bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD4+CD25+ regulatory T cells in patients with gastrointestinal malignancies
Authors: Sasada Tetsuro , Kimura Motohide , Yoshida Yuka , Kanai Michiyuki , Takabayashi Arimichi 
Published: August 2003

AbstractBACKGROUNDActive suppression by CD4+CD25+ regulatory T cells plays an important role in the down‐regulation of the response of T cells to foreign and self antigens. Experimental tumor models in mice revealed that regulatory T cells inhibit antitumor immune responses. The purpose of the current study was to demonstrate the possible involvement of CD4+CD25+ regulatory T cells in immune system impairment in patients with gastrointestinal malignancies.METHODSThe phenotypes of lymphocytes, particularly those of CD4+CD25+ T cells, were analyzed in peripheral blood in 149 patients with gastrointestinal malignancies and in ascites in 7 patients with peritoneal dissemination. In addition, cytokine production after in vitro stimulation was examined in CD4+CD25+ and CD4+CD25− T cells isolated from patients with malignant disease.RESULTSCompared with healthy volunteers, patients with gastrointestinal malignancies had a higher proportion of CD4+CD25+ T cells in peripheral blood, due to the presence of a drastically smaller number of CD4+CD25− T cells. Among patients with gastric carcinoma, those with higher percentages of CD4+CD25+ T cells had a poorer prognosis than did those with lower percentages. CD4+CD25+ T cells also were present in greater proportions in ascites from patients who had advanced‐stage disease with peritoneal dissemination. Isolated CD4+CD25+ T cells from patients with malignant disease produced interleukin (IL)‐4 and IL‐10 but not IL‐2 or interferon‐γ; these cells also inhibited cytokine production by CD4+CD25− T cells after in vitro stimulation.CONCLUSIONSThe relative increase in CD4+CD25+ regulatory T cells may be related to immunosuppression and tumor progression in patients with gastrointestinal malignancies. This finding suggests that the use of immunomodulatory therapy to treat patients with gastrointestinal malignancies may be an effective strategy. Cancer 2003;98:1089–99. © 2003 American Cancer Society.DOI 10.1002/cncr.11618
Expression of translation initiation factor eIF‐2α is increased in benign and malignant melanocytic and colonic epithelial neoplasms
Authors: Rosenwald Igor B. , Wang Songtao , Savas Lou , Woda Bruce , Pullman James 
Published: August 2003

AbstractBACKGROUNDStimulation of resting cells by growth factors leads to an increase in the rate of protein synthesis, which is necessary for cell growth and division. Translation initiation factor eIF‐2α is one of the key translation factors mediating the effects of growth factors on protein synthesis. In normal cells, expression of eIF‐2α is increased transiently, but its levels are elevated constitutively in oncogene‐transformed cells. Overexpression of constitutively active eIF‐2α in rodent cells makes them tumorigenic. In this article, the authors report their findings on the increased expression of eIF‐2α in human benign and malignant neoplasms originating from melanocytes and colonic epithelium.METHODSImmunohistochemistry was used to analyze the expression of eIF‐2α, eIF‐4E, and cyclin D1 in melanocytic nevi and melanomas and the expression of eIF‐2α in colonic adenomas and carcinomas.RESULTSThe authors found that the expression of eIF‐2α was increased markedly in both benign and malignant neoplasms of melanocytes and colonic epithelium.CONCLUSIONSIncreased expression of eIF‐2α took place in both benign and malignant neoplasms of melanocytes and colonic epithelium. These findings suggest that elevated expression of this translation initiation factor may contribute to tumor initiation and progression but that it is not sufficient for establishing a malignant phenotype in the tumors analyzed in this study. Cancer 2003;98:1080–8. © 2003 American Cancer Society.DOI 10.1002/cncr.11619
Results of triple therapy with interferon‐alpha, cytarabine, and homoharringtonine, and the impact of adding imatinib to the treatment sequence in patients with Philadelphia chromosome–positive chronic myelogenous leukemia in early chronic phase
Authors: O'Brien Susan , Giles Francis , Talpaz Moshe , Cortes Jorge , Rios Mary Beth , Shan Jianqin , Thomas Deborah , Andreeff Michael , Kornblau Steven , Faderl Stefan , Garcia‐Manero Guillermo , White Kevin , Mallard Susie , Freireich Emil , Kantarjian Hagop M. 
Published: August 2003

