bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II study of neoadjuvant biochemotherapy for stage III melanoma
Authors: Gibbs Peter , Anderson Clay , Pearlman Nathan , LaClaire Stacy , Becker Maude , Gatlin Kristi , O'Driscoll Martin , Stephens Janet , Gonzalez Rene 
Published: August 2002

AbstractBACKGROUNDPhase II studies of biochemotherapy (combining interleukin‐2, interferon‐α, and multiagent chemotherapy) have reported high response rates and a significant number of durable complete responses in patients with metastatic melanoma.METHODSA pilot Phase II study was performed to explore the safety and activity of neoadjuvant biochemotherapy in patients with Stage III melanoma. Forty‐eight patients were enrolled between April 1996 and May 1999. The median age of the patients was 46 years (range, 19–70 years). Two cycles of biochemotherapy were administered prior to and after complete lymph node dissection. Each cycle was comprised of cisplatin, 20 mg/m2 intravenously (i.v.), on Days 1–4; vinblastine, 1.6 mg/m2 i.v., on Days 1–4; dacarbazine, 800 mg/m2 i.v., on Day 1; interleukin‐2, 9 × 106 IU/m2/day i.v. over 24 hours, on Days 1–4; and interferon‐α, 5 × 106 IU/m2/day subcutaneously, on Days 1–5, every 3 weeks. Twelve patients did not have measurable disease. All patients were evaluable for toxicity and survival.RESULTSClinical responses were observed in 14 of 36 patients (38.9%) with measurable disease, including 13 partial responses (36.1%) and 1 complete response (2.8%). Complete pathologic responses were noted in 4 patients (11.1%). Toxicity, although severe, was manageable and typically short‐lived. There were no treatment‐related deaths reported. At a median follow‐up of 31 months, 38 of the 48 patients (79.2%) were alive and 31 patients (64.6%) remained free of disease progression.CONCLUSIONSNeoadjuvant biochemotherapy appears to have promising activity in patients with Stage III melanoma. A larger multicenter study currently is underway to explore this approach further. Cancer 2002;94:470–6. © 2002 American Cancer Society.
Molecular markers of prognosis in astrocytic tumors
Authors: Rasheed Ahmed , Herndon James E. , Stenzel Timothy T. , Raetz Jacqueline G. M. , Kendelhardt Jason , Friedman Henry S. , Friedman Allan H. , Bigner Darell D. , Bigner Sandra H. , McLendon Roger E. 
Published: August 2002

AbstractBACKGROUNDAstrocytoma is a primary brain tumor that affects 20,000 Americans each year. To date, only age and histologic grade stand out as independent predictors of survival. There is now increased interest in the use of molecular markers as objective standards against which to establish diagnosis and grade.METHODSThe study evaluated human glioma tumor suppressor genes and associated loci in fresh snap‐frozen gliomas from 63 males and 37 females, with a median age of 42 years, including 19 low‐grade astrocytomas. The tumor samples were selected so that about equal numbers of glioblastomas from younger and older patients were represented in the series. Methods for suppressor gene and genetic loci evaluation included loss of heterozygosity (LOH) analysis, multiplex polymerase chain reaction analysis, and gene sequencing.RESULTSLow‐grade astrocytomas had the least number of molecular abnormalities. LOH on 9p and/or CDKN2A deletion occurred more often in glioblastomas (P < 0.001), LOH on 17p/TP53 mutations occurred more frequently in anaplastic astrocytomas (AAs; P = 0.112), and LOH on 10q/PTEN mutation frequency was similar in glioblastomas and AAs (P < 0.001). Poorer survival was associated significantly with the occurrence of either deletion of p16 (P = 0.031), LOH on 9p (P = 0.016), or LOH on 10q (P = 0.0007). The absence of LOH on 17p and the presence of PTEN mutation were associated marginally with survival. Even though TP53 mutations were more frequent among younger patients with glioblastoma, they had no statistically significant effect on survival after adjustment for age (P = 0.62). In all multivariate models, age and grade were the only significant predictors of survival or were nearly significant predictors of survival.CONCLUSIONSThe results suggest that LOH on 9p and p16 deletions may prove to be objective standards for the diagnosis of patients with high‐grade gliomas, although the absence of these abnormalities is nonprognostic. Cancer 2002;94:2688–97. © 2002 American Cancer Society.DOI 10.1002/cncr.10544
ErbB2 overexpression correlates with increased expression of vascular endothelial growth factors A, C, and D in human breast carcinoma
Authors: Yang Wentao , Klos Kristine , Yang Ying , Smith Terry L. , Shi Daren , Yu Dihua 
Published: August 2002

