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Biomedical subjects

A Yoneyama

Publications and source records attributed to A Yoneyama.

At least 19 recordsLinked to original sources

Quantitative analysis of amyloid plaques in a mouse model of Alzheimer's disease by phase-contrast X-ray computed tomography.

Densely aggregated beta-amyloid peptides are believed to play a key role in the pathogenesis of Alzheimer's disease. Amyloid plaques are a potential target for molecular imaging to determine the clinical status of Alzheimer's disease. Phase-contrast X-ray imaging combined with computed tomography is a promising technique that can be used to visualize the physical density of structures in biological tissues non-invasively, and without the use of imaging agents. Using brain tissue isolated from a mouse model of Alzheimer's disease, we show that beta-amyloid 40-positive/beta-amyloid 42-positive amyloid plaques, but not beta-amyloid 40-negative/beta-amyloid 42-positive amyloid plaques, exist as high-density aggregates that can be specifically detected by phase-contrast X-ray computed tomography. The phase-contrast X-ray computed tomography detected beta-amyloid 40-positive/beta-amyloid 42-positive amyloid plaques in three-dimensions with an extremely high sensitivity comparable to that of histological analysis, and also enabled the load of amyloid plaques to be quantified. Furthermore, the use of phase-contrast X-ray computed tomography reveals that the physical density of beta-amyloid 40-positive/beta-amyloid 42-positive amyloid plaques increases with age, and that the large volume, high-density, amyloid plaques that are specifically observed in aged Alzheimer's disease mice are closely associated with neuritic dystrophy. These results demonstrate that phase-contrast X-ray computed tomography is a highly sensitive imaging technique for analyzing dense-cored amyloid plaques in postmortem samples, and is beneficial in elucidating amyloid pathophysiology in Alzheimer's disease.

Aging↗

Intestinal thrombotic microangiopathy following reduced-intensity umbilical cord blood transplantation.

Thrombotic microangiopathy (TMA) is a significant complication after hematopoietic stem-cell transplantation (HSCT); however, there is little information on it following reduced-intensity cord blood transplantation (RI-CBT). We reviewed the medical records of 123 adult patients who received RI-CBT at Toranomon Hospital between January 2002 and August 2004. TMA was diagnosed in seven patients based on intestinal biopsy (n = 6) or autopsy results (n = 1). While these patients showed some clinical symptoms such as diarrhea and/or abdominal pain, mental status alterations or neurological disorders were not observed in any of them. Laboratory results were mostly normal at the onset of TMA; >2% fragmented erythrocytes (n = 1), <10 mg/dl haptoglobin (n = 1), and >200 IU/dl lactic dehydrogenase (LD) (n = 4). On endoscopic examination, TMA lesions, consisting of ulcers, erosions, and diffuse exfoliation, were distributed spottily from terminal ileum to rectum. Intestinal graft-versus-host disease (GVHD) and cytomegalovirus (CMV) colitis were confirmed in five and four patients, respectively. With therapeutic measures including supportive care (n = 4), fresh frozen plasma (n = 1), and a reduction of immunosuppressive agents (n = 1), TMA improved in four patients. The present study demonstrates that intestinal TMA is a significant complication after RI-CBT. Since conventional diagnostic criteria can overlook TMA, its diagnosis requires careful examination of the gastrointestinal tract using endoscopy with biopsy.

Adolescent↗

In vitro antiseptic susceptibility of clinical isolates from nosocomial infections.

