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Biomedical subjects

M Domínguez

Publications and source records attributed to M Domínguez.

At least 19 recordsLinked to original sources
PubMed2005

Clonal plasma cells from monoclonal gammopathy of undetermined significance, multiple myeloma and plasma cell leukemia show different expression profiles of molecules involved in the interaction with the immunological bone marrow microenvironment.

The immunological bone marrow (BM) microenvironment plays a major role in controlling growth and survival of clonal plasma cells (PC); this might translate into different patterns of expression of molecules involved in immune responses on PC from different types of monoclonal gammopathies (MG). We have studied the expression of a group of nine such molecules on both BMPC and the plasma of 61 newly diagnosed MG patients (30 MG of undetermined significance (MGUS), 27 multiple myeloma (MM) and four plasma cell leukemia (PCL)) and five normal individuals. Clonal PC from all MG displayed significantly increased levels of CD56, CD86 and CD126, and decreased amounts of CD38 (P<0.001). Additionally, HLA-I and beta2-microglobulin were abnormally highly expressed in MGUS, while CD40 expression was decreased in MM and PCL (P<0.05). Interestingly, a progressive increase in the soluble levels of beta2-microglobulin was found from MGUS to MM and PCL patients (P=0.03). In contrast, all groups showed similar surface and soluble amounts of CD126, CD130 and CD95, except for increased soluble levels of CD95 observed in PCL. Overall, those phenotypic differences are consistent with increased antigen presentation and costimulatory capacities in MGUS, which progressively deteriorate in malignant MG (MM and PCL).

Aged↗
PubMed2003

Development of high-frequency true-linear generator for electrochemical purposes.

A new design for a true-linear generator suitable for electrochemical measures is presented. The main component of generation system is an MAX038 chip, a high-frequency relaxation-type oscillator. The design is completed with a digital interface for computer control and an output stage to make signal suitable for cyclic voltammetry experiments. A digital circuit is also included to obtain single sweep signals by isolating one period or a half-period from continuous original output. Performance of presented generator is tested up to 1 MV s(-1) obtaining good stability and linearity.

Journal Article↗
PubMed2002

BHV-1 DNA vaccination: effect of the adjuvant RN-205 on the modulation of the immune response in mice.

It is well documented that adjuvants improve the immune response generated by traditional viral vaccines, but less is known about the effects of adjuvants on the immune response elicited by DNA vaccines. In this study, we have investigated the use of RN-205 (immunomodulator containing a membrane rich in lipopolysaccharide from gram-negative bacteria) as an adjuvant and analyzed the humoral and cellular specific immune responses elicited by DNA vaccines based on the bovine herpesvirus-1 (BHV-1) glycoprotein D (gD). The comparison of the antibody response induced in mice by a mixture of the three different versions of DNA gD (membrane-anchored, secreted and cytosolic) formulated with or without RN-205 showed that the immunomodulator did not affect the total specific humoral response. The cellular immune response induced in mice immunized with vaccines plus RN-205 was higher than that obtained in mice vaccinated without RN-205, not only in the indexes of proliferation tests but in the number of IL-4 and gammaIFN secreting cells. When total spleen cells were marked with specific monoclonal antibodies against surface markers, a significant increase in the macrophage population of all the groups receiving RN-205 was observed. CD8 and CD4 positive cells were also increased but to a lesser extent. Our results indicate that the incorporation of RN-205 into DNA vaccines induces an increase of the cellular specific immune response in mice.

Adjuvants, Immunologic↗
PubMed2001

Leishmania immune adherence reaction in vertebrates.

In normal human blood, C3-opsonized Leishmania promastigotes immune adhere to erythrocytes, a mechanism believed to enhance their clearance from blood and phagocytosis. Given the potential importance of this reaction in host defence against infection, the promastigote-erythrocyte interaction was studied in blood of individuals from one avian and 12 mammalian genera; [111In]-labelled promastigotes were found to bind only to primate erythrocytes. Nevertheless, previous experiments coincubating platelets isolated from nonprimate mammals with C3-opsonized promastigotes led to promastigote-platelet adherence. To ascertain whether this is a natural mechanism in nonprimate Leishmania infection, normal blood from members of Leishmania animal models of interest, dog, guinea-pig, hamster, mouse and rabbit, was infected ex vivo with promastigotes. Within 1 min of blood contact, the promastigote surface was loaded with platelets, rapidly evolving into large aggregates. These results confirm the physiological nature of the reaction and demonstrate that promastigote-erythrocyte and promastigote-platelet binding are the first parasite-host cell encounters after Leishmania invasion of primates and nonprimate mammals, respectively. Leishmania immune adherence shares the characteristics of the nonanticipatory immune systems, and we consider it should be viewed as an innate vertebrate host effector mechanism.

