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Biomedical subjects

A Pires

Publications and source records attributed to A Pires.

At least 19 recordsLinked to original sources
PubMed2006

Esophageal replacement in rat using porcine intestinal submucosa as a patch or a tube-shaped graft.

This study compares the efficacy of porcine intestinal submucosa (SIS) patch graft versus SIS-tube graft in esophageal replacement, using a novel esophageal regeneration model. Clinical function, as well as macroscopic and microscopic morphology were evaluated in both SIS-treated groups. We performed semi-circumferential esophageal excision followed by repair of the defect using either a SIS-patch graft (group I) or segmental esophageal excision followed by a SIS-tube interposition graft (group II) in rats. The 28-day survival rate was significantly different between the SIS-treated groups (100% in group I vs. 0% in group II). Unlike the rats in group II, which died within the first postoperative month due to esophageal dysfunction, all surviving animals in group I resumed a normal solid diet within a few days after surgery, without signs of esophageal dysfunction and gained weight. Barium swallow studies showed no evidence of fistula, significant stenosis or diverticula. No hematological or serum biochemistry abnormalities were found. By day 150 the SIS patch was replaced by esophageal-derived tissues. In the rat model, a patch graft technique using SIS appeared to induce esophageal regrowth and provided an initial and long-term satisfactory function, while a tube-shaped graft technique using SIS was unsuccessful.

Animals↗
PubMed2005

Mycobacterial immune reconstitution inflammatory syndrome in HIV-1 infection after antiretroviral therapy is associated with deregulated specific T-cell responses: beneficial effect of IL-2 and GM-CSF immunotherapy.

BACKGROUND: With the advent of antiretroviral therapy (ART) cases of immune reconstitution inflammatory syndrome (IRIS) have increasingly been reported. IRIS usually occurs in individuals with a rapidly rising CD4 T-cell count or percentage upon initiation of ART, who develop a deregulated immune response to infection with or without reactivation of opportunistic organisms. Here, we evaluated rises in absolute CD4 T-cells, and specific CD4 T-cell responses in 4 HIV-1+ individuals presenting with mycobacterial associated IRIS who received in conjunction with ART, IL-2 plus GM-CSF immunotherapy. METHODS: We assessed CD4 T-cell counts, HIV-1 RNA loads, phenotype for naïve and activation markers, and in vitro proliferative responses. Results were compared with those observed in 11 matched, successfully treated asymptomatic clinical progressors (CP) with no evidence of opportunistic infections, and uninfected controls. RESULTS: Median CD4 T-cell counts in IRIS patients rose from 22 cells/microl before initiation of ART, to 70 cells/microl after 8 months of therapy (median 6.5 fold increase). This coincided with IRIS diagnosis, lower levels of naïve CD4 T-cells, increased expression of immune activation markers, and weak CD4 T-cell responses. In contrast, CP had a median CD4 T-cell counts of 76 cells/microl at baseline, which rose to 249 cells/microl 6 months post ART, when strong T-cell responses were seen in > 80% of patients. Higher levels of expression of immune activation markers were seen in IRIS patients compared to CP and UC (IRIS > CP > UC). Immunotherapy with IL-2 and GM-CSF paralleled clinical recovery. CONCLUSION: These data suggest that mycobacterial IRIS is associated with inadequate immune reconstitution rather than vigorous specific T-cell responses, and concomitant administration of IL-2 and GM-CSF immunotherapy with effective ART may correct/augment T-cell immunity in such setting resulting in clinical benefit.

Journal Article↗
PubMed2004

Human herpes virus-8 serology and DNA analysis in recipients of renal allografts showing Kaposi's sarcoma and their respective donors.

