Lysosomal glycogen storage disease without deficiency of acid alpha-glucosidase.
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Cathepsin D↗
Biomedical subjects
J Shin
Publications and source records attributed to J Shin.
Intraparenchymal brain metastases: MR imaging versus contrast-enhanced CT.
Prospective and retrospective studies of 75 patients were performed to assess the sensitivities of magnetic resonance (MR) imaging and computed tomography (CT) in the evaluation of suspected intraparenchymal brain metastases. The findings on MR images were equivalent to those on CT scans in 49 of the 75 patients; the remaining findings were discordant in 26 patients, and neither MR imaging nor CT was consistently superior. MR imaging demonstrated more metastases in nine of these 26 patients. However, contrast material-enhanced CT scans were superior in lesion depiction in eight of the 26 patients. Large enhanced lesions that were nearly isointense on MR images were seen well on CT scans. In several cases in which results were discordant, gadolinium-diethylenetriaminepentaacetic acid (DTPA)-enhanced MR images were obtained, and this agent behaved similarly to iodinated contrast agents. If indicated clinically, such as before surgery for a single metastasis, the authors perform both MR imaging and contrast-enhanced CT. Gd-DTPA-enhanced MR imaging may prove to be the method of choice for depiction of intraparenchymal metastases.
Adolescent↗
A single amino acid substitution in an ectopic alpha subunit of a human carcinoma choriogonadotropin.
Human choriogonadotropin [hCG] has two dissimilar noncovalently associated subunits, designated alpha and beta. An ectopically secreted hCG alpha subunit that fails to associate with the beta subunit and displays an anomalously high molecular weight on molecular sieve chromatography but not on sodium dodecyl sulfate-polyacrylamide gel electrophoresis has been sequenced. A single substitution of Glu56 by Ala56 has been found in the altered subunit. No evidence for conformational differences between normal and ectopic alpha could be found using circular dichroism or intrinsic fluorescence as measures of secondary and tertiary structure, respectively. Hydrophobicity profiles as determined by the method of Kyte and Doolittle (Kyte, J., and Doolittle, R. F. (1982) J. Mol. Biol. 157, 105-132) predicted, however, that the hydrophilic segment, Thr54-Ser55-Glu56-Ser57-Thr58, becomes an extension of the preceding hydrophobic segment when Glu56 is substituted with Ala. This solitary hemoglobin S-like mutation may lead to an altered tertiary structure, self dimerization, or an alteration in glycosylation that could be responsible for the ectopic alpha subunit's failure to associate with the beta subunit.
Alanine↗
Disulfides of the lutropin receptor.
Affinity cross-linking of the lutropin receptor with 125I-human choriogonadotropin (hCG) on porcine granulosa cells produced four distinct homone-receptor complexes under reducing conditions. They contain 18-, 24-, 28-, and 34-kDa components (Ji, I., Bock, J. H., and Ji, T. H. (1985) J. Biol. Chem. 260, 12815-12821). Photoaffinity labeling and cross-linking produced 136-, 102-, and 74-kDa hCG-receptor complexes under reducing conditions and the 136-kDa complex under nonreducing conditions. In addition, the unreduced 102-kDa complex was seen in photoaffinity labeling but not in cross-linking. When the unreduced 136-kDa complex was reduced, the 102- and 74-kDa complexes were generated, indicating release of the 34- and the 28-kDa components in two steps. When the unreduced 102-kDa complex was reduced, the 74-kDa complex was produced, indicating the release of a 28-kDa component. The 74-kDa complex could not be reduced but was cleaved by alkaline treatment to produce the hCG alpha beta dimer. The results indicate that the 24-kDa component is released from the 74-kDa complex, since the apparent mass of the hCG alpha beta dimer on gels is 50 kDa. The 24-kDa component appears to be the initial site for photoaffinity labeling or cross-linking and to be disulfide linked to the 28-kDa component which is in turn disulfide linked to the 34-kDa component. These intercomponent disulfides exist in some receptors but not all. Formation of the disulfide-linked 136-kDa band required the presence of a sulfhydryl-blocking agent, N-ethylmaleimide. In particular, the 34-kDa component was vulnerable to reduction. There was no significant evidence of disulfides between the hormone and any of the receptor components.
