bluuebunny/crossref_metadata_2025_split huggingface dataset:
The p75NTR tumor suppressor induces caspase‐mediated apoptosis in bladder tumor cells
Authors: Tabassum Arshia , Khwaja Fatima , Djakiew Daniel 
Published: March 2003

Abstractp75NTR was identified as a tumor and metastasis suppressor that functions in part via induction of apoptosis in tumor cells. To examine p75NTR‐dependent apoptosis in tumor cells, we demonstrated that a dose‐dependent increase in p75NTR expression was associated with a concomitant increase in the mitochondrial proapoptotic effector proteins Bad, Bax and Bik and a decrease in the mitochondrial prosurvival effector proteins phospho‐Bad, Bcl‐2 and Bcl‐xL. Significantly, p75NTR‐dependent induction of cytochrome c release from the mitochondria occurred during CHX potentiation of apoptosis. Furthermore, p75NTR expression largely suppressed expression of IAP‐1 and induced cleavage of procaspase‐9 and procaspase‐7 but not of procaspases 2, 3, 6, 8 and 10. A specific peptide inhibitor of procaspase‐9 cleavage also inhibited cleavage of procaspase‐7, indicating that caspase‐7 is downstream of caspase‐9. As end points of apoptosis, we observed p75NTR‐dependent annexin V binding to the plasma membrane, an indicator of early apoptotic events, and Hoechst staining of DNA nuclear fragmentation, an indicator of late apoptotic events, whereas control tumor cells that lack expression of the p75NTR protein did not exhibit either of these apoptotic markers. Together, these results delineate the mitochondria‐mediated apoptotic pathway of the p75NTR tumor‐suppressor gene product. © 2003 Wiley‐Liss, Inc.
High delta‐like 1 expression in a subset of neuroblastoma cell lines corresponds to a differentiated chromaffin cell type
Authors: van Limpt Vera A.E. , Chan Alvin J. , van Sluis Peter G. , Caron Huib N. , van Noesel Carel J.M. , Versteeg Rogier 
Published: March 2003

AbstractThe childhood tumour neuroblastoma originates from neural crest‐derived progenitors of the sympathetic nervous system. By Serial Analysis of Gene Expression (SAGE), we previously identified the Drosophila Delta homologue Dlk1 as one of the genes most highly expressed in the neuroblastoma cell line SK‐N‐FI. The Delta‐Notch pathway controls many differentiation steps in Drosophila and man. We analysed expression of 21 genes of this pathway in 21 neuroblastoma cell lines. Dlk1 expression was very high in 5 cell lines, while another subset expressed Notch3. The imprinting of Dlk1 was faithfully preserved in neuroblastomas. The single paternal allele can therefore produce over 0.5% of all cellular mRNAs. Dlk1 maps to 14q32, a region that exhibited LOH in 31/170 (18%) tumours. The random parental origin of the deleted alleles excluded Dlk1 as target of the LOH. In addition, Dlk1 was not amplified, rearranged or mutated in neuroblastoma cell lines and tumours. We therefore analysed whether high Dlk1 expression marks a specific differentiation stage of the sympatho‐adrenal lineage. Many neuroblastomas arise in the adrenal medulla, which predominantly consists of chromaffin cells. Normal adrenal medulla exhibited equally high Dlk1 levels as the SK‐N‐FI cell line. Chromaffin cells in young children are marked by noradrenalin production, which is mediated by dopamine‐beta‐hydroxylase (DBH). DBH expression in the neuroblastoma cell lines almost perfectly corresponded to Dlk1 expression. Neuroblastoma cell lines with high Dlk1 expression are therefore arrested in a relatively late stage of chromaffin lineage differentiation, while Notch3 expression might correspond to earlier precursor stages or to an alternative developmental fate. © 2003 Wiley‐Liss, Inc.
Incidence of ocular melanoma in Australia from 1990 to 1998
Authors: Vajdic Claire M. , Kricker Anne , Giblin Michael , McKenzie John , Aitken Joanne , Giles Graham G. , Armstrong Bruce K. 
Published: March 2003

