bluuebunny/crossref_metadata_2025 huggingface dataset:
A phase 2 study of a fixed combination of uracil and ftorafur (UFT) and leucovorin given orally in a 3‐times‐daily regimen to treat patients with recurrent metastatic breast cancer
Authors: Hortobagyi Gabriel N. , Heim William , Hutchins Laura , Rivera Edgardo , Mason Bernard , Booser Daniel J. , Kirshner Jeffrey
Published: January 2010

BACKGROUND:

A combination of uracil and ftorafur (UFT) was developed to combine the cytotoxic effects of 5‐fluorouracil (5‐FU) with convenient oral dosing. Leucovorin was combined with UFT to further potentiate the effect of 5‐FU on tumor cells. Orally administered UFT and leucovorin provided higher peak plasma concentrations of 5‐FU and prolonged therapeutic 5‐FU concentrations compared with continuous infusion of 5‐FU.

METHODS:

Ninety‐one patients with metastatic breast cancer who had been previously treated with anthracyclines and/or taxanes were treated with UFT and leucovorin, given orally, for the first 28 days of a 35‐day cycle. The total daily dose of UFT was 300 mg/m2, administered in 3 doses of 100 mg/m2 each every 8 hours. The primary endpoint was time to disease progression (TTP). Secondary objectives included overall tumor response rate (overall response equals complete response plus partial response) and overall survival.

RESULTS:

Of the 91 patients enrolled, 70 were evaluable for efficacy. Although no complete responses were observed, 7 patients had partial responses, for an overall response rate of 10% in the evaluable population. The median TTP for the evaluable population was 10 weeks, and the proportion of patients who were free of disease progression at 6 months was 23%. The median overall survival was 59.4 weeks for all patients enrolled. Common, drug‐related ≥ grade 3 adverse events (graded according to National Cancer Institute Common Toxicity Criteria, version 2) included diarrhea, vomiting, abdominal pain, and nausea.

CONCLUSIONS:

The combination of UFT and leucovorin administered orally in a 3‐times‐daily regimen was found to have modest activity. Grade 3 toxicities were manageable with appropriate dose adjustments in patients with metastatic breast cancer previously treated with anthracyclines and/or taxanes. Cancer 2010. © 2010 American Cancer Society.
Somatostatin interneurons delineate the inner part of the external plexiform layer in the mouse main olfactory bulb
Authors: Lepousez Gabriel , Csaba Zsolt , Bernard Véronique , Loudes Catherine , Videau Catherine , Lacombe Joelle , Epelbaum Jacques , Viollet Cécile
Published: January 2010

Neuropeptides play a major role in the modulation of information processing in neural networks. Somatostatin, one of the most concentrated neuropeptides in the brain, is found in many sensory systems including the olfactory pathway. However, its cellular distribution in the mouse main olfactory bulb (MOB) is yet to be characterized. Here we show that ≈95% of mouse bulbar somatostatin‐immunoreactive (SRIF‐ir) cells describe a homogeneous population of interneurons. These are restricted to the inner lamina of the external plexiform layer (iEPL) with dendritic field strictly confined to the region. iEPL SRIF‐ir neurons share some morphological features of Van Gehuchten short‐axon cells, and always express glutamic acid decarboxylase, calretinin, and vasoactive intestinal peptide. One‐half of SRIF‐ir neurons are parvalbumin‐ir, revealing an atypical neurochemical profile when compared to SRIF‐ir interneurons of other forebrain regions such as cortex or hippocampus. Somatostatin is also present in fibers and in a few sparse presumptive deep short‐axon cells in the granule cell layer (GCL), which were previously reported in other mammalian species. The spatial distribution of somatostatin interneurons in the MOB iEPL clearly outlines the region where lateral dendrites of mitral cells interact with GCL inhibitory interneurons through dendrodendritic reciprocal synapses. Symmetrical and asymmetrical synaptic contacts occur between SRIF‐ir dendrites and mitral cell dendrites. Such restricted localization of somatostatin interneurons and connectivity in the bulbar synaptic network strongly suggest that the peptide plays a functional role in the modulation of olfactory processing. J. Comp. Neurol. 518:1976–1994, 2010. © 2010 Wiley‐Liss, Inc.
Language‐related Cntnap2 gene is differentially expressed in sexually dimorphic song nuclei essential for vocal learning in songbirds
Authors: Panaitof S. Carmen , Abrahams Brett S. , Dong Hongmei , Geschwind Daniel H. , White Stephanie A.
Published: January 2010

Multiple studies, involving distinct clinical populations, implicate contactin associated protein‐like 2 (CNTNAP2) in aspects of language development and performance. While CNTNAP2 is broadly distributed in developing rodent brain, it shows a striking gradient of frontal cortical enrichment in developing human brain, consistent with a role in patterning circuits that subserve higher cognition and language. To test the hypothesis that CNTNAP2 may be important for learned vocal communication in additional species, we employed in situ hybridization to characterize transcript distribution in the zebra finch, an experimentally tractable songbird for which the neural substrate of this behavior is well established. Consistent with an important role in learned vocalization, Cntnap2 was enriched or diminished in key song control nuclei relative to adjacent brain tissue. Importantly, this punctuated expression was observed in males, but not females, in accord with the sexual dimorphism of neural circuitry and vocal learning in this species. Ongoing functional work will provide important insights into the relationship between Cntnap2 and vocal communication in songbirds and thereby clarify mechanisms at play in disorders of human cognition and language. J. Comp. Neurol. 518:1995–2018, 2010. © 2010 Wiley‐Liss, Inc.
Synaptic input of ON‐bipolar cells onto the dopaminergic neurons of the mouse retina
Authors: Contini Massimo , Lin Bin , Kobayashi Kazuto , Okano Hideyuki , Masland Richard H. , Raviola Elio
Published: January 2010