AbstractBACKGROUNDBefore the discovery of imatinib mesylate, a Bcr‐Abl selective tyrosine kinase inhibitor, three agents, interferon‐alpha (IFN‐α), cytarabine (ara‐C), and homoharringtonine (HHT), had demonstrated activity against Philadelphia chromosome (Ph)‐positive chronic myelogenous leukemia (CML) as single agents and in couplet combinations. The goals of the current study were to evaluate the efficacy of the triple combination regimen with IFN‐α, ara‐C, and HHT in newly diagnosed Ph‐positive CML and to assess the impact of the added sequential therapy with imatinib on overall prognosis.METHODSNinety patients with Ph‐positive CML in early chronic phase received the triple regimen. Therapy consisted of 5 million units (MU)/m2 IFN‐α subcutaneously (s.c. daily, ara‐C 10 mg s.c. daily, and HHT 2.5 mg/m2 by continuous infusion over 24 hours daily × 5 every month. After a median duration of 16.5 months of therapy, 78 patients had their therapy changed to 400 mg orally administered imatinib daily.RESULTSWith the triple regimen, 85 patients (94%) achieved complete hematologic response and 67 patients (74%) had a cytogenetic response (Ph suppression to ≤ 90%) which was complete (Ph 0%) in 20 patients (22%) and major in 42 patients (46%). Myelosuppression was significant, resulting in considerable reductions in the dose schedules. After 12 months of therapy, the median IFN‐α dose was 1.6 MU/m2 daily, the median ara‐C dose was 1.85 mg daily, and the median number of HHT days was 2 every month. Only three patients developed blastic phase while receiving the triple regimen. With the change to imatinib therapy, currently 57 patients (63%) are in complete cytogenetic response and 69 patients (76%) in major cytogenetic response. With a median follow‐up time of 46 months for the total study group, the estimated 5‐year survival rate was 88%, and only 8 patients (9%) to date have developed blastic phase.CONCLUSIONSThe sequence of IFN‐α, ara‐C, and HHT followed by imatinib (imposed by the discovery of the latter drug) resulted in an estimated 5‐year survival rate of 88%. This finding suggests that imatinib combination regimens may improve the prognosis in CML. Cancer 2003;98:888–93. © 2003 American Cancer Society.DOI 10.1002/cncr.11620
Primary central nervous system lymphoma: Phase I evaluation of infusional bromodeoxyuridine with whole brain accelerated fractionation radiation therapy after chemotherapy
Authors: Dabaja Bouthaina S. , McLaughlin Peter , Ha Chul S. , Pro Barbara , Meyers Christina A. , Seabrooke Lee F. , Wilder Richard B. , Kyritsis Athanassios P. , Preti H. Alejandro , Yung W. K. Alfred , Levin Victor , Cabanillas Fernando , Cox James D. 
Published: August 2003

AbstractBACKGROUNDThe current study was performed to determine the maximum tolerated dose (MTD), toxicity, and outcome of infusional 5 bromo‐2'‐deoxyuridine (bromodeoxyuridine; BUdR) given with accelerated fractionation whole brain radiation therapy (WBRT) after chemotherapy for the treatment of primary central nervous system lymphoma (PCNSL).METHODSTwelve patients with untreated and histologically confirmed PCNSL were entered on the study between 1994 and 1996. Chemotherapy was comprised of one course of IDHAP plus high‐dose methotrexate (HD‐MTX). IDHAP is comprised of idarubicin at a dose of 1.5 mg/m2/day × 4 days intravenously by continuous infusion (i.v. CI), dexamethasone at a dose of 40 mg i.v. on Days 1–5, cytosine arabinoside at a dose of 2000 mg/ m2 i.v. on Day 5 after cisplatin, and cisplatin at a dose of 25 mg/m2/day × 4 days i.v. CI. HD‐MTX was given at a dose of 3.5 g/m2 i.v. between Day 10 and Day 14 after IDHAP. BUdR was given as an i.v. CI over 48 hours, 2–3 days prior to WBRT and then weekly during WBRT. Dose escalation started at 1.5 g/m2/day for Cohort 1 with subsequent increments of 0.3 g/m2/day. The WBRT dose was 45 grays (Gy) at a dose of 1.5 Gy twice a day, 5 days per week. Neurocognitive testing was performed before, during, and after treatment.RESULTSNine of 12 patients entered on the study received BUdR. One of 3 patients in Cohort 1 developed leukoencephalopathy (LEP), a dose‐limiting toxicity (DLT), within 2 months of the completion of therapy. Therefore, the next cohort received the same dose level. Because no toxicity was observed in Cohort 2, the third cohort received a BUdR dose of 1.8 g /m2/day. Shortly after completing enrollment in Cohort 3, 3 more patients developed LEP, including 2 from Cohort 1 who had received a dose of 1.5 g/m2/day. Thus, DLT occurred at a dose of 1.5 g/m2/day, the starting level in the current study. As a result, the trial was stopped. Eight of 12 patients achieved a complete response, 3 achieved a partial response, and 1 patient died before response assessment.CONCLUSIONSHyperfractionated WBRT with concurrent BUdR after chemotherapy was found to result in modest disease control but has unacceptable neurotoxicity. Cancer 2003;98:1021–8. © 2003 American Cancer Society.DOI 10.1002/cncr.11627
Time course of early motor and neuropathological anomalies in a knock‐in mouse model of Huntington's disease with 140 CAG repeats
Authors: Menalled Liliana B. , Sison Jessica D. , Dragatsis Ioannis , Zeitlin Scott , Chesselet Marie‐Françoise 
Published: August 2003