Kaposi's sarcoma (KS) developed among 11 of 416 renal allograft recipients transplanted between 1985 and 2000. Only 3 among 364 Caucasian recipients developed KS, while it affected 8 of 52 Black patients, all of whom had been born in African countries (P <.001). All patients had their immunosuppression reduced; two also received daunorubicin and one received electrotherapy. Three patients developed accelerated renal allograft dysfunction, probably due to the reduced immunosuppression. Remission of KS was observed in seven patients, while lesions stabilized or improved partially in the other four. After resuming dialysis 2 of 11 patients died; both were in KS remission. Human herpes virus-8 (HHV-8) serology and DNA analysis was evaluated in sera obtained from seven donors: all were negative. Conversely, among eight sera collected pretransplant from the nine living recipients, HHV-8 IgG was detected in six and DNA was present in one. HHV-8 IgG was expressed in all patients (9/9) at some point posttransplant; DNA was detected in three patients. Therefore, the robust ethnic predisposition to KS was associated with a high pretransplant prevalence of HHV-8 among African recipients. Although some seroconversions were detected posttransplant, there was no evidence for donor-to-recipient transmission.

Base Sequence↗
PubMed2004

Treatment of primary HIV-1 infection with nonnucleoside reverse transcriptase inhibitor-based therapy is effective and well tolerated.

OBJECTIVES: Highly active antiretroviral therapy (HAART) has been advocated for the management of primary HIV-1 infection. We investigated the use of a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen in this setting. METHODS: Twenty-one antiretroviral-naïve individuals with early HIV-1 disease were treated with a combination of efavirenz and Combivir (GlaxoSmithKline, Uxbridge, Middlesex, UK). They were evaluated for immune and lymphocyte function by standard immunological assays. RESULTS: The median time to an undetectable HIV-1 viral load was 12 weeks (range 4-36 weeks). CD4 and CD16/56 counts increased during treatment and CD8 counts decreased minimally. The main side-effects observed were transient sleep disturbances (five patients). In addition, we observed a decrease in lymphocyte activation as assessed by CD38 surface expression. CONCLUSIONS: This study demonstrates that primary HIV-1 infection can be treated with NNRTI-based HAART.

Adult↗
PubMed2003

Reconstitution of CD4+ T cell responses in HIV-1 infected individuals initiating highly active antiretroviral therapy (HAART) is associated with renewed interleukin-2 production and responsiveness.

Reconstitution of functional CD4(+) T cell responsiveness to in vitro stimuli is associated with continuous highly active antiretroviral therapy (HAART). Thirty-six antiretroviral naive patients received HAART over 16 weeks. Antigen-specific, mitogen and interleukin (IL)-2 induced lymphocyte proliferative responses and specific IL-2 and IL-4 production were assessed at each time-point, together with quantification of HIV-1 RNA load and lymphocyte populations. Reconstitution of recall responses was limited largely to persistent antigens such as Herpes simplex virus and Candida, rather than to HIV-1 or neo-antigens. Recall antigens, mitogens and IL-2-induced renewed responses were associated with in-vitro production of IL-2, but not IL-4. Differential responsiveness to low versus high concentration IL-2 stimulus increases in a stepwise manner, suggesting normalization of IL-2 receptor expression and improved functionality. These increases in in-vitro proliferative responses thus probably reflect short lived effector clones, driven by ongoing antigenic stimulus associated with persisting long-term organisms. In this context non-responsiveness to HIV-1 antigens suggests ongoing HIV-1 specific clonal T cell anergy.

Anti-HIV Agents↗
PubMed2003

A pilot study of the safety and efficacy of thymosin alpha 1 in augmenting immune reconstitution in HIV-infected patients with low CD4 counts taking highly active antiretroviral therapy.

To study the safety and efficacy of thymosin alpha1 in stimulating immune reconstitution in combination with highly active antiretroviral therapy (HAART), a phase II randomized, controlled open-label trial of subcutaneous thymosin alpha1 was undertaken for 12 weeks. Twenty clinically stable patients with viral loads <400 copies/ml and CD4 counts less than 200 cells/microl were randomized to receive 3.2 mg thymosin alpha 1 subcutaneous injections twice weekly or no injections for 12 weeks. CD4 and CD8 counts, CD45 RO+ and RA+ subsets and signal joint T cell receptor excision circles (sjTREC) in peripheral blood mononuclear cells (PBMCs) were measured every 2 weeks. Thirteen patients received thymosin alpha 1 and seven were controls. Thymosin alpha 1 was well tolerated and there were no serious adverse events. There was no significant difference between the thymosin alpha1 and control groups in CD4, CD8 and CD45 lymphocyte subset changes at week 12; however, PBMC sjTREC levels increased significantly in the thymosin alpha 1-treated patients compared to controls at week 12. In conclusion, the increase in PBMC sjTREC levels in patients taking thymosin alpha1 may represent enhanced immune reconstitution; however, the clinical benefits and long-term consequences remain to be determined.

