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Biomedical subjects

A Paul

Publications and source records attributed to A Paul.

At least 163 records · Page 9Linked to original sources
PubMed1995

Overexpression of annexin V in cystic fibrosis epithelial cells from fetal trachea.

In this report, we investigated the expression of annexins I, II, V, and VI by Northern and Western blot analysis in four cell lines isolated from human fetal tracheae. Two cell lines were obtained from normal fetuses and the two others from fetuses with cystic fibrosis (CF). One CF fetus was heterozygous for the S549N and N1303K substitutions, whereas the other was homozygous for the delta F508 deletion. We found that the four annexins are always coexpressed. The expression of annexins I, II, and VI was the same in the four cell lines. In contrast, that of annexin V was significantly higher in CF than in normal cells. These observations demonstrate that annexins I, II, V, and VI are independently regulated in tracheal epithelial cell lines. Moreover, they suggest that the overexpressed annexin V, a Ca2+ channel, might profoundly modify Ca2+ transport across the membranes of CF cells.

Actins↗
PubMed1995

The E.A.E.S. Consensus Development Conferences on laparoscopic cholecystectomy, appendectomy, and hernia repair. Consensus statements--September 1994. The Educational Committee of the European Association for Endoscopic Surgery.

Under the mandate of the Educational Committee of the European Association of Endoscopic Surgery (E.A.E.S.), three consensus development conferences (CDCs) were performed in order to assess the current status of the endoscopic surgical approaches for the treatment of cholelithiasis, appendicitis, and inguinal hernia. Consensus panels for the different disease states (10-13 members each) selected by the education committee on the basis of members' clinical expertise, academic activity, community influence, and geographical location weighed the evidence on the basis of published results according to the criteria for technology assessment: feasibility, efficacy, effectiveness, economy. Draft statements were prepared, discussed by the panels, and presented at plenary sessions of the 2nd European Congress of the E.A.E.S. in Madrid September 15-17, 1994. Following discussions final consensus statements were formulated to provide specific answers for each topic to a minimum of the following questions: 1. What stage of technological development is the endoscopic surgical procedure at (in September 1994)? 2. Is endoscopic surgery safe and feasible? 3. Is it beneficial to the patients? 4. Who should undergo endoscopic surgery? 5. What are the training recommendations? Laparoscopic cholecystectomy is the procedure of choice for symptomatic cholelithiasis. Laparoscopic appendectomy is presently at the efficacy stage of development, because most of the data on feasibility and safety originate from centers with special interest in endoscopic surgery: it is not yet the gold standard for acute appendicitis. Endoscopic hernia repair is presently a feasible alternative for conventional hernia repair if performed by experienced endoscopic surgeons. It appears to be efficacious in the short-term. The full text of the consensus panel's statements is given in this publication.

Appendectomy↗
PubMed1995

Protein kinase C and tyrosine kinase pathways regulate lipopolysaccharide-induced nitric oxide synthase activity in RAW 264.7 murine macrophages.

1. In RAW 264.7 macrophages, lipopolysaccharide (LPS) and gamma-interferon (IFN gamma) alone or in combination stimulated the induction of nitric oxide synthase (iNOS) activity and increased the expression of the 130 kDa isoform of NOS. 2. LPS-induced NOS activity was reduced by incubation with CD14 neutralising antibodies and abolished in macrophages deprived of serum. 3. LPS stimulated a small increase in protein kinase C (PKC) activity in RAW 264.7 macrophages which was dependent on the presence of serum. However, IFN gamma did not potentiate LPS-stimulated PKC activity. 4. The protein kinase C inhibitor, Ro-318220, abolished both LPS- and IFN gamma-stimulated protein kinase C activity and the induction of NOS activity. 5. LPS- and IFN gamma-induced NOS activity was reduced by the tyrosine kinase inhibitor genestein. Genestein also reduced LPS-stimulated protein kinase C activity but did not affect the response to the protein kinase C activator, tetradecanoylphorbol acetate (TPA). 6. Nicotinamide, an inhibitor of poly-ADP ribosylation, abolished LPS- and IFN gamma-induced NOS activity. 7. Brefeldin A, an inhibitor of a factor which stimulates nucleotide exchange activity on the 21 kDa ADP-ribosylation factor, ARF, reduced LPS- and IFN gamma-induced NOS activity by approximately 80%. 8. These results suggest the involvement of protein kinase C, tyrosine kinase and poly-ADP ribosylation pathways in the regulation of the induction of nitric oxide synthase in RAW 264.7 macrophages by LPS and IFN gamma.

