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Biomedical subjects

J M Snyder

Publications and source records attributed to J M Snyder.

At least 55 records · Page 3Linked to original sources
PubMed1988

Progression of hearing loss in bilateral Menière's disease.

Otologists may be reluctant to perform labyrinthectomy in unilateral Menière's disease, fearing the later development of bilateral disease and severe hearing loss in the previously normal ear. To illuminate this issue, we reviewed audiologic records for 85 patients diagnosed as having bilateral Menière's disease at the University of Washington Hospital from 1969 to 1986. The progression of hearing loss in each ear was noted, as well as interaural relationships. Nine patients experienced a significant reversal, in which the initially better ear surpassed the other ear in hearing deficit, but only one of these patients could at any time have been considered a labyrinthectomy candidate, according to hypothetically liberal audiometric criteria.

Adult↗
PubMed1987

Induction and characterization of the major surfactant apoprotein during rabbit fetal lung development.

Antibodies directed against the major apoprotein associated with rabbit lung surfactant were used to characterize the induction and cellular localization of this protein during rabbit fetal lung development. In lung tissues from rabbits of 26 days gestational age and older, discrete epithelial type II cells were stained positively using the peroxidase antiperoxidase technique. The content of the major protein in homogenates of fetal lung tissue was analyzed using an immunoblotting technique. A protein of about 29 kDa, pI less than or equal to 5.6, was first detectable in fetal lung tissue on day 24 of gestation. The 29-36 kDa, mature form of the surfactant apoprotein was first detectable in lung homogenates from 30-day gestational age fetal rabbits. Treatment of homogenates of day 26 and 31 fetal lung tissues with endoglycosidase F, yielded, in both cases, an immunoreactive triplet with more neutral isoelectric points than the proteins in the untreated homogenates. By immunoblot analysis, we found that only the 29-36 kDa, mature form of the surfactant apoprotein was present in lamellar bodies purified from lung tissues of fetuses of 28 and 31 days and from day 2 neonates. These findings are suggestive that only the mature, 29-36 kDa form of the surfactant apoprotein is associated with lamellar bodies during fetal lung type II cell differentiation in vivo.

Animals↗
PubMed1987

Localization and accumulation of fibronectin in rabbit fetal lung tissue.

An interaction between mesenchyme and epithelium is required for the normal differentiation of fetal lung tissue. This morphogenic interaction may be mediated, in part, by changes in the composition and/or structure of the extracellular matrix. Therefore, we characterized the localization and accumulation of fibronectin, an extracellular-matrix component, during several stages of lung development in the rabbit fetus in vivo as well as in day-21 rabbit fetal lung explants maintained in vitro. Fibronectin was detected immunocytochemically in the basement-membrane zone beneath the epithelial ducts in lung tissue obtained from rabbit fetuses at 19 and 21 days of gestation. In fetal lung tissue obtained at these early stages of lung development, mesenchymal cells were stained only at their periphery. Immunostaining for connective-tissue fibronectin increased greatly between days 24 and 31 of gestation. A similar increase in the intensity of immunostaining for connective-tissue fibronectin was observed in rabbit fetal lung explants that had been maintained in vitro for 7 days. The concentration of fibronectin in fetal lung tissue obtained at different days of gestation was determined using a specific enzyme-linked immunoadsorbent assay (ELISA) and was found to increase from 1.7 ng/micrograms protein in fetal lung tissue obtained at day 19 of gestation to 7.3 ng/micrograms protein in fetal lung tissue obtained at day 24 of gestation. The levels of fetal lung fibronectin then remained relatively constant through to day 31 of gestation. A similar increase in fibronectin concentration was observed in day-21 fetal lung explants maintained in vitro for 7 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Failure to detect a stimulatory effect of estradiol-17 beta on ovine fetal lung maturation.

