Biomedical subjects

Q Liao

Publications and source records attributed to Q Liao.

At least 19 recordsLinked to original sources

PubMed2006

Levosimendan cardioprotection reduces the metabolic response during temporary regional coronary occlusion in an open chest pig model.

BACKGROUND: Inotropic and myocardial anti-ischemic effects have been demonstrated with levosimendan. The comparison of levosimendan started before an ischemia-reperfusion event as compared with levosimendan started during ischemia has not been studied. METHODS: In anesthetized pigs, a major branch of the circumflex artery was completely occluded for 30 min and then reperfused. The metabolism in the ischemic myocardium and in non-ischemic control myocardium was studied with microdialysis concomitantly with monitoring of global hemodynamics and coronary artery flow in the chosen artery. In the protection group (PRO, n= 6), a levosimendan infusion was started 30 min before coronary artery occlusion, and in the treatment group (TRE, n= 6), a levosimendan infusion was started 10 min after the coronary artery occlusion with a loading dose of 13.3 microg/kg followed by an infusion of 0.67 microg/kg/min. A two-way repeated measures ANOVA completed with Bonferroni's multiple comparison procedure was applied to the data. A P < 0.05 was considered significant. RESULTS: During the ischemic period, the cardiac output and contractility (dp/dt(max)) were higher in the PRO as compared with the TRE and the systemic vascular resistance was lower. The myocardial microdialysate glucose concentration in the ischemic area during ischemia was higher in the PRO as compared with the TRE, and the lactate/pyruvate ratio and the lactate concentration were lower. The differences in the metabolites persisted into the first 10 min of reperfusion. No differences were found for the non-ischemic areas. CONCLUSION: Levosimendan used throughout myocardial ischemia-reperfusion might have a cardioprotective affect on the response to myocardial ischemia as compared with levosimendan started during the ischemia.

Animals↗

PubMed2006

Myocardial glycerol release, arrhythmias and hemodynamic instability during regional ischemia-reperfusion in an open chest pig model.

BACKGROUND: To develop cardioprotection against peri-operative myocardial ischemia-reperfusion injury, we need animal models where the local metabolism and blood flow are studied concomitantly with the global circulatory consequences during regional coronary occlusion. METHODS: In six anesthetized domestic pigs, the largest branch of the circumflex artery was occluded for 30 min. Microdialysate was sampled from the ischemic and non-ischemic myocardium along with continuous measurements of local coronary artery flow, global hemodynamics and registration of arrhythmias, from baseline through to 30 min of ischemia and 180 min of reperfusion. RESULTS: During ischemia, the microdialysate glucose concentration decreased, the glycerol concentration increased and the lactate/pyruvate ratio increased significantly. For glycerol, there was a further increase at reperfusion. During ischemia, cardiac output was unchanged; however, during reperfusion there was a significant drop lasting for several minutes, longer than the period in which an increased number of arrhythmias were registered. CONCLUSION: The present study demonstrates deranged circulation and arrhythmias corresponding to ischemic metabolism after regional myocardial ischemia and reperfusion. Reperfusion induced more pronounced circulatory changes than the actual ischemia. A substantial increase in myocardial glycerol release seems to be a marker of ischemic metabolism and may prove to be an indicator of reperfusion injury.

Animals↗

PubMed2005

Two cis-acting elements in negative RNA strand of Hepatitis C virus involved in synthesis of positive RNA strand in vitro.

