bluuebunny/crossref_metadata_2025 huggingface dataset:
A potential model for early stages of chromosomal evolution via concentric Robertsonian fans: a large area of polymorphism in southern short-tailed shrews (Blarina carolinensis)
Authors: Qumsiyeh M.B. , Barker S. , Dover S. , Kennedy P.K. , Kennedy M.P.
Published: April 2003

Western Tennessee contains unusually highly polymorphic populations of southern short-tailed shrews (Blarina carolinensis). We previously documented eight Robertsonian translocations (ROBs) accounting for a variation in diploid number from 46 in most of this species’ range to 34–40 in western Tennessee. We have now expanded our study to include data from adjacent areas in Tennessee and Mississippi, 10 localities in all. The new data show a variation in diploid number ranging from 31 to 41, four new ROBs (for a total of 12), and the novel finding of monobrachial translocations in this group. All animals collected from this large area (extending over 12,000 km2) had some level of ROBs, and none represented the 2n = 46 form seen in other parts of the range of this species. Because other species of shrews (genus Sorex) are not affected in the same area, the factors and/or selective forces causing this extensive polymorphism in B. carolinensis must be unique to this species and to this geographic area. Some ROBs were found throughout this large area of over 12,000 km2. Other translocations (including those with monobrachial homology) were located in one or two localities in this large area, and still other translocations were intermediate in their distribution. There was a concentric pattern to the evolution and presumed spreading of the ROBs. This allowed us to expand the concept of a Robertsonian “fan,” introduced by Matthey (1970), to that of concentric evolution of multiple fusion fans: ROBs likely arose independently, separated temporally and geographically, and radiated into surrounding populations to create this complex zone of polymorphism. This is an active process in its infancy, and it is not as mature as that seen in European studies of Mus and Sorex.
Structural unbalanced chromosome rearrangements resolved by comparative genomic hybridization
Authors: Daniely M. , Barkai G. , Goldman B. , Aviram-Goldring A.
Published: April 2003

The identification of unbalanced structural chromosome rearrangements using conventional cytogenetic techniques depends on recognition of the unknown material from its banding pattern. Even with optimally banded chromosomes, when large chromosome segments are involved, cytogeneticists may not always be able to determine the origin of extrachromosomal material and supernumerary chromosomes. We report here on the application of comparative genomic hybridization (CGH), a new molecular-cytogenetic assay capable of detecting chromosomal gains and losses, to six clinical samples suspected of harboring unbalanced structural chromosome abnormalities. CGH provided essential information on the nature of the unbalanced aberration investigated in five of the six samples. This approach has proved its ability to resolve complex karyotypes and to provide information when metaphase chromosomes are not available. In cases where metaphase chromosome spreads were available, confirmation of CGH results was easily obtained by fluorescence in situ hybridization (FISH) using specific probes. Thus the combined use of CGH and FISH provided an efficient method for resolving the origin of aberrant chromosomal material unidentified by conventional cytogenetic analysis.
The pig aminoacylase 1 (ACY1) and ribosomal protein L29 (RPL29)/heparin/heparan sulfate interacting protein (HIP) genes are located together at 13q21→q22, corresponding to human 3p21.1
Authors: Sawazaki T. , Minezawa M.
Published: April 2003

The pig aminoacylase 1 (ACY1; N-acylamino acid aminohydrolase) gene was isolated from a pig cosmid library and characterized. The gene spans about 4.7 kb and consists of 15 exons. Fluorescence in situ hybridization found ACY1 to be located on pig chromosome 13 in the region q21→q22. This result and previous reports show that a large part of pig chromosome 13 corresponds to human chromosome 3. BLAST search results reveal that chromosome 13 contains a transcript similar to human ribosomal protein L29 (RPL29)/heparan sulfate/heparin-interacting protein (HIP). The transcript lies near the 3′-flanking region of the pig ACY1 gene; the 2 genes are linked tail-to-tail. The deduced amino acid sequence shows distinct homology to human RPL29/HIP, 96% identical in the N-terminal region. In the corresponding human 3p21.1 region, a deletion closely linked to the ACY1 locus has been observed in carcinoma cells. This suggests that a tumor suppressor gene is located in this region. Comparative mapping suggests also that the human RPL29/HIP gene may be near ACY1. Because many growth factors and cytokines interact with cells via heparin/heparan sulfate–proteoglycan, RPL29/HIP may play an important role on the cell surface by modulating interactions between cells and extracellular molecules.
Characterization of chromosomal abnormalities in prostate cancer cell lines by spectral karyotyping
Authors: Pan Y. , Kytölä S. , Farnebo F. , Wang N. , Lui W.O. , Nupponen N. , Isola J. , Visakorpi T. , Bergerheim U.S.R. , Larsson C.
Published: April 2003

Human prostate cancer is characterized by multiple gross chromosome alterations involving several chromosome regions. However, the specific genes involved in the development of prostate tumors are still largely unknown. Here we have studied the chromosome composition of the three established prostate cancer cell lines, LNCaP, PC-3, and DU145, by spectral karyotyping (SKY). SKY analysis showed complex karyotypes for all three cell lines, with 87, 58/113, and 62 chromosomes, respectively. All cell lines were shown to carry structural alterations of chromosomes 1, 2, 4, 6, 10, 15, and 16; however, no recurrent breakpoints were detected. Compared to previously published findings on these cell lines using comparative genomic hybridization, SKY revealed several balanced translocations and pinpointed rearrangement breakpoints. The SKY analysis was validated by fluorescence in situ hybridization using chromosome-specific, as well as locus-specific, probes. Identification of chromosome alterations in these cell lines by SKY may prove to be helpful in attempts to clone the genes involved in prostate cancer tumorigenesis.
Genetic mapping of the rat Lcn2 gene to chromosome 3
Authors: Chen K.-S. , Shepel L.A. , Stoesz S.P. , Brasic G.M. , Gould M.N.
Published: April 2003

