bluuebunny/crossref_metadata_2025 huggingface dataset:
Laryngeal Nerve Function after Total Laryngeal Transplantation
Authors: Lorenz Robert R. , Hicks Douglas M. , Shields Robert W. , Fritz Michael A. , Strome Marshall
Published: December 2004

The first successful composite human laryngeal transplantation was performed by a team led by the senior author on January 4, 1998. The recipient was a 40‐year‐old male who had sustained a crush injury to his larynx 20 years prior, rendering him aphonic. Multiple previous attempts for reconstruction at an outside hospital were unsuccessful. The donor was a 40‐year‐old male who had died from a ruptured cerebral aneurysm. The specifics of the procedure have been detailed elsewhere.1 Throughout the patient's postoperative course, serial fiberoptic evaluations and voice testing were performed to evaluate laryngeal reinnervation reflected in phonatory function. We herein report the results of these exams, as well as the results of electromyographic recordings of the laryngeal musculature 4 years posttransplantation.
Surface Electromyographic Studies of Swallowing in Normal Subjects: A Review of 440 Adults. Report 3. Qualitative Data
Authors: Vaiman Michael , Eviatar Ephraim , Segal Samuel
Published: December 2004

OBJECTIVE

Surface electromyographic studies were performed on 440 normal adults to describe and evaluate different types of normal swallows clinically useful for ENT department.

STUDY DESIGN

Prospective observational study of healthy volunteers.

METHODS

EMG recordings were made using stick‐on surface electrodes. Rectified and filtered EMG signals were evaluated. Parameters evaluated include the graphic configuration of activity of the orbicularis oris, masseter, submental group, and infrahyoid muscles, the last 2 covered by platysma, during single swallowing and continuous drinking. Four tests were examined: voluntary saliva swallows, voluntary separate swallows as normal, voluntary separate swallows of excessive amount of water (20 mL), drinking of 100 mL of water. Graphic recording of activity of the above‐mentioned muscles during swallowing and drinking were evaluated for groups of adults of different ages.

RESULTS

There are several types of normal swallows as seen at the surface EMG records. There was no difference between EMG recordings of male and female swallows. Only group of elderly patients (age 70+) shows age‐induced differences in recorded swallows. There are two main types of normal swallow: single‐share and double‐share swallows. The oral phase of swallowing, being under conscious control, is very variable and should not be taken into consideration during evaluation of records. Final oral, pharyngeal, and initial esophageal stages of swallowing can be defined and evaluated at the rectified and filtered surface EMG record.

CONCLUSION

The normal muscle activity during swallows and drinking has several graphic patterns which can be identified and described similar to EKG records when surface EMG is rectified and filtered. The method of EMG recording is quick and simple, and can be used for screening and evaluation purposes in outpatient and inpatient ENT departments. These parameters represent activities required for normal deglutition, and can be used to identify abnormalities in ENT patients, and provide a basis for comparison of swallowing performance both within and between patients. These normal data form a valuable basis for future comparison with patients in pre‐ and postoperative stages and in EMG monitoring during ENT treatment.
A Diagnostic Paradigm for Childhood Idiopathic Sensorineural Hearing Loss
Authors: Preciado Diego A. , Lim Lynne H.Y. , Cohen Aliza P. , Madden Colm , Myer David , Ngo Chris , Bradshaw John K. , Lawson Louise , Choo Daniel I. , Greinwald John H.
Published: December 2004

OBJECTIVE

Our objective was to determine the diagnostic yield of laboratory testing, radiological imaging, and GJB2 mutation screening in a large cohort of patients with differing severities of idiopathic sensorineural hearing loss (SNHL).

DESIGN AND SETTING

We undertook a retrospective study of patients presenting with SNHL at our institution from 1993 to 2002.

RESULTS

Laboratory testing had an extremely low yield. Patients with unilateral SNHL had a significantly higher imaging yield than those with bilateral. The diagnostic yield of GJB2 screening was significantly higher in patients with severe to profound SNHL than in those with less severe SNHL. However, a relatively large number of patients with mild to moderate SNHL had positive GJB2 screens.

CONCLUSIONS

Based on diagnostic yields, we propose a cost‐effective stepwise diagnostic paradigm to replace the more commonly used and costly simultaneous testing approach. EBM rating: C. (Otolaryngol Head Neck Surg 2004;131: 804–9.)
Endoscopic Sinus Surgery in Patients Older than Sixty
Authors: Colclasure J. Chris , Gross Charles W. , Kountakis Stilianos E.
Published: December 2004

OBJECTIVE

Rhinosinusitis is the sixth most common chronic condition of the elderly. Functional endoscopic sinus surgery (FESS) has developed over the last 20 to 30 years into a widely accepted treatment modality for chronic rhinosinusitis in adults who have failed maximal medical management. The aim of this study was investigate the safety and efficacy of FESS in the geriatric population as compared to that of the adult population.

METHODS

Retrospective review of prospective measurement of outcomes in consecutive patients over 60 years of age who underwent FESS. Fifty‐six patients over 60 years of age underwent FESS and were evaluated preoperatively and postoperatively at 3, 6, and 12 months with the Sino‐Nasal Outcome Test‐20 (SNOT‐20) questionnaire, and a rigid nasal endoscopy scoring system. Data analysis was performed using the Student's t test to compare mean scores. Any complications were noted.

RESULTS

Patients evaluated by the SNOT‐20 scoring system experienced 64% improvement of symptom scores at 3 months, 73% improvement at 6 months, and 75% improvement at 12 months. Rigid nasal endoscopy scores improved by 76% at 3 months, 65% at 6 months, and 76% at 12 months. There were very few minor complications and no major complications of the surgery. These results are comparable to those of the literature that address outcomes in the adult population undergoing FESS.

