Function and biosynthesis of polymeric IgA.
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Animals↗
Biomedical subjects
J O Phillips
Publications and source records attributed to J O Phillips.
Automatic postural responses in the cat: responses to headward and tailward translation.
EMG responses, vertical and A-P shear forces and kinematics of "automatic postural responses" to unexpected translational perturbations in the headward and tailward directions were studied in cats. Muscles acting on the major joints of the forelimbs and hindlimbs were studied. Movement of the animals in response to perturbation were highly stereotyped and consisted of two phases: (1) motion of the feet during platform movement while the trunk remained relatively stationary followed by (2) active correction of posture by movement of the trunk in the direction of perturbation. Vertical force changes occurred after the perturbation was well underway (latency 65 ms) and were related to the displacement of the center of mass and active correction of trunk position. Shear forces showed both passive (inertial) and active components and suggested that the majority of the torque necessary for postural correction was generated by the hindlimb. EMG responses in forelimb and shoulder muscles were most correlated with increase in vertical force, showing a generalized co-contraction in tailward translation (when these limbs were loaded) and little activity when the forelimbs were unloaded. EMG responses in hindlimb showed reciprocal activation of agonists and antagonists during perturbation with strong synergies of thigh and foot flexors in tailward translation and thigh and foot extensors in headward translation. The forelimb EMG patterns were most consistent with the conclusion that the forelimb is used primarily for vertical support during perturbation. It was concluded that hindlimb EMG responses were appropriate for both vertical support and performance of the postural correction. The hindlimb muscle synergies observed during translation are the "mirror image" of those observed in humans by other workers.
Animals↗
Properties of immunoglobulin A in serum of individuals with liver diseases and in hepatic bile.
In comparison with normal individuals, sera of patients with alcoholic cirrhosis and other liver diseases had two to four times higher levels of immunoglobulin A and three to ten time higher levels of polymeric immunoglobulin A. The possible participation of the liver in the selective removal of polymeric immunoglobulin A from serum into bile was investigated by analyzing immunoglobulin A in serum and bile specimens obtained from a group of patients with T-tube drainage of the common bile duct. Gel filtration revealed three principal fractions of biliary immunoglobulin A: secretory immunoglobulin A with J chain and secretory component; polymeric immunoglobulin A associated with J chain; and monomeric immunoglobulin A devoid of J chain and secretory component. Secretory component-complexed immunoglobulin A composed only 50% or less of the total biliary immunoglobulin A. In comparison with immunoglobulin G, polymeric forms of immunoglobulin A appeared to be selectively transported into bile whereas monomeric immunoglobulin A was not. These data suggested that the liver selectively transports polymeric immunoglobulin A from serum into bile by both secretory component-dependent and -independent mechanisms.
Aged↗
Biochemical determinants of responsiveness to 5-fluorouracil and its derivatives in xenografts of human colorectal adenocarcinomas in mice.
The level of thymidylate synthetase (EC 2.1.1.45) and its activity have been measured in a series of human colorectal adenocarcinomas growing as xenografts in immune-deprived mice. Enzyme activity varied between 8.4 and 124 pmol per mg protein per hr; within each tumor line, this activity correlated with the capacity to bind [6-3H]5-fluoro-2'-deoxyuridine 5'-monophosphate ([6-3H]FdUMP), which varied between 0.16 and 1.68 pmol [6-3H]FdUMP bound per g tissue. Highest and lowest activities were measured in tumor lines that were insensitive to 5-fluorouracil, 5-fluorouridine, and 5-fluoro-2'-deoxyuridine. The ratio of the maximum free FdUMP concentration to thymidine 5'-monophosphate synthetase-binding activity did not differentiate fluorinated pyrimidine-responsive lines from those innately insensitive. Maximum potential binding of [6-3H]FdUMP in vitro was measured without addition of dl-L-5,10-methylenetetrahydrofolate (CH2FH4) in cytosol from two tumor lines, both of which demonstrated some sensitivity to fluorinated pyrimidine therapy. The other four insensitive tumor lines required CH2FH4 to be added in order to attain maximum [6-3H]FdUMP binding. Similar data were obtained using nitrocellulose membrane filtration to isolate both covalent and noncovalent complexes. Direct measurement of thymidine 5'-monophosphate synthetase activity after incubation of tumor cytosols with FdUMP, with or without added CH2FH4 showed that, in nonresponsive tumors, maximum enzyme inhibition was achieved only in the presence of exogenous cofactor. It is suggested that the availability of cofactor may prove important in the formation of the ternary complex CH2FH4:thymidine 5'-monophosphate synthetase:FdUMP when high concentrations of FdUMP are present for only short periods of time.
Adenocarcinoma↗
The relative rates of protein synthesis and degradation in a growing culture of Escherichia coli.
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Bacterial Proteins↗
Receptor-dependent growth inhibition of human pancreatic cancer by 9-cis retinoic acid.
Pancreatic cancer continues to be a lethal disease and ranks as the fifth major cause of cancer death with a 2-year survival rate of only 8%. Although significant progress has been made in the surgical management of this malignancy, there have been only minimal advances in adjuvant therapy. Based on the lack of effective adjuvant or primary therapy for these patients, we tested the effects of various retinoids (all-trans, 9-cis, and 13-cis retinoic acids) on the growth of several human pancreatic cancer cell lines. Four human pancreatic cancer cell lines, designated PANC-1, ASPC, BxPc, and HPAF, were studied. Three types of retinoic acid were added to subconfluent monolayers of the different cancer cell lines over a range of concentrations (1 to 20 micromol/L). Effects on cell growth were determined daily over 96 hours by a cell proliferation assay (MTT). Nuclear receptor (RAR/RXR) transcript and protein were determined by reverse transcription polymerase chain reaction and Western blot analyses. Three (PANC-1, ASPC, and BxPc) pancreatic cancer cell lines responded in a dose-dependent fashion with a significant decrease in cell growth at clinically relevant concentrations of 9-cis retinoic acid (7.5 to 10 micromol/L). All-trans and 13-cis retinoic acid did not affect cell growth in the four pancreatic tumors.
Alitretinoin↗
The role of the liver in catabolism of mouse and human IgA.
The fate of intravascular IgA which is produced in large quantities in humans and many animal species was investigated in vivo and in vitro with emphasis on the monomeric form of IgA. The site(s) of the catabolism of intravenously injected mouse monomeric IgA labeled with a residualizing tracer (dilactitol - 125I tyramine) was studied in mice. The greatest in vivo uptake of monomeric IgA was observed in the liver. In contrast to identically labeled IgG, liver accounted for more internal catabolism of monomeric IgA than all other tissues (spleen, muscle, skin, and kidney) combined. Although both parenchymal and nonparenchymal liver cells internalized monomeric IgA, hepatocytes were far more active. The uptake of monomeric IgA was primarily mediated by the asialoglycoprotein receptor. In humans, the particulate fraction of liver homogenates and a human hepatoma cell line (Hep G2) bound human IgA proteins of various molecular forms. Inhibition of the binding by desialylated glycoproteins, requirement for the presence of calcium, and the molecular properties of the IgA-binding protein from the plasma membrane of Hep G2 cells indicated that the binding was primarily mediated by the asialoglycoprotein receptor. IgA proteins bound by Hep/G2 cells were internalized and catabolized to low molecular weight fragments.
Animals↗