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The Drosophila kismet gene is related to chromatin-remodeling factors and is required for both segmentation and segment identity.

The Drosophila kismet gene was identified in a screen for dominant suppressors of Polycomb, a repressor of homeotic genes. Here we show that kismet mutations suppress the Polycomb mutant phenotype by blocking the ectopic transcription of homeotic genes. Loss of zygotic kismet function causes homeotic transformations similar to those associated with loss-of-function mutations in the homeotic genes Sex combs reduced and Abdominal-B. kismet is also required for proper larval body segmentation. Loss of maternal kismet function causes segmentation defects similar to those caused by mutations in the pair-rule gene even-skipped. The kismet gene encodes several large nuclear proteins that are ubiquitously expressed along the anterior-posterior axis. The Kismet proteins contain a domain conserved in the trithorax group protein Brahma and related chromatin-remodeling factors, providing further evidence that alterations in chromatin structure are required to maintain the spatially restricted patterns of homeotic gene transcription.

Amino Acid Sequence↗

Prediction of inter-segment stability and osteophyte formation on the multi-segment C2-C7 after unilateral and bilateral facetectomy.

The objective of this study was to determine the intersegment stability, disc degeneration, and osteophytes formation on the multisegment cervical spine (C2-C7) after unilateral and bilateral facetectomy. A geometrically accurate non-linear three-dimensional model of the intact human cervical spine was created from the digitized coordinates of the dry vertebrae. The intact model was validated against the published results under physiological loading conditions. Eight surgically altered models were created from the intact model. The intact and surgical altered models were subjected to physiological loading. The inclusion of five levels in the present model allowed accurate determination of the intersegment responses and internal cortical bone and disc annulus stress in the adjacent spinal components. Results indicated that facetectomy performed on C5-C6 significantly affects the corresponding stress and intersegment motions at the corresponding C5-C6 levels. The maximum increases were 18 per cent for bilateral facetectomy and 7 per cent for unilateral facetectomy under lateral bending. Combined flexion-extension and axial rotation caused an approximately similar amount of increases after total facetectomy. In addition, adjacent segments (C4-C5 and C6-7) also experience a slight increase in the intersegment responses and internal stress after facetectomy. It has been shown that facetectomy of greater than 50 per cent resulted in segment hypermobility and substantial increase in the disc annulus and cortical bone stress. Increase in the stress may lead to osteophytes formation. This study revealed important information that will help clinicians identify the critical intersegment stability and to decide on the amount of facets resection.

Cervical Vertebrae↗

State-dependent cross-linking of the M2 and M3 segments: functional basis for the alignment of GABAA and acetylcholine receptor M3 segments.

Construction of a GABAA receptor homology model based on the acetylcholine (ACh) receptor structure is complicated by the low sequence similarity between GABAA and ACh M3 transmembrane segments that creates significant uncertainty in their alignment. We determined the orientation of the GABAA M2 and M3 transmembrane segments using disulfide cross-linking. The M2 residues alpha1M266 (11') and alpha1T267 (12') were mutated to cysteine in either wild type or single M3 cysteine mutant (alpha1V297C, alpha1A300C to alpha1A305C) backgrounds. We assayed spontaneous and induced disulfide bond formation. Reduction with DTT significantly potentiated GABA-induced currents in alpha1T267C-L301C and alpha1T267C-F304C. Copper phenanthroline-induced oxidation inhibited GABA-induced currents in these mutants and in alpha1T267C-A305C. Intrasubunit disulfide bonds formed between these Cys pairs, implying that the alpha-carbon separation was at most 5.6 A. The reactive alpha1M3 residues (L301, F304, A305) lie on the same face of an alpha-helix. The unresponsive ones (A300, I302, E303) lie on the opposite face. In the resting state, the reactive side of alpha1M3 faces M2-alpha1T267. In conjunction with the ACh structure, our data indicate that alignment of GABAA and ACh M3 requires a single gap in the GABAA M2-M3 loop. In the presence of GABA, oxidation of alpha1T267C-L301C and alpha1T267C-F304C had no effect, but oxidation of alpha1T267C-A305C caused a significant increase in spontaneous channel opening. We infer that, as the channel opens, the distance and/or orientation between M2-alpha1T267 and M3-alpha1A305 changes such that the disulfide bond stabilizes the open state. This begins to define the conformational motion that M2 undergoes during channel opening.

