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1.
Brain Behav Immun ; 93: 226-237, 2021 03.
Article in English | MEDLINE | ID: mdl-33516921

ABSTRACT

While toll-like receptors (TLRs), which mediate innate immunity, are known to play an important role in host defense, recent work suggest their involvement in some integrated behaviors, including anxiety, depressive and cognitive functions. Here, we investigated the potential involvement of the flagellin receptor, TLR5, in anxiety, depression and cognitive behaviors using male TLR5 knock-out (KO) mice. We aobserved a specific low level of basal anxiety in TLR5 KO mice with an alteration of the hypothalamo-pituitary axis (HPA) response to acute restraint stress, illustrated by a decrease of both plasma corticosterone level and c-fos expression in the hypothalamic paraventricular nucleus where TLR5 was expressed, compared to WT littermates. However, depression and cognitive-related behaviors were not different between TLR5 KO and WT mice. Nor there were significant changes in the expression of some cytokines (IL-6, IL-10 and TNF-α) and other TLRs (TLR2, TLR3 and TLR4) in the prefrontal cortex, amygdala and hippocampus of TLR5 KO mice compared to WT mice. Moreover, mRNA expression of BDNF and glucocorticoid receptors in the hippocampus and amygdala, respectively, was not different. Finally, acute intracerebroventricular administration of flagellin, a specific TLR5 agonist, or chronic neomycin treatment did not exhibit a significant main effect, only a significant main effect of genotype was observed between TLR5 KO and WT mice. Together, those findings suggest a previously undescribed and specific role of TLR5 in anxiety and open original prospects in our understanding of the brain-gut axis function.


Subject(s)
Anxiety , Toll-Like Receptor 5 , Animals , Anxiety/genetics , Anxiety Disorders , Corticosterone , Male , Mice , Mice, Knockout , Toll-Like Receptor 5/genetics
2.
Bull Entomol Res ; 108(2): 213-222, 2018 Apr.
Article in English | MEDLINE | ID: mdl-28891460

ABSTRACT

Cixiid planthoppers are considered of major economic importance, as they can transmit phytoplasmas responsible for many plant diseases. While thorougly studied in vineyards, the epidemiology of stolbur phytoplasma, transmitted by Hyalesthes obsoletus Signoret, was rarely investigated on minor crops as lavender, where it leads to 'yellow decline' disease and large economic losses. The objective of this paper is to understand the effect of the local landscape characteristics on the presence and density of H. obsoletus in the 'Plateau de Valensole', southern France. Potential host plants of H. obsoletus were surveyed in three contrasted zones (in terms of crops and disease intensity), by uprooting plants and capturing adults in emergence traps. The localization and potential movements of H. obsoletus from the host plants towards lavandin (infertile hybrid of lavender) were determined using yellow sticky traps. Clary sage plants were found as major hosts of H. obsoletus. Flying insects were also caught in fields of lavandin, although emergence traps and plant uprooting did not confirm this crop as a winter host, i.e., as a reservoir for the insect. Based on one zone, we showed that attractiveness may depend on crop (clary sage or lavandin) and on its age, as well as on the distance to the supposed source field. These results suggest that clary sage could be an important host of H. obsoletus, whose density largely varies between zones. Genetic studies would be required to confirm the role of clary sage in the dissemination of yellow decline of lavandin.


Subject(s)
Hemiptera , Herbivory , Insect Vectors , Animals , Larva
3.
Antimicrob Agents Chemother ; 59(8): 5010-3, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25987610

ABSTRACT

The most deadly outbreak of Escherichia coli O104:H4 occurred in Europe in 2011. Here, we evaluated the effects of the retrograde trafficking inhibitor Retro-2(cycl) in a murine model of E. coli O104:H4 infection. Systemic treatment with Retro-2(cycl) significantly reduced body weight loss and improved clinical scores and survival rates for O104:H4-infected mice. The present data established that Retro-2(cycl) contributes to the protection of mice against O104:H4 infection and may represent a novel approach to limit Shiga toxin-producing Escherichia coli (STEC)-induced toxicity.


