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PubMedDate not supplied

Automatic segmentation of non-enhancing brain tumors in magnetic resonance images.

Tumor segmentation from magnetic resonance (MR) images may aid in tumor treatment by tracking the progress of tumor growth and/or shrinkage. In this paper we present the first automatic segmentation method which separates non-enhancing brain tumors from healthy tissues in MR images to aid in the task of tracking tumor size over time. The MR feature images used for the segmentation consist of three weighted images (T1, T2 and proton density (PD)) for each axial slice through the head. An initial segmentation is computed using an unsupervised fuzzy clustering algorithm. Then, integrated domain knowledge and image processing techniques contribute to the final tumor segmentation. They are applied under the control of a knowledge-based system. The system knowledge was acquired by training on two patient volumes (14 images). Testing has shown successful tumor segmentations on four patient volumes (31 images). Our results show that we detected all six non-enhancing brain tumors, located tumor tissue in 35 of the 36 ground truth (radiologist labeled) slices containing tumor and successfully separated tumor regions from physically connected CSF regions in all the nine slices. Quantitative measurements are promising as correspondence ratios between ground truth and segmented tumor regions ranged between 0.368 and 0.871 per volume, with percent match ranging between 0.530 and 0.909 per volume.

Astrocytoma↗
PubMed1992

Intra-arterial thrombin activity produced by percutaneous transluminal angioplasty eliminated by segmentally enclosed thrombolysis.

We determined the specific marker of thrombin activity, fibrinopeptide A (FPA), in the vicinity of dilated sites during percutaneous transluminal angioplasty (PTA) for femoro-popliteal obstructions in 24 patients. Blood samples were drawn proximal to dilated segments from a 4F catheter inserted retrogradely in the common femoral artery and distal to dilated segments from the balloon catheter tip. Median +/- S.E. FPA concentration was 21.5 +/- 4.4ng ml-1 before PTA. Immediately after dilatation, FPA concentrations were increased to 970.0 +/- 836.9 ng ml-1 distal to dilated segments (p less than 0.00005) and to 48.5 +/- 11.4 ng ml-1 proximally (p less than 0.003). Segmentally enclosed thrombolysis (SET) was undertaken immediately after PTA, when a double balloon catheter was positioned with a balloon at each end of dilated segments. Both balloons were inflated and 5 mg recombinant tissue plasminogen activator (rt-PA) and 1000 IU heparin were enclosed in the segments for 30 min. Immediately after SET, FPA concentration distal to dilated segments was 34.0 +/- 14.2 ng ml-1 and not different from proximal concentrations found after PTA (p = 0.57). Intense fibrinolysis was indicated by significantly increased levels of cross-linked fibrin degradation products (D-dimer) for hours after SET, but FPA concentrations in peripheral blood remained near baseline values. This finding differed from increased thrombin activity found by others during systemic thrombolytic therapy. Early rethrombosis did not occur after PTA in this study.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1996

A comparison of the endobronchial segment of modern left-sided double-lumen tubes in anesthesia for bilateral sequential lung transplantation.

OBJECTIVE: To compare a range of currently available left-sided double-lumen endotracheal tubes (DLTs) in order to demonstrate differences among them with respect to the length of the endobronchial segment. It is proposed that a tube with a short endobronchial segment is better suited to anesthesia under the conditions imposed by double sequential lung transplantation. SETTING: A university hospital with a large heart and lung transplant unit. PARTICIPANTS: The DLTs included in the study were Sher-I-Bronch (Sheridan of Kendall Australia, North Ryde, Sydney, Australia); BronchoCath and BronchoCath II (Mallinckrodt Medical, St Louis, MO); Rüsch single use (Rüsch, Wailbilngen, Germany); Portex single use (Portex, Keen, NH); and Phoenix single-use Robertshaw (Promedica, Preston, Lancashire, UK). MEASUREMENTS AND MAIN RESULTS: The endobronchial segment was measured as the distance from the point of inflation of the bronchial cuff to the tip of the tube. This distance was measured for each manufactured brand in a range of tubes and the mean obtained. The DLTs were compared to assess variability within the brand, and the influence of size on the endobronchial segment. All brands were then compared. Variability within brands is consistent with manufacturer's specified range of +/- 1 to 3 mm. The endobronchial segment increases with size for Rusch and Phoenix DLTs as a design feature. The average lengths of the endobronchial segments are Rusch 23 +/- 2 mm (sizes 35/37) and 25 +/- 2 mm (sizes 39/41); Mallinckrodt 30 +/- 3 mm (BronchoCath) and 31 +/- 3 mm (BronchoCath II); Portex 35 +/- 2 mm; Sheridan 35 +/- 2 mm; Phoenix 47 mm (small), 52 mm (medium), and 56 mm (large). CONCLUSIONS: There exists marked variability in the length of the endobronchial segment of left-sided double-lumen tubes currently available. These differences may be significant in anesthesia for bilateral sequential lung transplantation.