AbstractBACKGROUNDThe angiogenic factor vascular endothelial growth factor (VEGF)‐A plays an important role in breast cancer progression. However, the involvement of VEGF‐C and VEGF‐D, two newer members of the VEGF family, in breast carcinoma and their relationship with clinicopathologic parameters have not been clearly demonstrated.METHODSIn this study, the expression levels of VEGF‐A, VEGF‐C, and VEGF‐D protein in 107 breast carcinoma cases and 22 nonmalignant breast tissue samples were examined by immunohistochemistry and quantitated by image analysis.RESULTSHigher expression of VEGF‐C and VEGF‐D was found in breast carcinomas than in nonmalignant breast tissue samples. Moreover, expression of VEGF‐A, VEGF‐C, and VEGF‐D was significantly and positively correlated with ErbB2 expression. High levels of VEGF‐A expression were associated with shorter disease‐free survival (DFS). Patients with tumors expressing high levels of VEGF‐C or VEGF‐D showed a notable trend for worse DFS, however, it was not statistically significant. The combination of VEGF‐A and VEGF‐C status predicted survival better than either marker alone.CONCLUSIONSOur study suggests that expression of the angiogenic and lymphangiogenic factors (i.e., VEGFs) might be regulated at least in part by ErbB2. In addition, the combination of VEGF‐A and VEGF‐C status may better predict prognosis of patients with breast carcinoma than VEGF‐A alone. Cancer 2002;94:2855–61. © 2002 American Cancer Society.DOI 10.1002/cncr.10553
Neuronal development in larval chiton Ischnochiton hakodadensis (Mollusca: Polyplacophora)
Authors: Voronezhskaya Elena E. , Tyurin Sergei A. , Nezlin Leonid P. 
Published: August 2002

AbstractChitons are the most primitive molluscs and, thus, a matter of considerable interest for understanding both basic principles of molluscan neurogenesis and phylogeny. The development of the nervous system in trochophores of the chiton Ischnochiton hakodadensis from hatching to metamorphosis is described in detail by using confocal laser scanning microscopy and antibodies raised against serotonin, FMRFamide, and acetylated α‐tubulin. The earliest nervous elements detected were peripheral neurons located in the frontal hemisphere of posthatching trochophores and projecting into the apical organ. Among them, two pairs of unique large lateral cells appear to pioneer the pathways of developing adult nervous system. Chitons possess an apical organ that contains the largest number of neurons among all molluscan larvae investigated so far. Besides, many pretrochal neurons are situated outside the apical organ. The prototroch is not innervated by larval neurons. The first neurons of the developing adult central nervous system (CNS) appear later in the cerebral ganglion and pedal cords. None of the neurons of the larval nervous system are retained in the adult CNS. They cease to express their transmitter content and disintegrate after settlement. Although the adult CNS of chitons resembles that of polychaetes, their general scenario of neuronal development resembles that of advanced molluscs and differs from annelids. Thus, our data demonstrate the conservative pattern of molluscan neurogenesis and suggest independent origin of molluscan and annelid trochophores. J. Comp. Neurol. 444:25–38, 2002. © 2002 Wiley‐Liss, Inc.
Central organization of the electrosensory system in the paddlefish (Polyodon spathula)
Authors: Hofmann Michael H. , Wojtenek Winfried , Wilkens Lon A. 
Published: August 2002

