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Biomedical subjects

W Hahn

Publications and source records attributed to W Hahn.

At least 19 recordsLinked to original sources
PubMed2004

Viral vector-mediated transduction of a modified thrombospondin-2 cDNA inhibits tumor growth and angiogenesis.

Gene therapy represents a possible alternative to the chronic delivery of recombinant antiangiogenic proteins to cancer patients. We have constructed retroviral and adenoviral vectors that express murine N-terminal fragments of thrombospondin-2 (NfTSP2), a potent endogenous inhibitor of tumor growth and angiogenesis. To test the possibility of anticancer gene therapy using NfTSP2, we tested whether an ex vivo retrovirus-mediated procedure could be used for the treatment of tumors. The treatment of tumor-bearing mice with syngenic immortalized cell lines expressing NfTSP2 led to a tumor volume reduction up to 70% as compared with the controls (P<0.005). In addition, the established tumors were eradicated in 40% of the mice treated with NfTSP2-expressing cells. Furthermore, the intratumoral injection of the NfTSP2-expressing adenoviral vector to the human squamous cell carcinoma in nude mice resulted in a significant reduction of the growth rates and the volumes of the carcinoma (P<0.05). Immunohistochemical staining of the tumors indicated that the total area and the average size of tumor vessels were significantly reduced in the treatment group versus the controls (P<0.05). In conclusion, the present study clearly demonstrates that the viral vector-mediated transfer of the NfTSP2 gene could inhibit the growth of tumors by perturbing tumor-associated angiogenesis.

Adenoviridae↗
PubMed2003

Electro-gene therapy of collagen-induced arthritis by using an expression plasmid for the soluble p75 tumor necrosis factor receptor-Fc fusion protein.

Tumor necrosis factor (TNF) is a proinflammatory cytokine involved in the pathogenesis of rheumatoid arthritis, and antagonism of TNF may reduce the activity of the disease. Among a number of techniques for gene transfer in vivo, the direct injection of plasmid DNA into muscle is simple, inexpensive, and safe. In this study, we attempted to treat collagen-induced arthritis (CIA) with anti-TNF gene therapy by transferring the plasmid encoding soluble p75 TNF receptor linked to the Fc portion of human IgG1 (sTNFR:Fc) using in vivo electroporation. DBA/1 mice were immunized with bovine type II collagen and boosted with the same antigen. At 2 days after boosting, the plasmid vector containing cDNA for the sTNFR:Fc was injected into one selected site in the gastrocnemius muscle followed by electroporation. Serum levels of sTNFR:Fc reached 2.3 ng/ml on day 5 when gene expression reached its peak. Macroscopic analysis of paws for redness, swelling and deformities showed that the onset of moderate-to-severe CIA in mice treated with sTNFR:Fc was prevented on a significant level compared with the control mice (P<0.05). The beneficial effect of sTNFR:Fc DNA transfer lasted for at least 18 days following treatment. In addition, both the synovitis and the erosion of cartilage in the knee joints were dramatically reduced in mice treated with sTNFR:Fc (P<0.05). The expression of IL-1beta and IL-12 in the paw was also decreased by sTNFR:Fc treatment (P<0.01) while there was little change in the levels of IL-17 and vWF. These data showed that sTNFR:Fc expression plasmid was effective in the prevention of CIA, and in vivo electroporation-mediated gene transfer may provide a new approach to cytokine therapy in autoimmune arthritis.

Animals↗
PubMed2003

Protection against collagen-induced arthritis by intramuscular gene therapy with an expression plasmid for the interleukin-1 receptor antagonist.

