Bone marrow origin of mucosal mast cells

Infection with the intestinal parasite Nippostrongylus brasiliensis stimulates an accumulation of mucosal mast cells (MMC) in the villi of the small intestine of normal but not athymic or W/Wv anemic mice. W/Wv mice are congenitally deficient in both MMC and skin and connective tissue mast cells (CTMC). Athymic mice have normal or elevated numbers of CTMC but are severely deficient in MMC. CTMC derive from the bone marrow. To determine the origin of MMC, athymic and W/Wv mice were given various hematopoietic or lymphoid tissues from normal littermate or beige mice and the MMC response to N. brasiliensis infection was evaluated. The MMC defect in athymic mice was repaired by grafts of thymus cells, thymus gland, or spleen cells, but not by bone marrow cells or anti-Thy 1-treated bone marrow or spleen cells. The MMC and CTMC defects of W/Wv mice were repaired by grafts of bone marrow, spleen cells, or anti-Thy 1-treated bone marrow or spleen cells. Neither the MMC nor the CTMC defect in W/Wv mice was repaired by grafts of thymus cells or thymus glands. These results indicate the following, MMC, like CTMC, derive from the bone marrow and not from the thymus. MMC require a thymic influence for development. Athymic mice possess bone marrow precursors for both MMC and CTMC but lack a thymus-dependent component necessary for MMC development. W/Wv mice lack both MMC and CTMC mast cell precursors but possess the thymus-dependent component required for MMC development.     

Dermatoglyphic features in Prader-Willi syndrome with respect to chromosomal findings

Dermatoglyphic findings were compared in 38 Prader-Willi syndrome (PWS) patients and 270 normal controls. Twenty-one of the PWS patients had an interstitial deletion of the proximal long arm of chromosome 15 and seventeen PWS cases had normal chromosomes. Findings in PWS are not diagnostic but do show some consistent deviations that can be used in the clinical evaluation of PWS patients. These include a displacement of the axial triradius away from the normal proximal position, an excess of whorls primarily on the thumbs, radial termination of the palmar A mainline, and lack of arches on the big toe. Deletion PWS patients were much more homogeneous than non-deletion cases with respect to plantar patterns. The previously reported deficit of plantar pattern intensity was restricted only to deletion PWS and was characterized by a lack of plantar interdigital II-IV patterns with almost exclusively hallucal distal loops.     

Primary school children: access to toilets

Aim: Most children are continent of urine by the time they are in primary school. Balanced micturition and paradoxically dysfunctional voiding (DV) are acquired behaviour. Children need easy access to toilets at school, to comply with timed voiding which is part of the treatment for DV. This study investigated children's access to primary school toilets in Auckland. Methods: A questionnaire was sent to 97 primary schools listed on the New Zealand ministry of education (MoE) website for the Auckland region. Information regarding the school decile rating, population, rota, toilet facilities and toilet policy was requested. Six randomly selected schools were visited to verify the facilities available there. Results: Eighty‐four percent of the schools in our sample complied with the prescribed statutory minimum for both boys and girls toilets. There was a median ratio of 11 children per facility. The median duration to use a facility during the first recess was 2 min. Conclusion: In general, the toilet facilities and utilization ratios in primary schools in the Auckland region appear to provide a healthy environment for urination. Schools must be encouraged to draft and adhere to a toilet policy to ensure a uniform toilet environment.     

Seasonal exacerbation of eosinophilic esophagitis histologic activity in adults and children implicates role of aeroallergens

Background

Disease activity may correlate with environmental aeroallergen exposure in eosinophilic esophagitis. The association between seasons and flares of eosinophilic esophagitis (EoE) histologic activity has not been extensively studied.

Peripheral Immunotype Correlates with Minimal Residual Disease Status and Is Modulated by Immunomodulatory Drugs in Multiple Myeloma

