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PubMed2000

Impact of FK506 and steroids on adaptation after intestinal resection or segmental transplantation.

Segmental small intestinal transplantation (SIT) using living related donors (LRD) is being evaluated as a therapy, clinically. Advantages of this technique include an increase in the donor pool, optimization of the timing of transplants, and potential immunologic benefits. However, the ability of a short segment of intestine to function after transplantation has not been investigated in large animal models. This study evaluates the impact of immunosuppression on the adaptive process and the ability of a transplanted segment of intestine to adapt. A pig model of segmental SIT was used. Animals were resected, leaving 150 cm of distal ileum (n = 5), resected and treated with FK506 (n = 4), or steroids (n = 4), or with FK506 + steroids (n = 7), or transplanted using a similar segment of ileum and treated with FK506 + steroid immunosuppression (n = 9). Animals undergoing resection, or resection plus steroid treatment, did well, gaining weight post-operatively (37% and 15% of preoperative weight, respectively). However, animals undergoing resection and treated with FK506 or FK506 + steroids did poorly, losing weight (-14% and -22% of preoperative weight, respectively) and showing significant impairment of intestinal adaptation, morphologically and functionally. Furthermore, FK506-treated animals developed inflammatory changes in the intestinal mucosa, mimicking rejection. Segmental SIT animals had a high rate of rejection (66%) and showed a similar impairment in adaptation. Hence, segmental SIT is a stringent physiological test of intestinal adaptation. FK506 appears to impair gut function after resection, either directly, or by interfering with the adaptive process. In this model of segmental SIT, FK506 and steroids at the doses tested did not provide adequate immunosuppression to prevent rejection and the graft did not function adequately to allow growth. Further studies are required to evaluate the mechanisms underlying these findings, and to determine if similar effects occur in humans.

Adaptation, Physiological↗
PubMed2000

Comparison of ranked segment analysis (RSA) and cup to disc ratio in computer-assisted optic disc evaluation.

PURPOSE: Ranked segment analysis is a new method for evaluation of optic nerve head topography with the Heidelberg Retina Tomograph. This analysis ranks sector measurements around the optic disc and compares these measurements with rank specific significance limits. We evaluated the diagnostic precision of the ranked segment analysis in a large clinical sample and compared with vertical cup/disc ratio measurements. Vertical cup/disc ratio measurements were not corrected for disc size. METHODS: We analysed optic disc images from 153 normal and 75 glaucomatous eyes using the Heidelberg Retina Tomograph (software version 2.01). Ranked segment analyses and vertical cup/disc ratio measurements were obtained from each optic disc image, and ROC curves were plotted. RESULTS: At the 95% specificity level, sensitivity was significantly lower for ranked segment analysis (70%) compared to vertical cup/disc ratio measurements (85%). Almost 30% of the discs in the glaucoma group were classified as normal using the ranked segment analysis. DISCUSSION: Ranked segment analysis yielded unacceptably poor discrimination, in fact, worse than cup/disc ratio with its known clinical limitations Glaucomatous disc damage typically occurs at the vertical poles of the disc. High rank measurements (low sector values) in normal eyes, on the other hand, are more common in the temporal disc sectors. Important spatial information is lost during the ranking procedure. This may partly explain the low sensitivity of the ranked segment analysis observed in our study. The results raise serious concerns regarding the clinical usefulness of ranked segment analysis.

Adult↗
PubMed2002

Membranes of retinal pigment epithelial cells in vitro are damaged in the phagocytotic process of the photoreceptor outer segment discs peroxidized by ferrous ions.

