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T J Yoo

Publications and source records attributed to T J Yoo.

At least 37 records · Page 2Linked to original sources
PubMed1996

Brain stem auditory-evoked potentials of mice with experimental allergic encephalomyelitis.

Experimental allergic encephalomyelitis (EAE) is an experimental model for multiple sclerosis. In order to study autoimmune retrocochlear hearing loss, we performed brain stem auditory-evoked potential (BAEP) studies on EAE mice. The EAE was induced in B10.PL and (PL/J x SJL)F1 mice. In the BAEP study, all of the peak and interpeak latencies were prolonged significantly in the diseased mice. Hearing thresholds were slightly elevated in the immunized mice during the acute phase. Inflammatory and phagocytic cell infiltration, demyelination, and V beta 8.1, 8.2 T-cell receptor-positive cells were observed in the cochlear nerves or their proximity by histologic study. It is suggested that immunologic reactions identified with EAE also occurred in the cochlear nerve, and that these reactions were responsible for the hearing problems. It appears that EAE is a useful model system for studying autoimmune insults on the neural portion of the auditory system.

Animals↗
PubMed1996

Type II collagen-induced autoimmune ear disease in mice: a preliminary report on an epitope of the type II collagen molecule that induced inner ear lesions.

To identify the epitope on the type II collagen molecule that induced autoimmune ear disease, electrophysiological and histological studies were carried out in DBA/1J mice immunized with native chick type II collagen (Clln) and cyanogen bromide (CNBr) peptide 1I (CB-I1 peptide) that was cleaved from chicken type II collagen with CNBr digestion. Four months after immunization, three of six Clln-immunized mice and five of six CB-I1 peptide-immunized mice developed moderate hearing loss. No control animals showed hearing loss. The pattern of hearing loss was characteristic of progressive deafness. Furthermore, the immunized mice showed temporal lesions involving atrophy of the Corti organ and degeneration of the spiral ganglion, in proportion to the level of the hearing loss. Because similar inner ear lesions were induced by immunization with Clln and CB-I1 peptide, CB-I1 peptide contains at least one epitope that induces autoimmune inner ear disease in collagen II-induced disease on the chick type II collagen molecule involved in pathogenesis of autoimmune ear disease. CB-I1 peptides were concluded to contain the epitope that induces autoimmune inner ear disease in collagen IIn-induced disease.

Animals↗
PubMed1994

Epitope specificity and T cell receptor usage in type II collagen induced autoimmune ear disease.

An immune response directed against type II collagen (CII) has been reported in several autoimmune diseases including the animal models of collagen-induced arthritis (CIA) and collagen-induced autoimmune ear disease (CIAED). In this communication, we have found that T cells from type II collagen-immunized DBA/1-lac could transfer auricular chondritis to naive mice. The T cells from type II collagen-immunized H-2r and H-2q mice recognize different epitopes from the CB11 peptide of CII. The CII-specific T cells from H-2q background mice recognize peptide residues p121-147 (P1) but do not respond to residues p211-247 (P2). The T cells of H-2r mice immunized with CII respond better to P2 rather than P1. By altering certain amino acids within these epitopes, the response of CII-specific TCR to antigen has been increased or abolished. Our results suggest that the lysine residues at positions 129, 141, and 147 in P1, the arginine residue at position 227, and glutamic acid at position 230 in P2 might play an important role in the trimolecular interaction. Ten clonally distinct T cell hybridomas specific for CII have been established from H-2r B10.RIII mice and the beta chains of their TCR have been analyzed. Three subfamilies, V beta 1, V beta 6, and V beta 8, were utilized with dominant expression of V beta 8 (60%). This is quite similar to the pattern found in type II collagen-induced arthritis in H-2q mice. This preferential use of V beta 8 in CIAED implies that an immunotherapy may make it possible to control this autoimmune disease, even in a MHC-diverse situation.

Amino Acid Sequence↗
PubMed1994

Structural analysis of the mouse T-cell receptor Tcra V2 subfamily.

Cosmid clones containing T-cell receptor Tcra V2 subfamily gene segments have been isolated from a BALB/c cosmid library and subjected to DNA sequence analysis. The V gene segments in the Tcra V2 subfamily differ from each other by 3%-7% at the nucleotide level and 5%-16% at the amino acid level. T-cell receptor Tcra V2 gene segment polymorphisms have been identified in the B10.PL and PL/J mouse strains with a Tcra V2 subfamily-specific probe. These V gene segment polymorphisms may cause the differential Tcra V gene usage in induced experimental allergic encephalomyelitis between B10.PL and PL/J mice.

