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Biomedical subjects

B Schmidt

Publications and source records attributed to B Schmidt.

At least 487 records · Page 27Linked to original sources

Current status of membrane plasma separation and plasma filtration techniques.

Blood and plasma processing by membranes was introduced into clinical medicine in 1979. In the meantime, membrane plasma separation (plasmapheresis) has become very satisfactory and is now a routine therapeutic procedure in many apheresis centers. Plasma fractionation by membranes (plasma filtration or cascade filtration) for unselective removal of high molecular weight pathogens from the separated plasma is technically possible but its routine clinical application is still limited to a few diseases with at least IgM-sized target proteins. The separation of IgG from albumin needed to treat many autoimmune diseases requires further development of both the membranes and the filtration technology.

Filtration↗

Processing peptidase of Neurospora mitochondria. Two-step cleavage of imported ATPase subunit 9.

Subunit 9 (dicyclohexylcarbodiimide binding protein, 'proteolipid') of the mitochondrial F1F0-ATPase is a nuclearly coded protein in Neurospora crassa. It is synthesized on free cytoplasmic ribosomes as a larger precursor with an NH2-terminal peptide extension. The peptide extension is cleaved off after transport of the protein into the mitochondria. A processing activity referred to as processing peptidase that cleaves the precursor to subunit 9 and other mitochondrial proteins is described and characterized using a cell-free system. Precursor synthesized in vitro was incubated with extracts of mitochondria. Processing peptidase required Mn2+ for its activity. Localization studies suggested that it is a soluble component of the mitochondrial matrix. The precursor was cleaved in two sequential steps via an intermediate-sized polypeptide. The intermediate form in the processing of subunit 9 was also seen in vivo and upon import of the precursor into isolated mitochondria in vitro. The two cleavage sites in the precursor molecule were determined. The data indicate that: the correct NH2-terminus of the mature protein was generated, the NH2-terminal amino acid of the intermediate-sized polypeptide is isoleucine in position -31. The cleavage sites show similarity of primary structure. It is concluded that processing peptidase removes the peptide extension from the precursor to subunit 9 (and probably other precursors) after translocation of these polypeptides (or the NH2-terminal part of these polypeptides) into the matrix space of mitochondria.

Adenosine Triphosphatases↗

Blockade of GABA receptors in periventricular forebrain of anesthetized cats: effects on heart rate, arterial pressure, and hindlimb vascular resistance.

Pharmacologic antagonism of GABAergic inhibition in the periventricular forebrain of anesthetized cats caused dose related sympathetically mediated increases in heart rate and arterial pressure in vagotomized cats, and suppression of reflex vagal activation in vagus-intact preparations where sympathetic effects are prevented by cervical spinal cord transection. In the present study performed in cats with intact autonomic pathways, similar administration of the GABA antagonist bicuculline methiodide (BMI) produced dose-related increases in arterial pressure, heart rate, and, when perfusion pressure in the autoperfused hindlimb was measured, vascular resistance. Furthermore, the relationship between heart rate and hindlimb vascular resistance changes suggested that the effects on heart rate reflected the combined sympathetic and vagal baroreflex effects of BMI. Intraventricular administration of muscimol, a potent GABA agonist, elicited abrupt and parallel reversal of BMI-induced effects on systemic arterial pressure and vascular resistance while attempts to acutely denervate the hindlimb at the height of the BMI response by cutting the femoral and sciatic nerves sharply reversed the increase in hindlimb vascular resistance in most experiments. The results suggest that the cardiovascular changes observed represent an integrated pattern consisting of excitation of sympathetic nerves innervating the heart and vasculature along with suppression of reflex evoked vagal excitability.

Adrenergic Fibers↗

Membrane plasma exchange: principles and application techniques.

