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1.
Article in English | MEDLINE | ID: mdl-39259187

ABSTRACT

BACKGROUND: Bridging from temporary microaxial left ventricular assist device (tLVAD) to durable left ventricular assist device (dLVAD) is playing an increasing role in the treatment of terminally ill heart failure patients. Scant data exits about the best implantation strategy. The aim of this study is to analyze differences in dLVAD implantation technique and effects on patient outcomes. METHODS: Data from 341 patients (19 European centers), between 01/2017 and 10/2022, who underwent bridge to bridge implantation from tLVAD to dLVAD were retrospectively analyzed. The outcomes of the different implantation techniques on cardiopulmonary bypass (CPB), extracorporeal life support (ECLS) or tLVAD were compared. RESULTS: Durable LVAD implantation was performed employing CPB in 70% of cases (n = 238, group 1), ECLS in 11% (n = 38, group 2) and tLVAD in 19% (n = 65, group 3).Baseline characteristics showed no significant differences in age (p = 0.140), BMI (p = 0.388), creatinine (p = 0.659), Meld score (p = 0.190) and rate of dialysis (p = 0.110). Group 3 had significantly less patients with preoperatively invasive ventilation and cardiopulmonary resuscitation before tLVAD implantation (p = 0.009 and p < 0.001 respectively). Concomitant procedures were performed more often in group 1 and 2 compared to group 3 (24%, 37% and 5%, respectively, p < 0.001).The 30-day mortality showed a significant better survival after inverse probability of treatment weighting in group 3, but the 1-year mortality showed no significant differences between groups (p = 0.012 and 0.581, respectively).Post-operative complications like rate of RVAD implantation or re-thoracotomy due to bleeding, post-operative respiratory failure and renal replacement therapy showed no significant differences between groups.Freedom from first adverse event like stroke, driveline infection or pump thrombosis during follow-up was not significantly different between groups.Post-operative blood transfusion within 24-hours were significantly higher in groups 1 and 2 compared to surgery on tLVAD support (p < 0.001 and p = 0.003, respectively). CONCLUSIONS: In our analysis, the transition from tLVAD to dLVAD without further circulatory support did not show a difference in post-operative long-term survival, but a better 30-day survival was reported. The implantation by using only tLVAD showed a reduction in post-operative transfusion rates, right heart failure and the re-thoracotomy rate without increasing the risk of postoperative stroke or pump thrombosis. In this small cohort study, our data supports the hypothesis that we could demonstrate dLVAD implantation on tLVAD is a safe and feasible technique in selected patients.

2.
Theor Popul Biol ; 82(3): 187-99, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22750164

ABSTRACT

Phenotypic variability in a microorganism population is thought to be advantageous in fluctuating environments, however much remains unknown about the precise conditions for this advantage to hold. In particular competition for a growth-limiting resource and the dynamics of that resource in the environment modify the tradeoff between different effects of variability. Here we investigate theoretically a model system for variable populations under competition for a flowing resource that governs growth (chemostat model) and changes with time. This environment generally induces density-dependent selection among competing sub-populations. We characterize quantitatively the transient dynamics in this system, and find that equilibration between total population density and environment can occur separately and with a distinct timescale from equilibration between competing sub-populations. We analyze quantitatively the two opposing effects of heterogeneity--transient response to change, and fitness at equilibrium--and find the optimal strategy in a fluctuating environment. We characterize the phase diagram of the system in term of its optimal strategy and find it to be strongly dependent on the typical timescale of the environment and weakly dependent on the internal parameters of the population.


Subject(s)
Microbiology , Phenotype
3.
Lung Cancer ; 77(3): 605-10, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22704426

