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Homeotic complex and teashirt genes co-operate to establish trunk segmental identities in Drosophila.

Homeotic genes determine the identities of metameres in Drosophila. We have examined functional aspects of the homeotic gene teashirt by ectopically expressing its product under the control of a heat-shock promoter during embryogenesis. Our results confirm that the gene is critical for segmental identity of the larva. Under mild heat-shock conditions, the Teashirt protein induces an almost complete transformation of the labial to prothoracic segmental identity, when expressed before 8 hours of development. Positive autoregulation of the endogenous teashirt gene and the presence of Sex combs reduced protein in the labium explain this homeosis. Patterns in the maxillary and a more anterior head segment are partly replaced with trunk ones. Additional Teashirt protein has no effect on the identity of the trunk segments where the gene is normally expressed; teashirt function is overridden by some homeotic complex acting in the posterior trunk. Strong heat-shock regimes provoke novel defects: ectopic sense organs differentiate in posterior abdominal segments and trunk pattern elements differentiate in the ninth abdominal segment. Teashirt acts in a partially redundant way with certain homeotic complex proteins but co-operates with them for the establishment of specific segment types. We suggest that Teashirt and HOM-C proteins regulate common sets of downstream target genes.

Animals↗

Control of Drosophila head segment identity by the bZIP homeotic gene cnc.

Mutational analysis of cap'n'collar (cnc), a bZIP transcription factor closely related to the mammalian erythroid factor NF-E2 (p45), indicates that it acts as a segment-specific selector gene controlling the identity of two cephalic segments. In the mandibular segment, cnc has a classical homeotic effect: mandibular structures are missing in cnc mutant larvae and replaced with duplicate maxillary structures. We propose that cnc functions in combination with the homeotic gene Deformed to specify mandibular development. Labral structures are also missing in cnc mutant larvae, where a distinct labral primordia is not properly maintained in the developing foregut, as observed by the failure to maintain and elaborate patterns of labral-specific segment polarity gene expression. Instead, the labral primordium fuses with the esophageal primordium to contribute to formation of the esophagus. The role of cnc in labral development is reciprocal to the role of homeotic gene forkhead, which has an identical function in the maintenance of the esophageal primordium. This role of homeotic selector genes for the segment-specific maintenance of segment polarity gene expression is a unique feature of segmentation in the preoral head region of Drosophila.

Animals↗

Notch signalling mediates segmentation of the Drosophila leg.

The legs of Drosophila are divided into segments along the proximodistal axis by flexible structures called joints. The separation between segments is already visible in the imaginal disc as folds of the epithelium, and cells at segment boundaries have different morphology during pupal development. We find that Notch is locally activated in distal cells of each segment, as demonstrated by the restricted expression of the Enhancer of split mbeta gene, and is required for the formation of normal joints. The genes fringe, Delta, Serrate and Suppressor of Hairless, also participate in Notch function during leg development, and their expression is localised within the leg segments with respect to segment boundaries. The failure to form joints when Notch signalling is compromised leads to shortened legs, suggesting that the correct specification of segment boundaries is critical for normal leg growth. The requirement for Notch during leg development resembles that seen during somite formation in vertebrates and at the dorsal ventral boundary of the wing, suggesting that the creation of boundaries of gene expression through Notch activation plays a conserved role in co-ordinating growth and patterning.

Animals↗

Hox genes differentially regulate Serrate to generate segment-specific structures.