In the retina, dopamine fulfills a crucial role in neural adaptation to photopic illumination, but the pathway that carries cone signals to the dopaminergic amacrine (DA) cells was controversial. We identified the site of ON‐cone bipolar input onto DA cells in transgenic mice in which both types of catecholaminergic amacrine (CA) cells were labeled with green fluorescent protein or human placental alkaline phosphatase (PLAP). In confocal Z series of retinal whole mounts stained with antibodies to tyrosine hydroxylase (TH), DA cells gave rise to varicose processes that descended obliquely through the scleral half of the inner plexiform layer (IPL) and formed a loose, tangential plexus in the middle of this layer. Comparison with the distribution of the dendrites of type 2 CA cells and examination of neurobiotin‐injected DA cells proved that their vitreal processes were situated in stratum S3 of the IPL. Electron microscope demonstration of PLAP activity showed that bipolar cell endings in S3 established ribbon synapses onto a postsynaptic dyad in which one or both processes were labeled by a precipitate of lead phosphate and therefore belonged to DA cells. In places, the postsynaptic DA cell processes returned a reciprocal synapse onto the bipolar endings. Confocal images of sections stained with antibodies to TH, kinesin Kif3a, which labels synaptic ribbons, and glutamate or GABAA receptors, confirmed that ribbon‐containing endings made glutamatergic synapses onto DA cells processes in S3 and received from them GABAergic synapses. The presynaptic ON‐bipolar cells most likely belonged to the CB3 (type 5) variety. J. Comp. Neurol. 518:2035–2050, 2010. © 2010 Wiley‐Liss, Inc.
Progression of neuronal and synaptic remodeling in the rd10 mouse model of retinitis pigmentosa
Authors: Phillips M. Joseph , Otteson Deborah C. , Sherry David M.
Published: January 2010

The Pde6brd10 (rd10) mouse has a moderate rate of photoreceptor degeneration and serves as a valuable model for human autosomal recessive retinitis pigmentosa (RP). We evaluated the progression of neuronal remodeling of second‐ and third‐order retinal cells and their synaptic terminals in retinas from Pde6brd10 (rd10) mice at varying stages of degeneration ranging from postnatal day 30 (P30) to postnatal month 9.5 (PNM9.5) using immunolabeling for well‐known cell‐ and synapse‐specific markers. Following photoreceptor loss, changes occurred progressively from outer to inner retina. Horizontal cells and rod and cone bipolar cells underwent morphological remodeling that included loss of dendrites, cell body migration, and the sprouting of ectopic processes. Gliosis, characterized by translocation of Müller cell bodies to the outer retina and thickening of their processes, was evident by P30 and became more pronounced as degeneration progressed. Following rod degeneration, continued expression of VGluT1 in the outer retina was associated with survival and expression of synaptic proteins by nearby second‐order neurons. Rod bipolar cell terminals showed a progressive reduction in size and ectopic bipolar cell processes extended into the inner nuclear layer and ganglion cell layer by PNM3.5. Putative ectopic conventional synapses, likely arising from amacrine cells, were present in the inner nuclear layer by PNM9.5. Despite these changes, the laminar organization of bipolar and amacrine cells and the ON‐OFF organization in the inner plexiform layer was largely preserved. Surviving cone and bipolar cell terminals continued to express the appropriate cell‐specific presynaptic proteins needed for synaptic function up to PNM9.5. J. Comp. Neurol. 518:2071–2089, 2010. © 2010 Wiley‐Liss, Inc.
Connections of the auditory brainstem in a songbird, Taeniopygia guttata. II. Projections of nucleus angularis and nucleus laminaris to the superior olive and lateral lemniscal nuclei
Authors: Krützfeldt Nils O.E. , Logerot Priscilla , Kubke M. Fabiana , Wild J. Martin
Published: January 2010

Three nuclei of the lateral lemniscus are present in the zebra finch, ventral (LLV), intermediate (LLI), and dorsal (LLD). LLV is separate from the superior olive (OS): it lies closer to the spinal lemniscus and extends much further rostrally around the pontine periphery. LLI extends from a caudal position ventrolateral to the principal sensory trigeminal nucleus (LLIc) to a rostral position medial to the ventrolateral parabrachial nucleus (LLIr). LLD consists of posterior (LLDp) and anterior (LLDa) parts, which are largely coextensive rostrocaudally, although LLDa lies medial to LLDp. All nuclei are identifiable on the basis of cytochrome oxidase activity. The cochlear nucleus angularis (NA) and the third‐order nucleus laminaris (NL) project on OS predominantly ipsilaterally, on LLV and LLI predominantly contralaterally, and on LLD contralaterally only. The NA projections are heavier than those of NL and differ from them primarily in their terminations within LLD: NA projects to LLDp, whereas NL projects to LLDa. In this the projections are similar to those in the barn owl (Takahashi and Konishi [1988] J Comp Neurol 274:212–238), in which time and intensity pathways remain separate as far as the central nucleus of the inferior colliculus (MLd). In contrast, in the zebra finch, although NA and NL projections remain separate within LLD, the projections of LLDa and LLDp become intermixed within MLd (Wild et al., J Comp Neurol, this issue), consistent with the intermixing of the direct NA and NL projections to MLd (Krützfeldt et al., J Comp Neurol, this issue). J. Comp. Neurol. 518:2135–2148, 2010. © 2010 Wiley‐Liss, Inc.
Distribution and phenotype of Phox2a‐containing neurons in the adult sprague‐dawley rat
Authors: Card J. Patrick , Lois James , Sved Alan F.
Published: January 2010

