Biomedical subjects

R Urbano

Publications and source records attributed to R Urbano.

17 recordsLinked to original sources

PubMed2001

Expression of p15(ink4b) gene during megakaryocytic differentiation of normal and myelodysplastic hematopoietic progenitors.

In myelodysplastic syndrome (MDS), the expression of the cyclin-dependent kinase inhibitor p15(ink4B) (p15) is frequently decreased because of the aberrant methylation of the gene promoter; p15 is normally up-regulated during megakaryocytic differentiation. It was hypothesized that p15 methylation and deregulation of gene expression contribute to defective megakaryocytopoiesis in patients with MDS. Here it is shown that the increasing autocrine production of TGF-beta1 stimulates megakaryocytic differentiation in normal CD34(+) cells and that p15 mediates, at least in part, this effect. This TGF-beta1-dependent pathway is altered in MDS CD34(+) progenitors because of p15 methylation. The demethylating agent 2-deoxyAZAcytidin can restore the normal demethylated state of the p15 gene and increase its expression. Nevertheless, MDS CD34(+) cells only poorly differentiate to the megakaryocytic lineage. These findings suggest that p15 methylation occurs in a neoplastic clone with a profound defect of cell proliferation, survival, and differentiation that cannot be overcome by using a demethylating drug.

Anemia, Refractory, with Excess of Blasts↗

PubMed2001

Clonal hemopoiesis and risk of thrombosis in young female patients with essential thrombocythemia.

OBJECTIVE: Several studies demonstrated a high prevalence of nonrandom X-chromosome inactivation pattern (X-CIP) in essential thrombocythemia (ET). This study explored the incidence of clonal hemopoiesis in myeloid precursors and endogenous erythroid colonies (EECs) in ET patients and its correlation with thrombotic manifestations. MATERIALS AND METHODS: Clonal analysis of hemopoiesis using X-CIP was performed in 40 female patients with ET. Median age was 40.5 years (range 20-64), and median platelet count at testing time was 700 x 10(9)/L (range 220-1300 x 10(9)/L). Patients older than 65 years were excluded to reduce age-related skewing. Clonality was assessed on neutrophils, platelets, EECs, and bone marrow CD34(+) cells. RESULTS: Eight (20%) of 40 patients developed thrombosis mainly at diagnosis. Clonal hemopoiesis was found in 17 (42.5%) patients, 15 (37.5%) had polyclonal hemopoiesis, and 8 (20%) were considered uninterpretable due to constitutive skewing. Clonality was confirmed on purified CD34(+) subpopulations from bone marrow, documenting that clonality does not appear lineage-restricted. There were no statistical differences in age at diagnosis, median platelet count at testing time, and length of follow-up. Thrombotic episodes were significantly more frequent in the monoclonal group (p = 0.04, Fisher exact test). CONCLUSIONS: Young female patients with ET exhibiting a clonal pattern of hemopoiesis by X-CIP analysis are at higher risk for thrombosis. X-CIP analysis may contribute to defining the individual risk leading to appropriate treatment. X-CIP will allow a correct diagnosis in patients with latent myeloproliferative disorders and thrombosis in unusual sites. Clonal hemopoiesis is easily recognized by X-CIP, but its applicability is limited to the female sex and is hampered by the presence of age-related or constitutive skewing.

Adult↗

PubMed2000

Expression of cyclin-dependent kinase inhibitor p15(INK4B) during normal and leukemic myeloid differentiation.

