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D Ungureanu

Publications and source records attributed to D Ungureanu.

At least 19 recordsLinked to original sources

Vaccination with tumor cells engineered to secrete interleukin 2-immunoglobulin G fusion protein induces tumor rejection.

Here we provide proof that the injection of tumor cells engineered to secrete interleukin 2 (IL-2)-IgG chimeric proteins locally induces potent antitumor responses, which are more effective than tumor transfection with IL-2 alone. Murine plasmacytoma cells (J558L) were stably transfected with DNA coding for a human IL-2-IgG1 or a murine IL-2-IgG2b fusion protein and were injected s.c. into syngeneic BALB/c mice. Evaluation of tumor growth and rejection patterns showed that IL-2-IgG secretion by transfected J558L tumor cells induced their rejection in all animals tested, similar to the rejection of J558L cells engineered to secrete IL-2 alone, whereas treatment with parental cells was lethal. However, mice treated with IL-2-IgG-secreting J558L cells (human IL-2-IgG1 and murine IL-2-IgG2b) exhibited a significantly stronger tumor immunity against a later challenge with parental J558L cells than mice treated with IL-2-secreting tumor cells.

Animals↗

IL-15-IgG2b fusion protein accelerates and enhances a Th2 but not a Th1 immune response in vivo, while IL-2-IgG2b fusion protein inhibits both.

We have explored how IL-15 influences Th1 or Th2 type immune response in vivo. Intraperitoneal application of an IL-15-IgG2b fusion protein (FP) to mice did neither significantly affect the footpad swelling nor the production of hemagglutinizing antibodies in a delayed type hypersensitivity reaction to sheep red blood cells. In contrast, in an established murine Th2 model of sensitization to ovalbumin (OVA), IL-15-IgG2b FP plus OVA sensitization resulted in massively accelerated and enhanced allergen-specific IgE and IgG1 antibody production. In vitro, stimulation of spleen cells from OVA-sensitized mice with OVA+IL-15 or OVA+IL-15-IgG2b resulted in a significantly enhanced IgE production. IL-4 secretion was significantly induced by IL-15 but not by IL-15-IgG2b. An IL-2-IgG2b FP with the same Fc tail as the IL-15-IgG2b FP was used as control in both models. In striking contrast to the IL-15-IgG2b FP, IL-2-IgG2b significantly inhibited the Th2 type antibody production in vivo. The current study suggests that IL-15-IgG2b may be employed as a potent accelerator and enhancer of Th2 type immune responses in vivo, while IL-2-IgG2b can suppress the latter.

Allergens↗

Interleukin-15 protects from lethal apoptosis in vivo.

Interleukin-15 shares many biological activities with IL-2 and signals through the IL-2 receptor beta and gamma chains. However, IL-15 and IL-2 differ in their controls of expression and secretion, their range of target cells and their functional activities. These dissimilarities may include differential effects on apoptosis. For example, IL-2 induces or inhibits T-cell apoptosis in vitro, depending on T-cell activation, whereas IL-15 inhibits cytokine deprivation-induced apoptosis in activated T cells. Studying whether and how IL-15 modulates distinct apoptosis pathways, we show here that apoptosis induced by anti-Fas, anti-CD3, dexamethasone, and/or anti-IgM in activated human T and B cells in vitro is inhibited by IL-15 in a manner dependent on RNA synthesis. In vivo, anti-Fas-induced lethal multisystem apoptosis in mice is suppressed by a novel IL-15-IgG2b fusion protein. Only IL-15, but not IL-2, completely protected from lethal hepatic failure. Thus, IL-15 is a potent, general inhibitor of apoptosis in vitro and in vivo with intriguing therapeutic potential.

Animals↗

[Stenosing hypertrophic antromyopathy].

The authors describe a case of insufficiency of gastric evacuation, due to the a very rare injury of the antrum which they called:--"hypertrophic and stenosing antromiopathiae". By similarity with the pilor hypertrophy, but without altering the pilor which is intact, the hypertrophy involves especially the gastric antrum, the muscular tunic--mainly the circular fibres in the absence of any acute or chronic inflammatory process. In the interstice between the muscular fibres, there appear collagen fibres in spiral disposition, probably in a contraction. Due to the similitude of the clinical syndrome, the described disease could be ranged among the stenosant diseases of the pyloric pole of the stomach. Out of these, more frequently pointed out, although very rare too, seems to be the pilor hypertrophy at adults. Mention must be made that the two diseases are completely different, because in the "Hypertrophic and stenosing antromiopathiae", the pilor is macroscopic and at the same time normal from the histopathologic aspect point of view.

Adult↗

[Intra-abdominal fibromatosis].

The authors describe three cases of intraabdominal fibromathosis: two cases with intraperithoneal location and another one with retroperithoneal location. All of them are benign noncapsulated tumours of the fibrous tissue with tendancy to local recurrence. Abdominal fibromathosis may determine any form of acute or chronic digestive manifestations. Only to the accuracy of the histo-pathological examination is due the diagnosis between fibromathosis and fibrosarcoma, reactive fibrosis, mixoma and nodular fasceitis. The surgical excision must not be economical and the association with radiant therapy must also be considered.

