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Biomedical subjects

A Hashimoto

Publications and source records attributed to A Hashimoto.

At least 73 records · Page 4Linked to original sources

[Recent knowledge allowing diagnosis and treatment of deep-seated trichosporonosis].

Deep-seated trichosporonosis is a lethal opportunistic infection in immunocompromised patients. For the rapid diagnosis of this condition, we developed a novel nested-PCR assay that detects DNA specific for clinically important strains of Trichosporon in serum of patients with disseminated trichosporonosis. In this assay, two sets of oligonucleotide primers were derived from the sequence of 26 S ribosomal RNA genes of T. asahii. The specific fragment was amplified from T. asahii and T. mucoides but not from other microorganisms. In a retrospective study using serum samples of patients with disseminated trichosporonosis, the specific fragment was detected in 64% (7 of 11). To treat this infection, we studied the efficacy of rhG-CSF alone and in combination with antifungal agents against disseminated trichosporonosis in neutropenic mice. The results suggested that rhG-CSF might be a useful immunomodulator against Trichosporon infections and the therapeutic outcome might be better when used in combination with antifungal agents.

Adjuvants, Immunologic↗

Enhancement of fibrinolytic activity of vascular endothelial cells by chaetoglobosin A, crinipellin B, geodin and triticone B.

Four fungal metabolites, chaetoglobosin A (CGA), crinipellin B (CPB), geodin (GE) and triticone B (TTB), were found to enhance fibrinolytic activity of bovine aortic endothelial cells. Plasmin generation on the cells was elevated 2- to 4-fold when treated with these agents at a concentration of 3 approximately 100 microM. These effects were dependent on plasminogen and inhibited by anti-urokinase antibody. The effect of CGA, but not of CPB, GE and TTB, was abolished by cycloheximide. In a cell-free system, plasmin and urokinase activities as well as urokinase-catalyzed plasminogen activation were not enhanced by these agents. CGA, but not others, induced the production of urokinase in endothelial cells. CPB and GE accelerated plasminogen activator inhibitor- 1 (PAI-1) inactivation, and TTB caused direct, reversible inhibition of PAI-1. Thus, induction of urokinase by CGA and inhibition of PAI-1 by CPB, GE and TTB may, at least partly, account for the elevation of fibrinolytic activity of endothelial cells.

Animals↗

[Anti-angiogenic activities of UFT and its metabolites, GHB and GBL, in the dorsal air sac (DAS) model in mice].

We investigated the effects of UFT and its metabolites, GHB and GBL, on angiogenesis induced by tumor cells in a dorsal air sac (DAS) assay in mice. Five tumor cell lines (murine renal carcinoma; RENCA, human gastric cancer; 4-1ST, human small-cell lung carcinoma; LX-1, and human colon carcinoma; DLD-1, KM-20C) were used in the DAS assay. In this model, UFT demonstrated a significant anti-angiogenic activity in a dose-dependent manner while 5-FU (19 mg/kg/day) and 5'-DFUR (200 mg/kg/day) were less effective. Moreover, tegafur (FT), a component of UFT, and gamma-hydroxybutyric acid (GHB) and gamma-butyrolactone (GBL), in vivo metabolites of UFT, inhibited angiogenesis induced by RENCA cells. The inhibitory effects of 5-FU, GHB, and GBL on angiogenesis were increased with administration by continuous infusion, providing a suitable pharmacokinetic profile. These results suggest that GHB and GBL are involved in the expression of anti-angiogenic activity of UFT.

4-Butyrolactone↗

[Early and late results of combined valvular and coronary artery operations].

A total of 122 patients with ischemic heart disease underwent valvular surgery. Thirty-nine had combined CABG and aortic valve surgery (included Bentall method), 72 had CABG and mitral valve operations, and 8 patients had CABG and double or triple valve operations. Only 3 patients for ruptured papillary muscle due to acute myocardial infarction had isolated mitral valve replacement. Early mortality was 5.1% AV, 2.8% MV and 12.5% DTV in the combined groups and 0% in the valve only group. The grafts patency rate was 93.5%. Univariate analysis of risk factors selected in the dialysis patients and the patients age older than 65 years as the strongest predictors for early death. At the mean follow up period of 5.4 +/- 4.8 year after surgery, the 5-year all death free rates were 57.9 +/- 9.6% AV, 69.6 +/- 5.8% MV and 75.0 +/- 15.3% DTV. The 5-year cardiac death free rates were 73.8 +/- 9.0% AV, 77.5 +/- 5.4% MD and 75.0 +/- 15.3% DTV.

