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Biomedical subjects

F Moreau

Publications and source records attributed to F Moreau.

At least 19 recordsLinked to original sources

The E5 gene from human papillomavirus type 16 is an oncogene which enhances growth factor-mediated signal transduction to the nucleus.

Although human papillomavirus type 16 (HPV-16) is believed to be a major etiological agent in the development of cervical cancer, the biological function of several of its early genes remains to be established. In the present study, we have defined some of the biological properties of the E5 gene from HPV-16. Expression of the HPV-16 E5 gene in 3T3-A31 cells induced transformation to anchorage-independent growth (colony formation in soft agar). Addition of epidermal growth factor (EGF) to the soft-agar medium caused the E5-expressing cells to form larger colonies than those formed in the absence of EGF. Parental 3T3-A31 cells did not form colonies in soft agar either in the presence or in the absence of EGF. Analysis of clones expressing high levels of E5 mRNA revealed that these cells also expressed higher levels of c-fos mRNA in response to serum, EGF and platelet-derived growth factor (PDGF) than did the parental 3T3-A31 cells. Cells expressing the E5 gene were also capable of accelerated growth in low serum and were more tumorigenic in nude mice than were control cells. We conclude that the E5 gene from HPV-16 is an oncogene which transforms cells in part through enhancing signal transduction from growth factors to the nucleus.

3T3 Cells

[Experimental study of fulguration on a healthy ventricle. I. Acute lesions].

The effect of fulguration shocks applied to the healthy ventricular myocardium in 6 pigs weighing between 63 and 100 kg showed that for shocks with the same energy level as those used in clinical practice, the immediate effects of fulguration result in a hemorrhagic zone with a diameter of up to 15 mm. Histopathological examination revealed tearing of the cardiomyocytes which is probably related to barotraumatic phenomena. Deflagrating shocks of 90 Joules, with a short development time (non-self-inductive circuit) can lead to perforation of the myocardium in both the right and left ventricles. In this animal model, arrhythmia was rare and did not lead to sudden death in any case. No vascular damage was observed.

Acute Disease

[Experimental study of fulguration of healthy ventricle. II. Chronic lesions].

The effect of fulguration shocks was studied using healthy ventricular myocardium of 12 pigs weighing between 63 and 100 kg. With shocks of equal energy to those used clinically, lesions seen 24 hours after the session in two pigs showed the formation of loose fibrosis and of marked cellular infiltration as well as zones of hypercontraction with calcium precipitation. The size of chronic lesions seen during periods ranging from one week to 2 months was studied in 4 pigs. Transmural plaques with a diameter of 1.5 to 2 cm were seen in the right ventricle. For the same energy levels of 240 Joules delivered to left ventricular tissue, lesions were of the same size but were never transmural. Under certain conditions, lesions were disposed in the direction of the neutral electrode.

Acute Disease

Expression of the human papillomavirus E7 oncogene during cell transformation is sufficient to induce susceptibility to lysis by activated macrophages.

Human papillomaviruses (HPV), and in particular HPV type 16, are etiologic agents in the development of cervical cancer, which is the second most common form of cancer in women worldwide. Mammalian cells are susceptible to transformation in vitro by the E6 and E7 oncogenes derived from the HPV-16 genome. NIH-3T3 cells transfected with the HPV-16 E7 oncogene were found to exhibit cytolytic susceptibility to murine-activated macrophages. In comparison, E6 oncogene-expressing cells were not susceptible to lysis by activated macrophages. The E7 oncoprotein is multifunctional, being capable of complexing with the retinoblastoma tumor suppressor gene (anti-oncogene) product, stimulating DNA synthesis, and causing cell transformation in vitro. Macrophage killing assays performed on cell lines expressing E7 mutants revealed that the ability to complex the retinoblastoma tumor suppressor gene product and stimulate DNA synthesis did not induce susceptibility to activated macrophages, whereas the ability of E7 to cause transformation was required to induce susceptibility to activated macrophages. These data suggest that cell transformation is a more important prerequisite for inducing susceptibility to activated macrophages than is the loss of tumor suppressor gene function. This study also provides an initial link between HPV-16 oncogene expression and the ability of activated macrophages to selectively recognize and destroy HPV-16-associated neoplastic cells.