Amino Acid Sequence↗
PubMed1994

Immunologic analysis of anaphylaxis to protamine component in neutral protamine Hagedorn human insulin.

We report the clinical and immunologic analysis of two patients with diabetes who had anaphylaxis to neutral protamine Hagedorn (NPH) human insulin in the absence of allergy to regular insulin. A 36-year-old woman without a recent history of local insulin reactions or interruption of insulin therapy experienced anaphylaxis within 15 minutes of her usual morning dose of subcutaneously administered NPH human insulin. A 62-year-old man with a history of generalized reactions to NPH human insulin and of anaphylaxis to intravenously administered protamine had generalized urticaria after injection of NPH human insulin. Both patients subsequently tolerated Lente human insulin. Skin test results in both patients were negative to regular and Lente insulin preparations but positive to NPH insulin and to protamine at concentrations tested. In vitro assays demonstrated that both patients had markedly elevated serum levels of IgE and IgG to protamine, but not to regular human insulin, and that their IgE antibodies to protamine recognized protamine antigenic determinants in NPH human insulin. We conclude that the anaphylactic reactions to NPH insulin in our patients were mediated by IgE to protamine, which should be a pathogenetic consideration in the evaluation of immediate-type reactions to protamine-containing insulins.

Adult↗
PubMed1994

Expression and localization of COL2A1 mRNA and type II collagen in human fetal cochlea.

The expression and localization of COL2A1 mRNA and protein was examined in human fetal cochlea to study the role of this gene in hearing and to begin to understand the pathogenesis of mutations in COL2A1 in hearing disorders. Northern blot analysis revealed COL2A1 expression in fetal membranous cochlea to be markedly greater than that in fetal skin, kidney, cartilage, eye and brain. In situ hybridization revealed COL2A1 expression in marrow cells, osteoblasts, fibroblasts and some osteocytes, in addition to chondrocytes in otic capsule. In the membranous cochlea, connective tissue elements (spiral ligament, spiral limbus and modiolar connective tissue), neuronal cells, secretory cells (stria vascularis) and organ of Corti cells (sensory hair cells) were found to express COL2A1. Immunohistochemistry was performed to assess distribution of type II collagen and correlation with COL2A1 mRNA in these morphologically and functionally diverse cell populations. In otic capsule, only cartilage was found to stain positively, and in membranous cochlea, only connective tissue structures including spiral ligament, spiral limbus, tectorial and basilar membranes, modiolar and spiral lamina cartilage contained type II collagen. Nonconnective tissue cells, marrow cells and osteoblasts did not contain immunohistochemically identifiable protein. Absence of type II collagen in a subset of cochlear cells may reflect potentially either inability to detect low levels of protein in these cells or posttranscriptional regulation.

Autoradiography↗
PubMed1994

Restoration of brain stem auditory-evoked potentials by gene transfer in shiverer mice.

We studied the shiverer mouse as a model for correcting hearing disorders resulting from genetic abnormalities of the central nervous system (CNS). Shiverer mice are homozygous for an autosomal recessive mutation (deletion) in the gene for myelin basic protein (MBP), a major protein component of the myelin sheath in the CNS. Under electron microscopic observation of the cochlear nerve, the CNS portion in shiverer mice showed hypomyelination, but the peripheral portion, including spiral ganglion cells, was normal. We produced MBP-transgenic mice by microinjection of an MBP cosmid clone into the pronucleus of fertilized eggs from shiverer mice. The transgenic mice were found to recover MBP levels up to 25% of normal. A greater number of axons in the transgenic mice were myelinated than in the shiverer mice, but the myelin sheath was not as thick as in normal controls. Every interpeak latency of brain stem auditory-evoked potentials was prolonged in the shiverer mice and improved in the transgenic mice. This study provides an example of gene therapy for hearing disorders caused by a CNS abnormality. We discuss some strategies for researching genetic hearing impairment or deafness in both animals and humans.

Animals↗
PubMed1992

Electron-microscopic localization of type II, IX, and V collagen in the organ of Corti of the gerbil.

The presence of types II, IX and V collagen was probed in the organ of Corti of the adult gerbil cochlea by use of immunocytochemistry at the light- and electron-microscopic levels. Type II collagen is found in the connective tissues of the osseous spiral lamina and spiral limbus. In the region of the sensory hair cells it is present in the tectorial membrane and antibodies bind to the thick unbranched radial fibers. Type IX collagen co-localizes with type II collagen in the tectorial membrane, where antibodies bind to the thick unbranched radial fibers. Type V collagen is present in the connective tissue of the spiral limbus, the osseous spiral lamina, the eighth nerve, and the tectorial membrane. In the tectorial membrane, the staining with antibodies to type V collagen is more diffuse than that seen for types II and IX collagen and antibodies to type V bind to the thin, highly branched fibers in which the thick fibers are embedded. The results indicate that collagens characteristic of cartilage are localized in the organ of Corti. Within the tectorial membrane, types II and IX collagen form heterotypic thick fibers embedded in a reticular network of type V collagen fibers. These collagens form a highly structured matrix which contributes to the rigidity of the tectorial membrane and allow it to withstand the physical stresses associated with transmission of the stimuli necessary for sensory transduction.

