bluuebunny/crossref_metadata_2025 huggingface dataset:
A dendritic cell vaccine against invasive aspergillosis in allogeneic hematopoietic transplantation
Authors: Bozza Silvia , Perruccio Katia , Montagnoli Claudia , Gaziano Roberta , Bellocchio Silvia , Burchielli Emanuela , Nkwanyuo Gabriel , Pitzurra Lucia , Velardi Andrea , Romani Luigina
Published: June 2003

Dendritic cells (DCs) have a remarkable functional plasticity in response to conidia and hyphae of the fungus Aspergillus fumigatus. In the present study we sought to assess the capacity of DCs activated by live fungi or fungal RNA to generate antifungal immunity in vivo. We found that both human and murine DCs pulsed with live fungi or transfected with fungal RNA underwent functional maturation, as revealed by the up-regulated expression of histocompatibility class II antigen and costimulatory molecules and the production of interleukin 12 (IL-12) in response to conidia or conidial RNA and of IL-4/IL-10 in response to hyphae or hyphal RNA. DCs pulsed with conidia or transfected with conidial RNA activated antigen-specific, interferon γ (IFN-γ)-producing T lymphocytes in vitro and in vivo on adoptive transfer in mice otherwise susceptible to aspergillosis. TH1-dependent antifungal resistance could also be induced in mice receiving allogeneic bone marrow transplants and was associated with an accelerated recovery of myeloid and lymphoid cells. Because the efficacy of the infusion of DCs was superior to that obtained on the adoptive transfer of Aspergillus-specific T cells, these results indicate the vaccinating potential of DCs pulsed with Aspergillus conidia or conidial RNA in hematopoietic transplantation. (Blood. 2003;102:3807-3814)
A definitive role of Shp-2 tyrosine phosphatase in mediating embryonic stem cell differentiation and hematopoiesis
Authors: Chan Rebecca J. , Johnson Scott A. , Li Yanjun , Yoder Mervin C. , Feng Gen-Sheng
Published: June 2003

Homozygous mutant (Shp-2Δ46-110) embryonic stem (ES) cells exhibit decreased hematopoiesis; however, the point at which Shp-2 is critical for ES cell differentiation to hematopoietic cells is unknown. We characterized the differentiation defect of Shp-2Δ46-110 ES cells by examining early points of differentiation, conducting leukemia inhibitory factor (LIF)–stimulated biochemical analysis, and performing in vitro reconstitution studies with wild-type (WT) Shp-2. ES cell in vitro differentiation assays were used to compare the differentiation of WT, Shp-2Δ46-110, and reconstituted ES cells to mesoderm, by measuring brachyury expression, to hemangioblasts, by measuring blast colony-forming cell (BL-CFC) formation and flk-1 expression, and to hematopoietic progenitor colony-forming cells, by performing secondary plating assays. LIF-stimulated phospho-Stat3 (known to be critical for ES cell self-renewal and maintenance of an undifferentiated state) and phospho-Erk levels were examined by immunoblotting. ES cell survival, using annexin V staining, and secondary embryoid body (EB) formation were also evaluated. Differentiation to both mesoderm and hemangioblasts was lower in Shp-2Δ46-110 cells compared to WT cells. On reconstitution with WT Shp-2, expression of brachyury and flk-1 and differentiation to hemangioblasts and primitive and definitive hematopoietic progenitors were restored. LIF-stimulated phospho-Stat3 levels were higher, whereas phospho-Erk levels were lower in Shp-2Δ46-110 ES cells than in WT and reconstituted cells. The increased phospho-Stat3 levels correlated with increased Shp-2Δ46-110 ES cell secondary EB formation and survival. We conclude that normal Shp-2 function is critical for the initial step of ES cell differentiation to mesoderm and to hemangioblasts and acts within the LIF-gp130-Stat3 pathway to maintain a proper balance of ES cell differentiation, pluripotency, and apoptosis.
Gene profiling of a myeloma cell line reveals similarities and unique signatures among IL-6 response, N-ras-activating mutations, and coculture with bone marrow stromal cells
Authors: Croonquist Paula A. , Linden Michael A. , Zhao Fangyi , Van Ness Brian G.
Published: June 2003

ANBL-6, a myeloma cell line, proliferates in response to interleukin 6 (IL-6) stimulation, coculture with bone marrow stromal cells, and when harboring a constitutively active mutant N-ras gene. Eighteen samples, including 4 IL-6-treated, 3 mutant N-ras-transfected, 3 normal stroma-stimulated, 2 multiple myeloma (MM) stroma-stimulated, and 6 untreated controls were profiled using microarrays interrogating 12 626 genes. Global hierarchical clustering analysis distinguished at least 6 unique expression signatures. Notably, the different stimuli altered distinct functional gene programs. Class comparison analysis (P = .001) revealed 138 genes (54% involved in cell cycle) that distinguished IL-6-stimulated versus nontreated samples. Eighty-seven genes distinguished stroma-stimulated versus IL-6-treated samples (22% encoded for extracellular matrix [ECM] proteins). A total of 130 genes distinguished N-ras transfectants versus IL-6-treated samples (26% involved in metabolism). A total of 157 genes, 20% of these involved in signaling, distinguished N-ras from stroma-interacting samples. All 3 stimuli shared 347 genes, mostly of metabolic function. Genes that distinguished MM1 from MM4 clinical groups were induced at least by one treatment. Notably, only 3 genes (ETV5, DUSP6, and KIAA0735) are uniquely induced in mutant ras-containing cells. We have demonstrated gene expression patterns in myeloma cells that distinguish an intrinsic genetic transformation event and patterns derived from both soluble factors and cell contacts in the bone marrow microenvironment. (Blood. 2003;102:2581-2592)
Importance of baseline cotinine plasma values in smoking cessation: results from a double-blind study with nicotine patch
Authors: Paoletti P , Fornai E , Maggiorelli F , Puntoni R , Viegi G , Carrozzi L , Corlando A , Gustavsson G , Sawe U , Giuntini C
Published: June 2003

