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Biomedical subjects

R Suzuki

Publications and source records attributed to R Suzuki.

At least 289 records · Page 16Linked to original sources

Neutral endopeptidase 3.4.24.11 inhibition potentiates the inhibitory effects of type-C natriuretic peptide on leukotriene D4-induced airway changes.

1. Microvascular leakage, a primary feature of inflammation, is well known for worsening the asthmatic condition. Gene expression of and a specific receptor for type-C natriuretic peptide (CNP), initially considered a neuropeptide, have been detected in the human vascular wall and secretion of CNP from vascular endothelial cells has recently been demonstrated. These facts suggest the presence of a vascular natriuretic peptide system and led us to expect that CNP may act beneficially on airway microvascular leakage in asthma. In the present study, we investigated the effects of CNP against leukotriene (LT) D4-induced airway microvascular leakage and bronchoconstriction and how these effects were potentiated by thiorphan, a potent neutral endopeptidase 3.4.24.11 (NEP) inhibitor. 2. Anaesthetized male guinea-pigs, ventilated via a tracheal cannula, were placed into a plethysmograph for 10 min, in order to measure pulmonary mechanics and mean blood pressure, after challenge with 2 micrograms/kg LTD4 and then the extravasation of 20 mg/kg Evans blue dye into airway tissue was investigated to indicate and evaluate microvascular leakage. 3. Intravenous administration of CNP (100, 300 and 1000 micrograms/kg) significantly inhibited the LTD4-induced microvascular leakage and bronchoconstriction in a dose-dependent manner. These inhibitory effects were enhanced by pretreatment with 20 mg/kg thiorphan, suggesting the important role of NEP in the pulmonary metabolism of CNP. 4. We believe that these results are encouraging for the further investigation of the therapeutic applications of exogenous CNP in asthma.

Animals↗

Computed tomographic findings in non-specific interstitial pneumonia/fibrosis.

The entity of non-specific interstitial pneumonia/fibrosis (NIP) has recently been recognized as an addition to the current classification of idiopathic interstitial pneumonia, which includes usual interstitial pneumonia, desquamative interstitial pneumonia, diffuse alveolar damage, and bronchiolitis obliterans organizing pneumonia. We studied the computed tomographic (CT) findings of nine NIP patients who were diagnosed pathologically. The main findings were ground glass opacities (66.7%), airspace consolidation (88.9%) and reticular opacities (89.7%), distributed predominantly in the bilateral and lower lung. In all cases, the clinical and abnormal opacification observed on the chest CT was improved by the administration of corticosteroid. Both the subpleural and patchy distributed opacifications predominantly in the bilateral and lower lung, and the good response to treatment may help to differentiate non-specific interstitial pneumonia from other types of idiopathic interstitial pneumonia.

Adult↗

The regulation of fiber arrangement in advanced cellular cementogenesis of human teeth.

This study observed cellular cementum in fully formed human premolars by light and electron microscopy to elucidate how cementoblasts regulate the fiber arrangement in cementum. Cementoblasts had wing-like processes encircling the principal fibers, where Sharpey's fibers were dense. On the cementum-facing side, wing-like processes were segmented into finger-like processes in parallel with the cementum surface. Observations suggested that with the segmentation intrinsic fibers appeared around principal fibers in close association with finger-like processes. Where Sharpey's fibers were few or absent, where intrinsic fibers were the main fibrous element of the cementum, cementoblasts had only few or no wing-like processes, but had finger-like processes not associated with the wing-like processes on the cementum-facing side. On the basis of the origin of the finger-like processes the main results suggest that there are two kinds of cementoblasts: one has finger-like processes associated with wing-like processes and secretes intrinsic fibers from the finger-like processes to incorporate the principal fibers for tooth support. The second type has finger-like processes not associated with wing-like processes, this type secretes intrinsic fibers from the finger-like processes to adjust the cementum thickness.

Adult↗

Recombinant human bone morphogenetic protein-2 stimulates osteoblast differentiation and suppresses matrix metalloproteinase-1 production in human bone cells isolated from mandibulae.

