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J Schmidt

Publications and source records attributed to J Schmidt.

At least 181 records · Page 10Linked to original sources
PubMed2000

Hepatitis C virus genotypes in Estonia.

Distribution of hepatitis C virus (HCV) geno(sub)types among 215 Estonian patients hospitalized with acute or chronic hepatitis and with HCV RNA-positive sera was investigated. For genotyping, both multiplex PCR with subtype-specific primers of the core region and RFLP analysis of cDNA of the 5' NCR region were used. These two methods permitted a correct characterization of genotypes, a more truthful characterization of mixed infections, and combined use of single-tube performances. They revealed, respectively, 200 and 202 (93.0% and 93.9%) HCV-positive samples of sera, subtype 1a- 0.9% and 0.9%, 1b- 56.3% and 64.2%, 3a- 13.9% and 22.3%, 2a- 6.5% and 5.6%, type 4 0.5% and 0%, mixed infections- 13.5% and 0%, and unidentified- 1.4% and 0.9%. In the majority of cases (84.7%) both methods gave completely or partially concordant results; in mixed infections, as determined by subtype-specific PCR, only one subtype was revealed by the RFLP method. In the remaining 15.3% of the cases (Ohno- 7.0%, RFLP- 8.3%) only one of the methods was positive. The epidemiological analysis of the dynamics of the subtypes' relative participation may indicate increasing 3a and decreasing 1b subtype infection during recent years.

Acute Disease↗
PubMed2000

Indole alkaloid biosynthesis in Catharanthus roseus: new enzyme activities and identification of cytochrome P450 CYP72A1 as secologanin synthase.

The molecular characterization of CYP72A1 from Catharanthus roseus (Madagascar periwinkle) was described nearly a decade ago, but the enzyme function remained unknown. We now show by in situ hybridization and immunohistochemistry that the expression in immature leaves is epidermis-specific. It thus follows the pattern previously established for early enzymes in the pathway to indole alkaloids, suggesting that CYP72A1 may be involved in their biosynthesis. The early reactions in that pathway, i.e. from geraniol to strictosidine, contain several candidates for P450 activities. We investigated in this work two reactions, the conversion of 7-deoxyloganin to loganin (deoxyloganin 7-hydroxylase, DL7H) and the oxidative ring cleavage converting loganin into secologanin (secologanin synthase, SLS). The action of DL7H has not been demonstrated in vitro previously, and SLS has only recently been identified as P450 activity in one other plant. We show for the first time that both enzyme activities are present in microsomes from C. roseus cell cultures. We then tested whether CYP72A1 expressed in E. coli as a translational fusion with the C. roseus P450 reductase (P450Red) has one or both of these activities. The results show that CYP72A1 converts loganin into secologanin.

Asteraceae↗
PubMed2000

Transient N-acetylgalactosaminylation of mannosyl phosphate side chain in Paramecium primaurelia glycosylphosphatidylinositols.

The surface antigens of the free-living protozoan Paramecium primaurelia belong to the family of glycosylphosphatidylinositol (GPtdIns)-anchored proteins. Using a cell-free system prepared from P. primaurelia, we have described the structure and biosynthetic pathway for GPtdIns glycolipids. The core glycans of the polar glycolipids are modified by a mannosyl phosphate side chain. The data suggest that the mannosyl phosphate side chain is added onto the core glycan in two steps. The first step involves the phosphorylation of the GPtdIns trimannosyl conserved core glycan via an ATP-dependent kinase, prior to the addition of the mannose linked to the phosphate group. We show that dolichol phosphate mannose is the donor of all mannose residues including the mannose linked to phosphate. Furthermore, we were able to identify in vitro a hydrophilic intermediate containing an additional N-acetylgalactosamine linked to the mannosyl phosphate side chain. The addition of this purified hydrophilic radiolabelled intermediate into the cell-free system leads to a loss of the GalNAc residue and its conversion to the penultimate intermediate having only mannosyl phosphate as a side chain. Together the data indicate that the GalNAc-containing intermediate is a transitional intermediate. We suggest that the GalNAc-containing intermediate is essential for biosynthesis and maturation of GPtdIns precursors. It is hypothesized that this oligosaccharide processing in the course of GPtdIns biosynthesis is required for the translocation of GPtdIns from the cytoplasmic side of the endoplasmic reticulum to the luminal side.