Adult↗

Abnormal contractile function due to induction of nitric oxide synthesis in rat cardiac myocytes follows exposure to activated macrophage-conditioned medium.

The mechanism by which soluble mediators of immune cell origin depress myocardial contractility, either globally as in systemic sepsis, or regionally in areas of inflammatory myocardial infiltrates, remains unclear. When freshly isolated ventricular myocytes from adult rat hearts were preincubated for at least 24 h in medium conditioned by endotoxin (LPS)-activated rat alveolar macrophages, their subsequent inotropic response to the beta-adrenergic agonist isoproterenol was reduced from 225 +/- 19% to 155 +/- 10% of the baseline amplitude of shortening (mean +/- SEM, P < 0.05). Neither baseline contractile function nor the contractile response to high extracellular calcium were affected. To determine whether an endogenous nitric-oxide (NO)-signaling pathway within ventricular myocytes was responsible for their decreased responsiveness to isoproterenol, the L-arginine analogue L-NMMA was added to the preincubation medium. While L-NMMA did not affect baseline contractile function or the response of control myocytes to isoproterenol, it completely restored the positive inotropic response to isoproterenol in myocytes preincubated in LPS-activated macrophage medium. Release of NO by ventricular myocytes following exposure to activated macrophage medium was detected as an increase in cGMP content in a reporter-cell (RFL-6) bioassay and also as increased nitrite content in myocyte-conditioned medium. Thus, the depressed contractile response of adult rat ventricular myocytes to beta-adrenergic agonists by a 24-h exposure to soluble inflammatory mediators is mediated at least in party by induction of an autocrine NO signaling pathway.

Animals↗

The orbicularis oculi and the adductor pollicis muscles as monitors of atracurium block of laryngeal muscles.

The aim of this study was to determine whether atracurium-induced neuromuscular block at the laryngeal adductor muscles could be predicted by visual inspection of either adductor pollicis or orbicularis oculi responses. Twenty-one ASA Class I or II patients were anesthetized with propofol (2-2.5 mg/kg) and fentanyl (2-5 micrograms/kg). Tracheal intubation was performed without neuromuscular blocking drugs. Patients were assigned randomly to receive atracurium 0.3 or 0.5 mg/kg intravenously. Train-of-four stimulation was applied to the ulnar, facial, and recurrent laryngeal nerves. Laryngeal response was measured as the pressure change in the tracheal tube cuff positioned between the vocal cords. The response at the adductor pollicis and orbicularis oculi was evaluated visually by two observers who detected if and when block was complete. Twelve patients, including all those receiving 0.5 mg/kg, had complete orbicularis oculi block. The same patients, except one, also had 100% laryngeal block. Adductor pollicis response was abolished in the same 12 patients plus an additional 4 patients. In patients receiving atracurium 0.5 mg/kg, laryngeal and orbicularis oculi responses were abolished faster (mean +/- SD: 132 +/- 80 and 146 +/- 58 s, respectively) than the adductor pollicis muscle (243 +/- 55 s; P < 0.05). There was a significant correlation (r = 0.94; P < 0.001) between neuromuscular block onset time at the laryngeal adductor and orbicularis oculi muscles but not between laryngeal and thumb muscles. The authors conclude that, after injection of atracurium, laryngeal adductor and orbicularis oculi blocks have similar intensities and time courses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Ultrarapid induction.

We report 250 rapid induction anesthesias performed for the purpose of preventing regurgitation and vomiting in patients with full stomach. The anesthetic technique includes administration of morphine 20 mg and droperidol 5 mg intravenously 10-15 minutes before induction, a voluntary air hyperventilation at the anesthetist's command, during which induction drugs are introduced and an induction with a mixture containing suxamethonium 2 mg/kg and thiopentone 1.4 mg/kg, administered within 1-2 seconds. Eighteen seconds after the onset of injection the loss of lid reflex is observed followed 7 seconds later by masseter muscle relaxation. Within the following 5-10 seconds intubation is carried out in full fasciculation process, before cardia relaxation. With this technique, a mean intubation time of 35 seconds is achieved. The interval of maximum regurgitation risk is lowered to 15 seconds, so that ventilation by mask and cricoid pressure are no more necessary. The technique is indicated in the young and vigorous adult and contraindicated in the old and tainted patient, in coronary patients, in those with low heart output and slowing of circulation.

Adolescent↗

Deuterium oxide effects upon three parameters characterizing the activity of glycerol-extracted muscle: phosphate release, ATP-induced shortening, and 22Na+ distribution.

ATP splitting activity is progressively reduced with increasing heavy water (D2)) concentration. In contrast, sarcomere shorteining inhibition produced by D2O does not significantly depend on its concentration. Even at low concentration, the presence of D2O does reduce the excessive accumulation of radioactive sodium within glycerinated frog muscle. These heavy water effects on muscular contraction and soidum distribution can be interpreted to indicate adsorbed water within the cells. Evaluation of these experimental results in terms of Gibbs free enthalpy of binding at the adsorption sites of D20 or H20 is in good agreement with the data in the literature.