Bone morphogenetic protein (BMP), a member of the transforming growth factor superfamily, is one of the most potent growth factors that stimulate osteoblast differentiation and bone formation. We investigated the effects of recombinant human BMP-2 (rhBMP-2) on osteoblast differentiation and matrix metalloproteinase-1 (MMP-1) production in human bone cells (HBC) isolated from mandibulae of 3 adult patients. rhBMP-2 at concentrations over 50 ng/ml significantly stimulated alkaline phosphatase activity and parathyroid hormone (PTH)-dependent 3', 5'-cyclic adenosine monophosphate accumulation, which are early markers of osteoblast differentiation, in HBCs. rhBMP-2 (500 ng/ml) also enhanced the level of PTH/PTH related-peptide receptor mRNA expression in HBCs. Although neither HBCs untreated nor treated with rhBMP-2 produced measurable amounts of osteocalcin, which is a marker of more mature osteoblasts, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] induced ostocalcin mRNA expression and its protein synthesis in these cells. rhBMP-2 inhibited 1,25(OH)2D3-induced osteocalcin synthesis in HBCs at both the mRNA and protein level. rhBMP-2 also significantly suppressed MMP-1 production and MMP-1 mRNA expression at concentrations over 500 ng/ml. These results suggest that rhBMP-2 exerts anabolic effects on human osteoblastic cells derived from mandibulae by stimulation of osteoblast differentiation and down-regulation of MMP-1 synthesis.

Adult↗

Establishment and characterization of Japanese encephalitis virus-specific, human CD4(+) T-cell clones: flavivirus cross-reactivity, protein recognition, and cytotoxic activity.

We analyzed the CD4(+) T-lymphocyte responses of two donors who had received Japanese encephalitis virus (JEV) vaccine 6 or 12 months earlier. Bulk culture proliferation assays showed that peripheral blood mononuclear cells (PBMC) responded to JEV antigens (Ag) but also responded at lower levels to West Nile virus (WNV) and dengue virus type 1, 2, and 4 (D1V, D2V, and D4V, respectively) Ag. Five JEV-specific CD4(+) human T-cell clones and one subclone were established from PBMC of these two donors. Two clones responded to WNV Ag as well as to JEV Ag, whereas the others responded only to JEV Ag. Three of five CD4(+) T-cell clones had JEV-specific cytotoxic activity and recognized E protein. The HLA restriction of the JEV-specific T-cell clones was examined. Three clones were HLA-DR4 restricted, one was HLA-DQ3 restricted, and the HLA restriction of one clone was not determined. T-cell receptor analysis showed that these clones expressed different T-cell receptors, suggesting that they originated from different T lymphocytes. These results indicate that JEV vaccine induces JEV-specific and flavivirus-cross-reactive CD4(+) T lymphocytes and that these T lymphocytes recognize E protein. The functions and HLA restriction patterns of these T lymphocytes are, however, heterogeneous.

CD4-Positive T-Lymphocytes↗

Bull's-eye macular dystrophy associated with peripheral involvement.

Although central vision in Stargardt's disease is impaired relatively early, peripheral function is usually little affected and patients do not lose all vision. We report 4 patients with bull's-eye macular dystrophy that is indistinguishable from Stargardt's disease/fundus flavimaculatus, but with very depressed peripheral retinal function. One patient had bull's-eye maculopathy with a dark choroid on the fluorescein angiogram with a normal peripheral fundus and good retinal function initially. Sixteen years later, however, peripheral bone corpuscle pigmentation and optic disc atrophy developed and the electroretinogram became nonrecordable. Three patients from another family also had peripheral pigment degeneration besides macular degeneration. These cases may represent a rare combination of Stargardt's disease and retinitis pigmentosa. However, there was no clinical sign or even suggestion of retinitis pigmentosa at the initial examination in 1 patient. The mode of inheritance in 3 of our patients is probably autosomal recessive.

Child↗

Chronic oral antigen exposure induces lymphocyte migration in anaphylactic mouse intestine.

