Biomedical subjects
C Meyer
Publications and source records attributed to C Meyer.
Use of von Willebrand diseased kidney as donor in a pig-to-primate model of xenotransplantation.
BACKGROUND: The coagulation process in hyperacute and delayed xenograft rejection is essential and depends upon platelet adhesion and aggregation. The initial binding of platelets to the damaged endothelium is due to the interaction of the platelet receptor glycoprotein Ib with von Willebrand factor (vWF), which is present on activated endothelial cells and bound to the subendothelial matrix. We hypothesized that the use of organs from animals with homozygous von Willebrand disease (vWD), severely deficient in vWF, might prevent the thrombosis encountered in delayed xenograft rejection. METHODS: Ten baboons were treated by extracorporeal immunoadsorption of xenoreactive natural antibodies (XNA) through the donor pig liver to inhibit hyperacute rejection and received heterotopic vWD or control pig kidney xenografts. XNA levels, coagulation, and platelet activation markers were studied, and specimens of rejected kidneys were analyzed histologically. RESULTS: Although XNA depletion was comparable in both groups, neither kidney function nor survival times of control (n=5) or vWD (n=5) porcine kidneys showed any difference. Platelet and coagulation activation was evidenced in both groups after surgery and at rejection time. Immunohistochemical analysis revealed a weak endothelial vWF immunostaining in the rejected vWD kidneys, whereas it was undetectable in the nongrafted vWD kidneys, suggesting the deposition of baboon plasma vWF on the porcine vessels. CONCLUSIONS: The use of vWD organs did not improve the survival time of grafted kidneys in this xenotransplantation model. Further studies on the use of vWD organs, in association with other therapeutic approaches, such as complement inhibition, are nevertheless necessary to evaluate the usefulness of vWF deficiency as an adjunctive therapy to decrease the coagulation process during xenograft rejection.
The impact of emotion upon eating behavior: the role of subliminal visual processing of threat cues.
OBJECTIVE: Previous research has demonstrated that subliminal threat cues can influence eating behavior. The present study examined whether this effect is due to general emotional activation (by comparing positive and negative emotional cues), whether it is a product of specific negative emotional activation, and whether it can be achieved by activating appetite-related schemata. METHOD: One hundred women avoided food for at least 4 hr and then completed a task where they were exposed to one of five subliminal visual cues. The dependent variable was the amount eaten subsequently. RESULTS: Women who were exposed to the abandonment cue (lonely) ate significantly more than those who were exposed to the neutral cue (gallery), the positive emotional cue (happy), or the appetitive cue (hungry). Those with unhealthy eating attitudes also ate more after the hostile emotion cue (angry) than after the neutral cue. CONCLUSIONS: The results support cognitive models that stress an important role for threat processing in the facilitation of eating, rather than models advocating the centrality of food-related information. Abandonment schemata appear to be activated at an earlier stage than appetite-related schemata.
Enantiomeric composition of the polycyclic musks HHCB and AHTN in different aquatic species
Synthetic polycyclic musk fragrances are mainly represented by the compounds HHCB (Galaxolide(TM)) and AHTN (Tonalide(TM)). Because of their volume of use and their bioaccumulation potential, there is concern with respect to their environmental safety. HHCB and AHTN are chiral compounds, and gas chromatography using modified cyclodextrins as chiral stationary phases coupled to high-resolution mass spectrometry enabled enantioselective analysis even under unfavorable matrix conditions. The gas chromatographic elution order of (4S,7RS)- and (4R,7RS)-HHCB was assigned using synthetic (4S, 7RS)-HHCB. Fish and mussels reared in a pond associated with a municipal waste water treatment plant and semipermeable membrane devices exposed in the pond were analyzed for HHCB and AHTN. The highest lipid concentrations of HHCB and AHTN were observed in mussels (Dreissena polymorpha), tench (Tinca tinca), and crucian carp (Carassius carassius). Pronounced deviations in enantiomeric composition from racemic HHCB were observed in crucian carp and from racemic AHTN in tench. Correlations between lipid levels, enrichment, and enantioselective biotransformation of HHCB or AHTN were not seen. Selective biotransformation depended on both the compound and the species involved. The present study gives the first account of the enantiomeric composition of HHCB and AHTN in aquatic species. The lactone, 1,3,4,6,7,8-hexahydro-4,6,6,7,8, 8-hexamethylcyclopenta[g]-2-benzopyran-1-one, an oxidation product of HHCB, has been identified for the first time in environmental samples. Copyright 1999 Wiley-Liss, Inc.
