BACKGROUND & AIMS: :Osteopontin (OPN) is a secreted extracellular matrix phosphoprotein identified in various tissues and fluids including those of the male and female reproductive tracts. OPN was previously identified as a 55 kDa high fertility marker in Holstein bull seminal plasma, produced by the ampulla and the vesicular gland. The objectives of this study were to characterize OPN on ejaculated and cauda epididymal sperm using immunofluorescence and western blot analysis, and to assess the role of sperm OPN in fertilization. Solubilized sperm membrane proteins from ejaculated and cauda epididymal sperm were separated by 1D SDS-PAGE, transferred to nitrocellulose, and probed with an antibody to bovine milk OPN. A 35 kDa protein was detected by this antibody in both ejaculated and cauda epididymal sperm membranes. Analyses also recognized OPN at 55 and 25 kDa in cauda epididymal fluid and testicular parenchyma homogenates respectively. Immunofluorescent analysis of ejaculated and cauda epididymal sperm showed OPN localization in a well-defined band in the postacrosomal region of the sperm head and also on the midpiece. Results of in vitro fertilization experiments showed that sperm treated with an antibody to OPN fertilized fewer oocytes than sperm treated with control medium while increasing incidence of polyspermy, suggesting a role of sperm-associated OPN in fertilization and a block to polyspermy. These studies demonstrate that OPN exists at multiple molecular weight forms in the bull reproductive tract and its presence on ejaculated sperm may signal its importance in fertilization by interacting with integrins or other proteins on the oocyte plasma membrane.

背景与目标： : 骨桥蛋白 (OPN) 是一种分泌的细胞外基质磷蛋白，在包括男性和女性生殖道在内的各种组织和体液中鉴定出。OPN先前被确定为由壶腹和水泡腺产生的荷斯坦公牛精浆中的55 kDa高生育力标记。这项研究的目的是使用免疫荧光和western blot分析来表征射精和附睾尾精子的OPN，并评估精子OPN在受精中的作用。通过1D sdds-PAGE分离来自射精和附睾尾精子的溶解的精子膜蛋白，转移至硝酸纤维素，并用牛乳OPN抗体探测。该抗体在射精和附睾尾精子膜中均检测到35 kDa蛋白。分析还分别在尾附睾液和睾丸实质匀浆中识别出55 kDa和25 kDa的OPN。对射精和附睾尾精子的免疫荧光分析显示，OPN定位在精子头部顶体后区域和中段的明确定义的条带中。体外受精实验的结果表明，用OPN抗体处理的精子比用对照培养基处理的精子受精的卵母细胞少，同时增加了多精子的发生率，这表明与精子相关的OPN在受精中的作用以及对多精子的阻断。这些研究表明，OPN以多种分子量形式存在于公牛生殖道中，并且其在射精精子上的存在可能通过与卵母细胞质膜上的整联蛋白或其他蛋白质相互作用来表明其在受精中的重要性。

BACKGROUND & AIMS: :Primary B-cell lymphoma of the testis, breast and thyroid are rare and data concerning cytogenetic aberrations at these extranodal sites are scarce. We examined the presence of extranodal marginal zone lymphoma-associated translocations, t(11;18)(q21;q21), t(1;14)(p22;q32), t(14;18)(q32;q21), t(3;14)(p14.1;q32) and numerical aberrations of chromosomes 1, 3, 12 and 18 by fluorescence in situ hybridization in 6 extranodal marginal zone lymphomas and 24 diffuse large B-cell lymphomas with (n=9) or without (n=15) marginal zone lymphoma components, with primary localizations in the breast (n=15), testis (n=9) and thyroid (n=6). We found t(14;18)(q32;q21), with breakpoints in IGH and MALT1, in one testicular diffuse large B-cell lymphoma and in two diffuse large B-cell lymphomas of the breast. No other translocations, amplifications or deletions involving IGH, BCL-10, BCL-2, MALT1 and IAP2 were detected. Numerical aberrations occurred in 67% of the lymphomas, 67% of extranodal marginal zone lymphomas, 56% of diffuse large B-cell lymphomas with marginal zone lymphoma components and in 73% of 'de novo' diffuse large B-cell lymphomas. These included 78% of testis, 67% of thyroid and 60% of breast lymphomas, and included mainly trisomy 18 (n=16), trisomy 3 (n=8) and trisomy 1 (n=3). One testicular diffuse large B-cell lymphoma harbored both t(14;18)(q32;q21) and trisomy 3. Our results indicate that at least a few cases of diffuse large B-cell lymphoma of the testis and the breast belong to the spectrum of extranodal marginal zone lymphoma.

