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Biomedical subjects

L Sen

Publications and source records attributed to L Sen.

At least 55 records · Page 3Linked to original sources
PubMed1994

Effects of amiodarone, sematilide, and sotalol on QT dispersion.

To study the effects of class III agents on QT/QTc dispersion in patients with heart disease and cardiac arrhythmias, QT dispersion and QRS and RR intervals were compared in patients before and after treatment with amiodarone (n = 26), sematilide (n = 26), and sotalol (n = 26). QT, QRS, and RR intervals, and QTc values were calculated for each complex, and their mean values were calculated for each lead. QT and QTc dispersions were defined as differences between the minimal and maximal QT or QTc values in each of the 12 leads studied. Amiodarone, sematilide, and sotalol all significantly prolonged the QT interval and the QTc value. Significant reductions in QT and QTc dispersions were only found in the amiodarone group (QT dispersions: 79 +/- 13 vs 49 +/- 14 ms; p < 0.001; QTc dispersions: 0.08 +/- 0.02 vs 0.05 +/- 0.01 s1/2; p < 0.001). The mean RR interval was significantly increased in patients after treatment with amiodarone (p < 0.001) and sotalol (p < 0.001), but not in patients receiving sematilide treatment (p > 0.2). The baseline QT and QTc dispersions were significantly greater in patients with than without myocardial infarction before treatment (p < 0.001). The mean baseline values for QT/QTc dispersions were not significantly different among all 3 groups. However, only amiodarone significantly reduced the QT dispersion (from 76 +/- 10 to 46 +/- 11 ms; p < 0.001) and QTc dispersion (from 0.09 +/- 0.02 to 0.05 +/- 0.01 s1/2; p < 0.001) in patients with myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Decreased phagolysosomal fusion of peripheral blood monocytes from patients with thalassemia major.

We evaluated the phagolysosomal fusion of peripheral blood monocytes from 15 patients with thalassemia major and 10 thalassemia major carriers using a cytomorphological method with acridine orange as fusion marker. The monocyte phagolysosomal fusion of thalassemic patients was decreased (49.6 +/- 8.6%, mean +/- SD) and differed significantly (p < 0.05) from those of carriers and normal controls (65.7 +/- 11.4% and 74.6 +/- 5.7%, respectively). In vitro deferoxamine partially improved monocyte phagolysosomal fusion of patients with thalassemia major, and did not affect monocyte function in carriers and healthy subjects. Furthermore, in vitro addition of ferrous sulfate decreased normal phagolysosomal fusion. We conclude that the monocyte phagolysosomal fusion dysfunction of thalassemic patients could be related to iron overload.

Adolescent↗
PubMed1994

T-type Ca2+ channels are abnormal in genetically determined cardiomyopathic hamster hearts.

Although there is substantial evidence of abnormal Ca2+ homeostasis in heart cells of the cardiomyopathic Syrian hamster (Bio 14.6 strain), the mechanism by which these myocytes become Ca(2+)-overloaded is not known. To elucidate the role of voltage-sensitive Ca2+ channels in the pathogenesis of myopathy, whole-cell Ca2+ currents were measured in myopathic and normal control cardiac myocytes. These studies demonstrate the presence of two voltage-sensitive Ca2+ channel types in ventricular myocytes isolated from 200- to 300-day-old cardiomyopathic and age-matched normal hamsters. The two Ca2+ channel types were identified by their unitary conductance properties and pharmacologic sensitivities. Both L-type and T-type Ca2+ channels were present in cardiomyopathic and normal cells. Current density through L-type Ca2+ channels was the same in cardiomyopathic and normal control myocytes. However, the mean current density of T-type Ca2+ channels in cardiomyopathic cells was significantly higher than in normal cells (myopathic, 12.3 +/- 1.8 pA/pF; normal, 5.8 +/- 1.1 pA/pF; n = 8; P < .01). The T-type Ca2+ current in cardiomyopathic myocytes was activated and inactivated at more negative potentials than in cells from normal hamster hearts. These findings demonstrate no abnormality of the dihydropyridine-sensitive voltage-dependent L-type Ca2+ channel. In contrast, the observed abnormalities in T-type Ca2+ channel function in cardiomyopathic hamster myocytes suggest that this alteration may be related to the pathogenesis of Ca2+ overload and the arrhythmias in this genetically determined form of cardiomyopathy.

