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Biomedical subjects

S Yoshizawa

Publications and source records attributed to S Yoshizawa.

At least 19 recordsLinked to original sources

Structural origins of gentamicin antibiotic action.

Aminoglycoside antibiotics that bind to the ribosomal A site cause misreading of the genetic code and inhibit translocation. The clinically important aminoglycoside, gentamicin C, is a mixture of three components. Binding of each gentamicin component to the ribosome and to a model RNA oligonucleotide was studied biochemically and the structure of the RNA complexed to gentamicin C1a was solved using magnetic resonance nuclear spectroscopy. Gentamicin C1a binds in the major groove of the RNA. Rings I and II of gentamicin direct specific RNA-drug interactions. Ring III of gentamicin, which distinguishes this subclass of aminoglycosides, also directs specific RNA interactions with conserved base pairs. The structure leads to a general model for specific ribosome recognition by aminoglycoside antibiotics and a possible mechanism for translational inhibition and miscoding. This study provides a structural rationale for chemical synthesis of novel aminoglycosides.

Anti-Bacterial Agents

Temporal structure of implicit motor imagery in visual hand-shape discrimination as revealed by MEG.

We investigated the spatio-temporal brain activity on the time scale of several milliseconds related to the mental rotation task requiring judgements of hand orientation, using a whole-cortex MEG (magnetoencephalography) system. Neuronal activity in the visual cortex was observed approximately 100-200 ms from stimulus onset, and that in inferior parietal lobe followed (after 200 ms). Both of these activities showed a contralateral dominance to visual stimulus hemifield. Premotor activity started later than the inferior parietal lobe activity, and these activities partially overlapped. Activity in primary motor and/or motosensory areas was observed in some subjects. The whole-cortex neuromagnetic measurements provided the time course of activity in the human brain associated with the implicit motor imagery: visual cortex-->inferior parietal lobe<-->premotor cortex. This process is considered to be the transformation process of retinotopic locations into a body-centered reference frame necessary for the mental rotation task.

Adult

Paromomycin binding induces a local conformational change in the A-site of 16 S rRNA.

Aminoglycoside antibiotics that bind to ribosomal RNA in the aminoacyl-tRNA site (A-site) cause misreading of the genetic code and inhibit translocation. An A-site RNA oligonucleotide specifically binds to aminoglycoside antibiotics and the structure of the RNA-paromomycin complex was previously determined by nuclear magnetic resonance (NMR) spectroscopy. Here, the A-site RNA structure in its free form has been determined using heteronuclear NMR and compared to the structure of the paromomycin-RNA complex. As in the complex with paromomycin, the asymmetric internal loop is closed by a Watson-Crick base-pair (C1407.G1494) and by two non-canonical base-pairs (U1406.U1495, A1408.A1493). A1492 stacks below A1493 and is intercalated between the upper and lower stems. The comparison of the free and bound conformations of the RNA shows that two universally conserved residues of the A site of 16 S rRNA, A1492 and A1493, are displaced towards the minor groove of the RNA helix in presence of antibiotic. These changes in the RNA conformation place the N1 positions of A1492 and A1493 on the minor groove side of the A-site RNA and suggest a mechanism of action of aminoglycosides on translation.

Anti-Bacterial Agents

Hemophagocytic syndrome associated with fulminant ulcerative colitis and presumed acute pancreatitis.

We herein report a case of hemophagocytic syndrome that developed in a 25-yr-old man with fulminant ulcerative colitis and presumed acute pancreatitis. Physical examination on admission showed a chronically ill, delirious patient with an upper abdominal mass. Peripheral blood showed progressive pancytopenia and bone marrow aspirate smears revealed hypocellular bone marrow with an increase of histiocytes showing prominent hemophagocytosis. Plain abdominal radiography revealed toxic megacolon. Both ultrasound and computed tomography showed the enlargement of the pancreas, thus indicating presumed acute pancreatitis. No apparent neoplasms or viral or bacterial infections, which are normally reported to be the cause of hemophagocytic syndrome, were detected. The patient was successfully treated with high doses of prednisolone and gamma-globulin.

Acute Disease

[Interstitial cystitis in case of primary Sjögren's syndrome].

A 53-year-old woman who had xerostomia for ten years was admitted to our hospital because of refractory lower abdominal pain and pollakisuria of five years duration. Although she had undergone surgical treatments including cholecystectomy, ovarian cystectomy and groin hemiorrhaphy, she still suffered from abdominal symptoms. A diagnosis of interstitial cystitis was confirmed by hydraulic distention during a cystoscopic examination and by histopathological examination of the bladder. Her symptoms disappeared soon after the cystoscopic procedure, which also had a therapeutic effect of interstitial cystitis. Laboratory findings revealed hypergammaglobulinemia, a high titer of rheumatoid factor, positive anti-nuclear antibody, and positive anti-SS-A/Ro antibody. She was diagnosed as having primary Sjögren's syndrome based on the results of a gum test (8.5 ml/ 10 min), sialography (Stage II), and a positive minor salivary gland biopsy. Starting one month after the hydraulic distention, her abdominal symptoms gradually reappeared along with elevation of her serum IgG level. These features were markedly improved with 30 mg/day of oral prednisolone, which was then successfully tapered. These results suggested that interstitial cystitis in this case was caused by immunological abnormalities associated with Sjögren's syndrome.

