Analysis of risk factors for the development of late hepatic artery thrombosis: do CREG mismatches play a role?
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Cross Reactions↗
Biomedical subjects
U Neumann
Publications and source records attributed to U Neumann.
2-(diethylamino)thieno1,3ŏxazin-4-ones as stable inhibitors of human leukocyte elastase.
A series of 2-(diethylamino)thieno1,3ŏxazin-4-ones was synthesized and evaluated in vitro for inhibitory activity toward human leukocyte elastase (HLE). The Gewald thiophene synthesis was utilized to obtain several ethyl 2-aminothiophene-3-carboxylates. These precursors were subjected to a five-step route to obtain thieno2,3-d1,3ŏxazin-4-ones bearing various substituents at positions 5 and 6. Both thieno2,3-d and thieno3,2-d fused oxazin-4-ones possess extraordinary chemical stability, which was expressed as rate constants of the alkaline hydrolysis. The kinetic parameters of the HLE inhibition were determined. The most potent compound, 2-(diethylamino)-4H-1benzothieno2,3-d1,3ŏxazin-4-one, exhibited a K(i) value of 5.8 nM. 2-(Diethylamino)thieno1, 3ŏxazin-4-ones act as acyl-enzyme inhibitors of HLE, similar to the inhibition of serine proteases by 4H-3,1-benzoxazin-4-ones. The isosteric benzene-thiophene replacement accounts for an enhanced stability of the acyl-enzyme intermediates.
Enzyme Inhibitors↗
[The effect of erythropoietin (rh-EPO) om in vitro proliferation of granulocyte/monocyte-determined stem cells in bone marrow and peripheral blood].
AIM: The aim of the investigation was to determine the effect of recombinant human erythropoietin (rh-EPO) therapy on in-vitro proliferation of granulocyte/monocyte(gm)-determined stem cells in bone marrow and peripheral blood. PATIENTS AND METHODS: The study comprised 28 dialysis patients (15 female, 13 male, aged between 22 and 78 years, dialysis sessions 3 times weekly 4 to 5 hours, mean duration time of dialysis treatment 4 to 99 months). Stem cell parameters were estimated before and after reaching the target hematocrit and the absolute number of leukocytes in peripheral blood was measured. RESULTS: No alteration in total leukocyte number (PMN, monocytes, lymphocytes) of peripheral blood was found. Dialysis patients had a diminished proliferation capacity of colony forming unit-granulocyte/monocyte (CFU-GM) in bone marrow and an increased one in peripheral blood. The CFU-GM proliferation capacity in bone marrow improved during rh-EPO (34.3 +/- 5.8 x 10(5)/ml vs 120.5 +/- 37.8 x 10(5)/ml), whereas no changes in peripheral blood could be observed (46.7 +/- 7.15 x 10(5)/ml vs 37.6 +/- 12.05 x 10(5)/ml).
Adult↗
[Bilobar liver hematoma and spontaneous rupture after cesarean section].
A 25-year-old woman delivered a healthy baby in the 34th week of gestation by caesarean section due to placental abruption and fetal bradycardia. On the following day she developed dyspnea, tachycardia, hypotension and rising serum transaminase levels. After exclusion of a pulmonary embolism, the abdominal CT scan and cavography revealed a subcapsular hematoma of the entire dorsal liver surface and compression of the retrohepatic vena cava. During laparotomy a spontaneous rupture of the liver capsule with intraperitoneal hemorrhage was found. The dorsal liver was decapsulated and the subcapsular hematoma completely removed. The postoperative course was uneventful.
Abruptio Placentae↗
[Laparoscopic therapy of diaphragmatic rupture on both sides].
The usual treatment for operative repair of diaphragmatic injuries is laparotomy or thoracotomy. We report on a 26-year-old patient, who was treated by laparoscopic surgery for a rupture on both sides of the diaphragm. The operation was without complications and the advantages of minimally invasive laparoscopic surgery were clearly evident. There was much less strain on the patient and the postoperative recovery period was short. In addition, for unclear findings there is a high diagnostic potential in laparoscopy. The rupture on the right side of the diaphragm was not diagnosed until laparoscopy, although our patient underwent extensive diagnostics prior to the intervention.
Adult↗
Popliteal entrapment syndrome: non-invasive diagnosis and complete recovery after surgery in an 11-year-old boy.
