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.

SourceResearch connectionFrom yearThrough year

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

At least 325 records · Page 18Linked to original sources

PubMed2004

Autosomal recessive spinocerebellar ataxia and peripheral neuropathy with raised alpha-fetoprotein.

We describe three patients from two families with progressive spinocerebellar ataxia, peripheral neuropathy, raised alpha-fetoprotein (AFP) and hypercholesterolaemia. Two siblings had identical clinical features, with late childhood onset of symptoms and slow progression, requiring crutches to walk at ages 37 and 38 years. Another patient developed ataxia aged 13 years and became wheel-chair bound by 20 years of age. Although they all had raised serum AFP levels, their clinical, immunological, biochemical, cytogenetic and molecular genetic studies failed to support a diagnosis of Ataxia Telangiectasia. Extensive investigation including imaging, biochemical and genetic studies excluded other known ataxias. Their clinical features most closely resemble the phenotype of a single consanguineous Japanese family with four individuals affected by spinocerebellar ataxia, peripheral neuropathy, raised AFP and hypercholesterolaemia. Homozygosity mapping has identified a locus in this Japanese family at 9q34. Haplotype analysis of our cases demonstrated possible linkage to 9q34, suggesting these may be the first Caucasian families described with this disorder.

Adult↗

PubMed2006

Dual-color-coded imaging of viable circulating prostate carcinoma cells reveals genetic exchange between tumor cells in vivo, contributing to highly metastatic phenotypes.

Color-coded imaging analysis revealed yellow fluorescent metastasis precursor cells that were readily recognized in the blood of tumor-bearing mice after mixtures of red fluorescent protein (RFP)- and green fluorescent protein (GFP)-expressing PC-3 human prostate carcinoma cells were implanted in the nude mouse prostate and metastasized. The yellow fluorescent cells were purified from the blood of nude mice to 99% homogeneity by FACS, expanded in culture, and reimplanted in the prostate of nude mice. The yellow fluorescent phenotype was heritable and stably maintained by tumor cells for many generations in vitro and in vivo. In the animals implanted with the yellow-fluorescing cells, 100% developed aggressive metastatic cancer. Lung metastases were demonstrated in 100% of the animals as early as four weeks after injection of the yellow-fluorescing cells in the mouse prostate. In contrast, when the GFP- and RFP-expressing parental cells were inoculated into the mouse prostate separately, none of the animals developed lung metastasis. All animals had almost exclusively yellow fluorescent cells in the blood and bone marrow. These results are consistent with the idea that spontaneous genetic exchange between tumor cells in vivo contributes to genomic instability and creation of highly metastatic cells.

Animals↗

PubMed2003

Developing culturally sensitive cancer genetics communication aids for African Americans.

The goal of this project was to develop educational materials to communicate genetic health information in a culturally sensitive manner. These materials were designed to communicate information about cancer risk, genetic testing options, and health management options in an African American kindred with a known BRCA1 mutation. Educational materials were pilot-tested in four African American focus groups varying in socioeconomic status and gender. The audiotaped focus groups consisted of presentation of the educational materials, followed by a feedback session led by an African American facilitator. Qualitative analysis of the focus group transcripts identified important themes and the educational materials were revised in response to the participants' suggestions. The products included a booklet and a flip chart for use in educational sessions. Focus group participants recommended a substantial reduction in technical detail, and recommended that information be personalized and made relevant to the lives of the target population. Other critical themes included the importance of building trust in the medical system and avoiding words and images that have strong negative associations in the African American community. Strategies that were successful included nontechnical images to explain genetic concepts, clip art images to energize and personalize word slides, vibrant color, identifiably African American figures, and the development of themes relevant to many African Americans. The use of these materials in an ongoing study offering BRCA1 counseling and testing to a large, rural Louisiana-based kindred will provide additional feedback about the effectiveness of the culturally tailored genetic education and counseling materials.

Adult↗

PubMed2004

Functional brain mapping of extraversion and neuroticism: learning from individual differences in emotion processing.