Diversification of Drosophila segmental morphologies requires the functions of Hox transcription factors. However, there is little information describing pathways through which Hox activities effect the discrete cellular changes that diversify segmental architecture. We have identified the Drosophila signaling protein Serrate as the product of a Hox downstream gene that acts in many segments as a component of such pathways. In the embryonic epidermis, Serrate is required for morphogenesis of normal abdominal denticle belts and maxillary mouth hooks, both Hox-dependent structures. The Hox genes Ultrabithorax and abdominal-A are required to activate an early stripe of Serrate transcription in abdominal segments. In the abdominal epidermis, Serrate promotes denticle diversity by precisely localizing a single cell stripe of rhomboid expression, which generates a source of EGF signal that is not produced in thoracic epidermis. In the head, Deformed is required to activate Serrate transcription in the maxillary segment, where Serrate is required for normal mouth hook morphogenesis. However, Serrate does not require rhomboid function in the maxillary segment, suggesting that the Hox-Serrate pathway to segment-specific morphogenesis can be linked to more than one downstream function.

Animals↗

Segmental heterogeneity of epithelial ion transport induced by stimulants in rat distal colon.

Mammalian colon plays an important role in electrolyte and water balance, and exhibits significant segmental heterogeneity. The different responses to stimulants even exist in different segments of rat distal colon. The present study focus on the segmental heterogeneity of epithelial responses to different stimulants and investigates the possible mechanism by using short circuit current recording technique. Baseline I(SC) in the segment 4 of distal colon (DC(4), 20.8+/-2.8 microA.cm(-2)) was significantly lower than that in the segment 1 of distal colon (DC(1), 40.5+/-1.9 microA.cm(-2)). Basolateral application of indomethacin induced a larger reduction of the baseline I(SC) in DC(4) (-28.2+/-3.9 microA.cm(-2)) than that in DC(1) (-10.1+/-3.9 microA.cm(-2)). Moreover DC(4) are more sensitive to foskolin (a cAMP activator, apical side), Ach (basolateral side) and 5-HT (basolateral side) than DC(1), which was not affected by pretreatment with amiloride, a blocker of epithelial Na(+) channel. Basolateral pretreatment with atropine (muscarinic cholinergic receptor antagonist) for 10 min, Ach-induced DeltaI(SC) increases in both DC(1) and DC(4 )were totally blocked. Otherwise, 5-HT(4) receptor antagonist GR113808 (basolateral side) and SB-204070 (basolateral side) completely inhibited 5-HT-induced I(SC) increases in both DC(1) and DC(4). Taken together, the results suggested that the segmental heterogeneity of epithelial responses to different stimulants exists in rat distal colon. And it is more likely related to the dissimilar distribution of membrane proteins involved in the ion transports within different segments of rat distal colon.

Acetylcholine↗

The prognostic significance of exercise-induced silent ST-segment depression in patients after myocardial infarction.

To evaluate the prognostic value of exercise-induced silent ST-segment depression, 157 patients who had suffered myocardial infarction underwent symptom-limited exercise testing and coronary angiography. Patients were divided into 3 groups according to the presence or absence of ischemic ST-segment depression and angina during exercise testing. Group A patients had ST-segment depression without angina. Group B patients had both ST-segment depression and angina. Group C patients had neither ST-segment depression nor angina. All patients were followed without coronary artery bypass graft or percutaneous transluminal coronary angioplasty for an average of 36 months and the frequency of coronary events (cardiac death, recurrent myocardial infarction and unstable angina pectoris) was compared. Group A patients had less severe coronary artery disease, greater coronary reserve during exercise and exercised longer than group B. However, the prognosis of group A was similar to group B, and was worse than group C. Using the Cox proportional hazards model, ischemic ST-segment depression was the most useful index for predicting future coronary events among the baseline values, coronary angiographic and exercise testing variables. However, angina during exercise testing was not an independent predictor. Thus, post-infarction patients showing exercise-induced ST-segment depression should be treated carefully regardless of the presence or absence of angina.

Adult↗

Image segmentation in treatment planning for prostate cancer using the region growing technique.

