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1.
Environ Microbiol ; 26(2): e16549, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38196372

ABSTRACT

Microplastics affect soil functions depending on drought conditions. However, how their combined effect influences soil fungi and their linkages with ecosystem functions is still unknown. To address this, we used rhizosphere soil from a previous experiment in which we employed microplastic fibres addition and drought in a factorial design, and evaluated their effects on soil fungal communities. Microplastics decreased soil fungal richness under well-watered conditions, likely linked to microplastics leaching toxic substances into the soil, and microplastic effects on root fineness. Under drought, by contrast, microplastics increased pathogen and total fungal richness, likely related to microplastic positive effects on soil properties, such as water holding capacity, porosity or aggregation. Soil fungal richness was the attribute most affected by microplastics and drought. Microplastics altered the relationships between soil fungi and ecosystem functions to the point that many of them flipped from positive to negative or disappeared. The combined effect of microplastics and drought on fungal richness mitigated their individual negative effect (antagonism), suggesting that changes in soil water conditions may alter the action mode of microplastics in soil. Microplastic leaching of harmful substances can be mitigated under drought, while the improvement of soil properties by microplastics may alleviate such drought conditions.


Subject(s)
Ecosystem , Mycobiome , Microplastics , Plastics , Soil , Droughts , Soil Microbiology , Water/analysis
2.
Sci Rep ; 7(1): 17756, 2017 12 19.
Article in English | MEDLINE | ID: mdl-29259319

ABSTRACT

Competition is a key process that determines plant community structure and dynamics, often mediated by nutrients and water availability. However, the role of soil microorganisms on plant competition, and the links between above- and belowground processes, are not well understood. Here we show that the effects of interspecific plant competition on plant performance are mediated by feedbacks between plants and soil bacterial communities. Each plant species selects a singular community of soil microorganisms in its rhizosphere with a specific species composition, abundance and activity. When two plant species interact, the resulting soil bacterial community matches that of the most competitive plant species, suggesting strong competitive interactions between soil bacterial communities as well. We propose a novel mechanism by which changes in belowground bacterial communities promoted by the most competitive plant species influence plant performance and competition outcome. These findings emphasise the strong links between plant and soil communities, paving the way to a better understanding of plant community dynamics and the effects of soil bacterial communities on ecosystem functioning and services.


Subject(s)
Bacteria/growth & development , Lycium , Maytenus , Microbial Consortia/physiology , Rhizosphere , Soil Microbiology , Lycium/growth & development , Lycium/microbiology , Maytenus/growth & development , Maytenus/microbiology
3.
Phys Rev Lett ; 110(23): 231601, 2013 Jun 07.
Article in English | MEDLINE | ID: mdl-25167481

ABSTRACT

We present a new supersymmetric AdS(6) solution of type IIB supergravity with SU(2) isometry. Through the AdS/CFT correspondence, this has potentially very interesting implications for 5D fixed point theories. This solution is the result of a non-Abelian T duality on the known supersymmetric AdS(6) solution of massive IIA. The SU(2) R symmetry is untouched, leading to sixteen supercharges and preserved supersymmetry.

4.
Scand J Immunol ; 76(1): 11-20, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22486186

ABSTRACT

Mast cells are abundant in the skin and other peripheral tissues, where they are one of the first immune cells to make contact with invading pathogens. As a result of pathogen recognition, mast cells can be activated and release different preformed and de novo-synthesized mediators. Sporothrix schenckii is the fungus that causes sporotrichosis, a worldwide-distributed subcutaneous mycosis considered as an important emerging health problem. It remains unknown whether or not mast cells are activated by S. schenckii. Here, we investigated the in vitro response of mast cells to conidia of S. schenckii and their in vivo involvement in sporotrichosis. Mast cells became activated after interaction with conidia, releasing early response cytokines as TNF-α and IL-6. Although histamine release was not significantly stimulated by S. schenckii, we determined that conidia potentiate histamine secretion induced by compound 48/80. Furthermore, functional depletion of peritoneal mast cells before S. schenckii infection significantly reduced the severity of cutaneous lesions of the sporotrichosis. These data demonstrate that mast cells are important contributors in the host response to S. schenckii infection, suggesting a role of these cells in the progress of clinical manifestations in sporotrichosis.


