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Patterns of DNA methylation in selected human genes in different Hodgkin's lymphoma and leukemia cell lines and in normal human lymphocytes.

The human genome, like many other genomes, harbors highly specific patterns of DNA methylation which have not yet been systematically studied. In a limited investigation on the genes for tumor necrosis factors-alpha and -beta, a surprising interindividual concordance in the patterns of DNA methylation at the nucleotide level has been demonstrated earlier by using the genomic sequencing method on DNA from individuals of very different ethnic origins. Patterns of DNA methylation could perhaps serve as indicators for genetic activities. These activities would not have to be restricted to gene transcription but could relate to other genetic activities in the cell. DNA methylation patterns are known to be cell type-specific. We have now initiated a study of these DNA patterns in human lymphocytes and in human cell lines of different malignant origins. Several of the proto-oncogenes, parts of the genes for tumor necrosis factor-alpha and -beta, the insulin receptor and lamin C have been used as hybridization probes. We have relied to some extent on the documented observation that the methylation patterns at 5'-CCGG-3' (HpaII/MspI) sequences yield a reflection of patterns at all 5'-CG-3' sequences. Three main types of patterns have been observed. Some of the probed segments are completely unmethylated; others are fully methylated, most of the areas are partly methylated exhibiting complex patterns at the 5'-CCGG-3' sites. In different tumor cell lines, different DNA methylation patterns are apparent for the same DNA probes. Comparisons of the methylation patterns in a given DNA segment between DNA from primary normal human lymphocytes and DNA from different tumor cell lines reveal changes in these patterns in several instances.

Base Sequence↗

Representation of objective similarity among three-dimensional shapes in the monkey.

Humans have been recently shown to represent parameterized three-dimensional objects in a manner that preserves relative similarities (as measured by parameter-space distances) among the objects (Cutzu and Edelman 1996). We show that the representation of objects in the monkey visual system is similarly faithful to the parametric variation built into the stimulus set. A monkey (Macaca fuscata) performed a delayed matching-to-sample task with 28 images (4 views x 7 objects). Stimuli in each of the two experiments were seven computer-rendered parameterized animal-like shapes, arranged in a low-dimensional configuration (namely, a two-dimensional TRIANGLE) in a common 56-dimensional parameter space. The monkey's task was to match objects (not views). Each experiment lasted for 3-4 weeks after the introduction of the stimulus set to the subject. Error rates were entered into a 7 x 7 object confusion matrix and submitted to nonmetric multidimensional scaling (MDS). In both experiment 1 (mean correct rate 69.7%) and experiment 2 (mean correct rate 59.9%), the MDS solutions resembled closely the low-dimensional parameter-space patterns built into the stimuli, in the sense that the point corresponding to the central one in the original pattern was inside the other six points and that the order of the six points in angular positions around the center point was preserved. A simulation study showed that the resemblance could not be due to chance. These results demonstrate the possibility of veridical representation of parametric similarity among complex objects in the monkey.

Animals↗

Detection of suspected malignant patterns in three-dimensional magnetic resonance breast images.

In this article, a Boolean Neural Network (BNN) is used for the detection of suspected malignant regions in 3D breast magnetic resonance (MR) images. The BNN is characterized by fast learning and classification, guaranteed convergence, and simple, integer weight calculations. The BNN learning algorithm is incremental, which allows the addition and deletion of training patterns without unlearning those already learned. The incremental learning algorithm automatically reduces the training set and trains the network only with those examples estimated to be useful. The architecture is suitable for parallel hardware implementation using available Very Large Scale Integration (VLSI) technology. The BNN was trained by using a set of malignant, benign, and false-positive patterns, extracted by experts, from selected MR studies, by using an incremental learning algorithm. After training, the network was tested by means of a consistency checking test, cross validation techniques, and patterns from actual MR breast images. During the consistency test, the BNN was tested by using the same patterns used for training. The BNN classification accuracy in this case was 99.75%, proving the ability of the BNN to select useful patterns from the training set. Then, a leave one out cross-validation (LOOCV) test was done by using patterns from the training set and the classification accuracy was 90%. Next, an extended training set was created by shifting the original patterns in different directions. A cross-validation test was then performed by dividing the set of patterns into a training and a test set. Classification accuracy was compared to the nearest neighbor classifier. Results showed that the BNN achieved an average of 77% classification accuracy while requiring only 34% of the original training set. On the other hand, the nearest neighbor classifier achieved an accuracy of 57.9% while retaining the whole training set. Another test using actual MR slices different from the training set was done and results compared favorably to a radiologist's findings. Test results show the BNN's capability to detect suspected malignant regions in 3D MR images of the breast. The proposed BNN architecture can save the radiologist a great deal of time browsing MR slices searching for suspected malignancies.