OBJECTIVE: Expression of the cyclin-dependent kinase inhibitor p15(INK4B) frequently is altered in myeloid malignancies. We previously demonstrated that p15(INK4B) is expressed in normal myeloid cells. The aim of this study was to investigate whether p15(INK4B) expression is restricted to the granulomonocytic lineage and to evaluate its modulation during normal and leukemic myeloid differentiation. MATERIALS AND METHODS: Normal CD34(+) cells were cultured in serum-free media to obtain granulomonocytic, erythroid, or megakaryocytic unilineage differentiation. NB4 promyelocytic cell line and fresh leukemic blasts from seven patients with acute promyelocytic leukemia were cultured with all-trans retinoic acid. At different times of culture, cell samples were collected to evaluate p15(INK4B) by semiquantitative reverse transcriptase polymerase chain reaction. RESULTS: p15(INK4B) mRNA was found during granulomonocytic and megakaryocytic, but not erythroid, differentiation. In the granulomonocytic lineage, p15(INK4B) was detectable when the majority of cells were at the promyelocytic stage and increased progressively in more mature elements. In the megakaryocytic lineage, p15(INK4B) was expressed in the early phase of differentiation, before megakaryoblasts had appeared, and was mantained throughout the time of culture. NB4 cell line and five of seven leukemic samples displayed undetectable or very low level of p15(INK4B) that rapidly increased during retinoic acid-induced differentiation. Two leukemic samples (both collected from two patients developing all-trans retinoic acid syndrome) showed high basal levels of p15(INK4B), which was not modified by retinoic acid treatment. CONCLUSIONS: p15(INK4B) upregulation occurs specifically during normal granulomonocytic and megakaryocytic commitment. In acute promyelocytic leukemic blasts, p15(INK4B), which is detectable at a very low level, is promptly increased by retinoic acid. In contrast, two acute promyelocytic leukemia samples obtained from patients who developed all-trans retinoic acid syndrome showed high basal levels of p15(INK4B) that did not increase further during all-trans retinoic acid-induced differentiation.

Antigens, CD34↗

PubMed1997

Long terminal repeat and nef gene variants of human immunodeficiency virus type 1 in perinatally infected long-term survivors and rapid progressors.

HIV-1 sequences from perinatally infected children were analyzed in the long terminal repeat (LTR) region and nef in order to investigate associations of viral variation and disease progression. Four long-term survivors who reached 10 years of age or older, and four rapid progressors who survived less than 2 years, participated in this study. LTR sequences of multiple independent viral variants from each individual were compared. No sequence pattern within the LTR consistently distinguished long-term survivors from rapid progressors or vice versa. Deletions and insertions within transcription factor binding sites of the LTR and nef ranging from 8 to 341 bp were found in viral variants from the eldest long-term survivor (LTS047). These deletions and duplications may be associated with the survival of LTS047 via an unknown mechanism. Among all children in this study, the sites in the untranslated region (NF-kappaB, SP1, and TATA box) were more conserved than the sites in the nef/LTR overlap region (NFAT, purine-rich region, USF, TCF1alpha), reflecting the importance of the sites in the untranslated region for viral replication. A mutation in the E box motif within the USF site among the sequences from a long-term survivor (LTS113) is predicted to disrupt protein binding and may be associated with slow disease progression. Mutations of the SP1-III site in a rapid progressor (RP056) indicate that this site is not necessary for rapid disease progression.

Amino Acid Sequence↗

PubMed1997

Development of precursors to speech in infants exposed to two languages.

The study of bilingualism has often focused on two contradictory possibilities: that the learning of two languages may produce deficits of performance in each language by comparison with performance of monolingual individuals, or on the contrary, that the learning of two languages may produce linguistic or cognitive advantages with regard to the monolingual learning experience. The work reported here addressed the possibility that the very early bilingual experience of infancy may affect the unfolding of vocal precursors to speech. The results of longitudinal research with 73 infants aged 0;4 to 1;6 in monolingual and bilingual environments provided no support for either a bilingual deficit hypothesis nor for its opposite, a bilingual advantage hypothesis. Infants reared in bilingual and monolingual environments manifested similar ages of onset for canonical babbling (production of well-formed syllables), an event known to be fundamentally related to speech development. Further, quantitative measures of vocal performance (proportion of usage of well-formed syllables and vowel-like sounds) showed additional similarities between monolingual and bilingual infants. The similarities applied to infants of middle and low socio-economic status and to infants that were born at term or prematurely. The results suggest that vocal development in the first year of life is robust with respect to conditions of rearing. The biological foundations of speech appear to be such as to resist modifications in the natural schedule of vocal development.

Child Language↗

PubMed1995

Influence of host genotype on progression to acquired immunodeficiency syndrome among children infected with human immunodeficiency virus type 1.

OBJECTIVE: To study the role of host genotype in pediatric infection with human immunodeficiency virus type 1 (HIV-1) and progression to acquired immunodeficiency syndrome (AIDS). METHODS: Human leukocyte antigen (HLA) class II and complement C4 genotypes were determined by means of molecular genetic techniques for 243 black children born to HIV-1-infected mothers in New York City and San Francisco. Survival, cumulative incidences of opportunistic infections and encephalopathy, and rates of CD4+ T cell decline were compared in children of different genotypes. RESULTS: Among HIV-1-infected children, the HLA-DR3 haplotype (DRB1*0301-DQA1*0501-DQB1*0201) was associated with increased incidence of encephalopathy, faster rate of CD4+ cell decline, and death before 2 years of age. Deletion of the C4A gene was independently associated with increased incidences of encephalopathy and early death. DPB1*0101 was associated with survival to at least 2 years of age. The presence of DQB1*0604 was associated with increased risk of HIV infection. CONCLUSIONS: These results are consistent with previously reported associations between HLA genotypes and faster progression to AIDS among HIV-infected adults. The DR3 haplotype and C4A deletion may reflect the same underlying mechanism of susceptibility in that the DR3 haplotype is in linkage disequilibrium with other C4A null alleles. In addition, the class II locus DPB1 may have an independent effect on survival.

