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Biomedical subjects

C Haas

Publications and source records attributed to C Haas.

At least 73 records · Page 4Linked to original sources
PubMed1997

Virus potentiation of tumor vaccine T-cell stimulatory capacity requires cell surface binding but not infection.

This study elucidates a basically new mechanism of function of a virus-modified tumor cell vaccine which has been successful in mouse tumor models (metastatic ESb lymphoma and B16-F10 melanoma) in preventing or delaying metastatic spread and improving survival and which is being tested in clinical studies. Modification of tumor cells by a low dose of Newcastle disease virus (NDV), which caused this therapy effect, led to an augmentation of the tumor-specific cytotoxic CD8 T-cell (CTL) response and to increased CD4 T-helper activity in the absence of an antiviral T-cell response. When various noninfectious NDV preparations, which, according to newly established quantitative tests, had lost one or several of the viral functions, were tested, noninfectious virus particles with inactive fusion proteins and virus inactivated by UV light, which could fuse but could not replicate, were as active as infectious NDV in the tumor-specific CTL response. In contrast, NDV inactivated by heat treatment (NDV-HI) had no effect on the CTL response. NDV-HI, even when added to the cultures in excess, did not modulate the antitumor CTL response, which argues against a nonspecific adjuvant effect. There was no mitogenic effect of NDV. Because NDV-HI was not able to bind to the tumor cell surface and because hemagglutinin-neuraminidase c-DNA transfectants increased antigen-presenting function as virus-modified cells do, we propose that the NDV effect in the CTL response is caused by the introduction of functional viral hemagglutinin-neuraminidase molecules (1000 per virus particle) into the tumor cell surface, thereby facilitating cell-cell interactions through their cell-binding and neuraminidase activity.

Animals↗
PubMed1996

[Withdrawal syndrome in 2 drug addicts after intravenous injection of buprenorphine?].

Adequate dosage of sublingual buprenorphine is now recommended for substitution treatment of severe opioid dependance. We report two cases of acute discomfort, probably linked to withdrawal syndrome, after an IV injection of high doses of buprenorphine in opiate dependant patients. Data on the pharmacokinetics and neurobiochemical aspects of buprenorphine are compared with those of other opiates. A major issue of this work is a guideline for inducing substitution treatment with this "unique" partial agonist/antagonist of endorphinic receptors.

Acute Disease↗
PubMed1996

Immunogenicity increase of autologous tumor cell vaccines by virus infection and attachment of bispecific antibodies.

A new type of cancer vaccine for therapeutic application in cancer patients is described. It consists of three components. (1) autologous tumor cells, (2) Newcastle Disease Virus (NDV), to be used for infection and (3) bispecific antibodies (bsAb) which attach to the viral hemagglutinin neuraminidase (HN) molecule on the infected tumor cells. A standardized procedure has been developed for generating virus infected human autologous tumor cell vaccines (ATV-NDV) which includes cell dissociation, removal of leukocytes and cell debris, gamma-irradiation and cryopreservation. Infection with the non-virulent strain NDV Ulster is performed within 30 min of co-incubation. While virus infection already increased immunogenicity of the tumor vaccine, further augmentation of T cell stimulatory capacity is achieved by attachment of specially designed bi-specific antibodies (bs HN x CD28 or bs HN x CD3).

Antibodies, Bispecific↗
PubMed1996

Antibodies to human brain spectrin in Alzheimer's disease.

We investigated the existence of antibodies in sera of Alzheimer's disease patients which immunoreact with specific antigens from crude human brain extracts. We found that 49% of patients, per only 5% of control subjects, had increased levels of antibodies to a 240 kDa protein. On the basis of immunological criteria and internal amino acid sequencing, this antigen was identified as brain spectrin, a cytoskeletal protein which appears to be implicated in synaptic plasticity. Our data raises the possibility that anti-spectrin antibodies could be implicated in Alzheimer's disease pathogenesis.

Adult↗
PubMed1996

Survival, regeneration and sprouting of central neurons: the rat septohippocampal projection as a model.

