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Biomedical subjects

J Fan

Publications and source records attributed to J Fan.

At least 109 records · Page 6Linked to original sources
PubMed2000

Liposomal antioxidants provide prolonged protection against acute respiratory distress syndrome.

BACKGROUND: We have previously shown that N-acetylcysteine (NAC), an antioxidant, in the resuscitation fluid after shock prevents lung injury in response to lipopolysaccharide (LPS) by inhibiting chemokine generation by alveolar macrophages in the lung. However, the protection was short-lived. We hypothesized that liposomal (Lip) NAC delivered intratracheally might be delivered directly to the target cells and exert prolonged effect. METHODS: Sprague-Dawley rats were bled to a blood pressure of 40 mm Hg for 1 hour and resuscitated with shed blood and equal volume of Ringer's lactate. In some studies 500 mg/kg NAC was included in the resuscitation fluid. Thirty minutes later, 150 microl LipNAC (9.4 mg/kg NAC) was given intratracheally. One hour and 18 hours after resuscitation, LPS (30 microg/kg) or saline was given intratracheally. Lung injury was assessed by permeability to (125)I-albumin, bronchoalveolar lavage neutrophils and lung myeloperoxidase. The cytokine-induced neutrophil chemoattractant (CINC) expression in the lung was assessed by Northern blot. RESULTS: At the early time point, both NAC and LipNAC protected the lung with the effects in significantly reducing the increases in transpulmonary albumin flux, neutrophil influx and myeloperoxidase in the lungs of shock/LPS rats. However, by the late time point, only LipNAC retained its salutary effect. This correlated well with persistent ability to prevent CINC increase. In addition, Lipalpha-tocopherol (alpha-T) and LipNAC/alpha-T were tested and determined to be effective to protect the lung. CONCLUSIONS: Liposomal encapsulation of antioxidants at low dose provides long lasting protection against acute respiratory distress syndrome after shock. This may represent a novel treatment approach.

Acetylcysteine↗
PubMed2000

Phase I clinical trial of oral furtulon and combined hepatic arterial chemoembolization and radiotherapy in unresectable primary liver cancers, including clinicopathologic study.

Surgical resection has been accepted as the only curative therapy for primary liver cancer (PLC). Unfortunately, most patients are surgically unresectable when they seek treatment. An alternative therapeutic approach for some of these patients is transcatheter arterial chemoembolization. However, this is not curative by itself, and additional therapy is required to eradicate residual disease. This study investigates the approach of preoperative hepatic arterial chemoembolization followed by the combination of oral Furtulon (5'-deoxy-5-fluorouridine) as a radiosensitizer and external beam radiotherapy (RT). From July 1997 to December 1998, 25 patients with unresectable PLC were treated with hepatic arterial chemoembolization followed by limited-field radiotherapy plus oral Furtulon as a radiosensitizer. Hepatic arterial chemoembolization was performed with 5-fluorouracil 1 g, cisplatin 80 mg (DDP), mitomycin C (MMC) 10 mg, and arterial embolization with iodized oil-10 ml mixed with 10 mg MMC. Hepatic arterial chemoembolization was performed at regular intervals of 6 weeks, and the patients then received limited-field RT. Mean tumor dose was 4,600 cGy (range, 4,100-5,200 cGy) in daily 1.8-Gy fractions, 5 times a week. The toxicity and responses between RT and surgery were assessed. After surgical evaluation, resection was performed. The histopathologic study was also performed in the specimens of both normal and radiation-injured liver tissues from the patients who underwent resection. Seventeen of 25 patients (68%) showed an objective response. One patient with cholangiocarcinoma involving the portal lymph nodes attained a complete response. Eight patients (32%) underwent sequential resection. The most common toxicity was an increase in liver enzymes, which were less than twofold of the upper limit of normal. Follow-up computed tomography studies after treatment showed a low-attenuation area adjacent to the hepatic tumor in the target volume. On pathologic evaluation, the low-attenuation area revealed hyperemia, distended hepatic sinusoids packed with erythrocytes, and hepatic cell loss when examined with microscopy; "new-born" hepatocytes, hepatic cords in the process of forming, and endothelial cells have appeared on electronic microscopic examination. The combination of hepatic arterial chemoembolization and external radiotherapy is efficacious and a safe modality for unresectable primary liver cancers. Furtulon offers the potential for use as a clinical radiosensitizer. Radiation can significantly damage the liver tissue between 41 Gy and 52 Gy, but the new hepatocytes were forming within the radiation-injured liver after RT.

