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Characterization of M-class genome segments of muscovy duck reovirus S14.

This report documents the first sequence analysis of the entire M1, M2, and M3 genome segments of the muscovy duck reovirus (DRV) S14. The complete sequence of each of the three M gene segments was determined. The M1 genome segment was 2283 nucleotides in length and was predicted to encode muA protein of 732 residues. The Escherichia coli expressed M1 transcripts generated a 108kDa protein, as expected for muA. A cleavage product of muA, muA1, could be detected by Western blotting with duck anti-reovirus and mouse anti-muA polyclonal serum. muA was distributed diffusely in the cytoplasma and nucleus of transfected Vero cells, which provides evidence that muA might be functional related to the mammalian reovirus (MRV) mu2. The M2 gene was 2155 nucleotides in length and was predicted to encode muB major outer capsid protein of 676 amino acids. The M3 genome segment was 1996 nucleotides in length and was predicted to encode a muNS protein of 635 amino acids. It was unexpectedly found that 5'-termini of the M1 and M2 genes ended with 5'-ACUUUU and 5'-UCUUUU, respectively, instead of 5'-GCUUUU, which is present on most mRNAs of other avian reoviruses (ARV). The UCAUC 3'-terminal sequences of the S14 M1, M2, and M3 genome segments are shared by DRV, ARV, and MRV. Alignment of the DRV muA-, muB-, and muNS-encoding genes with ARV revealed 72.9-73.9%, 67.1-69.6%, and 69.4-70.8% nucleotide identity, respectively. The amino acid sequence homology between DRV and ARV ranged from 85.3 to 86.2% (muA), 75.0 to 76.5% (muB), and 78.4 to 79.8% (muNS). Phylogenetic analyses of the M1, M2, M3, and S-class [Kuntz-Simon, G., Le Gall-Recule, G., de Boisseson, C., Jestin, V., 2002. Muscovy duck reovirus sigmaC protein is a typically encoded by the smallest genome segment. J. Gen. Virol. 83, 1189-1200; Zhang, Y., Liu, M., Hu, Q.L., Ouyang, S.D., Tong, G.Z., 2006a. Characterization of the sigmaC-encoding gene from muscovy duck reovirus. Virus Genes 36, 169-174; Zhang, Y., Liu, M., Ouyan, S.D., Hu, Q.L., Guo, D.C., Han, Z., 2006b. Detection and identification of avian, duck, and goose reoviruses by RT-PCR: goose and duck reoviruses aggregated the same specified genogroup in Orthoreovirus Genus II. Arch. Virol. 151, 1525-1538] genome segments suggests that DRV and ARV share a recent common ancestor and that the two lineages have subsequently undergone host dependent evolution.

Amino Acid Sequence↗

Generation of segment polarity in the paraxial mesoderm of the zebrafish through a T-box-dependent inductive event.

The first morphological sign of vertebrate postcranial body segmentation is the sequential production from posterior paraxial mesoderm of blocks of cells termed somites. Each of these embryonic structures is polarized along the anterior/posterior axis, a subdivision first distinguished by marker gene expression restricted to rostral or caudal territories of forming somites. To better understand the generation of segment polarity in vertebrates, we have studied the zebrafish mutant fused somites (fss), because its paraxial mesoderm lacks segment polarity. Previously examined markers of caudal half-segment identity are widely expressed, whereas markers of rostral identity are either missing or dramatically down-regulated, suggesting that the paraxial mesoderm of the fss mutant embryo is profoundly caudalized. These findings gave rise to a model for the formation of segment polarity in the zebrafish in which caudal is the default identity for paraxial mesoderm, upon which is patterned rostral identity in an fss-dependent manner. In contrast to this scheme, the caudal marker gene ephrinA1 was recently shown to be down-regulated in fss embryos. We now show that notch5, another caudal identity marker and a component of the Delta/Notch signaling system, is not expressed in the paraxial mesoderm of early segmentation stage fss embryos. We use cell transplantation to create genetic mosaics between fss and wild-type embryos in order to assay the requirement for fss function in notch5 expression. In contrast to the expression of rostral markers, which have a cell-autonomous requirement for fss, expression of notch5 is induced in fss cells at short range by nearby wild-type cells, indicating a cell-non-autonomous requirement for fss function in this process. These new data suggest that segment polarity is created in a three-step process in which cells that have assumed a rostral identity must subsequently communicate with their partially caudalized neighbors in order to induce the fully caudalized state.

