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The acetochlor registration partnership state ground water monitoring program.

The Acetochlor Registration Partnership (ARP) conducted a 7-yr ground water monitoring program at a total of 175 sites in seven states: Illinois, Indiana, Iowa, Kansas, Minnesota, Nebraska, and Wisconsin. While acetochlor [2-chloro-N-(ethoxymethyl)-N-(2-ethyl-6-methylphenyl)-acetamide] was the primary focus, the analytical methods also quantified alachlor [2-chloro-N-(2,6-diethylphenyl)-N-(methoxymethyl)-acetamide], atrazine [6-chloro-N-ethyl-N'-(1-methylethyl)-1,3,5-triazine-2,4-diamine], metolachlor [2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl)-acetamide], and two classes of soil degradates for acetochlor, alachlor, and metolachlor. Ground water samples were collected monthly for five years and quarterly for two additional years. All samples were analyzed for the presence of parent herbicides, and degradates were monitored during the last three years. Parent acetochlor was detected above 0.1 microg L(-1) in three or more samples at just seven sites. Alachlor and metolachlor were also rarely detected, but atrazine was detected in 36% of all samples analyzed. Even more widespread were the tertiary amide sulfonic acid (ethanesulfonic acid, ESA) degradates of acetochlor, alachlor, and metolachlor, which were detected at 81, 76, and 106 sites, respectively. The other class of monitored soil degradates (oxanilic acid, OXA) was detected less frequently, at 26, 16, and 63 sites for acetochlor OXA, alachlor OXA, and metolachlor OXA, respectively. The geographic distribution of detections did not follow the pattern originally expected when the study began. Rather than being a function primarily of soil texture, the detection of these herbicides in shallow ground water was related to site-specific factors associated with local topography, the occurrence of surface water drainage features, irrigation practices, and the vertical positioning of the well screen.

Agriculture↗

Dynamic QSAR techniques: applications in drug design and toxicology.

The basic principles of 3-D quantitative structure-activity relationships (QSARs) analysis are discussed in the light of the fuzzy logic concept. According to that concept, the traditionally one chemical - one structure - one parameter value relationship in QSAR is suggested to be modified into one chemical finite set of structures - range of parameter values principle. In this respect, two recently developed techniques accounting for conformational flexibility in 3-D QSARs are reviewed. A basic assumption underlying both methods is that chemical behavior in complex biological systems is context-dependent. A molecule can exist and interact in a variety of conformations depending on the specificity of the endpoint under investigation and reaction media. It was demonstrated that selection of active conformer(s) in QSAR studies is a task as important as the selection of relevant molecular parameters. Specifically selected active conformers, rather than the lowest-energy states of the chemicals are suggested to be used in the correlative QSARs. The method for recognition the common reactivity pattern (COREPA) of structurally heterogeneous compounds that elicit similar biological behaviour is based on all energetically reasonable conformers of chemicals. The principle assumption of the method is that biologically similar chemicals should possess a commonality in their stereoelectronic (reactivity) pattern. Originally developed algorithms for conformer generation are presented in association with the QSAR methods accounting for conformational flexibility of chemicals. Applicability of the QSAR technique for selection active conformers is illustrated by presenting QSAR models derived for Ah binding affinity of PCBs and antimicrobial activity of rifamicin derivatives. Models for predicting estrogenic activity of structurally diverse chemicals and ACE inhibition exemplified the applicability of the COREPA method. The model performance is analyzed by the 3D screening exercise of large chemical inventories with subsequent experimental validation within the EDAEP project. Besides the impact of conformational flexibility of chemicals in 3D QSAR the role of different molecular descriptors is discussed with respect to their ability to describe molecular interactions with different specificity.

Combinatorial Chemistry Techniques↗

Responding to perceived needs of the twenty-first century: a case study in curriculum design.

Mercer University School of Medicine was established in response to the shortage of primary care physicians in medically underserved Georgia. Originally patterned after the McMaster model of medical education, Mercer found it necessary to modify the three academic programs of the first 2 years of a 4-year undergraduate medical education curriculum. Since accepting students in 1982, though, it has retained many of the essential qualities of problem-based learning and those educational experiences that prepare community responsive physicians to practice in medically underserved areas.

