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Biomedical subjects

B Zhao

Publications and source records attributed to B Zhao.

At least 19 recordsLinked to original sources
PubMed1998

Involvement of cytokines in normal CNS development and neurological diseases: recent progress and perspectives.

Cytokines have been recognized to play an important role both in normal development of the brain, when they act as neurotrophic factors, as well as following injury. While both the cytokines and their receptors are synthesized and expressed in the brain normally (albeit at low levels), it has become clear that elevated levels are associated with many neurological disorders. In this review, we have chosen to present the data for only a few of the cytokines, including interleukin-1beta, interleukin-3, interleukin-6, interferon-gamma, transforming growth factor-beta, and tumor necrosis factor-alpha. Data are presented that suggest roles they may play in human disorders, including stroke, multiple sclerosis, Alzheimer's disease, and several psychiatric disorders. The results in human disease are compared with results obtained in a variety of transgenic animal models. The mouse models have very different disorders depending on whether a cytokine is overexpressed either peripherally or in either astrocytes or neurons. The potential significance of this to the understanding of human disease is discussed.

Animals↗
PubMed1998

The myogenic regulatory gene Mef2 is a direct target for transcriptional activation by Twist during Drosophila myogenesis.

MEF2 is a MADS-box transcription factor required for muscle development in Drosophila. Here, we show that the bHLH transcription factor Twist directly regulates Mef2 expression in adult somatic muscle precursor cells via a 175-bp enhancer located 2245 bp upstream of the transcriptional start site. Within this element, a single evolutionarily conserved E box is essential for enhancer activity. Twist protein can bind to this E box to activate Mef2 transcription, and ectopic expression of twist results in ectopic activation of the wild-type 175-bp enhancer. By use of a temperature-sensitive mutant of twist, we show that activation of Mef2 transcription via this enhancer by Twist is required for normal adult muscle development, and reduction in Twist function results in phenotypes similar to those observed previously in Mef2 mutant adults. The 175-bp enhancer is also active in the embryonic mesoderm, indicating that this enhancer functions at multiple times during development, and its function is dependent on the same conserved E box. In embryos, a reduction in Twist function also strongly reduced Mef2 expression. These findings define a novel transcriptional pathway required for skeletal muscle development and identify Twist as an essential and direct regulator of Mef2 expression in the somatic mesoderm.

Animals↗
PubMed1998

Oxidized LDL damages endothelial cell monolayer and promotes thrombocyte adhesion.

The influence of oxidized low density lipoprotein (LDL) on a human endothelial cell monolayer was examined. The resulting contraction of the oxidized LDL-damaged endothelial cells lets intercellular spaces become enlarged and therefore visible via light microscopy. Electron microscopy reveals that the structural damage facilitates thrombocyte adhesion and formation of microthrombi. Oxidized LDL appears to play a pivotal role in initiating and deteriorating thromboembolic complications.

Blood Platelets↗
PubMed1997

Design of potent and selective human cathepsin K inhibitors that span the active site.

Potent and selective active-site-spanning inhibitors have been designed for cathepsin K, a cysteine protease unique to osteoclasts. They act by mechanisms that involve tight binding intermediates, potentially on a hydrolytic pathway. X-ray crystallographic, MS, NMR spectroscopic, and kinetic studies of the mechanisms of inhibition indicate that different intermediates or transition states are being represented that are dependent on the conditions of measurement and the specific groups flanking the carbonyl in the inhibitor. The species observed crystallographically are most consistent with tetrahedral intermediates that may be close approximations of those that occur during substrate hydrolysis. Initial kinetic studies suggest the possibility of irreversible and reversible active-site modification. Representative inhibitors have demonstrated antiresorptive activity both in vitro and in vivo and therefore are promising leads for therapeutic agents for the treatment of osteoporosis. Expansion of these inhibitor concepts can be envisioned for the many other cysteine proteases implicated for therapeutic intervention.

Binding Sites↗
PubMed1997

Processing of Alzheimer's amyloid precursor protein during H2O2-induced apoptosis in human neuronal cells.

