BACKGROUND: Left ventricular hypertrophy (LVH) has been known as an important predictor of prognosis of cardiovascular disease. Carboxy-terminal propeptide of procollagen type I (PIP) is related with myocardial fibrosis. We sought to analyze the differences in the characteristics of LVH, myocardial fibrosis, and LV functions among hypertension (HBP), diabetes mellitus (DM) and chronic renal failure (CRF). METHODS: We enrolled consecutive patients with LVH. Patients were grouped as HBP (n=50), DM (n=41), CRF (n=31). Age and sex-matched normal control was also enrolled (n=32). Echocardiography and blood sampling for serum PIP level measuring was performedin all participants. RESULTS: There were no differences in baseline characteristics except systolic blood pressure among four groups. In three patients groups, their LV mass indices were significantly increased than control. Serum PIP level in CRF was much higher than others (CRF 1505.5 vs. HBP 868.7 vs. DM 687.5 vs. control 826.4, p<0.0001). LV diastolic and systolic function evaluated by E', E/E, S' and midwall fractional shortening was significantly decreased in three patients groups. However, LAVi was significantly elevated and LV ejection fraction was significantly decreased in CRF compared to others. In correlation analysis, indices of diastolic function were weakly, but statistically correlated with PIP (E': r=0.234, p=0.006; LAVi: r=0.231, p=0.006). CONCLUSION: In CRF, LV function was more deteriorated and serum PIP was more elevated when compared to HBP or DM. Therefore, myocardial fibrosis may play an important role to LV dysfunction as well as LV hypertrophy in CRF in some degree.
Blood Pressure ; Cardiovascular Diseases ; Collagen Type I ; Diabetes Mellitus ; Echocardiography ; Fibrosis ; Humans ; Hypertension ; Hypertrophy ; Hypertrophy, Left Ventricular ; Kidney Failure, Chronic ; Prognosis

OBJECTIVE: Angiogenesis is central role to both the proliferation and metastasis of malignant tumor. The intense interest in angiogenesis has also lead to a re-examination of the activity of established cytotoxic agents which are known to be an antiangiogenic effect anecdotally. In this study, anti-angiogenic effect of cisplatin, paclitaxel and thalidomide was evaluated in human ovarian cancer cell lines and cervical cancer cell line. METHODS: Human ovarian cancer cell line A2780, cisplatin resistant human ovarian cancer cell line A2780-CDDP, human breast cancer cell line MCF-7, and squamous cell uterine cervical carcinoma cell line SiHa were used to evaluate the level of mRNA and protein expression of VEGF, bFGF and TSP-1, 2 before and after the treatment with cisplatin, paclitaxel, and thalidomide using RT-PCR, protein extraction, and Western blot. The results were analyzed with Wilcoxon signed rank test in the SAS ver 8.1. RESULTS: Targeted mRNAs were synthesized as 212 bp VEGF, 238 bp bFGF, and 492 bp band sized except mRNA of TSP-2 via RT-PCR. The protein of VEGF and bFGF were appeared as 21KDa and 17 KDa size, however, the protein of TSP-1 was not appeared through western blot. No effect of cisplatin on protein expression was measured in these cell lines, but paclitaxel influenced the expression of bFGF in MCF-7 cell line and the expression of TSP-1 in MCF-7 and SiHa cell lines. TSP-1 expression was influenced by thalidomide in A2780 cell line. The protein expression of VEGF and bFGF were not influenced following treatment with cisplatin, paclitaxel, and thalidomide. CONCLUSION: These results were suggested that bFGF and TSP-1 will be used as a target gene for the assay of antiangiogenic effect of paclitaxel in breast and uterine cervical cancer tissue and TSP-1 will be used as that of thalidomide in ovarian cancer. Furthermore, thalidomide will be tried as an adjunctive agent for the improvement of the survival in the case of the patient with ovarian cancer.
Blotting, Western ; Breast ; Breast Neoplasms ; Cell Line* ; Cisplatin ; Cytotoxins* ; Humans ; MCF-7 Cells ; Neoplasm Metastasis ; Ovarian Neoplasms ; Paclitaxel ; RNA, Messenger* ; Thalidomide ; Thrombospondin 1 ; Uterine Cervical Neoplasms ; Vascular Endothelial Growth Factor A

