Differences in maintenance of CD8+ and CD4+ bacteria-specific effector-memory T cell populations

Our knowledge about the kinetics and dynamics of complex pathogen-specific CD8(+) T cell responses and the in vivo development of CD8(+) memory T cells has increased substantially over the past years; in comparison, relatively little is known about the CD4(+) T cell compartment. We monitored and directly compared the phenotypical changes of pathogen (Listeria monocytogenes)-specific CD8(+) and CD4(+) T cell responses under conditions leading to effective and long-lasting protective immunity. We found that the general kinetics of bacteria-specific CD8(+) and CD4(+) T cells during the effector and post-effector phases are synchronized. However, later during the memory phase, CD8(+) and CD4(+) T cell populations differ substantially. Whereas CD8(+) memory T cell populations with immediate effector function are readily detectable in lymphoid and non-lymphoid tissues and remain remarkably stable in size, antigen-specific CD4(+) effector-memory T cells decline continuously in frequency over time. These findings have important implications for the better understanding of the in vivo development of protective immunity towards intracellular pathogens.     

Über zwei neue Fälle von hereditärer nichtsphärocytärer hämolytischer Anämie bei Glucose-6-Phosphat-Dehydrogenase-Defekt in einer norddeutschen Familie

Zusammenfassung Bei zwei Geschwistern norddeutscher Abstammung findet sich das Krankheitsbild einer hereditären nichtsphärocytären hämolytischen Anämie, dem ein Defekt der Glucose-6-Phosphatdehydrogenase der Erythrocyten zugrundeliegt. Das Protein weist von der Norm abweichende qualitative Eigenschaften auf. Die histochemisch belegbare Heterozygotie der Mutter für die anomale genetische Information wird bei biochemischer Untersuchung der Gesamtpopulation der Erythrocyten durch den relativ hohen Anteil der normalen Erythrocyten überdeckt. Das klinische Bild des einen der beiden Geschwister ist durch ein zusätzliches kongenitales Vitium cordis (Vorhofseptumdefekt vom Ostium secundum-Typ) kompliziert.

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Summary Two brothers of a family in North-Germany have a hereditary non spherocytic hemolytic anemia with glucose-6-phosphate dehydrogenase deficiency in erythrocytes. The activity of the enzyme was 20% resp. 10% of that found in normal red cells. In the patients the enzyme protein were showing not only a quantitative difference from normal activity, but also a qualitative abnormality of the protein. In the parents the behaviour of the enzyme protein is normal. The total enzyme level of the mother's red cells is in the normal range, but histochemically the heterozygosity (ie146-1) were found. One of the patients were splenectomized without response. In the other patient a congenital heart disease (ostium secundum defect) is associated with the anemia.

     

Acute changes of coagulation and fibrinolysis parameters after experimental thromboembolic stroke and thrombolytic therapy

Thrombolysis is the only effective pharmaceutical therapy in acute ischemic stroke in humans but has a high risk of intracerebral hemorrhage. We aimed to establish an animal model to study changes of coagulation and fibrinolytic parameters during thromboembolic ischemic stroke and thrombolysis with recombinant tissue plasminogen activator (rt-PA). We used a thromboembolic stroke model in the rat. Animals were treated with rt-PA thrombolysis (n = 10) and compared with untreated (n = 10), sham operated (n = 10) and control animals (n = 20). Coagulation parameters (APTT, PT, TT, fibrinogen, AT III, TAT) and fibrinolytic parameters (t-PA antigen concentration, t-PA activity, PAI-1 concentration, PAI activity, plasminogen, antiplasmin) were measured at two time points (2.5 and 5 h after stroke induction) with a battery of commercially available test kits. We observed an (1) initiation of coagulation and inhibition of fibrinolysis by the operation procedure itself, (2) simultaneous activation of fibrinolysis and its inhibitors after stroke induction and (3) potent initiation of fibrinolysis and consumption of fibrinolysis inhibitors after rt-PA therapy of stroke. We established a model system to monitor coagulation and fibrinolysis during thrombolytic therapy of stroke in the rat. This model may be used to study the influence of these parameters on hemorrhagic stroke transformation and outcome in experimental stroke in future.     

