bluuebunny/crossref_metadata_2025 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

BACKGROUND

Published 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.

METHODS

Six 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.

RESULTS

The 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.

CONCLUSIONS

For 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

BACKGROUND

Multiple 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.

PATIENTS

All the 18 patients with a MEN 2B syndrome examined at the Institut Gustave Roussy were included in a single‐center retrospective study.

RESULTS

There 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.

CONCLUSIONS

This 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

BACKGROUND

Hepatitis 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.

METHODS

Recipient 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.

RESULTS

The 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.

CONCLUSIONS

The 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

BACKGROUND

High‐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.

METHODS

The 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.

RESULTS

In 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.

CONCLUSIONS

INF 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

BACKGROUND

PC‐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.

METHODS

Patient charts were retrospectively reviewed. A MEDLINE search was performed to investigate whether these effects of PC‐SPES had been previously reported.

RESULTS

Four 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.

CONCLUSIONS

Discontinuing 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

The 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

Glial 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

The 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

Neurotrophic 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

We 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

In 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.
Layer V in cat primary auditory cortex (AI): Cellular architecture and identification of projection neurons
Authors: Winer Jeffery A. , Prieto Jorge J.
Published: August 2002

The cytoarchitectonic organization and the structure of layer V neuronal populations in cat primary auditory cortex (AI) were analyzed in Golgi, Nissl, immunocytochemical, and plastic‐embedded preparations from mature specimens. The major cell types were characterized as a prelude to identifying their connections with the thalamus, midbrain, and cerebral cortex using axoplasmic transport methods. The goal was to describe the structure and connections of layer V neurons more fully. Layer V has three sublayers based on the types of neuron and their sublaminar projections. Four types of pyramidal and three kinds of nonpyramidal cells were present. Classic pyramidal cells had a long apical dendrite, robust basal arbors, and an axon with both local and corticofugal projections. Only the largest pyramidal cell apical dendrites reached the supragranular layers, and their somata were found mainly in layer Vb. Three types departed from the classic pattern; these were the star, fusiform, and inverted pyramidal neurons. Nonpyramidal cells ranged from large multipolar neurons with radiating dendrites, to Martinotti cells, with smooth dendrites and a primary trunk oriented toward the white matter. Many nonpyramidal cells were multipolar, of which three subtypes (large, medium, and small) were identified; bipolar and other types also were seen. Their axons formed local projections within layer V, often near pyramidal neurons. Several features distinguish layer V from other layers in AI. The largest pyramidal neurons were in layer V. Layer V neuronal diversity aligns it with layer VI (Prieto and Winer [1999] J. Comp. Neurol. 404:332–358), and it is consistent with the many connectional systems in layer V, each of which has specific sublaminar and neuronal origins. The infragranular layers are the source for several parallel descending systems. There were significant differences in somatic size among these projection neurons. This finding implies that diverse corticofugal roles in sensorimotor processing may require a correspondingly wide range of neuronal architecture. J. Comp. Neurol. 434:379–412, 2001. © 2001 Wiley‐Liss, Inc.
GDNF and NGF family members and receptors in human fetal and adult spinal cord and dorsal root ganglia
Authors: Josephson Anna , Widenfalk Johan , Trifunovski Alexandra , Widmer Hans‐Ruedi , Olson Lars , Spenger Christian
Published: August 2002

We describe the expression of mRNA encoding ligands and receptors of members of the GDNF family and members of the neurotrophin family in the adult human spinal cord and dorsal root ganglia (DRG). Fetal human spinal cord and ganglia were investigated for the presence of ligands and receptors of the neurotrophin family. Tissues were collected from human organ donors and after routine elective abortions. Messenger RNA was found encoding RET, GFRα‐1, BDNF, trkB, and trkC in the adult human spinal cord and BDNF, NT‐3, p75, trkB, and trkC in the fetal human spinal cord. The percentage of adult human DRG cells expressing p75, trkA, trkB, or trkC was 57, 46, 29, and 24%, respectively, and that of DRG cells expressing RET, GFRα‐1, GFRα‐2, or GFRα‐3 was 79, 20, 51, and 32%, respectively. GFRα‐2 was expressed selectively in small, GFRα‐3 principally in small and GFRα‐1 and RET in both large and small adult human DRG neurons. p75 and trkB were expressed by a wide range of DRG neurons while trkA was expressed in most small diameter and trkC primarily in large DRG neurons. Fetal DRG cells were positive for the same probes as adult DRG cells except for NT‐3, which was only found in fetal DRG cells. Messenger RNA species only expressed at detectable levels in fetal but not adult spinal cord tissues included GDNF, GFRα‐2, NT‐3, and p75. Notably, GFRα‐2, which is expressed in the adult rat spinal cord, was not found in the adult human spinal cord. J. Comp. Neurol. 440:204–217, 2001. © 2001 Wiley‐Liss, Inc.
GFRα‐1 mRNA in dopaminergic and nondopaminergic neurons in the substantia nigra and ventral tegmental area
Authors: Sarabi Arezou , Hoffer Barry J. , Olson Lars , Morales Marisela
Published: August 2002