Anesthesia↗
PubMed1997

Limited intentional normovolemic hemodilution: ST-segment changes and use of homologous blood products in patients with left main coronary artery stenosis.

OBJECTIVE: To assess and compare the effects of limited intentional normovolemic hemodilution (LINH) on ST-segment changes and to evaluate the need for homologous blood products. DESIGN: Prospective, randomized study. SETTING: University hospital. PARTICIPANTS: Seventy-one patients with left main stenosis scheduled for semi-urgent coronary artery bypass grafting. INTERVENTIONS: Patients in group A (n = 39) underwent LINH during the prebypass period until a hematocrit of 34% was obtained. Simultaneously, succinyl-linked gelatin was infused. In group B (n = 32), no hemodilution was performed. Mean arterial pressure and central venous pressure were kept as constant as possible. During the postbypass period, autologous blood was retransfused. The need for homologous blood products was noted intraoperatively and postoperatively. MEASUREMENTS AND MAIN RESULTS: ST-segment analysis of lead II and chest lead was continuously performed in all patients. An ST-segment change was defined as a decrease from baseline of 1.0 mm (-0.1 mV). The appearance and degree of ST-segment depression were comparable in both groups (group A: 7 patients -0.1 mV, 1 patient -0.2 mV; group B: 5 patients -0.1 mV; 3 patients -0.2 mV). In group A, ST-segment depression occurred during and after the blood exchange. However, the mean duration of the ST-segment depression (group A: 33 +/- 18 minutes; group B: 20 +/- 10 minutes) was comparable between groups. In group A, a mean of 750 mL +/- 245 mL of blood was obtained. Total blood loss was significantly higher in group B (p < 0.052); 25 patients in group A (64%) and 12 patients in group B (38%) did not require homologous blood products (p < 0.03). Intraoperatively, only the need for packed red cells was greater in group B (p < 0.04). Postoperatively, the use of homologous blood products is higher than intraoperatively (p < 0.02). CONCLUSIONS: LINH performed in patients with left main stenosis, scheduled for semi-urgent coronary bypass, is not associated with increases in frequency, degree, or duration of ST-segment changes. This procedure allowed a reduction in the number of patients who received homologous blood products.

Aged↗
PubMed2003

Automated lung segmentation in X-ray computed tomography: development and evaluation of a heuristic threshold-based scheme.

RATIONALE AND OBJECTIVES: To develop and evaluate a reliable, fully-automated lung segmentation scheme for application in X-ray computed tomography. MATERIALS AND METHODS: The automated scheme was heuristically developed using a slice-based, pixel-value threshold and two sets of classification rules. Features used in the rules include size, circularity, and location. The segmentation scheme operates slice-by-slice and performs three key operations: (1) image preprocessing to remove background pixels, (2) computation and application of a pixel-value threshold to identify lung tissue, and (3) refinement of the initial segmented regions to prune incorrectly detected airways and separate fused right and left lungs. RESULTS: The performance of the automated segmentation scheme was evaluated using 101 computed tomography cases (91 thick slice, 10 thin slice scans). The 91 thick cases were pre- and post-surgery from 50 patients and were not independent. The automated scheme successfully segmented 94.0% of the 2,969 thick slice images and 97.6% of the 1,161 thin slice images. The mean difference of the total lung volumes calculated by the automated scheme and functional residual capacity plus 60% inspiratory capacity was -24.7 +/- 508.1 mL. The mean differences of the total lung volumes calculated by the automated scheme and an established, commonly used semi-automated scheme were 95.2 +/- 52.5 mL and -27.7 +/- 66.9 mL for the thick and thin slice cases, respectively. CONCLUSION: This simple, fully-automated lung segmentation scheme provides an objective tool to facilitate lung segmentation from computed tomography scans.

