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Biomedical subjects

M Schaefer

Publications and source records attributed to M Schaefer.

At least 127 records · Page 7Linked to original sources

Capacity of purified unprimed Lyt-2+ cells to reject Ia- H-2-different tumor cells in the Winn assay.

To examine which cells participate in primary anti-H-2 responses to Ia- tumors in vivo, irradiated mice were injected intracutaneously with small doses of tumor cells mixed with purified populations of host-type lymphoid cells. Studies with three different Ia- H-2-different tumors showed that purified unprimed Lyt-2+ cells were highly efficient at suppressing tumor growth. Lyt-2+ cells were appreciably more effective at suppressing tumor growth than unseparated T cells, and no protection was seen with injection of L3T4+ cells (except in the late states of tumor growth). It is suggested that class I alloantigens on the tumors are directly immunogenic for Lyt-2+ cells. Without need for help from L3T4+ cells, the responding Lyt-2+ cells rapidly differentiate into cytotoxic cells and destroy the tumor cells before macroscopic tumors can arise.

Animals↗

Role of T cell subsets in lethal graft-versus-host disease (GVHD) directed to class I versus class II H-2 differences. I. L3T4+ cells can either augment or retard GVHD elicited by Lyt-2+ cells in class I different hosts.

Detailed information was sought on the capacity of purified Lyt-2+ cells to mediate lethal graft-versus-host disease (GVHD) directed to class I H-2 differences. When B6 Lyt-2+ cells were transferred to irradiated class I-different (B6 x bm 1)F1 mice, three different patterns of lethal GVHD were observed. First, rapid death from hematopoietic failure occurred when Lyt-2+ cells were transferred together with host-type marrow cells; this form of GVHD probably reflected direct destruction of stem cells by Lyt-2+ cytotoxic cells. Second, a pattern of late-onset, chronic GVHD resulting in death only after 4-6 wk occurred when Lyt-2+ cells were supplemented with donor marrow. This syndrome developed in the apparent absence of L3T4+ cells and was observed with either high or low doses of Lyt-2+ cells and with either light or heavy irradiation of the host. Third, an acute form of GVHD resulted when Lyt-2+ cells plus donor marrow cells were supplemented with exogenous help, i.e., by adding small doses of donor L3T4+ cells or injecting the hosts with rIL-2. Although L3T4+ cells potentiated GVHD when injected in small doses, supplementing Lyt-2+ cells with large doses of L3T4+ cells paradoxically led to marked protection; symptoms of GVHD were mild and no deaths occurred.

Animals↗

Test-retest reliability of the MSLT.

The test-retest reliability of the Multiple Sleep Latency Test (MSLT) was evaluated in 14 healthy normal subjects. Each slept a single night in the laboratory (8 h time in bed) and received the MSLT the following day (1000, 1200, 1400, and 1600 h) on two occasions separated by 4-14 months. Mean sleep latency (four tests) was highly reliable from MSLT to MSLT (r = 0.97, p less than 0.001). The test-retest reliability did not change as a function of the interval of time between tests or as a function of the level of sleepiness (range = 4-20 min) within the population. However, as the number of tests comprising the MSLT was reduced below three, the reliability was reduced such that only 50% or less of the variance could be predicted.

Adult↗

Gd-DOTA, a potential MRI contrast agent. Current status of physicochemical knowledge.

The complex (Gd-DOTA) meglumine has recently been used as an MRI contrast agent in humans. Due to its particularly interesting physicochemical properties, the risk of in vivo dissociation of the complex is reduced. Indeed, as a result of the macrocyclic nature of the DOTA ligand, Gd-DOTA appears very stable, demonstrating a calculated conditional stability constant of 10(22.19) at pH = 7. Other characteristics making Gd-DOTA a positively attractive compound include slow dissociation kinetics inherent in the rigidity of the macrocycle and marked specific affinity of DOTA for gadolinium in comparison with other endogenous ions. Finally, although the relaxivity R1 of Gd-DOTA at 20 MHz appears similar to that of Gd-DTPA, Gd-DOTA demonstrates higher paramagnetic efficacy at low field strength due to greater symmetry of the complex. Such promising properties open up wide prospects for the use of Gd-DOTA in MRI.

Contrast Media↗

[Pathology of the urachus: diagnosis and therapy].

Urachal abnormalities may provoke especially urinary tract infections. They become symptomatically first of all in the childhood. The development of urachal carcinoma is particularly described in the adult. The features of diagnosis and treatment will be presented with clinical examples. The only possible treatment of those malformations is the operative removal of the urachal tissue. This is most important to prevent as well urinary tract infections as the malignant degeneration of the urachal malformations.

Abdominal Neoplasms↗

Detection of cholecystokinin-58 in human blood by inhibition of degradation.