AbstractHuntington's disease (HD) is caused by an abnormal expansion of CAG repeats in the gene encoding huntingtin. The development of therapies for HD requires preclinical testing of drugs in animal models that reproduce the dysfunction and regionally specific pathology observed in HD. We have developed a new knock‐in mouse model of HD with a chimeric mouse/human exon 1 containing 140 CAG repeats inserted in the murine huntingtin gene. These mice displayed an increased locomotor activity and rearing at 1 month of age, followed by hypoactivity at 4 months and gait anomalies at 1 year. Behavioral symptoms preceded neuropathological anomalies, which became intense and widespread only at 4 months of age. These consisted of nuclear staining for huntingtin and huntingtin‐containing nuclear and neuropil aggregates that first appeared in the striatum, nucleus accumbens, and olfactory tubercle. Interestingly, regions with early pathology all receive dense dopaminergic inputs, supporting accumulating evidence for a role of dopamine in HD pathology. Nuclear staining and aggregates predominated in striatum and layer II/III and deep layer V of the cerebral cortex, whereas neuropil aggregates were found in the globus pallidus and layer IV/superficial layer V of the cerebral cortex. The olfactory system displayed early and marked aggregate accumulation, which may be relevant to the early deficit in odor discrimination observed in patients with HD. Because of their early behavioral anomalies and regionally specific pathology, these mice provide a powerful tool with which to evaluate the effectiveness of new therapies and to study the mechanisms involved in the neuropathology of HD. J. Comp. Neurol. 465:11–26, 2003. © 2003 Wiley‐Liss, Inc.
Complementary distribution of vesicular glutamate transporters 1 and 2 in the nucleus accumbens of rat: Relationship to calretinin‐containing extrinsic innervation and calbindin‐immunoreactive neurons
Authors: Härtig Wolfgang , Riedel Anett , Grosche Jens , Edwards Robert H. , Fremeau Robert T. , Harkany Tibor , Brauer Kurt , Arendt Thomas 
Published: August 2003

AbstractThe caudomedial shell of the rat nucleus accumbens exhibits inhomogeneous distribution patterns of the vesicular glutamate transporters 1 (VGLUT1) and 2 (VGLUT2). This paper focuses on the question of whether patterns of VGLUT1 and VGLUT2 correspond to cytoarchitectonically and cytochemically defined subterritories of the caudomedial shell region. VGLUT2 was shown to be coexpressed with calretinin in the dense axonal plexus known to emanate from the paraventricular thalamic nucleus. In regions termed corridors, which are spared by this paraventricular thalamic innervation, axonal terminals were found to be clustered and VGLUT1‐immunoreactive. It is assumed that these fibers originate in the prelimbic cortex and/or in the parvicellular basal amygdaloid nucleus known to project to accumbal shell components. Our findings confirm the existence of two well‐separated neuronal circuits in the caudomedial shell that are dominated by two different excitatory input systems originating from either thalamic, cortical, or cortex‐like amygdaloid sources. The large lateral corridors—which resemble the accumbal core not only in respect to their VGLUT1 immunolabeling but also concerning their content of calbindin‐positive cells—may represent a component of the anatomically weakly defined accumbal shore region. J. Comp. Neurol. 465:1–10, 2003. © 2003 Wiley‐Liss, Inc.
Distribution of the vanilloid receptor (VR1) in the gastrointestinal tract
Authors: Ward Sean M. , Bayguinov Julia , Won Kyung‐Jong , Grundy David , Berthoud Hans R. 
Published: August 2003