Animals↗

The effect of lead selection on traditional and heart rate-adjusted ST segment analysis in the detection of coronary artery disease during exercise testing.

Several methods of heart rate-adjusted ST segment (ST/HR) analysis have been suggested to improve the diagnostic accuracy of exercise electrocardiography in the identification of coronary artery disease compared with traditional ST segment analysis. However, no comprehensive comparison of these methods on a lead-by-lead basis in all 12 electrocardiographic leads has been reported. This article compares the diagnostic performances of ST/HR hysteresis, ST/HR index, ST segment depression 3 minutes after recovery from exercise, and ST segment depression at peak exercise in a study population of 128 patients with angiographically proved coronary artery disease and 189 patients with a low likelihood of the disease. The methods were determined in each lead of the Mason-Likar modification of the standard 12-lead exercise electrocardiogram for each patient. The ST/HR hysteresis, ST/HR index, ST segment depression 3 minutes after recovery from exercise, and ST segment depression at peak exercise achieved more than 85% area under the receiver-operating characteristic curve in nine, none, three, and one of the 12 standard leads, respectively. The diagnostic performance of ST/HR hysteresis was significantly superior in each lead, with the exception of leads a VL and V1. Examination of individual leads in each study method revealed the high diagnostic performance of leads I and -aVR, indicating that the importance of these leads has been undervalued. In conclusion, the results indicate that when traditional ST segment analysis is used for the detection of coronary artery disease, more attention should be paid to the leads chosen for analysis, and lead-specific cut points should be applied. On the other hand, ST/HR hysteresis, which integrates the ST/HR depression of the exercise and recovery phases, seems to be relatively insensitive to the lead selection and significantly increases the diagnostic performance of exercise electrocardiography in the detection of coronary artery disease.

Coronary Disease↗

Use of coronary revascularization in patients with unstable and non-ST-segment elevation acute myocardial infarction.

Percutaneous coronary intervention can be safely performed in patients with acute coronary syndromes (ACS), including those with non-ST-segment elevation myocardial infarction (MI), and unstable angina. Although there remains debate about whether an aggressive strategy involving early coronary arteriography and revascularization should be routinely performed in patients who present with non-ST-segment elevation MI and unstable angina, recent clinical trials suggest that an aggressive approach should be taken in both intermediate- and high-risk patients with ACS. There have been 4 clinical trials that have compared the outcomes of patients presenting with non-ST-segment elevation MI or unstable angina who were assigned to invasive or conservative strategies. The Thrombolysis in Myocardial Infarction (TIMI) IIIB trial and the Veterans Affairs Non-Q-Wave Infarction Strategies in Hospital (VANQWISH) trial failed to demonstrate a reduction in death or MI in patients assigned to an invasive approach, but it did demonstrate an important reduction in the frequency of rehospitalization. However, these studies were performed before the availability of coronary stents or the use of glycoprotein IIb/IIIa inhibitors. In contrast, the Fragmin and Fast Revascularisation During Instability in Coronary Artery Disease (FRISC) II and the Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategy (TACTICS) trials demonstrated significant improvements in the rates of death or MI in patients with non-ST-segment elevation MI or unstable angina assigned to an invasive strategy. Event reductions were greatest in patients with non-ST-segment elevation MI or unstable angina at intermediate or high risk for an adverse outcome. Understanding that these subgroups comprise approximately 75% of patients presenting with non-ST-segment elevation MI or unstable angina, we believe that an invasive approach is indicated in most patients who develop non-ST-segment elevation MI or unstable angina. Regardless of the strategy used in ACS patients, lipid-lowering therapy is necessary to reduce recurrent ischemia events at the site of plaque instability and in atherosclerotic disease remote to the target lesion.

Angina, Unstable↗

The case for trial of labor in the patient with a prior low-segment vertical cesarean incision.

