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Results for “imaging genetics”

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At least 181 records · Page 10Linked to original sources
PubMed2006

Relationship of hepatic functional imaging to irinotecan pharmacokinetics and genetic parameters of drug elimination.

PURPOSE: The marked variability of irinotecan (Ir) clearance warrants individualized dosing based on hepatic drug handling. The aims of this trial were to identify parameters from functional hepatic nuclear imaging (HNI) that correlate with (1) Ir pharmacology, and (2) single-nucleotide polymorphisms (SNPs) for the ABCB1 (P-glycoprotein) and UGT-1A1 genes, known to influence Ir handling. METHODS: Patients underwent genotyping for ABCB1 SNPs and UTUGT-1A1*28 carriage and HNI with 99mTc-DIDA (acetanilidoiminodiacetic acid)/99mTc-DISIDA (disofenin) and MIBI (99mTc-sestamibi) scans, probes for biliary transport proteins ABCC1 and -2, and ABCB1 function. HNI data were analyzed by noncompartmental and deconvolutional analysis to provide hepatic extraction and biliary excretion parameters. Patients received Ir, fluorouracil, and folinic acid using a weekly x2, every-3-weeks schedule. Plasma was taken for Ir and SN-38 analysis on day 1, cycle 1. RESULTS: Of the 21 patients accrued, Ir pharmacokinetics data were obtained from 16 patients. 99mTc-DIDA/DISIDA percent retention at 1 hour (1-hour RET) correlated to baseline serum bilirubin (P = .008). Both 99mTc-DIDA/DISIDA and MIBI 1-hour RET correlated with SN-38 area under the curve (AUC; P < .01). On multiple regression analysis, SN-38 AUC = -215 + 18.68 x bilirubin + 4.27 x MIBI 1-hour RET (P = .009, R2 = 44.2%). HNI parameters did not correlate with Ir toxicity or UGT1A1*28 carriage. MIBI excretion was prolonged in patients with the ABCB1 exon 26 TT variant allele relative to wild-type (P = .015). CONCLUSION: Functional imaging of hepatic uptake and excretory pathways may have potential to predict Ir pharmacokinetics. Evaluation of a larger cohort as well as polymorphisms in other biliary transporters and UGT1A1 alleles is warranted.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2006

Next-generation optical technologies for illuminating genetically targeted brain circuits.

Emerging technologies from optics, genetics, and bioengineering are being combined for studies of intact neural circuits. The rapid progression of such interdisciplinary "optogenetic" approaches has expanded capabilities for optical imaging and genetic targeting of specific cell types. Here we explore key recent advances that unite optical and genetic approaches, focusing on promising techniques that either allow novel studies of neural dynamics and behavior or provide fresh perspectives on classic model systems.

Animals↗
PubMed2006

Serotonin function in panic disorder: important, but why?

The essential role of serotonin (5-hydroxytryptamine (5-HT)) system in the neurobiology and pharmacotherapy of panic disorder (PD) continues to be a topic of intensive interdisciplinary research. Interest in the involvement of 5-HT in PD has been fuelled by clinical studies demonstrating that medications increasing the synaptic availability of 5-HT, such as selective 5-HT re-uptake inhibitors, are effective in the treatment of PD. Rival theories of 5-HT deficiency vs excess have attempted to explain the impact of 5-HT function in PD. In the past decade, knowledge of the role of 5-HT in the neurobiology of PD has expanded dramatically due to much new research including experimental, treatment, brain-imaging, and genetic studies. The current review attempts to summarize the new data and their implications. The challenge and treatment studies generally confirm the specific inhibitory influence of 5-HT on panicogenesis. The brain-imaging studies in PD patients demonstrate functional and clinically relevant alterations in various elements of 5-HT system affecting the neurocircuitry of panic. The findings of genetic association studies suggest that certain 5-HT-related genes may contribute to the susceptibility to PD; however, these data are rather limited and inconsistent. It appears that, even if not the primary etiological factor in PD, the 5-HT function conveys important vulnerability, as well as adaptive factors. A better understanding of these processes may be critical in achieving progress in the treatment of patients suffering from PD.

