A cigarette smoke-induced inflammatory process underlies the pathogenesis of the majority of pathologic lesions associated with chronic obstructive pulmonary disease (COPD). In chronic bronchitis, this process is located in the mucosa, gland ducts and glands of intermediate sized bronchi with an internal diameter of 2-4 mm. The mucus-containing exudate produced by the inflammatory response overpowers the normal clearance mechanisms, resulting in the cough and expectoration that characterize chronic bronchitis. In some cases of chronic bronchitis, the inflammatory process extends to smaller bronchi and bronchioles less than 2 mm in internal diameter. In this location, the inflammatory process thickens the wall, narrows the lumen and destroys the parenchymal support of the airways. These changes progressively increase peripheral airways resistance and eventually reduce the patient's ability to empty their lungs to a degree that can be measured by a reduction in FEV1 (forced expiratory volume in one second). The reduction in lung surface area produced by parenchymal inflammation contributes to the decline in FEV1 by reducing lung elastic recoil, which is the major force driving air out of the lung. It also contributes to the reduction in diffusing capacity by reducing the lung capillary bed. The purpose of this presentation is to review the quantitative aspects of these pathological changes and attempt to provide insight into factors which result in progression of these lesions.
{"title":"Chronic obstructive pulmonary disease: an overview of pathology and pathogenesis.","authors":"J. Hogg","doi":"10.1002/0470868678.CH2","DOIUrl":"https://doi.org/10.1002/0470868678.CH2","url":null,"abstract":"A cigarette smoke-induced inflammatory process underlies the pathogenesis of the majority of pathologic lesions associated with chronic obstructive pulmonary disease (COPD). In chronic bronchitis, this process is located in the mucosa, gland ducts and glands of intermediate sized bronchi with an internal diameter of 2-4 mm. The mucus-containing exudate produced by the inflammatory response overpowers the normal clearance mechanisms, resulting in the cough and expectoration that characterize chronic bronchitis. In some cases of chronic bronchitis, the inflammatory process extends to smaller bronchi and bronchioles less than 2 mm in internal diameter. In this location, the inflammatory process thickens the wall, narrows the lumen and destroys the parenchymal support of the airways. These changes progressively increase peripheral airways resistance and eventually reduce the patient's ability to empty their lungs to a degree that can be measured by a reduction in FEV1 (forced expiratory volume in one second). The reduction in lung surface area produced by parenchymal inflammation contributes to the decline in FEV1 by reducing lung elastic recoil, which is the major force driving air out of the lung. It also contributes to the reduction in diffusing capacity by reducing the lung capillary bed. The purpose of this presentation is to review the quantitative aspects of these pathological changes and attempt to provide insight into factors which result in progression of these lesions.","PeriodicalId":19323,"journal":{"name":"Novartis Foundation Symposium","volume":"18 10","pages":"4-19; discussion 19-26"},"PeriodicalIF":0.0,"publicationDate":"2008-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/0470868678.CH2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50780036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2008-10-07DOI: 10.1002/9780470030585.CH14
R. Frank
Actions that promote fairness are sometimes consistent with the pursuit of individual self-interest, sometimes not. The diner who leaves a generous tip at a favourite local restaurant, for example, may do so partly out of a sense of obligation to the waiter. But we need not invoke fairness to explain the tip, which is, after all, a prudent investment in obtaining good service in the future. In contrast, narrow self-interest cannot explain why travellers might leave tips in restaurants located along interstate highways. Because it is unlikely that they will ever visit these restaurants again, their failure to tip cannot affect the quality of service they expect to receive in the future. So it is hard to escape the conclusion that concerns about fairness must be implicated when diners tip on the road. Of course, merely to assert the existence of a sense of fairness does not really explain why people often set aside concern for narrow self-interest. It simply raises the more fundamental question of why people have a sense of fairness in the first place. It is this question I will discuss.
