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Biomedical subjects

A Morin

Publications and source records attributed to A Morin.

At least 19 recordsLinked to original sources

Polyadenylic: polyuridylic acid-induced determinants of host resistance to cytomegalovirus and their potentiation by hyperthermia.

The ability of spleen cells from poly A:poly U-treated mice to inhibit murine cytomegalovirus (MCMV) replication in confluent monolayer cells of secondary mouse embryo fibroblasts (MEFs) cultured at 37 and 40 degrees C was investigated. When spleen cells from BALB/c mice injected 48 h earlier with poly A:poly U were added to MEFs infected 2 h previously with MCMV, 37% less plaques were observed than in cultures containing control cells. Of interest, the poly A:poly U-induced antiviral activity at the elevated temperature (40 degrees C) resulted in a further drop to 61% in MCMV-induced plaques compared to those of the normothermic (37 degrees C) cultures. The antiviral function of spleen cells induced by poly A:poly U was evident in the supernatant fluid when cultured for 48 h at 37 degrees C. MCMV-induced plaques were reduced to 52 and 5% of controls in the plaque assays performed at 37 and 40 degrees C, respectively. Supernatant fluids generated at 40 degrees C, however, inhibited MCMV replication only when incubated at 40 degrees C. No direct inhibitory effect of the supernatant fluids on MCMV was evident; rather, inhibition was effected directly on the MEFs. The NK cell fraction of spleen cells from poly A:poly U-treated mice alone showed only a slight inhibitory effect at 40 degrees C. However, in the presence of the supernatant fluid from poly A:poly U-exposed spleen cells, the antiviral activity of NK cells was significantly increased both at 37 and 40 degrees C. The cellular source of the culture fluid showing poly A:poly U-induced antiviral activity appeared to be in the T-cell population. It was completely neutralized by monoclonal anti-IFN gamma antibody but not by anti-IFN beta, anti-IL4, anti-transforming growth factor, or anti-prostaglandin E2. In conclusion, these data document the ability of spleen cells from poly A:poly U-treated mice to inhibit MCMV replication and this activity is potentiated by hyperthermic conditions. The antiviral function of poly A:poly U-treated spleen cells appeared to be due mainly to the action of IFN gamma produced by T cells. The enhanced antiviral activity by hyperthermia appeared to be related to the action of IFN gamma rather than its production.

Animals

Polyadenylic:polyuridylic acid-induced protection of BALB/c mice against acute murine cytomegalovirus infection.

Treatment of BALB/c mice with poly(A):poly(U) 18 h prior to infection with a lethal dose of murine cytomegalovirus (MCMV) increased survival. In parallel with increased survival, a 10- to 100-fold reduction of plaque-forming MCMV was found in the liver and spleen of mice 4 days post-infection with a sublethal dose of MCMV. Poly(A):poly(U) did not significantly increase natural killer cell activity or prolong the duration of elevated cytotoxic activity in infected animals. The possible role of interferon in the poly(A):poly(U)-induced protection of BALB/c mice is discussed.

Animals

[The role of gastrin releasing peptide as a lung growth factor].

The proliferation of the bronchial epithelium and tumors associated with this tissue is controlled by various growth factors. The main factor is Gastrin Releasing Peptide (GRP), the human counterpart of the amphibian bombesin. These neuropeptides also act as neuromediators and gut hormones. All peptides of this family share a conserved C terminal sequence which is required for biological activity. The determination of this sequence has provided the basis for the design of specific agonist and antagonist peptides and for the generation of monoclonal antibodies (Mab). GRP interacts with a receptor coupled to a G protein and the signalling process leads to the activation of phospholipase C and kinases, and the mobilization of calcium. GRP promotes the proliferation of foetal and adult bronchial epithelium and of small cell lung cancer (SCLC) cells. GRP is also an autocrine growth factor for some SCLC cell lines. The growth of these lines is reduced in vitro and in vivo by MAb and specific antagonists. Hyperplasia of GRP producing cells has been shown in various lung diseases in adults and children. Pharmacological data on GRP suggest that its antagonists could be used in the treatment of SCLC (in addition to chemotherapy) and of interstitial lung disease. The cloning of the GRP receptor should facilitate the design of specific and potent antagonists of the peptide.

Adult

Daily variations in concentration of vasoactive intestinal polypeptide immunoreactivity in discrete brain areas of the rat.

The concentration of VIP-like immunoreactivity (VIP-LI) was determined by radioimmunoassay at various times of the day in 11 discrete brain areas and in the antehypophysis of rats maintained on a regular 12 h/12 h light-dark cycle. In the suprachiasmatic and periventricular nuclei the VIP-LI increased during the dark period and decreased during the subsequent light period. In addition, the VIP-LI exhibited complex variations in the locus coeruleus, the periaqueductal gray matter and the paraventricular nucleus, but did not change in the other areas investigated.

