Über funktionelle Unterschiede zwischen Dünn-und Dickdarm—dargestellt an den verschiedenen Reaktionen der Darmschleimhaut bei Angebot von Lösungen nicht penetrabler Solute und steigender Osmolarität

Zusammenfassung Bei Instillation von Mannitlösungen steigender Osmolarität in durchblutete, in situ belassene Jejunum- und Colonschlingen von Ratten reagieren beide Darmabschnitte unterschiedlich.Während die durch Enterosorption binnen 30 min in das Jejunum gelangte Flüssigkeitsmenge 250% des Instillats ausmacht, beträgt der analoge Wert beim Colon nur 100%. Die enterosorbierten Mengen an Na⁺, Cl^– und Urea sind im Jejunum wesentlich größer als im Colon, da nicht nur die enterosorbierte Flüssigkeitsmenge größer ist, sondern weil auch die intraintestinalen Konzentrationen höher liegen.Zwischen den Ca⁺⁺-Konzentrationen im Jejunum und Colon bestehen keine Unterschiede, die K⁺-Konzentration ist im Colon höher. Bei Berücksichtigung der Wasserbewegungen ist die enterosorbierte Ca⁺⁺-Menge im Jejunum, die K⁺-Menge dagegen im Colon größer.Während der Versuchszeit — 30 min — erfolgt im Jejunum ein osmolarer Konzentrationsausgleich aller Lösungen mit dem Plasma, deren Konzentration kleiner als die 1,66 fache Blutisotonie ist. Im Colon stellt sich dieser Ausgleich auch für eine Lösung von 1,33 facher Blutisotonie nicht mehr ein.Die Colonschleimhaut verhält sich demnach so, als ob hier die Exsorption von Wasser, Na⁺, Cl^–, Ca⁺⁺ und Urea wesentlich stärker behindert wäre als die durch die Schleimhaut des Jejunums.Instillation großer Volumina stark hypertoner (ca. 2000 mOsmol/l) Lösungen, deren Solute nur schwer absorbiert werden können, führen zu einem so großen Einstrom von Blut- und Körperflüssigkeit in den Intestinaltrakt, daß Ratten in schwerer Exsiccose sterben. Dabei steigt der Anteil von Zellen am Blutvolumen von 48% auf 68% der Wassergehalt der geprüften Gewebe — quergestreifte und Herzmuskulatur, Gehirn — sinkt ab.     

Unterschiedliche Flüssigkeits- und Substanzbewegungen durch die Mucosa der verschiedenen Abschnitte des Intestinaltraktes beim Kaninchen

Zusammenfassung Die Schleimhaut des Duodenums beim Kaninchen sezerniert eine blutisotone Flüssigkeit, deren Hauptcharakteristikum ihr HCO₃ ^–-Gehalt von fast 100 mMol/l ist. Auf die Instillation einer Lösung, die wie das duodenale Sekret zusammengesetzt ist, reagiert das Jejunum mit einer isotonen Absorption bei nur geringfügigen Konzentrationsänderungen der Konstituenten der Instillationslösung. Das Ileum reagiert analog dem Jejunum, nur sind die Absorptionsraten für Flüssigkeit und die geprüften Solute größer als im Jejunum. Im Colon kommt es zu einer Enterosorption von Flüssigkeit mit teilweise beträchtlichen Konzentrationserniedrigungen der in der Installationslösung enthaltenen Solute.Auf die Instillation einer blutisotonen NaCl-Lösung reagiert das Jejunum stets mit einer Absorption von Flüssigkeit. Na⁺ und Cl^– werden absorbiert, während HCO₃ ^–, K⁺ und Harnstoff netto sezerniert werden. Im Colon kommt es unter den Bedingungen des 30 min-Versuches zur enterosorption von Flüssigkeit, zur Absorption von osmotisch aktivem Material, Na⁺ und Cl^–, während HCO₃ ^–, K⁺ und Harnstoff sezerniert werden.Auf die Instillation reinen Wassers reagiert das Jejunum mit einer Absorption von Flüssigkeit sowie einer Enterosorption aller geprüften Solute in das Jejunum hinein, daß fast Konzentrationsgleichheit mit dem Plasma eingestellt wird. Im Colon kommt es im 30 min-Versuch teils zur Enterosorption, teils zur Absorption von Flüssigkeit. Nach 60 min wird in allen Fällen eine Absorption von Flüssigkeit beobachtet. Die Gleichgewichtskonzentrationen im Jejunum sind: Osmolarität 296,0 mOsmol/l, Na⁺ 78,6 mMol/l, Cl^– 24,6 mMol/l, HCO₃ ^– 54,8 mMol/l, K⁺ 2,2 mMol/l, Harnstoff 59,9 mg/100 ml. Die analogen Werte für das Colon lauten: Osmolarität 184,0 mOsmol/l, Na⁺ 11,6 mMol/l, Cl^– 12,9 mMol/l, HCO₃ ^– 25,9 mMol/l, K⁺ 16,4 mMol/l, Harnstoff 18,8 mg/100 ml.     

