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Biomedical subjects

S Sugai

Publications and source records attributed to S Sugai.

At least 91 records · Page 5Linked to original sources
PubMed1995

[Clinical aspects and types of Sjögren's syndrome].

Sjögren's syndrome (SS) is a systemic as well as an organ-specific autoimmune disease, characterized by destructive lymphocytic infiltration of the salivary and lacrimal glands. We divided SS patients into three stages: stage I is glandular SS, stage II is extraglandular SS, and stage III is extraglandular SS with lymphoid malignancy. The lymphoaggressive nature of the disease appears to lead SS patients from stage I to II and from stage II to III. However, stage III patients made up only 5% of SS patients. Many patients remain stable in stages I or II for as long as 10 or 20 years. Therefore, we can assume that there are factors which trigger patients in stages I or II to progress to stages II or III and that only those patients who have such factors progress from stages I or II to stages II or III, respectively. Accumulation in the salivary glands or in the peripheral blood of B cells which have rearrangement of the RF-related germline gene Vg or over-expression of the bcl-2 gene in the lymphoepithelial lesion might be included among these factors.

Adolescent↗
PubMed1995

[Sjögren's syndrome as a lymphoaggressive disorder; bcl-2 expression in lymphocytes infiltrated in salivary glands].

Sjögren's syndrome (SS) is a unique disease which develops a high incidence of lymphoproliferative disorder such as monoclonal gammopathy or malignant lymphoma. In order to elucidate the mechanism of the progression from polyclonal to monoclonal lymphoproliferation in SS patient, we analyzed the monoclonal nature and the expression of bcl-2 protein in the salivary glands. Formalin-fixed, paraffin-embedded salivary gland (labial salivary glands, 45; parotid glands, 6; submaxillary glands, 1) tissues or lung tissues (interstitial pneumonia in 2 patients with SS) were serially sectioned and evaluated using the standard avidin-biotin-peroxidase (ABC) technique. Murine monoclonal primary antibodies obtained from Dakopatts to B-cells (L26; CD20) and T-cell markers (UCHL1; CD45RO) and bcl-2 protein were employed. The bcl-2-positive areas were stained with T and B cell markers in serially sectioned specimens. Lymphocytes forming the LEL were mostly composed of CD20-positive B-cells and these cells expressed bcl-2 protein. In the lip biopsy specimens, 36 of 45 patients showed small areas of bcl-2 expression in periductal lymphocytes. The expression of bcl-2 protein in the cells plays a crucial role in the cells escaping apoptotic cell death, living long and resulting in autoantibody production, and obtaining the increased risk of monoclonal proliferation of the cells. These findings provide further evidence for understanding the mechanism of monoclonal transformation from polyclonal lymphoproliferation in autoimmune reaction.

Autoimmunity↗
PubMed1995

[Lymphoproliferative disorders in patients with Sjögren's syndrome--Vg gene rearrangement and expression of bcl-2 protein].

Sjögren's syndrome (SS) is a unique disease which develops a high incidence of lymphoproliferative disorders (LPD) such as monoclonal gammopathy or malignant lymphoma. In order to elucidate the mechanism responsible for the emergence of monoclonal B cell proliferation at the site of a chronic autoimmune reaction, the rheumatoid factor (RF) related germline gene Vg and expression of the bcl-2 gene in the lymphoepithelial lesion (LEL) were studied. Predominant usage of the Vg or Vg-like genes was found in the peripheral blood leukocytes in SS patients and abundant expression of bcl-2 protein in the lymphocytes in and around the LEL were observed. These results suggest that RF clones were activated resulting into monoclonal proliferation and overexpression of bcl-2 protein play a role allowing the cell to escape a apoptotic cell death resulting into the increased risk of monoclonal proliferation in SS patients.

Female↗
PubMed1994

Chronic active hepatitis in transgenic mice expressing interferon-gamma in the liver.

Interferon-gamma may play an important role in the immune response and in inflammatory diseases, including chronic active hepatitis. To understand the role of interferon-gamma in the regulation of inflammation and to establish a mouse model of chronic active hepatitis, we produced transgenic mice in which the mouse interferon-gamma gene was regulated by a liver-specific promoter, the serum amyloid P component gene promoter. Four transgenic mouse lines were generated, and two of these lines expressed mRNA of interferon-gamma in the liver. Levels of serum transaminases increased gradually as a function of age and were significantly higher than those of interferon-gamma-negative littermates after 4 weeks after birth. One transgenic mouse line showed a histology of chronic active hepatitis similar to that found in human patients, although cirrhotic changes such as fibrosis were scarce. Thus, the liver-specific production of interferon-gamma is sufficient to induce chronic inflammatory disease and this mouse is a transgenic model of chronic active hepatitis.

