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Stochastic model of hysteresis

The methods of the probability theory have been used in order to build up a model of hysteresis which is different from the well-known Preisach model. It is assumed that the system consists of large number of abstract particles in which the variation of an external control parameter (e.g., the magnetic field) may result in transitions between two states S((+)) and S((-)). The state of a particle is characterized by the value +1 or -1 of a random variable (e.g., the magnetization direction parallel or antiparallel to the magnetic field). The transitions are governed by two further random variables corresponding to the S((-))-->S((+)) and the S((+))-->S((-)) transitions (e.g., "up switching" and "down switching magnetic field"). The method presented here makes it possible to calculate the probability distribution and consequently the expectation value of the number of particles in the S((+)) (or S((-))) state for both increasing and decreasing parameter values, i. e., the hysteresis curves of the transitions can be determined. It turns out that the reversal points of the control parameter are Markov points which determine the stochastic evolution of the process. It has been shown that the branches of the hysteresis loop are converging to fixed limit curves when the number of cyclic back-and-forth variations of the control parameter between two consecutive reversal points is large enough. This convergence to limit curves gives a clear explanation of the accommodation process. The accommodated minor loops show the return-point memory property but this property is obviously absent in the case of nonaccommodated minor loops which are not congruent and generally not closed. In contrast to the traditional Preisach model the reversal point susceptibilities are nonzero finite values. The stochastic model can provide a surprisingly good approximation of the Raylaigh quadratic law when the external parameter varies between two sufficiently small values. The practical benefits of the model can be seen in the numerical analysis of the derived equations. On one hand the calculated curves are in good qualitative agreement with the experimental observations and on the other hand, the estimation of the joint distribution function of the up and down switching fields can be performed by using the measured hysteresis curves.

Journal Article↗

Meningioma: a cytogenetic model of a complex benign human tumor, including data on 394 karyotyped cases.

Meningioma is the most frequent tumor of neuroectodermal origin in humans. It is usually benign. Only a minority of cases shows progression to an anaplastic tumor (WHO grade II and III). Meningioma is generally a sporadic tumor. Multiple and familial cases are rare and mostly associated with (hereditary) neurofibromatosis 2 (NF2). Meningiomas show an unexpectedly high recurrence rate. Also, completely removed low-grade tumors can recur. Recurrence and multiplicity are correlated with the formation of a peritumoral edema. On the cytogenetic level, meningioma is the best-studied tumor in humans. Grade I tumors show either uniform monosomy 22 or a diploid karyotype. The majority of high-grade, but only a minority of low-grade, meningiomas show loss of merlin, a cytoskeleton-cytoplasm-linker protein. Merlin is the product of the NF2 gene located on chromosome 22. A second tumor suppressor gene on chromosome 22 has not yet been detected. In contrast to other solid tumors, progression of meningiomas is correlated with increasing hypodiploidy, showing characteristic clonal evolutions that mostly include chromosomes 14, 18, and 19 and, more rarely, 6 and 10. Structural aberrations are infrequent, except for the loss of the short arm of chromosome 1, which appears to be the decisive step for anaplastic growth. Comparative histochemical and molecular cytogenetic studies point to the alkaline phosphatase gene (ALPL, liver-bone-kidney type) located on 1p36.1-->p34 as a candidate tumor suppressor gene. A model is proposed that tries to explain - with a minimum number of essential steps - the origin, progression, infiltration, and recurrence of meningiomas.

Alkaline Phosphatase↗

Saccharin- or quinine-induced changes in the rat pups following prolonged ingestion by the dam.

Effects presumably induced by a chronic free ingestion of saccharin (0.40 mg/ml) or of quinine (0.25 mg/ml) by female rats during the pregestative, gestative and lactating periods were investigated in the ensuing progeny. Preweaned pups were studied from birth up to weaning (21 days of age) by means of selected gross behavioral tests. The saccharin litters were mainly characterized by a slowering in the body growth evolution. The quinine pups demonstrate several physical anomalies: (1) congenital malformations in 5% of the animals; (2) a significantly reduced birth weight followed by a persistent growth retardation, and (3) a significant delay in the teeth eruption (1.6 and 2.6 days) and in the eye openings (1.6 days). In comparison to the untreated offspring, the saccharin pups showed minor effects whereas quinine-exposed rats were clearly impaired in several features of the postnatal physical development. Therefore, the addition of the sweetener to morphine solution may be convenient for the voluntary oral consumption of the narcotic. Conversely, quinine, used to habituate animals to drinking bitter solutions, has to be rejected in this narcotization procedure as being a harmful agent to the growing rat.