Animals↗
PubMed1992

Type II and type IX collagen form heterotypic fibers in the tectorial membrane of the inner ear.

The presence of type II and IX collagen in the adult gerbil inner ear was probed by use of preembedding and post-embedding immunocytochemistry. Monoclonal antibodies to type II and IX collagen both label the tectorial membrane, an acellular structure which lies over the cochlear sensory hair cells and plays an essential role in the transduction process. At the light microscopic level, the antibodies are localized throughout the tectorial membrane. At the electron microscopic level, antibodies against types II and IX collagen are co-localized over the thick unbranched (Type A) radial fibers but not over the thin highly branched (Type B) fibers in which the thick fibers are embedded. Thus, the tectorial membrane of the cochlea represents another non-cartilaginous structure in which type II and IX collagen are present and arranged in heterotypic fibers. The organization of these fibers into bundles, meshworks and layers results in the formation of a structure with the unique properties necessary to withstand mechanical stresses associated with sensory transduction.

Animals↗
PubMed1992

Antibodies against a 30 kilodalton cochlear protein and type II and IX collagens in the serum of patients with inner ear diseases.

Collagen molecules are major extracellular matrix proteins involved in the development and support of delicate auditory sensory organs. Type II collagen is widely distributed within inner ear tissues, while type IX is found only within the labyrinthine membrane and dense fibers of the tectorial membrane. Antibody specific for type II collagen has been shown to be elevated in some patients with hearing loss due to several presumably autoimmune illnesses (including Meniere's disease, otosclerosis, chronic progressive sensorineural hearing loss, and relapsing polychondritis). Purified human type II and IX collagens and an extract of human cochlear tissue were subjected to isolation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and transferred to nitrocellulose. The sera of 21 patients with inner ear disease were examined for the presence of anticollagen and anticochlear antibodies; the sera were used to probe Western blots of purified human collagens II, IX, and XI, and cochlear protein extract with peroxidase-conjugated goat anti human polyvalent immunoglobulin as the second antibody. Anti-type II collagen antibodies were seen in 12 of 21 (57%) patients, while 13 of 21 (62%) had anti-type IX antibodies detectable by Western blot. A previously unreported 30 kd (probably noncollagen) protein was 21 (62%) had anti-type IX antibodies detectable by Western blot. A previously unreported 30 kd (probably noncollagen) protein was found by SDS-PAGE of human cochlear tissue extracts, with 3 patients, all with Meniere's disease, having antibody activity to this protein detected by Western blot.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Western↗
PubMed1992

Localization of type II, IX and V collagen in the inner ear.

Types II and IX collagen are traditionally considered cartilage collagens; however, within the inner ear, types II and IX collagen have a more diverse distribution. In the adult gerbil, type II collagen is the major fibrillar component. In the otic capsule it is present surrounding the osteocytes embedded and branching in the periosteal layer, in the cartilaginous rests of the enchondral layer, and in the endosteal layer bordering the membranous labyrinth. In the regions of the sensory cells, type II collagen is found in the osseous spiral lamina, the connective tissue of the spiral limbus, the subepithelial tissue of the maculae in the vestibule and the cristae in the ampullae, and in the spiral ligament. It is present in the non-cartilaginous and acellular structures of the tectorial membrane over the cochlear hair cells and the vestibular membrane lining the semicircular canals. Type IX collagen, when present, in all cases co-localizes with type II collagen but is found in more limited regions. It is found only in the cartilaginous rests of the enchondral bone, the tectorial membrane and the vestibular membrane. Type V-like collagen, a connective tissue collagen, is found to have a complementary localization to types II and IX collagen within the interstitial bone of the otic capsule, the osseous spiral lamina and the tectorial membrane, but it is absent from the vestibular membrane. This report is the first documenting the co-localization of types II and IX collagen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Activation mechanisms of platelet-activating factor in U937 cells: possible involvement of protein kinase C.

