Tissue Doppler gated (TDOG) dynamic three-dimensional ultrasound imaging of the fetal heart.

Dynamic three-dimensional (3D) ultrasound imaging of the fetal heart is difficult due to the absence of an electrocardiogram (ECG) signal for synchronization between loops. In this study we introduce tissue Doppler gating (TDOG), a technique in which tissue Doppler data are used to calculate a gating signal. We have applied this cardiac gating method to dynamic 3D reconstructions of the heart of eight fetuses aged 20-24 weeks.The gating signal was derived from the amplitude and frequency contents of the tissue Doppler signal. We used this signal as a replacement for ECG in a 3D-volume reconstruction and visualization, utilizing techniques established in ECG-gated 3D echocardiography.The reliability of the TDOG signal for fetal cardiac cycle detection was experimentally investigated. Simultaneous recordings of tissue Doppler of the heart and continuous wave (CW) spectral Doppler of the umbilical artery (UA) were performed using two independent ultrasound systems, and the TDOG signal from one system was compared to the Doppler spectrum data from the other system. Each recording consisted of a two-dimensional (2D) sector scan, transabdominally and slowly tilted by the operator, covering the fetal heart over approximately 40 cardiac cycles. The total angle of the sweep was estimated by recording a separate loop through the center of the heart, in the elevation direction of the sweep.3D reconstruction and visualization were performed with the EchoPAC-3D software (GE Medical Systems). The 3D data were visualized by showing simultaneous cineloops of three 2D slices, as well as by volume projections running in cineloop.Synchronization of B-mode cineloops with the TDOG signal proved to be sufficiently accurate for reconstruction of high-quality dynamic 3D data. We show one example of a B-mode recording with a frame rate of 96 frames/s over 20 seconds. The reconstruction consists of 31 volumes, each with 49 tilted frames. With the fetal heart positioned 5-8 cm from the transducer, the sampling distances were approximately 0.15 mm in the beam direction, 0.33 degrees approximately 0.37 mm azimuth and 0.45 degrees approximately 0.51 mm elevation. From this single dataset we were able to generate a complete set of classical 2D views (such as four-chamber, three-vessel and short-axis views as well as those of the ascending aorta, aortic and ductal arches and inferior and superior venae cavae) with high image quality adequate for clinical use.     

人体液中喷布洛尔及其代谢物的GC/MS分析

用气相色谱一质谱联用(GC-MSD)系统分析方法检出了人尿中喷布洛尔的6个羟化代谢物,用Scp-Pak柱提取的方法检出了人血浆中的原型药物。并从分子结构上对此药物的代谢途径进行了研究。尿中提取和血中提取的回收率分别为90.83.%和85.88%,Gc-MSD的检测限为5pg。本方法适用于运动员兴奋剂的系统检查。     

An examination of the relationships among three outcome scales in schizophrenia.

The functioning of 94 schizophrenic subjects was rated using the Global Assessment Scale, the Strauss and Carpenter Outcome Scale, and the Role Functioning Scale. The convergent validity among the scales was quite modest and highly variable. Solid empirical convergence only occurred when two of the scales each measured social and vocational dimensions of functioning. It is argued that these findings strongly illustrate the need for conceptual and operational consensus in this area. The findings also support the notion of outcome in schizophrenia as a set of distinct, yet linked, dimensions. Other implications of the findings for the definition and measurement of outcome in schizophrenia when using global and multidimensional scales are discussed.     

Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability

X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene. Disease-associated alleles (37-66 CAGs) change in length when transmitted from parents to offspring, with a significantly greater tendency to shift size when inherited paternally. As transgenic mice carrying human AR cDNAs with 45 and 66 CAG repeats do not display repeat instability, we attempted to model trinucleotide repeat instability by generating transgenic mice with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions in their genomic context. Studies of independent lines of AR YAC transgenic mice with CAG 45 alleles reveal intergenerational instability at an overall rate of approximately 10%. We also find that the 45 CAG repeat tracts are significantly more unstable with maternal transmission and as the transmitting mother ages. Of all the CAG/CTG repeat transgenic mice produced to date the AR YAC CAG 45 mice are unstable with the smallest trinucleotide repeat mutations, suggesting that the length threshold for repeat instability in the mouse may be lowered by including the appropriate flanking human DNA sequences. By sequence-tagged site content analysis and long range mapping we determined that one unstable transgenic line has integrated an approximately 70 kb segment of the AR locus due to fragmentation of the AR YAC. Identification of the cis - acting elements that permit CAG tract instability and the trans -acting factors that modulate repeat instability in the AR YAC CAG 45 mice may provide insights into the molecular basis of trinucleotide repeat instability in humans.      

Lysine 322 in the human IgG3 C(H)2 domain is crucial for antibody dependent complement activation

The classical complement activation cascade of the immune system is initiated by multivalent binding of its first component, C1q, to the Fc region of immunoglobulins in immune complexes. The C1q binding site on mouse IgG2b has been shown to contain the amino acids Glu 318, Lys 320 and Lys 322 in the C(H)2 domain (Duncan, A.R., Winter, G.,1988. The binding site for C1q on IgG. Nature 322 738-740). Identical or closely related motifs are found on all IgGs in all species, and the binding site has therefore been thought to be universal. However, the results from another study indicate that the site is different in human IgG1 molecules (Morgan, A., Jones, N.D., Nesbitt, A.M., et al., 1995. The N-terminal end of the C(H)2 domain of chimeric human IgG1 anti-HLA-DR is necessary for C1q, Fc gamma RI and Fc gamma RIII binding. Immunology 86 319-324). To determine the site(s) responsible for complement activation in anti-NIP-mouse/human IgG3 antibodies, we have mutated amino acids Lys 276, Tyr 278, Asp 280, Glu 318, Lys 320 and Lys 322 in two beta-strands in the C(H)2 domains of human IgG3. In addition, we mutated the Glu 333, which resides in close proximity to the postulated C1q-binding site of mouse IgG2b, as well as Leu 235 in the lower hinge region. All mutants were tested in Antibody Dependent Complement Mediated Lysis (ADCML)(4) assays, where the antigen concentration on target cells was varied and human serum was complement source. Only the mutants that lacked the positively charged side chain of lysine in position 322 showed strong reduction in ADCML, particularly at low antigen density on target cells. Alanine scanning of positions 318 and 320 did not affect ADCML, contrary to what was observed for mouse IgG2b. Neither did a leucine to glutamic acid mutation in position 235 have the effect that has been reported for human IgG1. These results suggest that the complement binding site on human IgG3 molecules is different from that found on mouse IgG2b, and possibly on human IgG1 as well. Thus the contact site may not be conserved.     

Presence of the AZF region in a female with an idic(Y)(q11)

In a child with some features of Turner's syndrome, gonosomal mosaicism with an isodicentric nonfluorescent (idic)Y chromosome was detected (mos 45,X/47,X,idic(Y)(q11),idic(Y)(11)/46,X,idic(Y)(q11)). Histopathological examination showed streak gonads with some evidence of ovarian stroma and no sign of gonadoblastoma. Polymerase chain reaction (PCR) analysis in blood lymphocytes and gonadal tissues using primers of seven loci along the Y chromosome, including the sex determined region (SRY), azoospermia factor region (AZF) and the deleted in azoospermia ( DAZ ) gene was positive for all loci tested, confirming the isodicentric character of the Y chromosome and indicating the presence of the AZF region. It is remarkable that the existence of spermatogenesis controlling genes does not play an important role in gonadal development and differentiation in a phenotypic female with some Turner stigmata. The data presented here are briefly discussed with previously-described patients.