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Showing papers by "University of Erlangen-Nuremberg published in 1995"


Journal ArticleDOI
TL;DR: In this article, a model of the deposition-splashing boundary in terms of Reynolds number and Ohnesorge number is presented, which is only achieved if the normal velocity component of the impinging droplets is used in these dimensionless numbers.

1,073 citations


Journal ArticleDOI
TL;DR: It is concluded, that studies which do not control premorbid intelligence have to be considered as a “malpractice” and should not be accepted by scientists.
Abstract: The discrepancy between current and premorbid ability is a relevant indicator of acquired mental impairment, which itself is closely related to general cerebral dysfunction. The use of tests sensitive to cerebral dysfunction, raises relatively few problems compared with tests being resistant that are used to estimate premorbid mental ability. For premorbid ability, verbal tests assessing knowledge, especially vocabulary, have been shown to be valid. A test, possibly more insensitive to brain dysfunction than the ones usually administered, is the multiple choice vocabulary test (MWT = Mehrfachwahl-Wortschatz-Test). At present only German versions are available. They are presented in some detail because of their advantages. Construction of the MWT is simple, and it can be easily administered in about five minutes. The results correlate fairly well with global IQ in healthy adults (median of r = 0.72 in 22 samples) and are more insensitive to current disturbances than such tests as the WAIS vocabulary test. The limitations of premorbid tests with respect to diagnostic validity are discussed. It is concluded, that studies which do not control premorbid intelligence have to be considered as a "malpractice" and should not be accepted by scientists.

574 citations


Journal ArticleDOI
TL;DR: Electrostimulation to the sacral spinal nerves is applied to increase function of the striated muscles of the anal sphincter to promote continence with intermittent stimulation and preliminary data indicate that anal closure pressure increases with the duration of stimulation.

520 citations



Journal ArticleDOI
TL;DR: In this paper, the filler particles react with carbon from the polymer precursor or nitrogen from the reaction gas atmosphere to form new (oxy) carbide or (oxy)-nitride phases embedded in a nanocrystalline Si-O-C(-N) matrix.
Abstract: Manufacturing of bulk ceramic components from materials in the system Si-Me-C-N-O (Me = Ti, Cr, V, Mo, Si, B, CrSi2, MoSi2, etc.) from preceramic organosilicon polymers - such as poly(carbosilanes), poly(silazanes), or poly(siloxanes) - has become possible by incorporating reactive filler particles into the liquid or solid polymer pre-cursor. During pyrolytic decomposition of the polymer matrix, the filler particles react with carbon from the polymer precursor or nitrogen from the reaction gas atmosphere to form new (oxy)carbide or (oxy)nitride phases embedded in a nanocrystalline Si-O-C(-N) matrix. The selective expansion encountered in the filler phase reaction can be used to compensate for the polymer shrinkage upon pyrolytic conversion. The formation of a transient pore net-work between 400° and 1000°C is governed by the polymer decomposition as well as the filler particle reaction kinetics. Thus, the properties of the oxycarbonitride composite materials can be tailored by controlling the microstructures of the polymer-derived matrix phase, the filler network, and the residual porosity. Near-net-shape forming of bulk ceramic components, even with complex geometry, is possible, making novel applications of polymer-derived bulk materials in biomedical, electrical, and mechanical fields highly interesting.

408 citations


Journal ArticleDOI
TL;DR: A direct link between MSH2 deficiency and the pathogenesis of cancer is established and these mutant mice should be good models to study the progression of tumours and also to screen carcinogenic and anti–cancer agents.
Abstract: Alterations of the human MSH2 gene, a homologue of the bacterial MutS mismatch repair gene, co-segregate with the majority of hereditary non-polyposis colon cancer (HNPCC) cases. We have generated homozygous MSH2-/- mice. Surprisingly, these mice were found to be viable, produced offspring in a mendelian ratio and bred through at least two generations. Starting at two months of age homozygous-/- mice began, with high frequency, to develop lymphoid tumours that contained microsatellite instabilities. These data establish a direct link between MSH2 deficiency and the pathogenesis of cancer. These mutant mice should be good models to study the progression of tumours and also to screen carcinogenic and anti-cancer agents.