Sequences at the 3'-ends of both positive and negative strands of Hepatitis C virus (HCV) RNA harbor cis-acting elements required for RNA replication. However, little is known about the properties of the negative RNA strand as a template for the synthesis of positive RNA strand. In this study, a purified recombinant HCV RNA-dependent RNA polymerase (RdRp) was used to investigate the synthesis of positive RNA strand using the 3'-terminal region of negative RNA strand ((-)3'T RNA) as template. A mutagenesis analysis was performed to evaluate the role of the 3'-proximal stem-loop and the first 3'-cytidylate (3'C) of the negative RNA strand in the synthesis of the positive RNA strand. A negative RNA strand of wild type (wt) HCV as template was able to direct the synthesis of a full-length positive RNA strand. Deletion of the 3'-proximal stem-loop resulted in an approximately 90% decrease in RNA synthesis. Disruption of the 3'-proximal stem-loop structure by nucleotide substitutions led to a 70-80% decrease in RNA synthesis. However, the restoration of the stem-loop by compensatory mutations in the stem region restored also the RNA synthesis. Likewise, the deletion or substitution of the first 3'C by guanylate (G) led to a 90% decrease in the RNA synthesis; while the substitution by adenylate (A) or uridylate (U) resulted in a 60-80% decrease in the RNA synthesis only. These findings demonstrate that the 3'-proximal stem-loop and the first 3'C of the negative RNA strand of HCV are two cis-acting elements involved in the synthesis of the positive RNA strand.

3' Untranslated Regions↗

PubMed2004

CISOC-PSCT: a predictive system for carcinogenic toxicity.

A SAR based carcinogenic toxicity prediction system, CISOC-PSCT, was developed. It consisted of two principal phases: the construction of relationships between structural descriptors and carcinogenic toxicity indices, and prediction of the toxicity from the SAR model. The training set included 2738 carcinogenic and 4130 non-carcinogenic compounds. Three predefined topological types of substructures termed Star, Path and Ring were used to generate the descriptors for each structure in the training set. In this system, the defined carcinogenic toxicity index (CTI) was obtained from the probability of a structural descriptor to either belong to the carcinogenic or non-carcinogenic compounds. Based on these structural descriptors and their CTI, a SAR model was derived. Then the carcinogenic possibility (CP) and the carcinogenic impossibility (CIP) of compounds were predicted. The model was tested from a testing set of 304 carcinogenic compounds (MDL toxicity database), 460 non-carcinogenic compounds (CMC database) and 94 compounds extracted from two traditional Chinese medicine herbs.

Carcinogens↗

PubMed2003

COMP is selectively up-regulated in degenerating acinar cells in chronic pancreatitis and in chronic-pancreatitis-like lesions in pancreatic cancer.

BACKGROUND: Chronic pancreatitis (CP) is an inflammatory disease of the pancreas characterized histomorphologically by progressive development of fibrosis and atrophy of the pancreatic parenchyma. Cartilage oligomeric matrix protein (COMP) is a member of the thrombospondin (TSP) family of extracellular glycoproteins that is expressed in CP tissues. In the present study, we characterized COMP mRNA and protein expression in the normal pancreas, chronic pancreatitis, and pancreatic cancer tissues. METHODS: 15 normal pancreatic tissues, 14 CP tissues and 14 pancreatic cancer tissues were analyzed by Northern blotting, Western blotting, in situ hybridization and immunohistochemistry. RESULTS: COMP mRNA and protein were detected at moderate to high levels in chronic pancreatitis tissues, at moderate levels in pancreatic cancer tissues, but at low levels in normal pancreatic tissues and in four pancreatic cancer cell lines. COMP mRNA signals and immunoreactivity were strongly present in the cytoplasm of degenerating acinar cells in CP tissues as well as in CP-like lesions in pancreatic cancer tissues. COMP protein was also present in the fibrotic tissue in CP. In contrast, COMP expression was weak to absent in the cytoplasm of cancer cells in pancreatic cancer tissues, and in ductal cells and islet cells in normal pancreatic tissues. CONCLUSION: COMP is preferentially expressed in degenerating acinar cells in CP and in CP-like areas in pancreatic cancer, suggesting a potential role of this gene in the course of acinar cell degeneration and dedifferentiation. COMP might thus serve as a marker for tissue destruction and disease activity in CP.

Adolescent↗

PubMed2003

Preferential expression of cystein-rich secretory protein-3 (CRISP-3) in chronic pancreatitis.