Nicotine replacement by transdermal patches is more effective than placebo in smoking cessation, but has a low success rate after one year (9-18%). We tested whether this was attributed to insufficient nicotine replacement. We conducted a randomized trial to investigate the effect on outcome of different doses of transdermal nicotine replacement after stratification according to baseline plasma cotinine values. Two hundred and ninety seven adult smokers were enrolled. Those with baseline cotinine < or = 250 ng.ml-1 (low cotinine) were randomly assigned to placebo (LC-P) or to 15 mg 16 h nicotine patches (LC-15), and those with baseline cotinine > 250 ng.mL-1 (high cotinine) were randomly assigned to 15 mg (HC-15) or 25 mg (HC-25) 16 h nicotine patches. Plasma nicotine and cotinine values, expired carbon monoxide and withdrawal symptoms were measured at scheduled intervals during treatment. Smokers in the LC-15 group had a significantly higher success rate than placebo (28 vs 9%). Smokers with high baseline cotinine had lower success rates, and a high dose of nicotine did not increase success rate (HC-25 9% vs HC-15 11%). Subjects in the HC-15 group had the lowest percentage of nicotine replacement and a higher prevalence of withdrawal symptoms than the HC-25 group. Replacement was similar in groups LC-15 and HC-25, but the success rate was significantly lower in HC-25 group, despite similar levels of withdrawal symptoms. We conclude that a higher success rate was obtained after one year in smokers with low baseline plasma cotinine values. Determination of plasma cotinine values may be, thus, helpful in identifying smokers who could benefit from transdermal nicotine replacement.
Increased content of hydrogen peroxide in the expired breath of cigarette smokers
Authors: Nowak D , Antczak A , Krol M , Pietras T , Shariati B , Bialasiewicz P , Jeczkowski K , Kula P
Published: June 2003

Cigarette smoking causes an influx of mononuclear phagocytes and polymorphonuclear leucocytes into the lower airways. These cells have altered oxygen metabolism and release more H2O2 than phagocytes from nonsmokers. In this study, we intended to determine whether asymptomatic cigarette smokers exhale more H2O2 than healthy nonsmokers. The content of H2O2 in the expired condensate of 27 nonsmokers and 33 cigarette smokers was measured spectrofluorimetrically (homovanillic acid method). The mean H2O2 level in the expired breath condensate of all cigarette smokers was about fivefold higher than that found in the whole nonsmoker group (0.24 +/- 0.32 versus 0.05 +/- 0.11 nM). However, only 16 smokers (49%) and 6 nonsmokers (22%) had detectable levels of H2O2 in expired breath that reached values 0.49 +/- 0.28 and 0.23 +/- 0.10 nM, respectively. Although the cigarette smoking status was similar for both male and female smokers, females expired 2.5 fold less H2O2 than males (0.15 +/- 0.24 (n = 21) versus 0.38 +/- 0.39 (n = 12) nM. No correlation was found between expired H2O2 levels and cigarette smoking status expressed as the daily cigarette consumption, cumulative cigarette consumption and urinary cotinine concentration. It is suggested that in some smokers, expressed H2O2 can be a noninvasive marker of oxidant overload in the lower airways related to cigarette smoking.
Relationships between radiological pattern and cell-mediated immune response in Mycoplasma pneumoniae pneumonia
Authors: Tanaka H , Koba H , Honma S , Sugaya F , Abe S
Published: June 2003

The aim of this study was to determine the relationship between the radiological pattern of Mycoplasma pneumoniae and the level of cell-mediated immunity of the host. Computed tomographic (CT) scans of the chest and the results of the purified protein derivative (PPD) test were studied during the acute stage of infection in 54 patients with M. pneumoniae pneumonia. The CT findings were used to divide the patients into two groups: one group had a predominance of nodular opacities with a centrilobular distribution (Group N; n = 29); and the other showed a predominance of an airspace consolidation (Group C; n = 25). Forty out of 54 subjects had negative tuberculin skin tests ( < 10 mm induration). The positive rate of PPD reaction was higher in Group N (13 out of 29) compared to Group C (1 out of 25) (p = 0.0005); whilst pleural effusion appeared more frequently in Group C (10 out of 25) than in Group N (3 out of 29) (p = 0.023). There was no significant difference between Groups N and C in white blood cell and lymphocyte counts, level of antibodies to M. pneumoniae in sera, and severity of the disease. These findings suggest that the characteristics of the host cell-mediated immunity might influence the pattern of pulmonary lesions in M. pneumoniae infection.
Integrin alpha E beta 7 expression on BAL CD4+, CD8+, and gamma delta T-cells in bleomycin-induced lung fibrosis in mouse
Authors: Braun RK , Sterner-Kock A , Kilshaw PJ , Ferrick DA , Giri SN
Published: June 2003