This review outlines how functional brain imaging, using an individual-differences approach in the processing of emotional stimuli, has begun to reveal the neural basis of extraversion (E) and neuroticism (N), two traits that are linked to both emotion and health. Studies using functional magnetic resonance imaging have shown that individual differences in participants' E and N scores are correlated with individual differences in brain activation in specific brain regions that are engaged during cognitive-affective tasks. Imaging studies using genotyped participants have begun to address the molecular mechanisms that may underlie these individual differences. The multidisciplinary integration of brain imaging and molecular genetic methods offers an exciting and novel approach for investigators who seek to uncover the biological mechanisms by which personality and health are interrelated.

Amygdala↗

PubMed2001

Update on genetic disorders affecting white matter.

The classification of diseases affecting white matter has changed dramatically with the use of magnetic resonance imaging. Classical leukodystrophies, such as metachromatic leukodystrophy and Krabbe's disease, account for only a small number of inherited diseases that affect white matter. Magnetic resonance imaging has clarified genetic disorders that result in white matter changes or leukoencephalopathies. The term leukoencephalopathy is used to reflect the broader number of diseases that may cause as either primary or secondary changes in myelin development. This review attempts to categorize white matter disorders into classes such as lipid, myelin protein, organic acids, and defects in energy metabolism, in addition to other causes.

Brain↗

PubMedDate not supplied

[Incidence of genetic alterations in spontaneous abortion. Attempted correlations with beta-HCG values and with the ultrasonic image].

BACKGROUND AND AIMS: The percentage of genetic alterations in spontaneous abortions reported in the literature is between 54% and 76%. The authors felt it was interesting to analyse the frequency of genetic alterations in spontaneous abortions and to establish the correlation between the karyotype and other available data at the time of clinical observation: Beta-HCG values, ultrasonographic imaging, patient's age, parity, week of pregnancy. METHODS: One hundred and twenty samples of trophoblastic tissue taken from spontaneous abortions underwent karyotype analysis. The authors report the correlations between genetic findings and patient age, parity, beta-HCG values, ultrasonographic images and the week of pregnancy. RESULTS: Sixty-two chromosomic anomalies (51.67%) were observed; the other 58 samples (48.33%) were normal. The correlations between chromosome anomalies and the parameters analysed are reported in the other tables and figures. CONCLUSIONS: Neither the ultrasonographic images nor beta-HCG values appear to identify genetic etiology as the cause of spontaneous abortion; this is also true in relation to the week of pregnancy and maternal age. Parity appears to be the sole exception: in this population, spontaneous abortions with a genetic etiology were more frequent in primagravidas compared to other patients. This confirms the fact that hereditary genetic anomalies tend to become evident right from the start of a couple's obstetic history.

Abortion, Habitual↗

PubMed2003

Potential biological markers for cerebrovascular disease.

Cerebrovascular diseases can causes cognitive impairment and dementia by loss of neurons and synaptic connections, destruction of axons, and demyelinization. Biological markers including genetic tests, brain imaging techniques, and biochemical assays in the CSF are valuable for the identification and quantification of cerebrovascular diseases. Genetic tests may be used to detect mutations that cause hereditary cerebral amyloid angiopathies or cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Structural CT and MR imaging is routinely used to visualize and quantify infarcts and white-matter changes. Functional SPET and PET imaging can demonstrate focal and remote effects of vascular lesions on cerebral blood flow and metabolism. Biochemical imaging using proton MRS is a nonspecific marker for neuronal and axonal damage. Among biochemical markers in the CSF, tau protein, phospho-tau, and beta amyloid protein are helpful to differentiate vascular dementia from Alzheimer's disease.

Aged↗

PubMed2005

Evidence for white matter abnormalities in schizophrenia.

