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Biomedical subjects

Masanori Abe

Publications and source records attributed to Masanori Abe.

At least 19 recordsLinked to original sources

Clinicopathologic features of the severe form of acute type 1 autoimmune hepatitis.

BACKGROUND & AIMS: Acute onset autoimmune hepatitis (acute AIH) is difficult to diagnose by using serologic data. In addition, some patients with the severe form of acute AIH do not respond to immunosuppressive therapy and have a poor outcome. In this study, we analyzed the clinicopathologic features of patients who were diagnosed as having acute AIH. METHODS: Retrospective review of patients with presumed acute AIH at Ehime University Graduate School of Medicine was performed. RESULTS: In liver tissue, infiltrates in the portal area and plasma cell infiltration are more common in acute AIH compared with acute hepatitis caused by other causes. Patients with acute AIH who did not have severe jaundice at the time of diagnosis exhibited a very good response to corticosteroid therapy, despite lower titers of antinuclear antibody (ANA). Most patients with acute AIH with higher levels of bilirubin and titers of ANA in sera respond poorly to corticosteroid therapy. CONCLUSIONS: Histologic findings might be useful for the early diagnosis of acute AIH. Acute AIH patients with high levels of bilirubin and high titers of ANA in sera often do not respond to corticosteroid therapy.

Acute Disease↗

Identification of a chemical substructure that is immobilized to ferrite nanoparticles (FP).

Despite the wide utility of ferrite nanoparticles (FP), a methodology to conjugate heterologous molecules to FP is still limited and characterization of small molecule-conjugated FP is not well known. Here, we describe what kinds of proteins and amino acids are selectively immobilized onto FP when FP is synthesized in the presence of these molecules. Two-dimentional gel electrophoresis (2D SDS-PAGE) showed that proteins with low pI value were selectively bound to FP. Quantitative analyses using HPLC suggested that L-aspartic acid (Asp) and L-cysteine (Cys) were bound to FP selectively among natural amino acids examined. Additional analysis of compounds-conjugated FP revealed that selective binding of Asp to FP was attributed with its molecular structure. It was found that the substructure of amino acid-bound to FP specifically was composed of a defined chelation of two carboxyl groups separated by two carbon atoms as deduced from FT-IR measurement. Thus, we concluded that molecules possessing two carboxyl groups separated by two carbons were bound to FP spontaneously and selectively, which might enable the attachment of free functional groups onto the FP surface if their molecules have functional groups other than carboxyl groups. The resulting complex might be applicable as a chemical tag to immobilize various molecules onto FP.

Adsorption↗

High efficiency Hall effect micro-biosensor platform for detection of magnetically labeled biomolecules.

Detection of magnetically labeled biomolecules using micro-Hall biosensors is a promising method for monitoring biomolecular recognition processes. The measurement efficiency of standard systems is limited by the time taken for magnetic beads to reach the sensing area of the Hall devices. Here, micro-current lines were integrated with Hall effect structures to manipulate the position of magnetic beads via field gradients generated by localized currents flowing in the current lines. Beads were accumulated onto the sensor surface within seconds of passing currents through the current lines. Real-time detection of magnetic beads using current lines integrated with Hall biosensors was achieved. These results are promising in establishing Hall biosensor platforms as efficient and inexpensive means of monitoring biomolecular reactions for medical applications.

Biosensing Techniques↗

Clinical characteristics of autoimmune hepatitis in older aged patients.

BACKGROUND AND AIMS: Autoimmune hepatitis (AIH) is an inflammatory disease of the liver that usually develops in middle-aged women. However, due to the increasing aging of the population and better diagnostic facilities, AIH is now diagnosed in older patients as well. This analysis compared the clinical and pathologic characteristics of older and middle-aged patients with AIH. PATIENTS AND METHODS: Thirteen older patients with AIH (mean age, 75.0+/-5.3 years; range, 70-89 years) and 27 middle-aged patients (mean age, 51.3+/-5.8 years; range, 41-60 years) were included in this study. In addition, the use of different treatment regimens, including prednisolone therapy and ursodeoxycholic acid (UDCA), was examined. RESULTS: There were no significant differences in gender, complications of other autoimmune diseases, and liver function tests between groups. However, the degree of hepatic fibrosis was significantly higher in older patients compared with middle-aged patients (P<0.05). Four patients with AIH in the older age group were successfully managed by UDCA alone. CONCLUSION: This study shows that older patients with abnormal liver function should be checked for AIH. In addition, UDCA may be an effective drug for management of older patients with AIH.