背景与目标： : 睾丸，乳腺和甲状腺的原发性b细胞淋巴瘤很少见，有关这些结外部位的细胞遗传学畸变的数据很少。我们检查了结外边缘区淋巴瘤相关易位的存在，t(11;18)(q21;q21)，t(1;14)(p22;q32)，t(14;18)(q32;q21)，t(3;14)(p14.1;q32) 和通过荧光原位杂交在6个结外边缘区淋巴瘤和24个弥漫性大b细胞淋巴瘤中有 (n = 9) 或没有 (n = 15) 边缘区淋巴瘤成分的染色体1、3、12和18的数字畸变，原发性定位在乳房 (n = 15)，睾丸 (n = 9) 和甲状腺 (n = 6)。我们在一个睾丸弥漫性大b细胞淋巴瘤和两个弥漫性大b细胞淋巴瘤中发现t(14;18)(q32;q21)，在IGH和MALT1中具有断点。未检测到涉及IGH，BCL-10，BCL-2，MALT1和IAP2的其他易位，扩增或缺失。数值畸变发生在67% 淋巴瘤，67% 结外边缘区淋巴瘤，56% 具有边缘区淋巴瘤成分的弥漫性大b细胞淋巴瘤以及73% “从头” 弥漫性大b细胞淋巴瘤中。这些包括睾丸78%，甲状腺67% 和乳腺淋巴瘤60%，主要包括18三体综合征 (n = 16)，3三体综合征 (n = 8) 和1三体综合征 (n = 3)。一种睾丸弥漫性大b细胞淋巴瘤同时患有t(14;18)(q32;q21) 和三体综合征3。我们的结果表明，至少有几例睾丸和乳房的弥漫性大b细胞淋巴瘤属于结外边缘区淋巴瘤的范围。

BACKGROUND & AIMS: Inhibin/activin subunit (alpha, beta A, and beta B) immunoreactive protein localization patterns and cell type specific inhibin alpha-subunit mRNA expression have been examined in early- to midgestational age human fetal testes. The scarcity of available third trimester human fetal tissue has, however prevented a complete examination throughout the gestational period and the cell specific expression of follistatin and beta A- and beta B-subunit mRNAs are currently unknown at any gestational age. In the present study, this gap is filled and report mRNA expression patterns of inhibin/activin subunits in mid- and late-gestational age (21-33 wk) human fetal testes and testicular duct system. We also report the first examination of follistatin mRNA signals in the human fetal gonad is also resent in both tubular and interstitial cells, and beta B-subunit mRNA is expressed in seminiferous tubules, in mid- and late-gestational age human fetal testes. Inhibin/activin beta A-subunit mRNA was detected in the interstitial cells of remarkably well preserved mid (21 and 22 wk) and late (29 wk) gestational age testes, and is the only activin-system factor mRNA also expressed in tissue of the duct system of the testis (smooth muscle cells of the epididymis). Follistatin mRNA signal was equal to background levels in testicular and duct tissues at all ages examined. These cell specific expression patterns suggest prominent and possibly differential roles for the inhibins and activins, unopposed by gonadal follistatin, in the human fetal male reproductive system.

背景与目标： 已在妊娠早期至中期人类胎儿睾丸中检查了抑制素/激活素亚基 (α，β A和 β B) 免疫反应蛋白定位模式和细胞类型特异性抑制素 α 亚基mRNA表达。妊娠晚期人类胎儿组织的缺乏，但是在整个妊娠期间都无法进行完整的检查，并且卵泡抑素和 β a和 β B亚基mrna的细胞特异性表达目前在任何胎龄都是未知的。在本研究中，填补了这一空白，并报告了孕中期和晚期 (21-33周) 人类胎儿睾丸和睾丸导管系统中抑制素/激活素亚基的mRNA表达模式。我们还报告了人类胎儿性腺中卵泡抑素mRNA信号的首次检查，在肾小管和间质细胞中也是如此，并且 β B亚基mRNA在生精小管中表达，在胎龄中期和晚期人类胎儿睾丸。在保存良好的中期 (21和22周) 和晚期 (29周) 胎龄睾丸的间质细胞中检测到抑制素/激活素 β-亚基mRNA，并且是唯一的激活素系统因子mRNA也在睾丸的导管系统 (附睾的平滑肌细胞) 的组织中表达。在所有年龄段的睾丸和导管组织中，卵泡抑素mRNA信号均等于背景水平。这些细胞特异性表达模式表明，在人类胎儿男性生殖系统中，抑制素和激活素 (不受性腺卵泡抑素的影响) 具有显着的作用，并且可能具有不同的作用。