Novel autosomal recessive progressive hyperpigmentation syndrome

We present a family of Iraqui origin with three siblings affected by a novel type of progressive hyperpigmentation syndrome. The generalized initially diffuse, later disseminated hyperpigmentation started in early infancy and increased during childhood. It also affected palms and soles, and the face but spared the cheeks. Additional features were dry, itchy and sunlight sensitive skin, dystrophy of toe nails, hair loss, and myopia, but normal sweat glands. Light and electron microscopy showed signs of pigment incontinence and compound melanosomes as well as fibrillar bodies. The occurrence of this entity in affected siblings from a consanguineous mating suggests autosomal recessive inheritance. Extensive review of the literature showed no previous report with this distinct combination of clinical and microscopic findings.     

Characterization of a novel breast carcinoma xenograft and cell line derived from a BRCA1 germ-line mutation carrier

A human tumor xenograft (L56Br-X1) was established from a breast cancer axillary lymph node metastasis of a 53-year-old woman with a BRCA1 germ-line nonsense mutation (1806C>T; Q563X), and a cell line (L56Br-C1) was subsequently derived from the xenograft. The xenograft carries only the mutant BRCA1 allele and expresses mutant BRCA1 mRNA but no BRCA1 protein as determined by immunoprecipitation or Western blotting. The primary tumor, lymph node metastasis, and xenograft were hypodiploid by DNA flow cytometry, whereas the cell line displayed an aneuploidy apparently developed via polyploidization. Cytogenetic analysis, spectral karyotyping, and comparative genomic hybridization of the cell line revealed a highly complex karyotype with numerous unbalanced translocations. The xenograft and cell line had retained a somatic TP53 missense mutation (S215I) originating from the primary tumors, as well as a lack of immunohistochemically detectable expression of steroid hormone receptors, epidermal growth factor receptor, human epidermal growth factor receptor 2 (HER-2), and keratin 8. Global gene expression analysis by cDNA microarrays supported a correlation between the expression profiles of the primary tumor, lymph node metastasis, xenograft, and cell line. We conclude that L56Br-X1 and L56Br-C1 are useful model systems for studies of the pathogenesis and new therapeutic modalities of BRCA1-induced human breast cancer.     

IFN-gamma-enhanced allergen penetration across respiratory epithelium augments allergic inflammation

BACKGROUND: Respiratory allergen contact is the critical event in the elicitation and boosting of allergen-specific immune responses, as well as in the induction of immediate and late inflammatory reactions. OBJECTIVE: We sought to investigate the influence of various factors of allergic inflammation on the integrity and barrier function of respiratory epithelium for allergens. METHODS: We cultured the human bronchial epithelial cell line 16HBE14o- in a transwell culture system as a surrogate of intact respiratory epithelium and used purified iodine 125-labeled recombinant major birch pollen allergen (rBet v 1) to study the extent, kinetics, and factors influencing transepithelial allergen penetration. RESULTS: Culture supernatants from activated allergen-specific T H 1 clones decreased transepithelial resistance. A screening of various factors (histamine, IFN-gamma, IL-1beta, IL-2, IL-3, IL-4, IL-5, IL-8, IL-12, and TNF-alpha) identified IFN-gamma as a potent factor capable of reducing epithelial barrier properties and enhancing transepithelial allergen penetration. Increased submucosal allergen concentrations caused by IFN-gamma-mediated reduction of epithelial barrier function provoked a more than 7-fold augmentation of histamine release from sensitized basophils. CONCLUSION: These results demonstrate that the T H 1 cell-derived cytokine IFN-gamma facilitates allergen penetration through the respiratory epithelium and thereby can aggravate allergic inflammation.     

Chromosome analysis of 20 breast carcinomas: Cytogenetic multiclonality and karyotypic-pathologic correlations

Short-term cultures from 20 breast carcinomas were analyzed cytogenetically. A normal female chromosome complement was found in 4 cases. Clonal chromosome aberrations were detected in 16 tumors. In 10 tumors, multiple cytogenetic clones were found; in 2 cancers the clones were related, reflecting clonal evolution, but in the remaining 8 tumors the clones were cytogenetically unrelated, indicating clonal heterogeneity in the origin of the tumor parenchyma. Correlation analysis between karyotypic and pathologic parameters indicated that cases with complex karyotypes and/or cytogenetically unrelated clones, when compared with cases with a single simple karyotypic abnormality, were generally of higher histologic malignancy grade, had more mitoses in the histologic sections, and also more often had carcinoma in situ lesions in the same breast. © 1993 Wiley-Liss, Inc.     

