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1.
Transfus Clin Biol ; 26(4): 341-345, 2019 Nov.
Article in English | MEDLINE | ID: mdl-30905678

ABSTRACT

Voluntary non-remunerated donations remain the cornerstone for a safe and sustainable blood supply. According to the World Health Organization and other international scientific committees, all nations must switch their system of blood collection to voluntary non-remunerated donation. Several other types of blood donations still exist nowadays that will be discussed. Lebanon, similarly to other developing countries, is struggling to achieve 100% voluntary non-remunerated donations for the many existing social, demographic, cultural and economic problems. Replacement donations remain the predominant type, which creates huge burden on both hospital blood banks and patient families. Despite the limited resources, some improvements have been made recently in this field and Lebanon seems to be on the road of achieving 100% voluntary non-remunerated blood donation as requested by the World Health Organization. The Lebanese experience is worth sharing so that neighbouring countries facing similar problems could benefit from it.


Subject(s)
Blood Donors , Blood Transfusion , Altruism , Blood Banks/economics , Blood Banks/organization & administration , Blood Banks/statistics & numerical data , Blood Donors/psychology , Blood Donors/statistics & numerical data , Blood Donors/supply & distribution , Blood Transfusion/economics , Blood Transfusion/statistics & numerical data , Developing Countries , Directed Tissue Donation , France , Health Services Needs and Demand , Humans , International Cooperation , Lebanon , Models, Theoretical , Motivation , Private Sector , Remuneration , Volunteers
2.
Haemophilia ; 20(2): 196-9, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24283945

ABSTRACT

To promote management and awareness of bleeding disorders in Lebanon, a pilot programme was launched in 2009 by the Lebanese Hemophilia Association assisted by World Federation of Hemophilia. The aim of this study was to diagnose patients with bleeding disorders and to assess the potential challenges in implementing a screening programme. The pilot project was launched in 26 social health centres in the Bekaa valley. The study tools included the evaluation of the Tossetto Bleeding Score and the Pictorial Bleeding Assessment Chart (PBAC) for menstruation. Persons with a bleeding score higher than 2 and PBAC higher than 185 were eligible for further blood tests including the prothrombin time, partial thromboplastin time, complete blood count, bleeding time and von Willebrand ristocetin cofactor activity. 643 patients were enrolled, of whom 60.6% were women. Overall, 91 persons had an abnormal score. 50 eligible patients were tested: 32 had normal tests, nine new patients with severe Von Willebrand were discovered, 4 had VW:RiCo of 40, 3 prolonged APTT and 2 thrombocytopaenia. There was a clear correlation between the severity of the score and the willingness to perform the tests (P = 0.02). Women were reluctant to participate fully when investigators were men. The probability of adherence to the screening protocol is significantly increased when directed by women health care professional. For patients with milder forms, global screening programmes were neither feasible nor acceptable but those more severely affected have to be identified. Providers are crucial in preselecting patients with blood problems who are not coping well.


Subject(s)
Hemorrhagic Disorders/diagnosis , Hemorrhagic Disorders/epidemiology , Adolescent , Adult , Aged , Child , Child, Preschool , Counseling , Female , Health Surveys , Hematologic Tests , Humans , Lebanon/epidemiology , Male , Middle Aged , National Health Programs , Pilot Projects , Surveys and Questionnaires , Young Adult
3.
IEEE Trans Neural Syst Rehabil Eng ; 21(2): 174-81, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23204287

ABSTRACT

Stroke is one of the leading causes of adult disability with high economical and societal costs. In recent years, novel rehabilitation paradigms have been proposed to address the life-long plasticity of the brain to regain motor function. We propose a hybrid brain-computer interface (BCI)-virtual reality (VR) system that combines a personalized motor training in a VR environment, exploiting brain mechanisms for action execution and observation, and a neuro-feedback paradigm using mental imagery as a way to engage secondary or indirect pathways to access undamaged cortico-spinal tracts. Furthermore, we present the development and validation experiments of the proposed system. More specifically, EEG data on nine naïve healthy subjects show that a simultaneous motor activity and motor imagery paradigm is more effective at engaging cortical motor areas and related networks to a larger extent. Additionally, we propose a motor imagery driven BCI-VR version of our system that was evaluated with nine different healthy subjects. Data show that users are capable of controlling a virtual avatar in a motor imagery training task that dynamically adjusts its difficulty to the capabilities of the user. User self-report questionnaires indicate enjoyment and acceptance of the proposed system.