382 citations


Journal ArticleDOI
TL;DR: This paper conducted a short-term longitudinal study examining the structure of coping behavior and the relationship between coping style and depression during adolescence, finding that adolescents who are able to elicit social support, engage in problem solving, and cognitively restructure events within a positive light are more likely to successfully negotiate the challenges of adolescence.
Abstract: We conducted a short-term longitudinal study examining the structure of coping behavior and the relationship between coping style and depression during adolescence. The sample consisted of 603 adolescents in Grades 6–11 who were surveyed in the fall of 1989 and again in the fall of 1990. A two-dimensional model of coping was found using confirmatory factor analysis with the factors being approach and avoidant coping. Four cross-sectional and seven longitudinal coping groups were formed to explore group differences in depression. Approach copers reported the fewest symptoms of depression, while avoidant copers reported the most. Subjects who changed over time from approach to avoidant coping evidenced a significant increase in depressive symptoms, whereas subjects who switched from avoidant to approach coping displayed a significant decrease in depression over a one-year period. These findings imply that adolescents who are able to elicit social support, engage in problem solving, and cognitively restructure events within a positive light are more likely to successfully negotiate the challenges of adolescence.

376 citations


Journal ArticleDOI
TL;DR: Glycolytic intermediates, stimulating the corresponding protein kinase and the P‐ser‐HPr/CcpA complex formation, provide a link between glycolysis activity and carbon catabolite repression.
Abstract: CcpA, the repressor/activator mediating carbon catabolite repression and glucose activation in many Gram-positive bacteria, has been purified from Bacillus megaterium after fusing it to a His tag. CcpA-his immobilized on a Ni-NTA resin specifically interacted with HPr phosphorylated at seryl residue 46. HPr, a phospho-carrier protein of the phosphoenolpyruvate: glycose phosphotransferase system (PTS), can be phosphorylated at two different sites: (i) at His-15 in a PEP-dependent reaction catalysed by enzyme I of the PTS; and (ii) at Ser-46 in an ATP-dependent reaction catalysed by a metabolite-activated protein kinase. Neither unphosphorylated HPr nor HPr phosphorylated at His-15 nor the doubly phosphorylated HPr bound to CcpA. The interaction with seryl-phosphorylated HPr required the presence of fructose 1,6-bisphosphate. These findings suggest that carbon catabolite repression in Gram-positive bacteria is a protein kinase-triggered mechanism. Glycolytic intermediates, stimulating the corresponding protein kinase and the P-ser-HPr/CcpA complex formation, provide a link between glycolytic activity and carbon catabolite repression. The sensitivity of this complex formation to phosphorylation of HPr at His-15 also suggests a link between carbon catabolite repression and PTS transport activity.

367 citations


Journal ArticleDOI
TL;DR: There were significant correlations between seizure reduction and increases in asparagine, phenylalanine, PEA, alanine and tryptophan concentrations and Chronic VNS appears to have an effect on various amino acids pools in the brain.

320 citations


Journal ArticleDOI
TL;DR: Three components involved in catabolite repression of gene expression in Bacillus have been identified and direct protein‐protein interaction between CcpA and HPr(Ser‐P) was recently demonstrated and constitutes a link between metabolic activity and CR.
Abstract: Three components involved in catabolite repression (CR) of gene expression in Bacillus have been identified. The cis-acting catabolite responsive element (CRE), which is present in many genes encoding carbon catabolic enzymes in various species of the Gram-positive bacteria, mediates CR of several genes in Bacillus subtilis, Bacillus megaterium, and Staphylococcus xylosus. CR of most genes regulated via CRE is also affected by the trans-acting factors CcpA and HPr. Similarities between CcpA and Lac and Gal repressors suggest binding of CcpA to CRE. HPr, a component of the phosphoenolpyruvate:sugar phosphotransferase system, undergoes regulatory phosphorylation at a serine residue by a fructose-1,6-diphosphate-activated kinase. A mutant of HPr, which is not phosphorylatable at this position because of an exchange of serine to alanine, lacks CR of several catabolic activities. This mutant phenotype is similar to the one exhibited by a ccpA mutant. Direct protein-protein interaction between CcpA and HPr(Ser-P) was recently demonstrated and constitutes a link between metabolic activity and CR.

