Endosonography (ES) in the diagnosis of recurrent cancer of the rectum.

The ability of endosonography (ES) to detect local recurrence after "curative" surgery for rectal cancer was investigated in 65 patients. Fifteen patients developed local recurrence. All of these 15 patients had ES evidence of recurrence; in four cases recurrence was detected by ES alone. Ten of the 15 patients with local failure underwent reoperation. Four patients were candidates for reoperation for cure. Three patients with radical reoperation belonged to the group in which recurrence was detected by ES alone. ES is able to detect small tumors before there is evidence of recurrence in other available forms of examination.     

Immunohistochemical Localization of Neuropeptide Y in Nerves of the Male Genital Tract of the Photoperiodically Responsive Djungarian Hamster, Phodopus Sungoras/Immunhistochemische Lokalisation von Neuropeptid Y in Nerven der männlichen Genitalorgane des photoperiodisch sensiblen Djungarischen Zwerghamsters, Phodopus sungorus

Neuropeptide Y (NPY) was demonstrated by immunohistochemistry in nerves of the male genital tract of Phodopus sungorus at long (LD 16:8) und short (LD 8:16) photoperiods. No immunoreactive nerve fibres could be demonstrated in the testis, caput and corpus epididymidis and the ventral prostate gland. Dense networks of NPY-containing nerve fibers were demonstrated in the smooth muscle layer of the sperm-transporting duct, beginning in the cauda epididymidis with increasing density towards the distal part of the ductus deferens, and in the smooth muscle layer of the seminal vesicles. At short photoperiods, the density of the NPY-containing nerve plexus decreased only in the smooth muscle layer of the ductus deferens. A "trophic" influence of the large smooth muscle cells of the ductus deferens on their nerves not only in regard to their noradrenaline, but also on their NPY content is discussed.     

Ureteral stents — materials and new forms

Summary Three different types of polymers are currently used for self-retained ureteral stents: thermoplastic materials such as polyurethanes, and thermoset elastomers such as silicone and hydrogels. Polyurethane stents are easy to form and have high drainage capacity, whereas silicone shows the best biocompatibility but a lower drainage efficacy than the former. A mock urinary system consisting of a collecting system and a 9-F tube was used to evaluate the flow characteristics of various double-pigtail stents in cases of urinary obstruction. For simulation of an unobstructed urinary system a human urogenital system was used. Inner flow polyurethane stents showed the best drainage as compared with inner flow silicone and outer flow ESWL stents in an obstructed ureter, whereas ESWL stents maintained the best flow in an unobstructed ureter or in respect to conventional stents with obstructed sideports.     

Functional analysis of the cag pathogenicity island in Helicobacter pylori isolates from patients with gastritis, peptic ulcer, and gastric cancer

Helicobacter pylori is the causative agent of a variety of gastric diseases, but the clinical relevance of bacterial virulence factors is still controversial. Virulent strains carrying the cag pathogenicity island (cagPAI) are thought to be key players in disease development. Here, we have compared cagPAI-dependent in vitro responses in H. pylori isolates obtained from 75 patients with gastritis, peptic ulcer, and gastric cancer (n = 25 in each group). AGS gastric epithelial cells were infected with each strain and assayed for (i) CagA expression, (ii) translocation and tyrosine phosphorylation of CagA, (iii) c-Src inactivation, (iv) cortactin dephosphorylation, (v) induction of actin cytoskeletal rearrangements associated with cell elongation, (vi) induction of cellular motility, and (vii) secretion of interleukin-8. Interestingly, we found high but similar prevalences of all of these cagPAI-dependent host cell responses (ranging from 56 to 80%) among the various groups of patients. This study revealed CagA proteins with unique features, CagA subspecies of various sizes, and new functional properties for the phenotypic outcomes. We further showed that induction of AGS cell motility and elongation are two independent processes. Our data corroborate epidemiological studies, which indicate a significant association of cagPAI presence and functionality with histopathological findings in gastritis, peptic ulcer, and gastric cancer patients, thus emphasizing the importance of the cagPAI for the pathogenicity of H. pylori. Nevertheless, we found no significant association of the specific H. pylori-induced responses with any particular patient group. This may indicate that the determination of disease development is highly complex and involves multiple bacterial and/or host factors.     

Activation of influenza A viruses by trypsin treatment.