Management of common bile duct stones in a single operation combining laparoscopic cholecystectomy and perioperative endoscopic sphincterotomy.
BACKGROUND: Laparoscopic cholecystectomy (LC) has become the reference treatment for biliary lithiasis, but the management strategy for common bile duct stones (CBDS) remains a subject of controversy in the absence of an established consensus. While conventional surgery remains the reference treatment for CBDS, minimally invasive techniques are becoming more and more popular. These methods consist of the extraction of the common bile duct stones either exclusively by laparoscopy or by sequential treatment with endoscopic sphincterotomy (ES) followed by LC. The aim of this study was to evaluate the treatment of CBDS in a one-stage operation by laparoscopic cholecystectomy (LC) and perioperative endoscopic sphincterotomy. PATIENTS AND METHODS: Between January 1994 and March 1998, 44 patients, 20 male and 24 female, (sex ratio 1.2) with a median age of 57 years (range 28-84 years) were treated for suspected or confirmed CBDS. The CBDS were uncomplicated in 39 cases (88%) and associated with a complication in 5 cases (12%), namely, cholangitis (2 cases) or acute pancreatitis (3 cases). The perioperative ES was performed immediately after the LC during the same operative time, with perioperative cholangiography being systematically performed (1 failure). In 6 cases, a transcystic drain was left in place (to ensure complete evacuation of the CBDS postoperatively) when there were more than three stones and/or when they were larger than 6 mm. The patient was positioned in the left lateral position in order to perform the ES. RESULTS: Mean operative time for LC was 60 min, range 40-90 min. The general anesthesia was prolonged by 40 min in order to perform an ES (range 30-60 min). The perioperative ES was unsuccessful in one case (2%), due to the impossibility of catheterizing the papilla, the preoperative MR cholangiogram being normal. Immediate clearance of the CBD was achieved in 95% of the cases (42 p). In 2 cases, residual stone was found in the sixth day after cholangiography and was spontaneously evacuated as shown by 21st-day control. There was no mortality or postoperative complications. The duration of the postoperative hospitalization was 4.6 days (range 3-6). CONCLUSIONS: We believe that LC combined with perioperative ES is a quick, reliable, and safe technique for the treatment of CBDS during a single operative procedure, although this approach is limited by the proximity and availability of an endoscopic team.
[Laparoscopic fundoplication for gastro-esophageal reflux. Multicenter study of 1,470 cases].
STUDY AIM: The aim of this multicenter retrospective study was to evaluate the immediate and 2-year results of the laparoscopic fundoplication for gastroesophageal reflux disease (GERD). PATIENTS AND METHODS: From 1992 to 1996, 1,470 laparoscopic fundoplications were performed for symptomatic GERD. Preoperative workup included upper GI tract endoscopy in 1,437 patients (97.7%), 24-hour pHmetry in 799 patients (54.3%) and esophageal manometry in 934 patients (63.5%). Four procedures were performed: Nissen, Nissen-Rossetti, Toupet and Toupet with cardiopexy. The results were estimated at 1 month and 3 months. The patients were examined or called 2 years after surgery in order to evaluate the functional results with Visick classification. RESULTS: Mean length of hospital stay was 4.6 days (range 2-48 days). Morbidity and mortality rates were 3.2% (47 patients) and 0.07% (1 patient) respectively. Conversion rate into laparotomy was 6.5% (96 patients). After 3 months, 87 patients (5.9%) had severe dysphagia and 91.9% of the patients were satisfied. At 2 years, 78 patients (5.6%) had a clinical recurrence. Five patients (0.35%) had a persistent dysphagia, 90 patients (6.5%) had secondary side effects; 38 patients had been reoperated; 92.7% of the patients were satisfied. There was no significant difference between the results of the four procedures, 3 months and 2 years after surgery. CONCLUSIONS: Laparoscopic fundoplication for treatment of GERD is a safe and effective procedure; 92.7% of the patients were satisfied 2 years after surgery.
