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Biomedical subjects

S Rapoport

Publications and source records attributed to S Rapoport.

At least 73 records · Page 4Linked to original sources
PubMed1980

Reversible osmotic blood-brain barrier disruption in humans: implications for the chemotherapy of malignant brain tumors.

The blood-brain barrier seems to be an important factor in drug access to malignant brain tumors. Successful experimental reversible disruption of the blood-brain barrier in animals provided the basis for a clinical evaluation of osmotic disruption in five patients with primary and metastatic malignant brain tumors. Good to excellent blood-brain barrier disruption was achieved in four patients with a single nontransient complication, a superficial wound infection at the burr hole site in the first patient. Reversible, transient osmotic barrier disruption was achieved 15 times in five patients without additional toxicity. Computed tomography and radionuclide brain imaging were shown to be useful noninvasive monitors of the adequacy and extent of barrier disruption. These studies also provide further evidence that the barrier is at least partially intact in human tumors because in one patient a metastsis was seen only after barrier disruption.

Adenocarcinoma↗
PubMed1980

[Electron transport particles from bovine heart as a test system in toxicological studies].

14 standard respiratory inhibitors and substances of toxicological interest were tested on the NADH oxidase and the succinate-cytochrome c oxidoreductase systems of beef heart electron transfer particles (ETP) in the presence and absence of human serum albumin (HSA). HSA did not influence the half-inhibition concentrations by cyanide, amytal and antimycin A. It had little effect on the inhibition by rotenone or carboxin, whereas the inhibition by free fatty acids and monoglyceride was greatly decreased. Lindan and DDT exerted a marked inhibition of the NADH oxidase system in the absence of HSA; the inhibition was weaker but still considerable in the presence of HSA. In the presence of HSA 10(-4) M DDT but not Lindan inhibited also the succinate-cytochrome c reductase system. The results show that ETP may be a useful test object in toxicological studies.

Amobarbital↗
PubMed1980

Creatine transport into red blood cells.

The permeation of creatine from plasma into normal human red blood cells was investigated by means of 1-[14C]-creatine. Two statistically different Vmax and Km values were found for lower and for higher creatine concentrations of the plasma, respectively, indicating two types of transport with different affinities and capacities. It is suggested that the high affinity process, which accounts for 1/4 of the capacity and has an affinity constant of 0.087 +/- 0.032 mM is an active transport, while the low affinity transport represents an exchange diffusion. There is little, if any, effect of pH in the range of 6.9-7.9 on the transport. The total creatine concentration of the red cells did not change significantly even with high creatine concentration of the plasma during 6 h incubation at 37 degrees C. The in vitro experiments showed a daily exchange of cellular creatine of 20%, the t0.5 being about 2.5 days.

Adult↗
PubMed1979

Reflex connexions of motoneurones of muscles involved in head movement in the cat.

1. The reflex connexions from muscle afferents and ventral root fibres to the motoneurones of the muscles biventer-cervicis, complexus, sternocleidomastoid, trapezius and splenius, the principal muscles involved in head movement in the cat, were studied with the technique of intracellular recording. 2. Electrical stimulation of homonymous muscle afferents of biventer-cervicis and complexus, sternocleidomastoid and trapezius, at strengths below 1.6 times threshold of the dorsal root afferent volley, produced monosynaptic e.p.s.p.s in the corresponding motoneurones. Recruitment of higher threshold muscle afferents produced additional p.s.p.s with longer central delays. 3. Stimulation of low-threshold muscle afferents did not produce any p.s.p.s in the motoneurones of the ipsilateral antagonist. Stimulation of higher threshold afferents evoked i.p.s.p.s with central delays longer than 1.6 msec, or mixed e.p.s.p.-i.p.s.p.s in the ipsilateral antagonist. 4. Mixed e.p.s.p.-i.p.s.p.s or i.p.s.p.s with central delays longer than 1.5 msec were evoked in trapezius motoneurones upon stimulation of high threshold afferents from biventer-cervicis and complexus, while stimulation of low-threshold biventercervicis and complexus afferents evoked no p.s.p.s in trapezius motoneurones. 5. Stimulation of contralateral low-threshold biventer-cervicis and complexus afferents evoked a sequence of i.p.s.p. disinhibition in sternocleidomastoid motoneurones, and vice versa, with central delays longer than 1.7 msec. 6. Stimulation of the deafferented biventer-cervicis, complexus, splenius, sternocleidomastoid and trapezius muscle nerves frequently activated interneurones in the ventral horn at monosynaptic central delays. Activation of homoynmous ventral root fibres rarely evoked p.s.p.s in biventer-cervicis, complexius, splenius or sternocleidomastoid motoneurones, while it produced disynaptic i.p.s.p.s in 80% of trapezius motoneurones. 7. It is concluded that Ia reciprocal inhibition and recurrent inhibition, two reflex circuits which are so prominent in limb segments of the spinal cord, do not play a major role in the generation of head movement. Rather, head movement may be primarily controlled from supraspinal centres.

