bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atrial natriuretic peptide increases albuminuria in type 1 diabetic patients: evidence for blockade of tubular protein reabsorption.
Authors: Jacobs E. M. G. , Vervoort G. , Branten A. J. W. , Klasen I. , Smits P. , Wetzels J. F. M. 
Published: March 2003

BackgroundIt has been suggested that atrial natriuretic peptide (ANP) contributes to the glomerular hyperfiltration of diabetes mellitus. Infusion of ANP increases the urinary excretion of albumin in patients with type 1 diabetes mellitus (IDDM). Although the increased albuminuria is attributed to a rise in glomerular pressure, alterations in tubular protein handling might be involved.Patients and methodsWe have studied the effects of ANP in nine microalbuminuric IDDM patients. After obtaining baseline parameters, ANP was infused over a 1‐h period (bolus 0.05 μg kg−1, infusion rate 0.01 μg kg−1 min−1). Renal haemodynamics, sodium and water clearance and tubular protein handling were studied.ResultsThe glomerular filtration rate (GFR) increased from 116.4 ± 8.9 to 128.3 ± 8.8 mL min−1 1.73 m−2, whereas the effective renal plasma flow (ERPF) decreased from 534.3 ± 44.3 to 484.9 ± 33.3 mL min−1 1.73m−2 (P < 0.05). As a result, the filtration fraction was significantly higher during infusion of ANP. ANP attenuated proximal tubular sodium reabsorption. Urinary albumin excretion rose from 87.57 ± 21.03 to 291.40 ± 67.86 μg min−1 (P < 0.01). Changes in the urinary excretion of β2‐microglobulin and free κ‐light chains were more marked, the excretion of β2‐microglobulin increasing from 0.28 ± 0.21 to 51.87 ± 10.51 μg min−1 (P < 0.01), and of free κ‐light chains from 4.73 ± 1.74 to 46.14 ± 6.19 μg min−1 (P < 0.01).ConclusionsThe observed rise in albuminuria during infusion of ANP does not simply reflect a change in glomerular pressure, but might at least partly result from an attenuation of tubular protein reabsorption.
Cardiomyocyte apoptosis and progression of heart failure to transplantation
Authors: Saraste  , Pulkki  , Kallajoki  , Heikkilä  , Laine  , Mattila  , Nieminen  , Parvinen  , Voipio‐Pulkki  
Published: March 2003

BackgroundCardiomyocyte apoptosis has been found in congestive heart failure, but its clinical significance has been difficult to study. We compared the occurrence of cardiomyocyte apoptosis in explanted hearts with the progression of severe heart failure until the need for transplantation.DesignUsing the TUNEL assay, apoptotic cardiomyocytes were quantified in explanted failing hearts from patients with either idiopathic dilated cardiomyopathy (n = 21) or ischaemic heart disease (n = 14). The percentage was compared with the clinical severity and progression of end‐stage heart failure. Samples obtained at autopsy and during open heart surgery served as controls.ResultsThe number of apoptotic cardiomyocytes was significantly increased in failing hearts regardless of aetiology (medians 0.075% in ischaemic heart disease and 0.119% in dilated cardiomyopathy) compared with control myocardium. In patients with dilated cardiomyopathy, apoptotic cardiomyocytes were more numerous in subjects with a rapidly deteriorating clinical course (0.192%, n = 10) than in patients with intermediate (0.093%, n = 6, P = 0.03) or slow (0.026%, n = 5, P = 0.003) progression. No such association was observed in patients with ischaemic heart disease, in whom we found significantly increased cardiomyocyte apoptosis adjacent to scars of previous infarctions (0.576%) in contrast to the diffuse distribution seen in dilated cardiomyopathy. Expression of Bcl‐2, an antiapoptotic protein, was increased in all failing hearts by immunohistochemistry.ConclusionCardiomyocyte apoptosis is a consistent feature of end‐stage heart failure in man and appears to be quantitatively related to the clinical severity of deterioration in dilated cardiomyopathy. Increased expression of Bcl‐2 in cardiomyocytes indicates activation of an antiapoptotic response. These observations suggest that cardiomyocyte apoptosis is a clinically relevant and potentially modifiable pathophysiological phenomenon in severe heart failure.
Effect of cholestyramine on bile acid pattern and synthesis during administration of ursodeoxycholic acid in man
Authors: Rust  , Sauter  , Oswald  , Büttner  , Kullak‐Ublick  , Paumgartner  , Beuers  
Published: March 2003