AbstractThe central connections of the electrosensory system were studied in the paddlefish Polyodon spathula by injecting biotinylated dextran amines into the dorsal octavolateral nucleus (DON), the cerebellum, and the mesencephalic tectum. The sole target of primary electrosensory fibers is the ipsilateral dorsal octavolateral nucleus. The principal neurons ascending from this nucleus project to the torus semicircularis, the lateral mesencephalic nucleus, and the mesencephalic tectum. The mesencephalic tectum projects back to the nucleus preeminentialis, which, in turn, projects to the cerebellar auricles and to the DON. The auricles are the main source of parallel fibers in the cerebellar crest ventral to the DON. The DON also receives input from the contralateral DON. These descending feedback loops are very similar to those of other electrosensory fishes. However, the paddlefish is unique in having three mesencephalic targets of electrosensory information. It is the only bony fish known to have extensive projections directly to the mesencephalic tectum and to a lateral mesencephalic nucleus in addition to the torus semicircularis. J. Comp. Neurol. 446:25–36, 2002. © 2002 Wiley‐Liss, Inc.
Callosal connections correlate preferentially with ipsilateral cortical domains in cat areas 17 and 18, and with contralateral domains in the 17/18 transition zone
Authors: Olavarria Jaime F. 
Published: August 2002

AbstractPrevious studies have shown that the distribution of callosal connections in the 17/18 callosal zone of the cat is patchy at a small scale, but the mechanisms that determine this periodic pattern remain unclear. The present study investigated this issue by correlating the distribution of retrogradely labeled callosal cells with the underlying patterns of ocular dominance columns (ODCs) revealed transneuronally after intraocular injections of wheat germ agglutinin‐horseradish peroxidase. The density of labeled callosal cells was found to vary significantly between adjacent territories dominated by different eyes, indicating that the distribution of callosal cells is significantly biased toward domains that are eye specific. Moreover, callosal connections relate to the pattern of ODCs in a rather unique way: callosal cells correlate preferentially with contralateral ODCs within the 17/18 transition zone (TZ), and with ipsilateral ODCs in regions of areas 17 and 18 located outside the TZ. Similar results were obtained in cats raised with strabismus, indicating that the overlap between right and left ODCs present in normal cats does not influence the correlation between callosal neurons and ODCs. The results are consistent with the hypothesis that callosal linkages are stabilized during development by interhemispheric correlated activity driven by bilateral projections from temporal retina. It is proposed that developmental constraints imposed by both this retinally driven mechanism and the pattern of ODCs are likely to determine not only the association of callosal clusters with specific sets of ODCs, but also important aspects of the functional characteristics of the callosal pathway in cat striate cortex. J. Comp. Neurol. 433:441–457, 2001. © 2001 Wiley‐Liss, Inc.
Catecholamine‐containing cells in the central nervous system and periphery of Aplysia californica
Authors: Croll Roger P. 
Published: August 2002

AbstractPrevious studies have suggested the presence of numerous catecholamine‐containing cells in both the central ganglia and peripheral tissues of Aplysia, but they often offered conflicting or incomplete accounts of numbers, locations, and morphologies. The current study combines aldehyde‐induced histofluorescence and tyrosine hydroxylase‐like immunoreactivity together with confocal microscopy to provide details of these cells. Approximately 35–50 neurones in the cerebral ganglia, 4–8 neurones in the pedal ganglia, 5 neurones in the buccal ganglia, and numerous small fibres in various nerve trunks exhibited both immunoreactivity and aldehyde‐induced fluorescence. Approximately 20 cells in the pedal ganglia and 4 cells in the buccal ganglia exhibited only immunoreactivity whereas 15–20 neurons in the cerebral ganglia exhibited only aldehyde‐induced fluorescence. No somata in the pleural or abdominal ganglia exhibited aldehyde‐induced fluorescence or immunoreactivity. Both aldehyde‐induced histofluorescence and immunoreactivity also labelled what appeared to be two classes of catecholamine‐containing cells in the gill, siphon, oesophagus, rhinophore, tentacle, and reproductive organs. The more numerous, but smaller cells had subepithelial somata and processes penetrating the overlying body wall, thus suggesting a sensory function. Another class of neurones had larger somata, often located more deeply within the tissue, and occasionally appeared to be multipolar. Processes from these various peripheral cells appeared to comprise the major component of afferent fibres and to form an extensive peripheral plexus, often associated with various muscles. The morphologies of the peripheral cells thus suggest involvement in both local and centrally mediated reflexes and responses, but additional studies must test such hypothesised functions and determine the sensory modalities that the cells mediate. J. Comp. Neurol. 441:91–105, 2001. © 2001 Wiley‐Liss, Inc.
Three‐dimensional reconstruction of scleral cold thermoreceptors of the cat eye
Authors: Heppelmann Bernd , Gallar Juana , Trost Brigitte , Schmidt Robert F. , Belmonte Carlos 
Published: August 2002

