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PubMed1999

Evaluation of microvascularization pattern visibility in human choroidal melanomas: comparison of confocal fluorescein with indocyanine green angiography.

BACKGROUND: The presence of specific microvascularization patterns (networks, parallel with and without crosslinking, silent) in histological sections of human choroidal melanomas has prognostic significance for survival. We showed previously in selected patients that the identification of these microvascularization patterns is possible in vivo by using confocal scanning laser indocyanine green angiography and that this technique is superior to fluorescein angiography using a conventional acquisition technique with a fundus camera. We now routinely use simultaneous confocal fluorescein/indocyanine green angiography to study microvascularization patterns in choroidal melanomas. The purpose of this study was to compare the visibility of tumor vessels and microvascularization patterns in fluorescein and indocyanine green angiography in simultaneous confocal series taken with the same instrument in a large prospective series of patients. PATIENTS AND METHODS: The simultaneously procured confocal fluorescein and indocyanine green angiograms of 50 patients with untreated choroidal melanomas (maximal apical height according to standardized A-scan between 2 and 8 mm) were studied for the visibility of tumor vessels and microvascularization patterns. At least one simultaneous confocal optical series (32 images in sequential depth order) during the early arterial venous phase was obtained per patient. RESULTS: Confocal forescein angiography disclosed signs of tumor vascularization in 12 (24%) of the 50 patients examined. However, in only 3 patients (6%) could microvascularization patterns be identified using confocal fluorescein angiography, and only in the very early arterial phase, which is often difficult to capture. In contrast, simultaneously obtained confocal indocyanine green angiograms disclosed tumor vessels in 47 (94%) of the examined 50 patients and microvascularization patterns could be identified in all of these cases. In 3 patients (6%) no tumor vessels could be detected within the tumor borders. CONCLUSION: This study demonstrates that confocal indocyanine green angiography images microvascularization patterns in choroidal melanomas better than fluorescein angiography, even when the images are acquired with the same technique. This can be explained with the different absorption, fluorescence and exudation characteristics of these dyes. In vivo imaging of these microvascularization patterns using confocal indocyanine green angiography offers the possibility of assessing the prognosis of choroidal melanomas without the removal of tissue.

Adult↗
PubMed2003

Difference in cytoplasmic localization pattern of neutral mucin among lobular endocervical glandular hyperplasia, adenoma malignum, and common adenocarcinoma of the uterine cervix.

To investigate whether the cytoplasmic localization pattern of neutral mucin differs between lobular endocervical glandular hyperplasia (LEGH) and cervical adenocarcinoma (CxAd), including minimal-deviation adenocarcinoma (MDA), or adenoma malignum, alcian blue (pH 2.5)/periodic acid-Schiff (AB-PAS) staining was performed to formalin-fixed paraffin-embedded tissue sections of 13 lesions of LEGH and 53 tumors of CxAd, including 6 tumors of MDA. The cytoplasmic localization of neutral mucin was classified as a "whole cytoplasmic pattern," in which neutral mucin filled the cytoplasm entirely, or as an "apical pattern," in which neutral mucin was localized in the subsurface area only. Cytoplasmic neutral mucin patterns were detected in all 13 cases of LEGH and in 19 cases (36%) of CxAd, including five cases of MDA. The localization of neutral mucin was always the whole cytoplasmic pattern in 13 cases of LEGH, but was the apical pattern in these 19 cases of CxAd. The other 34 cases of CxAd, including 1 case of MDA, corresponded to the acid mucin pattern stained purple or blue or no staining pattern by AB-PAS. Among the 53 cases of CxAd, the apical neutral mucin pattern was an indicator of poorer patient prognosis by univariate and multivariate analyses. The examination of cytoplasmic localization of neutral mucin might be applicable, not only to differential diagnosis between LEGH and CxAd, including MDA, but also to estimate clinical aggressiveness of CxAd.

Adenocarcinoma↗
PubMed2005

Growth pattern and distribution of follicular dendritic cells in mantle cell lymphoma: a clinicopathological study of 96 patients.