Curriculum↗

[The cytologic diagnosis of rare lung tumors (author's transl)].

The cytologic diagnosis of typical cell pattern originating in rare lung tumours gets a supplementary value for an accurate diagnostic prediction in addition to histologic examinations. Comparison was made by use of light and electron microscopy between three bronchogenic carcinoid tumours, two melanomas metastasizing to the lung, and one plasmacytoma in the lung. The cytologic diagnosis from dab smears and the electron microscopy are able to give an accurate diagnostic decision examinating some single difficult cases by - demarcating the cells of carcinoid tumours from the oat cells originating in undifferentiated small cell anaplastic carcinomas - differentiating plasma cells using May-Grünwald-Giemsa stained smears - detecting melanin by using electron microscopy in the nonpigmented melanomas metastasizing to the lung.

Carcinoid Tumor↗

[Congenital hereditary motor and sensory neuropathy].

The authors report 6 cases of hereditary sensorimotor neuropathy (HSMN) presenting with the following clinical features: (1) severe outcome (3 out of 6 patients died before the age of 4 years), and (2) intellectual impairment (3 out of 6 cases). Histopathological study of nerve biopsies gave heterogeneous results: there was one case of axonal neuropathy (HSMN II of Dyck and Lambert), one case of demyelinating neuropathy with Schwann's cell proliferation (HSMN III of Dyck and Lambert), and one case of giant axonal neuropathy. The last three cases displayed an original pattern hitherto unknown in classical delayed HSMN, with complete disappearance of myelinated sheaths and Schwann's cell proliferation. This particular pattern did not seem to be due to the biopsy being performed at an early stage, since in one case a second biopsy showed the same histological features.

Female↗

Mouse opsin. Gene structure and molecular basis of multiple transcripts.

The single copy mouse opsin gene produces five major transcripts, varying in size from 1.7 to 5.1 kilobases. The mRNAs are present at levels that vary over 2 orders of magnitude and can be detected as early as postnatal day 1. Each of the transcripts is polyadenylated and can be identified in polysome-bound RNA, suggesting that each is translated in vivo. To elucidate the molecular basis of this complex transcription pattern, we have characterized genomic fragments covering the entire mouse opsin gene, including several kilobases of 5'- and 3'-flanking regions. Transcription initiates at a single site 97 base pairs upstream of the translation start codon. Northern hybridization with exon- and intron-specific probes demonstrated that the various transcripts are not generated by partial or alternative splicing. Sequence analysis of the 3' end of the gene showed the presence of multiple polyadenylation signals. Analysis by polymerase chain reaction of the 3' end of opsin cDNA demonstrated that the complex transcription pattern originated from the selective use of these polyadenylation sites, generating transcripts that differ only in the length of the 3'-untranslated region. Transcript heterogeneity similar to that observed in mouse was also found in rat and, to a lesser degree, in human and frog opsin mRNAs.

Amino Acid Sequence↗

Multiple forms of gamma-glutamyltransferase and lipoproteins.

The gamma-glutamyltransferase isoenzyme patterns originating from human serum and homogenates of liver, kidney, pancreas and intestine in the presence and in absence of isolated lipoproteins has been studied. On the basis of these results one can conclude that the distribution of a variety of gamma-glutamyltransferase activities obtained by the electrophoresis of blood serum is not a consequence of an existence of a large number of true isoenzymes, but of increased concentrations of lipoproteins which bind to the enzyme thus causing the appearance of gamma-glutamyltransferase in the region of the appropriate lipoproteins.

Humans↗

[Associative learning in a neuromimetic network with local competitions].

Presented here is a neuromimetic model for the learning of associations between activity patterns originating from recoding layers. These layers are described as networks of cellular clusters made up of competitive formal neurons. A rule of synaptic plasticity with improved neurobiological realism is proposed; it allows for fast learning of large sets of associations.

Association Learning↗

heterogeneity of creatine kinase isoenzyme MM in serum in myocardial infarction: interconversion of the "normal" and "abnormal" sub-bands by glutathione.

