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P Berger

Publications and source records attributed to P Berger.

At least 37 records · Page 2Linked to original sources
PubMed2003

[Anti-IgE and future treatments for respiratory allergies].

Immediate hypersensitivity remains the fundamental mechanism of respiratory allergy, emphasizing the importance of the antigen-immunoglobulin (IgE) reaction. Development of innovating treatments has naturally centered on a search for compounds inhibiting the IgE response, in particular anti-IgE antibodies. Humanized anti-IgE antibodies have been recently developed for administration in humans. These antibodies are designed to form complexes with circulating IgE which can be eliminated. The first trials have demonstrated an efficacy in allergic asthma, expressed by a significant decrease in consumption of systemic steroids in severe asthma. Other work has also showed a lower number of hospitalizations for acute asthma. Other therapeutic approaches have focused on limiting the production of IgE by an effect on the auxiliary lymphocyte balance, or more generally, by inhibiting the Th2 response while favoring the Th1 response. Early results obtained with anti-IL-5 were disappointing since the decrease in the eosinophilic response was not associated with any alteration in bronchial hyperreactivity. Administration of IL-12 has given similar results but the first trials with nebulized anti-IL-4 are more promising.

Antibodies, Anti-Idiotypic↗
PubMed2002

Oxidation of amino groups by hydroxyl radicals in relation to the oxidation degree of the alpha-carbon.

Nitrogen organic compounds constitute a large class of aqueous pollutants. These compounds include not only azoic structures, nitrogen heterocycles, and nitrous groups but also amides and amines. This work consisted in studying the OH* induced oxidation of simple primary amines in dilute aqueous solution with special attention to mineralization of the nitrogen group as a function of the nature of the alpha-carbon. H2O2/UV and gamma-irradiation processes were used for the production of OH* radicals, and the molecules studied were one alpha-amino acid i.e., glycine (HOOCCH2NH2), and two primary amides i.e., acetamide (CH3CONH2) and oxamic acid (HOOCCONH2). It was shown that the oxidation of glycine leads to the formation of ammonia, whereas the acetamide molecule is first oxidized into oxamic acid ending in complete mineralization with production of nitrates. Reaction mechanisms are proposed which account for the observed inorganic nitrogen end product depending on the oxidation degree of the carbon atoms of the molecules. It follows that the present study will allow for prediction of the fate of nitrogen resulting from the oxidation of primary amino groups by OH* radicals.

Amines↗
PubMed2002

Passive sensitization of human airways induces mast cell degranulation and release of tryptase.

BACKGROUND: This study was designed to examine the effect of passive sensitization (PS) on human bronchial mast cells. PS with asthmatic serum induces a hyper-responsiveness to nonspecific agonists, and immunoglobulin (Ig)E binding mainly on mast cells. METHODS: Bronchi dissected out from 19 lung specimens were incubated in normal or asthmatic serum. Immunohistochemistry was performed using monoclonal antibodies (MoAbs) directed against tryptase, chymase, or c-kit. Mast cells were classified as fully granulated (type I), partly (type II) or largely degranulated (type III). Tryptase was measured in supernatant using ELISA. Contractile response was recorded in a separated set of experiments using an organ bath system. RESULTS: PS decreased both tryptase positive cells (47.9 +/- 10.0 vs. 26.7 +/- 4.8 cell/mm2, P = 0.003) and chymase positive cells (26.1 +/- 3.3 vs. 14.9 +/- 1.8 cell/mm2, P = 0.01), but did not alter the number of c-kit positive cell. PS decreased the proportion of type I (55.4 vs. 28.9%, P < 0.0001) and, concomitantly increased that of types II (23.2 vs. 41.0%, P < 0.0001) and III (21.4 vs. 30.1%, P = 0.04). Following PS, tryptase concentration significantly increased and the magnitude of histamine response, was correlated with the amount of type II mast cells. CONCLUSION: PS of human isolated bronchi induces a mast cell degranulation related to in vitro hyper-responsiveness, along with a tryptase release.

