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At least 163 records · Page 9Linked to original sources

CD8+ T cells can be primed in vitro to produce IL-4.

IL-4 production by T lymphocytes from naive mice in response to stimulation by plate-bound anti-CD3 is concentrated among CD4+ T cells. In vitro stimulation of lymph node T cells with anti-CD3 plus IL-2 and IL-4 strikingly increases the frequency of cells that produce IL-4 in response to subsequent stimulation with anti-CD3 plus IL-2. Separation of these primed cell populations into CD4+ and CD8+ T cell by cell sorting reveals that the frequency of IL-4-producing cells in both population is similar. Verification that CD8+ T cells produce IL-4 is provided by the capacity of anti-IL-4 mAb to inhibit the response of the indicator cell line to the growth factor produced by the primed cells and by detection of IL-4 by an IL-4-specific ELISA. The in vitro "priming" of CD8+ T cells to produce IL-4 is not dependent on the presence of CD4+ T cells because highly purified CD8+ T cells can be stimulated to develop into cells capable of producing IL-4 by culture with plate-bound anti-CD3 plus IL-2 and IL-4.

Animals↗

A 45-year-old man with a lung mass and history of charcoal aspiration.

A 45-year-old man was seen in consultation for evaluation of a spiculated right-lower-lobe mass that enlarged over 1 year. The patient had suffered accidental instillation of activated charcoal into the right lung via nasogastric tube 2 years prior to this consultation, with resultant respiratory failure, pneumonia, and pneumothorax. Biopsy of the mass showed anthracosis and granulomatous inflammation. A positron emission tomogram was strongly positive at the lesion, and right-lower-lobectomy with partial diaphragmatic resection was performed. On gross examination of the mass, a charcoal concretion was evident. Histologic examination showed intrinsic and surrounding granulomatous inflammation, but without tumor. The patient recovered uneventfully, and after 1 year had not experienced further complications.

Anthracosilicosis↗

Acute phase reactants and suppressive E-receptor factor in various groups of patients receiving autolymphocyte therapy.

The levels of selected acute phase proteins (APP) and of tumor-associated suppressive E-receptor factor (SER) were determined in sequential serum specimens from (1) cancer patients under treatment with autolymphocyte therapy (ALT) or plasmapheresis, (2) patients with acute infections, (3) patients with autoimmune disorders, and (4) other nonmalignant diseases. The absolute serum levels of APP, including SER, and their patterns of change over time are shown to differ significantly between cancer and non-cancer patients. The absolute levels of APP and the patterns of change over time appear to be useful indicators of immune status and predictors of antitumor response to autolymphocyte (and possibly other anti-cancer) therapy.

Acute-Phase Proteins↗

Purified Fc epsilon R+ bone marrow and splenic non-B, non-T cells are highly enriched in the capacity to produce IL-4 in response to immobilized IgE, IgG2a, or ionomycin.

Non-B, non-T cells from spleen and bone marrow cells produce IL-4 in response to cross-linkage of high affinity receptors for Fc epsilon R or Fc gamma RII, and to treatment with calcium ionophores. Cells bearing high affinity Fc epsilon R constituted 1 to 2% of non-B, non-T cells of spleen and of total bone marrow cells from naive donors. In mice whose immune systems had been polyclonally activated by injection with anti-IgD antibodies or had been infected with Nippostrongylus brasiliensis larvae, the frequency of Fc epsilon R+ cells in splenic non-B, non-T cells was also 1 to 2% but in bone marrow from anti-IgD-injected mice donors the frequency was approximately 5%. Cell sorting experiments revealed that all of the capacity to produce IL-4 in response to immobilized IgE or IgG2a or to ionomycin was found in the Fc epsilon R+ fraction. Among the Fc epsilon R+ spleen cells from naive donors, the frequency of IL-4-producing cells was 1/20 to 1/40 whereas in mice that had been injected with anti-IgD or infected with N. brasiliensis, the frequency of IL-4 producing cells in the Fc epsilon R+ population was approximately 1/5.

Animals↗

Quality assurance and managed mental health care.

Quality assurance demands that health professionals meet the timeless mandate of helping (when we can) and doing no harm. The delivery of quality care has been profoundly influenced by systems of managed care, which may represent the principal trend in organized medicine in the 1980s. This chapter first defines quality and quality assurance. We then define managed care and managed mental health care. The implications of managed care on patients and health professionals are then addressed. Finally, we discuss examples of what has been done and what can be done to help ensure the continued provision of quality care in a cost-conscious society.

Delivery of Health Care↗

The NZB X SWR model of lupus nephritis. I. Cross-reactive idiotypes of monoclonal anti-DNA antibodies in relation to antigenic specificity, charge, and allotype. Identification of interconnected idiotype families inherited from the normal SWR and the autoimmune NZB parents.