We used isoelectric focusing (IEF) in polyacrylamide gels to investigate the effects of glutathione on the sub-bands of serum creatine kinase (CK; EC 2.7.3.2) isoenzyme MM in acute myocardial infarction. The intensity of the "abnormal" sub-bands c (pI 7.25), e (pI 6.85), and g (pI 6.50) increased, and that of the "normal" sub-bands 1 (pI 6.91), 2 (pI 6.65), and 3 (pI 6.35) decreased, following serum incubation with reduced glutathione (GSH, final concentration 1.25 mmol/L). Further incubation with oxidized glutathione (GSSG, final concentration 5 mmol/L) reversed this change and restored the original pattern, whereas GSSG at 7.5 mmol/L caused sub-bands c, e, and g to disappear and sub-bands 1, 2, and 3 to be enhanced. Sequential incubation of serum with 2.5 mmol of GSSG and 7.5 mmol of GSH per liter produced the opposite sequence of events; i.e., the "abnormal" sub-bands disappeared then reappeared (and GSH at 10 mmol/L enhanced their reappearance). At higher concentrations, glutathione (GSH or GSSG) impaired the detection of the CK-MM sub-bands after IEF, an effect that was "quenched" by heat-inactivated serum of low CK activity. Likewise, the intensity of tissue CK-MM (corresponding to myocardium extracted into 100 mmol/L Tris HCl buffer, pH 7.4) was greatly enhanced by adding heat-inactivated serum to the tissue extract before IEF. We discuss the significance of these findings for the diagnosis of myocardial infarction.

Creatine Kinase↗

Induction and the organization of the body plan in Xenopus development.

Various experiments are surveyed in this paper that may throw light on how the degree of spatial organization of the Xenopus embryo increases during development. The events of the 100 minutes or so that follow fertilization may do little more than orientate and give proportions, within the egg's yolky vegetal region, to the system that originates patterned inductive signals for organization of the mesodermal and ectodermal regions during blastula stages (10(2)-10(4) cells). By onset of gastrulation, an outline plan for mediolateral and anteroposterior body organization has developed within induced tissue around the equator of the embryo, which seems to control subsequent development in two ways. It sets the spatial and temporal pattern of mechanical activities whereby the mesoderm rudiment drives the crucial shape changes that lay it and the neural rudiment out correctly. It is also the probable starting point for positionally specific gene transcription that begins immediately after gastrulation. Experiments with known inducing factors that explore the possible bases for the early 'pre-organization' in mesoderm are informative, but leave us far from a complete understanding. Evidence that inhibitory or modulating, as well as activating, signals are involved is surveyed.

Animals↗

Regeneration of the caudal and pectoral fins of a bony fish, Gambusia (Haplochilus) schoelleri.

The study showed that excision of the caudal fin at basal level was followed by complete regeneration in one and a half months, whereas if it was amputated at mid-fin level, complete regeneration took two months. The findings confirm that the greater the extent of amputation, the faster the rate of regeneration. In the case of the pectoral fin, only part of which was removed, it was found that the fin completely regenerated, with recovery of its original pattern, within two months after amputation.

Animals↗

T cell differentiation stages identified by molecular and immunologic analysis of the T cell receptor complex in childhood lymphoblastic leukemia.

T cell differentiation was investigated by determining the relationship of T cell receptor (Ti) gene rearrangement and transcription to the expression of surface and cytoplasmic T3 antigen using blast cells from five children with acute lymphoblastic leukemia of thymic origin. Patterns of monoclonal antibody (MoAb) reactivity indicated that these cases were representative of the three recognized stages (I, II, III) of human thymocyte development. The T3 antigen, which becomes linked to the Ti to form a functional T cell receptor complex on mature thymocytes, was expressed on the cell surface in two cases (stage III). However, in the remaining three cases that were surface T3 negative (stages I and II), large amounts of T3 were identified in the cytoplasm by immunoperoxidase staining and flow cytometry. Leukemic blasts from all five patients showed rearranged genes encoding the beta-chain portion of the Ti heterodimer. RNA transcripts of Ti beta-chain genes were also evident in lymphoblasts from all five cases, but transcripts coding for the alpha-chain portion of Ti were found only in cases that expressed T3 on the cell surface. Thus the absence of surface T3 (and presumably Ti) coincides with the absence of Ti alpha-chain RNA, suggesting that transcription of alpha-chain genes is a critical regulatory event in the surface expression of the Ti-T3 complex. Leukemic T cells that rearrange and express Ti beta-chain genes but lack Ti alpha-chain messenger RNA (mRNA) may represent a stage of differentiation analogous to pre-B cells, where heavy-chain immunoglobulin (Ig) genes are rearranged and expressed but light-chain Ig genes are not expressed.

