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M Gonzalez

Publications and source records attributed to M Gonzalez.

At least 37 records · Page 2Linked to original sources
PubMed2003

A simple and reliable pretreatment protocol facilitates fluorescent in situ hybridisation on tissue microarrays of paraffin wax embedded tumour samples.

AIMS: To describe a robust pretreatment protocol for preparing paraffin wax embedded tissues on tissue microarrays for fluorescence in situ hybridisation (FISH). The newly developed pretreatment protocol described here was compared with the commonly used sodium thiocyanate based protocol and two different heating methods used in standard antigen unmasking protocols for immunohistochemistry (pressure cooking and microwaving in citrate acid buffer). METHODS: Dewaxed tissue sections were incubated in 10mM citric acid buffer at 80 degrees C for 30 minutes to two hours, followed by a short pepsin digestion (1-5 mg/ml). Pretreated tissues were co-denatured with DNA probes at 80 degrees C for 10 minutes, followed by hybridisation at 37 degrees C for 48-72 hours. RESULTS: The three protocols using citrate acid buffer produced FISH signals with superior signal to noise ratios compared with sodium thiocyanate pretreatment. Most importantly, the best tissue attachment was achieved using the newly developed pretreatment protocol: on tissue microarrays less than 1% of cores were lost. To date, a total of 30 probes have been successfully hybridised on to breast tissue and multi-tissue microarrays. CONCLUSION: This pretreatment protocol is easy, reproducible, and facilitates FISH on tissue microarrays, with potential for widespread application in cancer research.

Breast Neoplasms↗
PubMed2002

Carney's syndrome: complex myxomas. Report of four cases and review of the literature.

Cardiac myxomas are rare tumors. They usually appear as a sporadic isolated condition in the left atrium of middle-aged women with no other coincidental pathology. Carney and others have described in young people a special complex group of cardiac myxomas associated to a distinctive complex pathology, giving identity to the "Syndrome Myxoma" or "Carney's Syndrome". Four additional cases of this syndrome, treated from 1977 to 1999 at the Hospital Clínico de la Universidad de Chile are presented here with a comprehensive review of the literature, accumulating 100 cases. The main features of our cases include the presence of malignant non cardiac tumors, a familial trend, follow-up of 23 years and an iterative recurrence in the elder case. To date all patients are tumor free. Reviewing the literature, patients with Carney's Syndrome were younger, with a mean age of 26 years and female predominance (62%). Cardiac myxomas affected the four chambers of the heart: 64% the left atrium; 44% the right atrium; 14% the left ventricle and 12% the right ventricle. They were multiple tumors in 41% and involved more than one chamber in 31%, being synchronous or metachronous. There was a marked familial trend (52%), a high incidence of recurrence (20%), with more than one occurring in half the cases. Extra-cardiac involvement consisted of: 68% pigmented skin lesions, 40% cutaneous myxomas, 37% adrenal cortical disease, 27% myxoid mammary fibroadenoma and 34% male patients with testes tumors. A low percentage had pituitary adenoma, melanotic schwannomas and thyroid disease. The diagnosis is made when two or more of these criteria are present. In agreement with these findings the four chambers of the heart should be examined at surgery for atypical myxoma locations, right atriotomy and combined superior-transseptal approach improve exposure of the cavities, careful screening of the first degree family members should be conducted, and closed short and long term follow up controls are important. Complex myxoma appears as a multi-systemic disorder, occasionally having an ominous prognosis and malignant potentiality, and is still undergoing investigation for better understanding and identification.

Adolescent↗
PubMed2002

Chimerism and minimal residual disease monitoring after reduced intensity conditioning (RIC) allogeneic transplantation.