Animals↗
PubMed2001

Congenital disorder of glycosylation type Ia: benign clinical course in a new genetic variant.

The congenital disorders of glycosylation (CDG) are autosomal recessive disorders of N-glycans processing. Several different subtypes have been identified in recent years. Cerebellar atrophy is a characteristic finding in subtype Ia. We report clinical, imaging and genetic findings in a patient with a particularly benign clinical course, who had a normal CT at the age of 9 months and a new, previously undescribed, combination of mutations of the PMM gene locus on chromosome 16p13 (647,691). The 691 mutation has been described only in severe cases so far. This could indicate that genotype-phenotype correlation is lower than expected.

Brain↗
PubMed2026

Phenotypic and Genetic Characterization of 64 Egyptian Children With Neuronal Ceroid Lipofuscinosis.

BACKGROUND: Neuronal ceroid lipofuscinoses (NCLs) are the most common neurodegenerative diseases in childhood. This study aimed to investigate the phenotypic and genetic spectrum of NCLs in Egypt. METHODS: This descriptive study involved children with NCLs diagnosed and managed at five Egyptian centers between 2019 and 2024. Demographic, clinical, brain imaging, and genetic data were systematically evaluated. Identified variants in NCL-related genes were classified following the American College of Medical Genetics and Genomics guidelines. RESULTS: The cohort included 64 Egyptian children (from 57 families) with eight NCL types. The most commonly identified genotype was CLN2 (17/64, 27%), followed by CLN1 and CLN7 (12/64, 19% each). Patients generally exhibited the classic manifestations of NCLs, particularly motor regression (64/64, 100%), cognitive decline (64/64, 100%), language impairment (64/64, 100%), epilepsy (57/64, 89%), and vision loss (47/64, 73%). Notably, developmental regression (12/17, 71%) was the predominant presenting symptom for CLN2. Brain imaging generally showed typical cerebral and cerebellar atrophy in 95% (61/64) and 84% (54/64) of cases, respectively. Nevertheless, thalamic abnormalities were observed in only 16% (10/64) of cases. A total of 46 distinct variants were identified across eight NCL-related genes, including 23 novel ones, with the majority (33/46, 72%) being private. There was a median diagnostic delay of 2 years, and none of the patients received specific therapy. CONCLUSIONS: This study reports the largest cohort of children with NCLs from Egypt, including 12 patients with the less-commonly reported CLN7 subtype, which expands the demographic, clinical, and molecular spectrum of these diseases.

Humans↗
PubMed1999

Amplified fragment length polymorphism (AFLP) reveals introgression in weedy Onopordum thistles: hybridization and invasion.

Onopordum L. (Compositae) is an extremely diverse genus of thistles, which includes several species that have become serious pasture weeds in several regions of the world. We present a comparison of the genetic diversity in invasive forms of Onopordum from Australia with several known native European species. A total of 108 polymorphic genetic markers was generated using amplified fragment length polymorphism (AFLP) fingerprinting. Non-metric multidimensional scaling (NMDS) revealed that Australia contained O. acanthium, O. illyricum and a full range of genetic intermediates between these species. Intermediates largely comprised segregating fragments diagnostic for European O. acanthium and O. illyricum with a low frequency of fragments that were diagnostic for other species never recorded in Australia. The current genetic patterns in Australia may be best explained by a combination of processes, both in the native and in the alien range. These include multiple introductions of seed, including hybrid material, and the continuous dispersal in Australia, leading to an increase in the contact among hybridizing taxa. Such processes appear to have produced more widespread hybridization and introgression in Australian Onopordum than is found in Europe.

DNA Fingerprinting↗
PubMed2005

Towards an understanding of unique and shared pathways in the psychopathophysiology of ADHD.

