Biomedical subjects

J Ma

Publications and source records attributed to J Ma.

At least 199 records · Page 11Linked to original sources

PubMed2000

Use of COMPARE analysis to discover new natural product drugs: isolation of camptothecin and 9-methoxycamptothecin from a new source.

Analysis of cytotoxicity data of extracts from the National Cancer Institute's Active Repository by the COMPARE protocol was carried out using camptothecin as a reference point. Extracts identified by this process were further characterized by a selective yeast bioassay for inhibitors of topoisomerase I and by a biochemical assay for compounds that stabilize the topoisomerase I-DNA covalent binary complex. Five of the extracts were positive in the yeast bioassay, and eight extracts showed activity on the assay that monitors stabilization of the topoisomerase I-DNA complex. Four of the latter extracts were inactive in the yeast bioassay, and thus would not have been identified as hits without the COMPARE preselection process. One of the extracts, from Pyrenacantha klaineana, was selected for detailed investigation, and fractionation of this extract yielded camptothecin and 9-methoxycamptothecin as the bioactive constituents.

Algorithms↗

PubMed2000

Modulation of the basal activity of phosphatidylinositol-3-kinase/protein kinase B signaling pathway in human hepatocarcinoma cells.

The modulation of GnT-V activity by signaling molecules in PI-3-K/PKB pathway in human hepatocarcinoma cell line 7721 was studied. GnT-V activity was determined after the transfection of sense or antisense cDNA of PKB into the cells, as well as the addition of activators, specific inhibitors, and the antibodies to the enzyme assay system or culture medium. It was found that the basal activity of GnT-V was up regulated by the sense and down regulated by the antisense cDNA of PKB transfected into 7721 cells. GnT-V was activated by PIP2, PIP3 or GTPgamma[S] added to the assay system, and the activation of PIP2 or GTPgamma[S] was abolished by LY2940002, a specific inhibitor of PI-3-K, but the activation of PIP3 was not attenuated by LY2940002. In addition, GnT-V activity in cultured parental or H-ras transfected cells was inhibited by the antibody against PKB or PI-3-K. These findings demonstrated the involvement of PI-3-K/PKB signaling pathway in the regulation of GnT-V. Moreover, ET18-OCH3, an inhibitor of Raf translocation and PI-PLC enzyme, which produces the activator of PKC, as well as the antibodies against Raf-1 or MEK also inhibited GnT-V activity in the parental and H-ras transfected cells. The inhibitory rates, however, were less in the transfected cells than those in the parental cells. These results reveal that in parental and H-ras transfected 7721 cells, the basal activity of GnT-V is also regulated by the Ras/Raf-1/MEK/MAPK cascade in addition to PI-3-K/PKB signaling pathway. The significance of these two pathways in the regulation of GnT-V and their relations to the activation of PKC previously reported by our laboratory (Ju TZ et al., 1995 Glyconjugate J 12, 767-772) was discussed.

Antibodies, Monoclonal↗

PubMed2000

Steady-state kinetic analysis of human ubiquitin-activating enzyme (E1) using a fluorescently labeled ubiquitin substrate.

We report the synthesis of fluorescently labeled ubiquitin (Ub) and its use for following ubiquitin transfer to various proteins. Using Oregon green (Og) succinimidyl ester, we prepared a population of Ub mainly labeled by a single Og molecule; greater than 95% of the Og label is associated with Lys 6 of Ub. We demonstrate that Og-Ub is efficiently accepted by Ub-utilizing enzymes, such as the human ubiquitin-activating enzyme (E1). We used this fluorescent substrate to follow the steady-state kinetics of human E1-catalyzed Ub-transfer to the ubiquitin-carrier enzyme Ubc4. In this reaction, E1 uses three substrates: ATP, Ubc4, and Ub. The steady-state kinetics of Og-Ub utilization by E1 is presented. We have also used analytical ultracentrifugation methods to establish that E1 is monomeric under our assay condition (low salt) as well as under physiological condition (150 mM NaCl).

Binding, Competitive↗

PubMed2000

The multifocal electroretinogram in age-related maculopathies.

To measure and compare the multifocal electroretinogram in control group and patients with age-related maculopathies, 17 eyes of control subjects, 9 eyes of wet-form ARMD, 8 eyes of dry-form ARMD and 14 eyes of idiopathic macular hole were tested with VERIS Sciences 4.0. The latencies and average response densities of 6 ring retinal regions in control eyes were compared with those in ARMD and macular hole. The amplitude depression and latency prolongation were found in age-related maculopathies. The changes of multifocal ERG were dramatic in wet-form ARMD and moderate in dry-form ARMD and IMH, which were correspondent with the pathological changes of the diseases. Our results suggest that the multifocal electroretinogram can be used to quantity the visual function in age-related maculopathies.

