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Biomedical subjects

A Ramírez

Publications and source records attributed to A Ramírez.

At least 19 recordsLinked to original sources
PubMed2006

Structural and functional characterization of a recombinant sticholysin I (rSt I) from the sea anemone Stichodactyla helianthus.

Sticholysins I and II (Sts I and II) are two potent cytolysins from the sea anemone Stichodactyla helianthus. These isoforms present 13 substitutions, with three non-conservative located at the N-terminus. St II is considerably more hemolytic than St I in human red blood cells, a result explained by the smaller number of negatively charged groups present at St II's N-terminus. In the present work, we have obtained a recombinant St I (rSt I), differing from the wild type in a single amino acid residue (E16Q). This pseudo-wild type is structurally similar to St I and shows a similar capacity to interact with and form pores in model membranes. This was assessed by the intrinsic fluorescence increase in the presence of liposomes, their adsorption to bilayers (measured by SPR), their concentration at the air-water interface, their interaction with lipid monolayers and their capacity to promote the release of carboxyfluorescein entrapped in liposomes. In spite of these similarities, rSt I presents a larger hemolytic activity in human red blood cells than St I, being intermediate in activity between Sts I and II. The results obtained in the present work emphasize that even the change of one single E by Q at the N-terminal segment may modify the toxin HA and show that this functional property is the most sensitive to subtle changes in the protein primary structure.

Amino Acid Sequence↗
PubMed2005

The role of somatostatin receptor scintigraphy in patients with pituitary adenoma or post-surgical recurrent tumours.

To assess the role of scintigraphy with 111In-DTPA-D-Phe-octreotide (111In-octreotide) in the diagnosis of pituitary adenomas and in the evaluation of post-surgical recurrent or residual tumours, we performed scintigraphy with 111In-DTPA-D-Phe-octreotide (SRS) in 35 patients: 14 patients with confirmed pituitary tumours and 15 with confirmed recurrent tumours. Clinical, biochemical and histological analyses, conventional images (CT/MRI), and follow-up assessments during a period of 1 year to 4 years were recorded in all patients. In the present study, scintigraphy with 111In-octreotide showed positive uptake in 10 out of 14 patients with confirmed pituitary tumour and in 13 out of 15 patients with confirmed recurrent tumour, with an overall sensitivity of 79%. SRS showed better results in growth hormone (GH)- and prolactin (PRL)-secreting tumours (7/8 patients correctly identified) than in other adenomas (3/9). SRS detected recurrence of adenocorticotrophic hormone (ACTH)-secreting tumours (4/5 patients correctly identified) and non-secreting tumours (5/7 patients correctly identified). 111In-octreotide scintigraphy, in combination with other imaging modalities, is useful in the diagnosis and follow-up of pituitary tumours. It allows scar tissue to be differentiated from tumour recurrence after surgical treatment and ensures better selection of patients who will benefit from medical treatment with somatostatin analogues.

Adenoma↗
PubMed2004

Mathematical modeling of electro-rotation spectra of small particles in liquid solutions: application to human erythrocyte aggregates.

Electro-rotation can be used to determine the dielectric properties of cells, as well as to observe dynamic changes in both dielectric and morphological properties. Suspended biological cells and particles respond to alternating-field polarization by moving, deforming or rotating. While in linearly polarized alternating fields the particles are oriented along their axis of highest polarizability, in circularly polarized fields the axis of lowest polarizability aligns perpendicular to the plane of field rotation. Ellipsoidal models for cells are frequently applied, which include, beside sphere-shaped cells, also the limiting cases of rods and disks. Human erythrocyte cells, due to their particular shape, hardly resemble an ellipsoid. The additional effect of rouleaux formation with different numbers of aggregations suggests a model of circular cylinders of variable length. In the present study, the induced dipole moment of short cylinders was calculated and applied to rouleaux of human erythrocytes, which move freely in a suspending conductive medium under the effect of a rotating external field. Electro-rotation torque spectra are calculated for such aggregations of different length. Both the maximum rotation speeds and the peak frequencies of the torque are found to depend clearly on the size of the rouleaux. While the rotation speed grows with rouleaux length, the field frequency nu(p) is lowest for the largest cell aggregations where the torque shows a maximum.