CD4, CD8, and gamma delta T-cells located in the epithelium express the integrin alpha E beta 7 that binds to E-cadherin on the epithelium. Gamma delta T-cells mediate specific cellular immune functions and can recognize damaged cells directly. It was, therefore, of interest to analyse the presence of gamma delta T-cells and the expression of alpha E beta 7 on gamma delta T-cells in the bleomycin (BLM) model of pulmonary fibrosis. Lung fibrosis was induced by a single intratracheal instillation of BLM (0.125 U.mouse-1), and bronchoalveolar lavage (BAL) T-cell subpopulations were examined at various time-points for the expression of the integrin alpha E beta 7 by flow cytometry. CD4+ T-cells accounted for about 40% of the lymphocytes, compared to about 10% of CD8+ T-cells and 10-14% gamma delta T-cells. Within the CD4+ T-cell population the proportion of alpha E beta 7+ cells decreased between Days 2 and 22 from 36 to 11%. The percentage of alpha E beta 7+ CD8+ T-cells increased at the same time from 4 to 68%. However, more than 80% of the gamma delta T-cells in BAL fluid expressed alpha E beta 7 at all time-points. The surface-expression of this integrin on gamma delta T-cells was 2-3 times higher than on CD4+ or CD8+ T-cells. This predominant expression of alpha E beta 7 on gamma delta T-cells suggests a role for these cells in the pathogenesis of bleomycin-induced lung fibrosis.
Relevance of asbestos bodies in sputum
Authors: Teschler H , Thompson AB , Dollenkamp R , Konietzko N , Costabel U
Published: June 2003

The presence of asbestos bodies (ABs) in sputum specimens of individuals with occupational asbestos exposure has been well-documented. The aim of this study was to determine their clinical relevance in comparison to the concentration of AB in bronchoalveolar lavage (BAL) and lung tissue. Subjects were included following a well-documented exposure of asbestos history (n = 93) or BAL fluid analysis positive for ABs (n = 42). The subjects with a well documented history of AB exposure were divided into three groups: heavy (Group 1, n = 29); moderate (Group 2, n = 31); or occasional exposure (Group 3, n = 33). BAL fluid was available from all subjects, and lung tissue from 21 subjects. To assess the variability, 10 sputum positive subjects collected subsequent sputum on days 2, 7, 14, 30 and 90. ABs were determined by light microscopy after membrane filtration of specimen digests. The mean sputum AB content was highest in Group 1 (2.4 +/- 5.5 AB.mL-1), lower in Group 2 (0.2 +/- 0.3 AB.mL-1) and lowest in Group 3 (0.1 +/- 0.1 AB.mL-1) suggesting a correlation with cumulative exposure. However, many negative sputum samples were noted, when BAL specimens were positive. The AB content of sputum and BAL specimens did not correlate. ABs were found in sputum of all subjects with a tissue content of > 1,000 AB-cm-3, but in none with contents of < 1,000 AB-cm-3. Substantial variability of ABs was found in the five sequentially collected sputa of 10 initially positive patients (coefficient of variation 28-93%), but only two false negatives were found in these 50 samples. Thus, sputum analysis for asbestos bodies is an insensitive method for assessing the lung asbestos burden, much less sensitive than bronchoalveolar lavage fluid analysis. However, a sputum sample positive for asbestos bodies is suggestive of a high lung asbestos burden.
Inhalation of hypertonic saline aerosol enhances mucociliary clearance in asthmatic and healthy subjects
Authors: Daviskas E , Anderson SD , Gonda I , Eberl S , Meikle S , Seale JP , Bautovich G
Published: June 2003

Hyperosmolarity of the airway surface liquid (ASL) has been proposed as the stimulus for hyperpnoea-induced asthma. We found previously that mucociliary clearance (MCC) was increased after isocapnic hyperventilation (ISH) with dry air, and we proposed that the increase related to transient hyperosmolarity of the ASL. We investigated the effect of increasing the osmolarity of the ASL on MCC, by administering an aerosol of concentrated salt solution. MCC was measured using 99mTc-sulphur colloid, gamma camera and computer analysis in 12 asthmatic and 10 healthy subjects on three separate days, involving administration of each of the following: 1) ultrasonically nebulized 14.4% saline; 2) ultrasonically nebulized 0.9% saline; and 3) no aerosol intervention (control). The (mean +/- SD) volume of nebulized 14.4% saline was 2.2 +/- 1.2 mL for asthmatics and 3.2 +/- 0.7 mL for healthy subjects. This volume was delivered over a period of 5.4 +/- 1.3 and 6.4 +/- 0.7 min for asthmatic and healthy subjects, respectively. The airway response to 14.4% saline was assessed on a separate visit and the fall in forced expiratory volume in one second (FEV1) was 22 +/- 4% in the asthmatic and 3 +/- 2% in the healthy subjects. Compared to the MCC with the 0.9% saline and control, the hypertonic aerosol increased MCC in both groups. In asthmatic subjects, MCC of the whole right lung in 1 h was 68 +/- 10% with 14.4% saline vs 44 +/- 14% with 0.9% saline and 39 +/- 13% with control. In healthy subjects, MCC of the whole right lung in 1 h was 53 +/- 12% with 14.4% saline vs 41 +/- 15% with 0.9% saline and 36 +/- 13% with control. We conclude that an increase in osmolarity of the airway surface liquid increases mucociliary clearance both in asthmatic and healthy subjects. These findings are in keeping with our previous suggestion that the increase in mucociliary clearance after isotonic hyperventilation with dry air is due to a transient hyperosmolarity of the airway surface liquid.
Adenosine deaminase (ADA) isoenzyme analysis in pleural effusions: diagnostic role, and relevance to the origin of increased ADA in tuberculous pleurisy
Authors: Valdes L , San Jose E , Alvarez D , Valle JM
Published: June 2003