Aged↗

PubMed2000

Enhancement of immunogenicity of tumor cells by cotransfection with genes encoding antisense insulin-like growth factor-1 and B7.1 molecules.

Insulin-like growth factor-1 (IGF-1) is expressed in many tumor cell lines and has a role in both normal cell proliferation and in the growth of cancers. Tumor cells transfected with a vector encoding an IGF-1 antisense cDNA transcriptional cassette driven by the mouse metallothionein-1 promoter become immunogenic and lose their tumorigenicity in syngeneic animals. The enhanced immunogenicity is associated with an up-regulation in the expression of major histocompatibility complex class I molecule on cell surfaces. Blockade of the expression of IGF-1 in tumor cells by the IGF-1 antisense RNA approach is not uniformly effective in the induction of antitumoral protective immunity in low and nonimmunogenic tumor model systems. Here, we report that the immunogenicity of hepa 1-6 hepatoma and SMCC-1 colon carcinoma cells, which are poorly immunogenic and unresponsive to antisense IGF-1 gene transfer, can be induced by cotransfection with genes encoding antisense IGF-1 and mouse B7.1 molecules. The tumor cells modified in this manner become strongly immunogenic and can be used as a cellular vaccine to induce a protective immune response in vivo. Immunization with the transfected tumor cells also results in regression of the established hepa 1-6 hepatoma and SMCC-1 colon cancer. The immunity is tumor-specific and is mediated by CD3+ CD8+ T cells. Cytotoxic T lymphocytes generated in vitro by priming naive spleen cells and in vivo by immunizing mice with the double-transfected tumor cells specifically lysed autologous tumors cells and were effective in adoptive immunotherapy. The data suggest that modification of tumor cells in vitro by cotransfection with genes encoding antisense IGF-1 and B7.1 molecules may open a new avenue for cancer immunogene therapy.

Adjuvants, Immunologic↗

PubMed2000

Thrombin is a novel regulator of hexokinase activity in mesangial cells.

BACKGROUND: Hexokinase (HK) activity is fundamentally important to cellular glucose uptake and metabolism. Phorbol esters increase both HK activity and glucose utilization in cultured mesangial cells via a protein kinase C (PKC)- and extracellular signal-regulated kinases 1 and 2 (ERK1/2)-dependent mechanism. In adult kidneys, increased HK activity has been reported in both glomerular injury and in diabetes, but the mechanisms responsible for these changes are unknown. Thrombin, a known activator of both PKC and ERK1/2, is increased in the settings of renal injury and diabetes. Thus, thrombin may contribute to the observed changes in HK activity in vivo. METHODS: Thrombin and thrombin receptor agonists were tested for the ability to increase HK activity and glucose metabolism in murine mesangial (SV40 MES 13) cells. ERK1/2 activation was also evaluated in parallel. Thrombin inhibition (hirudins), PKC depletion, Ser-Thr kinase inhibition (H-7), MEK1/2 inhibition (PD98059), pertussis toxin (PTX), and general inhibitors of transcription or translation were then tested for the ability to attenuate these effects. RESULTS: Thrombin (>/=0.01 U/mL) mimicked the effect of phorbol esters, increasing HK activity> 50% within 12 to 24 hours (P < 0.05). This effect was inhibited by hirudins, mimicked by thrombin receptor agonists, and accompanied by increased Glc utilization. H-7, PD98059, and general inhibitors of transcription or translation-but not PTX-prevented thrombin-induced HK activity at 24 hours. PKC depletion and PD98059 also blocked the associated phosphorylation and activation of ERK1/2. CONCLUSIONS: Thrombin increases mesangial cell HK activity via a PTX-insensitive mechanism involving thrombin receptor activation, PKC-dependent activation of ERK1/2, and both ongoing gene transcription and de novo protein synthesis. As such, thrombin is a novel regulator of HK activity in mesangial cells and may play a role in coupling renal injury to metabolism.

Animals↗

PubMed2000

Antioxidant intakes and smoking status: data from the continuing survey of food intakes by individuals 1994-1996.