We present an unusual case of popliteal entrapment syndrome type I in an 11-year-old boy. Presenting symptoms were exercise-related pain and pallor in his left lower leg. The diagnosis of popliteal entrapment syndrome was established by acral plethysmography, colour-coded Doppler sonography and MRI. After myotomy of the gastrocnemius muscle the symptoms resolved completely. Post-operative duplex scan showed normal blood flow, even in plantar flexion of the foot.
Arterial Occlusive Diseases↗
Microcystin in cyanobacterial blooms in a Chilean lake.
Cyanobacterial blooms dominated by Microcystis sp. occurred in lake Rocuant ("marisma", near Concepción/Chile) in February 1995 and 1996. In the bloom samples collected in both years the hepatotoxin microcystin was detected by RP-HPLC in both samples and in the sample of 1995 also by a toxicity assay using primary rat hepatocytes. In the bloom of 1995, the microcystin content of the dry bloom biomass was determined to be 130 micrograms/g on the basis of the RP-HPLC peak area and 800 micrograms/g on the basis of the rat hepatotoxicity assay, respectively. In the bloom of 1996, RP-HPLC analysis revealed a microcystin content of 8.13 micrograms/g bloom material dry weight. In this year no hepatotoxicity was measured using a concentration range up to 0.8 mg (d. w.) of bloom material per ml in the rat hepatotoxicity assay. This is the first report on the detection of microcystins in Chilean water bodies.
Animals↗
Isolation and structural characterization of glycosphingolipids of in vitro propagated human umbilical vein endothelial cells.
To investigate in detail the expression of glycosphingolipids (GSLs) on endothelial cells, 4.85 x 10(9) human umbilical vein endothelial cells (HUVECs) were cultivated in a 2 l bioreactor using microcarriers as a support for anchorage dependent growing cells. Neutral GSLs and gangliosides were isolated and their structures were determined by TLC immunostaining, fast atom bombardment-mass spectrometry (FAB-MS) of the native GSLs, and gas chromatography-electron impact mass spectrometry (GC-EIMS) of partially methylated alditol acetates. GbOse4Cer, GbOse3Cer, and LacCer, all carrying mainly C24- and C16-fatty acid beside C18-sphingosine, were detected as the major neutral GSLs (36%, 23%, and 15% of the total orcinol stain, respectively); GlcCer, nLcOse4Cer, and nLcOse6Cer were expressed to substantial minor amounts (9%, 12%, and 5% of the total orcinol stain, respectively). TLC immunostaining revealed the presence of lipid bound Lewisx antigen, whereas the isomeric Lewisa structure was detectable only in very low quantities. GM3(Neu5Ac) with C18-sphingosine was the major ganglioside constituting about 90% of the whole ganglioside fraction. The fatty acid composition was determined by GC-MS of fatty acid methyl esters, indicating the predominance of C24- and C16-substituted GM3(Neu5Ac), followed by C18- and C22-substituted species. Terminally alpha2-3 sialylated neolacto-series ganglioside IV3Neu5Ac-nLcOse4Cer was the second most abundant ganglioside in HUVECs (8% of the total resorcinol stain), and IV6Neu5Ac-nLcOse4Cer and VI3Neu5Ac-nLcOse6Cer (together less than 2% of total resorcinol stain) were found in minor quantities. Lipid bound sialyl Lewisx antigen with poly-N-acetyllactosaminyl chains, and traces of gangliotetraose-type gangliosides GM1 and GD1a were identified by TLC immunostaining. The expression of dominant neutral GSLs LacCer, GbOse3Cer, and GbOse4Cer, and of ganglioside GM3(Neu5Ac) was assayed by indirect immunofluorescence microscopy of cell layers grown in chamber slides, each showing different plasma membrane and subcellular distribution patterns. The complete structural characterization of GSLs from HUVECs contributes to our understanding about their functional role, not only of the carbohydrate but also of the lipid moiety, as receptors for bacterial toxins, as cell surface antigens of cellular interaction and as receptors for blood components and macromolecules of the extracellular matrix.
Bioreactors↗
Equine CRISP-3: primary structure and expression in the male genital tract.