OBJECTIVE: Our purpose was to review recent obstetric literature detailing the subsequent delivery experience of patients with a prior low-segment vertical cesarean incision and to derive recommendations for practice on the basis of this information. STUDY DESIGN: Ten studies that included information about pregnancy outcome in patients with prior low-segment vertical cesarean operations were retrieved and reviewed from the American obstetric literature since 1981 and from a review of all abstracts presented annually since 1981 to the Society of Perinatal Obstetricians. RESULTS: Altogether, information about subsequent pregnancy outcome for 382 patients with prior low-segment vertical cesarean delivery was available for analysis. Among the 372 patients with complete patient population information, vaginal delivery was safely accomplished in 306 (82%). Four uterine ruptures (1.05%) have been reported, only one of which occurred after a single prior unextended low-segment vertical cesarean incision. Two ruptures occurred elsewhere on the lateral or posterior aspect of the uterus in subsequent pregnancies, and the fourth rupture occurred at the juncture of prior low vertical and transverse incisions. No perinatal mortality or permanent perinatal morbidity was encountered with these pregnancies. CONCLUSIONS: In the otherwise uncomplicated pregnancy the patient with one previous nonextended low-segment vertical cesarean incision should be considered to have a prior low-segment scar and as such be a candidate for trial of labor in her current singleton pregnancy. The same care, counseling, and caution should be exercised for this patient as for one with a prior low-segment transverse incision.

Birth Weight↗

Implantation of scleral expansion band segments for the treatment of presbyopia.

PURPOSE: To assess the effects of scleral expansion band (SEB) segments on accommodative amplitude (primary measure), along with near and distance vision, refraction, pupil size and function, keratometry, axial length, intraocular pressure, contrast sensitivity, stereopsis, and other parameters (secondary measures) in a cohort of 29 emmetropic, presbyopic patients. DESIGN: Multicenter, prospective, nonrandomized, unmasked clinical trial in which the nonoperated eye served as the control. METHODS: Four polymethylmethacrylate segments were surgically implanted in quadrantic scleral pockets created in the dominant eye of 29 emmetropic patients who were between the ages of 51 and 60 (mean age 54). Patients were examined preoperatively and up to 6 months postoperatively. The aforementioned tests were performed on the operated and control eye of each patient. Data were analyzed using two-sided rank tests. Medians, means, and standard deviations are provided for all measurements. RESULTS: Accommodative amplitude was measured monocularly using a near-point "push" technique from both a 70-cm and 30-cm starting point. An increase in accommodative amplitude of surgical eyes by +1.7 +/- 1.5 diopters and +1.5 +/- 1.2 diopters, at these two testing distances, respectively, was noted at 6 months postoperatively (P <.0001). A smaller increase was also seen in control eyes (+1.2 +/- 1.1 diopters and +1.3 +/- 1.2 diopters, respectively). There was notable intercenter variation in gains in accommodation, with three of seven centers showing significant improvement in near-point accommodative amplitudes relative to the others (P =.0003). There was a median improvement of uncorrected near acuity in surgical eyes by 0.3 logarithm of the minimal angle of resolution (logMAR) at 30 and 40 cm and by 4 lines at 20 cm, with the difference in near acuity improvement at 6 months between SEB eyes and control eyes statistically significant at 20 cm (P <.030). Changes in spherical equivalence, axial length, and central keratometry readings were not statistically significant. There were no reports of anterior segment ischemia or malignant glaucoma. Adverse effects were limited to a transient elevation of intraocular pressure in one patient and misalignment of individual SEB segments, due to inadequate scleral pocket formation, in three patients. Only one SEB segment in one eye was replaced. It appears that the thickness and uniformity of the scleral belt loop is critical to the proper positioning and efficacy of the SEB segments. CONCLUSION: While the safety profile of SEB segments for the treatment of presbyopia was high, a modest improvement in near vision was noted in approximately half the patients using subjective methods of testing. The mechanisms that underlie improvement in near vision in the nonoperated eye await explanation. This may be due to a centrally controlled consensual response, potentiated convergence generating increased intravitreal pressure and hydraulic lift of the vitreo-zonular-lens diaphragm, or artifact from current testing techniques. Future studies of the SEB procedure should address the issue of intercenter variation by further standardizing and automating specific aspects of the surgical technique, as well as incorporating objective testing methods into the study design.

Accommodation, Ocular↗

Development of spinal cord ischemia after clamping of noncritical segmental arteries in the pig.

