Biomedical subjects

C S Park

Publications and source records attributed to C S Park.

At least 19 recordsLinked to original sources

PubMed1999

Identification and characterization of a putative C. elegans potassium channel gene (Ce-slo-2) distantly related to Ca(2+)-activated K(+) channels.

Two putative homologues of large conductance Ca(2+)-activated K(+) channel alpha-subunit gene (slowpoke or slo) were revealed by C. elegans genome sequencing. One of the two genes, F08B12.3 (Ce-slo-2), shows a relatively low amino acid sequence similarity to other Slo sequences and lacks key functional motifs, which are important for calcium and voltage sensing. However, its overall structure and regions of homology, which are conserved in all Slo proteins, suggest that Ce-SLO-2 should belong to the Slo channel family. We have cloned a full-length cDNA of the Ce-slo-2, which encodes a protein containing six putative transmembrane segments with a K(+)-selective pore and a large C-terminal cytosolic domain. Green fluorescent protein (GFP) and whole-mount immunostaining analyses revealed that Ce-slo-2 is specifically expressed in neuronal cells at the nerve ring, at the ventral nerve cord of the mid-body, and at the tail region. We have also identified a putative human counterpart of Ce-slo-2 from a human brain EST database, which shows a stretch of highly conserved amino acid residues. Northern blot and mRNA dot blot analyses revealed a strong and specific expression in brain and skeletal muscle. Taken together, our data suggest that Ce-slo-2 may constitute an evolutionarily conserved gene encoding a potassium channel that has specific functions in neuronal cells.

Amino Acid Sequence↗

PubMed1999

Copulsation balloon for right ventricular assistance: preliminary trials.

BACKGROUND: Options for management of acute right ventricular (RV) failure are limited. This report describes preliminary testing of a temporary RV assist device that acts by direct compression of the RV. The system comprises a pancake-shaped silicone balloon (5 cm diameter) connected to a drive console that delivers a 65-mL pneumatic pulse during cardiac systole. METHODS AND RESULTS: Initial in vivo tests were performed on 6 pigs (weight, 41+/-4 kg). RV wall motion and stroke volume were monitored via transesophageal echocardiography. Acute RV failure was created by graded right coronary ligation, which yielded a 63% reduction in RV stroke volume (39.9+/-8.2 to 14.7+/-1.9 mL; P<0.002). We secured the balloon over the RV free wall by attaching it to the edges of the opened pericardium. The sternum was then reapproximated, and data were collected with the device off and on (every beat). Device placement had no deleterious effect on RV function. Balloon activation returned RV stroke volumes to normal (37.8+/-9.2 mL) and increased mean pulmonary artery pressures from 13+/-2 to 16+/-3 mm Hg (P<0.01). RV compression did not induce or exacerbate tricuspid regurgitation. Mean aortic pressure improved from postinfarction levels but did not return to normal. CONCLUSIONS: We conclude that the pulmonary circulation can be supported in the short term via cardiac compression and that balloon copulsation techniques for short-term RV failure should be tested in long-term models.

Angioplasty, Balloon↗

PubMed1999

Decreased formation of ethoxyacetic acid from ethylene glycol monoethyl ether and reduced atrophy of testes in male rats upon combined administration with toluene and xylene.

Male painters are commonly exposed to ethylene glycol monoethyl ether (EGE), a well known reproductive toxic agent causing testicular atrophy, in the form of solvent mixture containing toluene (TOL) and xylene (XYL). This study was carried out to determine the effect of exposing male rats to solvent mixture containing TOL and XYL on the EGE (200 mg/kg) on testicular atrophy and production of toxic metabolite, ethoxyacetic acid (EAA) from EGE. Compared to the extent of testes atrophy observed upon EGE administration alone, the combined administration of EGE (200 mg/kg) with TOL (250 mg/kg) and XYL (500 mg/kg) for 4 weeks has reduced the extent of testes atrophy by 25%. The combined administration delayed the time for appearance of the highest plasma concentration (t(max)) of EAA from 3 to 6 h and also decreased the highest concentration (Cmax) as well as the total amount of plasma EAA (AUC(0-18 h)) by 45 and 29%, respectively. This explained the diminished testicular atrophy in male rats observed when EGE was administered in a solvent mixture containing TOL and XYL. This study suggested that testicular toxicity observed in male painters caused by EGE may be decreased when they are exposed to EGE in the form of solvent mixture containing TOL and XYL.

