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L Sen

Publications and source records attributed to L Sen.

At least 37 records · Page 2Linked to original sources
PubMed2000

[Hyperprolactinemia is a frequent finding in HIV infection but does not correlate with viral burden].

Although many authors have reported the finding of hyperprolactinemia during the course of HIV infection, the circumstances determining the rise of prolactin (PRL) concentrations in serum are poorly understood. To analyze the relationships between serum PRL and other clinical variables in HIV-infected patients, 46 HIV-infected patients and 17 seronegative controls were studied. Serum PRL concentrations were significantly higher in the HIV-infected group (p = 0.022). Furthermore, Serum PRL and serum IgG correlated positively (Rs = 0.42; p = 0.05, Spearman-Rank). On the contrary, serum PRL concentrations did not correlate with the plasmic viral burden (Rs 0.039; p = 0.841), Our data confirm that hyperprolactinemia is a frequent finding during the course of HIV infection, and that serum PRL are independent of viral replication kinetics. Considering that a positive correlation was found between serum PRL and immunoglobulins, it is possible that serum PRL might increase in response to non specific immunological activation, or even in response to immunological activation at the onset of infections.

Adult↗
PubMed2000

[Immunological properties of prolactin].

A profound bi-directional interaction exists between the hormone prolactin and the immune system. Even the name "hormone" seems to be inadequate, since prolactin is clearly a growth factor and in fact it functions as an immune co-mitogenic cytokine using autocrine, paracrine and obviously endocrine mechanisms. Prolactin (PRL) stimulates lymphocyte proliferation in response to antigen and mitogens. In addition, prolactin is locally secreted by immune cells, and the pituitary production of prolactin is partially under the control of pro-inflammatory cytokines. These reciprocal influences imply the presence of specific receptors for prolactin in many immune cells, such as lymphocytes and other accessory cells. The PRL-binding to its receptor stimulates the synthesis and secretion of lymphocyte cytokines. In addition, it is a growth factor essential for at least one lymphoid cell line. The PRL-corresponding mRNA has been demonstrated in the cytoplasm of mitogen-stimulated lymphocytes, and the secretion of PRL has been well documented in lymphoid cells. Moreover, PRL acts on NK cells to induce their differentiation to prolactin-activated killer cells (PAK cells) in a dose-dependent way (activation at physiological concentrations, and cytotoxicity inhibition at tenfold higher concentrations). PRL also shows a well known capacity to induce IFN-gamma and IL-2 synthesis, suggesting their participation in the genesis of Th1-responses. These PRL immunological properties strongly support PRL as a cytokine. PRL involvement in both the normal immune response and in many pathological conditions raises important considerations regarding potential diagnostic and therapeutic applications.

Animals↗
PubMed2000

Epidemiology of human ancylostomiasis among rural villagers in Nanlin County (Zhongzhou Village), Anhui Province, China: II. Seroepidemiological studies of the age relationships of serum antibody levels and infection status.

Anti-hookworm antibody serologic responses were measured in residents of an Anhui provincial Chinese village where Ancylostoma duodenale is the predominant hookworm. Antibody responses were measured against either soluble infective third-stage larval (L3) or adult antigens. Immunoglobulins of the IgG class, especially IgG4 correlated with both the prevalence and intensity of A. duodenale hookworm infections. In contrast, there was an inverse correlation with IgM, but no correlation with IgA or IgE. Circulating IgG4 antibody responses might serve as a surrogate marker for active A. duodenale hookworm infection.

Ancylostomiasis↗
PubMed1999

Experimental approaches to the development of a recombinant hookworm vaccine.

Hookworm infection is a major parasitic cause of morbidity in the developing nations of the tropics. Development of a genetically engineered vaccine would be a useful tool in the control of this infection in highly endemic areas. Recombinant polypeptides belonging to the Ancylostoma secreted protein (ASP)-1 family have shown promise for reducing hookworm burdens after larval challenge infections in mice. Typically, these polypeptides are expressed in Escherichia coli and administered as an alum precipitate. Vaccine protection is antibody dependent. It is anticipated that a cocktail of different recombinant hookworm antigens may be required in order to effectively prevent heavy hookworm infections and disease. The progress of this work has been hampered by the absence of both a convenient laboratory animal with which to study hookworm infections resembling human infection, as well as the lack of easy availability of native hookworm antigens. In addition, useful human serologic correlates of antihookworm immunity are still poorly defined.