Animals↗
PubMed2000

Bile acid secretion during rat liver carcinogenesis.

Retro-differentiation of liver parenchyma during neoplastic processes is characterized by the expression of tumor antigens, such as alpha-fetoprotein and the placental isoenzyme of glutathione-S-transferase (GST-P). To investigate whether this may also affect a typical liver function such as bile acid secretion was the aim of this work. Rat hepatocarcinogenesis was induced by diethylnitrosamine (i.p., 200 mg/Kg body weight at day 0) and promoted by two-thirds partial hepatectomy (at day 21) plus 2-acetamidofluorene administration (50 mg/Kg body weight, subcutaneously, twice a week from day 14 to day 35). In order to carry out planimetric measurements of neoplastic tissue after immunohistochemical staining, a novel monoclonal antibody (MAb 14.1.3) against GST-P with no cross-reactivity against the major liver isoform of GST (GST-H) was raised. Analysis of total biliary bile acid output using the 3alpha-hydroxysteroid dehydrogenase method indicated that a significant reduction (-26%) occurred during the formation of GST-P-positive foci (12 wk). This was restored to normal values during adenoma formation (16-20 wk), but decreased again during carcinoma transformation (32 wk). These changes were not parallel to that observed in bile flow, which was progressively but slightly decreased throughout the whole period under study. HPLC analysis of bile samples collected for 1 h at different time points during hepatocarcinogenesis revealed that in contrast to what happens during cholestatic disease, a continuous and progressive increase in the cholic acid-to-chenodeoxycholic acid ratio (from 4.4+/-0.5 in control animals to 15.1+/-1.9 in rats with hepatocellular carcinoma) occurs. A significant and transient increase at 16 wk (+120%) in the proportion of bile acids amidated with glycine as compared to those conjugated with taurine was also observed. These results indicate that the mechanisms accounting for the secretion of major bile acids are modified differently at various steps of rat liver tumor development.

2-Acetylaminofluorene↗
PubMed2000

Respiration studies of penicillin solid-state fermentation.

An earlier work showed that when the bagasse content (BC) of the solid medium was decreased within a wide range of values, penicillin production by solid-state fermentation was always increased. Respiration studies were performed to understand how BC controls the secondary metabolism in this culture system. CO2 production of solid cultures with different compositions was monitored. In cultures of series A, the initial moisture content was increased and this variation was compensated by decreasing the nutrient and BC of the medium. In series B the initial moisture content was increased while BC was decreased and the nutrient content increased. In addition, penicillin production and respiration was also studied in extreme media (dry and concentrated and humid and diluted), with high and low BC. Criteria for the interpretation of respiration kinetics of the idiophase were established for the first time in this work. For the cumulative form (total CO2/g dry matter vs t) as well as for derivative (CO2/g dm/h vs t) respiration kinetics, the CO2 production rate (Q(CO2)) was determined by calculating the slope of the cumulative curve. Results indicate that Q(CO2) of the tropho- and idiophases was directly related to the BC of the solid medium (and inversely related to penicillin yields). These conclusions were confirmed by analysis of the derivative form, the results of which indicate that a lower but stable metabolic activity is essential for obtaining high penicillin yields in solid-state fermentation (SSF). The results indicate that the derivative CO2 production kinetics proved to be a more precise and sensitive indicator of the culture metabolic activity during idiophase than the cumulative respiration kinetics.

Journal Article↗
PubMed2000

Vaccination against hepatitis B virus in cirrhotic patients on liver transplant waiting list.

Patients with cirrhosis may fail to respond to anti-hepatitis B vaccine. An adequate response would be especially interesting when patients are on a liver transplant waiting list. Posttransplantation de novo hepatitis B has been well documented. One possible source is the grafting of organs from hepatitis B surface antigen (HBsAg)-negative, antibody to HBsAg (anti-HBs)-positive, antibody to hepatitis B core antigen-positive donors. The achievement of high titers of anti-HBs could be protective in this setting. We studied prospectively the response rate to recombinant hepatitis B vaccine (3 40-microg doses administered at 0, 1, and 2 months) in 62 patients with end-stage liver disease awaiting liver transplantation. Twenty-two patients showed antibody response (44%). A further 3 doses were administered in 15 of 28 nonresponders and were effective in 9 patients. Thus, the response rate reached 62% (31 of 50 patients completing 1 or 2 vaccination schedules before liver transplantation). Classic hepatitis B vaccination studies of patients with cirrhosis yield lower response rates. Vaccination with this double-dose schedule should be considered in such patients before liver transplantation.

Adolescent↗
PubMed2000

[Self-training in needle-knife sphincterotomy].

