Continuous progress has been achieved during recent decades in the therapy of metastasizing malignancies by improving chemotherapeutic strategies and new approaches in radiation therapy. Genetic ...manipulation of tumor cells and of the tumor fighting immune system is hoped to add significant contributions to curative interventions in disseminated tumors. That we are still far from eradicating death by malignant growth is due ultimately to our limited understanding of the cascade of events resulting in metastasis formation, which until recently was believed to rely on multiple rounds of mutation and selection processes. This implies an individually specific history of each metastatic tumor, which would rule out uniform diagnostic and therapeutic concepts. When it was noted in a rat tumor model that the transfer of cDNA of a single gene, a CD44 variant isoform (CD44v) covering the exons v4-v7, sufficed to initiate metastasis formation of a locally growing tumor, hope was created that a "metastogene" may have been identified. Although the idea of CD44v expression as a unifying concept for tumor progression was not sustained, the discovery of CD44v-initiated metastatic spread allowed a conceptually new hypothesis on tumor progression as a consequence of the reactivation of genetic programs of ontogeny, stem cell differentiation, and/or lymphocyte activation. Since distinct CD44 isoforms play an important role in these processes, unraveling the functions of this family of molecules can indeed provide a cornerstone in the understanding of tumor progression. This article summarizes briefly the present knowledge on known functions of CD44 isoforms with particular focus on parallels between physiological programs and tumor progression.
Recently, we have described a panel of metastasis-associated antigens in the rat, i.e., of molecules expressed on metastasizing, but not on nonmetastasizing tumor lines. One of these molecules, ...recognized by the monoclonal antibody D6.1 and named accordingly D6.1A, was found to be abundantly expressed predominantly on mesenchyme-derived cells. The DNA of the antigen has been isolated and cloned. Surprisingly, the gene product proved to interfere strongly with coagulation. The 1.182-kb cDNA codes for a 235-amino acid long molecule with a 74.2% homology in the nucleotide and a 70% homology in the amino acid sequence to CO-029, a human tumor-associated molecule. According to the distribution of hydrophobic and hydrophilic amino acids, D6.1A belongs to the tetraspanin superfamily. Western blotting of D6.1A-positive metastasizing tumor lines revealed that the D6.1A, like many tetraspanin molecules, is linked to further membrane molecules, one of which could be identified as α6β1 integrin. Transfection of a low-metastasizing tumor cell line with D6.1A cDNA resulted in increased metastatic potential and provided a clue as to the functional role of D6.1A. We noted massive bleeding around the metastases and, possibly as a consequence, local infarctions predominantly in the mesenteric region and all signs of a consumption coagulopathy. By application of the D6.1 antibody the coagulopathy was counterregulated, though not prevented. It has been known for many years that tumor growth and progression is frequently accompanied by thrombotic disorders. Our data suggest that the phenomenon could well be associated with the expression of tetraspanin molecules.
An adult male mandrill (Mandrillus sphinx) suffered from chronic ulceration of the facial and gluteal skin and the oral and nasal mucosa. The ulcers were resistant to therapy and led to deterioration ...in the general condition of the animal. Microscopical examination revealed a severe, chronic, multifocal, granulomatous and eosinophilic dermatitis and panniculitis. There was also stomatitis and rhinitis with numerous intralesional fungal elements. These organisms were identified by immunohistochemistry, transmission electron microscopy, polymerase chain reaction and fungal culture as Candida albicans. Species identification was confirmed by MALDI-TOF mass spectrometry. A specific predisposing immunosuppressive factor for the deep chronic mucocutaneous candidiasis was not identified; however, social stress and/or a primary defect in cell-mediated immunity could not be excluded as possible causes for a predisposing immunodeficiency in the animal.
Electroconvection of liquid crystals does not only lead to a large variety of spontaneously formed patterns, but these patterns can also be used as a template for the fabrication of polymer surfaces ...exhibiting a periodic bold relief. Here, a useful room-temperature nematic mixture consisting of two photostable liquid crystals and a photosensitive cross-linker is presented. Its stability diagram in the frequency-voltage plane, the influence of monomer concentration and the topography of the resulting polymer surfaces are described.
Objectives – To examine neuropsychological deficits in adults with Neurofibromatosis type 1 (NF1) with and without an affective mental disorder (i.e. dysthymia). Material and methods – Seventy adult ...NF1 patients were followed‐up after a 12‐year period. Of 65 patients assessed earlier with the Comprehensive Psychopathological Rating Scale (CPRS), 19 patients had died. The remaining patients were assessed by the CPRS with the exception of 4 patients, and were psychiatrically diagnosed according to DSM III‐R. Twelve patients were excluded because of advanced age, and psychiatric illness other than affective disorder. The remaining 30 NF1 patients (7 with affective disorder and 23 psychiatrically healthy), and a control group of 23 normal adults were assessed on a variety of neuropsychological tests. Results – Results indicated NF1‐related deficits in inductive reasoning, visuoconstructive skill, visual and tactual memory, logical ion, coordination, and mental flexibility, although basic motor speed and vocabulary were not affected by NF1. An affective disorder exacerbated the neuropsychological deficits associated with NF1 only with regard to tests assessing motor functions. Conclusions – NF1 results in a relatively global cognitive impairment among adults, and additional depressive symptoms appear to slow down basic motor processes. It was speculated that the NF1‐related cognitive deficits may partly result from white‐matter lesions in subcortical brain areas, due to proliferation of glial tissue, aberrant myelination or hamartomas.
