bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost‐effectiveness of staging computed tomography of the chest in patients with T2 soft tissue sarcomas
Authors: Porter Geoffrey A. , Cantor Scott B. , Ahmad Syed A. , Lenert Jeffrey T. , Ballo Matthew T. , Hunt Kelly K. , Feig Barry W. , Patel Shreyaskumar R. , Benjamin Robert S. , Pollock Raphael E. , Pisters Peter W. T. 
Published: August 2002

AbstractBACKGROUNDPublished practice guidelines recommend routine chest computed tomography (CT) scanning as part of the staging evaluation for patients with T2 soft tissue sarcomas (STS), although there is no direct evidence to support this practice. The objective of this study was to determine the yield and cost‐effectiveness of routine versus selective chest CT scanning for the staging of patients with T2 STS and to identify any subgroups for whom a more selective approach to chest CT scanning could be considered.METHODSSix hundred consecutive patients with primary, nonthoracic, T2 (> 5 cm) STS underwent both chest X‐ray (CXR) and chest CT scanning to evaluate the presence of pulmonary metastatic disease (M1). The authors constructed a decision tree that modeled the outcomes of diagnostic testing for two hypothetical diagnostic strategies: 1) routine chest CT (rCT) or 2) CXR and selective chest CT (sCT). The yield and cost of each strategy were determined; the incremental cost‐effectiveness ratio (ICER) was calculated as the cost per additional patient with pulmonary metastases identified by rCT versus sCT.RESULTSThe yield of rCT was higher than that of sCT (M1 disease identified in 19.2% vs. 16.0% of patients, respectively), but rCT was more costly ($1301 vs. $418 per patient, respectively). The ICER of rCT compared with sCT was $27,594 per patient identified with pulmonary metastasis. The expected yields, costs, and ICERs of the diagnostic strategies varied across patient subgroups based on grade, anatomic site, and tumor size.CONCLUSIONSFor patients with T2 STS, rCT was most cost‐effective in patients with high‐grade lesions or extremity lesions. The findings of this study do not support the routine use of chest CT scanning in all patients with T2 STS. Cancer 2002;94:197–204. © 2002 American Cancer Society.
Medullary thyroid carcinoma as part of a multiple endocrine neoplasia type 2B syndrome
Authors: Leboulleux S. , Travagli J. P. , Caillou B. , Laplanche A. , Bidart J. M. , Schlumberger M. , Baudin E. 
Published: August 2002

AbstractBACKGROUNDMultiple endocrine neoplasia type 2B (MEN 2B) is an exceptional syndrome, for which the optimal age of thyroidectomy is poorly established and the course of medullary thyroid carcinoma (MTC) is ill‐defined.PATIENTSAll the 18 patients with a MEN 2B syndrome examined at the Institut Gustave Roussy were included in a single‐center retrospective study.RESULTSThere were 9 men and 9 women with a mean age of 13 years (range, 2–27 years) at diagnosis. The diagnosis of MTC was based on the presence of a thyroid nodule or involved neck lymph nodes and on dysmorphic features of MEN 2B in 60% and 40% of the cases, respectively. The classic M918T mutation in exon 16 was found in the 16 patients in whom it was investigated. At diagnosis, 2 patients had Stage I MTC, 15 patients had Stage III, and 1 patient had Stage IV disease. T1 MTC was found in 4 patients aged 2.1–3.7 years. However, two of these patients already had N1 disease. One patient with Stage I MTC, aged 3.4 years and 2 patients with Stage III disease, aged 14 and 25 years, had undetectable basal calcitonin (CT) after initial surgery. During follow‐up, basal CT became detectable in one of three patients. Among the 15 other patients with an elevated postoperative CT level, metastases were demonstrated in 5 patients after a mean follow‐up of 2 years. Five patients died, three of MTC, one of the MEN 2B syndrome, and one of intercurrent disease. Five‐ and 10‐year overall survival rates were 85% and 75%, respectively.CONCLUSIONSThis study confirms the need for early treatment of MTC in patients with the MEN 2B syndrome, preferably within the first 6 months of life. The phenotype of MTC occurring in the MEN 2B syndrome was not more aggressive than sporadic MTC or MTC occurring in other familial syndromes. Cancer 2002;94:44–50. © 2002 American Cancer Society.
Inducing oral immune regulation of hepatitis B virus envelope proteins suppresses the growth of hepatocellular carcinoma in mice
Authors: Gotsman Israel , Alper Ruslana , Klein Athalia , Rabbani Elazar , Engelhardt Dean , Ilan Yaron 
Published: August 2002