AbstractThe gastrointestinal (GI) tract responds to a variety of stimuli through local and centrally mediated pathways. Changes in the intestinal microenvironment are sensed by vagal, spinal, and intrinsic primary afferent fibers. Sensory nerve endings located close to the lumen of the GI tract respond to pH, chemical composition of lumenal contents, or distortion of the mucosa. Afferents within the muscle layers are thought to be tension sensitive, whereas those located within the myenteric plexus are also thought to respond to changes in chemical composition and humoral substances. Subpopulations of these afferent fibers are activated by capsaicin. However, the exact location of these nerves is currently not known. The vanilloid receptor (VR1) is a nonselective cation channel that is activated by capsaicin, acid, and temperature. Antibodies to VR1 make it possible to determine the location of these afferents, their morphology, and their relationships with enteric nerves and other cell types in the GI tract. VR1‐like immunoreactivity was observed on nerves within myenteric ganglia and interganglionic fiber tracts throughout the GI tract. VR1 nerves were also observed within the muscle layers and had an irregular profile, with varicose‐like swellings along their lengths. Blood vessels within the GI wall had VR1‐immunoreactive nerve fibers associated with them. VR1‐like nerves and other immunopositive cells were also observed within the mucosa. In summary, VR1‐like immunoreactivity was found in several locations within the GI tract and may provide sensory integration of chemical, physical, or inflammatory stimuli. VR1‐like fibers appear to be predominantly spinal in origin, but a few vagal VR1‐like fibers exist in the stomach. J. Comp. Neurol. 465:121–135, 2003. © 2003 Wiley‐Liss, Inc.
Evidence for estrogenic regulation of gonadotropin‐releasing hormone neurons by glutamatergic neurons in the ewe brain: An immunohistochemical study using an antibody against vesicular glutamate transporter‐2
Authors: Pompolo Sueli , Pereira Alda , Scott Christopher James , Fujiyma Fumino , Clarke Iain James 
Published: August 2003

AbstractGonadotropin‐releasing hormone (GnRH) secretion is controlled by various factors, including the excitatory neurotransmitter glutamate. Estrogen (E) regulates GnRH secretion by means of E‐responsive cells in the brain that relay the feedback effects to the preoptic area (POA). We used an antibody to vesicular glutamate transporter 2 (VGluT2) to label glutamatergic neurons in the areas of the ewe brain that control GnRH secretion. VGluT2‐immunoreactive cells were observed in the arcuate nucleus (ARC)/ventromedial hypothalamic nucleus (VMH) complex, POA, bed nucleus of stria terminalis (BnST), and A1 and A2 cell groups in the brainstem. In three ewes, E receptor‐α was detected in 52–61% of glutamatergic neurons in ARC/VMH, 37–52% of neurons in the POA, and 37–58% of neurons in the BnST. E injection (i.m. or i.v.) increased the percentage of glutamatergic cells that expressed Fos protein in the ARC (P< 0.01 andP< 0.001, respectively). In six ewes, injection of the retrograde tracer Fluoro‐Gold into the POA labeled cells in the ARC and 6–29% of these were also VGluT2‐immunoreactive. Double‐labeling of varicosities in the POA showed colocalization of VGluT2 in 12.5 ± 3% of dopamine β‐hydroxylase–immunoreactive terminals, indicating that a subset of glutamatergic inputs could arise from brainstem noradrenergic neurons cells. In the POA, 60% of GnRH neurons had close appositions that were VGluT2‐immunoreactive. We conclude that E‐responsive glutamatergic neurons arising from the brainstem, the BnST, and ARC/VMH provide input to the POA and may be involved in the regulation of GnRH secretion. J. Comp. Neurol. 465:136–144, 2003. © 2003 Wiley‐Liss, Inc.
ATBF1‐A protein, but not ATBF1‐B, is preferentially expressed in developing rat brain
Authors: Ishii Yoko , Kawaguchi Makoto , Takagawa Kiyoshi , Oya Takeshi , Nogami Shigeharu , Tamura Amane , Miura Yutaka , Ido Akio , Sakata Nobuo , Hashimoto‐Tamaoki Tomoko , Kimura Tomoatsu , Saito Takayoshi , Tamaoki Taiki , Sasahara Masakiyo 
Published: August 2003

