[Hyperlipidemia and cardiovascular disease].
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Aged↗
Biomedical subjects
M Kubo
Publications and source records attributed to M Kubo.
[Clinical characteristics of hypertriglyceridemia-induced pancreatitis].
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Animals↗
Immunogenicity of human amniotic membrane in experimental xenotransplantation.
PURPOSE: The immunogenic characterization of amniotic membrane is still unknown. This study was designed to examine the immunogenicity of human amniotic membrane, by using experimental xenotransplantation models. METHODS: Anti-human class I, class II, and Fas ligand monoclonal antibodies were used against cryopreserved amniotic membrane and cell viability tested for cryopreserved amniotic membrane. Amniotic membranes were then transplanted to the limbal area, intracorneal space, and under the kidney capsule. The scores of transparency and neovascularization after transplantation were recorded by slit lamp microscopy. Host cell infiltration was examined by hematoxylin-eosin or immunohistochemical staining. Control grafts were transplanted human cryopreserved skin grafts. RESULTS: Strong class I expression was observed in amniotic epithelium, mesenchymal cells, and fibroblasts in cryopreserved amniotic membrane. Some fibroblast cells unexpectedly expressed class II antigen. Fas ligand-positive cells were also detected in mesenchymal cells of amniotic stroma. Approximately 50% of epithelial cells of amniotic membrane cryopreserved for several months were still viable. In limbal transplantation, although some CD4(+) and CD8(+) T cells surrounded the amniotic graft, the response was mild. In intracorneal transplantation, all grafted amniotic membranes were accepted and clear, without host cell infiltration. In contrast, all skin grafts were rejected within 3 weeks after intracorneal transplantation. In amniotic membrane transplantation under the kidney capsule, extremely few host vessels and cells infiltrated the amniotic membrane; however, more host cells infiltrated the skin tissues under the kidney capsule. CONCLUSIONS: Amniotic membrane seems to be immune-privileged tissue and to contain some immunoregulatory factors, including HLA-G and Fas ligand. The amniotic membrane may be useful to supplement corneal collagen, and it may be applied not only to the ocular surface but also intracorneally.
Amnion↗
[Dural arteriovenous fistula of the anterior cranial fossa associated with occlusion of the internal carotid artery: a case report].
We reported a case with dural arteriovenous fistula (dAVF) of the anterior cranial fossa associated with occlusion of the left cervical internal carotid artery. A 73-year-old man was admitted with total aphasia and right hemiparesis. Computed tomography showed an ischemic lesion of the left cerebral hemisphere and old infarction of the left occipital lobe. Angiography revealed occlusion of the left cervical internal carotid artery and dAVF of the anterior cranial fossa, fed by the left middle meningeal and the right anterior ethmoidal artery. Follow-up angiography revealed spontaneous recanalization and severe arteriosclerosis of the left internal carotid artery. After marked improvement of neurological deficits, the patient underwent surgical clipping of the draining veins to occlude the dAVF of the anterior cranial fossa. We speculated that marked development of the collateral circulation from the external carotid system might result in the occurrence of dAVF of the anterior cranial fossa.
Aged↗
[Historical investigation of dentifrice in China].
A herbal literature survey was carried out on data concerning historical pharmacognostical changes of "dentifrice" in China and how diseases of the teeth and gums had been treated there in ancient times. It had been considered to be a matter of utmost importance that to prevent teeth from decaying, only the brushing of teeth with a toothbrush was necessary. Over time, various tooth agents have been found to treat oral diseases the teeth and gums. Glycyrrhizae Radix, Ginseng Radix, Scutellariae Radix, Menthae Herbal, and salt were widely used materials. Investigations from all approaches are being carried out to develop remedies for oral diseases, including Kampo medicine and the pharmacological effects of numerous crude drugs. When tracing the pharmacognostical changes of dentifrice in ancient China, we felt wonder at and admiration for the abundance of clinical experiences described in the old herbal and medical literature we researched.
