Biomedical subjects

David Zhang

Publications and source records attributed to David Zhang.

35 records · Page 2Linked to original sources

PubMed2004

Targeted alpha therapy for cancer.

Targeted alpha therapy (TAT) offers the potential to inhibit the growth of micrometastases by selectively killing isolated and preangiogenic clusters of cancer cells. The practicality and efficacy of TAT is tested by in vitro and in vivo studies in melanoma, leukaemia, colorectal, breast and prostate cancers, and by a phase 1 trial of intralesional TAT for melanoma. The alpha-emitting radioisotope used is Bi-213, which is eluted from the Ac-225 generator and chelated to a cancer specific monoclonal antibody (mab) or protein (e.g. plasminogen activator inhibitor-2 PAI2) to form the alpha-conjugate (AC). Stable alpha-ACs have been produced which have been tested for specificity and cytotoxicity in vitro against melanoma (9.2.27 mab), leukaemia (WM60), colorectal (C30.6), breast (PAI2, herceptin), ovarian (PAI2, herceptin, C595), prostate (PAI2, J591) and pancreatic (PAI2, C595) cancers. Subcutaneous inoculation of 1-1.5 million human cancer cells into the flanks of nude mice causes tumours to grow in all mice. Tumour growth is compared for untreated controls, nonspecific AC and specific AC, for local (subcutaneous) and systemic (tail vein or intraperitoneal) injection models. The 213Bi-9.2.27 AC is injected into secondary skin melanomas in stage 4 patients in a dose escalation study to determine the effective tolerance dose, and to measure kinematics to obtain the equivalent dose to organs. In vitro studies show that TAT is one to two orders of magnitude more cytotoxic to targeted cells than non-specific ACs, specific beta emitting conjugates or free isotopes. In vivo local TAT at 2 days post-inoculation completely prevents tumour formation for all cancers tested so far. Intra-lesional TAT can completely regress advanced sc melanoma but is less successful for breast and prostate cancers. Systemic TAT inhibits the growth of sc melanoma xenografts and gives almost complete control of breast and prostate cancer tumour growth. Intralesional doses up to 450 microCi in human patients are effective in regressing melanomas, with no concomitant complications. These results point to the application of local and systemic TAT in the management of secondary cancer. Results of the phase 1 clinical trial of TAT of subcutaneous, secondary melanoma indicate proof of the principle that TAT can make tumours in patients regress.

Alpha Particles↗

PubMed2004

Inhibition of cyclooxygenase-2 activity in head and neck cancer cells by genistein.

Genistein, rich in soybean, has been reported to have anti-cancer activity on several cancers. However, the molecular mechanism of its anti-cancer activity still remains unclear. We investigated the effect of genistein on a human oral squamous carcinoma line (SCC-25), and demonstrated that genistein inhibited SCC-25 cell growth via G2/M phase arrest. We observed a significant decrease of proliferating cell nuclear antigen expression in these cells after treatment, but no significant change in the number of apoptotic cells, indicating that the major action of genistein is inhibition of cancer cell proliferation. We also observed a high level of prostaglandin E2 (PGE2) in these cells and PGE2 synthesis in SCC-25 cells was significantly suppressed by genistein. We demonstrated that genistein directly inhibited cycloxygenase-2 (COX-2) activity, an inducible enzyme that converts arachidonic acid to prostaglandins, similar to the action of celecoxib, a selective COX-2 inhibitor. However, the anticancer activity of genistein was much weaker than that of indomethacin (non-selective COX inhibitor), celecoxib and baicalein (flavonoid isolated from Scutellaria baicalensis). These results suggested that genistein might be useful as a chemopreventive agent rather than a chemotherapeutic agent.

Apoptosis↗

PubMed2004

DNA content in embryo and endosperm of maize kernel (Zea mays L.): impact on GMO quantification.

PCR-based techniques are the most widely used methods for the quantification of genetically modified organisms (GMOs) through the determination of the ratio of transgenic DNA to total DNA. It is shown that the DNA content per mass unit is significantly different among 10 maize cultivars. The DNA contents of endosperms, embryos, and teguments of individual kernels from 10 maize cultivars were determined. According to our results, the tegument's DNA ratio reaches at maximum 3.5% of the total kernel's DNA, whereas the endosperm's and the embryo's DNA ratios are nearly equal to 50%. The embryo cells are diploid and made of one paternal and one maternal haploid genome, whereas the endosperm is constituted of triploid cells made of two maternal haploid genomes and one paternal haploid genome. Therefore, it is shown, in this study, that the accuracy of the GMO quantification depends on the reference material used as well as on the category of the transgenic kernels present in the mixture.