BACKGROUND & AIMS: :Azoospermia is a condition defined as the absence of spermatozoa in the ejaculate, but the testicular phenotype of men with azoospermia may be very variable, ranging from full spermatogenesis, through arrested maturation of germ cells at different stages, to completely degenerated tissue with ghost tubules. Hence, information regarding the cell-type-specific expression patterns is needed to prioritise potential pathogenic variants that contribute to the pathogenesis of azoospermia. Thanks to technological advances within next-generation sequencing, it is now possible to obtain detailed cell-type-specific expression patterns in the testis by single-cell RNA sequencing. However, to interpret single-cell RNA sequencing data properly, substantial knowledge of the highly sophisticated data processing and visualisation methods is needed. Here we review the complex cellular structure of the human testis in different types of azoospermia and outline how known genetic alterations affect the pathology of the testis. We combined the currently available single-cell RNA sequencing datasets originating from the human testis into one dataset covering 62,751 testicular cells, each with a median of 2637 transcripts quantified. We show what effects the most common data-processing steps have, and how different visualisation methods can be used. Furthermore, we calculated expression patterns in pseudotime, and show how splicing rates can be used to determine the velocity of differentiation during spermatogenesis. With the combined dataset we show expression patterns and network analysis of genes known to be involved in the pathogenesis of azoospermia. Finally, we provide the combined dataset as an interactive online resource where expression of genes and different visualisation methods can be explored ( https://testis.cells.ucsc.edu/ ).

背景与目标： : 无精子症是一种疾病，定义为射精中没有精子，但是患有无精子症的男性的睾丸表型可能非常多变，从完全的精子发生到不同阶段的生殖细胞的停滞成熟，再到完全变性的组织与鬼小管。因此，需要有关细胞类型特异性表达模式的信息，以优先考虑导致无精子症发病的潜在致病变异。由于下一代测序技术的进步，现在可以通过单细胞RNA测序在睾丸中获得详细的细胞类型特异性表达模式。但是，要正确解释单细胞RNA测序数据，需要对高度复杂的数据处理和可视化方法有足够的了解。在这里，我们回顾了不同类型的无精子症中人类睾丸的复杂细胞结构，并概述了已知的遗传改变如何影响睾丸的病理。我们将源自人类睾丸的当前可用的单细胞RNA测序数据集合并为一个数据集，覆盖62,751个睾丸细胞，每个具有2637个转录本的中位数。我们展示了最常见的数据处理步骤有什么效果，以及如何使用不同的可视化方法。此外，我们计算了假时间的表达模式，并显示了如何使用剪接速率来确定精子发生过程中的分化速度。通过组合数据集，我们显示了已知与无精子症发病机理有关的基因的表达模式和网络分析。最后，我们将组合数据集作为交互式在线资源提供，可以在其中探索基因的表达和不同的可视化方法 (https://testis.cells.ucsc.edu/ )。

BACKGROUND & AIMS: :In mouse fetal gonads, sex differentiation begins at 10.5-11.5 days postcoitum (dpc). With XY gonads of 12.5 dpc, cord-like structures are visible and stromal cells migrate from adjacent mesonephros, unlike in XX gonads. However, the migrated mesonephric cells, except for the endothelial cells, have not been specifically identified because they have not expressed differentiation markers over the course of organ coculture in previous experiments. In this study, we have for the first time succeeded in isolating only the mesonephric cells that migrate into the XY gonad from the mesonephros with alive and then cultured these cells in vitro through the use of an organ coculture system using EGFP-transgenic mice and a FACS Vantage. The migrated and isolated cells were used for morphological and molecular characterization. The migrated mesonephric cells contained three cell forms; a sharp cell form, a round cell form, and a cluster-forming cell. The sharp cells have the characters of peritubular myoid cells. The round cells and cluster-forming cells have the potential to differentiate into Leydig cells, as some of them are 3beta-HSD-positive. In in vitro culture of migrated mesonephric cells, the cluster-forming cells proliferated well and then differentiated into round cells, suggesting that the cluster-forming cells may be stem or precursor cells for the round cells. Thus, our findings provide important information related to the migration and differentiation of migrated mesonephric cells in the XY gonad.