Membrane plasmapheresis was introduced in 1978 as a new method for performing therapeutic plasma exchange. Its principal advantages over traditional techniques include speed, ease of performance, and ready adaptability to clinical centers already performing routine extracorporeal therapy. The appearance of a membrane plasmapheresis circuit (vascular access, anticoagulation, connectology) is similar to that of hemodialysis and especially hemofiltration; the operating protocols (treatment time, filtration rates, pressures, pharmacokinetics) are quite different. Particular attention must be paid to avoiding operating conditions that lead to hemolysis. In clinical use membrane plasma separation is as effective as centrifugal plasma exchange in removing plasma proteins. The sieving coefficients for proteins with a molecular weight (MW) ranging from 67,000 (albumin) to 2,400,000 (beta-lipoprotein) daltons are unity. An exchange of one patient plasma volume has been shown to cause a 55% reduction of the serum levels of intravascular proteins. There are no significant differences between membrane and centrifugal plasmapheresis in substitution fluid requirements (human albumin or fresh frozen plasma), indications for treatment and complications. The next major advance in plasmapheresis technology will almost certainly be development of a "closed loop" circuit in which filtered plasma is treated to remove the offending moiety and returned to the patient. This would eliminate both the cost and the possible side effects of replacement fluid. Membrane-based systems are already available for removing cryoglobulins or proteins with MW of at least 900,000 daltons.

Anticoagulants↗

Plasma elimination of antithrombin III (heparin cofactor activity) is accelerated in term newborn infants.

Antithrombin III (AT III) levels are markedly increased in newborn infants following exchange transfusion with adult blood, and subsequently return to pre-exchange values. This transient rise in AT III (heparin cofactor activity), was used to estimate its plasma elimination half-life. AT III activities were measured serially, before and after double-volume exchange transfusions with heparinised blood in newborn infants requiring therapy for severe hyperbilirubinaemia. The plasma elimination half-life of AT III activity was calculated to be 3.9 +/- 1.4 h (mean +/- SEM). Compared with published data on the kinetics of AT III infusions in adults, the neonate has a considerably accelerated turnover. This finding has important implications for the design of future therapeutic trials of AT III concentrates and provides further evidence that plasma proteins, including components of the coagulation system, appear to have different kinetics in the neonatal period.

Antithrombin III↗

Isolation of immortal cell lines from the first stage of murine leukemia virus-induced leukemia.

Friend murine leukemia virus (F-MuLV) is a replication-competent retrovirus that induces a rapidly fetal leukemia in susceptible mice (stage I disease). Leukemia cells obtained from these animals do not grow in cell culture using standard tissue culture conditions. However, in the presence of WEHI-3 cell-conditioned medium (CM), 100% of spleen or bone marrow explants from diseased mice yield immortal cell lines. These cell lines exhibit the same growth properties, produce the same viruses, and express the same oncogenes as the leukemia cells found in mice with stage I disease. No cell lines were obtained from leukemic mice in the absence of CM. No cell lines were obtained from uninfected adult, newborn, or phenylhydrazine-treated animals with or without CM. We conclude that some of the hematopoietic cells in F-MuLV-diseased mice will proliferate indefinitely in the presence of CM. The development of this abnormal response to CM is one of the early changes associated with F-MuLV-induced leukemia.

Animals↗

Analytical comparison of single-pass and dead-end operation in cascade filtration plasmapheresis.

Derived mathematical models are employed to compare cascade filtration plasmapheresis in the dead-end and single-pass formats. The high filtration fraction and low sieving coefficients associated with single-pass cascade filtration are shown to require treatment of the retentate concentration profile in an integrated rather than a length-averaged fashion. The models are best applied to specific simulations, but in general predict that (a) for a given membrane, the dead-end format will yield a higher albumin recovery but a lower macroglobulin rejection than single pass; (b) the single-pass format is more suited to loose membranes and the dead-end to tight membranes; and (c) in the single-pass but not the dead-end format, solute recovery is conveniently independent of the quantity filtered. Agreement between predicted and measured performance is good, although a larger data base would be required for complete validation of the models.

Models, Theoretical↗

Comparative evaluation of filters used in membrane plasmapheresis.

Protocols were developed for in vivo and in vitro characterization of the mass transfer performance of filters intended for use in membrane plasmapheresis. The protocols were applied to all presently available filters and also to secondary filters used in cascade filtration. Virtually no distinction was found in filtration rate or sieving coefficient of the ten plasma filters tested and all, except for one early model now considered obsolete, are clinically equivalent. In contrast, filters for cascade filtration varied widely in performance and still require further development for optimal use.