Amino Acid Sequence

Variations in energization parameters and proton conductance induced by cold adaptation and essential fatty acid deficiency in mitochondria of brown adipose tissue in the rat.

Male weanling Long-Evans rats were fed on a low-fat semipurified diet (control diet, 2% sunflower oil; essential fatty acid (EFA) deficient diet, 2% hydrogenated coconut oil) for 9 weeks. In order to modulate need for non-shivering thermogenesis, groups of rats on each diet were exposed at 28 degrees C (thermoneutrality) and at 5 degrees C (cold acclimation) for the last 5 weeks. In brown adipose tissue (BAT) mitochondria, several parameters of mitochondrial energization, protonmotive force (delta p) and its components delta pH and membrane potential, delta psi, were investigated. Simultaneous measurement of oxygen consumption and delta psi (the main component of delta p) was performed by varying alpha-glycerophosphate concentration and the force/flux relationship of the mitochondria was established by comparison of proton conductance, CmH+, over the whole range of protonmotive force. delta p. In the absence of GDP, at 28 degrees C, EFA deficiency induced a marked increase in CmH+. Cold acclimation led to comparable enhanced CmH+ in control and EFA-deficient mitochondria. In the presence of GDP which binds and inhibits the BAT 32 kDa uncoupling protein, CmH+ was the same in 28 degrees C and 5 degrees C control mitochondria, but EFA deficiency led to an enhanced GDP independent CmH+ at 28 degrees C and to a lesser extent at 5 degrees C. These results are discussed with reference to substantial changes in mitochondrial lipid composition induced by the deficiency.

Adipose Tissue, Brown

Stable expression of functional mitochondrial uncoupling protein in Chinese hamster ovary cells.

The mitochondrial uncoupling protein (UCP) is a membranous proton carrier exclusively synthesized in brown adipocytes. The cDNA for the rat UCP was placed in an expression vector and transfected into mammalian cells. Its expression was tested in transiently transfected CHO cells. In these cells the UCP was detected in mitochondria by using antibodies. Permanent expression of the UCP was achieved in stable transformed CHO cell lines. In these cells the UCP was characterized in mitochondrial membranes, by using antibodies and hydroxyapatite purification. The protein expressed in CHO cells displayed the functional characteristics of brown adipocyte UCP. It induced the uncoupling of respiration in isolated CHO mitochondria. The membrane potential of transformed mitochondria was also significantly lowered, as a result of the proton translocating activity of the UCP. GDP is known to inhibit the proton pathway in brown fat mitochondria. Addition of GDP to CHO mitochondria containing UCP resulted in a recoupling of respiration and an increase in membrane potential. Thus we conclude that functional UCP is expressed in CHO cells and that the insertion of the UCP alone in any mitochondria is sufficient to induce the uncoupling of respiration. This approach should allow studies on the structure-function relationship of the UCP and of several other related mitochondrial carriers.

Adipose Tissue, Brown

[Echocardiography in anorexia nervosa].

The echocardiographic parameters of 10 patients with anorexia nervosa were studied at the time of admission and compared with those of 10 matched controls. There was a decrease of ventricular volumes and of the calculated left ventricular mass, but the haemodynamic values at rest showed a normal "pump function". The left ventricular mass correlated with the body mass, which indicates that the heart of anorectic patients is also involved by malnutrition. Two patients had asymptomatic mitral valve prolapse. These results are in agreement with the few published studies which report deep cardiac alterations with decrease of heart cavities volumes and reduction of wall thickness and myocardial mass. This results in altered exercise performance, despite a satisfactory haemodynamic status at rest. The high frequency of mitral valve prolapse due to disproportion between ventricle and valve must be noted.

Adolescent

The principal artery of the psoas major muscle.

The psoas major m. has a complex arterial supply, derived from the lumbar, iliolumbar, obturator, external iliac and common femoral a. The branches arising from the external iliac a., though quite often multiple and slender, are represented in 75% of cases by a single large-caliber vessel. This principal artery of the psoas m. is probably responsible for the curves of the external iliac a. in the aged and also in certain competitive athletes.

