Biomedical subjects

W Stremmel

Publications and source records attributed to W Stremmel.

At least 73 records · Page 4Linked to original sources

PubMed2000

Sodium, hydrogen exchange type 1 and bile ductular secretory activity in the guinea pig.

Biliary epithelial cells (BECs) express different Na(+), H(+) exchange (NHE) isoforms. In this study, the potential role of NHE in ductular bile secretion is assessed. Experiments were performed in guinea pig perfused livers and isolated BECs. Inhibition of NHE was achieved by hypotonic stress and by using the unspecific NHE inhibitor, amiloride, or the specific NHE 1 inhibitor, cariporide (HOE 642). Hypotonic stress inhibited basal bile flow by 46% and prevented secretin stimulation of bile flow by reducing biliary bicarbonate output by 50%. Secretin increased bile flow from 3.7 +/- 0.8 microL/min/g to 4.78 microL/min/g (P <.01); subsequent exposure to hypotonic stress decreased secretin-stimulated bile flow by 35% and biliary bicarbonate secretion by approximately 50%. Inhibition of NHE by amiloride or cariporide resulted in a similar reduction of secretin-stimulated bile flow and bicarbonate secretion. Basal bile flow was unaffected by the NHE inhibitors. In isolated guinea pig BECs, regulatory volume decrease and inhibition of NHE was demonstrated after hypotonic stress under basal and secretin-stimulated conditions. In contrast, hypotonic exposure inhibited Cl(-), HCO(3)(-) exchange activity in isolated BECs only during basal conditions but incompletely after secretin stimulation. Our study shows that hypotonic stress inhibits basal bile flow in the guinea pig by inhibition of Cl(-), HCO(3)(-) exchange. NHE1 is not involved in basal bile formation. Increased choleresis after ductular stimulation by secretin depends on intact NHE1 activity. These data indicate that BEC volume changes have profound effects on biliary secretory function.

Amiloride↗

PubMed2000

Seropositivity for MIA and S100 in patients with gastrointestinal carcinomas.

Serum levels of melanoma inhibiting activity (MIA) and S100, both markers in malignant melanoma, are increased only in few patients with non-melanocytic tumors. We examined a series of serum samples from patients with colorectal (CRC) (N=56), gastric (GC) (N=43), pancreatic (PC) (N=29), hepatocellular (HCC) (N=30), cholangiocellular and gallbladder carcinoma (CCC) (N=18). MIA and S100 were measured by commercially available assays. Positive serum levels for MIA and S100 were found in 16.1% and 5.4% of the patients with CRC, 11.6% and 9.3% with GC, 34.5% and 13.8% with PC, 0% and 30% with HCC and 16.7% with CCC, respectively. All patients with sera positive for either MIA or S100 suffered from advanced tumors and received palliative treatment. Elevated serum levels of MIA and S100 are frequent in patients with gastrointestinal cancer. Further investigation is warranted to define the role of MIA or S100 seropositivity in gastrointestinal cancer with regard to follow-up.

Adult↗

PubMed2000

[Standardized morphology-adjusted resection in treatment of benign nodular struma].

In 1996 we performed a prospective study with 279 patients suffering from benign nodular goiter. The study investigates the influence of a standardized morphologically adjusted resection technique--SMART--on complication rates in surgery. Apart from the number of transient and permanent recurrent laryngeal nerve lesions and hypocalcemia, we focused in particular on the rate of "false relapses" associated with residual nodular tissue after resection. Bilateral ligation of the inferior thyroid artery in a bilobal approach as well as the entire preparation towards the ligament of Berry permit a reduction in irreversible nerve lesions in all lobal resections to 0.4% and permanent hypocalcemia to 0.3%. Bilateral ligation of the inferior thyroid artery results in a significantly larger number of transient hypocalcemia, without any impact on the long-term course. By applying a standardized surgical technique, a residual nodular goiter rate of 1.4% can be achieved. In spite of thorough intraoperative exploration, false relapses cannot completely be ruled out, however. Nodular tissue might remain undetected by conventional intraoperative exploration even in the presence of sophisticated preoperative ultrasound of the thyroid gland. Also, performing an enucleation can lead to remaining nodules, particularly in the posterior areas. For the future intraoperative ultrasound may be an interesting method in these doubtful cases.