BACKGROUND: Chronic pancreatitis (CP) is a progressive inflammatory process resulting in exocrine and endocrine pancreatic insufficiency in advanced stages. Cysteine-rich secretory protein (CRISP-3) has been identified as a defense-associated molecule with predominant expression in the salivary gland, pancreas and prostate. AIMS: In this study, we investigated CRISP-3 expression in normal pancreatic tissues, chronic pancreatitis tissues, pancreatic cancer tissues and pancreatic cancer cell lines, as well as in other gastrointestinal organs. MATERIALS AND METHODS: 15 normal pancreatic tissues, 14 chronic pancreatitis tissues and 14 pancreatic cancer tissues as well as three pancreatic cancer cell lines were analyzed. Moreover, hepatocellular carcinoma and esophageal, stomach and colon cancers were also analyzed together with the corresponding normal controls. RESULTS: CRISP-3 was expressed at moderate to high levels in chronic pancreatitis tissues and at moderate levels in pancreatic cancer tissues but at low levels in normal pancreatic tissues, and was absent in three pancreatic cancer cell lines. CRISP-3 expression was below the level of detection in all cancerous gastrointestinal tissues and in all normal tissues except 2 of 16 colon tissue samples. CRISP-3 mRNA signals and immunoreactivity were strongly present in the cytoplasm of degenerating acinar cells and in small proliferating ductal cells in CP tissues and CP-like lesions in pancreatic cancer tissues. In contrast, CRISP-3 expression was weak to absent in the cytoplasm of cancer cells as well as in acinar cells and ductal cells in pancreatic cancer tissues and normal pancreatic tissues. CONCLUSION: These results reveal that the distribution of CRISP-3 in gastrointestinal tissues is predominantly in the pancreas. High levels of CRISP-3 in acinar cells dedifferentiating into small proliferating ductal cells in CP and CP-like lesions in pancreatic cancer suggests a role of this molecule in the pathophysiology of CP.

Adolescent↗

PubMed2002

Immunohistochemical presentation in non-malignant and malignant Barrett's epithelium.

Barrett's esophagus, which is histologically characterized by metaplastic columnar epithelium, is a common condition observed in approximately 10-20% of patients with gastroesophageal reflux disease. These lesions can typically progress from metaplasia with atypia to low-grade dysplasia, high-grade dysplasia, and adenocarcinoma. It is of great clinical importance to correctly grade these lesions and to identify changes with a high risk of malignant transformation, inasmuch as high-grade dysplasias and early adenocarcinomas in patients with Barrett's esophagus have a high chance for cure. The identification of high-risk lesions in Barrett's esophagus by histologic evaluation has drawbacks, especially regarding sampling errors and frequent intra- and interobserver discrepancies in the histopathologic grading/staging of these lesions. Immunostaining with a variety of antibodies provides a better understanding of the process of malignant transformation and helps to identify early markers of malignant transformation in Barrett's esophagus lesions. In this review, we will summarize the current knowledge about the value of immunostaining in the diagnosis of malignant and non-malignant Barrett's epithelium and its role to better define lesions with high risk for malignancy in this disorder.

Barrett Esophagus↗

PubMed2001

HIV in the brain: RNA levels and patterns of zidovudine resistance.

OBJECTIVE: To examine the association between HIV RNA levels, patterns of antiretroviral resistance, and neurologic status. METHODS: Autopsy samples from 13 HIV-infected subjects were examined for HIV-1 viral RNA (vRNA), and viral reverse transcriptase (RT) genotype was determined. All subjects had been clinically characterized using standard instruments before death. RESULTS: The median HIV-1 vRNA level in brain samples from subjects with moderate dementia was 7.79 log(10) copies/g (range 5.56 to 9.75 log(10) copies/g) compared with 5.44 log(10) copies/g (range 3.51 to 9.32 log(10) copies/g) for mildly demented subjects and 4.87 log(10) copies/g (3.51 to 6.86 log(10) copies/g) for those obtained from nondemented individuals. There were differences between subjects with moderate dementia and nondemented subjects (p = 0.0002) and between subjects with moderate and mild dementia (p = 0.0128). No significant differences among the groups were observed for vRNA levels in peripheral tissues. Some demented subjects had relatively low levels of HIV-1 vRNA, and paradoxically some nondemented subjects had high vRNA brain levels. Little subject effect in vRNA was noted in peripheral regions, but high regional variation in vRNA was noted within the brain. Patterns of the major zidovudine (ZDV) RT mutations in brain and peripheral tissues were concordant in most subjects. Subjects with longer duration of exposure to ZDV tended to have lower brain vRNA levels and a greater number of RT mutations than those with limited to no exposure. CONCLUSIONS: The presence and severity of HIV dementia correlates with the levels of productive HIV replication within the brain. Other pathophysiologic events (including macrophage activation) probably also contribute to neurologic dysfunction.