Subject(s)
Mast Cells/immunology , Sporothrix/immunology , Sporotrichosis/immunology , Animals , Cell Degranulation/immunology , Chi-Square Distribution , Histamine/analysis , Histamine/immunology , Interleukin-6/immunology , Male , Mast Cells/microbiology , Mast Cells/ultrastructure , Mice , Mice, Inbred BALB C , Microscopy, Electron, Scanning , Rats , Rats, Wistar , Spores, Fungal/immunology , Sporotrichosis/microbiology , Tumor Necrosis Factor-alpha/immunology , p-Methoxy-N-methylphenethylamine/pharmacology
5.
Bol. méd. Hosp. Infant. Méx ; 67(2): 128-132, March.-Apr. 2010. tab
Article in Spanish | LILACS | ID: lil-701012

ABSTRACT

Introducción. El ducto arterioso permeable (DAP) es la cardiopatía congénita más frecuente; afecta hasta el 80% de los recién nacidos pretérmino de extremado bajo peso al nacer (<1 000 g). Actualmente se considera un importante problema de salud pública. El objetivo de este trabajo es demostrar que es posible realizar cierre quirúrgico de DAP en pacientes prematuros, en un hospital de 2° nivel que cuente con un cirujano pediatra entrenado. Métodos. Se analizaron los antecedentes, evolución clínica y manejo quirúrgico de 31 pacientes con diagnóstico de DAP. Los criterios para cierre quirúrgico fueron: 1) fracaso al cierre farmacológico, 2) hipertensión pulmonar moderada a severa con flujo de izquierda a derecha, 3) ecocardiograma con conducto mayor de 1.5 mm y relación Qs/Qp mayor de 1.5:1, 4) más de 5 días de vida extrauterina con DAP-HS. El abordaje fue por toracotomía posterolateral izquierda con disección extrapleural y cierre del DAP con doble ligadura de seda 2-0. Resultados. Se estudiaron 31 pacientes, 19 masculinos y 12 femeninos. La edad varió entre 30 y 35 semanas de gestación; el peso osciló entre 1 y 1.5 kg. El ecocardiograma confirmó el diagnóstico en el 100% de los pacientes. Todos se operaron entre 7 y 10 días de vida extrauterina, 15 de ellos no recibieron tratamiento farmacológico por haber sido diagnosticados tardíamente, 12 por falla al tratamiento farmacológico y 4 hubo alguna contraindicación médica para cierre farmacológico (sepsis, Insuficiencia renal aguda y/o alteraciones de la coagulación). No hubo muertes a consecuencia de la cirugía; los pacientes que fallecieron (5) fue entre 15-20 días posteriores a la cirugía, por otros problemas agregados. Todos los pacientes que sobrevivieron (26 pacientes) pudieron extubarse en un periodo de 2-5 días después de la cirugía. Conclusiones. El cierre quirúrgico de DAP es factible de llevar a cabo en un hospital de 2° nivel, cuando las indicaciones para cierre farmacológico no son posibles. Es un procedimiento sencillo, con complicaciones mínimas, que puede realizarse en la misma Unidad de Cuidados Intensivos Neonatales (UCIN), como demuestran nuestros resultados, con nula mortalidad transoperatoria.