AbstractSensory endings that respond to local cooling were identified electrophysiologically in the cat's sclera. Functionally identified scleral thermal fibers were then used to analyze the structural characteristics of cold receptor endings. Four Aδ units sensitive to controlled cooling of their scleral receptive fields were recorded. The receptive areas were mapped, demarcated with pins and examined electron microscopically using extensive three‐dimensional reconstructions. The supporting tissue within the receptive areas of cold units consisted of dense collageneous tissue with a small number of blood vessels that were either veins or capillaries. Aδ nerve fibers were found within these tissue blocks presumably corresponding with cold sensitive fibers. Small nerves and single nerve fibers devoid of a perineurium were found in all parts of the tissue, only occasionally passing a blood vessel. The terminal portions showed axonal swellings all along the unmyelinated segment filled with mitochondria, glycogen particles, and some vesicles. About 30% of the terminal axonal membrane is not covered by Schwann cells. In the unmyelinated distal portion, the mitochondrial content ranged from 0.012 to 0.038 μm3 mitochondrial volume per μm2 nerve fiber membrane. In comparison with sensory endings in the cat's knee joint, cold receptors in the cat sclera showed many similarities in their three‐dimensional structure with polymodal nociceptor endings of the knee joint but contain less mitochondria. This suggests that cold sensory endings do not require specialized cellular processes for the transduction of cold stimuli, as is the case for multimodal transduction and sensitization in the terminal portion of polymodal nociceptors. J. Comp. Neurol. 441:148–154, 2001. © 2001 Wiley‐Liss, Inc.
CD45‐assisted PanLeucogating for accurate, cost‐effective dual‐platform CD4+ T‐cell enumeration
Authors: Glencross Deborah , Scott Lesley E. , Jani Ilesh V. , Barnett David , Janossy George 
Published: August 2002

AbstractBACKGROUNDNorth American and European guidelines for dual‐platform (DP) flow cytometry recommend absolute CD4 T‐cell counts to be calculated from two parameters: the absolute lymphocyte counts obtained on a hematology analyzer and the percentages of CD4+ cells among lymphocytes (CD4%/lympho) obtained by flow cytometry. Nevertheless, the identification of lymphocytes is error‐prone: a poor match between these common denominators in the two systems is the main source of inaccuracy. In contrast, total leucocyte counts (white cell counts [WCC]) and CD4% among the gated CD45+ leucocytes (CD4%/leuco) can be determined with greater accuracy. Methods: We introduced “PanLeucogating,” i.e., we used total leucocytes as the common denominator for improving the precision of DP absolute CD4 counting. Correlations and Bland‐Altman tests were used for statistical analysis. Results: First, 22 stabilized blood product samples were provided by U.K. National External Quality Assessment Scheme (NEQAS) and a higher accuracy and precision of CD4 counts were documented using PanLeucogating compared with lymphocyte gating. Next, 183 fresh and 112 fixed (TransFix) whole blood samples were used to compare DP methods and single‐platform (SP) methodology, including both volumetric and bead‐based techniques. A particularly high correlation and comparable precision of absolute CD4 counts were observed between the SP volumetric method and DP PanLeucogating (R2 = 0.990; bias 6 ± SD 17%). The SP volumetric method showed lower levels of agreement with the DP lymphocyte gating (R2 = 0.758; bias 14 ± SD 51%) and with the SP bead‐based method (R2 = 0.923; bias 4 ±SD 31%). Conclusions: These observations show that DP leucocyte counts (WCC) should replace lymphocyte counts as the “common denominator” although CD4%/lympho values can, as an extra step, be also provided readily if requested. When coupled with quality control for WCC on hematology analyzers, the DP method with CD45 PanLeucogating represents a robust CD4 T‐cell assay that is as accurate as the SP volumetric technique. This DP method uses only two, CD45 and CD4, antibody reagents and can be run on any pair of hematological analyzer plus flow cytometer. Cytometry (Clin. Cytometry) 50:69–77, 2002. © 2002 Wiley‐Liss, Inc.
Selection of lymphocyte gating protocol has an impact on the level of reliability of T‐cell subsets in aging specimens
Authors: Bergeron M. , Nicholson J.K.A. , Phaneuf S. , Ding T. , Soucy N. , Badley A.D. , Hawley Foss N.C. , Mandy F. 
Published: August 2002