CONCLUSIONS

FESS in the geriatric population is a safe and effective treatment modality for rhinosinusitis that is refractory to medical therapy. EBM rating: C.
Resorption Rate and Biocompatibility Characteristics of Two Polyester Ventilation Tubes in a Guinea Pig Model
Authors: Massey Becky L. , Wen Xuejun , Rohr L. Ralph , Tresco Patrick A. , Dahlstrom Lisa , Park Albert H.
Published: December 2004

OBJECTIVES

Determine the resorption rate and biocompatibility characteristics of 2 polyester ventilation tubes, and to determine whether soap and water exposure accelerates polyester tube degradation.

STUDY DESIGN AND SETTING

50/50 poly (D, L‐lactide‐co‐glycolide; PLGA‐50) and poly (L‐lactide; PLA) polymers were placed into the tympanic membranes of Hartley pigmented guinea pigs. Integrity of the tubes was determined by weekly otoscopic examination. Biocompatibility was assessed by comparing auditory brainstem response (ABR) thresholds and by examining tympanic membrane changes following tube resorption. Shah minigrommet ventilation tubes were used as controls. In the second portion of this study, implanted PLGA‐50 and PLA tubes were exposed weekly to a mixture of soap and water (1:5) until complete resorption was observed. Biocompatibility was assessed by periodic ABR testing and tympanic membrane examination.

RESULTS

The PLA tubes remained in the tympanic membrane for a longer period (63.2 ± 19.3 days) than the PLGA‐50 (18.8 ± 8.1 days). The tympanic membrane and resorbable tube interface demonstrated equivalent findings for auditory thresholds and tissue histopathology at the implant site compared to nonresorbable controls. The resorption behavior was not altered by exposure to soap and water. Tympanic membranes of all animals following tube degradation and soap water exposure were intact with minimal scarring and no signs of persistent foreign body response. The histological analysis showed that implantation of resorbable tubes was not accompanied by secondary infection with otorrhea through the tube, did not result in a permanent perforation or dislocation of the tube into the middle ear cavity, and was not followed by excess tympanosclerosis or localized or diffuse membrane atrophy.

CONCLUSIONS AND SIGNIFICANCE

Resorbable polyester pressure equalization tubes demonstrate predictable resorption behavior and similar bio‐compatibility characteristics when compared with nonresorbable Shah minigrommet ventilation tubes. Exposure to soap water does not accelerate polyester tube degradation nor change the host tissue response during the indwelling period or after complete resorption. The data suggests that resorbable ventilation tubes are substantially equivalent to other FDA‐approved tympanostomy devices with regard to safety and biocompatibility in the guinea pig model examined and may provide improved clinical performance by combining this approach with sustained release technology. EBM rating: B‐2.
Treatment of 125 Sinonasal Tumors: Prognostic Factors, Outcome, and Follow‐up
Authors: Blanch José L. , Ruiz Aída M. , Alos Llúcia , Traserra‐Coderch Josep , Bernal‐Sprekelsen Manuel
Published: December 2004

We reviewed our experience with sinonasal cancer patients to assess the prognostic factors. Between 1974 and 1995, we enrolled 125 patients (58 + 16 years [mean age + SD]; 94 males and 31 females). Tumor stage distribution was: T1, 64 patients; T2, 36 patients; and T3, 25 patients. Surgery as a primary treatment was selected for 106 patients (55 cases of surgery alone, 40 cases of surgery plus radiotherapy, and 11 cases of surgery plus chemotherapy with/ without radiotherapy). The 1‐, 5‐, and 10‐year overall survival was 75.0%, 37.2%, and 24.7%, respectively. The parameters with statistical prognostic significance were nodal stage, locoregional failure, and tumor stage. Histological type and primary site had no prognostic value. There were no significant survival differences between surgery alone and surgery plus radiotherapy. Sinonasal tumors have a poor survival, despite early diagnosis, radical surgical resection, and strict follow‐up. Radiotherapy seems not to be clearly necessary in stage T1.
Impaired Visual Suppression of Manually Rotated Vestibuloocular Reflex Indicates the Need of Further Evaluation by MRI and MRA in Patients with Vertigo
Authors: Shiomi Yosaku , Shiomi Yoshiko , Oda Naoharu , Fujihara Mitsuko
Published: December 2004

OBJECTIVE

MRI and MRA are accepted as valuable methods for diagnosing vertigo, although they are costly and time‐consuming. Thus, some indicator of the necessity of a detailed evaluation by MRI and MRA is desirable.

STUDY DESIGN AND SETTING

To assess the usefulness of an impairment of the visual suppression (VS) as an indicator, the relation between abnormal findings on MRI and/or MRA and impairment of the VS of manually rotated vestibuloocular reflex (VOR) was retrospectively examined in 40 consecutive patients suffering from vertigo.

RESULTS

12 of 23 patients with a low VS% were found to have a pathologic condition on MRI and/or MRA, however, no abnormality was found in any of the patients with a normal VS%. The rates of abnormality on MRI and/or MRA significantly differed between the 2 groups (X 2, P = 0.0004).

CONCLUSION

The VS% is thought to be a good indicator of the need for further evaluation by MRI and MRA in vertiginous patients.
Conventional Behind‐the‐Ear Hearing Aids after Subtotal Petrosectomy with Blind Sac Closure
Authors: McNeill Celene , Flint David , Fagan Paul
Published: December 2004

OBJECTIVE

To overcome the limitations of monaural hearing resulting from a subtotal petrosectomy and blind sac closure by fitting of a behind‐the‐ear hearing aid.

