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Biomedical subjects

H Suarez

Publications and source records attributed to H Suarez.

At least 19 recordsLinked to original sources
PubMed2003

Changes in postural control parameters after vestibular rehabilitation in patients with central vestibular disorders.

OBJECTIVE: The aim of this study was to determine postural responses before and after a vestibular rehabilitation program (VRP) in 14 patients with central vestibular disorders (CVD). MATERIAL AND METHODS: The confidence ellipse (CE) of the center of pressure distribution area and the sway velocity (SV) were the parameters used for the quantitative assessment of postural control (PC). These two parameters were analyzed before and after a VRP for two visual conditions. Behavioral postural responses were studied by means of the time-frequency scalogram using wavelets and the sway frequency content was measured in arbitrary units of energy density. RESULTS: Ten patients showed a significant decrease in the CE and SV after the rehabilitative treatment, thus improving their PC. Seven of these patients were assessed again after a period of 12 +/- 5 months, during which they had not received any physical training. All of them showed increases in the CE and SV, indicating an impairment of PC. CONCLUSIONS: Many CVD patients damage the neural mechanisms involved in retaining the plastic changes in the PC parameters after rehabilitative treatment. Continuation of training may be necessary in order to maintain the improvement in PC obtained with a VRP.

Adaptation, Ocular↗
PubMed2001

Papillary thyroid carcinoma: 6 cases from 2 families with associated lymphocytic thyroiditis harbouring RET/PTC rearrangements.

Familial papillary thyroid carcinoma (PTC) is a well recognized disease. However, genetic predisposition to familial PTC is rare and the molecular alterations at the origin of the pathology are unknown. The association between PTC and lymphocytic thyroiditis (LT) has been reported recently. We communicate here 6 cases of PTC associated with LT in 2 unrelated families. PTC was diagnosed on classical nuclear and architectural criteria. It was bilateral in 5 cases. Architecture was equally distributed between typical PTC and its follicular variant. LT was present in variable degrees, including in 4 cases, oncocytic metaplasia. Using the RT-PCR technique, we observed a RET/PTC rearrangement in the carcinomatous areas of patients of both families: PTC1 in family 1 and PTC3 in family 2 and a RET/PTC rearrangement in non-malignant thyroid tissue with LT in family 2. The RET/PTC band was weaker or absent in pure LT areas. Furthermore, using a polyclonal ret antibody, an apical or a diffuse cytoplasmic ret onc protein immunolabelling was observed in the three patients with RET/PTC1 rearrangement and in the three patients with RET/PTC3 rearrangement. In conclusion our data: (1) show the presence of a RET/PTC 1 or 3 rearrangement (depending on the family) together with a variable expression of ret protein in all the PTCs; (2) suggest that the molecular event at the origin of the PTCs seems to be particular to each one of the studied families; and (3) confirm that the ret proto-oncogene activating rearrangement(s) is an early event in the thyroid tumorigenic process and that it can be observed in association with LT.

Adenoma↗
PubMed2001

Auditory learning and adaptation after cochlear implantation: a preliminary study of discrimination and labeling of vowel sounds by cochlear implant users.

This study examined two possible reasons underlying longitudinal increases in vowel identification by cochlear implant users: improved labeling of vowel sounds and improved electrode discrimination. The Multidimensional Phoneme Identification (MPI) model was used to obtain ceiling estimates of vowel identification for each subject, given his/her electrode discrimination skills. Vowel identification scores were initially lower than the ceiling estimates, but they gradually approached them over the first few months post-implant. Taken together, the present results suggest that improved labeling is the main mechanism explaining post-implant increases in vowel identification.

Adaptation, Psychological↗
PubMed2000

Postural behaviour responses to visual stimulation in patients with vestibular disorders.