The interleukin-1 receptor antagonist (IL-1Ra) is an endogenous protein that can prevent the binding of IL-1 to its cell-surface receptors. Among a number of techniques for gene transfer in vivo, the direct injection of naked DNA into muscle is simple, inexpensive and safe. In this study, we evaluated the potential of intramuscular gene therapy with plasmid DNA containing the cDNA for IL-1Ra in the prevention of murine collagen-induced arthritis (CIA). DBA/1 mice were immunized with bovine type II collagen. At 4 weeks after the initial immunization, expression plasmid for IL-1Ra was injected into four selected sites in the thigh and calf muscles of DBA/1 mice. Control mice received the same plasmid, but lacking the IL-1Ra coding sequence. Macroscopic analysis of paws for redness, swelling and deformities showed that the onset of moderate to severe CIA in the paws of mice injected with IL-1Ra DNA was significantly prevented (P<0.05). In addition, both the synovitis and the cartilage erosion in knee joints were dramatically reduced in mice treated with IL-1Ra DNA (P<0.05). The expression of IL-1beta was significantly decreased in the ankle joints of mice treated with IL-1Ra (P<0.01). Interestingly, the levels of IL-1Ra in sera and joints after intramuscular injection of IL-1Ra DNA were significantly lower than when protein had been used in previous reports, suggesting that the therapeutic effect may be achieved by an alternative mechanism(s) rather than by systemic elevation of IL-1Ra. These observations provide the first evidence that direct intramuscular injection of expression plasmid for IL-1Ra may effectively suppress the inflammatory pathology in arthritis.

Animals↗
PubMed2000

Complications during root canal irrigation--literature review and case reports.

LITERATURE REVIEW AND CASE REPORTS: The literature concerning the aetiology, symptomatology and therapy of complications during root canal irrigation is reviewed. Three cases of inadvertent injection of sodium hypochlorite and hydrogen peroxide beyond the root apex are presented. Clinical symptoms are discussed, as well as preventive and therapeutic considerations.

Animals↗
PubMed1999

Application of a peptide bank from porcine brain in isolation of regulatory peptides.

Over the past years, the introduction of biological assay systems, random peptide sequencing and orphan receptor screening has led to the isolation and identification of new regulatory peptides with potential clinical impact. We have developed a method for separating peptides into about 300 fractions from large amounts of porcine brain tissue. The preparation of this peptide bank consists of three steps including ultrafiltration followed by cation-exchange separation and reversed-phase chromatography. These fractions represent the peptide bank with desalted and lyophilized peptides from brain tissue. Molecular masses of the peptides in the fractions are determined by matrix-assisted laser desorption ionization MS and a mass data bank is subsequently generated. For systematic analysis of the peptides, a subsequent two-step purification procedure is followed by Edman sequencing resulting in the identification of different peptides. A survival assay with a neuronal cell line revealing the stimulatory and inhibitory activities is applied as a model to test the 300 fractions. This primary screen indicates that the biological activities of the extracted peptides are easily characterized and, moreover, can be related to the biochemical entities. We conclude that the established peptide bank is an efficient and useful tool for the isolation of regulatory brain peptides applying different purification strategies.

Animals↗
PubMed1994

Determining a healthcare organization's value.

As the consolidation activity among healthcare providers increases, it becomes more important than ever for healthcare financial managers to understand how to determine a healthcare organization's fair market value. There are many methods of determining an organization's value, but three general methods are the foundation of all others: the market comparable method, the underlying assets method, and the income, or cash flow, method.

Accounts Payable and Receivable↗
PubMed1991

T7 infection-dependent selective expression of cloned genes in P1-lysogenic Escherichia coli.

Expression systems based on the selective transcription of genes cloned behind a T7 promoter, by T7 RNA polymerase, display a non-negligible basal expression when the T7 RNA polymerase gene is present within the host organism before induction of the system. This is a problem, especially for cloning and controlled expression of genes toxic to the host organism. We have circumvented this problem by taking advantage of abortive T7 infection of E. coli (P1), in the course of which T7 RNA polymerase is synthesized but bacterial growth is not quantitatively impaired. We have tested this system with three reporter genes, the 6-phospho-beta-galactosidase gene of Staphylococcus aureus, the luciferase operon of Vibrio harveyi, and the rabbit beta-globin gene; we have found very low basal levels, while, upon T7 infection, transcription is at least as efficient as in other in vivo T7 RNA polymerase systems in use.

Animals↗
PubMed1991

[Acute cor pulmonale as a sequela of tumor embolism].