Abnormalities, Drug-Induced↗

Prevention of trauma-induced neurodegeneration in infant rat brain.

Recent evidence implicates the endogenous excitatory neurotransmitters, glutamate (Glu) and aspartate, in the pathophysiology of traumatic injury in the adult CNS, but it is not known whether similar excitotoxic mechanisms mediate traumatic injury in the immature CNS. Therefore, we developed a model of brain contusion injury in infant rats and used this model to study the nature and evolution of the acute cytopathologic changes and to evaluate the ability of Glu receptor antagonists to protect the immature brain against such changes. Seven-day-old rat pups were subjected to contusion injury and were killed 0, 0.5, 1, 2, 4, and 6 h later for histologic evaluation of the brain. Physical tearing of the dura and minor disruption of underlying brain tissue was noted at 0 h. At 30 min a discrete zone of neuronal necrosis began to appear at the border of the trauma site; this zone progressively expanded over a period of 4 h. The cytopathologic changes closely resembled the type of changes Glu is known to cause; these changes consisted of swollen dendrites, degenerating neurons with pyknotic nuclei and markedly swollen cytoplasm, and dark cells with vacuolated cytoplasm. The noncompetitive N-methyl-D-aspartate (NMDA) antagonist, dizocilpine maleate, when administered 30 min before or 1 h after trauma, significantly attenuated the lesion. The competitive NMDA antagonist, 3-((-2)-carboxypiperazine-4-yl)-propyl-1-phosphonate, was also neuroprotective. The alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate/kainate receptor antagonist 2,3-dihydro-6-nitro-7-sulfamoyl-benzo(f)quinoxaline did not significantly suppress the lesion when given as three treatments (30 mg/kg each) 30 min before plus 15 and 75 min after the insult. These findings suggest that traumatic injury in the infant rat brain is mediated by endogenous excitotoxins (Glu and aspartate) acting at NMDA receptors and can be substantially mitigated by timely treatment with NMDA receptor antagonists.

Animals↗

Fatty acid synthase-catalyzed de novo fatty acid biosynthesis: from anabolic-energy-storage pathway in normal tissues to jack-of-all-trades in cancer cells.

In 1994, Kuhajda and colleagues unambiguously identified the oncogenic antigen-519, a prognostic molecule found in breast cancer patients with markedly worsened prognosis, as fatty acid synthase (FAS),the key enzyme for the de novo fatty acid biosynthesis. It now appears that human carcinomas and their pre-neoplastic lesions constitutively over express FAS and undergo significant endogenous fatty acid biosynthesis. Moreover, FAS blockade specifically induces apoptotic cancer cell death and prolongs survival of cancer xenograft hosts. Therefore, FAS signaling seems to play a central role in the maintenance of the malignant phenotype by enhancing cancer cell survival and proliferation. This review documents the rapidly changing perspectives on the function of FAS in cancer biology. First, we describe molecular mechanism by which aberrant transduction cascades driven by oncogenic changes subvert the down-regulatory effects of dietary fatty acids, resulting in tumor-associated FAS insensitivity to nutritional signals. Second, we speculate von the putative function that hypoxia can play as the epigenetic factor that triggers and maintains FAS overexpression in cancer cells by inducing changes in gene expression and in metabolism for survival. Third, we explore the role that FAS exhibits in cancer evolution by specifically regulating cancer-related proteins such as Her-2/neu oncogene and estrogen receptor. Finally, we reveal previously unrecognized functions of FAS on the response of cancer cells to chemo-,endocrine-,and immuno therapies. These findings, all together, should ultimately enhance our understanding of how FAS-dependent endogenous fatty acid metabolism, once considered a minor anabolic-energy-storage pathway in normal cells, has become a jack-of-all-trades in cancer cells.