Since graft-versus-leukemia (GVL) is the main weapon for disease eradication after reduced intensity conditioning (RIC) allogeneic SCT, the availability of sensitive and specific techniques to monitor changes in tumor load after transplant are especially helpful. These minimal residual disease techniques would allow an early intervention in the event of low tumor burden, for which immunotherapy is highly effective. Some authors have found an association between persistence of MRD, mixed chimerism and risk of relapse. Nevertheless, data from the literature remain contradictory and further correlations should be established, especially in RIC transplants. In this study we have analyzed the impact of MRD and chimerism monitoring on the outcome of 34 patients undergoing RIC allogeneic SCT who were considered poor candidates for conventional transplantation due to advanced age or other concurrent medical conditions. At day +100 25 (75%) patients reached complete remission (CR), there were five (15%) partial responses and three patients progressed. Incidence of grade 2-4 aGVHD and extensive cGVHD were 35% and 58%, respectively. Sixteen percent of patients developing aGVHD relapsed as compared to 47% in those without aGVHD (P = 0.03) and also 10% of patients developing cGVHD relapsed as compared to 50% relapses in those without cGHVD (P = 0.03). Four patients (12%) died due to early (n = 1) and late (n = 3) transplant-related mortality. After a median follow-up of 15 months, 24 out of the 34 patients remain alive. Projected overall survival and disease-free survival at 3 years are 68% and 63%, respectively. Early chimerism analysis showed 67% of patients with complete chimerism (CC) in bone marrow (BM), 86% in peripheral blood (PB), 89% in granulocytes and 68% in T lymphocytes. On day +100, these figures were 68%, 79%, 90% and 73%, respectively, and on day +180 there were 83% patients with CC in BM, 100% in PB, 100% in granulocytes and 100% in T lymphocytes. We observed a trend to a higher incidence of relapse in patients with mixed chimerism (MC) as compared to patients with CC. MRD monitoring by flow cytometry and/or RT-PCR analysis was performed in 23 patients. MRD assessment on days +21 to +56 after transplant allowed identification of patients at risk of relapse. In this sense, seven out of 12 patients (58.3%) who had positive MRD on days +21 to +56 relapsed as compared to none out of 11 patients who had negative MRD (P = 0.002). Of the seven patients with criteria to monitor MRD who relapsed after transplant, all but one remained MRD positive until relapse. By contrast, 10 patients remained MRD negative and all of them are in continuous CR. In nine additional patients, persistence of MRD or mixed chimerism was observed after transplant and withdrawal of cyclosporin with or without DLI was performed. Only two out of these nine patients relapsed. MRD clearance was preceded by CC and GVHD. In conclusion, in our study we found that RIC allogeneic transplantation can be used in patients considered poor candidates for conventional transplantation due to advanced age or other concurrent medical conditions with both low toxicity and low transplant-related mortality. Simultaneous studies of both chimerism and MRD are a useful tool in order to predict risk of relapse in patients undergoing RIC transplants and so can be helpful for individualizing treatment strategies after transplant.

Adult↗
PubMed2002

Determinants of cervical cancer screening in a poor area: results of a population-based survey in Rivas, Nicaragua.

OBJECTIVE: To obtain baseline information for designing a community-based intervention programme aimed at increasing the cervical cancer screening coverage of women most at risk. METHODS: A population-based survey, using proportional stratified two-stage cluster sampling in Rivas, one of the 16 Departments of Nicaragua. The individuals selected were interviewed at home by one of 26 interviewers, using a structured questionnaire. The questionnaire was designed to elicit (1) knowledge, attitudes and practices concerning sexual and reproductive health and behaviour, (2) risk factors for cervical cancer and (3) the use of health and cervical cancer screening services. RESULTS: A total of 612 men and 634 women participated in the survey. Of the women who had been sexually active at least 3 years, only 41.1% had undergone screening within that period and were considered adequately screened. Correlates of inadequate screening status included low educational level, exclusive use of public health facilities and lack of knowledge about prevention and symptoms of cervical cancer. Negligence, absence of medical problems, fear, lack of knowledge and economic reasons were the main reasons given for not being screened. Reluctance to be screened in the future was related to lack of knowledge of the disease, inadequate screening status, older age and low educational level. CONCLUSIONS: The current screening programme is not effective in reaching the majority of the population. Complementary activities such as education and information, as well as a more pro-active approach to invite women for screening are necessary.

Adolescent↗
PubMed2002

The importance of educational and psychological factors in Parkinson's disease quality of life.