Phox2a is a transcription factor that plays an essential role, with Phox2b, in the specification of the adrenergic and noradrenergic phenotype in developing brain. Localization of Phox2a in developing brainstem has demonstrated a high degree of correspondence between neurons expressing the transcription factor and those involved in the regulation of autonomic function. Although it is well established that the paralogous gene product Phox2b is widely expressed in adult brain, no study has mapped the distribution of Phox2a in the adult. The data reported here address that void. A well‐characterized rabbit polyclonal antiserum was used for immunohistochemical localization of the transcription factor in adult rats. Sections through the rostrocaudal extent of brain were processed for dual immunocytochemical localization of Phox2a and catecholamine enzymes. Adjacent sections were used for dual localization of Phox2a and NADPH diaphorase, a marker of nitric oxide‐containing neurons. The data demonstrate that Phox2a is present in all brainstem catecholamine neurons, in circumscribed populations of NADPH+ neurons, and in a subset of neurons that influences sympathetic and parasympathetic outflow. In addition, Phox2a+ neurons were observed within diencephalic and brainstem nuclei that regulate behavioral state. Considered with data demonstrating that Phox2a is part of the transcriptional complex that drives expression of dopamine‐β‐hydroxylase and can also up‐regulate expression of other genes, the data support the conclusion that Phox2a plays an important role in brainstem catecholamine neurotransmission and in the regulation of adaptive homeostatic functions in the adult nervous system. J. Comp. Neurol. 518:2202–2220, 2010. © 2010 Wiley‐Liss, Inc.
Antigenic compartmentation of the cerebellar cortex in the chicken (Gallus domesticus)
Authors: Marzban Hassan , Chung Seung‐Hyuk , Pezhouh Maryam Kherad , Feirabend Hans , Watanabe Masahiko , Voogd Jan , Hawkes Richard
Published: January 2010

The chick is a well‐understood developmental model of cerebellar pattern formation,but we know much less about the patterning of the adult chicken cerebellum. Therefore an expression study of two Purkinje cell stripe antigens—zebrin II/aldolase C and phospholipase Cβ4 (PLCβ4)—has been carried out in the adult chicken (Gallus domesticus). The mammalian cerebellar cortex is built around transverse expression domains (“transverse zones”), each of which is further subdivided into parasagittally oriented stripes. The results from the adult chicken reveal a similar pattern. Five distinct transverse domains were identified. In the anterior lobe a uniformly zebrin II‐immunopositive/PLCβ4‐immunonegative lingular zone (LZ; lobule I) and a striped anterior zone (AZ; lobules II–VIa) were distinguished. A central zone (CZ; ∼lobules VIa–VIIIa,b) and a posterior zone (PZ; ∼lobules VIIIa,b–IXc,d) were distinguished in the posterior lobe. Finally, the nodular zone (NZ; lobule X) is uniformly zebrin II‐immunoreactive and is innervated by vestibular mossy fibers. Lobule IXc,d is considered as a transitional region between the PZ and the NZ, because the vestibular mossy fiber projection extends into these lobules and because they receive optokinetic mossy and climbing fiber input. It is proposed that the zebrin II‐immunonegative P3‐ stripe corresponds to the lateral vermal B zone of the mammalian cerebellum and that the border between the avian homologs of the mammalian vermis and hemispheres is located immediately lateral to P3−. Thus, there seem to be transverse zones in chicken that are plausible homologs of those identified in mammals, together with an LZ that is characteristic of birds. J. Comp. Neurol. 518:2221–2239, 2010. © 2010 Wiley‐Liss, Inc.
Connections of the auditory brainstem in a Songbird, Taeniopygia guttata. I. Projections of nucleus angularis and nucleus laminaris to the auditory torus
Authors: Krützfeldt Nils O.E. , Logerot Priscilla , Kubke M. Fabiana , Wild J. Martin
Published: January 2010

Auditory information is important for social and reproductive behaviors in birds generally, but is crucial for oscine species (songbirds), in particular because in these species auditory feedback ensures the learning and accurate maintenance of song. While there is considerable information on the auditory projections through the forebrain of songbirds, there is no information available for projections through the brainstem. At the latter levels the prevalent model of auditory processing in birds derives from an auditory specialist, the barn owl, which uses time and intensity parameters to compute the location of sounds in space, but whether the auditory brainstem of songbirds is similarly functionally organized is unknown. To examine the songbird auditory brainstem we charted the projections of the cochlear nuclei angularis (NA) and magnocellularis (NM) and the third‐order nucleus laminaris (NL) in zebra finches using standard tract‐tracing techniques. As in other avian species, the projections of NM were found to be confined to NL, and NL and NA provided the ascending projections. Here we report on differential projections of NA and NL to the torus semicircularis, known in birds as nucleus mesencephalicus lateralis, pars dorsalis (MLd), and in mammals as the central nucleus of the inferior colliculus (ICc). Unlike the case in nonsongbirds, the projections of NA and NL to MLd in the zebra finch showed substantial overlap, in agreement with the projections of the cochlear nuclei to the ICc in mammals. This organization could suggest that the “what” of auditory stimuli is as important as “where.” J. Comp. Neurol. 518:2109–2134, 2010. © 2010 Wiley‐Liss, Inc.
Cellular configuration of single octopamine neurons in Drosophila
Authors: Busch Sebastian , Tanimoto Hiromu
Published: January 2010