PURPOSE OF REVIEW: The purpose of this review is to highlight important recent imaging, histological, and genetic findings relevant to white matter abnormalities in schizophrenia. It is cast within the context of research findings conducted over the last 5 years, where we analyze their importance in understanding schizophrenia, as well as discuss future directions for research. RECENT FINDINGS: White matter abnormalities have long been hypothesized in schizophrenia, although only recently has it become possible to investigate them more closely. This has come about as a result of advances in neuroimaging, including new imaging techniques sensitive to white matter structure, as well as advances in computer science, with new analysis techniques making it possible to evaluate several interconnected brain regions at a time. Postmortem studies, with advances such as fluoroscopy and electron microscopy, have also led to quantifying populations of different brain cells, including myelin-forming oligodendrocytes. Moreover, molecular studies enable examination of immunoreactivity of proteins that are responsible for building myelin sheaths. Additionally, microarray genetic studies allow us to investigate myelin-related genes in schizophrenia. Taken together, these technological advances bring us closer to understanding white matter pathology in schizophrenia. SUMMARY: Advances in new imaging techniques likely account for the renewed interest in investigating white matter abnormalities in schizophrenia, with over 30 new articles published on this topic in the last 12 months, compared with 11 the year before. We review recent imaging, histological, and genetic findings that suggest white matter abnormalities in schizophrenia.

Journal Article↗

PubMed2001

Salmonella-based tumor-targeted cancer therapy: tumor amplified protein expression therapy (TAPET) for diagnostic imaging.

In preclinical studies, genetically engineered Salmonella have the ability to localize, selectively accumulate, and persist within transplantable murine tumors, spontaneous murine tumors and human tumor xenographs, and can express therapeutic proteins at high levels. These strains of engineered non-virulent Salmonella typhimurium display the capacity to accumulate and grow selectively in a variety of tumor types and to inhibit the growth of primary and metastatic tumors following intravenous injection into tumor-bearing mice. One strain of the bacteria (VNP20009) which has endogenous antitumor activity is currently in Phase I clinical trials. The bacteria are highly attenuated and genetically stable. The combination of the lipid mutation and the purine auxotrophy attenuate the virulence of the bacteria by greater than 10000-fold and enhance the specificity of the bacteria for tumor tissue. These bacteria have been found to be safe in mice, pigs and monkeys when administered intravenously. Second-generation Salmonella vectors will be developed to include transgenes that will express therapeutic agents and reporter transgenes for non-invasive imaging. We have performed a preliminary study to demonstrate localization of [(14)C]FIAU in tumored mice pretreated with Salmonella expressing HSV1-TK. The [(14)C]FIAU radioactivity and bacterial count data strongly support a Salmonella(TK)-dependent [(14)C]FIAU accumulation of at least 30-fold higher in tumor tissue compared to muscle tissue. These data warrant further investigation on the use of genetically engineered Salmonella as a systemically administered tumor-specific agents for tumor therapy and delivery of diagnostic imaging markers.

Animals↗

PubMed1992

Magnetic resonance imaging and assessment of liver iron content in genetic hemochromatosis.

Computed tomography (CT) scanning is not highly sensitive in the assessment of liver iron content and magnetic resonance imaging (MRI) appears to be more efficient. The aim of this study was to determine the effectiveness of MRI in the evaluation of liver iron content using a standard spin-echo technique. The study included 23 patients with genetic hemochromatosis and 24 non-iron-overloaded patients as controls. A comparison was made of: (a) MRI signal intensity of liver, spleen, paravertebral muscles and subcutaneous adipose tissue using two different spin-echo sequences (SE 500/28; SE 2000/28,56); (b) liver attenuation determined by a single energy CT scan; and (c) a biochemical determination of hepatic iron. There was a significant decrease in liver signal intensity in the genetic hemochromatosis group (256 +/- 201, mean +/- S.D.) compared with the control group (801 +/- 413, p less than 0.001), but there was no correlation with liver iron concentration. However, such a correlation was found and was even more highly significant than in CT when the ratio between the liver and another organ was taken into account. For a lower limit of liver/spleen ratio calculated at 0.46 (mean 2 S.D. in the control group), the specificity (0.96) of MRI was satisfactory, but the sensitivity (0.78) remained insufficient (MRI being unable to detect an iron overload of up to 125 mumol/g). Hopefully, these results might be improved in the near future by using more sensitive sequences such as gradient echo sequences.

Adipose Tissue↗

PubMed2004

MR imaging and spectroscopy in juvenile Huntington disease.