AbstractBACKGROUNDHepatitis B virus (HBV)‐associated hepatocellular carcinoma (HCC) expresses hepatitis B surface antigen (HBsAg) on its cell surface, and this may serve as a tumor‐associated antigen. It was shown previously that adoptive transfer of immunity against HBsAg facilitates the suppression of experimental human HCC‐expressing HBsAg in athymic mice. The authors recently showed that it was possible to augment the anti‐HBV immune response through induction of oral immune regulation for HBV‐associated antigens. The objective of this study was to evaluate the effect of oral immune regulation for HBV antigens on the growth of HBsAg‐expressing HCC.METHODSRecipient athymic Balb/c mice were irradiated sublethally and injected with 107 human hepatoma cells followed by the adoptive transfer of 2 × 106 splenocytes from donor mice. Four groups of donor Balb/c mice were studied: Two groups were immune modulated through oral administration of HBV antigens (HBsAg, PreS1, and Pre S2) or bovine serum albumin (BSA). Two control groups were immunized for HBsAg and fed HBV antigens or BSA. Recipient mice were followed for tumor volume and serum α‐fetoprotein (αFP) levels. The humoral immune response was determined by measuring serum HBs antibodies. HBV specific T‐cell immune modulation was assessed in vitro by HBV specific T‐cell proliferation and interferon γ (IFNγ) ELISPOT assays as well as cytokine expression by reverse transcriptase‐polymerse chain reaction assays.RESULTSThe adoptive transfer of orally immune modulated HBV splenocytes induced complete tumor suppression in recipient mice compared with control mice transplanted with nonimmune modulated cells (BSA), which showed significant tumor growth (serum αFP levels were 3.5 ng/mL and 2320.0 ng/mL, respectively). Control mice transplanted with anti‐HBs immunized cells (with or without oral immune modulation) manifested similar tumor suppression (3.5 ng/mL and 0.5 ng/mL, respectively). Immunoregulation for HBV antigens augmented the HBV specific T‐cell immune response, as manifested by an increase in HBV specific T‐cell proliferation and IFNγ ELISPOT assays in mice orally immune regulated with HBV proteins compared with naïve mice. Tumor suppression was mediated through increased IFNγ production in immune regulated and immunized mice.CONCLUSIONSThe induction of oral immune regulation for HBV antigens modulated the antitumor immune response, thus suppressing the growth of HCC in mice. This effect was mediated by the enhancement of anti‐HBV specific T‐cell immunity. Cancer 2002;94:406–14. © 2002 American Cancer Society.
Impaired platelet aggregation in melanoma patients treated with interferon‐α‐2b adjuvant therapy
Authors: Gutman Haim , Schachter Jacob , Stopel Ella , Gutman Roee , Lahav Judith 
Published: August 2002

AbstractBACKGROUNDHigh‐dose interferon (INF)‐ α‐2b is the only Food and Drug Administration‐approved adjuvant treatment for patients with melanoma who are at high risk of recurrence. Although circumstantial evidence points to a potentially harmful effect of INF‐α‐2b on platelet function, to the authors' knowledge this has never been studied in humans.METHODSThe study group was comprised of patients who had undergone surgery for melanoma and were free of disease but at a high risk of recurrence. All patients were candidates for adjuvant INF treatment (high‐dose) and were undergoing routine evaluation to which platelet aggregation was added. Aggregation was triggered in standard fashion with adenosine diphosphate, epinephrine, collagen, thrombin, arachidonic acid, and ristocetin. Blood samples were drawn immediately before treatment, during the intravenous loading phase, during the subcutaneous maintenance phase, and 3–6 weeks after cessation of treatment. Patients receiving low‐dose, long‐standing INF‐α‐2b treatment also were tested. All results at each phase were compared with those of normal controls.RESULTSIn those patients receiving high‐dose INF‐α‐2b, ristocetin‐induced aggregation did not appear to be affected. However, the response to ≥ 1 of the other agonists was impaired in 5 of 6 samples during loading, 14 of 15 samples during the maintenance phase, and 8 of 13 samples after treatment, compared with only 1 of 8 samples before treatment (P = 0.025, P = 0.002, and P = 0.067, respectively). During treatment with low‐dose INF, platelet function was affected to a lesser extent.CONCLUSIONSINF treatment in melanoma patients appears to be associated with severe impairment of platelet aggregation, which appears to be dose‐dependent and cumulative–dose‐dependent. This is not detectable by the standard coagulation profile. This effect has significant implications in the event of accidental injury or elective surgery. The antiaggregation activity may be the mechanism by which INF delays, reduces, or prevents the formation of melanoma metastases. Cancer 2002;94:780–5. © 2002 American Cancer Society.DOI 10.1002/cncr.10261
Rapid rise of serum prostate specific antigen levels after discontinuation of the herbal therapy PC‐SPES in patients with advanced prostate carcinoma
Authors: Oh William K. , George Daniel J. , Kantoff Philip W. 
Published: August 2002

