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Biomedical subjects

Jiang Qian

Publications and source records attributed to Jiang Qian.

At least 37 records · Page 2Linked to original sources
PubMed2004

Comparative gene expression analysis of murine retina and brain.

PURPOSE: Several high-throughput studies have described gene expression in the central nervous system (CNS), and recently there has been increasing interest in analyzing how gene expression compares in different regions of the CNS. As the retina is often used as a model system to study CNS development and function, we compared retina and brain gene expression using microarray analyses. METHODS: Mouse retina, brain and liver RNA was hybridized to a custom cDNA microarray containing 5,376 genes and ESTs, and the data from the quantified scanned images were analyzed using Bioconductor and SAM. Preferential retina expression was confirmed by real-time PCR. The cellular distribution of genes newly identified as retina enriched genes was determined by immunohistochemistry. RESULTS: Using stringent statistical analyses we identified 733 genes that were preferentially expressed in retina and 389 in brain. The retina-liver hybridizations identified an additional 837 retina enriched genes. The cellular distribution in the retina was determined for two genes that had not previously been reported to be expressed in the retina, the transcription regulatory proteins EWS and PCPB1. Both proteins were found primarily in the inner nuclear layer. Finally, a comparison of the microarray data to publicly available SAGE and EST library databases demonstrated only limited overlap of the sets of retina enriched genes identified by the different methodologies. The preferential retinal expression of a subset of genes from the microarray, which were not identified as differentially expressed by other methods, was confirmed by quantitative PCR. CONCLUSIONS: The finding of differences in the groups of identified retina enriched genes from the various profiling techniques supports the use of multiple approaches to obtain a more complete description of retinal gene expression. Characterization of gene expression profiles of retina and brain may facilitate the understanding of the processes that underlie differences between the retina and other parts of the central nervous system.

Animals↗
PubMed2004

Threonine-17 phosphorylation of phospholamban: a key determinant of frequency-dependent increase of cardiac contractility.

Multiple studies have shown that phospholamban (PLN) plays a key role in regulation of frequency-dependent increase of cardiac contraction, a hallmark of the contractile reserve in myocardium. However, the mechanisms underlying this relationship remain elusive. Phosphorylation of PLN occurs on residues: serine-16 (Ser(16)) and threonine-17 (Thr(17)) in vivo. In isolated wild-type cardiomyocytes, we found that increases of stimulation frequency from 0.5 to 5 Hz were associated with increased Thr(17) phosphorylation of PLN and cardiac contractility. To further delineate the role of PLN phosphorylation in the frequency-dependent increases of cardiac function, three transgenic mouse models, expressing wild-type, Ser16Ala (S16A), or Thr17Ala (T17A) mutant PLN in the null background were generated. Transgenic lines expressing similar levels of wild-type or mutant PLN were selected and isolated cardiomyocytes were paced from 0.5 to 5 Hz. Upon increases in pacing frequency, the fractional shortening (FS) and rates of contraction (+dL/dt) and relaxation (-dL/dt) increased in wild-type and S16A mutant PLN cardiomyocytes. In contrast, in myocytes expressing the T17A mutant PLN, there were no increases in FS and +/-dL/dt upon increasing the frequency of stimulation. The time to 50% peak shortening (TTP(50)) and to 50% relaxation (TTR(50)) were also abbreviated to a much higher extent (two-fold) in wild-type and S16A mutant compared to T17A mutant PLN cardiomyocytes. These results indicate that Thr(17) phosphorylation of PLN is the major contributor to frequency-dependent increases of contractile and relaxation parameters in mouse cardiomyocytes, although some increases in these parameters occur even in the absence of PLN phosphorylation. Thus, the positive force-frequency relationship in cardiomyocytes is mechanistically and mainly related to PLN phosphorylation.

Animals↗
PubMed2004

Genetic and expression profiles of cerebellar liponeurocytomas.