The expression of rat 24p3, encoded by the Lcn2 gene, has been associated with rat mammary carcinomas initiated by the neu oncogene (Stoesz and Gould, 1995). In this study, we assign the Lcn2 gene to rat chromosome band 3q12 by genetic linkage analysis.
Micro- and macrochromosome paints generated by flow cytometry and microdissection: tools for mapping the chicken genome
Authors: Griffin D.K. , Haberman F. , Masabanda J. , O’Brien P. , Bagga M. , Sazanov A. , Smith J. , Burt D.W. , Ferguson-Smith M. , Wienberg J.
Published: April 2003

Despite the chicken being one of the most genetically mapped of all animals, its karyotype remains poorly defined. This is primarily due to microchromosomes that belie assignment by conventional methods. To address this problem, we have developed chromosome-specific paints using flow cytometry and microdissection. For the microchromosomes it was necessary to amplify and label DNA from single microdissected chromosomes.
Association of genomic imbalances with resistance to therapeutic drugs in human melanoma cell lines
Authors: Nessling M. , Kern M.A. , Schadendorf D. , Lichter P.
Published: April 2003

The reason why human malignant melanomas respond poorly to chemotherapy is not known. In an attempt to identify genes responsible for such resistance or sensitivity to therapeutic drugs, we studied the parental human melanoma cell line MeWo, as well as eight drug-resistant sublines of MeWo. These have low and high levels of resistance to four chemotherapeutic drugs with different modes of action: Vindesine, cisplatin, fotemustine and etoposide. Comparative genomic hybridizations with genomic DNA from these cell lines as probes revealed a number of chromosome gains and losses which occurred upon selective pressure during development of the sublines. The MeWo subline with high resistance to the topoisomerase II inhibitor, etoposide, exhibited the highest number of acquired chromosome imbalances. Interestingly, the two lines with high resistance to cisplatin and fotemustine, respectively, shared three additional imbalances, loss of 9p, loss of distal 12p and gain on distal 15q. The importance of these coincident imbalances is discussed.
Mapping of AKT3, encoding a member of the Akt/protein kinase B family, to human and rodent chromosomes by fluorescence in situ hybridization
Authors: Murthy S.S. , Tosolini A. , Taguchi T. , Testa J.R.
Published: April 2003

Previously, a rodent cDNA encoding the third member of the Akt/PKB family of serine/threonine kinases was cloned. We have now cloned the human homolog of this cDNA, and we have used this clone to map the AKT3 gene to human chromosome 1q44 by fluorescence in situ hybridization (FISH). We have also mapped the rodent homologs of AKT3 to rat chromosome 13q24→q26 and mouse chromosome 1H4–6 by FISH.
Eukaryotic translation termination factor gene (ETF1/eRF1) maps at D5S500 in a commonly deleted region of chromosome 5q31 in malignant myeloid diseases
Authors: Guenet L. , Henry C. , Toutain B. , Dubourg C. , Le Gall J.Y. , David V. , Le Treut A.
Published: April 2003

The human genome contains four ETF1 (eukaryotic translation termination factor 1) homologous sequences, localized on chromosomes 5, 6, 7 and X, and corresponding to a functional gene on chromosome 5 and three processed pseudogenes on the other chromosomes. ETF1 genomic or cDNA probes were mapped by fluorescence in situ hybridization to 5q31, 6p21, 7q11 and Xp11.4→p11.1. A microsatellite marker (D5S500) was identified in intron 7 of the functional ETF1 gene providing its exact position in the 5q31 band. Thus, the ETF1 gene is located in a 5q region which contains unidentified genes responsible for genetic or malignant disorders, and it might be considered as a candidate gene involved in the pathogenesis of these diseases.
Spectral karyotyping of the human colon cancer cell lines SW480 and SW620
Authors: Melcher R. , Steinlein C. , Feichtinger W. , Müller C.R. , Menzel T. , Lührs H. , Scheppach W. , Schmid M.
Published: April 2003

The cell lines SW480 and SW620, derived from different stages of colon carcinoma in the same patient, have been used for a number of biochemical, immunological, and genetic studies on colon cancer. A comparative analysis of their karyotypes may identify chromosomal aberrations that might represent markers for metastatic spread. In the present study spectral karyotyping (SKY) was applied to these two colon cancer cell lines. Compared to previously reported G-banded karyotypes, 9 (SW480) and 7 (SW620) markers were identical, 3 (SW480) and 3 (SW620) markers could be redefined, 5 (SW480) and 8 (SW620) markers were newly identified, and 4 (SW480) and 5 (SW620) of the previous described markers could not be confirmed. The redefined aberrations include very complex rearrangements, such as a der(16) t(3;16;1;16;8;16; 1;16;10) and a der(18)t(18;15;17)(q12; p11p13;??) in SW620 and a der(19)t(19;8;19;5) in SW480, that have not been identified by conventional banding techniques. The resulting chromosome gains (5q11→5q15, 7pter→q22, 11, 13q14→qter, 20pter→p12, X) and losses (8pter→p2, 18q12→qter, Y) found in both SW480 and SW620 were in good agreement with those frequently described in colorectal tumors as primary changes in the stem cell. Abnormalities found exclusively in SW620 cells only (gains of 5pter→5q11, 12q12→q23, 15p13→p11, and 16q21→q24 and losses of 2pter→2p24, 4q28→qter, and 6q25→qter) can be viewed as changes that occurred in a putative metastatic founder cell.
Identification and characterization of mouse orthologs of the AMMECR1 and FACL4 genes deleted in AMME syndrome: orthology of Xq22.3 and MmuXF1–F3
Authors: Vitelli F. , Meloni I. , Fineschi S. , Favara F. , Tiziana Storlazzi C. , Rocchi M. , Renieri A.
Published: April 2003

