卵巢恶性肿瘤二次剖腹探查术中行腹膜后淋巴结清除术的研究

目的　探讨卵巢恶性肿瘤腹膜后淋巴结清除术的最佳时机和临床价值。方法　回顾性分析了 5 0例二次剖腹探查术 (SLL)中行腹膜后淋巴结清除术的卵巢恶性肿瘤患者的临床资料。结果　患者中位数年龄 49岁 ,其 3年和 5年生存率分别为 72 %和 62 %。SLL阳性率为 40 % ( 2 0 / 5 0 ) ,其中临床分期 [国际妇产科联盟 (FIGO)标准 ]Ⅰ期SLL阳性率为 0 % ( 0 / 15 ) ,Ⅱ期和Ⅲ期分别为 40 %( 4/ 10 )、62 % ( 15 / 2 4) ,Ⅳ期为 1例中 1例。SLL阳性率与临床分期的期别呈正相关 ,其中Ⅰ～Ⅱ期( 16% ,4/ 2 5 )和Ⅲ～Ⅳ期 ( 64 % ,16/ 2 5 )患者SLL阳性率比较 ,差异有极显著性 (P <0 0 1)。腹膜后淋巴结转移率为 3 2 % ( 16/ 5 0 ) ,其中Ⅰ、Ⅱ、Ⅲ期分别为 0 % ( 0 / 15 )、2 0 % ( 2 / 10 )、5 4% ( 13 / 2 4) ,Ⅳ期为 1例中1例。SLL阳性患者中 ,4例 ( 8% )仅盆腹腔内有转移灶 ,淋巴结无转移 ;6例 ( 12 % )仅显微镜下淋巴结转移 ,而无盆腹腔转移灶。SLL中 ,行二次肿瘤细胞减灭术共 2 0例 ,其中术后 13例残留灶直径≤ 0 5cm ,7例残留灶直径 >0 5cm。中位数随访时间 44个月 ( 2 4～ 10 4个月 ) ,至随访截止日SLL阴性者 ( 3 0例 )均无肿瘤复发。结论　腹膜后淋巴结清除术在SLL术中进行比较合理 ,而且对降低SLL阴性患     

产后抑郁症患者血浆孤啡肽及5-羟色胺水平变化的意义

目的　探讨产后抑郁症患者血浆中孤啡肽及 5 羟色胺水平变化与产后抑郁症发病的关系。方法　采用放射免疫法测定 2 5例正常产妇 (对照组 )及 2 1例产后抑郁症患者 (抑郁症组 )血浆中孤啡肽及 5 羟色胺水平。结果　 (1)抑郁症组血浆孤啡肽水平为 (2 8 5± 5 8)ng/L ,对照组血浆孤啡肽水平为 (10 4± 3 7)ng/L。抑郁症组血浆孤啡肽水平显著高于正常组 ,两组比较 ,差异有极显著性 (P <0 0 1)。 (2 )抑郁症组血浆 5 羟色胺水平为 (1 0± 0 3) μmol/L ,对照组为 (1 4± 0 4 ) μmol/L。抑郁症组血浆 5 羟色胺水平低于对照组 ,两组比较 ,差异有显著性 (P <0 0 5 )。 (3)抑郁症组血浆孤啡肽水平与 5 羟色胺水平呈显著负相关 (r=- 0 5 71,P <0 0 5 )。结论　产后抑郁症患者血浆孤啡肽水平变化与产后抑郁症的发生密切相关。     

Effects of oxygen-induced lung damage on megakaryocytopoiesis and platelet homeostasis in a rat model

The association between lung injury and thrombocytopenia was investigated by comparing the megakaryocyte and platelet counts, and platelet activation using P-selectin as a marker, between the prepulmonary (right atrial) and postpulmonary (left atrial) blood in adult and neonatal (preterm and term) rats with and without hyperoxic lung injury. In the healthy controls, the postpulmonary blood had lower megakaryocyte count (prepulmonary versus postpulmonary: Preterm: 8.7[0.6] versus 3.9[0.3] per ml, p < 0.001; Term: 8.7[1.1] versus 2.6[0.4] per ml, p < 0.001; Adult: median [interquartile ranges]: 2.5[1.0, 5.0] versus 1.0[0, 3.0] per ml, p < 0.001), higher platelet count (prepulmonary versus postpulmonary: Preterm: 491.2[11.1] x 10(9)/L versus 595.1[10.2] x 10(9)/L, p < 0.001; Term: 472.5[19.9] x 10(9)/L versus 579.3[26.2] x 10(9)/L, p < 0.001; Adult: 513.9[31.5] x 10(9)/L versus 664.7[28.8] x 10(9)/L, p < 0.001), but similar P-selectin expression. In contrast, the lung-damaged animals did not show any such differences in either megakaryocyte or platelet count, but P-selectin expression was greater in the postpulmonary blood (prepulmonary versus postpulmonary: Preterm: 38.7[3.9] versus 56.4[4.9]% platelets, p = 0.02; Term: 40.9[2.0] versus 54.0[4.2]% platelets, p = 0.002; Adults: 30.0[3.6] versus 49.1[4.7]% platelets, p = 0.003). Peripheral platelet and intra-pulmonary megakaryocyte counts in the lung-damaged rats were significantly lower than those in their respective controls. Intra-pulmonary thrombi or platelet aggregation were detected in the lung-damaged rats but not in the controls. These findings showed that hyperoxic lung damage reduced circulating platelets through (1) failure of the lungs to retain and fragment megakaryocytes to release platelets, and (2) platelet activation leading to platelet aggregation, thrombi formation and platelet consumption. The magnitude of platelet reduction was physiologically significant, as demonstrated by higher counts of megakaryocyte colony forming units in the bone marrow culture of the animals in the hyperoxia group when compared with the controls.     

