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Results for “Longitudinal phenotype”

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At least 127 records · Page 7Linked to original sources
PubMed1994

Effects of therapy with interferon-alpha on peripheral blood lymphocyte subsets and NK activity in patients with chronic hepatitis C.

Longitudinal changes in lymphocyte subpopulations, including total and activated T cells, B cells, and NK cells as well as NK activity and 2',5'-oligoadenylate synthetase (2'5' AS) levels were determined in peripheral blood before, during, and after therapy with human recombinant interferon-alpha (HurIFN-alpha) in 39 patients with serologically and biopsy-confirmed chronic hepatitis C. Immunologic data obtained at baseline and during IFN-alpha administration were correlated with the clinical response to IFN-alpha therapy defined as a normalization of the serum alanine aminotransferase level. There were 23 responders (R) and 13 nonresponders (NR) to IFN-alpha and 3 patients were not evaluable. Prior to the use of IFN-alpha, the patients tended to have higher numbers of activated (DR+) T and NK cells but a lower number of CD3+CD25+ T cells than normal controls. During IFN-alpha therapy, highly significant induction of 2'5'AS was observed. The numbers of circulating WBC, total lymphocytes, and T and B cells were reduced during IFN-alpha therapy. In contrast, both the absolute number and percentage of activated CD3+CD25+ and CD4+DR+ T cells increased in response to the IFN-alpha therapy. The percentage of activated CD56+DR+ NK cells was also significantly elevated over the pretreatment baseline. IFN-alpha therapy had no effect on NK activity in peripheral blood mononuclear cells. No differences in the immunologic profile of R vs NR were noted, except that the number of IL2R+ T cells was increased transiently early during IFN-alpha therapy but only in the NR group. It was not possible to reliably discriminate between R vs NR to IFN-alpha therapy on the basis of longitudinal changes in the phenotype or function of immune effector cells.

2',5'-Oligoadenylate Synthetase↗
PubMed2004

Field performance of chitinase transgenic silver birches (Betula pendula): resistance to fungal diseases.

A field trial of 15 transgenic birch lines expressing a sugar beet chitinase IV gene and the corresponding controls was established in southern Finland to study the effects of the level of sugar beet chitinase IV expression on birch resistance to fungal diseases. The symptoms caused by natural infections of two fungal pathogens, Pyrenopeziza betulicola (leaf spot disease) and Melampsoridium betulinum (birch rust), were analysed in the field during a period of 3 years. The lines that had shown a high level of sugar beet chitinase IV mRNA accumulation in the greenhouse also showed high sugar beet chitinase IV expression after 3 years in the field. The level of sugar beet chitinase IV expression did not significantly improve the resistance of transgenic birches to leaf spot disease. Instead, some transgenic lines were significantly more susceptible to leaf spot than the controls. The level of sugar beet chitinase IV expression did have an improving effect on most parameters of birch rust; the groups of lines showing high or intermediate transgene expression were more resistant to birch rust than those showing low expression. This result indicates that the tested transformation may provide a tool for increasing the resistance of silver birch to birch rust.

Analysis of Variance↗
PubMed2005

Testing models of thalamic dysfunction in schizophrenia using neuroimaging.

Neural models of schizophrenia have implicated the thalamus in deficits of early sensory processing and multimodal integration. We have reviewed the existing neuroimaging literature for evidence in support of models that propose abnormalities of thalamic relay nuclei, the mediodorsal thalamic nucleus, and large-scale cortico-thalamic networks. Thalamic volume reduction was found in some but not all studies. Studies of the early stages of schizophrenia suggest that thalamic volume reduction is present early in the course of the illness. Functional imaging studies have revealed task related abnormalities in several cortical and subcortical areas including the thalamus, suggesting a disruption of distributed thalamocortical networks. Chemical imaging studies have provided evidence for a loss of thalamic neuronal integrity in schizophrenia. There is, at present, inadequate data to support the hypothesis that schizophrenia is associated with abnormalities of sensory relay or association nuclei. There is evidence for a perturbation of cortico-thalamic networks, but further research is needed to elucidate the underlying mechanisms at the cellular and systems levels. The challenges ahead include better delineation of thalamic structure and function in vivo, the combination of genetic and imaging techniques to elucidate the genetic contributions to a thalamic phenotype of schizophrenia, and longitudinal studies of thalamic structure and function.

