The distribution of FGF-2 and TGF-beta within the lacrimal gland of rabbits.
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Biomedical subjects
Publications and source records attributed to D W Warren.
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Co-culturing autologous lacrimal gland cells and immune system cells can lead to spleen cell proliferation with a time course similar to that for proliferation in a typical heterologous MLR. Although these results are consistent with the hypothesis that lacrimal acinar cells are a source of antigen, and may or may not serve in part as an APC, future studies of this preparation are required to test these hypotheses. We are unaware of reports demonstrating that co-culturing control epithelial tissue and autologous splenic lymphocytes from apparently healthy animals leads to lymphocytic proliferation. Our results suggest that the appropriate co-culture of tissues and immune cells from healthy animals, perhaps such as detailed above, should help identify mechanisms contributing to the induction of autoimmune disease. Knowledge regarding such mechanisms should help efforts to prevent such disease, and perhaps reverse it.
OBJECTIVE: The objective of this study was to determine the influence of velopharyngeal (VP) inadequacy on respiratory speech compensations. DESIGN: The pressure-flow technique was used to measure pressure, airflow, and timing variables associated with VP closure during the production of the initial plosive consonant /p/ in a series of the utterance "papa." SETTING: The study was conducted in the speech and breathing laboratory of the UNC Craniofacial Center. PARTICIPANTS: Eighty-two subjects with cleft lip and/or palate were assessed. The subjects were divided into two groups, those with adequate VP closure (VP size <.010 cm2) and those with inadequate VP closure (VP size >0.10 cm2). The adequate group was comprised of 62 subjects, and 20 subjects were categorized as inadequate. RESULTS: Peak intraoral pressure decreased in the inadequate group, but the difference was not significant. Nasal airflow increased (p < .01), but duration of the pressure pulse was the same for both groups. The area under the pressure curve decreased for the inadequate group (p = .04). CONCLUSION: These data contrast with previously reported published data using /p/ in the utterance "hamper." This suggests that phonetic context influences the compensatory response to velopharyngeal inadequacy. Additionally, while the findings are somewhat similar to studies that involved noncleft subjects whose oral airway was suddenly vented during the production of /p/, there is enough difference to suggest that learning also affects the compensatory outcome.
OBJECTIVE:To evaluated of speech aid's function with air flow pressure techniques. METHODS: The study group contained 12 patients with cleft palate,submucous cleft palate and congenital velopharyngeal insufficiency who had been found to have VPI(velopharyngeal insufficiciency) and hypernasal speech and were scheduled for speech aid. RESULTS: It was confirmed that study was to assess the relationship between oral-nasal resonance with and without the speech aid. CONCLUSION: The speech aid be able to improve the velopharyngeal function in some VPI patients,also it is useful clinical results for the speech therapiist.
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The effects of dihydrotestosterone (DHT) (1 mg/kg) on biochemical parameters related to lacrimal secretion, basal tear flow rate, and pilocarpine-stimulated lacrimal gland fluid secretion, in mature ovariectomized rabbits were studied. The effects of the synthetic estrogen diethylstilbestrol (DES) (100 micrograms/kg), on lacrimal gland biochemical parameters in normal mature female rabbits was also studied. Ovariectomy decreased the total serum levels of testosterone (T) by 88.5% and androstenedione by 35.9%, without changing the levels of dehydroepiandrosterone (DHEA) of its sulfate. Ovariectomy caused a significant regression of the lacrimal glands, decreasing total DNA by 35%, and total protein by 22%. DHT treatment of ovariectomized animals prevented lacrimal gland regression, increasing total gland DNA (31%) and total protein (18%). DHT treatment also increases Na+, K(+)-ATPase activity (29%) and beta-adrenergic receptor binding sites (23%) compared to the ovariectomized group. DHT increased pilocarpine stimulated lacrimal gland fluid secretion (13.26 +/- 1.47 microL/min) compared to the ovariectomized group (7.72 +/- 0.41 microL/min), but DHT treatment paradoxically decreased basal tear flow rate (1.02 +/- 0.04 microL/min) as compared to the ovariectomized rabbits (1.96 +/- 0.12 microL/min). DES decreased the total serum T from 59.33 +/- 10.54 pg/mL to 21.5 +/- 6.06 pg/mL. DES decreased total Na+,K(+)-ATPase by 12% and increased beta-adrenergic receptor binding sites by 83.3%. These results suggest that androgens play a major role in supporting lacrimal gland secretory function. Additionally, they suggest that estrogens may influence certain aspects of lacrimal functions, although it is not clear to what extent those actions are elicited directly or indirectly.