To evaluate the susceptibility of a large number of strains to various antiseptics, we elaborated a simple, qualitative broth turbidity method in which we could quickly judge the efficacy visually. For this method, we prepared a modified neutralizer broth, consisting of trypticase soy broth containing 15% Tween 80, 1% soybean lecithin and 0.5% sodium thiosulfate. The susceptibilities of Serratia marcescens No. 26 to 4 antiseptics obtained from the turbidity method showed a good agreement with those obtained from the colony-counting method; the 4 antiseptics tested were povidone-iodine (PVP-I), chlorhexidine gluconate (CHG), benzalkonium chloride (BAC) and alkyldiaminoethylglycine hydrochloride (AEG). Both PVP-I and BAC had complete efficacy in 0.5 min against all isolates tested [100 isolates of S. marcescens, 103 of Klebsiella pneumoniae, 99 of Pseudomonas aeruginosa, 19 of Alcaligenes faecalis and 30 of A. xylosoxidans subsp. xylosoxydans (A. xylosoxydans)]. In contrast, the effectiveness of CHG was weak compared with PVP-I, BAC and AEG. Strong resistance against AEG was noted even after 3-min exposure in 1 isolate each of A. faecalis and A. xylosoxydans. It is concluded that the turbidity test is a simple and accurate method to evaluate susceptibility to various antiseptics and that it is suitable for a screening of a large number of strains. Among the 4 antiseptics tested, PVP-I and BAC showed a consistently high activity against all isolates, confirming PVP-I and BAC to be clinically useful antiseptics.

Anti-Infective Agents, Local↗

Two cases of long lasting bacteremia due to Mycobacterium avium complex despite new macrolides-containing regimens in patients with acquired immunodeficiency syndrome.

The prognosis of Mycobacterium avium complex (MAC) infection has been improved by new macrolides-containing regimens and the use of highly active antiretroviral therapy (HAART) in the treatment of acquired immunodeficiency syndrome (AIDS). We report on two AIDS cases with long lasting bacteremia due to MAC under this regimen. Both patients experienced problems due to side effects from the anti-MAC regimen and from an immune-reconstitution syndrome related to HAART. MAC infection persisted despite treatment, however, no anti-MAC drug-resistant isolates emerged throughout the clinical course in either case. These cases demonstrate that therapy for disseminated MAC infection is sometimes difficult even with HAART and macrolides-containing regimens.

Acquired Immunodeficiency Syndrome↗

[Infectious mononucleosis].

Infectious mononucleosis(IM) is a primary Epstein-Barr virus (EBV)infection. Since heterophil antibody negative IM is common in Japan, EBV antibody(presence of VCA-IgM or anti-EA, high titers of VCA-IgG in the absence of anti-EBNA) is useful for serologic diagnosis of IM. Although EBV causes the continuous growth of lymphoid cell lines in vitro and causes malignant diseases such as Burkitt lymphoma, nasopharyngeal cancer and malignant lymphomas in immunocompromised patients, IM is usually self-limiting, and after primary infection EBV persists in B cells throughout life without producing symptoms. In the present study, we studied CD8+ lymphocytes of patients with IM and demonstrate an increase in lymphocytes expressing HLA-DR and CD45RO, increase of intracellular pH, elevated plasma levels of sCD8, indicating activation of the subset. We also demonstrate activation of CD4+ T lymphocytes and gamma delta T lymphocytes. Activation of these immune systems in response to EBV is supposed to play an important role in assuring the benign course of IM.

CD4 Lymphocyte Count↗

Susceptibility to vancomycin of methicillin-resistant Staphylococcus aureus isolated in a university hospital in Japan.

Intravenous vancomycin was approved in 1991 in Japan and has been widely used for treatment of infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Consequently, ever since the initial discovery of vancomycin intermediate-resistant S. aureus in Japan, the vancomycin resistance of this organism has been a great concern in clinical settings. We investigated whether vancomycin resistance had emerged in MRSA isolated in our hospital since the approval of the use of intravenous vancomycin. Vancomycin susceptibility was evaluated on the basis of minimum inhibitory concentrations determined by the agar dilution method and a heterogeneous resistance examination. The median minimum inhibitory concentration of the 69 MRSA strains isolated in 1988 and the 74 isolated in 1998 was 0.75 microgram/ml and 1.0 microgram/ml, respectively (p < 0.001), however, all of the strains were classified in the susceptible group. None of them was an MRSA heterogeneously resistant to vancomycin (hetero-VRSA), which has been defined as a strain having a 1/10(6) or greater heterogeneously resistant subpopulation to vancomycin. In another set of investigations, no hetero-VRSA were found among 12 other MRSA strains isolated after intravenous administration of vancomycin for 14 or more days (range: 14 to 77 days). We conclude that while the use of intravenous vancomycin may have slightly lowered the vancomycin susceptibility of MRSA in our hospital, the decrease in so small that it may not be significant clinically. In addition, no hetero-VRSA were found in our hospial.