The contiguous gene deletion syndrome AMME is characterized by Alport syndrome, midface hypoplasia, mental retardation and elliptocytosis and is caused by a deletion in Xq22.3, comprising several genes including COL4A5, FACL4 and AMMECR1. We have now cloned the murine Facl4 and Ammecr1 genes and have mapped both novel murine genes to mouse chromosome X band F1–F3. The murine and human orthologs show 96.5% (FACL4) and 95.2% (AMMECR1) identity at the amino acid level, with conservation of the respective putative subcellular localization signals. Our results show that Facl4 and Ammecr1 are the true murine orthologs of the human genes. Furthermore, the mapping of Facl4 and Ammecr1 to MmuXF1–F3 suggests that this subinterval is orthologous, at least for a portion of Xq22.3.
Chromosomal localization of the genes encoding ALDH, BMP-2, R-FABP, IFN-γ, RXR-γ, and VIM in chicken by fluorescence in situ hybridization
Authors: Guttenbach M. , Nanda I. , Brickell P.M. , Godbout R. , Staeheli P. , Zehner Z.E. , Schmid M.
Published: April 2003

Six structural genes encoding ALDH, BMP-2, R-FABP, IFN-γ, RXR-γ and VIM were mapped in the chicken by fluorescence in situ hybridization (FISH) using genomic and cDNA clones as probes. The genes were found to be located on four different macrochromosomes: chromosome 1 (IFNG and FABP), chromosome 2 (VIM and ALDH), chromosome 3 (BMP2) and a smaller macrochromosome, most probably chromosome 7 (RXRG). With the exception of IFNG none of the newly mapped sites corresponds to known orthologous regions between chicken and human chromosomes.
Expression map of human chromosome region 17p13.3, spanning the RP13 dominant retinitis pigmentosa locus, the Miller-Dieker lissencephaly syndrome (MDLS) region, and a putative tumour suppressor locus
Authors: McHale J.C. , McKie A.B. , Tarttelin E.E. , Inglehearn C.F.
Published: April 2003

Chromosome region 17p13.3 is rich in genes, with 223 expressed sequence tags (ESTs) within the last 15 cM (7 Mb) of chromosome 17p in the GeneMap database. Loci for dominant retinitis pigmentosa (RP13), central areolar choroidal dystrophy (CACD), anterior polar cataract (CTAA2), Miller-Dieker lissencephaly syndrome (MDLS), and a region of tumour loss of heterozygosity (LOH) distinct from TP53 all map into the region adjacent to the 17p telomere. To date, however, there is no physical map of the region, which has resisted the efforts of the CEPH and Whitehead physical mapping programmes to generate contiguous clones across it. We have created a physical map covering approximately 3.5 Mb (6 cM)in this region, spanning the RP13 interval and extending distally to the gene MDCR (formerly, LIS1), which, when deleted, leads to the MDLS phenotype. The region covered is also the point of maximum LOH in lung cancer and has been implicated in the pathogenesis of many other human cancers. The map orders 47 sequence tagged sites, including 32 genes or ESTs, nine genetic markers, four anonymous sequences, and two YAC end clones, and highlights new candidate ESTs for involvement in RP13, MDLS, CTAA2, and a tumour-susceptibility gene.
Genomic organization, proposed alternative splicing mechanisms, and RNA editing structure of GRIK1
Authors: Barbon A. , Barlati S.
Published: April 2003

In the present study, we report the genomic reconstruction of the glutamate receptor GluR5 gene (GRIK1, alias GLUR5; 402 kb) by the use of the data available in public databases. This analysis allowed characterization of the exon-intron boundaries, identification of the gene promoter region, presentation of the putative complete sequences of two GluR5 mRNA isoforms, and definition of the structure of GluR5 pre-mRNA surrounding the Q/R editing site.
Comparison of genomic structures of four members of β-galactoside α2,3-sialyltransferase genes in the mouse
Authors: Takashima S. , Tsuji S.
Published: April 2003

The mouse genes encoding β-galactoside α2,3-sialyltransferases—Siat4 (ST3Gal I), Siat5 (ST3Gal II), Siat3 (ST3Gal III), and Siat4c (ST3Gal IV)—were isolated and characterized. Siat4 and Siat5 comprise 8.4 and 14 kb, respectively, and are composed of six exons each. The genomic structures of the two genes were similar. Siat3 and Siat4c comprise over 100 and 9.7 kb, respectively, and are composed of 12 and 10 exons, respectively. Although the genomic sizes of these genes differ, some of their exon structures are significantly similar. These results suggest that the gene pair Siat4 and Siat5 arose from a common ancestral gene, as did the two genes Siat3 and Siat4c.
Genomic localization of the human genes TAF1A, TAF1B and TAF1C, encoding TAFI48, TAFI63 and TAFI110 subunits of class I general transcription initiation factor SL1
Authors: Di Pietro C. , Rapisarda A. , Amico V. , Bonaiuto C. , Viola A. , Scalia M. , Motta S. , Amato A. , Engel H. , Messina A. , Sichel G. , Grzeschik K.-H. , Purrello M.
Published: April 2003