Adult↗
PubMed2000

A new technique of scarless expanded forehead flap for reconstructive surgery.

The forehead flap is an ideal flap for reconstructive surgery, especially for that involving reconstruction of the face and neck. However, it is usually limited to use in nasal reconstruction, even when performed in conjunction with tissue expansion, because of the severe visible morbidity of the donor site. In this article, the author discusses his development of a new technique of forehead flap, performed in conjunction with tissue expansion, for reconstructive surgery without visible scarring at the donor site. The technique involved positioning a tissue expander in the forehead pocket under the occipitofrontal muscle and serially inflating the expander over a period of approximately 4 to 6 weeks. Thereafter, an expanded forehead flap was created from the frontal hairline area on the basis of the location of the superficial temporal vessels and transferred into 16 recipient sites in 13 patients as an island flap (n = 8), a free flap (n = 1), or a local random flap (n = 7). The donor site was closed directly into the frontal hairline, without any visible scar. With the author's experience in the use of the island flap for nasal, facial, and neck reconstruction and of the free flap for reconstruction in the extremities, the flap could be as large as 8 x 18 cm without inducing flap necrosis or problems with donor-site closure. All patients (n = 13) had acceptable donor-site aesthetic results, without visible scarring. The results indicate that the flap could be a safe, ample, and color-matched flap for reconstruction of the face and neck and could also diminish donor-site morbidity to a minimum, without an unsightly visible scar. Furthermore, the flap could be formed into a customized free flap, with the above-mentioned advantages, to be transferred to any part of the body.

Adolescent↗
PubMed2000

In vivo and in vitro modulation of intercellular adhesion molecule (ICAM)-1 expression by hypertonicity.

Hepatic ischemia-reperfusion (I/R) is an important cause of organ dysfunction in the critically ill. With reperfusion, Kupffer cells release pro-inflammatory cytokines that promote endothelial cell (EC) expression of adhesion molecules such as intercellular adhesion molecule (ICAM)-1, facilitating neutrophil (PMN) infiltration. Studies suggest hypertonic saline (HTS) might exert beneficial effects on development of organ injury following shock on the basis of reduced PMN-EC interactions. We hypothesized that HTS alters expression of EC ICAM-1 and thus minimizes PMN-mediated injury. To test our hypothesis, we used an in vivo model of hepatic I/R and an in vitro model of activated EC. Rats underwent 30 min of hepatic ischemia after pretreatment with HTS (7.5% NaCl, 4cc/kg ia) or normal saline (NS). At 4 h reperfusion, plasma was taken for aspartate aminotransferase (AST) and liver tissue was harvested for assessment of hepatic ICAM-1 mRNA by Northern blot analysis. Human umbilical vein endothelial cells (HUVECs) were activated by lipopolysaccharide (LPS) and exposed to hypertonic medium (350-500 mOsM). HUVEC ICAM-1 protein was measured by cell ELISA and ICAM-1 mRNA by Northern blot analysis. HTS prevented hepatic I/R injury as measured by AST. AST of shams was 282.6+/-38.1 IU/L. I/R following NS pretreatment caused significant injury (AST 973.8+/-110.9 IU/L) compared to sham (SM) (P < 0.001). Pretreatment with HTS exerted significant protection following I/R with an AST of 450.9+/-56.3 IU/L (P < 0.05). There was no significant difference in AST levels between SM and HTS groups. Reduced hepatic injury after HTS and I/R was accompanied by inhibition of I/R-induced hepatic ICAM-1 mRNA expression compared to NS treated animals (P < 0.01). Similarly, hypertonicity inhibited HUVEC LPS-induced ICAM-1 protein (LPS: 1.86+/-0.19 absorbance units; 400 mOsM +/- LPS: 1.45+/-0.14 absorbance units; 450 mOsM + LPS: 1.02+/-0.19 absorbance units, P < 0.001) and mRNA expression. Thus, hypertonicity modulates endothelial ICAM-1 expression as one possible protective mechanism against I/R injury.