OBJECTIVE: To define the factors correlated with quality of life (QoL) in patients with idiopathic Parkinson's disease (PD). BACKGROUND: PD has a substantial impact on QoL. Although several clinical factors have been associated with QoL in PD, the influence of patient's education still remains controversial. METHODOLOGY: A consecutive series of patients with PD were examined using the unified Parkinson's Disease Rating Scale (UPDRS part I, II, III), Schwab and England (SE), and Hoehn and Yahr stage (H&Y). QoL was rated with the PDQ-39, cognition with the Mini-Mental State examination (MMSE), and the presence of depressive symptoms with the geriatric depression scale (GDS). Patient's characteristics, estimated cumulative levodopa dose (CLD), UPDRS, H&Y, MMSE and GDS were correlated with the PDQ-39 using univariate and multiple regression analysis. RESULTS: A total of one hundred 58 patients (68 men, 90 women) with a mean age of 65.6 +/- 9.3 years, PD duration of 8.1 +/- 10.6 years, and education of 6.6 +/- 3.9 years were included. The mean PDQ-39 was 48.8 +/- 27.8, mean MMSE was 25.7 +/- 4, and mean GDS was 11.7 +/- 6.8. Using stepwise multiple regression analysis, the most important predictive factors were depression, UPDRS part I, UPDRS part II, and educational background, which accounted for a 61% of the variability of the PDQ-39 scores. CONCLUSIONS: In our PD sample, educational, behavioural, and psychological factors influenced life satisfaction more than physical ones.

Aged↗
PubMed2002

Prevalence and risk factors of sexually transmitted infections and cervical neoplasia in women's health clinics in Nicaragua.

OBJECTIVES: To determine prevalence and risk factors of sexually transmitted infections (STIs), HIV, and cervical neoplasia in women attending women's health clinics in Nicaragua, and to assess the potential impact of screening for these diseases. METHODS: Consecutive women attending women's health clinics in different regions were interviewed and examined for STI, HIV, and cervical neoplasia. RESULTS: Whereas only 30.4% of the 1185 participating women attended the clinics because of STI related complaints, 77.0% reported symptoms after probing. Clinical cervicitis was diagnosed in 32.8%, Chlamydia trachomatis in 4.1%, gonorrhoea in 0.4%, trichomoniasis in 10.2%. Antibodies for syphilis were found in 0.7%, for hepatitis B in 3.7%, and none were HIV seropositive. The STI prevalence was 21.8% in women offending with complaints, 17.3% in symptomatic women after probing, and 14.8% in asymptomatic women. Abnormal Papanicolaou (Pap) smears were found in 7.7%, with high risk human papilloma virus (HPV) types in almost 60%. Male promiscuity was associated with high grade squamous intraepithelial lesions (HSIL) and reported former screening was not shown to be protective. Young age and being employed were risk factors for C. trachomatis. CONCLUSION: Nearly one out of five women attending women's health clinics in Nicaragua had an STI, and one out of 13 a precancerous lesion of the cervix. These clinics provide an opportunity to improve the reproductive health of women by probing for STI symptoms, especially in young women, and by offering cervical screening to casual attendees. Of concern is the high rate of cervical lesions in women with a screening history, underlining the need for proper quality control.

Adolescent↗
PubMed2002

A biomechanical study of the finger pulley system during repair.

This paper addresses the mechanics of the finger/pulley system when subjected to various excisions and repairs. Several cadaver hands were used to study the finger/pulley's function, finger joint dynamics, and the relationship between tendon excursion and finger joint angles of rotation. By using a method of continuous and simultaneous data acquisition of the entire finger joint's motion, a more detailed analysis was achieved. Our experimental investigation is based on the use of four micro-potentiometers inserted at the finger's joints and a pulley system to simulate tendon excursion. Using this procedure, a detailed kinematic analysis of the entire finger was performed. This included analysis of the intact hand, various pulley excisions, and reconstruction. In addition to introducing a new method of acquisition, a mathematical model was developed for the inverse dynamic analysis of the finger pulley system. From this model, the torques required at the joints for the motion were computed. The results provided new insight into possible ways of characterizing kinematic changes resulting from pulley damage and repair.

Cadaver↗
PubMed2001

Deposition of atmospheric nitrogen compounds in humid tropical Cuba.

Acid deposition, a direct effect of gaseous air pollutants, is causing widespread damage to terrestrial and aquatic ecosystems. Further, these pollutants are responsible for the corrosion of building materials and cultural objects, as well as having an impact on human health. In Cuba, main atmospheric deposition of nitrogen compounds varies from approximately 12.0 to 65.0 kg N ha(-1) year(-1) in rural areas. Ammonia and ammonium are the most important elements in Cuba's tropical conditions.

