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Biomedical subjects

Y Yoshihara

Publications and source records attributed to Y Yoshihara.

At least 19 recordsLinked to original sources
PubMed1998

Human erythrocyte bisphosphoglycerate mutase: inactivation by glycation in vivo and in vitro.

2,3-Bisphosphoglycerate mutase (BPGM) [EC 5.4.2.4] is a multifunctional enzyme that catalyzes both the synthesis and the degradation of 2,3-diphosphoglycerate (2,3-DPG) and contains three types of activities in that it functions as a 2,3-DPG synthetase, a phosphoglycerate mutase and a 2,3-DPG phosphatase. In humans, BPGM occurs only in erythrocytes and plays a pivotal role in the dissociation of oxygen from hemoglobin via 2,3-DPG. The present study shows that the specific activity of BPGM in erythrocytes of diabetic patients is decreased, compared to normal controls as judged by 2,3-DPG synthetase activity and immunoreactive contents. To understand the mechanism by which the enzyme is inactivated, the enzyme was purified from pooled erythrocytes from diabetic patients and subjected to a boronate affinity column. The flow through fraction was active while the bound fraction was completely inactive. The bound fraction was reactive to an anti-hexitollysine antibody, indicating that the enzyme had undergone glycation and inactivation. The primary glycated site of the enzyme was found to be Lys158 as judged by amino acid sequencing and the reactivity with an anti-hexitollysine IgG, after reverse-phase HPLC of the lysyl-endopeptidase-digested peptides. Extensive glycation of recombinant BPGM in vitro indicated that the glycation sites were Lys2, Lys4, Lys17, Lys42, Lys158, and Lys196. From these results, the loss of enzymatic activity appears to be due to the glycation of Lys158 which may be located in the vicinity of the substrate binding site.

Aged↗
PubMed1998

cDNA cloning and characterization of mouse nifS-like protein, m-Nfs1: mitochondrial localization of eukaryotic NifS-like proteins.

We have isolated a mouse cDNA which shows significant sequence similarity to the yeast nifS-like gene (y-NFS1), and termed it m-Nfs1. The deduced protein sequence (459 amino acids long) has several characteristic features common to those of bacterial NifS proteins, but distinct from them by its amino-terminal extension which contains a typical mitochondrial targeting presequence. m-Nfs1 was found to be a soluble 47-kDa protein in the matrix fraction of mouse liver mitochondria. The m-Nfs1 gene was ubiquitously expressed in most tissues, suggesting its housekeeping function in vivo. We also found that the gamma-NFS1 protein was localized in the mitochondrial matrix in yeast cells. These results suggest that both eukaryotic NifS-like proteins may play some roles in mitochondrial functions.

Amino Acid Sequence↗
PubMed1998

Polarized distribution and cell type-specific localization of telencephalin, an intercellular adhesion molecule.

Telencephalin is an intercellular adhesion molecule (ICAM) restricted to the telencephalon. This study demonstrates that immunolabeled telencephalin is targeted to the somatodendritic domain of cultured hippocampal pyramidal neurons beginning with the first stages of dendritic differentiation. In contrast, it is entirely excluded from all gamma-aminobutyric acid (GABA)ergic inhibitory interneurons at all stages of development. Prior to the stage at which nearly all pyramidal neurons express telencephalin, labeled neurons possess more extensive dendritic arbors than unlabeled pyramidal neurons. More synaptic boutons form with the larger, more elaborate telencephalin-expressing dendritic trees, but bouton number per unit length is similar between neurons with and without telencephalin. These findings suggest that telencephalin identifies pyramidal neurons, it may identify plasma membrane as dendritic, and it may be generally adhesive or stabilize dendritic membranes, but it is probably not specifically synaptic. Such characteristics would be expected to be important for the formation of cell type-specific dendritic arbors.

Animals↗
PubMed1998

Involvement of dendritic adhesion molecule telencephalin in hippocampal long-term potentiation.

