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Biomedical subjects

J Paul

Publications and source records attributed to J Paul.

At least 181 records · Page 10Linked to original sources
PubMed1990

Calcium entry blockade prevents leakage of macromolecules induced by ischemia-reperfusion in skeletal muscle.

Calcium kinetics and its intracellular mobilization are important in all biological processes. We used verapamil to examine the effect of calcium entry blockade on microvascular transport of macromolecules in ischemia-reperfusion injury. The rat cremaster muscle was splayed, placed in a Lucite intravital chamber, and suffused with bicarbonate buffer. The clearance of fluorescein isothiocyanate-conjugated dextran (FITC-dextran 150) was measured as an index of microvascular transport. After determination of baseline data (clearance of FITC-dextran 150, 3.0 +/- 0.5 microliters/5 min/g), the muscle was made ischemic for 2 hours by clamping its vascular pedicle and subsequently was reperfused for 2 hours. Ischemia-reperfusion produced a marked increase in FITC-dextran clearance. After a peak of 12 +/- 2-fold increase observed in the first 15 minutes into reperfusion, FITC-dextran 150 clearance decreased in magnitude and stabilized at about sixfold above baseline. Verapamil did not change the baseline clearance values. Importantly, verapamil inhibited the ischemia-induced increase in clearance and maintained the values at or near the baseline levels. We simultaneously determined the rate of release of 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane B2 (TXB2) into the suffusate. Verapamil decreased the baseline values of 6-keto-PGF1 alpha and increased those of TXB2. Verapamil inhibited the ischemia-reperfusion-induced increase in 6-keto-PGF1 alpha but did not alter the effect of ischemia-reperfusion on TXB2. Our main results demonstrate the effectiveness of verapamil in preventing microvascular alterations leading to increased leakage of macromolecules.

Animals↗
PubMed1990

Combined morphometrical and syntactic structure analysis as tools for histomorphological insight into human lung carcinoma growth.

Histological sections of formalin-fixed, paraffin-embedded tissue comprising 60 surgical specimens of human lung carcinoma were Feulgen stained. The histomorphological images were transferred to an automated image analysing system (VISIAC) and analysed as follows. The geometrical centers of tumor cell nuclei were defined as vertices, and the minimum spanning tree (MST) was calculated based on the two-dimensional distance between the vertices. Segmentation of the images was performed semiautomatically by interactive definition of nuclei of interest and automated detection of nuclear boundaries. Several morphometric features of tumor cell nuclei were measured including size, DNA-content (extinction), and form factor, and were set in relation to parameters of the MST. The following results were obtained: DNA-content and tumor cell nucleus size ('center cell') of different microscopic tumor growth patterns are related to the number of nearest neighboring cells. No relation was found in the neighboring (surrounding) cells. The different cell types of lung carcinoma, i.e., the different microscopic tumor textures expressed the relation of center cell features to the parameters of MST. A high amount of DNA content in branching points of the MST for epidermoid carcinoma may be interpreted as carcinoma growing in epidermoid textures tend to proliferate from tumor cell nuclei related to at least one neighboring cell. The opposite was found for large cell anaplastic carcinoma (no perceptible microscopic textures of the tumors) which showed the highest DNA content in tumor cell nuclei but which was not related to any neighboring cells. This technique allows analysis of growth centers and microenvironment conditions in human lung cancer in relation to tumor texture at the light microscopy level.

Adenocarcinoma↗
PubMed1990

[Representative epidemiologic study of influence factors on the periodontal loss of attachment].

The influence of age, inflammation intensity, tooth surface quality (caries, fillings), as well as mucogingival conditions on the loss of attachment was examined in 2000 probands. The loss of attachment was subdivided into periodontal pocket-formation and recessions. Determining cause is not the age but the inflammatory degree even if there is a significant increase of the attachment loss from age group to age group. The main part of the attachment loss increasing with advancing age is caused by recession development. Then, the individual dispersion is very high. Incorrect restorations, caries but also correct fillings increase periodontal disease. Mucogingival conditions show importance only in extreme case. There are less inflammations with pocket-formation than recessions. A preventive oriented basic care of the population is necessary to reduce irreversible damages of the periodontium.

Adolescent↗
PubMed1989

Beta-adrenoceptor blocking activity of diprafenone in anesthetized dogs: comparison with propafenone and propranolol.

