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Biomedical subjects

M Kessler

Publications and source records attributed to M Kessler.

At least 433 records · Page 24Linked to original sources

[Prolonged functional times of xenogenic kidney transplants by means of anti-donor brain globulin (ADBG)].

This paper reports about experimental xenografting of kidneys in closely related species (fox-dog) modifying primary graft rejection by treatment of the recipients with anti-donor brain globulin (ADBG). ADBG, produced by immunisation of rabbits with fox brain tissue, in vitro demonstrates cytotoxicity against fox lymphocytes as well as versus dog lymphocytes. In respect of the phylogenetic constellations, the erythrocytes of both species, too, are influenced in hemagglutinating test. However, kidney tissue is said to be unable to adsorb thymocytolytic antibodies of anti brain sera, thus the way of immunosuppression is directed mostly against the lymphocytes of the recipients, causing here twofold survival time compared to untreated controls. MST is 11.2 +/- 2.4 days (n = 5). Cytotoxic antibodies appear on the 8th day after surgery, that means 4 days later than in the controls. Histological findings correspond to those of untreated recipients.

Animals↗

Na+-dependent, electroneutral L-ascorbate transport across brush border membrane vesicles from guinea pig small intestine.

In brush border vesicles from guinea pig small intestine L-ascorbate transport is Na+-dependent and electroneutral (in the presence of Na+, as shown by its lack of response to either positive or negative delta psi across the membrane). L-Ascorbate transporter has the kinetic characteristics of a mobile carrier (Km for L-ascorbate, 0.3 mM). D-Isoascorbate (erythorbate) seems to be another, but poorer, substrate of the same transporter. L-Ascorbate transport is subjected to heterologous inhibition by D-glucose.

Animals↗

Labeling of human erythrocyte membranes with eosin probes used for protein diffusion measurements: inhibition of anion transport and photo-oxidative inactivation of acetylcholinesterase.

The binding of eosin-isothiocyanate (eosin-NCS) and iodoacetamido-eosin (IA-eosin) to band 3 proteins in the membrane of human erythrocytes is characterized by studying the effect of these probes on the anion transport system. Although the unbrominated fluorescein precursors do not affect anion transport, both eosin labels are strong inhibitors of sulphate exchange in intact erythrocytes. 50% inhibition is obtained by binding 4.7 . 10(5) or 6.0 . 10(5) molecules/cell for eosin-NCS and IA-eosin, respectively. Both eosin probes are irreversibly bound and occupy common binding sites with 4,4-diisothiocyano-1,2-diphenyl-ethane-2,2'disulfonic acid (H2DIDS), although other sites are labeled as well. The inhibition of anion transport is light independent and can therefore not be attributed to a photosensitizing action of the eosin probes. Both eosin derivatives, however, inactivate acetylcholinesterase upon illumination of air-equilibrated samples of hemoglobin-free labeled ghosts. The inactivation of the enzyme is accompanied by the formation of protein aggregates as visualized by polyacrylamide gel electrophoresis. These effects are not observed when intact erythrocytes are illuminated in the presence of eosin probes suggesting a protective effect of hemoglobin during the labeling procedure. Protection of ghosts from photo-oxidation is achieved by displacing air with argon. These results are discussed in relation to the use of these and similar probes to measure protein diffusion in membranes.

Biological Transport, Active↗

A randomized double blind study of two oral contraceptives.

To study the question of whether one brand of oral contraceptives may be as acceptable as another for use of publicly-assisted family planning programs, a double blind study of two well-known brands, Ovral and Norinyl, was undertaken in Costa Rica and Trinidad. The pills were randomly assigned to 1,200 women. Common side effects - nausea, dizziness, vomiting, headaches - were associated with both Norinyl and Ovral. Differences in event rates for these conditions were much more marked by country than by the pill used. Ovral was associated with increases in skin problems, notably chloasma, in Cost Rica. A higher percentage of women using Norinyl reported intermenstrual bleeding and spotting in both countries. In Costa Rica continuation rates for Norinyl were adversely affected by this. With these exceptions there appear to be no important differences between the brands that would affect their use in family planning programs.