Cell Polarity↗
PubMed2004

Variation in indoor thoron levels in Mexico City dwellings.

This paper presents the results obtained for thoron concentration in 50 single-family dwellings in normal occupancy conditions (open house conditions), measured by a passive electret system (type E-PERM, SSTB configuration) in a 2001-2002 monitoring survey in the Metropolitan Zone of Mexico City. The results show the general log-normal distribution of integrated indoor thoron concentration with annual arithmetic and geometric means of 82 and 55 Bq m(-3), respectively, with ranges from 8 to 234 Bq m(-3) higher than world average of 3 Bq m(-3). The seasonal variation shows the minimum mean values in the summer season that were 35% lower than in autumn.

Air Pollutants, Radioactive↗
PubMed2004

Epidemiological relatedness of methicillin-resistant Staphylococcus aureus from a tertiary hospital and a geriatric institution in Spain.

From January 2000 to June 2002, 24 Staphylococcus aureus isolates were recovered from decubitus ulcers of patients in a geriatric institution, of which 17 (70.8%) were methicillin-resistant S. aureus (MRSA). Antibiotic resistance and DNA macrorestriction (pulsed-field gel electrophoresis; PFGE) patterns of the MRSA isolates were compared with a collection of 161 MRSA isolates from patients admitted to the institution's reference hospital. PFGE revealed the presence of five clonal types (found also in hospitalised patients) among the 17 MRSA isolates. The findings suggest nosocomial acquisition of the MRSA strains by five patients, with subsequent dissemination of the strains within the institution. The high rate of MRSA highlights the need for epidemiological analysis to control the dissemination of MRSA in long-term care facilities.

Aged↗
PubMed2004

A new neovalve type in short bowel syndrome surgery.

The objective of this study was to compare the clinical and analytical repercussion of a new type of intestinal valve -which can be used in both massive resections and right hemicolectomies requiring the elimination of the ileocecal valve- on two historical series of patients: one group with ileocolic resections and end-to-end anastomoses (EE), and one group with Ricotta valves. We compared 23 patients with ileocolic resection and end-to-end anastomosis, 15 with Ricotta's valve, and 20 patients with a new valve made with a small intestinal invagination. There were no statistically significant differences in baseline characteristics among patients. Patients with the new valve showed less relevant weight loss and fewer stools at 3 months and one year when compared to patients with Ricotta's valve, and particularly those with ileocolic resection. Moreover, with the new valve technique there was neither colonization of the ileal mucosa nor bacterial overgrowth. In conclusion, in massive intestinal resections and right hemicolectomies, including the ileocecal valve, the new valve technique would be of choice.

Adult↗
PubMed2003

An assessment of wall motion, perfusion and glucose metabolism in recent myocardial infarction: a comparison in patients with and without revascularization.

