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Biomedical subjects

G Wunderlich

Publications and source records attributed to G Wunderlich.

At least 55 records · Page 3Linked to original sources

Clearance of myelin constituents and axonal sprouting in the transected postcommissural fornix of the adult rat.

Following transection of the postcommissural fornix in the adult rat, fibres retract from the lesion zone but then start to regrow within their former pathway up to the lesion site, where they terminate. The fibres neither penetrate nor bypass this region. In order to define the molecular mechanisms that cause regenerative failure at the lesion site, we analysed the spatiotemporal relationship between clearance/re-expression of myelin constituents and axon sprouting. Using immunocytochemical methods, we investigated the distribution of myelin-associated growth inhibitor (NI-35/250) and myelin basic protein after transection of the postcommissural fornix. In the studies described here we demonstrate the sequential removal of neurofilaments and myelin constituents in a perilesion zone and at the lesion site. The removal of myelin constituents was followed by the extensive regrowth of fornix fibres in the proximal segment. However, these fibres stopped at the lesion site, an area that lacked immunostaining for NI-35/250 and. In the distal stump we observed the disappearance of neurofilament along the entire fornix segment but spatial differences in the removal of myelin constituents. While both NI-35/250 and myelin basic protein disappeared in the perilesion zone, they persisted in the more distal segment for at least 28 months after lesion. In conclusion, our study indicates that the onset of axon sprouting is correlated with the removal of myelin basic protein and NI-35/250. Furthermore, we suggest that it seems unlikely that the myelin growth inhibitor NI-35/250 constitutes the stop signal of the axon growth barrier in the transected formix.

Animals↗

Site-specific labelling of the oligosaccharide chains of antibodies.

This paper presents a new method for site-specific labelling of antibodies employing enzymatic reactions without oxidizing or reducing agents. IgG was first treated with immobilized sialidase from Clostridium perfringens to cleave bound NeuAc. CMP-9-deoxy-9-salizoyl-NeuAc, an activated sialic acid analogue, was labelled with 131I via the iodogen-method in high yields (> 95%). Then the oligosaccharide chains of antibodies were labelled yield with the radioactive NeuAc analogue by transfer using alpha-2,6-sialyltransferase from rat liver in 50%.

Animals↗

Transplants of immature astrocytes promote axonal regeneration in the adult rat brain.

To study beneficial effects of immature astrocytes on axonal regeneration in the injured adult mammalian brain, we have stereotactically implanted cultured astrocytes from embryonic (E 14-16) rat cerebral cortex into the lesion site following transection of the postcommissural fornix. The spatio-temporal pattern of axonal degeneration and regrowth in the proximal fornix stump was investigated using wheat germ agglutinin-horseradish peroxidase tracing techniques and quantitative analysis of myelinated axon profiles. Transection of the postcommissural fornix tract caused disintegration of the axons in the distal stump as well as rapid and pronounced retrograde axonal degeneration up to 800-1,200 microns proximal to the lesion site. While a small bundle of subicular fibers spontaneously extended to the lesion site within 4 weeks after injury, axonal regeneration was markedly stimulated in those animals that had received an astroglial implant. Following the former pathway, regenerating axons sprouted towards the implant but did not penetrate the graft. Instead, the axons elongated over the surface of the transplant, avoiding growth into the surrounding neuropil or into the distal fornix segment. In grafted animals we further observed a substantial increase in the number of myelinated axons of approximately 31.5% (at the level of 800 microns) and approximately 40% (at the 400 microns level) compared with the injured tract lacking a transplant. Our results indicate the capacity of juvenile astrocytes to stimulate axonal regeneration after injury of the post-commissural fornix tract in the adult rat brain. We further demonstrate myelination of the regenerated axons.

Animals↗

A new method for site-specific labelling of the oligosaccharide chain of antibodies: preliminary results.

There are various approaches for improving endoradiotherapy and diagnosis with monoclonal antibodies in nuclear medicine. The known methods of site-specific labelling of biomolecules based either on reactions with sulfhydryl groups or on reactions with aldehyde groups of the oligosaccharide chains effect unwanted alterations of the biomolecules. We present a new method to introduce radioactive halogens into the oligosaccharide chains of an antibody, based on the enzymatic transfer of the labelled synthetic sialic acid derivative CMP-9-deoxy-9-salizoyl-NeuAc. It was first labelled by the iodogen-method (iodine) in yields of more than 90%. Under selected conditions it was possible to obtain di- and trihalogenated products. Then the radioactive sialic acid derivatives were transferred during 90 minutes at room temperature with 2.6-sialyltransferase from rat liver into the oligosaccharide chains of antibodies. It is necessary to use neuraminidase pretreated antibodies with an increased number of binding sites for sialic acid derivatives. Yields of about 55% were obtained for the monoiodinated sialic acid derivative. With this method we present a reasonable alternative reaction of labelled compounds with biomolecules. Studies of the immunoreactivity are now in progress.