Human SL1 is a general transcription initiation factor (GTF) essential for RNA polymerase I to start rRNA synthesis at class I promoters. It is comprised of the TATA box-binding protein (TBP) and three TBP-associated factors (TAFI48, TAFI63 and TAFI110). We have determined that the human genes TAF1A, TAF1B and TAF1C, encoding these three TAFI polypeptides, are localized at lq42, 2p25 and 16q24, respectively. All three genes are present as single copies in the human genome and map to different chromosomes, as shown by somatic cell hybrid panel and radiation hybrid panel analysis and FISH. Two of these genes, TAF1C and TAF1B, are transcribed into multiple RNAs, as determined through Northern analysis of mRNA from various human organs and cell lines. If translated into different polypeptides, this could result in production of variant isoforms of SL1 with different activation potentials.
Direct visualization of the genomic distribution and organization of two cervid centromeric satellite DNA families
Authors: Li Y.-C. , Lee C. , Hsu T.-H. , Li S.-Y. , Lin C.C.
Published: April 2003

Several repetitive DNA fragments were generated from PCR amplifications of caribou DNA using primer sequences derived from the white-tailed deer satellite II DNA clone OvDII. Two fragments, designated Rt-0.5 and Rt-0.7, were sequenced and found to have 96% sequence similarity. These caribou clones also had 85% sequence similarity with OvDII. Multiple-colored fluorescence in situ hybridization (FISH) studies with satellite I and satellite II DNA probes to caribou metaphase chromosomes and extended chromatin fibers provided direct visualization of the genomic organization of these two satellite DNA families, with the following findings: (1) Cervid satellite I DNA is confined to the centromeric regions of the acrocentric autosomes, whereas satellite II DNA is found at the centromeric regions of all chromosomes except for the Y. (2) For most acrocentric chromosomes, the satellite I signal appeared to be medially located at the primary constriction, in contrast to that of satellite II, which appeared to be oriented toward the lateral sides as two separate fluorescent dots. (3) The satellite II clone Rt-0.7 appeared to be enriched in the centromeric region of the caribou X chromosome, a pair of biarmed autosomes, and a number of other acrocentric autosomes. (4) Fiber-FISH demonstrated that the satellite I and satellite II arrays were juxtaposed. On highly extended chromatin fibers, the total length of the hybridization signals for the two satellite DNA arrays often reached 300–400 μm. The length of a given satellite II array usually reached 200 μm, corresponding to 2 × 103 kb of DNA in a given centromere.
Genomic organization and assignment of VAMP2 to 17p12 by FISH
Authors: Zoraqi G.K. , Paradisi S. , Falbo V. , Taruscio D.
Published: April 2003

We describe the complete sequence, genomic organization, and FISH chromosome mapping of the human VAMP2. We identified a 7-kb clone, pISSHG2b3A, containing the entire structure of VAMP2. Previous studies performed by others identified a 5-kb clone, pVPC5-2, containing the incomplete VAMP2. The pVPC5-2 clone was partially sequenced and mapped to the broad region 17pter→p12 by somatic cell hybridization. Our clone overlaps the pVPC5-2 clone and extends ∼2 kb at the 3′ end. In this study, we mapped this gene more precisely on 17p12 by FISH and we found a new polymorphic microsatellite, (GT)7CC(GT)5, in exon V. This microsatellite, revealing three alleles with frequencies of 0.778, 0.139, and 0.083, might be useful for future linkage studies. Finally, we localized three previously known markers, stSG12859, TIGR-A002F11, and WIAF-1699 (alias stSG4044), in the 3′ untranslated region of the gene.
Isolation and characterization of a new FHL1 variant (FHL1C) from porcine skeletal muscle
Authors: Krempler A. , Kollers S. , Fries R. , Brenig B.
Published: April 2003

Four and a half LIM domain protein 1 (FHL1) was initially described as an abundant skeletal muscle protein with four LIM domains and a GATA like zinc finger. FHL1 was shown to be expressed in skeletal muscle as well as in a variety of other tissues. Recently, alternatively spliced FHL1 mRNAs were identified coding for C-terminal truncated proteins. The tissue distribution of these variants is more restricted and their functional properties seem to be different. We have isolated and characterized a new variant of FHL1 from porcine skeletal muscle (FHL1C). FHL1C is characterized by a newly identified start codon resulting in a 16 amino acids longer N- terminal region. We have isolated and characterized the porcine FHL1C gene spanning approximately 14 kb and harboring six exons. Using primer extension analysis, the transcription start site of FHL1C was mapped, indicating that FHL1C is regulated by an alternative promoter. The tissue distribution of FHL1C expression was studied by RT-PCR. The porcine FHL1C gene was assigned to the distal part of the long arm of the X chromosome by fluorescence in situ hybridization and screening of a somatic porcine/rodent cell hybrid panel.
Molecular cloning of Xp11 breakpoints in two unrelated mentally retarded females with X;autosome translocations
Authors: Nothwang H.G. , Schröer A. , van der Maarel S. , Kübart S. , Schneider S. , Rießelmann L. , Menzel C. , Hinzmann B. , Vogt D. , Rosenthal A. , Fryns J.-P. , Tommerup N. , Haaf T. , Ropers H.H. , Wirth J.
Published: April 2003