The rise in adenosine deaminase (ADA) activity in the pleural fluid of tuberculous pleurisy patients, though used for diagnosis, is of unknown origin. In this work, we determined ADA activity and the activities of 2'-deoxyadenosine deaminase and ADA-2 in 350 patients. We also considered whether the results throw light on the origin of high pleural fluid ADA in tuberculous pleurisy and estimated the diagnostic efficiency of 2'-deoxyadenosine deaminase, ADA-2 and total ADA activities with and without the inclusion of the 2'-deoxyadenosine deaminase/ADA activity ratio in a combined criterion. The 350 pleural effusions were classified by previously established criteria as transudates (60 males/18 females) or as tuberculous (49 males/27 females), neoplastic (50 males/39 females), parapneumonic (36 males/19 females), empyematous (11 males/3 females), or miscellaneous (25 males/13 females) exudates. Total ADA, ADA-2 and 2'-deoxyadenosine deaminase activities were, respectively, 127.5 +/- 2.9, 103 +/- 29.5 and 42.8 +/- 14 U.L-1 in tuberculous exudates. With diagnostic thresholds of 47, 40 and 22 U.L-1 respectively, the sensitivities of ADA, ADA-2 and 2'-deoxyadenosine deaminase for tuberculosis were 100, 100 and 95%; their specificities 91, 96 and 92%; and their efficiencies 93, 97 and 93%, respectively. One hundred and one effusions (all 76 tuberculous, 12 neoplastic, 4 parapneumonic and 9 empyematous exudates) had total ADA levels > 47 U.L-1; of these, 8 neoplastic, 1 parapneumonic and all the tuberculous exudates had a 2'-deoxyadenosine deaminase/ADA activity ratio < 0.49. The criterion of simultaneously having ADA > 47 U.L-1, ADA-2 > 40 U.L-1 and a 2'-deoxyadenosine deaminase/ADA activity ratio < 0.49 was satisfied by all the tuberculous effusions but only eight others (all neoplastic) (sensitivity 100%, specificity 97%, efficiency 98%). We conclude that: 1) high total ADA activity in tuberculous pleural effusions is due mainly to an increase in ADA-2, and, therefore, originated from the only known source monocytes and macrophages; 2) ADA-2 was a more efficient diagnostic marker of tuberculous pleurisy than total ADA activity, although the difference was not statistically significant; and 3) among effusions with high total ADA the 2'-deoxyadenosine deaminase/ADA activity ratio differentiates tuberculous effusions from empyemas and parapneumonic effusions, but fails to discriminate well between tuberculous and neoplastic effusions.
In vitro modulation of induced neutrophil activation by different surfactant preparations
Authors: Tegtmeyer FK , Gortner L , Ludwig A , Brandt E
Published: June 2003

Endotracheal surfactant administration has gained an important role in the treatment of respiratory failure. Polymorphonuclear neutrophil granulocyte (PMN) activation mediated by chemoattractants, such as interleukin-8 (IL-8), neutrophil-activating peptide-2 (NAP-2) and formylated bacterial oligopeptides, has been found to be involved in the pathophysiology of acute respiratory failure. We investigated potential modulating effects of commercial surfactant preparations (Exosurf, Alveofact, Curosurf and Survanta) on spontaneous and chemoattractant-induced PMN function. Isolated cytochalasin B (CytB)-treated PMNs from healthy adults were incubated with increasing concentrations of surfactant. The response of the cells was measured in terms of elastase release from the lysosomes within 30 min. The PMNs showed no direct activation by any of the surfactants tested. However, when cells were stimulated with suboptimal dosages of chemokines, such as IL-8 (2 nM) or NAP-2 (100 nM), or formyl-methionyl-leucyl-phenylalanine (fMLP) (50 nM), and co-incubated with increasing concentrations of surfactant (0.05-8 mg.mL-1) the release of elastase was markedly modulated depending on the surfactant preparation used. Whilst Exosurf and Alveofact showed only modest effects on the elastase release induced by all three mediators, Curosurf and Survanta markedly inhibited the cellular response in a dose-dependent manner. At concentrations above 1 mg.mL-1, Curosurf and Survanta decreased the IL-8-, NAP-2- and fMLP-induced elastase release by 83, 67 and 90%, and by 82, 75 and 80%, respectively. In conclusion, exogenous surfactant may modulate the inflammatory response of the airways by affecting the chemoattractant-induced polymorphonuclear neutrophil activation. Surfactant preparations with inhibiting properties on neutrophil activation may participate in the prevention of neutrophil-induced lung damage.
Tracheal distensibility in cystic fibrosis
Authors: Lebecque P , Liistro G , Veriter C , Stanescu D
Published: June 2003

Size and distensibility of large airways have important implications for flow limitation and the efficacy of coughing. From radiological and functional data, some authors have suggested an increased size and distensibility of the trachea in cystic fibrosis (CF). Using computed tomography (CT) we compared size and distensibility of the trachea in 5 cystic fibrosis patients and five age- and height-matched healthy volunteers. Tracheal cross-sectional area was measured 25 mm below the cricoid cartilage. CT recordings were made at functional residual capacity, at 0 and +20 cmH2O mouth pressure. Inductive plethysmography was used to check that during these manoeuvres lung volume did not change and that the glottis remained open. Tracheal cross-sectional area and derived indices of tracheal distensibility were similar in the two groups. This study does not support the concept of an increased size and distensibility of the trachea in cystic fibrosis.
Palatopharyngeus has respiratory activity and responds to negative pressure in sleep apnoeics
Authors: Mortimore IL , Douglas NJ
Published: June 2003

