Bakterien als Ursache allergischer Asthmaanfälle (Versuche mit Keimen aus der Klebsiella-Gruppe)

Zusammenfassung Keime der Klebsiella-Gruppe, Typ 2, in vollsynthetischem eiweißfreiem Nährmedium gezüchtet, eignen sich zur direkten Sensibilisierung von Meerschweinchen sowie zur nachfolgenden Provokation von Asthmaanfällen und anaphylaktischem Schock.Zur Sensibilisierung wurden Keime verwandt, die bei 60° C mit Phenol, Formol oder Ultraschall abgetötet worden waren. Asthmaanfälle konnten durch Inhalation von abgetöteten, aber auch von lebenden Keimen ausgelöst werden. Die Asthmabereitschaft blieb mehrere Monate lang bestehen. Die Anfälle können durch N-Isopropylnoradrenalin zum Verschwinden gebracht werden. Im Grundsätzlichen entsprachen sie Asthmaanfällen, die durch Hühnereiweiß bedingt waren. Unterschiede gegenüber dem Hühnereiweißasthma zeigten sich in geringerer Schockbereitschaft, vermehrter Dyskrinie und dem gelegentlichen Auftreten von Spätreaktionen.Das anaphylaktogene Klebsiella-Antigen ist ein unlöslicher Bestandteil des Bakterienleibes, vermutlich kommt es in der Grenzphase vor.Die Untersuchungen erbringen den tierexperimentellen Beweis, daß Bakterien alsprimäres Allergen Asthma hervorrufen können.FräuleinTrude Schulte danken wir für die wertvolle Mitarbeit. Die Untersuchungen wurden durch ERP-Mittel ermöglicht, für deren Vermittlung wir Herrn Prof. Dr.Hagen, Bundes-Innenministerium, danken.     

The roles of acute and chronic pain in regression of sensory analgesia during continuous epidural bupivacaine infusion

The purpose of this study was to investigate whether regression of sensory analgesia during constant epidural bupivacaine infusion was different in postoperative patients with acute pain than in patients with chronic nonsurgical pain. Sensory levels of analgesia (to pinprick) and pain (on a five-point scale) were assessed hourly for 16 hours during continuous epidural infusion of 0.5% plain bupivacaine (8 ml/hr) in 12 patients with chronic nonsurgical pain and in 30 patients after major abdominal surgery performed under combined bupivacaine and halothane--N2O general anesthesia. No opiates were given. If sensory analgesia decreased more than five segments from the initial level or if the pain score reached 2 (moderate pain), the patient was removed from the study. Initial levels of sensory analgesia after loading doses of 21.8 +/- 0.5 and 19.3 +/- 0.8 ml bupivacaine 0.5% were similar (T3.8 +/- 0.3 and T3.8 +/- 0.5) in the surgical and chronic pain patients, respectively (mean +/- SEM). Of the surgical patients, only 4 of the 30 (13%) maintained the initial level of sensory analgesia, and a pain score below 2 throughout the study compared with 7 of the 12 patients with chronic pain (58%) (P less than 0.01). Mean duration of sensory blockade was significantly longer (P less than 0.005) in the patients with chronic pain than in surgical patients (13.1 +/- 1.2 and 8.5 +/- 0.7 hours, respectively). Thus, surgical injury hastens regression of sensory analgesia during continuous epidural bupivacaine infusion. The underlying mechanism remains to be determined.     

Cancer cell expression of urokinase-type plasminogen activator receptor mRNA in squamous cell carcinomas of the skin

In this study we have used in situ hybridization with radiolabeled antisense RNA probes to examine the expression of mRNA for urokinase-type plasminogen activator and its receptor in histologic samples of squamous cell (n = 7) and basal cell (n = 7) carcinomas of the skin. Messenger RNA for both urokinase-type plasminogen activator and its receptor were expressed in all of the squamous cell carcinomas, but could not be detected in the basal cell carcinomas. In all of the seven squamous cell carcinomas a signal for urokinase-type plasminogen activator receptor mRNA was detected focally in well-differentiated cancer cells surrounding keratinized pearls, and in four specimens urokinase-type plasminogen activator receptor mRNA was in addition expressed by cancer cells at the edge of invasively growing strands of tumor. Urokinase-type plasminogen activator mRNA expression was found in virtually all the cancer cells of the squamous cell carcinomas, and importantly we found, by hybridizations for urokinase-type plasminogen activator and its receptor mRNA on adjacent sections of squamous cell carcinomas, that it was exactly the invading cancer cells that simultaneously expressed both these components required for plasmin-mediated proteolysis at the cell surface. We have previously shown that both urokinase-type plasminogen activator and its receptor mRNA are expressed by the leading-edge keratinocytes in regenerating epidermis during mouse skin wound healing, and that wound healing is impaired in mice made deficient in plasminogen by targeted gene disruption. We propose that there are similarities between the mechanisms of generation and regulation of extracellular proteolysis during skin re-epithelialization and squamous cell carcinoma invasion. The ability of the squamous carcinoma cells to mimic the "invasive" phenotype of re-epithelializing keratinocytes may be one of the factors that make squamous cell carcinomas more aggressive tumors than basal cell carcinomas.     

