm) was greater than the medial (3.3 +/- 1.5 mm). This difference was correlated with the difference in tibiofemoral contact kinematics between medial and lateral compartments. Contact areas in deep flexion were approximately 75% those at full extension. In addition, the percentage of area in contact with menisci increased significantly due to deep flexion. Our results related to meniscal translation and tibio-menisco-femoral contact in deep knee flexion, in combination with information about force and pressure in the knee, may lead to a better understanding of the mechanism of meniscal degeneration and osteoarthritis associated with prolonged kneeling and squatting.

We have shown that preoperative thrombocytosis (platelet counts400 x 10(9)/l) is an independent poor prognostic factor in epithelial ovarian cancers (EOC) and is associated with worse survival. In light of the similarities between uterine papillary serous carcinomas (UPSC) and EOC, we sought to determine the incidence of thrombocytosis in UPSC and examine associations with clinico-pathologic features and survival.68 patients with UPSC were identified between 1996 and 2004 at 3 institutions. After IRB approval, records were retrospectively reviewed and data analyzed using Chi-squared and Cox proportional hazards model; survival was analyzed by the method of Kaplan and Meier.8/68 (12%) patients had thrombocytosis at primary diagnosis. Patients with thrombocytosis were found to have more advanced stage disease (p=0.002) and ascites1 L (p0.0001). Of the 21 patients with stage IV disease, those with normal preoperative platelet counts demonstrated a greater likelihood of optimal tumor resection to less than 1 cm residual disease (13/15 versus 1/6 in patients with thrombocytosis, p0.002). Patients with thrombocytosis had a shorter disease-free interval (17 months versus median survival not yet reached, p=0.0067) and overall survival (24 versus 45 months, p=0.0026). On multivariate analysis, thrombocytosis retained significance as a poor prognostic indicator in patients after controlling for age and stage (p=0.04).Thrombocytosis may be a marker of aggressive tumor biology in UPSC. Platelet-secreted growth factors may promote aggressive cancer phenotype through contribution to metastasis, invasion, and primary tumor growth.

Many scoring systems have been developed that serve to evaluate outcomes following total hip arthroplasty (THA). However, most systems focus on specific aspects of a patient's recovery rather than investigating a broad spectrum of parameters, which prevent physicians from obtaining a sufficient impression of a patient's recovery. Therefore, we evaluated existing scoring systems to assess the outcome categories included and parameters of interest.We examined all hip scoring systems currently available in the literature. The outcomes measured in each scoring system were sub-classified into one of four categories; subjective, objective, rehabilitative, and quality of life. We determined the number of scoring systems that incorporated each of these four categories and we assessed the most common parameters in each. The categories and individual parameters were assigned a relative weighted mean score based on how often they were incorporated, in an effort to determine their importance.We identified 42 hip scoring systems consisting of 44 individual parameters, which were divided into the above four categories. Of the relevant scoring systems, 74% included subjective parameters, 31% included objective parameters, 90% included rehabilitative parameters, and 62% included quality of life parameters. The most commonly assessed subjective parameters include pain, stiffness, and general hip difficulty. The most commonly assessed objective parameters include general/combined ROM, flexion/extension, and abduction/adduction. The most commonly assessed rehabilitative parameters include the ability to walk, the ability to climb stairs, and the ability to reach to the floor. The most commonly assessed quality of life measures include the ability to use a car, performance of light domestic duties, and performance of heavy domestic duties. The category of rehabilitative practices carried the greatest weighted mean (49%) in hip scoring systems, followed by subjective (40%), quality of life (6%), and objective (5%). With regard to individual hip outcome parameters, pain carried the greatest weighted mean (23%), followed by the ability to walk and the ability to perform general activities (11% each).Patient outcomes can be evaluated by the use of scoring systems in an effort to determine the effectiveness of THA in regaining function and improving quality of life. Determining the frequency and importance of parameters in current scoring systems may allow for a more accurate and purposeful assessment of post-operative function and patient satisfaction. Understanding what is evaluated in existing scoring systems may shed light on the future development of a comprehensive outcome questionnaire.

Because engineering is an applied science that often aims to create tangible objects such as machines, electronic circuits, and buildings, the meaning of design has come to be synonymous with the object of intention, the Design. Thus, the goal of a design course has traditionally been the conceptualization and reduction to practice of a useful physical object. However, a definition of design limited to the object for an intended use, does not adequately recognize that design is a process and not necessarily an endpoint. Therefore, for the purpose of this paper: Design in biomedical engineering means the conception, creation, and/or fabrication of devices, instruments, fixtures, procedures, methods, algorithms, or simulations intended to benefit health and wellness, including means to interrogate, analyze, or otherwise define operating or physical parameters. In BME, the design process occurs in the context of essential constraints, including regulatory, economic, environmental, sustainability, manufacturability, ethical, and socio-political factors.

