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Biomedical subjects

S Teng

Publications and source records attributed to S Teng.

At least 19 recordsLinked to original sources
PubMed2001

Cytochrome P450 2E1 metabolically activates propargyl alcohol: propiolaldehyde-induced hepatocyte cytotoxicity.

Pargyline, an antihypertensive agent and monoamine oxidase inhibitor, induces hepatic GSH depletion and hepatotoxicity in vivo in rats [E.G. De Master, H.W. Sumner, E. Kaplan, F. N. Shirota, H.T. Nagasawa, Toxicol. Appl. Pharmacol. 65 (1982) 390-401]. Propargyl alcohol (2-propyn-1-ol), because of its structural similarity to allyl alcohol, was thought to be activated by alcohol dehydrogenase. However, it is a poor substrate compared to allyl alcohol and it was therefore proposed that propargyl alcohol-induced liver injury involved metabolic activation by catalase/H(2)O(2) [E.G. De Master, T. Dahlseid, B. Redfern, Chem. Res. Toxicol. 7 (1994) 414-419]. In the following we showed that; (1) propargyl alcohol-induced cytotoxicity was markedly enhanced in CYP 2E1-induced hepatocytes and prevented by various CYP 2E1 inhibitors but was only slightly affected when alcohol dehydrogenase was inhibited with methylpyrazole/DMSO or when catalase was inactivated with azide or aminotriazole, (2) hepatocyte GSH depletion preceded cytotoxicity and was inhibited by cytochrome P450 inhibitors but not by catalase/alcohol dehydrogenase inhibitors. GSH conjugate formation during propargyl alcohol metabolism by microsomal mixed function oxidase in the presence of GSH was also prevented by anti-rat CYP 2E1 or CYP 2E1 inhibitors, (3) cytotoxicity was prevented when lipid peroxidation was inhibited with antioxidants, desferoxamine (ferric chelator) or dithiothreitol. Propargyl alcohol-induced cytotoxicity and reactive oxygen species formation were markedly increased in GSH-depleted hepatocytes. All of this evidence suggests that propargyl alcohol-induced cytotoxicity involves metabolic activation by CYP 2E1 to form propiolaldehyde that causes hepatocyte lysis as a result of GSH depletion and lipid peroxidation.

Aldehydes↗
PubMed2001

The formaldehyde metabolic detoxification enzyme systems and molecular cytotoxic mechanism in isolated rat hepatocytes.

The toxicity and carcinogenicity of formaldehyde (HCHO) has been attributed to its ability to form adducts with DNA and proteins. A marked decrease in mitochondrial membrane potential and inhibition of mitochondrial respiration that was accompanied by reactive oxygen species formation occurred when isolated rat hepatocytes were incubated with low concentrations of HCHO in a dose-dependent manner. Hepatocyte GSH was also depleted by HCHO in a dose-dependent manner. At higher HCHO concentrations, lipid peroxidation ensued followed by cell death. Cytotoxicity studies were conducted in which isolated hepatocytes exposed to HCHO were treated with inhibitors of HCHO metabolising enzymes. There was a marked increase in HCHO cytotoxicity when either alcohol dehydrogenase or aldehyde dehydrogenase was inhibited. Inhibition of GSH-dependent HCHO dehydrogenase activity by prior depletion of GSH markedly increased hepatocyte susceptibility to HCHO. In each case, cytotoxicity was dose-dependent and corresponded with a decrease in hepatocyte HCHO metabolism and increased lipid peroxidation. Antioxidants and iron chelators protected against HCHO cytotoxicity. Cytotoxicity was also prevented, when cyclosporine or carnitine was added to prevent the opening of the mitochondrial permeability transition pore which further suggests that HCHO targets the mitochondria. Thus, HCHO-metabolising gene polymorphisms would be expected to have toxicological consequences on an individual's susceptibility to HCHO toxicity and carcinogenesis.

Alcohol Dehydrogenase↗
PubMed2001

v-Src transformation is mediated through farnesylated proteins.

