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Biomedical subjects

T Simon

Publications and source records attributed to T Simon.

At least 19 recordsLinked to original sources
PubMed1992

Physiological growth of arteries in the rat heart parallels the growth of capillaries, but not of myocytes.

Maladaption to hemodynamic overload, especially to arterial hypertension, has important clinical implications, and it is necessary to obtain criteria in order to discriminate physiological and pathological growth processes. We investigated the physiological growth of intramyocardial arteries in the rat heart. A new stereological method was introduced to determine the length of intramyocardial arteries from counts on histological sections. Four groups of male Sprague-Dawley rats of different ages were investigated. The growth rate of arteries was characterized by the growth coefficient b according to the exponential function y = axb (allometric growth function). Analysis of left ventricular weights (LVW) and total lengths of left ventricular intramyocardial arteries (L) revealed Lv = constant.LVW0.71 (r = 0.77, P < 0.001). The growth coefficient b < 1 indicates that the arterial supply of the heart, i.e. the length density of arteries Lv (length per unit myocardial volume), decreases during normal growth. Empirically, we found L = constant.LVW-0.28 (r = 0.43, P < 0.01). Previously, we estimated growth rates of b = 0.33 for the total length of left ventricular myocytes and b = 0.71 for the total length of capillaries. Thus, growth of intramyocardial arteries considerably exceeds the length increase of myocytes, but is proportional to the length increase of capillaries. Growth analysis of total mitochondrial volume using historical data of our group revealed proportionality to arteries, as well (b = 0.76). This indicates that growth of arteries and capillaries may be determined by oxygen consumption.

Animals↗
PubMed1992

Hydrated clearance of gadolinium-DTPA as a measurement of glomerular filtration rate.

Technetium (99mTc)-diethylene triamine pentaacetic acid (DTPA) hydrated clearance studies are accurate for determining GFR but require special facilities for handling and measuring samples. We investigated the potential of a non-radioactive paramagnetic analog, Gadolinium (Gd)-diethylene triamine pentaacetic acid (DTPA), an approved NMR contrast agent, as a glomerular filtration marker. Instead of relying on the radioactivity of technetium, this test is based on the fact that gadolinium induces alterations in the NMR T1 relaxation times in blood and urine samples. Ninety patients underwent simultaneous determinations of GFR using 1 mCi of Tc-DTPA and 0.05 mmol/kg Gd-DTPA (Berlex Labs) IV. The patients were hydrated with oral and intravenous fluid. Following a one hour equilibrium period, three or four consecutive urine collections were obtained; plasma samples were acquired at the beginning and end of each approximately 20-minute interval. 99mTc-DTPA radioactivity was determined with a scintillation counter. T1 relaxation times were measured on a 10 MHz NMR spectrometer. These were converted to Gd-DTPA concentration by comparison with standard solutions. The Gd-DTPA derived GFR closely approximated the 99mTc-DTPA derived GFR which ranged from 15 to 147 ml/min. The equation and correlation coefficient of the regression line is y = 1.04 x -2.2, r = 0.94. Thus, Gd-DTPA is a safe, non-radioactive indicator of GFR that may provide an alternative renal clearance method for clinical studies of progressive renal disease and nephrotoxicity.

Contrast Media↗
PubMed1992

Storage and transfusion of platelets collected by an automated two-stage apheresis procedure.

Platelets collected by using a two-stage automated blood cell separator were evaluated after 5 days of storage. The procedure caused no unanticipated physiologic changes in donors and produced greater than 3 x 10(11) intact platelets in 200 mL of plasma, plus an additional 400 mL of plasma with intact coagulation factors. Posttransfusion recovery of autologous radiolabeled platelets was comparable to that seen in platelets prepared by manual centrifugation techniques. Corrected count increments in 14 patients showed results similar to those with control transfusions. This device, which involves a collection time of less than 90 minutes, provides an option for platelet-pheresis in a variety of settings including blood mobiles.

Adult↗
PubMed1992

Synergistic interaction of interferon-beta and interferon-gamma in coxsackievirus B3-infected carrier cultures of human myocardial fibroblasts.

The antiviral effects of human interferon-beta (IFN-beta) and human recombinant interferon-gamma (rIFN-gamma) were studied in persistently coxsackievirus B3-infected carrier cultures of human myocardial fibroblasts over a period of 21 days. Synergism was observed with concentrations as low as 30 IU of IFN-beta plus 10 IU of rIFN-gamma/mL, reducing mean viral titers from 6.0 x 10(7) to 1.3 x 10(4) pfu/mL and number of infected cells from 14.4% to 0.1% as determined by quantitative in situ hybridization. Higher concentrations of IFNs (both > or = 30 IU/mL) were associated with transient antagonism followed by antiviral synergism. With 100 IU of IFN-beta plus 30 IU of rIFN-gamma/mL, elimination of infectious virus was consistently achieved and sustained for 6 weeks after cessation of IFN application, whereas at least threefold higher concentrations were required with single drugs. In summary, our data support a concept of low-dose IFN combination schedules that might become useful in the treatment of enteroviral heart disease.