AbstractBACKGROUNDPC‐SPES is an herbal supplement whose mechanisms of action are poorly understood, but may be estrogenic. The objective of the current report is to describe the effects of discontinuing PC‐SPES treatment in four patients with androgen‐independent prostate carcinoma.METHODSPatient charts were retrospectively reviewed. A MEDLINE search was performed to investigate whether these effects of PC‐SPES had been previously reported.RESULTSFour men whose metastatic prostate carcinoma progressed despite androgen ablation and subsequent PC‐SPES treatment are described. All four patients developed a rapid increase in serum prostate specific antigen (PSA) within one month of stopping PC‐SPES, ranging from 345% to 880%. Two patients increased their PSA levels to 1300% and 1400% after 7 weeks. Compared to the rate of rise of PSA levels prior to and during PC‐SPES therapy, the rise after stopping this treatment was much higher than expected. Clinical symptoms remained relatively stable despite the serologic changes.CONCLUSIONSDiscontinuing PC‐SPES therapy can be associated with a rapid rise in PSA. To the authors' knowledge, this effect has not been reported previously. This effect should be considered in the design of clinical trials as well as in the standard management of androgen‐independent prostate carcinoma patients. Cancer 2002;94:686–9. © 2002 American Cancer Society.DOI 10.1002/cncr.10269
Noradrenergic innervation of the developing and mature visual and motor cortex of the rat brain: A light and electron microscopic immunocytochemical analysis
Authors: Latsari Maria , Dori Ioanna , Antonopoulos John , Chiotelli Maria , Dinopoulos Athanasios 
Published: August 2002

AbstractThe noradrenergic (NA) innervation of the developing and adult visual and motor cortex of the rat was examined with light and electron microscopic immunocytochemistry by using antibodies against dopamine‐β‐hydroxylase. At birth, NA fibers were present in both cortical areas, appearing as two tangential streams, one above and the other below the cortical plate. During the subsequent weeks, these two streams arborized gradually innervating all cortical layers. The adult pattern of distribution was attained by postnatal day 14, but the density of innervation, which was higher in the motor than in the visual cortex, appeared similar to the adult by the end of the third postnatal week. Electron microscopic analysis revealed that a low proportion of NA varicosities (the highest value was 12% in the adult motor cortex in single sections) were engaged in synaptic contact, throughout development, in both areas examined. The overwhelming majority of these synapses were symmetrical, involving predominantly small or medium dendrites. This evidence suggests that transmission by diffusion is the major mode of NA action in the developing and adult cerebral cortex. Noradrenaline released in the rare synaptic junctions may act mainly to reduce the activity of its cortical targets. The results altogether provide morphologic evidence for an involvement of noradrenaline in the development of the neocortex and, along with earlier data on the serotonergic system, indicate that the monoaminergic systems are endowed with a specific anatomic organization in various areas of the brain. J. Comp. Neurol. 445:145–158, 2002. © 2002 Wiley‐Liss, Inc.
Distribution and morphology of transgenic mouse oligodendroglial‐lineage cells following transplantation into normal and myelin‐deficient rat CNS
Authors: Schiff Rolf , Rosenbluth Jack , Dou Wen‐Kai , Liang Wei‐Lan , Moon David 
Published: August 2002

