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Biomedical subjects

N Suzuki

Publications and source records attributed to N Suzuki.

At least 415 records · Page 23Linked to original sources
PubMed1999

Prolactin locally produced by synovium infiltrating T lymphocytes induces excessive synovial cell functions in patients with rheumatoid arthritis.

OBJECTIVE: To elucidate the role of prolactin (PRL) produced in joints as part of the pathological response of rheumatoid arthritis (RA), we studied PRL production and prolactin receptor (PRLR) expression in RA synovium and its effects on RA synovial cell functions. METHODS: Proinflammatory cytokine and matrix metalloproteinase (MMP) production by RA synovial cells was estimated by ELISA, Western blotting analysis, and zymography. Expression of PRLR by RA synovial cells and local production of PRL were estimated by reverse transcription polymerase chain reaction and immunohistochemical staining. RESULTS: PRL enhanced RA synovial cell proliferation. Production of proinflammatory cytokine and MMP was augmented and production of tissue inhibitor of metalloproteinases (TIMP)-1 was inhibited by PRL treatment of RA synovial cells, suggesting that PRL enhances total collagenase activity in the joints. PRLR was exclusively expressed on fibroblast-like synovial cells and lymphocytes infiltrating into the synovium in patients with RA. Both synovium infiltrating T lymphocytes and, to a lesser extent, fibroblast-like synovial cells synthesized PRL, suggesting that PRL acts as a paracrine as well as autocrine activator of RA synovial cell functions. Stimulation of synovial cells by PRL induced rapid translocation of STAT-5 from cytoplasm into nuclei of RA synovial cells, suggesting that transcriptional regulation of RA synovial cell functions by PRL affects STAT-5. Inhibitors of PRL release, such as bromocriptine, inhibited proliferation of proinflammatory cytokines and collagenases by RA synovial cells. CONCLUSION: Our findings emphasize the importance of PRL, locally produced by infiltrating T lymphocytes, for aberrant synovial cell functions in RA, and suggest possible clinical application of PRL inhibitors.

Aged↗
PubMed1999

[A patient with pulmonary alveolar proteinosis who underwent whole lung lavage under total intravenous anesthesia with propofol].

A 32-year-old male suffering from pulmonary alveolar proteinosis underwent whole lung lavage under one-lung ventilation and total intravenous anesthesia with propofol and fentanyl. The lung lavage was initially performed for the right lung, and for the left lung two weeks later. Spo2 and Pao2 declined at the time of lung degassing and drainage of lavage fluid (minimum values; Spo2 = 83%, Pao2 = 55.9 mmHg), and recovered on filling with the lavage fluid. Although pulmonary arterial pressure and central venous pressure were slightly increased at the time of unilateral lung filling, there was no marked change in arterial pressure, heart rate or cardiac output for lavage of either lung. % VC, DLCO and PaO2 markedly improved after whole lung lavage, from 26.0%, 5.84 ml.min 1.mmHg-1, and 61.9 mmHg in room air to 41.6%, 9.96 ml.min-1.mmHg-1, and 89.3 mmHg in room air, respectively. Since propofol does not inhibit hypoxic pulmonary vasoconstriction and is able to maintain a stable level of anesthesia, it is a useful anesthetic agent for whole lung lavage.

Adult↗
PubMed1999

Synovium infiltrating T cells induce excessive synovial cell function through CD28/B7 pathway in patients with rheumatoid arthritis.

