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At least 523 records · Page 29Linked to original sources
PubMed1972

Metabolism of adrenal cholesterol in man. I. In vivo studies.

The kinetics of plasma and adrenal cholesteral equilibration were analyzed in patients undergoing bilateral adrenalectomy for generalized mammary carcinoma. A biological model is proposed to help in the understanding of adrenal cholesterol physiology. It comprises two intracellular compartments: (1) A compartment of free adrenal cholesterol which is small (of the order of 17 mg) but turns over very fast; it is renewed approximately 8 times per day: 3 times by the inflow of free plasma cholesterol, and 5 times by the hydrolysis of esterified adrenal cholesterol, the contribution of adrenal cholesterol synthesis appearing to be relatively small. (2) A compartment of esterified adrenal cholesterol which is 20 times larger; it is constantly renewed by in situ esterification and hydrolysis with a daily fractional turnover rate of the order of 0.25. The direct and selective accumulation of plasma cholesteryl esters is practically absent. Only free adrenal cholesterol returns to plasma, mostly after conversion into steroid "hormones."However small the synthesis of adrenal cholesterol may be, it seems more important in the zona "reticularis." On the other hand, the inflow of plasma cholesterol and the turnover of the free adrenal compartment tend to be faster in the zona "fasciculata." The equilibration of plasma and adrenal cholesterol can proceed unmodified under conditions of ACTH suppression. In one patient with Cushing's disease the size of the two adrenal compartments was clearly increased but their equilibration with plasma cholesterol proceeded normally. In another patient the kinetics of hydrocortisone corresponded to those of free adrenal cholesterol in the control studies.

Adrenal Glands↗
PubMed1994

Local control versus dose or overall time: from coefficients to percentages.

When clinical results are analysed to find the treatment variables which affect the outcome, two types of multivariate analysis are done. Firstly, a determination of which variables are important is made: from age, gender, stage, histology, total dose, overall time, etc. Secondly, a quasi-biological model may be set up which includes those variables, e.g. Function (p) = Variable 1 + Variable 2 + ... + alpha x dose + beta x dose x (dose per fraction) - gamma x (overall time) where p is the probability of local control and "Function" is a logit or double-log function. The coefficients thus determined are often presented simply in raw form, or as ratios such as alpha/beta or gamma/alpha where any conversion factors from "Function (p)" to percentages are assumed conveniently to cancel out. However, it is mathematically possible to convert each coefficient directly into "percent change in local control per unit dose" (for alpha), or "percent per unit time" (for gamma), without recourse to the obvious convenience of the ratios. These converted values are more understandable than the coefficients themselves. They mean the rate of change of local control with (for example) total dose if overall time and dose per fraction were held constant; or rate of loss of local control with prolongation if total dose and dose per fraction were held constant. Even though heterogeneity may alter these slopes considerably from the theoretically maximum Poisson slopes, they still tell us what is happening averaged over the group of patients being studied, with often interesting insights.

Dose-Response Relationship, Radiation↗
PubMed2004

Physical properties of Escherichia coli P pili measured by optical tweezers.

The mechanical behavior of individual P pili of uropathogenic Escherichia coli has been investigated using optical tweezers. P pili, whose main part constitutes the PapA rod, composed of approximately 10(3) PapA subunits in a helical arrangement, are distributed over the bacterial surface and mediate adhesion to host cells. They are particularly important in the pathogenesis of E. coli colonizing the upper urinary tract and kidneys. A biological model system has been established for in situ measurements of the forces that occur during mechanical stretching of pili. A mathematical model of the force-versus-elongation behavior of an individual pilus has been developed. Three elongation regions of pili were identified. In region I, P pili stretch elastically, up to a relative elongation of 16 +/- 3%. The product of elasticity modulus and area of a P pilus, EA, was assessed to 154 +/- 20 pN (n=6). In region II, the quaternary structure of the PapA rod unfolds under a constant force of 27 +/- 2 pN (n approximately 100) by a sequential breaking of the interactions between adjacent layers of PapA subunits. This unfolding can elongate the pilus up to 7 +/- 2 times. In region III, pili elongate in a nonlinear manner as a result of stretching until the bond ruptures.

Bacterial Adhesion↗
PubMed2001

An overview of the posters presented at Watermatex 2000. III: Model selection and calibration/optimal experimental design.

This paper presents an overview of the posters presented in sessions 7 and 8 of the Watermatex 2000 conference. These posters present two aspects of modelling biological processes--model selection and calibration. Special attention is given to the papers on OED (Optimal Experimental Design), which is a method of optimising the data collection for model selection and calibration. The presence of these presentations at the conference highlights the continuing significance of modelling and stresses the requirement of improvements in modelling techniques. The papers provide some contribution to this end.

