bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of testicular toxicology: A synopsis and discussion of the recommendations proposed by the Society of Toxicologic Pathology
Authors: Creasy Dianne M. 
Published: October 2003

AbstractBackground: Detection of chemically induced effects on male fertility and on testicular spermatogenesis in particular, has become of increasing concern. More stringent regulatory guidelines, introduced by ICH, EPA and OECD (Table 1) have raised the awareness of toxicologists and pathologists for the need to conduct sensitive and careful evaluation of the male reproductive tract for potential toxic effects of administered compounds. With it has come confusion and in many cases, inappropriate procedures, often based on misunderstanding of what is required and on inadequate understanding of spermatogenesis. This article summarizes and discusses the main recommendations recently proposed by the Society of Toxicologic Pathology on recommended approaches for the evaluation of testicular and epididymal toxicity [Lanning LL, Creasy DM, Chapin RE, Mann PC, Barlow NJ, Regan KS, Goodman DG. Toxicologic Pathology 30:518–531, 2002]. The major recommendations are:

Use sexually mature animals to evaluate effects on spermatogenesis.
Sample left and right testes and epididymides and record organ weights.
Use modified Davidson's fixative to fix testes from all species from studies of 13 wks duration and less.
Examine transverse sections of the testes (including part of the rete), and longitudinal sections of the epididymides.
Embed tissues in paraffin wax.
For rodent studies up to 28 days, examine periodic acid‐Schiff's‐hematoxylin stained sections. For all other studies examine hematoxylin and eosin stained sections.
Microscopic evaluation of the testis should be a qualitative evaluation carried out with an awareness of the spermatogenic cycle. Quantitative procedures are inappropriate for screening studies.
Nomenclature and grading of findings for spermatogenic disturbances will vary on a case by case basis
Birth Defects Res B 68:408–415, 2003. © 2003 Wiley‐Liss, Inc.
Vaults bind directly to microtubules via their caps and not their barrels
Authors: Eichenmüller Bernd , Kedersha Nancy , Solovyeva Elena , Everley Patrick , Lang Jennifer , Himes Richard H. , Suprenant Kathy A. 
Published: October 2003

AbstractVaults are large (13 Mda) ribonucleoprotein particles that are especially abundant in multidrug resistant cancer cells and have been implicated in nucleocytoplasmic drug transport. To understand how these large barrel‐shaped complexes are transported through the cytosol, we examined the association of vaults with microtubules both in vitro and in vivo. Within cells, a subpopulation of vaults clearly associates with microtubules, and these vaults remain associated with tubulin dimers/oligomers when microtubules are disassembled by nocodazole treatment. In vitro, a microtubule‐pull down assay using highly purified rat vaults and reassembled microtubules reveals that vaults exhibit concentration‐dependent binding to microtubules that does not require the carboxyl terminal end of tubulin. Remarkably, negative staining for electron microscopy reveals that vault binding to microtubules is mediated by the vault caps; more than 82% of bound vaults attach to the microtubule lattice with their long axes perpendicular to the long axis of the microtubule. Five to six vault particles were bound per micron of microtubule, with no crosslinking of microtubules observed, suggesting that only one end of the vault can bind microtubules. Taken together, the data support the model of vaults as barrel‐shaped containers that transiently interact with microtubules. Cell Motil. Cytoskeleton 56:225–236, 2003. © 2003 Wiley‐Liss, Inc.
LIS1 association with dynactin is required for nuclear motility and genomic union in the fertilized mammalian oocyte
Authors: Payne Christopher , St. John Justin C. , Ramalho‐Santos João , Schatten Gerald 
Published: October 2003

AbstractMutations in the human LIS1 gene cause the devastating brain disorder lissencephaly. LIS1 also regulates microtubule dynamics; it interacts with the molecular motor cytoplasmic dynein and its cofactor dynactin, and is necessary for neuronal migration. Recently, LIS1 has been suggested to mediate pronuclear migration during fertilization. Here we use rhesus monkey and bovine oocytes, as well as pronucleate‐stage bovine zygotes, to determine: Lis1 RNA expression using reverse transcription‐polymerase chain reaction; LIS1 protein association with dynactin using immunoprecipitation, Western blot analysis, and immunocytochemistry; and LIS1 function in mediating genomic union using antibody transfection. We find that Lis1 RNA expression increases during fertilization, that LIS1 and dynactin subunit p150/Glued co‐immunoprecipitate and co‐localize to pronuclear surfaces, and that anti‐LIS1 antibodies transfected into zygotes dramatically inhibit pronuclear migration and apposition. LIS1 is, therefore, essential to mediate genomic union in a process that involves the dynein‐dynactin complex. These results shed light on an additional role for LIS1 and raise implications for human reproduction. Cell Motil. Cytoskeleton 56:245–251, 2003. © 2003 Wiley‐Liss, Inc.
Increased expression of matrix metalloproteinase‐2 and tissue inhibitor of metalloproteinase‐2 is correlated with poor prognostic variables in patients with thymic epithelial tumors
Authors: Sogawa Ken‐ichi , Kondo Kazuya , Fujino Haruhiko , Takahashi Yuji , Miyoshi Takanori , Sakiyama Shoji , Mukai Kiyoshi , Monden Yasumasa 
Published: October 2003