The ferrous ions released from haemoglobin and storage-transferrin ions cause oxidative stress in the eyes. We observed the phagocytotic process of the photoreceptor outer segment discs peroxidized by ferrous ions in the retinal pigment epithelial (RPE) cells in vitro, and investigated how the ferrous ions influenced RPE in vitro and the photoreceptor outer segment discs. We obtained isolated photoreceptor outer segment discs using sucrose gradient of specific gravity after homogenizing porcine retinas. After bovine RPE cells were cultured with isolated photoreceptor outer segment discs containing FeCl2 for 5 and 24 h, we incubated the specimens with rhodamine phalloidin, antimouse alpha-tubulin antibody and antimouse Ig G (FITC and rhodamine labelled). We observed the specimens by a laser scanning microscopy, and made the ultrathin sections with or without 2% uranyl acetate and 2% lead acetate for examination by transmission electron microscopy. Actin filaments and microtubules of specialized cells such as RPE cells were actively involved in phagocytosis of the photoreceptor outer segment discs. Microtubules were damaged during the phagocytotic process of the photoreceptor outer segment discs peroxidized by ferrous ions. The peroxidation increased the granular and aggregated autofluorescence of the photoreceptor outer segment discs. The membranes of the disc and the phagosomes, and lysosomes in RPE cells were damaged by ferrous ions and had fine particles with high electron density staining without uranium acetate and lead citrate. The cytoskeletons such as actin filaments and microtubules, and the membranes of the phagosomes and the lysosomes in RPE cells in vitro were damaged during the phagocytotic process of the photoreceptor outer segment discs peroxidized by ferrous ions.

Animals↗
PubMed1989

Segment-specific expression of a homoeobox-containing gene in the mouse hindbrain.

The process of segmentation, in which the developing embryo is divided into repetitive structures along its antero-posterior (A-P) axis, as a means of organizing and coordinating the body plan is found in a wide range of organisms. In Drosophila, homoeotic genes are involved in all levels of segmental organization and in determining segment identity. The roles of these genes in segmentation have been found mainly by mutational studies, but also by in situ hybridization, which has shown their domains of expression. In contrast to Drosophila, however, embryonic expression of homoeobox-containing genes in vertebrate organisms has not been found to follow a segmental pattern. Vertebrate segmentation can be clearly seen in the mesodermal somites, but repetitive morphological structures in the central nervous system (neuromeres) have only recently been shown to have developmental significance. Neuromeres in the hindbrain (rhombomeres) have been defined as segmental units by their pattern of nerve formation in the developing chick and by the alternating expression of Krox-20, a gene encoding a zinc-finger DNA-binding protein, in the 9.5-day-old mouse. Here we report that a mouse homoeobox-containing gene, Hox-2.9, is expressed in a segment-specific manner in the developing mouse hindbrain. This expression is in a region which is flanked by the regions of expression of Krox-20, and is precisely contained within a single neuromere, rhombomere 4.

Animals↗
PubMed1993

A Drosophila homologue of human Sp1 is a head-specific segmentation gene.

Segmentation in Drosophila is based on a cascade of hierarchical gene interactions initiated by maternally deposited morphogens that define the spatially restricted domains of gap gene expression at blastoderm (reviewed in ref. 1). Although segmentation of the embryonic head is morphologically obscured, the repeated patterns of expression of the segment polarity genes reflect the formation of seven head segments; two of these depend on the segmentation and homeotic genes used in the trunk, whereas the others form as a result of the activity of the head-specific genes orthodenticle (otd), empty spiracles (ems) and buttonhead (btd). The genes ems and otd encode homeodomain proteins, suggesting that they may function as transcription factors. They are expressed in overlapping stripes in the early embryonic head of Drosophila, and their vertebrate homologues, otx and emx, are expressed in overlapping domains in the anterior central nervous system of the mouse embryo. We show here that btd is expressed in a stripe covering the head analgen of the segments affected in btd lack-of-function mutants and that btd encodes a zinc-finger-type transcription factor with sequence and functional similarity to the prototype mammalian transcription factor Sp1 (ref. 9). When expressed in the spatial pattern of btd, a transgene providing Sp1 activity can support development of the mandibular segment in the head of btd mutant embryos. A ubiquitous transcription factor from humans can therefore replace an essential component of the genetic circuitry required to specify the development of a particular head segment in the fly.

Amino Acid Sequence↗
PubMed1994

Asparagine-linked oligosaccharides are localized to single extracytosolic segments in multi-span membrane glycoproteins.

