[Phagocytic activity of Gaucher's cells].
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Adult↗
Biomedical subjects
P Fishman
Publications and source records attributed to P Fishman.
Ultrastructural features of the granulocytes in Down's syndrome.
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Basophils↗
[Ultrastructural features of the white blood cells in the leukemias].
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Humans↗
Resistance of muscle to tumor metastases: a role for a3 adenosine receptor agonists.
Tumor metastases are extremely rare in striated muscles. Lately, we have found that muscle cell conditioned medium (MCM) inhibits the proliferation of various tumor cells while maintaining the growth of normal murine bone marrow cells. This dual activity was confirmed in vivo when the MCM was administered orally, i.e., it inhibited the development of tumor growth in mice and prevented the myelotoxic effects of chemotherapy. Adenosine was found to be one of the active components of MCM, inhibiting tumor cell growth while maintaining bone marrow cell proliferation in vitro. Adenosine is known to act as an important regulatory molecule through its binding to specific G-protein-associated A1, A(2a), A(2b) and A3 cell surface receptors. In distinction from MCM, adenosine did not suppress tumor development in mice and was not active as a chemoprotective agent when administered orally or intravenously. Thus, the in vivo activity of MCM could not be attributed to adenosine. In this study, MCM from which adenosine was enzymatically removed still retained its dual activity that was also found to be mediated through the A3 adenosine receptor (A3AR). This result led to the conclusion that natural agonists to A3AR were responsible for the activity of MCM. We further tested synthetic agonist to the A3AR and demonstrated that it possessed the same in vitro and in vivo activity profile as MCM. Taken together, muscle cells, in addition to adenosine, secrete natural agonists to A3AR. These agonists are stable nondegradable molecules and may contribute to the systemic anticancer and chemoprotective activity exerted by MCM. This group of molecules may account for the rarity of tumor metastases in muscle.
Adenosine↗
Chronic care costs in managed care.
This DataWatch presents estimates of the health care costs for all adults who were continuously enrolled in a large staff-model health maintenance organization (HMO) during 1992. More than one-third of these adults were diagnosed with at least one chronic condition in 1992, and costs for this population are at least twice those of the population without chronic conditions. A diagnosis of a chronic condition results in an expected increase in costs of 80 percent-300 percent, depending on age, sex, and chronic condition profile. Previous studies of the costs of chronic illness have focused on the fee-for-service sector. As managed care continues to grow, it is important that economic analyses focus on this market segment.
Adult↗
Phagocytotic activity of monocytes from diabetic patients.
The phagocytotic activity of monocytes from diabetic patients and healthy controls was studied. It was found that the number of phagocytizing cells from diabetic patients was significantly reduced in comparison with that from control individuals. However, the number of bacteria phagocytized per cell was similar in both groups. Plasma from healthy controls added to diabetic monocytes did not cause any significant change in their phagocytotic capacity. Addition of insulin to the plasma of diabetic patients failed to alter the number of phagocytizing diabetic monocytes. Similarly, addition of glucose to control plasma did not affect the number of control monocytes capable of phagocytosis. Protein synthesis was increased during phagocytosis in both control and diabetic cells. The importance of monocytes in the defense mechanism of the organism is discussed.
Adult↗
Preoperative drug dispensing as predictor of surgical site infection.
The system used by the National Nosocomial Infection Surveillance (NNIS) program to measure risk of surgical site infection uses a score of 3 on the American Society of Anesthesiologists (ASA)-physical status scale as a measure of underlying illness. The chronic disease score measures health status as a function of age, sex, and 29 chronic diseases, inferred from dispensing of prescription drugs. We studied the relationship between the chronic disease score and surgical site infection and whether the score can supplement the NNIS risk index. In a retrospective comparison of 191 patients with surgical site infection and 378 uninfected controls, the chronic disease score and ASA score were highly correlated. The chronic disease score improved prediction of infection by the NNIS risk index and augmented the ASA score for risk adjustment.
Case-Control Studies↗
Cost-effectiveness of strategies to enhance mammography use.