Diagnosis, Differential↗

PubMed2000

Functional interactions between oxidative stress, membrane Na(+) permeability, and cell volume in rat hepatoma cells.

BACKGROUND & AIMS: Oxidative stress leads to a rapid initial loss of liver cell volume, but the adaptive mechanisms that serve to restore volume have not been defined. This study aimed to evaluate the functional interactions between oxidative stress, cell volume recovery, and membrane ion permeability. METHODS: In HTC rat hepatoma cells, oxidative stress was produced by exposure to H(2)O(2) or D-alanine plus D-amino acid oxidase (40 U/mL). RESULTS: Oxidative stress resulted in a rapid decrease in relative cell volume to 0.85 +/- 0.06. This was followed by an approximately 100-fold increase in membrane cation permeability and partial volume recovery to 0.97 +/- 0.05 of original values. The volume-sensitive conductance was permeable to Na(+) approximately K(+) >> Tris(+), and whole-cell current density at -80 mV increased from -1.2 pA/pF at 10(-5) mol/L H(2)O(2) to -95.1 pA/pF at 10(-2) mol/L H(2)O(2). The effects of H(2)O(2) were completely inhibited by dialysis of the cell interior with reduced glutathione, and were markedly enhanced by inhibition of glutathione synthase. CONCLUSIONS: These findings support the presence of dynamic functional interactions between cell volume, oxidative stress, and membrane Na(+) permeability. Stress-induced Na(+) influx may represent a beneficial adaptive response that partially restores cell volume over short periods, but sustained cation influx could contribute to the increase in intracellular [Na(+)] and [Ca(2+)] associated with cell injury and necrosis.

Alanine↗

PubMed2000

Downregulation of ileal bile acid absorption in bile-duct-ligated rats.

BACKGROUND/AIMS: Accumulation of toxic bile acids in cholestasis contributes to liver injury and depends on their synthesis, secretion and intestinal absorption. In the present study, we investigated the effect of cholestasis on the active ileal absorption of bile acids in vivo and the adaptation of transporters involved in ileal bile acid absorption. METHODS: Male Wistar rats underwent ligation of the common bile duct or biliary diversion. Sham-operated rats served as controls. Active ileal bile acid absorption of taurocholate was measured by an intestinal perfusion technique. Transporter mRNA levels of the Na+/bile acid cotransporting protein (IBAT), ileal lipid binding protein (ILBP) and organic anion transporter subtype 3 (Oatp3) and protein expression of IBAT and ILBP were determined in the distal ileum. RESULTS: After bile duct ligation the intestinal absorption rates of taurocholate were lower (p<0.05) and after biliary diversion absorption rates were higher compared to sham-operated animals (p<0.05). The absorption rates were inversely correlated to serum bile acid concentrations. Levels of IBAT-, ILBP- and Oatp3- mRNA were not different between the groups. However, in cholestatic rats, the expression of the 99-kDa dimer of IBAT was decreased compared to controls (p<0.05), whereas the 46-kDa monomeric protein of IBAT and the expression of ILBP was unchanged. After biliary diversion a similar pattern of protein expression was observed, despite an increased absorption rate. CONCLUSIONS: Cholestasis leads to a decreased active ileal absorption of taurocholate. The changes in protein expression may not account for the different absorption rates. The intestinal absorption of bile acids seems to be regulated by their systemic concentration.

Animals↗

PubMed2000

Serum thrombomodulin-a reliable marker of disease activity in systemic lupus erythematosus (SLE): advantage over established serological parameters to indicate disease activity.