STUDY DESIGN

Three patients were fitted with aids. Patient satisfaction and the decision to buy the aids were recorded.

RESULTS

Three patients reported good hearing result despite the absence of the middle ear structures.

CONCLUSION

For patients troubled by the limitations imposed on hearing with a unilateral conductive loss following a subtotal petrosectomy and blind sac closure, a behind‐the‐ear aid is a simple and easy option to try, if the residual canal allows fitting of the aid.
The late Quaternary limnological history of Lake Kinneret (Sea of Galilee), Israel
Authors: Hazan N. , Stein M. , Agnon A. , Marco S. , Nadel D. , Negendank J.F.W. , Schwab M.J. , Neev D.
Published: December 2004

The freshwater Lake Kinneret (Sea of Galilee) and the hypersaline Dead Sea are remnant lakes, evolved from ancient water bodies that filled the tectonic depressions along the Dead Sea Transform (DST) during the Neogene–Quartenary periods. We reconstructed the limnological history (level and composition) of Lake Kinneret during the past ∼40,000 years and compared it with the history of the contemporaneous Lake Lisan from the aspect of the regional and global climate history. The lake level reconstruction was achieved through a chronological and sedimentological investigation of exposed sedimentary sections in the Kinnarot basin trenches and cores drilled at the Ohalo II archeological site. Shoreline chronology was established by radiocarbon dating of organic remains and of Melanopsis shells.

The major changes in Lake Kinneret level were synchronous with those of the southern Lake Lisan. Both lakes dropped significantly ∼42,000, ∼30,000, 23,800, and 13,000 yr ago and rose ∼39,000, 26,000, 5000, and 1600 yr ago. Between 26,000 and 24,000 yr ago, the lakes merged into a unified water body and lake level achieved its maximum stand of ∼170 m below mean sea level (m bsl). Nevertheless, the fresh and saline water properties of Lake Kinneret and Lake Lisan, respectively, have been preserved throughout the 40,000 years studied. Calcium carbonate was always deposited as calcite in Lake Kinneret and as aragonite in Lake Lisan–Dead Sea, indicating that the Dead Sea brine (which supports aragonite production) never reached or affected Lake Kinneret, even during the period of lake high stand and convergence. The synchronous level fluctuation of lakes Kinneret, Lisan, and the Holocene Dead Sea is consistent with the dominance of the Atlantic–Mediterranean rain system on the catchment of the basin and the regional hydrology. The major drops in Lake Kinneret–Lisan levels coincide with the timing of cold spells in the North Atlantic that caused a shut down of rains in the East Mediterranean and the lakes drainage area.
INTRA-ASIAN TRADE AND THE BAKUMATSU CRISIS: RECONSIDERING TOKUGAWA COMMERCIAL POLICIES IN LATE EDO PERIOD JAPAN
Authors: Hellyer Robert I.
Published: December 2004

By moving away from locating the significance of late Edo period Japanese foreign trade within the context of industrialization, this essay offers an alternative interpretation of the weakness of the Tokugawa regime and contrasting success of the Satsuma domain during the bakumatsu period crisis of the mid-nineteenth century. It argues that the marine product export trade to China provides a useful tool to understand the Tokugawa commercial strategy that focused not on “capital accumulation,” so important in the Western experience, but on supporting the economy of Nagasaki and the port's key role in the system of foreign relations. In turn it shows how Satsuma, not fettered with the same “national” goals, developed a more flexible strategy that used marine product exports to build a broad domestic and foreign trade network. With its commercial enterprises, Satsuma challenged Tokugawa commercial dominance and by implication, political authority, contributing to the larger political divisions that helped to define the bakumatsu crisis.
PUBLISHING, SOCIETY AND CULTURE IN PRE-MODERN CHINA: THE EVOLUTION OF PRINT CULTURE
Authors: Brokaw Cynthia J.
Published: December 2004

Inoue Susumu, Chūgoku shuppan bunkashi: shomotsu to chi no fūkei (A Cultural History of Chinese Publishing: Books and the Landscape of Knowledge). Nagoya: Nagoya University Press, 2002.
Eddy mixing in jet‐stream turbulence under stronger stratification
Authors: Mahalov A. , Nicolaenko B. , Tse K. L. , Joseph B.
Published: December 2004

Certain qualitative changes in turbulent eddy mixing during transitional regimes towards stronger stratification are highlighted using high‐resolution numerical simulations. The behavior of turbulent eddy mixing parameters found in this study is consistent with some recent observational results in stably stratified shear flows in the atmosphere. In particular, the flux Richardson number increases, saturates and then decreases after a critical value of the gradient Richardson number (Rig) around 2.0. Correspondingly, there is also a transition from a decreasing trend in the turbulent eddy mixing coefficient for momentum to an increasing one at the same critical Rig. The implication of the study is that such a transition can be of quite general interest in sheared flows under stronger stratification (with significant wave dynamics), and needs to be accounted for in the parameterization of microscale atmospheric turbulence.
On the radiative effects of dust on tropical convection
Authors: Stephens Graeme L. , Wood Norman B. , Pakula Lyle A.
Published: December 2004