Subject(s)
Benzamides/pharmacology , Enterohemorrhagic Escherichia coli/drug effects , Escherichia coli Infections/drug therapy , Hemolytic-Uremic Syndrome/drug therapy , Shiga Toxin 2/antagonists & inhibitors , Thiophenes/pharmacology , Animals , Benzamides/therapeutic use , Chlorocebus aethiops , Disease Models, Animal , Disease Outbreaks , Enterohemorrhagic Escherichia coli/genetics , Enterohemorrhagic Escherichia coli/pathogenicity , Escherichia coli Infections/epidemiology , Europe , HeLa Cells , Hemolytic-Uremic Syndrome/prevention & control , Humans , Mice , Mice, Inbred BALB C , Thiophenes/therapeutic use , Vero Cells
4.
J Fr Ophtalmol ; 47(7): 104215, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38843609

ABSTRACT

Perivascular epithelioid cell tumors (PEComas) are a family of benign neoplasms characterized by smooth muscle and melanocytic differentiation. Orbital cases are rare. A 9-year-old male presented with a slowly growing orbital mass. Magnetic resonance imaging (MRI) revealed a well-defined orbital mass without intracranial extension. The microscopic appearance of the complete resection specimen showed large nests of epithelioid cells with wide cytoplasm containing melanin pigment and round to oval nuclei with mild cytonuclear atypia and low mitotic activity. Immunohistochemistry was positive for HMB45 and negative for melanA, smooth muscle actin, desmin and S-100 protein. Pangenomic RNA-sequencing identified an in-frame NONO-TFE3 rearrangement, and clustering data showed that the tumor's gene expression profile was grouped with other previously studied PEComas. A diagnosis of orbital pigmented PEComa with uncertain malignant potential associated with a NONO-TFE3 rearrangement was made. There was no recurrence after 1 year of follow-up.

5.
Vascul Pharmacol ; 47(4): 209-14, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17669692

ABSTRACT

OBJECTIVES: We report in the present study the role of endothelin (ET-1) and ET-1 receptors in the sustained hypoxia-induced systemic hypertension. METHODS: Wistar rats were randomly assigned to live continuously in hypobaric hypoxia (CH rats) or normoxia (N rats). At the end of hypoxic stress exposure (5 weeks at 450 mm Hg), measurements of mean systemic arterial pressure were done. The effects of ET-1 in the presence or not of the endothelium and/or of specific ET-A inhibitors (BQ-123) or ET-B inhibitors (BQ-788), have been investigated in an isolated model of rat thoracic aorta. Finally, plasmatic ET-1 concentrations have been determined by assay procedure. RESULTS: Following five weeks of chronic hypoxic stress, CH rats presented a significant increase of mean systemic arterial pressure (N: 129.1+/-6.8 mm Hg vs CH: 152.5+/-3.4 mm Hg; P<0.05). Despite of this hypoxia-induced hypertension, ET-1 plasmatic concentration was not different between N and CH rats. Finally, CH rats presented a reduce response to ET-1 when compared to N rats. This phenomenon seems to be associated to the ET-A vascular smooth muscle cell receptors, since difference between N and CH rats was still present in endothelium denuded aortic rings in the presence or not of the specific ET-B inhibitors (BQ-788). In addition, in the presence of the specific ET-A inhibitor (BQ-123) response to ET-1 was abolished in N and CH rats to the same extent (N:-98%; CH:-99%). CONCLUSION: This work clearly suggests that, following long term exposure to hypoxia, ET-1 and ET-1 receptors are not involved in the persistence of systemic hypertension in a rat model, and that chronic exposure to severe hypoxic stress was associated with a downregulation of the ET-A receptors response to ET-1.


Subject(s)
Aorta, Thoracic/physiology , Hypertension/etiology , Hypoxia/complications , Muscle, Smooth, Vascular/physiology , Receptor, Endothelin A/physiology , Receptor, Endothelin B/physiology , Vasoconstriction , Animals , Endothelin-1/blood , In Vitro Techniques , Male , Oligopeptides/pharmacology , Peptides, Cyclic/pharmacology , Piperidines/pharmacology , Rats , Rats, Wistar
6.
Cell Signal ; 11(3): 159-64, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10353689

ABSTRACT

Human parathyroid hormone, hPTH-(1-34), stimulates adenylyl cyclase and phosphatidylinositol-bisphosphate-specific phospholipase-C (PIP2-PLC), as indicated by increased membrane-associated protein kinase C (PKC) activity in ROS 17/2 rat osteosarcoma cells. The C-terminally truncated hPTH-(1-31)NH2 stimulates adenylyl cyclase as strongly as hPTH-(1-34) in these cells, but it does not stimulate PKC activity. Even [Leu27]-cyclo(Glu22-Lys26)-hPTH-(1-31)NH2, a 6-fold stronger adenylyl cyclase stimulator than hPTH-(1-34), cannot stimulate PKC activity in ROS cells. Therefore PTH required its 32-34 region to stimulate PIP2-PLC/PKCs in this osteosarcoma line. In contrast, hPTH-(1-31)NH2 [Leu27]-cyclo(Glu22-Lys26)-hPTH-(1-31)NH2 and even hPTH-(1-30)NH2 can stimulate PKC activity in freshly isolated rat spleen lymphocytes as strongly as hPTH-(1-34)NH2. The difference in the ability of membrane-associated PKC activity in spleen lymphocytes, but not in ROS cells, to be stimulated by C-terminally truncated PTH fragments might be due to different receptor densities or to the lymphocyte's atypical PTH/PTHrP receptor.


