Biomedical subjects

F Zhang

Publications and source records attributed to F Zhang.

At least 289 records · Page 16Linked to original sources

PubMed1999

Curcumin inhibits cyclooxygenase-2 transcription in bile acid- and phorbol ester-treated human gastrointestinal epithelial cells.

We investigated whether curcumin, a chemopreventive agent, inhibited chenodeoxycholate (CD)- or phorbol ester (PMA)-mediated induction of cyclooxygenase-2 (COX-2) in several gastrointestinal cell lines (SK-GT-4, SCC450, IEC-18 and HCA-7). Treatment with curcumin suppressed CD- and PMA-mediated induction of COX-2 protein and synthesis of prostaglandin E2. Curcumin also suppressed the induction of COX-2 mRNA by CD and PMA. Nuclear run-offs revealed increased rates of COX-2 transcription after treatment with CD or PMA and these effects were inhibited by curcumin. Treatment with CD or PMA increased binding of AP-1 to DNA. This effect was also blocked by curcumin. In addition to the above effects on gene expression, we found that curcumin directly inhibited the activity of COX-2. These data provide new insights into the anticancer properties of curcumin.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1999

Prolonged perivascular use of verapamil or lidocaine decreases skin flap necrosis.

During this experiment the authors investigated whether prolonged local use of verapamil or lidocaine prevents vasoconstriction and establishes better blood supply to the rat epigastric skin flap, hence reducing the necrosis that occurs otherwise. Abdominal wall skin flaps of 45 Sprague-Dawley rats, based on a single pedicle of the femoral vessels, were elevated. A subcutaneous pocket for the microport valve was created, and the adjacent catheter tip was sewn next to the femoral vessels. In the control and the two treatment groups, 0.5 ml saline or vasodilator solution respectively was injected through the microport every 12 hours for 5 days. On postoperative day 5 there was no statistical difference between the flap surfaces in all groups. The area of flap necrosis was significantly lower in the verapamil- (p = 0.001) and the lidocaine-treated (p = 0.012) groups vs. the control group as determined by analysis of variance with Bonferroni's post hoc test. In conclusion, topical application of verapamil and lidocaine solutions for 5 postoperative days decreased flap marginal necrosis significantly. Prolonged injection of vasodilators in the vicinity of the vascular pedicle prevents vasospasm and improves blood supply to the flap.

Administration, Topical↗

PubMed1999

Saphenous neurocutaneous island flap model in the rat: evaluation of vascular supply.

Neurocutaneous flaps are utilized routinely in reconstructive surgery and even more so during the past decade. In this study, the vascular supply of the neurocutaneous flap in the rat model is presented and evaluated. Thirty-six flaps (3.5x3 cm2) were dissected on the medial aspect of the leg based on a pedicle of the saphenous nerve, saphenous artery, great saphenous vein, and the surrounding fascial tissues. Animals in the experiment were divided into five groups with different circulatory patterns of pedicle dissections. In group I (N = 12), the pedicle artery, vein, nerve, and fascia were preserved. In group II (neurocutaneous flap model, N = 24), the saphenous artery was transected and the vein, nerve, and fascia were preserved. In group III (intraneural vascular plexus circulation pattern, N = 12), the saphenous artery and the fascia were transected. In group IV (extraneural vascular plexus circulation pattern, N = 12), the saphenous artery and nerve were transected. In group V (N = 12), the entire pedicle was transected completely. Flap survival was evaluated grossly on postoperative day 7. All flaps survived in group I, but in group II 19 of 24 flaps survived completely, 3 of 24 had partial necrosis, and 2 of 24 were completely necrotic. Complete necrosis was observed in all group III flaps. In group IV, 6 of 12 flaps survived completely, 3 of 12 flaps survived partially, and 3 of 12 flaps were necrotic (p<0.05 vs. group I). Only one flap with partial necrosis survived in group V. In group II, the average survival area was not significantly different from group I (p>0.05). In conclusion, the saphenous neurocutaneous flap in the rat is a reliable microsurgical model. The saphenous neurocutaneous flap is commonly supplied by both the intraneural and extraneural vascular plexus, and although the latter is more important, neither provides sufficient vascular supply on its own.

