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The basics of quality management with a focus on continuous quality improvement (CQI) will be highlighted in this chapter. Quality, total quality management, and CQI will be defined, and an easy-to-implement CQI model will be presented. [ABSTRACT FROM AUTHOR]

It is essential for nephrology nurses to understand the basics of iron function and the importance of maintaining iron balance in their patients. Iron forms the cornerstone of oxygen delivery in the body and is the most essential nutrient for the building of healthy erythrocytes. Given the vital importance of iron, the body has devised elaborate and tightly controlled mechanisms to transport iron to the bone marrow for hemoglobin production, recycle iron from dying erythrocytes, and prevent iron loss. In the healthy individual, daily iron intake needs are very small, and sufficient iron is easily absorbed from the duodenum. In patients on hemodialysis, this iron balance is dramatically altered due to blood loss, inflammation, and the use of erythropoiesis-stimulating agents. This article discusses the basics of iron physiology and the mechanisms by which iron is moved throughout the body and made available for developing erythrocytes. The ways in which iron balance is altered in the patient on hemodialysis and the most effective strategies to replete iron stores and maintain iron balance through the use of intravenous iron are also reviewed. [ABSTRACT FROM AUTHOR]

Objectives: Systemic sclerosis (SSc) is a chronic connective tissue disease characterized by vascular damage, autoimmunity, and excessive collagen deposition. Despite advances in disease-specific treatment of other rheumatologic diseases, disease-targeted treatment in SSc continues to be elusive. In this review, our goal was to place the contemporary immunobiology of SSc in the perspective of clinical medicine.Methods: We performed a PubMed search for the period from 1989 to 2007, using the keyword, 'systemic sclerosis,' resulting in a total of 9099 publications, including 1252 reviews. Articles were then selected based on their discussion of recent advances in the elusive pathogenesis of SSc. A final total of 259 articles were chosen for the review.Results: The SSc hallmarks of vascular damage, immunologic activation, and collagen deposition can be traced to 4 major factors: T-cells, fibroblasts, B-cells, and cytokines/chemokines. T-cells are a major component of the infiltrate in skin and lung, exhibiting increased expression of activation markers and showing signs of antigen-driven expansion. Preliminary data indicate that induction of oral tolerance with collagen, a target of SSc T-cell responses, is associated with clinical benefits. Although this suggests that T-cells participate in the pathogenesis of SSc, their precise role and antigen specificity largely remain to be elucidated. Defective numbers and functions of certain T-cell subsets, such as natural killer and [gamma delta] T-cells, may be involved in the failure to maintain tolerance. Other data suggest that [gamma delta] T-cells may themselves be effector cells in endothelial cell cytotoxicity. There are several lines of evidence for a pathogenic role of B-cells in SSc, in particular, through the production of autoantibodies. Antibody-dependent cell-mediated cytotoxicity is a primary pathogenic event in an animal model of SSc and is likely to be involved in human SSc. Nonetheless, there is as yet no convincing evidence for the pathogenicity of SSc-specific antibodies. SSc fibroblasts exhibit a specific phenotype characterized not only by excessive collagen production but also by increased responsiveness to and production of cytokines and chemokines. This phenotype is induced by a complex network of cytokines and chemokines but appears to be maintained in the absence of exogenous stimuli via the autocrine production of some of these factors by SSc fibroblasts themselves, particularly transforming growth factor, platelet-derived growth factor, monocyte chemoattractant protein 1, and interleukin-1.Conclusions: Significant variations in laboratory data among patients suggest that the pathology reflects a heterogeneous disease. Nonetheless, the possibility of achieving clinical benefits by inducing oral tolerance highlights the importance of characterizing SSc T-cell antigens. It is hoped that the identification of some of the key players in the induction and maintenance of the SSc fibroblast phenotype may yield new disease-targeted treatment regimens for patients with SSc. © 2008 Elsevier Inc. All rights reserved. [ABSTRACT FROM AUTHOR]

OBJECTIVE: A procollagen alpha2(I) messenger RNA (mRNA) variant, with a 115-bp band and an expected band of 180 bp, was found to be increased during early, acute scleroderma-like disease in UCD-200 chickens. The present study investigated the influence of cytokines on the expression of these 2 proalpha2(I) mRNA variants. METHODS: Embryonic fibroblasts of UCD-200 chickens (UCD-200-CEF) and normal white leghorns (NWL-CEF) were grown in 3-dimensional collagen gels. Procollagen mRNA expression was analyzed by RNase protection assay, and proliferation was determined by (3)H-thymidine incorporation. Transforming growth factor beta1 (TGFbeta1) and TGFbeta2 were measured in culture supernatants by enzyme-linked immunosorbent assay. RESULTS: Compared with NWL-CEF, UCD-200-CEF expressed 7.2 times more of the smaller profibrotic proalpha2(I) mRNA variant. TGFbeta1 stimulated the proliferation of UCD-200-CEF, but not NWL-CEF. The 115 bp:180 bp ratio was increased by TGFbeta1 in both NWL-CEF and UCD-CEF. TGFbeta2 and TGFbeta3 reduced the expression of the profibrotic proalpha2(I) mRNA in UCD-200-CEF to the same levels observed in healthy control NWL-CEF. In culture supernatants, NWL-CEF produced 4.1 times more TGFbeta2 than that produced by UCD-CEF. Inhibition of endogenous TGFbeta2 in NWL-CEF resulted in the same 115 bp:180 bp ratio as seen in untreated UCD-CEF. CONCLUSION: TGFbeta2 reduces the expression of a profibrotic proalpha2(I) mRNA variant in UCD-200-CEF. The constitutive overproduction of this proalpha2(I) mRNA variant and the diminished synthesis of TGFbeta2 in untreated UCD-200-CEF suggest that TGFbeta2 can act as an antifibrotic cytokine and might be a key player during fibrosis onset. These results shed light on the contradictory observations regarding the role of TGFbeta2 in human systemic sclerosis. [ABSTRACT FROM AUTHOR]

