Biomedical subjects

J Su

Publications and source records attributed to J Su.

At least 19 recordsLinked to original sources

PubMed2006

Two new iridoids from roots of Patrinia scabra Bunge.

Two new iridoids 1,3-dimethyloxy-7-hydroxymethyl-4-(3-methyl-butyryloxymethyl)-1-hydrocyclopenta-4,7-diene[c]pyran-6-one (1) and 1,3-dimethyloxy-7-hydroxymethyl-4-methyloxymethyl-1-hydrocyclopenta-4,7-diene[c]pyran-6-one (2) were isolated from the roots of Patrinia scabra Bunge. The structure elucidation of the isolated compounds was based primarily on HRESIMS, EIMS, IR, UV, 1D- and 2D-NMR analyses, including COSY, HMQC, HMBC and NOESY correlations, as well as X-ray crystallographic analysis.

Crystallography, X-Ray↗

PubMed2003

Pre-neutralization of C5a-mediated effects by the monoclonal antibody 137-26 reacting with the C5a moiety of native C5 without preventing C5 cleavage.

Complement C5a is aetiologically linked to inflammatory tissue damage in conditions like septicaemia, immune complex diseases and ischaemia-reperfusion injury. We here describe a monoclonal antibody (mAb), 137-26, that binds to the C5a moiety of human C5 and neutralizes the effects of C5a without interfering with C5 cleavage and the subsequent formation of lytic C5b-9 complex. Mouse anti-human C5 mAbs were generated and the reactivity with C5 and C5a was detected by ELISA and surface plasmon resonance. The inhibition of C5a binding to C5a receptor was studied using a radioligand binding assay. The effects of the antibody on C5a functions were examined using isolated neutrophils and a novel human whole blood model of inflammation. Haemolytic assays were used to study the effect on complement-mediated lysis. mAb 137-26 reacted with both solid- and solution-phase C5 and C5a in a dose-dependent manner with high affinity. The antibody competed C5a binding to C5a receptor and inhibited C5a-mediated chemotaxis of neutrophils. Furthermore, the antibody effectively abrogated complement-dependent E. coli-induced CD11b up-regulation and oxidative burst in neutrophils of human whole blood. mAb 137-26 was more potent than a C5a receptor antagonist and a previously described anti-C5a antibody. mAb 137-26 did not inhibit complement-mediated lysis, nor did it activate complement itself. Together, mAb 137-26 binds both the C5a moiety of native C5 and free C5a, thereby effectively neutralizing the biological effects of C5a. The antibody may have therapeutic potential in inflammatory diseases where C5a inhibition combined with an operative lytic pathway of C5b-9 is particularly desired.

Animals↗

PubMed2002

Characterization of poly((N-trimethylammonium) ethyl methacrylate)-based gene delivery systems.

We have synthesized a hydrophilic cationic homopolymer of N-trimethylammonium ethyl methacrylate chloride (pTMAEM) and its copolymers with 1-vinyl-2-pyrrolidone (VP) and methyl methacrylate (MMA) at various monomer ratios and examined the physicochemical and biological characteristics of polymer/DNA complexes. All the (co)polymers were able to condense DNA to small particles and protect it from nuclease degradation. The particle size of pTMAEM/DNA complexes was smaller (550-175 nm) than the other polymers (1200-300 nm) tested. The zeta potential of the complexes was increased with increasing (co)polymer/DNA weight ratios and reached the constant value. The plateau value slightly decreased from +28 mV to +21 mV (P > 0.05) when the monomer content was increased. The optimal transfection efficiency of pTMAEM/DNA (655 mU/mg protein) was found at 0.5 polymer/DNA weight ratio and was reduced with increasing weight ratios due to increased cytotoxicity. The maximum transfection efficiency of copolymer/DNA was observed at a weight ratio of one and transfection efficiency slightly decreased with increasing monomer content in the copolymers. Overall, pTMAEM-VP/DNA complexes showed reduced cytotoxicity and increased transfection efficiency as compared with the other (co)polymers tested.

Animals↗

PubMed2002

A gene therapy for cancer based on the angiogenesis inhibitor, vasostatin.

