Three new taxane diterpenoids from seeds of the Chinese yew, Taxus yunnanensis and T. chinensis var. mairei

Three new taxane diterpenoids were isolated from the seeds of the Chinese yew, Taxus yunnanensis Cheng et L. K. Fu and T. chinensis var. mairei Cheng et L. K. Fu. The structures were established as 1beta,10beta-dihydroxy-9alpha,13alpha-diacetoxy-5alpha-(3'-dimethylamino-3'-phenyl)-propionyloxytaxa-4(20),11-diene, 5alpha-hydroxy-9alpha,100,13alpha-triacetoxy-11(15-->1)abeotaxa-4(20),11-di-ene, and 5alpha,13alpha-dihydroxy-9alpha,10beta-diacetoxy-11 (15-->1 )abeo-taxa-4(20),11-diene on the basis of 1D, 2D NMR, and mass spectral analysis.     

大肠癌组织中端粒酶活性的研究

目的研究大肠癌组织及相应癌旁组织中的端粒酶活性,探讨其作为肠癌肿瘤标记物的可能性。方法采用ＴＲＡＰ方法研究了４０例大肠组织（包括３７例大肠癌,３例良性大肠疾病）和２０例相应癌旁上皮组织中的端粒酶活性表达。结果２０例癌旁上皮和３例良性疾病组织中,端粒酶活性表达均为阴性;而３７例大肠癌组织中,３５例显示端粒酶活性表达为阳性,阳性率为９４．６％。结论端粒酶是特异性较强的恶性肿瘤基因标志,有可能成为大肠癌早期诊断和治疗的理想标志物     

Longitudinal study of earthquake-related PTSD in a randomly selected community sample in north China

OBJECTIVE: This study longitudinally described rates of posttraumatic stress disorder (PTSD) in two groups with different levels of severity of exposure to an earthquake in North China. The effects of diagnostic criteria on the frequency of detected PTSD were also examined. METHOD: Subjects were randomly sampled in two villages at different distances from the earthquake epicenter. A total of 181 and 157 subjects were assessed at 3 months and 9 months after the earthquake, respectively, for PTSD by using both DSM-IV and DSM-III-R criteria. The brief version of the World Health Organization Quality of Life Assessment and three subscales of the SCL-90-R were also administered at both assessment points. RESULTS: The village with a higher level of initial exposure to the earthquake and a higher level of postearthquake support had a lower frequency of PTSD than the village with a lower level of initial exposure and less postearthquake support. The rate of onset of DSM-IV PTSD within 9 months for the two villages was 19.8% and 30.3%, respectively. In both villages, the rate of onset of earthquake-related PTSD within 9 months was 24.2% by using DSM-IV criteria and 41.4% by using DSM-III-R criteria. The introduction in DSM-IV of a criterion requiring clinically significant distress or impairment in functioning for a diagnosis of PTSD was a major contributor to the lower rate of DSM-IV PTSD. CONCLUSIONS: PTSD may be as prevalent and persistent in disaster victims in China as in those elsewhere. Prompt and effective postdisaster intervention could mitigate the impact of initial exposure and reduce the probability of PTSD occurrence. Caution should be used in comparing rates of postdisaster PTSD identified by using different diagnostic criteria.     

Caspase inhibitors reduce neuronal injury after focal but not global cerebral ischemia in rats

BACKGROUND AND PURPOSE: Studies show that blocking the activation of caspases by the caspase inhibitors z-VAD.FMK and z-DEVD.FMK can reduce ischemic neuronal injury after cerebral ischemia. Because the severity of ischemia was mild in some studies, we tested the efficacy of these caspase inhibitors on moderately severe but transient forebrain and focal ischemic insults in the rat. METHODS: Various regimens of z-VAD, z-DEVD, and control DMSO were given to rats subjected to either 4-vessel occlusion ischemia (4-VO, 10-minute occlusion, 7-day survival) or distal middle cerebral artery occlusion (MCAo, 90-minute occlusion, 22.5-hour survival). In global ischemia, treatments were given immediately after ischemia (experiment 1) or as preischemic and postischemic treatments (experiment 2). Three focal ischemia experiments were done. Injection times were 60 minutes into ischemia (experiment 1) and 60 minutes into ischemia plus 30 and 120 minutes after ischemia (experiment 2). Experiment 3 was identical to experiment 2 except that a 30-minute preischemia treatment was instituted. Core normothermia was maintained in all experiments during ischemia. However, in the last focal and global experiments, core and brain temperatures, respectively, were also measured after ischemia with telemetry probes. Because hyperthermia accompanied z-DEVD treatment, an extra z-DEVD-treated group (MCAo) was included with temperature clamped at normothermia. RESULTS: Neither z-VAD nor z-DEVD significantly reduced CA1 injury after global ischemia. In focal ischemia, both drugs significantly reduced infarction, but only in the third experiment, and the prevention of hyperthermia that accompanied z-DEVD treatment did not alter this. CONCLUSIONS: These results suggest a detrimental role of caspases in moderately severe focal but not global cerebral ischemia.     