AIDS Dementia Complex↗

PubMed2001

Impact of HIV type 1 drug resistance mutations and phenotypic resistance profile on virologic response to salvage therapy.

This study examines the association between presence of drug resistance mutations and phenotypic resistance at baseline to virologic response to salvage therapy in a community setting. The study population consisted of 58 antiretroviral drug-experienced patients with HIV-1 infection who had recently switched therapy because of virologic failure. Drug resistance mutations in the reverse transcriptase- and protease-coding regions and phenotypic susceptibility to 13 antiretroviral drugs were assessed at baseline. Plasma HIV-1 RNA levels were assessed at baseline and at subsequent clinic visits. Results showed that three variables were significant in predicting virologic response: HIV-1 levels at baseline, number of protease mutations, and phenotypic sensitivity score for the regimen at baseline. For four drugs there was a significant association between the presence of specific drug resistance mutations and >10-fold phenotypic resistance to that drug. With phenotypic resistance defined as >4-fold resistance, the association between specific drug resistance mutations and phenotypic resistance was significant for seven drugs. Overall, these data show that phenotypic susceptibility and absence of drug resistance mutations, particularly protease mutations, are significant predictors of virologic response. For several drugs, specific combinations of drug resistance mutations are associated with decreased phenotypic susceptibility and might provide useful clinical guidelines in selecting therapeutic options.

Adult↗

PubMed2001

The anti-apoptotic protein BAG-3 is overexpressed in pancreatic cancer and induced by heat stress in pancreatic cancer cell lines.

Pancreatic cancer cells are usually resistant to apoptosis mediated by intrinsic or extrinsic factors. BAG-3 (Bis, CAIR), which was identified as a BAG-1-related protein, is a novel modulator of cellular anti-apoptotic activity that functions through its interaction with Bcl-2. In this study we analyzed BAG-3 expression in human pancreatic cancer tissues and cell lines. BAG-3 mRNA was expressed at moderate to high levels in all pancreatic cancer samples, but at low levels in normal pancreas tissues. In situ hybridization and immunohistochemistry analysis revealed that BAG-3 was present in the cancer cells within the pancreatic tumor mass. When BAG-3 mRNA was analyzed in other gastrointestinal cancers (hepatocellular carcinoma; esophageal, stomach and colon cancer), no difference was found from their corresponding normal controls. In pancreatic cancer cells, BAG-3 mRNA expression levels were strongly induced after heat stress, but not in response to members of the tumor necrosis factor (TNF)-alpha family (TNF-alpha, TRAIL, FasL). These findings indicate that in pancreatic cancer, in contrast to other gastrointestinal malignancies, increased levels of BAG-3 might function to block apoptosis. This characteristic of pancreatic cancer might contribute to its more aggressive growth behavior and poor responsiveness to treatment in vivo.

Adaptor Proteins, Signal Transducing↗

PubMed2001

Thymidine analog and multinucleoside resistance mutations are associated with decreased phenotypic susceptibility to stavudine in HIV type 1 isolated from zidovudine-naive patients experiencing viremia on stavudine-containing regimens.