The effects of diprafenone, a new class Ic antiarrhythmic agent, on canine hemodynamics and cardiac membrane beta-receptor antagonist binding activity, were compared with those of propafenone and propranolol. Mongrel dogs (4-5/group) were anesthetized intravenously (i.v.) with pentobarbital sodium (35 mg/kg) and instrumented for measurement of aortic and coronary blood flows (AF, CBF), blood pressure (BP), and heart rate (HR). Isoproterenol (ISO) was administered as bolus injections before (0.01, 0.03, and 0.1 micrograms/kg, i.v.) and after (0.01-3 micrograms/kg, i.v.) infusions of diprafenone or propafenone (0.3, 1, and 3 mg/kg) or propranolol (0.03, 0.1, and 0.3 mg/kg, i.v.). The ability of the antiarrhythmic agents to displace [3H]dihydroalprenolol (DHA) binding from isolated cardiac ventricular membranes in vitro was also evaluated. Each antiarrhythmic agent blocked the HR and BP responses to ISO in a competitive manner and decreased the specific binding of DHA to cardiac ventricular membranes. Propranolol was 2 to 7 times more potent as a beta-receptor blocking agent than diprafenone, which was 6 times more potent than propafenone. The equilibrium dissociation constants (Ki) for displacement of DHA by propranolol, diprafenone, and propafenone were 2.7, 14.3, and 252 nM, respectively, and have the same rank order of potency for in vivo inhibition of BP and HR responses to ISO. Diprafenone has significant beta-adrenoceptor blocking activity which may contribute to its efficacy as an antiarrhythmic agent and allow its use in treatment of arrhythmias refractory to therapy with class I and class II agents alone.

Adrenergic beta-Antagonists↗
PubMed1989

Tumour suppressor genes: oncogenesis update.

Evidence for tumour suppressor genes (anti-oncogenes, hemerogenes, flatogenes) has been obtained from the behaviour of familial childhood tumours in man, tumours in Drosophila caused by recessive mutations, experiments on fusing tumour cells to normal cells in tissue culture and revertants of oncogene-transformed cells. They may comprise more than one class of genes, one of which is likely to consist of genes responsible for normal differentiation. In large long-lived animals like man, which have a large potential somatic mutational load, mutant genes are associated with autosomal dominant behaviour in families. The susceptible individuals inherit heterozygosity of the tumour gene but the emergence of a tumour appears to follow a second somatic mutational event which results in homozygosity or hemizygosity. Hence, in tumour cells the mutations behave in a recessive manner. Success in isolating the normal genes may provide new tools for antenatal diagnosis of carriers and open up the possibility of developing new gene therapy.

Animals↗
PubMed1989

c-Ha-ras gene bidirectional promoter expressed in vitro: location and regulation.

Increased transcriptional activity of the c-Ha-ras gene product is correlated with induction of several important human tumor types. For this reason, we have investigated the nature of the c-Ha-ras promoter and the factors that regulate its expression. Using S1 and primer extension analysis of c-Ha-ras RNA from EJ cells, we have identified 18 initiation sites within an upstream exon (exon -1) whose 3' end (the donor splice site [D]) is located 1,105 base pairs (bp) upstream of the ATG codon. The furthest-upstream initiation site is located -191 bp relative to D, and the furthest downstream is located -16 bp relative to D. Transient expression assays, in which a series of mutants spanning this region were ligated to a promoterless chloramphenicol acetyltransferase vector, functionally confirmed the position and extent of this promoter. Mutational analysis further located a 47-bp element located between -243 and -196 relative to D that up-regulated transcriptional activity of the promoter region by 20- to 40-fold. This region contained both a GC box known to bind SP1 and a CCAAT box. Insertion of a simian virus 40 enhancer 5' to the promoter up-regulated transcription from each initiation site by approximately 10- to 20-fold. We have also localized, both by chloramphenicol acetyltransferase assay and by S1 analysis, a strong promoter operating in the direction opposite that of the gene and originating immediately 5' to the 47-bp regulatory region. The reverse promoter was found to have nine initiation sites between -248 and -278 relative to D.

Animals↗
PubMed1989

Concentration dependent effects of calcium blockade on vessel diameter and microvascular macromolecular clearance.

The dose-dependents effects of topically applied verapamil (a calcium entry blocker) on vessel diameter and macromolecular clearance (as an index of permeability) were investigated in the hamster cheek pouch. Verapamil at concentrations between 10(-10)M and 10(-7)M produced a gradual and parallel increase in both vessel diameter and in macromolecular clearance. At concentrations between 10(-7)M and 10(-5)M verapamil greatly increased macromolecular transport, but only modestly increased vessel diameter. Our data indicate that low doses of verapamil influence microvascular transport by modulation of flow and associated changes in microvascular pressure, while doses of verapamil greater than or equal to 10(-7)M produce a more direct effect on microvascular permselectivity.