Radiative‐convective equilibrium experiments with a two‐dimensional cloud resolving model illustrate the influence of a lofted absorbing dust layer on the organization of tropical convection. At quasi‐equilibrium, the dust‐covered region of the model exhibits increased occurrence of deep convection compared to the dust‐free region but with reduced convection in the dust‐free region controlled in part by a large‐scale monsoon‐like circulation forced by the aerosol radiative heating. The dry air associated with the dust layer inhibits convection initially over most of the dust‐covered region with convection occurring predominantly at the lateral boundaries of the layer. This behavior reproduces features which have been observed in cases of Saharan dust transport over the tropical Atlantic.
The influence of tropical instability waves on phytoplankton blooms in the wake of the Marquesas Islands during 1998 and on the currents observed during the drift of the Kon‐Tiki in 1947
Authors: Legeckis Richard , Brown Christopher W. , Bonjean Fabrice , Johnson Eric S.
Published: December 2004

During 1998, five episodes of elevated chlorophyll concentration are observed in the Pacific around the Marquesas Islands (140°W, 10°S) in SeaWiFS ocean color observations. Daily positions of geostationary satellite sea surface temperature fronts reveal the influence of the westward propagating tropical instability waves as narrow temperature fronts that extend far to the south of the equator and intersect the nutrient rich waters of the Marquesas. Because the upwelled equatorial waters are rich in iron, phytoplankton blooms are produced and are advected downstream by the South Equatorial Current. Previous studies attributed the blooms to local sources of iron and the interaction of the Marquesas with the South Equatorial Current. The satellite observations suggest that the currents that produced the phytoplankton blooms may have diverted the Kon‐Tiki southward in 1947 as described by Thor Heyerdahl.
Noncompetitive antagonism of BIBN4096BS on CGRP‐induced responses in human subcutaneous arteries
Authors: Sheykhzade Majid , Lind Henrik , Edvinsson Lars
Published: December 2004

We investigated the antagonistic effect of 1‐piperidinecarboxamide, N‐[2‐[[5amino‐l‐[[4‐(4‐pyridinyl)‐l‐piperazinyl]carbonyl]pentyl]amino]‐1‐[(3,5‐dibromo‐4‐hydroxyphenyl)methyl]‐2‐oxoethyl]‐4‐(1,4‐dihydro‐2‐oxo‐3(2H)‐quinazolinyl) (BIBN4096BS) on the calcitonin gene‐related peptide (CGRP)‐induced responses by using isometric myograph and FURA‐2 technique in human subcutaneous arteries removed in association with abdominal surgery.

BIBN4096BS, at the concentration of 1 pM, had no significant effect on the CGRP‐induced relaxation in these vessels.

At the concentration of 10 pM, BIBN4096BS had a competitive antagonistic‐like behaviour characterized by parallel rightward shift in the log CGRP concentration‐tension curve with no depression of the Emax.

At the higher concentrations (0.1 and 1 nM), BIBN4096BS had a concentration‐dependent noncompetitive antagonistic effect on the CGRP‐induced responses.

The efficacy and potency of CGRP was significantly greater in the smaller (lumen diameter ∼200 μm) human subcutaneous arteries compared to the larger ones.

The apparent agonist equilibrium dissociation constant, KA, for CGRP1 receptors in the human subcutaneous arteries was approximately 1 nM. Analysis of the relationship between receptor occupancy and response to CGRP indicates that the receptor reserve is relatively small.

Using reverse transcriptase‐polymerase chain reaction (RT‐PCR), the presence of mRNA sequences encoding the calcitonin receptor‐like receptor, receptor activity modifying protein (RAMP1, RAMP2, RAMP3) and receptor component protein were demonstrated in human subcutaneous arteries, indicating the presence of CGRP1‐like receptor and the necessary component for the receptor activation.

In conclusion, the inhibitory action of BIBN4096BS at the low concentration (10 pM) on the CGRP‐tension curve (but not intracellular calcium concentration ([Ca2+]i) resembles what is seen with a reversible competitive antagonist. However, at the higher concentrations (0.1 and 1 nM), BIBN4096BS acts as a selective noncompetitive inhibitor at CGRP1 receptors in human subcutaneous arteries.

British Journal of Pharmacology (2004) 143, 1066–1073. doi:10.1038/sj.bjp.0705967
Phosphorylation regulates the activity of the SMN complex during assembly of spliceosomal U snRNPs
Authors: Grimmler Matthias , Bauer Liane , Nousiainen Marjaana , Körner Roman , Meister Gunter , Fischer Utz
Published: December 2004

The assembly of spliceosomal U‐rich small nuclear ribonucleoproteins (U snRNPs) is an ATP‐dependent process mediated by the coordinated action of the SMN and the PRMT5 complex. Here, we provide evidence that the activity of this assembly machinery is regulated by means of post‐translational modification. We show that two main components of the SMN/PRMT5 system, namely the survival motor neuron (SMN) protein (reduced levels thereof causing spinal muscular atrophy) and pICln, are phosphorylated in vivo. Both proteins share a previously unknown motif containing either one or two phosphoserines. Alteration of these residues in SMN (serines 28 and 31) significantly impairs the activity of the SMN complex. Despite the presence of SMN in both the nucleus and cytoplasm, we find that only the latter promotes efficient SMN‐mediated U snRNP assembly activity. As cytoplasmic SMN is phosphorylated to a much larger extent, we hypothesize that this modification is a key activator of the SMN complex.
Rescue of abnormal phenotypes of the δ2 glutamate receptor‐null mice by mutant δ2 transgenes
Authors: Hirai Hirokazu , Miyazaki Taisuke , Kakegawa Wataru , Matsuda Shinji , Mishina Masayoshi , Watanabe Masahiko , Yuzaki Michisuke
Published: December 2004

