SEARCH · PubMed Health

Results for “PLETHORA”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 289 records · Page 16Linked to original sources

PubMed2002

Explaining neurocognitive aging: is one factor enough?

As an introduction to the special issue on neurocognitive factors underlying age effects, we discuss a number of recent developments in the literature on aging. The classic distinction between generalized and process-specific cognitive changes with old age has reappeared in the distinctions between the frontal lobe hypothesis and more differentiated views of neurocognitive aging. We argue that neurological decay in the frontal cortex has important implications for cognitive control, but that the frontal lobe hypothesis does not capture the plethora of changes that characterize aging and incorrectly suggests a unitary effect.

Aged↗

PubMed2000

Toward a unified theory of narcosis: brain imaging evidence for a thalamocortical switch as the neurophysiologic basis of anesthetic-induced unconsciousness.

A unifying theory of general anesthetic-induced unconsciousness must explain the common mechanism through which various anesthetic agents produce unconsciousness. Functional-brain-imaging data obtained from 11 volunteers during general anesthesia showed specific suppression of regional thalamic and midbrain reticular formation activity across two different commonly used volatile agents. These findings are discussed in relation to findings from sleep neurophysiology and the implications of this work for consciousness research. It is hypothesized that the essential common neurophysiologic mechanism underlying anesthetic-induced unconsciousness is, as with sleep-induced unconsciousness, a hyperpolarization block of thalamocortical neurons. A model of anesthetic-induced unconsciousness is introduced to explain how the plethora of effects anesthetics have on cellular functioning ultimately all converge on a single neuroanatomic/neurophysiologic system, thus providing for a unitary physiologic theory of narcosis related to consciousness.

Adolescent↗

PubMed2002

Cytokine imbalance in non-immunological chronic disease.

Over the last decade, cytokine imbalances have been associated with a plethora of diseases. While the Th(1)/Th(2) paradigm is widely used to explain the pathogenesis of immunological diseases, the role of cytokine imbalances for non-immunological diseases is still incompletely defined. The major obstacle here is to assess the extent to which non-immunological diseases are influenced by inflammation. Non-immunological diseases cover the whole spectrum from those triggered by infection-as may be the case for Alzheimer's disease-to those where the immune system has no apparent impact at all. Examples of the latter are bone diseases, including post-menopausal osteoporosis and skeletal malformations. In between there are diseases such as intrinsic asthma and osteoarthritis where the impact of the immune system is unclear. Thus far, imbalances affecting tumour necrosis factor (TNF)-alpha and members of the interleukin (IL)-1 and the TGF superfamily have been found in association with all of these diseases. We speculate here that cytokine imbalance will be found in additional diseases and touch on the role in phylogeny of cytokines outside the immune system.

Alleles↗

PubMed1993

Complete mouse egg activation in the absence of sperm by stimulation of an exogenous G protein-coupled receptor.

Sperm-induced egg activation has several features in common with signal transduction pathways mediated by ligand-receptor-effector systems. G proteins are postulated to act as signal transducers regulating the plethora of cellular responses constituting egg activation that occur in response to sperm. We report that acetylcholine treatment of mouse eggs expressing the human m1 muscarinic receptor, a G protein-coupled receptor, results in the full complement of events of egg activation, including ZP2 to ZP2f conversion, recruitment of maternal mRNAs, pronuclear formation with subsequent DNA synthesis, cleavage to the two-cell stage, and activation of the embryonic genome. The induction of a full complement of sperm-induced egg activation events by ACh in the absence of sperm strongly suggests that sperm-induced egg activation is mediated by egg G proteins.

Acetylcholine↗

PubMed2000

Genes in the first and fourth inversions of the mouse t complex synergistically mediate sperm capacitation and interactions with the oocyte.

