Unusual immunocytochemical and ultrastructural features of synovial fluid cells in multicentric reticulohistiocytosis. A case report

We present the first report in which cells in synovial fluid from a patient with multicentric reticulohistiocytosis (MRH) were studied by immunocytochemistry for correlation with routine light and electron microscopy. MRH cells stained predominantly for lymphocyte-related surface antigens and not for the monocyte marker LEU M3 (CD14). These findings suggest a lymphocytic origin of MRH cells and not a histiocytic origin, as previously suggested. In addition, large numbers of membrane-bound, electron-dense, secretory-type granules were found ultrastructurally in the cytoplasm of these cells.     

Dissecting the order of bacteriophage T4 DNA polymerase holoenzyme assembly

Most biological organisms rely upon a DNA polymerase holoenzyme for processive DNA replication. The bacteriophage T4 DNA polymerase holoenzyme is composed of the polymerase enzyme and a clamp protein (the 45 protein), which functions as a processivity factor by strengthening the interaction between DNA and the holoenzyme. The 45 protein must be loaded onto DNA by a clamp loader ATPase complex (the 44/62 complex). In this paper, the order of events leading to holoenzyme formation is investigated using a combination of rapid-quench and stopped-flow fluorescence spectroscopy kinetic methods. A rapid-quench strand displacement assay in which the order of holoenzyme component addition is varied provided data indicating that the rate-limiting step in holoenzyme assembly is associated with the clamp loading process. Pre-steady-state analysis of the clamp loader ATPase activity demonstrated that the four bound ATP molecules are hydrolyzed stepwise during the clamp loading process in groups of two. Clamp loading was examined with stopped-flow fluorescence spectroscopy from the perspective of the clamp itself, using a site-specific, fluorescently labeled 45 protein. A mechanism for T4 DNA polymerase holoenzyme assembly is proposed in which the 45 protein interacts with the 44/62 complex leading to the hydrolysis of 2 equiv of ATP, and upon contacting DNA, the remaining two ATP molecules bound to the 44/62 complex are hydrolyzed. Once all four ATP molecules are hydrolyzed, the 45 protein is poised on DNA for association with the polymerase to form the holoenzyme.     

Effects of Ca2+ deregulation on mitochondrial membrane potential and cell viability in nucleated cells following lytic complement attack

We have previously shown [Papadimitriou JC. Ramm LE. Drachenberg CB. Trump BF. Shin ML. (1991) J. Immunol., 147, 212-217] that formation of lytic C5b-9 channels on Ehrlich ascites tumor cells induced rapid depletion of adenine nucleotides associated with prelytic leakage preceding cell death. Extracellular Ca2+ concentration ([Ca2+]e) reduction by chelation markedly delayed the onset of cell death, although the adenine nucleotide leakage was enhanced. In the present study, we examined the temporal relationships between ionized cytosolic Ca2+ ([Ca2+]i), mitochondrial membrane potential (delta psi m) and cell death in individual cells by digital imaging fluorescence microscopy (DIFM), during the earliest phase of C5b-9 attack. The results showed an immediate, > 20-fold rise in [Ca2+]i, rapidly followed by dissipation of delta psi m and subsequent acute cell death. These events were markedly delayed by chelation of Ca2+e, but not by nominally Ca2+ free medium. Differing from previous reports indicating propidium iodide labeling of viable cells bearing C5b-9 channels, with DIFM we observed nuclear fluorescence with that marker only in association with cell death. These findings indicate that Ca2+ influx through lytic C5b-9 channels is responsible for the massive increase in [Ca2+]i, as well as for the rapid loss of delta psi m, followed by acute cell death. When this [Ca2+]i increase is prevented, the cell death is probably related to metabolic depletion.     

Diagnosis and therapy of chronic polyarthritis

Rheumatoid arthritis (RA) is the most frequent inflammatory joint disease, and it affects about 1% of the population. The onset of arthritis is rarely acute; it is subacute and usually progresses slowly. The clinical picture of RA is variable: mild to very aggressive and destructive courses, sometimes accompanied by organ involvement, leading to severe functional impairment and early disability can be observed. RA is diagnosed according to the ACR criteria published in 1958 and modified in 1988. The appearance of a palpable joint swelling or effusion is obligatory for the clinical diagnosis of arthritis. In RA, typically involvement of the joint of the hands and feet can be seen. Laboratory parameters play an important role as both diagnostic and prognostic tools. Besides clinical features and laboratory parameters, imaging techniques provide another cornerstone in the diagnosis of RA. Until now plain X-rays, which primarily visualize osseous changes, are the most important technique in daily practice, whereas magnetic resonance imaging and ultrasound may provide information about soft tissue changes in an earlier stage of disease. The main differential diagnoses of RA to be considered are the seronegative spondylarthropathies (psoriatic arthritis, arthritides accompanying inflammatory bowel diseases, Reiter's syndrome, and spondylitis ankylosans with peripheral arthritis), Parvovirus-induced arthritis, crystal-induced arthritides and septic arthritis. Early diagnosis and therapeutic intervention seem to be of great prognostic importance. In several independently performed investigations a higher mortality was found in RA patients than in the normal population. Drug therapy of RA consists of nonsteroidal antirheumatic drugs (NSAIDs), corticosteroids and disease-modifying drugs (DMARDs). When the functional and radiological parameters were assessed, the DMARDs were found to have a disease modifying and in rare cases a remission-inducing property. Moreover, tolerance these to drugs is limited. Newer therapeutic trials have employed substances like Tenidap, Leflunomid, bacterial extracts, antibiotics and biological subcomes (e.g., monoclonal antibodies against cytokines, fusion proteins for soluble cytokinereceptors). Some promising results of these investigations need confirmation in larger patient populations, but some new perspectives for a more efficacious treatment of RA can be expected.     