Animals↗

Tuberous xanthoma in homozygous type II hyperlipoproteinemia. A histologic, histochemical, and electron microscopical study.

Histologic, histochemical, and ultrastructural studies of a tuberous xanthoma from a patient with homozygous type II hyperlipoproteinemia showed that all of the lipid was within histiocytic foam cells; no lipid was identified in interstitial regions or in blood vessels. Primitive mesenchymal cells, elongated perivascular and fibroblast-like cells, and lysosome-filled macrophages also were present within the xanthoma, indicating possible stages in the evolution of dermal mesenchymal cells into mature, cholesterol-rich foam cells. Morphologically, the lipid was in four different forms: large droplets, which were the dominant form, and membrane-bound crystals, concentric lamellar bodies, and ceroid. The paucity of membrane-bound lipid forms, relative to the abundant free lipid droplets, indicated that lysosomal digestion was a minor metabolic pathway for the intracellular metabolism of lipid in the xanthoma. Thus, nonlysosomal lipid storage in foam cells is a characteristic tissue response to the underlying metabolic defect in type II hyperlipoproteinemia.

Adolescent↗

The results of surgical management of extracranial internal carotid artery occlusion and stenosis.

Vascular reconstruction was attempted in 109 patients with carotid artery occlusion or stenosis. The follow-up on those with restored or improved flow was as long as nine years (average: two and one-half years).Arteriographic demonstration of lesions is mandatory. Complications were reduced by pre-arteriographic administration of anticoagulants and retrograde brachial arteriographic techniques.Although patients with stenosis are the best candidates, an attempt to restore flow in occluded vessels is warranted in all patients, except those with advanced disease or those who are drowsy and hemiplegic. Flow was restored in two-thirds of those who underwent early operation (under three days) and in one-quarter of those undergoing late operation. Even late operation restored flow in five of nine patients who presented with transient ischemic attacks.IN COMPLETED STROKES, OPERATION SHOULD BE LIMITED TO PATIENTS WITH: (1) minor strokes, (2) extensive strokes of short duration, and (3) extensive strokes of longer duration but with a worth-while outlook.When flow was restored or improved, symptoms were arrested in 93% of patients with transient ischemia, and at follow-up this result was maintained in 86%. Symptoms were arrested in 83% of those with strokes in evolution, and this was maintained at follow-up.Reconstruction combined with anticoagulant therapy of limited duration appears to be the optimal method of treatment.

Adult↗

Evolution and replacement of Candida albicans strains during recurrent vaginitis demonstrated by DNA fingerprinting.

Southern blot hybridization with the Ca3 probe and the C fragment of the Ca3 probe was used to assess the genetic relatedness of Candida albicans strains from one patient with recurrent C. albicans infection in whom the same strain was maintained, one patient in whom the infecting strain was replaced, and their male sexual partners. In the patient in whom the infecting strain was maintained, the infecting strain exhibited a minor genetic change in each successive episode of Candida vaginitis. These genetic changes occurred in the C-fragment bands of the Ca3 hybridization pattern. In the patient in whom the infecting strain was replaced by another infecting strain, a transition infection involved a genetically mixed infecting population, and the replacement strain appeared to have originated from the oral cavity of the male partner. The results demonstrate that the infecting strains of recurrent Candida vaginitis are not genetically stable, that drug treatment can result in the selection of variants of the previously infecting strain or replacement by a genetically unrelated strain, and that the male partner can be the source of a replacement strain.

Adult↗

Ribosomal RNA phylogeny of bodonid and diplonemid flagellates and the evolution of euglenozoa.

