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Biomedical subjects

C Jung

Publications and source records attributed to C Jung.

At least 181 records · Page 10Linked to original sources

Quantum chemical interpretation of the spectral properties of the CO and O2 complexes of hemoglobin and cytochrome P-450.

The electronic transitions of CO and O2 complexes of hemoglobin and cytochrome P-450 were calculated using a PPP method extended for metal complexes. The calculations show that the unusual spectral properties of cytochrome P-450 are very sensitive to the iron-sulfur bond distance. It is suggested from these calculations that for the conversion of cytochrome P-450 to cytochrome P-420 an increase of the iron-sulfur bond distance of only about 0.2 A is sufficient. The anomalous Soret band of the CO complex as well as the normal Soret band of the O2 complex of cytochrome P-450 are explicable assuming a mercaptide sulfur as fifth ligand.

Animals↗

Cation metabolism in relation to cell size in synchronously grown tissue culture cell.

In randomly grown tissue culture cells (mouse leukemic lymphoblast, L5178Y) the number, volume, and Na(+) and K(+) content increase as an exponential function with a doubling time of 11.3 hr. In synchronously grown cells the volume increase of the population and of single cells follows the same exponential function as in randomly grown cells. In contrast, the cation content fluctuates during a single cell cycle. About 1(1/2) hr after the cell division burst (at the beginning of the S period), a net loss of K(+) occurs for a period of about 1 hr amounting to about 20% of the total K. Over the next 5 to 6 hr, the deficit in K(+) is eliminated. The Na(+) content shows a double fluctuation. It falls during the cell division burst, rises when the K(+) content decreases, falls again when K(+) content rises, and then increases again before the next cell division burst. The net fluxes of both Na(+) and K(+) are very small compared to the unidirectional fluxes (less than 5%), thus small changes in the balance of influx and efflux account for the changes in cation content during the growth cycle. Both unidirectional fluxes increase dramatically (by a factor of two) about 2 hr after the cell division burst, and then remain constant until after the next cell division. The pattern of electrolyte regulation during cell division does not follow a simple function such as cell number, cell surface, or cell volume, but must be related to specific internal events in the cell.

Animals↗

Insight into protein structure and protein-ligand recognition by Fourier transform infrared spectroscopy.

An overview of the application of Fourier transform infrared spectroscopy for the analysis of the structure of proteins and protein-ligand recognition is given. The principle of the technique and of the spectra analysis is demonstrated. Spectral signal assignments to vibrational modes of the peptide chromophore, amino acid side chains, cofactors and metal ligands are summarized. Several examples for protein-ligand recognition are discussed. A particular focus is heme proteins and, as an example, studies of cytochrome P450 are reviewed. Fourier transform infrared spectroscopy in combination with the various techniques such as time-resolved and low-temperature methods, site-directed mutagenesis and isotope labeling is a helpful approach to studying protein-ligand recognition.

Cytochrome P-450 Enzyme System↗

Aluminum inhibits neurofilament assembly, cytoskeletal incorporation, and axonal transport. Dynamic nature of aluminum-induced perikaryal neurofilament accumulations as revealed by subunit turnover.

The mechanism by which aluminum induces formation of perikaryal neurofilament (NF) inclusions remains unclear. Aluminum treatment inhibits: 1. The incorporation of newly synthesized NF subunits into Triton-insoluble cytoskeleton of axonal neurites; 2. Their degradation and dephosphorylation; 3. Their translocation into axonal neurites. It also fosters the accumulation of phosphorylated NFs within perikarya. In the present study, we addressed the relationship among these effects. Aluminum reduced the assembly of newly synthesized NF subunits into NFs. During examination of those subunits that did assemble in the presence of aluminum, it was revealed that aluminum also interfered with transport of newly assembled NFs into axonal neurites. Similarly, a delay in axonal transport of microinjected biotinylated NF-H was observed in aluminum-treated cells. Aluminum also inhibited the incorporation of newly synthesized and microinjected subunits into the Triton-insoluble cytoskeleton within both perikarya and neurites. Once incorporated into Triton-insoluble cytoskeletons, however, biotinylated subunits were retained within perikarya of aluminum-treated cells to a greater extent than within untreated cells. Notably, these subunits were depleted in the presence and absence of aluminum within 48 h, despite the persistence of the aluminum-induced perikaryal accumulation itself, suggesting that individual NF subunits undergo turnover even within aluminum-induced perikaryal accumulations. These findings demonstrate that aluminum interferes with multiple aspects of neurofilament dynamics and furthermore leaves open the possibility that aluminum-induced perikaryal NF whorls may not represent permanent structures, but rather may require continued recruitment of cytoskeletal constituents.

