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Biomedical subjects

J Du

Publications and source records attributed to J Du.

At least 271 records · Page 15Linked to original sources

[Scavenging effect of EDTA-fluorocarbon microspheres on 210lead].

EDTA-fluorocarbon microspheres (EDTAFM), calcium disodium ethylene diaminetetraacetate (CaNa2EDTA), calcium- or zinc-diethylene triamine pentaacetate (Ca- or Zn-DTPA) were investigated for their ability to treat experimental lead intoxication in mice. The 48 ICR mice were divided into six groups. Group I = no treatment; The other groups were injected with single ip doses of 210Pb (10 mg Pb2+ +555 kBq/kg). After 24 h they were injected in the tail vein with the chelating agents (20 mg/kg) or an equal volume of 10% glucose (10 mg/kg). Each mouse was housed in one metabolic cage, and urine was collected daily for 3 d. After 3 d, the mice were sacrificed for comparison of lead distribution within the liver, kidney, femur and the entire carcass as measured by 0.047 Mev gamma emission from 210Pb. The results reveal that injection of EDTA-FM to lead poisoned mice pretreated with 210Pb was more effective than Zn- or Ca-DTPA and CaNa2EDTA in reducing the lead induced inhibition in the activity of blood ALAD, and that it increased the excretion of 210Pb into the urine. The hepatic, renal and femur 210Pb contents after treatment with EDTAFM were much more decreased than Zn- or Ca-DTPA and CaNa2-EDTA. The order of effectiveness was EDTAFM greater than Zn-DTPA greater than Ca-DTPA greater than CaNa2-EDTA.

Animals↗

The effect of Mg2+ on mitochondrial F0.F1 ATPase and characteristics of the nucleotide binding sites.

The interaction of Mg2+ with nucleotide-washed F0.F1 ATPase from pig heart was studied. Mg2+ had no effect on nucleotide-washed F0.F1 ATPase, but it competitively inhibited the hydrolytic activity of washed F0.F1 ATPase preincubated with ADP and slightly activated the hydrolytic activity of washed F0.F1 ATPase preincubated with ATP. In the last two cases, it revealed negative cooperativity. The effect of Mg2+ on F0.F1 ATPase is therefore closely related to the characteristics of the nucleotide binding sites on mitochondrial F0.F1 ATPase.

Adenosine Diphosphate↗

Chromosomal localization of the gene for the human trifunctional enzyme, methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase.

A trifunctional protein in man, 5,10-methylenetetrahydrofolate dehydrogenase-5,10-methenyltetrahydrofolate cyclohydrolase-10-formyltetrahydrofolate synthetase, catalyzes three consecutive steps in the interconversion of tetrahydrofolate derivatives; these derivatives supply one-carbon units for intermediary metabolism. Somatic cell hybridization and in situ hybridization were used to localize the functional gene coding for this protein--to human chromosome 14q24, near the c-fos and TGF-beta 3 loci. A second hybridizing sequence, possibly a pseudogene, was identified near the centromere of the X chromosome, at Xp11.

Aminohydrolases↗

Cloning and expression of human nebulin cDNAs and assignment of the gene to chromosome 2q31-q32.

We have isolated two nonoverlapping cDNAs encoding human nebulin, a muscle-specific protein. Northern hybridization analysis shows that nebulin is encoded by a huge message at least 25 kb in length. By hybridizing two nonoverlapping cDNAs to DNA isolated from rodent X human cell hybrids, we assign this presumably single-copy gene to human chromosome 2; sublocalization studies indicate that the nebulin gene is on the long arm of the chromosome, in the region 2q31-q32.

Amino Acid Sequence↗

Age-dependent effect of UV light in abnormal alpha neoprotein formation in the lens.