AbstractThe ATBF1 gene encodes transcription factors containing four homeodomains and multiple zinc finger motifs. However, the gene products have yet to be identified and the role remains unknown in vivo. In this study, we raised an antiserum for ATBF1 and found high levels of expression of ATBF1 in developing rat brain. Western and Northern blot analyses detected a 400 kDa protein and 12.5 kb mRNA in developing rat brain, respectively; both corresponding to ATBF1‐A but not the B isoform. The protein was highly expressed in the midbrain and diencephalon and mRNA was highly expressed in the brainstem, mostly in embryo and neonatal brain. Immunohistochemistry identified postmitotic neurons in the brainstem as the major site of ATBF1 expression, and the expression levels varied depending on age of and location in the brain. Expression was transient and weak in the precursor cells at early neurogenesis. ATBF1 decreased postnatally, but remained in mature neurons, including those expressing DOPA decarboxylase (DDC). High levels of ATBF1 were expressed in precursor cells in accordance with neurogenesis and were continued to the mature neurons in specific areas such as the inferior colliculus. Expression was not significant from precursor cells to mature neurons in the cerebral cortex and hippocampus. ATBF1 and its Drosophila homolog, Zfh‐2, are known to regulate cell differentiation and proliferation via the interaction with either of the basic helix‐loop‐helix transcription factors, c‐myb, or the DDC gene. Together with these reported functions the expression features detected here suggest that ATBF1 may participate in the regulation of neuronal cell maturation or region‐specific central nervous system differentiation. J. Comp. Neurol. 465:57–71, 2003. © 2003 Wiley‐Liss, Inc.
Glomerular territories in the olfactory bulb from the larval stage of the sea lamprey Petromyzon marinus
Authors: Frontini Andrea , Zaidi Aliya U. , Hua Hong , Wolak Tomasz P. , Greer Charles A. , Kafitz Karl W. , Li Weiming , Zielinski Barbara S. 
Published: August 2003

AbstractThe goal of this study was to investigate the spatial organization of olfactory glomeruli and of substances relevant to olfactory sensory neuron activity in the developing agnathan, the sea lamprey Petromyzon marinus. A 45‐kD protein immunoreactive to Golf, a cAMP‐dependent olfactory G protein, was present in the ciliary fraction of sea lamprey olfactory epithelium and in olfactory sensory neurons of larval and adult sea lampreys. This result implies that Golf expression was present during early vertebrate evolution or evolved in parallel in gnathostome and agnathostome vertebrates. Serial sectioning of the olfactory bulb revealed a consistent pattern of olfactory glomeruli stained by GS1B4 lectin and by anterograde labeling with fluorescent dextran. These glomerular territories included the dorsal cluster, dorsal ring, anterior plexus, lateral chain, medial glomeruli, ventral ring, and ventral cluster. The dorsal, anterior, lateral, and ventral glomeruli contained olfactory sensory axon terminals that were Golf‐immunoreactive. However, a specific subset, the medial glomeruli, did not display this immunoreactivity. Olfactory glomeruli in the dorsal hemisphere of the olfactory bulb, the dorsal cluster, dorsal ring, anterior plexus, lateral chain, and medial glomeruli, were seen adjacent to 5HT‐immunoreactive fibers. However, glomeruli in the ventral hemisphere, the ventral ring, and ventral cluster did not display this association. The presence of specific glomerular territories and discrete glomerular subsets with substances relevant to olfactory sensory neuron activity suggest a spatial organization of information flow in the lamprey olfactory pathway. J. Comp. Neurol. 465:27–37, 2003. © 2003 Wiley‐Liss, Inc.
Somatosensory organization and behavior in naked mole‐rats: II. Peripheral structures, innervation, and selective lack of neuropeptides associated with thermoregulation and pain
Authors: Park Thomas J. , Comer Christopher , Carol Andrew , Lu Ying , Hong H.‐S. , Rice Frank L. 
Published: August 2003

AbstractAfrican naked mole‐rats are subterranean rodents that have a robust orienting response to stimulation of unique vibrissa‐like body hairs that are widely spaced over an otherwise hairless skin. To determine whether these large body hairs have a specialized organization similar to facial vibrissae, the structure and innervation of facial vibrissa follicles, body hair follicles, and intervening skin in naked mole‐rats was compared with that in rats and a furred African mole‐rat species (the common mole‐rat). Immunofluorescence and lectin‐binding analyses revealed that the body hair follicles in naked mole‐rats were exceptionally large and well innervated, similar to guard hairs of furred species. However, these body vibrissae lacked the anatomic specializations and unique types of innervation affiliated with follicle sinus complexes of facial vibrissae. In contrast to the furred species, naked mole‐rats had a paucity of Aβ‐fiber Merkel endings at all peripheral locations. Naked mole‐rats also were completely lacking in cutaneous C‐fibers immunoreactive for substance P and calcitonin gene‐related peptide. In contrast, the hairless skin of the naked mole‐rats had an exceptional abundance of presumptive Aδ‐fibers. The unusual features of the cutaneous innervation in naked mole‐rats are presumably adaptations to their subterranean environment and that they are the only known poikilothermic mammal. The features of this mammalian model system provide unique opportunities to discriminate mechanisms related to tactile spatial orientation, vascular regulation, and nociception. J. Comp. Neurol. 465:104–120, 2003. © 2003 Wiley‐Liss, Inc.