A comparative analysis has been carried out on the infectivity of virus of several influenza A strains grown in different host systems. Strains A/swine/Shope/31 (Hsw1N1), A/PR/8/34 (HON1), A/FM/1 (H1N1), A/Singapore/1/57 (H2N2), A/equine/Miami/1/63 (Heq2Neq2), and A/chick/Germany/49 (Hav2Neq1) exhibit host-dependent differences in infectivity. Virions grown in embryonated eggs and cultures of chorioallantoic membrane cells are highly infectious, whereas virions grown in cultures of chick embryo cells have a low infectivity that significantly increases after treatment in vitro with trypsin. In contrast, fowl plague viruses do not show host-dependent variations in infectivity. Virions grown in all host systems tested are highly infectious, and the infectivity of virions grown in chick embryo cells cannot be enhanced by trypsin treatment.The activation of virus particles appears to be based on the cleavage of hemagglutinin glycoprotein HA. This concept is supported by the following observations: (i) In virions of low infectivity only uncleaved glycoprotein HA can be detected. Virions of high infectivity exhibit complete or at least partial cleavage of the hemagglutinin. (ii) The activation of virions by trypsin treatment is always paralleled by cleavage of HA. (iii) Cleavage of HA is the only effect which can be detected after trypsin treatment. The neuraminidase is neither inactivated nor removed from the virion. (iv) Studies on recombinants of virus N and fowl plague virus (Rostock) show that host-dependent variation of infectivity and activation by trypsin, features specific for parent virus N, are found only with recombinant N(H)-FPV/Ro(N) but not with recombinant FPV/Ro(H)-N(N).Efficient plaque formation and serial passages are possible only if highly infectious particles are formed in a given host system. Thus, all strains analyzed undergo, in the absence of trypsin, successive growth cycles in eggs and chorioallantoic membrane cells and form plaques in chorioallantoic membrane cells. In contrast, in chick embryo cells only viruses containing the fowl plague virus hemagglutinin produce plaques and replicate under multiple cycle conditions without the addition of trypsin.The data show that cleavage of HA is not a precondition for virus assembly and hemagglutinating activity, but that it is necessary for infectivity. These findings are compatible with the hypothesis that, in addition to its role in adsorption, the hemagglutinin has another function in the infection process and cleavage is required for this function.     

Über die sogenannten Myxome des Herzens

Zusammenfassung Die 15jährige Patientin litt wiederholt an Angina, die wohl über einer latenten Sepsis zu einer Endokardveränderung führte. Diese bedingte einen Thrombus des linken Vorhofes in der Gegend der Fossa ovalis. Aus der Zeit rühren embolische Narben der Milz und der linken Niere her. Unter eintretender Organisation des Thrombus wurde er durch den Blutstrom zu einem polypenförmigen Gebilde abgeglättet und ausgezogen. Er reichte nun durch das Ostium venosum sin. hindurch in die linke Herzkammer hinein und täuschte klinisch eine Insuffizienz der Klappe mit Stenose des Ostiums vor. Der organisierte Thrombus entartete in seinem größten Teile schleimig, während der neu angebildete Teil an der Basis auch jetzt noch wie ein typischer organisierter Thrombus aussah. Mikroskopisch konnte ich alle Bestandteile nachweisen, die die Autoren in den Myxomen beschrieben. Auch fand ich entzündliche Elemente, ebenso hyalines Fibrin, besonders in dem jüngeren, basalen Teile des Gebildes. Aus alledem komme ich zur Diagnose Thrombus myxomatodes und meine, daß auch alle die bisher beschriebenen primären Tumoren des endokards, außer den bösartigen Gewächsen, organisierte Thromben darstellen.Mit 5 Textabbildungen.     

Effect of tissue fixatives on telomere length determination by quantitative PCR

Telomere length is a well established marker of cellular senescence and thus biological age. Quantitative PCR allows the determination even from very low amounts of tissue by using telomere specific and single copy gene primers. Comparing a directly processed tissue sample to a 4% formaldehyde fixed one showed a significantly reduced efficiency of PCR reactions (mainly in single copy gene experiments) in a storage time-dependent manner resulting in an artificial increase in reported relative telomere length. This effect was not seen when the tissue was stored in RNA later solution. In summary, telomere length determination from formaldehyde fixed material by quantitative PCR is not a reliable method. Unfortunately therefore, many easily accessible tissue samples from pathology laboratories are unsuitable for this technique.     

September 2002: 24-year-old female with a 6-month history of seizures

The September 2002 COM. A 24-year-old female presented with a history of 3 generalized seizures, the first of which had occurred 6 months before admission. Her neurological examination was normal, but upon admission her MRI showed a small cystic lesion in the left parieto-occipital region. The lesion was hyper-intense on T-2 weighted images and did not show contrast enhancment. At surgery, the tumor was found to be deep to the cortex and was a cyst with amber fluid surrounded by gliotic brain. Microscopically, the tumor was well-demarcated from the surrounding tissues, which showed reactive changes, including Rosenthal fibers. The tumor was composed of GFAP-positive glial cells, which were arranged in a pseudopapillary fashion around blood vessels. In between, the tumor cells were positive for neuronal markers. The diagnosis was papillary glioneuronal tumor (PGNT), a relatively recently described lesion that may be a variant of ganglioglioma. The current literature on PGNTs is reviewed.     

Asynchronous replication timing of imprinted loci is independent of DNA methylation,but consistent with differential subnuclear localization

Genomic imprinting in mammals marks the two parental alleles resulting in differential gene expression. Imprinted loci are characterized by distinct epigenetic modifications such as differential DNA methylation and asynchronous replication timing. To determine the role of DNA methylation in replication timing of imprinted loci, we analyzed replication timing in Dnmt1- and Dnmt3L-deficient embryonic stem (ES) cells, which lack differential DNA methylation and imprinted gene expression. Asynchronous replication is maintained in these ES cells, indicating that asynchronous replication is parent-specific without the requirement for differential DNA methylation. Imprinting centers are required for regional control of imprinted gene expression. Analysis of replication fork movement and three-dimensional RNA and DNA fluorescent in situ hybridization (FISH) analysis of the Igf2-H19 locus in various cell types indicate that the Igf2-H19 imprinting center differentially regulates replication timing of nearby replicons and subnuclear localization. Based on these observations, we suggest a model in which cis elements containing nonmethylation imprints are responsible for the movement of parental imprinted loci to distinct nuclear compartments with different replication characteristics resulting in asynchronous replication timing.     

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.