Most attention deficit hyperactivity disorder (ADHD) research has compared cases with unaffected controls. This has led to many associations, but uncertainties about their specificity to ADHD in contrast with other disorders. We present a selective review of research, comparing ADHD with other disorders in neuropsychological, neurobiological and genetic correlates. So far, a specific pathophysiological pathway has not been identified. ADHD is probably not specifically associated with executive function deficits. It is possible, but not yet established, that ADHD symptoms may be more specifically associated with motivational abnormalities, motor organization and time perception. Recent findings indicating common genetic liabilities of ADHD and other conditions raise questions about diagnostic boundaries. In future research, the delineation of the pathophysiological mechanisms of ADHD needs to match cognitive, imaging and genetic techniques to the challenge of defining more homogenous clinical groups; multi-site collaborative projects are needed.

Attention Deficit Disorder with Hyperactivity↗
PubMed1998

Noninvasive In vivo high-resolution magnetic resonance imaging of atherosclerotic lesions in genetically engineered mice.

BACKGROUND: The pathogenesis of atherosclerosis is currently being investigated in genetically engineered small animals. Methods to follow the time course of the developing pathology and/or the responses to therapy in vivo are limited. METHODS AND RESULTS: To address this problem, we developed a noninvasive MR microscopy technique to study in vivo atherosclerotic lesions (without a priori knowledge of the lesion location or lesion type) in live apolipoprotein E knockout (apoE-KO) mice. The spatial resolution was 0.0012 to 0.005 mm3. The lumen and wall of the abdominal aorta and iliac arteries were identified on all images in apoE-KO (n=8) and wild-type (n=5) mice on chow diet. Images obtained with MR were compared with corresponding cross-sectional histopathology (n=58). MR accurately determined wall area in comparison to histopathology (slope=1.0, r=0.86). In addition, atherosclerotic lesions were characterized in terms of lesion shape and type. Lesion type was graded by MR according to morphological appearance/severity and by histopathology according to the AHA classification. There was excellent agreement between MR and histopathology in grading of lesion shape and type (slope=0.97, r=0.91 for lesion shape; slope=0. 64, r=0.90 for lesion type). CONCLUSIONS: The combination of high-resolution MR microscopy and genetically engineered animals is a powerful tool to investigate serially and noninvasively the progression and regression of atherosclerotic lesions in an intact animal model and should greatly enhance basic studies of atherosclerotic disease.

Animals↗
PubMed2006

Congenital myotonic dystrophy: variability in muscle involvement and histopathological process.

In order to understand the involvement of specific muscles in congenital myotonic dystrophy type 1 (DM1), we studied the clinical manifestations, and the genetic effects on various tissues in 2 siblings with congenital DM1. The distal leg muscles were more severely involved than the thigh muscles, as seen in the skeletal muscle magnetic resonance imaging. Molecular genetic analysis of the myotonic dystrophy type 1 protein kinase showed an elongation of the CTG triplet repeats between 850 and 1400 in the leukocytes, skin, fat, tendon, and muscles. Muscle biopsies showed a significant difference in the fiber type distribution between these two congenital DM1 patients. One revealed a prominent involvement of the tibialis anterior muscle with a predominance of type 1 fibers, similar to those muscle fiber distributions in older congenital or classic DM1 patients, suggesting a neurotrophic influence during muscle development. Another revealed a predominance of type 2 fibers in all muscle specimens, and dystrophic changes were observed in the peroneus longus muscle indicating a delayed differentiation or maturation of muscle fibers. We conclude that despite nearly the same number of CTG repeats in the leukocytes, highly individual variability of muscle differentiation may occur at teenagers of congenital DM1 in addition to different pathological findings in various skeletal muscles of patients with congenital DM1.

Adolescent↗
PubMed2004

Chronic inflammatory rheumatismal diseases--paraclinical diagnosis.

