bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term durable benefit after whole lung lavage in pulmonary alveolar proteinosis
Authors: Beccaria M. , Luisetti M. , Rodi G. , Corsico A. , Zoia M.C. , Colato S. , Pochetti P. , Braschi A. , Pozzi E. , Cerveri I.
Published: March 2004

Whole lung lavage (WLL) is still the gold-standard therapy for pulmonary alveolar proteinosis (PAP). The few studies on the duration of the effect of WLL, belonging to a rather remote period, show significant but transient benefits.

In 21 patients with idiopathic PAP, the duration of any benefit and, in 16 of them, the time course of lung function improvement (at baseline, 1 week, 6 months, 1 yr and then every 2 yrs after WLL) were evaluated. The present WLL technique takes longer, is invasively monitored and partially modified with respect to past techniques.

More than 70% of patients remained free from recurrent PAP at 7 yrs. The bulk of the improvement in spirometric results was almost completely gained in the immediate post‐WLL period due to the efficient clearance of the alveoli. At a median of 5 yrs, recovery of diffusing capacity of the lung for carbon monoxide was incomplete (75±19% of the predicted value) and there were residual gas exchange abnormalities (alveolar to arterial oxygen tension difference 3.6±1.5 kPa (27±11 mmHg)) and exercise limitation, probably explained by engorgement of lymphatic vessels.

In conclusion, whole lung lavage for idiopathic pulmonary alveolar proteinosis is currently a safe procedure in an experienced setting, and provides long-lasting benefits in the majority of patients.
Impact of Src Homology 2-Containing Inositol 5′-Phosphatase 2 on the Regulation of Insulin Signaling Leading to Protein Synthesis in 3T3-L1 Adipocytes Cultured with Excess Amino Acids
Authors: Murakami Shihou , Sasaoka Toshiyasu , Wada Tsutomu , Fukui Kazuhito , Nagira Kiyofumi , Ishihara Hajime , Usui Isao , Kobayashi Masashi
Published: March 2004

Src homology 2-containing inositol 5′-phosphatase 2 (SHIP2) possesses 5′-phosphatase activity to specifically hydrolyze the phosphatidylinositol 3-kinase product PI(3,4,5)P3 in the regulation of insulin signaling. In the present study, we examined the impact of SHIP2 on the regulation of insulin signaling leading to protein synthesis in 3T3-L1 adipocytes cultured with standard and excess concentrations of amino acids. Insulin-induced translocation of PDK1 to the plasma membrane, phosphorylation of Akt and p70S6-kinase and ribosomal protein S6, increase in the amount of 4E-BP1 γ-form, association of eIF4E with eIF4G, and protein synthesis were decreased by overexpression of wild-type SHIP2 by adenovirus-mediated gene transfer. The effect of SHIP2 overexpression on the regulation of insulin-induced phosphorylation of Akt and p70S6-kinase was somewhat augmented by the incubation with 5-fold excess concentrations of amino acids for 30 min. In contrast, the impact of SHIP2 expression was diminished in insulin-induced phosphorylation of p70S6-kinase and S6, but not of Akt, after the incubation for 16 h. Interestingly, incubation with the excess concentrations of amino acids for 30 min induced activation of phosphatidylinositol 3-kinase and phosphorylation of Akt, whereas phosphorylation of p70S6-kinase and S6 was decreased. Furthermore, although the exposure for longer time periods up to 24 h did not elicit phosphorylation of Akt, it markedly induced phosphorylation of p70S6-kinase and S6. These results indicate that SHIP2 plays an important role in the negative regulation of insulin signaling for the protein synthesis and that the impact of SHIP2 is altered, dependent on the acute or chronic exposure of excess concentrations of amino acids in culture.
Molecular Mechanisms of the Effects of Low Concentrations of Taxol in Anaplastic Thyroid Cancer Cells
Authors: Pushkarev V. M. , Starenki D. V. , Saenko V. A. , Namba H. , Kurebayashi J. , Tronko M. D. , Yamashita S.
Published: March 2004

Understanding the detailed mechanisms of a chemotherapeutic agent action on cancer cells is essential for planning the clinical applications because drug effects are often tissue and cell type specific. This study set out to elucidate the molecular pathways of Taxol effects in human anaplastic thyroid cancer cells using as an experimental model four cell lines, ARO, KTC-2, KTC-3 (anaplastic thyroid cancer), and FRO (undifferentiated follicular cancer), and primary thyrocytes. All cell lines were sensitive to Taxol, although to different extent. In primary thyrocytes the drug displayed substantially lower cytotoxicity. In thyroid cancer cells, Taxol-induced changes characteristic to apoptosis such as poly (ADP-ribose) polymerase and procaspase cleavage and alteration of membrane asymmetry only within a narrow concentration range, from 6 to 50 nm. At higher concentration, other form(s) of cell death perhaps associated with mitochondrial collapse was observed. Low doses of Taxol enhanced Bcl2 phosphorylation and led to its degradation observed on the background of a sustained or increasing Bax level and accumulation of survivin and X-chromosome-linked inhibitor of apoptosis. c-jun-NH2 terminal kinase activation was essential for the apoptosis in anaplastic thyroid cancer cells, whereas Raf/MAPK kinase/ERK and phosphatidylinositol-3-OH kinase/Akt were likely to comprise main survival mechanisms. Our results suggest an importance of cautious interpreting of biological effects of Taxol in laboratory studies and for determining optimal doses of Taxol to achieve the desired therapeutic effect in anaplastic thyroid cancers.
The Low-Density Lipoprotein Receptor Is Regulated by Estrogen and Forms a Functional Complex with the Estrogen-Regulated Protein Ezrin in Pituitary GH3 Somatolactotropes
Authors: Smith Perry M. , Cowan Ann , White Bruce A.
Published: March 2004