Ancylostoma↗
PubMed1998

Electron and light microscopy of peritoneal cellular immune responses in mice vaccinated and challenged with third-stage infective hookworm (Ancylostoma caninum) larvae.

The role of peritoneal macrophages in a murine model of immunity to living hookworm third-stage larvae (L3) was investigated. Mice immunized orally with 500 L3 once every 2 weeks for three times were challenged intraperitoneally with 2000 L3 1 week after the final immunization. The challenged larvae were collected from the peritoneal cavity at intervals between 2 and 72 h and then examined by inverted light microscopy, scanning electron microscopy and transmission electron microscopy. Peritoneal cellular responses in non-immunized mice served as negative controls. The numbers of peritoneal macrophages in immunized mice were 6-7-fold higher than in non-immunized mice. In the peritoneal cavity of immunized mice, host macrophages adhered to the challenged L3 within 2 h and created a cocoon-like encasing which surrounded the parasite. Extensive damage to the L3 was observed which included swelling, collapse and deformation of the larval cuticle. Lysis and vacuolization of the parasite's internal structures were also observed. In contrast, no significant cellular adherence and damage were observed in L3 recovered from non-immunized mice. L3-specific antibody levels were also elevated in the peritoneum of immunized mice relative to non-immunized controls. These studies implicate macrophages as important effector cells in hookworm larval vaccine immunity.

Ancylostoma↗
PubMed1998

Prolactin levels in the cerebrospinal fluid of patients with HIV infection and AIDS.

The objective of this study was to assess the levels of prolactin (PRL) in cerebrospinal fluid (CSF) of HIV-infected patients with regard to nonHIV-infected patients, and to assess the levels of prolactin in the CSF of HIV-infected patients with and without neurological HIV-involvement. Seventeen HIV-infected patients with different degrees of immunological and neurological involvement were studied. A second group of six HIV-seronegative patients with varying clinical conditions requiring lumbar punctures were included as controls. CSF was collected from patients and controls. Patients were studied neurologically and neuropsychologically, and computed tomography of the brain were performed. They were staged according to CDC clinical classification for HIV infection, and on the basis of tomographic findings into one of five stages. An additional classification for neurological involvement in AIDS was used. CD4+ cell counts, CSF studies, serum-prolactin levels and CSF-prolactin levels were performed as principal laboratory tests. CSF PRL concentrations were significantly higher in the HIV-infected group (n = 17) than the nonHIV infected control group (n = 6) (mean +/- s.d.; 5.77 +/- 2.22 vs. 3.53 +/- 0.69 x 10(-6) g l-1, respectively; p = 0.009, Mann-Whitney U-test). Moreover, even CSF-PRL concentration was higher in HIV-infected patients without cognitive impairment (stage 0 of the clinical classification), (n = 12) in comparison with nonHIV infected controls (n = 6) (mean +/- s.d.; 5.51 +/- 2.31 vs. 3.53 +/- 0.69 x 10(-1) g l-1, respectively; p = 0.028, Mann-Whitney U-test). There was a good correlation between serum and CSF-PRL levels in HIV-infected patients when measured by the Spearman Rank Test (rs = 0.773; p = 0.005). PRL raised serum levels were found in 4 out of 13 patients (30.73%). We conclude that higher levels of CSF-PRL are more frequently found in HIV-infected patients in comparison to uninfected controls. High levels of circulating PRL were also found in HIV-infected patients corroborating results from other work. A good correlation coefficient was found between circulating and CSF-PRL levels in HIV-infected patients, suggesting that disruption of the blood-brain barrier might account for a possible pathogenic mechanism.

AIDS Dementia Complex↗
PubMed1998

Reliability of laboratory markers of HIV-1 infection in Argentinian infants at risk of perinatal infection.