Mental retardation is a very common and extremely heterogeneous disorder that affects about 3% of the human population. Its molecular basis is largely unknown, but many loci have been mapped to the X chromosome. We report on two mentally retarded females with X;autosome translocations and breakpoints in Xp11, viz., t(X;17)(p11;p13) and t(X;20)(p11;q13). (Fiber-) FISH analysis assigned the breakpoints to different subbands, Xp11.4 and Xp11.23, separated by approximately 8 Mb. High-resolution mapping of the X- chromosome breakpoints using Southern blot hybridization resulted in the isolation of breakpoint-spanning genomic subclones of 3 kb and 0.5 kb. The Xp11.4 breakpoint is contained within a single copy sequence, whereas the Xp11.23 breakpoint sequence resembles an L1 repetitive element. Several expressed sequences map close to the breakpoints, but none was found to be inactivated. Therefore, mechanisms other than disruption of X-chromosome genes likely cause the phenotypes.
Spontaneous frequencies of aneuploid and diploid sperm in 10 normal Chinese men: assessed by multicolor fluorescence in situ hybridization
Authors: Shi Q. , Martin R.H.
Published: April 2003

Many studies have been published establishing the background frequencies of disomic and diploid sperm in normal men by fluorescence in situ hybridization (FISH) analysis, with highly significant variance among the reports. Besides interdonor heterogeneity and differences in the experimental protocols used, the question of inherent differences in chromosome malsegregation and meiotic arrest among different geographic and ethnic groups of donors has been raised. In this study, multicolor FISH analysis was carried out on semen samples from 10 nonsmoking, nondrinking Chinese men from the People’s Republic of China. The results were compared to FISH data on 10 nonsmoking, nondrinking Canadians under the same experimental conditions, in the same laboratory. A total of 200,497 sperm was scored in the Chinese donors and compared to 202,320 sperm from Canadian donors. Approximately 10,000 sperm per chromosome probe per donor were analyzed. The mean hybridization efficiency was 99.99%. The frequencies of X-bearing and Y-bearing sperm were not significantly different from the expected 50% for each individual and for the combined data from all donors (49.73% vs. 49.46%, P = 0.3946). The mean disomy frequencies (range) were 0.07% (0.02%–0.12%) for chromosome 13, 0.18% (0.09%–0.19%) for chromosome 21, 0.05% (0.01%–0.09%) for 24,XX, 0.02% (0.01%–0.06%) for 24,YY, and 0.29% (0.13%–0.49%) for 24,XY. The mean diploidy frequency (range) was 0.38% (0.22%–0.73%) for 13-21 hybridizations and 0.32% (0.07%–0.70%) for XY hybridizations. Highly significant interdonor heterogeneity was found for diploidy (P = 0.0000) and for XY disomy (P = 0.0011), but no age effect was observed in any category of disomic or diploid sperm. The data reported here show no marked differences in disomy and diploidy frequencies between the mainland Chinese and Canadian groups, if donor heterogeneity is taken into account.
Thrombo-Embolic Stroke, Moya-Moya Phenomenon and Primary Oxalosis
Authors: Lammie G. Alistair , Wardlaw Joanna , Dennis Martin
Published: April 2003

We present the clinical, radiological and autopsy findings in a 32-year-old woman with primary oxalosis, who suffered recurrent bilateral carotid territory infarcts. The overall features were those of moya-moya syndrome, with bilateral, ultimately thrombotic, occlusion of the distal internal carotid arteries. Vessel pathology suggests an underlying intimal vasculopathy, the possible relation of which to the patient’s metabolic abnormality is discussed.
Cheiroretroauricular Syndrome:A Restricted Form of Pure Sensory Stroke Due to a Pontine Hematoma
Authors: Ferro José M. , Pierre Tony
Published: April 2003

Pure sensory stroke is usually caused by a posterolateral thalamic lacune [1]. It has also been described in association with small intracerebral hemorrhages [2, 3], including a few located in the brainstem [4–12]. The sensory loss may involve the entire or a part of the hemibody, or have a cheiro-oral distribution [5, 7, 9, 10], being limited to the hand and the mouth or the perioral area of the same side. This particular distribution is related to damage to a restricted sector of fibers of the trigeminothalamic tract.
Vascular Risk Factors Linked to Multiple Lacunar Infarcts
Authors: Spolveri Stefano , Baruffi Maria Cristina , Cappelletti Carlo , Semerano Francesco , Rossi Stefania , Pracucci Giovanni , Inzitari Domenico
Published: April 2003

Background: The pathogenesis of lacunar infarcts is still incompletely established. Data from the literature suggest that vascular risk factors differ among patients with multiple (MLI) and single lacunar infarcts (SLI). We reexamined this hypothesis using stricter inclusion criteria and a less selected study population. Methods: We evaluated 136 patients consecutively admitted for first-ever minor stroke to a general hospital with the characteristics of a community hospital. Vascular risk factors were studied by univariate and multivariate statistical analyses among the following subgroups of patients, classified according to CT findings: (a) with lacunar infarct; (b) with nonlacunar infarct (NLI); (c) with SLI; (d) with MLI; (e) with single, either lacunar or nonlacunar, infarct. Results: No significant difference was observed between patients with lacunar infarcts and patients with NLI. Compared to patients with SLI or NLI, patients with MLI had significantly more often a family history of hypertension, cardiomegaly on the chest radiograph and CT leukoaraiosis as well as a higher systolic and diastolic blood pressure on admission. Logistic regression analysis selected CT leukoaraiosis, Rx cardiomegaly and admission diastolic blood pressure as independent, significant predictors of MLI. Conclusion: In patients with first-ever minor stroke, the risk factor profile differs according to the evidence of SLI or MLI on the CT scan. In terms of risk factors, patients with SLI seem more similar to those with NLI than those with MLI. Based on the predicting effect of variables linked with type and severity of arterial hypertension, the CT appearance of MLI might express a more univocal and specific cerebrovascular pathology (hypertensive arteriolosclerosis).
Incidence of Space-Occupying Brain Edema following Systemic Thrombolysis of Acute Supratentorial Ischemia
Authors: Rudolf J. , Grond M. , Stenzel C. , Neveling M. , Heiss W.-D.
Published: April 2003

