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At least 667 records · Page 37Linked to original sources

PubMed1994

Properties of the 'neutral zone' explain polarity of retinal spreading depression.

Retinal spreading depression was evoked using low Cl- Ringer's solution and the concomitant field potentials (spreading depression potential; SDP) were recorded. The polarity of the transretinally recorded SDPs was not consistent among animal species. The SDPs recorded from carp and frog were receptor side negative, while chick and cat induced receptor side positive SDPs. According to the K+ hypothesis, the retinal SDP is generated by Müller cells responding to an increase in the extracellular K+ concentration in the inner plexiform layer. In order to clarify the relationship between the K+ increase and the polarity of the SDP, a high-K+ solution was injected at various retinal depths and the evoked potential was recorded transretinally. The neutral zone within the retina, where a change in the extracellular K+ concentration produces no net potential difference, was revealed to be near the proximal end of the retina in carp and frog, while it was located distal to the inner plexiform layer in the chick and cat. These results support the Müller cell K+ hypothesis and explain the polarity of SDPs. We conclude that the concept of the neutral zone is valuable for the investigation of the mechanism and polarity of transretinal field potentials.

Animals↗

PubMed1996

Xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy: do the genes explain the diseases?

Xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy are three distinct human syndromes associated with sensitivity to ultraviolet radiation. We review evidence that these syndromes overlap with each other and arise from mutations in genes involved in nucleotide-excision repair and RNA transcription. Attempts have been made to explain the syndromes in terms of defects in repair and transcription. These two biochemical pathways do not easily account for all the features of the syndromes. Therefore, we propose a third pathway, in which the syndromes are due, in part, to defects in a demethylation mechanism involving the excision of methylated cytosine. Perturbation of demethylation could affect the developmentally regulated expression of some genes.

Animals↗

PubMedDate not supplied

Rapid adaptation of central pathways explains the suppressed baroreflex with aging.

Aging is associated with suppressed baroreflex function. Renal sympathetic nerve activity was recorded from young (1 year) and old beagles (11 years) during a step rise in isolated carotid sinus pressure. An abrupt increase in pressure resulted in a significant and similar inhibition of efferent nerve activity in both groups, but the inhibition was not sustained in the old as compared with the young animals. The escape from sympathetic inhibition in the old could not be explained by a decline of input from sensory baroreceptor neurons. Thus the defect in the aged animals is caused by a rapid adaptation of central baroreflex neurons to the baroreceptor input instead of a lack of responsiveness of these neurons, suggesting a functional rather than a structural impairment.

Adaptation, Physiological↗

PubMed1993

HLA-DQ2 second-domain polymorphisms may explain increased trans-associated risk in celiac disease and dermatitis herpetiformis.

Sequence polymorphism in the DQ2 beta chain was investigated in 80 Caucasoid patients with CD, 23 patients with DH, and 64 healthy controls. A set of amplification primers were designed to amplify a 281-bp region between amino acids 95 and 135 encoding the second domain of the DQ beta chain gene. A polymorphism at amino acid 135 was shown to distinguish DR3 and DR7 haplotypes. Two SSO probes were designed to identify amino acid sequences (133-135) RND (DR3-DQ2) and RNG (DR7-DQ2). To establish whether polymorphism existed elsewhere in the second-domain sequence, which could explain the migratory characteristics of the CD-associated DR3-DQ2 beta-chain reported by Roep et al. DQB1 second-domain PCR products were sequenced from the genomic DNA of three CD patients. The results showed that the polymorphism at amino acid 135 distinguishing DR3 and DR7 haplotypes was present in CD, DH patients, or normal controls of the appropriate DR and DQ genotypes by oligonucleotide hybridization. Cloning and sequencing of DQB1 second domains of three CD patients (two DR3,3 and one DR3,7) gave normal sequences expected from their genotypes. No specific polymorphism of DQB1 second domains on CD-associated DR3 haplotypes distinguishes them from normal DR3 haplotypes. We conclude that individuals positive for the DR3,7 genotype have the potential to express a unique trans-encoded heterodimer with enhanced ability to predispose people to CD.

Amino Acid Sequence↗

PubMed1995

Explaining rising mortality among men in eastern Europe.