Image Processing, Computer-Assisted↗
PubMed2004

Statistical validation of image segmentation quality based on a spatial overlap index.

RATIONALE AND OBJECTIVES: To examine a statistical validation method based on the spatial overlap between two sets of segmentations of the same anatomy. MATERIALS AND METHODS: The Dice similarity coefficient (DSC) was used as a statistical validation metric to evaluate the performance of both the reproducibility of manual segmentations and the spatial overlap accuracy of automated probabilistic fractional segmentation of MR images, illustrated on two clinical examples. Example 1: 10 consecutive cases of prostate brachytherapy patients underwent both preoperative 1.5T and intraoperative 0.5T MR imaging. For each case, 5 repeated manual segmentations of the prostate peripheral zone were performed separately on preoperative and on intraoperative images. Example 2: A semi-automated probabilistic fractional segmentation algorithm was applied to MR imaging of 9 cases with 3 types of brain tumors. DSC values were computed and logit-transformed values were compared in the mean with the analysis of variance (ANOVA). RESULTS: Example 1: The mean DSCs of 0.883 (range, 0.876-0.893) with 1.5T preoperative MRI and 0.838 (range, 0.819-0.852) with 0.5T intraoperative MRI (P < .001) were within and at the margin of the range of good reproducibility, respectively. Example 2: Wide ranges of DSC were observed in brain tumor segmentations: Meningiomas (0.519-0.893), astrocytomas (0.487-0.972), and other mixed gliomas (0.490-0.899). CONCLUSION: The DSC value is a simple and useful summary measure of spatial overlap, which can be applied to studies of reproducibility and accuracy in image segmentation. We observed generally satisfactory but variable validation results in two clinical applications. This metric may be adapted for similar validation tasks.

Analysis of Variance↗
PubMed1998

Real-time interactive three-dimensional segmentation.

RATIONALE AND OBJECTIVES: The authors developed a real-time, interactive three-dimensional (3D) segmentation pipeline that uses relatively low-level segmentation operations and provides two-dimensional and 3D visualization through a user-friendly graphical interface. MATERIALS AND METHODS: The low-level segmentation processes were implemented on a massively parallel computer; the graphical user interface was written with a public domain software toolkit. Since their implementation 2 years ago, these segmentation tools have been applied to approximately 300 computed tomographic and magnetic resonance imaging data sets. Two typical clinical cases are presented to demonstrate their applications. RESULTS: The entire processing pipeline can be executed in a few seconds. The tools are simple to learn because they involve the use of low-level procedures and a user-friendly graphical interface with a short interactive response time. Segmentation of the bones, aorta, kidneys, and kidney cysts in case 1 could be performed in about 16 minutes. The time needed to segment each organ in case 2 ranged from about 15 minutes for the skin and brain to about 1 minute for the tumor. CONCLUSION: Satisfactory results can be obtained in a relatively short time with the real-time interactive 3D segmentation system. Operation of the system can be easily learned by a wide variety of nonspecialized users with some medical background.

Algorithms↗
PubMed2001

Space-oriented segmentation and 3-dimensional source reconstruction of ictal EEG patterns.

