Downregulation of E-cadherin in pluripotent stem cells triggers partial EMT.

Epithelial to mesenchymal transition (EMT) is a critical cellular process that has been well characterized during embryonic development and cancer metastasis and it also is implicated in several physiological and pathological events including embryonic stem cell differentiation. During early stages of differentiation, human embryonic stem cells pass through EMT where deeper morphological, molecular and biochemical changes occur. Though initially considered as a decision between two states, EMT process is now regarded as a fluid transition where cells exist on a spectrum of intermediate states. In this work, using a CRISPR interference system in human embryonic stem cells, we describe a molecular characterization of the effects of downregulation of E-cadherin, one of the main initiation events of EMT, as a unique start signal. Our results suggest that the decrease and delocalization of E-cadherin causes an incomplete EMT where cells retain their undifferentiated state while expressing several characteristics of a mesenchymal-like phenotype. Namely, we found that E-cadherin downregulation induces SNAI1 and SNAI2 upregulation, promotes MALAT1 and LINC-ROR downregulation, modulates the expression of tight junction occludin 1 and gap junction connexin 43, increases human embryonic stem cells migratory capacity and delocalize ß-catenin. Altogether, we believe our results provide a useful tool to model the molecular events of an unstable intermediate state and further identify multiple layers of molecular changes that occur during partial EMT.

Human placenta mitochondrial aromatase--fact or artifact.

The suggestion has been made that the aromatase system from human placenta converting testosterone to estradiol-17 beta is localized to some extent in the mitochondrial fraction in addition to its microsomal origin. By comparing the characteristics of the "mitochondrial" aromatase with certain particularities of other mitochondrial or microsomal enzymes, especially those functioning in steroid hydroxylation, the conclusion has been reached that the mitochondrial and the microsomal aromatases are one and the same. Thus, in response to ultrasound treatment and in response to the addition of specific cofactors, the mitochondrial aromatase showed all the characteristics attributed to microsomal enzymes and was indistinguishable from the microsomal aromatase.

Manic-depressive illness in children: treatment with lithium carbonate.

A behavior questionnaire was used retrospectively in 21 manic-depressive children to quantitate manic-depressive behaviors before and after treatment with lithium carbonate. The study children were matched with 21 control children for age, race, sex, and socioeconomic status. The study children had significantly more seizures, relatives with psychotic disorders, allergies, food sensitivities, headaches, and abnormal behaviors in all categories measured. During treatment, manic-depressive children had a statistically significant reduction in disturbed behavior. This behavior, however, was still significantly more disturbed than normal control children.

Changes in communication apprehension, satisfaction, and competence in foreign dialect and stuttering clients.

This study examined changes in predispositions toward communication over the course of therapy. Results indicated that both foreign dialect and stuttering clients had significantly lower levels of communication apprehension and higher levels of communication competence after 3 1/2 months of their respective therapies; each client group also demonstrated significant improvements in the speech parameters upon which treatment focused. Discussion focused on the utility of using communication measures with clinical populations.

Development of the object permanence concept in cleft lip and palate and noncleft lip and palate infants.

Studies of language acquisition in cleft lip and palate infants have not investigated the development of specific cognitive concepts, such as object permanence, which may be related to early linguistic skills. This study obtained comparative data on the development of the object permanence concept in cleft lip and palate and noncleft lip and palate infants to determine whether there were significant differences in rate or sequence of development. Infants were tested for the object permanence concept from 12 through 18 months of age. Results revealed significant improvement in all infants' scores with age, indicating progressive development of the concept. Further, while scores were not significantly different between the cleft lip and palate groups, scores for these groups were significantly better than scores for noncleft lip and palate infants. Superior performance of the cleft lip and palate infants may have resulted from increased environmental stimulation provided by their parents. Implications for intervention and future research in this area are presented.

Development of infants and toddlers with clefts from birth to three years of age.