AbstractRoutinely collected incidence data have often lacked specific identification of ocular melanoma in the past and with increasing diagnosis and management of this disease by noninvasive techniques may now underestimate the true incidence. We attempted to accurately measure the incidence of ocular melanoma in Australia from 1990 to 1998 using 2 population‐based sources, cancer registries and ophthalmologists. We examined the distribution across the continent, by latitude and in subpopulations, and evaluated the extent of nonnotification to cancer registries. One‐half (51%) of the incident cases from 1996 to 1998 were diagnosed clinically and had no tissue diagnosis. An estimated 20% of melanomas, mainly those lacking a tissue diagnosis, were not notified to Australian cancer registries, but only 1.3% were not notified by ophthalmologists. Expert reviewers agreed that a high proportion (95%) of clinically diagnosed lesions were probable or possible melanomas. Incidence was significantly higher in men than in women, especially at older ages, relatively uniform across the Australian states with only weak evidence of a latitude gradient, and higher in rural than in urban areas. The incidence of ocular melanoma in people born in Southern Europe was half and in those born in Asia only 20% of the rate in people born in Australia and New Zealand. We concluded that it was possible to identify a high proportion of cases by surveying relevant sources additional to cancer registries and to be reasonably confident of the accuracy of the clinical diagnoses. The higher incidence in older men, who probably have higher sun exposure, than in older women and in residents of rural areas, where outdoor work is more prevalent, than in urban areas; the low incidence in dark‐eyed populations, who may have a lower sensitivity to or less transmission of solar radiation to the choroid; and the preferential location of ocular melanomas in ocular sites known to receive the highest exposure to solar radiation all support a role for solar radiation in the aetiology of ocular melanoma. The absence of a strong latitude gradient in incidence does not argue against such a role because exposure of the eye to solar UV is probably determined most by the horizon sky, where ambient solar UV is less affected by latitude. © 2003 Wiley‐Liss, Inc.
Biology of spermatozoa maturation: An overview with an introduction to this issue
Authors: Toshimori Kiyotaka 
Published: March 2003

AbstractMammalian spermatozoa undergo morphological, biochemical, and physiological modifications initially in the testis (testicular maturation) and later in the epididymis (epididymal maturation). These maturational changes are commensurate with the functional events that occur in developing germ cells and maturing spermatozoa. This special issue reviews the recent, relevant topics dealing with spermatozoa maturation and focuses on the events that occur in internal components such as the nucleus, the acrosome, the perinuclear theca, the fibrous sheath, and the cytoplasmic droplet as well as the plasma membrane. These structures/elements and the constituent proteins of which they are comprised undergo a variety of sequential modifications starting from their origination in developing germ cells up to epididymal maturation. Several steps of the maturation processes on the sperm plasma membrane are mediated by external enzymes and secretions derived from the epithelium lining of the genital tract. Degradation of some of the constituent proteins and the elimination of defective spermatozoa are controlled by the degradation/recycling system, the ubiquitin system. These maturational modifications are necessary for spermatozoa to become fertilization‐competent cells and to be stored safely in the male. Microsc. Res. Tech. 61:1–6, 2003. © 2003 Wiley‐Liss, Inc.
Contribution of epididymal secretory proteins for spermatozoa maturation
Authors: Dacheux Jean‐Louis , Gatti Jean Luc , Dacheux Françoise 
Published: March 2003

AbstractThe final stages of sperm differentiation occur outside the gonad and are not under the genomic control of germ cells. Only sequential interactions with the medium surrounding the sperm are believed to induce the final steps of spermatogenesis. The epididymis, a long tubule with very active secretory and reabsorption functions, is able to create sequential changes in the composition of luminal fluid throughout its length. The chronologies of the changes, which occur on/in the sperm with those in their surrounding environment, are described. Correlations between the highly regionalized epididymal activities and sperm characteristics linked to their survival and fertility potential are presented in this review. Microsc. Res. Tech. 61:7–17, 2003. © 2003 Wiley‐Liss, Inc.
Glycan modifying enzymes in luminal fluid of rat epididymis: Are they involved in altering sperm surface glycoproteins during maturation?
Authors: Tulsiani Daulat R.P. 
Published: March 2003