Subject(s)
Brain-Computer Interfaces , Imagination/physiology , Motor Activity/physiology , Motor Cortex/physiology , Nerve Net/physiology , Neuronal Plasticity/physiology , User-Computer Interface , Adult , Brain Mapping/methods , Evoked Potentials, Motor/physiology , Female , Humans , Male
4.
Clin Med Insights Reprod Health ; 5: 17-24, 2011 May 12.
Article in English | MEDLINE | ID: mdl-24453508

ABSTRACT

BACKGROUND: Systemic Lupus Erythematosus (SLE) has a tendency to occur in women in their reproductive years, causing complications during pregnancy and labour. Conversely, pregnancy can cause flares of disease activity, often necessitating immediate intervention. AIM OF STUDY: to study pregnancy related complications in patients with SLE. PATIENTS AND METHODS: The study included 48 SLE pregnant females. 27 patients with 38 pregnancies, their data viewed retrospectively from medical records, and 21 patients with 21 pregnancies followed up prospectively. The laboratory data included ANA, DNA, APL antibodies and anti Ro/SSA. The disease activity was calculated according to the Systemic Lupus Activity Measure. Ultrasound was performed to confirm gestational age and assess for the presence of any congenital fetal malformations, and then repeated monthly to detect any abnormality including intrauterine growth restriction. At 30 weeks gestation and onwards, assessment of fetal wellbeing including daily fetal kick chart and once weekly non stress test was performed. Doppler blood flow velocimetry was done for those with abnormal fetal heart rate pattern. After labour, the neonate was examined for complications including complete heart block and neonatal lupus. RESULTS: Anti dsDNA was found in 95% of the patients, anti Ro/SSA in 6% and anti APL in 30%. 57% of the patients followed up prospectively had active disease in the 1st trimester, 24% in the 2nd and 62% in the 3rd trimester. The most common maternal complication was preeclampsia 33%, followed by spontaneous abortion 20%. Prematurity was the most common fetal complication 37%, followed by intrauterine growth restriction 29%. 2 neonates were born with congenital heart block and 1 with neonatal lupus. CONCLUSION: Pregnancy in SLE patients is associated with a higher risk of obstetric complications affecting both the mother and the fetus. Preeclampsia was the most common complication followed by prematurity. Preeclampsia was significantly associated with third trimester disease activity.

6.
Clin Lab Haematol ; 23(5): 317-23, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11703415

ABSTRACT

Chronic hepatitis C virus (HCV) infection in many individuals is asymptomatic and the prevalence of antibodies to hepatitis C virus (anti-HCV) among blood donors in Lebanon is scarce. This study aimed to address the prevalence of anti-HCV in 8700 blood donors, the data obtained was compared to other world regions. Between 1997 and 2000, 8700 blood donors were screened for the presence of anti-HCV in their sera. Initially reactive specimens were retested in duplicate, and repeatedly positive samples were subsequently retested by a third generation microplate enzyme immunoassay. Of the 8700 blood donors screened, 51 were confirmed positive for anti-HCV, giving a prevalence rate of 0.6%. While there was no difference in anti-HCV prevalence in relation to age or gender, higher rates were seen in non-Lebanese compared to Lebanese subjects (6.17% vs. 0.48%, P < 0.001). None of the anti-HCV positive individuals had an identifiable risk factor for contracting HCV (intravenous drug user, prior transfusion, etc.), and their transaminases were comparable to anti-HCV-negative donors, suggesting that HCV-positive donors were asymptomatic. These results demonstrate low prevalence of anti-HCV among Lebanese blood donors, which was comparable to those established for Western countries.