Cells, Cultured↗
PubMed1992

A functional antibody mutant with an insertion in the framework region 3 loop of the VH domain: implications for antibody engineering.

We have studied the effects of a four residue insertion into the FR3 loop of the heavy chain variable region from the anti-NP antibody B1-8. The insertion mutant is obtained as secreted antibody without major defects in biosynthesis, indicating that antibody variable domains can accommodate length variation not only in complementarity determining regions (CDRs), but also in framework region (FR) loops. The B1-8 antigen binding site is not affected by the change in a neighbouring loop. FR3 insertions represent a new method of antibody engineering with a potential to obtain strong antigen binding by designing additional antigen contacting residues.

Amino Acid Sequence↗
PubMed1992

Polymorphism of dextromethorphan metabolism: relationships between phenotype, genotype and response to the administration of encainide in humans.

The polymorphism of dextromethorphan and encainide metabolism is genetically determined and is related to the activity of hepatic CYP2D6. In order to examine the relations between CYP2D6 phenotype, genotype and the electrocardiographic response to the oral administration of encainide, 110 healthy subjects were studied. Metabolic ratios were calculated in urine after oral administration of 40 mg of dextromethorphan and in plasma obtained 2.5 h after oral administration of 50 mg of encainide. Encainide-induced electrocardiographic changes were measured 2.5 h after oral administration of the drug. Genotype was determined in 52 subjects. Results showed that phenotype, either extensive or poor metabolizer, for CYP2D6-dependent metabolism could be identified from the dextromethorphan metabolic ratio calculated in urine, from the encainide metabolic ratio calculated in plasma and from the genotype. However, despite the fact that the changes in atrioventricular (PR) and intraventricular (QRS) conduction times produced by encainide were different in extensive and poor metabolizer subjects and correlated with CYP2D6 activity, the electrocardiographic response was never 100% specific and sensitive for the identification of either phenotype. Moreover, genotypic identification of heterozygous and homozygous extensive metabolizer subjects did not predict CYP2D6 activity, as determined by dextromethorphan and encainide metabolic ratios, or encainide response, as determined by intraventricular and atrioventricular changes. Thus, CYP2D6 activity does not fully predict the electrocardiographic effects of encainide, and genotype, as determined in our study, cannot replace the determination of metabolic ratio in predicting CYP2D6 activity and encainide response in extensive metabolizer subjects.

Adult↗
PubMed1992

[Establishment of reference values for fructosamine and HbA1c in childhood].

Reference values for fructosamine and glycated haemoglobin in children are still lacking. Using samples from 522 children (age range 1 day to 9 years), plasma electrophoresis was performed, fructosamine and total protein were determined in EDTA-plasma, and glucose and the fraction of glycated haemoglobin (HbA1c) were determined in EDTA blood. The results were grouped according to age (1, 3 and 5 days, 6-28 days, 2-12 months, 2-3 years, 4-6 years, and 7-9 years). Differences between the age groups were determined using the Mann-Whitney-U-test, and the values in each group were summarized where possible. The 95%-interval was calculated for fructosamine, protein-corrected fructosamine, and HbA1c.

Child↗
PubMed1991

[Changes in the knowledge and attitude of physicians and health professionals in relation to AIDS during 1988-1990].

The authors interviewed in 1988, 570 and in 1990 425 health personnel about their knowledge and attitudes with AIDS. The results of 1990 survey shows: 63-76% of subjects changed their working habits, the increase rate to 1988 data is 30-40% and 11.7-18.0% changed their habits in their private life, the rate of increasing are: 8-9%. The safety gloves was mentioned by 82.1%-20% more than in 1988. 14% of the interviewed doctors and other health workers are refuse the care of an AIDS or a HIV positive patient, this rate is the double than was in 1988. Among the information resources the rate of postgraduate education was by 10% lower and 95% of the interviewed persons nominated the mass media as a main information channel in their knowledges about AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Expression of 1,25-dihydroxyvitamin D3 receptors in normal and psoriatic skin.

