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PubMed2002

Monteplase reduces infarct volume and hemorrhagic transformation in rat model of embolic stroke.

Monteplase, a modified recombinant tissue plasminogen activator (rt-PA), has a long half-life and reduces binding to plasminogen activator inhibitor. In this study we investigated whether its systemic administration reduces infarct volume without increasing the risk of intra-cerebral hemorrhage. The effect of the drug was tested on an embolic stroke rat model that uses white clots. Thirty minutes after clot embolization, rats were infused with 2.2 mg kg(-1) of monteplase or the same amount of saline, over 60 min. Relative regional cerebral blood flow had recovered 60 min after monteplase administration and infarct volume was significantly smaller 24 h after clot embolization in the monteplase-treated rats (47.0 mm3) than in the saline-treated rats (130.4 mm3). Also, the hemorrhagic transformation area was significantly smaller in monteplase-treated rats (0.8 mm2 vs. 18.0 mm2, respectively). These results indicate monteplase can be a promising thrombolytic agent for treatment of the acute stage of cerebral ischemia.

Animals↗
PubMed2006

Estimation of postmortem interval from human pericardial fluid electrolytes concentrations in Chandigarh zone of India: log transformed linear regression model.

Estimation of postmortem interval from changes in postmortem pericardial fluid electrolytes concentration is the topic of discussion in the study. Querido [Querido D. Double logarithmic, linear relationship between plasma sodium/potassium concentration ratio and postmortem interval during the 6-96h postmortem period in rats. Forensic Sci Int 1990;44:125-34; Querido D. Linearization of the relationship between postmortem plasma chloride concentration and postmortem interval in rats. Forensic Sci Int 1990;45:117-27] and Singh et al. [Singh D, Prashad R, Parkash C, Bansal YS, Sharma SK, Pandey AN. Linearization of relationship between serum sodium, potassium concentration, their ratio and time since deaths in Chandigarh zone of north west India. Forensic Sci Int 2002;130:107; Singh D, Prashad R, Parkash C, Sharma SK, Pandey AN. Double logarithmic linear relationship between plasma chloride concentration and time since death in humans in Chandigarh zone of north west India. Legal Med 2003;5:49-54] had demonstrated a highly significant double logarithmic linear relationship between the time since death and the plasma sodium/potassium ratio as well as with plasma chloride concentration in Wistar rats and human, respectively. In view of these facts, the present study was carried out to substantiate this propensity in this transcellular extension of blood plasma. Electrolytes analysis in postmortem pericardial fluid obtained from 311 subjects revealed that correlation of time since deaths with potassium, sodium/potassium ratio and phosphorus was highly significant (p<0.001) during 2.5-58h of deaths. Not withstanding, time since death although modulated by ambient temperature could be predicted by log transformed multiple regression equation derived from the combination of potassium, chloride and phosphorus electrolytes concentration with standard error (SE) of prediction (in log hours) of 0.1840h and by double logarithmic model with SE (in log hours) of 0.1959, 0.2068 and 0.2088h from potassium, sodium/potassium ratio and phosphorus electrolytes, respectively.

Electrolytes↗
PubMed2004

Phase transformations in a model mesenchymal tissue.

Connective tissues, the most abundant tissue type of the mature mammalian body, consist of cells suspended in complex microenvironments known as extracellular matrices (ECMs). In the immature connective tissues (mesenchymes) encountered in developmental biology and tissue engineering applications, the ECMs contain varying amounts of randomly arranged fibers, and the physical state of the ECM changes as the fibers secreted by the cells undergo fibril and fiber assembly and organize into networks. In vitro composites consisting of assembling solutions of type I collagen, containing suspended polystyrene latex beads ( approximately 6 microm in diameter) with collagen-binding surface properties, provide a simplified model for certain physical aspects of developing mesenchymes. In particular, assembly-dependent topological (i.e., connectivity) transitions within the ECM could change a tissue from one in which cell-sized particles (e.g., latex beads or cells) are mechanically unlinked to one in which the particles are part of a mechanical continuum. Any particle-induced alterations in fiber organization would imply that cells could similarly establish physically distinct microdomains within tissues. Here we show that the presence of beads above a critical number density accelerates the sol-gel transition that takes place during the assembly of collagen into a globally interconnected network of fibers. The presence of this suprathreshold number of beads also dramatically changes the viscoelastic properties of the collagen matrix, but only when the initial concentration of soluble collagen is itself above a critical value. Our studies provide a starting point for the analysis of phase transformations of more complex biomaterials including developing and healing tissues as well as tissue substitutes containing living cells.

