Mechanisms regulating IgA class-specific immunoglobulin production in murine gut-associated lymphoid tissues. I. T cells derived from Peyer's patches that switch sIgM B Cells to sIgA B cells in vitro

To explore mechanisms of T cell regulation governing mucosal IgA immune response, concanavalin A-induced cloned T cell lines from Peyer's patches (PP) as well as spleen were established. The cloned cell lines expressed Thy- 1.2(+), Lyt-l(+)2(-) and were radioresistant (1,500 rad). The capacity of the cloned T cells to regulate Ig synthesis was determined by measuring their effect on lipopolysaccharide (LPS)-induced polyclonal Ig synthesis by PP B cells. In initial studies Ig secreted by B cells was determined by double antibody radioimmunoassay. LPS in the absence of cloned T cells induced abundant amounts of IgM (average 8,860 ng/2 × 10(5) B cells) and IgG (average 1,190 ng/2 × 10(5) B cells), but little or no IgA. The addition of PP cloned T cells markedly suppressed production of IgM (88 percent at the highest T/B cell ratio, 4:1), but the addition of spleen cloned T cells suppressed only a little or not at all. IgG production was inhibited by both PP and spleen T clone cells (70 percent at the 4:1 T/B ratio), wheras IgA synthesis was enhanced by both clones, but only to a limited degree. In subsequent studies the expression of class-specific surface Ig (sIg) and cytoplasmic Ig (cIg) on/in unseparated PP B cells as well as Ig class- specific PP B cells and spleen B cells during culture with or without the cloned T cells was determined by immunofluorescence. The major findings were as follows: (a) Compared with unseparated B cell cultures and cultures of purified sIgM B cells derived from PP containing LPS alone, cultures containing LPS and PP cloned T cells showed a marked decrease in cIgM-, sIgG-, and cIgG-expressing cells that was accompanied by a striking increase in sIgA-bearing, but not cIgA-containing, cells. In contrast, unseparated B cell cultures and cultures of purified sIgM B cells derived from PP containing LPS and spleen cloned T cells did not show any increase in sIgA- bearing cells. (b) Compared with purified sIgG-bearing PP B cell cultures containing LPS alone, purified sIgG-bearing PP B cell cultures containing both LPS and PP cloned T cells showed no substantial change in sIgG- or cIgG- expressing cells, and no sIgA- or cIgA- expressing cells appeared. (c) Compared with sIgA-bearing PP B cell cultures containing LPS alone, purified sIgA-bearing PP B cell cultures containing both LPS and PP cloned T cells showed no increased proliferation, and cIgA cells did not occur. Cultures of purified sIgM B cells derived from spleen containing LPS and PP cloned T cells showed qualitatively similar changes. From these results we conclude that PP cloned T cells induced class-specific switching from sIgM- to sIgA- bearing B cells, whereas spleen cloned T cells lacked this property, although they may have induced an IgM {arrow} IgG or intersubclass IgG switch. These processes seem to be in part tissue dependent. Furthermore, the PP switch T cells appear to operate as true switch cells, which govern the pathway of DNA recombination events, rather than as classical helper cells, which act to expand already differentiated cells. Finally, these switch T cells probably account for the fact that PP are an important source of IgA B cells and also a major site of IgA heavy chain class switching during gut-associated mucosal B cell proliferation and differentation

Long-term peritoneal dialysis and encapsulating peritoneal sclerosis in children

Encapsulating peritoneal sclerosis (EPS) is the most serious complication of long-term peritoneal dialysis (PD), with a mortality rate that exceeds 30%. There have been many reports of the incidence of EPS being strongly correlated to the duration of PD. Patients on PD for longer than 5 years, and especially those receiving this treatment for more than 8 years, should undergo careful and repeated surveillance for risk factors associated with the development of EPS. The development of ultrafiltration failure, a high dialysate/plasma creatinine ratio, as determined by the peritoneal equilibration test, peritoneal calcification, a persistently elevated C-reactive protein level, and severe peritonitis in patients on PD for longer than 8 years are signals that should prompt the clinician to consider terminating PD as a possible means of preventing the development of EPS. The impact of the newer, biocompatible PD solutions on the incidence of EPS has not yet been determined

Response of angina and ischemia to long-term treatment in patients with chronic stable angina: A double-blind randomised individualized dosing trial of nifedipine, propranolol and their combination

