bluuebunny/crossref_metadata_2025 huggingface dataset:
‘Tweaked’ GammaPlan for Target Volume Measurement in Non-Fiducial Based Images: A Simple Routine for Follow-Up Assessment
Authors: Cheung J.Y.C. , Yu C.P. , Ho R.T.K.
Published: April 2003

The GammaPlan provides accurate estimation of target volume. However, a stereotactic frame and fiducials are required. At follow-up MR/CT, fiducials are no longer available. Surgeons rely on visual impression, 2-D measurements, or other methods to estimate the volume of the treated targets. These methods are not objective and may give rise to misleading conclusions. By modifying the image header files of GammaPlan version 3, it is possible to scale the images which are not acquired with stereotactic fiducials. The target is then mapped and its volume measured as usual. The target volumes in 7 patients were measured by the tweaked GammaPlan and compared with volume measurements using the standard version. The mean error was less than 2%. In a separate study, phantom syringes with known volumes of water were used for MR imaging. The tweaked version again gave accurate volume estimation of the phantom syringes with a less than 5% error for most cases. This method has subsequently been used in all Gamma Knife follow-up cases. Significant volume changes have been detected where conventional assessment showed no apparent change. Moreover, such volume changes correlated with clinical improvement or deterioration. It is recommended that all Gamma Knife users report tumor response by volume change. Our method is simple, reliable and does not require additional cost.
Leksell’s Unpublished Pallidotomies of 1958–1962
Authors: Laitinen Lauri V.
Published: April 2003

Lars Leksell performed posteroventral pallidotomies in 123 parkinsonian patients from 1958 through 1962. This previously unpublished series was analyzed by the present author 40 years later. The analysis was based on a number of old radiographs that were found accidentally as well as the available hospital notes. After pallidotomy, Leksell had left metal markers in the brain to illustrate the lesion site. Superimposition of the markers on modern MRI scans of patients with similar-sized heads shows a high degree of accuracy of Leksell’s pallidotomy.
Frequency Analysis of Involuntary Movements during Wrist Tracking: A Way to Identify MS Patients with Tremor Who Benefit from Thalamotomy
Authors: Liu Xuguang , Aziz Tipu Z. , Miall R. Christopher , Rowe Jeremy , Alusi Sundus H. , Bain Peter G. , Stein John F.
Published: April 2003

To identify those multiple sclerosis (MS) patients with disabling tremor who will benefit most from thalamotomy, measurements of frequency spectra of involuntary movements during visually guided wrist tracking were carried out in 11 consecutive patients with MS before and after ventrolateral thalamotomy. Thalamotomy was significantly more effective if patients had disruptive action tremor which appeared as a single peak in the frequency spectra. Such patients showed an average reduction of nearly 80% in tremor magnitude after thalamotomy. In comparison, surgery produced an average reduction of only 30% in 3 other patients who had action tremor but showed multiple peaks in the frequency spectra. Frequency analysis of involuntary movements identifies those MS patients with disabling tremor who benefited most from thalamotomy.
In vivo Proton Magnetic Resonance Spectroscopy of Brain Tumors
Authors: Fountas Kostas N. , Kapsalaki Effie Z. , Gotsis Stathis D. , Kapsalakis John Z. , Smisson III Hugh F. , Johnston Kim W. , Robinson Jr. Joe Sam , Papadakis Nicholas
Published: April 2003

The ability of magnetic resonance spectroscopy (MRS) to differentiate neoplastic brain cells and their metabolic and structural characteristics is evaluated. We examined 120 patients with brain tumors using a 1.5-tesla MRI unit and MRS. The peak areas of N-acetyl-aspartate (NAA), phosphocreatine-creatine (Pcr-Cr), choline-containing compounds (Cho), lactate, lipids, myoinositol, amino acids and the ratios of NAA/Pcr-Cr, NAA/Cho and Cho/Pcr-Cr were calculated by a standard integral algorithm. In normal brain tissue, the following metabolites were identified: NAA at 2.0 ppm, Pcr-Cr at 3.0 ppm and Cho at 3.2 ppm. The different concentrations of the metabolites examined and their role in the biochemical profile of different types of tumors are discussed. The confidence interval of the MRS versus pathology was between 0.9 and 0.954, while it was between 0.52 and 0.631 for MRI versus pathology. The Cho/Pcr-Cr ratio is a very important malignancy marker for histologic tumor grading of astrocytomas. The greater this ratio, the higher the grade of the astrocytoma. NAA/Pcr-Cr together with Cho/Pcr-Cr help specify the presence or absence of a neoplasm. Proton MRS is a useful and promising diagnostic modality not only in diagnosing but also in grading solid brain tumors.
Acoustic Neuroma – Surgery or Radiosurgery?
Authors: Brophy Brian P.
Published: April 2003

This paper discusses surgery and radiosurgery from the author’s personal experience with both techniques. Multi-discipline assessment will allow the patient to make an informed decision regarding preferred management.
Factors Influencing Early Complications following Gamma Knife Radiosurgery
Authors: Majhail Navneet Singh , Chander Subhash , Mehta Veer Singh , Julka Pramod Kumar , Ganesh Tharmar , Rath Gaura Kishore
Published: April 2003