AIM: To analyze our experience in self-training in needle-knife sphincterotomy and to estimate the number of procedures necessary to reach competence in this technique. METHOD: Retrospective analysis of the first 60 needle-knife sphincterotomies performed, paying attention to success rates, the need for one or two attempts and the incidence and severity of early complications. The results were analyzed and divided into 2-year periods. The training period was subsequently determined using a qualitative method which combines the three above-mentioned criteria and sets competence level at 90%. RESULTS: Of the 60 attempted needle-knife sphincterotomies (five in Billroth-II patients), 54 (90%) were completed. The procedure was required in 20% of all the sphincterotomies completed. Needle-knife sphincterotomy was completed at the first attempt in 39 (65%) patients and complications appeared in 13 (22%), three (5%) of which were serious but not fatal. Analysis of 2 year periods showed an almost 100% increase in the total number of needle-knife sphincterotomies completed and in those completed at the first attempt, as well as a reduction in the complication rate, which subsequently stabilized at below 15%. Forty needle-knife sphincterotomies were needed to reach competence level. CONCLUSION: Needle-knife sphincterotomy can be learned without training from an endoscopist with experience in this technique. Competence can be reached after 40 procedures. Nevertheless, we propose an alternative method to our own to achieve competence in less time and with fewer complications.

Clinical Competence↗
PubMed2000

[Evaluation of Nugent and Amsel criteria for the diagnosis of bacterial vaginosis].

BACKGROUND: Bacterial vaginosis (BV) is a common disease in reproductive-age women and is associated to important gynecologic and obstetric complications. AIM: To study the occurrence of BV in apparently healthy women attending family planning clinics, using Amsel and Nugent diagnostic criteria. MATERIAL AND METHODS: Two hundred thirty nine women consulting for symptoms associated to cervicovaginitis, were studied. A sample from the lateral walls of the vagina was obtained with a sterile swab for microscopic analysis, Gram stain and amine test. RESULTS: According to Amsel and Nugent criteria a 31.1% and 31.8% BV prevalence was observed. The sensitivity and specificity of Nugent criteria, compared with Amsel criteria were 83.3% and 92.1%, respectively. CONCLUSIONS: The high prevalence of BV found in this study suggests that this vaginal infection should be diagnosed with standardized methods. Nugent criteria are economic easy to perform and sensitive and we propose that they should be used in local health centers.

Chile↗
PubMed2000

[Presence of integrons and their relationships with the resistance to third generation cephalosporins among nosocomial isolates of Acinetobacter baumannii].

BACKGROUND: Acinetobacter baumannii is an important etiological agent causing nosocomial infections. High level of resistance for different kind of antimicrobials has been observed, including beta-lactam antibiotics. This feature, chromosomal or plasmid encoded, has been associated to integrons harbouring antibiotic resistance gene cassettes. AIMS: To investigate the presence of integrons among clinical isolates resistant to third generation cephalosporins (3GC). MATERIAL AND METHODS: One hundred A. baumannii strains isolated from several Chilean hospitals were included in this study. Minimal inhibitory concentrations (MIC) of 3GC by an agar dilution method were carried out. Integrons class 1, 2 and 3 were investigated by colony blot hybridisation and confirmed by PCR. RESULTS: High level of resistance to all assayed 3GC was observed. On the other hand, integrón class 2 was the most prevalent (77% of isolates) followed by integron class 1 (52%). Forty six percent of isolates hybridised with probes for both of them. However, no positive hybridisation was detected for integron class 3. CONCLUSIONS: Nevertheless, most isolates harboured one or both class of integron; there was no direct relationship between the presence of these genetic structures and the resistance to this kind of beta-lactam antibiotics.

Acinetobacter↗
PubMed2000

[Activity of imipenem and meropenem against strains of Acinetobacter baumannii isolated from various Chilean hospitals].

The activity of two carbapenem compounds, imipenem and meropenem, against 447 strains of Acinetobacter baumannii isolated between 1990 and 1998 in different Chilean hospitals was determined. MIC ranges, MIC(50) and MIC(90), were determined by an agar dilution method. Similar antibacterial activities were observed for both antibacterials; however, a slight increase in the MIC(50) of imipenem and meropenem, and in the MIC(90) of meropenem was found among strains isolated from 1997-1998. Although A. baumannii remains susceptible to these antibiotics, the MIC(50) and MIC(90) have increased in recent years.

Acinetobacter↗
PubMed1999

Immune adherence-mediated opsonophagocytosis: the mechanism of Leishmania infection.