Early and accurate diagnosis of HIV-1 infection in infants born to HIV-1-seropositive mothers is of great importance. Polymerase chain reaction (PCR), HIV culture, and p24 antigen detection assays were evaluated for their ability to detect the presence of HIV in 195 infants at risk of perinatal infection. Using the Centers for Disease Control and Prevention guidelines for assessing HIV infection status in children younger than 18 months, 70 infants (36%) were diagnosed as HIV-1 infected and 125 (64%) lacked virologic and clinical evidence of infection. PCR and HIV culture were the most sensitive laboratory markers, detecting 100% and 98% of positive samples, respectively, regardless of age at testing. HIV-1 p24 antigen assay was detected in 26 of 38 positive samples but not in negative samples. PCR was performed with three different sets of primers (SK38/SK39-SK19-gag, SK68/SK69-SK70-env, and SK150/SK431-SK102-gag). The sensitivity/specificity of the individual assays were for SK19, 96.1%/94.25%; SK70, 89.6%/100%; and SK102, 100%/100%. A sample was considered HIV-1 positive when two positive PCR results were obtained with two different pairs of primers, and negative if the sample was negative when three sets of primers were used. False-positive results were occasionally obtained with probe SK19 in six seroreverter infants before serologic status was known. This suggested that the infection was caused by nonreplicative strains or were false-positive results probably by nonspecific amplification due to cross-reaction with other microorganisms; contamination was discarded because there was no specific amplification with the other two primers. All the HIV-1-infected infants were correctly identified with PCR; all except one could be identified with coculture and only 68.4% were confirmed with p24 antigen assay. No seroreverter infant was misdiagnosed using the criteria selected.

Argentina↗
PubMed1998

Different Effects of Amiodarone and Quinidine on the Homogeneity of Myocardial Refractoriness in Patients With Intraventricular Conduction Delay.

BACKGROUND: Increases in QT and JT dispersion have been suggested as indicative of a proarrhythmic potential as a result of heterogeneity in myocardial refractoriness, the reduction of which by antiarrhythmic agents might be associated with a beneficial effect on the development of serious ventricular arrhythmias. METHODS: To test the hypothesis that amiodarone reduces the heter-ogeneity of ventricular refractoriness to a significantly greater extent than quinidine in patients with intraventricular conduction defects under treatment for ventricular arrhythmias, the corrected and uncorrected QT and JT intervals and dispersions from 12-lead surface electrocardiograms were determined in 120 patients with intraventricular conduction defects with cardiac arrhythmias before and during treatment with amiodarone (n = 60) and quinidine (n = 60). RESULTS: Amiodarone increased QT from 403 +/- 50 ms to 459 +/- 47 ms (P <.001), with a similar increase in the corrected QT interval (QTc) (P <.001). Amiodarone reduced QT dispersion by 40% (P <.001), whereas quinidine increased by 18% (P <.001). The net effects of both drugs were similar for OTc. Amiodarone, but not quinidine, reduced heart rate significantly; amiodarone had no effect on the QRS; but quinidine increased if (P <.001). Quinidine as well as amiodarone increased the JT and JTc intervals significantly, but the effect of quinidine was qualitatively less striking. Amiodarone decreased the JT dispersion by 33% (P <.001) and JTc dispersion by 37% (P <.001). On the other hand, quinidine increased the corresponding values for JT and JTc by 18% (P <.001) and 21% (P <.001), respectively. The overall data on QT and JT dispersion indicate an improvement in the homogeneity of myocardial refractoriness with amiodarone treatment and the converse with quinidine treatment; this observation is consistent with a lower proarrhythmic propensity and mortality with amiodarone than with quinidine. Quinidine increased the QRS interval more than amiodarone, and the data indicate that in patients with intraventricular conduction defects, the monitoring of the JT interval might more accurately reflect changes in myocardial repolarization. CONCLUSIONS: Amiodarone and quinidine both increased the corrected and uncorrected QT and JT intervals; amiodarone decreased and quinidine increased the dispersion of these intervals, and these results suggested an improvement in the homogeneity of myocardial refractoriness as a result of amiodarone treatment and the converse as a result of quinidine treatment. Quinidine increased the QTS interval more than amiodarone, and the data indicate that in patients with intraventricular conduction defects, the monitoring of the JT interval might more accurately reflect changes in myocardial repolarization.

Journal Article↗
PubMed1998

Electrophysiological effects of MS-551, a new class III agent: comparison with dl-sotalol in dogs.

