Biomedical subjects

C Hao

Publications and source records attributed to C Hao.

At least 19 recordsLinked to original sources

PubMed2006

A double-blind, placebo-controlled study of house dust mite immunotherapy in Chinese asthmatic patients.

BACKGROUND: The purpose of this study was to determine if house dust mite immunotherapy with Alutard SQ is effective in improving symptom control and reducing rescue medication use in Chinese patients with mild to moderate allergic asthma. METHODS: This is a double-blind, placebo-controlled study involving 132 asthmatic subjects aged 6-45 years recruited from three different regions of Mainland China. Subjects were given a 52-week course of immunotherapy with Dermatophagoides pteronyssinus extract (Alutard Der p, ALK-Abelló, Hørsholm, Denmark) or placebo while their dose of inhaled corticosteroids (ICS) was maintained. RESULTS: 129 subjects (64 in active group) completed the study. The symptom scores began to diverge at week 29 with the immunotherapy group showing a significantly lower score until week 48 (P = 0.018). Immunotherapy resulted in a significant decline in symptom (P = 0.002) and medication (P = 0.007) scores during the second half of the treatment period. Both groups showed significant improvement in peak flow rate and bronchial hyperresponsiveness. Serum eosinophil cationic protein (ECP) also decreased in both groups of subjects, but peripheral blood eosinophil count remained unchanged. Skin test response decreased in actively treated subjects only, but Der p-specific immunoglobulin E (IgE) remained unchanged. Immunotherapy resulted in a significantly greater improvement in self-evaluation scores (P < 0.01). CONCLUSIONS: One year treatment with Alutard SQ house dust mite immunotherapy significantly reduced symptoms and medication use in asthmatic subjects. This was associated with a greater subjective improvement in asthma control.

Adolescent↗

PubMed2005

Cyclin-dependent kinase-5 prevents neuronal apoptosis through ERK-mediated upregulation of Bcl-2.

Cyclin-dependent kinase-5 (Cdk5) is required for neuronal survival, but its targets in the apoptotic pathways remain unknown. Here, we show that Cdk5 kinase activity prevents neuronal apoptosis through the upregulation of Bcl-2. Treatment of SH-SY5Y cells with retinoid acid (RA) and brain-derived neurotrophic factor (BDNF) generates differentiated neuron-like cells. DNA damage triggers apoptosis in the undifferentiated cells through mitochondrial pathway; however, RA/BDNF treatment results in Bcl-2 upregulation and inhibition of the mitochondrial pathway in the differentiated cells. RA/BDNF treatment activates Cdk5-mediated PI3K/Akt and ERK pathways. Inhibition of Cdk5 inhibits PI3K/Akt and ERK phosphorylation and Bcl-2 expression, and thus sensitizes the differentiated cells to DNA-damage. Inhibition of ERK, but not PI3K/Akt, abrogates Cdk5-medidated Bcl-2 upregulation and the protection of the differentiated cells. This study suggests that ERK-mediated Bcl-2 upregulation contributes to BDNF-induced Cdk5-mediated neuronal survival.

Apoptosis↗

PubMed2005

Aberrant methylation of SPARC in human lung cancers.

SPARC (secreted protein acidic and rich in cysteine) is an extracellular Ca2+-binding matricellular glycoprotein associated with the regulation of cell adhesion and growth. We investigated loss of expression of SPARC gene and promoter methylation in lung cancers and correlated the data with clinicopathological features. We observed loss of SPARC expression in 12 of 20 (60%) lung cancer cell lines. Treatment of expression-negative cell lines with a demethylating agent restored expression in all cases. Methylation frequencies of SPARC gene were 55% in 20 lung cancer cell lines. Primary tumours had methylation at a rate of 69% (119 of 173), while nonmalignant lung tissues (n=60) had very low rates (3%). In lung adenocarcinomas, SPARC methylation correlated with a negative prognosis (P=0.0021; relative risk 4.65, 95% confidence interval 1.75-12.35, multivariate Cox's proportional-hazard model). Immunostaining revealed protein expression in bronchial epithelium (weak intensity) and in juxtatumoral stromal tissues (strong intensity) accompanied by frequent loss in cancer cells that correlated with the presence of methylation (P<0.001). Our findings are of biological interest and potentially of clinical importance in human lung cancers.