Subject(s)
Lymphocytes/metabolism , Parathyroid Hormone/metabolism , Peptide Fragments/metabolism , Protein Kinase C/metabolism , Spleen/metabolism , Animals , Dose-Response Relationship, Drug , Female , Humans , Osteosarcoma/metabolism , Rats , Rats, Sprague-Dawley
7.
Water Res ; 39(5): 911-21, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15743638

ABSTRACT

We present results that were obtained with a newly developed fluorometer, the 'PhytoSensor'. They are based on multi-wavelength excitation of chlorophyll fluorescence to detect the phytoplankton biomass and to identify main taxons (among cyanobacteria, green and brown microalgae). A method to evaluate the photosynthetic potential of the phytoplankton was established. Attention was focused on the measurement of the cyanobacterial biomass. A modelling to distinguish between the two spectral groups (blue and red) of cyanobacteria as a function of their pigments and physiological status is proposed. The main innovation of the device results in the recording of the fluorescence induction kinetics of the phytoplankton to confirm and refine the evaluation of the taxonomic composition. The PhytoSensor abilities were compared with pigment analysis, commercial fluorometers, particle and microscopic counting and identification. The PhytoSensor has been used with success to monitor the dynamics of phytoplankton in drinking-water supply reservoirs in Southeast Asia.


Subject(s)
Chlorophyll/analysis , Cyanobacteria/metabolism , Environmental Monitoring/methods , Phytoplankton/chemistry , Asia , Azo Compounds , Cyanobacteria/chemistry , Environmental Monitoring/instrumentation , Eosine Yellowish-(YS) , Fluorescence , Kinetics , Methyl Green , Photochemistry , Time Factors , Water Supply
8.
J Bone Miner Res ; 12(8): 1246-52, 1997 Aug.
Article in English | MEDLINE | ID: mdl-9258755

ABSTRACT

Human parathyroid hormone (hPTH)-(1-31)NH2 (Ostabolin), which only stimulates adenylyl cyclase (AC) instead of AC and phospholipase-C as do hPTH(1-84) and hPTH(1-34), strongly stimulates femoral cortical and trabecular bone growth in ovariectomized (OVX) rats. Two side-chain lactams have been introduced in the hydrophilic face of the receptor-binding region of the fragment's Ser17-Val31 amphiphilic alpha-helix in an attempt to develop improved analogs for the treatment of osteoporosis. Replacing the polar Lys27 with an apolar Leu on the hydrophobic face of this alpha-helix and stabilizing the helix with a lactam between Glu22 and Lys26 produced a fragment, [Leu27]-cyclo(Glu22-Lys26)-hPTH(1-31)NH2, which had six times the AC-stimulating ability of hPTH(1-31)NH2 in ROS 17/2 rat osteosarcoma cells, but the other helix-stabilizing lactam derivative [Leu27]-cyclo(Lys26-Arg30)-hPTH(1-31)NH2 did not have a greater AC-stimulating ability than hPTH(1-31)NH2, to stimulate AC in ROS 17/2 rat osteosarcoma cells. As expected from AC stimulation being responsible for PTH's anabolic action, [Leu27]-cyclo(Glu22-Lys26)-hPTH(1-31)NH2 was, depending on the experimental design, a 1.4 to 2 times better stimulator of trabecular bone growth in the OVX rat model than either hPTH(1-31)NH2 or [Leu27]-cyclo(Lys26-Arg30)-hPTH(1-31)NH2. Thus, there is now a more potently anabolic derivative of hPTH(1-31)NH2, [Leu27]-cyclo(Glu22-Lys26)-hPTH(1-31)NH2, which might ultimately prove to be one of the more effective therapeutics for osteoporosis.