Adult↗
PubMed2002

Thymic activity in late-stage HIV-1 infected individuals receiving highly active antiretroviral therapy: potential effect of steroid therapy.

OBJECTIVE: Our objective was to monitor the effect of steroid therapy on the thymic output and function of late-stage HIV-1-infected patients undergoing highly active antiretroviral therapy (HAART). DESIGN: The indirect measurement of T cells that have recently emigrated from the thymus as a means of quantifying thymic output, and therefore thymic function, was achieved through use of the polymerase chain reaction-based signal joint T cell receptor rearrangement excision circles (sjTREC) assay. Proliferative capacity and interleukin (IL)-2 and IL-4 production by T cells after antigenic, mitogenic and IL-2 stimulation were also analysed. METHOD: Measurements were made of sjTREC levels in peripheral blood mononuclear cell DNA samples from five HIV-1 infected patients (one on steroid therapy prior to and at the time of sample extraction) receiving HAART. IL-2 and IL-4 production and proliferative capacity were also measured in three patients, including the patient receiving steroids. RESULT: The sjTREC assay gave an extremely weak result for the patient on steroids but, under the same assay conditions, provided clear, positive readings for the four patients not on steroids. Comparison of the patients' cytokine profiles revealed that IL-2 production was generally low or absent in all three patients tested but that IL-4 production was significantly higher in the patient given steroids. Functional potential as revealed by proliferation assays showed very low or absent cellular proliferation. CONCLUSION: The thymic contribution to the restoration of T lymphocyte numbers, particularly during the treatment of HIV-1 infection, may become compromised if thymic inhibitory factors such as steroids are used. Furthermore, the use of steroids may also favour the development of a T helper 2 response, which could prove particularly undesirable during HIV-1 infection.

Adult↗
PubMed2001

Immune responses and reconstitution in HIV-1 infected individuals: impact of anti-retroviral therapy, cytokines and therapeutic vaccination.

Most patients with chronic HIV-1 infection lack functional CD4(+) and CD8(+) HIV-1-specific T cells with proliferative and cytolytic capacity, respectively. This is despite being able to produce intracellular cytokines in response to viral antigens. Protease inhibitor (PI)-based highly active anti-retroviral therapy (HAART) is unable to completely eradicate virus and fails to enable total restoration of immunity including induction of anti-HIV-1 responses. We have taken novel approaches towards the treatment of chronic HIV-1 disease with the aim of instigating long-term non-progressor status and depletion of virus reservoirs. HIV-1-specific CD4(+) and CD8(+) T cell responses were measured following the administration of cytokines, during therapeutic vaccination, and following treatment interruption (TI) or drug therapy change. Administration of cytokines, with or without therapeutic vaccination, in HAART treated patients, improved both CD4(+) and CD8(+) HIV-1-specific T cell responses even in late-stage disease. Virus-specific T cell responses were also seen during TI or when transient viraemia was apparent, and following therapy change from a PI- to a non-nucleoside-based HAART regimen. Reconstitution of HIV-1-specific immune responses was found to be transient and reversal to the previous anergic state was rapid. Viral reservoirs in the latently infected resting CD4(+) T cells, on follicular dendritic cells of germinal centers or even in infected thymic epithelium may be involved in clonal suppression and anergy. These may present major obstacles to the maintenance of HIV-1-specific responses and the eventual eradication of HIV-1.

AIDS Vaccines↗
PubMed2001

Detection and quantification of HIV-1 specific CD4 helper and CD8 cytotoxic cells: their role in HIV-1-infected individuals and vaccine recipients.