The speech respiratory system is configured in ways that tend to maximize its ability to respond to changes in the airway environment. Intraoral pressures remain at levels sufficient to generate reliably recognized consonant sounds even in the presence of structural deficits such as velopharyngeal inadequacy. Similar respiratory compensations occur when bite blocks and bleed valves are used to vent airway pressures. The purpose of the present study was to determine the sensitivity of the monitoring system psychophysically and to assess its physiological response to sudden, unanticipated perturbations. Twenty adults were asked to produce the utterance/pa/, and a calibrated perturbator valve permitted air to escape from the oral cavity on randomly selected productions. Respiratory responses were recorded using PERCI-SARS instrumentation. The results indicated that sudden openings of 0.14 cm2 (SD = 0.04) were detected by speakers. Compensatory respiratory responses to suprathreshold pressure-venting occurred rapidly (i.e., 27 ms [SD = 8]) after valve opening. Although peak pressure and area under the pressure pulse fell with valve opening, the magnitude of pressure was nevertheless sufficient for sound generation. Measurements of the slope of the rise in intraoral pressure after subthreshold pressure-venting in 10 participants were compared to measurements obtained from an-elastic model of the upper airway. The data demonstrated a significant difference between vented and unvented conditions for the model, but not the participants. This suggests that elastic recoil is actively and unconsciously controlled in humans to compensate for losses in airway pressure during speech.
The expression of LH receptor (LHR) mRNA was studied in fetal rat gonads using polymerase chain reaction multiplication of reverse-transcribed mRNA. A primer pair corresponding to the extracellular domain of the receptor revealed the expression of LHR mRNA in fetal ovaries and testes as early as embryonic Day 13.5, the earliest age studied. The localization of LHR mRNA was examined in the perinatal rat ovary using in situ hybridization with two antisense probes, one encoding the extracellular and the other encoding the transmembrane domains of LHR. At the age of 4 days, only the extracellular LHR probe gave specific signal over ovarian stromal and follicular cells, excluding the ova. Three days later, similar distribution of specific hybridization was observed with both probes. In the 10- and 30-day-old rat ovaries, clear expression of LHR mRNA was found to be with both probes in theca cells. Gonadotropin-stimulated production of cAMP was studied in cultures of dispersed perinatal rat ovarian cells. When 5-day-old ovarian cells were cultured for 3 days in vitro and then stimulated by either hCG (0.1 mg/L) or FSH (1 mg/L) for 6 h, cAMP production was enhanced only in cells stimulated by FSH. In a similar experiment with 7-day-old ovarian cells, cAMP production was stimulated by both FSH and hCG. Stimulation with hCG (0.1 mg/L) during the 3-day culture caused homologous desensitization of cAMP production, but stimulation with FSH (0.1 mg/L) had no such effect. The desensitization of the LHR was also investigated by treating neonatal rats in vivo with a high dose of hCG (600 IU/kg BW s.c. as a single injection on Day 7) or with a dosage of recombinant human (rec) FSH on Days 3-9 (0.3 IU s.c twice daily). Thereafter, at the age of 10 days, the ovaries were incubated either with recFSH (200 IU/L) or hCG (CR-121; 0.1 mg/L) for 1 h. Homologous desensitization of cAMP production by hCG was observed, but the FSH-mediated cAMP production was not affected. The hCG-induced steroidogenesis (progesterone and testosterone production) was not desensitized. In conclusion, these findings indicate that 1) the expression of the mRNA encoding the extracellular domain of LHR, i.e., truncated receptor, occurs in fetal rat gonads as early as embryonic Day 13.5; 2) the expression of the truncated LHR mRNA occurs uniformly in the differentiating ovarian cells before the appearance of the functional theca cell layer; 3) full-length LHR message appears in the developing ovary concomitantly with appearance of differentiated theca cells; 4) homologous desensitization of cAMP output by hCG, without steroidogenic desensitization, is present in perinatal rat ovaries; and 5) no FSH-evoked desensitization of cAMP production occurs in perinatal ovaries.
Nasometry and nasal cross-sectional area data were obtained from 80 normal male and female speakers (40 African-Americans and 40 white Americans) all of whom were over the age of 18 and spoke the Mid-Atlantic dialect of American English. The nasalance scores for readings of the Zoo Passage did not differ significantly between the groups. However, nasalance scores for readings of the Nasal Sentences were found to be significantly higher among the white speakers. The pressure-flow method was used to obtain nasal cross-sectional area values. There were no racial differences in nasal cross-sectional area. The Nasal Sentences scores were not highly correlated with nasal cross-sectional area. The clinical significance of these findings is discussed.