China↗
Novel role of phosphatidylinositol 3-kinase in CD28-mediated costimulation.
Ligation of the CD28 surface receptor provides a major costimulatory signal for full scale T cell activation. Despite extensive studies, the intracellular signaling pathways delivered by CD28 ligation are not fully understood. A particularly controversial matter is the role of phosphatidylinositol 3-kinase (PI3K) in CD28-mediated costimulation. It is known that the binding site for PI3K and Grb-2 lies nested within the YMNM motif of the CD28 cytoplasmic domain. To elucidate the role of PI3K during CD28-mediated interleukin-2 (IL-2) production, CD28 YMNM point and deletion mutants were expressed in Jurkat cells. We then measured IL-2 promoter activation after CD28 ligation. Our results showed that the Y189F mutant, which disrupts binding by PI3K, and the YMNM deletion mutant both demonstrated reduced but significant activity for IL-2 promoter activation. In contrast, the N191A mutant, which retains PI3K binding ability, resulted in a complete abrogation of activity, suggesting that PI3K mediates a negative effect upon transcriptional activation of the IL-2 gene. Consistent with this idea, we found that the addition of a PI3K pharmacological inhibitor augmented IL-2 promoter activity, whereas coexpression of a constitutively active form of PI3K reduced this activity. Taken together, these data indicate that PI3K, when associated with the YMNM motif, may act as a negative mediator in CD28-mediated IL-2 gene transcription.
Amino Acid Motifs↗
[Huge aneurysm of aortic coronary cusp and Valsalva sinus secondary to Behçet's disease].
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Aortic Aneurysm↗
Interleukin-15 induces rapid tyrosine phosphorylation of STAT6 and the expression of interleukin-4 in mouse mast cells.
Interleukin (IL)-4 plays an important role in the differentiation of naive T helper (Th) cells into Th2. Mast cells can produce a significant amount of IL-4 and have been proposed to play a major role in the induction of Th2 responses. Recently, it has been reported that mast cells have a distinct IL-15 receptor system different from that of T or natural killer cells. In the present study, we demonstrated that IL-15 induced IL-4 production from a mouse mast cell line, MC/9, and bone marrow-derived mast cells. IL-4 mRNA expression was increased by IL-15, suggesting that IL-15 promotes IL-4 expression at the transcriptional level. In these mast cells, signal transducer and activator of transcription (STAT) 6 were rapidly tyrosine-phosphorylated in response to IL-15. In MC/9 cells, the expression of a C-terminally truncated dominant negative form of STAT6 significantly suppressed the IL-4 mRNA up-regulation by IL-15, suggesting that STAT6 activation is essential for the IL-15-mediated IL-4 production. Additionally, tyrosine phosphorylation of Tyk2 was rapidly increased by IL-15 treatment in this cell line. Altogether, our results suggest that IL-15 plays an important role in stimulating early IL-4 production in mast cells that may be responsible for the initiation of Th2 response.
Animals↗
Suppressive effect of the herbal medicine Oren-gedoku-to on cyclooxygenase-2 activity and azoxymethane-induced aberrant crypt foci development in rats.
The present study is part of a program to obtain effective chemopreventive agents with low toxicity from medicinal herbs and traditional herbal medicines. We previously reported that Oren (Coptidis rhizoma) and Ogon (Scutellariae radix) inhibit azoxymethane (AOM)-induced aberrant crypt foci (ACF) formation. In the present investigation, we found Sanshishi (Gardeniae fructus) and the traditional herbal medicine Oren-gedoku-to (OGT), composed of Ogon, Oren, Sanshishi and Obaku, also have preventive potential. Sanshishi and OGT decreased the numbers of ACF to 25.2 and 59.4% of the control value at 2% in the diet, respectively. Adverse effects, evidenced by body weight loss, were weaker with OGT than component herbs. To investigate their mechanisms of action, the influence on cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) activities was studied. Both OGT and Sanshishi inhibited COX-2 but not COX-1, this presumably contributing to their suppressive effects on ACF development. The results suggest that OGT may be useful for colon cancer chemoprevention in terms of efficacy and toxicity.
