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Biomedical subjects

L Gu

Publications and source records attributed to L Gu.

At least 37 records · Page 2Linked to original sources
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

[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

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↗
PubMed1990

Drug-excipient incompatibility studies of the dipeptide angiotensin-converting enzyme inhibitor, moexipril hydrochloride: dry powder vs wet granulation.

The drug-excipient incompatibility screen for moexipril hydrochloride (1) using various isothermal stress methods is reported herein. It was found that most of the commonly used filters, disintegrants, lubricants, glidants, and coating agents were incompatible with 1 in dry powder mixtures; moisture and basic (or alkalizing) agents were determined to be the dominant destabilizing factors. In wet granulations, basic agents, however, were found to suppress drug degradation even in the presence of moisture. Supported by the product distribution studies, the stabilization is proposed to involve the neutralization of the acidic drug by the basic excipients.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Development and characterization of a lyophilized dosage form of IL-1 beta.

The development and characterization of a lyophilized dosage form for recombinant Interleukin-1 beta is described. Included in the evaluation of the drug product are accelerated and long-term stability studies utilizing a number of biophysical techniques (reverse-phase HPLC, SDS-PAGE, isoelectric focusing and ELISA). Data collected with these methods were examined for correlations with biological activity assessments provided by an in-vitro cell culture system (mouse thymocyte proliferation). Results of these studies demonstrate that a lyophilized dosage form of Interleukin-1 beta can be prepared which retains its potency for at least 1 year when stored at ambient temperature. The analytical methodology used to assess the physicochemical integrity of the protein provided a sensitive and reproducible means of predicting changes in biological activity.

Animals↗
PubMed1989

An unexpected pH effect on the stability of moexipril lyophilized powder.

Because of the limited stability of moexipril (RS-10085; 1) in aqueous solution, lyophilized parenteral formulations were evaluated as a function of pH in this study. In general, the lyophilized powder of 1 showed about two orders of magnitude less reactivity at 50 degree C than in aqueous solution at pH values below 3 or above 6. At pH 5.1, however, the lyophilized powder had maximum reactivity, with the rate actually comparable to that observed in aqueous solution. When the distribution of the two major products, diketopiperazine (DKP) 2 and ester hydrolysis analogue 3, was compared to the observed kinetics as a function of pH, it was clear that removal of water via lyophilization suppressed the spontaneous k1 cyclization process, the spontaneous k3 hydrolysis process, and the specific base-catalyzed k4 hydrolysis process. The overall spontaneous k2 cyclization process, however, was not affected by lyophilization. The latter result is accounted for by the increased equilibrium constant for the formation of the tetrahedral intermediate, To, as a result of lyophilization. This study demonstrates that stability data in solution can not be used for predicting the stability of moexipril in lyophilized powder form.

Chromatography, High Pressure Liquid↗
PubMed1989

Studies of safe maximal daily dietary selenium intake in a seleniferous area in China. I. Selenium intake and tissue selenium levels of the inhabitants.

Studies of marginal safe Se-intake have been carried out in a seleniferous section of China since 1985. Three areas with low, medium and high Se levels were selected for this study. The respective average daily Se-intake (mean +/- SE) was 70.5 +/- 4.8 micrograms, 194.7 +/- 22.9 micrograms and 1438.2 +/- 76.3 micrograms for males, and 62.0 +/- 3.6 micrograms, 198.1 +/- 23.8 micrograms and 1238.5 +/- 64.6 micrograms for females (average body weight: male 55 Kg, female 53 Kg). When the increasing rate of Se-intake was compared with the corresponding tissue-Se levels it was found that the whole blood Se-level reflected more closely the physiological range of Se-intake, while at higher Se-intakes it became less sensitive than the levels in hair, finger-nail and toe-nail, which were comparable to the sensitivity of urine. It is suggested that hair, finger- and toe-nail may all act as excretory organs when excess amounts of Se are ingested. Hair- and blood-Cd are somewhat higher in residents of the high Se area, but whether they have influenced human Se-metabolism at the high level of Se-intake is not yet known. Significant correlations on log-log plots were obtained between levels of daily Se-intake and whole blood r = 0.878), breast milk (r = 0.899) and 24-h-urine (r = 0.859). Highly significant correlations on log-log plots between levels of tissue were also obtained: urine Se--plasma Se (r = 0.968), whole blood Se--hair Se (r = 0.952), fingernail Se--toenail Se (r = 0.919), hair Se--fingernail Se (r = 0.914), hair Se--toenail Se (r = 0.891), whole blood Se--toenail Se (r = 0.849) and whole blood Se--fingernail Se (r = 0.836). The highly significant correlations found between the Se-intake and the tissue-Se level, and also between the Se levels of various tissues, could possibly conveniently be used to convert the known tissue-Se level to the corresponding Se-intake. Taken together with the wide range of Se-intakes and corresponding tissue-Se levels this would provide the necessary conditions for studying the marginal and maximal safe Se-intakes in humans.

Arsenic↗
PubMed1989

Studies of safe maximal daily dietary Se-intake in a seleniferous area in China. Part II: Relation between Se-intake and the manifestation of clinical signs and certain biochemical alterations in blood and urine.

Selenosis occurs in areas of Enshi county because of the high Se content of the food. Morphological changes in finger-nails were used as the main criterion for clinical diagnosis of selenosis. Pathological nails were observed to occur almost only in adults, not at all in young children and very seldom in teenagers. Symptoms of selenosis in susceptible patients were found at or above an Se-intake of 910 micrograms/d, corresponding to a blood Se level of 1.05 mg/L. There was no evidence for an increased susceptibility to dental caries due to high Se consumption, and an increase in Se-intake seems unlikely to reduce the beneficial effects of fluoride on caries. No abnormalities of liver or heart were seen by supersonic B or electrocardiographic examinations. The biochemical investigations showed that with increasing whole blood Se the ratio of plasma Se to erythrocyte Se tended to decrease. As Se-intake increases to over 750 micrograms daily, the ratio decreases to near a minimal level. Reduced glutathione in whole blood decreases within a blood Se range of 1.01 to 2.28 micrograms in the high Se area. The amount of trimethylselenonium ion excreted in urine increased with the increase of urinary Se. Cases with prolonged prothrombin time occurred as blood Se increased to a level above 1 mg/L. The white blood cell count also increased significantly. Quantitative values were obtained only for ratio of plasma-Se to erythrocyte-Se for prothrombin time and for maintenance of nail Symptoms of susceptible patients. The overall results indicated that a daily Se-intake of 750-850 micrograms [corrected] might be the marginal level of safe intake. When other variable factors are also taken into consideration a daily Se-intake of 400 micrograms [corrected] is suggested as the maximum daily safe intake. At this level of Se-intake the corresponding approximate tissue Se levels are: whole blood 0.559 mg/L, plasma 0.327 mg/L, urine excretion 173 micrograms/d, hair 3.60 mg/kg, toe-nails 4.25 mg/kg, and finger-nails 4.70 mg/kg.

Anemia↗
PubMed1988

Transient opacification of the urinary pathways by amorphous debris in children with leukemia.

Our index patient, a 14-year-old male on chemotherapy for acute lymphatic leukemia had extensive opacification of the urinary tract on the preliminary film for an intravenous urogram. Sonography and computed tomography also demonstrated dense material in the calyces, renal pelves and ureters. Since then, we have found another patient, a 9-year-old female with acute lymphatic leukemia who was not receiving chemotherapy, with a similar pattern on sonography and computed tomography. These densities unlike those in our first patient were not visible on a plain film of the abdomen. All of the material disappeared spontaneously in both patients.

Adolescent↗