Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0344329 (collapse)
 28,634 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Infection of Human organism by Human Immunodeficiency viruses induces, after a shorter or a longer period, a complex immune Deficiency (ID) that has been named Acquired Immune Deficiency Syndrome (AIDS). Although the designation is not correct, it has been accepted by the scientific community. AIDS includes multiple clinical situations that have in common HIV infection and an almost constant ID, that at the end of natural course of infection manifestated by the presence of opportunistic infections and malignant tumors. HIV-1 and HIV-2 are slow RNA viruses with a common architecture and well known genomic organization. The characteristics that made HIV infectious agent n. 1 in XXth Century are their remarkable heterogeneity, close AA sequence homology between some of their proteins and relevant molecules in human beings: MHC molecules, IL-2, VIP, etc. and a strong affinity of gp 120 to CD4 receptor of T helper lymphocytes (T4), mononuclear phagocytes, natural killer cells, etc. all of them sharing a relevant role in normal immune response (IR). Affected in its cornerstones of cellular defense, human organism starts an immune defense through antibodies, cytotoxic T Lymphocytes (CTL) Natural Killer Cells (NK) antibody dependent cell cytotoxicity (ADCC), that fails. Activating immune system HIV turn that defense strategy to their own profit and enhanced replication. After an apparent latency period--in which the balance seems to favor the host--new viral variants arise due to high rate of HIV mutagenesis, that in turn stimulate immune system, induce new cycles of viral replication and new high virulent mutants, leading to the final collapse of Immune System.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Immunologic aspects of HIV infection]. 180 34

Systemic capillary leak syndrome (SCLS) is a rare disease characterized by episodes of collapse due to rapid transfer of considerable volumes of plasma from the intravascular to the extravascular compartment. The pathogenesis of this disease is unknown. The diagnosis is made largely on clinical grounds, and investigations are unhelpful. The only consistent abnormality is that an IgG paraprotein is found in most patients, raising the possibility that the paraprotein may be involved in the pathogenesis of the disease. Reduction of the paraprotein level in our patient was associated with remission. Blood samples from three SCLS patients and one probable SCLS have been studied. All patients had monoclonal IgG paraproteins. The purified paraproteins were all of IgG1 subclass and had kappa light chains. However, they differed in size and charge. Antibodies against each of the paraproteins were raised in rabbits. Affinity-purified anti-idiotypic antibodies were tested for cross-reactivity against the other paraproteins using immunoblotting and Ouchterlony assay. These assays showed that the anti-idiotypic antibodies reacted only with the immunizing paraprotein and not with any of the other paraproteins, i.e. that the paraproteins do not share a common idiotype. Paraproteins did not bind to cultured endothelial cells, either unactivated or following activation with interferon-gamma (IFN-gamma), IL-2 or IL-6. In addition, we were unable to demonstrate any cytotoxicity towards cultured human endothelial cells by paraprotein alone, or in the presence of neutrophils (pronounced neutrophilia being a feature of attacks). The relationship between the paraproteins and the disease remains unclear. It is likely that additional, as yet unidentified, factors are required for the paraprotein to lead to capillary leak.
 ...
PMID:The paraproteins in systemic capillary leak syndrome. 837 Jan 70

Flavone acetic acid, an agent which has been implicated in both tumor vasculature collapse and NK cell activations, has been tested recently as a potential anti-cancer chemotherapeutic agent. We have tested this agent in combination with adoptive immunotherapy using IL-2 activated natural killer (A-NK) cells in a metastatic B16 melanoma model in C57BL/6 mice. By using rhodamine-labeled A-NK cells we have been able to quantitate both the number of A-NK cells that localize within each tumor section and the percentage of the tumor area occupied by A-NK cells. This has been accomplished using an image analysis system. Flavone acetic acid (200 mg/kg, i.p.) given one day prior to the injection of A-NK cells increased the area of the tumor occupied by A-NK cells and the area of individual A-NK cells approximately 2-fold; however, it did not appear to increase the number of A-NK cells per tumor cross-section. Nevertheless, this increase did not lead to any significant change in the therapeutic efficacy of A-NK cell adoptive immunotherapy. Our studies therefore suggest that mere enhancement of A-NK cell recruitment into tumor metastases does not necessarily translate into enhanced metastatic therapeutic efficacy. Moreover, this method may be a useful tool for pre-screening of compounds which enhance the accumulation of adoptively transferred cells into tumor metastases prior to in vivo screening for therapeutic efficacy.
 ...
PMID:Flavone acetic acid enhances accumulation of IL-2 activated NK cells within established metastases. 989 Dec 22