Air Pollutants↗
PubMed2001

Detection of estrogen alpha and progesterone receptors and cell proliferation in the uterus during early pregnancy in the goat.

The objectives of this study were to investigate in the goat uterus the expression of estrogen-alpha (ER alpha) and progesterone receptors (PR) and their relationship to proliferation indices (Ki-67) during peri-implantation on Days 22 to 30 post coitum (pc). Immunohistochemical methods were used to quantify ER alpha and PR for luminal and deep regions of the endometrium and of the myometrium. On Day 22 pc cell proliferation was only observed in the luminal epithelium. On Day 24 pc, high cell proliferation indices were seen in luminal epithelium and proliferation began in the luminal stroma and glands. There was a positive correlation between Ki-67 and total ER alpha score in the luminal epithelium (r = 0.53, P < 0.01). Levels of PR scores were highly correlated with Ki-67 indices in luminal epithelium (r = 0.74, P < 0.01) and stroma (r = 0.70, P < 0.01). No Ki-67 expression was observed in deep glands, stroma or myometrium on any of the days studied. Results indicate that patterns of ER alpha and PR expression differ markedly, and that there was a high correlation between PR expression and cell proliferation in the caprine uterus during the peri-implantation period.

Animals↗
PubMed2001

The vnd/NK-2 homeodomain: thermodynamics of reversible unfolding and DNA binding for wild-type and with residue replacements H52R and H52R/T56W in helix III.

The conformational stabilities of the vnd (ventral nervous system defective)/NK-2 homeodomain [HD(wt); residues 1-80 that encompass the 60-residue homeodomain] and those harboring mutations in helix III of the DNA recognition site [HD(H52R) and HD(H52R/T56W)] have been investigated by differential scanning calorimetry (DSC) and ellipticity changes at 222 nm. Thermal unfolding reactions at pH 7.4 are reversible and repeatable in the presence of 50-500 mM NaCl with DeltaC(p) = 0.52 +/- 0.04 kcal K(-1) mol(-1). A substantial stabilization of HD(wt) is produced by 50 mM phosphate or by the addition of 100-500 mM NaCl to 50 mM Hepes, pH 7.4, buffer (from T(m) = 35.5 degrees C to T(m) 43-51 degrees C; DeltaH(vH) congruent with 47 +/- 5 kcal mol(-1)). The order of stability is HD(H52R/T56W) > HD(H52R) > HD(wt), irrespective of the anions present. Progress curves for ellipticity changes at 222 nm as a function of increasing temperature are fitted well by a two-state unfolding model, and the cooperativity of secondary structure changes is greater for mutant homeodomains than for HD(wt) and also is increased by adding 100 mM NaCl to Hepes buffer. A 33% quench of the intrinsic tryptophanyl residue fluorescence of HD(wt) by phosphate binding (K(D)' = 2.6 +/- 0.3 mM phosphate) is reversed approximately 60% by DNA binding. Thermodynamic parameters for vnd/NK-2 homeodomain proteins binding sequence-specific 18 bp DNA have been determined by isothermal titration calorimetry (10-30 degrees C). Values of DeltaC(p) are +0.25, -0.17, and -0.10 +/- 0.04 kcal K(-1) mol(-1) for HD(wt), HD(H52R), and HD(H52R/T56W) binding duplex DNA, respectively. Interactions of homeodomains with DNA are enthalpically controlled at 298 K and pH 7.4 with corresponding DeltaH values of -6.6 +/- 0.5, -10.8 +/- 0.1, and -9.0 +/- 0.6 kcal mol(-1) and DeltaG' values of -11.0 +/- 0.1, -11.0 +/- 0.1, and -11.3 +/- 0.3 kcal mol(-1) with a binding stoichiometry of 1.0 +/- 0.1. Thermodynamic parameters for DNA binding are not predicted from homeodomain structural changes that occur upon complexing to DNA and must reflect also solvent and possibly DNA rearrangements.

