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  • 1
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Two new experimental approaches were established to analyse the influence of the thymus on tolerance induction to major histocompatibility complex (MHC) antigens: The aim of the first experiment was to perform successful transplantation of adult allogeneic thymus tissue into nude mice, an attempt that has been unsuccessful in the past. Tolerance for the MHC genotype of a prospective thymus graft recipient (A) was induced in mice of strain B by injection of (AxB) splenocytes during the neonatal period. Adult thymic tissue obtained from these allogeneic donors (B) were grafted into the nude mice of strain A. The allogeneic thymus was accepted by the nude mice and immunoreconstitution was achieved. Subsequently the recipients developed tolerance to the MHC antigens of the allogeneic thymus donor as proved by mixed lymphocyte cultures and the acceptance of skin grafts. The second experiment was designed to determine which la-positive thymic compartment participates in confering tolerance to MHC antigens in maturing T lymphocytes. Chimaeric thymus grafts were created by transplantation of neonatal thymus (A) into allogeneic nude mice (B) for a period of 8 weeks. The graft was populated with host bone marrow-derived la antigen-positive cells. The chimaeric thymuses consisting of type A epithelium but populated with both type A and B lymphocytes and non-lymphoid cells (i.e. la-positive maerophages and dendritic cells), were newly transplanted into nude mice of strain A. The engraftment led to immunological reconstitution and the nude mice acquired tolerance to the MHC antigens expressed by the allogeneic ta-positive cells populating the chimaeric graft. Irradiation ofthe chimacric thymus prior to transplantation allowed transplantation of chimaeric thymus devoid of living thymocytes but still populated with functionally intact la-positive non-lymphoid cells. Transplantation of irradiated chimaeric thymuses resulted in immunoreconstitution and induced exactly the same allotolerance pattern as described above. The results demonstrate that not thymus epithelial cells but a bone-marow-derived non-lymphoid thymus cell, most likely the la-antigen-positive thymic macrophage of dendritic cell, is responsible for the induction of tolerance to MHC antigens in developing T lymphocytes.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: When bone marrow transplantation recipients undergo standard pre-transplant immunosuppressive therapy, engraftment failures are significantly more frequent with the use of T-depleted allogeneic donor bone marrow cells than with T cell-containing allogeneic donor bone marrow cells. The relative importance of T versus natural killer (NK) cells in the rejection process of T-depleted donor bone marrow cells remains debatable. Here, NK- and T-deficient mouse mutants were transplanted across the same major histocompatibility complex (MHC) differences with homozygous or heterozygous T-depleted bone marrow cells. Results show that under the experimental conditions described, residual host NK cells are almost exclusively responsible for the increased rejection rate.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Pediatric radiology 21 (1991), S. 236-237 
    ISSN: 1432-1998
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report a female neonate who developed severe septicemia presenting with pneumonia and hepatitis due to an infection with herpes simplex virus type II. In spite of antiviral as well as intensive care therapy, three weeks after admission, extensive hepatic calcification was demonstrable on abdominal radiograph, a sign of severe cellular necrosis. In contrast the pulmonary infiltration recovered completely. The clinical follow up was completed by ultrasound and radiography. The infant died at the age of two months secondary to severe postnecrotic hepatic failure. At autopsy, histological evaluation confirmed the former diagnostic and technical findings; in addition, pulmonary calcifications were detected morphologically which had not been seen on the chest radiograph. The significance of progressive organ calcifications for the prognosis of recovery has been discussed.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1440
    Keywords: Vesico-renal reflux ; Renal parenchymal scar ; Urinary tract infection ; Asymptomatic bacteriuria ; Uroepithelial cell ; Vesico-renaler Reflux ; Nierenparenchymnarbe ; Harnwegsinfektion ; Asymptomatische Bakteriurie ; Uroepithelzelle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung 62 Patienten (14 Knaben, 48 Mädchen), bei denen an insgesamt 85 Niereneinheiten ein vesico-renaler Reflux (Grad 2–4) erfolgreich operiert worden war, wurden im Durchschnitt 9,3 Jahre postoperativ auf das Auftreten von Harnwegsinfektionen (HWI) und von neuen Nierenparenchymnarben (NN) verfolgt. Bei den männlichen Patienten traten postoperativ bis auf einen Knaben keine HWI bzw. NN auf. Ähnliches galt auch für etwa 45% der Mädchen. Beide Gruppen von Patienten wiesen vor Operation hohe Refluxgrade auf. Bei den übrigen Mädchen, deren präoperative Reflux-Grade im Durchschnitt relativ niedrig lagen, traten jedoch postoperativ über Jahre noch HWI auf. NN entwickelten sich vorwiegend in dieser Zeit. Untersuchungen der Fähigkeit von Uroepithelzellen (UEZ), das Bakterienwachstum zu hemmen, zeigten, daß die UEZ dieser Patienten das Bakterienwachstum nicht supprimieren konnten. Somit entsprachen diese Mädchen bezüglich ihrer UEZ-Funktion Patientinnen mit asymptomatischer Bakteriurie. HWI und NN bei Reflux scheinen somit durch unterschiedliche Ursachen ausgelöst zu werden.
