bluuebunny/crossref_metadata_2025 huggingface dataset:
Mold testing by RAST and skin test methods in patients with allergic fungal sinusitis
Authors: Mabry Richard L. , Marple Bradley F. , Mabry Cynthia S.
Published: November 2005

RAST tests have traditionally been considered less sensitive than skin tests during investigation of atopy involving molds. This has been attributed to technical problems such as difficulty in binding the mold antigen to the carrier substrate. Ten patients with proven allergic fungal sinusitis were evaluated for sensitivity to 11 important molds by both RAST and dilutional intradermal testing. A predictable correlation between RAST and skin test scores was observed in many, but not all, cases. Most often this disparity was in the form of greater sensitivity indicated by skin testing than by RAST, sometimes differing by as many as 3 classes. The lack of concordance was not confined to testing for the fungi cultured from the sinuses, nor was it more or less pronounced in the case of dematiaceous fungi. The most likely causes for the disparity noted in this series are subtle differences in antigens used in skin test material and for RAST standards. Skin tests allow for evaluation of delayed and late‐phase reactions, a measurement not possible by specific IgE testing with RAST. Delayed skin test reactions were not noted in this series of patients. An additional important finding was the sensitivity of patients with allergic fungal sinusitis to virtually every fungal antigen to which they were tested.
Outcome of reflux therapy on pediatric chronic sinusitis
Authors: Bothwell Marcella R. , Parsons David S. , Talbot Andrew , Barbero Giulio J. , Wilder Barbara
Published: November 2005

OBJECTIVE

The cause of pediatric chronic sinusitis is multifactorial, but nasal edema appears to be the initial pathologic step. The objective of this study is to evaluate gastronasal reflux as a possible cause of pediatric sinusitis.

METHODS

Thirty children with chronic sinusitis were believed to be appropriate candidates for functional endoscopic sinus surgery. Children were evaluated retrospectively for their response to reflux therapy with regard to their sinus symptoms and avoidance of sinus surgery.

RESULTS

Two of the 30 children were eventually excluded because they were taken to surgery for the specific purpose of contact point release. Chart review at 24‐month follow‐up indicated that 25 of the 28 children (89%) avoided sinus surgery.

CONCLUSION

After reflux treatment, the number of children requiring sinus surgery was dramatically reduced. The results of this preliminary pediatric study indicate that gastronasal reflux should be evaluated and treated before sinus surgical intervention.
Comparison of postoperative cardiopulmonary examinations and chest radiographs to detect pulmonary complications after adult tracheotomy
Authors: Park Steven Y. , Smith Richard V.
Published: November 2005

OBJECTIVE

To prospectively evaluate the effectiveness of clinical cardiopulmonary examination compared with that of chest radiography in detecting postoperative pulmonary complications after tracheotomy in adults.

METHODS

One hundred consecutive patients undergoing tracheotomy were evaluated. Pulmonary complications were recorded, and the effectiveness of the physical examination was compared with that of the chest x‐ray in detecting these complications. Patient age, sex, diagnosis, urgency of the procedure, and anesthetic technique were evaluated to determine any relationship to postoperative complications.

RESULTS

Of the 100 patients, 87 patients underwent postoperative chest radiography, and all patients had postoperative cardiopulmonary examinations. One patient (1%) had a bilateral pneumothorax, which was detected clinically and confirmed by a chest radiograph. Five patients had postoperative pulmonary edema confirmed by clinical examination and radiography. Additional minor complications were noted, including minor bleeding and stomal infection, for an overall complication rate of 13%.

CONCLUSIONS

All postoperative pulmonary complications were detected by physical examination. Therefore routine postoperative chest radiographs in uncomplicated tracheotomies are not necessary if a thorough postoperative cardiopulmonary examination is performed. Cost analysis reveals a savings of approximately $19,000 with the proposed criteria for postoperative chest x‐ray.
Effect of topical antibiotic therapy on recovery after tonsillectomy in adults
Authors: Mann Eric A. , Blair Elizabeth A. , Levy Allen J. , Chang Audrey
Published: November 2005

OBJECTIVE

Systemic antibiotics given during the first week after tonsillectomy appear to be effective in reducing postoperative morbidity. We assessed the effectiveness of perioperative topical antibiotic rinses in reducing posttonsillectomy morbidity.

METHODS

A randomized, double‐blinded, placebo‐controlled pilot study of 36 patients undergoing tonsillectomy was used to evaluate the effects of a standard 7‐day systemic regimen of perioperative intravenous ampicillin/oral amoxicillin and 2 single‐day topical antibiotic regimens: (1) clindamycin (Cleocin) and (2) amoxicillin/clavulanate (Augmentin) and ticarcillin/clavulanate (Timentin).

RESULTS

Mean aerobic and anaerobic oral bacterial counts were decreased in both topical treatment groups compared with the placebo group on the first postoperative day, achieving statistical significance with Augmentin/Timentin (aerobic and anaerobic bacterial counts) and Cleocin (aerobic counts). Significantly less postoperative pain and mouth odor were reported for both Cleocin (P = 0.014 and P = 0.005, respectively) and Augmentin/Timentin (P = 0.026 and P = 0.05, respectively) topical treatment groups when compared with the placebo group.