Subject(s)
Bone Development/drug effects , Femur/drug effects , Lactams/chemistry , Osteoporosis, Postmenopausal/drug therapy , Parathyroid Hormone/pharmacology , Peptide Fragments/pharmacology , Adenylyl Cyclases/metabolism , Analysis of Variance , Animals , Bone Neoplasms/pathology , Disease Models, Animal , Female , Femur/physiology , Humans , Molecular Weight , Osteoporosis, Postmenopausal/prevention & control , Osteosarcoma/pathology , Ovariectomy , Parathyroid Hormone/chemistry , Parathyroid Hormone/therapeutic use , Peptide Fragments/chemical synthesis , Peptide Fragments/chemistry , Peptide Fragments/therapeutic use , Rats , Serine/metabolism , Structure-Activity Relationship , Tumor Cells, Cultured , Valine/metabolism
9.
J Bone Miner Res ; 15(5): 964-70, 2000 May.
Article in English | MEDLINE | ID: mdl-10804028

ABSTRACT

Human parathyroid hormone (1-28)NH2 [hPTH(1-28)NH2] is the smallest of the PTH fragments that can fully stimulate adenylyl cyclase in ROS 17/2 rat osteoblast-like osteosarcoma cells. This fragment has an IC50 of 110 nM for displacing 125I-[Nle8,18,Tyr34]bovine PTH(1-34)NH2 from HKRK B7 porcine kidney cells, which stably express 950,000 human type 1 PTH/PTH-related protein (PTHrP) receptors (PTH1Rs) per cell. It also has an EC50 of 23.9 nM for stimulating adenylyl cyclase in ROS 17/2 cells. Increasing the amphiphilicity of the alpha-helix in the residue 17-28 region by replacing Lys27 with Leu and stabilizing the helix by forming a lactam between Glu22 and Lys26 to produce the [Leu27]cyclo(Glu22-Lys26)hPTH(1-28)NH2 analog dramatically reduced the IC50 for displacing 125I-[Nle8,18,Tyr34]bPTH(1-34)NH2 from hPTH1Rs from 110 to 6 nM and dropped the EC50 for adenylyl cyclase stimulation in ROS 17/2 cells from 23.9 to 9.6 nM. These modifications also increased the osteogenic potency of hPTH(1-28)NH2. Thus, hPTH(1-28)NH2 did not significantly stimulate either femoral or vertebral trabecular bone growth in rats when injected daily at a dose of 5 nmol/100 g body weight for 6 weeks, beginning 2 weeks after ovariectomy (OVX), but it strongly stimulated the growth of trabeculae in the cancellous bone of the distal femurs and L5 vertebrae when injected at 25 nmol/100 g body weight. By contrast [Leu27]cyclo(Glu22-Lys26)hPTH(1-28)NH2 significantly stimulated trabecular bone growth when injected at 5 nmol/100 g of body weight. Thus, these modifications have brought the bone anabolic potency of hPTH(1-28)NH2 considerably closer to the potencies of the larger PTH peptides and analogs.


Subject(s)
Adenylyl Cyclases/metabolism , Bone Development/drug effects , Lactams/metabolism , Peptide Fragments/pharmacology , Receptors, Parathyroid Hormone/metabolism , Teriparatide/analogs & derivatives , Animals , Cell Line , Enzyme Activation , Humans , Protein Binding , Rats , Rats, Sprague-Dawley , Swine , Teriparatide/pharmacology
10.
J Clin Endocrinol Metab ; 82(10): 3383-8, 1997 Oct.
Article in English | MEDLINE | ID: mdl-9329373

ABSTRACT

Enzymatic activity and isoform expression of cathepsin D (cath D) were studied in 107 cytosols from various human thyroid tissues including 21 normal tissues, 12 cold benign nodules, 17 toxic adenomas, 22 samples from Graves' disease patients, and 35 thyroid carcinomas. Cath D assay was optimized for human thyroid tissues. We found that mean cath D specific activities, expressed as units per milligrams protein minus thyroglobulin, were higher in carcinomas (P = 0.0001), toxic adenomas (P = 0.0001), and specimens from Graves' disease patients (P = 0.0001) than in normal thyroid tissues. Mean cath D activity in carcinomas was also significantly different from that in cold benign nodules (P < 0.001) and Graves' disease tissues (P < 0.05) but not from that of toxic adenomas. To determine possible mechanisms by which the observed increase in cath D activity might be regulated, we used Western blotting to measure relative amounts of cath D isoforms in the various thyroid tissues. We found that the 31-kDa major processing form of cath D was significantly increased in carcinomas and toxic adenomas compared with normal tissues (P < 0.01), cold benign nodules (P < 0.05), and Graves' disease tissues (P < 0.05). A positive correlation of cath D activity with relative expression of the 31-kDa form (r = 0.67, P = 0.0001) was observed in 104 thyroid cytosols. These data demonstrate a deregulation at the protein level, with resulting increases in cath D activity. Immunogold labeling of cath D showed particle concentration in lysosomes or phagosomes in both normal follicles and papillary carcinoma cells, indicating that cath D localization was not altered by malignant transformation in human thyroid cells. TSH induced cath D synthesis and secretion in extracellular fluid of normal human thyroid cells in primary culture; TSH had little effect on intracellular cath D level. In conclusion, TSH-induced cath D synthesis may explain high cath D levels in Graves' disease tissues and toxic adenomas, because these tissues possess a permanently stimulated cAMP transduction pathway. Furthermore, the overexpression of cath D in thyroid carcinomas in comparison with normal controls adds further arguments for the potential role of cath D in tumor growth and metastasis.