The septohippocampal projection was used to study the survival following axotomy, axonal regeneration, and sprouting of a defined group of central neurons. Septohippocampal projection neurons in adult rats were axotomized by bilateral lesions of the fimbria-fornix. Using prelabeling prior to axotomy, intracellular staining, electron microscopy, and immunocytochemical and in situ hybridization techniques, we were able to demonstrate that the majority of septohippocampal neurons survived after axotomy. At least in young postnatal rats, these axotomized neurons have the capacity to regenerate an axonal process that reinnervates its appropriate target tissue, the hippocampus. We demonstrated this by axotomizing young septohippocampal neurons and co-culturing them with sections of hippocampus. Septohippocampal neurons appear to retain their capacity for axonal growth in adulthood, since they are able to sprout within hippocampal layers partially denervated by removing entorhinal afferents. In this paradigm the terminals of septohippocampal neurons themselves were not lesioned. Our results point to a previously underestimated capacity of septohippocampal neurons for survival following axotomy, regeneration, and sprouting.

Acetylcholinesterase↗
PubMed1996

Angiotensin-converting enzyme inhibition in experimental in-situ immune complex glomerulonephritis: influence on renal function, proteinuria, and morphology.

BACKGROUND: Converting enzyme inhibition (CEI) ameliorates progressive loss of function in non-immune-mediated renal diseases and experimental hypertension. Little, however, is known on the potential role of CEI in established experimental chronic glomerular immune injury. We therefore studied the effect of the CEI ramipril on renal function and morphology in a model of immune mediated glomerular injury. METHODS: The immune complex glomerulonephritis was induced in uninephrectomized rats by intrarenal perfusion with the cationized antigen followed by an intravenous application of the antibody. This disease is characterized by the development of progressive albuminuria and a nephrotic syndrome (albuminuria: immune complex glomerulonephritis 342 +/- 58, control 76 +/- 18 mg/24h; P < 0.001). The CEI by ramipril, dissolved in the drinking water, was given 28 weeks after induction of the disease and treatment was continued for 12 weeks. RESULTS: In these experiments ramipril significantly reduced albumin excretion (immune complex glomerulonephritis + CEI 109 +/- 16 mg/24h; P < 0.01) when compared with untreated nephritic rats. Ramipril, however, did not significantly change inulin clearances (immune complex glomerulonephritis 224 +/- 67, immune complex glomerulonephritis + CEI 278 +/- 48 microliters/min/100 g bw). Glomerular structural damage expressed as glomerular damage index was significantly greater in rats with immune complex glomerulonephritis when compared with controls (immune complex glomerulonephritis 0.91 +/- 0.13; control 0.60 +/- 0.08; P < 0.05), but was uneffected by the treatment with the CEI (immune complex) glomerulonephritis + CEI 1.02 +/- 0.26; control + CEI 0.63 +/- 0.11). CONCLUSIONS: These data demonstrate that ramipril reduced albuminuria in a model of immune complex glomerulonephritis; however, it failed to alter GFR and glomerular damage index. The study suggests that ramipril ameliorates proteinuria independently of obvious glomerular histological changes. The reduction of proteinuria is, however, associated with a significant decrease in filtration fraction and therefore is at least partially haemodynamically mediated.

Albuminuria↗
PubMed1996

[Is surgical therapy of distant metastases of malignant melanoma worthwhile?].

Distant metastases of malignant melanoma are generally considered as incurable related with an unfavourable prognosis. On the basis of our retrospective analysis of surgical treatment, subgroups of patients could be identified showing a significant improvement in survival after complete surgical removal of metastases. In single cases, survival longer than 10 years was observed. The surgical therapy of distant metastases of malignant melanoma is based on a strict patient selection and is only advantageous to those patients whose tumor tissue can be removed completely.

Female↗
PubMed1996

[Curative interventions for recurrence of gastrointestinal carcinomas--incidence and prognosis].

Locoregional relapse following curative resection (= R0) of gastrointestinal cancer occurs in 30% (colorectal carcinoma) and up to 70% (ductal pancreatic cancer) of patients. A potential, complete removal of a tumor recurrence can be achieved, in particular, in the case of colorectal carcinoma. For these tumors and all their locations (loco-regional, metachronic liver and lung metastasis), 5-year survival rates can amount up to 40%. The survival rates of our own patients are presented.