CONCLUSIONS

Preliminary results indicate a reduction in oral bacterial counts and postoperative morbidity in adult patients receiving topical antibiotics compared with patients receiving placebo; further investigation is warranted.
Electrocochleographic changes after intranasal allergen challenge: A possible diagnostic tool in patients with Meniere's disease
Authors: Gibbs Scott R. , Mabry Richard L. , Roland Peter S. , Shoup Angela G. , Mabry Cynthia S.
Published: November 2005

Numerous observers have suggested a relationship between allergy and Meniere's disease, but objective proof has heretofore been limited. Using standard criteria, we studied a group of 7 patients with previously diagnosed Meniere's disease in whom significant allergy to 1 or more inhalants had also been diagnosed. Patients underwent a baseline electrocochleographic study followed by intranasal challenge with a carefully quantified amount of the allergen to which they were most sensitive. This was followed by a second electrocochleogram. Four of the 7 patients demonstrated at least a 15% increase in the summating potential/action potential ratio in 1 ear, associated with the production of subjective inner ear symptoms. We present this protocol as a potentially useful tool to further study whether inhalant allergy may be a causative factor in patients with Meniere's disease.
Early Diagnosis and Treatment of Laryngeal Injuries from Prolonged Intubation in Adults
Authors: Deeb Ziad E. , Williams Jack B. , Campbell Todd E.
Published: November 2005

Prolonged endotracheal intubation can cause injuries to 1 or more regions of the larynx, making safe extubation impossible and leading to tracheostomy in many patients. Unfortunately, a considerable number of these patients do not benefit from early laryngeal evaluation, which may reveal potentially treatable soft, obstructive tissue before it undergoes irreversible fibrosis. Between July 1992 and December 1995, we performed immediate direct telelaryngoscopy on 142 adults who required tracheostomy because of failed extubation. When present, obstructive tissue was removed with microsurgical techniques. One hundred twenty‐nine (90%) patients were decannulated within 3 weeks. The 2 main reasons for failure of early decannulation were intractable granulation (in patients with insulin‐dependent diabetes) and coexisting tracheal stenosis. Immediate telelaryngoscopy is recommended in all patients who require tracheostomy because of failed extubation. Flexible laryn‐goscopy is not adequate for thorough assessment of laryngeal damage from prolonged intubation.
Clinical‐Severity Staging System for Oral Cavity Cancer: Five‐Year Survival Rates
Authors: Pugliano Frederic A. , Piccirillo Jay F. , Zequeira Maria R. , Fredrickson John M. , Perez Carlos A. , Simpson Joseph R.
Published: November 2005

The objective of this research is to improve the classification and survival estimates for patients with oral cavity cancer by combining cancer symptom severity and comorbidity with the current TNM staging system. The study design is a retrospective medical record review that uses explicit coding criteria. The medical records of 277 patients receiving initial treatment at the Washington University Medical Center between 1980 and 1989 were reviewed. Multivariate analysis identified patient factors that significantly affected 5‐year survival. These patient factors, symptom severity and comorbidity, were combined with TNM to create a composite clinical‐severity staging system. The overall 5‐year survival rate was 46% (128/277). Survival rates by TNM stage were as follows: stage I, 72% (36/50); II, 54% (45/84); III, 37% (24/65); and IV, 29% (23/78) (χ2 = 25.27, P = 0.001). When patients were grouped according to the clinical‐severity staging system, survival rates were as follows: stage I, 77% (33/43); II, 56% (45/80); III, 42% (43/103); and IV, 14% (7/51) (χ2 = 40.62, P = 0.001). Survival estimates can be improved by adding carefully studied and suitably defined patient variables to the TNM system. The current TNM staging system for oral cavity cancer is based solely on the morphologic description of the tumor and disregards the clinical condition of the patient. Patient factors, such as cancer symptom severity and comorbidity, have a significant impact on survival. Continued exclusion of patient factors leads to imprecision in prognostic estimates and hinders interpretation of clinical studies.
Retrosigmoid‐Transmeatal en Bloc Removal of Small to Medium‐Sized Acoustic Neuromas
Authors: Colletti Vittorio , Fiorino Francesco G.
Published: November 2005

One hundred three subjects with acoustic neuroma (AN) underwent surgery—involving a retrosigmoid‐transmeatal approach—between January 1990 and December 1995. All the intracanalar tumors (n = 18) and 70 of the intra‐ and extracanalar neuromas with an extracanalar neuroma size less than 25 mm—a total of 88 patients—constituted the final study population. The first 48 patients were operated on with the use of classic procedures described in the literature, characterized by limited exposure of the internal auditory canal and removal of the tumor after debulking. Surgery in the next 40 subjects was conducted according to the technique of en bloc removal of the tumor. The main features of this technique are continuous direct recording of cochlear and facial‐nerve action potentials, wide opening of the internal auditory canal with lateral extension to the fundus, and removal of the tumor following the capsular lining without debulking. Statistical analysis of the results of the en bloc removal, compared with the previously used debulking technique, showed improvement in postoperative outcome for both auditory and facial‐nerve function.
Histologic Study of the Recurrent Laryngeal Nerve in Spasmodic Dysphonia
Authors: Kosaki Hiroko , Iwamura Shinobu , Yamazaki Ieharu
Published: November 2005

It has been reported that there were no significant changes in the recurrent laryngeal nerves of patients with adductor spasmodic dysphonia, which could explain the cause of this disease. However, the researchers who made these reports appeared to have investigated only the extralaryngeal part of the nerve involved in the neck. Because the recurrent laryngeal nerve contains many components that distribute to various organs, we must study in greater detail a more peripheral part of the motor nerve, which has a much closer relationship to vocal cord movements. At the time of surgery we obtained specimens of the thyroary‐tenoid branches of the recurrent laryngeal nerves in two female patients with adductor spasmodic dysphonia. Although histologic analysis revealed no apparent signs of either destruction or degeneration, the percentage of thin nerve fibers, the diameter of which may range from 5 to 10 μm, was higher than in normal controls. This suggests the possibility of a neurologic abnormality in the larynges of ASD patients.
Alternative to Endoscopic Sinus Surgery in the Management of Pediatric Chronic Rhinosinusitis Refractory to Oral Antimicrobial Therapy
Authors: Buchman Craig A. , Yellon Robert F. , Bluestone Charles D.
Published: November 2005