Acetylgalactosamine↗
PubMed2000

[Air endotamponade in 52 vitrectomies due to proliferative diabetic retinopathy--retrospective comparison with 40 vitrectomies without endotamponade].

BACKGROUND: In patients with proliferative diabetic retinopathy rebleeding after pars plana vitrectomy is one of the most common complications. We tried to reduce the rate of that complication by using an air endotamponade. PATIENTS AND METHODS: The following study is a retrospective comparison of 2 patient groups both after pars plana vitrectomy due to proliferative diabetic retinopathy. Group 1 was managed with air as endotamponade (n = 52, mean age 61.2 years), group 2 without any endotamponade (n = 40, mean age 59.4 years). Classification of the proliferative diabetic retinopathy as described by Kroll et al. [5] in both groups: 23 and 29 patients with stage A resp., 24 and 10 patients with stage B resp., 5 and 1 patient with stage C respectively. RESULTS: 77% of group 1 patients had an increase os vision by mean of 4.8 vision steps, in 70% of the group 2 patients vision increased by mean of 7.2 vision steps. Complications in both groups as follows: Rebleeding within 14 days 15% vs. 33%, development of secondary glaucoma in 9.6% and 17.5% resp., revitrectomy within 14 days were necessary in 3.8% resp. 2.5% of the patients, later revitrectomy in 13.5% vs. 42.5% of all patients. SUMMARY: Air endotamponade turned out to be appropriate to reduce the rate of postoperative vitreous rebleeding after pars plana vitrectomy due to proliferative diabetic retinopathy. We found no increase of secondary glaucoma or cataract.

Adult↗
PubMed2000

Transjugular intrahepatic portosystemic shunt. Experiences at a liver transplantation center.

OBJECTIVE: Transjugular intrahepatic portosystemic shunt (TIPS) placement is an established therapy for portal hypertension that leads to variceal bleeding or refractory ascites. We present experiences of the role of TIPS at a liver transplantation center. MATERIAL AND METHODS: One hundred and ten patients were referred to the Radiological Department for TIPS placement. One of the 110 patients had recurrent cirrhosis after liver transplantation with refractory ascites. Function of the TIPS was controlled with Doppler US at 1 day, 1 week, 4 weeks and 4 months after TIPS placement and subsequently every 3 months. Shunt insufficiency was supposed when the blood flow velocity within the stent tract was under 50 cm/s and was an indication for TIPS revision. RESULTS: TIPS was placed in 101 patients. After TIPS placement, 10 patients underwent liver transplantation. While waiting for the new liver, none of them developed variceal rebleeding, ascites or other complications of portal hypertension. Two of the 101 patients had episodes of rebleeding. The frequency of patients undergoing TIPS revision within the first year after TIPS placement was 67.5%, within the second year 38.0% and within the third year 24.4%. The revisions led to sufficient reduction of the portosystemic pressure gradient. CONCLUSION: In some liver transplant candidates, TIPS can be useful in minimizing the risk of complications of portal hypertension during the waiting time for a liver transplantation. TIPS can be monitored by Doppler US and revised if occlusion occurs.

Adult↗
PubMed2000

Vascular structure and microcirculation of experimental pancreatic carcinoma in rats.

OBJECTIVE: To study angiogenesis and microcirculation in experimental pancreatic carcinoma. DESIGN: Open experimental study. SETTING: 2 University hospitals, Germany and USA. ANIMALS: 16 male Lewis rats. INTERVENTIONS: Induction of a duct-like pancreatic cancer in the pancreas and peritoneum by interposition of fragments of tumour between 2 inert transparent polymethylmethacrylate plates. MAIN OUTCOME MEASURES: Microcirculation in the tumour and interaction between leucocytes, tumour, and endothelium investigated by intravital microscopy. RESULTS: The density of vessels in the carcinoma was significantly less than in normal pancreatic tissue (p = 0.0004). The vasculature of the tumour was characterised by a lack of differentiation in architecture of vessels, formation of sinusoidal and lacunar vessels and sudden changes in diameter of vessels. Red blood cell velocity differed among tumour vessels, but mean values were similar to those of normal exocrine pancreas. The mixed lymphocyte culture test indicated that the cell line DSL6A was immunogenic. However, high-affinity leucocyte-endothelium-interaction was significantly reduced in the tumour's microcirculation after both orthotopic and heterotopic implantation (p = 0.002). Rates of apoptosis were suppressed in heterotopic tumours compared with orthotopic ones. Tumour growth was faster in heterotopic tumours. CONCLUSIONS: Experimental duct-like pancreatic carcinoma can be differentiated from normal pancreas by: chaotic arrangement of vessels with loss of differentiation of architecture and heterogeneous distribution; the formation of sinusoidal or lacunar vessels; lower vascular density with similar erythrocyte velocity; increase in mean diameter of vessels; reduced leucocyte-endothelium interaction despite confirmed immunogeneity independent of wall shear rates. The site of implantation influences apoptosis and growth rates.