The processing of Alzheimer's amyloid precursor protein was studied by Western blotting during H2O2 induced apoptosis in cultures of human neuroblastoma cells. A new 5.5 kDa fragment putatively containing intact A beta was detected and found to be highly associated with apoptosis. The results suggest a possible vicious cycle involving H2O2, A beta and apoptosis which may contribute to the neuronal death mechanism in Alzheimer's Disease.

Alzheimer Disease↗
PubMed1997

Expression of mutant amyloid precursor proteins induces apoptosis in PC12 cells.

The cause of neuronal loss in Alzheimer disease is unknown. We investigated the effects on survival of PC12 cells expressing A692G, E693Q, and V717F mutant amyloid precursor proteins (APP). Differentiated cells expressing mutant APPs exhibited somal shrinkage, followed by cell detachment from the plates. Increased levels of oligonucleosome-sized DNA ladders and TUNEL-positive nuclei were observed, and electron microscopy revealed extensive plasma membrane blebbing, margination of condensed chromatin, and well-preserved organelles in these transfectants. The levels of TUNEL-positive cells, analyzed by a flow-cytometric method, were increased by four- to sevenfold in mutant APP transfectants, but less than twofold in wild-type APP transfectants relative to untransfected cells. Our results provide evidence that expression of mutant APPs in differentiated PC12 cells induces cell death via an apoptotic pathway.

Amyloid beta-Protein Precursor↗
PubMed1997

Effect of dexamethasone on rat plasma platelet activating factor acetylhydrolase during the perinatal period.

It has been previously reported that the administration of dexamethasone (DEX) to adult rats increases the activity of plasma platelet-activating factor acetylhydrolase (PAF-AH) and prevents the development of intestinal necrosis caused by platelet activating factor (PAF) injection. In this report, we examined the effect of DEX administration on plasma PAF-AH activity during the perinatal period. Timed-pregnant rats received DEX (0.2-1.0 mg/kg/d) or normal saline (controls) on days 16-18 (early group) or days 18-20 (late group) of gestation. Maternal plasma PAF-AH activity was lower in late gestation than in postpartum period (P < 0.001). Fetal and neonatal plasma PAF-AH activity was higher than maternal values (P < 0.05). No changes of PAF-AH activity were seen in maternal, fetal or neonatal plasma after prenatal DEX administration at the aforementioned doses. A higher dose of DEX (1.3 mg/kg/d x 4d) or cortisone (200 mg/kg/d) produced an elevation of maternal plasma PAF-AH activity (DEX 79.2+/-3.0, cortisone 70.5+/-1.9 vs. controls 49.4+/-2.3 nmol/min/ml, P < 0.01), but resulted in a high fetal mortality. Treatment of newborn rats with DEX (0.5 mg/kg/d) on days 1-3 after birth, increased plasma PAF-AH activity on day 4 (DEX 292+/-5 versus controls 140+/-9 nmol/min/ml, P < 0.001) and day 6 (DEX 302+/-12 versus controls 136+/-6 nmol/min/ml, P < 0.001). Postnatal administration of DEX increases the plasma PAF-AH activity in the rat. Only high doses of prenatal corticosteroids that cause fetal death can elevate maternal plasma PAF-AH activity.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1997

Acute acalculous cholecystitis with a decrease in CD4/CD8 ratio.

Acute acalculous cholecystitis (AAC) usually occurs in the elderly and in those with severe pre-existing pathological conditions. However, there have recently been reports of AAC in relatively young immunosuppressed patients, such as those with acquired immunodeficiency syndrome (AIDS). We report here a 27-year-old woman with AAC who received an emergent cholecystectomy. Although anti-human immunodeficiency virus antibody (anti-HIV) was not detected, a decrease in the CD4/CD8 ratio in sera was found. This rare case of AAC in a patient with decreased CD4/CD8 ratio who showed no other related diseases suggests that surgeons should keep in mind the possible presence of immunosuppression in this condition.

Acute Disease↗
PubMed1997

A new distinctive variation of renal arterial vascularization.