The aim of this study was to determine whether or not alpha neoprotein formation can occur in the lens in response to a photolytic process. Alpha crystallin from young calf and aged bovine lenses was irradiated for up to 22 hours with UV light. After cortical alpha crystallin had been irradiated, it completely preserved its quaternary antigenic determinants. In contrast, 24.3% of the bovine nuclear alpha crystallin completely lost their quaternary determinants as a result of irradiation. The latter population of molecules still preserved the association of A chains with B chains, suggesting the formation of abnormal proteins. The exposure to UV irradiation can cause the formation of alpha neoproteins from aged but not from young alpha crystallin. Comparison of photolytic rates based on spectroscopic and chromatographic parameters also show an age-related increase in the susceptibility of alpha crystallin to photolyze. It is suggested that this increase is due to the age-related formation of a photosensitizer in alpha crystallin.

Aging↗

Chromosomal mapping of genes for transforming growth factors beta 2 and beta 3 in man and mouse: dispersion of TGF-beta gene family.

Human cDNA probes for two new types of transforming growth factor-beta, TGF-beta 2 and TGF-beta 3, were used for mapping their cognate genes on human and mouse chromosomes by Southern blot analysis of somatic cell hybrid lines and, for the human loci, also by in situ chromosomal hybridization. For TGF-beta 2, a single site was found on the long arm of human chromosome 1, band 1q41, and on mouse chromosome 1, most likely in the known conserved syntenic region. For TGF-beta 3, the major site of hybridization, both on Southern filters and direct chromosome preparations, was at 14q24 in humans. This region is homologous in part to mouse chromosome 12, to which the murine beta 3 locus was mapped. These results indicate a wide dispersion of the TGF-beta gene family, with genes for TGF-beta 1 previously mapped by us to human chromosome 19q and mouse chromosome 7 and for inhibins alpha, beta B and beta A to human chromosomes 2q33-qter, 2cen-q13 and 7p15-p13, respectively.

Animals↗

Suckling ability and maternal prolactin levels in hypothyroid rats.

Long-Evans rats and their offspring were made hypothyroid by addition of the antithyroid goitrogen 6-N-propylthiouracil (PTU) to the drinking water (0.1%) from the day of parturition. Serum concentrations of prolactin (PRL), thyroid-stimulating hormone (TSH) and thyroxine (T4) were determined by double radioimmunoassay (RIA). From the fifth postnatal day, body weight of PTU-treated pups was significantly lower than that of control rats, and a strikingly elevated serum TSH level and nondetectable amount of T4 were measured both in PTU-exposed mothers and their offspring at Day 10 postpartum. To test the youngs' suckling capability and the amount of maternal milk production, 10- and 15-day-old normal and PTU-treated pups were separated from their mothers for 4 hr in the morning and then reunited and allowed to suckle. Normal pups gained body weight at the end of both the first and second hour postreunion, while PTU pups gained only during the first hour and lost weight in the second hour of testing. When the pups were exchanged between normal and PTU mothers, opposite results were obtained, indicating that the reduced gain in hypothyroid rats was not due to impaired suckling capability, or insufficient sensory stimulation for milk secretion but to a decreased milk production of PTU mothers. In accordance with this, in lactating hypothyroid rats both the basal (presuckling) level and the suckling-induced rise of serum PRL were found significantly depressed.

Animals↗

Presence of functional NMDA receptors in a human neuroblastoma cell line.

