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Biomedical subjects

P Rocmans

Publications and source records attributed to P Rocmans.

At least 37 records · Page 2Linked to original sources
PubMed1997

Diversity and prevalence of somatic mutations in the thyrotropin receptor and Gs alpha genes as a cause of toxic thyroid adenomas.

A total of 33 different autonomous hot nodules from 31 patients, originating mainly from Belgium, were investigated for the presence of somatic mutations in the TSH receptor and Gs alpha genes. This constitutes an extension of our previous study, including the first 11 nodules of the series. The complete coding sequence of the TSH receptor gene and the segments of Gs alpha known to harbor mutations impairing guanosinetriphosphotase activity were studied by direct sequencing of genomic DNA extracted from the nodules. DNA from the juxtanodular tissue or peripheral white blood cells was analyzed in all patients to confirm that the mutations identified were somatic. Twenty-seven mutations (82%) were found in the TSH receptor gene, affecting a total of 12 different residues or locations. All these mutations but 2 (see below) have been identified previously as activating mutations. Only 2 mutations were found in Gs alpha (6%). In 4 nodules, no mutation was detected. Five residues (Ser281, Ile486, Ile568, Phe631, and Asp633) were found mutated in 3 or 4 different nodules, making them hot spots for activating mutations. Phe631 and Asp633 belong to a cluster of 5 consecutive residues (629-633) in the N-terminal half of transmembrane segment VI; which harbor together 44% of the mutations identified in this cohort. Two novel mutations were identified: a point mutation causing substitution of Phe for Leu at position 629 (L629F); and a deletion of 12 bases removing residues 658-661 at the C-terminal portion of exoloop 3 (del658-661). When tested by transfection in COS-7 cells, both mutant receptors display increase in constitutive stimulation of basal cAMP accumulation. Although it is still capable of binding TSH, the del658-661 mutant has completely lost the ability to respond to the stimulation by the hormone. Our results demonstrate that, in a cohort of patients from a moderately iodine deficient area, somatic mutations increasing the constitutive activity of the TSH receptor are the major cause of autonomous hot nodules.

Adenoma↗
PubMed1996

Regulation and metabolic role of phospholipase D activity in human thyroid and cultured dog thyrocytes.

The actions of TSH, ATP, the ionophore A23187, the endoplasmic reticulum Ca(2+)-ATPase inhibitor thapsigargin, and phorbol dibutyrate (PDBu) on 3H-cytidine-monophosphate phosphatidic acid (3H-CMP-PA) accumulation were studied in human thyroid slices to evaluate PA generation and inositol recycling towards phosphatidyl-inositol synthesis. The effects of the same agonists also were measured on phosphatidylbutanol (PtdBut) generation in 3H-palmitate or 3H-myristate prelabeled slices to assess the activity of phospholipase D (PLD). The phospholipid target of this PLD was determined on 3H-choline prelabeled human thyroid slices by measuring 3H-choline release in incubation medium and slices and 3H-choline incorporation in phospholipids. TSH (10 U/L) stimulated 3H-CMP-PA accumulation in an LiCl-and propranolol-insensitive way, as well as 2H-fatty acids incorporation into PA, diacylglycerol, and phosphatidylcholine (PtdCho) with on evidence of dose-dependent effects and had no detectable action on PLD activity. The effects of TSH were not reproduced by Bu2cAMP or forskolin. Thapsigargin and A23187 both increased CMP-PA accumulation and PtdBut generation, whereas ATP only stimulated PLD activity. The phorbol ester PDBu (5 x 10(-7) mol/L) increased PtdBut formation and 3-H-fatty acid incorporation into PtdCho, but had no effect on CMP-PA generation. Staurosporine (STSP) (5 x 10(-6) mol/L), a nonspecific inhibitor of protein kinase C, unexpectedly reproduced the effects of PDBu. The increase of 3H-choline in slices' supernatant and the decrease of 3H-choline-labeled PtdCho induced by PDBu, ATP, thapsigargin, and STSP indicate that the activated PLD hydrolyzed PtdCho. We suggest that the PA generation induced by PLD stimulation could contribute to the stimulated H2O2 formation and iodide organification observed with the agonists inducing PtdBut accumulation. Indeed, Bu2cAMP and forskolin, known to decrease iodide organification in human thyroid, inhibited the PLD stimulation induced by ATP and PDBu. In cultured dog thyrocytes, phorbol esters, and STSP induced DNA synthesis and dedifferentiation, whereas thapsigargin inhibited TSH-induced growth and killed phorbol esters stimulated cells, suggesting a positive role of PLD stimulation towards dedifferentiated growth and of simultaneously raised [Ca2+)i and stimulated protein kinase C-PLD towards growth arrest and cellular death.