Animals↗
Synergism between the calmodulin-binding and autoinhibitory domains on calcineurin is essential for the induction of their phosphatase activity.
Elevation of the intracellular calcium concentration is necessary for cell growth and the activation of several lymphokine genes. The immunosuppressive drugs cyclosporin A and FK506 profoundly inhibit the calcium-dependent signaling pathway in T lymphocytes by interfering with the activity of the calcium/calmodulin (CaM)-dependent serine/threonine phosphatase, calcineurin (CN). Little is known, however, about how activation of CN enzyme activity or interaction with its substrate, nuclear factor of activated T cell (NF-AT), is regulated. We show here that the binding of CaM to CN may affect the conformation of CN at both the CaM-binding and the autoinhibitory (AI) domains and that this is critical for activation of CN to dephosphorylate NF-AT. Dissociation of the AI domain from the enzyme active site on CN leads to expose a binding site for NF-AT at the N terminus of CN and allows the CN binding to NF-AT. Since the cytoplasmic form of NF-AT can interact with CN mutants lacking enzyme activity, the interaction of the two molecules is independent of CN enzyme activity and occurs prior to the dephosphorylation of NF-AT. Dephosphorylation converts NF-AT from the cytoplasmic to the nuclear form by exposing the DNA-binding domain on NF-AT, and the nuclear form of NF-AT brings CN together into the nuclei. We therefore propose that the activation of CN by the CaM binding independently regulates the interaction with NF-AT and the dephosphorylation of NF-AT.
3T3 Cells↗
Immunohistochemical detection of apolipoprotein E within prion-associated lesions in squirrel monkey brains.
The interaction of various amyloid precursors and apolipoprotein E (apoE) is important for Congophilic amyloid formation. As for cerebral amyloidoses, although the correlation between amyloid beta protein (Abeta) and apoE in Alzheimer's disease (AD) has been clarified, the interaction of prion protein isoform (PrPsc) and apoE in several types of prion diseases (PDs) has not been examined in detail. ApoE colocalization has been confirmed in Congophilic PrPsc plaques, but to clarify the participation of apoE in the early stage of PDs, apoE deposition in immature lesions without Congophilic amyloid in PDs needs to be examined. In the present study two squirrel monkeys were inoculated with mouse PrPsc derived from sheep scrapie, and showed signs of severe spongiform degeneration. These lesions were immunohistochemically characterized as patchy perivacuolar and diffuse synaptic lesions without Congophilic amyloid. The central portion of the assemblies involving a few patchy perivacuolar lesions was detected by methenamine silver staining and appeared as a plaque-like lesion. ApoE was colocalized in all the plaque-like lesions and in half of the patchy perivacuolar lesions, but not in any diffuse synaptic lesions. These immunohistochemical characteristics indicated that apoE colocalization occurred in moderate mature lesions in PDs, and apoE might play an important role in the aggregation of PrPsc after a conformational change from cellular PrP isoform to PrPsc.
Amyloid beta-Peptides↗
Microperforate hymen at 27 years of age diagnosed with withdrawal bleeding and hysterofiberscopy.
Microperforate hymen is a congenital obstructive vaginal membrane with a tiny opening. It is usually detected long before menarche because of recurring vulvovaginitis and urinary tract infection. We report a case of microperforate hymen in a 27-year-old women presenting oligomenorrhea, in whom the location of the tiny opening on the hymenal membrane was detected by withdrawal bleeding without anesthesia, and definitively diagnosed preoperatively by using hysterofiberscopy.
Adult↗
Spindle cell carcinoma of the pancreas.