Patients with different vestibular disorders exhibit changes in postural behaviour when they receive visual stimuli, reproducing environmental stimulation. Postural control was studied using an AMTI Accusway platform, measuring the confidential ellipse (CE) and sway velocity (SV). Postural responses were recorded according to the following stimulation paradigm: i) without specific stimuli; ii) smooth pursuit with pure sinusoids of 0.2 Hz (foveal stimulation); and iii) optokinetic stimulation (retinal stimuli). Patients with central vestibular disorders (CVD), cerebellar damage and unilateral peripheral vestibular lesions (UPVL) in asymptomatic periods were studied. A group of normal subjects was studied as control. Signal processing was done with a scalogram by wavelets in order to observe the relation between time and frequency in postural control. While patients with CVD and cerebellar disease showed a significant increase in CE and SV in the three conditions of the paradigm compared to the normal group, the patients with UPVL showed no change. Wavelets processing showed that the main sway occurs in the Y axis (antero-posterior) and below at 0.4 Hz in normal subjects, while the CVD and cerebellar patients showed sway frequencies in both the X and Y axes. The clinical implications of these findings are discussed.

Adult↗
PubMed1995

Modeling direction selectivity of simple cells in striate visual cortex within the framework of the canonical microcircuit.

Nearly all models of direction selectivity (DS) in visual cortex are based on feedforward connection schemes, where geniculate input provides all excitatory synaptic input to both pyramidal and inhibitory neurons. Feedforward inhibition then suppresses feedforward excitation for nonoptimal stimuli. Anatomically, however, the majority of asymmetric, excitatory, synaptic contacts onto cortical cells is provided by other cortical neurons, as embodied in the Canonical Microcircuit of Douglas and Martin (1991). In this view, weak geniculate input is strongly amplified in the preferred direction by the action of intracortical excitatory connections, while in the null direction inhibition reduces geniculate-induced excitation. We investigate analytically and through biologically realistic computer simulations the functioning of a cortical network based on massive excitatory, cortico-cortical feedback. The behavior of this network is compared to physiological data as well as to the behavior of a purely feedforward model of DS based on nonlagged input. Our model explains a number of puzzling features of direction selective simple cells, including the small somatic input conductance changes that have been measured experimentally during stimulation in the null direction, and the persistence of DS while fully blocking inhibition in a single cell. Although the operation at the heart of our network is amplification, the network passes the linearity test of (Jagadeesh et al., 1993). We make specific predictions concerning the effect of selective blockade of cortical inhibition on the velocity-response curve.

Animals↗
PubMed1993

High mutation frequency in ras genes of skin tumors isolated from DNA repair deficient xeroderma pigmentosum patients.

Xeroderma pigmentosum (XP) patients are clinically characterized by a very high incidence of skin cancers on exposed skin, at an early age. XP cells in vitro are strongly deficient in excision-repair and highly mutagenized by UV light. We were, therefore, interested in measuring mutation frequency and in determining mutation spectra in patients' tumors exposed to UV lesions. We chose to look at oncogene activation in skin tumors with the idea that more mutations, particularly of the ras gene family, would be found in XP tumors where lesions remain unrepaired compared to normal individuals. Our results clearly show that more than a 2-fold significantly higher mutation frequency (50%) of the ras genes was found in XP in contrast to control tumors (22%). The majority of the mutations were found at codon 12 of all three ras genes with a preponderance for N-ras in XP samples. The mutation spectra indicate that all mutations found were located opposite pyrimidine-pyrimidine sequences which represent a hot spot for UV-induced DNA lesions. Most of the mutations were of the type expected from studies performed in vitro with model systems. This high mutation frequency in XP was accompanied by a very high level of Ha-ras and c-myc gene amplification and rearrangement. All these data are consistent with a fundamental role of unrepaired UV-induced DNA lesions as an initiating event in human skin tumors on exposed parts of the body.

Base Sequence↗
PubMed1992

Expression of the interleukin-2 receptor on human fibroblasts and its biological significance.

