Plasma cells (PCs) are the final B-cell differentiation stage. Recent evidence reveals relevant functional differences within the PC compartment. In rodents, early PCs formed in secondary lymphoid tissues show enhanced apoptosis and short life span, whereas PCs present in a final destination organ, such as the bone marrow (BM), have reached a stable prolonged survival state. BM PCs arrive at this organ as a circulating precursor whose cellular nature remains uncertain. An initial aim of this study was to characterize this circulating cell. We hypothesized that antibody-secreting cells detectable in the human blood after immunization might be a candidate precursor. These cells were obtained from the blood of volunteers immunized 6 days earlier with tetanus toxoid (tet), and they were unambiguously identified as PCs, as demonstrated by their expression of the CD38 h phenotype, by morphology, by immunoglobulin (Ig) intracytoplasmic staining, and by IgG-tet-secreting capacity in vitro. In addition, by using the common CD38 h feature, human PCs from tonsil (as a possible source of early PCs), from blood from tet-immunized donors (as the putative precursors of BM PCs), and from BM (as a deposit organ) have been purified and their phenotypes compared. The results show that a variety of differentiation molecules, proteins involved in the control of apoptosis, the B-cell transcription factors, positive regulatory domain I-binding factor 1/B lymphocyteinduced maturation protein 1 and B cellspecific activating protein and, at least partially, the chemokine receptor CXCR4 were expressed by human PCs following a gradient of increasing maturity in the direction: tonsil3blood3BM. However, PCs from these different organs showed a local pattern of adhesion molecule expression. These observations are dis- IntroductionPlasma cells (PCs) are the morphologically well-defined cellular end point of the B-lymphocyte differentiation sequence, and, as such, they exhibit biochemical and structural features indicative of their full commitment to the synthesis and secretion of antibody (Ab). Therefore, PCs are ultimately responsible for the humoral immune response. Experiments in rodents have revealed that, soon after antigen (Ag) entry, PCs are formed in inductive territories of the secondary lymphoid tissue, initially within Ag-activated foci occurring in the T-cell areas of draining lymphoid tissue and, if the Ag persists, they are also generated in germinal centers (GCs). [1][2][3] After this early phase, the number of PCs falls drastically in these areas and they start accumulating in final deposit locations, namely the bone marrow (BM) and the lamina propria (LP), for systemic and mucosal humoral responses, respectively. [4][5][6] PCs present in the deposit organs are not formed in situ, but they derive from close precursors generated in distant lymphoid organs as a result of Ag stimulation, which migrate into these areas through the circulation. 7,8 The nature of this PC precursor has not been fully clarified. It is well established...
Extrapulmonary tuberculosis (TB) represents approximately 15% of all TB infections. It is difficult to diagnose on the basis of imaging characteristics and clinical symptoms, and biopsy is required in many cases. Radiologists must be aware of the imaging findings of extrapulmonary TB to identify the condition in high-risk patients, even in the absence of active pulmonary infection. In extrapulmonary TB, the lymphatic system is most frequently affected. The presence of necrotic lymph nodes and other organ-specific imaging features increases the diagnostic probability of extrapulmonary TB. Disseminated infection and central nervous system involvement are the most frequent manifestations in immunosuppressed patients. Renal disease can occur in immunocompetent patients with very long latency periods between the primary pulmonary infection and genitourinary involvement. In several cases, gastrointestinal, solid-organ, and peritoneal TB show nonspecific imaging findings. Tuberculous spondylitis is the most frequent musculoskeletal manifestation. It is usually diagnosed late and affects multiple vertebral segments with extensive paraspinal abscess. Articular disease is the second most frequent musculoskeletal manifestation, and synovitis is its predominant imaging finding. ©
Purpose-Seeks to evaluate the link between task and relationship conflict, and their influence on some employees' affective reactions such as satisfaction, wellbeing, and propensity to leave a job; and to analyse the mediated and moderated role of relationship conflict. Design/methodology/approach-The study involved 169 employees from six service organizations (hotels) in Andalusia (Spain). A questionnaire was used containing different measures: task and relationship conflict, wellbeing, job satisfaction, and propensity to leave the job. Findings-The two types of conflict have different consequences. Data show that relationship conflict is negatively associated with affective reactions, while task conflict does not relate directly to affective reactions in a predictable way; relationship conflict has a positive influence on the desire to leave the current job, while task conflict does not affect it negatively; the interactive effect of relationships and task conflict shows that this interaction contributes substantially to predict the propensity to leave the current job; and relationship conflict mediates in the link between task conflict and affective reactions. Research limitations/implications-A high level of task conflict may backfire by boosting relationship conflict as well, thus having a negative effect on affective reactions. Thus some conclusions can be drawn with a view to improving conflict management in teams. First an attempt must be made to understand the type of conflict that is taking place. Second, managers should encourage open discussion of task-related issues. Third, special attention should be paid to the level of each conflict because of its interactive effects on some affective outcomes. Thus, in spite of the generally beneficial effects associated with task conflict, the intensification of task-related conflict may backfire when interacting with dysfunctional affective-dissent. Originality/value-Serves too analyze the mediated and moderated role of relationship conflict and to test the role of types of conflict on affective reactions such as wellbeing and propensity to leave the job. Keywords Conflict, Organizational conflict, Job satisfaction, Spain Paper type Research paper One of the most outstanding aspects of conflict is that it is practically intrinsic to the life and dynamics of teams. Conflict is present in interpersonal relations (Pruitt and Carnevale, 1993), in intragroup and intergroup relations (Jehn, 1995), in strategic decision-making (Amason, 1996