Amino Acid Sequence↗

Role of external pallidal segment in primate parkinsonism: comparison of the effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism and lesions of the external pallidal segment.

These experiments re-examined the notion that reduced activity in the external pallidal segment (GPe) results in the abnormalities of neuronal discharge in the subthalamic nucleus (STN) and the internal pallidal segment (GPi) and in the development of parkinsonian motor signs. Extracellular recording in two rhesus monkeys, which had been rendered parkinsonian by treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), revealed that the average neuronal discharge rate decreased in GPe but increased in STN and GPi. After MPTP, neurons in all three nuclei tended to discharge in oscillatory bursts. In addition, GABA release in STN (measured with microdialysis) was reduced, indicative of reduced activity along the GPe-STN pathway. Finally, the concentration of glutamic acid dehydrogenase (GAD; measured with autoimmunoradiography) was increased in GPe and GPi, likely reflecting increased striatal input and increased activity of local axon collaterals, respectively. Surprisingly, GAD protein in STN remained unchanged, indicating that the usual assumption that GAD levels are determined primarily by the overall activity of GABAergic elements may be too simplistic. The results from the MPTP-treated animals were compared with results obtained in a second group of three animals with ibotenic acid lesions of GPe. GPe lesions resulted in increased discharge in STN and GPi, comparable with the changes seen after MPTP but did not induce oscillatory bursting and had no behavioral effects. The results indicate that a mere reduction of GPe activity does not produce parkinsonism. Other changes, such as altered discharge patterns in STN and GPi, may play an important role in the generation of parkinsonism.

Action Potentials↗

Aneurysm rupture at an anomalous collateral artery that extended from the proximal A2 segment to the middle of the M1 segment, bypassing atresia of the internal carotid artery bifurcation. Case report.

The authors report the first known case in which an anomalous collateral artery was found to connect the proximal A2 segment with the middle of the M1 segment. This rarity was associated with atresia of the T-shaped internal carotid artery bifurcation. Two aneurysms had developed on a tortuous and tangled portion of the anomalous artery; one of them had ruptured, producing a subarachnoid hemorrhage and an intracerebral hematoma in the area of the putamen. The aneurysms were clipped and the intracerebral hematoma was removed via an emergency craniotomy. Possible causes of the anomaly and the differences between it and accessory and duplicated middle cerebral arteries are reviewed.

Aged↗

Large lower segment myoma--myomectomy at lower segment caesarean section--a report of two cases.

Uterine leiomyoma is found in approximately 2% of pregnant women. One in ten women will have complications related to myoma in pregnancy. Myomectomy during pregnancy especially at Caesarean section is much discouraged in the literature. We present here 2 cases of large uterine myoma, situated in the anterior aspect of the lower segment, complicating pregnancy at term. Myomectomy in both instances allowed delivery of the fetus through the lower segment, making vaginal delivery in subsequent pregnancies possible.

Adult↗

Severity of coronary artery disease in patients with acute coronary syndrome without ST segment elevation is related to baseline troponin I and ST-segment depression.

BACKGROUND: Risk assessment for patients admitted with acute coronary syndrome (ACS) is usually based on the past medical history, along with several clinical and biochemical criteria. We hypothesised that stratification of patients with ACS according to the presence of ST-segment depression and results of a qualitative troponin I test would identify subjects with more severe disease who may benefit from an earlier, more aggressive strategy. MATERIAL/METHODS: The study group consisted of 115 patients hospitalized for typical chest pain (>5 min) occurring within the last 24 hours, with coronary angiography. Blood was drawn for routine biochemistry and qualitative troponin I testing, and ECG was performed on admission. RESULTS: Patients were classified according to the presence of ST segment depression (ST) and the troponin I test results (T) into three categories: group A, consisting of 34 patients with ST+/T+; group B, consisting of 84 patients with either ST+/T- or ST-/T+; and group C, consisting of 7 subjects with ST-/T-. This stratification correlated significantly with the extent of coronary artery disease (p=0.0004). Significant coronary artery stenosis was significantly more prevalent in patients from groups A and B than in C (p<0.002). No difference in the patients' medical history, apart from more frequent AMI within the past 10 days in group A (p=0.009) was found between groups. CONCLUSIONS: Admission assessment of ECG and troponin I tests in patients with ACS may identify subjects with significant coronary artery disease, who are at high risk and could benefit from aggressive therapy.