The t haplotypes (t) are recent evolutionary derivatives of an alternate form of the mouse t complex region located at the proximal end of chromosome 17. This variant form of approximately 1% of the mouse genome is a source of mutations altering numerous sperm functions crucial for fertilization. Males that carry two t haplotypes (t/t) are invariably sterile. t haplotypes contain four inversions relative to the wild-type t complex (+), so that in matings involving a +/t heterozygote, t is usually transmitted as a single unit. However, rare recombinants have been recovered, which carry only part of the t genotype and express only some of the t-dependent phenotypes. Use of these partial t haplotypes in genetic crosses has resulted in the general location of the two major t male sterility factors, S1 and S2, within inversions 1 and 4, respectively. Since sterility can result from a plethora of sperm defects, we have made a detailed study of various functional parameters of sperm from mice carrying S1 or S2 heterozygously or homozygously or in combination. Both S1 and S2 contain mutations altering sperm functions, including motility, capacitation, binding to the zona pellucida, binding to the oocyte membrane, and penetration of the zona pellucida-free oocyte. Therefore it seems clear that each of these factors contains multiple genes contributing to sterility. Furthermore, our results indicate that genes within S1 interact with genes in S2 for all sperm functions examined. However, S1 and S2 genes affecting motility interact in a purely additive fashion, while S1 and S2 genes affecting most other sperm characteristics interact in a synergistic manner. Additionally, the patterns of synergism between S1 and S2 for abnormalities in capacitation, sperm-oolemma binding, and zona-free oocyte penetration are nearly identical. This suggests that these three defects are caused by mutation of the same gene within each sterility factor. These findings will not only be instrumental in matching the various t haplotype sperm defects to candidate genes for S1 and S2, but will facilitate a more comprehensive understanding of the cellular and genetic mechanisms underlying t haplotype male sterility.

Acrosome↗

PubMed2002

It takes guts: the Drosophila hindgut as a model system for organogenesis.

The Drosophila hindgut is fruitful territory for investigation of events common to many types of organogenesis. The development of the Drosophila hindgut provides, in microcosm, a genetic model system for studying processes such as establishment (patterning) of an epithelial primordium, its internalization by gastrulation, development of left--right asymmetric looping, patterning in both the anteroposterior and dorsoventral axes, innervation, investment of an epithelium with mesoderm, reciprocal epitheliomesenchymal interactions, cell shape change, and cell rearrangement. We review the genetic control of these processes during development of the Drosophila hindgut, and compare these to related processes in other bilaterians, particularly vertebrates. We propose that caudal/Cdx, brachyenteron/Brachyury, fork head/HNF-3, and wingless/Wnt constitute a conserved "cassette" of genes expressed in the blastopore and later in the gut, involved in posterior patterning, cell rearrangement, and gut maintenance. Elongation of the internalized Drosophila hindgut primordium is similar to elongation of the archenteron and also of the entire embryonic axis (both during and after gastrulation), as well as of various tubules (e.g., nephric ducts, Malpighian tubules), as it is driven by cell rearrangement. The genes drumstick, bowl, and lines (which encode putative transcriptional regulators) are required for this cell rearrangement, as well as for spatially localized gene expression required to establish the three morphologically distinct subregions of the hindgut. Expression of signaling molecules regulated by drumstick, bowl, and lines, in particular of the JAK/STAT activator Unpaired at the hindgut anterior, may play a role in controlling hindgut cell rearrangement. Other cell signaling molecules expressed in the hindgut epithelium are required to establish its normal size (Dpp and Hh), and to establish and maintain the hindgut visceral mesoderm (Wg and Hh). Both maternal gene activity and zygotic gene activity are required for asymmetric left--right looping of the hindgut. Some of the same genes (caudal and brachyenteron) required for embryonic hindgut development also act during pupation to construct a new hindgut from imaginal cells. Application of the plethora of genetic techniques available in Drosophila, including forward genetic screens, should identify additional genes controlling hindgut development and thus shed light on a variety of common morphogenetic processes.

Animals↗

PubMed2000

The Electroencephalogram in Attention Deficit-Hyperactivity Disorder: Emphasis on Epileptiform Discharges.