BACKGROUND: Blood flow to the thoracolumbar spinal cord is thought to be critically dependent on the arteria radicularis magna. We investigated whether spinal cord blood supply becomes dependent on other, noncritical, segmental arteries if spinal cord perfusion pressure (SCPP) is decreased. The SCPP is equal to the mean arterial pressure (MAP) minus the cerebrospinal fluid (CSF) pressure (SCCP = MAP - CSF). METHODS: The thoracoabdominal aorta was exposed in 10 pigs. Functional integrity of spinal cord motor pathways was assessed with myogenic motor-evoked potentials after transcranial electrical stimulation (tc-MEPs). Using this technique, a group of segmental arteries not critical for spinal cord blood supply was identified. Before, during, and after clamping of the noncritical segmental arteries, spinal cord ischemia was produced by decreasing SCPP by means of increasing CSF pressure, and the SCPP threshold at which tc-MEPs showed evidence of spinal cord ischemia was determined. Ischemic SCPP thresholds, obtained during and after clamping of the noncritical segmental arteries, were compared with the ischemic threshold obtained before clamping (control value). RESULTS: Before noncritical segmental arteries were clamped, ischemic tc-MEP changes occurred when the SCPP was below 15 +/- 5 (SD) mm Hg. With a total of 9 +/- 3 (SD) segmental arteries clamped, the ischemic SCPP threshold was 48 +/- 14 mm Hg (p < 0.01). After the release of all clamps, ischemia occurred at a SCPP of 15 +/- 5 (SD) mm Hg. CONCLUSIONS: In this porcine experiment, clamping of originally noncritical segmental arteries significantly reduced the tolerance of the spinal cord to a decrease in SCPP.

Animals↗

The protocadherin papc is involved in the organization of the epithelium along the segmental border during mouse somitogenesis.

The anterior and posterior halves of individual somites adopt distinct fates during somitogenesis, which is crucial for establishing the metameric pattern of axial tissues such as the vertebral column and peripheral nerves. Genetic analyses have demonstrated that the specification of cells to an anterior or posterior fate is intimately related to the process of segmentation. Inactivation of the transcription factor Mesp2, or components of the Notch signaling pathway, led to defects in segmentation and a loss of anterior/posterior polarity. Target genes in mice that could mediate the morphological events associated with segmentation or polarity have not been identified. Studies in Xenopus and zebrafish have demonstrated that the protocadherin, papc, is expressed in an anterior-specific manner in the presumptive somites of the presomitic mesoderm and is required for normal somitogenesis. Here, we examine the role of papc in directing segmentation in the mouse. We demonstrate that papc is expressed in a dynamic pattern within the first two presumptive somites (0 and -1) at the anterior end of the presomitic mesoderm. The domain of papc transcription in somite 0 starts broad and becomes progressively restricted to the anterior edge. Transcription in somite -1 over the same time remains broad. Analysis of targeted null mutations revealed that transcription of papc is dependent on Mesp2. The dynamic nature of papc transcription in somite 0 requires the expression of lunatic fringe, which modifies the activation of the Notch signaling pathway and is required for proper segmentation of somites. Treatment of embryonic mouse tails in a hanging drop culture with a putative dominant-negative mutation of papc disrupted the epithelial organization of cells at the segmental borders between somites. Together, these data indicate that papc is an important regulator of somite epithelialization associated with segmentation.

Animals↗

An epithelial-derived factor inhibits contraction in canine perfused bronchial segments.

We have previously reported, using a novel preparation of canine airway segments, that the sensitivity of acetylcholine was greater when applied to the adventitial (outside) surface than the epithelial (inside) surface. The present study investigated if this "barrier-effect" was partly the result of pharmacological modulation by the epithelium. As previously demonstrated, canine airway segments were less sensitive to inside than outside application of acetylcholine (pD(2) 3.0+/-0.4 and 4.5+/-0.4, respectively, P<0.001, n=5). The addition of donor bronchi significantly decreased the sensitivity of the airway segment to outside application of acetylcholine (pD(2) 4.3+/-0.2 and 3.6+/-0.2, respectively, P<0.002, n=4). Indomethacin (2.5 microM) treatment of both the donor bronchi and the airway segment and removal of donor epithelium abolished the rightward shift in the acetylcholine-response curves. In addition, inhibition of cyclooxygenase within the airway segments themselves, but not the donor bronchi, also inhibited the rightward shift in the curves. These results indicate that the donor epithelium is capable of pharmacologically modulating responses of the airway segment to outside applied acetylcholine by producing an epithelial-derived factor, which in turn causes the release of a downstream cyclooxygenase product from within the airway segment.

Acetylcholine↗

A comparison of ST segment deviation and calculated solid angle during acute regional ischemia in the isolated canine heart at precordial, epicardial and intramyocardial lead surfaces.