This study investigated the role of the material properties assumed for articular cartilage, meniscus and meniscal attachments on the fit of a finite element model (FEM) to experimental data for meniscal motion and deformation due to an anterior tibial loading of 45 N in the anterior cruciate ligament-deficient knee. Taguchi style L18 orthogonal arrays were used to identify the most significant factors for further examination. A central composite design was then employed to develop a mathematical model for predicting the fit of the FEM to the experimental data as a function of the material properties and to identify the material property selections that optimize the fit. The cartilage was modeled as isotropic elastic material, the meniscus was modeled as transversely isotropic elastic material, and meniscal horn and the peripheral attachments were modeled as noncompressive and nonlinear in tension spring elements. The ability of the FEM to reproduce the experimentally measured meniscal motion and deformation was most strongly dependent on the initial strain of the meniscal horn attachments (epsilon(1H)), the linear modulus of the meniscal peripheral attachments (E(P)) and the ratio of meniscal moduli in the circumferential and transverse directions (E(theta)E(R)). Our study also successfully identified values for these critical material properties (epsilon(1H) = -5%, E(P) = 5.6 MPa, E(theta)E(R) = 20) to minimize the error in the FEM analysis of experimental results. This study illustrates the most important material properties for future experimental studies, and suggests that modeling work of meniscus, while retaining transverse isotropy, should also focus on the potential influence of nonlinear properties and inhomogeneity.

Purpose: The androgen receptor (AR) harbors a polymorphic CAG repeat sequence in exon 1, coding for a polyglutamine tract whose length inversely correlates with AR transactivation function. AIB1, an AR coactivator, expresses a similar polymorphic glutamine sequence within the carboxyl-terminal coding region. We hypothesized that genotypic variations in the androgen-signaling pathway promote aggressive epithelial ovarian cancer biology, and sought to examine the effect of AIB1 genotype on clinical outcome. Experimental Design: Genotype analysis of the AIB1 CAG repeat region was done on 89 patients with epithelial ovarian cancer. Medical records were reviewed for clinicopathologic factors and survival. Data were examined using the χ2 test and Kaplan-Meier survival and Cox regression analyses. Results: We identified four AIB1 genotypes, with glutamine codon lengths of 26, 28, 29, and 30. Patients with a short AIB1 genotype (with ≤28 CAG repeats) showed statistically shorter time to disease recurrence compared to those with a long genotype (≥29 CAG repeats; 15.0 versus 30.0 months; P = 0.01). Patients with short AIB1 also showed decreased overall survival (57.0 months) compared to those with a long genotype (median survival not yet reached; P = 0.02). When controlling for established prognostic factors, multivariate analysis identified the presence of a short AIB1 genotype as an independent poor prognostic factor for overall survival (P = 0.05). Conclusions: These data suggest that short AIB1 genotypes may promote aggressive malignant phenotypes of epithelial ovarian cancer. (Cancer Epidemiol Biomarkers Prev 2005;14(12):2919–22)

The menisci are believed to play a stabilizing role in the ACL-deficient knee, and are known to be at risk for degradation in the chronically unstable knee. Much of our understanding of this behavior is based on ex vivo experiments or clinical studies in which we must infer the function of the menisci from external measures of knee motion. More recently, studies using magnetic resonance (MR) imaging have provided more clear visualization of the motion and deformation of the menisci within the tibio-femoral articulation. In this study, we used such images to generate a finite element model of the medial compartment of an ACL-deficient knee to reproduce the meniscal position under anterior loads of 45, 76, and 107N. Comparisons of the model predictions to boundaries digitized from images acquired in the loaded states demonstrated general agreement, with errors localized to the anterior and posterior regions of the meniscus, areas in which large shear stresses were present. Our model results suggest that further attention is needed to characterize material properties of the peripheral and horn attachments. Although overall translation of the meniscus was predicted well, the changes in curvature and distortion of the meniscus in the posterior region were not captured by the model, suggesting the need for refinement of meniscal tissue properties.

Introduction Remodeling of gap junctions has been implicated in development of ventricular arrhythmias following myocardial infarction (MI) but the specific contribution of reduced electrical coupling is not known. We addressed this question using hearts from mice heterozygous for a connexin43 null allele (Cx43 +/− ). Methods To determine whether Cx43-deficient mice exhibit increased spontaneous ventricular arrhythmias in the setting of chronic ischemic heart disease, radiofrequency transmitters were implanted in wild-type and Cx43 +/− mice 2 days or 9 weeks after left anterior descending coronary artery ligation or sham operations. ECGs were recorded from unanesthetized, unrestrained mice 1 and 10 weeks after MI. Isolated, perfused hearts excised 1 and 10 weeks after MI were subjected to programmed electrical stimulation to induce arrhythmias. Results and conclusions Hearts with infarcts exhibited more spontaneous and inducible arrhythmias, but there was no significant difference between wild-type and Cx43-deficient mice. Fewer hearts exhibited spontaneous ventricular tachycardia (VT) in vivo than were inducible in vitro, suggesting that structural and functional substrates for inducible VT in isolated hearts may not be sufficient for initiation and maintenance of sustained VT in vivo. Previous studies have shown that Cx43-deficient mice exhibit more VT than wild-type mice during acute regional ischemia. Mice with MI exhibit increased arrhythmias. However, reduced coupling in Cx43-deficient mice does not significantly enhance spontaneous or inducible VT after MI.

