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Biomedical subjects

T Hahn

Publications and source records attributed to T Hahn.

At least 109 records · Page 6Linked to original sources

[Festival injuries. Injury patterns at the Midtfyn Music Festival in 1988].

A first-aid station was established at the Midtfyn Music Festival in 1988. A total of 174 patients were treated. The diseases and casualties are described according to numbers, distribution, course and causes. Orthopaedic casualties constituted approximately 60%, sprains, infections, contusions and open wounds being the commonest. Respiratory diseases were the commonest conditions among the non-orthopaedic conditions. Treatment could be completed in approximately 60% of the cases. Most of the casualties were caused by broken glass, deliberate violence or failure to comply with maintenance medication. Various suggestions are made to reduce the number of casualties.

Adolescent↗

[Treatment methods of keloid and hypertrophic scar formation].

Hypertrophic scar and keloid are diagnoses based on clinical symptoms. Hypertrophic scar is an unacceptably enlarged scar, within the boundaries of the original wound; whereas keloid is an unacceptably enlarged scar infiltrating the surrounding tissue. Hypertrophic scar and keloid belong to the same category of diseases, characterized by increased collagen development. The treatments employed are compression, excision, corticosteroid injections and irradiation. New medical treatments affecting the collagen metabolism such as colchicin, beta-amino-proprionitrite (BAPN), D-penicillamine, cytostatics and prostaglandin-inhibitors have been introduced with promising results and fewer side effects.

Child↗

Possible role of natural cytotoxic activity in the pathogenesis of AIDS.

In an attempt to assess the role of immune cytotoxic activity in the sequence of events leading to the acquired immunodeficiency syndrome (AIDS), natural cytotoxic activity was studied in 17 asymptomatic homosexual males, seropositive for anti-human immunodeficiency virus (HIV) antibodies, as compared to 16 of their seronegative counterparts and to 14 control healthy heterosexual individuals. Cell (contact)-mediated cytotoxicity (CMC) as well as cytotoxin (CTX) production by lipopolysaccharide (LPS)-stimulated, phytohemagglutinin (PHA)-stimulated, HeLa tumor cell-stimulated, and unstimulated peripheral blood mononuclear cells (PBMC) were determined using HeLa cell monolayer cultures, sensitized with cycloheximide, as targets. The CMC was markedly enhanced in the seropositive group (28 +/- 21 (mean +/- SD) lytic units/10(6) PBMC) as compared to the seronegative group (17 +/- 7; P less than 0.005) and to the heterosexual group (13 +/- 6; P less than 0.05). Likewise, CTX production by unstimulated PBMC from seropositive homosexuals (19 +/- 26 units/ml) was higher than that observed in the other groups (both 4 +/- 4 units/ml; P less than 0.05). CTX production by PHA-stimulated, LPS-stimulated, and HeLa cell-stimulated PBMC was significantly enhanced in both the seropositive and seronegative groups in comparison to the normal heterosexual controls. These results suggest that increased cytotoxic activity may be present in homosexuals prior to their exposure to HIV, and may be further enhanced after HIV infection.

Acquired Immunodeficiency Syndrome↗

The interferon system in subacute sclerosing panencephalitis and its response to isoprinosine.

Plasma interferon activity (IFN) and its spontaneous and stimulated production by peripheral blood mononuclear cells (PBMC) was studied in 11 patients with subacute sclerosing panencephalitis (SSPE) and age-matched healthy controls. The patients, similar to the healthy controls, had no detectable plasma IFN activity. However, their PBMC failed to produce IFN in response to stimulation with poly I:C and PHA. After isoprinosine administration to 7 patients for several days a significant increase in plasma IFN activity was observed and their PBMC responded to stimulation by producing IFN. The long-term effect of isoprinosine on the IFN response was evaluated in 3 patients who had been treated for 57-88 days. Induction of the abolished IFN production was observed with initiation of therapy. However, discontinuation of isoprinosine for 10 days resulted in recurrence of the inactivation state of the IFN system.

