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Biomedical subjects

A Holstege

Publications and source records attributed to A Holstege.

102 records · Page 6Linked to original sources
PubMed1981

Inhibition of tyrosine aminotransferase induction by UTP deficiency and its reversal by 5-fluorouridine in cultured hepatoma cells.

Hepatoma tissue culture cells, grown in the presence of D-galactosamine and 6-azauridine, demonstrate a strong reduction of the intracellular UTP pool that can be replenished by formation of UTP from uridine and FUTP from 5-fluorouridine within 2 h. Concomitantly with the UTP deficiency, a decrease of dexamethasone-induced tyrosine aminotransferase activity occurs. 5-Fluorouridine, as compared to uridine, is even more efficient in restoring the activity of tyrosine aminotransferase. Treatment of the cells with D-galactosamine alone results in a minor lowering of UTP that is not followed by the inhibition of the enzyme induction. However, the administration of D-galactosamine, simultaneously or at any time up to 5 h before or after dexamethasone, leads to a 1.5- to 2-fold higher induction (superinduction) which appears 24 h later.

Animals↗
PubMed1981

[Approaches to a selective chemotherapy of hepatocellular carcinoma (author's transl)].

1. An improvement of the chemotherapy of hepatocellular carcinoma with adriamycin or 5-fluorouracil and a reduction of side effects has been achieved by intra-arterial administration of the drugs. This treatment provides a somewhat extended survival but no cure. 2. The treatment of hepatocellular carcinoma in patients by reduction of an inactive precursor of a cytocidal alkylating agent by azoreductase of the tumor showed no therapeutic effect. 3. A selective hepatocellular uptake of drugs coupled to asialoglycoproteins has been described. An application of this concept for the chemotherapy of hepatocellular carcinoma seems doubtful since a loss of binding proteins for desialylated glycoproteins during experimental hepatocarcinogenesis has been demonstrated. 4. The increased uptake of 5-fluorouridine in hepatomas after induction of a tissue-specific depletion of uridine 5'-triphosphate and cytidine 5'-triphosphate provides an effective experimental chemotherapy with limited side effects. A clinical use of this new concept for the chemotherapy of hepatocellular carcinoma may serve as a useful approach.

Antineoplastic Agents↗
PubMedDate not supplied

Cytokines and the liver in health and disease. Effects on liver metabolism and fibrogenesis.

The liver is the largest organ in the body providing a large number of essential functions for the organism. It is the center for the metabolism of nutrients and drugs, and plays a key role in the unspecific immune system by harbouring Kupfer cells, the majority of all macrophages. The liver is the main site for the synthesis of many different metabolites and releases most of the plasma proteins. All these functions of the liver must be coordinated and regulated in response to metabolic changes and minor or major injuries. This is accomplished by metabolites, the autonomous nerve system, the endocrine system and by cytokines, which form a complex network of mediator molecules. Cytokines modulate liver metabolism in many ways. Synthesis of acute phase proteins is regulated by cytokines such as IL-1, IL-6, IL-11, leukemia inhibitory factor, TNF, transforming growth factor beta, epidermal growth factor, and ciliary derived neurotropic factor, which interact synergistically with corticosteroids and insulin. Hepatic lipid metabolism and hepatic carbohydrate metabolism are also regulated by cytokines and by classical hormones. Cytokines play an important role in the pathogenesis of liver diseases and liver fibrosis, which is the common morphological reaction after chronic injury of the liver. An uncontrolled production of extracellular matrix and its impaired degradation destroy the architecture of the liver and its function. Fat-storing cells (Ito cells, lipocytes, perisinusoidal cells) are the major source of extracellular matrix in the liver. They are activated to proliferate or to produce extracellular matrix compounds by cytokines like transforming growth factor beta, and platelet derived growth factor (PDGF). Interferon gamma and alpha inhibit this activation. Modulation of fibrogenesis by these cytokines may be helpful for future treatment of liver fibrosis.

Acute-Phase Proteins↗
PubMedDate not supplied

Auditory event-related cerebral potentials (P300) in hepatic encephalopathy--topographic distribution and correlation with clinical and psychometric assessment.

BACKGROUND/AIMS: Early cognitive disturbances in patients with cirrhosis (Ci) are difficult to assess. Therefore, we evaluated the role of topographic auditory evoked cerebral potentials (P300-EP). METHODOLOGY: Prospective longitudinal study. SETTING: Tertiary clinical care institution. PARTICIPANTS: 45 patients with cirrhosis were compared to 22 healthy subjects. MAIN OUTCOME MEASURES: Hepatic Encephalopathy (HE) was assessed using the clinical grading, standardized psychometric tests, and auditory evoked P300-EP by multichannel EEG recordings. RESULTS: In the patients, the mean P300 peak latency was significantly increased (386.7 +/- 26.7 versus 318.6 +/- 22.2 ms in controls, p < 0.00001). Even in patients with cirrhosis but no HE (n = 18) the P300 peak latency was abnormally prolonged (> 384 ms) in 8 cases (44%). In addition, P180 peak latency was significantly longer in patients with liver cirrhosis as compared to controls (p = 0.021). The maximal P300 amplitude was significantly lowered in patients with liver cirrhosis in the frontocentral and central cortical regions (FZ: p < 0.008; Cz: p < 0.04). Liver function and etiology of liver disease were not related to the increased peak latencies of the P300 and P180 peaks. CONCLUSIONS: P300-EP is a sensitive measure to detect functional cognitive impairment in cirrhotic patients with subclinical HE and clinically apparent HE. Typical changes include latency prolongation and decreased central peak amplitude. Some 40% of patients with no clinical evidence of HE and normal psychometric tests show abnormal results during P300 testing, which is likely to reflect early impairment of cognitive function. Auditory evoked P300 potentials are more sensitive than psychometric testing alone.

Adult↗
PubMedDate not supplied

Modified serum pancreolauryl test in chronic pancreatitis: evaluation in comparison to endoscopic retrograde pancreatography.

BACKGROUND/AIMS: The aim of this study was to assess the applicability and accuracy of the modified serum pancreolauryl test (sPLT) in patients with chronic pancreatitis (cP). METHODOLOGY: We compared the results of a modified serum pancreolauryl test to morphological changes as detected by endoscopic retrograde pancreatography (ERP) in 60 patients with a history suggesting chronic pancreatitis were compared. Serum fluorescein was measured 30, 60, 120, 150, 180 and 240 minutes after the ingestion of fluoresceindilaureat, a standardized breakfast, and i.v. administration of secretin (1 U/kg) and metoclopramide (10 mg). Furthermore, the results of sPLT and ERP were compared to the findings on abdominal ultrasonography. RESULTS: Forty of 60 patients suffered from cP according to ERP criteria. With a fluorescein cut-off point of 4.5 micrograms/ml, sPLT reached a sensitivity of 68% and a specificity of 50%. According to the ROC curve, the optimal cut-off point was at a fluorescein level of 4.1 micrograms/ml; however, predictive accuracy was only slightly improved at this point. In the subgroup of patients with advanced pancreatic duct changes (n = 23), however, sPLT reached a sensitivity of 87% with 16 patients showing a peak fluorescein concentration below 2.5 micrograms/ml. CONCLUSION: Like other indirect pancreatic function tests, modified sPLT provides good recognition of patients with advanced cP but poor identification of patients with mild or moderate cP, leading to an unsatisfying overall performance of the test.

Adult↗