OBJECTIVE: To clarify involvement of synovial T cells in the development of synovial inflammation in patients with rheumatoid arthritis (RA), we analyzed cellular interactions between synovial cells and infiltrating T cells via CD28/B7-1 and B7-2. METHODS: Synovial cells and infiltrating T cells were recovered separately from RA synovial tissues. Expression of CD28, B7-1, and B7-2 of synovial cells was analyzed by immunohistochemical staining and immunofluorescence analysis. Interleukin 1beta (IL-1beta), IL-6, and matrix metalloprotease 3 (MMP-3) secreted by synovial cells in the presence of infiltrating T cells were measured by ELISA. Nuclear transcription factor CD28 responsive complex was detected by a gel shift assay. RESULTS: Both CD28+ T cells and B7-1/B7-2+ cells were found accumulating in the mononuclear cell infiltrate of RA synovial tissues and B7-1/B7-2+ cells were mainly LeuM3+ synovial cells. CD28 responsive complex was detected in nuclear extracts of freshly isolated lymphocytes from RA synovial tissues, but not those from osteoarthritis synovial tissues or normal peripheral blood, suggesting in vivo activation of T cells by the CD28/B7-1/B7-2 interactions. The irradiated autologous synovium infiltrating T cells notably enhanced IL-1beta, IL-6, and MMP-3 production by the synovial cells. The enhancement of proinflammatory cytokine and MMP-3 production by the synovial cells co-cultured with the T cells was abolished by the addition of CTLA4-Ig, anti-B7-1, and anti-B7-2 monoclonal antibodies. CONCLUSION: These results suggest that cellular interactions between synovium infiltrating T lymphocytes and synovial cells via B7/CD28 pathways are intimately associated with development and exacerbation of inflammation in RA synovial cells.

Adult↗
PubMed1999

[Electroconductive lithotripsy: clinical results of the Sonolith sigma].

The electroconductive lithotripter (ECL) is a new concept for shockwave generation in which a highly conductive solution channels the discharge between the anode and cathode. Out of 152 patients treated, complete follow up data were available on 151 patients. The average number of shocks per treatment was 2,138. At 3 months the overall stone-free rate was 73.5%. Success rate, defined as stone-free or asymptomatic residual fragments measuring 4 mm or less, was 84.9% for renal and 94.9% for ureteral calculi. The overall success rate for all calculi was 89%.

Adult↗
PubMed1999

[Postoperative hoarseness and sore throat after tracheal intubation: effect of a low intracuff pressure of endotracheal tube and the usefulness of cuff pressure indicator].

Many clinical reports have described postoperative hoarseness and sore throat after general anesthesia. In most cases, these symptoms were attributed to high pressure of the endotracheal tube cuff. The recommended cuff pressure is less than 25 mmHg, as excessive pressure produces ischemia of the tracheal mucosa. However, within the safe pressure range, postoperative hoarseness and sore throat are still often observed. In this study, one hundred and ninety patients of ASA classes I or II were allocated randomly to two groups, low cuff pressure group (< 15 mmHg) or high cuff pressure group (15-25 mmHg), using continuous monitoring with a cuff pressure gauge. We investigated the incidence of postoperative hoarseness and sore throat at 24 hours after intubation and on the seventh postoperative day. The incidence of postoperative hoarseness and sore throat was significantly decreased in the low pressure group at 24 hours after intubation as compared with the high pressure group, but there was no significant difference between the two groups on the seventh postoperative day. These results suggest that keeping the cuff pressure under 15 mmHg can prevent postoperative hoarseness or sore throat at 24 hours after intubation, and that a cuff pressure gauge is thought to be one of the indispensable monitors during anesthesia.

Adult↗
PubMed1999

[Is Palmaz-Schatz stenting effective for second restenosis?].

The long-term outcome after coronary stent placement in restenotic lesions after balloon angioplasty (percutaneous transluminal coronary angioplasty: PTCA)may be less favorable compared to stent treatment of de novo lesions, but the role of stents in restenotic lesions after 2 prior PTCA procedures is unknown. Elective Palmaz-Schatz stent placement was performed in 124 consecutive patients. Stents were placed in 70 patients(56%) in the native coronary arteries for de novo lesions(de novo group), in 33 patients (27%)for restenotic lesions after one prior PTCA(restenosis group), and 21 patients(17%)for restenotic lesions after 2 prior PTCA(second restenosis group). The 3 groups were well matched with respect to lesion type, lesion length, and reference diameter. Stent size was similar in the 3 groups. Follow-up angiograms taken about 6 months after stenting were available for all patients. The restenosis rate after stenting was similar for the de novo group and restenosis group(19% vs 27%, NS). The second restenosis group tended to have a higher restenosis rate after stenting than the de novo group(38% vs 19%, p = 0.06). The frequency of diffuse type in-stent restenosis of the second restenosis group tended to be higher than that of the de novo group(63% vs 13%, p = 0.08). Our results suggest that the restenosis rate after stenting was higher in patients with repeated restenosis. Therefore, other therapeutic methods should be considered.