The aim of this study was to compare the extent and severity of wall motion abnormalities, perfusion and glucose metabolism, in recent myocardial infarction in patients with and without revascularization. Forty-nine patients were studied (82% men; mean age 58 years) by using echocardiography, 201Tl single photon emission computed tomography (SPECT) rest and redistribution, and 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) SPECT at a mean of 9.2 days (range, 1-24 days) after myocardial infarction. Twenty-seven of the 49 patients underwent revascularization while the other 22 received medical therapy before echocardiography and studies using radionuclides. A contrast angiogram was obtained for each patient. A follow-up echocardiogram at 3 months was obtained for 44 patients. Images were read blindly, using a 17 segment model, with semi-quantitative analysis. In the whole group, the extent of hypokinesia was 15%+/-14 (mean+/-SD); the extent of mild defects was determined as 5%+/-6 by using 201Tl at rest, 6%+/-9 by using 201Tl redistribution, and 4%+/-6 by using 18F-FDG (P<0.0005, echocardiogram/radionuclides). Echocardiography showed that the extent of akinesia-dyskinesia was 16%+/-18 in revascularized patients and 28%+/-18 in non-revascularized patients (P=0.017). With regard to moderate and severe defects, 201Tl rest showed 19%+/-16 and 28%+/-17, respectively (P=0.047); 201Tl redistribution 17%+/-15 and 26%+/-15, respectively (P=0.043); and 18F-FDG 17%+/-13 and 24%+/-15, respectively (NS). In echocardiography, the extent of hypokinetic segments decreased from 16%+/-15 at baseline to 10%+/-11 at 3 months (P=0.045), in revascularized patients. It is concluded that, in recent myocardial infarction, hypokinesia extent on echocardiogram is greater than mild perfusion or metabolic defect extent, reflecting stunning and so the use of radionuclide techniques appear more accurate for defining the extent of myocardial infarction. Non-revascularized patients showed a significantly greater extent of akinesia-dyskinesia and moderate-severe perfusion defects than did revascularized patients, which can be considered a result of therapy. It is suggested that 201Tl rest perfusion be used for the assessment of myocardial infarction soon after revascularization.

Adult↗
PubMed2002

The curcuma antioxidants: pharmacological effects and prospects for future clinical use. A review.

In agreement with the predictions of the oxygen-stress theory of aging and age-related degenerative diseases, diet supplementation with a number of phenolic or thiolic antioxidants has been able to increase the life span of laboratory animals, protect against senescent immune decline and preserve the respiratory function of aged mitochondria. In addition to the above, more recent data reviewed here suggest that the polyphenolic compound curcumin and related non-toxic antioxidants from the rhizome of the spice plant Curcuma longa have a favorable effect on experimental mouse tumorigenesis as well as on inflammatory processes such as psoriasis and ethanol-caused hepatic injury. Our own research has focused on the effects of diet supplementation with an antioxidant-rich hydroalcoholic extract of the curcuma rhizome on key risk factors of atherogenesis and related cardiovascular disease. Our reviewed data show that, in human healthy subjects, the daily intake of 200 mg of the above extract results in a decrease in total blood lipid peroxides as well as in HDL and LDL-lipid peroxidation. This anti-atherogenic effect was accompanied by a curcuma antioxidant-induced normalization of the plasma levels of fibrinogen and of the apo B/apo A ratio, that may also decrease the cardiovascular risk. The reviewed literature indicates that curcumin and related plant co-antioxidants are powerful anti-inflammatory agents. Further, since they potentiate the anti-atherogenic effect of alpha-tocopherol, more extensive clinical testing of their probable usefulness in cardiovascular risk reduction seems justified.

Journal Article↗
PubMed2001

Characterization of ADAMTS14, a novel member of the ADAMTS metalloproteinase family.

ADAMTS (a disintegrin-like and metalloproteinase domain with thrombospondin type 1 modules) proteins constitute a family of zinc metalloproteinases which target and process extracellular matrix proteins. We cloned and characterized a novel human ADAMTS gene, ADAMTS14, which is located on human chromosome 10q2. ADAMTS14 exhibits the characteristic multidomain structure of ADAMTS proteins including four thrombospondin modules and shows highest similarity to ADAMTS3 and ADAMTS2. By RT-PCR analysis we demonstrated that ADAMTS14 is expressed in human retina and also at low levels in adult brain, lung and placenta.

ADAM Proteins↗
PubMed2001

Increased epidermal tumors and increased skin wound healing in transgenic mice overexpressing the catalytic subunit of telomerase, mTERT, in basal keratinocytes.