Since the mid-1960s, rates of premature mortality have increased among men in all Eastern European countries, giving rise to an East-West health divide. The paper examines the existing data concerning the possible role of levels of smoking, fats consumption and/or environmental factors in explaining this phenomenon. An overview is offered of the key ways in which social experience in Eastern Europe has diverged from that in the West and it is argued that such an overview is pre-requisite for understanding the deteriorating health of men in the East. The importance of the 'incongruity' between aspirations and the means of achieving them is highlighted, as is the centrality of family-based coping strategies. It is argued that the devaluing of the public sphere and valorization of the private domain contribute to the greater health vulnerability of men under in Eastern Europe. The importance of the private sphere is reflected in the fact that the rise of premature male mortality has been overwhelmingly concentrated in the non-married population in the East European countries for which data is currently available.

Adult↗

PubMed1989

Failure of antipsychotic drug dose to explain abnormal diurnal weight gain among 129 chronically psychotic inpatients.

1. The diurnal weight gain was found to be abnormal among 129 chronically psychotic inpatients. 2. The patients were weighed at 7 a.m. and 4 p.m. weekly for three weeks. We normalized the diurnal weight gain (NDWG) as a percentage by subtracting the 7 a.m. weight from the 4 p.m. weight, multiplying the difference by 100, and then dividing the result by the 7 a.m. weight. 3. NDWG was 2.2 +/- 1.5 percent for 87 male patients compared (p less than .0001) with .53 +/- .41 for 14 male controls. 4. NDWG was 1.8 +/- 1.0 percent for 42 female patients compared (p less than .0001) with .49 +/- .30 for 15 female controls. 5. Seventy percent of male and female patients had NDWG values greater than two standard deviations above the mean values of controls. 6. Differences in age, sex, morning weight, antipsychotic drugs, lithium, carbamazepine, phenytoin, blood pressure, and pulse did not explain these findings.

Adult↗

PubMed1996

The hypercube structure of the genetic code explains conservative and non-conservative aminoacid substitutions in vivo and in vitro.

A representation of the genetic code as a six-dimensional Boolean hypercube is described. This structure is the result of the hierarchical order of the interaction energies of the bases in codon-anticodon recognition. In this paper it is applied to study molecular evolution in vivo and in vitro. In the first case we compared aligned positions in homologous protein sequences and found two different behaviors: (a) There are sites in which the different amino acids may be explained by one or two 'attractor nodes' (coding for the dominating amino acid(s)) and their one-bit neighbors in the codon hypercube; and (b) There are sites in which the amino acids correspond to codons located in closed paths in the hypercube. In the second case we studied the 'Sexual PCR'1 experiment described by Stemmer [Stemmer (1994)] and found that the success of this combination of usual PCR and recombination is in part due to the Gray code structure of the genetic code.

Amino Acids↗

PubMed1993

Transcription rate of the follicle stimulating hormone (FSH) beta subunit gene is reduced by inhibin in sheep but this does not fully explain the decrease in mRNA.

Studies were conducted in vitro and in vivo to determine whether or not inhibin affects the transcription rate of the gene for the beta subunit of follicle stimulating hormone (FSH beta). Pituitary cells in primary culture were incubated with 0-3000 milli-units/ml inhibin; a dose-related decrement in mRNA was obtained but a parallel effect was not observed for the transcription rate of the FSH beta gene in a nuclear run-on experiment. To determine effects in vivo, ovariectomized ewes were treated with saline (group 1), 75 micrograms inhibin 6 h before slaughter (group 2), inhibin 6 h and 12 h before slaughter (group 3) or inhibin 12 h before slaughter (group 4). In samples taken each 2 h, plasma FSH levels were seen to be maximally reduced 6 h after a single injection of inhibin; at this time mRNA levels were reduced up to 100% whereas FSH beta gene transcription rate was reduced by 50%. A second injection at 6 h (group 3) caused a further reduction in plasma FSH levels with no additional effect on transcription rate. In those sheep killed 12 h after a single inhibin injection, transcription rate for the FSH beta gene, cytoplasmic mRNA levels and plasma FSH concentrations had recovered. These studies show that the rapid effect of inhibin on FSH beta mRNA levels may be due, in part, to an effect on transcription rate of the FSH beta gene. An additional mechanism is required, however, to fully explain the inhibin effect on FSH beta mRNA levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Difference in monoamine oxidase B activity between C57 black and albino NMRI mouse strains may explain differential effects of the neurotoxin MPTP.

Monoamine oxidase B (MAO-B) is the key enzyme in the conversion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP) to N-methyl-4-phenyl-pyridinium ion (MPP+) which causes degeneration of dopaminergic nigral neurons. Using a histochemical tetrazolium method for MAO-B with tyramine as substrate and chlorgyline for the inhibition of MAO-A, black C57 mice were found to have a higher brain MAO-B activity than similar aged albino NMRI mice. The difference, which was in general density rather than distribution, included the basal ganglia and the substantia nigra. The higher activity in C57 mice may explain differences in the susceptibility to MPTP.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1995

Neurogenesis is absent in the brains of adult honey bees and does not explain behavioral neuroplasticity.