Individual median octopamine neurons in the insect central nervous system serve as an excellent model system for comparative neuroanatomy of single identified cells. The median octopamine cluster of the subesophageal ganglion consists of defined sets of paired and unpaired interneurons, which supply the brain and subesophageal ganglion with extensive ramifications. The developmental program underlying the complex cellular network is unknown. Here we map the segmental location and developmental origins of individual octopamine neurons in the Drosophila subesophageal ganglion. We demonstrate that two sets of unpaired median neurons, located in the mandibular and maxillary segments, exhibit the same projection patterns in the brain. Furthermore, we show that the paired and unpaired neurons belong to distinct lineages. Interspecies comparison of median neurons revealed that many individual octopamine neurons in different species project to equivalent target regions. Such identified neurons with similar morphology can derive from distinct lineages in different species (i.e., paired and unpaired neurons). J. Comp. Neurol. 518:2355–2364, 2010. © 2010 Wiley‐Liss, Inc.
Dual labeling with a far red probe permits analysis of growth and oxidative stress in P. falciparum‐infected erythrocytes
Authors: Fu Ying , Tilley Leann , Kenny Shannon , Klonis Nectarios
Published: January 2010

The malaria parasite, Plasmodium falciparum, develops within human erythrocytes, consuming host hemoglobin to support its own growth. Reactive oxygen species (superoxide and hydrogen peroxide) are by‐products of hemoglobin digestion and are believed to exert significant oxidative stress on the parasite. We have characterized a cell permeant, far red fluorescent nucleic acid‐binding dye, SYTO 61, that can be used to distinguish between uninfected and infected erythrocytes in a flow cytometric format. The spectral properties of SYTO 61 make it suitable for use in combination with the fluorescent reactive oxygen species reporter 5‐(and‐6)‐chloromethyl‐2′,7′‐dichlorodihydro‐fluorescein diacetate acetyl ester. We have used this probe combination to measure oxidative stress in different stages of live P. falciparum. Low levels of the oxidized, fluorescent form of the reporter (2′,7′‐dichlorofluorescein, DCF) are detected in ring stage parasites; the DCF signal increases as the intraerythrocytic parasite matures into the trophozoite stage where active hemoglobin digestion occurs. Treatment of infected erythrocytes with the cysteine protease inhibitor, E‐64, which inhibits hemoglobin digestion, decreases the DCF signal. We show that E‐64 prevents schizont rupture but also causes delayed lethal effects when ring stage cultures are exposed to the drug. We also examined cultures of parasites in erythrocytes harboring 98% catalase inactivation and found no effect on growth and only a modest increase in DCF oxidation. © 2010 International Society for Advancement of Cytometry
Cytology of sclerosing epithelioid fibrosarcoma in pleural effusion
Authors: Tsuchido Keiko , Yamada Makoto , Satou Tamami , Otsuki Yoshiro , Shimizu Shin‐ichi , Kobayashi Hiroshi
Published: January 2010

We report a case of sclerosing epithelioid fibrosarcoma focusing on its cytological features in pleural effusion. A 32‐year‐old man had noticed a tumor in his left buttock 5 years earlier but had not sought treatment because the tumor had been painless. He visited our hospital because the tumor had gradually increased in size. The resected tumor was 12 × 8 × 6 cm in size and had a delineated margin. The histological diagnosis was sclerosing epithelioid fibrosarcoma with a negative surgical margin. Multiple tumor nodules were recognized in both lungs 9 months after the initial surgery, and an excisional biopsy was performed. A histological examination revealed a metastasis of sclerosing epithelioid fibrosarcoma, and chemotherapy was initiated. Pleural disseminations were detected 4 years after the chemotherapy, and the pleural effusion was sampled for cytological examination. The cytological examination revealed several medium‐sized cell clusters with moderate overcrowding and an epithelioid cell arrangement; numerous histiocytes and lymphocytes and a small amount of mesothelial cells were observed in the background. The nuclei were pleomorphic with oval, spindle, or cleaved shapes and occasional multinucleation; they were located eccentrically in the cytoplasm and exhibited uniformly fine granular chromatin, a thin nuclear membrane, and several small nucleoli. The above cytological features, coupled with the clinical findings, enabled a diagnosis of sclerosing epithelioid fibrosarcoma. To our knowledge, this is the first cytological description of sclerosing epithelioid fibrosarcoma. Diagn. Cytopathol. 2010;38:748–753. © 2010 Wiley‐Liss, Inc.
Role of fine needle aspiration cytology in diagnosis of filarial infestation
Authors: Kumar Bipin , Karki Smriti , Yadava Sanjay Kumar
Published: January 2010

Filariasis is a tropical disease transmitted by the Culex mosquitoes. The diagnosis of it is conventionally made by demonstrating microfilariae in the peripheral blood smear. However; microfilariae and adult filarial worm have been incidentally detected in fine needle aspirates of various lesions in clinically unsuspected cases. The cases of filariasis diagnosed by fine needle aspiration cytology (FNAC) were retrieved from the archives of the Cytopathology laboratory between the periods of January 1998 to February 2009. Both Papanicolaou‐ and May–Grunwald–Giemsa‐stained smears were available in all the cases. A total of 26 diagnosed cases of filariasis were found, of which 19 were related to funiculo‐epididymitis, four presented with breast lump, and three cases with lymphadenopathy. Smears revealed fragments of adult worm in 12 cases including 10 gravid female worm containing eggs and microfilariae and two male adult worm; whereas in remaining 14 cases only microfilariae or eggs were seen. Unfertilized eggs were seen in three cases and fertilized eggs were seen in five cases. Tissue response in the form of eosinophils in 16 cases, acute inflammatory exudate in five cases, macrophages in 22 cases, epitheloid cell granulomas in five cases, giant cells in four cases, lymphocytes in 10 cases, and plasma cells in three cases were seen. Adherence of polymorphonuclear leukocytes, eosinophils, and epithelioid cells were observed in four cases. On conclusion, filaria may affect the epididymis, spermatic cord, breast, and lymph node, and the accurate diagnosis can be easily and conveniently achieved by FNAC without any requirement of biopsy. Diagn. Cytopathol. 2011;39:8–12. © 2010 Wiley‐Liss, Inc.
Fluorescein‐Functionalized Silica Nanoparticles as a Selective Fluorogenic Chemosensor for Cu2+ in Living Cells
Authors: Seo Sungmin , Lee Hye Young , Park Minsung , Lim Jung Mi , Kang Dongmin , Yoon Juyoung , Jung Jong Hwa
Published: January 2010

