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Biomedical subjects

J L Wang

Publications and source records attributed to J L Wang.

At least 73 records · Page 4Linked to original sources
PubMed2000

Structure-based discovery of an organic compound that binds Bcl-2 protein and induces apoptosis of tumor cells.

Bcl-2 and related proteins are key regulators of apoptosis or programmed cell death implicated in human disease including cancer. We recently showed that cell-permeable Bcl-2 binding peptides could induce apoptosis of human myeloid leukemia in vitro and suppress its growth in severe combined immunodeficient mice. Here we report the discovery of HA14-1, a small molecule (molecular weight = 409) and nonpeptidic ligand of a Bcl-2 surface pocket, by using a computer screening strategy based on the predicted structure of Bcl-2 protein. In vitro binding studies demonstrated the interaction of HA14-1 with this Bcl-2 surface pocket that is essential for Bcl-2 biological function. HA14-1 effectively induced apoptosis of human acute myeloid leukemia (HL-60) cells overexpressing Bcl-2 protein that was associated with the decrease in mitochondrial membrane potential and activation of caspase-9 followed by caspase-3. Cytokine response modifier A, a potent inhibitor of Fas-mediated apoptosis, did not block apoptosis induced by HA14-1. Whereas HA14-1 strongly induced the death of NIH 3T3 (Apaf-1(+/+)) cells, it had little apoptotic effect on Apaf-1-deficient (Apaf-1(-/-)) mouse embryonic fibroblast cells. These data are consistent with a mechanism by which HA14-1 induces the activation of Apaf-1 and caspases, possibly by binding to Bcl-2 protein and inhibiting its function. The discovery of this cell-permeable molecule provides a chemical probe to study Bcl-2-regulated apoptotic pathways in vivo and could lead to the development of new therapeutic agents.

Animals↗
PubMed2000

Internal morphology of human cervical pedicles.

STUDY DESIGN: The internal architecture of cervical spine pedicles was investigated by thin sectioning and digitization of radiographic images. OBJECTIVES: To provide quantitative information on the internal dimensions and cortical shell thicknesses of the middle and lower cervical pedicles. SUMMARY OF BACKGROUND DATA: Although there have been a number of studies presenting data on the external dimensions of the cervical pedicle, little is known regarding its internal architecture and cortical shell thickness along the pedicle axis. METHODS: Twenty-five human cervical vertebrae (C3-C7) were secured to a thin-sectioning machine to produce three 0.7-mm-thick pedicle slices along its axis. Plain radiographs of the pedicle slices were scanned and digitized to facilitate measurement of the internal dimensions. Computer software was specifically developed to determine the external dimensions (i.e., pedicle height and width) and the internal dimensions (i.e., cortical shell thicknesses of the superior, inferior, lateral, and medial walls and the cancellous core height and width) of cervical pedicles. RESULTS: Superior and inferior wall cortical thicknesses of pedicle thin slices were similar, whereas the lateral wall cortical thickness was significantly smaller than the medial wall thickness. The medial cortical shell (average value range: 1.2-2.0 mm) was measured to be 1.4 to 3.6 times as thick as the lateral cortical shell (average value range: 0.4-1.1 mm). When medial and lateral cortical thicknesses were normalized for external dimensions, the combined cortical shell thickness was thinnest at C7 (average value range: 18. 6-25.6% of the external width), and this result was statistically significant when compared with other vertebral levels. CONCLUSIONS: The cervical pedicle is a complex, three-dimensional structure exhibiting extensive variability in internal morphology. Characteristics of the cervical pedicle at different spinal levels must be noted before transpedicular screw fixation.

Bone Screws↗
PubMed2000

Galectin-3 expression and subcellular localization in senescent human fibroblasts.