In addition to the usual renal arteries, a bilateral artery branching from the aorta was found connecting the aorta to both kidneys in an 82 year-old Caucasian man. By creating an additional blood supply to the kidneys this artery may have had an effect on renal perfusion.

Aged↗
PubMed1997

Oxidized low-density lipoprotein increases endothelial intracellular calcium and alters cytoskeletal f-actin distribution.

Central to the pathogenesis of atherosclerosis is an abnormally functioning endothelium and a consequent loss of vascular integrity. These abnormalities may be induced by haemodynamic factors, biochemical substances, and also by oxidatively modified low-density lipoprotein (LDL). To understand the mechanism by which oxidized LDL causes endothelial dysfunction, human umbilical vein endothelial cells (HUVECs) were loaded with FURA-2, and intracellular calcium mobilization was studied in acute (seconds after LDL was injected) or chronic (24 h after LDL was injected) preparations. Our results demonstrate that 100 microg mL(-1) oxidized LDL increases HUVEC intracellular calcium. In contrast, native LDL at this same concentration had no effect. In addition, chronic exposure (24 h) of HUVECs to oxidized LDL significantly increases HUVEC intracellular calcium. Fluorescent photomicrographs of HUVECs stained with BODIPY-phalloidin f-actin indicates that oxidized LDL causes a reorganization of microfilaments. The results of this study demonstrate that the mechanism by which oxidized LDL causes a loss of vascular integrity could be through activation of endothelial cells to increase cytosolic calcium, which alters the endothelial barrier by reorganizing the cytoskeleton.

Actins↗
PubMed1997

Renal cell carcinoma of the spindle cell type with metastasis to the pancreas: a case report.

We report a case of renal cell carcinoma in a 49-year-old man with multiple metastases, including some to the pancreas which were initially diagnosed as primary pancreatic carcinoma. The first clinical manifestation was jaundice caused by a large metastatic lymph node. Computed tomography showed tumors in the body and tall of the pancreas as well as in the left kidney. Angiography showed that all of the lesions were hypervascular. The patient was finally diagnosed as having renal cell carcinoma. Cholecystectomy and choledochojejunostomy were performed. Intraoperative biopsy of the lymph nodes along the common hepatic artery showed spindle cell carcinoma which was compatible with renal cell carcinoma. Since renal cell carcinoma with pancreatic metastasis is rare, special attention should be paid to its differentiation from primary pancreatic carcinoma in patients with tumors in both the pancreas and kidneys.

Adrenal Gland Neoplasms↗
PubMed1997

Effects of gamma interferon and nitric oxide on the interaction of Mycobacterium avium subsp. paratuberculosis with bovine monocytes.

In this study, we examined the effects of recombinant bovine gamma interferon (rIFN-gamma) and nitric oxide (NO) on the interaction of M. avium subsp. paratuberculosis with bovine monocytes. Monocytes pretreated with rIFN-gamma exhibited slightly increased phagocytosis of M. avium subsp. paratuberculosis and modest inhibition of the intracellular growth of this microorganism. The number of viable intracellular bacilli decreased earlier in rIFN-gamma-pretreated monocytes than in control monocytes. After infection with M. avium subsp. paratuberculosis, NO was not constitutively released, but NO release from infected monocytes was induced by treatment with rIFN-gamma or with rIFN-gamma and lipopolysaccharide (LPS). Release of nitric oxide was inhibited by addition of N(G)-monomethyl-L-arginine; however, inhibition of nitric oxide did not alter the pattern of intracellular survival of M. avium subsp. paratuberculosis in rIFN-gamma-treated bovine monocytes. Although chemically generated nitric oxide killed M. avium subsp. paratuberculosis in a cell-free system in vitro, the amount of nitric oxide required was far greater than that released from infected monocytes stimulated with rIFN-gamma and LPS. Our data suggest that rIFN-gamma activates M. avium subsp. paratuberculosis-infected bovine monocytes to release nitric oxide but only modestly increases antimycobacterial activity of monocytes against this organism. This may be due, in part, to the fact that the amount of nitric oxide produced by rIFN-gamma-activated bovine monocytes is insufficient to kill intracellular M. avium subsp. paratuberculosis bacilli in vitro.