ABSTRACT

Induction cisplatin-based CT improves survival in resectable non-small cell lung cancer (NSCLC). We aimed to determine the respective activity of third-generation (gemcitabine-vinorelbine-cisplatin [GVP]) in comparison with second-generation drugs CT (mitomycine-ifosfamide-cisplatin [MIP]) and their cost-effectiveness as neoadjuvant CT before surgery in NSCLC. Patients with histologically proven initially untreated resectable stages I-III NSCLC were randomised between three courses of MIP or GVP followed by surgery. A two-stage Simon design was used for each arm with resectability rate as primary endpoint. A cost minimisation analysis, considering the direct medical costs, was performed in the Belgian and French social security systems. From 2001 to 2007, 140 patients (pts) were randomised (MIP 69, GVP 71). Main characteristics were: stage I/II/III in 52, 37 and 51 pts, squamous histology in 82 pts, male 114 pts, median PS 90. Objective response rates to induction CT were 60% (MIP) and 65% (GVP) (p=0.55). Complete resection rates were 77% (MIP) and 80% (GVP) (p=0.62). Median survival times were 47.2 months (MIP) and 36.6 months (GVP) (p=0.41). Cost-analyses showed significant incremental costs with GVP. In conclusion, while both neoadjuvant chemotherapy regimens shared similar efficacy in patients with resectable NSCLC, costs were significantly higher for third-generation regimens.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/therapy , Lung Neoplasms/therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/economics , Carcinoma, Non-Small-Cell Lung/economics , Carcinoma, Non-Small-Cell Lung/mortality , Cisplatin/administration & dosage , Costs and Cost Analysis , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Female , Humans , Ifosfamide/administration & dosage , Kaplan-Meier Estimate , Lung Neoplasms/economics , Lung Neoplasms/mortality , Male , Middle Aged , Mitomycin/administration & dosage , Multivariate Analysis , Neoadjuvant Therapy/economics , Proportional Hazards Models , Treatment Outcome , Vinblastine/administration & dosage , Vinblastine/analogs & derivatives , Vinorelbine , Gemcitabine
4.
Child Adolesc Psychiatr Clin N Am ; 18(4): 979-1000, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19836700

ABSTRACT

Childhood insomnias (CI) are a diverse group of sleep-related problems that present across the first 2 decades of life, ranging widely in severity. Little is understood about the origins of CI which are likely heterogeneous. Nevertheless, effective treatments for younger children have been shown to be efficacious. Defined within a development framework, this article reviews common correlates and causes of CI during the first two decades. A practical approach to the evaluation and treatment of insomnias among children and youth is presented.


Subject(s)
Sleep Initiation and Maintenance Disorders/diagnosis , Adolescent , Behavior Therapy , Child , Child, Preschool , Circadian Rhythm , Cognitive Behavioral Therapy , Cross-Sectional Studies , Diagnosis, Differential , Extinction, Psychological , Humans , Infant , Polysomnography , Risk Factors , Sleep Deprivation/psychology , Sleep Initiation and Maintenance Disorders/epidemiology , Sleep Initiation and Maintenance Disorders/etiology , Sleep Initiation and Maintenance Disorders/therapy , Social Environment
5.
Liver Transpl ; 7(12): 1081-4, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11753911

ABSTRACT

Hepatopulmonary syndrome (HPS) is an infrequent complication of liver cirrhosis. Orthotopic liver transplantation (OLT) has gained increasing acceptance as a treatment modality for HPS, although there have been reports of HPS developing after OLT with documented recurrence of cirrhosis. We describe the case of a 9-year-old boy who underwent OLT at 7 months of age because of biliary atresia. He subsequently developed HPS in the setting of chronic rejection without cirrhosis or evidence of portal hypertension. Re-OLT resulted in resolution of HPS and a good clinical outcome.


Subject(s)
Hepatopulmonary Syndrome/etiology , Liver Transplantation/adverse effects , Child , Graft Rejection/complications , Hepatopulmonary Syndrome/physiopathology , Hepatopulmonary Syndrome/surgery , Humans , Liver/pathology , Male , Reoperation , Time Factors
6.
Gastrointest Endosc ; 54(6): 714-9, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11726846

ABSTRACT

BACKGROUND: The aims of this study were to determine the utility of EUS and EUS-guided fine needle aspiration (EUS-FNA) in the detection and confirmation of celiac lymph node metastasis in patients with esophageal cancer and to define EUS features predictive of celiac lymph node metastasis in these patients. METHODS: The records of 211 patients with esophageal cancer who underwent EUS staging were reviewed. The operating characteristics of EUS were determined in patients where either surgery, EUS-FNA of a celiac lymph node, or both were performed (n = 102). The association between selected variables and the presence of celiac lymph node metastasis was evaluated by univariate and multivariable analyses. RESULTS: EUS in 48 patients provided a true-positive diagnosis of celiac lymph node involvement, a false-positive and false-negative result, respectively, in 6 and 14 patients, and a true-negative diagnosis in 34 patients. The sensitivity of EUS in detecting celiac lymph node was 77% (95% CI [67, 88]), specificity 85% (95% CI [74, 96]), negative predictive value 71% (95% CI [58, 84]), and the positive predictive value 89% (95% CI [81, 97]). EUS-FNA was performed in 94% (51/54) of patients with celiac lymph nodes. The accuracy of EUS-FNA in detecting malignant celiac lymph nodes was 98% (95% CI [90, 100]). Advanced T-stage, the need for dilation, detection of peritumoral lymph nodes, and black race were associated with celiac lymph node involvement. In multivariable analysis, advanced T-stage was the strongest predictor of celiac lymph node involvement. CONCLUSION: EUS and EUS-FNA are highly accurate in detecting and confirming celiac lymph nodes metastasis. Depth of tumor invasion as assessed by EUS is a strong predictor of celiac lymph node metastasis in patients with esophageal cancer.


