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1.
J Dev Orig Health Dis ; 15: e8, 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38682547

ABSTRACT

Nearly 80% of the world's population trusts traditional medicine and plant-based drug compounds to improve health, and more than 50% of women who participated in a study have used herbal remedies during pregnancy. Bocconia frutescens L. is a plant native to tropical America, where infusion of its leaves has been widely used for the treatment of several gastrointestinal disorders. We have already shown that orogastric consumption of B. frutescens L. during the organogenesis period at concentrations equivalent to human consumption produces teratogenic effects in rats, but effects on progeny development have not yet been studied. In this study, we aimed to investigate the possible association between the consumption of B. frutescens L. at a dose equivalent to that consumed by humans and the neurological development of rat progeny. Pregnant Wistar rats were administered lyophilized B. frutescens L. extract at 300 mg/kg/day or vehicle via the orogastric route during the organogenesis period (gestation days 7-13). The physical development and sensory and motor maturation of their offspring during lactation were analyzed with a battery of reflex and physical tests. B. frutescens L. produced a significant delay in physical development and sensorimotor maturation, compared to the control group. Proton nuclear magnetic resonance spectroscopy analysis showed signals for both flavonoids and alkaloids in the B. frutescens L. extract. We conclude that the delay in physical and neurological development could be interpreted as alterations in the maturation of some neuronal circuitries induced by B. frutescens L.


Subject(s)
Plant Extracts , Prenatal Exposure Delayed Effects , Rats, Wistar , Animals , Female , Rats , Pregnancy , Plant Extracts/pharmacology , Male
3.
Hipertens Riesgo Vasc ; 38(3): e10-e12, 2021.
Article in Spanish | MEDLINE | ID: mdl-33715981

ABSTRACT

Liquorice is one of the oldest known herbs with medicinal properties and comprises up to 300 active compounds. It has been used for millennia for its digestive, anti-inflammatory and anti-infective properties. However, its possible toxic effects were described only a few years ago and there is growing interest in the side effects associated with chronic consumption. The main active component of liquorice is the prodrug glycyrrhizin and its active metabolite glycyrrhetic acid. It is a rare cause of hypokalaemia due to suppression of the renin-angiotensin-aldosterone axis, causing pseudohyperaldostenonism (PHA). We describe a rare case of secondary acute myocardial infarction in a patient with chronic consumption of liquorice.


Subject(s)
COVID-19 , Glycyrrhetinic Acid/adverse effects , Glycyrrhiza , Hypokalemia/chemically induced , Myocardial Infarction/chemically induced , Quarantine , Substance-Related Disorders/complications , Aged, 80 and over , Female , Humans , Severity of Illness Index
4.
J Dev Orig Health Dis ; : 1-4, 2020 Jan 07.
Article in English | MEDLINE | ID: mdl-31907091

ABSTRACT

It is estimated that 80% of the world population trusts traditional medicine. A large number of Americans use infusions of Bocconia frutescens L. leaves to treat cough and gastrointestinal disorders. However, phytochemical studies reveal that this plant contains alkaloids and other potentially harmful substances. This study aimed to evaluate the teratogenic effects of B. frutescens L. in an experimental model. Pregnant Wistar rats were administered lyophilized B. frutescens L. extract at 300 mg/kg/day or vehicle by orogastric route during the organogenesis period (gestation days 7-13), and external and internal congenital malformations were analyzed on the progeny on gestational day 20. Bocconia frutescens L. produced a significant increase in the number of different malformations, relative to the control group. We conclude that the consumption of B. frutescens L. during pregnancy at a dose equivalent to that consumed by humans increases the risk of teratogenic effects.

5.
Sci Rep ; 7: 40666, 2017 01 18.
Article in English | MEDLINE | ID: mdl-28098168

ABSTRACT

Mycobacterium tuberculosis (Mtb) causes nearly 10 millions of new tuberculosis disease cases annually. However, most individuals exposed to Mtb do not develop tuberculosis, suggesting the influence of a human genetic component. Here, we investigated the association of the rs2275913 SNP (G → A) from IL-17A and tuberculosis in Argentina by a case-control study. Furthermore, we evaluated in vitro the functional relevance of this SNP during the immune response of the host against Mtb and analyzed its impact on clinical parameters of the disease. We found an association between the AA genotype and tuberculosis resistance. Additionally, within the healthy donors population, AA cells stimulated with a Mtb lysate (Mtb-Ag) produced the highest amounts of IL-17A and IFN-γ, which further support the genetic evidence found. In contrast, within the tuberculosis patients population, AA Mtb-Ag stimulated cells showed the lowest immunological parameters and we evidenced an association between the AA genotype and clinical parameters of disease severity, such as severe radiological lesions and higher bacilli burden in sputum. Overall, our findings demonstrated that the AA genotype from the IL-17A rs2275913 SNP is positively associated with protection to active tuberculosis but related to higher disease severity in the Argentinean population.