背景与目标： : 在小鼠胎儿性腺中，性别分化开始于coitum后10.5-11.5天 (dpc)。与12.5 dpc的XY性腺不同，脐带样结构是可见的，并且基质细胞从相邻的中肾迁移，这与XX性腺不同。但是，除内皮细胞外，迁移的中肾细胞尚未得到明确鉴定，因为它们在先前的实验中在器官共培养过程中没有表达分化标记。在这项研究中，我们首次成功地仅从中肾存活的中肾细胞中分离出了迁移到XY性腺中的中肾细胞，然后通过使用EGFP转基因小鼠的器官共培养系统在体外培养这些细胞和FACS优势。迁移和分离的细胞用于形态和分子表征。迁移的中肾细胞包含三种细胞形式; 尖锐的细胞形式，圆形细胞形式和簇形成细胞。尖锐细胞具有肾小管周围肌样细胞的特征。圆形细胞和簇形成细胞具有分化为Leydig细胞的潜力，因为其中一些细胞是3β-hsd阳性。在迁移的中肾细胞的体外培养中，簇形成细胞增殖良好，然后分化为圆形细胞，这表明簇形成细胞可能是圆形细胞的干细胞或前体细胞。因此，我们的发现提供了与XY性腺中迁移的中肾细胞的迁移和分化有关的重要信息。

BACKGROUND & AIMS: :Gene regulation was long predicted to play a vital role in speciation and species divergence. Only recently with the advent of new technologies, however, has it been possible to address the question of the relative contributions of different mechanisms of gene expression to the evolution of phenotypic diversity. Here we broaden the question and ask whether microRNAs, a large class of small regulatory RNAs, play a role in reproductive isolation between species by contributing to hybrid male sterility. MicroRNAs from the testes of clawed frogs (Xenopus) were extracted and the expression profiles of sterile hybrids were compared with males of a parental species. Hybrid testes were largely microRNA-depleted relative to those of nonhybrids, and this pattern was validated with quantitative RT-PCR. A number of candidate differential microRNAs from this study have previously been described as testis-specific in the mouse, suggesting that microRNA structural conservation may be associated with functional retention.

背景与目标： : 长期以来，人们一直认为基因调控在物种形成和物种分化中起着至关重要的作用。然而，直到最近，随着新技术的出现，才有可能解决基因表达的不同机制对表型多样性进化的相对贡献的问题。在这里，我们扩大了问题的范围，并询问microRNAs (一大类小型调节rna) 是否通过促进杂种雄性不育而在物种之间的生殖隔离中发挥作用。从爪蛙 (非洲爪蟾) 的睾丸中提取microrna，并将不育杂种的表达谱与亲本物种的雄性进行比较。相对于非杂种，杂种睾丸在很大程度上耗尽了microRNA，并且该模式已通过定量rt-pcr验证。先前已将本研究中的许多候选差异microRNA描述为小鼠睾丸特异性，这表明microRNA结构保守性可能与功能保留有关。

BACKGROUND & AIMS: :Tributyltin (TBT) is known to disrupt the development of reproductive organs, thereby reducing fertility. The aim of this study was to evaluate the acute toxicity of TBT on the testicular development and steroid hormone production. Immature (3-week-old) male mice were given a single administration of 25, 50, or 100 mg/kg of TBT by oral gavage. Lumen formation in seminiferous tubule was remarkably delayed, and the number of apoptotic germ cells found inside the tubules was increased in the TBT-exposed animals, whereas no apoptotic signal was observed in interstitial Leydig cells. Reduced serum testosterone concentration and down-regulated expressions of the mRNAs for cholesterol side-chain cleavage enzyme (P450scc), 17alpha -hydroxylase/C(17-20) lyase (P450(17alpha)), 3beta -hydroxysteroid-dehydrogenase (3beta -HSD), and 17beta -hydroxysteroid-dehydrogenase (17beta -HSD) were also observed after TBT exposure. Altogether, these findings demonstrate that exposure to TBT is associated with induced apoptosis of testicular germ cells and inhibition of steroidogenesis by reduction in the expression of steroidogenic enzymes in interstitial Leydig cells. These adverse effects of TBT would cause serious defects in testicular development and function.

