bluuebunny/crossref_metadata_2025 huggingface dataset:
Parietal Representation of Symbolic and Nonsymbolic Magnitude
Authors: Fias Wim , Lammertyn Jan , Reynvoet Bert , Dupont Patrick , Orban Guy A.
Published: February 2003

The close behavioral parallels between the processing of quantitative information conveyed by symbolic and non-symbolic stimuli led to the hypothesis that there exists a common cerebral representation of quantity (Dehaene, Dehaene-Lambertz, & Cohen, 1998). The neural basis underlying the encoding of number magnitude has been localized to regions in and around the intraparietal sulcus (IPS) by brain-imaging studies. However, it has never been demonstrated that these same regions are also involved in the quantitative processing of nonsymbolic stimuli. Using functional brain imaging, we explicitly tested the hypothesis of a common substrate. Angles, lines, and two-digit numbers were presented pairwise, one to the left and one to the right of the fixation point. In the three comparison tasks, participants (n = 18) pressed the key on the side of the largest quantity. In the three control tasks, they indicated the side on which dimming occurred. A conjunction analysis between the three subtractions (comparison task-control task) revealed a site in left IPS that is specifically responsive when two stimuli have to be compared quantitatively, irrespective of stimulus format. The results confirm the hypothesis that quantity is represented by a common mechanism for both symbolic and nonsymbolic stimuli in IPS. In addition, the interaction between task and type of stimulus identified a region anterior to the conjunction site, not specific for quantitative processing, but reflecting general processes loaded by number processing.
Reading Speech from Still and Moving Faces: The Neural Substrates of Visible Speech
Authors: Calvert Gemma A. , Campbell Ruth
Published: February 2003

Speech is perceived both by ear and by eye. Unlike heard speech, some seen speech gestures can be captured in stilled image sequences. Previous studies have shown that in hearing people, natural time-varying silent seen speech can access the auditory cortex (left superior temporal regions). Using functional magnetic resonance imaging (fMRI), the present study explored the extent to which this circuitry was activated when seen speech was deprived of its time-varying characteristics.

In the scanner, hearing participants were instructed to look for a prespecified visible speech target sequence (“voo” or “ahv”) among other monosyllables. In one condition, the image sequence comprised a series of stilled key frames showing apical gestures (e.g., separate frames for “v” and “oo” [from the target] or “ee” and “m” [i.e., from nontarget syllables]). In the other condition, natural speech movement of the same overall segment duration was seen.

In contrast to a baseline condition in which the letter “V” was superimposed on a resting face, stilled speech face images generated activation in posterior cortical regions associated with the perception of biological movement, despite the lack of apparent movement in the speech image sequence. Activation was also detected in traditional speech-processing regions including the left inferior frontal (Broca's) area, left superior temporal sulcus (STS), and left supramarginal gyrus (the dorsal aspect of Wernicke's area). Stilled speech sequences also generated activation in the ventral premotor cortex and anterior inferior parietal sulcus bilaterally.

Moving faces generated significantly greater cortical activation than stilled face sequences, and in similar regions. However, a number of differences between stilled and moving speech were also observed. In the visual cortex, stilled faces generated relatively more activation in primary visual regions (V1/V2), while visual movement areas (V5/MT+) were activated to a greater extent by moving faces. Cortical regions activated more by naturally moving speaking faces included the auditory cortex (Brodmann's Areas 41/42; lateral parts of Heschl's gyrus) and the left STS and inferior frontal gyrus.

Seen speech with normal time-varying characteristics appears to have preferential access to “purely” auditory processing regions specialized for language, possibly via acquired dynamic audiovisual integration mechanisms in STS. When seen speech lacks natural time-varying characteristics, access to speech-processing systems in the left temporal lobe may be achieved predominantly via action-based speech representations, realized in the ventral premotor cortex.
Repair, Revision, and Complexity in Syntactic Analysis: An Electrophysiological Differentiation
Authors: Kaan Edith , Swaab Tamara Y.
Published: February 2003

One of the core aspects of human sentence processing is the ability to detect errors and to recover from erroneous analysis through revision of ambiguous sentences and repair of ungrammatical sentences. In the present study, we used event-related potentials (ERPs) to help identify the nature of these processes by directly comparing ERPs to complex ambiguous sentence structures with and without grammatical violations, and to simpler unambiguous sentence structures with and without grammatical violations. In ambiguous sentences, preference of syntactic analysis was manipulated such that in one condition, the structures agreed with the preferred analysis, and in another condition, a nonpreferred but syntactically correct analysis (garden path) was imposed. Nonpreferred ambiguous structures require revision, whereas ungrammatical structures require repair. We found that distinct ERPs reflected different characteristics of syntactic processing. Specifically, our results are consistent with the idea that a positivity with a posterior distribution across the scalp (posterior P600) is an index of syntactic processing difficulty, including repair and revision, and that a frontally distributed positivity (frontal P600) is related to ambiguity resolution and/ or to an increase in discourse level complexity.
Simplicius on the Meaning of Sentences: A Commentary on In Cat. 396,30-397,28
Authors: Gaskin
Published: February 2003