Studies have demonstrated that HIV-1 isolated from subjects experiencing virologic failure on stavudine (d4T)-containing regimens often contains thymidine analog mutations (TAMs), consisting of reverse transcriptase (RT) mutations M41L, D67N, K70R, L210W, T215Y/F, and K219Q/E, previously associated only with zidovudine (ZDV) resistance. In clinical study NZT40012, HIV-1 was isolated from 86 ZDV-naive subjects experiencing viremia on d4T-based therapies (plasma HIV-1 RNA > or =1000 copies/ml) and analyzed to examine the association between RT mutations and phenotypic resistance to d4T. Resistance-associated mutations were analyzed from HIV-1 isolated from 85 subjects. Of these, 24 samples (28%) had TAMs, and 30 samples (35%) had either TAMs and/or the Q151M multinucleoside resistance (MNR) mutation. Phenotypic susceptibility to d4T was determined by two commercially available methods. Statistically significant increases (p < 0.001) in phenotypic fold resistance to d4T were observed in virus with at least one TAM or MNR mutation. However, the mean increases in phenotypic resistance were 4-fold for the Antivirogram assay and 3-fold for the Phenosense HIV assay, only slightly above the levels used to designate decreased susceptibility to d4T. Subjects can experience viremia on d4T-containing regimens with virus exhibiting only small increases in IC(50), suggesting that relatively small changes in viral susceptibility to d4T may influence drug efficacy.

Anti-HIV Agents↗

PubMed2001

Heparanase expression in primary and metastatic pancreatic cancer.

The human endoglycosidase heparanase (hpa) degrades heparan-sulfate proteoglycans, which constitute prominent components of basement membranes and extracellular matrix. Due to the critical function of hpa in cancer cell invasion and metastasis, we have analyzed the expression of hpa in human primary and metastatic pancreatic cancer as well as in the normal pancreas and in chronic pancreatic inflammation. By real-time quantitative PCR, there was a 7.9- and 30.2-fold increase of hpa mRNA in chronic pancreatitis and pancreatic cancer tissue samples, respectively, in comparison with normal pancreatic tissues. There was a significant correlation between enhanced hpa mRNA expression and shorter postoperative patient survival. hpa mRNA and protein localized in the cancer cells of primary and metastatic pancreatic cancer, with a preferentially higher expression at the primary tumor site. Cultured pancreatic cancer cells transfected with a full-length hpa construct displayed enhanced invasiveness in an invasion chamber assay. These results suggest that hpa overexpression in human pancreatic cancers facilitates cancer cell invasion, thereby enhancing the metastatic potential of the tumors.

Adult↗

PubMed2001

[Effects of aspirin on ferritin expression and resistance to oxidative damage in endothelial cells].

OBJECTIVE: To explore the mechanism of Aspirin induced ferritin synthesis on resistance to oxidative damage in endothelial cells. METHODS: Using cultured endothelial cells, we measured the effect of aspirin with different incubative time (4 - 24 h) and different concentration (0.1 - 3 mmol/L), salicylic acid and indomethacin induced ferritin expression by ELISA kit, and observed the change of lactate dehydrogenase (LDH) release rate, malondialdehyde (MDA) and cellular viability after preincubating the cell for 8 h with aspirin on resistance to hydrogen peroxide toxicity. Statistical analysis using a one-way analysis of variance. RESULTS: Aspirin at low concentration (0.1 mmol/L) induced significant increase ferritin expression in a concentration-dependent fashion: (5.8 +/- 0.3) ng/10(6) cell (0.1 mmol/L As), (6.4 +/- 0.4) ng/10(6) cell (0.5 mmol/L As), (7.0 +/- 0.7) ng/10(6) cell (1 mmol/L As), (7.4 +/- 0.4) ng/10(6) cell (2 mmol/L As), (7.7 +/- 0.5) ng/10(6) cell (3 mmol/L As), significant for all values: P < 0.05 versus normal control. Induction of ferritin levels by aspirin (1 mmol/L) was also time dependent: (5.8 +/- 1.0) ng/10(6) cell (4 h, but P > 0.05 vs control), (6.5 +/- 1.0) ng/10(6) cell (8 h, P < 0.05 vs control) and (7.8 +/- 0.8) ng/10(6) cell (24 h). Preincubating the cells with aspirin (0.1 mmol/L) reduced LDH release rate by 50%, toxicity reduction by 40%, and significant decrease MDA production. Aspirin induced cytoprotection from H(2)O(2) damage was also in a concentration dependent fashion. The cytoprotection of aspirin was mimicked by exogenous iron-free apo-ferritin but not iron-load ferritin. Salicylic acid and indomethacin failed to increase ferritin expression. CONCLUSION: Aspirin could induce significant increase ferritin synthesis at low concentration (0.1 mmol/L). Ferritin induction by aspirin was specific in nonsteroidal anti-inflammatory drugs.