Adenocarcinoma↗

PubMed2004

Abbreviated course of radiation therapy in older patients with glioblastoma multiforme: a prospective randomized clinical trial.

PURPOSE: To prospectively compare standard radiation therapy (RT) with an abbreviated course of RT in older patients with glioblastoma multiforme (GBM). PATIENTS AND METHODS: One hundred patients with GBM, age 60 years or older, were randomly assigned after surgery to receive either standard RT (60 Gy in 30 fractions over 6 weeks) or a shorter course of RT (40 Gy in 15 fractions over 3 weeks). The primary end point was overall survival. The secondary end points were proportionate survival at 6 months, health-related quality of life (HRQoL), and corticosteroid requirement. HRQoL was assessed using the Karnofsky performance status (KPS) and Functional Assessment of Cancer Therapy-Brain (FACT-Br). RESULTS: All patients had died at the time of analysis. Overall survival times measured from randomization were similar at 5.1 months for standard RT versus 5.6 months for the shorter course (log-rank test, P =.57). The survival probabilities at 6 months were also similar at 44.7% for standard RT versus 41.7% for the shorter course (lower-bound 95% CI, -13.7). KPS scores varied markedly but were not significantly different between the two groups (Wilcoxon test, P =.63). Low completion rates of the FACT-Br (45%) precluded meaningful comparisons between the two groups. Of patients completing RT as planned, 49% of patients (standard RT) versus 23% required an increase in posttreatment corticosteroid dosage (chi(2) test, P =.02). CONCLUSION: There is no difference in survival between patients receiving standard RT or short-course RT. In view of the similar KPS scores, decreased increment in corticosteroid requirement, and reduced treatment time, the abbreviated course of RT seems to be a reasonable treatment option for older patients with GBM.

Adrenal Cortex Hormones↗

PubMed2003

Pediatric temporal lobectomy for epilepsy.

BACKGROUND: Temporal lobectomy in adults is an accepted form of treatment for patients with intractable complex partial seizures. There have been few long-term studies of children undergoing temporal lobectomy for epilepsy. METHODS: We reviewed the pediatric cases of temporal lobectomy for intractable epilepsy performed by the Comprehensive Epilepsy Program at the University of Alberta Hospitals between 1988 and 2000. All patients had preoperative and postoperative clinical evaluations, seizure charts, drug levels, EEG, CT/MRI, long-term video EEG monitoring and neuropsychological testing. The patients were reassessed at 6 weeks, 6 months and 1 year postoperatively, then yearly. The duration of follow up was 1-10 years (mean 5 years). RESULTS: Forty-two patients were studied (25 males and 17 females). Age at surgery ranged from 18 months to 16 years. The interictal EEG was abnormal in 38 of the 42 patients. Twenty-two patients had focal epileptic discharge and 1 had generalized epileptic discharge. Focal slowing was seen in 9 patients and diffuse slowing in 5 patients. CT scan was abnormal in 17 of 39 patients and normal in 22 of 39. MRI was abnormal in 34 of 42 patients and normal in 8 of 42. Pathology included brain tumors in 14 patients, mesial temporal sclerosis in 8, focal cortical dysplasia in 4, tuberous sclerosis in 4, dual pathology in 4, porencephalic cyst in 1 and normal pathology or gliosis in 6. Thirty-three of 42 patients (78%) were seizure-free following surgery and an additional 5 (12%) had a decrease in seizure frequency. Three patients had complications, but there were no deaths. CONCLUSION: Temporal lobectomy is a safe and effective treatment for children with intractable complex partial seizures. Seventy-eight percent of patients are seizure-free following the surgery and there are few complications. MRI is superior to CT scan for detection of temporal lobe pathology yet failed to detect abnormalities in some patients. The most common pathologies found were brain tumors, mesial temporal sclerosis and developmental lesions. In addition to seizure control, many patients experienced improvement in cognitive and psychosocial function following surgery.

Adolescent↗

PubMed2001

Sequestration and phosphorylation of the prostaglandin E2 EP4 receptor: dependence on the C-terminal tail.