{"title":"Cooperation through moral commitment.","authors":"R. Frank","doi":"10.1002/9780470030585.CH14","DOIUrl":"https://doi.org/10.1002/9780470030585.CH14","url":null,"abstract":"Actions that promote fairness are sometimes consistent with the pursuit of individual self-interest, sometimes not. The diner who leaves a generous tip at a favourite local restaurant, for example, may do so partly out of a sense of obligation to the waiter. But we need not invoke fairness to explain the tip, which is, after all, a prudent investment in obtaining good service in the future. In contrast, narrow self-interest cannot explain why travellers might leave tips in restaurants located along interstate highways. Because it is unlikely that they will ever visit these restaurants again, their failure to tip cannot affect the quality of service they expect to receive in the future. So it is hard to escape the conclusion that concerns about fairness must be implicated when diners tip on the road. Of course, merely to assert the existence of a sense of fairness does not really explain why people often set aside concern for narrow self-interest. It simply raises the more fundamental question of why people have a sense of fairness in the first place. It is this question I will discuss.","PeriodicalId":19323,"journal":{"name":"Novartis Foundation Symposium","volume":"278 1","pages":"197-208; discussion 208-21"},"PeriodicalIF":0.0,"publicationDate":"2008-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"51133925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Food allergies affect approximately 2% of the population and are the single leading cause of anaphylaxis occurring outside of hospitals in westernized countries. Given the frequency of IgE-mediated food allergy, it is imperative that physicians appropriately diagnose food-allergic patients, educate them in the appropriate measures to prevent accidental ingestion of food allergens, teach them to recognize early signs of anaphylaxis, and arm them with medications and a treatment plan to utilize in case of the 'almost inevitable' accidental ingestion.
{"title":"Food-induced anaphylaxis.","authors":"H. Sampson","doi":"10.1002/0470861193.CH13","DOIUrl":"https://doi.org/10.1002/0470861193.CH13","url":null,"abstract":"Food allergies affect approximately 2% of the population and are the single leading cause of anaphylaxis occurring outside of hospitals in westernized countries. Given the frequency of IgE-mediated food allergy, it is imperative that physicians appropriately diagnose food-allergic patients, educate them in the appropriate measures to prevent accidental ingestion of food allergens, teach them to recognize early signs of anaphylaxis, and arm them with medications and a treatment plan to utilize in case of the 'almost inevitable' accidental ingestion.","PeriodicalId":19323,"journal":{"name":"Novartis Foundation Symposium","volume":"117 2","pages":"161-71; discussion 171-6, 207-10, 276-85"},"PeriodicalIF":0.0,"publicationDate":"2008-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/0470861193.CH13","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50774615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
To unravel the complex disease phenotype of heart failure, we are utilizing an integrative approach employing genomics, physiology, and mouse genetics to identify nodal pathways for specific physiological end points such as myocyte stretch activation responses, contractility and electrical conduction. A new class of genetic pathways for cardiac sudden death and associated arrhythmias has been based on transcription factors that control conduction system lineages, including HF1b/SP4 and NKX2.5. Previous studies have established that HF1b plays a critical role in conduction system lineage formation and the loss of HF1b leads to a confused electrophysiological identity in Purkinje and ventricular cell lineages, resulting in cardiac sudden death and marked tachy and brady arrhythmias. Utilizing Hf1b and Nkx2.5 floxed alleles, we now have identified the primary pathways which link these transcription factors with cardiac arrythmogenesis. Mice which harbour a neural crest restricted knockout of HF1b display marked arrhythmogenesis and conduction system defects, implicating neural crest cues in conduction system development and disease. Mice which harbour a ventricular-restricted knockout of Nkx2.5 display completely normal conduction at birth, but a hypoplastic atrioventricular (AV) node. During maturation, progressive complete heart block ensues, associated with a selective dropout of distal AV nodal cell lineages at the boundaries of the penetrating His bundle. Single cell analyses examining individual nodal cells within AV node of ventricular restricted Nkx2.5 knockout mice clearly document a cell autonomous requirement for NKX2.5 within AV nodal lineages per se. Micro-electrophysiological AV nodal mapping indicates a selective conduction defect at the boundary of the distal AV node and His bundle. HF1b and NKX2.5 reflect new cardiac cell non-autonomous and autonomous pathways for conduction system lineage defects and associated cardiac arrythmogenesis.
