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Biomedical subjects

A F Junod

Publications and source records attributed to A F Junod.

At least 19 recordsLinked to original sources
PubMed1992

Costovertebral joint dysfunction: another misdiagnosed cause of atypical chest pain.

The diagnostic work-up of atypical chest pain frequently leads to invasive procedures. However, this painful symptomatology can sometimes be of benign origin and respond to simple therapeutic manoeuvres. A number of musculoskeletal conditions such as costovertebral joint dysfunctions should be carefully considered. We report five cases in which patient discomfort and high costs could have been avoided if awareness of these conditions had led to a correct diagnosis upon initial physical examination.

Adult↗
PubMed1992

Response of human endothelial cell antioxidant enzymes to hyperoxia.

To explore the level of regulation of the expression of the major antioxidant enzymes in response to hyperoxia, we exposed human umbilical vein endothelial cells to 95% O2 for 3 and 5 days and measured (1) the steady-state mRNA levels, (2) the activities, and (3) the immunoreactive content of CuZn and Mn superoxide dismutases (SOD), catalase (CAT), and glutathione peroxidase (GP). We found that a 3-day exposure to 95% O2 caused (1) an increase in CuZnSOD mRNA (by 41%), CAT mRNA (by 26%), and GP mRNA (by 173%); (2) an increase in CuZnSOD activity (by 30%), a decrease in CAT activity (by 37%), and an increase in GP activity (by 60%); and (3) an increase in CuZnSOD immunodetectable protein (by 26%) and a loss in CAT immunoreactive protein (by 27%). After a 5-day exposure to 95% O2, there was (1) a 93% increase in CuZnSOD mRNA, a 71% increase in CAT mRNA, and a 127% increase in GP mRNA; (2) a 56% increase in CuZnSOD activity, a 70% decrease in CAT activity, and an 89% increase in GP activity; and (3) a 35% increase in CuZnSOD immunoreactive protein and a 55% loss in CAT immunoreactive protein. There was no change in the steady-state MnSOD mRNA level after 3 days in 95% O2, but a 100% increase was observed on day 5 of oxygen exposure. MnSOD activity was unchanged in cells exposed to hyperoxia for 3 and 5 days. These data suggest that, in human umbilical vein endothelial cells, the regulation of antioxidant enzymes expression in response to O2 is complex and exerted at different levels.

Actins↗
PubMed1992

Hypoxaemia and liver cirrhosis: a new argument in favour of a "diffusion-perfusion defect".

Liver cirrhosis is sometimes associated with very severe hypoxaemia, which is thought to be the result of intrapulmonary vascular dilatations (IPVDs). These vascular abnormalities, although close to the gas exchange units, are so dilated that diffusion of oxygen molecules to their centre is impaired, causing an increase in alveolar-arterial oxygen tension difference (P(A-a)O2). On the other hand, administration of 100% oxygen provides enough driving pressure to overcome this relative diffusion defect and rules out a true intrapulmonary shunt. We report a case in which, in spite of a normal increase in arterial oxygen tension (PaO2) under 100% oxygen, exercising results in a marked impairment of oxygen exchange and a large intrapulmonary shunt. This is probably due to the increased cardiac output and preferential blood flow through these low resistance IPVDs.

Cardiac Output↗
PubMed1991

Differential protective effects of O-phenanthroline and catalase on H2O2-induced DNA damage and inhibition of protein synthesis in endothelial cells.

The respective roles of H2O2 and .OH radicals was assessed from the protective effects of catalase and the iron chelator o-phenanthroline on 1) the inhibition of protein synthesis, and 2) DNA damage and the related events (activation of the DNA repairing enzyme poly(ADP)ribose polymerase with the associated depletion of NAD and ATP stores) in cultured endothelial cells exposed to the enzyme reaction hypoxanthine-xanthine oxidase (HX-XO) or pure H2O2. Catalase added in the extracellular phase completely prevented all of these oxidant-induced changes. O-phenanthroline afforded a complete protective effect against DNA strand breakage and the associated activation of the enzyme poly(ADP)ribose polymerase. By contrast, iron chelation was only partially effective in maintaining the cellular NAD and ATP contents, as well as the protein synthetic activity. In addition, the ATP depletion following oxidant injury was much more profound than NAD depletion. These results indicate that: 1) .OH radical was most likely the ultimate O2 species responsible for DNA damage and activation of poly(ADP)ribose polymerase; 2) both H2O2 and .OH radicals were involved in the other cytotoxic effects (inhibition of protein synthesis and reduction of NAD and ATP stores); and 3) NAD and ATP depletion did not result solely from activation of poly(ADP)ribose polymerase, but other mechanisms are likely to be involved. These observations are also compatible with the existence of a compartmentalized intracellular iron pool.