Animals↗
PubMed2001

Sickle cell disease: current clinical management.

The phenotypic expression of sickle cell disease (SCD) varies greatly among patients and longitudinally in the same patient. The phenotype influences all aspects of the life of affected individuals including social interactions, intimate relationships, family relations, education, employment, and spirituality. The clinical, manifestations of SCD are protean and fall into three major categories: (1) anemia and its sequelae; (2) pain and related issues; and (3) end-organ failure including infection. This review will emphasize the pathophysiology and management of sickle cell pain, as well as organ failure and its management.

Anemia, Sickle Cell↗
PubMed2003

Pathways to a robust immune response in the elderly.

Circumstantial evidence suggests that infectious disease is the major cause of morbidity and mortality in the elderly, and immune-system dysfunction may contribute to this finding. Because innate and humoral immunity seem to be relatively unaffected by aging and because the T-cell compartment shows marked age-associated alterations, this article focuses on the association between T cells and aging. Longitudinal studies suggest that immune parameters, which predominantly are related to T cells, can be clustered to yield an IRP that is predictive of mortality in the elderly. Determining the IRP also may be helpful in younger individuals, particularly those under chronic antigenic stress (eg, patients with cancer or chronic infections) who experience premature aging of the immune system. Some changes in T cells can be modeled in clonal cultures in vitro to discover new biomarkers of immune aging. These biomarkers, which need to be validated in vivo, could be used to refine IRP. Interventions to selectively target changes that are identified as part of IRP may improve the health and quality of life of the elderly, reduce healthcare costs, and avoid potential unwanted side effects of global intervention approaches, such as triggering or exacerbating autoimmunity and inflammation.

Aged↗
PubMed2006

A common genetic factor explains the association between psychopathic personality and antisocial behavior.

BACKGROUND: Both psychopathic personality traits and antisocial behavior are influenced by genetic as well as environmental factors. However, little is known about how genetic and environmental factors contribute to the associations between the psychopathic personality traits and antisocial behavior. METHOD: Data were drawn from a longitudinal population-based twin sample including all 1480 twin pairs born in Sweden between May 1985 and December 1986. The twins responded to mailed self-report questionnaires at two occasions: 1999 (twins 13-14 years old), and 2002 (twins 16-17 years old). RESULTS: A common genetic factor loaded substantially on both psychopathic personality traits and antisocial behavior, whereas a common shared environmental factor loaded exclusively on antisocial behavior. CONCLUSIONS: The genetic overlap between psychopathic personality traits and antisocial behavior may reflect a genetic vulnerability to externalizing psychopathology. The finding of shared environmental influences only in antisocial behavior suggests an etiological distinction between psychopathic personality dimensions and antisocial behavior. Knowledge about temperamental correlates to antisocial behavior is important for identification of susceptibility genes, as well as for possible prevention through identification of at-risk children early in life.

Adolescent↗
PubMed2003

Yield stability in Coffea canephora from diallel mating designs monitored for 14 years.

The genetic parameters of several agronomic traits were estimated in Coffea canephora in a triangular diallel with six parents and in a partial diallel with 18 parents. The yield data came from harvests obtained over 14 years divided into an initial 6-year cycle, a second cycle of 5 years after cutting back and a third cycle of 3 years after topping. Risk incidence was also observed over several years. The general combining abilities (GCA) were the principal sources of variation for the various traits considered. Parents derived from the Yangambi selections (Democratic Republic of Congo) proved to be best for yields in the three cropping cycles. The rank correlations between the GCA of the various traits indicated that first-cycle production was still not enough to predict the GCA for yield over 14 years. Susceptibility to leaf anthracnose and to drought could lead to modifications in successive classifications, with a more significant impact on production during the first cycle. The differences in susceptibility to Coffee Berry Borers had an impact on yield, which increased in line with coffee tree age. There was a rather good relation between inherent values and values in parent combinations and it was thus possible to choose parents on their own performance.

Africa South of the Sahara↗
PubMed2005

Interleukin-12 and -18 levels in peritoneal dialysate effluent correlate with the outcome of peritonitis in patients undergoing peritoneal dialysis: implications for the Type I/Type II T-cell immune response.