Adolescent↗

Extracellular potassium activity changes in the canine myocardium after acute coronary occlusion and the influence of beta-blockade.

Extracellular potassium activity before and after coronary occlusion was measured in the canine heart by means of potassium-selective surface electrodes. In the ischaemic myocardium potassium activity rapidly increased from a preocclusion value of 3.2 +/- 0.3 mmol.litre-1 to 10 +/- 0.6 mmol.litre-1 within the first 5 min and to about 11.3 +/- 0.5 mmol.litre-1 after 10 min of ischaemia (range from 9.5 to 14.5 mmol.litre-1). Following the initial 10 min of ischaemia no further increase was measured. In the non-ischaemic area potassium activity remained constant. Acute beta-blockade significantly attenuated the initial rate of increase in potassium activity; however, beta-blockade did not influence maximal values of extracellular potassium activity measured after occlusion. Lowering of heart rate by vagal stimulation did not modify the pattern of increase in potassium during acute ischaemia. Following ventricular fibrillation, a slow but continuous rise in potassium activity was found. These results demonstrate that extracellular potassium activity in the acutely ischaemic myocardium is considerably higher than indicated by the technique of coronary vein sampling and is in the range necessary for the development of re-entrant arrhythmias in the early phase after coronary occlusion.

Animals↗

[Hyperacute rejection of renal xenografts after presensitization of the recipients induced by treatment with donor species-specific spleen antigen (author's transl)].

This paper reports about experimental xenografting of kidneys in closely related species (fox/dog) modifying primary graft rejection by pretreatment of the recipients with semisoluble donor species-specific spleen antigen. This kind of pretreatment does not induce immunological enhancement which protects the graft from damage, but causes presensitization of the recipients and subsequently the hyperacute rejection of the transplants. Arteriovenous gradients of platelets and leukocytes as well as those of fibrinogen and clotting factors II, V, VIII, and IX suggest a greater degree of intravascular coagulation within the first minutes after revascularization. Hemagglutinating antibodies induced by pretreatment of the recipients with donor species-specific spleen extract seem to be responsible for the rapidity of rejection and for the reduction of survival time.

Animals↗

[The unaffected primary rejection of xenogeneic kidney transplants in the closely related fox-dog species system].

The present study reports of three kinds of experiments of unaffected primary rejection of xenogenous kidney transplanats in the close-related fox-dog species system. The issue is whether there is a relation between the amount of grafted parenchyma and the immune induced potency, that is whether the course of rejection of transplanted single kidneys (group I a) differs from the course after en-bloc transplantation of both kidneys (group I b). In group II alterations of blood chemism and behavior of humoral antibodies are followed in dogs to which a fox kidney was transplanted, while keeping their own functioning kidneys. This experiment is to give information whether the uremic syndrome influences the development of humoral immunity, and what changes of blood chemism may primarily be related to destruction of the graft, under the condition of absent uremia. Untreated graft recipients survived for 5,4 +/- 0,49 days (n = 5) when single kidneys were transplanted (group I a), and 5,2 +/- 0,75 days (n = 5) when both kidneys were grafted en-bloc (group I b). As to the rejecting reactions, both groups are almost equal: the increasing functional failure causes a fast increase of creatinine and urea nitrogen; alkaline phosphatase and LDH show distinct alterations, related to the progress of the graft's destruction. Decrease of albumin level and loss of cholinesterase activity indicate an impaired hepatic function as reaction to uremic intoxication. Gamma-globulins and leucocytes show alterations that can be related to non-specific inflammatory reactions. The immunologically specific initial lymphopenia suggests that after revascularization these cells migrate to the graft, and later react with antigenic structures of vascular endothelium and still later with those of the organ cells. Cytotoxic antibodies appear on the 4th postoperative day in increasing amount. Post mortem histologic examination shows round cell infiltrates in the vastly necrotic renal parenchyma. When the recipient's kidneys are kept in situ and a fox kidney is transplanted (group II) uremia is avoided and the animals survive. During the 30-days period of observation, that is longer than the term of rejection, the titer of cytotoxic antibodies remains stable or tends to increase. LDH and alkaline phosphatase show characteristic changes that are considered sequels from destructed transplantate. The experiments show, aside from certain reservations, that the donor-host combination fox-dog is suitable to serve as preclinic model for human transplantation using xenogenous donors of organs, i. e. anthropoid primates.