Animals↗
PubMed1989

Effect of vitamin E on lipid components of atherogenic rats.

Rats were made atherogenic by feeding a synthetic diet containing high fat (20%) and cholesterol (2%) for two, three or four weeks. For alpha-tocopherol acetate supplementation studies, the rats on atherogenic diet for two weeks received alpha-tocopherol acetate 5 mg or 20 mg/100 g body weight once daily, orally for two weeks along with the atherogenic diet. Atherogenic diet fed rats showed elevated plasma cholesterol, hepatic total lipids, triglycerides and cholesterol and the increase in the constituents paralleled the period of feeding the diet. Administration of alpha-tocopherol acetate lowered the plasma cholesterol and hepatic lipid components in a dose-dependent manner. Supplementation with alpha-tocopherol acetate reduced the elevated osmotic fragility of erythrocytes from atherogenic diet fed rats to that of control levels. Thus alpha-tocopherol acetate administration to experimental atherogenic rats could normalize the altered lipid profile of atherogenesis and thereby reduce the risk for infarction.

Animals↗
PubMed1988

An in vitro evaluation of the hemostatic activity of topical agents.

An in vitro method has been developed for human non-anticoagulated blood to evaluate the enhancing effect of hemostatic agents on both plasmatic and cellular activation of the coagulation cascade. The coagulation time and the sequential generation of fibrinopeptide A (FpA) have been used as parameters. The kinetics of generation of FpA has been modelized and mathematically analyzed using the latence time, the slope of the linear part of the curve, and the time necessary to reach half maximal amplitude of FpA in the tube. A maximal amplitude of FpA in the tube. A very precise evaluation of the hemostatic activity of five different molecules, four being collagenous in nature, is given.

Analysis of Variance↗
PubMed1988

In vitro interactions of gadolinium DOTA meglumine and gadolinium DTPA meglumine on hemostasis.

The interactions of two gadolinium complexes (Gd-DOTA meglumine and Gd-DTPA meglumine) with hemostatic function have been analyzed using: (1) coagulation reactions (extrinsic and intrinsic pathways and fibrinoformation) and (2) platelet function investigations (aggregation, release of Ca++ and ATP after stimulation with collagen 2.5 micrograms/mL). The data obtained with Gd-DTPA meglumine (Mgl) exhibited a significant increase of the intrinsic coagulation pathway and a delay in fibrinoformation, although there is no alteration of the effect of thrombin on fibrinogen (fibrinopeptid A determinations). Platelet aggregation and release are moderately modified. In contrast, Gd-DOTA Mgl exerts no effect on the coagulation system and only minor effects on platelet functions. It is suggested that at least one mechanism involves the complexation of ionized calcium because Gd-DTPA Mgl and Gd-DOTA Mgl complex, respectively, 45% and 23% of ionized calcium in plasma. However, other mechanisms such as an alteration of fibrin polymerization are not unlikely.

Contrast Media↗
PubMed1988

Dose-response relationships between platelet activating factor and permeability--surface area product of FITC-dextran 150 in the hamster cheek pouch.

Changes in vascular permeability to FITC-dextran 150 associated with topical application of platelet activating factor (PAF) in the hamster cheek pouch preparation were calculated using a mathematical model (Baxter et al., Microvasc. Res. 34:336, 1987). Least square estimates of apparent permeability-surface area product (PS) and interstitial diffusion coefficient (D) were calculated from the data and the mathematical model using a Marquart optimization algorithm. Calculated PS products varied with applied PAF concentration while the best-fit estimate of apparent D remained constant at 10.5 X 10(-10) cm2/s. Average baseline PS was 16.5 X 10(-8) ml/s. PS increased to 45.2 X 10(-8) ml/s and 52.3 X 10(-8) ml/s with application of 10(-8)M and 10(-7)M PAF, respectively. A further increase in PAF concentration to 10(-6)M decreased the calculated PS product to 30.5 X 10(-8) ml/s. PAF is a potential modulator of macromolecular permeability in the microcirculation. This is the first study which quantitates the changes in PS of FITC-dextran 150 as a function of PAF concentration.

Animals↗
PubMed1988

Unfinished business.