Calibration↗
PubMed2001

[Current state and prospects for gene therapy of Duchenne muscular dystrophy in the world and in Russia].

Failure of drug therapy of Duchenne muscular dystrophy (DMD) stimulated intense search for adequate methods of gene therapy (GT) which would ensure effective delivery of the dystrophin (D) gene, its long-term persistence in transfected cells, and its expression in muscle fibers. The main results of the experimental GT of DMD with the use of viral and nonviral delivery of the D gene into muscles of biological models are discussed. Delivery of a mini-gene of D with a specific muscle promoter using a modified adenoassociated virus is currently the most promising method, which will soon be available for clinical trials. The main results of the studies on the DMD GT in Russia are summarized. The results of experiments on genetic transfection of mdx mice with marker genes and various constructions with the D gene are outlined. The genes are delivered into muscles by means of gene gun, electroporation, viral oligopeptides, liposomes, microspheres, lactoferine, and other nonviral vehicles. It is emphasized that consolidation of funds and efforts of all Russian laboratories dealing with gene and cell therapy of DMD are necessary to complete the experiments and start clinical trials.

Animals↗
PubMedDate not supplied

[Role of bacterial protease degrading secretory immunoglobulin A in Klebsiella persistence].

During the study of 186 K. pneumoniae clinical strains the presence of SIgA-protease activity was detected in 109 isolates (58.6%). The PCR test system permitting the detection of iga gene DNA in K. pneumoniae strains isolated in purulent inflammatory processes of different localization was developed. For the first time a conjugative plasmid with a mol. wt. of 100 MD was detected in K. pneumoniae clinical isolates. This plasmid controlled the capacity of inactivating SIgA, carried the markers of antibiotic resistance and was capable of expression in a wide circle of hosts belonging to the family Enterobacteriaceae. The results of in vitro experiments revealed that the strains containing plasmid SIgA were cytotoxic with respect to cells HEp-2 and more resistant to the digestive action of enzymes produced by the phagolysosomes of guinea pig peritoneal cells. As shown on the in vivo biological model with the use of the genetically linked pair of Salmonella typhimurium 274 vaccine strains, differing in SIgA-protease activity, plasmid pSigA ensured more prolonged survival of bacteria in mice in comparison with the nonplasmid variant. The study of SIgA-protease activity of K. pneumoniae strains circulating among patients with a view to the detection of clones causing the development of persistent infection was shown to have good prospects.

Animals↗
PubMed1992

[Teratology and epidemiology in the study of environmental teratogens].

The processes of cellular migration, cellular differentiation and cellular multiplication are studied, since these are the basic developmental processes upon which teratogenic agents act resulting in congenital malformations. We also carefully analyze the interactions between teratogen-embryo in order to establish adequate parameters for analysis of environmental teratogens, as well as experimental teratogenesis and epidemiology. Information on the pathogenesis of congenital malformations obtained from experimental teratology in an adequate biological model, can be extrapolated to the human. The etiology of congenital malformations resulting from environmental teratogens can only be elucidated through epidemiology, since there is species specificity. Such a study must fulfill the following prerequisites: diagnosis of the congenital malformation, ruling out genetic factors in the family tree and determination of the exact time of exposure to the possible teratogen during the pregnancy.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

[Causality in medicine].

The concept of causality is a part of every day life because man has always searched for the why of things as a way of dealing with and adapting to the world. In medicine, one of the central aims of study is identification of the factors or agents that cause disease with the intention of establishing treatments and especially, to apply preventive strategies. In this work, we conducted a brief review of the philosophical positions on causality, its biological models, as well as the tools used in clinical epidemiology to evaluate causal associations.

Causality↗
PubMed2005

Historical blunders: how toxicology got the dose-response relationship half right.