This study dealt with the electroencephalograms (EEGs) of 176 children with attention deficit-hyperactivity disorder (ADHD). Of special interest were the patients who had in their EEG some type of spike activity (spike group), in contrast with those without such activity (control group). In the entire group, 27.8% were completely normal and an additional 18.8% had positive spikes as their only finding. Definite noncontroversial, epileptiform activity was seen in 30.1%, mainly focal (usually occipital or temporal), less often generalized, with bilaterally synchronous spike and waves complexes seen in 11 children. Extreme spindles or diffuse slow waves occurred only in the spike group (one exception in each) and slow wave abnormalities (mainly frontal or temporal), nearly always mild in degree, were seen mainly in the spike group. These different findings suggest that ADHD is a condition often with organic changes in the form of EEG abnormality, at times with epileptiform activity that could contribute to a deficit in attention or a plethora of movements.

Journal Article↗

PubMed1997

The retinoblastoma protein pathway in cell cycle control and cancer.

Recent discoveries in diverse fields of biomedical research have merged to reveal the molecular basis of cell cycle control and a critical role of subverting this homeostatic mechanism in cancer development. At the heart of these processes lies a late G1 checkpoint governed by the "RB pathway" whose molecular composition, functions, and cancer-associated defects are briefly evaluated in this review. This exciting new knowledge raises a plethora of conceptual issues in cell biology, with potential practical implications for biotechnology and medicine.

Animals↗

PubMed1999

The Phenomena of Proton Transfer from Catalytic Oxides.

Chemical processes that occur at the particle aqueous interface are properly termed colloidal when the particle is a material where one or more of its three dimensions lies within the range of 1-1000 nm. Nanoparticles which include porous materials and nanostructures that meet this requirement have been the subject of investigation from researchers from a variety of disciplines and their studies have been reported in the Journal of Colloid and Interface Science as well as other archival journals for many years. The chemical process of charge development on colloidal particles is, in general, determined by a plethora of complex physico-chemical properties of the particles' surfaces exposed to the surrounding aqueous environment. The existence of surface charge plays an essential role in the dispersity, flocculation properties, ion exchange capacity, dissolution, and deposition of cations and anions of synthetic and natural materials. In particular, recent advances in catalytic science have demonstrated that the "black art" of catalyst preparation does have a scientific basis. The objective of this article is to demonstrate that surface charge development (a consequence of proton transfer) as a function of pH, the so-called master variable, can identify specific domains of charge maxima. It is found that the number and strength of charged sites can be correlated with the catalytic properties of the studied materials, even though the reaction conditions are significantly different from those under which the surface charge was measured. Such findings are essential for the establishment of design and construction protocols and prediction of the performance of catalysts. Copyright 1999 Academic Press.

Journal Article↗

PubMed1998

The molecular mechanism of pneumolysin, a virulence factor from Streptococcus pneumoniae.

Pneumolysin, a member of the thiol-activated cytolysin family of toxins, is a virulence factor from the Gram-positive bacterium Streptococcus pneumoniae. The toxin forms large oligomeric pores in cholesterol-containing membranes of eukaryotic cells. A plethora of biochemical and mutagenesis data have been published on pneumolysin, since its initial characterization in the 1930s. Here we present an homology model of the monomeric and oligomeric forms of pneumolysin based on the recently determined crystal structure of perfringolysin O and electron microscopy data. A feature of the model is a striking electronegative surface on parts of pneumolysin that may reflect its cytosolic location in the bacterial cell. The models provide a molecular basis for understanding the effects of published mutagenesis and biochemical modifications on the toxic activity of pneumolysin. In addition, spectroscopic data are presented that shed new light on pneumolysin activity and have guided us to hypothesise a detailed model of membrane insertion. These data show that the environment of some tryptophan residues changes on insertion and/or pore formation. In particular, spectroscopic analysis of a tryptophan mutant, W433F, suggests it is the residue mainly responsible for the observed effects. Furthermore, there is no change in the secondary structure content when the toxin inserts into membranes. Finally, the basis of the very low activity shown by a pneumolysin molecule from another strain of S. pneumoniae may be due to the movements of a key domain-domain interface. The molecular basis of pneumolysin-induced complement activation may be related to the structural similarity of one of the domains of pneumolysin to Fc, rather than the presumed homology of the toxin to C-reactive protein as previously suggested.