BACKGROUND: We previously showed that a positive impact of peritoneal defense response on the outcome of peritoneal dialysis (PD)-related peritonitis is characterized by an increased pattern of peritoneal CD4/CD8 T-cell ratio with a predominant CD4(+)-T helper subtype 1 phenotype. To further explore longitudinal changes in peritoneal immunity during PD-related peritonitis, we examined the production of interleukin 12 (IL-12), IL-18, and interferon gamma (IFN-gamma) in peritoneal dialysate effluent (PDE) and kinetic expression of the transcription factors T box expressed in T cells (T-bet) and guanine adenine thymine adenine (GATA) binding protein 3 (GATA-3) in peritoneal T cells during peritonitis. Correlations between these observations and responses to antibiotics were analyzed. METHODS: IL-12, IL-18, and IFN-gamma protein and IFN-gamma, T-bet, and GATA-3 messenger RNA (mRNA) were measured in PDE during various phases of peritonitis in 40 patients undergoing PD. Patients were divided into 2 groups according to whether they had a rapid versus delayed response to antibiotic treatment. RESULTS: In the early phase of peritonitis, IL-12, IL-18, and IFN-gamma levels in PDE were significantly greater in the rapid-response group (P < 0.05). Changes in peritoneal IL-12 and IL-18 levels preceded changes in IFN-gamma levels. The kinetics of IFN-gamma, T-bet, and GATA-3 mRNA expression in peritoneal T cells, measured by means of real-time polymerase chain reaction, differed between the 2 groups. In the rapid-response group, IFN-gamma and T-bet mRNA expression increased, whereas that of GATA-3 decreased over time. Results were opposite in the delayed-response group, with IFN-gamma and T-bet levels decreasing and GATA-3 levels increasing over time. CONCLUSION: These data suggest that local IL-12 and IL-18 production is part of a protective early immune response to PD-related peritonitis. High IL-12 and IL-18 levels in PDE during the early phase of peritonitis correlated with a predominant type 1 immune response and favorable outcome.

Adult↗
PubMed2003

The malignant clone in Waldenstrom's macroglobulinemia.

The unique IgM VDJ sequence that characterizes the malignant clone in Waldenstrom's macroglobulinemia (WM), termed clonotypic, was identified for 12 WM patients. The majority of WM patients (92%) had a clonotypic IgM from the VH3 family, with predominantly long CDR3 regions, characteristic of those found in antigen-stimulated populations. Clonotypic IgM transcripts were detected in both blood and bone marrow (BM), clearly identifying a blood-borne compartment of WM. Abnormal numbers of CD20(+) B cells were usually detectable and expressed surface IgM. In most cases these cells also expressed surface IgD. Most WM patients lacked detectable CD138(+) plasma cells in either blood or BM. Longitudinal analysis suggests that phenotypic identification of B cells in blood of WM patients is insufficient for monitoring disease. Although serum IgM had decreased and clonotypic transcripts were very weak for one patient, the number of CD20(+) B cells increased dramatically. The lack of clonotypic transcripts suggests that the majority of these circulating B cells were polyclonal and were not part of the WM clone, indicating that monitoring of clonotypic IgM provides the most accurate identifier of WM cells.

Antigens, CD20↗
PubMed2000

Reduced body weight, adipose tissue, and leptin levels despite increased energy intake in female mice lacking acylation-stimulating protein.

Acylation-stimulating protein (ASP) is a potent lipogenic protein produced by adipocytes. In vitro studies have shown that ASP increases triglyceride synthesis and glucose transport in both murine and human adipocytes. Our initial study indicated that complement C3-deficient (-/-) mice (and, therefore, ASP deficient) demonstrated altered dietary postprandial triglyceride clearance. In the present study we examined the phenotype of female mice longitudinally on different diets. Female C3(-/-) mice on both low (10% of energy) and high (40% of energy) fat diets displayed an average reduction in total body weight of 10.1+/-0.5% (P < 0.0003, by ANOVA) compared with the C3(+/+) littermates. Reductions in white adipose tissue mass accounted for most of this weight difference (59% reduction; P < 0.01 on low fat diet). Plasma leptin levels were significantly reduced in C3(-/-) mice on both high (P < 0.001) and low fat diets (P < 0.01). This reduction was significant even after adjusting for the reduced body weight and body fat (P < 0.001). Leptin reductions in the C3(-/-) were greater on the high fat diet and were associated with increased food intake (18+/-2% increase; P < 0.001). Furthermore, there was a decrease in basal glucose levels and basal insulin levels [12.8% decrease in glucose at 14 weeks (HF; P < 0.05) and 41% decrease in insulin at 26 weeks (HF; P < 0.05)]. These in vivo experiments demonstrate that female mice lacking ASP have marked alterations of body weight, adiposity, plasma leptin, and plasma insulin levels. Decreased adiposity and leptin levels occurred in the ASP-deficient animals despite increased energy intake, suggesting that energy expenditure was elevated in these animals. Thus, ASP appears to have an important role in the regulation of energy balance in mice.

