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Biomedical subjects

D Kong

Publications and source records attributed to D Kong.

At least 19 recordsLinked to original sources
PubMed2005

Effect of cardiac lymph flow obstruction on cardiac collagen synthesis and interstitial fibrosis.

The effect of chronic cardiac lymphatic obstruction on the myocardial synthesis of collagen type I and III was investigated in a rabbit model. In the lymphatic obstruction group (n=16), plasma C-terminal propeptide type I procollagen (PICP) and N-terminal propeptide type III procollagen (PIIINP) were elevated at 7, 14 and 30 days after the operation (p<0.05). The elevated PICP and PIIINP returned to the pre-operation values 60 days after the operation. The myocardial expression of collagen type I and III mRNA were also enhanced in the lymphatic flow obstruction group. Plasma PICP, PIIINP and myocardial collagen type I and III mRNA remained unchanged in the control group (n=16). We concluded that chronic obstruction of cardiac lymph flow leads to enhanced myocardial collagen synthesis in rabbits. The enhanced collagen synthesis starts within seven days after lymphatic obstruction and subsides after 60 days.

Animals↗
PubMed2005

The ratios of individual chemicals in a mixture determine the degree of joint effect: the climax hypothesis.

A new hypothesis, the Climax Hypothesis, is proposed to describe how the ratios of individual chemicals influence the joint effects of chemical mixtures. This hypothesis is derived from a generalized approach using "isobolograms". With this hypothesis, one can predict that for a given mixture, a curvilinear correlation exists between the joint effects and the ratios of individual chemicals and that this curve has a climax at the equitoxic ratio. This prediction is supported by the observed toxicity to Vibrio fischeri of 18 mixtures (12 binary mixtures, 4 ternary mixtures, and 2 quaternary mixtures). With this prediction, the Climax Hypothesis has some promising applications such as controlling the discharge of effluents in environmental science, maximizing detoxifying effects in medicine, and optimizing combined pesticides in agriculture.

Data Interpretation, Statistical↗
PubMed2003

Observation of a near-threshold enhancement in the pp mass spectrum from radiative J/psi-->gammapp decays.

We observe a narrow enhancement near 2m(p) in the invariant mass spectrum of pp pairs from radiative J/psi-->gammapp decays. No similar structure is seen in J/psi-->pi(0)pp decays. The results are based on an analysis of a 58 x 10(6) event sample of J/psi decays accumulated with the BESII detector at the Beijing electron-positron collider. The enhancement can be fit with either an S- or P-wave Breit-Wigner resonance function. In the case of the S-wave fit, the peak mass is below 2m(p) at M=1859(+3)(-10) (stat)+5-25(syst) MeV/c(2) and the total width is Gamma<30 MeV/c(2) at the 90% confidence level. These mass and width values are not consistent with the properties of any known particle.

Journal Article↗
PubMed2003

Focused ultrasound (HIFU) induces localized enhancement of reporter gene expression in rabbit carotid artery.

The development of accurate, safe, and efficient gene delivery remains a major challenge towards the realization of gene therapeutic prevention and treatment of cardiovascular diseases. In this study, we investigated the ability of high-intensity focused ultrasound (HIFU), a form of mechanical wave transmission, to act as a noninvasive tool for the enhancement of in vivo gene transfer into rabbit carotid arteries. Segments of the common carotid arteries of New Zealand white rabbits were isolated and infused with plasmid DNA encoding the reporter beta-galactosidase either with or without the addition of ultrasound contrast agent consisting of small (approximately 2-5 microm) gas-filled human albumin microspheres to augment cavitation. Infused arteries were exposed to pulsed ultrasound for 1 min (frequency 0.85 MHz, burst length 50 ms, repetition frequency 1 Hz, duration 60 s, peak pressure amplitude of 15 MPa). At 6.3 MPa, HIFU enhanced gene expression eight-fold, and 17.5-fold in the presence of contrast. We found increasing amounts of beta-galactosidase expression in the carotid vessel with increasing pressure amplitude. This dose-response relation was present with and without contrast. Without contrast, no vessel damage was detected up to 15 MPa, while the addition of contrast induced side effects above a threshold of 6.3 MPa peak pressure. The entire procedure was feasible and safe for the animals, and the results suggest that HIFU has the potential to assist in the noninvasive spatial regulation of gene transfer into the vascular system.