Subject(s)
Alleles , Genetic Predisposition to Disease , Interleukin-17/genetics , Polymorphism, Single Nucleotide , Tuberculosis/genetics , Adult , Argentina , Female , Gene Frequency , Genotype , Humans , Interferon-gamma/blood , Interleukin-17/blood , Male , Middle Aged , Severity of Illness Index , Tuberculosis/diagnosis
6.
Rehabilitación (Madr., Ed. impr.) ; 47(3): 141-147, jul.-sept. 2013.
Article in Spanish | IBECS | ID: ibc-115450

ABSTRACT

Introducción. La recuperación de la capacidad funcional es un objetivo terapéutico primordial, proponiéndose el ejercicio como terapia coadyuvante, para combatir los efectos del decondicionamiento físico tras el trasplante de células precursoras hematopoyéticas (TPH). Presentamos nuestro estudio con el fin de exponer nuestra experiencia con el protocolo usado en nuestra unidad dentro del enfoque integral de los pacientes sometidos a TPH. Material y métodos. Estudio descriptivo prospectivo, incluyendo a todos aquellos pacientes sometidos a TPH, en el periodo comprendido entre enero de 2011 y julio de 2012, admitidos en el protocolo realizado en nuestro servicio. Revisamos y recopilamos los datos epidemiológicos, demográficos, características de su enfermedad, grado de actividad física y funcionalidad, en un total de 50 casos registrados en nuestra base de datos. Resultados. Edad media de 48,94 años (10-66). Síndrome mielodisplásico como causa más frecuente (30,4%). Todos los pacientes sometidos a trasplante presentaron una pérdida de fuerza, medida por un descenso global medio en el balance muscular de un punto; mientras solo el 24% precisaron tratamiento rehabilitador específico, porque presentaban signos de fragilidad funcional. Todos ellos recibieron recomendaciones respecto a la actividad física y normas higienicodietéticas. La distancia capaz de recorrer se vio considerablemente disminuida, con un 45% únicamente capaz de caminar 0-500 m, frente a un 60% capaz de caminar más de 2 km pretrasplante. No se objetivó aumento de fatiga postrasplante. Conclusiones. Todos los pacientes sometidos a TPH deben participar en un programa de rehabilitación, para prevenir las consecuencias de la inmovilidad y efectos adversos del tratamiento oncohematológico(AU)


Introduction. Recovering functional capacity is a fundamental therapeutic target. Exercise is proposed as an adjuvant therapy to combat the effects of loss of physical conditioning after Hematopoietic Stem Cell Transplantation (HSCT). We present our study in order to describe our experience with the protocol having a comprehensive approach to patients subjected to HSCT which is currently being used in our unit. Material and methods. A descriptive prospective study including all patients who had undergone HSCT, admitted in the protocol from January 2011 to July 2012, was carried out. The epidemiologic and demographic data as well as characteristics of the condition, physical activity level and functionality from 50 cases recorded in the database of our unit were collected and reviewed. Results. Mean age of the sample was 48.94 years (10-66). Myelodysplastic syndrome was the most common cause (30.4%). All patients who underwent transplant showed a loss of strength, measured by a mean global decrease of 1 point in muscle balance, although only 24% required specific rehabilitation treatment due to signs of functional frailty. All of them received recommendations regarding physical activity and hygiene and diet guidelines. The distance the subjects could cover decreased considerably, 45% only being able to walk approximately 0-500 m, while 60% had been able to walk more than 2 km prior to the transplant stage. No increase in fatigue was observed after the transplant. Conclusions. All patients who undergo HSCT should participate in a physical exercise program to prevent the effects of the lack of mobility and the adverse effects of the oncological and hematological treatment(AU)