Adenosine Diphosphate Ribose↗
PubMed1995

CFTR gene transfer corrects defective glycoconjugate secretion in human CF epithelial tracheal cells.

We demonstrate that in immortalized normal human tracheal epithelial cells (NT-1 and 56FHTE8o-) 14C-labeled glycoconjugate secretion may be regulated independently by agonists of the protein kinase A (PKA) and protein kinase C (PKC) signaling pathways. In contrast, in immortalized cystic fibrosis (CF) human tracheal epithelial cells (CFT-1 and CFT-2), regulation is defective for agonists specific for the PKA but not for the PKC pathway. To characterize the involvement of the cystic fibrosis transmembrane conductance regulator (CFTR) in regulated glycoconjugate secretion, we examined the effect of adenovirus-mediated gene transfer of CFTR to CF and control cells. Forty-eight hours after infection, at a multiplicity of infection of 50 plaque-forming units per cell, high levels of CFTR mRNA were detected by reverse transcription-polymerase chain reaction, and de novo synthesis of CFTR protein was demonstrated by immunoblotting. Gene transfer to CF cells restored defective adenosine 3',5'-cyclic monophosphate (cAMP)-dependent secretion not only of chloride but also of glycoconjugates. Taken together, these results argue for a role for CFTR in cAMP-mediated glycoconjugate secretion.

Adenoviridae↗
PubMed1995

Ventilatory and pulmonary vascular response to hypoxia and susceptibility to high altitude pulmonary oedema.

Reduced tolerance to high altitude may be associated with a low ventilatory and an increased pulmonary vascular response to hypoxia. We therefore, examined whether individuals susceptible to acute mountain sickness (AMS) or high altitude pulmonary oedema (HAPE) could be identified by noninvasive measurements of these parameters at low altitude. Ventilatory response to hypoxia (HVR) and hypercapnia (HCVR) at rest and during exercise, as well as hypoxic pulmonary vascular response (HPVR) at rest, were examined in 30 mountaineers whose susceptibility was known from previous identical exposures to high altitude. Isocapnic HVR expressed as difference in minute ventilation related to difference in arterial oxygen saturation (delta V'E/ delta Sa,O2) (L.min-1/%) was significantly lower in subjects susceptible to HAPE (mean +/- SEM 0.8 +/- 0.1; n = 10) compared to nonsusceptible controls (1.5 +/- 0.2; n = 10), but was not significantly different from subjects susceptible to AMS (1.2 +/- 0.2; n = 10). Hypercapnic ventilatory response was not significantly different between the three groups. Discrimination between groups could not be improved by measurements of HVR during exercise (50% maximum oxygen consumption (V'O2,max)), or by assessing ventilation and oxygen saturation during a 15 min steady-state exercise (35% V'O2,max) at fractional inspiratory oxygen (FI,O2) of 0.14. Pulmonary artery pressure (Ppa) estimated by Doppler measurements of tricuspid valve pressure at an FI,O2 of 0.21 and 0.12 (10 min) did not lead to a further discrimination between subjects susceptible to HAPE and AMS with the exception of three subjects susceptible to HAPE who showed an exaggerated HPVR. It is concluded that a low ventilatory response to hypoxia is associated with an increased risk for high altitude pulmonary oedema, whilst susceptibility to acute mountain sickness may be associated with a high or low ventilatory response to hypoxia. A reliable discrimination between subjects susceptible to high altitude pulmonary oedema and acute mountain sickness with a low ventilatory response to hypoxia is not possible by Doppler echocardiographic estimations of hypoxic pulmonary vascular response.