Asthma↗
PubMed2002

[The pathophysiological role of smooth muscle cells in bronchial inflammation].

Airway smooth muscle cells (SMC) have been implicated in the pathophysiology of bronchial inflammation. SMC can be considered a target of the inflammatory reaction. This cell-type is capable of contraction, proliferation and mediator synthesis in response to various stimuli, in particular those associated with the inflammatory reaction. SMC can also be considered as an inflammatory cell-type. Cytokines and adhesion molecules released by SMC have an autocrine action and paracrine action on other cell-types, particularly those involved in inflammation, inducing chemotactism and cell adhesion. This interaction allows SMC to directly act on cells such as the T-lymphocyte, the eosinophil and the mast cell. SMC could therefore be a potential target of anti-inflammatory treatment.

Asthma↗
PubMed2001

Estradiol decreases the acetylcholine-elicited airway reactivity in ovariectomized rats through an increase in epithelial acetylcholinesterase activity.

Estrogen replacement therapy (ERT) is frequently prescribed for postmenopausal women. Epidemiological data suggest that sex hormones may play a role in the expression of asthma, but the mechanism(s) whereby this influence is mediated remain(s) unclear. To better understand the role of physiologic doses of estrogens in airway function, we tested the hypothesis that 17beta-estradiol (E(2), 10 microg/kg per d for 21 d) given to oophorectomized female rats modifies airway responsiveness to cholinergic agonists, compared with oophorectomized rats given placebo. In vivo, the concentration of inhaled acetylcholine (ACh) required to double pulmonary resistance (EC(200)RL) in anesthetized spontaneously breathing tracheotomized rats was calculated as an index of airway responsiveness. E(2)-treated rats were less responsive to ACh than placebo-treated rats (EC(200)RL, 9.40 +/- 1.48 vs. 1.52 +/- 0.85 mg. ml(-1), respectively). Ex vivo airway responsiveness was evaluated with the cumulative concentration-response curve (CCRC) of isolated tracheal segments. Compared with placebo, E(2) treatment significantly increased the EC(50) of ACh (p = 0.01) but did not alter the CCRC to carbachol. Removing the epithelium or treatment with physostigmine abolished the difference in EC(50) of ACh between the groups. Acetylcholinesterase (AChE) activity of homogenized whole trachea was 1.4-fold greater in the E(2)-treated group compared with placebo (p = 0.02), whereas no difference was found in homogenized epithelium-free trachea. We conclude that E(2) treatment decreases airway responsiveness to ACh in ovariectomized rats at least in part by increasing AChE activity dependent on the presence of the epithelium.

Acetylcholine↗
PubMed2001

[Acute pancreatitis--a protocol for diagnosis and treatment].

Acute pancreatitis remains a disease with high morbidity and mortality. Acute pancreatitis can be subdivided in acute interstitial pancreatitis and necrotising pancreatitis, largely compatible with clinically mild and severe pancreatitis. This diagnosis is made on the basis of patient history, physical examination, laboratory parameters, contrast CT scan and, occasionally, endoscopic retrograde cholangiopancreatography. Prognosis on admission can be established using a scoring system such as the modified Glasgow score, the Ranson score and the 'Acute physiology and chronic health evaluation'--(APACHE)-II-score. The treatment of acute pancreatitis is primarily conservative. Indications for surgical intervention are: progressive sepsis despite maximum conservative management, an established infection of (peri)pancreatic necrosis, peripancreatic abscess and perforation of stomach, small intestine or colon. The purpose of an operation is to remove necrotic tissue, achieve adequate drainage of the necrotic area or to treat a perforation. The Groningen and Utrecht University Hospitals have collaborated to develop a protocol to standardise the diagnostic approach, management, timing and choice of surgical intervention, as well as to prospectively investigate the effect of such a strategy in patients with acute pancreatitis.

Abdominal Pain↗
PubMed2001

[Reduced risk of complications associated with severe acute (necrotizing) pancreatitis by administration of antibiotics; results from a literature review].