Telencephalin (TLCN) is a cell adhesion molecule belonging to the immunoglobulin superfamily whose expression is restricted to neurons within the most highly developed brain segment, telencephalon. Immunoelectronmicroscopic study revealed that in the hippocampal CA1 region, TLCN was localized at the surface membrane of postsynaptic spines of pyramidal cell dendrites but not at that of axonal terminals. Blocking of TLCN function using anti-TLCN antibody or recombinant soluble TLCN protein caused a striking suppression of the long-term potentiation (LTP) at the Schaffer collateral-CA1 synapses. The suppression was observed even when the blocking was initiated immediately after the tetanic stimuli. These observations suggest a role for TLCN-mediated cell-cell interactions as a key step in the development of LTP.

Animals↗
PubMed1998

Nocistatin, a peptide that blocks nociceptin action in pain transmission.

Prolonged tissue damage or injury often leads to chronic pain states such that noxious stimuli evoke hyperalgesia and innocuous tactile stimuli evoke pain (allodynia). The neuropeptide nociceptin, also known as orphanin FQ, is an endogenous ligand for the orphan opioid-like receptor which induces both hyperalgesia and allodynia when administered by injection through the theca of the spinal cord into the subarachnoid space (that is, intrathecally). Here we show that the nociceptin precursor contains another biologically active peptide which we call nocistatin. Nocistatin blocks nociceptin-induced allodynia and hyperalgesia, and attenuates pain evoked by prostaglandin E2. It is the carboxy-terminal hexapeptide of nocistatin (Glu-Gln-Lys-Gln-Leu-Gln), which is conserved in bovine, human and murine species, that possesses allodynia-blocking activity. We have also isolated endogenous nocistatin from bovine brain. Furthermore, intrathecal pretreatment with anti-nocistatin antibody decreases the threshold for nociceptin-induced allodynia. Although nocistatin does not bind to the nociceptin receptor, it binds to the membrane of mouse brain and of spinal cord with high affinity. Our results show that nocistatin is a new biologically active peptide produced from the same precursor as nociceptin and indicate that these two peptides may play opposite roles in pain transmission.

Amino Acid Sequence↗
PubMed1998

Dendrite-associated cell adhesion molecule, telencephalin, promotes neurite outgrowth in mouse embryo.

Telencephalin (TLCN) is a dendrite-associated cell adhesion molecule expressed by neurons within the telencephalon. It belongs to the intercellular adhesion molecule subgroup of the immunoglobulin superfamily. To examine a neurite outgrowth-promoting activity, neurons dissociated from mouse embryos were cultured on the substrate of recombinant mouse TLCN protein. Hippocampal neurons extended multiple neurites on TLCN. The neurite outgrowth on TLCN was suppressed by an anti-TLCN antibody. Non-telencephalic neurons also extended neurites on TLCN. These results demonstrate a neurite outgrowth-promoting activity of TLCN and suggest that both telencephalic and non-telencephalic neurons express TLCN counter-receptor(s) which is coupled to the neurite outgrowth.

Animals↗
PubMed1998

Heterogeneity of ictal SPECT findings in nine cases of West syndrome.

We evaluated the ictal and interictal single photon emission computed tomography (SPECT) of 9 patients with West syndrome (WS). In this group, we noted two clear patterns of cortical hyperperfusion and subcortical hyperperfusion in the ictal SPECT. Both patterns were different from the previously documented ictal patterns for complex partial seizures (CPS) or secondarily generalized seizures. Our results suggest that the tonic spasms of WS do not always have a single neurophysiological basis; e.g., patients with hemihypsarrhythmia and focal hypsarrhythmia did not show ictal hyperperfusion of the lesion with hypsarrhythmia. These findings indicate that the origin of hypsarrhythmia as an EEG feature and the origin of tonic spasms may be different in such patients. In particular, hypsarrhythmia appears to originate from cortical lesions, whereas the subcortical structures may be primarily responsible for the tonic spasms. Our report is the first published study of ictal SPECT in patients with WS.