The stress-activated protein kinase, c-Jun N-terminal kinase (JNK), has been implicated in the process of cardiac hypertrophy and apoptosis, yet the specific roles of JNK in heart failure are unclear. To determine the effects of JNK activation in intact heart, we established transgenic animals using a Cre/loxP-mediated gene switch approach to achieve targeted expression of an upstream activator, mitogen-activated protein kinase kinase 7 (D) (MKK7D), in ventricular myocytes. MKK7D expression led to significant JNK activation, robust induction of the fetal gene program, and contractile dysfunction. The animals died approximately 7 weeks after birth with signs of congestive heart failure. Doppler mode echocardiography revealed a marked stiffening of JNK-activated hearts that was associated with the remodeling of specific extracellular matrix components. Gene expression analysis of MKK7D hearts revealed up-regulation of transforming growth factor beta signaling, offering a potential molecular mechanism underlying changes in extracellular matrix composition. In addition, we demonstrated that JNK activation led to specific loss of connexin 43 protein and gap junctions without affecting the expression or localization of other key intercalated disc proteins. This specific and localized gap junction remodeling resulted in significant slowing of ventricular electrical conduction in JNK-activated hearts. These results represent the first characterization of JNK-mediated cardiac pathology in vivo and support an important role for JNK signaling in specific aspects of cardiac remodeling in the pathogenesis of cardiac disease.

Specific chromosome aberrations in peripheral blood lymphocytes (PBLs) in chromosomes 9 and 11 may be associated with bladder cancer. To investigate this hypothesis, in this study, we used a whole-chromosome painting technique to detect chromosomal aberrations in PBLs from 100 patients with bladder cancer and 100 matched controls. We also used a locus-specific fluorescence in situ hybridization technique to study 9p21 and cyclin D1 gene (CCND1) aberrations in PBLs of 10 patients and 10 controls and in tumor tissues of 38 additional cases. The chromosome-painting analysis showed that there were more aberrations of chromosomes 9 and 11 in bladder cancer patients than in controls. When categorized by type, the number of deletions of 9p and of translocations of chromosome 11 was significantly higher in patients than in controls (P < 0.05). Stratified analysis showed a larger odds ratio (OR) for bladder cancer in individuals with either a 9p deletion or a chromosome 11 translocation/amplification and an even larger OR in individuals with both aberrations. Using locus-specific analysis, we found that 9p21 aberrations occurred more frequently in bladder cancer patients (12.1 per 1,000 interphase cells) than in controls (6.4 per 1,000 interphase cells, P < 0.05); CCND1 translocation and amplification were observed only in bladder cancer patients. Tumor tissue analysis showed that aberrations of 9p21 (40.0 per 100 interphase cells) and CCND1 (43.8 per 100 interphase cells) were very common. Thus, we concluded that 9p deletions and translocations of chromosome 11, especially at 9p21 and CCND1, are associated with bladder cancer.

Background Mannose-binding lectin (MBL), an acute-phase serum protein of hepatic origin, plays an essential protective role in host innate immunity in targeting microbial pathogens for destruction via opsonization, enhancement of phagocytosis and complement activation. MBL deficiency, characterized by low serum MBL, has been attributed to genetic mutations in both structural and promoter regions of the gene coding for the protein. Concomitant MBL deficiency in patients with chronic immunologic disease has been associated with increased susceptibility to complicating infections that may hasten disease progression. Objective Few cases of inherited MBL deficiency in adults and possible associations with recurrent infection have been reported. To address this issue, we investigated the MBL profile of four generations within a single adult family whose members have experienced a variety of persistent infections. Methods MBL serum levels and MBL genotypes of each participating family member were ascertained by enzyme-linked immunoadsorbent assay and reverse transcriptase-polymerase chain reaction, respectively. MBL complement activation, as measured by C4b deposition against mannan-coated wells, was assayed using an enzyme-linked immunoadsorbent assay. Routine immunologic and cellular tests were carried out to evaluate the immunologic status of each family member. Results Six of the 7 family members screened carried one or more of the variant MBL alleles in their genotype and had correspondingly low serum MBL and reduced ability to affect C4b opsonization. Medical histories of the participating family members revealed an array of mild to severe recurrent infections despite no apparent immunodeficiency. Conclusions Our studies show that MBL deficiency is an inherited characteristic and may be a crucial factor in maintaining immunologic health.