Euglenozoa is a major phylum of excavate protozoa (comprising euglenoids, kinetoplastids, and diplonemids) with highly unusual nuclear, mitochondrial, and chloroplast genomes. To improve understanding of euglenozoan evolution, we sequenced nuclear small-subunit rRNA genes from 34 bodonids (Bodo, Neobodo, Parabodo, Dimastigella-like, Rhynchobodo, Rhynchomonas, and unidentified strains), nine diplonemids (Diplonema, Rhynchopus), and a euglenoid (Entosiphon). Phylogenetic analysis reveals that diplonemids and bodonids are more diverse than previously recognised, but does not clearly establish the branching order of kinetoplastids, euglenoids, and diplonemids. Rhynchopus is holophyletic; parasitic species arose from within free-living species. Kinetoplastea (bodonids and trypanosomatids) are robustly holophyletic and comprise a major clade including all trypanosomatids and most bodonids ('core bodonids') and a very divergent minor one including Ichthyobodo. The root of the major kinetoplastid clade is probably between trypanosomatids and core bodonids. Core bodonids have three distinct subclades. Clade 1 has two distinct Rhynchobodo-like lineages; a lineage comprising Dimastigella and Rhynchomonas; and another including Cruzella and Neobodo. Clade 2 comprises Cryptobia/ Trypanoplasma, Procryptobia, and Parabodo. Clade 3 is an extensive Bodo saltans species complex. Neobodo designis is a vast genetically divergent species complex with mutually exclusive marine and freshwater subclades. Our analysis supports three phagotrophic euglenoid orders: Petalomonadida (holophyletic), Ploeotiida (probably holophyletic), Peranemida (paraphyletic).

Animals↗

Patterns of sulfated glycosaminoglycan synthesis and accumulation in hepatic granulomas induced by schistosomal infection.

We have characterized sulfated glycosaminoglycans of periovular granulomas induced in mouse liver by experimental infection with Schistosoma mansoni and determined parameters of their synthesis and accumulation by metabolic incorporation of 35S. The major component of glycosaminoglycans isolated from granulomas was dermatan sulfate and the minor component was heparan sulfate. A similar proportion was observed among newly synthesized 35S-labeled glycosaminoglycans, with a slight increase in the relative amount of heparan sulfate. Neither qualitative nor quantitative differences were observed between glycosaminoglycans isolated from granulomas of the acute and the chronic phase of the disease. In contrast, collagen content of granulomas increased eightfold during evolution of the disease from the acute to the chronic phase. It may be concluded that different mechanisms control glycosaminoglycan and collagen synthesis in schistosomal granulomas, as well as the ratio between these components in the extracellular matrix. This is consistent with the loose organization of the extracellular matrix in acute inflammatory reactions and its dense organization in the chronic reactions.

Animals↗

Two-dimensional electrophoresis in proteome expression analysis.

Cell proteomes are complex, given they consist of several thousand proteins. Two-dimensional electrophoresis (2DE) is unique not only for its ability to simultaneously separate thousands of proteins but also for detecting post- and co-translational modifications, which cannot be predicted from genome sequences. This review will describe the protocols applied to prepare 2D gels properly, and analyse and summarise the major challenges for successful proteome analysis using 2DE, i.e. the ability to analyse very alkaline, hydrophobic and/or low or high M(r) proteins with high resolution and the ability to detect minor components. Challenges involving sample preparation and solubilisation prior to the first dimension IEF/IPG step will be studied in depth. Sample preparation is crucial in 2DE studies and greatly influences other stages of the technique. It is the aim of this review not only to describe the challenges and limitations of 2DE but also to suggest the avenues, the evolution, the potential and the future of 2DE in proteomics.

Electrophoresis, Gel, Two-Dimensional↗

The focus and conduct of clinical trials.

This paper discusses some issues regarding how putative stop-smoking treatments should be evaluated. Preliminary evaluations of treatments have used withdrawal symptoms as a surrogate for abstinence in an attempt to decide those treatments on which to carry out expensive full-scale clinical trials. However, withdrawal symptom severity has not been shown to relate to long-term abstinence in any prospective studies. Until a better understanding of the relationship between withdrawal symptoms and abstinence is obtained withdrawal symptoms cannot be considered an appropriate surrogate for abstinence. Research is needed into what pattern of short-term abstinence provides the best predictor of long-term abstinence. Evidence from carbon monoxide validation of short-term abstinence raises doubts about whether minor lapses back to smoking are likely to lead to full blown relapse. Further research into the use of expired-air CO in validation of claims of abstinence is required. Finally, the traditional clinical trials format is not well suited to evaluation of treatment programmes with a large behavioural component. An alternative based on the principles underlying biological evolution is proposed.