Angioplasty, Balloon, Coronary↗
PubMed1999

[Apneic anesthesia for microsurgery of the larynx under propofol anesthesia].

Apneic anesthesia with intermittent ventilation (AAIV) under inhalational anesthesia has been reported to improve visualization of the larynx with lack of vocal cord motion in laryngeal microsurgery. In this study, we evaluated AAIV using total intravenous anesthesia with propofol and fentanyl instead of inhalational anesthesia in 11 patients undergoing microsurgery of the larynx, and examined the effects of AAIV on respiration and circulation. Anesthesia was maintained with infusion of propofol 4-10 mg.kg-1.h-1 and intermittent administration of fentanyl and vecuronium intravenously. The lungs were ventilated with 100% oxygen, and the endotracheal tube was removed during the apneic period. AAIV provided the otorhinolaryngologist sufficient room in which to operate and an immobile field without complications in any of the patients. The number of periods of apnea (mean +/- SD) was 3.3 +/- 1.3, and the duration of apnea was 292 +/- 23 seconds. Neither blood pressure nor heart rate changed during the apneic periods. Arterial oxygen saturation measured using pulse oxymetry (Spo2) changed in none of the patients except an obese patient whose Spo2 declined to 90%. End-tidal carbon dioxide level increased for 14.9 mmHg immediately after apneic periods. Propofol vielded stable and adequate levels of anesthesia during apneic periods. We conclude that AAIV using constant monitoring of Spo2 is a useful and safe technique, and that propofol is a suitable anesthetic agent for AAIV.

Anesthesia, Intravenous↗
PubMed1999

[Body surface ultrasonography-guided bronchofiberscopy].

Transbronchial lung biopsies and cytologic studies under ultrasonographic guidance from the body surface were conducted in 39 patients whose lesions were adjacent to the thoracic wall. In 26 patients, biopsy, curettage, or brushing forceps were visualized in the mass or infiltrative lesion by thoracic echogram. Positive findings were obtained in 23 patients, for a conclusive diagnostic rate of 88.5%. Of the 13 patients in whom forceps could not be visualized by echogram, 10 had positive findings, for a diagnostic rate of 76.9%. For visualization by thoracic echogram, abnormal lung lesions must be in direct contact with the thoracic wall. Occasionally, diagnostic procedures may be impeded by anatomical structures such as shoulder joints or scapula. Despite these disadvantages, the ultrasonography-guided bronchofiberscope is quite useful because it facilitates real-time confirmation of the positioning of the forceps relative to the lesions. It is also useful in cases when the peripheral lesions are too small or vague to be demonstrated by fluoroscopy alone, because the echo probe can be the target of the forceps instead of the missing shadows. The diagnostic rate should be higher when the forceps are visualized in the lesions ultrasonographically.

Adult↗
PubMed1999

Response differentiation to facial expression of emotion as increasing exposure duration.

This study investigated whether the underlying structure of responses to facial expressions of emotion would emerge when the exposure time was increased. 25 participants judged facial photographs presented for varying durations of exposure, ranging from 4 msec. to 64 msec. in 4-msec. steps. A dual scaling method was carried out to analyze possible response differentiation as a function of exposure time. Two major components were extracted. Based on the configuration of variables they were interpreted as valence (hedonic tone) and activation. Results indicated that a positive emotion and a highly activated emotion such as surprise and fear were easily recognized under a relatively brief exposure to the stimuli.

Emotions↗
PubMed1999

In vivo analysis of two striated muscle actin promoters reveals combinations of multiple regulatory modules required for skeletal and cardiac muscle-specific gene expression.

