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Biomedical subjects

A Paul

Publications and source records attributed to A Paul.

At least 199 records · Page 11Linked to original sources

Pericellular glycoconjugates of cultured fibroblasts from control and cystic fibrosis patients.

1. Labeled glycoconjugates released by trypsin from cell surfaces of control and cystic fibrosis (CF) skin fibroblasts were purified and fractionated by column chromatography on Sephadex G-50 and Concanavalin A Sepharose. Based on chemical analysis and specific enzymatic digestions: (1) Glycoconjugates were characterized as O-linked glycopeptides consisting predominantly of glycosaminoglycan type and N-linked glycopeptides with glycans of complex type. Their relative proportions were similar between the two groups. (2) The N-linked glycopeptides exhibited an increased molar ratio of fucose to galactose in CF fibroblasts. (3) When pericellular glycoconjugates were metabolically labeled with [14C]glucosamine and [3H]fucose, incorporation and degradation kinetics were similar between the two groups.

Carbohydrates↗

Regulation of secretion in cultured tracheal serous cells by protein kinases A and C.

We recently reported that cultured gland serous cells release chondroitin sulfate proteoglycans (CSPGs) in response to beta-adrenergic agonists. In this study, we analyzed this regulatory pathway and other cellular mechanisms responsible for CSPG secretion. We show the following. 1) Isoproterenol increased CSPG secretion in a concentration-dependent manner, with maximal stimulation (50%) obtained at 10(-5) M; at this concentration, the beta-agonist also stimulated protein kinase A (PKA) by 50%, whereas it increased cellular adenosine 3',5'-cyclic monophosphate (cAMP) content by 300%. 2) Phenylephrine (10(-5) M), 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (1.6 x 10(-7) M), and A23187 (10(-6) M) also stimulated CSPG secretion; this stimulation was concomitant with protein kinase C (PKC) translocation from cytosol to membrane, was blocked by sphingosine (2 x 10(-5) M), and was additive with that elicited by isoproterenol. 3) All PKC activators potentiated the isoproterenol-induced increased in cAMP accumulation without modifying the activation of PKA elicited by the beta-agonist. Our results indicate that although the signaling pathways triggered by alpha- and beta-adrenergic agonists converge at the level of adenylate cyclase in tracheal serous cells, PKA and PKC independently regulate CSPG secretion.

Animals↗

[Dyspepsia and food intolerance in symptomatic gallstone disease. Does cholecystectomy help?].

60 patients with symptomatic gallstone disease were asked about their abdominal symptoms and food intolerance. Equally a healthy control group was investigated. Preoperatively, 72% of patients with gallstones suffered from right upper quadrant pain. Additionally all patients complained of associated dyspeptic symptoms (100% vs. 8% of the control group). 51% of patients with gallstone disease vs. 15% of the control group avoided flatulent and fatty food. 4 months after cholecystectomy, 90% were painfree, 82% were free of dyspeptic symptoms and 84% were not complaining of any food intolerance. 6% developed new food intolerances. Thus cholecystectomy seems to be an effective treatment, not only for typical gallstone related symptoms, but also for associated symptoms, such as dyspepsia and food intolerance. Different therapeutic regimens have to compete with these results.

Adult↗

The reversibility of impaired mucociliary function after lung transplantation.

Impairment of mucociliary function occurs after lung transplantation and may predispose patients to repeated pulmonary infections. The purpose of this study is to determine whether and how soon such mucociliary function may recover. Ten dogs underwent left lung autotransplantation. Within 3 weeks five of these dogs underwent study for proximal airway clearance by observation through a bronchoscope of the movement of carbon particles placed at different locations on the tracheobronchial mucosa. The mechanical properties of collected mucus from specific sites were determined by magnetic rheometry. The right lung, which was not operated on, served as a paired control. Similar studies were conducted in the remaining five dogs at 12 weeks after autotransplantation. Lung autotransplantation caused significant depression of proximal airway clearance and a 35% increase in mucous rigidity (p = 0.05) soon after operation. At 12 weeks after operation, there was a partial recovery of proximal airway clearance. Mucous changes were no longer consistent. Histologic and electron microscopic examinations initially revealed focal denudation of ciliated cells and loss of the bronchial glands. At 12 weeks there was a regeneration of cilia and a reappearance of the bronchial glands. We conclude that the mucociliary function, observed to be depressed early after lung autotransplantation, recovers partially during the late postoperative period. Thus the mucociliary functional recovery should be attributed to revascularization rather than to reinnervation, since the latter is unlikely to occur during this period.

Anastomosis, Surgical↗

Fimbrial phase variation in Bordetella pertussis: a novel mechanism for transcriptional regulation.