Subject(s)
Adenocarcinoma/diagnostic imaging , Adenocarcinoma/pathology , Endosonography/statistics & numerical data , Esophageal Neoplasms/diagnostic imaging , Esophageal Neoplasms/pathology , Esophagoscopy/methods , Lymph Nodes/pathology , Adenocarcinoma/secondary , Adult , Aged , Aged, 80 and over , Biopsy, Needle/statistics & numerical data , Celiac Artery/diagnostic imaging , Celiac Artery/pathology , Esophageal Neoplasms/surgery , False Negative Reactions , False Positive Reactions , Female , Humans , Logistic Models , Lymphatic Metastasis/diagnostic imaging , Male , Middle Aged , Neoplasm Staging , Predictive Value of Tests , Retrospective Studies , Sensitivity and Specificity , Statistics, Nonparametric
7.
Biochem J ; 360(Pt 1): 135-42, 2001 11 15.
Article in English | MEDLINE | ID: mdl-11696000

ABSTRACT

We hypothesized that certain proteins encoded by temperature-responsive genes in brown adipose tissue (BAT) contribute to the remarkable metabolic shifts observed in this tissue, thus prompting a differential mRNA expression analysis to identify candidates involved in this process in mouse BAT. An mRNA species corresponding to a novel partial-length gene was found to be induced 2-3-fold above the control following cold exposure (4 degrees C), and repressed approximately 70% by warm acclimation (33 degrees C, 3 weeks) compared with controls (22 degrees C). The gene displayed robust BAT expression (i.e. approximately 7-100-fold higher than other tissues in controls). The full-length murine gene encodes a 594 amino acid ( approximately 67 kDa) open reading frame with significant homology to the human hypothetical acyl-CoA thioesterase KIAA0707. Based on cold-inducibility of the gene and the presence of two acyl-CoA thioesterase domains, we termed the protein brown-fat-inducible thioesterase (BFIT). Subsequent analyses and cloning efforts revealed the presence of a novel splice variant in humans (termed hBFIT2), encoding the orthologue to the murine BAT gene. BFIT was mapped to syntenic regions of chromosomes 1 (human) and 4 (mouse) associated with body fatness and diet-induced obesity, potentially linking a deficit of BFIT activity with exacerbation of these traits. Consistent with this notion, BFIT mRNA was significantly higher ( approximately 1.6-2-fold) in the BAT of obesity-resistant compared with obesity-prone mice fed a high-fat diet, and was 2.5-fold higher in controls compared with ob/ob mice. Its strong, cold-inducible BAT expression in mice suggests that BFIT supports the transition of this tissue towards increased metabolic activity, probably through alteration of intracellular fatty acyl-CoA concentration.


Subject(s)
Adipose Tissue/enzymology , Obesity/genetics , Palmitoyl-CoA Hydrolase/biosynthesis , Palmitoyl-CoA Hydrolase/chemistry , Palmitoyl-CoA Hydrolase/genetics , Alternative Splicing , Amino Acid Sequence , Amino Acids/chemistry , Animals , Cloning, Molecular , Cold Temperature , DNA, Complementary/metabolism , Humans , Mice , Models, Genetic , Molecular Sequence Data , Open Reading Frames , Protein Structure, Tertiary , RNA, Messenger/metabolism , Radiation Hybrid Mapping , Reverse Transcriptase Polymerase Chain Reaction , Sequence Homology, Amino Acid , Temperature , Tissue Distribution
8.
Gastrointest Endosc ; 54(4): 441-7, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11577304

