A comparison of the bronchodilator activity of Sch 1000 and salbutamol.

The effects of the beta 2-adrenergic agonist, salbutamol, 200 mug, and the cholinergic antagonist, Sch 1000, 40 mug, have been compared in 25 asthmatic patients using a single dose, double-blind, crossover trial design. Salbutamol aerosol produces a greater degree of bronchodilatation than Sch 1000 aerosol during the initial three hours following drug administration. There is no significant difference in the bronchodilator effects of the two drugs in the interval four to eight hours after drug administration. Nonatopic patients showed less difference in bronchodilator response to each of the two drugs than atopic patients. Neither drug showed any significant adverse effect on blood pressure, pulse rate, or electrocardiogram. In six asthmatic patients the effect of the combination of salbutamol, 200 mug, and Sch 1000, 40 mug, was evaluated. The combination produced a longer duration of bronchodilatation than either drug alone when compared to placebo.     

鄂伦春族Y染色体短串联重复序列多态性研究

目的 调查鄂伦春族Y染色体上10个短串联重复序列基因座及单倍型的遗传多态性。方法 应用PCR和变性聚丙烯酰胺凝胶电泳结合银染显色分型技术，检测102名无关系鄂伦春族男性血样。结果 在DYS392、DYS438、DYS439、DYS456、DYS459、DYS460、DYS461、DYS462、DYS389Ⅰ、DYS389Ⅱ等10个基因座中共检出44个等位基因，等位基因频率分布在0．418（DYS461）至0．727（DYS389Ⅰ）之间，除了DYS461（0．418）和DYS462（0．479）以外，其余等位基因频率均大于0．5。由10个基因座组成的Y染色体单倍型系统单倍型有101种，单倍型频率0．99。结论 上述10个Y-短串联重复基因座在鄂伦春族群体中具有较好的多态性，单倍型具有很高的遗传多态性。     

Spermatozoal nuclear determinants of reproductive outcome: implications for ART

A male factor is implicated in more than 50% of couples treated with IVF. However, neither the routine testing of male fertility potential nor its treatment address the specific mechanisms by which spermatozoal factors may impact upon reproductive outcome. An important function of spermatozoa is to deliver the paternal genome to the oocyte. Recently, a number of acquired spermatozoal nuclear factors that may have implications on reproductive outcome have been described. These include non-specific DNA strand breaks, numerical abnormalities in spermatozoal chromosome content, Y chromosome microdeletions and alterations in the epigenetic regulation of paternal genome. The exact mechanisms by which these factors affect reproduction are unknown and their implications for assisted reproduction technology outcome need to be further investigated. These recent findings point to the need for novel and more personalized approaches to test and treat male factor infertility.     

The prognostic role of the extent of Y microdeletion on spermatogenesis and maturity of Sertoli cells

Substantial involvement of the Y chromosome in sexual development and spermatogenesis has been demonstrated. Over the last decade, varying extent of Y chromosome microdeletions have been identified among infertile patients with azoospermia or oligozoospermia. These microdeletions were clustered in three main regions named AZFa, AZFb, and AZFc. Analysis of the Y chromosome microdeletion was found to be of prognostic value in cases of infertility, both in terms of clinical management as well as for understanding the aetiology of the spermatogenesis impairment. However, the accumulated data are difficult to analyse, due to the variable extent of these deletions, the different sequence-tagged sites (STS) used to detect the microdeletions, and the non-uniformity of the histological terminology used by different investigators. This debate discusses the chances of finding testicular spermatozoa in men with a varying extent of Y chromosome microdeletions. The genotype and germ cell findings in men with AZFa microdeletions as well as those that include more than a single AZF region are reviewed, as is the effect of Y chromosome AZF microdeletions on the maturity of the Sertoli cells.     

Construction of a highly enriched marsupial Y chromosome-specific BAC sub-library using isolated Y chromosomes

The Y chromosome is perhaps the most interesting element of the mammalian genome but comparative analysis of the Y chromosome has been impeded by the difficulty of assembling a shotgun sequence of the Y. BAC-based sequencing has been successful for the human and chimpanzee Y but is difficult to do efficiently for an atypical mammalian model species (Skaletsky et al. 2003, Kuroki et al. 2006). We show how Y-specific sub-libraries can be efficiently constructed using DNA amplified from microdissected or flow-sorted Y chromosomes. A Bacterial Artificial Chromosome (BAC) library was constructed from the model marsupial, the tammar wallaby (Macropus eugenii). We screened this library for Y chromosome-derived BAC clones using DNA from both a microdissected Y chromosome and a flow-sorted Y chromosome in order to create a Y chromosome-specific sub-library. We expected that the tammar wallaby Y chromosome should detect ∼100 clones from the 2.2 times redundant library. The microdissected Y DNA detected 85 clones, 82% of which mapped to the Y chromosome and the flow-sorted Y DNA detected 71 clones, 48% of which mapped to the Y chromosome. Overall, this represented a ∼330-fold enrichment for Y chromosome clones. This presents an ideal method for the creation of highly enriched chromosome-specific sub-libraries suitable for BAC-based sequencing of the Y chromosome of any mammalian species.     