The prostaglandin E2 (PGE2) EP4 subtype is one of four prostanoid receptors that use PGE2 as the preferred ligand. We have investigated the agonist-mediated regulation of EP4 using a multifaceted approach. Short-term (30 min) agonist challenge of recombinant EP4 expressed in human embryonic kidney 293 cells (EP4-HEK293 cells) with PGE2 (1 microM) resulted in the desensitization of intracellular cyclic AMP (cAMP) accumulation and a reduction in cell surface [3H]PGE2 specific binding sites. These events correlated with sequestration of EP4, as visualized by immunofluorescence confocal microscopy and phosphorylation, as shown by [32P]orthophosphate labeling of the receptor. Stimulation of protein kinase A activity in EP4-HEK293 cells (10 microM forskolin or 1 mM 8-bromo-cAMP) did not induce EP4 desensitization, sequestration, or phosphorylation. In contrast, stimulation of protein kinase C activity (100 nM phorbol 12-myristate 13-acetate) attenuated PGE2-induced adenylyl cyclase activity and increased EP4 phosphorylation, but did not induce sequestration or a reduction in [3H]PGE2 specific binding sites. EP4 receptors containing a third intracellular loop deletion [EP4 (del. 215-263)] or a carboxyl-terminal tail truncation [EP4 (del. 355)] of EP4 were used to demonstrate that the C-terminal tail governs sequestration as well as phosphorylation of the receptor.

Amino Acid Sequence↗

PubMed2001

Ultraviolet light (UV) regulation of the TNF family decoy receptors DcR2 and DcR3 in human keratinocytes.

BACKGROUND: Several additional members of the tumor necrosis factor (TNF) receptor family were recently identified. The existence of such receptors, which may play distinct and unique regulatory roles, suggests that complex regulatory mechanisms are involved in apoptosis. OBJECTIVE: This study examines the expression of several members of the TNF receptor family in human keratinocytes exposed to ultraviolet B (UVB) irradiation. METHODS: Human keratinocytes were exposed to increasing doses of UVB, total RNA was harvested, and a quantitative RNase protection assay was performed. RESULTS: Decoy receptor-3 (DcR3), a nonfunctional receptor that binds to Fas ligand (FasL), was constitutively expressed at high level in keratinocytes but decreased rapidly in cells exposed to UVB. Decoy receptor-2 (DcR2), a nonfunctional receptor that binds to TNF-related apoptosis-inducing ligand (TRAIL)/APO-2L, showed the opposite expression pattern. DcR2 was undetectable in unirradiated keratinocytes and was markedly up-regulated after exposure to UVB. Although the response showed significant delays at higher UVB doses, the patterns observed for DcR3 and DcR2 were consistent in this set of experiments. CONCLUSION: We conclude that UVB regulates expression of these two TNF decoy receptors in keratinocytes. This pathway may represent a novel mechanism for regulation of apoptosis in the skin.

Apoptosis↗

PubMed2001

[Analgesic effect of neurolytic celiac plexus block guided by ultrasonography in advanced malignancies].

OBJECTIVE: To investigate the analgesic effect of celiac plexus block with anhydrous alcohol in patients suffering form advanced abdominal malignancies. METHODS: Ultrasonographically demonstrated and guided, 20 to 50 ml of anhydrous alcohol is injected into the celiac plexus and superior mesenteric plexus by fine needle of 22G. The injecting angle between the needle and the aorta is 20 to 30 degree. The injecting fields mainly located around the celiac plexus and the dorsal part of tumor are also injected. Sometimes if the tumor is rather large, an appropriate amount of alcohol was injected inside too. RESULTS: Twenty-eight cases of advanced abdominal malignancies were treated, among whom 96.4% achieved analgesic effect of different degree, 53.6% (15 cases) achieved the period of pain relief over three days, and 42.8% (12 cases) achieved partial relief. The analgesic effect is correlated with the amount of alcohol injected, i.e. no complete relief was observed in the four patients who received less than 12 ml, while two out of six could get transient complete relief in those who received 15 to 28 ml. In the group of 30 to 50 ml, 72.2% (13 cases) could get complete pain relief. Nine cases with big tumor received injection in side the tumor, with six tumors resulting in shrinkage or necrosis, significant pain relief also achieved in these cases. Complications occurred in nine cases (32.1%), with four cases of postural hypotension, two cases of vomiting, two cases of hiccup and one case of diarrhea. CONCLUSION: Neurolytic celiac plexus block guided by ultrasonography is a safe and effective modality in the management of intractable pain resulted from advanced abdominal malignancies.