Animals↗
PubMed1997

Path test reactions to the Chinese Standard Screening Allergens in 1,135 patients investigated for allergic contact dermatitis.

BACKGROUND: The patch test has become the standard method of investigating patients with allergic contact dermatitis. Many countries have developed standard screening allergens to make patch testing more efficient. A series of the Chinese Standard Screening Allergens were studied and modified. OBJECTIVE: This study investigated the frequency of contact allergies in suspected allergic contact dermatitis and tested the practicality of the Chinese Standard Screening Patch Test Allergens. METHODS: A total of 1,135 patients suspected of having allergic contact dermatitis were patch tested. Three hundred twelve (27.5%) were men, and their age ranged from 2 to 75 years old (mean age, 34.3 years), 823 (72.5%) were women, and their age ranged from 2 to 76 years old (mean age, 33.0 years). Nanjing Medical University supplied the Chinese Standard Screening Allergens and Finn-Chamber. All patients were patch tested according to the Chinese Standard Screening Patch Test Allergens with Finn-Chamber the protocol as established by the International Contact Dermatitis Research Group (ICDRG). RESULTS: From the 1,135 patients suspected to have allergic contact dermatitis, 650 (57.3%) had at least one positive reaction. Nineteen (95%) of the Chinese Standard Screening Patch Test Allergens had positive reactions higher than 1%. Of 485 patients with negative reaction to the Standard Allergens, 106 patients were tested with other suspected contactants according to history. Thirty-nine (36.8%) had positive reactions to the contactants they provided. The total positive rate therefore increased by 3.4%. CONCLUSIONS: Our study results indicate that the Chinese Standard Screening Patch Test Allergens are suitable for use in routine clinic in China.

Adolescent↗
PubMed1997

Involvement of activator protein-1 (AP-1) in induction of apoptosis by vitamin E succinate in human breast cancer cells.

The purpose of this study was to document induction of apoptosis by vitamin E succinate (VES; RRR-alpha-tocopheryl succinate) in human breast cancer cells in culture and to characterize potential c-jun involvement. VES at 18.8 microM (10 micrograms/mL) induced DNA synthesis arrest, reduced total cell numbers, and induced apoptosis in estrogen receptor-positive and estrogen-responsive MCF-7 human breast cancer cells. VES at 10 micrograms/mL induced apoptosis in greater than 60% of cells within 3 d of treatment. Apoptosis was documented by detection of fragmented or condensed nuclei in 4',6-diamindino-2-phenylindole-stained cells, detection of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeled DNA, and DNA laddering. Analyses of mRNA and protein levels of candidate molecules involved in apoptosis showed that MCF-7 cells treated with VES exhibited elevated and persistent expression of c-jun. MCF-7 cells stably transfected with a dominant-negative interfering mutant c-jun, TAM-67, and expressing high levels of mutant jun exhibited approximately 50% blockage of VES-mediated apoptosis. In addition to increased c-jun expression after VES treatment, VES-treated MCF-7 cells exhibited elevated activator protein-1 (AP-1) binding activity. Comparisons of AP-1 binding factors by super-shift analyses with jun-specific antibodies in cells sensitive to VES-induced apoptosis (empty-vector control 7-1 cells) and cells resistant to VES-induced apoptosis (TAM-67-containing TAM-9 cells) showed that the sensitive cells expressed c-jun and jun D and the resistant cells TAM-67 AP-1 binding proteins after VES treatment. These studies suggested that c-jun may be involved in the apoptotic process initiated by VES treatment of human MCF-7 breast cancer cells.

Apoptosis↗
PubMed1997

Determinants of plasma platelet-activating factor acetylhydrolase: heritability and relationship to plasma lipoproteins.

