Anaphylaxis after first exposure to ceftriaxone.

UNLABELLED: Life-threatening anaphylaxis developed in a 5-y-old boy with septic shock within minutes of receiving his first intravenous injection of ceftriaxone. Hypersensivity could not be demonstrated by skin testing and ceftriaxone-specific IgE. However, an in vivo, controlled, intravenous challenge was clearly positive. CONCLUSION: Clinicians should be aware of the possibility of anaphylaxis occurring with the first dose of ceftriaxone, especially since such a reaction could go unnoticed in patients with life-threatening infections and unstable vital signs.

Splenic abscess caused by Peptostreptococcus species, diagnosed with the aid of abdominal computerized tomography and treated with percutaneous drainage and antibiotics: a case report.

We describe herein a 63-year-old patient with a splenic abscess due to Peptostreptococcus spp., diagnosed with the aid of abdominal computerised tomography and treated with ultra-sound guided percutaneous drainage and antibiotics. The bacteriological characteristics of splenic abscesses are discussed.

Severe mycobacterial and Salmonella infections in interleukin-12 receptor-deficient patients.

Interleukin-12 (IL-12) is a cytokine that promotes cell-mediated immunity to intracellular pathogens by inducing type 1 helper T cell (TH1) responses and interferon-gamma (IFN-gamma) production. IL-12 binds to high-affinity beta1/beta2 heterodimeric IL-12 receptor (IL-12R) complexes on T cell and natural killer cells. Three unrelated individuals with severe, idiopathic mycobacterial and Salmonella infections were found to lack IL-12Rbeta1 chain expression. Their cells were deficient in IL-12R signaling and IFN-gamma production, and their remaining T cell responses were independent of endogenous IL-12. IL-12Rbeta1 sequence analysis revealed genetic mutations that resulted in premature stop codons in the extracellular domain. The lack of IL-12Rbeta1 expression results in a human immunodeficiency and shows the essential role of IL-12 in resistance to infections due to intracellular bacteria.

Defects in monocyte polarization and dendritic cell clustering in patients with Graves' disease. A putative role for a non-specific immunoregulatory factor related to retroviral p15E.

A depressed chemotactic responsiveness of monocytes and a depressed cluster capability of dendritic cells have been found in diseases such as chronic purulent infections of the respiratory tract and in various types of malignancies. These impairments in monocyte and dendritic cell function could be ascribed to the action of a low molecular weight factor (LMWF; less than 25 kDa) circulating in the serum of the patients. The factor, which seems to be a non-specific immunoregulatory factor, shares a structural homology with p15E, the capsular protein of murine and feline leukaemogenic retroviruses. In order to study the chemotactic responsiveness of monocytes and the cluster capability of dendritic cells of Graves' patients, monocytes were isolated from the peripheral blood and dendritic cells were prepared from these peripheral blood monocytes by exposure to metrizamide. Monocytes were studied for their chemotactic responsiveness measuring their capability to polarize (morphological changes determined by light microscopy) after stimulation with the chemoattractant fMLP. Dendritic cells were studied for their capability to form clusters with allogeneic lymphocytes. A defective fMLP-induced monocyte polarization was found (16 vs 37% in healthy controls), whereas the dendritic cells showed a defective clustering (60 clusters vs 151 clusters in healthy controls). The effect of fractions of less than 25 kDa prepared from the serum of Graves' patients on healthy donor monocytes and dendritic cells was studied to test the presence of p15E-like factors. The serum fractions had a significant inhibitory effect on monocyte polarization and dendritic cell clustering.(ABSTRACT TRUNCATED AT 250 WORDS)

Dendritic cells and class II MHC expression on thyrocytes during the autoimmune thyroid disease of the BB rat.