Estrogen regulates the function, growth, and proliferation of lactotropes in the pituitary. We report here that low-density lipoprotein (LDL) receptor (LDLR) gene expression and LDL uptake are strongly up-regulated by estrogen in pituitary somatolactotropic GH3 cells. The uptake of LDL was significantly inhibited by the F-actin-severing drug, swinholide A, indicating that LDL uptake is dependent on the integrity of the cortical actin cytoskeleton in GH3 cells. We examined whether the estrogen-inducible cytoskeletal linker protein, ezrin, interacts with the LDLR. The LDLR coimmunoprecipitated with ezrin, and fluorescently labeled LDL bound to regions of the cell membrane that colocalized with the active, phosphorylated form of ezrin (phosphoezrin). Evidence for a functional interaction between ezrin and the LDLR was obtained by transient transfection experiments using ezrin-green fluorescent protein (GFP) expression constructs. We observed that transient transfection of GH3 cells with an ezrin N terminus-GFP dominant-negative construct prevented the uptake of LDL particles, whereas expression of GFP alone or an ezrin C terminus-GFP construct had no effect on LDL uptake. Transfection with the ezrin N terminus dominant- negative construct had no effect on the endocytosis of transferrin. Thus, estrogen stimulates the expression of ezrin and the LDLR in GH3 cells, which interact physically and functionally to facilitate the endocytosis of LDL. We propose that the up-regulation and interaction of ezrin and the LDLR serves to augment the delivery of cholesterol and other lipids in support of the hypertrophic and proliferative response of cells to estrogen.
Cellular mechanisms of direct-current electric field effects: galvanotaxis and metastatic disease
Authors: Mycielska Maria E. , Djamgoz Mustafa B. A.
Published: March 2004

Endogenous direct-current electric fields (dcEFs) occur in vivo in the form of epithelial transcellular potentials or neuronal field potentials, and a variety of cells respond to dcEFs in vitro by directional movement. This is termed galvanotaxis. The passive influx of Ca2+ on the anodal side should increase the local intracellular Ca2+ concentration, whereas passive efflux and/or intracellular redistribution decrease the local intracellular Ca2+ concentration on the cathodal side. These changes could give rise to `push-pull' effects, causing net movement of cells towards the cathode. However, such effects would be complicated in cells that possess voltage-gated Ca2+ channels and/or intracellular Ca2+ stores. Moreover, voltage-gated Na+ channels, protein kinases, growth factors, surface charge and electrophoresis of proteins have been found to be involved in galvanotaxis. Galvanotactic mechanisms might operate in both the short term (seconds to minutes) and the long term (minutes to hours), and recent work has shown that they might be involved in metastatic disease. The galvanotactic responses of strongly metastatic prostate and breast cancer cells are much more prominent, and the cells move in the opposite direction compared with corresponding weakly metastatic cells. This could have important implications for the metastatic process and has clinical implications. Galvanotaxis could thus play a significant role in both cellular physiology and pathophysiology.
Preparative Synthesis of the Key Intermediate, (4R,5R)-3-Benzyloxymethyl-4,5-isopropylidenedioxycyclopent-2-enone for Carbocyclic Nucleosides
Authors: Moon Hyung Ryong , Choi Won Jun , Kim Hea Ok , Jeong Lak Shin
Published: March 2004

(4R,5R)-3-Benzyloxymethyl-4,5-isopropylidenedioxycyclopent-2-enone (1), a versatile intermediate for the synthesis of carbocyclic nucleosides was synthesized from d-ribose in 10 steps and 26% overall yield.
A Modified Thermodynamically Controlled Deracemization of 2-Allylcyclohexanone and Its Application to Asymmetric Synthesis of (R)-(−)-Epilachnene
Authors: Kaku Hiroto , Okamoto Natsuko , Nakamaru Aya , Tsunoda Tetsuto
Published: March 2004

The efficiency of thermodynamically controlled deracemization was influenced considerably by the solvent used. Based on this finding, an improved method was developed, by which 2-allylcyclohexanone was converted to the R-isomer of 93% ee in 72% yield. As an application of the method, (R)-(−)-epilachnene, an antipode of the defensive droplets from the Mexican bean beetle, Epilachna varivestis, was synthesized in short steps.
Joseph Toynbee and his son Arnold: unpublished manuscript written by Adam Politzer
Authors: Mudry Albert , Kutter Jurg
Published: March 2004

In 1914, Adam Politzer (1835–1920) was invited to the Viennese Toynbee Hall to give a lecture. To prepare for his lecture, Politzer wrote a manuscript of 22 pages, seven of them are particularly interesting
concerning biographical information on Joseph and Arnold Toynbee. These seven pages are presented in translation from German to English. Politzer particularly emphasizes the social qualities of these two men. This manuscript is representative of his high regard for Joseph and Arnold Toynbee. It completes the few existing biographies of Joseph Toynbee.
Auricular pseudocyst in the tropics: a multi-racial Singapore experience
Authors: Tan B. Y. B. , Hsu P. P.
Published: March 2004

Endochondral pseudocyst of the auricle is an uncommon condition that affects predominantly Chinese males, with many reports studying this condition in homogenous Chinese populations. There have been few large-scale reports describing the features of this disease among the other Asian groups. In one of the largest series described to date, we report the epidemiological features, clinico-pathologic characteristics, and success of surgical treatment in 40 patients of different Asian groups presenting with pseudocyst of the auricle. Results showed a Chinese predominance (90 per cent), followed by Malays (five per cent) and Eurasians (five per cent). All had unilateral presentations apart from one patient. Most (55 per cent) presented within two weeks of auricular swelling. Few (10 per cent) had a history of trauma. The pseudocysts predominantly affected the concha (61 per cent). Surgery comprised excision of the anterior wall followed by local pressure application. Only 2.5 per cent had recurrence after surgery. These findings confirm earlier understood features of this disease while revealing some notable variations.
Radiological study of the intumescentia septi nasi anterior
Authors: Arslan Mubeccel , Muderris Togay , Muderris Suphi
Published: March 2004

Intumescentia septi nasi anterior (ISNA) is a common anatomical variation that is not routinely noticed by surgeons or radiologists. ISNA is a mucosal bulging located on each side of the anterior part of
the septum. The aim of this study was to investigate the prevalence of ISNA in different ages and sexes.