Antioxidants↗

PubMed2001

Transplantation of lungs from a non-heart-beating donor.

BACKGROUND: In animals, we have previously done successful lung transplantations using organs from non-heart-beating donors. We have also developed an ex-vivo system of assessing the function of such organs before transplantation. The next stage was to try the technique in human beings. Bearing in mind the sensitive ethical issues involved, our first aim was to find out what procedures would be acceptable, and to use the results to guide a clinical lung transplantation from a non-heart-beating donor. METHODS: The ethical acceptability of the study was gauged from the results of a broad information programme directed at the general public in Sweden, and from discussions with professionals including doctors, nurses, hospital chaplains, and judges. The donor was a patient dying of acute myocardial infarction in a cardiac intensive-care unit after failed cardiopulmonary resuscitation. The next of kin gave permission to cool the lungs within the intact body, and intrapleural cooling was started 65 min after death. Blood samples were sent for virological testing and cross matching. The next of kin then had time to be alone with the deceased. After 3 h, the body was transported to the operating theatre and the heart-lung block removed. The lungs were assessed ex vivo, and the body was transported to the pathology department for necropsy. RESULTS: No contraindications to transplantation were found, and the right lung was transplanted successfully into a 54-year-old woman with chronic obstructive pulmonary disease. The donor lung showed excellent function only 5 min after reperfusion and ventilation, and during the first 5 months of follow-up, the function of the transplanted lung has been good. INTERPRETATION: About half the deaths in Sweden are caused by cardiac and cerebrovascular disease. This group could be a potential source of lung donors. When all hospitals and ambulance personnel in Sweden have received training in non-heart-beating lung donation, we hope that there will be enough donor lungs of good quality for all patients needing a lung transplant.

Cadaver↗

PubMed2001

Twice-daily triple nucleoside intensification treatment with lamivudine-zidovudine plus abacavir sustains suppression of human immunodeficiency virus type 1: results of the TARGET Study.

This open-label, multicenter, single-arm clinical trial assessed the 48-week efficacy of a twice-daily triple nucleoside reverse-transcriptase inhibitor regimen containing a lamivudine (150 mg)-zidovudine (300 mg) combination tablet (COM) and abacavir (ABC; 300 mg) in 87 antiretroviral therapy-experienced, protease inhibitor-naive patients infected with human immunodeficiency virus type 1 (HIV-1). At baseline, the median plasma HIV-1 RNA level was 3.10 log(10) copies/mL, and the median CD4 cell count was 506 cells/mm(3). An intent-to-treat&rcolon;observed analysis showed that, at weeks 24 and 48 of treatment, HIV-1 RNA level was <400 copies/mL in 48 (76%) of 63 and 45 (82%) of 55 patients, respectively, and <50 copies/mL in 37 (59%) of 63 and 31 (56%) of 55 patients, respectively. Previous zidovudine or lamivudine use and presence at baseline of the M184V reverse-transcriptase mutation did not impact virologic response. Median CD4 cell counts were maintained above baseline throughout the study. COM plus ABC was generally well tolerated.

Adult↗

PubMed2001

Surveillance of pre-malignant disease of the pancreatico-biliary system.