Although solid angle analysis has been considered to be reasonable for explaining the distribution of ST segment deviation following ischemia, it has not been tested fully, especially for ST segment changes in various sites at different lead surfaces. Thus, we investigated the applicability of solid angle theory to the mechanism of ischemic ST segment deviation at intramyocardial, epicardial and precordial leads. We used seven isolated, coronary perfused, isovolumic contracting canine hearts in a homogeneous cylindrical volume conductor. ST segment potentials from 246 electrodes were continuously measured during left circumflex coronary artery occlusion for five minutes. The ischemic boundary was obtained from a postmortem angiography, and the solid angle subtended by the ischemic boundary was calculated at every electrode site. Despite the difference between epicardial and precordial ST segment potential distributions, there was a high correlation between measured ST segment potential and calculated solid angle at epicardial (r = 0.86 +/- 0.05, 0.77-0.93), precordial (r = 0.93 +/- 0.05, 0.84-0.99), and intramyocardial leads (r = 0.95 +/- 0.03, 0.91-0.99). We conclude that solid angle analysis can be used to approximate the distribution of ischemic ST segment deviation at different lead surfaces in acute ischemia.

Animals↗

Simultaneous ST-segment elevation in lead V1 and depression in lead V2. A discordant ECG pattern indicating right ventricular infarction.

The major electrocardiographic change in right ventricular infarction (RVI) is ST-segment elevation in leads V4R-V6R. The authors describe a discordant electrocardiographic pattern of ST-segment elevation in lead V1 and ST-segment depression in lead V2 in five patients presenting with acute transmural (Q wave) inferior infarction and RVI. There were 51 patients with transmural inferior infarction from a thrombolytic trial. In 25 patients, the ST-segment in the right-sided precordial leads was elevated by > or = 1 mm indicating the presence of RVI. In 5 of these 25 patients, simultaneous ST-segment elevation of 1.0-8.0 mm (mean, 2.8 +/- 2.9 mm) in lead V1 and ST-segment depression of 2.5 to 4.0 mm (mean, 3.3 +/- 0.6 mm) in lead V2 were also present. The discordant pattern of the ST-segments in leads V1 and V2 is an important and specific sign for RVI.

Adult↗

Bedside diagnosis of myocardial ischemia with ST-segment monitoring technology: measurement issues for real-time clinical decision making and trial designs.

Monitoring of the ST segment is a valuable tool for guiding clinical decision making and evaluating anti-ischemia interventions in clinical trials; however, measurement issues hamper its diagnostic accuracy. This study reports the frequency and type of false positives and other measurement issues we have encountered during 12-lead ST-segment monitoring of patients in a cardiac care unit. Of 292 patients, 117 (40%) had one or more false positive events during an average of 41 hours of ST-segment monitoring, for a total of 506 false positive events. The 506 false positive events included 167 (36%) due to body positional change; 132 (26%) due to sudden increase in QRS complex/ST-segment voltage; 96 (19%) due to transient arrhythmia or pacing; 80 (16%) due to heart rate change in steeply sloped ST-segment contours; 26 (5%) due to a noisy signal; and 5 (1%) due to lead misplacement. It is concluded that many conditions in addition to myocardial ischemia can cause transient ST-segment deviation in patients with unstable coronary syndromes. Accurate ST-segment monitoring requires expertise in electrocardiogram interpretation, an understanding of the patient's clinical situation, and knowledge of the functions and limitations of the ST-segment monitoring system.

Aged↗

Successful in vivo and ex vivo transfection of pulmonary artery segments in lung isografts.

OBJECTIVE: Gene transfer to lung grafts may be useful in ameliorating ischemia-reperfusion injury and rejection. Efficient gene transfection to the whole organ may prove problematic. Proximal pulmonary artery endothelial transfection might provide beneficial downstream effects on the whole graft. The aim of this study was to determine the feasibility of transfecting proximal pulmonary artery segments in lung isografts. METHODS: Male Fischer rats were divided into six groups. In vivo transfection: In group I (n = 7), a proximal segment of the left pulmonary artery was isolated and injected with saline solution by means of a catheter inserted through the right ventricle. After an exposure period of 20 minutes, clamps were removed and blood flow was restored. In group II (n = 7), the isolated arterial segments were injected with adenovirus carrying the Escherichia coli LacZ gene encoding for beta-galactosidase. Ex vivo transfection: In group III (n = 5), arterial segments were injected ex vivo with saline solution and in group IV (n = 5) with the adenovirus construct. In group V (n = 6), arteries were injected with saline solution and in group VI (n = 11) with liposome chloramphenicol acetyl transferase cDNA. In groups I to IV, animals were killed on postoperative day 3 and transgene expression was assessed by Bluo-Gal staining. In groups V and VI, animals were killed on postoperative day 2 and transgene expression was assessed by chloramphenicol acetyl transferase activity assay. RESULTS: Transgene expression was detected grossly and microscopically in endothelial and smooth muscle cells of pulmonary artery segments from all surviving animals of groups II and IV. In group VI, chloramphenicol acetyl transferase activity was significant in all assessed arterial segments. CONCLUSION: Significant transgene expression is observed in proximal pulmonary artery segments after both in vivo and ex vivo exposure.