Aged↗

[Hypokalemic periodic paralysis during treatment of acute promyelocytic leukemia].

A 40-year-old man was admitted with fever and purpura. He was diagnosed as having acute promyelocytic leukemia, and treated with all-trans retinoic acid. After achieving complete remission, he received consolidation therapy. During the chemotherapy, quadriplegia occurred three times. This was diagnosed as hypokalemic periodic paralysis because of the patient's low serum potassium level. Results of hormone and urine examinations showed no indication of secondary hypokalemia. However, the patient had a history of quadriplegia of unknown etiology at the age of 36. We speculated that in addition to the patient's predisposition to hypokalemic periodic paralysis, chemotherapy including prednisolone, and excessive ingestion of carbohydrate had induced his quadriplegia.

Adult↗

Effects of dehydroepiandrosterone on mitogen-activated protein kinase in human aortic smooth muscle cells.

The objective of the present study was to determine whether dehydroepiandrosterone (DHEA) modifies growth factor-induced mitogen-activated protein kinase (MAPK) activation, based on our previous study demonstrating that DHEA attenuates fetal calf serum-induced proliferation in human male aortic smooth muscle cells (human male aortic SMCs). Human male aortic SMCs were used for this study. Platelet-derived growth factor-BB (PDGF-BB), epidermal growth factor (EGF), and basic fibroblast growth factor (bFGF), but not insulin-like growth factor-1 (IGF-1), stimulated MAPK activity. Only MAPK activation induced by PDGF-BB was reduced by pretreatment with DHEA, although DHEA did not affect the MAPK activation induced by EGF or bFGF. The basal and PDGF-stimulated MAPK activity were decreased by two types of cyclic AMP (cAMP) elevating agents and increased by cAMP-dependent protein kinase (PKA) inhibitor in human male aortic SMCs, suggesting that cAMP regulates MAPK negatively. The intracellular cAMP was increased by PDGF-BB. The increase of cAMP by PDGF-BB was augmented by pretreatment with DHEA, although DHEA alone did not affect cAMP. Neither EGF nor bFGF affected cAMP with and without DHEA pretreatment. Secretion of PGE2 induced by PDGF was augmented by pretreatment with DHEA. Stimulatory effects of DHEA on the production of PGE2 and cAMP were partially canceled by aromatase inhibitor and completely canceled by indomethacin or selective inhibitor of cyclooxygenase-2. These results suggest that DHEA inhibited MAPK activation induced by PDGF-BB via PGE2 overproduction and subsequent cAMP-dependent pathway in human male aortic SMCs.

8-Bromo Cyclic Adenosine Monophosphate↗

Takayasu's arteritis accompanied with massive pericardial effusion--a case report.

A 40-year-old woman who had been treated for Takayasu's arteritis was admitted to the hospital with fever, fatigue, malaise, and severe chest pain. Computed tomography of the chest demonstrated massive pericardial effusion and bilateral pleural effusion. In laboratory data, the C-reactive protein was high at 22.0 mg/dL, and erythrocyte sedimentation rate was also high at 80 mm/hr. The diagnosis was pericarditis with a recurrence of the systemic inflammatory process of Takayasu's arteritis. The patient was treated with methylprednisolone pulse therapy. Her massive pericardial effusion disappeared without pericardiocentesis.

Adult↗

[Comparison of the newly developed MB redox system with mycobacteria growth indicator tube (MGIT) and 2% Ogawa egg media for recovery of mycobacteria in clinical specimens].