Cystitis, Interstitial

[Pneumatosis cystoides intestinalis associated with intravenous pulse cyclophosphamide treatment for systemic lupus erythematosus].

Pneumatosis cystoides intestinalis (PCI) is an uncommon disease manifestation characterized by the presence of air in the bowel wall. PCI is sometimes observed in patients with progressive systemic sclerosis or mixed connective tissue disease but extremely rare in patients with systemic lupus erythematosus (SLE). We here report a patient with SLE who developed PCI after the treatment with intravenous cyclophosphamide (IVCY). This is the first case that association between IVCY and PCI was suggested. A 51-year-old woman with a 24-year history of SLE was admitted to our hospital because of skin ulcers in the lower legs. She had been receiving prednisolone orally. Laboratory findings on the present admission showed a elevated titer of anti-double stranded DNA antibody and positive LE test. She was successfully treated with three pulses of methylprednisolone followed by two IVCY together with vasodilators for her disease activity of SLE including skin manifestation. Just after the second IVCY, abdominal distention was gradually developed without any other abdominal symptoms, including abdominal pain. Abdominal radiography and computed tomography revealed pneumoperitoneum and multiple intramural air collections which involved the ascending colon primarily. Gastrointestinal series, however, showed no evidence of intestinal perforation. The diagnosis of PCI was made radiologically. After she was treated with a combined therapy with intravenous hyperalimentation and breathing with high concentration of oxygen for three weeks, PCI and pneumoperitoneum disappeared. It would be necessary that IVCY is carefully administrated, especially for the patients under the risk of PCI, such as collagen diseases.

Cyclophosphamide

3-Phosphohistidine cannot replace phosphotyrosine in high-affinity binding to phosphotyrosine binding or Src homology 2 domains.

Posttranslational phosphorylation of proteins is an important event in many cellular processes. Phosphorylated tyrosine residues can serve as association sites for other proteins in signal transduction cascades of tyrosine kinase receptors. Formation of phosphohistidine residues in proteins has been found in eukaryotic and prokaryotic organisms. Furthermore, it has been suggested that phosphohistidine might substitute for phosphotyrosine in conferring high-affinity binding to proteins involved in signal transduction. We have analyzed the ability of 3-phosphohistidine to associate with the known phosphotyrosine-specific phosphotyrosine binding and src homology 2 protein domains. From our binding studies using synthetic peptides, we conclude that 3-phosphohistidine cannot replace phosphotyrosine in conferring high-affinity binding to the phosphotyrosine binding domain of shc or the src homology 2 domain of phospholipase C-gamma1.

Amino Acid Sequence

Human cortico-hippocampal activity related to auditory discrimination revealed by neuromagnetic field.

We carried out multi-dipole estimation and pursued spatio-temporal brain activity on a time scale of several milliseconds during an auditory discrimination task using a whole-cortex type SQUID system. Neuronal activities were estimated in the medial (hippocampus, parahippocampal gyrus, etc.) and lateral temporal cortices (superior and middle temporal gyri, etc.), the dorsolateral prefrontal cortex (middle and inferior frontal gyri, etc.) and the parietal cortex (supramarginal gyrus, etc.) in the 280-400 ms latency range. The activity in the posterior hippocampal region was the most prominent and long-lasting in parallel with the activities in the other regions. Therefore, the posterior hippocampal region is a central structure engaged in auditory discrimination. The whole-cortex neuromagnetic measurements provided the possibility of imaging the time-varying activities of the human cortico-hippocampal neural networks.

Adult

GNA trinucleotide loop sequences producing extraordinarily stable DNA minihairpins.

d(GCGAAAGC) and d(GCGAAGC) fragments form extraordinarily stable DNA minihairpins containing only two G-C base pairs and a GAAA or GAA loop, respectively, with a Tm of 76 degrees C. These sequences are frequently found in some important regions such as replication origins and promoter regions for transcription. We examined all 64 possible DNA fragments, d(GCNNNGC), in which the triloop region of the d(GCGAAGC) minihairpin was randomized and found that only four fragments, d(GCGNAGC) (N = A, G, C, or T), formed extraordinarily stable minihairpins as shown by their gel mobility and resistance to a single-stranded DNA-specific exonuclease. Structural and thermodynamic analyses suggest that the extraordinary stability is caused by a unique structural property of the trinucleotide sequences corresponding to the GNA loop.

DNA

Angina pectoris occurring during granulocyte colony-stimulating factor-combined preparatory regimen for autologous peripheral blood stem cell transplantation in a patient with acute myelogenous leukaemia.