BackgroundCholestyramine is the first‐line treatment for cholestasis‐induced pruritus and is prescribed along with ursodeoxycholic acid (UDCA) in patients with cholestatic liver diseases. Impairment of the intestinal absorption of endogenous hydrophobic bile acids by cholestyramine is well known. It is unclear, however, whether cholestyramine also impairs the absorption of the hydrophilic bile acid, UDCA, in man.AimsTo study serum levels of UDCA and endogenous bile acids as well as endogenous bile acid synthesis during simultaneous or separate administration of UDCA and cholestyramine in vivo; and absorption of UDCA both in the presence and absence of its hydrophobic epimer, chenodeoxycholic acid (CDCA), by cholestyramine in vitro.Patients and methodsFive healthy subjects received UDCA (12.5 ± 0.5 mg kg−1 daily) as a single dose for periods of 14 days with or without cholestyramine (4 g daily). Fasting serum levels of bile acids and of 7α‐hydroxy‐4‐cholesten‐3‐one (α‐HC), a measure of endogenous bile acid synthesis, were determined by gas chromatography and high pressure liquid chromatography, respectively. In vitro, bile acid solutions were incubated for 24 h in the presence or absence of cholestyramine, and bile acid concentrations were determined in the supernatant.ResultsSimultaneous administration of UDCA and cholestyramine in man led to a decrease of fasting serum levels of UDCA by 60% when compared to UDCA serum levels during administration of UDCA alone. In contrast, serum levels of endogenous bile acids were not affected and α‐HC serum levels were found increased 2.7‐fold indicating stimulation of endogenous bile acid synthesis by cholestyramine. Administration of cholestyramine and UDCA at an interval of 5 h tended to diminish the effect of cholestyramine on UDCA serum levels. In vitro, conjugated and unconjugated UDCA were effectively bound by cholestyramine both in the presence and absence of hydrophobic bile acids.ConclusionsThe results strongly support the recommendation to administer UDCA and cholestyramine at different times of day.
Lactose (mal)digestion evaluated by the 13C‐lactose digestion test
Authors: Vonk  , Lin  , Koetse  , Huang  , Zeng  , Elzinga  , Antoine  , Stellaard  
Published: March 2003

BackgroundThe prevalence of genetically determined lactase nonpersistence is based on the results of the lactose H2 breath test. This test, however, is an indirect test, which might lead to misinterpretation.DesignWe determined lactase activity in healthy Chinese and Dutch students using a novel 13C‐lactose digestion test. The cut‐off value of this test was established in a Chinese population with a homogenous genetic background of lactase nonpersistence and was compared with the results obtained in a Caucasian population. Twenty‐five grams of a 13C‐lactose solution was consumed by 12 known H2‐positive and 5 H2‐negative Chinese students and 48 Dutch students and, subsequently, 13C‐glucose concentration in plasma and H2 excretion in breath were measured.ResultsA similar 13C‐glucose response curve was found in all Chinese students. The mean response curve in the Dutch students was more pronounced (P < 0.01). The 1 h (peak) plasma 13C‐glucose concentration was the best discriminator between lactose digesting and maldigesting subjects. The cut‐off level of 2 mmol L−113C‐glucose in plasma was defined in the H2‐positive Chinese students group. Based on the 13C‐glucose response the prevalence of lactose maldigestion in the Dutch subjects was 25%; based on the lactose H2 breath test 17%.ConclusionsUsing the 13C‐lactose digestion test the results demonstrate a higher prevalence of lactose maldigestion in a Caucasian population than indicated by the results of the H2 breath test. A moderate increase in the plasma 13C‐glucose concentration after consumption of 13C‐lactose in the young adult Chinese subjects indicates a residual lactase activity in that age group, even when a positive H2 breath test result is obtained. These results indicate that the 13C‐glucose concentration in plasma more accurately reflects the small intestinal lactose digestion capacity than the lactose H2 breath test.
Expression of keratinocyte growth factor and its receptor in colorectal cancer
Authors: Otte  , Schmitz  , Banasiewicz  , Drews  , Fölsch  , Herzig  
Published: March 2003

