Structure of furanocandin, a new antifungal antibiotic from Tricothecium sp.
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Biomedical subjects
Publications and source records attributed to N Chiba.
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A 26-year-old male with chronic myelocytic leukemia was admitted for unrelated allogeneic bone marrow transplantation (BMT). After BMT, he developed swelling of biateral submandibular glands accompanied with pneumonitis possibly due to cytomegalovirus (CMV). Biopsy from the left submandibular gland showed giant cells with nuclear inclusion bodies that were positive for anti-CMV-IE monoclonal antibody, there fore cytomegalic sialoadenitis was diagnosed. The administration of ganciclovir resulted in resolution of the pnumonitis and submandibular gland swelling. Although cytomegalic sialoadenitis is not a life-threating complication in BMT patients, it should be noted that biopsy is very useful for the diagnosis of systemic cytomegalovirus infection.
OBJECTIVES: To treat previously untreated adult patients infected with Helicobacter pylori with one of two regimens in an ambulatory community setting to assess the efficacy and safety of these regimens. METHODS: Sixty five adult patients with histologically confirmed H. pylori infection were randomly assigned in this open cohort study to 2 wk, low dose, twice daily treatment with omeprazole 20 mg and clarithromycin 250 mg (OC) (n = 31) or OC plus metronidazole 500 mg (OCM) (n = 34). At least 4 wk after treatment, H. pylori status was assessed by histology (four gastric biopsies, two each from antrum and body). RESULTS: Triple therapy with OCM was significantly better than dual therapy with OC in intent-to-treat (82.4 vs 58.1%, p = 0.03) and per protocol analysis (93.3 vs 62.1%, p = 0.004). Although there were frequent side effects (OC 19/31 61.3%; OCM 22/34 64.7% with at least one side effect), these were generally mild, and patients were able to complete nearly all of their medications (OC 97.2%, OCM 96.7% of pills taken). The only patient withdrawn due to medication side effects was in the OC arm. CONCLUSIONS: Triple therapy with OCM in a community setting eradicates H. pylori more effectively than dual therapy with OC. OCM is tolerated with high compliance despite frequent minor side effects and appears safe without the development of serious adverse events.
We have developed scanning near-field optical/atomic force microscopy (SNOM/AFM). The SNOM/AFM uses a bent optical fiber simultaneously as a dynamic force AFM cantilever and a SNOM probe. Resonant frequency of the optical fiber cantilever is 15-40 kHz. Optical resolution of the SNOM/AFM images shows less than 50 nm. The SNOM/AFM system contains photon counting system and polychrometer/intensified coupled charge devise (ICCD) system to observe fluorescence image and spectrograph of micro areas, respectively. Cultured cells were stained with fluorescein isothiocyanate (FITC)-labeled anti-keratin antibody or FITC-labeled phalloidin after treatment with Triton X-100. Fluorescence and topographic images were obtained in air and water. The fluorescence images showed clear images of keratin and actin filaments. The SNOM/AFM is perfect to observe biomaterials in liquid with a liquid chamber while the topographic Images showed subcellular structures which correspond to keratin and actin filaments.
This paper reports improvements of optical fiber cantilevers and the scanning near-field optical microscopy imaging of biological materials in liquid. In our scanning near-field optical/atomic-force microscope (SNOAM), the scanning of an optical fiber cantilever over the specimen was controlled by dynamic mode AFM to reduce damage to the probe and soft specimens. The typical resonant frequency of the optical fiber cantilever was 19.5 kHz, while it was 23.0 kHz in air. The Q-factor of the cantilever depended on the vibration amplitude and was typically 260-600 in air and 40-240 in water. The relationship between the vibration amplitude and the average sample-probe separation indicated that the cantilever worked in the non-contact mode in water, while it worked in the cyclic-contact mode in air. Cultured cells in aqueous solutions were visualized by the SNOAM, indicating that the SNOAM is suitable to observe soft specimens.
AIMS: To determine the influences of prostaglandin inhibition by indomethacin on 24-h intragastric acidity and plasma gastrin concentration, related to gastric mucosal injury. METHODS: A pre- and post-treatment study design was employed in 10 Helicobacter pylori negative healthy male subjects. All subjects underwent upper gastrointestinal endoscopy at least 3 days before and after 7 days dosing with indomethacin 50 mg t.d.s. Mucosal damage was scored according to the Lanza method, and biopsies were taken for H. pylori status and assay of mucosal concentrations of prostaglandin (PG)E2 and leukotriene (LT)B4. Before and on the last day of dosing, intragastric acidity was measured by continuous 24-h pH monitoring, and plasma gastrin levels determined by radioimmunoassay in blood samples collected over the same period. RESULTS: All subjects completed the study and no serious adverse events were reported. The mucosal injury score increased significantly from 0 (0-2) to 3.4 (0-8) (mean and range of values, P < 0.05) after dosing with indomethacin. No differences were observed in 24-h mean pH or meal stimulated plasma gastrin concentrations. Mucosal PGE2 and LTB4 were unchanged 8-10 h after the last indomethacin dose. CONCLUSIONS: Endogenous prostaglandins do not appear to alter intragastric acidity or gastrin secretion, in contrast to the PGE analogues, whose effects must be more pharmacological than physiological.