Clinical Trials as Topic↗

DNA replication fidelity.

DNA replication fidelity is a key determinant of genome stability and is central to the evolution of species and to the origins of human diseases. Here we review our current understanding of replication fidelity, with emphasis on structural and biochemical studies of DNA polymerases that provide new insights into the importance of hydrogen bonding, base pair geometry, and substrate-induced conformational changes to fidelity. These studies also reveal polymerase interactions with the DNA minor groove at and upstream of the active site that influence nucleotide selectivity, the efficiency of exonucleolytic proofreading, and the rate of forming errors via strand misalignments. We highlight common features that are relevant to the fidelity of any DNA synthesis reaction, and consider why fidelity varies depending on the enzymes, the error, and the local sequence environment.

Base Pair Mismatch↗

Psychopathological assessment in children affected by Duchenne de Boulogne muscular dystrophy.

BACKGROUND: Several studies on the intelligence of children suffering from Duchenne muscular dystrophy (DMD) found impairments in linguistic functions, memory and affective development. Memory deficit mainly involves long-term memory; short-term memory impairment was also present, even if less frequently. Some studies tried to establish a correlation between the distal deletion of the dystrophin gene and low intelligence levels. METHODS: The present study investigated the cognitive, emotional and relational states in a group of DMD children. The patients were selected on the basis of physical examination, muscle biopsy, histochemical analysis, genetic testing, regular schooling. Molecular genetic testing detected a deletion in 2 high frequency deletion regions in all subjects. The following psychodiagnostic tests were used for assessment: WISC-R, Spontaneous Drawing, Draw-A-Person test, Family Drawing, Thematic Apperception test and Rorschach test. RESULTS: No impairment of the intellectual function was detected in the group of children we examined; only 2 subjects had a total IQ below average. Instead, psychic disorders were detected such as proneness to isolation, self-depreciation, past experiences of marginalization, minor depressive symptoms, insecurity signs, hypochondriac worries and high level of anxiety. In addition children exhibited poor adaptation to the environment and labile affectivity, scarcely controlled by the higher conscious levels. CONCLUSIONS: These disorders are often a dynamic prolongation of a psychological process starting when the diagnosis is made and continuing in a slow and latent fashion throughout the evolution of the disease.

Anxiety↗

[What is Helicobacter pylori?: associated diseases in human].

Helicobacter pylori (H. pylori) is a spiral gram-negative bacterium, characterized by positive urease, catalase and oxidase activity. The complete resolution of the full genome has elucidated the biological characteristics, the pathogenicity, and the bacterial evolution. The infection is acquired in childhood by oral-oral transmission in developed countries, probably an intra-familiar transmission. The infection has an association with chronic histological gastritis, peptic ulcer, gastric cancer and MALT lymphoma in the stomach. All patients with H. pylori infection have histological gastritis and most of them remain asymptomatic for life. Only a minority of the infected individuals occurs ulceration or gastric cancer. Cure of the infection prevents recurrence of peptic ulcer without persistent treatments against ulceration. Concerning gastric cancer, WHO concluded in 1994 that H. pylori is a definite carcinogen in humans on the basis of epidemiological studies. Evidences that the infection leads to the development of gastric cancer have been accumulated in animal models as well as in vitro experimental studies. Such clinical diversities are caused by variations of H. pylori pathogenicity, host susceptibility, environmental factors including foods and those interactions. At present, an eradication treatment of H. pylori, combined with a proton-pump inhibitor and two antibiotics (clarithromycin and amoxicillin) is restrictedly approved in the patients with gastric or duodenal ulcer by Japanese health care system.

Amoxicillin↗

The highly conserved N-terminal domains of histones H3 and H4 are required for normal cell cycle progression.