A comprehensive survey of mammalian multi-span (polytopic) membrane proteins showed that asparagine(N)-linked oligosaccharides are localized to single extracytosolic segments. In most membrane proteins this is because potential consensus sites for N-glycosylation (Asn-Xaa-Ser/Thr, X not equal to Pro) are not found in multiple extracytosolic segments. In functional proteins where consensus N-glycosylation sites are contained within more than one extracytosolic segment, only the first segment contains N-linked carbohydrate. An exception is the alpha-subunit of the Na+ channel, which consists of a duplicated structure containing two glycosylated segments. The average size of established N-glycosylated loops connecting two transmembrane segments is 62 residues, with the smallest glycosylated loop being 33 residues in size. N-glycosylated sites are more highly conserved than non-glycosylated (primarily cytosolic) sites and are more common toward the N-terminus of the membrane domain of multi-span membrane proteins. The optimal conditions for glycosylation of consensus sites within an extracytosolic domain of a multi-span membrane protein are (i) the acceptor site is well-spaced (greater than 10 residues) from the transmembrane domain, (ii) the loop is greater than 30 residues in size and (iii) the segment is the first in the protein to contain a suitable extracytosolic consensus site. The localization of N-linked oligosaccharide chains to a single protein segment suggests either glycosylation of multiple loops may compromise protein folding or function, or only a single polypeptide domain can be optimally glycosylated during biosynthesis in vivo.

Amino Acid Sequence↗
PubMed1984

Word recognition with segmented-alternated CVC words: a preliminary report on listeners with normal hearing.

Consonant-vowel-consonant (CVC) monosyllabic words were segmented at the approximate phoneme boundaries and were presented to subjects with normal hearing in the following sequence: (a) the carrier phrase to both ears, (b) the initial consonant segment to one ear, (c) the vowel segment to the other ear, and (d) the final consonant segment to the ear that received the initial consonant. A computer technique, which is described in detail, was used to develop the test materials. The digital editing did not alter appreciably the spectral or temporal characteristics of the words. A series of four experiments produced a list of 50 words on which 10% correct word recognition was achieved by listeners with normal hearing when the vowel segment or the consonant segments of the words were presented monaurally in isolation. When the speech materials were presented binaurally--that is, the vowel segment in one ear and consonant segments in the other ear--word-recognition performance improved to 90% correct.

Adult↗
PubMed2000

Segmental timing in amyotrophic lateral sclerosis.

This study describes segmental timing patterns for a passage read by speakers with ALS and a group of age- and gender-matched neurologically healthy speakers. Segment durations for ALS speakers' habitual rates (ALS condition) were compared to segment durations for healthy speakers' habitual and slow reading rates (Control Habitual and Control Slow conditions). Temporal differences for pairs of sound classes (i.e., long-short vowels, voiceless-voiced fricatives, voiceless-voiced stop gaps, high-low vowels) and prepausal lengthening of vowels also were studied. The results of the ALS-Control Habitual comparison suggested that the slowed articulatory rate of ALS influences segmental timing for most phonetic events. The finding that local segmental cues for disordered speakers were broadly consistent with their overall (slow) articulatory rate suggests that duration likely does not contribute in a significant way to intelligibility deficits in ALS. A qualitative analysis further indicated that the slowed rate of ALS is not uniformly distributed across phonetic events, but influences segment durations of particular sound categories in ways consistent with the disease process. The analysis comparing segment durations for the ALS and Control Slow conditions suggested that the overall pattern of segmental timing for speakers with ALS was broadly similar to the pattern for voluntarily slowed speech of healthy talkers. Finally, temporal differences for sound classes (i.e., voiceless-voiced fricatives, long-short vowels) and prepausal lengthening for speakers with ALS typically were similar to healthy speakers' habitual and slow speech. There were substantial variability within speaker groups and reversals of expected effects, however. The implication is that temporal differences for sound classes, such as short and long vowels, are not a particularly reliable perceptual cue for listeners.

Adult↗
PubMed2002

Removal of bronchoalveolar cells augments the late eosinophilic response to segmental allergen challenge.