Purpose: The factors influencing early complications following Gamma Knife radiosurgery have not been definitely established. We report a prospective study evaluating the incidence of early complications (occurring within 3 months of radiosurgery) and various factors associated with early complications following stereotactic Gamma Knife radiosurgery for intracranial lesions. Patients and Methods: Seventy-nine previously unirradiated consecutive adult patients (82 lesions: arteriovenous malformations 35, benign tumors 43, metastases 4) treated by Gamma Knife radiosurgery were studied between May 1997 and August 1998. The median target volume was 4.8 cm3. The median dose of 15 Gy was prescribed to the 50% isodose. Patients were evaluated clinically and radiologically (with CT/MRI/SPECT) at 3-month intervals for the 1st year and 6 monthly thereafter. Complications were further divided as immediate (occurring within 24 h) or acute (occurring from 1 day to 3 months). Results: Early complications were observed in 19/79 (24.0%) patients. These included immediate in 10 (12.7%) and acute complications in 9 (11.3%) patients and were characterized by headache, nausea/vomiting, vertigo and seizures. No severe early complications were observed. Radiological changes in the form of perilesional edema were seen in 8/82 (9.8%) lesions. Maximum target diameter >25 mm was the only factor significantly associated with early complications by univariate analysis (p = 0.0335). Multivariate analysis revealed maximum target diameter >25 mm and prescribed dose >20 Gy to be significantly associated with early complications (p = 0.0442 and p = 0.0083, respectively). Conclusion: Up to one fourth of the patients undergoing Gamma Knife radiosurgery for intracranial lesions can experience self-limiting early toxicity. The selection of targets with small diameter and volume may reduce the risk of early complications following Gamma Knife radiosurgery.
Apoptosis in Prostatic Adenocarcinoma following Complete Androgen Ablation
Authors: Montironi R. , Pomante R. , Diamanti L. , Magi-Galluzzi C.
Published: April 2003

Objective: To analyze the cell death phenomenon in prostate cancer following complete androgen ablation. Methods: The frequency and location of apoptotic bodies (ABs) were evaluated in haematoxylin and eosin stained sections of radical prostatectomy specimens from patients with invasive prostatic adenocarcinoma treated with neo-adjuvant endocrine combination therapy for 3 months before surgery. The results were compared with an untreated age- and stage-matched control group. Results: Both in treated and untreated prostate tissue the AB frequency increased from normal prostate, through prostatic intraepithelial neoplasia, up to prostatic adenocarcinoma. The main location was in the cell layers adjacent to the stroma, their frequency decreasing towards the lumen. The frequency of ABs was higher in the treated prostate glands than in the untreated groups. The relative increase of the AB frequency in treated carcinomas as compared with untreated ones was lowest in tumours with a solid pattern, intermediate in the cribriform, and highest in the acinar pattern. Conclusions: Complete androgen ablation induces involution of prostate tissue mainly through the enhancement of apoptosis. This type of cell death is thought to play a major role and might be linked to specific changes in signal transduction mechanisms in response to hormonal withdrawal.
p53 Mutations and Other Prognostic Factors of Renal Cell Carcinoma
Authors: Girgin Cengiz , Tarhan Hüseyin , Hekimgil Mine , Sezer Akif , Gürel Gözen
Published: April 2003

Objective: Tumor stage, histological pattern, cell type, diameter and cell ploidy are the factor that have been proposed for predicting the prognosis of renal cell carcinoma (RCC). There is a wide variation in the reported incidence of p53 mutation in RCC, and its prognostic significance for this tumor is unknown. We investigated the prognostic value of p53 mutations among other prognostic factors. Patients and Method: We evaluated the stages, tumor diameters, histological grades, cellular patterns and the presence of mutant p53 protein in 50 cases of RCC. The survival function of each parameter was estimated by Kaplan-Meier and log-rank tests, and the significance of each parameter on survival was evaluated by logistic regression analysis. Results: The p53 mutation incidence was 20% in the RCC cases included in the study (n = 50). The survival rates of stages pT2, pT3 and pT2–3N+ were 87.8, 61.0 and 0%, respectively (p = 0.0462). The survival analysis of grade 1–2 and grade 3–4 tumors revealed 92.3 and 51.5% survival rates, respectively (p = 0.002). The survival rates of mutant p53+ and mutant p53– cases were 33.3 and 84.2%, respectively (p = 0.0027). The logistic regression test analysis demonstrated that tumor grade, tumor stage and mutant p53 positivity status were the most significant prognostic factors (p < 0.03). The survival rates of mutant p53+ and p53– cases at stages pT2, pT3 and pT2–3N+ were 66.67 versus 91.48%, 33.3 versus 71.43% and 0 versus 100%, respectively (p = 0.0392). A similar finding was present at each stage for cellular grades (p = 0.0093). The survival rates of mutant p53+ and p53– cases for grades 3 and 4 were 33.33 and 74.48%, respectively (p = 0.2731). Conclusion: Our results suggested that many parameters can affect survial of RCC cases, but among these, tumor grade, tumor stage and p53 mutation status are the most important prognostic factors, but p53 mutation status and cellular grade can afford additional prognostic information at each stage.
Scrotal Extraperitoneal Hernia of the Ureter: Case Report and Literature Review
Authors: Giglio Matteo , Medica Mauro , Germinale Francesco , Raggio Matteo , Campodonico Fabio , Stubinski Robert , Carmignani Giorgio
Published: April 2003

Ureteral herniation is a rare, often misdiagnosed event and serious surgical complications are possible. Until 1992, 128 cases of ureteral herniation were reported and in 54 (42%) the inguino-scrotal region was involved. From an anatomical and pathogenic standpoint, two types of uretero-inguinal hernias can be identified: paraperitoneal (more frequent, acquired, always presenting a peritoneal hernia sac, frequently associated with other herniated abdominal structures) and extraperitoneal (very uncommon, congenital, never associated with a true peritoneal sac, always composed only of the ureter). We describe a new case of scrotal extraperitoneal ureteral hernia and review the current urological, surgical and radiological literature to analyze the main clinical characteristics of this pathology and its ideal treatment.
Effect of Head-Up Body Tilt Position on Autonomic Function and Cerebral Oxygenation in Preterm Infants
Authors: Schrod Lothar , Walter Julia
Published: April 2003