Adolescent↗
PubMed1998

Chondrocalcin as a marker of articular cartilage degeneration in anterior cruciate ligament-deficient knees.

This study assessed articular cartilage deterioration and the effect of meniscal tears to evaluate the usefulness of chondrocalcin as a joint fluid marker in 43 patients with anterior cruciate ligament (ACL) deficiency. A significant correlation was found between the cartilage damage and time after injury. The high incidence of long longitudinal tears of the medial meniscus with increased cartilage damage, especially in chronic cases, suggests that this type of meniscal tear contributed to the deterioration of ACL-deficient knees. Chondrocalcin concentrations were found to have a significant correlation with cartilage damage.

Adolescent↗
PubMed1997

OCAM: A new member of the neural cell adhesion molecule family related to zone-to-zone projection of olfactory and vomeronasal axons.

Zone-to-zone projection of olfactory and vomeronasal sensory axons underlies the topographic and functional mapping of chemoreceptor expression zones of the sensory epithelia onto zonally arranged glomeruli in the main and accessory olfactory bulbs. Here we identified OCAM (R4B12 antigen), an axonal surface glycoprotein expressed by subsets of both olfactory and vomeronasal axons in a zone-specific manner. OCAM is a novel homophilic adhesion molecule belonging to the immunoglobulin superfamily with striking structural homology to neural cell adhesion molecule. In both the main and accessory olfactory systems, OCAM mRNA is expressed by sensory neurons in restricted chemoreceptor expression zones, and OCAM protein-expressing axons project to the glomeruli in the corresponding zones of the main and accessory bulbs. OCAM protein is expressed on subsets of growing sensory axons in explant cultures even in the absence of the target bulb. These results demonstrate a precisely coordinated zonal expression of chemoreceptors and OCAM and suggest that OCAM may play important roles in selective fasciculation and zone-to-zone projection of the primary olfactory axons.

Amino Acid Sequence↗
PubMed1997

OCAM reveals segregated mitral/tufted cell pathways in developing accessory olfactory bulb.

Two functional subsets of vomeronasal sensory neurons project their axons to two segregated zones in the accessory olfactory bulb (AOB). Using immunohistochemical methods with antibodies against the novel cell adhesion molecule OCAM, we provide evidence that the segregation of functional pathways is maintained at the level of mitral/tufted (M/T) cells of the mouse AOB and that this pattern emerges early in ontogeny. During embryonic and postnatal development OCAM was strongly expressed by M/T cells in the caudal zone of the AOB where OCAM-negative vomeronasal axons terminated. In contrast, rostral zone M/T cells innervated by OCAM-positive vomeronasal axons displayed no or faint OCAM immunoreactivity. Differential expression of OCAM in segregated M/T cell pathways suggests that OCAM may be involved in defining compartments of connectivity and setting up functional subdivisions in the developing AOB.

Aging↗
PubMed1997

Genomic organization and chromosomal localization of the mouse telencephalin gene, a neuronal member of the ICAM family.

Telencephalin is a cell adhesion molecule belonging to the immunoglobulin (Ig) superfamily, whose expression is restricted to subsets of neurons in the telencephalon, the most rostral segment of brain. Of all the Ig superfamily molecules so far identified, the structure of telencephalin is most closely related to those of intercellular adhesion molecules (ICAMs)-1 and -3. Here we report the cloning, characterization, and chromosomal localization of the mouse telencephalin gene (Tlcn). The Tlcn gene spanned about 6.3 kb and consisted of 11 exons. A signal peptide and individual nine Ig-like domains of telencephalin were encoded by a single exon, while the transmembrane and cytoplasmic regions were fused in a same exon. The primer extension technique was used to establish that the transcription initiation sites were located 92-95 bp upstream from the ATG start codon. DNA sequencing of the 5'-flanking region revealed the presence of a strong initiator element for TATA-less genes, two CAAT boxes, and numerous potential transcription factor binding sites including four E-box and two N-box sequences. Interspecific backcross analysis demonstrated that the Tlcn gene was mapped in the proximal region of mouse chromosome 9 in close vicinity to the Icam-1 gene, suggesting that Tlcn and Icam-1 are derived from a common ancestral gene by gene duplication.