Animals↗
PubMed2000

Comparison of succinylcholine with two doses of rocuronium using a new method of monitoring neuromuscular block at the laryngeal muscles by surface laryngeal electromyography.

We compared the onset of neuromuscular block with succinylcholine (1 mg kg-1) and two doses of rocuronium (0.6 and 0.9 mg kg-1) at the adductor pollicis muscle using electromyography (EMG) and acceleromyography (AMG), and at the adductor laryngeal muscles with a new electromyographic method using a disposable surface electrode attached to the cuff of a tracheal tube. At the larynx, the mean (+/- SD) time to 90% block and the onset time of succinylcholine (38 +/- 15 and 47 +/- 19 s, respectively) were significantly shorter (P < 0.01) than for rocuronium 0.6 mg kg-1 (92 +/- 42 and 106 +/- 38 s) and rocuronium 0.9 mg kg-1 (52 +/- 31 and 64 +/- 30 s). We found that, with comparable degrees of neuromuscular block, the onset time of succinylcholine at the adductor pollicis was significantly shorter (P < 0.01) than for rocuronium 0.6 mg kg-1 and 0.9 mg kg-1 (EMG, 80 +/- 39 vs 145 +/- 48 s and 99 +/- 31 s; AMG, 90 +/- 39 vs 124 +/- 53 s and 106 +/- 38 s). Clinical duration at the adductor pollicis (AMG) was significantly longer (P < 0.01) for both rocuronium groups than for succinylcholine (T4:T1 = 0.7, 54 +/- 18 and 77 +/- 21 vs 8 +/- 6 min). The surface laryngeal electrode proved non-invasive, easy to use and reliable in measuring onset of the neuromuscular block at the larynx.

Adult↗
PubMed2000

Simultaneous determination of neuromuscular block at the larynx, diaphragm, adductor pollicis, orbicularis oculi and corrugator supercilii muscles.

We simultaneously determined the neuromuscular blocking effect of mivacurium 0.2 mg kg(-1) at five muscles in 20 women undergoing gynaecological surgery. Evoked electromyographic responses were obtained using surface electromyography (EMG) at the adducting laryngeal muscles, the diaphragm (lateral to vertebrae T12/L1 or L1/L2) and the adductor pollicis muscle and acceleromyographic (AMG) responses were measured at the orbicularis oculi and the corrugator supercilii muscle. Onset time and times for the first twitch response (T1/T0) to return to 25, 75 and 90% at the adducting laryngeal muscles and the diaphragm were significantly (P<0.005) shorter than at the adductor pollicis, the corrugator supercilii or the orbicularis oculi muscles (mean (SD) onset time: 89 (26) s and 78 (17) s to 202 (45) s, 152 (41) s, 194 (40) s; T1/T0=25%: 10.4 (1.5) and 11.4 (1.2) min versus 20.5 (3.9), 15.9 (3.3), 16.3 (3.7) min; T1/T0=90%: 15.5 (1.6) and 16.1 (1.6) min versus 27.4 (4.6), 21.5 (3.8), 23.3 (5.1) min). Onsetand clinical duration of neuromuscular block at the larynx and the diaphragm after mivacurium 0.2 mg kg(-1) are shorter than in the peripheral muscles. Monitoring of neuromuscular block in the diaphragm was successfully used in all patients.

Adolescent↗
PubMed2000

T-cell apoptosis in situ in experimental autoimmune encephalomyelitis following methylprednisolone pulse therapy.