At Categories 12b5-16 Aristotle appears to regard the referents of declarative sentences, such as "Socrates is sitting," as what later writers were to call complexe significabilia, i.e., items such as that Socrates is sitting. Simplicius' discussion of this passage in his commentary on the Categories clearly shows the influence of Stoic philosophy of language; but, if we follow the text printed by Kalbfleisch, Simplicius' commentary is seen to be a muddle of Stoic and Aristotelian elements, neither properly understood. It is possible, however, by making a crucial emendation to the text, to preserve the Aristotelian integrity of Simplicius' theory of meaning. On that line Simplicius would be adopting the view that a declarative sentence refers to a thought in the first instance and a complexe significabile in the second instance. This view is plausibly the upshot of combining the Categories text with the first chapter of De Interpretatione.
FEMALE MATE PREFERENCE IS FOR MALE TOTAL LENGTH, NOT TAIL LENGTH IN FERAL GUPPIES
Authors: Karino Kenji , Matsunaga Jun
Published: February 2003

Exaggerated male traits can evolve either directly by female choice of males with those traits or indirectly by female preferences for related traits. In this study, we tested whether female choice was based upon male tail length or total length in a feral guppy population in Okinawa, Japan. In this population, about 30% of the males had elongated sword-like tails, and even swordless males had longer tails than females. A series of dichotomous female choice experiments revealed that female guppies chose mates by total length, not by tail length itself. This is inconsistent with the handicap principle. Tail elongation of male guppies may have evolved as a male mating strategy to enhance their attraction to females, mediated by female preference for longer male total length. However, only one-third of the males developed pronounced sword-like tails. This suggests that there are some costs for tail elongation or trade-offs between multiple sexually selected traits. Alternatively, tail elongation may be a deceptive male strategy with frequency-dependent success.
Partial liquid ventilation with small volumes of FC 3280 increases survival time in experimental ARDS
Authors: Kaisers U , Max M , Walter J , Kuhlen R , Pappert D , Falke K , Rossaint R
Published: February 2003

The aim of this study was to determine the prolonged effects of sequential doses of a highly purified perfluorocarbon (FC 3280) on gas exchange and survival time in experimental acute respiratory distress syndrome (ARDS). The study was prospective, randomized and controlled. Twelve pigs (body weight 30 +/- 5 (mean +/- SD) kg) were surfactant-depleted by repetitive lung lavages, reducing arterial oxygen tension (Pa,O2) to 6.9 +/- 1.6 kPa (52 +/- 12 mmHg) (mean +/- SD) at an inspired oxygen fraction (Fi,O2) of 1.0. They were then randomized to receive partial liquid ventilation by sequential intratracheal application of 7.5 mL.kg-1 FC 3280 at 30 min intervals to a cumulative dose of 15 mL.kg-1 (treatment group), or to receive no further treatment (control group). Haemodynamics and gas exchange were assessed at 30 min intervals after instillation, and hourly afterwards in both groups until death. In the treatment group, Pa,O2 was 8.9 +/- 4.4 kPa (67 +/- 33 mmHg) after 7.5 mL.kg-1 FC 3280 and 14.1 +/- 9.9 kPa (106 +/- 74 mmHg) after 15 mL.kg-1 FC 3280 (NS). In the control group, gas exchange remained unchanged. Haemodynamics were stable in the treatment group and deteriorated in the control group. Peak airway pressures and dynamic compliance were not significantly affected in the treatment group. Mean survival time was 8.2 +/- 4.5 h in the treatment group and 1.8 +/- 1.4 h in the control group (p < 0.05). Upon histological examination, both study groups were not significantly different in total lung injury scores. We conclude that partial liquid ventilation with small volumes of FC 3280 provides improvement in gas exchange and increases survival time in experimental acute respiratory distress syndrome.
Effects of N-acetylcysteine on tissue oxygenation in patients with multiple organ failure and evidence of tissue hypoxia
Authors: Agusti AG , Togores B , Ibanez J , Raurich JM , Maimo A , Bergada J , Marse P , Jorda R
Published: February 2003

Covert tissue hypoxia, particularly of the splanchnic region, appears important in the pathogenesis of multiple organ failure (MOF). This investigation evaluates the effects of N-acetylcysteine (NAC) upon several measures of tissue oxygenation in 10 patients with severe MOF and evidence of splanchnic hypoxia (as suggested by a pathologically low value (< 7.32) of the pH of the gastric mucosa (pHi)). Patients were studied following a prospective, randomized, placebo-controlled, cross-over design. Measurements included pulmonary and systemic haemodynamics, cardiac output by thermodilution, arterial and mixed venous blood gas values, blood lactate concentration, whole-body oxygen uptake by analysis of the expired gases, and pHi by tonometry. A complete set of measurements was obtained before and 45 min after the infusion of NAC (150 mg.kg-1 in 250 mL of saline) and, also, before and 45 min after the infusion of an equivalent volume of saline. NAC increased the cardiac index and vasodilated the systemic circulation (p < 0.01). However, O2 delivery to the tissues did not increase because the arterial oxygen content fell after NAC (p < 0.01). Mean O2 extraction or lactate concentration did not change after NAC, and pHi fell slightly (from 7.11 +/- 0.21 to 7.07 +/- 0.21; p < 0.05). The infusion of saline did not modify any variable significantly. The O2 extraction fraction increased exponentially in those patients with reduced O2 transport to the tissues. These results argue against a beneficial effect of N-acetylcysteine upon tissue oxygenation in patients with severe multiple organ failure and evidence of splanchnic hypoxia. Furthermore, they suggest that the mechanisms controlling the extraction of oxygen by the peripheral tissues in these patients were not impaired.
Determinants of effective ventilation during nasal intermittent positive pressure ventilation
Authors: Parreira VF , Jounieaux V , Delguste P , Aubert G , Dury M , Rodenstein DO
Published: February 2003