Subject(s)
Humans , Male , Female , Middle Aged , Aged , Aged, 80 and over , Stem Cell Transplantation/methods , Gait/physiology , Gait Disorders, Neurologic/rehabilitation , Motor Activity/physiology , Granulocyte-Macrophage Progenitor Cells/transplantation , Transplantation, Homologous/methods , Transplantation, Homologous/rehabilitation , Receptors, Colony-Stimulating Factor/therapeutic use , Hematinics/therapeutic use , Gait Apraxia/rehabilitation , Prospective Studies , Physical Therapy Modalities
7.
Transplant Proc ; 42(6): 2383-6, 2010.
Article in English | MEDLINE | ID: mdl-20692486

ABSTRACT

INTRODUCTION: Early mortality in pediatric patients after liver transplantation (30 days) may be due to surgical and anesthetic perioperative factors. OBJECTIVE: To identify anesthetic risk factors associated with early mortality in pediatric patients who undergo liver transplantation (OLT). MATERIALS AND METHODS: This retrospective study of all patients who underwent a deceased or living donor liver transplantation evaluated demographic variables of age, weight, gender, degree of malnutrition, and etiology, as well as qualitative variables of anesthesia time, bleeding, massive transfusion, acid-base balance, electrolyte and metabolic disorders, as well as graft prereperfusion postreperfusion characteristics. Chi-square tests with corresponding odds ratio (OR) and 95% confidence intervals as well as Interactions were tested among significant variables using multivariate logistic regression models. P < or =.05 was considered significant. RESULTS: We performed 64 OLT among whom early death occurred in 20.3% (n = 13). There were deaths associated with malnutrition (84.6% vs 43.6%) in the control group (P < .01); massive bleeding, 76.9% (n = 10) versus 25.8% in the control group (P < .05) including transfusions in 84.6% (n = 11) versus 43.6% in the control group (P < .03); preperfusion metabolic acidosis in 84.6% (n = 11) versus 72.5% (n = 37; P < .05); posttransplant hyperglycemia in 69.2% (n = 9) versus 23.5% (n = 12; P < .01); and postreperfusion hyperlactatemia in 92.3% (n = 12) versus 68.6% (n = 35; P < .045). CONCLUSION: Prereperfusion metabolic acidosis, postreperfusion hyperlactatemia, and hyperglycemia were significantly more prevalent among patients who died early. However, these factors were exacerbated by malnutrition, bleeding, and massive transfusions. Postreperfusion hypokalemia and hypernatremia showed high but not significant frequencies in both groups.


Subject(s)
Anesthetics/adverse effects , Liver Transplantation/adverse effects , Acidosis/complications , Adolescent , Child , Child, Preschool , Hemorrhage/complications , Humans , Hyperglycemia/epidemiology , Hypokalemia/complications , Infant , Lactates/blood , Liver Transplantation/mortality , Odds Ratio , Perioperative Period/adverse effects , Retrospective Studies , Risk Factors , Transfusion Reaction
8.
Genes Immun ; 9(6): 546-55, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18650833

ABSTRACT

Using a multi-tiered, case-control association design, scanning 25 215 gene-centric SNPs, we previously identified two psoriasis susceptibility genes: IL12B and IL23R. These results have recently been confirmed. To better characterize the IL23R psoriasis-association, we used a fine mapping strategy to identify 59 additional IL23R-linked SNPs, which were genotyped in our three independent, white North American sample sets (>2800 individuals in toto). A sliding window of haplotype association demonstrates colocalization of psoriasis susceptibility effects within the boundaries of IL23R across all sample sets, thereby decreasing the likelihood that neighboring genes, particularly IL12RB2, are driving the association at this region. Additional haplotype work identified two 5-SNP haplotypes with strong protective effects, consistent across our three sample sets (OR(common)=0.67; P(comb)=4.32E-07). Importantly, heterogeneity of effect was extremely low between sample sets for these haplotypes (P(Het)=0.961). Together, these protective haplotypes attain a frequency of 16% in controls, declining to 11% in cases. The characterization of association patterns within IL23R to specific predisposing/protective variants will play an important role in the elucidation of psoriasis etiology and other related phenotypes. Further, this work is essential to lay the foundation for the role of IL23R genetics in response to pharmaceutical therapy and dosage.