Fluorescein‐functionalized silica nanoparticles (1) were prepared by sol–gel reaction, and their optical sensing abilities were studied towards finding a new type of synthetic fluorogenic chemosensor for imaging Cu2+ ions in living cells. Interestingly, upon addition of Cu2+ in a H2O suspension of 1 at pH 7.4, 1 displays large chelation‐enhanced quenching (CHEQ) effects with Cu2+. With the exception of Cu2+, no significant fluorescence intensity changes were observed in the experiments with the other metal ions. These findings confirm that 1 can be useful as a fluorogenic‐sensing material for the selective detection of Cu2+ in the presence of other metal ions. This is a rare example of chromogenic sensing of a specific metal ion by functional inorganic nanomaterials. The emission change observed for chemosensor 1 in the presence of Cu2+ is reversible by the addition of EDTA. Furthermore, the fluorescein‐functionalized silica nanoparticles act as a new type of synthetic fluorogenic chemosensor for imaging Cu2+ ions in living cells.
Regioselective Arylations of α‐Amido Sulfones with Electron‐Rich Arenes through Friedel–Crafts Alkylations Catalyzed by Ferric Chloride Hexahydrate: Synthesis of Unsymmetrical and Bis‐Symmetrical Triarylmethanes
Authors: Thirupathi Ponnaboina , Kim Sung Soo
Published: January 2010

Ferric chloride hexahydrate is a highly efficient catalyst for the regioselective arylation of α‐amido sulfones. The products undergo further Friedel–Crafts alkylations with heteroaromatic or electron‐rich arenes to afford unsymmetrical or bis‐symmetrical triarylmethanes.
Palladium‐Catalyzed Alkenylation of 1,2,3‐Trizoles with Terminal Conjugated Alkenes by Direct C–H Bond Functionalization
Authors: Jiang Huanfeng , Feng Zhenning , Wang Azhong , Liu Xiaohang , Chen Zhengwang
Published: January 2010

A palladium‐catalyzed alkenylation of 1,2,3‐triazoles with terminal conjugated alkenes by direct C–H functionalization has been developed in the presence of Cu(OAc)2 and dioxygen. A variety of terminal alkenes such as acrylates and styrenes can perform the direct oxidative coupling reactions with 1,2,3‐triazoles to afford the corresponding alkenylated products in 30–90 % yield.
Carbon nanotubes induce oxidative DNA damage in RAW 264.7 cells
Authors: Migliore Lucia , Saracino Doriana , Bonelli Alessia , Colognato Renato , D'Errico Maria R. , Magrini Andrea , Bergamaschi Antonio , Bergamaschi Enrico
Published: January 2010

The induction of DNA and chromosome damage following in vitro exposure to carbon nanotubes (CNT) was assessed on the murine macrophage cell line RAW 264.7 by means of the micronucleus (MN) and the comet assays. Exposures to two CNT preparations (single‐walled CNT (SWCNT > 90%) and multiwalled CNT (MWCNT > 90%) were performed in increasing mass concentrations (0.01–100 μg/ml). The frequency of micronuclei was significantly increased in cells treated with SWCNT (at doses above 0.1 μg/ml), whereas MWCNT had the same effect at higher concentrations (1 μg/ml) (P < 0.05). The results of the comet assay revealed that the effects of treatment with SWCNT were detectable at all concentrations tested (1–100 μg/ml); oxidized purines increased significantly, whereas pyrimidines showed a significant increase (P < 0.001) only at the highest concentration (100 μg/ml). In cells treated with MWCNT, an increase in DNA migration due to the oxidative damage to purines was observed at a concentration of 1 and 10 μg/ml, whereas pyrimidines showed a significant increase only at the highest mass concentration tested. However, both SWCNT and MWCNT induced a statistically significant cytotoxic effect at the highest concentrations tested (P < 0.001). These findings suggest that both the MN and comet assays can reliably detect small amount of damaged DNA at both chromosome and nuclear levels in RAW 264.7 cells. Moreover, the modified version of the comet assay allows the specific detection of the induction of oxidative damage to DNA, which may be the underlying mechanism involved in the CNT‐associated genotoxicity. Environ. Mol. Mutagen., 2010. © 2010 Wiley‐Liss, Inc.
Involvement of gp130‐associated cytokine signaling in Müller cell activation following optic nerve lesion
Authors: Kirsch Matthias , Trautmann Nikolaus , Ernst Matthias , Hofmann Hans‐Dieter
Published: January 2010

Ciliary neurotrophic factor (CNTF) and the related cytokine leukemia inhibitory factor (LIF) have been implicated in regulating astrogliosis following CNS lesions. Application of the factors activates astrocytes in vivo and in vitro, and their expression as well as their receptors is upregulated after brain injury. Here, we investigated their function by studying Müller cell activation induced by optic nerve crush in CNTF‐ and LIF‐deficient mice, and in animals with deficiencies in cytokine signaling pathways. In the retina of CNTF–/– mice, basal GFAP expression was reduced, but unexpectedly, injury‐induced upregulation in activated Müller cells was increased during the first 3 days after lesion as compared to wild‐type animals and this corresponded with higher phosphorylation level of STAT3, an indicator of cytokine signaling. The observation that LIF expression was strongly upregulated in CNTF–/– mice but not in wild‐type animals following optic nerve lesion provided a possible explanation. In fact, additional ablation of the LIF gene in CNTF/LIF double knockout mice almost completely abolished early lesion‐induced GFAP upregulation in Müller cells and STAT3 phosphorylation. Early Müller cell activation was also eliminated in LIF–/– mice, despite normal CNTF levels, as well as in mutants deficient in gp130/JAK/STAT signaling and in conditional STAT3 knockout mice. Our results demonstrate that LIF signaling via the gp130/JAK/STAT3 pathway is required for the initiation of the astrogliosis‐like reaction of retinal Müller cells after optic nerve injury. A potential role of CNTF was possibly masked by a compensatory increase in LIF signaling in the absence of CNTF. © 2010 Wiley‐Liss, Inc.
NOD2 mediates inflammatory responses of primary murine glia to Streptococcus pneumoniae
Authors: Liu Xinjie , Chauhan Vinita S. , Young Amy B. , Marriott Ian
Published: January 2010