Our aim was to verify in healthy subjects submitted to nasal intermittent positive pressure ventilation (nIPPV) with a volumetric ventilator on controlled mode, whether changes in ventilator settings (delivered tidal volume (VT), respiratory frequency (fR) and inspiratory flow (V'I) could influence effective minute ventilation (V'E), thus allowing identification of the settings resulting in the highest V'E during nIPPV. We then compared these experimentally obtained "best" settings to those obtained retrospectively in a group of patients submitted to long-term nIPPV for clinical reasons. We studied 10 healthy subjects awake and asleep, and 33 patients with restrictive ventilatory disorders. Changes in delivered V'I (for a constant delivered VT and fR) led to significant changes in V'E. V'E was significantly higher when a given delivered V'E was obtained using higher fR and lower VT than when it was obtained using lower delivered fR and higher VT. Increases in fR generally resulted in increases in V'E. The "best" settings derived from these results were: VT: 13 mL.kg-1 of body weight; fR: 20 breaths.min-1 and V'I: 0.56-0.85 L.s-1. The corresponding average values found in the patient group were: delivered VT: 14 mL.kg-1; fR: 23 breaths.min-1 and delivered V'I: 0.51 L.s-1. Changes in minute ventilation resulting from modifications in ventilator settings can be attributed to the glottic response to mechanical influences. This leads to "ideal" settings quite different from the standard ones in intubated patients. Values derived from nasal intermittent positive pressure ventilation in healthy subjects seem to apply to patients submitted to long-term nasal intermittent positive pressure ventilation.
Pulmonary surfactant in cystic fibrosis
Authors: Griese M , Birrer P , Demirsoy A
Published: February 2003

Cystic fibrosis (CF) leads to a chronic inflammation of the airways with significant air flow limitations developing early in the course of the disease. As a well-functioning pulmonary surfactant is necessary to keep the alveoli and the small conducting airways open during expiration, we hypothesized that the biochemical and biophysical properties of surfactant may be impaired in CF. Bronchoalveolar lavage fluid obtained during a clinically stable period was analysed from 20 CF patients (5.9-20 yrs) and 17 healthy children and adults. CF patients had significantly elevated total and polymorphonuclear neutrophil cell counts, whereas the concentrations of total protein and phospholipids did not differ from controls. The percentage of surface active phospholipids, phosphatidylcholine and phosphatidylglycerol, and the concentration of surfactant protein A were significantly reduced in CF patients. Surfactant protein B was unchanged. Although the relative proportion of large aggregates was higher in CF, their surface active properties were inferior, as assessed in the pulsating bubble surfactometer. Because the capacity of CF lavage fractions to inhibit surfactant function was the same as that of controls, impaired minimal surface tension was more likely to be due to the biochemical alterations detected, than to inhibition of a well-functioning surfactant. The impaired pulmonary surfactant system in clinically stable patients with cystic fibrosis is in agreement with the view that surfactant dysfunction may contribute to lung disease in cystic fibrosis.
Nebulization of a bovine surfactant in cystic fibrosis: a pilot study
Authors: Griese M , Bufler P , Teller J , Reinhardt D
Published: February 2003

Cystic fibrosis (CF) is a lethal disorder which results in excessive airway secretions and in chronic inflammation of the airways. In vitro and in vivo studies have shown that a lack of surfactant results in the closure of the small airways. In this pilot study, we aimed to determine whether surfactant administered by aerosol might improve lung function on a short-term basis in patients with CF. In a randomized, crossover double-blind pilot study, 120 mg of a lipid-extracted bovine surfactant (Alveofact) or placebo was aerosolized to five young adult patients with CF over a period of 30 min for five consecutive days. The sample size had the power of 90% to detect an increase in forced expiratory volume in one second (FEV1) of 15% (p < 0.05). Jet nebulization of surfactant produced particles of which more than 75% were the respirable range (< 5 microns). The inhalations were well tolerated. No changes in serum antibody titres against the surfactant proteins-B and -C (SP-B/SP-C) were observed. No differences in FEV1 and forced vital capacity were found before, and 30 or 90 min after, the inhalation. This pilot study shows no acute or short-term benefits of surfactant inhalation in young adults with cystic fibrosis. However, a beneficial effect of exogenous surfactant cannot be excluded before other reasons for a lack of effect, such as insufficient quantity delivered, inhomogeneous distribution or inhibition of the surfactant in the lungs, have been completely ruled out.
Nocturnal ventilatory support in patients with cystic fibrosis: comparison with supplemental oxygen
Authors: Gozal D
Published: February 2003

Progressive deterioration of lung function in cystic fibrosis (CF) patients may lead to significant hypoxaemia and hypercapnia, especially during sleep. The effects of bi-level noninvasive positive pressure nasal mask ventilation (NIPPV) on respiration and sleep were compared to those of low-flow oxygen therapy in six CF patients (mean +/- SD age 22.3 +/- 4.7 yrs, with severe lung disease (forced expiratory volume in one second (FEV1) 29.4 +/- 3.4% predicted). Compared to the control night, NIPPV and oxygen therapy significantly improved overall night-time oxygen saturation during both rapid eye movement (REM) and non-rapid eye movement (NREM) sleep stages. However, significant increases in transcutaneous CO2 tension occurred during oxygen therapy, while NIPPV markedly improved alveolar ventilation during all sleep states. Sleep architecture and arousals remained unchanged during NIPPV and oxygen therapy treatment nights. We conclude that noninvasive positive pressure ventilation improves sleep-related hypoxaemia and hypercapnia in severe cystic fibrosis patients without affecting sleep. The long-term compliance and benefits of noninvasive positive pressure ventilation remain unclear.
Internal consistency reliability and predictive validity of a modified N. Huang clinical scoring system in adult cystic fibrosis patients
Authors: Matouk E , Ghezzo RH , Gruber J , Hidvegi R , Gray-Donald K
Published: February 2003