BACKGROUND: In patients with quiescent asthma, macrophages are the most prevalent cells recovered by bronchoalveolar lavage (BAL). Through activation via their FcepsilonRII receptors or by acting as antigen-presenting cells, macrophages could, in theory, promote the late airway response to allergen. OBJECTIVE: In order to investigate the importance of macrophages and other airway luminal cells in inducing the late airway response, a novel washout experiment was designed. METHODS: Five patients with ragweed-allergic asthma underwent bronchoscopy and segmental bronchial challenge with either normal saline or short ragweed extract in two segments of one lung. In a third segment of the opposite lung, 12 successive BALs (25 mL each) were performed, followed by challenge with an identical dose of short ragweed (washed-challenged segment). After 24 h, all three challenged segments underwent BAL. RESULTS: Initially, in the washed-challenged segment, over 80% (mean 80.4%, range 68-88%) of the recoverable airway dwelling cells were removed. Unexpectedly, 24 h later these same washed-challenged segments contained more eosinophils in the BAL than the challenged segments from the opposite lung (P = 0.033). CONCLUSIONS: Removing the majority of airway luminal cells followed by allergen bronchoprovocation increased the number of eosinophils recovered 24 h after challenge. Our results suggest that in quiescent allergic asthma, the airway luminal cells are protective and attenuate the late eosinophilic response to allergen challenge.

Adult↗
PubMed2003

Imagent improves endocardial border delineation, inter-reader agreement, and the accuracy of segmental wall motion assessment.

BACKGROUND: This study was conducted to assess the ability of a new echocardiographic contrast agent, Imagent (perflexane lipid microspheres; Alliance Pharmaceutical Corp., San Diego, CA), to improve endocardial border delineation (EBD) and assessment of segmental wall motion (SWM). This was achieved by analysis of inter-reader agreement by echocardiography and comparison with an independent imaging technique, magnetic resonance imaging (MRI). METHODS: Two separate, independent, prospective, randomized, controlled, multicenter trials were conducted at 26 centers and included a total of 409 efficacy-evaluable patients. In Study A 206 patients were randomized to receive either Imagent or saline and in Study B, 203 patients received Imagent with a subset imaged by both echocardiography and MRI. All patients were required to have suboptimal baseline images using fundamental imaging. Images were optimized at baseline prior to contrast and the settings maintained post-contrast. Imagent, a suspension of perfluorohexane-filled spheres with flexible lipid shells, was administered as an IV bolus at 0.125 mg/kg body weight. Gated MRI studies were performed within 48 hours of dosing in a subset of 26 subjects. Six expert independent blinded readers reviewed unpaired noncontrast and contrast exams and scored EBD and SWM. Analysis of inter-reader agreement was performed by comparing the SWM score (1 to 5) recorded by each reader pair. In addition, unanimity between readers for SWM was evaluated. For comparison to MRI, the results from echo readers 4, 5, and 6 were each compared with a single independent MRI reader. RESULTS: The patients enrolled in these clinical trials displayed markedly suboptimal images with 49% and 71% (Study A and Study B) of the segments determined by the readers to be suboptimal prior to contrast administration. All readers recorded statistically significant (P < 0.0001) improvement in total EBD scores following the administration of Imagent. Comparison of noncontrast SWM scores for each pair of echo readers resulted in agreement in an average of 39%, of segments in Study A, and 31% of the segments in Study B. Use of Imagent improved agreement in SWM scores to 65% in Study A, and 48% of segments in Study B (P < 0.0001) for all reader pairs in both studies. Reader unanimity in SWM scores increased from 13% to 41% of the segments with the administration of Imagent. Blinded review of the noncontrast echo examinations resulted in agreement with MRI derived SWM scores in 15% of the segments. The administration of Imagent improved this agreement to 47%, of the segments (P < pr = 0.0005 for each blinded reader). CONCLUSIONS: Use of Imagent during echocardiographic imaging improves EBD, providing a significant improvement in inter-reader agreement in SWM evaluation with echo and greater than a threefold improvement in SWM scoring accuracy with MRI.

Adult↗
PubMed2002

Electrocardiographic ST segment elevation: a comparison of AMI and non-AMI ECG syndromes.