We isolated two striated muscle actin genes from medaka Oryzias latipes. OIMA1 is a skeletal muscle actin gene expressed in somitic muscle and head muscle and OIMA2 is probably a cardiac muscle actin gene expressed in both somitic and cardiac muscle. The differential transcription mechanisms for these two genes were examined in embryos by introducing fusion genes in which the OIMA1 or OIMA2 upstream region was connected to the green fluorescent protein gene. Embryos were injected with these fusion genes at the 2-cell stage. A fusion gene containing the region up to -949 of OIMA1 exhibited strong expression in somitic muscle. The coexistence of two regions, -949/-662 and -421/-201, is necessary for skeletal muscle-specific expression of OIMA1. Two E boxes and other unidentified sequences cooperatively function to achieve the full activity of the enhancer -949/-662. As for OIMA2, the region up to -520 is sufficient for strong muscle-specific expression. The region between -520 and -174 of OIMA2 is necessary for specific expression in both skeletal and cardiac muscles. In addition to the CArG box located at -140, an E-box at -430 is important for the expression in cardiac muscle as well as skeletal muscle. When the enhancers for the two muscle actin genes were switched and combined with each other's promoter, they were able to upregulate tissue-specific expression according to their origin. These results suggest that distinct expression patterns of OIMA land OIMA2 are regulated by combination of regulatory modules, each of which contains multiple regulatory elements.

Actins↗
PubMed1999

[A case of stage IV (A3) cervical and upper thoracic esophageal adenocarcinoma successfully treated with concurrent chemoradiotherapy].

We report a case of cervical and upper thoracic esophageal adenocarcinoma with tracheal stenosis and bilateral recurrent nerve palsy. A 64-year-old man with unresectable esophageal cancer (A3, N1, M0) was treated with concurrent chemoradiotherapy. A dose of 67.4 Gy was irradiated to the cervical and upper thoracic area where the primary tumor and lymph node metastases were located, and six courses of 5-FU (250 mg/24 h/day 1-5) and CDDP (5 mg/1 h, just before radiation/day 1-5) were delivered concurrently. The esophageal tumor showed a complete response (CR), and the paratracheal lymph node metastases showed partial responses (PR). The reason these therapies were more effective against the tumor than the lymph node metastases is uncertain. The patient is no longer required to stay in the hospital, and his QOL has been improving. His condition has been maintained for 4 months, so this type of concurrent chemoradiotherapy may be recommended for cervical and upper thoracic esophageal adenocarcinoma.

Adenocarcinoma↗
PubMed1999

Effects of actarit on synovial cell functions in patients with rheumatoid arthritis.

OBJECTIVE: Actarit (4-acetylaminophenylacetic acid), developed in Japan, has been shown to be effective for suppressing disease activity of rheumatoid arthritis (RA). We analyzed effects of actarit on synovial cell functions in patients with RA for insight into the clinical application of this medication. METHODS: RA primary synovial cells were co-cultured with actarit at 10(-4)-10(-7) M. Their subsequent proliferative responses and proinflammatory cytokine and matrix metalloproteinase (MMP) production at the mRNA and protein levels were measured. Effects of actarit on adhesion molecule expression were analyzed by immunofluorescence flow cytometry and cell-cell binding assay. RESULTS: Spontaneous tumor necrosis factor-alpha and interleukin 1beta secretion by primary synovial cells of patients with RA was reduced by actarit at therapeutic concentrations (10(-5)-10(-6) M). In contrast, actarit also suppressed MMP-1 production by the primary synovial cells. In addition, actarit down-regulates CD44 and intercellular adhesion molecule 1 expression on fibroblast-like synovial cell lines, and very late antigen 4 expression on CD14+ macrophage-like synovial cells resulted in the inhibition of lymphocyte adhesion to RA synovial cells. CONCLUSION: The results suggest that actarit acts on RA synovial cells to reduce cell-cell interactions with autologous synovium infiltrating lymphocytes and to inhibit proinflammatory cytokine and MMP production, leading to amelioration of symptoms of RA.

