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Biomedical subjects

S Sugai

Publications and source records attributed to S Sugai.

At least 73 records · Page 4Linked to original sources
PubMed1997

[Intraocular neovascularization].

To investigate the mechanism of intraocular neovascularization, we studied how vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) are expressed in the ocular tissues under hypoxic conditions. Prior to proliferation of vascular endothelial cells resulting in neovascularization, the retinal tissues such as pericytes, retinal glial cells, ganglion cells, and ciliary epithelium react directly to hypoxia expressing VEGF and/or IL-8 and stimulate endothelial cell proliferation in a paracrine manner. We demonstrated that transcription factor activator protein-1 (AP-1) is activated for expression of VEGF messenger ribonuculeic acid (mRNA) and in a similar way nuclear factor kappa B (NF-kappa B) is activated for expression of IL-8 mRNA. However, hypoxia-induced expression of VEGF and/ or IL-8 is only one aspect of the complicated processes in intraocular neovascularization. We hope that further detailed analysis of the mechanism will make it possible to inhibit and treat clinically intraocular neovascularization in the near future.

Adult↗
PubMed1997

[Long-term follow-up of 43 patients with Sjögren's syndrome].

OBJECTIVE: To study the long-term outcome in patients with Sjögren's syndrome (SS). METHODS: We retrospectively studied a cohort of 43 patients with SS; 31 patients with primary SS and 12 patients with secondary SS (6 patients with rheumatoid arthritis, 3 patients with mixed connective tissue disease, 2 patients with systemic lupus erythematosus and 1 patient with systemic sclerosis). Follow-up assessments were performed for 10-20 years following the initial diagnosis. RESULTS: During follow-up, 29 patients (67%) with SS developed new extraglandular manifestations including: a small amount of monoclonal gammopathy (10 patients), interstitial pulmonary disease (8 patients), malignancy (4 patients developed cancer, 1 patient developed malignant lymphoma), Raynaud's phenomenon (4 patient), peripheral neuropathy (3 patients), renal disease (2 patients), myopathy (2 patients) and others. Statistically significant differences in the salivary gland scintigraphy existed between the progressed group and the stable group at both the initial diagnosis and ten years later. Patients with anti-Ro (SS-A) antibody had a high incidence of salivary gland enlargement, hypocomplementemia, rheumatoid factor and anti-nuclear antibody. The focus scores of the labial salivary biopsy in anti-La (SS-B) antibody positive patients were significantly higher than in patients without this antibody. No statistically significant differences were noted in symptoms and signs between study entry and follow-up. CONCLUSIONS: Although sicca symptoms involving the eyes and the mouth did not progress in most of SS patients, 67.4% of SS patients developed new extraglandular manifestations during the 10-20 years follow-up period.

Adult↗
PubMed1996

The burst-phase intermediate in the refolding of beta-lactoglobulin studied by stopped-flow circular dichroism and absorption spectroscopy.

The kinetics of the guanidine hydrochloride-induced unfolding and refolding of bovine beta-lactoglobulin, a predominantly beta-sheet protein in the native state, have been studied by stopped-flow circular dichroism and absorption measurements at pH 3.2 and 4.5 degrees C. The refolding reaction was a complex process composed of different kinetic phases, while the unfolding was a single-phase reaction. Most notably, a burst-phase intermediate of refolding, which was formed during the dead time of stopped-flow measurements (approximately 18 ms), showed more intense ellipticity signals in the peptide region below 240 nm than the native state, yielding overshoot behavior in the refolding curves. We have investigated the spectral properties and structural stability of the burst-phase intermediate and also the structural properties in the unfolded state in 4.0 M guanidine hydrochloride of the protein and its disulfide-cleaved derivative. The main conclusions are: (1) the more intense ellipticity of the intermediate in the peptide region arises from formation of non-native alpha-helical structure in the intermediate, apparently suggesting that the folding of beta-lactoglobulin is not represented by a simple sequential mechanism. (2) The burst-phase intermediate has, however, a number of properties in common with the folding intermediates or with the molten globule states of other globular proteins whose folding reactions are known to be represented by the sequential model. These properties include: the presence of the secondary structure without the specific tertiary structure; formation of a hydrophobic core; broad unfolding transition of the intermediate; and rapidity of formation of the intermediate. The burst-phase intermediate of beta-lactoglobulin is thus classified as the same species as the molten globule state. (3) The circular dichroism spectra of beta-lactoglobulin and its disulfide-cleaved derivative in 4.0 M guanidine hydrochloride suggests the presence of the residual beta-structure in the unfolded state and the stabilization of the beta-structure by disulfide bonds. Thus; if this residual beta-structure is part of the native beta-structure and forms a folding initiation site, the folding reaction of beta-lactoglobulin may not necessarily be inconsistent with the sequential model. The non-native alpha-helices in the burst-phase intermediate may be formed in an immature part of the protein molecule because of the local alpha-helical propensity in this part.