The apoptosis-inducing effects of i.v. methylprednisolone were investigated as a possible method of controlling inflammation in the CNS in adoptive transfer-experimental autoimmune encephalomyelitis (AT-EAE) in Lewis rats. Two pulses of methylprednisolone were given at the peak of mild and of severe disease. T-cell apoptosis was assessed on spinal cord cross-sections by morphology and TUNEL staining. Concentrations of methylprednisolone were measured in serum, CSF and spinal cord tissue by high-pressure liquid chromatography (HPLC). In severe EAE, 10 mg/kg methylprednisolone increased T-cell apoptosis significantly and T-cell infiltration was marginally decreased. A maximal dose of 50 mg/kg methylprednisolone was superior in both respects and, in contrast to 10 mg/kg methylprednisolone, was also effective in mild EAE. A dose of 1 mg/kg methylprednisolone did not produce notable changes compared with controls treated with phosphate-buffered saline. Serum, CSF and spinal cord concentrations of methylprednisolone measured by HPLC 2 h after a single i.v. injection of 10 or 50 mg/kg methylprednisolone revealed significantly higher methylprednisolone concentrations in severe EAE compared with mild disease. With 50 mg/kg methylprednisolone, we obtained serum and CSF concentrations in the region of 10(-5) M methylprednisolone. We also studied the expression of bcl-2, a typical anti-apoptotic regulatory protein, in T cells, and found no change after methylprednisolone treatment compared with controls. Methylprednisolone did not induce apoptosis of oligodendrocytes, which would have been an unwanted side effect in CNS cells. This study provides evidence that methylprednisolone dose-dependently augments T-cell apoptosisin situ in AT-EAE. Our results may have implications for the use of glucocorticosteroids at very high doses in the treatment of inflammatory disorders of the CNS, such as multiple sclerosis, or of other target organs.

Animals↗
PubMed2000

Cigarette smoke enhances ethanol-induced pancreatic injury.

Alcohol induces pancreatic ischemia, but the mechanisms promoting pancreatic inflammation are unclear. We investigated whether cigarette smoke inhalation is a cofactor in the development of ethanol-induced pancreatic injury. Cigarette smoke was administered to anesthetized rats alone or in combination with intravenous ethanol infusion. Control animals received either saline or ethanol alone. Pancreatic capillary blood flow and leukocyte-endothelium interaction in postcapillary venules were evaluated by intravital microscopy. Leukocyte sequestration was assessed by measurement of myeloperoxidase activity in pancreatic tissue, and pancreatic injury evaluated by histology. Ethanol decreased pancreatic blood flow progressively over 90 minutes (p < 0.001 vs. baseline), but neither leukocyte-endothelium interaction nor leukocyte sequestration was altered. Cigarette smoke alone reduced pancreatic blood flow temporarily (p < 0.01 vs. baseline) and increased leukocyte-endothelium interaction (roller p < 0.001, sticker p < 0.01 vs. baseline). Cigarette smoke potentiated the impairment of pancreatic capillary perfusion caused by ethanol, and both the number of rolling leukocytes and myeloperoxidase activity levels were increased compared to ethanol or nicotine administration alone (p < or = 0.05 and p < or = 0.01, respectively). This study demonstrates that ethanol induces pancreatic ischemia and that cigarette smoke leads to both temporary pancreatic ischemia and minimal leukocyte sequestration. Cigarette smoke potentiates the amount of pancreatic injury generated by ethanol alone. Smoking therefore seems to be a contributing factor in the development of alcohol-induced pancreatitis in the rat model.

Animals↗
PubMed2000

Influence of gastrointestinal hormones on tumor microcirculation of experimental pancreatic cancer in the rat.

BACKGROUND/AIMS: Gastrointestinal hormones influence the microcirculation in the normal pancreas. In the present study, we studied the effect of cerulein and somatostatin on pancreatic cancer microcirculation after orthotopic and nonorthotopic tumor implantation. METHODS: In 36 male Lewis rats (150-180 g) induction of a ductlike pancreatic cancer was achieved by intrapancreatic or intraperitoneal tumor fragment interposition between two inert transparent polymethyl methacrylate plates. After 4 weeks, intravital microscopy of the tumor microcirculation was performed in a temperature-controlled immersion chamber. The animals received 5 microg/kg cerulein or 3 mg/kg somatostatin for 1 h intravenously. The erythrocyte velocity in normal pancreatic capillaries or in tumor vessels was measured. RESULTS: The erythrocyte velocity in the capillaries of the normal pancreas was 1.01 +/- 0.11 mm/s at baseline and increased to 1.64 +/- 0.09 mm/s after cerulein stimulation (p = 0.007). Pancreatic cancer vessels demonstrated no increase in erythrocyte velocity after orthotopic (baseline 0.95 +/- 0.14 mm/s, after 1 h 0.86 +/- 0.13 mm/s; n.s.) and nonorthotopic tumor implantation (baseline 0.91 +/- 0.12 mm/s, after 1 h 0.95 +/- 0.14 mm/s; n.s.) after cerulein stimulation. Somatostatin decreased the erythrocyte velocity both in normal pancreas (baseline 0.87 +/- 0.02 mm/s, after 1 h 0.60 +/- 0.07 mm/s; p = 0.01) and in pancreatic cancer (baseline 0.85 +/- 0.20 mm/s, after 1 h 0.63 +/- 0.18 mm/s; p = 0.02) after orthotopic tumor implantation. There was no effect of somatostatin after nonorthotopic tumor implantation (baseline 0.90 +/- 0.10 mm/s, after 1 h 0.88 +/- 0.14 mm/s; n.s.). CONCLUSION: These data suggest that pancreatic cancer microcirculation lacks physiological blood flow control by stimulatory hormones, in contrast to the normal pancreas.