(1-->3)-beta-D-Glucans exhibit a variety of biological and immunopharmacological activities, and the significance of these activities is dependent on the structure of the glucans such as molecular weight, degree of branching, and conformation. Based on the generally accepted evidence that the conformation of clinically used Sonifilan (SPG) is a triple helix, we prepared alkaline treated SPG (SPG-OH) as a single helix conformer. In this report, we examined (A) the antitumor effect on a solid form tumor in vivo, (B) hematopoietic response on cyclophosphamide induced leukopenia, (C) antagonistic effect for zymosan mediated-hydrogen peroxide synthesis on peritoneal macrophage (PM), (D) priming effect of lipopolysaccharide (LPS) triggered tumor necrosis factor (TNF) synthesis, (E) nitric oxide synthesis of PM in vivo, and (F) hydrogen peroxide synthesis of PM in vivo. Both SPG and SPG-OH showed a significant effect on (A) and (B). The activity on (C) was stronger in SPG than SPG-OH. The activities of (D), (E), and (F) were stronger in SPG-OH. These facts strongly suggested that the glucan-mediated immunopharmacological activities were dependent on the helical conformation, and the conformation dependency varied dependent on the assays used.
Small molecular weight (MW) glucan derivatives could be a useful tool for studying the mechanisms of beta-glucan mediated biological activity, especially as antagonists for a beta-glucan receptor. This paper described the stability of various (1-->6) branched (1-->3)-beta-D-glucans to formolysis in the preparation of small MW derivatives. The glucans used were curdlan (linear), pachyman (few branches), GRN (one branch in every third main chain unit; 2/6), SPG (2/6), SSG (3/6), and OL-2 (4/6). Curdlan and pachyman were easily degraded to oligosaccharides by degradation for 20 min at 100 degrees C by 90% formic acid. However, branched glucans, especially the highly branched glucans, SSG and OL-2, were significantly resistant to degradation, and the majority remained high MW. SSG required a longer period and/or a higher temperature (121 degrees C treatment) to produce small MW derivatives. Branched glucans were also resistant to zymolyase (an endo-(1-->3)-beta-D-glucan hydrolase) digestion. These facts suggest that the (1-->6)-beta-D-branched residues contribute to the glucans' resistance to formic acid degradation and zymolyase digestion.
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We have demonstrated the nested-polymerase chain reaction (nested-PCR) assay detected from 14 mycobacterial species. We have further demonstrated the species specific restriction sites within amplified dnaJ gene, which allowed us to differentiate the mycobacterial DNA by combination of the PCR with the restriction fragment length polymorphism (PCR-RFLP). Nested-PCR-RFLP was used to detect and identified mycobacterial DNA in the sputa samples and HIV related samples. The target DNA was a 196-base pair segment of dnaJ gene. Of 68 sputum samples tested, 7 were smear positive for acid-fast bacilli and culture. The 7 samples were also identified with Mycobacterium tuberculosis by PCR-RFLP. We tested 69 HIV related samples (19 frozen samples, 22 paraffin embedded samples and 28 lymphocyte from HIV infected people). Of 38 samples were positive for nested-PCR, 8 M. tuberculosis complex, 7 M. avium, 8 M. intracellulare, and 16 others were detected by PCR-RFLP. The PCR method is useful for the rapid diagnosis of mycobacterial infection.
We described a case of adult T cell leukemia (ATL) not associated with human T-cell leukemia virus type I (HTLV-I), a clinical entity that was first reported by Shimoyama et al. A 79-year-old male was admitted with anorexia and fever in October, 1989. Physical examination revealed marked hepatosplenomegaly and superficial lymphadenopathies. Hematological examination revealed marked leukocytosis (136,300/microliters) with abnormal lymphoid cells showing highly lobulated nuclei. Hypercalcemia (11.2 mg/dl) and elevation of lactic dehydrogenase were also recognized. Surface marker analysis showed that the abnormal lymphoid cells in the peripheral blood were positive for CD2 and CD4 but negative for CD8. Southern blot analysis of the DNA from peripheral blood leukemic cells revealed monoclonal rearrangement of T-cell receptor beta-chain gene. The clinical and hematological findings of the patient were compatible with those of acute type ATL, however, serum anti-HTLV-I antibody was negative and HTLV-I proviral DNA was not detected in the leukemic cells by Southern blot analysis. Furthermore, the polymerase chain reaction showed no integration of the HTLV-I proviral DNA in the leukemic cells.