Acetates↗

PubMed1999

Human papillomavirus may be common within nasopharyngeal carcinoma of Caucasian Americans: investigation of Epstein-Barr virus and human papillomavirus in eastern and western nasopharyngeal carcinoma using ligation-dependent polymerase chain reaction.

BACKGROUND: Nasopharyngeal carcinoma (NPC), particularly those tumors endemic to the Far East, commonly harbor Epstein-Barr virus (EBV), thought to serve as an important oncogenic promoter. Human papillomavirus (HPV) is associated with a proportion of upper aerodigestive tract carcinomas. We hypothesized that HPV might also contribute to the pathogenesis of NPC, and we queried whether geographic and racial distinctions may be identified between NPC of the Far East versus those diagnosed in Caucasian American patients with regard to the interrelationship of histologic subtype and viral infection. MATERIALS AND METHODS: Formalin-fixed paraffin-embedded tissue (FFPET) from 30 patients (6 Caucasian Americans, 1 Chinese American, 14 and 9 patients from Korea and China, respectively) were studied using the ligation-dependent polymerase chain reaction (LD-PCR). These cases were histologically classified according to the World Health Organization (WHO) schema for NPC. Consensus target probes complementary to the L1 region of over 30 HPV types, as well as target probes complementary to EBER-1 (EBV-related nontranslated latency-associated RNA), were used to amplify target sequences. RESULTS: Seven of 30 NPC (23%) contained HPV sequences. There were 6 Caucasian American patients with NPC; 3 cases (50%) were HPV positive (HPV+). Two of these Caucasian Americans had WHO type I tumors: one was HPV+ and EBV negative (EBV-) and the other was HPV-/EBV+. The remaining Caucasian American NPCs were WHO-II/III tumors which tested as follows: two were coinfected with HPV and EBV, the other two contained EBER but not HPV sequences. The single Oriental American patient had a WHO-III NPC which was HPV-/EBV+. Of the Eastern NPC patients, 4 (1 WHO-I, 3 WHO-II/III) of 23 (17%) NPCs contained HPV sequences as well as EBV. Conclusion. Human papillomavirus appears to be uncommonly (17%) associated with NPC in patients from the Far East and was detected more often (50%) in NPC from American Caucasian patients. Some of these tumors conformed to our perceptions and expectations of NPC (eg, WHO-I tumors being EBV-/HPV+ and WHO-III tumors being EBV+/HPV-), but other tumors did not conform to these expectations (eg, WHO-III NPC occasionally harboring both HPV and EBV). There appears to be a broad profile in the relationship between HPV, EBV, and NPC histologic subtype. Unfortunately, the number of American Caucasian cases studied are too small to allow for strong conclusions.

Asian People↗

PubMed1999

Preventive effects of the heparin-coated stent on restenosis in the porcine model.

The coronary stent reduces acute coronary arterial occlusion and late restenosis during and after coronary intervention. However, stent thrombosis and restenosis are still major limitations in the widespread use of the coronary stent. Local drug delivery using the heparin-coated stent may be a new approach, which reduces the incidence of stent thrombosis and restenosis. In order to evaluate the effects of the heparin-coated stent on stent restenosis, heparin-coated stents were compared with control stents in a porcine coronary stent restenosis model. Stent overdilation injury (stent:artery = 1.3:1.0) was performed with bare Wiktor stents (group I, n = 10) and heparin-coated Wiktor stents (group II, n = 20; HEPAMED, Medtronics) in porcine coronary arteries. Follow-up quantitative coronary angiography (QCA) was performed at 4 weeks after stenting, and histo-pathologic assessments of stented porcine coronary arteries were compared in both groups. On QCA, percent diameter stenosis was significantly higher in group I than in group II (16.3% +/- 6.62% vs. 9.6% +/- 5.06%, P < 0.05). The injury score of stented porcine coronary arteries was the same in both groups (1. 26 +/- 0.23 vs. 1.20 +/- 0.22). The area of pathologic stenosis of the stented arteries was higher in group I than in group II (41.6% +/- 12.5% vs. 27.1% +/- 9.9%, P < 0.005). The neointimal area was higher in group I than in group II (4.58 +/- 1.41 mm(2) vs. 2.57 +/- 1.07 mm(2), P < 0.05). By immunohistochemistry, the proliferating cell nuclear antigen (PCNA) index was higher in group I compared with group II (11.2% +/- 6.75% vs. 6.3% +/- 4.14%, P < 0.05). The heparin-coated stent is effective in the prevention of late coronary stent restenosis in a porcine coronary stent restenosis model. This may be related to the inhibition of neointimal cell proliferation.