We described a modified N. Huang scoring system and its application as a measure of disease status and progression in a population of adult cystic fibrosis patients. We evaluated the scoring for internal consistency reliability and predictive validity. We applied the scoring system to 109 adult cystic fibrosis patients followed at the Montreal Chest Institute. Complete data were available on 36 deceased patients. The total score represented the sum of the clinical, radiological and pulmonary function subscores, minus the complications subscore. It ranged between 0 (worst health) and 100 points (best health). The total score showed a high degree of internal consistency and reliability with an estimated Cronbach coefficient alpha of 0.934. Both total score and forced expiratory volume in one second (FEV1) percentage predicted were significant predictors of survival at 36 and 24 months. However, there was a progressive decrease in the discriminating power of FEV1 percentage pred for predicting survival at 24, 18, 12 and 6 months. The total score showed a progressive and consistent pattern clearly predicting the outcome. A total score < 41, < 38, < 35 and < 30 points was associated with a poor prognosis for survival at 24, 18, 12, and 6 months, respectively. The clinical and complications subscores were the most discriminating components of the total score. The total score of the modified N. Huang scoring system offered a better discriminating scale, as compared to forced expiratory volume in one second % predicted, in the prognostic evaluation of end-stage cystic fibrosis patients. It could be of value in decisions for lung transplantation in these patients.
Maximal work capacity in relation to nutritional status in children with cystic fibrosis
Authors: Gulmans VA , de Meer K , Brackel HJ , Helders PJ
Published: February 2003

In children with cystic fibrosis, objective parameters of exercise tolerance are needed which are easy to measure in nonspecialized centres. We investigated maximal workload (W'max) in children with cystic fibrosis in relation to body weight and fat-free mass, and compared this with results for maximal oxygen consumption (V'O2,max). Fourteen patients with cystic fibrosis performed an incremental maximal exercise test on a bicycle ergometer. W'max, V'O2,max, body weight and fat-free mass were measured. W'max and V'O2,max were significantly correlated (r = 0.91; p < 0.001). Using standard deviation scores in relation to reference values, W'max and V'O2,max per kilogram body weight were significantly higher than uncorrected W'max and V'O2,max (mean difference (95% CI) 0.63 (0.24-1.01) and 0.91 (0.32-1.49) SD units, respectively). There was no such difference after correction for fat-free mass. Standardized V'O2,max was significantly higher than standardized W'max (mean difference (95% CI): 1.59 (1.14-2.04)), also after correction for body weight and fat-free mass. In children with mild-to-moderate cystic fibrosis, maximal workload per kilogram fat-free mass, but not per kilogram body weight, is a useful parameter to correct for diminished nutritional status. In these patients, maximal workload is consistently lower than maximal oxygen consumption. Taking into account this difference, maximal workload and maximal workload per kilogram fat-free mass can be used for follow-up of paediatric patients with cystic fibrosis in nonspecialized settings.
Albumin is not suitable as a marker of bronchoalveolar lavage dilution in interstitial lung disease
Authors: Ward C , Fenwick J , Booth H , Walters EH
Published: February 2003

We have investigated the origin of raised bronchoalveolar lavage (BAL) albumin levels in interstitial lung diseases (ILDs), and the hypothesis that acute flux during BAL might contribute to the elevated levels of albumin in samples from ILD patients. Total albumin concentrations were measured in three separately aspirated 60 mL aliquots of BAL in 12 ILD patients and seven control subjects, and previous work indicating that BAL albumin levels may be raised in ILD was confirmed. In addition, the extent of acute flux from the circulation was investigated using 1.48 MBq of 125I-radiolabelled human serum albumin injected intravenously shortly before the procedure. It was found that acute albumin flux occurred in only a minority of the ILD patients (4 out of 12) and control subjects (3 out of 7). These results indicate that the elevated levels of plasma proteins, such as albumin, documented in BAL aspirates from ILD patients are not an artefact of the BAL procedure related to increased vascular permeability, and that this finding is more likely to be related to the effects of chronic inflammatory changes in the lung due to the underlying disease. The work confirms that albumin is unsuitable as a denominator for the normalization of bronchoalveolar lavage solute results, since levels can vary, both as a result of acute flux and, more frequently, because of disease activity.
Cytokine mRNA gene expression in active and nonactive pulmonary sarcoidosis
Authors: Minshall EM , Tsicopoulos A , Yasruel Z , Wallaert B , Akoum H , Vorng H , Tonnel AB , Hamid Q
Published: February 2003