OBJECTIVE: To determine the role of antibiotics in patients with acute pancreatitis. DESIGN: Literature review. METHOD: A Medline search for randomised clinical trials (RCTs) during the period 1990-1999 was carried out using the key words 'pancreatitis', 'acute' and 'antibiotics'. Outcome measures were pancreas-related infection, sepsis and death. RESULTS: Four RCTs were identified. Control groups were not given antibiotics. Based on the pooled data, the differences in risk in favour of the groups treated with various antibiotics were as follows: -14% (95% CI: -26(-)-1; p = 0.04) for pancreas infections, -25% (95% CI: -39(-)-12; p = 0.0002) for sepsis and -13% (95%-BI: -22(-)-3; p = 0.007) for death. CONCLUSION: Administration of antibiotics to patients with severe acute (necrotising) pancreatitis reduces the risk of serious complications.

Anti-Bacterial Agents↗
PubMed2001

The position of the alpha and beta subunits in a single chain variant of human chorionic gonadotropin affects the heterodimeric interaction of the subunits and receptor-binding epitopes.

The glycoprotein hormone family represents a class of heterodimers, which include the placental hormone human chorionic gonadotropin (CG) and the anterior pituitary hormones follitropin, lutropin, and thyrotropin. They are composed of common alpha subunit and a hormone-specific beta subunit. Based on the CG crystal structure, it was suggested that the quaternary subunit interactions are crucial for biological activity. However, recent observations using single chain glycoprotein hormone analogs, where the beta and alpha subunits are linked (NH(2)-CGbeta-alpha; CGbetaalpha orientation), implied that the heterodimeric-like quaternary configuration is not a prerequisite for receptor binding/signal transduction. To study the heterodimeric alignment of the two subunit domains in a single chain and its role in the intracellular behavior and biological action of the hormone, a single chain CG variant was constructed in which the carboxyl terminus of alpha was fused to the CGbeta amino terminus (NH(2)-alpha-CGbeta; alphaCGbeta orientation). The secretion rate of alphaCGbeta from transfected Chinese hamster ovary cells was less than that seen for CGbetaalpha. The alphaCGbeta tether was not recognized by dimer-specific monoclonal antibodies and did not bind to lutropin/CG receptor. To define if one or both subunit domains were modified in alphaCGbeta, it was co-transfected with a monomeric alpha or CGbeta gene. In each case, alphaCGbeta/alpha and alphaCGbeta/CGbeta complexes were formed indicating that CG dimer-specific epitopes were established. The alphaCGbeta/alpha complex bound to receptor indicating that the beta domain in the alphaCGbeta tether was still functional. In contrast, no significant receptor binding of alphaCGbeta/CGbeta was observed indicating a major perturbation in the alpha domain. These results suggest that although dimeric-like determinants are present in both alphaCGbeta/alpha and alphaCGbeta/CGbeta complexes, the receptor binding determinants in the alpha domain of the tether are absent. These results show that generating heterodimeric determinants do not necessarily result in a bioactive molecule. Our data also indicate that the determinants for biological activity are distinct from those associated with intracellular behavior.

Animals↗
PubMed2001

Thin-section CT of the lung: influence of 0.5-s gantry rotation and ECG triggering on image quality.

The aim of this study was to determine if ECG triggering and a shorter acquisition time of 0.5-s rotation decrease cardiac motion artifacts of thin-section CT of the lung. In 25 patients referred for thin-section thoracic CT, 1-mm thin-section slices were performed with a scanning time of 0.5 s with ECG gating, 0.5 s and 1 s during the diastolic phase of the heart at five identical anatomical levels from the aortic arch to lung basis. At each anatomical level and for each lung, cardiac motion artifacts were graded independently on a four-point scale by three readers. Patients were divided into two groups according to their heart rate. A four-way analysis of variance was used to assess differences between the three modalities. Mean cardiac motion artifacts scores were rated 1.23+/-0.02, 1.47+/-0.02, and 1.79+/-0.02, at 0.5 s with ECG gating, 0.5 s without ECG gating, and 1 s, respectively (F=139, p<0.0001). At the four anatomical levels below the aortic arch, the left lung scores were greater than the right lung score for the three modalities. For the modality 0.5 s with ECG gating no difference of scores was found between patients grouped according to their cardiac frequency. The 0.5-s gantry rotation with or without ECG gating scans reduces cardiac motion artifacts on pulmonary thin-section CT images and is mainly beneficial for the lower part of the left lung.