Adolescent↗

Interferon treatment in acute progressive and fulminant hepatitis.

A small proportion of patients with acute viral hepatitis run a progressive fulminant course ending in acute liver failure with encephalopathy, and with a mortality rate of 75-80%. In small children and pregnant women mortality is even higher. We have treated 32 patients of all ages with acute progressive and fulminant hepatitis over the last 7 years in an uncontrolled trial with human interferon-alpha (HulFN-alpha), with i.m. doses of 3 x 10(6) u/day (70,000 u/kg per day for infants) for 8 +/- 3 days (mean +/- SD.) In 17 patients hepatitis was due to hepatitis A virus, in 7 to hepatitis B virus, in 6 to non A-non B virus and in 1 case each to herpes and cytomegalovirus. Sixteen patients (50%) recovered including 9 of 22 (41%) who were in Grades III-IV coma when treatment was started. Only 1 of 8 children less than 4 years of age recovered, whereas 15 of 24 (62%) older children and adults survived. Two of three pregnant women with acute fulminant hepatitis survived. In patients who recovered, improvement was often noted on about the fifth day of IFN treatment: 9 of 16 patients died before completing 5 days of therapy. Our studies of the IFN system response to hepatitis viruses showed that the greater majority of patients produce IFN in the acute stage of the infection. However, a minority have a defective IFN response that is more severe and more common in progressive fulminant hepatitis, and in several of these patients IFN response was completely lacking. It is in these cases that IFN treatment is likely to have the greatest value. On the basis of these encouraging preliminary results, it is suggested that a well-controlled, double-blind study be done to evaluate the effectiveness of HulFN-alpha treatment when given early during the course of acute progressive viral hepatitis.

Acute Disease↗

Tumor necrosis factor in middle ear effusions.

The presence of tumor necrosis factor (TNF) was determined in middle ear effusions from 27 ears of children with chronic otitis media with effusion. Cytotoxic activity was assessed by quantitation of target (HeLa) cell death after incubation with the aspirate. Moderate cytotoxic activity was found in 17 of 27 samples (mean cell death of 53% and 32% at 1:2 and 1:4 dilutions, respectively). In ten (37%) of the middle ear effusion aspirates no cytotoxic activity was detected. To confirm that cytotoxicity was due to TNF, 13 of the samples with cytotoxic activity were incubated with a monoclonal anti-TNF antibody and retested. Cytotoxicity was blocked by the anti-TNF antibodies in all cases. Tumor necrosis factor, derived most probably from macrophages or mast cells in the middle ear, may mediate various pathologic processes associated with otitis media, such as generation of mucoid effusion, fibroblast proliferation, and bone resorption.

Child↗

Interrelated effects of tumor necrosis factor and interleukin 1 on cell viability.

Cells are sensitized to the cytolytic effect of tumor necrosis factor (TNF) by simultaneous application of inhibitors of RNA or protein synthesis. Treating cells, in the absence of such inhibitors, with cytokine preparations produced by stimulated mononuclear leukocytes may render them resistant to the cytolytic effect of TNF + the inhibitors. One of the cytokines which induces that resistance was identified as TNF itself (17). As shown in the present study, similar resistance against TNF-mediated killing can be effectively induced also with preparations of cytokines which are depleted of TNF. Fractionation of such TNF-free preparations revealed that their resistance-inducing activity is mediated by interleukin 1 (IL 1). In part of the cell lines in which IL 1 induced resistance to TNF killing, when applied without inhibitors of protein/RNA synthesis, it was found to exert cytolytic effect in the presence of such inhibitors, however, less effectively than TNF. Both TNF and IL 1 thus appear to activate in cells cytolytic mechanisms as well as antagonizing mechanisms which can protect cells from cytolysis.

Cell Line↗

Reduced production of tumor necrosis factor by mononuclear cells in hairy cell leukemia patients and improvement following interferon therapy.