Cerebellar liponeurocytoma, a rare, newly identified CNS neoplasm of adults, is characterized by advanced neuronal/neurocytic and focal lipomatous differentiation, low proliferative potential and a favorable clinical prognosis. Despite the different age distribution and benign biological behavior, the cerebellar liponeurocytoma shares several features with the cerebellar medulloblastoma, which may include an origin from the periventricular matrix of the fourth ventricle or the external granular layer of the cerebellum. To establish the genetic profile of cerebellar liponeurocytomas, we have formed an international consortium and collected tumor samples from 20 patients. DNA sequencing revealed TP53 missense mutations in 4 (20%) of 20 cerebellar liponeurocytomas, a frequency higher than in medulloblastomas. There was no case with PTCH, APC, or beta-catenin mutations, each of which may be present in subsets of medulloblastomas. Isochromosome 17q, a genetic hallmark of classic medulloblastomas, was not observed in any of the cases investigated by FISH analysis. cDNA array analyses were carried out on 4 cerebellar liponeurocytomas, 4 central neurocytomas, and 4 classic medulloblastomas. Cluster analysis of the cDNA expression data of 1176 genes grouped cerebellar liponeurocytomas close to central neurocytomas, but distinct from medulloblastomas. These results suggest cerebellar liponeurocytoma as a distinct tumor entity that is genetically different from medulloblastoma. Furthermore, the cDNA expression array data suggest a relationship to central neurocytomas, but the presence of TP53 mutations, which are absent in central neurocytomas, suggests that their genetic pathways are different.

Adult↗
PubMed2004

Identification of gene expression changes associated with the progression of retinal degeneration in the rd1 mouse.

PURPOSE: One approach to gaining insight into the biological pathways contributing to rod and cone photoreceptor death is to identify patterns of gene expression changes. In the present study, a custom retinal microarray was developed to analyze the rd1 mouse, a well-characterized animal model of human retinal degeneration. METHODS: A microarray was constructed containing cDNA fragments corresponding to genes known or postulated to be involved in normal retinal function, development, and disease. Gene expression in rd1 retina was compared with age-matched control retinas at three time points: the peak of rod degeneration (postnatal day [P]14), early in cone degeneration (P35), and during cone degeneration (P50). Selected microarray results were confirmed with real-time PCR. The cellular distribution of one of the differentially expressed genes, dickkopf 3 (Dkk3), was assessed by in situ hybridization. RESULTS: At each stage of degeneration, there was only limited overlap of the genes that showed increased expression, suggesting the involvement of temporally distinct molecular pathways. Genes active in transport mechanisms and in signaling pathways were differentially expressed during rod degeneration, whereas genes with functions in protein modification and cellular metabolism were differentially expressed during cone degeneration. Increased expression of genes involved in cell proliferation pathways and oxidative stress was observed at each time point. CONCLUSIONS: These microarray results provide clues to understanding the molecular pathways underlying photoreceptor degeneration and indicate directions for future studies. In addition, comparisons of normal and degenerated retina identified numerous genes and ESTs that are potentially enriched in rod photoreceptors.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Gene expression profiling of purified rat retinal ganglion cells.

PURPOSE: The phenotype of specialized cells arises, in part, from their characteristic gene expression patterns. Retinal ganglion cells (RGCs) are of wide interest in neuroscience and die in glaucoma and other optic neuropathies. In this study the genes expressed by RGCs were profiled by expressed sequence tag (EST) analysis. METHODS: ESTs were generated from a cDNA library constructed from RGCs isolated by immunopanning. The RGC genes were compared with published microarray expression profiles from 13 different neural regions. Immunohistochemistry was performed by standard methods. RESULTS: Clustering of 4791 RGC ESTs identified 2360 unique gene clusters. Of these, 60% represented known genes, 27% uncharacterized genes/ESTs, and 13% novel sequence. Unexpectedly, one of the largest RGC clusters, RESP18, corresponded to a neuroendocrine-specific gene preferentially expressed in the hypothalamus. RESP18 immunoreactivity within the retina was found mainly in the RGC layer. DDAH1, a gene involved in nitric oxide metabolism, was localized to RGC and amacrine layers. Comparison of gene expression patterns across neuronal regions revealed a prominent subset of RGC genes that were overexpressed in dorsal root and trigeminal ganglia. To narrow the search for candidate disease-related genes, RGC genes were mapped to known disease loci for optic neuropathies. CONCLUSIONS: This work is one of the first efforts to profile gene expression in a purified population of retinal neurons, the RGCs. The profiling, in addition to revealing both known and novel genes underlying the RGC phenotype, also uncovered common patterns of gene expression between RGCs and other sensory ganglia.