There is a strong link between virus specific CD8 T-cell function and the efficiency of regulatory CD4 helper T cells. Controlling viraemia in HIV-1-infected individuals requires the maintenance of strong CD4 and CD8 T-cell responses. These responses should be elicited by prophylactic vaccination and by postexposure immunotherapy. This review will examine the methods that are available for the detection and quantification of HIV-1 specific CD4 and CD8 T-cell responses. We will also discuss the methods that should be used to identify these responses in HIV-1-infected individuals, seropositive recipients of immunotherapy and seronegative vaccinees. Finally, we will give examples of how responses observed in vitro relate to those known to occur in vivo.

AIDS Vaccines↗
PubMed2000

Catecholamines in larvae and juveniles of the prosobranch gastropod, Crepidula fornicata.

We investigated roles of catecholamines in metamorphosis of the prosobranch gastropod, Crepidula fornicata. Levels of DOPA, norepinephrine (NE) and dopamine (DA) were measured by high-pressure liquid chromatography (HPLC) in competent larvae and juvenile siblings that metamorphosed in response to the natural adult-derived cue or to elevated K+. Competent larvae contained 1.58 +/- 0.26 (S.E.M.) x 10(-2) pmol DOPA, 0.91 +/- 0.45 x 10(-2) pmol NE, and 0.290 +/- 0.087 pmol DA (mean values per microg total protein, n = 4 batches of larvae). Levels of DA per individual were not different between larvae and juvenile siblings; levels of NE were higher in juveniles. The tyrosine hydroxylase (TH) inhibitor alpha-methyl-DL-m-tyrosine (alpha-MMT) depleted DOPA and DA to approximately half of control values without affecting levels of NE. Depletion of DOPA and DA was accompanied by inhibition of metamorphosis in response to the natural cue but not to elevated K+. The dopamine-beta-hydroxylase inhibitor diethyldithiocarbamate (DDTC) induced high frequencies of metamorphosis at concentrations of 0.1-10 microM. In juveniles induced by 10 microM DDTC, levels of both NE and DA averaged approximately 80% of those in control larvae. Catecholamines may function as endogenous regulators of metamorphosis in C. fornicata.

Animals↗
PubMed2000

Correlation of genotypes and route of transmission with histologic activity and disease stage in chronic hepatitis C.

Our objective was to evaluate the histopathological features of chronic hepatitis C of 64 liver biopsies and to correlate this with the route of transmission of hepatitis C virus, the genotype of HCV, and the patient's age. Moderate chronic hepatitis was the most frequently observed (62.5%). Cirrhosis was observed in 14 patients (21.9%) and was more frequently found among patients over 40 years of age (34.3% vs. 6.9%, P = 0.025). The mean histopathological activity index (HAI) was significantly higher in the sporadic (10+/-3.1) than the posttransfusional (7.5+/-3.7) and the intravenous drug use (IVDU) groups (6.3+/-2.8) (P<0.02). Moreover the sporadic group showed more fibrosis (P<0.04) than the posttransfusional group. No liver cirrhosis was found in the IVDU group. The overall prevalence of HCV variants was: 54.7% type 1b, 4.6% type 1a, 37.5% type 2c, 1.6% type 2b, 1.6% type 2. The genotype distribution showed no relation to the HAI, hepatitis activity (grade), and fibrosis (stage) of the liver disease. In conclusion, the sporadic route of transmission of HCV was related to a more severe chronic hepatic disease, a finding that could influence future antiviral therapies. The predominance of HCV type 1b in this study reflects the higher frequency of this variant in our area. Our data suggests that the ultimate consequence of HCV chronic infection depends on patient age rather than on HCV genotype.

Adult↗
PubMed2000

Thromboangiitis obliterans: a rare cause of a reversible Raynaud's phenomenon.

A 25-year-old woman with progressive Raynaud's phenomenon and digital necrosis is presented. Systemic sclerosis and other connective tissue disorders as well as atherosclerosis and arterial emboli were excluded with appropriate laboratory examinations. Arteriography revealed multiple palmar and digital occlusions with corkscrew-shaped vessels. Based on these characteristic arteriographic and clinical findings, the diagnosis of thromboangiitis obliterans was finally retained. With intravenous perfusion of the prostacyclin analogue iloprost (2 ng/kg/min, 6 h daily during 21 days), a complete healing of Raynaud's phenomenon and of the digital necrosis was observed. There was no recurrence during the 1-year follow-up. This observation demonstrates that thromboangiitis obliterans is a potential reversible cause of severe Raynaud's phenomenon in young women even in the absence of lower limb involvement. Early recognition is important to avoid irreversible complications such as loss of digits.