Acquired Immunodeficiency Syndrome↗

PubMed1994

Speech-like vocalizations in infancy: an evaluation of potential risk factors.

This work reports longitudinal evaluation of the speech-like vocal development of infants born at risk due to prematurity or low socio-economic status (SES) and infants not subject to such risk. Twenty infants were preterm (10 of low SES) and 33 were full term (16 of low SES), and all were studied from 0;4 through 1;6. The study provides the indication that at-risk infants are not generally delayed in the ability to produce well-formed speech-like sounds as indicated in tape-recorded vocal samples. At the same time, premature infants show a tendency to produce well-formed syllables less consistently than full terms after the point at which parents and laboratory personnel note the onset of the canonical babbling stage (the point after which well-formed syllables are well established in the infant vocal repertoires). Further, even though low SES infants produce well-formed speech-like structures on schedule, they show a reliably lower tendency to vocalize in general, as reflected by fewer utterances per minute in recorded samples.

Female↗

PubMed1993

Perception of the stop/glide contrast in infancy.

Much of the published research in infant speech perception has emphasized how well infants have done with a number of speech contrasts, and have noted similarities in pattern of discrimination of adults and infants. Often it has been suggested that infants begin life with the ability to perceive any speech contrast, and that the process of acquiring a language involves inhibition of the ability to perceive contrasts not present in the target language. Indeed some studies have shown infants able to discriminate contrasts on which adults fail if the contrasts are not drawn from the native language of the adults. Other studies, however, have suggested that infants may not always be so perceptually capable. The present work focusses on the stop-glide contrast. The results are inconsistent with the prevalent view and with previously reported studies on the perception of the stop-glide contrast by infants. The results indicate that in a vigilance paradigm adapted for both infant and adult testing, infants perform poorly on the contrasts when compared with adults. Furthermore the pattern of relative perception observed in the adults on stimuli with long or short vowels is quite unlike that of the infants. It is concluded that much work remains in order to evaluate the relative performance of infants and adults in speech perception, since it appears that changes in experimental paradigm or particular stimulus parameters may affect outcomes in fundamental ways.

Acoustic Stimulation↗

PubMed1991

Optimization of automated hearing test algorithms: simulations using an infant response model.

Computer simulation was used to evaluate several parameters of an automated hearing test algorithm in an attempt to optimize the algorithm for accuracy and efficiency. An infant response model was developed to guide the simulations. Test parameters of interest were starting intensity and stopping rule and their interaction with a measure that is thought to emulate infant reliability, probability of task orientation. Results indicated that stopping rule, within the ranges investigated, had little effect on accuracy but had major impact on efficiency. Starting intensity interacted with the hearing status of pseudosubjects in influencing accuracy. Accuracy was most influenced by probability of task orientation. The simulated test data are compared to data from infants and young children in the accompanying article so that the response model can be evaluated.

Algorithms↗

PubMed1991

Optimization of automated hearing test algorithms: a comparison of data from simulations and young children.

A five-up, five-down automated staircase procedure was used to explore the effects of variable starting and stopping rules as they interact with infant behavior in influencing the accuracy and efficiency of infant auditory threshold testing. Results from 146 infants were compared to results from computer simulations (see accompanying article) in order to evaluate an infant response model used in the simulations. Results indicate that the automated procedure successfully discriminated between infants with normal versus abnormal tympanograms. In addition, the model accurately predicted infant results in terms of the effects of starting and stopping rules. The model was less useful in predicting the relationship between minimum response levels and false positive rates.

Algorithms↗

PubMed1991

The stop/glide boundary shift: modelling perceptual data.