Subject(s)
Blood Donors , Hepatitis C Antibodies/blood , Adolescent , Adult , Blood Donors/statistics & numerical data , Female , Hepatitis C/diagnosis , Hepatitis C/prevention & control , Hepatitis C/transmission , Humans , Immunoenzyme Techniques , Lebanon/epidemiology , Male , Mass Screening , Middle Aged , Prevalence , Risk Factors , Seroepidemiologic Studies , Topography, Medical , Transaminases/blood
7.
Transfus Apher Sci ; 24(1): 29-35, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11515608

ABSTRACT

Insofar as chronic hepatitis C virus (HCV) infection in many individuals is asymptomatic, and as the prevalence of antibodies to hepatitis C virus (anti-HCV) among blood donors in Lebanon is scarce, this study addressed the prevalence of anti-HCV in 5,115 blood donors. Data obtained were compared to other world regions. Of the blood donors screened, 57 were initially tested positive or doubtful for anti-HCV Ab. Subsequent testing by two-third generation enzyme immunoassays confirmed that, of the 57 initially tested positive/doubtful, only 18 were positive for anti-HCV giving a prevalence rate of 0.4%. While there was no difference in HCV prevalence with respect to age or gender, a higher rate was seen in non-Lebanese compared to Lebanese subjects (3.4% vs 0.3%, P < 0.001). These results demonstrate a low prevalence of HCV infection among Lebanese blood donors, which was comparable to those established for western countries.


Subject(s)
Blood Donors , Hepatitis C/epidemiology , Adolescent , Adult , Female , Hepatitis C Antibodies/blood , Humans , Immunoenzyme Techniques , Lebanon/epidemiology , Male , Middle Aged , Seroepidemiologic Studies , Topography, Medical
8.
Am J Infect Control ; 29(1): 20-3, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11172314

ABSTRACT

BACKGROUND: Health care workers are at risk of contracting hepatitis C virus (HCV) infection more than the general population, and chronic HCV infection may be asymptomatic. Therefore, the purpose of this study was to determine the seroprevalence of HCV among health care workers at St Georges-Orthodox Hospital, the first study done for a major teaching hospital in Lebanon. METHODS: Health care personnel at St Georges-Orthodox Hospital, Beirut, were offered anonymous testing for anti-HCV antibody. Seroprevalence rates of health care personnel were compared with the rates of blood donors screened during the same year. RESULTS: Of the 502 persons screened, 13 (2.60%) initially tested either positive or doubtful-positive by the SM-HCV rapid test; 2 (0.4%) were confirmed positive by 2 commercial enzyme-linked immunosorbent assay kits and reverse transcriptase-polymerase chain reaction. This prevalence rate was comparable with the rate obtained for blood donors (n = 600) during the same period. CONCLUSION: The seroprevalence of HCV infection among health care workers at St Georges-Orthodox Hospital was similar to the rate observed in local blood donors, which suggests that the occupational risk of HCV infection was low.


Subject(s)
Hepatitis C Antibodies/blood , Hepatitis C/epidemiology , Occupational Diseases/epidemiology , Personnel, Hospital/statistics & numerical data , Adult , Enzyme-Linked Immunosorbent Assay , Female , Hepatitis C/blood , Humans , Lebanon/epidemiology , Male , Middle Aged , Occupational Diseases/blood , Occupational Exposure , Reverse Transcriptase Polymerase Chain Reaction , Seroepidemiologic Studies
9.
Biochem Pharmacol ; 57(2): 195-7, 1999 Jan 15.
Article in English | MEDLINE | ID: mdl-9890568

ABSTRACT

Retinoic acid exerts pleiotropic effects by acting through two families of nuclear receptors, RAR and RXR. All-trans and 9-cis retinoic acid bind RARs, whereas 9-cis retinoic acid binds and activates only the RXRs. To understand the role of human liver cytosolic aldehyde dehydrogenase (ALDH1) in retinoic acid synthesis, we examined the ability of ALDH 1 to catalyze the oxidation of the naturally occurring retinal isomers. ALDH1 catalyzed the oxidation of all-trans, 9-cis, and 13-cis retinal with equal efficiency. However, the affinity to all-trans retinal (Km = 2.2 microM) was twofold higher than to 9-cis (Km = 5.5 microM) and 13-cis (Km = 4.6 microM) retinal. All-trans retinol was a potent inhibitor of ALDH1 activity, and inhibited all-trans retinal oxidation uncompetitively. Comparison of the kinetic properties of ALDH1 for retinal isomers with those of previously reported rat kidney retinal dehydrogenase showed distinct differences, suggesting that ALDH1 may play a different role in retinal metabolism in liver.