Amino Acid Sequence↗

PubMedDate not supplied

Folic acid: nutritional biochemistry, molecular biology, and role in disease processes.

This paper reviews the chemistry, metabolism, and molecular biology of folic acid, with a particular emphasis on how it is, or may be, involved in many disease processes. Folic acid prevents neural tube defects like spina bifida, while its ability to lower homocysteine suggests it might have a positive influence on cardiovascular disease. A role for this B vitamin in maintaining good health may, in fact, extend beyond these clinical conditions to encompass other birth defects, several types of cancer, dementia, affective disorders, Down's syndrome, and serious conditions affecting pregnancy outcome. The effect of folate in these conditions can be explained largely within the context of folate-dependent pathways leading to methionine and nucleotide biosynthesis, and genetic variability resulting from a number of common polymorphisms of folate-dependent enzymes involved in the homocysteine remethylation cycle. Allelic variants of folate genes that have a high frequency in the population, and that may play a role in disease formation include 677C --> T-MTHFR, 1298A --> C-MTHFR, 2756A --> G-MetSyn, and 66A --> G-MSR. Future work will probably uncover further polymorphisms of folate metabolism, and lead to a wider understanding of the interaction between this essential nutrient and the many genes which underpin its enzymatic utilization in a plethora of critical biosynthetic reactions, and which, under adverse nutritional conditions, may promote disease.

Biological Transport, Active↗

PubMed1995

Health promotion and osteoporosis prevention among postmenopausal women.

BACKGROUND: Although there is a plethora of literature about osteoporosis, little is known about the attitudinal variables that may predict osteoporosis-preventive behaviors (OPBs) among postmenopausal women. This study examined the relationship between variables from the Health Promotion Model (HPM) and OPBs of calcium intake, exercise participation, and taking of estrogen/hormone replacement therapy (ERT/HRT). METHODS: One hundred women completed measures of benefits and barriers to calcium intake, exercise participation, ERT/HRT usage; self-efficacy; control of health; importance of health; and health status. Participants also reported their actual calcium intake, exercise participation, and use of ERT/HRT: RESULTS: Participants consumed an average of 1,243 mg of calcium from milk, yogurt, calcium-rich foods, and supplements; 81% participated in weight-bearing and resistant training exercise but on an irregular basis; and 31% were users of ERT/HRT at the time of data collection. There were significant relationships between some of the HPM variables and calcium intake and exercise participation. There was a significant difference between past and current users of ERT regarding benefits and barriers to taking hormones. Hormone users reported higher calcium intake and greater exercise participation than nonusers. CONCLUSION: There is early evidence that variables of the HPM are associated with OPBs. After continued testing, intervention programs for osteoporosis prevention may use variables of the HPM as a theoretical base for behavior changes.

Activities of Daily Living↗

PubMed1999

Homogeneous purification of human recombinant GST-Akt/PKB from Sf9 cells.

The plethora of extracellular stimuli modulating the status of a cell results in the engagement of relatively few pathways responsible for transducing signals to the interior of the cell. One such pathway is the activation of phosphatidylinositol 3-kinase (PI-3K), which results in the generation of a membrane-restricted second messenger, polyphosphatidylinositide 3'-phosphate. Among the enzymes activated by 3'-phosphorylated inositol lipids is Akt/protein kinase B (PKB). Here we describe a protocol for the expression and one-step purification of human recombinant GST-PKB in Sf9 cells. This scheme allows generating large amounts of homogeneously purified GST-PKB with high specific activity to be employed in high-throughput screening or structural studies.

Animals↗

PubMed1998

A multigeneration study to ascertain the toxicological effects of Great Lakes salmon fed to rats: study overview and design.