Animals↗
PubMed2004

Primary central nervous system posttransplant lymphoproliferative disorders.

Posttransplant lymphoproliferative disorders (PTLDs) represent a spectrum ranging from Epstein-Barr virus (EBV)-driven polyclonal lymphoid proliferations to EBV+ or EBV- malignant lymphomas. Central nervous system (CNS) PTLDs have not been characterized fully. We reviewed the clinical, radiologic, and pathologic features of 12 primary CNS PTLDs to define them more precisely. Patients included 10 males and 2 females (median age, 43.4 years) who were recipients of kidney (n = 5), liver (n = 2), heart (n = 2), peripheral blood stem cells (n = 2), or bone marrow (n = 1). All received immunosuppressive therapy. CNS symptoms developed 3 to 131 months (mean, 31 months) after transplantation. By neuroimaging, most showed multiple (3 to 9) intra-axial, contrast-enhancing lesions. Histologic sections showed marked expansion of perivascular spaces by large, cytologically malignant lymphoid cells that were CD45+, CD20+, EBV+ and showed light chain restriction or immunoglobulin gene rearrangement. In distinction to PTLDs in other organ systems, CNS PTLDs were uniformly high-grade lymphomas that fulfilled the World Health Organization criteria for monomorphic PTLDs. Extremely short survival periods were noted for each CNS PTLD that followed peripheral blood stem cell transplantation. Survival of others with CNS PTLD varied; some lived more than 2 years.

Adult↗
PubMed2004

A carcinoid tumor mimicking an isolated intracranial meningioma. Case report.

This 79-year-old woman presented with progressively worsening dementia, abulia, flat affect, urinary incontinence, and profuse watery diarrhea. Results of computerized tomography and magnetic resonance studies indicated an extraaxial, dural-based mass compressing the right frontal lobe and consistent with a convexity meningioma. A right frontal craniotomy was performed and the dural-based mass was resected. Histopathological features on immunostaining of the lesion were consistent with a carcinoid tumor (low-grade neuroendocrine carcinoma). Further evaluation revealed no primary carcinoid tumor in the foregut from which they typically originate. The authors concluded that this intracranial carcinoid tumor was the primary lesion despite its unusual location and that it should be included in the differential diagnosis of dural-based, extraaxial brain lesions.

Aged↗
PubMed2004

Preoperative stent placement for intradural vertebral artery stenosis from a rare xanthogranuloma. Case report.

In this report, the authors discuss a novel use of intradural vertebral artery (VA) stent placement to protect a tumor-encased vessel from injury during lesion resection. The tumor was a rare foramen magnum region xanthogranuloma and a component of Erdheim-Chester disease (ECD). This 64-year-old man presented with large masses encasing and compressing the intracranial segments of each VA. Preoperatively, a left VA stent was placed to protect the arterial wall during resection of the tumor. Histopathological study results on the subtotally resected mass were consistent with xanthogranuloma, a rare benign histiocytic tumor frequently occurring in patients with ECD. Further radiographic evaluation in the patient revealed an osteolytic lesion of the eleventh thoracic vertebra supporting the diagnosis of ECD disease. Based on this case study, the authors recommend the following: 1) tumor-encased vessels can be protected preoperatively by stent placement to assist with tumor debulking; and 2) patients diagnosed with a xanthogranuloma should be evaluated for multisystem involvement consistent with ECD.

Angioplasty, Balloon↗
PubMed2004

Intracranial neuromuscularchoristoma: a case report and literature review.

Neuromuscular choristoma (NMC) is an uncommon tumor that usually involves a large nerve trunk. Only 28 cases of NMC have been previously reported in the English-language literature, 17 of which involved cranial nerves. We report a new case of intracranial NMC that arose from a facial nerve at the cerebellopontine angle in a 44-year-old man. The patient was taken to surgery, where the lesion was found to involve the right facial nerve. The tumor was partially removed, and at the 2-year follow-up, the patient showed no sign of recurrence.

Adult↗
PubMed2003

Relationship between gene co-expression and probe localization on microarray slides.

