Search PubMed⌕ Search

Biomedical subjects

R Gonzalez

Publications and source records attributed to R Gonzalez.

At least 73 records · Page 4Linked to original sources
PubMed1999

The GATA factor AreA is essential for chromatin remodelling in a eukaryotic bidirectional promoter.

The linked niiA and niaD genes of Aspergillus nidulans are transcribed divergently. The expression of these genes is subject to a dual control system. They are induced by nitrate and repressed by ammonium. AreA mediates derepression in the absence of ammonium and NirA supposedly mediates nitrate induction. Out of 10 GATA sites, a central cluster (sites 5-8) is responsible for approximately 80% of the transcriptional activity of the promoter on both genes. We show occupancy in vivo of site 5 by the AreA protein, even under conditions of repression. Sites 5-8 are situated in a pre-set nucleosome-free region. Under conditions of expression, a drastic nucleosomal rearrangement takes place and the positioning of at least five nucleosomes flanking the central region is lost. Remodelling is strictly dependent on the presence of an active areA gene product, and independent from the NirA-specific and essential transcription factor. Thus, nucleosome remodelling is independent from the transcriptional activation of the niiA-niaD promoter. The results presented cast doubts on the role of NirA as the unique transducer of the nitrate induction signal. We demonstrate, for the first time in vivo, that a GATA factor is involved directly in chromatin remodelling.

Aspergillus nidulans↗
PubMed1999

Bilateral medial pectoral neuropathy in a weight lifter.

Weight lifting has occasionally been associated with focal neuropathies of unknown cause. We describe a case of progressive bilateral medial pectoral neuropathy in a body builder. Whereas the medial pectoral nerve passes through pectoralis minor to reach the pectoralis major, the lateral pectoral nerve has no such intramuscular course. We postulate that weight lifting and concomitant pectoralis minor hypertrophy in our patient produced intramuscular entrapment of the medial pectoral nerves.

Adult↗
PubMed1999

On the shape of the probability weighting function.

Empirical studies have shown that decision makers do not usually treat probabilities linearly. Instead, people tend to overweight small probabilities and underweight large probabilities. One way to model such distortions in decision making under risk is through a probability weighting function. We present a nonparametric estimation procedure for assessing the probability weighting function and value function at the level of the individual subject. The evidence in the domain of gains supports a two-parameter weighting function, where each parameter is given a psychological interpretation: one parameter measures how the decision maker discriminates probabilities, and the other parameter measures how attractive the decision maker views gambling. These findings are consistent with a growing body of empirical and theoretical work attempting to establish a psychological rationale for the probability weighting function.

Humans↗
PubMed1999

Maximal and explosive force production capacity and balance performance in men of different ages.

A group of 32 healthy men (M) divided into three different age groups, i.e. M20 years [mean 21 (SD 1); n = 12], M40 [mean 40 (SD 2); n = 10] and M70 [mean 71 (SD 5); n = 10] volunteered as subjects for examination of maximal and explosive force production of leg extensor muscles in both isometric and dynamic actions (squat jump, SJ and counter movement jump, CMJ, and standing long-jump, SLJ). The balance test was performed on a force platform in both isometric and dynamic actions. Maximal bilateral isometric force value in M70 was lower (P < 0.001) than in M40 and as much as 46% lower (P < 0.001) than that recorded in M20 (P < 0.001). The maximal rate of force development (RFD) on the force-time curve was in M70 lower (P < 0.001) than in M40 and as much as 64% lower than in M20. The heights in SJ and CMJ and the distance in SLJ in M70 were lower (P < 0.001) than in M40 and M20 (P < 0.001). In response to modifications of the visual surroundings the older subjects were 24%-47% (P < 0.05 and P < 0.001) slower in their response time in reaching the lit centre (TT) and remained 20%-34% (P < 0.001) less time inside the centre (TC) from the overall time of lighting than M40 and M20, respectively. In both older groups the individual values of isometric RFD correlated significantly (P < 0.05) with the individual balance values of TT and TC. The present results would suggest that the capacity for explosive force production declines drastically with increasing age, even more than maximal muscle strength. Aging may also lead to impaired balance with a decrease in event detection and speed of postural adjustments. The decreased ability to develop force rapidly in older people seems to be associated with a lower capacity for neuromuscular response in controlling postural sway.

Adult↗
PubMed1999

Quantitative nuclear cystography does not predict outcome in patients with primary vesicoureteral reflux.