Skin-to-skin care (kangaroo) of premature infants causes orthostatic stress. Therefore, the effect of head elevated body tilt position (HETP) of 30% following HETP determined by near infrared spectroscopy. After stabilization within several minutes, prolonged tilting did not result in any further significant changes of tHb, heart rate, mean arterial pressure and oxygen saturation measured by pulseoxymetry. Respiratory frequency was reduced by 6–12%. Spectral analysis of heart rate variability revealed a greater increase in low frequency than high frequency activity following HETP reflecting a relative increase in sympathetic versus vagal activation. Only preterm infants ≤1,500 g showed a significant decrease of regional cerebral oxygen saturation (rSO2) of about 2–5% from day 2 to 8. As this mild decrease in rSO2 is clinically insignificant, there were no severe side effects of prolonged tilting in stable preterm infants even during the first days of life. However, the initial decline of tHb might be critical in very immature infants and needs further investigations.
Expression of Transcription Factors in the Brain of Rats with Perinatal Asphyxia
Authors: Lubec B. , Labudova O. , Hoeger H. , Kirchner L. , Lubec G.
Published: April 2003

No information is available on transcription factors (TF), the main regulators of gene expression, in perinatal asphyxia (PA), and as pathomechanisms in PA are different, data on TFs from ischemia or hypoxia cannot be simply extrapolated to PA, and no studies have been reported to show an expressional pattern or the concerted action of TFs. We, therefore, used a gene-hunting technique, subtractive hybridization, to show sequences different in brains of normoxic and perinatally asphyxiated (10 and 20 min of asphyxia) rats. These subtracted sequences were identified by gene bank and assigned to individual genes. At 10 min of PA the TFs NFI/CAAT-binding protein, NF-kappa-B p65, N-myc, basic helix loop helix protein D82868, and c-myc intron binding protein were upregulated. At 20 min of PA the TFs SOX4 and neuronal death factor were upregulated, whereas the TFs c-maf, PEBP major transcription factor, brn-2, homeodomain protein Af004431, and zinc finger transcriptional factor M65008 were downregulated. The biological meaning of our findings is the demonstration of a pathophysiological pattern of TFs including POU, zinc finger, homeodomain, and basic helix-loop helix motifs in PA, proposing pathomechanisms for brain damage from PA, explaining transcriptional changes in general (as, e.g., NF-kappa-B p65, etc.) or in specific terms (as, e.g., neuronal death factor).
The murine atrial myosin light chain-2 gene:a member of an evolutionarily conserved family of contractile proteins
Authors: Doevendans P.A. , Bronsaer R. , Lozano P.R. , Kubalak S. , van Bilsen M.
Published: April 2003

Recently the near complete cDNA of the regulatory atrial myosin light chain (MLC-2a) was cloned. The atrial specific isoform has been shown to be a useful molecular marker for cardiac chamber specification. Therefore, the regulatory sequence of the gene will provide clues on cardiomyocyte differentiation and atrial specific transcription regulation. Here we report the identification of the murine genomic sequence of the MLC-2a gene (Mylc2a). The entire 5′ flanking region was identified and sequenced. In addition, the exon-intron boundaries and 3′ flanking region were determined. Sequence comparison revealed the presence of the final exon (11) of the mouse glucokinase gene on chromosome 11, 2.0 kb upstream of the Mylc2a transcription start site. In addition, we compared the structure of the gene to other myosin light chains to show evolutionary conservation. The intron-exon boundaries turned out to be highly conserved and an increasing intron size in more complex mammalian species was found. At the amino acid level there is 95% homology between the human and mouse MLC-2a sequence.
Isolation, characterization and mapping of the mouse and human PRG4 (proteoglycan 4) genes
Authors: Ikegawa S. , Sano M. , Koshizuka Y. , Nakamura Y.
Published: April 2003

PRG4 (proteoglycan 4) has been identified as megakaryocyte stimulating factor and articular superficial zone protein. PRG4 has characteristic motifs including somatomedin B and hemopexin domains, a chondroitin sulfate-attachment site and mucin-like repeats. During a screen of genes implicated in ectopic ossification, we found a novel mouse gene highly homologous to human and bovine PRG4 genes. Here, we report isolation, characterization and mapping of the gene, Prg4 together with characterization of its human orthologue. Prg4 cDNA was 3,320 bp long, encoding a 1,054 amino-acid protein. Human and mouse PRG4 genes each consisting of 12 exons spanned 18 and 16 kb, respectively. Characteristic motifs were conserved across species; however, the mucin-like repeat regions were highly diverse in length between species with a tendency that larger animals had longer repeats. Expression of human and mouse PRG4 genes was similar and found not only in cartilage, but also in liver, heart, lung, and bone. Expression of the mouse gene increased with progression of ectopic ossification. Multiple tissue-specific splicing variants lacking some of the motifs were found in both human and mouse. Although a specific role in the articular joint has previously been reported, the presence of multi-functional motifs as well as unique expression and alternative splicing patterns suggest that PRG4 functions in several distinctive biological process including regulation of ossification.
Gamete segregation in female carriers of Robertsonian translocations
Authors: Munné S. , Escudero T. , Sandalinas M. , Sable D. , Cohen J.
Published: April 2003