背景与目标： : 已知三丁基锡 (TBT) 会破坏生殖器官的发育，从而降低生育能力。这项研究的目的是评估TBT对睾丸发育和类固醇激素产生的急性毒性。通过口服灌胃给未成熟 (3周龄) 的雄性小鼠单次施用25、50或100 mg/kg的TBT。在暴露于TBT的动物中，生精小管中的管腔形成显着延迟，并且在小管内发现的凋亡生殖细胞数量增加，而在间质Leydig细胞中未观察到凋亡信号。降低血清睾酮浓度，降低胆固醇侧链裂解酶 (P450scc) 、17α-羟化酶/C(17-20) 裂解酶 (P450 (17α)) 、3β-羟基类固醇脱氢酶 (3β-hsd) 的mrna表达，TBT暴露后还观察到17β-羟基类固醇脱氢酶 (17β-hsd)。总之，这些发现表明，暴露于TBT与诱导的睾丸生殖细胞凋亡和通过减少间质Leydig细胞中类固醇生成酶的表达而抑制类固醇生成有关。TBT的这些不良影响将导致睾丸发育和功能的严重缺陷。

BACKGROUND & AIMS: Several recent studies have suggested that testicular germ cell tumors express high levels of wild-type p53 protein. To clarify and confirm this unexpected result, we have investigated seminomatous and nonseminomatous germ cell tumors at the genomic, mRNA, and protein levels. Thirty-five tumors were examined for p53 overexpression using antibodies directed against the p53 (PAb1801, PAb240, and CM1), mdm2 (IF2), and p21Waf1/Clp1 (EA10) proteins. Thirty-two tumors were screened for p53 mutations by single-strand conformation polymorphism analysis. Eighteen tumors were screened with a functional assay that tests the transcriptional competence of human p53 protein expressed in yeast. On frozen sections, 100, 65, 35, 73, and 0% of tumors reacted with the CM1, PAb240, PAb1801, IF2, and EA10 antibodies, respectively. No p53 mutations were detected by single-strand conformation polymorphism or by functional assay. The fact that many tumors overexpress wild-type p53 but not mdm2 rules out mdm2 overexpression as a general explanation for the presence of wild-type p53 in these tumors. The absence of p21 overexpression suggests that p53 may be unable to activate transcription of critical target genes, which may explain why the presence of wild-type p53 is tolerated in this tumor type, although the mechanism for this transcriptional inactivity remains to be established.

背景与目标： 最近的一些研究表明，睾丸生殖细胞肿瘤表达高水平的野生型p53蛋白。为了澄清和确认这一意外结果，我们在基因组，mRNA和蛋白质水平上研究了精原细胞和非精原细胞生殖细胞肿瘤。使用针对p53 (PAb1801，PAb240和CM1)，mdm2 (IF2) 和p21Waf1/Clp1 (EA10) 蛋白的抗体检查了35个肿瘤的p53过表达。通过单链构象多态性分析筛选了32个肿瘤的p53突变。用功能测定法筛选了18个肿瘤，该测定法测试了酵母中表达的人p53蛋白的转录能力。在冷冻切片上，100、65、35、73和0% 的肿瘤分别与CM1、PAb240、PAb1801、IF2和EA10抗体反应。通过单链构象多态性或功能分析未检测到p53突变。许多肿瘤过表达野生型p53而非mdm2的事实排除了mdm2过表达作为这些肿瘤中野生型p53存在的一般解释。p21过表达的缺乏表明p53可能无法激活关键靶基因的转录，这可以解释为什么在这种肿瘤类型中可以耐受野生型p53的存在，尽管这种转录不活跃的机制仍有待建立。

