ISSN:1524-9557    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Summary:Normal human melanocyte proliferation and differentiation is dependent on stimulation of one of three growth factor/receptor systems. They are fibroblast growth factor (FGF), hepatocyte growth factor (HGF), and mast cell growth factor (MGF), which activate the FGF receptor, c-Met, and c-Kit, respectively, known to be receptor tyrosine kinases. In contrast, human melanoma cells from primary nodular and metastatic lesions grow autonomously partially because of inappropriate production of basic FGF (bFGF) and continuous activation of the bFGF-receptor kinase. Activation of transmembrane receptor tyrosine kinases in melanocytes stimulates not only proliferation but also the expression of pigmentation. Melanoma cells constitutively express several tyrosyl-phosphorylated proteins that in normal melanocytes are stimulated in response to growth factors. This high level of phosphorylation was not due to either the presence of constitutively active Kit kinase and Met kinase nor to the absence of any of several known protein tyrosine phosphatases. Because bFGF by itself does not transform melanocytes to melanomas, there must be additional cooperating factors that confer the malignant phenotype to pigment cells.

ISSN:1524-9557    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Summary:To understand the role of individual genes in regulating biological processes, one must be able to interfere specifically with either their expression or function. While monoclonal antibodies have proven very useful in studying cell surface proteins, the specific inhibition of intracellular proteins in viable cells is a much more difficult problem. The goal of antisense technology is to develop small oligonucleotides, plasmids, or retroviral vectors that can be introduced easily into viable cells in order to inhibit gene products specifically. In this report, we will describe our use of antisense DNA and RNA to study the role of theNMYCproto-oncogene in neuroectodermal cell growth and differentiation.

ISSN:1524-9557    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Summary:While certain cytokines such as interleukin-1 (IL-1), tumor necrosis factor-a (TNF-a), IL-6, and transforming growth factor-p (TGF-p) may be involved in pro- and anti-inflammatory events in the central nervous system (CNS) of patients with multiple sclerosis (MS) and CNS acquired immunodeficiency syndrome (AIDS), there is not uniform consensus as to whether they are elevated or even detectable in all compartments of the body such as serum, cerebrospinal fluid (CSF), and tissue. Furthermore, if they are elevated in these diseases, there are no data as to whether they regulate the disease process itself. Myelin damage in MS is a punctate demyelination; in AIDS, it is a diffuse myelin pallor or dysmyelination. Oligodendrocytes are destroyed in MS but not CNS AIDS, suggesting a different mechanism for myelin loss in the two diseases. These different pathologies may provide clues about the role of macrophages, microglia, and/or the toxic products they produce in putatively giving rise to myelin damage. The stimuli that trigger such a destructive response by macrophages or glial cells and/or the regulation of the toxic events in the two diseases we would predict to be different. In MS, an effector cell-mediated lesion production and oligodendrocyte cell destruction seem to occur. We hypothesize that the effector is the inflammatory blood macrophage and/or microglial cell induced and promoted to its cytotoxic activity by a collaboration of neurotransmitters and cytokines. In CNS AIDS, virus-induced toxic products of glia and their diffusion through white and gray matter areas of the brain have been suggested. Such soluble mediators would then compromise metabolic processes of neurons and glia without widespread target cell loss.

ISSN:1524-9557    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Summary: Major humoral mechanisms include the endocrine and immune systems, and there is substantial literature describing interactions between these systems during infection and inflammatory processes. Within the brain, such interactions are less well known. One major brain function altered during infection and inflammation and by several endocrine hormones is sleep. These changes in sleep provide a useful illustration of the interactions between cytokines and the hypothalamus-pituitary axis (HPA). Experimental evidence is reviewed that illustrates the interaction of cytokines, especially interleukin-1 (IL-1), with the HPA in regard to their effect on sleep. The evidence linking IL-1, growth hormone-releasing hormone/growth hormone, and corticotropinreleasing hormone to sleep regulation is reviewed. There is also evidence that shows that these two major sleep-regulatory systems are linked to each other.