The purpose of this study was to evaluate the performance of a region growing technique for segmenting prostate, bladder and rectum in CT images of prostate cancer patients. Prostate, bladder and rectum were segmented in all CT images of 10 patients using the region growing technique and manual tracing. Volumes of the above organs computed with the region growing technique were compared with those from manually traced images on a slice-by-slice basis. Measurement reproducibility of both segmentation techniques was evaluated using the data obtained from four independent observers. The region growing technique was 1.5 times faster than manual tracing. There was no statistical difference between the slice volumes of prostate, bladder and rectum obtained by the two segmentation techniques (p > 0.05, paired Student's t-test). Correlation between slice volumes of all organs of interest provided both by region growing and by manual tracing was very good (prostate r2 = 0.84; bladder r2 = 0.93; rectum r2 = 0.85). An overall reasonable agreement was found between the two segmentation techniques. The intraobserver and interobserver variations for prostate, bladder and rectum volume segmentation were found to be lower with the region growing technique than with manual tracing. The suggested semi-automatic technique allows the possibility of generating accurate and reproducible segmentation of prostate, bladder and rectum from CT data with great saving in labour.

Humans↗

Air pollution and ST-segment depression in elderly subjects.

Increased levels of daily ambient particle pollution have been associated with increased risk of cardiovascular morbidity. Black carbon (BC) is a measure of the traffic-related component of particles. We investigated associations between ambient pollution and ST-segment levels in a repeated-measures study including 269 observations on 24 active Boston residents 61-88 years of age, each observed up to 12 times from June through September 1999. The protocol involved continuous Holter electrocardiogram monitoring including 5 min of rest, 5 min of standing, 5 min of exercise outdoors, 5 min of recovery, and 20 cycles of paced breathing. Pollution-associated ST-depression was estimated for a 10th- to 90th-percentile change in BC. We calculated the average ST-segment level, referenced to the P-R isoelectric values, for each portion of the protocol. The mean BC level in the previous 12 hr, and the BC level 5 hr before testing, predicted ST-segment depression in most portions of the protocol, but the effect was strongest in the postexercise periods. During postexercise rest, an elevated BC level was associated with -0.1 mm ST-segment depression (p = 0.02 for 12-hr mean BC; p = 0.001 for 5-hr BC) in continuous models. Elevated BC also predicted increased risk of ST-segment depression > or = 0.5 mm among those with at least one episode of that level of ST-segment depression. Carbon monoxide was not a confounder of this association. ST-segment depression, possibly representing myocardial ischemia or inflammation, is associated with increased exposure to particles whose predominant source is traffic.

Aged↗

Efficient testing of segmented aspherical mirrors by use of reference plate and computer-generated holograms. I. Theory and system optimization.

Telescopes with large aspherical primary mirrors collect more light and are therefore sought after by astronomers. Instead of large mirrors as a single piece, they can be made by use of numerous smaller segments. Because the segments must fit together to create the effect of a single mirror, segmented optics present unique challenges to fabrication and testing that are absent for monolithic optics. We have developed a new method for measuring large quantities of segments accurately, quickly, and economically using an interferometric test plate and computer-generated hologram (CGH). In this test, the aspheric mirror segments are interferometrically measured by use of a test plate with a best-fit spherical surface. The aspherical departure is accommodated with a small CGH that is imaged onto the test plates. The radius of curvature is tightly controlled by maintaining the gap between the test plate and the segment. We present a summary of the test and give the basic design tradeoffs for using a single system to measure all of the segments of a large aspheric mirror.

Journal Article↗

Analytical study of diffraction effects in extremely large segmented telescopes.

We present an analysis of the diffraction effects from a segmented aperture with a very large number of segments-prototype of the next generation of extremely large telescopes. This analysis is based on the point-spread-function analytical calculation for Keck-type hexagonal segmentation geometry. We concentrate on the effects that lead to the appearance of speckles and/or a regular pattern of diffraction peaks. These effects are related to random piston and tip-tilt errors on each segment, gaps between segments, and segment edge distortion. We deliver formulas and the typical numerical values for the Strehl ratio, the relative intensity of higher-order diffraction peaks, and the averaged intensity of speckles associated with each particular case of segmentation error.