BACKGROUND: Microarray technology allows simultaneous measurement of thousands of genes in a single experiment. This is a potentially useful tool for evaluating co-expression of genes and extraction of useful functional and chromosomal structural information about genes. RESULTS: In this work we studied the association between the co-expression of genes, their location on the chromosome and their location on the microarray slides by analyzing a number of eukaryotic expression datasets, derived from the S. cerevisiae, C. elegans, and D. melanogaster. We find that in several different yeast microarray experiments the distribution of the number of gene pairs with correlated expression profiles as a function of chromosomal spacing is peaked at short separations and has two superimposed periodicities. The longer periodicity has a spacing of 22 genes (approximately 42 Kb), and the shorter periodicity is 2 genes (approximately 4 Kb). CONCLUSION: The relative positioning of DNA probes on microarray slides and source plates introduces subtle but significant correlations between pairs of genes. Careful consideration of this spatial artifact is important for analysis of microarray expression data. It is particularly relevant to recent microarray analyses that suggest that co-expressed genes cluster along chromosomes or are spaced by multiples of a fixed number of genes along the chromosome.

Animals↗
PubMed2003

Prediction of regulatory networks: genome-wide identification of transcription factor targets from gene expression data.

MOTIVATION: Defining regulatory networks, linking transcription factors (TFs) to their targets, is a central problem in post-genomic biology. One might imagine one could readily determine these networks through inspection of gene expression data. However, the relationship between the expression timecourse of a transcription factor and its target is not obvious (e.g. simple correlation over the timecourse), and current analysis methods, such as hierarchical clustering, have not been very successful in deciphering them. RESULTS: Here we introduce an approach based on support vector machines (SVMs) to predict the targets of a transcription factor by identifying subtle relationships between their expression profiles. In particular, we used SVMs to predict the regulatory targets for 36 transcription factors in the Saccharomyces cerevisiae genome based on the microarray expression data from many different physiological conditions. We trained and tested our SVM on a data set constructed to include a significant number of both positive and negative examples, directly addressing data imbalance issues. This was non-trivial given that most of the known experimental information is only for positives. Overall, we found that 63% of our TF-target relationships were confirmed through cross-validation. We further assessed the performance of our regulatory network identifications by comparing them with the results from two recent genome-wide ChIP-chip experiments. Overall, we find the agreement between our results and these experiments is comparable to the agreement (albeit low) between the two experiments. We find that this network has a delocalized structure with respect to chromosomal positioning, with a given transcription factor having targets spread fairly uniformly across the genome. AVAILABILITY: The overall network of the relationships is available on the web at http://bioinfo.mbb.yale.edu/expression/echipchip

Algorithms↗
PubMed2003

Guillain-Barré syndrome associated with immune reconstitution.

We report a case of acute Guillain-Barré syndrome (GBS) associated with a prompt and vigorous immune reconstitution and decrease in the virus load noted during treatment with a potent regimen of highly active antiretroviral therapy. We hypothesize that GBS may have been due to an aberrant immune response or an adverse drug reaction in association with preexisting peripheral neurologic disease.

Anti-HIV Agents↗
PubMed2003

Genomic analysis of gene expression relationships in transcriptional regulatory networks.

From merging several data sources, we created an extensive map of the transcriptional regulatory network in Saccharomyces cerevisiae, comprising 7419 interactions connecting 180 transcription factors (TFs) with their target genes. We integrated this network with gene-expression data, relating the expression profiles of TFs and target genes. We found that genes targeted by the same TF tend to be co-expressed, with the degree of co-expression increasing if genes share more than one TF. Moreover, shared targets of a TF tend to have similar cellular functions. By contrast, the expression relationships between the TFs and their targets are much more complicated, often exhibiting time-shifted or inverted behavior. Further information is available at http://bioinfo.mbb.yale.edu/regulation/TIG/

Gene Expression Regulation↗
PubMed2003

Identification of novel genes preferentially expressed in the retina using a custom human retina cDNA microarray.