A requirement for anaerobically induced redox functions during aerobic growth of Escherichia coli with serine,glycine and leucine as carbon source

Escherichia coli strains with mutations in 3 genes coding for redox functions--torA, nuoM and glpC--are able to grow with pyruvate as carbon source, but are not able to use a combination of serine, glycine and leucine as carbon source, unlike the parent strain which uses either. All three mutants are able to produce and activate L-serine deaminase (L-SD) when grown in glucose minimal medium, and thus should be able to convert serine to pyruvate and grow on it. We suggest that activation of L-SD involves specific chemical reactions, perhaps building an Fe-S cluster. Mutant cells can carry out the necessary reaction to activate L-SD when grown in glucose minimal medium but apparently cannot do so when grown in SGL medium.     

Molecular cloning of the carboxylesterase gene and biochemical characterization of the encoded protein from Pseudomonas citronellolis ATCC 13674

A genomic library of Pseudomonas citronellolis ATCC 13674 was constructed and screened for esterase activity in Escherichia coli using tributyrin-containing medium. One positive transformant was isolated, and subsequent analyses of the plasmid by restriction mapping revealed a 4.1-kb DNA fragment potentially carrying an esterase gene. The deduced nucleotide sequence of the DNA was found to contain an open reading frame encoding carboxylesterase and designated estA. Amino acid sequence analysis of estA showed the serine conservative motif, GDSAG, located between residues 208 and 212. Together with Ser, residues 310 and 334 corresponding to aspartic acid and histidine, respectively, comprised the catalytic triad. With the aid of immobilized metal ion affinity chromatography, the carboxylesterase fused with poly His at its C-terminus was purified and shown to be strongly inhibited by the tryptophan modifier and mercuric ion, indicating the important role of conservative Trp (189) and cysteine (152 and/or 183) residues in maintaining the structural integrity of the protein. Further analyses showed that the carboxylesterase functioned optimally at 37-40 degrees C with pH ranging between 8 and 9 and displayed a broad substrate spectrum. The protein exhibited greater preference toward short-chain (C2-C4) than medium- and long-chain fatty acids. Higher substrate specificity on para-nitrophenol butyrate was observed in comparison with para-nitrophenol acetate as indicated by the higher kcat/Km value of the former.     

Development of a postnatal 3-day-old rat model of mild hypoxic-ischemic brain injury

Improvements in both obstetric and paediatric care have been responsible for a continuing reduction in mortality in extremely premature infants. However, higher survival rates have been at the expense of more long-term neurological damage. Various animal models have been developed to study the effect of hypoxic-ischemic insults on the brain. However, established models like the postnatal day 7 rat model represent damage found in term infants rather than in preterm infants of 24-28 weeks' gestation, and produce a severe form of injury resulting in high mortality rates. In this study we developed a reliable model of minor hypoxic-ischemic brain injury in postnatal day 3 rats. At this maturity, the pattern of damage represents that expected in a preterm infant suffering a non-lethal perinatal insult.We found that minor changes in duration of insult and both temperature and humidity produced wide fluctuations in the degree of injury observed. By maintaining strict control over experimental conditions including duration of insult, temperature and humidity, we produced a reliable model of minor injury primarily affecting all five areas of the cerebral cortex, and also the thalamus (area 7) and basal ganglia (area 8). Differences were significant compared to normal controls and sham-operated animals (p<0.05). These areas represent the primary motor, insular, visual and temporal cortices. The overall mortality rate in this study was 12.3%.     

Ultrastructural localization of serotonin 2A and N-methyl-D-aspartate receptors in somata and dendrites of single neurons within rat dorsal motor nucleus of the vagus