Glial cell line‐derived neurotrophic factor (GDNF) is a survival factor for several types of neurons, including dopaminergic (DAergic) neurons. GDNF binds with high affinity to the GDNF family receptor α‐1 (GFRα‐1), which is highly expressed in the midbrain. Using anatomical and lesion techniques, we demonstrated that GFRα‐1 was expressed in DAergic and non‐DAergic neurons in the rat midbrain. Immunohistochemical characterization of GFRα‐1‐expressing neurons indicated that most of the neurons that were immunopositive for the DAergic marker tyrosine hydroxylase (TH) expressed GFRα‐1 in the substantia nigra pars compacta (SNC). In contrast, fewer TH‐containing neurons expressed GFRα‐1 in the substantia nigra pars reticulata (SNR) and the ventral tegmental area (VTA). Depletion of GFRα‐1/TH neurons was observed in the SNC following treatment with the neurotoxin 6‐hydroxydopamine (6‐OHDA); however, GFRα‐1 expression remained in some neurons located in the SNR. The γ‐aminobutyric acid (GABA)ergic nature of GFRα‐1‐expressing neurons located in the SNR, which were resistant to (6‐hydroxydopamine) 6‐OHDA, was established by their expression of glutamic acid decarboxylase (GAD; the synthesizing enzyme for GABA). Further analysis indicated that coexpression of GFRα‐1 and GAD varied in a rostrocaudal gradient in the SNR, substantia nigra pars lateralis (SNL), and VTA. Midbrain DAergic and GABAergic neurons have been previously classified according to their Ca2+ binding protein (CaBP) content; thus, we also sought to investigate the proportion of midbrain GFRα‐1‐expressing neurons containing parvalbumin (PV), calbindin (CB), and calretinin (CR) in the midbrain. Although GFRα‐1 expression was found mainly in CB‐ and CR‐immunoreactive neurons, it was rarely observed in PV‐immunolabeled neurons. Analysis of the proportion of GFRα‐1‐expressing neurons for each CaBP subpopulation indicated the coexistence of GFRα‐1 with CR in the VTA and all subdivisions of the SN; double‐labeled GFRα‐1/CR neurons were distributed in the SNC, SNR, SNL, and VTA. GFRα‐1/CB neurons were also detected in the SNC, SNL, and VTA. Expression of GFRα‐1 in DAergic and non‐DAergic neurons in the rat SN and VTA suggests that GDNF, via GFRα‐1, might modulate DAergic and GABAergic functions in the nigrostriatal, mesolimbic, and nigrothalamic circuits of the adult rat. J. Comp. Neurol. 441:106–117, 2001. Published 2001 Wiley‐Liss, Inc.
Thermomechanical coupling at finite elastic strain: covariant formulation and numerical implementation
Authors: Ibrahimbegovic Adnan , Chorfi Lotfi , Gharzeddine Fadi
Published: August 2002

We present a theoretical formulation of finite strain thermoelasticity in the general setting of manifolds and a very efficient computational framework for its finite element implementation, obtained by generalizing Hill's principal axis methodology. The proposed formulation is further illustrated by a detailed presentation of a 4‐node axisymmetric finite element and numerical simulations. Copyright © 2001 John Wiley & Sons, Ltd.
Unified approach to KdV modulations
Authors: El Gennady A. , Krylov Alexander L. , Venakides Stephanos
Published: August 2002

