Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “imaging genetics”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 199 records · Page 11Linked to original sources
PubMed2006

Mitochondrial dysfunction and migraine: evidence and hypotheses.

The molecular basis of migraine is still not completely understood. An impairment of mitochondrial oxidative metabolism might play a role in the pathophysiology of this disease, by influencing neuronal information processing. Biochemical assays of platelets and muscle biopsies performed in migraine sufferers have shown a decreased activity of the respiratory chain enzymes. Studies with phosphorus magnetic resonance spectroscopy ((31)P-MRS) have demonstrated an impairment of the brain oxidative energy metabolism both during and between migraine attacks. However, molecular genetic studies have not detected specific mitochondrial DNA (mtDNA) mutations in patients with migraine, although other studies suggest that particular genetic markers (i.e. neutral polymorphisms or secondary mtDNA mutations) might be present in some migraine sufferers. Further studies are still needed to clarify if migraine is associated with unidentified mutations on the mtDNA or on nuclear genes that code mitochondrial proteins. In this paper, we review morphological, biochemical, imaging and genetic studies which bear on the hypothesis that migraine may be related to mitochondrial dysfunction at least in some individuals.

Animals↗
PubMed1997

Expression of apo-aequorin during embryonic development; how much is needed for calcium imaging?

Aequorin is a bioluminescent calcium indicator consisting of a 21 kDa protein (apo-aequorin) that is covalently linked to a lipophilic cofactor (coelenterazine). The aequorin gene can be expressed in a variety of cell lines and tissues, allowing non-invasive calcium imaging of specific cell types. In the present paper, we describe the possibilities and limitations of calcium imaging with genetically introduced apo-aequorin during embryonic development. By injecting aequorin into sea urchin, Drosophila and zebrafish eggs, we found that higher aequorin concentrations are needed in smaller eggs. Our results suggest that for measuring resting levels of free cytosolic calcium, one needs aequorin concentrations of at least 40 microM in sea urchin eggs, 2 microM in Drosophila eggs, and only 0.11 microM in zebrafish eggs. A simple assay was used to determine the absolute concentrations of expressed apo-aequorin and the percentage of aequorin formation in vivo. The use of this assay is illustrated by expression of the aequorin gene in Drosophila oocytes. These oocytes form up to 1 microM apo-aequorin. In our hands, only 0.3% of this apo-aequorin combined with coelenterazine entering from the medium to form aequorin, which was not enough for calcium imaging of the oocytes, but did allow in vivo imaging of the ovaries. From these studies, we conclude that coelenterazine entry into the cell is the rate limiting step in aequorin formation. Based on the rate of coelenterazine uptake in Drosophila, we estimate that complete conversion of 1 microM apo-aequorin would take 50 days in zebrafish eggs, 2 days [corrected] in Drosophila eggs, 7 days in sea urchin eggs or 18 h in a 10 microm tissue culture cell. Our results suggest that work based on genetically introduced apo-aequorin will be most successful when large amounts of small cells can be incubated in coelenterazine. During embryonic development this would involve introducing coelenterazine into the circulatory system of late stage embryos. Calcium imaging in early stage embryos may be best done by injecting aequorin, which circumvents the slow process of coelenterazine entry.

Aequorin↗
PubMedDate not supplied

[Cystic kidney disease in the adult. Update].

Genetic changes on the extracellular matrix of nephron basal lamina seem to underlie the pathogenesis of renal cystic disease, as also confirmed by experimental results. The cysts behave as dynamic structures and repeat some physiological features of the nephron segment which gave origin to them. These properties reflect, for instance, on the pharmacokinetics of antibacterial drugs. New imaging techniques detect more and more asymptomatic cystic formations of very little volume. Moreover, a better definition of some complications, such as haemorrhage and infections, is afforded by the RX- and RM-CT and the use of specific radiopharmaceuticals (67Ga-citrate, 99mTc-sulfur-colloids, 111In-labeled leucocytes).

Adult↗
PubMed2006

Diagnostic issues in dementia: neuroimaging as a surrogate marker of disease.