Although originally described in the male rodent genital tract, cysteine-rich secretory proteins (CRISPs) are expressed in a variety of mammalian tissue and cell types. The proteins of the male genital tract have been observed associated to spermatozoa and are believed to play a role in mammalian fertilization. Here we describe the identification and primary structure of the first equine member of the CRISP family. Equine CRISP-3 is transcribed and expressed in the stallion salivary gland, in the ampulla and the seminal vesicle. It displays all 16 conserved cysteine residues and shows 82% homology to human and 78% to guinea pig CRISP-2 (AA1, TPX 1) and 77% to human CRISP-3. In contrast to other mammalia, in the horse CRISP-3 is synthesized in great amounts in the accessory sexual glands, ampulla and seminal vesicle, thus allowing the isolation of equine CRISP-3 in amounts suitable for biochemical, physiological and structural studies from stallion seminal plasma.
Amino Acid Sequence↗
[Fatal course of measles infection in a patient with a low-grade malignant non-Hodgkin lymphoma].
HISTORY AND CLINICAL FINDINGS: A 35-year-old man, for 6 years known to have non-Hodgkin lymphoma (NHL) was admitted because of deteriorating general condition, drowsiness and 11 days of flu-like symptoms. A generalized rash had been noted 5 days after onset of symptoms. His 2-year-old son had fallen ill with measles a few days earlier. The patient had reportedly had measles as a child. On admission a generalized rash was found, he had a fever of 40.5 degrees C, tachypnoea, conjunctivitis and possible meningismus. INVESTIGATIONS: Lactate dehydrogenase activity was raised to 458 U/ml, and C-reactive protein to 240 mg/ml. Cerebrospinal fluid contained 8/3 cells and protein of 269 mg/l. The chest radiogram revealed opacification in the left upper lobe. Computed tomography of the skull demonstrated a pansinusitis. DIAGNOSIS, TREATMENT AND COURSE: As measles encephalitis seemed unlikely he was treated for the measles superinfection of bacterial pneumonitis (measles RNA in the bronchoalveolar lavage) and the sinusitis with broad-spectrum antibiotics. After initial improvement artificial ventilation had to be be gun on day 3 because of an acute respiratory distress syndrome, diagnosed both clinically and radiologically. Despite additional antiviral and intensive medical treatment he died on day 11. CONCLUSION: Patients with impaired immunocompetence due to NHL may lose their immunological "memory" for a previous measles infection. Prevention of exposure may therefore be necessary, in addition to early hyperimmunoglobulin administration.
Adult↗
A single amino acid substitution changes ribonuclease 4 from a uridine-specific to a cytidine-specific enzyme.
The structural features underlying the strong uridine specificity of ribonuclease 4 (RNase 4) are largely unknown. It has been hypothesized that the negatively charged alpha-carboxylate is close to the pyrimidine binding pocket, due to a unique C-terminal deletion. This would suppress the cleavage of cytidine-containing substrates [Zhou, H.-M., and Strydom, D. J. (1993) Eur. J. Biochem. 217, 401-410]. Replacement of the alpha-carboxylate by an alpha-carboxamide in a fragment complementation system decreased both (kcat/Km)CpA and (kcat/Km)UpA , thus refuting the hypothesis. However, model building showed that the deletion allowed the side chain of Arg-101 to reach the pyrimidine binding pocket. From the 386-fold reduction in (kcat/Km)UpA in RNase 4;R101N, it is concluded that this residue functions in uridine binding, analogous to Ser-123 in RNase A. In addition, it may have an effect on Asp-80. The 2-fold increase in (kcat/Km)CpA in the mutant R101N and the close proximity of the side chains of Arg-101 and Asp-80 suggested that the latter could be involved in suppressing CpA catalysis. The substrate specificity of RNase 4;D80A was completely reversed: (kcat/Km)UpA decreased 159-fold, whereas (kcat/Km)CpA increased 233-fold. The effect on CpA was unexpected, because the corresponding residue in bovine pancreatic RNase A (Asp-83) hardly affects cytidine-containing substrates. Furthermore, the residue is conserved in nearly all sequences of mammalian RNase 1. Thus, an evolutionary highly conserved residue does not necessarily function in the same way in homologous enzymes. A model, which proposes that the structure of RNase 4 has been optimized to permanently fix the position of Asp-80 and impede its movement away from the pyrimidine binding pocket, is presented.