OBJECTIVE: To estimate the cost-effectiveness of three strategies to increase breast cancer screening with mammography (reminder postcard, reminder telephone call, and motivational telephone call). DESIGN: Cost accounting for each strategy followed by cost-effectiveness analysis. DATA SOURCE FOR EFFECTIVENESS: Randomized trial of three strategies conducted at Group Health Cooperative of Puget Sound (GHC). TARGET POPULATION: Women 50 to 79 years of age who were enrolled in GHC's breast cancer screening program who did not schedule screening mammography within 2 months after it was recommended by letter. PERSPECTIVE: Health plan. OUTCOME MEASURE: Marginal cost-effectiveness of each additional woman screened. RESULTS OF BASE-CASE ANALYSIS: Because of its high cost (about $26 per call) and intermediate effectiveness, the motivational call was the least cost-effective strategy. If it was assumed that 50% of the women who scheduled mammography after receiving the reminder postcard would have scheduled mammography within 10 months even without it, marginal cost-effectiveness for the postcard among all women was $22 per woman screened versus $92 for the reminder call. Among women with no previous mammography, the marginal cost-effectiveness for the postcard was $70 versus $100 for the reminder call. RESULTS OF SENSITIVITY ANALYSIS: Among women with no previous mammography, the choice between the reminder postcard and the reminder call was sensitive to assumptions about the percentage of women expected to receive mammography in the absence of other promotional strategies. CONCLUSIONS: A simple reminder postcard is the most cost-effective way to increase mammography. Choices about how to promote mammography will ultimately depend on plan values and willingness to invest in promotional strategies that increase participation at higher unit costs.
Aged↗
Functional and ultrastructural studies of Sezary cells.
A patient having clinical findings and typical ultrastructure of the peripheral white blood cells compatible with the diagnosis of Sézary syndrome is described. Studies of the synthesizing capacity of the Sézary cells showed a statistically significant increase in their capacity for protein and RNA synthesis, but no difference with regard to DNA synthesis as compared to normal lymphocytes.
Blood Proteins↗
Clinical and ultrastructural observations in primary acquired sideroblastic anemia.
The clinical and laboratory findings in three patients with primary acquired sideroblastic anemia (PASA) are described. The results demonstrate that what seems to be a well defined entity of the large group of sideroblastic anemias, is in itself a heterogeneous subgroup, with differences capable of detection by more extensive studies. Electron microscopic examination of erythroid cell precursors confirmed previously described features such as deposition of large amounts of iron, mainly in the mitochondria. The precipitated serum proteins revealed an increased content of ferritin molecules only in the patients and not in control individuals, suggesting an increased supply of iron to the erythroid precursors. This finding could serve as an additional mechanism for the accumulation of iron in the erythroid precursors, considering also the defect in heme synthesis and increased permeability of the erythroid membrane for iron, described in this condition.
Aged↗
IB-MECA, an A3 adenosine receptor agonist prevents bone resorption in rats with adjuvant induced arthritis.
OBJECTIVES: The anti-inflammatory effect of adenosine is partially mediated via the A3 adenosine receptor (A3AR), a Gi protein associated cell surface receptor. The highly selective A3AR agonist, IB-MECA was earlier shown to prevent the clinical and pathological manifestations of arthritis in experimental animal models of collagen and adjuvant induced arthritis (AIA). In this study we tested the effect of IB-MECA on the prevention of bone resorption in AIA rats and looked at the molecular mechanism of action. METHODS: Rats with AIA were treated orally twice daily with IB-MECA starting upon onset of disease and the clinical score was evaluated every other day. At study termination the foot, knee and hip region of both vehicle and IB-MECA treated animals were subjected to histomorphometric analysis. Western blot analysis was carried out on paw protein extracts. RESULTS: IB-MECA ameliorated the clinical manifestations of the disease and reduced pannus and fibrosis formation, attenuated cartilage and bone destruction and decreased the number of osteoclasts. In cell protein extracts derived from paw of AIA rats, A3AR was highly expressed in comparison to naïve animals. In paw extracts derived from IB-MECA treated AIA rats, down-regulation of the A3AR protein expression level was noted. PI3K, PKB/Akt, IKK, NF-kappaB, TNF-alpha and RANKL were down-regulated whereas caspase 3 was up-regulated. CONCLUSION: IB-MECA, a small highly bioavailable molecule, induces modulation of proteins which control survival and apoptosis resulting in the amelioration of the inflammatory process and the preservation of bone mass in AIA rats.