Adenosine Triphosphate↗
PubMed1991

Mode of presentation and diagnosis of bacterial pneumonia in human immunodeficiency virus-infected patients.

Bacterial pneumonia (BP) has recently been reported to be more frequent in human immunodeficiency virus (HIV)-infected patients than in normal hosts. This study reviews the clinical and radiologic manifestations of BP in 132 consecutive pulmonary episodes over a 15-month period. BP was defined on a clinical basis as a pulmonary infiltrate accompanied by fever and improving in a few days with conventional antibiotics (trimethoprim-sulfamethoxazole excluded). In patients undergoing bronchoscopy (97 procedures), semiquantitative cultures and cell differentials of bronchoalveolar lavage (BAL) were performed, in addition to conventional staining and cultures for opportunistic infections. BP were frequent (45%), and the usual community-acquired pathogens were found. The radiologic manifestations of BP were often unusual, however, and 47% were indistinguishable from the typical appearance of Pneumocystis carinii pneumonia. BAL cultures had a sensitivity of 83 or 23%, depending on whether antibiotics were administered before bronchoscopy, using a cutoff value of greater than or equal to 10(4) bacteria/ml. The specificity of BAL culture was of 80.5% if patients with P. carinii pneumonia were taken as a control group. We conclude that BP is frequently encountered in HIV-infected patients. The clinical and radiologic presentation of BP may be indistinguishable from that of opportunistic infections. Semiquantitative cultures of BAL appear a valuable diagnostic tool to avoid unnecessary invasive diagnostic procedures or treatments.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Differential expression of hsp70 stress proteins in human endothelial cells exposed to heat shock and hydrogen peroxide.

The potential role of oxidative stress conditions in the induction of heat shock proteins was studied in human umbilical vein endothelial cells. We compared the effects of temperature (43 to 45 degrees C), exposure to hydrogen peroxide (H2O2) and oxygen metabolites generated by the enzyme system hypoxanthine-xanthine oxidase (O2- plus H2O2), as well as exposure to 95% O2, on the expression of the major 70-kD heat shock proteins (hsp70). Northern blot analysis indicated that: (1) heat shock induced a rapid and marked increase in hsp70 mRNA levels that reached a maximum during recovery from a 30-min exposure to 45 degrees C; (2) treatment with a 5-mM H2O2 bolus or 50 mU/ml xanthine oxidase also increased hsp70 mRNA levels but to a lesser extent than heat shock (about 10 and 25 times less, respectively); (3) no change was detected after a 5-day exposure to 95% O2. Nuclear run on transcription data and kinetics of mRNA decay in the presence of actinomycin D indicated that the observed increase in hsp70 mRNA levels in both heat-shocked and H2O2-treated cells was mainly due to a transcriptional induction. The kinetics of hsp70 synthesis correlated with the accumulation of hsp70 mRNA. Two-dimensional gel electrophoresis and immunologic analysis of these heat shock proteins revealed a series of at least five distinct hsp70 isoforms induced in heat-shocked cells, whereas only a specific subset of these proteins, mainly one acidic isoform, was induced in very low amounts in response to H2O2 treatment. These results clearly indicate that the endothelial cell responses to oxidative stress and heat shock differ in both qualitative and quantitative terms in respect to hsp70 induction. They also suggest that the intensity of this response to oxidative stress conditions may vary depending on the nature of the oxidative challenge.

Blotting, Western↗
PubMed1991

[Episodic laryngeal dyskinesia: a functional cause of stridor].