OBJECTIVES: Characterization of the EEG pattern during the early phase of a seizure is crucial for identifying the epileptic focus. The purpose of the present investigation was to evaluate a method that divides ictal EEG activity into segments of relatively constant surface voltage distribution, and to provide a 3-dimensional localization of the activity during the different segments. METHODS: For each timepoint the electrical voltage distribution on the scalp (the voltage map) was determined from the digitized EEG recording. Through a spatial cluster analysis time sequences where the maps did not change much (segments) were identified, and a 3-dimensional source reconstruction of the activity corresponding to the different mean maps was performed using a distributed linear inverse solution algorithm. RESULTS: Segments dominating early in seizure development were identified, and source reconstruction of the EEG activity corresponding to the maps of these segments yielded results which were consistent with the results from invasive recordings. In some cases a sequence of consecutive segments was obtained, which might reflect ictal propagation. CONCLUSIONS: Segmentation of ictal EEG with subsequent 3-dimensional source reconstruction is a useful method to non-invasively determine the initiation and perhaps also the spread of epileptiform activity in patients with epileptic seizures.

Adolescent↗
PubMedDate not supplied

Segmental instrumentation for thoracic and thoracolumbar fractures: prospective analysis of construct survival and five-year follow-up.

BACKGROUND CONTEXT: Segmental instrumentation systems have replaced nonsegmental systems in all areas of spine surgery. Construct patterns for fracture stabilization have been adapted from deformity experience and from biomechanical studies using nonsegmental systems. Few studies have been completed to validate the use of these implants in trauma or to assess their relative strengths and weaknesses. PURPOSE: To substantiate the safety and efficacy of segmental spinal instrumentation used to treat patients with unstable spinal fractures and to identify successful construct strategies and potential pitfalls. STUDY DESIGN: A prospective, longitudinal single cohort study of patients treated with segmental instrumentation for fractures of the spine. Minimum 2-year follow-up. PATIENT SAMPLE: Seventy-five consecutive patients with unstable fractures of the thoracic, thoracolumbar and lumbar vertebrae, admitted to a level 1 trauma center. All patients sustained high-energy injuries: fifty-five (79%) were injured in motor vehicle accidents, 27 (38%) sustained two or more major additional injuries and 39 (56%) had neurological injuries. OUTCOME MEASURES: Perioperative morbidity and mortality, blood loss, surgical time; postoperative recovery, neurological recovery, complications, thromboembolic and pulmonary disease; long-term outcome measures of fusion, sagittal spinal alignment, construct survival, patient pain and function measures, and return to work and activity. METHODS: A longitudinal, prospective study of surgical outcome after segmental spinal instrumentation. Multifactorial assessment was carried out at prescribed intervals to a mean follow-up of 5 years (range, 2 to 8 years) from the time of surgery. Seventy patients were included in the final analysis. There were 17 thoracic, 36 thoracolumbar and 17 lumbar fractures. RESULTS: At 52 months mean follow-up, 57 of 62 patients (92%) had solid fusion with acceptable spinal alignment. Perioperative complications and mortality were less than expected, based on historical controls matched for injury severity. Rod and hook constructs had 97% good to excellent functional results, with no hardware complications. Six of 11 (55%) patients with short-segment pedicle instrumentation (SSPI) with no anterior column reconstruction had greater than 10 degrees of sagittal collapse during the fracture healing period. Twenty six of 36 neurologically injured patients (72%) experienced (mean) 1.5 Frankel grades recovery after decompression and stabilization. Residual neurological deficit determined return to work: 43 patients (70%) returned to work, 33 without restrictions, 10 with limitations. Five other patients (8%) were fit but unemployed. Fifteen percent experienced some form of hardware failure, but only three (5%) required revision. Hardware complications and fair to poor outcomes occurred after pedicle instrumentation without anterior reconstruction. Patients with anterior reconstruction had 100% construct survival, no sagittal deformity, and less pain. CONCLUSION: Segmental instrumentation allowed immediate mobilization of these severely injured patients, eliminating thromboembolic and pulmonary complications, and reducing overall morbidity and mortality. Segmental instrumentation produced a high rate of fusion with no rod breakage or hook failure. Pedicle screw constructs had a high rate of screw complications associated with anterior column insufficiency, but revision was not always necessary. Eighty percent of these severely injured patients were capable of returning to full-time employment, and 70% did so.