Amino Acid Sequence↗
Novel thieno[2,3-d][1,3]oxazin-4-ones as inhibitors of human leukocyte elastase.
A series of thieno[2,3-d][1,3]oxazin-4-ones was synthesized and evaluated in vitro for inhibitory activity toward human leukocyte elastase. New synthetic routes to 2-alkoxy-, 2-alkylthio-, and 2-sec-amino-substituted derivatives are reported. This study demonstrates the versatility of 2-aminothiophenes prepared by Gewald reaction as a synthetic entry to serine protease-inhibiting, fused 1,3-oxazin-4-ones. Introduction of ethoxy, n-propoxy, and ethylthio groups at C-2 delivered the most potent inhibitors of this series with Ki values lower than 11 nM. Kinetic studies and product analyses revealed the formation of acyl-enzymes as a result of the attack of the active site serine at the carbon C-4 and subsequent deacylation. This mode of action is similar to the inhibition of serine proteases by 4H-3,1-benzoxazin-4-ones. Replacement of the benzene ring in benzoxazinones by a (substituted) thiophene led to improved hydrolytic stability and retained inhibitory potency.
Enzyme Inhibitors↗
[Treatment of advanced Budd-Chiari syndrome by liver transplantation].
Budd-Chiari syndrome (BCS) with hepatic vein occlusion is a rare disorder that can effectively be treated in advanced stages with orthotopic liver transplantation. We report on 16 patients who received 18 liver grafts and were followed up for at least 2 years. In 7 patients a hematological disorder was confirmed by bone marrow biopsy. One patient died after 4 months due to cytomegalovirus pneumonia; another patient died after 2 years due to progressive liver failure after portal vein thrombosis. The actuarial 5-year survival rate is 87.5% compared to 85.3% in all other 710 orthotopic liver transplantations performed from September 1988 to December 1995 at our institution. Anticoagulation consisted of intravenous heparin and overlapping continuation with dicoumarin. Three patients received hydroxyurea for thrombocytosis, one patient for 1 week only early after the transplantation. Two postoperative abdominal hemorrhages required laparotomy. Two patients had to be retransplanted, one for thrombosis of the hepatic artery and portal vein after discontinuation of dicoumarin due to GI bleeding and one for hepatic vein thrombosis after insufficient dicoumarin intake. Terminal BCS represents a good indication for orthotopic liver transplantation; however, life-long, closely monitored anticoagulation is essential.
Adolescent↗
Combined liver-kidney transplantation: long-term follow up in 18 patients.
Since August 1992, 18 patients underwent combined liver and kidney transplantation. Eight patients had lymphocytotoxic antibodies pretransplant and 5 of these patients (27.7%) had a positive crossmatch. Fifteen patients received cyclosporine-based immunosuppression and 3 patients were treated with a tacrolimus-based immunosuppressive protocol. One patient died in the postoperative course due to intractable bleeding episodes after 96 days and one kidney graft was lost due to technical complications. The 1 year survival rate of patients with combined transplantation was 95% vs 87% in patients with liver transplantation alone. None of the patients with a positive crossmatch experienced a hyperacute rejection of the kidney. The long-term patient and graft survival was not impaired in patients with a positive crossmatch. These results suggest that combined liver-kidney transplantation is a safe treatment for end-stage liver and renal disease. A positive crossmatch or positive lymphocytotoxic antibodies are not contraindications for a combined transplantation.
Adult↗
The impact of donor organ quality on postoperative liver function after orthotopic rat liver transplantation.
The impact of donor factors for posttransplant liver function was evaluated in the model of orthotopic rearterialized liver transplantation in the rat. The effect of donor fasting, parenteral hyperalimentation, hypotension, warm ischemia and endotoxins on histology, clinical chemistry and MEGX test was analyzed in syngeneic and allogeneic recipients of livers stored for 4 hrs on ice. In syngeneic animals, 20 min of warm ischemia led to significantly elevated serum transaminase levels and degree 2 histological damage on POD 2. Endotoxins produced a grade 1 histological damage. All groups had a lower MEGX formation rate compared to controls. In allogeneic animals, warm ischemia was the single most detrimental parameter. The strength of the rejection response on POD 8 did not depend on the type of donor pretreatment. The major finding of this non-survival study is the deleterious effect of warm ischemia and endotoxin on the functional and structural integrity of liver grafts after 4 hrs of cold ischemia.