AbstractBACKGROUNDA distinction between noninvasive, invasive, and metastatic thymoma on the basis of the cytologic features is difficult. The current study investigated whether the expression of MMP and TIMP was correlated with tumor invasiveness and prognosis in patients with thymoma.METHODSTumor tissue samples were obtained from 42 patients with thymic epithelial tumors between 1974 and 2001 at Tokushima University Hospital. Three‐micrometer‐thick, formalin‐fixed, paraffin‐embedded tissue sections were immunostained using specific antibodies against MMP‐2, MMP‐9, TIMP‐1, and TIMP‐2.RESULTSMMP‐2 expression was detected in 30 tumors (71%), and TIMP‐2 expression was detected in 31 tumors (74%). MMP‐9 expression was detected in 22 of 36 tumors (61%), and TIMP‐1 expression was detected in only 7 tumors (19%). MMP‐2 and TIMP‐2 expression levels were very low (10% and 0%, respectively) in noninvasive tumors but were very high (91% and 97%, respectively) in invasive tumors. In thymic epithelial tumors, the more progressive the clinical stage of tumor, the higher the strongly positive rate of MMP‐2 and TIMP‐2 expression. There was no correlation between positivity for MMP‐9 and stage. Twenty‐five percent of Type AB thymomas and 50% of Type B1 thymomas expressed MMP‐2 and TIMP‐2. Most of Type A, Type B2, Type B3, and Type C thymomas expressed MMP‐2 and TIMP‐2. There were significant differences in disease‐free survival at 5 years between patients without and with MMP‐2 expression (91% vs. 55%, respectively) and patients without and with TIMP‐2 expression (100% vs. 53%, respectively).CONCLUSIONSMMP‐2 and TIMP‐2 are key enzymes for invasiveness of thymic epithelial tumors. The expression of these proteins can predict a poor outcome in patients with thymoma. Cancer 2003. © 2003 American Cancer Society.
Clinical experience with intravenous estramustine phosphate, paclitaxel, and carboplatin in patients with castrate, metastatic prostate adenocarcinoma
Authors: Solit David B. , Morris Michael , Slovin Susan , Curley Tracy , Schwartz Lawrence , Larson Steven , Kattan Michael W. , Hartley‐Asp Beryl , Scher Howard I. , Kelly W. Kevin 
Published: October 2003

AbstractBACKGROUNDThe combination of paclitaxel, oral estramustine phosphate (EMP), and carboplatin (TEC) has shown antitumor activity in patients with castrate, metastatic prostate carcinoma. To improve the therapeutic efficacy and reduce the toxicity of TEC, the authors substituted intravenous (i.v.) EMP for oral EMP based on single‐agent studies demonstrating an improved safety profile with i.v. EMP.METHODSPatients with progressive, castrate, metastatic prostate carcinoma were treated with up to 6 4‐week cycles of i.v. EMP (500–1500 mg/m2 per week), paclitaxel (100 mg/m2 per week), and carboplatin (target area under the curve = 6 mg/mL every 4 weeks).RESULTSThirty patients were treated in 6 dose cohorts. Deep venous thrombosis occurred in 5 of 30 patients (17%). Other common Grade 3/4 (according to National Cancer Institute Common Toxicity Criteria) toxicities included hepatic toxicity (23%) and leukopenia (24%). Posttherapy prostate specific antigen declines > 50% were seen in 18 of 30 patients (60%), and declines > 80% were seen in 15 of 30 patients (50%). Eleven of 17 patients (65%) with measurable soft tissue disease achieved a partial response. Four of 27 patients (15%) with osseous metastases demonstrated improvement on bone scan.CONCLUSIONSIntravenous EMP was administered safely with paclitaxel and carboplatin and produced clinical outcomes similar to the outcomes achieved with the TEC regimen. Substitution of i.v. EMP for the oral formulation was found to result in a lower incidence of severe nausea but increased hepatic toxicity. Cancer 2003. © 2003 American Cancer Society.
The 1999 patterns of care study of radiotherapy in localized prostate carcinoma
Authors: Lee W. Robert , Moughan Jennifer , Owen Jean B. , Zelefsky Michael J. 
Published: October 2003