ABSTRACT

BACKGROUND: EUS-guided fine needle aspiration (EUS-FNA) is a highly accurate method of detecting malignant lymphadenopathy. The optimal methods for performing EUS-FNA to maximize sensitivity and to minimize the number of needle passes necessary are unknown. This is a report of the results of a prospective randomized controlled trial to determine the effect of suction, the site of FNA (edge or center of lymph node), and the method of preparation of cytologic specimens on accuracy, number of needle passes needed, and specimen quality. METHODS: Consecutive patients with lymphadenopathy detected by EUS underwent FNA. Each lymph node was sampled with or without suction and from the edge or center in a 2 x 2 factorial design. The samples were expressed onto slides for cytology, and the residual material in the needle was analyzed by the cytospin-cellblock technique. Each aspirate was individually characterized for a diagnosis of malignancy, cellularity, and bloodiness. RESULTS: Forty-three patients with a total of 46 lymph nodes were evaluated. The final lymph node diagnosis was benign in 22 (48%), "suspicious for malignancy" in 6 (13%), and malignant in 18 (39%). The use of suction was associated with an increase in the cellularity of the specimen, but did not improve the likelihood of obtaining a correct diagnosis (OR 1.52: 95% CI [0.81, 2.85]). Samples obtained with suction were of worse quality because of excessive bloodiness (OR 4.7: 95% CI [1.99, 11.24]). Aspiration from the edge of the lymph node (compared with the center) did not increase the likelihood of a correct diagnosis (OR 1.16: 95% CI [0.42, 3.21]). For 78% of malignant lymph nodes, the correct diagnosis was obtained on the first needle pass and for 100% by the third pass. Cytospin-cellblock methods did not add any additional diagnostic information compared with direct smear cytology. CONCLUSIONS: The traditional method of applying suction during EUS-FNA does not improve diagnostic accuracy and worsens specimen bloodiness compared with FNA without suction. The site of FNA within the lymph node does not affect accuracy. When EUS-FNA is necessary, our recommendation is up to 3 FNAs without suction from the most convenient and safe location within abnormal-appearing lymph nodes.


Subject(s)
Biopsy, Needle/methods , Endosonography , Lymph Nodes/pathology , Lymphatic Diseases/diagnosis , Lymphatic Metastasis/pathology , Humans , Prospective Studies , Specimen Handling , Suction
10.
Hum Pathol ; 32(4): 368-78, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11331953

ABSTRACT

Morphologic assessment of dysplasia in Barrett esophagus, despite limitations, remains the basis of treatment. We rigorously tested modified 1988 criteria, assessing intraobserver and interobserver reproducibility. Participants submitted slides of Barrett mucosa negative (BE) and indefinite (IND) for dysplasia, with low-grade dysplasia (LGD) and high-grade dysplasia (HGD), and with carcinoma. Two hundred fifty slides were divided into 2 groups. The first 125 slides were reviewed, without knowledge of the prior diagnoses, on 2 occasions by 12 gastrointestinal pathologists without prior discussion of criteria. Results were analyzed by kappa statistics, which correct for agreement by chance. A consensus meeting was then held, establishing, by group review of the index 125 slides, the criteria outlined herein. The second 125-slide set was then reviewed twice by each of the same 12 pathologists, and follow-up kappa statistics were calculated. When statistical analysis was performed using 2 broad diagnostic categories (BE, IND, and LG v HG and carcinoma), intraobserver agreement was near perfect both before and after the consensus meeting (mean kappa = 0.82 and 0.80). Interobserver agreement was substantial (kappa = 0.66) and improved after the consensus meeting (kappa = 0.70; P =.02). When statistical analysis was performed using 4 clinically relevant separations (BE; IND and LGD; HGD; carcinoma), mean intraobserver kappa improved from 0.64 to 0.68 (both substantial) after the consensus meeting, and mean interobserver kappa improved from 0.43 to 0.46 (both moderate agreement). When statistical analysis was performed using 4 diagnostic categories that required distinction between LGD and IND (BE; IND; LGD; HGD and carcinoma), the pre-consensus meeting mean intraobserver kappa was 0.60 (substantial agreement), improving to 0.65 after the meeting (P <.05). Interobserver agreement was poorer, with premeeting and postmeeting mean values unchanged (kappa = 0.43 at both times). Interobserver agreement was substantial for HGD/carcinoma (kappa = 0.65), moderate to substantial for BE (kappa = 0.58), fair for LGD (kappa = 0.32), and slight for IND (kappa = 0.15). The intraobserver reproducibility for the diagnosis of dysplasia in BE was substantial. Interobserver reproducibility was substantial at the ends of the spectrum (BE and HG/carcinoma) but slight for IND. Both intraobserver and interobserver variation improved overall after the application of a modified grading system developed at a consensus conference but not in separation of BE, IND, and LGD. The criteria used by the group are presented. HUM PATHOL 32:368-978.


