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Biomedical subjects

M Allam

Publications and source records attributed to M Allam.

11 recordsLinked to original sources

Differential expression of PDGF A- and B-chain genes and production of AA and AB dimers by activated human blood monocytes.

Platelet-derived growth factor (PDGF) is composed of two chains (A and B) bound by disulfide bridges. Blood monocytes (BM) express the c-sis proto-oncogene, the gene coding for PDGF B-chain, and release PDGF. To evaluate PDGF release and A- and B-chain gene expression by BM, normal BM were cultured with LPS and specific transcripts for PDGF A- and B-chain genes were detected by Northern analysis and PDGF dimers by specific Elisas. Normal BM did not spontaneously express either A- or B-chain gene while, when activated, PDGF B-chain expression was precocious (maximum at 1 h) and decreased over 24 h; PDGF A-chain transcripts were present after 4 h and progressively increased over 24 h. Furthermore, activated BM released more AB dimers than AA dimers and almost no BB dimers. This observation confirms the concept of PDGF A- and B-chain separate gene regulation, and defines the specific molecular pattern of PDGF released by activated BM.

Blotting, Northern

Differential migratory response of U-2 OS osteosarcoma cell to the various forms of platelet-derived growth factor.

U-2 OS osteosarcoma cells are mesenchymal-derived transformed cells spontaneously expressing both platelet-derived growth factor (PDGF) A- and B-chain genes, and releasing PDGF AA dimers in culture. Using modified Boyden chemotactic chambers, platelet-purified PDGF was shown to be a chemoattractant for U-2 OS cells. More specifically, U-2 OS cells migrated in the presence of PDGF AB and BB dimers but not in the presence of PDGF AA dimers. This pattern of response was similar to that observed with human fibroblasts and this similarity is consistent with the fact that U-2 OS cells express PDGF receptor alpha- and beta-subunits in a similar fashion to human fibroblasts.

Chemotaxis

Effect of acute and chronic moderate hypoxia on the kinetics of lidocaine and its metabolites and on regional blood flow.

The effect of acute and chronic hypoxia on the disposition of lidocaine and its metabolites, and on regional blood flow has been examined in conscious beagles (n = 5). Each dog received an infusion of lidocaine for 5 h under three experimental conditions: (1) breathing air; (2) following acute exposure to a FIO2 of 8% and a FICO2 of 3.5% to generate a PaO2 of 45 mmHg without hypocapnia; and (3) after 6 days of hypoxemia. Multiple blood samples were drawn to assess the kinetics of lidocaine and its metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX). Three hours after the end of the infusion of lidocaine, the dogs received radioactive microspheres to estimate hepatic, renal and brain blood flow. Neither acute nor chronic moderate hypoxia affected the kinetics of lidocaine, the parent compound. However, both experimental conditions increased plasma concentrations of MEGX and GX and increased the ratio of the area under their plasma concentration curves to the dose of lidocaine received. Acute moderate hypoxia increased brain blood flow, although it did not affect liver or renal perfusion. Chronic moderate hypoxia did not significantly change the blood flow to any of the organs studied. It was concluded that acute and chronic moderate hypoxia decreases the rate of elimination of both active metabolites of lidocaine without modifying the perfusion to the organs responsible for their elimination.

Animals

Presence of platelet-derived growth factor in normal and fibrotic lung is specifically associated with interstitial macrophages, while both interstitial macrophages and alveolar epithelial cells express the c-sis proto-oncogene.

Normal lung structure is maintained by the presence of mesenchymal cells and their extracellular matrix products. The slow normal turnover of these cells is disrupted in fibrotic disorders, resulting in the in situ accumulation of mesenchymal cells and their extracellular matrix leading to a progressive alveolar wall thickening. Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic disorder of the lung characterized by a diffuse interstitial and intra-alveolar inflammation dominated by macrophages and polymorphonuclear neutrophils. Evaluation of alveolar macrophages (AM) obtained by bronchoalveolar lavage has previously shown that AM from normal individuals spontaneously release small amounts of platelet-derived growth factor (PDGF), a chemotactic and growth factor for mesenchymal cells, whereas AM from IPF patients spontaneously release increased amounts of biologically active PDGF, suggesting its involvement in mesenchymal cell accumulation. However, other cells such as endothelial cells and vascular smooth muscle cells can also release PDGF in vitro. In order to specify PDGF location in lung parenchyma, open lung biopsies from normal individuals and IPF patients were examined by immunohistochemistry using an anti-PDGF antibody and by in situ hybridization using PDGF A-chain and B-chain gene probes. In normal as well as in fibrotic lung, PDGF was only present in relation with interstitial macrophages but not with any other inflammatory cells or mesenchymal cells. Furthermore, the percentage of PDGF-positive macrophages in IPF was 3-fold increased in comparison to normal lung. In addition, the percentage of PDGF-positive macrophages was the same in fibrotic and nonfibrotic areas of IPF lungs.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Epidural technique.

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Anesthesia, Epidural

The inotropic effect of digoxin on an isolated rat heart in hypercapnia and (or) hypoxia.