BACKGROUND: Cigarette smoking is a major risk factor for several chronic oxidative diseases that can be ameliorated by antioxidants. OBJECTIVES: This study identified the typical dietary intakes and the major food group contributors of the antioxidants beta-carotene, vitamin C, and vitamin E by smoking status. DESIGN: The 1994-1996 Continuing Survey of Food Intakes by Individuals (CSFII) provided the current sample (n = 6749), who were categorized as non- (n = 3231), former (n = 1684), and current (n = 1834) smokers. In the CSFII, individuals' food intakes were estimated with two 24-h dietary recalls. Data were analyzed by using a chi-square test with a simultaneous Fisher's z test, analysis of variance with Scheffe's test, multivariate analysis of covariance, and analysis of covariance with Bonferroni adjustment for multiple comparisons. RESULTS: The sample consisted of 3707 men and 3042 women. Current smokers tended to be younger with less education and lower incomes than nonsmokers and former smokers. The average body mass index (in kg/m(2)) of current smokers was 25.8, the lowest of the 3 groups. Current smokers had the lowest dietary antioxidant intake. Fatty foods such as luncheon meats, condiments and salad dressings, and ground beef contributed more to the antioxidant intakes of current smokers than to those of the other 2 groups, whereas fruit and vegetables contributed less. Current smokers consumed the fewest numbers of servings of all nutrient-bearing groups in the food guide pyramid, except the meat group. CONCLUSION: Future interventions should target the clustering of cigarette smoking and other unhealthy lifestyle habits, eg, an imprudent diet.

Adult↗

PubMed2000

Zinc and copper intakes and their major food sources for older adults in the 1994-96 continuing survey of food intakes by individuals (CSFII).

Zinc and copper are two trace minerals essential for important biochemical functions and necessary for maintaining health throughout life. Several national food surveys revealed marginally to moderately low contents of both nutrients in the typical American diet. Using data from the respondents >/= 60 y old in the 1994-96 Continuing Survey of Food Intakes by Individuals (CSFII), we examined average dietary intakes of zinc, copper and relevant dietary factors; primary dietary contributors of zinc and copper; and Zn:Cu ratios of the primary dietary contributors. Data were analyzed with the use of a chi(2) test, Student's t test and multivariate analysis of covariance with Bonferroni correction. The daily zinc intake was 12 +/- 6.4 mg for men and 8.0 +/- 4.0 mg for women (P < 0.05); the daily copper intake was 1.3 +/- 0.7 mg for men and 1.0 +/- 0.5 mg for women (P < 0.05). Foods such as beef, ground beef, legumes, poultry, ready-to-eat and hot cereals, and pork constituted the major sources of zinc. Copper consumption was contributed mainly by legumes, potato and potato products, nuts and seeds, and beef. The less-than-recommended intakes of zinc and copper by the elderly were likely associated with age, low income and less education. The intakes of zinc and copper could be improved by more frequent consumption of food sources rich in these minerals. An inherent limitation of this study was the use of the 24-h dietary recall method, which may underestimate usual dietary intakes. Nonetheless, this study affirms the need for assessment of zinc and copper nutriture in the elderly.

Aged↗

PubMed2000

Molecular mimicry of human tumor antigen by heavy chain CDR3 sequence of the anti-idiotypic antibody.

We isolated and characterized an anti-idiotype monoclonal antibody (AR42.1) which is capable of mimicking a distinct and specific epitope of MUC-1 antigen. The cDNA sequences coding for the AR42.1 variable regions were determined. We found significant amino acid homology between complementary determining regions 3 (CDR3) in the heavy chain of AR42.1 and the determinant epitope sequence of MUC-1. This 10 amino acid sequence may represent an "internal image" of the anti-idiotype antibody to the MUC-1 antigen, and could be used for development of a MUC-1 surrogate for immunotherapy.

Animals↗

PubMed2000

Spontaneous speech recognition using a statistical coarticulatory model for the vocal-tract-resonance dynamics.

A statistical coarticulatory model is presented for spontaneous speech recognition, where knowledge of the dynamic, target-directed behavior in the vocal tract resonance is incorporated into the model design, training, and in likelihood computation. The principal advantage of the new model over the conventional HMM is the use of a compact, internal structure that parsimoniously represents long-span context dependence in the observable domain of speech acoustics without using additional, context-dependent model parameters. The new model is formulated mathematically as a constrained, nonstationary, and nonlinear dynamic system, for which a version of the generalized EM algorithm is developed and implemented for automatically learning the compact set of model parameters. A series of experiments for speech recognition and model synthesis using spontaneous speech data from the Switchboard corpus are reported. The promise of the new model is demonstrated by showing its consistently superior performance over a state-of-the-art benchmark HMM system under controlled experimental conditions. Experiments on model synthesis and analysis shed insight into the mechanism underlying such superiority in terms of the target-directed behavior and of the long-span context-dependence property, both inherent in the designed structure of the new dynamic model of speech.

Algorithms↗

PubMed2000

Reprogrammable recognition codes in bicoid homeodomain-DNA interaction.