Animals↗

Genomic variability in the preS1 region and determination of routes of transmission of hepatitis B virus.

On the basis of published sequence data the preS1 attachment region of hepatitis B virus (HBV) appears to be highly variable. Using a novel method for rapid DNA sequencing by the polymerase chain reaction we screened 34 HBV DNA-positive sera for mutations in a variable part of the preS1 region of the HBV genome. The sequence data were used to analyse potential chains of infection, and strongly supported the expected routes of HBV transmission among patient groups. Furthermore, sequence comparisons permitted sub-genotyping of the viruses. In the 22 cases of subtype adw, we found a very low number of point mutations. This shows that the attachment site of HBV is more highly conserved than that of other blood-transmissible viruses such as human immunodeficiency virus or hepatitis C virus.

Amino Acid Sequence↗

[The Schultz-Hencke concept of psychosomatics].

It was quoted by Schultz-Hencke that psychosomatic diseases like psychic symptoms are understandable and possible to derive from the drivepsychologic theory of neurosis. Following the so called equality in time correlation which says that healthy and neurotic persons show a correlation between psychic action and organic action, neurotic symptoms may be understood as deriving from a partition of a drivecomplex which can show action on the psychic or organic part of a person. At the beginning of an organic symptom there is to be found a malfunction of an organ or in a functional complex from which an organic disorder will develop.

Drive↗

[Scintigraphy of sustained-release agar-embedded insulin suppositories].

In earlier publications [1-3] we reported on the retardation and protective effect of insulin-agar-embeddings in triglyceride suppositories by in vitro and in vivo tests on rabbits. The discovered effects were visually followed by gammascintigraphic test of adequate rectally applied 131I-insulin-specimens in the rectum and thyroid gland and, in relation with the glucose lowering course, the liberation, distribution and bioavailability of the immobilized hormone was illustrated.

Agar↗

Animal studies on the in vivo stability of 211At-labelled albumin particles.

The alpha-emitter astatine-211 appears as one of the most suitable representatives for radiotherapy owing to its excellent decay properties. We report the studies in mice on the stability of the astatine bond to HSA-particles. Microspheres stick fast in the lung capillaries. There is a comparatively very slow decrease of radioactivity in the lungs. The 211At-labelled microspheres appear quite stable in vivo compared with a series of other biomolecules and so give a potential possibility for using the excellent radiophysical features of 211At in endogenous therapy of malignant tumours.

Animals↗

[Griesinger's psychiatric approach].

The standpoint from which Griesinger considered mental illness and the closely connected relationship between body and mind is described. The conclusion is drawn that Griesinger, realising that body and mind form an entity with the brain as an organ and psychological processes as its function, regarded mental illness as an organopathological process. This played a great role in raising psychiatry to the status of the purely somatic fields of medicine.

Germany↗

Proteinases and inhibitors in plasma and peritoneal exudate in acute pancreatitis.

Examination of the peritoneal exudates of 12 patients with acute pancreatitis revealed high activities of pancreatic lipase and amylase. The immunologic levels of the plasma-derived inhibitors alpha 1-antitrypsin, antithrombin III and alpha 2-macroglobulin in the peritoneal exudates were not markedly different from those of the plasma. However, the inhibitory capacity of alpha 2-macroglobulin, the main inhibitor of human pancreatic trypsin in the exudate, was almost completely depleted when measured by an enzymatic method. Furthermore, spontaneous fibrinolysis occurred in 6 out of 13 exudates applied to plasminogen-free fibrin plates, indicating the presence of free proteinase. This fibrinolytic activity might be inhibited by exogenous alpha 2-macroglobulin or aprotinin (Trasylol, Bayer AG).

Acute Disease↗

[Ideler's (1835) psychodynamic theory].