We present five cases of episodic laryngeal dyskinesia. This term describes an entity associating acute dyspnea with inspiratory and/or expiratory stridor, sometimes ending in acute respiratory distress. The origin of this trouble comes from paradoxal contraction of the vocal cords, which is reversible and recurrent. The clinical presentation presents as a differential diagnosis for serious disorders such as bronchial asthma, laryngeal oedema, or stenosing lesions of the upper airways. The definitive diagnosis is made by excluding organic pathology, by visualising laryngeal spasm and by the inspection of flow volume curve. A comparison of all the published papers since 1974 reveals the benign nature of this "noisy" disorder and to bring out the diagnostic criteria thus avoiding too aggressive an approach in these patients.

Adolescent↗
PubMed1990

[Prevention and screening: which decisions should be made?].

The definition of the various types of prevention, of screening and of case-finding are recalled, and the particular requirements of screening within an apparently normal population are analyzed. The characteristics of a screening test are reviewed, with emphasis on the prevalence of the disease, which, together with the specificity of the test, conditions the positive predictive value. The consequences of the false positive and false negative are briefly detailed and the benefit/cost ratio is defined. Interpretation of the results is rendered difficult by the existence of certain biases including the lead-time bias and the length-time bias. These complex elements should be taken into consideration in a physician's regular case-finding in his patients.

Epidemiologic Methods↗
PubMed1990

[Is pulmonary interstitial pathology an entity?].

Pulmonary interstitial diseases cannot be defined as an entity because of the existence of multiple pathogenic factors, and of various radiological expressions, as well as of the involvement of different types of inflammatory cells. Moreover, several hypotheses can be considered to explain the fibroblastic hyperplasia often present in this condition. It could be the result of an excess of secretion of growth factors, of an enhanced sensitivity of the target cells to these factors, of a decrease of factors inhibiting fibroblast replication, or of a relative deficiency of monokine antagonists. A similar analysis could be applied to chemotactic factors for fibroblasts as well as for those stimulating collagen production.

Fibroblasts↗
PubMed1990

Characterization of a specific 20- to 25-kD interleukin-1 inhibitor from cultured human lung macrophages.

Alveolar macrophages have the ability to downregulate immune processes in vitro. We have recently suggested the presence of interleukin-1 (IL-1) inhibitors in the supernatants of human bronchoalveolar lavage cells from patients with idiopathic pulmonary fibrosis or sarcoidosis. In the present study, we further analyze the cellular origin and the biologic properties of a 20- to 25-kD IL-1 inhibitor spontaneously produced by cultured human alveolar macrophages (AM). The inhibitor blocks IL-1-induced prostaglandin E2 production by human fibroblasts and the IL-1-related increase of phytohemagglutinin-induced murine thymocyte proliferation. After rigorous IL-1 alpha and IL-1 beta depletion, supernatants of lung macrophages specifically block the binding of IL-1 to its receptor on the murine thymoma cell line EL4-6.1 in a dose-dependent manner. These results indicate that AM from both normal donors and patients produce a specific IL-1 inhibitor that may be of importance in protecting the alveolar environment from the deleterious effects of excessive IL-1 production.

Biological Assay↗
PubMed1990

Fibroblast-alveolar cell interactions in sarcoidosis and idiopathic pulmonary fibrosis: evidence for stimulatory and inhibitory cytokine production by alveolar cells.