Accidents, Traffic↗
PubMed2004

Regulation of segmental patterning by retinoic acid signaling during Xenopus somitogenesis.

Somites, the segmented building blocks of the vertebrate embryo, arise one by one in a patterning process that passes wavelike along the anteroposterior axis of the presomitic mesoderm (PSM). We have studied this process in Xenopus embryos by analyzing the expression of the bHLH gene, Thylacine1, which is turned on in the PSM as cells mature and segment, in a pattern that marks both segment boundaries and polarity. Here, we show that this segmental gene expression involves a PSM enhancer that is regulated by retinoic acid (RA) signaling at two levels. RA activates Thylacine1 expression in rostral PSM directly. RA also activates Thylacine1 expression in the caudal PSM indirectly by inducing the expression of MKP3, an inhibitor of the FGF signaling pathway. RA signaling is therefore a major contributor to segmental patterning by promoting anterior segmental polarity and by interacting with the FGF signaling pathway to position segmental boundaries.

Animals↗
PubMed1977

Involvement of precursor-specific segments in the in vitro maturation of Bacillus subtilis precursor 5S ribosomal RNA.

In vitro maturation of precursor 5S ribosomal RNA (p5A) from Bacillus subtilis effected by RNase M5 yields mature 5S RNA (m5, 116 nucleotides), and 3' precursor-specific segment (42 nucleotides), and a 5' precursor-specific segment (21 nucleotides) (Sogin, M.L., Pace, B., and Pace, N.R. (1977), J. Biol. Chem. 252, 1350). Limited digestion of p5A with RNase T2 introduces a single scission at position 60 of the molecule; m5 is cleaved at the corresponding nucleotide residue. The complementary "halves" of the molecules could be isolated from denaturing polyacrylamide gels. The isolated fragments of p5A are not substrates for RNase M5, suggesting that some recognition elements can be utilized by RNase M5 only when presented in double-helical form. In exploring the involvement of the precursor-specific segments in the RNase M5-p5A interaction, substrate molecules lacking the 3' or 5' precursor-specific segment were constructed by reannealing complementary "halves" from p5A and m5 RNA. The artificial substrate lacking the 5'-terminal precursor segment was cleaved very much more slowly than the lacking t' segment; the 5' precursor-specific segment therefore contains one or more components recognized by RNase M5 during its interaction with the p5A substrate.

Bacillus subtilis↗
PubMed1996

Coassembly of synthetic segments of shaker K+ channel within phospholipid membranes.

Increasing evidence suggests that membrane-embedded hydrophobic segments can interact within the phospholipid milieu of the membrane with varying degrees of specificity and thus contribute to the folding and oligomerization of proteins. We have used synthetic peptides corresponding to segments from the hydrophobic core of the Shaker potassium channel as a model system to study interactions between membrane-embedded segments. Three synthetic segments of the Shaker K+ channel, comprising the hydrophobic S2, S3, and S4 sequences, were used, and their secondary structure, their interactions with, and orientation within phospholipid membranes were examined. Secondary structure studies revealed that though S3 and S4 both adopt certain fractions of alpha-helical structures in membrane mimetic environments, the alpha-helical content of S3 is lower. Both S3 and S4 bind strongly to zwitterionic phospholipids, with partition coefficients in the order of 10(4) and 10(5) M-1. ATR-FTIR studies showed that while the S4 peptide is oriented parallel to the membrane surface, S3 tends to a more transmembranal orientation. Enzymatic cleavage experiments demonstrated that the presence of S3 induces some change in the proteolytic accessibility of the S4 segment. Resonance energy transfer measurements, done in high lipid/peptide molar ratios, revealed that S3 and S4 cannot self-associate in zwitterionic phospholipid vesicles but can associate with each other and with the S2 segment of the channel. Furthermore, S3 does not interact with the homologous S4 region from the first repeat of the eel sodium channel, demonstrating specificity in the interactions. These results are in line with data indicating that functionally important interactions indeed exist between the negatively charged S2 and S3 regions and the positively charged S4 region [Papazian, D. M., et al (1995) Neuron 14, 1293-1301; Planells-Cases, R., et al. (1994) Proc. Natl. Acad. Sci. U.S.A. 92, 9422-9426]. From a broader point of view, these results provide further support to the notion that interactions (either specific or nonspecific) may exist between transmembrane segments of integral membrane proteins and therefore can contribute to their assembly and organization.