Data are presented that provide convincing evidence for the expression of structurally normal and functional NMDA receptors by acetylcholine-producing human LA-N-2 neuroblastoma cells in culture. Reverse transcription and polymerase chain reaction (RT-PCR), followed by cloning and DNA sequencing, revealed the presence in these cells of mRNA representing the key subunit, NMDAR1, of the receptor. This mRNA was further demonstrated by Northern analysis to be the same size as that described for human neurons. The neutral red cytotoxicity assay was utilized to examine the influence on these neuroblastoma cells of a 48-h incubation with either L-glutamic acid or the specific NMDA agonist N-phthalamoyl-L-glutamic acid (NPG). Cell cytotoxicity was shown by this assay to be increased through incubation with glutamate at 1 and 10 mM by 27 and 37%, and through incubation with NPG at 0.1 and 1 mM by 28 and 46%. A possible mechanism of these toxic effects was further evaluated using the whole-cell configuration of the patch-clamp technique and the specific NMDA agonists (+/-)1-aminocyclobutane-cis-1,3-dicarboxylic acid (ACDA) and NPG. Using this procedure, a voltage-dependent tetrodotoxin-sensitive inward sodium current was found to be increased (x 1.5) by L-glutamic acid and by both NMDA agonists in the presence of glycine. Another voltage-gated inward current, probably carried by calcium ions, was increased three- to fourfold. Hence, these glutamate activities observed in human LA-N-2 neuroblastoma cells appear to occur through the activation of functional NMDA receptors in much the same way as reported for neurons, and both glutamate and NMDA agonists can be toxic to these neuroblastoma cells. Our findings, therefore, suggest this cell line will provide a model suitable for investigating the mechanisms of NMDA-related long-term potentiation (LTP) in neurons and of the NMDA-related neurotoxic effects of glutamate in disease states that involve a reduction in cholinergic function.

Blotting, Northern↗

Asymmetric synthesis of oxazolidine nucleosides and related chemistry.

Asymmetric synthesis of N-substituted oxazolidinyl nucleosides has been accomplished from L-isoserine, trans- and cis-Oxazolidine intermediates (4 and 5) were stereoselectively constructed from N-protected L-isoserine with a menthoxycarbonyl group by the condensation with benzoyloxy acetaldehyde dimethyl acetal in a ratio of 3.9 to 1 in favor of trans-isomer 4. The major isomer 4 was converted to enantiomerically pure beta- and alpha-N-L-menthoxycarbonyl oxazolidinyl thymine nucleosides 11 and 12 in 6 steps.

Antiviral Agents↗

Synthesis of unsaturated carboacyclic nucleoside analogues via Mitsunobu reactions.

2-Substituted allyl alcohols 9 and 14 were prepared starting from butane-1,2,4-triol and glycerol, respectively. Mitsunobu condensations of 9 and 14 with purine and pyrimidine bases, followed by deprotection, afforded a number of acyclonucleosides having 4-hydroxy-2-methylenebutyl or 3,3-bis(hydroxymethyl)-2-methylenepropyl chain.

Alkenes↗

Mechanisms causing muscle proteolysis in uremia: the influence of insulin and cytokines.

Decreased muscle mass in patients with chronic renal failure (CRF) can be caused by mechanisms that activate the ubiquitin-proteasome proteolytic system. This system accelerates the degradation of muscle protein. Concurrent with muscle protein breakdown, there is an increase in transcription of genes encoding components of this pathway, including ubiquitin and subunits of the proteasome. Potential activating signals include metabolic acidosis which stimulates proteolysis in CRF patients and in muscle of rats with CRF by a mechanism involving glucocorticoids. In CRF patients, there is insulin resistance and high circulating levels of tumor necrosis factor and other cytokines. As the ubiquitin-proteasome proteolytic system is activated in acute diabetes and in catabolic conditions associated with high levels of circulating cytokines, these factors could also activate this pathway. Consequently, we examined whether the transcription factor activated by certain cytokines, NF-kappaB, is involved in the transcriptional regulation of subunits of the 26S proteasome complex. The results suggest that cytokines may be involved in the regulation of muscle protein degradation in uremia.

Animals↗

Experimental studies of pancreatic transplantation after freezing and thawing.

The successful rat pancreatic transplantation, after 30 minutes cryopreservation at -80 degrees C, is presented with the normal graft function till the 6th postoperative day maximum. The freezing device used by the authors is shortly described. The choice of optimal freezing and thawing parameters is discussed. Organ freezing is a hopeful method which could serve to preserve the solid organs for a long period of time. Our former experimental research showed that slow freezing (1-2 degrees C/min) and fast thawing (> 100 degrees C/min) had produced less damage to the pancreas of the rat [1]. Recently we performed rat pancreatic transplantation after freezing and thawing the donor pancreas with the parameters mentioned above.

Animals↗