Algorithms↗

Chronic addiction relapse treatment: a study of the effectiveness of the high-risk identification and prediction treatment model. Part II. The HRIPTM case table, case study examples and questionnaire.

The high-risk identification and prediction treatment model (HRIPTM) was developed to investigate the physiological and psychological conditions associated with the concept of negative emotional state, and to examine the origin and evolution of this condition in relation to addiction relapse. An in depth case study sample of n=30 was conducted within the context of an intensive outpatient addiction treatment program based on the HRIPTM. The HRIPTM investigates the nature of problematic repetitive behavior patterns originating in the childhood developmental period, the individual nature of negative emotional state in relation to these patterns and their evolution, and their influence on addiction vulnerability and addiction relapse. The preliminary study upon which this model was based emphasized the importance of developing methods for accumulating information that pinpoints lifespan experiences associated with the origin of problematic behaviors, the level of emotional intensity factors associated with behavior pattern construction and development, and level of associated risk potential as it manifests in each individual case. Recent neuroscientific studies into the early developmental process are producing increased evidence of the enormous influence of this period on later developmental processes. Addiction, in itself a developmental process, may be more influenced by pre-addiction factors than previously assumed. This model addresses those influences. The study was conducted to determine whether or not information that arises from the HRIPTM increases the patient's and clinician's ability to address addiction relapse more effectively. As a result of completion of the HRIPTM program, the sample n=30 reported gained ability to address recovery processes more effectively. The 12-question HRIPTM Questionnaire instrument, when tabulated, revealed that of the 360 total responses, less than 2% disagreed that ability had been gained in all suggested areas defined in the questionnaire. Over 98% agreed or strongly agreed that ability had been gained in the defined areas.

Adult↗

Chronic addiction relapse treatment: a study of the effectiveness of the high-risk identification and prediction treatment model. Part III. Conclusion and future implications of HRIPTM research.

The high-risk identification and prediction treatment model (HRIPTM) was developed to investigate physiological and psychological conditions associated with the concept of negative emotional state, and to examine the origin and evolution of this condition in relation to addiction relapse. An in depth case study sample of N=30 was conducted within the context of an intensive outpatient addiction treatment program based on the HRIPTM. The HRIPTM investigates the nature of problematic repetitive behavior patterns originating in the childhood developmental period, the individual nature of negative emotional state in relation to these patterns and their evolution, and their influence on addiction vulnerability and addiction relapse. The preliminary study on which this model was based emphasized the importance of developing methods for accumulating information that pinpoints life span experiences associated with the origin of problematic behaviors, the level of emotional intensity factors associated with behavior pattern construction and development, and the level of associated risk potential as it manifests in each individual case. Recent neuroscientific studies into the early developmental process are producing increased evidence of the enormous influence of this period on later developmental processes. Addiction, in itself a developmental process, may be more influenced by pre-addiction factors than previously assumed. This model addresses those influences. The study was conducted to determine whether information that arises from the HRIPTM increases the patient's and clinician's ability to address addiction relapse more effectively. Because of the completion of the HRIPTM program, the sample n=30 reported gained ability to address recovery processes more effectively. The 12-question HRIPTM Questionnaire instrument, when tabulated, revealed that of the 360 total responses, less than 2% disagreed that ability had been gained in all suggested areas defined in the questionnaire. Over 98% agreed or strongly agreed that ability had been gained in the defined areas.