Although cholecystokinin-58 (CCK-58) is a major molecular form stored in the intestine, it has not yet been shown to be released into the circulation. This report describes in vitro degradation of CCK-58 in human blood and plasma and the molecular forms detected when this degradation is inhibited. After incubation of CCK-58 for 150 min between 20 and 24 degrees C, approximately 60% of immunoreactivity recovered was degraded to smaller immunoreactive forms. Storage of the 150-min incubate at -20 degrees C for 3 days greatly increased the observed degradation to 85%. When CCK-58 was added in vitro to blood, similar degradation occurred. Degradation of CCK-58 could be inhibited by addition of acid. Blood was obtained 1 h after a test meal designed to stimulate CCK release. The pH was lowered during collection and processing of blood and plasma to inhibit in vitro degradation of cholecystokinin. This method permitted the detection of significant amounts of CCK-58 in circulation.

Cholecystokinin↗

Properties of purified T cell subsets. II. In vivo responses to class I vs. class II H-2 differences.

Highly purified populations of C57BL/6 (B6) L3T4+ and Lyt-2+ T cell subsets were compared for their capacity to exert alloreactivity to class I vs. class II H-2 differences in vivo. B6 Lyt-2+ cells responded strongly to the class I different mutant, bm1, as manifested by DNA synthesis in the spleen of irradiated mice followed by entry of blast cells into thoracic duct lymph, induction of splenomegaly in newborn mice, production of lethal GVHD in irradiated mice, and skin allograft rejection. By all of these parameters, B6 Lyt-2+ cells showed almost total unresponsiveness to the class II-different mutant, bm12. Reciprocal results were observed with B6 L3T4+ cells, these cells responding strongly against bm12 but not against bm1. In the case of purified T cell subsets from other strains, CBA/Ca and B10.BR L3T4+ cells both responded well to a full H-2 difference. Responses by Lyt-2+ cells from these strains were weaker, especially for CBA/Ca cells. The implications of these findings are discussed.

Animals↗

Modulation of a respiratory motor program by peptide-secreting neurons in Aplysia.

Respiratory pumping of the gill and siphon of Aplysia californica is a fixed-action pattern coordinated by a defined set of interneurons and motor neurons. In semi-intact preparations of the gill and siphon innervated by the abdominal ganglion, respiratory pumping is facilitated for a prolonged period following activation of the peptidergic bag cell neurons. The induced changes in contractile behavior of the gill and siphon correlate with cell-specific actions of the bag cells on motor neurons regulating these organs. Our results suggest that peptidergic neurons can alter the expression of a fixed pattern of behavior by modulating the excitability of motor neurons controlling the behavior.

Animals↗

Perceptions of quality of life following divorce: a study of children's prognostic thinking.

The general quality of latency-aged children's prognostic thinking and the way in which they view the long-range impact of divorce upon peer adaptation are explored. When interviewed about responses to two fictional peers with marked behavior problems, 80 children in the third and fifth grades displayed an optimism in their prognostic thinking about the future of these peers. In general, peers from divorced homes were perceived as having a more positive future adjustment than peers from intact homes. However, male subjects from disrupted homes revealed a significantly pessimistic orientation regarding the impact of divorce upon the future; females from disrupted homes had a strikingly optimistic view. Implications for school-based interventions are discussed.

Adaptation, Psychological↗

Functions of purified L3T4+ and Lyt-2+ cells in vitro and in vivo.

The expression of L3T4 and Lyt-2 cell surface molecules separates T cells into two broad, non-overlapping subsets: typical T helper cells are L3T4+ Lyt-2- whereas most T killer cells and their precursors are L3T4- Lyt-2+. This review compares highly purified populations of unprimed L3T4+ and Lyt-2+ cells for their capacity to respond to class I vs. class II H-2 alloantigens. Various parameters are considered, including generation of mixed lymphocyte reactions (MLR) and cell mediated lympholysis (CML) in vitro, proliferative responses in irradiated mice, graft-versus-host reactions and skin allograft rejection. In all of these assays the two T cell subsets exhibit marked specificity in their response to H-2 alloantigens, L3T4+ cells responding only to class II and not class I differences and Lyt-2+ cells showing reciprocal specificity. Contrary to current dogma, the bulk of the evidence suggests that primary responses of Lyt-2+ cells do not depend on exogenous help provided by other T cells.

Animals↗

Properties of purified T cell subsets. I. In vitro responses to class I vs. class II H-2 alloantigens.