We experienced a rare case of spindle cell carcinoma of the pancreas. The patient was a 74-year-old man who complained of abdominal pain and loss of weight. Ultrasonographic scans revealed a hypoechoic solid mass in the head of the pancreas, 4 cm in diameter, with a high echoic spot suggestive of central necrosis or hemorrhage. The mass was hypodense on enhanced computed tomographic scans and hypovascular on angiograms. At laparotomy, the tumor had invaded to the mesocolon, but dissemination and distant metastasis were not found. We therefore performed pylorus-preserving pancreatoduodenectomy and ascending colectomy. The patient was discharged on postoperative day 26 after an uneventful recovery. Two months later, he was readmitted because of ascites, with positivity of spindle cells shown on cytology; he died on day 92 after surgery. In the resected specimen, the tumor had a mostly sarcomatous component, consisting of spindle-shaped cells, and a small glandular component. Immunohistochemically, both components were positive for cytokeratin and epithelial membrane antigen, but negative for vimentin and desmin. The tumor was diagnosed as a spindle cell carcinoma of the pancreas. Perineural invasion, lymphatic permeation, and blood vessel invasion were found, but lymph node metastasis was not found. Although a curative operation was performed, the outcome in this patient was very poor.
Aged↗
Increased serum levels of soluble vascular cell adhesion molecule 1 and E-selectin in patients with localized scleroderma.
BACKGROUND: The serum levels of soluble forms of vascular cell adhesion molecule 1 (sVCAM-1) and E-selectin (sE-selectin) can be used as a marker of endothelial activation. OBJECTIVE: We investigated whether the serum level of sVCAM-1 and sE-selectin in patients with localized scleroderma (LSc) was correlated with the clinical or serologic features of this disease. METHODS: Serum samples from 59 patients with LSc, 20 patients with systemic sclerosis (SSc) and 29 healthy controls were examined using specific enzyme-linked immunosorbent assays. RESULTS: The serum levels of sVCAM-1 and sE-selectin in patients with LSc were significantly higher than those of the healthy controls. The serum levels of sVCAM-1 and sE-selectin were correlated with both the number of sclerotic lesions and the number of involved areas. CONCLUSION: These results indicate that the serum levels of sVCAM-1 and sE-selectin may reflect the extent of the skin involvement (ie, the disease severity) and may be useful for monitoring the in vivo states of endothelial activation in LSc.
Adult↗
Serum levels of tissue inhibitor of metalloproteinases 2 in patients with systemic sclerosis.
BACKGROUND: The serum tissue inhibitor of metalloproteinases 1 (TIMP-1) level was reported to be a useful indicator of disease activity, especially of lung fibrosis in patients with systemic sclerosis. TIMP-2 is also an important inhibitor of matrix metalloproteinases (MMPs), such as interstitial collagenase, gelatinase, and stromelysin, which control the metabolism of the extracellular matrix. However, serum levels of TIMP-2 in patients with systemic sclerosis (SSc) have not been investigated. OBJECTIVE: We sought to determine the clinical significance of serum levels of TIMP-2 and MMP-2 in patients with SSc. METHODS: Serum samples were obtained from 128 patients with SSc (68 with limited cutaneous SSc and 60 with diffuse cutaneous SSc). Twenty-seven serum samples from healthy age- and sex-matched individuals were also examined as controls. The TIMP-2 and MMP-2 levels were determined by means of sandwich enzyme-linked immunosorbent assays. RESULTS: The serum TIMP-2 levels were elevated in 29 (22.7%) of the 128 patients with SSc and were significantly higher than those of the healthy control subjects. The serum TIMP-2 levels were significantly correlated with the extent of skin sclerosis in the patients with SSc. The incidence of decreased percentage of the diffusing capacity of lung for carbon monoxide (DLCO ) and that of an elevated erythrocyte sedimentation rate were significantly greater in the patients with elevated TIMP-2 levels compared with the patients with normal TIMP-2 levels (P <.05). When these patients were classified into 2 groups by disease activity, TIMP-2 levels were significantly more elevated in the high active group than in those low active group (P <.001). The serum MMP-2 levels of the patients with SSc were not significantly higher than those of the healthy control subjects. CONCLUSION: These findings suggest that the serum TIMP-2 level is a useful marker of the extent of skin sclerosis and disease activity in patients with SSc. The balance of TIMP-2 and MMP-2 may play an important role in patients with SSc. Furthermore, TIMP-2 may be thought to contribute to the development of disease in patients with SSc.