The melanoma-associated Ag glycoprotein 100 was analyzed by the T cell epitope prediction software TEPITOPE. Seven HLA-DR promiscuous peptides predicted with a stringent threshold were used to load ...dendritic cells (DC), and induction of a proliferative response was monitored. PBMC of all nine donors including two patients with malignant melanoma responded to at least one of the peptides. The proliferative response was defined as a Th response by the selective expansion of CD4(+) cells, up-regulation of CD25 and CD40L, and IL-2 and IFN-gamma expression. Peptide-loaded DC also initiated a T helper response in vivo (i.e., tumor growth in the SCID mouse was significantly retarded by the transfer of PBMC together with peptide-loaded DC). Because the use of the TEPITOPE program allows for a prediction of T cell epitopes; because the predicted peptides can be rapidly confirmed by inducing a Th response in the individual patient; and because application of peptide-loaded DC suffices for the in vivo activation of helper cells, vaccination with MHC class II-binding peptides of tumor-associated Ags becomes a feasible and likely powerful tool in the immunotherapy of cancer.
The impact of neurofibromatosis type 1 (NF1) on psychiatric symptoms and diagnoses, personality variables and self evaluation was studied in a 12 year-follow-up of patients with NF1 in the city of ...Göteborg, Sweden.
48 living adult patients with NF1 were re-evaluated in 1990 in a 12 year long time follow up study. The patients were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders. The following scales were used; the Comprehensive Psychopathological Rating Scale (CPRS), the Karolinska Scales of Personality inventory (KSP) and the Self-Evaluation Scale (SES).
A significant psychopathology was found in the NF1 patients,
p<0.001. One third of the patients were affected by a psychiatric disease, 21% by dysthymia. There was no significant progress in psychiatric symptoms in the follow up period. The personality profile disclosed a heightened self-esteem.
The chronic stigmatizing character of NF1 may be the reason for the increased psychopathology found.
Purpose
In Europe, intravenous fosfomycin (IV) is used particularly in difficult-to-treat or complex infections, caused by both Gram-positive and Gram-negative pathogens including multidrug-resistant ...strains. Here, we investigated the efficacy and safety of intravenous fosfomycin under real-life conditions.
Methods
Prospective, multi-center, and non-interventional study in patients with bacterial infections from 20 intensive care units (ICU) in Germany and Austria (NCT01173575).
Results
Overall, 209 patients were included (77 females, 132 males, mean age: 59 ± 16 years), 194 of which were treated in intensive care (APACHE II score at the beginning of fosfomycin therapy: 23 ± 8). Main indications (± bacteremia or sepsis) were infections of the CNS (21.5%), community- (CAP) and hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP, 15.3%), bone and joint infections (BJI, 11%), abdominal infections (11%), and bacteremia (10.5%). Most frequently identified pathogens were
S. aureus
(22.3%),
S. epidermidis
(14.2%),
Enterococcus
spp. (10.8%),
E. coli
(12.3%) and
Klebsiella
spp. (7.7%). At least one multidrug-resistant (MDR) pathogen was isolated from 51 patients (24.4%). Fosfomycin was administered with an average daily dose of 13.7 ± 3.5 g over 12.4 ± 8.6 days, almost exclusively (99%) in combination with other antibiotics. The overall clinical success was favorable in 81.3% (148/182) of cases, and in 84.8% (39/46) of patients with ≥ 1 MDR pathogen. Noteworthy, 16.3% (34/209) of patients developed at least one, in the majority of cases non-serious, adverse drug reaction during fosfomycin therapy.
Conclusion
Our data suggest that IV fosfomycin is an effective and safe combination partner for the treatment of a broad spectrum of severe bacterial infections in critically ill patients.
Co-op Cincy is an incubator of worker- and community-owned cooperatives, including the farm and food hub Our Harvest. The incubator is part of the innovative
1worker1vote.org
network of unionized ...worker cooperatives stemming from a partnership between the Spanish Mondragon Cooperatives and the United States Steelworkers. This Community Case Study examines Co-Op Cincy’s food sector organizing as an example of resistance to the industrial, corporate food system. Their hybrid and experimental approach creatively re-imagines both cooperative ownership and localist food systems. Whereas some local efforts fail to address questions of social justice or drift from social justice missions, this essay describes how Co-Op Cincy and Our Harvest 1) define their social justice goals in pursuit of locally rooted ownership, 2) raise consciousness about the connections among food systems and racial and class disparities as well as the need for sustainability, solidarity, and democratic ownership, and 3) embody these commitments in everyday organizing. Their experimentation lends insights into potential paths to create a more equitable food system and a more just economy.
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