The N-terminal domains of the histones H3 and H4 are highly conserved throughout evolution. Mutant alleles deleted for these N-terminal domains were constructed in vitro and examined for function in vivo in Saccharomyces cerevisiae. Cells containing a single deletion allele of either histone H3 or histone H4 were viable. Deletion of the N-terminal domain of histone H4 caused cells to become sterile and temperature sensitive for growth. The normal cell cycle progression of these cells was also altered, as revealed by a major delay in progression through the G2 + M periods. Deletion of the N-terminal domain of histone H3 had only minor effects on mating and the temperature-sensitive growth of mutant cells. However, like the H4 mutant, the H3 mutants had a significant delay in completing the G2 + M periods of the division cycle. Double mutants containing N-terminal domain deletions of both histone H3 and histone H4 were inviable. The phenotypes of cells subject to this synthetic lethality suggest that the N-terminal domains are required for functions essential throughout the cell division cycle and provide genetic evidence that histones are randomly distributed during chromosome replication.

Alleles↗

Differential distribution of gonadotropin-releasing hormone-immunoreactive neurons in the stingray brain: functional and evolutionary considerations.

Gonadotropin-releasing hormone (GnRH) is a neuropeptide that occurs in multiple structural forms among vertebrate species. Bony fishes, amphibians, reptiles, birds, and mammals express different forms of GnRH in the forebrain and endocrine regions of the hypothalamus which regulate the release of reproductive gonadotropins from the pituitary. In contrast, previous studies on bony fishes and tetrapods have localized the chicken GnRH-II (cGnRH-II) nucleus in the midbrain tegmentum and, combined with cladistic analyses, indicate that cGnRH-II is the most conserved form throughout vertebrate evolution. However, in elasmobranch fishes, the neuroanatomical distribution of cGnRH-II and dogfish GnRH (dfGnRH) cells and their relative projections in the brain are unknown. We used high-performance liquid chromatography and radioimmunoassay to test for differential distributions of various GnRH forms in tissues from the terminal nerve (TN) ganglia, preoptic area, and midbrain of the Atlantic stingray, Dasyatis sabina. These experiments identified major peaks that coelute with cGnRH-II and dfGnRH, minor peaks that coelute with lamprey GnRH-III (lGnRH-III), and unknown forms. Immunocytochemistry experiments on brain sections show that dfGnRH-immunoreactive (-ir) cell bodies are localized in the TN ganglia, the caudal ventral telencephalon, and the preoptic area. Axons of these cells project to regions of the hypothalamus and pituitary, diencephalic centers of sensory and behavioral integration, and the midbrain. A large, discrete, bilateral column of cGnRH-II-ir neurons in the midbrain tegmentum has sparse axonal projections to the hypothalamus and regions of the pituitary but numerous projections to sensory processing centers in the, midbrain and hindbrain. Immunocytochemical and chromatographic data are consistent with the presence of lGnRH-III and other GnRH forms in the TN that differ from dfGnRH and cGnRH-II. This is the first study that shows differential distribution of cGnRH-II and dfGnRH in the elasmobranch brain and supports the hypothesis of divergent function of GnRH variants related to gonadotropin control and neuromodulation of sensory function.

Animals↗

Angioplasty and stenting of the cervical carotid bifurcation: report of a 4-year series.

Over a period of 46 months, 71 cervical carotid bifurcation stenotic lesions were treated by angioplasty and/or stenting. The stenosis was atherosclerotic in 61 cases, post-surgical or post-radiation in ten cases. The initial technical choice was that of primary stenting without cerebral protection; this attitude has been modified in recent cases by use of a protection balloon or filter. A technical success rate of 98% was achieved (71 cases treated out of 73 attempted). From the angiographic point of view, in all cases good restoration of the luminal diameter was obtained. There were three completely regressive minor strokes (4.2%), and one major stroke (1.4%). A follow-up of at least 1 year is available for 50 patients; a restenosis of less than 50% occurred in four (8%). In conclusion, angioplasty and stenting of the cervical carotid bifurcation is feasible in relatively safe conditions. However, analysis of the case complicated by a major stroke and the evolution of protection devices in recent years suggest the use of such devices for brain protection. The most suitable condition for endovascular treatment is considered to be an intermediate stenosis, i.e. with a residual lumen for safe passage of the devices used, without need for dangerous friction on plaque surfaces. The most dangerous phase of the treatment is dilation of the plaque by the balloon; deployment of an oversized stent without dilation is desirable whenever possible.

Aged↗