Mantle cell lymphoma (MCL) is an aggressive lymphoma with accepted risk factors such as proliferation markers. To date, the different follicular dendritic cell (FDC) patterns have never been analyzed in comparison with the overall survival time. Lymph node biopsy specimens from 96 patients were analyzed by conventional morphology and immunohistochemistry with antibodies against cluster differentiation (CD)20, CD5, CD23, cyclin D1, and FDC (Ki-M4P). Two groups can be distinguished with different FDC patterns: a nodular pattern in 79 cases and a diffuse pattern in 17 cases. A Kaplan-Meier analysis revealed significantly better survival for the nodular group (p=0.0312). This group was subdivided into a group with a nodular FDC pattern similar to the FDC distribution in primary follicles (PF-nodular in 72 cases) and one with a nodular FDC pattern resembling the colonization of germinal centers (GCs) by tumor cells (GC-nodular in seven cases). A Kaplan-Meier analysis showed that patients with MCL with a PF-nodular FDC pattern had a significantly better clinical outcome than patients with the other two patterns (p=0.0033). If only cases with classical cytology (n=79) were analyzed (blastoid types excluded), patients with a PF-nodular FDC pattern had a better clinical outcome (p=0.0008). The distribution of FDC in MCL is a diagnostic tool for identifying patients with a better clinical prognosis.

Antigens, CD20↗
PubMed2000

Fluctuation patterns of HCV-RNA serum level in patients with chronic hepatitis C.

The serum level of hepatitis C virus (HCV)-RNA is clinically important as a predictor of the response to interferon (IFN) therapy in patients with chronic hepatitis C. If serum HCV-RNA levels fluctuate during follow-up, and IFN therapy is begun at the time of a low HCV-RNA level, the IFN therapy may be more effective. We evaluated the fluctuation of HCV-RNA serum levels for 2 years in 212 patients with chronic hepatitis C, untreated with IFN who had HCV genotype 1b and an HCV-RNA level of 10 Meq/ml or more at first consultation. The HCV-RNA level was measured monthly for 2 years with an HCV branched DNA probe assay (b DNA probe assay). We classified HCV-RNA patterns into three types by the ratio of maximum HCV-RNA level (a) to minimum HCV-RNA level (b). In pattern 1 (constant type, 151 patients; 71.2%) the a/ b ratio was 1-5. In pattern 2 (slight fluctuation type, 46 patients; 21.7%) the a/b ratio was 5-10. In pattern 3 (severe fluctuation type, 15 patients; 7.1%), the a/b ratio was 10 or more. Next, we evaluated the factors associated with the three patterns. Acute exacerbation of chronic hepatitis was regarded as an increase in serum alanine aminotransferase (ALT) level to more than 250 IU/l. The incidence of acute exacerbation for a 2-year follow-up was 13.9% (21/151) in pattern 1, 19.6% (9/46) in pattern 2, and 53.3% (8/15) in pattern 3. Multivariate analysis showed that acute exacerbation was the most important factor in the manifestation pattern 3. In conclusion, we found that: (1) about 70% of patients had a constant HCV-RNA levels for 2 years. (2) A few patients had severe fluctuation of serum HCV-RNA level after acute exacerbation of chronic hepatitis.

Adult↗
PubMed2004

Utility of age, gender, ANA titer and pattern as predictors of anti-ENA and -dsDNA antibodies.

Monovariate and multivariate analyses including logistic regression were performed to determine associations among predicting variables [age, gender, immunofluorescence pattern, and anti-nuclear antibody (ANA) titer] and anti-extractable nuclear antigen (ENA) and -dsDNA antibodies (Abs) in 1089 patients with positive fluorescent ANA (FANA) test results. Samples with high titer ANAs had an increased frequency of anti-ENA and -dsDNA Abs. The receiver operating (ROC) curves of the ANA titer for anti-ENA Abs had a larger under the curve area compared to the ROC curve for anti-dsDNA Abs, indicating that ANA titer is better for predicting anti-ENA Abs than anti-dsDNA Abs. There was no relation noticed between immunofluorescence patterns and anti-ENA and -dsDNA Abs except an increased frequency of anti-dsDNA Abs found in samples with a homogeneous pattern. Probability calculations on the basis of the ANA pattern and the titer showed that samples with low titer ANAs (1:160 or less) had low probabilities for anti-ENA Abs (0.002-0.009) regardless of immunofluorescence patterns. However, samples with a homogeneous pattern at any titers including low titers had high probabilities for anti-dsDNA Abs. A decreased frequency of anti-dsDNA Abs as measured by Crithidia assay was noticed in samples from patients aged 50 or older. In contrast, no association was noticed between age and anti-ENA Abs. There was no female preponderance found in the presence of anti-ENA and -dsDNA Abs. In conclusion, our study shows that the ANA titer but not the immunofluorescence pattern is useful in predicting anti-ENA Abs. In contrast, both the ANA titer and the immunofluorescence pattern help in predicting anti-dsDNA Abs. Samples with low titer ANAs (1:160 or less) may not need a further test for anti-ENA Abs unless an ANA-associated disease is highly suspected. However, a test for anti-dsDNA Abs should be considered in samples with a homogeneous pattern at any titer including low titers.