Technical advancements in ultrasonography, contrast-enhanced computed tomography and magnetic resonance imaging, as well as the wider availability of these ultramodern imaging techniques, have resulted in the early detection and a better classification of various asymptomatic and symptomatic pancreatico-biliary lesions. Pre-malignant biliary and pancreatic lesions are rare disorders, and no clear data are available to define their malignant potential. Because of the lack of controlled epidemiological data, the time span for malignant transformation and its frequency cannot be defined in the majority of these lesions. Adenomyomatosis of the gallbladder and gallbladder polyps larger than 10 mm should be treated by cholecystectomy even in asymptomatic patients because of an increased risk of malignant transformation. Chronic cholangitis, primary sclerosing cholangitis and choledochal cysts are also pre-malignant conditions. The timing of surgery, once it is advised for a pre-malignant condition that is still benign, should, however, be individualized to the particular patient situation. In patients with chronic pancreatitis, surgery may be indicated for disease-related complications. In as much as chronic pancreatitis predisposes to a higher risk of pancreatic cancer, any suspicion of malignancy should warrant a surgical exploration. Intraductal papillary tumours and mucin-producing pancreatic tumours are other pre-malignant pancreatic lesions whose malignant potential cannot be precisely determined pre-operatively. They should be resected in situations where there is a high degree of suspicion even without a clear objective diagnosis. In conclusion, pre-malignant hepato-biliary and pancreatic lesions of uncertain pathology should undergo early resection in view of treatment limitations and the dismal prognosis of established cancers. While hepato-biliary and pancreatic surgery is nowadays performed in specialized centres, with a low post-operative morbidity and mortality, it is equally important to understand that observation alone with regular computed tomography or magnetic resonance imaging control can no longer be recommended in the management of these lesions.

Biliary Tract Neoplasms↗

PubMed2001

Identification of disease-specific genes in chronic pancreatitis using DNA array technology.

OBJECTIVE: To use DNA arrays to analyze the differential gene expression patterns in the normal pancreas and in pancreatic diseases. SUMMARY BACKGROUND DATA: Genome-wide gene expression analysis will provide new insights into gene function and cause of disease. METHODS: RNA was extracted from eight normal pancreatic specimens, eight specimens with chronic pancreatitis (CP), and eight pancreatic cancer (PCa) tissues. Poly A(+) RNA was purified, reverse-transcribed, and converted into cRNA using biotinylated nucleotides. The HuGeneFL DNA array containing 5,600 full-length human genes was used for analysis. RESULTS: First, normal pancreatic tissues were analyzed in comparison with a panel of other normal tissues (colon, liver, prostate, lung, lymph node). This analysis revealed 11 signature genes that were selectively expressed in the pancreas (e.g., pancreatic elastase-IIA). Comparison of the expression of 5,600 genes between the normal pancreas, CP, and PCa specimens showed that the expression of 34 genes was decreased in CP tissues compared with normal pancreatic tissues, and that the expression of all of these genes was simultaneously decreased in PCa. In addition, the expression of 157 genes was increased in CP tissues compared with the normal pancreas. Of those, 152 genes were simultaneously increased in PCa. Thus, only 5 of 5,600 genes were significantly overexpressed in CP compared with both normal pancreas and PCa. CONCLUSIONS: The majority of alterations observed in CP are present in PCa, and the number of genes whose expression is selectively deregulated in CP is surprisingly small. These results may provide new insight into the pathobiology of CP and help identify certain molecular alterations that might serve as targets for new diagnostic tools and disease-specific therapy.

Adult↗

PubMed2001

Suicide attempts in the "comprehensive community mental health services for children and their families" program.

OBJECTIVE: To compare clinical characteristics of youths who had attempted suicide recently, previously but not recently, repeatedly, or never. METHOD: The sample comprised 4,677 youths receiving services between 1993 to 1998 in 22 communities and participating in the national evaluation of the Comprehensive Community Mental Health Services for Children and Their Families Program. Data on suicide attempts, demographics, and clinical characteristics were obtained from intake interviews and referring agencies. Chi-square and univariate analyses of variance were used for between-group comparisons. RESULTS: Twenty-one percent of the sample had a history of attempted suicide. Previous and repeat attempters were more likely to have a history of family violence and substance abuse. Repeat attempters were most likely to have depression, while never and previous (but not recent) attempters were more likely to have conduct disorder. Other clinical differences were also found. CONCLUSIONS: Among children receiving mental health services, those who attempt suicide experience more and different types of distress, depending on the recency and frequency of attempts. Clinicians should be aware that depression is not a necessary factor in predicting suicide attempts and that suicide risk is also associated with violent and aggressive behaviors.

Activities of Daily Living↗