AbstractGlial cells from neonatal MβP5 transgenic mice, which express bacterial β‐galactosidase (lacZ) under control of the myelin basic protein (MBP) promoter (Gow et al, 1992), were transplanted into the spinal cord or cerebral hemisphere of immunosuppressed normal and myelin‐deficient (md) rats in order to assess the ability of the donor cells to survive, migrate, and differentiate within normal compared with myelin‐deficient central nervous system (CNS). LacZ+ cells were detected as early as 6–7 days after transplantation into the low thoracic cord and by 10 days had spread rostrally to the brainstem and caudally to the sacral spinal cord. Initially, compact lacZ+ cells, lacking processes, were found associated with small blood vessels and with the glia limitans. Cells of this type persisted throughout the experiment. Later, lacZ+ cells with processes were seen along fiber tracts in the dorsal columns and, after intracerebral injection, subjacent to ventricular ependyma, as well as scattered in cerebral white and gray parenchyma. The extent of spread was comparable in md and normal rats, but in the md group, the success rate was higher, and more cells differentiated into process‐bearing oligodendrocytes. Acceptance of xenografts in immunosuppressed recipients equaled that of allografts. The overall spread of grafted cells exceeded that of injected charcoal, indicating active migration. In contrast to earlier studies that identified oligodendrocytes based on morphology alone, this study has allowed us to identify and track oligodendrocytes based on myelin gene expression. We show some oligodendrocytes whose morphology is consistent with classical morphological descriptions, some that resemble astrocytes, and a class of compact perivascular oligodendrocyte‐lineage cells that we suggest are migratory. J. Comp. Neurol. 446:46–57, 2002. © 2002 Wiley‐Liss, Inc.
Cannabinoid receptors are absent in insects
Authors: McPartland John , Di Marzo Vincenzo , De Petrocellis Luciano , Mercer Alison , Glass Michelle 
Published: August 2002

AbstractThe endocannabinoid system exerts an important neuromodulatory role in mammals. Knockout mice lacking cannabinoid (CB) receptors exhibit significant morbidity. The endocannabinoid system also appears to be phylogenetically ancient—it occurs in mammals, birds, amphibians, fish, sea urchins, leeches, mussels, and even the most primitive animal with a nerve network, the Hydra. The presence of CB receptors, however, has not been examined in terrestrial invertebrates (or any member of the Ecdysozoa). Surprisingly, we found no specific binding of the synthetic CB ligands [3H]CP55,940 and [3H]SR141716A in a panel of insects: Apis mellifera, Drosophila melanogaster, Gerris marginatus, Spodoptera frugiperda, and Zophobas atratus. A lack of functional CB receptors was confirmed by the inability of tetrahydrocannabinol (THC) and HU210 to activate G‐proteins in insect tissues, utilizing a guanosine‐5′‐O‐(3‐[35]thio)‐triphosphate (GTPγS) assay. No orthologs of human CB receptors were located in the Drosophila genome, nor did we find orthologs of fatty acid amide hydrolase. This loss of CB receptors appears to be unique in the field of comparative neurobiology. No other known mammalian neuroreceptor is understood to be missing in insects. We hypothesized that CB receptors were lost in insects because of a dearth of ligands; endogenous CB ligands are metabolites of arachidonic acid, and insects produce little or no arachidonic acid or endocannabinoid ligands, such as anandamide. J. Comp. Neurol. 436:423–429, 2001. © 2001 Wiley‐Liss, Inc.
Neurotrophism without neurotropism: BDNF promotes survival but not growth of lesioned corticospinal neurons
Authors: Lu Paul , Blesch Armin , Tuszynski Mark H. 
Published: August 2002

AbstractNeurotrophic factors exert many effects on the intact and lesioned adult central nervous system (CNS). Among these effects are prevention of neuronal death (neurotrophism) and promotion of axonal growth (neurotropism) after injury. To date, however, it has not been established whether survival and axonal growth functions of neurotrophins can be independently modulated in injured adult neurons in vivo. To address this question, the ability of brain‐derived neurotrophic factor (BDNF) to influence corticospinal motor neuronal survival and axonal growth was examined in two injury paradigms. In the first paradigm, a survival assay, adult Fischer 344 rats underwent subcortical lesions followed by grafts to the lesion cavity of syngenic fibroblasts genetically modified to secrete high amounts BDNF or, in control subjects, the reporter gene green fluorescent protein. In control subjects, only 36.2 ± 7.0% of the retrogradely labeled corticospinal neurons survived the lesion, whereas 89.8 ± 5.9% (P < 0.001) of the corticospinal neurons survived in animals that received BDNF‐secreting grafts. However, in an axonal growth assay, BDNF‐secreting cell grafts that were placed into either subcortical lesion sites or sites of thoracic spinal cord injury failed to elicit corticospinal axonal growth. Despite this lack of a neurotropic effect on lesioned corticospinal axons, BDNF‐secreting cell grafts placed in the injured spinal cord significantly augmented the growth of other types of axons, including local motor, sensory, and coerulospinal axons. Immunolabeling for tyrosine kinase B (trkB) demonstrated that BDNF receptors were present on corticospinal neuronal somata and apical dendrites but were not detected on their projecting axons. Thus, single classes of neurons in the adult CNS appear to exhibit disparate survival and growth sensitivity to neurotrophic factors, potentially attributable at least in part to differential trafficking of neurotrophin receptors. The possibility of tropic/trophic divergence must be considered when designing strategies to promote CNS recovery from injury. J. Comp. Neurol. 436:456–470, 2001. © 2001 Wiley‐Liss, Inc.
Quantitative analyses of anatomical and electrotonic structures of local spiking interneurons by three‐dimensional morphometry in crayfish
Authors: Hikosaka Ryou , Takahata Masakazu 
Published: August 2002

