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Biomedical subjects

D L Williams

Publications and source records attributed to D L Williams.

At least 343 records · Page 19Linked to original sources

Correlations between skin sensitization potential and chemical reactivity for p-nitrobenzyl compounds.

Quantitative relationships between skin sensitization potential and certain physico-chemical properties of alkylating agents have been reported. This study demonstrates the correlation of the relative alkylation index (RAI), derived from the alkylation rate and lipophilicity of an alkylating agent, with a set of experimental sensitization data obtained for a series of p-nitrobenzyl compounds.

Alkylation↗

Test of the assumptions underlying comparative hearing aid evaluations.

Comparative hearing aid evaluations using NU-6 monosyllabic word lists were administered to adults with predominately high-frequency sensorineural hearing impairments who were randomly assigned to one of two experiments. In the first, three instruments were used that were electroacoustically similar and appropriate to the patients' hearing losses. In the second, the three hearing aids employed were electroacoustically quite different. Following an initial comparative hearing aid evaluation, the patients used the instruments during a trial-use week after which they ranked the aids in terms of benefit provided in daily communication. Following the trial-use week, the comparative hearing aid evaluation was repeated. The results suggest that significant interaid performance differences on the hearing aid evaluation are not likely to occur very often when the aids being evaluated are relatively homogeneous electroacoustically. In contrast, when electroacoustically heterogeneous instruments are evaluated, significant performance differences may occur frequently. Under such circumstances, however, the same instrument(s) would likely provide the best performance to most patients. The results further suggest that the reliability of standard monosyllabic word lists may not be adequate to detect typical interaid differences that occur in a comparative hearing aid evaluation and that the performance hierarchy is likely to change as the patient adjusts to amplification. Finally, the comparative hearing aid evaluation will not be a good predictor of success in daily communication unless relatively large performance differences exist among the instruments.

Acoustics↗

Apolipoprotein E synthesis in human kidney, adrenal gland, and liver.

Human tissues were incubated in vitro with radiolabeled amino acids to determine whether plasma apolipoproteins are synthesized in human kidney. Subsequently, tissue extracts were screened with antisera directed against apolipoprotein E (apo E), apolipoprotein B (apo B), apolipoprotein AI (apo AI), and bulk apolipoproteins of high density lipoprotein (HDL). Newly synthesized apo E, but not apo AI or apo B, was identified in kidney and adrenal cortex. Estimates of relative rates of apo E synthesis in vitro suggest that a substantial portion of adrenal and kidney protein synthesis is committed to apo E synthesis. The relative rate of apo E synthesis was 4-6 times greater in kidney cortex than in kidney medulla. Analysis of immunoreactive apo E showed that kidney and adrenal apo E species have the same electrophoretic mobility in NaDodSO4/polyacrylamide gels as does plasma apo E. Further characterization by high resolution two-dimensional gel analysis indicated that the isoforms of newly synthesized kidney and adrenal apo E correspond to specific isoforms of plasma apo E. These findings suggest that apolipoproteins arising from peripheral tissues may play an important role in lipid transport and metabolism.

Adrenal Glands↗

Single-photon emission computed tomography of the normal liver.

Single-photon emission computed tomography (SPECT) is a new imaging method that offers the advantage of cross-sectional imaging and improved contrast resolution as compared with conventional planar imaging. Preliminary SPECT studies of the liver for detection of metastatic disease are very promising. However, these studies indicate some potential pitfalls in the interpretation of the normal liver SPECT images. Experience with 58 tomographic studies obtained with a General Electric 400T rotating gamma camera is presented, with special emphasis on the areas of potential misinterpretation and on recognition of the normal anatomy as seen by this technique.

Elementary Particles↗

Immunotherapeutic modification of Escherichia coli--induced experimental peritonitis and bacteremia by glucan.

Previous data from our laboratory have demonstrated that glucan administration significantly alters the course of a variety of experimentally induced infectious diseases. In view of the increasing incidence of gram-negative infections, studies were initiated to evaluate the effect of intraperitoneal glucan therapy on Escherichia coli-induced peritonitis and sepsis. Male ICR/Tex mice were injected intraperitoneally with glucan or dextrose on days 5 and 3 prior to intraperitoneal challenge with 1.0 x 10(8) E. coli. Glucan administration resulted in a significant enhancement of survival. Evaluation of the mechanism of protective action of glucan revealed that both the glucan and dextrose control groups showed an equivalent level of blood-borne E. coli at early periods. At 6 hours after challenge the glucan group showed a significant decrease in blood-borne E. coli. In contrast, the dextrose control group demonstrated progressive bacteremia. A significant depression of phagocytic activity occurred in E. coli-infected mice as compared with control mice that were not exposed to the bacterial challenge. The enhancement in phagocytic function observed in glucan-treated control mice was unaltered in E. coli challenged, glucan-treated mice. The possible importance of hyperfunctional macrophages in reduction of mortality from E. coli sepsis was denoted by methyl palmitate-induced reversal of the glucan hyperfunctional state. Methyl palmitate-treated glucan injected mice were not protected against E. coli infection. These data denote that the intraperitoneal administration of glucan significantly modifies the course of E. coli-induced peritonitis and bacteremia due, in part, to glucan-induced enhancement of macrophage function.

Animals↗

Effects of particulate beta-1,3 glucan on human, rat, and guinea pig complement activity.

