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At least 19 recordsLinked to original sources
PubMed2025

AlphaFold2, SPINE-X, and Seder on Four Hard CASP Targets.

We analyzed four cases from the CASP15 experiment with low prediction accuracy and compared AlphaFold2, SPINE-X, and Seder on these cases. We find that overall, AlphaFold2 performs better than SPINE-X in predicting secondary structure (SS) and solvent accessible surface area (ASA). For some cases, SPINE-X better predicts sheet and coil regions. We also find that AlphaFold2 is better than Seder in selecting the best matching tertiary structure model for one case and is worse in another case. For two cases Alphafold2 and Seder selected the same models. From the cases presented here, it appears that AlphaFold2 predicts more compact structures than the native one. We find that while, as widely reported, AlphaFold2 significantly improved protein tertiary structure prediction, there are cases, such as the four presented here, for which the tertiary structure prediction could still be significantly enhanced. The source code, license, and documentation for SPINE-X and Seder are available from Research and Information Systems, LLC at http://mamiris.com .

Software↗
PubMed1979

A family myth: sex therapy gone awry.

The treatment of sexual disorders has achieved considerable popularity and respectability within the mental health profession and the lay community. As a consequence, it has become increasingly difficult to elude requests for this type of treatment and even more difficult to balance sexual concerns with the numerous other modes of relating that exist within a dyadic relationship. This paper will report two versions of a case study in which sexual dysfunction served as a myth that was carefully constructed to veil certain more fundamental problems.

Adult↗
PubMed1987

Tumor regression and temporary restoration of immune response after plasmapheresis in a patient with recurrent oral cancer.

A major response to plasmapheresis is reported in a patient with advanced, recurrent squamous cell cancer of the oral cavity, similar to that previously reported in three of six comparable patients. Tumor regression followed temporary reduction of inhibition of normal lymphocyte response to phytohemagglutinin (PHA) by the patient's serum (from 99% to zero) and partial restoration of the patient's lymphocyte response (from 2% to 38% of control). The IgE level rose both overall and during some exchanges; this correlate of tumor response had been noted earlier. The tumor showed extensive necrosis, but the clinical effects were relatively short-lived and the patient died 11 weeks later. Biopsy specimens taken early in apheresis showed intense new infiltration of tumor by lymphocytes and monocytes; later biopsy specimens showed predominantly plasma cells with trapping and lysis of tumor cells. No other anti-cancer therapies had been used for 16 months before this trial, and no replacements were given other than saline and albumin.

Antigens, Surface↗
PubMed1991

Increased frequency of interleukin 4-producing T cells as a result of polyclonal priming. Use of a single-cell assay to detect interleukin 4-producing cells.

A limiting dilution assay capable of detecting interleukin 4 (IL4) production by a single cell has been developed. This assay is based on the stimulation of T cells, in the presence of IL2 (5 U/ml), with anti-CD3 antibody bound to the surface of Terasaki wells. Cells of the IL4-selective indicator line, CT.4S, are added 24-36 h later and IL4 production is determined based on their survival 24-48 h thereafter. A frequency of 0.98 was obtained for IL4 production by T cells of the D10.G4 cell line. T cells from naive donors capable of producing IL4 in response to anti-CD3 plus IL2 were quite rare, with a frequency in four experiments ranging between 0.0003 and 0.0018. Treatment of mice with polyclonal activators known to increase the IL 4-producing capacity of T cells when assayed in bulk culture caused striking increases in the frequency of IL4-producing cells. Similarly, culturing cells in vitro with anti-CD3, IL2 and IL4 for 5 days caused a marked increase in the frequency of cells capable of producing IL4, to 0.031.IL4 production by individual T cells is dependent upon IL2. Thus, in naive T cell populations, the frequency of IL4-producing cells in response to stimulation with anti-CD3 in the absence of IL2 was below the limit of detection. T cells from primed donors showed a striking inhibition in the frequency of IL4-producing cells in response to anti-CD3 when IL2 was not present. The availability of a simple assay to measure the frequency of cells capable of producing IL4 should have substantial utility in allowing the evaluation of conditions that regulate IL4 production in vivo and in vitro.