Animals↗
PubMed1979

[Selectivity of action of the lipoxygenase from rabbit reticulocytes on mitochondria and erythrocyte membranes].

Whereas the lipoxygenase from rabbit reticulocytes caused a large formation of malonyl dialdehyde (MDA) with rat liver mitochondria, erythrocyte ghosts were attacked only slightly independently of their type of preparation. The formation of MDA was not enhanced by release of spectrin-actin from the ghosts. The lipoxygenase did not give rise to hemolysis of intact erythrocytes. The formation of MDA was increased by heat treatment of the ghosts. Addition of cholesterol to a phospholipid emulsion inhibited the formation of MDA by the reticulocyte lipoxygenase. These results indicate that both lipid-protein interactions and the cholesterol content of the membranes may be involved in the preferential attack of the lipoxygenase on mitochondrial membranes.

Animals↗
PubMed1979

NADPH production in the oxidative pentose phosphate pathway as source of reducing equivalents in glycolysis of human red cells in vitro.

Studies have been carried out on human erythrocytes in vitro to clarify the deficit of pyruvate formation under conditions when 2,3 DPG is degraded. The results lead to the conclusion that there exist a cross connection between the glycolytic and the oxidative pentose phosphate pathway which is mediated by the NADP/NADPH couple. NADPH serves as additional reducing equivalent in the reaction of the LDH. In the absence of glucose the pool of the metabolites of the pentose phosphate pathway is able to supply glucose-6-phosphate for the production of NADPH by recombination. The reaction of NADPH at the LDH is probably of significance under in vivo conditions.

Diphosphoglyceric Acids↗
PubMed1979

The breakdown of adenine nucleotides in glucose-depleted human red cells.

1) The rate of 2,3-bisphosphoglycerate breakdown is independent of pH value. 2) The adenine nucleotide pattern at alkaline pH values with its characteristic lowering of ATP and the accompanying accumulation of fructose-1,6-bisphosphate is caused by a relative excess of the activity of the hexokinase-phosphofructokinase system as compared wity pyruvate kinase. 3) The breakdown of adenine nucleotides proceeds via AMP mainly through phosphatase and not via AMP deaminase. 4) The constancy of the sum of nucleotides as long as glucose is present is postulated to be due to resynthesis via adenosine kinase which competes successfully with adenosine deaminase. 5) A procedure is given to calculate ATPase activity of glucose-depleted red cells. The results indicate that the ATPase activity is less at lower pH values and declines with time. An ATPase with a high Km for ATP is postulated. 6) During glucose depletion ATP production is mostly derived from the breakdown of 2,3-bisphosphoglycerate and the supply from the pentose phosphate pool both of which proceed at a constant rate. The contribution of pentose phosphate from the breakdown of adenine nucleotides amounts to 40% of the lactate formed at pH 6.8 and is about twice the lactate at pH 8.1.

Adenine Nucleotides↗
PubMed1979

[In vitro maturation of rabbit reticulocytes: oxygen consumption reaction].

With a simple experimental system the changes of endogenous, antimycin A-suppressed, oligomycin-suppressed and antimycin A-resistant oxygen consumption are studied during the maturation of intact cells of the 6th day of bleeding. All functional characteristics of oxygen consumption decrease during maturation. The rate of decrease is strongly increased by high inorganic phosphate concentrations (125 mM). This effect is most obvious for the oligomycin-suppressed and the endogenous respiration. The degree of uncoupling of non-incubated cells is 14%. During 24 h incubation it rises to 75%. Inorganic phosphate accelerates the increase of uncoupling during maturation. Reticulocytes of the 4th day of bleeding are characterized by a higher respiratory capacity and also by a higher rate of maturation of antimycin A-suppressed and endogenous respiration. The degree of uncoupling does not increase during maturation. This may be attributed to the low lipoxygenase activity of these cells. 25% of the endogenous oxygen consumption of unmatured cells are antimycin A-resistant. This type of respiration declines by 50% in 4 h incubation irrespective of inorganic phosphate concentrations and day of bleeding. In nitrogen all functional characteristics of respiration during the maturation decline more rapidly than in oxygen. The antimycin A-resistant respiration, however decreased more slowly and reached 50% after 12 h. A pH dependence of maturation (maximum at pH 8.4) was found for the endogenous and the antimycin A-suppressed respiration. The degree of uncoupling rises most quickly at pH 7.4. This is possibly related to the pH maximum of lipoxygenase.