AbstractBACKGROUNDThe objective of the current study was to provide descriptive information on a representative national sample of patients with prostate carcinoma who were treated with prostate brachytherapy (PB) in calendar year 1999.METHODSA random survey was conducted by the Patterns of Care Study in radiation oncology of 59 facilities (1 facility had no eligible patients) that treated patients with prostate carcinoma in 1999 in the United States. A weighted sample size of 36,496 patients with prostate cancer was included in the 1999 survey (unweighted sample size, 554 patients). The main measures were the clinical characteristics of men prior to treatment and the technical characteristics of PB. Patients were classified into three prognostic groups according to T stage, pretreatment prostate specific antigen (PSA) level, and Gleason score.RESULTSA weighted sample size of 13,293 patients (36%; unweighted sample size, 162 patients) was treated with PB. Compared with a weighted sample size of 23,203 patients (64%; unweighted sample size, 392 patients) was treated with external beam radiotherapy (EB), patients who received PB were significantly younger (mean age: PB group, 67.7 years; EB group, 70.8 years; P = 0.0006). The mean pretreatment PSA level for the PB group was lower compared with the EB group (9.9 ng/mL vs. 13.33 ng/mL; P = 0.0015). The prognostic groupings were more favorable for patients in the PB group compared with patients in EB group (P = 0.0365). The utilization of androgen deprivation therapy (ADT) in the PB group was similar to the utilization of ADT in the EB group (40.4% vs. 51.3%; P = 0.2282). The vast majority of men who were treated with PB received low‐dose‐rate, permanent sources (89%). Fifty‐four percent of men received PB monotherapy (PBM), and the remaining 46% were treated with EB in addition to PB (EBPB). The prognostic groupings were more favorable for patients in the PBM group compared with patients in the EBPB group (P = 0.0037). Of the men who were treated with low‐dose‐rate PB, 59% were treated with iodine‐125 (I‐125), and 41% were treated with palladium‐103 (Pd‐103). I‐125 was used more frequently in men who were treated with PBM, and Pd‐103 was used more frequently in men who were treated with EBPB. Postimplantation dosimetry was documented in 61.0% of men who were treated with low‐dose‐rate PB. Computed tomography imaging was used for 46.5% of men.CONCLUSIONSPB was used in 36% of men who were treated with radiotherapy nationally. The mean age of men who were treated with PB was younger than the population of men who were treated with EB alone. Nearly 50% of men who received PB also received EB. EB was used more frequently in men with higher‐risk disease. ADT was used in 40% of patients in the PB group. Techniques and prescription doses were consistent with published guidelines. Cancer 2003. © 2003 American Cancer Society.
Overexpression of thioredoxin reductase 1 regulates NF‐κB activation
Authors: Sakurai Atsuko , Yuasa Kouji , Shoji Yasuko , Himeno Seiichiro , Tsujimoto Masafumi , Kunimoto Manabu , Imura Nobumasa , Hara Shuntaro 
Published: October 2003

AbstractThioredoxin reductase (TrxR) is a flavoprotein that contains a C‐terminal penultimate selenocysteine (Sec) and has an ability to reduce thioredoxin (Trx), which regulates the activity of NF‐κB. To date, three TrxR isozymes, TrxR1, TrxR2, and TrxR3, have been identified. In the present study, we found that among these isozymes only TrxR1 was induced by tumor necrosis factor‐α (TNFα) in vascular endothelial cells. Furthermore, the overexpression of TrxR1 enhanced TNFα‐induced DNA‐binding activity of NF‐κB and NF‐κB‐dependent gene expression. The catalytic Sec residue of TrxR1, which is essential for reducing Trx, was required for this NF‐κB activation, and aurothiomalate, an inhibitor of TrxR, suppressed TNFα‐induced activation of NF‐κB and the expression of NF‐κB‐targeted proinflammatory genes such as E‐selectin and cyclooxygenase‐2. These results suggest that TrxR1 may act as a positive regulator of NF‐κB and may play an important role in the cellular inflammatory response. © J. Cell. Physiol. 198: 22–30, 2004© 2003 Wiley‐Liss, Inc.
Osteopontin modulates CD44‐dependent chemotaxis of peritoneal macrophages through G‐protein‐coupled receptors: Evidence of a role for an intracellular form of osteopontin
Authors: Zhu Baoqian , Suzuki Keiko , Goldberg Harvey A. , Rittling Susan R. , Denhardt David T. , McCulloch Christopher A.G. , Sodek Jaro 
Published: October 2003