Animals↗
PubMedDate not supplied

[Aneuploid model of meiotic transformation mechanisms in wheat. 2. Prevention of homologue synapsis].

Two main elements of the mechanism of preventing the homoeologue synapsis were revealed using statistical analysis of the univalent behavior in meiotic anaphase I in the whole series of monosomic lines of wheat cultivar Milturum 553. One of the elements was found to be controlled by chromosomes 1B, 3B and 6A, and the latter being equally effective in both double and single doses.

Aneuploidy↗
PubMed2005

Notch1 mutations are important for leukemic transformation in murine models of precursor-T leukemia/lymphoma.

NOTCH1 is frequently mutated in human precursor T-cell lymphoblastic leukemia/lymphoma (pre-T LBL). In the current study, we found that 13 of 19 cell lines and 29 of 49 primary tumors from SCL/LMO1, OLIG2/LMO1, OLIG2, LMO1, NUP98/HOXD13, and p27(-/-)/SMAD3(+/-) mice had Notch1 mutations in either the heterodimerization (HD) or the glutamic acid/serine/threonine (PEST) domain but not both. Thymocytes from clinically healthy SCL/LMO1 mice aged 5 weeks did not have Notch1 mutations, whereas thymocytes from clinically healthy SCL/LMO1 mice aged 8 to 12 weeks did have Notch1 mutations and formed tumors upon transplantation into nude mice. Remarkably, all of the HD domain mutations that we identified were single-base substitutions, whereas all of the PEST domain mutations were insertions or deletions, half of which mapped to 1 of 2 mutational "hot spots." Taken together, these findings indicate that Notch1 mutations are very frequent events that are acquired relatively early in the process of leukemic transformation and are important for leukemic cell growth.

Age Factors↗
PubMed2002

Classifying the probability of urinary incontinence in psychogeriatric nursing home patients.

Urinary incontinence (UI) frequently occurs in psychogeriatric nursing home patients. In general the personnel involved in the care for these patients act on incontinence noted. Patients are not monitored or classified according to likelihood or severity of incontinence. This study was conducted to develop and validate a model for the classification of the likelihood of UI in demented nursing home patients. A multi-center cross-sectional study was conducted using data on clinical and functional status of 692 subjects. Subjects were subdivided in a Derivation set of 532 patients and a Validation set of 160 patients. The data were ascertained with questionnaires completed by physicians and nursing staff. All psychogeriatric wards (25) of four Dutch nursing homes were included. Using univariate logistic regression analysis on the derivation set we identified correlates of UI among 22 clinical and functional patient characteristics. Subsequently, we developed a classification model for prevalent UI, including independent patient characteristics by means of multivariable logistic regression. Next, we stratified patients into groups with varying likelihood's of UI based on the model developed. Subsequently, we transformed the model to an easy applicable classification rule for the identification of patient subgroups with high or low likelihood on UI. Finally, the rule was validated on the validation set. The independent multivariate factors associated with urinary incontinence were impaired ADL and mobility, diminished alertness and fecal impaction. After transforming the regression model to an easy classification rule, the scores ranged from 0 to 7. The area under the curve was 0.88 (95% Confidence Interval (CI): 0.85-0.91) in the derivation set. In the validation set a similar area under the curve was obtained (0.90 (95% CI: 0.85-0.95)). Among subjects with none of the associated factors the rule classified 0.5% as incontinent patients. In case all associated factors were present the proportion classified as incontinent increased to 91%. In conclusion, the developed classification rule provides means to stratifying nursing home patients according to their likelihood of being incontinent of urine.

Journal Article↗
PubMed1994

Nucleolar organizer regions as a marker of incipient transformation in a model of experimental carcinogenesis.