Animals↗

PubMed1999

An immunohistochemical analysis of heat shock protein 70, p53, and estrogen receptor status in carcinoma of the uterine cervix.

OBJECTIVES: It has been shown that heat shock proteins (HSPs) protect cells from death caused by various noxious stimuli. Overexpression of HSP70 seems to be related to hormonal regulation of cell proliferation and/or down-regulation of sex steroid receptors. Wild-type p53 has been reported to repress HSP70 gene expression. It has been shown that mutant p53-HSP70 complex is highly expressed in cancer. However, the relationship between HSPs and steroid receptors or tumor suppressor gene products has not been well understood in uterine cervical carcinoma. This study was undertaken to examine the expression of HSP70, estrogen receptor (ER), and p53 in carcinoma of the uterine cervix. In addition, we analyzed HPV infection status and compared it to such immunohistochemical parameters. We also analyzed the relationship between these biological products and their clinicopathologic characteristics. METHODS: Paraffin-embedded tissue sections were obtained from 84 patients with carcinoma of the uterine cervix. Expression of HSP70, p53, and ER was evaluated by immunohistochemical staining using anti-HSP70 monoclonal antibody (SPA810), anti-p53 (BP53.12), and ER1D5 antibody, respectively. PCR HPV detection was done by dot hybridization method. RESULTS: Positive staining of HSP70 was detected in 73% of the cases. HSP70 positivity was significantly higher in stage I cervical cancer than in stages II-IV (P = 0.02). This was associated with neither tumor size, lymph node status, parametrial involvement status, nor tumor markers (TA-4). Furthermore, there was no significant correlation between HSP70 positivity and the expression of p53 or ER or HPV infection status. CONCLUSION: These data suggested that HSP70 positivity was frequent in uterine cervical cancer, especially in the early stages. However, this was not significantly correlated with clinicopathologic characteristics nor with the expression of p53 or ER nor with HPV infection in carcinoma of the uterine cervix.

Female↗

PubMed1999

Chronic administration of the non-peptide CRH type 1 receptor antagonist antalarmin does not blunt hypothalamic-pituitary-adrenal axis responses to acute immobilization stress.

Antalarmin is a pyrrolopyrimidine compound that antagonizes corticotropin-releasing hormone (CRH) type 1 receptors (CRHR1). In order to assess the effects of antalarmin treatment on hypothalamic-pituitary-adrenal (HPA) function we measured the plasma concentrations of adrenocorticotropic hormone (ACTH) and corticosterone in animals treated with either antalarmin or vehicle for 1 week or for 8 weeks. We found that antalarmin treatment for 1 week did not affect basal concentrations of ACTH or corticosterone. In contrast, treatment for 8 weeks significantly lowered basal ACTH and corticosterone concentrations and also significantly decreased the basal corticosterone to ACTH ratio, indicating decreased basal adrenocortical responsiveness to ACTH. However, immobilization stress resulted in ACTH and corticosterone concentrations that were the same in animals treated with vehicle or antalarmin for either 1 or 8 weeks. We conclude that even though 8-week antagonism of CRHR1 by the non-peptide antalarmin blunts basal concentrations of ACTH and corticosterone, and affects the adrenal responsiveness to ACTH, it does not blunt the HPA response to acute stress, and it does not appear to cause stress-induced adrenal insufficiency.

Adrenocorticotropic Hormone↗

PubMed1999

Transglycosylation of naringin by Bacillus stearothermophilusMaltogenic amylase to give glycosylated naringin.

Naringin, a bitter compound in citrus fruits, was transglycosylated by Bacillus stearothermophilus maltogenic amylase reaction with maltotriose to give a series of mono-, di-, and triglycosylnaringins. Glycosylation products of naringin were observed by TLC and HPLC. The major glycosylation product was purified by using a Sephadex LH-20 column. The sturcture was determined by using MALDI-TOF MS, methylation analysis, and (1)H and (13)C NMR. The major transglycosylation product was maltosylnaringin, in which the maltose unit was attached by an alpha-1-->6 glycosidic linkage to the D-glucose moiety of naringin. This product was 250 times more soluble in water and 10 times less bitter than naringin.