The rate of recovery and the mean time to detection of mycobacteria in clinical specimens were determined in a newly-developed MB Redox system based on liquid medium, and the results were compared with those of MGIT and 2% Ogawa egg media. From 587 sputum specimens processed, totally 203 mycobacterial isolates were detected, of which 177 (87.2%) with MB Redox, 185 (91.1%) with MGIT and 133 (65.6%) with 2% Ogawa medium. The difference in the percentages of positive cultures between either of the two liquid media and 2% Ogawa medium was significant (p < 0.0001). The mean time to detection of the Mycobacterium tuberculosis complex was 17.5 days with MB Redox, 18.7 days with MGIT, and 26.2 days with 2% Ogawa medium. The contamination rates were 1.5, 1.7, and 4.1% for MB Redox, MGIT, and 2% Ogawa medium, respectively. In conclusion, both MB Redox and MGIT systems, based on liquid medium, are more efficient than 2% Ogawa medium for the recovery of mycobacteria in clinical specimens.

Bacteriological Techniques↗

Phase-Contrast Tomographic Imaging Using an X-ray Interferometer.

Apparatus for phase-contrast X-ray computed tomography using a monolithic X-ray interferometer is presented with some observational results for human breast tissues. Structures characteristic of the tissues were revealed in the phase-contrast tomograms. The procedure of image analysis consists of phase retrieval from X-ray interference patterns and tomographic image reconstruction from the retrieved phase shift. Next, feasibility of phase-contrast imaging using a two-crystal X-ray interferometer was studied aiming at in vivo observation in the future. In a preliminary study, the two-crystal X-ray interferometer was capable of generating fringes of 70% visibility using synchrotron X-rays.

Journal Article↗

Inhibition of human immunodeficiency virus type 1 replication by a bioavailable serine/threonine kinase inhibitor, fasudil hydrochloride.

Replication of human immunodeficiency virus type 1 (HIV-1) is regulated by a host transcription factor, nuclear factor kappaB (NF-kappaB). NF-kappaB belongs to a group of inducible transcription factors and its activity is regulated by multiple cellular signal transduction pathways, including kinases. These kinases are known to be involved in signal-induced NF-kappaB activation and in the induction of HIV-1 gene expression from latently infected cells. In this study we have examined the effect of a newly developed serine/threonine kinase inhibitor, fasudil hydrochloride (FH), on the replication of HIV-1. Although FH was initially developed as a compound that inhibited a myosin light chain kinase (MLCK) and had been approved for clinical use in the treatment of vasospasm after subarachnoid hemorrhage, this study shows its efficacy in blocking HIV-1 replication in latently infected patients. When FH was added to monocytic cell lines latently infected with HIV-1, U1 and OM10.1, the induction of HIV-1 replication by TNF-alpha was blocked at noncytotoxic doses. The IC50 values of HIV-1 induction by FH were 9.3 and 24 microM for U1 and OM10.1, respectively. Because FH could block TNF-alpha-induced, NF-kappaB-dependent gene expression, as examined by the transient luciferase expression assay, the effect of FH was considered to be due to the blocking of the signal transduction pathway of NF-kappaB activation. Although the in vivo effect of FH in blocking HIV-1 induction is not yet known, these findings indicate the feasibility of clinical use of FH and its derivatives in decreasing viral load to prevent clinical development of acquired immunodeficiency syndrome (AIDS) among HIV-1-infected individuals.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Surgical successful treatment of Cushing's syndrome in a pregnant patient complicated with severe cardiac involvement.