DNA, Plant↗

PubMed2004

Fulminant and fatal gas gangrene of the stomach in a healthy live liver donor.

A 57-year-old male with a history of hypercholesterolemia and anxiety but otherwise in good health volunteered to donate the right lobe of his liver to his brother. The operation was performed uneventfully, without transfusion. Postoperatively he did well, until he developed tachycardia, profound hypotension, and coffee ground emesis on postoperative day 3. Despite resuscitative measures, he arrested and expired. Autopsy demonstrated gas gangrene of the stomach as the underlying cause of the hemorrhage and numerous colonies of Gram-positive bacilli were identified. Subsequent polymerase chain reaction (PCR) analysis identified these bacteria to be Clostridium perfringens (C. perfringens) type D. This patient's death was devastating, both to his family and his medical team. The impact of his death has transcended that of an individual occurrence. In conclusion, herein we present the facts and discuss this extraordinary example of florid clostridial infection and toxin-mediated shock. It was completely unexpected and probably unpreventable, and its cause was almost inconceivable.

Clostridium perfringens↗

PubMed2004

Age- and sex-dependent changes in pulse pressure in fowl aorta.

Chickens (males more than females) have higher blood pressure (BP) than most mammals and spontaneously develop vascular neointimal plaques (NP) and diffuse subendothelial thickening in the lower segment of the abdominal aorta (AbA, referred to as 'NP-prone area') that partly resemble atherosclerotic lesions in mammals. NP areas, which are larger in males, have a causal relationship with incremental increases in BP during maturation. We hypothesize that decreased wall distensibility and altered hemodynamic forces at the NP-prone area may contribute to the NP formation. We measured pressure pulse wave (PW) and systolic and diastolic BP along the descending aorta in anesthetized chickens at different ages using an intravascular microtip transducer and calculated pulse pressure (PP) as an indicator for artery distensibility. At all ages examined and in both sexes, the PW showed a sharper peak at the more peripheral locations and the amplitude of the PW increased as it descended the aorta. PP, expressed as relative increases from the PP in the aortic arch (%), was 40.4+/-12.6 and 71.4+/-18.6 at the AbA and ischiadic artery, respectively, in young males (24-27 weeks); 23.5+/-8.6 and 43.8+/-16.2 in adults (72-75 weeks); and 5.4+/-3.4 and 9.1+/-4.9 in chicks (5-7 weeks). Location-dependent increases in PP were significantly higher in young males (P<0.05). The PP increases in females were not different among the three age groups. The contour of the PW in the proximal aorta changes in older birds, exhibiting steeper increases in the ascending and descending limbs, suggesting that faster wave reflection from the periphery augments peak systolic pressure. NP was most frequently seen in the lower segment of the abdominal aorta in older males. These results suggest that: (1) site-dependent increases in PP amplitude are marked in young males, possibly reflecting a reduction in arterial wall elasticity enhanced by incremental rises in BP, and (2) NP formation may contribute to the stiffness of aortic walls in the NP-prone area.

Age Factors↗

PubMed2004

Frequency of douching and risk of bacterial vaginosis in African-American women.

OBJECTIVE: Frequent vaginal douching has been associated with bacterial vaginosis. We investigated whether infrequent douching is also a risk factor for bacterial vaginosis. METHODS: In this cross-sectional study, we recruited 411 African-American women of reproductive age who were visiting gynecologic or family planning clinics of 2 hospitals in New York City from 1999 to 2001. Detailed information on demographic characteristics, feminine hygiene practice, contraceptive use, and reproductive and medical history was collected through in-person interview. Pelvic examinations and laboratory tests on vaginal secretions were performed. Bacterial vaginosis was defined as Gram stain score of 7 or greater. RESULTS: The overall prevalence of bacterial vaginosis in this population was 27%, similar to the national average. Water-vinegar solution was the most common douche. Although one half of the subjects reported douching regularly, only 2% douched frequently (once per week or more). Frequent douching in the past 3 months had a prevalence ratio of bacterial vaginosis of 2.35 (95% confidence interval 0.98-5.63). However, douching less than once per week was not associated with bacterial vaginosis. CONCLUSION: Douching less than once per week, particularly with a water-vinegar douche, is not associated with bacterial vaginosis in this African-American population. LEVEL OF EVIDENCE: III

Adolescent↗

PubMed2004

Computerized tongue diagnosis based on Bayesian networks.

