Biomedical subjects
Publications and source records attributed to Yasuo Suzuki.
Tris-bipyridine ruthenium-complexes carrying a disialo complex-type oligosaccharide were prepared via a one-pot transglycosylation using endo-glycosidase (Endo M); they bind to type-A influenza viruses with excellent affinity (IC50 = 8.4 microM), and their luminescence intensity is strongly depressed by virus-binding.
Four human pandemic influenza A virus strains isolated in 1957 and 1968, but not most of the epidemic strains isolated after 1968, possess sialidase activity under low-pH conditions. Here, we used cell-expressed neuraminidases (NAs) to determine the region of the N2 NA that is associated with low-pH stability of sialidase activity. We found that consensus amino acid regions responsible for low-pH stability did not exist in pandemic NAs but that two amino acid substitutions in the low-pH-stable A/Hong Kong/1/68 (H3N2) NA and a single substitution in the low-pH-unstable A/Texas/68 (H2N2) NA resulted in significant change in low-pH stability.
The Foxl1 gene, which encodes a winged helix transcriptional regulator, is expressed in the mesenchymal layer of developing and mature gastrointestinal tract. Foxl1-deficient mice exhibit various defects not only in the epithelial layer of the gastrointestinal tract but also in gut-associated lymphoid tissues. In the small intestine of Foxl1-deficient mice, the formation of Peyer's patches is affected, particularly in the caudal region. This alteration is shown to be due to the delayed formation of Peyer's patches organizing centers as revealed by the expressions of VCAM1 and IL-7 receptor alpha-chain at 17.5 days postcoitus. Peyer's patch defects are concordant with the significantly decreased expression of Lymphotoxin beta-receptor in the caudal region of fetal intestine. Foxl1 is suggested to regulate the responsiveness of fetal intestinal mesenchymal cells to inductive signals mediated by Lymphotoxins during Peyer's patch organogenesis. In addition, constitutive outgrowth of colonic patches due to defects in radioresistant stromal components of colonic patches are seen in Foxl1-deficient mice. Because of the functional similarities of hypertrophic colonic patches to those seen in hapten-induced experimental colitis, this hypertrophy is suggested to involve Lymphotoxin beta-receptor signaling. Together, the data suggest that Foxl1 might be involved in cellular responses of gut-associated lymphoid tissues dependent upon the Lymphotoxins/Lymphotoxin beta-receptor axis.
Pierisin-1, a cytotoxic protein found naturally in the cabbage butterfly, induces apoptosis of mammalian cells. Our recent studies suggest that pierisin-1 consists of an N-terminal ADP-ribosyltransferase domain, and a C-terminal region that binds to receptors on the surfaces of target cells and incorporates the protein into cells. The present study was undertaken to identify receptors for pierisin-1. The cross-linking and cloning experiments suggested that the proteins on cell membrane had no binding ability to pierisin-1. Inhibitory assays of fractionated lipids from human cervical carcinoma HeLa cells, which are highly sensitive to pierisin-1, indicated neutral glycosphingolipids on the cell surface to show receptor activity. Inhibitory assays and TLC immunostaining using anti-pierisin-1 antibodies demonstrated two neutral glycosphingolipids as active components. Analysis of their structures with glycosphingolipid-specific antibodies and negative secondary ion mass spectrometry identified them as globotriaosylceramide (Gb3) and globotetraosylceramide (Gb4). The receptor activities of Gb3 and Gb4 for pierisin-1 were also confirmed with these authentic compounds. Pierisin-1-insensitive mouse melanoma MEB4 cells were found to lack pierisin-1 receptors, including Gb3 and Gb4, but pretreatment of the cells with glycosphingolipid Gb3 or Gb4 enhanced their sensitivity to pierisin-1. Thus, Gb3 and Gb4 were proven to serve as pierisin-1 receptors. The C-terminal region of pierisin-1 consists of possible lectin domains of a ricin B-chain, containing QXW sequences, which are essential for its structural organization. Alteration of QXW by site-directed mutagenesis caused marked reduction of pierisin-1 cytotoxicity. Thus, our results suggest that pierisin-1 binds to Gb3 and Gb4 receptors at the C-terminal region, in a manner similar to ricin, and then exhibits cytotoxicity after incorporation into the cell.
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PURPOSE: To report the effect of high-dose intravenous corticosteroid pulse therapy with and without orbital radiotherapy on Graves' ophthalmopathy. DESIGN: Nonrandomized clinical trial. METHODS: We selected 39 Japanese patients (age range, 22-64 years; mean, 48 years; 31 women, 8 men) who had active Graves' ophthalmopathy among 195 consecutive patients. In the first 20 patients, high-dose intravenous methylprednisolone pulse therapy (1 g per day for 3 successive days, repeated 3 times within 3 weeks) followed by 24-Gy orbital radiotherapy was performed. In the other 19 of the 39 patients, high-dose intravenous methylprednisolone pulse therapy without orbital radiotherapy was performed. Coronal computed tomography (CT) of the orbit and exophthalmometry were performed before the corticosteroid pulse therapy, and 1 and 6 months after the corticosteroid pulse therapy. The maximum coronal section area of the most hypertrophic rectus muscle in each eye was measured based on orbital CT imaging. RESULTS: Clinical findings at study entry were not significantly different between the two groups. No significant difference was found in the maximum coronal section area of the most hypertrophic rectus muscle and the results of exophthalmometry measurements in both groups before the therapy. Extraocular muscle hypertrophy was significantly reduced 1 month and 6 months after the therapy (P < .01) in both groups. However, no beneficial therapeutic effect on proptosis was observed in either group at 1 month and 6 months after the therapy. No significant difference in the therapeutic effect on extraocular muscle hypertrophy and proptosis was found between the two groups. CONCLUSIONS: Orbital irradiation after corticosteroid pulse therapy had no beneficial therapeutic effects on rectus muscle hypertrophy or proptosis of active Graves' ophthalmopathy during the 6-month follow-up period.