Circular Dichroism↗
PubMed1996

High prevalence of B-cell monoclonality in labial gland biopsies of Japanese Sjögren's syndrome patients.

Patients with Sjögren's syndrome (SS) have an increased risk of developing malignant lymphoma. Although some clinical parameters may herald the imminent onset of lymphoma, few reliable markers are available to predict the progression to a malignant lymphoproliferative disorder. Although there are a number of immunological and serologic features that distinguish SS in Japanese patients, in common with their Western counterparts these patients also have an increased risk of lymphoid neoplasia. Recently we have reported finding a high prevalence (17%) of monoclonal immunoglobulin (Ig) heavy chain gene rearrangements in labial salivary gland (LSG) biopsies of Western SS using the polymerase chain reaction (PCR). In many cases this finding was predictive for the subsequent development of lymphoma. In this study LSG from 50 Japanese SS patients were examined for Ig heavy chain gene monoclonality using PCR to amplify the VDJ region and identified in 7 of 50 (14%) cases. Three patients with monoclonality in the LSG had evidence of lymphoma at extra-salivary gland sites. In one of these the diagnosis of lymphoma was made subsequent to lip biopsy. In the other two lymphoma at extra-salivary gland sites was diagnosed prior to LSG biopsy. The results suggest that the prevalence of Ig heavy chain gene monoclonality in LSG of Japanese SS patients is similar to that in the West, and that neoplastic cells can be identified in LSG as a component of more widely disseminated disease.

Aged↗
PubMed1996

Expanded polyglutamine in the Machado-Joseph disease protein induces cell death in vitro and in vivo.

Recently, we identified a novel gene, MJD1, which contains an expanded CAG triplet repeat in Machado-Joseph disease. Here we report the induction of apoptosis in cultured cells expressing a portion of the MJD1 gene that includes the expanded CAG repeats. Cell death occurs only when the CAG repeat is translated into polyglutamine residues, which apparently precipitate in large covalently modified forms. We also created ataxic transgenic mice by expressing the expanded polyglutamine stretch in Purkinje cells. Our results demonstrate the potential involvement of the expanded polyglutamine as the common aetiological agent for inherited neurodegenerative diseases with CAG expansions.

Animals↗
PubMed1996

A synthetic peptide study on the molten globule of alpha-lactalbumin.

We investigated the conformations of peptides that encompass the B helix or C helix region formed in the molten globule of bovine alpha-lactalbumin to get information on the molecular mechanism that stabilizes the molten globule. The CD spectra show that the isolated B and C helices are intrinsically unstable. The chemical shifts, NOE connectivities, and CD spectrum indicate that no helical structure is induced in the C helix region (86-99) by extending the peptide sequence to include the hydrophobic cluster region (101-107), although the hydrophobic cluster region can be regarded as a possible initiation site for folding of the protein. We also clarified that the isolated B helix (23-34) peptide does not directly interact with the C helix or hydrophobic cluster region. These results suggest that the B and C helices in the molten globule are stabilized by their interaction with other parts of the protein.

Amino Acid Sequence↗
PubMed1996

[Malignancy in autoimmune diseases].