In this study, computerized tomography (CT) scans of the paranasal sinus were obtained from 595
patients who had symptoms of chronic sinusitis. Among 595 subjects, ISNA was found in 332 (55.79 per cent) of subjects. It was found more frequently in males than females in every age group.

Although ISNA is a common anatomical variation, it is generally overlooked. This is the first report on ISNA in different age groups and sexes.
Endoscopic radiosurgical posterior transverse cordotomy for bilateral median vocal fold immobility
Authors: Elsherief Sayed , Elsheikh Mohamed Nasser
Published: March 2004

The objectives in treatment of bilateral vocal fold immobility (BVFI) are to achieve adequate airway, preservation of voice quality and laryngeal competence. The present prospective study was designed to evaluate precisely the efficiency and long-term clinical outcome in a series of 13 patients with irreversible BVFI, consecutively managed with endoscopic radiosurgical posterior transverse cordotomy (ERPTC). The operation was performed endoscopically using an Ellman Radiosurgical Instrument and a specially designed electrode. Pre- and post-operative inspiratory function measurements and acoustical vocal analysis were conducted on the patients and were tested for potential statistical relation to successful rehabilitation of the airway. One-step, successful restoration of the airway was achieved in all patients. The post-operative improvement of spirometric values was statistically significant (p < 0.0001), and during the follow-up period of (six to 30) months, airway stability was demonstrated in all patients. In terms of acoustic analysis a non-significant difference was found between pre- and post-operative vocal functions (p > 0.05). This management approach offers an alternative to laser procedures, it provides a ’one-stage’ solution for permanent bilateral vocal fold immobility, and avoids terminal loss of voice quality. The authors’ data confirm the safety, ease of performance, and efficiency of ERPTC in patients with bilateral immobile vocal folds.
Antibiotic prophylaxis in clean neck dissections
Authors: Seven Huseyin , Sayin Ibrahim , Turgut Suat
Published: March 2004

This study was designed to evaluate the effects of a prophylactic antibiotic regimen on the incidence of wound infection after clean neck dissections. A prospective series of 57 patients undergoing clean neck dissections with the use of perioperative ampicillin-sulbactam for 24 hours was compared with an historical control group of 51 patients undergoing clean neck dissections with no perioperative antibiotic use. The outcome variable was the incidence of post-operative wound infection. The two groups were similar for factors reported to influence the rate of post-operative wound infection. Wound infection occurred in one patient (1.7 per cent) in the study group and in seven patients (13.3 per cent) in the control group, the difference was statistically significant (p = 0.02). These data suggest that the use of a perioperative antibiotic for 24 hours in patients undergoing clean neck dissection results in significant reduction in the incidence of post-operative wound infection.
Survey of current undergraduate otolaryngology training in the United Kingdom
Authors: Mace A. D. , Narula A. A.
Published: March 2004

The General Medical Council’s core curriculum model for undergraduate medical training is leading to changes in the way specialist subjects are taught. A postal survey was undertaken to evaluate the current state of undergraduate clinical teaching in otolaryngology in the United Kingdom. Data were received from all 27 medical schools. Six medical schools (22 per cent) do not have a compulsory ENT attachment, although three of these offer an optional attachment. Fifty-eight per cent of all ENT attachments are combined with other specialities including dermatology, ophthalmology and neurology. The average length of time spent with the ENT department during medical school training is one and a half weeks. Forty-two per cent of students do not have a formal assessment of their clinical skills or knowledge at the end of such attachments.
Utilization of intestinal clamps for precise cutting of the pectoralis major muscle while raising a myocutaneous flap
Authors: Chaturvedi P.
Published: March 2004

A variety of approaches have been employed for the reconstruction of head and neck defects and most of the techniques involve the use of arterialized vascular flaps alone, or in conjunction with other regional or local tissues. We frequently use a pectoralis major myocutaneous (PMMC) flap in our hospital in addition to other pedicled or free tissue transfers. A PMMC flap is a reliable flap with acceptable complications, needs a small learning curve, takes less time, and does not require additional investment (i.e. microscopes, loops etc). The disadvantages of the PMMC flap is that it has a restricted arc of rotation, gives a cosmetically unacceptable bulk in the neck, it is difficult in females and causes significant shoulder dysfunction. We have made a small improvization in the flap-raising technique which is helpful for the surgeon. This involves utilization of intestinal clamps to hold and cut the pectoralis major muscle.
Post-traumatic cutaneous meningioma
Authors: Borggreven Pepijn A. , de Graaf Floris H. , van der Valk Paul , Leemans C. René
Published: March 2004

Cutaneous meningiomas are extremely rare tumours and their diagnosis is difficult. We describe the case of a patient who developed a paranasal swelling after head trauma and associated fractures in the same region years before. Histopathological examination of an incisional biopsy revealed the diagnosis of cutaneous meningioma. After one and a half years’ follow up, surgical excision was performed because of progressive growth of the tumour and associated aesthetic problems. Extracranial meningiomas can develop probably secondary to trapping of meningeal tissue after trauma. If there is no intracranial connection surgical removal can be considered.
Plasma γ-Globin Gene Expression Suggests that Fetal Hematopoietic Cells Contribute to the Pool of Circulating Cell-Free Fetal Nucleic Acids during Pregnancy
Authors: Wataganara Tuangsit , LeShane Erik S , Chen Angela Y , Borgatta Lynn , Peter Inga , Johnson Kirby L , Bianchi Diana W
Published: March 2004

Background: Reports of placental mRNA sequences in the plasma of pregnant women suggest that the placenta is the predominant source of cell-free fetal nucleic acids in maternal plasma during pregnancy. We developed an assay for γ-globin mRNA concentrations to determine whether hematopoietic cells also contribute to the pool of fetal mRNA in maternal plasma.

