bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of Docetaxel as a Second-Line Chemotherapy for Thymic Carcinoma
Authors: Oguri Tetsuya , Achiwa Hiroyuki , Kato Daisuke , Maeda Hiroyoshi , Niimi Takashi , Sato Shigeki , Ueda Ryuzo
Published: December 2004

Thymic carcinoma is a rare and aggressive tumor, and the efficacy of second-line chemotherapy is still unclear. Here, we reported a case of thymic carcinoma that responded well to the administration of docetaxel alone as a second-line chemotherapy. A 64-year-old woman was diagnosed with thymic carcinoma (squamous cell type) with bone metastasis, and she, therefore, received nedaplatin combined with etoposide and ifosfamide. She responded partially, after which she received irradiation for bone metastasis. Two months after chemotherapy, the thymic carcinoma exhibited gradual regrowth and she experienced shoulder pain. We treated this with docetaxel alone (60 mg/m2 every 4 weeks). After three courses of docetaxel, we observed a partial response and her shoulder pain disappeared. This case demonstrated that docetaxel is effective as a second-line chemotherapy for thymic carcinoma.
Phase I Trial Using Weekly Administration of Gemcitabine and Docetaxel in Patients with Advanced Pancreatic Carcinoma
Authors: Meyer F. , Lueck A. , Hribaschek A. , Lippert H. , Ridwelski K.
Published: December 2004

Background: In advanced pancreatic carcinoma, no effective chemotherapy has been found yet due to the lack of appropriate response. The frequent use of gemcitabine is based on the fact that there is a significant improvement in the quality of life, but neither an effect on remission nor a detectable increase in survival rates could be observed. Therefore, the hypothesis was that the combination of gemcitabine with other drugs can result in a better outcome of patients. The aim of this study was to determine the maximally tolerable dosage of gemcitabine and docetaxel using a weekly administration regimen. Patients and Methods: Twenty-five patients with advanced or metastatic pancreatic carcinoma received combination chemotherapy using gemcitabine and docetaxel in a weekly administration regimen, beginning with 800 mg/m2 of gemcitabine and 25 mg/m2 of docetaxel. Four patients were originally enrolled for each of the seven different dosages of both drugs. Side effects were assessed according to the WHO standard. Quality of life was evaluated according to the Core Quality of Life Questionnaire (QLQ-C30) of the European Organization for Research and Treatment of Cancer. Results: Using the two maximal dosages of gemcitabine and docetaxel (gemcitabine, 800 and 1,000 mg/m2, and docetaxel, 45 and 40 mg/m2; respectively), only 3 and 2 patients were enrolled, respectively, because of toxic side effects ≧ grade III according to WHO grading. Maximal dosages with tolerable side effects were 1,000 mg/m2 of gemcitabine and 35 mg/m2 of docetaxel given in weekly intervals. Main side effects of this combination chemotherapy were gastrointestinal symptoms and hematologic toxicity. Conclusion: Combination therapy with gemcitabine and docetaxel in advanced or metastatic pancreatic carcinoma is a well-tolerated and acceptable alternative treatment option with regard to the severity of side effects and its positive impact on quality of life and tumor-associated pain. According to the study endpoint, dosages of 1,000 mg/m2 of gemcitabine and 35 mg/m2 of docetaxel are recommended as maximum-tolerated doses (given in weekly intervals) for a future phase II trial.
Left Atrial Myxoma Prolapsing into the Left Ventricle
Authors: Karachalios G. , Bablekos G. , Karachaliou I. , Zoganas L. , Charalabopoulos A. , Charalabopoulos K.
Published: December 2004

Cardiac myxomas are rare tumors which may present differently. Left atrial myxoma is an entity from anatomopathological and clinical aspects. To the best of our knowledge, only 2 cases of infected left atrial myxomas treated surgically have been reported in the last 6 years. Herein, we present a patient with a left atrial myxoma prolapsing into the left ventricle in the diastolic phase, which was infected with Streptococcus viridans. Combined therapy, consisting of surgical management and antimicrobial therapy, was used. Clinical presentation, diagnosis and treatment are reviewed.
In vitro Antifungal Activity of Sertaconazole Compared with Nine Other Drugs against 250 Clinical Isolates of Dermatophytes and Scopulariopsis brevicaulis
Authors: Carrillo-Muñoz A.J. , Guglietta A. , Palacín C. , Casals J. , del Valle O. , Guardià C. , Rodríguez V. , Quindós G.
Published: December 2004

We have tested 250 strains belonging to 15 species of clinically important dermatophytes and Scopulariopsis against ten antifungal drugs using an agar diffusion method (NeoSensitabs™, Rosco, Taastrup, Denmark). Some of the experimental factors were adapted to dermatophyte development, such as temperature (28 vs. 35°C) and time of incubation (2–5 days vs. 21–74 h). The antifungals used are itraconazole, ketoconazole, miconazole, clotrimazole, sertaconazole, terbinafine, tioconazole, fluconazole, isoconazole and econazole. Except for fluconazole, all the drugs tested have shown to be highly effective, especially sertaconazole and terbinafine. Percentages of susceptibility ranged between 94% for terbinafine, 87.6% for sertaconazole and 86.4% clotrimazole; 81.6% econazole; 42.8% fluconazole; 57.2% isoconazole; 78.4% itraconazole; 74.4% ketoconazole; 73.3% miconazole, and 85.2% for tioconazole. Percentages of resistance were similar between sertaconazole and terbinafine (4%) but in contrast to the 48% obtained for fluconazole.
A Role for Agouti-Related Protein in Appetite Regulation in a Species with Continuous Nutrient Delivery
Authors: Wagner Christine G. , McMahon Chris D. , Marks Daniel L. , Daniel Joseph A. , Steele Barbara , Sartin James L.
Published: December 2004