We develop a unified approach to integrating the Whitham modulation equations. Our approach is based on the formulation of the initial‐value problem for the zero‐dispersion KdV as the steepest descent for the scalar Riemann‐Hilbert problem [6] and on the method of generating differentials for the KdV‐Whitham hierarchy [9]. By assuming the hyperbolicity of the zero‐dispersion limit for the KdV with general initial data, we bypass the inverse scattering transform and produce the symmetric system of algebraic equations describing motion of the modulation parameters plus the system of inequalities determining the number the oscillating phases at any fixed point on the (x, t)‐plane. The resulting system effectively solves the zero‐dispersion KdV with an arbitrary initial datum. © 2001 John Wiley & Sons, Inc.
Droplet spreading: Intermediate scaling law by PDE methods
Authors: Giacomelli Lorenzo , Otto Felix
Published: August 2002

We consider the spreading of a thin droplet of viscous liquid on a plane surface driven by capillarity. The standard lubrication approximation leads to an evolution equation for the film height h that is ill‐posed when the spreading is limited by the no‐slip boundary condition at the liquid‐solid interface due to a singularity at the moving contact line. The most common relaxation of the no‐slip boundary condition removes this singularity but introduces a new physical length scale: the slippage length b. It is believed that this microscopic‐length scale only enters logarithmically in the effective (that is, macroscopic) spreading behavior.

In this paper, we rigorously show that the naively expected spreading rate is indeed only altered by a logarithmic term involving b. More precisely, we prove a scaling law for the diameter of the apparent (that is, macroscopic) support of the droplet in time. This is an intermediate scaling law: It takes an initial layer to “forget” the initial droplet shape, whereas after a long time, the droplet is so thin that its spreading is governed by the physics on the scale b.

Our proof works by deriving suitable estimates for physically relevant integral quantities: the free energy, the length of the apparent support, and their respective rates of change. As opposed to matched asymptotic methods, this PDE approach closely mimics a simple heuristic argument based on the gradient flow structure. © 2002 John Wiley & Sons, Inc.
Distributed data integration by object‐oriented mediator servers
Authors: Risch Tore , Josifovski Vanja
Published: August 2002

Integration of data from autonomous, distributed and heterogeneous data sources poses several technical challenges. This paper overviews the data integration system AMOS II based on the wrapper‐mediator approach. AMOS II consists of: (i) a mediator database engine that can process and execute queries over data stored locally and in several external data sources, and (ii) object‐oriented (OO) multi‐database views for reconciliation of data and schema heterogeneities among sources with various capabilities. The data stored in different types of data sources is translated and integrated using OO mediation primitives, providing the user with a consistent view of the data in all the sources. Through its multi‐database facilities many distributed AMOS II systems can interoperate in a federation. Since most data reside in the data sources, and to achieve high performance, the core of the system is a main‐memory DBMS having a storage manager, query optimizer, transactions, client–server interface, disk backup, etc. The AMOS II data manager is optimized for main‐memory access and is extensible so that new data types and query operators can be added or implemented in some external programming language. The extensibility is essential for providing seamlessaccess to a variety of data sources. Copyright © 2001 John Wiley & Sons, Ltd.
Exploring the evolution of complexity in signaling networks
Authors: Holland John H.
Published: August 2002

Signaling networks are exemplified by systems as diverse as biological cells, economic markets, and the Web. After a discussion of some general characteristics of signaling networks, this article explores the adaptive evolution of complexity in a simple model of a signaling network. The article closes with a discussion of broader questions concerning the evolution of signaling networks. © 2002 Wiley Periodicals, Inc.
Flow cytometric cytotoxicity assay for measuring mammalian and avian NK cell activity
Authors: Vizler Csaba , Nagy Tünde , Kusz Erzsébet , Glavinas Hristos , Duda Ernő
Published: August 2002

Background

Flow‐cytometric assays are convenient alternatives to classic radioactive natural killer (NK) tests. MitoTracker Green FM, a green fluorescent intracellular probe serving originally for staining mitochondria, seemed especially suitable for labeling NK target cells.

Materials and Methods

NK target cells were labeled with MitoTracker Green FM. After incubation with effector spleen cells, cell suspensions were stained with propidium iodide (PI), and flow‐cytometric analysis was performed.