Methods: Frozen paired plasma samples obtained from 40 women before and within 20 min after elective first-trimester termination of pregnancy (TOP) were analyzed. Fresh plasma samples from eight nonpregnant individuals were included as controls. Plasma γ-globin mRNA was measured by use of real-time reverse transcription-PCR and analyzed with gestational age. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA was used to confirm the presence of cell-free RNA in each sample.

Results: γ-Globin and GAPDH mRNA sequences were detected in every plasma sample. The concentrations of both messages were significantly increased in pregnancy (P <0.01). The concentrations of γ-globin mRNA were decreased in most women after TOP, but γ-globin mRNA was increased in some patients when TOP was performed later than 9 weeks of gestation.

Conclusions: γ-Globin mRNA sequences can be detected and measured in fresh and frozen plasma samples. Plasma γ-globin and GAPDH mRNA concentrations are affected by pregnancy. The increased posttermination γ-globin mRNA concentrations seen in some patients suggest that the source of this message is fetal hematopoietic cells. Further study in pregnant women after 9 weeks of gestation is necessary to evaluate the potential of γ-globin mRNA as a marker for fetomaternal hemorrhage.
Binding Sites of γ-Secretase Inhibitors in Rodent Brain: Distribution, Postnatal Development, and Effect of Deafferentation
Authors: Yan Xiao-Xin , Li Tong , Rominger Cynthia M. , Prakash Shimoga R. , Wong Philip C. , Olson Richard E. , Zaczek Robert , Li Yu-Wen
Published: March 2004

γ-Secretase is a multimeric complex consisted of presenilins (PSs) and three other proteins. PSs appear to be key contributors for the enzymatic center, the potential target of a number of recently developed γ-secretase inhibitors. Using radiolabeled and unlabeled inhibitors as ligands, this study was aimed to determine thein situdistribution of γ-secretase in the brain. Characterization using PS-1 knock-out mouse embryos revealed 50 and 80% reductions of γ-secretase inhibitor binding density in the heterozygous (PS-1+/–) and homozygous (PS-1–/–) embryos, respectively, relative to the wild type (PS-1+/+). The pharmacological profile from competition binding assays suggests that the ligands may target at the N- and C-terminal fragments of PS essential for γ-secretase activity. In the adult rat brain, the binding sites existed mostly in the forebrain, the cerebellum, and discrete brainstem areas and were particularly abundant in areas rich in neuronal terminals, e.g., olfactory glomeruli, CA3–hilus area, cerebellar molecular layer, and pars reticulata of the substantia nigra. In the developing rat brain, diffuse and elevated expression of binding sites occurred at the early postnatal stage relative to the adult. The possible association of binding sites with neuronal terminals in the adult brain was further investigated after olfactory deafferentation. A significant decrease with subsequent recovery of binding sites was noted in the olfactory glomeruli after chemical damage of the olfactory epithelium. The findings in this study support a physiological role of PS or γ-secretase complex in neuronal and synaptic development and plasticity.
Nuclear Factor-κB Modulates the p53 Response in Neurons Exposed to DNA Damage
Authors: Aleyasin Hossein , Cregan Sean P. , Iyirhiaro Grace , O'Hare Michael J. , Callaghan Steve M. , Slack Ruth S. , Park David S.
Published: March 2004

Previous studies have shown that DNA damage-evoked death of primary cortical neurons occurs in a p53 and cyclin-dependent kinase-dependent (CDK) manner. The manner by which these signals modulate death is unclear. Nuclear factor-κB (NF-κB) is a group of transcription factors that potentially interact with these pathways. Presently, we show that NF-κB is activated shortly after induction of DNA damage in a manner independent of the classic IκB kinase (IKK) activation pathway, CDKs, ATM, and p53. Acute inhibition of NF-κB via expression of a stable IκB mutant, downregulation of the p65 NF-κB subunit by RNA interference (RNAi), or pharmacological NF-κB inhibitors significantly protected against DNA damage-induced neuronal death. NF-κB inhibition also reduced p53 transcripts and p53 activity as measured by the p53-inducible messages, Puma and Noxa, implicating the p53 tumor suppressor in the mechanism of NF-κB-mediated neuronal death. Importantly, p53 expression still induces death in the presence of NF-κB inhibition, indicating that p53 acts downstream of NF-κB. Interestingly, neurons cultured from p65 or p50 NF-κB-deficient mice were not resistant to death and did not show diminished p53 activity, suggesting compensatory processes attributable to germline deficiencies, which allow p53 activation still to occur. In contrast to acute NF-κB inhibition, prolonged NF-κB inhibition caused neuronal death in the absence of DNA damage. These results uniquely define a signaling paradigm by which NF-κB serves both an acute p53-dependent pro-apoptotic function in the presence of DNA damage and an anti-apoptotic function in untreated normal neurons.
Axon Branching and Synaptic Bouton Phenotypes in GABAergic Nonpyramidal Cell Subtypes
Authors: Karube Fuyuki , Kubota Yoshiyuki , Kawaguchi Yasuo
Published: March 2004