To define the clinical and immunologic pattern of expression of Sjögren syndrome (SS) associated with chronic hepatitis C virus (HCV) infection, we conducted a multicenter study aiming to collect a large number of patients with SS and HCV infection. Inclusion criteria were the fulfillment of at least 4 of the classification criteria for SS proposed by the European Community Study Group and repeated positive HCV serology, confirmed by recombinant immunoblot assay and/or detection of serum HCV-RNA by polymerase chain reaction. One hundred thirty-seven patients were included (104 female and 33 male; mean age, 65 yr). Seventy-nine (58%) patients presented a systemic process with diverse extraglandular manifestations, with articular involvement (44%), vasculitis (20%), and neuropathy (16%) being the most frequent features observed. The main immunologic features were antinuclear antibodies (65%), hypocomplementemia (51%), and cryoglobulinemia (50%). Cryoglobulins were associated with a higher frequency of cutaneous vasculitis, rheumatoid factor, and hypocomplementemia. Thirty-two (23%) patients had positive anti-Ro/SS-A and/or anti-La/SS-B antibodies; these patients were predominantly women and had a higher prevalence of some extraglandular features and a lower frequency of liver involvement. Nineteen (14%) patients developed neoplasia, with hematologic neoplasia (8 cases) and hepatocellular carcinoma (6 cases) being the most frequent types. Eighty-five percent of SS-HCV patients also fulfilled the recently proposed 2002 classification criteria for SS. In conclusion, HCV-associated SS is indistinguishable in most cases from the primary form using the most recent set of classification criteria. Chronic HCV infection should be considered an exclusion criterion for the classification of primary SS, not because it mimics primary SS, but because the virus may be implicated in the development of SS in a specific subset of patients. We propose the term "SS secondary to HCV" when these patients fulfill the 2002 classification criteria for SS.
The Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index is a validated instrument specifically designed to ascertain damage in SLE; this instrument has been applied mainly to Caucasians and African-American SLE patients. The objective of this study was to assess damage using the SLICC/ACR Damage Index in Mexican SLE patients. The SLICC/ACR Damage Index was applied to 210 consecutive SLE patients with disease of variable duration. The SLICC/ACR Damage Index was assessed by review of hospital clinical records, interview and physical examination. One hundred and seventeen (55.5%) patients had some damage. The proportion of patients with damage increased significantly with disease duration (33% at 1-60 months, 66% at 61-120 months and 70% at > or = 121 months, P < 0.001). The main organ systems involved were musculoskeletal (osteonecrosis), neuropsychiatric (neuropathy, seizures), gonadal (amenorrhea prior to age 40 years), ocular (cataracts), renal (glomerular filtration < 50%) and peripheral vascular (permanent damage by venous thrombosis). Damage was frequent, increased over time, particularly for ocular, renal, musculoskeletal and gonadal. Patients who experienced damage were older, had a longer disease duration, a greater number of ACR criteria at diagnosis, and were more likely to have renal involvement and antibodies to dsDNA. The damage occurred in many different domains and started to develop early after disease onset. Mexican patients had more peripheral vascular and gonadal involvement compared with published data from non-Hispanic SLE populations.
The online version of this article has a Supplementary Appendix. BackgroundIn hematology there has recently been increasing interest in inorganic polyphosphate. This polymer accumulates in platelet granules and its functions include modulating various stages of blood coagulation, inducing angiogenesis, and provoking apoptosis of plasma cells. In this study we evaluated the characteristics of intracellular polyphosphate in myeloma cell lines, in primary myeloma cells from patients, and in other human B-cell populations from healthy donors. Design and MethodsWe have developed a novel flow cytometric method for detecting levels of polyphosphate in cell populations. We also used confocal microscopy and enzymatic analysis to study polyphosphate localization and characteristics. ResultsWe found that myeloma plasma cells contain higher levels of intracellular polyphosphate than normal plasma cells and other B-cell populations. Localization experiments indicated that high levels of polyphosphate accumulate in the nucleolus of myeloma cells. As the principal function of the nucleolus involves transcription of ribosomal DNA genes, we found changes in the cellular distribution of polyphosphate after the inhibition of nucleolar transcription. In addition, we found that RNA polymerase I activity, responsible for transcription in the nucleolus, is also modulated by polyphosphate, in a dose-dependent manner. ConclusionsOur results show an unusually high accumulation of polyphosphate in the nucleoli of myeloma cells and a functional relationship of this polymer with nucleolar transcription. Haematologica 2012;97(8):1264-1271. doi:10.3324/haematol.2011 This is an open-access paper. Myeloma cells contain high levels of inorganic polyphosphate which is associated with nucleolar transcription ABSTRACT© F e r r a t a S t o r t i F o u n d a t i o n
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