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Biomedical subjects

H Ichijo

Publications and source records attributed to H Ichijo.

At least 73 records · Page 4Linked to original sources
PubMed1996

[Follow-up study of vestibular neuronitis].

A follow-up study of 26 patients with vestibular neuronitis is reported. The disease is characterized by an acute attack of severe vertigo with complete loss of unilateral caloric response. The following results were obtained: 1) The average period of spontaneous nystagmus was 136 days and the standard error was 39 days. 2) No correlation could be found between age and the period of spontaneous nystagmus. 3) Six patients showed direction reversal in their spontaneous nystagmus (recovery nystagmus), and their outcome was good. 4) On the most recent caloric test, 42% of the patients had bilateral normal responses, 27% displayed partial improvement on the affected side, and no reaction was observed in 31% of patients. We suggest that three types of clinical courses may occur in vestibular neuronitis: i) complete recovery of the function of the affected vestibular nerve, ii) partial recovery of vestibular function, and iii) no recovery of the affected vestibular nerve, but central nervous system compensates for the vestibular imbalance.

Adolescent↗
PubMed1995

Efficient association of an amino-terminally extended form of human latent transforming growth factor-beta binding protein with the extracellular matrix.

Latent transforming growth factor-beta (TGF-beta) binding protein-1 (LTBP-1) is a component of the high molecular weight latent TGF-beta complex found in various cells, including human platelets. LTBP-1 is observed as different molecular sizes in different cell types, probably due to proteolytic processing and alternative splicing. We here report a novel form of human LTBP-1, which is longer in its NH2-terminal part (LTBP-1L). Northern hybridization analysis revealed that the LTBP-1L is derived from a 7.0-kilobase mRNA, whereas the originally reported shorter form (LTBP-1S) is derived from a 5.2-kilobase mRNA. Transfection of cDNA for LTBP-1L and -1S in COS cells revealed that LTBP-1L bound more efficiently to the extracellular matrix than did LTBP-1S. These results suggest that the different splice forms of LTBP-1 mediate different localization patterns of the latent TGF-beta complexes in vivo.

Amino Acid Sequence↗
PubMed1995

Localization of transforming growth factor-beta type I and type II receptors in mouse development.

We have investigated the localization pattern of the transforming growth factor-beta (TGF-beta) receptors type I (T beta R-I) and type II (T beta R-II) during mouse organogenesis by immunohistochemical analysis. Staining of both receptors was found in many developing organs, e.g., bone, teeth, Meckel's cartilage, and neural tissues, where the expression of their ligands has been previously reported. During the investigated stages, expression of T beta R-I was more ubiquitous than that of T beta R-II. T beta R-II preferentially localized in the undifferentiated mesenchymal cells which subsequently differentiated into bone. There was no staining of T beta R-II in the central nervous system, while intense T beta R-I staining was found specifically in nervous tissues. Expression of T beta R-I and T beta R-II was mostly coincident with that of their ligands, suggesting that TGF-beta s act as multiple mediators during organogenesis. In addition, colocalization of both receptors in the epithelia of the tooth bud and submandibular gland, which were actively invaginating into the mesenchyme, leads us to speculate that both receptors may be necessary for dynamic epithelial morphogenesis.

Activin Receptors, Type I↗
PubMed1995

Vestibular function in bilateral progressive sensorineural hearing loss.

To investigate the vestibular function in patients with bilateral progressive sensorineural hearing loss, we examined 5 cases using electronystagmography. Cases 1, 2 and 3 were adult type, and Cases 4 and 5 juvenile type. All patients had dizzy spells in the early stage of the disease, and showed spontaneous nystagmus. Bilateral reduction of caloric response and very low vestibulo-ocular reflex (VOR) gain on rotation testing were observed in Cases 1, 2 and 3. Case 4 showed right canal paresis upon the caloric test and left directional preponderance upon the rotation test. Case 5 showed good responses to both tests. Optokinetic afternystagmus (OKAN) in Cases 2, 3 and 5 was not brisk, and Cases 1 and 2 showed directional preponderance of OKAN. OKAN was useful for detecting directional preponderance. We believe there are two types of this disease which correlate with vestibular function. One type is associated with high grade vestibular dysfunction while, in the other, vestibular function is reasonably good.