We use many-body quantum theory to calculate the decay rate of a quantum state in a junction barrier undergoing Coulombic interaction with a tunneling current flowing through the junction. The tunneling current effectively measures the junction state occupation, and we find the measurement generaly acts to increase the decay rate in the limit of small junction transmission coefficient.

Case report.To describe the knee kinematics and moments of a giving-way trial of a subject with an anterior-cruciate-ligament- (ACL) deficient knee relative to his non-giving-way trials and to healthy subjects during a step-down task.Episodes of giving way are believed to damage joint structures, therefore treatments aim to prevent giving-way episodes, yet few studies document giving-way events.The giving-way trial experienced by a 32-year-old male subject with ACL deficiency during a step-down task was compared to his non-giving-way trials (n = 5) and data from healthy subjects (n = 20). Position data collected at 60 Hz were combined with anthropometric data and ground reaction force data collected at 300 Hz to estimate knee displacement and 3-dimensional angles and net joint moments.The knee joint displacement was higher during the giving-way trial: from 4% to 32% of stance, reaching 9.0 mm at 18% of stance as compared to 1.6 +/- 0.7 mm for the non-giving-way trials. After 4% of stance, the knee flexion angle of the giving-way trial was 6.6 degrees higher than the non-giving-way trials and was associated with a higher knee extension moment. The knee frontal plane moment was near neutral during early stance of the giving-way trial in contrast to the non-giving way and healthy subjects which demonstrated a knee abduction moment.The response of this subject to the giving-way event suggests that higher knee flexion angles may enhance knee stability and, in reaction to the giving-way event, that knee extension moment may increase.

Based on the substrate transition state and our strategy to tackle the problem of drug resistance, a series of HIV/FIV protease (HIV /FIV PR) monocyclic inhibitors incorporating a 15- or 17-membered macrocycle with an equivalent P3 or P3′ group and a unique unnatural amino acid, (2 R , 3 S )-3-amino-2-hydroxy-4-phenylbutyric acid, have been designed and synthesized. In addition, based on the structure of TL3 with small P3/P3′ group, we have synthesized two conformationally restricted bicyclic inhibitors containing the macrocycle, which mimic the P1/P1′-P3/P3′ tripeptide [Phe-Val-Ala] of TL3. We have found that the contribution of the macrocycle in our monocyclic inhibitors is important to the overall activity, but the ring size does not affect the activity to a significant extent. Several inhibitors that were developed in this work, exhibit low nanomolar inhibitory activity against the wild-type HIV/FIV PR and found to be highly effective against some drug-resistant as well as TL3-resistant mutants of HIV PRs. Compound 15 , in particular, is the most effective cyclic inhibitor in hand to inhibit FIV replication in tissue culture at a concentration of 1.0 μg/mL (1.2 μM).

The use of magnetic resonance imaging has been proposed by many investigators for establishment of joint reference systems and kinematic tracking of musculoskeletal joints. In this study, the intraobserver and interobserver reliability of a strategy to establish anatomic reference systems using manually selected fiducial points were quantified for seven sets of MR images of the human knee joint. The standard error of the measurement of the intraobserver and interobserver errors were less than 2.6 degrees, and 1.2 mm for relative tibiofemoral orientation and displacement, respectively. An automated motion tracking algorithm was also validated with a controlled motion experiment in a cadaveric knee joint. The controlled displacements and rotations prescribed in our motion tracking validation were highly correlated to those predicted (Pearson's correlation = 0.99, RMS errors = 0.39 mm, 0.38 degree). Finally, the system for anatomic reference system definition and motion tracking was demonstrated with a set of MR images of in vivo passive flexion in the human knee.

The objective of this paper is to assess whether ovarian hyperstimulation and in vitro fertilization (IVF) are associated with increased risk of cancer development, using an historical cohort analysis of infertile women who attended the IVF unit, Lis Maternity Hospital Tel Aviv Medical Center, Tel Aviv, Israel. One thousand and 82 women participated in the IVF treatment program between 1984 and 1992. Cancer incidence rates were determined through the National Cancer Registry and were compared to the expected rates with respect to appropriate age and continent of birth. Twenty-one cases of cancer were observed as compared to 11 that were expected (SIR 1.91; 95% CI 1.18–2.91). When cancer cases that were diagnosed within one year of the IVF treatment were excluded from the analysis (SIR = 1.46; 95% CI 0.83–2.36), no significant excess risk of cancer was noted. We conclude that in this cohort of infertile women, the higher than expected cancer rate could not be attributed to IVF treatments. Special attention should be made to women who may be diagnosed with cancer during or shortly after IVF treatment.