Substantial evidence indicates that reliable examples of hormetic dose responses in the toxicological literature are common and generalizable across biological model, endpoint measured and chemical class. Further evaluation revealed that the hormetic dose response model is more common than the threshold dose response model in objective, head-to-head comparisons. Nonetheless, the field of toxicology made a profound error by rejecting the use of the hormetic dose response model in its teaching, research, risk assessment and regulatory activities over nearly the past century. This paper argues that the hormetic dose response model (formerly called the Arndt-Schulz Law) was rejected principally because of its close historical association with the medical practice of homeopathy as a result of the prolonged and bitter feud between traditional medicine and homeopathy. Opponents of the concept of hormesis, making use of strong appeals to authority, were successful in their misrepresentation of the scientific foundations of hormesis and in their unfair association of it with segments of the homeopathic movement with extreme and discreditable views. These misrepresentations became established and integrated within the pharmacology and toxicology communities as a result of their origins in and continuities with traditional medicine and subsequently profoundly impacted a broad range of governmental risk assessment activities further consolidating the rejection of hormesis. This error of judgment was reinforced by toxicological hazard assessment methods using only high and few doses that were unable to assess hormetic responses, statistical modeling processes that were constrained to deny the possibility of hormetic dose response relationships and by the modest nature of the hormetic stimulatory response itself, which required more rigorous study designs to evaluate possible hormetic responses.

Animals↗
PubMed1990

[Use of the mother-fetus-newborn infant system for the study of combined effects of pesticides and other chemicals].

It is possible to state on the basis of the studies carried out that the system mother-fetus-new-born may be used as the most sensitive biological model to study separate, complex and combined exposure of mammals to chemicals. It was found out that the above mentioned system is highly sensitive and makes it possible to detect a damaging effect to chemicals even on the level of standardized values, while such doses do not produce any negative influence on the adult organism. The proposed system makes it possible to assess material and functional cumulation of chemical substances in the organism of mammals.

Animals↗
PubMed1990

Development of the vertebrate small intestine and mechanisms of cell differentiation.

The intestinal epithelium represents an attractive biological model of differentiation from stem cells to highly differentiated epithelial cells, not only during particular developmental events depending upon the vertebrate species considered but also throughout adult life. The ontogenic maturation of the intestinal epithelium arises from both a programmed expression of specific genes and epigenetic influences mainly due to epithelial and mesenchymal interactions and hormonal participation. In the present paper we review the structural and functional changes that occur in the amphibian, avian and mammalian intestine during embryonic and/or post-embryonic development. Furthermore, we review the data concerning the mechanisms which control the cytodifferentiation of the intestinal epithelium.

Animals↗
PubMed1990

Acute effects of carbon monoxide on cardiac electrical stability.

The objective of this project was to determine the effects of acute carbon monoxide exposure on cardiac electrical stability. To obtain a comprehensive assessment, diverse biological models were employed. These involved cardiac electrical testing in the normal and ischemic heart in anesthetized and conscious dogs. The experimental plan was designed both to examine the direct effects of carbon monoxide exposure on the myocardium and to evaluate possible indirect influences through alterations in platelet aggregability or changes in central nervous system activity in the conscious animal. Our results indicate that exposure to relatively high levels of carbon monoxide, leading to carboxyhemoglobin concentrations of up to 20 percent, is without significant effect on ventricular electrical stability. This appears to be the case in the acutely ischemic heart as well as in the normal heart. It is important to note that the total exposure period was in the range of 90 to 124 minutes. The possibility that longer periods of exposure or exacerbation from nicotine in cigarette smoke could have a deleterious effect cannot be excluded. We also examined whether or not alterations in platelet aggregability due to carbon monoxide exposure could be a predisposing factor for cardiac arrhythmias. A model involving partial coronary artery stenosis was used to simulate the conditions under which platelet plugs could lead to myocardial ischemia and life-threatening arrhythmias. We found no changes either in the cycle frequency of coronary blood flow oscillations or in platelet aggregability during carbon monoxide exposure. Thus, carbon monoxide exposure does not appear to alter platelet aggregability or its effect on coronary blood flow during stenosis. In the final series of experiments, we examined the effects of carbon monoxide exposure in the conscious state. The rationale was to take into consideration possible adverse consequences mediated by the central nervous system. We found no adverse effects on cardiac excitable properties in response to either a 2-hour or 24-hour-exposure paradigm. This appears to argue against major deleterious influences of carbon monoxide exposure as a result of direct myocardial actions or indirect actions mediated through effects on central nervous system activity.

Animals↗
PubMed1989

Determination of antigen concentration in tissue sections by immunodensitometry.