To date no specific serological parameter is available to assess disease activity in SLE. Soluble serum thrombomodulin is a new marker of endothelial cell injury and vasculitis. The objective of this study was to compare in vivo soluble thrombomodulin as marker of disease activity in SLE with established and recent serological parameters. One hundred and twenty-four sera of 30 patients with proven SLE with different disease activities were tested for serum levels of thrombomodulin, intercellular adhesion molecule-1 (ICAM-1), E-selectin, vascular cell adhesion molecule-1 (VCAM-1), IL-2R, IL-6, IL-10, dsDNA by ELISA and dsDNA additionally by radioimmunoassay (RIA). C-reactive protein (CRP), complement component C3, IgG, creatinine, anti-nuclear antibodies (ANA) and intermediate filament antibodies were measured by standard laboratory tests. The clinical disease activity was evaluated by the Systemic Lupus Activity Measure (SLAM). Correlations of the different serological SLE disease activity parameters with the SLAM scores revealed the highest significance for serum thrombomodulin (correlation coefficient 0.82). This was further confirmed by the intra-individual analysis of follow-up sera. In addition, a moderate correlation could be found for IL-6, IL-10, ICAM-1, CRP and erythrocyte sedimentation rate (ESR). In summary, soluble thrombomodulin is the most important serological parameter of disease activity in SLE currently available, as shown by the in vivo studies. Soluble thrombomodulin might be a valuable serological parameter for therapeutical considerations.

Adolescent↗

PubMed2000

Interaction of endothelial cells and neutrophils in vitro: kinetics of thrombomodulin, intercellular adhesion molecule-1 (ICAM-1), E-selectin, and vascular cell adhesion molecule-1 (VCAM-1): implications for the relevance as serological disease activity markers in vasculitides.

Recently markers of endothelial cell activation or injury gained increasing interest as serological parameters of disease activation in vasculitides. Among these, soluble serum thrombomodulin, ICAM-1, VCAM-1 and E-selectin are of particular interest. However, only thrombomodulin showed the expected close correlation. The objective of this study was to investigate in vitro the kinetics of these endothelial cell receptors after interaction of unstimulated or cytokine-activated polymorphonuclear neutrophils (PMN) and endothelial cells in order to find evidence explaining these different clinical findings. Over the time period of up to 48 h of incubation the kinetics of thrombomodulin, ICAM-1, E-selectin, and VCAM-1 levels in the supernatant of endothelial cells in co-culture with neutrophils were determined in vitro by ELISA under basal and partially cytokine-activated (tumour necrosis factor-alpha) conditions. Increased levels of ICAM-1, E-selectin and VCAM-1 were already found due to cytokine activation of endothelial cells alone. This increase was augmented after coincubation with neutrophils. In contrast, a significant increase of thrombomodulin in the supernatant was only found due to cell injury after cell-cell interaction of cytokine-activated endothelial cells with neutrophils. In conclusion, this in vitro model of the kinetics of soluble endothelial cell receptors after cell-cell interaction of cytokine-activated PMN and endothelial cells underlines the advantage of thrombomodulin in contrast to the adhesion molecules as a marker of endothelial damage. Therefore, soluble thrombomodulin seems to be a promising, valuable serological disease activity marker in vasculitides.

Autoimmune Diseases↗

PubMed2000

Effect of tauroursodeoxycholic acid on bile acid-induced apoptosis in primary human hepatocytes.

BACKGROUND/AIMS: The accumulation of endogenous bile acids contributes to hepatocellular damage during cholestatic liver disease. To evaluate the potential role of apoptotic cell death due to increased concentrations of bile acids, primary human hepatocytes were treated with hydrophobic and hydrophilic bile acids. Because the Fas receptor-ligand system may mediate apoptosis in human liver cells, the effect of toxic bile acids on hepatocellular Fas receptor expression was evaluated. MATERIALS AND METHODS: Primary human hepatocytes were incubated with 50 and 100 microM glycochenodeoxycholic acid (GCDCA) and co-incubated with equimolar concentrations of tauroursodeoxycholic acid (TUDCA). To evaluate cytolytic and apoptotic effects, morphological alterations, hepatocellular enzyme release, nuclear DNA fragmentation and hepatocellular Fas receptor expression were evaluated. RESULTS: Apoptotic cell death was significantly increased after exposure to 50 microM GCDCA. Bile acid-induced apoptosis was not accompanied by hepatocellular Fas receptor overexpression. Tauroursodeoxycholic acid reduced apoptosis, as indicated by a significant reduction of oligonucleosomal DNA cleavage. Fas receptor expression was not significantly affected by tauroursodeoxycholic acid. At higher concentrations, direct cytolytic cell destruction was observed. CONCLUSION: Primary human hepatocytes represent a suitable model to study bile acid-induced apoptotic cell death. In these hepatocytes, already low bile acid concentrations might induce apoptotic cell death, which is not triggered by hepatocellular Fas receptor overexpression. Apoptotic DNA fragmentation was significantly reduced by co-incubation with tauroursodeoxycholic acid. The reduction of bile acid-induced apoptosis by ursodeoxycholic acid and its conjugates may contribute to the beneficial effects of these hydrophilic bile acids used for medical treatment of several cholestatic liver diseases.