Pyogenic granuloma: an unrecognized cause of gastrointestinal bleeding

Pyogenic granuloma is a lobular capillary hemangioma that mostly occurs on the skin, but it is also encountered on the mucosal surface of the oral cavity. Only a few cases in other parts of the digestive tract have been reported in Japanese patients. In this report, two Caucasian patients are described, who presented with gastrointestinal bleeding due to the presence of a pyogenic granuloma. One was located in the distal esophagus and could be treated with local excision and laser-photocoagulation therapy. The other one was located in the small intestine and was removed by surgical resection. Although extremely rare, pyogenic granuloma as a cause of gastrointestinal bleeding needs consideration. The lesion is benign, presumably reactive and can be adequately treated by excision or laser photocoagulation. Immunohistochemistry and/or polymerase chain reaction for herpesvirus 8 can reliably distinguish pyogenic granuloma from Kaposis sarcoma, an important differential diagnosis.     

Rapid Report

Coexpression of KCNQ2 and KCNQ3 channels results in a 10-fold increased current amplitude compared to that of KCNQ2 alone, suggesting the formation of heteromultimeric channels. There is no interaction of either channel with KCNQ1. We evaluated the C-terminus as a potential interaction domain by construction of chimeras with interchanged C-termini of KCNQ1, KCNQ2 and KCNQ3 and functional expression in Xenopus oocytes. The chimera of KCNQ1 with a KCNQ2 C-terminus (Q1ctQ2) showed an 8-fold increase in current amplitude, and Q1ctQ3 a 3-fold increase when coexpressed with KCNQ3 and KCNQ2, respectively, indicating that the C-terminus contains an interaction domain. To characterize this interacting region, we studied further chimeras of KCNQ1 containing different parts of the KCNQ3 C-terminus for interaction with KCNQ2. We also evaluated short sequences of the KCNQ2 C-terminus for a dominant-negative effect on Q1ctQ3. According to the results of these experiments, functional interaction of KCNQ2 and KCNQ3 requires a highly conserved region of about 80 amino acids, previously called the A-domain, plus either 40 residues downstream of the A-domain (B-domain) or the proximal C-terminus between S6 and the A-domain. Furthermore, the chimeras Q1ctQ3 and Q2ctQ3 showed > 10-fold increased current amplitudes compared to KCNQ1 or KCNQ2 alone and a strong depolarizing shift of voltage-dependent activation. The proximal part of the KCNQ3 C-terminus was necessary to produce these effects. Our results indicate that specific parts of the C-terminus enable the interaction between KCNQ2 and KCNQ3 channels and that different parts of the KCNQ3 C-terminus are important for regulating current amplitude.     

Elektronenmikroskopische Untersuchungen an der Tumor-Bindegewebsgrenze beim Mammacarcinom der Frau

Zusammenfassung 1. Die Epithel-Bindegewebsgrenze wurde bei 36 Mammacarcinomen, einem Fibroadenom der Mamma und einer proliferierenden Mastopathie systematisch elektronenmikroskopisch untersucht.2. Während das Epithel bei Fibroadenom und Mastopathie überall durch eine geschlossene, elektronenmikroskopisch eindeutig darstellbare Basalmembran vom umgebenden Bindegewebe abgegrenzt wird, fehlt eine Basalmembran in der Regel beim Mammacarcinom.3. Die Carcinomzellen liegen dem umgebenden Bindegewebe entweder mit glatter oder unregelmäßiger Zellmembran an. Die Zerklüftung der Zelloberfläche stellt sich als submikroskopisches Äquivalent von zwei verschiedenen biologischen Vorgängen an der Tumor-Stroma-Grenze dar: 1. einer Phagocytose von Fibrin und Erythrocyten und 2. einer Antigen-Antikörperreaktion.4. Das peritumorale Bindegewebe zeigt ausnahmslos eine hochgradige Aktivitätssteigerung der Fibroblasten mit vermehrter Kollagensynthese. Außerdem treten aktivierte Muskelzellen auf. Elastische Elemente gehen zugrunde.5. Bei einem Ductuscarcinom einer 38jährigen Frau war eine peritumorale Mastocytose nachweisbar; der wachstumshemmende Effekt des Heparins wird diskutiert.6. Der (in 2 Fällen beobachtete) exzessive Lymphocytenreichtum des parablastomatösen Stromas spricht für eine lokale immunologische Tumorabwehrreaktion.7. Dem nach Entdifferenzierung der Zelle und Basalmembranverlust des Parenchyms wirksam werdenden Wachstumsdruck des Tumorgewebes mit Phagocytoseleistung als Ausdruck der Aggressivität des Malignoms begegnet das Stroma mit Stoffwechselaktivierung, Phagocytose, Faserneubildung, Antihyaluronidase-Effekt und Antikörperbildung. Die Prognose eines Tumors ist das Ergebnis komplexer, temporär differenter biologischer Faktoren.