Animals↗
PubMed2003

Randomized trial of an adherence programme for clients with HIV.

Our aim was to determine if a comprehensive adherence package improved self reported adherence to antiretroviral therapy. The adherence package included an education programme, individualized planning of regimens, and the opportunity for a patient to choose from a number of adherence aids and reminder devices. A randomized step wedge design was used. Forty-three individuals were randomized to begin the intervention over a five-month period. There was a substantial fall in the number of missed doses reported for the last four days (0.76 to 0.38, P =0.03) and last seven days (1.5 to 0.74, P =0.005) but not for the last 28 days (2.5 to 2.5, P =0.63). There was no statistical difference in the viral load or CD4 lymphocyte count in the period before or after the intervention. The Morisky score during the pre and post intervention periods was significantly different (P =0.006), 2.9 (SD 0.9) and 3.3 (SD 0.8) respectively. This adherence package improved self reported adherence during the last four and seven days.

Adult↗
PubMed2001

Hypermethylation of the hMLH1 gene promoter is associated with microsatellite instability in early human gastric neoplasia.

A significant portion of gastric cancers exhibit defective DNA mismatch repair, manifested as microsatellite instability (MSI). High-frequency MSI (MSI-H) is associated with hypermethylation of the human mut-L homologue 1 (hMLH1) mismatch repair gene promoter and diminished hMLH1 expression in advanced gastric cancers. However, the relationship between MSI and hMLH1 hypermethylation has not been studied in early gastric neoplasms. We therefore investigated hMLH1 hypermethylation, hMLH1 expression and MSI in a group of early gastric cancers and gastric adenomas. Sixty-four early gastric neoplasms were evaluated, comprising 28 adenomas, 18 mucosal carcinomas, and 18 carcinomas with superficial submucosal invasion but clear margins. MSI was evaluated using multiplex fluorescent PCR to amplify loci D2S123, D5S346, D17S250, BAT 25 and BAT 26. Methylation-specific PCR was performed to determine the methylation status of hMLH1. In two hypermethylated MSI-H cancers, hMLH1 protein expression was also evaluated by immunohistochemistry. Six of sixty-four early gastric lesions were MSI-H, comprising 1 adenoma, 4 mucosal carcinomas, and 1 carcinoma with superficial submucosal invasion. Two lesions (one adenoma and one mucosal carcinoma) demonstrated low-frequency MSI (MSI-L). The remaining 56 neoplasms were MSI-stable (MSI-S). Six of six MSI-H, one of two MSI-L, and none of thirty MSI-S lesions showed hMLH1 hypermethylation (P<0.001). Diminished hMLH1 protein expression was demonstrated by immunohistochemistry in two of two MSI-H hypermethylated lesions. hMLH1 promoter hypermethylation is significantly associated with MSI and diminished hMLH1 expression in early gastric neoplasms. MSI and hypermethylation-associated inactivation of hMLH1 are more prevalent in early gastric cancers than in gastric adenomas. Thus, hypermethylation-associated inactivation of the hMLH1 gene can occur early in gastric carcinogenesis.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Site-specific DNA binding of the Schizosaccharomyces pombe origin recognition complex is determined by the Orc4 subunit.