Animals↗
PubMed1993

Impaired phagolysosomal fusion of peripheral blood monocytes from HIV-infected subjects.

We evaluated phagolysosomal fusion in peripheral blood monocytes from 20 HIV-infected individuals and 40 normal controls, using a fluorescence assay with acridine orange as marker. The percentages of phagolysosomal fusion of monocytes from HIV-infected subjects, after 30 and 60 min of yeast ingestion, (mean +/- standard deviation) 57.2 +/- 17 and 63.2 +/- 18.6, respectively, when compared to normal controls (72.4 +/- 7.8 and 77 +/- 8.1), did not differ significantly. However, there was a direct linear association between the percentages of phagolysosomal fusion and CD4+ lymphocytes (P < 0.001) or CD4/CD8 T-cell ratio (P < 0.01). These results suggest that phagolysosomal dysfunction becomes evident at late stages of HIV infection and progresses as CD4+.T-lymphocyte count and CD4/CD8 T-cell ratio decrease. On the other hand, recombinant gp120 inhibited significantly normal phagolysosomal fusion at concentrations ranging between 1 and 1000 ng/ml. Taking together the results obtained, we can conclude that gp120 could be responsible for monocyte phagolysosomal dysfunction observed in HIV infected patients.

Adult↗
PubMed1993

[Neutrophil chemotactic dysfunction in multitransfused thalassemia patients].

PURPOSE: To evaluate the chemotactic capability of neutrophils in thalassaemic patients under poly-transfusion regimens and in thalassaemia carriers. PATIENTS AND METHODS: Twenty-one patients in multi-transfusion regimen diagnosed in the Ricardo Gutiérrez Children Hospital were studied. Of them, 17 had thalassaemia major, 3 S/beta thalassaemia and one sickle-cell anaemia. Twenty-one normal subjects comprised a control group. Chemotaxis was evaluated by two methods, namely, migration under agarose layer and in microchemotaxis chamber under stimulation with N-formyl-methionyl-n-phenylalanine at optimal concentrations of 10(-5) M and 10(-6) M, respectively. RESULTS: In thalassaemia major patients, directed mobility of neutrophil assessed by both methods was significantly decreased with regard to the normal controls, whereas random mobility was preserved. The four patients under poly-transfusion who had not thalassaemia major showed the same neutrophil defect. On the contrary, chemotaxis and random mobility of the neutrophils from thalassaemia carriers (thalassaemia minor) were similar to those of the normal controls. CONCLUSIONS: These results suggest that the defect found in the patients might be caused by transfusion overload.

Adolescent↗
PubMed1992

Impaired in vitro growth of purified (CD34+) hematopoietic progenitors in human immunodeficiency virus-1 seropositive thrombocytopenic individuals.

In this report the role played by human immunodeficiency virus type-1 (HIV-1) in the pathogenesis of HIV-1-related thrombocytopenia was investigated. CD34+ hematopoietic stem/progenitor cells were purified from the bone marrow (BM) of HIV-1(+) thrombocytopenic patients, HIV-1(+) nonthrombocytopenic individuals, HIV-1(-) patients with immune thrombocytopenic purpura, and HIV-1(-) normal donors. CD34+ cells from HIV-1(+) thrombocytopenic individuals alone showed a reduced capacity to give rise to megakaryocytic colonies (CFU-Meg) and also a progressive and significant decline in cell number when placed in liquid culture containing recombinant human interleukin-3 (rIL-3). This decline involved not only megakaryocyte but also erythroid and granulocyte/macrophage progenitors. The defects in megakaryocyte colony formation and CD34+ cell growth did not result from a productive HIV-1 infection of CD34+ cells. Moreover, HIV-1 DNA was absent from CD34+ cells in 10 of 12 thrombocytopenic patients examined. On the other hand, the decreased survival/proliferation of CD34+ cells in liquid culture, within the HIV-1(+) thrombocytopenic patients, was correlated with the presence of HIV-1 p24 antigen in BM plasma. These results demonstrate an impairment of CD34+ cells in HIV-1(+) individuals presenting thrombocytopenia as the only hematologic manifestation. Furthermore, these findings suggest that increased viral replication in the BM microenvironment may cause this impairment and possibly contributes to HIV-induced thrombocytopenia.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Cholesterol increases the L-type voltage-sensitive calcium channel current in arterial smooth muscle cells.