The intrinsic tongue muscle, genioglossus, and soft palatal muscles, tensor palatini, levator palatini and palatoglossus, are known to exhibit phasic respiratory activity and to respond reflexly to negative pressure in man, which may be important in the maintenance of upper airway patency. We hypothesized that the palatopharyngeus muscle should also have respiratory activity and increased activity in response to negative upper airway pressure. We have, therefore, examined the palatopharyngeus and the antagonist muscle, levator palatini, in eight awake sleep apnoea patients, using bipolar electromyography during nose- or mouth-breathing in different postures, and with or without application of negative pressure. Overall, palatopharyngeus and levator palatini demonstrated phasic respiratory activity. Palatopharyngeus demonstrated increased activity in the supine compared to erect posture. Analysis by route of respiration showed palatopharyngeus to be more active in the supine posture when nose-breathing compared to mouth-breathing. Graded negative pressure application caused significant increases in palatopharyngeus and levator palatini activity when applied via the mouth. Nasal negative pressure application caused a nonsignificant trend to increasing palatopharyngeus activity with increasing negative pressure compared to a significant increase for levator palatini. We conclude that palatopharyngeus and levator palatini demonstrate respiratory activity and reflex activation in response to negative pressure. Palatopharyngeus may, therefore, have a role as an upper airway dilator. The differential response of palatopharyngeus to oral and nasal negative pressure application may be important in the pathogenesis of sleep apnoea.
Peak expiratory flow and the resistance of the mini-wright peak flow meter
Authors: Pedersen OF , Rasmussen TR , Omland O , Sigsgaard T , Quanjer PH , Miller MR
Published: June 2003

The purpose of this study was to examine whether the resistance of the peak flow meter influences its recordings. One hundred and twelve subjects, (healthy nonsmokers and smokers and subjects with lung diseases) performed three or more peak expiratory flow (PEF) manoeuvres through a Fleisch pneumotachograph with and without a mini-Wright peak flow meter added in random order as a resistance in series. The results were as follows. In comparison with a pneumotachograph alone, peak flow measured with an added mini-Wright meter had a smaller within-test variation, defined as the difference between the highest and second highest values of PEF in a series of blows. The mean (SE) variation was 14 (1.3) L.min-1 and 19 (1.5) L.min-1 with and without meter added, respectively. In comparison with the pneumotachograph alone, the addition of the mini-Wright meter caused PEF to be underread, especially at high flows. The difference (PEF with meter minus PEF without meter) = -0.064 (average PEF) -8 L.min-1; R2 = 0.13. The mean difference was -7.8 (1.1) %, and increased numerically for a given PEF, when maximal expiratory flow when 75% forced vital capacity remains to be exhaled (MEF75%FVC) decreased. The reproducibility criteria for repeated measurements of peak flow are more appropriately set at 30 L.min-1 than the commonly used 20 L.min-1, because a within-test variation of less than 30 L.min-1 was achieved in 76% of the subjects without PEF meter inserted and in 88% with meter inserted, with no difference between healthy untrained subjects and patients. The resistance of the peak expiratory flow meter causes less variation in recordings but reduces peak expiratory flow, especially at high values and when the peak is large as compared with the rest of the maximal expiratory flow-volume curve.
Mesenchymal chondrosarcoma of the pleura
Authors: Luppi G , Cesinaro AM , Zoboli A , Morandi U , Piccinini L
Published: June 2003

A 52 year old man developed an extraskeletal mesenchymal chondrosarcoma (ESMC) arising from the pleura. Clinically, the tumour mimicked a mesothelioma. Fine needle biopsy was consistent with the diagnosis of sarcomatoid mesothelioma. Histological examination of multiple tumour samples, supported by immunohistochemical characterization, made it possible to correctly diagnose extraskeletal mesenchymal chondrosarcoma.
Size parameters, size-class distribution and area-number relationship of microscopic charcoal: relevance for fire reconstruction
Authors: Tinner Willy , Hu Feng Sheng
Published: June 2003

Charcoal analysis was conducted on sediment cores from three lakes to assess the relationship between the area and number of charcoal particles. Three charcoal-size parameters (maximum breadth, maximum length and area) were measured on sediment samples representing various vegetation types, including shrub tundra, boreal forest and temperate forest. These parameters and charcoal size-class distributions do not differ statistically between two sites where the same preparation technique (glycerine pollen slides) was used, but they differ for the same core when different techniques were applied. Results suggest that differences in charcoal size and size-class distribution are mainly caused by different preparation techniques and are not related to vegetation-type variation. At all three sites, the area and number concentrations of charcoal particles are highly correlated in standard pollen slides; 82–83% of the variability of the charcoal-area concentration can be explained by the particle-number concentration. Comparisons between predicted and measured area concentrations show that regression equations linking charcoal number and area concentrations can be used across sites as long as the same pollen-preparation technique is used. Thus it is concluded that it is unnecessary to measure charcoal areas in standard pollen slides – a time-consuming and tedious process.
Human impact on the Irish landscape during the late Holocene inferred from palynological studies at three peatland sites
Authors: Cole Edwina E. , Mitchell Fraser J.G.
Published: June 2003

Pollen data covering the last 1200 years from a transect of three peatland sites across Ireland are reported. The data reveal reductions in woodland and increased anthropogenic activity over time. A decline in Corylus-type pollen at around AD 1750 was a dramatic and concurrent event at all three sites which coincided with more intensive land use. Multivariate data analysis reveals that prior to the Corylus-type decline distinct regional differences occurred between the sites, but that after it this regional variation was lost. It is concluded that more intense land use led to greater regional uniformity. Rising human population coincides with evidence for intense land use in the pollen data. The failure of the potato crop and the Great Famine of 1845 led to a population crash, but this had limited impact on the landscape. The imprint of human activity on the landscape over the last 1200 years appears to have overwhelmed any impacts that could be attributed solely to climatic change associated with the ‘Mediaeval Warm Period’, the ‘Little Ice Age’ or late twentieth-century warming.
Stratigraphy of late-Holocene deposits of the ancient harbour of Marseilles, southern France
Authors: Morhange C. , Blanc F. , Schmitt-Mercury S. , Bourcier M. , Carbonel P. , Oberlin C. , Prone A. , Vivent D. , Hesnard A.
Published: June 2003

