Immunohistochemical localization of membrane and alpha-granule proteins in plastic-embedded mouse bone marrow megakaryocytes and murine megakaryocyte colonies

Using an immunoperoxidase technique that permits optimal antigen localization at the light microscope level, we have detected two platelet alpha-granule constituents and three platelet membrane glycoproteins in mouse bone marrow megakaryocytes and in murine megakaryocyte colonies grown in soft agar culture for three to seven days. Using polyclonal antibodies prepared against human platelet proteins, we have demonstrated labeling for von Willebrand factor, fibrinogen, and the membrane glycoproteins IIIa and GMP-140 in both bone marrow megakaryocytes and megakaryocyte colonies after seven days of culture. Using monoclonal antibodies to membrane glycoproteins IIb and GMP-140, we have demonstrated label in mouse bone marrow megakaryocytes. Granulocyte and macrophage colonies were negative for each of these markers. Murine bone marrow megakaryocytes and megakaryocyte colonies demonstrated a similar enzyme histochemical pattern: weakly positive for alpha-naphthyl acetate esterase and negative for chloroacetate esterase. These data indicate that megakaryocytes grown in soft agar culture express many of the same glycoproteins as bone marrow megakaryocytes. Furthermore, the ability of antibodies directed against human platelet membrane glycoproteins to identify murine megakaryocyte glycoproteins indicates that these constituents have been highly conserved during evolution.     

Quantifying the risks and benefits of efavirenz use in HIV‐infected women of childbearing age in the USA

Objectives

The aim of the study was to quantify the benefits (life expectancy gains) and risks (efavirenz‐related teratogenicity) associated with using efavirenz in HIV‐infected women of childbearing age in the USA.

Methods

We used data from the Women's Interagency HIV Study in an HIV disease simulation model to estimate life expectancy in women who receive an efavirenz‐based initial antiretroviral regimen compared with those who delay efavirenz use and receive a boosted protease inhibitor‐based initial regimen. To estimate excess risk of teratogenic events with and without efavirenz exposure per 100 000 women, we incorporated literature‐based rates of pregnancy, live births, and teratogenic events into a decision analytic model. We assumed a teratogenicity risk of 2.90 events/100 live births in women exposed to efavirenz during pregnancy and 2.68/100 live births in unexposed women.

Results

Survival for HIV‐infected women who received an efavirenz‐based initial antiretroviral therapy (ART) regimen was 0.89 years greater than for women receiving non‐efavirenz‐based initial therapy (28.91 vs. 28.02 years). The rate of teratogenic events was 77.26/100 000 exposed women, compared with 72.46/100 000 unexposed women. Survival estimates were sensitive to variations in treatment efficacy and AIDS‐related mortality. Estimates of excess teratogenic events were most sensitive to pregnancy rates and number of teratogenic events/100 live births in efavirenz‐exposed women.

Conclusions

Use of non‐efavirenz‐based initial ART in HIV‐infected women of childbearing age may reduce life expectancy gains from antiretroviral treatment, but may also prevent teratogenic events. Decision‐making regarding efavirenz use presents a trade‐off between these two risks; this study can inform discussions between patients and health care providers.     

精子释放时精子质量的检测方法

评价新修订的《世界卫生组织人类精液分析实验室技术手册》(简称手册)中涉及精子释放(精子脱离支持细胞从睾丸中排出)时的精子特征。修订手册的目的是在不影响临床应用的情况下改善"精液分析的质量"。手册指出,精液分析还有助于①研究男性生殖状态。②在男性生殖调节期间和之后监测精子的发生状态。但是,如果对射精精液精子的分析是用于上述②的目的,那么就必须识别出精子释放时的异常精子。手册未提出精子释放时精子质量的检测方法。相反,采用了精子穿过宫颈黏液或到达受精位置这一"金标准"。这个标准虽然适合于判断个体使其伴侣妊娠的可能性,但却不适用于研究睾丸本身的疾病。因此,手册介绍的测定精子质量的方法无法鉴别精子异常是发生在精子释放同时还是之后。基于活动或"活"精子的百分率评价精子释放时的精子质量是没有意义的。介绍了能反映精子释放时精子质量的其他特征,基于射出精液中单个精子的质量特征评价精子释放时精子质量可采用以下方法:①采用新的精子质量形态评估体系。②采用现代技术评价一定样本中单个精子的几个合适和独立的特征,以便更准确地确定异常精子的比例。