OBJECTIVE: The purpose of this study was to use caregiver report measures to describe the developmental status of infants and toddlers with clefts. METHOD: Developmental assessment data were obtained on 186 infants and toddlers with cleft lip (n = 48), cleft palate (n = 46), and cleft lip/palate (n = 92) at one of the following age categories: 5 months (n = 47), 13 months (n = 46), 25 months (n = 47), and 36 months (n = 46). Developmental assessment measures used were the Kent Infant Developmental Scale and the Minnesota Child Development Inventory, both caregiver reports. Data were analyzed in separate 2-between ANOVAs (age x cleft type) for each developmental domain according to developmental assessment measure. Further, results were examined relative to the normative sample. RESULTS: The ANOVA results indicated that at 5 months, lower motor and self-help developmental quotients (DQs) were evident compared to the 13-month-old level. When compared to the normative sample, the 5-month-old infants exhibited 'at-risk/delayed' development on the motor, self-help, and cognitive domains, and as reflected on their full-scale scores, depending on the cleft type. Infants at 13 and 25 months were within normal limits in all developmental domains, with the exception of the 13-month-old infants with cleft palate, who demonstrate 'at-risk' development in the motor domain. At 36 months of age, all toddlers demonstrated significantly lower developmental performance in the fine motor, gross motor, and expressive language domain compared to the 25-month-old toddlers. Toddlers with cleft palate exhibit 'at-risk/delayed' development in the expressive language domain at 36 months. CONCLUSION: Data are discussed relative to the events surrounding team management of clefts, including surgery, middle-ear problems, and feeding difficulty.

A roentgencephalometric investigation of the effect of adenoid removal upon selected measures of velopharyngeal function.

Pre-and postoperative lateral x-rays were taken of 15 candidates for adenoid removal, ranging in age from four to seven years. Cephalometric measurements were taken during rest and during function (/s/). The postoperative group acquired pharyngeal dimensions of C.P.I. proportions as a result of adenoid removal. However, all subjects achieved velopharyngeal closure and displayd no hypernasality following this surgical procedure, indicating success in terms of speech. The success in their adaptation can be attributed to the following: 1) increased velar mobility; 2) increased height of velopharyngeal closure; 3) increased percent of velar stretch; and 4) anterior movement of the posterior pharyngeal wall when amount of velopharyngeal contact became tenuous. The normal velopharyngeal mechanism has the capacity to successfully overcome the imbalance between pharyngeal dimensions and velar length caused by adenoid removal. The normal mechanism overcomes this imbalance by means of compensations, some of which are typical of the inadequate mechanism.

Nasometric sensitivity and specificity: a cross-dialect and cross-culture study.

A series of 514 patients seen at three clinics in the United States and Spain were evaluated using clinical judgments of hypernasality, and nasometric assessment of oral-nasal resonance balance. Data from the nasometer were obtained while patients read a passage devoid of nasal consonants. Across all subjects, the Pearson correlation coefficient between the clinical and instrumental measures was 0.78. Prediction analyses revealed that maximum efficiency was obtained using a somewhat different threshold nasalance value for each of the three patient samples. When all 514 subjects were investigated as a single group, a threshold nasalance score of 28 was found to optimize identification of patients with and without clinically significant hypernasality. In that analysis, a sensitivity of 0.87, a specificity of 0.86 and an overall efficiency of 0.87 was obtained. The clinical relevance of these findings is discussed.

Treatment of cleft palate associated with Robin sequence: appraisal of risk factors.