Results

MitoTracker Green FM stained efficiently each cell type we assayed, including resting cells, and it was not released from dead cells. NK assays were set up using mouse spleen effector cells and K562 NK target cells. MitoTracker Green FM and PI double staining allowed a discrimination of live and dead target cells, and the cytotoxicity values were in the expected range. Then the method was applied to a less well‐known chicken model. We found that chicken‐skin fibroblasts had a definite sensitivity to autologous splenic NK cells, sometimes as high as the sensitivity of classic NK targets.

Conclusions

Convenient flow‐cytometric NK tests can be performed by MitoTracker Green FM and PI staining. Using this method, we demonstrated that chicken fibroblasts are sensitive to the cytotoxic effect of autologous NK cells. Cytometry 47:158–162, 2002. © 2002 Wiley‐Liss, Inc.
Analysis of radiation‐induced apoptosis in human lymphocytes: Flow cytometry using Annexin V and propidium iodide versus the neutral comet assay
Authors: Wilkins R.C. , Kutzner B.C. , Truong M. , Sanchez‐Dardon J. , McLean J.R.N.
Published: August 2002

Background

The neutral comet assay was devised to measure double‐stranded DNA breaks, but it has also been used to measure apoptosis based on its characteristic DNA fragmentation patterns. There is still uncertainty about the reliability of this method. By comparing the comet assay with a flow cytometry method that uses Annexin V binding to apoptotic cells, we have provided further evidence for evaluating the usefulness of the comet assay for detecting apoptosis.

Methods

Apoptosis was induced in human peripheral blood mononuclear cells (PBMC) by ionizing radiation and measured using the comet assay and a flow cytometry method that measures Annexin V and propidium iodide (PI) staining.

Results

The Annexin V flow cytometry assay distinguished among early apoptosis, late apoptosis, and an apoptotic or necrotic phase in which the cells were labeled with both Annexin V and PI. The comet assay detected only the latter two phases of apoptosis.

Conclusions

The comet assay is a useful tool for measuring the late stages of apoptosis whereas the Annexin V assay measures higher amounts of apoptosis because it can detect cells in an earlier stage of the apoptotic pathway. Cytometry 48:14–19, 2002. © 2002 Wiley‐Liss, Inc.
Prospective clinical study comparing DNA flow cytometry and HPV typing as predictive tests for persistence and progression of CIN I/II
Authors: Melsheimer Peter , Klaes R. , v. Knebel Doeberitz M. , Bastert G.
Published: August 2002

A cohort of 70 consecutive women at a university hospital colposcopy clinic with untreated CIN I and CIN II (CIN I/II) confirmed by cytology and histology was followed for 1 year in the setting of a prospective trial. In the lesions, the presence of DNA from HPV types was examined by restriction fragment length polymorphism (RFLP) analysis. Aneuploid cell lines were demonstrated by aneuploid histograms generated by high‐resolution DNA flow cytometry. HPV type 16 infection and the existence of aneuploid cell lines proved to be significant risk factors for CIN I/II lesions to persist or progress to CIN III in the 1‐year follow‐up period in the same cohort of patients. The relative risks and 95% confidence intervals (CI) were 1.81 (1.44–2.76) for aneuploid cell lines and 1.74 (1.10–2.76) for HPV type 16 infection in CIN I/II lesions. As a predictive diagnostic test for CIN I/II lesions to persist or progress, the specificity and positive predictive value (PPV) for aneuploid histograms were 100% (CI, 73.5–100%) and 100% (CI, 86.8–100%), respectively. The low sensitivity of 27.3% (CI, 14.9–42.8%) restricted the clinical application of the test, leaving 32 of 44 women with persisting or progressing CINI/II with diploid histograms. HPV type 16 positivity by FRLP had a PPV of 68.4% (CI, 43.5–87.4%) as a prognostic test. Six of 19 HPV 16 infected women showed complete remission of their CIN lesion. A combination of the two tests did not provide any additional information. Cytometry (Comm. Clin. Cytometry) 46:166–171, 2001. © 2001 Wiley‐Liss, Inc.
Evaluation of monensin and brefeldin A for flow cytometric determination of interleukin‐1 beta, interleukin‐6, and tumor necrosis factor‐alpha in monocytes
Authors: Schuerwegh A.J. , Stevens W.J. , Bridts C.H. , De Clerck L.S.
Published: August 2002