Persistent diarrhea, vomiting, and dehydration are symptoms often seen in patients suffering from food allergy after chronic antigen exposure; however, the precise mechanisms involved have not been well defined. In an effort to clarify the mechanisms of the chronic intestinal changes attributable to genuine IgE-mediated anaphylactic reactions induced by orally administered antigen, a mouse model was established by s.c. implantation of a murine hybridoma capable of producing monoclonal anti-trinitrophenyl IgE antibody, and the morphologic and immunologic changes occurring in the intestine upon chronic antigen exposure were investigated. In the early stage after ingestion of the antigen, diarrhea and noticeable infiltration of mast cells as well as eosinophils into the lamina propria were observed. A substantial increase in serum histamine levels as well as an increase in leukotriene C4 synthesis in the jejunal mucosa were observed 1 h after antigen challenge. Also, the synthesis of leukotriene B4 was significantly elevated for up to 9 h after antigen challenge. The expression of both intercellular adhesion molecule-1 (ICAM-1) on mucosal vascular endothelial cells and IAd on epithelial cells was markedly enhanced, and noticeable infiltration of eosinophils and lymphocytes was also confirmed in the mouse model after chronic antigen exposure. These findings suggest that oral antigen exposure induces anaphylactic reactions in the intestine mediated by mast cells and eosinophils in response to the IgE-antigen complex in the early phase, and also induces lymphocyte migration after chronic antigen exposure.

Administration, Oral↗

Synthesis of a biologically active fluorescent derivative of GM1, a main Ginseng saponin metabolite formed by intestinal bacteria.

A fluorescent derivative of GM1 [20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol], a main Ginseng saponin metabolite formed by intestinal bacteria, was obtained from the condensation of its trisnor-aldehyde derivative with dansyl hydrazine. The dansylated GM1 fluoresced strongly and showed almost the same properties as its parent compound in lipophilicity and biological activities, so this fluorescent compound might provide an insight into the mechanism of pharmacological activities of GM1.

Antineoplastic Agents↗

Antimalarial activity and nucleoside transport inhibitory activity of the triterpenic constituents of Cimicifuga spp.

The in vitro antimalarial activity against human malaria parasite (Plasmodium falciparum, FCR-3 strain) was examined using 59 triterpenoids obtained during studies on the triterpenic constituents of Cimicifuga spp. The 50% effective concentration values (EC50) of 25 active triterpenoids were 1.0-3.0 microM, and 19 of the compounds had a common 16, 23:23, 26:24, 25-triepoxy group in the side-chain moieties. Among the active triterpenoids, 9 also showed significant inhibition of nucleoside transport in mouse splenocytes. A relationship between the antimalarial activity and the inhibition of nucleoside transport involving these triterpenoids is discussed.

Animals↗

Role of phosphodiesterase 4 isoenzyme in alkaline phosphatase activation by calcitonin in porcine kidney LLC-PK1 cells.

To confirm the intracellular signal transduction in regulation of alkaline phosphatase (ALP) activity by calcitonin in kidney tubular cells, effects of several inhibitors of cyclic nucleotide phosphodiesterase (PDE) isoenzymes and cyclic AMP-dependent protein kinase (PKA) on the action of salmon calcitonin in porcine kidney tubular epithelial cells LLC-PK1 were examined. A confluent culture of LLC-PK1 cells was treated with calcitonin and inhibitors in Dulbecco's modified Eagle's medium supplemented with 0.1% bovine serum albumin, and intracellular cyclic AMP content and ALP activity were measured after incubation for 30 min and 48 hr, respectively. Calcitonin and PDE 4 inhibitors increased cyclic AMP level and ALP activity in the cells, and PDE 4 inhibitors synergistically potentiated the effects of calcitonin. Calcitonin induced ALP activation by treatment for the first 1 hr, as well as continuous treatment for 48 hr, while it never increased the enzyme activity just after 1-hr exposure. Rolipram, an inhibitor of PDE 4 isoenzyme, induced ALP activation by itself and in combination with calcitonin by only a long term treatment (48 hr). The activation of ALP by calcitonin and rolipram each alone and in combination was completely abolished by a PKA inhibitor, H-89. These results confirm that calcitonin induces ALP activation through the cyclic AMP-PKA pathway and that PDE 4 isoenzyme is closely associated with the calcitonin-receptor system and plays a major role in hydrolysis of cyclic AMP produced in the kidney tubular cells.