Knowledge of specific neurotransmitters as well as the pathways and mechanisms regulating appetite in ruminants that continually graze, such as sheep, is incomplete. Although fundamentally agouti-related protein (AGRP) has a similar function across species to increase food intake, the regulation of AGRP may vary across grazing and intermittent feeders. To investigate the role of orexigenic peptides in the regulation of feed intake, we first extracted messenger RNA from sheep that were fasted for 3 days, which was then used for PCR followed by cloning and sequencing to demonstrate the presence of hypothalamic AGRP expression. Ovine AGRP was closely related to the bovine, but contained sequence differences with human and mouse AGRP. Analysis of genomic DNA also revealed a similar gene structure to other published species. Secondly, using dual-labeled immunohistochemistry, we determined that there was both increased AGRP immunoreactivity and increased abundance of c-Fos immunoreactivity in AGRP neurons in the arcuate nucleus of fasted sheep. Because AGRP neurons are activated by fasting, we hypothesized that AGRP would stimulate feeding in this ruminant species. Sheep fed ad libitum were injected intracerebroventricularly with concentrations of AGRP at 0.2 and 2.0 nmol/kg. AGRP at 2.0 nmol/kg significantly increased food intake at 4, 6 and 12 h (p < 0.05). A 4th study was done to investigate the interactions of AGRP and neuropeptide Y (NPY) on food intake over a 24-hour period. Intracerebroventricular injections of either AGRP or NPY significantly increased cumulative food intake over saline controls. When AGRP and NPY were injected in combination, food intake was increased over saline controls; however, AGRP did not potentiate the effects of NPY. These results demonstrate that AGRP stimulates food intake in sheep and highlights the important differences between this species and rodent models.
Rapid Neurosecretory and Cardiovascular Response to Osmotic Stimulation in Conscious Mice
Authors: Chen Hao , Morris Mariana , Key Mary P. , Chen Yanfang
Published: December 2004

Experiments were performed to evaluate the neuroendocrine and cardiovascular effects of osmotic stimulation in mice. Hypertonic saline (HS) was administered centrally or via the blood stream to conscious mice during measurement of blood pressure (BP), heart rate (HR) and plasma vasopressin (VP) and oxytocin (OT). A test of hypovolemia on VP secretion was also performed. Chronic carotid arterial cannulas were inserted for blood sampling, cardiovascular monitoring and vascular injections. Intracerebroventricular (ICV) cannulas were used for central injections. Vascular injection of HS (30 µl, 3.4 M NaCl) caused rapid and transient increases in plasma VP and OT. Plasma VP increased from 5.6 ± 0.9 to 10.0 ± 1.0 pg/ml, while plasma OT increased from 1.5 ± 0.6 to 8.6 ± 2.4 pg/ml at the earliest time point, immediately after ICV injection. ICV osmotic stimulation produced a rapid and sustained increase in plasma VP, with no change in OT. Plasma VP levels were increased from basal levels of 5.1 ± 1.5 to 13.1 ± 4.6, 11.4 ± 1.5, 12.6 ± 1.7 pg/ml at 0, 1 and 5 min after injection, respectively. ICV HS also increased plasma corticosterone. BP was increased by both vascular and central osmotic stimulation. Vascular HS increased BP immediately (Δ15.3 ± 1.7 mm Hg, 0 min) and transiently (Δ–3.9 ± 4.6 mm Hg, 5 min) while central HS produced a sustained increase in BP (Δ10 ± 1.4 and Δ9.8 ± 1.9 mm Hg, 0 and 5 min). Osmotic stimulation produced no significant changes in HR. Acute hemorrhage (∼10% decrease in blood volume) increased plasma VP (4.9 ± 1.0 vs. 8.4 ± 2.2 pg/ml). These results show the pattern of endocrine and cardiovascular responses to osmotic stimulation in conscious mice. They demonstrate that (1) there are extremely rapid changes in plasma VP and OT; (2) plasma OT is increased only after peripheral vascular hypertonic injection, and (3) central and peripheral osmotic stimulations are associated with pressor responses.
Is Epilepsy Surgery on both Hemispheres Effective?
Authors: Patil Arun Angelo , Andrews Richard V. , Johnson Matthew , Rodriguez-Sierra Jorge F.
Published: December 2004