Structural neuroimaging is a routine component of the diagnostic evaluation of dementia that is used to rule out potential causes of mental impairment, whereas functional imaging can differentiate different forms of dementia. Neuroimaging also offers promise as a surrogate marker for clinical trials, and new technologies have been developed to provide measures of amyloid plaques and neurofibrillary tangles, the neuropathological hallmarks of Alzheimer's disease. Combining imaging with genetic risk data will likely improve diagnostic accuracy. These new findings warrant reconsideration of current guidelines on the use of neuroimaging in diagnosis and research in dementia.

Aged↗
PubMed2026

Mapping Focal and Generalized Effects of Common Genetic Variants on Human Brain Structure.

Genome-wide association studies (GWAS) have advanced the quest to understand how specific genetic variants influence human brain structure and function. Recent work has identified hundreds of common variants associated with subcortical brain volumes, sparking interest in how these genetic markers overlap across brain networks. While this can be estimated by hierarchical clustering of the genetic correlation matrix to identify modular patterns of shared architecture, no brain-wide maps of these effects are available. To address this, we computed polygenic scores (PGS) from loci associated with ten brain volume regions of interest (ROIs): nine major subcortical structures and intracranial volume, with each locus weighted by its association with regional volume. In an independent sample from the discovery GWAS, we performed large-scale segmentation of 3D volumetric T1-weighted MRI scans using voxel-based morphometry (VBM) to map 3D profile of regions where gray matter volume (GMV) was associated with each PGS. We found statistically significant, localized effects for PGS defined for the amygdala, thalamus, and basal ganglia, but PGS for brainstem volume was associated with widespread differences throughout the brain. These brain-wide maps reveal patterns consistent with both localized and distributed genetic influences, offering a novel approach to interpret the genomic architecture of brain structure.

GWAS↗
PubMed1998

The genetics of Parkinson's disease and parkinsonian syndromes.

The finding of a mutation in the alpha-synuclein gene in a rare autosomal dominant form of idiopathic Parkinson's disease (IPD), has prompted increased interest in identifying genes that account for the more common sporadic form. A number of association studies have suggested that functional polymorphisms in genes that play a role in dopamine, drug and toxin metabolism may increase the relative risk of IPD. Unfortunately, patient numbers are often small, and the results have not been consistently reproduced. This article reviews the evidence from epidemiological, imaging and genetic studies to determine the role of genetic susceptibility in IPD and parkinsonian syndromes.

England↗
PubMed2001

MRI phenotype is associated with response to doxorubicin and cyclophosphamide neoadjuvant chemotherapy in stage III breast cancer.

BACKGROUND: The preferred management for women with stage II or locally advanced breast cancer (LABC) is neoadjuvant chemotherapy. Pathologic response to chemotherapy has been shown to be an excellent predictor of outcome. Surrogates that can predict pathologic response and outcome will fuel future changes in management. Magnetic resonance imaging (MRI) demonstrates that patients with LABC have distinct tumor patterns. We investigated whether or not these patterns predict response to therapy. METHODS: Thirty-three women who received neoadjuvant doxorubicin and cyclophosphamide chemotherapy for 4 cycles and serial breast MRI scans before and after therapy were evaluated for this study. Response to therapy was measured by change in the longest diameter on the MRI. RESULTS: Five distinct imaging patterns were identified: circumscribed mass, nodular tissue infiltration diffuse tissue infiltration, patchy enhancement, and septal spread. The likelihood of a partial or complete response as measured by change in longest diameter was 77%, 37.5%, 20%, and 25%, respectively. CONCLUSIONS: MRI affords three-dimensional characterization of tumors and has revealed distinct patterns of tumor presentation that predict response. A multisite trial is being planned to combine imaging and genetic information in an effort to better understand and predict response and, ultimately, to tailor therapy and direct the use of novel agents.

Adult↗
PubMed1996

[Congenital muscular dystrophy with merosin deficiency: clinical, histopathological, immunocytochemical and genetic analysis].