Background and aimsThe mesenchymal derived keratinocyte growth factor stimulates growth, differentiation and migration of intestinal epithelial cells. In the human gastrointestinal tract an overexpression of this growth factor has been reported in inflammatory bowel disease and pancreatic cancer. In the present study we investigated expression patterns of keratinocyte growth factor and receptor in normal and neoplastic colonic mucosa and in metastases. Furthermore, biological effects on normal intestinal and colorectal cancer cell lines were determined.Materials and methodsExpression patterns were analysed at the mRNA level by reverse transcription‐polymerase chain reaction (RT‐PCR) and at the protein level by Western blotting. Localization of ligand and receptor in normal intestinal mucosa and cancer tissue was investigated by immunohistochemistry. Mitogenic effects of keratinocyte growth factor were assayed by [3H]thymidine incorporation in normal (Intestine‐407, IEC‐6, IEC‐18) and colorectal cancer cell lines (Colo320, LoVo, SW403, SW707).ResultsmRNA expression of keratinocyte growth factor and receptor was detected in the majority of normal and cancer samples without significant alterations. At the protein level keratinocyte growth factor expression did not differ between normal and malignant specimens, whereas protein expression of the receptor was increased up to twofold in well‐ to moderately differentiated colorectal cancers. DNA synthesis was significantly stimulated by keratinocyte growth factor in all three normal intestinal cell lines, whereas this growth factor did not significantly alter the [3H]thymidine incorporation in the colorectal cancer cell lines.ConclusionKeratinocyte growth factor and its receptor were detected in the majority of samples from normal and neoplastic colonic mucosa, with an overexpression of the receptor seen in the more differentiated tumour samples. Keratinocyte growth factor is a strong mitogen for normal intestinal cells, whereas it is less effective in neoplastic cells.
Lymphocyte responses following open and minimally invasive thoracic surgery
Authors: Leaver  , Craig  , Yap  , Walker  
Published: March 2003

BackgroundImmunosuppression associated with surgery may predispose to increased tumour growth or recurrence. Lymphocytes are central components of the immune network, signalling specific and non‐specific responses in tumour immunosurveillance. This study was therefore designed to compare the effects of minimally invasive and conventional approaches to major thoracic surgery on lymphocyte populations and oxidative activity.Patients and methodsThe effects of conventional and minimally invasive video‐assisted thoracic surgery (VATS) on the numbers and types of circulating lymphocytes and on lymphocyte oxidation were compared in a prospective randomized study of 41 patients undergoing lobectomy for peripheral bronchogenic carcinoma. Blood taken pre‐operatively and on days 2 and 7 post‐operatively was analysed for T (CD4, CD8), B (CD19) and natural killer (NK) (CD56, CD16) cell counts and for lymphocyte oxidative activity. Leucocyte numbers were compared with pre‐surgical values and oxidative rate with healthy donor controls.ResultsLymphocyte counts fell after surgery; VATS was associated with less effect on circulating T (CD4) cells at 2 days and on NK lymphocytes at 7 days post‐surgery. Lymphocyte oxidation was less suppressed in the VATS group 2 days after surgery. In general, post‐surgical changes in key cells of cellular immunity were smaller in the VATS group, and recovery to normal levels was more rapid.ConclusionThe degree of invasiveness of thoracic surgery may influence the extent of immunosuppression in patients undergoing pulmonary lobectomy for pulmonary neoplasm.
β‐adrenoceptor‐stimulated lipolysis of subcutaneous abdominal adipocytes as a determinant of fat oxidation in obese men
Authors: Imbeault  , Tremblay  , Després  , Mauriège  
Published: March 2003

BackgroundTo verify whether an impaired lipolytic capacity of subcutaneous adipocytes may contribute to low rate of fat oxidation.DesignRelationships between adipose tissue lipolysis of subcutaneous (subc) abdominal and femoral isolated adipocytes and respiratory quotient (RQ) were investigated in 20 obese men (age: 44 ± 5 years; means ± SD) studied in a fasting state.ResultsMaximal isoproterenol‐induced lipolysis was greater in subcutaneous abdominal than in femoral fat cells even if glycerol release was corrected for variation in cell surface area (P < 0.01). On the other hand, no regional variation was observed in the adipose cell lipolytic responses to postadrenoceptor agents such as dibutyryl‐cyclic AMP, forskolin and theophylline. Maximal isoproterenol‐induced lipolysis of subc abdominal, but not of femoral adipocytes, was inversely related to RQ (r = − 0.61; P < 0.01) and positively associated to fat oxidation (r = 0.57; P < 0.01). These relationships were independent of possible confounding factors such as fat mass, fat‐free mass, waist girth and subc abdominal adipose tissue accumulation assessed by computed tomography, as maximal isoproterenol‐induced lipolysis of subcutaneous abdominal adipocytes was the only variable retained as a significant predictor of RQ levels (38% of variance) and of fat oxidation (30% of variance).ConclusionThese results suggest that adipose tissue lipolytic activity of subc abdominal adipocytes acts as a determinant of fat oxidation in obese men.
Effect of preoperative prophylaxis with filgrastim in cancer neck dissection
Authors: Wenisch  , Werkgartner  , Sailer  , Patruta  , Krause  , Daxboeck  , Parschalk  
Published: March 2003