Natural transmission of a partial AZFb deletion of the Y chromosome over three generations: case report

The natural transmission of microdeletions of the Y chromosome is occasionally reported in the literature. Here we describe the natural transmission of a partial AZFb deletion over three generations. PCR amplification of several sequence tagged site markers in the three AZF regions of the Y chromosome was carried out in a patient with oligoasthenoteratozoospermia, his father and his naturally conceived son. The deletion was confirmed by Southern blotting. The propositum, his father and his son showed a probably identical, partial deletion of the distal part of the AZFb region, involving sY130 and sY143. The deletion was confirmed by Southern blotting using the sY130 probe. Partial AZFb microdeletions can be associated with moderate oligozoospermia allowing natural conception and therefore natural transmission of this genetic anomaly. Further studies are needed to define the pathogenetic significance of microdeletions involving sY130 and sY143.     

男性不育患者Y染色体微缺失的研究

目的研究无精子症和少精子症患者与Y染色体位点缺失的相关性，建立Y染色体微缺失的分子诊断方法。方法采用多重PCR技术对53例染色体核型正常的无精子症和少精子症患者以及5例正常男性的无精子因子（azoospermia factor，AZF）区域的6个STS位点进行检测。结果5例精液正常男性未检出Y染色体微缺失；53例患者中6例有AZF区域的微缺失，总缺失率为11．3％。结论Y染色体微缺失是严重生精障碍的重要原因之一，无精子因子（AZF）候选基因在精子发生过程中可能起重要作用。     

Co-localization of neuropeptide Y, vasoactive intestinal polypeptide and dynorphin in non-noradrenergic axons of the guinea pig uterine artery

Two major populations of perivascular axons containing immunoreactivity to neuropeptide Y (NPY) have been revealed in the main uterine artery of the guinea pig by immunohistochemical procedures which allow the simultaneous visualization of two antigens. One population contained immunoreactivity to dopamine-beta-hydroxylase (D beta H) and was presumably noradrenergic. The other main population of axons with NPY-like immunoreactivity (NPY-LI) did not have D beta H-like immunoreactivity (D beta H-LI) and was presumably non-noradrenergic. These non-noradrenergic axons also contained immunoreactivity to vasoactive intestinal polypeptide (VIP) and dynorphin (DYN). Indeed, nearly all axons with VIP-LI also contained NPY-LI and DYN-like immunoreactivity (DYN-LI). NPY constricted the uterine artery perfused in vitro, whilst VIP dilated uterine arteries preconstricted with noradrenaline or NPY. Thus, we have evidence for the coexistence of a vasoconstrictor peptide and a vasodilator peptide in the same non-noradrenergic perivascular axons, which also contain an opioid peptide, dynorphin.     

Mitochondrial DNA and Y-Chromosome Variation in the Caucasus

We have analyzed mtDNA HVI sequences and Y chromosome haplogroups based on 11 binary markers in 371 individuals, from 11 populations in the Caucasus and the neighbouring countries of Turkey and Iran. Y chromosome haplogroup diversity in the Caucasus was almost as high as in Central Asia and the Near East, and significantly higher than in Europe. More than 27% of the variance in Y‐haplogroups can be attributed to differences between populations, whereas mtDNA showed much lower heterogeneity between populations (less then 5%), suggesting a strong influence of patrilocal social structure. Several groups from the highland region of the Caucasus exhibited low diversity and high differentiation for either or both genetic systems, reflecting enhanced genetic drift in these small, isolated populations. Overall, the Caucasus groups showed greater similarity with West Asian than with European groups for both genetic systems, although this similarity was much more pronounced for the Y chromosome than for mtDNA, suggesting that male‐mediated migrations from West Asia have influenced the genetic structure of Caucasus populations.     

A new haplogroup pattern displayed in Fujian Han in China

Human Y-chromosomal binary polymorphisms have been considered to preserve the paternal genetic legacy and provide evidence on human evolution and the genetic relationships among and demographic history of different populations. To reveal the genetic origin and immigration of the Fujian Han, 13 binary markers on the Y chromosome were used to screen Fujian Han by allele-specific polymerase chain reaction. The results indicated that the M₉G marker was highly prevalent (96.20%), suggesting a significant genetic drift. In addition, M₁₂₂C frequency was only 22.78%, and M₄₅A and M₁₀₃T were default. The distinctive haplogroup frequencies (H₁, H₅, and H_6/7/8) imply that the haplogroup pattern is a relatively ancestral and interim type. Received: October 13, 2001 / Accepted: December 3, 2001