Amino Acid Substitution↗
PubMed2001

Equine herpesvirus protein E10 induces membrane recruitment and phosphorylation of its cellular homologue, bcl-10.

v-E10, a caspase recruitment domain (CARD)-containing gene product of equine herpesvirus 2, is the viral homologue of the bcl-10 protein whose gene was found to be translocated in mucosa-associated lymphoid tissue (MALT) lymphomas. v-E10 efficiently activates the c-jun NH(2)-terminal kinase (JNK), p38 stress kinase, and the nuclear factor (NF)-kappaB transcriptional pathway and interacts with its cellular homologue, bcl-10, via a CARD-mediated interaction. Here we demonstrate that v-E10 contains a COOH-terminal geranylgeranylation consensus site which is responsible for its plasma membrane localization. Expression of v-E10 induces hyperphosphorylation and redistribution of bcl-10 from the cytoplasm to the plasma membrane, a process which is dependent on the intactness of the v-E10 CARD motif. Both membrane localization and a functional CARD motif are important for v-E10-mediated NF-kappaB induction, but not for JNK activation, which instead requires a functional v-E10 binding site for tumor necrosis factor receptor-associated factor (TRAF)6. Moreover, v-E10-induced NF-kappaB activation is inhibited by a dominant negative version of the bcl-10 binding protein TRAF1, suggesting that v-E10-induced membrane recruitment of cellular bcl-10 induces constitutive TRAF-mediated NF-kappaB activation.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Dendritic cell longevity and T cell persistence is controlled by CD154-CD40 interactions.

Inflammatory mediators facilitate the maturation of dendritic cells (DC), enabling them to induce the activation, proliferation and differentiation of cognate T cells. The role of CD40 on DC and CD154 on T cells has been studied by the co-adoptive transfer of antigen-pulsed DC and TCR-transgenic (Tg) T cells in vivo. It is shown that in the absence of CD40-CD154 interactions, initial Tg T cell expansion occurs in vivo, but over time, T cell expansion cannot be sustained. The basis for the demise of the T cell population is likely due to the disappearance of the antigen-pulsed DC in the draining lymph nodes when CD154-CD40 interactions are interrupted. These findings show that both T cell and DC persistence in vivo is dependent on CD40-CD154 interactions. In addition to the physical persistence of the DC, CD40 triggering of DC also greatly increases the period for which they can productively present antigen to Tg T cells. Hence DC persistence and antigen-presenting cell capacity are both dependent on CD40 signaling. While TNF-alpha can mature DC as measured by a variety of criteria, the unique capacity of CD40 signaling to sustain T cell responses and induce DC maturation is underscored by the inability of TNF-alpha to rescue the immune deficiency of CD40(-/-) DC. Hence, the profound impact of CD154 deficiency on cell-mediated immunity may be due to its ability to limit the duration of antigen presentation in vivo and cause the premature demise of antigen-specific T cells.

Adoptive Transfer↗
PubMed2001

Immunophenotypic analysis of the TCR-Vbeta repertoire in 98 persistent expansions of CD3(+)/TCR-alphabeta(+) large granular lymphocytes: utility in assessing clonality and insights into the pathogenesis of the disease.

At present, a major challenge in the initial diagnosis of leukemia of large granular lymphocytes (LGLs) is to establish the clonal nature of the expanded population. In the present study we have analyzed by flow cytometry immunophenotyping the TCR-Vbeta repertoire of 98 consecutive cases of persistent expansions of CD4(+) or CD8(+bright) CD3(+)/TCR-alphabeta(+) LGLs and compared the results with those obtained in molecular studies of TCR-beta gene rearrangements. Fifty-eight cases were considered to be monoclonal in molecular studies whereas in the remaining 40 cases there was no evidence for monoclonality (11 cases were considered oligoclonal and 29 polyclonal). The TCR-Vbeta repertoire was biased to the preferential use of one or more TCR-Vbeta families in 96% of cases, a total of 124 TCR-Vbeta expansions being diagnosed: one TCR-Vbeta expansion in 71 cases and two or more TCR-Vbeta expansions in 23 cases. The highest TCR-Vbeta expansion observed in each case was higher among monoclonal (74 +/- 19%) as compared to nonmonoclonal cases (24 +/- 14%) (P = 0.001), as did the fraction of LGLs that exhibited a TCR-Vbeta-restricted pattern (86 +/- 16% and 42 +/- 23%, respectively; P = 0.0001); by contrast, the proportion of cases displaying more than one TCR-Vbeta expansion was higher in the latter group: 7% versus 48%, respectively (P = 0.001). Results obtained in oligoclonal cases were intermediate between those obtained in polyclonal and monoclonal cases and similar results were observed for CD4(+) as for CD8(+bright) T-cell expansions. TCR-Vbeta families expressed in CD8(+bright) T-cell-LGL proliferations showed a pattern of distribution that mimics the frequency at which the individual TCR-Vbeta families are represented in normal peripheral blood T cells. Assuming that a given proliferation of LGLs is monoclonal whenever there is an expansion of a given TCR-Vbeta family of at least 40% of the total CD4(+) or CD8(+bright) T-cell compartment, we were able to predict clonality with a sensitivity of 93% and a specificity of 80%. By increasing the cut-off value to 60%, sensitivity and specificity were of 81% and 100%. In summary, our results suggest that flow cytometry immunophenotypic analysis of the TCR-Vbeta repertoire is a powerful screening tool for the assessment of T-cell clonality in persistent expansions of TCR-alphabeta(+) LGLs.