Background: Patent ductus arteriosus (PDA) is the most common congenital cardiac defect affecting 80% of very low birth weight preterm newborns (<1 000 g) and is considered an important public health issue. The aim was to demonstrate that it is possible to perform surgical closure of PDA on premature newborns in a second-level hospital. Methods: We analyzed backgrounds and clinical evolution of 31 surgically treated patients with PDA. Criteria for surgical closure were 1) pharmacological closure failure, 2) pulmonary hypertension with left to right shunt, 3) echocardiogram with ductal diameter >1.5 mm, and Qs/Qp ratio (>1.5:1. 4) at >5 days of extrauterine life. All patients were operated using left posterolateral thoracotomy with extrapleural dissection and ductus closure with a 2-0 double silk ligature. Results: We studied 31 patients: 19 males and 12 females. Age range was between 30 and 35 weeks of gestational age. Birth weight was between 1 and 1.5 kg. Echocardiogram was confirmatory in 100% of patients; 15 patients did not have pharmacological closure, 12 had pharmacological closure failure, and 4 had medical contraindication for pharmacological closure (sepsis, renal failure and coagulation disturbances). There was no surgical mortality. In patients who died (five patients), it was after 15 or 20 postoperative days and due to problems unrelated to the surgical procedure. Conclusions: Surgical closure of PDA is feasible to perform in a second-level hospital with minimal complications. This was demonstrated with our results in those patients in whom pharmacological closure failed or was not indicated.

6.
Arch. Fac. Med. Zaragoza ; 48(1): 8-15, mar. 2008. ilus, tab
Article in Spanish | IBECS | ID: ibc-74258

ABSTRACT

En los últimos años ha habido un creciente interés por los estudios genéticos en poblaciones latinoamericanas, principalmente con objetivos evolutivos y forenses. En este estudio se ha analizado la distribución de frecuencias de 15 sistemas genéticos STRs autonómicos y de la distribución haplotípica de 12 marcadores STR de cromosoma Y en muestras de los tres grupos étnicos principales de Ecuador (AU)


In the past few years, there has been an increasing interest in genetic studies of Latin-American populations, with evolutionary and forensic purposes. Ecuador’s population is mainly structured in three major ethnic groups: mestizos, Native Americans and Afro-Americans. It is a small country with huge ethnic richness. However, there are few studies about these populations, especially about native Americans and Afro-Americans. In this study the frequency distribution of 15 autosomal STRs, and the haplotipic distribution of 12 Y-STRs have been analysed in samples form the three principal ethnic groups from Ecuador (AU)


Subject(s)
Humans , Male , Female , Genetics/education , Genetics/history , Genetic Techniques/instrumentation , Genetic Markers/genetics , Genetic Markers/physiology , Genetics, Population/methods , Ecuador/epidemiology , Genetics/ethics , Genetics/standards , Genetics/trends , Genetic Markers/ethics , Models, Genetic
7.
Arch. Fac. Med. Zaragoza ; 48(1): 16-20, mar. 2008. tab
Article in Spanish | IBECS | ID: ibc-74259

ABSTRACT

La caracterización genética de las poblaciones iberoamericanas resulta trascendental desde el punto de vista antropológico pero también desde el punto de vista de las investigaciones forenses y de criminalística. Nicaragua es el país más grande de Iberoamérica, y a pesar de que también es el menos poblado, su población tiene carácter multiétnico, estando conformado por mestizos, blancos, negros y amerindios, En este estudio se han determinado las frecuencias génicas de 15 STRs autosómicos en una muestra de la población nicaragüenses(AU)


The genetic caracterization of the different Ibero-American populations is of great interest for anthropological purposes, but also for forensic and criminal investigations. Nicaragua is the biggest country in Ibero-America, and although it is the least populated country, its population is multiethnic, being composed of mestizos, white, black and amerindios, In this study, the genetic frequencies of 15 autosomal STRs have been determined in a sample of the Nicaraguan population(AU)


Subject(s)
Humans , Male , Female , Genetics/education , Genetics/history , Genetic Techniques/instrumentation , Genetic Markers/genetics , Genetic Markers/physiology , Genetics, Population/methods , Anthropology, Cultural/methods , Nicaragua/epidemiology
8.
Patol. apar. locomot. Fund. Mapfre Med ; 4(1): 39-43, ene.-mar. 2006. tab
Article in Es | IBECS | ID: ibc-054642