Subject(s)
Cathepsin D/metabolism , Thyroid Gland/drug effects , Thyroid Gland/metabolism , Thyrotropin/pharmacology , Adult , Aged , Cells, Cultured , Female , Humans , Immunoblotting , Immunohistochemistry , Isoenzymes/metabolism , Male , Middle Aged , Reference Values , Thyroid Diseases/metabolism , Thyroid Gland/cytology , Tissue Distribution
11.
J Med Chem ; 40(9): 1373-80, 1997 Apr 25.
Article in English | MEDLINE | ID: mdl-9135034

ABSTRACT

In a search for analogues of human parathyroid hormone (hPTH) with improved activities and bioavailabilities, we have prepared the following three lactam analogues of hPTH-(1-31)-NH2 (1) or [Leu27]hPTH-(1-31)-NH2 (2): [Leu27]cyclo(Glu22-Lys26)-hPTH-(1-31)-NH2 (3), [Leu27]cyclo(Lys26-Asp30)-hPTH-(1-31)-NH2 (4), and cyclo(Lys27-Asp30)-hPTH-(1-31)-NH2 (5). Analogues 1, 2, and 5 had seven or eight residues of alpha-helix, as estimated from their circular dichroism (CD) spectra, in contrast to 12 residues in cyclic analogues 3 and 4. Thus, lactams 3 and 4 stabilized a helix previously shown to exist within residues 17-29. The adenylyl cyclase activity (EC50), measured in rat osteosarcoma 17/2 cells, of 5 (40.3 +/- 2.3 nM) was half that of its linear form 1 (19.9 +/- 3.9 nM). The linear Leu27 mutant 2 was twice as active (11.5 +/- 5.2) as analogue 1, and lactam analogue 3 was 6-fold more active (3.3 +/- 0.3 nM). Lactam analogue 4 had less activity (16.9 +/- 3.3 nM) than 2, its linear form. Peptides hPTH-(1-30)-NH2 (6), [Leu27]hPTH-(1-30)-NH2 (7), and [Leu27]cyclo(Glu22-Lys26)-hPTH-(1-30)-NH2 (8) all had AC-stimulating activities similar to that of 1. When injected intravenously, with a dose of 0.8 nmol/100 g of analogue in acid saline, hypotensive effects paralleled their adenylyl cyclase activities. They behaved quite differently when applied subcutaneously. Analogues 1, 5, and 6, the weakest, showed about half the drop in blood pressure observed with 3 and 4, the most active. In contrast, the time required to reach a maximum drop in blood pressure of 4-8, after subcutaneous administration, was 2-4 times that of the other analogues. Thus, the bioavailabilities of the lactam analogues, unlike their adenylyl cyclase-stimulating activities, were highly dependent on the presence or conformation of Val31.


Subject(s)
Adenylyl Cyclases/metabolism , Antihypertensive Agents/chemistry , Lactams/chemistry , Parathyroid Hormone/chemistry , Receptors, Parathyroid Hormone/metabolism , Amino Acid Sequence , Amino Acids/analysis , Animals , Antihypertensive Agents/chemical synthesis , Antihypertensive Agents/metabolism , Antihypertensive Agents/pharmacology , Blood Pressure/drug effects , Circular Dichroism , Enzyme Activation , Humans , Lactams/chemical synthesis , Lactams/metabolism , Lactams/pharmacology , Models, Molecular , Molecular Sequence Data , Osteoblasts/enzymology , Parathyroid Hormone/metabolism , Parathyroid Hormone/pharmacology , Peptide Fragments/chemical synthesis , Peptide Fragments/pharmacology , Protein Conformation , Protein Structure, Secondary , Rats , Tumor Cells, Cultured
12.
Biotechnol Adv ; 2(2): 201-16, 1984.
Article in English | MEDLINE | ID: mdl-14545696

ABSTRACT

New gene selection techniques (Recombinant DNA) are currently available to exploit useful properties of various biological systems hitherto regarded as interesting but of little or no immediate commercial value. The application of genetic engineering techniques to problems in the Pulp and Paper Industry are many. As a first step these techniques are being used to provide much needed fundamental information on the cellular and molecular mechanisms involved in the expression of extra-cellular enzymes that degrade lignocellulosic pulping wastes. The information gleaned from the studies on cellulolytic fungi and bacteria can be used to genetically engineer a yeast or bacterium capable of converting pulping wastes into ethanol and other useful by-products.