Journal Article↗

Topology and robustness in the Drosophila segment polarity network.

A complex hierarchy of genetic interactions converts a single-celled Drosophila melanogaster egg into a multicellular embryo with 14 segments. Previously, von Dassow et al. reported that a mathematical model of the genetic interactions that defined the polarity of segments (the segment polarity network) was robust (von Dassow et al. 2000). As quantitative information about the system was unavailable, parameters were sampled randomly. A surprisingly large fraction of these parameter sets allowed the model to maintain and elaborate on the segment polarity pattern. This robustness is due to the positive feedback of gene products on their own expression, which induces individual cells in a model segment to adopt different stable expression states (bistability) corresponding to different cell types in the segment polarity pattern. A positive feedback loop will only yield multiple stable states when the parameters that describe it satisfy a particular inequality. By testing which random parameter sets satisfy these inequalities, I show that bistability is necessary to form the segment polarity pattern and serves as a strong predictor of which parameter sets will succeed in forming the pattern. Although the original model was robust to parameter variation, it could not reproduce the observed effects of cell division on the pattern of gene expression. I present a modified version that incorporates recent experimental evidence and does successfully mimic the consequences of cell division. The behavior of this modified model can also be understood in terms of bistability in positive feedback of gene expression. I discuss how this topological property of networks provides robust pattern formation and how large changes in parameters can change the specific pattern produced by a network.

Animals↗

Painless ST-segment depression in patients with angina pectoris. Correlation with daily activities and cigarette smoking.

Ambulatory electrocardiographic monitoring was employed in 33 patients with angina pectoris and abnormal stress tests to determine the frequency with which myocardial ischemia manifested by painless ST-segment depression occurred during normal activity. ST-segment depression occurred in 24 patients during the monitoring period; and in 21, it occurred either solely in the absence of pain or both with and without pain. Of 109 recorded episodes of ST-segment depression, 61 percent were painless. The frequency of painless ST-segment depression was independent of activity other than automobile driving, during which all episodes were painless. In patients who smoked cigarettes, ST-segment depression was more common while smoking, but the incidence of painless ST-segment depression was not altered. The study indicates that ST-segment depression occurs more commonly in the absence than in the presence of chest pain and that ambulatory electrocardiographic monitoring is a useful method of determining the frequency of myocardial ischemia during normal daily activity.

Adult↗

Geometry of varicose veins segments.

The geometry of varicose vein segments, chosen from macroscopically normal as well as unmistakable dilated (bulbous) sites of the vessels, were studied in specimens obtained from stripping operations. Geometrical aspects (valves, dilatations) were studied on the vein slit open in axial direction and geometrical parameters (mean diameter, wall thickness) were measured on 3 sets of strips cut in circumferential direction with special reference to their location to the valves. In normal segments the vein is enlarged immediately proximal to the valves. In contrast to this, the bulbous and assymetric protrusions found in the diseased segments lie just below the valves, that is upstream. Values of diameters, wall thickness and wall thickness to diameter ratios are plotted as mean +/- SD in bar graphs. Results indicate that 1. the diameter has a maximum value at the valvular site both in the normal and the diseased segments; the normal diameters are smaller than the corresponding diseased ones. 2. The wall thickness increases from the distal to the proximal site in the normal segments, whereas it displays a minimum value at the valvular site of the bulbous segments. 3. The wall thickness to diameter ratios of both the normal and the pathological segments have a minimum at valvular site, but the normal values are larger than the corresponding pathological values, a behavior which is more apparent in the bulbous enlargements and even evident in the hypertrophied side of the wall opposite to the protrusions.

Humans↗

[Changes in intestinal motility after massive small bowel resection with a reversed jejunal segment].