Tongue diagnosis is an important diagnostic method in traditional Chinese medicine (TCM). However, due to its qualitative, subjective and experience-based nature, traditional tongue diagnosis has a very limited-application in clinical medicine. Moreover, traditional tongue diagnosis is always concerned with the identification of syndromes rather than with the connection between tongue abnormal appearances and diseases. This is not well understood in Western medicine, thus greatly obstruct its wider use in the world. In this paper, we present a novel computerized tongue inspection method aiming to address these problems. First, two kinds of quantitative features, chromatic and textural measures, are extracted from tongue images by using popular digital image processing techniques. Then, Bayesian networks are employed to model the relationship between these quantitative features and diseases. The effectiveness of the method is tested on a group of 455 patients affected by 13 common diseases as well as other 70 healthy volunteers, and the diagnostic results predicted by the previously trained Bayesian network classifiers are reported.

Artificial Intelligence↗

PubMed2004

Two-dimensional PCA: a new approach to appearance-based face representation and recognition.

In this paper, a new technique coined two-dimensional principal component analysis (2DPCA) is developed for image representation. As opposed to PCA, 2DPCA is based on 2D image matrices rather than 1D vectors so the image matrix does not need to be transformed into a vector prior to feature extraction. Instead, an image covariance matrix is constructed directly using the original image matrices, and its eigenvectors are derived for image feature extraction. To test 2DPCA and evaluate its performance, a series of experiments were performed on three face image databases: ORL, AR, and Yale face databases. The recognition rate across all trials was higher using 2DPCA than PCA. The experimental results also indicated that the extraction of image features is computationally more efficient using 2DPCA than PCA.

Algorithms↗

PubMed2004

Characterization of palmprints by wavelet signatures via directional context modeling.

The palmprint is one of the most reliable physiological characteristics that can be used to distinguish between individuals. Current palmprint-based systems are more user friendly, more cost effective, and require fewer data signatures than traditional fingerprint-based identification systems. The principal lines and wrinkles captured in a low-resolution palmprint image provide more than enough information to uniquely identify an individual. This paper presents a palmprint identification scheme that characterizes a palmprint using a set of statistical signatures. The palmprint is first transformed into the wavelet domain, and the directional context of each wavelet subband is defined and computed in order to collect the predominant coefficients of its principal lines and wrinkles. A set of statistical signatures, which includes gravity center, density, spatial dispersivity and energy, is then defined to characterize the palmprint with the selected directional context values. A classification and identification scheme based on these signatures is subsequently developed. This scheme exploits the features of principal lines and prominent wrinkles sufficiently and achieves satisfactory results. Compared with the line-segments-matching or interesting-points-matching based palmprint verification schemes, the proposed scheme uses a much smaller amount of data signatures. It also provides a convenient classification strategy and more accurate identification.

Algorithms↗

PubMed2004

An improved LDA approach.

Linear discrimination analysis (LDA) technique is an important and well-developed area of image recognition and to date many linear discrimination methods have been put forward. Despite these efforts, there persist in LDA at least three areas of weakness. The first weakness is that not all the discrimination vectors that are obtained are useful in pattern classification. Second, it remains computationally expensive to make the discrimination vectors completely satisfy statistical uncorrelation. The third weakness is that it is necessary to select the appropriate principal components. In this paper, we propose to improve discrimination technique in these three areas and to that end present an improved LDA (ILDA) approach which synthesizes these improvements. Experimental results on different image databases demonstrate that our improvements on LDA are efficient, and that ILDA outperforms other state-of-the-art linear discrimination methods.

Algorithms↗

PubMed2004

A face and palmprint recognition approach based on discriminant DCT feature extraction.