Subject(s)
Barrett Esophagus/diagnosis , Algorithms , Barrett Esophagus/pathology , Clinical Laboratory Techniques/standards , Humans , Tissue Fixation
11.
Hum Pathol ; 32(4): 379-88, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11331954

ABSTRACT

The objective of endoscopic surveillance in Barrett esophagus (BE) is to assess the risk of subsequent development of invasive carcinoma. Criteria for morphologic evaluation of dysplasia, the presumed precursor lesion, have been established, although there are surprisingly few data in the literature correlating biopsy diagnosis of dysplasia with outcome. We collected follow-up information on 138 patients with BE whose initial endoscopic biopsy specimens had been selected for submission in an interobserver variability study performed by 12 pathologists with special interest in gastrointestinal pathology and reviewed blindly twice each by all the participants. Cases were scored as BE with no dysplasia, atypia indefinite for dysplasia (IND), low-grade dysplasia (LGD), high-grade dysplasia (HGD), intramucosal carcinoma, and frankly invasive carcinoma, thus generating 24 scores on each biopsy specimen. Clinical follow-up was obtained and correlated with both the submitting diagnoses and majority diagnoses. Kaplan-Meier statistics were used to compare both the submitting and majority diagnoses with outcome using detection or documentation of invasive carcinoma as the endpoint. Using the submitting diagnoses, no invasive carcinomas were detected in 44 cases diagnosed as BE (median follow-up, 38.5 months). Carcinomas were detected in 4 of 22 (18%) cases submitted as IND (median progression-free survival of 62 months), in 4 of 25 (15%) cases of LGD (median progression-free survival of 60 months), in 20 of 33 cases of HGD (median progression-free survival, 8 months), and all 13 (100%) cases submitted as adenocarcinoma. Grade on initial biopsy correlated significantly with progression to invasive carcinoma (log-rank P =.0001). Majority diagnosis was achieved in 99 of the cases. Using the majority diagnoses, no invasive carcinomas were found in 50 cases of BE (median follow-up, 48 months), and carcinomas were detected in 1 of 7 (14%) IND cases (80% progression-free survival at 2 months), 3 of 15 (20%) LGD (median progression-free survival, 60 months), 9 of 15 (60%) HGD (median progression-free survival, 7 months), and all 12 (100%) carcinoma. Initial grading again correlated significantly with progression to invasive carcinoma (log-rank P =.0001). However, there were 39 cases without a majority diagnosis. Among these, no carcinomas developed in 8 cases with an average score between BE and IND. Carcinomas were detected in 9 of 21 (43%) cases with an average score between IND and LGD, and 7 of 10 (70%) cases with an average score between LGD and HGD. There were ulcers in 8 of 39 cases (20%) of the "no-majority" group and in 13 of 99 (13%) of the majority cases. Of 21 total ulcerated cases, cancer was demonstrated in 15 (71%) of these on follow-up. These data support combining the IND and LGD categories for surveillance purposes. Cases without dysplasia may be followed up conservatively. The data obtained from submitted diagnoses as opposed to those from blind review suggest that knowledge of the clinical findings aids in diagnosis. The data also support the assertion that HGD is strongly associated with invasive carcinoma. Rebiopsy of ulcerated areas should be considered because they may harbor malignancy. Histologic grading of dysplasia using established criteria is a powerful prognosticator in BE. HUM PATHOL 32:379-388.


Subject(s)
Barrett Esophagus/complications , Carcinoma/etiology , Esophageal Neoplasms/etiology , Esophagus/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Barrett Esophagus/pathology , Biomarkers, Tumor , Carcinoma/pathology , Child , Esophageal Neoplasms/pathology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Predictive Value of Tests
12.
J Immunol Methods ; 250(1-2): 67-79, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11251222

ABSTRACT

Since their development in the early 1990s, differential gene expression (DGE) technologies have been applied to a multitude of biological challenges, both for the purpose of basic biological research and as a valuable tool for the discovery and development of pharmaceuticals. In this review we survey a class of DGE technologies collectively referred to as 'open' architecture systems. These technologies are distinct from the 'closed' DGE technologies (quantitative PCR, chip technologies), in that no pre-existing biological or sequence information is necessary and they are applicable to any species. Examples of open systems include GeneCalling, SAGE, TOGA, READS, and their progenitor DGE technologies, differential display and cDNA representational difference analysis. We review these technologies and summarize a specific application using GeneCalling for novel gene discovery. Additionally, the significance of data management and experimental design in this new age of expression analysis is discussed.