Animals↗
PubMed2000

X-ray and extreme ultraviolet emission induced by variable pulse-width irradiation of Ar and Kr clusters and droplets

Measurements are presented of x-ray (>1.5 keV) and extreme ultraviolet (EUV, lambda=2-44 nm) emission from argon and krypton supersonic gas jets at room (T=300 K) and cryogenic (T=173 K) temperatures irradiated with constant energy (50 mJ), variable width laser pulses ranging from 100 fs to 10 ns. Two regimes of jet operation are explored: cluster formation (radius<100 nm) and droplet formation (radius>1 &mgr;m). The results for both clusters and droplets can be understood in terms of two time scales: a short time scale for optimal resonant absorption at the critical density layer in the expanding plasma, and a longer time scale for the plasma to drop below critical density.

Journal Article↗
PubMed2000

Tubular plasma generation with a high-power hollow bessel beam

A high power, hollow Bessel beam (J5) is generated using an axicon and a phase plate in combination. The optical breakdown of a gas target and generation of a tubular plasma fiber with such a beam is realized. Hydrodynamic simulations of the hollow beam-plasma breakdown and heating are in reasonable agreement with interferometric measurements of the plasma time evolution.

Journal Article↗
PubMed2000

cis,cis,cis-tetramethyl 1,2,4,5-cyclohexanetetracarboxylate

The title compound, C(14)H(20)O(8), was synthesized from the hydrogenation of tetramethyl 1,4-cyclohexadiene-1,2,4, 5-tetracarboxylate with a catalytic amount of palladium/carbon. All four carbonyl moieties of the methyl ester groups are on the same face of the chair-conformed ring. The substantial ring distortion associated with the 1,3-diaxial methoxycarbonyl substituents is reflected in the large difference between bond angles as well as torsion angles, respectively, that in undistorted cyclohexanes would be approximately the same.

Journal Article↗
PubMed2000

Role of endothelin-1 in atherosclerosis.

Increased evidence has shown that endothelin-1 (ET-1) derived from the arterial cells is involved in the development of atherosclerosis. ET-1 and ET receptors are upregulated in both human and experimental animal atherosclerotic lesions. Plasma ET-1 levels are significantly elevated in hypercholestolemic subjects and cholesterol-fed animals. We hypothesized that plasma lipoproteins such as LDL and HDL retained in the arterial wall can affect ET-1 production and secretion, thereby sustaining vascular functions. Using a two-chamber culture system, we have demonstrated that endothelial cells (ECs) show a polar secretion of ET-1; the majority of ET-1 are secreted toward the basal side of the vessels. Furthermore, we found that LDL enhances whereas HDL inhibits the ET-1 secretion from ECs in a polarized pattern. In order to demonstrate ET receptor distribution in the lesion, we recently studied both human and apoE-KO mice. Our study showed that there is an increased expression of ETB receptors in foamy macrophages in the lesions. More importantly, medial smooth muscle cells (SMCs) beneath the foam cell lesions exhibited a higher intensity of ETB receptor immunoreactivity than those located in foam cell-free areas. In such an area, ET-1 immunoreactivity is also increased. These results suggest that accumulation of foamy macrophages may modulate the shift of ET receptor subtypes from ETA to ETB in SMCs and an enhanced ET system mediated by ETB receptors may play a pivotal role in the progression of atherosclerosis. This notion has been further supported by a recent finding that administration of ET receptor antagonists resulted in a significant reduction of atherosclerosis in apoE-KO mice.

Animals↗
PubMed2000

Cytokine gene expression occurs more rapidly in stimulated peripheral blood mononuclear cells from human immunodeficiency virus-infected persons.