ABSTRACT

Se hace un estudio prospectivo de 2532 pacientes atendidos en el servicio de Ortopedia y Traumatología del Hospital Territorial Docente de Cárdenas en el período de tiempo comprendido entre enero del 1984 y Enero del 2004, por presentar fracturas de huesos tubulares largos asociado a daño arterial, correspondiente al grupo IIIC propuesto por Gustilo y Andersen . Predominaron los pacientes del sexo Masculino (73.1%), Raza Blanca (60.1%) y grupos de edades comprendidos entre 41 y 50 años (38%). Los traumas por alta energía (48.3%) fueron la causa etiológica de la lesión más frecuente. El medio estabilización de la fractura más utilizado fue la fijación externa (95.1%). Un 78.6% del total de la muestra presentó compresión, desgarro o sección de la pared vascular. Solo en el 7.5% de los casos hubo ligadura del vaso por considerar que la circulación colateral seria incapaz de mantener una oxigenación tisular adecuada. La evolución final fue favorable en el 76.4% de la totalidad de la muestra. Los resultados considerados malos se debieron variaciones en el proceso de consolidación del tejido óseo. La proporción de producción de la matriz y su degradación dependen directamente de la población celular. La isquemia e hipoxia subsiguiente originan una hipofunción celular que tardará en recuperarse proporcionalmente al tiempo de no-vascularización. Este será, junto a factores osmolares y ácido básicos las causas que afecten el fenómeno de osificación


We do a prospective study of 2532 patients assisted in our service of Orthopaedics in Cardenas Territorial Hospital in the period of time understood between January of the 1984 and January of the 2004. They present fractures of long tubular bones associated to arterial damage, corresponding to the group IIIC proposed by Gustilo and Andersen. The patients of the Masculine sex prevailed (73.1%), White race (60.1%) and groups of ages understood between 41 and 50 years (38%). The traumas for high energy (48.3%) were the etiologic cause of the most frequent lesion. We use the external fixation in 95.1% of cases. 78.6% of the total of the sample presented compression, laceration or section of the vascular wall. Alone in 7.5% of the cases there was bond of the glass to consider that the serious collateral circulation unable to maintain an appropriate cellular oxygenation. The final evolution was favourable in 76.4% of the entirety of the sample. The bad results were owed variations in the process of consolidation of the bony fabric. The proportion of production of the womb and their degradation depend directly on the cellular population. The isquemia and subsequent hipoxia originate a cellular hipofunción that will take in recovering proportionally at the time of no-vascularización. This will be, next to factors osmolares and basic acid the causes that affect the ossification


Subject(s)
Humans , Arteries/injuries , Leg Bones/injuries , Fractures, Open/complications , Leg Injuries/complications , Fracture Fixation , Pseudarthrosis/diagnosis , Prospective Studies
9.
An Esp Pediatr ; 52(2): 164-7, 2000 Feb.
Article in Spanish | MEDLINE | ID: mdl-11003883

ABSTRACT

Tuberous sclerosis is characterized by the potential for hamartomatous growth in multiple organs. Common manifestations are hypomelanotic spots, facial angiofibromas, subependymal hamartomas, cortical tubers, cardiac rhabdomyomas, retinal hamartomas, and so on. Seizures and mental retardation are frequent. It is an autosomal dominant disease but there is a high percentage of spontaneous mutations. Neonatal diagnosis is exceptional. We report a case of a female term newborn who presented partial motor seizures at the third day of life. Physical examination revealed only a disturbance of cardiac rhythm. Echocardiography showed ventricular intramural rhabdomyomas. Magnetic resonance imaging disclosed periventricular subependymal nodules and cortical tubers. A retinal hamartoma was found in the right eye. At the age of 1 month, hypomelanotic spots were evident on the back skin. The patient had infantile spasms, followed by poorly controlled partial complex seizures together with severe psychomotor retardation. Examination of both parents was normal. We discuss the uncommon diagnosis of tuberous sclerosis during the neonatal period, as well as the exceptional mode of presentation of our patient, with seizures in the early neonatal period, a phenomenon rarely reported in the literature.


