Biomedical subjects

B D Schultz

Publications and source records attributed to B D Schultz.

26 records · Page 2Linked to original sources

PubMed1995

Regulation of CFTR Cl- channel gating by ADP and ATP analogues.

The cystic fibrosis gene product (CFTR) is a chloride channel which, once phosphorylated, is regulated by nucleotide phosphates (Anderson, M. P., and M. J. Welsh. 1992. Science. 257:1701-1704; Venglarik, C. J., B. D. Schultz, R. A. Frizzell, and R. J. Bridges. 1994. Journal of General Physiology. 104:123-146). Nucleotide triphosphates initiate channel activity, while nucleotide diphosphates and nonhydrolyzable ATP analogues do not. To further characterize the role of these compounds on CFTR channel activity we examined their effects on chloride channel currents in excised inside-out membrane patches from CFTR transfected mouse L cells. ADP competitively inhibited ATP-dependent CFTR channel gating with a Ki of 16 +/- 9 microM. AMP neither initiated CFTR channel gating nor inhibited ATP-dependent CFTR channel gating. Similarly, ATP analogues with substitutions in the phosphate chain, including AMPCPP, AMPPCP, AMPPNP, and ATP gamma S failed to support CFTR channel activity when present at the cytoplasmic face of the membrane and none of these analogues, when present at three to 10-fold excess of ATP, detectably altered ATP-dependent CFTR channel gating. These data suggest that none of these ATP analogues interact with the ATP regulatory site of CFTR which we previously characterized and, therefore, no inference regarding a requirement for ATP hydrolysis in CFTR channel gating can be made from their failure to support channel activity. Furthermore, the data indicate that this nucleotide regulatory site is exquisitely sensitive to alterations in the phosphate chain of the nucleotide; only a nonsubstituted nucleotide di- or triphosphate interacts with this regulatory site. Alternative recording conditions, such as the presence of kinase and a reduction in temperature to 25 degrees C, result in a previously uncharacterized kinetic state of CFTR which may exhibit distinctly different nucleotide dependencies.

Adenosine Diphosphate↗

PubMed1994

ATP alters current fluctuations of cystic fibrosis transmembrane conductance regulator: evidence for a three-state activation mechanism.

The cystic fibrosis gene product cystic fibrosis transmembrane conductance regulator (CFTR) is a low conductance, cAMP-regulated Cl- channel. Removal of cytosolic ATP causes a cessation of cAMP-dependent kinase-phosphorylated CFTR channel activity that resumes upon ATP addition. (Anderson, M. P., H. A. Berger, D. R. Rich, R. J. Gregory, A. E. Smith, and M. J. Welsh. 1991. Cell. 67:775-784). The aim of this study was to quantify possible effects of ATP on CFTR gating. We analyzed multichannel records since only 1 of 64 patches contained a single channel. ATP increased the channel open probability (Po) as a simple Michaelis-Menten function of concentration; the effect was half maximal at 24 microM, reached a maximum of 0.44, and had a Hill coefficient of 1.13. Since the maximum Po was not 1, the simplest description of the effect of ATP on CFTR gating is the noncooperative three-state mechanism of del Castillo and Katz (1957. Proceedings of the Royal Society of London. B. 146:369-381). We analyzed current fluctuations to quantify possible changes in CFTR gating. The power density spectra appeared to contain a single Lorentzian in the range of 0.096-31 Hz. Analysis of the corner frequency (fc) of this Lorentzian revealed that ATP increased 2 pi fc as a Michaelis-Menten function with a Hill coefficient of 1.08, and it provided estimates of the ATP dissociation constant (44 tau open (154 ms), and the ATP-sensitive tau close [(185 ms) (44 microM/[ATP] + 1)]. These results suggest that the binding reaction is rapid compared to the opening and closing rates. Assuming that there is a single set of closed-to-open transitions, it is possible to verify the outcome of fluctuation analysis by comparing fluctuation-derived estimates of Po with measures of Po from current records. The two values were nearly identical. Thus, noise analysis provides a quantitative description of the effect of ATP on CFTR opening. The noncooperative three-state model should serve as a basis to understand possible alterations in CFTR gating resulting from regulators or point mutations.

Adenosine Triphosphate↗

PubMed1993

Epinephrine effects on gastrin and gastric secretions in normal and stress-susceptible pigs and in dogs.

1. Epinephrine induced plasma gastrin concentration increased linearly in dogs, and significantly in pigs. 2. Epinephrine induced gastric secretion rate increased in dogs and decreased in pigs, and yet significantly reduced gastric pH only in dogs. 3. Statistical differences in heart and respiratory rate with epinephrine versus saline infusion were detected only in pigs. 4. Stress-susceptible pigs had a significant decrease in gastric secretion pH, heart rate and increased respiration compared to normal pigs, during saline infusion.

Animals↗

PubMed1990

Interpretation of airborne asbestos measurements.

