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Biomedical subjects

J Gui

Publications and source records attributed to J Gui.

13 recordsLinked to original sources

Threshold gradient descent method for censored data regression with applications in pharmacogenomics.

An important area of research in pharmacogenomics is to relate high-dimensional genetic or genomic data to various clinical phenotypes of patients. Due to large variability in time to certain clinical event among patients, studying possibly censored survival phenotypes can be more informative than treating the phenotypes as categorical variables. In this paper, we develop a threshold gradient descent (TGD) method for the Cox model to select genes that are relevant to patients' survival and to build a predictive model for the risk of a future patient. The computational difficulty associated with the estimation in the high-dimensional and low-sample size settings can be efficiently solved by the gradient descent iterations. Results from application to real data set on predicting survival after chemotherapy for patients with diffuse large B-cell lymphoma demonstrate that the proposed method can be used for identifying important genes that are related to time to death due to cancer and for building a parsimonious model for predicting the survival of future patients. The TGD based Cox regression gives better predictive performance than the L2 penalized regression and can select more relevant genes than the L1 penalized regression.

Algorithms↗

Orientation relationships of martensite variants determined by electron backscatter diffraction

Orientation relationships between the parent phase and 2H type martensite, and between different variants in a plate group of martensite in the CuAlNi shape memory alloy were determined by electron backscatter diffraction. The result reveals clearly that the basal planes of different correspondence variants of the 2H martensite originate from different 110P planes of the parent phase, and the [010]2H axis of each correspondence variant originates from one of the <001>P axes of the parent phase. Our result reveals also the typical relationships of four habit-variants A, B, C and D in a martensite plate group, and that the habit-variants A and C (and equivalenty B and D) are twin-related by an 1212H mirror plane, and the habit-variants A and D (and B and C) are twin-related by an 1012H mirror plane. Usually, variants A and C (and B and D) form spear morphology and variants A and D (and B and C) form fork morphology.

Journal Article↗

Monte Carlo simulations of liquid spreading on a solid surface: effect of end-group functionality.

The spreading of liquid droplets composed of molecules with or without reactive end groups over a solid surface has been studied using Monte Carlo simulations. For molecules without reactive end groups, a molecular layering in the spreading profiles is predicted, depending on the ratio of the magnitude of intermolecular interactions to thermal energy. As intermolecular interactions become smaller than thermal energy, the layered structure vanishes. For molecules with reactive end groups, interactions between end groups and between end groups and the surface complicate the situation. By assuming an end-to-end interaction between molecules and the pinning of end groups to the surface, a complex layered structure is obtained. Our simulation predicts spreading profiles that accurately describe the broad spectrum of data obtained from scanning microellipsometry for perfluoropolyalkylethers with and without reactive end groups.

Journal Article↗

Effects of dizocilpine (MK-801) on motor activity and memory.

The effects of MK-801 upon motor activity and memory were assessed in a novel use of open-field behavior testing. In this study, rats were treated with different doses of MK-801 (0.025, 0.05, 0.1 and 0.2 mg/kg) and given a brief 10-min exposure to an open-field in which locomotor activity and within-session habituation were measured. Doses of MK-801 < or =0.1 mg/kg had no effect upon locomotor activity or within-session habituation. MK-801 0.2 mg/kg produced a marked hyperlocomotion and completely prevented within-session habituation. One day later, the animals were tested for their retention of habituation to evaluate the effects of MK-801 on memory processes. In that animals treated with 0.2 mg/kg MK-801 failed to habituate to the novel environment under the influence of 0.2 mg/kg MK-801, it was not surprising that these animals were impaired on the retention test for the novel environment. Importantly, however, the 0.1 mg/kg MK-801 treatment, which did not affect locomotor activity or within-session habitation to the novel environment, severely interfered with retention of the novel environment. Additional experiments indicated that this result could not be accounted for by drug conditioning or drug state-dependent effects. Thus, the results indicated that MK-801 can produce profound effects upon motor activity and memory and that these two effects can be disassociated.

