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Biomedical subjects

G Jacobs

Publications and source records attributed to G Jacobs.

At least 109 records · Page 6Linked to original sources

Some thoughts on a possible regulatory approach at EEC level on the classification and labeling of dangerous preparations.

At the present time no European directives on classification, packaging, and labeling exist which cover all dangerous preparations of chemicals. To develop such a directive, the Commission of the European Economic Community services, at the request of and in close collaboration with experts of the member states, has conceived a method for evaluating the toxicity of mixtures of chemicals. This method consists of (a) the characterization of each constituent by means of an index and (b) the classification of preparations for each route of administration on the basis of their toxicity. The index is a figure representing the degree of dilution needed to render the substance not dangerous in the sense of the EEC Directives on the classification of dangerous substances; the highest index among those obtained for acute and chronic toxicity is taken to characterize the substances. An indication of toxicity is obtained by applying the simple equation sigma (P X I), where P is the percentage and I is the index of each constituent. The most stringent classification among those obtained for the three routes of administration is taken for the final classification of the preparation on the basis of its acute and chronic toxicity. Other toxicological effects such as irritation, corrosion, sensitization, mutagenesis, teratogenesis, and carcinogenesis are not considered.

Animals↗

[Arterial digital subtraction angiography for demonstrating aortocoronary venous bypasses].

We examined the patency of aortocoronary venous bypasses in 51 patients during the early postoperative phase by using non-selective contrast injection into the aorta with digital subtraction angiography. In all patients it was possible to evaluate the degree of patency by this method. The accuracy and value of this examination, as compared with other invasive and non-invasive methods, is discussed.

Adult↗

[Functional images of the left ventricle using digital venous angiography].

Imaging and functional evaluation of the left ventricle are of great interest in cardiological diagnosis. So far, the left ventricle has been imaged by laevocardiography or by a nuclear medicine method (gated blood pool, first pass). The limited spatial and temporal resolution of nuclear methods and the invasiveness of selective laevocardiography are well known disadvantages of these techniques. With special software and hardware, it is possible to obtain functional images of the left ventricle by means of intravenous contrast injection; these provide definitive information concerning local myocardial contraction patterns.

Angiography↗

Human thoracic anatomy based on computed tomography for development of a totally implantable left ventricular assist system.

Human thoracic anatomy was studied using computed tomography (CT) for the development of a totally implantable electrohydraulic left ventricular system [Nimbus, Inc., and The Cleveland Clinic Foundation (CCF)]. To obtain statistical dimensional information for the chest wall, apex of the heart, and aorta, routine calibrated CT scans of 18 men and 17 women were analyzed. A special radiopaque vest was worn by the patient just prior to the scanning and X-ray procedures, so that each transverse scan could be assigned to a specific chest level after combination with a standard vertical referencing system set on the patient's radiogram. A polar coordinate system and direct measurement of transverse distances from the vertical column to points on the chest wall were employed to define collectively the shape and size of the intrathoracic surface of the chest wall. Locations of the aorta and apex were described by measuring their normalized distances from the midline and vertical column to the intrathoracic surface of the lateral and anterior chest wall. The radius of curvature of the intrathoracic wall lateral to the left ventricle was determined to be approximately 10.4 cm for the average adult male chest. The present CCF intrathoracic pump with this curvature fits fairly well in both the average and individual thoraxes of these adult males. The location of the aorta, particularly of the descending aorta, was used to determine the optimal outlet design. The most critical anatomical area was the apex location. For adult males, an average distance of 2.8 cm from the apex to the internal chest wall was found. Because of this small dimension, careful design of the inflow port is being performed to avoid anatomical mismatch.

Adult↗

Magnetic resonance signal intensity patterns obtained from continuous and pulsatile flow models.

The purpose of this investigation was to extend previous steady state flow studies with magnetic resonance (MR) to pulsatile flow measurements obtained with gated cardiac techniques in man with a pulsatile artificial heart device. Bovine blood and a solution of MnCl2 were studied. Correlation was made with complex and time-varying MR signals observed in the descending aorta on cardiac gated images obtained through the midthorax. MR signals from flowing fluids represent velocity distribution as shown in a velocity profile, and laminar flow is distinguished from nonlaminar. At very slow flow rates, signal intensity is lower than background. As the rate is increased, paradoxical enhancement occurs followed by loss of signal, which is complete at 7 liters per minute with fluid and 15 liters per minute with blood. These areas correspond to maximum fluid velocities of 41 and 88 cm/sec, respectively.

Animals↗

Isolation and characterization of a lectin from the snail Biomphalaria glabrata and a study of its combining site.

The hemagglutinins from the spawn of the water snail Biomphalaria glabrata were isolated by affinity chromatography on hog gastric mucin coupled to Sepharose 4B. The N-acetyl-D-glucosamine eluate (0.1 M) was fractionated further on Bio-Gel P-300, yielding two fractions. Fraction 1 had an Mr of 350 000 and displayed one band in immunoelectrophoresis, but was heterogeneous in discontinuous electrophoresis. It agglutinated human red blood cells with A1 and B specificity at concentrations of 12 and 72 micrograms nitrogen/ml, respectively. Fraction 2 had an Mr on gel filtration of 67 000 and was homogeneous in immuno- and polyacrylamide electrophoresis, and in isoelectrofocusing. It is composed of three subunits with Mr of 17 000 and one smaller subunit of 15 000. This fraction (lectin I) is a glycoprotein containing 6% hexoses and 2.5% hexosamines. For minimal agglutination of human A1 and B red blood cells 2.4 and 72.0 micrograms nitrogen/ml, respectively, of lectin I were required. O red blood cells were not agglutinated. Lectin I precipitated well with a human blood group substance of A1 specificity, moderately with a B- and poorly with an H-substance. Precipitin-inhibition studies revealed that among other sugars N-acetylneuraminic acid was the most potent inhibitor. Immunofluorescence studies confirmed the good interaction of lectin I with receptors of A1 and B erythrocytes and the failure of lectin I to attach to O-erythrocytes. Since N-acetylneuraminic acid is present on the cell surface of all human erythrocytes, it cannot be the dominant part of the receptor for the B. glabrata lectin I, despite its effectiveness as an inhibitor.