Flow cytometry has become a powerful technique to measure intracellular cytokine production in lymphocytes and monocytes. Appropriate inhibition of the secretion of the produced cytokines is required for studying intracellular cytokine expression. The aim of this study was to compare the capacity of cytokine secretion inhibitors, monensin and brefeldin A, in order to trap cytokine production (interleukin‐1 beta [IL‐1β], IL‐6, tumor necrosis factor‐alpha [TNF‐α]) within peripheral blood monocytes. A two‐color flow cytometric technique was used to measure intracellular spontaneous and lipopolysaccharide (LPS)‐stimulated IL‐1β, IL‐6, and TNF‐α production in monocytes (CD14+) of whole blood cultures. The viability of monensin‐treated monocytes was slightly lower than that of brefeldin A‐inhibited monocytes, as measured with propidium iodide (PI). The percentage of IL‐6 and TNF‐α–producing monocytes after 8 h of culture without stimulation revealed significant lower values for monensin‐treated than for brefeldin A‐treated monocytes. The percentages for stimulated cells did not differ. The spontaneous intracellular production in molecules of equivalent soluble fluorochrome units (MESF) of IL‐1β, IL‐6, and TNF‐α after 8 h of culture was higher in brefeldin A than in monensin‐inhibited monocytes. The LPS‐stimulated intracellular production of IL‐1β, IL‐6, and TNF‐α was increased in brefeldin A‐inhibited monocytes. In conclusion, for flow cytometric determination of intracellular monocytic cytokines (IL‐1β, IL‐6, and TNF‐α), brefeldin A is a more potent, effective, and less toxic inhibitor of cytokine secretion than monensin. Cytometry (Comm. Clin. Cytometry) 46:172–176, 2001. © 2001 Wiley‐Liss, Inc.
Human immunodeficiency virus gag and pol‐specific CD8 T cells in perinatal HIV infection
Authors: McCloskey Thomas W. , Haridas Viraga , Pahwa Raj , Pahwa Savita
Published: August 2002

Background:

Binding of fluorochrome‐conjugated MHC class I tetramers is a powerful means to detect antigen‐specific CD8 T lymphocytes. In human immunodeficiency virus (HIV) infection, cellular immune response is essential in curtailing HIV disease progression but gaps persist in our understanding of HIV‐specific cells during the disease course. In this study, we evaluated tetramer binding HIV‐specific CD8 T cells in HIV‐infected children.

Methods:

Fluorescently labeled tetramers for HIV gag and pol were utilized to quantify antigen‐specific cells by flow cytometry using a whole blood labeling method in a cohort of 19 HLA‐A2+ HIV‐ infected children (age range 1 month to 17 years).

Results:

Fourteen children had detectable gag (median 0.4%) and pol (median 0.1%) binding CD8 T cells, three children had gag binding cells only, and two had neither. Numbers of gag and pol binding cells correlated with each other and each correlated independently with total CD8 T cells and total CD4 T cells.

Conclusions:

HIV gag and pol‐specific CD8 T cells are maintained during the chronic phase of HIV infection in children and CD4 lymphocytes appear to be important for sustaining their levels. Cytometry (Comm. Clin. Cytometry) 46:265–270, 2001. © 2001 Wiley‐Liss, Inc.
Cytologic diagnosis of gastrointestinal stromal tumors of the stomach by endoscopic ultrasound‐guided fine‐needle aspiration biopsy: Cytomorphologic and immunohistochemical study of 12 cases
Authors: Gu Mai , Ghafari Sofia , Nguyen Phuong Thivan , Lin Fritz
Published: August 2002