Animals↗

[Prolonged function time of xenogenic kidney transplants caused by the combined use of azathioprin and prednisolone].

The present publication reports about the delay of the rejection by unspecific medicamentous immuno suppression. This is the continuation of our earlier publication about the unaffected primary rejection of xenogenic kidney transplants in the closely related system fox - dog. The combined application of azathioprine and prednisolone leads to elongated function times of the kidney transplants and to the duplication of survival times of the recipients. Lymphocytotoxins, which are immuno-electrophoretic Ig G antibodies, appear two days later than in untreated recipients by hindrance of immunological reactivity. These obtain however then in consequence of the injured formation of antigen-antibody complexes a concentration increase which widely exceeds the increase of the control groups. The influence of azathioprin and prednisolone on the humoral respectively cellular immunity is talked about in the discussion. Morphological differences in the transplants are not observed in comparison with untreated recipients.

Animals↗

A simple apparatus for performing short-time (1--2 seconds) uptake measurements in small volumes; its application to D-glucose transport studies in brush border vesicles from rabbit jejunum and ileum.

An automated procedure allows uptake measurements with incubation times as short as 0.5 s and with volumes of 10--20 microliter. Using this technique the kinetic parameters Km and V of D-glucose transport in brush border vesicles from rabbit small intestine could be determined from unidirectional fluxes. A comparison of the data obtained from jejunum and from ileum shows that the Km for D-glucose is the same in both parts of the intestine, whereas the maximum flux is significantly larger in the jejunum.

Animals↗

Similarity in effects of Na+ gradients and membrane potentials on D-glucose transport by, and phlorizin binding to, vesicles derived from brush borders of rattit intestinal mucosal cells.

Both the presence of sodium and of an electrical potential difference across the membrane have been found to be necessary in order to achieve optimal D-glucose-protectable phlorizin binding to brush border membranes from rabbit small intestine. The effect of delta approximately muNa on phlorizin binding shows a close similarity to that on D-glucose transport, confirming that phlorizin is indeed bound to the D-glucose transporting protein. Possible modulations of binding by a transmembrane potential are discussed on the basis of some models.

Animals↗

[About the comparison of closely related species chimpanzee-man and fox-dog in respect of the possibility of xenotransplantation (author's transl)].

Although the transplant combinations chimpanzee-man on one hand and fox-dog on the other hand have nearly the same phylogenetic development within their zoological family, it is not quite correct to compare the immunological reactions and patterns of rejection of xenogeneic transplants within these systems. The differences in immunochemistry of serum proteins between these two systems confirm that chimpanzee and man are more closely related than fox and dog concerning their genetic disparity. This and other mentioned examples demonstrate the possibility of obtaining qualitative informations of genetic constellations between xenogeneic species combinations by comparing immunochemistry of serum proteins.

Animals↗

A modified procedure for the rapid preparation of efficiently transporting vesicles from small intestinal brush border membranes. Their use in investigating some properties of D-glucose and choline transport systems.

We have worked out a simplification of the procedure described by Schmitz et al. (Biochim. Biophys. Acta (1973) 323, 98--112) for the preparation of brush border membranes from small intestine. The procedure ultimately adopted is simple, rapid, does not necessarily require scraping and can be started from fresh or frozen material. It can be scaled up easily, allowing a quick production of large amounts of brush border membrane vesicles. These vesicles prove to be excellently suited for transport studies, as suggested by our measurements of D-glucose transport. Using these vesicles, the mode of choline transport across the brush border membrane was also investigated. Choline transport was found to occur by a saturable component with a Km of 83 +/- 4 micrometer (at 20 degrees C) and by a non-saturable component. It is independent of the presence of Na+ and appears to be non-electrogenic.

Animals↗