We determined the safety, feasibility, and efficacy of a treatment regimen consisting of maxillary sinus aspiration and irrigation with or without adenoidectomy, followed by culture‐directed intravenous antibiotics and oral prophylaxis, for children with chronic rhinosinusitis refractory to oral antimicrobial therapy. Twenty‐seven children (age 1–12 years, mean 6.7 years) with symptomatic (mean duration 16 months) and computed tomography‐proven sinus disease, which persisted despite at least 1 month of oral antibiotics, were treated. Twenty‐four patients (89%) had complete resolution of their presenting symptoms after intravenous therapy; in 3 (11%), intravenous therapy failed and endoscopic sinus surgery was required. Follow‐up data were available for 26 of the children (96%); 23 of them had initial complete resolution. At last follow‐up (mean 282 days, range 26–1095 days), 10 of these 23 patients (44%) remained asymptomatic, and 13 (57%) had had at least one other episode of sinusitis (mean 1.0, range 1–3) treated with oral antibiotics, with resolution. Treatment‐related complications included superficial thrombophlebitis (7%), diarrhea (7%), intravenous catheter guide‐wire kink requiring venotomy (4%), and serum sickness–like syndrome (4%). These preliminary results suggest that this treatment plan is relatively safe and feasible and that it may be a reasonable alternative to endoscopic sinus surgery in children with chronic rhinosinusitis unresponsive to orally administered antimicrobial therapy.
In Vitro Testing in Pediatric Food Allergy
Authors: HERR TIMOTHY M. , COOK PAUL R. , HIGHFILL GARY
Published: November 2005

Food allergies are an important cause of morbidity in the pediatric population. We used a questionnaire to assess the value of in vitro testing in evaluating children for food allergy. The patient population was divided into two groups: those who tested positive (Class I or greater) for food allergy (combined food/inhalant allergy or food allergy alone) and those who tested negative for food allergy (inhalant only or negative test). Although we recognize that a significant proportion of food allergies may not be IgE‐mediated, for the purposes of this study we considered a patient food allergy–positive if in vitro testing was positive and food allergy–negative if testing was negative. Thirty‐eight of 77 patients tested (49%) were positive for food allergies. Those with food allergies did not have pre‐treatment scores significantly different from those of patients negative for food allergies (55 vs. 65, p = 0.11). Similarly, we detected no statistically significant difference between the symptom‐improvement scores of the two groups (37 vs. 40, p = 0.57). We conclude that in vitro testing for food allergies is warranted in children with allergic symptoms, for several reasons: The prevalence of IgE‐mediated food allergy in children may be higher than previously thought, and children with food allergies experience the same severity of symptoms as those without. It must be remembered that in vitro testing only detects IgE levels, and therefore a negative test does not mean that the patient does not have food allergies. However, when positive, in vitro testing gives the physician the opportunity to modify the treatment plan, helping avoid time‐consuming and demanding oral food challenges. Our questionnaire also showed that food allergy and non–food allergy patients had similar pretreatment and posttreatment symptom scores.
Seasonal Patterns of Idiopathic Facial Paralysis: A 16‐Year Study
Authors: DE DIEGO JUAN I. , PRIM MARIA P. , MADERO ROSARIO , GAVIL$AAN JAVIER
Published: November 2005

The annual frequency of Bell's palsy in 16 consecutive years was investigated in a 465,000‐person health area in Madrid, Spain. The annual incidence of Bell's palsy per 100,000 population was found to be 24.1. The male‐to‐female ratio was 46:54. Seasonal difference in the incidence was noted in our series with fewer cases during summer. According to these results, the illness in Spain seems to have a similar incidence to that in Western countries. In addition to this, Bell's palsy does not have an infectious epidemiologic pattern in our country, but its frequency decreases in warm weather.
Effect of Parenteral Pentoxifylline and Topical Nitroglycerin on Skin Flap Survival
Authors: KARACAOĞLAN NACI , AKBAŞ HAYATI
Published: November 2005

Flap necrosis is still a significant complication in all types of flap surgery. The effect of parenteral pentoxifylline and nitroglycerin in improving survival of ischemic skin flaps was tested in Wistar rats. In the control group (n = 15) the mean viable length of the flaps was calculated to be 6.160 ± 0.936, and non‐necrotic flap area was found to be 1859.1 ± 269.3. In the group treated with pentoxifylline and nitro‐glycerin (n = 15), the mean viable length of the flap was calculated to be 6.907 ± 0.617, and the mean nonnecrotic flap area was found to be 2078.5 ± 172.7. In this study results showed that the use of parenteral pentoxifylline and topical nitroglycerin is effective on skin flap survival.
Microbiology of Sinusitis in Patients Undergoing Bone Marrow Transplantation
Authors: IMAMURA RUI , VOEGELS RICHARD , SPERANDIO FABIANA , SENNES LUIZ UBIRAJARA , SILVA ROBERTO , BUTUGAN OSSAMU , MINITI AROLDO
Published: November 2005