Animals↗
PubMed1997

Reduction of telencephalin immunoreactivity in the brain of patients with Alzheimer's disease.

Telencephalin (TLN) is a cell adhesion molecule expressed in the telencephalon of the mammalian central nervous system. We have investigated immunohistochemically the expression of TLN in human brain tissue from control subjects and patients with Alzheimer's disease (AD). In control brain, neuropil of the gray matter was stained diffusely with the anti-TLN antibody. TLN immunoreactivity was markedly decreased in the brain of AD patients, particularly in the hippocampal formation.

Aged↗
PubMed1997

The neuronal glycoprotein telencephalin is a cellular ligand for the CD11a/CD18 leukocyte integrin.

Many leukocyte functions depend on interactions between the leukocyte-specific beta2 integrins CD11/CD18 and their ligands, the intercellular adhesion molecules (ICAMs). Telencephalin (TLN) is a novel member of the Ig superfamily expressed in the central nervous system. The NH2-terminal five Ig-like domains of TLN show the highest homology with the Ig domains of ICAM-1, ICAM-2, ICAM-3, and LW (ICAM-4), the known cellular ligands for CD11a/CD18. Here, we demonstrate that TLN interacts with CD11a/CD18. Peripheral blood T cells, Jurkat T cells, and B lymphoblastoid cells bound to immunopurified recombinant human TLN proteins. This adhesion was through CD11a/CD18 and was significantly inhibited by an Ab to CD11a/CD18. Reciprocally, TLN-transfected L cells also bound to purified CD11a/CD18. Recombinant TLN proteins comprising either the first five Ig domains (TLN(1-5)) or the entire extracellular portion (TLN(1-9)) showed binding to CD11a/CD18. We conclude that TLN is a novel neuronal cell adhesion molecule that may be important in integrin-mediated cell-cell interactions in the central nervous system, and that the CD11a/CD18-dependent recognition site of human TLN is located within the NH2-terminal five domains of this molecule.

Amino Acid Sequence↗
PubMed1997

cDNA cloning and chromosomal localization of the human telencephalin and its distinctive interaction with lymphocyte function-associated antigen-1.

We have isolated cDNA encoding human telencephalin (TLN), a brain segment-specific neuronal adhesion molecule. Human TLN comprises an NH2-terminal signal peptide, an extracellular region with nine Ig-like domains, a single transmembrane region, and a COOH-terminal cytoplasmic tail. The NH2-terminal five Ig-like domains of TLN were closely related to those of intercellular adhesion molecules (ICAMs)-1 and -3. The TLN gene was mapped to the human chromosome 19p13.2, where the ICAM-1, -3, and -4 (LW) genes are located. Furthermore, we observed lymphocyte function-associated antigen-1 (LFA-1)-mediated adhesion of HL-60 cells on recombinant TLN protein, as well as on ICAM-1. However, the interaction of TLN with LFA-1 on HL-60 cells was divalent cation-independent and phorbol 12-myristate 13-acetate stimulation-independent. We conclude that TLN is a unique neuronal member of ICAM subgroup of the Ig superfamily and propose a novel type of interaction between the Ig superfamily molecule and integrin, which does not require the activation of integrin. TLN on the surface of telencephalic neurons may be a target molecule in the brain for LFA-1-expressing microglia and leukocytes in physiological or pathological conditions.

Amino Acid Sequence↗
PubMed1997

Basic principles and molecular mechanisms of olfactory axon pathfinding.