Src is an oncoprotein which has been implicated in a number of human malignancies in which it has been shown to be overexpressed and highly activated. The precise mechanism of Src transformation, however, is still poorly understood. We hypothesized that Ras and other farnesylated proteins may mediate Src transformation. To test this hypothesis, v-Src-transfected rat fibroblasts (3Y1) were treated every 72 h with a 15 microM concentration of a farnesyl-transferase inhibitor (FTI). At 2 weeks, a focus formation assay was performed to assess transformation potential. Untreated and FTI-treated v-Src-transfected 3Y1 cells formed a mean of 39 (+/-2.6) and 29.8 (+/-2.9) foci per well, respectively. This 24% decrease was judged to be statistically significant (P = 0.02). Moreover, foci (>90%) in the FTI-treated wells were also consistently smaller than foci in the untreated wells. Western blots with antibody directed toward H-Ras confirmed complete inhibition of Ras farnesylation in the treated cell lines. The specificity of this inhibition was verified by Western blot using antibody specific for Rap1A. The transforming potential of v-Src is inhibited, but not eliminated by FTI treatment. This suggests that v-Src transformation is mediated in part by farnesylated proteins, one of which may be Ras.

Alkyl and Aryl Transferases↗
PubMed2001

[QTLs analysis of tiller angle in rice (Oryza sativa L.)].

Tiller angle is one of important characters that constitute plant type with great significance in breading. A pair of japonica/indica lines, which were significantly different in tiller angle, were used in this study. A DH population were constructed via anther culture of F1 hybrids. The tiller angles of 115 DH lines were measured. QTL analysis was conducted based on the constructed molecular linkage map. Three QTLs (qTA-9a, qTA-9b and qTA-12) were detected on chromosome 9 and 12 respectively, Their variation were 22.7%, 11.9% and 20.9% respectively and their additive effects were all negative, showing this character was controlled by genes from big tiller angle parent ZYQ8. The application of the tiller angle that was controlled by major genes and minor genes in rice breeding is also discussed.

Chromosome Mapping↗
PubMed2000

Strain in the braincase and its sutures during function.

The skull is distinguished from other parts of the skeleton by its composite construction. The sutures between bony elements provide for interstitial growth of the cranium, but at the same time they alter the transmission of stress and strain through the skull. Strain gages were bonded to the frontal and parietal bones of miniature pigs and across the interfrontal, interparietal and coronal sutures. Strains were recorded 1) during natural mastication in conjunction with electromyographic activity from the jaw muscles and 2) during stimulation of various cranial muscles in anesthetized animals. Vault sutures exhibited vastly higher strains than did the adjoining bones. Further, bone strain primarily reflected torsion of the braincase set up by asymmetrical muscle contraction; the tensile axis alternated between +45 degrees and -45 degrees depending on which diagonal masseter/temporalis pair was most active. However, suture strains were not related to overall torsion but instead were responses to local muscle actions. Only the coronal suture showed significant strain (tension) during jaw opening; this was caused by the contraction of neck muscles. All sutures showed strain during jaw closing, but polarity depended on the pattern of muscle usage. For example, masseter contraction tensed the coronal suture and the anterior part of the interfrontal suture, whereas the temporalis caused compression in these locations. Peak tensile strains were larger than peak compressive strains. Histology suggested that the skull is bent at the sutures, with the ectocranial surface tensed and the endocranial surface predominantly compressed. Collectively, these results indicate that skulls with patent sutures should be analyzed as complexes of independent parts rather than solid structures.

Animals↗
PubMed2000

Cancer chemoprevention and apoptosis mechanisms induced by dietary polyphenolics.

