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Biomedical subjects

L Gu

Publications and source records attributed to L Gu.

At least 127 records · Page 7Linked to original sources
PubMed1994

Chromosomal assignment of 11 loci in the rat by mouse-rat somatic hybrids and linkage.

Eleven rat genes have been assigned to rat chromosomes by use of mouse x rat somatic hybrids and/or use of linkage to known chromosome markers. Among them, the genes for the inducible nitric oxide synthase (Nos2) and for a vasoactive intestinal peptide receptor (Vipr) are potential candidates for genetic regulation of blood pressure and were localized to rat Chromosomes (Chrs) 10 and 8 respectively. Genes for gastric H,K-ATPase alpha subunit (Atp4a), Class I alcohol dehydrogenase (Adh), and aldolase C (Aldoc) were localized to Chrs 1, 2, and 10 respectively, and thus provide more DNA markers for genetic mapping of quantitative trait loci for blood pressure on those chromosomes. Genes for alkaline phosphatase (Alp1) and cardiac AE-3 Cl-/HCO3- exchanger (Ae3) were both localized to Chr 9. Genes for glutamate dehydrogenase (Glud) and gastric H,K-ATPase beta subunit (Atp4b) were localized to Chr 16. The ornithine decarboxylase (Odc) gene and ornithine decarboxylase pseudogene (Odcp) were localized to Chrs 6 and 11 respectively.

Animals↗
PubMed1994

Determinants for intracellular sorting of cytoplasmic and nuclear intermediate filaments.

The mechanism by which nuclear and cytoplasmic filaments are sorted in vivo was studied by examining which lamin sequences are required to target an otherwise cytoplasmic IF protein, the small neurofilament subunit (NF-L), to the nuclear lamina. By swapping corresponding domains between NF-L and lamin A, nuclear envelope targeting of NF-L was shown to require the presence of the "head" domain, a 42-amino acid sequence unique to lamin rod domains, a nuclear localization signal and the CAAX motif. Replacement of the entire COOH-terminal tail of lamin A with that of NF-L had no discernible effect on nuclear localization of lamin A, provided the substituted NF-L tail contained a NLS and a CAAX motif. This chimeric protein exhibited characteristics more typical of lamin B than that of the parental lamin A. With regard to cytoplasmic assembly properties, substitution of the head domain of lamin A for that of NF-L did not substantially affect the ability of NF-L to coassemble with vimentin in the cytoplasm. In contrast, insertion of a 42-amino acid sequence unique to lamin rod domains into NF-L profoundly affected NF-L coassembly with vimentin indicating that the 42-amino acid insertion in lamins may be important for sorting lamins from cytoplasmic IF proteins.

Amino Acid Sequence↗
PubMed1994

Human GATA-3 trans-activation, DNA-binding, and nuclear localization activities are organized into distinct structural domains.

GATA-3 is a zinc finger transcription factor which is expressed in a highly restricted and strongly conserved tissue distribution pattern in vertebrate organisms, specifically, in a subset of hematopoietic cells, in cells within the central and peripheral nervous systems, in the kidney, and in placental trophoblasts. Tissue-specific cellular genes regulated by GATA-3 have been identified in T lymphocytes and the placenta, while GATA-3-regulated genes in the nervous system and kidney have not yet been defined. We prepared monoclonal antibodies with which we could dissect the biochemical and functional properties of human GATA-3. The results of these experiments show some anticipated phenotypes, for example, the definition of discrete domains required for specific DNA-binding site recognition (amino acids 303 to 348) and trans activation (amino acids 30 to 74). The signaling sequence for nuclear localization of human GATA-3 is a property conferred by sequences within and surrounding the amino finger (amino acids 249 to 311) of the protein, thereby assigning a function to this domain and thus explaining the curious observation that this zinc finger is dispensable for DNA binding by the GATA family of transcription factors.

Antibodies, Monoclonal↗
PubMed1994

Coculture of primary rat hepatocytes and nonparenchymal cells permits expression of insulin-like growth factor binding protein-3 in vitro.

In biological fluids, the insulin-like growth factors (IGFs) are associated with binding proteins (IGFBPs), which modify IGF distribution and action. Circulating IGFs are bound predominantly to IGFBP-3, of apparent hepatic origin, but regulation of IGFBP-3 has been difficult to dissect because of the lack of systems suitable for examining hepatic production of IGFBP-3 in vitro. In the present studies, IGFBP-3 expression was identified primarily in hepatic nonparenchymal cells, particularly Kupffer and sinusoidal endothelial cells. Coculture with hepatocytes enhanced the stability of nonparenchymal cells to express IGFBP-3 in vitro. IGFBP-3 in conditioned medium had apparent mol wt of 150-300 kilodaltons, suggesting formation of a ternary complex with IGFs and the acid-labile subunit. Expression and secretion of IGFBP-3 were hormonally responsive and strongly correlated (r = 0.79; P < 0.001), with 2- to 3-fold stimulation by added insulin or IGF-I (both P < 0.05), but not by added GH alone. Our findings suggest that GH may act indirectly to promote IGFBP-3 generation in vivo via increasing both the secretion of insulin and the hepatic production of IGF-I; in patients with diabetes mellitus, reduced circulating levels of IGFBP-3 despite high levels of GH may result from both insulin deficiency and inadequate hepatic production of IGF-I. Coculture of hepatic nonparenchymal and parenchymal cells should be useful for further analysis of the mechanism of IGFBP-3 regulation.