The late-Holocene stratigraphy of Marseilles harbour is presented together with archaeological evidence and radiocarbon data. An anthropogenic oyster midden, dated between c. 4260 and 3400 14C yr BP is followed by a period of siltation that ended the accretionary growth of an algal (marl) deposit. This event was caused by early human settlement. Subsequently the coastline was subject to progradation. It is argued here that the development of the first town of Marseilles, c. 2600 years ago, accelerated soil erosion and sediment deposition in the harbour area.
Isotopic variation in modern lake waters from western Greenland
Authors: Leng Melanie J. , Anderson N. John
Published: June 2003

The stable-isotope composition of lake waters along Sïndre Strïmfjord in western Greenland have been measured both spatially (coast to ice sheet) and temporally (up to five times between 1998–2000) and the data compared to local climatic information. There is a climatic gradient along Sïndre Strïmfjord, with the head of the fjord characterised by a low Arctic continental climate, while the coast has a more maritime climate (increased precipitation and reduced annual temperature range). The change in climate from continental to maritime is reflected in the isotopic composition of the lakes. The inland lakes have δ18O and dD values which lie on evaporation trends away from meteoric water composition. The coastal lakes have δ18O and dD compositions close to meteoric water. Short-term seasonal trends are superimposed on longer term variation. For example, the relatively dry years (precipitation lower than the long-term annual mean) of 1998 and 1999 are seen in the smaller lakes as isotopic enrichment, but the larger lakes are buffered in their response to short-term changes. The small coastal lakes tend to have depleted δ13C derived predominantly from organic material, while the inland lakes have contributions from both organic carbon and from exchange with isotopically heavier atmospheric CO2. This study demonstrates the importance of characterizing local hydrological settings in the interpretation of lacustrine isotope records. In the Arctic, this type of information is especially useful for identifying lakes that have the potential to record arid intervals since precipitation/evaporation adjustments, especially toward greater aridity, may not be recorded in the Greenland ice-core records.
A synthesis of abrupt changes in the Asian summer monsoon since the last deglaciation
Authors: Morrill Carrie , Overpeck Jonathan T. , Cole Julia E.
Published: June 2003

We have compiled 36 previously published palaeoclimate records to determine the timing and spatial pattern of century-scale abrupt changes in Asian monsoon precipitation since the last deglaciation. We identify abrupt events from (1) the interpretations of the authors of these records and (2) the more objective moving t-test calculation. Our results indicate that abrupt climatic changes occurred at ~11.5 cal. ka, 4.5–5.0 cal. ka and ad 1300. At the start of the Holocene (~11.5 cal. ka), Asian monsoon precipitation increased dramatically. This climatic change is synchronous with an abrupt warming in the North Atlantic. During the middle Holocene, there was a time of preferred and widespread weakening in monsoon strength (~4.5–5.0 cal. ka). This result contradicts previous notions of either a gradual trend towards drier conditions or a series of abrupt events that occurred in an unorganized fashion across space and time. The middle-Holocene abrupt event could have been synchronous with an abrupt cooling event in the North Atlantic, as well as a warming and intensification of internannual variability in the tropical Pacific. In contrast to previous periods, precipitation changes at ad 1300 have a heterogeneous spatial pattern. We find no conclusive evidence for a change in the Asian monsoon at ~8.2 cal. ka, as suggested by several previous studies. More high-resolution data may be needed to observe this short-lived event. Overall, our results attest to the potential for rapid and major shifts in Asian monsoon precipitation that may be triggered by variations in other components of the climatic system.
A chironomid-based Holocene summer air temperature reconstruction from the Swiss Alps
Authors: Heiri Oliver , Lotter André F. , Hausmann Sonja , Kienast Felix
Published: June 2003

We developed a quantitative chironomid-July air temperature inference model based on surface sediments from 81 Swiss lakes and applied it to the Holocene subfossil chironomid record of Hinterburgsee, a small subalpine lake in the northern Swiss Alps (present-day mean July air temperature of 11.3°C). After smoothing to reduce the high between-sample variability of inferred temperatures, the reconstruction indicates July air temperatures of 10.4– 10.9°C at the end of the Younger Dryas, of 11.9–12.8°C during the early and mid-Holocene (11500–4000 cal. BP), and slightly lower temperatures of 11.5–12.0°C during the late Holocene (3500–1000 cal. BP). A warming trend inferred for the past millennium is most likely an artifact of human impact on Hinterburgsee's chironomid fauna, rather than a genuine temperature signal. The most prominent climatological events during the Holocene were two periods of lower temperatures at c. 10700–10500 cal. BP and 8200–7700 cal. BP and an abrupt shift to a cooler late-Holocene climate around 4000–3700 cal. BP. Although the chironomid-inferred climate signals were within the prediction error of the model (1.51°C), major inferred temperature changes agree well with other northern and central European climate reconstructions and underline the potential of subfossil chironomid analysis to reconstruct even the moderate climatic changes within the Holocene.
Holocene lake succession and palaeo-optics of a Subarctic lake, northern Québec, Canada
Authors: Saulnier-Talbot Émilie , Pienitz Reinhard , Vincent Warwick F.
Published: June 2003