Both glutamate and serotonin are potent modulators of autonomic functions involving the nucleus of the solitary tract (NTS) and the dorsal motor nucleus of the vagus (DMNV) at the level of the area postrema. Moreover, many of the dendrites in this NTS region express both N-methyl-D-aspartate (NMDA) and serotonin (5HT) 2A receptors, and some of these dendrites may arise from the adjacent DMNV. Thus, single neurons in DMNV may also express both receptors. To test this hypothesis, we used electron microscopic immunocytochemistry for dual localization of the essential R1 subunit of the NMDA receptor (NR1) and the 5HT2A receptor in rat intermediate DMNV, a region serving mainly gastrointestinal functions. Gold particles representing NR1 and peroxidase reaction product for 5HT2A receptors were seen in the cytoplasm, as well as on distinct segments of the plasma membrane of many dendrites. Of the NR1-labeled dendrites, 31% (254/814) also contained 5HT2A immunoreactivity; among the 5HT2A-labeled dendrites, 52% (254/485) expressed NR1. The 5HT2A labeling was also present in numerous small unmyelinated axons, axon terminals, and glial processes. These profiles were largely without NR1 immunoreactivity, although NR1 was detected in some of the dendrites postsynaptic to 5HT2A-labeled terminals. Our results suggest that calcium entry through NMDA channels and 5HT2A receptor activation may dramatically affect postsynaptic excitability of single neurons in the DMNV. In addition, the findings also indicate that the 5HT2A receptor is strategically positioned for involvement in modulation of the presynaptic release of neurotransmitters affecting the postsynaptic activity of DMNV neurons responsive to NMDA activation.     

Molecular mapping of the origin of postnatal spinal cord ependymal cells: evidence that adult ependymal cells are derived from Nkx6.1+ ventral neural progenitor cells

Recent studies have suggested that the ependymal cells lining the central canal of postnatal spinal cord possess certain properties of neural stem cells. However, the embryonic origin and developmental potential of the postnatal spinal cord ependymal cells remain to be defined. In this report, we investigated the developmental origin of postnatal spinal ependymal cells by studying the dynamic expression of several neural progenitor genes that are initially expressed in distinct domains of neuroepithelium in young embryos. At later stages of development, as the ventricular zone of the embryonic spinal cord is reduced, expression of Nkx6.1 progenitor gene is constantly detected in ependymal cells throughout chick and mouse development. Expression of other neural progenitor genes that lie either dorsal or ventral to the Nkx6.1+ domain is gradually decreased and eventually disappeared. These results suggest that the remaining neuroepithelial cells at later stages of animal life are derived from the Nkx6.1+ ventral neuroepithelial cells. Expression of Nkx6.1 in the remaining neuroepithelium is closely associated with, and regulated by, Shh expression in the floor plate. In addition, we suggested that the Nkx6.1+ ependymal cells in adult mouse spinal cords may retain the proliferative property of neural stem cells.     

Mapping of rat brain using the Synuclein-1 monoclonal antibody reveals somatodendritic expression of alpha-synuclein in populations of neurons homologous to those vulnerable to Lewy body formation in human synucleopathies

The neuronal protein alpha-synuclein has been implicated in the pathogenesis of Parkinson disease and other neurodegenerative diseases. Although many studies report that alpha-synuclein expression is restricted to neuronal presynaptic terminals, this protein aggregates in Lewy bodies in somata that are typically distant from their axon terminals. Few studies have addressed this paradox and there has been no compelling explanation proposed for the apparent discrepancy between the locus of neuronal alpha-synuclein expression and the loci of Lewy bodies in the majority of Parkinson disease cases. We explored this issue by extensively characterizing the monoclonal antibody Synuclein-1 (Syn-1) and using this highly selective antibody to map the distribution of alpha-synuclein throughout rat brain and in human substantia nigra (SN). Additionally, alpha-synuclein expression in rat SN detected by 2 polyclonal antibodies against alpha-synuclein was compared with that detected by the Syn-1 antibody. In contrast with many previous reports, alpha-synuclein was detected by Syn-1 in neuronal somata and dendrites in restricted brain regions, as well as more ubiquitously in axons and terminals. The strongest alpha-synuclein neuronal expression in rat was found in brainstem and cortical regions that are homologous to regions prone to Lewy body formation in humans. The Syn-1 antibody labeled abundant somatodendritic alpha-synuclein in both rat and human SN, a major locus of Lewy body formation and neurodegeneration in Parkinson disease. By contrast, very few immunoreactive somata in the rat SN were labeled by the 2 polyclonal antibodies. We explore possible explanations for the differences in conflicting reports of patterns of alpha-synuclein expression in brain, including differences among antibodies.     

Improvement of muscle healing through enhancement of muscle regeneration and prevention of fibrosis

Skeletal muscle is able to repair itself through regeneration. However, an injured muscle often does not fully recover its strength because complete muscle regeneration is hindered by the development of fibrosis. Biological approaches to improve muscle healing by enhancing muscle regeneration and reducing the formation of fibrosis are being investigated. Previously, we have determined that insulin-like growth factor-1 (IGF-1) can improve muscle regeneration in injured muscle. We also have investigated the use of an antifibrotic agent, decorin, to reduce muscle fibrosis following injury. The aim of this study was to combine these two therapeutic methods in an attempt to develop a new biological approach to promote efficient healing and recovery of strength after muscle injuries. Our findings indicate that further improvement in the healing of muscle lacerations is attained histologically by the combined administration of IGF-1 to enhance muscle regeneration and decorin to reduce the formation of fibrosis. This improvement was not associated with improved responses to physiological testing, at least at the time-points tested in this study.