It has been reported that estradiol-17 beta (E2) stimulates rat and rabbit fetal lung maturation; however, E2 was not directly administered to the fetus in these experiments. Therefore, we used the chronically instrumented fetal sheep to study the effects of 14 days of continuous E2 infusion on fetal lung maturation. Animals were instrumented on days 104-106 of gestation, then infused with either saline or E2 (100 micrograms/day) from 111 to 127 days of gestation. Fetal plasma concentrations of E2, estrone, and cortisol, and tracheal fluid phosphatidylcholine:sphingomyelin ratios and phosphatidylcholine flux were measured daily in E2-infused (n = 8) and saline-infused (n = 6) control animals. At 127 days of gestation, fetuses were sacrificed and lung tissue samples obtained for biochemical and morphological analyses. Plasma E2 levels rose from 0.045 +/- 0.001 (mean +/- SE) to 7.45 +/- 5.31 ng/ml (p less than 0.05) in E2-infused animals whereas levels remained less than 0.06 ng/ml in saline-infused animals. Plasma estrone concentrations also were significantly elevated by E2 infusion. Plasma cortisol concentrations increased from 0.58 +/- 0.08 to 0.88 +/- 0.40 microgram/dl in E2-treated fetuses during the last week of infusion whereas values in control animals were unchanged. The ratio of acetone-precipitated phosphatidylcholine to sphingomyelin and the flux of acetone-precipitated phosphatidylcholine in tracheal fluid were not affected by E2 infusion. Fetal lung tissue phospholipid content was also unaffected by E2 infusion. Furthermore, there was no consistent effect of E2 infusion on the histological structure of the fetal lung tissue as determined by morphometric methods.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Insulin inhibits the accumulation of the major lung surfactant apoprotein in human fetal lung explants maintained in vitro.

In the present study, we characterized the proteins associated with a purified lamellar body fraction isolated from human fetal lung explants. We then raised antibodies directed against the major human surfactant apoprotein, a 35-K glycoprotein, and used the technique of immunoblot analysis to evaluate the content of the surfactant apoprotein in human fetal lung explants maintained in serum-free medium in vitro. We found that the 35K surfactant apoprotein was undetectable in homogenates of fetal lung tissue before culture; the surfactant apoprotein was induced in the cultured explants coincident with the appearance of differentiated type II cells. Insulin, at concentrations as low as 2.5 ng/ml, caused marked inhibition of the accumulation of the 35K protein in the cultured fetal lung tissue. The inhibitory effect of insulin was dose dependent and was apparent as early as day 2 of incubation. When explants were cultured in medium containing insulin plus cortisol, the amount of immunoreactive surfactant apoprotein was reduced compared to that of explants cultured in control medium or explants cultured with cortisol alone. On the other hand, as reported previously, insulin and cortisol, in combination, stimulated phosphatidylcholine synthesis. These findings are indicative that the phospholipid and apoprotein components of surfactant are regulated independently. The results of our studies suggest that fetal hyperinsulinemia may cause the production of a surfactant deficient in the 35K apoprotein, and this may provide an explanation for the increased incidence of respiratory distress syndrome in infants of diabetic mothers.

Apoproteins↗
PubMed1987

Adenosine 3',5'-monophosphate analogs and beta-adrenergic agonists induce the synthesis of the major surfactant apoprotein in human fetal lung in vitro.

The use of beta-adrenergic agonists in the treatment of preterm labor has been found to be associated with a decreased incidence of respiratory distress syndrome (RDS) in premature newborns. beta-Sympathomimetic agents, which activate adenylate cyclase and increase tissue cAMP levels, as well as cAMP analogs stimulate surfactant glycerophospholipid synthesis and secretion by fetal lung tissue. In the present study, we used antibodies directed against the major human pulmonary surfactant apoprotein, a 35,000-dalton glycoprotein, to evaluate the effects of the cAMP analog dibutyryl cAMP (Bt2cAMP) and the beta-adrenergic agonist terbutaline on surfactant apoprotein synthesis in human fetal lung explants in organ culture. By use of immunoblot analysis, we found that Bt2cAMP (1 mM) markedly stimulated accumulation of the major surfactant apoprotein in human fetal lung explants, as did terbutaline. Bt2cAMP treatment also increased the relative rate of incorporation of [35S]methionine into the major surfactant apoprotein. The Bt2cAMP-induced increase in surfactant apoprotein synthesis and accumulation was associated with an increase in the levels of translatable surfactant apoprotein mRNA. Morphometric analysis at both the light and electron microscopic levels was used to evaluate the effects of Bt2cAMP on the morphology of the human fetal lung in vitro. After 48-h incubation with Bt2cAMP, the prealveolar ducts of the fetal lung explants were enlarged greatly, and the relative amount of interalveolar connective tissue was reduced compared to those in control tissues. The volume density of type II cells in the Bt2cAMP-treated explants was significantly greater than that in control explants at this time point; however, after 4 and 6 days of incubation, the volume density of type II cells in control and Bt2cAMP-treated tissues was similar, and the lumina of the prealveolar ducts of control tissues had a volume density similar to that of Bt2cAMP-treated explants. Bt2cAMP also had pronounced effects on the ultrastructural morphology of the human fetal lung explants. Large quantities of secreted lamellar bodies and tubular myelin were observed in the lumina of the prealveolar ducts of the Bt2cAMP-treated tissue. Few lamellar bodies and no tubular myelin were observed in the lumina of the prealveolar ducts of control tissues. These findings suggest that cAMP may serve an important regulatory role in the synthesis and secretion of the major surfactant apoprotein by human fetal lung.