{"title":"Defects in cardiac conduction system lineages and malignant arrhythmias: developmental pathways and disease.","authors":"T. S. St Amand, Jonathan T. Lu, K. Chien","doi":"10.1002/0470868066.CH16","DOIUrl":"https://doi.org/10.1002/0470868066.CH16","url":null,"abstract":"To unravel the complex disease phenotype of heart failure, we are utilizing an integrative approach employing genomics, physiology, and mouse genetics to identify nodal pathways for specific physiological end points such as myocyte stretch activation responses, contractility and electrical conduction. A new class of genetic pathways for cardiac sudden death and associated arrhythmias has been based on transcription factors that control conduction system lineages, including HF1b/SP4 and NKX2.5. Previous studies have established that HF1b plays a critical role in conduction system lineage formation and the loss of HF1b leads to a confused electrophysiological identity in Purkinje and ventricular cell lineages, resulting in cardiac sudden death and marked tachy and brady arrhythmias. Utilizing Hf1b and Nkx2.5 floxed alleles, we now have identified the primary pathways which link these transcription factors with cardiac arrythmogenesis. Mice which harbour a neural crest restricted knockout of HF1b display marked arrhythmogenesis and conduction system defects, implicating neural crest cues in conduction system development and disease. Mice which harbour a ventricular-restricted knockout of Nkx2.5 display completely normal conduction at birth, but a hypoplastic atrioventricular (AV) node. During maturation, progressive complete heart block ensues, associated with a selective dropout of distal AV nodal cell lineages at the boundaries of the penetrating His bundle. Single cell analyses examining individual nodal cells within AV node of ventricular restricted Nkx2.5 knockout mice clearly document a cell autonomous requirement for NKX2.5 within AV nodal lineages per se. Micro-electrophysiological AV nodal mapping indicates a selective conduction defect at the boundary of the distal AV node and His bundle. HF1b and NKX2.5 reflect new cardiac cell non-autonomous and autonomous pathways for conduction system lineage defects and associated cardiac arrythmogenesis.","PeriodicalId":19323,"journal":{"name":"Novartis Foundation Symposium","volume":"170 2","pages":"260-70; discussion 271-5, 276-9"},"PeriodicalIF":0.0,"publicationDate":"2008-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/0470868066.CH16","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50779086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Recent studies have revealed that reducing sugars, such as glucose, react with proteins through non-enzymatic glycosylation to form irreversible, covalently cross-linked proteins known as advanced glycation endproducts (AGEs). Furthermore, it has been demonstrated that this naturally occurring process, accelerated in diabetics due to hyperglycaemia, impairs biological functions leading to cardiovascular disorders, as well as diabetic and age-related complications. Pharmaceutical intervention to prevent or reverse these complications have focused on inhibiting the formation of AGEs by compounds such as dimethyl-3-phenacylthiazolium chloride or breaking the glucose derived cross-links by selective cleavage. Intervention targeted at AGE cross-links in vivo offers a way to interfere with age-related changes of tissues.