Affinity Labels↗
Structural homologies in the lutropin/human choriogonadotropin receptor and the follitropin receptor on porcine granulosa cells.
In order to examine the structure of the human choriogonadotropin (hCG) receptor and the follitropin (FSH) receptor on porcine granulosa cells, the hormone receptors were photoaffinity-labeled or affinity-cross-linked. The resulting hormone-receptor complexes were analyzed by alkaline cleavage of cross-links, reduction of disulfides, and peptide maps. The results revealed striking similarities in the structure of the hormone receptors. Both appear to be oligomeric; the hCG receptor has at least four components of 18, 24, 28, and 34 kDa, whereas the FSH receptor shows three distinct components of 18, 22, and 34 kDa. The 24- and the 22-kDa components are the sites for the primary photoaffinity labeling or affinity cross-linking by hCG and FSH, respectively. These components were linked by intercomponent disulfides. Reduction of cross-linked complexes revealed that in the hCG receptor the 24-, the 28-, and the 34-kDa components were disulfide-linked sequentially in a linear form as were the 22-, the 18-, and the 34-kDa components in the FSH receptor. The peptide maps of cross-linked hCG-receptor and FSH-receptor complexes, however, were distinct, indicating that the hCG receptor and the FSH receptor were not identical.
Affinity Labels↗
An electron microscopic study on mast cell degranulation and regeneration in rats.
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Animals↗
Photoaffinity labeling of the follitropin receptor.
A photoactivatable derivative of human follitropin was used to identify the follitropin receptor on porcine granulosa cells. The hormone was condensed with a heterobifunctional reagent, the N-hydroxysuccinimide ester of 4-azidobenzoylglycine, and radioiodinated. The 125I-labeled hormone (125I-hormone) derivative associated with the same number of receptors as 125I-hormone itself, but with a slightly lower Ka, 1.12 X 10(10) M-1 compared with 1.4 X 10(10) M-1 for the 125I-hormone. The binding could be blocked with untreated hormone. Its alpha and beta subunits could be cross-linked to produce alpha beta dimer by photolysis. When the 125I-hormone derivative bound to the cells was photolyzed for crosslinking and the products resolved by electrophoresis on sodium dodecyl sulfate-polyacrylamide gels under reducing conditions, two new bands (106 and 61 kDa) of lower electrophoretic mobility appeared in addition to the alpha, beta, and alpha beta bands. Formation of these crosslinked complexes required photolysis, and the 125I-hormone derivative specifically bound to cells bearing the receptor. Binding could be blocked by excess untreated follitropin but not with human choriogonadotropin and thyrotropin. Under nonreducing conditions, one major band (104 kDa) of cross-linked complexes appeared. Upon reduction with dithiothreitol and second-dimensional electrophoresis, the 104-kDa band produced two smaller complexes of 75 and 61 kDa, indicating the loss of two components and the existence of intercomponent disulfides. Successful production of the 104-kDa complex requires blocking of free sulfhydryl groups with N-ethylmaleimide. It is, however, independent of various protease inhibitors or the temperature and the time period of hormone incubation with cells or the plasma membrane fraction. The mass estimates and the interaction with the hormone of the photoaffinity-labeled components are discussed.
Affinity Labels↗
Composition of cross-linked 125I-follitropin-receptor complexes.