We encountered a case of a pregnant woman with adrenal causes of Cushing's syndrome who exhibited congestive heart failure as an initial symptom. Since the patient was also a diabetic, we treated her with high levels of diuretics and insulin. Echocardiography revealed a remarkable thickening of the left ventricle without asymmetric hypertrophy. The diagnosis of Cushing's syndrome caused by adrenal adenoma was confirmed by the endocrinological data and magnetic resonance imaging. The right adrenal adenoma was removed in the 28th week of pregnancy. After the operation, her congestive heart failure and hyperglycemia dramatically improved. Five weeks after the operation, she delivered a normal infant by caesarean section without complications. Only 4 months after delivery, the thickening of her left ventricle was normalized. We consider that the progression of her left ventricular hypertrophy induced by the changes in hemodynamic load during pregnancy may have been augmented by the excess of plasma cortisol. Operative therapy may be recommended for pregnant Cushing's syndrome patients with severe hypercortisolism complicating congestive heart failure.

Adenoma↗

Evaluation of thrombopoiesis in thrombocytopenic disorders by simultaneous measurement of reticulated platelets of whole blood and serum thrombopoietin concentrations.

To evaluate thrombopoiesis in thrombocytopenic disorders, we simultaneously determined reticulated platelet counts in whole blood by FACScan flow cytometry and serum thrombopoietin (TPO) concentrations by a sensitive sandwich ELISA. The subjects were 40 healthy volunteers and 45 thrombocytopenic patients. In idiopathic thrombocytopenic purpura (ITP), the percentage of reticulated platelets was significantly elevated (5.61 +/- 2.02%: mean +/- SD) relative to normal controls (2.17 +/- 0.90%), but serum TPO concentrations (1.91 +/- 1.27 fmol/l) did not differ significantly from the normal range (1.43 +/- 0.62 fmol/l). The patients with aplastic anemia (AA) had decreased reticulated platelet counts and markedly increased serum TPO concentrations (13.65 +/- 10.64 fmol/l). In thrombocytopenic patients with liver cirrhosis (LC), the absolute number of reticulated platelets (1.65 +/- 1.11 x 10(9)/l) decreased similarly that in AA. However, serum TPO concentrations (1.38 +/- 0.50 fmol/l) did not increase in contrast to AA. Our findings suggested a possible dual mechanism of thrombocytopenia in LC; that is, thrombocytopenia in LC results from the decreased TPO production primarily in the liver adding to an increase in platelet sequestration in the spleen.

Anemia, Aplastic↗

Operation of a Two-Crystal X-ray Interferometer at the Photon Factory.

A two-crystal X-ray interferometer for phase-contrast X-ray imaging is reported. Mechanical stability of less than 0.1 nm is required to operate the two-crystal interferometer. The feasibility of using such an interferometer at the Photon Factory using synchrotron radiation has been investigated. Interference fringes of 70% visibility were observed with 0.092 nm X-rays. This result indicates that the two-crystal X-ray interferometer can be applied to phase-contrast X-ray imaging.

Journal Article↗

Effects of dehydroepiandrosterone on proliferation of human aortic smooth muscle cells.

Dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) have been shown to be associated with the progression of coronary atherosclerosis in clinical and in vivo studies. However, the mechanisms responsible for the association have not been determined. In the present study, we found that DHEA influences the in vitro growth of vascular smooth muscle cells obtained from the human aorta (hASMC). The concentrations of DHEA ranging from 10(-8) M to 10(-6) M significantly stimulated the mitogenesis of hASMC in serum-free culture. On the other hand, 4 hrs of pretreatment with DHEA attenuated the fetal calf serum induced proliferative effect in a dose-dependent manner. However, the in vitro effects of DHEA on the mitogenesis observed in hASMC were not seen in rat-derived aortic smooth muscle cell lines (A10 cells). With respect to DHEAS, the hormone, at concentrations up to 10(-5) M did not affect the growth of either hASMC or A10 cells in vitro. The growth response of hASMC to DHEA in vitro was markedly affected by the culture conditions. The differential proliferative effects of DHEA on smooth muscle cells between rat and human are of interest. We conclude that the effects of DHEA on mitogenesis of hASMC may, at least in part, explain the association between DHEA and atherosclerosis.

Animals↗