Association between antecedent autoimmune diseases and malignancy, including lympho-proliferative disorders (LPD), has been reported in generalized autoimmune diseases such as systemic lupus erythematosus (SLE), dermatomyositis (DM) and rheumatoid arthritis (RA), and also in organ-specific autoimmune diseases such as Sjögren's syndrome (SS) and chronic thyroiditis. In this paper, LPD were summarized for DM, SLE, RA and SS, and some etiologic factors were considered. In surveying previous Japanese literature on the topic, it was revealed that LPD occur frequently in DM similar to various types of cancer. The period between the occurrence of cancer and DM is usually within 12 months, suggesting that the etiologic factor may differ between cancer and LPD in DM. Sixty one cases (20.0%) of monoclonal non-malignant LPD were observed among our 306 patients with SS. Fifteen cases (5.0%) of malignant LPD such as malignant lymphomas (13 cases) and Waldenström's macroglobulinemias (2 cases) were also seen among our SS patients. The activation of rheumatoid factor genes such as Humkv 325 and Vg was considered as one of the triggering factors to advance LPD from the benign to malignant state. A high amount of the bcl-2 protein expression was detected in lymphoepithelial lesions of salivary glands in patients with SS, suggesting that the activation of this gene plays an important role in the progression of the lesion from benign to malignant LPD. Accumulation of many genetic abnormalities including bcl-2 and p 53 genes by chronic stimulation of T and B cells at the site of the autoimmune reaction may be important in the high occurrence of LPD in patients with autoimmune diseases.

Autoimmune Diseases↗
PubMed1996

[Rheumatoid factor idiotypes in patients with Sjögren's syndrome].

Sjögren's syndrome (SS) is a systemic as well as an organ-specific autoimmune disease, characterized by multiple organ damages, autoantibody production such as rheumatoid factor (RF), and also by the development of lymphoproliferative disorders such as monoclonal gammopathy or malignant lymphoma. We produced two monoclonal anti-idotypic (ld) antibodies (A-SF 18/2 and A-AMB 1/5) against monoclonal RFs (IgA-L and IgM-K) derived from patients with SS. Expression of the cross-reactive idiotype (CRI) of these monoclonal RFs was studied in 101 patients with SS, 71 with rheumatoid arthritis (RA) without complication of SS and 93 normal subjects. The results showed the followings: (1) By the enzyme-linked immunosorbent assay (ELISA), 17.8% and 15.8% of patients with SS and 15.5% and 21.7% of patients with RA showed CRI of SF 18/2 and AMB 1/5, respectively, whereas 6.5% and 5.7% of normal subjects showed these CRIs, respectively, (2) In the SF 18/2 Id system, there was one group (45%) in SS patients who showed weak positive CRI, whereas there was no such group in the AMB 1/5 Id system, (3) Out of 15 patients with SS, there were 4 patients whose peripheral blood lymphocytes had a significant amount of surface membrane Id of SF 18/2 (9.1-37.7%), suggesting the existence of a monoclonal population in the blood. These data suggest that clones with one particular SF 18/2 Id were markedly activated in SS patients and these may be related to the monoclonal proliferation of RF Id-positive B cells in patients with SS.

Antibodies, Anti-Idiotypic↗
PubMed1996

[Monoclonal rheumatoid factor in a patient with multiple myeloma after chemotherapy].

A patient with multiple myeloma was treated with several cycles of chemotherapy and developed monoclonal IgA rheumatoid factor. The monoclonal rheumatoid factor in this case reacted with 2 types of monoclonal antiidiotypic antibody derived from monoclonal rheumatoid factors in a patient with Sjögren's syndrome and a patient with macroglobulinemia. Two possible mechanisms accounting for the development of rheumatoid factor activity during a course of chemotherapy are discussed. The first possibility is that the rheumatoid factor or activity had been initially covered by an antiidiotypic antibody but was disclosed by the decreased production of this antibody following by the immunosuppressive therapy. The second possibility is that monoclonal IgA acquired rheumatoid factor activity by a point mutation resulting in a change in the molecular structure of the idiotype.

Aged↗
PubMed1996

[A case of Sjögren's syndrome with an eyelid tumor, a so-termed pseudolymphoma of the iacrimal gland].