Subject(s)
Seizures/etiology , Tuberous Sclerosis/complications , Female , Humans , Infant, Newborn
10.
J Agric Food Chem ; 48(7): 2713-6, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10898610

ABSTRACT

Ripe mango puree (Smith cultivar) was treated with fungal polysaccharidases containing pectinolytic, hemicellulolytic, and cellulolytic activities for 2 h at 50 degrees C. A loss of 30% of the cell wall material (CWM) was measured. CWM polysaccharides were hydrolyzed to varying degrees: 88, 65, and 65% of, respectively, galacturonic acid-, arabinose-, and rhamnose-containing polymers were hydrolyzed, whereas 50% of cellulose was degraded. After 30 min of treatment, the ethanol precipitation test on the serum was negative, indicating that pectic substances were rapidly hydrolyzed. Oligogalacturonic acids (degree of polymerization, 1-12) were observed in the serum. A viscosity drop of 90% was measured after 2 h, confirming the dominant role of pectic substances in puree viscosity.


Subject(s)
Cell Wall/chemistry , Fruit/chemistry , Polysaccharides/chemistry , Glycoside Hydrolases/metabolism , Viscosity
11.
An. esp. pediatr. (Ed. impr) ; 52(2): 164-167, feb. 2000.
Article in Es | IBECS | ID: ibc-2408

ABSTRACT

La esclerosis tuberosa es un síndrome neurocutáneo caracterizado por el crecimiento de hamartomas en distintos órganos. Son hallazgos típicos: manchas cutáneas hipocrómicas, angiofibromas faciales, nódulos subependimarios, tubérculos corticales, rabdomiomas cardíacos, hamartomas retinianos, etc. Son frecuentes la epilepsia y el retraso psicomotor. La herencia es autosómica dominante, aunque muchos de los casos son esporádicos. Rara vez debutan en el período neonatal. Se describe un recién nacido a término, mujer, sin antecedentes de interés, que ingresa al tercer día de vida por presentar crisis convulsivas clónicas de miembros izquierdos. A la exploración física presenta una arritmia cardíaca con extrasístoles, siendo el resto normal. La ecocardiografía demostró la presencia de rabdomiomas. La resonancia magnética cerebral evidenció túberes corticales y nódulos subependimarios. En el examen de fondo de ojo se encontró un hamartoma retiniano derecho. Al mes de vida eran ya evidentes máculas cutáneas acrómicas. En su evolución, la niña presentó espasmos infantiles y, posteriormente, crisis parciales complejas de difícil control farmacológico asociadas a un grave retraso psicomotor. El estudio de los padres fue normal. Queremos destacar la infrecuencia del diagnóstico de esclerosis tuberosa durante el período neonatal, así como el carácter excepcional del debut en nuestra paciente como crisis convulsivas en el período neonatal precoz, pocas veces referido en la literatura (AU)


Subject(s)
Child , Infant, Newborn , Female , Humans , Pediatrics , Physician's Role , Tobacco Use Disorder , Tobacco Smoke Pollution , Tuberous Sclerosis , Seizures
12.
J Agric Food Chem ; 48(12): 5995-6002, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11312772

ABSTRACT

Litchi (Litchi chinensis, Sapindaceae) is a nonclimacteric subtropical fruit that, once harvested, loses its red pericarp color because of browning reactions probably involving polyphenols. Low-pressure chromatography, high-pressure liquid chromatography, UV-visible spectral analysis, mass spectrometry, and nuclear magnetic resonance studies have allowed the determination and quantification of the polyphenolic composition of litchi pericarp. Litchi skins contain significant amounts of polyphenolic compounds. The principal characteristic of the litchi skin polyphenolic compounds is their ortho-diphenolic structure, which gives them high oxidability. Four major pigments were formally identified as cyanidin 3-rutinoside, cyanidin glucoside, quercetin 3-rutinoside (rutin), and quercetin glucoside. The tannin content was characterized after the depolymerization thiolysis reaction. Tannins (polymeric proanthocyanidins) are mainly constituted with epicatechin units linked by A- and B-type bonds. The different phenolic compounds of litchi cv. Kwai Mi were quantified by HPLC. Condensed tannins were the most abundant (4 mg x g(-1) of fresh skin), followed by epicatechin and procyanidin A2 (1.7 and 0.7 mg x g(-1) of fresh pericarp, respectively). The amount of anthocyanins was found to be comparable to that of flavonols, with a value of approximately 0.4 mg x g(-1) of fresh pericarp.