In this study, we have investigated the expression of the alpha and beta chains of the IL-2 receptor (IL-2R alpha, IL-2R beta) both at the membrane and at transcriptional levels during the lifespan of human embryonic fibroblasts. Here we show that the mAbs IOT14 and MIK beta 1 directed against the IL-2 binding sites of the IL-2R alpha and IL-2R beta respectively, stain human embryonic fibroblasts early in their life span. Data from [125I]rIL2 cross-linking experiments show the simultaneous expression of two IL-2 binding peptides of 70 and 55 kDa respectively on embryonic young fibroblasts as on lymphoid activated cells. The p55 and the p70 IL-2 binding peptides are shown to be specific for the IL-2R alpha and to the IL-2R beta by the finding that these bands are abolished by excess amounts of cold IL-2 and mAbs directed against the IL-2 binding sites of the alpha and beta chains. Scatchard analysis after [125I]IL-2 labelling shows the presence of both high affinity (150 sites with a Kd of 147 pM) and low affinity (1100 sites with a Kd of 4 nM) IL-2 binding sites. Northern blot and dot blot analysis show the presence of specific transcripts for the IL-2R alpha and IL-2R beta genes in early passaged fibroblasts. By contrast, in senescent cultures, only the IL-2R beta transcript were detected. Finally, IL-2 at low concentrations (36 pM) down modulates the level of the intercellular adhesion molecule ICAM-1 in young but not in senescent cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Adhesion Molecules↗
PubMed1989

N-ras dependent revertant phenotype in human HT1080 fibrosarcoma cells is associated with loss of proliferation within normal tissues and expression of an adult membrane antigenic phenotype.

To investigate how the activated N-ras oncogene contributes to the tumorigenic potential of malignant human fibrosarcoma HT1080 cells we analysed the behavior of the parental cell line and of two flat revertants (1c and 10a) in an organ culture assay for invasion. In this assay the two revertants retain the ability of HT1080 cells to migrate within the chick cardiac muscle but lose the capacity to proliferate and to replace the normal tissue. Moreover the reversion of tumorigenic potential is associated with an evolution from an oncofoetal membrane antigenic pattern towards expression of a normal adult phenotype. Both the 4F2 antigen, which is implicated in the control of HT1080 cell proliferation, and heterodimers of the two chains (alpha and beta) of the IL2 receptor (IL2-R) are expressed in embryonic and HT1080 cells, but not in normal adult fibroblasts or in the revertant cell lines. For the first time in a non-lymphoid environment, we have detected a complex between the two IL2-R chains, together with a new species of mRNA (2.8 kB) from the IL2-R alpha gene. The behavior of these membrane markers strengthens the hypothesis that HT1080 cells may represent a block in the differentiation pathway of fibroblastic cells.

Antigens, Surface↗
PubMed1988

Differential sensitivity to pertussis toxin of 3T3 cells transformed with different oncogenes.

Pertussis toxin (PT), which blocks the activity of several G-proteins, has been found to exert a marked inhibitory effect on the DNA synthesis induced in 3T3 cells by serum or growth factors. 3T3 cells transformed with human c-ras oncogenes (Ha-ras, Ki-ras, N-ras) or with src, an oncogene coding for a protein kinase, have lost sensitivity to growth control by PT, even though substrates for PT can still be ADP-ribosylated in vivo. In contrast, 3T3 cells transformed with the SV40 virus behave like normal untransformed cells with respect to the ability of PT to decrease their growth rate. Oncogenes can thus likely be classified either as 'responders' or 'non-responders' to PT.

Animals↗
PubMed1988

Both N-ras and c-myc are activated in the SHAC human stomach fibrosarcoma cell line.

A transforming N-ras gene was isolated from the SHAC human stomach fibrosarcoma cell line. A single-point mutation resulting in the substitution of histidine for glutamine at codon 61 was found in the SHAC transforming allele. The N-ras gene is overexpressed in the tumor cells and transformant cells. The N-ras p21 product was studied by immunoprecipitation and showed no alteration in mobility as compared to the normal p21 protein. The c-myc gene is amplified and overexpressed in these cells. This report gives evidence that an amplified c-myc and a mutated N-ras gene are both present in this tumor cell line and provides support for the idea that co-operation of at least 2 activated cellular oncogenes is required for carcinogenesis.