Subject(s)
Gene Expression Profiling/methods , Animals , Cell Line , Chemokines/genetics , DNA, Complementary/genetics , Humans
13.
Biochem J ; 353(Pt 2): 369-75, 2001 01 15.
Article in English | MEDLINE | ID: mdl-11139402

ABSTRACT

Using differential mRNA expression analysis, a previously uncharacterized gene was found to be up-regulated 2-fold in brown adipose tissue (BAT) of mice exposed to cold (4 degrees C) for 48 h. Contig and homology analysis revealed that the gene represents the murine orthologue to a sequence from a public database encoding a putative human protein (CGI-69). The presence of mitochondrial carrier domains in the human protein, its transmembrane topology and cold-induction of the mouse CGI-69 gene in BAT prompted an analysis of the idea that CGI-69 may represent a new uncoupling protein (UCP) functional homologue. However, transfection of human CGI-69 isoforms in HEK-293 cells yielded no change in mitochondrial membrane potential (Deltapsi(m)), despite localization of FLAG-tagged CGI-69 to mitochondria of MCF7 cells. Surprisingly, overexpression of the human 2-oxoglutarate carrier (OGC) protein (originally designed as a negative control) sparked a significant drop in Deltapsi(m), possibly signalling a previously unappreciated uncoupling activity for the OGC.


Subject(s)
Adipose Tissue, Brown/metabolism , Carrier Proteins/biosynthesis , Intracellular Membranes/metabolism , Membrane Proteins/biosynthesis , Membrane Transport Proteins , Mitochondria/metabolism , Mitochondrial Proteins , Recombinant Fusion Proteins , Amino Acid Sequence , Animals , Carrier Proteins/genetics , Cell Line , Cold Temperature , Male , Membrane Potentials , Mitochondrial Membrane Transport Proteins , Molecular Sequence Data , Rats , Sequence Homology, Amino Acid
14.
Am J Pathol ; 156(6): 1887-900, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10854212

ABSTRACT

In the present study we have used a novel, comprehensive mRNA profiling technique (GeneCalling) for determining differential gene expression profiles of human endothelial cells undergoing differentiation into tubelike structures. One hundred fifteen cDNA fragments were identified and shown to represent 90 distinct genes. Although some of the genes identified have previously been implicated in angiogenesis, potential roles for many new genes, including OX-40, white protein homolog, KIAA0188, a homolog of angiopoietin-2, ADAMTS-4 (aggrecanase-1), and stanniocalcin were revealed. Support for the biological significance was confirmed by the abrogation of the changes in the expression of angiogenesis inhibitors and in situ hybridization studies. This study has significantly extends the molecular fingerprint of the changes in gene expression that occur during endothelial differentiation and provides new insights into the potential role of a number of new molecules in angiogenesis.


Subject(s)
Gene Expression , Neovascularization, Physiologic/genetics , Veins/physiology , Cells, Cultured , DNA Fingerprinting , DNA Fragmentation , DNA, Complementary/genetics , Endothelium, Vascular/physiology , Genome , Humans , In Situ Hybridization , Receptors, Cytoplasmic and Nuclear/physiology , Transcription Factors/physiology
15.
J Biol Chem ; 275(14): 10429-36, 2000 Apr 07.
Article in English | MEDLINE | ID: mdl-10744732

ABSTRACT

Absence of the hormone leptin leads to dramatic increases in appetite, food intake, and adiposity. The primary site of action, at least with respect to appetite, is the hypothalamus. Leptin also has significant effects on the function(s) of peripheral organs involved in maintaining body composition. Some of these effects are mediated through direct interaction of leptin with its receptor on the target tissue, and some effects are indirectly mediated through secondary hormonal and neural pathways. Few of the genes that are responsible for regulating body composition and the peripheral effects of leptin are known. We have used a new gene profiling technology to characterize gene expression changes that occur in the pituitary, hypothalamus, fat, muscle, and liver in response to both obesity and treatment with exogenous leptin. These differences were then overlaid to allow the identification of genes that are regulated by obesity and at least partially normalized by leptin treatment. By using this process we have identified five genes (POMC, PC2, prolactin, HSGP25L2G, and one novel) that are both abnormally expressed in the pituitaries of obese mice and are sensitive to the effects of leptin. We also show that adrenocorticotropic hormone appears to be involved in a regulatory loop involving leptin.


