bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pancreas transcription factor 1α expression is regulated in pancreatitis
Authors: Molero X. , Adell T. , Skoudy A. , Padilla M. A. , Gómez J. A. , Chalaux E. , Malagelada J. R. , Real F. X. 
Published: September 2007

AbstractBackground  Expression of acinar cell‐specific genes requires the pancreas transcription factor 1α (Ptf1α). p48 is the only component of Ptf1α that is involved in both acinar gene regulation and pancreatic ontogenesis.Materials and methods  To determine whether Ptf1α/p48 expression is regulated during pancreatitis, acute pancreatitis was induced in rats by repeated caerulein injections; early chronic pancreatitis by the combined administration of caerulein and cyclosporin A; and focal pancreas fibrosis by trinitrobenzene sulfonic acid infusion into the pancreatic duct. AR42J cells were used to examine caerulein effects on acinar cells. Ptf1α/p48 expression was examined using immunohistochemistry, Western blotting, and qRT‐PCR methods.Results  In acute pancreatitis, Ptf1α/p48 decreased markedly within 6 h as determined by Western blotting and immunohistochemistry. After 24 h, Ptf1α/p48 increased continuously and normalized at day six. In contrast, pancreas amylase reached a nadir at 48 h, when Ptf1α/p48 had largely recovered. In the early chronic pancreatitis model Ptf1α/p48 levels did not completely recover even at day 14, and this was associated with a failure to restore normal histology and amylase content. qRT‐PCR showed that p48 mRNA were reduced after pancreatitis induction and were followed by a decrease in elastase mRNA. In the focal pancreas fibrosis model, Ptf1α/p48 expression was undetectable in areas with substantial acinar cell loss and tubular complexes. Caerulein did not affect Ptf1α/p48 expression in AR42J cells.Conclusions  Ptf1α/p48 protein and mRNA levels are regulated in acute and chronic experimental pancreatitis. Inability to re‐express Ptf1α/p48 after injury may preclude acinar cell differentiation and appropriate pancreatic regeneration.
Effects of free fatty acids on carbohydrate metabolism and insulin signalling in perfused rat liver
Authors: Anderwald C. , Brunmair B. , Stadlbauer K. , Krebs M. , Fürnsinn C. , Roden M. 
Published: September 2007

AbstractBackground  Elevated circulating free fatty acids (FFAs) induce insulin resistance and play a crucial role in the development of type 2 diabetes, in which fasting hepatic glucose production (HGP) is increased. However, direct effects of FFAs on fasting HGP are still unclear because indirect endocrine and metabolic effects contribute to FFA action. Thus, we aimed to investigate acute direct effects of specific FFAs on fasting HGP, lactate uptake, and insulin signalling.Materials and methods  Isolated livers obtained from 20 h fasted rats were perfused with albumin‐bound palmitate or oleate (200 µmol L−1 each) or vehicle (control) for 180 min (n = 5–7/group).Results  Compared to control, hepatic lactate uptake was increased by palmitate and oleate (~+40%; P < 0·05), while HGP from lactate (~3 mmol L−1) and liver glycogen content were similar. Tyrosine phosphorylation (pY) of insulin‐receptor‐substrate‐(IRS)‐2 and p70S6‐kinase phosphorylation were not affected by FFAs. Palmitate decreased insulin‐receptor‐β pY, IRS‐1 pY and phosphoinositol‐3‐kinase expression by 46 ± 16%, 46 ± 11% and 20 ± 9%, respectively (P < 0·03), while oleate reduced Akt phosphorylation by 85 ± 7% (P < 0·006).Conclusions  Isolated liver perfusion with saturated or unsaturated FFAs reduced insulin signalling protein phosphorylation at different sites and increased lactate uptake without affecting HGP or glycogen content. These results suggest that at fasting, both saturated and unsaturated FFAs increase hepatic glucose precursor uptake and may, independently of insulin's presence, accelerate protein dephosphorylation of the insulin signalling cascade at different sites.
Collagen type VIII expression in human diabetic nephropathy
Authors: Gerth J. , Cohen C. D. , Hopfer U. , Lindenmeyer M. T. , Sommer M. , Gröne H. J. , Wolf G. 
Published: September 2007