Plasma platelet-activating factor acetylhydrolase (PAF-AH) is the enzyme that inactivates PAF (1-alkyl-2-acetyl-sn-glycero-3-phosphocholine). We determined the relative contributions of genetic and environmental factors to variation in plasma PAF-AH activity in 240 individuals from 60 nuclear families. Regression of mean-offspring PAF-AH activity on the mid-parent value indicated that 62% of the variation in plasma PAF-AH activity was heritable. Spousal values were weakly negatively correlated, indicating that familial aggregation of PAF-AH activity is due to genetic rather than to environmental factors. Among normolipidemic individuals, plasma PAF-AH activity was strongly correlated with the plasma concentration of low density lipoprotein cholesterol (LDL-C), and treatment with lovastatin resulted in proportional decreases in plasma PAF-AH activity and LDL-C concentrations. To further elucidate the relationship between PAF-AH and plasma concentrations of LDL, plasma PAF-AH activity was measured in families with well-defined, monogenic disorders of LDL metabolism. Plasma PAF-AH activity cosegregated with plasma LDL-C concentrations in familial hypercholesterolemia, but not in familial hypobetalipoproteinemia. We speculate that the rate of removal of LDL from the circulation may determine the clearance rate of PAF-AH, thereby modulating the activity of PAF-AH in blood.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1997

[Impact of nitric oxide on endothelin gene expression in intrapulmonary arteries of chronic hypoxic rats].

OBJECTIVE: To investigate the impact of nitric oxide on endothelin-1 (ET-1) mRNA expression in pulmonary artery endothelial cells and pulmonary artery smooth muscle cells of chronic hypoxic rats. METHODS: In situ hybridization was performed on lung sections from 40 chronic hypoxic rats treated either with L-Arginine (L-Arg) or N omega-nitro-L-arginine methyl ester (L-NAME) by using cRNA probe for ET-1. RESULTS: Most intrapulmonary arteries had 1%-50% of the endothelial cells expressing ET-1 mRNA in both one-week and two-week hypoxic rats (75% +/- 3% and 71% +/- 6%, respectively), which was significantly inhibited by L-Arg but augmented by L-NAME administration. Most pulmonary artery smooth muscle cells showed no ET-1 mRNA signals in both one-week and two-week hypoxic rats (85% +/- 6% and 98% +/- 2%, respectively). However, L-NAME increased ET-1 mRNA expression in pulmonary artery smooth muscle cells of hypoxic rats. CONCLUSION: Nitric oxide inhibited ET gene expression in both pulmonary artery endothelial cells and smooth muscle cells of rats exposed to chronic hypoxia.

Animals↗
PubMed1996

Studies on protective mechanisms of four components of green tea polyphenols against lipid peroxidation in synaptosomes.

The comparison of the protective effects of four components of "green tea polyphenols' (GTP) - (-)-epigallocatechin gallate, EGCG; (-)-epicatechin gallate, ECG; (-)epigallocatechin, EGC; and (-)epicatechin, EC - against iron-induced lipid peroxidation in synaptosomes showed that: (1) the inhibitory effects of those compounds on TBA reactive materials from lipid peroxidation decreased in the order of EGCG > ECG > EGC > EC; (2) the scavenging effects of those compounds on lipid free radicals produced by lipid peroxidation could be classified as follows: ECG > EGCG > EC > EGC. Furthermore, we investigated the iron-chelating activity and the free radical scavenging activity of those compounds as their protective mechanisms against lipid peroxidation in synaptosomes. As for the iron-chelating activity, the ratio of EGC, EGCG, ECG or EC to iron(III) was 3:2, 2:1, 2:1 and 3:1, respectively. The hydroxyl radical (HO) scavenging activity of those compounds was investigated in a photolysis of the H2O2 system. It was found that their ability to scavenge hydroxyl radicals decreased in the order of ECG > EC > EGCG >> EGC. It was also found that they could scavenge lipid free radicals in the lecithin/lipoxidase system and their scavenging activity was classified as follows: ECG > EGCG >> EGC > EC. Moreover, we found that their antioxidant active positions were different from each other and the stability of the semiquinone free radicals produced by those compounds in NaOH solution decreased in the order of EGCG > ECG >> EC. The results indicated that the ability of those compounds to protect synaptosomes from the damage of lipid peroxidation initiated by Fe2+/Fe3+ was dependent not only on their iron-chelating activity and free-radical scavenging activity, but also on the stability of their semiquinone free radicals.

Animals↗