Chest pain (CP) patients presenting to the ED may manifest electrocardiographic ST segment elevation (STE). AMI (acute myocardial infarction) is a less frequent cause of such abnormality and one of many patterns responsible for ST segment elevation in ED CP patients. We performed a retrospective comparative review of the electrocardiographic features of various STE syndromes, focusing on differences between AMI and non-AMI syndromes. The electrocardiograms (ECGs) of consecutive ED adult CP patients (with 3 serial troponin I determinations) were interpreted by 3 attending emergency physicians. These ECGs with STE represented the study population used for analysis. Various electrocardiographic features such as STE, ST segment depression (STD), STE morphology, anatomic distribution of STE, and the number of leads with STE were recorded; derived values such as total STE, total ST segment deviation, and average STE per lead were calculated. Interobserver reliability concerning STE morphology was determined. AMI was diagnosed by abnormal serum troponin I values (>0.1 mg/dL) followed by a rise and fall of the serum marker; STE diagnoses of non-AMI causes were determined by medical record review. Five hundred ninety-nine CP patients were entered in the study with 212 (35%) individuals showing STE, 55 (26%) with electrocardiographic AMI and 157 (74%) with non-AMI electrocardiographic syndromes. Anatomic location within the AMI group included 32 inferior and inferior variants, 18 anterior and anterior variants, and 5 lateral; non-AMI anatomic locations included 56 inferior and inferior variants, 98 anterior and anterior variants, and 3 lateral; anterior STE occurred significantly more often in non-AMI syndromes. Total STE was 15.3 mm in AMI patients and 7.4 mm in non-AMI patients (P =.0004). The number of leads with STE was not significantly different between the two groups, 3.4 mm in AMI and 4.1 in non-AMI syndromes. ST segment elevation per lead was not significantly different in the 2 groups, 4.4 mm in AMI versus 1.8 mm in non-AMI syndromes. Total ST segment deviation (sum of STE and STD) was significantly greater in AMI syndromes, 17.8 mm in AMI compared with 10.5 mm in non-AMI syndromes (P =.00009). The presence of STD occurred at statistically similar rates in both groups. The morphology of the STE occurred in significantly different rates between AMI and non-AMI patterns, concave more often in non-AMI patterns (P <.00001) and nonconcave more often in AMI (P <.00001). Non-AMI causes of STE account for the majority of electrocardiographic syndromes encountered in ED chest pain patients. These findings alone are not adequate to determine the electrocardiographic cause of the ST segment elevation in chest pain patients. When determining AMI versus non-AMI with the ECG, these various findings should be used in the consideration of the overall clinical picture (history, examination, and electrocardiogram) in chest pain patients with ST segment elevation.

Angina Pectoris↗
PubMed1999

Comparison of the predictive value of ST segment elevation resolution at 90 and 180 min after start of streptokinase in acute myocardial infarction. A substudy of the hirudin for improvement of thrombolysis (HIT)-4 study.

AIMS: Previous studies revealed that >/=70% or <30% ST segment elevation resolution 180 min after the start of thrombolysis is a strong predictor of either favourable or poor outcome. The aim of this study was to compare the prognostic value of ST segment elevation resolution at 90 and 180 min after the start of streptokinase infusion. METHODS AND RESULTS: The Hirudin for Improvement of Thrombolysis (HIT)-4 study of 1208 patients compared streptokinase therapy in conjunction with either r-hirudin or heparin. Complete ST segment elevation resolution (>/=70%) at 90 and 180 min identified 25% and 50%, respectively, of all patients with a 30 day cardiac mortality of less than 2%. Forty-four percent of patients had no ST segment elevation resolution (<30%) at 90 min and the 30 day cardiac mortality was 7.3%. At 180 min, the no ST segment elevation resolution group decreased to 15% of all patients while the mortality risk increased to 13.6%. CONCLUSIONS: ST segment elevation resolution is a useful tool for early risk stratification and the strategy of rescue angioplasty. Complete ST segment elevation resolution within 180 min of the start of streptokinase therapy indicates excellent survival prospects in 50% of patients. A half of these low risk patients can be identified at 90 min. A high risk group appears to be best characterized by no ST segment elevation resolution at 180 min rather than at 90 min.

Double-Blind Method↗
PubMed2000

Lumbosacral transitional segments: classification, prevalence, and effect on disk height.