Evaluation of cytokine gene expression following in vitro stimulation is one means of examining the dysregulation of the immune system in human immunodeficiency virus (HIV) infection. We have assessed differences in the immune status of non-HIV-infected (HIV-) and HIV-infected (HIV+) individuals by evaluating the kinetics of the expression of cytokine genes. We compared detailed time courses of cytokine mRNA expression in HIV- and HIV+ peripheral blood mononuclear cells (PBMC) and found that there is a significant shift (P<0.01) for all cytokines examined (interleukin 2 [IL-2], IL-6, IL-10, gamma interferon, and tumor necrosis factor alpha [TNF-alpha]) to an earlier time of mean peak mRNA expression by HIV+ PBMC (between 4 and 8 h) compared to HIV- PBMC (8 h) in response to either phytohemagglutinin (PHA) or anti-CD3 stimulation. Additional studies showed that although PHA-stimulated HIV+ PBMC showed decreased median IL-2, IL-4, and TNF-alpha mRNA levels, they typically demonstrated more rapid kinetics (increased mean 4-h/24-h cytokine mRNA ratios), with significant differences for IL-4 (P<0.05) and TNF-alpha (P<0.005), compared to HIV- PBMC. The use of fresh or frozen cells gave comparable cytokine mRNA data; however, the secretion of some cytokine proteins (IL-2 receptor, IL-10, and TNF-alpha) appeared to be reduced in HIV+ PBMC that had been frozen and thawed. Our studies demonstrate that the kinetics of cytokine gene expression can reveal additional dysregulation of the immune system in HIV infection, suggesting that PBMC of HIV-infected persons exist in an activated state in vivo that permits them to express cytokine genes more rapidly than a normal PBMC.

Cells, Cultured↗
PubMed2000

Direct PCR of Cryptococcus neoformans MATalpha and MATa pheromones to determine mating type, ploidy, and variety: a tool for epidemiological and molecular pathogenesis studies.

Cryptococcus neoformans MATalpha and MATa pheromones were amplified by direct PCR. Nucleotide sequence analyses revealed unique restriction enzyme sites. Sixty strains were used to devise a restriction fragment length polymorphism typing scheme that yielded three variety-specific patterns. Additionally, pheromone-specific PCR allowed easier identification of diploid C. neoformans strains than flow cytometry.

Cryptococcosis↗
PubMed2000

Priming for enhanced alveolar fibrin deposition after hemorrhagic shock: role of tumor necrosis factor.

Hemorrhagic shock due to major trauma predisposes to the development of acute respiratory distress syndrome. Because lung fibrin deposition is one of the hallmarks of this syndrome, we hypothesized that resuscitated shock might predispose to the development of a net procoagulant state in the lung. A rodent model of shock/resuscitation followed by low-dose intratracheal lipopolysaccharide (LPS), a clinically relevant "two-hit" model, was used to test this hypothesis. Resuscitated shock primed the lungs for an increased tissue factor and plasminogen activator (PA) inhibitor-1 gene expression in response to LPS, while the fibrinolytic PA was reduced. These alterations were recapitulated in isolated alveolar macrophages, suggesting their role in the process. LPS-induced tumor necrosis factor (TNF) was also augmented in animals after antecedent shock/resuscitation, and studies using anti-TNF antibodies revealed that TNF expression was critical to the induction of the procoagulant molecules and the reduction in PA. By contrast, TNF did not appear to play an important role in neutrophil sequestration in this model, inasmuch as anti-TNF had no effect on lung neutrophil accumulation or chemokine expression. However, treatment prevented albumin leak by preventing alveolar neutrophil activation. The inclusion of the antioxidant N-acetyl-cysteine in the resuscitation fluid resulted in prevention of both the development of the net procoagulant state and lung neutrophil sequestration, suggesting a role for upstream oxidant effects in the priming process. These studies provide a cellular and molecular basis for lung fibrin deposition after resuscitated shock and demonstrate a divergence of pathways responsible for fibrin generation and neutrophil accumulation.

Acetylcysteine↗
PubMed2000

Cholesterol-fed and transgenic rabbit models for the study of atherosclerosis.

The rabbit has been extensively utilized as an ideal model of atherosclerosis because of its size, easy manipulation, and extraordinary response to dietary cholesterol. The availability of spontaneously hypercholesterolemic model, Watanabe heritable hyperlipidemic rabbits (WHHL) and St. Thomas rabbits, has also provided insights into understanding human familiar hypercholesterolemia and atherosclerosis. With the advent of genetically engineered rabbits, transgenic rabbits have become a novel means to explore a number of proteins that are associated with cardiovascular diseases including atherosclerosis. To date, transgenes for human apo(a), apoA-I, apoB, apoE2, apoE3, hepatic lipase, lecithin: cholesterol acyltransferase (LCAT), lipoprotein lipase, 15-lipoxygenase, as well as for rabbit apolipoprotein B mRNA-editing enzyme catalytic polypeptide 1 (APOBEC-1), have been expressed in rabbits. In addition, human apoA-I, LCAT and apo(a) have been introduced into WHHL rabbits which have deficient LDL receptor function. All of these transgenes have been found to have significant effects on plasma lipoprotein metabolism or/and atherosclerosis. These studies have revealed new insights into the mechanisms responsible for the development of atherosclerosis. In this article, we provide a brief review on the rabbit model for the study of atherosclerosis with emphasis on transgenic rabbit models developed during the past few years.