A 10-year-old male cross-breed dog was referred for investigation of oral malignant melanoma. Fine-needle aspirates were taken from the draining submandibular lymph node. The presence of metastatic melanoma cells was confirmed by cytological examination and reverse transcription polymerase chain reaction (RT-PCR) using primers for the melanoma-associated antigens: tyrosinase and mart-1/melan A. Cytokine expression in the lymph node was evaluated by multiplex RT-PCR, which demonstrated the presence of mRNA for IL-10 and TGF-beta1. However, IL-2, IL-4 and IFNgamma mRNA could not be detected, suggesting a lack of immune activation. Thoracic radiographs showed a lesion within the caudal lung fields suggestive of pulmonary metastasis. The dog developed signs of dyspnoea and collapse and was euthanased four days later. This case illustrates that molecular techniques can be used to aid clinical staging of canine oral malignant melanoma, and suggests that immunosuppressive cytokines could be involved in the pathogenesis of disease.
 ...
PMID:Immunosuppressive cytokines in the regional lymph node of a dog suffering from oral malignant melanoma. 1240 Jun 46

We have previously shown, using jasplakinolide, that stabilization of the actin cytoskeleton enhanced apoptosis induced upon cytokine withdrawal (Posey and Bierer [1999] J. Biol. Chem. 274:4259-4265). It remained possible, however, that a disruption in the regulation of actin dynamics, and not simply F-actin stabilization, was required to affect the transduction of an apoptotic signal. We have now tested the effects of cytochalasin D, a well-characterized agent that promoted actin depolymerization. Actin depolymerization did not affect CD95 (Fas)-induced death of Jurkat T cells in the time course studied but did enhance the commitment to cytokine withdrawal-induced apoptosis of factor-dependent cell lines. The induction of cell death was not the result of direct cytoskeletal collapse, since treatment of the cells with cytochalasin D in the presence of IL-2 did not promote death. As with jasplakinolide, the enhancement of commitment to apoptosis could be delayed by overexpression of the anti-apoptotic protein Bcl-x(L), but, unlike jasplakinolide, cytochalasin D modestly affected the "execution" stage of apoptosis as well. Taken together, these results suggest that changes in actin dynamics, i.e., the rate of actin polymerization and depolymerization, modulate the transduction of the apoptotic signal committing lymphocytes, withdrawn from required growth factors, to the death pathway.
 ...
PMID:Inhibition of actin polymerization enhances commitment to and execution of apoptosis induced by withdrawal of trophic support. 1261 43

In the present study, we aimed at examining the immunosuppressive activity of saikosaponin a, a triterpene saponin derived from Bupleurum falcatum L. (Umbelliferae), and the underlying mechanisms. Saikosaponin a significantly inhibited the proliferation and activation of T cells activated by concanavalin A (Con A) in a concentration-dependent manner. Additionally, it potently suppressed Con A-stimulated IL-2, IFN-gamma and TNF-alpha production in mouse T cells. Saikosaponin a also caused G0/G1 arrest of activated T cells through down-regulating the protein levels of CDK6 and Cyclin D3 and up-regulating the protein level of p27(kip). Furthermore, the compound dose-dependently induced apoptosis of Con A-activated T cells rather than those non-activated, as determined by Annexin V/PI staining. Besides, it induced a remarkable collapse of mitochondrial membrane potential and caused significant release of cytochrome c from mitochondria to cytosol. In summary, these results suggest that the G0/G1 arrest as well as the induction of apoptosis via mitochondrial pathway are involved in the immunosuppressive activity of saikosaponin a against activated T cells. This may herald a novel approach for further studies of saikosaponin a as a candidate for the treatment of inflammatory and autoimmune diseases.
 ...
PMID:Saikosaponin a inhibits the proliferation and activation of T cells through cell cycle arrest and induction of apoptosis. 1937 24