PURPOSE: To confirm the idea that sole contraction of the superior oblique muscle causes attacks of superior oblique myokymia (SOM). DESIGN: Observational case report. METHODS: A 43-year-old man presented with episodic monocular oscillatory eye movements. Three-dimensional eye movements were recorded using the magnetic search coil system and analyzed as rotation vector. The attacks of SOM consisted of intorsional, depressive, and abductive fast phases and their exponential decaying slow phases. RESULTS: Average direction of rotation axis for the fast phases while fixating straight ahead was 51.5 +/- 5.4 degrees from depression axis in vertical-torsional plane, 78.7 +/- 4.4 degrees from abduction axis in horizontal-torsional plane, and 76.3 +/- 4.3 degrees from abduction axis in horizontal-vertical plane (+/-SD, n = 50). Time constants of slow phases were less than 0.1 second. CONCLUSIONS: Quantitative three-dimensional analysis of SOM directly confirmed that the fast phases of SOM attacks were induced by the sole contraction of the superior oblique muscle.
To investigate a resetting mechanism of torsional eye position errors, spontaneous scanning eye movements and visually guided eye movements in different lighting conditions were recorded three dimensionally. Two monkeys (Macaca fuscata, TS, MI) were engaged in this experiment. A dual scleral search coil method was used for three-dimensional (3-D) eye movement recordings. In complete darkness, the thickness of Listing's plane at the onset of spontaneous saccades (0.51/0.37 degrees (TS/MI)) and that at the end of spontaneous fixation periods (0.47/0.34 degrees (TS/MI)) were significantly (P<0.001) smaller than that at the end of spontaneous saccades (0.59/0.45 degrees (TS/MI)) and that at the onset of spontaneous fixation periods (0.58/0.44 degrees (TS/MI)). Such differences in the thickness of Listing's plane were not observed in the light (P>0.10). Amplitude of torsional drift during post-saccadic fixation period was correlated with the amount of torsional position error at the end of saccade (P<0.001). The slope of regressed line in the dark or dim light (-0.40 to -0.50/-0.32 to -0.33 (TS/MI)) was steeper than that in the light (-0.04/-0.03 to -0.09 (TS/MI)). A resetting mechanism for torsional eye position errors during post-saccadic fixation periods is active in the dark but inactive in the light.
OBJECTIVES: Although an elemental diet has been established as the primary treatment for patients with Crohn's disease, the influence of dietary fat on the elemental diet remains unclear. We have designed the first randomized, controlled trial for elemental diets containing different fat percentages in patients with active Crohn's disease. METHODS: Each patient was randomized to receive one of three dose levels of fat in an elemental diet (Elental) for 4 weeks: 10 patients received low fat (3.06 g/day), 10 patients received medium fat (16.56 g/day) and eight patients received high fat (30.06 g/day). The additional fat was composed of long-chain fatty acids. All patients were evaluated using the International Organization of Inflammatory Bowel Disease rating, plus C-reactive protein level and erythrocyte sedimentation rate, which were measured at weekly intervals. RESULTS: Although the International Organization of Inflammatory Bowel Disease rating, C-reactive protein level and erythrocyte sedimentation rate in the low-fat group decreased, the values in the medium- and high-fat groups fluctuated during the study. The remission rate after 4 weeks in each group was 80%, 40% and 25% for patients in the low-, medium- and high-fat groups, respectively. CONCLUSIONS: When the fat consisted of long-chain triglycerides, a high amount of this fat in the elemental diet formula decreased its therapeutic effect against active Crohn's disease.
The effect of intracellular charged amino acids on freeze tolerance in dough was determined by constructing homozygous diploid arginase-deficient mutants of commercial baker's yeast. An arginase mutant accumulated higher levels of arginine and/or glutamate and showed increased leavening ability during the frozen-dough baking process, suggesting that disruption of the CAR1 gene enhances freeze tolerance.