Subject(s)
Genetic Predisposition to Disease , Psoriasis/genetics , Receptors, Interleukin/genetics , Case-Control Studies , Haplotypes , Humans , Idaho , Polymorphism, Single Nucleotide , Utah
9.
Genes Immun ; 9(2): 176-81, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18075513

ABSTRACT

A multitiered genetic association study of 25 215 single-nucleotide polymorphisms (SNPs) in three case-control sample sets (1446 patients and 1432 controls) identified three IL13-linked SNPs (rs1800925, rs20541 and rs848) associated with psoriasis. Although the susceptibility effects at these SNPs were modest (joint allelic odds ratios (ORs): 0.76 to 0.78; P(comb): 1.3E-03 to 2.50E-04), the association patterns were consistent across the sample sets, with the minor alleles being protective. Haplotype analyses identified one common, susceptible haplotype CCG (joint allelic OR=1.27; P(comb)=1.88E-04) and a less common, protective haplotype TTT (joint allelic OR=0.74; P(comb)=7.05E-04). In combination with the other known genetic risk factors, HLA-C, IL12B and IL23R, the variants reported here generate an 11-fold psoriasis-risk differential. Residing in the 5q31 cytokine gene cluster, IL13 encodes an important T-cell-derived cytokine that regulates cell-mediated immunity. These results provide the foundation for additional studies required to fully dissect the associations within this cytokine-rich genomic region, as polymorphisms in closely linked candidate genes, such as IRF1, IL5 or IL4, may be driving these results through linkage disequilibrium.


Subject(s)
Chromosomes, Human, Pair 5/immunology , Cytokines/genetics , Genetic Variation/immunology , Multigene Family/genetics , Psoriasis/genetics , Case-Control Studies , Haplotypes/immunology , Humans , Psoriasis/epidemiology , Psoriasis/immunology
10.
Rehabilitación (Madr., Ed. impr.) ; 38(5): 209-220, sept. 2004. tab, graf
Article in Es | IBECS | ID: ibc-35217

ABSTRACT

Introducción. Los objetivos del presente trabajo son conocer el perfil clínico de los pacientes que son sometidos a la sustitución protésica de rodilla, los factores hospitalarios y rehabilitadores implicados en la misma y su evolución a corto (alta de rehabilitación y año) y medio plazo (5 años).Pacientes y métodos. Se realizó un estudio prospectivo sobre 79 pacientes sometidos a implante protésico de rodilla en el período comprendido entre el 1 de enero de 1997 y el 31 de diciembre del mismo año. Se analizaron entre otras las siguientes variables: sexo, edad, media, antecedentes patológicos, clínica (dolor y función según la escala Knee Society Score [KSS]), estancia media y posquirúrgica, componentes protésicos, complicaciones, tratamiento rehabilitador durante el ingreso y ambulatorio. Se valoraron los resultados al alta de rehabilitación, al año y a los 5 años, utilizando la escala KSS. Resultados. La muestra tenía una media de edad de 67 años y predominio del sexo femenino (3:1) y de pacientes provenientes del medio rural (3:1). Entre los antecedentes patológicos con posible influencia en el implante destacaron la obesidad y la espondiloartrosis. El diagnóstico más frecuente fue la gonartrosis (75,9 por ciento), seguido de los procesos secundarios a reumatismos inflamatorios (15,2 por ciento). La puntuación media previa a la intervención para el dolor fue 11,9 y para la función 46,5. La estancia media fue 13,6 días. Se detectaron complicaciones mayores en el 24 por ciento de los pacientes. Durante su ingreso los pacientes recibieron una media de 4,8 sesiones de tratamiento rehabilitador (mediana: 6). Continuaron tratamiento rehabilitador al alta de forma inmediata el 82,3 por ciento de la serie, con un promedio de 32 sesiones. Las puntuaciones medias al alta de rehabilitación, al año y 5 años fueron para el dolor 39,4/39,7/38,1; mientras que para la función fueron 57,3/69,3/65,6. En los 5 años de seguimiento fue reintervenido un 30 por ciento de los pacientes (7 recambios, 13 artroplastias en rodilla contralateral y 4 implantes de cadera).Conclusiones. El estudio muestra buenos resultados tras implante protésico y tratamiento rehabilitador constatables al alta de rehabilitación. Al año de la intervención prosigue la mejoría conseguida al alta del tratamiento en Rehabilitación, manteniéndose a los 5 años (AU)


Subject(s)
Female , Male , Humans , Arthroplasty, Replacement, Knee/rehabilitation , Treatment Outcome , Time Factors , Prospective Studies
11.
J Reprod Immunol ; 62(1-2): 139-49, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15288189