Sarcoidosis is a multisystem granulomatous disease associated with the expansion and activation of CD4+ T-lymphocytes and macrophages. To investigate the immunopathology of active and nonactive pulmonary sarcoidosis, we have examined the expression of cytokine gene transcripts in bronchoalveolar lavage cells from 15 patients with active pulmonary sarcoidosis, eight patients with non-active pulmonary sarcoidosis, and nine normal controls. Using in situ hybridization, the percentage of cells expressing messenger ribonucleic acid (mRNA) for interleukin (IL)-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, IL-12 and interferon-gamma (IFN-gamma) were compared in the groups studied. In individuals with active sarcoidosis, there were significantly greater proportions of cells expressing mRNA for IL-2, IL-10, IL-12 and IFN-gamma than in subjects with nonactive disease and normal controls (p < 0.01). There was no significant difference in the percentage of positive cells expressing IL-10 and IL-12 mRNA in the nonactive group compared to the normal controls (p > 0.05). No significant differences in the percentages of IL-3, IL-4 and IL-5 mRNA positive cells were observed between active and nonactive sarcoidosis patients and normal controls (p > 0.05). These results demonstrate that there is a preferential expression of T-helper type 1 cytokines in pulmonary sarcoidosis, and that cytokines related to macrophage activation are the most prominent. In addition, these data implicate an elevated expression of interleukin-2, -10 and -12 and interferon-gamma in active compared to nonactive sarcoidosis.
The efficacy of pulmonary thromboendarterectomy on long-term gas exchange
Authors: Tanabe N , Okada O , Nakagawa Y , Masuda M , Kato K , Nakajima N , Kuriyama T
Published: February 2003

It has not been delineated in detail how pulmonary thromboendarterectomy (PTE) affects gas exchange through long-term follow-up. In Japan, this surgery has been undertaken in a limited number of institutions, and the results of PTE have not been well publicized. A total of 25 patients were operated on during the period from 1985 to 1996 at our institution, and the overall mortality rate was 16%. Our criteria for PTE were based on the following: 1) thrombi surgically accessible as judged by angiographic study; 2) mean pulmonary arterial pressure > or = 30 mmHg. The efficacies of PTE were analysed on haemodynamics as well as gas exchange at one month postsurgery and during follow-up (6-24 months). Significant haemodynamic improvement was obtained as early as 1 month after surgery. Improvement of gas exchange lagged, but was then observed during follow-up, and the improvement level of pulmonary haemodynamics was sustained. The early postoperative restrictive impairment and ventilation-perfusion abnormality on lung perfusion scan resolved during the follow-up period. It was concluded that the early postoperative efficacy of pulmonary throm-boendarterectomy was mainly achieved due to the reduction of pulmonary hypertension, whereas improvement in gas exchange was obtained over the longer term.
Co-stimulation of cultured peripheral blood mononuclear cells from intrinsic asthmatics with exogenous recombinant IL-6 produce high levels of IL-4-dependent IgE
Authors: Sanchez-Guerrero IM , Herrero N , Muro M , Vegara RP , Campos M , Garcia-Alonso AM , Alvarez MR
Published: February 2003

Asthma is an inflammatory airway disorder, traditionally subdivided into extrinsic, immunoglobulin E (IgE)-mediated, and intrinsic asthma of unknown aetiology. IgE synthesis requires contact between T- and B-cells and a signal provided by interleukin (IL)-4, which can be modulated by IL-6. The objective of this study was to evaluate the effects of IL-4 and IL-6 on total IgE synthesis by peripheral blood mononuclear cells from intrinsic and extrinsic asthmatics. Peripheral blood mononuclear cells from intrinsic and extrinsic asthmatic patients and from healthy subjects were cultured and stimulated with pokeweed mitogen, recombinant IL-4 and IL-6. The IgE level in serum and supernatants was measured by an enzyme-linked immunoassay. Serum IgE was significantly lower in intrinsic asthma than in extrinsic asthma, but significantly higher than in control subjects. IgE production by cultured mononuclear cells from extrinsic asthmatics was not modified after exogenous IL-4 and IL-6 addition. However, intrinsic asthmatics showed enhancement of IgE synthesis in response to IL-4 stimulation, reaching a threefold increase of the spontaneous IgE values, when simultaneous recombinant IL-4 plus IL-6 stimulus was used. Our results indicate that exogenous recombinant interleukin-6 can significantly upregulate the interleukin-4-dependent immunoglobulin E synthesis in intrinsic asthma. This suggests that immunoglobulin E could also play a role in the pathogenesis of intrinsic asthma, in which an interleukin-6 threshold would be critical.
Bone mineral density in asthmatic patients treated with inhaled corticosteroids: a case-control study
Authors: Luengo M , del Rio L , Pons F , Picado C
Published: February 2003

Recent studies suggest that inhaled corticosteroids can adversely affect bone metabolism. The objective of this study was to evaluate the importance of these adverse effects in a case-control study. Bone mineral density (BMD) was measured in 48 asthmatic adults (15 males and 33 females) treated with inhaled steroids (beclomethasone or budesonide) and in 48 gender and age-matched healthy subjects at baseline and at 2 yrs. Vertebral BMD was measured by dual energy X-ray densitometry. Patients had been treated with a dose of 662 +/- 278 micrograms (range 300-1,000 micrograms) of beclomethasone dipropionate or budesonide for more than 1 yr (mean duration of treatment 10.6 yrs, range 1-16 yrs). Twenty four patients had needed 1-6 short courses of oral steroids and seven had received oral corticosteroids (mean daily dose 6.2 mg prednisone) for 2-15 yrs more than 4 yrs prior to the BMD measurements. During the follow-up, 14 patients required 1-3 short courses of oral steroids. There was no correlation either between inhaled corticosteroid doses or duration of treatment and BMD values. There were no significant differences in BMD baseline values between patients and healthy controls. BMD significantly decreased in both groups at 2 yrs, from 1.08 +/- 0.19 to 1.05 +/- 0.19 g.cm-2 (p = 0.002) in asthmatics versus 1.12 +/- 0.17 to 1.09 +/- 0.18 g.cm-2 (p = 0.008) in controls. There were no significant differences in BMD loss between patients and healthy controls. Furthermore, no differences were found in bone loss when pre- and postmenopausal women were compared with their healthy control counterparts. No differences in baseline BMD were found between patients who had received regular oral corticosteroid therapy or booster courses of oral corticosteroids and those who had not. Inhaled corticosteroid treatment at a mean dose of 662 micrograms.day-1 and sporadic booster courses of oral corticosteroids do not further increase bone mass loss with respect to that expected from natural bone mass loss.
Comparative loss of activity of recombinant secretory leukoprotease inhibitor and alpha 1-protease inhibitor caused by different forms of oxidative stress
Authors: Vogelmeier C , Biedermann T , Maier K , Mazur G , Behr J , Krombach F , Buhl R
Published: February 2003