Galectin-3 is a galactose/lactose-binding protein (M(r) approximately 30,000), identified as a required factor in the splicing of pre-mRNA. In the LG1 strain of human diploid fibroblasts, galectin-3 could be found in both the nucleus and the cytoplasm of young, proliferating cells. In contrast, the protein was predominantly cytoplasmic in senescent LG1 cells that have lost replicative competence through in vitro culture. Incubation of young cells with leptomycin B, a drug that disrupts the interaction between the leucine-rich nuclear export signal and its receptor, resulted in the accumulation of galectin-3 inside the nucleus. In senescent cells, galectin-3 staining remained cytoplasmic even in the presence of the drug, thus suggesting that the observed localization in the cytoplasm was due to a lack of nuclear import. In heterodikaryons derived from fusion of young and senescent LG1 cells, the predominant phenotype was galectin-3 in both nuclei. These results suggest that senescent LG1 cells might lack a factor(s) specifically required for galectin-3 nuclear import.

Antigens, Differentiation↗
PubMed2000

Cell permeable Bcl-2 binding peptides: a chemical approach to apoptosis induction in tumor cells.

Bcl-2 is a potent suppressor of apoptosis, and its overexpression contributes to tumorigenesis in many types of human cancers. To test the possibility of modulating Bcl-2 function as an anticancer strategy, a cell permeable Bcl-2 binding peptide, cell permeable moiety (cpm)-1285, was designed by chemically attaching a fatty acid to a peptide derived from the proapoptotic protein Bad. cpm-1285 entered HL-60 tumor cells, bound Bcl-2 protein, and induced apoptosis in vitro. In contrast, cpm-1285 had little effect on normal human peripheral blood lymphocytes. Furthermore, cpm-1285 had in vivo activity in slowing human myeloid leukemia growth in severe combined immunodeficient mice. These results demonstrate a novel approach for therapeutic intervention of tumor growth in vivo with small molecule inhibitors of Bcl-2.

Amino Acid Sequence↗
PubMed2000

Viscoelastic finite-element analysis of a lumbar motion segment in combined compression and sagittal flexion. Effect of loading rate.

STUDY DESIGN: A study using a validated viscoelastic finite-element model of a L2-L3 motion segment to identify the load sharing among the passive elements at different loading rates. OBJECTIVE: To enhance understanding concerning the role of the loading rate (i.e., speed of lifting and lowering during manual material handling tasks) on the load sharing and safety margin of spinal structures. SUMMARY OF BACKGROUND DATA: Industrial epidemiologic studies have shown that jobs requiring a higher speed of trunk motion contribute to a higher risk of industrial low back disorders. Consideration of the dynamic loading characteristics, such as lifting at different speeds, requires modeling of the viscoelastic behavior of passive tissues. Detailed systematic analysis of loading rate effects has been lacking in the literature. METHODS: Complex flexion movement was simulated by applying compression and shear loads at the top of the upper vertebra while its sagittal flexion angle was prescribed without constraining any translations. The lower vertebra was fixed at the bottom. The load reached its maximum values of 2000 N compression and 200 N anterior shear while L2 was flexed to 10 degrees of flexion in the three different durations of 0.3, 1, and 3 seconds to represent fast, medium, and slow movements, respectively. The resisted bending moment, gross load-displacement response of the motion segment, forces in facet joints and ligaments, stresses and strains in anulus fibrosus, and intradiscal pressure were compared across different rates. RESULTS: The distribution of stress and strain was markedly affected by the loading rate. The higher loading rate increased the peak intradiscal pressure (12.4%), bending moment (20.7%), total ligament forces (11.4%), posterior longitudinal ligament stress (15.7%), and anulus fiber stress at the posterolateral innermost region (17.9%), despite the 15.4% reduction in their strain. CONCLUSIONS: Consideration of the time-dependent material properties of passive elements is essential to improving understanding of motion segment responses to dynamic loading conditions. Higher loading rate markedly reduces the safety margin of passive spinal elements. When the dynamic tolerance limits of tissues are available, the results provide bases for the guidelines of safe dynamic activities in clinics or industry.