Adipose Tissue↗
PubMed2002

A novel linker histone-like protein is associated with cytoplasmic filaments in Caenorhabditis elegans.

The histone H1 complement of Caenorhabditis elegans contains a single unusual protein, H1.X. Although H1.X possesses the globular domain and the canonical three-domain structure of linker histones, the amino acid composition of H1.X is distinctly different from conventional linker histones in both terminal domains. We have characterized H1.X in C. elegans by antibody labeling, green fluorescent protein fusion protein expression and RNA interference. Unlike normal linker histones, H1.X is a cytoplasmic as well as a nuclear protein and is not associated with chromosomes. H1.X is most prominently expressed in the marginal cells of the pharynx and is associated with a peculiar cytoplasmic cytoskeletal structure therein, the tonofilaments. Additionally H1.X::GFP is expressed in the cytoplasm of body and vulva muscle cells, neurons, excretory cells and in the nucleoli of embryonic blastomeres and adult gut cells. RNA interference with H1.X results in uncoordinated and egg laying defective animals, as well as in a longitudinally enlarged pharynx. These phenotypes indicate a cytoplasmic role of H1.X in muscle growth and muscle function.

Animals↗
PubMed2002

Nucleotide pyrophosphatase gene polymorphism associated with ossification of the posterior longitudinal ligament of the spine.

Ossification of the posterior longitudinal ligament (OPLL) of the spine is a disease that causes paralysis by compressing the spinal cord. Based on the fact that the nucleotide pyrophosphatase (Npps) gene is responsible for ectopic ossification in ttw, an OPLL model mouse, the possibility was explored whether the human NPPS gene is associated with susceptibility to and severity of OPLL. First, we screened for single-nucleotide polymorphisms (SNPs) in the human NPPS locus using selected 25 OPLL patients with young onset (< 35 years old) or severe ossification (> 10 ossified vertebrae), and identified three novel SNPs in the locus. A case-control association study between 180 OPLL patients and 265 non-OPLL controls showed that one of these SNPs, IVS15-14T --> C substitution, was more frequently observed in OPLL patients (p = 0.022), especially in those with severe ossification (p < 0.0001) and young onset (p = 0.002), than in controls. A stratified study with the number of ossified vertebrae in OPLL patients revealed that IVS15-14T --> C substitution (p = 0.013) as well as young onset (p = 0.046) and female sex (p = 0.006) were associated with severe ossification. We conclude that the IVS15-14T --> C substitution in the human NPPS gene is associated not only with susceptibility to, but also with severity of OPLL.

Adult↗
PubMed1999

Genetic markers of atopy in infancy: results from the German Multicenter Allergy Study.

Genetic studies of atopy-associated traits require unambiguous phenotypes to avoid both type 1 and 2 errors. The German Multicenter Allergy Study has provided a birth cohort with longitudinally well defined and stable phenotypes. We summarize data on candidate gene studies on chromosomes 12q, 5q, and 13q using high total IgE and atopic dermatitis (AD) as the most common atopy associated phenotypes in early childhood. We also present data on a functional RANTES promoter polymorphism that we recently identified. A significantly higher frequency of the mutant allele was seen in individuals of African descent compared to Caucasian subjects. In addition, an association of the polymorphism with AD could be demonstrated in the MAS cohort. Although the statistical approaches are limited, the MAS cohort has provided a valuable population for candidate gene studies in atopy.

Chemokine CCL5↗
PubMed1993

The role of genetics in defining reference values and health status.

Since its establishment, the Center for Preventive Medicine in Vandoeuvre-les-Nancy, France, performed specific studies on healthy humans, and its approach was very useful for defining reference values. Prevention should extend its interest to chronic diseases. The majority of important adult disorders are partially genetically determined. Genetic markers are also useful as exclusion or as partition criteria in the production of reference values. Results are presented that were obtained for apolipoproteins E, B and AIV, frequencies of these polymorphisms in the Lorraine population, and relationships between these polymorphisms and lipid metabolism-related parameters. Health checkup centers, in particular those involved in family screening, are well suited for resembling many data concerning environmental factors: tobacco consumption, alimentation habits, or alcohol and drug consumption. Simultaneous determination of genetic markers could allow the determination of an individual's susceptibility or resistance to developing a disease and to prepare a preventive action.