Eleven female carriers of either 45,XX,der(13;14) (q10;q10) or 45,XX,der(14;21)(q10;q10) underwent hormonal stimulation with the purpose of producing enough oocytes for in-vitro fertilization and preimplantation genetic diagnosis. Polar body biopsy was performed in those oocytes and FISH with painting probes was applied in their metaphase-like first polar body chromosomes. In this way, unbalanced, normal and balanced oocytes could be distinguished and segregation modes ascertained. der(14;21)(q10;q10) produced 42% unbalanced, 37% normal and 21% balanced oocytes (n = 86) while der(13;14)(q10;q10) generated 33% unbalanced, 51% normal and 16% balanced oocytes (n = 69). In both translocations the number of normal oocytes was significantly higher than the number of balanced oocytes. However, while the frequency of unbalanced events involving chromosome 13 and 14 was similar in der(13;14)(q10;q10), there were significantly more abnormalities involving chromosome 21 than 14 in the der(14;21) (q10;q10) cases. When comparing survival rates to term, trisomies from Robertsonian origin seem to survive more often than those originated by non-disjunction in non-translocation carriers. The meiotic segregation patterns found in female Robertsonian translocations are different from those described in male carriers, with higher rates of unbalanced gametes in females than in males.
Localization by FISH of the 31 Texas nomenclature type I markers to both Q- and R-banded bovine chromosomes
Authors: Hayes H. , Di Meo G.P. , Gautier M. , Laurent P. , Eggen A. , Iannuzzi L.
Published: April 2003

A series of 31 marker genes (one per chromosome) were localized precisely to both Q- and R-banded bovine chromosomes by fluorescence in situ hybridization (FISH), as a contribution to the revised chromosome nomenclature of the three major domestic bovidae (cattle, sheep and goat). All marker genes except one (LDHA) are taken from the Texas Nomenclature of the cattle karyotype published in 1996. Homologous probes for each marker gene were obtained by screening a bovine BAC library by PCR with specific primer pairs. After labeling with biotin, each probe preparation was divided into two fractions and hybridized to bovine chromosomes identified either by Q or R banding. Clear signals and good quality band patterns were observed in all cases. Results of the two series of hybridizations are totally concordant both for Q and R band chromosome numbering and precise band localization. This work permits an unambiguous correlation between the Q/G- and R-banded 31 bovine chromosomes, including chromosomes 25, 27 and 29 which remained unresolved in the Texas Nomenclature (1996). Hybridization of the chromosome 29 marker gene to metaphase spreads from a 1;29 Robertsonian translocation bull carrier showed a positive signal on the short arm of this rearranged chromosome, confirming that the numbering of this long-known translocation in cattle is correct when referring to the Texas Nomenclature (1996). Taking into account that cattle, goat and sheep have very similar banded karyotypes, the data presented here will help to establish a definite and complete reference chromosome nomenclature for these species.
Isolation and characterization of a novel human gene, NIF3L1, and its mouse ortholog, Nif3l1, highly conserved from bacteria to mammals
Authors: Tascou S. , Uedelhoven J. , Dixkens C. , Nayernia K. , Engel W. , Burfeind P.
Published: April 2003

We report the cloning and characterization of novel human and murine genes NIF3L1 and Nif3l1 which are strongly homologous to the yeast Ngg1-interacting factor 3 homolog. Mouse Nif3l1 and human NIF3L1 encode predicted proteins of 376 amino acids and 377 amino acids, respectively. Northern blot analysis on RNA from different postnatal murine tissues showed a ubiquitous expression pattern of mouse Nif3l1 with a transcript of approximately 1.85 kb. RT-PCR analysis on prenatal mouse RNA and embryonic stem cell RNA demonstrated expression of Nif3l1 throughout embryonic development. Additionally, expression analysis on cell lines revealed strong overexpression of Nif3l1 in the spermatogonia-derived cell line GC-1 spg and in the teratocarcinoma cell line F9. The mouse gene was mapped to chromosome 1, region C. Human NIF3L1 consists of seven exons spanning 14.5 kb of genomic DNA and is located on chromosome 2q33. A fusion protein consisting of the GFP (green fluorescent protein) and the ORF of human NIF3L1 showed a localization of the predicted protein in the cytoplasm. In the N-terminal and C-terminal region, mouse Nif3l1 and human NIF3L1 are strongly homologous to proteins of other species, e.g. the recently cloned Drosophila symbol=anon-35F/36F gene with 41% amino acid identity and several proteins from yeast including the yeast Ngg1-interacting factor 3 homolog with 46% amino acid identity, the hypothetical protein YGL221c and yeast Ngg1-interacting factor 3 (Nif3) with 37% amino acid identity. Other proteins from lower organisms, e.g a conserved hypothetical protein from Ureaplasma urealyticum or a hypothetical protein SCC30.09c from Streptomyces coelicolor show approximately 25–30% amino acid identity in the two flanking regions of the protein. These similarities indicate a high degree of conservation of mouse Nif3l1 and human NIF3L1 from bacteria to mammals.
Significance of chromosome 5 and 17 changes in the development of carcinoma of the cervix uteri
Authors: Atkin N.B.
Published: April 2003

Two chromosomes that undergo nonrandom changes in carcinoma of the cervix and have been studied for several decades in this laboratory are discussed. The first, chromosome 5, is discussed in view of the frequent appearance of an isochromosome for 5p, often in two or more copies and commonly associated with fewer that the expected number of normal copies of this chromosome. The second is chromosome 17, where a translocation involving another chromosome may result in a 17p+, and the significant change appears to be a loss from 17p that may include the p53 gene (TP53) and/or other tumor-suppressor genes located on this chromosome arm.
Fusion genes in leukemia: an emerging network
Authors: Bohlander S.K.
Published: April 2003