Animals↗
PubMed1985

Plasma exchange in six patients with advanced cancers of the head and neck.

Six patients with advanced squamous cell cancers of the head and neck, with serum IgA greater than or equal to 400 mg/dl and IgE less than or equal to 1000 IU/ml, underwent a trial of six 2-liter plasma exchanges over a 2-3-week period. Disease progressed in patients 1, 2, and 4, who died on days 44, 72, and 159. The tumor in patients 3 and 6 regressed significantly, repeatedly in patient 3 over each of four courses of apheresis. Tumor recurred in both patients after cessation of treatment, and they died at days 420 and 79. Patient 5, with inoperable disease, received full-dose radiotherapy immediately following the course of apheresis, and showed complete response in the primary lesion and a major response in the extensive lymph node metastases, dying on day 421 of apparently unrelated causes. Serum IgE in the three patients experiencing tumor regression rose paradoxically during plasmapheresis. Only patient 3 had an elevated level of soluble E-receptor suppressor factor prepheresis; the serum of patient 6 was lymphocytotoxic prepheresis but this activity decreased or disappeared during each of the exchanges studied. Controlled trials are now indicated.

Aged↗
PubMed1987

Utilization review and quality assurance: staying in the black and working with the blues.

Utilization review (UR), Quality Assurance (QA), and Peer Review (PR) have become essential aspects in the practice of general hospital psychiatry. This article first defines and elaborates the basic elements of UR, QA, and PR and then outlines the development of a program for these professionally initiated and maintained methods of problem seeking and solving as it occurred on a short-term voluntary inpatient psychiatric unit. Finally, current trends and conflicts inherent to QA, UR, and PR are discussed, with a view towards the future.

Cost Control↗
PubMedDate not supplied

Prevalence of aortic regurgitation by color flow Doppler in relation to aortic root size.

To determine whether there is a correlation between aortic root size and the prevalence of aortic regurgitation, we performed color flow Doppler echocardiographic studies on 1015 consecutive patients during a 3-month period. Patients were grouped according to their M-mode aortic root diameter as measured in the left parasternal position. The measured groups ranged from 2.0 to 4.5 cm, grouped at 0.1 cm intervals. As the aortic root size enlarged, the prevalence of aortic regurgitation increased linearly (p less than 0.001; correlation coefficient, r = 0.75). At an aortic root size in the "small normal" range of 2.0 to 2.4 cm, the prevalence of aortic regurgitation was 0% to 15%. In the "intermediate" and "top normal" ranges of 2.9 to 3.7 cm, the prevalence of aortic regurgitation increased linearly from 15% to 47%. With aortic root dilation, the prevalence of aortic root regurgitation was generally more than 50%. The severity of aortic regurgitation was semiquantified. Aortic root size was not a good indicator for the severity of aortic regurgitation. Patients with moderate and severe aortic regurgitation had variable aortic root sizes. Throughout the range of aortic root sizes, mild aortic regurgitation predominated. We conclude that aortic regurgitation is a common finding in patients with aortic roots that are dilated or are in the "top normal" size range, that the prevalence of aortic regurgitation increases linearly with aortic root size, and that aortic root size does not correlate with the severity of aortic regurgitation.

Aorta↗
PubMed1991

Mouse splenic and bone marrow cell populations that express high-affinity Fc epsilon receptors and produce interleukin 4 are highly enriched in basophils.