The growth and persistence of solid tumors and their metastasis are angiogenesis-dependent. Vasostatin, the N-terminal domain of calreticulin inclusive of amino acids 1-180, is a potent angiogenesis inhibitor. To investigate whether intramuscular administration of vasostatin gene has the antitumor activity in mouse tumor models, we constructed a plasmid DNA encoding vasostatin and a control vector. Production and secretion of vasostatin protein by COS cells transfected with the plasmid DNA encoding vasostatin (pSecTag2B-vaso) were confirmed by Western blot analysis and ELISA. Conditioned medium from vasostatin-transfected COS cells apparently inhibited human umbilical vein endothelial cell (HUVEC) and mouse endothelial cell (SVEC4-10) proliferation, compared with conditioned medium from the COS cells transfected with control vector or non-transfected cells. Treatment with pSecTag2B-vaso twice weekly for 4 weeks resulted in the inhibition of tumor growth and the prolongation of the survival of tumor-bearing mice. The sustained high level of vasostatin protein in serum could be identified in ELISA. Angiogenesis was apparently inhibited in tumor by immunohistochemical analysis. Angiogenesis was also inhibited in the chicken embryo CAM assay and mouse corneal micropocket assay. The increased apoptotic cells were found within the tumor tissues from the mice treated with plasmid DNA encoding vasostatin. Taken together, the data in the present study indicate that the cancer gene therapy by the intramuscular delivery of plasmid DNA encoding vasostatin, is effective in the inhibition of the systemic angiogenesis and tumor growth in murine models. The present findings also provide further evidence of the anti-tumor effects of the vasostatin, and may be of importance for the further exploration of the application of this molecule in the treatment of cancer.

Angiogenesis Inhibitors↗

PubMed2002

Primary resistance to antibiotics and its clinical impact on the efficacy of Helicobacter pylori lansoprazole-based triple therapies.

AIM: To evaluate Helicobacter pylori primary resistance and its clinical impact on the efficacy of two lansoprazole-based eradication triple therapies. METHODS: H. pylori-positive patients (n=228) were randomized to receive one of the 1-week regimens: lansoprazole 30 mg, clarithromycin 500 mg and amoxicillin 1 g (LAC), or lansoprazole 30 mg, clarithromycin 500 mg and metronidazole 500 mg (LMC), each given twice daily. H. pylori status was assessed by 13C-urea breath test and culture at diagnosis and by 13C-urea breath test 6 weeks after therapy. Antibiotic susceptibility was determined by E-test (n=98). RESULTS: The eradication rates with per protocol/ intention-to-treat analyses were: LAC (n=95/114) 83%/69% and LMC (n=96/114) 85%/72%. Primary resistance was 11% for clarithromycin, 41% for metronidazole and 0% for amoxicillin. Eradication in metronidazole-susceptible/-resistant strains was 85%/82% in LAC and 83%/63% in LMC. Significantly lower cure rates were observed in clarithromycin-resistant patients treated with LAC (95% vs. 0%, P < 0.001) and LMC (86% vs. 0%, P < 0.001). CONCLUSIONS: One-week LAC and LMC are similarly effective therapies. Clarithromycin resistance significantly affected H. pylori eradication in both regimens.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2001

Activation of p38, ERK1/2 and NIK pathways is required for IL-1beta and TNF-alpha-induced chemokine expression in human retinal pigment epithelial cells.

Chemokine secretion by human retinal pigment epithelium (hRPE) in response to IL-1beta and TNF-alpha occurs in infectious and noninfectious retinal diseases. In this study, the roles of p38 kinase and extracellular signal-regulated kinase (ERK) signaling pathways were investigated for IL-1beta- or TNF-alpha-induced IL-8 and MCP-1 secretion by hRPE cells. Treatment of hRPE cells with IL-1beta or TNF-alpha caused increased steady-state IL-8 and MCP-1 mRNA levels and protein secretion. Stimulation of hRPE with IL-1beta and TNF-alpha resulted in degradation of IkappaB-alpha, nuclear translocation of NF-kappaB, and prominent increases in p38 and ERK1/2 phosphorylation for as little as 3 min. The induced IL-8 and MCP-1 mRNA and proteins were partially suppressed by U0126, a specific MEK inhibitor, and by SB202190, a selective p38 inhibitor. This induction was completely blocked by simultaneous administration of the two drugs or by incubation with inhibitors for activation of NF-kappaB such as BAY11-7085, CAPE, and parthenolide. These results suggest that co-activation of MEK/ERK and p38 pathways as well as activation of NIK pathway are essential for IL-1beta- and TNF-alpha-stimulation of IL-8 and MCP-1 gene expression in hRPE cells. Furthermore, co-administration of U0126 and SB202190 did not affect the induced degradation of IkappaB-alpha and NF-kappaB nuclear translocation, indicating that NF-kappaB is activated by IL-1beta and TNF-alpha independently of activation of MEK/MAPK and p38 pathways in hRPE cells.