The mechanism by which origin recognition complexes (ORCs) identify replication origins was investigated using purified Orc proteins from Schizosaccharomyces pombe. Orc4p alone bound tightly and specifically to several sites within S. pombe replication origins that are genetically required for origin activity. These sites consisted of clusters of A or T residues on one strand but were devoid of either alternating A and T residues or GC-rich sequences. Addition of a complex consisting of Orc1, -2, -3, -5, and -6 proteins (ORC-5) altered neither Orc4p binding to origin DNA nor Orc4p protection of specific sequences. ORC-5 alone bound weakly and nonspecifically to DNA; strong binding required the presence of Orc4p. Under these conditions, all six subunits remained bound to chromatin isolated from each phase of the cell division cycle. These results reveal that the S. pombe ORC binds to multiple, specific sites within replication origins and that site selection, at least in vitro, is determined solely by the Orc4p subunit.

Base Sequence↗
PubMed2001

Anti-human platelet tetraspanin (CD9) monoclonal antibodies induce platelet integrin alpha IIb beta 3 activation in a Fc receptor-independent fashion.

OBJECTIVES: To characterize the activation of platelet integrin alpha IIb beta 3 induced by two anti-human platelet tetraspanin monoclonal antibodies (mAbs), HI117 and SJ9A4, and investigate their potential mechanism of action. METHODS: Using 125I-labeled human fibrinogen (Fg), specific Fg binding to human platelets induced by HI117 and SJ9A4 was measured. RESULTS: HI117 and SJ9A4 (10 micrograms/ml and 20 micrograms/ml) induced specific Fg binding to human platelets, suggesting that the two mAbs evoked activation of platelet integrin alpha IIb beta 3. Further study indicated that HI117 and SJ9A4 induced integrin alpha IIb beta 3 activation independent of platelet Fc-receptors, and that HI117 and SJ9A4-induced integrin alpha IIb beta 3 activation was inhibited by pretreatment of platelets with sphingosine, aspirin, apyrase, and/or PGI2. CONCLUSIONS: Anti-platelet tetraspanin (CD9) mAbs, HI117 and SJ9A4, can induce platelet integrin alpha IIb beta 3 activation independent of Fc-receptors. Three signaling pathways, namely thromboxane, secreted ADP, and cAMP pathways, may be involved in the process, with protein kinase C activation presumably being the common step of the three pathways.

Antibodies, Monoclonal↗
PubMed2000

Microsatellite instability in inflammatory bowel disease-associated neoplastic lesions is associated with hypermethylation and diminished expression of the DNA mismatch repair gene, hMLH1.

Twelve to 15% of sporadic colorectal cancers display defective DNA mismatch repair (MMR), manifested as microsatellite instability (MSI). In this group of cancers, promoter hypermethylation of the MMR gene hMLH1 is strongly associated with, and believed to be the cause of, MSI. A subset of colorectal neoplastic lesions arising in inflammatory bowel disease (IBD) is also characterized by MSI. We wished to determine whether hMLH1 hypermethylation was associated with diminished hMLH1 protein expression and MSI in IBD neoplasms. We studied 148 patients with IBD neoplasms, defined as carcinoma or dysplasia occurring in patients with ulcerative colitis or Crohn's disease. MSI was evaluated using multiplex fluorescent PCR to amplify loci D2S123, BAT-25, BAT-26, D5S346, and D17S250 in all cases. Lesions were characterized as high-frequency MSI (MSI-H) if they manifested instability at two or more loci, low-frequency MSI (MSI-L) if unstable at only one locus, or MS-stable (MSS) if showing no instability at any loci. Methylation-specific PCR was performed to determine the methylation status of the hMLH1 promoter region. hMLH1 protein expression was also evaluated by immunohistochemistry. Thirteen (9%) of 148 neoplasms arising in IBD were MSI-H, comprising 11 carcinomas and 2 dysplastic lesions. Sixteen additional lesions (11%) were MSI-L, comprising 11 carcinomas and 5 dysplastic lesions. The remaining 118 neoplasms (80%) were MSS. Six (46%) of 13 MSI-H, 1 (6%) of 16 MSI-L, and 4 (15%) of 27 MSS lesions showed hMLH1 hypermethylation (P = 0.013). Diminished hMLH1 protein expression in neoplastic cell nuclei relative to surrounding normal cell nuclei was demonstrated immunohistochemically in four of four (100%) hypermethylated lesions tested. In IBD neoplasia, hMLH1 promoter hypermethylation occurs frequently in the setting of MSI, particularly MSI-H. Furthermore, hMLH1 hypermethylation and MSI are strongly associated with diminished hMLH1 protein expression in IBD neoplasms. These findings suggest that hMLH1 hypermethylation causes defective DNA MMR in at least a subset of IBD neoplasms.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Distinct methylation patterns of two APC gene promoters in normal and cancerous gastric epithelia.

