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Biomedical subjects

T Tsuru

Publications and source records attributed to T Tsuru.

At least 37 records · Page 2Linked to original sources

Prenatal diagnosis of Lowe syndrome by OCRL1 messenger RNA analysis.

Prenatal screening of oculo-cerebro-renal syndrome of Lowe (OCRL; McKusick 309000) was performed using cultured amniocytes. Following identification of defective mRNA expression in the OCRL; gene of the proband's fibroblasts, the mRNA size and quantity of the cultured amniocytes were compared. Based on this analysis, the fetus was diagnosed as being normal and was subsequently delivered as a healthy boy. This is the first reported successful prenatal screening of OCRL using a comparison with defective mRNA of OCRL1 from affected subjects.

Adolescent↗

Expression of transforming growth factor-beta superfamily receptors in rat eyes.

PURPOSE: Transforming growth factor-beta (TGF-beta) superfamily consists of many multifunctional cytokines including TGF-beta, activins, and bone morphogenetic proteins (BMPs). Previous reports show that these factors are expressed in ocular tissue, and exert their effects through type I and type II serine/threonine type receptors. The purpose of this study is to observe the expression of these receptor families in normal rat eyes as the first step in investigating the functions of TGF-beta superfamily members in ocular tissue. METHODS: The expression of receptors was examined immunohistochemically in one eye each of 6 Lewis rats. The type I receptors examined were the TGF-beta type I receptor (TbetaR-I), activin type I receptor (ActR-I), activin type IB receptor (ActR-IB), bone BMP type IA receptor (BMPR-IA), BMP type IB receptor (BMPR-IB), and activin receptor-like kinase-1 (ALK-1). The type II receptors examined were TGF-beta type II receptor (TbetaR-II), activin type II receptor (ActR-II), and BMP type II receptor (BMPR-II). RESULTS: All 6 type I receptors, ActR-II and the alternative spliced long version of BMPR-II were expressed in the following cells: corneal and conjunctival epithelium, corneal keratocytes, corneal endothelium, epithelium of iris and ciliary body, epithelium of lens, sensory retina excluding the outer segments of photoreceptors, retinal pigment epithelium (RPE), and vascular cells. TbetaR-II and the short version of BMPR-II (truncated form) were expressed in the outer segments of the photoreceptors in addition to the above. The results of staining were similar in all the sections examined. CONCLUSIONS: The cornea, ciliary body, iris, lens, retinal cells, RPE and vascular cells expressed the receptors for TGF-beta superfamily at protein level.

Activin Receptors, Type I↗

ABO antigen blood-group compatibility and allograft rejection in corneal transplantation.

PURPOSE: To evaluate effects of ABO antigen blood-group matching on the rates of corneal allograft rejection after penetrating keratoplasty. METHODS: We retrospectively studied clinical results of penetrating keratoplasties in terms of graft survival rates and rejection-free graft survival rates. Penetrating keratoplasties were done on 95 eyes between 1993 and 1997. Clinical results were analyzed using the Kaplan-Meier life table method and log-rank test. The corneal transplantations were classified into 2 groups, high-risk (35 eyes) and low-risk (60 eyes) transplantations. High-risk transplantation was defined as significant vascularization in the recipient corneas or a history of graft failure. The remaining transplantations were defined as low-risk. RESULTS: The respective graft survival (p = 0.031) and rejection-free graft survival (p = 0.0097) rates were higher in the low-risk than in the high-risk group. In the high-risk group, the rejection-free graft survival was 68.9% for the ABO-compatible subgroup and 36.4% for the ABO-incompatible subgroup (p = 0.007). CONCLUSION: ABO matching is effective in reducing the risk of allograft rejection in high-risk corneal transplantations.

ABO Blood-Group System↗

Carpal tunnel syndrome involving unaffected limbs of stroke patients.