The δ2 glutamate receptor (GluRδ2) has a crucial role in cerebellar functions; disruption of GluRδ2 alleles in mice (δ2−/−) impairs synapse formation and long‐term depression, which is thought to underlie motor learning in the cerebellum, and consequently leads to motor discoordination. However, it has been unclear whether GluRδ2 is activated by glutamate analogues. Here we introduced a GluRδ2 transgene, which had a mutation (Arg514Lys) in the putative ligand‐binding motif conserved in all mammalian ionotropic glutamate receptors (iGluRs) and their ancestral bacterial periplasmic amino‐acid‐binding proteins, into δ2−/− mice. Surprisingly, a mutant GluRδ2 transgene, as well as a wild‐type GluRδ2 transgene, rescued all abnormal phenotypes of δ2−/− mice. Therefore, these results indicate that the conserved arginine residue, which is crucial for the binding of iGluRs to glutamate analogues, is not essential for the restoration of GluRδ2 functions in δ2−/− mice.
Induction of peripheral lymph node addressin in human gastric mucosa infected byHelicobacter pylori
Authors: Kobayashi Motohiro , Mitoma Junya , Nakamura Naoshi , Katsuyama Tsutomu , Nakayama Jun , Fukuda Minoru
Published: December 2004

Helicobacter pyloriinfects over half the world's population and is a leading cause of peptic ulcer and gastric cancer.H. pyloriinfection results in chronic inflammation of the gastric mucosa, and progression of chronic inflammation leads to glandular atrophy and intestinal metaplasia. However, how this chronic inflammation is induced or maintained is not well known. Here, we show that chronic inflammation caused byH. pyloriinfection is highly correlated withde novosynthesis of peripheral lymph node addressin (PNAd) presented on high-endothelial venule (HEV)-like vessels. The number of HEV-like vessels dramatically increases as chronic inflammation progresses. We found that the PNAd is bound by L-selectin·IgM chimeric protein, and decorated by NCC-ST-439 antibody, which is suggested to recognize both nonsulfated and 6-sulfated sialyl Lewis X on core 2 branched O-glycans, and MECA-79 antibody, which reacts with 6-sulfoN-acetyllactosamine on extended core 1 O-glycans. These results indicate that PNAd on HEV-like vessels present in the gastric mucosa subsequent toH. pyloriinfection is similar to those on HEVs present in the secondary lymphoid organs, which are essential for lymphocyte circulation. Moreover, eradication ofH. pyloriis associated with the disappearance of HEV-like vessels in the gastric mucosa. By contrast, very few PNAd were found in the gastric mucosa of patients with chemical gastritis caused by nonsteroidal antiinflammatory drugs. These results strongly suggest that PNAd in HEV-like vessels plays a critical role in lymphocyte recruitment during chronic inflammation induced byH. pyloriinfection.
Recessive
NRL
mutations in patients with clumped pigmentary retinal degeneration and relative preservation of blue cone function
Authors: Nishiguchi Koji M. , Friedman James S. , Sandberg Michael A. , Swaroop Anand , Berson Eliot L. , Dryja Thaddeus P.
Published: December 2004

Mice lacking the transcription factor Nrl have no rod photoreceptors and an increased number of short-wavelength-sensitive cones. Missense mutations in NRL are associated with autosomal dominant retinitis pigmentosa; however, the phenotype associated with the loss of NRL function in humans has not been reported. We identified two siblings who carried two allelic mutations: a predicted null allele (L75fs) and a missense mutation (L160P) altering a highly conserved residue in the domain involved in DNA-binding-site recognition.
In vitro
luciferase reporter assays demonstrated that the NRL-L160P mutant had severely reduced transcriptional activity compared with the WT NRL protein, consistent with a severe loss of function. The affected patients had night blindness since early childhood, consistent with a severe reduction in rod function. Color vision was normal, suggesting the presence of all cone color types; nevertheless, a comparison of central visual fields evaluated with white-on-white and blue-on-yellow light stimuli was consistent with a relatively enhanced function of short-wavelength-sensitive cones in the macula. The fundi had signs of retinal degeneration (such as vascular attenuation) and clusters of large, clumped, pigment deposits in the peripheral fundus at the level of the retinal pigment epithelium (clumped pigmentary retinal degeneration). Our report presents an unusual clinical phenotype in humans with loss-of-function mutations in
NRL
.
Agonist-induced Endocytosis of CC Chemokine Receptor 5 Is Clathrin Dependent
Authors: Signoret Nathalie , Hewlett Lindsay , Wavre Silène , Pelchen-Matthews Annegret , Oppermann Martin , Marsh Mark
Published: December 2004

The signaling activity of several chemokine receptors, including CC chemokine receptor 5 (CCR5), is in part controlled by their internalization, recycling, and/or degradation. For CCR5, agonists such as the chemokine CCL5 induce internalization into early endosomes containing the transferrin receptor, a marker for clathrin-dependent endocytosis, but it has been suggested that CCR5 may also follow clathrin-independent routes of internalization. Here, we present a detailed analysis of the role of clathrin in chemokine-induced CCR5 internalization. Using CCR5-transfected cell lines, immunofluorescence, and electron microscopy, we demonstrate that CCL5 causes the rapid redistribution of scattered cell surface CCR5 into large clusters that are associated with flat clathrin lattices. Invaginated clathrin-coated pits could be seen at the edge of these lattices and, in CCL5-treated cells, these pits contain CCR5. Receptors internalized via clathrin-coated vesicles follow the clathrin-mediated endocytic pathway, and depletion of clathrin with small interfering RNAs inhibits CCL5-induced CCR5 internalization. We found no evidence for CCR5 association with caveolae during agonist-induced internalization. However, sequestration of cholesterol with filipin interferes with agonist binding to CCR5, suggesting that cholesterol and/or lipid raft domains play some role in the events required for CCR5 activation before internalization.
Reaching Migrants in Survey Research: The Use of the Global Positioning System to Reduce Coverage Bias in China
Authors: Landry Pierre F. , Shen Mingming
Published: December 2004