Alanine Transaminase↗
PubMed1994

Rearrangement of the rheumatoid factor-related germline gene Vg and bcl-2 expression in lymphoproliferative disorders in patients with Sjögren's syndrome.

Of 250 patients with Sjögren's syndrome (SS) (190 with 1 degree SS and 60 with 2 degrees SS), 60 patients demonstrated lymphoproliferative disorders (LPD): 41 patients had monoclonal gammopathy (MG), 4 had pseudolymphoma, 3 had in situ monoclonal lymphoproliferation, and 12 had malignant lymphoma. Rearrangement of the rheumatoid factor (RF)-related germline gene Vg (associated with the monoclonal RF SF18/2) was demonstrated in 24 of 50 genomic DNAs from the peripheral blood leukocytes of SS patients. It was found in none of 20 DNAs from normal subjects. This suggests an almost 50% incidence of a germline Ig gene rearrangement in SS patients without clinical MG. Lymphocytes composing the lymphoepithelial lesion (LEL) in the major salivary glands of SS patients expressed the oncogene bcl-2 protein in 4 out of 6 patients. The progression of SS from benign to malignant lymphoproliferation may be related to suppression of apoptotic death by bcl-2. These findings suggest that (i) RF clones are activated in SS with little or no somatic mutation resulting in monoclonal proliferation and (ii) the LEL in the salivary gland is one site for monoclonal B cell proliferation and emerging malignant lymphoma.

Adult↗
PubMed1994

Conformational comparison between alpha-lactalbumin and lysozyme.

Comparisons of the conformation behavior between LA and LZ (especially BLA and HEL) are described, which have contributed to the development and understanding of the molten globule folding intermediate of protein. BLA (and other LAs) is clearly a very good model protein for fundamental studies of molten globule protein conformation and the mechanism of protein unfolding/folding in vitro. Our work for about 20 years, on the conformational characterizations of proteins in the LA-LZ family, primarily based on macroscopic observations, led to three important findings: 1) equilibrium intermediate of unfolding/folding of LA is in the molten globule state, as assumed later for many proteins; 2) kinetic (transient) folding intermediates of BLA and HEL are the same as the equilibrium intermediate of BLA, and they include the framework remaining in the N state; and 3) the bound Ca2+, which is the main factor explaining the apparent difference in the conformational behavior between BLA and HEL, is found in some LZs. The conformational characterization of two Ca(2+)-binding LZs (ELZ and PLZ) by CD, calorimetry, X-ray, and NMR structural analysis is shown in detail and the mechanism of molecular evolution is discussed for the LA-LZ family. However, first concept of the molten globule has gradually changed with the definition of the collapsed form, the N-like or the U-like molten globule and so on, based on the results of measurements at residual resolutions including X-ray, NMR, and isotope exchange of some proteins. Our recent data on such microscopic measurements of LAs in the molten globule state are therefore compared with those of various proteins by other researchers. The roles of the disulfide bonds to stabilize the molten globule state are also discussed with our conformational research results on disulfide-reduced BLA. It is hoped that the multidimensional-NMR can be used for the 3D structural analysis of proteins in the LA-LZ family in the U, I, and N states in the solutions, and that our conformational work on the proteins done in vitro can be applied to understand the conformational events of proteins in vivo.

Amino Acid Sequence↗
PubMed1994

Sweet's syndrome during therapy with granulocyte colony-stimulating factor in a patient with aplastic anaemia.

A patient with aplastic anaemia developed Sweet's syndrome (a febrile neutrophilic dermatosis) during granulocyte colony-stimulating factor (G-CSF) therapy. Three repeated episodes of appearance and disappearance of erythematous nodules after administration and withdrawal of G-CSF confirmed that G-CSF induced Sweet's syndrome in the patient. Sweet's syndrome has been reported in patients with myelodysplastic syndrome and acute leukemia, but not in patients with aplastic anaemia. This is the first report of a patient with aplastic anaemia who developed G-CSF-induced Sweet's syndrome.