Elasticity↗
PubMed2000

Gamma-irradiation induces matrix metalloproteinase II expression in a p53-dependent manner.

Matrix metalloproteinases (MMPs) are a family of proteinases that degrade the basement membrane and have been implicated in promoting tumor metastasis. MMP-2, one member of this family, was recently found to be a p53 target and subject to p53 upregulation. In this study, we examined the correlation between the expression of MMP-2 and the increased expression of p53 after gamma-irradiation. Three human p53-positive cell lines that express wild-type p53, including U2-OS (osteosarcoma), RKO (colon carcinoma), MCF-7 (breast carcinoma), one mouse p53 positive cell line and HepG2 (liver carcinoma), and two p53-negative human cell lines, SAOS-2 (osteosarcoma) and RKO-E6 (colon carcinoma), were used in this study. The MMP-2 activity was analyzed by using gelatin zymography. The p53 level was measured by western blot analysis. Our results show that wild-type p53 induced by ionizing radiation caused a subsequent increase of MMP-2 activity in U2-OS and RKO cells but not in MCF-7, HepG2, SAOS-2, or RKO-E6 cells. These results suggest that the gamma-radiation-induced expression of MMP-2 is dependent on the cell type and presence of functional p53. Thus, ionizing radiation could activate MMP-2 activity in a subset of human cancer cells and may lead to an increase in their metastatic potential.

Animals↗
PubMed2000

Anatomical subdivisions of the stomach of the Bactrian camel (Camelus bactrianus).

Twenty stomachs of Bactrian camels (Camelus bactrianus) were studied by gross dissection. Based on the configuration of the stomach and the structure of the mucous membrane, the stomach was divided into three ventricles that differ from the arrangement described for ox and sheep. The first and second ventricles of the proventriculus of camel form one stomach rather than two different stomachs. These ventricles of the proventriculus do not correspond to the rumen and reticulum of ox and sheep. The third ventricle appears to be the abomasum. One part of the abomasum has reticular mucosal folds that indicate it is not the reticulum. A second part of the abomasum has longitudinal mucosal folds suggesting it is not the omasum. Three glandular sac areas associated with the preventriculus and abomasum are also described.

Abomasum↗
PubMed2000

Dual action of palmitoyl trifluoromethyl ketone (PACOCF3) on Ca2+ signaling: activation of extracellular Ca2+ influx and alteration of ATP- and bradykinin-induced Ca2+ responses in Madin Darby canine kidney cells.

The effect of the phospholipase A2 inhibitor palmitoyl trifluoromethyl ketone (PACOCF3) on Ca2+ signaling in Madin Darby canine kidney (MDCK) cells was examined using fura-2 as the fluorescent Ca2+ indicator. At a concentration of 20 microM, PACOCF3 did not change basal cytosolic free calcium concentrations ([Ca2+]i), but at concentrations of 50-250 microM PACOCF3 induced an increase in [Ca2+]i by activating extracellular Ca2+ entry which was partly suppressed by 50 microM La3+. The effect of PACOCF3 was abolished by removal of extracellular Ca2+. PACOCF3 (10 microM) enhanced both the peak value and the area under the curve of the [Ca2+]i increase induced by 10 microM ATP and 1 microM bradykinin by potentiating extracellular Ca2+ influx without affecting internal Ca2+ release. Several other phospholipase A2 inhibitors had no effect on basal [Ca2+]i or agonist-induced [Ca2+]i increases. Collectively, the results suggest that PACOCF3 alters Ca2+ signaling in renal tubular cells in a manner independent of phospholipase A2 inhibition.

Adenosine Triphosphate↗
PubMed2000

The anatomic variability of human cervical pedicles: considerations for transpedicular screw fixation in the middle and lower cervical spine.