3',5'-Cyclic-AMP Phosphodiesterases↗

Application of modal analysis to human subjects: comparison of healthy subjects and cleft lip and palate subjects.

To evaluate the vibrational characteristics of the maxillary arch, modal analysis was applied to human subjects. Twelve healthy human subjects and 2 cleft lip and palate (CLP) subjects with surgical failure in their cleft area were chosen for this study. The main measurement system was composed of an impact hammer, acceleration sensor, CF-6400 FFT Analyzer, PC-9821Xn personal computer, and Vibrant PC modal analysis software. The measurement points were established on 12 teeth between the upper first molars on both sides of the mouth in healthy subjects, and on 10 teeth in CLP subjects. In all subjects, one distinct resonance peak was observed in each transfer function at each measurement point. All of the transfer functions of a given subject strongly resembled each other in terms of shape. The amplitude and modal shapes of the maxillary arches of all the subjects were obtained by using a curve-fitting function in the software. In the healthy subjects, the maxillary arch expanded outward and shrank inward on vibration with no node after an impact. In the CLP subjects, the phase lag between the large and small segment was distinctly observed after an impact. In this study, the applicability of modal analysis for human subjects was demonstrated.

Adult↗

QT interval prolongation in the patients receiving maintenance hemodialysis.

QT prolongation is associated with a poor prognosis in patients with various diseases. The pathogenesis of the long QT syndrome is not well understood and little is known about the QT interval in the patients receiving maintenance hemodialysis. We evaluated changes in the QTc interval and investigated factors that contribute to its prolongation in 42 patients receiving maintenance hemodialysis. We also examined the association between the QTc interval and ventricular arrhythmias on 24-h ambulatory electrocardiograms. Comparison of standard 12-lead electrocardiograms of 42 patients and of 30 healthy controls matched for age and sex showed that the QTc interval in the patients was significantly prolonged (432.6 +/- 24.9 vs 402.0 +/- 21.0 ms, p <0.001). Multivariate analysis using stepwise multiple regression identified diabetes mellitus and the ejection fraction measured by echocardiography as independent risk factors for QTc prolongation. The QTc interval was significantly prolonged in patients with complex VPCs (couplets or salvos) (n = 13, 447.9 +/- 14.4 ms) on 24 h ambulatory ECG compared with simple VPCs (none or occasional) (n = 29, 425.6 +/- 25.8 ms) (p = 0.03). In conclusion, the QTc interval was prolonged in patients receiving maintenance hemodialysis and QTc prolongation was associated with complex VPCs. Decreased myocardial contractility and diabetes mellitus contributed to QTc prolongation.

Arrhythmias, Cardiac↗

[Effect of UFT on treatment of urological cancer--effect of UFT on treatment of invasive bladder cancer and advanced prostate cancer. Ibaraki Urological Cancer Chemotherapy Study Group].

A prospective randomized joint study was conducted to evaluate the usefulness of UFT 1) as a postoperative adjuvant therapy in patients with invasive bladder cancer who had undergone curative combination therapy with operation and/or chemotherapy and/or radiation therapy, 2) as an endocrine chemotherapy in patients with newly diagnosed stage C/D prostate cancer, for a period of 3 years from January, 1992. For bladder cancer, of 36 patients with invasive bladder cancer, clinically cured by combination therapy, 20 patients were treated with UFT as an adjuvant chemotherapy over 12 months, and they were compared to 16 patients with no adjuvant therapy. After excluding 10 inappropriate patients, 12 patients in the UFT treatment group and 14 patients with no adjuvant treatment group were observed. For prostate cancer, of 29 patients with clinically stage C/D prostate cancer, 13 were treated with endocrine therapy in combination with UFT, and 16 patients were treated with endocrine therapy alone. After excluding 7 inappropriate patients, 10 patients with endocrine chemotherapy and 12 patients with hormonal therapy were observed. The non-recurrence rate, survival rate and side effects of UFT were evaluated. In the study of bladder cancer, neither a significant difference of non-recurrent rate nor of survival rate was seen between the two groups. In the study of prostate cancer, neither a significant difference of non-recurrent rate nor of survival rate was seen between the two groups. These findings suggest UFT is less useful as an adjuvant therapy for the invasive bladder cancer and as an endocrine chemotherapy for newly diagnosed advanced prostate cancer.