Animals↗
PubMed1988

Human fibroblasts from cancer patients: lifespan and transformed phenotype in vitro and role of mesenchyme in vivo.

Human fibroblasts cultured in vitro can exhibit a different potential number of population doublings. In normal donors, the average number of population doublings is inversely related to the donor's age. An increased growth potential was detected in skin fibroblasts from breast cancer patients, independently of the donor's age. These cells responded in an abnormal way to 3 biological parameters: (1) colony formation in semisolid medium; (2) colony formation on monolayers of normal human epithelial cells; and (3) increase of saturation densities in overcrowded culture conditions. A third of these cultures, as well as skin fibroblasts from other cancer patients, at the plateau phase of growth exhibited a significant percentage of cells still synthesizing DNA. Exposure to overcrowding, limited in time, caused the selection of a cell subset which displayed new biological, biochemical and functional properties commonly found in transformed cells. The abnormal in vitro behavior of skin fibroblasts from breast cancer patients does not seem to be associated with the expression of oncofetal membrane markers (4F2, IL2 receptor) while the fibroblasts from patients with the adenomatosis of the colon and rectum (ACR) syndrome expressed the 4F2 antigen. This is the first time that the IL2 receptor is found on non-hematopoietic cells. Fibroblastic cells with abnormal characteristics, which may also present a decreased efficiency in organizing a primitive fibrin matrix, could represent in vivo an anarchistic milieu, favoring disturbed epithelial-stromal interactions and the emergence of the less structured tumor stromatic tissue.

Age Factors↗
PubMed1988

Susceptibility of Xeroderma pigmentosum cells to transformation with oncogenes.

Oncogenes capable of transforming 3T3-Vill cells were not detected in 'normal' Xeroderma pigmentosum (XP) fibroblasts but were detected in two out of six XP epitheliomas. Preliminary results concerning the transfection of 'normal' XP fibroblasts with activated ras genes seem to indicate that these cells are as resistant as the healthy controls to the transforming action of the group II oncogenes. However, after transfection with v-myb oncogene in XP fibroblasts several cellular clones have been isolated showing some new phenotypic characteristics.

Cell Line↗
PubMed1986

Evolution in the structure and distribution of 4F2-antigen from the oncofetal to the adult phenotype of human fibroblasts.

The monoclonal antibody (MAb) 4F2 defines an oncofetal antigen in human fibroblastic cells. Two-dimensional electrophoretic analysis reveals that tumor cell lines from mesenchymal tissues co-express two or more heavy-chain molecular variants of the antigen whereas the light subunit (41 kDa) is not affected. Among normal cells, only embryonic and newborn fibroblasts (from donors up to 20 days after birth) clearly co-express two distinct molecular forms of the heavy chain with MW of 85 and 75 kDa, respectively. Cells derived from 3-month-old donors express detectable amounts of the 85 kDA but only faint traces of the 75 kDa subunit, while fibroblastic cells derived from donors older than 3 months seem to express only the 85 kDa subunit. Immunofluorescence analysis performed on adherent living cells shows that, in the first months after birth, there is a gradual evolution from the oncofetal to the adult phenotype also in the cell distribution of the 4F2. This evolution is reflected by a progressive disappearance of the 4F2 antigen from the cell membrane becoming, in adult normal cells, inaccessible to anti-4F2 MAb. The existence of different molecular forms and different membrane positions of the 4F2 antigen could facilitate surveillance of morphological and structural changes in the evolution of human fibroblastic cells during the developmental process and neoplastic transformation.

Adult↗
PubMed1985

Analysis of the expression of the 4F2 surface antigen in normal and neoplastic fibroblastic human cells of embryonic and adult origin.