Altitude↗
PubMed1995

[Laparoscopic surgery of ileus--miscarriage or training problem?].

The first results of laparoscopic surgery for mechanical ileus were analysed according to 3 classification systems of adverse perioperative events (complications). In our series 11 out of 14 patients were unsuitable for laparoscopic surgery mainly due to intraoperative mechanical problems. In 3 patients relevant and potentially hazardous events occurred which induced immediate conversion to laparotomy. Due to the impossibility and inability to completely explore the abdominal cavity, the laparoscopic approach cannot yet be recommended.

Adult↗
PubMed1995

Expression of cystic fibrosis transmembrane conductance regulator in human gallbladder epithelial cells.

BACKGROUND: Hepatobiliary complications in cystic fibrosis result predominantly from lesions of the biliary epithelium. These abnormalities affect the intrahepatic as well as extrahepatic bile ducts and the gallbladder. The protein cystic fibrosis transmembrane conductance regulator (CFTR), the gene product defective in cystic fibrosis, functions as a cAMP-activated chloride channel in the plasma membrane. As such, it may represent an important driving force for fluid transport across the epithelium. EXPERIMENTAL DESIGN: The purpose of this study was to investigate the expression of CFTR in human gallbladder epithelial cells and to examine the chloride ion transport properties of these cells. Immunolocalization was performed on tissue sections. The reverse transcription-PCR was used to analyze the expression of CFTR mRNA in freshly isolated and cultured gallbladder epithelial cells. The CFTR protein was detected by Western blotting and immunoprecipitation. The chloride ion transport properties of the cells were determined by 36Cl efflux studies. RESULTS: The CFTR protein was immunodetected in human gallbladder in situ and localized predominantly to the apical membrane of epithelial cells. High levels of CFTR mRNA and protein were maintained in gallbladder epithelial cells in primary cultured. Glycosylated forms of CFTR were present as confirmed by treatment with N-glycanase. Chloride efflux was stimulated by Ca(++)-dependent pathways but more intensely by cAMP-dependent pathways. Stimulation of chloride efflux by agonist of the cAMP-pathway was inhibited by diphenylamine carboxylic acid, a chloride channel blocker. Two physiologically active peptides--acting via cAMP, vasoactive intestinal peptide, and secretin--also stimulated chloride efflux in vitro. CONCLUSIONS: Our results are consistent with a high expression of endogenous functional CFTR protein in human gallbladder epithelial cells. Physiologically active peptides, vasoactive intestinal peptide and secretin, stimulate chloride conductance in these cells. These findings indicate that CFTR play an important role in the pathophysiology of the biliary epithelium, including the gallbladder epithelium.

Base Sequence↗
PubMed1995

Preoperative morbidity and anaesthesia-related negative events in patients undergoing conventional or laparoscopic cholecystectomy.

Laparoscopic cholecystectomy is the standard method for surgical treatment of non-malignant gall bladder disease. Well tolerated in otherwise healthy patients, it remains however, questionable whether the laparoscopic procedure in patients with severe pre-existing morbidity is associated with a higher incidence of negative intraoperative events than open cholecystectomy. Therefore, the incidence of negative intraoperative events was prospectively investigated in a series of 1,367 patients (319 with open cholecystectomy and 1,048 with laparoscopic cholecystectomy) who were analysed for occurrence of events such as hypertension, hypotension, arrhythmia, unusual bleeding and transfusion requirement, regurgitation or aspiration of gastric content and respiratory disorders. For further analysis the patients undergoing each operative procedure were divided into two subgroups with either preoperative ASA physical status I and II or III and IV. The study groups were comparable in sex and age. There were no intraoperative deaths. The frequency of hypertension, hypotension or arrhythmia alone and in combination was similar in both groups. The need for intervention was significantly more frequent in ASA class I/II patients with laparoscopic cholecystectomy. Respiratory disorders were rare. There was a significantly higher incidence of postoperative ventilatory support in patients with conventional cholecystectomy. Transfusion was required significantly less often in patients with laparoscopic cholecystectomy (0.19% versus 15.36%). CO2-pneumoperitoneum led to severe circulatory alterations in 7 healthy patients. The most severe negative event was a cardiac arrest in 1 female patient who was successfully resuscitated without any sequelae. In ASA-class III and IV patients intraoperative negative events were equally frequent and independent of the procedure. Severe preoperative morbidity per se seems to be no contraindication for laparoscopic cholecystectomy.