Antioxidants↗

PubMed1999

Nitric oxide metabolites in induced sputum: a marker of airway inflammation in asthmatic subjects.

BACKGROUND AND OBJECTIVE: The role of nitric oxide (NO) needs to be further clarified in allergic inflammation. This study was designed to investigate the relationships between NO metabolites and eosinophil count, eosinophil cationic protein (ECP), interleukin (IL)-5 in induced sputum from asthmatics. METHODS: Hypertonic saline-induced sputum was obtained in 25 asthmatic subjects, among which 13 patients were examined before and after anti-asthmatic medications including steroid preparations. Ten normal subjects were enrolled as controls. Fresh expectorated sputum separated from saliva was treated with equal volume of dithiothreitol 0.1%, cytospinned for cell count, and the supernatant was collected for biochemical assay. NO metabolites were assayed by using modified Griess reaction. ECP was measured by fluoroimmunoassay, and detected IL-5 by a sandwich ELISA. RESULTS: Asthmatic subjects, compared with controls, had significantly higher concentration of NO metabolites (1035.4 +/- 125.3 vs 557.2 +/- 101.5 micromol/L, P < 0.01), higher percentage of eosinophils (25.6 +/- 4.6 vs 1.7 +/- 0.2%, P < 0.01), and higher levels of ECP (1117.8 +/- 213.9 vs 154.6 +/- 47.4 microg/L, P < 0.01) in the induced sputum. IL-5 was detected more frequently in asthmatic subjects than in control subjects (11/25 [44%] vs 1/10 [10%], P < 0.05). According to asthma severity, moderate to severe asthmatic subjects (n = 18) had higher level of NO metabolites (1143.8 +/- 156.3 vs 575.5 +/- 89.5 micromol/L, P < 0. 01), higher levels of ECP and IL-5 (P < 0.01, respectively) in the induced sputum than in those of mild asthmatic subjects (n = 7). NO metabolites, the percentage of eosinophils, the levels of ECP, and IL-5 were reduced following treatment with anti-asthmatic drugs (P < 0.01, respectively). There were significant positive correlations between NO metabolites and percentage of eosinophils or ECP (r = 0. 34, P < 0.05; r = 0.28, P < 0.05). Negative correlations were noted between FEV1, FEV1/FVC and proportion of eosinophils, ECP, or IL-5 levels. CONCLUSION: These findings confirmed that the level of NO metabolites was increased in the tracheobronchial secretion of asthmatic subjects and was paralleled with severity of asthma. Measurement of NO metabolites in induced sputum may be used for monitoring the degree of airway inflammation in asthmatics.

Adolescent↗

PubMed1999

Association of Epstein-Barr virus infection with p53 protein accumulation but not bcl-2 protein in nasopharyngeal carcinoma.

AIMS: The aim of this study was to investigate the association of Epstein-Barr virus (EBV) infection with status of p53 protein expression in nasopharyngeal carcinoma (NPC). The expression of EBV gene and gene product, p53 protein and bcl-2 protein in NPC was histopathologically studied. METHODS AND RESULTS: In-situ hybridization using oligonucleotide probe to EBV-encoded small RNAs (EBERs) and immunohistochemistry using monoclonal antibodies against EBV latent membrane protein 1 (LMP1), p53 protein and bcl-2 proteins were performed in 56 primary NPCs. EBERs were detected in 46 (82%) cases and LMP1 in 17 (30%) cases. While 30 of 32 (94%) cases in differentiated nonkeratinizing carcinoma (NKC, WHO type 2) and 16 of 17 (94%) cases in undifferentiated carcinoma (UC, WHO type 3) showed EBERs expression, neither five cases of keratinizing squamous cell carcinoma (KSCC, WHO type 1) nor two cases of adenocarcinoma showed EBERs. bcl-2 protein was detected in 50 (89%) cases, but its expression did not depend on expression of LMP1. p53 protein was detected in 31 (55%) cases, and there was a correlation between expression of EBERs and p53 protein (P < 0.05) but not between LMP1 and p53 protein. CONCLUSION: In this study, close association of NKC and UC but not KSCC with the latent infection with EBV was demonstrated. The induction of bcl-2 protein by LMP1, as shown in vitro, was not demonstrated. The association between overexpression of p53 protein and the presence of EBV suggests that some EBV-encoded protein, which may be different from LMP1, may play a role for nuclear accumulation of p53 protein.

Epstein-Barr Virus Infections↗

PubMed1999

Production and characterization of monoclonal antibodies against human airway mucins.