Adult↗
PubMed1995

Observation of positional nystagmus with infrared CCD camera.

Using infrared CCD camera and electronystagmography we analyzed positional nystagmus in 33 patients with peripheral positional vertigo. Patients were classified into three types; (a) lateral type: nystagmus occurs in lateral position, (b) sagittal type: nystagmus occurs in head-hanging position (so-called benign paroxysmal positional vertigo, BPPV), and (c) mixed type. Nystagmus in the lateral type was horizontal and that in the sagittal type was rotatory. In all types, the vertigo and nystagmus began with a few seconds' latency after head tilt and briefly increased to a maximum, and then gradually decreased. The duration of horizontal nystagmus in the lateral and mixed type was significantly longer than that of rotatory nystagmus in the sagittal type mixed type. The mean value of the former was 90.6 s and that of the latter 18.1 s. We suggest that the velocity storage mechanism of the horizontal vestibulo-ocular reflex (VOR) is considerably different from that in the vertical VOR.

Adolescent↗
PubMed1994

Identification and characterization of autocrine-motility-factor-like activity in oral squamous-cell-carcinoma cells.

A human oral squamous-cell-carcinoma cell line, HOC313, was found to produce a factor which stimulates cell motility in an autocrine manner. The motility factor of HOC313 cells also promoted the locomotory activity of B16 murine melanoma cells reported to be sensitive to autocrine motility factor (AMF). HOC313 cells were found to express a large amount of AMF-receptor mRNA. In addition, the cell motility activity of HOC313 cells was completely blocked by pertussis toxin, a known inhibitor of AMF activity, suggesting that the motility factor of HOC313 cells may be AMF or a closely related factor. Immunocytochemical analysis has revealed that the AMF-like factor of HOC313 cells diminishes the cell-surface expression of adhesive molecule E-cadherin. These results suggest that down-regulation of E-cadherin may be involved in the cell-motility activity induced by the AMF-like factor of HOC313 cells.

Animals↗
PubMed1994

Modulation of responses to TGF-beta by 1, 25 dihydroxyvitamin D3 in MG-63 osteoblastic cells: possible involvement of regulation of TGF-beta type II receptor.

The effect of TGF-beta 1 on the expression of alkaline phosphatase (ALPase) activity was examined during osteoblastic cell line (MG-63) differentiation induced by 1,25-dihydroxyvitamin D3 (1,25D3). TGF-beta 1 and 1,25D3 were found to enhance ALPase activity. However, preincubation of the cells with 1,25D3 transiently abolished the effects of TGF- beta 1. Kinetics of the complex responses to TGF- beta 1 and 1,25D3 were found to correlate well with that of the expression level of type II receptor for TGF- beta. These results suggest that 1,25D3 may regulate the cellular responses to TGF- beta 1 in part via regulation of functional receptor for TGF- beta.

Alkaline Phosphatase↗
PubMed1994

Molecular cloning of rat bone morphogenetic protein (BMP) type IA receptor and its expression during ectopic bone formation induced by BMP.

A cDNA for the rat bone morphogenetic protein (BMP) type IA receptor (BMPR-IA) was isolated from a dental pulp cell cDNA library. The rat BMPR-IA cDNA encodes a protein of 532 amino acids with a single transmembrane domain and a putative serine/threonine kinase domain. The overall amino acid sequence identity between the rat and human BMPR-IA was 97%. Reverse transcriptase-polymerase chain reaction analysis revealed that BMPR-IA mRNA was highly expressed in the BMP-induced bone forming tissues throughout the stages tested.

