A 17-year-old with rash, fever, myalgias, and nephritis

Patients on hemodialysis are at increased risk for developing active tuberculosis (TB) after primary infection. Although this increased risk is well documented, the prevalence of TB infection, as indicated by a positive tuberculin skin test (TST), is not well described. End-stage renal disease is also known to be a risk factor for skin test anergy, but the rate of anergy in hemodialysis patients is unclear. We sought to identify rates of anergy and TST positivity in patients at four hemodialysis units in St Louis, Missouri, from June 1996 through August 1996. Data obtained from patients and medical records included age, years on hemodialysis, medical history, and basic laboratory data. Patients without a history of TB or a positive TST had a TST with Tubersol, as well as candida and tetanus controls, placed by the Mantoux method. Tests were read 48 hours later. Of the patients enrolled at these units, 307 of 331 (93%) were evaluated. Patients had a mean age of 58 years (range, 19 to 91 years) and had been on hemodialysis for a mean of 3.7 years (range, 1 week to 18.7 years). Blacks made up 81% of the population. A history of a positive TST was obtained from 24 patients (8%), and an additional seven (2%) had a history of active TB. Of the 276 patients tested, 93 did not respond to either control antigen, but five of these patients had a positive TST, leaving 88 (32%) anergic. Anergy was related to age, immunosuppressive drug use, and the reagents used, but not to urea reduction ratio. Positive TSTs were found in 17 of 188 of nonanergic patients (9%) (6% of all tested patients). Overall, 48 of 307 patients (16%) had a positive TST or history of TB. TB or a positive TST was associated with liver disease and peptic ulcer disease, but not socioeconomic status. All 17 newly identified TST-positive patients received chest radiographs. No new cases of active TB were found. Only two of 17 of these patients (12%) were started on isoniazid (INH) prophylaxis. We identified high rates of TST positivity and anergy in the hemodialysis patients tested. Hemodialysis patients should receive regular TST screening, and INH prophylaxis needs to be more strongly encouraged. Studies are ongoing to define the rate of TST conversion over time.     

Ki-67 and grading of malignant fibrous histiocytomas

Although generally considered to be of high grade, malignant fibrous histiocytomas (MFH) show a range of histologic appearances and a diverse biologic behavior. More precise grading of this type of sarcoma is desirable. The rate of cell proliferation may reflect clinical behavior. A more sensitive measure of cell proliferation is the expression of the Ki-67 antigen. Frozen sections were prepared from 29 cases of MFH. Sections were immunohistochemically stained for Ki-67, and the results were quantitated by image analysis (CAS 100). The Spearman rank correlation test was used to compare the extent of the Ki-67 staining with the conventional histologic grade, nuclear grade, number of mitoses, extent of necrosis, and overall cellularity. There was a significant correlation between the extent of Ki-67 staining and the nuclear grade (cc = 0.56; P = 0.002) and overall histologic grade (correlation coefficient = 0.58; P = 0.001), but there was no significant, independent correlation between Ki-67 and prognosis.     

Human macrophage maturation and heterogeneity: analysis with a newly generated set of monoclonal antibodies to differentiation antigens

We have analyzed the expression of late differentiation antigens during terminal in vitro maturation of human macrophages (M phi) from blood monocytes (MO) in comparison to their distribution among mature M phi residing in various tissue sites. By immunizing mice with M phi derived from blood MO by culture on hydrophobic Teflon foils, monoclonal antibodies (mAbs) were developed (MAX.1, MAX.2, MAX.3, MAX.11) that reacted with lineage-restricted differentiation antigens. These antigens were expressed exclusively on M phi or were markedly increased after in vitro differentiation. The only overlap to another hemopoietic cell lineage was observed with MAX.3, which is shared by platelets and megakaryocytes. In the course of M phi maturation in vitro, the MAX.1 and MAX.3 antigens are detected within the cytoplasm two days before they appear on the cell surface. In contrast, the MAX.11 antigen is expressed simultaneously in the cytoplasm and at the cell surface, is found in varying degrees on a minor portion of blood MO and U937 cells, and is expressed rapidly at high density during early M phi differentiation in vitro. Among conventional mAbs that do not react with MO we found those against the transferrin (TF)-receptor, the BA-2, and the PCA1 antigen to label M phi. M phi matured in vivo and isolated from body fluids were positive with some but not all MAX mAbs. Distinctive patterns were observed with pulmonary M phi, exudate M phi from pleural and peritoneal effusions, synovial fluids, and early lactation milk. M phi from the alveolar space, for example, constantly expressed the MAX.2 antigen but not the MAX.3 antigen. Pleural effusion M phi, however, did not react with the MAX.1 mAb, but in most cases, it did react with the MAX.3 mAb. The detection of novel differentiation antigens, all expressed on monocyte-derived M phi but differently expressed on site-specific M phi in situ, underlines the remarkable heterogeneity among human M phi. The expression of these antigens is flexible because those MAX antigens that were not expressed in situ could be induced if cells from distinct tissue sites were cultured in vitro for several days. MAX mAbs may be of potential value to study both the sequential stages of maturation within the M phi lineage as well as differential developments induced by various culture conditions in parallel to environmental factors in vivo.     

内皮下脂蛋白滞留——动脉粥样硬化的始动过程

以动脉粥样硬化为基础的心血管疾病是人类健康面临的严重挑战.人们对动脉粥样硬化发生、发展进行漫长和不懈的探索.至今,其机制与过程仍不十分清楚.