Subject(s)
Adrenocorticotropic Hormone/genetics , Gene Expression Regulation/physiology , Leptin/physiology , Obesity/genetics , Pituitary Gland/metabolism , Adipose Tissue/metabolism , Animals , Cells, Cultured , Female , Gene Expression Regulation/drug effects , Hypothalamus/metabolism , Leptin/pharmacology , Liver/metabolism , Mice , Mice, Inbred C57BL , Mice, Obese , Models, Biological , Muscle, Skeletal/metabolism , Obesity/physiopathology , Organ Specificity
16.
Immunity ; 12(2): 141-50, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10714680

ABSTRACT

Previously, we described AGM-derived endothelial cell lines that either inhibited or permitted the development of erythroid or B cells. We utilized a differential gene expression method to isolate a chemokine, termed WECHE, from one of these cell lines. WECHE inhibited the formation of erythroid cells but had no effect on either myeloid or B cell formation. WECHE repressed BFU-E development from either mouse fetal liver or bone marrow progenitor cells but had no effect on colony formation induced by IL-3 or IL-7. WECHE reduced HPP-CFC production from fetal liver-derived stem cells. WECHE hindered the growth of yolk sac-derived endothelial cells. WECHE was also chemotactic for bone marrow cells. Thus, WECHE is a novel chemokine that regulates hematopoietic differentiation.


Subject(s)
Chemokines/physiology , Hematopoiesis/physiology , Amino Acid Sequence , Animals , Cell Line , Chemokines/genetics , Chemokines, CXC , Chemotaxis/physiology , Female , Hematopoietic Stem Cells/cytology , Hematopoietic Stem Cells/physiology , Male , Mice , Mice, Inbred C57BL , Molecular Sequence Data , Sequence Homology, Amino Acid
17.
Pediatr Neurol ; 22(3): 182-6, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10734247

ABSTRACT

The long-term effects of monotherapy with levodopa or the dopamine agonist pergolide on the motor/sensory, behavioral, and cognitive variables in seven children with restless legs syndrome/periodic limb movements in sleep (RLS/PLMS) and attention-deficit-hyperactivity disorder (ADHD) were investigated. Five of the seven children had previously been treated with stimulants that had either been determined to be ineffective or to have intolerable side effects. Dopaminergic therapy improved the symptoms of RLS and reduced the number of PLMS per hour of sleep (P = 0.018) and associated arousals (P = 0.042) for the entire group. After treatment, three children no longer met the criteria for ADHD, and three reverted to normal on the Test of Variable Attention. ADHD improved in all seven as measured by the Connors parent rating scale (P<0.04) and the Child Behavior Checklist (P<0.05). A significant improvement also occurred in the visual, but not verbal, memory scores on the Wide Range Assessment of Memory and Learning (P<0.001). Five of seven children continue on dopaminergic therapy 3 years after treatment initiation, with good response. We postulate that the improvement in ADHD may be the result of the amelioration of RLS/PLMS and its associated sleep disturbance. Alternatively, ADHD and RLS/PLMS may share a common dopaminergic deficit.


Subject(s)
Attention Deficit Disorder with Hyperactivity/drug therapy , Dopamine Agonists/therapeutic use , Dopamine/metabolism , Nocturnal Myoclonus Syndrome/drug therapy , Pergolide/therapeutic use , Restless Legs Syndrome/drug therapy , Adolescent , Attention Deficit Disorder with Hyperactivity/complications , Attention Deficit Disorder with Hyperactivity/metabolism , Child , Humans , Male , Nocturnal Myoclonus Syndrome/complications , Nocturnal Myoclonus Syndrome/metabolism , Polysomnography , Remission Induction , Restless Legs Syndrome/complications , Restless Legs Syndrome/metabolism , Treatment Outcome
18.
J Dev Behav Pediatr ; 20(4): 244-52, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10475599

ABSTRACT

This article outlines several aspects of sleep regulation relevant to pediatric pain management. A broad range of connections between sleep and pain are described: (1) pain can interfere with the quality and quantity of children's sleep; (2) insufficient sleep (quality or quantity) can cause daytime sequelae (behavioral and emotional changes) that interfere with the coping skills necessary for effective pain management; (3) fear and anxiety often have a negative impact on both pain and sleep; (4) feelings of safety and control frequently have a positive effect on both sleep and pain symptoms; (5) adequate sleep seems to promote both physiological (tissue repair) and psychological (transient cessation of the perception of pain signals) processes relevant to recovery from pain, injury, and illness; and (6) treatment approaches to pediatric sleep and pain problems show considerable overlap with respect to many pharmacological as well as cognitive-behavioral interventions. Given these multiple links, a better understanding of sleep--and its importance in physical and mental health--is likely to be of value to clinicians and researchers working in areas of pediatric pain management. One specific hypothesis to be addressed is the possible contribution of sleep disruption as a step in the progression to some chronic pain syndromes.