Aluminum↗

Characterization of lidocaine metabolism by rat nasal microsomes: implications for nasal drug delivery.

Lidocaine has been recently approved for use as an intranasal spray in the treatment of migraine. In this study, we investigated the metabolism of lidocaine to its primary metabolite monoethylglycine xylidide (MEGX), by rat nasal olfactory and respiratory microsomes. The metabolic parameters were compared with metabolism employing rat and human hepatic microsomes. The olfactory and respiratory microsomes both exhibited considerable activity for conversion of lidocaine to MEGX in comparison with the activity in the hepatic tissues. The rat olfactory microsomes had a markedly higher affinity than the rat hepatic or respiratory microsomes. However, the turnover rate was only about one-half that of rat liver. Employing Western immunoblotting we investigated the presence of cytochrome P450s (CYPs) 1A2, 3A2, 2B1 and 2C11 in rat nasal tissues; these isozymes are known to partcipated in the metabolism of lidocaine in rat liver. These isozymes were found to be present in significant amounts in both the nasal olfactory and respiratory tissue; this is the first known report of the presence of CYP2C11 in nasal mucosae. Our studies underscore the importance of CYP-mediated drug metabolism in nasal tissues. The effect of this 'nasal first-pass' should be weighed carefully while considering the fate and the bioavailability of drugs delivered via the intranasal route.

Anesthetics, Local↗

Arabinogalactan for hepatic drug delivery.

Arabinogalactan, a polysaccharide from the tree Larix occidentalis, has been purified and its biological and physical properties described. Intravenous injection of radiolabeled arabinogalactan (4 mg/kg) in rats resulted in 52.5% of the dose being present in the liver, while prior injection of asialofetuin (100 mg/kg) reduced hepatic radioactivity to 3.54%. Gel chromatography indicates arabinogalactan is a single species of 19 kDa, while light scattering gave a molecular weight of 40 kDa. Glycosyl linkage analysis of arabinogalactan is consistent with a highly branched structure comprising a backbone of 1,3-linked galactopyranose connected by 1,3-glycosidic linkages, comprised of 3,4,6-,3,6-, and 3,4- as well as 3-linked residues. In the carbon-13 NMR spectra, the major resonances of arabinogalactan are assigned to beta-galactopyranose, beta-arabinofuranose, and beta-arabinopyranose. Arabinogalactan produced no adverse reactions in single intravenous dose (mouse, 5000 mg/kg) and repeat dose toxicity studies (rats, 500 mg/kg/day, 90 days). When tritiated arabinogalactan was injected, radioactivity cleared from the liver with a half-life of 3.42 days. Arabinogalactan has properties that make it suitable as a carrier for delivering diagnostic or therapeutic agents to hepatocytes via the asialoglycoprotein receptor.

Animals↗

Conjugation of adenine arabinoside 5'-monophosphate to arabinogalactan: synthesis, characterization, and antiviral activity.

A conjugate consisting of the antiviral nucleotide analogue adenine arabinoside 5'-monophosphate (araAMP, vidarabine monophosphate) and the naturally occurring polysaccharide arabinogalactan was synthesized. The conjugate consisted of 7.9 araAMP residues per molecule of arabinogalactan. The proposed structure of the conjugate was consistent with 13C NMR spectroscopic studies. Daily injections of the conjugate, at a dose of 3 mg of araAMP/kg, into woodchuck carriers of woodchuck hepatitis virus (WHV) decreased serum levels of WHV DNA. A dose of 3 mg/kg of unconjugated araAMP was ineffective, while a higher dose of araAMP (15 mg/kg, 14 days) produced a drop in WHV DNA. After cessation of dosing with the conjugate, serum viral DNA levels remained depressed for 42 days. In contrast, after cessation of dosing with araAMP, WHV DNA rapidly returned to original levels.

Animals↗

Effect of penicillin G on corium thickness in linear morphea of childhood: An analysis using ultrasound technique.

Linear morphea is the most common form of localized scleroderma in children. The pathogenesis of this disorder is unknown. We report a child with a 6-year history of linear morphea in whom intravenous administration of 5 MU aqueous penicillin G three times a day for 10 consecutive days caused reduction in the thickness of the corium as demonstrated by ultrasound measurements.

Child↗