ISSN:1524-9557    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Summary:The mammalian immune system possesses the intrinsic capacity to evoke a wide variety of functionally distinct effector mechanisms following stimulation by a particular antigenic substance. Such diversity in available responses is absolutely essential to the immunocompetent host, which must continually deal with a diverse set of potential pathogens within its everchanging environment. The development of appropriate types of immune responses, therefore, represents a highly dynamic process that requires that an equivalent consideration be given to a large array of components, any one of which is capable of modulating the final outcome. While the nature and complexity of the antigen(s), plus the intracellular or extracellular mode of presentation, provide specificity and some selection to the developing process, the route of antigen entry, as well as the physiological status of the host at the time of antigen insult, also contribute significantly to the formation of any immune response. The overall objective of this article is to introduce the concept that platelet-derived growth factor (PDGF) (either preformed or synthesized in response to stimulation), plus a number of steroid hormones (some of which are end-organ metabolized at local tissue sites), can all play significant roles in the genesis of immunologic responses in vivo.

ISSN:1524-9557    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

To assess whether similar or dissimilar molecular features of class I human lymphocyte antigen (HLA) molecules determine the presentation of structurally diverse peptides, we have examined the influence of different pockets within the HLA-A2.1 molecule on the presentation of three different viral peptides. The influenza virus Ml 58-66, HTLV-I Tax peptide 12-19, and HCMV gB 619-628 are minimal peptides that induce HLA-A2.1-restricted noncross- reactive CTL responses. The influence of distinct structural features of HLA-A2.1 on peptide presentation was analyzed using a panel of 14 HLA-A2 mutants each with single amino acid substitutions in one of six pockets that are located in the peptide binding site. Ten of the 14 mutants showed concordant effects on the presentation of all three peptides to their peptide-specific CTL lines. Four of the mutants had a negative effect on the presentation of only one or two of these viral peptides. These findings indicate that common structural features in HLA-A2 determine the binding and conformation of different peptides, and help to provide a plausible explanation for how diverse peptides bind to HLA-A2.

ISSN:1524-9557    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Summary:Tumor clones isolated from the same subcutaneous metastatic lesion of a melanoma patient were used to investigate the potential role of (},- integrins (VLA) in the lysability of neoplastic cells by autologous CD3+, WT31+, CD8+cytotoxic T-cell clones. Phenotypic analysis of melanoma clones for expression of VLA molecules revealed a subset of clones with high expression of VLA-2, VLA-5, and VLA-6. This subset was also characterized by increased susceptibility to lysis by tumor-specific and nonspecific cytotoxic T-lymphocytes from either TILs or PBLs. Blocking assays with monoclonal antibodies indicated that anti-VLA-2, -5, and -6 antibodies could significantly reduce the lysis of VLA-2+, VLA-5+, and VLA-6+melanoma clones by either specific and nonspecific CTLs. By contrast, no inhibition was seen on lysis of VLA-2-, VLA-5-, and VLA-6-negative tumor cells. These data indicate that expression of some (3,-integrins on human melanoma can influence the specific and nonspecific T-cell-mediated recognition of neoplastic cells.

ISSN:1524-9557    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Primary cutaneous melanomas can be induced in inbred mice by applying a dose of dimethylbenz[a]anthracene to the skin of 4-day-old mice, and then applying repeated doses of a tumor promoter to the same site over a long period of time. Preliminary experiments suggest that the final incidence of melanomas is strongly influenced by the age at which the initiating dose of carcinogen is applied. Melanomas induced by this method in C3H mice are immunogenic and exhibit a high degree of cross-reactivity when tested by immunization and challenge in vivo. Exposing the mice to ultraviolet (UV) radiation during carcinogenesis dramatically accelerates the appearance of melanoma. We are attempting to determine how UV radiation potentiates melanoma induction by studying the growth of melanoma cells transplanted into UV-irradiated skin. Our studies suggest that UV irradiation accelerates the outgrowth of melanoma cells by means of a local, immunosuppressive effect on the skin. However, this effect is distinct from the ability of UV irradiation to alter epidermal Langerhans cells and interfere with the induction of contact hypersensitivity responses. We postulate that UV irradiation augments melanoma development by interfering with the efferent arm of the immune response in the UV-irradiated site.

ISSN:1524-9557    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Summary:This article reviews the serological analysis of cell surface antigens of chemically induced sarcomas of murine origin. This analysis, which was aimed at molecular characterization of the highly restricted tumor specific transplantation antigens of sarcomas, led to the initial biochemical identification and characterization of p53. The results of this early study clearly pointed to p53 as playing a key role in cellular proliferation and transformation. Current research of the tumor-specific or -associated antigens of chemically-induced sarcomas and melanomas of murine origin is also discussed.

ISSN:1524-9557    

出版商:OVID    

年代:1992

数据来源: OVID