Effects of IFN-gamma and interleukin-1beta on major histocompatibility complex antigen and intercellular adhesion molecule-1 expression by 9L gliosarcoma: relevance to its cytolysis by alloreactive cytotoxic T lymphocytes.

To enhance the efficacy of cellular immunotherapy for gliomas, we tested the concept of using proinflammatory cytokine treatment with interferon-gamma (IFN-gamma) or interleukin-1beta (IL-1beta) or both to render glioma cells more susceptible to cytolysis by alloreactive cytotoxic T lymphocytes (aCTL). The cytokines, separately or in combination, were able to upregulate major histocompatibility complex (MHC) class I antigen or intercellular adhesion molecule-1 (ICAM-1) on Fischer rat 9L gliosarcoma cells. 9L cells were incubated in vitro for 24, 48, or 72 h with varying concentrations of rat IFN-gamma (0-2000 U/ml) or recombinant human IL-1 (rHUIL-1) (0-1000 U/ml) or both. By 48 h, IFN-gamma (500 U/ml) maximally induced the percentage of positive expressing cells and the relative antigen density of MHC class I and ICAM-1 on 9L cells, whereas IL-1 induced only ICAM-1 expression. Simultaneous incubation of IL-1 with IFN-gamma did not further affect the induction of class I on 9L cells more than that achieved with IFN-gamma alone. 9L cells with upregulated MHC class I and ICAM-1 expression were more sensitive to lysis by aCTL in in vitro cytotoxicity assays, regardless of whether the precursor aCTL came from naive or from 9L-immunized rats. Furthermore, inhibition of 9L cytotoxicity in assays that included blocking antibodies to MHC class I or to ICAM-1 revealed that T cell receptor (TCR) interactions with MHC class I and that ICAM-1 interactions with lymphocyte function-associated-1 (LFA-1) antigen account for a portion of the glioma lysis by aCTL.     

Atypical complication of surgery for otospongiosis: the formation of cholesteatoma

Presenting a clinical case, the authors reveal the possible cholesteatoma complications arising from otospongious surgery. He notice that there are very few literature about similar cases. Underlining the rarity of this complication, the authors will put forward concisely the principal etiological mechanisms occurring in this kind of pathology. Since the reoperation must often be carried out on fragile inner ears, the authors stress on the necessity to respect the elementary rules of prevention in order to avoid the formation of precholesteatoma states.     

Brainstem anaesthesia after peribulbar anaesthesia

Purpose  To present a case of brainstem anaesthesia as a complication of peribulbar anaesthesia. Clinical features  A 75-yr-old woman received peribulbar anaesthesia for cataract surgery. A few seconds after the block was performed, she had a respiratory arrest, became unconscious, and developed hypertension and tachycardia followed by hypotension and bradycardia. Ventilatory and haemodynamic support were performed before the patient regained adequate spontaneous breathing and normal heart rate and blood pressure. Conclusion  Peribulbar anaesthesia generally cames a low risk of serious complications. However, respiratory arrest and brainstem anaesthesia may occur as complications of peribulbar blocks.

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Résumé Objectif  Présenter un cas d’anesthésie du tronc cérébral compliquant une anesthésie péribulbaire. éléments cliniques  Un bloc péribulbaire était réalisé chez une femine de 75 ans pour l’extraction d’une cataracte. Quelques secondes après l’injection, la patiente cessait de respirer et perdait conscience. Elle devenait hypertendue et tachycarde puts hypotendue et bradycarde. La ventilation et la circulation devaient être supportées jusqu’au retour spontané à la normale. Conclusion  En général, l’anesthésie péribulbare comporte un faible risque de complications sérieuses. Un arrêt respiratoire par anesthésie du tronc cérébral est toujours possible.

     

Thrombin is the major serum factor stimulating phosphoinositide turnover, but not DNA synthesis in human neuroblastoma SH-EP cells.

Fetal calf serum stimulates both phosphoinositide turnover and DNA synthesis in SH-EP cells. The phosphoinositide turnover-stimulating activity of serum is largely (70%) reduced in the presence of hirudin, a blocker of thrombin activity. Yet, hirudin does not alter the ability of serum to stimulate DNA synthesis. Purified alpha-thrombin is a potent (EC50, 35 pM) stimulator of phosphoinositide turnover in SH-EP cells, but induces DNA synthesis only at much higher concentrations (10 nM-1 microM). Thus, serum thrombin accounts for most of the ability of serum to stimulate phosphoinositide hydrolysis, but not for the effect of serum on cell division, since the concentration of thrombin in serum is not sufficient to induce DNA synthesis. These data suggest that hydrolysis of inositol lipids may not be the main signalling event mediating the mitogenic effects of alpha-thrombin.     

Evaluation of local cerebral glucose utilization and the permeability of the blood-brain barrier in the genetically epilepsy-prone rat

Summary The genetically epileptic-prone rat (GEPR) is a valuable model for the study of gene-linked abnormalities involved in epilepsy. In comparison with normal Sprague-Dawley controls, we found, in GEPRs, a marked depression in local cerebral glucose utilization, widespread throughout the brain. This depression was accompanied by a significant increase of blood-brain barrier permeability and a reduction in regional blood volume. Finally GEPRs showed lower plasma levels of total triiodothyronine than normal controls. One can speculate that alterations in cerebral metabolism and microvascular regulation and thyroid hormone imbalance may be gene-linked factors involved in seizure susceptibility.     