AbstractExpression of osteopontin (OPN) by activated T‐cells and macrophages is required for the development of cell‐mediated inflammatory responses. Acting through integrin αvβ3 and CD44 receptors, OPN can promote chemoattraction and pro‐inflammatory cytokine expression by macrophages. In this study, we have used periotoneal macrophages from OPN−/, CD44−/−, and WT mice to study the relationship between OPN and CD44 in macrophage migration. Using confocal microscopy, we show that OPN co‐distributes with CD44 inside macrophages at cell edges and in cell processes in a mutually dependent manner. The existence of an intracellular form of OPN is supported by pulse‐chase studies in which a thrombin‐sensitive, phosphorylated protein immunoprecipitated with OPN antibodies is retained inside macrophages. In OPN−/− and CD44−/− macrophages, the absence of CD44 and OPN, respectively, is associated with the formation of fewer cell processes, reduced cell fusion required to form functional multinucleated osteoclasts in the presence of CSF‐1 and RANKL, and impaired chemotaxis. Whereas the chemotaxis of CD44−/− cells to various chemoattractants is almost completely abrogated, a differential effect is seen with the OPN−/− cells. Thus, OPN−/− cells migrate normally towards CSF‐1 but not towards fMLP and MCP‐1, which signal through G‐protein coupled receptors (GPCRs). That the GPCR‐mediated migration is dependent upon the level of cell‐surface CD44 is indicated by the reduced cell‐surface expression of CD44 in OPN−/− cells and a comparable impairment in the chemotaxis of CD44+/− cells. Although chemotaxis of OPN−/− cells could be rescued by an OPN substratum, or by addition of high levels of OPN in solution, no response is evident with physiological levels of OPN, indicating a requirement for the CD44‐associated intracellular OPN in CD44 cell‐surface expression. These studies indicate, therefore, that the level of cell surface CD44 is critical for GPCR‐mediated chemotaxis by peritoneal macrophages and suggest that a novel intracellular form of OPN may modulate CD44 activities involved in these processes. J. Cell. Physiol. 198: 155–167, 2004. © 2003 Wiley‐Liss, Inc.
Non‐hematopoietic human bone marrow contains long‐lasting, pluripotential mesenchymal stem cells
Authors: Suva Domizio , Garavaglia Guido , Menetrey Jacques , Chapuis Bernard , Hoffmeyer Pierre , Bernheim Laurent , Kindler Vincent 
Published: October 2003

AbstractMesenchymal stem cells (MSC) are considered as potential agents for reconstructive and gene‐targeting therapies since they differentiate into various cell‐lineages, exhibit an extended survival once injected into a host, and can easily be transfected with engineered DNA. MSC are essentially isolated from hematopoietic bone marrow (BM), a process that is rather invasive and may raise ethical concerns. In an attempt to find an alternative source, we evaluated whether non‐hematopoietic (nh)BM recovered from femoral heads of patients undergoing hip arthroplasty contained MSC. Ex vivo, 99% of nhBM cells were CD45+ leukocytes. After culture, leukocytes were replaced by a homogenous layer of adherent CD45− CD14− CD34− CD11b− CD90+ HLA‐ABC+ cells. Culture doubling time (mean = 4 days, range 1.6–6.7 days) was not correlated with patient age (27–81 years, n = 16). Amplified cultures supported long‐term hematopoiesis, and could be differentiated in vitro into adipocytes and chondrocytes. Moreover, a small fraction of nhBM cells spontaneously expressed MyoD1 and formed myotubes, suggesting that myogenic differentiation also occurred. nhBM contained clonogenic cells whose frequency (1/13,000), doubling time (2.1 days), and maximal amplification (up to 106‐fold) were not age‐related. All 14 clones analyzed (from five patients, ages 27–78 years) differentiated into at least one mesenchymal lineage, and 66% were bipotential (n = 8/12), or tripotential (n = 2/3). In conclusion, nhBM contains pluripotential mesenchymal progenitors which are similar to hematopoietic BM‐derived MSC, and whose biological functions are not altered by aging. Furthermore, if MSC‐based therapies hold their promises, nhBM may become the source of choice for responding to the increasing demand for MSC. J. Cell. Physiol. 198: 110–118, 2004. © 2003 Wiley‐Liss, Inc.
Electron and light microscopic study of various glands and the secretions released into the environment by the turbellarian Urastoma cyprinae
Authors: Bataller Erick E. , Boghen Andrew D. , Burt Michael D.B. 
Published: October 2003