BACKGROUND & AIMS: OBJECTIVE:To investigate histological changes in the contralateral testis of rats with unilateral testicular torsion and the protective effects of nitric oxide (NO) on possible damage. MATERIAL AND METHODS:Twenty-eight prepubertal male Sprague-Dawley rats were divided into four equal groups. Group 1 underwent a sham operation of the right testis under general anaesthesia. Group 2 underwent a similar operation but the right testis was rotated 720 degrees clockwise for 6 h, maintained by fixing the testis to the scrotum, and saline infused during the procedure. Group 3 underwent similar torsion but L-arginine methyl ester (a precursor of NO) was infused during the procedure. In Group 4, NG-nitro-L-arginine-methyl ester, a NO synthase inhibitor, was infused separately during the administration of L-arginine methyl ester and torsion. All the left (untwisted) testes were removed from rats 21 days after surgery and evaluated histologically, assessing seminiferous tubule diameter, loss of sperm and spermatids, loss of germ cell layers, disarray of germ cell layers, rupture of tubules, Leydig cell proliferation and reaction in the ruptured tubules, and oedema. RESULTS:There was a significant difference in the indicators of histological damage between groups 2 and 4 and groups 1 and 3, except for the Leydig cell reaction in the ruptured tubules and oedema. The damage was significantly less in group 3 than in groups 2 and 4. CONCLUSION:These results suggest that long-term histopathological changes in the contralateral testes are important after unilateral testicular torsion and that NO has a protective effect on the contralateral testis.

背景与目标：

BACKGROUND & AIMS: :In situ alterations of DNA methylation were studied between 14 d postcoitum and 4 d postpartum in Sertoli cells and germ cells from mouse testis, using anti-5-methylcytosine antibodies. Compared to cultured fibroblasts, Sertoli cells display strongly methylated juxtacentromeric heterochromatin, but hypomethylated chromatids. Germ cells always possess hypomethylated heterochromatin, whereas their euchromatin passes from a demethylated to a strongly methylated status between days 16 and 17 postcoitum. This hypermethylation occurs in the absence of DNA replication, germ cells being blocked in the G(0)-G(1) phase from day 15 postcoitum to birth. The DNA hypermethylation of germ cells is maintained until birth and could be visualized on both chromatids of metaphase chromosomes at the first postpartum cell division. Subsequently, the DNA hypermethylation is lost semiconservatively, being replaced by a methylation pattern recalling the typical fibroblast pattern. These alterations of DNA methylation follow a strict chronology, are chromosome structure and cell-type dependent, and may underlie profound changes of genome function.

背景与目标： : 使用anti-5-methylcytosine抗体研究了小鼠睾丸支持细胞和生殖细胞在产后14 d和产后4 d之间DNA甲基化的原位改变。与培养的成纤维细胞相比，Sertoli细胞显示出强烈的甲基化的间生异染色质，但低甲基化的染色单体。生殖细胞始终具有低甲基化的异染色质，而它们的常染色质在第16至17天之间从去甲基化状态转移到强烈甲基化状态。这种高甲基化发生在没有DNA复制的情况下，生殖细胞从出生后第15天到出生在G(0)-G(1) 阶段被阻断。生殖细胞的DNA高甲基化一直维持到出生，并且可以在产后第一次细胞分裂时在中期染色体的两个染色单体上观察到。随后，DNA超甲基化被半保守地丢失，被甲基化模式取代，使其回想起典型的成纤维细胞模式。DNA甲基化的这些改变遵循严格的时间顺序，是染色体结构和细胞类型依赖性的，并且可能是基因组功能深刻变化的基础。

BACKGROUND & AIMS: :We have analyzed 25 patients with primary testicular large-cell non-Hodgkin's lymphoma managed at our institution from 1972-1998. The median age was 69 years, with bilateral testicular involvement in 16%. The disease stage was I in 56%, II in 32%, and IV in 12%. Twenty-four patients received further therapy after orchiectomy, including chemotherapy in 18 and radiation therapy in 11 (encompassing regional nodes in 8 and the contralateral testis in 6), with 5 patients receiving both modalities. The complete remission rate was 88%, but a continuous pattern of recurrence is evident up to 10 years, when only 23% of patients are predicted to be in ongoing remission. The dominant sites of first failure were extranodal (91%), with prominent involvement of the contralateral testis and cerebral parenchyma. The 10-year overall survival rate is 32%, and the median overall survival is 4.4 years. Within the entire cohort, adverse prognostic factors for treatment failure were serum albumin < or = to 3.5 g/dL (P = 0.02), advanced age, advanced stage, and lack of anthracycline-containing chemotherapy (each P < or = to 0.3). Among patients with locoregional disease, albumin < or = to 3.5 g/dL (P = 0.08), no anthracycline-containing chemotherapy (P = 0.15), and fewer than 6 cycles of chemotherapy (P = 0.03) remained predictive. Based on this analysis, we are prospectively evaluating a treatment program for patients with testicular non-Hodgkin's large-cell lymphoma comprising (1) 6 cycles of anthracycline-based chemotherapy, (2) prophylactic radiation therapy to the contralateral testis, and (3) central nervous system prophylaxis with both intrathecal chemotherapy and systemic high-dose methotrexate.