Acute Disease↗

Postoperative changes in remnant medial segment parenchyma of living donor livers after procurement of left lateral segment graft.

BACKGROUND/AIMS: Procurement of left lateral segment (LLS) graft usually resulted in uneventful atrophy of the remnant medial segment parenchyma (RMSP) in living donors, but duct dilatation was often detected in the RMSP. We tried to clarify the postoperative atrophic sequences of the RMSP. METHODOLOGY: We analyzed clinical profiles of 33 LLS graft donors out of 362 living donors from January 2002 to December 2003. LLS grafts were divided into type 1 (classical LLS, n= 18), type 2 (intermediately extended LLS, n=8), and type 3 (extended LLS similar to left lobe without middle hepatic vein trunk, n= 7). RESULTS: On 1-week dynamic computed tomography, early extensive hyperattenuation indicating interlobar arterial collaterals (ILAC) was observed in 4 (22.2%) donors of type 1 and 2 (25%) donors of type 2 LLS grafts. Peak values of serum liver enzymes were not correlated with the amount of RMSP, but they were exceptionally elevated on poor development of ILAC. Most of RMSP became atrophied within 3 months. Delayed-onset bile leak occurred in a donor, by which we had to resect his functional RMSP after 3 months. ILAC was highly associated with persistent bile production and slow atrophic change at RMSP after LLS graft donation. CONCLUSIONS: These data suggested that temporary arterial collateral formation worked as a buffering mechanism leading to slow and uneventful degeneration of inflow-deprived hepatic parenchyma.

Adult↗

[Value of segmental systolic pressure determination in the diagnosis and selection of reconstructive operations of the aorto-ileo-femoral segments].

The segmentary systolic pressure along the lower extremities was studied by means of ultrasonic dopplerosphygmomanometry in patients with isolated and associated lesions of the aorto-ileo-femoral segment. The possibility to investigate the hemodynamic significance of stenotic lesions of the arteries is shown which is of value for choice of the method of reconstructive operations in associated lesions of the aorto-ileo-femoral segment.

Aortic Diseases↗

Metal-tetracycline/H+ antiporter of Escherichia coli encoded by transposon Tn10. The structural resemblance and functional difference in the role of the duplicated sequence motif between hydrophobic segments 2 and 3 and segments 8 and 9.

The properties of site-directed mutants as to the putative hydrophilic loop region between hydrophobic segments 2 and 3 in the transposon Tn10-encoded metal-tetracycline/H+ antiporter (TET) were reported in our previous paper (Yamaguchi, A., Someya, Y., and Sawai, T. (1992) J. Biol. Chem. 267, 19155-19162). The loop between hydrophobic segments 8 and 9 contains a conserved sequence motif, GXXXXKXGEK, which is a derivative of the sequence motif, GXXXXRXGRR, in loop2-3. Site-directed mutagenesis studies on loop8-9 revealed that the two loops exhibit significant structural resemblance, that is, 1) when the Gly residue at the eighth position in each loop was replaced by various amino acid residues, the residual activity of the resultant mutants corresponded well to the beta-turn propensity of the substituent, 2) the Cys mutant as to the fourth position in each loop was most profoundly inactivated by N-ethylmaleimide among 10 Cys mutants as to each loop, and 3) the reactivity of a Cys residue introduced at the third position in loop8-9 with N-ethylmaleimide was lower than that in the case of the other Cys mutants, probably due to the residue being partially cryptic as to the attack of the reagent, similar to in the case of the corresponding residue in loop2-3, the latter being entirely cryptic. The Gly at the first position in loop8-9 is less important than the corresponding Gly in loop2-3, however, since the TET protein suffered a loss of activity when a bulky side chain was introduced at the first position in loop8-9 as well as in loop2-3, the structural roles of the 2 glycines are likely to be similar. These findings suggested that loop2-3 and loop8-9 may occupy similar positions in the three-dimensional structure of the TET protein. On the other hand, the two loops showed a significant functional difference; the negative charge of Asp66 and the positive charge of Arg70 in loop2-3 were essential for the transport function, but, in contrast, there was no functionally essential residue in loop8-9, indicating that loop2-3 may form an "active" leaflet in the TET protein, while loop8-9 may be a "silent" counterpart.