Animals↗
PubMed1979

[Free fatty acids as inhibitors of the respiratory chain in testicular homogenates].

The supernatants of the 440 000 . g . min centrifugation of homogenates of rat, bull and boar testicles and sperm inhibit the NADH-oxidase activity of non-phosphorylating submitochondrial particles (ETP). Whereas no inhibitory activity was observed with young rats (150 g), a marked inhibition was detected with heavier animals. The inhibitory activity of testicles was located in the microsomal fraction. The reaction of the testicular inhibitor with the ETP is initiated by an instant reversible binding followed by a slow irreversible inhibition of the electron transport. The reason of the time-dependence is neither an interaction between the enzymes of the ETP and those of the microsomal electron transport nor a slow degradation of the ETP by microsomal phospholipases. Some observations indicate an indirect involvement of phospholipase via the formation of free fatty acids (FFA). The inhibitory fraction could be solubilized from the microsomes both by sodium cholate treatment and by ethanol extraction. After separation of the lipid classes by chromatography on silica gel and gas-chromatographic analysis the inhibitory fraction was identified as a mixture of free fatty acids (FFA) of different chain lengths and degree of saturation. Thus a new effect of FFA on the mitochondrial electron transport has been detected which is different from other actions known up till now. The degradation of the phospholipids of the endoplasmic reticulum in the spermatozoa may be the source of the enhanced formation of FFA. An inhibition of the cell respiration presumably does not occur in vivo. The high FFA level in the testicular homogenates of sexually mature animals is a consequence of an intensive FFA metabolism, especially of high phospholipase activity.

Animals↗
PubMed1979

[Energy metabolism of the rat renal cortex, as measured by incubation in various substrates].

Different substrate mixtures were investigated for their effect on energy metabolism using sections of the rat renal cortex. Simultaneous determination of adenine nucleotide concentrations and determination of the damage quotient of oxidative phosphorylation proved to be appropriate parameters for selecting substrate mixtures that have a favorable effect on energy metabolism. A mixture of albumin (1 mM) and octanoate (5.6 mM) with electrolytes proved to be adequate. The extent of oxygen consumption (60%) and 14CO2 formation (75%) argues in favor of the metabolization of this mixture; a damage quotient of 23% and general constancy of the concentration of high-energy compounds render prospective their testing in animal experiments. Addition of dicarbosylic acids increase the antimycin A resistant oxygen consumption without any energy conservation being demonstrable. Therefore, these substrates should not be used for conservation.

Adenine Nucleotides↗
PubMed1978

Immunochemical studies on human glyceraldehyde-3-phosphate dehydrogenase.

Highly purified GAPD preparations from human erythrocytes and skeletal muscle have been used as immunogenes in rabbits. The antibodies produced readily precipitated their antigens and also inhibited their enzymatic activities. An immunochemical evaluation of the precipitability of both enzymes exhibited no immunochemical differences between them. Furthermore, the antibodies were tested against several tissue homogenates from man and revealed an identical precipitability. The identical cross-reactivity indicating a lack of antigenic differences support the absence of GAPD-isoenyzmes in man. The amount of GAPD in several organ extracts was estimated by the technique of single radial immunodiffusion. Furthermore it was demonstrated that the GAPD is bound to the membrane only under hypotonic conditions of hemolysis, while under approximated intracellular conditions of hemolysis the GAPD is not membrane bound.

Animals↗
PubMed1977

A mathematical model for the influence of anionic effectors on the phosphofructokinase from rat erythrocytes.

The influence of the positive effectors AMP, sulphate, glucose 1,6-bisphosphate and the negative effector 2,3-bisphosphoglycerate on rat erythrocyte phosphofructokinase has been investigated. The kinetic data have been fitted to the Monod-Wyman-Changeux model as well as to a model based on a closed association-dissociation equilibrium. The application of the fitting procedure yeilds for both models a good corresponding between theoretical and experimental data and equal results with respect to the action of the effectors on the enzyme. The corresponding dissociation constants for the binding of the positive effectors to the active state are: AMP 35 micronM, sulphate 0.43 mM and glucose 1,6-bisphosphate 15 micronM. 2,3-Bisphosphoglycerate as in inhibitor stabilizes the inactive state (dissociation constant: 1.4 mM). A preliminary discrimination between the Monod-Wyman-Changeux model and the association-dissociation model has been attempted.

Adenosine Monophosphate↗