Animals↗

PubMed1999

Inhibition of cyclooxygenase-2 expression. An approach to preventing head and neck cancer.

Cyclooxygenase (COX) catalyzes the formation of prostaglandins (PG) from arachidonic acid. A large body of evidence has accumulated to suggest that COX-2, the inducible form of COX, is important in carcinogenesis. In this study, we determined whether (1) COX-2 was overexpressed in squamous cell carcinoma of the head and neck (HNSCC) and whether (2) retinoids, a class of chemopreventive agents, blocked epidermal growth factor (EGF)-mediated activation of COX-2 expression. Levels of COX-2 mRNA were determined in 15 cases of HNSCC and 10 cases of normal oral mucosa. Nearly a 100-fold increase in amounts of COX-2 mRNA was detected in HNSCC. By immunoblot analysis, COX-2 protein was detected in 6 of 6 cases of HNSCC but was undetectable in normal mucosa. Because retinoids protect against oral cavity cancer, we investigated whether retinoids could suppress EGF-mediated induction of COX-2 in cultured oral squamous carcinoma cells. Treatment with EGF led to increased levels of COX-2 mRNA, COX-2 protein, and synthesis of PG. These effects were suppressed by a variety of retinoids. Based on the results of this study, it will be important to establish whether newly developed selective COX-2 inhibitors are useful in preventing or treating HNSCC. Moreover, the anticancer properties of retinoids may be due, in part, to inhibition of COX-2 expression. Combining a retinoid with a selective COX-2 inhibitor may be more effective than either agent alone in preventing cancer of the upper aerodigestive tract.

Carcinoma, Squamous Cell↗

PubMed1999

Mechanisms of fluoroquinolone transport by human neutrophils.

Neutrophils accumulate ciprofloxacin and other fluoroquinolones, a process that enhances the killing of intracellular pathogens and could facilitate the delivery of these agents to infection sites by migrating neutrophils. The mechanisms by which transport occurs have not been characterized. In the present study, quiescent neutrophils transported ciprofloxacin with an observed K(m) of 167 microgram/ml (501 microM) and a maximum velocity of 25.2 ng/min/10(6) cells. When neutrophils were stimulated with phorbol myristate acetate (PMA), a second component of ciprofloxacin transport was induced. This pathway had an apparent K(m) of 9.76 microgram/ml (29.3 microM) and a maximum velocity of 59.3 ng/min/10(6) cells. Transport by both pathways was Na(+) independent. Ciprofloxacin transport by quiescent cells was relatively insensitive to pH and N-ethylmaleimide but was competitively inhibited by adenine (K(i) = 1.55 mM). Papaverine, a benzylisoquinoline known to inhibit nucleobase transport, also inhibited ciprofloxacin transport by quiescent cells. In contrast, transport by PMA-stimulated cells was enhanced at pH 8.2, inhibited at pH 6.2, and blocked by N-ethylmaleimide. Cationic and neutral amino acids and cystine competitively inhibited ciprofloxacin transport by PMA-stimulated neutrophils (K(i) = 158 microM for ornithine) but had little effect on quiescent cells. PMA-activated transport was not inhibited when the Na(+) in the medium was replaced with K(+) or Li(+), and the pattern of inhibition by cationic and neutral amino acids was similar. In summary, neutrophils continuously transport ciprofloxacin via a transport pathway shared by adenine. Activation by PMA induces a separate, higher-affinity transport pathway shared by a broad scope of amino acids. Neutrophils utilize one or both of these mechanisms to transport other fluoroquinolones.

Adenine↗

PubMed1999

Comparison of levels of human immunodeficiency virus type 1 RNA in plasma as measured by the NucliSens nucleic acid sequence-based amplification and Quantiplex branched-DNA assays.