The mushroom bodies, the insect brain structures most often associated with learning, exhibit structural plasticity during adult behavioral development in honey bees. We have investigated whether adult neurogenesis contributes to the plasticity of the mushroom bodies by labeling the DNA of replicating cells with 5-bromo-2'-deoxyuridine (BrdU). Immunocytochemical analysis of brain sections from bees fed or injected with BrdU as well as from bees treated in vitro with BrdU revealed no labeled neuronal nuclei, regardless of age or behavioral status of the worker bee (1-day old, nurse, or forager). Our results demonstrate that neurogenesis in the adult bee brain is a rare event, if it occurs at all. Therefore, the structural changes observed in the bee brain during adult behavioral development must be explained by developmental processes other than neurogenesis.

Animals↗

PubMed1991

A hypothetical model to explain the 'termination' of chronic myeloid leukemia into blastic crisis.

Chronic myeloid leukemia is characterised by two discrete phases, a 'benign' phase which terminates into an 'acute' phase. Various explanations have been given to explain the cause of 'blastic' crisis in CML. But the consistency and regularity with which blast crisis occurs and the irregularity with which the factors which are ascribed to cause it (e.g. additional chromosomal abnormalities, change in bcr/abl rearrangement, etc. occur, suggests that CML-BC is not a stochastic process in the natural history of CML but is predetermined at the time of the first mutation in the stem cell. A hypothetical model is put forward proposing this. Different points supporting the model are discussed. The most important implication of this model would be to provide an insight that should lead to the development of more selective and appropriate treatment strategies for this disease.

Blast Crisis↗

PubMed1991

Smoker's melanosis may explain the lower hearing loss and lower frequency of Parkinson's disease found among tobacco smokers--a new hypothesis.

A new hypothesis is presented explaining the preventive effect of tobacco smoking found on noise induced hearing loss and on the frequency of Parkinson's disease. The hypothesis is based on the finding of a melanocyte stimulation of tobacco smoking in the human oral mucosa, resulting in a higher melanin content in the epithelial cells, and a higher frequency of visible oral melanin pigmentation--smoker's melanosis. The preventive influence of smoking found in the cochlea and substantia nigra may also be due to a higher melanin content and to the ability of melanin to strongly bind specific chemical agents for a long time. Melanin may in this way act as a scavenger against cell toxic factors in these organs.

Hearing Loss, Noise-Induced↗

PubMed1986

In vivo dimerization of cauliflower mosaic virus DNA can explain recombination.

Pairs of heterologous cauliflower mosaic virus (CaMV) genomes cloned in pBR322, one having a defective genome and both restricted at the same pBR322 cloning site, generate recombinant molecules in infected cells when co-inoculated on plants. Analysis of the restriction pattern of the isolated recombinant CaMV DNAs indicated that the intergenomic recombination may be explained by dimerization of two heterologous CaMV molecules and transcription into a hybrid 35S RNA responsible for replication of the recombinant genomes.

Base Sequence↗

PubMed1994

Molecular modelling of cytochrome CYP1A1: a putative access channel explains differences in induction potency between the isomers benzo(a)pyrene and benzo(e)pyrene, and 2- and 4-acetylaminofluorene.

The present studies were undertaken to provide a rationale for the observation that benzo(a)pyrene and 2-acetylaminofluorene induce the hepatic CYP1A1 protein, whereas their non-carcinogenic isomers benzo(e)pyrene and 4-acetylaminofluorene are, at best, relatively very weak inducers. Using amino acid sequence alignment, a molecular model of the CYP1A1 was constructed by analogy to CYP101, the bacterial protein for which the 3-dimensional structure is known from X-ray crystallographic analysis. The putative structure of the active site of the CYP1A1 protein shows the presence of two phenylalanine residues preferentially aligned in parallel orientation, presumably functioning as a 'sieve' for planar molecules, the established substrates of CYP1A1. The molecular dimensions of this putative access channel show a width and depth of 8.321 and 3.261 A, respectively. The width of 4-acetylaminofluorene, 8.794 A, and benzo(e)pyrene, 9.153 A, precludes their passage through this channel access in contrast to benzo(a)pyrene and 2-acetylaminofluorene having a width of 7.150 and 5.283 A, respectively, explaining their difference in CYP1A1 induction potential.