Antibodies, Monoclonal↗

Biochemical mediators involved in the inflammatory reaction. Protective activity of S 5682.

Increased vascular permeability of inflammation is accounted for by the formation/release of mediators, such as lipids derived from arachidonate (eicosanoids: prostaglandins, thromboxane A2 or leukotrienes) or from ether phospholipids (PAF-acether). Acute inflammation can be controlled by inhibitors of mediator synthesis or by antagonists, as well as at the level of the reactivity of vascular endothelium or leukocytes. This modulation can be obtained with flavonoids, such as S 5682, a precise fraction of diosmin and hesperidin, which reduces the vascular permeability of the rabbit skin and increases the resistance of rat microvessels. After chronic treatment by the oral route with S 5682, the synthesis of PGE2, PGF2 and TxB2 decreased in inflammatory granuloma in the rat, induced by introducing subcutaneously polyurethane pellets. We carried out studies to see if S 5682 modifies the amounts of TxB2, of PGE2 and of PGI2 formed by perfused guinea-pig lungs injected with PAF-acether (1-100 ng). At 5-50 microM, S 5682 favoured the formation of PGE2 and of prostacyclin, and less that of thromboxane. At higher concentrations, the stimulation of the formation of eicosanoids was less marked, suggesting a biphasic effect. The biosynthetic profile of eicosanoids was affected at low concentrations the flavonoids with a complex and original pattern.

Acute-Phase Reaction↗

Identification of a differentiation-specific cell surface antigen on HL60 cells that is associated with proliferation.

We have produced a murine IgM monoclonal antibody (Y201) that recognizes a cell surface antigen present on HL60 cells. Seventy percent of uninduced HL60 cells expressed Y201 antigen, while the remainder did not. There were no morphological differences between HL60 cells that expressed Y201 antigen and cells that did not express Y201 antigen. Cells with the greatest number of antigenic sites were found to have greater proliferative capacity in liquid culture and in soft agar than did HL60 cells deficient in this marker. Expression or lack of expression of the Y201 antigen is not constant over a prolonged period in that both subpopulations ultimately reproduced the original pattern of antigenic expression when grown in liquid culture. The antigen identified by Y201 was lost with terminal differentiation of HL60 cells using a variety of inducers. Loss of Y201 antigen during differentiation was associated with a decrease in proliferative capacity in soft agar. Loss of Y201 antigen by greater than 95% of differentiated HL60 cells was associated with loss of proliferative capacity. These data suggest that HL60 cells are heterogeneous in regard to proliferative capacity and that this heterogeneity is associated with expression of the cell surface antigen identified by Y201.

Antibodies, Monoclonal↗

[Adaptation of food ingestion to energy expenditure].

Body energy balance is regulated in adults. The accuracy of the phenomenon is particularly evident in laboratory animals under steady conditions. Moreover, it has been repeatedly demonstrated that this balance is maintained in spite of fluctuations in food intake or energy expenditure. When animals such as rats, dogs or rabbits are presented with a diluted or concentrated version of familiar food, they compensate rapidly by increasing or decreasing their ponderal intake. This is achieved first by a change in meal frequency, then meal size adapts to the new caloric content and meal frequency returns to the original pattern. This adaptation is based on the learning of post-ingestive cues. Hypo or hyperphagia leads to reduced or increased energy expenditure, as the case may be; the basal metabolic rate is modulated by thyroid hormones and diet-induced thermogenesis by the sympathetic system. These variations are partly regulatory. In a cold environment, the increase in energy expenditure caused by increased thermogenesis is rapidly compensated by increased caloric intake. Physical activity activates the sympathetic system responsible for numerous hormonal changes, the most important of which is insulin hyposecretion. In animals or humans, moderate aerobic exercise induces a small weight loss; afterwards, weight gain is normalized and increased caloric intake compensates for energy expenditures such as exercise, increased basal metabolic rate and diet-induced thermogenesis. Extreme changes in body weight and fat are produced by gestation and lactation; they are satisfactorily explained by concomitant hormonal changes. Especially during lactation, food intake is regulated so that it allows body weight to return to pregestation level. Studies on the mechanisms implicated in the regulation of body energy balance are still in progress. Friedman and Ramirez (1985) suggest that the way fatty acids are utilized is important. Kasser et al. (1985) show a striking difference in the cellular metabolism of hypothalamic regions, depending on the metabolic state or the animal, and Woods et al. (1985) strongly suggest a role for the central insulin level. These hypotheses are well-documented and not exclusive of each other.