Apoptosis↗

PubMed2000

[Pulmonal sarcoidosis: A rare side effect of interferon-alpha treatment for chronic hepatitis C infection].

This is a case report of a 44-year-old woman who received a 1-year-treatment with interferon-alpha for chronic hepatitis C virus infection. 3 months after cessation of the therapy she relapsed and was successfully retreated 12 months with a combination of interferon-alpha and ribavirin thereafter. During the treatment the patient developed a typical flue-like syndrome, dry cough with exertional dyspnea that was initially interpreted as a typical side effect of interferon-alpha treatment. Due to the persisting cough, further radiologic and histologic work up was done and results were significant for interstitial sarcoidosis. After interferon-treatment was stopped the pulmonary symptoms resolved completely while pathologic changes in radiographic imaging persisted. Interferon-alpha may have contributed to the development and progression of sarcoidosis by activation of cellular immunity. Although there are only few reports about pulmonary sarcoidosis associated with interferon-alpha treatment, this entity should be included in the differential diagnosis of putative side effects of interferon-alpha therapy.

Adult↗

PubMed2000

[Ulcers of the colon in association with nonsteroidal anti-inflammatory drugs (NSAID)--a rare cause of gastrointestinal bleeding? Report of 3 cases].

Although adverse side effects of nonsteroidal anti-inflammatory drugs (NSAID) can affect the whole gastrointestinal tract, most reports refer to upper gastrointestinal tract complications. We report on 3 patients with lower gastrointestinal bleeding (patient 1 and 2) respectively detectable fecal blood loss (patient 3) after the use of NSAID. Patient 1 and 3 were taking NSAID over at least 6 months for the treatment of rheumatic diseases while patient 2 reported a single use of 2 g acetylsalicylic acid. Colonoscopy showed a single ulcer of the colon in patients 1 and 2. Due to acute bleeding patient 1 required interventional endoscopic treatment. Colonoscopy of patient 3 revealed multiple colonic ulcerations. Gastroduodenoscopy also detected adverse NSAID-effects on the upper gastrointestinal tract in patient 1 and 3 (ulcers of the stomach, erosive duodenitis). NSAID-medication was discontinued in all patients and, additionally, mesalazine was administered to patient 3. Consecutively, symptoms and lesions disappeared. Our cases stress the clinical importance of NSAID-toxicity distal to the small intestine which may exist concomitantly to lesions of the upper gastrointestinal tract and is not obligatory dose-dependent.

Aged↗

PubMed2000

Chemotherapy with gemcitabine in patients with advanced gallbladder carcinoma.

BACKGROUND: Advanced or metastatic gallbladder carcinoma is regarded not much sensitive to chemotherapy. Standard chemotherapy regimens have not been established up to now. PATIENTS: We report on 5 patients with advanced gallbladder carcinoma who received chemotherapy with gemcitabine. RESULTS: Of these 5 patients, 3 demonstrated a partial remission and stable disease was achieved in another patient. Only one patient had no benefit from treatment with gemcitabine. CONCLUSION: We conclude that gemcitabine may be an effective drug in the palliative treatment of gallbladder cancer, and thus its efficiency warrants evaluation in further studies.

Aged↗

PubMed2000

Spontaneous regression of intrahepatic lesions mimicking metastatic disease.

This is a case report of a 53-year-old male with chronic hepatitic C infection presenting with weight loss and elevated liver function tests. Repeated ultrasonography, computed tomography and magnet resonance imaging showed multiple intrahepatic lesions suggestive of metastatic disease. Repeated ultrasound-guided biopsies from the lesions as well as from the adjacent normal appearing liver tissue revealed no malignancy but showed inflammation and significant fibrotic tissue, consistent with chronic hepatitis C. 2 years after the first admission liver function tests were all within the normal range and remained so until today. Computed tomography at that time showed complete remission of all intrahepatic lesions. The exact diagnosis remained elusive but the rare case of reversible focal fibrosis is the most likely cause of these spontaneously regressive lesions.