Animals↗
Glycosphingolipids of skeletal muscle: I. Subcellular distribution of neutral glycosphingolipids and gangliosides in rabbit skeletal muscle.
Membrane vesicles were prepared from rabbit skeletal muscle, separated by sucrose density gradient centrifugation and characterized by their specific marker enzymes, ligand binding, and ion flux activities. The fractions obtained (in the order of increasing density) were sarcolemma (SL), T-tubules (TT), sarcoplasmic reticulum (SR1 and SR2) and triads/mitochondria (Tr/M). Their glycosphingolipid compositions were analyzed by biochemical and immunochemical methods with specific antibodies (TLC immunostaining) and characteristic patterns were obtained from respective membrane fractions, expressed on a protein basis. Glucosylceramide, the main neutral glycosphingolipid of rabbit muscle, was found in SL and TT fractions, whereas SR and Tr/M vesicles lack this compound. Lactosylceramide was selectively recovered in the SR1 fraction. GM3(Neu5Ac), the main ganglioside in rabbit muscle, was found to account for 64% in the SL, 13% in the TT, 7% in the SR1, 3% in the SR2 and 13% in the Tr/M fractions. IV3Neu5Ac-nLcOse4Cer was mostly abundant in SL and decreased in the order SL > TT, Tr/M > SR1, SR2. IV6Neu5Ac-nLcOse4Cer was only detected in the SL and Tr/M fractions in noteworthy quantities. Ganglioseries gangliosides GM1, GD1a, GD1b and GT1b displayed homogeneous distribution patterns in each membrane preparation. They were expressed only in small amounts but mainly in SL, TT and Tr/M vesicles and to less extent in SR1 and SR2 fractions. The presence of GM3(Neu5Ac) in the SL as well as on subcellular level was confirmed in transverse muscle cryosections by means of indirect immunofluorescence microscopy. The SL was brightly stained, but considerable intracellular fluorescence was observed as expected from the biochemical analyses. Thus, the neutral GSL and ganglioside expression of the SL and the intracellular membraneous network is different in skeletal muscle both in terms of quantitative and qualitative GSL composition as demonstrated in details by means of biochemical and immunochemical techniques. The modulatory functions of GM3 and gangliosides of the neolacto- and ganglio-series towards the voltage dependent Ca(2+)-channel, largely preponderant in the triads-containing Tr/M fraction, is the subject of the accompanying paper (J. Müthing, U. Maurer, and S. Weber-Schürholz, Carbohydr. Res., 307 (1998) 147-157).
Animals↗
Comparative pathogenesis of haemorrhagic enteritis virus (HEV) infection in turkeys and chickens.
The pathogenesis of haemorrhagic enteritis virus (HEV) infection in chickens 3-4 days post-infection was compared with that in turkeys. As expected, infected turkeys showed HEV-specific lesions that included enlargement and mottling of the spleen, as well as haemorrhagic enteritis. In infected chickens, only splenomegaly was observed. The number of HEV-infected cells in the spleen was significantly (P < 0.05) higher in the turkey than in the chicken. In both species, the immunohistochemical labelling of B-cell surface determinants was diminished and the splenic B-cell areas were undetectable after HEV infection. Infection with HEV resulted in an increase in nitric oxide production by macrophages in chickens but not in turkeys.
Animals↗
Studies on 2-benzyloxy-4H-3,1-benzoxazin-4-ones as serine protease inhibitors.
The class of 3,1-benzoxazin-4-ones includes potent inhibitors of various serine proteases. Structural investigation on three 2-benzyloxy-4H-3,1-benzoxazin-4-ones (1-3) are described with respect to their reactivity to alkaline hydrolysis. The 13C NMR data of 2-benzyloxy-5-methyl-4H-3,1-benzoxazin-4-one 3 are discussed. This peri substituted compound was subjected to a crystal structure analysis. The heterocyclic skeleton together with the carbonyl oxygen and the methyl carbon is planar, and only small angle distortions occurred. The inhibition of neutrophil serine proteases by 1-3 is reported. The different reactivity of the 5-methyl derivative 3 towards serine proteases is mainly influenced by specific interactions within the active sites. Thus, 3 was found to rapidly acylate human leukocyte proteinase 3 and exhibited a Ki value of 1.8 nM.
Benzoxazines↗