Humans↗

Development of the rat thalamus: IV. The intermediate lobule of the thalamic neuroepithelium, and the time and site of origin and settling pattern of neurons of the ventral nuclear complex.

Short-survival, sequential, and long-survival thymidine radiograms of rat embryos, fetuses, and young pups were analyzed in order to examine the time of origin, settling pattern, migratory route, and site of origin of neurons of the ventral nuclear complex of the thalamus. Quantitative examination of long-survival radiograms established that the bulk of the neurons of the ventral nuclear complex are generated between days E14 and E16 but with statistically significant differences between its three nuclei. The ventrobasal nucleus is the oldest component (97% of the cells are generated on days E14 and E15); the ventrolateral nucleus is next (82% of the cells are generated on days E14 and E15); and the ventromedial nucleus is last (51% of the cells are generated on days E14 and E15). In addition to this caudal-to-rostral (from the ventrobasal nucleus to the ventrolateral nucleus) and lateral-to-medial (from the ventrobasal nucleus to the ventromedial nucleus) internuclear gradients, there are lateral-to-medial and ventral-to-dorsal intranuclear neurogenetic gradients within the ventrobasal and ventrolateral nuclei. Qualitative examination of short and sequential survival thymidine radiograms indicate that the neurons of the ventral nuclear complex originate in the unique intermediate thalamic neuroepithelial lobule, which is distinguished from the rest of the thalamic neuroepithelium by the presence of a mitotically active secondary neuroepithelial matrix. Two sublobules can be distinguished in the intermediate lobule during the early stages of thalamic development. On the basis of their location and chronological pattern of cell production and differentiation, it is inferred that the neurons of the ventrobasal nucleus originate in the earlier differentiating, posteroventrally situated inverted sublobule, and the neurons of the ventrolateral nucleus are produced in the later differentiating, anterodorsally situated everted sublobule. The neurons of the ventromedial nucleus appear to originate from the intermediate neuroepithelial lobule after its two sublobules are no longer distinguishable. The heavily labeled neurons generated soon after injection on day E15 form a wave front that translocates in a lateral direction at a steady rate of 215 microns/day. Examination of methacrylate-embedded materials showed that, in day E15 rats the actively migrating cells are spindle-shaped, with their long axis oriented horizontally. The far-laterally situated differentiating cells (the oldest neurons) become vertically oriented by day E16. Associated with this change in polarity, vertically oriented fibers appear among the cells. These fibers can be traced to the inte

Animals↗

Chronic addiction relapse treatment: a study of the effectiveness of the high-risk identification and prediction treatment model. Part I.

The high-risk identification and prediction treatment model (HRIPTM) was developed to investigate physiological and psychological conditions associated with the concept of negative emotional state, and to examine the origin and evolution of this condition in relation to addiction relapse. An in-depth case study sample of n=30 was conducted within the context of an intensive out-patient addiction treatment program based on the HRIPTM. The HRIPTM investigates the nature of problematic repetitive behavior patterns originating in the childhood developmental period, the individual nature of negative emotional state in relation to these patterns and their evolution, and their influence on addiction vulnerability and addiction relapse. The preliminary study, upon which this model was based, emphasized the importance of developing methods for accumulating information that pinpoints lifespan experiences associated with the origin of problematic behaviors, the level of emotional intensity factors associated with behavior pattern construction and development, and level of associated risk potential as it manifests in each individual case. Recent neuroscientific studies into the early developmental process are producing increased evidence of the enormous influence of this period on later developmental processes. Addiction, in itself a developmental process, may be more influenced by pre-addiction factors than previously assumed. This model addresses those influences. The study was conducted to determine whether or not information that arises from the HRIPTM increases the patient's and clinician's ability to address addiction relapse more effectively. As a result of completion of the HRIPTM program, the sample n=30 reported gained ability to address recovery processes more effectively. The 12-question HRIPTM Questionnaire instrument, when tabulated, revealed that of the 360 total responses, less than 2% disagreed that ability had been gained in all suggested areas defined in the questionnaire. Over 98% agreed or strongly agreed that ability had been gained in the defined areas.