Nasal resistance (NRZ) values for healthy adults range from 1.0 to 3.5 cm H2O/L/sec. Some oral breathing tends to occur at values above 3.5. The purpose of the present study was to determine at what level of NRZ individuals sense that nasal breathing is difficult. A diaphragm was used to add four different resistance loads in random to 15 adult subjects. These loads were 5,8, and 15 cm H2O/L/sec and a value 40% above the individual's normal NRZ. Loads were added under four conditions: normal breathing, fixed flow rate, fixed breathing rate, and fixed flow and breathing rate. The pressure-flow technique was used to measure NRZ under all conditions. The study revealed that the sensation of breathing difficulty occurred at a median resistance of 5 cm H2O/L/sec and, as subjects were constrained to maintain fixed flow and breathing rates, the magnitude of RZ, at which the sensation of dyspnea was noted, decreased. The values observed in this study support previous findings suggesting that individuals switch to some oral breathing to maintain an adequate level of upper airway resistance at values between 3.5 and 4.5 cm H2O/L/sec. The findings also show that individuals attempt to minimize increases in airway resistance by modifying breathing behaviors.
PURPOSE: Endothelin-1 (ET-1) has been found to accelerate rabbit corneal epithelial wound healing in vivo and proliferation of rabbit and bovine epithelial cells in vitro. We have now determined that endothelin-like immunoreactivity (ET-LI) is present in the tear fluid of New Zealand white rabbits, and we have addressed the question of whether it is produced by the tear glands (lacrimal gland and Harderian gland). METHODS: Tears were obtained with capillary pipettes and lacrimal gland fluid was collected by cannulation. ET-LI was determined with a sandwich-enzyme immunoassay. The reverse transcriptase-polymerase chain reaction (RT-PCR) was employed to determine if there are gene transcripts for prepro ET-1 in tear glands. ET-LI in the tear glands was evaluated using immunohistochemistry. RESULTS: The tears contained 13.85 +/- 3.94 pg/ml (mean +/- SEM, n = 6) ET-LI and the lacrimal gland fluid had 24.90 +/- 6.00 pg/ml (n = 6). The plasma contained 0.89 +/- 0.20 pg/ml (n = 6). Gene transcripts were identified for prepro ET-1 in the lacrimal and Harderian glands. Specific staining for ET-LI was found in the epithelial cells of the ducts of the lacrimal gland and the acinar cells of the Harderian gland. CONCLUSIONS: The higher concentrations of ET-LI in the tears and the lacrimal gland fluid than in plasma along with prepro ET-1 gene transcripts in the tear glands suggest that they secrete ET-1.
The role of temperature and testicular descent in postnatal appearance of inhibitory guanine nucleotide-binding regulatory protein (G(i)) function was studied in the rat testis. Dispersed testicular cells of 5-day-old rats were incubated for 24 h at 32 or 37 C, then for another 24 h at the same temperatures in the presence and absence of pertussis toxin (PT; 100 micrograms/liter), and finally for a third 24-h period with cholera toxin (CT; 500 ng/liter) with or without PT. At both temperatures, PT treatment significantly (P < 0.05) increased the CT-stimulated cAMP output, but had no effect on basal cAMP production. When testosterone (T) production, as an indicator of Leydig cell function, was measured in the same incubation, CT-stimulated T production was greater at 32 C, but PT had no effect at either temperature. A similar finding was made when hCG (10 micrograms/liter), instead of CT, was used as the stimulus of T production. Hence, a functional G(i) protein is present in seminiferous tubules of 5-day-old testes cultured for 3 days at 32 and 37 C, but not in Leydig cells. We then examined the effects of longer exposure of 5-day-old testes to the two temperatures. After culture for 7 days with 0.1 microgram/liter ovine LH, the presence of PT at 32 C significantly (P < 0.01) enhanced CT-stimulated T production during the last 24 h of culture, but the PT effect was not observed when the culture was carried out at 37 C. Hence, G(i)-mediated modulation of Leydig cell function appears to require several days of induction at the lower temperature of 32 C. As the postnatal descent also changes the ambient testicular temperature, we next studied whether this event alters the G(i) protein function of Leydig cells. Five-day-old rats were rendered bilaterally cryptorchid or sham operated, and studied after 12 days. Testis weights did not differ between the abdominal and scrotal testes. In contrast, the basal and hCG-stimulated rates of T production were significantly (P < 0.01-0.05) higher in the scrotal testes. When dispersed cells of the scrotal and abdominal testes were incubated for 24 h at 37 C in the presence of CT with or without PT, enhancement of T production by PT was only observed in cells of the scrotal testes.(ABSTRACT TRUNCATED AT 400 WORDS)
The purpose of the present study was to assess breathing behavior under various nasal resistance load conditions and, in particular, to determine whether respiratory responses to added nasal resistance loads occur before the threshold perception of an added load. The participants were 40 older adults who ranged in age from 59 to 82 years. Nasal airflow and resistance were measured with the pressure-flow technique, which was modified to create calibrated resistance loads. Statistical analyses revealed a significant decrease in airflow rate and volume during load conditions both before perceptual detection and at detection of increased resistance in comparison to a "no load" condition. No differences in respiratory behaviors were found between the load condition just before perceptual detection of an increased resistance load and the load condition at detection. The present findings suggest that physiologic responses to changes in the airway environment apparently occur even before there is perceptual recognition that the environment has changed.