AbstractBackground  Collagen type VIII is a non‐fibrillar short‐chain collagen that may modulate migration, proliferation and adherence of various cells. Only very sparse information exists on collagen type VIII expression in human diabetic nephropathy.Material and methods  We retrospectively studied mRNA expression for the two collagen type VIII chains (COL8A1 and COL8A2) in 20 biopsies with histologically confirmed diabetic nephropathy by real‐time PCR, and compared glomerular and tubular expression with normal kidney [pre‐transplant biopsies (n = 10)]. Expression of collagen type VIII was also studied in biopsies from patients with benign nephrosclerosis (BNS; n = 16) and focal‐segmental glomerulosclerosis (FSGS; n = 9).Results  A strong specific induction of COL8A1 mRNA was found in diabetic nephropathy in both glomerular and tubular compartments. There was also a robust induction of COL8A2 in diabetic nephropathy, but overall expression was lower than that of COL8A1 transcripts. No significant increase in COL8A1 and COL8A2 mRNAs expression was found in biopsies from patients with BNS and FSGS compared with normal kidneys. The cross‐reactivity of the used anti‐α1(VIII) antibody with human tissue was confirmed by Western blots. Immunohistological analysis revealed only little staining for collagen type VIII in the normal kidney, localized to vessels. There was an up‐regulation of collagen type VIII protein expression as shown by immunohistochemistry in the diabetic nephropathy biopsies mainly localized to mesangial cells, tubules and the interstitium. Proteinuria and serum creatinine did not correlate with glomerular or tubular COL8A1 and COL8A2 mRNA expression in diabetic patients.Conclusion  Our study systemically investigates collagen type VIII expression in human biopsies. Induction of collagen type VIII was specific for diabetic nephropathy and did not occur in the other renal diseases studied. More specific factors of the diabetic environment are likely involved in the stimulated expression because there was no correlation of collagen type VIII mRNA expression with proteinuria. Since collagen type VIII may influence proliferation and migration of cells, it is possible that an increase in renal expression of collagen type VIII initiates other pathophysiological processes (e.g. proliferation of renal fibroblasts) involved in diabetic nephropathy.
Microalbuminuria and the metabolic syndrome and its components in the Chinese population
Authors: Lin C.‐C. , Liu C.‐S. , Li T.‐C. , Chen C.‐C. , Li C.‐I. , Lin W.‐Y. 
Published: September 2007

AbstractBackground  Microalbuminuria and the metabolic syndrome (MetS) have both been linked to chronic kidney disease and cardiovascular disease. This study investigated the association between urinary albumin‐to‐creatinine ratio (ACR) and MetS and its components.Materials and methods  A total of 2311 subjects aged 40 years and over were recruited in 2004 in a metropolitan city in Taiwan. The biochemical indices, such as fasting glucose levels, urinary albumin, urinary creatinine and anthropometric indices, were measured. We defined microalbuminuria as a urinary ACR ranging from 30 to 300 mg g−1 creatinine. MetS was defined using the American Heart Association and the National Heart, Lung and Blood Institute (AHA/NHLBI) and the International Diabetes Federation (IDF) definitions. The relationship between MetS and microalbuminuria was examined using multiple logistical regression analysis.Results  Subjects with microalbuminuria had higher age, body mass index (BMI), waist circumference, blood pressure, fasting plasma glucose, triglycerides, total cholesterol (TCHOL)/high‐density lipoprotein cholesterol (HDL‐C) ratio, prevalence of diabetes mellitus and hypertension and lower HDL‐C than subjects with normoalbuminuria. After adjusting for age and BMI, microalbuminuria was associated with the individual components of MetS, except in central obesity in women and elevated fasting glucose in men. After adjusting for age, BMI, smoking and alcohol consumption status, multiple logistical regressions revealed that microalbuminuria is strongly associated with MetS in both genders and according to both definitions. The odds ratio of having MetS using the AHA/NHLBI and IDF definition was 1·76 (1·16–2·67) and 1·73 (1·06–2·83) in men and 2·19 (1·38–3·50) and 2·09 (1·24–3·51) in women, respectively.Conclusions  Microalbuminuria was strongly associated with MetS and its components. There is an increased likelihood of having MetS if subjects have microalbuminuria.
Activated Vegfr2/kdr Pathway In Tumour Cells And Tumour Associated Vessels Of Colorectal Cancer
Authors: Giatromanolaki A. , Koukourakis M. I. , Sivridis E. , Chlouverakis G. , Vourvouhaki E. , Turley H. , Harris A. L. , Gatter K. C. ,   for the ‘Tumour and Angiogenesis Research Group’
Published: September 2007