Animals↗
PubMed1994

[A study on Mechanism of prevention and treatment of gastric ulcer with Os sepiella in rats].

The Os Sepiella maiudrone (OSM) could markedly inhibit the stress-induced gastric mucosal lesions and promote the healing of acetic acid-induced gastric ulcer in rats were reported previously. In order to demonstrate its mechanism, the effects of OSM on acidity of gastric juice, combined mucus content in gastric wall, DNA synthesis, gastric movements, the gastric contents of prostaglandin E2 (PGE2) and cAMP of gastric tissue were examined. The results showed that OSM could neutralize the gastric acid, promote the production of cAMP and PGE2 in gastric tissue. These suggested that the neutralization of gastric acid and enhancing the gastric mucosal cytoprotection by OSM would play a role in preventing and curing gastric ulcers in rats.

Animals↗
PubMed1993

Drosophila Rrp1 complements E. coli xth nfo mutants: protection against both oxidative and alkylation-induced DNA damage.

Drosophila Rrp1 protein has four tightly associated enzymatic activities: DNA strand transfer, ssDNA renaturation, dsDNA 3'-exonuclease and apurinic/apyrimidinic (AP) endonuclease. The carboxy-terminal region of Rrp1 is homologous to Escherichia coli exonuclease III and several eukaryotic AP endonucleases. All members of this protein family cleave abasic sites. Rrp1 protein was expressed under the control of the E. coli RNA polymerase tac promoter (pRrp1-tac) in two repair deficient E. coli strains (BW528 and LG101) lacking both exonuclease III (xth) and endonuclease IV (nfo). Rrp1 confers resistance to killing by oxidative, antitumor and alkylating agents that damage DNA (hydrogen peroxide, t-butylhydroperoxide, bleomycin, methyl methanesulfonate, and mitomycin C). Complementation of the repair deficiency by Rrp1 provides up to a two log increase in survival and requires the C-terminal nuclease region of Rrp1, but not its N-terminal region. The AP endonuclease activity in extracts from the repair deficient strain LG101 is increased up to 12-fold when the strain contains pRrp1-tac. These results indicate that pRrp1-tac directs the synthesis of active enzyme, and that the nuclease activities of Rrp1 are likely to be the cause of the increased resistance to DNA damage of the mutant cells.

Alkylation↗
PubMed1993

Erythroid transcription factor GATA-1 is abundantly transcribed in mouse testis.

The transcription factor GATA-1 is a fundamental regulator of genes in haematopoietic cell lineages and belongs to a family of factors that bind to the consensus sequence WGATAR. The GATA motif was originally identified in cis-regulatory regions of globin and other erythroid-specific genes, but the range of genes controlled by the GATA factors has since expanded. Members of the GATA transcription factor family share a conserved zinc-finger DNA-binding domain, but the expression profile of each GATA factor is distinct. Here we show that a testis form of murine (m)GATA-1 messenger RNA is transcribed from a promoter located 5' to the erythroid first exon, and the remaining exons (which encode the mGATA-1 protein) are used in common by both testis and erythroid transcripts. We use an anti-mGATA-1 monoclonal antibody to show that the factor expressed in erythroid cells is the same as that found in the seminiferous tubules of murine testis. The GATA-1-expressing cells in 10-week-old testis were found only in contact with the basement membrane of seminiferous tubules, suggesting that GATA-1 regulates genes during the earliest stages of spermatogenesis.

Aging↗
PubMed1993

Treatment of acute experimental toxoplasmosis with investigational poloxamers.

Because of the limited chemotherapeutic approaches available to treat reactivated latent Toxoplasma gondii infection manifested as toxoplasmic encephalitis in AIDS patients, investigation of novel chemotherapeutic agents is warranted. Several poloxamers (nonionic block copolymers composed of a central hydrophobic chain of polyoxypropylene flanked by two hydrophilic chains of polyoxyethylene) were tested for their abilities to alter the course of acute infection with a highly virulent T. gondii in mice. The effect varied markedly with the length of the constituent chains of the copolymers. The most effective preparations were highly effective when administered after infection and afforded remarkable protection against 10 to 1,000 100% lethal doses of T. gondii. Protection was dose dependent, and multiple treatments were more effective than single treatment. These preliminary findings warrant additional studies to determine whether this novel form of antitoxoplasma chemotherapy may prove promising in the treatment or prevention of acute toxoplasmic encephalitis in humans.