The BB rat is a well-established model for spontaneous thyroid autoimmune disease. Since antigen presentation in thyroid autoimmunity is still a matter of debate, we studied the presence of antigen-presenting dendritic cells in the thyroid of the BB/O rat during the development of the disease in relation to the presence of other leucocytes and the aberrant expression of class II MHC determinants by thyrocytes. Thyroid glands, as well as thyroid-draining lymph nodes, were investigated in enzyme histochemistry and immune histochemistry. The appearance of anti-colloid antibodies in the circulation at 6 weeks of age was accompanied by an increase in the weight of the thyroid-draining cervical lymph nodes, which contained many anti-thyroglobulin-producing plasma cells. The only noteworthy event in the thyroid gland in this early stage of the disease was an increase in the number of dendritic cells. T cells, B cells, and plasma cells were virtually absent from the thyroid, and thyrocytes were invariably negative for class II MHC determinants. Only after 18 weeks of age, when large accumulations of dendritic cells, B lymphocytes, and T lymphocytes were seen in 40% of the BB thyroids, could some class II MHC positive thyroicytes be observed. At this stage the thyroid also contained some anti-thyoglobulin-producing plasma cells. Our observations suggest that dendritic cells play a role in antigen presentation in the early stages of the thyroid autoimmune response.

A diminished adherence of blood lymphocytes of patients with thyroid autoimmune disease to high endothelial venules in the thyroid and the thyroid-draining lymph nodes.

The function of high endothelial venules (HEVs), present in the T-cell area of lymphoid tissue is to attract lymphocytes to secondary lymphoid organs ("homing"). In Graves' disease, sporadic goitre and lymphocytic thyroiditis HEVs develop in the thyroid. To study the "homing" of peripheral blood lymphocytes (PBL) of healthy individuals and thyroid patients to the thyroid area we studied the adherence of PBL of such individuals to HEVs present in Hashimoto's goitres and to HEVs in thyroid draining lymph nodes. A modification of the in vitro "homing assay" described by Stamper and Woodruff (J Exp Med 144: 823) was used. The number of PBL of patients with Graves' disease which adhered to thyroidal and thyroid-draining lymphnode HEVs was significantly (p less than or equal to 0.001, Wilcoxon test) less than that of healthy control PBL's; in the case of thyroid HEVs 12 (mean, sd 8, n = 18) patient lymphocytes adhered to 35 HEVs vs 19 (mean, sd 7, n = 16) healthy control lymphocytes; in the case of thyroid lymphnode HEVs 20 (mean, sd 12, n = 15) patient lymphocytes adhered vs 35 (mean, sd 9, n = 9) healthy control lymphocytes. PBL of a few sporadic goitre (n = 5) and atrophic lymphocytic thyroiditis (n = 2) patients also showed a diminished adherence to thyroidal HEVs. We also studied the homing capability of lymphocyte suspensions isolated from the thyroid glands of three Graves' disease patients; these infiltrated cells showed a normal adherence pattern to thyroidal HEVs. We favour the idea that the data should be explained by a redistribution of lymphocytes possessing "thyroid-specific-homing-receptors" from the circulation to the thyroid area in patients with thyroid autoimmune disease.

Dendritic cells and scavenger macrophages in pancreatic islets of prediabetic BB rats.

Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease whose notorious pathologic feature is insulitis accompanied by destruction of beta-cells. In this morphological study, we examined the pancreatic events during the onset of diabetes in spontaneously diabetic BB/Organon rats. Dendritic cells were the first cells to accumulate around the islets, followed by lymphocytes. Scavenger macrophages and MHC class II-positive beta-cells were only seen late in the disease. These observations suggest a role for antigen-presenting dendritic cells in the onset of the beta-cell-specific autoimmune reaction and emphasize the necessity to distinguish between the several monocyte-macrophage subtypes in studies on the pathogenesis of IDDM.

Accessory cells with a morphology and marker pattern of dendritic cells can be obtained from elutriator-purified blood monocyte fractions. An enhancing effect of metrizamide in this differentiation.