It is now widely accepted that resident central nervous system (CNS) cells such as microglia and astrocytes initiate and/or augment inflammation following trauma or infection. However, the mechanisms by which glial cells perceive microbial challenges are only now becoming apparent. We have recently demonstrated that microglia and astrocytes constitutively express nucleotide‐binding oligomerization domain‐2 (NOD2), a member of the novel nucleotide‐binding domain leucine‐rich repeat region‐containing family of proteins (NLR) that functions as an intracellular receptor for a minimal motif present in all bacterial peptidoglycans. Furthermore, we have shown that this NLR is essential for glial responses to gram‐negative pathogens and in vivo CNS inflammation elicited by these organisms. In the present study, we have established that intact Streptococcus pneumoniae, the major causative agent for gram‐positive bacterial meningitis in adults, is a potent stimulus for the activation of the pivotal inflammatory transcription factor NF‐kB and production of inflammatory cytokines in primary murine microglia and astrocytes. We demonstrate that NOD2 is essential for the maximal responses of these cells to intact S. pneumoniae but not cellular lysates. Finally, we have shown that this cytosolic pattern recognition receptor is required for the elevated inflammatory mediator levels, astrogliosis, and demyelination, following in vivo administration of this gram‐positive CNS pathogen. As such, we suggest that NOD2 plays a critical role in the establishment of the lethal inflammation associated with streptococcal meningitis. © 2010 Wiley‐Liss, Inc.
A Parametric Empirical Bayesian framework for fMRI‐constrained MEG/EEG source reconstruction
Authors: Henson Richard N. , Flandin Guillaume , Friston Karl J. , Mattout Jérémie
Published: January 2010

We describe an asymmetric approach to fMRI and MEG/EEG fusion in which fMRI data are treated as empirical priors on electromagnetic sources, such that their influence depends on the MEG/EEG data, by virtue of maximizing the model evidence. This is important if the causes of the MEG/EEG signals differ from those of the fMRI signal. Furthermore, each suprathreshold fMRI cluster is treated as a separate prior, which is important if fMRI data reflect neural activity arising at different times within the EEG/MEG data. We present methodological considerations when mapping from a 3D fMRI Statistical Parametric Map to a 2D cortical surface and thence to the covariance components used within our Parametric Empirical Bayesian framework. Our previous introduction of a canonical (inverse‐normalized) cortical mesh also allows deployment of fMRI priors that live in a template space; for example, from a group analysis of different individuals. We evaluate the ensuing scheme with MEG and EEG data recorded simultaneously from 12 participants, using the same face‐processing paradigm under which independent fMRI data were obtained. Because the fMRI priors become part of the generative model, we use the model evidence to compare (i) multiple versus single, (ii) valid versus invalid, (iii) binary versus continuous, and (iv) variance versus covariance fMRI priors. For these data, multiple, valid, binary, and variance fMRI priors proved best for a standard Minimum Norm inversion. Interestingly, however, inversion using Multiple Sparse Priors benefited little from additional fMRI priors, suggesting that they already provide a sufficiently flexible generative model. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.
Clinicopathologic and therapeutic risk factors for perioperative complications and prolonged hospital stay in free flap reconstruction of the head and neck
Authors: Patel Rajan S. , McCluskey Stuart A. , Goldstein David P. , Minkovich Leonid , Irish Jonathan C. , Brown Dale H. , Gullane Patrick J. , Lipa Joan E. , Gilbert Ralph W.
Published: January 2010

Background

We aimed to determine predictors of morbidity in patients undergoing microvascular free flap reconstruction of the head and neck.

Methods

We prospectively evaluated 796 cases between 1999 and 2007 using univariate and multivariate analysis to determine predictors of morbidity and prolonged hospital stay.

Results

Two hundred thirty‐nine patients (30%) developed major complications. Age, body mass index (BMI), American Society of Anesthesiology (ASA) score, Kaplan Feinstein comorbidity index (KFI) score, preoperative hemoglobin, and tracheostomy were independent predictors of major complication. Predictors of prolonged hospital stay included age, recent weight loss, alcohol excess, ASA, KFI, preoperative hemoglobin, mucosal surgery, anesthesia duration, and crystalloid replacement volume.

Conclusion

Several variables are associated with an increased risk of development of major complications following free flap reconstruction of the head and neck. Although many of these variables are irreversible, they aid risk stratification of patients undergoing free flap reconstruction, and assist clinicians in making treatment decisions, consenting, and providing patients with realistic expectations regarding their perioperative course. © 2010 Wiley Periodicals, Inc. Head Neck, 2010
Impact of positive frozen section microscopic tumor cut‐through revised to negative on oral carcinoma control and survival rates
Authors: Patel Rajan S. , Goldstein David P. , Guillemaud Jennifer , Bruch Guillem Andreu , Brown Dale , Gilbert Ralph W. , Gullane Patrick J. , Higgins Kevin M. , Irish Jonathan , Enepekides Danny J.
Published: January 2010

Background

The objective of the study was to evaluate the prognostic and therapeutic implications of an initial positive frozen section margin that was revised until negative (microscopic tumor cut‐through), and to analyze the influence of microscopic margin status on oral carcinoma control.