To determine whether membrane free cholesterol affects calcium currents in vascular smooth muscle cells, whole-cell patch clamp recordings were made before and after cholesterol enrichment of cells by exposure to cholesterol-rich liposomes. Exposure to cholesterol-rich liposomes resulted in a gradual increase in the L-type current over 20 hours and a plateau (73 +/- 7% increase over basal) between 20 and 32 hours. This effect was associated with a rightward shift in the inactivation potential and a decrease in the sensitivity to (-)-PN-202-791, a dihydropyridine antagonist. There was no change in the maximum L-type current stimulated by (+)-PN-202-791, a dihydropyridine agonist. Liposome exposure caused a small, transient increase in the T-type current (peak effect, 20 minutes). We conclude that membrane cholesterol has important effects on the L-type calcium current in vascular smooth muscle cells, which is most likely due to an alteration in channel functional state rather than an increase in channel expression.

Animals↗
PubMed1992

Direct contact between sympathetic neurons and rat cardiac myocytes in vitro increases expression of functional calcium channels.

To test the hypothesis that direct contact between sympathetic neurons and myocytes regulates expression and function of cardiac Ca channels, we prepared cultures of neonatal rat ventricular myocytes with and without sympathetic ganglia. Contractile properties of myocytes were assessed by an optical-video system. Contractility-pCa curves showed a 60% greater increase in contractility for innervated myocytes compared with control cells at 6.3 mM [Ca]0 (n = 8, P less than 0.05). Cells grown in medium conditioned by growth of ganglia and myocytes were indistinguishable physiologically from control cells. [Bay K 8644]-contractility curves revealed a 60 +/- 10% enhancement of the contractility response at 10(-6) M for innervated cells compared with control cells. The increased response to Bay K 8644 was not blocked by alpha- or beta-adrenergic antagonists. Moreover, increased efficacy of Bay K 8644 was maintained for at least 24 h after denervation produced by removal of ganglia from the culture. Dihydropyridine binding sites were assessed with the L channel-specific radioligand 3[H]PN200-110. PN200-110 binding sites were increased by innervation (51 +/- 5 to 108 +/- 20 fmol/mg protein, P less than 0.01), with no change in KD. Peak current-voltage curves were determined by whole-cell voltage clamp techniques for myocytes contacted by a neuron, control myocytes, and myocytes grown in conditioned medium. Current density of L-type Ca channels was significantly higher in innervated myocytes (10.5 +/- 0.4 pA/pF, n = 5) than in control myocytes (5.9 +/- 0.3 pA/pF, n = 8, P less than 0.01) or myocytes grown in conditioned medium (6.2 +/- 0.2 pA/pF, n = 10, P less than 0.01). Thus, physical contact between a sympathetic neuron and previously uninnervated neonatal rat ventricular myocytes increases expression of functional L-type calcium channels as judged by contractile responses to Ca0 and Bay K 8644, as well as by electrophysiological and radioligand binding properties.

Animals↗
PubMed1991

Lymphocyte subpopulations and cytokine production in paracoccidioidomycosis patients.

Despite the postulated role of the immune system in the control of the infection by Paracoccidioides brasiliensis, only a few studies have addressed this point in patients. The determination of total lymphocytes and their subpopulations in 6 untreated patients with the chronic form of paracoccidiodomycosis showed that half of them were lymphopenic, because of low number of CD4+ T-lymphocytes. All patients had low CD4/CD8 ratios. On the contrary, B-lymphocytes were normal in all patients. An additional patient, studied on treatment with ketoconazole, had normal lymphocyte counts in all subpopulations, as did one of the patients previously studied at diagnosis when he received specific antimycotic treatment. The production of interferon and tumor necrosis factor, determined by bioassay in supernatants of mononuclear blood cells of the patients, induced by interleukin 2 in vitro was significantly lower than that of normal subjects. These results show that patients with paracoccidioidomycosis have a defect in blood lymphocyte subsets as well as in the ability to produce regulatory cytokines.

