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Biomedical subjects

D Guo

Publications and source records attributed to D Guo.

At least 145 records · Page 8Linked to original sources
PubMed1995

Identification of a protein with homology to hsp90 that binds the type 1 tumor necrosis factor receptor.

The yeast-based two hybrid has been used to identify a novel protein that binds to the intracellular domain of the type 1 receptor for tumor necrosis factor (TNFR-1IC). The TNF receptor-associated protein, TRAP-1, shows strong homology to members of the 90-kDa family of heat shock proteins. After in vitro transcription/translation and 35S labeling, TRAP-1 was precipitated using a fusion protein consisting of glutathione S-transferase and TNFR-1IC, showing that the two proteins directly interact. The ability of deletion mutants of TNFR-1 to interact with TRAP-1 was tested using the two hybrid system. This showed that the amino acid sequences that mediate binding are diffusely distributed outside of the domain in the C terminus of TNFR-1IC that signals cytotoxicity. The 2.4-kilobase TRAP-1 mRNA was variably expressed in skeletal muscle, liver, heart, brain, kidney, pancreas, lung, and placenta. TRAP-1 mRNA was also detected in each of eight different transformed cell lines. Identification of TRAP-1 may be an important step toward defining how TNFR-1, which does not contain protein tyrosine kinase activity, transmits its message to signal transduction pathways.

Amino Acid Sequence↗
PubMed1995

Paranodal structural abnormalities in rat CNS myelin developing in vivo in the presence of implanted O1 hybridoma cells.

O1 hybridoma cells, which produce a monoclonal IgM antigalactocerebroside, were implanted into the spinal cords of immature and mature rats and the cords examined 5-24 days later. Study of the younger group, in which myelin was developing at the time of implantation, revealed examples of abnormal myelin sheaths in which the repeat period was markedly increased. The paranodal regions of these abnormal sheaths were superficially normal in configuration; i.e. myelin lamellae terminated one by one as 'terminal loops' that indented the axolemma and formed normal axoglial junctions displaying periodic 'transverse bands'. Neighbouring terminal loops are normally joined by tight junctions that block passage of tracers from the paranodal periaxonal space into the compact myelin, as seen after implantation of a control hybridoma. In the abnormal sheaths that developed after O1 implantation, in contrast, terminal loops were usually widely separated from each other. As a result, multiple pathways from the paranodal periaxonal space into the myelin sheath remained patent, forming potential routes for shunting nodal action currents. This subtle abnormality could thus compromise conduction, even though the sheaths might appear to be normally myelinated at the histological level. Equivalent abnormalities in human neurological diseases, including multiple sclerosis and paraproteinemic neuropathies, could underlie functional loss in the absence of frank demyelination.

Animals↗
PubMed1995

Protection by chlorophyllin and indole-3-carbinol against 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced DNA adducts and colonic aberrant crypts in the F344 rat.

The most abundant heterocyclic amine in fried ground beef, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), induces colon carcinomas in the male F344 rat. The potential chemopreventive effects of two compounds, namely, the 'interceptor molecule' chlorophyllin (CHL) and a modulator of carcinogen activation, indole-3-carbinol (I3C), were examined in a PhIP colon carcinogenesis model. During weeks 3 and 4 of a 16-week study, F344 rats were given PhIP by oral gavage (50 mg/kg body weight, alternating days). Inhibitors were given either before and during PhIP exposure, after PhIP treatment, or continuously for 16 weeks. Treatment of rats with 0.1% CHL in the drinking water inhibited the formation of aberrant crypt foci (ACF) with > or = 4 crypts/focus, from 1.4 +/- 0.9 in controls to 0.7 +/- 0.3 following post-initiation CHL treatment, and to 0.3 +/- 0.5 in rats given CHL continuously for 16 weeks (mean +/- SD; P < 0.05). Potent inhibition of PhIP-induced ACF occurred following initiation, post-initiation and continuous exposure to 0.1% I3C in the diet. Using the initiation protocol, I3C completely inhibited the induction of the ACF with > or = 4 crypts/focus. In a separate experiment, rats were given 0.1% CHL in the drinking water or 0.1% I3C in the diet for 4 weeks. At the end of week 3, animals received 50 mg PhIP/kg body weight by single oral gavage and PhIP-DNA adducts were quantified in the colon and several other tissues by 32P-postlabeling analysis. In addition, the urine and feces were collected to study the effects of inhibitor treatment on PhIP metabolism and excretion. No significant protection against PhIP-DNA adduct formation was detected in the colon after CHL dosing, nor was a consistent pattern of CHL inhibition observed in several other tissues. In contrast, I3C shifted the time-course of adducts in all tissue; compared with controls, adducts were increased by I3C at 6 h but decreased at 24 h and 7 days following PhIP treatment. Analysis of urine metabolites revealed that I3C and CHL decreased the excretion of unmetabolized PhIP and 4'-hydroxy- << PhIP but increased the phase II detoxification products PhIP-4'-O-glucuronide and PhIP-4'- sulfate. In the feces, the elimination of unmetabolized PhIP was increased from 54.5% in controls to approximately 67% in CHL-treated rats and decreased to 28% in rats given I3C (P < 0.05). These results support a protective role for CHL and I3C against PhIP-induced colon carcinogenesis through mechanisms which alter the uptake or metabolism of the carcinogen, and by suppression in the post-initiation phase.