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Electron microscopic studies of the junction of tumor and connective tissue in breast carcinoma of women

Summary An electron microscopic study was made of the Tumor-connectine tissue junction of 36 breast carcinomas, of 1 fibroadenoma, and of 1 proliferating mastopathy.The basement membranes were seen in the fibroadenoma and the proliferating mastopathy but normally were lacking in the mammary gland carcinomas.The malignant epithel cells adjoined the contiguous connective tissue by either smooth or irregular cell membranes. The irregularity of the cell membranes is interpreted as the submicroscopic equivalent of two different biological processes at the junction of tumor and connective tissue: 1) the phagocytosis of fibrin and red blood cells; 2) the reaction between antigen and antibody. The connective tissue surrounding the tumor showed increased activity of fibroblasts. Collagen fibres appeard newly formed. Muscle cells with increased metabolism were found. In two cases the peritumorous tissue showed an excessive abundance of lymphocytes suggesting a local immunological reaction of the organism against neoplastic tissue.In one case mast cells were found increased in the connective tissue. A reaction of heparin against hyaluronidasis is discussed.The prognosis of a malignant tumor is the sum of many complex, temporarily different biological factors.

     

Heat shock protein 60 from Chlamydia pneumoniae elicits an unusual set of inflammatory responses via Toll-like receptor 2 and 4 in vivo

Heat shock protein 60 (HSP60) from Chlamydia pneumoniae was described to trigger in vitro inflammatory and cytokine responses including TNF and IL-12p40. Although it can be found in atherosclerotic plaques of patients, the stimulatory potential of chlamydial and other HSP60 in vivo is unclear. We now report that chlamydial HSP60 fails to induce TNF expression in vivo, and significant serum levels of IL-12p40 are only found upon intraperitoneal injection of high doses of HSP60 or after intravenous application. Upon purification of chlamydial HSP60 with polymyxin B-agarose columns, its ability to induce TNF secretion in vitro is much reduced. However, purified chlamydial HSP60 causes increased serum levels of the CXC chemokines KC and MIP2 in vivo, as well as a strong accumulation of polymorphonuclear neutrophils (PMN) in the peritoneal cavity upon intraperitoneal challenge. With respect to PMN accumulation, chlamydial HSP60 is more potent than endotoxin or the CpG oligonucleotide 1668. The responses observed are completely abolished in Toll-like receptor (TLR)2/4-double-deficient mice, while single-deficient mice respond almost normally. Furthermore, KC induction and PMN accumulation are largely dependent on MyD88. In conclusion, HSP60 from C. pneumoniae triggers inflammatory responses in vivo that differ from responses induced by endotoxin or CpG oligonucleotides and are dependent on TLR2 and 4.     

Initial evaluation of a continuous speech recognition program for radiology

The aims of this work were to measure the accuracy of one continuous speech recognition product and dependence on the speaker's gender and status as a native or nonnative English speaker, and evaluate the product's potential for routine use in transcribing radiology reports. IBM MedSpeak/Radiology software, version 1.1 was evaluated by 6 speakers. Two were nonnative English speakers, and 3 were men. Each speaker dictated a set of 12 reports. The reports included neurologic and body imaging examinations performed with 6 different modalities. The dictated and original report texts were compared, and error rates for overall, significant, and subtle significant errors were computed. Error rate dependence on modality, native English speaker status, and gender were evaluated by performing ttests. The overall error rate was 10.3 +/- 3.3%. No difference in accuracy between men and women was found; however, significant differences were seen for overall and significant errors when comparing native and nonnative English speakers (P = .009 and P = .008, respectively). The speech recognition software is approximately 90% accurate, and while practical implementation issues (rather than accuracy) currently limit routine use of this product throughout a radiology practice, application in niche areas such as the emergency room currently is being pursued. This methodology provides a convenient way to compare the initial accuracy of different speech recognition products, and changes in accuracy over time, in a detailed and sensitive manner.