Age Factors

[Crush injury of the lower limbs. Use of anti-shock trousers].

A case of lower limb crush injury is reported. A 16 year old female sustained severe soft tissue, muscle, skeletal and vascular lesions during a road traffic accident. She rapidly presented with severe haemorrhagic shock due to a popliteal arterial injury. At the scene, massive vascular loading by emergency physicians using both colloids and group O negative packed red cells was not enough to improve the haemodynamic state, even though there was adequate control of the bleeding artery. The pneumatic antishock trousers were therefore used despite the severe injuries to the legs, with rapid improvement of the haemodynamic parameters. By using bilateral femoral nerve blocks, the limb fractures were reduced rapidly; this decreased ischaemic time and allowed correct placement of the garment. Although the left leg was amputated above the knee, the postoperative course was uneventful. The authors insist on the important part such early management at the scene plays in preventing acute post-traumatic renal failure.

Acute Kidney Injury

Relationship of free intracellular calcium to the cytolytic activity of Entamoeba histolytica.

Entamoeba histolytica adherence and destruction of host cells is required for in vivo pathogenicity; amebic in vitro adherence is mediated by a galactose- or N-acetyl-D-galactosamine-inhibitable surface lectin (Gal/GalNAc adherence lectin). Free intracellular Ca2+ concentration [( Ca2+]i) was measured in living amebae and target cells during amebic cytolysis of Chinese hamster ovary (CHO) cells and human polymorphonuclear neutrophils by utilizing the Ca2+ probe Fura-2 and computer-enhanced digitized microscopy. Motile E. histolytica trophozoites had oscillatory increases in [Ca2+]i in head or tail regions; however, there was no increase in regional or total amebic [Ca2+]i upon contact with a target CHO cell. Target CHO cells and polymorphonuclear neutrophils demonstrated marked irreversible increases in [Ca2+]i within 30 to 300 s following contact by an ameba (P less than 0.01); increased [Ca2+]i preceded the occurrence of nonspecific surface membrane permeability and death of the target cell. Target CHO cells contiguous on a monolayer to a cell contacted by an ameba experienced a rapid but reversible rise in [Ca2+]i (P less than 0.01) and were not killed. Galactose (40 mg/ml) totally abrogated the rise in target CHO cell [Ca2+]i that followed contact by amebae (P less than 0.01); immunoaffinity-purified amebic Gal/GalNAc adherence lectin (0.25 micrograms/ml) induced a rapid and reversible rise in CHO cell [Ca2+]i (P less than 0.01) which was inhibited by galactose. Amebic [Ca2+]i was not elevated following parasite adherence to target cells; a rapid and substantial rise in target cell [Ca2+]i occurred which was mediated, at least in part, by the Gal/GalNAc adherence lectin of the parasite and led to the death of target cells.

Adhesiveness

Entamoeba histolytica: chemoattractant activity for gerbil neutrophils in vivo and in vitro.

The kinetics of the host's cellular response in the peritoneal cavity of gerbils toward axenic pathogenic and nonpathogenic Entamoeba histolytica strains were examined. Amebae contained in diffusion chambers or free in the peritoneum elicited a neutrophilic response accompanied by decreased levels of macrophages and lymphocytes. Pathogenic amebae (IP:0682:1 strain) elicited a neutrophilic response greater than the nonpathogenic DKB and "entamoeba-like" Laredo amebae. The neutrophil eliciting factor was found in high levels in disrupted freeze-thawed amebae (53% elicited neutrophils vs 8% for control), glutaraldehyde fixed amebae (45%) and amebic membranes (65%), and low levels in conditioned amebic medium (15%) and the supernatant fraction of amebae (16%). The factor was heat stable to high temperature (100 C for 30 min) and at various pH (6 to 9). The neutrophil eliciting factor in amebic membranes was lowered following pretreatment for 30 min with 1% immune and nonimmune gerbil or human sera (34-48% lowered neutrophil response vs control), acidic pH (less than 3, 69%), proteolytic digestion [trypsin (68%) and alpha-chymotrypsin (72%), 100 micrograms/ml], and 2% Triton X-100 (75%). Peritoneal neutrophils isolated following stimulation with amebic membranes or thioglycollate medium demonstrated higher chemotaxis in vitro toward live pathogenic amebae and amebic membranes (IP:0682:1 strain) compared to either the supernatant fraction or the nonpathogenic DKB or Laredo amebae. The results of this study indicate that membrane bound proteins of pathogenic amebae are chemotactic for gerbil neutrophils which may be important in the pathogenesis and pathology of amebiasis.

