[Experimental xenografting of kidneys. Operative procedure and technique of preservation (author's transl)].
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Biomedical subjects
Publications and source records attributed to D Bach.
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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.
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.
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.
The crucial factor in assessing the indication for implantation of a testis prosthesis is the mental status of the patient. Age and psychosocial considerations must be taken into account. The susceptibility to disturbance following of the loss of a testis differs among individuals. Most of the commercially available products can hardly be distinguished from a normal testis. The findings of a questionnaire in 88 patients with 106 prostheses are presented, according to which substitution of the testis with a prosthesis is not a superfluous therapeutic procedure. The man suffering from his "incompleteness" will be glad to have the implant if it restores to him the feeling of genital intactness. The practicing urologist assesses the indications and answers the questions resulting from emotional and psychic aspects of sexuality. The surgeon selects the appropriate implant and decides on the route of access and type of implantation.
The thermotropic behaviour of dipalmitoyl phosphatidylcholine analogues with a varying number (n) of CH2 groups between the phosphate and the quaternary ammonium has been investigated. The temperature (Tm) and the enthalpy (deltaH) of the phase transition are non-monotonous functions of the number of CH2 groups. Tm oscillates between 40 and 45 degrees C and deltaH between 7 and 13 kcal/mol for a variation of n between 2 and 11. It is concluded that the hydrocarbon chains in the head groups do not penetrate the hydrocarbon region and do not contribute directly to the melting of the acyl chains. It is suggested that their length may affect the critical balance between the attractive and the repulsive forces within the bidimensional lattice of the head groups. Copolypeptides of lysine with phenylalanine do not appreciably affect the Tm but have a pronounced effect on deltaH of the lipid phase transition, which depends strongly on the ratio of the two amino acids in the polypeptide. The effect of copolypeptide of any defined composition on deltaH is also a non-monotonous function of the number of CH2 groups in the phosphatidylcholine head group, but it does not parallel completely the oscilations in the Tm and deltaH of the pure lipids.
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Drug-membrane association of daunomycin, adriamycin and three of its derivatives, adriamycin-14-octanoate (AD-14-OCTA), adriamycin-14-acetate (AD-14-ACE) and N-trifluoroacetyladriamycin-14-valerate (AD32), was studied using phospholipid bilayers and human erythrocytes. The various drugs exhibited a differential affinity to membrane-lipid domains. Lipid-incorporated drugs exhibit a marked change in the shape of the emission spectrum which was utilized for the evaluation of the apparent dielectric constant, epsilon, of the environment surrounding the anthracycline moiety, as well as for the determination ofthe partitioning constant. By measuring the fluorescence polarization and the fluorescence lifetime of the incorporated drugs, rotational relaxation times of 4--8 ns were derived. These parameters provide a supportive evidence of the association of the fluorophore of the drugs with membrane-lipid domains. The anthracycline derivatives interact to a different degree with dipalmitoyl phosphatidylcholine and phosphatidylserine as reflected by changes in their thermotropic properties assessed by differential scanning calorimetry. Daunomycin was the most effective in decreasing the temperature of the phase transition and brought about a comparable reduction in the enthalpy of melting as AD32 and AD-14-OCTA. Adariamycin was the least potent of the series. AD-14-ACE and AD32 protected erythrocytes against hypotonic lysis, adriamycin and daunomycin had no significant effect on the susceptibility to hypotonic lysis, whereas AD-14-OCTA proved to be hemolytic even at low concentration (approx. 10(-7M).
Differential scanning calorimetry was employed for studying rat liver mitochondria and extracted mitochondrial lipids. Endothermic transition in the range 15--40 degrees C was detected for the whole mitochondria and between 10--20 degrees C for the extracted lipids.
Polymyxin B (PX) does not penetrate phospholipid monolayers and bilayers at low field strength across the lipid layers. The degree of penetration of PX is evaluated from its effect on the capacitance of the monolayers and on the conductance of the bilayers. PX added to one side of a bilayer causes its destabilization, it also enhances destabilization of lipid monolayers at positive electric fields across the surface layer in the direction of the adsorbed PX. PX lowers very little the fluorescence polarization of 1,6-diphenyl 1,3,5 hexatriene embedded in phospholipid vesicles. It is suggested that the penetration mechanism of PX into gram-negative bacteria is based on transient local breakdown of the plasma membrane.
Malignant lymphomas of the testis have a special position among the tumours of the testis. Also in such cases, in which only the testis is perceptibly diseased, nevertheless must be started from a systemic disease which is clinically not yet recognizable. These special problems demand a multidisciplinary, oncological collaboration in diagnostics and therapy. After establishment of the diagnosis and semicastration by the urologist further diagnostics and therapy should be performed by the representatives of other specialities.
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The thermal transitions of rat liver microsomes and isolated lipids were investigated by using differential scanning calorimetry. Endothermic transitions at approximately-5 degrees C and between approximately18 degrees and 40 degrees C were detected in the membranes and at approximately-10 degrees C and between approximately 10 degress and 20 degrees C in the extracted lipids. Interaction with delta1-tetrahydrocannabinol of microsomal membranes and of extracted lipids influences the thermotrophic behaviour as revealed by differential scanning calorimetry and eliminates the break in the Arrhenius plot of the enzymic activity of O-demethylase.
Malignant testicular tumors mainly occur in early adult life. 14 (7.8%) of our 180 patients with testicular tumors, treated from 1966 to 1976, were between 50 to 68 years of age. The pathological anatomical classification showed 9 germinal and 5 non-germinal tumors. To find out which tumor classification is the best for prognostic information and assessment of therapeutic consequences, we recommend setting up a central testicular tumor panel and register and refer to the multilateral study already initiated.
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The interaction of hashish compounds, delta 1-tetrahydrocannabinol and cannabidiol, with dipalmitoyl phosphatidylcholine was investigated using differential scanning calorimetry. Both drugs affect the transition of dipalmitoyl phosphatidylcholine from the gel to liquid crystalline state, decreasing both the melting temperature and the enthalpy of melting. At a drug to dipalmitoyl phosphatidylcholine ratio of approx. 1:5, two peaks appear in the transition profile, suggesting a phase separation in the drug dipalmitoyl phosphatidylcholine mixture.
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