OBJECTIVE: To determine the rate of lumbosacral transitional segments among chiropractic practice settings and to determine if this anomaly would affect the height of the lumbosacral disk. STUDY DESIGN: Retrospective review of radiographs. SETTING: Los Angeles College of Chiropractic outpatient clinic and a private chiropractic office. SAMPLES: A total of 20 lumbar series with lumbosacral transitional segments from a private chiropractic office, 47 lumbar series with lumbosacral transitional segments, and 60 age- and sex-matched control series from a college clinic. RESULTS: A total of 2.3% of 882 lumbar series at the private chiropractic office and 6.5% of 786 lumbar series at the Whittier Health Center showed lumbosacral transitional segments of types II, III, or IV. The L5-S1 intervertebral disk height was significantly smaller in patients with lumbosacral transitional segments compared with those without (ie, 11% vs 19% of total lumbar disk height, respectively). When bilateral bony fusion of L5 to the sacrum was present, the L5-S1 disk height was significantly smaller than that without bony fusion (ie, 8% vs. 12% to 14% of total lumbar disk height, respectively). CONCLUSIONS: We conclude that the rate of occurrence of lumbosacral transitional segments is low in chiropractic practice. In the presence of lumbosacral transitional segments, especially when there was bony fusion, the lumbosacral intervertebral disk was significantly narrower than the upper lumbar disks, which should not be considered as disk degeneration or displacement. The type of lumbosacral transitional segment present also showed a significant effect on the height of the lumbosacral disk.

Adolescent↗
PubMedDate not supplied

Myocardial perfusion and angiographic correlations in patients with ST-segment elevation during dobutamine stress perfusion imaging.

BACKGROUND: There is scanty information on the angiographic and myocardial perfusion correlates of dobutamine-induced ST-segment elevation. METHODS AND RESULTS: We studied 39 patients who exhibited ST-segment elevation during dobutamine perfusion tomography and had recent coronary angiography performed (ie, within 3 months of the dobutamine study). Baseline characteristics, extent of coronary artery disease, relationship of Q waves to ST-segment elevation, ischemic burden, and angiographic findings were assessed. Twenty-nine patients (74%) had prior myocardial infarction, and 77% had abnormal Q waves at baseline. Ninety-three percent of patients had abnormal perfusion imaging. Eighty percent of patients had multivessel coronary artery disease. The left ventricular ejection fraction by contrast ventriculography was 35% +/- 7% (mean +/- SD), the perfusion defect size was 32% +/- 15%, and 73% of patients had some degree of myocardial ischemia. A predominance of ischemia (>50% reversibility) occurred in 38% of patients with Q waves and in 70% of those without Q waves. There was also good agreement between the site of ST-segment elevation and the site of ischemia by perfusion imaging (79%) and between the site of ST-segment elevation and the location of the vessel with significant coronary stenosis (95%). CONCLUSIONS: Patients with dobutamine-induced ST-segment elevation have a depressed left ventricular ejection fraction, a high frequency of multivessel disease, and markedly abnormal myocardial perfusion tomography. In patients with ST-segment elevation and abnormal Q waves, substantial scarring and superimposed ischemia coexist, whereas in patients without Q waves, ST-segment elevation usually denotes severe ischemia.

Adrenergic beta-Agonists↗
PubMed1984

Lengths of chromosomal segments conserved since divergence of man and mouse.

Linkage relationships of homologous loci in man and mouse were used to estimate the mean length of autosomal segments conserved during evolution. Comparison of the locations of greater than 83 homologous loci revealed 13 conserved segments. Map distances between the outermost markers of these 13 segments are known for the mouse and range from 1 to 24 centimorgans. Methods were developed for using this sample of conserved segments to estimate the mean length of all conserved autosomal segments in the genome. This mean length was estimated to be 8.1 +/- 1.6 centimorgans. Evidence is presented suggesting that chromosomal rearrangements that determine the lengths of these segments are randomly distributed within the genome. The estimated mean length of conserved segments was used to predict the probability that certain loci, such as peptidase-3 and renin, are linked in man given that homologous loci are chi centimorgans apart in the mouse. The mean length of conserved segments was also used to estimate the number of chromosomal rearrangements that have disrupted linkage since divergence of man and mouse. This estimate was shown to be 178 +/- 39 rearrangements.

Animals↗
PubMed1987

Segment-specific inverted repeats found adjacent to conserved terminal sequences in wound tumor virus genome and defective interfering RNAs.