Adolescent↗

A multiple alignment algorithm for metabolic pathway analysis using enzyme hierarchy.

In many of the chemical reactions in living cells, enzymes act as catalysts in the conversion of certain compounds (substrates) into other compounds (products). Comparative analyses of the metabolic pathways formed by such reactions give important information on their evolution and on pharmacological targets (Dandekar et al. 1999). Each of the enzymes that constitute a pathway is classified according to the EC (Enzyme Commission) numbering system, which consists of four sets of numbers that categorize the type of the chemical reaction catalyzed. In this study, we consider that reaction similarities can be expressed by the similarities between EC numbers of the respective enzymes. Therefore, in order to find a common pattern among pathways, it is desirable to be able to use the functional hierarchy of EC numbers to express the reaction similarities. In this paper, we propose a multiple alignment algorithm utilizing information content that is extended to symbols having a hierarchical structure. The effectiveness of our method is demonstrated by applying the method to pathway analyses of sugar, DNA and amino acid metabolisms.

Algorithms↗

UFT and its metabolites inhibit cancer-induced angiogenesis. Via a VEGF-related pathway.

Treatment with UFT for spontaneous lung metastasis of murine renal carcinoma (RENCA) after resection of the primary tumor has resulted in significant prolongation of the life span of tumor-bearing animals. UFT inhibited the growth of metastatic nodules in the lung, apparently via decreased density of microvessels in the metastatic foci. Subsequent experiments used dorsal air sac assay to directly trace newly forming microvessels. UFT abrogated the process of angiogenesis, induced by the RENCA cells, in a dose-dependent manner. The inhibitory effect appeared to originate from tegafur, a component of UFT, and from its known metabolites: fluorouracil (5-FU), gamma-hydroxybutyric acid (GHB), and gamma-butyrolactone (GBL). The inhibition of angiogenesis by UFT appeared to be a common phenomenon, also observed in other human cancer cell lines characterized by an excessive production of vascular endothelial growth factor (VEGF)--such as gastric, lung, and colon cancers. In vitro analysis revealed that 5-FU and gamma-hydroxybutyric acid regulated VEGF-dependent responses of human umbilical vein endothelial cells. Dorsal air sac assay revealed that UFT, 5-FU, and gamma-hydroxybutyric acid strongly inhibited the angiogenesis induced by recombinant human VEGF. These data suggest that the antiangiogenic activity of UFT is at least partially associated with an ability of the metabolites of UFT to interfere with VEGF-dependent responses of vascular endothelial cells.

Air Sacs↗

Shc regulates epidermal growth factor-induced activation of the JNK signaling pathway.

Two adaptor molecules, Grb2 and Shc, have been implicated in the extracellular signal-regulated kinase (ERK) activation by receptor tyrosine kinases such as the epidermal growth factor receptor (EGFR). Here we show that the EGF-mediated ERK activation is abolished by loss of Grb2, whereas this response is not affected by loss of Shc. Conversely, the EGF-mediated c-Jun N-terminal kinase (JNK) activation is dependent on Shc, but not Grb2. These findings strongly support distinct roles for Grb2 and Shc in controlling ERK and JNK activation after EGF stimulation.

Adaptor Proteins, Signal Transducing↗

The role of B cells in the establishment of T cell response in mice infected with an intracellular bacteria, Listeria monocytogenes.