Adult↗
PubMed2005

Patterns of surveillance practices after curative surgery for colorectal cancer in a French population.

PURPOSE: Despite controversies, postoperative surveillance of colorectal cancer is generally recommended. This registry-based study was designed to assess the adherence of surveillance practices to French guidelines and identify three-year surveillance patterns and their demographic and clinical determinants. METHODS: All patients (N = 409) diagnosed with first colorectal cancer in 1998 and alive without recurrence at least six months after curative surgery were identified from a population-based registry. Medical charts from multiple sources were reviewed to collect exhaustive information on follow-up procedures used during a three-year period. Multiple correspondence and cluster analyses were used to identify surveillance patterns. RESULTS: The proportion of patients with a lower surveillance than that recommended was 35 percent for clinical examination, 65 percent for abdominal ultrasound, 52 percent for chest x-ray, and 20 percent for colonoscopy. Cluster analysis identified three patterns called minimal, moderate, and intensive surveillance patterns, which included 47, 24, and 29 percent of the patients respectively. The main independent predictors of both moderate and intensive surveillance patterns vs. minimal pattern were advanced tumor stage, chemotherapy, and radiation therapy. Younger age also was strongly associated with the intensive surveillance pattern, and the presence of symptoms with the moderate surveillance pattern. CONCLUSIONS: Adherence of surveillance practices to French guidelines seems relatively poor. Surveillance patterns are mainly explained by patient age, tumor stage, and treatment modalities.

Aged↗
PubMed2005

The possible role of spike patterns in cortical information processing.

When the same visual stimulus is presented across many trials, neurons in the visual cortex receive stimulus-related synaptic inputs that are reproducible across trials (S) and inputs that are not (N). The variability of spike trains recorded in the visual cortex and their apparent lack of spike-to-spike correlations beyond that implied by firing rate fluctuations, has been taken as evidence for a low S/N ratio. A recent re-analysis of in vivo cortical data revealed evidence for spike-to-spike correlations in the form of spike patterns. We examine neural dynamics at a higher S/N in order to determine what possible role spike patterns could play in cortical information processing. In vivo-like spike patterns were obtained in model simulations. Superpositions of multiple sinusoidal driving currents were especially effective in producing stable long-lasting patterns. By applying current pulses that were either short and strong or long and weak, neurons could be made to switch from one pattern to another. Cortical neurons with similar stimulus preferences are located near each other, have similar biophysical properties and receive a large number of common synaptic inputs. Hence, recordings of a single neuron across multiple trials are usually interpreted as the response of an ensemble of these neurons during one trial. In the presence of distinct spike patterns across trials there is ambiguity in what would be the corresponding ensemble, it could consist of the same spike pattern for each neuron or a set of patterns across neurons. We found that the spiking response of a neuron receiving these ensemble inputs was determined by the spike-pattern composition, which, in turn, could be modulated dynamically as a means for cortical information processing.

Action Potentials↗
PubMed1992

Multiday driving patterns and motor carrier accident risk: a disaggregate analysis.

A method has been developed to estimate the relative accident risk posed by different patterns of driving over a multiday period. The procedure explicitly considers whether a driver is on duty or off duty for each half hour of each day during the period of analysis. From a data set of over 1,000 drivers, nine distinct driving patterns are identified. Membership in the patterns is determined exclusively by the pattern of duty hours for seven consecutive days; for some drivers an accident occurred on the eighth day while others had no accident, therefore each pattern can be associated with a relative accident risk. Additional statistical modeling allowed the consideration, in addition to driving pattern, of driver age, experience with the firm, hours off duty prior to the last trip and hours driving on the last trip (either until the accident or successful completion of the trip). The finding of the modeling is that driving patterns over the previous seven days significantly affect accident risk on the eighth day. In general, driving during the early and late morning (e.g., midnight to 10 A.M.) has the highest accident risk while all seven other multiday patterns had indistinguishable risk. Consecutive hours driven also has a significant effect on accident risk: the first hour through the fourth hour having the lowest risk with a fluctuating increase in risk to a maximum beyond nine hours. Driver age and hours off duty immediately prior to a trip do not appear to affect accident risk significantly. These findings quantitatively assess the relative accident risk of multiday driving patterns using data from actual truck operations. Further research is recommended in the areas of refining model structures, adding explanatory variables (such as highway type), and testing more complex models.