Adenosine↗
Kinetics of cortisol, interleukin-2 and interleukin-3-like activity levels following surgical intervention.
Cortisol, interleukin(IL)-2 and IL-3-like activity (IL-3-LA) levels were examined in two groups of patients before and after surgery. One group consisting of 11 patients underwent cholecystectomy; the other comprising 17 patients with malignant diseases of the gastrointestinal tract underwent a removal of the tumor. In both groups there were similar fluctuations in cortisol levels after surgery, i.e. a statistically significant increase at day 2 after operation with a decrease to normal values at day 14. The levels of IL-2 and IL-3-LA production in the two groups followed a different pattern. In patients with cholecystectomy the IL-2 and IL-3-LA levels showed a marked decrease at day 2 with a gradual increase on the following days. In cancer patients IL-2 was at its lowest level before surgery and started to increase gradually till day 14 after surgery. The lowest level of IL-3-LA was at day 2 after surgery and it increased gradually from day 7 to 14. It is suggested that the fluctuations of these two cytokines after surgery are related to the levels of corticosteroids which have been shown to inhibit the production of IL-2 and IL-3-LA in vitro. The observed increase of cortisol level with a concomitant decrease of IL-2 and IL-3-LA after surgery may further explain the immunosuppression observed after operation.
Adult↗
Cytokines, interleukin-3 and autoimmunity.
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Animals↗
Ultrastructural observations in myopathy complicating Cushing's disease.
The ultrastructural findings in a muscle biopsy of a patient with Cushing's disease associated with severe myopathy are described. They included pronounced mitochondrial damage, thickening and deep invaginations of the sarcolemmal basement membrane, and thickening of the basement membrane of the capillaries. In addition, the muscle fibers showed a marked degree of disarray and wide interfibrillar spaces, containing large numbers of vacuoles, which presented degenerated mitochondria. The similarity between these findings and the ultrastructural features of corticosteroid-induced myopathy is discussed.
Cushing Syndrome↗
Superantigens and experimental SLE induced by idiotypic dysregulation.
OBJECTIVE: The effects of the superantigens (SAgs) Staphylococcal Enterotoxin B (SEB), Toxic Shock Syndrome Toxin-1 (TSST-1) and Mycoplasma Arthritidis Mitogen (MAM) were examined on the induction and on the course of experimental SLE-like disease. METHODS: Immunization of BALB/c mice with human anti-DNA mAb (MIV-7) carrying the pathogenic idiotype 16/6 emulsified in complete Freund's adjuvant (CFA), followed by a boost of MIV-7/PBS 3 weeks later, generated an experimental SLE via an idiotypic dysregulation. RESULTS: After immunization with MIV-7/SAg, replacing the MIV-7 boost by SAg, and then injecting SAg 7 weeks after the regular induction of the SLE-like disease, the mice failed to produce anti-hIgM and dsDNA Ab up to 6 months after the induction. The mice immunized with MIV-7/CFA and boosted with the SAg had high titers of anti-hIgM but no detectable anti-dsDNA Ab. In both experimental groups low titers of anti-CL Abs developed in 25/40 (62%) and 30/38 (79%) of the mice respectively, including the control mice immunized with non-pathogenic human IgM/SAg or PBS/SAg. The mice immunized according to the "classical" protocol showed increased titers of anti-dsDNA Ab (22%) and anti-CL Ab (28%) during 10 weeks of observation. In contrast SEB, TSST-1 and MAM induced a 29%, 1% and 17% reduction in the anti-DNA titers and a 32%, 15% and 12% reduction in the anti-CL titers, respectively. CONCLUSIONS: These data suggest that the SAg tested here cannot replace the effect of CFA in the induction of the primary humoral response. The SAgs TSST-1, SEB and MAM did not induce the SLE-like disease following idiotypic modulation. Moreover, they may have had a suppressive effect on the idiotypic network in our model. The appearance of anti-CL Abs in almost all the experimental groups including the naive mice supports the possibility that microbial SAgs can induce the production of autoantibodies by different mechanisms. The SAgs TSST-1, SEB and MAM reduced autoantibody production in the serologically established idiotypic-induced experimental SLE-like murine model. This beneficial effect may indicate new directions for research on the management of SLE.
Animals↗