背景与目标： : 我们分析了1972-1998年在我们机构管理的25例原发性睾丸大细胞非霍奇金淋巴瘤患者。中位年龄69岁，16% 双侧睾丸受累。疾病阶段为56% 年I，32% 年II，12% 年IV。24例患者在睾丸切除术后接受了进一步的治疗，包括18例化疗和11例放疗 (包括8例区域淋巴结和6例对侧睾丸)，其中5例接受了两种方式。完全缓解率是88% 的，但是当预测只有23% 的患者处于持续缓解期时，持续10年的复发模式是明显的。首次失败的主要部位是结外 (91%)，对侧睾丸和脑实质明显受累。10年总生存率为32%，中位总生存率为4.4年。在整个队列中，治疗失败的不良预后因素是血清白蛋白 <或 = 3.5g/dL (P = 0.02)，高龄，晚期和缺乏含蒽环类药物的化疗 (每个P <或 = 0.3)。在局部区域疾病患者中，白蛋白 <或 = 3.5g/dL (P = 0.08)，没有含蒽环类药物的化疗 (P = 0.15) 和少于6个周期的化疗 (P = 0.03) 仍然是可预测的。基于此分析，我们正在前瞻性评估睾丸非霍奇金大细胞淋巴瘤患者的治疗计划，包括 (1) 6个周期的基于蒽环类药物的化疗，(2) 对侧睾丸的预防性放射治疗，(3) 鞘内化疗和全身大剂量甲氨蝶呤预防中枢神经系统。

BACKGROUND & AIMS: BACKGROUND:The strength of the association between undescended testis and testicular cancer varies considerably across studies. Here we report the effect of various classifications of self-reported history of undescended testis and different data sources on the estimates of the risk of testicular cancer from a case-control study. METHODS:We performed a population-based case-control study including 269 testicular cancer cases and 797 controls matched on age and region. Medical history was assessed by interviews (index persons) and mailed questionnaires (mothers). We used conditional logistic regression to calculate odds ratios (OR) and kappa coefficients to assess agreement between different sources of information. RESULTS:Odds ratios for testicular cancer ranged between 2.4 and 5.4 based on the sons' self-reports and between 1.1 and 1.9 based on the mothers' reports. The agreement between the sons and mothers on undescended, gliding or retractile testis was fair (kappa 0.53) and was good when these conditions were treated by surgery (kappa 0.89). The rating of a history of undescended testis by two urologists was fair (kappa 0.54). CONCLUSIONS:The questionnaire design, the classifications of undescended testis and data sources have an important impact on the OR for the association of undescended testis and testicular cancer. These factors may partially explain the heterogeneity of the OR for this association in case-control studies relying on self-reports.

背景与目标：

BACKGROUND & AIMS: :We have characterized the expression of MYCL2, an intronless X-linked gene related to MYCL1. RNase protection analysis of a panel of human normal and tumor tissues has revealed that MYCL2 is expressed almost exclusively in human adult normal testis; much lower levels of transcript were detected in one human lung adenocarcinoma. No MYCL2 transcript was found in human testis RNA obtained from second trimester fetuses. This observation suggests a germ cell rather than somatic cell origin of the transcript and possible developmental regulation of MYCL2. Northern blot analysis of poly(A)+ RNA from adult human normal testis with an antisense riboprobe revealed a transcript of approximately 4.8-kb, which is in agreement with the size predicted from the MYCL2 nucleotide sequence. Antisense transcripts were found spanning regions of MYCL2 corresponding to all three exons of MYCL1. No sizable open reading frame was seen for the MYCL2 antisense transcripts suggesting that they may represent either regulatory sequences or an intron of a gene encoded by the complementary strand. RNase protection assays and the 5' RACE protocol (Rapid Amplification of cDNA Ends) were used to address the localization of the transcription start site of the MYCL2 sense transcript and different putative promoters and transcription regulatory elements have been identified.

