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O Huber

Publications and source records attributed to O Huber.

At least 37 records · Page 2Linked to original sources
PubMed1996

A role for cadherins in tissue formation.

We have produced null mutant mouse embryonic stem cells for the cell adhesion molecule E-cadherin. Such E-cadherin-/- ES cells are defective in cell aggregation; this defect can be corrected by transfection with cDNA for either E-cadherin or N-cadherin driven by a constitutive promoter. The presence (or absence) of E-cadherin regulates the expression of the transcription factor T-brachyury, indicating that cadherins play a role in linking cell surface receptors and gene expression. Comparative analysis of the parental and the genetically altered ES cell lines was performed to examine cell differentiation and the capability to form organized tissues. While differentiating E-cadherin-/- ES cells are still able to express various early and late differentiation markers, they show a clear-cut deficiency in forming organized structures. This phenotype can be rescued by constitutive expression of E-cadherin, which results exclusively in formation of epithelia. In contrast, rescue transfectants expressing N-cadherin show no epithelial structures, instead forming neuroepithelium and cartilage. These results provide the first evidence that specific cadherins directly stimulate differentiation into certain types of tissues.

Animals↗
PubMed1996

[Follow-up and results of liver transplantation for primary biliary cirrhosis].

Primary biliary cirrhosis is regarded as one of the optimal indications for orthotopic liver transplantation in adults. With the decrease in the operative mortality, the analysis of the potential long-term complications including disease recurrence is becoming increasingly relevant. The purpose of this study was to evaluate the long-term results of liver transplantation for primary biliary cirrhosis in our center. From 1988, 14 patients were transplanted for this indication and all of them were alive with a mean follow-up of 43 months by the end of June 1995. At that time, all complications related to chronic liver disease were reversed by the transplant except for osteopenia. Lumbar column fractures and overweight were the major inconveniences encountered. Hypertension and diabetes related to antirejection therapy disappeared during the first year of follow-up in all but one patient. Recurrence of the disease was not encountered in this series where a triple association of immunosuppressive therapy was maintained in each patient. At long-term, the frequency of disease recurrence in the liver allograft seems quite low and even in this situation immunosuppressive agents may alter the evolution of the disease. All patients (n - 12) who had at least 1 year of follow-up had a normal level of bilirubin and their quality of life was good to excellent. These results, confirmed by the international experience, support the notion that patients suffering from primary biliary cirrhosis should be transplanted as early as complications from this chronic liver disease occur.

Adult↗
PubMed1995

Orthotopic liver transplantation in hemophilia B: a case report.

Liver transplantation is a treatment modality that is being used with increasing frequency in cases of liver-based metabolic defects. This is a case report of a patient with hemophilia B who was treated since childhood with factor IX replacement for recurrent hemarthroses. Subsequent hepatitis B (HBV) and C (HCV) infection had resulted in the development of chronic active hepatitis, ultimately leading to cirrhosis. Orthotopic liver transplantation performed for endstage liver disease resulted in a rise in factor IX levels from 2% to 83% of normal values within 24 h postoperatively, and levels remained above 90% of normal values after postoperative day 3 without factor IX replacement. To our knowledge, only two cases of hemophilia B treated by orthotopic liver transplantation have been reported. This procedure has, however, only been implemented in cases of terminal liver insufficiency in hemophiliacs.

Blood Component Transfusion↗
PubMed1995

Immunocytochemical distribution of E-cadherin in normal and injured lung tissue of the rat.

Affinity purified rabbit anti-mouse E-cadherin antibodies, reacting with diverse rat epithelia, were used to characterize epithelial changes in a radiation-induced fibrosis model of rat lung by immunoblotting techniques, immunoperoxidase and immunofluorescence microscopy. Immunostaining of normal rat lung tissues revealed a predominant staining of type II pneumocytes. Immunoelectron microscopy confirmed the immunohistochemical data of normal lung tissue obtained at the light microscopic level. In severely injured rat lung, we found enhanced immunoreactivity for E-cadherin at the surface of type I alveolar epithelial cells. The results suggest that E-cadherin is an adhesion molecule that is modulated after pathological alteration of the alveolar epithelium and that the antiserum may be useful for the characterization of normal and diseased rat epithelia.