The performance of polymer carbon-black composite chemical vapor sensors as a function of underlying electrode size and geometry has been studied. The sensor performance parameters investigated were sensor response magnitude to a toluene analyte (100, 500, and 1000 ppm), fundamental sensor noise in the presence of air, and two concentrations of toluene (100 and 500 ppm), and signal-to-noise ratio (100 and 500 ppm). An array of sensors with 42 different circular electrode configurations were designed, fabricated, and tested where electrode gap was varied from 10 to 500 /spl mu/m and the diameter of the sensors was varied from 30 to 2000 /spl mu/m. Each array of electrodes was coated with an approximately 1 /spl mu/m-thick layer of conducting polymer carbon-black composite with an insulating poly(alkylacrylate) polymer. The response magnitude, fundamental noise, and signal-to-noise ratio of each sensor was measured and compared to electrode geometry, such as electrode gap, aspect ratio, and overall size. No significant dependence of sensor response magnitude and noise to electrode configuration has been observed to be larger than the variation from sensor to sensor. However, the signal-to-noise ratio tended to decrease for sensors with the smallest scales.

Gene-targeting in mice is a powerful tool to define molecular mechanisms of ischemic heart disease that determine infarct size, postinfarct left ventricular (LV) remodeling, and arrhythmogenesis. Coronary ligation in mice is becoming a widely used model of myocardial infarction (MI), but the pathophysiologic consequences of MI in mice and its relevance to human MI have not been fully elucidated. To characterize structural and functional changes during evolving MI, we analyzed 2-dimensional-based reconstruction of the left ventricle by noninvasive echocardiography obtained 1 day and 1 week after surgical ligation of the left anterior descending coronary artery in mice. Sequential 2-dimensional short-axis cineloops of the left ventricle were used to measure LV mass, and LV volumes at end-diastole and end-systole. Echocardiographic infarct size was estimated by measuring the volume of akinetic LV segments. Histologic infarct size was measured by planimetry of 9 transverse sections of each heart. There was close correlation between the 2 methods (31% +/- 20% of LV mass and 34% +/- 17% of LV area, respectively; y =.83x + 7.9, r = 0.96, P

We calculate the rate for stimulated transitions with photon emission between two trapped bosonic gases in thermal equilibrium, for both the box and harmonic oscillator traps in the weak interaction limit. It is shown that stimulation has a peak at a temperature characteristic of the kinetic energy of final state bosons. The problem of nuclear γ- and β-decay stimulation is reanalysed and a possible method for obtaining observable results suggested.

Analysis of mice with genetically altered expression of cardiac connexins can provide insights into the role of individual gap junction channel proteins in cell-to-cell communication, impulse propagation, and arrhythmias. However, conflicting results have been reported regarding conduction velocity slowing in mice heterozygous for a null mutation in the gene encoding connexin43 (Cx43). Methods: High-resolution optical mapping was used to record action potentials from 256 sites, simultaneously, on the ventricular surface of Langendorff perfused hearts from 15 heterozygous (Cx43+/−) and 8 wildtype (Cx43+/+) mice (controls). A sensitive method for measuring epicardial conduction velocity was developed to minimize confounding influences of subepicardial breakthrough and virtual electrode effects. Results: Epicardial conduction velocity was significantly slower (23 to 35%, P

Time for primary review 28 days. Sudden cardiac death occurs with unacceptably high incidence in patients with ischemic heart disease and cardiomyopathy. As Zipes and Wellens [1] have emphasized, sudden death arises from highly variable interactions between anatomic and/or functional myocardial substrates, transient initiating events and cellular/tissue arrhythmia mechanisms. In our view, a key strategy for developing mechanistic insights into sudden death is to first define the role of individual factors (including specific gene products) that contribute to arrhythmias, and to then understand how these factors interact to cause sudden death. One of the most common disease settings leading to sudden cardiac death is the acute coronary syndromes. Acute ischemia is marked by alterations in cell metabolism, cell signaling, intercellular communication and electrical impulse propagation [2]. These changes produce a cascade of events that are adaptive in the sense that mechanisms are activated to mitigate injury, forestall cell death and isolate irreversibly injured myocytes from their viable neighbors, but also maladaptive in that they can create a substrate that supports the initiation and maintenance of malignant ventricular arrhythmias. Among the electrophysiologically relevant changes that occur rapidly after the onset of ischemia are reductions in tissue pH, increases in interstitial K+ and intracellular Ca2+ concentrations and changes in active and passive membrane properties, all of which interact in a complex milieu to slow conduction, alter excitability and refractoriness, promote electrical uncoupling, and generate spontaneous electrical activity [1–4]. In this review, we focus on the specific role of diminished intercellular electrical coupling in the pathogenesis of lethal arrhythmias induced by acute ischemia. Until recently, it has been difficult to isolate the contribution of diminished coupling per se to arrhythmogenesis in the complex setting of acute ischemia. However, the advent of techniques to manipulate gene expression and characterize cardiac …