Mandibular hypoplasia, airway obstruction, and a typical wide U-shaped cleft palate comprise the Robin sequence. Although much has been written regarding the treatment of these patients in the neonatal period, the literature reveals little information regarding later care of the cleft palate in these patients. The purpose of this study is to examine patients with the Robin sequence and evaluate the risk of postsurgical problems and outcome related to the neonatal period. Thirty-six patients with the Robin sequence presenting from 1972 through 1990 were reviewed. A majority of patients had feeding and respiratory difficulties, to varying degrees, following birth. These problems were treated successfully by maneuvers ranging from positioning to two infants who eventually required tracheostomy. Thirty-four patients had palate repair. Age at repair averaged 16.2 months, and one third of patients had associated anomalies. Infants who experienced problems following palatoplasty were those who had histories of severe difficulties and complications in the early months of life. In addition, patients with associated congenital anomalies has significantly more problems at the time of palate repair than those without anomalies. Those patients with the Robin sequence, who historically had minimal difficulty following birth, experienced few complications at the time of palate repair. Of the 34 patients with repaired palates, 23 demonstrated sufficient follow-up to allow for evaluation of speech outcome. Satisfactory or normal speech production was noted in 65.4%. This is not significantly different from that observed in all patients undergoing cleft palate repair during this same time period (74.9%). Secondary pharyngoplasty procedures were required in 17.4%.(ABSTRACT TRUNCATED AT 250 WORDS)

Voice onset time in young and 70-year-old women.

This study was conducted to determine the effect of aging on voice onset time (VOT). Ten women between 20 and 30 years old and 10 women between 70 and 80 years old read CVC syllables embedded in a carrier phrase. Spectrograms were used to measure VOT for voiced and voiceless bilabial and velar stops in the context of high and low vowels. Findings revealed that VOT was generally the same in older and younger subjects, and both age groups maintained similar voiced/voiceless and bilabial/velar distinctions. Older subjects demonstrated significantly shorter VOTs only in certain contexts involving place of consonant production and vowel context. The effects of aging on VOT, therefore, seem to appear only in selected phonetic contexts.

Comparison of Nasometer and listener judgments of nasality in the assessment of velopharyngeal function after pharyngeal flap surgery.

This study examined the relationship between nasalance scores as derived from the Model 6200 Nasometer and listener judgments of perceived nasality for individuals with pharyngeal flaps. Sixteen individuals with pharyngeal flaps read a speech sample consisting of seven sentences for which associated nasalance scores were obtained. In addition, 10 trained listeners were asked to judge the subjects' audiorecorded speech samples for the degree of both hypernasality and hyponasality using two 6-point scales. The mean judges' ratings of hypernasality did not increase systematically with increasing nasalance scores or with decreasing hyponasality ratings. However, as the nasalance scores associated with nasal loaded sentences increased, a systematic decrease in listener perception of hyponasality occurred.

Apparent double defect in C11 beta and C21-steroid hydroxylation in congenital adrenal hyperplasia.

Some patients with either fully developed, mild or even hidden forms of congenital adrenal hyperplasia have both 21-deoxycortisol and increased 11-deoxycortisol in their blood and excrete "pregnanetriolone" and "tetrahydro-S" in their urine. The simultaneous presence of these compounds suggests two enzymic deficiencies, which are expressed in C21- and C11 beta-hydroxylases, respectively. However, these deficiencies have been inferred to derive from a single aberration in C11 beta-hydroxylase, whereby the enzyme acquires an affinity towards 21-deoxy precursors (i.e. 17-OH-progesterone) of cortisol and diminishes its activity against its regular 21-hydroxy intermediate 11-deoxycortisol. Depending on the severity of the aberration varying amounts of 21-deoxycortisol (expressing the aberrant 11 beta-hydroxylase) and of 11-deoxycortisol (expressing the normal 11 beta-hydroxylase) will be formed. An apparent two-level inhibition of cortisol biosynthesis will result from: (1) the low activity of normal 21-hydroxylase on the derivative 21-deoxycortisol, produced by the action of the aberrant 11 beta-hydroxylase, and (2) the low supply of 11-deoxycortisol for the regular but decreased (due to the aberration) 11 beta-hydroxylase. Thus a single defect will mimic at one and the same time a 21-hydroxylase and a 11 beta-hydroxylase deficiency.