Blotting, Western↗

PubMed2001

[Permeability of the round window membrane for prednisolone-21-hydrogen succinate. Prednisolone content of the perilymph after local administration vs. systemic injection].

BACKGROUND AND OBJECTIVE: Prednisolone is the drug of first choice for the treatment of cochleovestibular disorders, such as sudden hearing loss. Because of the known side effects, the efficient drug levels to be achieved within inner ear fluids are limited by intravenous administration. The aim of the study was to determine the concentration in the perilymph of prednisolone-21-hydrogen succinate applied into the round window niche in comparison to the concentration after intraperitoneal application. METHODS: Application of prednisolone-21-hydrogen succinate (5 mg in 0.1 ml) on the round window membrane was performed after sedation under microscopic view directly into the round window niche of the guinea pig. In order to compare the results, perilymph samples after systemic application of 60 mg/kg body weight prednisolone were used. The time between application and taking specimens of perilymph from the cochlea varied. Specimens of perilymph were obtained after 15, 20, 80, 180, 330, and 960 min (10 specimens in each group, n = 60) by dissecting the cochlea and opening the apex cochleae. Levels of prednisolone-21-hydrogen succinate in perilymph were measured by isocratic high-pressure liquid chromatography (HPLC). RESULTS: The highest levels of prednisolone-21-hydrogen succinate were found after 180 min: 952.3 mg/l (95% confidence interval: 382.7). After 960 min the level was 18.72 mg/l (95% confidence interval: 16.9). In the group with systemic application, the levels measured were below 14.71 mg/l (95% confidence interval: 7.05). CONCLUSION: The results demonstrate that high levels of prednisolone-21-hydrogen succinate in perilymph are achievable by local application of a single dose into the round window niche. After application of 5 mg, the levels of prednisolone are measurable up to 16 h.

Administration, Topical↗

PubMed2001

The expression and regulation of depolarization-activated K+ channels in the insulin-secreting cell line INS-1.

The aim of the present study was to characterize depolarization-activated outward currents in insulin-secreting INS-1 cells and to investigate the role of K+ channels other than the KATP channels in the regulation of insulin release. Outward currents were inhibited by 4-aminopyridine (4-AP, 10 mmol/l), tetraethylammonium (TEA, 10 mmol/l) and tetrapentylammonium (TPeA, 100 mumol/l) by 55.1 +/- 3.8% (n = 3), 78.1 +/- 3.2% (n = 6) and 98.7 +/- 0.8% (n = 5), respectively. Margatoxin (5 nmol/l) and charybdotoxin (3 mumol/l) had no effect. 4-AP inhibited mainly a fast-activating, slowly inactivating current, whereas the TEA- and TPeA-sensitive current components were slowly activating and non-inactivating. Forskolin and the forskolin analogue 1,9-dideoxyforskolin, which does not stimulate adenylyl cyclase, also inhibited the outward current, suggesting a direct effect on the channels. Using reverse transcriptase polymerase chain reaction (RT/PCR). Kv channel mRNAs of Kv1.4, Kv1.5, Kv2.1, Kv2.2, Kv3.1 and Kv3.2 were detected whereas other Kv channels, Kv1.1, Kv1.2, Kv1.3, Kv1.6 and Kv3.4 were not detected. Insulin secretion in the presence of tolbutamide (100 mumol/l) was increased by 4-AP, TEA and TPeA by 65%, 41% and 150%, respectively. Basal secretion was not affected by these blockers. Our study reveals that the opening of voltage-dependent K+ channels negatively controls insulin secretion in depolarized cells, probably by shortening the action potential thus reducing Ca2+ influx.