背景与目标： : 我们已经表征了MYCL2的表达，MYCL2是与mycl1相关的无内含子X连锁基因。对一组人类正常和肿瘤组织的RNase保护分析表明，MYCL2几乎仅在人类成人正常睾丸中表达; 在一种人肺腺癌中检测到的转录本水平要低得多。在从妊娠中期胎儿获得的人睾丸RNA中未发现MYCL2转录本。此观察结果表明转录本的生殖细胞而不是体细胞起源以及mycl2的可能发育调控。用反义核糖探针对来自成人正常睾丸的poly(A)+ RNA进行的Northern印迹分析显示，转录物约为4.8-kb，这与从MYCL2核苷酸序列预测的大小一致。发现反义转录本跨越MYCL2的区域，对应于mycl1的所有三个外显子。对于MYCL2反义转录本，没有看到相当大的开放阅读框，表明它们可能代表由互补链编码的基因的调控序列或内含子。RNase保护试验和5' RACE方案 (cDNA末端的快速扩增) 用于解决MYCL2有义转录本的转录起始位点的定位，并且已经鉴定出不同的推定启动子和转录调控元件。

BACKGROUND & AIMS: PURPOSE:Cancer-testis (CT) antigens are often expressed in a proportion of tumors of various types. Their restricted normal tissue expression and immunogenicity make them potential targets for immunotherapy. CABYR is a calcium-binding tyrosine phosphorylation-regulated fibrous sheath protein initially reported to be testis specific and subsequently shown to be present in brain tumors. This study was to determine whether CABYR is a novel CT antigen in lung cancer. EXPERIMENTAL DESIGN:mRNA expression of CABYR-a/b (combination of CABYR-a and CABYR-b) and CABYR-c was examined in 36 lung cancer specimens, 14 cancer cell lines, and 1 normal cell line by conventional and real-time reverse transcription-PCR. Protein expression of CABYR was analyzed in 50 lung cancer tissues by immunohistochemistry. Antibodies specific to CABYR were analyzed in sera from 174 lung cancer patients and 60 healthy donors by ELISA and Western blot. RESULTS:mRNA expression of CABYR-a/b and CABYR-c was observed, respectively, in 13 and 15 of 36 lung cancer tissues as well as in 3 and 5 of 14 cancer cell lines, whereas neither of them was observed in adjacent noncancerous tissues or the normal cell line. Protein expression of CABYR-a/b and CABYR-c was observed, respectively, in 20 and 19 of 50 lung cancer tissues. IgG antibodies specific to CABYR-a/b and CABYR-c were detected, respectively, in 11% and 9% of sera from lung cancer patients but not from the 60 healthy donors. CONCLUSION:CABYR is a novel CT antigen in lung cancer and may be a promising target for immunotherapy for lung cancer patients.

背景与目标：

BACKGROUND & AIMS: :The lactate dehydrogenase (LDH) isoenzyme pattern of prostate and of testis of 27 wild animals showed that in several species more than 5 isoenzymes are detected, with electrophoretic mobilities different to those found in humans. The LDH-X band, found in testis from mature humans is also observed in the testis of wild animals. However, in several species more than one LDH-X is found. The results obtained demonstrate their usefulness in phylogeny. The prostate gland and testis of the chimpanzee show the greatest resemblance to man. Histological examination of the prostate glands seems to correlate with the phylogenetical classification of the mammals studied.

背景与目标： : 27种野生动物的前列腺和睾丸的乳酸脱氢酶 (LDH) 同工酶模式表明，在几种物种中检测到5种以上的同工酶，其电泳迁移率与人类不同。在野生动物的睾丸中也观察到在成熟人类的睾丸中发现的ldh-x带。但是，在几种物种中发现了一个以上的ldh-x。获得的结果证明了它们在系统发育中的有用性。黑猩猩的前列腺和睾丸与人类最相似。前列腺的组织学检查似乎与所研究哺乳动物的系统发育分类有关。