BackgroundCancer surgery is known to lead to a deterioration in host defence mechanisms and an increase in susceptibility to infection after operation. Filgrastim enhances important antimicrobial functions of neutrophils including chemotaxis, phagocytosis and oxidative killing mechanisms.MethodsThe effects of additional (all patients received perioperative 3 ′ 25 mg kg−1 cefotiam and 1 ′ 20 mg kg−1 metronidazole) preoperative prophylaxis with filgrastim (5 μg kg−1 12 h prior to surgery plus 5 μg kg−1 0 h prior to surgery) on neutrophil phagocytosis and reactive oxygen radical production and postoperative infections in 24 patients undergoing cancer neck dissection were studied. Phagocytic capacity was assessed by measuring the uptake of fluorescein isothiocyanate‐labelled Escherichia coli and Staphylococcus aureus by flow cytometry. Reactive oxygen generation after phagocytosis was estimated by determining the amount of dihydrorhodamine 123 converted to rhodamine 123, intracellularly.ResultsIn the filgrastim‐treated patients a higher neutrophil phagocytic capacity was seen intraoperatively, and 1–5 days postoperative, but not prior to surgery. Reactive oxygen radical production was significantly higher in filgrastim‐treated patients prior to surgery, intraoperative and postoperative (1–5 days). 2/12 (17%) patients had postoperative infections in the filgrastim group and 9/12 (75%) patients had infections in the placebo group (P < 0.001). In particular, wound infections were recorded more often in the placebo group (1/12 vs. 6/12; P = 0.004).ConclusionWe conclude that filgrastim enhances perioperative neutrophil function and could be useful in the prophylaxis of postoperative wound infections in patients undergoing cancer neck dissection.
Mannose‐binding lectin promoter and structural gene variants in sarcoidosis
Authors: Foley  , Mullighan  , McGrath  , Pantelidis  , Marshall  , Lympany  , Welsh  , Du Bois  
Published: March 2003

BackgroundSarcoidosis is a chronic granulomatous disease of unknown aetiology. Studies have suggested that the causative agent may be an infectious micro‐organism. The mannose binding lectin (MBL) is involved in innate immunity to a wide range of micro‐organisms. Mutations in the promoter region and exon 1 of the MBL gene occur with high frequency and are associated with reduced serum levels of MBL and increased susceptibility to microbial diseases. This study investigated whether MBL variants predispose to sarcoidosis by increasing their susceptibility to micro‐organisms.MethodsMBL gene promoter and exon 1 variants were detected by sequence specific primer polymerase chain reaction (SSP‐PCR) in 167 UK Caucasian sarcoidosis patients and 164 control subjects. Severity of pulmonary disease outcome among patients was assessed by radiography after a minimum of 4 years from disease onset and classified as mild, moderate, and severe disease categories, accordingly.ResultsMBL variant frequencies were similar in patients and controls studied. Among sarcoidosis patients, the frequencies of variants were similar regardless of severity of disease outcome. The average patient ages at time of diagnosis were similar for all MBL genotypes.ConclusionsMBL gene variants do not appear to influence susceptibility to sarcoidosis, age of disease onset, or severity of disease.
The expression of OX40 in immunologically mediated diseases of the gastrointestinal tract (celiac disease, Crohn's disease, ulcerative colitis)
Authors: Stüber  , Büschenfeld  , Lüttges  , Von Freier  , Arendt  , Fölsch  
Published: March 2003