Animals↗
PubMed1994

[Results of liver transplantations in Geneva or 32 consecutive transplantations without mortality in 2 years].

Between 1 january 1992 and 31 december 1993, 32 liver transplantations were performed in 29 patients (5 transplants in 3 children and 27 transplants in 26 adults) at Geneva University Hospital. Despite 5 super-urgent transplantations (3 fulminant hepatitis, 1 end-stage Wilson disease and 1 primary nonfunction), all patients are still alive and all have lived more than 10 months. On 1 october 1994, all patients were at home and 93% were in good general condition. No patient of this series had been transplanted for cancer and all patients positive for hepatitis B surface antigen receive long-term administration of anti-HBs immune globulin: in this respect, the long-term mortality risk of the present series of patients seems to be very low. Although these results highlight that liver transplantation can be performed safely by a competent medico-surgical team, two significant difficulties have to be outlined. First, patients are likely to die on the waiting list due to unavailable grafts, especially in emergency cases. Second, the postoperative period of patients with decompensated end-stage liver disease at the time of liver transplantation is still one of high morbidity. These facts underline that chronic liver disease patient should be evaluated for liver transplantation prior to the terminal decompensated stage of the disease, when the candidate's invariably poor general condition precludes successful liver transplantation.

Adolescent↗
PubMed1994

Algal-CAMs: isoforms of a cell adhesion molecule in embryos of the alga Volvox with homology to Drosophila fasciclin I.

Proof that plants possess homologs of animal adhesion proteins is lacking. In this paper we describe the generation of monoclonal antibodies that interfere with cell-cell contacts in the 4-cell embryo of the multicellular alga Volvox carteri, resulting in a hole between the cells. The number of following cell divisions is reduced and the cell division pattern is altered drastically. Antibodies given at a later stage of embryogenesis specifically inhibit inversion of the embryo, a morphogenetic movement that turns the embryo inside out. Immunofluorescence microscopy localizes the antigen (Algal-CAM) at cell contact sites of the developing embryo. Algal-CAM is a protein with a three-domain structure: an N-terminal extensin-like domain characteristic for plant cell walls and two repeats with homology to fasciclin I, a cell adhesion molecule involved in the neuronal development of Drosophila. Alternatively spliced variants of Algal-CAM mRNA were detected that are produced under developmental control. Thus, Algal-CAM is the first plant homolog of animal adhesion proteins.

Alternative Splicing↗
PubMed1994

[Prevention of viral recurrence following liver transplantation for post-hepatitis B and B-delta cirrhosis].

The incidence of recurrence of hepatitis B virus (HBV) following orthotopic liver transplantation (OLT) is as high as 80% when no attempt at prevention has been considered. HBV reinfection is associated with the reappearance of hepatitis B surface antigen (HBsAg) and HBV DNA in serum and, in most cases, with rapid severe graft damage. Immunoprophylaxis using polyclonal anti-HBs immunoglobulins reduces the risk of recurrence but this long-term therapy remains highly expensive. In this report, we use fresh frozen plasma (FFP) with high titers of anti-HBs immunoglobulins in an attempt to reduce HBV recurrence. From July 1987 to September 1993, 11 patients underwent OLT for HBV-related liver disease (18% of our OLT patients). FFP were administered to 6 patients continually for 7 to 46 months. Only one patient, under long-term immunosuppressive treatment before OLT, was reinfected 7 months after OLT. Rapid development of graft failure was observed with histologic manifestations of a fibrosing cholestatic hepatitis, leading to patient death after 12.5 months with concomitant bacterial infection. In this protocol, the rate of reappearance of HBsAg was 17%, a figure which can be favorably compared with other reports. All patients were subsequently tested for HCV and HIV and remained negative. In conclusion, FFP with high titers of anti-HBs immunoglobulins is at least as effective as polyclonal anti-HBs immunoglobulins in reducing the rate of HBV recurrence following OLT. The estimated cost of this new immunoprophylaxis method is less than 10% of the classical prophylaxis based on purified human polyclonal anti-HBs immunoglobulins.

Graft Rejection↗
PubMed1994

Prospective randomized comparison of imipenem monotherapy with imipenem plus netilmicin for treatment of severe infections in nonneutropenic patients.