Defective interfering (DI) RNAs are often associated with transmission-defective isolates of wound tumor virus (WTV), a plant virus member of the Reoviridae. We report here the cloning and characterization of WTV genome segment S5 [2613 base pairs (bp)] and three related DI RNAs (587-776 bp). Each DI RNA was generated by a simple internal deletion event that resulted in no sequence rearrangement at the deletion boundaries. Remarkably, although several DI RNAs have been in continuous passage for more than 20 years, their nucleotide sequences are identical to that of corresponding portions of segment S5 present in infrequently passaged, standard, transmission-competent virus. The positions of the deletion breakpoints indicate that the minimal sequence information required for replication and packaging of segment S5 resides within 319 bp from the 5' end of the (+)-strand and 205 bp from the 3' end of the (+)-strand. The terminal portions of segment S5 were found to contain a 9-bp inverted repeat immediately adjacent to the conserved terminal 5'-hexanucleotide and 3'-tetranucleotide sequences shared by all 12 WTV genome segments. The presence of a 6- to 9-nucleotide segment-specific inverted repeat immediately adjacent to the conserved terminal sequences was found to be a feature common to all WTV genome segments. These results reveal several basic principles that govern the replication and packaging of a segmented double-stranded RNA genome.

Amino Acid Sequence↗
PubMed1991

Two distinct alpha beta T-cell lineages can be distinguished by the differential usage of T-cell receptor V beta gene segments.

Avian T cells can be divided into three subpopulations based on their expression of distinct T-cell receptors (TCR1, TCR2, and TCR3), ontogeny, and tissue distribution. The TCR1 cells appear to be the equivalent of mammalian gamma delta cells, but the derivation of cells expressing TCR2 and TCR3 has been unclear. Here we report that chickens contain two families of TCR beta variable (V) gene segments, V beta 1 and V beta 2. Furthermore, TCR2 and TCR3 represent subsets of alpha beta cells that are defined by mutually exclusive usage of these two families of V beta gene segments. Sequence comparisons of V beta 1 and V beta 2 with mammalian TCR beta V segments reveal that V beta 1 gene segments encode the conserved amino acids used to define the mammalian V beta consensus subgroup I, while V beta 2 encodes the amino acids used to define the mammalian V beta subgroup II. Although the beta chains of TCR2 and TCR3 cells are encoded by the same diversity (D), joining (J), and constant (C) region segments, V beta 1 gene segments undergo rearrangement before V beta 2 gene segments during T-cell development. This may result from the fact that TCR2 cells undergo V-DJ joining by deletional rearrangement, whereas TCR3 cells undergo V-DJ joining by inversional rearrangement. These data suggest that the TCR alpha beta cells can be divided into two distinct and evolutionarily conserved lineages based on V beta gene segment usage. The clear-cut separation of these lineages in the chicken may help to define their immunologic role.

Aging↗
PubMed1993

Identification of a precursor genomic segment that provided a sequence unique to glycophorin B and E genes.

Human glycophorin A, B, and E (GPA, GPB, and GPE) genes belong to a gene family located at the long arm of chromosome 4. These three genes are homologous from the 5'-flanking sequence to the Alu sequence, which is 1 kb downstream from the exon encoding the transmembrane domain. Analysis of the Alu sequence and flanking direct repeat sequences suggested that the GPA gene most closely resembles the ancestral gene, whereas the GPB and GPE genes arose by homologous recombination within the Alu sequence, acquiring 3' sequences from an unrelated precursor genomic segment. Here we describe the identification of this putative precursor genomic segment. A human genomic library was screened by using the sequence of the 3' region of the GPB gene as a probe. The genomic clones isolated were found to contain an Alu sequence that appeared to be involved in the recombination. Downstream from the Alu sequence, the nucleotide sequence of the precursor genomic segment is almost identical to that of the GPB or GPE gene. In contrast, the upstream sequence of the genomic segment differs entirely from that of the GPA, GPB, and GPE genes. Conservation of the direct repeats flanking the Alu sequence of the genomic segment strongly suggests that the sequence of this genomic segment has been maintained during evolution. This identified genomic segment was found to reside downstream from the GPA gene by both gene mapping and in situ chromosomal localization. The precursor genomic segment was also identified in the orangutan genome, which is known to lack GPB and GPE genes. These results indicate that one of the duplicated ancestral glycophorin genes acquired a unique 3' sequence by unequal crossing-over through its Alu sequence and the further downstream Alu sequence present in the duplicated gene. Further duplication and divergence of this gene yielded the GPB and GPE genes.

Base Sequence↗