We tested the hypothesis that cardiac allograft dysfunction in acute cardiac rejection may be related, in part, to diminished expression of connexin43, a gap junction channel protein that facilitates intercellular communication and coordinates electrical and mechanical cardiac function. We measured connexin43 levels using quantitative confocal immunofluorescence microscopy of endocardial biopsies from heart transplant recipients with histologic evidence of either no rejection or acute cellular rejection. Expression of connexin43 diminished significantly during acute cellular rejection and returned to baseline levels following resolution of rejection. Reversible down-regulation of connexin43 may contribute to ventricular dysfunction in allograft rejection.

Abstract —Electrical uncoupling at gap junctions during acute myocardial ischemia contributes to conduction abnormalities and reentrant arrhythmias. Increased levels of intracellular Ca 2+ and H + and accumulation of amphipathic lipid metabolites during ischemia promote uncoupling, but other mechanisms may play a role. We tested the hypothesis that uncoupling induced by acute ischemia is associated with changes in phosphorylation of the major cardiac gap junction protein, connexin43 (Cx43). Adult rat hearts perfused on a Langendorff apparatus were subjected to ischemia or ischemia/reperfusion. Changes in coupling were monitored by measuring whole-tissue resistance. Changes in the amount and distribution of phosphorylated and nonphosphorylated isoforms of Cx43 were measured by immunoblotting and confocal immunofluorescence microscopy using isoform-specific antibodies. In control hearts, virtually all Cx43 identified immunohistochemically at apparent intercellular junctions was phosphorylated. During ischemia, however, Cx43 underwent progressive dephosphorylation with a time course similar to that of electrical uncoupling. The total amount of Cx43 did not change, but progressive reduction in total Cx43 immunofluorescent signal and concomitant accumulation of nonphosphorylated Cx43 signal occurred at sites of intercellular junctions. Functional recovery during reperfusion was associated with increased levels of phosphorylated Cx43. These observations suggest that uncoupling induced by ischemia is associated with dephosphorylation of Cx43, accumulation of nonphosphorylated Cx43 within gap junctions, and translocation of Cx43 from gap junctions into intracellular pools.

Carbon monoxide (CO) has been shown to be teratogenic in mice. High altitude hypoxia has also been shown to induce congenital vertebral anomalies in mice. The purpose of this study was to investigate the effect of maternal hypoxia owing to CO exposure and the production of congenital spinal deformities in the offspring. Sixty DBA-1J mice were bred using polygamous timed breeding methods. Pregnant females were exposed to 200, 400, or 600 ppm CO using a custom-designed gas blender system. Seven-hour exposures were performed on day 8.5, 9.5, or 10.5 of the 21-day gestation cycle. The neonates were euthanized at birth; the specimens were fixed, eviscerated, and radiographed. Congenital spinal deformities were observed (wedge, hemi, fused, and missing vertebrae; fused ribs) and were located in all regions of the spine. There was a statistically significant difference in the number of spinal deformities between all groups, with no defects in the controls and a 77% incidence at 600 ppm (p < 0.0001). There was no apparent correlation between the time of exposure and defect location. The most sensitive time of gestation was 9.5 days. We identified an animal model of congenital spinal deformities that compares favorably with the evidence of human congenital spinal deformities in cases of maternal exposure to CO and other gas and chemical fumes.

Background —Myocardial ischemia causes profound changes in both active membrane currents and passive electrical properties. Because these complex changes develop and progress concomitantly, it has not been possible to elucidate the relative contributions of any one component to arrhythmogenesis induced by acute ischemia. Cx43+/− mice express 50% of the normal level of connexin43 (Cx43), the major ventricular electrical coupling protein, but are otherwise identical to wild-type (Cx43+/+) mice. Comparison of arrhythmogenesis in Cx43+/− and +/+ mice can provide insights into the role of changes in electrical coupling as an independent variable in the complex setting of acute ischemia. Methods and Results —Acute ischemia was induced in isolated perfused mouse hearts by occlusion of the left anterior descending coronary artery. Spontaneous ventricular tachyarrhythmias (VT) occurred in more than twice as many Cx43+/− hearts than Cx43+/+ hearts. VT was induced in nearly 3 times as many Cx43+/− hearts. Multiple runs and prolonged runs of spontaneous VT were more frequent in Cx43+/− hearts. Onset of the first run of VT occurred significantly earlier in Cx43+/− hearts. Premature ventricular beats were also more frequent in Cx43+/− hearts. The size of the hypoperfused region was equivalent in both groups. Conclusions —Reduced expression of Cx43 accelerates the onset and increases the incidence, frequency, and duration of ventricular tachyarrhythmias after coronary artery occlusion. Thus diminished electrical coupling per se plays a critical role in arrhythmogenesis induced by acute ischemia.