The female subject, 64 years old, subjectively noticed a mild dryness of the eyes and bilateral, submandibular swelling in 1988. The clinical symptom was mild, and such autoantibody and hyper-gammaglobulinemia as often observed in Sjögren's syndrome were not recognized. However, by judging from the results of gum test (9 mL/10 min), salivary gland scan (Grade 2) and the labial biopsy, we diagnosed the case as Sjögren's syndrome. We then administered prednisolone at 40 mg at the onset of treatment and gradually decreasing the dosage over 3.5 years, and the symptoms improved. As an eyelid tumor in the left eye was noticed in 1991 and began to enlarge, the subject was hospitalized in June of 1992. The biopsy of the tumor (2.0 x 1.7 cm) showed marked polyclonal lymphoproliferation with lymphoid follicles which was determined by immunohistological staining. The case was a patient with a lymphoproliferative lesion from a lacrimal gland which is equal to a so-termed pseudolymphoma. Since there are some reports concerning the transition from pseudolymphoma to malignant lymphoma, this patient should be followed carefully.

Eyelid Neoplasms↗
PubMed1995

Inhibition of skin development by targeted expression of a dominant-negative retinoic acid receptor.

Although pharmacological doses of retinoic acid (RA) have a wide variety of actions in vivo, experimental difficulties have prevented a definitive assignment of its physiological functions. We recently made a dominant-negative retinoic acid receptor (RAR) by a single amino-acid substitution which creates a dominant-negative thyroid hormone receptor. The mutated RAR efficiently inhibited the endogenous activities of RARs (alpha, beta, gamma). Thus, targeted expression of the mutated receptor should reveal RA functions during organogenesis by blocking RA signalling in the tissues concerned. To address this possibility, we expressed the dominant-negative RAR in the epidermis, a potential target organ of RA. We report here that the resultant transgenic mice exhibited dramatic suppression of epidermal maturation, demonstrating the requirement of RA in normal skin development.

Animals↗
PubMed1995

The superreactive disulfide bonds in alpha-lactalbumin and lysozyme.

The disulfide reduction kinetics in equine lysozyme (ELZ), which is a Ca(2+)-binding lysozyme, and human (HLA) and equine alpha-lactalbumin (ELA) at pH 8.5 and 25 degrees C by excess dithiothreitol were studied, and it was found that in ELZ there is no superreactive disulfide bond, while one of the disulfides is reduced very quickly by the reducing agent in HLA and ELA, as in bovine alpha-lactalbumin. The local conformation around the surface disulfide in ELZ seems to be more similar to that in hen egg-white lysozyme than in alpha-lactalbumin. The four disulfides in ELZ were reduced slowly in an apparently single-exponential form, and the bound Ca2+ lowered the reduction rate. The torsion energy on each of the disulfides in three alpha-lactalbumin and eight c-type lysozymes whose native conformations have been experimentally or theoretically analyzed was calculated, and it was found that torsion imposed on the surface disulfide between Cys 6 and Cys 120 in alpha-lactalbumin is a main cause of the superreactivity and all of lysozymes, including the Ca(2+)-binding ones, have no such strained surface bond.

Animals↗
PubMed1995

Detection of proteoglycans in human posterior capsule opacification.

Using cuprolinic blue staining, we histochemically examined the ultrastructural localization of proteoglycans in the fibrous-type human posterior capsule opacification. This capsule opacification contained proteoglycans that showed positive staining with cuprolinic blue. Many cuprolinic-blue-positive filaments were present within the bundles of collagen fibrils, basal lamina-like material and basal lamina of proliferated lens epithelial cells. Pretreatment with enzymes and nitrous acid revealed that the collagen fibrils contained chondroitin sulfate and dermatan sulfate, whereas the basal lamina-like material and basal lamina of epithelial cells contained heparan sulfate. These results suggest that proteoglycans are one of the components in posterior capsule opacification.

Aged↗
PubMed1995

Relationship between intraocular pressure and age in the exfoliation syndrome.

We examined the presence or absence of exfoliative material and measured the intraocular pressure (IOP) of 220 residents of a nursing home. The prevalence of the exfoliation syndrome increased with age and the IOP of persons with the exfoliation syndrome was higher than that of persons without the syndrome. In eyes with the exfoliation syndrome, the IOP had a tendency to decrease with increasing age. Aging had little influence on IOP in eyes without the exfoliation syndrome. There were significant differences between the two groups with regard to the effects of aging on IOP.

Aged↗