Amino Acid Sequence↗

Clinical and genetic heterogeneity in familial focal segmental glomerulosclerosis. International Collaborative Group for the Study of Familial Focal Segmental Glomerulosclerosis.

BACKGROUND: Familial forms of focal segmental glomerulosclerosis (FFSGS) that exhibit autosomal dominant or recessive patterns of inheritance have been described. The genetic basis of these hereditary forms of FSGS is unknown. One recent study of a kindred from Oklahoma with an autosomal dominant form of FSGS linked this disease to a region of chromosome 19q. In addition, polymorphisms in a gene in this region on chromosome 19q13 have been linked to congenital nephrotic syndrome of the Finnish type. We have ascertained and characterized a large family with autosomal dominant FFSGS (Duke 6530). METHODS: Families were compared for clinical and genetic heterogeneity. To test for linkage of our family to this portion of chromosome 19, genomic DNA was isolated from 102 family members, and polymerase chain reaction was performed using eight microsatellite markers that spanned the area of interest on chromosome 19. Data were evaluated using two-point linkage analysis, multipoint analysis, and an admixture test. RESULTS: Linkage was excluded at a distance of +/- 5 to 10 CM for all markers tested with two-point log10 of the odds of linkage (LOD) scores and from an approximate 60 CM interval in this area of chromosome 19q via multipoint analysis. CONCLUSIONS: FSGS has been called the "final common pathway" of glomerular injury, as it is a frequent pathological manifestation with diverse etiologies. This diversity likely correlates with the genetic heterogeneity that we have established. Thus, our data demonstrate that there are at least two genes responsible for this disease, and there is genetic as well as clinical heterogeneity in autosomal dominant FSGS.

Adolescent↗

The application of electron microscopic morphometry as helpful method in the diagnosis of focal segmental glomerulosclerosis (FSGS) early phase. I. Morphometric electron microscopic studies of renal glomeruli in cases of focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD) and mesangioproliferative glomerulonephritis (GNMES) in children.

Electron microscopy morphometric studies were carried out on material obtained from children with minimal change disease (MCD), mesangioproliferative glomerulonephritis (GNMES) and focal segmental glomerulosclerosis (FSGS). The results indicated that an increase in the volume of the matrix in mesangioproliferative glomerulonephritis was due to an increase in the number of cells. The amount of produced matrix in mesangioproliferative glomerulonephritis was proportional to the number of cells in mesangium (so there is no overproduction of matrix). The ratios of mesangial matrix volume to cell volume and matrix volume to the volume of the entire mesangial region in MCD and GNMES were similar and differed significantly from the ratios found in FSGS. The present findings indicate that morphometric studies may be useful in the early diagnosis of glomerular sclerosis. This is particularly significant in cases where light microscopic examination fails to reveal changes indicative of glomerular sclerosis.

Child, Preschool↗

Twenty-seven children with focal segmental glomerulosclerosis: correlation between the segmental location of the glomerular lesions and prognosis.

Twenty-seven children with focal segmental glomerulosclerosis (FSGS) were studied for clinical and pathological manifestations in order to determine whether the location of the sclerotic lesions bears prognostic implications. There were 11 children with peripheral FSGS and 16 with hilar FSGS. During a mean follow-up period of 6 years, 10 of the 16 with hilar FSGS developed renal failure (GFR less than 20 ml/min/m2) but all of the 11 with peripheral FSGS maintained normal renal function. We suggest that FSGS may be divided into a hilar type with poor prognosis and a peripheral type with benign prognosis. It is conceivable that these two groups represent etiologically different entities.

Adolescent↗

Quality of care by classification of myocardial infarction: treatment patterns for ST-segment elevation vs non-ST-segment elevation myocardial infarction.