List-based samples are often biased because of coverage errors. The problem is especially acute in societies where the level of internal migration is high and where record keeping on the population is not reliable. We propose a solution based on spatial sampling that overcomes the inability to reach migrants in traditional area samples based on household lists. A comparison between a traditional study and our sample of Beijing demonstrates that coverage bias is greatly reduced. The successful incorporation of mobile urban residents has important substantive effects, in both univariate and multivariate analyses of public opinion data.
Molecular Bases for Sensitivity to Tubulin-Binding Herbicides in Green Foxtail
Authors: Délye Christophe , Menchari Yosra , Michel Séverine , Darmency Henri
Published: December 2004

We investigated the molecular bases for resistance to several classes of herbicides that bind tubulins in green foxtail (Setaria viridis L. Beauv.). We identified two α- and two β-tubulin genes in green foxtail. Sequence comparison between resistant and sensitive plants revealed two mutations, a leucine-to-phenylalanine change at position 136 and a threonine-to-isoleucine change at position 239, in the gene encoding α2-tubulin. Association of mutation at position 239 with herbicide resistance was demonstrated using near-isogenic lines derived from interspecific pairings between green foxtail and foxtail millet (Setaria italica L. Beauv.), and herbicide sensitivity bioassays combined with allele-specific PCR-mediated genotyping. Association of mutation at position 136 with herbicide resistance was demonstrated using herbicide sensitivity bioassays combined with allele-specific PCR-mediated genotyping. Both mutations were associated with recessive cross resistance to dinitroanilines and benzoic acids, no change in sensitivity to benzamides, and hypersensitivity to carbamates. Using three-dimensional modeling, we found that the two mutations are adjacent and located into a region involved in tubulin dimer-dimer contact. Comparison of three-dimensional α-tubulin models for organisms with contrasted sensitivity to tubulin-binding herbicides enabled us to propose that residue 253 and the vicinity of the side chain of residue 251 are critical determinants for the differences in herbicide sensitivity observed between organisms, and that positions 16, 24, 136, 239, 252, and 268 are involved in modulating sensitivity to these herbicides.
Root-to-Shoot Transport of Sulfate in Arabidopsis. Evidence for the Role of SULTR3;5 as a Component of Low-Affinity Sulfate Transport System in the Root Vasculature
Authors: Kataoka Tatsuhiko , Hayashi Naomi , Yamaya Tomoyuki , Takahashi Hideki
Published: December 2004

Xylem transport of sulfate regulates distribution of sulfur in vascular plants. Here, we describe SULTR3;5 as an essential component of the sulfate transport system that facilitates the root-to-shoot transport of sulfate in the vasculature. In Arabidopsis (Arabidopsis thaliana), SULTR3;5 was colocalized with the SULTR2;1 low-affinity sulfate transporter in xylem parenchyma and pericycle cells in roots. In a yeast (Saccharomyces cerevisiae) expression system, sulfate uptake was hardly detectable with SULTR3;5 expression alone; however, cells coexpressing both SULTR3;5 and SULTR2;1 showed substantial uptake activity that was considerably higher than with SULTR2;1 expression alone. The Vmax value of sulfate uptake activity with SULTR3;5-SULTR2;1 coexpression was approximately 3 times higher than with SULTR2;1 alone. In Arabidopsis, the root-to-shoot transport of sulfate was restricted in the sultr3;5 mutants, under conditions of high SULTR2;1 expression in the roots after sulfur limitation. These results suggested that SULTR3;5 is constitutively expressed in the root vasculature, but its function to reinforce the capacity of the SULTR2;1 low-affinity transporter is only essential when SULTR2;1 mRNA is induced by sulfur limitation. Consequently, coexpression of SULTR3;5 and SULTR2;1 provides maximum capacity of sulfate transport activity, which facilitates retrieval of apoplastic sulfate to the xylem parenchyma cells in the vasculature of Arabidopsis roots and may contribute to the root-to-shoot transport of sulfate.
Inhibition of Blue Light-Dependent H+ Pumping by Abscisic Acid through Hydrogen Peroxide-Induced Dephosphorylation of the Plasma Membrane H+-ATPase in Guard Cell Protoplasts
Authors: Zhang Xiao , Wang Hengbin , Takemiya Atsushi , Song Chun-peng , Kinoshita Toshinori , Shimazaki Ken-ichiro
Published: December 2004

Blue light (BL)-dependent H+ pumping by guard cells, which drives stomatal opening, is inhibited by abscisic acid (ABA). We investigated this response with respect to the activity of plasma membrane H+-ATPase using Vicia guard cell protoplasts. ATP hydrolysis by the plasma membrane H+-ATPase, phosphorylation of the H+-ATPase, and the binding of 14-3-3 protein to the H+-ATPase stimulated by BL were inhibited by ABA at 10 μ  m. All of these responses were similarly inhibited by hydrogen peroxide (H2O2) at 1 mm. The ABA-induced inhibitions of BL-dependent H+ pumping and phosphorylation of the H+-ATPase were partially restored by ascorbate, an intracellular H2O2 scavenger. A single-cell analysis of the cytosolic H2O2 using 2′,7′-dichlorofluorescin revealed that H2O2 was generated by ABA in guard cell protoplasts. We also indicated that H+ pumping induced by fusicoccin and the binding of 14-3-3 protein to the H+-ATPase were inhibited slightly (approximately 20%) by both ABA and H2O2. By contrast, H2O2 at 1 mm did not affect H+ pumping by the H+-ATPase in microsomal membranes. From these results, we concluded that inhibition of BL-dependent H+ pumping by ABA was due to a decrease in the phosphorylation levels of H+-ATPase and that H2O2 might be involved in this response. Moreover, there are at least two inhibition sites by ABA in the BL signaling pathway of guard cells.
Aluminum Resistance in Maize Cannot Be Solely Explained by Root Organic Acid Exudation. A Comparative Physiological Study
Authors: Piñeros Miguel A. , Shaff Jon E. , Manslank Holly S. , Carvalho Alves Vera M. , Kochian Leon V.
Published: December 2004

