Biomedical subjects

E H Farthmann

Publications and source records attributed to E H Farthmann.

165 records · Page 10Linked to original sources

PubMedDate not supplied

Aminoterminal propeptide of type III procollagen: a marker of hepatic fibrosis after bile duct obstruction in the monkey.

BACKGROUND/AIMS: In an experimental study in monkeys, liver fibrosis development after segmental bile duct obstruction was investigated and correlated with the aminoterminal propeptide of type III procollagen (PIIINP). MATERIALS AND METHODS: Segmental bile duct obstruction was produced by ligation and section of the left hepatic bile duct in all monkeys. Fibrosis induction was examined by intravenous leukotriene C4 (LTC4, 5 nmol/kg) application, endogenous LT-production stimulated by endotoxin (LPS,salmonella abortus equi, 50 ng/kg), fibrosis inhibition by dexamethasone (1 mg/kg) intramuscularly and subsequent endogenous LT-production stimulation by LPS (50 ng/kg). Ligated and unligated liver lobe biopsies were taken 3, 7 and 12 weeks after ligation. All portal areas were measured morphometrically. PIIINP was measured by a specific radioimmunoassay each week and correlated with the morphometric results. RESULTS: Bile duct obstruction leads to secondary sclerosing cholangitis with bile duct vanishing and subsequent biliary cirrhosis combined with perivenous sclerosis and cavernous transformation of the terminal vein. The collagen concentration increased in the nonligated lobe from mean +/-SEM 1.05 +/- 0.03% to 1.53 +/- 0.19% only after LTC4 and with no difference in the other groups. In the ligated lobe collagen concentration increased significantly in all groups continuously from 1.05 +/- 0.03% up to: controls 6.1 +/- 0.9%, dexamethasone 5.9 +/- 0.8%, LPS 8.2 +/- 0.8%, LTC4 9.075 +/- 1.4%. PIIINP concentration rose within 6 weeks in the controls with hepatic bile duct obstruction from 34.43 +/- 15 ng/ml up to 57 +/- 13.27 ng/ml, after dexamethasone to 48.5 +/- 18.23 ng/ml, after LPS to 57 +/- 13.27 ng/ml, after LTC4 to 80.25 +/- 16.04 ng/ml. After 12 weeks, PIIINP decreased in the controls resp. after dexamethasone to 41.25 +/- 6.94 ng/ml resp. 33.5 +/- 7.72 ng/ml and increased after LPS resp. LTC4 up to 64.25 +/- 17.07 ng/ml resp.104 +/- 22.46 ng/ ml. The correlation of collagen deposition and PIIINP was in the controls r = 0.83, after dexamethasone r = 0.71, after LPS r = 0.83 after LTC4 r = 0.91. CONCLUSION: PIIINP determination after segmental bile duct obstruction correlates with collagen deposition and allows evaluation of hepatic fibrosis activity.

Animals↗

PubMedDate not supplied

Early detection of graft dysfunction after orthotopic liver transplantation in man by serum and biliary bile acid analysis.

BACKGROUND/AIMS: Several routine parameters are used to monitor the functional state of the liver after orthotopic liver transplantation (OLT). These parameters may not fully mirror hepatic function and even liver biopsy may be unreliable during onset of graft rejection. Additional analytical methods on bile constituents for recognition of early graft dysfunction have been assessed. Conflicting results have prompted discussions about the usefulness of monitoring serum bile acids and biliary lipids after OLT with respect to early recognition of graft dysfunction. MATERIALS AND METHODS: Routine serum liver function tests were compared with serum bile acid (BA) concentrations and output of biliary lipids (BA, phospholipids, cholesterol) over 20-25 days in 12 patients after (OLT) with different postoperative courses. RESULTS: 4 patients had an uneventful postoperative course (group 1); 5 experienced a rejection episode (group 2); 3 demonstrated a poor initial graft function (group 3). In group 1 aspartate-aminotransferase (AST) (<20 U/L), urinary BA excretion (<21 mmoles/day) and normalized bile flow (NBF; 72 +/- 25 ml bile/mmole BA) fell into the normal range within 4 days after OLT; serum BA concentration (<20 mM) was within normal on the first postoperative day. Output of biliary BA, phospholipids, cholesterol and bile production increased continuously during the observation period reaching values of 11.2 +/- 3.3 mmoles/day, 2.7 +/- 0.9 mmoles/day, 1.3 +/- 0.5 mmoles/day and 761 +/- 221 ml/day, respectively. The ratio of taurocholate/glycocholate (TC/GC) decreased from an initial value of 0.45 to 0.11. Group 2 yielded similar values until rejection appeared. At this time serum BA concentration, NBF urinary BA excretion and TC/GC-ratio rose; biliary lipid output and bile flow decreased. In most of the patients these changes occurred at the same day or 1-3 days earlier than that of AST. CONCLUSIONS: The determination of serum BA concentration, TC/GC-ratio, output of biliary lipids and NBF may indicate graft dysfunction 1-3 days earlier than AST and, thus, may provide useful parameters for early recognition of liver graft dysfunction.

Adult↗

PubMedDate not supplied

Phenotypical and functional differences of tumor-infiltrating lymphocytes from human colorectal cancers induced by costimulation with rIL-2 and rIL-4 in vitro.

The influence of recombinant human interleukin-4 (rIL-4) on the proliferation and cytotoxic activity of tumor-infiltrating lymphocytes (TIL) from human colorectal cancers was investigated TIL and peripheral blood lymphocytes (PBL) were cultured for 3-5 weeks. Under simultaneous stimulation with rIL-2 and rIL-4 the proliferation of TIL was less pronounced compared to stimulation with rIL-2 alone. In rIL-2 expanded TIL an outgrowth of CD56+ cells was observed. Concordantly, the expression of CD3+ cells was low. The number of CD56+ cells could be reduced significantly in TIL and PBL by stimulation with rIL-2 and rIL-4 simultaneously while the number of CD3+ cells increased. In TIL and PBL co-stimulation with rIL2 and rIL-4 resulted in higher CD4/CD8 ratios as compared to expansion with rIL-2 alone. In a 72 hour cytotoxicity assay the rIL-2/rIL-4 expanded TIL and PBL showed a lower lytic activity against autologous tumor targets in comparison to the rIL-2 expanded lymphocytes. In contrast, the cytotoxic activity of rIL-2/rIL-4 cultured TIL against allogeneic tumor cells was higher than in rIL-2 stimulated TIL.

Adult↗