Animals↗

Cocaine sensitization can accelerate the onset of peak cocaine behavioral effects.

The development of sensitization to the behavioral effects of cocaine occurs with repeated intermittent usage. In the present study rats were given five daily i.p. injections of cocaine (10 mg/kg) immediately prior to placement in an open-field environment for 20 min to induce cocaine sensitization. Control groups received saline injections or cocaine injections (10 mg/kg) 30 min after testing in the home cage. One week later the animals were given a challenge test with 10 mg/kg cocaine. The animals that had received cocaine in the test environment exhibited a more rapid onset of cocaine-induced behavioral effects than either animals previously treated with saline or animals that had received cocaine in the home cage. In a second experiment, the same sensitization protocol was followed except that during the interval between the end of the cocaine/saline treatments and the challenge test, the animals were given six daily 20-min saline tests to assess the contribution of differential habituation and/or Pavlovian conditioning to the sensitization effect. Neither habituation or Pavlovian conditioning altered the more rapid onset of cocaine stimulant effects induced by repeated cocaine treatments. It is suggested that the faster onset of cocaine effects is another way in which cocaine sensitization contributes to cocaine abuse liability.

Analysis of Variance↗

Cocaine conditioning and cocaine sensitization: what is the relationship?

With repeated cocaine use, cocaine conditioned behavior develops to associated stimuli, and in addition, sensitization can occur to the unconditioned stimulant effects of cocaine. To investigate the relationship between the conditioned and unconditioned behavioral effects of repeated cocaine use, two groups of rats (n = 7) were given five daily paired cocaine treatments (10 mg/kg i.p.) immediately before a 20-min placement in an open-field environment. Other groups received either saline before testing or cocaine unpaired which was administered 30 min after testing in the homecage. When tested in the open-field with saline for conditioned effects, the two cocaine paired groups selectively exhibited substantial and equivalent cocaine conditioned responses. One of these groups was subjected to an extinction procedure which was effective in eliminating the cocaine conditioned responses. Subsequently, all the rats which had received cocaine in the first phase of the experiment, paired and unpaired, along with a subset of saline animals were given a cocaine (10 mg/kg i.p.) challenge test. The paired cocaine animals exhibited an earlier onset of the cocaine induced behavioral response (sensitization) as compared with the saline and the unpaired cocaine animals. Critically, the sensitization effects were unaffected by extinction, and in addition, the conditioned response did not contribute to the sensitization effect. It is suggested that the cocaine drug response occludes the cocaine conditioned response. Subsequent to this sensitization test, the animals were retested for conditioning. In this test, the paired cocaine animals which had not been subjected to the extinction procedure still exhibited a conditioned cocaine response, whereas, the paired cocaine group subjected to extinction was indistinguishable from saline controls. Although the present results show that Pavlovian conditioned responses to exteroceptive contextual cues do not directly contribute to cocaine induced behavioral sensitization effects, the sensitization effects were context-specific, and therefore, were tied to associative processes. It is suggested that context specificity is mediated by a compound stimulus complex comprised of exteroceptive stimuli and interoceptive cocaine drug cues. Furthermore, these exteroceptive and interoceptive cues associated with cocaine effectively expedite the onset of cocaine effects, and thereby, facilitate the addictive potency of cocaine.

Animals↗

A simple and reliable method for the positive identification of pavlovian conditioned cocaine effects in open-field behavior.