Animals↗

Beta-adrenergic receptors regulating vascular smooth muscle tone are only localized to the intraocular segment of the long posterior ciliary artery in bovine eye.

Beta-adrenergic drugs are important drugs in glaucoma treatment. Their exact mechanism of action is not yet fully understood but a decreased perfusion pressure in the ciliary body due to blockade of vasodilatory beta-adrenoceptors is thought to participate in the reduction of intraocular pressure. This study investigates the vasodilator action of beta adrenergic-agents in intra- and extraocular arteries from bovine and human eyes. Ring segments of retinal, choroidal, intraocular segment of long posterior ciliary artery, and segments of extraocular posterior ciliary arteries from bovine eyes and short posterior ciliary arteries from freshly enucleated human eyes were mounted on an isometric myograph and their reactivity to beta-adrenergic drugs were studied. Of all vessel types examined only the intraocular segment of long posterior ciliary artery precontracted with prostaglandin F2 alpha responded to 1-isoprenaline (1 nM-1 microM) with a graded concentration-dependent relaxation (32 +/- 7%, n = 10) and a pD2 of 7.5 +/- 0.2 concentrations of 1-isoprenaline greater than 1 microM induced contractions which were antagonized by a combined blockade of alpha1- and alpha2-adrenoceptors. Salbutamol (selective beta2-agonist) induced relaxations of similar magnitude as that of 1-isoprenaline but the sensitivity of the intraocular segment of long posterior ciliary arteries to salbutamol was 312 times less than that to 1-isoprenaline, pD2 7.2 +/- 0.2 and 4.4 +/- 0.1 (n = 6), respectively, whereas dobutamine (selective beta 1-agonist) had no effect between 1 nM and 10 microM. Betaxolol (selective beta 1-antagonist) and 1CI 115811 (selective beta 2-antagonist) competitively antagonized isoprenaline-induced relaxations giving pKB-values of 5.9 +/- 0.1 (n = 11) and 8.5 +/- 0.1 (n = 6), respectively. The slope of the Schild-plots were equal to unity. Human posterior ciliary arteries with spontaneous tone or tone induced by 10 microM PGF2 alpha did not react to isoprenaline (1 nM-10 microM). The bovine intraocular segment of long posterior ciliary arteries contracted to 1-noradrenaline without alpha-adrenoceptor blockade and addition of propranolol or cocaine did not change the concentration-response curve. 1-Phenylephrine and B-HT933 induced both potent and strong contractions indicating the presence of both alpha 1- and alpha 2-adrenoceptors in these arteries. Although beta-adrenoceptors have been identified in various parts of the ocular circulation by radio-ligand binding techniques our data show that beta-adrenoceptors linked to regulation of vascular tone are only found in intraocular branches of the intraocular segment of long posterior ciliary artery in bovine eyes.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic alpha-Antagonists↗

Segmentation of the paraxial mesoderm and vertebrate somitogenesis.

Somites are the most obviously segmented features of the vertebrate embryo. Although the way segmentation is achieved in the fly is now well described, little was known about the molecular mechanisms underlying vertebrate somitogenesis. Through the recent identification of genes important for vertebrate somitogenesis and the analysis of their function, several theoretical models accounting for somitogenesis such as the clock and wavefront model, which have been proposed over the past 20 years, are now starting to receive experimental support. A molecular clock linked to somitogenesis has been identified which might act as a periodicity generator in the presomitic cells. This temporal periodicity is then translated into a tightly controlled spatial periodicity which is revealed by the expression of several genes. Analysis of mouse mutants in the Notch-Delta pathway suggest that this signaling mechanism might play an important role at this level. The final step of the cascade is to translate these genetically specified segments into morphological units: the somites. Importantly, these studies have helped in dissociating the segmentation and the somitogenesis processes in vertebrates. In addition, although segmentation was classically thought to have arisen independently in protostomes and deuterostomes, recent evidence suggests that part of the segmentation machinery might actually have been conserved. The conservation of segmentation mechanisms reported in the fly such as the pair-rule pattern, however, remain a subject of controversy.