Both of the alpha and beta subunits of intact human follitropin (FSH) were radioiodinated with 125I-sodium iodide and chloramine-T and could be resolved on sodium dodecyl sulfate-polyacrylamide gels. Radioiodinated FSH was affinity-cross-linked with a cleavable (nondisulfide) homobifunctional reagent to its membrane receptor on the porcine granulosa cell surface as well as to a Triton X-100-solubilized form of the receptor. Cross-linked samples revealed three additional bands of slower electrophoretic mobility, corresponding to 65, 83, and 117 kDa, in addition to the hormone bands. The hormone alpha beta dimer band corresponded to 43 kDa. Formation of the three bands requires the 125I-hormone to bind specifically to the receptor with subsequent cross-linking. Binding was prevented by an excess of the native hormone but not by other hormones. A monofunctional analog of the cross-linking reagent failed to produce the three bands. Reagent concentration-dependent cross-linking revealed that their formation was sequential; smaller complexes formed first and then larger ones. When gels of cross-linked complexes were treated to cleave covalent cross-links and then electrophoresed in a second dimension, 18-, 22-, and 34-kDa components were released, in addition to the alpha and beta subunits of the hormone.
Animals↗
Intersubunit disulfides of the follitropin receptor.
The electrophoretic mobility of radioiodinated follitropin (FSH) alpha and beta subunits as well as the alpha beta dimer changed markedly depending on the concentration of reducing agents such as dithiothreitol. The changes were more dramatic in the beta subunit than in the alpha subunit. 125I-FSH, complexed to the receptor on porcine granulosa cells or in Triton X-100 extracts, was cross-linked with a cleavable (nondisulfide) homobifunctional reagent, solubilized in sodium dodecyl sulfate without reducing agents, and electrophoresed. The cross-linked sample revealed three bands of high molecular mass, in addition to the hormone subunit and dimer bands. The band of lightest mass, 110 kDa, was the major band and the other two of 76 and 62 kDa were barely noticeable. Upon reduction with dithiothreitol, the 110-kDa band decreased while the 76- and 62-kDa bands increased, indicating the existence of disulfides between components of the 110-kDa complex. Formation of the disulfide-linked complexes requires 125I-FSH, specifically bound to the hormone receptor and cross-linking, and can be prevented with an excess of native FSH but not human choriogonadotropin. Complex formation was independent of blocking free sulfhydryl groups with N-ethylmaleimide. When the cross-linked complexes were reduced in the gel matrix and analyzed on fresh gels, the 76- and 62-kDa complexes were generated from the 110-kDa band, indicating the loss of two components. The lost components were estimated to be at 14 and 34 kDa. The rate of formation and cleavage of the cross-linked complexes indicated a sequential and incremental addition of 22-, 14-, and 34-kDa components to the FSH alpha beta dimer. The results of reduction of the cross-linked complexes demonstrate the existence of disulfide linkage between the three components.
Animals↗
Radioiodination of a photoactivatable heterobifunctional reagent.
The N-hydroxysuccinimide ester of 4-azidosalicylic acid, a photoactivable heterobifunctional reagent, can be radioiodinated. The low efficiency (3%) of the radioiodination by a previously published method (I. Ji and T. H. Ji, 1982, Anal. Biochem. 121, 286-289) has been increased to 63% by substituting the solvent, acetone, with others such as aqueous acetonitrile, dimethylformamide, or dimethyl sulfoxide. The resulting 125I reagent was used for derivatizing human choriogonadotropin. The radioactive hormone derivative was crosslinked to the alpha beta dimer upon photolysis.
Azides↗
Parathyroid hormone immunoreactivity in the plasma filtrate of uremic patients.
Plasma filtrate of uremic patients concentrated and fractionated by gel filtration consisted of a large peak with C-terminal immunoreactivity and a small peak with N-terminal immunoreactivity. Further analysis of the first peak with C-terminal immunoreactivity by ion exchange chromatography revealed at least 3 peaks indicating the presence of three peaks with a similar immunological behavior but different charge. The elution profile in a patient under chronic hemofiltration was different in pattern compared with that in 2 patients under conventional hemodialysis.
Chromatography, Gel↗
A study on hemodialysis leukopenia using various dialyzers.