Humans↗

Restoration of motor unit properties and fiber type distribution in reinnervated axolotl skeletal muscle.

The contractile properties of functionally isolated motor units and the muscle fiber type distribution of reinnervated iliotibialis posterior muscles were examined in axolotls (Ambystoma mexicanum) 7 to 12 months after complete transection of the hind limb nerve trunks. Motor units were continuously distributed with respect to size and contractile speeds and there was a positive correlation between motor unit size and twitch:tetanus ratio. The degree of overlap between motor units was positively correlated with motor unit size and inversely correlated with similarity of contractile speeds. In addition, the muscle fiber type distribution within the reinnervated muscles, as revealed by immunocytochemical localization of tonic, slow, and fast myosin isoforms, was indistinguishable from that in the contralateral unoperated muscles, with no evidence of fiber type grouping. Thus, the motor organization after reinnervation was very similar to that of normal muscles examined previously. The only difference found was that a small number of motor units contracted unusually rapidly in reinnervated muscles. The absence of muscle fiber type redistribution and the essentially normal motor unit characteristics suggest that the original pattern of synaptic connections was reestablished following reinnervation. These observations are consistent with the returning motor neurons selectively reinnervating their original muscle fiber types.

Ambystoma mexicanum↗

Development of the rat thalamus: II. Time and site of origin and settling pattern of neurons derived from the anterior lobule of the thalamic neuroepithelium.

Short-survival, sequential, and long-survival thymidine radiograms of rat embryos, fetuses, and young pups were analyzed in order to examine the time of origin, settling pattern, and neuroepithelial site of origin of the anterior thalamic nuclei--the lateral dorsal (lateral anterior), anterodorsal, anteroventral and anteromedial nuclei--and of two rostral midline structures--the anterior paraventricular and paratenial nuclei. The neurons of the lateral dorsal nucleus are generated over a 3-day period between days E14-E16 and their settling pattern displays a combined lateral-to-medial and dorsal-to-ventral neurogenetic gradient. The bulk of the neurons of the anteroventral nucleus are generated over a 3-day period between days E15-E17 and settle with an oblique lateral-to-medial and ventral-to-dorsal neurogenetic gradient. The bulk of the neurons of the anteromedial nucleus are generated over a 2-day period between days E16-E17 and show the same settling pattern as the anteroventral nucleus. The neurons of the anterodorsal nucleus are generated over a 3-day period between days E15-E17 and show a lateral-to-medial neurogenetic gradient. The bulk of the neurons of the central part and lateral part of the paraventricular nucleus are generated over a 2-day period (E16-E17 and E17-E18, respectively) and each part displays a ventral-to-dorsal neurogenetic gradient. Finally, the bulk of the neurons of the paratenial nucleus are generated over a 4-day period between days E15-E18 and settle with a lateral-to-medial neurogenetic gradient. Observations are presented that the anterior thalamic nuclei, constituting the distinct "limbic thalamus," derive from a discrete neuroepithelial source. This is the crescent-shaped germinal matrix lining the diencephalic (medial) wall of the hitherto unrecognized anterior transitional promontory, which we call the anterior thalamic neuroepithelial lobule. On day E16 three migratory streams leave the anterior neuroepithelial lobule and, on the basis of their labeling pattern in relation to the neurogenetic gradients of the anterior thalamic nuclei, they are identified, from dorsal to ventral, as the putative migratory streams of the anterodorsal, anteroventral, and lateral dorsal nuclei. On day E17 the putative migratory stream of the anteromedial nucleus appears to leave the same neuroepithelial region that on the previous days was the source of the anteroventral nucleus. Dorsally, two neuroepithelial patches persist after day E17 and these are identified as the putative cell lines of the anterior paraventricular and paratenial nuclei.