298 citations


Journal ArticleDOI
TL;DR: A major role of local acidosis in long lasting excitation and sensitization of cutaneous nociceptors has recently been demonstrated and this condition is mimicked in a rat skin-saphenous nerve preparation in vitro which allows direct application of chemicals to the isolated receptive fields at the corium side.
Abstract: A major role of local acidosis in long lasting excitation and sensitization of cutaneous nociceptors has recently been demonstrated. In inflamed tissue, acid pH meets with a mixture of inflammatory mediators which, by themselves, stimulate nociceptors though being subject to profound tachyphylaxis. We have mimicked this condition in a rat skin-saphenous nerve preparation in vitro which allows direct application of chemicals to the isolated receptive fields at the corium side. Stimulant solutions used were CO2-saturated "synthetic interstitial fluid" (CO2-SIF, pH 6.1), and "inflammatory soup" (IS) in submaximal concentration containing bradykinin, 5-HT, histamine, prostaglandin E2 (all 10(-6) M in SIF at 38.5 degrees C and pH 7.0), and a combination made of CO2-saturated IS (CO2-IS, pH 6.1). Identified mechano-heat sensitive ("polymodal") C-fiber terminals (n = 36) were treated with these solutions for 5 min at 10 min intervals or for 30 min of sustained stimulation: 20 units responded to CO2-SIF, 12 to IS, whereas 27 units (75%) were excited by CO2-IS. Thus, 6 out of 15 units insensitive to either of the two basic solutions were stimulated by their combination. This enhanced effect of CO2-IS was also expressed in shorter latencies (than with CO2-SIF) and in a significantly larger mean response magnitude of the fiber population: 152 spikes with the combination versus 45 spikes evoked by IS and 93 spikes by CO2-SIF (n = 25; p < 0.002 and < 0.02, respectively, Wilcoxon test).(ABSTRACT TRUNCATED AT 250 WORDS)

Journal ArticleDOI
TL;DR: The Bacillus subtilis dlt operon (D-alanyl-lipoteichoic acid) is responsible for D-alanine esterification of both lipoteichic acid (LTA) and WTA.


Journal ArticleDOI
TL;DR: In this paper, the mean velocity and statistical moments of turbulent velocity fluctuations in the near-wall region of a fully developed pipe flow at low Reynolds numbers were measured using laser-Doppler measurements.
Abstract: This paper presents laser-Doppler measurements of the mean velocity and statistical moments of turbulent velocity fluctuations in the near-wall region of a fully developed pipe flow at low Reynolds numbers. A refractive-index-matched fluid was used in a Duran-glass test section to permit access to the near-wall region without distortion of the laser beams. All measurements were corrected for the influence of the finite size of measuring control volume. Measurements of long-time statistical averages of all three fluctuating velocity components in the near-wall region are presented. It is shown that the turbulence intensities in the wall region do not scale with inner variables. However, the limiting behaviour of the intensity components very close to the wall show only small variations with the Reynolds number. Measurements of higher-order statistical moments, the skewness and flatness factors, of axial and tangential velocity components confirm the limiting behaviour of these quantities obtained from direct numerical simulations of turbulent channel flow. The comparison of measured data with those obtained from direct numerical simulations reveals that noticeable discrepancies exist between them only with regard to the flatness factor of the radial velocity component near the wall. The measured v’ flatness factor does not show the steep rise close to the wall indicated by numerical simulations. Analysis of the measured data in the near-wall region reveals significant discrepancies between the present LDA measurements and experimental results obtained using the hot-wire anemometry.