In light of the widely accepted view that Ia-restricted L3T4+ T helper cells play a decisive role in controlling the differentiation of Lyt-2+ cells, experiments were designed to examine whether Lyt-2+ cells can respond to antigen in the absence of L3T4+ cells. The results showed that highly purified Lyt-2+ cells gave high primary mixed lymphocyte reactions (MLR) to various class I differences, including both mutant and allelic differences; responses to class II (Ia) differences were generally undetectable with Lyt-2+ cells. The intensity of MLR to class I differences was not affected by addition of anti-L3T4 monoclonal antibodies (mAb) to the cultures or by removing T cells from the stimulator populations. Negative selection experiments showed that Lyt-2+ cells could respond to class I differences across Ia barriers. MLR of purified Lyt-2+ cells peaked on days 3-4 and then fell sharply; background responses with syngeneic stimulators (auto-MLR) were virtually absent. Parallel experiments with purified L3T4+ cells showed that this subset responded in MLR only to class II (Ia) and not class I differences, reached peak responses only on day 6 rather than days 3-4, and often gave high auto-MLR. Within the first 3-4 d of culture, MLR were generally higher with Lyt-2+ cells than L3T4+ cells. Although no evidence could be found that Ia-restricted L3T4+ cells were required for the response of Lyt-2+ cells, presentation of antigen by Ia+ cells appeared to be essential. Thus, responses were ablated by pretreating stimulator cells with anti-Ia mAb plus C'. Significantly the failure of Lyt-2+ cells to respond to anti-Ia plus C'-treated stimulators could not be restored by adding syngeneic spleen cells; addition of IL-2 led to only a minor (15%) restoration of the response. It is suggested that Ia+ cells provide an obligatory second signal required by Lyt-2+ cells.

Animals↗

Activity-related changes in protein phosphorylation in an identified Aplysia neuron.

The relationship between long-term electrical activity and protein phosphorylation was investigated in single, identifiable neurons in the abdominal ganglion of Aplysia californica by the intracellular injection of radiolabeled ATP followed by sodium dodecyl sulfate (SDS) gel electrophoresis. Natural and pharmacological treatments that alter the impulse activity of neurons L6 and R15 for prolonged periods did not appear to affect the phosphorylation of most of the 15 major phosphoproteins examined in these cells. Long-term excitation of L6 induced by the phosphodiesterase inhibitor IBMX correlated with phosphorylation of a 29,000-dalton protein. Long-term inhibition of L6 induced by afterdischarge of peptidergic bag-cell neurons appeared to cause dephosphorylation of a 29,000-dalton protein. Burst augmentation of R15 induced by bag-cell afterdischarge did not cause detectable changes in the phosphorylation of the major proteins we examined. These data are consistent with other studies of neural and nonneural tissues which have found a correlation between activity and the level of phosphorylation of a 29,000-dalton protein.

1-Methyl-3-isobutylxanthine↗

Low molecular weight proteins of Aplysia neurosecretory cells.

The proteins of identified cells from the Aplysia californica central nervous system were labeled with radioactive amino acids and fractionated on SDS acrylamide gels containing 6 M urea. Most of the large cells contain prominent, cell-specific protein products in the molecular weight range between 3 and 30 KD. The molecular weights of the largest specific prevalent protein products are in good agreement with the predicted molecular weights of precursors as determined from an analysis of cDNA clones homologous to mRNA's specifically expressed in several of these neurons. Biologically active peptides have been found in many of these cells. These data, and other indirect evidence suggests that the synthesis of a large amount of a particular protein in this molecular weight range is indicative of the synthesis of a neurosecretory product. We conclude that most, if not all, large neurons in the Aplysia central nervous system are peptidergic.

Animals↗

Aplysia neurons express a gene encoding multiple FMRFamide neuropeptides.

The neuroactive peptide Phe-Met-Arg-Phe-NH2 (FMRF-amide) has a variety of effects on both mammalian and invertebrate tissues; moreover, FMRFamide-like immunoreactivity is found throughout the animal kingdom. Here we describe the isolation and characterization of a cDNA clone from an Aplysia abdominal ganglion cDNA library that encodes a precursor protein that may give rise to as many as 19 individual FMRFamide peptides. Nearly all of the FMRF sequences are flanked on the amino terminus by Lys-Arg residues and on the carboxy terminus by Gly-Lys residues, suggesting that the single lysine residues function to signal cleavage by processing enzymes. The gene is present in a single copy per haploid genome and gives rise to multiple transcripts, at least some of which appear to arise through alternate RNA splicing. Immunohistochemical analysis suggests that the peptide is present in many neurons throughout the Aplysia nervous system and that these neurons send processes to a variety of different tissues.

Amino Acid Sequence↗

Affinity-purified interleukin 2 induces proliferation of large but not small B cells.

Immunoaffinity-purified interleukin 2 (IL2) stimulated proliferation of large but not small B cells. Stimulation was observed even when B cells were cultured at very low cell densities (3 X 10(4) per microwell containing 0.2 ml of medium). Addition of small numbers of purified splenic T cells did not enhance the IL2-induced B-cell proliferative response. These results suggest that IL2 was not operating through contaminating T cells. B cells cultured with anti-Ig antibody in vitro showed enhanced proliferation when cultured with EL4 thymoma-derived B-cell growth factor but not when cultured with IL2. A direct role for IL2 in B-cell activation is discussed.

Animals↗