Abdominal Neoplasms↗

PubMed2001

Induction and intracellular regulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mediated apotosis in human malignant glioma cells.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) preferentially triggers apoptosis in tumor cells versus normal cells, thus providing a therapeutic potential. In this study, we examined a large panel of human malignant glioma cell lines and primary cultures of normal human astrocytes for their sensitivity to TRAIL. Of 13 glioma cell lines, 3 were sensitive (80-100% death), 4 were partially resistant (30-79% death), and 6 were resistant (< 30% death). Normal astrocytes were also resistant. TRAIL-induced cell death was characterized by activation of caspase-8 and -3, poly(ADP-ribose) polymerase cleavage, and DNA fragmentation. Decoy receptor (DcR1 and DcR2) expression was limited in the glioma cell lines and did not correlate with TRAIL sensitivity. Both sensitive and resistant cell lines expressed TRAIL death receptor (DR5), adapter protein Fas-associated death domain (FADD), and caspase-8; but resistant cell lines expressed 2-fold higher levels of the apoptosis inhibitor phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes-15 kDa (PED/PEA-15). In contrast, cellular FADD-like IL-1beta-converting enzyme-like inhibitory protein (cFLIP) expression was similar in sensitive and resistant cells. Transfection of sense PED/PEA-15 cDNA in sensitive cells resulted in cell resistance, whereas transfection of antisense in resistant cells rendered them sensitive. Inhibition of protein kinase C (PKC) activity restored TRAIL sensitivity in resistant cells, suggesting that PED/ PEA-15 function might be dependent on PKC-mediated phosphorylation. In summary, TRAIL induces apoptosis in > 50% of glioma cell lines, and this killing occurs through activation of the DR pathway. This caspase-8-induced apoptotic cascade is regulated by intracellular PED/PEA-15, but not by cFLIP or decoy receptors. This pathway may be exploitable for glioma and possibly for other cancer therapies.

Apoptosis↗

PubMed2001

Electrospray ionization tandem mass spectrometric study of salt cluster ions. Part 1--investigations of alkali metal chloride and sodium salt cluster ions.

Salt cluster ions of alkali metal chlorides ACl (A = Li(+), Na(+), K(+), Rb(+) and Cs(+)) and sodium salts NaB (B = I(-), HCOO(-), CH(3)COO(-), NO(2)(-), and NO(3)(-)), formed by electrospray ionization, were studied systematically by mass spectrometry. The influences on the total positive ion and negative ion currents of variation of solvent, solution concentration, desolvation temperature, solution flow-rate, capillary voltage and cone voltage were investigated. Only cone voltage was found to influence dramatically the distribution of salt cluster ions in the mass spectra observed. Under conditions of normal cone voltage of approximately 70 V, cluster ions having magic numbers of molecules are detected with high relative signal intensity. Under conditions of low cone voltage of approximately 10 V, the distribution of cluster ions detected is characterized by a relatively low average mass/charge ratio due to the presence of multiply charged cluster ions; in addition, there is a marked reduction in cluster ions having a magic number of molecules. Product ion mass spectra obtained by tandem mass spectrometry of cluster ions are characterized by a base peak having a magic number of molecules that is less than and closest to the number of molecules in the precursor ion. Structures have been proposed for some dications and some quadruply charged ions. At pH 3 and 11, the mass spectra of NaCl clusters show the presence of mixed clusters of NaCl with HCl and NaOH, respectively. The effects of ionic radius on 20 distributions of cluster ions for 10 salts were investigated; however, the fine structure of these effects is not readily discerned.

Journal Article↗

PubMed2001

Electrospray ionization tandem mass spectrometric study of salt cluster ions: part 2--salts of polyatomic acid groups and of multivalent metals.