PURPOSE: To construct a custom cDNA microarray for comprehensive human retinal gene expression profiling and apply it to the identification of genes that are preferentially expressed in the retina. METHODS: A cDNA microarray was constructed based on the predicted human retina gene expression profile according to expressed sequence tag (EST) databases. Gene expression profiles were obtained from five human retinas, two livers, and the cerebral cortical regions of two brains. Each sample was studied in duplicate, using a reference sample experimental design. Retina-enriched genes were identified by using the significance analysis for microarray (SAM) algorithm. Quantitative real time PCR was used to confirm microarray results. Bioinformatic analysis was performed to compare the array results with expression data available from public databases. RESULTS: The cDNA microarray contains 10,034 sequences: 67% represent known genes and 33% represent ESTs. Differential hybridization with the array identified, in addition to known retinal genes, 186 retina-enriched genes that do not have known retinal function. Of these, 96 represent novel genes. Quantitative real-time PCR of 11 of the identified genes and ESTs confirmed their retina-enriched expression pattern. Bioinformatic analysis of EST databases suggests that of the 186 genes, approximately 40% are predominantly expressed in the retina, whereas the remainder show significant expression in other tissues. Comparison of this study's microarray-based retina-enriched gene set with three published similar sets identified using complementary high-throughput approaches demonstrated only limited overlap of the identified genes. CONCLUSIONS: Because previous studies have demonstrated that many retina-enriched genes are crucial for maintaining normal retinal function, the genes identified here are likely to include ones that have important roles in the retina and ones that when mutated can cause or modulate retinal disease. In addition, the retina custom array should provide a useful resource for comparing expression profiles between normal and diseased human retinas.

Adult↗
PubMed2002

Complex transcriptional circuitry at the G1/S transition in Saccharomyces cerevisiae.

In the yeast Saccharomyces cerevisiae, SBF (Swi4-Swi6 cell cycle box binding factor) and MBF (MluI binding factor) are the major transcription factors regulating the START of the cell cycle, a time just before DNA replication, bud growth initiation, and spindle pole body (SPB) duplication. These two factors bind to the promoters of 235 genes, but bind less than a quarter of the promoters upstream of genes with peak transcript levels at the G1 phase of the cell cycle. Several functional categories, which are known to be crucial for G1/S events, such as SPB duplication/migration and DNA synthesis, are under-represented in the list of SBF and MBF gene targets. SBF binds the promoters of several other transcription factors, including HCM1, PLM2, POG1, TOS4, TOS8, TYE7, YAP5, YHP1, and YOX1. Here, we demonstrate that these factors are targets of SBF using an independent assay. To further elucidate the transcriptional circuitry that regulates the G1-to-S-phase progression, these factors were epitope-tagged and their binding targets were identified by chIp-chip analysis. These factors bind the promoters of genes with roles in G1/S events including DNA replication, bud growth, and spindle pole complex formation, as well as the general activities of mitochondrial function, transcription, and protein synthesis. Although functional overlap exists between these factors and MBF and SBF, each of these factors has distinct functional roles. Most of these factors bind the promoters of other transcription factors known to be cell cycle regulated or known to be important for cell cycle progression and differentiation processes indicating that a complex network of transcription factors coordinates the diverse activities that initiate a new cell cycle.

Binding Sites↗
PubMed2002

The dominance of the population by a selected few: power-law behaviour applies to a wide variety of genomic properties.

BACKGROUND: The sequencing of genomes provides us with an inventory of the 'molecular parts' in nature, such as protein families and folds, and their functions in living organisms. Through the analysis of such inventories, it has been shown that different genomes have very different usage of parts; for example, the common folds in the worm are very different from those in Escherichia coli. RESULTS: Despite these differences, we find that the genomic occurrence of generalized parts follows a well-known mathematical framework called the power law, with a few parts occurring many times and most occurring only a few times. This observation is true in a wide variety of genomic contexts. Earlier studies found power laws in a few specific cases, such as the occurrence of protein families. Here, we find many further cases of power-law behavior, for example in the occurrence of pseudogenes and in levels of gene expression. We show comprehensively that this behavior applies across many different genomes, for many different types of parts (DNA words, InterPro families, protein superfamilies and folds, pseudogene families and pseudomotifs), and for the many disparate attributes associated with these parts (their functions, interactions and expression levels). CONCLUSIONS: Power-law behavior provides a concise mathematical description of an important biological feature: the sheer dominance of a few members over the overall population. We present this behavior in a unified framework and propose that all these observations are connected to an underlying DNA duplication process as genomes evolved to their current state.

Animals↗