Adult↗
PubMed1994

Prevalence of HBV and HCV infection in Japanese patients with hepatocellular carcinoma.

The prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection was investigated in 63 Japanese patients with hepatocellular carcinoma (HCC). HBV infection was confirmed by measuring hepatitis B surface antigen and HBV-DNA in the serum, and HCV infection was confirmed by measuring antibody to HCV using a 2nd generation test and HCV-RNA in serum. Some 54.0% of the patients had HCV infection only, 27.0% had HBV infection only, and 9.5% had both HCV and HBV infection. Only 9.5% of HCC patients had neither HCV nor HBV markers. These results indicate that, in Japan, HCV and HBV infection is an important factor associated with HCC, and that the hepatitis virus may have a role in the carcinogenesis of HCC.

Adult↗
PubMed1994

[Successful VEP-IFN-alpha therapy in a case of non-secretory plasma cell leukemia (BJ-kappa type)].

Plasma cell leukemia is a rare disorder with poor prognosis. We present a case of non-secretory primary plasma cell leukemia (Bence-Jones kappa type), which was treated successfully by VEP-IFN-alpha therapy. A 82-year old man was admitted to Kanazawa Medical University in May 1991, because of emaciation and dehydration. Clinical findings showed decreased level of gamma-globulin (IgG, IgA and IgM were all decreased markedly), hypercalcemia, renal dysfunction and increased serum beta-2 microglobulin. The peripheral blood leukocyte count was 30,100/microliters with 64% plasma cells, and 80.4% plasma cells were also observed in the bone marrow. Only light chain-kappa was detected in plasma cells by an immunohistochemical staining method, but immunoelectrophoresis showed no M-bow either in serum or urine. Electron microscopy revealed typical plasma cells with prominently developed rough endoplasmic reticulum. From these results, the diagnosis of non-secretory primary plasma cell leukemia was established. He was treated with VEP-IFN-alpha regimen, and plasma cells decreased markedly in both peripheral blood and bone marrow. Serum immunoglobulin recovered to within the normal range. After 6 courses of VEP-IFN-alpha, complete remission was achieved and the remission was maintained until he died of an unrelated event, bronchial obstruction due to misswallowing, in April 1992.

Aged↗
PubMed1993

Unfolding of the molten globule state of alpha-lactalbumin studied by 1H NMR.

The urea-induced unfolding of the molten globule state of bovine alpha-lactalbumin was investigated by 1H nuclear magnetic resonance. In the molten globule state, most of the aromatic resonances deviate from their random coil values, indicating that aromatic side chains form some ordered structures in the molten globule state. When the urea concentration increases, the resonances are shifted, and the deviations from the random coil values are diminished. Because the chemical shifts of several random coil peptides are found to be independent of urea concentration, the urea-induced shifts of the resonances in the molten globule state reflect the unfolding transition of some ordered structures. The unfolding transitions measured by individual aromatic resonances do not coincide with each other. The unfolding transition curves obtained from some aromatic resonances are also different from those of the secondary structures measured by circular dichroism spectra. These results clearly show that the unfolding of the molten globule state of alpha-lactalbumin is not a cooperative two-state process.

Animals↗
PubMed1993

Secondary structure of globular proteins at the early and the final stages in protein folding.

The ellipticities for an early transient intermediate in refolding observed by kinetic circular dichroism measurements at 220-225 nm for 14 different proteins are summarized, and the ellipticity values are compared with those for the final native proteins and also with the ellipticities expected from a physical theory of protein and polypeptide secondary structure. The results show that a substantial part of the protein secondary structure is in general formed in the earliest detectable intermediate in refolding and that the ellipticities in both the native and the intermediate states are consistent with the physical theory of protein secondary structure.

Animals↗
PubMed1993

Anterior capsule opacification in monkey eyes with posterior chamber intraocular lenses.

OBJECTIVE: To examine the morphologic features of anterior capsule opacifications in pseudophakic monkey eyes. METHODS: Extracapsular lens extraction with implantation of posterior chamber intraocular lenses in six monkey eyes. Eyes were enucleated 2, 4, and 12 months after implantation and then studied with light and electron microscopy. Distribution of proteoglycans was also examined with cuprolinic blue staining. RESULTS: Anterior capsule opacifications were composed of proliferated cellular and extracellular matrix components situated between the anterior capsule and the optics of the intraocular lens. The morphologic features of the proliferated cells were consistent with epithelial cells, and these cells probably represented lens epithelial cells. The extracellular matrix, which consisted of collagen fibrils, basal lamina-like material, and microfibrils, was most prominent in the specimens obtained 12 months after lens implantation. The extracellular matrix contained proteoglycans that showed positive staining with cuprolinic blue. CONCLUSIONS: Anterior capsule opacifications consisted of proliferated lens epithelial cells and aberrant extracellular matrix.