This study compared levels of human immunodeficiency virus type 1 RNA in plasma as measured by the Quantiplex branched-DNA and NucliSens nucleic acid sequence-based amplification assays. RNA was detectable in 118 of 184 samples (64.13%) by the Quantiplex assay and in 171 of 184 samples (92.94%) by the NucliSens assay. Regression analysis indicated that a linear relationship existed between the two sets of values (P < 0.0001), although the Quantiplex and NucliSens values were significantly different (P < 0.001), with the NucliSens values being approximately 0.323 log higher. Spearman correlation analysis indicated that the overall changes in patient viral load patterns were highly correlative between the two assays: r = 0.912, P < 0.0001. The lower limits of sensitivity were determined to be approximately 100 copies/ml and 1,200 to 1,400 copies/ml for the NucliSens and Quantiplex assays, respectively.

DNA, Viral↗

PubMed1999

Induction of B-cell lymphoma in BALB/c nude mice with an ecotropic, B-tropic helper virus present in the murine AIDS virus stock.

The pathogenicities of the murine AIDS (MAIDS) virus complex (LP-BM5) and ecotropic helper virus (BM5eco) isolated from the complex to BALB/c nude mice were studied to elucidate the possible role of replication-competent helper virus in inducing the monoclonal outgrowth of lymphoid cells. Neither LP-BM5 nor BM5eco was pathogenic in adult BALB/c nude mice. However, B-cell lymphoma developed with a very high frequency when either virus was inoculated into newborn BALB/c nude (nu/nu) mice. The cells from the B-cell lymphoma were easily transplanted into nude mice. These results suggested that ecotropic helper virus in the MAIDS virus complex plays an important role in inducing the monoclonal outgrowth of lymphoid cells under immunodeficient conditions caused by defective virus.

Animals↗

PubMed1999

EMAP II: a modulator of neovascularization in the developing lung.

Neovascularization is a key regulatory process in fetal growth and development. Although factors promoting growth and development of the pulmonary vasculature have been investigated, nothing is known regarding the molecular mechanisms that may counteract these stimuli. Endothelial monocyte-activating polypeptide (EMAP) II has recently been identified as an antiangiogenic factor in tumor vascular development. We postulated that EMAP II is a putative negative modulator of lung vascular growth. EMAP II mRNA and protein decrease fivefold (P < 0.01) as the developing lungs in the fetal mouse progress from having poor vascularization (day 14) to having complete vascular development at term (day 18.5). EMAP II protein expression continues to remain low throughout postnatal life and into adulthood, with the exception of a surge that correlates with microvascular maturation. Furthermore, through the use of in situ hybridization and immunohistochemistry, EMAP II is localized throughout the lung, with significant expression in the submyoepithelial area during the early stages of lung development when there is minimal vascular development. In contrast, EMAP II is distributed around the large vessels during the end of vascular development, suggesting that EMAP II modulates the neovascularization process. We speculate that EMAP II is a director of neovascularization in the developing lung.

Animals↗

PubMed1999

Contribution of endogenous carbon monoxide to regulation of diameter in resistance vessels.

Endogenous carbon monoxide was proposed to subserve vasodepressor functions. If so, inhibition of heme oxygenase may be expected to promote vascular contraction. This hypothesis was examined in large and small arteries and in isolated first-order gracilis muscle arterioles of rat. The heme oxygenase inhibitors chromium mesoporphyrin (CrMP) and cobalt protoporphyrin (0.175-102 micromol/l) decreased the diameter of pressurized (80 mmHg) gracilis muscle arterioles, whereas magnesium protoporphyrin, a weak heme oxygenase inhibitor, did not. CrMP also elicited development of isometric tension in the muscular branch of the femoral artery but not in the aorta or femoral artery. Arteriolar constrictor responses to CrMP varied in relation to the intravascular pressure, were blunted in preparations exposed to exogenous carbon monoxide (100 micromol/l), and were unaffected by an endothelin receptor antagonist. Importantly, CrMP amplified the constrictor response to increases of pressure in gracilis arterioles. Accordingly, the constrictor effect of heme oxygenase inhibitors is attributable to magnification of myogenic tone due to withdrawal of a vasodilatory mechanism mediated by endogenous carbon monoxide. The study suggests that the vascular carbon monoxide system plays a role in the regulation of basal tone in resistance vessels.