1-Methyl-3-isobutylxanthine↗
PubMed1987

Somatomedin C/insulin-like growth factor I production by human fetal lung tissue maintained in vitro.

The production of somatomedin C/insulin-like growth factor I (Sm-C/IGFI) by human fetal lung tissue maintained in vitro was examined in the present study. We have shown that epithelial cells in human fetal lung explants maintained in vitro differentiate into type II cells within 4-6 days. During the first 24 h of culture, the fetal lung explants released 2.74 +/- 0.14 ng Sm-C/IGFI/mg tissue protein into the culture medium. At this time the explants contained 0.24 +/- 0.02 ng Sm-C/IGFI/mg tissue protein. During the next 4 days of culture, explant Sm-C/IGFI content and the rate of Sm-C/IGFI secretion into the medium declined by approximately 50%. Sm-C/IGFI secretion was inhibited significantly when fetal lung explants were cultured in media that contained cortisol (10(-7) M), a hormone that is known to stimulate fetal lung type II cell differentiation. The effect of cortisol was both concentration- and time-dependent. While insulin, bovine prolactin, and human growth hormone had no apparent effect on Sm-C/IGFI production by the explants, human prolactin and human placental lactogen both decreased Sm-C/IGFI production. These findings are unprecedented and are suggestive that Sm-C/IGFI synthesis may be regulated in a unique fashion in the fetal lung. The decline in Sm-C/IGFI production by fetal lung tissue temporally correlates with the initiation of fetal lung type II cell differentiation in the human fetal lung explants.

Culture Techniques↗
PubMed1986

Characterization of the physical interaction between antigen-specific B and T cells.

It has been assumed that physical interaction between B cells and helper T cells in the presence of specific antigen is an early and essential step in the physiologic antibody response to thymus-dependent antigens. The present studies were designed to examine this physical interaction by employing carrier-specific T hybridoma cells that can provide help to highly enriched hapten-binding B cells. Direct conjugation of the B and T cells can be visualized at both the light and electron microscopic level and the number of conjugates can be directly quantified. Before their effective conjugation with T cells, the B cells must be incubated with specific antigen for 4 to 6 hr. After this time, the T cells form conjugates with the B cells within 5 min. Conjugate formation requires hapten specificity, carrier specificity, covalent linkage between hapten and carrier, and is MHC restricted. Two types of T-B conjugates were observed by electron microscopy: an antigen-independent attachment of B cell microvilli to small portions of the T cell surface and an antigen-dependent, intimate apposition of large areas of the plasma membranes of the T and B cells. The kinetics of development of the two modes of interaction suggest that the second type may be important for signal transduction, since the number of T and B cells showing intimate interactions increases with time. Monoclonal antibodies directed against Thy-1.2, LFA-1 alpha, L3T4, and I-A partially block conjugation of the two cell types, suggesting that these surface molecules are involved in T-B interaction.

Animals↗
PubMed1986

Regulation of the synthesis of the major surfactant apoprotein in fetal rabbit lung tissue.