Background: Patients with bilateral independent seizure foci are poor candidates for conventional resective epilepsy surgery. The authors have therefore used minimally invasive procedures to treat such patients. In this paper, the result of a large series of patients treated by this approach is examined to determine the effectiveness of this approach. Materials and Methods: The series had 61 patients. The range of follow-up was 15–90 months. The mean follow-up was 41.5 months with a median of 37 months. Patients’ ages at the time of surgery ranged from 3 to 54 years, with a mean of 11.3 and median of 6. Male to female ratio was 39/22. Fifty patients had complex partial seizures, 3 had Lennox-Gastaut syndrome, 4 had myotonic seizures, 2 had infantile spasm, and 2 had myoclonic seizures. Preoperative evaluation included: video electroencephalogram (EEG) monitoring using scalp electrodes, neuropsychological evaluation, magnetic resonance scans, positron emission topography and/or single photon emission computed tomography scans, magnetoencephalogram, Wada test and video EEG recording using subdural electrodes. Multiple subpial transection (MST) was the principle procedure. This procedure was supplemented (17 patients) with minimal cortical resection when intraoperative electroencephalogram indicated that an area failed to respond to MST. When an additional epileptogenic focus was present in the amygdala-hippocampus complex (5 patients), it was treated with stereotactic amygdala-hippocampotomy. The eloquent cortex was treated in 51 patients. The number of lobes treated was 2 in 5 patients, 3 in 5 patients, 4 in 10 patients, 5 in 2 patients, 6 in 38 patients and 8 in 1. Results: Seizure outcome based on Engel’s modified classification was as follows: 32 patients (52.45%) were class I, 5 (8.2%) were class II, 15 (24.59%) were class III, 3 (4.9%) were class IV and 6 (9.83%) were class V. There was no statistical difference between those who were operated on of the first half of the series and those who were operated on of the second half of the series (p = 0.1636). Similarly, there was no statistical difference between this series and two large series in which MST had been performed on one hemisphere (p values of 0.6863 and 0.7337). There was no statistical difference between those who had MST alone and those who had MST plus minimal cortical resection (p = 0.1698). There was no permanent neurological complication in this series. Conclusion: Patients with intractable epilepsy with independent seizure foci in both hemispheres can be safely treated with the approach described in this paper, and seizure control achieved by this approach is fairly satisfactory and similar to that reported in patients with surgery on one hemisphere.
The Functional Organization of the Sensorimotor Region of the Subthalamic Nucleus
Authors: Romanelli Pantaleo , Bronte-Stewart Helen , Heit Gary , Schaal David W. , Esposito Vincenzo
Published: December 2004

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is viewed by many as the ultimate therapy targeting severe advanced stages of Parkinson’s disease (PD). A fundamental constituent of the mechanisms underlying the therapeutic effects of DBS is clearly the functional organization of the STN; however, there is limited understanding of the organization of this structure in humans. Data from primates suggest that different domains can be identified in the STN, including a sensorimotor area with a segregated body map, as well as nonmotor areas. Recent clinical studies have used microelectrode recording to investigate the presence of a body map in the sensorimotor STN of PD patients. This paper will review and compare experimental and clinical data regarding the functional organization of the STN and discuss the clinical implications for PD patients undergoing STN DBS.
Associations of the UCP2 Gene Locus With Asymptomatic Carotid Atherosclerosis in Middle-Aged Women
Authors: Oberkofler H. , Iglseder B. , Klein K. , Unger J. , Haltmayer M. , Krempler F. , Paulweber B. , Patsch W.
Published: December 2004

Objective—Reactive oxygen species (ROS) contribute to atherogenesis. Uncoupling protein 2 (UCP2) reduces mitochondrial ROS generation and protects against the disease in animal models. A common −866G/A promoter polymorphism that has been associated with obesity and β-cell function may also affect UCP2 gene expression in cells of the arterial wall.

Methods and Results—Genotype distributions of the −866G/A and of a 45nt-del/ins polymorphism in the 3′-untranslated region of the UCP2 gene were determined in 1334 participants of the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR). We observed a modest association of the −866G/A promoter polymorphism and 2-loci haplotypes with asymptomatic carotid atherosclerosis in female study participants. Functional studies revealed increased expression of the −866G wild-type allele in human umbilical vein endothelial cells and differentiated THP-1 cells. Electrophoretic mobility shift assay studies and antibody-interference assays performed with nuclear extracts of various cell lines showed binding of cell-type specific protein complexes to the region encompassing the −866 site and suggested involvement of hypoxia inducible factor 1α in the regulation of UCP2 gene expression in endothelial cells and macrophages.

Conclusions—Our results suggest a role of UCP2 in atherogenesis as originally proposed from studies in animal and cell culture models.
In Vivo Expression of Recombinant Vascular Endothelial Growth Factor in Rabbit Carotid Artery Increases Production of Superoxide Anion
Authors: Suda Osamu , Smith Leslie A. , d’Uscio Livius V. , Peterson Timothy E. , Katusic Zvonimir S.
Published: December 2004

Objective—

Vascular endothelial growth factor (VEGF) is one of the most important pro-angiogenic cytokines. Ability of VEGF to stimulate formation of superoxide anion in vivo has not been studied. We hypothesized that in vivo expression of recombinant VEGF in the rabbit carotid artery increases production of superoxide anion.

Methods and Results—

Plaque-forming units (10
9
) of adenovirus-encoding human VEGF
165
(AdVEGF) or β-galactosidase (AdLacZ) were delivered into the lumen of rabbit carotid arteries. Three days after gene delivery, expression of recombinant proteins was detected in endothelium and smooth muscle cells. Endothelium-dependent relaxations to acetylcholine were impaired in AdVEGF-transduced arteries (
P
<0.01; n=5). Treatment with superoxide dismutase mimetic, Mn(III) tetra(4-benzoic acid) porphyrin chloride (10
−5
mol/L), improved relaxations to acetylcholine (
P
<0.01; n=5). Western blot analysis demonstrated increased expression of p47

phox

in AdVEGF-transduced arteries (
P
<0.05; n=8). Lucigenin chemiluminescence showed significantly higher production of superoxide anion in AdVEGF-transduced arteries (
P
<0.05; n=5 to 10).