BACKGROUND: Practice guidelines for acute ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) recommend similar therapies and interventions, but differences in patterns of care between MI categories have not been well described in contemporary practice. METHODS: In-hospital treatments with similar recommendations from practice guidelines were compared with outcomes in 185 968 eligible patients (without listed contraindications) with STEMI (n = 53 417; 29%) vs NSTEMI (n = 132 551; 71%) from 1247 US hospitals participating in the National Registry of Myocardial Infarction 4 between July 1, 2000, and June 30, 2002. Hierarchical logistic regression modeling was used to determine adjusted differences in treatment patterns in MI categories. RESULTS: Unadjusted in-hospital mortality rates were high for NSTEMI (12.5%) and STEMI (14.3%), and the use of guideline-recommended medications and interventions was suboptimal in both categories of patients with MI. The adjusted likelihood of receiving early (within 24 hours of presentation) aspirin, beta-blockers, and angiotensin-converting enzyme inhibitors was higher in patients with STEMI. Similar patterns of care were noted at hospital discharge: the adjusted likelihood of receiving aspirin, beta-blockers, angiotensin-converting enzyme inhibitors, lipid-lowering agents, smoking cessation counseling, and cardiac rehabilitation referral was higher in patients with STEMI. CONCLUSIONS: Evidence-based medications and lifestyle modification interventions were used less frequently in patients with NSTEMI. Quality improvement interventions designed to narrow the gaps in care between NSTEMI and STEMI and to improve adherence to guidelines for both categories of patients with MI may reduce the high mortality rates associated with acute MI in contemporary practice.

Aged↗

Effect of hydrophilic soft segment side chains on the surface properties and blood compatibility of segmented poly(urethaneureas).

Segmented poly(urethaneureas) with hydrophilic side chains were prepared from poly(tetramethylene oxide) (PTMO), 4,4'-diphenylmethane diisocyanate (MDI), ethylene diamine (ED) and a diol with a long hydrophilic side chain comprised of an ethylene oxide-proplene oxide copolymer. The end groups of the hydrophilic chains were either sodium sulfonate or methoxy groups. The state of microphase separation showed a small dependence on the fraction of long-chain hydrophilic diol. Surface analysis by means of static underwater contact angle and dynamic contact angle measurements revealed that the graft chains were at the aqueous interface in the hydrated state. An ex vivo A-V shunt experiment revealed that a more thrombogenic blood-material response was correlated with an increase in the concentration of polymeric hydrophilic side chain incorporation. The polyurethane containing a long chain diol with methoxy end groups exhibited a higher level of thrombogenicity than the similar polymers possessing a sulfonate terminated side chain.

Animals↗

The M2 gene segment is involved in the capacity of reovirus type 3Abney to induce the oily fur syndrome in neonatal mice, a S1 gene segment-associated phenotype.

Oral inoculation of reovirus type 3 Abney (T3A) into neonatal mice induces hepatitis and the biliary atresia-associated oily fur syndrome (OFS), a phenotype previously linked to the S1 gene. We found that following oral inoculation, none of three T3A mutants, JH2, JH3, and JH4, containing different single amino acid substitutions in the M2 gene, induced the OFS or extensive liver necrosis. Similarly, reassortant viruses containing both a JH4-S1 and a JH4-M2 gene segment did not induce the OFS, whereas another reassortant containing a JH4-S1 gene and a M2 gene from reovirus type 3 Dearing fully recovered this capacity. Together, these results constitute the first evidence for the involvement of the M2 gene in the S1 gene-associated capacity of T3A to induce hepatobiliary disease in neonatal mice.

Animals↗

Clinical studies on high and low power laser radiation upon some structures of the anterior and posterior segments of the eye. Experiences in the treatment of some pathological conditions of the anterior and posterior segments of the human eye by means of a Nd:YAG laser, driven at various power levels.

A Q-switched Nd:YAG laser apparatus has been used in the treatment of a number of pathological conditions of the anterior and posterior segments of the human eye. This laser system may be driven in a free running mode, thereby allowing variation of pulse duration over a range of 12 ns to 10 ms. With increasing pulse duration, non-linear mechanical damage patterns characteristic of the biological effects at the lower exposure duration range become unimportant when compared to the so-called thermal effects met at the upper pulse duration range. The thermal damage mechanisms may be useful when applied together with the mechanical damage mechanism, for instance when iris perforations are intended. Because the Wise-Witter irradiation method for the treatment of open angle glaucoma depends on low power, thermal mechanisms, this instrument may also be useful for the treatment of this disease entity. This same irradiation mode may also be applied to at least some irradiation tasks of the retina and choroid.

Choroid↗