PURPOSE: Quantitative nuclear cystography has been advocated as a tool for determining the prognosis in children with primary vesicoureteral reflux. We reviewed our data on this technique to assess its usefulness for predicting the outcome in this population. MATERIALS AND METHODS: We retrospectively reviewed the records of all patients with primary reflux in whom findings were positive on at least 2 nuclear cystograms at our institution between 1992 and 1997. Patients followed at least 3 years were stratified according to outcome. Unfavorable prognostic criteria included bladder volume at reflux onset 60% or less of total bladder capacity and calculated volume of reflux 2% or greater of bladder capacity. RESULTS: Of the 107 patients in our study 63 were followed for 3 years or longer, and reflux resolved in 17, was repaired in 24 and persisted in 22. Mean patient age at latest followup, duration of followup and number of cystograms did not significantly differ among groups. Intermittent reflux in 33% of the patients followed 3 years or longer was not associated with outcome or detrusor instability. Bladder and reflux volume varied and was nonpredictive in individuals. CONCLUSIONS: Quantitative nuclear cystography did not predict the outcome in patients followed for primary vesicoureteral reflux at a single institution for 3 years or longer. Intermittent reflux was common. These data suggest that nuclear cystography cannot be used to assess reliably the prognosis in individuals. Strong consideration should be given to using negative findings on 2 cystograms to confirm reflux resolution in patients at high risk.

Adolescent↗
PubMed1999

Loss of heterozygosity in BRCA1 and BRCA2 markers and high-grade malignancy in breast cancer.

Loss of heterozygosity (LOH) in loci of the 17q21 and 13q12-13 regions can collaborate in the inactivation of BRCA1, BRCA2, and possibly other genes implicated in the pathogenesis of breast carcinomas. We investigate allelic losses in microsatellites of the BRCA1 and BRCA2 regions, and their correlations with seven pathologic parameters in 140 breast carcinomas. Those cases showing LOH in the region of the RB gene, 13q14, were excluded from the study. The LOH analysis was performed by amplifying DNA by PCR, using four markers of the 17q21 region (D17S856, D17S855, D17S1323, and D17S1327) and four markers of the 13q12-13 region (D13S290, D13S260, D13S310, and D13S267). LOH in the BRCA1 region was found in 47% of tumors, correlating significantly with estrogen receptor content (p = 0.025), progesterone receptors (p = 0.004), higher grade (p = 0.0008), peritumoral vessel invasion (p = 0.001), and lymph node metastases (p = 0.002). When we excluded the cases with LOH in the BRCA2 region and those not informative for it, the significance disappeared. In the BRCA2 region, a rate of LOH of 51% was found; it correlated significantly with estrogen receptor content (p = 0.002), progesterone receptors (p = 0.03), peritumoral vessel invasion (p = 0.005), higher grade (p = 0.002), and lymph node metastases (p = 0.001). When cases with BRCA1 losses and those not informative were excluded, again the significance disappeared. Concomitant losses in the BRCA1 and BRCA2 regions were found in 32% of cases, correlating significantly with lymph node metastases (p = 0.0002), estrogen receptor content (p = 0.003), progesterone receptors (p = 0.001), histologic grade (p = 0.01), and peritumoral vessel invasion (p = 0.0004). These results suggest that concomitant losses in both regions could have a functional effect, influencing the presence of a poor tumor pathophenotype in breast carcinomas.

Adenocarcinoma↗
PubMed1999

Allelic loss of the PTEN region (10q23) in breast carcinomas of poor pathophenotype.

Loss of heterozygosity (LOH) in loci of the 10q23 region that harbor the PTEN gene and mutations in the sequence of this gene have been found in several primary human tumors including breast carcinomas, suggesting that this gene could be implicated in their pathogenesis. We investigated allelic losses in microsatellites of the 10q23 region, and their correlations with nine pathologic parameters in 105 breast carcinomas. The LOH analysis was performed by amplifying DNA by PCR, using five markers of the 10q23 region (D10S1687, D10S541, D10S2491, D10S583 and D10S571). LOH in at least one marker of the PTEN region was found in 29.5% of tumors. The statistical comparison between carcinomas with and without LOH in terms of the pathologic parameters showed significant differences in age (p = 0.03), lymph node metastases (p = 0.02), and higher histological grade (p = 0.02); a trend toward significance was found for progesterone receptors (p = 0.05). LOH in an individual marker and statistically significant relationships to tumor characteristics were observed at locus D10S541 for lymph node metastases (p = 0.04), at D10S2491 (intragenic to the PTEN gene) for lymph node metastases (p = 0.02), and at D10S583 for progesterone receptors (p = 0.01) and for high grade (p = 0.03). These results suggest the PTEN gene, or other genes of the 10q23 region, could be functionally related to breast cancer, probably influencing the development of histological features associated with poor prognosis.

Breast Neoplasms↗
PubMed1999

Aberrant DNA methylation of the p16INK4a gene in plasma DNA of breast cancer patients.