We have characterized an apparently full-length cDNA corresponding to a rat mRNA, SE6C, previously identified by subtractive hybridization as being expressed predominantly in the striatal region of the brain. The SE6C mRNA encodes a 266 amino acid protein with significant similarity to members of the Ras-like GTP-binding protein family; thus, we have chosen the name Rhes, for Ras homolog enriched in striatum. The human homolog was found in a genomic sequence from human chromosome 22q13.1 and shares 95% identity with rat Rhes. Among the family of small G-proteins, Rhes shares 62% identity with Dexras1, a mouse dexamethasone-inducible Ras-like protein. Both Rhes and Dexras1 have substantially longer C-termini than other members of the Ras-like small G-protein family. Divergence between the C-terminal sequences of Rhes and Dexras1 suggests that, although their functions are probably similar, they have unique properties. Bacterially expressed Rhes binds GTP, suggesting that the protein indeed has GTPase functionality. Although Rhes was not induced by dexamethasone, its full expression is dependent upon thyroid hormone availability. Its accumulation is postnatal, consistent with the dependence upon thyroid hormone. It is noteworthy that most striatum-“specific” mRNAs characterized to date encode components of signal transduction cascades. J. Neurosci. Res. 57:782–788, 1999. © 1999 Wiley-Liss, Inc.

Close to 20% of the patients infected with the AIDS virus develops neurological deficit; eventhough HIV does not invade neurons. Consistently with the neurological deficit, HIV(+) subjects show abnormalities in brainstem auditory and visual evoked potentials (BSAEP and VEP) and in sleep patterns. The HIV-derived glycoprotein 120 has been postulated as a neurotoxic; therefore, it may be playing a crucial role in the generation of BSAEP and VEP, as well as in sleep disturbances. To study the role of the virus-derived proteins on the development of these electrophysiological signals' alterations, we have used the feline immunodeficiency virus (FIV)-derived gp120 and evaluated the changes in these electrophysiological signals. We employed 15 adult male Sprague-Dawley rats (250-350 g), chronically implanted for evoked potential and sleep recordings. Results showed that the i.c.v. administration of FIVgp120 (5 ng/10 microliter) produces changes in the latency of both cortical auditory evoked potentials (CAEPs) and VEPs and a decrease in both REM sleep and SWS. These data support the notion that FIVgp120 is neurotoxic to the central nervous system of cats and rats and that this protein suffices to cause electrophysiological alterations. In addition, it suggests that a similar effect may be occurring in humans as a result of HIVgp120's neurotoxic effects.

This review examines some of the recent advances made in the prevention and treatment of upper airway obstruction in infancy and childhood. In some instances, the advances are the result of experimental studies that corroborate or refute therapeutic notions that had been adopted prematurely. Studies performed in the past few years, for instance, have demonstrated that both systemic and local corticosteroid treatments are indeed effective in the treatment of viral croup. In contrast, other studies carried out in the same period raise doubts about the usefulness of these medications in the prevention of postextubation laryngeal edema. In other instances, the advances are the result of pioneering efforts to correct anatomical defects, usually congenital, that cause severe airway obstruction. Tracheal and laryngeal stenoses and craniofacial deformities, which only 5 years ago would have been palliated by tracheotomy, undergo now routine primary correction. Despite all these advances, upper airway obstruction remains an important source of morbidity and mortality in early childhood.

Clubfoot is a birth defect that may be related to muscle weakness or imbalance. The purpose of this study was to examine the relationships among muscle and tendon size and embryonic motility in a paralyzed chick embryo model of clubfoot and arthrogryposis. Decamethonium bromide, a neuromuscular blocking agent, was administered to a series of embryos in five dosage groups, producing a cohort of embryos with various degrees of paralysis and atrophy of tendons and muscle. Embryonic movement frequency was monitored, and after death in late gestation, the cross-sectional areas of the calf musculature and the gastrocnemius tendon proximal to the ankle were measured histologically. Significant correlations were found between embryonic motility and both muscle (r 2 = 0.52) and tendon (r 2 = 0.77) areas. In addition, a significant correlation (r 2 = 0.74) was found between muscle and tendon areas, suggesting that a measurement of one may be used to predict the other.

Fluorochrome labeling and microcomputed tomography were used to completely characterize the regional and age-related variations in bone growth in the distal femur of the young rabbit. Use of the microcomputed tomography system, in conjunction with the more routine fluorochrome labeling, allows the investigation of changes in shape that occur during development. The growth plate in the distal femur studied here is remarkable for several reasons. First, growth rates of as much as 700 microns/day were measured, a much higher rate than those typically measured in other species or in more mature animals. In addition, regional variations in bone growth rates of as much as 300 microns/day were identified in the 6-week-old rabbit. These variations resulted in the formation of a complex curvature in the growth plate, including four mammillary processes. Identifying the factors that regulate this type of regional variation may be especially useful in understanding the causes for angular deformities such as tibia vara or developmental dysplasias.