Chickens of the Obese strain (OS) develop a spontaneous, hereditary autoimmune thyroiditis during the first weeks of life which parallels human Hashimoto's thyroiditis in all clinical, histopathological and serological aspects. This review summarizes the results from investigations on this strain with special emphasis on the pathogenic effector mechanisms leading to the autoimmune destruction of the thyroid gland. The fact that this model disease arises in an avian species is particularly advantageous because of the clear-cut anatomical and functional division of the immune system. Data are discussed which suggest the following pathogenesis of spontaneous autoimmune thyroiditis: B cells and their products, i.e. thyroglobulin autoantibodies, play a decisive role in the initial phases of the disease, such antibodies are first vertically transferred from the mother hen via the egg yolk into the embryo and newly hatched chick, the immune system of which then takes over their production. T-helper cells are required for the formation of the thyroglobulin autoantibodies. These antibodies can either be complement-fixing or mediate destruction of the target cells via antibody-dependent cellular cytotoxicity (ADCC). B cells themselves also destroy thyroid epithelial cells directly in ADCC-like fashion. Cytotoxic T cells seem to play a minor role in the beginning, but add to the destruction of the thyroid gland later. The underlying defect appears to be a deficient intrathymic maturation of suppressor cells leading to a lack of their emigration to the periphery. The development of the disease is under multigenic control, involving at least three loci. Genes associated with the B locus [the major histocompatibility complex (MHC) of the chicken] and a non-B locus seem to be responsible for the immunological hyperreactivity of the OS towards autologous (thyroid and non-thyroid) and exogenous antigens. The third locus is considered to determine a primary thyroid defect thus predisposing this organ as a prime target for the manifestation of autoimmune disease in the OS. [ABSTRACT FROM AUTHOR]

Autoantibodies in the sera of patients with Goodpasture's syndrome showed a strong reaction in indirect immunofluorescence tests on unfixed, frozen sections of a mouse tumour (EHS sarcoma), previously shown to produce extracellular basement membrane. Anti-basement membrane antibodies from patients with bullous pemphigoid failed to react with the mouse tumour, but showed a distinct reaction with cylindroma tissue. Absorption of Goodpasture sera with tumour homogenate completely abolished their reaction on sections of human and murine kidney. Basement membrane (type IV) collagen and a high molecular weight, non-collagenous glycoprotein were isolated from the tumour matrix and studied in absorption experiments and radioimmunoassays. Little or no reaction was observed with Goodpasture patients' sera indicating that neither of these two proteins is the major antigen involved in the disease. Antigenic material reacting with Goodpasture sera was extracted from the tumour in neutral salt solutions, suggesting that it is a non-collagenous protein. [ABSTRACT FROM AUTHOR]

The sensitivity of rat pregnancy to luteinizing hormone (LH) depletion on days 7-12 (day 1 = day of insemination) was investigated by intraperitoneal administration of a single injection of various doses of an anti-bovine LH rabbit serum on the day in question. Day 11 was found to be the most susceptible time for this kind of intervention. The fate of the anti-LH antibodies in the recipients was followed in the scrum and in various organs of the treated animals. Serological analysis revealed persistence of free antibodies to LH in the serum as late as 48 hr after injection. Immunofluorescence studies showed immune complex deposition in the kidney glomerula. [ABSTRACT FROM AUTHOR]

The Obese strain (OS) of chickens spontaneously develops autoimmune thyroiditis several weeks after hatching, characterized by severe lymphoid infiltration and circulating thyroglobulin antibody. Sundick & Wick (1974) found that the thyroid glands of OS embryos and newly hatched chicks actually incorporated more 131I than normal controls when the parents of both groups were fed a Protamone-supplemented diet. Since this material-an iodinated casein containing thyroactive substances-drastically reduced thyroidal uptake of 131I several experiments were designed to compare OS and normal chicks free from these effects. In the first experiment the dietary supplementation of OS and normal hens were changed from Protanione to pure thyroxine and triiodothyronine. Their eggs were collected daily and incubated. The hatched chicks were tested for 20-hr 131I uptake and it was determined that 11-18 days after the food switch, the inhibition of uptake by Protamone was reversed, and the newly hatched OS chicks still had a significantly increased 20-hr 131I uptake when compared to the normal controls. Comparison of the offspring of a special hock of OS hens that lays without hormonal supplementation, with the parental Cornell C strain from which the OS is derived, similarly revealed a higher 20-hr 131I uptake by the OS (P < 0.005). The increased thyroidal uptake of OS was apparent as early as 4 hr after 131I administration and seemed to be independent of slight variations in the amount of 127I available to the chicks, and also seemed to be independent of maternally derived thyro- globulin antibody vertically transferred into OS chicks. These results suggest that an abnormality of the OS thyroid gland might be a prerequisite for the spontaneously occurring autoimmune thyroiditis in this strain. [ABSTRACT FROM AUTHOR]