{"title":"Pharmaceutical intervention of advanced glycation endproducts.","authors":"A. Cerami, P. Ulrich","doi":"10.1002/0470868694.CH16","DOIUrl":"https://doi.org/10.1002/0470868694.CH16","url":null,"abstract":"Recent studies have revealed that reducing sugars, such as glucose, react with proteins through non-enzymatic glycosylation to form irreversible, covalently cross-linked proteins known as advanced glycation endproducts (AGEs). Furthermore, it has been demonstrated that this naturally occurring process, accelerated in diabetics due to hyperglycaemia, impairs biological functions leading to cardiovascular disorders, as well as diabetic and age-related complications. Pharmaceutical intervention to prevent or reverse these complications have focused on inhibiting the formation of AGEs by compounds such as dimethyl-3-phenacylthiazolium chloride or breaking the glucose derived cross-links by selective cleavage. Intervention targeted at AGE cross-links in vivo offers a way to interfere with age-related changes of tissues.","PeriodicalId":19323,"journal":{"name":"Novartis Foundation Symposium","volume":"19 11","pages":"202-12; discussion 212-6, 217-20"},"PeriodicalIF":0.0,"publicationDate":"2008-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/0470868694.CH16","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50780244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2008-10-07DOI: 10.1002/9780470033449.CH14
S. Monticelli, K. Ansel, Dong U. Lee, A. Rao
Despite deriving from two different compartments of the immune system (myeloid and lymphoid respectively), Th2 cells and mast cells produce the same panel of cytokines, interleukin (IL)4, IL5 and IL13. We have compared the chromatin structure of the RAD50/IL13/IL4 locus in Th2 cells and mast cells. Th2 and mast cells display strong overlap in their patterns of DNase I hypersensitivity throughout this locus, except that the first intron of the IL13 gene (MCHS) is DNase I hypersensitive only in mast cells and the conserved non-coding sequence (CNS)-1 in the IL4/IL13 intergenic region is DNase I hypersensitive only in Th2 cells (explaining why cytokine expression is impaired in Th2 cells but not in mast cells of CNS-1-deleted mice). We have also examined the role of micro-RNAs (miRNAs) in the development and activation of mast cells and T cells. miRNAs are 21- to 25-nucleotide small RNAs that regulate gene expression posttranscriptionally by targeting protein-coding mRNAs. Using oligonucleotide arrays to analyse miRNA expression in murine T cells and mast cells, we have identified distinctive cell type-specific patterns of miRNA expression as well as changes related to differentiation and cell activation. We are studying the biological functions of selected miRNAs.
{"title":"Regulation of gene expression in mast cells: micro-rNA expression and chromatin structural analysis of cytokine genes.","authors":"S. Monticelli, K. Ansel, Dong U. Lee, A. Rao","doi":"10.1002/9780470033449.CH14","DOIUrl":"https://doi.org/10.1002/9780470033449.CH14","url":null,"abstract":"Despite deriving from two different compartments of the immune system (myeloid and lymphoid respectively), Th2 cells and mast cells produce the same panel of cytokines, interleukin (IL)4, IL5 and IL13. We have compared the chromatin structure of the RAD50/IL13/IL4 locus in Th2 cells and mast cells. Th2 and mast cells display strong overlap in their patterns of DNase I hypersensitivity throughout this locus, except that the first intron of the IL13 gene (MCHS) is DNase I hypersensitive only in mast cells and the conserved non-coding sequence (CNS)-1 in the IL4/IL13 intergenic region is DNase I hypersensitive only in Th2 cells (explaining why cytokine expression is impaired in Th2 cells but not in mast cells of CNS-1-deleted mice). We have also examined the role of micro-RNAs (miRNAs) in the development and activation of mast cells and T cells. miRNAs are 21- to 25-nucleotide small RNAs that regulate gene expression posttranscriptionally by targeting protein-coding mRNAs. Using oligonucleotide arrays to analyse miRNA expression in murine T cells and mast cells, we have identified distinctive cell type-specific patterns of miRNA expression as well as changes related to differentiation and cell activation. We are studying the biological functions of selected miRNAs.","PeriodicalId":19323,"journal":{"name":"Novartis Foundation Symposium","volume":"271 1","pages":"179-87; discussion 187-90, 198-9"},"PeriodicalIF":0.0,"publicationDate":"2008-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"51135188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The marked variability in the development of chronic obstructive pulmonary disease (COPD) in response to cigarette smoking has been known for decades, but severe alpha 1-antitrypsin deficiency (PI Z) remains the only proven genetic risk factor for