MS-551 is a newly synthesized, nonspecific K+ channel blocker. To elucidate its electrophysiological and potential proarrhythmic effects relative to those of dl-sotalol in vivo, serial changes in ECGs, endocardial and epicardial monophasic action potential durations, and left and right ventricular pressures were measured simultaneously in pentobarbital-anesthetized open-chest dogs. Complete heart block was produced by the injection of 37% formaldehyde into the atrioventricular node. Intravenous administration of MS-551 produced prolongation of action potential duration at 90% repolarization time (APD90) immediately after the beginning of infusion and reached plateau at 10 min. MS-551 (1 mg/kg) caused 73 +/- 8% increase in APD90 and 28 +/- 5% increase in QTc at basic cycle length of 700 msec. The maximal prolongation of APD90 induced by 1 mg/kg MS-551 was 39% greater than that by the same dose of sotalol (P < .01). The dose-response curve of prolongation of ventricular effective refractory period produced by MS-551 was shifted significantly to the left compared with that induced by sotalol. The EC50 was 0.5 +/- 0.1 mg/kg and 1.2 +/- 0.2 mg/kg for MS-551 and sotalol, respectively (P < .05). When 0.5 mg/kg MS-551 doses were used, no ventricular arrhythmia was induced by stimulation at 200-msec basic cycle length. When 1.5 mg/kg sotalol was administered, 5 of 15 developed torsade de pointes, 2 of 15 developed ventricular fibrillation and 5 of 15 developed sustained ventricular tachycardia. The idioventricular rates and left ventricular pressures were reduced significantly by sotalol, not by MS-551. In conclusion, MS-551 is a potent class III antiarrhythmic agent that selectively prolongs repolarization in the ventricular myocardium and appears to be devoid of autonomic effects. Dose for dose, it is more potent in prolonging the APD90 and the right ventricular effective refractory period possibly with a lower tendency for the development of proarrhythmia in a canine heart-block model.

Action Potentials↗
PubMed1998

In acute lymphoblastic leukemia deletion of the tumor suppressor gene P16 is associated with abnormal interferon genes.

The putative tumor-suppressor gene p16 was mapped to human chromosome 9p21, close to the interferon alpha cluster. The frequency and association of gene alterations of p16, interferon alpha and interferon beta were investigated in a total of 39 Acute Lymphoblastic Leukemia (ALL) patients. Of these, 10 patients (25.6%) presented abnormalities of at least one of the three genes studied. In 32 ALL cases studies of the three genes could be accomplished. In 23 out of 32 ALL cases the 3 genes studied were normally preserved. In the remaining 9 ALL, p16 was affected in 8 cases by homozygous deletions. In 2 patients, p16 deletion was associated with homozygous deletions for interferon alpha and interferon beta genes and in 1 case with total deletion of interferon beta 1 gene and partial deletion of interferon alpha. In the remaining 5 cases, p16 was the only gene deleted with no alteration of type I interferon genes. These data indicate that p16 gene is deleted in a higher frequency than type I interferon genes in ALL. Moreover, within the ALL group with p16 gene deletion, 37.5% are associated with interferon deletions and in general, ALL with alpha and/or beta interferon gene deletions are associated with p16 deletions. Therefore, p16 gene deletion with preserved type I interferon genes in some ALL suggests that the absence of this cdk inhibitor may disturb the normal cell cycle and favor blast transformation.

Adolescent↗
PubMed1997

Intracoronary adenovirus-mediated transfer of immunosuppressive cytokine genes prolongs allograft survival.