Salt cluster ions formed from 0.05 M solutions of CaCl(2), CuCl(2) and Na(A)B (where A = 1 or 2 and B = CO(3)(2-), HCO(3)(-), H(2)PO(4)(-) and HPO(4)(2-)) were studied by electrospray ionization tandem mass spectrometry. The effects on salt cluster ions of droplet pH and of redox reactions induced by electrospray provide information on the electrospray process. CaCl(2) solution yielded salt cluster ions of the form (CaCl(2))(n)(CaCl)(x)(x+) and (CaCl(2))(n)(Cl)(y)(y-), where x, y = 1-3, in positive- and negative-ion modes, respectively. Upon collision induced dissociation (CID), singly charged CaCl(2) cluster ions fragmented, doubly charged cluster ions generated either singly or both singly and doubly charged fragment ions, depending on the cluster mass, and triply charged clusters fragmented predominantly by the loss of charged species. CuCl(2) solution yielded nine series of cluster ions of the form (CuCl(2))(n)(CuCl)(m) plus Cu(+), CuCl(+), or Cl(-). CuCl, the reductive product of CuCl(2), was observed as a neutral component of positively and negatively charged cluster ions. Free electrons were formed in a visible discharge that bridged the gap between the electrospray capillary and the sampling cone brought about the reduction of Cu(2+) to Cu(+). Upon CID, these cluster ions fragmented to lose CuCl(2), CuCl, Cl, and Cl(2). Na(2)CO(3) and NaHCO(3) solutions yielded cluster ions of the form (Na(2)CO(3))(n) plus Na(+) or NaCO(3)(-). Small numbers of NaHCO(3) molecules were found in some cluster ions obtained with the NaHCO(3) solution. For both Na(2)HPO(4) and NaH(2)PO(4) solutions, ions of the form (Na(2)HPO(4))(h), (NaH(2)PO(4))(i), (Na(3)PO(4))(j), (NaPO(3))(k) plus Na(+), PO(3)(-) or H(2)PO(4)(-) were observed. In addition, ions having one or two phosphoric acid (H(3)PO(4)) molecules were observed from the NaH(2)PO(4) solution while ions containing one sodium hydroxide (NaOH) molecule were observed from the Na(2)HPO(4) solution. The cluster ions observed from these four salts of polyatomic acid groups indicate that changes in pH occur in both directions during the electrospray process principally by solvent evaporation; the pH value of the acidic solution became lower and that of the basic solution higher.

Journal Article↗

PubMed2001

Distinct regional distribution of human equilibrative nucleoside transporter proteins 1 and 2 (hENT1 and hENT2) in the central nervous system.

Nucleoside transport processes play an important role in human cells in salvage of nucleosides used in the biosynthesis of nucleic acids and in regulating endogenous adenosine concentrations in the human central nervous system (CNS). By altering the levels of adenosine available to interact with cell-surface receptors, nucleoside transporters have profound effects on the ability of adenosine to modulate neurotransmission, vascular tone and other physiological events. Although the human equilibrative nucleoside transporters 1 and 2 (hENT1 and hENT2) are believed to play a crucial role in modulating brain function, their distribution within the major divisions of the human CNS is not known. In this work, antibodies specific for hENT1 and hENT2 were produced against fragments of the transporter proteins and used for immunoblot analysis of enriched membrane fractions prepared from several regions of the human brain. While hENT1 was most prevalent in the frontal and parietal lobes of the cerebral cortex, thalamus, midbrain and basal ganglia, hENT2 was concentrated in the cerebellum and brainstem regions, particularly the pons. The apparent reciprocal distribution of hENT1 and hENT2 in human brain suggests that these nucleoside transporter proteins are produced in distinct regions of the CNS where they function in nucleoside salvage and/or regulation of exogenous adenosine. Within the brain regions that were investigated, the pattern of hENT1 distribution correlated well with adenosine A(1) receptor abundance. The regional co-localization of hENT1 and A(1) receptor protein suggests an important role of hENT1-mediated transport process in the control of neuromodulatory actions mediated by adenosine A(1) receptors in human brain.

Adenosine↗

PubMed2001

Hepatitis C virus replication in mice with chimeric human livers.