We describe experiments to determine how the homeodomain of the Drosophila morphogenetic protein Bicoid recognizes different types of DNA sequences found in natural enhancers. Our chemical footprint analyses reveal that the Bicoid homeodomain makes both shared and distinct contacts with a consensus site A1 (TAATCC) and a nonconsensus site X1 (TAAGCT). In particular, the guanine of X1 at position 4 (TAAGCT) is protected by Bicoid homeodomain. We provide further evidence suggesting that the unique arginine at position 54 (Arg 54) of the Bicoid homeodomain enables the protein to recognize X1 by specifically interacting with this position 4 guanine. We also describe experiments to analyze the contribution of artificially introduced Arg 54 to DNA recognition by other Bicoid-related homeodomains, including that from the human disease protein Pitx2. Our experiments demonstrate that the role of Arg 54 varies depending on the exact homeodomain framework and DNA sequences. Together, our results suggest that Bicoid and its related homeodomains utilize distinct recognition codes to interact with different DNA sequences, underscoring the need to study DNA recognition by Bicoid-class homeodomains in an individualized manner.

Amino Acid Sequence↗

PubMed2000

Target selectivity of bicoid is dependent on nonconsensus site recognition and protein-protein interaction.

We describe experiments to compare the activities of two Drosophila homeodomain proteins, Bicoid (Bcd) and an altered-specificity mutant of Fushi tarazu, Ftz(Q50K). Although the homeodomains of these proteins share a virtually indistinguishable ability to recognize a consensus Bcd site, only Bcd can activate transcription from natural enhancer elements when assayed in both yeast and Drosophila Schneider S2 cells. Our analysis of chimeric proteins suggests that both the homeodomain of Bcd and sequences outside the homeodomain contribute to its ability to recognize natural enhancer elements. We further show that, unlike the Bcd homeodomain, the Ftz(Q50K) homeodomain fails to recognize nonconsensus sites found in natural enhancer elements. The defect of a chimeric protein containing the homeodomain of Ftz(Q50K) in place of that of Bcd can be preferentially restored by converting the nonconsensus sites in natural enhancer elements to consensus sites. Our experiments suggest that the biological specificity of Bcd is determined by combinatorial contributions of two important mechanisms: the nonconsensus site recognition function conferred by the homeodomain and the cooperativity function conferred primarily by sequences outside the homeodomain. A systematic comparison of different assay methods and enhancer elements further suggests a fluid nature of the requirements for these two Bcd functions in target selection.

Animals↗

PubMed2000

Expression of epidermal growth factor and transforming growth factor alpha in interfacial membranes retrieved at revision total hip arthroplasty.

BACKGROUND: The interfacial membrane between bone and implant has been shown to be a key tissue in the process of aseptic loosening of total hip arthroplasty. The cells within the interfacial membrane produce numerous inflammatory mediators which, through complex mechanisms, cause periprosthetic osteolysis and aseptic loosening. Both epidermal growth factor (EGF) and transforming growth factor alpha (TGFalpha) have similar biological functions. They have been found to stimulate bone resorption. OBJECTIVE: To investigate the presence, cellular localisation, and extent of expression of EGF and TGFalpha in interfacial membrane retrieved from revision total hip arthroplasty and compare it with that in synovial membrane from primary total hip arthroplasty. METHODS: Ten interfacial membranes and 10 synovial membranes were stained with avidin-biotin-peroxidase complex for EGF and TGFalpha. The staining process was done using the Lab Vision Autostainer. The results were measured by a semiautomatic VIDAS image analysis system. RESULTS: Immunoreactivity for both EGF and TGFalpha was found in the endothelial cells of blood vessels, macrophages, and fibroblasts, both in interfacial membranes and synovial membranes. However, the number of EGF (980 (370)) and TGFalpha (1070 (360)) positive cells per mm(2) was greater in interfacial membranes than in the synovial membranes (220 (200), 270 (100); p<0.01). CONCLUSION: It is suggested that owing to their increased expression in interfacial membrane, EGF and TGFalpha may have an important pathogenetic role in stimulating periprosthetic bone resorption in aseptic loosening of total hip arthroplasty.

Adult↗

PubMed2000

Asymptotic convergence rate of the EM algorithm for gaussian mixtures

It is well known that the convergence rate of the expectation-maximization (EM) algorithm can be faster than those of convention first-order iterative algorithms when the overlap in the given mixture is small. But this argument has not been mathematically proved yet. This article studies this problem asymptotically in the setting of gaussian mixtures under the theoretical framework of Xu and Jordan (1996). It has been proved that the asymptotic convergence rate of the EM algorithm for gaussian mixtures locally around the true solution Theta* is o(e(0. 5-epsilon)(Theta*)), where epsilon > 0 is an arbitrarily small number, o(x) means that it is a higher-order infinitesimal as x --> 0, and e(Theta*) is a measure of the average overlap of gaussians in the mixture. In other words, the large sample local convergence rate for the EM algorithm tends to be asymptotically superlinear when e(Theta*) tends to zero.