Accidents, Occupational↗
PubMed1979

Doughnut pattern of technetium-99m pyrophosphate myocardial uptake in patients with acute myocardial infarction: a sign of poor long-term prognosis.

Thirty survivors of acute myocardial infarction with 3+ or 4+ positive technetium-99m pyrophosphate myocardial scintigrams were followed up for 28 +/- 3.1 months (mean +/- standard deviation). Three patient groups were identified from the pattern of radioactive uptake in the scintigram: Group I, 16 patients with focal uptake (anterior in 7, lateral in 2, posterior in 3 and inferior in 4); Group II, 6 patients with anterior myocardial infarction and a doughnut pattern of uptake; Group III, 8 patients with nontransmural myocardial infarction and a diffuse pattern of uptake. Late complications developed in all patients with the doughnut pattern of uptake compared with 43 percent of patients with the focal pattern and 12 percent of patients with the diffuse pattern. After discharge from the hospital, five of six patients with a doughnut pattern of uptake died (mean survival time 9.8 months after the initial myocardial infarction). This mortality rate (83 percent) was significantly greater than that of patients with a focal (mortality rate 6 percent) or diffuse (no mortality) pattern of uptake. The doughnut pattern of technetium-99m pyrophosphate myocardial uptake in patients with acute myocardial infarction appears to identify a subgroup of patients with a very poor long-term prognosis.

Angina Pectoris↗
PubMed1987

Time structure and stimulus dependence of precisely replicating patterns present in monkey cortical neuronal spike trains.

Evidence is presented on the parameters that affect the occurrence of precisely replicating patterns of neural discharge present as 'hidden' patterns in individual neuronal discharge trains of the visual cortical cells of the rhesus monkey in response to precisely controlled stimuli described in our previous publication. Using the All-Interval analytical paradigm we demonstrate: (1) that precisely replicating patterns are present in numbers that cannot be generated through continuous, smoothly varying probability distributions of interspike intervals; (2) that the records contain very large numbers of precisely replicating patterns--doublets, triplets, quadruplets, quintuplets and hextuplets of pulses; (3) that triplet-antitriplet pairs and symmetrical quadruplets are also present in improbable numbers; (4) that different stimuli generate different triplets; (5) and that the first order decay constant of capacity to generate specific precise patterns is a direct function of the number of events making up the patterns and thus that a temporary memory of the occurrence of a pattern exists following the presentation of a stimulus. It is concluded that such patterns of pulses are almost certainly coded symbols related to visual information; that such symbols are sufficiently precise in their replication to permit them to be decoded through spatial summation mechanisms and finally that the ability to generate and the capacity to store such symbols are probably present in the brain as related and coordinated complexes of specific facilitated synapses. Some properties of a proposed model for the production and decoding of such patterns are presented and discussed as are specific mechanisms through which neural networks may implement such functions. Finally, existing and further experimental tests of the mechanisms proposed are outlined.

Animals↗
PubMed1991

Favored patterns in spontaneous spike trains.

By using the modified detection method, favored patterns can be detected in a total of 44 spontaneous spike trains. Among these the 'periodical burst' discharge of one sympathetic preganglionic neuron and the 'fast-slow' alternative discharge of some hypothalamic neurons have visible characteristics, hence we use them to test the reliability of our method by comparing the detected patterns with the non-sequential interval histograms and oscillograms of the spike trains. The comparisons show that our method is reliable. The spike trains of nucleus raphe magnus (NRM) and the locus coeruleus (LC) have no visible characteristics; from these the following results have been observed: (1) all spike trains have one or more favored patterns; (2) some spike trains from neurons in the same nucleus have common fragments of favored patterns; (3) the favored patterns in spike trains recorded from different nuclei are different from each other; (4) some favored patterns in spike trains of the NRM neurons remain unchanged from beginning to end in 35-min records and their repetitions are relatively stable; and (5) microinjection of normal saline or normal serum into the LC has no significant influence on the occurrence of favored patterns in 35-min records of spike trains of the LC neurons. The above results indicate that the favored patterns in spike trains are objective and regular phenomena with relative stability. It seems likely that favored pattern may be used (as an index of the neuronal activity) in combination with the microinjection technique, etc., for various studies including studies on neural coding.