GABAergic nonpyramidal cells, cortical interneurons, consist of heterogeneous subtypes differing in their axonal field and target selectivity. It remains to be investigated how the diverse innervation patterns are generated and how these spatially complicated, but synaptically specific wirings are achieved. Here, we asked whether a particular cell type obeys a specific branching and bouton arrangement principle or differs from others only in average morphometric values of the morphological template common to nonpyramidal cells. For this purpose, we subclassified nonpyramidal cells within each physiological class by quantitative parameters of somata, dendrites, and axons and characterized axon branching and bouton distribution patterns quantitatively. Each subtype showed a characteristic set of vertical and horizontal bouton spreads around the somata. Each parameter, such as branching angles, internode or interbouton intervals, followed its own characteristic distribution pattern irrespective of subtypes, suggesting that nonpyramidal cells have the common mechanism for formation of the axon branching pattern and bouton arrangement. Fitting of internode and interbouton interval distributions to the exponential indicated their apparent random occurrence. Decay constants of the fitted exponentials varied among nonpyramidal cells, but each subtype expressed a particular set of interbouton and internode interval averages. The distinctive combination of innervation field shape and local axon phenotypes suggests a marked functional difference in the laminar and columnar integration properties of different GABAergic subtypes, as well as the subtype-specific density of inhibited targets.
Corticofugal Gating of Auditory Information in the Thalamus: AnIn VivoIntracellular Recording Study
Authors: Yu Yan-Qin , Xiong Ying , Chan Ying-Shing , He Jufang
Published: March 2004

In the present study, we investigated the auditory responses of the medial geniculate (MGB) neurons, throughin vivointracellular recordings of anesthetized guinea pigs, while the auditory cortex was electrically activated. Of the 63 neurons that received corticofugal modulation of the membrane potential, 30 received potentiation and 33 received hyperpolarization. The corticofugal potentiation of the membrane potential (amplitude, mean ± SD, 8.6 ± 5.5 mV; duration, 125.5 ± 75.4 msec) facilitated the auditory responses and spontaneous firing of the MGB neurons. The hyperpolarization of –11.3 ± 4.9 mV in amplitude and 210.0 ± 210.1 msec in duration suppressed the auditory responses and spontaneous firing of the MGB neurons. Four of the five neurons that were histologically confirmed to be located in the lemniscal MGB received corticofugal facilitatory modulation, and all of the four neurons that were confirmed to be located in the non-lemniscal MGB received corticofugal inhibitory modulation. The present intracellular recording provides novel results on how the corticofugal projection gates the sensory information in the thalamus: via the spatially selective depolarization of lemniscal MGB neurons and hyperpolarization of non-lemniscal MGB neurons. It is speculated that the systematic selectivity of facilitation and inhibition over the lemniscal and non-lemniscal MGB is related to the attention shift within the auditory modality and across the sensory modalities.
Protein Kinase A Activation Promotes Plasma Membrane Insertion of DCC from an Intracellular Pool: A Novel Mechanism Regulating Commissural Axon Extension
Authors: Bouchard Jean-François , Moore Simon W. , Tritsch Nicolas X. , Roux Philippe P. , Shekarabi Masoud , Barker Philip A. , Kennedy Timothy E.
Published: March 2004

Protein kinase A (PKA) exerts a profound influence on axon extension during development and regeneration; however, the molecular mechanisms underlying these effects of PKA are not understood. Here, we show that DCC (deleted in colorectal cancer), a receptor for the axon guidance cue netrin-1, is distributed both at the plasma membrane and in a pre-existing intracellular vesicular pool in embryonic rat spinal commissural neurons. We hypothesized that the intracellular pool of DCC could be mobilized to the plasma membrane and enhance the response to netrin-1. Consistent with this, we show that application of netrin-1 causes a modest increase in cell surface DCC, without increasing the intracellular concentration of cAMP or activating PKA. Intriguingly, activation of PKA enhances the effect of netrin-1 on DCC mobilization and increases axon extension in response to netrin-1. PKA-dependent mobilization of DCC to the plasma membrane is selective, because the distributions of transient axonal glycoprotein-1, neural cell adhesion molecule, and trkB are not altered by PKA in these cells. Inhibiting adenylate cyclase, PKA, or exocytosis blocks DCC translocation on PKA activation. These findings indicate that netrin-1 increases the amount of cell surface DCC, that PKA potentiates the mobilization of DCC to the neuronal plasma membrane from an intracellular vesicular store, and that translocation of DCC to the cell surface increases axon outgrowth in response to netrin-1.
Suprachiasmatic Nuclei Grafts Restore the Circadian Rhythm in the Paraventricular Nucleus of the Hypothalamus
Authors: Tousson Ehab , Meissl Hilmar
Published: March 2004

The mammalian suprachiasmatic nucleus (SCN) controls the circadian rhythm of many physiological and behavioral events by an orchestrated output of the electrical activity of SCN neurons. We examined the propagation of output signals from the SCN into the hypothalamus, especially into the region of the paraventricular nucleus, through multimicroelectrode recordings using acute and organotypic brain slices. Circadian rhythms in spontaneous firing rate with a period close to 24 hr were demonstrated in the SCN, in directly adjacent hypothalamic regions, and in the region of the paraventricular nucleus of the hypothalamus, an important center for the integration of neuroendocrine, homeostatic, and autonomic functions. The activity rhythms recorded from structures outside of the SCN were in phase with the rhythms in the SCN. Cyclic information in the hypothalamus was lost after ablation of the SCN but could be restored by SCN grafts, indicating that a humoral factor is responsible for the restoration of circadian rhythmicity in the absence of neural connections. Periodic application of arginine–vasopressin (AVP) provided evidence that AVP can induce rhythmicity in the hypothalamus. These data indicate that the SCN uses a dual (neuronal and humoral) mechanism for communication with its targets in the brain.
Spike Generator Limits Efficiency of Information Transfer in a Retinal Ganglion Cell
Authors: Dhingra Narender K. , Smith Robert G.
Published: March 2004