Two diatom-based transfer functions for the reconstruction of past levels of dissolved organic carbon (DOC) and water colour were applied to fossil diatom species assemblages from a coastal isolation basin on the eastern shore of Hudson Bay. Diatom stratigraphic changes and the diatom-inferred patterns of limnological change following the retreat of Holocene marine waters of the Tyrrell Sea revealed a highly variable Holocene lake trajectory associated with successional shifts in lake catchment vegetation and soil development. The main trends observed in the Holocene history of Lake Kachishayoot are: (1) a progressive loss of alkalinity over time; and (2) abrupt increases in DOC and water colour that coincide with the arrival of spruce (Picea mariana) in the catchment. Reconstructed DOC allowed the estimation of past depths of ultraviolet (UV) penetration in the water-column of Lake Kachishayoot. Past variations in biological UV exposure were inferred using optical models based on DOC concentrations and the response curves for DNA damage and UV photoinhibition of photosynthesis. The palaeoecological analyses revealed large changes in the underwater photobiological environment over the course of the Holocene period, from extremely high UV exposure after the initial formation of the lake and its isolation from the sea, to an order-of-magnitude lower biological UV exposure under the present conditions of catchment vegetation.
Temporal changes of ostracode assemblages and anthropogenic pollution during the last 100 years, in sediment cores from Hiroshima Bay, Japan
Authors: Yasuhara Moriaki , Yamazaki Hideo , Irizuki Toshiaki , Yoshikawa Shusaku
Published: June 2003

Temporal changes of ostracodes during the last 100 years observed in three sediment cores from Hiroshima Bay, the Seto Inland Sea, Japan, provide valuable information about influences on ostracodes caused by anthropogenic pollution. This is the first detailed report of historical records of the relationship between ostracodes and pollution established from core samples drilled in the polluted inner bay. At least 38 ostracode species were identified from 40 samples. Based on biofacies, the density of ostracodes and the faunal structure, it is elucidated that industrialization combined with the effects of the second world war caused a decrease in the density and a increase in the equitability of ostracodes, and that anthropogenic pollution caused a simplification of ostracode assemblages in Hiroshima Bay. The response of two particular ostracode species to anthropogenic pollution is also demonstrated. Callistocythere alata was sensitive and Bicornucythere bisanensis has a strong resistance for anthorogenic pollution in ostracode species. Thus, the relative frequencies of these two ostracodes can be used as an indication of such pollution. We discuss the limitations of using recent ostracode assemblages in the analysis of the palaeoenvironment, resulting from the changes induced by anthropogenic pollution during the last 100 years.
Forest clearance and regrowth in northern Ethiopia during the last 3000 years
Authors: Darbyshire Iain , Lamb Henry , Umer Mohammed
Published: June 2003

Pollen and charcoal analysis of sediment cores from two lakes in the highlands of northern Ethiopia provide evidence that the vegetation has changed in response to human impact during the last 3000 years. The natural, pre-disturbance vegetation of the area was Podocarpus-Juniperus forest. At about 500 bc, following Semitic immigration to northern Ethiopia, the forests were cleared and replaced by a secondary vegetation of Dodonaea scrub and grassland that persisted for 1800 years. Grasslands were dominant from about ad 1200 to 1400, probably as a result of further intensification of grazing, perhaps exacerbated by drought. Juniperus forest, with Olea and Celtis, then expanded from ad 1400 to 1700, possibly because of drought-induceddepopu lation followed by increased rainfall. Deforestation and soil erosion has again intensified during the last three centuries. Since forest regrowth was possible after 1800 years of human impact, northern Ethiopia should again be capable of supporting forest under appropriate land management.
Plant cultivation and forest clearance by prehistoric North Americans: pollen evidence from Fort Ancient, Ohio, USA
Authors: McLauchlan Kendra
Published: June 2003

Archaeological records show that, as early as 2000–1500 bc, Native Americans in the eastern USA domesticated a group of native plant species with starchy or oily seeds that helped support extensive Woodland societies. Previously, the location and extent of cultivation of these ancient crop plants has been unknown, but was hypothesized to be small clearances on river floodplains. Here, pollen analyses of two 2000-year-old sediment records from Fort Ancient, an upland Hopewell archaeological site in southwestern Ohio, show exceptionally high amounts of pollen from cultigens- Iva annua, Polygonum erectum and Chenopodium – deposited during Hopewell occupation of the site (100 bc to ad 400). It is likely that this earthwork is a site of prehistoric cultivation, not exclusively a ceremonial structure. Pollen spectra indicate the area surrounding the ponds was largely deforested, and the sediment record indicates high rates of erosion during this time. Therefore, North American Woodland societies were likely modifying vegetation more extensively through agriculture and other land-clearing activities than has been assumed previously.
European impact on fire regimes and vegetation dynamics at the steppe-forest ecotone of southern Patagonia
Authors: Huber Ulli M. , Markgraf Vera
Published: June 2003

A macroscopic charcoal, pollen and peat macrofossil record from Rio Rubens Bog in southern Patagonia, covering the last c. 1200 years, provides detailed evidence concerning European impact on veg etation and fire frequency. Based on 210Pb and 14C chronologies, we demonstrate that thefirst introduction of the weed Rumex acetosella occurred during early European contact in the sixteenth century or shortly thereafter. Thus, the first occurrence of this pollen type should not be used as a time marker for permanent European settlement in the late nineteenth to early twentieth centuries. Local fires did not occur for more than 900 cal. yr prior to European contact, and became frequent, with fire-return intervals on the order of 100 cal. yr, after c. ad 1600. Without an independent chronology, the onset of high fire activity would have been erroneously attributed to the initiation of European settlement in the late nineteenth century, based on the presence of Rumex acetosella. The coincidence between weed introduction and fires, in combination with wet climate, favours a change in human ignition frequency as the driving factor for frequent fires after c. ad 1600. We speculate that Europeans may have impacted fire frequency by indirectly influencing aboriginal hunting through the introduction of horses. Whereas changes in forest vegetation during early European contact were small, subsequent European settlement initiated a period of severe forest destruction through burning, logging and grazing. The most rapid and severe phase of deforestation has been associated with large-scale, export-orientated logging since the 1980s.
Holocene palaeoclimates of southern Patagonia: limnological and environmental history of Lago Cardiel, Argentina
Authors: Markgraf Vera , Bradbury J. Platt , Schwalb Antje , Burns Stephen J. , Stern Charles , Ariztegui Daniel , Gilli Adrian , Anselmetti Flavio S. , Stine Scott , Maidana Nora
Published: June 2003