Acute Disease↗
PubMed1993

[Spiral shaped bacteria in the human gastric biopsy].

Biopsy specimens from the gastric mucosa of 149 patients who underwent gastroduodenal endoscopy for upper gastrointestinal complaints were studied by light microscopy and culture. Spiral shaped bacteria were detected in four of the specimens by smears with Gram stain. The positive rate was 2.68%, but these bacteria and HP did not grow in culture. The characteristic helical morphology of the bacteria appears to be similar to that of the bacteria found in the stomach of cats and dogs. And what of significance in these cases is the presence of spiral shaped bacteria in association with chronic gastritis.

Adult↗
PubMed1992

Functional analysis of the human platelet-derived growth factor A-chain promoter region.

The platelet-derived growth factor (PDGF) A-chain gene is a developmentally regulated gene that is expressed in high levels in a limited number of normal and transformed cell lines and in cells stimulated by cytokines, including PDGF itself. We have now analyzed potential regulatory elements in 3.6 kilobase pairs (kb) of the 5'-flanking sequences of the human PDGF A-chain gene using reporter gene constructs and transient transfection analyses. The region between base pairs (bp) -618 and +392 (relative to the transcription initiation site) is sufficient for optimal promoter activity. A highly G + C region containing three contiguous Sp1 binding sites between bp -150 and -33 contributes over 80% of promotor activity. DNase I footprinting analyses indicates that Sp1 binds to and protects over 57 bp of this G + C region. A functional serum response element is located within bp -477 and -468 and positively regulates induction of PDGF A by PDGF. A negative regulatory (silencer) element is located from -1.9 to -0.9 kb. The results suggest that the major constitutive expression of the PDGF A-chain gene requires a highly G + C-rich region containing three Sp1 binding sites and that induction of the PDGF A-chain gene by PDGF is mediated by a SRE located at bp -477 to -468.

Base Sequence↗
PubMed1992

Interleukin-4 is an autocrine growth factor secreted by the L-428 Reed-Sternberg cell.

Recent evidence indicates that Reed-Sternberg (RS) cells from many cases of Hodgkin's disease have features of activated lymphocytes and that lymphokines from activated lymphocytes induce proliferation of L-428 RS cells. It is shown here that a lymphokine similar to a lymphokine secreted by activated lymphocytes is secreted by L-428 cells. This lymphokine has a molecular weight approximately equal to 68,000 daltons, identical to glycosylated recombinant interleukin-4 (rIL-4), and cross-reacts with monoclonal anti-IL-4 in Western immunoblotting. This Hodgkin's cell growth factor (HCGF) is 100% neutralized by polyclonal anti-IL-4 antibodies and competes for the IL-4 receptor. After acid-elution, the L-428 RS cell has been shown to have 3,396 +/- 120 high-affinity receptor sites/cell. HCGF competes with rIL-4 for this receptor and L-428 cells contain mRNA for IL-4. Although all evidence indicates that IL-4 is an important secreted autocrine growth factor for L-428 RS cells, anti-IL-4 has no effect on the sustained serum-free growth of these Hodgkin's cells, suggesting that either the IL-4 receptor and the IL-4 receptor-growth factor complex are protected from antibody inhibition or other mechanisms are responsible for the sustained proliferation of L-428 RS cells.

Antibodies↗
PubMed1992

Biotransformation of caffeine, paraxanthine, theobromine and theophylline by cDNA-expressed human CYP1A2 and CYP2E1.

Six human cytochrome P450s expressed in HepG2 cells using vaccinia virus cDNA-directed expression, were used to study the biotransformation of caffeine and its metabolites. CYP1A2 alone was responsible for caffeine 3-demethylation and paraxanthine 7-demethylation; in addition, 1A2 catalysed virtually all reactions related to caffeine and its metabolites. The metabolic profile of caffeine biotransformation by CYP1A2 averaged 81.5% for paraxanthine, 10.8% for theobromine and 5.4% for theophylline formation. It remained quite uniform when caffeine concentrations were varied. The most striking finding was that CYP2E1 (the ethanol-inducible form) had major influences upon caffeine metabolism: in particular, it catalysed the formation of theophylline and theobromine from caffeine. Thus, the in vivo metabolite profiling of caffeine may reveal CYP2E1 activities in addition to the previously documented activities of CYP1A2, polymorphic N-acetyltransferase and xanthine oxidase.

Biotransformation↗
PubMed1991

Reactive hyperemia in term neonates and adults--a laser Doppler fluxmetry study of skin microcirculation.