AbstractBackground  Vascular endothelial cell growth factor (VEGF) acts by phosphorylating specific tyrosine kinase receptors on endothelial cell membrane promoting angiogenesis. The study of the activation status of VEGF receptors in human malignancies has recently become feasible by means of specific monoclonal antibodies recognising the phosphorylated form of these receptors.Materials and methods  In the current study, we investigate the expression of the phosphorylated VEGFR2/KDR receptor in normal colon and colorectal adenocarcinomas in parallel with histopathological parameters, prognosis and the expression of the ‘hypoxia inducible factor’ HIF1α.Results  pVEGFR2/KDR was weakly expressed in the normal colon, but it was expressed strongly in the cytoplasm and nuclei of cancer cells and in the tumour associated vasculature, mainly at the invading tumour edge. pVEGFR2/KDR expression in cancer cells was significantly associated with a tumour diameter > 6 cm (P = 0·04), poor histological differentiation (P = 0·004) and with high ÇÉF1α expression (P = 0·05). High pVEGFR2/KDR expressing vascular density was significantly related with a high VEGF and HIF1α expression in cancer cells (P = 0·02 and 0·03, respectively). This was also related significantly to high pVEGFR2/KDR expression in cancer cells. In multivariate analysis, the most significant predictors for death were lympho‐vascular invasion (P < 0·001) followed by VEGF (P = 0·014), node status (P = 0·015), standard vascular density (P = 0·022) and necrosis (P = 0·032).Conclusions  pVEGFR2 receptors are largely expressed in colon cancer cells and intratumoural vasculature. As VEGF targeting agents enter the clinical practice, the role of monoclonal antibodies recognising the phosphorylated form of VEGF receptors as predictors of response to targeted therapies should be sought in clinicopathological trials.
Markers of inflammation and disuse in vastus lateralis of chronic obstructive pulmonary disease patients
Authors: Crul T. , Spruit M. A. , Gayan‐Ramirez G. , Quarck R. , Gosselink R. , Troosters T. , Pitta F. , Decramer M. 
Published: September 2007

AbstractBackground  Disuse and/or local inflammation in the muscle cannot be excluded as potential influences for the decreased muscle force in patients hospitalised due to an acute chronic obstructive pulmonary disease (COPD) exacerbation. This study aims to compare expression levels of markers of disuse (insulin‐like growth factor‐1 (IGF‐I), MyoD and myogenin) and inflammation [interleukin‐6 (IL‐6), IL‐8 and tumour necrosis factor‐alpha (TNF‐α)] in the muscle of hospitalised and stable COPD patients and healthy elderly.Material and methods  Muscle biopsies (m. vastus lateralis) were taken in 14 hospitalised COPD patients (aged 68 ± 8), 11 clinically stable COPD patients (aged 68 ± 9) and seven healthy subjects (aged 70 ± 7) to analyse local mRNA expression levels of IL‐6, IL‐8, TNF‐α, IGF‐I and protein expression levels of IGF‐I, MyoD and myogenin. Relationships of these expression levels with lung and skeletal muscle function were investigated.Results  IGF‐I mRNA and MyoD protein levels were significantly lower in hospitalised patients compared to healthy subjects. MyoD protein levels were positively related to quadriceps force. Muscle IL‐6 and IL‐8 expression in hospitalised patients was similar compared to stable patients and healthy subjects and was not related to expression levels of muscle markers of disuse or quadriceps force. Muscle TNF‐α and myogenin were not detected.Conclusion  Decreased expression levels of muscle IGF‐I and MyoD in hospitalised patients suggest a potential influence of disuse in the increased muscle weakness during an acute COPD exacerbation. This study did not find any evidence supporting local inflammation via IL‐6, IL‐8 and/or TNF‐α in the vastus lateralis muscle of COPD patients.
Hypoxanthine decreases equilibrative type of adenosine transport in lymphocytes from Lesch–Nyhan patients
Authors: Prior C. , Torres R. J. , Puig J. G. 
Published: September 2007