The objective of this study was to generate and characterize monoclonal antibodies (MAbs) against human airway mucins, and therefore, should serve as a useful tool in studying the regulation of airway mucins in various physiological or pathological situations of human airway. As an antigen, we used a high molecular mass mucin preparation purified from the sputum of normal human subjects. Two monoclonal hybridomas, namely MAbs HM02 and HM03 were obtained and they showed strong immunoreactivity against purified or crude mucin in sputum or bronchial washing of normal human subject. With the high immunoreactivity of these MAbs, mucin contents could be analyzed with more than 100-fold dilution of human airway secretion. The antibodies recognized carbohydrate epitopes because their immunoreactivity was completely abolished by treatment of the mucin with 5 mM periodate. Further characterization of MAbs HM02 and HM03 showed that: (1) they belong to the IgM type; (2) they bind to high molecular mass mucins based on Western blot; (3) they could indirectly immunoprecipitate human airway mucin and as we know, this is the first to demonstrate immunoprecipitation of human airway mucin with anti-human mucin antibodies; and (4) they bind to the goblet cell in airway epithelium as well as some submucosal glands based on immunohistochemistry. Therefore, MAbs HM02 and HM03 should be able to serve as an invaluable tool in studying the regulation of airway mucins in various physiological and pathological situations of human airway.

Animals↗

PubMed1999

Association of a tetraspanin CD9 with CD5 on the T cell surface: role of particular transmembrane domains in the association.

CD9 is a member of the tetraspanin superfamily which is characterized by four transmembrane (TM) domains and associates with other surface molecules. This tetraspanin was recently found to be expressed on mature T cells. Here, we investigated which molecules associate with CD9 on T cells and which CD9 domains are required for the association. Immunoprecipitation of T cell lysates with anti-CD9 mAb followed by immunoblotting with mAb against various T cell molecules showed the association of CD9 with CD3, CD4, CD5, CD2, CD29 and CD44. Because association with CD5 was most prominent, we determined the role of CD9 TM or extracellular (EC) domains in the association with CD5. CD9 mutant genes lacking each domain were constructed and introduced into EL4 thymoma cells deficient in CD9 but expressing CD5. Among various types of stable EL4 transfectants, EL4 transfected with the mutant gene lacking TM domains (TM2/TM3) between two EC domains expressed a small amount of the relevant protein without showing association with CD5. CD9(-)CD5(-) monkey COS-7 cells transfected with this mutant gene and the CD5 gene expressed both transfected gene products, but the association of these was not detected. EL4 cells transfected with a CD9/CD81 chimera gene (the CD9 gene containing TM2/TM3 of CD81) expressed the chimeric protein on the cell surface and showed association with CD5. These results suggest an essential role of particular CD9 TM domains in the surface expression of the CD9 molecule as well as the association with CD5.

Animals↗

PubMed1999

Nutritionally-directed compensatory growth enhances mammary development and lactation potential in rats.

A nutritionally-regulated compensatory growth regimen imposed during a growing period from prepuberty to gestation can significantly affect mammary development and subsequent lactation performance. The objectives of this study were as follows: 1) to determine whether a compensatory nutrition regimen enhances lactation potential for the first and second lactation cycles and 2) to determine the extent to which a compensatory nutrition regimen modulates cell proliferation, differentiation, and apoptosis and expression of genes in mammary tissues of female rats. Female Sprague-Dawley rats (n = 122, 35 d of age) were randomly assigned either to the control group, with free access to diet, or to a stair-step compensatory nutrition feeding regimen, with an alternating 2-2-3-3-wk schedule. The regimen began with an energy-restricted diet (40% restriction) for 2 wk, followed by the control diet for 2 wk; this step was then repeated at 3-wk intervals. Pups of dams from the compensatory nutrition regimen group gained more during mid-lactation than did control group pups. Mammary tissues were obtained from early (d 2) and late (d 19) lactating rats. Mammary tissue from the compensatory nutrition group exhibited increased cell proliferation and greater gamma-glutamyltranspeptidase and ornithine decarboxylase gene expressions than did tissue from the control group during early lactation of both cycles. Mammary tissue from the compensatory nutrition group also had fewer apoptotic cells than tissue from the control group during late lactation of the first lactation cycle. These results suggest that the compensatory nutrition regimen imposed during the peripubertal developmental phase stimulated mammary growth and enhanced lactation performance by affecting the expression of genes that regulate the cell cycle.