Journal ArticleDOI
TL;DR: In this article, the authors compared electron-beam computed tomography (CT) and coronary angiography for depiction of coronary artery stenoses and found significant enhancement within the vessel lumen (P <.001) permitted selective reconstruction of the inner coronary artery lumen.
Abstract: PURPOSE: To compare electron-beam computed tomography (CT) and coronary angiography for depiction of coronary artery stenoses. MATERIALS AND METHODS: In 27 patients (age range, 50-70 years), electrocardiographically triggered axial electron-beam CT scans of the heart were obtained during breath hold and intravenous administration of contrast agent. Coronary arteries were reconstructed three-dimensionally. Electron-beam CT and angiographic results were compared. RESULTS: Significant enhancement within the vessel lumen (P < .001) permitted selective reconstruction of the inner coronary artery lumen. Nine of 11 high-grade stenoses and all five occlusions in the proximal left anterior descending artery and three of five high-grade right coronary artery stenoses were clearly identified. Recognition of stenosis of the left circumflex artery was not reliable. Success after percutaneous transfemoral coronary angioplasty was documented in five of five patients by visualizing the increase in vessel diameter at repe...

Journal ArticleDOI
TL;DR: The results suggest that MECA‐32 antigen expression is temporally and spatially correlated with the development of the blood brain barrier.
Abstract: Few markers specific for mouse endothelium exist. We describe here one such marker, MECA-32, a monoclonal antibody which shows high specificity for mouse endothelium in both embryonic and mature tissues. The MECA-32 antigen has a M(r) of 50-55 x 10(3) under reducing conditions and M(r) of 100-120 x 10(3) under nonreducing conditions. It is expressed on most endothelial cells in the embryonic and in the adult mouse, with the exception of the brain, skeletal, and cardiac muscle, where it has a more restricted distribution. In skeletal and cardiac muscle only small arterioles and venules express the MECA-32 antigen, while in the brain its expression is negatively correlated with the differentiation of the vasculature to form the blood brain barrier. Interestingly, during embryonic development the antigen occurs on the brain vasculature up to day 16 of gestation (E16), whereupon it disappears. The embryonic brain is an avascular organ anlage which is vascularized by ingrowth of external blood vessels. Differentiation of the vasculature to form the blood brain barrier occurs at approximately E16 in the mouse. This differentiation correlates with the downregulation of MECA-32 antigen expression. Between E12 and E16 MECA-32 detects most endothelial cell surfaces of the blood vessels in the brain. No MECA-32 antigen is found in the brain at E17 or any later stage of development with the exception of the vasculature of the circumventricular organs. The results suggest that MECA-32 antigen expression is temporally and spatially correlated with the development of the blood brain barrier.

Journal ArticleDOI
TL;DR: The structural analysis of the 5 \ifmmode\times\else\texttimes\fi{} 1 phase finds an increased atomic volume in combination with a complex reconstruction pattern with sinusoidal shifts and vertical buckling that points towards a structural instability of the ferromagnetic fcc phase.
Abstract: Ultrathin fcc Fe films on Cu(100) up to 5 monolayers (ML) show a peculiar structural arrangement that is intimately linked with the ferromagnetic coupling within the film. Our structural analysis of the 5 \ifmmode\times\else\texttimes\fi{} 1 phase finds an increased atomic volume in combination with a complex reconstruction pattern with sinusoidal shifts and vertical buckling. The atomic configuration differs considerably from the bulklike structure of the interior of antiferromagnetic Fe films above 5 ML. This points towards a structural instability of the ferromagnetic fcc phase.