The quality of the signal a retinal ganglion cell transmits to the brain is important for preception because it sets the minimum detectable stimulus. The ganglion cell converts graded potentials into a spike train with a selective filter but in the process adds noise. To explore how efficiently information is transferred to spikes, we measured contrast detection threshold and increment threshold from graded potential and spike responses of brisk-transient ganglion cells. Intracellular responses to a spot flashed over the receptive field center of the cell were recorded in an intact mammalian retina maintainedin vitroat 37°C. Thresholds were measured in a single-interval forced-choice procedure with an ideal observer. The graded potential gave a detection threshold of 1.5% contrast, whereas spikes gave 3.8%. The graded potential also gave increment thresholds approximately twofold lower and carried ∼60% more gray levels. Increment threshold “dipped” below the detection threshold at a low contrast (<5%) but increased rapidly at higher contrasts. The magnitude of the “dipper” for both graded potential and spikes could be predicted from a threshold nonlinearity in the responses. Depolarization of the cell by current injection reduced the detection threshold for spikes but also reduced the range of contrasts they can transmit. This suggests that contrast sensitivity and dynamic range are related in an essential trade-off.
Role of Hippocampal CA3 μ-Opioid Receptors in Spatial Learning and Memory
Authors: Meilandt William J. , Barea-Rodriguez Edwin , Harvey Stephen A. K. , Martinez Joe L.
Published: March 2004

The dorsal CA3 region of the hippocampus is unique in its connectivity, sensitivity to neurotoxic lesions, and its ability to encode and retrieve episodic memories. Computational models of the CA3 region predict that blocking mossy-fiber and/or perforant path activity to CA3 would cause impairments in learning and recall of spatial memory, respectively. Because the CA3 region contains μ-opioid receptors and receives inputs from the mossy-fiber and lateral perforant pathways, both of which contain and release opioid peptides, we tested the hypothesis that inactivating μ-opioid receptors in the CA3 region would cause spatial learning and memory impairments and retrieval deficits. In this study, male Sprague Dawley rats were trained in a Morris water maze after a single bilateral intrahippocampal injection of either saline or the selective and irreversible μ-opioid receptor antagonist β-funaltrexamine (β-FNA) into area CA3. We found that μ-opioid receptor binding decreased 24 hr after β-FNA injection and returned to control levels 11 d after injection. Injections of β-FNA into the CA3 region, but not into the ventricles, caused a significant impairment in the acquisition of spatial learning without causing sensory or motor deficits. New learning was not affected once μ-opioid receptor levels replenished (>11 d after injection). In pretrained animals, β-FNA significantly impaired spatial memory retrieval and new (reversal) learning. These data are consistent with theoretical models of CA3 function and suggest that CA3 μ-opioid receptors play an important role in the acquisition and retrieval of spatial memory.
Compatibilization of water borne poly(ethylene oxide)‐silica hybrids
Authors: Manaf Ishak , Mascia Leno
Published: March 2004

Organic‐inorganic hybrid materials, incorporating nanostructured silica networks within a poly(ethylene oxide) matrix (PEO), were produced via the sol–gel process from water solution mixtures of poly(ethylene oxide) and prehydrolyzed tetraethylorthosilicate (TEOS) in the presence of a trialkoxysilane compatibilization agent, γ‐glycidyloxypropyltrimethoxysilane (GOTMS). These mixtures were cast into films by evaporating the solvent and finally drying in an air‐circulating oven at 60°C. By varying the composition of the alkoxysilane solution mixture and mixing conditions, different morphologies were obtained, ranging from semi‐interpenetrating networks of PEO within highly cross‐linked siloxane domains, to finely dispersed nanostructured systems exhibiting either co‐continuous or particulate structure. The effects of pH, type of solvents, mixing temperatures and time, as well as the concentration of the compatibilization agent was found to be extremely important in controlling the morphology and properties of the final PEO‐SiO2hybrid films. © 2004 Wiley Periodicals, Inc. Adv Polym Techn 23: 125–134, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/adv.20001
Evaluation of performance of polyurethanes based on hydroxy alkylated cardanol formaldehyde resins under aging conditions
Authors: Sathiyalekshmi K. , Gopalakrishnan S.
Published: March 2004

Rigid polyurethanes were synthesized using hydroxy alkylated cardanol formaldehyde and hydroxy alkylated dimerized‐cardanol formaldehyde resins and dicyclo hexyl methane diisocyanate. The studies on the aging (hydrolytic stability, absorption of water/toluene, chemical resistance, dimensional stability, and thermal stability) of these polyurethanes reveal appreciable stability. The performance of these polyurethanes was compared with elastoplastic polyurethanes synthesized with the addition of commercially available poly(ethylene glycol). The rigid polyurethanes are distinctly stable than elastoplastic polyurethanes under various aging conditions. © 2004 Wiley Periodicals, Inc. Adv Polym Techn 23: 91–102, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/adv.20005
Quantitation of Nonextractable Anthropogenic Quantitation of Nonextractable Anthropogenic Sediments after Chemical Degradation
Authors: Schwarzbauer Jan , Ricking Mathias , Littke Ralf
Published: March 2004