Conclusions—

Our results suggest that in vivo expression of recombinant VEGF in the vascular endothelium increases local production of superoxide anion. Superoxide anion appears to be an important mediator of vascular effects of VEGF in vivo.
IL-18 Accelerates Atherosclerosis Accompanied by Elevation of IFN-γ and CXCL16 Expression Independently of T Cells
Authors: Tenger Charlotta , Sundborger Anna , Jawien Jacek , Zhou Xinghua
Published: December 2004

Objective—The proatherogenic effect of IL-18 is shown to be dependent on IFN-γ production. It is believed that activated T cells play a proatherogenic role through secretion of IFN-γ. However, recent studies in vitro have shown that macrophages, NK cells, and even vascular smooth muscle cells may also secrete IFN-γ after stimulation by cytokines like IL-18. We therefore investigated whether cells other than activated T cells can play a proatherogenic role via IFN-γ secretion under the stimulation of IL-18 in vivo.

Methods and Results—SCID/apoE knockout mice were injected intraperitoneally with either IL-18 or phosphate-buffered saline 3 times per week for 7 weeks. Our results show that administration of IL-18 leads to 3-fold larger lesions and 2-fold higher circulating IFN-γ despite the absence of T cells. In addition, increased IFN-γ, accompanied by elevation of the scavenger receptor/chemokine CXCL16, was observed in both lesions and spleens. Furthermore, our findings revealed that macrophages, NK cells, and vascular cells were the source of IFN-γ under the stimulation of IL-18 in the absence of T cells in vivo.

Conclusion—The current data suggest that the proatherogenic effect of IL-18 can occur in the absence of T cells and that IFN-γ secreted by macrophages, NK cells, and vascular cells is sufficient for the disease progression.
Biological Assessment of Aspirin Efficacy on Healthy Individuals
Authors: Gonzalez-Conejero Rocio , Rivera Jose , Corral Javier , Acuña Carmen , Guerrero Jose A. , Vicente Vincente
Published: December 2004

Background and Purpose—

The widespread use of aspirin requires clarification of the aspirin resistance phenomenon. Most studies on this field are focused on patients which may affect the action of aspirin.

Methods—

We evaluated the biological efficacy of aspirin in healthy subjects.

Results—

Agonist–induced platelet aggregation was fully abrogated by 100 mg of aspirin in all individuals. By contrast, with the platelet function analyzer-100 device, 33.3% of the subjects displayed no response. This failure was overcome by 500 mg or by in vitro treatment of blood with 30 μmol/L acetylsalicylic acid. Intake of 100 mg of aspirin efficiently reduced by 75% the level of 11-dehydro thromboxane B
2
(11-dTxB
2
) in all cases. However, variability on the pre-aspirin level (range 72.4 to 625.9 ng/mmol creatinine) led to substantial differences in the residual amount of the metabolite between subjects treated with aspirin (range 12.9 to 118.0 ng/mmol creatinine). Finally, there was no influence of platelet glycoprotein IIb/IIIa (Pro33Leu), platelet glycoprotein Ia/IIa, (C807T), and FXIII (Val34Leu) polymorphisms on the efficacy of aspirin. However, the cyclooxygenase (Cox)-1
50T
allele associated with higher level of 11-dTxB
2
, both before and after aspirin. Moreover, the Cox-2 −765C variant displayed a slightly higher reduction in 11-dTxB
2
level on treatment with aspirin.

Conclusions—

Our findings suggest that full resistance of healthy subjects to aspirin is rather unlikely. However, differences in aspirin absorption, or pharmacokinetic, or other unrecognized factors may lead to lack of effect of low dose of aspirin in some subjects when using tests like platelet function analyzer-100. Whether Cox polymorphisms are thrombotic risk factor for patients under aspirin will require further research.
Cardiac Troponins and N-Terminal Pro-Brain Natriuretic Peptide in Acute Ischemic Stroke Do Not Relate to Clinical Prognosis
Authors: Etgen Thorleif , Baum Hannsjoerg , Sander Kerstin , Sander Dirk
Published: December 2004

Background and Purpose—The prognostic value of cardiac troponins and natriuretic peptide in acute ischemic stroke is uncertain. We measured cardiac troponin T (cTnT), cardiac troponin I (cTnI), and N-terminal pro-brain natriuretic peptide (NT-proBNP) at admission in acute ischemic stroke patients without evident myocardial damage.

Methods—In 174 consecutive patients with MRI-confirmed ischemic stroke, serial measurements of cTnT, cTnI, and NT-proBNP were performed at 3 different time points in the hyperacute phase (at admission, on days 1 and 2). Relation of laboratory values to risk factors, stroke subtype classification, and clinical outcome after 3 months was analyzed.

Results—The highest proportion of raised parameters was found at day 2 for cTnI in 8 of 103 (7.8%), at day 3 for cTnT in 8 of 174 (4.6%), and NT-proBNP in 114 of 174 (65.5%) patients. Proportion of patients with good outcome was significantly reduced in the group with highest NT-proBNP quartile. However, using multivariate regression analysis, no significant relation to morbidity and mortality was found for cTnT, cTnI, or NT-proBNP. Significant impact on the outcome was detected for lesion size, insular involvement, sex, age, and stroke severity.