Adult↗
PubMed1994

Preoperative chemoradiation for adenocarcinoma of the pancreas and duodenum.

PURPOSE: This study was designed to evaluate the effects of preoperative chemoradiation on resectability, response, local control, and survival in patients with local or local-regional involvement from carcinoma of the pancreas or cancer of the duodenum and to assess the associated toxicity of such treatment. METHODS AND MATERIALS: This prospective pilot study of preoperative chemoradiation was initiated in 1986 for patients with clinical evidence of adenocarcinoma of the pancreas or duodenum without evidence of distant metastases. Radiation was given at 1.8 Gy per day to a total dose of 50.4 Gy. Two cycles of chemotherapy were given concurrent with radiation. On days 2-5 and 29-32, 5-fluorouracil (1 gm/m2/24 h x 4 days) was given, while mitomycin-C (10 mg/m2) was given on day 2 only. Surgical resection was 4-6 weeks following completion of chemoradiation. Thirty-one patients (17 male and 14 female) were entered on the protocol with a median potential follow-up of 4.5 years (range 6 months to 7.5 years). The median age was 64 years (range 32-73 years). Twenty-seven patients had pancreatic cancer (25 head, two body), while four patients had carcinoma arising from the duodenum. Twenty-one patients were initially judged to be unresectable and ten potentially resectable prior to chemoradiation. RESULTS: Twenty-nine of 31 patients completed the entire course of radiation and both cycles of chemotherapy. Acute toxicity from chemoradiation consisted of nausea, vomiting, diarrhea, stomatitis, or hematologic suppression which was moderate to severe (Grade 3 or 4) in seven patients (23%). One patient died of sepsis following the first week of therapy. Seventeen patients (55%) underwent curative resection with subtotal or total pancreatectomy or Whipple resection (four duodenum, 13 pancreas) and two (2/17) had pathologic nodal involvement, while (0/17) none had involved margins. A complete pathologic response was seen in all four (4/4) patients with duodenal cancer and in none (0/13) with pancreatic cancer who underwent resection. The median postoperative hospitalization stay was 22 days (range 4-144 days). Of 17 patients who underwent curative resection, there were two postoperative mortalities (12%). Late complications have included abscess, one; and nonmalignant ascites, five. Ten of the 31 patients are alive. For patients with pancreatic cancer the median survival is 9 months, while survival at 1 year and 3 years are 36% and 19% overall and 60% and 43% at 1 and 3 years for those undergoing resection. Six of the 27 patients (22%) with pancreatic cancer are alive without recurrence. All four patients with duodenal cancer are alive without recurrence (12 months, 23 months, 35 months, 90 months). CONCLUSION: Preoperative chemoradiation for cancer of the pancreas and duodenal region was relatively well-tolerated and enhanced resectability and downstaging of nodal metastases were suggested. The 3-year survival, particularly in patients who underwent resection, was high. For these reasons the applicability of this treatment regimen for pancreatic cancer is presently being studied in a group-wide multi-institutional Phase II trial. Chemoradiation for duodenal cancer has produced a complete pathologic response in all patients and survival has been excellent, suggesting efficacy of this regimen for duodenal cancer.