This review summarises current knowledge on the various molecular chemopreventive or therapeutic mechanisms that may be involved when the administration of flavonoids or polyphenols prevented chemical carcinogenesis in animal models. These mechanisms can be subdivided into the following: 1) the molecular mechanisms involved in preventing carcinogen metabolic activation, 2) the molecular mechanisms for preventing tumour cell proliferation by inactivation or downregulation of prooxidant enzymes or signal transduction enzymes, 3) the molecular cell death mechanisms for the induction of tumour cell death (apoptosis) and the molecular mechanisms for the inhibition of isolated mitochondria functions. Many of the flavonoids and polyphenols found in diets, supplements or herbal medicine were also ranked using "accelerated cytotoxic mechanism screening" by a combinatorial approach utilising isolated rat hepatocytes. A strong correlation of an early collapse of the mitochondrial membrane potential and cell death was found for most of the cytotoxic polyphenols but did not occur with non-toxic polyphenols. This screening could prove useful for eliminating polyphenols that have the potential for adverse health effects and for selecting safe and effective polyphenolic candidates for further development as supplements for preventing cancer or cardiovascular disease. Safety concerns of flavonoid/polyphenol supplements are also reviewed.

Animals↗
PubMed2000

Do cytokeratin-positive-only sentinel lymph nodes warrant complete axillary lymph node dissection in patients with invasive breast cancer?

The small number of nodes harvested with lymphatic mapping and sentinel lymph node (SLN) biopsy has allowed a more detailed pathologic examination of those nodes. Immunohistochemical stains for cytokeratin (CK-IHC) have been used in an attempt to minimize the false negative rate for SLN mapping. This study examines the value of CK-IHC positivity in predicting further lymph node involvement in the axillary basin. From April 1998 through May 1999, 519 lymphatic mappings and SLN biopsies were performed for invasive breast cancer. SLNs were examined by imprint cytology, hematoxylin and eosin (H&E), and CK-IHC. Patients with evidence of metastatic disease by any of the above techniques were eligible for complete axillary node dissection (CAND). The frequency with which these modalities predicted further lymph node involvement in the axillary basin was compared. Of the 519 lymphatic mappings, 39 patients (7.5%) had a CK-IHC-positive-only SLN. Five (12.8%) of these 39 patients had at least 2 SLNs positive by CK-IHC. Twenty-six of the CK-IHC-positive-only patients underwent CAND. Three of these 26 patients (11.5%) had additional metastases identified after CAND. The sensitivity levels with which each modality detected further axillary lymph node involvement were as follows: CK-IHC, 98 per cent; H&E, 94 per cent; and imprint cytology, 87 per cent. A logistic regression to compare the prognostic value of the three modalities was performed. All were significant, with odds ratios of 19.1 for CK-IHC (P = 0.015), 5.3 for H&E (P = 0.033), and 3.86 for imprint cytology (P = 0.0059). These data validate the enhanced detection of CK-IHC for the evaluation of SLNs. Detection of CK-IHC-positive SLNs appears to warrant CAND in patients with invasive breast cancer. However, the therapeutic value of CAND or adjuvant therapies based on CK-IHC-positive SLNs would be best answered by prospective randomized trials.

Breast Neoplasms↗
PubMed1999

In vivo gene expression profile analysis of human breast cancer progression.

The development and use of molecular-based therapy for breast cancer and other human malignancies will require a detailed molecular genetic analysis of patient tissues. The recent development of laser capture microdissection and high density cDNA arrays now provides a unique opportunity to generate gene expression profiles of cells from various stages of tumor progression as it occurs in the actual neoplastic tissue milieu. We report the combined use of laser capture microdissection and high-throughput cDNA microarrays to monitor in vivo gene expression levels in purified normal, invasive, and metastatic breast cell populations from a single patient. These in vivo gene expression profiles were verified by real-time quantitative PCR and immunohistochemistry. The combined use of laser capture microdissection and cDNA microarray analysis provides a powerful new approach to elucidate the in vivo molecular events surrounding the development and progression of breast cancer and is generally applicable to the study of malignancy.

Breast Neoplasms↗
PubMed1999

Surgical Approaches to Esophageal Cancer.

BACKGROUND: Esophageal cancer is a highly lethal malignancy. Esophageal resection remains the primary treatment in most centers. A number of approaches to esophageal resection have been described. METHODS: The authors review the current approaches to esophageal resection and adjuvant therapy for esophageal cancer. RESULTS: Transthoracic, transhiatal, and minimally invasive techniques are currently employed in esophageal surgery for malignancy. A number of authors favor extended mediastinal and cervical lymphadenectomy in hopes of improving survival. Combined chemotherapy and radiotherapy in the neoadjuvant setting appears to offer some promise. CONCLUSIONS: No consensus of opinion exists regarding the optimal approach or extent of esophageal resection for cancer. Prospective, randomized trials of neoadjuvant therapy may determine its efficacy. Newer approaches may enhance quality of life.