Conclusions—NT-proBNP is raised in nearly two thirds of acute stroke patients, whereas elevated cardiac troponins are found only in a small number of acute ischemic stroke patients. Neither NT-proBNP nor cardiac troponins influence clinical outcome if other risk factors are considered.
Application of Snowfall and Wind Statistics to Snow Transport Modeling for Snowdrift Control in Minnesota
Authors: Shulski Martha D. , Seeley Mark W.
Published: December 2004

Models were utilized to determine the snow accumulation season (SAS) and to quantify windblown snow for the purpose of snowdrift control for locations in Minnesota. The models require mean monthly temperature, snowfall, density of snow, and wind frequency distribution statistics. Temperature and precipitation data were obtained from local cooperative observing sites, and wind data came from Automated Surface Observing System (ASOS)/Automated Weather Observing System (AWOS) sites in the region. The temperature-based algorithm used to define the SAS reveals a geographic variability in the starting and ending dates of the season, which is determined by latitude and elevation. Mean seasonal snowfall shows a geographic distribution that is affected by topography and proximity to Lake Superior. Mean snowfall density also exhibits variability, with lower-density snow events displaced to higher-latitude positions. Seasonal wind frequencies show a strong bimodal distribution with peaks from the northwest and southeast vector direction, with an exception for locations in close proximity to the Lake Superior shoreline. In addition, for western and south-central Minnesota there is a considerably higher frequency of wind speeds above the mean snow transport threshold of 7 m s−1. As such, this area is more conducive to higher potential snow transport totals. Snow relocation coefficients in this area are in the range of 0.4–0.9, and, according to the empirical models used in this analysis, this range implies that actual snow transport is 40%–90% of the total potential in south-central and western areas of the state.
Freezing-Level Estimation with Polarimetric Radar
Authors: Brandes Edward A. , Ikeda Kyoko
Published: December 2004

A simple empirical procedure for determining freezing levels with polarimetric radar measurements is described. The algorithm takes advantage of the strong melting-layer signatures and the redundancy provided by the suite of polarimetric radar measurements—in particular, radar reflectivity, linear depolarization ratio, and cross-correlation coefficient. Freezing-level designations can be made with all volumetric scanning strategies. Application to uniform (stratiform) precipitation within 60 km of the radar and with brightband reflectivity maxima of greater than 25 dBZ suggests an accuracy of 100–200 m.
Classification and Characterization of Tropical Precipitation Based on High-Resolution Airborne Vertical Incidence Radar. Part I: Classification
Authors: Geerts Bart , Dawei Yu
Published: December 2004

Airborne measurements of vertical incidence radar reflectivity and radial velocity are analyzed for some 21 231 km of high-altitude flight tracks over tropical precipitation systems, in order to describe their characteristic vertical structure. The strength of the radar dataset lies in its superb vertical resolution, sufficient to detect unambiguously a bright band and the coincident Doppler velocity change, which identify the melting layer in stratiform precipitation. In this first of a two-part study, a technique based on the detection of this stratiform precipitation signature is developed to classify hydrometer profiles as convective, stratiform, or shallow. Even though the profiles are classified individually, stratiform and convective regions emerge, whose characteristics are described. The hydrometeor vertical velocity variability is smaller in stratiform profiles, which is consistent with the physical concept of a stratiform region. The purpose of the classification is to describe, in Part II, the composite vertical structure of the various rain types in hurricanes, as well as in isolated to organized precipitating convection sampled in Florida and Brazil.
Classification and Characterization of Tropical Precipitation Based on High-Resolution Airborne Vertical Incidence Radar. Part II: Composite Vertical Structure of Hurricanes versus Storms over Florida and the Amazon
Authors: Geerts Bart , Dawei Yu
Published: December 2004

High-resolution airborne measurements of vertical incidence radar reflectivity and Doppler velocity, as well as coincident upwelling 85-GHz radiances, are analyzed for several Atlantic Ocean hurricanes and for numerous convection-generated systems in Florida and Amazonia. Characteristic reflectivity, hydrometeor motion, and vertical air motion profiles of convective and stratiform precipitation are compared and related to their ice-scattering signature, with an emphasis on the difference between hurricanes and convection-generated storms. Hurricanes are found to be largely and clearly stratiform, displaying a remarkably narrow echo and vertical velocity spectrum. Air currents are inferred to be rising steadily at all levels, even in stratiform regions. Land-based, convection-generated stratiform regions tend to experience low-level descent and mid- to upper-level ascent, although the vertical velocity variability is large. Florida storms produce little stratiform precipitation. Their spectrum of echo and updraft strengths is broad, including some of the highest reflectivities aloft, resulting in very low 85-GHz radiances. Amazonian storms are relatively weak and are more “maritime” in echo, vertical velocity, and ice-scattering characteristics, when compared with those in Florida, especially during a westerly low-level wind regime.
Evaluating Formulations of Stable Boundary Layer Height
Authors: Vickers D. , Mahrt L.
Published: December 2004

Stable boundary layer height h is determined from eddy correlation measurements of the vertical profiles of the buoyancy flux and turbulence energy from a tower over grassland in autumn, a tower over rangeland with variable snow cover during winter, and aircraft data in the stable marine boundary layer generated by warm air advection over a cool ocean surface in summer. A well-defined h within the tower layer at the grass site (lowest 50 m) and the snow site (lowest 30 m) was definable only about 20% of the time. In the remaining stable periods, the buoyancy flux and turbulence energy either (a) remained constant with height, indicating a deep boundary layer, (b) increased with height, or (c) varied erratically with height. Approximately one-half of the tower profiles did not fit the traditional concepts of a boundary layer. The well-defined cases of h are compared with various formulations for the equilibrium depth of the stably stratified boundary layer based on the Richardson number or surface fluxes. The diagnostic models for h have limited success in explaining both the variance and mean magnitude of h at all three sites. The surface bulk Richardson number and gradient Richardson number approaches perform best for the combined data. For the surface bulk Richardson number method, the required critical value varies systematically between sites. The surface bulk Richardson number approach is modified to include a critical value that depends on the surface Rossby number, which incorporates the influence of surface roughness and wind speed on boundary layer depth.
A Revised Force–Restore Model for Land Surface Modeling
Authors: Ren Diandong , Xue Ming
Published: December 2004

