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Biomedical subjects

R Barthel

Publications and source records attributed to R Barthel.

14 recordsLinked to original sources

Tissue-specific differential antitumour effect of molecular forms of fractalkine in a mouse model of metastatic colon cancer.

BACKGROUND AND AIMS: Fractalkine, a chemokine that presents as both a secreted and a membrane-anchored form, has been described as having tumour-suppressive activities in standard subcutaneous models. Here, we investigate the antitumour effect of fractalkine, in its three molecular forms, in two orthotopic models of metastatic colon cancer (liver and lung) and in the standard subcutaneous model. METHODS: We have developed models of skin tumours, liver and pulmonary metastasis and compared the extent of tumour development between C26 colon cancer cells expressing either the native, the soluble, the membrane-bound fractalkine or none. RESULTS: The native fractalkine exhibits the strongest antitumour effect, reducing the tumour size by 93% in the skin and by 99% in the orthotopic models (p<0.0001). Its overall effect results from a critical balance between the activity of the secreted and the membrane-bound forms, balance that is itself dependent on the target tissue. In the skin, both molecular variants reduce tumour development by 66% (p<0.01). In contrast, the liver and lung metastases are only significantly reduced by the soluble form (by 96%, p<0.002) whereas the membrane-bound variant exerts a barely significant effect in the liver (p = 0.049) and promotes tumour growth in the lungs. Moreover, we show a significant difference in the contribution of the infiltrating leukocytes to the tumour-suppressive activity of fractalkine between the standard and the orthotopic models. CONCLUSIONS: Fractalkine expression by C26 tumour cells drastically reduces their metastatic potential in the two physiological target organs. Both molecular forms contribute to its antitumour potential but exhibit differential effects on tumour development depending on the target tissue.

Animals↗

Epidermal stem cells.

The identification of adult epidermal stem cells that are capable of self-renewal and can reconstitute not only the epidermis but also the cutaneous appendages opens new perspectives for the treatment of a variety of human skin disorders including severe burns, cutaneous cancers, alopecia and acne. However, the implementation and improvement of these novel treatment strategies require a better understanding of the biology of stem cells, in particular regarding their isolation and the maintenance of their unique characteristics in culture. In this review, we summarize the main features of epidermal stem cells and we present the most recent advances in our understanding of the development and maintenance of these cells. In addition, we discuss some of the challenges and the potential clinical applications of epidermal stem cell technology.

Epidermal Cells↗

Stable transfection of the bovine NRAMP1 gene into murine RAW264.7 cells: effect on Brucella abortus survival.

Genetically based natural resistance to brucellosis in cattle provides for novel strategies to control zoonotic diseases. Bovine NRAMP1, the homologue of a murine gene (Bcg), has been identified as a major candidate for controlling the in vivo resistant phenotype. We developed an in vitro model for expression of resistance- and susceptibility-associated alleles of bovine NRAMP1 as stable transgenes under the regulatory control of the bovine NRAMP1 promoter in the murine RAW264.7 macrophage cell line (Bcg(s)) to analyze the regulation of the NRAMP1 gene and its role in macrophage function. We demonstrated that the 5'-flanking region of bovine NRAMP1, despite the lack of TATA and CAAT boxes, has a functional promoter capable of driving the expression of a transgene in murine macrophages. A polymorphism within a microsatellite in the 3' untranslated region critically affects the expression of bovine NRAMP1 and the control of in vitro replication of Brucella abortus but not Salmonella enterica serovar Dublin. We did not observe any differences in the production of NO by resting or gamma interferon (IFN-gamma)- and IFN-gamma-lipopolysaccharide (LPS)-treated transfected cell lines, yet the resistant transfected cell lines produced significantly less NO than other cell lines, following stimulation with LPS at 24 and 48 h.

3' Untranslated Regions↗

Pathologic findings and association of Mycobacterium bovis infection with the bovine NRAMP1 gene in cattle from herds with naturally occurring tuberculosis.