Nucleolar organizer regions stained selectively with a silver colloid technique (AgNOR) were evaluated during the process of tumour promotion in the skin of mice. Tumour promotion and control skin samples were processed for identification of AgNOR by light microscopy and submitted to a morphometric study of the following AgNOR-related variables: nuclear area (V.NUC); AgNOR number per nucleus (N.NOR); single AgNOR area (V.NOR); total AgNOR area per nucleus (TV.NOR) and proportion of nucleus occupied by AgNOR (TV.NOR/V.NUC). N.NOR exhibited significant differences between control and tumour tissue, but in the promotion period, N.NOR did not exhibit a significant rise until week 24. V.NOR and TV.NOR rose significantly as early as 2 weeks after the onset of promotion when the cells fail to exhibit unusual microscopic features. The significant increase in AgNOR material at the beginning of the promotion period reveals the potential value of the variables assessed in the early quantitative evaluation of cellular alterations which could be linked to the probability of tumour development. Rise in AgNOR material would indicate transcriptional activation leading to an increase in protein synthesis and, ultimately, to the expression of an altered phenotype.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1997

The vestibular system as a model of sensorimotor transformations. A combined in vivo and in vitro approach to study the cellular mechanisms of gaze and posture stabilization in mammals.

To understand the cellular mechanisms underlying behaviours in mammals, the respective contributions of the individual properties characterizing each neuron, as opposed to the properties emerging from the organization of these neurons in functional networks, have to be evaluated. This requires the use, in the same species, of various in vivo and in vitro experimental preparations. The present review is meant to illustrate how such a combined in vivo in vitro approach can be used to investigate the vestibular-related neuronal networks involved in gaze and posture stabilization, together with their plasticity, in the adult guinea-pig. Following first a general introduction on the vestibular system, the second section describes various in vivo experiments aimed at characterizing gaze and posture stabilization in that species. The third and fourth parts of the review deal with the combined in vivo-in vitro investigations undertaken to unravel the physiological and pharmacological properties of vestibulo-ocular and vestibulo-spinal networks, together with their functional implications. In particular, we have tried to use the central vestibular neurons as examples to illustrate how the preparation of isolated whole brain can be used to bridge the gap between the results obtained through in vitro, intracellular recordings on slices and those collected in vivo, in the behaving animal.

Animals↗
PubMed1990

Histocompatible miniature, boar model: selection of transformed cell lines of B and T lineages producing retrovirus.

A lymphoblastoid cell line (B1) was isolated in culture following a brief exposure to 5-azacytidine from peripheral-blood mononuclear cells of a boar previously injected with cells (Shimozuma) producing porcine retrovirus (Tsukuba-1) and suffering a severe non-neoplastic syndrome at autopsy. B1 cell line and 5 of its sublines were propagated for more than 100 generations, retaining doubling times comprised between 16.8 and 27.5 hr and growing readily in agarose or agar (plating efficiency: 5 to 50%). Karyotype analyses showed that 4 sublines were nearly diploid, except for cells of L14, which displayed a monosomy affecting chromosome 18 pair. Two sublines (L35 and L45) were considered as being of T-cell lineage, since MSA, antigen was observed on the surface of approximately 30% of cells. Three sublines (L23, L14 and L52) were considered of B-cell lineage, since membrane immunoglobulins were observed on the cell surface. In addition, sublines L23 and L52 were actively secreting immunoglobulin of mu isotype. Retrovirus particles were evidenced in gradient-purified preparation of 200-fold-concentrated cell culture supernatants of the B1 cell line, L14, L35 and L52 sublines, using both a reverse transcriptase activity assay and electron microscopic observation. These cell lines can be used to select for porcine retrovirus variants with transforming potential for lymphocytes of B and T lineages.

Animals↗
PubMed1977

The shape of workspace data transformation on a model basis.

Adapting the dimensional structure of a piece of equipment to the physical capabilities of an operator is a typical ergonomics problem. The author describes the trial of a model presentation of the movement abilities of an operator, and a condensed system of notation of spatial data.

Journal Article↗
PubMed1995

An illusory transformation in a model of optic flow processing.

We present results from computer simulations of a biologically plausible model of heading detection in the visual motion pathway of higher mammals. These simulations are closely related to a recently discovered visual illusion in optic flow processing in humans. The model reproduces the results described for humans and suggests a possible explanation, namely that humans interpret the illusory stimuli in terms of egomotion. It provides further indication that the visual system makes use of visual information to cope with eye movement effects in dealing with optic flow.