13.
Biochem Pharmacol ; 43(7): 1507-11, 1992 Apr 01.
Article in English | MEDLINE | ID: mdl-1314603

ABSTRACT

We studied the effect of bromolevamisole (BL) and other imidazo [2,1-b] thiazole derivatives--bromodexamisole (BD) and levamisole (LV)--on adenylate cyclase (AC) activity. BL and BD both inhibited forskolin-activated human thyroid AC, while LV had no effect. This inhibition was non-stereospecific and the IC50 values, as measured with 1 mM ATP and 40 microM forskolin, were 0.95 and 0.80 mM for BL and BD, respectively. In contrast, human thyroid alkaline phosphatase (ALP) inhibition was stereospecific, with IC50 values of 0.0012 mM for BL and 0.9 mM for BD. LV was a 10-fold weaker inhibitor of ALP than BL. These results show that ALP inhibition is not correlated with forskolin-activated AC inhibition. Furthermore, in the presence of a competitive inhibitor of GTP (0.1 mM guanosine 5'-O-(2-thiodiphosphate), BL retained its antagonizing effect on forskolin-activated AC which suggests a direct action on the catalytic subunit. The inhibition was of the mixed type, indicating a complex interaction between BL and AC. Glucagon-activated AC activity in rat liver membranes was also inhibited by BL, although to a slightly lesser degree than thyroid stimulating hormone (TSH)-activated AC from human thyroid for a given BL concentration. In cultured human thyroid cells, BL (0.25 mM) induced a potent decrease in cAMP accumulation after 2 hr of stimulation by TSH. Taken together, these results show that BL inhibits AC and that this inhibition is not organ-specific.


Subject(s)
Adenylyl Cyclase Inhibitors , Levamisole/pharmacology , Tetramisole/analogs & derivatives , Alkaline Phosphatase/antagonists & inhibitors , Animals , Binding Sites/drug effects , Cell Membrane/drug effects , Cell Membrane/enzymology , Colforsin/pharmacology , Cyclic AMP/metabolism , Enzyme Activation/drug effects , Humans , Kinetics , Liver/drug effects , Liver/enzymology , Rats , Tetramisole/pharmacology , Thyroid Gland/drug effects , Thyroid Gland/enzymology
14.
Eur J Endocrinol ; 141(1): 70-4, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10407226

ABSTRACT

OBJECTIVE: Daily injections of human parathyroid hormone (hPTH) increase bone volume in various animal species and in osteoporotic women. For hPTH to be widely accepted as an anabolic therapy for treating postmenopausal osteoporosis alternative delivery options need to be explored to replace the need for daily patient subcutaneous self-injection. Among these are inhalation, oral delivery and the use of programmable implanted minipumps to deliver the peptide. While infusion of high doses of PTH causes bone loss and hypercalcemia, no studies have assessed the effects of prolonged infusion of low doses of PTH on bone growth. DESIGN AND METHODS: [Leu(27)]-cyclo(Glu(22)-Lys(26))-hPTH-(1--31)NH(2) was delivered by Alzet minipumps to ovariectomized rats for 6 weeks after which histomorphometric indices (cancellous bone volume, trabecular thickness, mean trabecular number) of bone formation were measured in distal femurs. RESULTS: Infusing low doses (0.05 and 0.1 nmole/100g body weight/day) of the hPTH analog, [Leu(27)]-cyclo(Glu(22)-Lys(26))-hPTH-(1--31)NH(2), for 6 weeks does not prevent the ovariectomy-induced loss of rat femoral cancellous bone volume, trabecular thickness or trabecular number. CONCLUSION: These results support the absolute requirement of daily injections for the osteogenic action of hPTH on bone.


Subject(s)
Bone and Bones/drug effects , Osteoporosis/prevention & control , Ovariectomy , Parathyroid Hormone/administration & dosage , Peptide Fragments/administration & dosage , Animals , Bone Density , Female , Femur , Humans , Rats , Rats, Sprague-Dawley
15.
Surgery ; 111(1): 114-7, 1992 Jan.
Article in English | MEDLINE | ID: mdl-1728067

ABSTRACT

Adrenal myelolipomas are rare, nonfunctioning benign tumors that consist of mature fat and bone-marrow elements. In the first half of this century, most adrenal myelolipomas were found incidentally at autopsy. These tumors are usually unilateral and asymptomatic. Today they are detected by ultrasonography, computerized tomography, or magnetic resonance imaging scan, done for other reasons. Adrenal myelolipomas can be diagnosed because of their characteristic images. Thus they are classified as "incidentalomas." We report the case of a 50-year-old man who had bilateral adrenal myelolipomas and whose right-side tumor was symptomatic. To our knowledge it is the third operated case reported in the literature. A right adrenalectomy was performed, keeping the asymptomatic left adrenal myelolipoma to preserve adrenal function.


