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B Hausmann

Publications and source records attributed to B Hausmann.

At least 37 records · Page 2Linked to original sources

Regeneration of axons from the adult rat optic nerve: influence of fetal brain grafts, laminin, and artificial basement membrane.

After transection of the optic nerve of adult rats, most of the axons in the proximal stump die and the surviving ones are unable to regenerate into the distal optic nerve. Since the fetal brain has an inherent capacity to regenerate axons, we investigated whether fetal (E16) target regions of optic axons (thalamus and tectum) transplanted to the completely transected optic nerve of adult rats would promote axon regeneration. In control operated rats, axon growth beyond the site of transection was restricted to a few fibers that grew irregularly within the connective tissue scar. By contrast, in grafted animals directed outgrowth of optic axons toward the transplant started at 6 days postoperation (p.o.) and reached its maximum 15 days p.o. and later, when numerous single optic fibers and small axon fascicles had grown toward and into the graft, where they formed arborizations and terminal varicosities. Regenerating optic axons were further advanced than GFAP-positive strands of astroglia that emanated from the proximal optic nerve stump. Laminin immunoreactivity appeared at 6 days p.o. in the zone of reactive astroglia in the terminal part of the optic nerve stump. Later it showed a distribution complementary to the pattern of GFAP immunoreactivity, which it seemd to circumscribe. There was no unequivocal codistribution of laminin immunoreactivity with regenerating axons. In further experiments, target regions from different ontogenetic stages (E14 to neonate and adult) and nontarget regions (E16, cerebral cortex or spinal cord) were grafted to the optic nerve stump. With the exception of the adult grafts, all transplants had effects on axon regeneration comparable to those of E16 target regions. In order to test the effects of extracellular matrix molecules on axon regeneration, a basement membrane gel reconstituted from individual components of the Engelbreth-Holm-Sarcoma (EHS) sarcoma was implanted between proximal and distal optic nerve stumps. No axons were induced to regenerate by this matrix. Likewise, laminin adsorbed to nitrocellulose paper and implanted at the lesion site did not stimulate axon growth from the proximal optic nerve stump. These results indicate that fetal brain is able to induce and direct regrowth of axons from the optic nerve toward the graft across a substrate that is not composed of astroglia or basement membrane components like laminin. The directed growth of axons in the absence of a preformed substrate implies a chemotactic growth response along a concentration gradient mediated by neurotropic molecules released from the graft.

Animals↗

Fetal brain grafts rescue adult retinal ganglion cells from axotomy-induced cell death.

After intraorbital transection of the optic nerve of adult rats, 90% of the retinal ganglion cells die within 30 days. Since fetal brain extracts and cocultured fetal target regions support the survival of retinal ganglion cells in vitro (Nurcombe and Bennett: Exp. Brain Res. 44: 249-258, '81; McCaffery et al.: Exp. Brain Res. 48: 377-386, '82; Armson and Bennett: Neurosci. Lett. 38: 181-186, '83) we investigated whether cell death in the adult retina could be prevented by transplanting fetal (E16) thalamus and tectum to the proximal stump of the optic nerve of adult rats that was completely transected 2-3 mm behind the optic disc. Unoperated eyes contained 119,973 (+/- 939, SEM) retinal ganglion cells, estimated from axon counts of the intact optic nerve. Of these, 11,601 (+/- 1,857) remained in control operated eyes at 30 days postoperation while in the eyes of grafted rats, 35,086 (+/- 2,278) retinal ganglion cells were counted. Thus, 23,485 (= 22% of those normally dying after transection of the optic nerve) ganglion cells were rescued by the fetal grafts from cell death normally following axotomy. These results indicate that fetal target regions of retinal ganglion cells contain and/or produce neurotrophic molecules that promote the survival of adult axotomized retinal ganglion cells.

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Induction of an immune response to a self antigen.

The question has been addressed whether the endogenous B cell population of a mouse can be induced to secrete antibodies specific for a self antigen present in serum. The antigen studied was the fifth component of mouse complement (C5). Nude BALB/c mice which are C5 sufficient were used as a source of potentially C5-reactive B cells and endogenous serum C5 provided the antigenic stimulus. We purposely avoided immunization with C5 in adjuvant. T cells from C5-deficient mice which lack this component in serum and are therefore not tolerant of C5 were injected into nude mice as a source of T cell help for anti-C5 reactive B cells. Control groups received T cells from C5-sufficient euthymic donors, which are tolerant of C5. Initiation of a response to C5 was monitored by testing the hemolytic function of serum. Reduction of C5-dependent hemolysis was observed in sera of mice which had received T cells from C5-deficient donors. Recipients of T cells from C5-sufficient donors maintained normal hemolytic complement levels throughout the test period of 45 days. Reduction of functional complement levels correlated with the presence of immune complexes of anti-C5/C5. C5-specific antibodies were mainly IgG1 and carried the IgG1 allotype of BALB/c providing unequivocal evidence that they were derived from the endogenous B cell population of the C5-sufficient host.

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Fibroblast growth factors promote the survival of adult rat retinal ganglion cells after transection of the optic nerve.