Algorithms↗
PubMed2005

Nomographic representation of logistic regression models: a case study using patient self-assessment data.

Logistic regression models are widely used in medicine, but difficult to apply without the aid of electronic devices. In this paper, we present a novel approach to represent logistic regression models as nomograms that can be evaluated by simple line drawings. As a case study, we show how data obtained from a questionnaire-based patient self-assessment study on the risks of developing melanoma can be used to first identify a subset of significant covariates, build a logistic regression model, and finally transform the model to a graphical format. The advantage of the nomogram is that it can easily be mass-produced, distributed and evaluated, while providing the same information as the logistic regression model it represents.

Algorithms↗
PubMed1997

Model SV40-transformed fibroblast lines for metabolic studies of human prosaposin and acid ceramidase deficiencies.

Skin fibroblasts from patients with Farber disease (acid ceramidase deficiency) and from two siblings of the only known family affected with prosaposin deficiency were transformed by transfection with a plasmid carrying the SV40 large T antigen. The prosaposin-deficient transformed cell lines conserved their original metabolic defects, and in particular they were free of detectable immunoreactivity when using anti-saposin B and anti-saposin C antisera. Ultrastructurally, the cells contained heterogeneous lysosomal storage products. As found for their parental cell lines, the SV40-transformed fibroblasts exhibited deficient in vitro activities of lysosomal ceramidase and beta-galactosylceramidase, but a normal activity of acid sphingomyelinase. As observed for SV40-transformed fibroblasts from Farber disease, degradation of radioactive glucosylceramide or low density lipoprotein-associated radiolabelled sphingomyelin by the prosaposin-deficient cells in situ showed a clear impairment in the turnover of lysosomal ceramide. Ceramide storage in prosaposin-deficient cells was also demonstrated by ceramide mass determination. In contrast to acid ceramidase deficient cells, both the accumulation of ceramide and the reduced in vitro activity of acid ceramidase in cells from prosaposin deficiency could be corrected by addition of purified saposin D. The data confirm that prosaposin is required for lysosomal ceramide degradation, but not for sphingomyelin turnover. The SV40-transformed fibroblasts will be useful for pathophysiological studies on human prosaposin deficiency.

Acid Ceramidase↗
PubMed2002

A general approach to transform a lake model for one radionuclide (radiocesium) to another (radiostrontium) and critical model tests using data for four Ural lakes contaminated by the fallout from the Kyshtym accident in 1957.

This paper presents results of a model test carried out within the framework of the COMETES project (EU). The aim of the work was to change the structure of the MOIRA lake model for radiocesium so that it can be applied more generally for, in principle, all types of radionuclides and heavy metals. This general lake model is used within the MOIRA decision support system (DSS; MOIRA and COMETES are acronyms for EU-projects). The model is based on a set of differential equations and a specific modelling structure. It incorporates all important fluxes to, from and within lakes in a general manner. Yet the model is driven by a minimum of variables accessible from standard maps and monitoring programs. The model can be separated into two parts, a general part with equations applicable for all types of water pollutants and a substance-specific part. This model has previously been validated for 137Cs from many lakes covering a wide domain and yielded excellent predictive power. The alterations discussed in this work are meant to be general and radiostrontium is used as a typical element. Radiostrontium is known to be more mobile than radiocesium and all abiotic parts of the model handling fixation and mobility have been altered. The new model for 90Sr has been critically tested using data from four lakes heavily contaminated with 90Sr from the Kyshtym accident in the Southern Urals, Russia, using empirical data from a period from 1958 to 1995 for 90Sr in fish (here goldfish), water and sediments.

Cesium Radioisotopes↗
PubMed2003

The transformation of the model organism: a decade of developmental genetics.

The past decade has seen the development of powerful techniques to dissect the molecular processes that regulate development. New tools have been used to reveal the basis of cell polarity, morphogen gradients and regulation of signaling in developing animals. Cell biology and developmental biology have become closely intertwined, and many genes that had been thought of as regulators of general cell biological (housekeeping) functions have been shown to act as specific developmental regulators. Vertebrate developmental genetics is now flourishing, with forward and reverse genetics in both zebrafish and the mouse providing new dimensions to our understanding of development.

Animals↗