In the field of image processing and recognition, discrete cosine transform (DCT) and linear discrimination are two widely used techniques. Based on them, we present a new face and palmprint recognition approach in this paper. It first uses a two-dimensional separability judgment to select the DCT frequency bands with favorable linear separability. Then from the selected bands, it extracts the linear discriminative features by an improved Fisherface method and performs the classification by the nearest neighbor classifier. We detailedly analyze theoretical advantages of our approach in feature extraction. The experiments on face databases and palmprint database demonstrate that compared to the state-of-the-art linear discrimination methods, our approach obtains better classification performance. It can significantly improve the recognition rates for face and palmprint data and effectively reduce the dimension of feature space.

Algorithms↗

PubMed2004

Anticancer activities of Oldenlandia diffusa.

OBJECTIVES: To investigate the anticancer activities of a Chinese herb, Oldenlandia diffusa (Bai Hua She She Cao). METHODS: The water extract of the raw herb Oldenlandia diffusa was used in this study. The in vitro anti-proliferative activities of the extract were tested against eight cancer cell lines and one normal cell line. Microscopic examination and DNA ladder analysis were carried out to determine the pro-apoptotic effect of the extract. In vivo studies were carried out to examine the anticancer activities of the extract using C57BL/6j mice bearing B16-F10 lung metastasis. Oldenlandia diffusa extract was given at the dose level of 5 g raw material/kg on Days 3-12 by oral gavage and the extent of lung metastases were examined on Day 14. RESULTS: The extract exhibited a strong antiproliferative activity against all cancer cell lines tested. The concentrations of growth inhibition at 50% (IC(50)) ranged from 7 to 25 mg raw material/ml after 48-hour treatment. The extract had a very limited cytotoxicity (10% inhibition) on the normal pancreatic cells even at the concentration of 50 mg/mL. Apoptosis in B16-F10 cells after treatment with the extract was observed by microscopic examination and DNA ladder assays. Oral administration of the herbal extract effectively reduced B16-F10 cell growth in the lungs of C57Bl/j mice with a 70% reduction in lung metastases (p < 0.001). CONCLUSIONS: Oldenlandia diffusa extract effectively inhibited the growth of all the eight cancer cell lines and induced significant increase of apoptosis. The extract exhibited minimum toxic effect on normal pancreatic cells. Furthermore, there was a significant inhibition of lung metastases in the animal model with no noticeable adverse effects. The herb extract could be a potential anticancer agent.

Animals↗

PubMed2002

Comparison of DNA and RNA extraction methods for mummified tissues.

Nucleic acids extracted from mummified tissues are valuable materials for the study of ancient human beings. Significant difficulty in extracting nucleic acids from mummified tissues has been reported due to chemical modification and degradation. The goal of this study was to determine a method that is more efficient for DNA and RNA extraction from mummified tissues. Twelve mummy specimens were analyzed with 9 different nucleic acid extraction methods, including guanidium thiocyanate (GTC) and proteinase K/detergent based methods prepared in our laboratory or purchased. Glyceraldehyde 3-phosphate dehydrogenase DNA and beta-actin RNA were used as markers for the presence of adequate DNA and RNA, respectively, for PCR and RT-PCR amplification. Our results show that 5 M GTC is more efficient of releasing nucleic acids from mummified tissue than proteinase K/detergent, and phenol/chloroform extraction with an additional chloroform step is more efficient than phenol/chloroform along. We were able to isolate DNAs from all 12 specimens and RNAs from 8 of 12 specimens, and the nucleic acids were sufficient for PCR and RT-PCR analysis. We further tested hepatitis viruses including hepatitis B virus, hepatitis C virus, hepatitis G virus, and TT virus DNA, and fail to detect these viruses in all 12 specimens.

Chloroform↗

PubMed2002

Cytochrome p-450 epoxygenase metabolites of docosahexaenoate potently dilate coronary arterioles by activating large-conductance calcium-activated potassium channels.