Amino Acid Sequence↗
PubMed1994

Identification of type I receptors for osteogenic protein-1 and bone morphogenetic protein-4.

Bone morphogenetic proteins (BMPs) are multifunctional proteins, structurally related to transforming growth factor-beta (TGF-beta) and activin. TGF-beta and activin exert their effects by forming heteromeric complexes of type I and type II serine/threonine kinase receptors. We have previously identified a series of type I serine/threonine kinase receptors, termed activin receptor-like kinase (ALK)-1 to -6. ALK-5 is a TGF-beta type I receptor, whereas ALK-2 and ALK-4 are activin type I receptors. Here we investigated the binding of proteins in the BMP family to ALKs. In transfected COS cells, the binding of osteogenic protein (OP)-1 and BMP-4 to certain ALKs was observed in the absence of type II receptors, and their binding was increased after co-transfection of a BMP type II receptor from Caenorhabditis elegans, DAF-4. OP-1 bound to ALK-2 and ALK-6 efficiently, and to ALK-3 less efficiently, whereas BMP-4 bound to ALK-3 and ALK-6 efficiently. Similarly, OP-1 bound to ALK-2, ALK-3, and/or ALK-6 in various nontransfected cell lines, although the binding profiles were different between different cell types. BMP-4 bound to ALK-3 in MC3T3-E1 osteoblasts and human foreskin fibroblasts. These results suggest that ALK-3 and ALK-6 are type I receptors for OP-1 and BMP-4; in addition, ALK-2 is a type I receptor shared by activin and OP-1, but not by BMP-4.

Activin Receptors↗
PubMed1994

Characterization of type I receptors for transforming growth factor-beta and activin.

Transforming growth factor-beta (TGF-beta) and activin exert their effects by binding to heteromeric complexes of type I and type II receptors. The type II receptors for TGF-beta and activin are transmembrane serine-threonine kinases; a series of related receptors, denoted activin receptor-like kinase (ALK) 1 to 5, have recently been identified, and ALK-6 is described here. ALK-5 has been shown to be a functional TGF-beta type I receptor. A systematic analysis revealed that most ALKs formed heteromeric complexes with the type II receptors for TGF-beta and activin after overexpression in COS cells; however, among the six ALKs, only ALK-5 was a functional TGF-beta type I receptor for activation of plasminogen activator inhibitor-1, and only ALK-2 and ALK-4 bound activin with high affinity.

Activin Receptors↗
PubMed1994

Endoglin forms a heteromeric complex with the signaling receptors for transforming growth factor-beta.

Human endoglin is a dimeric protein that binds transforming growth factor-beta (TGF-beta). A porcine cDNA clone for endoglin was obtained from a porcine uterus cDNA library. The deduced sequence of the primary translated product of endoglin consists of 643 amino acids with a high sequence identity (96%) to human endoglin in the transmembrane and intracellular domains, but with a lower sequence similarity (66%) in the extracellular domain. In contrast to human endoglin, porcine endoglin has no Arg-Gly-Asp tripeptide in its sequence. Antibodies, raised against a peptide corresponding to the intracellular domain of porcine endoglin, immunoprecipitated an 84-kDa protein under reducing condition and a 130-kDa protein under nonreducing condition in porcine aortic endothelial cells. Porcine endoglin bound TGF-beta 1 and -beta 3 efficiently, but TGF-beta 2 less efficiently. Endoglin was found to be coimmunoprecipitated with TGF-beta receptors type I and/or II by the endoglin antibodies or by TGF-beta receptor II antibodies in the presence of ligand. Thus, endoglin and TGF-beta receptors I and/or II most likely formed a heteromeric receptor complex. Endoglin was phosphorylated on serine residue(s), which did not change after stimulation by TGF-beta 1. These results revealed that endoglin is a phosphorylated protein which forms a heteromeric complex with signaling receptors for TGF-beta.

Amino Acid Sequence↗
PubMed1994

Serine/threonine kinase receptors.