BackgroundThe membrane bound receptor OX40 (CD134) — a member of the TNF‐R/NGF‐R superfamily — is expressed on activated CD4+‐T cells in humans and rodents. The interaction of OX40 with its ligand (OX40L) has been shown to be important in T‐cell dependent B cell‐stimulation and T‐cell costimulation in vitro and in vivo. Several studies in experimental animal models for immunologically mediated GI‐diseases have stressed the important role of the OX40–OX40L interaction for their manifestations. To assess if the OX40–OX40L interaction is also crucial in the pathogenesis of immunologically mediated diseases of the human gastrointestinal tract (e.g. celiac disease, Crohn's disease, ulcerative colitis) we investigated, in a first line of experiments, the expression of OX40 in biopsy specimens of patients suffering from these diseases.MethodsThe biopsies were formalin fixed and paraffin‐embedded and cut into 5 μm slides. To demask the antigen, the slides were consecutively cooked in citrate buffer for 20 min. Binding of anti‐OX40 antibody was detected using the alkaline phosphatase‐anti‐alkaline phosphatease (APAAP) method.ResultsNine of 11 biopsy specimens of patients with celiac disease were OX40‐positive; none of the 20 control duodenal biopsies demonstrated OX40‐positivity; and all biopsies of patients with ulcerative colitis (n = 11) or Crohn's disease (n = 11), respectively, stained positively for OX40. One of the 20 control biopsies showed OX40 staining.DiscussionOX40 is highly expressed in the gastrointestinal tissue of patients with immunologically mediated bowel diseases. Together with previous studies in animal models for these diseases, the present results point to a potential role of OX40 in their pathogenesis.
Phenylalanine inhibition of the phosphorylation of cytoskeletal proteins from cerebral cortex of young rats is prevented by alanine
Authors: Carreras  , De Mattos‐Dutra  , Meirelles  , Da Rocha  , Wannmacher  , Pessoa‐Pureur  
Published: March 2003

BackgroundPhenylalanine has been considered the main responsible agent for the brain damage that occurs in phenylketonuria.Methods and ResultsIn this work we studied the effect of this amino acid on the in vitro phosphorylation of cytoskeletal proteins of the cerebral cortex of rats. We observed that 2 mM phenylalanine, a concentration usually found in the plasma of phenylketonuric patients, decreased the in vitro32P incorporation into these proteins. In addition, we investigated the effect of alanine on the inhibition of 32P incorporation into cytoskeletal proteins caused by phenylalanine. We observed that 0.5 m
m alanine did not alter 32P incorporation but prevented the inhibition provoked by phenylalanine.ConclusionIn case the inhibition of cytoskeletal protein phosphorylation by phenylalanine also occurs in human phenylketonuria, it is possible that alanine supplementation to the phenylalanine‐restricted diet may be beneficial to these patients.
[11C]Hyaluronan uptake with positron emission tomography in liver disease
Authors: Lindqvist  , Westerberg  , Bergström  , Torsteindottir  , Gustafson  , Sundin  , Lööf  , Långström  
Published: March 2003

BackgroundA hyaluronan‐loading test has been developed for assessment of hyaluronan kinetics and applied in patients with liver and joint diseases. This test describes the metabolic process of hyaluronan but cannot define the specific contribution of different organs. A method for labelling of hyaluronan with the short‐lived positron‐emitting radionuclide 11C has been published and in this study applied in healthy subjects and liver diseases.Materials and methodsPositron emission tomography (PET) was used for the regional assessment and quantification of [11C]hyaluronan uptake in three healthy subjects, four patients with alcoholic liver cirrhosis, one with alcoholic hepatitis and one with liver steatosis. After intravenous administration of 60 MBq of 11C‐labelled hyaluronan, a 55‐min PET scan was performed over the liver and plasma radioactivity was analysed. Rate constants describing the transport of the [11C]hyaluronan tracer from plasma to the liver were calculated.ResultsHigh uptake was observed in the liver combined with a rapid elimination of tracer from plasma. The liver uptake rate (k1) was significantly lower in patients (0.018 min−1) than in healthy subjects (0.043 min−1, P = 0.002). The rate constants seem to be related to the severity of the disease as defined by the Child–Pugh score.ConclusionsThe study suggests that PET with [11C]hyaluronan could be an accurate method by which to assess liver dysfunction, in conditions where endothelial cell function is impaired. The possibility of quantification over extended portions of the body also opens up possibilities to explore regional differences in liver function and to assess other elimination routes of hyaluronan.