Subject(s)
Aldehyde Dehydrogenase/metabolism , Cytosol/enzymology , Isoenzymes/metabolism , Liver/enzymology , Retina/enzymology , Humans , Hydrogen-Ion Concentration , Kinetics
10.
Br J Haematol ; 103(1): 235-42, 1998 Oct.
Article in English | MEDLINE | ID: mdl-9792315

ABSTRACT

Peripheral blood progenitor cells (PBPC) were mobilized and harvested in 200 patients treated for non-Hodgkin's lymphoma (n = 148), Hodgkin's disease (n = 22) and multiple myeloma (n = 30). The variables predicting the collection of a minimal (>2.5 x 10(6)/kg) or a high (>10 x 10(6)/kg) CD34+ cell count were analysed. Patients were mobilized with haemopoietic growth factors following either standard chemotherapy (n = 49) or high-dose cyclophosphamide, given alone (n = 55) or combined with high-dose VP16 (n = 86). 10 patients received haemopoietic growth factors only. The first mobilization resulted in a PBPC harvest with enough CD34+ cells in 179/200 patients (90%). High-dose cyclophosphamide, with or without VP16, did not mobilize a higher progenitor cell yield than standard chemotherapy. When performing multiple regression analysis in the 190 patients who received chemotherapy-containing mobilization, only the number of previous chemotherapy regimens and the exposure to fludarabine predicted for a failure to collect a minimal PBPC count (P=0.06 and 0.0008 respectively). The target to collect a high CD34+ cell count was negatively associated with the number of previous chemotherapy regimens (P=0.002). When only non-Hodgkin's lymphoma patients were considered for multivariate analysis, low-grade histology with fludarabine appeared to be associated with poor PBPC cell yield (P=0.08 and 0.005 respectively). This data confirms that PBPC harvest should be planned early in the disease course in transplant candidates, and can be obtained after a standard course of chemotherapy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cytokines/therapeutic use , Hematopoietic Stem Cell Mobilization/methods , Hodgkin Disease/therapy , Lymphoma, Non-Hodgkin/therapy , Multiple Myeloma/therapy , Adolescent , Adult , Antigens, CD34/metabolism , Female , Hematopoietic Stem Cells/metabolism , Humans , Leukapheresis , Male , Middle Aged , Retrospective Studies , Treatment Outcome
12.
Leukemia ; 12(8): 1281-7, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9697885

ABSTRACT

Mantle cell lymphoma (MCL) patients represent a difficult problem, sometimes to establish the diagnosis but mostly because of their refractoriness to standard lymphoma treatments. Which treatments to apply and to whom is not yet defined. In this study, we attempted to analyze the clinical features, to identify the major prognostic factors, and to evaluate the outcome of 121 MCL patients treated in our institution between 1979 and 1997. Clinical data, treatment modalities, and International Prognostic Index (IPI) score were evaluated. Median age was 63 years. Patients usually presented with advanced stage disease (87%), disseminated lymph nodes (57%), bone marrow involvement (79%), but with a good performance status (PS) (81%). Lymphocytosis >4000/microl and/or peripheral blood involvement was present in 36% of cases, and gastrointestinal disease in 18%. The t(11;14)(q13;q32) and/or bcl-1 rearrangement was detected in 47/57 studied cases. Median overall survival (OS) was 3.12 years and a longer survival was significantly associated with younger age (<70 years), good PS (<2), localized disease (stage I-II), fewer than two extra-nodal sites, absence of spleen or peripheral blood involvement, normal serum LDH and beta2-microglobulin levels, and hemoglobin level greater than 12 g/dl. However, the IPI failed to identify patients with longer OS and in a multiparametric analysis, only older age, hemoglobin less than 12 g/dl, poor PS, and blood involvement were associated with a poorer outcome. Treatment modalities had no impact on survival with 75% of patients relapsing or progressing. Our data showed that the poor outcome of MCL patients is mainly related to adverse patient characteristics, a highly disseminated tumor, and some unknown parameters associated with the refractoriness to standard therapy.