BACKGROUND: Intracoronary transfer and expression of recombinant genes in the intact heart is now feasible. In the transplant setting, local modulation of host immune responses by a genetically modified allograft may offer an attractive alternative to systemic immunosuppression. METHODS: We tested the efficacy and in vivo effect of intracoronary transfer of two immunosuppressive cytokine genes. First-generation E1-deleted adenoviral vectors expressing the Epstein-Barr virus interleukin-10 (AdSvIL10) or human transforming growth factor--beta 1 (AdCMVTGF-beta) were used. Rabbit cardiac allografts were transduced during cold preservation by slow (1 ml/min) intracoronary infusion of 10(10) pfu/gm diluted viral vectors and then implanted heterotopically. Controls included E1-deleted adenovirus (Ad5dI434) and AdCMVLacZ. Beating allografts were collected on day 4 for analysis of gene transfer efficacy and distribution. Additional grafts were used for evaluation of alloreactivity (n = 34). RESULTS: Mean allograft viral uptake was 81% (up to 91%). Polymerase chain reactions and reverse transcription-polymerase chain reactions confirmed the presence and expression of both genes in the grafts. beta-Galactosidase staining in AdCMVLacZ-infected grafts demonstrated efficient gene expression, which was highest (100%) in subepicardial regions. More homogeneous transmyocardial distribution of the transgene (in 25% to 40% of cells) could be achieved by pulsatile slow delivery. Allograft survival was 6.9 +/- 0.9 days in controls (n = 12), 11.1 +/- 1.7 days in AdCMVTGF-beta-infected grafts (n = 11, p < 10(-4)), and 11.2 +/- 3 days in AdSvIL10-infected grafts (n = 11, p < 10(-4)). Histologic scores (blinded) showed significantly (p < 0.005) higher regression coefficients for rejection in controls compared with both cytokine-transduced groups. Perioperative administration of cyclosporine A (INN: ciclosporin) to recipients had no effect on survival of AdCMVTGF-beta-infected grafts but reduced survival of AdSvIL10-infected grafts. CONCLUSIONS: Intracoronary gene transfer of immunosuppressive cytokines to cardiac allografts is efficient and effectively prolongs graft survival. Vectors that would induce long-term expression of such genes may make this approach clinically applicable.

Adenoviridae↗
PubMed1997

Monocyte phagolysosomal fusion in children born to human immunodeficiency virus-infected mothers.

BACKGROUND: Previously we demonstrated that monocyte phagolysosomal fusion is impaired in chronic HIV infection in adult patients. METHODS: We studied the phagolysosomal fusion of peripheral blood monocytes from 45 children vertically infected with HIV, 38 noninfected infants born to HIV-positive mothers and 14 children born to HIV-seronegative women, by a cytomorphologic method in which acridine orange is used as a fusion marker. RESULTS: The mean percentages of phagolysosomal fusion +/-SD were 42 +/- 16.1 for HIV-positive children, 55.3 +/- 15.5 for HIV-negative infants born to HIV-infected mothers and 58.2 +/- 12.7 for normal controls. Monocyte phagolysosomal fusion of HIV-infected children was significantly decreased in comparison to noninfected and normal infants (P < 0.001), while there was no difference between the two latter groups. Phagolysosomal fusion impairment in HIV-infected infants inversely correlated with age (r = -0.4527; P < 0.002) and directly correlated with CD4+ T cell counts (r = 0.393; P = 0.03). Moreover, phagolysosomal fusion strongly correlated with clinical manifestations; this function was significantly impaired in moderately and severely symptomatic HIV-infected children with respect to those who remained asymptomatic or mildly symptomatic (P < 0.05). CONCLUSIONS: Our results suggest that monocyte function in HIV-infected children progressively deteriorates, closely related to the severity of the clinical symptoms.

CD4 Lymphocyte Count↗
PubMed1996

Recombinant human immunodeficiency virus type 1 (HIV-1) Tat protein inhibits phagolysosomal fusion in human peripheral blood monocytes.

The effect of recombinant HIV-1 Tat protein on different functions of peripheral blood monocytes, such as candidacidal activity and phagolysosomal fusion, was evaluated. HIV-1 Tat protein caused a significant impairment of phagolysosomal fusion at 100 ng/ml (p = 0.018). The inhibitory effect of Tat on phagolysosomal fusion was blocked by the addition of 1 microgram/ml monoclonal anti-Tat antibody. Candidacidal activity of peripheral monocytes was not altered by HIV-1 Tat protein at the concentration of 1 microgram/ml. These results indicate the HIV-1 Tat protein can affect the monocyte microbicidal mechanisms at the phagolysosomal fusion step with little or not effect upon the lytic activity.

Antimetabolites↗
PubMed1996

Acute effects of thyroid hormone on inward rectifier potassium channel currents in guinea pig ventricular myocytes.