Transpedicular screw fixation has recently been shown to be successful in stabilizing the middle and lower cervical spine. Controversy exists, however, over its efficacy, due to the smaller size of cervical pedicles and the proximity of significant neurovascular structures to both lateral and medial cortical walls. To aid the spinal surgeon in the insertion of pedicle screws, a number of studies have been performed to quantify the gross dimensions and angulations of the cervical pedicle. Notwithstanding these quantitative studies, there has been a conspicuous absence of research reporting the qualitative characteristics of the cervical pedicle. The purpose of our study was to provide comparative graphical data that would systematically document the anatomic variability in cervical pedicle morphology. Such information should better elucidate the complexity of the pedicle as a three-dimensional structure and provide the spinal surgeon with a more complete understanding of cervical pedicle architecture. Twenty-six human cervical vertebrae (C3-C7) from six fresh-frozen spines were secured to a thin sectioning apparatus to produce three 0.7-mm-thick pedicle slices along its axis. Radiographs taken of these pedicle slices were scanned, digitized, and traced to facilitate visual comparison. The pedicle slices were found to exhibit substantial variability in composition and shape, not only between individual spines and vertebral levels, but also within the pedicle axis. However, the lateral cortex was consistently found to be thinner than the medial cortex in all samples. These physical findings must be noted by surgeons attempting transpedicular screw fixation in the cervical spine.

Bone Screws↗
PubMed2000

Negative association between T102C polymorphism at the 5-HT2A receptor gene and bipolar affective disorders in Singaporean Chinese.

BACKGROUND: Serotonergic system abnormalities have been implicated in the pathogenesis of bipolar affective disorders. The 5-hydroxytryptamine type 2A (5HTR2A) receptor gene located on chromosome 13 (13q14-21) can be considered as a candidate gene for bipolar affective disorder (BPAD). METHODS: Seventy-two patients with BPAD and 74 normal population controls were genotyped with restriction fragment length polymorphism (RFLP) in the 5HTR2A receptor gene. RESULTS: We report a negative association between 5HTR2A receptor gene and BPAD. The association was examined using a case-control design. Allele and genotype frequencies as well as homozygote-heterozygote distribution at the 5HTR2A receptor gene polymorphism were compared between the two groups. There were no significant differences in the allelic or genotype frequencies and the homozygote-heterozygote distributions. LIMITATIONS: Patients were recruited from one hospital in Singapore. The case-control study design needs replication. CONCLUSION: Our finding indicates that the 5HTR2A receptor gene polymorphism is not a major factor in the genetic susceptibility to BPAD in Singaporean Chinese.

Adult↗
PubMed2000

NPC-14686, a novel anti-inflammatory agent, increased intracellular Ca(2+) concentrations in MDCK renal tubular cells.

The effect of NPC-14686 (Fmoc-L-homophenylalanine), a novel anti-inflammatory agent on intracellular free Ca(2+) concentrations ([Ca(2+)](i)) in Madin Darby canine kidney (MDCK) renal tubular cells, was investigated, using fura-2 as a Ca(2+) dye. At concentrations between 10 and 200 microM NPC-14686 increased [Ca(2+)](i) concentration dependently. The [Ca(2+)](i) signal comprised an initial rise and a sustained phase. Ca(2+) removal inhibited the Ca(2+) signals by 90%. In Ca(2+)-free medium, pretreatment with 100 microM NPC-14686 nearly abolished the [Ca(2+)](i) increase induced by 1 microM thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor) and abolished the [Ca(2+)](i) increase induced by 2 microM carbonylcyanide m-chlorophenylhydrazone (CCCP) (a mitochondrial uncoupler). NPC-14686 (100 microM) induced a slight [Ca(2+)](i) increase after pretreatment with 2 microM CCCP and 1 microM thapsigargin. Addition of 3 mM Ca(2+) elicited a [Ca(2+)](i) increase in cells pretreated with 100 microM NPC-14686 in Ca(2+)-free medium. Inhibition of inositol-1,4,5-trisphosphate (IP(3)) production by suppressing phospholipase C with 2 microM U73122 did not alter NPC-14686-induced Ca(2+) release. Trypan blue exclusion revealed that incubation with 10 or 200 microM NPC-14686 for 1-30 min decreased cell viability by 10-20% concentration dependently. Collectively, the results demonstrate that, in MDCK tubular cells, NPC-14686 induced Ca(2+) release followed by Ca(2+) entry, with the latter playing a major role. NPC-14686 appears to release intracellular Ca(2+) in an IP(3)-uncoupled manner. NPC-14686 may be of mild cytotoxicity.