Four highly contaminated sediment samples obtained from three sampling locations of the Teltow Canal, Berlin, were investigated by quantitation of extractable and nonextractable organic contaminants. The selection of the anthropogenic contaminants (including chlorinated and brominated naphthalenes, 2, 4, 6‐tribromoaniline, phthalates, tri‐n‐butylphosphate, 2, 2, 4‐trimethyl‐1, 3‐pentanediol diisobutyrate, bisphenol A, butylated nitrophenols, 4‐nitrobenzoic acid, galaxolide, and tonalide) based on the results of extended GC‐MS screening analyses applied to the extracts of the sediment samples as well as to the extracts derived from selective chemical degradation procedures. In detail, alkaline hydrolyses, BBr3‐treatment and RuO4‐oxidation were applied to the pre‐extracted sediment samples in both a separate and a sequential mode.
POLG mutations associated with Alpers' syndrome and mitochondrial DNA depletion
Authors: Naviaux Robert K. , Nguyen Khue V.
Published: March 2004

Alpers' syndrome is a fatal neurogenetic disorder first described more than 70 years ago. It is an autosomal recessive, developmental mitochondrial DNA depletion disorder characterized by deficiency in mitochondrial DNA polymerase γ (POLG) catalytic activity, refractory seizures, neurodegeneration, and liver disease. In two unrelated pedigrees of Alpers' syndrome, each affected child was found to carry a homozygous mutation in exon 17 of the POLG locus that led to a Glu873Stop mutation just upstream of the polymerase domain of the protein. In addition, each affected child was heterozygous for the G1681A mutation in exon 7 that led to an Ala467Thr substitution in POLG, within the linker region of the protein. Ann Neurol 2004
8‐Oxabicyclo[3.2.1]oct‐6‐en‐3‐one: Anwendungen in der asymmetrischen Synthese polyoxygenierter Bausteine
Authors: Hartung Ingo V. , Hoffmann H. Martin R.
Published: March 2004

Die Entdeckung und das Design von zuverlässigen und effizienten Methoden zum Aufbau chiraler Bausteine spielt in der modernen Naturstoffsynthese eine entscheidende Rolle. 8‐Oxabicyclo[3.2.1]oct‐6‐en‐3‐one sind leicht zugängliche Gerüste mit definierten stereochemischen Eigenschaften, die in Nicht‐Aldolansätzen zur Herstellung chiraler Bausteine genutzt werden. Strategien zu ihrer enantioselektiven Synthese umfassen Methoden für asymmetrische Cycloadditionen, Desymmetrisierungsprotokolle und “Racemic‐Switch‐Operationen”. Die Ergebnisse dieser Arbeiten werden in diesem Aufsatz präsentiert und eingeschätzt.
Cover Picture: Enzymatic Behavior by Intercalating Molecules in a Template‐Directed Ligation Reaction (Angew. Chem. Int. Ed. 15/2004)
Authors: Jain Swapan S. , Anet Frank A. L. , Stahle Christopher J. , Hud Nicholas V.
Published: March 2004

Intercalation‐mediated assembly is a powerful method for the template‐directed ligation of oligonucleotides. In their Communication on page 2004 ff., Hud and co‐workers demonstrate that proflavine, drawn in yellow, enhances the rate of oligonucleotide ligation by three orders of magnitude. The possibility that small molecules played a similar role in the origin of life is suggested by the cover‐picture background, which is from M. C. Escher's woodcut The Second Day of Creation (1925).
Using N‐grams for Arabic text searching
Authors: Mustafa Suleiman H. , Al‐Radaideh Qasem A.
Published: March 2004

N‐grams have been widely investigated for a number of text processing and retrieval applications. This article examines the performance of the digram and trigram term conflation techniques in the context of Arabic free text retrieval. It reports the results of using the N‐gram approach for a corpus of thousands of distinct textual words drawn from a number of sources representing various disciplines. The results indicate that the digram method offers a better performance than trigram with respect to conflation precision and conflation recall ratios. In either case, the N‐gram approach does not appear to provide an efficient conflation approach due to the peculiarities imposed by the Arabic infix structure that reduces the rate of correct N‐gram matching.
Novel Methodologies for the Synthesis of Cyclic Carbonates
Authors: Yoshida Masahiro , Ihara Masataka
Published: March 2004

Cyclic carbonates are valuable compounds that have applications in a variety of chemical fields. Methodologies for the synthesis of cyclic carbonates are well investigated in recent years, and the most successful and popular procedure is the utilization of CO2. This paper presents recent progress in the synthesis of cyclic carbonates by a CO2‐fixation process, which involves novel palladium‐catalyzed CO2‐recycling reactions.
A Catalytic Antibody against a Tocopherol Cyclase Inhibitor
Authors: Manetsch Roman , Zheng Lei , Reymond Martine T. , Woggon Wolf‐Dietrich , Reymond Jean‐Louis
Published: March 2004