Our aim was to determine whether density of immunolabeling can be used to estimate the amount of an antigen in a tissue. The biological model was the pancreatic insulin-containing B cell. The insulin content of the pancreas of Wistar rats was decreased by five injections of glibenclamide (0.5, 1, or 2 mg/kg) every 12 hours. After resection of the whole pancreas specimens were taken for insulin extraction and measurement by radioimmunoassay and for immunocytochemistry. The sections were treated either by a polyclonal anti-insulin serum at 1/500 or 1/3000 and peroxidase-antiperoxidase complex or by a monoclonal anti-insulin serum at 1/500 and indirect immunoperoxidase. Peroxidase was revealed by diaminobenzidine. The density of immunostained B cells was determined with an automatic image analyzer (Ibas 2000, Kontron, FRG). Compared with controls, pancreatic insulin concentration was decreased by about 40, 60, and 85% in rats treated by the three doses of glibenclamide. A strong correlation was found between the insulin concentration and the optical density of islets under certain conditions: with the monoclonal anti-insulin serum (r = 0.90) and with the polyclonal anti-insulin serum at a high dilution (r = 0.95) but not at a low dilution (r = 0.13). With the latter, the optical density was high even in islets with reduced insulin content. In conclusion, a low dilution of antiserum should be used to detect cells with a small amount of antigen, whereas a higher dilution makes it possible to estimate the antigen concentration in the tissue. Thus, under appropriate conditions, a linear relationship exists between the optical density of the immunostained material and the concentration of immunoassayable antigen. This technique may thus prove useful in evaluating the functional state of cells, in particular secretory cells, under normal or pathological conditions.

Animals↗
PubMed1989

Toward a new approach in tumor cell heterogeneity studies using the concept of order.

A new methodology was developed to study dynamic processes topographically in biological systems by means of a graph-theoretical method. It is based upon order parameters obtained from a minimal spanning tree analysis coupled with computer simulations. The method was used to analyse the heterogeneous behavior of two neoplastic cell lines after treatment with laminin. The laminin-induced cell detachment was quantitated and shown to be inversely related to cell population density and thus to cellular interactions. Our statistical analysis is a very powerful tool to obtain information from seemingly disorderly heterogeneous biological models.

Animals↗
PubMed1989

[A tetrapolar circuit method using magnetic field for biological resistivity measurement].

A local impedance and its change were measured using a tetrapolar circuit combined with magnetic eddy current generator. By this method, current distribution can be restricted to a desired part, so as to eliminate errors due to uncertainty of the resistance between the electrode and the skin. The resistivity of a substance in a biological model measured by this method was nearly equal to that of the substance separated from the model. Sensitivity and localization were assessed in the other model composed of a piece of metal plate in a saline pool. The detection sensitivity was validated theoretically. The localization of the impedance pulsatile waveforms, measured at the proximal part of the forearm, was consistent with that of the arteries at this part. These results suggest that this method using eddy current should expand the application area of bio-impedance measurements.

Electric Conductivity↗
PubMed1986

Multicompartmental analysis of the kinetics of radioiodinated monoclonal antibody in patients with cancer.

A conceptual biologic model was developed and used to analyze the behavior of 123I-Lym-1 monoclonal antibody against African human B cell lymphoma in patients with B cell lymphoma. Originally, the observed data could not be simulated with parameters for homologous immunoglobulins reported in the literature because of a major processor that was capable of distinguishing this murine immunoglobulin from the patient's own immunoglobulins. With a nonlinear parametric model, the data observed in patients could be fitted to the model. The nonlinear parameter determined the transfer of antibody from the intravascular to a processor compartment, primarily the liver. This transfer was a function of the number of free receptors in the processor. Model simulated curves for the time course of concentration of antibody in the blood for different amounts of injected antibody revealed that blood clearance of radiolabeled antibody was profoundly decreased by increased amount of injected antibody. This model provides an explanation for the observations that tumor imaging is improved with injection of larger amounts of antibody, and a basis for modifying the pharmacokinetic behavior of an antibody in order to optimize radioimmunodiagnosis and radioimmunotherapy.

Antibodies, Monoclonal↗
PubMedDate not supplied

[Age-dependent gene induction in the quail oviduct. VIII. A survey of experimental data].

1974 we introduced the biological model of the progesterone-caused avidin biosynthesis in the quail oviduct for studies in the field of molecular gerontology. Using this model it is possible to determine quantitatively the biochemical events of the age-dependent reduction of the progesterone-caused gene-induction. In a series of experiments it was found that the main parameters of the age dependent reduction might be found on the level of transcription and post-transcription. Therefore the enzymic processes involved in the transcription of genetic information from the DNA to the heterogenous nuclear RNA as well as those processing this RNA species to mRNA are studied. During the progress in this field we could isolate and purify some enzymes (poly[A] nucleases) which are involved in the age-dependent "maturation" of mRNA. On the basis of the interrelation between the poly(A)-binding proteins and the specific poly(A) nucleases, an explanation of the age-dependent reduction of the progesteron-caused mRNA synthesis seems to be possible.

Aging↗