Nosocomial pneumonia and sepsis, as well as severe diffuse peritonitis, must be treated early in order to prevent complications such as septic shock and organ dysfunctions. With the availability of new broad-spectrum and highly bactericidal antibiotics, the need of combining beta-lactams with aminoglycosides for the treatment of severe infections should be reassessed. A prospective randomized controlled study was performed to compare imipenem monotherapy with a combination of imipenem plus netilmicin in the empiric treatment of nosocomial pneumonia, nosocomial sepsis, and severe diffuse peritonitis. A total of 313 patients were enrolled, and 280 were assessable. The antibiotic treatment was successful in 113 of 142 patients (80%) given the monotherapy and in 119 of 138 patients (86%) given the combination (P = 0.19). The failure rates for the most important type of infection, i.e., pneumonia, were similar in the two groups, as well as the number of superinfections. While creatinine increase was associated with factors not related to antibiotic therapy for all eight patients of the monotherapy group, no factor other than the antibiotics could be found for 6 of the 14 cases of nephrotoxicity observed in the combination group (P = 0.014). Finally, the emergence of Pseudomonas aeruginosa resistant to imipenem occurred in 8 monotherapy patients and in 13 combination therapy patients. In conclusion, imipenem monotherapy appeared as effective as the combination of imipenem plus netilmicin for the treatment of severe infection. The addition of netilmicin increased nephrotoxicity, and it did not prevent the emergence of P. aeruginosa resistant to imipenem.

Adult↗
PubMed1993

Levodropropizine reduces capsaicin- and substance P-induced plasma extravasation in the rat trachea.

We investigated the effect of the non-opioid, peripherally acting antitussive agent levodropropizine to reduce neurogenic plasma extravasation in the rat trachea. Levodropropizine (10, 50 and 200 mg/kg) reduced in a dose-dependent manner the extravasation of Evans blue dye evoked by capsaicin. Levodropropizine inhibited also substance P-evoked extravasation, whereas it did not affect the extravasation evoked by platelet activating factor. Levodropropizine (10 and 100 microM) did not affect the contraction produced by [Sar9,Met(O2)11]substance P, a selective agonist for tachykinin NK1 receptors, in the rat urinary bladder in vitro. These data indicate that levodropropizine inhibits capsaicin-induced plasma extravasation: (a) acting at a postjunctional level; (b) exhibiting neuropeptide selectivity and; (c) via a mechanism independent of tachykinin NK1 receptor blockade. Irrespective of the mechanism, this novel antiinflammatory action of levodropropizine underlines its potential role in inflammatory airway diseases such as bronchial asthma.

Animals↗
PubMed1993

Tachykinins mediate contraction of the human lower esophageal sphincter in vitro via activation of NK2 receptors.

The contractile response to natural tachykinins and selective peptide agonists for tachykinin receptors was studied in strips of circular smooth muscle of human lower esophageal sphincter in vitro. The effects of phosphoramidon, which inhibits neutral endopeptidase (EC.3.4.24.11) and of the non-peptide compounds, SR 48968 and CP-96,345, which selectively block NK1 and NK2 receptors, respectively, were also investigated. Substance P, neurokinin A and neurokinin B produced a concentration-dependent contractile response. The rank order of potency was neurokinin A > neurokinin B > substance P. Phosphoramidon (1 microM) potentiated the response to substance P without changing the order of potency of natural tachykinins. The NK2-selective agonist, ([ beta Ala8]neurokinin A-(4-10)), produced a concentration-dependent contraction. The NK1 ([Sar9,Met(O2)11]substance P, 1 microM) and NK3 ([MePhe7]neurokinin B, 1 microM) selective agonists, however, did not exert any contractile effect. The selective NK2 antagonist, SR 48968, potently inhibited in a concentration-dependent (10 nM-1 microM) manner the response to neurokinin A, without affecting the response to carbachol. The selective NK1 antagonist, CP-96,345 (1 microM), did not affect the response to neurokinin A. These results indicate that tachykinins contract the circular muscle of human lower esophageal sphincter, and that this effect is mediated by NK2 receptor stimulation. Moreover, a phosphoramidon-sensitive mechanism plays a role in the regulation of the response to substance P.