Animals↗

Amphetamine stereotypy: the influence of environmental factors and prepotent behavioral patterns on its topography and development.

This report describes a series of experiments, all of which demonstrate a strong contribution of the behavioral pattern manifested at the time of initial amphetamine injection to the topography and development of the stereotypy that develops with chronic amphetamine intoxication. These initial behavioral patterns reflect (i) learned behaviors, (ii) species-specific behaviors, (iii) behaviors associated with amphetamine arousal, and (iv) novel behaviors reflecting unique environmental circumstances prevailing at the time of administration. In an experiment using eight dogs administered amphetamine in a situation which allowed interaction between the animals, the behavioral stereotypies that developed were comprised of the social interaction patterns ongoing at the time of initial drug effects. Experiments with rats have demonstrated that the configuration of the enclosure in which they are injected influences the initial behavioral reactions to amphetamine and thus modifies the stereotypy. In experiments with cats pressing a lever to self-administer amphetamine, investigatory behavior at the lever-press operandi becomes incorporated as does the learned behavior response into the stereotypy. The behavioral patterns originally associated with amphetamine arousal eventually supersede the learned response component of the stereotypy. Finally, monkeys incorporate components of the initial behaviors associated with amphetamine administration into a wider range of stereotype patterns over months of chronic intoxication, and eventually the stereotypy may evolve into a specific dyskinesia involving movements of the original behavioral component.

Animals↗

Flow cytometric study on cell kinetics of brain tumours and their cultured cells.

With the aid of flow cytometry (FCM), distribution of DNA content in 40 cases of brain tumour, primary culture cell, and secondary culture cell can be determined and chronological change after subculture is studied from the analysis of their cell cycle. In most primary cultures, proliferating index (PI) is likely to decrease, which suggests that environmental change might affect the growth activity. In comparison with that of the original sample, DNA-histogram of the secondary culture can be divided into the following 3 types: the type recovering to the original pattern ("adapting type"), in which astrocytoma, ependymoma, glioblastoma and medulloblastoma are included, 2) the type increasing more at G2 + M phase than the original ("proliferating type"), in which meningioma and some of glioblastoma are included, and 3) the type decreasing so far as to induce degeneration or death ("degenerating type"), in which pituitary adenoma and neurinoma are included. FCM is of great usefulness for the study of cell kinetics of a tumour cell undergoing culture and the present method will be available for the respective study of biological characteristics of the cultured cell, established cell line or sensitivity test for antineoplastic agents.

Brain Neoplasms↗

Pseudonodular T cell lymphoblastic lymphoma.

T cell lymphoblastic lymphoma usually presents as a rapidly growing lymphoma with histologic features of a diffuse, poorly-differentiated small cell lymphoma with a high mitotic rate. This report describes a patient who presented with an aggressive small cell lymphoma that morphologically had a nodular pattern. Repeated biopsy and use of cell surface markers resulted in reclassifying the cell type as T cell lymphoblastic and in recognizing the original pattern as pseudonodular. The routine application of these immunologic techniques in patients with lymphoma may lead to more accurate diagnoses and improved treatment.

Adult↗

Development of the rat thalamus: III. Time and site of origin and settling pattern of neurons of the reticular nucleus.

Short-survival, sequential, and long-survival thymidine radiograms of rat embryos, fetuses, and young pups were analyzed in order to examine the time of origin, settling pattern, migratory route, and site of origin of neurons of the reticular nuclear complex of the thalamus. On the basis of its chrono-architectonics, the reticular nucleus was divided into a central, medial, and lateral subnucleus. The central subnucleus is the earliest produced component of the entire thalamus with over 50% of its neurons being generated on day E13 and another 40% on day E14. Peak production of neurons of the lateral and medial subnuclei is on day E14. There is a lateral (earlier) to medial (later) neurogenetic gradient between these two components of the reticular complex: only about 12% of the lateral subnucleus neurons, but close to 30% of the medial subnucleus neurons, are generated on day E15. Because the lateral and medial subnuclei display the typical outside-in gradient found in the thalamus, they are considered to constitute a single cytogenetic sector; the early generated central subnucleus, which violates this order, is considered to constitute a separate cytogenetic sector. Observations are presented that neurons of the central reticular subnucleus originate in a unique neuroepithelial region, the reticular protuberance. The migration of heavily labeled cells was traced from this region in rats labeled with 3H-thymidine on day E13 and killed on the subsequent days. The neurons of the lateral and medial reticular subnuclei originate in the reticular lobule of the thalamic neuroepithelium. The migration of heavily labeled, spindle-shaped cells was traced from this region in rats labeled with 3H-thymidine on days E14 and E15 and killed at daily intervals thereafter. The neurogenetic gradient of the reticular thalamic complex seen in postnatal rats is established before birth.