Filtration↗

Adenosine inhibition of catecholamine-induced increase in force of contraction in guinea-pig atrial and ventricular heart preparations. Evidence against a cyclic AMP- and cyclic GMP-dependent effect.

The antagonism between adenosine and isoprenaline on force of contraction, cyclic AMP (cAMP) and cyclic GMP (cGMP) content, adenylate cyclase activity and transmembrane action potential in isolated electrically driven atrial and ventricular muscle preparations from guinea-pig hearts was investigated. In atrial preparations adenosine added 5 min after isoprenaline decreased force of contraction. Adenosine abolished completely the positive inotropic effect of isoprenaline. Similarly, adenosine prevented the positive inotropic effect of isoprenaline when both substances were added simultaneously. In ventricular preparations adenosine also decreased the isoprenaline-induced increase in force of contraction. The effect was much smaller than it was in the atria. Adenosine reduced the isoprenaline-induced increase in force of contraction only by about 60%. Adenosine did not at all influence the positive inotropic effect of isoprenaline when both substances were added simultaneously. In both preparations the isoprenaline-induced increase in cAMP content of the intact contracting preparations was not diminished by adenosine. cGMP content remained unchanged too. Adenosine inhibited adenylate cyclase activity in broken cell preparations from both tissues. In atrial preparations the decrease in force of contraction of adenosine in the presence of isoprenaline was accompanied by a shortening of the action potential duration. In ventricular preparations adenosine failed to shorten the action potential. In conclusion, the effects of adenosine to inhibit the stimulatory action of isoprenaline on myocardial force of contraction are not due to changes in the cAMP and/or cGMP content. Instead, adenosine may inhibit a step beyond an increased cAMP level, e.g., may exert an inhibition of protein kinases. However, in the atria, but not in the ventricles, an additional direct effect of adenosine on transmembrane ion currents, most likely an increase in potassium conductance, probably is of even greater importance.

Adenosine↗

Thrombotic disease in newborn infants.

Thrombosis in newborn infants is probably more common that at any other period of life. This article highlights the neonate's tendency to develop thrombotic lesions, both in the absence and presence of indwelling catheters. Thrombosis associated with indwelling catheters is discussed in detail. Non-catheter-induced thrombosis is discussed along with its predisposing factors and the major sites of neonatal thrombi and their sequelae. An outline is then offered for a reasonable diagnostic and therapeutic approach.

Blood Vessels↗

A comparison of centrifugal and membrane-based apheresis formats.

Membrane and centrifugal apheresis operate on different physical principles but are both capable of efficiently fractionating plasma proteins from whole blood. For therapeutic purposes, both formats yield about the same protein clearance per liter of solute exchanged and neither is significantly more rapid than the other. Only continuous centrifugation can be used to pherese cellular elements and only membrane filter can be deployed in 'spontaneous' circuits. Hardware for continuous centrifugation is more expensive and disposables less expensive than for the membrane methods; the 'crossover' occurs at 200 treatments. To date, only the centrifugal method is employed for donor apheresis; this may change in the future as membranes can yield a truly platelet-free product and appear to offer a much more rapid collection cycle.

Blood Donors↗

[Pedicled craniopharyngioma of the 3d ventricle].

A 62 year-old man suffered of headache and progressive walking difficulties for 4 years. Radiological examinations showed a calcified intraventricular tumor attached to the floor of the 3rd ventricle. Death, caused by septicemia, occurred before neurosurgery. On sagittal braincut the tumor appeared pediculated and was attached to the anterior part of the floor of the 3rd ventricle. The microscopic features were those of typical craniopharyngioma. The pedicle and the floor of the 3rd ventricule were devoid of tumoral cells. Numerous large vessels which originated in the basal leptomeninges were present in the ventricular floor and the pedicle and then branched out into the tumor. Pathologically proven purely intraventricular craniopharyngiomas have been seldom reported. To our knowledge an autopsy case of pediculated intraventricular craniopharyngioma has been previously described only once, without particular attention to the pedicle. The integrity of the floor of the 3rd ventricle constitutes the only feature that may differentiate with certainty an intraventricular extension of a suprasellar craniopharyngioma from a pure intraventricular form of this tumor.

Cerebral Ventricle Neoplasms↗