Journal Article↗

Ethanol affects the generation, cosignaling molecule expression, and function of plasmacytoid and myeloid dendritic cell subsets in vitro and in vivo.

The influence of ethanol (EtOH) on multiple dendritic cell (DC) subsets, in the steady state or following their mobilization in vivo, has not been characterized. Herein, generation of mouse bone marrow-derived DC (BMDC) in response to fms-like tyrosine kinase 3 ligand was inhibited by physiologically relevant concentrations of EtOH with selective suppression of plasmacytoid (p)DC. EtOH reduced surface expression of costimulatory molecules (CD40, CD80, CD86) but not that of coinhibitory CD274 (B7-H1) on resting or CpG-stimulated DC subsets. Interleukin (IL)-12p70 production by activated DC was impaired. Consistent with these findings, EtOH-exposed BMDC exhibited a reduced capacity to induce naïve, allogeneic T cell proliferation and impaired ability to prime T cells in vivo. DC subsets freshly isolated from EtOH-fed mice were also examined. Liver DC, inherently immature and resistant to maturation, exhibited little change in their low surface cosignaling molecule expression, whereas splenic DC showed reduced expression of surface costimulatory molecules in response to CpG stimulation in vivo. These splenic DC elicited reduced naïve, allogeneic T cell proliferation in vitro, and the stimulatory capacity of resting but not CpG-activated liver DC was reduced by chronic EtOH administration. T cells from animals primed with EtOH-exposed DC produced elevated levels of IL-10 following ex vivo challenge with donor alloantigen. Thus, EtOH impairs cytokine-driven differentiation and function of myeloid DC and pDC in vitro. Hepatic DC from chronic EtOH-fed mice are less affected than splenic DC, which exhibit impaired functional maturation following CpG stimulation. These results indicate a potential mechanism by which alcohol consumption is associated with immunosuppression.

Alcohol-Induced Disorders↗

Heart allograft protection with low-dose carbon monoxide inhalation: effects on inflammatory mediators and alloreactive T-cell responses.

BACKGROUND: Carbon monoxide (CO), a byproduct of heme catalysis, has lately received considerable attention as a regulatory molecule in cellular and biological processes. CO has been shown to provide potent protection against a variety of tissue injuries. We hypothesized in this study that low concentration CO would be beneficial for organ allografts, which frequently undergo several types of injury such as ischemia/reperfusion, alloimmune reaction, and inflammation METHODS: The efficacy of low-dose CO was examined in a fully allogeneic LEW to BN rat heterotopic heart transplantation (HHTx) model. Recipients were kept in air or exposed to low-dose CO (20 ppm) for 14, 28, or 100 days after HHTx under short-course tacrolimus RESULTS: CO treatment (d0-28, 0-100) was remarkably effective in prolonging heart allograft survival to a median of >100 from 45 days in the air-control group, with significant reductions of arteritis, fibrosis, and cellular infiltration, including macrophages and T cells. CO inhibited intragraft upregulation of Th1 type cytokines (IL-2, IFNgamma), proinflammatory mediators (IL-1beta, TNFalpha, IL-6, COX-2), and adhesion molecule. Shorter CO exposure in early (0-13d) and late (14-28d) posttransplant periods also prolonged graft survival, with a significant inhibition of inflammatory mediators CONCLUSIONS: These results show that low dose CO inhalation protects heart allografts and can considerably prolong their survival. CO appears to function via multiple mechanisms, including direct inhibition of Th1 type cytokine production and regulation of inflammatory responses.

Administration, Inhalation↗

Endotoxin modulates the capacity of CpG-activated liver myeloid DC to direct Th1-type responses.