Telomerase transgenics are an important tool to assess the role of telomerase in cancer, as well as to evaluate the potential use of telomerase for gene therapy of age-associated diseases. Here, we have targeted the expression of the catalytic component of mouse telomerase, mTERT, to basal keratinocytes using the bovine keratin 5 promoter. These telomerase-transgenic mice are viable and show histologically normal stratified epithelia with high levels of telomerase activity and normal telomere length. Interestingly, the epidermis of these mice is highly responsive to the mitogenic effects of phorbol esters, and it is more susceptible than that of wild-type littermates to the development skin tumors upon chemical carcinogenesis. The epidermis of telomerase-transgenic mice also shows an increased wound-healing rate compared with wild-type littermates. These results suggest that, contrary to the general assumption, telomerase actively promotes proliferation in cells that have sufficiently long telomeres and unravel potential risks of gene therapy for age-associated diseases based on telomerase upregulation.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2001

Fungal infections in patients with solid tumors treated with high-dose chemotherapy and autologous peripheral blood stem cell transplantation.

The incidence and risk factors for fungal infection were assessed in 291 patients who had solid tumors and were undergoing autologous peripheral blood stem cell transplantation. The first 162 patients received prophylactic itraconazole, and 129 patients received nystatin. Empiric amphotericin B was given at day 7 of febrile neutropenia. Fungal infections developed in 52 patients: 47 (16%) were superficial and 6 (2%) were systemic. Itraconazole prophylaxis and only a few days of febrile neutropenia were independently associated with a decrease in the incidence of superficial infections. Only two patients required empiric amphotericin B. Systemic antifungal prophylaxis does not seem to be justified for patients with solid tumors and autologous peripheral blood stem cell transplantation. Empiric amphotericin B may be safely started at day 7 of febrile neutropenia.

Adolescent↗
PubMed2001

[Invassive infections caused by Group A streptococci: clinical characteristics and microbiological analyses in 31 cases].

BACKGROUND: In the last two decades an increase in the incidence of invassive Streptococcus pyogenes infections has been reported in several countries. The objective of this study was to determine the clinical features of these infections in our hospital. METHODS: Retrospective study (1995-1998) of patients admitted at Son Dureta Hospital, Palma de Mallorca, Spain, who had S. pyogenes recovered from blood, sterile fluids or soft tissues. Patients clinical records were reviewed and bacterial isolates characterized. RESULTS: A total of 31 patients with invassive infections caused by S. pyogenes were identified. The annual incidence rates (number of episodes/1,000 admissions) were: 0.13 (1995), 0.20 (1996), 0.27 (1997), and 0.23 (1998). The mean age of patients was 41 years. Seventy four percent of patients had some underlying disease, and the most relevant conditions included: diabetes mellitus (5), parenteral drug abuse (4), chronic alcoholism (3), chronic liver disease (3) and infection with the human immunodeficiency virus (3). The most common portal of entry was the skin (78%). The initial clinical presenting form was cellulitis (39%). Necrotizing fasciitis, septic shock, and streptococcal toxic shock syndrome (STSS) were observed in 9.6%, 12.9%, and 6.4% of patients, respectively. The mortality rate was 16.1%. The phenotypic characterization of S. pyogenes isolates indicated that most isolates were of mucoid type and identified 11 different M serotypes, M1 being the most common. CONCLUSIONS: A steady increase in the incidence of invassive infections caused by S. pyogenes was observed since 1995 to 1997 in our hospital. Patients with certain underlying conditions are more susceptible to acquire these infections. The worst outcome of these infections corresponded to elderly patients, those with septic shock or STSS. Most strains responsible for these infections were encapsulated and the M1 serotype predominated.

Adolescent↗
PubMed2001

Mutation of CDH23, encoding a new member of the cadherin gene family, causes Usher syndrome type 1D.

Usher syndrome type I (USH1) is an autosomal recessive disorder characterized by congenital sensorineural hearing loss, vestibular dysfunction and visual impairment due to early onset retinitis pigmentosa (RP). So far, six loci (USH1A-USH1F) have been mapped, but only two USH1 genes have been identified: MYO7A for USH1B and the gene encoding harmonin for USH1C. We identified a Cuban pedigree linked to the locus for Usher syndrome type 1D (MIM 601067) within the q2 region of chromosome 10). Affected individuals present with congenital deafness and a highly variable degree of retinal degeneration. Using a positional candidate approach, we identified a new member of the cadherin gene superfamily, CDH23. It encodes a protein of 3,354 amino acids with a single transmembrane domain and 27 cadherin repeats. In the Cuban family, we detected two different mutations: a severe course of the retinal disease was observed in individuals homozygous for what is probably a truncating splice-site mutation (c.4488G-->C), whereas mild RP is present in individuals carrying the homozygous missense mutation R1746Q. A variable expression of the retinal phenotype was seen in patients with a combination of both mutations. In addition, we identified two mutations, Delta M1281 and IVS51+5G-->A, in a German USH1 patient. Our data show that different mutations in CDH23 result in USH1D with a variable retinal phenotype. In an accompanying paper, it is shown that mutations in the mouse ortholog cause disorganization of inner ear stereocilia and deafness in the waltzer mouse.

