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Biomedical subjects

E Y Yang

Publications and source records attributed to E Y Yang.

At least 37 records · Page 2Linked to original sources
PubMed1998

Fetoscopy.

Fetoscopy involves the application of microlaparoscopic technology to fetal diagnosis and therapeutic intervention. Though fetoscopy presents many potential advantages over open fetal surgery, the primary one is that of decreased procedure-induced preterm labor and fetal loss from preterm delivery. The small uterine puncture sites required for fetoscopic surgery should, in theory, obviate the morbidity of a large hysterotomy. Fetoscopic instrumentation is small by design, but this has not limited the breadth of the interventional spectrum, because creative applications have been used for the treatment of twin-twin transfusion syndrome, twin reversed arterial perfusion sequence, hydronephrosis, congenital diaphragmatic hernia, fetal tumors, and myelomeningocele. This article examines the fetoscopic experience for these applications, involving over 150 cases. The results for many procedures are auspicious and will improve as further operative experience and newer fetoscopic technologies become available. However, as with any novel technology, responsible application must involve careful experimentation and an analysis of potential maternal and fetal benefits.

Animals↗
PubMed1997

Fetoscopic gene therapy for congenital lung disease.

Fetal gene therapy offers the promise of cure for certain genetic diseases, like cystic fibrosis and surfactant protein B deficiency. The authors hypothesized that a fetoscopic approach could attain a high level of organ-specific gene transfer to the fetal lung late in gestation. To test this hypothesis the authors examined the efficacy, specificity, and toxicity of recombinant adenovirus-mediated transfer of the beta-galactosidase marker gene to the lung of late gestation fetal sheep using a fetoscopic technique. Twelve fetal sheep of 125 to 135 days' gestation (term, 145 days) underwent fetoscopic bronchoscopy and intratracheal administration of a replication-deficient adenoviral vector that transduces the beta-galactosidase marker gene. Escape of administered virus was prevented by the fetoscopic deployment of a detachable silicone balloon in the fetal trachea. All fetuses survived until being killed at 2 days after vector delivery for the histopathologic assessment of vector efficacy and specificity. Optimal beta-galactosidase transgene expression was observed at a viral titer of 2 x 10(12) particles per milliliter of administered volume. Expression was greatest in the distal pulmonary parenchyma, particularly in type II pneumocytes, and extended out to the pleura. There was no evidence of gene transfer in either the large conducting airways or in any other fetal organ. The authors have developed a minimally invasive technique for the specific pulmonary delivery of gene therapy vectors to the fetus with no associated acute toxicity. Gene transfer to the late gestation fetus for the treatment of congenital pulmonary disease may be feasible through fetoscopy.

Adenoviruses, Human↗
PubMed1997

Myofibroblast persistence in fetal sheep wounds is associated with scar formation.

The scarless repair capabilities of the fetus are influenced by the size of the wound and the gestational age of the fetus. Whereas small wounds heal scarlessly, large wounds in the same fetus heal with scar. Myofibroblasts are specialized fibroblasts that express alpha-smooth muscle actin (alpha-SMA), a contractile cytoskeletal protein. The authors hypothesized that small fetal wounds that heal scarlessly will have a relative absence of myofibroblasts, whereas large wounds that heal with scar will have abundant myofibroblasts. In this study, an incisional wound and four punch biopsy wounds of 2, 4, 6, and 10 mm diameter were placed on the backs of 60- to 90-day-gestation fetal sheep (term, 145 days). Fourteen days after wounding, the healed fetal wounds were harvested, the repair morphology was determined (scarless, transitional repair, or scar), and the expression of alpha-SMA was analyzed by immunohistochemistry. In the second part of this study the authors analyzed the temporal expression of alpha-SMA in fetal wounds at 1, 2, 3, and 7 days after wounding in 70-day-gestation fetal sheep. In the 14-day wounds, the authors found that alpha-SMA was not expressed in any incisional or 2-mm wound that healed scarlessly, but it was expressed in all wounds that healed with scar. Overall, alpha-SMA expression strongly correlated with increasing wound size (P < .005). Myofibroblasts were seen as early as 24 hours after wounding, and at 3 and 7 days all wounds showed strong expression of alpha-SMA. These results demonstrate that although myofibroblasts are induced early in fetal wound repair, by 14 days there is a notable lack of myofibroblasts in wounds that heal scarlessly and an abundance of myofibroblasts in those wounds that scar. By determining the factors that regulate the disappearance of the myofibroblast in scarless fetal wounds, the authors hope to gain new insights into the mechanisms of scarless fetal repair.

