TGF-beta stimulation and inhibition of cell proliferation: new mechanistic insights.
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Animals↗
Biomedical subjects
E Y Yang
Publications and source records attributed to E Y Yang.
Transforming growth factor beta 1-induced changes in cell migration, proliferation, and angiogenesis in the chicken chorioallantoic membrane.
Application of TGF beta 1 (10-100 ng) to the chicken chorioallantoic membrane (CAM) for 72 h resulted in a dose-dependent, gross angiogenic response. The vascular effects induced by TGF beta 1 were qualitatively different than those induced by maximal doses of basic FGF (bFGF) (500 ng). While TGF beta 1 induced the formation of large blood vessels by 72 h, bFGF induced primarily small blood vessels. Histologic analysis revealed that TGF beta 1 stimulated pleiotropic cellular responses in the CAM. Increases in fibroblast and epithelial cell density in the area of TGF beta 1 delivery were observed as early as 4 h after TGF beta 1 treatment. By 8 h, these cell types also demonstrated altered morphology and marked inhibition of proliferation as evidenced by 3H-thymidine labeling. Thus, the TGF beta 1-stimulated accumulation of these cell types was the result of cellular chemotaxis from peripheral areas into the area of TGF beta 1 delivery. Microscopic angiogenesis in the form of capillary sprouts and increased endothelial cell density first became evident at 16 h. By 24 h, capillary cords appeared within the mesenchyme of the CAM, extending towards the point of TGF beta 1 delivery. 3H-thymidine labeling revealed that the growth of these capillary cords was due to endothelial cell proliferation. Finally, perivascular mononuclear inflammation did not become evident until 48 h of treatment, and its presence correlated spatially and temporally with the gross and histological remodelling of newly formed capillary cords into larger blood vessels. In summary, these data suggest that, in the chicken CAM, TGF beta 1 initiates a sequence of cellular responses that results in growth inhibition, cellular accumulation through migration, and microvascular angiogenesis.
Allantois↗
Effect of temporal area bone vibrator placement on auditory brain stem response in newborn infants.
The effect of bone conduction vibratory placement on the temporal area, revealed by the auditory brain stem response (ABR), in newborn infants, was investigated. Twenty-five full term neonates were tested at 48 to 72 hours postparturition. ABR wave V latencies were obtained from three different temporal area postauricular vibrator placements at 15 and 30 dB nHL stimulus intensity levels. Results showed that significant ABR wave V latency shifts were observed with changes in the three vibrator placements (p less than 0.05). It is suggested that, with ABR testing in newborn infants using bone conducted stimuli, bone vibrator placement on the temporal area remain consistent.
Audiometry, Evoked Response↗
Expression of and response to growth regulatory peptides by two human pancreatic carcinoma cell lines.
Two human pancreatic adenocarcinoma cell lines (PANC 1 and MIA PACA 2) were examined for expression of growth factors that could potentially play a role either in growth regulation of the tumor cells, or in cells that comprise the stromal elements of tumors. Both cell lines expressed transforming growth factor-alpha (TGF alpha), basic fibroblast growth factor (bFGF), c-sis (PDGF B chain), TGF beta 1, and TGF beta 3 mRNA by Northern blot analysis. Only the PANC 1 cells, however, expressed the TGF beta 2 transcript. TGF beta-like competing activity was found in medium conditioned by either cell line, but TGF alpha-like [epidermal growth factor (EGF)-competing] activity was not detected in the medium from either cell line by radioreceptor assay. TGF alpha and EGF caused concentration-dependent stimulation of soft agar colony growth of the MIA PACA 2 cells, while only TGF alpha caused a significant but less dramatic stimulation of soft agar growth of the PANC 1 cells. Insulin stimulated the anchorage-independent growth of MIA PACA 2 but not PANC 1 cells. Likewise, bFGF also caused a concentration-dependent stimulation of MIA PACA 2 but not PANC 1 growth in soft agar, and PDGF had no effect on the growth of either cell line. TGF beta had no inhibitory or stimulatory effect on soft agar colony growth of either the PANC 1 or the MIA PACA 2 cells, although both cell lines exhibited high affinity, saturable TGF beta binding sites, and TGF beta 1 was capable of autoinduction of TGF beta 1 mRNA expression in PANC 1 cells. The ability to continue to respond to positive growth regulatory factors coupled with the loss of responsiveness to negative growth factors may be important in the pathogenicity of these aggressive tumors.