Human monocytic cell fractions obtained by counterflow elutriation centrifugation (with regard to specific monocyte/macrophage characteristics: 82-88% were positive for nonspecific esterase; 86-94% for CD14) were cultured (overnight, 37 degrees C) under nonadhering conditions (polypropylene tubes). Thirty to 40% of the cells were found to differentiate into large, monocytoid cells with a dendritic morphology. These cells expressed a marker of active dendritic cells RFD1 in 76-89% and were also positive for class II MHC antigens as identified by OKIa (95-97%). An exposure of the blood monocytic cells to metrizamide (30 min, 14.5%) prior to the overnight culture enhanced this differentiation, and 47-58% of cells with a dendritic morphology were found (of which 80-87% RFD1 positive, and 95-97% Class II MHC positive). The cultured cell populations containing the cells with the morphology and marker pattern typifying dendritic cells, appeared functionally more active as accessory populations when compared to freshly isolated blood monocytic cell fractions; the cultured cells had an enhanced stimulator capability in MLR, and cluster formation with lymphocytes was more prominent. At the same time, the cultured cell population showed a decreased bactericidal activity when compared to the freshly isolated monocytic populations, and in addition, all the cultured monocytoid cells had lost non-specific-esterase activity, while only approximately 10% of cells were still positive for the CD14 marker. When U937 cells were exposed to metrizamide (14.5% concentration, 30 min) and cultured under nonadhering conditions for 36 hours, similar changes were observed (30-45% became dendritic, 20% RFD1 positive).(ABSTRACT TRUNCATED AT 250 WORDS)

Intrathyroidal dendritic cells, epitheloid cells, and giant cells in iodine deficient goiter.

Immunohistochemistry and immunofluorescence were performed on thyroid sections of 44 consecutive patients undergoing thyroid surgery for goiter due to iodine deficiency. Sections were compared with specimens from ten individuals without goiters from the same endemic area, with specimens from ten sporadic nontoxic goiter patients, and with specimens from an area with sufficient iodine supply from nine healthy subjects. Cells were characterized using monoclonal antibodies to the CR3 receptor (CD11b) and the p150/95 antigen (CD11c) present on macrophages, to HLA-DR, to antigen presenting cells (RFD1), to T helper (CD4) and to T suppressor/cytotoxic cells (CD8), and with a polyclonal antibody to human cytokeratin. In iodine deficient goiters, focal aggregates were found of RFD1-positive dendritic cells. Furthermore, RFD1-positive epitheloid cells were seen. In 27% of cases, these epitheloid cells completely filled the thyroid follicles. Within the epitheloid cell clusters, multinucleated giant cells could be detected that carried the macrophage markers. Dendritic cells, epitheloid cells, and giant cells were strongly HLA-DR positive. In nongoitrous thyroids from the endemic area such aggregates could also be seen but they were more sparse and were RFD1 negative. Giant cells were absent there. In normal thyroids with sufficient iodine supply, only a few isolated dendritic cells were seen. All except RFD1, which was negative, showed the same marker pattern. In sporadic nontoxic goiters from an area with sufficient iodine supply, dendritic cells occurred in much higher numbers than in the normal thyroids from that area, and they were RFD1 positive. They never aggregated as in iodine deficiency, and giant cells were not observed. These observations on iodine deficient goiter strongly suggest involvement of active antigen-presenting cells in this disorder. However, the immunohistologic difference between this disease and sporadic goiter suggests different underlying mechanisms.

High endothelial venules present in lymphoid cell accumulations in thyroids affected by autoimmune disease: a study in men and BB rats of functional activity and development.

High endothelial venules (HEVs) derive their name from the cuboidal high walled shape of the endothelial cells and are found in T-cell areas of a wide variety of lymphoid tissues. The function of HEVs is to attract lymphocytes to lymphoid tissues, and they are thus of importance in lymphocyte recirculation. We investigated the immunohistochemical presence and localization of HEVs in thyroid tissue obtained at surgery from 13 patients with Graves' disease and 3 patients with Hashimoto's disease using the monoclonal antibody HECA 452, which reacts with an epitope on human HEVs. HEVs were found in large confined lymphocytic accumulations in 7 of the 13 Graves' disease glands and all of the Hashimoto's disease glands. These lymphocytic accumulations showed a high grade of architecture and were composed of a central B-cell follicle and a T-cell area in which the HEVs were present. The HEV-containing T-cell area formed a corona around the B-cell follicle. Plasma cells were found at the periphery of the intrathyroidally developed lymphoid tissue. In BB rats, an animal model for spontaneous autoimmune thyroid disease, the development of such HEVs containing intrathyroidal lymphoid tissue was a rather late phenomenon in the autoimmune process occurring after the appearance of anticolloid antibodies in the circulation and after initial immune activity of the thyroid draining lymph nodes. The actual development of the intrathyroidal lymphoid tissue was initiated by accumulation of lymphocytes around dendritic cells forming small cellular clusters. These small clusters later developed into larger formation in which HEVs were detectable. The adherence of B- and T-lymphocytes to human intrathyroidal HEVs was additionally studied using an in vitro adherence assay. B-Lymphocytes preferentially adhered to thyroidal HEVs. This adherence pattern is similar to that of HEVs in mucosa-associated lymphoid tissue (tonsils and Peyer's patches). We conclude that lymphoid tissue with a lymphocyte recirculation pattern similar to that of mucosa-associated lymphoid tissue can be found in thyroid glands involved in a process of autoimmune reactivity; the BB rat study suggests that the development of such tissue occurs during the chronic phases of the process.