The molecular analysis of recurring chromosome rearrangements, especially of translocations and inversions, has provided us with valuable insight into the pathogenesis of hematological malignancies. Many translocations result in the fusion of genes located at the translocation breakpoints. In recent years we have witnessed a rapid rise in the number of chromosome translocations in leukemias being characterized at the molecular level. However, the number of genes being newly identified as translocation fusion genes has not risen at the same pace. This is due to the fact that several genes are involved in more than one translocation forming fusion genes with a number of other partner genes. Not only does one find star-shaped topologies, with one gene forming fusions with several others (e.g. ETV6/PDGFRB, ETV6/JAK2, ETV6/ABL etc.), but also networks connecting several genes with more than one fusion partner (e.g. ETV6/RUNX1 (AML1), RUNX1/CBFA2T1 (ETO), ETV6/EVI1, RUNX1/EVI1, ETV6/ABL, BCR/ABL). The emergence of such networks with the “recycling” of genes in new fusion combinations suggests that there is a rather limited number of genes which can be altered to cause leukemia.
The species and chromosomal distribution of the centromeric α-satellite I sequence from sheep in the tribe Caprini and other Bovidae
Authors: Chaves R. , Guedes-Pinto H. , Heslop-Harrison J.S. , Schwarzacher T.
Published: April 2003

The evolution of chromosomes in species in the family Bovidae includes fusion and fission of chromosome arms (giving different numbers of acrocentric and metacentric chromosomes with a relatively conserved total number of arms) and evolution in both DNA sequence and copy number of the pericentromeric α-satellite I repetitive DNA sequence. Here, a probe representing the sheep α-satellite I sequence was isolated and hybridized to genomic DNA digests and metaphase chromosomes from various Bovidae species. The probe was highly homologous to the centromeric sequence in all species in the tribe Caprini, including sheep (Ovis aries), goat (Capra hircus) and the aoudad or Barbary sheep (Amnotragus lervia), but showed no detectable hybridization to the α-satellite I sequence present in the tribe Bovini and at most very weak to species in the tribes Hippotragini, Alcelaphini or Aepycerotini. The sex chromosomes of sheep, goat and aoudad did not contain detectable α-satellite I sequence; in sheep, one of the three metacentric autosomal chromosomes does not carry the sequence, while in aoudad, it is essentially absent in three large autosomal pairs as well as the large metacentric chromosome pair. The satellite probes can be used as robust chromosome and karyotype markers of evolution among tribes and increase the resolution of the evolutionary tree at the base of the Artiodactyla.
Cloning and characterization of the breakpoint regions of a chromosome 11;18 translocation in a patient with hamartoma of the retinal pigment epithelium
Authors: Kutsche K. , Glauner E. , Knauf S. , Pomarino A. , Schmidt M. , Schröder B. , Nothwang H.G. , Schüler H.M. , Goecke T.O. , Kersten A.J. , Althaus C. , Gal A.
Published: April 2003

Mutations of various tumor suppressor genes, e.g., PTEN, TSC1, and TSC2, are known to be responsible for different inherited diseases presenting with multiple hamartomas, a benign tumor resembling neoplasia that results from faulty organ development. Combined hamartoma of the retinal pigment epithelium (RPE) and retina is a rare, congenital, focal malformation of the fundus. So far, no disease gene has been associated with this disorder. By molecular analysis of an apparently balanced and reciprocal translocation between the short arms of chromosomes 11 and 18, t(11;18)(p13;p11.31), in a patient with hamartoma of the RPE and retina, we selected PAC clones crossing the breakpoints on both derivative chromosomes 11 and 18. For the overlapping chromosome 11 clone, two EST clusters were identified, suggesting the existence of at least two genes in the breakpoint region. We constructed a PAC contig and showed that at least three exons of a novel gene map to the breakpoint region on chromosome 18. Based on the results of FISH analysis with the PAC clones of this contig, we suggest the occurrence of a complex rearrangement.
Unusual triploid males in a microchromosome-carrying clone of the Amazon molly, Poecilia formosa
Authors: Lamatsch D.K. , Nanda I. , Epplen J.T. , Schmid M. , Schartl M.
Published: April 2003

The Amazon molly, Poecilia formosa, is an all-female fish of hybrid origin which reproduces by gynogenesis, i.e. it depends on sperm of males of closely related species to trigger parthenogenetic development of the embryo. Therefore the offspring is clonal and identical to the mother. In rare cases the exclusion mechanism fails and paternal introgression occurs. This may result either in triploid offspring – if the whole haploid chromosome set of the sperm fuses with the diploid egg nucleus – or in siblings with microchromosomes – if only subgenomic amounts of paternal DNA are included. In one of our diploid, microchromosome-carrying laboratory stocks we observed eight triploid individuals which all developed into males. We investigated the mitotic and meiotic chromosomes, the synaptonemal complex (SC), and sperm production of these males, and compared them to males of the gonochoristic parental species (P. latipinna and P. mexicana) and their hybrids. This comparison revealed that P. formosa males are functional males with reduced effective fertility. They show a deviation from the typical 23 bivalents in the synaptonemal complexes as well as in diakinesis due to the triploid state. They produced offspring but only with gynogenetic Amazon molly females. This shows that the probably aneuploid sperm from P. formosa males can trigger parthenogenetic development of unreduced eggs.
Prenatal molecular cytogenetic diagnosis of partial tetrasomy 10p due to neocentromere formation in an inversion duplication analphoid marker chromosome
Authors: Levy B. , Papenhausen P.R. , Tepperberg J.H. , Dunn T.M. , Fallet S. , Magid M.S. , Kardon N.B. , Hirschhorn K. , Warburton P.E.
Published: April 2003