Basic and acidic fibroblast growth factors (FGF) were implanted next to the proximal stump of the transected optic nerve of adult rats, in order to assess whether these molecules have neurotrophic activity in vivo. Of the 119,973 +/- 2484 (S.E.M.) retinal ganglion cells present in retinae of unoperated control rats, 11,375 +/- 2413 (S.E.M.) remained at 30 days after transection of the optic nerve in control operated rats. After implantation of gel foam soaked in basic FGF, the number of retinal ganglion cells surviving at 30 days after axotomy tripled (36,387 +/- 3270 (S.E.M.], after acidic FGF, it increased almost 4-fold (40,916 +/- 5405 (S.E.M.]. These results indicate that FGF has neurotrophic activity in the adult central nervous system, and that this molecule is able to rescue adult retinal ganglion cells from axotomy induced cell death. It remains to be shown whether FGF acts directly on retinal ganglion cells or indirectly via glial cells or other cells.

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Mta, the maternally transmitted antigen, is determined jointly by the chromosomal Hmt and the extrachromosomal Mtf genes.

Mus spretus from four stocks, originating in Spain, Portugal, and Morocco, were tested for the maternally transmitted antigen, Mta. All expressed a variant form not found in other species of mice. Analysis of appropriate crosses with inbred mice showed that the spretus form of Mta is determined by a new allele, c, of the Hmt gene. The Hmtc allele has been isolated in coupling with four different H-2 haplotypes. It is possible to raise CTL specific for the spretus form of Mta. The maternally transmitted factor, Mtf alpha s, of spretus mice determines, in conjunction with the Hmta allele of C57BL/6, an Mta that is indistinguishable from the common form found in C57BL/6 and most other inbred mice. Our experiments show that the specificity of the cell surface antigen Mta is governed jointly by the cytoplasmic gene Mtf and the chromosomal gene Hmt. We propose that Hmt encodes a class I histocompatibility antigen that acts as a restricting element for the Mtf gene product, thus meeting the requirements of T killer cell recognition.

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Cerebellar external granule cells are attached to the basal lamina from the onset of migration up to the end of their proliferative activity.

The development of cerebellar external granule cells in rats was studied from the time of demarcation of the cerebellar anlage on embryonal day 12 up to the time of their disappearance on postnatal day 20. Two types of cells were found. The first was orientated tangentially to the cerebellar surface and was characterized by a persistent contact to the basal lamina via an external process, with a lamellopodial tip and a cytoskeleton characteristic for migratory cells, and a retracting internal process featuring a single cilium. This cell type was the first to appear on embryonal day 14 in the caudolateral angle of the cerebellar anlage and, later, spread over the whole cerebellar surface. It disappeared after the external granular layer was completely expanded over the cerebellum. The second cell type appeared for the first time on embryonal day 16 in the caudal part of the cerebellar anlage and disappeared on postnatal day 20. It was orientated radially and also had contact with the basal lamina either with its cell body or with one or two short, radial processes, whose morphology differed from that of the external process of tangential cells by the absence of a lamellopodium and a prominent cytoskeleton. After postnatal day 17 contacts of external granule cells with the basal lamina decreased rapidly in length and number and were absent on postnatal day 20. We interpret these findings to indicate that tangential external granule cells are migrating before taking on a radial orientation characteristic for the mitotic cycle of proliferating external granule cells. In the light of increasing evidence implicating extracellular matrix in various developmental events of the nervous system we propose that the basal lamina of the cerebellum may be used as substrate and guidance structure by migrating external granule cells, and, furthermore, that the persistent contact with the basal lamina may mediate stimuli maintaining external granule cells in a proliferative state.

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Derivation of cerebellar Golgi neurons from the external granular layer: evidence from explantation of external granule cells in vivo.

The present report provides evidence to challenge the traditional view that cerebellar Golgi cells are derived from the ventricular neuroepithelium, postulating instead that they originate from external granule cells. Supporting evidence for this assertion comes from three sources: 1) Typical Golgi cells are found in ectopic granule cell colonies, both outside the cerebellum (in the subarachnoid space) and also within the cerebellar cortex between fused folia. Because ectopic granule cell colonies are derived from external granule cells, which become displaced after treatment with 6-hydroxydopamine (6-OHDA), it was assumed that the ectopic Golgi cells also stem from such displaced external granule cells. 2) In order to demonstrate that Golgi cell precursors migrate from the external granular layer into the Purkinje cell plate, the development of the cerebellar cortex was studied over the period of Golgi cell genesis. On E19 the external granular layer in the rat is subdivided into an outer proliferative and an inner subproliferative zone. At the inner margin of the external granular layer, and in the marginal zone, radially oriented, darkly staining cells are present that exhibit all the characteristics of migrating neurons possessing a leading process oriented toward the Purkinje cell plate, a somatic cilium, and a close association with radial glia fibers. In later stages, these cells are also found deep to the Purkinje cell plate. Because Golgi cells arise during the period between E19 and postnatal day 2 in the rat (Altman and Bayer, '77, '78) and as the basket cells, the first neurons of proven origin from the external granular layer, are not produced before the second postnatal day (Altman, '72), the earlier migrating neurons are presumed to be Golgi cells. 3) Available data from cell kinetic 3H-thymidine studies show that there is no unequivocal evidence for Golgi cell genesis from the ventricular neuroepithelium, because, at the time of Golgi cell birth, ventricular and external granular stem cell populations are proliferating, and with the present methods it is not possible to decide which of these are the precursors of Golgi cells. Thus, taken together, the findings of this study show that Golgi cells are more likely to arise from the external granular layer than from the ventricular neuroepithelium. This concept would unify cerebellar histogenesis by proposing that projection neurons arise from the ventricular neuroepithelium, whereas all interneurons of the cerebellar cortex are descendants of the external granular layer.