1-Methyl-3-isobutylxanthine↗

PubMed2001

Synthesis of polyhydroxysterols (I): synthesis of 24-methylenecholest-4-en-3beta,6beta-diol, a cytotoxic natural hydroxylated sterol.

Starting from stigmasterol (2), 24-methylenecholest-4-en-3beta, 6beta-diol (1), a cytotoxic natural dihydroxylated sterol, was synthesized via 10 steps in 20% overall yield. The introduction of a side-chain of sterol was achieved by solid-liquid phase-transfer Wittig reaction using (3-methyl-2-oxo)butyltriphenylarsonium bromide (12) and K(2)CO(3). Construction of the steroidal nucleus was finished by the addition of 3beta-acetoxycholest-5,6-en-24-one (7) with NBA in dioxane under ambient temperature and by the elimination of 3beta, 6beta-diacetoxy-5a-bromocholestane-24-one (9). The spectral data of the synthetic product (1) are completely consistent with those of the natural compound (1).

Antineoplastic Agents↗

PubMed2001

Adenovirus-mediated interferon-beta gene therapy suppresses growth and metastasis of human prostate cancer in nude mice.

The purpose of this study was to determine the effects of interferon-beta (IFN-beta) gene transfer on the growth of PC3MM2 human prostate cancer cells in nude mice. Intralesional delivery of an adenoviral vector encoding murine IFN-beta (AdIFN-beta), but not a vector encoding bacterial beta-galactosidase (AdLacZ), suppressed PC3MM2 tumors in a dose-dependent manner. At the highest dose (2x10(9) plaque-forming units, PFU), a single injection of AdIFN-beta (but not AdLacZ) suppressed orthotopic PC3MM2 tumors and development of metastasis by 80%, and eradicated the tumors in 20% of mice. Immunohistochemical staining showed that AdIFN-beta-treated tumors contained fewer microvessels, fewer proliferating cells, and more apoptotic cells than did the control tumors. Compared with controls, tumors injected with AdIFN-beta expressed higher levels of IFN-beta and inducible nitric oxide synthase (iNOS) and lower levels of basic fibroblast growth factor (bFGF) and transforming growth factor beta1 (TGF-beta1). In vitro analysis indicated that expression of bFGF and TGF-beta1 in PC3MM2 cells could be suppressed by the nitric oxide donor sodium nitroprusside. These data suggest that intratumoral delivery of the IFN-beta gene with adenoviral vectors could be an effective therapy for prostate cancer and that tumor suppression by AdIFN-beta correlated with up-regulation of iNOS and down-regulation of angiogenesis.

Adenoviridae↗

PubMed2001

Automated reticulocyte counting using the Sysmex RAM-1.

Reticulocyte counting using the Sysmex RAM-1 was evaluated. The results of 113 samples analysed on the Sysmex RAM-1 were compared with those from both flow cytometry (FCM) and a manual technique. Reticulocyte counting with the Sysmex RAM-1 showed excellent precision, with an overall coefficient of variance (CV) less than 5%, and almost no carry-over. Reticulocyte counts were stable after blood storage for 48 h at 4 degrees C and room temperature (RT). Linearity was demonstrated very well for Sysmex RAM-1 and FCM (rRAM=0.9998, rFCM=0.9974, P < 0.001) when reticulocyte counts were 5 x 109/l-480 x 109/l. Comparisons of methods showed a good relation for reticulocyte counts between Sysmex RAM-1 and manual counting (r=0.9760), FCM and manual counting (r=0.9623), and Sysmex RAM-1 and FCM (r=0.9527). Analysis of receiver operating characteristic curves showed that the true-positive rate (TPR) was 0.95 for Sysmex RAM-1, and 0.83 for FCM; the area under curve was 0.999 and 0.972 for Sysmex RAM-1, 0.990 and 0.900 for FCM. These findings confirm that Sysmex RAM-1 can make counting reticulocytes easier, more accurate and more reproducible.

Humans↗

PubMed2001

Laboratory evaluation of the Sysmex SE-9500 automated haematology analyser.