Animals↗
PubMed1995

Prunus necrotic ringspot ilarvirus: nucleotide sequence of RNA3 and the relationship to other ilarviruses based on coat protein comparison.

The RNA3 of prunus necrotic ringspot ilarvirus (PNRSV) has been cloned and its entire sequence determined. The RNA3 consists of 1943 nucleotides (nt) and possesses two large open reading frames (ORFs) separated by an intergenic region of 74 nt. The 5' proximal ORF is 855 nt in length and codes for a protein of molecular mass 31.4 kDa which has homologies with the putative movement protein of other members of the Bromoviridae. The 3' proximal ORF of 675 nt is the cistron for the coat protein (CP) and has a predicted molecular mass of 24.9 kDa. The sequence of the 3' non-coding region (NCR) of PNRSV RNA3 showed a high degree of similarity with those of tobacco streak virus (TSV), prune dwarf virus (PDV), apple mosaic virus (ApMV) and also alfalfa mosaic virus (AIMV). In addition it contained potential stem-loop structures with interspersed AUGC motifs characteristic for ilar- and alfamoviruses. This conserved primary and secondary structure in all 3' NCRs may be responsible for the interaction with homologous and heterologous CPs and subsequent activation of genome replication. The CP gene of an ApMV isolate (ApMV-G) of 657 nt has also been cloned and sequenced. Although ApMV and PNRSV have a distant serological relationship, the deduced amino acid sequences of their CPs have an identity of only 51.8%. The N termini of PNRSV and ApMV CPs have in common a zinc-finger motif and the potential to form an amphipathic helix.

Amino Acid Sequence↗
PubMed1995

Differential regulation of angiotensin II receptor subtypes in rat kidney by low dietary sodium.

This study was designed to determine whether expression of renal messenger RNA (mRNA) encoding the two known angiotensin II type 1 (AT1) receptor subtypes (AT1A and AT1B) can be regulated by dietary sodium. Seven-week-old male Wistar rats were fed a low-sodium diet (0.07%, n = 9) or a normal-sodium diet (0.5%, n = 9 [control]) for 14 days. A rat AT1 complementary DNA (cDNA) probe, which hybridizes to mRNA encoding both the AT1A and AT1B receptor subtypes, and cDNA probes, which are selective for AT1A or AT1B mRNA, were used in Northern blot or in situ hybridization analysis. By use of Northern blot analysis, renal mRNA levels for the AT1 and AT1A receptors in rats fed a low-sodium diet were found to be increased twofold (P < .05) compared with control. Because renal AT1B mRNA content was not detected by Northern blot analysis, quantitative image analysis of in situ hybridization with a digoxigenin-labeled cRNA probe made from AT1B cDNA was used. In situ hybridization analysis indicated that AT1B mRNA was expressed in the proximal and collecting tubules of the kidney in rats fed a normal-sodium diet. The low-sodium diet significantly decreased the percent positive staining area of AT1B mRNA in the renal cortex (5.51 +/- 0.77% versus 2.73 +/- 0.35%, P < .05) and medulla (4.76 +/- 0.70% versus 2.01 +/- 0.43%, P < .05) compared with the control diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

[Determination of psoralen and isopsoralen in tincture of fructus Psoraleae by HPLC].