Actins↗
PubMed1997

Wound size and gestational age modulate scar formation in fetal wound repair.

The early-gestation fetus heals incisional skin wounds rapidly and scarlessly. The morphology with which the fetus heals excisional skin wounds remains unclear. To characterize excisional fetal wound repair, and to determine whether there is a developmentally regulated wound-size threshold beyond which fetal skin heals with scar, the authors created excisional wounds in fetal lambs of varying gestational age. Time-mated pregnant ewes carrying 22 fetuses at 60 to 90 days' gestation (term, 145 days) underwent laparotomy and hysterotomy. An incisional wound and four circular, punch biopsy wounds of 2, 4, 6, and 10 mm in diameter were placed on the back of each fetal lamb and marked with India ink. The wounds were harvested at 14 days' postwounding and examined grossly and microscopically after serial sectioning and histological staining. Morphological features of all wounds were graded. By 14 days' postwounding all fetal wounds had healed completely. for lambs at each gestational age, increasing wound size was strongly associated with an increase in the frequency of scar. Also, as gestational age increased from 60 to 90 days' gestation the frequency of scarless repair decreased. By understanding the cellular and molecular processes that mediate scar formation with increasing wound size and advancing gestational age, the authors hope to gain further insight into the mechanisms of scarless fetal wound repair.

Animals↗
PubMed1996

Infant hearing screening with an automated auditory brainstem response screener and the auditory brainstem response.

From 1653 babies hospitalized in the Veterans General Hospital-Taipei from 1993 to 1995, 260 infants at risk of hearing impairment were selected. The risk criteria of hearing impairment for neonates were based on the recommendation of the US Joint Committee on Infant Hearing, 1990 Position Statement. All these infants were screened with the Algo-1 Plus, an automated auditory brainstem response (ABR) screener at a mean postconceptional age of 40.7 +/- 4.5 weeks. Thirty-nine cases (39/260, 15%) involving 57 ears (57/520, 11%), failed the screening. Except for one infant who died, the babies had an ABR test for both air- and bone-conducted stimuli and an otological examination. The case-specific incidence of conductive hearing deficit at the initial ABR test was 5.4%. The prevalence of sensorineural hearing deficits was between 2.3% confirmed and 3.1% including infants who did not have follow-up tests. The kappa-value that indicated agreement between the Algo-1 and ABR results was 0.64, and the overall efficiency of using Algo-1 to correctly identify pass or failure of the ABR was 83%.

Audiometry, Evoked Response↗
PubMed1996

Salivary binding antibodies induced by human immunodeficiency virus type 1 recombinant gp120 vaccine. The NIAID AIDS Vaccine Evaluation Group.

Salivary binding antibodies induced by candidate human immunodeficiency virus type 1 (HIV-1) vaccines in healthy, HIV-1 uninfected volunteers were assessed in a clinical trial evaluating intramuscularly injected HIV-1MN recombinant gp120 (rgp120) vaccine alone or with HIV-1IIIB rgp120 vaccine. The two rgp120 vaccines induced envelope glycoprotein-specific immunoglobulin G (IgG) and IgA antibodies in whole saliva and serum.

AIDS Vaccines↗
PubMed1995

Cystic neoplasms of the pancreas. A clinicopathologic study, including DNA flow cytometry.