As a result of increasing use of bone marrow transplantation and new cytotoxic chemotherapy, more patients have become susceptible to sinus disease caused by unusual organisms. Sinusitis caused by fungi and gram‐negative bacteria can be difficult to treat, may lead to severe complications, and should be managed promptly in the bone marrow transplant patient. Here we present the results of 41 cultures of the paranasal sinuses obtained from 18 bone marrow transplant patients in whom sinusitis developed. The most common agents were gram‐negative bacteria (56.7%), followed by gram‐positive bacteria (26.7%) and fungi (16.6%). In 13 samples the cultures were negative. Nasal cultures were performed ipsilateral to the sinus drained in 28 cases. Concordance was obtained in only 5 (17.8%) samples. The antibiogram of the isolated agents from the maxillary sinuses in this series revealed that the most efficient antibiotics were those that covered gram‐negative bacteria. Treatment was usually prolonged in these patients, and different antibiotics were necessary to clear infections from the sinuses. In conclusion, treating sinusitis in bone marrow transplant patients may be challenging. Considerations about the microbiology and antibiogram susceptibilities of this specific population should be kept in mind when dealing with such cases.
Three‐field photometer observations of short‐period gravity wave intrinsic parameters in the 80 to 100 km height region
Authors: Reid I. M. , Woithe J. M.
Published: November 2005

A three‐field photometer (3FP) for making observations of airglow in the Mesosphere Lower Thermosphere (MLT) region has been operated at the center of the large MF aerial array located near Adelaide (138°E, 35°S) since 1993. Observations of the 557.7 nm airglow intensity emitted by atomic oxygen (OI) at heights near 97 km and the 730.0 nm airglow intensity emitted by hydroxyl (OH) near 87 km have been made simultaneously with MF spaced antenna observations of wind velocities in the 80–100 km height region. The 3FP measures the intensity of the 557.7 nm airglow in three fields separated by about 13 km at heights near 97 km, and then the intensity of the 730 nm airglow in three fields separated by about 12 km at heights near 87 km, on a 60 s cycle. These data have been analyzed to yield gravity wave observed phase speeds and horizontal wavelengths. Simultaneous MF radar data have been analyzed to yield measurements of the neutral wind velocity in 2 km height steps in the 80–100 km height interval every 2 min, and these have been used together with the observed wave parameters to calculate intrinsic gravity wave parameters. This paper presents a very brief overview of the system, the motivation for the work, and preliminary analysis of the data from 1995 until 2000.
The long wavelength topography of Beethoven and Tolstoj basins, Mercury
Authors: André Sarah L. , Watters Thomas R. , Robinson Mark S.
Published: November 2005

Topography derived from Mariner 10 stereo images is used to characterize the interior structure of two mercurian basins, Beethoven and Tolstoj. Beethoven and Tolstoj basins are shallow (∼2.5 km and ∼2 km deep, respectively) and relatively flat‐floored. Beethoven basin has an interior topographic rise near the northwest margin. The topography of Beethoven and Tolstoj basins is similar to that of lunar mare‐filled basins. Well‐developed basin‐concentric wrinkle ridges and arcuate graben associated with lunar mascons are absent in both Beethoven and Tolstoj basins. The lack of mascon tectonic features suggests that either 1) the mercurian basins have a relatively thin veneer of fill material, 2) Mercury's elastic lithosphere was too strong for significant lithospheric flexure and subsidence to occur, or 3) the basin fill material has little or no density contrast with the surrounding crust and thus exerts little net load on the mercurian lithosphere.
High atmosphere‐ocean exchange of organic carbon in the NE subtropical Atlantic
Authors: Dachs Jordi , Calleja Maria L. , Duarte Carlos M. , del Vento Sabino , Turpin Barbara , Polidori Andrea , Herndl Gerhard J. , Agustí Susana
Published: November 2005

The air‐sea exchange of organic carbon (OC) remains largely unexplored, except for few organic compounds comprising a small fraction of the total aerosol and gaseous OC in the atmosphere. Observations of high atmospheric concentrations and diffusive air‐sea exchanges for such individual organic compounds, suggest that air‐sea exchange of total OC may contribute significantly to the oceanic carbon budget. Here we quantify the atmosphere‐ocean exchanges of total OC in the NE Subtropical Atlantic. Average net gaseous diffusive air‐water fluxes averaged –31 and –25 mmol C m−2 d−1 for the spring and fall, respectively, exceeding measured OC inputs by dry aerosol deposition (FDDOC, −0.98 mmol C m−2 d−1) and net CO2 exchange (FCO2, −6.3 mmol C m−2 d−1). These fluxes are important to understand the regional carbon budget of the NE Subtropical Atlantic, and depict the atmosphere as a major dynamic vector for OC exchange with the ocean.
Simultaneous imaging of the reconnection spot in the opposite hemispheres during northward IMF
Authors: Østgaard N. , Mende S. B. , Frey H. U. , Sigwarth J. B.
Published: November 2005

Cusp aurora associated with high latitude lobe reconnection was imaged simultaneously by IMAGE and Polar in the opposite hemispheres for a short time interval on September 18, 2000. These very rare images taken during strongly northward IMF and high solar wind pressure give a unique opportunity to examine the IMF and dipole tilt control of the cusp aurora and theta aurora. As suggested by theory and observations from one hemisphere, the longitudinal location of the cusp aurora is controlled by the IMF By component, whereas the >5° poleward shift of the southern cusp aurora is attributed to the effects of the dipole tilt angle. The appearance of a non‐conjugate theta aurora can be explained by the more efficient reconnection process in the southern hemisphere due to IMF Bx > 0. Imaging of auroral signatures of magnetic reconnection also demonstrates the potential to examine differences in reconnection rate in the opposite hemispheres.
Comparison and analysis of two aerosol retrievals over the ocean in the Terra/Clouds and the Earth's Radiant Energy System–Moderate Resolution Imaging Spectroradiometer single scanner footprint data: 2. Regional evaluation
Authors: Zhao Tom X.‐P. , Laszlo Istvan , Minnis Patrick , Remer Lorraine
Published: November 2005