Increasing evidence suggests an immunoregulatory function of the potent steroid hormone 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) which has been successfully applied for treatment of psoriasis. The skin is both a site of production and a target of 1,25(OH)2D3. In vitro, 1,25(OH)2D3 inhibits proliferation and stimulates differentiation of keratinocytes. We investigated the in situ expression of vitamin D-receptors (VDR) in normal and psoriatic skin by immunochemical methods. The VDR were visualized using the monoclonal antibody (MoAb) 9A7g to the VDR and the labeled avidinbiotin technique. Immunoreactivity was consistently confined to nuclei in all skin biopsies. In normal skin specimens (n = 10) VDR antigens were expressed in keratinocytes of all epidermal layers (except those of the stratum corneum) and in cells of the epidermal appendages. Double labeling experiments with MoAb to cluster-defined antigens indicated that melanocytes and approximately 75% of Langerhans cells exhibit 1,25(OH)2D3 receptors in normal skin biopsies (n = 5). Depending on their localization in skin compartments 42-62% of CD11b+ positive macrophages and 45-75% of CD3+ T lymphocytes expressed VDR. Non-lesional psoriatic skin specimens (n = 8) revealed nearly identical staining patterns. Lesional psoriatic skin specimens (n = 8) exhibited a significant increase of VDR expression both in basal and suprabasal epidermal layers as measured by computer-assisted morphometry and showed a remarkable change of the immune cell pattern: the densitity and proportion of VDR positive T lymphocytes and macrophages were higher in the epidermal and the perivascular papillary loop compartment. These in vivo findings strongly support the hypothesis that 1,25(OH)2D3 modulates immune response and cell proliferation/differentiation in human skin.

Adult↗
PubMed1990

Antibody domain mutants demonstrate autonomy of the antigen binding site.

We have constructed derivatives of a lambda I light chain-bearing anti-(4-hydroxy,3-nitrophenyl)acetyl (NP) antibody which have the V regions exchanged between heavy chains and light chains of the kappa or lambda I type. These antibodies are assembled and secreted normally, and bind haptenic and macromolecular ligands like the wild-type; similar results are obtained for monovalent heterodimers of VHCL and lambda I light chains. The observed independence of the binding site from the constant region context argues against a role of longitudinal interactions between constant and variable domains in antigen recognition, and therefore against cooperativity between binding sites.

Animals↗
PubMed1990

[New methods for the morphometric analysis of anisotropic tissues].

Some unbiased, design-based stereological methods that have recently been developed for the study of anisotropic tissues like muscle, myocardium, brain, cartilage, and skin, are briefly reviewed. Vertical sections permit the unbiased estimation of surface density and mean volume-weighted particle volume from microscopic sections. The available experience includes various studies on malignant melanomas. In addition, the surface area of total organs (e.g., the pleural surface area) can be determined with vertical sections, which was hitherto not feasible. The orientator is a simple method to generate isotropic sections in biological material. With the orientator method it is possible to determine not only the surface density, but also the length density of the objects. Thus the method is suitable for the study of fascicular systems (tubules etc.), and for the study of vascularisation in particular.

Animals↗
PubMed1989

Anti-inflammatory drugs in experimental atherosclerosis. 7. Spontaneous atherosclerosis in WHHL rabbits and inhibition by cortisone acetate.

The Watanabe heritable hyperlipidemic (WHHL) rabbit, an animal model for familial hypercholesterolemia, has a deficiency in low density lipoprotein (LDL) receptor binding and exhibits elevated plasma lipoprotein levels and spontaneous atherosclerosis. Since atherosclerotic plaque formation has a number of features in common with the inflammatory process, we have investigated the effect of dietary supplementation with an anti-inflammatory steroid (cortisone acetate, 5 mg daily for 3 months) on atherosclerosis using the WHHL rabbit as a model. Atherosclerotic plaque formation in cortisone-fed animals was reduced by about 60% compared to control WHHL rabbits. Steroid administration increased circulating cholesterol levels modestly and triglycerides were increased about 6-fold. While very low density lipoprotein (VLDL)-cholesterol was increased, LDL-cholesterol levels were decreased and the particle was more triglyceride-enriched as well as less dense. Steroid-fed animals also exhibited decreased platelet aggregation and increased aortic 15-lipoxygenase activity. The histological observations showed typical fibrous plaques in aortas of both control and cortisone-fed rabbits, with intima thickened by foamy macrophages and subcellular lipoproteinaceous debris covered by a fibrous cap. These findings thus indicate that steroids reduce the rate of plaque initiation or progression but do not significantly change the histological appearance of the lesion.

Animals↗
PubMed1988

Hydroxyurea and etoposide: in vitro synergy and phase I clinical trial.

L1210 murine leukemia cells were treated with hydroxyurea (10-200 microM) for 24 hours and/or etoposide (0.17-3.4 microM) for 2 hours. Combination treatments used a fixed molar hydroxyurea:etoposide ratio of 58.9:1, and drug-drug interactions were quantitated according to the median effect principle. Hydroxyurea and etoposide were antagonistic at low doses at which the survival fraction was greater than 0.5 and synergistic at higher doses at which the survival fraction was less than 0.25. In a phase I clinical trial, 19 patients were treated with the two drugs at one of three dose levels. The dose-limiting toxic effect was myelosuppression. Doses of 100 mg of etoposide/m2 per day by continuous infusion and 500 mg of hydroxyurea orally every 4 hours, both for 3 days, are recommended for phase II trials.

Adult↗