APOBEC-1 Deaminase↗
PubMed2000

Transgenic rabbits expressing human apolipoprotein (a).

Elevated plasma levels of lipoprotein (a) [Lp(a)] constitutes an independent risk factor for coronary heart disease, stroke, and restenosis. Over the past years, our understanding of the genetics, metabolism and pathophysiology of Lp(a) have increased considerably. However, the precise mechanism(s) by which this atherogenic lipoprotein mediates the development of atherosclerosis remains unclear. This is partly due to the lack of appropriate animal models since apolipoprotein (a) [apo(a)], a distinct component of Lp(a) is found only in primates and humans. Development of transgenic mice expressing human apo(a) has provided an alternative means to investigate many aspects of Lp(a). However, human apo(a) in transgenic mice can not bind to murine apoB to form Lp(a) particles. In this aspect, we generated transgenic rabbits expressing human apo(a). In the plasma of transgenic rabbits, unlike the plasma of transgenic mice, about 80% of the apo(a) was associated with rabbit apo B and was contained in the fractions with density 1.02-1.10 g/ml, indicating the formation of Lp(a). Our study suggests that transgenic rabbits expressing human apo(a) exhibit efficient assembly of Lp(a) and can be used as an animal model for the study of human Lp(a).

Animals↗
PubMed2000

Defects of the LDL receptor in WHHL transgenic rabbits lead to a marked accumulation of plasma lipoprotein[a].

In this study, we created LDL receptor (LDLr) defective (WHHL) transgenic rabbits expressing human apo[a] to examine whether LDLr mediates the Lp[a] clearance from the plasma. By crossbreeding WHHL rabbits with human apo[a] transgenic rabbits, we obtained two groups of human apo[a] transgenic rabbits with defective LDLr functions: apo[a](1/0) WHHL heterozygous (LDLr(+/-) and apo[a](+/0) WHHL homozygous (LDLr(-/-) rabbits. The lipid and lipoprotein levels of human apo[a] WHHL rabbits were compared to those of human apo[a] transgenic rabbits with normal LDLr functions (LDLr(+/+). The apo[a] production rate was evaluated by analyzing apo[a] mRNA expression in the liver, the major site for apo[a] synthesis in transgenic rabbits. We found that pre-beta lipoproteins were markedly increased accompanied by a 2-fold increase in the plasma Lp[a] in apo[a](+/0)/LDLr(+/-) rabbits and a 4.2-fold increase in apo[a](+/0)/LDLr(-/-) rabbits compared with that in apo[a](+/0) rabbits with normal LDLr function. In apo[a](+/0)/LDLr(-/-) rabbits, there was a marked increase in plasma total cholesterol and triglycerides, as was found in their counterpart non-transgenic WHHL rabbits. Northern blot analysis revealed that hepatic apo[a] expression in WHHL transgenic rabbits was similar to that in LDLr(+/+) transgenic rabbits, suggesting the accumulation of plasma Lp[a] in WHHL transgenic rabbits was not due to increased apo[a] synthesis. In conclusion, absence of a functional LDLr leads to a marked accumulation of plasma Lp[a] in human apo[a] transgenic WHHL rabbits and LDLr may participate in the catabolism of Lp[a] in rabbits.

Animals↗
PubMed2000

[Effects of pravastatin on hepatic plasminogen activator inhibitor 1 mRNA expression in rabbits with fatty liver].