AbstractThe turbellarian Urastoma cyprinae (Graff) occurs on the gills of various bivalve species including the mussel Mytilus galloprovinciallis, where it is known to cause serious damage. More recently, it has been shown that the worms are strongly attracted to the gill of the American oyster (Crassostrea virginica) and are capable of inducing changes to the composition of proteolytic enzymes of the host mucus. Such changes may be attributable to secretory products released by the worms. Mucous glands (11–18 μm in diameter) produce minute spherules (0.7–0.9 μm in diameter) tightly bound together. The glands occupy ∼20% of the body volume and are the most voluminous secretory organs in the worm. The smaller rhabdoid glands are unevenly distributed throughout the peripheral parenchyma and contain secretory granules of 0.35–1.2 μm in diameter. The latter occur most prominently along the distal margins of the epidermis. The frontal pole of U. cyprinae consists of a complex assembly of mucous and rhabdoid gland cells as well as other glandular structures. Collectively, these bodies release their contents to the outside via narrow gland necks. The overall organization is consistent with the frontal gland previously described for other free‐living turbellarians, including other rhabdocoels. A variety of secretory products, displaying variations in staining properties, have likewise been identified in association with the body wall from other regions of the worm. This work attempts to gain a better appreciation of the secretory structures associated with the worm tegument, focusing primarily on the widespread mucous and rhabdoid glands. The secretions play a role in host‐parasite interactions. J. Morphol. 258:307–316, 2003. © 2003 Wiley‐Liss, Inc.
Sertoli cells in the testis of caecilians, Ichthyophis tricolor and Uraeotyphlus cf. narayani (Amphibia: Gymnophiona): Light and electron microscopic perspective
Authors: Smita Mathew , Oommen Oommen V. , George Jancy M. , Akbarsha M.A. 
Published: October 2003

AbstractThe caecilians have evolved a unique pattern of cystic spermatogenesis in which cysts representing different stages in spermatogenesis coexist in a testis lobule. We examined unsettled issues relating to the organization of the caecilian testis lobules, including the occurrence of a fatty matrix, the possibility of both peripheral and central Sertoli cells, the origin of Sertoli cells from follicular cells, and the disengagement of older Sertoli cells to become loose central Sertoli cells. We subjected the testis of Ichthyophis tricolor (Ichthyophiidae) and Uraeotyphlus cf. narayani (Uraeotyphliidae) from the Western Ghats of Kerala, India, to light and transmission electron microscopic studies. Irrespective of the functional state of the testis, whether active or regressed, Sertoli cells constitute a permanent feature of the lobules. The tall Sertoli cells adherent to the basal lamina with basally located pleomorphic nuclei extend deeper into the lobule to meet at the core. There they provide for association of germ cells at different stages of differentiation, an aspect that has earlier been misconceived as the fatty matrix. Germ cells up to the 4‐cell stage remain in the intercalating region of the Sertoli cells and they are located at the apices of the Sertoli cells from the 8‐cell stage onwards. The developing germ cells are intimately associated with the Sertoli cell adherent to the basal lamina until spermiation. There are ameboid cells in the core of the lobules that appear to interact with the germ cells at the face opposite to their attachment with the Sertoli cells. Adherence of the Sertoli cells to the basal lamina is a permanent feature of the caecilian testicular lobules. The ameboid cells in the core are neither Sertoli cells nor their degeneration products. J. Morphol. 258:317–326, 2003. © 2003 Wiley‐Liss, Inc.
Linking the microscopic view of chemistry to real‐life experiences: Intertextuality in a high‐school science classroom
Authors: Wu Hsin‐Kai 
Published: October 2003

AbstractChemistry learning involves establishing conceptual relationships among macroscopic, microscopic, and symbolic representations. Employing the notion of intertextuality to conceptualize these relationships, this study investigates how class members interactionally construct meanings of chemical representations by connecting them to real‐life experiences and how the teachers' content knowledge shapes their ways to coconstruct intertextual links with students. Multiple sources of data were collected over 7 weeks with a participation of 25 eleventh graders, an experienced teacher, and a student teacher. An examination of classroom discourse shows that the intertextual links between the microscopic view of chemistry and students' real‐life experiences could be initiated by students and instigated by the teachers. The teachers applied several discursive strategies to scaffold students building meaningful links based on their prior knowledge and experiences. Additionally, the experienced teacher with stronger content knowledge tended to present links in both dialogic and monologic discourses. Yet, the relatively limited content knowledge did not necessarily constrain the student teacher's interactions with students. The findings of this study provide a backdrop for further research to explore how chemistry is learned and taught in a class through the social constructivist lens. © 2003 Wiley Periodicals, Inc. Sci Ed 87:868–891, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/sce.10090