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。     

Quality of life of pancreatic transplant recipients.

OBJECTIVE--To comprehensively assess and compare pancreas/kidney transplant recipients' quality of life. RESEARCH DESIGN AND METHODS--This quasi-experimental comparative study of 31 successful and 13 failed pancreas transplant recipients collected data from persons who had received pancreas and kidney transplants > or = 6 mo prior at a university tertiary care center. Physical and social function, symptoms, mental state, and sense of well-being of the recipients were assessed. RESULTS--Groups did not differ significantly regarding age, gender, marital status, onset or length of diabetes, comorbidity, type of prior dialysis, current kidney function, length of time since transplant, physical activity, symptom burden, emotional state, feelings of well-being, and present quality of life and health. A significant time by group interaction occurred for quality of life (P = 0.0013) and health (P = 0.0001). The successful group indicated that both quality of life and health were significantly better than in the past, and continued improvement was expected. The unsuccessful group did not have this perception. Members of the failed group were significantly more satisfied with their social support. The unsuccessful group's major concerns related to diabetes, not immunosuppression. CONCLUSIONS--Recipients of successful pancreas transplants perceived their improvement in health and quality of life to be significantly greater than the unsuccessful recipients.     

Aortic root dilatation may alter the dimensions of the valve leaflets

Objective: Valve-sparing surgery can be used in patients with dilated aortic roots and aortic insufficiency (AI) but has not become a common practice, in part because the spared valve may be incompetent. Our goal was to study how the dimensions of the aortic root and leaflets have changed in such patients. Methods: Fourteen patients with dilated aortic root and AI were examined by transesophageal echocardiography. The annulus diameter, sinotubular junction (STJ) diameter, sinus height, leaflet free-edge length, and leaflet height were measured. Correlations among these dimensions and with the AI grades were explored. Measurements were also made in 19 normal human aortic valves from silicone molds. Results: There was no evident change in the average diameter of the annulus between the normal valves and those in the dilated aortic roots. The STJ diameter was obviously increased in the dilated aortic roots; the aortic sinuses also appeared to be taller and the leaflets larger than normal. The leaflet free-edge length, the leaflet height, and the sinus height were found to increase with the dilated STJ diameter. The degree of AI was not found to correlate well with any of the dimensions measured. Conclusions: The dimensions of the leaflets may change parallel to aortic root dilatation with AI. Therefore, during valve sparing, it may be necessary to correct both the dilatation of the root and the leaflet free-edge length to achieve a competent valve.     

Modulation of cutaneous reflexes in arm muscles during walking: further evidence of similar control mechanisms for rhythmic human arm and leg movements

Stimulation of cutaneous nerves innervating the hand evokes prominent reflexes in many arm muscles during arm cycling. We hypothesized that the mechanisms controlling reflex modulation during the rhythmic arm swing of walking would be similar to that documented during arm cycling. Thus, we expected cutaneous reflexes to be modulated by position in the walking cycle (phase dependence) and be different when walking compared to contraction while standing (task dependence). Subjects performed static postures similar to those occurring during walking and also walked on a treadmill while the superficial radial nerve was electrically stimulated pseudorandomly throughout the step cycle. EMG was recorded bilaterally from upper limb muscles and kinematic recordings were obtained from the elbow and shoulder joints. Step cycle information was obtained from force-sensing insoles. Analysis was conducted after averaging contingent upon the occurrence of stimulation in the step cycle. Phase-dependent modulation of cutaneous reflexes at early (~50–80 ms) and middle (~80–120 ms) latencies was observed. Coordinated bilateral reflexes were seen in posterior deltoid and triceps brachii muscles. Task dependency was seen in that reflex amplitude was only correlated with background EMG during static contraction (75% of comparisons for both early and middle latency reflexes). During walking, no significant relationship between reflex amplitude and background EMG level was found. The results show that cutaneous reflex modulation during rhythmic upper limb movement is similar to that seen during arm cycling and to that observed in leg muscles during locomotion. These results add to the evidence that, during cyclical movements of the arms and legs, similar neural mechanisms observed only during movement (e.g. central pattern generators) control reflex output. Electronic Publication     

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.      