DC are believed to play important roles in the induction and regulation of immune responses in the liver, an organ implicated in peripheral tolerance. Since the liver is located downstream of the gut, it is constantly exposed to bacterial LPS. Our recent observations indicate that prior exposure to endotoxin modulates subsequent liver DC responses to this TLR4 ligand. In this study, we demonstrate that endotoxin modifies the capacity of mouse liver myeloid DC (MDC) activated by CpG (TLR9 ligand) to direct Th1-type responses. IL-12 production by liver MDC was significantly lower than that of spleen MDC following CpG or Imiquimod (R837; TLR7 ligand) activation in vitro. In addition, allogeneic T cells stimulated by CpG-activated liver MDC secreted significantly lower levels of IFN-gamma than T cells stimulated with CpG-activated spleen MDC. A similar effect on liver DC was observed in response to in vivo CpG administration. This effect may be explained by exposure of the DC to endotoxin, because LPS attenuated IL-12 production by CpG-stimulated liver MDC, both in vitro and in vivo. Moreover, attenuation of the response to CpG was not observed in liver MDC from TLR4-mutant (C3H/HeJ) mice, in which TLR4 signaling is impaired. These data suggest that endotoxin-induced 'cross-tolerance' to TLR ligands in liver DC may contribute to down-regulation of hepatic immune responses.

Adjuvants, Immunologic↗

Right coronary artery spasms triggered by mechanical compression during off-pump coronary artery bypass grafting surgery.

In this case report, we describe recurrent spasms of the right coronary artery with no apparent preexisting abnormal angiogram that caused second-degree atrioventricular (AV) block and inferior wall hypokinesis. These hemodynamic changes were induced by mechanical compression of the right coronary artery by a pericardium drain tube. From our experience, we should be aware that mechanical compression may trigger an exaggerated vasomotor response, leading to severe coronary artery spasms.

Aged↗

Aberrant halt of syringe pump motion: an improved system to prevent false setting of the syringe.

A syringe pump is used to inject precise doses of drugs having a strong action; for example, vasoactive drugs. Unexpected and undetected halt of a syringe pump can lead to potentially life-threatening complications. We experienced a sudden halt in the movement of a syringe pump (Terufusion syringe pump; Terumo, Tokyo, Japan) in two patients while administering norepinephrine in the intensive care unit (ICU). Fortunately, the patients had only transient hypotension, which was immediately detected and promptly treated, without any untoward sequelae. As a result of the occurrence of such cases, we conducted a detailed investigation of the causes of this sudden halt in the syringe pump. We could not reproduce the aberration of the syringe pump and thus could not specify the cause in the first patient. In the second patient, however, a false setting on the syringe was suspected to be the cause of the problem. In order to prove this, we tried to reproduce the situation where a syringe pump, due to a false syringe setting, abruptly terminated while giving a "syringe loss" warning, after a period of precise functioning. Once we had determined how a false setting of the syringe could occur without the syringe pump giving off an alarm from the onset, we collaborated with the Terumo Company to revise their current instruction manual to incorporate this as a warning. We also helped in the development of a new model, including a new safety feature that would prevent a false setting of the syringe from occurring at all. This new model was released in December 2003.

Coronary Artery Bypass↗

Urinary tract malformation and infection with hyperkalemia and decreased fractional excretion of potassium in an infant.

We describe an uncircumcised male infant treated for urinary tract infection who exhibited multiple hormonal and electrolyte abnormalities consistent with a diagnosis of transient pseudohypoaldosteronism. Successful treatment of the urinary tract infection was accompanied by the resolution of all hormonal and electrolyte abnormalities, including hyperaldosteronemia, hyperreninemia, hyponatremia and hyperkalemia. Radiographic examination revealed marked left dilatation of the renal pelvis and hydroureter but no vesicoureteral reflux. Owing to the possibilities of future renal scarring, decreased renal function, and hypertension, evaluation of urinary tract malformation and appropriate hormonal studies should be performed in infants with urinary tract infection and hyperkalemia.

Humans↗

Dendritic cell-based therapy as a multidisciplinary approach to cancer treatment: present limitations and future scopes.