The identification of the Pavlovian conditioning of the behavioral effects of cocaine using open-field behavior is often confounded by the concurrent occurrence of behavioral habituation in control animals. Thus, differences in spontaneous activity between cocaine conditioned animals vs. control can be explained either by Pavlovian conditioning of the psychostimulant effects of cocaine or by anti-habituation effects of cocaine. In a series of experiments we demonstrate that location of the animal within the open-field permits a positive identification of cocaine conditioning independent from habituation factors. In three separate experiments, five daily paired 10 mg/kg cocaine treatments induced both increased locomotion as well as increased entries into the central zone in the open-field as compared with saline and cocaine unpaired control groups. Critically, in three experimental replications, animals which received the paired cocaine treatment exhibited statistically significant increases in central zone entries in non-drug tests for conditioning both with respect to the saline and cocaine unpaired groups as well as to pre-conditioning levels. In contrast, the spontaneous locomotor behavior in the cocaine paired group on the conditioning test did not reliably increase above pre-conditioning levels but rather was only increased when compared with the reduced habituated activity levels in the saline and cocaine unpaired groups. The conditioned increase in central zone entries induced by cocaine was equally robust at 4 and 9 days post-conditioning but yet could be extinguished with repeated non-cocaine exposures to the open-field environment.

Animals↗

[Senility-preventing effect of erlingcankang decoction].

Experiments with Erlingcankang Decoction showed that when given to silk worms it could noticeably prolong the growth period of larvae and raise an average of 10-day survival of the male moths; when given to mice it could prolong their life; and when given to on old rats it could markedly raise the contents of SOD in the liver and red cells, lower the content of MAO-B in the brain, LF in the brain and adrenal gland and also LPO in the liver.

Aging↗

Selection of a peptide with affinity for the tumor-associated TAG72 antigen from a phage-displayed library.

A hexapeptide phage library was used to select peptides with affinity for the tumor-associated TAG72 antigen. Twenty-one phage clones were selected after the third round of biopanning. Three phage clones with the same DNA insert of ARTLRF were found to bind more strongly to the TAG72 antigen than other phage clones and the wild-type phage. A synthetic decapeptide GAARTLRFGA with two conjunctive amino acid residues of the phage coat protein III on each side of the selected peptide was found to bind more strongly to the TAG72 antigen than to other antigens such as the mouse metallothionein. Furthermore, immunohistochemical studies revealed that this peptide displayed preferential binding to colonic adenocarcinomatous cells expressing the TAG72 antigen. Therefore, this anti-TAG72 peptide may be useful in serving as the starting point with regard to further designing peptidomimetics as potential pharmaceuticals.

Adenocarcinoma↗

Identification of a decapeptide with the binding reactivity for tumor-associated TAG72 antigen from a phage displayed library.

Peptide ligands for tumor-associated TAG72 antigen were identified by screening a large, diverse decapeptide library expressed on the surface of filamentous phages. Fifty-eight clones of phages were selected from the eluates after the third round of biopanning and their DNA inserts were sequenced. A dominant decapeptide HYVSIELPDH (14/58) was found with the binding reactivity for TAG72 antigen in the TAG72-binding ELISA and Western dot blotting. It also showed a preferential binding to colonic adenocarcinomatous cells expressing the TAG72 antigen in the histochemical study. Therefore, this anti-TAG72 decapeptide may be useful in serving as the starting point with regard to further designing peptidomimetics for potential pharmaceuticals.

Adenocarcinoma↗

[Clinical and experimental researches in the inhibition of bile pigment lithogenesis by acupuncture and moxibustion].