To evaluate the functioning and effectiveness of a 20-cm reversed jejunal segment after 75-80% massive small bowel resection (MSBR), and whether migrating polarity changes or not, we continuously measured the postoperative bowel motility (using bipolar electrodes and/or contractile strain gage force transducers) in interdigestive and postprandial conscious dogs in short- (2-5 weeks) and long-term (6-10 months) after surgery. The fasting migrating myoelectric (or motor) complex (MMC) arising from the duodenum was often interrupted at the jejunum above the proximal anastomosis and did not migrate smoothly to the reversed segment or terminal ileum. In addition, brief small discordant contractions were frequent in the jejunum above the proximal anastomosis and the proximal part of the reversed segment. The duodenal MMCs predominantly propagated to the ileum through the inherent anatomic continuity of the bowel. These findings of the MMC propagation pattern are very similar in short- and in long-term after surgery. The duration of the postprandial period without duodenal MMC activity was markedly longer in short-term, but shorter in long-term (both were significantly longer than in controls). Marked dilatation of the jejunum and reversed jejunal segment was noted across the proximal anastomosis. These results suggest that the transit time and passage of intestinal contents can be delayed and stagnated for at least 10 months after MSBR with a 20-cm reversed jejunal segment. Although, reports on the polarity of peristalsis in the reversed segment in long-term followup have been contradictory in both experimental and clinical studies, this results support the conclusion that the reversed jejunal segment maintains its inherent propagative polarity and pattern over a long postoperative period.

Anastomosis, Surgical↗

Endovascular delivery of vein segments with valves versus direct anastomosis.

PURPOSE: To demonstrate an experimental model designed to allow placement of a vein segment containing a valve into a femoral vein without the need for anastomoses or surgical incision on the target limbs. METHODS: Segments of jugular veins containing valves were harvested bilaterally from 7 female dogs weighing 30 to 40 kg. One of the vein segments was then interposed into one femoral vein, using a standard surgical end-to-end anastomosis. Another segment was loaded into a self-expanding nitinol stent, everted, and secured outside of the stent. This vein-coated stent was then deployed from the jugular approach into the opposite common femoral vein. The endpoint of the study was thrombosis of one of the veins segments or patency at 120 days. The function of the valves was tested prior to completion of the study by instilling dye under incremental pressures and recording the pressure necessary to cause reflux. Light microscopy and electron microscopy were utilized to evaluate structure of the valves at study endpoint. RESULTS: Both grafts in one dog occluded during the second week after surgery. Anastomotic and vein-stented sites remained patent in the remaining 6 animals for 120 days. Retrograde phlebography demonstrated valve competency bilaterally in all cases. The reflux pressures on the stented side averaged 70 mmHg while the transplanted vein segment averaged 55 mmHg. Light microscopy and electron microscopy showed intact vein valve structure in all segments at the completion of the study. CONCLUSIONS: This experimental work demonstrates that endovascular delivery of a native canine vein containing a competent valve is feasible and effective.

Anastomosis, Surgical↗

Adjacent segment degeneration in the lumbar spine.

BACKGROUND: A primary concern after posterior lumbar spine arthrodesis is the potential for adjacent segment degeneration cephalad or caudad to the fusion segment. There is controversy regarding the subsequent degeneration of adjacent segments, and we are aware of no long-term studies that have analyzed both cephalad and caudad degeneration following posterior arthrodesis. A retrospective investigation was performed to determine the rates of degeneration and survival of the motion segments adjacent to the site of a posterior lumbar fusion. METHODS: Two hundred and fifteen patients who had undergone posterior lumbar arthrodesis were included in this study. The study group included 126 female patients and eighty-nine male patients. The average duration of follow-up was 6.7 years. Radiographs were analyzed with regard to arthritic degeneration at the adjacent levels both preoperatively and at the time of the last follow-up visit. Disc spaces were graded on a 4-point arthritic degeneration scale. Correlation analysis was used to determine the contribution of independent variables to the rate of degeneration. Survivorship analysis was performed to describe the degeneration of the adjacent motion segments. RESULTS: Fifty-nine (27.4%) of the 215 patients had evidence of degeneration at the adjacent levels and elected to have an additional decompression (fifteen patients) or arthrodesis (forty-four patients). Kaplan-Meier analysis predicted a disease-free survival rate of 83.5% (95% confidence interval, 77.5% to 89.5%) at five years and of 63.9% (95% confidence interval, 54.0% to 73.8%) at ten years after the index operation. Although there was a trend toward progression of the arthritic grade at the adjacent disc levels, there was no significant correlation, with the numbers available, between the preoperative arthritic grade and the need for additional surgery. CONCLUSIONS: The rate of symptomatic degeneration at an adjacent segment warranting either decompression or arthrodesis was predicted to be 16.5% at five years and 36.1% at ten years. There appeared to be no correlation with the length of fusion or the preoperative arthritic degeneration of the adjacent segment.