To better understand how the activity of inflammatory cells collected by bronchoalveolar lavage (BAL) could affect the outcome of granulomatous and fibrotic pulmonary diseases, we studied secretory products and messenger ribonucleic acid (mRNA) expression for certain cytokines of BAL cells in 10 controls, 14 patients with interstitial pulmonary fibrosis (IPF) and 22 patients with sarcoidosis. We assayed the activity of 48 h conditioned media for: 1) their biological action on fibroblast proliferation and prostaglandin E2 (PGE2), collagenase and collagen production by fibroblasts; 2) TNF alpha levels by bioassay and radioimmunoassay; 3) interleukin 1 (IL-1) alpha and beta and beta levels by solid phase enzyme immunoassay (EIA); 4) tumor necrosis factor (TNF) and IL-1 inhibitory activity. We also measured, in freshly isolated BAL cells: 1) mRNA levels for IL-1 alpha and beta and TNF alpha; 2) cell-associated IL-1 alpha and beta by EIA. The only difference found in the assessment of the biological activity of BAL cells conditioned medium was an increase in fibroblast proliferation in sarcoidosis vs IPF patients. The IL-1 alpha and beta, and TNF alpha contents of conditioned media were similar in the three groups. Inhibitory activity against IL-1 and TNF alpha was found in a few patients. Further analysis revealed two peaks of inhibitory activity against IL-1 (20-25 kD and 35-40 kD), as well as a distinct TNF alpha inhibitory activity which could be retained on a TNF alpha-binding affinity column. No mRNA expression for TNF alpha was found in freshly isolated BAL cells, whereas very variable levels of IL-1 alpha and beta mRNA levels were detected in the three groups. Because of these variable results of differences in functional state between freshly isolated and cultured BAL cells, and of the presence of inhibitory substances against IL-1 and TNF alpha, it is unlikely that the development of fibrosis could be ascribed to a single disorder or abnormality.

Adult↗
PubMed1990

[Isolated alveolar hypoventilation as a tubercular sequellae].

Whilst the sequelae of extensive tuberculous infections generally manifest as an overall respiratory failure, characterised by a rise in the alveolar arterial gradient for oxygen and often CO2 retention, we report some observations on six patients with significant pleural and parenchymal tuberculosis; these patients presented with a restrictive syndrome associated with an apparently isolated alveolar hypoventilation. In four of these patients an effort test showed that there was adequate adaptation to alveolar ventilation on effort. In one patient measurement of PO.1 in a resting state and then during the course of a test of CO2 responsiveness revealed an absence of any response to CO2. On the basis of these results, we propose that in certain subjects suffering from significant sequelae of tuberculous disease the major functional abnormalities can be expressed as alveolar hypoventilation. This latter is not necessarily followed by a mechanical overload leading to an eventual fatigue of respiratory muscles but rather to a disorder of the regulation of ventilation. The basic mechanism of such an anomaly remains undetermined.

Aged↗
PubMed1989

[The rational use of various tests for the diagnosis of pulmonary embolism].

The patient's history, physical examination, chest X-ray, electrocardiogram and blood gas analysis cannot provide a firm diagnosis of pulmonary embolism, but they can help to assess its clinical or a priori probability. Lung perfusion scan, associated with ventilation scan or not, can modulate the probability of pulmonary embolism (post-test or a posteriori) as a function of the scan result (high probability, low probability, or indeterminate result). To define the proper indication for pulmonary angiography, it is necessary to examine all the factors related to the nature of the test, the risk, and the data related to pulmonary embolism (outcome, efficacy and side effects of treatment). Decision analysis provides an opportunity to integrate all these factors, and may help in the diagnosis of pulmonary embolism by establishing the indication for pulmonary angiography, depending on clinical probability and the result of the lung scan.

Angiography↗
PubMed1989

Differential effects of hyperoxia and hydrogen peroxide on DNA damage, polyadenosine diphosphate-ribose polymerase activity, and nicotinamide adenine dinucleotide and adenosine triphosphate contents in cultured endothelial cells and fibroblasts.

The effects of oxidative stress on DNA damage and associated reactions, increased polyadenosine diphosphate-ribose polymerase (PARP) activity and decreased nicotinamide adenine dinucleotide (NAD) and adenosine triphosphate (ATP) contents, have been tested in primary cultures of porcine aortic endothelial cells. The cells were treated with 50-500 microM H2O2 for 20 min or 100 microM paraquat for 3 days or were exposed to 95% O2 for 2 and 5 days. The administration of 250-500 microM H2O2 resulted in a marked increase in PARP activity and a profound depletion of ATP and NAD. Although hyperoxia had no effect on PARP activity and reduced only slightly the ATP and NAD stores, it markedly reduced the ability of endothelial cells to increase PARP activity upon exposure to DNase. Paraquat had a similar effect. Human dermal fibroblasts were also exposed to 50-500 microM H2O2 for 20 min or 95% O2 for 5 days. Their response to H2O2 differed from that of endothelial cells by their ability to maintain the ATP content at a normal level. Fibroblasts were also insensitive to the effect of hyperoxia. These results suggest that the oxidant-related DNA damage is a function of the type of oxidative stress used and may be cell-specific.