    Notes: Summary 62 patients (14 boys, 48 girls) representing 85 refluxive renal units (Grade 2–4) were investigated after successful operation for the development of further urinary tract infections (UTI) and renal scars (RS). The mean follow-up was 9.3 years. With the exception of one boy, none of the male patients developed any UTI or new RS. A similar result was obtained for about 45% of the girls. These two groups of patients presented with high-grade reflux before surgery. The remaining female patients (about 55%), however, presenting with lower-grade reflux before surgical treatment, developed further UTI as well as new RS despite surgical correction of their reflux. Investigations on the capacity of uroepithelial cells (UEC) to suppress bacterial growth revealed a deficient antibacterial effect of UEC in these patients. Such an UEC defect has also been shown in patients with asymptomatic bacteriuria. In conclusion, different reasons seem to be responsible for recurrent UTI and the development of RS in patients with reflux.
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  • 5
    ISSN: 1433-3023
    Keywords: Key words: Bacterial adherence; Intraepithelial calcium flux; Mucosal host defense; PgE2 release
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract: Mucosal epithelial cells contribute significantly to host defense mechanisms. Uroepithelial cells (UEC) from healthy donors suppress bacterial growth in vitro. Bacterial adherence to UEC has been shown to be a prerequisite. Similar results have been shown for buccal epithelial cells (BEC). The host response triggered by the host–parasite interaction seems to involve signal transduction and intracellular activation of second messengers. In this study the intraepithelial calcium flux was analyzed in individual BEC after bacterial contact. BEC were derived from scrapes of the buccal mucosa and labelled with fluo-3 (a calcium indicator). Thereafter the cells were analyzed immediately with a FACscan flowcytometer. The intracellular events were evaluated before and after the addition of viable E. coli bacteria (strain 4389, K1O1H7, pili II pos.). For control, the influence of prostaglandins, histamine, PMA, LPS and opsonized avital E. coli on the epithelial calcium flux was investigated. Additionally, supernatants of BEC-E. coli cocultures were analyzed with respect to their PgE2 content. PgE2 concentrations in supernatants of BEC, cultured alone or together with E. coli, were measured by a commercial PgE2 ELISA kit. The addition of vital E. coli to BEC was promptly answered by a significant intracellular calcium flux. PgE2, histamine and PMA, but not PgF2α, PgE1, LPS and opsonized E. coli, increased intracellular calcium. BEC alone did not release PgE2. After coculture with E. coli increased levels of PgE2 were measured in the supernatants. PgE2 release was still enhanced by coactivation of the BEC with phorbolester (PMA). Our results confirm that calcium flux in mucosal epithelial cells is stimulated by the cell–bacteria contact. We suggest that the increased PgE2 release amplifies the stimulation of intraepithelial second messengers. The resulting cell activation may lead to the secretion of antimicrobial peptides, thereby contributing to the regulation of mucosal host resistance to bacterial infections.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Monatsschrift Kinderheilkunde 145 (1997), S. 347-352 
    ISSN: 1433-0474
    Keywords: Schlüsselwörter Hypoparathyreoidismus ; Innenohrschwerhörigkeit ; Renale Dysplasie ; Key words Hypoparathyroidism ; Deafness ; Renal dysplasia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Three children with primary, nonfamilial hypoparathyreoidism presented with high-grade sensorineural deafness. Based on clinical and molecular evidence, one could be diagnosed as Kearns-Sayre syndrome. The basis of the association in the other cases remains unclear. The combination of symptoms seems to be more frequent than peviously assumed, affecting 3 of 9 children treated at our clinic because of primary, nonfamilial hypoparathyreoidism. Genetically determined dysfunction of cochlear haircell motility and haircell damage as consequence of reduced calcium concentrations in peri- and endolymph are discussed as pathogenetic factors of sensorineural deafness in cases of hypoparathyreoidism. Two of the children showed a marked renal dysplasia. Similar familial cases with associated kidney malformations have been reported in the literatur, indicating the possibiliy of a common cause for hypoparathyreoidism, sensorineural deafness and renal dysplasia. Discussion: As a practical consequence of our experience we recommend laboratory investigations (i. e. parathyreoid hormone) in order to exclude an underlying hypoparathyreoidism in patients with sensorineural deafness. Vice versa, an audiogram should be performed in patients with idiopathic hypoparathyreoidism for early recognition and treatment of associated sensorineural deafness.