Adolescent↗

Focal sparing of segment IV in fatty livers shown by sonography and CT: correlation with aberrant gastric venous drainage.

OBJECTIVE: One of the most common sites of focal sparing in fatty livers (focal spared area) shown by sonography or CT is the posterior edge of segment IV. The differentiation of such a focal spared area from tumor has been a diagnostic challenge. The purpose of this study was to determine if a correlation exists between the focal spared area at the posterior edge of segment IV in fatty liver and the decrease of portal perfusion from the main portal vein due to aberrant gastric venous drainage directed into segment IV. SUBJECTS AND METHODS: Seventeen patients with fatty liver diagnosed on the basis of sonographic and CT findings who had hepatic arteriography and/or CT during arterial portography (CTAP) were included in the study. Seven patients had a focal spared area more than 2 cm in the longest diameter at the posterior edge of segment IV, and 10 patients did not have a focal spared area. The frequency of aberrant gastric venous drainage shown by arteriography (17 patients) and/or by CTAP (15 patients) was compared in the two groups of patients. RESULTS: Hepatic arteriography showed aberrant gastric venous drainage in all patients who had a spared area, and CTAP showed a portal perfusion defect at the posterior edge of segment IV in all five patients with a focal spared area who underwent CTAP. On the other hand, no definite aberrant gastric venous drainage and portal perfusion defect were seen in any patient without a spared area. The difference in the frequency of aberrant gastric venous drainage between the two groups of patients was statistically significant (chi-square test, p < .0001). CONCLUSION: Our results show that a strong correlation exists between the focal spared area at the posterior edge of segment IV in fatty liver and aberrant gastric venous drainage directed to segment IV. Focally decreased blood flow from the main portal vein associated with aberrant gastric venous drainage is a likely cause of the focal spared area. This fact is important for the differential diagnosis of hepatic tumors.

Adult↗

Creation of a three-dimensional model of human segmental lung anatomy.

OBJECTIVE: The investigation of pulmonary embolism using scintigraphic tomography requires a model of the internal architecture of the segments and subsegments in the human lung. Such a model has been developed by the segmentation and subsegmentation of an existing whole-body tissue-segmented phantom. MATERIALS AND METHODS: By using information from suitably windowed human axial CT scans, combined with the information gained from the injection of color-coded dyes into the segmental bronchi of human cadaveric lungs, the lobar and segmental boundaries were added to the existing phantom. Further refinements were added from reports in the literature regarding the predominant pattern of subsegmental bronchi in a series of human cadavers, enabling the creation of subsegmental boundaries. RESULTS: A digitized model of the segmental and subsegmental anatomy of the human lung was successfully created. External, or pleural, projections of the complex internal arrangement of the segments closely corresponded with the projections of the best available authorities on the subject. CONCLUSION: The model provides the opportunity to address several issues germane to scintigraphy and important for diagnosing pulmonary embolic disease. In particular, the model allows the manipulation of three-dimensional data sets to explore issues of importance to tomographic lung scanning.

Computer Simulation↗