OBJECTIVE: To explore the effects of Pravastatin on the changes of plasminogen activator inhibitor 1 (PAI-1) gene expression of hepatic tissue in rabbit with fatty liver. METHODS: We observed the influences of Pravastatin on the rabbit model of hyperlipidemia and fatty liver induced by high fat diet for 12 weeks, and the plasma PAI-1 activity and the hepatic PAI-1 mRNA expression in therapeutic group (n=10); and meanwhile, designed the model group (n=10) and normal group (n=7) as control. RESULTS: Severe hepatocellular steatosis was found in model group compared with normal group. Plasma lipids and PAI-1 activity increased in model group in 6 and 12 weeks, and was significantly higher than normal group in 12 weeks. PAI-1 mRNA relative values in hepatic tissue in model group were higher than those in normal group. Compared with model group, hepatic pathological manifestation with the respect of steatosis had no obvious changes in therapeutic group, but the lipid content and PAI-1 activity in the plasma and the expression of PAI-1 mRNA in the liver were significantly reduced. The activity of PAI was (14.0A2. 5)X10(-3)U/L in model group, and (8.6A2.0)X10(-3)U/L in therapeutic group in 12 weeks. CONCLUSION: Pravastatin could inhibit over-expression of PAI-1 mRNA in the rabbit liver with hyperlipidemia and fatty liver, and reduce its plasma PAI-1 activity.

Animals↗
PubMed2000

Differential diagnosis between hepatic focal nodular hyperplasia and hepatocellular carcinoma with negative alhpa-fetoprotein.

OBJECTIVE: To study the differential diagnosis between hepatic focal nodular hyperplasia (FNH) and hepatocellular carcinoma (HCC) with negative alpha-feto protein. METHODS: To analyse retrospectively the clinical and imaging materials of 18 patients with FNH and 254 patients with AFP negative HCC proven by operation and pathology during March 1996 to March 1999 in our institute. RESULTS: Patients with FNH were largely younger (66.7% under 40 years), discovered accidentally (66.7%), and without hepatitis background (83.3%). Majority of them had a normal liver function (72.0%). A big central artery was found in the lesion with high velocity and low resistant index in 71.4% of patients by color Doppler ultrasound. CT scan showed transient immediate enhancement in 85.7% of patients after bolus injection, being homogeneous (53.3%) and isodensity (73.3%) in the portal vein phase. MR imaging demonstrated early vigorous enhancement (83.3%) and homogenous (66.7%) lesion. In contrast, patients with AFP negative HCC were generally older (85.8% over 40 years), with symptoms (74.0%). A color flow with high velocity and high resistant index was found by color Doppler ultrasound. CT scan showed early heterogenous enhancement (96.6%) after bolus injection and being hypodensity in portal vein phase. MR imaging indicated early heterogeneous enhancement (91.7%). CONCLUSION: FNH shows some typical clinical and imaging features. Therefore, it is feasible to be differentiated from HCC with negative AFP in some of the patients.

Adolescent↗
PubMed2000

DNA damage and activation of c-ras in human embryo lung cells exposed to chrysotile and cigarette smoking solution.

Epidemiological studies and animal experiments showed that asbestos and cigarette smoking can act synergistically in the development of lung cancer. The mechanism of this synergism is largely unknown. It is well documented that DNA damage and activation of oncogenes play important roles in the development of cancer. The aim of our study was to find out if DNA damage could be increased and c-ras oncogene could be activated when human embryo lung cells were treated with chrysotile (CH) and cigarette smoking solution (CSS) separately or simultaneously. Human embryo lung (HEL) cells were treated with different doses of CH and CSS separately or simultaneously, then DNA strand breaks were detected with single-cell gel electrophoresis assay and the expression of p21 was detected by flow cytometry. Factorial analysis was used to evaluate the combined effect of chrysotile and cigarette smoking solution. The results showed that DNA strand breaks could be increased significantly when HEL cells were exposed to CH and CSS separately for 1 hour and increased in a dose-dependent relationship when cells were exposed to CH and CSS simultaneously for 1 hour. The expression of p21 increased significantly when cells were exposed to CH for 24 hours, but there was no significant increase when cells were exposed to CSS for 24 hours. However, there was an additive effect on the expression of p21 when cells were exposed to CH and CSS simultaneously for 24 hours. When cells were exposed to CH and CSS simultaneously three times (24 hours each time), then passaged for 1 month, the expression of p21 increased synergistically. In conclusion, DNA damage and activation of c-ras may be involved in the process of combined carcinogenesis of CH and CSS.

Asbestos, Serpentine↗