BACKGROUND/AIMS: Tamoxifen is a widely used anticancer drug for breast cancer with frequent gastrointestinal side effects. Changes in gastrointestinal motility is associated with altered activities of membrane ion channels. Ion channels have important role in regulating membrane potential and cell excitability. This study was performed to investigate the effects of tamoxifen on the membrane ionic currents in colonic smooth muscle cells. METHODS: Murine colonic smooth muscle cells were isolated from the proximal colon using collagenase, and the membrane currents were recorded using a whole-cell patch clamp technique. RESULTS: Two types of voltage-dependent K+ currents were recorded (A-type and delayed rectifier K+ currents). Tamoxifen inhibited both types of voltage-dependent K+ currents in a dose-dependent manner. However, tamoxifen did not change the half-inactivation potential and the recovery time of voltage-dependent K+ currents. Chelerythrine, a protein kinase C inhibitor or phorbol 12, 13-dibutyrate, a protein kinase C activator did not affect the voltage-dependent K+ currents. Guanosine 5'-O-(2-thio-diphosphate) did not affect the tamoxifen-induced inhibition of voltage-dependent K+ currents. Tamoxifen inhibited voltage-dependent Ca2+ currents completely in whole-test ranges. CONCLUSIONS: These results suggest that tamoxifen can alter various membrane ionic currents in smooth muscle cells and cause some adverse effects on the gastrointestinal motility.
Animals ; Antineoplastic Agents, Hormonal/*pharmacology ; Calcium Channels/drug effects ; Colon/*drug effects/physiology ; English Abstract ; In Vitro ; Membrane Potentials ; Mice ; Myocytes, Smooth Muscle/*drug effects/physiology ; Potassium Channels/*drug effects ; Tamoxifen/*pharmacology

The interstitial cells of Cajal (ICCs) are the pacemaker cells in gastrointestinal tract and generate electrical rhythmicity in gastrointestinal muscles. Therefore, ICC may be modulated by endogenous agents such as neurotransmitter, hormones, and prostaglandins (PGs). In the present study, we investigated the effects of prostaglandins, especially PGE2, on pacemaker currents in cultured ICCs from murine small intestine by using whole-cell patch clamp techniques. ICCs generated spontaneous slow waves under voltage-clamp conditions and showed a mean amplitude of -452+/-39 pA and frequency of 18+/-2 cycles/min (n=6). Treatments of the cells with PGE2 (1muM) decreased both the frequency and amplitude of the pacemaker currents and increased the resting currents in the outward direction. PGE2 had only inhibitory effects on pacemaker currents and this inhibitory effect was dose-dependent. For characterization of specific membrane EP receptor subtypes, involved in the effects of PGE2 on pacemaker currents in ICCs, EP receptor agonists were used: Butaprost (1muM), EP2 receptor agonist, reduced the spontaneous inward current frequency and amplitude in cultured ICCs (n=5). However sulprostone (1muM), a mixed EP1 and EP3 agonist, had no effects on the frequency, amplitude and resting currents of pacemaker currents (n=5). SQ-22536 (an inhibitor of adenylate cyclase; 100muM) and ODQ (an inhibitor of guanylate cyclase; 100muM) had no effects on PGE2 actions of pacemaker currents. These observations indicate that PGE2 alter directly the pacemaker currents in ICCs, and that the PGE2 receptor subtypes involved are the EP2 receptor, independent of cyclic AMP- and GMP-dependent pathway.
Adenylyl Cyclases ; Dinoprostone* ; Gastrointestinal Tract ; Guanylate Cyclase ; Interstitial Cells of Cajal* ; Intestine, Small* ; Membranes ; Muscles ; Neurotransmitter Agents ; Patch-Clamp Techniques ; Periodicity ; Prostaglandins

OBJECTIVE: Expressions of P-glycoprotein, the multidrug resistance-associated protein (MRP) and the lung resistance protein (LRP) with the MDR phenotype widely divergent in human cancer cell lines. This study focused on the altered gene expression related drug transport. METHODS: To examine correlations between MDR-associated genes and PKC isozyme with cisplatin resistance on the level of the mRNA expression, we analyzed MDR-associated gene (LRP, MDR1/P-gp and MRP) expression and PKC isozyme, topoisomerase II alpha and beta in cisplatin-sensitive ovarian cancer cell line A2780 and cisplatin - resistant cell line A2780cp using cDNA-PCR approach. RESULTS: LRP mRNA levels were significantly increased in A2780cp compared to the drug sensitive variant. In contrast, MRP mRNA levels were not significantly correlated with drug sensitivity. A modest increase in PKC(eta) and MDR1/P-gp mRNA expression activity was also observed in ovarian cancer A2780cp cell lines that were resistant to CDDP. The level of topoisomerase II alpha and beta were not affected. CONCLUSION: These results showed that MDR1/P-gp expression may be an important determinant of the MDR phenotype in cell lines intrinsically resistant to cancer chemotherapeutic agents and a multifactorial emergence of MDR phenotype of tumor with a possible involvement of the PKC isozymes may be associated with CDDP resistant ovarian cancer cell line.
Cell Line* ; Cisplatin ; DNA Topoisomerases, Type II ; Drug Resistance, Multiple* ; Gene Expression ; Humans ; Isoenzymes ; Lung ; Multidrug Resistance-Associated Proteins ; Ovarian Neoplasms* ; P-Glycoprotein ; Phenotype ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger

BACKGROUND: The epidemiologic and clinical features of HIV infection/AIDS are different among various races, regions, and countries. To determine the epidemiologic and clinical characteristics of HIV infection in Korea, we analyzed and compared with that of other populations. METHODS: Medical records of 176 HIV-infected persons in Severance Hospital of Yonsei University College of Medicine and Hospital of Pusan University College of Medicine from year 1985 to 2000 were reviewed retrospectively. RESULTS: One hundred and seventy six patients were analyzed among which 156 (88.6%) were male and 20 (11.4%) were female with a male to female ratio of 7.8:1. At the time of diagnosis, the age distribution was 78 cases (44.3%) in the thirties, 44 cases (25.0%) in the twenties, and 35 cases (19.9%) in the fourties, and the mean age was 35.9+/-9.3. Heterosexual contact was the most frequent transmission route (92 cases, 52.3%), and 42 cases (23.9%) were transmitted by homosexual contact. At initial visit, asymptomatic HIV infection constituted 75 cases (42.6%), and AIDS 72 cases (40.9%). At initial visit, mean value of CD4+ lymphocyte counts was 252/mm3 and HIV RNA 226,035 copies/mm3. One hundred and twenty one of 176 patients developed 317 cases of opportunistic diseases. At the diagnosis of HIV-related opportunistic diseases, mean CD4+ lymphocyte count was 140/mm3 and mean HIV RNA 347,403 copies/mm3. Candidiasis (50 cases, 28.4%) was the most frequent opportunistic disease followed by pneumocystis carinii pneumonia (PCP) (37 cases, 21.0%), tuberculosis (29 cases, 16.5%), cytomegalovirus (CMV) infection (21 cases, 11.9%), HIV encephalopathy (9 cases, 5.1%), and herpes zoster (9 cases, 5.1%). There were 3 cases (1.7%) of malignant lymphoma and 2 cases (1.1%) of Kaposi's sarcoma. At the diagnosis of opportunistic diseases, mean CD4+ lymphocyte counts of patients with candidiasis was 71/mm3, PCP 63/mm3, and tuberculosis 142/mm3, and the mean HIV RNA level was 338,474 copies/mm3, 281,967 copies/mm3, and 817,012 copies/mm3 respectively. Among the 317 opportunistic diseases, AIDS-defining diseases were 150 cases (47.3%), of which PCP was 37 cases (24.7%), tuberculosis 29 cases (19.3%), CMV infection 21 cases (14.0%), HIV wasting syndrome 15 cases (10.0%), and esophageal candidiasis 14 cases (9.3%). The earliest AIDS-defining diseases to manifest in AIDS patients were tuberculosis (25 cases, 33.3%), followed by PCP (17 cases, 22.6%), esophageal candidiasis (14 cases, 18.7%), CMV infection (5 cases, 6.6%), and HIV wasting syndrome (4 cases, 5.3%). Thirty five (19.9%) of 176 patients were died. The common causes of death were tuberculosis (9 cases, 25.7%), PCP (9 cases, 25.7%), bacterial pneumonia (7 cases, 20.0%) and HIV encephalopathy (3 cases, 8.5%). CONCLUSION: The epidemiologic and clinical features of HIV infection/AIDS in Korea are different from that of developing countries such as Southeast Asia and Africa as well as from that of developed countries.
Africa ; Age Distribution ; AIDS Dementia Complex ; Asia, Southeastern ; Busan ; Candidiasis ; Cause of Death ; Continental Population Groups ; Cytomegalovirus ; Developed Countries ; Developing Countries ; Diagnosis ; Epidemiology ; Female ; Herpes Zoster ; Heterosexuality ; HIV Infections ; HIV Wasting Syndrome ; HIV* ; Homosexuality ; Humans ; Korea ; Lymphocyte Count ; Lymphoma ; Male ; Medical Records ; Pneumonia, Bacterial ; Pneumonia, Pneumocystis ; Retrospective Studies ; RNA ; Sarcoma, Kaposi ; Tuberculosis