Adenocarcinoma↗
A developmental study of bone conduction auditory brain stem response in infants.
Two studies, vibrator placement and masking, were performed to evaluate the developmental aspect of bone conduction auditory brain stem response (ABR) in human infants. Subject groups included newborns, 1-yr-olds, and adults. In the vibrator studies, ABRs were obtained from placements of the bone conduction vibrator on the frontal, occipital, and temporal bones. Results showed that temporal placements in neonates and 1-yr-olds produce significantly shorter wave V latencies of ABR than frontal or occipital placements. In adults, differences of wave V latencies from various vibrator placements were comparatively small. In the masking studies, ABRs were acquired from vibrator placements at the temporal bone in the presence of ipsilateral air conducted masking noise from the experimental groups. Results showed that interaural attenuations of bone conduction click stimuli are the largest in neonates, somewhat smaller from 1-yr-olds, and the smallest in adults. The findings of this research strongly suggest that temporal placements for bone conduction ABR should be used, in some instances, when testing infants and 1-yr-olds. The results of this study support the proposition that bone conduction ABR is a feasible and reliable diagnostic tool in testing infants.
Adult↗
Neonatal auditory brainstem responses recorded from four electrode montages.
Simultaneous auditory brainstem responses (ABRs) to click stimuli at 30 and 60 dB nHL were recorded from 16 full term neonates with four electrode arrays: vertical (Cz-Nape of neck), ipsilateral (Cz-Mi), contralateral (Cz-Mc), and horizontal (Mc-Mi). Results indicated that ABR waveforms were morphologically similar to those recorded in adults: Waves I, III, and V were clearly identifiable and of the same polarity in 15 of 16 subjects 60 dB nHL and Wave V was clearly identifiable in 14 of 16 subjects at 30 dB nHL. Although ABR waves were identified in most cases, waveforms expression was variable with different electrode recording montages. It is suggested that if a clinician must choose one montage array for recording neonatal ABRs at high intensity levels for neurodiagnostic evaluations, the ipsilateral recording array is indicated since it displays the highest expression of wave components. For screening applications or threshold searching at lower stimulus levels, however, either the ipsilateral or vertical montage would be justified. Further, caution should be employed when interpreting ABR results in neonates recorded with unconventional montages due to the variable expression of wave components.
Electrodes↗
Gender effects in auditory brainstem responses to air- and bone-conducted clicks in neonates.
UNLABELLED: Examinations of gender differences in auditory brainstem response (ABR) wave V latencies and thresholds to air- and bone-conducted clicks were undertaken with neonates. Two hundred and two full-term neonates participated (i.e., 103 males and 99 females). Wave V latency measures for air- and bone-conducted click stimuli of 30, 45, and 60 dB nHL and 15 and 30 dB nHL, respectively, and thresholds to air- and bone-conducted clicks were determined. Female newborns displayed statistically significant shorter wave V latencies than male newborns for air-conducted click stimuli (i.e., approximately 0.2-0.3 ms; P=.0016). There were no significant gender differences in wave V latencies to bone-conducted click stimuli (P=.11). With respect to ABR thresholds, no statistically significant differences were observed for either air-conducted clicks (P=.054) or bone-conducted clicks (P=.18). EDUCATIONAL OBJECTIVES: As a result of this activity, the participant will be able to (1) describe gender differences in ABR wave V latencies and thresholds to air- and bone-conducted clicks with neonates and (2) summarize possible explanations for observed gender differences in ABR wave V latencies and thresholds to air- and bone-conducted clicks with neonates.
Auditory Threshold↗