A reversed-phase HPLC method was described for the determination of psoralen and isopsoralen in tincture of Fructus Psoraleae. After adding the internal standard and diluting the sample to a definite volume, the sample was injected and analysed. The RSDs were within 2% and the minimum working concentrations below 1 microgram/ml; the average recoveries of psoralen and isopsoralen 102.8% and 99.5% respectively and the linear ranges of psoralen and isopsoralen 12-200 micrograms/ml and 13-210 micrograms/ml (r = 0.999) respectively.

Chromatography, High Pressure Liquid↗
PubMed1995

Enroute toward a computer based patient record: the ACIS project.

The clinical arm of the University of Utah operates a 400 bed general hospital and 30 specialty and subspecialty clinics and with the advent of managed care will soon be linked to a much wider network of health care facilities throughout the state. Each of these patient care facilities maintains its own patient record. To provide common access to data on any patient needed to provide continuity to the care process where ever it occurs, the institution has embarked on the development of a completely electronic patient record. In this paper we will describe the route we have taken to achieve this goal in hopes of providing some sign posts along the way for others seeking the same destination.

Computer Communication Networks↗
PubMed1995

Protective properties of chlorophylls against the covalent binding of heterocyclic amines to DNA in vitro and in vivo.

The protective properties of chlorophylls have been studied using inhibition of carcinogen-DNA binding as an end point. Rats were co-administered sodium/copper chlorophyllin (CHL) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) by single oral gavage. Eight hours after dosing, CHL inhibited IQ-DNA binding in liver by approximately 60% compared with rats given IQ alone. CHL treatment reduced the total radiolabel eliminated in urine and bile but caused increased excretion via the feces, including enhanced elimination of unmetabolized IQ. In a second study, CHL produced dose-related inhibition of IQ-DNA binding in the liver, large intestine and small intestine, and blocked IQ absorption from ligated sections of the intestine in situ. In in vitro studies CHL competitively inhibited microsome-mediated IQ-DNA binding, and interacted with liver microsomes to produce a difference spectrum with a peak at approximately 420 nm and a trough at 383 nm. CHL also interacted directly with heterocyclic amines to form 2:1 (IQ-type) or 1:1 complexes (non-IQ-type) with dissociation constants in the range 0.333 to 0.083 mM. Finally, in hepatocytes chlorophyll a inhibited the metabolism of 3-amino-1-methyl-5H-pyrido [4,3-b]indole (Trp-P-2) and produced dose-related inhibition of Trp-P-2-DNA binding. Collectively, these studies suggest that chlorophylls operate as interceptor molecules and limit carcinogen bioavailability. As a contributing mechanism, chlorophylls may interfere with cytochrome P450-mediated activation of chemical carcinogens.

Administration, Oral↗
PubMed1994

Mechanisms of the in vitro antimutagenic action of chlorophyllin against benzo[a]pyrene: studies of enzyme inhibition, molecular complex formation and degradation of the ultimate carcinogen.

Mechanisms of the antimutagenic action of chlorophyllin (CHL) towards benzo[a]pyrene (BP) were studied in vitro. In the Salmonella assay, CHL inhibited the mutagenic activity of BP in the presence of an S9 activation system and was particularly effective against the direct-acting ultimate carcinogen, benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE). Spectral studies indicated that the time-dependent hydrolysis of BPDE to tetrols was augmented in the presence of CHL concentrations on the order of 5 microM. Dose-related inhibition of several cytochrome P450-dependent enzyme activities was observed upon addition of CHL to in vitro incubations. Spectral changes for the interaction between CHL and cytochrome P450 indicated that CHL does not bind to the active site of the enzyme, but exerts its inhibitory effect indirectly. This was achieved by inhibiting NADPH-cytochrome P450 reductase (Ki approximately 120 microM with cytochrome c as substrate), and did not involve lowering of the effective substrate concentration by complex formation with the procarcinogen. It is concluded that the in vitro antimutagenic activity of CHL towards BP involves accelerated degradation of the ultimate carcinogen, with inhibition of carcinogen activation occurring only at high CHL concentrations. The latter mechanism is unlikely to occur in vivo following p.o. administration due to the limited uptake of CHL from the gut, but tissue concentrations may be sufficiently high to cause degradation of BPDE.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1994

Effects of cerebellar lesions on tonic seizures, tremor and lifespan in myelin-deficient rats.