OBJECTIVE: To review the classification, clinical behavior, and appropriate therapy for cystic neoplasms of the pancreas. We examined patient demographics, clinical parameters, preoperative imaging modalities, histologic findings, and tumor DNA content to determine which best predict outcome. DESIGN: Case series and survey of pathologic specimens. SETTING: Tertiary care center. PATIENTS: Twenty-two patients with cystic neoplasms of the pancreas treated at affiliates of Northwestern University Medical School, Chicago, Ill. MAIN OUTCOME MEASURES: Predictive value of preoperative testing, tumor DNA content, patient survival. RESULTS: In 20 patients undergoing computed tomographic scan, the tumor was visualized in every case. All other imaging studies evaluated were less likely to demonstrate the lesion. Eight of 10 patients with serous cystadenomas were alive with no evidence of disease at the time of this report; one patient was alive with local recurrence, and a second patient had died of unrelated causes. All patients with mucinous cystadenomas were alive with no evidence of disease. Three of seven patients with cystadenocarcinomas had aneuploid, high S-phase tumors, and one had a diploid, high S-phase tumor; all four died (mean survival, 4.8 months). Two patients with cystadenocarcinomas had diploid, low S-phase tumors; both were long-term survivors but died of their disease at 8.6 and 9.3 years. CONCLUSIONS: (1) Computed tomographic scan is the most valuable diagnostic imaging study for preoperative evaluation of these patients. (2) Precise preoperative determination of tumor type is not possible. (3) DNA flow cytometry may help identify patients with aggressive tumors who may benefit from adjuvant chemoradiation.

Actuarial Analysis↗
PubMed1994

Effect of high-pass filtering on the neonatal auditory brainstem response to air- and bone-conducted clicks.

The effect of standard high-pass analog filtering on the neonatal auditory brainstem response (ABR) to air- and bone-conducted clicks at low intensity screening levels was investigated. Simultaneous three channel recorded ABRs were obtained from 20 neonates with filter settings of 30-3000, 100-3000, and 150-3000 Hz at intensity levels of 20, 30, and 40 dB nHL. Statistically significant reductions in wave V amplitude and decreases in wave V latency were observed for both transducers across all three low level stimulus intensities with the progressive increase in the high-pass filter cutoff (p < .05). These data support the advocacy of less restrictive high-pass filtering (e.g., 30 Hz) for neonatal and infant ABR screening to air- and bone-conducted clicks.

Adult↗
PubMed1994

Neonatal auditory brainstem response thresholds to air- and bone-conducted clicks: 0 to 96 hours postpartum.

Auditory brainstem response (ABR) thresholds to air- and bone-conducted clicks were investigated in 40 full-term neonates. Subjects were divided into two groups of 20 according to postpartum age: less than 48 hours and between 49 and 96 hours. Mean ABR thresholds to air- and bone-conducted clicks for neonates less than 48 hours postpartum were 14.5 dB nHL (51.5 dB peak SPL) and 1.8 dB nHL (36.8 peak re: 1 microN), respectively, while those for neonates between 49 and 96 hours were 3.8 dB nHL (40.8 dB peak SPL) and 1.5 dB nHL (36.5 dB peak re: 1 microN), respectively. A significant difference was found between the two group mean ABR thresholds to air-conducted stimuli (p < .0001) but not for the bone-conducted stimuli (p < .8959). A statistically significant within-group difference was found between the ABR thresholds to air- and bone-conducted stimuli for only the neonates less than 48 hours of age (p < .0001). When the data was collapsed across groups, simple linear regression analyses revealed a statistically significant relation between postpartum age and ABR threshold to air-conducted stimuli (p < .0001) and a nonsignificant relation between postpartum age and ABR threshold to bone-conducted stimuli (p < .9744). These findings support the notion that some resolution of fluids and residuals in the middle ear occurs during the first 48 hours postpartum and that air-conducted stimuli are attenuated during that period. As such, a physiologic conductive deficit among the younger neonates is suggested.

Acoustic Stimulation↗
PubMed1993

Auditory brain stem responses to air- and bone-conducted clicks in the audiological assessment of at-risk infants.