OBJECTIVE: To determine necropsy and Mycobacterium bovis culture results in cattle from herds with tuberculosis, the role of the bovine NRAMP1 gene in resistance and susceptibility to infection with M bovis, and the association between magnitude of the tuberculous lesions and various types of M bovis isolates. ANIMALS: 61 cattle from herds with tuberculosis in Texas and Mexico. PROCEDURE: 61 cattle were evaluated by necropsy; 59 had positive and 2 had negative caudal fold tuberculin intradermal test (CFT) results. Thirty-three cattle with positive CFT results were genotyped to evaluate polymorphism of the 3' untranslated region of the bovine NRAMP1 gene, using single-stranded conformational analysis, 9 were resistant to M bovis with no tuberculous lesions and negative M bovis culture results, and 24 were susceptible with tuberculous lesions and positive M bovis culture results. Isolates of M bovis were analyzed by restriction fragment length polymorphism (RFLP) on the basis of IS6110 sequences and direct-repeat fingerprinting patterns. RESULTS: 21 (35.6%; 21/59) cattle with positive CFT results had tuberculous lesions or positive culture results; in addition, 1 of 2 cattle with negative CFT results had tuberculous lesions and positive culture results. Tuberculous lesions were most common in the thorax (35/63; 55.5%) and lymphoid tissues of the head (10/63; 15.9%). Tuberculous lesions varied from 1 to 11/animal; 8 of 21 (38.1%) had solitary lesions. Associations were not found between resistance or susceptibility to infection with M bovis and polymorphism in the NRAMP1 gene or between the magnitude of the lesions and various RFLP types of M bovis isolates. CONCLUSIONS AND CLINICAL RELEVANCE: The NRAMP1 gene does not determine resistance and susceptibility to infection with M bovis in cattle.

Alleles↗

Rectal stricture in an ostrich (Struthio camelus).

Exploratory celiotomy of an 18-mo-old female ostrich (Struthio camelus) with anorexia, lethargy, and constipation of 5 days' duration showed mesenteric volvulus and a focal narrowing of the rectum approximately 28 cm cranial to the cloaca. The prognosis was poor and the animal was euthanized. Necropsy revealed a fibrinonecrotic proctitis and a 3-cm-long circumferential stricture of the rectum. Histologically, the rectal wall at the stricture was deeply effaced by fibrovascular connective tissue with vascular thrombosis and necrotizing vasculitis, and it resembled the lesions in feeder pigs with fibrinonecrotic colitis.

Animals↗

Ocular Halicephalobus (syn. Micronema) deletrix in a horse.

Ocular contents from a horse with a 4-week history of severe unilateral uveitis were submitted for histopathologic examination. A severe unilateral granulomatous chorioretinitis with intralesional Halicephalobus deletrix was diagnosed. The horse developed progressive neurologic signs several days following the surgery to remove ocular contents and implant a prosthesis and was subsequently euthanatized. A severe multifocal granulomatous encephalitis with intralesional H. deletrix, localized primarily to the optic chiasm, thalamus, and brain stem, was diagnosed from tissues acquired at necropsy. The other eye was not affected. This is the first report of ocular parasitism by H. deletrix and suggests possible systemic dissemination from a primary site in the eye.

Animals↗

[Shute's suture in mediolateral episiotomy. A technique with many advantages (author's transl)].

A comparison of median with mediolateral episiotomy shows that mediolateral episiotomy offers notable advantages resulting naturally from its anatomical course and the possibility of eventual distension. -- The Shute seam is described as a suturing technique in episiotomy still largely unknown in Europe. Apart from easy and rapid suturing and much cleaner wound healing it offers the advantage of significant reduction of pain during childbed with very satisfactory functional and cosmetic results. -- Reduction of wound pain seems to be a decisive factor for the woman in childbed, especially in view of subsequent births, thus making it easier for the obstetrician to obtain the patient's consent for performing episiotomy.

Episiotomy↗

[Transcervical extraamniotic Rivanol instillation as a method of avoiding complications in pregnancy interruption].

