PubMed Health⌕ Search

Biomedical subjects

D Suzuki

Publications and source records attributed to D Suzuki.

At least 19 recordsLinked to original sources

Microdamage and altered vascularity at the enthesis-bone interface provides an anatomic explanation for bone involvement in the HLA-B27-associated spondylarthritides and allied disorders.

OBJECTIVE: To describe the basis for entheseal-associated bone disease in the spondylarthritides, by analyzing microanatomic and histopathologic relationships between soft tissue, bone cortex, and adjacent trabeculae. METHODS: Serial sections from 52 entheses were examined; these entheses encompassed small and large insertions in the upper limb (n = 21), lower limb (n = 27), and spine (n = 4) from 60 cadavers. Enthesis microdamage (fissuring) as well as vascular and reparative changes were evaluated. Contact radiographs were used to ascertain the relationship between entheses and the trabecular network. RESULTS: At virtually all fibrocartilaginous entheses, the deep cortical boundary was extremely thin (typically 50-600 microm) or indistinguishable, and 96% of entheses had small holes in the cortical shell (typically 100-400 microm wide). Such regions were frequent sites of bone formation and renewal (96%) and microdamage (31%); these changes were more common in the lower limb. The presence of blood vessels near holes in the cortical shell was common; in 85% of attachments, blood vessels were present on the soft tissue side of the enthesis. Highly orientated trabeculae were more obvious in the lower limb than the upper limb (59% versus 29%). CONCLUSION: The trabecular network supporting the cortical shell is an integral part of the enthesis, transferring load to an extensive skeletal region. In many cases, tendons/ligaments are anchored directly to such networks. This functional integration is associated with microdamage and repair at the hard tissue-soft tissue interface. These findings have implications for understanding bone involvement in SpA and for the SpA concept in general, especially the hypothesis that enthesis-bone architecture may be important in disease initiation.

Aged↗

Regional variations in human patellar trabecular architecture and the structure of the proximal patellar tendon enthesis.

Proximal patellar tendinopathy occurs as an overuse injury in sport and is also characteristic of ankylosing spondylitis patients. It particularly affects the posteromedial part of the patellar tendon enthesis, although the reason for this is unclear. We investigated whether there are regional differences in the trabecular architecture of the patella or in the histology of the patellar tendon enthesis that could suggest unequal force transmission from bone to tendon. Trabecular architecture was analysed from X-rays taken with a Faxitron radiography system of the patellae of dissecting room cadavers and in magnetic resonance images of the knees of living volunteers. Structural and fractal analyses were performed on the Faxitron digital images using MatLab software. Regional differences at the enthesis in the thickness of the uncalcified fibrocartilage and the subchondral plate were evaluated histologically in cadaveric material. The radiological studies showed that the quantity of bone and the apparent trabecular thickness in the patella were greatest medially, and that in the lateral part of the patella there were fewer trabeculae which were orientated either antero-posteriorly or superiorly inferiorly. The histological study showed that the uncalcified fibrocartilage was most prominent medially and that the subchondral plate was thinner laterally. Overall, the results indicate that mechanical stress at the proximal patellar tendon enthesis is asymmetrically distributed and greater on the medial than on the lateral side. Thus, we suggest that the functional anatomy of the knee is closely related to regional variations in force transmission, which in turn relates to the posteromedial site of pathology in proximal patellar tendinopathy.

Adult↗

Role of E-cadherin molecules in spheroid formation of hepatocytes adhered on galactose-carrying polymer as an artificial asialoglycoprotein model.

The role of E-cadherin in the spheroid formation of hepatocytes adhered on the poly(N-p-vinylbenzyl-D-lactonamide) (PVLA) as a model ligand for asialoglycoprotein receptors (ASGP-R) of hepatocytes was studied. Expression of E-cadherin was increased in round hepatocytes adhered on a high-coating density of PVLA (100 microg/ml), and also in flat ones adhered on a low-coating density of PVLA (1 microg/ml) in the presence of epidermal growth factor (EGF). Hepatocyte spheroids formed on the high-coating density of PVLA in the presence of EGF after 48 h were inhibited by an anti-E-cadherin monoclonal antibody (ECCD-1). From immunofluorescence and confocal laser microscopy, E-cadherin was localized in the intercellular boundaries and concentrated at the inside surface of aggregated cells. As a result, E-cadherin could play an important role in hepatocyte assembly.