Diagnosis, Differential↗

PubMed2000

The hepatic microvascular responses to sepsis.

The liver is believed to play a major role in the initiation of multiorgan failure, the most lethal complication in the clinical course of sepsis. Microbes and their virulence factors enter the hepatic circulation where they first activate sinusoidal endothelial cells and Kupffer cells to produce proinflammatory mediators, including TNF-alpha, IL-1, IL-6, reactive oxygen metabolites, and eicosanoids. These mediators cause not only microbial killing, but also structural and functional liver damage concerning mainly the parenchymal cells. Leukocytes are targeted to the liver sinusoids by chemoattractants and, like platelets, tether to the sinusoidal endothelial cells, which are in a procoagulant state of inflammatory activation. Clogging of the sinusoids by these cells leads to a decrease of blood flow through the sinusoids, which is further aggravated by endothelin-1 effectuating the constriction of hepatic stellate cells in the sinusoids. In contrast, both nitric oxide (NO) and carbon monoxide (CO) act as antagonists of endothelin-1 by mediating relaxation of sinusoidal vessels. By maintaining an adequate sinusoidal perfusion, both NO and CO are hepatoprotective during the early, hyperdynamic phase of sepsis characterized by an increased cardiac output and moderate peripheral vasodilation. However, during the late, hypodynamic phase of sepsis, massive overproduction of NO by the inducible NO synthase leads to circulatory collapse, which inevitably includes breakdown of the liver circulation.

Endothelium, Vascular↗

PubMed2000

Helicobacter pylori vacA genotypes and cagA gene in a series of 383 H. pylori-positive patients.

BACKGROUND: Only 10-15% of all patients infected with Helicobacter pylori develop peptic ulcer disease (PUD) or gastric cancer. Apart from immunological factors in the host, virulence determinants of H. pylori such as the vacuolating cytotoxin (VacA) or the cytotoxin-associated protein A (CagA) might represent a predisposition for the development of PUD. METHODS: We studied antral biopsies of 383 H. pylori-positive patients with peptic ulcer disease (PUD) or other H. pylori-related diseases for H. pylori vacA genotypes and the presence of the cagA gene by PCR. RESULTS: VacA genotypes and cagA status could be completely determined in 357 (93.2%) of the patients. In 91 (93.8%) of 97 patients with PUD, the vacA s1 genotype (s1m1, 45; s1m2, 46 patients) was present. The vacA s2m2 genotype was found in only 6 (6.2%) of 97 patients with PUD. In contrast, 180 (75.3%) of 239 patients (s1m1, 89; s1m2, 91 patients) without PUD and without gastric malignancies harbored strains with the vacA s1 genotype. The vacA genotype s2m2 was found in 59 (24.7%) of these patients. The presence of the cagA gene was closely associated with the vacA genotype s1 and found in 124 (88.6%) and in 113 (80.7%) of patients with the s1m1 or s1m2 genotypes, respectively, whereas strains with the genotype s2m2 were almost exclusively cagA negative. CONCLUSION: Most H. pylori strains found in patients with PUD possess the vacA s1 genotype and the cagA gene. Patients with this type of H. pylori strain but without PUD might be at higher risk of developing PUD. In contrast, the risk for PUD might be significantly decreased in those patients who are infected by H. pylori strains with the vacA s2 genotype lacking the cagA gene.

Adult↗

PubMed2000

Extrapulmonary sarcoidosis primarily diagnosed in the liver.

Sarcoidosis is a relatively common, chronic, multisystem disease of unknown origin characterized by the presence of noncaseating epithelioid granulomas. Although an array of organs may be affected by the disease, the commonest site of affection is the lung. We describe a 73-year-old patient admitted to our hospital because of fatigue, weight loss, and an increased alkaline phosphatase level. In conjunction with clinical presentation, laboratory variables, and imaging analysis, a liver biopsy finally confirmed the diagnosis of a systemic sarcoidosis without affection of the lung or mediastinal lymph nodes. Treatment with ursodeoxycholic acid before diagnosis did not improve clinical symptoms and cholestasis indicators. After prednisone treatment, liver enzyme values normalized and remained normal during follow-up for 2 years after diagnosis. The literature on hepatic manifestation of sarcoidosis, its diagnosis, treatment, and prognosis is reviewed. This single case of sarcoidosis presented to the clinician almost exclusively with liver enzyme abnormalities. The consideration of sarcoidosis in such cases is of utmost importance, since the differential diagnosis of hepatic granulomas includes infectious diseases in which treatment with corticosteroids could be fatal.