Animals↗

Castability of a commercial castable glass ceramics.

This study was carried out to determine the design and thickness of the cervical margin of a castable ceramic restoration from the point of view of its castability. Castability of castable ceramics was lower compared to Ag-Pd-Au and Co-Cr alloy with the use of the mesh pattern and rod pattern test (p < 0.05). It was more dependent on the pattern thickness than alloys (p < 0.05), and perfect reproducibility with non-measurable variability could be estimated to reach 1.0 mm thickness of the original pattern (p < 0.001). Marginal shape was certainly more reproducible in a right angle shoulder than in 30, or 45 degree bevels (p < 0.05). From these results, it is suggested that a right angle shoulder margin with 1.0 mm thickness is more suitable to castable glass ceramic restoration than any other design.

Analysis of Variance↗

Evidence for salt-associated restriction pattern modifications in the archaeobacterium Haloferax mediterranei.

DNA restriction pattern modifications were detected when Haloferax mediterranei was grown in low (10%) salt concentrations. After cells were grown again in optimal (25%) salt concentrations, the original pattern was recovered. These salt-associated DNA modifications were revealed with 5% of the 160 DNA fragments cloned and used as probes in hybridization experiments. Patterns obtained when genomic DNA was digested with different restriction enzymes showed that these modifications are related not to insertions or deletions in genome but to modifications of some specific sequences.

Archaea↗

Neuromuscular patterns and the origin of trophic specialization in fishes.

The pattern of muscle electrical activity in the pharyngeal muscles of the mollusc-eating sunfish Lepomis microlophus is highly specialized in comparison with the pattern displayed by most other members of the sunfish family and does not change when different prey are eaten. The closest genealogical relative of this species has the specialized muscle activity pattern for crushing prey when it feeds on snails but uses the primitive sequence of muscle activity during swallowing of other prey. The ability of species that crush snails to use molluscan prey effectively is due primarily to the evolutionary transformation of the neuromuscular program controlling the trophic apparatus.

Action Potentials↗

[Diagnosis of periorbital diseases by means of ultrasound].

The ophthalmology was one of the first medical branches which used ultrasound in diagnostical purposes. The structure of the eye, with the large vitreous body, through which the ultrasound waves pass without attenuation, is highly appreciated in ultrasound examination, thus the diagnostical results of ocular diseases are extremely good. On the base of our rich ophthalmological experience we left the scope of the eye and the orbit, and made ultrasound examinations of the head and the face. The echograms of two patients presented original patterns: one was malignant melanoma of the skin with typical echograms performed by A and B scannings, and the other case was the Mikulicz disease with typical echograms. Original echograms of these patients can be considered as a contribution to ultrasound diagnosis of paraorbital diseases.

Humans↗

[Anatomo-radiological study of the origin of the arteria ascendens, a colic branch of the ileocolic artery].

With the inadequate anatomic revision observed in the literature, the authors tried to establish the most frequent origin patterns of the arteria ascendens, colic branch of the ileocolic artery. The search consisted of one hundred cases and it was possible to distinguish four fundamental types of vascular origin. The absence of studies in radiological anatomy made this contribution very important for the knowledge of the arterial disposition in the modern diagnostic procedures of the region.

Adolescent↗