Antibodies directed against the major apoprotein of rabbit lung surfactant, a 29-36-kDa glycoprotein, were used to study changes in the levels of translatable surfactant apoprotein mRNA in rabbit lung tissue during development, as well as the effects of cortisol and cyclic AMP analogues on the levels of surfactant apoprotein and its mRNA in fetal rabbit lung tissue in organ culture. The major surfactant apoprotein and its mRNA were undetectable in lung tissues of 21-day gestational age fetal rabbits. Translatable mRNA specific for the major surfactant apoprotein was first detectable in lung tissues of 26-day fetuses, increased 25-fold on day 28, reached peak levels at day 31, and declined after birth. Incubation of 21-day fetal rabbit lung explants with cortisol in serum-free medium resulted in an increase in the specific content of the 29-36-kDa apoprotein. Cyclic AMP analogues and forskolin, an activator of adenylate cyclase, also caused a marked increase in the accumulation of surfactant apoprotein. When fetal lung explants were incubated with cortisol and dibutyryl cyclic AMP in combination, the specific content of the surfactant apoprotein was increased to levels greater than that of explants treated with either cortisol or dibutyryl cyclic AMP alone. These effects of dibutyryl cyclic AMP and cortisol on surfactant apoprotein accumulation were associated with comparable changes in the levels of translatable surfactant apoprotein mRNA. Thus, we have shown for the first time that the induction of pulmonary surfactant apoprotein synthesis during differentiation in vitro and in vivo is associated with an increase in the level of translatable mRNA and that cortisol and cyclic AMP increase both the accumulation of the major surfactant apoprotein and the corresponding mRNA in fetal rabbit lung tissue in vitro.

Animals↗
PubMed1986

Characterization of human pulmonary endocrine cells maintained in vitro.

Endocrine cells located in the epithelium of human fetal airways contain the amine, 5-hydroxytryptamine (5HT), and the peptide, bombesin (BOM), but difficulties in studying these cells experimentally have slowed progress in understanding their functional roles. This investigation describes an in vitro method to maintain pulmonary neuroendocrine cells (PNEC) in organ culture. Bronchial trees from human fetal lungs were dissected free of adherent blood vessels and lung tissue. Explants of the airways were placed in culture dishes containing defined tissue culture medium for five days. Using indirect immunofluorescence, 5HT- and BOM-like immunoreactive cells were observed both in nonincubated airways and in explants maintained for five days in organ culture. The number of 5HT-immunoreactive cells/0.1 mm2 of airway epithelium was not significantly different in the two groups, although there was a significant reduction in 5HT content measured by HPLC after the five-day culture period. The diameter of dense core vesicles and the number of dense core vesicles/micron2 of endocrine cell cytoplasm in cultures were not significantly different from non-incubated controls. Treatment of the explants with the 5HT-synthesis inhibitor p-chlorophenylalanine resulted in a significant reduction both in the number of 5HT-containing cells/0.1 mm2 of airway epithelium and in the 5HT content. These results demonstrate that both 5HT and BOM content in endocrine cells of explants from human fetal airways can be well maintained in organ culture for at least 5 days and that they are responsive to pharmacologic inhibition of 5HT synthesis.

Bombesin↗
PubMed1985

Effect of cortisol on the synthesis of lamellar body glycerophospholipids in fetal rabbit lung tissue in vitro.

The effect of cortisol on the rate of choline incorporation into tissue phosphatidylcholine was investigated in lung explants from fetal rabbits of 19-28 days gestational age. The explants were incubated in medium with or without fetal calf serum for up to 7 days. When lung tissues were incubated in serum-free medium, a stimulatory effect of cortisol on tissue phosphatidylcholine synthesis was found in explants from 21-, 24-, 26- and 28-day fetal rabbits; a stimulatory effect of cortisol was observed in 19-day fetal lung explants only if fetal calf serum was present in the culture medium. To assess directly the effect of cortisol on the synthesis of lamellar body phosphatidylcholine, choline incorporation into phosphatidylcholine associated with a purified lamellar body fraction isolated from lung explants of 21- and 28-day fetal rabbits was also investigated. Cortisol caused a marked stimulation of synthesis and accumulation of lamellar body phosphatidylcholine in lung explants from both 21- and 28-day fetal rabbits. The magnitude of the stimulatory effect of cortisol on the rate of synthesis of lamellar body phosphatidylcholine was always greater than the effect of cortisol on the rate of choline incorporation into lipids of tissue homogenates. The relative rates of synthesis of lamellar body phosphatidylinositol and phosphatidylglycerol were also significantly altered in lung explants from 21- and 28-day fetal rabbits by cortisol treatment. Lamellar bodies that were formed initially in the fetal lung explants were enriched in phosphatidylcholine and phosphatidylinositol and had a relatively low phosphatidylglycerol content. With cortisol treatment there was a decrease in the relative rate of synthesis of lamellar body phosphatidylinositol and an increase in the relative rate of synthesis of phosphatidylglycerol. The stimulatory effect of cortisol on the synthesis of lamellar body phosphatidylcholine was observed at an earlier time-point of incubation than was the effect of cortisol on the relative rates of synthesis of lamellar body phosphatidylinositol and phosphatidylglycerol. The temporal sequence of the cortisol-induced changes in the synthesis of lamellar body glycerophospholipids, therefore, reflects that which occurs with maturation in vivo.