Adult↗
PubMed2001

The abdominal compartment syndrome: a complication with many faces.

BACKGROUND: Lately renewed attention has been given to the abdominal compartment syndrome. Despite of this there still remain a lot of controversies with regard to the pathophysiological mechanisms underlying this syndrome and the therapeutic options. METHODS: Two cases of patients with this syndrome are described and the data from animal and human trials concerning the abdominal compartment syndrome are presented and discussed. RESULTS: A variety of clinical disorders may lead to the abdominal compartment syndrome. It mainly affects the cardiovascular, pulmonary and renal organ systems. Although some clinical effects are clearly described, the exact mechanisms underlying these changes in humans are incompletely understood. It is still unclear why some patients develop abdominal compartment syndrome and others do not. The intra-abdominal pressure can easily be assessed by measuring the urine bladder pressure, which correlates well with the actual intra-abdominal pressure. All authors agree that a decompression of the abdomen by means of a laparotomy is the treatment of choice for the abdominal compartment syndrome. Which parameters should determine the indication however, remains controversial, since the correlation between clinical signs and pressure is not straightforward. CONCLUSIONS: The abdominal compartment syndrome is a well-recognised disease entity related to acutely increased abdominal pressure. Urgent laparotomy can be lifesaving in some cases. However no single threshold of abdominal pressure can be applied universally. Pending further clinical trials the best therapeutic option seems to be to decompress the abdomen surgically if the intravesical pressure is 25 mmHg or higher in patients with refractory hypotension, acute renal failure or respiratory failure due to abdominal distension.

Abdomen↗
PubMed2001

Hormonal changes in aging men: a therapeutic indication?

The rise in male life expectancy is paralleled by increased age-related clinical signs and symptoms such as muscle weakness, osteoporosis, benign prostatic hyperplasia, changes in body composition, fatigue, decreased sexual interest and activity, and increased prevalence of erectile dysfunction, all of which limit the quality of life. Many of these symptoms are similar to those of clinically well-defined hormone deficiencies, e.g. Kallman syndrome, Prader--Labhart--Willi syndrome or deficiencies due to treatment of pituitary tumors. Three male endocrine axes are characterized by age-related changes in concentrations of circulating hormones: (i) the hypothalamic--pituitary--testicular axis with lower serum levels of testosterone (T) and higher serum levels of luteinizing and follicle-stimulating hormone, (ii) the hypothalamic--pituitary--adrenal axis with its gradual decline in dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEAS), (iii) the growth hormone (GH)/insulin-like growth factor I (IGF-I) axis showing decreased hormone production concomitant with symptoms similar to those of GH-deficient adults. The beneficial effects of hormone replacement in nonelderly hormone-deficient individuals and in postmenopausal women raised hope that hormone substitution might prevent or even reverse some of the symptoms of male aging. However, this approach is hampered by the lack of individual age-related hormone reference values and reliable clinical read-out parameters. The findings so far do not support the need for widespread hormone replacement in elderly men. Larger long-term prospective studies are needed to identify clinically useful read-out parameters, and then demonstrate that hormone replacement can translate into functional parameters, thereby providing the individual benefit of treatment for aging men.

Aging↗
PubMed2001

A low-molecular-weight fraction of human seminal plasma activates adenylyl cyclase and induces caspase 3-independent apoptosis in prostatic epithelial cells by decreasing mitochondrial potential and Bcl-2/Bax ratio.