AbstractTesticular spermatozoa undergo morphological and biochemical alterations, collectively termed epididymal maturation, in the intraluminal environment of epididymis. As a result of these modifications, the spermatozoon becomes a motile and functionally competent cell capable of undergoing capacitation and binding to the zona pellucida, the extracellular coat that surrounds the mammalian oocyte. Although details of all the changes are not fully known, several studies provide evidence suggesting that sperm plasma membrane undergoes extensive biochemical changes, including organization and modification of surface glycoproteins as spermatozoa transit from the proximal to the distal epididymis. In this article, I have attempted to summarize results with two sets of glycoprotein (glycan)‐modifying enzymes, namely, glycohydrolases (hydrolytic enzymes) and glycosyltransferases (synthetic enzymes) present in the epididymal luminal fluid (LF). The in vitro experimental approaches described in this report demonstrate that: 1) a PNA‐positive glycoprotein(s) (containing O‐linked glycan) of 135–150 kDa subunit molecular mass which is present on the surface of caput (but not the cauda) spermatozoa can be degalactosylated by the enzymatic digestion with LF β‐D‐galactosidase; and 2) an N‐linked glycan chain(s) which is present on a sperm surface glycoprotein (apparent subunit molecular mass of 86 kDa) can be fucosylated in vitro when distal caput sperm (or sperm plasma membrane‐rich fractions) are incubated in the presence of a nucleotide sugar (GDP[14C]fucose). Combined, these results strongly suggest a role for the glycan‐modifying enzymes in degalactosylation and fucosylation of sperm surface glycoproteins during epididymal transit. Microsc. Res. Tech. 61:18–27, 2003. © 2003 Wiley‐Liss, Inc.
Acquisition of volume regulatory response of sperm upon maturation in the epididymis and the role of the cytoplasmic droplet
Authors: Cooper Trevor G. , Yeung Ching‐Hei 
Published: March 2003

AbstractIn certain cases of infertility in domestic species, and in the homozygous c‐ros tyrosine kinase knockout mouse, males are infertile as a result of unopposed sperm swelling. This induces flagellar angulation, preventing their normal migration in the female tract. Angulation always occurs at the site of the cytoplasmic droplet located in mature sperm at the annulus (midpiece – principal piece junction). This article reviews the literature on the fate of the sperm's cytoplasmic droplet and suggests a role for it in volume regulation. A hypothesis is presented that during epididymal transit sperm acquire osmolytes accumulated by the epididymal epithelium. This is possibly driven by a mechanism of regulatory volume increase invoked by the hypertonicity of epididymal luminal fluid. These osmolytes are subsequently used for regulatory volume decrease after ejaculation into the relatively hypotonic female tract. Study of the mechanisms of sperm volume regulation may highlight new contraceptive leads. Microsc. Res. Tech. 61:28–38, 2003. © 2003 Wiley‐Liss, Inc.
Structural modification of the hamster sperm acrosome during posttesticular development in the epididymis
Authors: Olson Gary E. , Winfrey Virginia P. , Nagdas Subir K. 
Published: March 2003

AbstractThe acrosome of the mature spermatozoon functions as a regulated secretory vesicle which performs several critical functions in mammalian fertilization. Acrosome assembly occurs throughout spermiogenesis and continues during posttesticular sperm maturation in the epididymis, resulting in a structurally polarized membrane‐bounded organelle that contains an assortment of hydrolases and a stable infrastructure termed the acrosomal matrix. The role of stable acrosomal matrix assemblies in acrosomal biogenesis and function are poorly understood. This article presents ultrastructural, immunocytochemical, and biochemical data on the remodeling of the hamster acrosomal matrix during spermiogenesis and posttesticular sperm maturation in the epididymis. Specific posttranslational modifications of the major acrosomal matrix protein are evident in late, step 16, spermatids and matrix protein processing continues within specific acrosomal subdomains of caput epididymal spermatozoa. At the completion of sperm maturation, the acrosomal matrix consists of two structurally distinct domains which are adherent to the outer acrosomal membrane and exhibit a localized distribution pattern. Coincident with acrosomal matrix differentiation, a paracrystalline cytoskeletal complex is assembled onto the outer acrosomal membrane of epididymal spermatozoa. This cytoskeletal network appears to establish transmembrane structural interactions with the acrosomal matrix and may maintain attachment of the acrosomal cap to the sperm head during the early steps of the acrosome reaction. Microsc. Res. Tech. 61:46–55, 2003. © 2003 Wiley‐Liss, Inc.
Perinuclear theca during spermatozoa maturation leading to fertilization
Authors: Müjica Adela , Navarro‐García Fernando , Hernández‐González Enrique O. , de Lourdes Juárez‐Mosqueda María 
Published: March 2003