Adenosine Triphosphate↗
PubMed1995

CT-guided percutaneous drainage of an anterior mediastinal abscess with a 16 F catheter.

We report a case of anterior mediastinal abscess treated by percutaneous drainage under computed tomography (CT) guidance. The relationships of the abscess to the adjacent organs were clearly delineated by an intravenous injection of contrast material, and the drain was inserted between the sternum and the vasa thoracica interna. Selection of this route and the choice of a large-bore catheter (16 F) are discussed.

Abscess↗
PubMed1994

On-line expiratory flow-volume curves during thoracic surgery: occurrence of auto-PEEP.

Flow-volume loops were monitored continuously in 39 patients undergoing thoracic surgery requiring one-lung ventilation. In 26 of the 39 patients (67%), auto-positive end-expiratory pressure (auto-PEEP) was seen on the flow-volume curves during both two-lung and one-lung ventilation. Eighty-seven percent of the patients whose trachea was intubated with a smaller size (35- and 37-French gauge) double-lumen tracheal tube exhibited auto-PEEP, compared with patients in whom the tube used was larger (39- or 41-French gauge: 54% and 50%, respectively). Before operation, mean airway resistance was significantly greater in patients who exhibited auto-PEEP during anaesthesia (2.4 cm H2O litre-1 s) than in patients without auto-PEEP (1.7 cm H2O litre-1 s).

Adult↗
PubMed1993

Postoperative radiotherapy after pneumonectomy: impact of modern treatment facilities.

PURPOSE: The present study was undertaken to see how modern treatment facilities, computed tomography (CT)-based treatment planning and linear accelerator, have modified the results of postoperative irradiation after a pneumonectomy for lung cancer. METHODS AND MATERIALS: Between 1970-1985, 103 patients were treated in our department after a pneumonectomy: 50 patients with a T1T2N0 tumor and 53 patients with a T3, N1 or N2 tumor. Three groups were considered: 27 patients had only surgical resection, 51 patients were irradiated postoperatively with a Co60 source, and 25 patients were treated using those modern facilities. RESULTS: The 5-year survival varies from 4% to 31% according to the tumor extent but also to the radiation technique. Patients treated with a Co60 source had a dismal 5-year survival rate (8%) whereas patients treated with the modern facilities had a 5-year survival rate of 30% similar to the 31% of the control surgical group including less advanced tumors. CONCLUSION: Linear accelerator and computed tomography-based treatment planning improved the accuracy of postoperative thoracic irradiation and allow to deliver high doses to the mediastinum even after a pneumonectomy.

Combined Modality Therapy↗
PubMed1993

Ploidy level and proliferative activity measurements in a series of 407 thyroid tumors or other pathologic conditions.