A new family of transmembrane receptors that contain intracellular serine/threonine kinase domains is emerging. Ligands for this class of receptors include members of the transforming growth factor-beta (TGF-beta) superfamily, e.g. TGF-beta s and activins. TGF-beta s exert their effects on target cells via formation of heteromeric serine/threonine kinase complexes (TGF-beta type I and type II receptors). Other components, i.e. TGF-beta type III receptor and endoglin, appear to have more indirect roles, e.g. to present ligands to the signalling receptors. Given the structural similarity between members of the TGF-beta superfamily, other ligands in this family may act through structurally and functionally similar serine/threonine kinase receptors.

Amino Acid Sequence↗
PubMed1994

[Vestibular function in bilateral idiopathic progressive sensorineural hearing loss].

To investigate vestibular function in patients with bilateral progressive sensorineural hearing loss (BPSHL), we examined 5 cases using electronystagmography. Cases 1, 2 and 3 were adult type, cases 4 and 5 were juvenile type. All patients had dizzy spells in the early stage of the disease, and showed spontaneous nystagmus. Bilateral reduction of caloric response and very low VOR (vestibulo-ocular reflex) gain on rotation testing were observed in cases 1, 2 and 3. Case 4 showed right canal paresis on the caloric test and left directional preponderance on the rotation test. Case 5 showed good responses to both tests. Optokinetic afternystagmus (OKAN) in cases 2, 3 and 5 was not brisk, and cases 1 and 4 showed directional preponderance of OKAN. Although OKAN is useful for detecting directional preponderance, it does not always reflect peripheral vestibular function. We suggest the existence of two types of BPSHL which correlate with vestibular function. One type is associated with high grade vestibular dysfunction while, in the other, vestibular function is fair.

Adolescent↗
PubMed1994

Enhanced expression of transforming growth factor-beta s and transforming growth factor-beta type II receptor in the synovial tissues of patients with rheumatoid arthritis.

BACKGROUND: A growing body of evidences suggests that transforming growth factor-beta (TGF-beta) is produced in the synovial fluid of patients with rheumatoid arthritis (RA), and that TGF-beta is an important regulator in the course of the disease. Careful studies on the endogenous synthesis of TGF-beta as well as its receptors are therefore necessary to clarify the possible role of TGF-beta in RA. EXPERIMENTAL DESIGN: We examined the expressions of latent TGF-beta 1, -beta 2, and -beta 3, the latent TGF-beta 1-binding protein (LTBP) as well as TGF-beta type II receptor (TGF-beta RII) in the synovial biopsy tissues of 21 patients with RA by immunohistochemistry. Five specimens from these cases representing both active and chronic inactive stages were also examined for the corresponding mRNA by in situ hybridization. Northern blot analysis was performed on 3 synovial membranes taken from the RA patients together with a control synovium. RESULTS: Abundant LTBP, TGF-beta 1, and TGF-beta RII-positive cells as well as less intensively stained TGF-beta 2 and TGF-beta 3-positive cells were found in the synovial layer. These cells were positive for the histocompatibility antigen, HLA-DR. In lymphocyte aggregates, scattered cells positively labeled for LTBP and TGF-beta 1 were found. They stained in a reticular pattern that was similar to that demonstrated by an antibody against human dendritic cells, and also expressed HLA-DR. In situ hybridization revealed markedly increased signals for LTBP and TGF-beta RII mRNA in tissues with an active inflammatory process, when compared with tissues with less active inflammation. However, no clear differences in the levels of expression for any of the TGF-beta isoforms were found. Specimens with pronounced fibrosis, fibroblasts, and surrounding collagen fibers expressed positive immunoreactivities for all TGF-beta isoforms and LTBP. Northern blot analysis on 4 synovial tissues demonstrated positive signals for LTBP and TGF-beta 1 mRNA in all three RA patients in contrast to a normal control, which did not show any signals. An increased expression of TGF-beta RII mRNA was detected in the tissue from one of the patients. CONCLUSIONS: An abundant expression of TGF-beta 1 and LTBP, as well as TGF-beta RII was seen in most actively proliferating synovial intimal cells, and the level of the expression varied during the course of the disease. We conclude that TGF-beta is involved tightly in the regulation of the inflammatory process, and it is thus possible that the endogenous TGF-beta functions as a self-regulator that induces the remission periods.