Whether ‘malignant’ brain edema following ischemic stroke is due to or aggravated by reperfusion and therefore more frequent after thrombolytic therapy of stroke is still under debate. From 3/96 to 1/97, we treated 51 patients with acute supratentorial stroke within 3 h after symptom onset with rt-PA following a protocol similar to the NINDS study. The results of thrombolytic therapy were evaluated by repeated clinical examination and computed tomography (CT) during the first week after ictus. The incidence of space-occupying brain edema following intravenous thrombolytic therapy of acute ischemic stroke was lower than the edema frequency after conventional treatment, but mortality from ‘malignant’ edema was higher in the patients with thrombolysis. Thus, space-occupying edema after acute ischemic stroke may be aggravated by thrombolytic treatment. Forced reperfusion of already irreversibly damaged tissue increases edema formation and enlarges developing infarcts with a deleterious increase of intracranial pressure.
A New Type of Extracranial/Intracranial Bypass for Recurrent Haemodynamic Transient Ischaemic Attacks
Authors: Klijn Catharina J.M. , Kappelle L. Jaap , van der Grond Jeroen , van Gijn Jan , Tulleken Cornelis A.F.
Published: April 2003

Since the completion of the international extracranial/intracranial (EC/IC) bypass study in 1985, no treatment of proven value has become available for patients with symptomatic carotid artery occlusion other than treatment with antithrombotic medication. However, in this trial the causal factors of cerebral ischaemia were not part of the inclusion criteria and also patients with single episodes only were included. We report successful Excimer laser-assisted high flow EC/IC bypass surgery in a patient with frequent transient ischaemic attacks associated with a low flow state of the cerebral circulation. In the 1.5 years after the operation the patient has never again experienced any symptoms of cerebral ischaemia. In addition there was improvement in cerebral blood flow, measured by magnetic resonance spectroscopy and hexamethylpropyleneamine oxime single photon emission computed tomography. Certain patients with occlusion of the internal carotid artery may benefit from EC/IC bypass surgery, in particular the Excimer laser-assisted high-flow bypass, that is, if recurrent (transient) ischaemic attacks are associated with compromised cerebral perfusion.
Multinational Randomised Controlled Trial of Lubeluzole in Acute Ischaemic Stroke
Authors: Diener Hans Christoph
Published: April 2003

Background and Purpose: Lubeluzole is a benzothiazole derivative that has shown neuroprotective properties in different experimental models. This multicentre, double-blind, placebo-controlled trial was conducted to assess the safety and efficacy of lubeluzole in patients with an acute ischaemic stroke. Methods: Patients who presented with clinical signs and symptoms of acute cerebral hemispheric ischaemic stroke were randomised to intravenous therapy with placebo (n = 360) or lubeluzole 7.5 mg over 1 h followed by 10 mg/day for up to 5 days (n = 365). Treatment was initiated within 6 h of symptom onset. Mortality at 12 weeks was the primary end point. Secondary end points included neurological status (European Stroke Scale), functional outcome (Barthel Index), and disability level (Rankin Scale). The primary and secondary end points were all analysed using the protocol-defined Cochran-Mantel-Haenszel’s general association test. An additional analysis, the logistic regression approach, that included risk factors of age, baseline stroke severity and their interactions with treatment, was used to analyze outcome measures at 3 months. Results: In the total ischaemic stroke population, the overall mortality rate at 3 months was similar for lubeluzole (21.0%) and placebo (21.4%). The logistic regression model confirmed the effect of age on mortality risk, but showed that this was independent of treatment. Treatment benefit was related to stroke severity, as determined by the Clinical Global Impression rating, that is a pronounced clinically significant reduction in mortality was noted in the lubeluzole-treated patients for whom stroke severity was mild to moderate, but not in those for whom it was severe. This was found on the basis of a post hoc analysis not specified in the hypothesis. Lubeluzole did not increase morbidity among stroke survivors, as measured by the European Stroke Scale, Barthel Index and Rankin Scale. No safety concerns were seen with lubeluzole treatment. Conclusions: In the overall study population, treatment with intravenous lubeluzole within 6 h of the onset of ischaemic stroke did not affect mortality or clinical outcome. Among patients with mild to moderate ischaemic stroke, lubeluzole decreased mortality without increasing morbidity.
Knowledge of Stroke in Hong Kong Chinese
Authors: Cheung RaymondT.F. , Li LeonardS.W. , Mak Windsor , Tsang KinL. , Lauder IanJ. , Chan KoonH. , Fong GardianC.Y.
Published: April 2003

A random telephone survey on knowledge of stroke was conducted in 1,238 Hong Kong Chinese. Most respondents realized that effective treatment was available, that stroke was preventable and that it could be fatal or disabling. Sudden unilateral limb weakness, sudden speech and language disturbances, and sudden vertigo and clumsiness were better recognized than other warning symptoms of stroke. A slightly better recognition of symptoms of stroke was seen in those with a belief of knowing about stroke, providing a correct description of stroke, those with a positive household history of stroke and those with a better knowledge of potential risk factors. Most respondents would choose desirable actions if stroke was suspected in their family members or themselves. Friends and relatives, newspapers and magazines, and mass media provided the major sources of their knowledge.
Cerebrovascular Reactivity Evaluated by Transcranial Doppler: Reproducibility of Different Methods
Authors: Totaro Rocco , Marini Carmine , Baldassarre Massimo , Carolei Antonio
Published: April 2003