Experimental animal myopia models are applicable to human juvenile-onset myopia.
Landmark explorations by Hubel and Wiesel investigating the importance of visual impressions in postnatal development of the visual system demonstrated that neural connections and eye growth can be affected by the absence of a clear retinal image during a critical period of postnatal development. Fundamental theories on neural plasticity and deprivation have recently been established that presume that a reduced quality of the retinal image during infancy and early childhood triggers an elongation of the posterior chamber of the eye, a so-called form deprivation myopia (FDM). In a retrospective multicenter study of 187 patients who suffered from phlyctenular keratitis with corneal opacification since early childhood, we reviewed data on gender, year and age at onset of the disease, refraction, and ultrasound biometry. Compared with the average refraction of +0.5 diopter (D) found in the general population, the mean refraction of -4.43 D that we found in our study demonstrated a marked shift toward myopia of almost 5 D. Patients with an early onset of phlyctenular keratitis had considerably higher myopia (-6.68 D) than those with a late onset (-1.67 D). Additionally, an axial elongation was confirmed by ultrasound biometry. Our average, axial length was 26.53 mm, compared with the epidemiologic mean of 24.00 mm. This myopic shift of 2.53 mm was caused mainly by an enlarged vitreous cavity. These results support the finding that blur can affect eye growth and lead to FDM not only in animal experiments but also in human beings.
Bilateral intracaudate cografting of fetal ventral mesencephalon and striatum in advanced Parkinson's disease.
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Constitutive protein expression of monocyte chemotactic protein-1 (MCP-1) by myelomonocytic cell lines and regulation of the secretion by anti- and proinflammatory stimuli.
We have investigated the protein expression of the chemokine monocyte chemotactic/chemoattractant protein-1 (MCP-1) in various human myelomonocytic leukemia cell lines. Applying specific ELISA, we demonstrated that this chemokine is produced constitutively by the cell lines HL-60, ML-2, MONO-MAC-6 and MUTZ-3 ranging between 440 and 1400 pg/ml MCP-1 per million cells. In the culture medium of two other unstimulated cell lines, MONO-MAC-1 and THP-1, almost no MCP-1 was detected. Stimulation of HL-60 and MONO-MAC-6 with lipopolysaccharide (LPS), and stimulation of ML-2 and MUTZ-3 with 12-tetradecanoyl phorbol 13-acetate (TPA) dramatically increased the MCP-1 level in the culture medium. The highest amount of MCP-1 (> 80 ng/ml within 24 h) was achieved by TPA stimulation of MUTZ-3 cells. Out of 15 cytokines tested for induction or enhancement of MCP-1 secretion, interleukin-3 (IL-3), IL-6, interferon-gamma (IFN-gamma), granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF) and tumor necrosis factor (TNFalpha) were able to augment (twofold to 12-fold) the MCP-1 level in the culture medium of MONO-MAC-6 cells. While the antinflammatory cytokines IL-4, IL-10 and IL-13 failed to suppress MCP-1 secretion, the glucocorticoid dexamethasone strongly inhibited the MCP-1 production of unstimulated and stimulated MONO-MAC-6 cells. Thus, several regulatory elements are involved in MCP-1 secretion. Despite the quantitative differences of MCP-1 production among the cell lines analyzed, our results demonstrated a constitutive secretion in differentiation-arrested myelomonocytic leukemia cell lines and emphasize the usefulness of these malignant cell lines as models to study MCP-1 secretion and regulation.
Occurrence of Isospora suis in larger piglet production units and on specialized piglet rearing farms.