Follow-Up Studies↗
PubMed1995

Location of an epitope shared by Alzheimer's amyloid peptide and brain creatine kinase using a newly developed monoclonal antibody.

Amyloid plaques, composed mainly by a peptide termed A4-amyloid, derived by proteolytic processing from the amyloid precursor protein (APP), are a hallmark in the brain of Alzheimer's disease patients. We have prepared a collection of monoclonal antibodies as tools to study APP expression and proteolysis in different systems. One of these, 5AH10, raised against residues 9-22 of A4-peptide, was selected for its ability to recognize only A4 subpeptides having the intact APP-secretase target sequence, as well as whole recombinant APP. By using synthetic subpeptides, we have located 5AH10 epitope between amino acids 15 and 22 of A4. In addition, 5AH10 showed a strong immunoreactivity to a 47 kDa protein present in rat brain extracts, that was identified as the B (brain specific) subunit of creatine kinase by immunochemical data and direct N-terminal sequencing. The cross-reaction observed is most probably due to a high degree of sequence identity between amino acids 15 to 22 of A4 peptide and amino acids 9 to 16 of rat B creatine kinase. 5AH10 did not recognize the muscle specific isoform (M subunit) of rat creatine kinase, nor the B subunit of human and rabbit creatine kinase, suggesting that glutamine at first position of the epitope is essential for antigen recognition by 5AH10.

Alzheimer Disease↗
PubMed1995

MHC antigens in interferon gamma (IFN gamma) receptor deficient mice: IFN gamma-dependent up-regulation of MHC class II in renal tubules.

MHC class II gene products in parenchymal cells, such as tubular epithelial cells in kidney, may play a role in the regulation of autoimmune reactions. Expression of MHC class II in renal tubular cells is normally very low, but it increases considerably under various pathologic conditions. The predominant role of IFN gamma in up-regulation of MHC class II expression has been demonstrated repeatedly. We tested the existence of alternative pathways of MHC class II regulation using IFN gamma receptor-deficient (IFN gamma R-/-) mice. Mutant and wild type mice received 50 micrograms bacterial endotoxin (LPS) i.p. Four days later the kidneys were removed for immunofluorescence examination. In agreement with published results LPS provoked an increase of immunoreactivity for MHC class I and MHC class II in proximal tubules of wild type mice. While MHC class I up-regulation was strictly IFN gamma receptor-dependent, up-regulation of MHC II was still evident in mutant mice, although less than in wild type mice. Since injection of IFN gamma induced proximal tubular MHC class II expression in wild type mice but not in IFN gamma R-/- mice, an alternative signaling pathway for IFN gamma does not seem to exist. Thus, up-regulation of MHC class II expression in renal tubules does not necessarily require IFN gamma. The markedly patchy pattern of immunofluorescence in IFN gamma R-/- mice suggests that induction of MHC class II after LPS injection may represent renal injury due to shock.

Animals↗
PubMed1995

Astrocytes and microglia as potential targets for calcitonin gene related peptide in the central nervous system.

Injury of peripheral motoneurons leads to the activation of astrocytes and microglia in the vicinity of the damaged neurons in the central nervous system. It has been proposed that neuropeptides such as the calcitonin gene related peptide (CGRP), which show an increased expression in motoneurons following axotomy, play a role as signalling molecules mediating the interactions between the damaged neurons and surrounding glial cells. Evidence supporting this hypothesis is provided by in vitro investigations of the actions of neuropeptides on glial cells. CGRP induces activation of both astrocytes and microglia at the transcriptional level, as seen by the stimulation of mRNA for the immediate early gene, c-fos, in these cells in culture. In addition to its stimulation of immediate early gene expression, treatment of astrocyte cultures with CGRP stimulated release of the tissue plasminogen activator and led to the accumulation of mRNAs for tissue plasminogen activator and the plasminogen activator inhibitor 1. These components of the plasminogen activator system, which has been implicated in processes of tissue remodelling, are upregulated in astrocytes in the facial nucleus in vivo after facial nerve axotomy. The data suggest a role for CGRP as a mediator of glial cell activation following motoneuron injury.

Animals↗