Auditory brain stem responses (ABRs) to air- and bone-conducted clicks were used to assess the auditory status of 170 at-risk neonates. During the perinatal period, 20.6% (35/170 cases) of the at-risk infants failed ABRs to air-conducted clicks at 30 dB nHL in at least one ear. Ear-specific results indicated an initial failure rate of 15.0% (51/340 ears). Approximately two-thirds (32/51 ears) of these initial failures showed purely conductive deficits, whereas the remaining one-third (19/51 ears) involved suspected sensorineural components. Follow-up audiological evaluations were performed for 87.1% (148 cases) of these at-risk infants at 4 mo and/or 1 yr corrected age. Based on the initial tests and follow-up assessments, the tentative operating characteristics of ABRs to both air- and bone-conducted clicks for identification of sensorineural deficits in at-risk neonates were calculated. It was found that the ABR to bone-conducted clicks yielded better specificity, predictive value of positive results, and overall efficiency. It is suggested that the ABR to bone-conducted stimuli should be viewed as a valuable addition in the assessment of cochlear reserve in infants who fail a newborn auditory screening to air-conducted stimuli.

Acoustic Stimulation↗
PubMed1993

Test-retest variability of the auditory brainstem response to bone-conducted clicks in newborn infants.

The variability of the auditory brainstem response (ABR) to bone- and air-conducted clicks was investigated utilizing a test-retest paradigm with 20 normal full-term newborn infants. ABRs to bone-conducted clicks at 15 and 30 dB nHL and air-conducted clicks at 30 dB nHL were obtained. The delivery of the bone-conducted signal was controlled. ABR wave V latencies were measured from each test-retest stimulus condition. The results indicated no statistically significant difference in test-retest variability of ABR wave V latencies or amplitudes between bone- and air-conducted clicks. ABRs to bone-conducted clicks, under controlled clinical conditions, are as reproducible and reliable as ABRs to air-conducted clicks in newborn infants.

Acoustic Stimulation↗
PubMed1993

Tyrosine inhibits intestinal-phase gastric-acid secretion.

BACKGROUND: Intestinal infusion of leucine augments the maximal gastric-acid secretory response to pentagastrin and serves as a bioassay for intestinal-phase acid secretion. Another action of leucine is to decrease tyrosine flux into neural tissues. We hypothesized that the mechanism of leucine-stimulated acid secretion involves its ability to alter tyrosine absorption. METHODS: We administered tyrosine intrajejunally and intravenously to anesthetized, vagotomized rats during maximal pentagastrin stimulation and measured acid output in response to intrajejunal infusion of leucine. RESULTS: Intrajejunal tyrosine produced a dose-dependent inhibition of leucine-stimulated acid secretion but only mild effects on acid secretion in response to pentagastrin alone. Intravenous tyrosine infusions also decreased acid secretion in response to intestinal leucine but required much higher doses. CONCLUSIONS: Tyrosine exerts a specific inhibitory effect on leucine-stimulated acid secretion, which is mediated intraluminally. Because tyrosine is an important regulator of adrenergic nervous system activity, we speculate that the mechanism of leucine-stimulated acid secretion may involve modulation of the sympathetic nervous system, thereby affecting acid secretion.

Animals↗
PubMed1993

Auditory brainstem response thresholds to air and bone conducted clicks in neonates and adults.

Auditory brainstem response (ABR) thresholds to air and bone conducted clicks were investigated in 20 full-term neonates and 20 normal-hearing young adults. Results showed mean ABR thresholds to air and bone conducted clicks for neonates to be 3.75 dB nHL (40.75 peak SPL) and 1.25 dB nHL (36.25 dB peak re: 1 microN), respectively, and for adults 3.75 dB nHL (40.75 peak SPL) and 18.75 dB nHL (53.75 peak re: 1 microN), respectively. A significant difference was observed in mean ABR thresholds to bone conducted stimuli between neonates and adults (p < 0.0001) and among mean adult ABR thresholds to air and bone conducted stimuli (p < 0.0001). Nonsignificant differences were observed in mean ABR thresholds to air and bone conducted stimuli among neonates (p > 0.05) and in mean ABR thresholds to air conducted stimuli between neonates and adults (p = 1.00). It is speculated that the dissimilarity in the relationship of thresholds to air and bone conducted stimuli between neonates and adults reflects, in part, a difference in efficiency of signal delivery to the cochlea.

Acoustic Stimulation↗
PubMed1991

Regulation of epithelial proliferation by TGF-beta.