Analysis of Variance

Visceral perception in health and functional dyspepsia. Crossover study of gastric distension with placebo and domperidone.

The symptoms of functional dyspepsia are still unexplained. To evaluate the possible role of abnormal visceral perception, we studied the symptomatic responses and the pressure variations during progressive gastric distension in 10 female healthy control subjects (mean age 33.6 years) and in 10 female patients with functional dyspepsia (mean age 35.2 years). A rubber balloon was positioned 4 cm below the lower esophageal sphincter (LES) and inflated with progressively larger volumes of air by steps of 50 ml; pressures at the gastric fundus and at the LES were continuously recorded by perfused manometric catheters. Each subject was studied on two separate occasions after randomized double-blind administration of either placebo or 20 mg of domperidone. Symptomatic responses and the manometric data were analyzed at the time of the initial recognition of distension (bloating step) and at the time of reporting pain or up to a maximum of 700 ml of balloon inflation (pain or 700-ml step). On placebo, the volumes of gastric distension were more than two times lower in patients than in control subjects at the bloating step (185 +/- 32 ml vs 470 +/- 40 ml, P = 0.001) and at the pain or 700-ml step (265 +/- 54 ml vs 600 +/- 34 ml, P less than 0.005), while the pressure gradients (pressure at inflation steps minus baseline pressure before beginning inflation) were not statistically different between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Secretogranin I (chromogranin B) mRNA accumulation is hormonally regulated in GH3B6 rat pituitary tumor cells.

Secretogranin I (SgI; chromogranin B) belongs to a class of acidic tyrosine-sulfated secretory proteins believed to play a role in the secretory process of endocrine cells. Our aim here was to compare the levels of SgI mRNA to that of prolactin (PRL) and growth hormone (GH), using rat pituitary cell lines. As far as the constitutive expression is concerned, we found a positive correlation between SgI mRNA and PRL mRNA levels. However, the neuropeptide TRH (50 nM) inhibited the accumulation of SgI mRNA in GH3B6 cells whereas, as expected, it induced a rapid and sustained increase in PRL mRNA accumulation. By contrast, 17 beta-estradiol (1 nM) stimulated the accumulation of both SgI and PRL mRNAs, with the same EC50 (18-59 pM). Reciprocally, treatment with dexamethasone (100 nM) reduced the level of SgI and PRL mRNAs to 23% and 29% of control, respectively, but led to a 2.1-fold increase in the GH mRNA level. Altogether, the present work shows that SgI gene expression is subject to multiple hormonal regulations and occasionally parallels the regulation of the PRL gene but never that of the GH gene, under the conditions tested.

Animals

Effect of hirudin on the chemotactic properties of alpha-thrombin.

A study by an agarose technique of the chemotactic power of human alpha-thrombin on polymorphonuclear leukocytes reveals that this enzyme has a chemotactic activity. Hirudin, which inhibits the coagulant properties of thrombin, suppresses these chemotactic properties. This effect could be explained by the binding of hirudin to the structural domain of alpha-thrombin involved in its chemotactic activity.

Binding Sites

Localization of the structural domain responsible for the chemotactic properties of thrombin on polymorphonuclear leukocytes.

Human alpha thrombin at 1.1.10(-5) M is chemotactic for human polymorphonuclear leukocytes. This thrombin property disappears when the alpha thrombin (1.1.10(-5) M) hirudin (1.32.10(-5) M) mixture is realized. The same result is obtained when the thrombin at 1.1. 10(-5) M is inhibited by antithrombin III in a ratio of 1 mol of thrombin for 4.5 mol of antithrombin III. The hirudin and the antithrombin III appear therefore to mask, by their binding the structural domain responsible for the chemotactic properties of thrombin on polymorphonuclear leukocytes.

Antithrombin III

Coagulation impact on chemotactic activity generation for polymorphonuclear leukocytes.

Chemotactic technique in agarose gel has exposed the attractive properties of human alpha thrombin with respect to human polymorphonuclear leukocytes. The observed chemotaxis is maximal between 1.4.10-5 M and 1.6.10-5 M but extends from 2.8.10-6 M to 2.2.10-5 M. Human prothrombin, in an identical concentration zone as that studied for thrombin shows no chemotactic activity on the polymorphonuclear leukocytes. During coagulation the formed alpha thrombin attracts the polymorphonuclear leukocytes to it's formation site.

Chemotactic Factors

Triiodothyronine inhibits transcription from the human growth hormone promoter.

Three DNA constructs, the natural human growth hormone gene (hGH-hGH) its 500 bp promoter linked to the chloramphenicol acetyl transferase reporter gene (hGH-CAT), and its structural part linked to the herpes virus thymidine kinase promoter (TK-hGH) were introduced into rat pituitary GC cells by DEAE-dextran transfection. Transient expression was followed as a function of triiodothyronine (T3) concentration. The hGH-CAT expression was specifically inhibited by T3 following a typical dose-response curve while hGH-GH gene expression was not significantly modified. The transient expression of TK-hGH increased as a function of T3 concentration. These results indicate that T3 exerts two opposite effects on hGH gene expression. First, it down-regulates expression by acting on the promoter; second, it up-regulates expression by acting on the structural part of the gene. These action could be due to regulation of transcription and mRNA stabilization, respectively.