Juvenile Huntington disease manifests differently from adult Huntington disease and has more variability in presentation. We describe a child with cognitive decline and adventitial movements in whom Huntington disease was confirmed with genetic testing. MR imaging showed abnormal T2 prolongation in the putamina and progressive caudate atrophy, and MR spectroscopy revealed elevated myoinositol and diminished N-acetyl aspartate, creatine, and phosphocreatine. Imaging findings of caudate atrophy and abnormal T2 prolongation in the putamina with MR spectroscopy findings consistent with dense gliosis can be helpful indicators of juvenile Huntington disease.

Aspartic Acid↗

PubMed2002

MR imaging of iron depositional disease.

This article discusses the physiology of iron metabolism in humans. The pathophysiology and MR imaging findings of disorders that result in iron deposition in the liver are described. Emphasis is placed on genetic, clinical, and imaging findings of hemochromatosis. Radiologists should familiarize themselves with the patterns of iron deposition on MR images in order to suggest a potential etiology, which may not be known at the time of imaging.

Hemochromatosis↗

PubMed2000

First experiences in screening women at high risk for breast cancer with MR imaging.

Women with a genetic predisposition for breast cancer are often advised surveillance with physical examination twice a year and mammography once a year from 25 years onwards. However, the sensitivity of the mammography decreases when breast tissue is dense and this is seen in 40-50% of women under 50 years. We therefore investigated whether magnetic resonance imaging (MRI) in addition to the normal surveillance could detect cancers otherwise missed. In 109 women with over 25% risk of breast cancer, MRI was performed because over 50% dense breast tissue was seen at mammography and no suspect lesion was seen at the previous screening. MRI detected breast cancers in three patients (2.8%) occult at mammography and with no new palpable tumor, twice at stage T1bN0 and T1cN0 once. Two cancers were expected. MRI was false positive in six women, resulting in two benign local excisions because ultrasound or fine needle examination confirmed suspicion. We had no false negative MRI results. MRI proved true benign in four BRCA 1/2 gene mutation carriers at histologic examination. Preoperative wire localization of the malignancies detected at MRI proved necessary as the tumor was not palpable in the lumpectomy specimen nor visible at specimen radiology. The extra cost of breast MRI in addition to mammography and physical examination was [symbol: see text]uro13.930 per detected cancer. The cost of the detection of one breast cancer patient in our national screening program is [symbol: see text]uro9000. During follow-up of patients with a familial risk in whom the first breast cancer was detected at MRI, MRI detected two recurrent cancers in stage T1bN0 and T1cN0 and one contralateral cancer T1aNo. Breast MRI is promising in screening young women at high risk for breast cancer, as it can advance the detection of cancers still occult at mammography and physical examination; but the cost may be considerable.

Adult↗

PubMed1999

Regional differences in genetic subgroup frequency in hereditary cerebellar ataxia, and a morphometrical study of brain MR images in SCA1, MJD and SCA6.

Molecular genetic assessments of 69 individuals in 44 families with hereditary cerebellar ataxia (HCA) were made to determine the relative frequencies of subtypes of HCA in Yamagata, Japan. Fifteen families (34%) had SCA1, none had SCA2, nine (20%) had MJD, five (11%) had SCA6 and nine (20%) had DRPLA. These findings differ markedly from those in other regions of Japan and the rest of the world. A morphometrical study of the brain MR images also was made on 38 individuals with SCA1 (n = 14), MJD (n = 8) or SCA6 (n = 16). In SCA1, the ventral pons was atrophic in proportion to the amount of cerebellar atrophy. In MJD, both the pons and the cerebellum were atrophic, cerebellar atrophy being less pronounced than that in SCA1 and SCA6. While both the major and minor axes of the ventral pons were proportionally decreased in SCA1, the minor axis was more decreased than the major axis in MJD. In SCA6, a mild reduction in the ratio of the ventral pontine area to the posterior fossa area (Pv/PF) was observed as well as obvious cerebellar atrophy. These findings indicate that in MR images SCA1, MJD and SCA6 show different atrophic features of the cerebellum and brainstem.

Adult↗

PubMed2006

Malignancy-associated vessel tortuosity: a computer-assisted, MR angiographic study of choroid plexus carcinoma in genetically engineered mice.