Mixed fecal samples of 264 litters from five piglet production farms (155-238 sows/farm) were investigated three times during the suckling period for the occurrence of Isospora suis over the period of 1 year. On all five farms Isopora suis was found to be a common endoparasite with infection rates being highest in litters of 3-4 weeks of age. By the end of the third investigation period the cumulative infection rate was 53.8% of the litters ranging from 20.0% to 81.5% for the single farms. During the suckling period the infection rate increased from 18.6% to 32.6% and then to 37.7%. Diarrhea was present in 66.3% of the sampled litters with the highest rates at the end of the suckling period. 63.4% of the litters which showed diarrhea and 34.8% of those without diarrhea excreted I. suis within the study period. Diarrhea was recorded for 78.2% of the I. suis-positive litters and for 52.5% of the Isospora-negative litters. In summer and fall the occurrence of I. suis was higher (66.3% and 61.0%, respectively) than in spring and winter (47.7% and 37.9%, respectively). In litters with diarrhea and pathogenic E. coli I. suis often occurred simultaneously. Above-average hygiene measures and mainly perforated pen floors seemed to lower the risk of isosporosis. With the exception of Strongyloides ransomi other parasites were not found in the fecal samples of suckling piglets. Two specialized piglet rearing farms, a conventional large-scale rearing unit and a farm managed according to the segregated early weaning (SEW) system were examined three times during the 6-7 week rearing period. In both units I. suis was common, but was not correlated with diarrhea. In the SEW unit the infection rates decreased from 37.5% to 20.2% and to 4.1%, while the infection rate in the conventional unit slightly increased from the first (17.2%) to the second (21.9%) investigation and stayed at this level at the third sampling.
Gender differences in myocardial blood flow dynamics: lipid profile and hemodynamic effects.
OBJECTIVES: The purpose of the study was to compare myocardial blood flow (MBF) in hyperlipidemic postmenopausal women and age-matched hyperlipidemic men, and to analyze the relationship between cholesterol subfractions and myocardial blood flow in men and women. BACKGROUND: Women are protected from coronary artery disease (CAD) events until well after menopause, in part due to gender-specific differences in lipid profiles. METHODS: To examine the effect of these influences on coronary microcirculation, MBF was quantitated with N-13 ammonia/PET (positron emission tomography) at rest and during adenosine hyperemia in 15 women and 15 men, all nondiabetic, who were matched for age and total cholesterol levels (53+/-4 vs. 50+/-8 years, p = NS, 6.44+/-1.1 vs. 6.31+/-0.85 mmol/liter, or 249+/-41 vs. 244+/-33 mg/dl, p = NS). RESULTS: Women had significantly higher high density lipoprotein (HDL) and lower triglyceride (Tg) levels than did men, and they showed significantly higher resting MBF and stress MBF levels. Significant correlations were found between resting and hyperemic MBF and HDL and Tg levels (r = 0.44, p < 0.02 for stress MBF vs. HDL; r = 0.48, p < 0.007 for stress MBF vs. Tg). Gender was the strongest predictor of hyperemic MBF in multivariate analysis. Women responded to adenosine hyperemia with a significantly higher heart rate than did men, and hemodynamic factors correlated significantly with blood flow both at rest and during stress. CONCLUSIONS: These data suggest that the favorable lipid profile seen in women may be associated with preserved maximal blood flow in the myocardium.
Possible venous argon gas embolism complicating argon gas enhanced coagulation during liver surgery.
We report a case of a major venous argon embolism during argon beam coagulation of a liver biopsy. The essential signs were an abrupt reduction in end-tidal carbon dioxide partial pressure, in SpO2 and in systolic arterial pressure, at the time of coagulation. Spontaneous recovery was observed within 10 min. Precautions in respect of usage are highlighted.
Constitutive cytokine production by primary effusion (body cavity-based) lymphoma-derived cell lines.