COPD. With cigarette smoking, PI Z subjects tend to develop more severe pulmonary impairment at an earlier age than non-smoking PI Z individuals. However, PI Z individuals exhibit wide variability in pulmonary function impairment, even among individuals with similar smoking histories. Therefore, other genes and environmental exposures are also likely involved. The role of heterozygosity for the Z allele as a risk factor for COPD remains controversial, but accumulating evidence suggests that at least some PI MZ individuals are at increased risk of developing airflow obstruction. In individuals without alpha 1-antitrypsin deficiency, familial aggregation of COPD has been reported in several studies. To study novel genetic determinants of COPD, our research group enrolled 44 severe, early-onset COPD probands (FEV1 < 40%, age < 53 yrs, non-PI Z) and 266 of their relatives. A marked female predominance was noted among the early-onset COPD probands. In addition, increased risk to current or ex-smoking first-degree relatives of early-onset COPD probands for reduced FEV1, chronic bronchitis and spirometric bronchodilator responsiveness has been demonstrated. These data strongly support the genetic basis for the development of COPD and the potential for gene-by-environment interaction. A variety of studies have examined candidate gene loci with association studies, comparing the distribution of variants in genes hypothesized to be involved in the development of COPD in COPD patients and control subjects. For most genetic loci which have been tested, there have been inconsistent results. Genetic heterogeneity could contribute to difficulty in replicating associations between studies. In addition, case-control association studies are susceptible to supporting associations based purely on population stratification, which can result from incomplete matching between cases and controls--including differences in ethnicity. No association studies in COPD have been reported which used family-based controls, a study design which is immune to such population stratification effects. More importantly, no linkage studies have been published in COPD to identify regions of the genome which are likely to contain COPD susceptibility genes--regions in which association studies are likely to be more productive.
{"title":"Genetics of chronic obstructive pulmonary disease.","authors":"E. Silverman","doi":"10.1002/0470868678.CH4","DOIUrl":"https://doi.org/10.1002/0470868678.CH4","url":null,"abstract":"The marked variability in the development of chronic obstructive pulmonary disease (COPD) in response to cigarette smoking has been known for decades, but severe alpha 1-antitrypsin deficiency (PI Z) remains the only proven genetic risk factor for COPD. With cigarette smoking, PI Z subjects tend to develop more severe pulmonary impairment at an earlier age than non-smoking PI Z individuals. However, PI Z individuals exhibit wide variability in pulmonary function impairment, even among individuals with similar smoking histories. Therefore, other genes and environmental exposures are also likely involved. The role of heterozygosity for the Z allele as a risk factor for COPD remains controversial, but accumulating evidence suggests that at least some PI MZ individuals are at increased risk of developing airflow obstruction. In individuals without alpha 1-antitrypsin deficiency, familial aggregation of COPD has been reported in several studies. To study novel genetic determinants of COPD, our research group enrolled 44 severe, early-onset COPD probands (FEV1 < 40%, age < 53 yrs, non-PI Z) and 266 of their relatives. A marked female predominance was noted among the early-onset COPD probands. In addition, increased risk to current or ex-smoking first-degree relatives of early-onset COPD probands for reduced FEV1, chronic bronchitis and spirometric bronchodilator responsiveness has been demonstrated. These data strongly support the genetic basis for the development of COPD and the potential for gene-by-environment interaction. A variety of studies have examined candidate gene loci with association studies, comparing the distribution of variants in genes hypothesized to be involved in the development of COPD in COPD patients and control subjects. For most genetic loci which have been tested, there have been inconsistent results. Genetic heterogeneity could contribute to difficulty in replicating associations between studies. In addition, case-control association studies are susceptible to supporting associations based purely on population stratification, which can result from incomplete matching between cases and controls--including differences in ethnicity. No association studies in COPD have been reported which used family-based controls, a study design which is immune to such population stratification effects. More importantly, no linkage studies have been published in COPD to identify regions of the genome which are likely to contain COPD susceptibility genes--regions in which association studies are likely to be more productive.","PeriodicalId":19323,"journal":{"name":"Novartis Foundation Symposium","volume":"5 13","pages":"45-58; discussion 58-64"},"PeriodicalIF":0.0,"publicationDate":"2008-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/0470868678.CH4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50779848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