Lack of a small animal model of the human hepatitis C virus (HCV) has impeded development of antiviral therapies against this epidemic infection. By transplanting normal human hepatocytes into SCID mice carrying a plasminogen activator transgene (Alb-uPA), we generated mice with chimeric human livers. Homozygosity of Alb-uPA was associated with significantly higher levels of human hepatocyte engraftment, and these mice developed prolonged HCV infections with high viral titers after inoculation with infected human serum. Initial increases in total viral load were up to 1950-fold, with replication confirmed by detection of negative-strand viral RNA in transplanted livers. HCV viral proteins were localized to human hepatocyte nodules, and infection was serially passaged through three generations of mice confirming both synthesis and release of infectious viral particles. These chimeric mice represent the first murine model suitable for studying the human hepatitis C virus in vivo.

Animals↗

PubMed2001

Expression and localization of cyclin-dependent kinase 5 in apoptotic human glioma cells.

Cyclin-dependent kinase 5 (Cdk5), a member of the cyclin-dependent kinase family, is expressed predominately in mature neurons and is implicated in neurite extension, neuronal migration, and neuronal differentiation. Cdk5 protein expression also has been associated with apoptosis in a number of nonneuronal model systems. In normal brain, substrates for Cdk5 include neurofilament and tau proteins. Because human tumors of glial origin can express neuronal proteins, we examined whether Cdk5 and its activator protein, P35, are present in early passage human glioblastoma multiforme (GBM) cells lines and primary tumor specimens. Here we report the expression of Cdk5 and an "active" proteolytic form of P35 in human GBM cells and demonstrate kinase activity of the holoenzyme. We also show that Cdk5 kinase activity and expression of its activator protein, P35, is increased in the human GBM cell line M059J after exposure to ionizing radiation and that P35 is localized within M059J cells undergoing apoptosis. These results suggest a possible role for Cdk5 in mediating apoptosis in human GBM cells.

Apoptosis↗

PubMed2001

Cyclooxygenase-2 selective inhibitors and the kidney.

Cyclooxygenases (COX) are the target of non-steroidal anti-inflammatory drugs (NSAIDs) which exert their therapeutic effect by blocking COX's capacity to metabolize arachidonate to a series of biologically active fatty acids, designated prostaglandins. NSAID use is associated with two major tonicities: gastrointestinal bleeding and renal dysfunction. In the setting of significant physiologic stress, renal function becomes dependent upon prostaglandins and NSAID use may be associated with acute deterioration of renal function, including development of sodium retention, edema, hypertension, hyperkalemia, and or papillary necrosis. Two isoforms, COX1 and COX2, have been identified. They are products of distinct genes and their expression is under different regulatory control. Both COX1 and COX2 are highly expressed in the kidney and both are inhibited by conventional NSAIDs. Accumulating data using recently developed selective COX2 inhibitors suggest that while these agents spare the gastrointestinal tract they have similar renal effects as non-selective NSAIDs. Therefore, caution should be taken when prescribing selective COX2 inhibitor to patients, especially to patients with predisposed physiologic stress.

Animals↗

PubMed2001

Pathology and neuroimaging in pediatric temporal lobectomy for intractable epilepsy.

OBJECTIVES: Firstly, to study the pathology at surgery in children undergoing temporal lobectomy for intractable partial epilepsy. Secondly, to compare neuroimaging techniques (CT, MRI) in the preoperative detection of pathology. Lastly, to examine the surgical outcome in children. METHODS: Forty-two pediatric patients undergoing temporal lobectomy for intractable epilepsy at the Comprehensive Epilepsy Program at the University of Alberta Hospital between the years 1988-1998 were studied. Patients had extensive preoperative investigations including CT and MRI. The pathology at surgery was reviewed and compared to preoperative neuroimaging. Charts were reviewed to determine surgical outcome. RESULTS: Brain tumors were the most common pathology, found in 13/42 patients. Mesial temporal sclerosis (MTS) was found in 8 patients and dual pathology in an additional 5. Focal cortical dysplasia (FCD) was seen in 4 patients, 1 patient had a porencephalic cyst and 4 patients had tubers of tuberous sclerosis. Seven patients had no specific pathology detected. MRI was clearly more sensitive than CT in the detection of pathology. MRI was abnormal in 27/42 cases (64%), while CT scan was found to be abnormal in only 12/39 (31%). Surgical outcome was excellent, with 34/42 patients (80%) having an Engel class I outcome. One patient had significant improvement with an Engel class II outcome, 3 (7%) had little improvement (Engel class III) and 4 (10%) were unchanged (Engel class IV). Three patients (7%) had surgical complications. CONCLUSIONS: A wide variety of developmental pathology is seen following temporal lobectomy for intractable epilepsy of childhood. Brain tumors, FCD and MTS are common. MRI is superior to CT in the detection of pathology, which may be subtle in children. Surgical outcome is excellent, with most children being seizure free and few complications being seen.