The majority of elderly men are affected by benign and malign diseases of the prostate that are governed by endocrine factors and local stromal/epithelial and luminal/epithelial interactions. Prostate epithelial cells secrete numerous factors into the seminal plasma (SMP) that are thought to be responsible for nutrition, accurate pH, and ionic environment of sperm. Our hypothesis assumes that prostatic factors responsible for optimal fertility might have retrograde influences on epithelial cell growth, differentiation, and function. SMP was analyzed for proteins and other biologically active substances by size exclusion high-performance liquid chromatography. Each fraction was investigated for its effect on cell growth and death. A low molecular mass fraction (2-4 kDa) was responsible for inducing apoptosis in proliferating prostate epithelial cells. Signal transduction was mediated by the production of cAMP; no significant changes in tyrosine phosphorylation of membrane receptors were observed. Mechanisms of apoptosis, i.e., caspase- and mitochondria-dependent pathways, were investigated in prostate epithelial cells by caspase activity assays, annexin/propidium iodide staining, changes in mitochondrial potential, p53, Par-4, Bax, and Bcl-2 protein levels. SMP induced p53- and Bcl-2-dependent apoptosis without activation of caspase-3. Obviously, SMP contains protective factors that help eliminate degenerated cells and control epithelial renewal. Age-related changes in the composition of SMP or the susceptibility of epithelial cells might, therefore, contribute to proliferative prostatic diseases

Adenylyl Cyclases↗
PubMed2001

Selected contribution: tryptase-induced PAR-2-mediated Ca(2+) signaling in human airway smooth muscle cells.

Tryptase, the major mast cell product, is considered to play an important role in airway inflammation and hyperresponsiveness. Tryptase produces different, sometimes opposite, effects on airway responsiveness (bronchoprotection and/or airway contraction). This study was designed to examine the effect of human lung tryptase and activation of protease-activated receptor (PAR)-2 by synthetic activated peptide (AP) SLIGKV-NH(2) on Ca(2+) signaling in human airway smooth muscle (HASM) cells. Immunocytochemistry revealed that PAR-2 was expressed by HASM cells. Tryptase (7.5--30 mU/ml) induced a concentration-dependent transient relative rise in cytoplasmic Ca(2+) concentration ([Ca(2+)](i)) that reached 207 +/- 32 nM (n = 10) measured by indo 1 spectrofluorometry. The protease inhibitors leupeptin or benzamidine (100 microM) abolished tryptase-induced [Ca(2+)](i) increase. Activation of PAR-2 by AP (1-100 microM) also induced a concentration-dependent transient rise in [Ca(2+)](i), whereas the reverse peptide produced no effect. There was a homologous desensitization of the [Ca(2+)](i) response on repeated stimulation with tryptase or AP. U-73122, a specific phospholipase C (PLC) antagonist, xestospongin, an inositol trisphosphate (IP(3))-receptor antagonist, or thapsigargin, a sarcoplamic Ca(2+)-ATPase inhibitor, abolished tryptase-induced [Ca(2+)](i) response, whereas Ca(2+) removal, in the additional presence of EGTA, had no effect. Calphostin C, a protein kinase C inhibitor, increased PAR-2 [Ca(2+)](i) response. Our results indicate that tryptase activates a [Ca(2+)](i) response, which appears as PAR-2 mediated in HASM cells. Signal transduction implicates the intracellular Ca(2+) store via PLC activation and thus via the IP(3) pathway. This study provides evidence that tryptase, which is increasingly recognized as an important mediator in airway inflammation and hyperresponsiveness, is also a potent direct agonist at the site of airway smooth muscle.

Acetylcholine↗
PubMed2001

Tryptase and agonists of PAR-2 induce the proliferation of human airway smooth muscle cells.