Adaptation, Physiological↗

PubMed1999

Rational type of laparoscopic hysterectomy and safety in anesthetic profiles.

OBJECTIVE: To evaluate what type of surgery would be more reasonable among 3 types of laparoscopic hysterectomy and to evaluate the safety of cardio-pulmonary changes on these patients during these operations. METHOD: A retrospective study was carried out in 215 women who underwent laparoscopic hysterectomy including laparoscopic-assisted vaginal hysterectomy (LAVH), laparoscopic hysterectomy (LH), total laparoscopic hysterectomy (TLH). Blood gas analysis, end-tidal CO2 levels and vital signs were checked and compared with control and preceding values. RESULTS: The average duration of operation was 102.5 min, 83.8 min and 118.3 min for LAVH (n = 97), LH (n = 75) and TLH (n = 43), respectively (p < 0.05). The average amount of bleeding was 297.5 ml, 152.3 ml and 149.2 ml for each type of hysterectomy, respectively. Hemoglobin decreased by an average of 1.6 g/100 ml, 0.9 g/100 ml and 0.8 g/100 ml, respectively. There was a lesser amount of bleeding for LH and TLH than for LAVH (p < 0.05). Profiles of blood gas analysis and expiratory CO2 varied significantly according to the operative stages under controlled anesthesia (p < 0.05), but were within the normal range. CONCLUSION: These results demonstrate that laparoscopic procedures advancing below the uterine vasculature can be considered effective for hysterectomies and that proper anesthesia can safely control the cardio-pulmonary changes during laparoscopic hysterectomy.

Adult↗

PubMed1999

Suppression of flavin-containing monooxygenase by overproduced nitric oxide in rat liver.

Effects of excessive nitric oxide (NO) produced in vivo by an i.p. injection of bacterial lipopolysaccharide (LPS) on hepatic microsomal drug oxidation catalyzed by flavin-containing monooxygenase (FMO) were determined. At 6 and 24 h after the LPS injection, liver microsomes were isolated and FMO activities were determined by using FMO substrates like thiobenzamide, trimethylamine, N,N-dimethylaniline, and imipramine. Liver microsomal FMO activities of LPS-treated rats were decreased significantly for all these substrates. Microsomal content of FMO1 (the major form in rat liver) in LPS-treated rats as determined by immunoblotting, was severely decreased as well. In support of this, hepatic content of FMO1 mRNA was decreased by 43.6 to 67.3%. However, the hepatic content of inducible NO synthase (iNOS) mRNA was increased by 2.6- to 5.4-fold and the plasma nitrite/nitrate concentration was increased by about 30-fold in the LPS-treated rats. When this overproduction of NO in the LPS-treated rats was inhibited in vivo by a single or repeat doses of either a general NOS inhibitor N(G)-nitro-L-arginine or a specific iNOS inhibitor aminoguanidine, the FMO1 mRNA levels were not severely depressed (70-85% of the control level). Attendant with the reduction of plasma nitrite/nitrate concentration by single and repeated doses of NOS inhibitors, activity and content of FMO1 in liver microsomes isolated from these NOS inhibitor cotreated rats were restored partially (in single-dose inhibitors) or completely (in repeat doses). In contrast to these NO-mediated in vivo suppressive effects on the mRNA and enzyme contents of FMO1 as well as the FMO activity, the NO generated in vitro from sodium nitroprusside did not inhibit the FMO activities present in microsomes of rat and rabbit liver as well as those present in rabbit kidney and lung. Combined, the excessive NO produced in vivo (caused by the LPS-dependent induction of iNOS) suppresses the FMO1 mRNA and enzyme contents as well as the FMO activities without any direct in vitro effect on the activities of premade FMO enzyme. These findings suggest that NO is an important mediator involved in the suppression of FMO1 activity in vivo. Thus, together with the previously reported suppression on the cytochrome P-450 activities, the overproduced NO in the liver caused by induction of iNOS under conditions of endotoxemia or sepsis suppresses FMO and appears to be responsible for the decreased drug oxidation function observed generally under conditions of systemic bacterial or viral infections.

Animals↗

PubMed1999

Beta-blockade improves adjacent regional sympathetic innervation during postinfarction remodeling.