Administration, Oral↗

[Changes in QOL in patients with brain tumors measured by mood changes during and after treatment].

UNLABELLED: Patients with brain tumors are exposed to severe stress which may have an influence on their quality of life (QOL). To measure QOL in those patients, we measure their mood state during and after the treatments. MATERIALS: 16 patients who were admitted to our department for treatment of brain tumors, were included in the study. The tumors included 5 gliomas, 6 meningiomas and others. They were 7 males and 9 females, and age distributed from 19 to 74 years old. All patients presented more than 90% of the Karnofsky performance score (KPS) on discharge, so they were expected to return to their previous social life. METHOD: The self-answering tests were performed on admission (Pre), on discharge (Post 1), and at more than 5 months after the discharge (Post 2). The tests included an original questionnaire asking consent to admission and treatment, and concerning the feeling of disability to cope with conditions of living, Cornell Medical Index (CMI) which measured the neurosis, and Profile of mood state (POMS) which measured the 6 subscales of patients mood states including tension-anxiety (TA), depression (D), anger-hostility (AH), vigor (V), fatigue (F), and confusion (C). RESULTS: The questionnaire showed that the patients feel satisfied with having consented to the treatment. The feeling of disability to cope with living became stronger in Post 2 than in Pre. CMI showed a borderline of neurosis in three patients on admission, and in four patients in Post 2. Only the TA of POMS subscale improved significantly in Post 2. However, other subscales were unchanged. It is characteristic that all of the subscales of POMS showed less disturbance on discharge compared with that on admission, but, they returned to the Prelevel after they returned to social life. CONCLUSIONS: Patients with brain tumors have satisfactory consent to the treatment, however, they feel disability to cope with social life. On discharge, they showed a better mood state compared to that on admission, but the mood state turned for the worse again during the follow-up period. It is evident that patients with brain tumors are exposed to severe stress even after the completion of the treatment. The results necessitate our taking patients' mental health into consideration for our treatment protocol.

Adult↗

Establishment and characterization of melanoma cell line derived from malignant melanoma of human uterine cervix.

A cell line designated HOMM (human Okuno Malignant Melanoma) was established from the uterine cervical malignant melanoma of a 65-year-old Japanese woman. The cell line has grown well and serial passages were successively carried out 32 times within 19 months. The monolayer cultured cells revealed anaplastic and pleomorphic features, and grew in multilayers. They had long cell protrusions and many dark brown pigments. Immunocytochemical stain revealed that S-100 protein existed in the cytoplasm. Electron micrographs also revealed that they had a number of pre-melanosomes and melanosomes in the cytoplasm. All cultured cells were triploid, the modal chromosome number was 68 and the marker chromosomes were presented. The cells were transplanted into an immune-suppressed hamster's cheek pouch and produced a malignant melanoma resembled original tumor.

Aged↗

[Chronic pancreatitis, acute pancreatitis].

MRCP has been recognized as a safe and noninvasive diagnostic method. In the present study we evaluated the usefulness of MRCP in diagnosis of chronic and acute pancreatitis. Two-dimensional fast asymmetric spin-echo (FASE) MRCP was performed in 40 patients with chronic pancreatitis and 13 with acute pancreatitis. In 29 patients (72.5%) with chronic pancreatitis and 9 (66.7%) with acute pancreatitis, main pancreatic duct (MPD) was visualized entirely. MRCP could demonstrate the characteristic findings of chronic pancreatitis such as dilatation and irregularity of MPD in most cases. In acute pancreatitis, MRCP indicated that MPD was normal in diameter, but irregular in configuration compared with that of the control group. MRCP may facilitate the diagnosis of chronic and acute pancreatitis.

Acute Disease↗