In common with other dysmyelinating mutants, the myelin-deficient rat displays an action tremor and tonic seizures culminating in the death of the animals at approximately 23-26 days. We find that deep lesions of the cerebellar vermis alleviate the manifestations of the myelin deficiency significantly. Such lesions introduced at 20 days or later eliminate both tremor and seizures for periods up to 10 days. Lifespan is prolonged to nearly 30 days, on average, and to 35 days in some cases. Shallow lesions of the vermis or lateral lobe lesions have relatively little effect. Based on these observations we suggest that the cerebellum contributes not only to the action tremor but also to the tonic seizures characteristic of central myelin deficiency. Spontaneous activity originating in myelin-deficient fiber tracts may be carried to the cerebellum and processed there to produce a highly amplified and/or synchronized output to broad areas of the neuraxis. Deep lesions of the vermis presumably interfere with cerebellar output and compromise the cerebellar contribution to the seizures. Tonic seizures and other 'paroxysmal attacks' also occur commonly in human demyelinating diseases including multiple sclerosis [11]. Manipulation of cerebellar output offers a potential approach to the control of such spontaneous activity.

Animals↗
PubMed1994

Inhibition of CNS myelin development in vivo by implantation of anti-GalC hybridoma cells.

Implantation of hybridoma cells that secrete a monoclonal antigalactocerebroside into the dorsal columns of < or = 9-day-old rat spinal cord results in failure of development of dorsal column myelin in the vicinity of the implant. Clusters of apparently undamaged amyelinated axons remain among the hybridoma cells. Ventral myelin is unaffected. These in vivo results support antibody-mediated inhibition of myelin formation as a potential mechanism underlying failure of remyelination in multiple sclerosis.

Animals↗
PubMed1994

Inhibition of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-DNA binding in rats given chlorophyllin: dose-response and time-course studies in the liver and colon.

Chlorophyllin (CHL), a water-soluble salt of chlorophyll, has been shown to inhibit 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-DNA binding in vitro by a mechanism that involves molecular complex formation with the carcinogen. Based on this mechanism, rats weighing approximately 160 g were given 10 mumol (100 microCi) IQ or IQ plus 20, 200 or 1000 mumol CHL by single oral gavage. Six hours after dosing, CHL produced dose-related inhibition of IQ-DNA binding in three target organs for carcinogenesis, namely, the small intestine, large intestine and liver. In the latter tissues, > 80% inhibition was detected at the highest CHL dose tested, while IQ-DNA binding levels in the small intestine were reduced to below the limit of detection. Co-injection of CHL and IQ into ligated sections of small intestine inhibited the absorption of IQ in a dose-related manner, such that the highest dose of CHL almost completely blocked carcinogen uptake. Finally, rats given CHL by gavage at time 0 h were treated with IQ at various times thereafter and IQ-DNA binding levels were measured in the liver and colon 6 h after carcinogen exposure. Compared with controls given IQ alone, CHL inhibited binding by 79% at 0 h and 40% at 1 h in the liver, and by 63% at 0 h, 38% at 1 h and 58% at 24 h in the colon (P < 0.05 by Student's t-test). These results support a mechanism involving complex formation between CHL and IQ in vivo and suggest that the inhibitor is likely to be most effective when ingested simultaneously with the carcinogen.

Animals↗
PubMed1993

Antimutagenic potency of chlorophyllin in the Salmonella assay and its correlation with binding constants of mutagen-inhibitor complexes.