Aminobutyrates↗
PubMed2000

Resurfacing deep wound of upper extremities with pedicled groin flaps.

A total of 29 axial pedicled groin skin flaps were applied clinically with satisfactory result excepting for one flap which tailed on transplantation. These cases included severe scar contracture of the dorsum of hands in 20 patients, deeply burned wounds with infection and exposure of deep structure in upper extremities in nine patients, such as electrical burns and hot-crushing injuries. The flap is supplied by two groups of nutrient vessels with abundant vascularization and located in a hidden area. Therefore, the pedicled groin skin flap is still valuable due to its advantages as safe, easy operation and strong antiinfective ability although the free groin flap is more widely used today.

Adult↗
PubMed2000

The arterial supply of the cubital joint in the Bactrian camel (Camelus bactrianus).

The arterial supply of the six cubital joints from bactrian camels was studied. There were 15 arterial branches supplying the joint. The branches that arose from the transverse cubital artery were the medial anterior, superior anterior, lateral anterior, middle anterior, inferior anterior, superior lateral, middle lateral, inferior lateral, superior posterior and superior lateral posterior cubital branches. The branches originating from the collateral ulnar artery were the medial, middle posterior, inferior posterior, medial posterior and inferior lateral posterior cubital branches. These arteries united with each other around the cubital joint.

Animals↗
PubMed2000

The arterial supply of the carpal joint in the Bactrian camel (Camelus bactrianus).

The arterial supply of the six carpal joints was studied in Bactrian camels. The arterial branches supplying the carpal joints were the proximal medial dorsal, middle medial dorsal, distal medial dorsal, proximal lateral dorsal, distal lateral dorsal, proximal medial palmar, distal medial palmar, lateral palmar, proximal palmar and dorsal palmar carpi and the dorsal interosseous antebrachium branches. Some small unnamed branches supplied the diverticulum and the antebrachiocarpal joint capsule. All these arteries arose from the lateral and medial branches of the radial artery.

Animals↗
PubMed2000

A change-point model for reporting delays under change of AIDS case definition.

Accurate monitoring of disease incidence is of major public health concern. The time delay between diagnosis and the date of reporting creates bias in estimating disease incidence. Changes in case definition are expected to have an impact on the time lag of case reporting. We propose a change-point model for reporting delays in AIDS that takes into account recent changes in the AIDS definition in US and European countries. The model was applied to California AIDS surveillance data and the distribution of reporting delays before and after the recent change of definition in 1993 were analyzed in terms of contributing factors. The overall significance of the model with change-point as compared to the model without change-point indicates that the effect of the 1993 change in definition on the distribution of reporting delays was highly significant (p < 0.0001). Overall, reporting delay of cases initially diagnosed with AIDS-defining diseases before 1993 was shorter compared to after 1993; reporting delay of cases initially diagnosed meeting the 1993 immunologic case definition was shorter than of those initially diagnosed with AIDS-defining diseases. Region of residence, mode of exposure, race/ethnicity and time of diagnosis emerged as the main covariates in the models. The method introduced here applies to current and possible future changes of the AIDS case definition as well as changes in diagnostic criteria or case definition in diseases other than AIDS. We demonstrate that such changes may be accompanied by sizeable changes in the distribution of reporting delays, and thus adjustment for reporting delays must be recalibrated after a change in definition.

Acquired Immunodeficiency Syndrome↗
PubMed2000

The arterial supply to the digits of the forelimb in the Bactrian camel (Camelus bactrianus).