BACKGROUND AND PURPOSE: Stroke-induced hemiparesis involving the arm and hand results in regular, repeated overuse of the opposite hand and wrist. Because repetitive hand and wrist movement is a common cause of carpal tunnel syndrome (CTS), we examined the nonparetic upper limb in stroke patients for evidence of CTS. METHODS: We measured bilaterally sensory nerve conduction velocity (SNCV), motor nerve conduction velocity (MNCV), sensory nerve action potentials (SNAP) at the wrist, palm-to-wrist distal sensory latency (DSL), palm-to-wrist SNAP, compound motor action potentials (CMAP), and distal motor latency (DML) in stroke patients and control subjects. Controls were right-handed, >/=65 years old, lucid, independent in their activities of daily living, and had no disease known to cause CTS. Stroke patients were divided into a functioning hand group (n=61) and a disused hand group (n=71). All patients had hemiplegia. RESULTS: Tinel's sign was observed on the nonparetic side in 57.7% of patients with a disused hand and in 31.1% of those with a functioning hand. All electrophysiological indices were significantly more abnormal on the nonparetic side than on the hemiparetic side or in controls. Patients with a disused hand showed greater abnormality on the nonparetic side in SNCV, SNAP, palm-to-wrist DSL, DML, and CMAP than patients with a functioning hand. CONCLUSIONS: Overuse of the nonparetic hand and wrist of the nonparetic side may result in CTS in stroke patients, especially when the paretic hand is not functional. Wrist splinting or other prophylactic treatments beginning soon after stroke might help to prevent CTS.

Aged↗

Dermatomyositis associated with invasive thymoma.

We report a case of dermatomyositis (DM) associated with invasive thymoma in a 22-year-old woman who was admitted to our hospital complaining of dyspnea which required ventilation support. The reddened elevated scaly eruptions were prominent over the extensor surfaces. Chest X-ray and computed tomography showed mediastinal masses, which were diagnosed as mixed type thymoma. Muscle and skin biopsy specimens were compatible with DM. She was treated with methylprednisolone pulse therapy followed by extended removal of the anterior mediastinal tumor and subsequent radiotherapy. She has had a good clinical course without recurrence of thymoma or DM for more than 3 years. The role of thymoma in the development of DM is discussed.

Adult↗

[A case of ophthalmoplegic migraine: swelling and Gd-DTPA enhancement of the oculomotor nerve on MRI].

We report here a 9-year-old girl with ophthalmoplegic migraine. At the age of 2 years and 6 months she first developed left ptosis and ophthalmoparesis that resolved gradually within 2 weeks. She experienced similar episodes repeatedly. After 5 years of age, left periorbital pulsatile pain preceded ptosis and ophthalmoparesis, and after 7 years, she showed permanent left third nerve paresis even between the attacks. On cranial MRI the left oculomotor nerve showed swelling and contrast enhancement, the latter being more prominent in the ictal than interictal images. Ophthalmoplegic migraine should be considered in the differential diagnosis of opthalmoplegia in children even in the absence of headache. The diagnosis is strongly suspected when MRI demonstrates swelling and enhancement of the oculomotor nerve.

Child↗

[Long-term outcome of topical cyclosporine treatment following penetrating keratoplasty].

PURPOSE: To evaluate the long-term outcome of 2% topical cyclosporine A (CsA) treatment as an adjunct to topical corticosteroid in 86 eyes after penetrating keratoplasty (PK). MATERIAL AND METHODS: The subjects were 86 eyes of 83 patients who had undergone PK and received topical CsA treatments. Ninety-seven eyes of 95 patients who had undergone PK and received similar postoperative treatments except for topical CsA treatments served as control: The clinical outcome of PK was evaluated by rates of graft survival and rejection-free graft survival using Kaplan-Meier's method and compared with the log-rank test. The patients were subdivided into high-risk and low-risk groups. The high-risk patients were those who had corneal vascularization in 2 or more quadrants of the cornea preoperatively or who received regrafting. All other patients were assigned to the low-risk group. Thirty-six eyes of the CsA group and 50 eyes of the control group were high-risk cases. RESULTS: In the high-risk patients, the rejection-free graft survival rate was 69.7% in the CsA group and 45.4% in the control group (p = 0.030). However, there was no significant difference in the graft survival rate between the two groups. In the low-risk patients, there was no significant difference in the rates of rejection-free graft survival and graft survival between the CsA and the control group. CONCLUSION: 2% topical cyclosporine is effective in reducing the risk of allograft rejection in high-risk recipients.