Fish from the Great Lakes can be contaminated with a plethora of industrial, agricultural, and environmental chemicals. These chemicals have been associated with reproductive and other toxicological effects in fish and fish-eating birds found in the Great Lakes basin. To obtain more insight into this association, several laboratory studies have been undertaken wherein fish have been incorporated into the experimental diets to determine the effect of their ingestion upon the test animals. In addition, several human epidemiological studies have found correlations between Great Lakes fish consumption and effects in neonates which have been attributed to polychlorinated biphenyls without any appreciable consideration as to what synergistic or antagonistic effects other chemicals or heavy metals may or may not have contributed to the observed findings. Herein is presented the design of a two-generation feeding-reproduction study that incorporated lyophilized chinook salmon (Oncorhynchus tsawytscha) fillets into the diets of Sprague-Dawley rats. The findings of this study will be presented in the sections which follow.

Animal Feed↗

PubMed1997

Control of tyrosine hydroxylase gene expression in chromaffin and PC12 cells.

Chromaffin and PC12 cells were used to elucidate mechanisms of stimulation of gene expression of tyrosine hydroxylase (TH), the pivotal enzyme in catecholamine biosynthesis. A plethora of treatments elevate TH gene expression. Elevated cAMP triggers increased TH gene expression, primarily by an increase in mRNA transcription. Although a variety of treatments that elevate [Ca(2+)](i), increase TH transcription, there are important differences among them, indicating different calcium signalling pathways in regulating TH gene expression acting at the CRE/CaRE (cyclic AMP/calcium response element). Several complexes, such as ATF-1/jun and CREB/AT-1 heterodimers bind this element. Activation of protein kinase C by phorbol esters, NGF and EGF activate TH transcription through the AP-1 site. TH transcription is also stimulated by glucocorticoids, increased cell density, hypoxia, and several other treatments. In some instances, post-transcriptional mechanisms also contribute to the intricate fine tuning of regulation of TH gene expression.

Journal Article↗

PubMed1998

Diet restriction enhances compensatory liver tissue repair and survival following administration of lethal dose of thioacetamide.

Diet restriction is known to prevent a plethora of age-associated diseases including cancer. However, the effects of diet restriction on noncancer end points are not known. The objective of this study was to investigate whether diet restriction protects against hepatotoxicity of thioacetamide (TA), and if so, to investigate the underlying mechanism. Male Sprague-Dawley rats (250-275 g) were maintained on 65% of their ad libitum (AL) food consumption for a period of 3 weeks and then treated with a single low dose of 50 mg TA/kg i.p.. Plasma enzymes (ALT and SDH), hepatic glycogen levels, and 3H-thymidine incorporation into hepatocellular nuclear DNA were measured during a time course (0-120 h) after TA administration. Liver sections were examined for histopathology, and cell-cycle progression was assessed by proliferating cell nuclear antigen (PCNA) immunohistochemistry. In AL rats hepatic necrosis was evident at 12 h, peaked at 36 h, persisted up to 72 h, and was resolved by 96 h. In the diet-restricted (DR) group hepatic necrosis was observed at 12 h, peaked at 24 h, persisted till 72 h, and was resolved by 96 h. Maximal injury indicated by enzyme elevation occurred in DR rats and was approximately sixfold greater than that observed in the AL group. Histopathological examination of the liver sections revealed liver injury concordant with plasma enzyme elevations. There was a higher and sustained S-phase synthesis in the DR rats compared to AL group. S-phase stimulation was evident at 36 h, peaked at 48 h, and persisted until 96 h in the DR rats, whereas in the AL rats peak S-phase stimulation occurred at 36 h and subsided by 72 h. PCNA studies revealed a corresponding stimulation of cell-cycle progression indicating highly stimulated compensatory tissue repair. The 14-day lethality experiments (600 mg TA/kg i.p.) indicated 70% survival in the DR rats compared to 10% survival in the AL group. Although diet restriction increases hepatotoxic injury of TA, it protects from the lethal outcome by enhanced liver tissue repair. Comparison of liver injury and tissue repair employing an equitoxic dose (600 mg TA/kg in AL rats yields similar liver injury as observed with 50 mg TA/kg in DR rats) revealed that in spite of near equal injury up to 36 h, tissue repair response in DR rats is much higher. The compensatory tissue repair allows the DR rats to escape death in contrast to much lower compensation in AL rats leading to progression of liver injury culminating in death.