Thyroid hormones play an important role in cardiac electrophysiology. However, the regulation of cardiac ionic channels by thyroid hormones is still unclear. To evaluate the acute effect of 3,3',5-triiode-L-thyronine (T3) on inward rectifier potassium channel (IK1) action potentials, whole-cell IK1 currents and steady-state single IK1 currents were recorded in guinea pig ventricular myocytes. Acute exposure of cells to T3 resulted in shortening of the action potential durations. This effect was initiated at 5-15 min and reached a stable plateau at 25 min. The amplitude of steady-state whole-cell IK1 was significantly increased by T3 at 1 nM to 1 microM concentration rage and with ED50 12 nM/liter. T3 (1 microM) increased IK1 by 68 +/- 7% at -40 mV and 52 +/- 9% at -100 mV. Similar effects were observed with triiodothyroacetic acid, an analogue of T3 that does not stimulate DNA transcription. The single IK1 open probability (Po) was increased 7 +/- 1% by 1 nM T3 (n = 9, P < 0.05) and 42 +/- 6% by 1 microM T3 at -40 mV (n = 18, P < 0.0001). However, the channel unit amplitude, time constants of open and fast-closed time were not changed. T3 shortened interburst duration at each membrane potential but did not change the burst behavior. To elucidate detailed mechanism, we assumed a three-state model (C1 <==> C2 <==> O) and calculated each rate constant. T3 significantly increased the rate constant, k+1, for the transition from the C1 to the C2 state at RP -40 mV (2.84 +/- 0.56 to 7.28 +/- 1.23 sec-1, P < 0.01), RP -20 mV (3.63 +/- 0.95 to 10.17 +/- 2.60 sec-1, P < 0.05) and RP (6.73 +/- 1.20 to 21.94 +/- 4.49 sec-1, P < 0.01). However, the other rate constants were not affected. These results demonstrate that T3 enhances IK1 with the increment in Po, which mainly results from shortening of interburst duration without any changes in burst behavior. Hence, the shortening of interburst duration is due to acceleration of the transition from the C1 to the C2 state. The enhanced IK1 by T3 might be one of the causes for shortened action potential duration in hyperthyroidism.

Action Potentials↗
PubMed1996

Impaired monocyte function in patients successfully treated for Whipple's disease.

Peripheral blood mononuclear cells (monocytes) from patients with Whipple's disease in long-term remission were tested for their ability to handle intracellular microorganisms. Phagocytosis and lysis of Candida tropicalis by monocytes of patients (n = 12) and controls (n = 8) were quantified after 30 min of incubation. Phagocytosis was similar in both groups but intracellular killing of Candida tropicalis was significatively lower in patients (p < 0.001). We concluded that our study showed an in vitro defect in the intracellular killing function of monocytes in subjects in remission many years after diagnosis of Whipple's disease. The defective function did not seem to be related to relapse or to the susceptibility to other infections.

Aged↗
PubMed1995

Natural killer suppressor factors in sera from HIV-infected subjects.

We investigated the presence of NK suppressor factors in HIV+ sera. We further investigated if gp120 could be one of the substances responsible for the impairment of NKC regulation found in HIV+ asymptomatic patients. Our results indicate that HIV+ sera inhibit significantly normal NKC in a dose-dependent way, even at concentrations as low as 1%. The inhibitory effect of HIV+ sera decreased, but was not completely removed, by adsorptions of IgG or by treatment with a MoAb against human FcIgG. Pretreatment of normal effector cells with anti-CD16 MoAb slightly reduced their cytotoxic capability, but did not modify the suppressor effect of HIV+ sera. The The preincubation of normal PBMC with recombinant gp120 had also a suppressor effect even at 10 ng/ml. Pretreatment of HIV+ sera with anti-gp120 or anti-FcIgG MoAb reduced, but not completely, their inhibitory effect. In conclusion, HIV+ serum has a dose-dependent inhibitory effect on normal NKC. Most of this inhibition is caused by IgG, but other substances, such as gp120, can also contribute to it. Since the removal of IgG and further treatments of HIV+ sera were not able to abrogate completely the NK suppression, other serum factors still undetermined (TNF-alpha, other cytokines), should be considered.

Adult↗