Subject(s)
Lymphoma, Non-Hodgkin/physiopathology , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Female , Humans , Immunophenotyping , Lymphoma, Non-Hodgkin/drug therapy , Lymphoma, Non-Hodgkin/immunology , Male , Middle Aged , Outcome Assessment, Health Care , Prognosis , Retrospective Studies
13.
Cancer Epidemiol Biomarkers Prev ; 6(9): 699-704, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9298577

ABSTRACT

Studies in laboratory animals have demonstrated that dietary supplements of organoselenium, 1,4-phenylenebis(methylene)selenocyanate (p-XSC) inhibit colon carcinogenesis. Diverse chemopreventive agents and clinically used anticancer drugs have been shown to induce apoptosis in colonic tumors. Inducing apoptosis is a key mechanism for the effectiveness of some chemopreventive agents; however, failure of apoptosis is now believed to contribute to the development of human cancer. In this study, we determined the number of apoptotic bodies in the colon tumors of rats fed a low-fat (LF) or a high-fat (HF) diet with or without p-XSC treatment. At 5 weeks of age, male F344 rats were divided into four groups, which were then maintained on one of the following diets: LF, 5% corn oil; HF, 23.5% corn oil; and LF and HF supplemented with 20 ppm p-XSC. In addition, the LF or HF diet with p-XSC supplements was administered either during the initiation stage or postinitiation. At 7 weeks of age, all rats except those intended for vehicle (normal saline) treatment were given 15 mg/kg of body weight of azoxymethane once weekly for 2 weeks. The animals were sacrificed 38 weeks after carcinogen treatment, and their colonic tumors were examined for appearance of apoptosis. The LF diet significantly increased the percentage of apoptosis as compared to the HF diet; the percentage of apoptosis in LF and HF diets were 12.4 and 2.9. The colon tumors that were present in the groups fed p-XSC together with a LF or a HF diet after carcinogen administration (postinitiation period) had a higher number of apoptotic bodies than those that were present in the animals fed p-XSC before carcinogen treatment (initiation period). The extent of apoptosis was weak when p-XSC was given with a HF diet (4.4%) during the initiation phase, but it was high significant when p-XSC was administered with LF diet (25.2%). Taken together, our data suggest that administration of LF diet supplemented with p-XSC increases apoptosis as compared to a HF diet alone.


Subject(s)
Anticarcinogenic Agents/pharmacology , Apoptosis/drug effects , Colonic Neoplasms/prevention & control , Dietary Fats/administration & dosage , Organoselenium Compounds/pharmacology , Animals , Azoxymethane , Carcinogens , Colonic Neoplasms/chemically induced , Colonic Neoplasms/genetics , Colonic Neoplasms/pathology , Male , Rats , Rats, Inbred F344
14.
Cancer Res ; 57(7): 1301-5, 1997 Apr 01.
Article in English | MEDLINE | ID: mdl-9102217

ABSTRACT

Recent evidence supports the theory that tumor growth in vivo depends on evasion of normal homeostatic control mechanisms that operate through induction of cell death by apoptosis. This study tested the hypothesis that several potential chemopreventive agents share the ability to induce apoptosis and that inhibition of apoptosis is a mechanism of tumor promoters. The present study was designed to investigate whether the chemopreventive properties of sulindac, curcumin, and phenylethyl-3-methylcaffeate (PEMC) and the tumor-promoting activity of 6-phenylhexyl isothiocyanate (PHITC) that were observed in our previous studies are associated with the induction or inhibition of apoptosis in azoxymethane (AOM)-induced colon tumors in male F344 rats. At 5 weeks of age, groups of rats were fed control (modified AIN-76A) diet or diets containing 320 ppm of sulindac, 2000 ppm of curcumin, 750 ppm of PEMC, or 640 ppm of PHITC. At 7 weeks of age, all rats except those intended for vehicle (normal saline) treatment were given AOM (15 mg/kg body weight) once weekly for 2 weeks. To study the effect of sulindac administered during promotion/progression stage, the rats were fed the control diet initially and then fed the experimental diet containing 320 ppm of sulindac 14 weeks after the second AOM treatment. The rats were sacrificed 52 weeks after carcinogen treatment, and their colonic tumors were subjected to histopathological evaluation and the appearance of apoptosis. In the current study, chronic administration of sulindac, curcumin, and PEMC or sulindac given only during promotion/progression significantly increased the apoptotic index (percentage of apoptosis) as compared to administration of the control diet; the apoptotic indices in the control, sulindac, curcumin, and PEMC diets were 8.3, 17.6, 17.7, and 18.5%, respectively, and in sulindac administered during promotion/progression stage, the apoptotic index was 19.1%. However, dietary PHITC blocked the process of apoptosis during colon carcinogenesis. The apoptotic index in PHITC diet was 7.0%. Taken together, our data show that chemopreventive properties of agents are correlated with the degree of apoptosis. Therefore apoptosis seems to be a reliable biomarker for the evaluation of potential agents for cancer prevention.


