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Biomedical subjects

B Christen

Publications and source records attributed to B Christen.

At least 19 recordsLinked to original sources
PubMed2004

Cellular and molecular mechanisms of regeneration in Xenopus.

We have employed transgenic methods combined with embryonic grafting to analyse the mechanisms of regeneration in Xenopus tadpoles. The Xenopus tadpole tail contains a spinal cord, notochord and segmented muscles, and all tissues are replaced when the tail regenerates after amputation. We show that there is a refractory period of very low regenerative ability in the early tadpole stage. Tracing of cell lineage with the use of single tissue transgenic grafts labelled with green fluorescent protein (GFP) shows that there is no de-differentiation and no metaplasia during regeneration. The spinal cord, notochord and muscle all regenerate from the corresponding tissue in the stump; in the case of the muscle the satellite cells provide the material for regeneration. By using constitutive or dominant negative gene products, induced under the control of a heat shock promoter, we show that the bone morphogenetic protein (BMP) and Notch signalling pathways are both essential for regeneration. BMP is upstream of Notch and has an independent effect on regeneration of muscle. The Xenopus limb bud will regenerate completely at the early stages but regenerative ability falls during digit differentiation. We have developed a procedure for making tadpoles in which one hindlimb is transgenic and the remainder wild-type. This has been used to introduce various gene products expected to prolong the period of regenerative capacity, but none has so far been successful.

Animals↗
PubMed2001

Nerve-independence of limb regeneration in larval Xenopus laevis is correlated to the level of fgf-2 mRNA expression in limb tissues.

In both larval and adult urodele amphibians, limb blastema formation requires the presence of an adequate nerve supply. In previous research, we demonstrated that the hindlimb of early Xenopus laevis larvae formed a regeneration blastema even when denervated, while the denervated limb of late larvae did not. We hypothesized that the nerve-independence was due to the autonomous synthesis of a mitogenic neurotrophic-like factor by undifferentiated limb bud cells. In this paper, we demonstrate that fgf-2 mRNA is present in larval limb tissues and that its level is correlated to the extent of mesenchymal cells populating the limb: in early limbs, fgf-2 mRNA is present at high levels all over the limb, while, in late limbs, the fgf-2 expression is low and detectable only in the distal autopodium. After denervation, fgf-2 mRNA synthesis increases in amputated early limbs but not in amputated late limbs. The implantation of anti-FGF-2 beads into amputated early limbs hardly lowers the mitotic activity of blastema cells. However, FGF-2 beads implanted into the blastema of late limbs prevent the denervation-induced inhibition of mitosis and oppose blastema regression. Our data indicate that FGF-2 is a good candidate for the endogenous mitogenic factor responsible for blastema formation and growth in amputated and denervated early limbs. However, in amputated late limbs, the very limited fgf-2 expression is not sufficient to promote blastema formation in the absence of nerves.

Animals↗
PubMed1999

Spatial response to fibroblast growth factor signalling in Xenopus embryos.

We have examined the spatial pattern of activation of the extracellular signal-regulated protein kinase (ERK) during Xenopus development, and show that it closely resembles the expression of various fibroblast growth factors (FGFs). Until the tailbud stage of development, all ERK activation domains are sensitive to the dominant negative FGF receptor, showing that activation is generated by endogenous FGF signalling. ERK is not activated by application of other growth factors like BMP4 or activin, nor is endogenous activation blocked by the respective dominant negative receptors. This shows that various domains of FGF expression, including the periblastoporal region and the midbrain-hindbrain boundary, are also sites of FGF signalling in vivo. Wounding induces a transient (<60 minutes) activation of ERK which is not significantly reduced by the dominant negative FGF receptor. An artificial FGF source, created by injection of eFGF mRNA into cleavage stage embryos, provokes ERK activation outside of its injection site over a range of several cell diameters. The range and extent of ERK activation outside the source region is unchanged by co-injection of a dominant negative form of Ras, which blocks ERK-activation within the source. This suggests that FGF protein can diffuse over several cell diameters.

Actins↗
PubMed1998

dMi-2, a hunchback-interacting protein that functions in polycomb repression.

Early in Drosophila embryogenesis, gap gene products directly repress transcription of homeotic (HOX) genes and thereby delimit HOX expression domains. Subsequently, Polycomb-group proteins maintain this repression. Currently, there is no known molecular link between gap and Polycomb-group proteins. Here, dMi-2 is identified as a protein that binds to a domain in the gap protein Hunchback that is specifically required for the repression of HOX genes. Genetic analyses show that dMi-2 participates in both Hunchback and Polycomb repression in vivo. Hence, recruitment of dMi-2 may serve as a link between repression of HOX genes by Hunchback and Polycomb proteins.

Adenosine Triphosphatases↗
PubMed1998

Chitosan-EDTA conjugate: a novel polymer for topical gels.