The reactivities of neonatal and adult microcirculation have been studied and compared. The cutaneous reactive hyperemia after 1 and 4 min of arterial occlusion (AO) was measured with a laser-Doppler fluxmeter in 21 healthy neonates and 10 adults. Local skin temperature, mean arterial blood pressure (MAP), and skin prick hematocrit were also determined at the same time. The magnitude of neonatal reactive hyperemia was approximately one-third that of the adult response regardless of the duration of AO. In both groups, with age-specific regressions, the hyperemic blood flow response after 4 min of AO developed more slowly in subjects with low MAP and was of low magnitude in subjects with high hematocrit values. In response to a prolongation of AO, from 1 to 4 min, the magnitude and duration of hyperemia increased significantly and similarly in both neonates and adults. We conclude that compared to adults neonates have a less pronounced ability to increase skin microcirculation in response to local ischemia. The normally low blood pressure and high hematocrit in newborn infants contribute further to this conclusion.

Adult↗
PubMed1991

Inhibition of succinate-ubiquinone reductase by nitrosalicyl-N-alkylamides.

The abilities of eight nitrosalicyl-N-alkylamides to inhibit succinate-ubiquinone reductase were compared. These compounds possess both a nitro group at 3- or 5-position of the benzyl ring, and a methyl, decyl, dodecyl or tetradecyl group subsituted for the amide hydrogen of salicylamide. The result shows the following: (a) 3-Nitrosalicyl-N-alkylamides are stronger inhibitors than 5-nitrosalicyl-N-alkylamides when they have the same alkyl group. (b) The inhibitory abilities of both 3-and 5-nitrosalicyl-N-alkylamides increase with increasing alkyl group length. (c) Kinetic data show that the inhibition by 3-nitrosalicyl-N-tetradecylamide is noncompetitive with respect to the electron acceptor Q2.

Animals↗
PubMed1991

Physicochemical characterization of recombinant human nerve growth factor produced in insect cells with a baculovirus vector.

Recombinant human nerve growth factor (rhNGF) secreted by insect cells was purified by ion-exchange and reversed-phase chromatography to near homogeneity. The N-terminus of the secreted molecule was analogous to that of mouse salivary gland NGF. In its native conformation, the insect cell produced rhNGF molecules were homodimers consisting of 120 amino acid polypeptide chains. Mature rhNGF was found not to be significantly glycosylated (less than 0.08 mol of N-acetylglucosamine/mol of protein). The rhNGF was homogeneous with regard to molecular weight and amino acid sequence. Isoelectric focusing resolved the rhNGF into one major and one minor component. Because rhNGF from insect cells can be obtained in large quantities, purified to near homogeneity, and is similar to natural NGF with regard to physicochemical properties and biological activity, it is suitable for further evaluation in animal models as a therapeutic molecule for neurodegenerative diseases such as Alzheimer's disease.

Amino Acid Sequence↗
PubMed1990

Bioavailability improvement of mycophenolic acid through amino ester derivatization.

The potential bioavailability improvement of mycophenolic acid (MPA), 1, through ester derivatization was evaluated in monkeys at a dose of 20 mg/kg in this study. The acetyl solketal ester 3 was found to have excellent partition properties but poor aqueous solubility. Thus, even though it can be converted rapidly to MPA by plasma and liver enzymes, it showed poor oral bioavailability (56% of MPA) in monkeys. The bioavailability of the morpholinoethyl ester 4 and the acetyl morpholinoethyl ester 5, on the other hand, was found to be 236 and 150% that of MPA, respectively. Since ester 5 has greater aqueous solubility, but similar chemical stability and enzymatic hydrolysis rates compared to ester 4, the better bioavailability of ester 4 may result from its greater partitioning into the gastrointestinal membranes.

Administration, Oral↗
PubMed1990

High-performance liquid chromatographic (HPLC) and HPLC-mass spectrometric (MS) analysis of the degradation of the luteinizing hormone-releasing hormone (LH-RH) antagonist RS-26306 in aqueous solution.

The kinetics of the degradation of an LH-RH antagonist, RS-26306,1, in aqueous solution from pH 1 to pH 11 were studied by reverse-phase HPLC. The pH-rate profiles at 50, 60, and 80 degrees C were U-shaped with the rate law of kobs = kHaH + kw + kOHaOH. The predicted 25 degrees C shelf life at the pH of maximum stability, pH approximately 5, is greater than 10 years. The products from the degradation were analyzed by HPLC-MS using thermospray ionization. Below pH 3, the primary product, 2, forms from the acid-catalyzed deamidation of the C-terminal amide. Above pH 7, epimerization of the individual amino acids is the principal reaction. Between pH 4 and pH 6, intramolecular serine-catalyzed peptide hydrolysis becomes important, yielding a tripeptide, 3, and a heptapeptide, 4. At the pH of maximum stability all three pathways for degradation are observed.

Chemical Phenomena↗