Adult↗
PubMed1990

Enhanced alpha 1-adrenergic responsiveness in cardiomyopathic hamster cardiac myocytes. Relation to the expression of pertussis toxin-sensitive G protein and alpha 1-adrenergic receptors.

The pathogenesis of the myopathy occurring in the heart of the cardiomyopathic strain of the Syrian hamster is not well understood but is believed to be associated with abnormal calcium handling by myopathic cells. The purpose of this study was to determine whether the cardiomyopathy occurring in strain BIO 14.6 animals is associated with an enhanced alpha 1-adrenergic receptor-mediated rise in cytosolic calcium, whether a pertussis toxin-sensitive G protein is involved in coupling the alpha 1-adrenergic receptor to changes in intracellular calcium and whether enhanced alpha 1 responsiveness is associated with an increase in the level of expression of the alpha 1-adrenergic receptor or in the pertussis toxin-sensitive G protein or proteins. To test the hypothesis that the cardiomyopathic state is associated with a greater alpha 1-receptor-mediated rise in cytosolic calcium, we studied the effect of phenylephrine (in the presence of propranolol) on time-averaged cytosolic calcium concentration ([Ca2+]i) in isolated cardiac myocytes from cardiomyopathic and age-matched control hamsters. Phenylephrine caused a greater increase both in time-averaged [Ca2+]i (an increase of 48 +/- 8% versus 12 +/- 3%, p less than 0.01) and in contractility (+181 +/- 22% versus +35 +/- 9%, p less than 0.01) in cardiomyopathic than in normal cardiac myocytes. Exposure to pertussis toxin (200 ng/ml for 3 hours) attenuated the alpha 1-adrenergic receptor-mediated increase in contractility and time-averaged [Ca2+]i in both cardiomyopathic and normal cells. The level of pertussis toxin-sensitive G protein, as determined by pertussis toxin-mediated [32P]ADP-ribosylation, was 1.6-fold higher in cardiomyopathic versus normal hamster hearts. The density of alpha 1-adrenergic receptors, as measured by the antagonist radioligand [3H]prazosin and the affinity of the receptor for agonist and antagonist were similar in myopathic and normal heart membranes. Thus, in cardiac myocytes from hamsters, the alpha 1-adrenergic receptor-mediated effects on [Ca2+]i and contractility appear to be mediated by a pertussis toxin-sensitive G protein or proteins. In myocytes from cardiomyopathic hamsters, these alpha 1-adrenergic effects were increased in magnitude, as was the level of pertussis toxin-sensitive G protein, but there was no measurable alteration in the density or ligand binding properties of alpha 1-adrenergic receptors.

Animals↗
PubMed1990

Properties of adult rat ventricular cells in long-term culture.

Adult mammalian cardiac myocytes in long-term culture offer advantages over intact heart tissue and freshly isolated ventricular cell preparations for a variety of experimental studies. To characterize this preparation in detail, we have examined the physiological properties of isolated adult rat ventricular cells maintained in culture for 10-14 days. Adult rat myocytes in longterm culture contracted spontaneously, with electrical coupling of adjacent cells, at 1-3 Hz. Most myocytes showed myofibrils with well-developed mitochondria and transverse tubular systems. They showed predominantly the V1 type myosin heavy chain isoform. In standard physiological superfusion media (pH 7.35), the intracellular pH of cultured cells measured with 2',7'-bis-carboxyethyl-carboxyfluorescein (BCECF) was 7.26 +/- 0.03, and was regulated by an amiloride-sensitive Na-H exchanger. The time-averaged free intracellular Ca2+ level of cultured adult rat myocytes measured with fura-2 at an extracellular Ca2+ level of 1 mM was 99.0 +/- 16.8 nM. Ouabain, Bay k 8644 or isoproterenol caused a significant rise in time-averaged intracellular [Ca2+], while the dihydropyridine Ca channel blocker nifedipine induced a decrease in intracellular [Ca2+]. Measurements of contractile state with an optical-video system demonstrated that ouabain. Bay k 8644, isoproterenol, or elevated extracellular [Ca2+] increased the amplitude of cell motion and the rates of both shortening and relaxation, while nifedipine lowered them. Microelectrode impalements indicated a resting potential of -75 +/- 1 mV and an action potential amplitude of 100 +/- 2 mV. Exposure of cultured adult rat cardiocytes to the thyroid hormone triiodothyronine (10 nM) for 48 hours resulted in a 2-fold increase in NaK-ATPase alpha-1 catalytic subunit mRNA accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Dysfunction of the monocyte-macrophage system in the idiopathic minimal change nephrotic syndrome.