Benzamides↗
PubMed1993

Unexpectedly high rate of phlebographic deep venous thrombosis following elective general abdominal surgery among patients given prophylaxis with low-molecular-weight heparin.

One hundred ninety-four patients undergoing elective general abdominal surgery were randomized in a single-blind study to receive one daily subcutaneous injection of a low-molecular-weight heparin, dalteparin sodium (2500 IU, n = 97) or nadroparin calcium (3075 IU, n = 97), two regimens that are approved in Europe to prevent deep venous thrombosis. On the eight postoperative day, bilateral ascending leg phlebography (n = 185) showed the presence of deep venous thrombosis in 45 cases (24.3%; 95% confidence interval, 18% to 31%), with a significantly higher rate (on intention-to-treat) among the patients who received the lower dosage (30 vs 15 deep venous thromboses). We conclude that the two regimens of low-molecular-weight heparin that were used in this study failed to prevent postoperative phlebographically proved deep venous thrombosis in one of four patients.

Abdomen↗
PubMed1993

Tachykinins contract the circular muscle of the human esophageal body in vitro via NK2 receptors.

BACKGROUND: The action of tachykinins in the circular muscle of the human esophageal body is not known. The present study aimed to determine the response to tachykinins and the receptor type mediating this response. METHODS: Specimen were obtained from organ donors or patients undergoing esophagectomy for cancer, and isometric tension in response to tachykinins was measured. RESULTS: Substance P (SP), neurokinin A (NKA), and neurokinin B (NKB) evoked a concentration-dependent contraction with the following order of potency: NKA > NKB > SP. The neutral endopeptidase inhibitor, phosphoramidon, increased only the response to SP. [beta Ala8]NKA(4-10), a selective agonist of the NK2 receptor, produced a concentration-dependent contraction, whereas [Sar9,Met(O2)11]SP and [MePhe7]NKB, selective agonists of NK1 and NK3 receptors, respectively, had no effect. Contraction evoked by NKA was inhibited by the nonpeptide NK2 antagonist SR 48968 but not by the nonpeptide NK1 receptor antagonist CP-96,345, tetrodotoxin, or atropine. SR 48968 did not affect the response to carbachol. CONCLUSIONS: Tachykinins contract the circular muscle of human esophageal body by activation of NK2 receptors without involvement of neural mechanisms. Response to SP is modulated by a phosphoramidon-sensitive enzymatic activity.

Adolescent↗
PubMed1993

Characterization of tachykinin receptors in ferret trachea by peptide agonists and nonpeptide antagonists.

The tachykinin receptors mediating mucus secretion and smooth muscle contraction were studied in the ferret trachea in vitro. Substance P (SP) and the selective agonist for NK1 receptor ([Sar9,Met(O2)11]SP), but not selective agonists for NK2 ([Ala5,beta-Ala8]neurokinin A-(4-10)) and NK3 ([MePhe7]neurokinin B) receptors, induced secretion of macromolecules in a concentration-dependent fashion. The nonpeptide NK1 receptor antagonist, CP-96,345, but not the nonpeptide NK2 receptor antagonist, SR-48968, inhibited SP-induced secretion. Both neurokinin A (NKA) and [Ala5,beta-Ala8]NKA-(4-10), but not NK1 and NK3 selective agonists, evoked a concentration-dependent smooth muscle contraction. SR-48968, but not CP-96,345, inhibited in a concentration-dependent manner the response to NKA. CP-96,345 and SR-48968 did not affect the concentration-dependent increase in macromolecule secretion or smooth muscle contraction by carbachol. These findings indicate that NK1 receptors mediate secretion of macromolecules and NK2 receptors mediate smooth muscle contraction, in response to tachykinins in the ferret trachea in vitro.

Animals↗
PubMed1993

Traumatic paramediastinal air cyst: report of two cases and review of the literature.

Two cases of traumatic paramediastinal air cyst are presented with a review of the literature. This rare condition affects young people and usually occurs on the left side of the chest. Its course is spontaneously benign. Although they are usually easily diagnosed on chest roentgenograms, these cysts may sometimes be difficult to differentiate from other more serious traumatic lesions. Computed tomography (or a contrast swallow roentgenogram in some instances) can elucidate doubtful cases.