The advanced multichannel Moderate Resolution Imaging Spectroradiometer (MODIS) and simple independent two‐channel Advanced Very High Resolution Radiometer (AVHRR) aerosol retrieval algorithms were compared regionally using the Terra/CERES‐MODIS Single Scanner Footprint (SSF) data. On average, it was found that the two methods tend to overestimate 0.66‐μm aerosol optical thickness (AOT) compared to AERONET surface observations in the original SSF data. If the most cloud‐free data are used, the mean satellite retrievals agree to within ±10% of the AERONET data. The MODIS near‐infrared (1.60‐μm) AOTs are in better agreement with the surface data than the AVHRR‐type retrievals. The satellite‐derived aerosol size parameters are 20–30% smaller than the surface‐based values with the MODIS values closer to the AERONET values than that of AVHRR‐type. The effects of aerosol model assumptions, cloud contamination, and surface roughness on the two aerosol retrievals were analyzed in detail with the careful classification of clear‐sky and surface roughness conditions. For most of the regions examined, the annual mean AOTs from the MODIS retrieval are 0.03 and 0.02 less than their AVHRR‐type counterparts at 0.66 and 1.60 μm, respectively. However, the MODIS values may exceed the AVHRR‐type values in regions where the prevailing aerosol type varies with season or is under an apparent influence of cloud or surface disturbance. Examination of the surface treatments used by the two retrieval methods indicates the need for improvement over very rough ocean surfaces, especially for the AVHRR method. The results indicate that aerosol model assumptions become important for regional retrievals and the dynamic aerosol models used in the MODIS retrieval are better suited for simultaneously measuring the regional variations in aerosol optical properties and their global mean values.
Seasonality and stable isotopes in planktonic foraminifera off Cape Cod, Massachusetts
Authors: Keigwin Lloyd , Bice Marley , Copley Nancy
Published: November 2005

Monthly samples of stratified plankton tows taken from the slope waters off Cape Cod nearly 25 years ago are used to describe the seasonal succession of planktonic foraminifera and their oxygen isotope ratios. The 15°C seasonal cycle of sea surface temperature (SST) accounts for a diverse mixture of tropical to subpolar species. Summer samples include various Globigerinoides and Neogloboquadrina dutertrei, whereas winter and early spring species include Globigerina bulloides and Neogloboquadrina pachyderma (dextral). Globorotalia inflata lives all year but at varying water depths. Compared with the fauna in 1960–1961 (described by R. Cifelli), our samples seem warmer. Because sea surface salinity varies little during the year, δ18O is mostly a function of SST. Throughout the year, there are always species present with δ18O close to the calculated isotopic equilibrium of carbonate with surface seawater. This raises the possibility that seasonality can be estimated directly from the range of δ18O in a sediment sample provided that the δ18O‐salinity relationship is the same as today.
Late Solar Cycle Events Featured in Space Weather Week 2005
Authors: Poppe Barbara , Onsager Terrance , Murtagh William
Published: November 2005

Researchers, the airline industry, and NASA representatives met in Colorado to discuss radiation hazards, modeling capacities, and space weather's impact on space exploration initiatives.
A novel physical and functional association between nucleoside diphosphate kinase A and AMP-activated protein kinase α1 in liver and lung
Authors: Crawford Russell M. , Treharne Kate J. , Best O. Giles , Muimo Richmond , Riemen Claudia E. , Mehta Anil
Published: November 2005

Nucleoside diphosphate kinase (NDPK, NM23/awd) belongs to a multifunctional family of highly conserved proteins (∼16–20 kDa) containing two well-characterized isoforms (NM23-H1 and -H2; also known as NDPK A and B). NDPK catalyses the conversion of nucleoside diphosphates into nucleoside triphosphates, regulates a diverse array of cellular events and can act as a protein histidine kinase. AMPK (AMP-activated protein kinase) is a heterotrimeric protein complex that responds to cellular energy status by switching off ATP-consuming pathways and switching on ATP-generating pathways when ATP is limiting. AMPK was first discovered as an activity that inhibited preparations of ACC1 (acetyl-CoA carboxylase), a regulator of cellular fatty acid synthesis. We report that NM23-H1/NDPK A and AMPK α1 are associated in cytosol from two different tissue sources: rat liver and a human lung cell line (Calu-3). Co-immunoprecipitation and binding assay data from both cell types show that the H1/A (but not H2/B) isoform of NDPK is associated with AMPK complexes containing the α1 (but not α2) catalytic subunit. Manipulation of NM23-H1/NDPK A nucleotide transphosphorylation activity to generate ATP (but not GTP) enhances the activity of AMPK towards its specific peptide substrate in vitro and also regulates the phosphorylation of ACC1, an in vivo target for AMPK. Thus novel NM23-H1/NDPK A-dependent regulation of AMPK α1-mediated phosphorylation is present in mammalian cells.
Haem repression of the housekeeping 5-aminolaevulinic acid synthase gene in the hepatoma cell line LMH
Authors: Kolluri Sridevi , Sadlon Timothy J. , May Brian K. , Bonkovsky Herbert L.
Published: November 2005