Existence of residual cancers and recurrence of cancers are two major limitations of conventional therapies against cancers. A naturally-occurring defense system against tumor may be established in cancer patients by induction of antitumor immunity. Both polyvalent and tumor antigen-defined vaccines have been administered to cancer patients to accomplish this. However, the efficacy of these approaches is not promising. Dendritic cells (DCs) are regulator of the immune system. Antigens loaded on DCs (antigen-pulsed DCs) are able to induce immune responses when this can not be achieved by administration of antigens or vaccines only. Tumor antigen-pulsed DCs are now used for treatment of patients with cancers. But, it is unlikely that the present regimen of DC-based therapy would be an independent anticancer therapeutic approach. However, the therapeutic potentials of tumor antigen-pulsed DCs can be accentuated in cancer patients if this immune therapy is performed as part of multidisciplinary therapeutic approaches. In this review, we will describe about the concept and limitations of the present regimen of tumor antigen-pulsed DC-based therapy in cancer patients. We will further discuss how DC-based therapy can be applied as a multidisciplinary approach to cancer treatment.

Antigen Presentation↗

Dexamethasone preferentially suppresses plasmacytoid dendritic cell differentiation and enhances their apoptotic death.

Plasmacytoid dendritic cells (pDC) are an important source of type-1 interferon (IFN) following microbial infection and also play key roles in the induction of innate and adaptive immune responses. Here, we show that the glucocorticoid (GC) dexamethasone (Dex) strikingly reduces pDC (and myeloid DC) numbers in secondary lymphoid tissue and liver of normal and hematopoietic growth factor-mobilized mice and suppresses pDC differentiation from bone marrow precursors in vitro. Moreover, the apoptotic death of pDC in vitro was enhanced by exposure to Dex. Notably, however, Toll-like receptor 9 expression and virally induced IFNalpha production by residual pDC from Dex-treated animals were unaffected. Thus, whereas marked reduction in absolute numbers of pDC by GC may predispose to viral infection, often associated with GC-mediated immunosuppression, reductions in pDC and IFNalpha production may contribute to the beneficial effects on GC observed in systemic autoimmune disease, in which that both pDC and IFNalpha have been implicated.

Animals↗

A new method of biosensing with 1 microl of Escherichia coli suspension using atomic force microscopy.

We developed a new method for detecting bacterial cells from 1-mul samples with atomic force microscopy (AFM). The use of a parafilm surface as a sample palette was effective for reacting small amounts of samples with an AFM probe. This was due to the parafilm's hydrophobic, semitransparent, and nonadhesive surface. In this way, all processes, such as the surface functionalization of a cantilever and the adhesion of Escherichia coli cells to a cantilever, were easily completed. In addition, we succeeded in detecting cell adsorption on the same AFM cantilever by both the drive mode and the thermal mode. The resonance frequency shift caused by cell adhesion was clearly detected by the two modes for the first time. Our data indicated the potential of applying AFM nanobiosensing to extremely small amounts of samples.

Bacterial Adhesion↗

Low TLR4 expression by liver dendritic cells correlates with reduced capacity to activate allogeneic T cells in response to endotoxin.

Signaling via TLRs results in dendritic cell (DC) activation/maturation and plays a critical role in the outcome of primary immune responses. So far, no data exist concerning TLR expression by liver DC, generally regarded as less immunostimulatory than secondary lymphoid tissue DC. Because the liver lies directly downstream from the gut, it is constantly exposed to bacterial LPS, a TLR4 ligand. We examined TLR4 expression by freshly isolated, flow-sorted C57BL/10 mouse liver DC compared with spleen DC. Real-time PCR revealed that liver CD11c+CD8alpha- (myeloid) and CD11c+CD8alpha+ ("lymphoid-related") DC expressed lower TLR4 mRNA compared with their splenic counterparts. Lower TLR4 expression correlated with reduced capacity of LPS (10 ng/ml) but not anti-CD40-stimulated liver DC to induce naive allogeneic (C3H/HeJ) T cell proliferation. By contrast to LPS-stimulated splenic DC, these LPS-activated hepatic DC induced alloantigen-specific T cell hyporesponsiveness in vitro, correlated with deficient Th1 (IFN-gamma) and Th2 (IL-4) responses. When higher LPS concentrations (> or =100 ng/ml) were tested, the capacity of liver DC to induce proliferation of T cells and Th1-type responses was enhanced, but remained inferior to that of splenic DC. Hepatic DC activated by LPS in vivo were inferior allogeneic T cell stimulators compared with splenic DC, whereas adoptive transfer of LPS-stimulated (10 ng/ml) liver DC induced skewing toward Th2 responses. These data suggest that comparatively low expression of TLR4 by liver DC may limit their response to specific ligands, resulting in reduced or altered activation of hepatic adaptive immune responses.