AbstractMammalian spermatozoa acquire the capacity to fertilize the ovum and display motility during their passage through the epididymis. At the same time, they undergo changes in metabolic patterns, enzymatic activities, ability to bind to zona pellucida surface, and electrophoretic properties and, furthermore, stabilization of some sperm structures by the establishment of disulphide linkages takes place in several sperm structures. The cytoplasmic perinuclear theca (PT) is a unique extranuclear cytoskeletal element that surrounds the nucleus, which is proposed to be a structural scaffold to the sperm nucleus. The purpose of this review is to describe PT changes related to epididymal sperm maturation. We will focus mainly on the protein components of the PT of eutherian mammalian spermatozoa and on quantitative protein changes during sperm maturation. The protein constituents of the PT have not been completely defined and most of them are different from the cytoskeletal proteins of somatic cells. However, they are proteins with cytoskeletal features. The morphologic changes reported for PT and the proposed functions of PT are discussed. Microsc. Res. Tech. 61:76–87, 2003. © 2003 Wiley‐Liss, Inc.
Ubiquitin‐dependent proteolysis in mammalian spermatogenesis, fertilization, and sperm quality control: Killing three birds with one stone
Authors: Sutovsky Peter 
Published: March 2003

AbstractUbiquitin and ubiquitin‐like proteins control the degradation of substrates as diverse as cyclins, viral envelope proteins, plasma membrane receptors, and mRNAs. The ubiquitinated substrates are targeted towards the lysosomal or proteasomal degradation sites. The number and position of ubiquitin molecules bound to substrates' lysine residues and the number and position of ubiquitin molecules in polyubiquitin chains determine the astonishing substrate specificity of ubiquitin‐mediated proteolysis. Ubiquitin is likely to be expressed in mammalian gametes and embryos at any given developmental step, but the information on ubiquitin dependence of gametogenesis and fertilization is sketchy. Ubiquitin ligases E1, E2, E3, and UBC4 are active in the testis. Ubiquitin and proteasomal subunits can be detected in the human sperm centrosome that undergoes dramatic reduction during spermatid elongation. Spermatid histones are ubiquitinated as they are being transiently replaced by transitional proteins and permanently by protamines. Ubiquitin tagging of the sperm mitochondrial membranes may serve as a death sentence for paternal mitochondria at fertilization, thus promoting the maternal inheritance of mitochondrial DNA (mtDNA) in mammals. The defective spermatozoa become surface‐ubiquitinated during sperm descent down the epididymis. Finally, new evidence suggests the involvement of ubiquitin‐proteasome pathway in the zona penetration by the acrosome‐reacted spermatozoon. Such differential patterns of ubiquitination in the testis and epididymis, and inside the egg, may be necessary for reproductive success in humans and animals. Deciphering and eventually manipulating the ubiquitin‐dependent proteolysis in the reproductive system could allow us to redirect the mode of mtDNA inheritance after cloning and ooplasmic transplantation, provide germ line therapy in some cases of male infertility, develop new contraceptives, manage polyspermia during in vitro fertilization, and establish objective markers for infertility diagnostics, semen evaluation, and prediction of future fertility. Microsc. Res. Tech. 61:88–102, 2003. © 2003 Wiley‐Liss, Inc.
Fibrous sheath of mammalian spermatozoa
Authors: Eddy Edward M. , Toshimori Kiyotaka , O'Brien Deborah A. 
Published: March 2003

AbstractThe fibrous sheath is a unique cytoskeletal structure surrounding the axoneme and outer dense fibers and defines the extent of the principal piece region of the sperm flagellum. It consists of two longitudinal columns connected by closely arrayed semicircular ribs that assemble from distal to proximal throughout spermiogenesis. The fibrous sheath is believed to influence the degree of flexibility, plane of flagellar motion, and the shape of the flagellar beat. Nearly half of the protein in fibrous sheaths isolated from mouse sperm is AKAP4. This protein and two others, AKAP3 and TAKAP‐80, have anchoring sites for cAMP‐dependent protein kinase. AKAP3 also anchors ropporin, a spermatogenic cell‐specific protein that is linked through rhophilin to the small GTPase Rho. Other proteins associated with the fibrous sheath include two enzymes in the glycolytic pathway. Glyceraldehyde 3‐phosphate dehydrogenase‐s (GAPDS) is the product of a gene expressed only in spermatogenic cells, while hexokinase type 1‐s (HK1‐S) is derived from alternative transcripts present only in spermatogenic cells. Most of the other glycolytic enzymes in sperm have unique structural or functional properties. The fibrous sheath also contains a spermatogenic cell‐specific member of the μ‐class glutathione S‐transferase family (GSTM5) and an intermediate filament‐like protein (FS39). These and other observations indicate that the fibrous sheath functions as a scaffold for proteins in signaling pathways that might be involved in regulating sperm maturation, motility, capacitation, hyperactivation, and/or acrosome reaction and for enzymes in the glycolytic pathway that provide energy for the hyperactivated motility of sperm that allows them to penetrate the zona pellucida. Microsc. Res. Tech. 61:103–115, 2003. Published 2003 Wiley‐Liss, Inc.
Ribavirin reduces clinical signs and pathological changes of experimental autoimmune encephalomyelitis in Dark Agouti rats
Authors: Milicevic Irena , Pekovic Sanja , Subasic Sanja , Mostarica‐Stojkovic Marija , Stosic‐Grujicic Stanislava , Medic‐Mijacevic Ljubica , Pejanovic Vjera , Rakic Ljubisav , Stojiljkovic Mirjana 
Published: March 2003