Animals

[Pygomelus. A single monster or a double monster?].

With an anatomical case and a clinical case, the authors describe the pygomelus, a very rare monstruosity. Legend and reality are often mixed in the description of literature. It is difficult to classify this monstruosity either in the simple monster or in the twin monsters.

Abnormalities, Severe Teratoid

Preferential role of calcium in the regulation of prolactin gene transcription by thyrotropin-releasing hormone in GH3 pituitary cells.

TRH induces two separate events in pituitary PRL cells. It increases the release of stored PRL and enhances the rate of PRL gene transcription, which results in an increased steady state concentration of PRL messenger RNA (mRNA) and a concomitant augmentation of PRL production. The mechanisms underlying the release process involve the activation of phosphatidylinositol turnover which generates inositol 1,4,5-trisphosphate and 1,2-diacylglycerol. In order to determine whether these intracellular messengers also mediate the stimulation of PRL gene expression by TRH, we have correlated the level of receptor occupancy with the rate of gene transcription and investigated the action of drugs which increase cytosolic calcium or activate protein kinase C. We have determined that sustained stimulation of transcription requires the persistent occupancy of a limited number of TRH receptor sites and that the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), calcium ionophores (A23187, ionomycin), and the calcium channel agonist BAY K 8644 enhance PRL gene transcription. However, TPA is less potent and ionomycin requires a low concentration of TPA to fully mimic TRH action, whereas BAY K 8644 alone displays the same potency as TRH. The effects of BAY K 8644 and TRH are not additive and thus suggest that the influx of calcium plays a predominant role in the regulation of PRL gene transcription by TRH.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy

[Pygomelus].

With an anatomical case and a clinical case, the authors describe the pygomelus, a very rare monstruosity. Legend and reality are often mixed in the description of literature. It is difficult to classify this monstruosity either in the simple monster or in the twin monsters.

Abnormalities, Severe Teratoid

Modulation of natural killer activity by muramyl peptides: relationship with adjuvant and anti-infectious properties.

Natural killer (NK) activity of spleen cells was studied in DBA/2 mice, 24 and 72 h after intravenous injection of various muramyl peptides: muramyl dipeptide (MDP) and derivatives which are both adjuvant-active and able to increase resistance against Klebsiella pneumoniae; derivatives which are adjuvant-active but devoid of anti-infectious properties; derivatives which are anti-infectious but devoid of adjuvant activity, and derivatives which are devoid of both activities such as the stereoisomer MDP[D-Ala]1. An early increase in NK activity was observed 24 h after injection of all nonadjuvant derivatives, whatever their effect on infection. A stimulation of natural cytotoxicity was always induced 72 h after injection of MDP and derivatives able to protect mice against Klebsiella pneumoniae infection. So, even if the reverse was not true, there seems to exist some correlation between the anti-infectious effect of muramyl peptides and the late increase in NK activity. The modulation of NK activity by muramyl peptides appeared to be independent of interferon production. Moreover, inhibition of the stimulatory effect by a cell cycle-specific drug, hydroxyurea, observed 72 h after MDP suggests a requirement for proliferation.

Acetylmuramyl-Alanyl-Isoglutamine

The role of cyclic GMP in cells with the properties of smooth muscle cultured from the rat myometrium.

Cells growing in culture with previously described properties of rat uterine smooth muscle accumulated 45Ca2+ from the medium. Ca2+ uptake by these cells was stimulated by the addition to the medium of 8-bromo-cGMP but not by 8-bromo-cAMP. Ca2+ uptake was also stimulated by carbachol and by the nitro-vasodilator nitroprusside. Although cholinergic agonists have been shown previously to stimulate contraction but not cGMP synthesis in the rat myometrium, both carbachol and nitroprusside stimulated cGMP production by the cultured cells. These results suggested the cells had cholinergic receptor-mediated functions that reflected some neurotransmitter-sensitive properties of uterine smooth muscle in situ. When determined by a specific radioligand binding assay, subcellular fractions of the cultured cells bound muscarinic cholinergic agonists and antagonists with affinities expected of the muscarinic receptor. The cells were also sensitive to the beta-adrenergic catecholamine agonist isoproterenol, which stimulated cAMP production but not Ca2+ uptake. Carbachol failed to inhibit isoproterenol-dependent cAMP production, which is an important property of the cholinergic receptor in uterine smooth muscle in situ. These results suggest some but not all acetylcholine-sensitive properties of uterine smooth muscle may be retained in cell culture.

8-Bromo Cyclic Adenosine Monophosphate