AbstractBackground  Lesch‐Nyhan (LN) syndrome is associated with deficient hypoxanthine‐guanine phosphoribosyltransferase (HPRT) activity, but the connection between the aberrant purine metabolism and the neurological symptoms remains largely unknown. The aim of this study was to determine adenosine transporter subtypes affected by HPRT deficiency and by the associated hypoxanthine excess.Materials and methods  Nucleoside transporter types (depending on their sodium dependence and 10 µm nitrobenzylthioinosine, NBTI, sensitivity) involved in adenosine transport were compared between peripheral blood lymphocytes (PBL) obtained from nine LN patients, PBLLN (2–21 years) and from nine controls, PBLC (2–23 years) under basal conditions and after 25 µm hypoxanthine incubation.Results  We found four types of adenosine transporters in PBL: equilibrative and concentrative transporters that are either sensitive (ENT1 or cs) or insensitive (ENT2 or ci) to NBTI. Adenosine ENT1 uptake was the predominant transporter in both PBLC (55%) and PBLLN (46%). Under basal conditions no significant differences were found in adenosine transport between PBLC and PBLLN. Incubation of PBL with 25 µm hypoxanthine markedly decreased total adenosine transport in both cell types. Hypoxanthine affected equilibrative transport (mainly ENT2 type) in PBLLN and PBLC. Only in PBLC was concentrative transport affected by hypoxanthine. Expressions of human (h) ENT1 and hENT2 mRNA were not significantly modified by hypoxanthine incubation in PBLC.Conclusions  This study contributes to further knowledge of the defective adenosine transport found in PBLLN. Increased hypoxanthine levels, similar to those reported in HPRT deficient patients, reduced adenosine uptake by 32% in PBLLN as compared to normal transport.
Role of soil constituents in fixation of soluble Zn, Cu, Ni and Cd added to soils
Authors: Buekers J. , Van Laer L. , Amery F. , Van Buggenhout S. , Maes A. , Smolders E. 
Published: September 2007

SummarySlow immobilization of trace metals in soil, termed ‘fixation’, affects their natural attenuation but it is still unclear which reactions occur. Twenty‐eight soils were selected to assess the role of Fe oxides and carbonates on fixation of Cu, Cd, Zn and Ni. Soils included samples from 2 toposequences (Vietnam, Spain) and 13 European topsoils with different soil characteristics (pH 3.4–7.7). Samples were amended with 250 mg Zn kg−1, 100 mg Cu kg−1, 80 mg Ni kg−1 and 2.5 mg Cd kg−1 as metal salts and incubated for 850 days. Fixation was measured as the increase of the fraction of added metals that were not isotopically exchangeable. Fixation increased with time and was, averaged over all the soils, 43% (Cu), 41% (Zn), 41% (Ni) and 28% (Cd) after 850 days. Metal fixation within samples from each toposequence was generally positively related to total Fe oxide concentration (Fed) for Zn, Ni and Cd. However, the fixation of Cd, Zn and Ni was mainly explained by pH and not by Fed when considering all soils. Fixation of Zn and Cd in soils with pH >7.0 increased with increasing concentrations of carbonates at initial ageing times. Fixed fractions of Zn, Ni and Cd were significantly released when experimentally removing 50% of carbonates by acidification. Fixation of Cu was most poorly related to soil properties. Our data suggest that fixation of Cd, Zn and Ni is related to a pH‐dependent diffusion into oxides and that of Cd and Zn also to diffusion and/or coprecipitation in carbonates. Fixation of Ni at neutral pH may also be related to stabilization of precipitates that form readily in soil.
Allergic inflammatory reaction is involved in necrosis of human pulmonary dirofilariasis
Authors: Araya J , Kawabata Y , Tomichi N , Kaneko K , Hayashi K , Iwabuchi K , Terasaki Y , Kawashima T , Watanabe M 
Published: September 2007