4F2 monoclonal antibody recognizes a 120-kD glycoprotein on the surface of human spread fibroblastic cells of embryonic and neoplastic origin, but it does not bind to normal spread adult fibroblasts. Flow cytometric analysis reveals that human adult fibroblasts become 4F2-positive when they are analyzed as round-shaped cells; this means that, in normal adult cells, 4F2 antigen behaves as a cryptic molecule. Thus, the basic difference between embryonic, neoplastic and normal adult cells consists in a different organization in the architecture of the cell membrane, since in embryonic and neoplastic cells there is a continuous expression of the 4F2 antigen independently of the cell shape and cell cycle phase. Quantitative flow cytometry shows that the mean surface density (MSD) of the 4F2 antigen 1, does not vary as a function of the cell cycle; 2, is inversely related to cell size and "metabolic time". This suggests that at the plateau phase the surface organization of G1 resting cells changes as a function of the number of days spent in culture; and 3, sarcoma and SV40-transformed cells show significantly increased MSD levels of the 4F2 antigen in comparison with normal cells of similar size. Electrophoretic analysis under reducing conditions confirms the quantitative differences in the expression of the 4F2 antigen described with the cell sorter. It also reveals, in a way different from that previously found with lymphoid cells, the coexistence of two molecules (85 and 73 kD) in the heavy chain regions. The 73 kD is, however, much more strongly expressed in the fibrosarcoma than in the embryonic cells. Finally, it shows that 4F2 antigen is a very useful tool for studying the organization and the structure of the cell membrane of human fibroblasts and can provide new insights to understand better the developmental and transformation processes.

Antibodies, Monoclonal↗
PubMed1985

Epikeratophakia for myopia correction.

Epikeratophakia is based on the principles of the Barraquer refractive procedures, with modifications that simplify the surgical technique and eliminate the use of the microkeratome by placing the donor corneal tissue lens on the anterior surface of the cornea. Procedures developed to permit freeze-drying the preshaped lens for storage enable these lenses to be obtained from a central source, freeing the surgeon from the complexities of the computer and the cryolathe. The correction of theoretically unlimited amounts of myopia is possible with these lenses. In 12 eyes that underwent the final epikeratophakia procedure, the average desired correction achieved was 98%.

Cornea↗
PubMed1984

4F2 monoclonal antibody recognizes a surface antigen on spread human fibroblasts of embryonic but not of adult origin.

The 4F2 monoclonal antibody (mAb) has been shown to recognize a 120-kilodalton glycoprotein expressed on the cell surface of human peripheral blood monocytes, activated (but not resting) T or B cells, and T and B lymphoblastoid cell lines. In this report we show that 4F2 mAb specifically binds to the surface of adherent human embryonic fibroblasts but fails to bind to normal adult fibroblasts. Moreover, 4F2 antigen was expressed on sarcoma-derived or SV40-transformed adult fibroblastic cells. Finally, addition of 4F2 mAb inhibited the growth of cultured HT-1080 fibrosarcoma cell line, but had no inhibitory effect on various embryonic and adult normal or transformed fibroblasts.

Animals↗
PubMed1981

Chromosomes involved in production of infectious SV40 particles in mouse/SV40-transformed Chinese hamster cell hybrids.

The clone 6d hybrid, capable of expressing the virus-specific T-antigen but unable to produce infectious virus particles after superinfection, presented a complete mouse (3T3-4E) chromosome complement and a significant loss of Chinese hamster (CHK/SVLP AG) chromosomes. Similar properties were displayed by a BUdR-resistant derivative of the Cl 6d hybrid (Cl 6d.6BU). Three independent superhybrid clones (CL 10B, Cl 10C, Cl 11A) isolated after backcross of the Cl 6d.6BU hybrid with a nontransformed Chinese hamster kidney cell line (CHK/AG) were able to produce infectious SV40 virus. In spite of the loss of mouse chromosomes, there was no significant difference in the average number of chromosomes between the Cl 6d.6BU and the superhybrid clones. Thus, the Chinese hamster chromosomes seemed to compensate for the loss of the mouse chromosomes. Although the effect of Chinese hamster chromosomes cannot be totally disregarded, our data suggested a positive correlation between the inability to produce infectious SV40 and the presence of certain mouse chromosomes.

Animals↗