Subject(s)
Adrenal Gland Neoplasms/surgery , Lipoma/surgery , Adrenal Gland Neoplasms/diagnosis , Humans , Lipoma/diagnosis , Male , Middle Aged
16.
Surgery ; 118(6): 1036-40, 1995 Dec.
Article in English | MEDLINE | ID: mdl-7491520

ABSTRACT

BACKGROUND: Cathepsin D is a widely distributed lysosomal acidic endopeptidase. It is an estrogen-regulated protein that is a prognostic factor in breast cancer. The aim of this study was to measure cathepsin D concentrations in thyroid tissues and to correlate these concentrations with clinical and pathologic parameters. METHODS: Cathepsin D and thyroglobulin concentrations were measured in the cytosol of normal thyroid tissues (n = 14), benign nodules (n = 6), and thyroid carcinomas (n = 32) with an immunoradiometric assay. Statistical analysis was based on the Kruskal-Wallis and Wilcoxon tests and on the Spearman rank correlation coefficient. RESULTS: The mean level of cathepsin D, expressed as picomoles per milligram protein minus thyroglobulin, was higher in the 32 carcinomas, 29.1 +/- 15.5, than in the 14 normal thyroid tissues, 8.4 +/- 2.5 (p < 0.001) or in the 6 benign nodules, 11.2 +/- 7.3 (p = 0.003). Cathepsin D concentrations correlated with tumor size; Spearman rank correlation coefficient was rs = 0.44 (p = 0.012). No significant difference was found regarding histologic type. Cathepsin D concentrations were inversely correlated with the thyroglobulin level in the tumor; Spearman rank correlation coefficient was rs = -0.60 (p < 0.001). CONCLUSIONS: Cathepsin D concentration is higher in thyroid carcinoma than in normal thyroid tissue. Increased cathepsin D concentrations correlate with thyroid tumor size but not with histologic type. Further studies should be done to confirm the potential prognostic value of cathepsin D in patients with thyroid carcinomas.


Subject(s)
Cathepsin D/analysis , Thyroid Gland/chemistry , Thyroid Neoplasms/chemistry , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Reference Values , Thyroglobulin/analysis , Thyroid Neoplasms/pathology
17.
Surgery ; 126(6): 1188-94, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10598206

ABSTRACT

BACKGROUND: Familial nonmedullary thyroid carcinoma (FNMTC) is a clinical entity characterized by a more aggressive phenotype than the sporadic counterpart. The transmission of susceptibility of FNMTC is compatible with autosomal dominant inheritance. We report the identification of a new entity of FNMTC and the mapping of the responsible gene named TCO (for thyroid tumor with cell oxyphilia). METHODS: In one family, multinodular goiters were diagnosed in six individuals and papillary thyroid carcinoma was diagnosed in three. Eight patients were operated on. Blood samples were collected from the nine affected patients and from eight unaffected relatives. The gene was mapped by linkage analysis with a whole-genome panel of microsatellite markers. RESULTS: The neoplastic cells from all lesions showed characteristic faint to marked cytoplasmic oxyphilia. We found a logarithm of odd ratio (LOD) score of 2.41 at theta = 0 for marker D19S586. Additional markers were typed in the region and were found to be in linkage, with LOD scores peaking at markers D19S916 (Zmax = 3.01 at theta = 0) and D19S413 (Zmax = 2.95 at theta = 0). All these markers have been physically mapped to 19p13.2. CONCLUSIONS: TCO was mapped to chromosome 19p13.2. Interestingly, both the benign and malignant thyroid tumors in this family exhibit some degree of oxyphilia, which has not been described until now in the familial forms of NMTC.