Subject(s)
Flavonoids/analysis , Fruit/chemistry , Phenol/analysis , Phenol/chemistry , Tannins/chemistry , Chromatography, Liquid , Flavonoids/chemistry , Flavonols , Magnetic Resonance Spectroscopy , Mass Spectrometry , Molecular Conformation , Molecular Structure , Tannins/analysis
14.
Enferm Intensiva ; 10(2): 51-7, 1999.
Article in Spanish | MEDLINE | ID: mdl-10763637

ABSTRACT

A study was made of the professional profile of nurses working in the intensive care or coronary units of the hospitals of the Community of Castilla-La Mancha, Spain. The study was based on a questionnaire completed by a significant sample of nurses working in these units. It synthesizes the most relevant concerns, expectations, and opinions of these nursing professionals on the basis of the results of the authors' analysis. Although most of the nursing professionals were satisfied with the care that they provide, there is demand for further training of nurses working in intensive care and coronary units. Ideas and questions about the future of nursing professionals in special intensive care and emergency units are discussed. The development of professional certification for special care is considered, which undoubtedly would contribute to meeting the demands of these professionals.


Subject(s)
Attitude of Health Personnel , Critical Care/standards , Nursing Staff, Hospital/education , Nursing Staff, Hospital/psychology , Professional Competence , Adult , Certification , Education, Nursing, Baccalaureate , Education, Nursing, Continuing , Educational Status , Health Knowledge, Attitudes, Practice , Hospitals, Community , Humans , Inservice Training , Intensive Care Units , Needs Assessment , Surveys and Questionnaires , Workforce
15.
Cancer Immunol Immunother ; 44(2): 97-102, 1997 Apr.
Article in English | MEDLINE | ID: mdl-9177471

ABSTRACT

The sterol 1alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] can inhibit T cell activation as well as restore the functional competence of suppressed T cells, The present studies determined whether 1,25(OH)2D3 had a differential effect on the activation of normal T cells or of suppressed T cells from mice bearing Lewis lung carcinoma tumors. Normal spleen cell proliferation in response to immobilized anti-CD3 was unaffected by the lower doses of 0.1-10 nM 1,25(OH)2D3, and was inhibited by the higher dose of 100 nM 1,25(OH)2D3. In contrast, 1,25(OH)2D3 increased proliferation and interferon gamma secretion by T cells of tumor bearers in response to stimulation through T cell receptor/CD3. Assessment of mechanisms associated with the 1,25(OH)2D3 stimulation of tumor-bearer T cells implicated protein phosphatase 2A (PP-2A). First, PP-2A activity of spleen cells from tumor bearers was reduced compared to that of normal spleen cells but was increased by 1,25(OH)2D3. Second, 1,25(OH)2D3 stimulation of tumor-bearer T cell proliferation was dependent on this PP-2A activity as it was blocked by doses of okadaic acid that selectively inhibit PP-2A. These results suggest that 1,25(OH)2D3 preferentially enhances the responsiveness of immunosuppressed T cells from tumor bearers to TCR/CD3 stimulation by restoring PP-2A activity.