Journal ArticleDOI
TL;DR: Detailed anatomical findings are discussed in the context of absorptive mechanisms for the different macronutrients and the implication of enteroendocrine cells such as CCK-containing cells that may function as intestinal “taste cells”.
Abstract: Results from functional studies point to the importance of chemoreceptive endings in the duodenum innervated by vagal afferents in the regulation of gastrointestinal functions such as gastric emptying and acid secretion, as well as in the process of satiation. In order to visualize the vagal sensory innervation of this gut segment, vagal afferents were selectively labeled in vivo by injecting the lipophilic carbocyanine dye DiI into either the left or the right nodose ganglion of young adult rats. Thick cryostat sections or whole-mounted peels of muscularis externa or submucosa of formalinfixed tissue were analyzed with conventional and/or confocal microscopy. In the mucosa, many DiI-labeled vagal afferent fibers were found with terminal arborizations mainly between the crypts and the villous lamina propria. In both areas, vagal terminal branches came in close contact with the basal lamina, but did not appear to penetrate it so as to make direct contact with epithelial cells. Labeled vagal afferent fibers in the villous and cryptic lamina propria were found to be in intimate anatomical contact with fibrocyte-like cells that may belong to the class of interstitial cells of Cajal, and with small granular cells that might be granulocytes or histiocytes. Although our analysis was not quantitative, and considering that labeling was unilateral and not complete, it appears that the overall density of vagal afferent mucosal innervation was variable; many villi showed no evidence for innervation while other areas had quite dense networks of arborizing terminal fibers in several neighboring villi. Analysis of separate whole-mounted muscularis externa and submucosa peels revealed the presence of large bundles of labeled afferent fibers running within the myenteric plexus along the mesenteric attachment primarily in an aboral direction, with individual fibers turning towards the antimesenteric pole, and either penetrating into the submucosa or forming the characteristic intraganglionic laminar endings (IGLEs). Although the possibility of individual fibers issuing collaterals to myenteric IGLEs and at the same time to mucosal terminals was not demonstrated, it cannot be ruled out. These anatomical findings are discussed in the context of absorptive mechanisms for the different macronutrients and the implication of enteroendocrine cells such as CCK-containing cells that may function as intestinal “taste cells”.

Journal ArticleDOI
TL;DR: Careful pTNM classification allows a good estimation of the prognosis and can be considered the gold standard for any analysis of treatment results.
Abstract: The anatomic extent of tumor (TNM, pTNM) and, in case of treatment, the residual tumor status following treatment (residual tumor, or R classification) are the strongest predictors for outcome of patients with gastrointestinal cancer. The results of the pTNM and the R classifications depend on the methods used. In particular, the pN classification correlates with the number of nodes examined. The findings of micrometastases or isolated tumor cells in bone marrow should be indicated, and such cases must be analyzed separately from other metastatic cases. The same applies to patients with positive cytology in ascites fluid or peritoneal washings without gross involvement of the peritoneum. For the R classification the additional descriptors (conv), for conventional methods used, and (soph), for sophisticated, are recommended to indicate the methods used for classification. In general, long-term survival can be expected only after R0 resection (resection without residual tumor). The observed 5-year survival after R0 resection is 15% to 40% for esophageal carcinoma. 40% to 75% for gastric carcinoma, and 55% to 60% for colorectal carcinoma; the respective figures for R1 and R2 resections are only about 5% each. In R1 and R2 cases prognosis is determined primarily by the absence or presence of distant metastases, and pT and pN are of minor significance. After R0 resection there is a wide spectrum of prognoses. Careful pTNM classification allows a good estimation of the prognosis and can be considered the gold standard for any analysis of treatment results.

Journal ArticleDOI
TL;DR: A method for the off-line recognition of cursive handwriting based on hidden Markov models (HMMs) is described, which has an average correct recognition rate of over 98% on the word level and in experiments with cooperative writers using two dictionaries of I50 words each.