Fimbriae belong to a class of extracellular filamentous proteins which are involved in the attachment of bacteria to host tissues. Bordetella pertussis, the etiological agent of whooping cough, produces two serologically distinct fimbriae. We show that, like a number of other B. pertussis virulence genes, transcription of the fimbrial subunit genes (fim) is positively controlled by trans-acting polypeptides encoded by the bvg locus. In addition to this coordinate control, transcription of the fim genes is regulated at an individual level by phase variation. This process is characterized by a switching between a high and low level of expression of a particular fim gene. We have identified a conserved DNA region, located close to the start of the fim genes, which is likely to be involved in both positive regulation by the bvg locus, and phase variation. This promoter region contains a stretch of approximately 15 C residues and it appears that phase transitions occur by small insertions or deletions in this C-rich region. We propose that these mutations affect transcription of the fim genes by varying the distance between the binding site for an activator and the -10 box. The fim promoter shows homology with the pertussis toxin promoter, which is also positively regulated by the bvg locus.

Base Sequence↗

Further evidence for abnormal protein kinase C regulation of macromolecule secretion in fibroblasts from cystic fibrosis patients.

In comparison to skin fibroblasts from normal subjects, those from patients with cystic fibrosis (CF): (1) bound [20-3H] phorbol 12,13-dibutyrate (PDBu) with a higher affinity Kd = 25.8 vs 12.8 nM respectively) but expressed a similar number of total phorbol ester binding sites (about 2.5 pmol PDBu bound/mg of protein); (2) exhibited a faster and higher response to 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA) for the stimulation of [35S]-labelled glycoconjugate release, but were equally sensitive to the synergistic effect of A23187 on this process; and (3) secreted glycoconjugates with similar [35S]-sulfate and [14C]-leucine to [14C]-glucosamine labelling ratios. Taken together, these results provide further evidence for abnormal protein kinase C (PKC) regulation of macromolecule secretion in CF disease.

Binding Sites↗

[Percutaneous endoscopic tracheostomy].

Between 6/88 and 8/89 61 critically ill patients (sepsis, ARDS, pneumonia, multiple trauma, etc.) underwent elective percutaneous endoscopic tracheostomy (PET). Following dilation up to 36 Fr. a number 6-10 tracheostomy tube was introduced. The patients were ventilated 17 (2-68 days) before and 28 (4-160) days after PET. One patient died from cardiac arrest, and in 4 patients, because of tube obstruction or cuff defect, reintubation was necessary. Additionally 2 significant infections and a minor bleeding and a emphysema occurred. Elective percutaneous tracheostomy performed in the ICU seems to be a simple and cost-effective procedure.

Coma↗

Endoscopic guided percutaneous tracheostomy: early results of a consecutive trial.

Percutaneous tracheostomy is increasingly being used for patients needing prolonged ventilatory support. The purpose of this study was to assess the feasibility of widespread application of endoscopic guided percutaneous tracheostomy. Sixty-one consecutive ICU patients requiring prolonged mechanical ventilation underwent bedside endoscopic guided percutaneous tracheostomy. Using a modified Ciaglia technique, a #6-10 tracheostomy tube was introduced between the second and third tracheal rings. Bronchoscopic transillumination facilitated identification of the appropriate tracheostomy site, and verified satisfactory placement of dilators and tracheostomy tube. There was one procedure-related death due to arrhythmia. Procedure-related complications included (n = 7): bleeding (controlled with local pressure), two infections, two cuff tears, and two obstructions of the tracheal tube. The tracheostomy was eventually removed in 13 patients. Bronchoscopic evaluation of three patients at 4 months post-tracheostomy removal was normal and there has been no clinical evidence suggestive of tracheal stenosis in the remaining ten extubated patients. There was a 50% reduction in cost when compared to operative tracheostomy. Percutaneous tracheostomy is a simple, safe, cost-effective bedside procedure for critically ill ventilator-dependent patients. Endoscopic guidance appears to increase the safety of this procedure and may prevent complications of pneumothorax, subcutaneous emphysema, and paratracheal false passage previously reported with blinded percutaneous methods.

Adult↗

Percutaneous endoscopic tracheostomy.

Bedside percutaneous tracheostomies are increasingly performed. This avoids patient transport to the operating room. Complications of this procedure are largely related to the blind nature of the technique. After laboratory studies, 4 patients underwent percutaneous endoscopic guided tracheostomy in a selective clinical trial. There were no procedure-related complications. Endoscopic guidance ensures precise low tracheostomy position, prevents paratracheal tube misplacement, and avoids inadvertent injuries.

Endoscopy↗

[Indications for construction of stoma pouches].