Animals↗

PubMed1999

Expansion and immunological study of human tumor infiltrating gamma/delta T lymphocytes in vitro.

Goffa/delta T cells have stimulated a lot of interest because of their unique features in antigen recognition and cytotoxicities to many autologous and/or allogeneic tumor cells. We have developed a novel method to selectively expand larger amounts of human tumor-infiltrating gamma/delta T lymphocytes (gamma/delta TILs) ex vivo by immobilized pan- anti-TCRgamma/delta monoclonal antibody in the presence of exogenous IL-2. The expanded gamma/delta TILs mainly expressed CD45RO and HLA-DR molecules and did not express CD4. CD8+ gamma/delta TILs accounted for 19% of gamma/delta TILs. The expression of CD25 molecule on expanded gamma/delta T cells was inducible and downregulated following a time course. The Vdelta1 and Vdelta2 subsets amount to 37 and 58%, respectively. The expanded gamma/delta TILs show an IL-2-dependent proliferation, MHC class I-unrestricted and TCRgamma/delta-related cytotoxicities to two MHC class I+ and two MHC class I+ allogeneic tumor cell lines in vitro.

Adenocarcinoma↗

PubMed1999

Function of stem cell factor as a survival factor of spermatogonia and localization of messenger ribonucleic acid in the rat seminiferous epithelium.

To address the possibility that stem cell factor (SCF) is a paracrine regulator of germ cell development in the adult rat testis, stage-specific distribution of SCF messenger RNA (mRNA) was investigated with Northern blot and in situ hybridization analyses. The highest levels of SCF mRNA were found in stages II-VI of the rat seminiferous epithelial cycle, whereas the lowest levels were in stages VII-VIII. Intermediate levels of SCF mRNA were detected in stages IX-XIV-I of the cycle. The expression of the SCF gene was found to be developmentally regulated, and the expression pattern followed the process of Sertoli cell proliferation and differentiation during postnatal life. The effect of mouse recombinant SCF on spermatogonial DNA synthesis was studied using an in vitro tissue culture system for stage-defined seminiferous tubules. A significant increase in DNA synthesis in spermatogonia could be detected when tubule segments from stage XII were cultured in the presence of 100 ng/ml SCF for 48 h (P < 0.05) and 72 h (P < 0.01). This observation was further confirmed with autoradiographic analyses; almost a 100-fold increase in thymidine incorporation in the SCF-treated (100 ng/ml) tubule segments was observed compared with that in untreated samples. The results of the present study suggest that SCF is a Sertoli cell-produced paracrine regulator and acts as a survival factor for spermatogonia in the adult rat seminiferous epithelium in a stage-specific manner.

Animals↗

PubMed1999

Serratus anterior-rib composite flap: anatomic studies and clinical application to hand reconstruction.

Because of its relative ease of dissection, increased length of the vascular pedicle, and excellent diameter for anastomosis, the serratus anterior-rib composite flap has been used to reconstruct bony and soft-tissue defects in the face and lower extremities. However, no data are available on optimal rib level or harvest location. The authors report the results of the vascular anatomy of this flap in 6 fresh cadavers and 2 clinical patients using this flap to reconstruct a defect in the hand. Arteriograms were performed through the thoracodorsal artery, and microscopic dissections were done at the rib periosteum. The sixth through the ninth ribs showed consistent filling of their respective intercostal vessels. The rib segments near the anterior axillary line had the most abundant communicating vessels between the serratus and the periosteum. In two patients, the serratus-rib composite free flap provided excellent bone and muscle length for reconstructing the first metacarpal defect.