The present review describes several lines of recent evidence providing new insights into the basic principles and mechanisms of axon projection from the olfactory epithelium to the olfactory bulb. Olfactory sensory neurons are classified into approximately 1000 subtypes according to the expression of specific odorant receptors. Olfactory sensory neurons expressing a given odorant receptor are distributed within one zone out of the four circumscribed zones of the olfactory epithelium and send their axons to the corresponding zone of the olfactory bulb: the principle of zone-to-zone projection. We discuss possible functions of a novel cell adhesion molecule, viz., OCAM, in the formation and maintenance of zone-to-zone projection of both olfactory and vomeronasal axons. Furthermore, olfactory sensory neurons expressing a given odorant receptor converge their axons onto only two topographically fixed glomeruli among the 1500-3000 glomeruli in the olfactory bulb: the principle of glomerular convergence. These axonal connection patterns give rise to the response specificity of the second-order neurons, viz., the mitral/tufted cells, to a particular range of odor molecules. In the process of glomerular convergence, combinatorial functions of axon-associated cell adhesion molecules and odorant receptor proteins may be required for the establishment of the precise targeting of olfactory axons to the appropriate glomeruli.

Animals↗
PubMed1997

Mice lacking the vitamin D receptor exhibit impaired bone formation, uterine hypoplasia and growth retardation after weaning.

1 alpha,25-Dihydroxyvitamin D3[1 alpha,25(OH)2D3], an active form of vitamin D, has roles in many biological phenomena such as calcium homeostasis and bone formation, which are thought to be mediated by the 1 alpha,25(OH)2D3 receptor (VDR), a member of the nuclear hormone receptor superfamily. However, the molecular basis for the actions of 1 alpha,25(OH)2D3 in bone formation, its role during development and VDR genetic polymorphisms for predicting bone mineral density are uncertain. To investigate the functional role of VDR, we generated mice deficient in VDR by gene targeting. We report here that in VDR null mutant mice, no defects in development and growth were observed before weaning, irrespective of reduced expression of vitamin D target genes. After weaning, however, mutants failed to thrive, with appearance of alopoecia, hypocalcaemia and infertility, and bone formation was severely impaired as a typical feature of vitamin D-dependent rickets type II (refs 8, 9). Unlike humans with this disease, most of the null mutant mice died within 15 weeks after birth, and uterine hypoplasia with impaired folliculogenesis was found in female reproductive organs. These defects, such as alopoecia and uterine hypoplasia, were not observed in vitamin D-deficient animals. The findings establish a critical role for VDR in growth, bone formation and female reproduction in the post-weaning stage.

Alopecia↗
PubMed1997

Synovial fluid concentrations of the C-propeptide of type II collagen correlate with body mass index in primary knee osteoarthritis.

OBJECTIVE: To explore in a cross sectional study in patients with primary knee osteoarthritis (OA) the relations between body mass index (BMI), disease stage, and the concentrations of a putative joint fluid marker of type II collagen synthesis, procollagen II C-propeptide. PATIENTS AND METHODS: The study included 142 patients with knee OA (median age 68, median BMI 24.1). OA was staged radiologically. The concentrations in synovial fluid of procollagen II C-propeptide were measured by a sandwich enzyme immunoassay. RESULTS: Joint fluid concentrations of procollagen II C-propeptide were increased in knees with OA (median 3.7 ng/ml), compared with published reference values for knees in healthy adult volunteers (median 1.3 ng/ml). The concentrations of procollagen II C-propeptide were independently related to both OA stage and BMI (r = 0.343, p < 0.0001 and r, = 0.253, p = 0.002, respectively). CONCLUSIONS: Joint fluid concentrations of this putative marker of collagen II synthesis are high in early and mid-stage OA, but decrease in end stage disease. In addition and for the first time it was shown that the concentrations in synovial fluid of procollagen II C-propeptide increase with increasing BMI in primary knee OA. The increased joint fluid values of this marker in patients with primary knee OA and a high BMI, may reflect increased rates of collagen synthesis in their joint cartilage and could relate to the previously shown increased risk for disease progression in such patients.

Adult↗