BACKGROUND AND PURPOSE: The ability to assess tumor malignancy and monitor treatment response noninvasively would be of value to both clinicians and animal investigators. This report describes the MR imaging characteristics of a genetically engineered mouse model of choroid plexus carcinoma (CPC) during tumor growth and progression to malignancy. We assess the ability of vessel tortuosity measurements, as calculated from high-resolution MR angiographic (MRA) images, to detect emerging CPC cancers. METHODS: MR images of 9 healthy mice and of 20 CPC mice with precancerous choroid dysplasia or with cancer over a wide range of sizes were analyzed. Two vessel tortuosity measures and a measure of vessel attenuation (vessel count) were calculated from MRA images. Malignancy assessment was based upon a statistical analysis of vessel tortuosity, by using an equation derived from an earlier study of human brain tumor patients. RESULTS: Choroid dysplasia was correctly judged nonmalignant. On the basis of vessel count, neoangiogenesis could not be detected until cancers were full-blown and had reached a volume of approximately 80 mm3. Vessel tortuosity measurements, however, correctly identified emerging malignancy in lesions larger than 0.3 mm3. CONCLUSION: To the best of our knowledge, this report provides the first description of in vivo, MR imaging characteristics of genetically engineered CPC mice during the progression from dysplasia to cancer. Vessel tortuosity measurements offer promise of correctly defining even tiny tumors as malignant.

Animals↗

PubMed2005

Monitoring proteasome activity in cellulo and in living animals by bioluminescent imaging: technical considerations for design and use of genetically encoded reporters.

The ubiquitin-proteasome pathway is the central mediator of regulated proteolysis, instrumental for switching on and off a variety of signaling cascades. Deregulation of proteasomal activity or improper substrate recognition and processing by the ubiquitin-proteasome machinery may lead to cancer, stroke, chronic inflammation, and neurodegenerative diseases. Quantifying total and substrate-specific proteasome activity in intact cells and living animals would enable analysis in vivo of proteasomal regulation and facilitate the screening and validation of potential modulators of the proteasome or its substrates. We discuss examples of tetra-ubiquitin or IkappaBalpha fused to firefly luciferase as genetically encoded reporters for monitoring total and IkappaBalpha-specific proteasomal activity by bioluminescence imaging. Such technology enables repetitive, temporally resolved, and regionally targeted assessment of proteasomal activity in vivo.

Animals↗

PubMed1999

Application of the RLGS image analysis tool (RAT) to the construction of a genetic linkage map of recombinant inbred strain SMXA.

The construction of a genetic linkage map is the first, fundamental step to analyze the genetic properties of any organism. For this purpose, the restriction landmark genome scanning method (RLGS) can be used and has been shown to have high productivity in various genetic analyses. However, construction of a genetic linkage map by the RLGS method is laborious, because hundreds of spots must be scored, usually by visual observation. In order to reduce human involvement in the data processing, we developed an image analysis software, RAT (RLGS Analysis Tool). We evaluated its accuracy and feasibility by comparing the parental distribution patterns of RLGS spots obtained by RAT and by human observation, using Syrian hamster strain backcross progeny. We then used RAT to construct a genetic linkage map of the recombinant inbred strain SMXA. We were able to obtain 121 progenitor strain-specific spots that were assigned to a specific chromosome.

Animals↗

PubMed2002

Schizophrenia: diverse approaches to a complex disease.

Schizophrenia is a debilitating mental illness that affects 1% of the population. Despite intensive study, its molecular etiology remains enigmatic. Like many common diseases, schizophrenia is multifactorial in origin, with both genetic and environmental contributions likely playing an important role in the manifestation of symptoms. Recent advances based on pharmacological studies, brain imaging analyses, and genetic research are now converging on tantalizing leads that point to a central role for several neurotransmitters, including dopamine, glutamate, and serotonin, that may interface with neurodevelopmental defects reflecting disease-related genetic aberrations. Here, we provide a brief overview of the parallel approaches being used to identify the molecular causes of schizophrenia and discuss possible directions for future research.

Antipsychotic Agents↗