ABSTRACT

In the present work, we investigated the Th1 and Th2 cytokine patterns secreted by infiltrating endometrial lymphocytes from fertile women and from patients with recurrent spontaneous miscarriage (RSM). Moreover, we also analyzed the expression of cytokines in the whole endometrium from fertile and RSM women. Furthermore, we investigated the expression of the activation marker signaling lymphocytic activation molecule (SLAM) a cell surface glycoprotein expressed on lymphocytes that upon engagement boosts IFN-gamma production. Our results showed a slight increase in IL-10 expression in the endometrium of some fertile women, although no significant differences were found in IFN-gamma and IL-5 expression. In contrast, analysis of IFN-gamma production by polyclonal activated lymphocytes from endometrium and/or peripheral blood from fertile women showed a significant increase compared to RSM. Analysis of SLAM protein expression in luteal phase endometrial samples showed a significant increase in the levels of the receptor in RSM women compared to fertile women. These results correlated with a significant augmentation of SLAM levels in peripheral blood T-lymphocytes from RSM patients. Interestingly, after treatment of RSM patients with paternal mononuclear cells, surface-SLAM-expression in T-cells from RSM patients significantly decreased up to levels comparable to those of fertile women. Taken together, our results suggest that endometrial cells have not a defined pattern-cytokine-production under pre-implatatory conditions, and SLAM might be a potential marker for the diagnosis of RSM and an indicator useful to follow up the patient response to allogeneic immunotherapy.


Subject(s)
Abortion, Habitual/immunology , Glycoproteins/metabolism , Immunoglobulins/metabolism , T-Lymphocytes/immunology , Abortion, Habitual/diagnosis , Abortion, Habitual/therapy , Antigens, CD , Biomarkers/analysis , Biomarkers/metabolism , Cytokines/genetics , Cytokines/metabolism , Endometrium/chemistry , Endometrium/cytology , Endometrium/metabolism , Female , Glycoproteins/genetics , Humans , Immunoglobulins/genetics , Immunotherapy/methods , Pregnancy , RNA, Messenger/analysis , RNA, Messenger/metabolism , Receptor-CD3 Complex, Antigen, T-Cell/immunology , Receptors, Cell Surface , Signaling Lymphocytic Activation Molecule Family Member 1 , T-Lymphocytes/chemistry
12.
J Immunol ; 167(10): 5719-24, 2001 Nov 15.
Article in English | MEDLINE | ID: mdl-11698444

ABSTRACT

Induction of Th1 cytokines, those associated with cell-mediated immunity, is critical for host defense against infection by intracellular pathogens, including mycobacteria. Signaling lymphocytic activation molecule (SLAM, CD150) is a transmembrane protein expressed on lymphocytes that promotes T cell proliferation and IFN-gamma production. The expression and role of SLAM in human infectious disease were investigated using leprosy as a model. We found that SLAM mRNA and protein were more strongly expressed in skin lesions of tuberculoid patients, those with measurable CMI to the pathogen, Mycobacterium leprae, compared with lepromatous patients, who have weak CMI against M. leprae. Peripheral blood T cells from tuberculoid patients showed a striking increase in the level of SLAM expression after stimulation with M. leprae, whereas the expression of SLAM on T cells from lepromatous patients show little change by M. leprae stimulation. Engagement of SLAM by an agonistic mAb up-regulated IFN-gamma production from tuberculoid patients and slightly increased the levels of IFN-gamma in lepromatous patients. In addition, IFN-gamma augmented SLAM expression on M. leprae-stimulated peripheral blood T cells from leprosy patients. Signaling through SLAM after IFN-gamma treatment of Ag-stimulated cells enhanced IFN-gamma production in lepromatous patients to the levels of tuberculoid patients. Our data suggest that the local release of IFN-gamma by M. leprae-activated T cells in tuberculoid leprosy lesions leads to up-regulation of SLAM expression. Ligation of SLAM augments IFN-gamma production in the local microenvironment, creating a positive feedback loop. Failure of T cells from lepromatous leprosy patients to produce IFN-gamma in response to M. leprae contributes to reduced expression of SLAM. Therefore, the activation of SLAM may promote the cell-mediated immune response to intracellular bacterial pathogens.