BACKGROUND: Pemphigus is an autoimmune bullous disease with circulating desmosomal autoantibodies of IgG. In direct IF studies with perilesional tissue, IgA or IgM antibodies can be seen in addition to IgG. OBJECTIVE: We examined sera of patients with pemphigus for the presence/frequency of IgA autoantibodies as well as IgG by indirect IF and immunoblot assay. Patients: Twenty patients of pemphigus (PV 10, PF 10) who showed positive findings in indirect IF examinations. METHODS: Indirect IF study with normal human skin substrates and immunoblot analysis using A431 cell extracts (with multi-step immunostaining) were performed with patients sera. RESULTS: In indirect IF, IgA autoantibodies that bind to the epidermal keratinocyte antigens were detected in 4 cases among the 20 patients (PV 2 and PF 2). In immunoblot analysis IgA bands reacting to PV/PF antigens were observed in 7 cases from the 20 patients with pemphigus (PV 3, PF 4). The serum titers of IgA autoantibodies were lower than those of IgG in every single case. CONCLUSION: In patients with pemphigus (PV/PF), 35% of cases have serum IgA autoantibodies as well as IgG autoantibodies specific to the pemphigus antigens (Dsg 1/Dsg 3). However, pathogenic roles of the associated IgA autoantibody are not clear.
Antibodies ; Autoantibodies ; Cell Extracts ; Humans ; Immunoglobulin A* ; Immunoglobulin G ; Immunoglobulin M ; Keratinocytes ; Pemphigus* ; Skin

OBJECTIVES: There have been several evidences that the central nervous system defect is one of the etiologic factors in schizophrenia and high nailfold plexus visibility can reflect indirectly. These are particularly related to the negative symptoms of schizophrenia. In this study, we examined the relationship between nailfold plexus visibility and various clinical variables in schizophrenia. METHODS: Forty patients(20 males, 20 females) satisfying the DSM-IV criteria for schizophrenia and forty normal controls(20 males, 20 females) were measured for Plexus Visualization Score(PVS) by using capillary microscopic examination. We used Positive and negative Syndrome Scale(PANSS). Uimann-Giovannoni Process-Reactive Questionnaire(PRQ), Phillips Premorbid Adjustment Scale(PAS). Continuous Performance Test, and Backward Masking for psychopathology and clinical variables. RESULTS: There was no significant relationship between schizophrenic subjects and normal controls in PVS. PVS was correlated with PANSS positively except negative symptom subscore. PVS was correlated with PRQ score negatively, and with PAS score positively. CONCLUSIONS: This study shows high PVS are associated with more severe psychotic symptoms and with clinical variables, such as disease process and premorbid adjustment, in some schizophrenics.
Adult* ; Capillaries ; Central Nervous System ; Diagnostic and Statistical Manual of Mental Disorders ; Humans ; Male ; Masks ; Psychopathology ; Schizophrenia

Homeostasis of multicellular organism is controlled by proliferation and differentiation of cells as well as by cell death. The defects in programmed cell death contribute to the pathogenesis of rheumatoid arthritis (RA) and systemic lupus erythematous. RA is considered to be a proliferating disorder of synovial tissue which is accompanied by inflammatory cell infiltration and bone erosion. The aim of the study was to find whether potent inducers of apoptosis could be induced apoptosis in RA synovial cells. We examined the effects of drugs, such as dexamethasone, methotrexate, hydrogen peroxide, and ceramide on induction of apoptosis in cultured RA synovial cells. Used drugs did not induced apoptosis in RA synovial cells. Finally Fas antigen-mediated apoptosis of RA synovial cells was investigated by the addition of anti-Fas antibody. To examine the ICE (interleukin-1p-convertase; caspase-1) expression in synovial cells, RT-PCR of caspase-1 gene was performed. In synovial cells of RA, Fas induces that caspase-1 activation cause apoptosis.
Apoptosis* ; Arthritis, Rheumatoid* ; Cell Death ; Dexamethasone ; Homeostasis ; Humans ; Hydrogen Peroxide ; Ice ; Methotrexate

OBJECTIVES: Human osteoarthritis is a heterogeneous and multifactorial disease characterized by the progressive deterioration of the cartilage of diarthrodial joints. In some instances, there is an identifiable cause, such as trauma or congenital malformation, but, mostly the etiology remains unknown. Since familial aggregation is seen, genetic factors may be important, particularly in osteoarthritis of the hand. METHODS: Blood samples from patients and controls were obtained for DNA analysis. Exon 31 of type II procollagen gene was amplified by polymerase chain reaction, and screening for the mutation was undertaken using a restriction enzyme digestion (Dsa I). RESULTS: The patients phenotype represented typical, but earlyonset and family history, osteoarthritis. No mutation in exon 31 of type II procollagen gene could be identified. CONCLUSION: Screening of the 31 exon did not, however, reveal any mutation. It needs further evaluation in other sites of type II procollagen genes.
Cartilage ; Collagen Type II ; Digestion ; DNA ; Exons ; Hand ; Humans ; Joints ; Mass Screening ; Osteoarthritis* ; Phenotype ; Polymerase Chain Reaction ; Procollagen*