The explanation for the increased frequency of troubles with digoxin therapy in patients with chronic pulmonary diseases is debated. The reported effects of hypoxia in vivo on myocardial levels of digoxin are contradictory, and there have been few studies on the effects of hypercapnia. In the past, it has been shown in rat myocardial tissue at rest in vitro that hypoxia decreased and hypercapnic acidosis increased the digoxin uptake. We performed a new study in vitro in an isolated beating rat heart perfused at constant flow (37 degrees C) and stimulated at a constant frequency (6 Hz). The performances were recorded with an intraventricular balloon equipped with a tip-manometer catheter. The action of digoxin was studied by recording systolic pressure (PS) and diastolic pressure (PD), the left ventricular developed pressure (LVDP = PS - PD), the (dP/dt)max, and the ratio (dP/dt)max/PS. First, the heart was perfused for 30 min with a modified Tyrode's solution perfusate aerated with carbogen (pH = 7.40; PCO2 = 37 mmHg; PO2 = 530 mmHg) (1 mmHg = 133.32 Pa). Various parameters of contractions were recorded (initial control values). Then the heart was perfused for 15 min with Tyrode's solution aerated either with a hypoxic gas mixture (pH = 7.41; PCO2 = 36 mmHg; PO2 = 122 mmHg), a hypercapnic gas mixture (pH = 7.08; PCO2 75 mmHg; PO2 = 485 mmHg), or a hypoxic-hypercapnic gas mixture (pH = 7.09; PCO2 = 73 mmHg; PO2 = 124 mmHg). Control hearts were continuously perfused with Tyrode's solution aerated with carbogen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Cardiac derived neutrophil chemotactic factors; preliminary biochemical characterization.

The purpose of this study is to investigate whether isolated hearts perfused with cardioplegic solution release inflammatory mediators such as neutrophil chemotactic factors (NCF). Three conditions were tested, including: (1) perfusion of rabbit hearts with crystalloid cardioplegic solution (4 degree C) saturated with air (95% oxygen) and containing dextrose (i.e. complete system), (2) perfusion of rabbit hearts with non-oxygenated cardioplegic solution, containing dextrose (i.e. minus oxygen system), and (3) perfusion of hearts with cold cardioplegic solution saturated with air in the absence of dextrose (i.e. minus dextrose system). At various time intervals (5 min, 1, 2, 3 and 4 h) samples of circulated perfusate were removed and assayed for the presence of NCF using modified Boyden chambers. Rabbit peritoneal neutrophils were the indicator cells. The standard chemoattractant, f-Met-Leu-Phe (f-MLP) was the positive control. High levels of neutrophil chemotactic activity were detected in perfusate of all above described hearts perfused for 4 h (i.e. 194 +/- 22% of f-MLP control--complete system, 126 +/- 13%--minus oxygen and 136 +/- 10%-minus dextrose). Histological evaluation of these hearts showed evidence of global ischemia. We also detected significant levels of NCF in effluent of hearts perfused for 5 min, 1, 2 and 3 h. Similar to perfused hearts, isolated rabbit hearts incubated for 4 h with non-oxygenated cardioplegic solution (in presence and absence of dextrose) released high levels of NCF (132 +/- 18%-intact heart; and 100 +/- 6% myocardial segments). Standard checkerboard analysis revealed that the observed activity released from these hearts is chemotactic.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Effects of hypoxia and hypercapnia on atrial natriuretic factor and plasma renin activity in conscious dogs.

1. The aim of the present study was to assess the effects of hypercapnia or hypoxia on plasma concentrations of atrial natriuretic factor (ANF) in conscious unrestrained dogs. 2. For this purpose, chronically instrumented dogs were exposed in a random order to either room air, or to an atmosphere containing 21% O2/10% CO2/69% N2 to produce hypercapnia, or 10% O2/3% CO2/87% N2 to produce hypoxia without respiratory alkalosis. 3. Plasma concentrations of ANF did not change significantly during hypoxia. 4. In contrast, during hypercapnia, plasma concentrations of ANF increased by more than 100% and returned to baseline at the end of hypercapnia. 5. Hypercapnia, but not hypoxia, induced an increase in left atrial and central venous pressures. 6. We conclude that hypercapnia increases plasma ANF concentration, and that this increase may be secondary to an increase of the left and right atrial pressures. These phenomena may explain the increase in diuresis and natriuresis which has been described during hypercapnia.

Animals

Effect of the standardized Ginseng Extract G115 on the metabolism and electrical activity of the rabbit's brain.

The objective of this original investigation was to study the effect of the standardized Ginseng Extract G115 on the metabolic activity and ECoG of the rabbit's brain. The results showed significant increase of the glucose uptake with simultaneous significant reduction of the lactate, pyruvate and lactate/pyruvate ratio. These findings indicate shift of glucose utilization by the drug from anaerobic to the more economical pathway. G115 was also shown to produce a desynchronizing effect on the electrocorticogram (ECoG) which correlated well with the biochemical findings.

Animals

Psychometric assessment of the therapeutic efficiency of antidepressant agents.

A clinical trial of four weeks duration was conducted involving a total of thirty depressed patients, of both sexes, aged between twenty and thirty-four years. The total number of patients was divided into three groups of ten patients each. One group received amitriptyline, the second group was administered noxiptyline and the third group was given dibenzepine. All drugs were administered orally. Patients were submitted to psychometric testing before and after drug administration. The tests used included the 'Hamilton Rating Scale for depression', the 'Hildreth Feeling Scale' and the 'D Scale' and the 'Trail Making Test' for the evaluation of psychomotor retardation. It was concluded that the Hamilton Rating Scale was the most relatively sensitive test utilized in assessing the depressive state and its improvement. Amitriptyline was found to be mostly anxiolytic; noxiptyline controlled both depression and anxiety to approximately the same extent; and dibenzepine was found to be a mood-elevating drug with an energizing action.

Adult