Animals↗

The blood supply of the hypoglossal nerve: the microsurgical anatomy of its cisternal segment.

BACKGROUND: While the characteristics of the vasculature of the second (intracanalicular) segment of the hypoglossal nerve are well known, the vascularization of the first (cisternal) segment of this nerve has not been examined so far. Many pathologic processes and malformations can be located in the premedullary cistern, which may affect the vasculature of the cisternal segment. Consequently, we decided to examine the blood supply of the cisternal segment. METHODS: The anatomic features of the cisternal segment and its vasculature were examined in 15 hypoglossal nerves after injection of india ink and gelatin into the vertebrobasilar arterial system. RESULTS: The cisternal segment was noted to consist of 3-15 long roots, which usually formed two trunks of the hypoglossal nerve. The roots of each nerve received blood from the anterolateral and the lateral medullary arteries, which ranged from 3 to 5 in number and between 100 microns and 500 microns in caliber. These arteries may arise from the perforating branches or the pontomedullary branch of the basilar artery; the vertebral artery or its perforators; the anterior spinal artery or its vascular roots; the posterior spinal artery; and the posterior inferior cerebellar artery. The main hypoglossal arteries, which ranged in diameter from 20 microns to 80 microns, always coursed along the dorsal surface of the roots of the hypoglossal nerve. CONCLUSIONS: The cisternal segment of the hypoglossal nerve was always vascularized by several vessels, which mainly originated from the vertebral artery and its branches. This observation was discussed from the neurosurgical point of view.

Cadaver↗

Variable region gene segment utilization in rhesus monkey hybridomas producing human red blood cell-specific antibodies: predominance of the VH4 family but not VH4-21 (V4-34).

Structural analyses of human immunoglobulin gene segments from monoclonal cell lines provide valuable information regarding the antibody repertoire. This information, in conjunction with a nearly complete knowledge of the human immunoglobulin germline repertoire, now allows further investigation into the underlying molecular basis responsible for some of the observed biases found in the expressed repertoire. One human heavy chain variable region gene segment, V4-34 (VH4-21), is one of the most prevalent gene segments in the expressed repertoire. The overwhelming presence of the V4-34 gene segment suggests that it may play an important role in immune responses. However, there is currently little information regarding its presence and potential importance in nonhuman primates. In order to determine if this gene segment is used by lower primates in a similar manner we determined the molecular structure of the variable region gene segments that are expressed by macaque monoclonal heterohybridomas that are specific for human red blood cell antigens. Eleven of the 12 hybridomas are derived from Rhesus monkeys (Macaca mulatta) and one is from a cynomologous monkey (Macaca fascicularis), all of which have been immunized with human red blood cells. The predominance of a VH4-like family and the specific absence of a VH4-21 equivalent led us to further characterize the macaque VH4 gene family at the germline level. Therefore, germline gene segments from the macaque equivalent to the human VH4 gene family are also described.

Animals↗

Visual segmentation of oriented textures by infants.

The infant's visual system contains orientation-sensitive mechanisms from the first weeks of life. Differences in texture orientation can serve as a basis for rapid preattentive localization and segmentation in adults. We tested whether infants could use their orientation-sensitive mechanisms in the same way, by forced-choice preferential looking, using displays of line segments oriented at 45 degrees in a rectangular patch and 135 degrees in the surrounding region. Performance was compared with that for displays of similar elements with uniform orientation but with the patch defined by luminance contrast. Infants of 14-18 weeks old showed consistent preference for both orientation- and contrast-defined patches, indicating the ability to segment the field by orientation. Infants of 8-12 weeks performed comparably to the older infants on contrast-based segmentation but did not show a statistically significant preference with orientation-based segmentation. In a second experiment, preference was also tested for a region of mixed orientation versus a region of uniform orientation. The 14-18-week-olds did not show this preference, suggesting that their preference for the discrepant texture patch genuinely reflected texture segmentation and not simply the presence of two different orientations on one side of the display. The results are discussed in terms of the possible maturation of intracortical connections subserving texture grouping and segmentation.

Aging↗