Adult↗
PubMed1992

Polypeptide marker and disease patterns found while mapping proteins in ascitis.

To assess the protein composition of ascitis, 28 samples of ascitic fluid were obtained from patients admitted to Geneva University Hospital. The samples were analysed randomly and blindly by high-resolution two-dimensional polyacrylamide gel electrophoresis. The final visual evaluation was compared with the discharged summary and diagnosis. The protein pattern of ascitis was, as expected, very similar to normal or diseased plasma, with the exception of two spots which were present in ascitic fluids but not in the 200 plasma samples analyzed in parallel. After microsequencing, they proved to be beta-fibrinogen fragments. Several diseases showed distinct patterns, especially acute pancreatitis. A group of intense spots with an apparent molecular mass between those of alpha 1-antitrypsin and beta-haptoglobin were found in all ascitic fluid from pancreatitis cases (six patients). These spots had isoelectric points similar to those of alpha 1-antitrypsin and beta-haptoglobin and microsequencing revealed that they were three different fragments of alpha 1-antitrypsin.

Acute Disease↗
PubMed1992

Value of liquid crystal contact thermography and plasma level of D-dimer for screening of deep venous thrombosis following general abdominal surgery.

Because the use of radioactive fibrinogen uptake test (FUT) has become questionable both for ethical (risk of virus transmission) and technical (lack of sensitivity) reasons, we investigated the potential value of two alternative methods for screening of asymptomatic deep venous thrombosis following elective digestive surgery: liquid crystal contact thermography (LCCT) and measurement of plasma concentration of D-dimer (DD), as compared with bilateral ascending phlebography. Out of 194 patients, 185 underwent phlebography on the 8th (0-19, median and range) postoperative day. Despite prophylaxis with low-molecular-weight heparin and elastic stockings, DVT was detected on phlebography in 58 legs of 45 patients. Sensitivity of LCCT with respect to the presence of DVT was 55% (n = 184 patients) or 28% (n = 368 legs) with a specificity of 67% and 82%, respectively. These poor performances were obtained despite a good interobserver agreement for the LCCT assessments (overall kappa coefficient of 0.66 between three experts). The most accurate cut-off of DD for discriminating patients with or without DVT was 3,000 micrograms/l, as determined by ROC curve analysis. Sensitivity of a DD level of more than 3,000 micrograms/l for the presence of phlebographically documented DVT on the 8th postoperative day was 89% for a specificity of 48%. Thus, LCCT cannot be used for screening of postoperative, mainly asymptomatic DVT following general surgery. On the other hand, measurement of plasma DD may be useful for initial screening, a negative result (level less than 3,000 micrograms/l) allowing to exclude DVT (negative predictive value of 93%) and a positive result (positive predictive value of 35%) requiring confirmation by phlebography.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

[Liver transplantation for primary biliary cirrhosis].

Primary biliary cirrhosis (PBC) is regarded as one of the optimal indications for orthotopic liver transplantation (OLT) in adults. Between July 1987 and August 1991, 7 patients had PBC as the indication for OLT. 6 were transplanted and one patient is still on the waiting list. The patients' mean age was 47 years (range: 39 to 59) and the time from diagnosis to indication for OLT was 4, 7, 8, 10, 12, 15 and 17 years. Variceal hemorrhage episodes treated by sclerotherapy (plus porta-caval shunt in one patient) occurred in 3 patients before OLT. All suffered from jaundice (mean bilirubin 232 mumol/l, range 116 to 536), weakness, anorexia and pruritus. There were no deaths in this series during a mean follow-up time of 26 months (range 6 to 43). With the exception of osteopenia, all complications of chronic liver disease were reversed by OLT. Despite numerous postoperative problems (e.g. reoperations, intense rejection episodes, cytomegalovirus infections and lumbar column fractures), the quality of life is excellent for these 6 patients. Mean bilirubin at time of last follow-up was 18 mumol/l (range 8 to 26). No evidence of PBC recurrence was found. Based on international experience confirmed by this series, we support the notion that no patient suffering from advanced PBC should be denied OLT whenever possible.

Adult↗