Unusual features in children with inv dup(15) supernumerary marker: a study of genotype-phenotype correlation in Taiwan

Recent molecular cytogenetic studies have elucidated the origin and nature of extra structurally abnormal chromosomes (ESACs) or small supernumerary chromosomes, which are often associated with developmental delay and malformations. We studied the prevalence of inv dup(15) in a nationwide screening programme for mentally retarded children in Taiwan and tried to correlate the genotype and phenotype in those patients. Fluorescence in situ hybridization (FISH) analysis using D15Z, D15Z1, and the cosmids from the Prader-Willi/Angelman syndrome chromosome region (PW/ASCR) was performed on 54 patients (0.45%) with ESACs from 11893 probands within a 5-year period. Of them, inv dup(15) was confirmed in 25 children (46.3%) by FISH analysis. The PW/ASCR probes were used to clarify the size and DNA composition of the markers. Patients with inv dup(15) chromosomes, containing only the heterochromatin or little euchromatin of the proximal 15q (i.e., pter→q11:q11→pter) may have a rather mild or nearly normal phenotype (group 1). Only one patient had some features suggestive of Angelman syndrome, but was considered to be a result of deleted (15)(q12) in the chromosome 15 homologue. Additional copies within D15S11 through GABRB3 (15q11.2-13) resulted in an abnormal phenotype which involved mental and developmental delay but was different from the classical phenotype of PW/AS (groups 2, 3). Signs of autistic behavior did occur in each group. FISH combined with microsatellite analyses showed that the marker was often of maternal origin in de novo cases (n = 12, 86%), or inherited from the mother in only one familial case. Down-inv dup(15) was mentioned in two cases. Unusual features including diaphragmatic eventration, hyperlaxity of joints, arachnodactyly, brain atrophy, epilepsy (particularly infantile spasm), ataxia, genital abnormalities, and cleft lip/palate were noted in those patients. This observation expands the range of phenotypic expression associated with this relatively common ESAC. Conclusion Marked phenotypic diversities exist in children with inv dup(15), dependent upon the size or genetic composition of the markers, degree of mosaicism, parental origin and familial occurrence or not. Patients with a larger inv dup(15) marker chromosome including the PW/ASCR may have a higher risk of abnormalities, but not the typical Prade-Willi/Angelman syndrome phenotype. Received: 11 February 1997 and in revised form: 20 May 1997 / Accepted: 20 May 1997     

Spectrum of point mutations in the coding region of the hypoxanthine- guanine phosphoribosyltransferase (hprt) gene in human T-lymphocytes in vivo

The hypoxanthine-guanine phosphoribosyl transferase (hprt) locus in 6- thioguanine (TG) resistant T-lymphocytes is a useful target for the study of somatic in vivo mutagenesis, since it provides information about a broad spectrum of mutation. Mutations in the hprt coding region were studied in 124 TG-resistant T-cell clones from 38 healthy, non- smoking male donors from a previously studied population of bus maintenance workers, fine-mechanics and laboratory personnel. Their mean age was 43 years (range 23-64) and their hprt mutant frequency was 9.3 +/- 5.2 x 10(-6) (mean +/- SD, range 1.4-22.6 x 10(-6)). Sequence analysis of hprt cDNA identified 115 unique mutations; 76% were simple base substitutions, 10% were +/-1 bp frameshifts, and 10% were small deletions within exons (3-52 bp). In addition, two tandem base substitutions and one complex mutation were observed. Simple base substitutions were observed at 55 (20%) of 281 sites known to be mutable in the hprt coding sequence. The distribution of these mutations was significantly different than would be expected based upon a Poisson distribution (P < 0.0001), suggesting the existence of 'hotspots'. All of the 87 simple base substitutions occurred at known mutable sites, but eight were substitutions of a kind that have not previously been reported at these sites. The most frequently mutated sites were cDNA positions 197 and 146, with six and five independent mutations respectively. Four mutations were observed at position 131, and three each at positions 143, 208, 508 and 617. Transitions (52%) were slightly more frequent than tranversions (48%), and mutations at GC base pairs (56%) more common than mutations at AT base pairs (44%). GC > AT was the most common type of base pair substitution (37%). The majority of the mutations at GC base pairs (78%) occurred at sites with G in the non-transcribed strand. All but one of eight mutations at CpG- sites were of the kind expected from deamination of methylated cytosine. Deletion of a single base pair (-1 frameshift) was three times more frequent than insertion of a single bp (+1 frameshift). Almost half (6/13) of the small (3-52 bp) deletions within the coding sequence clustered in the 5' end of exon 2. Short repeats and other sequence motifs that have been associated with replication error were found in the flanking regions of most of the frameshifts and small deletions. However, several differences in the local sequence context between +/-1 frameshift and deletion mutations were also noticed. The present results identify positions 197, 146 and possibly 131 as hotspots for base substitution mutations, and confirm previously reported hotspots at positions 197, 508 and 617. In addition, the earlier notion of a deletion hotspot in the 5'end of exon 2 was confirmed. The observations of these mutational cluster regions in different human populations suggest that they are due to endogeneous mechanisms of mutagenesis, or to ubiquitous environmental influences. The emerging background spectrum of somatic in vivo mutation in the human hprt gene provides a useful basis for comparisons with radiation or chemically induced mutational spectra, as well as with gene mutations in human tumors.      