Intrathyroidal dendritic cells.

The presence, marker pattern, and ultrastructure of antigen-presenting dendritic cells were studied in normal thyroid glands from 9 subjects (6 obtained at surgery; 3 at autopsy) and in the thyroid glands form 13 patients with Graves' hyperthyroidism, 10 patients with simple nontoxic goiter, and 1 patient with Hashimoto's disease (all obtained at surgery). The immunohistochemical characterization of the cells was carried out using the monoclonal antibodies OKIa (class II MHC determinants), RFD1 and L25. These latter monoclonal antibodies react strongly with active dendritic cells in T-cell areas of secondary lymphoid organs (the interdigitating cells in lymph nodes and spleen). Antigen-presenting dendritic cells were defined as cells with an eccentric reniform nucleus, long cytoplasmic protrusions, and strong membrane-bound class II MHC positivity combined with little or no cytoplasmic acid phosphatase activity. According to these criteria normal human thyroid tissue contained a few dendritic cells; they were localized outside the thyroid follicles. These dendritic cells in normal thyroid tissue lacked the marker molecules identified by the monoclonal antibodies RFD1 and L25. In fact, the majority of the dendritic cells were strongly positive for the C3bi receptor (identified by the monoclonal antibody FK 24), which indicates a more monocyte/macrophage character of the cell. In Hashimoto's goiter, Graves' disease, and sporadic nontoxic goiter (which we consider an autoimmune thyroid disease) the numbers of dendritic cells were higher compared to those in the normal gland, and these dendritic cells were clearly positive for RFD1 and L25. The cells were often seen in contact with a few intrathyroidal lymphocytes, forming small lymphoid cell clusters. They were also found in the T-cell zones of larger well organized intrathyroidal lymphoid structures (focal thyroiditis). On ultrastructural examination the dendritic cells in Graves' glands, Hashimoto's goiter, and sporadic nontoxic goiter were similar to the interdigitating cells present in secondary lymphoid organs. The data suggest active involvement of dendritic cells in the immune process in the thyroids of patients with autoimmune thyroid disease.

Dendritic cells in autoimmune thyroid disease.

Dendritic cells form a morphologically distinct class of cells characterized by shape, reniform nucleus, absent to weak acid-phosphatase activity and strong Class II MHC determinant positivity. Functionally they are the most efficient cells in antigen presentation to T-lymphocytes which indicates their role in the initiation of an immune response. Using immunehistochemical techniques we studied the presence of dendritic cells in normal Wistar rat and human thyroids, in thyroids of BBW rats developing thyroid autoimmunity and in Graves' goitres. Dendritic cells could be identified in all thyroids studied and were positioned underneath the thyrocytes in between the follicles. Skin dendritic cells travel via lymphatics to draining lymph nodes, thus forming an antigen presenting cell system. It is likely that a similar cell system exists on the level of the thyroid for dendritic cells have also been detected in thyroid draining lymph nodes. In normal thyroid tissue of both human and rat dendritic cells were relatively scarce. During the initial phases of the thyroid autoimmune response in the BBW rat (before the appearance of Tg-antibodies in the circulation) numbers of thyroid dendritic cells increased. Intrathyroidal T-helper cells, B-cells or plasma cells could not be found. The thyroid draining lymph node contained large numbers of plasma cells. During the later stages of the thyroid autoimmune response in the BB/W rat (after the appearance of Tg-antibodies in the circulation) and in Graves' goitres dendritic cells were not only present in high number, but 20-30% were seen in contact with now-present intrathyroidal T-helper lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)