Aims:  To determine whether, in view of the massive inflammatory cell infiltration and the rounded rather than wedge‐shaped character of pulmonary lesions in dirofilariasis, the inflammatory response against the worm contributes to the coagulative necrosis, in addition to an ischaemic process.Methods and results:  The histopathological features of 13 resected dirofilariasis cases with well‐defined nodules ranged from 10 to 30 mm were analysed. On routine histology and using immunohistochemistry, the peripheral encapsulating wall showed mild to severe infiltration of eosinophils, lymphocytes and plasma cells and a histiocytic reaction in all cases, often with necrotic eosinophils seen within the necrosis (84.6%) and inflammatory changes in the adjacent lung (38.5%). The CD4+ lymphocyte count (80.8 ± 33.4) was greater than that of CD8+ lymphocytes (24.5 ± 16.9) in the central necrosis and vice versa in the wall. In the necrotic regions, disruption of the pulmonary artery (61.5%) and extravasation of the torn worm (23.1%) could be seen.Conclusions:  These findings indicate that an allergic inflammatory reaction, mediated by eosinophils and lymphocytes, is involved in the formation of the dirofilarial necrotizing granuloma rather than infarction caused simply by embolism.
Changes of periodontal parameters following apical surgery: a prospective clinical study of three incision techniques
Authors: Von Arx T. , Vinzens‐Majaniemi T. , Bürgin W. , Jensen S. S. 
Published: September 2007

AbstractAim  To evaluate periodontal changes following apical surgery, and to relate changes to the type of incision and to the type of restoration present at the gingival margin (GM).Methodology  Periodontal parameters [probing depth (PD), level of GM and clinical attachment, plaque and bleeding indices] were recorded at baseline and 1 year following apical surgery. The periodontal changes were calculated and assessed with respect to the incision technique (intrasulcular incision, papilla base incision and submarginal incision), as well as to the presence and type of a restoration margin in contact with the gingiva.Results  One hundred and eighty‐four teeth could be evaluated. No significant differences between the three incision techniques were found regarding changes in PDs and plaque index over time. However, significant differences between the intrasulcular and submarginal incisions were found for changes in levels of GM and clinical attachment. For example, with the intrasulcular incision, there was a mean recession of 0.42 mm at buccal sites, whereas using the submarginal incision there was a gain of 0.05 mm. No statistically significant influence could be demonstrated for the presence and type of restoration margins, or the smoking habit of the patient.Conclusion  The type of incision was found to affect changes significantly in periodontal parameters within an observation period of 1 year following apical surgery, whereas the restoration margin and smoking habit did not prove to have any significant effect.
The origins and time of appearance of focal testicular dysgenesis in an animal model of testicular dysgenesis syndrome: evidence for delayed testis development?
Authors: Hutchison Gary R. , Sharpe Richard M. , Mahood I. Kim , Jobling Matt , Walker Marion , McKinnell Chris , Mason J. Ian , Scott Hayley M. 
Published: September 2007

SummaryA testicular dysgenesis‐like syndrome is induced in rats by fetal exposure to di(n‐butyl) phthalate (DBP). A key feature of this is the formation of focal dysgenetic areas comprising malformed seminiferous cords/tubules and intratubular Leydig cells (ITLC), but how and why these arise remains unclear. The present study has used combinations of cell‐specific markers and immunohistochemistry to address this. The results show that focal dysgenetic areas and ITLC first appear postnatally at 4–10 days of age, but this only occurs in treatment groups in which formation of fetal Leydig cell aggregation is induced between e17.5 and e21.5. Extreme variability in the formation and size of the Leydig cell aggregates probably accounts for the equally extreme variation in occurrence and size of focal dysgenetic areas postnatally. DBP‐induced fetal Leydig cell aggregation traps Sertoli and other cells within the aggregates, but it is unclear why this happens nor why cords fail to form prenatally in these cell mixtures but do elsewhere in the fetal testis. The present studies show that differentiation of the fetal Leydig cells is drastically delayed at e15.5 after DBP exposure, which may be indicative of a wider delay in testis cell development and organisation, and this might account for some of the unexplained findings.