Subject(s)
Adenocarcinoma/prevention & control , Anticarcinogenic Agents/pharmacology , Apoptosis/drug effects , Azoxymethane , Colonic Neoplasms/prevention & control , Adenocarcinoma/chemically induced , Adenocarcinoma/pathology , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Biomarkers, Tumor , Caffeic Acids/pharmacology , Carcinogens , Colonic Neoplasms/chemically induced , Colonic Neoplasms/pathology , Curcumin/pharmacology , Isothiocyanates/pharmacology , Male , Rats , Rats, Inbred F344 , Sulindac/pharmacology
15.
Cancer Res ; 57(3): 420-5, 1997 Feb 01.
Article in English | MEDLINE | ID: mdl-9012468

ABSTRACT

Epidemiological studies suggest that consumption of diets containing fruits and vegetables, major sources of phytochemicals and micronutrients, may reduce the risk of developing cancer of the colon. Several phytochemicals and micronutrients present in fruits and vegetables are known to exert cancer-chemopreventive effects in several organs, including the colon. Monoterpenes such as d-limonene and perillyl alcohol derived from orange peels and lavender, respectively, have been shown to possess chemopreventive properties against mammary, liver, and/or lung carcinogenesis. The present study was designed to investigate the efficacy of dietary 40 and 80% maximum tolerated dose (MTD) levels of perillyl alcohol on azoxymethane (AOM)-induced colon carcinogenesis. The effect of this agent on the process of apoptosis in colon tumors was also investigated. Prior to the efficacy study, the MTD of perillyl alcohol was determined in male F344 rats in a 6-week subchronic toxicity study and found to be a 2.5-g/kg diet when added to the AIN-76A diet. At 5 weeks of age, groups of male F344 rats were fed control (AIN-76A) diet or diets containing 1 and 2 g perillyl alcohol/kg diet, representing 40 and 80% MTD levels, respectively. At 7 weeks of age, all animals except those in the vehicle-treated groups were given two weekly s.c. injections of AOM (15 mg/kg body weight/week). All animals were continued on their respective dietary regimen for 52 weeks after AOM treatment and then sacrificed. Colon tumors were evaluated histopathologically using routine procedures. Perillyl alcohol at the 1-g/kg level significantly inhibited the incidence (percentage of animals with tumors) and multiplicity (tumors/ animals) of invasive adenocarcinomas of the colon, whereas perillyl alcohol at 2 g/kg diet inhibited the incidence of total adenocarcinomas of the colon and small intestine as compared to the control diet. Our studies also indicate that the colon tumors of animals fed perillyl alcohol exhibited increased apoptosis as compared to those fed the control diet. These results demonstrate the potential chemopreventive activity of perillyl alcohol against colon carcinogenesis. The chemopreventive activity of perillyl alcohol is mediated through the tumor cell loss by apoptosis.


Subject(s)
Adenocarcinoma/prevention & control , Anticarcinogenic Agents/administration & dosage , Colonic Neoplasms/prevention & control , Monoterpenes , Terpenes/administration & dosage , Animals , Apoptosis/drug effects , Azoxymethane/toxicity , Diet , Male , Rats , Rats, Inbred F344
16.
J Rheumatol ; 24(12): 2451-60, 1997 Dec.
Article in English | MEDLINE | ID: mdl-9415657

ABSTRACT

OBJECTIVE: To investigate the effect of synovial fluid (SF) from patients with juvenile rheumatoid arthritis (JRA) on proliferation and induction of degradative and invasive phenotype in normal synovial fibroblasts, and to elucidate the contribution of SF cells to this activity. METHODS: SF and/or conditioned medium (CM) from SF cells were evaluated for their ability to (1) stimulate a proliferative response, (2) induce the "activated phenotype" capable of invading cartilage matrix, and (3) promote the release of key matrix metalloproteinases (MMP) in normal synovial fibroblasts. RESULTS: Proliferation of normal synovial fibroblasts exposed to SF or CM from SF cells of patients with JRA was up to 3 times greater than untreated controls. Concomitant with induction of an activated phenotype in the treated synovial fibroblasts, the activated form exhibited up to 250% invasiveness of cartilage matrix compared to untreated synovial fibroblasts (100%), in addition to releasing increased MMP activity, not normally associated with these quiescent cells. This induction was not solely due to tumor necrosis factor-alpha, transforming growth factor-beta, interleukin 1beta (IL-1beta), and IL-6, as SF and/or CM depleted of these cytokines sustained about 40% of their invasive and inducing ability. We observed that the mononuclear cell (MNC) population that infiltrated into the joint cavity secretes this "inducing activity," which can be maintained in culture up to several weeks. CONCLUSION: Our data suggest that the cellular component of SF releases soluble factor(s) that directly or indirectly contribute to (a) proliferation of synovial fibroblasts, and (b) production and release of extracellular MMP by synovial fibroblasts, thereby inducing a degradative and invasive phenotype culminating in cartilage and bone destruction.