Animals↗
PubMed1993

[Clinical usefulness of newly developed urine protein dipstick (URINE-TP)].

We assessed the clinical usefulness of a newly developed urine protein dipstick (URINE-TP; U-TP) which can detect gamma-globulin and other proteins as well as albumin. Semiquantitative values of urine protein evaluated with U-TP were compared with those evaluated with ordinary urine protein dipsticks (BM-TEST) in 966 urine samples. The two tests showed the same semiquantitative values in 572 of 966 samples (59.2%; Group A). However, U-TP showed a more positive reaction two gradations higher in 89 samples (9.2%; Group B), and showed a more positive value with one gradation higher in 283 samples (29.3%; Group C) compared with BM-TEST. We then measured total protein, alpha 1-microglobulin (alpha 1-M), NAG and beta 2-microglobulin (beta 2-M) in urine, and serum beta 2-M, urea nitrogen (UN) and creatinine (CRE) in both Group A and Group B. In BM-TEST negative patients, urinary total protein, tubular proteins (alpha 1-M, beta 2-M) and NAG were significantly higher (p < 0.01) in Group B than in Group A. Moreover, among patients who had trace or positive results by BM-TEST, serum UN was significantly higher (p < 0.01) in Group B than in Group A. These results suggest that U-TP, a newly developed urine protein dipstick, can detect tubular proteins which cannot be detected by ordinary dipsticks. U-TP may be useful for early detection of renal tubular damage, especially when use is the combined with conventional dipsticks.

Acetylglucosaminidase↗
PubMed1993

[A case of Sjögren's syndrome at the age of 91 with a lymphoepithelial lesion].

A 91 year old woman with Sjögren's syndrome who developed a lymphoepithelial lesion and showed an active state of the disease is described. Since June, 1990, the patient had been complaining of dry eyes and mouth and a left submandibular tumor (1.0 x 1.5 cm in diameter). A biopsy of the tumor revealed lymphoepithelial lesions in the salivary gland. Mild anemia (Hb 9.6 g/dl) and an elevated erythrocyte sedimentation rate (80 mm/hr) were noted. The gamma-globulin level was 2.7 g/dl, IgG 2789 mg/dl, IgA 469 mg/dl, RAHA x80, antinuclear antibody x20, anti-SS-A x256, thyroid test x400 and microsome test x102400. The Schirmer's test showed decreased tear secretion (Lt. 3mm, Rt. 9mm) and keratoconjunctivitis sicca were noticed by an ophthalmologist. Salivary scintigraphy revealed decreased uptake and slow excretion of the isotope (grade II). A biopsy of a minor salivary gland showed periductal lymphocytic infiltration and acinar cell destruction. Immunohistochemical analyses revealed the cross-reactive idiotype of a monoclonal rheumatoid factor which is associated with a patient with Sjögren's syndrome, in the infiltrating lymphocytes and plasma cells of the minor salivary glands, but not in the lymphoepithelial lesions of the left submandibular gland. This was a rare case concerning a 91-year old patient with Sjögren's syndrome who developed a lymphoepithelial lesion and showed high activity in the serum and gives us valuable information on the relationship between aging and autoimmunity.

Aged↗
PubMed1993

[Histopathologic study of anterior capsule opacification in pseudophakic eyes].

We performed posterior chamber lens implantation (IOL) in three monkey eyes. All pseudophakic eyes developed a ring-shaped opacity, appearing on the IOL optics along the anterior capsule incision line. Transmission electron microscopic study revealed that the anterior capsule opacification was composed of proliferated cellular and extracellular components between the anterior capsule and the IOL optics. The proliferated cells looked like fibroblasts, but they were connected by desmosomes and covered by basal lamina. These histologic findings represented morphological features of epithelial cells, probably lens epithelial cells. Extracellular components consisted of collagen fibers, microfibrils, and basal lamina-like materials.

Animals↗