The effect of beta-blockade on left ventricular (LV) remodeling, when added to angiotensin-converting enzyme inhibition (ACEI) after anterior myocardial infarction (MI), is incompletely understood. On day 2 after coronary ligation-induced anteroapical infarction, 17 sheep were randomized to ramipril (ACEI, n = 8) or ramipril and metoprolol (ACEI-beta, n = 9). Magnetic resonance imaging was performed before and 8 wk after MI to measure changes in LV end-diastolic, end-systolic, and stroke volume indexes, LV mass index, ejection fraction (EF), and regional percent intramyocardial circumferential shortening. (123)I-labeled m-iodobenzylguanidine (MIBG) and fluorescent microspheres before and after adenosine were infused before death at 8 wk post-MI for quantitation of sympathetic innervation, blood flow, and blood flow reserve in adjacent and remote noninfarcted regions. Infarct size, regional blood flow, blood flow reserve, and the increase in LV mass and LV end-diastolic and end-systolic volume indexes were similar between groups. However, EF fell less over the 8-wk study period in the ACEI-beta group (-13 +/- 11 vs. -22 +/- 4% in ACEI, P < 0.05). The ratio of adjacent to remote region (123)I-MIBG uptake was greater in ACEI-beta animals than in the ACEI group (0.93 +/- 0.06 vs. 0.86 +/- 0.07, P < 0.04). When added to ACE inhibition after transmural anteroapical MI, beta-blockade improves EF and adjacent regional sympathetic innervation but does not alter LV size.

Adrenergic beta-Antagonists↗

PubMed1999

Interleukin (IL)-5 downregulates tumor necrosis factor (TNF)-induced eotaxin messenger RNA (mRNA) expression in eosinophils. Induction of eotaxin mRNA by TNF and IL-5 in eosinophils.

An eotaxin is a chemoattractant specific for eosinophils that are known to play a role in helminth infection and allergic responses. Although several cellular sources have been reported to produce eotaxin, it would be interesting to know whether eosinophils are able to produce their own eotaxin and participate in recruitment of themselves in response to inflammation. To this end, a cloned eotaxin complementary DNA was transcribed in vitro to use as a probe for detecting eotaxin messenger RNA (mRNA), and eotaxin protein levels were determined by enzyme-linked immunosorbent assay. Eotaxin mRNA was, as analyzed by in situ hybridization, rarely detectable in unstimulated eosinophils, but was strongly induced in eosinophils when stimulated with tumor necrosis factor (TNF). Interleukin (IL)-5, which is known to be a major factor of eosinophil survival in vivo and in vitro, was also able to induce a modest level of eotaxin mRNA but inhibited TNF-induced eotaxin mRNA expression in a dose-response manner. Dexamethasone inhibited TNF-induced eotaxin mRNA expression. This result was consistent with that from reverse transcription/polymerase chain reaction followed by Southern blot analysis. Unlike the little expression of eotaxin mRNA in the absence of stimuli, the measurement of eotaxin protein revealed that a considerable amount of eotaxin protein was constitutively produced in unstimulated eosinophils. Its expression was upregulated by TNF and IL-5 as well. However, the inhibitory effect of IL-5 on TNF-mediated eotaxin protein production was not as pronounced as that on eotaxin mRNA induction. Collectively, these data reflect the complex physiology of eosinophils in the expression of eotaxin gene upon the exposure to their survival and/or death factors.

Chemokine CCL11↗

PubMed1999

Rapid and easy detection of Helicobacter pylori by in situ hybridization.

Various in situ hybridization (ISH) methods have been used to identify Helicobacter pylori, a causative organism responsible for chronic gastritis and peptic ulcer disease, but they were hard to perform and time consuming. To detect H. pylori in a rapid and easily reproducible way, we developed synthetic biotinylated oligonucleotide probes which complement rRNA of H. pylori. Formalin-fixed and paraffin-embedded tissues from 50 gastric biopsy specimens were examined. Using a serologic test and histochemical stain (Warthin-Starry silver stain and/or Giemsa stain) as a standard, 40 of them were confirmed to be H. pylori-positive. Our ISH was quickly carried out within one hr and results were compared with those obtained from immunohistochemical stain. The ISH produced a positive reaction in 38 of 40 cases (95%). All H. pylori-negative cases failed to demonstrate a positive signal. The ISH has a sensitivity comparable to those of conventional histochemical and immunohistochemical stain, and has high specificity. In conclusion, ISH with a biotinylated oligonucleotide probe provides a useful diagnostic method for detecting H. pylori effectively in routinely processed tissue sections.

Helicobacter Infections↗