Diets enriched in docosahexaenoic acid, a major n-3 fatty acid in fish oil, have hypotensive properties. One mechanism that can lower blood pressure is the direct dilation of arterioles by docosahexaenoic metabolites. Vascular endothelium contains cytochrome P-450 epoxygenases that transform the n-6 fatty acid arachidonate into epoxyeicosatrienoic acids (EETs), potent dilators of coronary arterioles and activators of large-conductance calcium-activated potassium (BK(Ca)) channels. To test whether analogous activations occur for docosahexaenoate, we compared the potency of docosahexaenoate and its five cytochrome P-450 epoxygenase metabolites, epoxydocosapentaenoates (EDPs), in dilating porcine coronary arterioles (<135 microm in diameter) precontracted with endothelin. The five EDP regioisomers had dilation EC(50) values ranging from 0.5 to 24 pM (n = 5-6). In contrast, the EDP hydrolysis product 13,14-dihydroxydocosapentaenoic acid (13,14-DHDP) had an EC(50) value of 30 +/- 22 nM (n = 7), whereas docosahexaenoate only dilated vessels at > or =1.0 microM (n = 7). Using patch-clamp techniques in the inside-out configuration, we determined that the 13,14-EDP regioisomer potently activated (EC(50) value of 6.6 +/- 0.6 pM; n = 5) BK(Ca) channels in myocytes from the porcine coronary arterioles. Moreover, 13,14-EDP potently activated BK(Ca) channels in myocytes from rat coronary small arteries (150-300 microm in diameter); with an EC(50) value of 2.2 +/- 0.6 pM (n = 7), 13,14-EDP was 1000-fold more potent than EETs in activating BK(Ca) channels. We conclude that EDPs potently dilate coronary microvessels and are the most potent fatty epoxides known to activate BK(Ca) channels in coronary smooth muscle cells. Both actions may contribute to the hypotensive effects of dietary fish oils.

Algorithms↗

PubMed2002

Detection of mycobacterial DNA in Andean mummies.

The identification of genetic material from pathogenic organisms in ancient tissues provides a powerful tool for the study of certain infectious diseases in historic populations. We have obtained tissue samples from the genital areas of 12 mummies in the American Museum of Natural History collection in New York, N.Y. The mummies were excavated in the Andes Mountain region of South America, and radiocarbon dating estimates that the mummies date from A.D. 140 to 1200. DNAs were successfully extracted from all tissues and were suitable for PCR analysis. PCRs were carried out to detect Mycobacterium tuberculosis complex and mycobacteria other than M. tuberculosis (MOTB). M. tuberculosis complex was detected in 2 out of 12 samples, and MOTB were detected in 7 samples. This study confirmed the adequate preservation of genetic material in mummified tissues and the existence of mycobacteria, including M. tuberculosis, in historic populations in South America.

DNA, Bacterial↗

PubMedDate not supplied

Mesh simplification with hierarchical shape analysis and iterative edge contraction.

This paper presents a novel mesh simplification algorithm. It decouples the simplification process into two phases: shape analysis and edge contraction. In the analysis phase, it imposes a hierarchical structure on a surface mesh by uniform hierarchical partitioning, marks the importance of each vertex in the hierarchical structure, and determines the affected regions of each vertex at the hierarchical levels. In the contraction phase, it also divides the simplification procedure into two steps: half-edge contraction and optimization. In the first step, memoryless quadric metric error and the importance of vertices in the hierarchical structure are combined to determine one operation of half-edge contraction. In the second step, it repositions the vertices in the half-edge simplified mesh by minimizing the multilevel synthesized quadric error on the corresponding affected regions from the immediately local to the more global. The experiments illustrate the competitive results.

Algorithms↗

PubMedDate not supplied

Mesh parameterization by minimizing the synthesized distortion metric with the coefficient-optimizing algorithm.

The parameterization of a 3D mesh into a planar domain requires a distortion metric and a minimizing process. Most previous work has sought to minimize the average area distortion, the average angle distortion, or a combination of these. Typical distortion metrics can reflect the overall performance of parameterizations but discount high local deformations. This affects the performance of postprocessing operations such as uniform remeshing and texture mapping. This paper introduces a new metric that synthesizes the average distortions and the variances of both the area deformations and the angle deformations over an entire mesh. Experiments show that, when compared with previous work, the use of synthesized distortion metric performs satisfactorily in terms of both the average area deformation and the average angle deformation; furthermore, the area and angle deformations are distributed more uniformly. This paper also develops a new iterative process for minimizing the synthesized distortion, the coefficient-optimizing algorithm. At each iteration, rather than updating the positions immediately after the local optimization, the coefficient-optimizing algorithm first update the coefficients for the linear convex combination and then globally updates the positions by solving the Laplace system. The high performance of the coefficient-optimizing algorithm has been demonstrated in many experiments.

Algorithms↗