Data indicate reversal of immune dysfunction with active treatment; however, the precise contribution of specific immune effector and immune suppressor components to achieve a minimal residual disease (MRD) state and immunomodulatory drug–mediated immunomodulatory effects in multiple myeloma (MM) patients remains poorly understood. In this prospective proof-of-principle study we sought to determine the dynamic alterations in natural killer (NK), NK-T, and T cells, including maturation and activating/inhibitory repertoire associated with MRD^pos versus MRD^neg status after autologous stem cell transplantation (ASCT) and during lenalidomide-based maintenance therapy. Of the 46MM patients enrolled, 36 had bone marrow MRD assessment 60+ days post-ASCT, 30 had longitudinal blood immunotyping during maintenance (pretherapy and after cycles 1, 3, and 6), and 20 had both MRD assessment and longitudinal immunotyping. Multicolor flow cytometry was used for MRD and immunotyping. Although the absolute number of NK cells was significantly lower in patients with MRD^pos response, phenotypically NK cells in these patients displayed higher expression of activating receptors KIRDS4 and decreased expression of inhibitory molecules NKG2A compared with the MRD^neg group. Furthermore, we observed significantly lower frequencies of T cells displaying KIR3DL1 in MRD^pos versus MRD^neg patients. Longitudinal immunotyping during lenalidomide maintenance showed loss of mature NK effector function, augmentation of NK-T effector function, and acquisition of PD1 independent anergic state. Our findings also suggest skewing of T cells toward an exhausted state during the maintenance phase in MRD^pos patients. Put together, these observations provide a distinctive signature for MRD^neg and MRD^pos groups. These data support exploration of immune profiling in prospective clinical trials according to MRD-defined responses to identify patients that may benefit from maintenance intensification/modification or maintenance withdrawal.     

Granulocyte/macrophage colony stimulating factor. A potent activation signal for mature macrophages and monocytes

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a well-characterized hematopoietic growth factor. Recently, using purified recombinant-derived material, we have found that GM-CSF is also a potent activator of mature functional macrophages. Thus, we have found that exogenous GM-CSF augments the primary plaque-forming response to sheep red blood cells and that this effect is due to upregulation of Ia antigen expression and interleukin 1 production by the macrophages. We also show that GM-CSF inhibits the replication of Trypanosoma cruzi in cultured peritoneal macrophages and causes an accelerated clearance of Salmonella typhimurium from the peritoneal cavity of mice. These data indicate that GM-CSF is a multifunctional molecule stimulating both hematopoiesis and mature macrophage function.     

Thiol proteinase expression and pathogenicity of Entamoeba histolytica.

Expression of the 56-kilodalton (kDa) neutral thiol proteinase has been shown to correlate with the potential of clinical isolates of Entamoeba histolytica to produce invasive disease. A 56-kDa band was identified by gelatin substrate gel electrophoresis in 10 of 10 isolates from patients with colitis or amebic liver abscesses, but in only 1 of 10 isolates from asymptomatic patients. Pathogenic isolates appear capable of releasing significantly larger quantities of the proteinase, as measured by cleavage of a synthetic peptide substrate, ZRR-AMC (benzyloxy-carbonyl-arginine-arginine-4-amino-7-methylcoumarin). We have also shown that the proteinase is released during the course of clinical invasive amebic disease, as demonstrated by the presence of circulating antibodies detectable by enzyme-linked immunosorbent assay. These studies support the importance of the 56-kDa thiol proteinase in the pathogenesis of invasive amebiasis.     

Differential Regulation of Bax, Bcl-2, and Bcl-X Proteins in Focal Cortical Ischemia in the Rat

Focal ischemia in the parietal cortex of the rat results in massive neuronal death in the infarct zone and penumbra between 12 hours and 6 days after photothrombosis. To examine a possible role of Bcl-2 family proteins in this process of cell death, we investigated their expression by immunoblot assays and immunocytochemistry, and correlated expression patterns with TUNEL as well as morphological signs indicative of apoptosis. In the center of the lesion Bax immunostaining was increased in many degenerating neurons between 4 hours and 3 days after the induction of photothrombosis. At all time points examined, Bcl-2 and Bcl-X protein levels were markedly reduced in injured neurons as compared to the unlesioned side. At the border of the ischemic lesion, two areas were distinguished: 1 – 2 days after induction of photothrombosis, pyknotic cells located immediately adjacent to the lesion core displayed nuclear Bcl-X and Bax immunoreactivity. In contrast, large, morphologically intact neurons located more towards the healthy brain parenchyma displayed an increase in cytoplasmic Bcl-2 and Bcl-X proteins. Double staining for each of the Bcl-2 family proteins and TUNEL revealed that DNA strand breaks and nuclear fragmentation seen in cells located in the lesion core were often associated with increased levels of Bax, but not with elevated Bcl-2 or Bcl-X protein levels, suggesting a role for Bax in the induction of apoptotic death in these cells. The upregulation of Bcl-2 and Bcl-X expression in surviving neurons close to the penumbra might reflect an active survival mechanism that protects these neurons from cell death following a sublethal insult.