Transcranial Doppler is routinely used to assess the cerebrovascular reactivity, despite scarce information on its reproducibility. We evaluated the reproducibility of cerebrovascular reactivity measurements by this method utilizing different vasodilatory and vasoconstrictor stimuli. The cerebrovascular reactivity was measured in 45 healthy volunteers during hypercapnia induced by inhalation of a mixture of 5% CO2 and 95% O2, breath holding and rebreathing, and during hypocapnia induced by voluntary hyperventilation. Three sets of measurements were performed at times 0, 1, and 24 h to assess the within-observer short- and long-term reproducibility. The reproducibility was analyzed using the intraclass correlation coefficient. For the CO2 inhalation method, a good short-term (rI = 0.55; 95% CI = 0.39–0.68) and a good long-term (rI = 0.43; 95% CI = 0.25–0.59) reproducibility was found. For the breath-holding method a good short-term agreement was found (rI = 0.41; 95% CI = 0.22–0.57), while the long-term reproducibility was poor (rI = 0.17; 95% CI = –0.03–0.36). Rebreathing showed a fair (rI = 0.31; 95% CI = 0.11–0.48) short-term and a poor (rI = 0.17; 95% CI = –0.03–0.36) long-term reproducibility. For voluntary hyperventilation, the short-term reproducibility was good (rI = 0.53; 95% CI = 0.36–0.66), and the long- term reproducibility was fair (rI = 0.31; 95% CI = 0.11–0.48). In our study, CO2 inhalation and voluntary hyperventilation had the highest reproducibility and should be preferred when assessing cerebral vasoreactivity, especially in follow-up studies.
Positional Vertebrobasilar Transient Ischaemic Attacks Treated with Vertebral Angioplasty
Authors: Ruigrok Ynte , Cox Tim C.S. , Markus Hugh S.
Published: April 2003

We report the case of a man presenting with a brain-stem stroke from which he recovered fully, who developed right-sided weakness and numbness on walking despite no demonstrable postural fall in arterial blood pressure. Angiography revealed an occluded left vertebral artery, a tight stenosis at the origin of the right vertebral artery and non-patent left posterior communicating artery. Percutaneous transluminal angioplasty to the right vertebral stenosis results in a good angiographic result, and remission of symptoms which has persisted for 1 year. Identification of such patients with vertebrobasilar positional haemodynamic symptoms due to a focal stenosis is important as angioplasty offers an effective therapeutic option.
Mapping the Ischaemic Penumbra with PET: Implications for Acute Stroke Treatment
Authors: Baron Jean-Claude
Published: April 2003

The ischaemic penumbra has been documented in the laboratory animal as a severely hypoperfused, non-functional, but still viable cortex surrounding the irreversibly damaged ischaemic core; with elapsing time, more penumbra gets recruited into the core, while tissue reperfusion is able to stop this deleterious process until a certain point in time. As saving the penumbra should improve clinical outcome, it should constitute the main target of acute stroke therapy. In a series of PET studies performed 5–18 h after stroke onset, we were able to (i) document, for the first time in man, the existence of tissue fulfilling operational criteria for penumbra in about one third of the cases; (ii) show that long-term neurological recovery is proportional to the volume of penumbra that eventually escapes infarction, and (iii) detect penumbral tissue as late as 16 h after symptom onset in occasional patients, suggesting the therapeutic window may be protracted in such cases. Mapping the penumbra in the individual patient with neuroimaging procedures should allow to formulate a pathophysiological diagnosis, and thus to design a rational management of the stroke patient and to improve the selection of candidates for therapeutic trials.
Abundance of Microembolic Signals Detected by Transcranial Doppler Ultrasound in a Patient with Eisenmenger’s Syndrome
Authors: Droste Dirk W. , Ritter Martin A. , Mönnig Gerold , Kemény Vendel , Breithardt Günter , Ringelstein E. Bernd
Published: April 2003

Background: Clinically silent circulating microemboli can be detected by transcranial Doppler sonography. Case Description: We report the case of a 45-year-old man with congenital cyanotic heart disease, elevated haematocrit, low platelet count and decreased protein C and protein S activity. Before and following several haemodilutions, we performed 5 1-hour transcranial Doppler recordings from one or both middle cerebral arteries (MCAs) on different days. The number of microembolic signals per hour varied from 54 to 134. During the bilateral recording, the microemboli occurred on both sides (55 in the right and 45 in the left MCA, respectively). There was no relation to red blood cell count, platelet count, the spontaneously lowered prothrombin time or the spontaneously prolonged activated partial thromboplastin time. Conclusions: The origin of the large number of microembolic signals found in this patient remains unclear, but may be presumed in the intra-abdominal or crural venous system.
Stroke Prediction and Prevention by Carotid Endarterectomy: Keep an Eye on the Doughnut and Not Just the Hole
Authors: Hankey Graeme J.
Published: April 2003

Carotid endarterectomy is currently indicated for patients with severe symptomatic carotid stenosis because it halves the risk of stroke. However, it is expensive and potentially risky, and is performed unnecessarily in most of these patients. In order to improve the cost effectiveness of carotid endarterectomy, other predictors of stroke, in addition to the presence of recent focal neurological symptoms and the degree of carotid stenosis, need to be identified. Further research into the nature of the carotid atherosclerotic plaque and the clustering of systemic factors (infectious, inflammatory and vascular risk factors) that trigger inflammatory and morphological changes in the asymptomatic plaque and predispose it to rupture (with subsequent symptomatic thromboembolism) may yield powerful predictors of stroke which, when combined with the degree of stenosis and presence of focal neurological symptoms, may improve patient selection for carotid endarterectomy and its cost effectiveness.
Predictive Value of 99mTc-HMPAO-SPECT for Neurological Outcome/Recovery at the Acute Stage of Stroke
Authors: Marchal Gilles , Bouvard Gérard , Iglesias Serge , Sebastien Bernard , Benali Karim , Defer Gilles , Viader Fausto , Baron Jean-Claude
Published: April 2003