Secretory leukoprotease inhibitor (SLPI) and alpha 1-protease inhibitor (alpha 1-PI) are powerful antiproteases currently under investigation for their potential to protect the lung from neutrophil elastase (NE). The aim of this study was to determine whether the recombinant form of SLPI (rSLPI) and alpha 1-PI show different grades of loss of inhibitory activity when exposed to reactive oxygen metabolites. We incubated rSLPI and alpha 1-PI with N-chlorosuccinimide (NCS), chloramines, activated polymorphonuclear leucocytes (PMNs) and activated alveolar macrophages (AMs). Under all conditions evaluated, both antiproteases were partially inactivated. The resulting anti-NE activity of rSLPI was not significantly different from that of alpha 1-PI after exposure to NCS (p > 0.5), chloramines (p > 0.6), activated PMNs (p > 0.07) and activated AMs (p > 0.9). In conclusion, recombinant secretory leukoprotease inhibitor and alpha 1-protease inhibitor lose antineutrophil elastase activity to a similar extent when exposed to conditions that may be present in inflammatory lung disorders.
Effects of cigarette smoking on the serum concentration of lung surfactant protein A (SP-A)
Authors: Kida K , Oda H , Yamano Y , Kagawa J
Published: February 2003

We have tested the hypothesis that serum surfactant protein A (SP-A) production may be affected by cigarette smoke exposure, and that alterations in serum levels may reflect smoking habits. A total of 52 subjects were divided into the following two groups: active smokers (Group A; n = 23); and nonsmokers (Group B; n = 29). The assessment of smoking habit was determined by self-report, carbon monoxide concentration in expired air, and cotinine concentration in urine. Serum SP-A was compared in both groups and was found to be higher in Group A (active smokers) (p < 0.002). We conclude that surfactant protein A levels are increased in the serum of smokers. However, it was found that this is not a sensitive discriminating factor to separate smokers from nonsmokers.
Cross-bridge kinetics in respiratory muscles
Authors: Sieck GC , Prakash YS
Published: February 2003

In respiratory muscles, force generation and shortening depend on the cyclical interaction of actin and myosin (cross-bridge cycling). During cross-bridge cycling, adenosine triphosphate (ATP) is hydrolysed. The globular head region of the myosin heavy chain (MyHC) possesses both the binding site to actin and the site for ATP hydrolysis. Therefore, the MyHC is both a structural and enzymatic protein. Different isoforms of MyHC are expressed in skeletal muscle fibres, and these MyHC isoforms provide mechanical and metabolic diversity. In the present study, the relationships between MyHC isoform expression in single rat diaphragm muscle fibres and their mechanical and energetic properties were evaluated. The expression of MyHC isoforms in single diaphragm muscle fibres was identified using electrophoretic and immunohistochemical techniques. Cross-bridge cycling kinetics in diaphragm muscle fibres clearly depend on MyHC isoform expression, and these differences are interpreted in the context of Huxley's two-state cross-bridge model. It is concluded that the unique mechanical and energetic properties of myosin heavy chain isoforms are designed to accomplish different motor behaviours of the diaphragm muscle, and that, as a result of these unique properties, a selective recruitment of diaphragm muscle fibres is essential to avoid fatigue.
Recurrent respiratory distress associated with carbamazepine overdose
Authors: Wilschut FA , Cobben NA , Thunnissen FB , Lamers RJ , Wouters EF , Drent M
Published: February 2003

Acute interstitial pneumonia or diffuse alveolar damage is uncommon as an adverse reaction to carbamazepine therapy. We report the case of a 36 yr old woman, who developed respiratory failure after auto-intoxication with carbamazepine. Analysis, including bronchoalveolar lavage and lung tissue biopsy, suggested diffuse alveolar damage due to carbamazepine.
Treatment of Localized Nonorbital, Nonparameningeal Head and Neck Rhabdomyosarcoma: Lessons Learned From Intergroup Rhabdomyosarcoma Studies III and IV
Authors: Pappo Alberto S. , Meza Jane L. , Donaldson Sarah S. , Wharam Moody D. , Wiener Eugene S. , Qualman Stephen J. , Maurer Harold M. , Crist William M.
Published: February 2003

Purpose: The characteristics and clinical outcomes of children and adolescents with localized nonorbital, nonparameningeal head and neck rhabdomyosarcoma (RMS) treated on national protocols from the Intergroup Rhabdomyosarcoma Group are reported.