Primary effusion lymphoma (PEL) is a new lymphoma entity occurring predominantly, but not exclusively in HIV+ patients with acquired immunodeficiency syndrome (AIDS). PEL grows exclusively in body cavities as serous lymphomatous effusion without evidence of mass disease or dissemination. The cells are infected with the newly discovered human herpesvirus-8 (HHV-8), often accompanied by co-infection with Epstein-Barr virus (EBV). Several lymphoma cell lines have been established from patients with AIDS- and non-AIDS-associated PEL. Given their phenotypical relationship to plasma cells, several cytokines may be important for growth and survival of PEL cells. We investigated the spectrum of cytokines produced by nine HHV-8+ PEL cell lines, in comparison with five Burkitt lymphoma, seven other B non-Hodgkin's lymphoma (B-NHL) and seven multiple myeloma-derived cell lines. In addition, we tested the response of the PEL cells to selected cytokines and the effects of neutralizing anti-cytokine and anti-cytokine receptor antibodies. Using specific ELISAs, PEL cell lines were found to produce large amounts of interleukin-6 (IL-6; 10-5000 pg/ml), IL-6 soluble receptor (IL-6sR; 30-600 pg/ml), IL-10 (600-80,000 pg/ml) and oncostatin M (OSM; 50-80 pg/ml) which in most cases were significantly higher than the levels produced by the Burkitt, B-NHL or myeloma cell lines; on the contrary, PEL cell lines did not elaborate significant levels of macrophage inhibitory protein (MIP-1alpha) and leukemia inhibitory factor (LIF). However, the levels of MIP-1alpha were increased 10- to 100-fold by treatment with phorbol ester TPA. PEL cell lines did not respond proliferatively to IL-6, IL-10, IL-11, LIF, MIP-1alpha, or OSM. Incubation with IL-6sR and IL-6 inhibited cell growth. Anti-IL6 neutralizing antibodies had no effect on PEL cell line proliferation; conversely, whereas anti-IL6R alone inhibited only weakly, anti-gp130 and anti-gp130 plus anti-IL6R showed strong inhibitory effects (>20% inhibition in 5/9 lines and >60% inhibition in 3/9 lines). In summary, PEL cell lines produce high amounts of cytokines (IL-6, IL-10, OSM); proliferation could be inhibited by blocking the receptors of the IL-6 signaling pathway.
Combination therapy of pentoxifylline and TNFalpha monoclonal antibody in dextran sulphate-induced mouse colitis.
BACKGROUND: Tumour necrosis factor-alpha (TNFalpha) has been suspected of playing an important role in the pathogenesis of inflammatory bowel diseases, and has become a target for the treatment of these diseases. Open-label, placebo controlled studies have shown that engineered CDP571 and chimeric anti-TNF antibody (cA2) provide a significant benefit in Crohn's disease. Since these antibodies have to be used repeatedly to maintain remission in inflammatory bowel disease, there is a concern that their use may compromise host defence and produce toxic side-effects. METHODS: We evaluated the combined use of mouse specific TNFalpha mab (25 microg/mouse, Endogen) and pentoxifylline (PF, 100 mg/kg/day, p.o., TNFalpha release inhibitor) in the DSS (3% dextran sulphate solution) model of mouse colitis. Colitis was induced by the feeding of 3% DSS for three cycles. The study groups were: Group I: single injection of rat anti-mouse IgG, Group II: single injection of TNFalpha mab, Group III: daily PF for three cycles, Group IV: single injection of TNFalpha mab + PF for three cycles, Group V: TNFalpha mab at the beginning of each cycle (three injections) and Group VI: TNFalpha mab (three injections) + daily PF for three cycles. Daily disease activity (DAI) was measured throughout the study. At the end of each cycle, colon tissue was processed for histology, myeloperoxidase (MPO) and plasma TNFalpha. RESULTS: Mice treated with a single injection of TNFalpha alone or TNFalpha mab + PF showed significantly lower DAI, inflammation scores and ulcer index compared with the IgG treated group. Mice treated with TNFalpha mab + PF had no ulcers. Multiple injections of TNFalpha mab or TNFalpha mab + PF showed greater inhibition in DAI and cytokines in the first two cycles. However, in the third cycle, multiple injections of TNFalpha mab showed adverse proinflammatory effects. CONCLUSION: The simultaneous administration of pentoxifylline and TNFalpha mab may enhance therapeutic outcomes in inflammatory bowel disease and reduce the side-effects associated with the repeated use of TNFalpha mab.
Farnesylation of Ras is important for the interaction with phosphoinositide 3-kinase gamma.