We studied the function of phagocytes and the distribution of lymphocyte subpopulations in 23 patients with Idiopathic Minimal Change Nephrotic Syndrome. All the patients were in relapse at the time of the study. The latter was performed before specific therapy was started. Our control group consisted of 26 normal children who were studied while undergoing routine analysis prior to plastic surgery. Polymorphonuclear leukocytes from the patients showed no alterations in their ability to ingest and to kill candidas. On the contrary, peripheral blood monocytes had a normal phagocytic function with a decreased candidacidal activity when compared to normal controls (p less than 0.001). No correlation was found between serum immunoglobulin levels and the monocyte lytic function. The absolute number of B lymphocytes was significantly increased (p less than 0.05), whereas the absolute number of total lymphocytes, T lymphocytes and T4+ and T8+ cell subsets did not differ from those of the age-matched normal controls. Natural killer cells were functionally normal.

Child↗
PubMed1989

[The monocyte-macrophage system in Hodgkin's disease].

Hodgkin's disease (HD) is considered as a tumor of the lymph nodes histologically characterized by a variety of cell types, resembling a nonspecific inflammatory reaction. The Reed-Sternberg cells present in the granuloma are considered neoplastic due to cytogenetic alterations, tissue culture properties and heterotransplantability. They originate from a macrophage-derived interdigitating reticulum cell. The lymph node is an immunologic organ and its alterations reveal qualitative and/or quantitative defects of the immune system. These are observed in HD at very early stages even with a minimum of lymph node involvement. Considering HD as a neoplasm of the monocyte-macrophage system, our objective was to investigate the functional capability of peripheral blood monocytes transformed into macrophages in vitro. The phagocytic and lytic activities were evaluated by the generation of toxic oxygen metabolites as due to an excessive production of PGE-2. This defect could be corrected by cyclo-oxygenase inhibitors. The defect was present at very early stages of HD and persisted even during prolonged continuous complete remissions. We also found a defect in the ingestion of candida which could not be modified by drug treatment, indicating the existence of a global dysfunction of the phagocyte. Presently, more than 90% of HD patients respond to specific therapy and remain in prolonged remission, being considered "cured". This fact may contribute to the diminished number of reports in relation to the biology of the monocyte-macrophage system in this disease.

Arachidonic Acids↗
PubMed1989

[Immunologic studies in thalassemia major].

It is accepted that the immune alterations in patients with thalassemia major (TM) are secondary to the continuous transfusion-related antigenic stimulation together with iron overload. We evaluated the immune status of TM patients and found quantitative alterations in the distribution of peripheral blood lymphocyte subpopulations as well as functional alterations in natural killer (NK) cytotoxicity, B-cell differentiation, T-cell immunoregulation and phagocyte functional activities. TM patients, 10 years old or younger, have a lymphocyte profile and phagocytic activity similar to normal controls. Non-splenectomized thalassemic patients, older than 10, present lymphocytosis due to an increase in B lymphocytes and with splenectomy the T-CD8+ lymphocytes increase. With respect to phagocytes, the capacity to ingest candida is preserved while the candidacidal activity and the generation of toxic oxygen metabolites during the respiratory burst are diminished, and are inversely proportional with age and serum ferritin concentration, that is, older in age and higher in iron overload, more profound are the phagocyte dysfunctions. The altered B-cell function, the dysfunction of T immunoregulatory cells and the defective NK activity observed in TM patients were independent of the age of the patients and they were observed even in children younger than 10 years old and in general are attributed to blood transfusions. Moreover, there are some alterations that thalassemic carriers can express such as a defect at the level of NK and at B-cell function regulations, suggesting a possible genetic origin. Although complex, TM constitutes a human model that allows the dissection of specific immune defects, involving multiple factors, and can provide a better comprehension of how this complex immunoregulatory system works.

Humans↗