AbstractWe quantitatively investigated the three‐dimensional structure of the dendrites of local spiking interneurons using a confocal laser scanning microscope in the terminal abdominal ganglion of crayfish. We also studied their passive membrane properties electrophysiologically using the single‐electrode current clamp techniques to analyze their electrotonic structure. All of the local spiking interneurons examined in this study lacked distinctive axonal structure and had a monopolar cell body that was connected with a fine primary process to a thick main segment. Numerous fine secondary processes projected from the main segment in the ganglionic neuropile. The average anatomical length of a secondary process from the main segment to its terminal was 261.9 ± 15.2 μm. The average input resistance and membrane time constant of local spiking interneurons, obtained from their voltage responses to intracellular injection of step current pulses in the main segment, were 15.2 ± 1.6 MΩ and 13.9 ± 1.9 msec, respectively. Calculation of the electrotonic length of dendritic processes based on morphological and physiological data obtained in this study revealed that the average electrotonic length of secondary processes in local spiking interneurons was significantly longer than in local nonspiking interneurons, although both types of local interneurons showed apparently similar anaxonic structure. The steady‐state voltage attenuation factors for the secondary processes of local spiking interneurons were significantly greater than those of local nonspiking interneurons in both centrifugal and centripetal directions. The larger electrotonic structure of local spiking interneurons compared to that of nonspiking interneurons appears to be compensated for by their excitable dendritic membrane. J. Comp. Neurol. 432:269–284, 2001. © 2001 Wiley‐Liss, Inc.
A role for cingulate pioneering axons in the development of the corpus callosum
Authors: Rash Brian G. , Richards Linda J. 
Published: August 2002

AbstractIn many vertebrate and invertebrate systems, pioneering axons play a crucial role in establishing large axon tracts. Previous studies have addressed whether the first axons to cross the midline to from the corpus callosum arise from neurons in either the cingulate cortex (Koester and O'Leary [1994] J. Neurosci. 11:6608–6620) or the rostrolateral neocortex (Ozaki and Wahlsten [1998] J. Comp. Neurol. 400:197–206). However, these studies have not provided a consensus on which populations pioneer the corpus callosum. We have found that neurons within the cingulate cortex project axons that cross the midline and enter the contralateral hemisphere at E15.5. By using different carbocyanine dyes injected into either the cingulate cortex or the neocortex of the same brain, we found that cingulate axons crossed the midline before neocortical axons and projected into the contralateral cortex. Furthermore, the first neocortical axons to reach the midline crossed within the tract formed by these cingulate callosal axons, and appeared to fasciculate with them as they crossed the midline. These data indicate that axons from the cingulate cortex might pioneer a pathway for later arriving neocortical axons that form the corpus callosum. We also found that a small number of cingulate axons project to the septum as well as to the ipsilateral hippocampus via the fornix. In addition, we found that neurons in the cingulate cortex projected laterally to the rostrolateral neocortex at least 1 day before the neocortical axons reach the midline. Because the rostrolateral neocortex is the first neocortical region to develop, it sends the first neocortical axons to the midline to form the corpus callosum. We postulate that, together, both laterally and medially projecting cingulate axons may pioneer a path for the medially directed neocortical axons, thus helping to guide these axons toward and across the midline during the formation of the corpus callosum. J. Comp. Neurol. 434:147–157, 2001. © 2001 Wiley‐Liss, Inc.