Splenic and bone marrow cells from normal mice, and from mice that have been polyclonally activated by injection of anti-IgD antibody, contain cells that produce interleukin 4 (IL-4) in response to crosslinkage of Fc epsilon receptors (Fc epsilon R) or Fc gamma R or to ionomycin. Isolated Fc epsilon R+ cells have recently been shown to contain all of the IL-4-producing capacity of the nonlymphoid compartment of spleen and bone marrow. Here, purified Fc epsilon R+ cells are shown to be enriched in cells that contain histamine and express alcian blue-positive cytoplasmic granules. By electron microscopy, the vast majority of cytoplasmic granule-containing cells are basophils; they constitute approximately 25% and approximately 50%, respectively, of Fc epsilon R+ spleen and bone marrow cells from anti-IgD-injected mice. The Fc epsilon R- populations contain cells that form colonies typical of mast cells. The Fc epsilon R+ populations also contain cells that, upon culture with IL-3, form colonies of alcian blue-positive cells, but (in contrast to colonies derived from Fc epsilon R- populations) the colonies are small, and all the cells die within 2-3 weeks. The Fc epsilon R+ cells synthesize histamine during a 60-hr culture with IL-3, while the Fc epsilon R- cells do not. These results indicate that IL-4-producing Fc epsilon R+ cells are highly enriched in basophils.

Animals↗
PubMed1990

Generation of interleukin 4 (IL-4)-producing cells in vivo and in vitro: IL-2 and IL-4 are required for in vitro generation of IL-4-producing cells.

T cell populations derived from naive mice produce very small amounts of interleukin 4 (IL-4) in response to stimulation on anti-CD3-coated dishes. IL-4 production by such cells is mainly found among large- and intermediate-sized T cells and is dependent upon IL-2. Injection of anti-IgD into mice, a stimulus that leads to striking increases in serum levels of IgG1 and IgE, causes a striking increase in the IL-4-producing capacity of T cells. This increase is first observed 4 d after injection of anti-IgD. IL-4 production by T cells from anti-IgD-injected donors is mainly found among large- and intermediate-sized T cells. Small, dense T cells are poor producers of IL-4. The capacity of T cells from anti-IgD-injected donors to produce IL-4 is enhanced by addition of IL-2 and is largely, but not completely, inhibited by neutralization of in situ produced IL-2. These results indicate that the control of IL-4 production in T cells from naive and anti-IgD-injected donors is similar. However, it is possible that a portion of the IL-4-producing activity of T cells from activated donors is IL-2 independent. Although small T cells from naive donors have a very limited capacity to produce IL-4 in response to stimulation with anti-CD3, even in the presence of added IL-2, they can give rise to IL-4-producing cells upon in vitro culture on plates coated with anti-CD3 if both IL-2 and IL-4 are added. This leads to the appearance of IL-4-producing cells within 2 d. When analyzed after 5 d of culture by harvesting and re-exposure to anti-CD3-coated culture wells and IL-2, these cells have increased their IL-4-producing capacity by approximately 100-fold. The development of IL-4-producing cells in response to anti-CD3, IL-2, and IL-4 is not inhibited by interferon gamma (IFN-gamma), nor does IFN-gamma diminish IL-4 production by these cells upon challenge with anti-CD3 plus IL-2.

Animals↗
PubMed1992

Activation events during thymic selection.