Subject(s)
Arthritis, Juvenile/metabolism , Monocytes/immunology , Synovial Fluid/cytology , Synovial Membrane/cytology , Antibodies , Arthritis, Juvenile/immunology , Binding, Competitive/immunology , Cartilage/cytology , Cell Division/physiology , Cells, Cultured , Enzyme-Linked Immunosorbent Assay , Female , Fibroblasts/enzymology , Fibroblasts/immunology , Fibroblasts/pathology , Humans , Immunophenotyping , Interleukin-1/immunology , Interleukin-6/immunology , Male , Metalloendopeptidases/metabolism , Monocytes/cytology , Monocytes/metabolism , Neutralization Tests , Synovial Fluid/immunology , Synovial Membrane/immunology , Transforming Growth Factor beta/immunology , Tumor Necrosis Factor-alpha/immunology
17.
Leuk Lymphoma ; 19(1-2): 95-105, 1995 Sep.
Article in English | MEDLINE | ID: mdl-8574172

ABSTRACT

In this study, we examined the effect of different concentrations of sodium deoxycholate (NaDOC), a secondary bile salt, on an Epstein-Barr virus transformed human lymphoid cell line (NC-37). We found that NaDOC induces classic apoptosis in a dose-dependent manner at 0.1-0.4 mM doses, and necrosis at much higher concentrations (0.8-3.1 mM). This is the first demonstration that a bile salt can induce apoptosis in any cell type. The mode of cell death was determined using morphologic methods (light and electron microscopy) as the gold standard. Standard agarose gel electrophoretic techniques were applied to identify the "ladder" of DNA fragments that have been associated with apoptosis in certain cell types. Although DNA fragmentation was observed during the apoptotic death of NC-37 cells, we were not able to identify a "ladder" pattern of fragmentation. Two other types of cells, however, that previously have been reported to display a characteristic "ladder" pattern of DNA fragmentation, glucocorticoid-treated WEHI7.2 cells and isolated human neutrophils, did display the "ladder" pattern. This study emphasizes the need to examine morphology when identifying the mode of cell death induced by a new agent.


Subject(s)
Apoptosis , Cell Transformation, Viral , DNA Damage , DNA/analysis , Deoxycholic Acid/pharmacology , Herpesvirus 4, Human/genetics , Lymphocytes/physiology , Apoptosis/drug effects , Cell Line, Transformed , DNA/isolation & purification , Dose-Response Relationship, Drug , Electrophoresis, Agar Gel/methods , Humans , Kinetics , Lymphocytes/drug effects , Lymphocytes/ultrastructure , Microscopy, Electron
18.
Curr Eye Res ; 14(7): 611-7, 1995 Jul.
Article in English | MEDLINE | ID: mdl-7587308

ABSTRACT

Like corneal endothelial cells, human trabecular meshwork cells are believed to be of neural crest origin, but demonstrate physiological properties and an antithrombogenic surface similar to vascular endothelial cells. One current method for isolating trabecular meshwork cells utilizes the motile nature of these cells to migrate away from a trabecular meshwork explant in culture to more distal regions of the culture dish. This 'outgrowth' technique is limited in practice by the relatively small number of cells that migrate per explant per unit time, thus hindering the ability to gather sufficient numbers of cells for comprehensive experimentation. For this reason, we have modified an extracellular matrix digestion technique in current use for the isolation of microvascular endothelial cells to isolate human trabecular meshwork cells. This procedure is both efficient and rapid for isolating large numbers of trabecular meshwork cells and results in the availability of trabecular meshwork cells in sufficient quantities for subsequent experimentation.