Subject(s)
Calcitriol/pharmacology , Carcinoma, Lewis Lung/immunology , Lymphocyte Activation/drug effects , Phosphoprotein Phosphatases/metabolism , T-Lymphocytes/immunology , Animals , CD3 Complex/immunology , Carcinoma, Lewis Lung/enzymology , Cell Division/drug effects , Dose-Response Relationship, Drug , Enzyme-Linked Immunosorbent Assay , Interferon-gamma/drug effects , Interferon-gamma/metabolism , Lymph Nodes/enzymology , Lymph Nodes/immunology , Lymphocyte Activation/immunology , Mice , Mice, Inbred C57BL , Protein Phosphatase 2 , Receptors, Antigen, T-Cell/immunology , Spleen/enzymology , Spleen/immunology , T-Lymphocytes/metabolism , Tumor Cells, Cultured
16.
Clin Exp Metastasis ; 15(2): 102-10, 1997 Mar.
Article in English | MEDLINE | ID: mdl-9062386

ABSTRACT

The capacity of cloned metastatic Lewis lung carcinoma cells (LLC-LN7) to invade through reconstituted basement membrane-coated filters was reduced after incubation with 1alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3]. This was observed at doses as low as 10(-10) M 1,25(OH)2D3. The 1,25(OH)2D3-treated cells also had reduced levels of protein kinase A (PKA) activity and an increase in the level of polymerized actin, properties that have previously been demonstrated for less metastatic LLC variants. In addition, levels of the intermediate filament protein vimentin increased in 1,25(OH)2D3-treated LLC-LN7 tumor cells. In contrast, the levels and distribution of tubulin were not affected by 1,25(OH)2D3. The possibility that the decline in PKA activity was involved in the 1,25(OH)2D3 modulation of the cytoskeletal components was evaluated. To accomplish this, LLC-7 transfectants whose PKA levels were blocked due to expression of a mutated PKA R(1alpha) subunit (LN7-REV) were incubated with 1,25(OH)2D3 and their levels of F-actin were measured. In the absence of 1,25(OH)2D3 treatment, the PKA-defective LN7-REV cells had an increased level of polymerized actin as compared to the wild-type LLC-LN7 cells. This level of F-actin was minimally affected by 1,25(OH)2D3, suggesting that PKA activity is required for 1,25(OH)2D3 modulation of actin polymerization. These studies show that 1,25(OH)2D3 can reduce PKA activity in tumor cells, and that this reduction in PKA may be an intermediate signal through which 1,25(OH)2D3 affects the cytoskeleton and diminishes tumor invasiveness.


Subject(s)
Calcitriol/pharmacology , Carcinoma, Lewis Lung/enzymology , Carcinoma, Lewis Lung/secondary , Cyclic AMP-Dependent Protein Kinases/drug effects , Cytoskeleton/drug effects , Neoplasm Invasiveness/prevention & control , Animals , Carcinoma, Lewis Lung/pathology , Cell Movement/drug effects , Cyclic AMP-Dependent Protein Kinases/metabolism , Dose-Response Relationship, Drug , Mice , Phenotype , Vimentin/drug effects , Vimentin/metabolism
17.
Int J Cancer ; 74(1): 69-74, 1997 Feb 20.
Article in English | MEDLINE | ID: mdl-9036872

ABSTRACT

Human head and neck squamous cell carcinomas (HNSCC) that produce high levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) have been shown to contain CD34+ natural suppressor cells that inhibit the activity of intratumoral T-cells. The present study evaluated whether GM-CSF production and the presence of CD34+ cells within primary HNSCC would translate into increased recurrence, metastasis or cancer-related death during the 2 years following surgical excision. Freshly excised primary HNSCC of 20 patients that subsequently developed disease, and of 17 patients that remained with no evidence of disease were analyzed for production of GM-CSF and for CD34+ cell content. The cancers of patients that subsequently developed recurrences or metastatic disease produced almost 4-fold the levels of GM-CSF and had approximately 2.5-fold the number of CD34+ cells as did cancers of patients that remained disease-free. In a second method of analysis, the prognostic significance of high vs. low GM-CSF and CD34+ cell values was evaluated. These analyses showed that patients whose cancers produced high GM-CSF levels or had a high CD34+ cell content had a disproportionately high incidence of recurrence or metastatic disease (94% and 100%, respectively), while the majority of patients whose primary cancers produced low levels of GM-CSF or had a low CD34+ cell content remained disease-free (16% and 19%, respectively). Our results indicate that the presence of CD34+ cells in GM-CSF-producing HNSCC is associated with a poorer prognosis for the cancer patients and suggest the utility of these parameters as prognostic indicators of outcome. Mechanistically, our results suggest that the presence of immune suppressive CD34+ cells in GM-CSF-producing HNSCC leads to increased tumor recurrence or metastasis.