The Sysmex SE-9c500 is a new, fully automated haematology analyser, providing a complete blood count (CBC), including a five-part differential count (DC), with flagging of morphological abnormalities. The SE-9500 was evaluated according to guidelines published by the International Committee for Standardisation in Haematology (ICSH). The results demonstrated minimal carryover (< 0.01%) and excellent linearity for WBC, RBC, HGB and platelet (PLT) (r > 0.995). Samples were stable with regard to CBC parameters after storage for up to 48 h at room temperature (RT) and 4 degrees C. Imprecision was generally acceptable for all CBC parameters (CV < 5%). Correlation between the SE-9500 and reference methods was excellent (r > 0.97) for all the major CBC parameters (WBC, RBC, HGB, PLT). There was minimal interference for WBC, RBC, HGB and PLT at high concentrations of bilirubin (BIL=224 micromol/l) or triglyceride (TG=7.78 mmol/l). SE-9500 reference values for CBC parameters are presented. Our results indicate that the SE-9500 is an excellent tool for routine haematological examination.

Adult↗

PubMed2001

Functional relevance of human adh polymorphism.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were C. J. Peter Eriksson and Tatsushige Fukunaga. The presentations were (1) 4-Methylpyrazole as a tool in the investigation of the role of ADH in the actions of alcohol in humans, by Taisto Sarkola and C. J. Peter Eriksson; (2) ADH2 polymorphism and flushing in Asian populations, by Wei J. Chen, C. C. Chen, J. M. Ju, and Andrew T. A. Cheng; (3) Role of ADH3 genotypes in the acute effects of alcohol in a Finnish population, by Hidetaka Yamamoto, Kathrin Kohlenberg-Müller, and C. J. Peter Eriksson; (4) Clinical characteristics and disease course of alcoholics with different ADH2 genotypes, by Mitsuru Kimura, Masanobu Murayama, Sachio Matsushita, Haruo Kashima, and Susumu Higuchi; (5) ADH2 polymorphism, alcohol drinking, and birth defects, by Lucinda Carr, D. Viljoen, L. Brooke, T. Stewart, T. Foroud, J. Su, and Ting-Kai Li; and (6) ADH genotypes and alcohol use in Europeans, by John B. Whitfield.

Adult↗

PubMed2001

Evidence for a locus on chromosome 1 that influences vulnerability to alcoholism and affective disorder.

OBJECTIVE: Depression (major depression or depressive syndrome) is more prevalent in alcoholic than in nonalcoholic subjects in families with multiple members with alcoholism studied as part of the Collaborative Study on the Genetics of Alcoholism (National Institute on Alcohol Abuse and Alcoholism). First-degree relatives of probands with comorbid alcoholism and depression have a higher prevalence of both disorders than relatives of probands with alcoholism alone, and both groups have a higher prevalence than the relatives of comparison subjects selected without regard to psychopathology. Data from the collaborative study were used to test three phenotypes (comorbid alcoholism and depression, alcoholism or depression, and depression) for genetic linkage. METHOD: Genome-wide sibling-pair linkage analyses were performed with the phenotypes comorbid alcoholism and depression, alcoholism or depression, and depression (major depression or depressive syndrome). Analyses were performed in two data sets (initial and replication data sets) from subject groups ascertained with identical criteria, as well as in the combined data set. RESULTS: Peak lod scores on chromosome 1 (near 120 centimorgan) for the alcoholism or depression phenotype were 5.12, 1.52, and 4.66 in the initial, replication, and combined data sets, respectively. The corresponding lod scores on chromosome 2 were 2.79, 0.20, and 3.26; on chromosome 6, they were 3.39, 0.00, and 0.92; and on chromosome 16, they were 3.13, 0.00, and 2.06. Lod scores on chromosome 2 for the comorbid alcoholism and depression phenotype in the three data sets were 0.00, 4.12, and 2.16, respectively. CONCLUSIONS: The results suggest that a gene or genes on chromosome 1 may predispose some individuals to alcoholism and others to depression (which may be alcohol induced). Loci on other chromosomes may also be of interest.

Adult↗

PubMed2001

Nasal chondromesenchymal hamartoma in children: report of 2 cases with review of the literature.