Journal Article↗
PubMed1999

[Reconstruction and repair after resection of soft tissue sarcoma].

OBJECTIVE: To emphasize the importance of reconstruction and repair after resection of soft tissue sarcoma. METHODS: From November 1990 to November 1996, in 107 cases of soft tissue sarcoma 32 cases had received various reconstructive or reparative operations. Among the 32 cases, 4 cases were primary sarcomas and 28 cases were recurrent sarcomas. In surgical grading, 3 cases were of I B, 3 cases of II A and 26 cases of II B. Radical resection was performed in 13 cases, widen local resection in 17 cases and local excision in 2 cases. After operation, 13 cases received chemotherapy and 7 cases received radiotherapy. Reconstruction of blood vessels was performed in 3 cases, reconstruction of kinetic function in 16 cases, and repair of defect was carried out in 23 cases. RESULTS: Thirty patients were followed up for 4 months to 6 years and 6 months. The clinical results showed that the local control rate of sarcoma was 80%, limb-salvage rate after reconstruction of blood vessels was 100%, the excellent and good rate after reconstruction of kinetic function was 87.5%, and the survival rate of the tissue flap of transplantation and transposition was 96%. CONCLUSION: It was concluded that the reconstruction and repair after resection of soft tissue sarcoma was the extension of operative treatment, and was very important in lowering the recurrence rate and improving the life quality of the sufferings.

Adolescent↗
PubMed1998

Compressive loading on bone surfaces from muscular contraction: an in vivo study in the miniature pig, Sus scrofa.

Several authors have speculated that muscles contracting adjacent to bony surfaces may cause compressive loads against the bone and thus influence skull development. This study was undertaken to evaluate the premise of this argument. A flat, semiconductor pressure transducer was surgically placed on bony surfaces beneath muscle attachments. Pressures were recorded during normal mastication (n = 7) and while overlying muscles were stimulated in anesthetized pigs (n = 15). The transducer was highly specific; no pressure was recorded in quiescent or passively stretched muscles or when other muscles were stimulated. Contraction of the overlying muscles exerted high normal loads on the bone, always exceeding systolic blood pressure (16 kPa). Temporal fossa pressure during mastication followed temporalis electromyographic (EMG) signals with a lag period approximating the twitch contraction time. When three different sites were compared in anesthetized animals, compressive load was highest on the temporal fossa (111.4 +/- 56.5 kPa, n = 15), intermediate on the mandibular angle (58.4 +/- 28.3 kPa, n = 4), and lowest on the medial side of the zygomatic arch (37.2 +/- 19.7 kPa, n = 15). Pressure amplitudes were not related to body size or relative muscle size. Muscle complexity and compartmental constraints did appear to influence pressure. Disruption of the external aponeurosis of the masseter decreased pressure on the mandibular angle by 45%, confirming the importance of tendinous constraint in determining pressure production. Thus, contracting muscles exert substantial but site-specific compressive loads on adjacent bone surfaces.

Animals↗
PubMed1997

The human immunodeficiency virus type 1 Tat protein potentiates zidovudine-induced cellular toxicity in transgenic mice.