Subject(s)
Glycoproteins/biosynthesis , Immunoglobulins/biosynthesis , Interferon-gamma/biosynthesis , Leprosy/immunology , Th1 Cells/immunology , Antibodies/pharmacology , Antigens, Bacterial/immunology , Antigens, CD , Cells, Cultured , Cytokines/pharmacology , Glycoproteins/genetics , Humans , Immunoglobulins/genetics , Interferon-gamma/immunology , Interferon-gamma/physiology , Leprosy/genetics , Leprosy/pathology , Mycobacterium leprae/immunology , RNA, Messenger/biosynthesis , Receptors, Cell Surface , Signaling Lymphocytic Activation Molecule Family Member 1 , Up-Regulation
13.
FEMS Immunol Med Microbiol ; 29(2): 81-8, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11024345

ABSTRACT

The protection conferred by temperature-sensitive mutants of Salmonella enteritidis against different wild-type Salmonella serotypes was investigated. Oral immunization with the single temperature-sensitive mutant E/1/3 or with a temperature-sensitive thymine-requiring double mutant (E/1/3T) conferred: (i) significant protection against the homologous wild-type Salmonella strains; (ii) significant cross-protection toward high challenge doses of S. typhimurium. Significant antibody levels against homologous lipopolysaccharide and against homologous and heterologous protein antigens were detected in sera from immunized mice. Moreover, a wide range of protein antigens from different Salmonella O serotypes were recognized by sera from immunized animals. Besides, primed lymphocytes from E/1/3 immunized mice recognized Salmonella antigens from different serotypes. Taken together, these results indicate that temperature-sensitive mutants of S. enteritidis are good candidates for the construction of live vaccines against Salmonella.


Subject(s)
Salmonella Infections, Animal/prevention & control , Salmonella Vaccines/therapeutic use , Salmonella enteritidis/immunology , Animals , Antibodies, Bacterial/biosynthesis , Antigens, Bacterial/analysis , Blotting, Western , Lipopolysaccharides/analysis , Lymphocyte Activation , Mice , Mutation , Salmonella Infections, Animal/immunology , Salmonella enteritidis/genetics , Temperature , Vaccines, Attenuated/therapeutic use
14.
Rehabilitación (Madr., Ed. impr.) ; 34(5): 354-358, mayo 2000. ilus, tab
Article in Es | IBECS | ID: ibc-4885

ABSTRACT

En este trabajo hemos estudiado el resultado funcional de la fractura-luxación de codo una vez finalizado el tratamiento rehabilitador. Para ello, hemos realizado un estudio retrospectivo en el que se recogen 45 casos atendidos en los últimos 10 años, siendo la lesión más frecuente la luxación húmero-cubital posterior asociada a fractura de la cabeza radial. Hemos utilizado la escala de valoración de Morrey et al, por entender que tiene en cuenta aquellos factores que más pueden verse alterados en este tipo de lesión (dolor, movilidad, estabilidad y función).En nuestra muestra, los resultados finales aplicando esta escala han sido: excelente en 26 casos, bueno en 13, regular en cinco y malo solamente en un caso. Es importante reseñar que no buscamos tanto el arco de movimiento completo, que es difícil de conseguir, como el obtener un codo útil, es decir, válido para realizar de forma independiente las actividades de la vida diaria (AU)


Subject(s)
Adolescent , Adult , Aged , Female , Child, Preschool , Male , Middle Aged , Child , Humans , Elbow Joint/injuries , Joint Dislocations/rehabilitation , Fractures, Bone/rehabilitation , Recovery of Function , Retrospective Studies , Joint Dislocations , Treatment Outcome , Fractures, Bone
15.
J Immunol ; 162(10): 6114-21, 1999 May 15.
Article in English | MEDLINE | ID: mdl-10229854

ABSTRACT

We investigated the role of IL-18 in leprosy, a disease characterized by polar cytokine responses that correlate with clinical disease. In vivo, IL-18 mRNA expression was higher in lesions from resistant tuberculoid as compared with susceptible lepromatous patients, and, in vitro, monocytes produced IL-18 in response to Mycobacterium leprae. rIL-18 augmented M. leprae-induced IFN-gamma in tuberculoid patients, but not lepromatous patients, while IL-4 production was not induced by IL-18. Anti-IL-12 partially inhibited M. leprae-induced release of IFN-gamma in the presence of IL-18, suggesting a combined effect of IL-12 and IL-18 in promoting M. leprae-specific type 1 responses. IL-18 enhanced M. leprae-induced IFN-gamma production rapidly (24 h) by NK cells and in a more sustained manner (5 days) by T cells. Finally, IL-18 directly induced IFN-gamma production from mycobacteria-reactive T cell clones. These results suggest that IL-18 induces type 1 cytokine responses in the host defense against intracellular infection.