A selective deficiency of a specific laminin isovariant, merosin made of M, B1 and B2 chains, was found in a series of 17 patients affected with congenital muscular dystrophy (CMD). The merosin deficiency was complete in 15 cases, and almost complete in two cases. An overexpression of the laminin A chain was seen in these biopsies, while B1 and B2 chains were normally expressed. Comparison of the clinical data with a series of 18 "merosin-non deficient" cases showed that the "merosin-deficient" cases were forming a more homogenous group than the "non-deficient" one. Hypotonia, contractures, motor development delay were generally more severe in the "merosin-deficient" series of cases. Moreover, white matter alterations were seen in most cases explored by MRI or scan imaging. A genetic linkage with a 6q2 locus, corresponding to the M chain gene localization, was found in a panel of informative families from French and Turkish origin with "merosin deficient" CMD. "Merosin non-deficient" families did not map on this locus. So, the "merosin-deficient" CMD can be considered as a peculiar entity within the group of Congenital Muscular Dystrophies.

Biopsy↗
PubMed1998

Pathophysiology in endothelin-1 transgenic mice.

Transgenic mice expressing the human endothelin-1 (ET-1) were generated. These mice develop glomerulosclerosis, interstitial fibrosis, and renal cysts but not hypertension. Consequently, a progressive decrease in renal blood flow and/or glomerular filtration rate was observed, demonstrated by altered creatinine clearance and by magnetic resonance imaging. These genetically altered transgenic mice provide an interesting animal model in which to elucidate the role of ET-1 in the modulation of renal hemodynamics and glomerular and tubule functions.

Animals↗
PubMed2004

Gene expression imaging with radiolabeled peptides.

An approach to image radiolabeled peptide localization at tumor sites by inducing tumor cells to synthesize membrane expressed human somatostatin receptor subtype 2 (hSSTr2) with a high affinity for radiolabeled somatostatin analogues is described. The use of gene transfer technology to induce expression of high affinity membrane hSSTr2 can enhance the specificity and degree of radiolabeled peptide localization in tumors. Employing this strategy, induction of high levels of hSSTr2 expression with selective tumor uptake of radiolabeled peptides was achieved in both subcutaneous non-small cell lung cancer and intraperitoneal ovarian cancer mouse human tumor xenograft models. The features of this genetic transduction imaging approach are: (1) constitutive expression of a tumor-associated receptor is not required; (2) tumor cells are altered to express a new target receptor or increased quantities of a constitutive receptor at levels which may significantly increase tumor targeting of radiolabeled peptides compared to uptake in normal tissues; (3) gene transfer can be accomplished by local or regional injection of adenoviral vectors; (4) it is feasible to target adenovirus vectors to tumor cells by modifying adenoviral tropism (binding) or by the use of tumor-specific promoters such that the hSSTr2 will be specifically expressed in the desired tumor; and (5) this technique can be used to image expression of a second therapeutic gene.

Animals↗
PubMed1986

Heterogeneity of lethals in a "simple" lethal complementation group.

Of 24 ethyl methanesulphonate-induced, recessive-lethal mutations in the region 9E1-9F13 of the X chromosome of Drosophila melanogaster, eight fall into a typically homogeneous lethal complementation group associated with the raspberry (ras) locus. Mutations in this group have previously been shown to be pleiotropic, affecting not only ras but also two other genetic entities, gua 1 and pur 1, which yield auxotrophic mutations.--The eight new mutations have been characterized phenotypically in double heterozygotes with gua 1, pur 1 and ras mutations. Despite their homogeneity in lethal complementation tests, the mutations prove quite diverse. For example, two mutations have little or no effect on eye color in double heterozygotes with ras2. The differences between the lethals are allele-specific and cannot be explained as a trivial outcome of a hypomorphic series.--Taken alone, the lethal complementation studies mask the complexity of the locus and the diversity of its recessive lethal alleles. By extension, we argue that the general use of lethal saturation studies provides an unduly simplified image of genetic organization. We suggest that the reason why recessive lethal mutations rarely present complex complementation patterns is that complex loci tend to produce mutations that affect several subfunctions.