Subject(s)
Collagenases/metabolism , Extracellular Matrix/metabolism , Trabecular Meshwork/cytology , Adolescent , Adult , Aged , Biomarkers/analysis , Cell Separation/methods , Cells, Cultured , Child , Child, Preschool , Humans , Immunoenzyme Techniques , Infant , Infant, Newborn , Middle Aged , Tissue Plasminogen Activator/analysis , Trabecular Meshwork/chemistry , Trabecular Meshwork/drug effects , Trabecular Meshwork/physiology
19.
Pediatr Res ; 31(3): 280-5, 1992 Mar.
Article in English | MEDLINE | ID: mdl-1561016

ABSTRACT

The elastic laminae in a vessel provide resilience to its wall. In perinatal and adult rats, we used in situ hybridization to localize the mRNA for tropoelastin (TE) in endothelial cells, medial smooth muscle cells, and adventitial fibroblasts of pulmonary arteries and veins to determine the contribution of these cells to laminae formation. We found that 1) all three cell types are elastogenic but for each the ontogenic pattern is different, 2) signal in the artery is strongest in the late fetal lung, 3) postnatally TE expression decreases first in the outer medial smooth muscle cells, and 4) the pattern of expression in arteries differs from that in veins. In the d 19 fetus, the signal for TE mRNA was higher in arteries than in veins. In the immediate postnatal period, the arterial signal declined, whereas the signal in veins increased. By postnatal d 21, the arterial TE signal per cell had significantly decreased to an intensity lower than that in veins. In the adult rat lung, no TE mRNA was detected by in situ hybridization. The reciprocal alterations in TE expression in pulmonary arteries and veins may suggest a response to the postnatal change in pulmonary blood pressure. We speculate that because all three cell types are potentially elastogenic they may all play a role in the remodeling that occurs after vascular injury.


Subject(s)
Pulmonary Artery/metabolism , Pulmonary Veins/metabolism , Tropoelastin/genetics , Animals , DNA Probes , Elastic Tissue/embryology , Elastic Tissue/growth & development , Elastic Tissue/metabolism , Endothelium, Vascular/embryology , Endothelium, Vascular/growth & development , Endothelium, Vascular/metabolism , Female , Fetus/metabolism , Fibroblasts/metabolism , Gene Expression , Muscle Development , Muscle, Smooth, Vascular/embryology , Muscle, Smooth, Vascular/growth & development , Muscle, Smooth, Vascular/metabolism , Pregnancy , Pulmonary Artery/embryology , Pulmonary Artery/growth & development , Pulmonary Veins/embryology , Pulmonary Veins/growth & development , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Rats, Inbred Strains
20.
Am J Respir Cell Mol Biol ; 5(6): 571-8, 1991 Dec.
Article in English | MEDLINE | ID: mdl-1720320

ABSTRACT

Gene expression for tropoelastin, the proprotein for elastin, was examined in the rat lung from 17 days of gestation (pseudoglandular stage) to adulthood by in situ hybridization using a rat-specific 35S-radiolabeled riboprobe. The tropoelastin message was present in vascular and airway smooth muscle, endothelial, septal interstitial, alveolar wall, and mesothelial cells but not in epithelial cells. With alveolar septal formation, the message in the interstitium increased progressively from 17 days of gestation, reaching a peak at 7 to 11 days postnatal. The signal in the arterial walls, in contrast, peaked between 19 days of gestation to 1 day postnatal and thereafter declined first from the outer media. The signal in general declined significantly by 21 days postnatal, and elastogenesis was virtually absent in the adult. These results support the idea that tropoelastin gene expression in the interstitium is closely associated with the centripetal progression of alveolarization, and the early postnatal decrease of tropoelastin expression in blood vessels corresponds with the sudden postnatal changes in the pulmonary hemodynamics. Furthermore, in the rat fetus and neonate, endothelial cells expressed the gene for tropoelastin and hence probably play a significant role in the formation of internal elastic lamina in vivo.


Subject(s)
Gene Expression/physiology , Lung/physiology , Tropoelastin/genetics , Animals , Animals, Newborn , Blotting, Northern , Female , Fetus , Lung/blood supply , Lung/embryology , Lung/growth & development , Nucleic Acid Hybridization , RNA , RNA Probes , RNA, Complementary , Rats , Rats, Inbred Strains
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