Animals↗
PubMed2000

Arterial blood pressure following different types of urinary stone therapy. Presented at the 8th European Symposium on Urolithiasis, Parma, Italy, 1999.

OBJECTIVE: Several studies reported increased blood pressure (BP) values following extracorporeal shock wave lithotripsy (ESWL) treatment of renal stones. It is unclear, however, whether this is due to ESWL, since nephrolithiasis itself increases the relative risk of developing hypertension. Therefore we prospectively studied the BPs of stone patients undergoing different types of treatment. METHODS: 252 stone patients (63% males, 37% females, median age 44.3, range 11.7-86.4 years) participated. 168 suffered from uretral stones: 50 underwent ESWL; 40 ureteroscopy, and 78 patients passed stones spontaneously (SP). 84 had renal stones: 60 underwent ESWL; 8 percutaneous nephrolithotomy/open surgery, and 16 no treatment. Systolic (SBP) and diastolic (DBP) BP were measured according to Riva-Rocci prior to, immediately after, and 3, 6, 12, 18 and 24 months after stone therapy. RESULTS: Immediately after SP, SBP decreases, whereas after active stone treatment increases (highest after ESWL) in SBP were seen. DBP was unchanged. During the further follow-up, a gradual increase in BP was observed in all groups. At 24 months in all groups, regardless of the stone location and type of treatment, SBP and DBP were significantly higher than the pretreatment levels (p = 0.000). There was no a difference between renal and ureteral stones, or between the ESWL treatment and the other groups. CONCLUSION: Renal stone disease itself rather than the type of treatment significantly increases SBP and DBP during a follow-up period of 24 months. The underlying mechanisms remain to be elucidated.

Adult↗
PubMed2000

Pigment epithelium defects after submacular surgery for choroidal neovascularization: first results.

It was the aim of this study to compare postoperative pigment epithelium defects after submacular surgery for well-defined choroidal neovascularization (CNV) with preoperative fluorescein angiogram (FAG), indocyanine green angiogram (ICG), and intraoperative findings of the excised neovacularization. Surgical removal of the CNV was videotaped. By means of a gauge the absolute size of an anatomic structure was determined which was visible on video, FAG, and ICG as well. Postoperatively another FAG was performed to further examine the funduscopically visible pigment epithelium defect. By comparison with the above-mentioned anatomic structure it was thus possible to determine the exact size of CNV and pigment epithelium defect. The extent of the pigment epithelium defect as determined on postoperative FAG after submacular surgery surpasses the size of CNV as measured in FAG, ICG, and anatomical preparation.

Adult↗
PubMed2000

Epidemiology and clinicopathology of aortic dissection.