Adult↗
PubMed2000

Catecholamines modulate metamorphosis in the opisthobranch gastropod Phestilla sibogae.

Larvae of the nudibranch Phestilla sibogae are induced to metamorphose by a factor from their adult prey, the coral Porites compressa. Levels of endogenous catecholamines increase 6 to 9 days after fertilization, when larvae become competent for metamorphosis. Six- to nine-day larvae, treated with the catecholamine precursor L-DOPA (0.01 mM for 0.5 h), were assayed for metamorphosis in response to coral inducer and for catecholamine content by high-performance liquid chromatography. L-DOPA treatment caused 20- to 50-fold increases in dopamine, with proportionally greater increases in younger larvae, so that L-DOPA-treated larvae of all ages contained similar levels of dopamine. A much smaller (about twofold) increase in norepinephrine occurred in all larvae. The treatment significantly potentiated the frequency of metamorphosis of 7- to 9-d larvae at low concentrations of inducer. In addition, L-DOPA treatment at 9 d increased aldehyde-induced fluorescence in cells that were also labeled in the controls, and revealed additional cells. However, all labeled cells were consistent with the locations of cells showing tyrosine-hydroxylase-like immunoreactivity. Catecholamines are likely to modulate metamorphosis in P. sibogae, but rising levels of catecholamines around the time of competence are insufficient alone to account for sensitivity to inducer in competent larvae.

Animals↗
PubMed1999

Shoe manufacturing and solvent exposure in northern Portugal.

Shoe manufacturing is a traditional industry in northern Portugal. There are nearly 1500 factories that employ about 54,000 workers. Among the materials used in the shoe manufacturing process, that could be occupational hazards, are the adhesives, especially adhesives solutions based on organic solvents. The National Institute of Health (Oporto Branch) carried out a study of 100 factories in northern Portugal to study solvent exposure in shoe manufacturing. The surveyed population, (4615 workers) was young (mean age = 33 years; range = 18-45) and predominantly female (68.5%). The results from the air samples analyses show 20 different organic compounds existing in the workplaces. The more common compounds found were n-hexane, toluene, and acetone. The results of the study show that in 53.7 percent of the factories there are operations where the solvent exposure is significant and represents a health hazard to the workers. These operations are mainly gluing, waxing, and polishing stations. Occupational risk of exposure to solvents concerned 44.2 percent of the workers. This study points out the existence of inadequate ventilation in the workplaces and inappropriate personal protective equipment to prevent dermatitis risk from adhesives, wax, and polish. The organic solvents present in workplaces also increase fire risk.

Adult↗
PubMed1997

Development of serotonin-like immunoreactivity in the embryos and larvae of nudibranch mollusks with emphasis on the structure and possible function of the apical sensory organ.