Root apical aluminum (Al) exclusion via Al-activated root citrate exudation is widely accepted as the main Al-resistance mechanism operating in maize (Zea mays) roots. Nonetheless, the correlation between Al resistance and this Al-exclusion mechanism has not been tested beyond a very small number of Al-resistant and Al-sensitive maize lines. In this study, we conducted a comparative study of the physiology of Al resistance using six different maize genotypes that capture the range of maize Al resistance and differ significantly in their genetic background (three Brazilian and three North American genotypes). In these maize lines, we were able to establish a clear correlation between root tip Al exclusion (based on root Al content) and Al resistance. Both Al-resistant genotypes and three of the four Al-sensitive lines exhibited a significant Al-activated citrate exudation, with no evidence for Al activation of root malate or phosphate release. There was a lack of correlation between differential Al resistance and root citrate exudation for the six maize genotypes; in fact, one of the Al-sensitive lines, Mo17, had the largest Al-activated citrate exudation of all of the maize lines. Our results indicate that although root organic acid release may play a role in maize Al resistance, it is clearly not the only or the main resistance mechanism operating in these maize roots. A number of other potential Al-resistance mechanisms were investigated, including release of other Al-chelating ligands, Al-induced alkalinization of rhizosphere pH, changes in internal levels of Al-chelating compounds in the root, and Al translocation to the shoot. However, we were unsuccessful in identifying additional Al-resistance mechanisms in maize. It is likely that a purely physiological approach may not be sufficient to identify these novel Al-resistance mechanisms in maize and this will require an interdisciplinary approach integrating genetic, molecular, and physiological investigations.
Nuclear SDH2-1 and SDH2-2 Genes, Encoding the Iron-Sulfur Subunit of Mitochondrial Complex II in Arabidopsis, Have Distinct Cell-Specific Expression Patterns and Promoter Activities
Authors: Elorza Alvaro , León Gabriel , Gómez Isabel , Mouras Armand , Holuigue Loreto , Araya Alejandro , Jordana Xavier
Published: December 2004

Three different nuclear genes encode the essential iron-sulfur subunit of mitochondrial complex II (succinate dehydrogenase) in Arabidopsis (Arabidopsis thaliana), raising interesting questions about their origin and function. To find clues about their role, we have undertaken a detailed analysis of their expression. Two genes (SDH2-1 and SDH2-2) that likely arose via a relatively recent duplication event are expressed in all organs from adult plants, whereas transcripts from the third gene (SDH2-3) were not detected. The tissue- and cell-specific expression of SDH2-1 and SDH2-2 was investigated by in situ hybridization. In flowers, both genes are regulated in a similar way. Enhanced expression was observed in floral meristems and sex organ primordia at early stages of development. As flowers develop, SDH2-1 and SDH2-2 transcripts accumulate in anthers, particularly in the tapetum, pollen mother cells, and microspores, in agreement with an essential role of mitochondria during anther development. Interestingly, in contrast to the situation in flowers, only SDH2-2 appears to be expressed at a significant level in root tips. Strong labeling was observed in all cell layers of the root meristematic zone, and a cell-specific pattern of expression was found with increasing distance from the root tip, as cells attain their differentiated state. Analysis of transgenic Arabidopsis plants carrying SDH2-1 and SDH2-2 promoters fused to the β-glucuronidase reporter gene indicate that both promoters have similar activities in flowers, driving enhanced expression in anthers and/or pollen, and that only the SDH2-2 promoter is active in root tips. These β-glucuronidase staining patterns parallel those obtained by in situ hybridization, suggesting transcriptional regulation of these genes. Progressive deletions of the promoters identified regions important for SDH2-1 expression in anthers and/or pollen and for SDH2-2 expression in anthers and/or pollen and root tips. Interestingly, regions driving enhanced expression in anthers are differently located in the two promoters.
Differential Expression on a Daily Basis of Plastid Sigma Factor Genes from the Moss Physcomitrella patens. Regulatory Interactions among PpSig5, the Circadian Clock, and Blue Light Signaling Mediated by Cryptochromes
Authors: Ichikawa Kazuhiro , Sugita Mamoru , Imaizumi Takato , Wada Masamitsu , Aoki Setsuyuki
Published: December 2004

The nuclear-encoded plastid sigma factors are supposed to be a regulatory subunit of the multisubunit bacteria-type plastid RNA polymerase. We studied here whether or not three genes, PpSig1, PpSig2, and PpSig5 encoding plastid sigma factors, are controlled by the circadian clock and/or by blue light signaling in the moss Physcomitrella patens. Among the three PpSig genes, only PpSig5 was clearly controlled by the circadian clock. In contrast to the differential regulation on a daily timescale, a pulse of blue light induced the expression of all the three PpSig genes. This induction was significantly reduced in a knockout mutant that lacked the blue light photoreceptor cryptochromes PpCRY1a and PpCRY1b, indicating that PpCRY1a and/or PpCRY1b mediate the blue light signal that induces the expression of the PpSig genes. In a daily cycle of 12-h blue light/12-h dark, the timing of peak expression of PpSig5 and a chloroplast gene psbD, encoding the D2 subunit of photosystem II, advanced in the cryptochrome mutant relative to those in the wild type, suggesting the presence of regulatory interactions among the expression of PpSig5 and psbD, the circadian clock, and the blue light signaling mediated by the cryptochrome(s).
The usual medical care for irritable bowel syndrome
Authors: Whitehead W. E. , Levy R. L. , Von Korff M. , Feld A. D. , Palsson O. S. , Turner M. , Drossman D. A.
Published: December 2004

Aims : To determine what constitutes usual medical care for irritable bowel syndrome, which patient characteristics influence choice of treatment and how satisfied patients are with care.