The rheumatismal diseases constitute a major problem of public health, the pathology of the locomotor system representing today the main cause of invalidity in the world. The inflammatory chronic rheumatisms affect the young population, and, between the onset of the disease and diagnosis (approximately one year), the patient does not accuse major clinical complaints. In this context, the present work proposes a presentation of the main paraclinic methods and techniques, which may direct the clinician in giving a correct and early diagnosis of the main chronic inflammatory rheumatismal disorders. The paraclinic methods and techniques for assessing the intensity and evolution of the chronic rheumatismal inflammatory processes may be classified as follows: genetic, biological, histological, and imagistic. The inflammatory reaction is a nonspecific long-term reaction of the body defense systems, as response to the continuous and recurrent aggression. It is characterized by the predominance of the lymphocytes and macrophages at the level of the focus infectious and an intense process of neoangiogenesis and fibroblastic proliferation accompanies it. The paraclinic methods and techniques for assessing the intensity and evolution of the chronic rheumatismal inflammatory processes may be classified as follows: genetic, biological, histological, and imagistic.

Biopsy↗
PubMedDate not supplied

Magnetic resonance imaging of the masseter muscle: a preliminary genetic study in monozygotic and dizygotic twins.

Magnetic resonance images of the head were taken in five monozygotic and seven dizygotic twins in order to calculate bilaterally masseter muscle cross-sectional areas and total volume. Comparing correlation coefficients between cotwins, genetic influences could be expected for maximal cross-sectional area but not for volume measurements. Model fitting revealed that additive genetic factors explained 93.9% of the variance for the left and 82.4% for the right maximal masseter muscle cross-sections. It is anticipated that while the number of masseter muscle fibers is under strong genetic control, the length of individual fibers can be influenced by specific environmental factors. In the second part of the investigation, cephalometric measurements from lateral headplates were compared with these masseter muscle values in 10 twin pairs. Only three of the 15 angular and five (three vertical, one transversal, and one sagittal measurement) of the 20 linear measurements were significantly correlated with masseter muscle values.

Face↗
PubMed2005

Craniofacial syndromes.

The neonate with cranio-facial dysmorphism presents a difficult diagnostic problem as only a limited number of cranio-facial syndromes can be diagnosed with confidence in the neonatal period. This review outlines a systematic approach to this problem and discusses the genetic aspects and clinical features of the common cranio-facial syndromes that can be diagnosed in the neonatal period.

Chromosomes↗
PubMed1993

Late-onset Friedreich's ataxia. Molecular genetics, clinical neurophysiology, and magnetic resonance imaging.

OBJECTIVE--To clarify the nosological classification of late-onset Friedreich's ataxia (LOFA), ie, patients who have later onset of Friedreich's ataxia (FRDA), often after 25 years of age. DESIGN--Comparison of clinical examination data, nerve conduction studies, electronystagmographic recording, and magnetic resonance imaging of a family with LOFA with a group of patients with FRDA. Genetic linkage analysis was performed in the family with LOFA. SETTING--Referral center. PATIENTS--Thirteen patients satisfied classic diagnostic criteria of FRDA, and three patients from one family satisfied all diagnostic criteria of FRDA but with disease onset after 25 years. RESULTS--Results of nerve conduction studies, electronystagmographic recording, and magnetic resonance imaging in patients with LOFA closely corresponded to observations made in patients with FRDA. In addition, genetic linkage analysis using markers tightly linked to the FRDA locus on chromosome 9 showed that all affected members of the LOFA family, but not their unaffected siblings, had inherited identical paternal and maternal genotypes. CONCLUSIONS--Data suggest that LOFA may also result from mutation within the FRDA locus.

Adolescent↗
PubMed2003

Targeting tumours with genetically enhanced T lymphocytes.

The genetic modification of T lymphocytes is an important approach to investigating normal T-cell biology and to increasing antitumour immunity. A number of genetic strategies aim to increase the recognition of tumour antigens, enhance antitumour activities and prevent T-cell malfunction. T cells can also be engineered to increase safety, as well as to express markers that can be tracked by non-invasive imaging technologies. Genetically modified T cells are therefore proving to be of great value for basic immunology and experimental immunotherapy.

Adjuvants, Immunologic↗
PubMed2006

An in vivo technique for pharmacological manipulation of Drosophila brain during optical recording.