The arterial supply of the digits of the forelimb of the Bactrian camel is described. The arteries supplying the digits were the palmar metacarpal and common palmar digital arteries III. The palmar metacarpal artery III was the continuation of the deep medial proximal metacarpal branch which was derived from the medial branch of the radial artery. It gave rise to a nutrient branch, medial branch, lateral branch and distal perforating palmar branch at the proximal end of the distal sixth of the cannon bone (fused third and fourth metacarpal bones). The common palmar digital artery III was the continuation of the median artery, which divided into medial and lateral branches. The medial branch of common palmar digital artery III which occasionally arose from the axial palmar proper digital artery III, after giving rise to the axial proximal proximal phalangeal branch, divided into the axial and abaxial palmar proper digital arteries III. The axial palmar proper digital artery III gave off the dorsoaxial distal proximal phalangeal, dorsoaxial proximal middle phalangeal, dorsoaxial distal middle phalangeal, palmoaxial middle phalangeal, palmoaxial distal phalangeal, dorsoaxial distal phalangeal branches, coronal artery and some digital tori branches. The abaxial palmar proper digital artery III gave rise to the abaxial proximal proximal phalangeal, dorsoabaxial distal proximal phalangeal, dorsoabaxial middle phalangeal, palmoabaxial middle phalangeal, palmoabaxial distal phalangeal, dorsoabaxial distal phalangeal branches, coronal artery and some digital tori branches. The lateral branch of the common palmar digital artery III in its origin, course, branching pattern and supply in the fourth digit was similar to the medial branch of common palmar digital artery III in the third digit.

Adaptation, Physiological↗
PubMed2000

A selective cyclooxygenase-2 inhibitor decreases proteinuria and retards progressive renal injury in rats.

BACKGROUND: We have previously shown that cyclooxygenase-2 (COX-2) expression is low in the renal cortex of adult rats, but is increased in macula densa/cortical thick ascending limb and in glomerular podocytes after subtotal renal ablation. METHODS: To evaluate the functional consequences of this increased COX-2 expression, male rats were subjected to subtotal renal ablation and divided into four groups: (1) treatment with the selective COX-2 inhibitor SC58236, (2) treatment with vehicle, (3) treatment with the angiotensin-converting enzyme inhibitor enalapril, and (4) treatment with enalapril + SC58236. The administration of drugs was begun on the third day after ablation and continued for 6 to 10 weeks. RESULTS: Within one week after ablation, vehicle-treated rats developed hypertension. Although enalapril led to significant reductions in blood pressure, either alone or in combination with the COX-2 inhibitor, SC58236 alone did not significantly alter ablation-induced hypertension. However, the SC58236-treated animals exhibited levels of proteinuria at six weeks after ablation that were comparable to those seen with enalapril (vehicle, 47 +/- 4; enalapril, 27 +/- 2; SC58236, 30 +/- 2 mg/day; N = 7, P < 0.01, each group compared with vehicle), and continued SC58236 treatment led to persistent reductions in proteinuria at 10 weeks after renal ablation (vehicle, 77 +/- 4; SC58236, 50 +/- 4 mg/day; N = 6, P < 0. 01). SC58236 treatment also significantly reduced the percentage of glomeruli exhibiting segmental or global sclerosis at 10 weeks (32.6 +/- 7.8% vs. 10.9 +/- 2.8%, N = 6, P < 0.03). Furthermore, SC58236 treatment partially inhibited increases in transforming growth factor-beta1 mRNA expression and increases in collagen III and collagen IV mRNA expression. CONCLUSIONS: These studies indicate that chronic treatment with a specific COX-2 inhibitor may retard the progression of progressive renal injury, and suggest that such compounds can be used in combination with angiotensin-converting enzyme inhibitors. Further studies are required to determine the mechanism by which COX-2 inhibition is renoprotective.

Angiotensin-Converting Enzyme Inhibitors↗