To clarify the role of B cells in the establishment of T cell response against intracellular bacteria, B-cell-deficient (muMT-/-) mice were infected with an intracellular bacteria, Listeria monocytogenes, and T cell response against the bacteria was analyzed. On day 6 of primary Listeria infection, spleen T cells of the muMT-/- mice showed significantly lower levels of proliferative response and IFN-gamma production than those of normal infected mice after in vitro stimulation with listerial antigen. Even in the secondary Listeria infection after immunization with viable bacteria, spleen T cells of the muMT-/- mice proliferated and produced IFN-gamma against listerial antigen at significantly lower levels than those of normal immunized mice. These results demonstrate participation of B cells in priming of Listeria-specific T cells in vivo. However, B cells failed to present Listeria antigen to Listeria-specific T cells in vitro unless Listeria antigen was solubilized. Furthermore, transfer of immune serum from Listeria-infected normal mice failed to enhance the Listeria-specific T cell response of muMT-/- mice. The results indicate that B cells support the T cell response against intracellular bacteria through a mechanism other than their Ig production or antigen presentation function.

Animals↗

Inhibitory modulation of B cell receptor-mediated Ca2+ mobilization by Src homology 2 domain-containing inositol 5'-phosphatase (SHIP).

Src homology 2 domain-containing inositol 5'-phosphatase (SHIP) mediates inhibitory signals that attenuate intracellular Ca2+ mobilization in B cells upon B cell receptor (BCR) stimulation. To clarify the mechanisms affected by SHIP, we analyzed Ca2+ mobilization in the DT40 B cell line in which the SHIP gene was disrupted. In SHIP-deficient cells, Ca2+ transient elicited by BCR stimulation was more prolonged than that in control cells both in the presence and absence of extracellular Ca2+. Inositol 1,4, 5-trisphosphate production following BCR stimulation was enhanced in SHIP-deficient cells. In SHIP-deficient cells in comparison with the control cells, BCR stimulation in the absence of extracellular Ca2+ induced a greater degree of Ca2+ store depletion and the Ca2+ influx upon re-addition of extracellular Ca2+ was also greater. However, store-operated Ca2+ influx (SOC) elicited by thapsigargin-induced store depletion was not affected by SHIP. These results indicate that the primary target pathway of SHIP is the Ca2+ release from the stores, and that Ca2+ influx by the SOC mechanism is secondarily controlled by the level of Ca2+ in the stores without direct inhibition of SOC. In this way, SHIP may play an important role in ensuring the robust tuning of Ca2+ signaling in B cells.

Animals↗

16O excesses in olivine inclusions in Yamato-86009 and Murchison chondrites and their relation to CAIs.

In situ ion microprobe analyses of oxygen isotopes in Yamato-86009 and Murchison chondrites show that they contain abundant olivine-rich inclusions that have large oxygen-16 (16O) excesses, similar to those in spinel grains in calcium-aluminium-rich inclusions in Allende and other carbonaceous chondrites. The existence of 16O-enriched olivine-rich inclusions suggests that oxygen isotopic anomalies were more extensive in the early solar system than was previously thought and that their origin may be attributed to a nebular chemical process rather than to an unidentified 16O-rich carrier of presolar origin.

Aluminum↗

Management of urinary complications in Crohn's disease.

Among the 127 patients who underwent surgical treatment for Crohn's disease at Tohoku University Hospital, urinary complications were noted in 13 patients (10.2%), including urolithiasis in 6 patients (4.7%), a ureteral obstruction in 4 (3.1%), and urinary fistula in 3 (2.4%). In patients with urolithiasis, conservative therapy was effective. An ureteral obstruction was detected on the right side in all 4 of these cases because of the inflamed terminal ileum. In 2 of the 4 cases, the symptoms improved by either preoperative total parenteral nutrition or elemental diet therapy. A resection of the inflamed intestine was necessary in all cases. In patients with urinary fistulas, a resection of the inflamed intestine combined with a reconstruction of the urinary tract was carried out after total parenteral nutrition. In conclusion, conservative therapy with preoperative total parenteral nutrition or elemental diet therapy proved to be effective for a ureteral obstruction since it improved the intestinal inflammation. As a definitive treatment, surgery is still necessary for the management of urinary fistulas and ureteral obstruction. Based on our findings, patients with urolithiasis in Crohn's disease should thus be treated conservatively in the same way as patients without Crohn's disease.

Adolescent↗

Turcot syndrome with colonic obstruction and small intestinal invagination: report of a case.

