ABSTRACT
Mutation in the myocilin gene is associated with 4% (familial form) of glaucoma cases. The underlying mechanism in non-familial cases remains unclear. Myocilin is shown here to undergo a post-transcriptional modification event, giving rise to deletion forms. Data presented show the expression profile of the shorter transcripts occurs in a tissue-specific and donor-specific manner, and the possibility is raised that their expression is disease-associated. Furthermore, demonstration of their upregulation by dexamethasone provide support for a possible role in steroid-induced glaucoma, a model for the disease process of glaucoma.
Subject(s)
Eye Proteins/genetics , Glaucoma, Open-Angle/genetics , Glycoproteins/genetics , RNA Processing, Post-Transcriptional , Adolescent , Adult , Aged , Aged, 80 and over , Base Sequence , Blotting, Northern , Cell Line , Child , Child, Preschool , Ciliary Body/metabolism , Cytoskeletal Proteins , DNA, Complementary/chemistry , DNA, Complementary/genetics , Dexamethasone/pharmacology , Female , Gene Deletion , Gene Expression , Gene Expression Regulation/drug effects , Glaucoma, Open-Angle/pathology , Humans , Infant , Male , Middle Aged , RNA, Messenger/genetics , RNA, Messenger/metabolism , Retina/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Sequence Analysis, DNA , Sequence Deletion , Tissue Distribution , Trabecular Meshwork/cytology , Trabecular Meshwork/drug effects , Trabecular Meshwork/metabolism , Transcription, Genetic , Up-Regulation/drug effectsABSTRACT
OBJECTIVE: To observe the effect of anticancer polypeptide from Buthus Martensii Venom (APBMV) on Immune function in the H22-bearing mice. METHODS: The MTT colorimetric method, homolysin assay, lymphocyte transformation test, delayed hypersensitivity assay and WBC-count of peripheral blood were used in this study. RESULTS: APBMV could obviously augment NK activity, promote proliferation of lymphocytes induced by Con A, potentiate the response of DTH induced by DNCB, antagonize the decrease of WBC in peripheral blood induced by 5-Fu in the H22-bearing mice. CONCLUSION: APBMV can obviously increase immune function in the H22-bearing mice and antagonize hypoimmunity immunodeficiency or immunodeficiency induced by chemotherapy or the tumor.
Subject(s)
Antineoplastic Agents/pharmacology , Liver Neoplasms, Experimental/immunology , Materia Medica/pharmacology , Scorpion Venoms/pharmacology , Animals , Humans , Hypersensitivity, Delayed/immunology , Killer Cells, Natural/immunology , Liver Neoplasms, Experimental/pathology , Lymphocyte Activation , Male , Mice , Neoplasm Transplantation , Tumor Cells, CulturedABSTRACT
A 65-kDa protein and a 10-kDa protein are two of the more strongly immunoreactive components of Mycobacterium tuberculosis, the causative agent of tuberculosis. The 65-kDa antigen has homology with members of the GroEL or chaperonin-60 (Cpn60) family of heat shock proteins. The 10-kDa antigen has homology with the GroES or chaperonin-10 family of heat shock proteins. These two proteins are encoded by separate genes in M. tuberculosis. The studies reported here reveal that M. tuberculosis contains a second Cpn60 homolog located 98 bp downstream of the 10-kDa antigen gene. The second Cpn60 homolog (Cpn60-1) displays 61% amino acid sequence identity with the 65-kDa antigen (Cpn60-2) and 53% and 41% identity with the Escherichia coli GroEL protein and the human P60 protein, respectively. Primer-extension analysis revealed that transcription starts 29 bp upstream of the translation start of the Cpn60-1 homolog and protein purification studies indicate that the cpn60-1 gene is expressed as an approximately 60-kDa polypeptide.
Subject(s)
Antigens, Bacterial/genetics , Bacterial Proteins/genetics , Genes, Bacterial , Heat-Shock Proteins/genetics , Mycobacterium tuberculosis/genetics , Antigens, Bacterial/biosynthesis , Bacterial Proteins/biosynthesis , Bacterial Proteins/isolation & purification , Base Sequence , Chaperonin 60 , Chromatography, Affinity , DNA, Bacterial/genetics , DNA, Bacterial/isolation & purification , Gene Library , Heat-Shock Proteins/biosynthesis , Heat-Shock Proteins/isolation & purification , Molecular Sequence Data , Molecular Weight , Mycobacterium bovis/genetics , Mycobacterium tuberculosis/metabolism , Oligodeoxyribonucleotides , RNA, Bacterial/genetics , RNA, Bacterial/isolation & purification , Restriction Mapping , Sequence Homology, Amino AcidABSTRACT
This study examined the role of central adrenergic receptors in the regulation of water absorption by the rat ileum. Clonidine, an alpha 2-adrenergic receptor agonist, increased water absorption in vivo following intracerebroventricular but not intravenous injection. Intracerebroventricular injection of prazosin, an alpha 1-adrenergic receptor antagonist, did not alter basal water absorption. Prazosin did not prevent the clonidine effect. In contrast, the alpha 2-adrenergic receptor antagonist, yohimbine, reduced basal absorption and prevented the intracerebroventricular clonidine effect. Treatment with reserpine reduced ileal norepinephrine content by 98%, reduced basal water absorption consistent with a loss of sympathetic outflow to the mucosa, but did not prevent the increase in water absorption due to intracerebroventricular clonidine. These results suggest that central alpha 2 receptors regulate water absorption by the rat ileum. The clonidine-induced increase in water absorption is not mediated by the sympathetic nerves innervating the intestine.
Subject(s)
Brain/physiology , Clonidine/pharmacology , Ileum/metabolism , Receptors, Adrenergic, alpha/physiology , Water/pharmacokinetics , Absorption , Adrenergic alpha-Antagonists/pharmacology , Animals , Injections, Intraventricular , Male , Rats , Rats, Inbred Strains , Reserpine/pharmacology , SympathectomyABSTRACT
The central nervous system (CNS) regions regulating ileal water and ion absorption are unknown. We determined 1) the CNS origin of brain stem neurons that directly innervate the rat ileum, and 2) that these neurons influence intestinal water absorption. Horseradish peroxidase (HRP) was injected into the muscle layer of the rat ileum. The brains were examined for HRP reaction product (HRPRP) 3, 5, or 7 days later. Only cell bodies of the dorsal motor nucleus of the vagus (DMNV) were labeled. Unilateral cervical vagotomy prevented deposition in the ipsilateral DMNV. To determine whether the DMNV regulates ileal water absorption, electrical and chemical stimulation (30 microA, 4 Hz, 0.2 ms, and 300 pmol L-glutamate every 5 min, respectively) were used. Both the DMNV and the adjacent nucleus tractus solitarius (NTS) were stimulated, causing a reduction in water absorption. Bilateral vagotomy prevented the effect of bilateral electrical stimulation, but unilateral vagotomy did not prevent the decrease due to ipsilateral stimulation. These studies show that 1) the DMNV innervates the ileum, and 2) alteration of vagal efferent activity by stimulation of the DMNV and NTS reduces ileal water absorption.