Animals↗
PubMed1984

Maintenance and characterization of human myometrial smooth muscle cells in monolayer culture.

Human myometrial cells were dispersed from uterine tissue by limited enzymatic digestion of myometrium that was obtained at the time of hysterectomy. The dispersed myometrial cells that are obtained in this manner can be maintained in monolayer culture in the presence of medium that contains fetal bovine serum. In primary culture, as well as after passage, the characteristics of these cells are morphologically and biochemically similar to those of smooth muscle cells and myometrial tissue.

Cells, Cultured↗
PubMed1984

Cochlear summating potential recorded from the external auditory meatus of normal humans. Amplitude-intensity functions and relationships to auditory nerve compound action potential.

The summating potential (SP) and the auditory nerve compound action potential (AP) of the electrocochleogram were recorded from the external auditory meatus (EAM) of 10 normal subjects in response to alternating rarefaction and condensation clicks at 90-120 dB pe SPL. Both logarithmic and power functions suggested a similar strength of relationship between SP amplitude and stimulus intensity in each subject. However, a power function represented a more appropriate model of this relationship for the whole set of subjects than did the logarithmic function. Individual power function exponents varied from 0.35 to 0.56 with a weighted average of 0.46 and a S.E. of 0.03. By contrast, because of major heterogeneity of individual slopes at the high stimulus intensities eliciting EAM-measurable SPs, neither the logarithmic nor the power model provided a common description of the relationship between AP voltage and click strength for all subjects. Remarkable inter-individual variability also characterized the relationships between SP and AP amplitudes at various intensity levels and between the SP/AP amplitude ratio and click intensity. The lawful behavior of SP amplitude with varying click strength indicates that, in appropriate circumstance, non-invasive recordings from the ear canal of normal humans provide quantitative information on certain states of activity of cochlear receptors.

Action Potentials↗
PubMed1984

Right pulmonary artery--left atrial communication. A case report and literature review.

A 22-month-old girl with Down's syndrome with a direct communication between the right pulmonary artery and left atrium leading to systemic desaturation is presented. She also had an atrial septal defect of the secondum type, which spontaneously closed. She underwent successful ligation of the abnormal communication. The literature is reviewed and, considering the high incidence of cerebral and systemic emboli, early surgical intervention is recommended.

Blood Pressure↗
PubMed1983

Characterization of rabbit surfactant-associated proteins.

In the present study, the apolipoproteins associated with a purified surfactant fraction isolated from lung lavage of adult rabbits were characterized. Surfactant purity was assessed by the glycerophospholipid composition and by electron microscopic examination. The purified surfactant was delipidated and the apolipoproteins were analyzed by two-dimensional polyacrylamide gel electrophoresis. By use of this technique at least eight proteins or families of proteins were found to be associated with surfactant. Four of these apolipoproteins were families of proteins of 55-70, 29-36, 26-28 and 22-23 kilodaltons (kDa). All of these apolipoprotein families had acidic isoelectric points (pI less than or equal to 5.6), and were specifically bound to a Con A-Sepharose matrix, indicative that these apolipoprotein families are modified by oligosaccharide side-chains. The finding that neuraminidase treatment degraded the 29-36 kDa family is suggestive that this apolipoprotein family contains sialic acid residues. Three major proteins of 66, 43-45 and 35 kDa and a minor protein of 86 kDa were also observed. These proteins had isoelectric points in the more neutral range (pI 6.0-6.5). The 66 kDa protein (pI 6.4) had the same apparent molecular weight and isoelectric point as the major protein of delipidated rabbit serum and as purified rabbit albumin, which suggests that this protein is albumin. These findings are indicative that the apolipoproteins of surfactant are more numerous and complex than previously reported.

Animals↗