2-Acetylaminofluorene↗

PubMed1986

A colloid osmotic model of macromolecular aggregation to explain tissue water loss in aging.

We have evolved from the sea, are composed mostly of water, the medium and solvent wherein most vital processes occur, and phylogenetically and ontogenetically lose water continually as we age. An embryo is about 90% water, a newborn child about 80% water, a mature adult about 70% water, an older adult about 60% water with recent work indicating that in senescence the percentage of body water is actually below 60%. The mechanisms of the water loss in aging have not been elucidated. From a theoretical point of view, there is good reason to believe that there may be profound changes in the chemical potential of intracellular and interstitial water with age due to increased macromolecular interaction or aggregation from cross linking, polymerization, insolubility, etc.; all of which are known to increase with aging. The resultant increased macromolecular solute-solute interaction would be accompanied by decreased macromolecular solute-solvent interaction, thereby causing a higher solvent (water) chemical potential. This would facilitate the loss of bound water, thereby explaining the observed losses in body water with age. The ocular lens is a microcosm of aging, in that from its nucleus to cortex, the oldest to youngest cells are concentrically arranged, as in a tree. We have developed a method to directly measure lens tissue oncotic pressure in an attempt to experimentally test the above cited hypothesis.

Aging↗

PubMed1995

How do GPs discuss subjects other than illness? Formulating and evaluating a theoretical model to explain successful and less successful approaches to discussing psychosocial issues.

A theoretical model was formed, according to grounded theory, to understand how discussions about psychosocial problems might be designed. It was used in 19 videotaped consultations where it was considered relevant for the physician to take up psychosocial issues. 'Concern' i.e. that the patient could express that which was most pressing, was used as an indicator of outcome. A uniform pattern was observed in those cases where the patients expressed 'concern', in that the physician encouraged the patient by using open-ended questions, by following up the information received, and by having an empathic approach. On the other hand, in consultations where 'concern' was not expressed, it was noticed that the physician often asked close-ended, leading or negative questions, thus putting an end to the dialogue and, as a consequence, to the follow-up phase. Important therapeutic skills would appear to be the ability to reassure and support the patient as well as to be able to explain the connection between the patient's symptoms and psychosocial problems, rather than to solve these problems.

Adult↗

PubMedDate not supplied

Human liver alcohol dehydrogenase: the unique properties of the "atypical" isoenzyme beta 2 beta 2-Bern can be explained by a single base mutation.

Two allelic variant alcohol dehydrogenase isoenzymes, beta 2 beta 2-Bern and beta 1 beta 1, coded by the ADH2 locus, were isolated from human livers of Caucasian origin. They represent the "atypical" and "typical" phenotype, respectively. beta 2 beta 2-Bern has a higher specific activity and a lower pH-optimum, has a higher kM for NAD+, is less susceptible to inactivation by iodoacetate, and cannot be activated with chloride ions. In order to define the structural basis for these properties, we determined the amino acid sequence difference between the beta 2-Bern and the beta 1 polypeptide chains. Peptides were prepared by cleavages with trypsin and CNBr, and were purified by exclusion chromatography and reverse phase high performance liquid chromatography. The structural analysis showed that beta 2-Bern differs at only one position from beta 1: Arg-47 in beta 1 is substituted for His-47 in beta 2-Bern. This exchange, which is identical to that reported for the beta 2-Oriental chain, alters the binding of the pyrophosphate group of the coenzyme NAD(H), and also that of iodoacetate, thus explaining the observed differences between beta 2 beta 2-Bern and beta 1 beta 1.

Alcohol Oxidoreductases↗

PubMed1994

Subunit composition at the single-cell level explains functional properties of a glutamate-gated channel.

The diversity of known glutamate-gated channels has been markedly increased by the discovery of multiple subunits and their spliced and edited variants. These subunits can potentially form different oligomeric complexes with diverging properties. A crucial question is therefore to determine the actual subunit composition of naturally occurring glutamate receptors. We have coupled patch-clamp recordings and reverse transcription followed by PCR amplification to correlate the presence of mRNAs for each subunit and the functional properties of native glutamate receptors at the single-cell level. In a homogeneous population of functionally identified hippocampal neurons (type II) in culture bearing a glutamate receptor of the AMPA subtype with a high calcium permeability, we found that, among the multiple subunits, only two, the flop forms of GluR1 and GluR4, were expressed. In particular, GluR2 was never detected. This composition explains the uncommon properties of AMPA receptors in type II neurons.

Animals↗