To clarify the definition of the equation for the temperature toward which the soil skin temperature is restored, the prediction equations in the commonly used force–restore model for soil temperature are rederived from the heat conduction equation. The derivation led to a deep-layer temperature, commonly denoted T2, that is defined as the soil temperature at depth πd plus a transient term, where d is the e-folding damping depth of soil temperature diurnal oscillations. The corresponding prediction equation for T2 has the same form as the commonly used one except for an additional term involving the lapse rate of the “seasonal mean” soil temperature and the damping depth d. A term involving the same also appears in the skin temperature prediction equation, which also includes a transient term. In the literature, T2 was initially defined as the short-term (over several days) mean of the skin temperature, but in practice it is often used as the deep-layer temperature. Such inconsistent use can lead to drift in T2 prediction over a several-day period, as is documented in this paper. When T2 is properly defined and initialized, large drift in T2 prediction is avoided and the surface temperature prediction is usually improved. This is confirmed by four sets of experiments, each for a period during each season of 2000, that are initialized using and verified against measurements of the Oklahoma Atmospheric Surface-Layer Instrumentation System (OASIS) project.
Modeling Water and Heat Balance of the Boreal Landscape—Comparison of Forest and Arable Land in Scandinavia
Authors: Gustafsson David , Lewan Elisabet , Jansson Per-Erik
Published: December 2004

The water and heat balances of an arable field and a forest in the boreal zone in Scandinavia were explored using 3 yr of observations and simulations with two different soil–vegetation–atmosphere transfer (SVAT) models over a 30-yr period. Results from a detailed mechanistic model [coupled heat and mass transfer model (COUP)] were compared with those obtained with a large-scale type of SVAT model used in the weather prediction model at the European Centre for Medium-Range Weather Forecasts [ECMWF tiled land surface scheme (TESSEL)]. The COUP model simulations agreed well with the observations from a seasonal perspective. The TESSEL model differed significantly from the measurements when standard operational parameter values were used. The introduction of a seasonal variation in leaf-area index values, tuned canopy resistance for forest, and a reduced roughness length over snow-covered open land reduced the discrepancies. Net radiation was 40% higher in the forest when compared with the arable land, based on 30-yr simulations with both models. Furthermore, the forest was a net source of sensible heat flux, whereas the arable land was a net sink. Because of different treatment of winter interception evaporation, forest latent heat flux based on the COUP model considerably exceeded that from the TESSEL model, and suggested that the total annual evaporation was higher from the forest than from arable land. The representation of interception evaporation in winter, as well as seasonal dynamics in vegetation properties are, thus, of considerable importance for adequate simulation of forest and arable land energy fluxes within the boreal zone.
A Comparison of Gamma and Lognormal Distributions for Characterizing Satellite Rain Rates from the Tropical Rainfall Measuring Mission
Authors: Cho Hye-Kyung , Bowman Kenneth P. , North Gerald R.
Published: December 2004

This study investigates the spatial characteristics of nonzero rain rates to develop a probability density function (PDF) model of precipitation using rainfall data from the Tropical Rainfall Measuring Mission (TRMM) satellite. The minimum χ2 method is used to find a good estimator for the rain-rate distribution between the gamma and lognormal distributions, which are popularly used in the simulation of the rain-rate PDF. Results are sensitive to the choice of dynamic range, but both the gamma and lognormal distributions match well with the PDF of rainfall data. Comparison with sample means shows that the parametric mean from the lognormal distribution overestimates the sample mean, whereas the gamma distribution underestimates it. These differences are caused by the inflated tail in the lognormal distribution and the small shape parameter in the gamma distribution. If shape constraint is given, the difference between the sample mean and the parametric mean from the fitted gamma distribution decreases significantly, although the resulting χ2 values slightly increase. Of interest is that a consistent regional preference between two test functions is found. The gamma fits outperform the lognormal fits in wet regions, whereas the lognormal fits are better than the gamma fits for dry regions. Results can be improved with a specific model assumption depending on mean rain rates, but the results presented in this study can be easily applied to develop the rainfall retrieval algorithm and to find the proper statistics in the rainfall data.
A Winter Weather Index for Estimating Winter Roadway Maintenance Costs in the Midwest
Authors: Carmichael Craig G. , Gallus William A. , Temeyer Bradley R. , Bryden Mark K.
Published: December 2004

Winter roadway maintenance budget data for the state of Iowa have been combined with available climate data for a 6-yr period to create a winter weather index that provides a useful assessment of winter severity. The weather index can be combined with measures of transportation department infrastructure within a region to estimate expenses for a given time period in the region. The index was developed using artificial neural network techniques that are nonlinear and perceive patterns in the input data. Winter weather severity as diagnosed by the index correlates well with Iowa Department of Transportation roadway treatment expenses. The neural network–based index is shown to perform better than the Strategic Highway Research Program (SHRP) index and an index developed using linear regression techniques.
Reversal of long-term sepsis-induced immunosuppression by dendritic cells
Authors: Benjamim Claudia F. , Lundy Steven K. , Lukacs Nicholas W. , Hogaboam Cory M. , Kunkel Steven L.
Published: December 2004