Transmission electron microscopy (TEM) is the preferred method of measuring airborne asbestos in buildings, but TEM measurements cannot be used directly in the existing equations relating risk to exposure because the equations are based on measurements made with a different technique--phase contrast microscopy (PCM). Comparison between measurements made by different methods is not simple because the methods differ in the size of particles they can detect, and the relationship between exposure and disease is thought to depend on, among other things, asbestos fiber size. Previous suggestions for converting TEM measurements to PCM equivalents lack generality because they fail to take into account the size distribution of the asbestos particles and the expectation that fiber-size distributions in current nonoccupational environments could differ from the workplaces of the past on which the risk equations are based. A mathematical model is presented for investigating the conversion of airborne asbestos measurements made by one method to an equivalent measurement made by another method. "Equivalent" means having the same potential to cause disease. The model clarifies the issues of concern and suggests approaches for obtaining meaningful conversion factors that will allow TEM measurements to be used in PCM-based risk equations.

Air Pollutants↗

PubMed1989

Serum chemical profile of feeder pigs, as influenced by market stress and feeding regimen.

Two hundred eighty-eight crossbred feeder pigs were used in 2 trials to determine the effects of feed and/or water deprivation at an auction market, and the effects of restricting the intake of the receiving diet on their serum chemical profile. The study also was designed to assess the value of the serum chemical profile as a diagnostic data base for stress disorders in feeder pigs. Performance data indicated that feeder pigs provided water only at the auction facilities lost significantly more weight than did those provided feed and water. Feeder pigs deprived of both feed and water were not significantly different in body weight from either group. Several serum chemical values (creatinine, triglycerides, cholesterol, blood urea nitrogen, and lactate dehydrogenase) were significantly influenced by feed deprivation, but not by feed and water deprivation. However, only the serum creatinine values were significantly different after the 24-hour posttransport period. There were no significant differences in pig weight or serum chemical values 84 days after pigs had arrived at the finishing unit. The serum chemical profile, widely used in human medicine, appears not to provide a reliable marker for identification of short-term nutritional deprivation, nor for transport stress in feeder pigs.

Animals↗

PubMed1986

Influence of market stress and protein level on feeder pig hematologic and blood chemical values.

One hundred twenty crossbred feeder pigs were used in 2 trials to determine the effects of food and water deprivation at the auction market and the effects of protein levels of receiving diet on blood chemical values. Food- and water-deprived animals had significantly higher packed-cell volume, colloid osmotic pressure, and cortisol values than did nondeprived animals. Total osmolality and plasma triiodothyronine values were significantly lower in deprived animals. Measurable effects of food and water deprivation were no longer apparent by 14 days after arrival at the research facility. Plasma colloid osmotic pressure had a positive linear relationship with increasing dietary protein level and was statistically different among levels of protein fed. Gilts had higher plasma triiodothyronine values than did barrows. Differential WBC ratios were not different between groups. Measurable differences for treatments (food and water deprivation vs food and water access; and level of protein in the receiving diet) were no longer apparent 84 days after pigs had arrived at the finishing unit.

Animals↗

PubMedDate not supplied

The use of composite dust wipe samples as a means of assessing lead exposure.

This study investigated two methods for analyzing composite dust wipes for lead. The term composite means two or more wipes collected from common components in a dwelling that are combined in the field and analyzed as a single sample. Two methods--a modified Environmental Protection Agency (EPA) Method 3050A and a Wisconsin Occupational Health Laboratory (WOHL) method--were selected based on their anticipated ability to handle the added mass of materials and dust expected in a composite. The study used off-the-shelf wipes to prepare single-, two-, and four-wipe samples. Wipes were spiked with a standard reference material at either a low dust loading level or a high level, and three laboratories analyzed the samples using both methods and both flame atomic absorption spectrometry and inductively coupled plasma-atomic emission spectrometry techniques (ICP). Good agreement with known spiked levels was possible using either method; the modified EPA 3050A showed particular promise. When up to four wipes were combined, all three laboratories found that modified EPA Method 3050A resulted in recoveries between 89 and 101% of the known standard. Although it was possible to achieve good agreement with spiked levels using the WOHL method, some difficulties were encountered, particularly when followed by ICP analysis and when using four wipes. The increased time required to digest the multiwipe composites was not proportional to the number of wipes in a composite: the two- and four-wipe composites did not take two to four times as long as a single-wipe sample. Laboratory analysis of a four-wipe sample cost an average of 65% less than analysis of four single-wipe samples for each method.

Analysis of Variance↗

PubMedDate not supplied

Estimated change in blood lead concentration in control populations.

Investigators have conducted several studies to assess the effectiveness of lead hazard interventions in reducing children's blood lead levels. For practical and ethical reasons, many of these studies have not included control populations. It is, therefore, impossible for researchers to determine to what extent the reported decline in blood lead concentrations has resulted from intervention versus other factors. In the current retrospective analysis, the authors estimated the change in children's blood lead levels in control populations at 12-mo follow-up. The results suggest that an average 9% decline may be attributed to factors that are unrelated to intervention. Declines of approximately 25% have been reported following several lead-hazard interventions. For these studies, the results of the authors' analysis suggest that approximately 16% of the decline is attributed directly to the intervention.

Age Factors↗