Neocentromeres are fully functional centromeres found on rearranged or marker chromosomes that have separated from endogenous centromeres. Neocentromeres often result in partial tri- or tetrasomy because their formation confers mitotic stability to acentric chromosome fragments that would normally be lost. We describe the prenatal identification and characterization of a de novo supernumerary marker chromosome (SMC) containing a neocentromere in a 20-wk fetus by the combined use of comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH). GTG-banding of fetal metaphases revealed a 47,XY,+mar karyotype in 100% of cultured amniocytes; parental karyotypes were both normal. Although sequential tricolor FISH using chromosome-specific painting probes identified a chromosome 10 origin of the marker, a complete panel of chromosome-specific centromeric satellite DNA probes failed to hybridize to any portion of the marker. The presence of a neocentromere on the marker chromosome was confirmed by the absence of hybridization of an all-human-centromere alpha-satellite DNA probe, which hybridizes to all normal centromeres, and the presence of centromere protein (CENP)-C, which is associated specifically with active kinetochores. Based on CGH analysis and FISH with a chromosome 10p subtelomeric probe, the marker was found to be an inversion duplication of the distal portion of chromosome 10p. Thus, the proband’s karyotype was 47,XY,+inv dup(10)(pter→p14∼15::p14∼15→neo→pter), which is the first report of partial tetrasomy 10p resulting from an analphoid marker chromosome with a neocentromere. This study illustrates the use of several molecular strategies in distinguishing centric alphoid markers from neocentric analphoid markers.
Alternative splicing, chromosome assignment and subcellular localization of the testicular haploid expressed gene (THEG)
Authors: Mannan A. , Lücke K. , Dixkens C. , Neesen J. , Kämper M. , Engel W. , Burfeind P.
Published: April 2003

We have previously isolated and characterized the mouse Testicular Haploid Expressed Gene (Theg) that is specifically expressed in haploid germ cells. We now describe the molecular cloning and characterization of the human homologue (THEG) of mouse Theg. Expression studies by using both dot blot and Northern blot techniques revealed that human THEG is expressed specifically in the testis. Additionally, we found two alternatively spliced transcripts (THEG major and THEG minor) for THEG by using reverse transcription-polymerase chain reaction on human testicular RNA. Sequence analysis of these PCR products demonstrated that the smaller transcript (THEG minor) lacks 72 bp which was also observed for the mouse Theg. We have isolated the cDNAs of human THEG major and THEG minor, containing the complete open reading frames, which encode putative nuclear proteins of 379 amino acids and 355 amino acids, respectively. Database searches identified two genomic clones on chromosome 19 harboring the human THEG gene, which is approximately 14 kb pairs in size, contains eight exons, and comparison of the two cDNA sequences with the genomic sequence indicated that the smaller transcript lacks exon 3. Furthermore, we assigned the human THEG gene (THEG) to human chromosome 19ptel→ p13 by fluorescence in situ hybridization. Moreover, we detected mouse THEG protein prominently in the nucleus of round spermatids by using an antibody against THEG on both testicular sections and cellular suspensions. Additionally, the subcellular localization of mouse THEG was confirmed by a green fluorescent protein (GFP) fusion protein of mouse THEG which was found mainly in the nucleus of transfected NIH3T3 cells. These data suggest that both human and mouse THEG are specifically expressed in the nucleus of haploid male germ cells and are involved in the regulation of nuclear functions.
A distinctive phenotype associated with an interstitial deletion 6q14 contained within a de novo pericentric inversion 6 (p11.2q15)
Authors: Passarge E.
Published: April 2003

This report describes a nearly 25-year-old female with an interstitial deletion of band 14 in the long arm of one chromosome 6 (6q14). The deletion is contained within a de novo pericentric inversion with breakpoints in 6p11.2 and 6q15 (Karyotype 46,XX, del(6)(q13q15),inv(6)(p11.2q15). The distal breakpoint of the deletion and the pericentric inversion at 6q15 are the same, but the proximal breakpoints differ. Since cells with other chromosomal findings were not detected in cultured lymphocytes and fibroblasts, chromosome mosaicism seems unlikely. Thus, it is assumed that the inversion and the deletion originated from the same event. The development of a distinctive phenotype in the patient was observed over a period of 22 years. It includes characteristic dysmorphic facial features such as ocular hypertelorism, flat nasal bridge, prominent zygomatic bones, and a depressed glabella. A striking, non-progressive deficit of motor control is manifest in an inability to use her hands properly and a broad-based slow-motion-like gait. Although severely deficient in abstract mental abilities and speech development, she is well adapted to family life and to a school for retarded individuals. Normal height and head circumference, and reduced sensitivity to pain are noteworthy. Presumably the deletion caused the phenotype and the distinct behavioral pattern. This patient probably represents a novel chromosomal phenotype that results from aggregate haploinsufficiency of gene loci in the deleted region.
An SRY-negative 47,XXY mother and daughter
Authors: Röttger S. , Schiebel K. , Senger G. , Ebner S. , Schempp W. , Scherer G.
Published: April 2003