Airway remodeling with smooth muscle cell (SMC) hyperplasia is a feature of chronic asthma. We investigated the potential for tryptase, the major secretory product of human mast cells, to act as a growth factor for human airway SMCs. Because this serine protease can activate proteinase-activated receptor-2 (PAR-2), we also examined the actions of SLIGKV, a peptide agonist of PAR-2. Incubation with lung tryptase provoked a twofold increase in [(3)H]thymidine incorporation; a similar increase in cell numbers was found when we used the MTS assay. The effect was catalytic site dependent, being abolished by the protease inhibitors leupeptin and benzamidine and by heat inactivation of the enzyme. Tryptase-induced DNA synthesis was inhibited by preincubation of the cells with pertussis toxin, calphostin C, or genistein. Transduction mechanisms are thus likely to involve a pertussis toxin-sensitive G protein, protein kinase C, and tyrosine kinase. SLIGKV elicited a response on SMCs similar to that of tryptase. Tryptase could provide an important stimulus for SMC proliferation in asthmatic airways, by acting on PAR-2.

Asthma↗
PubMed2001

Prolonged moderate hyperoxia induces hyperresponsiveness and airway inflammation in newborn rats.

Bronchopulmonary dysplasia is the most common cause of chronic pulmonary disease in premature infants. Airway inflammation appears to play a major pathogenetic role together with barotrauma and oxygen toxicity. The aim of the present study was to determine the effect of a 15-d exposure to moderate hyperoxia (FiO2, 50%) on airway reactivity and inflammatory response in neonatal and adult rats. We studied in isolated tracheal rings the 1) isometric contraction to cumulative concentrations of carbachol (10(-8) to 10(-3) M); 2) epithelial, submucosal, smooth muscle, and connective tissue surface area; and 3) distribution of inflammatory cells (mastocytes, granulocytes, macrophages) by using MAb. Reactivity to carbachol was significantly increased in the hyperoxic pups, in which a 13% increase in tracheal smooth muscle surface area was observed. Type-I mast cells and macrophages (submucosa and connective tissue) and granulocytes (connective tissue) were increased in the neonatal hyperoxic group. Hyperoxia did not influence functional, morphometric, or cellular data in adult rats. In conclusion, exposure of newborn rats to moderate hyperoxia induces airway hyperresponsiveness and histologic changes similar to those reported in bronchopulmonary dysplasia. Hyperresponsiveness may be ascribed to an increase in smooth muscle related to the release of yet undetermined mediators by inflammatory cells infiltrating the airways. Lung immaturity definitely plays a role because similar alterations are not observed in adult rats.

Animals↗
PubMed2001

Seminal plasma factors induce in vitro PRL secretion in smooth muscle cells of the human prostate.

Next to the sex steroid hormone T, PRL has been shown to influence prostatic function and development. Transgenic mice overexpressing the rat PRL gene develop dramatic enlargements of the prostate gland. Proliferation and secretory activities of epithelial cells are stimulated by PRL in rodents and men. Low concentrations of human PRL (hPRL) and hPRL receptors have been observed in human prostatic epithelial cells (ECs). The aim of this study was to compare regulation of the in vitro hPRL secretion in prostatic ECs and stromal smooth muscle cells (SMCs) after stimulation with seminal plasma (SMP), containing a variety of prostatic factors. SMCs released up to 1 ng hPRL/ml (i.e., approximately 500-fold more than unstimulated SMCs and ECs). Quantification of PRL mRNA by highly sensitive quantitative RT-PCR revealed that hPRL gene expression increased 5-fold within 24 h of SMP incubation. Sex steroids (dihydrotestosterone, progesterone, 17beta-estradiol), prostaglandins (PGE-1, PGE-2), and cAMP-stimulating substances (forskolin) were not responsible for induction of hPRL. Compared with endometrial SMCs, regulation of prostatic hPRL secretion was independent of progesterone and cAMP. HPLC analysis of human SMP revealed that the common action of at least two different proteins and a low molecular cofactor is required. We concluded that prostatic ECs secrete proteins acting synergistically with low-molecular-weight cofactors to induce differentiation and hPRL release in SMCs. Age-related increases in SMC-derived hPRL might contribute to the development of benign hyperplasia of the prostate.

Adult↗