Haem is essential for the health and function of nearly all cells. 5-Aminolaevulinic acid synthase-1 (ALAS-1) catalyses the first and rate-controlling step of haem biosynthesis. ALAS-1 is repressed by haem and is induced strongly by lipophilic drugs that also induce CYP (cytochrome P450) proteins. We investigated the effects on the avian ALAS-1 gene promoter of a phenobarbital-like chemical, Glut (glutethimide), and a haem synthesis inhibitor, DHA (4,6-dioxoheptanoic acid), using a reporter gene assay in transiently transfected LMH (Leghorn male hepatoma) hepatoma cells. A 9.1 kb cALAS-1 (chicken ALAS-1) promoter-luciferase-reporter construct, was poorly induced by Glut and not by DHA alone, but was synergistically induced by the combination. In contrast, a 3.5 kb promoter ALAS-1 construct was induced by Glut alone, without any further effect of DHA. In addition, exogenous haem (20 μM) repressed the basal and Glut- and DHA-induced activity of luciferase reporter constructs containing 9.1 and 6.3 kb of ALAS-1 5′-flanking region but not the construct containing the first 3.5 kb of promoter sequence. This effect of haem was subsequently shown to be dependent on the −6.3 to −3.5 kb region of the 5′-flanking region of cALAS-1 and requires the native orientation of the region. Two deletion constructs of this approx. 2.8 kb haem-repressive region (1.7 and 1.1 kb constructs) retained haem-dependent repression of basal and drug inductions, suggesting that more than one cis-acting elements are responsible for this haem-dependent repression of ALAS-1. These results demonstrate that there are regulatory regions in the 5′-flanking region of the cALAS-1 gene that respond to haem and provide a basis for further investigations of the molecular mechanisms by which haem down-regulates expression of the ALAS-1 gene.
PfPDE1, a novel cGMP-specific phosphodiesterase from the human malaria parasitePlasmodium falciparum
Authors: Yuasa Keizo , Mi-Ichi Fumika , Kobayashi Tamaki , Yamanouchi Masaya , Kotera Jun , Kita Kiyoshi , Omori Kenji
Published: November 2005

This is the first report of molecular characterization of a novel cyclic nucleotide PDE (phosphodiesterase), isolated from the human malaria parasite Plasmodium falciparum and designated PfPDE1. PfPDE1 cDNA encodes an 884-amino-acid protein, including six putative transmembrane domains in the N-terminus followed by a catalytic domain. The PfPDE1 gene is a single-copy gene consisting of two exons and a 170 bp intron. PfPDE1 transcripts were abundant in the ring form of the asexual blood stages of the parasite. The C-terminal catalytic domain of PfPDE1, produced in Escherichia coli, specifically hydrolysed cGMP with a Km value of 0.65 μM. Among the PDE inhibitors tested, a PDE5 inhibitor, zaprinast, was the most effective, having an IC50 value of 3.8 μM. The non-specific PDE inhibitors IBMX (3-isobutyl-1-methylxanthine), theophylline and the antimalarial chloroquine had IC50 values of over 100 μM. Membrane fractions prepared from P. falciparum at mixed asexual blood stages showed potent cGMP hydrolytic activity compared with cytosolic fractions. This hydrolytic activity was sensitive to zaprinast with an IC50 value of 4.1 μM, but insensitive to IBMX and theophylline. Furthermore, an in vitro antimalarial activity assay demonstrated that zaprinast inhibited the growth of the asexual blood parasites, with an ED50 value of 35 μM. The impact of cyclic nucleotide signalling on the cellular development of this parasite has previously been discussed. Thus this enzyme is suggested to be a novel potential target for the treatment of the disease malaria.
Identification, molecular cloning and functional characterization of an octaprenyl pyrophosphate synthase in intra-erythrocytic stages ofPlasmodium falciparum
Authors: Tonhosolo Renata , D'Alexandri Fabio L. , Genta Fernando A. , Wunderlich Gerhard , Gozzo Fabio C. , Eberlin Marcos N. , Peres Valnice J. , Kimura Emilia A. , Katzin Alejandro M.
Published: November 2005

Isoprenoids play important roles in all living organisms as components of structural cholesterol, steroid hormones in mammals, carotenoids in plants, and ubiquinones. Significant differences occur in the length of the isoprenic side chains of ubiquinone between different organisms, suggesting that different enzymes are involved in the synthesis of these side chains. Whereas in Plasmodium falciparum the isoprenic side chains of ubiquinone contain 7–9 isoprenic units, 10-unit side chains are found in humans. In a search for the P. falciparum enzyme responsible for the biosynthesis of isoprenic side chains attached to the benzoquinone ring of ubiquinones, we cloned and expressed a putative polyprenyl synthase. Polyclonal antibodies raised against the corresponding recombinant protein confirmed the presence of the native protein in trophozoite and schizont stages of P. falciparum. The recombinant protein, as well as P. falciparum extracts, showed an octaprenyl pyrophosphate synthase activity, with the formation of a polyisoprenoid with eight isoprenic units, as detected by reverse-phase HPLC and reverse-phase TLC, and confirmed by electrospray ionization and tandem MS analysis. The recombinant and native versions of the enzyme had similar Michaelis constants with the substrates isopentenyl pyrophosphate and farnesyl pyrophosphate. The recombinant enzyme could be competitively inhibited in the presence of the terpene nerolidol. This is the first report that directly demonstrates an octaprenyl pyrophosphate synthase activity in parasitic protozoa. Given the rather low similarity of the P. falciparum enzyme to its human counterpart, decaprenyl pyrophosphate synthase, we suggest that the identified enzyme and its recombinant version could be exploited in the screening of novel drugs.
The epididymal soluble prion protein forms a high-molecular-mass complex in association with hydrophobic proteins
Authors: Ecroyd Heath , Belghazi Maya , Dacheux Jean-Louis , Gatti Jean-Luc
Published: November 2005