Hypermethylation of exon 1 of p16INK4a was examined in tumour and plasma DNA of a series of breast cancer patients. De novo methylation was observed in the tumours of eight patients (23%), and in plasma DNA in five (14%) of these eight patients. Our data show that de novo methylation of exon 1 of p16INK4a can be demonstrated in plasma DNA of breast cancer patients, a fact that provides additional evidence of the tumour-related origin of free plasma DNA in cancer patients.

Amino Acid Sequence↗
PubMed1999

Detection of loss of heterozygosity at RAD51, RAD52, RAD54 and BRCA1 and BRCA2 loci in breast cancer: pathological correlations.

Loss of heterozygosity (LOH) in loci of the 15q15.1, 12p13, 1p32, 17q21 and 13q12-13 regions may collaborate in the inactivation of RAD51, RAD52, RAD54, BRCA1, BRCA2 and possibly other genes implicated in the repair of double-stranded DNA and in DNA recombination. We investigate allelic losses in microsatellites of the RAD51, RAD52, RAD54, BRCA1 and BRCA2 regions, and their correlations with nine pathologic parameters in 127 breast carcinomas. The LOH analysis was performed by amplifying DNA by PCR, using 15 markers of the 15q15.1, 12p13.3, 1p32, 17q21 and 13q12-13 regions. LOH was found in the RAD51 region in 32% of tumours, in the RAD52 region in 16%, in RAD54 in 20% and in the BRCA1 and BRCA2 regions in 49% and 44% respectively. Significant correlations between one or more regions with concomitant LOH and pathologic parameters were observed with respect to age (P = 0.008), oestrogen receptor content (P = 0.03), progesterone receptors (P = 0.003), higher grade (P = 0.001), more advanced stage (P = 0.004) and peritumoural vessel involvement (P < 0.0001). The number of cases in which LOH was observed simultaneously in two or more regions was always higher than expected on the basis of their statistical probability, and curiously, the three patients with LOH at five regions concomitantly were under the age of 30 years. These results suggest that LOH at these regions could be related to breast cancer, and probably to a poor tumour prognosis.

Age Factors↗
PubMed1999

Increased gene transfer in acute myeloid leukemic cells by an adenovirus vector containing a modified fiber protein.

Applications of gene transfer in acute myeloid leukemia (AML) blast cells have still not been developed, mostly due to the lack of an efficient vector. Adenoviruses have many advantages as vectors, but remain poorly efficient in cells lacking fiber receptors. A promising strategy is the retargeting of adenoviruses to other cellular receptors. We report the dramatic enhancement of gene transfer efficiency in AML blasts using AdZ.F(pK7), a modified adenovirus containing a heparin/heparan sulfate binding domain incorporated into the fiber protein of the adenovirus. We transduced 25 AML blast samples with efficiency reaching 100% of the cells in most samples. Optimal results were obtained at 8400 physical particles per cell, corresponding to a multiplicity of infection of 100 plaque forming units per cell. Control AdZ.F adenovirus efficiently transduced leukemic cell lines but gave poor results in AML samples. Both addition of soluble heparin and cell treatment with heparinase inhibited AdZ.F(pK7) gene transfer, showing that heparan sulfates are the major receptors mediating AdZ.F(pK7) transduction of AML blasts. Although adenoviruses can infect nondividing cells, we observed that a combination of growth factors (GM-CSF, IL-3, stem cell factor) was required for efficient transduction in order to maintain AML blast cell viability. This study demonstrates that retargeting the adenovirus fiber protein to heparan sulfates can overcome the low efficiency of adenovirus in AML blast cells and may provide a useful tool for gene therapy approaches in AML.

Acute Disease↗
PubMed1999

Efficacy of lipectomy and liposuction in the treatment of multiple symmetric lipomatosis.

BACKGROUND: Multiple symmetric lipomatosis (MSL) is a rare disease characterized by enlarging, symmetric, nonencapsulated, fat deposits mainly on the neck and upper trunk. Liposuction and lipectomy, although palliative, are the treatments of choice, especially indicated when vital structures are compromised. OBJECTIVE: Our purpose was to evaluate the efficacy and safety of liposuction and lipectomy in the treatment of MSL. METHODS: We have examined two patients diagnosed with MSL who presented with symptoms derived from the compression of vascular, nervous, and/or respiratory tract structures. One was treated with lipectomy and the other with liposuction. RESULTS: A rapid resolution of the clinical symptoms was achieved with both therapies. The patient who was treated with lipectomy suffered from a compression of the left brachial plexus by scar tissue as an adverse effect, requiring a second surgical procedure. Liposuction only provoked a mild autoinvolutive hematoma in the other case. No clinical recurrences were observed at 3 and 2 years of follow-up respectively. CONCLUSIONS: We consider both lipectomy and liposuction as safe and effective techniques for the treatment of MSL patients. Although liposuction is usually associated with less adverse effects than lipectomy, location of the lipomas must be carefully considered before choosing one technique over another.