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Shaving of the lumbar disk space--a new technique in lumbar nucleotomy.

A complete curettage of the intervertebral space using the common surgical instruments (forceps, sharp spoons) is not possible during nucleotomy because of the anatomic site and the shape of the instruments. An alternative technique--called "shaving"--is described, which enables a faster, more effective, and less traumatizing removal of free-floating, pulpy residue in the intervertebral space.

Humans↗

Nucleoscope. Instrumentarium for endoscopy of the intervertebral disc space.

Basing on preliminary endoscopic examinations to present the intervertebral disc interspace using a common arthroscope in operations performed for lumbar disc prolapses, a special endoscopic instrumentarium (nucleoscope Hausmann-Forst) was developed allowing detailed and riskless views into the intervertebral disc interspace.

Arthroscopes↗

Cytoplasmic inheritance of a cell surface antigen in the mouse.

Mta is a cell surface antigen of the mouse and serves as a target for specific T killer lymphocytes. Using a killer cell assay, the antigen has been found in 72 strains of laboratory mice and, with one exception, in all tested samples of mice caught in the wild or bred from such, including Mus molossinus, Mus castaneus and Mus spretus. Five strains of rats, non-inbred NMRI mice, most substrains of NZB mice and the closely related strain NZO are negative for Mta. In reciprocal F1 crosses between several Mta+ and two Mta- strains, the antigen is maternally transmitted; that is, Mta+ females bear only positive offspring, whereas Mta- females bear only negative offspring, regardless of the genotype of the male. Since 34 foster-nursed mice had the Mta type of their genetic mothers, the factor that determines expression of Mta must be transmitted before birth and not via the milk. The cytoplasmic genes of Mta+ strains have been combined with the chromosomal genes of Mta- strains, and vice versa, by repeated backcrossing. All progeny retained the Mta type of their maternal lines. Thus, the Mta type is determined solely by maternal inheritance and is not influenced by chromosomal genes. We found no evidence of incompatibility between the cytoplasmic factors and nuclear genes of Mta- and Mta+ strains.

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Polymorphism of a Qa-1-associated antigen defined by cytotoxic T cells. I. Qed-1a and Qed-1d.

Tlad mice have a distinct Qed-1 allele, Qed-ld. Its product is detected by cytotoxic T cells raised in C57BL/6 (H-2b, Tlab) mice against cells from a new recombinant, B6-TL.123+ (H-2b, Tlad/b). Qed-1d is also found on cells from B10.M, A.CA and B10.STC90 mice. It cross-reacts weakly with Qed-1b (C57BL/6 x BALB/c)F1 anti-B10.A(5R) effectors discriminate Qed-1a and Qed-1d, while C3H/HeJ anti-B10.BR effectors cross-react extensively. CB6F1 anti-5R effector cells also discriminate between the Qed-1 antigens of B6-Tlaa (H-2b, Tlaa) and those of B10.BR and other H-2k, Tlaa strains.

Animals↗

Qed-1--a target for unrestricted killing by T cells.

Two prototype target determinants for unrestricted killing by T cells are defined: Qed-1a, detected on B6.Tlaa targets by C3H/HeJ lymphocytes primed in vivo and restimulated in vitro by B10.BR spleen cells; and Qed-1b, detected on C57BL/6J lymphocytes by B10.BR anti-C3H/HeJ effector cells generated in the same manner. Other mouse strains can be typed for Qed-1 by the ability of their lymphocytes to inhibit one of these lytic reactions. Of 55 inbred strains, 52 expressed either Qed-1a or Qed-1b, which thus behaved as products of alleles of a single locus, Qed-1. The remaining three strains, all H-2r, did not compete against specific lysis of Qed-1a, but inhibited Qed-1b-specific lysis only in part; it is proposed that these strains carry a third allele or haploype, Qed-1c. The Qed-1 locus was mapped distal to Qa-2. Qed-1b was found on both normal and mitogen-activated lymphocytes and did not appear confined to any lymphoid subpopulation. Cytotoxic responses, not restricted by H-2 and specific for antigens controlled by the Tla region, could be induced in several combinations of H-2-identical strains differing at Qed-1. Cells of some strains, like B10.BR, NZB, and SWR, responded directly in culture, even without priming in vivo.

Alleles↗