急性脑梗塞患者血管内皮细胞活性因子的变化和活血化瘀对其影响的临床观察

为探讨急性脑梗塞中医不同证型与血管内皮细胞的关系，以及活血化阏对其影响。方法对２０名健康得及６６例ＡＣＩ偏虚证和偏实证患者检测了血浆纤缩溶解系统，前列环素系统以及第Ⅷ因子相关抗原等的水平。     

A preliminary study on alternation of generations of Cordyceps sinensis (Berkey) Sacc.]

The insect pathogeny of parasitic hepialus by Cordyceps sinensis is, reported in this paper. The infestation of hepialus larvae by Cordyceps sinensis, growth and reproduction of hypha body in the hemolymph of host larvae, growth of stroma, maturity of hymenium and the abjection and germination of ascospores were observed.     

The effect of Rhodiola capsules on oxygen consumption of myocardium and coronary artery blood flow in dogs]

It has been proved that Rhodiola Capsules can obviously decrease the oxygen consumption of myocardium and oxygen consumption index in anesthetic dogs, decrease the coronary artery resistance, but have no marked effect on the coronary artery blood flow. The Capsules also have the function of decreasing blood presure and slowing heart rate.     

Compatible leaching effect of Concha Ostreae and some commonly-used Chinese medicinal materials]

OBJECTIVE: Based on a study of Concha Ostreae, to provide some reference for the rational approach to leaching mineral drugs. METHOD: Taking the change rates of compatible leaching and value of A as targets, the compatible leaching effect of Concha Ostreae with Radix et Rhizoma Rhei Praeparata, Radix Scutellariae, Pollen Typhae and Fructus Aurantii lmmaturus was studied. RESULT: If Concha Ostreae and the above cited medicinal herbs are decocted together, the yield of extract may be reduced to a certain extent, but the target composition of Radix et Rhizoma Rhei Praeparata and Fructus Aurantii lmmaturus remains intact, only the content of Radix Scutellariae baicalin may be influenced. CONCLUSION: The relationship of technology with preparation must be taken into consideration when making choice of the proper way to leach Concha Ostreae.     

健脾补肾法治疗重症肌无力3O2例

目的：探讨健脾补肾法治疗重症肌无力的疗效。方法：选符合纳入标准的重症肌无力患者426例，随机分为两组。治疗组予健脾补肾中药，对照组予肾上腺皮质激素或免疫抑制剂。两组均治疗6个月观察疗效。结果：治疗组痊愈59例，显效93例，有效116例，无效34例，总有效率为88．7％(95％CI=85．1％～92．3％)；对照组痊愈21例，显效29例，有效40例，无效34例，总有效率为72.6％(95％CI=64．7％～80．5％)；两组综合疗效比较，有明显差异(u=2．6438，P=0．0091)。结论：健脾补肾法治疗重症肌无力疗效优于甲基强的松龙或环磷酰胺，其收益为OR=0．34(95％CI=0．20～0．57)，NNT=6(95％CI=4．20～11．76）。     

银杏叶提取物EGb761通过caspase-3抑制TNF-α诱导HeLa细胞凋亡

目的探讨caspase-3的活化在银杏叶提取物EGb761对肿瘤坏死因子-α(TNF-α)诱导HeLa细胞凋亡中的影响.方法采用流式细胞术检测细胞凋亡,Western blot检测caspase-3 p20活性片段,Caspase-3 Colorimetric Assay试剂盒测定caspase-3活性.结果流式细胞术分析结果显示,EGb761在10～40 mg/L终浓度范围内对重组人肿瘤坏死因子-α(rhTNF-α)诱导的HeLa细胞凋亡均有显著的抑制作用(P＜0.01),呈剂量依赖关系;Western blot检测显示,rhTNF-α诱导的HeLa细胞caspase-3 p20活性片段水平增高,能被不同剂量EGb761(10～40 mg/L)明显抑制,且随EGb761浓度增加抑制效果增强;caspase-3活性测定结果显示,EGb761对rhTNF-α诱导的caspase-3活化有显著的抑制作用,且随剂量增加抑制作用增强.结论结果提示,EGb761抑制TNF-α诱导的HeLa细胞凋亡可能与其抑制caspase-3活化有关.