Adenosine Triphosphatases↗

The gastrointestinal tract in hypokinetic rats.

In Wistar rats kept for 15, 30 and 60 days in a hypokinetic state in special cages, alteration of some gastrointestinal glands was studied by means of histochemical and electron microscopic methods. After 15-30 days of hypokinesia, a decrease was found in the muco-polysaccharide content of the submaxillary, gastric and duodenal glands. The intestinal goblet cells appeared vacuolated. The oxyntic cells, which secrete HCl, as well as the G antral cells, which secrete gastrin, were in an active state. The hypokinetic rats exhibited increased gastric secretion. The electron microscopic aspect of the principal cells corresponded to augmented pepsin secretion. The enterocytes showed an increase in their leucine aminopeptidase, acid phosphatase and glucose-6-phosphatase content. In the submucosa of the fundus of the stomach an accumulation of eosinophils was observed. These modifications were more striking after 15 than after 30 days, and disappeared after 60 days of hypokinesia. These morphological and functional changes may be explained by glucocorticoid hypersecretion corresponding to a stress reaction.

Acid Phosphatase↗

Modifications of ouabain inhibition of xenon accumulation in red blood cells. Implications regarding cell water structuring.

Ouabain is known to depress uptake of xenon by red blood cells, but it is now found that the depressive effects of phenolsulfonphthalein (PSP) or heavy water are even more marked. Ouabain partly reverses those effects in a manner suggesting it exerts a constant action on xenon exchange regardless of the presence or absence of PSP or D2O. Processes analogous to exchange diffusion between certain anesthetic substances and xenon were also observed. The theoretical consequences of the findings are discussed.

Cell Membrane Permeability↗

Biochemical changes in the rat brain associated with dinitrophenol-induced brain edema.

The present paper was designed to the study of cerebral edema induced by intracarotid infusion of dinitrophenol. The determinations included variations in three lysosomal enzymes (acid phosphatase, cathepsin C and beta-glucuronidase), Na+-K+-ATP-ase, changes in cerebral RNA and protein concentrations and the synthesis of these macromolecules in vitro. In experimental brain edema a drastic drop in the activity of lysosomal enzymes took place. The acid phosphatase decreased to less than 30% of controls. Cathepsin C and beta-glucuronidase were reduced about 30% and 50% of control levels respectively. Protein concentration in the cerebral tissue also decreased by more than 50%. The concentration of RNA, RNA synthesis, and the level of Na+-K+-ATP-ase remained unchanged. Protein synthesis was stimulated by 75% (against controls). All these phenomena were suppressed when the animals subjected to the action of dinitrophenol were concomitantly treated with the antiacidotic substance, tris (hydroxymethyl) aminomethane.

Acid Phosphatase↗

Potassium and sodium ions in the glycerinated skeletal muscle. Distribution changes induced by adenosine triphosphate and nondissociable anesthetic substances.

Investigation of the ionic behavior of glycerinated muscle fibers showed that the residual structures of this biologic cellular material, lacking functional membranes, are able to discriminate between alkaline ions. The characteristics of the ionic selectivity of the glycerinated fibers change with their functional state and with the presence in the medium of certain nonionic substances. Among the more important features of ionic distribution between the membrane-free fibers and the medium are the following: (1) There is evident adsorption of potassium on the fibers, in the absence of ATP. (2) This adsorption increases in contraction and decreases in relaxation. (3) At high ionic concentrations, in contrast to what occurs at low potassium concentrations, the glycerinated muscle prefers sodium to potassium, but even under these conditions both ions are accumulated in the fibers to far greater levels than in the medium. This strongly suggests a Donnan ionic equilibrium developing parallel to the adsorption process. (4) Nonionic substances of the general anesthetic group markedly alter the ionic selectivity of the glycerinated fibers, probably by their action on the water's physical state. A mechanism is proposed for the observed ionic adsorption specific of the muscle-a mechanism in which actin-myosin coupling plays the cardinal adsorption role. In the general interpretation of the data a synthetic concept is advanced according to which an entire set of processes and factors concurs with the distribution of ions between the muscle and the medium.

Adenosine Triphosphate↗

Similitudes and differences in the reactivity of the liver cell chromatin to thioacetamide and hydrocortisone. Electron microscopic and cytochemical quantitative data concerning the chromatin condensation-dispersion cycle.

The administration of thioacetamide (TAA) and/or hydrocortisone to rats brought about dispersion of the heterochromatin in the liver cell, and concomitant stimulation of RNA synthesis in the chromatin. In contrast to other experimental situations in which dispersion of the chromatin persisted for at least 6 hours, after TAA injection dispersion was followed by rapid excess condensation. A hypothesis is suggested concerning the process of induction of malignant proliferation by TAA.

Acetamides↗