Clinical subjects were the patients in whom cholecystectomy and choledochotomy were performed with T tube drainage. Four groups of acupoints were established according to different point prescriptions. Under the strict control of experimental conditions and fixation of electrical acupuncture stimulation parameters, the changes of hepatic bile output were observed in five different stages before, during and after acupuncture, and compared with those in control group not treated by acupuncture. The results showed that electrical acupuncture of Ganshu (Back-Shu point) (GB 18) and Qimen (Front-Mu point) (LI 14) could obviously promote the secretion of hepatic bile. The immediate effect was superior to that in other groups. In a group not treated by acupuncture, hepatic bile output gradually decreased as time went on. In animal experiment, a model of bile pigment lithogenesis was made in guinea pig. The animals were randomly divided into five groups of control, simultaneous acupuncture, simultaneous moxibustion, re-acupuncture after one week and re-acupuncture after two weeks. The results indicated that electrical acupuncture or moxibustion of relevant acupoints such as Ganshu (GB 18) and Qimen (LI 14) could really very effectively inhibit the animal lithogenesis caused by lithogenesis food. A tendency was observed towards that the earlier acupuncture was performed, the better the preventive effect on lithogenesis. In the influence on lithogenesis bile, both acupuncture and moxibustion could reduce the contents of biliary total bilirubin and free bilirubin and the activity of biliary beta-glucuronidase. Acupuncture also produced an effect in lowering hepatic beta-glucuronidase but moxibustion didn't. Hepatohistological observation showed that lithogenous food could also cause fatty degeneration of liver, and moxibustion could markedly inhibit its progress. Both acupuncture and moxibustion didn't remarkably influence the content of serum cholesterol.

Animals↗

In situ localization and chromosomal mapping of the AG1 (Dmp1) gene.

Dentinogenesis is being used as a model for understanding the biomineralization process. The odontoblasts synthesize a structural matrix comprised of Type I collagen fibrils which define the basic architecture of the tissue. The odontoblasts also synthesize and deliver a number of dentin-specific acidic macromolecules into the extracellular compartment. These acidic macromolecules may be involved in regulating the ordered deposition of hydroxyapatite crystals within the matrix. AG1 is the first tooth-specific acidic macromolecule to have been cloned and sequenced. To identify which cells of the rat incisor pulp/odontoblast complex were responsible for synthesis of AG1, in situ hybridization was used. Digoxigenin labeled sense and anti-sense AG1 riboprobes were prepared. The AG1 mRNA was found to be expressed in the mature secretory odontoblasts. Neither pulp cells nor pre-odontoblasts showed any staining with the anti-sense probes. Chromosomal localization studies placed the AG1 gene on mouse chromosome 5q21, in tight linkage with Fgf5. AG1 has been renamed Dmp1 (dentin matrix protein 1) in accordance with present chromosomal nomenclature. Mouse 5q21 corresponds to the 4q21 locus in humans. This is the locus for the human tooth mineralization disorder dentinogenesis imperfecta Type II (DI-II). These data suggest that the Dmp1 gene is involved in mineralization and is a candidate gene for DI-II.

Animals↗

[Screening and distinguishing heavy chain variable region genes of McAb against encephalitis type B virus].

In order to prepare human-mouse chimeric antibody against encephalitis type B virus, hybridoma 51-8 cells secreting monoclonal antibody against the virus were used as material for isolating heavy-chain variable region gene of the McAb. High molecular weight DNA of the hybridoma cell was partially digested by BamHI, and then constructed a gene library containing 2 x 10(7) pfu with lambda EMBL-3 as vector. With cDNA of heavy-chain variable region of the monoclonal antibody as probe, nine positive plaques were screened from 360,000 plaques, which have been proven that they contained a fragment of heavy-chain variable region genes by dot hybridization and Southern hybridization. Four recombinants among the nine positive plaques were further distinguished with J11 probe containing J3, J4 and heavy-chain enhancer. After cutting by EcoR1, there was a 3.8 kb fragment in three recombinants as similar to that in liver cell and Sp2/0 cell, but not in the fourth recombinant (lambda 8a4) which contained a 4.5 kb fragment that did not present in liver cell and Sp2/0 cell. The results showed that the inserts in former 3 recombinants were non-rearranged fragment of heavy-chain variable region genes, but the insert in lambda 8a4 contained a rearranged functional variable region gene. The 4.5 kb fragment could not be hybridized with a probe containing J1 and J2, but contained VH, J3 or/and J4 and enhancer, that further proved it was a functional variable region gene. Therefore, the 4.5 kb fragment was isolated and subcloned in pUC 19, and its physical map was made.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