Particulate glucan, a beta-1,3-linked polyglucose derived from Saccharomyces cerevisiae, has been demonstrated to have a wide range of immunopotentiating effects. Glucan administration is associated with the modification of a variety of experimentally induced infectious disease states as well as the inhibition of growth of implantable and spontaneous tumors. The present study was designed to evaluate the effect of glucan upon activation of the complement system in rats and guinea pigs. Additional studies were performed to determine the in vitro activating effect of glucan and zymosan on complement activity of human serum. Glucan activated both the classical pathway of normal human sera and the alternate pathways in C2hu-deficient sera in vitro releasing anaphylatoxins such as C3a. The intravenous injection of glucan activated the alternate pathway of guinea pig plasma. The influence of glucan on complement depletion induced by cobra venom factor (CVF) was also ascertained. Complement activation by glucan may contribute, in part, to the enhanced resistance of the host against tumor growth as well as infectious episodes.

Animals↗

Isolation and characterization of a cDNA clone specific for avian vitellogenin II.

A clone for vitellogenin, a major avian, estrogen responsive egg yolk protein, was isolated from the cDNA library of estrogen-induced rooster liver. Two forms of plasma vitellogenin, vitellogenin I (VTG I) and vitellogenin II (VTG II), distinguishable on the basis of their unique partial proteolysis maps, have been characterized and their corresponding hepatic precursor forms identified. We have used this criterion to specifically characterize which vitellogenin protein had been cloned. Partial proteolysis maps of BTG I and VTG II standards, synthesized in vivo, were compared to maps of protein synthesized in vitro using RNA hybrid-selected by the vitellogenin plasmid. Eight major digest fragments were found common to the in vitro synthesized vitellogenin and the VTG II standard while no fragments were observed to correspond to the VTG I map. A restriction map of the VTG II cDNA clone permits comparison to previously described cDNA and genomic vitellogenin clones.

Animals↗

Biosynthesis of the vitellogenins. Identification and characterization of nonphosphorylated precursors to avian vitellogenin I and vitellogenin II.

Avian vitellogenin consists of two major species designated VTG I and VTG II. Rooster hepatocytes were employed to identify intracellular forms of the vitellogenins and to characterize biosynthetic intermediates of VTG I and VTG II. After labeling with [3H]serine, intracellular vitellogenin radioactivity was seen in mature VTG I and VTG II but was primarily found in two species, pVTG I and pVTG II, which showed greater mobilities in sodium dodecyl sulfate-polyacrylamide gels. The pVTG species were identified as vitellogenins by reaction with antibodies against plasma VTG II and against the mixture of VTG I and VTG II. Immunological and peptide mapping procedures were used to relate pVTG I and pVTG II to secreted VTG I and VTG II, respectively. Pulse-labeling and pulse-chase experiments showed that the pVTG species are precursors to the secreted vitellogenins and are thus discrete intermediates in the biosynthesis of the vitellogenins. Additional labeling experiments showed that the pVTG species are glycosylated but not phosphorylated. The stages of vitellogenin biosynthesis may be ordered as follows: polypeptide synthesis leads to glycosylation leads to phosphorylation leads to secretion. The presence of only small quantities of the phosphorylated vitellogenins intracellularly indicates that when phosphorylation is completed, the vitellogenins are rapidly secreted from the hepatocyte. The differences in the electrophoretic mobilities of the pVTG and VTG species suggested that sodium dodecyl sulfate-polyacrylamide gel electrophoresis does not accurately estimate the molecular weights of the heavily phosphorylated vitellogenins. This was confirmed directly by showing that the mobility of plasma vitellogenin increased upon dephosphorylation. An independent estimate of vitellogenin molecular weight was made by gel chromatography in 7 M guanidine-HCl. With this method, the molecular weights of the pVTG and VTG species were indistinguishable and in agreement with the molecular weight of the pVTG species as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These analyses indicate that the vitellogenin polypeptide has Mr approximately equal to 180,000. This value is 60,000-70,000 less than commonly estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The implications of this lower molecular weight are discussed in relation to vitellogenin structure and the egg yolk polypeptides which may derive from each vitellogenin.

Animals↗

The preparation of thyroid microsomal antigen for use in the indirect micro-ELISA method for the detection of anti-thyroid microsomal autoantibody.

Thyroid microsomes for use in assay systems for anti-thyroid-microsomal antibodies are normally prepared by ultracentrifugation. By means of gel filtration studies we show that preparations made in this way are invariably contaminated with thyroglobulin. A further purification by gel filtration is described which enables the preparation of thyroid microsomes of sufficient purity for use in a micro-ELISA method for the measurement of anti-thyroid-microsomal antibodies. Microsomes prepared in this way would also be suitable for haemagglutination and radioassays, which are also affected by thyroglobulin contamination.

Antigens↗

Single photon tomographic imaging of a standard heart phantom with 201T1: a gamma camera based system.

A standard heart phantom (University of Iowa design), including discrete myocardial walls, a central blood pool, and a 24-cc transmural "cold" defect, was studied with both planar and transverse tomographic imaging. The heart phantom was filled with 201T1 and placed within a cylindrical tank containing water and 201T1 to simulate nonmyocardial background activity from the thorax. The tomographic imaging system used was a commercially available, rotating, large field-of-view gamma camera. Image reconstruction from 64 sampling angles was performed in a nuclear medicine minicomputer system. The percentage activity in the region of the defect (actual activity of 0) contrasted to the normal wall was compared between planar and 1.25-cm transaxial tomographic slices. Defect activity fell to between 65% and 85% of that of the opposing normal wall in planar images, whereas it fell to between 26% and 49% of that of the normal wall in the tomographic images. In most cases, tomographic defect activity was half or less than that in the planar image. The geographic extent of the defect was seen in an appropriate number of tomographic slices; i.e., the geographic 3.2-cm defect length was predominantly seen in three 1.25-cm transverse slices. We conclude that camera-based tomographic systems show promise for improved 201T1 myocardial defect detection and quantitation over conventional planar images.

Heart↗