In 1835 the Berlin psychiatrist Carl W. Ideler developed a psychodynamic theory describing the laws and dynamics of instincts within the spirit and the interaction between spirit and intellect. There are striking parallels to the psychoanalytical theory of Freud. These show in the economic view of psychic incidents and in the characterization and dominance of the instincts within the mental system. All the more Ideler described psychic incidents and phenomenons which Freud called for instance topography, duality of instincts, defence, the fact of being conscious and the unconscious.

Germany↗

Sequence diversity and linkage disequilibrium within the merozoite surface protein-1 (Msp-1) locus of Plasmodium falciparum: a longitudinal study in Brazil.

The merozoite surface protein-1 (MSP-1) is a major vaccine candidate for the asexual blood stage of malaria. We examined both the extent of sequence diversity in block 17, the 3' end of Msp-1 gene coding for a 19-kDa polypeptide (MSP-1(19)) putatively involved in red blood cell binding, and the patterns of linkage disequilibrium between polymorphic sites throughout the Msp-1 locus. The parasite population sample consisted of Plasmodium falciparum isolates collected between 1985 and 1998 in Rondĵnia, an area of hypoendemic malaria transmission in the southwestern Brazilian Amazon. Results were summarized as follows. (1) Seven block-17 sequence variants or haplotypes were found among 130 isolates, including two new haplotypes (novel combinations of previously reported amino acid replacements), here named Brazil-1 (E-TSR-F) and Brazil-2 (Q-TSR-F). (2) As previously shown for other Msp-1 polymorphisms, frequencies of block-17 haplotypes displayed significant temporal variation. (3) Extensive linkage disequilibrium was demonstrated between neighboring dimorphic sites within block 17, as well as between polymorphisms at the 5' and 3' ends of Msp-1 (map distance range: 3.83-4.99 kb). (4) The overall patterns of linkage disequilibrium within Msp-1 remained stable over a period of nearly one decade, and examples of possible 'epidemic' expansion of parasites carrying particular Msp-1 alleles were found in the 1980s and 1990s. These results are discussed in relation to the population biology of P. falciparum and the development of malaria vaccines based on MSP-1.

Alleles↗

Differential antibody recognition of four allelic variants of the merozoite surface protein-2 (MSP-2) of Plasmodium falciparum.

The merozoite surface protein-2 (MSP-2) is a major vaccine candidate for the asexual blood stage of Plasmodium falciparum. MSP-2 is essentially dimorphic, and allelic families are named after the representative isolates FC27 and IC1. The polymorphic central region contains immunodominant repeats, which vary in number, length, and sequence within and between allelic families. We have examined the antibody recognition of repeat regions from both MSP-2 allelic families expressed as recombinant fusion peptides. The results are summarized as follows. (1) Immunization of mice with the fusion peptides elicited IgG antibodies that cross-reacted with the native MSP-2 molecule in an allelic family-specific manner. (2) These mouse antibodies recognized the recombinant proteins in both a variant-specific and a family-specific manner, as shown in inhibition immunoassays. Antibodies raised against the peptide FC27 seemed to be essentially variant-specific, since the soluble form of the S20 antigen (a member of FC27 family) had relatively little inhibitory effect on them. (3) The overall pattern of human IgG antibody responses to MSP-2 in Karitiana Indians, a population continuously exposed to hypoendemic malaria in the Brazilian Amazon Region, differs from that described in hyperendemic areas in Africa and Papua New Guinea in two important features: there was no clear age-dependent increase in the prevalence and mean concentration of specific IgG antibodies, and there was no skewing towards the IgG3 subclass in antibody responses. (4) The relatively poor correlation between concentrations of IgG antibodies that are specific for members of the same allelic family suggests that recognition of MSP-2 peptides by naturally acquired antibodies was largely variant-specific in this population. The potential role of naturally acquired variant-specific antibodies in immune evasion, by selecting mutant parasites carrying insertions or deletions of repeat sequences, is briefly discussed.

Adolescent↗

Duffy blood group genotypes among malaria patients in Rondônia, Western Brazilian Amazon.

We have compared Duffy blood group genotype distribution, as determined by polymerase chain reaction with allele-specific primers, in 68 Plasmodium vivax-infected patients and 59 non-vivax malaria controls from Rondônia, Brazil. Homozygosity for the allele Fy, which abolishes Duffy antigen expression on erythrocytes, was observed in 12% non-vivax controls but in no P. vivax patient. However, no significant association was found between Fy heterozygosity and protection against P. vivax. The Fy x allele, which has recently been associated with very weak erythrocyte expression of Duffy antigen, was not found in local P. vivax patients.

Brazil↗