We have shown previously that a ‘soluble’ form of PrP (prion protein), not associated with membranous vesicles, exists in the male reproductive fluid [Ecroyd, Sarradin, Dacheux and Gatti (2004) Biol. Reprod. 71, 993–1001]. Attempts to purify this ‘soluble’ PrP indicated that it behaves like a high-molecular-mass complex of more than 350 kDa and always co-purified with the same set of proteins. The main associated proteins were sequenced by MS and were found to match to clusterin (apolipoprotein J), BPI (bacterial permeability-increasing protein), carboxylesterase-like urinary excreted protein (cauxin), β-mannosidase and β-galactosidase. Immunoblotting and enzymatic assay confirmed the presence of clusterin and a cauxin-like protein and showed that a 17 kDa hydrophobic epididymal protein was also associated with this complex. These associated proteins were not separated by a high ionic strength treatment but were by 2-mercaptoethanol, probably due to its action on reducing disulphide bonds that maintain the interaction of components of the complex. Our results suggest that the associated PrP retains its GPI (glycosylphosphatidylinositol) anchor, in contrast with brain-derived PrP, and that it is resistant to cleavage by phosphatidylinositol-specific phospholipase C. Based on these results, the identity of the associated proteins and the overall biochemical properties of this protein ensemble, we suggest that ‘soluble’ PrP can form protein complexes that are maintained by hydrophobic interactions, in a similar manner to lipoprotein vesicles or micellar complexes.
High-resolution crystal structure of the human Notch 1 ankyrin domain
Authors: Ehebauer Matthias T. , Chirgadze Dimitri Y. , Hayward Penny , Martinez Arias Alfonso , Blundell Tom L.
Published: November 2005

The Notch receptor is part of a highly conserved signalling system of central importance to animal development. Its ANK (ankyrin) domain is required for Notch-mediated signal transduction. The crystal structure of the human Notch 1 ANK domain was solved by molecular replacement at 1.9 Å (1 Å=0.1 nm) resolution, and it shows that the features identified in the Drosophila homologue are conserved. The domain has six of the seven ANK repeats predicted from sequence. The putative first repeat, which has only part of the consensus and a long insertion, is disordered in both molecules in the asymmetric unit, possibly due to the absence of the RAM (RBPJκ-associated molecule) region N-terminal to it. The exposed hydrophobic core is involved in intermolecular interactions in the crystal. Evolutionary trace analysis identified several residues that map to the hairpins of the structure and may be of functional importance. Based on the Notch 1 ANK structure and analysis of homologous Notch ANK sequences, we predict two possible binding sites on the domain: one on the concave surface of repeat 2 and the other below the hairpins of repeats 6–7.
Characterization of the functional role of allosteric site residue Asp102 in the regulatory mechanism of human mitochondrial NAD(P)+-dependent malate dehydrogenase (malic enzyme)
Authors: Hung Hui-Chih , Kuo Meng-Wei , Chang Gu-Gang , Liu Guang-Yaw
Published: November 2005

Human mitochondrial NAD(P)+-dependent malate dehydrogenase (decarboxylating) (malic enzyme) can be specifically and allosterically activated by fumarate. X-ray crystal structures have revealed conformational changes in the enzyme in the absence and in the presence of fumarate. Previous studies have indicated that fumarate is bound to the allosteric pocket via Arg67 and Arg91. Mutation of these residues almost abolishes the activating effect of fumarate. However, these amino acid residues are conserved in some enzymes that are not activated by fumarate, suggesting that there may be additional factors controlling the activation mechanism. In the present study, we tried to delineate the detailed molecular mechanism of activation of the enzyme by fumarate. Site-directed mutagenesis was used to replace Asp102, which is one of the charged amino acids in the fumarate binding pocket and is not conserved in other decarboxylating malate dehydrogenases. In order to explore the charge effect of this residue, Asp102 was replaced by alanine, glutamate or lysine. Our experimental data clearly indicate the importance of Asp102 for activation by fumarate. Mutation of Asp102 to Ala or Lys significantly attenuated the activating effect of fumarate on the enzyme. Kinetic parameters indicate that the effect of fumarate was mainly to decrease the Km values for malate, Mg2+ and NAD+, but it did not notably elevate kcat. The apparent substrate Km values were reduced by increasing concentrations of fumarate. Furthermore, the greatest effect of fumarate activation was apparent at low malate, Mg2+ or NAD+ concentrations. The Kact values were reduced with increasing concentrations of malate, Mg2+ and NAD+. The Asp102 mutants, however, are much less sensitive to regulation by fumarate. Mutation of Asp102 leads to the desensitization of the co-operative effect between fumarate and substrates of the enzyme.
The N-terminal 26-residue fragment of human programmed cell death 5 protein can form a stable α-helix having unique electrostatic potential character
Authors: Liu Dongsheng , Yao Hongwei , Chen Yaoyao , Feng Yingang , Chen Yingyu , Wang Jinfeng
Published: November 2005