Animals↗
PubMed2025

Genetic analysis of four cases of Poirier Bienvenu neurodevelopmental syndrome associated with CSNK2B variant.

BACKGROUND: CSNK2B deficiency underlies the pathogenesis of Poirier-Bienvenu neurodevelopmental syndrome (POBINDS). In this study, we present four cases of pediatric seizures caused by de novo variants in CSNK2B, with the aim to reinforce the clinical and variant data pertaining to early genetic factors associated with epilepsy. METHODS: Trio whole exome sequencing were used to detect variants in the proband and her family members, and bioinformatics annotation was performed for the variant. Sanger sequencing and CSNK2B cDNA sequencing were employed to ascertain the carrier status of additional family members and evaluate the potential impact of variants on splicing. RESULTS: All four cases presented with epilepsy as the initial manifestation, accompanied by global developmental delay, particularly in language and motor developmental delay. Cases 1, 3 and 4 exhibited full-scale tonic-clonic seizures, while case 2 displayed myoclonic and typical absence seizures. Furthermore, case 2 demonstrated delayed growth and development compared to age-matched peers. No abnormality was detected in the head magnetic resonance imaging (MRI). Genetic analysis revealed novel heterozygous variants in the CSNK2B gene in all four cases, including c.175 + 1G > A, c.73-2A > G, c.291 + 1G > A and c.481delA. In case 2, reverse transcription analysis of CSNK2B mRNA revealed the retention of the 3' end sequence of Intron 2 and deletion of the 5' end sequence of Exon 3. In treatment, four case received a combination of one to three types of antiseizure medication and rehabilitation training individually. Case 1 continued to experience seizures to varying degrees, while cases 2-4 demonstrated effective seizure control. Overall motor and intellectual development improved in all four cases, however, there was slow recovery in language function. CONCLUSION: This study elucidates the molecular etiology of epilepsy in four cases with POBINDS and expands the mutational spectrum of pathogenic variants in the CSNK2B, highlighting their impact on splicing. The highly genetic heterogeneous phenotype of POBINDS relies on the detection of pathogenic variants in CSNK2B. Conventional antiseizure medication effectively control seizures, while rehabilitation treatment can significantly improve intelligence and motor function to varying degrees; however, language recovery tends to be relatively slow.

Humans↗
PubMed2003

MR imaging of hepatocellular carcinoma arising in genetic hemochromatosis.

A case of a 51-year-old male with previously unsuspected genetic hemochromatosis (GH) associated with hepatocellular carcinoma (HCC), for which MR imaging was useful in diagnosis, is presented. Contrast-enhanced ultrasonography depicted a mass in segment 8 of the liver and a liver tumor was suspected. The mass could not be revealed on unenhanced or enhanced CT examination. MR imaging with unenhanced T1-weighted FLASH and T2-weighted gradient echo sequences clearly depicted the tumor; the tumor appeared hyperintense against a background of low hepatic signal intensity caused by iron overload. The iron-overloaded liver provided a natural source of paramagnetic contrast for detection of HCC. Studies are required to further assess the accuracy of these sequences in detection of HCC in patients with GH.

Carcinoma, Hepatocellular↗
PubMed2001

Current investigations in autism brain tissue research.

Brain tissue research has developed into a high-tech, multifaceted approach to understanding neurological disorders. Directed toward autism spectrum disorders, this investigative approach combines with other disciplines, such as imaging and genetics, to help explain the range and intensity of behaviors that characterize these disorders. This report is intended as an update on current autism brain research efforts and has a dual purpose: first, to disseminate information to the scientific community in the hope of stimulating more thinking about autism research and future collaborations; and second, to let the autism community know what is happening with this precious resource that was donated in the hope of determining the cause of autism and finding effective treatments.

Autistic Disorder↗
PubMed2006

Fragile X premutation with atypical symptoms at onset.