Adult↗

PubMed1999

Dose-dependent effects of DNA-damaging agents on p53-mediated cell cycle arrest.

We examined the dose-dependent effects of DNA-damaging agents on G1 arrest in isogenic human cell lines differing in their p53 status. As expected, 5 or 20 Gy of ionizing radiation induced a p53-dependent G1 arrest. In contrast, UV light or actinomycin D induced a modest G1 arrest that was p53-dependent only at lower doses. At higher doses, cells were arrested in G1 in a p53-independent manner coinciding with inhibition of RNA synthesis and abolished cyclin E expression. Interestingly, expression of cyclin E was enhanced after exposure to moderate doses of UV light and actinomycin D, and this enhancement was suppressed by wild-type p53. We propose that agents inducing transcription-blocking DNA lesions will at higher doses inhibit the progression of cells into S phase by a p53-independent mechanism involving the attenuation of E2F-mediated transcription of genes, such as cyclin E.

Blotting, Western↗

PubMed1999

Effects of electro-acupuncture on somatostatin and pancreatic polypeptide in ischemic cerebrovascular diseases.

The levels of somatostatin (SS) in CSF and blood and pancreatic polypeptide (PP) in plasma were measured by radioimmunoassay in 64 patients with acute ischemic cerebrovascular diseases (ICVD), randomly divided into two groups: group 1 (n = 31, both electro-acupuncture and routine treatments given) and group 2 (n = 33, routine treatment) and 26 non-ICVD patients were used as controls. The points of electro-acupuncture were Quchi (LI 12), Waiguan (SJ 5) and Huantiao (GB 30) and Zusanli (St 36). After a course of treatment, the SS levels in plasma and CSF were significantly increased in the patients of group 1 with good result and their plasma PP level had no significant change. In the patients with poor result, however, the PP level was significantly decreased. The results suggested that electro-acupuncture might play an active role in alleviating the SS metabolic disturbance in CNS of ICVD patients.

Adult↗

PubMed1999

Patterns of flap loss related to arterial and venous insufficiency in the rat pedicled TRAM flap.

Vascular supply to the contralateral portion of the conventional transverse rectus abdominis musculocutaneous (TRAM) flap (zone IV) may become compromised, resulting in partial flap loss and requiring segmental excision. The etiology of this necrosis is not clear. This study determines skin necrosis patterns on a superiorly pedicled caudal TRAM flap during conditions of venous and arterial insufficiency, and determines whether cutaneous venous outflow can sustain a flap with venous insufficiency. Twenty-eight adult male Sprague-Dawley rats underwent superior pedicled TRAM flap elevation, and the zones were marked on the skin paddle. The animals were divided into four groups: control (group A, N = 6), arterial ligation (group B, N = 6), venous ligation (group C, N = 8), and venous ligation with cutaneous venous outflow (group D, N = 8). After 10 days, the skin paddle was photographed and the areas of necrotic skin were measured. Results showed that group B (selective arterial ligation) had 51.7 +/- 2.8% and 40.0 +/- 2.0% skin necrosis in zones I and II respectively. Zone I necrosis was significantly greater in group B compared with the control (p < 0.05). Group C (selective venous ligation) resulted in 73.8 +/- 16.4% and 93.8 +/- 33.4% skin necrosis in zones III and IV respectively. This necrosis was significantly greater compared with the control (p < 0.001). Group D rats' lateral skin necrosis compared significantly less with group C (p < 0.001). These results demonstrate that the patterns of flap necrosis in rat TRAM flaps with poor arterial inflow differ from those with venous stasis. Necrosis of the contralateral portion (zone IV) of human TRAM flaps may be related to problems with venous stasis; thus, a cutaneous venous outflow may prevent this problem.

Animals↗

PubMed1999

Effects of VEGF administration following ischemia on survival of the gracilis muscle flap in the rat.