Adenocarcinoma↗
PubMed1994

Randomized trial of modified Bassini versus Shouldice inguinal hernia repair. The Cologne Hernia Study Group.

Between 1986 and 1992, 265 men of mean age 51 (range 16-75) years with a primary inguinal hernia were randomized to undergo surgery by staff surgeon or surgical resident and further randomized to receive a modified Bassini operation (transversalis fascia not divided but included in the repair) or Shouldice procedure. The follow-up rate was 92.1 per cent with a mean follow-up of 3.3 years. Recurrence developed in 12 of 125 patients with a Bassini procedure and two of 119 after a Shouldice repair (9.6 versus 1.7 per cent, P = 0.006). The recurrence rate was no different for staff surgeons and trainees (5.9 versus 5.6 per cent, P not significant). Multivariate analysis identified the presence of a direct hernia (P = 0.003) as the additional main factor for the development of recurrence.

Adolescent↗
PubMed1994

Phosphorylation of vimentin is an intermediate step in protein kinase C-mediated glycoconjugate secretion.

We have previously shown that fibroblasts from patients with cystic fibrosis (CF) display a higher response to 4 beta-phorbol 12-myristate 13-acetate (PMA) than control fibroblasts for stimulation of both protein kinase C (PKC) cytosol-to-membrane translocation and glycoconjugate secretion. In this study we took advantage of these cells with differential responsiveness to PMA to investigate the endogenous substrate(s) involved in PKC stimulation of glycoconjugate secretion after verification of cystic fibrosis transmembrane conductance regulator gene expression in control and CF fibroblasts. We show that a 57-kDa protein that was associated with cytoskeleton and was identified as vimentin by immunoblotting emerged as a good candidate for mediating PKC stimulation of glycoconjugate secretion. 1) Its phosphorylation by PMA was abolished by PKC inhibition or depletion. 2) In both control and CF fibroblasts, the PMA-induced increase in its phosphorylation preceded the phorbol ester stimulation of glycoconjugate secretion. 3) For both processes, the concentration-response curves were superimposable, with higher maximal levels for CF fibroblasts relative to controls. 4) PMA-stimulated 57-kDa protein phosphorylation, like PMA-stimulated glycoconjugate secretion, was significantly increased by Ca2+. 5) Increased PMA phosphorylation of the 57-kDa protein as a result of okadaic acid inhibition of intracellular phosphatases was reflected in increased PMA stimulation of glycoconjugate secretion. In conclusion, 1) PMA phosphorylation of a cytoskeletal 57-kDa protein, identified as vimentin, appears to be an intermediate step in PKC stimulation of constitutive glycoconjugate secretion in human skin fibroblasts; and 2) this process is impaired in CF disease.

Base Sequence↗
PubMed1994

Identification of decorin proteoglycan in bovine tracheal serous cells in culture and localization of decorin mRNA in situ.

Bovine tracheal submucosal gland serous cells in culture synthesize and secrete proteoglycans and not mucin glycoconjugates. We are interested in the characterization and role of these proteoglycans in airway secretions. The major [35S]methionine-labeled proteoglycan present is identified as the small chondroitin/dermatan sulfate proteoglycan decorin (PG II. PG40). Consistent with its identity as decorin this proteoglycan showed average apparent molecular weights of 75,000 to 130,000 with a core protein of an average, M(r) of about 40,000 and with glycosaminoglycan chains sensitive to chondroitinase ABC lyase of an average M(r) of about 25,000. These data were obtained from gel chromatographic and SDS-PAGE analyses. Northern blot analysis and partial amino acid sequencing of the purified protein further confirmed its identity as decorin. In situ hybridization studies using a decorin riboprobe revealed no expression of decorin in the surface epithelium and only low levels of expression in submucosal gland epithelial cells of bovine tracheal tissue. However, high levels of expression were localized to cells which are peripheral to tracheal submucosal gland epithelial cells and which contact with the extracellular matrix.

Amino Acid Sequence↗