Methods

The approach in our investigation was through a retrospective review of patients treated with primary surgery, with frozen section margin control in oral carcinoma. Inclusion criteria included availability of frozen and permanent section histology reports of resection margins and negative final resection margins.

Results

Of 547 patients studied, 175 received adjuvant radiation. Local and regional control and disease‐specific survival rates were 81.6%, 78.4%, and 76.3%, respectively. Tumor cut‐through and pathologic nodal (pN) stage had an independently adverse effect on local control. Tumor cut‐through adversely affected cancer control and survival, but this effect diminished significantly in the absence of regional disease.

Conclusions

Microscopic tumor cut‐through revised to negative margins is a powerful prognosticator that is observed only when regional disease is also present. The value of adjuvant therapeutic regimens is questionable in patients with microscopic tumor cut‐through, revised to negative margins, and with no regional disease. © 2010 Wiley Periodicals, Inc. Head Neck, 2010
Expression of placenta growth factor: An independent factor for prediction of progression and prognosis of oral cancer
Authors: Cheng Shih‐Jung , Lee Jang‐Jaer , Kok Sang‐Heng , Chou Chia‐Hsuan , Chang Hao‐Hueng , Ling Chiang Meng , Chen Hsin‐Ming , Kuo Mark Yen‐Ping , Chiang Chun‐Pin
Published: January 2010

Background.

Expression of placenta growth factor (PlGF) is found to correlate with the progression and prognosis of several human cancers.

Methods.

This study used an immunohistochemical technique to examine the expression of PlGF in 100 specimens of oral squamous cell carcinoma (OSCC).

Results.

We found that the higher mean PlGF labeling index was significantly associated with OSCCs with positive lymph node metastasis (p = .014) or with more advanced clinical stages (p = .016). Positive lymph node metastasis (p = .008) and PlGF labeling index >40% (p = .010) were identified as independent unfavorable prognosis factors by multivariate analyses with Cox regression model. Moreover, a Kaplan–Meier curve showed that OSCC patients with a PlGF labeling index >40% had a significantly poorer cumulative survival than those with a PlGF labeling index ≤40% (log‐rank test, p = .003).

Conclusions.

The PlGF labeling index can predict the progression and prognosis of OSCCs in Taiwan. © 2010 Wiley Periodicals, Inc. Head Neck, 2010
Hypopharyngeal perforation during endoscopic ultrasound treated by primary repair
Authors: Sharma Neil , Jindal Mudit , Mahon Brinder , Pracy Paul
Published: January 2010

Background.

An endoscopic ultrasound scan is a common procedure used to diagnose conditions of the upper gastrointestinal tract. We present a case of hypopharyngeal perforation complicating endoscopic ultrasound scan treated with primary surgical repair.

Methods and Results.

A 62‐year‐old woman underwent an endoscopic ultrasound scan for investigation of a pancreatic lesion. A high esophageal perforation occurred during the procedure. She underwent emergency repair of this perforation via an external approach. Unfortunately her recovery was complicated by a pleural effusion which required a chest drain. She made a complete recovery, which was confirmed with a barium swallow.

Discussion.

Upper esophageal perforation is a rare complication of an endoscopic ultrasound scan and, to our knowledge, there have been no reported cases of hypopharyngeal perforation. The risk factors, incidence, and management of perforations are reviewed. Early recognition of hypopharyngeal perforation is important and, in selected cases, immediate repair of the defect can lead to a good result. © 2010 Wiley Periodicals, Inc. Head Neck, 2011
Two New Phenylpropanoid Glycosides from the Leaves and Flowers of Erica arborea
Authors: Demirkiran Ozlem , Topçu Gülaçtı , Bahadori Fatemeh , Ay Mehmet , Nazemiyeh Hossein , Choudhary Iqbal
Published: January 2010

Two new phenylpropanoid glucosides, 1,2‐erythro‐1‐(3,4,5‐trimethoxyphenyl)‐2‐(β‐D‐glucopyranosyloxy)propan‐1,3‐diol (1) and 7,8‐threo‐2′,8‐epoxysyringylglycerol‐7‐O‐α‐D‐glucopyranoside (ericarboside; 2) have been isolated together with four known compounds 2′,7‐epoxysyringylglycerol‐8‐O‐β‐D‐glucopyranoside (ficuscarpanoside B; 3), benzylrutinoside (hydrangeifolin; 4), phenethylrutinoside (5), and caffeic acid from the BuOH soluble part of the MeOH extract of the leaves and flowers of E. arborea L. Final purification of the compounds was achieved on a reversed‐phase HPLC. Their structures have been elucidated by extensive 1D‐ and 2D‐NMR, and mass spectroscopic techniques.
Sesquiterpene Lactones from Daucus glaber
Authors: Sallam Amal A. , Hitotsuyanagi Yukio , Mansour El‐Sayed S. , Ahmed Atallah F. , Gedara Sahar , Fukaya Haruhiko , Takeya Koichi
Published: January 2010

Six new sesquiterpene lactone esters, daucoguaianolactones A–F (1–6), and one new sesquiterpene lactone, daucoeudesmanolactone A (7) were isolated from the leaves and stems of Daucus glaber (Forssk.) Thell., along with the known sesquiterpene lactones talasins A and B and badkhysin. The structures of 1–6 were established on the basis of extensive 1D‐ and 2D‐NMR spectroscopic studies and that of 7 by X‐ray crystallography. Compounds 4, 7, and talasins A and B showed moderate cytotoxicity against P‐388 leukemia cells.
Two New Alkaloids from Stemona tuberosa
Authors: Zhong Ying , Gao Ying , Guo Qiu‐Ping , Li Wei‐Min
Published: January 2010

