Tolerance and immunity following in utero transplantation of allogeneic fetal liver cells: the cytokine shift

Although in utero transplantation (IUT) has resulted in donor-specific tolerance to posnatal solid organ transplantation, the mechanisms of this tolerance remain poorly understood. Our recent findings demonstrate that under specific conditions prenatal injection of allogeneic cells may lead to allosensitization instead of tolerance. These laboratory observations were supported by clinical findings as well, and therefore suggested that, depending on the conditions of prenatal transplantation, tolerance or immunity may develop. The present study explored the role of CD4 cells, cytokines, and I-E superantigen in developing tolerance vs. immunity after in utero transplantation. Sixteen animals survived IUT (40-60% survival rate) and were free from any signs of graft-versus-host disease (GVHD). Mice were considered tolerant when their antidonor and antihost CTL responses were similar, sensitized when antidonor responses were significantly higher than antihost and anti-third-party responses, and nontolerant when antidonor responses in transplanted and control mice were similar. The TH1 --> TH2 shift was associated with tolerance and TH2 --> TH1 shift with allosensitization. Our results showed that tolerant BALB/c (H-2d, I-E+) --> CS7BL/6 (H-2b, I-E-) (2/7) mice showed higher IL-4 (p < 0.05) in antidonor MLR, and partial deletion of recipient I-E-reactive T cells (CD3Vbeta11) (p < 0.045). On the other hand, nontolerant animals (5/7) demonstrated high production of IFN-gamma (p < 0.05) without deletion of CD3Vbeta11 T cells. In C57CBL/6 (H-2b, I-E-) --> C3H (H-2k, I-E+) mice CD3Vbeta11 T cells do not play any role in tolerance induction because they are deleted in the C3H background. Tolerant mice (4/9) showed an overproduction of IL-4 (p < 0.05) in antidonor MLR whereas allosensitized animals (5/9) demonstrated high level of IFN-gamma (p < 0.05). Suppressor cells seem to play no role in tolerant C57BL/6 --> C3H as demonstrated by suppressor assay. Hence, a shift from TH1 --> TH2 or TH2 --> TH1 cytokines may determine whether tolerance or immunity develops.     

Determining the probability of future smoking among adolescents

Aims. To determine whether the probability of future current established smoking among adolescents is related to both previous smoking experience and cognitions regarding future smoking. Design, setting and participants. The analyses used two principal datasets: (1) a US longitudinal sample of 7960 adolescents 12-18 years old in 1989 reinterviewed at 15-22 years in 1993, (2) a California longitudinal sample of 3376 adolescents 12-17 years old in 1993 reinterviewed at 15-20 years in 1996. Measures. Previous smoking experience was categorized as never smoked, puffed, non-recent or recent experimenting, and non-recent or current established smoking (≥ 100 cigarettes in life-time). Smoking intentions and efficacy expectations were used to classify adolescents as having low- or high-risk cognitions. Findings. High-risk cognitions (HRCs) increased the probability of future current established smoking (FCES) within each level of previous smoking experience over low-risk cognitions (LRCs); the probability of FCES for those with LRCs was about the same as those in the previous experience group with HRCs. In the US sample, the 4-year probability of FCES ranged from 5.6% for committed never smokers (with LRCs) to 83.0% for current established smokers with HRCs. Development of HRCs among middle-school never smokers occurred rapidly through age 14 years. However, current established smoking did not increase until age 14 years and stabilized by age 19 years. Where sample size was sufficient, these findings were validated in the California sample. Conclusions. Effective prevention programs should aim to convert HRCs to LRCs regardless of past behavior, particularly among middle-school never smokers and high-school experimenters.     