It is reported on a 22-year-old female patient with a chondroplastic osteosarcoma in the sacrum in whom in the course of her disease a massive embolism due to a tumour developed under the clinical picture of an acute pulmonary embolism. The clinical tentative diagnosis of a massive pulmonary embolism was confirmed by means of lung perfusion scintigram and pulmonary angiography. All efforts for a rapid recanalisation of the left pulmonary trunk by means of mechanical alteration, use of balloon catheter and subsequent thrombolysis were without success. Pathologo-anatomically a recurred tumorous thrombus embolism with an extensive pulmonary infarction in the left inferior lobe of the lung was found. The incidence as well as diagnostic viewpoints of embolisms due to tumour are discussed.

Adult↗
PubMed1990

[Early and late results after local streptokinase administration in massive lung embolism].

In a total number of 44 patients with acute massive lung embolism 42 patients survived the acute phase. The treatment was carried out by thrombolysis with streptokinase. The application was performed as near to the thrombus as possible, in several patients after preceding balloon dilatation or also as multiphase treatment using urokinase. We altogether obtained favourable early results concerning the recanalisation got as well as also with regard to the clinical state and the subjective condition, particularly for patients with single acute occurrence and a latency period of less than 72 hours up to the beginning of the treatment. In follow-up examinations of 17 patients after more than 9 months (on an average after 32 months) without exception a good and further on ameliorated condition, respectively, was stated. Under long-term anticoagulation with phenprocoumon no recidivation embolisms appeared. Ergooxytensiometric investigations had as result a clear to extreme hypoxia on exertion as limiting factor for 12 out of 17 patients. Apart from this the majority of the patients a hyperdynamic regulatation of the circulation was to be observed. Therefore the ergooxytensiometry is recommended for the judgment of the result of the treatment as to the demandable exercise tolerance.

Adult↗
PubMed1990

[An experiment on the theory of visual motion perception].

Two classes of theories of motion perception were studied: correlation and gradient models (in the sense of D. Marr). Random-dot kinematograms with a shifted square were presented to subjects, and the 80% threshold for detection of correct direction of movement was determined. Correlation models predict scale invariance, that is, a constant shift measured in units of texture elements of the translated pattern in spite of a geometric magnification. This was refuted for all subjects. The increase of the recognizable translation with the area of the translated form was verified except for the patterns with the largest texture elements (8 minutes of arc). This prediction, however, is not very specific for competing theories. Gradient models are not yet fully specified, and they contain some free parameters. They cannot be tested strictly, but there exist reasonable numerical parameter values by which our data can be satisfactorily explained.

Adult↗
PubMed1989

[Dose-reduced antihypertensive agents--use in complex nonmedicamentous therapy of hypertension].

In order to estimate the influence of a non-medicamentous therapy (CNT) on the consumption of medicaments and coronary risk in high blood pressure 73 hypertensives of a medicamentously stabilized CNT-group were examined in comparison to a group of the same size of patients with hypertension who were managed exclusively medicamentously for behaviour of blood pressure, need of antihypertensive drugs and changes of hypertension-associated risk factors. After an exactly controlled 6-month treatment hypertensives with additionally recommended far-reaching CNT showed an economization of medicaments by scarcely the half in comparison to the reference group. By means of suitable control methods a causal non-medicamentously conditioned decrease of blood pressure could be excluded. A different need of antihypertensive drugs was simulated by the exacter intake of medicaments in the index-patients. Notwithstanding the metabolic effects of the additional therapy have induced a positive change of atherogenic lipids. The examinations indicate in general the difficulty of the judgement of efficacy of non-medicamentous therapeutic measures in connection with a rational dose-reduced long-term therapy with antihypertensive drugs.

Adult↗
PubMed1988

[Results of a 2-year intervention for the modification of atherosclerosis precursors in school children].

801 children aged 10-11 years were examined in 1984, before an allocation in two groups (intervention vs. control). The scope of the intervention was to modify mean values of blood pressure, total cholesterol and smoking through relevant modification of knowledge and behavior. An intermediate assessment, conducted 2 years after the first exam, showed better knowledge regarding cardiovascular diseases and more sport practice in the intervention group, although smoking habits were only slightly modified. Diet, body weight, blood pressure and blood lipid levels did not show any significative differences. The study is now ongoing.

Anthropometry↗