Two new alkaloids, named tuberostemoninol A (1) and tuberostemoninol B (2), along with the known compounds tuberostemoninol (3) and bisdehydroneotuberostemonine (4), were isolated from Stemona tuberosa Lour. The structures were elucidated by means of spectroscopic analyses, including 1D‐ and 2D‐NMR experiments. The four alkaloids 1–4 were analyzed by on‐line high‐performance liquid chromatography/electrospray‐ionization mass spectrometry (HPLC/ESI‐MS), and their fragmentation pathways were found to be similar. Compounds 1, 2, and 3 are isomers with the same molecular mass but which eluted at different retention times.
Stereoselective Total Synthesis of (11β)‐11‐Methoxycurvularin
Authors: Rajesh Karuturi , Suresh Vangaru , Selvam Jondoss Jon Paul , Babu Dokuburra Chanti , Venkateswarlu Yenamandra
Published: January 2010

A simple and highly efficient stereoselective total synthesis of (11β)‐11‐methoxycurvularin (5), a polyketide natural product, was achieved. The synthesis commenced with a Cu‐mediated regioselective opening of (2S)‐2‐methyloxirane (6) and comprised a Keck asymmetric allylation and intramolecular Friedel–Crafts acylation as key steps (Scheme 2).
Secoiridoid Constituents from the Fruits of Ligustrum lucidum
Authors: Yang Nian‐Yun , Xu Xiao‐Hua , Ren Dong‐Chun , Duan Jin‐Ao , Xie Ning , Tian Li‐Juan , Qian Shi‐Hui
Published: January 2010

Four new secoiridiod glucosides, p‐hydroxyphenethyl 7‐β‐D‐glucosideelenolic acid ester (1), 6′‐elenolylnicotiflorine (2), 6′′′‐acetylnicotiflorine (3), and oleoside 7‐ethyl 11‐methyl ester (4), as well as six known glucosides, nuezhenide (5), Gl‐3 (6), nicotiflorine (7), isonuezhenide (8), neonuezhenide (9), and oleoside 11‐methyl ester (10) were isolated from the fruits of Ligustrum lucidum. Their structures were elucidated by spectroscopic methods. Compound 4 was an artifact produced during extraction.
Conformational Studies of (±)‐11,12‐Didehydro‐11‐deoxycorynoline and (+)‐11,13‐Didehydro‐11‐deoxychelidonine, Hexahydrobenzo[c]phenanthridine‐Type Alkaloid Derivatives, by X‐Ray Crystal Structure and NMR Analyses
Authors: Kamigauchi Miyoko , Maekawa Yukiko , Tode Chisato , In Yasuko , Ishida Toshimasa
Published: January 2010

The X‐ray crystal analyses of the two 11‐deoxy‐didehydrohexahydrobenzo[c]phenanthridine‐type alkaloid derivatives 3 and 4, derived from (±)‐corynoline (1) and (+)‐chelidonine (2), established their structures as (±)‐(5bRS,12bRS)‐5b,12b,13,14‐tetrahydro‐5b,13‐dimethyl[1,3]benzodioxolo[5,6‐c]‐1,3‐dioxolo[4,5‐i]phenanthridine (3) and (+)‐rel‐(12bR)‐7,12b,13,14‐tetrahydro‐13‐methyl[1,3]benzodioxolo[5,6‐c]‐1,3‐dioxolo[4,5‐i]phenanthridine (4). The conformations of 3 and 4 in CDCl3 were determined on the basis of 1H‐ and 13C‐NMR spectroscopy.
Catalytic Performance of Ruthenium‐Supported Ionic‐Liquid Catalysts in Sustainable Synthesis of Macrocyclic Lactones
Authors: Hagiwara Hisahiro , Nakamura Tomomi , Okunaka Naotaro , Hoshi Takashi , Suzuki Toshio
Published: January 2010

Thirteen‐ to eighteen‐membered lactones were synthesized by ring‐closing olefin‐metathesis reactions of bis‐olefins with heterogeneous Grubbs‐supported ionic‐liquid catalysts (SILCs), in which homogeneous Grubbs catalysts were confined in pores of alumina with the aid of an ionic liquid. The Grubbs‐SILCs exhibited higher catalytic performance than their homogeneous counterparts and could be repeatedly recovered by simple filtration and re‐used several times.
Fibromyalgia—pathways and neurotransmitters
Authors: Stahl Stephen M.
Published: January 2010

Fibromyalgia is a syndrome of widespread chronic pain associated with sleep disorders, depressed mood, cognitive impairment and fatigue. Its etiology and pharmacopathology are poorly understood but it is thought to result from a dysfunction of central pain processing mechanisms leading to generalised pain sensitisation. Pain perception is the result of a bidirectional process of ascending and descending pathways. Nociceptive input from peripheral afferent neurons is sent via the dorsal horn of the spinal cord to the higher brain centres involved in pain perception. Some descending inhibitory projections to the spinal cord attenuate the nociceptive effects. Numerous neurotransmitters including serotonin, dopamine, noradrenaline and substance P are involved in these processes. In other neuronal pathways in the brain, the same neurotransmitters are involved in mood control, sleep regulation and cognitive function providing a neurochemical substrate for the wide range of symptoms seen in fibromyalgia. Attenuation of neuronal hyperactivity through ligands acting at the α2‐δ subunits of voltage‐dependent calcium channels and increased inhibitory activity of the descending pathways by inhibition of serotonin and noradrenaline reuptake are two mechanisms that are currently exploited by new medication for the treatment of fibromyalgia. Copyright © 2009 John Wiley & Sons, Ltd.