The incidence of free flap transplantation failure is only 3% to 5%, yet still occurs in cases in which the flap suffers prolonged ischemia. The purpose of the current study was to determine the effects of vascular endothelial growth factor (VEGF)--a potent angiogenic agent with a suspected role in the protection of endothelium--on flap survival in a model of ischemia-reperfusion injury. The model chosen was the rat gracilis muscle flap. A total of 36 adult male Sprague-Dawley rats were divided into three groups (N = 12). One experimental group received VEGF treatment and the other received heparin. A third group was treated with saline and served as the control. The gracilis muscle flap was dissected and isolated based on a vascular pedicle originating at the femoral vessels. Following 3.75 hours of ischemia, induced by clamping the femoral vessels, either VEGF, heparin, or saline was infused directly into the pedicle of the flap via a cannula. The flaps were evaluated both grossly and histologically after 72 hours of reperfusion. Eleven of the 12 flaps from the VEGF group survived, whereas the survival rate was 6 of 12 and 5 of 12 flaps for the heparin- and saline-treated groups respectively. Flap survival was significantly greater in the VEGF-treated group compared with the heparin- and saline-treated groups (p < 0.025, p < 0.01 respectively). Furthermore, there was no significant difference between the heparin and saline groups. These results indicate that VEGF plays a role in reducing the damage that occurs in ischemia-reperfusion injury, and that the use of VEGF holds promise as a potential therapy for increasing flap survival.

Animals↗

PubMed1999

Effects of transient forebrain ischemia and radix Salviae miltiorrhizae (RSM) on extracellular levels of monoamine neurotransmitters and metabolites in the gerbil striatum--an in vivo microdialysis study.

The aim of this study was to investigate the effect of 30 min forebrain ischemia, followed by 120 min reperfusion on extracellular fluid (ECF) levels of dopamine (DA), norepinephrine (NE), serotonin (5-HT) and their metabolites, homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in the striatum of gerbils, so as to obtain further information on the mechanism of Radix Salviae Miltiorrhizae (RSM)-induced neuroprotection. Microdialysis was used to sample the extracellular space. Dialysate was measured by high performance liquid chromatography with electrochemical detector (HPLC-ED). ECF DA, NE levels increased from basal levels by 282, 227 and 221 folds, by 9.14, 8.51 and 8.25 folds, respectively for the three ischemic duration (0-10; 11-20; 21-30 min). ECF DA, NE, 5-HT levels in the RSM-treated group were significantly decreased as compared with those in the control group during ischemia (P < 0.01). The results suggested that monoamine neurotransmitters were involved in ischemic neuron damage directly or indirectly; and that RSM plays a protective role during cerebral ischemia by attenuating the dysfunctions of monoamine neurotransmitters.

Animals↗

PubMed1999

Clinical hereditary characteristics in nasopharyngeal carcinoma through Ye-Liang's family cluster.

OBJECTIVE: To investigate the incidence of nasopharyngeal carcinoma (NPC) and the clinical characteristics in this family through a long-term follow-up, and to seek the hereditary factor of NPC. This research was also designed to provide some clinical data for etiological study. METHODS: A genealogical tree of Ye-Liang's family was drawn and reported in 1972 after a complete survey. Further follow-up from that time to 1997 was performed. Human leucocyte antigens (HLA) were investigated, and physical follow-up was done in domestic members of this family. For oversea members of this family, correspondence follow-up was performed. RESULTS: In the last 25 years, the incidence of malignancies in Ye-Liang's family increased from 10 cases to 18 cases, and incidence of NPC increased from 9 cases to 15 cases. In this family, not only multiple malignancies have been found in the second generation, but also NPC has been found in the third generation. HLA-[A2-B46] haplotype was correlated with occurrence of NPC. CONCLUSIONS: Dominant racial predilection and family cluster in NPC implied that NPC is a heredity-related cancer which might involve multifactorial disorders in carcinogenesis. Further research on etiology of NPC should be focused on hereditary factor. Detection of inherited factors should be performed for forecast of carcinogenesis and reduction of NPC occurrence.

Female↗