During their differentiation in the mouse thymus, CD4+8- cells undergo several of the sequential changes observed upon normal activation of mature, peripheral CD4+ lymphocytes. Expression of CD69, an early activation marker, is first observed on a minority of cells at the T cell receptor (TCR)lo/med double-positive stage, is maximal (50-90%) on heat-stable antigen (HSA)hi TCRhi double-positive, HSAhi TCRmed CD4+8lo, and HSAhi TCRhi CD4+8- cells, and is downmodulated at the mature HSAlo CD4+8- stage. In contrast, CD44, a late activation marker, is selectively expressed at the HSAlo stage. The set of lymphokines that CD4+8- thymocytes can produce upon stimulation also characteristically expands from mainly interleukin 2 (IL-2) at the HSAhi stage, to IL-2 and very large amounts of IL-4, IL-5, IL-10, and interferon gamma (IFN-gamma) at the HSAlo stage. 1 in 30 HSAlo CD4+8- adult thymocytes secrete IL-4 upon stimulation through their TCR. This frequency is 25% of the frequency of IL-2 producers, about 100-fold above that of peripheral (mainly resting) CD4+ T cells. With time after their generation in organ culture, CD4+8- thymocytes lose their capacity to secrete IL-4, IL-5, and IFN-gamma, but not IL-2. Similarly, the frequency of IL-4, but not of IL-2, producers progressively decreases after emigration to the periphery as judged by direct comparison between thymic and splenic CD4+ cells in newborns, or by following the fate of intrathymically labeled CD4+8- cells in adults after their migration to the spleen. This sequence suggests that thymic selection results from an activation process rather than a simple rescue from death at the double-positive stage, and shows that the functional changes induced after intrathymic activation, although transient, are still evident after export to the periphery.

Animals↗
PubMed1992

The presence of interleukin 4 during in vitro priming determines the lymphokine-producing potential of CD4+ T cells from T cell receptor transgenic mice.

To study the factors that determine whether CD4+ T cells produce interleukin 4 (IL-4) or interferon gamma (IFN-gamma) upon stimulation we used a system allowing naive T cells to be primed in vitro by specific antigen. Dense CD4+ T cells were purified from mice that expressed transgenes encoding a T cell receptor specific for pigeon cytochrome C peptide 88-104 in association with I-Ek. These T cells produced very limited amounts of IL-4 and IFN-gamma upon immediate challenge with 88-104 and antigen-presenting cells (APC). However, after an initial "priming" culture in which they were incubated for 4 d in the presence of 88-104, APC, and 1,000 U/ml IL-4, the T cells acquired the capacity to produce substantial amounts of IL-4 upon rechallenge but made very little IFN-gamma. Cells primed in the absence of IL-4 produced IFN-gamma upon rechallenge but virtually no IL-4. The inhibitory effect of IL-4 on IFN-gamma production did not appear to be mediated by the induction of IL-10 production since IL-10 addition to initial cultures did not suppress priming for IFN-gamma production, nor did anti-IL-10 block the inhibitory effect of IL-4. IFN-gamma itself did not increase priming for IFN-gamma production, nor did anti-IFN-gamma reduce such priming. IFN-gamma did, however, diminish priming for IL-4 production when limiting amounts of IL-4 (100 U/ml) were used in the initial culture. The dominant effect of IL-4 in determining the lymphokine-producing phenotype of primed cells was observed with dendritic cells (DC), activated B cells, and I-Ek-transfected fibroblasts as APC. However, the different APC did vary in their potency, with DC being superior to activated B cells, which were superior to transfected fibroblasts.

Amino Acid Sequence↗
PubMed1991

Production of interleukin-4 and other cytokines following stimulation of mast cell lines and in vivo mast cells/basophils.

Interleukin-3 (IL-3)-dependent mast cell lines, upon stimulation by calcium ionophores or by Fc epsilon RI cross-linking, express mRNA for, and secrete, a distinct pattern of cytokines, similar to those secreted by cloned mouse T cells of the TH2 type. The mast-cell-derived cytokines include IL-3, IL-4, IL-5 and IL-6. Not only in vitro mast cell lines, but also in vivo derived peritoneal mast cells secrete cytokines. An in vivo derived cell, in mouse spleen and bone marrow, secretes IL-4 and other cytokines upon stimulation with calcium ionophores or by Fc epsilon RI cross-linking or Fc gamma RII cross-linking. The IL-4-producing cells are highly enriched in the Fc epsilon R+ subset of spleen and bone marrow cells. These Fc epsilon R+ cells produce large amounts of IL-4, and they have characteristics similar to those of immature mast cells and/or basophils. It is possible that cytokines produced by mast cells and/or basophils participate in allergic inflammatory diseases.

Animals↗