Animals

[Acetylcholinesterase titers in the amniotic fluid. Value of screening dysraphia of the central nervous system].

The authors report the results of 434 titrations of acetylcholinesterase in the amniotic fluid sampled by early amniocentesis, between the 17th and 24th week of amenorrhea. The biochemical technique used was quantitative and the values of the total cholinesterase activity (TchE) and the true acetylcholinesterase (AchE) were studied separately. Their conclusion is similar to that of other authors: the quantitative method, although satisfactory, has less value than the qualitative method using electrophoresis on polyacrylamide gel in order to screen or confirm the existence of a dysraphia of the central nervous system, because any amount of soiled fetal blood elevates the acetylcholinesterase level, titrated by the quantitative method.

Acetylcholinesterase

In vitro and in vivo interaction between trophozoites of Entamoeba histolytica and gerbil lymphoid cells.

The in vitro and in vivo antiamoebic cytotoxic effects of peritoneal exudate cells and mesenteric lymph node lymphocytes of gerbils with cecal amoebiasis or those immunized with amoebic extract were investigated. A differential effect of the lymphoid cells against trophozoites of nonpathogenic and pathogenic strains of Entamoeba histolytica was observed. Nonpathogenic amoebae were more susceptible to killing by lymphoid cells than pathogenic amoebae in vitro and in vivo in infected or immunized animals. These data suggest that during the course of cecal amoebiasis in gerbils, a differential stimulation or depletion of cytotoxic cells in the lymphoreticular tissues occurs, resulting in an impaired cell-mediated immune response.

Animals

[Determination of the acetylcholinesterase activities of the amniotic fluid on a centrifugal analyzer].

Amniotic fluid cholinesterase (ChE) activity measurements are realized to detect pre-natal neural tube defects. Their determinations on centrifugal analyzer are described. Total ChE activity is assayed at 412 nm with dithiobis-(nitrobenzoic-acid). Acetylcholinesterase activity is measured in the presence of ChE inhibitor, 14 X 10(-6)M lysivane; our results about the inhibitor concentration confirm the previous studies of Dale (Clin. Chim. Acta, 1977, 77, 407-413, Lancet, 1980, ii, 975) in opposition to those of Brock (Lancet, 1981, i, 95). Non NTD amniotic fluids from 92 women between the 17th and 20nd weeks of pregnancy were used to establish normal values. The technique proposed is rapid, accurate and needs only 40 microliters sample.

Acetylcholinesterase

[Arsenism: a case-report (author's transl)].

Among the multiple clinical features encountered in arsenism the most striking are hematological (leucopenia, macrocytic anemia), neurological, digestive, and cardiovascular. Diagnostic rests on the assay of the arsenic content of hair and urine. D-penicillamine appears to be the best therapy. However, late development of cancer of the skin or of internal organs remains possible. The authors report a case of arsenism and review the aspects of this rare disease.

Aged

[Pulmonary involvement in chronic lymphocytic leukemia. Diagnostic value of trans-bronchial biopsy (author's transl)].

Pulmonary parenchymatous involvement in a patient with chronic lymphocytic leukemia (CLL) was demonstrated by trans-bronchial pulmonary biopsy using a flexible endoscope. This procedure is clearly of value in similar cases when clinical and roentgenological examinations are insufficient. The observed cases provides the opportunity for a brief chronological review of the literature. Advances in the classification of CLL, which follow the technological improvements, are described as well as their bearing on management and prognosis of this condition.

Biopsy