Journal ArticleDOI
TL;DR: The results favor the hypothesis that the persistence of antigen supports the maintenance of T cell memory and that dendritic cells are critically involved in this process.
Abstract: Upon infection with Leishmania major, a cause of human cutaneous leishmaniasis, mice of resistant strains are able to control the infection, with lesions resolving spontaneously. A long-lasting cell-mediated immunity protects them from reinfection. Nevertheless, small numbers of viable parasites persist in the lymph nodes of these mice. We have recently documented that, in addition to macrophages, epidermal Langerhans cells can ingest L. major. Furthermore, Langerhans cells have the unique ability to transport viable parasites from the infected skin to the draining lymph node for presentation to antigen-specific T cells and initiation of the cellular immune response. During migration, Langerhans cells develop into dendritic cells. In the present study, we analyzed whether dendritic cells support the persistence of parasites in immune hosts. Immunohistological studies and assays in vitro showed that in the lymph nodes of mice that have recovered from infection with L. major, both macrophages and dendritic cells harbor viable parasites. However, only dendritic cells were able to induce a vigorous T-cell immune response to L. major in vitro in the absence of exogenous antigen. Tracking experiments conducted in vivo suggested that the infected dendritic cells in the lymph nodes are derived from Langerhans cells that have emigrated from the skin. The data demonstrate that L. major-infected dendritic cells and macrophages in lymph nodes of immune animals represent long-term host cells, but only dendritic cells have the ability to present endogenous parasite antigen to T cells. Long-term infected dendritic cells may thus allow the sustained stimulation of a population of parasite-specific T cells, protecting the mice from reinfection. Our results favor the hypothesis that the persistence of antigen supports the maintenance of T cell memory and that dendritic cells are critically involved in this process.

Journal ArticleDOI
TL;DR: This novel approach to soot sizing exhibits several theoretical and technical advantages compared with the established combination of elastic scattering and LII, especially as it yields absolute sizes of primary particles without requiring calibration.
Abstract: The evaluation of the temporal decay of the laser-induced incandescence (LII) signal from soot particles is introduced as a technique to obtain two-dimensional distributions of particle sizes and is applied to a laminar diffusion flame. This novel approach to soot sizing exhibits several theoretical and technical advantages compared with the established combination of elastic scattering and LII, especially as it yields absolute sizes of primary particles without requiring calibration.

Journal ArticleDOI
TL;DR: Proteins binding at the interleukin-6 response element of the rat α2 macroglobulin gene were purified by a combination of chromatographic procedures including binding site-specific DNA-affinity chromatography as the principal step and activated Stat5 was detected in the nuclei of untreated control rats.

Journal ArticleDOI
TL;DR: A variety of tetracoordinate molecules which deviate fundamentally from tetrahedral symmetry have been surveyed anew by ab initio Becke3LYP density functional computations as discussed by the authors.
Abstract: A variety of tetracoordinate molecules which deviate fundamentally from tetrahedral symmetry have been surveyed anew by ab initio Becke3LYP density functional computations. These refine the earlier findings that electropositive substituents (i.e. metals) drastically reduce the planar-tetrahedral energy difference and favour planar “anti-van't Hoff” arrangements. The lowest lying energy minima of 1,1- and 1,2-dilithioethylene, and of 1,1-dilithiocyclopropane have planar tetracoordinate carbons. Planar geometries also are favoured by π acceptors. Owing to aromatic delocalization and the small CCspiroC angle, planar 2,3-diboraspiropentane (unlike diboracyclopropane itself) is a true minimum. Planar tetracoordinate carbons also are present in 3,3-dilithio-l,2-diboracyclopropane and in a C2B2H4 isomer.

Journal ArticleDOI
TL;DR: In this paper, the effects of various non-structural parameters, in particular those involved in the construction of the phase shifts, on the resulting structures of the clean Pt(111) and the Pt( 111)-p(2×2)-O surfaces were investigated.