Hamartoma in the nasal cavity of children is especially rare. Most documented cases occurred in infants, with characteristic histologic features of a mixture of various mesenchymal tissues. McDermott et al designated it nasal chondromesenchymal hamartoma in 1998, and it has since been considered a distinct clinicopathological entity. We report 2 such examples in a full-term male newborn and a 9-month-old boy, respectively. Histologically, both cases were characterized by a mixture of various mesenchymal elements, including spindle cells, collagen fibers, and irregular islands of osseous and chondroid tissue. Immunohistochemical study showed positivity to vimentin and S100 protein. Ultrastructural examination of case 1 demonstrated fibroblastic and myofibroblastic differentiation in tumor cells. There were 11 cases of nasal chondromesenchymal hamartoma in children published to date. The tumor has a benign biological behavior, and complete resection is the treatment of choice. It is apt to be misdiagnosed because of overlapping histologic features shared with a number of benign and malignant soft tissue tumors. Awareness of this entity is essential for correct diagnosis and adequate therapy.

Actin Cytoskeleton↗

PubMed2001

Hepatocellular carcinoma and aflatoxin exposure in Zhuqing Village, Fusui County, People's Republic of China.

Hepatocellular carcinoma (HCC) is a common cause of cancer morbidity and mortality in Asia and Africa. Epidemiological studies have found that dietary exposure to aflatoxin B1 (AFB1) and chronic infection with hepatitis B virus are two major risk factors for HCC. We have collated the incidence and mortality data of malignant tumors from 1973 to 1999 in Zhuqing Village, Fusui County, an area with very high HCC rates, and found that this cancer accounted for 64% of the total cancer incidence. Dietary intake of AFB1 was monitored for 1 week in a study group consisting of 15 males and 14 females from different households in this village. Four of 29 participants (13.8%) and 3 of 15 (20%) male participants were hepatitis B virus surface antigen positive. AFB1 was detectable in 76.7% (23 of 30) of ground corn samples (range, 0.4-128.1 ppb), 66.7% (20 of 30) of cooking peanut oil samples (range, 0.1-52.5 ppb), and 23.3% (7 of 30) of rice samples (range, 0.3-2.0 ppb) collected from each household. Mean levels of serum AFB1-albumin adducts in this group were 1.24 +/- 0.31 pmol/mg of albumin at the beginning of the study and 1.21 +/- 0.19 pmol/mg of albumin at the end of the period. Urinary AFB1 metabolites were detectable in 88.9% (24 of 27) samples (range, 0.9-3569.7 ng/24-h urine). These data provide the exposure and disease risk information for establishing intervention studies to diminish the impact of aflatoxin exposure in this high-risk population.

Adult↗

PubMed2001

Clinical utility of frozen section in sentinel node biopsy in breast cancer.

One hundred sixty-five breast cancer patients underwent a sentinel lymph node biopsy procedure over a period of 2 years. Sentinel node (SN) could be successfully localized in 157 (95%) of the patients. Complete axillary lymph node dissection was performed only if the frozen section (FS) revealed a positive SN. All SN specimens were further evaluated by hematoxylin and eosin on multiple sections and cytokeratin immunohistochemisty. The patients whose SNs were negative by FS but positive by permanent histopathologic evaluation underwent a delayed axillary lymph node dissection. SN was positive in 41 of 157 (26%) patients. Eighteen (44%) of the 41 patients with SN metastases were diagnosed intraoperatively by FS and underwent a one-stage definitive surgical treatment. The benefit of FS was most notable in patients with T1c and larger lesions.

Adult↗

PubMed2001

Study on action of acupuncture on ventromedial nucleus of hypothalamus in obese rats.

Effects of acupuncture on the spontaneous discharge of nerve cells and levels of monoamine neurotransmitters in ventromedial nucleus of hypothalamus (VMH) of the obese rats were investigated. Results indicated that the levels of tyrosine (Tyr) and dopamine (DA) were lowered, the levels of 5-hydroxytryptamine (5-HT) and 5-hydoxyindole acetic acid (5-HIAA) increased, and the frequency of the spontaneous discharge of nerve cells in VMH lowered in the obese rat group as compared with the normal group. When acupuncture obtained the effect of weight reduction, the frequency of spontaneous discharges of nerve cells in VMH were markedly increased, and the levels of Tyr, DA and tryptamine (Typ) and 5-HT/5-HIAA ratio elevated, and the 5-HT level lowered. It is suggested that the virtuous regulative action of acupuncture on VMH might be one of the key factors in acupuncture for weight reduction.

Acupuncture↗