Animals↗

PubMed1996

Myxoma virus M-T7, a secreted homolog of the interferon-gamma receptor, is a critical virulence factor for the development of myxomatosis in European rabbits.

Myxoma virus is a leporipoxvirus of New World rabbits (Sylvilagus sp.) that induces a rapidly lethal infection known as myxomatosis in the European rabbit (Oryctolagus cuniculus). Like all poxviruses, myxoma virus encodes a plethora of proteins to circumvent or inhibit a variety of host antiviral immune mechanisms. M-T7, the most abundantly secreted protein of myxoma virus-infected cells, was originally identified as an interferon-gamma receptor homolog (Upton, Mossman, and McFadden, Science 258, 1369-1372, 1992). Here, we demonstrate that M-T7 is dispensable for virus replication in cultured cells but is a critical virulence factor for virus pathogenesis in European rabbits. Disruption of both copies of the M-T7 gene in myxoma virus was achieved by the deletion of 372 bp of M-T7 coding sequences, replacement with a selectable marker, p7.5Ecogpt, and selection of a recombinant virus (vMyxlac-T7gpt) resistant to mycophenolic acid. vMyxlac-T7gpt expressed no detectable M-T7 protein and infected cells supernatants were devoid of any detectable interferon-gamma binding activities. Immunohistochemical staining with anti-beta-galactosidase and anti-CD43 antibodies demonstrated that in vMyxlac-T7gpt-infected rabbits the loss of M-T7 not only caused a dramatic reduction in disease symptoms and viral dissemination to secondary sites, but also dramatically influenced host leukocyte behavior. Notably, primary lesions in wild-type virus infections were generally underlayed by large masses of inflammatory cells that did not effectively migrate into the dermal sites of viral replication, whereas in vMyxlac-T7gpt infections this apparent block to leukocyte influx was relieved. A second major phenotypic distinction noted for the M-T7 knockout virus was the extensive activation of lymphocytes in secondary immune organs, particularly the spleen and lymph nodes, by Day 4 of the infection. This is in stark contrast to infection by wild-type myxoma virus, which results in relatively little, if any, cellular activation of germinal centers of spleen and lymph node by Day 4. We conclude that M-T7 functions early in infection to (1) retard inflammatory cell migration into infected tissues and (2) disrupt the communication between sentinel immune cells at the site of primary virus infection in the subdermis and lymphocytes in the secondary lymphoid organs, thereby disabling the host from mounting an effective cellular immune response. To summarize, in addition to neutralizing host interferon-gamma at infected sites, we propose that M-T7 protein also modifies leukocyte traffic in the vicinity of virus lesions, thus effectively severing the link between antigen presenting cells of the infected tissue and the effector lymphocytes of the peripheral immune organs.

Animals↗

PubMed2001

Complete nucleotide sequence and analysis of a novel human papillomavirus (HPV 84) genome cloned by an overlapping PCR method.

Molecular diagnosis of human papillomaviruses (HPVs) in cervicovaginal samples reveals a plethora of known and novel HPV genomes. We describe the use of an overlapping PCR method to clone and analyze the complete genome of HPV 84 from cervicovaginal cells obtained from a 21-year-old Caucasian female with a normal Pap smear. The 7948-bp complete nucleotide sequence of HPV 84 was determined from five overlapping PCR products by sequence walking. A BLAST homology search demonstrated that HPV 84 was most closely related to HPV 61 (89%), HPV 72 (86%), and HPV 83 (85%) by nucleotide sequence analysis of the L1 open reading frame, placing it in the HPV genome homology group A3. Previously, this virus had been identified as Pap155. Based on extensive epidemiological data, HPV 84 is a highly prevalent genital papillomavirus primarily detected in normal and HIV-infected women.

Adult↗