This investigation provides a light and electron microscopic examination of the development of serotonin-like immunoreactivity and structure of the apical sensory organ (ASO) in embryos and/or larvae of four nudibranch species: Berghia verrucicornis, Phestilla sibogae, Melibe leonina, and Tritonia diomedea. Serotonin-like immunoreactivity is first expressed in somata, dendrites, and axons of a group of five distinct neurons within the ASO. These neurons extend axons into an apical neuropil, a structure that is situated centrally and immediately dorsal to the cerebral commissure. Three of these neurons possess sensory dendrites that extend through the pretrochal epithelium, each supporting two cilia at their distal ends. Later development of serotonin-like immunoreactivity includes 1) axons from the apical neuropil that extend into each of the velar lobes; 2) neuron perikarya in the cerebral and pedal ganglia; 3) axons that extend through the cerebral commissure, cerebral-pedal connectives, pedal commissure, and possibly the visceral loop connective; and 4) axons extending from each pedal ganglion into the larval foot. Ultrastructurally, the ASO can be seen to be composed of three lobes and an apical neuropil that is separately delineated from the cerebral commissure. Four cell types are present within the ASO: ciliary tuft cells, type I and type II parampullary neurons, and ampullary neurons. Immunofluorescence and 3,3' diaminobenzidine tetrahydrochloride (DAB) labeling verify that the serotonergic neurons of the ASO are type I and type II parampullary neurons. The ampullary and type I parampullary neurons possess dendrites that extend through the pretrochal epithelium. These dendrites are partitioned into three bundles, one on either side of the ciliary tuft cells and a third bundle penetrating the pretrochal epithelium centrally between the ciliary tuft cells. One serotonergic type I parampullary neuron is associated with each of these bundles. Two ampullary neurons are associated with each of the lateral dendritic bundles, while the central bundle includes only one. Ultrastructural analyses of serotonergic axonal innervation arising from the ASO agree with those determined from fluorescently labeled material. The structure of the ASO and its associated serotonergic axons suggest that the serotonergic component of this structure senses environmental stimuli affecting velar function, possibly the contractility of muscle fibers in the velar lobes. Similarities and differences among the ASOs of embryos and larvae from various invertebrate phyla may provide useful data that will assist in the reconstruction of phylogenetic relationships.

Animals↗
PubMed1997

Catecholamines and dihydroxyphenylalanine in metamorphosing larvae of the nudibranch Phestilla sibogae Bergh (Gastropoda: Opisthobranchia).

The content of catecholamines and dihydroxyphenylalanine in larvae of the nudibranch Phestilla sibogae was analyzed by high-performance liquid chromatography with electrochemical detection. Dihydroxyphenylalanine, norepinephrine and dopamine were identified in larvae of all ages examined (5 through 12 days post-fertilization). Dihydroxyphenylalanine could be accurately quantified only in larvae of ages 8 through 12 days, when its average concentration increased from 0.62 to 6.71 x 10(-2) pmol micrograms protein-1. Between ages 5 and 12 days dopamine rose from 0.081 to 0.616 pmol microgram protein-1, and norepinephrine from 0.45 to 2.17 x 10(-2) pmol micrograms protein-1. Dihydroxyphenylalanine, dopamine and norepinephrine were also measured at different stages of metamorphic progress in 10- to 12-day larvae. Dihydroxyphenylalanine increased by a factor of 2.4 between the onset and completion of metamorphosis, but levels of dopamine and norepinephrine remained stable. One millimolar alpha-methyl-DL-m-tyrosine, an inhibitor of catecholamine synthesis, inhibited natural metamorphosis and depleted endogenous norepinephrine and especially dopamine, respectively, to 75% and 35% of control values. The existence of unexpectedly high levels of catecholamines in metamorphically competent larvae, and the association of catecholamine depletion with inhibition of metamorphosis, indicate that these compounds may participate in the control of gastropod development.

Animals↗
PubMed1992

Temperature coupling in cricket acoustic communication. I. Field and laboratory studies of temperature effects on calling song production and recognition in Gryllus firmus.

Temperature effects on calling song production and recognition were investigated in the North American field cricket, Gryllus firmus. Temporal parameters of field-recorded G. firmus calling song are strongly affected by temperature. Chirp rate and syllable rate increase, by factors of 4 and 2, respectively, as linear functions of temperature over the range in which these animals sing in the field (12 degrees-30 degrees C). Temperature affects syllable duration to a lesser extent, and does not influence calling song carrier frequency. Female phonotactic preference, measured on a spherical treadmill in the laboratory, also changes with temperature such that warmer females prefer songs with faster chirp and syllable rates. Best phonotaxis, measured as accuracy of orientation to the sound source, and highest walking velocity, occur in response to temperature-matched songs at 15 degrees, 21 degrees, and 30 degrees C. Experiments under semi-natural conditions in an outdoor arena revealed that females perform phonotaxis at temperatures as low as 13 degrees C. Taken together, the song and phonotaxis data demonstrate that this communication system is temperature coupled. A strategy is outlined by which temperature coupling may be exploited to test hypotheses about the organization of neural networks subserving song recognition.

Animal Communication↗