Asialoglycoproteins↗

The role of CD4 and CD8 cytotoxic T lymphocytes in the formation of viral vesicles.

BACKGROUND: Herpetic vesicles caused by herpes simplex virus and varicella zoster virus, and hydroa vacciniforme (HV) are characterized by umbilicated vesicule formation. OBJECTIVES: To understand the histogenesis of umbilicated vesicles in herpetic vesicles and HV, we demonstrated the presence of the virus-associated molecules in the lesions, and the pathogenic role of cytotoxic T-lymphocyte (CTL) immune responses. METHODS: Phenotyping of infiltrating cells was carried out in biopsy specimens from herpes simplex, varicella, herpes zoster and HV, and compared with nonviral contact dermatitis. Viral antigens and Epstein-Barr virus-encoded small nuclear RNA (EBER) were detected by immunostaining and by in situ hybridization, respectively. Infiltrating CTLs expressing granzyme B and granulysin were determined by double immunostaining using confocal laser scanning microscopy. RESULTS: In all herpetic vesicles, the corresponding viral antigens were observed in the cytopathic keratinocytes, and infiltration of lymphoid cells was present in the upper dermis and around the vessels. In all HV lesions studied, EBER+ T cells made up 5-10% of the dermal infiltrates and the dermal infiltrates contained almost no CD56 cells. CTLs expressing granzyme B and granulysin were present in both herpetic and HV lesions, in which they made up 10-30% of the total dermal infiltrates, whereas they comprised less than 5% of the infiltrates of biopsy specimens from nonviral contact dermatitis. Confocal laser microscopic examination demonstrated that both CD4+ and CD8+ T cells expressed granzyme B and granulysin. CONCLUSIONS: CD4+ and/or CD8+ CTLs reactive to the virus-infected cells might be responsible for the histogenesis of herpetic and HV lesions characterized by umbilicated vesicles.

Antigens, Differentiation, T-Lymphocyte↗

Renal in situ hybridization studies of extracellular matrix related molecules in type 1 diabetes mellitus.

BACKGROUND/AIM: Progressive expansion of mesangial matrix and glomerular basement membrane thickening represent alterations in the balance between synthesis and degradation of glomerular extracellular matrix (ECM) protein and are hallmarks of diabetic nephropathy. In order to elucidate the basis for this imbalance between the synthesis and the degradation of ECM in renal tissues from patients of type 1 diabetes mellitus (type 1D) with diabetic nephropathy (DN), we examined the expression of alpha1 chain of type IV collagen (IV-C), matrix metalloproteinase-2 and -3 (MMP-2, MMP-3), tissue inhibitor of metalloproteinase-1 (TIMP-1) and beta-actin mRNA using a high-resolution in situ hybridization with digoxigenin-labeled oligonucleotide. METHODS: Patients were divided into two groups based on both of degree of mesangial expansion using electron microscopic point counting morphometric methods and duration of type 1D: 7 'fast-track' patients were selected for their very rapid development of DN structural changes and 8 'slow-track' patients for their very slow development of DN structural changes. Seven normal human kidney (NHK) tissues were used as controls. RESULTS: Positive cells for each mRNA were observed in glomerular resident cells, including glomerular mesangial, epithelial and endothelial cells and cells of Bowman's capsule. The percentage of glomerular cells positive for IV-C, MMP-2 and MMP-3 mRNA was significantly greater in the 'slow-track' vs. 'fast-track' patients. No significant differences in percentage positive cells was seen for beta-actin mRNA. Furthermore, to elucidate the total number of positive cells per glomerulus for each mRNA, we estimated total cell number of glomerulus using morphometric techniques on light microscopy tissues. The total cell number per glomerulus was significantly greater in 'fast-track' than that in 'slow-track' patients and NHK. The total number of positive cells per glomerulus for MMP-2 in NHK was significantly greater than that in 'slow-track' and 'fast-track' patients. CONCLUSIONS: Thus, IV-C, MMP-2, MMP-3 and TIMP-1 mRNA are expressed in resident glomerular cells in renal tissues from NHK and type 1D. Glomerular alterations in these in situ mRNA expressions sufficient to explain ECM accumulation and DN risk were not uncovered. These largely negative results could be due to methodologic quantitative imprecision or could indicate that post-translational differences account for ECM imbalance in DN. However, these studies make it clear that unraveling the nature of the ECM production/removal imbalance in DN will require careful consideration of alterations in glomerular cell number.