Action Potentials↗
PubMed1992

Modification of medullary respiratory-related discharge patterns by behaviors and states of arousal.

The modulatory influences of behaviors and states of arousal on bulbar respiratory-related unit (RRU) discharge patterns were studied in an unanesthetized, freely behaving guinea pig respiratory model system. When fully instrumented, this model system permits concurrent monitoring and recording of (i) single units from either Bötzinger complex or nucleus para-ambiguus; (ii) electrocorticogram; and, (iii) diaphragmatic EMG. In addition to being used in surveys of RRU discharge patterns in freely behaving states, the model system also offered a unique opportunity in investigating the effects of pentobarbital on RRU discharge patterns before, throughout the course of, and during recovery from anesthesia. In anesthetized preparations, a particular RRU discharge pattern (such as tonic, incrementing or decrementing) typically displayed little, if any notable variation. The most striking development following pentobarbital was a state of progressive bradypnea attributable to a significantly augmented RRU cycle duration, burst duration and an increase in the RRU spike frequencies during anesthesia. In freely behaving states, medullary RRU activities rarely adhered to a fixed, immutable discharge pattern. More specifically, the temporal organization (such as burst duration, cycle duration, and the extent of modulation of within-burst spike frequencies) of RRU discharge patterns regularly showed complex and striking variations, not only with states of arousal (sleep/wakefulness, anesthesia) but also with discrete alterations in electrocorticogram (ECoG) activities and a multitude of on-going behavioral repertoires such as volitional movement, postural modification, phonation, mastication, deglutition, sniffing/exploratory behavior, alerting/startle reflexes. Only during sleep, and on occasions when the animal assumed a motionless, resting posture, could burst patterns of relatively invariable periodicity and uniform temporal attributes be observed. RRU activities during sniffing reflex is worthy of further note in that, based on power spectrum analyses of concurrently recorded ECoG activities, this particular discharge pattern was clearly associated with the activation of a 6-10 Hz theta rhythm. These findings indicated that bulbar RRU activity patterns are subject to change by not only behaviors and sleep/wakefulness cycles, but also a variety of modulatory influences and feedback/feedforward biases from other central and peripheral physiological control mechanisms.

Animals↗
PubMed1992

Fractal geometry of mosaic pattern demonstrates liver regeneration is a self-similar process.

Partial hepatectomy causes compensatory, nonneoplastic growth and regeneration in mammalian liver. Compensatory liver growth can be used to examine aspects of patterns of cell division in regenerating tissue. Chimeric animals provide markers of cell lineage which are independent of growth and can be used to follow cell division patterns. Previous experimental evidence suggests that compensatory liver growth is uniform, without focal centers of proliferation. In this study we have extended that observation to include genes important in regeneration and cell cycle control in order to establish that nascent growth centers are not present in regenerating liver. There is a uniform spatial distribution of expression of these genes which is not related to mosaic pattern in the chimeras. While these genes may help regulate hepatocyte proliferation they do not appear to regulate patch pattern in the chimeras. With this information confirming uniform growth it was possible to use fractal analysis to test various hypothesized patterns of regenerative growth in the liver. The results of this analysis indicate that mosaic pattern does not change substantially during the regenerative process. Patch area and perimeter (the area occupied by or perimeter around cells of like lineage) increase during compensatory liver growth in chimeric rats without alteration of the geometric complexity of patch boundaries (boundaries around cells of like lineage). These tissue findings are consistent with previously reported computer models of growth in which repetitive application of simple decisions assuming uniform growth created complex mosaic patterns. They support the notion that an iterating (repeating), self-similar (a pattern in which parts are representative of, but not identical to the whole) cell division program is sufficient for the regeneration of liver tissue following partial hepatectomy. Iterating, self-similar cell division programs are important because they suggest a way in which complex patterns (or morphogenesis) can be efficiently created from a small amount of stored information.