Toward targets for initiation of chronic dialysis

OBJECTIVES: To better define the targets for initiation of chronic dialysis, we compared the relationship between the normalized protein equivalent of nitrogen appearance (nPNA, g/kg standard weight/day) and weekly urea clearance (Kt) normalized to total body water (V) in predialysis chronic renal failure (CRF) patients and in patients on continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD). We also studied the relationships of other nutritional parameters to weekly Kt/Vurea in CRF patients. DESIGN: This cross-sectional study was a prospective observational design meant to study each patient once. SETTING: The University Hospital and Clinics and Harry S. Truman VA Medical Center, Columbia, Missouri. PATIENTS: Forty-five consecutive predialysis CRF patients were enrolled and the results compared with patients on CAPD and HD. RESULTS: In CRF, the nPNA calculated from urea appearance correlated with the weekly Kt/Vurea (r = 0.57, p < 0.0001) and, using exponential best-fit, nPNA = 1.217 x (1-e-0.769Kt/V). This exponential relationship was similar to that for CAPD and both were different from that in patients on HD. Likewise, nPNAs, calculated from Kjeldahl nitrogen output, and weekly Kt/Vurea were correlated (r = 0.37, p = 0.014) and, using exponential best-fit, nPNA = 1.102(1-e-0.867Kt/V), similar to the relationship in patients on CAPD. Evidence is presented that these relationships are not explained only by mathematical coupling. There was a significant correlation between the weekly Kt/Vurea and 24-hour urinary creatinine excretion. CONCLUSIONS: The findings suggest that in CRF, as in CAPD, a weekly Kt/Vurea less than 2.0 is likely to be associated with a nPNA less than 0.9 g/kg standard weight. In CRF patients, initiation of chronic dialysis should be considered if weekly renal Kt/Vurea falls below 2.0 and a nPNA greater than 0.8 is desired.     

Effects of ligand priming and multiple-dose injection on tissue uptake of 111In-pentetreotide in rats

In patients undergoing somatostatin receptor scintigraphy, treatment with octreotide (Sandostatin) is usually discontinued 24-48 h before and after injection with the radioligand 111In-pentetreotide ([111In-DTPA(O)]octreotide) (Octreoscan) because octreotide competes with radioligand for the same receptors. However, D?rr et al. and Soresi et al. reported improved visualization of carcinoid and small cell lung cancer lesions, respectively, during continued octreotide treatment. We found that intravenous administration of unlabeled octreotide to rats inhibited the binding of an optimal dose (0.5 microg) of 111In-pentetreotide to somatostatin receptors in pancreas and adrenals in a mass- and time-dependent way. Pretreatment with unlabeled octreotide never increased receptor binding of 111In-pentetreotide. Administration of 100 microg of octreotide decreased receptor-bound radioactivity if given simultaneously with or 10 or 20 min after injection of the radioligand, but had no effect if given 30 min after the radioligand. These findings indicate rapid processing of receptor-bound octreotide and suggest that octreotide treatment of patients undergoing 111In-pentetreotide scintigraphy may be reinitiated as soon as 1 h after radioligand administration.     

Communicating breast cancer on-line: support and empowerment on the Internet

Using participant-observation and discourse analysis, this study explores the communication occurring on the Breast Cancer List, an on-line discussion group which continues to grow in membership and activity. Issues discussed include the evolution of the List, who participates, what topics are discussed. Three major dimensions are identified: exchange of information, social support, and personal empowerment. Social support via computer is compared with face-to-face groups. Empowerment centers on enhanced decision-making and preparation for new illness-related experiences. The influence of gender is considered in terms of communicative style and limitations of access. It is concluded that the List fulfills the functions of a community, with future concerns about information control and the potential to enhance patient-provider understanding.     

Occupational blood exposures in dentistry: a decade in review

This review summarizes data from self-reported and observational studies describing the nature, frequency, and circumstances of occupational blood exposures among US dental workers between 1986 and 1995. These studies suggest that, among US dentists, percutaneous injuries have declined steadily over the 10-year period. Data also suggest that, in 1995, most dental workers (dentists, hygienists assistants, and oral surgeons) experienced approximately three injuries per year. Work practices (eg, using an instrument instead of fingers to retract tissue), safer instrumentation or design (eg, self-sheathing needles, changes in dental-unit design), and continued worker education may reduce occupational blood exposures in dentistry further.