Adult↗

Specific tissue distribution of megsin, a novel serpin, in the glomerulus and its up-regulation in IgA nephropathy.

Mesangial cells play critical roles in maintaining a structure and function of the glomerulus. We previously cloned a novel mesangium-predominant gene, megsin, a new serine protease inhibitor. To clarify localization and roles of megsin protein, we raised polyclonal antibodies to megsin. By immunohistochemistry, megsin protein was specifically identified in the mesangial area. The amount of megsin protein was increased in glomeruli of patients with IgA nephropathy than in those of normal individuals and of patients with minimal change nephrotic syndrome or membranous nephropathy, suggesting a pathophysiological role of megsin as a functional modulator of mesangial functions in situ.

Amino Acid Sequence↗

Surface molecules essential for positive selection are retained but interfered in thymic epithelial cells after monolayer culture.

It has been reported that the three-dimensional structure of thymic epithelial cells (TECs) is responsible for thymic positive selection but that this ability disappears when TECs are cultured in monolayer. These results have supported the hypothesis that certain TEC-specific molecules are extinguished during monolayer culture. In this study, using MHC class II-restricted T-cell receptor transgenic mice, we demonstrated that preselected CD4(+)8(+) (DP) thymocytes were inhibited from developing into CD4(+)8(-) (CD4SP) cells in reaggregate thymus organ culture with monolayer-cultured TECs, but this inhibition was removed when TECs were cultured in monolayer with protein synthesis inhibitor or when the cultured TECs were treated with fixative. These results seem to be inconsistent with the previous hypothesis and indicate that monolayer culture allows TECs to retain the surface molecules necessary for positive selection but interferes with their function, which must be sustained for three dimensional structure.

Animals↗

Cloning of rodent megsin revealed its up-regulation in mesangioproliferative nephritis.

BACKGROUND: We recently cloned a new human mesangium-predominant gene, megsin. Megsin is a novel member of the serine protease inhibitor (serpin) superfamily. To elucidate functional roles of this gene, we cloned megsin in rodents and investigated its role in a rat nephritis model. METHODS: Megsin homologues were cloned from cultured rat and mouse mesangial cDNAs utilizing polymerase chain reaction (PCR) with degenerative primers. Expression of megsin in three different types of resident glomerular cells was investigated by PCR. Levels of megsin mRNA expression at various time points in the anti-Thy1 rat nephritis model were studied by semiquantitative PCR and Northern blotting analysis. In order to investigate megsin protein expression in anti-Thy1 nephritis rats, we raised antibody against rat megsin-specific synthetic peptide, with which immunohistochemical studies were performed. RESULTS: Rat and mouse megsins were composed of 380 amino acids, which revealed 75.3 and 73.9% identity, respectively, with human megsin at the amino acid level. Characteristic features as an inhibitory serpin were conserved in both rat and megsin megsins. PCR analysis revealed expression of megsin in cultured mesangial cells but not in glomerular epithelial or endothelial cells. In anti-Thy1 nephritis rats, semiquantitative PCR and Northern blotting showed that expression of megsin mRNA was up-regulated in glomeruli at day 8. Immunohistochemical studies demonstrated the prominent accumulation of megsin in glomeruli at the same time point. Megsin was mainly localized in mesangial area. The megsin expression level returned to the basal level at day 28. CONCLUSION: Sequences of megsin were well conserved among different species. Rat megsin was also predominantly expressed in mesangial cells. Expression of megsin was up-regulated at the peak of hypercellularity and matrix accumulation in the mesangioproliferative glomerulonephritis model, suggesting that megsin may participate in the process of glomerulosclerosis by modulating extracellular matrix deposition or cell survival.