3'-Azido-2',3'-dideoxythymidine (AZT, zidovudine) is the principal antiretroviral agent in the treatment of AIDS. Although beneficial, AZT remains restricted for human usage because of its severe toxic effects. We examined the AZT sensitivity in transgenic mice expressing HIV-1 one-exon-encoded 72 amino acid Tat (Tat72) and full-length 86 amino acid Tat (Tat86) proteins. Administration of AZT (1 mg/ml) in drinking water for 1 week resulted in a three- to fourfold decrease in hematopoietic progenitors from bone marrow in Tat mice compared to AZT-treated nontransgenic controls as determined by erythroid and granulocyte/macrophage colony-forming unit assays. In liver and thymus, two of the tissues examined, AZT treatment of Tat mice resulted in as much as 80-90% suppression of Mn-superoxide dismutase (Mn-SOD) activity. Other parameters associated with loss of Mn-SOD such as increase in carbonyl proteins and decrease of sulfhydryl content were also significantly enhanced by AZT in Tat mice. Our in vivo study suggests that AZT therapy is associated with oxidative damage affecting cellular functions in several tissues and that Tat is one of the contributory factors in AZT-induced toxicities. The findings of AZT-induced oxidative damage may help to improve the therapeutic index of AZT and other related drugs in AIDS patients.

Animals↗
PubMed1997

Stereological analysis of bone architecture in the pig zygomatic arch.

BACKGROUND: Stereological analysis of trabecular bone structure may reveal information about regional variations in stress distribution, especially in areas like the zygomatic arch in which those variations are difficult to assess mechanically. This study investigates regional differences in trabecular orientation, thickness, and density in the zygomatic and squamosal bones of pigs. METHODS: Zygomatic arches were serially sectioned frontally (n = 4), horizontally (n = 4), or parasagittally (n = 4), at a thickness of 0.8 mm. Sections were viewed under a stereomicroscope; video-images were digitized and analyzed with an automated program. RESULTS: All regions were anisotropic. Predominant orientation of trabeculae differed between and within bones. Three main patterns were seen. Anteriorly, zygomatic trabeculae were mainly arranged vertically and anteroposteriorly (relative to the occlusal plane). Posteriorly, including the jaw joint region, the squamosal featured primarily mediolateral trabeculae. In the midsection of the arch, where the two bones overlap, the trabeculae displayed a predominantly anteroposterior orientation with a secondary mediolateral peak. Trabeculae were typically 0.3-0.4 mm wide and occupied 40-50% of the area of the sections with few regional variations. CONCLUSIONS: Trabecular bone in the pig zygomatic arch is arranged orthogonally, relative to the occlusal plane. In conjunction with information from strain gauge recording, these data suggest that the zygomatic bone is bent in the parasagittal plane whereas the squamosal is bent out-of-plane. The mediolateral trabeculae in the posterior regions are consistent with a cantilever effect at the jaw joint.

Animals↗
PubMed1997

Rigid fixation and strain patterns in the pig zygomatic arch and suture.

PURPOSE: In orthognathic surgery, rigid fixation is routinely used to hold together bone fragments that may experience heavy force from attached masticatory muscles. Internal fixation plates are assumed to hold bony parts rigidly, but the mobility at such sites subjected to normal masticatory function has not been measured. The purpose of this study was to investigate in vivo the degree to which a linear plate immobilizes separated bones, specifically sutures. MATERIALS AND METHODS: Three female miniature pigs (Sus scrofa) had 1.3-mm Synthes titanium plates placed across the suture in the zygomatic arch. Foil strain gauges were used to record load deformation in the zygomatic and squamosal (temporal) bones and across the vertical and horizontal parts of the suture. Strain was recorded in vivo during mastication and in anesthetized pigs with electrical stimulation of masticatory muscles. RESULTS: Strain at the suture was not reduced from normal levels. The plate induced increases in strain within the bones, but the changes were slight. CONCLUSION: The results indicate that linear "rigid fixation" does not immobilize sutures.

Animals↗
PubMed1997

Reaction strains on the condylar neck during mastication and maximum muscle stimulation in different condylar positions: an experimental study in the miniature pig.