PDCD5-(1–26) is a N-terminal 26-residue fragment of human PDCD5 (programmed cell death 5) protein. PDCD5 is an important novel protein that regulates both apoptotic and non-apoptotic programmed cell death. The conformation of PDCD5 protein is a stable helical core consisting of a triple-helix bundle and two dissociated terminal regions. The N-terminal region is ordered and contains abundant secondary structure. Overexpression and purification of the N-terminal 26-residure fragment, PDCD5-(1–26), was performed in this study to better understand its tertiary structure. The spectroscopic studies using CD and hetero- and homo-nuclear NMR methods determine a stable α-helix formed by Asp3–Ala19 of PDCD5-(1–26). The N-terminal residues Asp3–Ala19 of PDCD5 were then affirmed to have the capacity to form a stable α-helix independently of the core of the protein. Analysis of the helical peptide of PDCD5-(1–26) indicates that the surface of this well-formed α-helix has a unique electrostatic potential character. This may provide an environment for the N-terminal α-helix of PDCD5 to serve as an independent functional entity of the protein. The apoptosis activity assay shows that the deletion of the N-terminal α-helix of PDCD5 significantly attenuates the apoptosis-promoting effects on HL-60 cells induced by serum withdrawal.
Phylogenetic analysis of the phytochrome superfamily reveals distinct microbial subfamilies of photoreceptors
Authors: Karniol Baruch , Wagner Jeremiah R. , Walker Joseph M. , Vierstra Richard D.
Published: November 2005

Phys (phytochromes) are a superfamily of photochromic photoreceptors that employ a bilin-type chromophore to sense red and far-red light. Although originally thought to be restricted to plants, accumulating genetic and genomic analyses now indicate that they are also prevalent among micro-organisms. By a combination of phylogenetic and biochemical studies, we have expanded the Phy superfamily and organized its members into distinct functional clades which include the phys (plant Phys), BphPs (bacteriophytochromes), Cphs (cyanobacterial Phys), Fphs (fungal Phys) and a collection of Phy-like sequences. All contain a signature GAF (cGMP phosphodiesterase/adenylate cyclase/FhlA) domain, which houses the bilin lyase activity. A PHY domain (uppercase letters are used to denote the PHY domain specifically), which helps stabilize the Pfr form (far-red-light-absorbing form of Phy), is downstream of the GAF region in all but the Phy-like sequences. The phy, Cph, BphP and Fph families also include a PLD [N-terminal PAS (Per/Arnt/Sim)-like domain] upstream of the GAF domain. Site-directed mutagenesis of conserved residues within the GAF and PLD motifs supports their importance in chromophore binding and/or spectral activity. In agreement with Lamparter, Carrascal, Michael, Martinez, Rottwinkel and Abian [(2004) Biochemistry 43, 3659–3669], a conserved cysteine within the PLD of several BphPs was found to be necessary for binding the chromophore via the C-3 vinyl side chain on the bilin A ring. Phy-type sequences were also discovered in the actinobacterium Kineococcus radiotolerans and collections of microorganisms obtained from marine and extremely acidic environments, thus expanding further the range of these photoreceptors. Based on their organization and distribution, the evolution of the Phy superfamily into distinct photoreceptor types is proposed.
Characterization of CA XV, a new GPI-anchored form of carbonic anhydrase
Authors: Hilvo Mika , Tolvanen Martti , Clark Amy , Shen Bairong , Shah Gul N. , Waheed Abdul , Halmi Piia , Hänninen Milla , Hämäläinen Jonna M. , Vihinen Mauno , Sly William S. , Parkkila Seppo
Published: November 2005

The main function of CAs (carbonic anhydrases) is to participate in the regulation of acid–base balance. Although 12 active isoenzymes of this family had already been described, analyses of genomic databases suggested that there still exists another isoenzyme, CA XV. Sequence analyses were performed to identify those species that are likely to have an active form of this enzyme. Eight species had genomic sequences encoding CA XV, in which all the amino acid residues critical for CA activity are present. However, based on the sequence data, it was apparent that CA XV has become a non-processed pseudogene in humans and chimpanzees. RT-PCR (reverse transcriptase PCR) confirmed that humans do not express CA XV. In contrast, RT-PCR and in situ hybridization performed in mice showed positive expression in the kidney, brain and testis. A prediction of the mouse CA XV structure was performed. Phylogenetic analysis showed that mouse CA XV is related to CA IV. Therefore both of these enzymes were expressed in COS-7 cells and studied in parallel experiments. The results showed that CA XV shares several properties with CA IV, i.e. it is a glycosylated glycosylphosphatidylinositol-anchored membrane protein, and it binds CA inhibitor. The catalytic activity of CA XV is low, and the correct formation of disulphide bridges is important for the activity. Both specific and non-specific chaperones increase the production of active enzyme. The results suggest that CA XV is the first member of the α-CA gene family that is expressed in several species, but not in humans and chimpanzees.
Self-assembled morphologies of monotethered polyhedral oligomeric silsesquioxane nanocubes from computer simulation
Authors: Zhang Xi , Chan Elaine R. , Glotzer Sharon C.
Published: November 2005

Self-assembly of functionalized nanoscale building blocks is a promising strategy for “bottom-up” materials design. Recent experiments have demonstrated that the self-assembly of polyhedral oligomeric silsesquioxane (POSS) “nanocubes” functionalized with organic tethers can be utilized to synthesize novel materials with highly ordered, complex nanostructures. We have performed molecular simulations for a simplified model of monotethered POSS nanocubes to investigate systematically how the parameters that control the assembly process and the resulting equilibrium structures, including concentration, temperature, tether lengths, and solvent conditions, can be manipulated to achieve useful structures via self-assembly. We report conventional lamellar and cylindrical structures that are typically found in block copolymer and surfactant systems, including a thermotropic order-order transition, but with interesting stabilization of the lamellar phase caused by the bulkiness and cubic geometry of the POSS nanocubes.
Integrable quasiclassical deformations of cubic curves
Authors: Kodama Y. , Konopelchenko B. , Alonso L. Martínez , Medina E.
Published: November 2005

A general scheme for determining and studying hydrodynamic type systems describing integrable deformations of algebraic curves is applied to cubic curves. Lagrange resolvents of the theory of cubic equations are used to derive and characterize these deformations.