Subject(s)
Cytokines/biosynthesis , Interleukin-18/pharmacology , Killer Cells, Natural/drug effects , Leprosy/immunology , T-Lymphocytes/drug effects , Dose-Response Relationship, Drug , Humans , Interferon-gamma/biosynthesis , Interleukin-12/immunology , Leprosy/pathology , Monocytes/immunology , Tuberculosis, Pulmonary/immunology
16.
Microbios ; 94(378): 95-102, 1998.
Article in English | MEDLINE | ID: mdl-9785488

ABSTRACT

The feasibility of constructing attenuated mutants of Staphylococcus aureus with two temperature-sensitive (ts) lesions for ultimate development of a live-attenuated strain was investigated. Temperature-sensitive S. aureus strain G/1/2, which grows well at 31 degrees C but does not replicate at 37 degrees C, was subjected to chemical mutagenesis. After two enrichment cycles, fifteen mutants able to grow at 25 degrees C but unable to grow at 31 degrees C, were identified. Growth curves with temperature shifts from 25 to 31 degrees C, and from 31 to 37 degrees C confirmed that these were mutants with two lesions (dts), each with a different cut-off temperature. The reversion frequency of mutant G/1/2 at 37 degrees C was 2 x 10(-6) whereas those of several dts mutants were much lower (dts7: 7 x 10(-9) and dts12: 1 x 10(-9)). There was no increase in ts mutation reversion rate in response to prolonged incubation at 37 degrees C. The data support the further development of these mutants for use as a stable attenuated vaccine.


Subject(s)
Bacterial Vaccines/genetics , Point Mutation/immunology , Staphylococcal Infections/prevention & control , Staphylococcus aureus/genetics , Animals , Bacterial Vaccines/immunology , Cattle , Hot Temperature , Nitroso Compounds/pharmacology , Phenotype , Sensitivity and Specificity , Staphylococcal Infections/immunology , Staphylococcus aureus/growth & development , Staphylococcus aureus/immunology , Vaccines, Attenuated/genetics , Vaccines, Attenuated/immunology
17.
J Immunol ; 160(9): 4322-9, 1998 May 01.
Article in English | MEDLINE | ID: mdl-9574535

ABSTRACT

Human gamma delta T cells have the ability to rapidly expand and produce IFN-gamma in response to nonpeptide Ags of microbial pathogens, in particular a class of compounds known as the prenyl phosphates. We investigated the ability of IL-15, a T cell growth factor, to modulate prenyl phosphate-induced gamma delta T cell proliferation and cytokine production. IL-15 significantly enhanced the expansion of gamma delta T cells in the peripheral blood after stimulation in vitro with isopentenyl pyrophosphate. Moreover, using gamma delta T cell clones, we determined that IL-15-induced T cell proliferation was dependent on the IL-2R beta chain but not the IL-2R alpha chain. We therefore studied the IL-15R alpha chain expression in human gamma delta T cells in the presence or absence of nonpeptide Ags. We found IL-15R alpha mRNA expression in IL-15-stimulated and Ag-stimulated human gamma delta T cells but not in resting gamma delta T cells. Although IL-15 itself had little effect on the production of IFN-gamma, IL-15 plus IL-12 acted synergistically to augment IFN-gamma production by gamma delta T cells. Moreover, we showed that this increase in IFN-gamma could be explained by the dual activation of STAT1 and STAT4 by IL-15 and IL-12, respectively. Taken together, these results suggest that IL-15 may contribute to activation of human gamma delta T cells in the immune response to microbial pathogens.


Subject(s)
Antigens, Bacterial/immunology , Interleukin-15/pharmacology , Lymphocyte Activation/drug effects , Receptors, Antigen, T-Cell, gamma-delta/immunology , T-Lymphocyte Subsets/immunology , Cell Division/drug effects , Cell Division/immunology , Clone Cells , Cytokines/immunology , Diphosphates/immunology , Humans , Interleukin-15/immunology , T-Lymphocyte Subsets/microbiology
18.
FEMS Immunol Med Microbiol ; 20(1): 21-7, 1998 Jan.
Article in English | MEDLINE | ID: mdl-9514572

ABSTRACT

Female mice were immunized by the intramammary route with live-attenuated Staphylococcus aureus according to different schedules and challenged with virulent S. aureus. Immunization in late pregnancy or early lactation induced a significant decrease (P <0.05) in the number of S. aureus CFU recovered from glands after the challenge and a significant increase (P <0.05) in the levels of milk and serum specific IgG and IgA antibodies. Mice immunized before pregnancy were not protected from S. aureus challenge. Immunization did not increase the number of somatic cells in milk when compared with control mice. Protection from S. aureus intramammary infection may be achieved if mice are locally immunized during late pregnancy or early lactation.