Amino Acid Sequence↗
PubMed2000

Comparison between segmental wall motion and wall thickening in patients with coronary artery disease using quantitative gated SPECT software.

This study was performed to evaluate regional wall motion (WM) and wall thickening (WT) using gated myocardial perfusion single photon emission computed tomography (SPECT) and to determine their similarity and disparity in patients with coronary artery disease (CAD). A total of 44 patients underwent 1 day stress/rest (MIBI) gated SPECT. Commercially available quantitative analysis of gated SPECT (QGS) software was used to generate 3D surface display and cine-mode SPECT display. Left ventricle was divided into nine segments to score WM and WT from 0 (no abnormality) to 4 (severe abnormality) by six independent observers. Finally a mean score was calculated for each segment from the scores of six observers. There was fairly good correlation between WM and WT of individual segments (r = 0.62, p < 0.0001). Concordance rate (IWM - WTI < 1) was 85%. A large difference between WM and WT (WM - WT > or = 2) was observed in 15 segments, including 12 segments with greater WM abnormalities and 3 segments with greater WT abnormalities (lateral and inferior walls). Greater WM abnormalities were most commonly observed in anteroseptal segments especially in post coronary artery bypass grafting (CABG) patients. In conclusion, WM and WT showed similarity on QGS studies. However, these two parameters may be determined separately in gated SPECT studies for comprehensive and robust evaluation of the functional status of myocardium. Analyses based on WM assessment alone may lead to erroneous results especially in septal regions.

Aged↗
PubMed1980

An unusual translocation of immunoglobulin gene segments in variants of the mouse myeloma MPC11.

Immunoglobulin light chain genes of the mouse are composed in germ-line DNA of four separate segments, the leader, V (variable), J (joining) and C (constant) segments. In immunocompetent cells a V and J gene segment are joined by a site-specific recombination event. In variants of the mouse myeloma MPC11 a so-called kappa (k) light chain fragment is expressed which consists of the MOPC321 leader peptide, joined to the kappa constant region peptide. Using the Southern blotting technique we found that the gene coding for the light chain fragment has apkparently been generated by an aberrant translocation of a V gene segment identical or very similar to the MOPC321 V gene segment into the large intervening sequence between the J and the C gene segments. The resulting deletion of the splice signals of the J segments could be the reason for the observed splicing between leader and C region sequences, a phenomenon which may be of general interest for the understanding of the splicing mechanism.

Animals↗
PubMedDate not supplied

Identification of a diversity segment of human T-cell receptor beta-chain, and comparison with the analogous murine element.

The humoral immune system antigen-binding proteins (immunoglobulins) are disulphide-linked heterodimers of light and heavy chains. The gene for the variable region which determines antigen specificity is assembled when one member from each of the dispersed clusters of variable (V) gene segments, diversity (D) elements (for the heavy chains only) and joining (J) segments rearrange and fuse during B-cell development (reviewed in ref. 1). Short recognition sequences adjacent to these elements appear to be involved in the recombination process. The cellular immune system antigen recognition proteins are receptors on the surface of T cells, which are composed of disulphide-linked alpha-chains and beta-chains, each of which has a variable and constant region. Recently, cDNA clones of the beta-chain mRNA have been isolated; the genomic arrangement is very similar to immunoglobulin genes with multiple V beta genes, and two clusters of J beta segments, each of which is upstream from a constant-region gene segment. The V beta and J beta segments have adjacent recombinational recognition sequences like the immunoglobulin elements. However, approximately 10 nucleotides of the cDNA clones between the V beta and J beta regions were not present in the corresponding genomic elements and may have been due to intervening D beta segments. Here we describe a diversity element (D beta 1.1) in a region of high human-mouse homology about 650 bases 5' to the first J beta cluster. Two transcripts which include sequences upstream of D beta 1.1 are found in the human thymus. This region may have some other function besides providing the beta-chain with a diversity segment.