Adult↗
PubMed1999

Treatment of patients with metastatic melanoma with bryostatin-1--a phase II study.

Bryostatin-1 is a protein kinase C regulator which has shown antitumour activity against B16 melanoma in animal models. Safety trials revealed this agent to be minimally toxic, thus a phase II trial of bryostatin-1 was conducted to determine its efficacy In patients with melanoma. Eighteen patients with metastatic melanoma, seven of whom had been previously treated, were enrolled in the study. Patients received bryostatin-1 25 microg/m2 intravenously weekly over 1 h for 3 out of 4 weeks. No objective responses were observed. One patient who had not previously received chemotherapy had stable disease for 4 months, and two patients (one previously treated) had a marked decrease in the skin component of their disease. The major toxicity was myalgia (one patient with grade III, two patients with grade II and five patients with grade I), with no grade IV toxicities reported. To Indirectly evaluate the stimulation of protein kinase C, a sensitive assay that measures the upregulation of the activated form of CD62 (glycoprotein IIb/IIIa) on platelets was performed. There was a statistically significant upregulation of this antigen 1 h after bryostatin-1 therapy. A bioassay based on the ability of bryostatin-1 to bind protein kinase C was used to measure bryostatin-1 levels in serum. This assay showed that bryostatin-1 has a volume of distribution of 2.1 l/m2, an elimination clearance of 32.9 ml/min per m2 and a half-life of 43.9 min. In conclusion, this phase II trial demonstrates that, although it is relatively non-toxic, bryostatin-1 therapy had minimal activity in metastatic melanoma.

Adult↗
PubMed1999

Immunotherapy of advanced malignancy by direct gene transfer of an interleukin-2 DNA/DMRIE/DOPE lipid complex: phase I/II experience.

PURPOSE: We have completed a phase I study, followed by three phase I/II studies, in patients with metastatic melanoma, renal cell carcinoma (RCC), and sarcoma in order to evaluate the safety, toxicity, and antitumor activity of Leuvectin (Vical Inc, San Diego, CA), a gene transfer product containing a plasmid encoding human interleukin (IL)-2 formulated with the cationic lipid 1, 2-dimyristyloxypropyl-3-dimethyl-hydroxyethyl ammonium bromide/dioleyl-phosphatidyl-ethanolamine (DMRIE/DOPE) and administered intratumorally. PATIENTS AND METHODS: Twenty-four patients were treated in the phase I study. Leuvectin doses were 10 microg, 30 microg, or 300 microg weekly for 6 weeks. In three subsequent phase I/II studies, a total of 52 patients (18 with melanoma, 17 with RCC, and 17 with sarcoma) were treated with further escalating doses of Leuvectin: 300 microg twice a week for 3 weeks, 750 microg weekly for 6 weeks, and 1,500 microg weekly for 6 weeks. RESULTS: There were no drug-related grade 4 toxicities and only one grade 3 toxicity, but the majority of patients experienced mild constitutional symptoms after treatment. In the phase I/II studies, 45 patients were assessable for response (14 with RCC, 16 with melanoma, and 15 with sarcoma). Two patients with RCC and one with melanoma have achieved partial responses lasting from 16 to 19 months and continuing. In addition, two RCC, three melanoma, and six sarcoma patients had stable disease lasting from 3 to 18 months and continuing. The plasmid was detected by polymerase chain reaction assay in the posttreatment samples of 29 of 46 evaluated patients. Immunohistochemistry studies on serial biopsy specimens showed increased IL-2 expression and CD8(+) infiltration after treatment in the tumor samples of several patients (12 and 16, respectively). CONCLUSION: Direct intratumoral injection of Leuvectin is a safe and possibly effective immunotherapeutic approach in the treatment of certain tumor types.

Adult↗
PubMed1999

TP53 gene mutations in plasma DNA of cancer patients.

Using different molecular techniques, DNA has been shown to be present in plasma of patients with several types of tumors. Mutations of TP53 are the most common genetic changes in human cancers. We investigated the presence of TP53 gene mutations in plasma DNA of breast and small cell lung cancer patients. Tumor and plasma DNA of 25 patients were studied by PCR-SSCP and direct sequencing, through exons 5, 6, 7, and 8, of TP53. Six cases of mutations in tumor DNA were observed that, in 3 cases (50%), were also identified in plasma of the same patients. Mutations of the TP53 gene are seen in plasma DNA of cancer patients, and may prove to be a useful new tool in the management of these patients.

Breast Neoplasms↗