The adenomatous polyposis coli (APC) tumor suppressor gene is mutationally inactivated in both familial and sporadic forms of colorectal cancers. In addition, hypermethylation of CpG islands in the upstream portion of APC, a potential alternative mechanism of tumor suppressor gene inactivation, has been described in colorectal cancer. Because a subset of both gastric and colorectal cancers display the CpG island methylator phenotype, we hypothesized that epigenetic inactivation of APC was likely to occur in at least some gastric cancers. APC exhibits two forms of transcripts from exons 1A and 1B in the stomach. Therefore, we investigated CpG island methylation in the sequences upstream of exons 1A and 1B, i.e., promoters 1A and 1B, respectively. We evaluated DNAs from 10 gastric cancer cell lines, 40 primary gastric cancers, and 40 matching non-cancerous gastric mucosae. Methylated alleles of promoter 1A were present in 10 (100%) of 10 gastric cancer cell lines, 33 (82.5%) of 40 primary gastric cancers, and 39 (97.5%) of 40 noncancerous gastric mucosae. In contrast, promoter 1B was unmethylated in all of these same samples. APC transcripts from exon 1A were not expressed in nine of the 10 methylated gastric cancer cell lines, whereas APC transcripts were expressed from exon 1B. Thus, expression from a given promoter correlated well with its methylation status. We conclude that in contrast to the colon, methylation of promoter 1A is a normal event in the stomach; moreover, promoter 1B is protected from methylation in the stomach and thus probably does not participate in this form of epigenetic APC inactivation.

Adolescent↗
PubMed2000

E-Cadherin gene promoter hypermethylation in primary human gastric carcinomas.

BACKGROUND: E (epithelial)-cadherin, the cell adhesion molecule also considered a potential invasion/metastasis suppressor, is mutationally inactivated in nearly half of all undifferentiated-scattered (diffuse-type) gastric carcinomas. In addition, silencing of E-cadherin by CpG methylation within its promoter region has been reported in several gastric carcinoma cell lines. We investigated the methylation status of the E-cadherin promoter region in 53 primary human gastric carcinomas. METHODS: Hypermethylation of the E-cadherin promoter was determined by utilizing methylation-specific polymerase chain reaction (PCR)-single-strand conformation polymorphism (MSP-SSCP) analysis followed by direct sequencing of PCR products. Expression of E-cadherin was studied by western blot analysis. All statistical tests were two-sided. RESULTS: Hypermethylation of the E-cadherin promoter was evident in 27 (51%) of 53 primary gastric carcinomas examined by MSP-SSCP. It occurred more frequently in carcinomas of the undifferentiated-scattered type (in 15 [83%] of 18) than in other histologic subtypes (in 12 [34%] of 35) (P =.0011, Fisher's exact test), and it was present at similar rates in early (in six [60%] of 10) versus advanced (in 21 [49%] of 43) carcinomas (P =.73, Fisher's exact test). Methylation occurring at all cytosine-guanosine sequences (CpGs) near the transcriptional start site was confirmed in six of six tumors examined by bisulfite-DNA sequencing, including two early gastric carcinomas. In addition, loss or diminished expression of E-cadherin was confirmed by western blotting in four of the six tumor tissues demonstrating hypermethylation. CONCLUSIONS: The E-cadherin promoter frequently undergoes hypermethylation in human gastric cancers, particularly those of the undifferentiated-scattered histologic subtype. E-cadherin promoter hypermethylation is associated with decreased expression and may occur early in gastric carcinogenesis.