Amino Acid Sequence↗
PubMedDate not supplied

Recombination between an expressed immunoglobulin heavy-chain gene and a germline variable gene segment in a Ly 1+ B-cell lymphoma.

The early stages of murine B-cell differentiation are characterized by a series of immunoglobulin gene rearrangements which are required for the assembly of heavy(H) and light(L)-chain variable regions from germline gene segments. Rearrangement at the heavy-chain locus is initiated first and consists of the joining of a diversity (DH) gene segment to a joining (JH) gene segment. This forms a DJH intermediate to which a variable (VH) gene segment is subsequently added. Light-chain gene rearrangement follows and consists of the joining of a VL gene segment to a JL gene segment: once a productive light-chain gene has been formed the cell initiates synthesis of surface immunoglobulin M (sIgM) receptors (reviewed in ref. 1). These receptors are clonally distributed and may undergo further diversification either by somatic mutation or possibly by continued recombinational events. Such recombinational events have been detected in the Ly 1+ B-cell lymphoma NFS-5, which has been shown to rearrange both lambda and H-chain genes subsequent to the formation of sIgM (mu kappa) molecules. Here we have analysed a rearrangement of the productive allele of NFS-5 and found that it is due to a novel recombination event between VH genes which results in the replacement of most or all of the coding sequence of the initial VHQ52 rearrangement by a germline VH7183 gene. Embedded in the VH coding sequence close to the site of the cross-over is the sequence 5' TACTGTG 3', which is identical to the signal heptamer found 5' of many DH gene segments. This embedded heptamer is conserved in over 70% of known VH genes. We suggest that this heptamer mediates VH gene replacement and may play an important part in the development of the antibody repertoire.

Animals↗
PubMedDate not supplied

Recombination between immunoglobulin variable region gene segments is enhanced by transcription.

Immunoglobulin (Ig) variable (V) region genes are assembled in precursor B (pre-B) lymphocytes from multiple germline segments. The heavy-chain V-region gene is composed of variable (VH), diversity (D) and joining (JH) segments; kappa (K) and lambda (lambda) light-chain V-region genes have analogous VL and JL segments. Assembly of Ig V-gene segments, as well as those of the highly related T-cell receptor, is regulated at several levels and shows both stage and tissue specificity; for example Ig heavy-chain V-gene assembly precedes that of Ig light chains during B-cell differentiation. Joining of all classes of V-gene segments involves conserved recognition sequences that are probably targets for a common recombinase. Evidence has been presented suggesting that rearrangement of specific classes of segments is regulated by modulation of their accessibility to the recombinase. To elucidate mechanisms which control V-region gene assembly, we have investigated the effect of flanking gene expression on the frequency at which introduced V-gene segments are assembled in pre-B cell lines. Our findings suggest that transcription may play a direct role in the regulation of immunoglobulin V-gene assembly.

Animals↗
PubMed1988

Control of neuronal fate by the Drosophila segmentation gene even-skipped.

The central nervous system (CNS) contains a remarkable diversity of cell types. The molecular basis for generating this neuronal diversity is poorly understood. Much is known, however, about the regulatory genes which control segmentation and segment identity during early Drosophila embryogenesis. Interestingly, most of the segmentation and homoeotic genes in Drosophila, as well as many of their vertebrate homologues, are expressed during the development of the nervous system (for example, ref. 3). Are these genes involved in specifying the identity of individual neurons during neurogenesis, just as they specify the identity of cells during segmentation? We previously described the CNS expression of the segmentation gene fushi tarazu (ftz) and showed that ftz CNS expression is involved in the determination of an identified neuron. Here we show that another segmentation gene, even-skipped (eve), is expressed in a different but overlapping subset of neurons. Temperature-sensitive inactivation of the eve protein during neurogenesis alters the fate of two of these neurons. Our results indicate that the nuclear protein products of the eve and ftz segmentation genes are components of the mechanism controlling cell fate during neuronal development.

Animals↗