Drosophila melanogaster, an established model for genetic manipulation, has recently been used for studying olfactory perception, learning, and memory. Some of these important behavioral phenomena have been dissected with defined mutants, some to a single biochemical lesion, expressed in central brain structures known as the mushroom bodies. A previously introduced preparation used a window in the head capsule through which these structures could be imaged using genetically expressed fluorescent calcium sensors while applying physiological odorant stimuli. Unfortunately, technical constraints prevented direct manipulation of the mushroom bodies with this preparation. I describe here a preparation that will allow, for the first time, the direct pharmacological manipulation of these important structures during imaging in the living adult fly. Responses to discreet applications of acetylcholine were reversibly blocked with tubocurare and reversibly eliminated in calcium-free Ringers. This new technique will significantly enhance the usefulness of the Drosophila model system, allowing a more quantitative examination of the mechanisms involved in olfactory learning and memory.

Acetylcholine↗
PubMed2002

Low-grade gliomas in adults.

PURPOSE OF REVIEW: This paper aims to summarize the current thinking about the management of adult supratentorial low-grade gliomas. These are well differentiated primary brain tumours that typically develop in young adults. Their biological behaviour is poorly understood but the majority of these tumours grow slowly, infiltrate surrounding normal brain, and show an intrinsic tendency to undergo malignant transformation to high-grade gliomas. Surgery and radiotherapy are the main treatment options, but their precise role and timing are controversial. RECENT FINDINGS: Resective surgery is at best regarded as a practice option because there is a paucity of good quality evidence to show that extent of resection correlates with survival. Radiotherapy prolongs progression-free survival but not overall survival and may lead to long-term cognitive deficits, although not as widespread as had previously been thought. A minority of tumours with oligodendroglial differentiation are chemosensitive and this correlates with allelic loss of chromosomes 1p and 19q. New imaging and molecular techniques, in particular gene microarray studies, are providing more information about these tumours, although they have yet to have a significant impact on clinical management. SUMMARY: The best management of low-grade gliomas is still unknown but advances in molecular genetics and imaging are improving our ability to prognosticate and follow the natural history of these tumours.

Disease-Free Survival↗
PubMed1998

Attention deficit hyperactivity disorder: advances in cognitive, neurobiological, and genetic research.

Conceptual and technological advances in cognitive neuroscience and molecular genetics have the potential to identify the pathogenesis of psychiatric disorders. This article reviews the application of these technologies to the scientific study of attention deficit hyperactivity disorder. It begins with a summary of shifts in conceptualization and scientific study of this common condition. This is followed by a critical review of findings from recent cognitive, neuroimaging, and genetic studies. The available data do not yet permit an integration across these different levels of enquiry, but implicate problems in response inhibition, dysfunction of frontostriatal networks, and genetic factors in the pathogenesis of this complex behavioral phenotype. The review closes with suggestions for future interdisciplinary research.

Attention Deficit Disorder with Hyperactivity↗
PubMed2004

In vivo imaging of neuronal activity by targeted expression of a genetically encoded probe in the mouse.

Genetically encoded probes show great promise in permitting functional imaging of specified neuronal populations in the intact nervous system, yet their in vivo application has been limited. Here, we have targeted expression of synapto-pHluorin, a pH-sensitive protein that reports synaptic vesicle fusion, to olfactory sensory neurons in mouse. Synapto-pHluorin selectively labeled presynaptic terminals of sensory neurons in glomeruli of the olfactory bulb. Odorant stimulation evoked large-amplitude fluorescence increases that were localized to individual glomeruli in vivo, correlated with presynaptic calcium influx, graded with stimulus intensity, and stable over a period of days. Spatial patterns of odorant-activated glomeruli were distributed and did not change systematically with increasing carbon chain length, in contrast to the finely organized chemotopy that has been reported using other imaging methods. Targeted expression of synapto-pHluorin in mouse will permit the analysis of previously inaccessible neuronal populations and chronic imaging from genetically identified neurons in vivo.

Aldehydes↗