Role of prosaposin in the male reproductive system: effect of prosaposin inactivation on the testis, epididymis, prostate, and seminal vesicles

SGP-1/prosaposin can be secreted or targeted to the lysosomes where it is processed into smaller saposins (A, B, C, and D) required for the hydrolysis of glycosphingolipids. The deficiency of saposins B and C results in variant forms of metachromatic leukodystrophy and Gaucher's disease, respectively, which are characterized by lysosomal storage of undegraded glycosphingolipids. In the nervous system, prosaposin presents trophic activity. A mouse model was recently developed by creating a null allele in embryonic stem cells through gene targeting to investigate the phenotypic diversity of prosaposin mutations and the involvement of this protein in lysosomal storage diseases, and for the development of therapeutic approaches. Mice homozygous mutants die at the age of 35-40 days and neurological disorders contribute to the early demise of the mutant mice. The male reproductive organs in homozygous mutants show several abnormalities, such as a decrease in testis size with reduced spermiogenesis and an involution of the prostate, seminal vesicles, and epididymis. In these animals, the blood levels of testosterone remain normal. In the prostate of homozygous mutants, only the basal epithelial cells appear to be present, while the secretory cells are absent. These findings suggest that prosaposin may be involved in the development and maintenance of the male reproductive organs, as well as, in cellular differentiation.     

Targeted disruption of the mouse prosaposin gene affects the development of the prostate gland and other male reproductive organs

The prosaposin gene encodes a 65-70 kilodalton (kd) protein, which is secreted or targeted to lysosomes. In lysosomes, prosaposin is the precursor of 4 activator proteins, designated saposins A, B, C, and D, which promote by acidic hydrolases, the degradation of glycosphingolipids with short oligosaccharide chains. Mutations of the prosaposin gene have been linked to several lysosomal storage disorders. An animal model was recently developed by creating a null allele in embryonic stem cells through gene targeting in order to investigate the phenotypic diversity of prosaposin mutations, the involvement of this protein in lysosomal storage diseases, and to develop potential therapeutic approaches. Mutant homozygous mice die at 35-40 days of age and neurological disorders contribute to their early death. Secreted prosaposin is present in milk and in cerebrospinal and seminal fluids. In the nervous system, prosaposin exhibits a trophic activity. Examination of reproduc-tive organs in homozygous mutant males shows several abnormalities such as a decrease in testis size with reduced spermiogenesis, and an involution of the prostate, seminal vesicle, and epididymis, although levels of testosterone in blood remain normal. In the prostate of homozygous mutants, only basal cells appear to be present, whereas secretory cells are absent. The epithelia in efferent ducts is formed by ciliated cells, whereas heterozygotes exhibit a majority of nonciliated cells. Our data indicate that prosaposin is involved in the development and maintenance of male reproductive organs. In prostatic epithelium, targeted disruption of the prosaposin gene appears to inactivate the mitogen-activated protein kinase pathway and to interfere with differentiation of secretory cells.     

双侧带蒂肾上腺背部皮下移位术治疗柯兴病

目的 进一步探讨柯兴病的手术方法。方法 采用双侧带蒂肾上腺背部皮下移位术治疗柯兴病患者１６例。结果 术后随访１４例患者４～４８个月,疗效满意,无复发,仅３例皮质功能稍低下者,以小剂量皮质激素即可维持。余１１例患者临床症状消失,血皮质醇及２４小时尿１７羟皮质类固醇、１７酮类固醇降至正常范围。结论 双侧带蒂肾上背部皮下移位术是治疗柯兴病合理的、较满意的方法。     

VEGF、KDR的表达对肝癌的血管生成、生长、转移的影响

目的　研究血管内皮生长因子 (VEGF)及其受体KDR(kinaseinsertdomaincontainingre ceptor)对肝细胞肝癌的血管生成、生长、转移等方面的影响。　方法　对 45例肝癌、2 1例肝硬化、8例正常肝标本进行了免疫组化、原位杂交染色 ,然后行图像分析 ,观察VEGF、KDR的表达与肝癌病理特点之间的关系 ,并进行统计学分析。　结果　肝细胞肝癌中VEGF高表达 ;并与肝癌的血管生成相关 ;VEGF的表达强度与表达率均与肝癌的转移、包膜形成相关 ;KDR不仅表达于血管内皮细胞 ,还表达于部分肝癌细胞。　结论　VEGF在肝癌的血管生成、癌细胞转移、包膜形成中可能起到重要作用 ,KDR在肝癌细胞的表达可能是一种自分泌行为。