Amino Acid Sequence↗

Impedance magnetocardiogram.

We have developed an impedance magnetocardiogram (IMCG) system to detect the change of magnetic field corresponding to changes in blood volume in the heart. A low magnetic field from the electrical activity of the human heart--the so-called magnetocardiogram (MCG)--can be simultaneously detected by using this system. Because the mechanical and electrical functions in the heart can be monitored by non-invasive and non-contact measurements, it is easy to observe the cardiovascular functions from an accurate sensor position. This system uses a technique to demodulate induced current in a subject. A flux-locked circuit of a superconducting quantum interference device has a wide frequency range (above 1 MHz) because a constant current (40 kHz) is fed through the subject. It is shown for the first time that the system could measure IMCG signals at the same time as MCG signals.

Adult↗

Limited effect of chromatin remodeling on D(beta)-to-J(beta) recombination in CD4+CD8+ thymocyte: implications for a new aspect in the regulation of TCR beta gene recombination.

We have generated mutant mice in which TCR beta chain enhancer (E(beta)) was replaced with the TCR alpha chain enhancer (E(alpha)). Using this mouse model, we analyzed (i) recombination status of the TCR beta chain genes after functional V(D)J rearrangements occurred in the first allele during double-negative (DN)-to-double-positive (DP) transition and (ii) involvement of E(beta) for the expression of rearranged TCR beta chain genes. Our data show that E(alpha) substituted for E(beta) function to express a similar extent of TCR beta chains exactly at the same time as did E(beta) (CD25+CD44- DN stage), although the proportion of TCR beta+ cells at this stage was low in mutant mice. At the DP stage, germline transcription and histone acetylation of D(beta)-J(beta) loci were detectable at a high degree in both mutant and wild-type mice. However, DP cells in mutant mice retained the germline D(beta)-J(beta) configuration at a higher frequency than that of wild-type mice, whereas both DP cells expressed TCR beta chains to a similar extent. These data suggest that chromatin opening has a limited impact on D(beta)-to-J(beta) recombination at the DP stage and that E(alpha) is functionally equivalent to E(beta) in promoting expression of functionally rearranged TCR beta chain genes through DN-to-DP transition.

Animals↗

[Suppressive effect of lansoprazole on anti-Candida activity of murine macrophages].

This study investigated the influences of lansoprazole (AG1749), a proton pump inhibitor (PPI), and its active derivative (AG2000) on Candida albicans growth and the anti-Candida activity of macrophages. Under concentration of 100 microM, AG1749 and AG2000 had no effect on Candida growth. Murine peritoneal macrophages inhibited the growth of C. albicans in vitro. AG2000 suppressed the anti-Candida activity of macrophages dose-dependently, but AG1749 didn't. The suppressing activity of AG2000 for macrophages was neutralized by adding a SH-compound (L-cysteine) in the medium. This suggests that AG2000 may suppress macrophage function in a similar manner with inhibition of proton pump through binding to SH-molecules. When macrophages were preincubated with AG2000 for 1 hr and washed, their anti-Candida activity remained to be partially inhibited for 14 hrs. These results were discussed in relation to the pathogenesis of esophageal candidiasis.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Carbonyl stress.

Explore the source record for details and available documents.

Diabetic Nephropathies↗

Analysis of a uranium solution for evaluating the total number of fissions in the JCO criticality accident in Tokai-mura.