Adenosine Triphosphate↗
PubMed1989

Oxygen free radicals and lungs.

Some of the metabolites resulting from the monovalent reduction of O2, superoxide anion and hydroxyl radical, are O2, radicals, whereas H2O2, which is not a radical since having no unpaired electron, is also an active O2 intermediate. These O2 metabolites are formed intracellularly as a result of normal metabolism. Their production can increase following exposure to high O2 concentration, radiations or certain drugs. An increased amount of extracellular O2 metabolites occurs after activation of certain inflammatory cells or during the course of the hypoxanthine-xanthine oxidase reaction. To counteract this oxidative stress, antioxidant defenses exist, whether enzymatic (superoxide dismutase, glutathione peroxidase, catalase, etc.) or nonenzymatic (GSH, vitamin E and C, etc.). Oxidative injury can result from an imbalance between oxidative stress and the defense mechanisms. The main targets are protein, DNA and lipids. The cellular response of the lung is stereotyped and involves cell injury (especially endothelial cells and type I pneumocytes), inflammatory reaction and repair processes.

Free Radicals↗
PubMed1989

Hypoxanthine-xanthine oxidase-related defect in polypeptide chain initiation by endothelium.

After exposure to O2 intermediates generated by the hypoxanthine-xanthine oxidase system (HX-XO), the rate of [3H]phenylalanine incorporation into total proteins in cultured endothelial cells was markedly reduced. This reduction, which was prevented by catalase, could not be explained by 1) changes in amino acid pools, 2) increased rate of degradation of newly synthesized proteins, 3) impaired poly(A)+ RNA synthesis and efficiency, 4) decreased rate of amino acylation. On the other hand, the increase in the monoribosome-to-polyribosome ratio suggested that translation was affected at the level of chain initiation. Further analysis indicated that 40S initiation complex formation was normal, whereas the assembly of 80S initiation complex was inhibited. Results from reconstitution experiments showed that both normal and treated ribosomes could support normal protein synthesis in the presence of normal initiation factors (IFs). In contrast, IFs from HX-XO lysates did not support normal protein synthesis with ribosomes from either source. Thus, the effect of XO treatment on protein synthesis appears to be an initiation defect related to decreased IF activity and/or availability.

Adenosine Triphosphate↗
PubMed1988

Effects of oleic acid-, alpha-naphthylthiourea-, and phorbol myristate acetate-induced microvascular damage on indexes of pulmonary endothelial function in anesthetized dogs.

To study the value of indexes of endothelial cell function in experimentally induced pulmonary microvascular injury, lung damage was produced in anesthetized dogs by intravenous injection of oleic acid (OA; n = 6), alpha-naphthylthiourea (ANTU; n = 5), or phorbol myristate acetate (PMA; n = 6). Angiotensin-converting enzyme (ACE) activity in serum and simultaneous measurements of serotonin (SER) and propranolol (PROP) pulmonary extraction along with several physiologic parameters were determined and compared with those obtained in a control group (n = 5) before and then at 2-h intervals for 8 h after administration of the toxic agent. ACE activity in serum showed a sustained and significant increase in the PMA and OA groups throughout the whole study period, whereas it decreased significantly at 4 h in the ANTU group. SER pulmonary uptake decreased significantly, but slightly, only in the PMA group at 8 h (-5%). At 6 and 8 h respectively, PROP extraction dropped significantly in the PMA (-11 and -13%) and OA (-13 and -19%) groups. This decrease in PROP extraction was likely to result from physiologic changes due to the development of pulmonary edema as suggested by the correlation between the changes in amine uptake and those affecting pulmonary artery pressure and total static respiratory compliance. The lack of effects on SER uptake by the lungs under these experimental conditions indicate that dissociation exists between metabolic dysfunction of pulmonary endothelial cells and fluid leakage.

Anesthesia↗