Administration, Topical↗

Increase in orthotopic murine corneal transplantation rejection rate with anterior synechiae.

PURPOSE: To evaluate the immunologic effect of anterior synechiae (AS) in a murine model of corneal transplantation. METHODS: Orthotopic penetrating keratoplasty with 12 interrupted sutures was performed on C57BL/6 donor mice and BALB/c recipient mice without AS (AS- group). In contrast to suturing in the AS- group, 3 of the 12 sutures were placed to create AS (AS+ group). The average graft opacity scores and rejection rates of both groups were compared. Cytotoxic T-lymphocyte (CTL) reactions and delayed hypersensitivity (DH) were evaluated 3 weeks after transplantation. Corneal cytokine expression was evaluated. RESULTS: The opacity scores of the AS+ group were consistently greater than those of the AS- group, and the rejection rate of the AS+ group was significantly greater than that of the AS- group (86% versus 54%, P = 0.03). The AS+ group had significantly higher CTL activity compared with the AS- group. There was no significant difference in DH between the two groups. The cytokine expression pattern in the AS+ group became similar to that of the AS- group in which the grafts were rejected. CONCLUSIONS: These findings indicate that AS impairs ocular immune privilege by mediating CTL activity, but without intensifying the DH response. Therefore, AS is a critical risk factor in allograft rejection in a murine model of corneal transplantation.

Animals↗

Cytokine profiles of aqueous humor and graft in orthotopic mouse corneal transplantation.

BACKGROUND: Cytokine profile is a key in understanding the mechanisms of allograft rejection. Cytokine expression in the aqueous humor and the correlation between the aqueous humor cells and corneal infiltrating cells are not fully understood in corneal transplantation. METHODS: Orthotopic mouse corneal transplantation was performed using BALB/c (H2d) mice as recipients, and C3H/He (H2k) and BALB/c mice as donors for allografts and isografts, respectively. Immunocytochemistry was performed on aqueous humor cells. Corneal graft was studied immunohistochemically. Cytokine gene expressions of the cells infiltrating the aqueous humor and corneal grafts were determined by the semiquantitative reverse transcription and polymerase chain reaction method. RESULTS: Interferon-gamma, interleukin (IL)-2, IL-4, and IL-10 were detected in the cells infiltrating the aqueous humor and corneal grafts at both the protein and gene expression levels. T helper 1 (Th1) cytokine expressions at the protein level, however, were consistently predominant in the rejected allografts compared to those of Th2 cytokines. The cytokine and surface marker profiles of the cells in the aqueous humor corresponded well to those of the cells infiltrating the corneal grafts. Cytokine protein and mRNA expression levels in the aqueous humor decreased rapidly. CONCLUSIONS: Allorejection in corneal transplantation is Th1 cytokine-predominant. Infiltrating cells do not express Th2 cytokine so much in allograft rejection, as compared with Th1 cytokine. The cell infiltration patterns of the aqueous humor were well correlated with those of the cornea.

Animals↗

Three-dimensional organization of collagen fibrils during corneal stromal wound healing after excimer laser keratectomy.

PURPOSE: To investigate the structural changes in corneal stromal collagen fibrils after excimer laser keratectomy in relation to the degree of corneal haze. SETTING: University of Tokyo Hospital, Tokyo, Japan. METHODS: Corneal haze was quantitatively measured by analyzing the light scattering in Scheimpflug images of the corneas of white rabbits after excimer laser keratectomy. Collagen fibril structure was examined using scanning electron microscopy after chemical digestion with sodium hydroxide solution; the same specimens were examined by transmission electron microscopy after re-embedding. RESULTS: Corneal haze reached a peak 4 weeks after excimer laser keratectomy and then gradually decreased. The collagen fibrils of the normal cornea were regularly arranged parallel to the surface of the cornea, with small interfibrillar distances. After excimer laser keratectomy, the arrangement was highly disordered, with increased interfibrillar distances. These structural changes were most prominent 4 weeks after excimer laser keratectomy. CONCLUSION: The structural changes in the collagen fibrils of the corneal stroma, especially the increase in interfibrillar distances and the disordered arrangement, were associated with corneal haze after excimer laser keratectomy.