Aged↗

PubMed2000

Hepatic iron overload in aceruloplasminaemia.

We report the case of a 52 year old male with diabetes mellitus and long standing evidence of hepatic iron excess. Initially considered to have haemochromatosis, this patient was reevaluated when hepatic iron stores were found to be unaffected by a prolonged course of weekly phlebotomy. The development of neurological disease prompted diagnostic consideration of aceruloplasminaemia, which we confirmed by demonstration of a novel frameshift mutation in the ceruloplasmin gene. Our inability to resolve the patient's iron overload by regular phlebotomy is consistent with recent animal studies indicating an essential role for ceruloplasmin in cellular iron efflux. Evaluation of this case underscores the clinical relevance of aceruloplasminaemia in the differential diagnosis of hepatic iron overload and provides insight into the pathogenetic mechanisms of hepatocellular iron storage and efflux.

Ceruloplasmin↗

PubMed1999

HFE downregulates iron uptake from transferrin and induces iron-regulatory protein activity in stably transfected cells.

Hereditary hemochromatosis (HH) is a common autosomal-recessive disorder of iron metabolism. More than 80% of HH patients are homozygous for a point mutation in a major histocompatibility complex (MHC) class I type protein (HFE), which results in a lack of HFE expression on the cell surface. A previously identified interaction of HFE and the transferrin receptor suggests a possible regulatory role of HFE in cellular iron absorption. Using an HeLa cell line stably transfected with HFE under the control of a tetracycline-sensitive promoter, we investigated the effect of HFE expression on cellular iron uptake. We demonstrate that the overproduction of HFE results in decreased iron uptake from diferric transferrin. Moreover, HFE expression activates the key regulators of intracellular iron homeostasis, the iron-regulatory proteins (IRPs), implying that HFE can affect the intracellular "labile iron pool." The increase in IRP activity is accompanied by the downregulation of the iron-storage protein, ferritin, and an upregulation of transferrin receptor levels. These findings are discussed in the context of the pathophysiology of HH and a possible role of iron-responsive element (IRE)-containing mRNAs.

Down-Regulation↗

PubMed1999

[Flu-like infection and liver disease after a stay in the tropics].

HISTORY AND ADMISSION FINDINGS: A 38-year-old patient, an experienced traveller to the tropics, fell ill with a flu-like infection, a fever of up to 38.6 degrees C and nausea on returning from an 8-week trip to southern Africa (Namibia, Zambia and Zimbabwe). Physical examination was unremarkable, except for slight physical debility. His father had died of liver cirrhosis of unknown aetiology, aged 68 years. INVESTIGATIONS: Laboratory tests revealed eosinophilia (12% on a count of 7,800 WBC/microliter, increased transaminase activities [SGPT 142 U/l, SGOT 50 U/l, gamma GT 32 U/l], slightly increased serum ferritin [1057 ng/dl], but normal serum iron and transferrin levels). Untreated stool contained Schistosoma mansoni eggs. Tests for a haemochromatosis gene and its type showed a homozygotic C282Y variant. Liver biopsy demonstrated chronic portal hepatitis with parenchymal transformation and marked haemosiderin deposits in liver epithelium. DIAGNOSIS, TREATMENT AND COURSE: The schistosomiasis was treated with praziquantel, 40 mg/kg by mouth on one day, divided in three doses, without complication. The haemochromatosis was treated symptomatically, at first by weekly bloodletting 500 ml while monitoring serum ferritin concentration. Life-long bloodletting at longish intervals is anticipated. CONCLUSIONS: The incidence of some infectious diseases has greatly risen as a result of an increase in tourism to distant lands. In particular, the diagnosis of frequent parasitic diseases should become part of the expertise in internal medicine. The combination of several diseases should be considered in the differential diagnosis.

Adult↗