ABO Blood-Group System↗

Comparison of inhibitors of S-adenosylmethionine decarboxylase from different species.

S-Adenosyl-L-methionine decarboxylases were purified from rat ventral prostate, yeast (Saccharomyces cerevisiae), slime mould (Physarum polycephalum) and bacteria (Escherichia coli) and tested for inhibition by a variety of nucleosides related to S-adenosylmethionine and by methyl- and ethyl-glyoxal bis(guanylhydrazone). Although the enzymes from these different sources are markedly different with respect to activation by cations, the inhibition by nucleosides was quite similar. Very little inhibition was seen when analogues of S-adenosylmethionine with a different base were tested or when the ribose ring was opened or the positive charge on the sulphur atom was not present. Some derivatives in which the amino acid portion of the molecule was altered were more potent inhibitors, but again there was little difference between the enzymes from different sources. 5'-(Dimethylsulphonio)-5'-deoxyadenosine and S-adenosyl-3-methylthiopropylamine were the most inhibitory substances and had similar Ki values, suggesting that the aminopropyl group does not contribute significantly to the binding. All of the S-adenosylmethionine decarboxylases were strongly competitively inhibited by methylglyoxal bis(guanylhydrazone) and even more powerfully by its ethyl analogue, although the putrescine-activated enzymes from prostate and yeast were more sensitive than the bacterial and slime-mould enzymes. All of the S-adenosylmethionine decarboxylases tested bound to a column of methylglyoxal bis(guanylhydrazone) linked to Sepharose and were not eluted by 0.5 M-NaCl, but could be released by 1 mM concentrations of the drug, providing a rapid and efficient method for their purification.

Adenosylmethionine Decarboxylase↗

Immunohistochemical studies on the distribution and the function of the D-galactose-specific lectins in the sponge Axinella polypoides (Schmidt).

The distribution of the two D-galactose-specific lectins within the sponge tissue of Axinella polypoides was studied by autoradiography and by an immunohistochemical method on paraplast- and cryosections. Both techniques revealed that the lectins are stored inside the vesicles of the spherulous cells. All spherulous cells, regardless of their appearance in the different types of tissue contained the lectins. Antibodies were purified from an antiserum that reacted with both lectin I and lectin II and from the same antiserum rendered monospecific for lectin I. The purified antibodies were used to demonstrate that lectin II is predominantly present in spherulous cells with small vesicles, and lectin I in those with large vesicles. Electron-microscopic studies revealed that the spherulous cells with small vesicles are derived from archaeocytes and transformed into spherulous cells with large vesicles, a process accompanied by the conversion of lectin II to lectin I. Histological investigations showed that the tips of the bush-like, branched sponge lack the central axis, a spongin fiber network that provides support and stability to the sponge tissue. However, the missing spongin network is already preformed by cell bundles that ultimately produce the numerous fiber strands of the central axis. These bundles are composed exclusively of spindle-shaped cells and the spherulous cells. Other areas where production of spongin fibers is expected are also enriched with spherulous cells. These findings and the reaction of lectin-specific antibodies with the spongin fibers indicate that spherulous cells, and thus the lectins, are involved in synthesis of spongin fiber. Sponges lacking spongin fibers, e.g. Aaptos aaptos and Geodia cydonium, produce lectins with different carbohydrate specificity and possess large numbers of spherulous cells.

Animals↗

Experimental results for chronic left ventricular assist and total artificial heart development.

After more than 20 years of research on the artificial heart, it is now accepted that the pneumatically actuated total artificial heart can maintain near-normal physiology in experimental animals for several months. Such systems are clinically acceptable for short-term application (a few months) in patients waiting for a suitable heart transplant. However, realistically, a cardiac prosthesis that has the capability of being totally implantable for over 2 years must be available. Based on this premise, our group initiated the development of a mechanically actuated total artificial heart, capable of coupling with either a thermal or electrical actuation system. Since 1977, under the National Institutes of Health chronic left ventricular assist program, we have used two different pusher-plate pumps and electrical systems. Taking advantage of technology generated in these programs, we began developing a prosthesis to replace the total cardiac function. This paper is a summary of both the chronic left ventricular assist and total artificial heart development progress in this laboratory.

Animals↗

Incorporation of [1-14C]acetate into fatty acids and aliphatic moieties of glycerolipids in Leishmania donov ani promastigotes.

1. Short-time incubations (20-300 sec) of Leishmania donovani with [1-14C] acetate showed lauric, myristic and palmitic acid to be labeled first, whereas from 150 sec on the radioactivity was mainly found in stearic and oleic acid. 2. After an incubation period of 7 days the distribution of radioactivity in fatty acids was similar to the mass distribution of fatty acids. 3. Up to 300 sec 14C-activity was present mainly in acyl moieties of lipids (94%). 4. Ether moieties of radylglycerols, diradylglycerophosphoethanolamine and -inositol slowly incorporated radioactivity in pulse-chase experiments from 1 to 24 hr. 5. Pulse-chase experiments revealed significant differences in plasmanylethanolamine, acylglycerol and sterol metabolism of cells in the logarithmic or stationary phase of growth.

Acetates↗