We report herein the case of a 16-year-old boy diagnosed as having Turcot syndrome, otherwise known as glioma-polyposis syndrome. The patient was transferred from the Department of Neurosurgery where he was undergoing investigation of a brain tumor, to the Department of Medicine for investigation of gastrointestinal symptoms. The patient was diagnosed as having Turcot syndrome, and was then transferred to the Department of Surgery for treatment of an obstruction in the sigmoid colon and small intestinal invagination. A subtotal colectomy with side-to-end ileoproctostomy and release of the invaginations was carried out. Multiple polyps were found in the colon, two of which, including a large polyp that obstructed the colonic lumen, were confirmed histologically to be adenocarcinoma. The remaining polyps were adenomas. A biopsy of the brain tumor confirmed a diagnosis of astrocytoma (WHO grade II). This case report describes the characteristic features of Turcot syndrome presented by this patient.

Adenocarcinoma↗

Limitations of spontaneous reperfusion and conventional medical therapy to afford myocardial protection through antecedent angina pectoris in acute myocardial infarction.

Despite the cardioprotective effect of rapid coronary reperfusion, the effects of spontaneous recanalization on myocardial viability and metabolism are unknown. We studied whether preinfarction angina affords cardioprotection when spontaneous coronary reperfusion occurred in acute infarct patients. Myocardial tomographies with thallium and I-123-labeled-beta-methyl-p-iodophenyl penta-decanoic acid (BMIPP) were performed in 27 acute myocardial infarct patients treated medically: 15 patients had preexisting angina before infarction (group A) and 12 did not (group B). Thallium and BMIPP abnormalities and regional function were quantified by a polar map and contrast ventriculography, respectively. There was no significant difference between thallium and BMIPP in the severity index in groups A and B (89 +/- 97 vs. 85 +/- 68, 97 +/- 28 vs. 95 +/- 27, respectively), and no significant difference between the groups in the thallium or BMIPP severity index. The ratio of the thallium severity index to that of BMIPP and the regional wall-motion abnormality index were identical in groups A and B. Both patient groups were divided into 2 subgroups based on the presence or absence of spontaneous coronary reperfusion: subgroups A1 and A2, and subgroups B1 and B2, respectively. There were no significant differences among the 4 subgroups in severity indexes for both tracers, the thallium/BMIPP ratio, or the asynergy score. The BMIPP severity index correlated significantly with that of thallium in all subgroups, but no significant difference between the regression lines was found. It is therefore unlikely that spontaneous coronary recanalization affords beneficial effects through preservation of myocardial viability in an ischemia-related zone, suggesting that the cardioprotective effect of preinfarction angina is a limited phenomenon in patients undergoing rapid coronary reperfusion.

Adult↗

Structure of the immediate early gene of canine herpesvirus.

The nucleotide sequence of the immediate early (IE) gene of canine herpesvirus was determined. This gene was located in the inverted repeat regions, encoding a polypeptide of 1,383 amino acids. The predicted amino acid sequence was most closely related to that of the feline herpesvirus 1 IE protein among those of other alphaherpesviruses. DNA binding and transcriptional activation domains were found in the IE protein. A spliced region of the IE gene transcript was determined in its 5' non-coding region.

Amino Acid Sequence↗

Extensive aortic reconstruction for aortic aneurysms in Marfan syndrome.

BACKGROUND: Marfan syndrome patients frequently develop aneurysms or dissections involving multiple segments of the aorta, and occasionally require staged replacement of the entire aorta. This study reviews the surgical outcome of patients with Marfan syndrome who underwent extensive aortic reconstruction. Extensive reconstruction is defined as reconstruction of more than two segments of the ascending, arch, descending thoracic, or abdominal aorta. METHODS: From March 1973 to December 1997, 101 patients with Marfan syndrome underwent aortic operation. Twenty-six patients (25.7%) had extensive aortic reconstruction. All 26 patients suffered from aortic dissection: 13 patients had Stanford type A and 13 had type B dissection. Twenty-three patients (88.4%) had annuloaortic ectasia and aortic regurgitation. Surgical procedures included composite valve graft replacement (n = 23, 88.4%), aortic arch reconstruction (n = 15, 57.7%), graft replacement of the descending thoracic aorta (n = 6, 23.1%), and graft replacement of the thoracoabdominal aorta (n = 16, 61.5%). Five patients (19.2%) had total thoracoabdominal aortic replacement, and three patients (11.5%) had replacement of the entire aorta. Twenty-one patients (80.8%) required multiple operations. RESULTS: Follow-up was complete in all patients. The 30-day survival rate was 88.5%. None of the survivors had paraplegia or paraparesis. The overall long-term survival rate was 88.5 +/- 6% at 1 year, and 81.7 +/- 9% at 9 years. CONCLUSIONS: Aortic surgery prolongs survival in patients with Marfan syndrome, and currently there is a relatively low associated morbidity and mortality even for aggressive surgical treatment.