The incidence of lupus nephritis is low in autoimmune NZB mice, but when they are crossed with normal SWR mice, almost 100% of the female F1 hybrids (SNF1) develop lethal glomerulonephritis. In a previous study we showed that anti-DNA auto-antibodies produced by the SNF1 mice were qualitatively different from those made by the NZB parents with respect to their isotype, charge, and antigenic specificity patterns. Here we studied idiotypic cross-reactions among the 65 monoclonal anti-DNA antibodies that were derived from four NZB and seven SNF1 mice. A library of 15 anti-idiotypic antibodies were prepared by immunizing rabbits with 15 monoclonal anti-DNA antibodies selected from the panel of 65. We identified 10 cross-reactive idiotype (CRI) families among this large collection of autoantibodies. Five of these CRI families were restricted to cationic anti-DNA antibodies that were exclusively of SNF1 origin, and the strongly cross-reacting members were predominantly IgG2b auto-antibodies with the allotype of the normal SWR parent. The cationic anti-DNA CRI families could be grouped into an interrelated cluster called the Id564 cluster. The other five anti-DNA CRI families were not restricted to any particular parental allotype or charge, although two of these CRI were shared exclusively by SNF1-derived autoantibodies and four of these CRI families could also be grouped into an idiotypically interrelated cluster called the Id512 cluster. In the case of seven out of the 10 CRI families, the idiotypic determinants detected were close to the antigen-binding site of the anti-DNA antibodies. The results indicate that the idiotypic repertoire of anti-DNA autoantibodies produced by the SNF1 mice is different from the NZB parents, and potentially pathogenic (cationic) antibodies produced by the SNF1 mice that are encoded by genes from the normal SWR parent can be identified as distinct CRI families. In the accompanying paper we demonstrate the role of these anti-DNA CRI families in the development of lupus nephritis.

Animals↗

Studies on the metabolic origin of a glucose-containing tetrasaccharide in human urine.

Urinary excretion of a glucose-containing tetrasaccharide, Glc alpha 1-6l alpha 1-4Glc alpha 1-4Glc, designated (Glc)4, is elevated in patients with glycogenoses and other conditions in which glycogen is stored in abnormally large amounts. We have studied the time course of appearance of (Glc)4 during digestion of glycogen by salivary alpha-amylase over a wide range of enzyme/substrate ratios. Aliquots taken from digests at various times of incubation were chromatographed on Bio-Gel P-2 and (Glc)4 was determined in column fractions by radioimmunoassay (RIA) or gas chromatography. (Glc)4 is released by treatment of glycogen with salivary alpha-amylase even at very low enzyme/substrate ratios (0.017 units/25 mg glycogen). At high enzyme/substrate ratios (55 units/25 mg glycogen) release of (Glc)4 is much more rapid but remains incomplete even after 82 h. The rate of release of (Glc)4 from glycogen is about 3 times faster for whole human serum than for an equivalent amount of purified human salivary alpha-amylase. Higher alpha-limit dextrins resistant to digestion by purified human salivary and pancreatic alpha-amylases are converted to (Glc)4 without accumulation of malto-oligosaccharides. These results suggest that both alpha-amylase and neutral alpha-1,4 glucosidase in human serum act upon glycogen and its branched amylolytic cleavage products to release (Glc)4. The amount of (Glc)4 normally excreted in urine per 24 h (0.1-2.5 mg) can be accounted for by intravascular degradation of approximately 30 mg of glycogen, an amount equivalent to 0.01% of total body glycogen stores.

Borohydrides↗

Effects of interleukin-3 with or without the c-kit ligand, stem cell factor, on the survival and cytoplasmic granule formation of mouse basophils and mast cells in vitro.

We assessed the ultrastructure and the cell-surface expression of receptors for immunoglobulin E (Fc epsilon R), and c-kit, the receptor for stem cell factor (SCF), in mouse basophils and mast cells present in short-term cultures of mouse bone marrow cells in interleukin-3 (IL-3) with or without SCF. Basophils did not develop increased numbers of cytoplasmic granules and underwent apoptosis in cultures containing IL-3 and SCF, whereas mast cells thrived and developed increased numbers of granules. Basophils were nearly all Fc epsilon R+ c-kit- when sorted after culture in IL-3 and SCF; most mast cells were Fc epsilon R+ c-kit+. However, a second population of Fc epsilon R+ c-kit- mast cells was present after culture in IL-3 and SCF. These c-kit receptor-negative mast cells were less mature than c-kit+ mast cells and contained significantly fewer cytoplasmic granules than the c-kit+ mast cells present in the same cultures (P < 0.001). Thus, mouse basophils express little or no c-kit receptor on their surface, nor can they survive for long periods in SCF-supplemented cultures. By contrast, mouse mast cells seem to express the Fc epsilon R early in their development, even before they express detectable c-kit receptors on their surface. IL-3 promotes cytoplasmic granule formation in immature mast cells, but even more granules are formed when c-kit receptor-positive immature mast cells are cultured in both SCF and IL-3.

Animals↗