Journal Article↗

PubMed2000

Collagenases in different categories of peri-implant vertical bone loss.

The loosening of dental implants is associated with peri-implant vertical bone loss. The mechanisms and mediators of this bone destruction are not known. To test the hypothesis that collagenase-2 and collagenase-3 might be markers or maybe even mediators in this process, we measured collagenase-2 (time-resolved immunofluorometric assay) and collagenase-3 (quantitative immunoblot) in peri-implant sulcus fluid in 49 implant sites in 13 patients. Vertical bone loss was graded as being < 1 mm, from 1 to 3 mm, or > 3 mm. The severity of inflammation, as rated according to Gingival Index, did not correlate with the category of bone loss (p > 0.05). Collagenase-2 and collagenase-3 were higher (p < 0.05) in the group which had lost > 3 mm of bone than in the two other groups. Gingival Index is not a clinically important marker for bone loss, but collagenase-2 and collagenase-3 in peri-implant sulcus fluid are. They might participate in peri-implant osteolysis.

Adult↗

PubMed2000

Increased CYP2J expression and epoxyeicosatrienoic acid formation in spontaneously hypertensive rat kidney.

Epoxyeicosatrienoic acids (EETs) are major products of cytochrome P450 (CYP)-catalyzed metabolism of arachidonic acid in the kidney. The potent effect of EETs on renal vascular tone and tubular ion and water transport implicates their role in the regulation of renal function and blood pressure. The present study was designed to test the hypothesis that CYP-catalyzed EET formation was altered in the spontaneously hypertensive rat (SHR) kidney. The formation of 14,15- and 11,12-EET was approximately 2-fold higher in incubations of arachidonic acid with SHR renal cortical microsomes relative to microsomes from normotensive Wistar-Kyoto (WKY) rats. This was consistent with increased expression of a CYP2J2 immunoreactive protein in the SHR cortex and outer medulla. In contrast, there was no significant difference in the levels of the CYP2E and CYP2C epoxygenases in SHR and WKY kidneys. Protein and RNA analysis suggests that the CYP2J2 immunoreactive protein that is overexpressed in the SHR kidney is distinct from the known rat CYP2J isoforms. EET formation also was documented in vivo from measurements of urinary EET excretion. Importantly, the excretion rates of 14,15-, and 11,12-EETs were 2.5- and 1.8-fold higher, respectively, in SHR than WKY kidney. These studies provide both in vitro and in vivo evidence for increased EET formation in the SHR kidney and identify a novel CYP2J2 immunoreactive protein that is differentially expressed in the hypertensive kidney. In light of the known biological properties of the EETs, these findings may be important in elucidating the mechanisms that control renal vascular tone and tubular ion transport in the SHR.

8,11,14-Eicosatrienoic Acid↗

PubMed2000

A novel robust blood pressure control system.

A adaptive robust control of postoperative hypertension is presented to reduce the mean arterial blood pressure using vasoactive drugs. It is shown that the control algorithm provides stability-guaranteed regulation subject to infusion rate saturation. Simulation results under clinical conditions show that the control system exhibits strong robustness and is capable of reducing blood pressure.

Algorithms↗

PubMed2000

The fumonisin B1 content in corn from North China, a high-risk area of esophageal cancer.

Fusarium moniliforme is the primary fungus contaminating corn throughout the world. Fumonisin B1 (FB1) is the major metabolite of F. moniliforme. It has been shown that FB1 is the promoter and initiator of liver cancer in rat. The corn of Cixian, in Hebei Province, the high-risk area for esophageal cancer in China, is often contaminated by this fungus. A total of 21 corn samples were collected from households in the Cixian County. High levels of FB1 (88.90+/-13.1 microg/g) were found in 10 moldy samples, and low levels (1.40+/-0.50 microg/g) of FB1 were found in 11 apparently healthy corn samples. The positive detection rates of FB1 in moldy and normal samples were 100 and 90.9%, respectively. The frequency of FB1 contamination in the high-risk area is about twice that in the low-risk areas, and the average content of FB1 in samples from high-risk areas was approximately three times that from low-risk areas. Our data indicate that FB1-contaminated corn may be involved in the carcinogenesis of esophageal cancer in high-risk areas of North China.

Carboxylic Acids↗