Adolescent↗
Characterization of PCB-degrading bacteria immobilized in polyurethane foam.
This study is carried out to investigate (1) conditions for the synthesis of polyurethane foam to be used for immobilizing microorganisms, (2) the viability of microorganisms immobilized simultaneously into the pores of a polyurethane foam when the foam is synthesized, and (3) the difference in the ability to degrade PCBs between the immobilized and suspended microorganisms. The results of this study show that polyurethane foam is suitable for synthesizing 10% NCO-prepolymer, water and surfactant in the ratio of 100:2.6:1.2 (w/w), respectively, and the viability of microorganisms (input microbes) immobilized in the foam is high. The input microbes, designated as strain SY5, are isolated from a municipal sewage treatment plant. In addition, immobilized strain SY5 degrades 5-40% more PCB of a PCB mixture (Aroclor 1242) than the suspended strain SY5.
Journal Article↗
Increased serum levels of soluble vascular cell adhesion molecule-1 and soluble E-selectin in patients with polymyositis/dermatomyositis.
BACKGROUND: Elevated levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble E-selectin (sE-selectin) have previously been reported in patients with various inflammatory diseases, but not in patients with polymyositis/dermatomyositis (PM/DM). OBJECTIVES: To determine serum levels and significance of sVCAM-1 and sE-selectin in patients with PM/DM. PATIENTS AND METHODS: Serum samples from 36 PM/DM patients, 30 patients with systemic sclerosis and 25 healthy control subjects were examined using specific enzyme-linked immunosorbent assay systems. RESULTS: The serum levels of sVCAM-1 in the PM/DM patients were significantly higher than those in the healthy controls. The elevated serum sVCAM-1 levels were correlated with the values of elevated erythrocyte sedimentation rate and elevated serum hyaluronate levels in the PM/DM patients. The serum sE-selectin levels in the PM/DM patients were also significantly higher than those in the healthy controls. The elevated serum sE-selectin levels were correlated with the incidence of elevated creatine kinase activities. The concentrations of serum sE-selectin were correlated with the serum tissue inhibitor of metalloproteinase-1 concentrations in the PM/DM patients (r = 0.53). CONCLUSIONS: These results suggest that serum sVCAM-1 and sE-selectin levels might be useful for detecting disease activity in patients with PM/DM.
Adolescent↗
Characterization of autoantibodies to endothelial cells in systemic sclerosis (SSc): association with pulmonary fibrosis.
To determine the prevalence and the characterization of antibodies to endothelial cells in patients with SSc, serum samples from 80 patients with SSc, 20 patients with systemic lupus erythematosus (SLE), and 20 healthy control subjects were examined by ELISA using cultured human umbilical vein endothelial cells (HUVEC), indirect immunofluorescence analysis (IIF), and immunoblotting using cytoplasmic extract of HUVEC. IgG and/or IgM isotype anti-endothelial cell antibodies (AECA) were demonstrated by ELISA in 43 of 80 patients with SSc (54%), in 15 of 20 patients with SLE (75%), and in none of 20 healthy control subjects. Immunofluorescence analysis on HUVEC substrate showed homogeneous cytoplasmic staining. Immunoblotting demonstrated that these patients had antibodies directed to one or several antigens of approximately 60, 90, 110 and 140 kD, and the most common responses were to the 90-kD antigen. By the immunofluorescence method using HUVEC, affinity-purified anti-90-kD antibodies showed identical cytoplasmic staining to that produced by sera positive for AECA. Furthermore, AECA were closely correlated with pulmonary fibrosis in patients with SSc. These findings suggest that patients with SSc have abnormal antibodies to endothelial cell antigens, and support the hypothesis that endothelial dysfunction is involved in the development of this disease.
Adult↗