Subject(s)
Bacterial Vaccines , Mastitis/prevention & control , Pregnancy Complications, Infectious/prevention & control , Staphylococcal Infections/prevention & control , Staphylococcus aureus/immunology , Animals , Antibodies, Bacterial/analysis , Antibodies, Bacterial/blood , Bacterial Vaccines/administration & dosage , Bacterial Vaccines/immunology , Female , Immunization Schedule , Immunoglobulin A/analysis , Immunoglobulin A/blood , Immunoglobulin G/analysis , Immunoglobulin G/blood , Mammary Glands, Animal/immunology , Mammary Glands, Animal/microbiology , Mammary Glands, Animal/pathology , Mastitis/immunology , Mice , Milk/immunology , Pregnancy , Pregnancy Complications, Infectious/immunology , Staphylococcal Infections/immunology , Vaccination , Vaccines, Attenuated/administration & dosage , Vaccines, Attenuated/immunology
19.
J Immunol ; 159(3): 1328-35, 1997 Aug 01.
Article in English | MEDLINE | ID: mdl-9233629

ABSTRACT

TCR gamma delta T cells are considered important in the rapid immune response to intracellular infection. We investigated the early response of peripheral blood gamma delta T cells to the nonpeptide Ag isopentenyl pyrophosphate and to its synthetic analogue ethyl pyrophosphate. In healthy donors, an increase in the number of gamma delta T cells was detected as soon as 4 days after stimulation with the nonpeptide Ags. Single-cell analysis of cytokine production was performed by intracellular staining of IFN-gamma and IL-4. gamma delta T cells were found to rapidly expand and produce IFN-gamma in response to nonpeptide Ags. Furthermore, IL-12 augmented the IFN-gamma response. In contrast, gamma delta T cells from the majority of HIV+ donors did not expand or express IFN-gamma in response to nonpeptide Ags, even in the presence of IL-12. These findings indicate a role for nonpeptide-reactive gamma delta T cells in effective cell-mediated immunity for intracellular pathogens.


Subject(s)
Antigens, Bacterial/pharmacology , Cytokines/analysis , Hemiterpenes , Mycobacterium/immunology , Organophosphorus Compounds/immunology , Receptors, Antigen, T-Cell, gamma-delta/analysis , T-Lymphocyte Subsets/immunology , Cells, Cultured , Cytokines/biosynthesis , HIV Seropositivity/immunology , Humans , Interleukin-12/pharmacology , Kinetics , Lymphocyte Activation/drug effects , Organophosphorus Compounds/pharmacology , T-Lymphocyte Subsets/drug effects , T-Lymphocyte Subsets/metabolism
20.
FEMS Immunol Med Microbiol ; 9(1): 55-63, 1994 Jun.
Article in English | MEDLINE | ID: mdl-7920464

ABSTRACT

Immunization with live-attenuated Staphylococcus aureus induced measurable levels of specific IgG and IgA in the lungs, but the pulmonary clearance of S. aureus in immunized mice did not differ from that of control mice. Aerosol exposure of mice to Pseudomonas aeruginosa induced a significant recruitment of polymorphonuclear leukocytes (PMNL) to the lungs in both immunized and control mice, whereas S. aureus challenge did not. However, challenge with a mixture of P. aeruginosa-S. aureus or exposure to an aerosol of Escherichia coli lipopolysaccharide (LPS) before S. aureus challenge induced PMNL migration and a significant enhancement of pulmonary clearance of S. aureus in immunized mice. The presence of both antibodies and PMNL was required for enhancement of S. aureus pulmonary clearance.


Subject(s)
Antibodies, Bacterial/immunology , Granulocytes/immunology , Immunization , Lung/microbiology , Staphylococcus aureus/immunology , Administration, Intranasal , Animals , Cyclophosphamide/pharmacology , Enzyme-Linked Immunosorbent Assay , Granulocytes/drug effects , Granulocytes/metabolism , Lung/immunology , Lung/pathology , Mice , Pseudomonas aeruginosa/immunology , Pseudomonas aeruginosa/pathogenicity , Staphylococcus aureus/pathogenicity
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