Immune Responses to Bile-Tolerant Helicobacter Species in Patients with Chronic Liver Diseases, a Randomized Population Group, and Healthy Blood Donors

Bile-tolerant Helicobacter species such as Helicobacter pullorum, Helicobacter bilis, and Helicobacter hepaticus are associated with hepatic disorders in animals and may be involved in the pathogenesis of chronic liver diseases (CLD) in humans. Antibody responses to cell surface proteins of H. pullorum, H. bilis, and H. hepaticus in serum samples from patients with CLD, a randomized population group, and healthy blood donors were evaluated by using enzyme linked immunosorbent assay (ELISA). The results were compared with the antibody responses to Helicobacter pylori. For analysis of a possible cross-reactivity between bile-tolerant Helicobacter species and H. pylori, sera from a subpopulation of each group were absorbed with a whole-cell extract of H. pylori and retested by ELISA. Results before absorption showed that the mean value of the ELISA units for H. pullorum was significantly higher in patients with CLD than in healthy blood donors (P = 0.01). Antibody reactivity to cell surface protein of H. hepaticus was also significantly higher in the CLD patients than in the healthy blood donors and the population group (P = 0.005 and P = 0.002, respectively). Following the absorption, antibody responses to H. pullorum decreased significantly in all three groups (P = 0.0001 for CLD patients, P = 0.0005 for the population group, and P < 0.0001 for the blood donors), indicating that cross-reactivity between H. pylori and other Helicobacter spp. occurs. The antibody responses to H. hepaticus and H. bilis in CLD patients remained high following absorption experiments compared to ELISA results before absorption. The significance of this finding requires further investigations.     

Impaired neuronal migration and endochondral ossification in Pex7 knockout mice: a model for rhizomelic chondrodysplasia punctata

Rhizomelic chondrodysplasia punctata is a human autosomal recessive disorder characterized by skeletal, eye and brain abnormalities. The disorder is caused by mutations in the PEX7 gene, which encodes the receptor for a class of peroxisomal matrix enzymes. We describe the generation and characterization of a Pex7 mouse knockout (Pex7(-/-)). Pex7(-/-) mice are born severely hypotonic and have a growth impairment. Mortality in Pex7(-/-) mice is highest in the perinatal period although some Pex7(-/-) mice survived beyond 18 months. Biochemically Pex7(-/-) mice display the abnormalities related to a Pex7 deficiency, i.e. a severe depletion of plasmalogens, impaired alpha-oxidation of phytanic acid and impaired beta-oxidation of very-long-chain fatty acids. In the intermediate zone of the developing cerebral cortex Pex7(-/-) mice have an increase in neuronal density. In vivo neuronal birthdating revealed that Pex7(-/-) mice have a delay in neuronal migration. Analysis of bone ossification in newborn Pex7(-/-) mice revealed a defect in ossification of distal bone elements of the limbs as well as parts of the skull and vertebrae. These findings demonstrate that Pex7 knockout mice provide an important model to study the role of peroxisomal functioning in the pathogenesis of the human disorder.     

Transgenic expression of a CD46 (membrane cofactor protein) minigene: Studies of xenotransplantation and measles virus infection

CD46 (membrane cofactor protein) is a human cell-surface regulator of activated complement and a receptor for the measles virus. A CD46 transgenic mouse line with an expression pattern similar to that of human tissues has been produced, to develop an animal model of (i) the control of complement activation by complement regulators in hyperacute rejection of xenografts, and (ii) measles virus infection. The mouse line was made using a CD46 minigene that includes promoter sequence and the first two introns of genomic CD46, which was coinjected into mouse ova with chicken lysozyme matrix attachment region DNA. A high level of CD46 expression in homozygotic transgenic mice was obtained with spleen cells having approximately 75% of the level found on human peripheral blood mononuclear cells. CD46 was detected in all tissues examined by immunohistochemistry, radioimmunoassay and Western blotting, showing that these mice were suitable for transplantation and measles virus infection studies. It also indicated that the transgene included the important regulatory elements of the CD46 promoter. Transgenic spleen cells were significantly protected in vitro from human complement activated by either the classical or alternative pathways and from alternative pathway rat complement. Furthermore, transgenic mouse hearts transplanted to rats regulated complement deposition in an in vivo model of antibody-dependent hyperacute xenograft rejection. Similar to human lymphocytes, transgenic lymphoblasts could be infected in vitro with measles virus; infected cells expressed viral proteins and produced infectious viral particles. The data demonstrate the suitability of this minigene for obtaining high-level CD46 expression sufficient for enhanced resistance of transgenic cells to complement attack and for obtaining wide tissue distribution of CD46, analogous to human tissues and, therefore, useful for comparative studies.     

Informed consent and knee arthroscopies: an evaluation of patient understanding and satisfaction

Fifty patients who had been admitted to a public hospital in Australia for an elective knee arthroscopy were asked to complete a detailed questionnaire prior to theatre, designed to evaluate patient understanding and satisfaction of the informed consent process. While patients generally felt that they received an appropriate amount of information on the nature of their injury and the actual operative procedure, little information was given on possible complications and post-operative care. This study clearly indicates that patients are dissatisfied when they perceive a lack of basic information being given. The findings are of some concern as they suggest that the majority of consents gained in this study were not truly 'informed'. However, recognition by medical staff of the areas that appear to be poorly explained to patients enables these issues to be addressed. This in turn is likely to improve patient understanding of and satisfaction with the consent process.