Most researchers agree that the primate temporomandibular joint (TMJ) is loaded compressively during function and that condylar position must play a role in mediating such loads. However, the precise nature of that role remains unclear. Using a pig model in this study, we attempted to analyze strain on the neck of the condyle during normal mastication and during simulated function in different condylar positions. Miniature three-element rosette strain gauges were bonded to the lateral surface of the condylar neck in 4 female miniature pigs (one per condyle). Measurements of strain were made during normal mastication and with the pigs under general anesthesia during maximum stimulation of the masseter and temporalis muscles in each of five condylar positions--centric occlusion, centric relation, anterior, relaxed and wide open--established through use of acrylic splints. Condylar position was evaluated by superimposition of lateral and dorsoventral cephalograms, with measurement of horizontal and vertical changes in location of implants placed on the zygomatic arch. As in primates, the TMJ was found to be load-bearing during mastication, with compressive strain oriented approximately perpendicular to the occlusal plane. In 3 pigs, strain was higher during balancing than during working function. During stimulation, the TMJ reaction strains were significantly lower with the condyles in the anterior position compared with the other positions, and the compressive strain was directed more anteriorly along the neck of the condyle in that position.

Analysis of Variance↗
PubMed1996

Patterns of bone strain in the zygomatic arch.

BACKGROUND: The transmission of force through the skull is complicated by the irregular form of the bones, the interposed sutures, and the multiplicity of loads from the teeth, muscles, and environment. The in vivo relationship between bone strain and muscle function in the mammalian skull is best investigated empirically. METHODS: We studied the zygomatic arch of pigs (Sus scrofa) by simultaneous strain gauge recording and electromyography. Seventeen juvenile animals were used, employing multiple strain gauges arranged either in rosettes or strips. Strain was recorded during mastication and muscle stimulations. Bony architecture was examined on sectioned specimens. RESULTS: Strain patterns were complex even in this beamlike structure. During masseteric contraction, the more anterior zygomatic bone showed in-plane bending such that its lower border became more convex, and the major principal strain axis (tension) was parallel to the masseter muscle. The posterior squamosal bone was slightly bent in the opposite direction, and the major principal strain was rotated 45-60 degrees from the masseteric line of action. Strain magnitudes in the squamosal were larger than those in the zygomatic. Woven bone composing the surface of the arch appeared denser in the zygomatic bone, where its predominant orientation corresponded with compressive strain. In the squamosal bone trabeculae were more regularly arranged, but their orientation did not correspond with strain axes. CONCLUSIONS: The magnitude differences are probably related to the different architecture of the zygomatic and squamosal bones, whereas the different strain patterns primarily reflect the influence of the sutures in selectively damping or transmitting loads. In particular, the zygomatic bone may be loaded by three-point, distributed-load bending, whereas the squamosal, loaded at only two points, may be sheared. We conclude that each cranial bone functions in a unique strain environment, with the sutures serving to redirect loading.

Animals↗
PubMed1996

Anatomic and directional variation in the mechanical properties of the mandibular condyle in pigs.

Stereologic studies of trabecular architecture suggest that the pig mandibular condyle is strongest when loaded supero-inferiorly, and that stress is concentrated in the antero-inferior region (Teng and Herring, 1995). To test these hypotheses, we investigated the uni-axial mechanical properties of 22 pig mandibular condyles in three loading directions at a mean strain rate of 0.14 (+/- 0.12)% s-1. A total of 91 rectangular beam specimens (averaging 9.0 mm x 6.0 mm x 5.0 mm) was tested. For each specimen, 5 or 6 non-destructive tests were performed before compressive failure. Strain in both longitudinal and transverse directions was measured by foil strain gauges on the central part of the specimen. Data were normalized at a strain rate of 0.1% s-1, specimen length of 9 mm, and cross-sectional area of 30.25 mm2. Generally, modulus of elasticity (E) and ultimate stress (sigma u) in the anterior regions of the condyle were greater than those in the posterior. E, sigma u, and Poisson's ratio (upsilon) were significantly different among the test directions, but ultimate strain (epsilon u) was not. The highest values of E (4.04 GPa), sigma u (14.97 MPa), and rho (0.81 g/cm3) were seen in the anterior inferior/middle region under supero-inferior loading. The lowest values (0.94 GPa for E, 2.38 MPa for sigma u, and 0.52 g/cm3 for rho) were found in the inferior/posterior region in medio-lateral loading. Although the mechanical properties of the condyle vary depending upon location, these results verify that the condyle is strongest and stiffest under compressive loads in the supero-inferior direction, and that the anterior-inferior region is particularly strong and stiff.

Analysis of Variance↗