Antirheumatic Agents↗
PubMed1999

Epidermal growth factor protects rat epithelial cells against acid-induced damage through the activation of Na+/H+ exchangers.

We examined the effect of epidermal growth factor (EGF) on acid-induced cell damage in rat gastric epithelial cells (RGM1) and investigated the mechanisms of this effect. Cells were incubated with EGF for 5, 15, 30, and 60 min, and then immersed in an acidified medium (pH 4.0) for 30 min to induce cell damage. EGF prevented cell damage in a concentration- and time-dependent manner. EGF reduced the effects of the acidified medium on the cells, preventing the reduction of intracellular pH. Replacement of Na+ with K+ in the acidified medium canceled the effect of EGF. Indomethacin and W-7 (a Ca-calmodulin inhibitor) did not alter the protective effect of EGF. In contrast, genistein (a tyrosine kinase inhibitor), amiloride (a Na+/H+ exchangers I and II inhibitor), and wortmannin (a phosphatidylinositol 3-kinase inhibitor) significantly decreased the effect of EGF. Expression of Na+/H+ exchangers type I and type II was confirmed by reverse transcription-polymerase chain reaction. Our results demonstrate that EGF prevents acid-induced cell damage, most likely through the activation of a Na+/H+ exchanger II via phosphatidylinositol 3-kinase.

Animals↗
PubMed1998

Farnesyltransferase inhibitors induce cytochrome c release and caspase 3 activation preferentially in transformed cells.

Farnesyltransferase inhibitors (FTIs) represent a new class of anticancer drugs that show promise in blocking the growth of tumors. Here, we report that FTIs are capable of inducing apoptosis of transformed but not untransformed cells. Treatment of v-K-ras-transformed normal rat kidney (KNRK) cells with FTIs leads to the induction of apoptotic cell morphology, chromatin condensation and DNA fragmentation. In addition, fluorescence-activated cell sorter analysis of FTI-treated KNRK cells shows a sub-G1 apoptotic peak (chromosome content of <2 N). This FTI-induced apoptosis is evident only when the cells are grown in low serum conditions (0.1% fetal calf serum) and is observed selectively with transformed KNRK cells and not with untransformed NRK cells. Further analysis of the mechanism underlying this apoptosis has shown that FTI treatment of KNRK cells results in the activation of caspase 3 but not caspase 1. Moreover, the addition of Z-DEVD-fmk, an agent that interferes with caspase 3 activity, can inhibit FTI-induced apoptosis in a dose-dependent manner. Introduction of the CASP-3 gene into MCF7 cells, which lack caspase 3 activity, results in a significant increase of FTI-induced apoptosis. Furthermore, FTI induces the release of cytochrome c into the cytosol. This release is an important feature of caspase 3-mediated apoptosis. These results suggest that FTIs induce apoptosis through the release of cytochrome c from the mitochondria resulting in caspase 3 activation.

Alkyl and Aryl Transferases↗
PubMed1998

Search for genes responsible for UV susceptibility of human cells: involvement of syndecan-1 in UV resistance.

UVr-1 UV-resistant cells were established from UV-sensitive human RSa cells. We looked for genes expressed differentially between UVr-1 and RSa cells using PCR-based mRNA differential display to elucidate the molecular mechanisms underlying UV resistance. The transcription levels of syndecan-1 mRNA were increased in UVr-1 cells compared with those of RSa cells. Syndecan-1 is a transmembrane heparan sulfate proteoglycan and associates with cell adhesion and the cytoskeleton. Flow cytometric analysis using anti-syndecan-1 monoclonal antibody revealed that syndecan-1 was more abundant in UVr-1 cells than in RSa cells. The MTT method revealed that UVr-1 cells treated with the antibody showed higher sensitivity to UV cell killing than mock-treated cells. Studies using antisense oligonucleotides for syndecan-1 showed that antisense-treated UVr-1 cells became sensitive to UV cell killing. Thus, syndecan-1 might be involved in UV resistance in UVr-1 cells.

Antibodies, Monoclonal↗