Adolescent↗
PubMed2001

Solving probabilistic and statistical problems: a matter of information structure and question form.

Is the human mind inherently unable to reason probabilistically, or is it able to do so only when problems tap into a module for reasoning about natural frequencies? We suggest an alternative possibility: naive individuals are able to reason probabilistically when they can rely on a representation of subsets of chances or frequencies. We predicted that naive individuals solve conditional probability problems if they can infer conditional probabilities from the subset relations in their representation of the problems, and if the question put to them makes it easy to consider the appropriate subsets. The results of seven studies corroborated these predictions: when the form of the question and the structure of the problem were framed so as to activate intuitive principles based on subset relations, naive individuals solved problems, whether they were stated in terms of probabilities or frequencies. Otherwise, they failed with both sorts of information. The results contravene the frequentist hypothesis and the evolutionary account of probabilistic reasoning.

Adult↗
PubMed2001

Nutritional value of the marine invertebrates Anemonia viridis and Haliothis tuberculata and effects on serum cholesterol concentration in ratsopen star

The purpose of this study was to determine the nutritional value of diets with protein from two marine species (Haliotis tuberculata and Anemonia viridis) as compared to a high-quality protein reference based on casein or casein supplemented with olive oil. We also investigated the effects of these diets on serum lipid levels. Male rats were fed these diets for 23 days. Protein quality indicators (true digestibility, net protein utilization, biological value) were similar to those obtained for casein-based feeds except for lower true digestibility and net protein utilization values for the Anemonia viridis feed. HDL-cholesterol level was significantly higher (p < 0.05) in the groups fed marine species or casein supplemented with olive oil than in the casein group. Total-cholesterol level was higher in the group fed Haliotis tuberculata fed than in the other groups. These results suggest that these marine species are a good protein source, and that they may have positive effects on serum cholesterol level.

Journal Article↗
PubMed2001

Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo.

Skeletal muscles adapt to changes in their workload by regulating fibre size by unknown mechanisms. The roles of two signalling pathways implicated in muscle hypertrophy on the basis of findings in vitro, Akt/mTOR (mammalian target of rapamycin) and calcineurin/NFAT (nuclear factor of activated T cells), were investigated in several models of skeletal muscle hypertrophy and atrophy in vivo. The Akt/mTOR pathway was upregulated during hypertrophy and downregulated during muscle atrophy. Furthermore, rapamycin, a selective blocker of mTOR, blocked hypertrophy in all models tested, without causing atrophy in control muscles. In contrast, the calcineurin pathway was not activated during hypertrophy in vivo, and inhibitors of calcineurin, cyclosporin A and FK506 did not blunt hypertrophy. Finally, genetic activation of the Akt/mTOR pathway was sufficient to cause hypertrophy and prevent atrophy in vivo, whereas genetic blockade of this pathway blocked hypertrophy in vivo. We conclude that the activation of the Akt/mTOR pathway and its downstream targets, p70S6K and PHAS-1/4E-BP1, is requisitely involved in regulating skeletal muscle fibre size, and that activation of the Akt/mTOR pathway can oppose muscle atrophy induced by disuse.

Animals↗