Animals↗

Extracellular matrix production regulation by TGF-beta in corneal endothelial cells.

PURPOSE: Production of extracellular matrix (ECM) by corneal endothelial cells is related to physiologic functions and pathologic conditions and is regulated by many cytokines, including transforming growth factor-beta (TGF-beta). In this study, the molecular mechanism of ECM production regulation by TGF-beta was investigated in cultured corneal endothelial cells. METHODS: The production of ECM components (laminin and fibronectin) was detected in cultured corneal endothelial cells by western blot analysis. To determine the signal transduction pathways, mutant TGF-beta type I receptor (TbetaR-I) and/or Smad protein family members (intracellular signal transducers in TGF-beta signaling) were overexpressed by transfecting their cDNA into the cultured cells, and the effects on ECM production were observed. RESULTS: The production of laminin and fibronectin was stimulated by treatment with TGF-beta1 or TGF-beta2. After transient transfection of cDNA of the constitutively active (CA) mutant of TbetaR-I, the production of laminin and fibronectin was stimulated even in the absence of TGF-beta. The transfection of the dominant negative mutant of TbetaR-I counteracted the effects of TGF-beta. These results confirm that TGF-beta directly stimulates ECM production from corneal endothelial cells through TbetaR-I. The ECM production stimulation by TGF-beta or CA TbetaR-I was accelerated by the overexpression of Smad2, Smad3, and/or Smad4 and inhibited by that of Smad7. These results show that TGF-beta signals connected to ECM production are regulated by Smad family members, located downstream of TbetaR-I. CONCLUSIONS: The results of this study show that TGF-beta stimulates ECM production from corneal endothelial cells through TbetaR-I and Smad family transducers.

Animals↗

Genome organization of human 48-kDa oligosaccharyltransferase (DDOST).

The enzyme oligosaccharyltransferase (dolichyl-diphosphooligosaccharide-protein glycosyltransferase; EC 2. 4.1.119) (DDOST) catalyzes the transfer of a high-mannose oligosaccharide (GlcNac2Man9Glc3) from a dolichol-linked oligosaccharide donor (dolichol-P-GlcNac2Man9Glc3) onto the asparagine acceptor site within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains across the membrane of the endoplasmic reticulum. We isolated mouse and human DDOST cDNAs from retinoic acid-treated mouse P19 EC cells and human NT-2 cells, respectively. DDOST mRNA is expressed intensely in heart and pancreas, but at lower levels in brain. Here we show that the human DDOST 48-kDa subunit gene (HGMW-approved symbol DDOST) is organized into 11 exons expanding about 9 kb. This DDOST subunit gene is localized on chromosome 1p36.1 by fluorescence in situ hybridization analysis.

Amino Acid Sequence↗

Role of Fas-Fas ligand interactions in the immunorejection of allogeneic mouse corneal transplants.

BACKGROUND: The expression of Fas ligand (FasL) in the eye has been proposed to be an important component of ocular immune privilege. Since the unusually favorable outcome of corneal transplantation is thought to result from the immune privilege of the eye, examination of the function of FasL on corneal allografts would be a test of that hypothesis. METHODS: To investigate the role of Fas-FasL interaction in corneal allografts, orthotopic corneal transplantation was performed using C57BL/6 (B6, FasL+) and B6-gld (FasL-) mice as cornea donors and BALB/c mice as recipients. The rejection rate of B6-gld grafts (FasL- group) was compared with that of normal B6 control corneas. RESULTS: The rejection rate at the final observation (8 weeks) in the FasL- group (89%) was significantly higher than in the FasL+ control group (47%). FasL expression was found on the corneal endothelium by staining with anti-FasL monoclonal antibodies. The TdT-mediated dUTP nick-end labeling assay revealed that apoptotic cells were attached to the endothelium in the control group but not in the FasL- groups. CONCLUSIONS: Apoptosis of infiltrating cells on the corneal endothelium resulting from Fas-FasL interaction plays an important role in the high success rate of corneal transplantation.

Animals↗