AbstractBACKGROUNDIn the past decade, human immunodeficiency virus (HIV) lymphocyte immunophenotyping has evolved significantly. New fluorochromes, new multicolor reagents, enhanced instruments, and the capacity to provide absolute cell counts using the single‐platform technique have all contributed to the reliability of T‐cell subset measurements. In this study, four gating protocols were evaluated to select the most robust method for T‐cell subset enumeration. Methods: Peripheral blood specimens from 21 HIV+ and 20 HIV− individuals were monitored up to 96 h. Aliquots of specimens were stored at room temperature and analyzed at 6 (baseline), 48, 72, and 96 h. Aliquots were stained with CD45‐fluorescein isothiocyanate (FITC)/CD3PC5/CD4RD1/CD8ECD. Data analysis was performed with all four gating protocols. Results: Only with fresh blood did all protocols provide similar results. From samples that were 48 h old, the choice of gating strategy had a dramatic impact on immunophenotyping results. The largest deviations from baseline values occurred at 96 h and gating protocols that included dual light scatter gates provided the greatest shift of T‐cell subset values over time. The gating protocols that were based exclusively on cell lineage‐specific gates gave the most robust T‐cell values up to 96 h. Conclusion: By selecting the appropriate gating protocol, the temporal integrity of specimens can be extended up to 4 days. Cytometry (Clin. Cytometry) 50:53–61, 2002. © 2002 Wiley‐Liss, Inc.
Malignant pleural effusions due to small‐cell lung carcinoma: A cytologic and immunocytochemical study
Authors: Chhieng David C. , Ko Ellen C. , Yee Herman T. , Shultz Jane J. , Dorvault Christine C. , Eltoum Isam A. 
Published: August 2002

AbstractPatients with small‐cell lung carcinoma (SCLC) rarely present with pleural effusions. Based on morphology alone, recognition of SCLC in effusion cytology may be challenging because of the resemblance of neoplastic cells to lymphocytes. Immunocytochemistry may be helpful in its diagnosis. The objective of this study was to review the morphology and evaluate the use of immunocytochemistry in diagnosing SCLC in pleural fluids. Patients with SCLC who presented with pleural effusions were identified during a 6‐yr period. The cytology and medical records were reviewed. Formalin‐fixed, paraffin‐embedded cell blocks of fluid specimens were immunostained with neuroendocrine markers (chromogranin A and synatophysin), cytokeratin 20 (CK20), and thyroid transcription factor‐1 (TTF‐1). The latter is a nuclear transcription protein that is expressed in normal respiratory epithelium and also in more than 90% of SCLCs. Of the 256 patients diagnosed with SCLC during the study period, 8 (2.7%) patients (3 females and 4 males, age range from 56–85 yr) also developed pleural effusions. One patient had 2 fluid specimens during the course of their disease, giving a total of 9 specimens. Four specimens had a positive cytologic diagnosis of SCLC, and 2 were initially diagnosed as suspicious for SCLC. The remaining 3 specimens were negative for SCLS. The specimens with a positive or suspicious diagnosis showed single and aggregates of small to medium‐sized single cells with a high nuclear:cytoplasmic (N:C) ratio, round to angulated nuclei, and salt‐and‐pepper chromatin. Nuclear molding was also noted. Five out of 6 (83%) specimens with a positive or suspicious diagnosis of SCLC were positive for both chromogranin A and TTF‐1. Synaptophysin was positive in 3 of 6 (50%) positive or suspicious cases. None of the cases were positive for CK20. All cases with a negative cytologic diagnosis were negative for chromogranin A, synatophysin, CK20, and TTF‐1. In conclusion, patients with SCLC rarely present with pleural effusions. The cytology of SCLC is characteristic. The use of immunocytochemistry, particularly with antibodies to chromogranin A, TTF‐1, and CK 20, aids in the differential diagnosis. Diagn. Cytopathol. 25:356–360, 2001. © 2001 Wiley‐Liss, Inc.