A 42-year-old woman was admitted to our hospital because of anterior chest discomfort on exercise. She had already been diagnosed as having a complete form of Behçet's disease. On auscultation, there was a grade 2/6 diastolic regurgitant murmur along the left sternal border. Echocardiogram and pulse doppler led to the diagnosis of aortic regurgitation and mitral fluttering in diastole. Left ventriculography disclosed an enlarged left ventricular chamber, but the ejection fraction was 60% within the normal range. Aortography confirmed the diagnosis of aortic regurgitation (III.) and dilatation of the ascending aorta. The coronary arteriogram was normal. An endomyocardial biopsy of the right ventricular wall revealed mild hypertrophy of the myocardial fibers and interstitial edema. In this report, we discussed a case of Behçet's disease with reference to 28 cases reported in the medical literature in Japan.
Polymerase Chain Reaction (PCR) was used to detect and to identify Mycobacterium species. In this study, 13 out of 14 Mycobacterium species were detected by using six pairs of oligonucleotide primers. The PCR product was detected by non-isotopic southern blot hybridization even when as little as 10 fg of purified M. tuberculosis DNA was used. And 8 mycobacterial species were identified by PCR-Restriction Fragment Length Polymorphism (RFLP) using two kinds of endonuclease.
Despite numerous Helicobacter pylori treatment studies, the optimum regimen(s) for its eradication remain unclear. Our objective was to determine systematically which regimen(s) gave the best pooled eradication rates, by using meta-analysis methodology. A total of 27 studies were identified. Pooled eradication rates for single (18.6%), double (48.2%), and triple therapy (82.3%) were statistically highly different (p < 0.0005). Eradication rates with amoxicillin (23.0%) and bismuth compounds (19.6%) were equivalent. Combined treatment with bismuth+metronidazole was better than bismuth+amoxicillin (55.1% vs. 43.7%, p = 0.049). Triple therapy with bismuth+metronidazole+tetracycline gave a statistically higher eradication rate (94.1%) than bismuth+metronidazole+amoxicillin (73.1%, p < 0.0005). Despite increased side effects with multiple antibiotic regimens, patients tolerated these well, without significant drop-out. The combination of bismuth, metronidazole, and tetracycline gives the best eradication rate, but the optimal doses and duration of treatment have yet to be determined. Further studies are necessary to explore factors such as antibiotic resistance and drug compliance as important factors affecting antibiotic efficacy.
A 65-year-old man, who had been treated for multiple myeloma (MM) since 1986, was admitted because of loss of consciousness in September 1989. An electrocardiogram taken just before admission showed a sinus arrest, junctional escaped rhythm, and marked bradycardia. The diagnosis of sick sinus syndrome (SSS) was made. Soon a temporary pacemaker was inserted, and the dyspnea ameliorated. However on the second day in the hospital, he had a high fever and Staphylococcus aureus was detected in the cultured blood. A diagnosis of septicemia was made, and the pacemaker was removed. He was then treated with beta-stimulants, but died in November 1989. Necropsy revealed cardiomegaly and microscopic examination showed amyloid deposits in the sinoatrial node, and the walls of the ventricles and coronary arteries. Although amyloidosis is often a complication of MM and the heart is frequently affected, SSS caused by amyloidosis associated with MM is quite unusual. In such patients, the use of a pacemaker is controversial, because amyloid deposits are occasionally accelerated by insertion of a pacemaker and for patients with hematological disorders, septicemia associated with pacemaker insertion may prove fatal.
A 62-year-old man was admitted to our hospital because of general malaise. The chest X-ray film showed severe cardiomegaly (CTR = 81%). The electrocardiogram demonstrated absence of P wave in 12-leads and regular junctional rhythm with incomplete right bundle branch block. Echocardiogram and color Doppler led to the diagnosis of mitral stenosis and regurgitation, tricuspid regurgitation with enlarged left and right atrium. Cardiac catheterization study revealed elevation of the pulmonary artery wedge pressure and the right atrial pressure without A wave. In the electrophysiologic study, no atrial electrical activity was recorded in the right atrium and the coronary sinus. However, when atrial pacing was attempted at multiple sites with stimulum strength of 10 V, there was no atrial activity at various sites. We considered that the atrial overload due to combined valvular disease for seventeen years had resulted in total and persistent atrial standstill. In this report, we discussed atrial standstill in 67 cases recorded in the medical literatures in our country.
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