Blotting, Western↗
PubMed2000

Prediction of myocardial perfusion abnormalities by quantitative regional function using a radionuclide angiography database: a comparison with wall motion analysis.

PURPOSE: Myocardial perfusion and functional information during the same study is now feasible. A new assessment of regional ejection fraction at rest and peak exercise by first-pass radionuclide angiography using a "normal" database file has been developed. OBJECTIVE: This study was performed to assess the relation between this new method of quantitative regional ejection fraction and myocardial perfusion abnormalities and to compare this new technique with visual analysis of regional wall motion. METHODS: Consecutive patients (n = 126) with simultaneous first-pass radionuclide angiography and perfusion SPECT imaging were studied at rest and peak exercise using a same-day protocol. The area under the receiver-operator characteristic curve (C index) was used to assess the concordance probability between perfusion and functional measurements, and logistic regression models were used to examine the ability of functional variables to predict perfusion results. RESULTS: A high concordance was found between the visual analysis of wall motion and perfusion abnormalities (C index = 0.796), and also between regional ejection fraction and perfusion defects (C index = 0.784). The maximal predictive power of functional variables was obtained by combining wall motion analysis and regional ejection fraction (C index = 0.859). Regional ejection fraction contributed, with 20% more information than provided by wall motion analysis alone (chi2 = 9.2, P = 0.0025). CONCLUSIONS: Quantitative regional ejection fraction using a normal database file has a strong relation to perfusion abnormalities and provides incremental information to regional wall motion analysis for predicting perfusion abnormalities. This new technique should be regarded as a potential adjunct to functional studies to evaluate patients with ischemic heart disease.

Cardiac Catheterization↗
PubMed2000

Mismatch cleavage detects pathogenic microorganisms.

When a DNA probe hybridizes a DNA target and generates a G/A mismatch in the probe-target DNA heteroduplex, the mismatch enzyme, mutY, will cut the A base at the site of the mismatch. This specific cleavage at the mismatched A on the known probe will reveal the complementary DNA sequences of the targets. This study shows mismatch cleavage assays identify the complementary sequence of cryptic plasmid target in the extract of chlamydia infected cells in culture. In addition, the specific cleavage at a single base permits differentiation of two sequences with one base difference. This was shown in differentiating the subtypes of human immunodeficiency virus (HIV) type 1. The addition of amines in the assays increases the sensitivity by freeing the target for recycling. The combined assay system of high sensitivity and demonstrated specificity allows further evaluation for direct identification of pathogenic microorganisms in patient samples.

Acetates↗
PubMed1999

Identification and reconstitution of the origin recognition complex from Schizosaccharomyces pombe.

The origin recognition complex (ORC), first identified in Saccharomyces cerevisiae (sc), is a six-subunit protein complex that binds to DNA origins. Here, we report the identification and cloning of cDNAs encoding the six subunits of the ORC of Schizosaccharomyces pombe (sp). Sequence analyses revealed that spOrc1, 2, and 5 subunits are highly conserved compared with their counterparts from S. cerevisiae, Xenopus, Drosophila, and human. In contrast, both spOrc3 and spOrc6 subunits are poorly conserved. As reported by Chuang and Kelly [(1999) Proc. Natl. Acad. Sci. USA 96, 2656-2661], the C-terminal region of spOrc4 is also conserved whereas the N terminus uniquely contains repeats of a sequence that binds strongly to AT-rich DNA regions. Consistent with this, extraction of S. pombe chromatin with 1 M NaCl, or after DNase I treatment, yielded the six-subunit ORC, whereas extraction with 0.3 M resulted in five-subunit ORC lacking spOrc4p. The spORC can be reconstituted in vitro with all six recombinant subunits expressed in the rabbit reticulocyte system. The association of spOrc4p with the other subunits required the removal of DNA from reaction mixture by DNase I. This suggests that a strong interaction between spOrc4p and DNA can prevent the isolation of the six-subunit ORC. The unique DNA-binding properties of the spORC may contribute to our understanding of the sequence-specific recognition required for the initiation of DNA replication in S. pombe.