Research in speech perception has suggested that listeners often adjust category boundary locations for differing contexts. The stop/glide (e.g.,/ba/vs./wa/) boundary shift occurring with changes in syllable duration has been interpreted as reflecting 'rate normalization' by some, whereas others have suggested an auditory basis for the shift. Clarification of both the causes and the effects of the stop/glide shift is being sought through experimentation intended to expand our knowledge of variations in the shift across different experimental treatments. The present study extends research on the stop/glide shift by (1) showing that the shift is not an artifact of a particular stimulus pattern that had been present in all the previous studies of the effect, (2) further demonstrating the nonlinear character of the identification shift, (3) providing additional evidence of the role of presentation format (mixed vs. blocked) in the identification shift, and (4) exploring boundary locations in various discrimination paradigms. The complex outcomes of the studies reported here as well as a variety of previous results are interpreted as compatible with expanded versions of the durational contrast hypothesis. Two versions are considered, one in which the shift is seen as due to a mechanism of contrastive perception that applies to events of comparable duration, and one in which the shift is seen as a perceptual error that occurs when the auditory system attempts to track frequency trajectories that change (i.e., pivot) over time.

Adult↗

PubMed1989

The effects of vocoder filter configuration on tactual perception of speech.

Perception of synthetic speech continua through the sense of touch and audition was compared utilizing a 32-channel spectrally-oriented electrocutaneous vocoder display and standard auditory psychophysical procedures. Perception of a consonantal and a vocalic continuum was evaluated utilizing three vocoder filter configurations: logarithmic, linear, and average (geometric mean of logarithmic and linear). Results indicated a close correspondence between tactual and auditory discrimination and identification for the vowel (/a/-/e/) and the consonant (/sta/-/sa/) continuum regardless of the filter characteristics.

Deafness↗

PubMed1989

Conflicting and cooperating cues: perception of cues to final consonant voicing by infants and adults.

Three experiments were conducted to ascertain the relative salience of two cues for final consonant voicing in infants and adults. Experiment 1 was designed to investigate infant perception of periodicity of burst, vowel duration, and the two cues combined in a cooperating pattern. Experiment 2 was designed to examine infant perception of these same cues but in a conflicting pattern, that is, with extended duration associated with the voiceless final plosive. Experiment 3 examined perception of the stimuli from Experiments 1 and 2 with adult subjects. Results indicate that in both adults and infants combined cues facilitate discrimination of the phonemic contrast regardless of whether the cues cooperate or conflict. The three experiments taken together do not support a phonetic interpretation of conflicting/cooperating cues for the perception of final stop consonant voicing. Potential psychoacoustic explanations are discussed.

Adult↗

PubMed1988

Similarities between tactual and auditory speech perception.

Perception of synthetic speech continua through the sense of touch and audition was compared utilizing a 32-channel spectrally oriented electrocutaneous display and standard auditory psychophysical procedures. Results indicated a close correspondence between tactual and auditory discrimination and identification for a vowel (/a/-/e/) and a consonant (/sta/-/sa/) continuum. These results suggest that at least some aspects of speech perception are amodal.

Humans↗

PubMed1984

Public school satisfaction with interdisciplinary services.

Representatives from local, regional, and state educational agencies throughout the country were surveyed to determine their satisfaction with services provided by University Affiliated Programs (UAPs). Sixty-eight respondents from 26 states and the District of Columbia returned questionnaires indicating their assessment of UAP services. Overall results showed highly positive ratings regarding access to UAP services, interdisciplinary evaluations, comprehensiveness, and relevancy of written reports and in-service training activities.

Consumer Behavior↗

PubMed1982

Status of interagency cooperation between interdisciplinary clinics or hospitals and the public schools.

Since public schools are now mandated to provide a large and varied range of clinical services to handicapped school children, a survey was conducted of 26 interdisciplinary UAF clinics and hospitals in regard to the types of services which they offer to public school children and the extent in which coordination of such services has been developed. Results suggest that diagnosis of evaluation is the primary reason for referral but that a wide variety of community outreach services are both requested by the schools and offered by interdisciplinary hospital and clinic staff. These services are described and the implications for future interagency cooperation are discussed.

Child↗

PubMed1980

Identifying children with school learning and behavior problems served by interdisciplinary clinics and hospitals.

Questionnaires were sent to interdisciplinary UAF programs across the country to assess the types of handicapped school children who were receiving services at their facilities. A return rate of 65 percent was obtained and the total sample of children was 2088. Results indicated that a wide variety of ages and handicapping conditions were reported. Referral sources and services rendered were analyzed, and implications for cooperation with public school personnel were discussed.

Adolescent↗