From Spearman's famous 1904 paper to Carroll's recent book on factor analytic results from a multitude of studies, there has been one consistent conclusion: 'g', or general intelligence, is the factor that defines the phenotype for intellectual functioning. It is no overstatement to say that g is undoubtedly the most important psychological construct discovered in this century. It predicts more and is implicated in a wider range of behaviour than any other psychological construct. The empirical support for g is extensive and overwhelming. It would seem that g is the perfect phenotypic definition of intelligence. I argue that it is not the perfect phenotype. If we are to understand intelligence, we need to define a new, more elaborate definition of intelligence taking g as the starting place. It must be remembered that g is a statistical abstraction. Current formulations of g are largely silent about the composition of g. I argue that g is actually made of further separable basic cognitive processes and does not represent a single underlying entity. These basic cognitive processes are integrated into a complex system in the brain that makes them difficult to identify. None the less, until these basic processes are identified and related to brain function there are a number of findings that cannot be explained and this will inhibit scientific progress.
{"title":"General intelligence and the definition of phenotypes.","authors":"D. Detterman","doi":"10.1002/0470870850.CH9","DOIUrl":"https://doi.org/10.1002/0470870850.CH9","url":null,"abstract":"From Spearman's famous 1904 paper to Carroll's recent book on factor analytic results from a multitude of studies, there has been one consistent conclusion: 'g', or general intelligence, is the factor that defines the phenotype for intellectual functioning. It is no overstatement to say that g is undoubtedly the most important psychological construct discovered in this century. It predicts more and is implicated in a wider range of behaviour than any other psychological construct. The empirical support for g is extensive and overwhelming. It would seem that g is the perfect phenotypic definition of intelligence. I argue that it is not the perfect phenotype. If we are to understand intelligence, we need to define a new, more elaborate definition of intelligence taking g as the starting place. It must be remembered that g is a statistical abstraction. Current formulations of g are largely silent about the composition of g. I argue that g is actually made of further separable basic cognitive processes and does not represent a single underlying entity. These basic cognitive processes are integrated into a complex system in the brain that makes them difficult to identify. None the less, until these basic processes are identified and related to brain function there are a number of findings that cannot be explained and this will inhibit scientific progress.","PeriodicalId":19323,"journal":{"name":"Novartis Foundation Symposium","volume":"26 4","pages":"136-44; discussion 144-8"},"PeriodicalIF":0.0,"publicationDate":"2008-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/0470870850.CH9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50786699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mesenchymal stem cells have the capacity to differentiate into a variety of connective tissue cells including bone, cartilage, tendon, muscle and adipose tissue. These multipotent cells have been isolated from bone marrow and from other adult tissues including skeletal muscle, fat and synovium. Because of their multipotentiality and capacity for self renewal adult stem cells may represent units of active regeneration of tissues damaged as a result of trauma or disease. In certain degenerative diseases such as osteoarthritis (OA) stem cells are depleted, and have reduced proliferative capacity and reduced ability to differentiate. The delivery of stem cells to these individuals may therefore enhance repair or inhibit the progressive destruction of the joint. We have developed methods for the delivery of mesenchymal stem cell preparations taken from bone marrow to the injured knee joint. This treatment has the potential to stimulate regeneration of cartilage and retard the progressive destruction of the joint that typically occurs following injury.