Mammalian evolution is believed to be male driven because the greater number of germ cell divisions per generation in males increases the opportunity for errors in DNA replication. Since the Y Chromosome (Chr) replicates exclusively in males, its genes should also evolve faster than X or autosomal genes. In addition, estimating the overall male-to-female mutation ratio (alpha m) is of great importance as a large alpha m implies that replication-independent mutagenic events play a relatively small role in evolution. A small alpha m suggests that the impact of these factors may, in fact, be significant. In order to address this problem, we have analyzed the rates of evolution in the homologous X-Y common SMCX/SMCY genes from three different species--mouse, human, and horse. The SMC genes were chosen because the X and Y copies are highly homologous, well conserved in evolution, and in all probability functionally interchangeable. Sequence comparisons and analysis of synonymous substitutions in approximately 1kb of the 5' coding region of the SMC genes reveal that the Y-linked copies are evolving approximately 1.8 times faster than their X homologs. The male-to-female mutation ratio alpha m was estimated to be 3. These data support the hypothesis that mammalian evolution is male driven. However, the ratio value is far smaller than suggested in earlier works, implying significance of replication-independent mutagenic events in evolution.

A derivation of the Dirac and Weyl equations is presented which does not assume a first-order time derivative but instead is based on the relativistic transformation of spinors in ordinary quantum mechanics. The Dirac and Weyl 4-currents, the transformation properties of the Dirac and Weyl spinors, and the Lorentz covariance of the resulting equations are established in the course of the derivation. On etablit les equations de Dirac et de Weyl sans supposer a priori que la derivee temporelle est du premier ordre; on se base plutot sur la transformation relativiste des spineurs en mecanique quantique ordinaire. On obtient par cette methode les quadricourants de Dirac et de Weyl, les proprietes de transformation des spineurs de Dirac et de Weyl, ainsi que la covariance de Lorentz des equations.

OBJECTIVE: Our purpose was to determine the risk of fetal mosaicism when placental mosaicism is found on chorionic villus sampling. STUDY DESIGN: We present a case of mosaic trisomy 22 detected on chorionic villus sampling and subsequently found in the fetus. A review of comprehensive chorionic villus sampling studies with emphasis on follow-up for fetal mosaicism was conducted. RESULTS: Among 13 studies reviewed, 469 cases of placental mosaicism are presented; fetal mosaicism was found in 50 (10.7%). Factors associated with fetal mosaicism are (1) mosaicism on mesenchymal core culture and (2) type of chromosome abnormality involved - specifically, marker chromosomes (26.7%) and common autosomal trisomies (19.0%). Amniocentesis predicted fetal genotype in 93% to 100% of cases of placental mosaicism, depending on the cell type in which mosaicism was diagnosed. CONCLUSIONS: Although mosaicism is usually confined to the placenta, the fetus is involved in about 10% cases. Patients should be counseled about this risk and the accuracy of follow-up amniocentesis. (AM J OBSTET GYNECOL 1996;174:850-5.)

We present a phylogeny of all booted eagles (38 extant and one extinct species) based on analysis of published sequences from seven loci. We find molecular support for five major clades within the booted eagles: Nisaetus (10 species), Spizaetus (4 species), Clanga (3 species), Hieraaetus (6 species) and Aquila (11 species), requiring generic changes for 14 taxa. Additionally, we recommend that the Long-crested Eagle (Lophaetus occipitalis) and the Black Eagle (Ictinaetus malaiensis) remain in their monotypic genera, due to their distinctive morphology. We apply the recently resurrected genus Clanga for the spotted eagles (previously Aquila spp.) to resolve the paraphyly of the genus Aquila such that the clade including the Booted Eagle (H. pennatus), Little Eagle (H. morphnoides), Pygmy Eagle (H. weiskei), Ayres’s Eagle (H. ayresii) and Wahlberg’s Eagle (H. wahlbergi) can remain in the genus Hieraaetus. The Rufous-bellied Eagle should be retained in the genus Lophotriorchis. For consistency in English names, we recommend that the term “hawk-eagles” be used only for the species in the genera Nisaetus and Spizaetus. We suggest following new or modified English names: Cassin’s Eagle (Aquila africana), Bonaparte’s Eagle (A. spilogaster), Ayres’s Eagle (Hieraaetus ayresii), and Black-and-chestnut Hawk-Eagle (Spizaetus isidori). Molecular phylogeny, morphology, Nisaetus, Spizaetus, Clanga, Hieraaetus, Aquila, Oroaetus, Spizastur, Lophotriorchis © 2017 Magnolia Press. Licensed under a Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0