To mimic the sandfly pool feeding process and characterize the cellular and biochemical events that occur during the early stages of promastigote-host interaction, we developed an ex vivo model of human blood infection with Leishmania promastigotes. Within 30 s of blood contact, Leishmania promastigotes bind natural anti-Leishmania antibodies, which then activate the classical complement pathway and opsonization by the third component of complement. The opsonized promastigotes undergo an immune adherence reaction and bind quantitatively to erythrocyte CR1 receptors; opsonized Leishmania amastigotes also bind to erythrocytes. Progression of infection implies promastigote transfer from erythrocytes to acceptor blood leukocytes. After 10 min of ex vivo infection, 25% of all leukocytes contain intracellular parasites, indicating that blood cells are the early targets for the invading promastigotes. We propose that adaptation to the immune adherence mechanism aids Leishmania survival, promoting rapid promastigote phagocytosis by leukocytes. This facilitates host colonization and may represent the parasite's earliest survival strategy. In light of this mechanism, it is unlikely that infection-blocking vaccines can be developed.

Animals↗
PubMed1999

Dual role for Hedgehog in the regulation of the proneural gene atonal during ommatidia development.

The differentiation of cells in the Drosophila eye is precisely coordinated in time and space. Each ommatidium is founded by a photoreceptor (R)8 cell and these founder cells are added in consecutive rows. Within a row, the nascent R8 cells appear in precise locations that lie out of register with the R8 cells in the previous row. The bHLH protein Atonal determines the development of the R8 cells. The expression of atonal is induced shortly before the selection of a new row of R8 cells and is initially detected in a stripe. Subsequently atonal expression resolves into regularly spaced clusters (proneural clusters) that prefigure the positions of the future R8 cells. The serial induction of atonal expression, and hence the increase in the number of rows of R8 cells, requires Hedgehog function. Here it is shown that, in addition to this role, Hedgehog signalling is also required to repress atonal expression between the nascent proneural clusters. This repression has not been previously described and appears to be critical for the positioning of Atonal proneural clusters and, therefore, the R8 cells. The two temporal responses to Hedgehog are due to direct stimulation of the responding cells by Hedgehog itself.

Animals↗
PubMed1999

Compartments and organising boundaries in the Drosophila eye: the role of the homeodomain Iroquois proteins.

The Drosophila eye is patterned by a dorsal-ventral organising centre mechanistically similar to those in the fly wing and the vertebrate limb bud. Here we show how this organising centre in the eye is initiated - the first event in retinal patterning. Early in development the eye primordium is divided into dorsal and ventral compartments. The dorsally expressed homeodomain Iroquois genes are true selector genes for the dorsal compartment; their expression is regulated by Hedgehog and Wingless. The organising centre is then induced at the interface between the Iroquois-expressing and non-expressing cells at the eye midline. It was previously thought that the eye develops by a mechanism distinct from that operating in other imaginal discs, but our work establishes the importance of lineage compartments in the eye and thus supports their global role as fundamental units of patterning.

Animals↗
PubMed1999

[Insular carcinoma of the thyroid].

We report 5 cases of insular carcinoma of the thyroid. Most patients were females (80%) with an age range of 28 to 75 years. Treatment consisted of total or near total thyroidectomy plus modified cervical lymph node dissection in cases with lymph node metastasis. This was followed by radioiodine therapy and external radiation therapy in patients with residual disease. None of the patients had distant metastasis. However, three patients with involvement of the perithyroid soft tissue died within 4 years of the diagnosis. The other two patients are alive without evidence of disease. This type of thyroid carcinoma has an aggresive clinical course with frequent extension to the adjacent soft tissue associated to poor outcomes.

Adult↗
PubMed1999

[Hürthle cell carcinoma of the thyroid. A 41 years experience].

BACKGROUND: Hürthle cells can be found in non malignant thyroidal diseases such as Basedow Graves and Hashimoto diseases. When Hürthle cells comprise more the 75% of cellularity, they become a neoplasm. There are malignant variants of these neoplasms, constituted by follicular and papillary Hürthle cell carcinomas. AIM: To report a 41 years experience with Hürthle cell carcinomas of the thyroid. MATERIAL AND METHODS: A retrospective review of all patients operated for a thyroid carcinoma and selection of those patients with Hürthle cell carcinoma of the thyroid. RESULTS: Twenty two patients (21 female, mean age 48 years old) with Hürthle cell carcinoma of the thyroid were selected. Total or near total thyroidectomy was the treatment of choice in 20 and 19 received 131I. Metastatic involvement of cervical lymph nodes was found in five patients and they underwent modified cervical lymph node dissection. During follow up, only one patient died of the disease. We did not find higher incidences of local recurrences, distant metastases or mortality rates, compared to well differentiated thyroid carcinomas. CONCLUSIONS: Hürthle cell carcinomas of the thyroid and well differentiated thyroid carcinomas have similar biological behaviors. Their treatment should be similar, including total or near total thyroidectomy plus modified cervical node dissection when there is lymph node involvement. Radioactive iodine therapy and suppressive levothyroxin therapy should follow.

Adenocarcinoma↗