Animals↗
PubMed1994

Patterns of nuclear immunofluorescence and reactivities to recombinant nuclear antigens in autoimmune hepatitis.

BACKGROUND/AIMS: Antibodies to nuclear antigens have not been fully characterized in autoimmune hepatitis. The aims of this study were to determine the different patterns of immunofluorescence associated with antinuclear antibodies and to correlate these patterns with reactivities to recombinant nuclear antigens and clinical manifestations of autoimmune hepatitis. METHODS: Sera from 65 patients were tested by indirect immunofluorescence and by enzyme immunoassay for antibodies to recombinant centromere, ribonucleoproteins, and ribonucleoprotein complexes. RESULTS: Homogeneous and speckled patterns of immunofluorescence occurred with similar frequencies (34% vs. 38%) in the majority of patients (72%). Patients with speckled patterns were younger and had higher serum aspartate aminotransferase levels at presentation than counterparts with other patterns. Antibodies to centromere (42%) and 52K ribonucleoprotein complex (23%) were the most common reactivities. Of the 35 patients with antibodies, 16 (46%) had multiple specificities. Individual reactivities were not associated with specific immunofluorescent patterns, and they did not identify patients with distinctive features. CONCLUSIONS: Antinuclear antibodies produce mainly homogeneous and speckled patterns of immunofluorescence in patients with autoimmune hepatitis. Speckled patterns are associated with a younger age and greater aminotransferase activity. Multiple autoantibodies are frequently associated with each immunofluorescent pattern. Antibodies to centromere and the 52K ribonucleoprotein complex have a previously unrecognized high frequency and uncertain significance.

Adult↗
PubMed1995

Autoantibodies against malondialdehyde-modified LDL are elevated in subjects with an LDL subclass pattern B.

Small low density lipoproteins (LDL) are more susceptible to in vitro oxidation than larger LDL. To study whether this leads to more oxidation of small LDL in vivo, we determined the level of autoantibodies against malondialdehyde-modified LDL (MDA-LDL) in subjects with small or large LDL (LDL subclass pattern B or A) by ELISA. The study group consisted of 92 subjects with coronary heart disease without severe hypercholesterolemia (mean total plasma cholesterol 5.9 +/- 0.8 mM), 46 with an LDL subclass pattern A and 46 with an LDL subclass pattern B. In the subjects with LDL subclass pattern B the titre of autoantibodies of the IgM class against MDA-LDL was 29% higher than in the subjects with LDL subclass pattern A (P < 0.0001). The concentration of the anti-MDA-LDL autoantibodies of the IgM class was 58% higher in the patients with the pattern B than in the patients with the pattern A (P < 0.0001). There was no statistically significant difference in the titre or concentration of autoantibodies of the IgG class between subjects with LDL subclass patterns A and B. Besides plasma triglyceride and HDL cholesterol, the titre and concentration of the IgM autoantibodies were found to be independent predictors of the LDL subclass pattern. These results show that small LDL are associated with higher autoantibody levels than large LDL. Based on the assumption that the level of autoantibodies against MDA-LDL represents the rate of LDL oxidation in vivo, we conclude that in vivo small LDL is more readily oxidised than larger LDL.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗
PubMed1992

Enhancer trap integrations in mouse embryonic stem cells give rise to staining patterns in chimaeric embryos with a high frequency and detect endogenous genes.