The number of abortions performed is steadily increasing. According to information available to date from the Federal Statistics Office in the Federal Republic of Germany, pregnancies are still largely terminated by means of cervical dilatation with Hegar dilatators and subsequent curettage. Almost half of all abortions are performed in young women who have not yet given birth. In a great number of cases these patients have a gracile, rigid cervical os which has to be opened abruptly in a few minutes with Hegar's dilatators, often under asserting quite some force. This can result in lacerations of the cervix, cervical insufficiency, inflammation and cicatrization. The transcervical extraamnial Rivanol instillation seems to be a method for avoiding these early and the serious late complications ensuing. Using this method--an alternative to the Prostaglandine application, with its even more serious secondary effects and contraindications--the highest possible degree of success can be achieved in avoiding cervical injuries and in reducing inflammation in the pelvis minor to a minimum, which could later on lead to sterility.

Abortion, Induced↗

[Studies on mortality in diabetics in a circumscribed region: age and death, length of diabetes and causes of death].

Studies were carried out in regard to the age at death, duration of diabetes mellitus at the time of death and cause of death in an unselected evaluation of the findings in all 1694 diabetics who died in Erfurt and environs over an 11-year period. The The mean age of the patients at the time of death was 70.6 years, with virtually no difference between the sexes. Only six patients died prior to the age of 40. In accordance with the age structure of diabetics in a circumscribed area, the average survival time was 6.5 years. The interval between the first manifestation of the disease and death was 0 to 4 years in 45% of the patients; only every fifth patient survided for 10 or more years. These results are interpreted as being a reflexion of the frequent incidence of preceding or simultaneously-occuring atherosclerosis in these diabetics. Cardiovascular incidents affecting, above all, the coronary and cerebral vessels, account for about 60% of the deaths. Differences between these results and other statistical analyses can be explained on the basis of the unselective nature of the case material in the present study which was, moreover, collected in a defined region over a definite period of time.

Adult↗

Kinetics of recombinational hybrid formation in X-irradiated mammalian cells: a possible first step in the repair of DNA double-strand breaks.

It is known that mammalian cells repair X-ray-induced double-strand breaks (DSB). The mechanism of this repair is, however, as yet unknown but it is thought that the repair may involve recombination between homologous DNA strands. We have investigated the presence and kinetics of occurrence of recombinational molecular intermediates or 'heavy-heavy' (HH) hybrids in DNA of X-irradiated mouse Ehrlich ascites tumour cells unifiliarly substituted with bromodeoxyuridine. Purified DNA from density-labelled cells was analysed using isopyknic CsCl density centrifugation. After rebanding of the high-density material, the relative amount of HH-hybrid material was determined. When the cells were incubated after X-ray exposure, hybrids accumulated with an apparently biphasic kinetic; first a rapid accumulation directly after irradiation followed by a second, more slowly appearing peak. When DSB repair was inhibited by the nucleoside analogue 9-beta-D-arabinofuranosyladenine (ara-A), a powerful DNA polymerase inhibitor, the kinetics of the HH-hybrid formation were similar to those during the incubation after X-irradiation without ara-A. We interpret this as indicating that the first step in repair of DSB i.e. hybrid formation, occurs in the absence of DNA synthesis as predicted by the Resnick model of DSB repair. In an experiment in which the ara-A was washed away from the irradiated cells after 8-h treatment with the drug and replaced by fresh growth medium, so allowing DSB to repair, a similar HH-hybrid kinetic response was found to that occurring directly after irradiation in the absence of ara-A. The reasons for this are not yet clear. In this case, however, the response of the ara-A-treated cells after X-irradiation was much stronger than that in the untreated cells where only approximately 20% of the DSB remained. These kinetic results which show a temporary appearance of HH hybrids, indicate that a net exchange of genetic material does not take place; they therefore lend support to the postulated recombinational model of Resnick in which a temporary exchange between homologous DNA strands takes place during DSB repair.

Animals↗