Adult↗

Growth of pea epicotyl in low magnetic field: implication for space research.

A magnetic field is an inescapable environmental factor for plants on the earth. However, its impact on plant growth is not well understood. In order to survey how magnetic fields affect plant, Alaska pea seedlings were incubated under low magnetic field (LMF) and also in the normal geo-magnetic environment. Two-day-old etiolated seedlings were incubated in a magnetic shield box and in a control box. Sedimentation of amyloplasts was examined in the epicotyls of seedlings grown under these two conditions. The elongation of epicotyls was promoted by LMF. Elongation was most prominent in the middle part of the epicotyls. Cell elongation and increased osmotic pressure of cell sap were found in the epidermal cells exposed to LMF. When the gravitational environment was 1G, the epicotyls incubated under both LMF and normal geomagnetic field grew straight upward and amyloplasts sedimented similarly. However, under simulated microgravity (clinostat), epicotyl and cell elongation was promoted. Furthermore, the epicotyls bent and amyloplasts were dispersed in the cells in simulated microgravity. The dispersion of amyloplasts may relate to the posture control in epicotyl growth under simulated microgravity generated by 3D clinorotation, since it was not observed under LMF in 1G. Since enhanced elongation of cells was commonly seen both at LMF and in simulated microgravity, all elongation on the 3D-clinostat could result from pseudo-low magnetic field, as a by-product of clinorotation. (i.e., clinostat results could be based on randomization of magnetic field together with randomization of gravity vector.) Our results point to the possible use of space for studies in magnetic biology. With space experiments, the effects of dominant environmental factors, such as gravity on plants, could be neutralized or controlled for to reveal magnetic effects more clearly.

Cell Wall↗

Growth of Prunus tree stems under simulated microgravity conditions.

Stem growth of Prunus trees under simulated microgravity conditions was examined using a three-dimensional clinostat. The stems elongated with bending under such conditions. Stem elongation and leaf expansion were both promoted, whereas the formation of xylem in the secondary thickening growth was inhibited under the simulated microgravity condition. In secondary xylem, sedimentable amyloplasts were observed in the 1g control. The present results suggest that stem elongation and leaf expansion may be inhibited at 1g, while growth direction and secondary xylem formation depend on a gravity stimulus. A space experiment is expected to advance research on thickening growth in trees. Grant Numbers: 07456073, 1D 215.

Gravitation↗

Cardiac BMIPP imaging in acute myocardial infarction.

Fatty acid metabolism functions as a major energy-producing system under aerobic conditions, but it is impaired immediately after myocardial ischaemia. This imaging can provide intracellular information which cannot be obtained by angiographical, perfusional or functional analysis. 123I-BMIPP and perfusion imagings in patients with acute myocardial infarction have demonstrated three different correlations between myocardial perfusion and fatty acid metabolism: concordant defects of perfusion and BMIPP which represent scar or non-viable tissue; lower BMIPP uptake relative to perfusion (perfusion-BMIPP mismatch) which implicates metabolically damaged, often dysynergic, but viable myocardium; and equivalently normal uptakes of perfusion and BMIPP in completely salvaged myocardium. Identification of these perfusion-metabolism correlations contributes to the detection of ischaemia-related myocardial injury in viable and non-viable myocardium, to the prediction of post-ischaemic or post-interventional functional recovery and to the identification of patients who have myocardium at ischaemic risk. Further clinical investigations might reveal more clearly the pathophysiological and prognostic implications of cardiac BMIPP imaging in patients with acute myocardial infarction.

Fatty Acids↗