Severe sepsis leads to long-term systemic and local immunosuppression, which is the cause of a number of complications, including pulmonary infection. A therapeutic strategy that reverses this immunosuppression is required, given the ongoing high mortality rate of patients who have survived a severe sepsis. The present study demonstrates that experimental severe sepsis renders the lung susceptible to a normally innocuous Aspergillus fumigatus fungus challenge, due to a dominant lung type 2 cytokine profile. Dendritic cells (DCs) obtained from the lungs of mice subjected to cecal ligation and puncture (CLP) model were skewed toward type 2 cytokine profile, which occurred with exaggerated expression of Toll-like receptor 2 (TLR2). The intrapulmonary transfer of bone marrow–derived DCs (BMDCs) in postseptic mice prevented fatal Aspergillus infection. This therapy reduced the overall inflammatory response and fungal growth in the lung, and promoted the balance of proinflammatory and suppressive cytokines in the lung. Thus, intrapulmonary DC supplementation appears to restore the pulmonary host response in the postseptic lung in our animal model. These data strongly suggest that lung DCs are profoundly affected as a consequence of the systemic impact of severe sepsis, and the identification of mechanisms that restore their function may serve as a key strategy to reverse sepsis-induced immunosuppression.
Tissue factor activity in whole blood
Authors: Butenas Saulius , Bouchard Beth A. , Brummel-Ziedins Kathleen E. , Parhami-Seren Behnaz , Mann Kenneth G.
Published: December 2004

Tissue factor (TF) is an integral membrane protein essential for hemostasis. During the past several years, a number of studies have suggested that physiologically active TF circulates in blood at concentrations greater than 30 pM either as a component of blood cells and microparticles or as a soluble plasma protein. In our studies using contact pathway–inhibited blood or plasma containing activated platelets, typically no clot is observed for 20 minutes in the absence of exogenous TF. An inhibitory anti-TF antibody also has no effect on the clotting time in the absence of exogenous TF. The addition of TF to whole blood at a concentration as low as 16 to 20 fM results in pronounced acceleration of clot formation. The presence of potential platelet TF activity was evaluated using ionophore-treated platelets and employing functional and immunoassays. No detectable TF activity or antigen was observed on quiescent or ionophore-stimulated platelets. Similarly, no TF antigen was detected on mononuclear cells in nonstimulated whole blood, whereas in lipopolysaccharide (LPS)–stimulated blood a significant fraction of monocytes express TF. Our data indicate that the concentration of physiologically active TF in non–cytokine-stimulated blood from healthy individuals cannot exceed and is probably lower than 20 fM.
Control of systemic B cell-mediated autoimmune disease by nonmyeloablative conditioning and major histocompatibility complex-mismatched allogeneic bone marrow transplantation
Authors: Flierman Roelof , Witteveen Hendrik J. , van der Voort Ellen I. H. , Huizinga Tom W. J. , de Vries René R. P. , Fibbe Willem E. , Toes René E. M. , van Laar Jacob M.
Published: December 2004

Systemic autoimmune disease (AID) can be controlled with conventional therapies in most patients. However, relapses are common, leading to progressive disability and premature death. Nonmyeloablative conditioning and allogeneic bone marrow transplantation (BMT) could be an effective treatment for severe AID, because of mild toxicity of the conditioning and the potential benefits of donor chimerism. We examined the effects of this treatment in experimental autoimmune arthritis. Our results demonstrate the induction of complete donor chimerism and significant suppression of disease activity. No clinical graft-versus-host disease (GVHD) was observed. The beneficial effects were most likely caused by the elimination of plasma cells producing pathogenic autoantibodies, because these antibodies disappeared rapidly after BMT. Although this type of treatment was effective in organ-specific T-cell-mediated AID, the present study provides convincing evidence that nonmyeloablative conditioning and allogeneic BMT can effectively treat severe B-cell-mediated AID with a systemic inflammatory component.
Synergy between imatinib and mycophenolic acid in inducing apoptosis in cell lines expressing Bcr-Abl
Authors: Gu Jing Jin , Santiago Lalaine , Mitchell Beverly S.
Published: December 2004

Bcr-Abl tyrosine kinase activity initiates a number of intracellular signaling cascades that result in leukemogenesis. Imatinib mesylate, a specific Bcr-Abl tyrosine kinase inhibitor, has been highly successful in the treatment of chronic myelogenous leukemia (CML). However, the emergence of imatinib resistance and the incomplete molecular response of a significant number of patients receiving this therapy have led to a search for combinations of drugs that will enhance the efficacy of imatinib. We have demonstrated that mycophenolic acid (MPA), a specific inosine monophosphate dehydrogenase (IMPDH) inhibitor that results in depletion of intracellular guanine nucleotides, is synergistic with imatinib in inducing apoptosis in Bcr-Abl-expressing cell lines. Studies of signaling pathways downstream of Bcr-Abl demonstrated that the addition of MPA to imatinib reduced the phosphorylation of both Stat5 and Lyn, a Src kinase family member. The phosphorylation of S6 ribosomal protein was also greatly reduced. These results demonstrate that inhibitors of guanine nucleotide biosynthesis may synergize with imatinib in reducing the levels of minimal residual disease in CML and lay the foundation for clinical trials in which IMPDH inhibitors are added to imatinib in patients who have suboptimal molecular responses to single agent therapy or who have progressive disease. (Blood. 2005; 105:3270-3277)
Functional analysis of pyrimidine 5′-nucleotidase mutants causing nonspherocytic hemolytic anemia
Authors: Chiarelli Laurent R. , Bianchi Paola , Fermo Elisa , Galizzi Alessandro , Iadarola Paolo , Mattevi Andrea , Zanella Alberto , Valentini Giovanna
Published: December 2004