A recently developed chitosan-EDTA conjugate, neutralized with sodium hydroxide (NaChito-EDTA), has been tested for possible topical use. The technical properties and microbial stability of NaChito-EDTA have been compared with those of carmellose sodium (NaCMC), hydroxypropylmethylcellulose (HPMC), sodium polycarbophil (NaPCP) and sodium carbopol 980 (NaC980), well established gelatinizing agents. NaChito-EDTA forms stable, colourless, completely transparent hydrogels at a polymer concentration of 0.5%. Of the polymers tested the novel polymer had the lowest incompatibility with multivalent cations and with ethanol, and much the best swelling properties. After 28 days of incubation at room temperature the rates of growth of the complete bacterial spectrum occurring in demineralized water and of Escherichia coli, serving as model strain representative of gram-negative bacteria, were at least 2 log and 5.7 log, respectively, lower in NaChito-EDTA gels than in the other hydrogels. This antimicrobial activity of NaChito-EDTA can be explained by its highest binding affinity towards magnesium, which stabilizes the outer membrane of gram-negative bacteria. However, this antimicrobial effect is insufficient to guarantee microbial stability. Further results showed that the antimicrobially acting polypeptide nisin can be recommended as an alternative novel preservative for NaChito-EDTA gels, because its antimicrobial spectrum could also be increased towards gram-negative bacteria in combination with chelating excipients. NaChito-EDTA seems, therefore, to be a promising novel polymer for topically-used gels, with advantages over well established gelatinizing agents.

Administration, Topical↗
PubMed1997

FGF-8 is associated with anteroposterior patterning and limb regeneration in Xenopus.

FGF-8 has attracted attention particularly because of its importance for limb development in the chick and mouse, although it also has a number of earlier expression domains in these species. We have now cloned an FGF-8 homologue from Xenopus in which it is easier to do functional studies on early development. There is no maternal expression, while zygotic expression is highest in the gastrula and neurula stages. XFGF-8 is expressed as a ring around the blastopore and subsequently in the tail bud. There are several domains in the head including the hatching gland, the branchial clefts, and the midbrain-hindbrain border. At later stages there is a prominent band of expression in the limb bud epidermis. Although there is no morphological apical ridge, this band of expression suggests that the Xenopus limb bud contains a cryptic region with a similar ability to stimulate mesenchymal outgrowth. The mesoderm-inducing activity of XFGF-8 is somewhat lower than that of other FGFs, while the posteriorizing activity is similar. These differences are probably due to the different receptor specificity. The posterior expression and high posteriorizing activity suggest that XFGF-8 contributes to the patterning of the anterior-posterior axis by FGF family members during gastrulation. In contrast to the amniotes, Xenopus limb buds can regenerate following damage. We show that regeneration is correlated with the reexpression of XFGF-8 in the distal epidermis, suggesting that this ability is critical for successful limb regeneration.

Amino Acid Sequence↗
PubMed1994

Imaginal disc silencers from Ultrabithorax: evidence for Polycomb response elements.

Silencers from the Drosophila homeotic gene Ultrabithorax (Ubx) require hunchback (hb) and Polycomb (Pc) to suppress the activity of embryonic enhancers outside the Ubx domain. Embryonic silencing is initiated by hb protein which binds to the silencers to repress Ubx, thereby defining the Ubx domain. Here, we study silencing during subsequent development by examining expression patterns in imaginal discs conferred by individual Ubx fragments and pair-wise combinations thereof. We find that fragments which mediate silencing in anterior regions of imaginal discs contain embryonic silencers and hb target sites. One exception to this is a fragment called BXD which is not under hb control itself, but whose silencing activity depends on combination with fragments containing hb protein binding sites. Since silencing by BXD also requires Pc function, this suggests that BXD contains target sites for Pc or for Pc-like proteins. We propose that stable silencing of Ubx is achieved through cooperation between hb and Pc target sites.

Animals↗
PubMed1993

[Antibiotic-resistant pneumonia].

A 77-year-old lady with malaise, cough, weight loss, an elevated ESR and bilateral patchy infiltrates on the chest X-ray is described. The symptoms progressed inspite of antibiotic treatment. On the basis of clinical findings, transbronchial biopsy, bronchoalveolar lavage and lung function tests the diagnosis of a bronchiolitis obliterans, organizing pneumonia (BOOP) was established. The clinicopathological entity of BOOP, its differential diagnosis and treatment are discussed.

Aged↗
PubMed1992

[Bronchobiliary fistula in carcinoma of the hepatic duct bifurcation].

Carcinoma of the hepatic duct bifurcation was diagnosed in a 67-year-old women with obstructive jaundice. As metastatic spread could not be demonstrated the carcinoma was removed with a view of achieving a cure (hemihepatectomy, resection of the hepatic duct and the bifurcation, cholecystectomy and hepatojejunostomy). Histological examination indicated adenocarcinoma of the biliary tract. Seven months postoperatively the patient was found to be cachectic and cough up greenish liquid sputum. Bilirubin concentration in sputum was 500 mumol/l. There was no jaundice and total bilirubin concentration was 33 mumol/l. Alkaline phosphatase was 508 U/l, but GOT and GPT were normal (23 U/l and 21 U/l). Computed tomography confirmed the clinical diagnosis of a biliobronchial fistula. The patient died 9 days after renewed hospitalization of tumour cachexia. The biliobronchial fistula was found at necropsy.