Adaptation, Physiological↗

[Local rotational flap of the nail].

An original pattern of nail flap is described. It consists of a longitudinal band of lateral nail matrix and bed associated with its lateral wall. A vascular anatomic study with latex neopren infusion has been performed. The dorsal branch of the medial phalangeal artery could be shown to be the arterial pedicle of the flap. The venous system was shown to be concomitant. Eight nail autoplasties have been performed in eight cases, proving the reliability of the flap. It provides an interesting way of reconstruction of the nail in tumors, black longitudinal nail bands, posttraumatic and also post-infectious lesions of the nail.

Adult↗

Scanning electron microscopy of the normal and experimentally infected ocular surface.

Scanning and transmission electron microscopy were used to characterize the normal pup and adult mouse ocular surface. Various fixatives were examined and categorized into those which stabilize and preserve ocular mucus associated with surface corneal epithelial cells and those which do not, but allow good visualization of surface detail for scanning electron microscopy. Desquamation patterns of corneal epithelial surface cells in the mouse pup and adult were examined, compared with each other and with desquamation patterns originally reported for several other animal species. Once the normal cytoarchitecture of the corneal surface and its associated ocular mucus was established for the mouse pup and the adult animal, the murine ocular response to P. aeruginosa infection was studied. Those studies revealed that in the pup, after inoculation of bacteria beneath the eyelid, with no corneal scarification, organisms adhered preferentially to young surface cells and quickly penetrated the corneal and conjunctival epithelium. In contrast, scarification of the corneal surface had to precede topical bacterial inoculation for infection to occur in the adult cornea. In this model, bacteria adhered initially to the wound site and to aged cells but did not preferentially adhere to young surface cells. An extracellular virulence factor, exotoxin A, produced by the bacteria, was also examined to determine its role in P. aeruginosa pathogenesis. Studies using toxin A, have shown that it was capable of inducing epithelial and endothelial cell death and corneal necrosis in the adult scarified cornea. In the pup, where no scarification preceded toxin A challenge, little corneal epithelial damage was produced when compared with the infection model. Nonetheless, as with bacterially challenged pups, experimental toxin A treated animals died within 24 hr following toxin administration.

ADP Ribose Transferases↗

Histogenesis of the mesocortical area of the mouse telencephalon.

The histogenesis of the mesocortex of the mouse telencephalon was studied by plotting the progress of neuron release on reconstructions of the medial pallial wall. Histological changes were correlated with cell birth date using data obtained from autoradiographs of mice pulse-labelled with tritiated thymidine during the prenatal period of neuron birth. It was found that neuron release for this area began rostrally at about E12-E13 and spread rapidly from this origin in a caudal direction across the medial wall. Neurons accumulating in the intermediate layer were at first more or less equally spaced. About E14, neurons in the outer intermediate layer began to line up to form a 'mesocortical plate'. This plate was formed from older nuclei and therefore overlay a deeper intermediate layer composed of younger cells. The mesocortex continued to develop by progressive withdrawal of younger cells from the deep intermediate layer into more superficial layers of the definitive cortex. In most of the mesocortical area, however, this original pattern was superseded by release of neuron generations which migrated directly to the outer intermediate layer to form a plate of densely packed immature neurons. This population was continuous with a similar population forming the isocortical plate of the lateral telencephalic wall. It was postulated that the wave of neuron birth and release which gave rise to the isocortical plate was propagated beyond the isocortical boundary into mesocortical territory as far as the boundaries of the subiculum, indusium griseum and anterior hippocampal rudiment.

Animals↗