Bone marrow transplantation in dogs after radio-ablation with a new Ho- 166 amino phosphonic acid bone-seeking agent (DOTMP)

beta-emitting 166Ho (t1/2 = 26.78 hours, E(beta)max = 1.8 MeV) complexed with the phosphonic acid chelator, 1,4,7,10 tetraazacyclododecane-1,4,7,10-tetra(methylene phosphonic acid) (DOTMP) at a ligand-to-metal ratio of 1.5:1 binds to bone. This radioactive complex is a marrow-ablating radiopharmaceutical that appears useful for preparation of bone marrow (BM) transplant recipients without the morbidity usually associated with total body irradiation preparatory regimens. We have found with seven splenectomized young adult beagle dogs that a 166Ho radiopharmaceutical dosage of 370 MBq/kg body weight provides an initial skeletal radioactivity burden of at least 1.5 GBq/kg skeleton and results in complete ablation of hematopoietic marrow cell populations within 7 days. The beta particle flux distribution in BM-forming skeletal tissue is not uniform. Red marrow radiation doses varied from 30 to 115 Gy as estimated by direct radioassay and autoradiographic analyses of both bone biopsies and postmortem samples; the median value of 61 Gy agreed with our theoretical expectations. In vivo radioactivity distribution was evaluated with nuclear imaging methods. Apparently, normal hematopoiesis was restored in three dogs with autologous BM transplants performed 5 to 6 days after administration of the marrow ablative radiopharmaceutical, 166Ho-DOTMP. BM biopsies at 7 to 10 months posttransplantation indicate continued normal hematopoietic activity.     

Decreased nucleotide and serotonin storage associated with defective function in Chediak-Higashi syndrome cattle and human platelets

Prolonged mean template bleeding time of 14 min observed in seven cattle with the Chediak-Higashi syndrome (CHS) prompted the examination of platelet function in these animals. There was no distinguishable difference in concentration of circulating platelets between CHS and control cattle. CHS bovine platelets failed to aggregate in vitro in response to concentrations of acid-soluble collagen which induced aggregation in all normal samples. The primary platelet response to 5 muM ADP was normal in CHS cattle. A markedly decreased amount of serotonin (1.2% of normal) was detected in CHS bovine platelets. Bovine CHS platelet ATP and ADP contents were significantly less than normal, and the ATP/ADP ratios were 5.04 in normal and 29.38 in CHS platelets. Results of these animal investigations prompted a similar study of two patients with CHS. In humans, an increased bleeding time greater than 15 min and an in vitro impaired aggregation response to acid-soluble collagen and 5 muM adrenaline were discovered. Both ATP and ADP were reduced in CHS human platelets, and the ATP/ADP ratio was 3.96, compared to a ratio of 1.52 for platelets of two normal subjects. These findings suggested the presence of a "storage pool disease" of CHS platelets.     

Distinct mutation patterns of breast cancer-associated alleles of the HRAS1 minisatellite locus

DNA sequence analysis of 130 alleles of the HRAS1 minisatellite has demonstrated that breast cancer-associated variants arise as a consequence of both replication errors and gene conversions. Unlike mutations at other variable number of tandem repeats (VNTRs), high-risk variants of the HRAS1 minisatellite do not demonstrate positional polarity. Instead, most mutations occur at three hotspots, with replication errors confined to one hotspot, gene conversions to a second and a mixed pattern of mutation at the third. DNA sequence analysis of 66 low-risk a1 alleles revealed no evidence for hypermutation. Therefore, while the HRAS1 minisatellite may serve as a reporter for a broad-based group of mutational mechanisms, these results are consistent with a direct pathogenetic contribution by high- risk alleles as the biological basis underlying cancer association of this VNTR.      

《亚洲男性学杂志》“21世纪精液分析特刊”前言

精液分析成为不育研究的重要部分经历了一个极其漫长的历史变迁过程，并声名狼藉，曾经被排除在常规的病理学检查之外，直到近些年才引起学术界的重视。精液分析起源于19世纪，那时对精子的认识仅仅局限于检测性交后宫颈黏液中是否存在精子，曾认为是“有失体面的，不自重的^[1]。”     

提高人类精液中圆形细胞数量测定的精确度

本研究的目的是提高用过氧化物酶试验检测精液中的白细胞时所得的圆形细胞数量的精确度。精液样本的圆形细胞浓度在(0.6~6)×106/mL之间,降低精液的稀释度,增加被测悬浮液的体积。1+5(1∶6)的稀释度适合于测量过氧化物酶活性,并能为细胞检测提供足够清晰的背景。在该稀释度下,测定Neubauer-改良精子计数板两边所有18个网格中的细胞数量,额定细胞浓度为(1.9~3.3)×106/mL的10个样本中只有3个样本的圆形细胞数≥400个。由于更低浓度的精子稀释液不适合测定圆形细胞或其过氧化物酶反应产物,所以无法精确测量(抽样误差5%)参考下限值(1×106/mL)。结果表明,正是由于测定精液中的10个样本中圆形细胞很难精确到1×106/mL,所以白细胞精液症临界值的确定一直存在诸多分歧。因此需要建立一些统计学上合理的参考限。