Subject(s)
Antigens, CD34/analysis , Antigens, CD/analysis , Biomarkers, Tumor/analysis , Carcinoma, Squamous Cell/pathology , Granulocyte-Macrophage Colony-Stimulating Factor/biosynthesis , Head and Neck Neoplasms/pathology , T-Lymphocytes, Regulatory/pathology , Adult , Aged , Carcinoma, Squamous Cell/immunology , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/physiopathology , Female , Follow-Up Studies , Granulocyte-Macrophage Colony-Stimulating Factor/analysis , Head and Neck Neoplasms/immunology , Head and Neck Neoplasms/mortality , Head and Neck Neoplasms/physiopathology , Humans , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Staging , Prognosis , Recurrence , Survival Rate , T-Lymphocytes, Regulatory/immunology , Time Factors
18.
Cancer Lett ; 111(1-2): 87-95, 1997 Jan 01.
Article in English | MEDLINE | ID: mdl-9022132

ABSTRACT

The role of protein phosphatase-2A (PP-2A) in regulating the motility and adhesion of human head and neck squamous cell carcinomas (HNSCC) was investigated. Immunofluorescent staining of these HNSCC cells showed PP-2A can co-localize with microtubules. That the PP-2A influences motility was shown by the increase in HNSCC cell migration through laminin and vitronectin when PP-2A was selectively inhibited with low dose okadaic acid, and by the reduction in invasion through these same matrix components by elevators of PP-2A activity. Motility of HNSCC cells through collagen I or fibronectin was not modulated by PP-2A. The reduction in HNSCC migration through vitronectin or laminin that resulted from treatment with PP-2A elevators was associated with an increase in cellular adhesiveness to these same ECM components. These studies show the association of PP-2A with the cellular cytoskeleton and its role in restricting the invasiveness of tumor cells through select extracellular matrix components.


Subject(s)
Carcinoma, Squamous Cell/metabolism , Head and Neck Neoplasms/metabolism , Head and Neck Neoplasms/pathology , Microtubules/metabolism , Neoplasm Proteins/metabolism , Phosphoprotein Phosphatases/metabolism , Calcitriol/pharmacology , Carcinoma, Squamous Cell/secondary , Ceramides/pharmacology , Humans , Neoplasm Invasiveness , Neoplasm Proteins/antagonists & inhibitors , Okadaic Acid/pharmacology , Phosphoprotein Phosphatases/antagonists & inhibitors , Protein Phosphatase 2 , Tumor Cells, Cultured/drug effects
20.
Cancer Lett ; 104(2): 153-61, 1996 Jul 12.
Article in English | MEDLINE | ID: mdl-8665483

ABSTRACT

By secreting granulocyte-macrophage colony-stimulating factor (GM-CSF), Lewis lung carcinoma tumors induce immune suppressive granulocyte-macrophage progenitor cells. Treating mice having established tumors and high levels of suppressor activity with vitamin D3 eliminated suppressor activity, increased anti-tumor immunity, induced an immune stimulatory cell population, and reduced tumor growth. When instead, the vitamin D3 treatment was initiated earlier, when implanted tumors first became detectable and when natural suppressor activity was less prominent, the treatment had no effect. Thus, vitamin D3 treatment can stimulate the immune competence of tumor bearers when treatment is targeted to coincide with a heightened presence of GM-CSF-induced suppressor cells.


Subject(s)
Adjuvants, Immunologic/pharmacology , Carcinoma, Lewis Lung/immunology , Cholecalciferol/pharmacology , T-Lymphocytes, Regulatory/physiology , Animals , Carcinoma, Lewis Lung/pathology , Cell Division/drug effects , Hematopoietic Stem Cells/physiology , Lymph Nodes/pathology , Mice , Mice, Inbred C57BL
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