Journal ArticleDOI
TL;DR: Under the given selection criteria for local therapy, radiation therapy yielded relapse-free and overall survival figures comparable to radical surgery and hyperfractionated split-course irradiation simultaneously with multidrug chemotherapy did not significantly improve local control or survival.
Abstract: Purpose : We present an update analysis of the multiinstitutional Ewing's sarcoma study CESS 86. Methods and Materials : From January 1986 through June 1991, 177 patients with localized Ewing's sarcoma of bone, aged 25 years or less, were recruited. Chemotherapy consisted of four 9-week courses of vincristine, actinomycin D, cyclophosphamide, and adriamycin (VACA) in low-risk tumors (extremity tumors < 100 cm 3 ), or vincristine, actinomycin D, ifosfamide, and adriamycin (VAIA) in high-risk tumors (central tumors and extremity tumors ≥ 100 cm 3 ). Local therapy was an individual decision in each patient and was either radical surgery (amputation, wide resection) or resection plus postoperative irradiation with 45 Gy or definitive radiotherapy with 60 Gy (45 Gy plus boost). Irradiated patients were randomized concerning the type of fractionation in either conventional fractionation (once daily 1.8-2.0 Gy, break of chemotherapy) or hyperfractionated split-course irradiation simultaneously with the VACA/VAIA chemotherapy (twice daily 1.6 Gy, break of 12 days after 22.4 Gy and 44.8 Gy, total dose and treatment time as for conventional fractionation). For quality assurance in radiotherapy, a central treatment planning program was part of the protocol. Results : Forty-four patients (25%) received definitive radiotherapy ; 39 (22%) had surgery, and 93 (53%) had resection plus postoperative irradiation. The overall 5-year survival was 69%. Thirty-one percent of the patients relapsed, 30% after radiotherapy, 26% after radical surgery, and 34% after combined local treatment. The better local control after radical surgery (100%) and resection plus radiotherapy (95%) as compared to definitive radiotherapy (86%) was not associated with an improvement in relapse-free or overall survival because of a higher frequency of distant metastases after surgery (26 % vs. 29% vs. 16%). In irradiated patients, hyperfractionated split-course irradiation and conventional fractionation yielded the same results (5-year overall survival of definitively irradiated patients 63% after conventional fractionation and 65% after hyperfractionation ; relapse-free survival 53% vs. 58% ; local control 76% vs. 86%, not significant). The six local failures after radiotherapy did not correlate with tumor size or response to chemotherapy. Radiation treatment quality (target volume, technique, dosage) was evaluated retrospectively and was scored as unacceptable in only 1 out of 44 patients (2%) with definitive radiotherapy. Grade 3-4 complications developed in 4 out of 44 (9%) patients after definitive radiotherapy. Conclusions : Under the given selection criteria for local therapy, radiation therapy yielded relapse-free and overall survival figures comparable to radical surgery. Hyperfractionated split-course irradiation simultaneously with multidrug chemotherapy did not significantly improve local control or survival.