The uranium solution in the precipitation tank in the JCO's uranium conversion facility was analyzed in order to evaluate the total number of fissions in the criticality accident. Two analytical groups at JAERI performed chemical analyses independently in order to check the validity of the results: the concentration of the fission products (95Zr, 99Mo, 103Ru, 131I, 140Ba, etc), uranium, boron and impurity elements in the solution. The analytical results obtained by the two groups were almost in agreement within the analytical error. The number of fissions per one gram of uranium in the accident was determined to be (1.5 +/- 0.1 ) x 10(14). Also, the total number of events was evaluated to be (2.5 +/- 0.1) x 10(18) fissions using the total amount of uranium (16.6 kg) fed into the precipitation tank at the accident.

Chemical Precipitation↗

Evaluation of renal biopsy samples of patients with diabetic nephropathy.

OBJECTIVE: To evaluate the usefulness of renal biopsy in the overall management of patients with diabetes mellitus (DM), we examined the relationship between the clinical parameters and histopathological findings of renal biopsy samples. METHODS: Renal biopsy specimens were obtained from 109 type 2 diabetic patients with proteinuria. Samples were divided into the following two groups: Diabetic Nephropathy (DN) group (n=80) had typical diabetic lesions without other renal diseases, complication group (n=29) had diabetic lesions with other renal diseases. Furthermore, DN group was subdivided into two subgroups: slow progressive group (SP group, n=32), the level of serum creatinine (s-Cr) was normal at the time of renal biopsy and three years after renal biopsy, and fast progressive group (FP group, n=14), the level of s-Cr was normal at the time of renal biopsy but more than doubled three years after renal biopsy. RESULTS: The level of total protein was significantly lower and HbA1c significantly higher in the DN group than in the Complication group. However, other clinical parameters were not significantly different between the two groups. Urinary protein, systolic and diastolic blood pressure in FP group were significantly higher than in SP group. The percentage of sclerotic glomeruli, the severity of mesangial expansion, tubular injury and cell infiltration were significantly greater in FP than in SP group. CONCLUSIONS: Our results indicated that a complete evaluation of renal pathology in DM could not be made by clinical parameters only, and that the progression of DN could be accurately predicted by histopathological evaluation. Therefore, this study emphasizes the importance of renal biopsy in the overall management of patients with DM and/or DN.

Adult↗

[Two cases of episodic angioedema associated with eosinophilia].

We experienced two cases of limb edema of unknown pathogenesis. No evidence was found concerning involvement of the kidneys, heart of other visceral organs. Case 1 was 22-year-old woman. Her white blood cell count increased to 13,100/microliter with 65.0% eosinophils. Case 2 was a 27-year-old woman. Her white blood cell count increased to 23,300/microliter with 67.0% eosinophils. In these cases, extensive diagnostic evaluations revealed no evidence of atopy, neoplasms, collagen-vascular disease, or parasitic infestation. We diagnosed these cases as episodic angioedema with eosinophilia. In both cases, the angioedema improved gradually in parallel with a decrease in the white blood cell count. This disorder is very rare, but it is very important to consider it in differential diagnosis especially for nephrologists.

Adult↗

[A case of antiphospholipid antibody syndrome with variable renal histological change despite of poor changes in urinalysis].

We experienced a case of lupus nephritis with antiphospholipid antibody syndrome. A renal biopsy specimen from this patient showed various renal histological changes, but the results of urinalysis were almost normal. The patient was a 56-year-old woman diagnosed as having systemic lupus erythematosus with antiphospholipid antibody syndrome in 1983. In 1998, she had diarrhea and blood gas analysis showed metabolic acidosis. Therefore, she was admitted to our hospital and underwent renal function examination. The glomerular filtration rate was reduced(GFR: 40/ml/min), but urinalysis was almost normal. To examine her renal dysfunction, we performed open renal biopsy. Her renal tissues showed global glomerular sclerosis, mesangial cell proliferation and infiltration of cells in the tubulointerstitial area(WHO II). Furthermore, some arterioles showed organized thrombus formation and recanalization due to the antiphospholipid antibody syndrome. Renal biopsy of patients with lupus nephritis is useful not only for precise diagnosis, but also for the selection of appropriate treatment.

Antiphospholipid Syndrome↗