Multiproxy palaeoenvironmental and palaeolimnological analyses of two Holocene-age sediment cores from the margin of Lago Cardiel, a 76 m deep, closed-basin lake in southern Patagonia (latitude 49°S), provide information on lake-level changes that can be related to regional palaeoclimate scenarios. Sedimentol ogic (magnetic susceptibility, organic and inorganic carbon content) and environmental indicators (pollen, dia toms, ostracodes and stable isotopes on ostracodes) show lake levels markedly higher than today during the early Holocene, following a rapid lake-level rise after a desiccation phase prior to 11000 BP. After about 6000 BP, lake levels were generally lower, but underwent repeated fluctuations. These inferred changes support the previously proposed view that the southern westerly stormtracks were focused (zonal) north of latitude 50°S during the early Holocene, allowing for Antarctic cold fronts to bring easterly moisture to southern Patagonia, whereas during the late Holocene the stormtracks shifted seasonally, with an overall more meridional behaviour, resulting in less and more variable moisture at these latitudes.
Expression of Bambi Is Widespread in Juvenile and Adult Rat Tissues and Is Regulated in Male Germ Cells
Authors: Loveland Kate Lakoski , Bakker Marilyn , Meehan Terri , Christy Elizabeth , von Schönfeldt Viktoria , Drummond Ann , de Kretser David
Published: June 2003

Members of the TGFβ superfamily may compete for receptor occupancy and intracellular signaling molecules in specific developmental circumstances. We explored the potential importance of the TGFβ family inhibitor, Bambi (Bmp and activin membrane-bound inhibitor) by examining its pattern of mRNA expression in juvenile and adult rat tissues, with a focus on reproductive organs. The 1.8-kb transcript was ubiquitous, whereas a 3-kb transcript was unique to enriched spermatocyte and spermatid cell fractions and adult testis. The full-length rat cDNA is 89% (nucleic acid) and 95% (amino acid) identical to its human homolog, hnma. Using in situ hybridization, Bambi mRNA was detected in granulosa and thecal cells of adult ovaries and in spermatogonia, spermatocytes, round spermatids, and Sertoli cells of adult testes. In addition to a persistent signal in Sertoli cells in juvenile testes, this mRNA within germ cells appeared dramatically increased as gonocytes matured into spermatogonia immediately after birth. These data indicate that TGFβ superfamily signaling within male germ cells is down-regulated at the onset of spermatogenesis. The addition of exogenous activin A to 24-h cultures of newborn rat testis fragments decreased the Bambi mRNA level. Regulated Bambi mRNA synthesis may contribute to TGFβ superfamily signaling modulation in several organs, as suggested by its discrete expression switch in male germ cells.
Acute in Vivo Elevation of Insulin-Like Growth Factor (IGF) Binding Protein-1 Decreases Plasma Free IGF-I and Muscle Protein Synthesis
Authors: Lang Charles H. , Vary Thomas C. , Frost Robert A.
Published: June 2003

This study examined whether the acute elevation of IGF-binding protein-1 (IGFBP-1) decreases the plasma free IGF-I concentration and alters in vivo rates of muscle protein synthesis and glucose uptake. The plasma concentration of human IGFBP-1 was increased to approximately 95 ng/ml in conscious catheterized rats infused iv with human IGFBP-1 for 4 h. Infusion of IGFBP-1 also increased the concentration of endogenous (e.g. rat) IGFBP-1 in the blood, and this response was associated with a 2- to 3-fold elevation of IGFBP-1 mRNA in liver and kidney. IGFBP-1 did not significantly alter the plasma concentration of total IGF-I, but decreased circulating free IGF-I levels by about 50%. IGFBP-1 decreased protein synthesis in the predominantly fast-twitch gastrocnemius muscle (20%), and this change resulted from a decreased translational efficiency that was associated with a decreased phosphorylation of S6K1, but not 4E-BP1. Complementary studies demonstrated that IGFBP-1 also decreased the rates of protein synthesis under basal conditions and in response to stimulation by IGF-I when added in vitro to the fast-twitch epitrochlearis muscle. In contrast, IGFBP-1 did not alter in vivo-determined rates of protein synthesis in the slow-twitch soleus muscle, heart, liver, or kidney. The infusion of IGFBP-1 did not significantly alter the plasma glucose or lactate concentration or the whole body rate of glucose production or disposal. The above-mentioned changes were not mediated indirectly by changes in the plasma insulin or corticosterone concentrations, decreased high energy phosphate content in muscle, or hepatoxicity produced by the infused IGFBP-1. These results demonstrate that acute in vivo elevation in IGFBP-1, of the magnitude observed in various catabolic conditions, is capable of selectively decreasing protein synthesis in fast-twitch skeletal muscle and up-regulating the hepatic and renal syntheses of IGFBP-1 per se. Hence, elevations in circulating and tissue levels of IGFBP-1 may be an important mediator for the muscle catabolism observed in various stress conditions.