We have generated mouse embryonic stem cell lines that carry lacZ enhancer trap constructs integrated in their genome. Fifty-nine cell lines were analysed for lacZ expression in undifferentiated stem cells and at day 7.5, 8.5 and 12.5 of development in chimaeric embryos obtained after blastocyst injection. In 13 cell lines the lacZ reporter gene was expressed in undifferentiated stem cells ('blue', lines) as monitored by beta-galactosidase activity; 46 cell lines did not show detectable beta-galactosidase activity ('white', lines). In chimaeric embryos one-third of the analysed 59 embryonic stem cell lines gave rise to a variety of patterns. Six out of the 13 'blue' lines and 14 out of the 46 'white' lines showed spatially and temporally regulated patterns of beta-galactosidase expression and were additionally analysed on day 9.5. The majority of patterns showed staining exclusively or predominantly in structures of the developing nervous system, three patterns were observed only or predominantly in non-neuronal structures and five patterns were found exclusively in extraembryonic tissues. The analysis of DNA from cell lines that gave rise to staining patterns in chimaeric embryos showed that in 11 out of 15 cases simple integrations had occurred at a single site while in the remaining four cell lines multiple copies had integrated either at a single or at multiple sites. Flanking sequences from five reporter gene integrations have been cloned. At present, three integration sites have been analysed further and in all three cases we have identified transcribed sequences in the flanking DNA and isolated corresponding cDNA clones. The expression patterns of two of these genes were analysed by RNA in situ hybridisation. In both cases, expression of the endogenous genes was more widespread than the corresponding beta-galactosidase staining, suggesting that the reporter gene responded to only a subset of the regulatory elements of the endogenous gene. Our results demonstrate that enhancer trap integrations in embryonic stem cells can be used to efficiently identify transcriptional activation patterns during mouse embryogenesis and to isolate endogenous genes expressed in spatially and temporally regulated patterns.

Animals↗
PubMed2006

Relationship between patterns of visual field loss and retinal nerve fiber layer thickness measurements.

PURPOSE: To investigate the association between patterns of visual field (VF) loss and retinal nerve fiber layer (RNFL) thickness measurements. DESIGN: Observational cross-sectional study. METHODS: One hundred twenty-one glaucoma patients and 65 healthy subjects from the Diagnostic Innovations in Glaucoma Study (DIGS) were included. All glaucoma patients had repeatable abnormal VFs and scanning laser polarimetry (SLP) RNFL thickness measurements. RNFL measurements were obtained from 16 equal parapapillary sectors. Patterns of VF loss were classified as arcuate, partial arcuate, nasal step, or paracentral in each VF hemifield. Logistic regression analysis was performed to determine which RNFL sectors were associated with each VF pattern. The ability of SLP to discriminate between eyes with different VF patterns and healthy eyes using receiver operating characteristic (ROC) curve analyses also was investigated. RESULTS: VF patterns in the superior hemifield were significantly associated with RNFL sectors in the temporal inferior hemiretina (P < .05). ROC curve areas for discrimination between eyes with different VF patterns and healthy eyes ranged from 0.85 to 0.95. VF patterns in the inferior hemifield were most strongly associated with temporal superior RNFL sectors (P < .05). ROC curve areas for discrimination between different VF patterns and healthy eyes ranged from 0.73 to 0.98. SLP could discriminate between apparently unaffected VF hemifields in glaucoma eyes and VF hemifields in healthy eyes. CONCLUSIONS: Parapapillary RNFL thickness was topographically related to patterns of VF loss. SLP can differentiate between apparently unaffected VF hemifields in glaucoma eyes and normal VF hemifields in healthy eyes.

Aged↗
PubMed2004

Identification of proximal left anterior descending artery stenosis with thallium-201 defect patterns in patients with angina pectoris.

We determined the accuracy of perfusion defect patterns in predicting the presence of proximal left anterior descending (LAD) artery stenosis in patients with angina pectoris. The development population consisted of 80 patients with single-vessel LAD stenosis and reversible LAD territory defects on thallium-201 tomography. The types of defect patterns associated with angiographic proximal LAD stenosis in this population were categorized as "proximal LAD patterns." The accuracy of these patterns for identifying proximal LAD stenosis was evaluated in a separate validation population of 152 patients with angina pectoris. The development population demonstrated LAD territory defects of type I (most of the LAD territory; n = 12); type II (apex, apicoanterior, and most of the septum; n = 26), type III (septum; n = 19); type IV (anteroseptum; n = 6); type V (apex; n = 10); and type VI patterns (anterolateral wall; n = 7). Patients with type I, II, and IV patterns were highly associated with proximal LAD stenosis (38 of 44 segments), whereas those with type III, V, and VI patterns were mostly related to distal LAD disease (29 of 36 segments). In the validation population, proximal LAD patterns had a sensitivity, specificity, and accuracy of 72%, 95%, and 91%, respectively, for identifying patients with proximal LAD stenosis. Test sensitivity was 86% when patients without LAD territory defects were excluded from analysis. Results were virtually identical in the subgroup of 84 patients with stable angina. Thus, recognition of LAD territory thallium defect patterns is useful for identifying patients with angina who are likely to have proximal LAD stenosis.

Aged↗