AbstractSeventy-four patients with chronic stable mild angina, mild coronary artery disease (83% had one- or two-vessel disease) and normal left ventricular function were studied to measure the response of treadmill exercise performance and painful and silent ischemia in the ambulatory setting to randomly assigned treatment with nifedipine or propranolol and their combination; titration to maximal tolerated dosages was performed in doubleblind manner.At 3 months both nifedipine and propranolol reduced the weekly angina rate (p < 0.05); during treadmill exercise testing, increases (p < 0.05) were noted in time to angina and total exercise time and decreases in maximal ST depression at the end of exercise. There were no differences between the responses to nifedipine and propranolol and no significant additional changes were seen after another 3 months of therapy. The combination of nifedipine and propranolol reduced the number of patients with angina on exercise treadmill testing from 64% to 38% (p < 0.05).During ambulatory electrocardiographic monitoring before treatment, there were 1.4 ± 2.4 (mean ± SD) episodes/24 h of painful ischemia and a very low silent ischemia frequency: mean 1.1 ± 2.7 episodes/24 h, mean duration 16 ± 25 min/24 h. Treatment with propranolol and nifedipine resulted in reduction of episodes and duration of painful and painless ischemia; approximately 77% of patients were free of all ischemic episodes.It is concluded that patients with chronic stable mild angina have a low incidence of silent ischemia. Nifedipine or propranolol alone, titrated to individualized maximally tolerated dosages, are equally effective in long-term control of painful and painless ischemia, anginal episodes and exercise-induced ischemia. Combination therapy further reduced only exercise-induced angina and maximal exercise-induced ST depression

AlGaAs/GaAs transverse junction stripe lasers with distributed feedback

Transverse junction stripe (TJS) lasers with periodic feedback were fabricated in two geometries. An interferometric and wet chemical etching technique was used to create a feedback grating across the entire pumping region for the distributed feedback (DFB) TJS laser and to create the separate distributed Bragg reflectors/DBR) for the TJS/DBR laser. The TJS/DFB laser was a double heterostructure device grown by liquid phase epitaxy (LPE) and had a third order grating etched in the top ALO.2GaO.8As layer. The grating was buried by growing an ALO.35GaO.65As layer on the grating by metal organic chemical vapor deposition (MO-CVD). The TJS/DBR laser was also fabricated in an LPE double heterostructure. The top AlGaAs layer was thinned to 0.1 micron over more than half of the laser so that the grating would be close to the GaAs active layer and optical field. Single mode operation in both configurations was obtained. The thermal shift of the laser wavelength in both cases was less than 1 Angstrom/deg K, compared to the 3 Angstrom/deg K shift of the spontaneous emission peak

Attribute-aware Semantic Segmentation of Road Scenes for Understanding Pedestrian Orientations

Semantic segmentation is an interesting task for many deep learning researchers for scene understanding. However, recognizing details about objects' attributes can be more informative and also helpful for a better scene understanding in intelligent vehicle use cases. This paper introduces a method for simultaneous semantic segmentation and pedestrian attributes recognition. A modified dataset built on top of the Cityscapes dataset is created by adding attribute classes corresponding to pedestrian orientation attributes. The proposed method extends the SegNet model and is trained by using both the original and the attribute-enriched datasets. Based on an experiment, the proposed attribute-aware semantic segmentation approach shows the ability to slightly improve the performance on the Cityscapes dataset, which is capable of expanding its classes in this case through additional data training

Complete Genome Sequence and Comparative Analysis of the Fish Pathogen Lactococcus garvieae

Lactococcus garvieae causes fatal haemorrhagic septicaemia in fish such as yellowtail. The comparative analysis of genomes of a virulent strain Lg2 and a non-virulent strain ATCC 49156 of L. garvieae revealed that the two strains shared a high degree of sequence identity, but Lg2 had a 16.5-kb capsule gene cluster that is absent in ATCC 49156. The capsule gene cluster was composed of 15 genes, of which eight genes are highly conserved with those in exopolysaccharide biosynthesis gene cluster often found in Lactococcus lactis strains. Sequence analysis of the capsule gene cluster in the less virulent strain L. garvieae Lg2-S, Lg2-derived strain, showed that two conserved genes were disrupted by a single base pair deletion, respectively. These results strongly suggest that the capsule is crucial for virulence of Lg2. The capsule gene cluster of Lg2 may be a genomic island from several features such as the presence of insertion sequences flanked on both ends, different GC content from the chromosomal average, integration into the locus syntenic to other lactococcal genome sequences, and distribution in human gut microbiomes. The analysis also predicted other potential virulence factors such as haemolysin. The present study provides new insights into understanding of the virulence mechanisms of L. garvieae in fish