Alternative Splicing↗
PubMed2001

Mutations in CAV3 cause mechanical hyperirritability of skeletal muscle in rippling muscle disease.

Hereditary rippling muscle disease (RMD) is an autosomal dominant human disorder characterized by mechanically triggered contractions of skeletal muscle. Genome-wide linkage analysis has identified an RMD locus on chromosome 3p25. We found missense mutations in positional candidate CAV3 (encoding caveolin 3; ref. 5) in all five families analyzed. Mutations in CAV3 have also been described in limb-girdle muscular dystrophy type 1C (LGMD1C; refs. 6,7), demonstrating the allelism of dystrophic and non-dystrophic muscle diseases.

Caveolin 3↗
PubMed2001

Sequence and chromosomal context effects on variegated expression of keratin 5/lacZ constructs in stratified epithelia of transgenic mice.

The expression of transgene loci in mammals often occurs in a heterocellular fashion resulting in variegated patterns of expression. We have examined the effect of chromosomal integration site, copy number, and transcriptionally activating sequences on the variegation of a keratin 5-lacZ (K5Z) construct in the stratified epithelia of transgenic mice. lacZ expression in these mice is always mosaic, and the beta-gal activity per cell is usually higher in the lines with a higher proportion of expressing cells. Similar constructs, in which cDNAs were exchanged by lacZ sequences, showed no variegation. Also, when a strongly active, nonvariegating construct was coinjected with K5Z, most transgenic lines showed an almost homogeneous lacZ expression. The comparison of transgene arrays of different copies inserted at the same locus (obtained by using a lox/Cre system) showed that the reduction of copy number does not lead to an increase in the proportion of cells that express the transgene. Finally, in most of the variegating or nonexpressing lines the transgenes were located both at intermediate positions and at peritelomeric regions in the long chromosome arms. These findings suggest that the probability and efficiency of expression of K5Z genes depend on both long range chromosomal influences and on sequences in the transgene array.

Animals↗
PubMed2001

A cutaneous gene therapy approach to human leptin deficiencies: correction of the murine ob/ob phenotype using leptin-targeted keratinocyte grafts.

Leptin deficiency produces a phenotype of obesity, diabetes, and infertility in the ob/ob mouse. In humans, leptin deficiency occurs in some cases of congenital obesity and in lipodystrophic disorders characterized by reduced adipose tissue and insulin resistance. Cutaneous gene therapy is considered an attractive potential method to correct circulating protein deficiencies, since gene-transferred human keratinocytes can produce and secrete gene products with systemic action. However, no studies showing correction of a systemic defect have been reported. We report the successful correction of leptin deficiency using cutaneous gene therapy in the ob/ob mouse model. As a feasibility approach, skin explants from transgenic mice overexpressing leptin were grafted on immunodeficient ob/ob mice. One month later, recipient mice reached body weight values of lean animals. Other biochemical and clinical parameters were also normalized. In a second human gene therapy approach, a retroviral vector encoding both leptin and EGFP cDNAs was used to transduce HK and, epithelial grafts enriched in high leptin-producing HK were transplanted to immunosuppressed ob/ob mice. HK-derived leptin induced body weight reduction after a drop in blood glucose and food intake. Leptin replacement through genetically engineered HK grafts provides a valuable therapeutic alternative for permanent treatment of human leptin deficiency conditions.

Animals↗