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.     

Modulation of human cutaneous reflexes during rhythmic cyclical arm movement

The organization and pattern of cutaneous reflex modulation is unknown during rhythmic cyclical movements of the human upper limbs. On the assumption that these cyclic arm movements are central pattern generator (CPG) driven as has been suggested for leg movements such as walking, we hypothesized that cutaneous reflex amplitude would be independent of electromyographic (EMG) muscle activation level during rhythmic arm movement (phase-dependent modulation, as is often the case in the lower limb during locomotion). EMG was recorded from eight muscles crossing the human shoulder, elbow, and wrist joints while whole arm rhythmic cyclical movements were performed. Cutaneous reflexes were evoked with trains of electrical stimulation delivered at non-noxious intensities (approximately 2 x threshold for radiating paresthesia) to the superficial radial nerve innervating the lateral portion of the back of the hand. Phasic bursts of rhythmic muscle activity occurred throughout the movement cycle. Rhythmic EMG and kinematic patterns were similar to what has been seen in the human lower limb during locomotor activities such as cycling or walking: there were extensive periods of reciprocal activation of antagonist muscles. For most muscles, cutaneous reflexes were modulated with the movement cycle and were strongly correlated with the movement-related background EMG amplitude. It is concluded that cutaneous reflexes are primarily modulated by the background muscle activity during rhythmic human upper limb movements, with only some muscles showing phase-dependent modulation.     

In vitro studies on human IgD. II. IgD-secreting cells preferentially elaborate IgD, lambda molecules

The "IgD paradox" describes the unexpected finding that, despite a predominance of kappa (kappa) light (L) chains on the surface of IgD+ human B cells, the majority of monoclonal IgD proteins are of lambda (lambda) type. This potentially informative phenomenon appears to be based on a preferential association between delta (delta) heavy (H) and lambda L chains of IgD-secreting cells. The current studies analyze the phenomenon in vitro. Initial assays on tonsil "spent" supernatants showed that the higher IgD-"externalizing" cultures displayed progressively elevated IgD, lambda/kappa ratios due to parallel shifts in total IgD and IgD, lambda while IgD, kappa remained stable. The cells of the same higher-IgD cultures demonstrated that individual IgD-containing cells had a predominance of lambda chains in contrast to IgM-containing cells of the same cultures using fluorochrome-antibody double staining. Certain tonsil culture IgD-containing cells remarkably appeared to have exclusively lambda chain. These same tonsils show evidence of IgD secretion (Litwin, S. D. and Zehr, B. D., Eur. J. Immunol. 1987. 17:483); thus, these data align preferential delta-lambda chain association with IgD-secreting normal tonsil B cells in vitro and emphasize the usefulness of IgD, lambda/kappa ratio in monitoring IgD secretion. In another approach the relationship between the cellular location of IgD and the preferential delta-lambda chain association was studied using Triton X-114-partitioned cell lysates. IgD, lambda/kappa ratios were one or less in the detergent phase (membrane-enriched fraction) consistent with expected IgD, kappa predominance in membrane IgD. In contrast, the aqueous phase (intracellular-enriched fraction) of IgD-secreting cultures had 2-4 times higher supernatant IgD, lambda/kappa ratios. The restriction of high IgD, lambda/kappa ratios to intracellular fractions and supernatants of IgD-secreting cultured cells parallels the predicted distribution of secretory IgD. In sera studies, the correlation between total IgD and IgD, lambda/kappa ratio values was consistent with secreted sera IgD showing preferential lambda chain expression. It was concluded that the phenomenon of delta-lambda chain preferential association is expressed in vitro as well as in vivo; a property of normal, nonmalignant human IgD-secreting B cells; and closely related to the secretory form of IgD. In certain cultures, the delta-lambda chain preference was so striking as to imply limited heterogeneity of the IgD immune response.