Oral-nasal differential pressures are derived measures that incorporate both active (e.g., articulatory) and passive (e.g., nasal structure) components. This study was designed to examine integrated oral-nasal differential pressures in speakers with different levels of velopharyngeal closure. Integrated oral-nasal differential pressure data were obtained from 20 noncleft adults with normal speech and 166 speakers with repaired palatal clefts. Velopharyngeal competency for the cleft subjects, as determined by aerodynamic assessment, ranged from adequate to grossly incompetent. Results of the data analysis indicate that integrated pressures are not maintained at a consistent level across all groups. This lack of consistency across all degrees of velopharyngeal opening may reflect the flexibility, as well as structural limitations, of a speech pressure regulating system.
The hypothesis that upper airway breathing behaviors generally follow the rules of a physiologic regulating system implies the existence of sensors that monitor the airway environment. The purpose of this study was to assess the sensitivity of the monitoring system to sudden changes in airway patency in healthy, adult subjects. An instrument capable of changing airway dimensions in about 10 ms was used to assess psychophysical recognition and physiologic responses to sudden changes in airway size. Our results indicate that psychophysical recognition of change in patency occurred at a mean constriction area of 0.31 cm2. These findings suggest that recognition of change in airway size occurs well before the airway becomes flow-limiting or severely obstructed.
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PURPOSE: Previous studies have implicated androgens and one or more as yet unknown pituitary or pituitary-dependent factors in the regulation of certain lacrimal gland functions. Many observations suggest that prolactin (PRL) might well be one of these factors. This study was designed to determine the effect of hypophysectomy on biochemical markers of exorbital lacrimal gland secretory capacity and to determine the extent to which dihydrotestosterone (DHT) and prolactin reverse these changes. METHODS: Female rats were hypophysectomized and, 5 days later, were treated for 2 days with DHT (0.25 or 1 mg/kg), PRL (1 or 5 mg/kg), combinations of the low or high doses of DHT and PRL, or vehicle only. The animals were killed, and crude membrane fractions were isolated from their lacrimal glands. An untreated group served as control. RESULTS: Lacrimal glands atrophied rapidly after hypophysectomy, losing 40% of their total and membrane-associated protein and 50% of their total DNA within 5 days. Total Na+,K(+)-ATPase and acid phosphatase activities and beta-adrenergic receptor number were decreased by half, whereas alkaline phosphatase activity and muscarinic cholinergic receptor number were reduced by 25% to 30%. DHT treatment increased total DNA above control values; it partially restored the amount of protein in the gland, the Na+,K(+)-ATPase and acid phosphatase activities, and the beta-adrenergic receptor number; and it fully restored the alkaline phosphatase activity. Prolactin treatment partially restored the amount of protein in the gland and the Na+,K(+)-ATPase activity; it fully restored the alkaline phosphatase activity and cholinergic receptor number; but it had no effect on the acid phosphatase activity or the beta-adrenergic receptor number. The high dose of DHT reduced the increase in cholinergic receptor number elicited by PRL. The high dose of PRL reduced the increases of total Na+,K(+)-ATPase and acid phosphatase elicited by DHT. CONCLUSIONS: These findings suggest that DHT and PRL exert general trophic actions on the lacrimal gland and specifically on lacrimal Na+,K(+)-ATPase, acid phosphatase, and neurotransmitter receptors. They also suggest that excessive levels of either hormone may be deleterious to secretory function. Because sex hormone levels are prone to wide fluctuations in women, our results also suggest a plausible hypothesis to account for the greater incidence in women of lacrimal insufficiency.