Inherited pyrimidine 5′-nucleotidase type I (P5′N-1) deficiency is the third most common erythrocyte enzymopathy that causes hemolysis. Fourteen different mutations have been identified to date. We have investigated the molecular bases of the disease by studying the biochemical properties of the recombinant wild-type human enzyme and 4 variant proteins (D87V, L131P, N179S, and G230R) bearing missense mutations found in patients affected by nonspherocytic hemolytic anemia. P5′N-1 is a relatively stable protein and has essentially identical catalytic efficiency toward cytidine monophosphate (CMP) and uridine monophosphate (UMP). All investigated mutant proteins display impaired catalytic properties and/or reduced thermostability, providing a rationale for the pathological effects of the mutations. Despite the substantial changes in the kinetic and thermostability parameters, the enzyme activity detected in the red blood cells of patients homozygous for mutations L131P and G230R exhibits moderate alterations. This suggests that P5′N-1 deficiency is compensated, possibly by other nucleotidases or alternative pathways in nucleotide metabolism. Therefore, nucleotidase activity may not be considered a prognostic indicator in patients affected by the enzymopathy. (Blood. 2005;105:3340-3345)
Basomedial Hypothalamic Injections of Neuropeptide Y Conjugated to Saporin Selectively Disrupt Hypothalamic Controls of Food Intake
Authors: Bugarith Kishor , Dinh Thu T. , Li Ai-Jun , Speth Robert C. , Ritter Sue
Published: December 2004

Neuropeptide Y (NPY) conjugated to saporin (NPY-SAP), a ribosomal inactivating toxin, is a newly developed compound designed to selectively target and lesion NPY receptor-expressing cells. We injected NPY-SAP into the basomedial hypothalamus (BMH), just dorsal to the arcuate nucleus (ARC), to investigate its neurotoxicity and to determine whether ARC NPY neurons are required for glucoprivic feeding. We found that NPY-SAP profoundly reduced NPY Y1 receptor and αMSH immunoreactivity, as well as NPY, Agouti gene-related protein (AGRP), and cocaine and amphetamine-related transcript mRNA expression in the BMH. NPY-SAP lesions were localized to the injection site with no evidence of retrograde transport by hindbrain NPY neurons with BMH terminals. These lesions impaired responses to intracerebroventricular (icv) leptin (5 μg/5 μl·d) and ghrelin (2 μg/5 μl), which are thought to alter feeding primarily by actions on ARC NPY/AGRP and proopiomelanocortin/cocaine and amphetamine-related transcript neurons. However, the hypothesis that NPY/AGRP neurons are required downstream mediators of glucoprivic feeding was not supported. Although NPY/AGRP neurons were destroyed by NPY-SAP, the lesion did not impair either the feeding or the hyperglycemic response to 2-deoxy-d-glucose-induced blockade of glycolysis use. Similarly, responses to glucagon-like peptide-1 (GLP-1, 5 μg/3 μl icv), NPY (5 μg/3 μl icv), cholecystokinin octapeptide (4 μg/kg ip), and β-mercaptoacetate (68 mg/kg ip) were not altered by the NPY-SAP lesion. Thus, NPY-SAP destroyed NPY receptor-expressing neurons in the ARC and selectively disrupted controls of feeding dependent on those neurons but did not disrupt peptidergic or metabolic controls dependent upon circuitry outside the BMH.
Coordination of trigeminal axon navigation and patterning with tooth organ formation: epithelial-mesenchymal interactions, and epithelial Wnt4 and Tgfβ1 regulate semaphorin 3a expression in the dental mesenchyme
Authors: Kettunen Päivi , Løes Sigbjørn , Furmanek Tomasz , Fjeld Karianne , Kvinnsland Inger Hals , Behar Oded , Yagi Takeshi , Fujisawa Hajime , Vainio Seppo , Taniguchi Masahiko , Luukko Keijo
Published: December 2004

During development, trigeminal nerve fibers navigate and establish their axonal projections to the developing tooth in a highly spatiotemporally controlled manner. By analyzing Sema3a and its receptor Npn1 knockout mouse embryos, we found that Sema3a regulates dental trigeminal axon navigation and patterning, as well as the timing of the first mandibular molar innervation,and that the effects of Sema3a appear to be mediated by Npn1 present in the axons. By performing tissue recombinant experiments and analyzing the effects of signaling molecules, we found that early oral and dental epithelia, which instruct tooth formation, and epithelial Wnt4 induce Sema3aexpression in the presumptive dental mesenchyme before the arrival of the first dental nerve fibers. Later, at the bud stage, epithelial Wnt4 and Tgfβ1 regulate Sema3a expression in the dental mesenchyme. In addition, Wnt4 stimulates mesenchymal expression of Msx1transcription factor, which is essential for tooth formation, and Tgfβ1 proliferation of the dental mesenchymal cells. Thus, epithelial-mesenchymal interactions control Sema3a expression and may coordinate axon navigation and patterning with tooth formation. Moreover, our results suggest that the odontogenic epithelium possesses the instructive information to control the formation of tooth nerve supply.