Patients and Methods: We conducted a retrospective review of 164 children and adolescents enrolled in the third and fourth Intergroup Rhabdomyosarcoma Studies. Variables analyzed included age, sex, primary tumor site, histologic subtype, clinical group, therapy, site and rate of treatment failure, and time to initial recurrence.

Results: Localized nonorbital, nonparameningeal RMS accounted for 9% of all cases of RMS. The median age at diagnosis was 5 years; the median follow-up was 6.6 years. Estimated 5-year failure-free survival (FFS) and survival (S) rates were 76% (95% CI, 69% to 83%) and 83% (95% CI, 77% to 89%), respectively. In multivariate analysis, patients with clinically involved regional nodes (N1) had worse FFS (P = .02). For patients with embryonal tumors, FFS was significantly improved, especially among patients with Group I/II without nodal disease clinical Group I, II N0. For patients with alveolar/undifferentiated histology, FFS was significantly worse in children under the age of 1 year. Actuarial estimates of recurrences at 15 years were local (19%), regional (5%), and distant (9%).

Conclusion: More than 80% of patients with RMS of the head and neck are cured of their disease using surgery and vincristine, dactinomycin ± cyclophosphamide with or without radiotherapy. Our results indicate that early, limited exposure to cyclophosphamide might reduce recurrence in low-risk embryonal patients and that reduced dosages might achieve comparable results with improved toxicity profiles. These hypotheses will be tested in the next generation of trials from the Soft Tissue Committee of the Children’s Oncology Group.
c-Jun N-Terminal Kinase Activation of Activator Protein-1 Underlies Homologous Regulation of the Gonadotropin-Releasing Hormone Receptor Gene in αT3-1 Cells
Authors: Ellsworth Buffy S. , White Brett R. , Burns Ann T. , Cherrington Brian D. , Otis Annette M. , Clay Colin M.
Published: February 2003

Reproductive function is dependent on the interaction between GnRH and its cognate receptor found on gonadotrope cells of the anterior pituitary gland. GnRH activation of the GnRH receptor (GnRHR) is a potent stimulus for increased expression of multiple genes including the gene encoding the GnRHR itself. Thus, homologous regulation of the GnRHR is an important mechanism underlying gonadotrope sensitivity to GnRH. Previously, we have found that GnRH induction of GnRHR gene expression in αT3-1 cells is partially mediated by protein kinase C activation of a canonical activator protein-1 (AP-1) element. In contrast, protein kinase A and a cAMP response element-like element have been implicated in mediating the GnRH response of the GnRHR gene using a heterologous cell model (GGH3). Herein we find that selective removal of the canonical AP-1 site leads to a loss of GnRH regulation of the GnRHR promoter in transgenic mice. Thus, an intact AP-1 element is necessary for GnRH responsiveness of the GnRHR gene both in vitro and in vivo. Based on in vitro analyses, GnRH appeared to enhance the interaction of JunD, FosB, and c-Fos at the GnRHR AP-1 element. Although enhanced binding of cFos reflected an increase in gene expression, GnRH appeared to regulate both FosB and JunD at a posttranslational level. Neither overexpression of a constitutively active Raf-kinase nor pharmacological blockade of GnRH-induced ERK activation eliminated the GnRH response of the GnRHR promoter. GnRH responsiveness was, however, lost in αT3-1 cells that stably express a dominant-negative c-Jun N-terminal kinase (JNK) kinase, suggesting a critical role for JNK in mediating GnRH regulation of the GnRHR gene. Consistent with this possibility, we find that the ability of forskolin and membrane-permeable forms of cAMP to inhibit the GnRH response of the GnRHR promoter is associated with a loss of both JNK activation and GnRH-mediated recruitment of the primary AP-1-binding components.
The Sodium/Iodide Symporter (NIS): Characterization, Regulation, and Medical Significance
Authors: Dohán Orsolya , De la Vieja Antonio , Paroder Viktoriya , Riedel Claudia , Artani Mona , Reed Mia , Ginter Christopher S. , Carrasco Nancy
Published: February 2003

The Na+/I− symporter (NIS) is an integral plasma membrane glycoprotein that mediates active I− transport into the thyroid follicular cells, the first step in thyroid hormone biosynthesis. NIS-mediated thyroidal I− transport from the bloodstream to the colloid is a vectorial process made possible by the selective targeting of NIS to the basolateral membrane. NIS also mediates active I− transport in other tissues, including salivary glands, gastric mucosa, and lactating mammary gland, in which it translocates I− into the milk for thyroid hormone biosynthesis by the nursing newborn. NIS provides the basis for the effective diagnostic and therapeutic management of thyroid cancer and its metastases with radioiodide. NIS research has proceeded at an astounding pace after the 1996 isolation of the rat NIS cDNA, comprising the elucidation of NIS secondary structure and topology, biogenesis and posttranslational modifications, transcriptional and posttranscriptional regulation, electrophysiological analysis, isolation of the human NIS cDNA, and determination of the human NIS genomic organization. Clinically related topics include the analysis of congenital I− transport defect-causing NIS mutations and the role of NIS in thyroid cancer. NIS has been transduced into various kinds of cancer cells to render them susceptible to destruction with radioiodide. Most dramatically, the discovery of endogenous NIS expression in more than 80% of human breast cancer samples has raised the possibility that radioiodide may be a valuable novel tool in breast cancer diagnosis and treatment.
Ca2+ oscillations at fertilization in mammals are regulated by the formation of pronuclei
Authors: Marangos Petros , FitzHarris Greg , Carroll John
Published: February 2003