Mechanism of IL-1 induced inhibition of protein synthesis in skeletal muscle

Chronic interleukin (IL)-1 administration is associated with negative nitrogen balance and the loss of lean body mass. To elucidate the molecular mechanism(s) by which IL-1 modulates protein metabolism in muscle, we investigated the effects of chronic (6 day) IL-1alpha infusion on protein synthesis in Individual muscles (gastrocnemius, soleus, heart) compared with saline-infused control rats. IL-1 significantly decreased muscle weight, protein content, and the rate of protein synthesis in gastrocnemius (fast-twitch muscle). IL-1 had no effect on these parameters in the heart, whereas only the rate of protein synthesis was reduced in soleus (slow-twitch muscle). The reduction in gastrocnemius protein synthesis was not the result of a decrease in total RNA content, but was associated with a diminished translational efficiency. The diminished translational efficiency correlated with a 40% reduction in the epsilon-subunit of eukaryotic initiation factor 2B (elF2Bepsilon) in gastrocnemius from IL-1 -treated animals. However, the content of the alpha-subunit of elF2 (elF2alpha) was unaffected. In contrast, the elF2alpha content in heart was increased by IL-1, although elF2Bepsilon levels were unchanged. Reductions in skeletal muscle protein synthesis were not associated with a concomitant reduction in circulating or tissue content of insulin-like growth factor I. In summary, the IL-1-induced decrease in gastrocnemius protein synthesis appears to be regulated at the level of RNA translation via a reduction in elF2Bepsilon. These findings support a regulatory role for IL-1 as a mediator of muscle protein synthesis and the alterations in body composition observed in catabolic states where this cytokine is overexpressed.     

SB-203207 and SB-203208, two novel isoleucyl tRNA synthetase inhibitors from a Streptomyces sp. II. Structure determination

Two novel isoleucyl tRNA synthetase inhibitors, SB-203207 and SB-203208 have been isolated from a Streptomyces sp. and found to be structurally related to altemicidin. Structures of SB-203207 and SB-203208 have been deduced by a combination of spectroscopic techniques, derivatisation, hydrolysis studies and found to be 4-(aminocarbonyl)-7-[[(2-amino-3-methylpentanoyl)aminosul phonyl]acetamido]-2,4a,5,6,7,7a-hexahydro-6-hydroxy-2-methyl-1H-2- pyrindine-7-carboxylic acid (1) and 4-(aminocarbonyl)-7-[[(2-amino-3-methyl pentanoyl)-aminosulphonyl]acetamido]-2,4a,5,6,7,7a-hexahydro-6-(2- amino-3-phenylbutanoyl oxy)-2-methyl-1H-2-pyrindine-7-carboxylic acid (2), respectively.     

基因芯片技术在脑损伤研究中的应用

基因芯片技术是最近发展起来的新兴分子生物学技术,它的并行处理特点使大规模研究脑损伤后的基因改变成为切实可能。本文综述了新近用基因芯片技术在脑损伤后基因表达时序性改变及基因表达谱分析等研究中的应用。     

Isthmic spondylolysis of the lumbar spine: MR imaging at 1.5 T

The appearance on magnetic resonance (MR) images of the normal pars interarticularis in 13 patients was reviewed and contrasted with that of the pars in eight patients with spondylolysis. The pars defect usually had an intermediate signal intensity with all pulse sequences; however, this intensity was somewhat variable depending on the exact ratio of cartilage, fat, and fluid within each bone defect. The pars defect was best seen with spin-echo 600/20 (repetition time msec/echo time msec) images. In three cases, out-of-phase images showed the spondylolysis best, because of extension of fat to the borders of the defect. The sagittal view allowed one to separate spondylolysis from the joint space of posterior facets since the orientation of the defects is perpendicular to the facets; thus, a common pitfall encountered with cross-sectional axial imaging techniques is avoided. MR imaging poorly delineated bone fragments around the defect, which may produce nerve root impingement, but revealed other numerous complications that occur with spondylolysis, including spondylolisthesis and herniation of the disk above.     

Transabdominal versus endovaginal pelvic sonography: prospective study

Transabdominal and endovaginal pelvic sonograms were obtained in 108 nonpregnant patients referred for pelvic sonography. The studies were independently obtained by two radiologists and interpreted on the basis of identical clinical information. The sonograms were then compared for anatomic detail and abnormalities. A determination was made about which examination, if either, was superior. Follow-up was performed through a review of the medical records and follow-up studies. Overall, the endovaginal study was judged superior in 65 cases (60.2%), equal in 39 (36.1%), and inferior in four (3.7%). The authors conclude that the endovaginal examination can effectively replace the transabdominal examination as the initial approach for routine pelvic sonography.     

从平贝母茎叶中分离的平贝啶甙的结构

本文报道自平贝母(Fritillaria ussuriensis Maxim)的地上茎叶中分得一种新的甾体生物碱甙,定名为平贝啶甙(pingbeidinoside),mp 242～243.2℃[a]_D²⁵+6.9°(c 0.145,MeOH)。经IR,MS,¹HNMR和¹³CNMR谱解析,推定其结构为3β,16α,20-三羟基-Δ⁵-22,26-缩亚胺胆甾烷-25-O-α-D-葡萄糖甙。