We have previously demonstrated that platelet-activating factor (PAF) binds specifically on cell membranes isolated from U937 cells. We now describe biological evidence showing that the effect of PAF on U937 cells is a receptor-mediated event. myo-[3H]Inositol-labeled U937 cells were used to investigate the possible role of phosphoinositide metabolism in these cells after binding of PAF. Formation of inositol phosphates (IP1, IP2, and IP3) in response to PAF was increased two- to threefold more than in vehicle control in U937 cells. The effect of PAF on endogenous protein phosphorylation was also studied by using 32PO4-labeled cells. PAF stimulates the phosphorylation of a 45-kDa protein in a time-dependent and dose-related fashion. Since the phospholipase C-generated diglyceride is an important activator of protein kinase C, the phosphorylated 45-kDa protein could be the substrate of protein kinase C. In this regard, we were able to demonstrate that phorbol ester enhances the phosphorylation of the same 45-kDa protein band. In addition, sphingosine, a protein kinase C inhibitor, inhibits the phosphorylation of the same 45-kDa protein band. Down-regulation of the protein kinase C also inhibits the 45-kDa protein phosphorylation. These results suggest that protein kinase C is involved in the PAF-U937 cell interaction.

Diglycerides↗
PubMed1991

Ultrastructural changes of cochlea in mice with hereditary chondrodysplasia (cho/cho).

Chondrodysplasia (cho/cho) is a recessive disorder in mice that affects cartilage important in the embryogenesis of cochlea. These mice show marked hearing loss when tested by auditory brain-stem responses. The temporal bone shows underdevelopment of the organs of Corti in the lower turn of the cochlea. Also, there are no supporting cells, inner or outer hair cells, nerve endings, or pillar cells. At the upper part of the cochlea, however, the organ of Corti is almost normal in structure. The exact nature of the molecular genetic abnormality that gives rise to the structural and functional cochlear anomalies seen in these mice is unknown.

Animals↗
PubMed1991

The molecular and structural basis of hearing impairment in mice with the cpk mutant gene.

We studied hearing impairment and cochlear ultrastructure in C57BL/6J mice containing the cpk mutant gene. Heterozygous cpk/+ mutant mice, 6-8 months old, showed a marked hearing loss as demonstrated by auditory evoked potentials with some showing hearing loss at 90 db sound pressure. Ultrastructural studies of first cochlear turn disclosed the absence of organs of Corti, no tissues on the basilar membrane, scanty spiral ganglia, normal tectorial membrane, and vacuolation of the stria vascularis. Reissner's membrane is normal at the endolymphatic side, but transparent at the perilymphatic side. In the second turn the organ of Corti are normal but Nuel's space is full of debris. The cpk mutant mice have hearing impairment perhaps due to deficiencies of genes expressing vital basement membrane components.

Acoustic Stimulation↗
PubMed1991

Hearing impairment in mice with the cmd/cmd (cartilage matrix deficiency) mutant gene.

Mice homozygous for the autosomal recessive gene cartilage matrix deficiency (cmd) are afflicted with lesions involving cartilaginous tissue which give rise to, among other things, marked hearing loss as evidenced by auditory evoked potentials. Ultrastructural studies of the inner ear reveal that while inner hair cells are normal in shape and content, the outer hair cells have disappeared and there is some debris in Nuel's space. The pillar cells are normal as are the stria vascularis, basilar membrane, and tectorial membrane. We conclude that the cmd gene, thought to be vital in the regulation of proteoglycan synthesis, is responsible for the hearing impairment and structural anomalies of the cochlea seen in these mutant, homozygous mice.

Animals↗
PubMed1991

Monoclonal antibodies against bovine type IX collagen (LMW fragment): production, characterization, and use for immunohistochemical localization studies.

Four high-affinity monoclonal antibodies (MAb) which react specifically with the low molecular weight (LMW) fragment of bovine type IX collagen (BIX) have been produced in mice. On the basis of the ability of these MAb to cross-react with type IX collagen purified from human, rat, and chick cartilage and to inhibit one another in a competitive inhibition assay, we conclude that the MAb D1-9, B3-1, and B2-7 recognize unique epitopes, whereas MAb B4-5 recognizes the same epitope as B3-1. None of the MAb reacted with bovine type I, II, and XI collagen. MAb D1-9 and B3-1 were tested for their ability to bind to tissue antigen, using an immunohistochemical assay system. Positive immunoperoxidase reactions were observed in the perichondrocytic regions of human and rat costochondral cartilage. Positive responses were also detected in rat auricular cartilage, as well as in tissue obtained from the middle and inner ears of rats and mice. This report demonstrates the relative ease of producing MAb to heterologous type IX collagen and the utility of these MAb for localizing type IX collagen in cartilage and cartilage-like tissues.

Animals↗