Methods : Patient encounters in a health maintenance organization were prospectively monitored to identify visits coded irritable bowel syndrome, abdominal pain, constipation or diarrhoea. Within 2 weeks these patients were sent postal questionnaires (n = 1770, 59% participation) to assess patient characteristics and treatment recommendations. Responders were sent follow‐up questionnaires 6 months later (77% participation) to assess adherence and satisfaction with treatment.

Results : Treatments employed most frequently were dietary advice, explanation, exercise advice, reassurance, advice to reduce stress and antispasmodic medications. Primary care physicians and gastroenterologists provided similar treatments. Patient confidence was higher for lifestyle advice (63–67, 100‐point scale) than for medications (46–59). However, adherence was greater for medications (62–79 vs. 59–69, 100‐point scale). Satisfactory relief was reported by 57%, but only 22% reported that symptom severity was reduced by half. Usual medical treatment was less effective for irritable bowel syndrome than for constipation, diarrhoea, or abdominal pain.

Conclusions : Usual medical care for irritable bowel syndrome emphasizes education and lifestyle modification more than drugs; patients have a greater expectation of benefit from lifestyle modification than drugs. Overall 57% of irritable bowel syndrome patients report satisfactory relief.
Meta‐analysis: the treatment of irritable bowel syndrome
Authors: Lesbros‐Pantoflickova D. , Michetti P. , Fried M. , Beglinger C. , Blum A. L.
Published: December 2004

To evaluate therapies available for the treatment of irritable bowel syndrome, and provide consensus recommendations for their use, a total of 51 double‐blind clinical trials using bulking agents, prokinetics, antispasmodics, alosetron, tegaserod and antidepressants were selected. The quality of studies was assessed using 5‐point scale. Meta‐analyses were performed on all studies, and on ‘high‐quality studies’. The efficacy of fibre in the global irritable bowel syndrome symptoms relief (OR: 1.9; 95% CI:1.5–2.4) was lost after exclusion of low‐quality trials (OR: 1.4; 95% CI: 1.0–2.0, P = 0.06). When excluding the low‐quality trials, an improvement of global irritable bowel syndrome symptoms with all antispasmodics (OR: 2.1; 95% CI:1.8–2.9) was maintained only for octylonium bromide, but on the basis of only two studies. Antidepressants were effective (OR: 2.6, 95% CI: 1.9–3.5), even after exclusion of low‐quality studies (OR: 1.9, 95% CI: 1.3–2.7). Alosetron (OR: 2.2; 95% CI: 1.9–2.6) and tegaserod (OR: 1.4; 95% CI: 1.2–1.5) showed a significant effect in women. We recommend the use of tegaserod for women with irritable bowel syndrome with constipation and alosetron for women with severe irritable bowel syndrome with diarrhoea. Antidepressants can be beneficial for irritable bowel syndrome with diarrhoea patients with severe symptoms. Loperamide can be recommended in painless diarrhoea. Evidence is weak to recommend the use of bulking agents in the treatment of irritable bowel syndrome with constipation.
Endoscopic ablation of Barrett's oesophagus: a randomized‐controlled trial of photodynamic therapy vs. argon plasma coagulation
Authors: Kelty C. J. , Ackroyd R. , Brown N. J. , Stephenson T. J. , Stoddard C. J. , Reed M. W. R.
Published: December 2004

Background : Barrett's oesophagus is the major risk factor for oesophageal adenocarcinoma. 5‐Aminlevulinic acid‐induced photodynamic therapy and argon plasma coagulation have been shown to be effective for ablating Barrett's oesophagus, but a comparative trial of these two modalities has not been reported.

Aims : To compare photodynamic therapy and argon plasma coagulation for the ablation of Barrett's oesophagus.

Methods : A total of 68 patients (54 male, 14 female; median age 61) with Barrett's oesophagus were randomized to photodynamic therapy (n = 34) or argon plasma coagulation (n = 34). Photodynamic therapy was performed using 5‐aminlevulinic acid (30 mg/kg) and red light. Argon plasma coagulation was administered at a power setting of 65 W. Multiple treatment sessions were performed, with follow‐up to 24 months.

Results : All patients showed a macroscopic reduction in the area of Barrett's oesophagus. This was greatest in the argon plasma coagulation group with 33 of 34 (97%) ablated, compared with 17 of 34 (50%) in the photodynamic therapy group; in the remainder, there was a reduction in the length of Barrett's oesophagus (median 50%, range: 5–90). Buried glands were found in 24% of photodynamic therapy patients, and in 21% of argon plasma coagulation patients. The median follow‐up is 12 months (range: 6–24).

Conclusions : Photodynamic therapy and argon plasma coagulation are both effective for ablating Barrett's oesophagus. Argon plasma coagulation appears more effective than photodynamic therapy, but the impact of both on carcinoma development requires larger studies with long‐term follow‐up.