This study describes the ploidy level and proliferation rate in a series of 74 multinodular goiters (MNGs), 17 cases of Hashimoto's disease, 33 cases of Basedow's disease, 113 adenomas, 139 primary carcinomas, and 31 cervical lymph node metastases from 376 patients. Both ploidy level and proliferation rate were assessed by digital cell image analyses of Feulgen-stained nuclei from formalin-fixed, paraffin-embedded tissues. The ploidy level of each sample was assessed using both its DNA index and its DNA histogram type. The proliferation index assessments corresponded to the determination of the proportion of cells in the S-phase fraction. The data reveal that the proportion of aneuploid cases increases according to the following sequence: simple MNGs and normomacrovesicular adenomas-->MNGs with adenomatous hyperplasia and microvesicular adenomas and Hürthle cell adenomas-->papillary and Hürthle cell carcinomas-->follicular and medullary carcinomas-->anaplastic carcinomas. This suggests the preneoplastic nature of the microvesicular adenomas and even of MNGs with adenomatous hyperplasia. The ploidy levels of 99% of the 407 cases of the thyroid tumor series could be described using six DNA histogram types: diploid, hyperdiploid, triploid, hypertriploid, tetraploid, and polymorphic. It was possible to assess the proliferation rate of 279 samples. The results show that a significantly higher proportion of malignant compared with benign thyroid tumors (35.5% v 10.5%, respectively) exhibited a proliferation index higher than 5%, and that, whether benign or malignant, the hypertriploid thyroid tumors proliferated significantly less than the nonhypertriploid thyroid tumors.

Cell Division↗
PubMed1991

Pulmonary sequestration-like anomaly presenting as a spontaneously resolving mass.

A premature baby boy presented at birth with respiratory distress. A right lower lobe opacity was found on chest X-ray. Pulmonary sequestration was the diagnosis suggested by ultrasound. The size of the mass decreased on subsequent examinations. 4 months later X-rays and sonography failed to demonstrate any remaining mass. This case illustrates another example of involutive pathology and suggests that not all pulmonary sequestration-like anomalies should be operated on.

Bronchopulmonary Sequestration↗
PubMed1991

Unlike thyrotropin, thyroid-stimulating antibodies do not activate phospholipase C in human thyroid slices.

The effects of thyroid-stimulating antibodies (TSAb) and of thyrotropin (TSH) were compared, on the generation of cyclic AMP and inositol phosphates (InsP), in human thyroid slices incubated in vitro, and on the Rapoport cyclic AMP bioassay. The TSAb positive sera were obtained from 19 patients with Graves' disease. In 14 experiments with the slices system, TSH significantly increased cyclic AMP accumulation (TSH, 0.03-10 mU/ml) as well as the cyclic AMP-independent inositol trisphosphate (InsP3) generation (TSH, 1-10 mU/ml). In the same 14 experiments, TSAb (0.10-28 mg/ml) enhanced cyclic AMP intracellular levels as expected while they did not induce any InsP accumulation. Even when TSAb increased cyclic AMP levels to the same or higher values as those obtained with TSH concentrations allowing InsP3 generation. TSAb were still unable to activate the phosphatidylinositol-Ca2+ cascade. The patterns of the response curves of TSAb and TSH on cyclic AMP accumulation were different, suggesting that different mechanisms may be involved. In addition, unlike TSH, TSAb were not able to stimulate H2O2 generation, which in human tissue mainly depends on the activation of the phosphatidylinositol-Ca2+ cascade. Immunoglobulins from six additional Graves' patients lacking measurable cyclic AMP-stimulating activity in both slices and cells systems did not activate phospholipase C either. In conclusion, our results show that TSAb do not share all the metabolic actions of TSH on human thyroid tissue. The data provide support for the concept that the pathogenesis of Graves' disease can be fully accounted for by the ability of TSAb to stimulate adenylate cyclase. This work also confirms that TSH activates the cyclic AMP and the phosphatidylinositol cascade by independent pathways in the human thyroid.

Adolescent↗
PubMed1990

[NMR evaluation of neoplastic invasion of the pulmonary artery].