Adenocarcinoma↗
PubMed1992

A cis-element mediating Ultrabithorax autoregulation in the central nervous system.

We dissected an upstream control region (a BXD fragment) from the homeotic gene Ultrabithorax (Ubx) of Drosophila which confers a Ubx-like expression pattern in the embryonic ectoderm. We found several distinct enhancer elements spread through the whole BXD fragment each of which is active in transformed embryos, mediating a different pattern of beta-galactosidase expression in the ventral nerve cord. The strongest of these patterns mimics Ubx expression within the Ubx domain. This pattern is strictly dependent on Ubx function. Thus, the BXD control region contains a Ubx response element, suggesting that positive autoregulation of Ubx may occur in the central nervous system of the developing embryo.

Animals↗
PubMed1992

Serodiagnosis of Lyme borreliosis by western immunoblot: reactivity of various significant antibodies against Borrelia burgdorferi.

The significance of various antibodies against Borrelia burgdorferi was studied by Western blot (immunoblot) by using 578 human serum samples. The proteins regularly detected by using samples from patients with Lyme borreliosis were those with bands with molecular masses of 94, 83, 75, 66, 60, 55, 46, 41, 39, 34, 31, 29, 22, and 17 kDa. The detectable frequencies of most of these proteins appeared to be significantly different between the sera from patients with Lyme borreliosis and those from normal control individuals as well as from the group with syphilis. The 39-kDa protein band recognized by polyvalent antibody was found to be the most significant marker for Lyme borreliosis. Furthermore, an anti-39-kDa immunoglobulin M response was detected in the samples from patients with early-stage Lyme borreliosis. Results from the use of monoclonal antibodies and patient sera revealed that the 39- and 41-kDa proteins may be structurally related but are immunologically distinct antigens. The significance of antibody reactivities to the 41-, 94-, 22-, 31-, and 34-kDa protein bands is also discussed.

Antibodies, Bacterial↗
PubMed1992

Fractures associated with patellar ligament grafts in cruciate ligament surgery.

We reviewed retrospectively 490 patellar ligament reconstructions for cruciate ligament injuries performed from 1980 to 1990. There were six cases of patellar splitting and three displaced patellar fractures in donor knees. The fissure fractures all occurred during the removal of the patellar bone block. The displaced fractures were sustained during early rehabilitation, and in two of the three patients, involved the normal contralateral knee. The major reasons for this complication were imprecise saw cuts, spreading osteotomies, and the use of a too large patellar bone block. When a trapezoidal bone block is used to self-lock in the femoral tunnel, this should preferably be taken from the tibia. Special care is needed in rehabilitation when the graft has been taken from the contralateral knee.

Adult↗
PubMed1991

Ligand-independent activation of the sevenless receptor tyrosine kinase changes the fate of cells in the developing Drosophila eye.

Cell fate in the developing eye is determined by a cascade of inductive interactions. In this process, the sevenless protein--a receptor tyrosine kinase--is required for the specification of the R7 photoreceptor cell fate. We have constructed a gain-of-function sevenless mutation (SevS11) by overexpressing a truncated sevenless protein in the cells where sevenless is normally expressed. In SevS11 mutant flies, all sevenless-expressing cells initiate neural development. This results in the formation of multiple R7-like photoreceptors per ommatidium. Therefore, sevenless activity appears to be necessary and sufficient for the determination of R7 cell fate. These results illustrate the central role receptor tyrosine kinases can play in the specification of cell fate during development.

Animals↗
PubMed1987

Immunohistochemistry in the diagnosis of malignant mesothelioma.

The histological diagnosis of malignant mesothelioma of the pleura, especially the distinction from peripheral adenocarcinoma of the lung, may be difficult. The immunohistochemical reports previously published on this subject show diverging results mainly because a variety of antibodies and staining techniques have been used by the different authors. To obtain comparable and reproducible results standard techniques and commercialized antibodies should be applied in routine pathology. In order to investigate the value of immunohistochemistry for the separation of the two entities formalin fixed and paraffin embedded blocks of 47 mesotheliomas and 22 adenocarcinomas were investigated with the PAP technique and commercially available antibodies to carcino-embryonic antigen (CEA), keratin, vimentin, epithelial membrane antigen (EMA), pregnancy specific antigen (SP1), S-100 protein and monoclonal antibody lu-5 (mAB lu-5). CEA positivity was found in all 22 adenocarcinomas examined, but only 2/47 (4%) of all mesotheliomas showed a positive result. SP1 was positive in 13/22 (59%) of the adenocarcinomas, whereas only 3/47 (6%) mesotheliomas were positive for this marker. No significant difference in the rate of positive cases in the adenocarcinoma and mesothelioma group could be found with the other above mentioned antigens. The results of our study indicate that especially CEA, but also SP1 are valuable markers in the diagnosis of malignant mesothelioma.

Adenocarcinoma↗