CD4+ CD8+ (thymocyte-like) T lymphocytes present in blood and skin from patients with atopic dermatitis suggest immune dysregulation

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease expressed early in life. Disease development is primarily determined by as yet unknown genetic factors, leading to the accumulation of activated T lymphocytes in the skin. OBJECTIVES: To investigate the nature of these T cells. METHODS: T-cell lines could be established from AD skin biopsies, but not from normal skin or AD peripheral blood, when placed in RPMI 1640 medium with 10% human AB serum, antibiotics, and the T-lymphocyte growth factors interleukins 2 and 4. The cell lines were subjected to phenotypic analysis using a fluorescence-activated cell sorter and compared with lymphocytes from AD and normal control peripheral blood. RESULTS: T-cell lines from 22 of 24 consecutive skin biopsies taken from 24 adult patients with AD were established. All cells were T lymphocytes expressing several activation markers. A significant proportion of the lymphocytes had stable expression of a CD4+ CD8+ phenotype (26% +/- 6%; mean +/- SEM). Such double-positive T lymphocytes are normally only seen in the thymus and not in the peripheral immune system. CD4+ CD8+ cells in peripheral blood of the patients (12.5% +/- 3.3%) were also detected. CONCLUSIONS: We suggest that a basic pathophysiological change in AD may be a faulty maturation of the T-lymphocyte system, leading to skin inflammation with CD4+ CD8+ T lymphocytes resembling immature T cells. This is likely to lead to skewing of many immune reactions in the patients.     

"Stem cell" origin of the hematopoietic defect in dyskeratosis congenita

We have used the long-term bone marrow culture (LTBMC) system to analyze hematopoiesis in three patients with dyskeratosis congenita (DC), two of whom had aplastic anemia, and the third had a normal blood count (apart from mild macrocytosis) and normal BM cellularity. Hematopoiesis was severely defective in all three patients, as measured by a low incidence of colony-forming cells and a low level of hematopoiesis in LTBMC. The function of the marrow stroma was normal in its ability to support the growth of hematopoietic progenitors from normal marrows seeded onto them in all three cases, but the generation of hematopoietic progenitors from patients marrow cells inoculated onto normal stromas was reduced, thus suggesting the defect to be of stem cell origin. The parents and unaffected brother of one of the families have also been studied in LTBMC and all showed normal hematopoietic and stromal cell function. From this study we speculate that there are some similarities between DC and the defect in the W/Wv mouse.     

Effect of adding albumin to solutions of somatostatin on inhibiting pentagastrin-stimulated acid secretion in dogs

In five conscious dogs with chronic gastric fistulas we studied the effect of somatostatin solutions on pentagastrin-stimulated acid secretion. Somatostatin was dissolved in 0.154 M NaCl alone or in the same amount of saline to which dog albumin had been added to give a 0.5% solution. Somatostatin produced a dose-dependent inhibition of pentagastrin-stimulated gastric secretion. However, the inhibition was significantly less when somatostatin was dissolved in saline as compared to saline plus albumin. This study suggests that albumin should be added to somatostatin solutions to preserve biological activity, and it confirms previous reports indicating that, without albumin, basic peptides have a tendency to stick to infusion systems.     

Dynamic consent: a patient interface for twenty-first century research networks

Biomedical research is being transformed through the application of information technologies that allow ever greater amounts of data to be shared on an unprecedented scale. However, the methods for involving participants have not kept pace with changes in research capability. In an era when information is shared digitally at the global level, mechanisms of informed consent remain static, paper-based and organised around national boundaries and legal frameworks. Dynamic consent (DC) is both a specific project and a wider concept that offers a new approach to consent; one designed to meet the needs of the twenty-first century research landscape. At the heart of DC is a personalised, digital communication interface that connects researchers and participants, placing participants at the heart of decision making. The interface facilitates two-way communication to stimulate a more engaged, informed and scientifically literate participant population where individuals can tailor and manage their own consent preferences. The technical architecture of DC includes components that can securely encrypt sensitive data and allow participant consent preferences to travel with their data and samples when they are shared with third parties. In addition to improving transparency and public trust, this system benefits researchers by streamlining recruitment and enabling more efficient participant recontact. DC has mainly been developed in biobanking contexts, but it also has potential application in other domains for a variety of purposes.