OBJECTIVE: To evaluate the presence of carriers of the fragile X premutation among male patients with sporadic ataxia without expansion into known spinocerebellar ataxia genes. DESIGN: Clinical and genetic examinations were performed on patients with sporadic pure ataxia and patients with ataxia associated with extracerebellar features such as pyramidal and extrapyramidal signs, dementia, or peripheral neuropathy. SETTING: University department of neurology. PATIENTS: One hundred forty-two Italian men with sporadic ataxia with onset at age 30 to 84 years. INTERVENTIONS: The CGG repeat size of the FMR1 gene was evaluated with fluorescent polymerase chain reaction. Premutated allele lengths were confirmed with Southern blot analysis. RESULTS: FMR1 premutation alleles with a repeat number greater than 55 were detected in 3 probands (2.1%) from a total of 142 male subjects initially referred to our university medical center for evaluation of sporadic ataxia. Two patients had typical fragile X syndrome with associated tremor or ataxia, and the third patient had spastic paraparesis without clear symptoms of cerebellar ataxia and without the common signs seen at magnetic resonance imaging. CONCLUSIONS: Genetic analysis of the FMR1 gene could provide a reliable diagnostic tool for the definitive diagnosis of late-onset ataxias. Additional studies are needed to clarify the importance of premutation screening in patients with movement disorders or other associated atypical features at onset, such as paraparesis.

Adult↗
PubMed1998

Automatic construction of eigenshape models by direct optimization.

A new approach to the problem of automatic construction of eigenshape models is presented. Eigenshape models have proved to be successful in a variety of medical image analysis problems. However, automatic construction of eigenshape models has proved to be a difficult problem, and in many applications the models are built by hand-a painstaking process. We show that the fundamental problem is a choice of the correct pose and parametrization of each shape in the training set. Eigenshape models are not invariant under reparametrizations and pose transformations of the training shapes. Since there is no a priori correct choice for the pose and parametrization of each shape, their value should be chosen so as to produce a model that is compact and specific. This problem can be solved by finding an objective function that measures these properties and varying the pose and parametrization of each shape to optimize this function. We show that the appropriate objective function is the determinant of the covariance matrix. We go on to show how this objective function can be optimized by a genetic algorithm (GA) and thus give a practical method for building eigenshape models. The models produced are often better than hand-built ones. The advantages of a GA over other choices of optimization method are that no assumptions about the nature of the shapes being modelled is required and that the global minimum of the objective function can, in principle, be found.

Algorithms↗
PubMedDate not supplied

MR imaging of Kallmann syndrome, a genetic disorder of neuronal migration affecting the olfactory and genital systems.

PURPOSE: We report the MR findings in nine patients with clinical and laboratory evidence of Kallmann syndrome (KS), a genetic disorder of olfactory and gonadal development. In patients with KS, cells that normally express luteinizing hormone-releasing hormone fail to migrate from the medial olfactory placode along the terminalis nerves into the forebrain. In addition, failed neuronal migration from the lateral olfactory placode along the olfactory fila to the forebrain results in aplasia or hypoplasia of the olfactory bulbs and tracts. Patients with KS, therefore, suffer both reproductive and olfactory dysfunction. METHODS: Nine patients with KS underwent direct coronal MR of their olfactory regions in order to assess the olfactory sulci, bulbs, and tracts. A 10th patient had MR findings of KS, although the diagnosis is not yet confirmed by laboratory tests. RESULTS: Abnormalities of the olfactory system were identified in all patients. In particular, the anterior portions of the olfactory sulci were uniformly hypoplastic. The olfactory bulbs and tracts appeared hypoplastic or aplastic in all patients in whom the bulb/tract region was satisfactorily imaged. In two (possibly three) patients, prominent soft tissue in the region of the bulbs suggests radiographic evidence of neurons that have been arrested before migration. CONCLUSIONS: Previous investigators of patients with KS used axial MR images to demonstrate hypoplasia of the olfactory sulci but offered no assessment of the olfactory bulbs. In the present study we used coronal images to show hypoplasia of both olfactory sulci and bulbs. In addition, we found what we believe to be the radiologic correlate of arrested neuronal migration in KS.

Adolescent↗