Despite the advances of reconstructive surgical techniques, there are still indications for enterostoma constructions. Terminal colostomies are constructed after abdominoperineal rectal amputations. The terminal ileostomy is the procedure of choice after total colectomies for Crohn's disease. Loop colostomies are still a possibility for stool diversion procedures and for decompression in acute colonic obstruction. Loop ileostomies reduce load before ileal anastomoses and are increasingly used as diverting stomas in cases of colonic anastomoses. The cecal tube fistula, which does not divert the fecal stream completely, has the special advantage of easy, spontaneous closure.

Colostomy↗

Does the addition of albumin to the prime solution in cardiopulmonary bypass affect clinical outcome? A prospective randomized study.

Colloid solution is commonly used to increase the oncotic pressures of priming solutions used in the cardiopulmonary bypass circuit. To study the effectiveness of this practice, we prospectively randomized 100 adult patients undergoing cardiac operations to receive Ringer's lactate solution plus 50 gm of albumin (group A) or Ringer's lactate solution alone (group B) as the prime solution for the bypass circuit. Personnel involved in the management of these patients were blinded concerning the group to which the patients had been randomized. Forty clinical parameters related to perioperative fluid balance, cardiopulmonary function, and renal function were studied. Although group B received a larger volume of crystalloid solution intraoperatively (p less than 0.05), had a lower mean cardiac filling pressure (p less than 0.05), and had a higher hematocrit value (p less than 0.05) in the immediate postoperative period, all mean values for both groups were within the normal range. There were no differences between the two groups with regard to postoperative clinical parameters of cardiopulmonary and renal function, nor was outcome affected by the addition of albumin to the prime solution. We conclude that there is no clinically detectable advantage for the practice of adding 50 gm of albumin to the priming solution of bypass circuits in adults undergoing cardiac operations. Routinely supplementing the bypass prime solution with albumin adds significant cost, estimated to be approximately $10,000 per 100 cases, without demonstrable clinical benefits. Whether this practice can be of value in selected cases needs to be further studied.

Albumins↗

Does the surgical trauma of "exploratory thoracotomy" affect survival of patients with bronchogenic carcinoma?

A retrospective review was carried out to assess the possible adverse immunosuppressive effect of exploratory thoracotomy on the survival of patients with non-small cell carcinoma of the lung with N2 nodal metastases. Between 1960 and 1982, 48 patients with non-small cell bronchogenic carcinoma underwent exploratory thoracotomy; lung resection was not done because mediastinal lymph nodes were involved. The survival of these patients was compared with that of 64 patients in whom N2 disease was established by mediastinoscopy alone and who did not undergo thoracotomy. There were no significant differences with respect to age, sex, tumour type and adjunctive radiotherapy. There were slightly more T4 tumours in the thoracotomy group (50% versus 30%). The hospital stay was longer in the thoracotomy group (2.3 +/- 1.1 versus 1.5 +/- 0.9 months [mean +/- SD]). However, follow-up studies showed that, although these patients had a more traumatic procedure, the actuarial survival curves for the two groups were virtually identical, and the 12-month survival rates were less than 20% for both groups. The median survival was 6.0 months for the thoracotomy group and 7.0 months for the mediastinoscopy group. These findings failed to demonstrate an adverse immunosuppressive effect of thoracotomy on lung cancer patients.

Adult↗

Mucociliary function in autotransplanted, allotransplanted, and sleeve resected lungs.

Tracheobronchial mucociliary function in dogs that underwent left upper sleeve lobectomy was compared with that of dogs that underwent left lung autotransplantation or allotransplantation (n = 5 each). Proximal airway clearance was measured by observing the movement of carbon particles through a bronchoscope. Preoperative and postoperative clearance rates for the right lungs in these dogs were unchanged. Although preoperative clearance rates in the transplanted left lungs were comparable with those of the right lungs, these left lungs were unable to clear the carbon particles during a 15-minute observation period 3 weeks postoperatively. In contrast, preoperative and postoperative clearance rates for the dogs that underwent sleeve resection were unchanged for both lungs. Mucus rigidity was studied by microrheometry and was found to be significantly increased postoperatively for samples collected from the autotransplanted and allotransplanted lungs than for samples collected from the untreated right lungs. These changes in mucus were noted for forces representing both normal ciliary beat and coughing. Viscoelastic properties of mucus were not significantly altered after sleeve lobectomy. Microscopic study showed squamous cell metaplasia and relative disappearance of bronchial glands distal to the anastomosis in all transplanted lungs. These changes were less pronounced in the sleeve resected bronchi. We conclude that changes in rheologic characteristics of mucus can impair mucociliary clearance and may be related to denervation after lung transplantation. Bronchial devascularization may have an additional effect of altering mucosal structures and function in the early postoperative period after lung transplantation. These effects are avoided by preserving peribronchial tissue in sleeve resection.

Animals↗