In mammals, the sperm triggers a series of cytosolic Ca2+oscillations that continue for ∼4 hours, stopping close to the time of pronucleus formation. Ca2+ transients are also seen in fertilized embryos during the first mitotic division. The mechanism that controls this pattern of sperm-induced Ca2+ signalling is not known. Previous studies suggest two possible mechanisms: first, regulation of Ca2+oscillations by M-phase kinases; and second, regulation by the presence or absence of an intact nucleus. We describe experiments in mouse oocytes that differentiate between these mechanisms. We find that Ca2+oscillations continue after Cdk1-cyclin B1 activity falls at the time of polar body extrusion and after MAP kinase has been inhibited with UO126. This suggests that M-phase kinases are not necessary for continued Ca2+oscillations. A role for pronucleus formation in regulating Ca2+signalling is demonstrated in experiments where pronucleus formation is inhibited by microinjection of a lectin, WGA, without affecting the normal inactivation of the M-phase kinases. In oocytes with no pronuclei but with low M-phase kinase activity, sperm-induced Ca2+ oscillations persist for nearly 10 hours. Furthermore, a dominant negative importin β that inhibits nuclear transport, also prevents pronucleus formation and causes Ca2+ oscillations that continue for nearly 12 hours. During mitosis, fluorescent tracers that mark nuclear envelope breakdown and the subsequent reformation of nuclei in the newly formed two-cell embryo establish that Ca2+ oscillations are generated only in the absence of a patent nuclear membrane. We conclude by suggesting a model where nuclear sequestration and release of a Ca2+-releasing activity contributes to the temporal organization of Ca2+ transients in meiosis and mitosis in mice.
TheC. elegans che-1gene encodes a zinc finger transcription factor required for specification of the ASE chemosensory neurons
Authors: Uchida Okiko , Nakano Hiroyuki , Koga Makoto , Ohshima Yasumi
Published: February 2003

Chemotaxis to water-soluble chemicals such as NaCl is an important behavior of C. elegans when seeking food. ASE chemosensory neurons have a major role in this behavior. We show that che-1, defined by chemotaxis defects, encodes a zinc-finger protein similar to the GLASS transcription factor required for photoreceptor cell differentiation inDrosophila, and that che-1 is essential for specification and function of ASE neurons. Expression of a che-1::gfp fusion construct was predominant in ASE. In che-1 mutants, expression of genes characterizing ASE such as seven-transmembrane receptors, guanylate cyclases and a cyclic-nucleotide gated channel is lost. Ectopic expression ofche-1 cDNA induced expression of ASE-specific marker genes, a dye-filling defect in neurons other than ASE and dauer formation.
Induction of neuron-specific glycosylation by Tollo/Toll-8, aDrosophilaToll-like receptor expressed in non-neural cells
Authors: Seppo Antti , Matani Parul , Sharrow Mary , Tiemeyer Michael
Published: February 2003

Specific glycan expression is an essential characteristic of developing tissues. Our molecular characterization of a mutation that abolishes neural-specific glycosylation in the Drosophila embryo demonstrates that cellular interactions influence glycan expression. The HRP epitope is an N-linked oligosaccharide expressed on a subset of neuronal glycoproteins. Embryos homozygous for the TM3 balancer chromosome lack neural HRP-epitope expression. Genetic and molecular mapping of the relevant locus reveals that Tollo/Toll-8, a member of the Toll-like receptor family, is altered on the TM3 chromosome. In wild-type embryos, Tollo/Toll-8 is expressed by ectodermal cells that surround differentiating neurons and precedes HRP-epitope appearance. Re-introduction of Tollo/Toll-8 into null embryos rescues neural-specific glycan expression. Thus, loss of an ectodermal cell surface protein alters glycosylation in juxtaposed differentiating neurons. The portfolio of expressed oligosaccharides in a cell reflects its identity and also influences its interactions with other cells and with pathogens. Therefore, the ability to induce specific glycan expression complements the previously identified developmental and innate immune functions of Toll-like receptors.
The zinc-finger protein CNBP is required for forebrain formation in the mouse
Authors: Chen Wei , Liang Yuqiong , Deng Wenjie , Shimizu Ken , Ashique Amir M. , Li En , Li Yi-Ping
Published: February 2003

Mouse mutants have allowed us to gain significant insight into axis development. However, much remains to be learned about the cellular and molecular basis of early forebrain patterning. We describe a lethal mutation mouse strain generated using promoter-trap mutagenesis. The mutants exhibit severe forebrain truncation in homozygous mouse embryos and various craniofacial defects in heterozygotes. We show that the defects are caused by disruption of the gene encoding cellular nucleic acid binding protein (CNBP);Cnbp transgenic mice were able to rescue fully the mutant phenotype.Cnbp is first expressed in the anterior visceral endoderm (AVE) and,subsequently, in the anterior definitive endoderm (ADE), anterior neuroectoderm (ANE), anterior mesendoderm (AME), headfolds and forebrain. InCnbp-/- embryos, the visceral endoderm remains in the distal tip of the conceptus and the ADE fails to form, whereas the node and notochord form normally. A substantial reduction in cell proliferation was observed in the anterior regions of Cnbp-/- embryos at gastrulation and neural-fold stages. In these regions, Myc expression was absent, indicating CNBP targets Myc in rostral head formation. Our findings demonstrate that Cnbp is essential for the forebrain induction and specification.