Gastrointestinal stromal tumor (GIST) is an uncommon tumor, which was usually diagnosed by endoscopic biopsy or surgical resection. This study evaluated the efficacy and accuracy of endoscopic ultrasound (EUS) ‐guided fine‐needle aspiration (FNA) biopsy in the diagnosis of GIST and reported its cytomorphologic features. Twelve patients with gastric GIST were diagnosed through EUS‐guided FNA. Immediate on‐site evaluation and cytologic diagnoses were given in nine cases (75.0%) with an average of three passes. Cell blocks provided diagnostic material in three cases (25.0%). Spindle cells were present in the cytologic material in all cases. Two patients had subsequent surgical resections. Immunohistochemical (IHC) studies performed in cell blocks and two surgical specimens all supported the original diagnoses. In the two cases with surgical resections, IHC results in cell blocks were similar to that in the resected specimens. This study demonstrated that when combining smears and cell blocks, EUS‐guided FNA is accurate and efficient in the diagnosis of GIST. IHC reactivity in cell blocks correlated with that of the main tumors. Diagn. Cytopathol. 25:343–350, 2001. © 2001 Wiley‐Liss, Inc.
Fine‐needle aspiration cytology of benign and malignant adenomyoepithelioma: Report of two cases
Authors: Kurashina Masanori
Published: August 2002

Cytological features of a malignant spindle‐cell variant and a benign tubular variant of adenomyoepithelioma were examined to improve diagnosis of this tumor. Fine‐needle aspiration cytology, of both a malignant and a benign case, characterized cellular and cohesive cell clusters composed of epithelial and myoepithelial cells. The smears of the malignant case were rich in spindle‐shaped myoepithelial cells, admixed with a few epithelial cells. In about a fourth of the clusters, atypical cells with enlarged hyperchromatic nuclei and prominent nucleoli comprised more than 20% of cells. The smears of the benign case were composed of tubular epithelial cells surrounding one to several layers of myoepithelial cells with clear cytoplasm. Mild atypia was occasionally noticed. A review of the literature showed that a cytological diagnosis of malignancy is not warranted, if nuclear atypia is not generally severe. Focal severe atypia is not definitively indicative of benignity or malignancy. Diagn. Cytopathol. 2002;26:29–34. © 2002 Wiley‐Liss, Inc.
Diagnosis of histoplasmosis in urine cytology: Reactive urothelial changes, a diagnostic pitfall. Case report and literature review of urinary tract infections
Authors: Mukunyadzi Perkins , Johnson Michael , Wyble Joseph G. , Scott Margie
Published: August 2002

Histoplasmosis not uncommonly causes systemic infection, particularly in immunocompromised patients. In systemic infection, the urinary tract is often involved, although the diagnosis of histoplasmosis in urine cytologic specimens has never been reported. Urinary tract histoplasmosis may present with gross hematuria, raising clinical suspicion for malignancy. The index case presented with intermittent gross hematuria, suprapubic pain, significant weight loss, hoarse voice, and a painful tongue ulcer. Examination of the patient revealed an ulcerated tongue lesion, an anal ulcer, a polypoid lesion on the vocal cord, and cystoscopic examination of the urinary bladder revealed erythematous patchy areas. Surgical biopsy sections from the vocal cord and tongue lesion were diagnostic of histoplasma infection. Urine cytologic examination showed atypical urothelial cells suspicious for malignancy. However, fungal stains performed on the urine specimen showed histoplasma organisms. We conclude that with a high index of suspicion, and the use of special stains, histoplasma organisms can be identified in urine. Diagn. Cytopathol. 2002;26:243–246. © 2002 Wiley‐Liss, Inc.
Discrete epithelioid cells: Useful clue to Hodgkin's disease cytodiagnosis
Authors: Iyengar Krishnan R. , Mutha Sucheeta
Published: August 2002

Diagnosis of Hodgkin's disease is made with more confidence than diagnosis of non‐Hodgkin's lymphoma on cytology. This study was undertaken to describe the presence of granulomas and a new cytologic feature, discrete epithelioid cells (DECs), in smears from Hodgkin's disease. Fine‐needle aspiration smears from 39 cases of biopsy‐proven Hodgkin's disease, collected over a period of 43 months, were reviewed. Epithelioid granulomas were seen in 38.5% of the smears. DECs, which were noted in 70% of the cases, may be useful in raising the suspicion of Hodgkin's disease when other features are not evident; their presence should encourage the cytopathologist to obtain aspirations from other lymph nodes. Diagn. Cytopathol. 2002;26:142–144; DOI 10.1002/dc.10080 © 2002 Wiley‐Liss, Inc.