Amino Acid Sequence↗
PubMed1993

Cloning of a TGF beta type I receptor that forms a heteromeric complex with the TGF beta type II receptor.

A cDNA clone encoding a 53 kd serine/threonine kinase receptor with an overall structure similar to that of the type II receptor for transforming growth factor beta (TGF beta) was obtained. 125I-TGF beta 1 bound to porcine endothelial cells transfected with the cDNA and formed a cross-linked complex of 70 kd, characteristic of a TGF beta type I receptor. Immunoprecipitation of the cross-linked complexes by antibodies against the cloned receptor revealed the 70 kd complex as well as a 94 kd TGF beta type II receptor complex. The immunoprecipitated novel serine/threonine kinase receptor had biochemical properties of the TGF beta type I receptor and was observed in different cell types. Transfection of the cloned cDNA into TGF beta type I receptor-deficient cells restored TGF beta-induced plasminogen activator inhibitor 1 production. These results suggest that signal transduction by TGF beta involves the formation of a heteromeric complex of two different serine/threonine kinase receptors.

Amino Acid Sequence↗
PubMed1993

Characterization of in vivo phosphorylation of activin type II receptor.

An antiserum was generated against a C-terminal peptide of the mouse activin type II receptor (ActR-II), which specifically immunoprecipitates ActR-II protein transiently expressed in COS-1 cells. Autophosphorylation activity of the ActR-II was examined in [32P]orthophosphate labeled COS-1 cells. The immunoprecipitated ActR-II protein was found to be phosphorylated on serine residues in the absence of ligand stimulation, and the phosphorylation was slightly increased after stimulation with activin A.

Activin Receptors↗
PubMed1993

Molecular cloning and characterization of ficolin, a multimeric protein with fibrinogen- and collagen-like domains.

We have previously identified and purified transforming growth factor-beta 1 (TGF-beta 1)-binding proteins from porcine uterus membranes (Ichijo, H., Rönnstrand, L., Miyagawa, K., Ohashi, H., Heldin, C.-H., and Miyazono, K. (1991) J. Biol. Chem. 266, 22459-22464). One of these TGF-beta 1-binding proteins, with a molecular weight of 40,000, was purified to homogeneity and subjected to amino acid sequence analysis. The amino acid sequences obtained were used to isolate two closely related cDNA clones from a porcine uterus cDNA library. The deduced amino acid sequences revealed that both cDNAs encoded proteins that were mainly composed of fibrinogen-like and collagen-like domains. Therefore, they were denoted ficolin-alpha and ficolin-beta. Expression of ficolin-alpha and -beta cDNA in mammalian cells revealed that ficolin forms dimers, trimers, and several higher order of oligomers, whose molecular weights fit well with those of the purified TGF-beta 1-binding proteins from porcine uterus. Moreover, immunoblotting analysis using a peptide anti-serum against ficolin indicated that the TGF-beta 1-binding proteins identified in porcine uterus are ficolin-alpha, -beta, and their oligomers or closely related molecules. However, recombinant ficolin-alpha and -beta did not bind TGF-beta 1, despite the similarities in molecular weights and immunoreactivity with the material from the natural source. It is possible that a specific posttranslational modification of ficolin or interaction with another component is needed for TGF-beta 1 binding. Analysis by Northern blotting revealed that the expression of ficolin-alpha mRNA is relatively restricted and most abundant in placenta and lung. On the other hand, ficolin-beta was mainly expressed in skeletal muscle. The in vivo functions of ficolin will be discussed.

Amino Acid Sequence↗