{"title":"Mesenchymal stem cell therapy in joint disease.","authors":"F. Barry","doi":"10.1002/0470867973.CH7","DOIUrl":"https://doi.org/10.1002/0470867973.CH7","url":null,"abstract":"Mesenchymal stem cells have the capacity to differentiate into a variety of connective tissue cells including bone, cartilage, tendon, muscle and adipose tissue. These multipotent cells have been isolated from bone marrow and from other adult tissues including skeletal muscle, fat and synovium. Because of their multipotentiality and capacity for self renewal adult stem cells may represent units of active regeneration of tissues damaged as a result of trauma or disease. In certain degenerative diseases such as osteoarthritis (OA) stem cells are depleted, and have reduced proliferative capacity and reduced ability to differentiate. The delivery of stem cells to these individuals may therefore enhance repair or inhibit the progressive destruction of the joint. We have developed methods for the delivery of mesenchymal stem cell preparations taken from bone marrow to the injured knee joint. This treatment has the potential to stimulate regeneration of cartilage and retard the progressive destruction of the joint that typically occurs following injury.","PeriodicalId":19323,"journal":{"name":"Novartis Foundation Symposium","volume":"1 4","pages":"86-96; discussion 96-102, 170-4, 239-41"},"PeriodicalIF":0.0,"publicationDate":"2008-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/0470867973.CH7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50778346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fish comprise the largest group of extant vertebrates with approximately 25,000 known species. Some of these species are exceptional among vertebrates because they can change sex as adults. This observation raises ultimate questions about what selective forces led to the evolution of sex-changing ability and raises proximate questions about what mechanisms could account for this process. Sex change can be either from female to male (protogyny) or the reverse (protandry). In either case, the actual process of sex reversal requires reorganization of many critically important physiological systems from transformation of the gonads to modification of the neural and hormonal control systems. All of these changes require an individual animal to initiate the process based on information gleaned from the social situation. This is all the more remarkable because the information could be as simple as size discrimination or as complex as detecting subtle behavioural signals. Although it is self-evident that the brain controls behaviour, clearly behaviour can also 'control' the brain. How does behaviour cause changes in the brain? The work described here links molecular events with organismal behaviour by using an African cichlid fish model system in which social behaviours regulate reproduction. These animals have a complex social system based on the behaviour of two distinct classes of males, those with territories and those without. Changes in social status produced by behavioural interactions cause changes in neurons and endocrine responses. Surprisingly, growth rate is also regulated by social status and prior social history. Discovering how relevant social information is transduced into physiological processes requiring cellular and molecular action presents a major challenge.
{"title":"Social regulation of the brain: sex, size and status.","authors":"R. Fernald","doi":"10.1002/0470868732.CH14","DOIUrl":"https://doi.org/10.1002/0470868732.CH14","url":null,"abstract":"Fish comprise the largest group of extant vertebrates with approximately 25,000 known species. Some of these species are exceptional among vertebrates because they can change sex as adults. This observation raises ultimate questions about what selective forces led to the evolution of sex-changing ability and raises proximate questions about what mechanisms could account for this process. Sex change can be either from female to male (protogyny) or the reverse (protandry). In either case, the actual process of sex reversal requires reorganization of many critically important physiological systems from transformation of the gonads to modification of the neural and hormonal control systems. All of these changes require an individual animal to initiate the process based on information gleaned from the social situation. This is all the more remarkable because the information could be as simple as size discrimination or as complex as detecting subtle behavioural signals. Although it is self-evident that the brain controls behaviour, clearly behaviour can also 'control' the brain. How does behaviour cause changes in the brain? The work described here links molecular events with organismal behaviour by using an African cichlid fish model system in which social behaviours regulate reproduction. These animals have a complex social system based on the behaviour of two distinct classes of males, those with territories and those without. Changes in social status produced by behavioural interactions cause changes in neurons and endocrine responses. Surprisingly, growth rate is also regulated by social status and prior social history. Discovering how relevant social information is transduced into physiological processes requiring cellular and molecular action presents a major challenge.","PeriodicalId":19323,"journal":{"name":"Novartis Foundation Symposium","volume":"2 3","pages":"169-84; discussion 184-6, 203-6, 253-7"},"PeriodicalIF":0.0,"publicationDate":"2008-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/0470868732.CH14","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50782423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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