AbstractThe effect of ribavirin on development of experimental autoimmune encephalomyelitis (EAE) was investigated. The disease was induced in genetically susceptible Dark Agouti rats with syngeneic spinal cord homogenate in complete Freund's adjuvant (SCH‐CFA). Depending on the amount of mycobacteria in CFA, the animals developed either moderate or severe EAE. Ribavirin (1‐β‐D‐ribofuranosyl‐1,2,4‐triazole‐3‐carboxamide) was applied i.p. at a daily dosage of 30 mg/kg in two treatment protocols: from the start of immunization (preventive treatment) or from the onset of the first EAE signs after the induction (therapeutic treatment). Signs of EAE began between 7 and 9 days after induction and peaked at days 11–13. In moderate EAE (mean maximal severity score 3.33 ± 0.21), the recovery was completed by days 23–26, whereas, in severe EAE (mean maximal severity score 4.5 ± 0.23), obvious recovery was not detected. Preventive ribavirin treatment significantly decreased clinical signs after both moderate (score 1.75 ± 0.25, P < 0.05) and severe (score 3.62 ± 0.31, P < 0.015) immunization. Also, disease manifestations were reduced by therapeutic treatment of ribavirin (mean maximal severity score 2.5 ± 0.2 vs. 3.33 ± 0.21 in controls, P < 0.005) but less so in comparison with preventive treatment. Analysis of the effects of ribavirin on histopathologic changes in the spinal cord tissue revealed a reduction of mononuclear cell infiltrates, composed of T cells and macrophages/microglia, and the absence of demyelination, which were pronounced in control EAE animals. Beneficial effects of preventive and therapeutic treatment with ribavirin on development of EAE suggest this nucleoside analogue as a useful candidate for therapy in multiple sclerosis. © 2003 Wiley‐Liss, Inc.
Glutamate regulates caveolin expression in rat hippocampal neurons
Authors: Bu Jing , Bruckner Shane R. , Sengoku Tomoko , Geddes James W. , Estus Steven 
Published: March 2003

AbstractCaveolae are cholesterol‐rich, membrane microdomains that appear critical to signaling between extracellular and intracellular macromolecules as well as cholesterol homeostasis. Caveolae formation is modulated by caveolin, a protein family that is the proteinaceous hallmark of caveolae. Very little is known regarding the events that modulate caveolin expression and regulation in neurons. To detect caveolin expression in neurons, primary rat hippocampal neurons were harvested at embryonic day 18, maintained for 7 days in vitro, and then analyzed for caveolin immunofluorescence. Caveolin‐1 immunoreactivity was detected in cells that were identified as neurons by morphology and concurrent microtubule‐associated protein (MAP2) staining. Changes in caveolin‐1 expression were evaluated by reverse transcriptase‐polymerase chain reaction (RT‐PCR) analyses of RNA isolated from hippocampal neurons treated with glutamate receptor agonists. Glutamate induced a concentration‐dependent increase in caveolin‐1 mRNA. The largest increases in caveolin‐1 mRNA were detected after 6 hours of treatment. Kainate and AMPA both mimicked glutamate effects on caveolin‐1 mRNA expression. Western blot analyses revealed that caveolin was induced at the protein level as well. Taken together, these data suggest that glutamate can regulate caveolin expression through kainate and AMPA ionotropic glutamate receptors. © 2003 Wiley‐Liss, Inc.