Subject(s)
Adenoma, Oxyphilic/genetics , Chromosome Mapping , Chromosomes, Human, Pair 19 , Proto-Oncogene Proteins c-jun/genetics , Thyroid Neoplasms/genetics , Adolescent , Adult , Carcinoma, Papillary/genetics , Child , DNA Primers , Family Health , Female , Genetic Linkage , Genetic Markers , Genotype , Haplotypes , Humans , Male , Middle Aged , Pedigree
18.
Thyroid ; 6(1): 17-21, 1996 Feb.
Article in English | MEDLINE | ID: mdl-8777379

ABSTRACT

After thyroidectomy, the anesthesiologist usually performs a laryngoscopy to detect laryngeal edema and nerve palsies. The goal of this study was to compare three different methods of laryngeal examination after tracheal extubation of the patients. For that purpose, between 1990 and 1995, a prospective series of 1608 patients operated for thyroidectomy has been studied. The series was divided into 4 groups. In group I (n = 200), four anesthesiologists have evaluated the efficiency of the immediate postextubation direct laryngoscopy. In group II (n = 100), one anesthesiologist has compared the direct, indirect, and flexible laryngoscopies in every patient in a fixed and timed fashion. In group III (n = 100), the four examiners have evaluated the flexible laryngoscopy at a different timing so as to eliminate the possible temporal relationship of the ease of visualization in group II. In group IV (n = 1208), the four examiners have evaluated flexible laryngoscopy, on a large scale, at any time during the 1-h stay in the recovery room. Special attention was directed to the patients with known cardiovascular diseases. Direct and indirect laryngoscopies were only effective in 76 and 73%, respectively, of the patients, whereas flexible laryngoscopy was effective in 99.6% of them. Flexible laryngoscopy was easy to perform in 96.5% of the patients versus 65 and 55% with direct and indirect laryngoscopies. Finally, variations in monitored cardiovascular parameters were significantly lower with flexible and indirect laryngoscopies than with direct laryngoscopy. These mild variations induced by flexible laryngoscopy were well tolerated by patients with known cardiovascular diseases. Flexible laryngoscopy is the best method for an immediate laryngoscopic examination after thyroidectomy.


Subject(s)
Laryngoscopy , Postoperative Complications/diagnosis , Thyroidectomy/adverse effects , Vocal Cord Paralysis/diagnosis , Fiber Optic Technology , Humans , Laryngoscopes , Laryngoscopy/adverse effects , Prospective Studies , Vocal Cord Paralysis/etiology
20.
Eur J Gastroenterol Hepatol ; 9(12): 1197-203, 1997 Dec.
Article in English | MEDLINE | ID: mdl-9471026

ABSTRACT

BACKGROUND AND OBJECTIVES: Little is known of the in-situ expression of adhesion molecules in ulcerative colitis (UC) according to disease activity. In the present study we investigate the vascular expression of endothelial leucocyte adhesion molecule 1 (ELAM-1/E-selectin), vascular cell adhesion molecule (VCAM-1) and intercellular adhesion molecules (ICAM-1 and ICAM-3) on the rectal mucosa of patients with UC in order to identify links between in-situ expression of these adhesion molecules and clinical, endoscopic and histological parameters. DESIGN AND METHODS: At inclusion, 16 untreated patients with UC at different stages of disease activity were assessed clinically and endoscopically and underwent rectal biopsy. Ten patients had similar assessments during follow-up. Quantitative histological and immunohistochemical scores were established with anti-E-selectin, VCAM-1, ICAM-1, ICAM-3 and HLA-DR monoclonal antibodies on frozen biopsy specimens. RESULTS: (1) At inclusion, E-selectin in-situ expression correlated with clinical activity (r = 0.7, P = 0.05), endoscopic severity (r = 0.74, P = 0.04), the histological score (r = 0.57, P = 0.02) and in-situ expression of HLA-DR on epithelial cells (r = 0.74, P = 0.01). (2) After remission, there was a significant decrease in ELAM-1 in-situ expression (P = 0.04). (3) In patients with clinical, endoscopic and histological remission the level of residual E-selectin expression appeared to be predictive of clinical relapse. (4) Vascular expression of VCAM-1 and ICAM-1 did not correlate with clinical, endoscopic or histological parameters, or with changes in disease activity. (5) ICAM-3 was never detected on endothelial cells of the colonic mucosa of controls or patients with UC. CONCLUSION: In ulcerative colitis, E-selectin, but not VCAM-1, ICAM-1 or ICAM-3, appears to play a central role in leucocyte migration into the colonic mucosa. Elevated vascular expression of E-selectin after remission may be involved in clinical recurrence.


Subject(s)
Antigens, CD , Antigens, Differentiation , Cell Adhesion Molecules/metabolism , Colitis, Ulcerative/metabolism , E-Selectin/metabolism , Adult , Aged , Anti-Inflammatory Agents/therapeutic use , Colitis, Ulcerative/drug therapy , Female , Humans , Immunohistochemistry , Intercellular Adhesion Molecule-1/metabolism , Intestinal Mucosa/drug effects , Intestinal Mucosa/metabolism , Male , Middle Aged , Prospective Studies , Rectum/drug effects , Rectum/metabolism , Vascular Cell Adhesion Molecule-1/metabolism
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