Females with XY gonadal dysgenesis are sterile, due to degeneration of the initially present ovaries into nonfunctional streak gonads. Some of these sex-reversal cases can be attributed to mutation or deletion of the SRY gene. We now describe an SRY-deleted 47,XXY female who has one son and two daughters, and one of her daughters has the same 47,XXY karyotype. PCR and FISH analysis revealed that the mother carries a structurally altered Y chromosome that most likely resulted from an aberrant X-Y interchange between the closely related genomic regions surrounding the gene pair PRKX and PRKY on Xp22.3 and Yp11.2, respectively. As a consequence, Yp material, including SRY, has been replaced by terminal Xp sequences up to the PRKX gene. The fertility of the XXY mother can be attributed to the presence of the additional X chromosome that is missing in XY gonadal dysgenesis females. To our knowledge, this is the first human XXY female described who is fertile.
Elevated DNA sequence diversity in the genomic region of the phosphatase PPP2R3L gene in the human pseudoautosomal region
Authors: Schiebel K. , Meder J. , Rump A. , Rosenthal A. , Winkelmann M. , Fischer C. , Bonk T. , Humeny A. , Rappold G.A.
Published: April 2003

The evolution, inheritance and recombination rate of genes located in the pseudoautosomal region 1 (PAR1) is exceptional within the human genome. Pseudoautosomal genes are identical on X and Y chromosomes and are not inherited in a sex linked manner. Due to an obligatory recombination event in male meiosis, pseudoautosomal genes are exchanged frequently between X and Y chromosomes. During the isolation, characterization and sequencing of a novel gene PPP2R3L, which was classified by sequence homology as a novel member of the protein phosphatase regulatory subunit families, it became apparent that cosmids of different origin harboring this gene are highly polymorphic between individuals, both at the nucleotide level and in the number and sequence of tandem repeats.
Molecular evolution of the murine tspy genes
Authors: Schubert S. , Dechend F. , Skawran B. , Krawczak M. , Schmidtke J.
Published: April 2003

Molecular aspects of murine evolution were studied by sequencing, and subsequently comparing, introns of the Y-chromosomal tspy genes from Apodemus agrarius, A. sylvaticus, A. flavicollis, Mus platythrix (subgenus Pyromys), M. booduga (subgenus Leggada), and from species of the subgenus Mus, including M. cervicolor, M. macedonicus and M.spretus. Estimates of nucleotide substitution rates in these lineages were in perfect agreement with phylogenetic data previously published by She et al. (1990), Catzeflis et al. (1992; 1993), and Lyon et al. (1996). The only exception was provided by a comparatively late divergence of M. spretus and M. macedonicus. Our data also suggest that M.booduga diverged from the subgenus Mus about 3 Myr ago.
Cloning of the 18S rDNA gene, an internal transcribed spacer, and the 5′ region of the 28S rDNA gene of Cope’s gray treefrog, Hyla chrysoscelis
Authors: Owens Jr G. , Wiley J.E.
Published: April 2003

The location of rDNA genes on the chromosomes of most species is identical within that species, usually occurring on the same chromosome or chromosomes. This is not the case in Cope’s gray treefrog, Hyla chrysoscelis, where the rDNA genes are polymorphic for chromosome location. The occasions leading to this polymorphism have yet to be determined. The first step in understanding the nature of the polymorphism is the characterization of the ribosomal gene array. Here we describe the cloning, sequencing, and confirmation, by fluorescence in situ hybridization, of the 18S rDNA gene, a region which includes the end of the 18S rDNA gene, an internal transcribed spacer, and a portion of the 5′ end of the 28S rDNA gene in H. chrysoscelis.
Microsatellite instability
Authors: Atkin N.B.
Published: April 2003

Unlike aneuploidy, considered to be the cardinal feature of malignant tumors ever since the chromosomal analysis of neoplastic cells became technically feasible, a second pathway toward malignancy has emerged over the past decade that is not characterized by gross aneuploidy but, instead, by inactivation of the DNA mismatch repair system, leading to a hypermutable state in which simple repetitive DNA sequences are unstable during DNA replication. Although mutations of many of these microsatellite sequences are presumably innocuous, because they do not occur in the coding or regulatory regions of genes, other such sequences are critically located in the coding regions of genes involved in the regulation of cell growth. First discovered in the rather uncommon hereditary nonpolyposis colorectal cancer syndrome, where there is an inactivating germline mutation in one of the DNA mismatch repair genes and most of the tumors show microsatellite instability, the latter phenomenon has since been implicated in about 15% of sporadic colorectal cancers, as well as in cancers at several other sites, such as the endometrium. Tumors showing microsatellite instability are generally near-diploid, are at a low stage of development, have a favorable prognosis, and, in the colon, are commonly located on the right side. In recent years, epigenetic phenomena, including hypermethylation and loss of imprinting, have come to be recognized as having a significant bearing on the development of these tumors.
A novel member of the STOMATIN/EPB72/mec-2 family, stomatin-like 2 (STOML2), is ubiquitously expressed and localizes to HSA chromosome 9p13.1
Authors: Owczarek C.M. , Treutlein H.R. , Portbury K.J. , Gulluyan L.M. , Kola I. , Hertzog P.J.
Published: April 2003

A cDNA encoding a novel second member of the Band7/stomatin-like/SPFH domain family in humans designated stomatin-like 2 (STOML2) has been isolated using the technique of cDNA Representational Difference Analysis. The STOML2 cDNA encoded a 356 amino acid residue polypeptide with a predicted molecular weight of 38.5 kDa. The predicted polypeptide sequence of STOML2 could be delineated into three major domains: an N-terminal α-helical region; a domain with significant similarity to a 172 amino acid region of the HSA stomatin polypeptide, composed of an alternating α-helical and β-sheet structure and a C-terminal domain that was mostly α-helical. The stomatin-like domain was observed in 51 other proteins with potentially diverse functions. Based on its homology to stomatin, STOML2 was predicted to be cytoplasmically located. However, unlike most of the other proteins containing stomatin-like domains, the predicted STOML2 polypeptide does not contain a transmembrane region although the presence of N-myristoylation sites suggest that it has the potential to be membrane-associated. Northern blot analysis of a panel of poly(A)+ mRNA from normal human adult tissues showed that a single 1.3-kb mRNA transcript encoding STOML2 was ubiquitously expressed, with relatively higher levels in skeletal muscle and heart compared to other tissues. Comparison of the STOML2 cDNA sequence with human genomic DNA indicated that the gene encoding STOML2 was 3,250 bp long and consisted of ten exons interrupted by nine introns. We have mapped STOML2 to HSA chromosome 9p13.1, a region that is rearranged in some cancers and thought to contain the gene responsible for acromesomelic dysplasia.
Refined localization of twenty-one genes in subregion p13.1 of human chromosome 1
Authors: Chelala C. , Imbeaud S. , Devignes M.-D. , Zoorob R. , Auffray C.
Published: April 2003