The past 40 years have witnessed the development to maturity of molecular biology from its beginnings and determined attempts to apply this discipline in medicine, particularly to genetics, haematology, immunology and cancer research. However, although we have accumulated a detailed understanding of the genetic code and the mechanisms of the central dogma of molecular biology and have developed exquisitely sensitive and precise technologies, most recently represented by DNA recombinant techniques, many of the fundamental biological problems of 40 years ago still remain unsolved today. Some of these are listed and discussed.

Allergy and Immunology↗
PubMed1988

[In vitro study of the action of DOTA and DTPA-gadolinium complexes on platelet functions: aggregation and calcium excretion].

Interaction of 2 complexes of Gadolinium (DOTA Gd meglumin and DTPA Gd meglumin) was studied in vitro with regard to platelet function: aggregation and excretion of ATP and of ionised calcium in response to collagen (2.5 Ig/ml). Excretory functions were measured simultaneously with aggregation by bioluminescent techniques using luciferin for the measurements of ATP and aequorin for measurements of ionised calcium. Platelet aggregation and excretion functions, investigated in vitro, were moderately inhibited in the presence of gadolinium complexes. The greatest effects were seen with DTPA Gd meglumin. Complexation of extra-cellular ionised calcium by NMR products in partially responsible for the inhibition of platelet aggregation.

Adenosine Triphosphate↗
PubMed1988

[Pulsed Doppler sonographic determination of absolute flow velocities in the anterior cerebral artery in infants with hydrocephalus in comparison with a healthy patient sample].

In 52 infants (weight: 3174 +/- 1165 g; gestational age: 41.3 +/- 6.5 weeks) with hydrocephalus pulsed doppler recordings were obtained in the anterior cerebral arteries. For comparison 52 healthy infants (weight: 3148 +/- 1118 g; gestational age: 40.6 +/- 5.7 weeks) were investigated. In all children the maximal systolic velocity, the end-systolic velocity, the end-diastolic velocity and the pulsatility-index were measured. In the healthy control group the maximal systolic velocity was 43 +/- 14 cm x s-1, the end-systolic velocity 20 +/- 8 cm x s-1, the end-diastolic velocity 11 +/- 5 cm x s-1 and the pulsatility index was 0.75 +/- 0.10. All 9 children with minimal ventricular dilation without progression showed normal flow profiles with normal flow velocities and pulsatility-index in the anterior cerebral arteries. 17 infants with moderate, slowly progressive ventricular enlargement showed significant increase of the maximal systolic velocity (60 +/- 27 cm x s-1) and the pulsatility-index PI (0.82 +/- 0.14). There was no difference in the end-systolic and end-diastolic velocities to the healthy control group. 26 children with marked and rapid progressive hydrocephalus showed significant decrease of the end-systolic and end-diastolic velocities and an increase in the pulsatility-index. The end-systolic velocity was 15 +/- 7 cm x s-1, the end-diastolic velocity was 4 +/- 7 cm x s-1 and the pulsatility-index measured 0.91 +/- 0.18. There was no difference in the maximal systolic velocity which measured 41 +/- 17 cm x s-1. All children with increased intracranial pressure showed a pathological flow profile with a decrease of diastolic forward flow. Absent or retrograde diastolic flow in rapid progressive hydrocephalus may lead to a decrease of brain perfusion resulting in hypoxemic ischemic brain lesions. After implantation of a ventriculo-atrial shunt an increase in the end-systolic and end-diastolic velocities and a decrease of the pulsatility-index could be shown. Shunt insufficiency can be shown early by a decrease in diastolic forward flow.

Blood Flow Velocity↗
PubMed1987

Thromboresistance of bulk heparinized catheters in human.

Bulk heparinized catheters (1 mm internal diameter) containing 10% heparin ionically bound, were tested in four human volunteers. Catheters containing 0% and 10% heparin were compared in each individual using ultrasound microflow velocimetry, permeability test, sequential determinations of activated partial thromboplastin time, heparin levels and generation of Fibrinopeptide A, beta thromboglobulin and Platelet factor 4. Although the release of heparin expressed by its anti-IIa activity is of similar range in the four individuals the release of anti-Xa activity is variable and generally of greater magnitude, suggesting a privileged migration of low molecular weight components of heparin. These antiproteasic activities of heparin are sufficient to inhibit fibrin formation and blood coagulation despite their relative inability to prevent platelet activation.

Catheters, Indwelling↗