We describe a patient with acute myelogenous leukaemia who developed angina pectoris during pretransplant conditioning for autologous peripheral blood stem cell transplantation (PBSCT); the conditioning regimen consisted of cytotoxic drugs in combination with granulocyte colony-stimulating factor (G-CSF). Neutrophilia and hypercoagulability were observed at the time of angina pectoris. Recurrence of angina pectoris was not seen after nitrate and aspirin therapy. Exercise stress testing performed after PBSCT suggested the presence of myocardial ischaemia. Therefore cases at risk of vascular events should be carefully managed with prophylactic treatment during G-CSF administration.

Angina Pectoris

[Severe left ventricular dysfunction in a patient with primary Sjögren's syndrome].

A 43-year-old woman was admitted to our hospital for evaluation of shortness of breath and palpitation on exertion. She had a 20-year history of dry mouth and a 10-year history of recurrent pneumonia. She had been diagnosed as having primary Sjögren's syndrome with interstitial pneumonia at 42 years of age. On admission, cardiac ultrasonography revealed reduced left ventricular systolic function. Complications that would elicit cardiac manifestations such as viral myocarditis, amyloidosis, sarcoidosis, and ischemic heart disease, were excluded. Oral corticosteroid therapy was effective for alleviating symptoms. In this patient, it appears that primary Sjögren's syndrome is involved in the reduced left ventricular systolic function.

Adult

Remitting seronegative symmetrical synovitis with pitting edema associated with gastric carcinoma.

We report a case of remitting seronegative symmetrical synovitis with pitting edema (RS3PE syndrome) associated with gastric carcinoma in an 80-year-old woman who developed polyarthritis with marked pitting edema of the dorsa of both hands and feet 7 days after fiberscopic examination of the stomach. A mass lesion was identified and histology of the biopsy specimen revealed gastric carcinoma. Polyarthritis and edema were partially relieved by an intraarticular injection of corticosteroid. Shortly after resection of the gastric carcinoma, her symptoms and signs disappeared. She has been free of symptoms for 3 yrs without medication.

Adenocarcinoma

[(-)-Epigallocatechin gallate, the main constituent of Japanese green tea, inhibits tumor promotion of okadaic acid].

(-)-Epigallocatechin gallate (EGCG), the main constituent of green tea, inhibited a tumor promoting activity of okadaic acid in a two-stage carcinogenesis experiment on mouse skin. The group treated with a single application of 100 micrograms 7, 12-dimethylbenz (a) anthracene followed by repeated applications of 1 microgram okadaic acid resulted in 80% of tumor-bearing mice and 4.7 of average numbers of tumors per mouse in week 20. Repeated applications of 5 mg EGCG, prior to okadaic acid, completely inhibited the tumor formation in mice up to week 20. The inhibitory effects of EGCG with two different doses of each application, 1 mg and 5 mg, were dose-dependent. A topical application of 5 mg EGCG immediately reduced the specific binding of [3H]okadaic acid to a particulate fraction of mouse skin to as low as 30% of control. According to the Scatchard analysis, the reduction of specific [3H]okadaic acid binding was mainly due to the reduction of the binding sites, not due to the change of the affinity. The reduction of the specific binding was closely related to the inhibitory effct of EGCG on tumor promotion of okadaic acid. Since EGCG is a non-toxic compound, ingested in green tea in daily life in Japan, EGCG is one of the candidates for practical cancer chemopreventive agents.

Animals

Urinary C4 excretion in systemic lupus erythematosus.

The fourth component of complement (C4) in urine was measured in 19 patients with systemic lupus erythematosus (SLE). Urinary C4 was detectable in all SLE patients using an enzyme linked immunosorbent assay. In 11 of 13 patients whose urinary C4 was serially measured, a decrease of urinary C4 was found in parallel with a decrease of disease activity of SLE. In the remaining 2 patients, the amount of C4 increased preceding a flare-up of the disease. The measurement of urinary C4 may be useful in evaluating the disease activity of SLE in individual patients and sometimes in predicting the flare-up of the disease. The specific hemolytic activity of excreted C4 and Western blotting analysis showed that urinary C4 consisted mainly of degraded fragments of C4. In two cases, camostat, a serine protease inhibitor, rapidly decreased the urinary C4 excretion, suggesting that the complement activation occurred in the glomerulus in lupus nephritis.

Adolescent

Isolation of influenza A and B viruses in HeLa cells.

The HeLa cell line which is one of the most popular cell lines was shown to be suitable for isolation of types A (H3N2) and B influenza viruses from throat washings of patients. Sixty-nine and 67 out of 147 throat washings taken from patients during the period from January to April 1994, were positive for influenza A virus in HeLa cells and MDCK cells respectively. Seven out of 10 throat washings taken between January and March, 1993, were positive for influenza B virus in MDCK. Of these 7, 4 were also positive for HeLa cells.

Animals