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A Weinmann

Publications and source records attributed to A Weinmann.

9 recordsLinked to original sources
PubMed2006

Histone deacetylase inhibition by valproic acid down-regulates c-FLIP/CASH and sensitizes hepatoma cells towards CD95- and TRAIL receptor-mediated apoptosis and chemotherapy.

Hepatocellular carcinoma (HCC) is highly resistant to chemotherapy, leading to a poor prognosis of advanced disease. Inhibitors of histone deacetylase (HDACi) induce re-differentiation in tumor cells and thereby re-establish sensitivity towards apoptotic stimuli. HDACi are entering the clinical stage of tumor treatment, and several substances are currently being tested in clinical trials to prove their efficacy in the treatment of leukemias and solid tumors. In this study, we investigated the impact of the HDACi valproic acid (VA) on TRAIL- and CD95-mediated apoptosis in hepatoma cells, as well as its sensitizing effect on a chemotherapeutic agent. Treatment of HepG2 cells with VA increased sensitivity to CD95-mediated apoptosis (4% apoptosis vs. 42%), and treatment with epirubicin (74% vs. 90% viability). Caspase-3 activity was significantly enhanced in cells treated with VA plus anti-CD95 antibodies compared to cells treated with antibodies alone. In parallel, VA strongly augmented the effect of TNF-related apoptosis-inducing ligand (TRAIL or Apo2 ligand) on HepG2 cells (10% vs. 58% apoptosis). VA induced down-regulation of cellular FLICE-inhibitory protein (c-FLIP/CASH, also known as Casper/iFLICE/FLAME-1/CLARP/MRIT/usurpin), providing a possible molecular mechanism underlying the increased sensitivity towards cell death-mediated apoptosis. HDAC inhibitors are a promising class for the treatment of leukemias. In addition, among other class members, VA deserves further evaluation as a treatment option for patients with advanced HCC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Stress protein/peptide complexes derived from autologous tumor tissue as tumor vaccines.

Vaccination of inbred mice with tumor-derived stress proteins hsp70, hsp90, and gp96/grp94 elicits a protective immunity to the tumor from which the vaccine was purified. There is now comprehensive experimental evidence that the antigenicity of tumor-derived hsp70, hsp90, and gp96 preparations results from diverse arrays of endogenous peptide antigens complexed with these stress proteins. Vaccination with tumor-derived stress protein/peptide complexes leads to their uptake and processing by professional antigen-presenting cells and to presentation of associated tumor peptide antigens to cytotoxic T cells. This induces a tumor-specific cytotoxic T cell response. The attractiveness of the concept of using tumor-derived stress proteins as vaccines is derived from two observations: (i) tumor stress protein vaccines mirror the individual antigenicity of a tumor, which results from random mutations due to genetic instability; and (ii) stress proteins represent powerful adjuvants for the peptide antigens complexed to them.

Animals↗
PubMed1996

TAP-polymorphisms in juvenile onset psoriasis and psoriatic arthritis.

Juvenile onset psoriasis is strongly associated with the HLA-class I genes Cw6 and B57 whereas patients with psoriatic arthritis show an increased frequency of HLA-B27. It is unclear whether additional major histocompatibility genes also increase disease susceptibility. The TAP genes (transporter associated with antigen processing) encode two membrane-spanning proteins that translocate antigenic peptides from the cytoplasm into the endoplasmic reticulum. Comparison of 60 patients with juvenile onset psoriasis, 63 psoriatic arthritis patients, and 101 caucasoid controls revealed an increase of the TAP1*0101 allele in the psoriasis group, that could not be explained by linkage to other investigated HLA genes. There were no differences for TAP2 alleles.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Autopsy-identified infections among bone marrow transplant recipients: a clinico-pathologic study of 56 patients. Bone Marrow Transplantation Team.

We reviewed the autopsy records of 56 patients who had undergone BMT at the Detroit Medical Center during 1988-1992. Most patients (43 of 56) had died within 2 months of BMT. One or more infections were identified at autopsy in 25 of 40 (63%) allogeneic and four of 16 (25%) autologous BMT recipients. Microorganisms isolated at autopsy were cytomegalovirus (CMV) (14 patients), yeasts (13 patients), molds (aspergillus six patients, mucor one patient) and bacteria (seven patients). Presence of infection was not identified or proven prior to death in nine of 14 patients (65%) with CMV, six of 13 patients (46%) with yeasts and four of six patients (67%) with aspergillus. Most bacterial infections (five of seven patients) were identified ante-mortem. Lungs and the gastrointestinal tract were the organ systems mostly involved in patients with or without autopsy-identified infections. Pathologic findings in the lungs were diffuse alveolar damage, interstitial pneumonia and bronchopneumonia and, in the gastrointestinal tract, were ulcerations and hemorrhages of esophagus, stomach, small and large intestines. Examination of the heart showed non-bacterial thrombotic endocarditis (NBTE) in five patients, four with right-sided involvement only. Failure to identify non-bacterial pathogens ante-mortem and their frequent association with mortality in bone marrow transplant patients are high-lighted in the present study.

Adolescent↗
PubMed1993

Endocarditis following skin procedures.

Four cases of infective endocarditis following skin procedures are reported. Three of these patients had known cardiac valve abnormalities. None received antibiotic prophylaxis and three of the patients died. Prophylaxis should be considered for patients with known cardiac abnormalities before skin procedures are undertaken.

Acupuncture Therapy↗
PubMed1990

Infectious diseases. Meningococcemia.

Late last year there was an increase in meningococcal disease in Melbourne and the author reviews the treatment procedures at the Alfred Hospital, Melbourne. The article is reprinted from the Alfred Hospital's Newsletter, which is edited by Dr Denis Spelman, Physician in Bacteriology.

Anti-Bacterial Agents↗