Modulation of (+)-[3H]pentazocine binding to guinea pig cerebellum by divalent cations.

The ability of cations to modulate the binding of the sigma 1 receptor-selective ligand (+)-[3H]pentazocine to guinea pig cerebellum was investigated. Di- and trivalent cations biphasically inhibited (+)-[3H]pentazocine binding, revealing multiple affinity states. The rank order of potency of these cations (based on the high affinity component of inhibition) was Zn2+ > Co2+ > La3+ = Ni2+ = Cd2+ = Mn2+ = Gd2+ > Ba2+ = Sr2+ > Mg2+ > Ca2+. The inhibition of 1,3-[3H]di(2-tolyl)guanidine binding to the sigma 2 receptor by these cations differed qualitatively and quantitatively from their effects on (+)-[3H]pentazocine binding. Although monovalent cations decreased the Kd for (+)-[3H]pentazocine binding, divalent cations split (+)-[3H]pentazocine binding into low and high affinity components. The Bmax of the high affinity component decreased with increasing divalent cation concentrations. Both mono- and divalent cations significantly reduced the rate of association of (+)-[3H]pentazocine with the sigma 1 receptor without altering the dissociation rate. (+)-[3H]Pentazocine binding was not altered by guanine nucleotides or by treatment with cholera or pertussis toxins. However, nonselective cation channel blockers (cinnarizine, hydroxyzine, prenylamine, amiodarone, and proadifen) potently inhibited (+)-[3H]pentazocine binding. These results indicate that physiologically relevant concentrations of divalent cations allosterically modulate (+)-[3H]pentazocine binding to the sigma 1 receptor, to reveal multiple affinity states. These sites do not represent sigma 1 to sigma 2 subtype interconversion or ternary complex formation with guanine nucleotide-binding proteins. However, the rank order of cation potency and the inhibition of binding by cation channel blockers is consistent with a potential role for sigma receptors as constituents of cation channels.     

Peripheral hemodynamic and humoral effects of oral zofenopril calcium (SQ. 26,991) in patients with congestive heart failure

In 14 patients with congestive heart failure (CHF) of various grade (NYHA class 2-4) the effects of zofenopril calcium (SQ 26,991) on blood pressure and forearm circulation were studied by venous occlusion plethysmography. Changes in plasma renin activity (PRA), aldosterone, Atrial natriuretic factor (ANF) and arginine-vasopressin (AVP) were also measured. Two hours after oral administration of 7.5 mg of zofenopril we observed a decrease in blood pressure, heart rate, and forearm vascular resistance along with an increase in venous distensibility. Zofenopril also decreased ANP levels in a manner directly related to peripheral venodilatation (r = .64; P less than .05) and modified arginine-vasopressin (AVP) proportionally to the fall in blood pressure observed in response to drug administration (%SBP/%AVP: r = .64, P less than .05; %DBP/%AVP: r = .67, P less than .05). Hemodynamic and humoral responses to zofenopril occurred without any significant unwanted adverse reaction, even in patients with greater pressor reduction. We conclude that oral acute zofenopril administration, in patients with congestive heart failure, causes an arterial and venous forearm vasodilatation which is probably involved in the acute changes in plasma levels of ANF and AVP observed after drug administration.     

Activation of two different but complementary biochemical pathways stimulates release of hypothalamic luteinizing hormone-releasing hormone.

Evidence exists that a norepinephrine/prostaglandin E2 (PGE2)/cAMP pathway is involved in the regulation of luteinizing hormone-releasing hormone (LHRH) secretion. The aim of the present experiments was to determine if release of LHRH from the immature rat hypothalamus could also be stimulated by activation of protein kinase C. Median eminences from 28-day-old female rats were incubated in vitro with either dioctanoylglycerol (a synthetic diacylglycerol that selectively activates protein kinase C in intact cells) or 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (another protein kinase C activator). Both agents increased LHRH release, the response to dioctanoylglycerol being more pronounced than that to the phorbol ester. This direct activation of protein kinase C was not accompanied by changes in PGE2 formation. Activation of the PGE2/cAMP pathway by either norepinephrine, PGE2, or forskolin (a stimulator of adenylate cyclase) increased LHRH release. Dioctanoylglycerol or phorbol ester in conjunction with either norepinephrine, PGE2 or forskolin resulted in an additive effect on LHRH release suggesting coexistence of both pathways. Phospholipase C, which activates protein kinase C via formation of diacylglycerol, increased the release of both LHRH and PGE2. This suggests that an increase in endogenous phospholipase C activity caused by neurotransmitter inputs may lead to both activation of protein kinase C and PGE2 formation. Blockade of cyclooxygenase activity by indomethacin obliterated phospholipase C-induced PGE2 release. The same treatment reduced the LHRH response by only 50% indicating that protein kinase C activation can cause LHRH release in the absence of PGE2 synthesis. It is suggested that the median eminence of the rat possesses a protein kinase C-dependent pathway that is coupled positively to LHRH release and complements PGE2/cAMP-dependent mechanisms. Norepinephrine, however, does not appear to be the neurotransmitter responsible for activating the protein kinase C pathway. Simultaneous activation of both pathways may provide a mechanism by which a large increase in LHRH secretion occurs, such as in the afternoon of first proestrus.