Chlorophyllin (CHL) is a water-soluble salt of chlorophyll that exhibits antimutagenic activity in short-term genotoxicity assays and inhibits carcinogen-DNA binding in vivo. The antimutagenic potency of CHL was studied against several structurally related heterocyclic amines using the Salmonella assay. The mutagens included 2-amino-3-methylimidazo[4,5,-f]-quinoline (IQ) and seven related IQ-type compounds, and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) and three additional non-IQ-type compounds. No relationship was observed between mutagenic potency (revertants/ng mutagen) and antimutagenic potency when expressed in terms of the CHL dose/plate-inhibiting mutagenicity by 50 percent (I50). However, a correlation was observed between mutagenic potency and the mole ratio of CHL to mutagen giving 50% inhibition (MR50), with most mutagens requiring several hundredfold to several thousandfold molar excess of CHL for inhibition. In spectrophotometric studies, CHL formed noncovalent molecular complexes with the heterocyclic amines, with binding constants in the range 3-13 x 10(3) M-1. Binding constants were inversely correlated with I50 and MR50 values, i.e., with increasing strength of complex formation less CHL/plate and a lower mole ratio of CHL to mutagen was required to inhibit mutagenicity. The results support an inhibitory mechanism in which chlorophylls operate as "interceptor molecules," interacting with carcinogens and mutagens directly and limiting their bioavailability.

Amines↗
PubMed1993

Myelin formation by mouse glia in myelin-deficient rats treated with cyclosporine.

Previous attempts to generate myelin in the myelin-deficient rat spinal cord by transplanting mouse glia were not successful. In order to determine whether this result was due to graft rejection or to interspecies mismatch of cellular or molecular components at the axoglial junction, we have repeated the experiment in cyclosporine-treated rats. Our results show that in the immunosuppressed hosts, foetal glial xenografts form an abundance of myelin within the dorsal columns at or near the injection site about two weeks after the operation. In some cases, myelination extends virtually across the entire width of the dorsal columns. Ultrastructurally, the myelin sheaths are normal in all respects, including the presence of the 'radial component'. The lateral edges of the myelin lamellae form typical paranodal axoglial junctions, some displaying periodic 'transverse bands'. We infer that previous mouse to rat xenograft failures reflect host immune response rather than mismatch of heterologous junctional components. We also compared foetal, early post-natal and adult xenografts. Foetal donor cells, containing an abundance of precursors but virtually no mature oligodendrocytes, are more effective than neonatal donor cells in forming myelin, and after adult grafts, we found no myelin formation. Thus, in xenografts, as in allografts, foetal precursor cells are far more suitable than glia from mature donors in generating significant amounts of myelin.

Animals↗
PubMed1993

[An investigation of medicinal Rhodiola in Sichuan Province].

Twenty-two species of Rhodiola produced in Sichuan Province are reported in this paper, including their distributions, habitats and localities. Among them, there is a new species named Rhodiola wolongensis. Its morphology has been described in Latin. I key for the identification of all these 22 species has been compiled and presented.

China↗
PubMed1993

DNA sequence-selective binding of head-to-tail linked bis-lexitropsins: relation of phasing to cytotoxic potency.

A series of polymethylene, -(CH2)n-tether-linked head-to-tail bislexitropsins (n = 1-7) have been synthesized in order to assess the effect on DNA binding of phasing, that arises because of lack of dimensional correspondence between oligopeptides and oligonucleotides. Binding constants to poly(dA-dT), estimated from ethidium displacement, are from 0.55 to 16.66 x 10(8) M-1. Comparable Ka values for calf thymus DNA and for poly(dG-dC) are approximately 10(6) and approximately 10(5) M-1, respectively reflecting the anticipated AT preference. Sequence-selective binding was examined by reflecting the anticipated AT preference. Sequence-selective binding was examined by methylethidium propyl ethylenediamine tetraacetic acid (MPE) complementary strand footprinting on an EcoRI/HindIII restriction fragment of pBR322 DNA with r = 0.08 and 0.32. Ligands bearing N-methylpyrrole dipeptide moieties linked by -(CH2)n, where n = 2, 4 or 6, give evidence of bidentate binding in (AT)n-rich sequences from footprinting at r = 0.32. By contrast, those ligands linked by (CH2)n, where n = 1, 3, 5 or 7, bind in a predominantly monodentate fashion. Cystostatic activity against KB human nasopharyngeal cancer cells has shown enhanced potency, compared with distamycin, for those linked bis-lexitropsins with n = 2, 4 and 6. That the increased potency may be attributed to more effective DNA binding in the latter cases is indicated by the fact that the n = 1, 3, 5 and 7 ligand homologues do not exhibit comparable enhanced cytotoxic potency.

Antineoplastic Agents↗