Animals↗

Prolonged protective effect of short daily hemodialysis against dialysis-induced hypotension.

BACKGROUND/AIMS: Short daily hemodialysis (HD) has a protective effect against dialysis-induced hypotension (DIH). We examined whether this effect extends beyond the treatment period. METHODS: We analyzed clinical variables in 6 patients (5 with diabetes mellitus) who underwent conventional hemodialysis (CHD) for 4 h three times weekly for 12 weeks; then short daily HD for 2 h six times weekly for 12 weeks, and then 12 more weeks of CHD. All patients had been given vasopressors for severe DIH. RESULTS: The severe DIH disappeared during the short daily HD. There were significant decreases in body weight (BW), cardiothoracic ratio (CTR), blood pressure (BP), normal saline solution (NSS) amount (62.8 +/- 26.4 vs. 9.8 +/- 7.4 ml/session, p < 0.05), frequency (0.60 +/- 0.26 vs. 0.10 +/- 0.07 infusions/session, p < 0.05) and postdialysis atrial natriuretic peptide (ANP) (176.8 +/- 56.4 vs. 104.8 +/- 42.3 pg/ml, p < 0.05). Weekly ultrafiltration volume (6.3 +/- 0.9 vs. 7.9 +/- 0.7 l, p < 0.05) was significantly higher during the short daily HD period than during the first CHD period. The vasopressor treatment was therefore stopped or reduced in all patients during the short daily HD period. Because DIH recurred in the second CHD period despite a significant increase in BP, the vasopressor treatment was resumed in 5 patients. BW, CTR, NSS infusion amount and frequency, or postdialysis ANP did not differ significantly between the short daily HD and second CHD periods. CONCLUSIONS: The protective effect of short daily HD against DIH lasted more than 12 weeks after the treatment ended. We therefore conclude that temporary short daily HD is useful for preventing DIH.

Aged↗

Therapeutic efficacy of decreased nitrite production by bezafibrate in patients with primary biliary cirrhosis.

BACKGROUND: The therapeutic efficacy of bezafibrate, a hypolipidemic drug, has been shown in patients with primary biliary cirrhosis (PBC) in some pilot studies; however, little is known regarding the mechanism of action of bezafibrate in PBC. This study was conducted to evaluate the therapeutic efficacy, as well as to gain insight about the possible mechanism of action, of bezafibrate in PBC. METHODS: Sixteen patients with PBC were administered with bezafibrate (400 mg/day) either with (n = 10) or without ursodeoxycholic acid (UDCA; n = 6). The peripheral blood of these patients was collected before and at different times after therapy commencement, and antigen-presenting dendritic cells (DCs) were then cultured. The DCs were enriched and cultured with Staphylococcus aureus Cowan strain-1 for 48 h to evaluate their capacity to produce nitrite. RESULTS: One month after the start of bezafibrate therapy, the serum levels of alkaline phosphatase (P = 0.0005), gamma-glutamyl transpeptidase (P = 0.0006), total cholesterol (P = 0.0072), and immunoglobulin M (P = 0.0281) were decreased significantly compared to those before patients started bezafibrate therapy. The levels of nitrite produced by DCs decreased in all patients with PBC within 1 month of commencement of bezafibrate therapy. Moreover, decreased nitrite production by DCs was also seen when nitrite production was evaluated 1 year after the start of bezafibrate therapy. CONCLUSIONS: This study reconfirms the therapeutic efficacy of bezafibrate in patients with PBC, including those with UDCA-resistant PBC. Downregulation of nitrite production by DCs may have some relationship with the therapeutic efficacy of bezafibrate; however, further study will be needed to clarify whether or not the antiinflammatory activity of bezafibrate is mediated through nitrite production.

Adult↗