The cyclic ammonium cation 5 and its guanidinium analogue 4 are inhibitors of tocopherol cyclase. Monoclonal antibodies were raised against protein conjugates of the haptens 1–3 and screened for catalytic reactions with alkene 8, a short chain analogue of the natural substrate phytyl‐hydroquinone 6, and its enol ether analogues 10 a, b. Antibody 16E7 raised against hapten 3 was found to catalyze the hydrolysis of Z enol ether 10 a to form hemiacetal 12 with an apparent rate acceleration of kcat/kuncat=1400. Antibody 16E7 also catalyzed the elimination of Kemp's benzisoxazole 59. The absence of cyclization in the reaction of enol ether 10 a was attributed to the competition of water molecules for the oxocarbonium cation intermediate within the antibody binding pocket. Hapten and reaction design features contributing to this outcome are discussed. Antibody 16E7 provides the first example of a carboxyl group acting both as an acid in an intrinsically acid‐catalyzed process and as a base in an intrinsically base‐catalyzed process, as expected from first principles. In contrast to the many examples of general‐acid‐catalyzed processes known to be catalyzed by catalytic antibodies, the specific‐acid‐catalyzed cyclization of phytyl‐hydroquinone 6 or its analogue 8 still eludes antibody catalysis.
A General Study of [(η5‐Cp′)2Ti(η2‐Me3SiC2SiMe3)]‐Catalyzed Hydroamination of Terminal Alkynes: Regioselective Formation of Markovnikov and Anti‐Markovnikov Products and Mechanistic Explanation (Cp′=C5H5, C5H4Et, C5Me5)
Authors: Tillack Annegret , Jiao Haijun , Garcia Castro Ivette , Hartung Christian G. , Beller Matthias
Published: March 2004

A general study of the regioselective hydroamination of terminal alkynes in the presence of [(η5‐Cp)2Ti(η2‐Me3SiC2SiMe3)] (1), [(η5‐CpEt)2Ti(η2‐Me3SiC2SiMe3)] (CpEt=ethylcyclopentadienyl) (2), and [(η5‐Cp*)2Ti(η2‐Me3SiC2SiMe3)] (Cp*=pentamethylcyclopentadienyl) (3) is presented. While aliphatic amines give mainly the anti‐Markovnikov products, anilines and aryl hydrazines yield the Markovnikov isomer as main products. Interestingly, using aliphatic amines such as n‐butylamine and benzylamine the different catalysts lead to a significant change in the observed regioselectivity. Here, for the first time a highly selective switch from the Markovnikov to the anti‐Markovnikov product is observed simply by changing the catalyst. Detailed theoretical calculations for the reaction of propyne with different substituted anilines and tert‐butylamine in the presence of [(η5‐C5H5)Ti(NR)(NHR)] (R=4‐C6H4X; X=H, F, Cl, CH3, 2,6‐dimethylphenyl) reveal that the experimentally observed regioselectivity is determined by the relative stability of the corresponding π‐complexes 10. While electrostatic stabilization favors the Markovnikov performance for aniline, the steric repulsive destabilization disfavors the Markovnikov performance for tert‐butylamine.
Parvalbumin‐containing interneurons in the basolateral amygdala express high levels of the α1 subunit of the GABAA receptor
Authors: McDonald Alexander Joseph , Mascagni Franco
Published: March 2004

The basolateral amygdala (ABL) is essential for the amnestic effects of benzodiazepines in aversive learning tasks. Because the α1 subunit of the γ‐aminobutyric acid (GABA)A receptor is critical for these amnestic actions, knowledge of the neuronal localization of this subunit in the ABL should contribute to an understanding of the candidate neuronal mechanisms involved. To examine this question, we used dual‐labeling immunohistochemical techniques to study the localization of the α1 subunit in the ABL. Our results suggest that the α1 subunit of the GABAA receptor is localized primarily in GABAergic interneurons in the ABL at the somal level, although the intense neuropil staining in the lateral nucleus suggests that distal dendrites of pyramidal projection neurons in this nucleus may also contain high levels of the α1 subunit. The great majority of α1‐immunoreactive interneurons also exhibit immunoreactivity for the β2/3 subunits of the GABAA receptor. Parvalbumin‐positive (PV+) interneurons are the main interneuronal subpopulation exhibiting α1 immunoreactivity, but some calretinin‐positive interneurons also express this subunit. These data suggest that certain subpopulations of GABAergic interneurons in the ABL, especially PV+ cells, receive a robust GABAergic innervation. Because the most likely source of this innervation is intrinsic, these results suggest that PV+ interneurons could constitute an important component of interneuronal networks in the ABL. These networks may be critical for the generation of synchronized rhythmic oscillations involved in consolidation of emotional memories. The activation of α1‐containing GABAA receptors in the ABL by benzodiazepines may disrupt rhythmic oscillations critical for memory consolidation. J. Comp. Neurol. 473:137–146, 2004. © 2004 Wiley‐Liss, Inc.
Increased citrullinated glial fibrillary acidic protein in secondary progressive multiple sclerosis
Authors: Nicholas Anthony P. , Sambandam Thiagarajan , Echols Joshua D. , Tourtellotte Wallace W.
Published: March 2004

In this study, we demonstrate that grossly unaffected white matter from secondary progressive multiple sclerosis (SP‐MS) patients is heavily citrullinated, as compared to normal white matter from control patients. Citrullination was most pronounced at plaque interfaces and was shown to colocalize with glial fibrillary acidic protein (GFAP)‐immunoreactivity using dual color immunofluorescence. In contrast, the plaques themselves weakly stained for citrullinated proteins compared to control white matter and usually contained a blood vessel with surrounding astrocytes that were positive both for citrullinated proteins and GFAP. In SP‐MS brain samples, but not in normal brains, long fibers of colocalized GFAP‐ and citrullinated proteins extended into the gray matter. Increased numbers of astrocytes containing citrullinated proteins and GFAP were also present at the junction between the gray and white matter in SP‐MS brains. Western blot analysis of acidic brain proteins from nonplaque‐containing white matter showed upregulation of multiple citrullinated GFAP proteins in SP‐MS brains as compared to controls. Our results demonstrate that increased amounts of citrullinated GFAP are present in SP‐MS brains, but also shows that these proteins are present in areas of MS brains that were grossly normal appearing. These data raise the possibility that citrullination of GFAP contributes to the pathophysiology of MS. J. Comp. Neurol. 473:128–136, 2004. © 2004 Wiley‐Liss, Inc.