Background and Purpose: Combined perfusion and oxygen metabolism PET imaging is highly predictive of spontaneous outcome after middle cerebral artery (MCA) stroke, independent of clinical scores, but whether the assessment of perfusion alone by SPECT provides similar information remains unclear. We have assessed the prognostic value of 99mTc-HMPAO-SPECT at the acute stage of stroke. Methods: Twenty-seven first-ever nonhemorrhagic MCA territory stroke patients were prospectively studied 4–20 h (mean: 12 h) after onset with 99mTc-HMPAO-SPECT. None was part of a therapeutic trial or received thrombolysis. Neurological deficits were quantified at admission and 2 months later with Orgogozo’s MCA scale. SPECT images were visually classified by 3 independent observers into one of three patterns, as follows: pattern I = marked and extensive tracer hypofixation; pattern II = moderate and/or focal hypofixation with or without combined hyperfixation, and pattern III = normal or increased uptake without hypofixation. In addition to this visual analysis, we also calculated a voxel-based ‘hypoperfusion score’, an index of severity × extent of hypofixation according to Mountz’s method. Results: There was a good intra- and interobserver agreement. After consensus, 9, 14 and 4 patients were classified in patterns I, II and III, respectively. These patterns had a significant predictive value for raw outcome but not for percentage recovery (p = 0.008 and p = 0.127, respectively). Thus, all patients in pattern III had a good outcome, while most (but not all) patients in pattern I had a poor or intermediate outcome; pattern II patients were more evenly distributed among outcomes. Hypoperfusion scores were highly significantly positively correlated with both 2-month outcomes and percentage recoveries, even after controlling the predictive value of day 0 MCA scores by partial correlations. Comments: We found that SPECT had a significant added predictive value even when compared to admission neurological scores. Although less accurate than PET, 99mTc-HMPAO-SPECT may help to predict spontaneous individual neurological evolution, especially whenever perfusion images are normal or show an increased tracer uptake without associated hypofixation.
Cardioembolic vs. Noncardioembolic Strokes in Atrial Fibrillation: Frequency and Effect of Antithrombotic Agents in the Stroke Prevention in Atrial Fibrillation Studies
Authors: Hart R.G. , Pearce L.A. , Miller V.T. , Anderson D.C. , Rothrock J.F. , Albers G.W. , Nasco E.
Published: April 2003

Background: While atrial fibrillation (AF) increases the risk of cardioembolic stroke, some ischemic strokes in AF patients are noncardioembolic. Objectives: To assess ischemic stroke mechanisms in AF and to compare their responses to antithrombotic therapies. Methods: On-therapy analyses of ischemic strokes occurring in 3,950 participants in the Stroke Prevention in Atrial Fibrillation I–III clinical trials. Strokes were classified by presumed mechanism according to specified neurologic features by neurologists unaware of antithrombotic therapy. Results: Of 217 ischemic strokes, 52% were classified as probably cardioembolic, 24% as noncardioembolic, and 24% as of uncertain cause (i.e., 68% of classifiable infarcts were deemed cardioembolic). Compared to those receiving placebo or no antithrombotic therapy, the proportion of cardioembolic stroke was lower in patients taking adjusted-dose warfarin (p = 0.02), while the proportion of noncardioembolic stroke was lower in those taking aspirin (p = 0.06). Most (56%) ischemic strokes occurring in AF patients taking adjusted-dose warfarin were noncardioembolic vs. 16% of strokes in those taking aspirin. Adjusted-dose warfarin reduced cardioembolic strokes by 83% (p < 0.001) relative to aspirin. Cardioembolic strokes were particularly disabling (p = 0.05). Conclusions: Most ischemic strokes in AF patients are probably cardioembolic, and these are sharply reduced by adjusted-dose warfarin. Aspirin in AF patients appears to primarily reduce noncardioembolic strokes. AF patients at highest risk for stroke have the highest rates of cardioembolic stroke and have the greatest reduction in stroke by warfarin.
Dynamic But Not Static Cerebral Autoregulation Is Impaired in Acute Ischaemic Stroke
Authors: Dawson Suzanne L. , Blake Melanie J. , Panerai Ronney B. , Potter John F.
Published: April 2003

It remains unclear as to whether dynamic and static cerebral autoregulation (CA) are impaired in acute ischaemic stroke, and whether these changes are related to stroke subtype. This could have important implications with regard to post-stroke prognosis and the management of blood pressure (BP) in the acute post-ictal period. Using transcranial Doppler ultrasonography and non-invasive manipulation of BP, we compared both mechanisms in 61 patients with ischaemic stroke within 96 h of ictus, and 54 age- and sex-matched controls. There was no difference in static and dynamic CA indices between the various stroke subtypes. Combining all stroke subtypes dynamic autoregulation, as measured using thigh cuff release, was significantly impaired in both the affected and non-affected stroke hemispheres compared to controls (mean autoregulation index 4.1 ± 3.3, 4.8 ± 3.1 and 6.2 ± 2.3, respectively, p < 0.05). By comparison static autoregulation, assessed using isometric hand grip and thigh cuff inflation, was not significantly different. In conclusion, dynamic but not static CA appears to be globally impaired in acute ischaemic stroke. This deserves further study and may identify possibilities for therapeutic intervention.