Amino Acid Sequence↗
PubMed1999

[Effects of long-term exposure to lower concentration of carbon disulfide on cardiovascular system of workers in a viscose rayon factory].

An epidemiological cross-sectional study was conducted on 99 workers exposed to lower concentration of carbon disulfide in a viscose rayon factory for a long time and 28 non-exposed ones in the same factory. Blood pressure, serum lipoproteins and electrocardiograph were detected. The results showed that neither diastolic blood pressure nor systolic one between exposed group and control group was obviously different All indicators of serum lipids and lipoproteins were not significantly different except the lipoprotein(a) of exposed group was significantly higher than that of control group, and the risk of abnormal electrocardiogram in the workers exposed to carbon disulfide was 1.1 times of those non-exposed ones but with no statistical significance. The results suggest that lipoprotein(a) can be used as a sensitive indicator for the cardiotoxic effects of carbon disulfide.

Adult↗
PubMed1999

Expression of the wild-type insulin-like growth factor II receptor gene suppresses growth and causes death in colorectal carcinoma cells.

The insulin-like growth factor II receptor (IGFIIR) has been implicated as a tumor suppressor gene in human malignancy. Frequent mutation, loss of heterozygosity, and microsatellite instability (MSI) directly affecting the IGFIIR gene have been reported in several primary human tumor types. However, to our knowledge, dynamic functional evidence of a growth-suppressive role for IGFIIR has not yet been provided. We identified one MSI-positive colorectal carcinoma cell line, SW48, with monoallelic mutation in IGFIIR identical to that seen in primary colorectal carcinomas. A zinc-inducible construct containing the wild-type IGFIIR cDNA was stably transfected into SW48 cells. Growth rate and apoptosis were compared between zinc-treated, untreated, and untransfected cells. A twofold increase in IGFIIR protein expression was detected after zinc treatment in discrete clonal isolates of transfected SW48 cells. Moreover, zinc induction of exogenous wild-type IGFIIR expression reproducibly decreased growth rate and increased apoptosis. These data prove that wild-type IGFIIR functions as a growth suppressor gene in colorectal cancer cells and provide dynamic in vitro functional support for the hypothesis that IGFIIR is a human growth suppressor gene.

Adenocarcinoma↗
PubMed1999

Low prevalence of the APC I1307K sequence in Jewish and non-Jewish patients with inflammatory bowel disease.

A germline sequence alteration at codon 1307 of the APC gene (I1307K) has been reported in 6-7% of the Ashkenazi Jewish population in the United States. This alteration is believed to predispose the APC gene to a secondary mutation at the same locus, resulting in an increased risk of colorectal carcinoma. There is an increased risk of colorectal carcinoma in patients with inflammatory bowel disease (IBD), a relatively large proportion of whom are Ashkenazi Jews. We therefore sought to determine whether the I1307K sequence variant occurred in the germline DNA of IBD patients. To our surprise, we found this sequence in only two of 267 patients with IBD (0.7%), occurring in only 1.5% of Jewish IBD patients. The I1307K sequence variant was not found in 67 patients with esophageal cancer, 53 patients with gastric carcinoma (13 MSI-H and 44 MSI-negative), or ten patients with sporadic MSI-H colon cancer. These findings suggest that the I1307K sequence is relatively rare in the germline of Jewish as well as non-Jewish IBD patients. It does not appear to contribute to the increased colorectal cancer risk present in these patients.

Colorectal Neoplasms↗