Bronchial tumors that invade the mediastinum are not necessarily inoperable. Whether surgery is possible depends, among other things, on the extent of pulmonary artery invasion. The authors have studied the value of cardiac-gated MRI and compared it with CT and venous DSA for staging tumor invasion. CT demonstrated the areas of contact between tumor and mediastinum. The MRI planes were transverse and also in the main axis of the pulmonary arteries. Twenty-one patients were studied and in 16 the findings could be checked during surgery. In all cases the findings on MRI were confirmed. In eight patients MRI provided more information than CT and DSA combined and thereby showed its superiority for evaluating arterial invasion.

Adenocarcinoma↗
PubMed1990

The biochemistry of autonomous thyroid nodules: clues on the pathogenesis.

The "in vitro" characteristics of H2O2 generation, iodide, cAMP and PI metabolism, have been compared in tissues from autonomously functioning thyroid nodules and their quiescent counterpart to test the hypothesis that autonomy may result from constitutive activation of the tissue's TSH-IP's, or TSH-cAMP regulatory pathway. The enhanced iodide uptake is entirely due to increased transport capacity, the affinity of iodide transport and the fractional binding of iodide to protein remaining unchanged. The basal IP's accumulation is slightly higher in seven cases where it was studied but the response to TSH was markedly decreased. The cAMP-protein phosphorylation regulatory axis is not constitutively activated. Under TSH and forskolin stimulation, a 20K protein is not phosphorylated in nodular tissue as it is in its quiescent counterpart. The others, possible points of deviation in the cAMP cascade, studied in these tissues, i.e. basal cyclic AMP, desensitization to TSH, iodide inhibition, responses to other hormones or neurotransmitters were not systematically different in nodular tissue. The 20K protein, not phosphorylated in response to TSH in the nodules, could represent an absent negative controlling element. The absence of a 20K protein substrate of cAMP dependent protein kinases remains the most interesting clue about the mechanism of autonomy. We are now trying to purify and clone this protein.

Adenylyl Cyclases↗
PubMed1990

[Long-term survival after surgery of solitary cerebral metastasis of lung cancer. Clinical case and review of the literature].

In cases of solitary brain metastasis of lung cancers other than small cell lung carcinoma, which has an even poorer prognosis, long-term patient survival over 1.2 years is rare. One case with a 12 year survival is presented. The authors review the other 18 cases with a minimum 5 year survival described in the literature. It is concluded that surgical aggressivity is justified in these cases.

Brain Neoplasms↗
PubMed1990

[Aspergillus colonization of a pulmonary sequestration. Apropos of a case associated with erythema nodosum].

We describe a case of interlobar pulmonary sequestration diagnosed at thoracotomy in which there were a number of unusual features at presentation: an opacity with multiple cavities, positive aspergillus precipitins, erythema nodosum and a haemothorax complicating a trans-thoracic needle biopsy. Although it is unusual to find such a constellation of symptoms and signs they could be explained in a logical fashion.

Aspergillosis↗
PubMed1989

Resection of lung metastases from sarcomas.

Between 1977 and 1987, 19 patients were candidates for resection of lung metastases from pretreated extrathoracic primary tumours. Primary tumours comprised 10 osteosarcomas, one Ewing sarcoma and eight soft tissue sarcomas. All 19 patients presented with metachronous metastases. Twenty-eight thoracotomies were performed in these 19 patients. Nine patients underwent multiple surgical explorations. All the metastases were removed by wedge resection. Seven out of 10 patients treated for osteosarcoma received pre- and postoperative chemotherapy, and three out of 10 postoperative chemotherapy only. The projected survival rate at 3 years is 33%. Seven out of 19 patients survived more than 2 years; four of them were free of disease at 33, 54, 56 and 137 months. Good prognosis appears to be long metastases-doubling time, metachronous metastases, small number of lung metastases, pathological evidence of tumour necrosis and/or fibrosis after chemotherapy and, of course, complete control of the primary tumour and no extrathoracic metastases.

Adolescent↗