Subject(s)
Pain/physiopathology , Sleep Wake Disorders/etiology , Sleep/physiology , Adaptation, Psychological , Brain/physiology , Brain/physiopathology , Child , Humans , Pain/complications , Pain/drug therapy , Pain/psychology , Perception/physiology
19.
Endoscopy ; 31(5): 377-82, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10433047

ABSTRACT

BACKGROUND AND STUDY AIMS: Sarcoidosis is a chronic multisystem granulomatous disease that is often diagnosed after a finding of hilar and mediastinal lymphadenopathy on a chest radiograph. This often requires further evaluation by transbronchial biopsy or other clinical parameters. The present study is a descriptive, retrospective one using endoscopic ultrasound with fine-needle aspiration (EUS-FNA) of mediastinal lymph nodes in seven patients with sarcoidosis. PATIENTS AND METHODS: Among 108 consecutive patients who underwent EUS-FNA of mediastinal lymph nodes for various clinical indications between July 1994 and October 1997, seven patients were found to have sarcoidosis on EUS-FNA, and the EUS morphology was studied in these patients. RESULTS: Sarcoidosis was diagnosed in seven patients using endosonographic characteristics and clinical follow-up. EUS with FNA showed cytological evidence of sarcoidosis in six patients. Seven patients were found to have subcarinal lymph nodes, and six patients had abnormally enlarged aortopulmonary (AP) window lymph nodes. The nodes in all patients had three endosonographic criteria for malignancy. The long axis of the largest mediastinal lymph nodes measured 3.44+/-1.42 cm (range 1.8-6.0 cm). The short axis measured 2.50+/-0.69 (range 1.0-4.0 cm). The average number of nodes seen in each patient was 2.80+/-0.75 (range 2-4). The nodes in all seven patients were discrete and well demarcated. A central hyperechoic strand was evident in these nodes in four patients (57%). There were no complications. CONCLUSIONS: Mediastinal lymph nodes in patients with sarcoidosis appear to have specific echo characteristics, and EUS-FNA can be used for confirmatory tissue diagnosis.


Subject(s)
Endosonography , Lymph Nodes/pathology , Mediastinal Diseases/diagnostic imaging , Sarcoidosis/diagnostic imaging , Adult , Aged , Biopsy, Needle , Bronchoscopy , Diagnosis, Differential , Feasibility Studies , Female , Follow-Up Studies , Humans , Lymph Nodes/diagnostic imaging , Male , Mediastinal Diseases/pathology , Middle Aged , Reproducibility of Results , Retrospective Studies , Sarcoidosis/pathology , Tomography, X-Ray Computed
20.
Arch Pathol Lab Med ; 123(8): 716-9, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10420230

ABSTRACT

Mucosa-associated lymphoid tissue (MALT) lymphomas are low-grade B-cell lymphomas that occur in a variety of extranodal sites but rarely as a primary hepatic lymphoma. We describe the histological findings, immunophenotype, and immunohistochemistry of one such lymphoma found incidentally in a 69-year-old woman. The lymphoid infiltrate invaded the liver in a serpiginous configuration with entrapment of nodules of normal liver. Reactive follicles were surrounded by intermediate-sized lymphoid cells with slightly irregular nuclei and pale cytoplasm. Only a few scattered lymphoepithelial lesions were identified since most of the bile ducts were destroyed. The immunophenotype determined by flow cytometry identified the lymphoid cells as being CD19, CD20 positive and exhibiting lambda light chain restriction. CD5, CD10, and CD23 were negative. Immunohistochemistry showed the neoplastic cells to be positive for CD20 (L-26) and bcl-2. The reactive follicles were negative for bcl-2. CD3 showed only a few scattered T cells. Cyclin D1 did not stain the neoplastic cells. Cytokeratin (AE1/AE3) highlighted the lymphoepithelial lesions and residual bile ducts. MALT lymphomas need to be recognized and distinguished from other B-cell lymphomas, particularly mantle cell lymphomas, because of the difference in behavior and treatment.


Subject(s)
Liver Neoplasms/diagnosis , Lymphoma, B-Cell, Marginal Zone/diagnosis , Aged , B-Lymphocytes/immunology , B-Lymphocytes/pathology , Cell Nucleus/pathology , Cytoplasm/pathology , Female , Flow Cytometry , Humans , Immunophenotyping , Liver Neoplasms/pathology , Lymphoma, B-Cell, Marginal Zone/pathology
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