    Notes: Zusammenfassung Es werden 3 Kinder mit nicht-familiärem Hypoparathyreoidismus beschrieben, die durch eine hochgradige Hörstörung cochleärer Genese auffielen. Während bei einem der Kinder klinisch und molekulargenetisch ein Kearns-Sayre-Syndrom nachgewiesen werden konnte, bleibt die Ursache des gemeinsamen Auftretens der Störungen bei 2 Kindern ungeklärt. Die Assoziation scheint häufiger als bisher angenommen: sie betrifft 3 der in der Kinderklinik Mainz betreuten 9 Kinder mit primärem Hypoparathyreoidismus. Genetisch determinierte Störungen der Haarzellmotilität der Cochlea sowie Haarzellschädigung als Folge chronisch verringerter Kalziumkonzentrationen in der Peri- und Endolymphe werden als pathogenetische Faktoren der sensorineuralen Hörstörung bei idiopathischem Hypoparathyreoidismus diskutiert. Beim Kearns-Sayre-Syndrom spielt der ATP-Mangel eine besondere Rolle und erklärt möglicherweise die Progredienz der Hörstörung trotz Normalisierung des Serumkalziumspiegels unter der Therapie mit 1,25-Dihydroxycholecalciferol. Bei 2 der 3 Patienten fand sich eine ausgeprägte renale Dysplasie. In der Literatur wurden ähnliche, familiäre Fälle mit assoziierter Nierenfehlbildung beschrieben, die auf eine gemeinsame Ursache von Hypoparathyreoidismus, sensorineuraler Hörstörung und renaler Dysplasie hinweisen. Diskussion: Die beschriebenen Fälle legen die Empfehlung nahe, im Rahmen der Abklärung einer Innenohrschwerhörigkeit einen Hypoparathyreoidismus auszuschließen. Umgekehrt sollte bei allen Patienten mit Hypoparathyreoidismus eine eingehende pädaudiologische Diagnostik zur rechtzeitigen Erfassung und Behandlung einer assoziierten Hörstörung erfolgen.
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  • 7
    ISSN: 1432-198X
    Keywords: Key words: Uroepithelial defense mechanism ; Membranous signal transduction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. It has been shown previously that the interaction between uroepithelial cells (UEC) from healthy donors and adherent Escherichia coli suppresses bacterial growth in vitro. The following study was performed to investigate the nature of membrane signal transduction mechanisms involved in this process. UEC/E. coli cocultures were established in the presence of substances known to modulate transmembranous signals. Inhibition of calcium flux, either by calcium channel-blocking substances or by a calmodulin antagonist, depressed the antibacterial UEC function of “healthy” UEC. In contrast, receptor/ligand-induced stimulation of G-proteins, activation of the adenylate cyclase, and the increase of intracellular cyclic AMP levels by cytoplasmatic phosphodiesterase did not increase the antibacterial capacity of healthy UEC. However, the antibacterial function of defense-deficient UEC from patients with recurrent idiopathic urinary tract infection could be reconstituted by this treatment to almost normal levels. In conclusion, the antibacterial UEC defense function is activated by transmembranous signals from bacteria attached to the host cell surface. Activation involves the adenylate cyclase pathway. Activation of the phosphoinositol pathway may contribute to intracellular calcium fluxes.
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  • 8
    ISSN: 1432-198X
    Keywords: Key words: Urinary tract infection ; Bacterial adhesion ; Uroepithelial defense mechanism ; Ligand-receptor interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Uroepithelial defense has been suggested to contribute to the local host resistance against ascending urinary tract infection. The cellular mechanism, however, is not known. In this study, bacterial growth was measured under the direct and indirect influence of uroepithelial cells. To study if a specific ligand-receptor interaction is required for uroepithelial cell (UEC) activation, isogenic Escherichia coli mutants expressing either mannose-sensitive, mannose-resistant (p), or mannose resistant (s) pili were tested for their capacity to induce the UEC defense mechanism. The antibacterial effect of UEC was abolished either by performing coculture in chambers with a fluid-permeable membrane which separates UEC from bacteria or by inhibiting membrane contact using the antiadherence factor pentosane polysulfate. No difference between the various types of pili could be shown. All E. coli strains adhered comparably to the UEC and were subsequently suppressed in their growth. Even a “naked” mutant without expression of common pili showed a similar behavior. In conclusion, bacterial growth suppression depends on direct contact between the UEC and bacteria, but is independent of common pili expressed on E. coli.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    European journal of pediatrics 145 (1986), S. 330-336 
    ISSN: 1432-1076
    Keywords: UTI ; Renal scars ; Virulence factors ; Host factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-1076
    Keywords: Urinary tract infection ; Bladder defence mechanism ; Uroepithelial cells ; Buccal epithelial cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of buccal epithelial cells (BEC) on bacterial growth was investigated in healthy subjects as well as in patients with recurrent urinary tract infections (UTI) and compared to the antibacterial capacity of uroepithelial cells (UEC) of the same individuals. Epithelial cells were obtained from the following groups: healthy female controls; females without further UTI after reflux operation; females with asymptomatic bacteriuria (ABU); females with further UTI despite successful reflux operation; and patients with meningomyelocele (MMC) and recurrent UTI due to significant residual urinary volume. Cocultivation of Escherichia coli with BEC as well as UEC from healthy females or patients with MMC resulted in significant suppression of bacterial growth. However, neither type of epithelial cell showed an antibacterial effect when they were obtained from patients with recurrent UTI in the absence of urological abnormalities (ABU patients; reflux-corrected patients with further UTI). From these results it is concluded that a generalised epithelial defence defect is one important pathogeneic factor for recurrent idiopathic UTI.
    Type of Medium: Electronic Resource
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