Thyroid glands of Obese strain (OS) chickens with spontaneous hereditary autoimmune thyroiditis were studied by direct immunofluorescence (DIF) with an anti-chicken immunoglobuiin-FITC conjugate for local immunoglobulin (Ig) production in plasma cells and germinal centres. Many plasma cells and most of the germinal centres showed positive staining in DIF. The lg property of this stained material was verified by DIF blocking and indirect immunofluorescence (IIF) tests with specific unlabelled anti-chicken Ig sera. In a chronological DIF study of thyroid glands from OS chickens aged 1-18 weeks, Ig-producing plasma cells could be already detected in the 1st week of life. DIF tests with TRITC-labelled chicken thyroglobulin revealed positive staining of plasma cells with preferential localization in ciose proximity to, or even between, follicular epithelial cells, suggesting the anti-thyroglobulin autoantibody nature of at least some of the locally produced Ig. Positive results in DIF and IIF tests performed on infiltrated thyroid glands of OS chickens immunized with bovine serum albumin indicated the capacity of many infiltrating lymphoid cells within the thyroid to respond to exogenous antigens too. [ABSTRACT FROM AUTHOR]

Studies the delineation of different antigenic surface determinants on the surface of adult peripheral T cells by means of a specific horse anti-human T-cell serum. Evidence showing the presence of a close steric relationship between E receptors and T antigens; Evidence showing that the E receptor and T antigens are separately mobile within the T-cell membrane.

Appropriately absorbed turkey antisera to antigenic surface determinants of chicken bursa (ABS) or thymus cells (ATS) were assessed for their selective immunosuppresive activity in vitro and in vivo. The intraperitoneal injection of ABS or ATS in 2-3-week-old normal white Leghorn chickens entailed a significant depletion of B or T cells respectively from spleen and peripheral blood, while bursa and thymus themselves remained unaffected. The potential of this 'peripheral serological bursectomy and thymectomy' paralleled that found after the conventional surgical procedures with subsequent sublethal irradiation. The mean survival time in skin allografts from donors of genotype B4B4 onto B8B8 recipients was significantly prolonged by treatment with ATS (29 ± 12 days) as compared to untreated (14 ± 2 days), normal turkey serum (12 ± 3 days) or ABS-injected (13 ± 2 days) groups. This selective suppression of a T cell-dependent immune reaction by ATS was also confirmed in vitro by its inhibitory action on the graft-versus-host reactivity of adult peripheral blood lymphocytes in the chorioallantoic membrane assay, where normal turkey serum and ABS were again ineffective. Thus, ABS or ATS produced in avian species may serve not only to delineate B and T cells in vitro, but can also be used for selective manipulation of immune reactions of the chicken in vivo. [ABSTRACT FROM AUTHOR]

The main histological feature of cylindroma is the deposition of sheaths of a ‘hyalinized’ material contiguous to the tumour cell clusters. Although ultrastructural studies of this material have revealed a basement membrane-like structure, its exact nature has remained unclear. Using immuno-staining with affinity-purified antibodies directed against distinct basement membrane components, we have shown that type IV collagen and laminin are major constituents of this zone. In addition, cell culture studies indicated that both proteins are synthesized by the tumour cells. The immunohistological data make it clear that the tumour matrix between the tumour cell islands is composed not only of basement membrane components, but also is composed of other connective tissue constituents, i.e. type I and III collagen and fibronectin. [ABSTRACT FROM AUTHOR]

Basement membrane (type IV) collagens were extracted from a mouse tumour with acetic acid and from human placenta after limited enzymatic digestion. Antisera were produced against both collagens in rabbits and guinea-pigs and examined by various assays. These antisera were found to be specific for basement membrane collagen and showed little or no cross-reactions with the interstitial collagens, types I, II and III or with human placenta collagen consisting of αA and αB chains. Varying degrees of cross-reaction were observed between antisera to human and mouse type IV collagen. Immunochemical analyses demonstrated the presence of three distinct determinants in the tumour type IV collagen. Rabbit antisera against this antigen reacted with either collagenase-resistant segments or with a collagenous, disulphide-bonded segment (P3). Guinea-pig antisera recognized primarily antigenic determinants in the P3 segment. Antisera to placenta type IV collagen reacted with another collagenous, pepsin fragment (P1) which lacks disulphide bonds. These antisera showed complete cross-reaction with collagenous αI(IV) chains prepared from pepsin-digests of human placenta and bovine lens capsule. [ABSTRACT FROM AUTHOR]