Environmental Exposure↗
PubMed2025

Patient stratification by genetic risk in Alzheimer's disease is only effective in the presence of phenotypic heterogeneity.

Case-only designs in longitudinal cohorts are a valuable resource for identifying disease-relevant genes, pathways, and novel targets influencing disease progression. This is particularly relevant in Alzheimer's disease (AD), where longitudinal cohorts measure disease "progression," defined by rate of cognitive decline. Few of the identified drug targets for AD have been clinically tractable, and phenotypic heterogeneity is an obstacle to both clinical research and basic science. In four cohorts (n = 7241), we performed genome-wide association studies (GWAS) and Mendelian randomization (MR) to discover novel targets associated with progression and assess causal relationships. We tested opportunities for patient stratification by deriving polygenic risk scores (PRS) for AD risk and severity and tested the value of these scores in predicting progression. Genome-wide association studies identified no loci associated with progression at genome-wide significance (&#x3b1; = 5&#xd7;10-8); MR analyses provided no significant evidence of an association between cognitive decline in AD patients and protein levels in brain, cerebrospinal fluid (CSF), and plasma. Polygenic risk scores for AD risk did not reliably stratify fast from slow progressors; however, a deeper investigation found that APOE &#x3b5;4 status predicts amyloid-&#x3b2; and tau positive versus negative patients (odds ratio for an additional APOE &#x3b5;4 allele = 5.78 [95% confidence interval: 3.76-8.89], P<0.001) when restricting to a subset of patients with available CSF biomarker data. These results provided no evidence for large-effect, common-variant loci involved in the rate of memory decline, suggesting that patient stratification based on common genetic risk factors for progression may have limited utility. Where clinically relevant biomarkers suggest diagnostic heterogeneity, there is evidence that a priori identified genetic risk factors may have value in patient stratification. Mendelian randomization was less tractable due to the lack of large-effect loci, and future analyses with increased samples sizes are needed to replicate and validate our results.

Alzheimer Disease↗
PubMed1988

Causes and effects of high blood pressure: a longitudinal approach to genetic cosegregational analysis.

Numerous biochemical and physiological phenotypic differences exist between genetically normotensive and hypertensive rats. Only some of these differences, however, are likely to be related to the primary mechanisms causing high blood pressure. Others, and perhaps the majority, will be the result of either the secondary effects of hypertension or the result of incidental genetic differences between the strains that bear no relationship to the difference in blood pressure. Cosegregational analysis by cross-breeding normotensive and hypertensive strains permits the identification of phenotypes that are genetically linked to high blood pressure. However, cosegregational analyses are still prone to the confounding effects of hypertension per se, which can obscure important phenotypic traits and might even mimic Mendelian inheritance of phenotypes by producing qualitative shifts in gene expression. This paper discusses a longitudinal approach to genetic analysis designed to increase the sensitivity with which primary causes of high blood pressure are identified, by beginning the analysis during the development of high blood pressure. At this stage, phenotypic abnormalities causing blood pressure to rise are most likely to be present, and the blood pressure elevation is small so that the confounding effects of elevated arterial pressure are minimized.

Animals↗
PubMed1981

Heterozygous alpha 1-antitrypsin deficiency: a longitudinal lung function study.

alpha 1-antitrypsin phenotypes were determined in 906 adults from an entire community; 4.9 percent were heterozygotes (Pi MZ) for severe deficiency and 8 percent were heterozygotes (Pi MS) for mild deficiency. Lung function both in cross-section and over a period of three years was examined in those subjects with the two heterozygote deficiency phenotypes and compared with the lung function of those with the normal Pi M phenotype. FVC and FEV1 were standardised for age, sex, height, race, smoking habit and quantum, and respiratory symptoms. Using techniques of multivariate analysis and rigorous matched pairs there was no evidence of a deterioration in lung function in Pi MS or Pi MZ subjects. The tests used did not exclude the possibility of minor alveolar abnormalities but the results do allow the confident counselling of heterozygotes that they can look forward to full respiratory health.

Adult↗