In this report, we describe a refinement of the human transcript map of chromosome 1p13.1, a subregion undergoing many aberrations in various types of human cancers. Publicly available genetic linkage, radiation hybrid and physical maps, as well as cytogenetic and sequence data were used to establish the relative order and orientation of ten known intragenic markers. The complete sequence of genomic clones of the region, available at the Sanger Centre, provided the tool for further studies performed by BLAST analysis against all cDNA sequences registered in the Genexpress Index2. This allowed us to assign to subband 1p13.1 nine of the ten known genes, an additional member of the gene family of one of these genes and eleven new transcripts. The remaining known gene and one additional new transcript map at the 1p13.1 and 1p13.2 boundary. The corresponding genes may be responsible for disorders related to this region. The resulting transcript map of 1p13.1 is presented in the printed article with additional data available on a dedicated Web site at the address http://idefix.upr420.vjf.cnrs.fr/CARTO
Genomic organization and refined mapping of the human nuclear corepressor 2 (NCOR2)/ silencing mediator of retinoid and thyroid hormone receptor (SMRT) gene on chromosome 12q24.3
Authors: Jiang Q. , Galiègue-Zouitina S. , Roumier C. , Hildebrand M.P. , Thomas S. , Coignet L.J.
Published: April 2003

The human nuclear co-repressor 2 (N-CoR2) gene (NCOR2, previously called silencing mediator for retinoid and thyroid hormone receptor SMRT) is recruited to nuclear and non-nuclear receptors in a large repressing complex containing also N-CoR1, mSin3 and HDACs. This large complex represses transcription in absence of ligand. Herein we report the high- resolution and refined mapping of NCOR2 at the boundary of sub-bands 12q24.23 and 12q24.31, and its intron/exon structure. The gene contains 45 exons. This information should allow further study of potential NCOR2 genomic alteration in some subsets of malignancies.
Molecular cytogenetic analysis of the highly repetitive DNA in the genome of Apodemus argenteus, with comments on the phylogenetic relationships in the genus Apodemus
Authors: Fukushi D. , Kuro-o M. , Shichiri M. , Obara Y. , Tsuchiya K.
Published: April 2003

The DNA of Apodemus argenteus was digested with DraI, and the resultant DraI fragment of highly repetitive DNA was isolated and analyzed by DNA filter hybridization, cloning, sequencing, and fluorescence in situ hybridization (FISH). Southern blot hybridization and nucleotide sequencing revealed that most of the DraI fragment consisted of a 230-bp repeating unit and contained no sex-chromosome-specific nucleotide sequences. The DraI fragment included the CENP-B box-like sequence, with a strong homology to the human CENP-B box sequence. FISH revealed that the DraI fragment was specific to all pericentromeric C-band-positive regions, as well as to the C-block of the X chromosome. No hybridization signals were obtained from A. speciosus, A. peninsulae peninsulae, A.p. giliacus, A. agrarius, A. sylvaticus, A. semotus, or Musmusculus when the DraI fragment was used as probe. Peptide nucleic acid (PNA)-FISH using the CENP-B box-like sequence in the DraI fragments as probe suggested that this nucleotide sequence was also specific to all pericentromeric C-heterochromatic regions of A. argenteus chromosomes. Zoo-blot hybridization using DraI-digested genomic DNA from three species of Apodemus (namely, A. argenteus, A. speciosus, and A. peninsulae) and from Mus musculus strongly suggested that the consensus DraI fragment contained nucleotide sequences that were species-specific for A. argenteus. These results also suggest that A. argenteus is phylogenetically distant from other Apodemus species examined, as well as the possibility that the DraI fragment might be related directly to the delayed quinacrine mustard fluorescence of many pericentromeric C-heterochromatic regions of the chromosomes in A. argenteus.
Comparative analysis of the promoter structure and genomic organization of the human and mouse ABCA7 gene encoding a novel ABCA transporter
Authors: Broccardo C. , Osorio J. , Luciani M.-F. , Schriml L.M. , Prades C. , Shulenin S. , Arnould I. , Naudin L. , Lafargue C. , Rosier M. , Jordan B. , Mattei M.G. , Dean M. , Denèfle P. , Chimini G.
Published: April 2003

We report here the genomic and transcriptional characterization in mouse and man of a novel transporter of the ABCA subclass, named ABCA7. As it is the case for other ABCA genes, the predicted protein encoded by ABCA7 is a full symmetric transporter, highly conserved across species. The ABCA7 gene maps to human chromosome 19 and to the homologous region at band B4-C1 on mouse chromosome 10. The preferential expression of ABCA7 in the spleen, thymus, and fetal liver is consistent with the finding, in both human and mouse promoter, of sites targeted by lymphomyeloid-specific transcription factors. This suggests that ABCA7 may play a pivotal role in the developmental specification of hematopoietic cell lineages.