Journal Article
TL;DR: Accumulation of locally produced PEX material in the JCT, followed by dysfunction of endothelial cells and disorganization of JCT and Schlemm's canal, appear to be causative factors in the development of a special type of secondary open-angle glaucoma in PEX syndrome.
Abstract: Purpose. To test the hypothesis that glaucoma in eyes with pseudoexfoliation (PEX) syndrome results from blockage of the outflow channels by PEX material, melanin granules from the iris pigment epithelium, or both, and to determine the origin of intratrabecular PEX material. Methods. Trabecular meshwork tissue was obtained from five surgically enucleated eyes with PEX glaucoma, ten autopsy eyes with PEX syndrome without evidence of glaucoma, and six age-matched control eyes. Morphometric methods were used to measure the percentage area occupied by open spaces, cells, plaque material, PEX material, and melanin granules on electron micrograph montages of the entire filtration area and the juxtacanalicular tissue (JCT) area. Results. Independent of the presence of glaucoma, most PEX deposits were located in the JCT adjacent to the inner and outer walls of Schlemm's canal, as well as in the uveal meshwork. Although ultrastructural evidence indicates the local production of PEX fibers in the JCT by endothelial and connective tissue cells, PEX material in the uveal meshwork is derived partly from the aqueous humor. A significant correlation could be established between the presence of glaucoma and the amount of PEX material in both the filtration area and the JCT, the average thickness of the JCT, and the mean cross-sectional area of Schlemm's canal. No significant correlation existed, however, between glaucoma status and the concentration of melanin granules or plaque material, and the cellularity. Conclusion. In addition to a mechanical obstruction by PEX material of exotrabecular origin, the apparent production of PEX material by trabecular cells may be principally responsible for glaucoma development. Accumulation of locally produced PEX material in the JCT, followed by dysfunction of endothelial cells and disorganization of JCT and Schlemm's canal, appear to be causative factors in the development of a special type of secondary open-angle glaucoma in PEX syndrome. Invest Ophthalmol Vis Sci. 1995 ;36 :1750-1764.

Journal ArticleDOI
TL;DR: The data show that local restriction of parasites in the pre‐T cell phase of the infection is mediated by the innate immune system and suggest that this function plays an important role in the development of a protective T cell response.
Abstract: We investigated the early spread of Leishmania major in various mouse strains. In BALB/c mice, which are extremely vulnerable to L. major infection, the parasites disseminated within 10-24 h from the site of subcutaneous footpad infection in to the popliteal lymph node, spleen, lung, liver and bone marrow. Application of recombinant (r)IL-12 prior to infection prevented the early dissemination of parasites into visceral organs and the animals healed the infection. In three mouse strains tested, C57BL/6, CBA/J and C3H/HeJ, which are all resistant to L. major infection, the parasites remained localized in the footpad and in the draining LN for 3 days without evidence of dissemination. In C57BL/6 mice, depletion of NK1.1+ cells or neutralization of interferon (IFN)-gamma prior to infection led to rapid parasite spreading with kinetics similar to those seen in susceptible animals. Depletion of either CD4+ or CD8+ T cells in vivo prior to infection did not alter the kinetics of dissemination in any mouse strain tested. Experiments with severe-combined immunodeficient mice provided further evidence that parasite containment depends on natural killer cells and IFN-gamma, but is independent of T cells. The finding that all resistant mouse strains restrict the spread of the parasites within the first 24 h after infection strongly suggests that early parasite containment is closely associated with a resistant phenotype. The data show that local restriction of parasites in the pre-T cell phase of the infection is mediated by the innate immune system and suggest that this function plays an important role in the development of a protective T cell response.


Journal ArticleDOI
TL;DR: Serum levels of soluble ICAM- 1, VCAM-1, P-selectin, and, to a lesser degree, E- selectin correlate well with their in situ activity and with clinical disease activity, and provide a useful tool for the characterization of disease stage, progression, and prognosis in patients with systemic sclerosis.
Abstract: Objective. To correlate serum levels of the soluble adhesion molecules intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), E-selectin, and P-selectin with (a) clinical disease activity and progression and (b) the in situ expression and distribution of these adhesion molecules in lesional skin, in patients with systemic sclerosis (SSc). Methods. Serum samples from 12 SSc patients and 36 healthy controls were examined by enzymelinked immunosorbent assay. Immunohistologic staining was carried out on cryostat sections of lesional skin. Results. Patients whose SSc was in the early inflammatory stage or who had prominent disease progression showed elevated serum levels of soluble adhesion molecules. Serum levels correlated positively with the expression of these molecules on endothelial cells and fibroblasts in lesional skin. Conclusion. Serum levels of soluble ICAM-1, VCAM-1, P-selectin, and, to a lesser degree, E-selectin correlate well with their in situ activity and with clinical disease activity. These parameters therefore provide a useful tool for the characterization of disease stage, progression, and prognosis in SSc.