Hemodialysis leukopenia was studied using various dialyzers and membranes. We found that dialyzers with cellulosic membranes caused marked leukopenia, but in recently developed non cellulosic membranes, its occurrence was significantly less. Additionally, our results showed a newly developed cellulose acetate membrane to correlate well with the non cellulose membranes regarding leukopenia, in spite of it being a derivative of cellulose. The extent of white blood cell decrease seemed to correlate inversely with an increase in the ultrafiltration rate per membrane area of dialyzer. The relationship between leukopenia and hypoxemia was examined also. The results of this investigation are included, however, we feel that more research is necessary before any conclusions can be made.
Cellulose↗
[Systemic edema, dyspnea, a consciousness disorder, hemiplegia of the right side and proteinuria: (primary systemic amyloidosis)].
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Amyloidosis↗
Adaptation in spiking neurons based on the noise shaping neural coding hypothesis.
Shin, Koch and Douglas [Shin, J., Koch, C., & Douglas, R. (1999). Adaptive neural coding dependent on the time-varying statistics of the somatic input current. Neural Computation, 11, 1983-2003] proposed an adaptive neural coding model that makes spiking neurons adapt its input/output relation to the stimulus statistics. In a surprisingly precise manner, the adaptive neural coding model has been supported by recent experiments. However, the previous report has two problems: (a) although the adaptive neural coding model was developed based on the noise shaping neural coding hypothesis, their connection was not explained clearly in the previous report; and (b) the previous model did not suggest a biologically plausible method to estimate the stimulus mean and variance from spike-evoked intracellular calcium concentration. In this paper, I present how the noise shaping neural coding hypothesis produced such a precise model without any available experimental data at that time. Moreover, I propose a computational model for a biologically plausible signal statistics extraction from spike-evoked intracellular calcium concentration. An asymmetry in contrast adaptation time between increasing and decreasing variance, observed in biological experiments, is explained using the signal statistics extraction method. In addition, a new perspective on the relationship between the spike train of spiking neurons and EEG (or local field potential (LFP)) is suggested based on the noise shaping neural coding hypothesis.
Action Potentials↗
Acid secretion and the H,K ATPase of stomach.
The regulation of acid secretion was clarified by the development of H2-receptor antagonists in the 1970s. It appears that gastrin and acetylcholine exert their effects on acid secretion mainly by stimulation of histamine release from the enterochromaffin-like (ECL) cell of the fundic gastric mucosa. The isolated ECL cell of rat gastric mucosa responds to gastrin/cholecystokinin (CCK), acetylcholine, and epinephrine with histamine release and to somatostatin and R-alpha-methyl histamine by inhibition of histamine release. Histamine and acetylcholine stimulate the parietal cell by elevation of cAMP or [Ca]i by activation of H2 or M3 receptors, respectively. These independent pathways converge to activate the gastric acid pump, the H+,K+ ATPase. Activation is a function of the association of the ATPase with a potassium chloride transport pathway that occurs in the membrane of the secretory canaliculus of the parietal cell. Hence the secretory canaliculus is the site of acid secretion, the acid being pumped into the lumen of the canaliculus. The pump is composed of two subunits, a large catalytic and a smaller glycosylated protein. This final step of acid secretion has become the target of drugs also designed to inhibit acid secretion. The target domain of the benzimidazole class of acid pump inhibitors is the extracytoplasmic domain of the pump that is secreting acid, and the target amino acids are the cysteines present in this domain. The secondary structure of the pump can be analyzed by determining trypsin-sensitive bonds in intact, cytoplasmic-side-out vesicles of the ATPase, and it has been shown that the alpha subunit has at least eight membrane-spanning segments. Omeprazole, the first acid pump inhibitor, forms a disulfide bond with cysteines in the extracytoplasmic loop between the fifth and sixth membrane-spanning segment and to a cysteine in the extracytoplasmic loop between the seventh and eight segments, preventing phosphorylation of the pump by ATP. As a result of the effective and long-lasting inhibition of acid secretion by the acid pump inhibitor, superior clinical results have been found in all forms of acid-related disease.
Amino Acid Sequence↗