The closely related mammalian TGF-betas (TGF-beta 1, TGF-beta 2 and TGF-beta 3) are potent inhibitors of proliferation of many cell types in vitro. TGF-beta 1 has been demonstrated to be growth inhibitory in vivo for epithelial, endothelial, myeloid and lymphoid cells. Utilizing skin keratinocytes as a model system for studying the mechanism of TGF-beta 1-induced growth inhibition, it has been demonstrated that TGF-beta 1 rapidly inhibits transcription of the c-myc gene. Antisense c-myc oligonucleotides inhibit proliferation of keratinocytes as effectively as does TGF-beta 1, indicating that TGF-beta 1 suppression of c-myc expression is an important component of this growth inhibition. Studies utilizing DNA tumour virus transforming gene constructs have shown that the retinoblastoma gene product, pRb, or a related protein, is needed for TGF-beta 1 suppression of c-myc transcription. Thus, TGF-beta 1 may act through a tumour suppressor gene product, pRb, to suppress transcription of a proto-oncogene, c-myc, and subsequently inhibit cell proliferation.

Animals↗
PubMed1991

Effect of vibrator to head coupling force on the auditory brain stem response to bone conducted clicks in newborn infants.

The effect of vibrator to head coupling force on the auditory brain stem response (ABR) to bone conducted clicks in newborn infants was investigated. Twenty full term newborn infants were tested. ABRs to bone conducted clicks were obtained with four different coupling forces (225, 325, 425, and 525 g) at stimulus intensities of 15 and 30 dB nHL. ABRs to air conducted clicks were also obtained at 30 dB nHL. The results of this study indicated that ABR wave V latencies to bone conducted clicks in newborn infants were affected significantly when the vibrator to head coupling force shift exceeded 200 g. It is recommended that the coupling force be controlled and remain consistent when implementing ABR to bone conducted stimuli in newborn infants.

Audiometry, Evoked Response↗
PubMed1991

TGF beta regulation of epithelial cell proliferation: role of tumor suppressor genes.

Transforming growth factor beta 1 (TGF beta 1) is the prototype of a large family of polypeptides involved in growth control, extracellular matrix production, and development. The TGF beta s have marked stimulatory effects on connective tissue formation. They are chemotactic for fibroblasts, indirect mitogens for certain mesenchymal cells and stimulators of extracellular matrix deposition. The TGF beta s are also potent inhibitors of proliferation of most cell types in culture, and in vivo studies have indicated that the predominant effect of TGF beta 1 on cell proliferation is inhibition. We have investigated the mechanism of TGF beta 1 inhibition of skin keratinocyte growth. Earlier studies demonstrated that TGF beta 1 inhibition of keratinocyte proliferation involves suppression of c-myc transcription, and indirect evidence suggested that the product of the retinoblastoma tumor susceptibility gene, pRB, may be involved in this process. More recently, we have shown that transient expression of pRB in skin keratinocytes can repress human c-myc promoter/CAT transcription as effectively as TGF beta 1. The same c-myc promoter region, termed the TGF beta control element (TCE), was required for regulation by both TGF beta 1 and pRB. Oligonucleotides containing the TCE bound to several nuclear factors in mobility shift assays and a cellular protein of approximately 106 kD in Southwestern assays. Binding of these factors could be demonstrated in cells with or without normal pRB, and the binding of some factors was rapidly inhibited by TGF beta 1 treatment of TGF beta-sensitive but not TGF beta-insensitive cells. These data indicate that pRB can function to inhibit c-myc transcription and suggest the involvement of cellular factor(s) in addition to pRB in the TGF beta 1 pathway for suppression of c-myc transcription. Studies with other cell types have shown that another tumor suppressor gene, p53, can also regulate transcription of c-myc in transient assays. Whereas wild type p53 markedly suppressed transcription, four different mutant p53 clones caused transactivation. The data support the hypothesis that pRB and p53 can both cause growth inhibition by blocking the expression of the protooncogene, c-myc, and indicate that tumor suppressor genes may function in the response pathway for diffusible negative growth regulators such as TGF beta.

Animals↗