Adolescent↗

PubMed2001

Effect of radiation on cytokine and cytokine receptor messenger-RNA profiles in p53 wild and mutated human glioblastoma cell lines.

OBJECTIVE: Glioblastoma cells produce cytokines with proinflammatory or immunosuppressive properties, or both, which, in addition to altered p53 gene expression, have been shown to be associated with glioblastoma resistance to radiotherapy. The reported data concerning cytokines have been isolated and sometimes discordant, and a comprehensive profile analysis of cytokines and their corresponding receptors in irradiated glioblastomas has received limited attention. The object of this study was to test the hypothesis that radiation alone in clinically relevant doses would not significantly alter expression of endogenous cytokines and their receptors in human glioblastoma celll ines with wild-type and mutant p53. DESIGN AND METHOD: Culture specimens of 4 glioblastoma cell lines of different p53 gene expression (U87, U118, U251, U373) were irradiated with cobalt 60 at a dose of 10 Gy. After 48 hours, radiosensitivity was defined through a colony formation assay, cell cycle distribution was analyzed by flow cytometry, and cytokine and cytokine receptor messenger-RNA (mRNA) profiles were defined with an RNase protection assay. Different single doses of radiation at varying time intervals after culture were applied also to wild-type p53 cell lines. RESULTS: All cell lines were relatively radioresistant at lower doses of 1 and 2 Gy. Immunosuppressive cytokine and cytokine receptor mRNA of the Th2 (IL-13Ralpha, IL-4) and Th3 family (TGF-beta1, 2 and 3, TGF-betaRI and RII) were expressed. In contrast, only 2 proinflammatory Th1 cytokine receptor genes (IFN-gammaRa and IFN-gammaRbeta), but no significant Th1 cytokine gene expression, were detected. Even though the population examined included a large fraction of reproductively dead cells, cytokine and cytokine receptor mRNA profiles were not altered significantly by irradiation in all cell lines, regardless of the p53 status. CONCLUSION: These results suggest that cobalt irradiation alone at clinically relevant doses does not significantly alter the cytokine and cytokine receptor profiles in human glioblastoma cell lines.

Cobalt Radioisotopes↗

PubMed2001

[The research of pancadherin and beta-catenin expression in pulmonary tissue of mice with bleomycin-induced pulmonary fibrosis].

OBJECTIVE: To investigate the changes of pancadherin(Pan-cd) and beta-catenin(beta-cat) expression in pulmonary tissue of mice with bleomycin (BLM)-induced pulmonary injury and explore the relation between the Pan-cd/beta-cat expression and pulmonary fibrosis. METHOD: A single dose of BLM was intratracheally injected to induce pulmonary fibrosis of mice. Animals were killed and immunohistochemical methods were used with polyclonal anti-Pan-cd and anti-beta-cat antiserum. RESULTS: The expression of Pan-cd in type I alveolar cells was down-regulation. The expression of Pan-cd in type II alveolar cells was induced. The expression of Pan-cd and beta-cat in small airway epithelial cells were all down-regulation and were repeated with the way of down-regulation-reparation-down-regulation. The expression of Pan-cd on membrane in small airway epithelial cells decreased, whereas the cytoplasmic expression increased and was repeatedly alternated between cytoplasma with membrane. The expression of Pan-cd in alveolar macrophage and interstitial cells increased. CONCLUSION: The abnormal expression of cadherin and beta-cat may play a role in the pathogenesis of pulmonary fibrosis after pulmonary injury.

Animals↗