Shiga toxins (Stx) are some of the major virulence factors of enterohemorrhagic Escherichia coli strains such as serotype O157:H7. To explore how Stx might initially gain access to the bloodstream from sites of infection, frozen sections of mouse colon were immunohistochemically examined for binding sites for recombinant binding subunits (Stx1B). Binding sites were selectively expressed on the epithelium in the distal half of the mouse colon, whereas the proximal half did not exhibit any binding sites. In agreement with this observation, we also demonstrated the distal-part-restricted distribution of glycolipids that bind to Stx1B in the mouse colon. For comparison, the binding sites of several control lectins were also examined. Selective binding to the distal part of the colon was not seen with any other control lectins, including Griffonia simplicifolia lectin-I isolectin B4 (GS-I-B4), which shares alpha-galactose specificity with Stx1B. Partial overlapping of the specificities of Stx1B and GS-I-B4 was seen by assay with globotriose-conjugated multivalent ligands. The results indicate that Stx1B is stricter in the recognition of carbohydrate determinants than GS-I-B4 when examined with biological ligands.
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PURPOSE: To evaluate the clinical features of nosocomial epidemic keratoconjunctivitis(EKC) occurring in the ophthalmology ward of Sapporo Medical University Hospital and to devise preventive measures for it. MATERIALS AND METHODS: We studied the symptoms and clinical course of 2 patients who had EKC and 16 patients who had EKC caused by nosocomial infections in our hospital. We attempted to detect adenovirus antigen and viral DNA from conjunctival swabs and also to isolate the virus. RESULTS: The clinical symptoms of EKC were conjunctival hyperemia in 18 patients(100%), conjunctival follicles in 11 patients (61.1%), discharge in 8 patients(44.4%), superficial punctate keratopathy in 7 patients(38.9%), swelling of the eyelids in 3 patients(16.7%), and fever in 3 patients(16.7%). 72% were positive for Adeno-check. Adenovirus type 4 was isolated from the conjunctival swabs. We considered that the route of hospital infection was infection from the doctor's hands, from eye drops, and from contact lenses. We disclosed that nosocomical EKC had occurred in our hospital. The hospital infection was eliminated by closing the ophthalmology ward and sterilizing instruments and washing hands. CONCLUSIONS: The delay of proper measures increased the risk of nosocomical infection. We recognized the importance of careful observation of patients and immediate preventive efforts in nosocomical infection.
Basic calcium phosphate (BCP) deposition disease is a crystal-induced inflammation syndrome. We report a beneficial effect of high-dose etidronate, one of the bisphosphonates, on periarticular calcinosis in a case of arterial and periarticular BCP crystal deposition disease. A 55-year-old woman was referred to St. Marianna University Hospital because of a 30-year history of recurrent acute periarthritis. The X-ray photographs revealed periarticular calcinosis of the hand and foot, wrist, and knee joints without bony erosions and the calcification of carotid and popliteal arteries. The biopsied specimen from periarticular tissue showed Alizalin-red and von Kossa staining-positive crystals. With the diagnosis of BCP crystal-induced periarthritis, she has been treated with colchicine and probenecid. This regimen was partially effective in terms of a decrease in the frequency of periarthritic attack. Despite the treatment, periarticular calcinosis increased in size and number. She was treated with 800 mg of etidronate 3 months after the etidronate therapy; periarticular calcinosis was diminished although arterial calcification was unchanged. This case suggests that high-dose etidronate might be useful for heterotopic calcification associated with rheumatic diseases.
Methotrexate (MTX) plays an important role in treatment of rheumatoid arthritis (RA). It significantly reduce expected radiographic progression. Comparing with other traditional disease-modifying anti-rheumatic drugs (DMARDs), MTX slow radiographic progression during the first 2 years. Since combination with anti-tumor nectosis factor alpha (TNF-alpha) therapy has been shown to be effective for the early supression of disease activity, it could be usefull to minimize bone destruction in RA.
Highly water-soluble glycopolymers with poly(alpha-L-glutamic acid) (PGA) backbones carrying multivalent sialyl oligosaccharides units were chemoenzymatically synthesized as polymeric inhibitors of infection by human influenza viruses. p-Aminophenyl disaccharide glycosides were coupled with gamma-carboxyl groups of PGA side chains and enzymatically converted to Neu5Acalpha2-3Galbeta1-4GlcNAcbeta-, Neu5Acalpha2-6Galbeta1-4GlcNAcbeta-, Neu5Acalpha2-3Galbeta1-3GalNAcalpha-, and Neu5Acalpha2-3Galbeta1-3GalNAcbeta- units, respectively, by alpha2,3- or alpha2,6-sialytransferases. The glycopolymers synthesized were used for neutralization of human influenza A and B virus infection as assessed by measurement of the degree of cytopathic inhibitory effect in virus-infected MDCK cells. Among the glycopolymers tested, alpha2,6-sialo-PGA with a high molecular weight (260 kDa) most significantly inhibited infection by an influenza A virus, strain A/Memphis/1/71 (H3N2), which predominantly binds to alpha2-6 Neu5Ac residue. The alpha2,6-sialo-PGA also inhibited infection by an influenza B virus, B/Lee/40. The binding preference of viruses to terminal sialic acids was affected by core determinants of the sugar chain, Galbeta1-4GlcNAcbeta- or Galbeta1-3GalNAcalpha/beta- units. Inhibition of infection by viruses was remarkably enhanced by increasing the molecular weight and sialic acid content of glycopolymers.