STUDY OBJECTIVES: To determine the incidence and mortality as well as to analyze the clinical and pathologic changes of aortic dissection. DESIGN AND SETTING: A population-based longitudinal study over 27 years on a study population of 106,500, including 66 hospitalized and 18 nonhospitalized consecutively observed patients. MEASURES: Analysis of data from the medical, surgical, and autopsy records of patients with aortic dissection. RESULTS: Altogether, 86 cases of aortic dissection were found in 84 patients, corresponding to a 2.9/100,000/yr incidence. Sixty-six of the 84 patients (79%) were admitted to the hospital, and 18 patients (21%) died before admission. Their ages ranged from 36 to 97 years, with a mean of 65. 7 years. The male/female ratio was 1.55 to 1. A total of 22.7% of the hospitalized patients died within the first 6 h, 33.3% within 12 h, 50% within 24 h, and 68.2% within the first 2 days after admission. Six patients were operated on, with a perioperative mortality of two of six patients and a 5-year survival of two of six patients. All patients who were not operated on died. Pain was the most frequent initial symptom. Every patient had some kind of cardiovascular and respiratory sign. Neurologic symptoms occurred in 28 of 66 patients (42%). Five patients presented with clinical pictures of acute abdomen and two with acute renal failure. Trunk arteries were affected in 33 of the 80 autopsied cases (41%), and rupture of aorta was seen in 69 cases (86%). In five cases, spontaneous healing of dissection was also found. The ratio of proximal/distal dissections was 5.1 to 1. All 18 prehospital cases were acute. Fifty-nine cases (89.4%) were acute at admission, and 7 cases (10.6%) were chronic dissections. Hypertension and advanced age were the major predisposing factors. CONCLUSION: Aortic dissection was the initial clinical impression in only 13 of the 84 patients (15%). Thus, 85% of the patients did not receive immediate appropriate medical treatment. For this reason, these late-recognized and/or unrecognized cases may be regarded as an untreated or symptomatically treated group, whose course may resemble the natural course of aortic dissection.

Adult↗
PubMed2000

Clinical experiences with a new semi-quantitative solid phase immunoassay for rapid measurement of procalcitonin.

A self-developing solid-phase immunoassay (B.R.A.H.M.S. PCT-Q, B.R.A.H.M.S.-Diagnostica GmbH, Hennigsdorf, Germany) has recently become available for the semi-quantitative and rapid measurement of procalcitonin (PCT). In this study we examined the validity of this assay at daily clinical routine conditions at five different hospitals in a prospective study. After development of the assay (200 microl plasma, 30 minutes incubation), PCT levels were categorized into four groups (< 0.5 microg/l; > or = 0.5-< 2 microg/l; > or = 2-< 10 microg/l; > or = 10 microg/l) according to the provided reference scale. Samples from patients with suspected elevation of PCT of different etiology (n=237) were read by various analyzers and compared with the results of the Lumitest PCT (B.R.A.H.M.S.-Diagnostica GmbH, Hennigsdorf, Germany). A total of 74.7% of measurements were categorized according to the results of the LumitestPCT, 24.5% were read within the next lower or higher category. Using a +/- 10% range at the reference concentrations (20% at 0.5 microg/l), 82.7% of samples were correctly categorized and 16.4% within the next categories. Using a cut-off value of 2.0 microg/l, 92.0% (94.1% for +/- 10%) of the results were correctly categorized. The semi-quantitative solid phase immunoassay allows a rapid, simple and semi-quantitative measurement of plasma PCT. The validity of the test results and its ease of use are sufficient to support acute diagnostic decisions. However, for the follow-up of PCT concentrations and routine daily measurements, the quantitative luminometric assay should be preferred, when available.

Calcitonin↗
PubMed2000

Regulation of Fas and FasL expression on rat Schwann cells.

Although the PNS belongs to the immune privileged sites, it can become a target of immune attacks by invading T cells, causing inflammation and destruction. Yet the PNS also has a protective potential by eliminating the inflammatory cells via apoptosis. In analogy with other immune-protected sites, participation of the apoptosis-inducing Fas/FasL molecules could play an important role. To assess the possible involvement of the Fas/FasL system in T-cell apoptosis in the PNS of the rat, we characterized Fas and FasL expression on neonatal rat Schwann cells (SC) in vitro. Cells were stimulated in vitro with interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), or a combination of both. We observed upregulation of FasL expression under the influence of IFN-gamma, while adding TNF-alpha alone to the culture medium had no effect. IFN-gamma and TNF-alpha acted synergistically, leading to an increased FasL expression that reached its maximum 70 h after cytokine exposure, as shown by FACS analysis, SDS-PAGE, and Western blot. Fas expression on untreated SC showed fluctuating levels, while addition of IFN-gamma and TNF-alpha suppressed Fas expression completely. These findings are in accord with recently published results showing Fas and FasL expression on malignant human cells, derived from brain tumors and upregulation of FasL on astrocytes after exposure to IFN-gamma and TNF-alpha. Furthermore, FasL-expressing SC could be revealed by immunostaining of sciatic nerve from Lewis rats suffering from experimental autoimmune neuritis (EAN). We suggest that Fas/FasL expression on SC may contribute to the elimination of invading autoreactive T cells in the PNS in concert with other immune defense mechanisms.

Animals↗