The correct functioning of Ras proteins requires post-translational modification of the GTP hydrolases (GTPases). These modifications provide hydrophobic moieties that lead to the attachment of Ras to the inner side of the plasma membrane. In this study we investigated the role of Ras processing in the interaction with various putative Ras-effector proteins. We describe a specific, GTP-independent interaction between post-translationally modified Ha- and Ki-Ras4B and the G-protein responsive phosphoinositide 3-kinase p110gamma. Our data demonstrate that post-translational processing increases markedly the binding of Ras to p110gamma in vitro and in Sf9 cells, whereas the interaction with p110alpha is unaffected under the same conditions. Using in vitro farnesylated Ras, we show that farnesylation of Ras is sufficient to produce this effect. The complex of p110gamma and farnesylated RasGTP exhibits a reduced dissociation rate leading to the efficient shielding of the GTPase from GTPase activating protein (GAP) action. Moreover, Ras processing affects the dissociation rate of the RasGTP complex with the Ras binding domain (RBD) of Raf-1, indicating that processing induces alterations in the conformation of RasGTP. The results suggest a direct interaction between a moiety present only on fully processed or farnesylated Ras and the putative target protein p110gamma.
Role of glutamine in human carbohydrate metabolism in kidney and other tissues.
Glutamine is the most abundant amino acid in the human body and is involved in more metabolic processes than any other amino acid. Until recently, the understanding of many aspects of glutamine metabolism was based on animal and in vitro data. However, recent studies using isotopic and balance techniques have greatly advanced the understanding of glutamine metabolism in humans and its role in glucose metabolism in the kidney and other tissues. There is now evidence that in postabsorptive humans, glutamine is an important glucose precursor and makes a significant contribution to the addition of new carbon to the glucose carbon pool. The importance of alanine for gluconeogenesis, viewed in terms of the addition of new carbons, is less than previously assumed. It appears that glutamine is predominantly a renal gluconeogenic substrate, whereas alanine gluconeogenesis is essentially confined to the liver. As shown recently, renal gluconeogenesis contributes 20 to 25% to whole-body glucose production. Moreover, glutamine has been shown not only to stimulate net muscle glycogen storage but also to stimulate gluconeogenesis in normal humans. Finally, in humans with type II diabetes, conversion of glutamine to glucose is increased (more so than that of alanine). The available evidence on the hormonal regulation of glutamine gluconeogenesis in kidney and liver and its alterations under pathological conditions are discussed.
Important role of the kidney in human carbohydrate metabolism.
Recent studies using a combination of isotope and balance techniques have shown that, in the postabsorptive state, the human kidney contributes substantially to overall glucose production and consumption. The kidney may contribute as much as the liver to gluconeogenesis and play an important role in the counterregulation of hypoglycemia. Furthermore, increased renal glucose production may contribute to fasting hyperglycemia found in type I and type II diabetes mellitus. Finally, loss of renal tissue as a consumer of glucose could explain the insulin resistance of uremia. We hypothesize that the human kidney may play a more important role in human carbohydrate metabolism than previously appreciated.
A conserved acidic motif in the N-terminal domain of nitrate reductase is necessary for the inactivation of the enzyme in the dark by phosphorylation and 14-3-3 binding.
It has previously been shown that the N-terminal domain of tobacco (Nicotiana tabacum) nitrate reductase (NR) is involved in the inactivation of the enzyme by phosphorylation, which occurs in the dark (L. Nussaume, M. Vincentz, C. Meyer, J.P. Boutin, and M. Caboche [1995] Plant Cell 7: 611-621). The activity of a mutant NR protein lacking this N-terminal domain was no longer regulated by light-dark transitions. In this study smaller deletions were performed in the N-terminal domain of tobacco NR that removed protein motifs conserved among higher plant NRs. The resulting truncated NR-coding sequences were then fused to the cauliflower mosaic virus 35S RNA promoter and introduced in NR-deficient mutants of the closely related species Nicotiana plumbaginifolia. We found that the deletion of a conserved stretch of acidic residues led to an active NR protein that was more thermosensitive than the wild-type enzyme, but it was relatively insensitive to the inactivation by phosphorylation in the dark. Therefore, the removal of this acidic stretch seems to have the same effects on NR activation state as the deletion of the N-terminal domain. A hypothetical explanation for these observations is that a specific factor that impedes inactivation remains bound to the truncated enzyme. A synthetic peptide derived from this acidic protein motif was also found to be a good substrate for casein kinase II.