In 16 patients with hairy cell leukemia (HCL) there was a marked reduction in the production of cytotoxins (CTXs) by peripheral blood mononuclear leukocytes in response to stimulation in vitro by phytohemagglutinin (PHA), 4 beta-phorbol-12-myristate-13-acetate (PMA), or Sendai virus. CTX yields of 23.5 +/- 21.5 U/ml, 15 +/- 18 U/ml, and 12.1 +/- 12.1 U/ml were obtained in response to PHA, PMA, and Sendai virus, respectively, as compared with corresponding yields of 207.3 +/- 93.1, 154 +/- 37.4, and 205.2 +/- 62.4 in healthy controls. The extent of reduced production of CTXs appeared to be correlated with the severity of the disease. Systemic interferon (IFN) administered to four patients caused CTX production to improve in response to PHA (147.5 +/- 55.1 U/ml compared with pretreatment values of 14.1 +/- 6 U/ml, P less than 0.05). However, CTX production in response to Sendai virus remained low. The extent to which CTX production by hairy cell leukemia mononuclear cells was reduced was proportionate to the observed decrease in monocyte counts. However, the degree to which CTX production improved after IFN treatment was significantly greater than the observed increase in monocyte counts. The major CTX induced by PHA in mononuclear cells of healthy donors and of IFN-treated HCL patients was identified as tumor necrosis factor-alpha.

Adult↗

Selection for phenylalanine hydroxylase activity in cells transformed with recombinant retroviruses.

Cells deficient in phenylalanine hydroxylase (PAH) are tyrosine auxotrophs and will not survive in tyrosine-free media. PAH activity can be constituted in cultured cells by infection with recombinant retroviruses carrying a human PAH cDNA. Mouse hepatoma cells transformed with recombinant PAH will grow in tyrosine-free media since these cells constitutively synthesize the cofactor tetrahydrobiopterin which is essential for PAH activity. NIH3T3 cells transformed with the PAH cDNA express the PAH apoenzyme, but this enzyme is inactive in vivo since these cells do not synthesize biopterin. We describe a method of selection for PAH in the fibroblast-like NIH3T3 cells involving tyrosine-free media supplemented with biopterin, reducing agents, and antioxidants. Cells transformed with the recombinant PAH gene exhibit PAH activity in culture and will grow in the biopterin-supplemented tyrosine-free media. Metabolic selection for PAH activity provides a new selectable marker for gene transfer experiments. This method is shown to be useful in the production of high titers of recombinant retroviruses carrying PAH and provides a model for experiments in somatic gene therapy of phenylketonuria.

Animals↗

Retroviral gene transfer into primary hepatocytes: implications for genetic therapy of liver-specific functions.

The liver is an important target for potential gene therapy because of the critical role it plays in intermediary metabolism and synthesis of serum proteins. We report the use of retroviral vectors for transfer of recombinant genes into primary mouse hepatocytes. Hepatocytes were grown in a defined serum-free medium and expressed liver-specific functions for up to 14 days. Hepatocytes were transformed to Genticin (G418) resistance by infection with recombinant retroviruses carrying the Tn5 neomycin-resistance gene. The G418-resistant cells exhibited characteristic hepatocyte morphology and continued to express liver-specific gene function. A retrovirus that expresses neomycin resistance driven by a herpes simplex thymidine kinase promoter produced the most efficient transformation compared with viruses using the retroviral long terminal repeat promoter or the simian virus 40 early-region promoter. These experiments indicate that primary hepatocytes can be successfully cultured and transformed with recombinant genes using retroviral vectors. These results provide a model for future somatic gene replacement therapy in which functional genes can be introduced into hepatocytes by viral-mediated gene transfer.

Animals↗

Tumor necrosis factor induction by Sendai virus.

Supernatants of peripheral blood mononuclear leukocytes (PBMC) treated with Sendai virus were found to exert significant cytotoxic effects mediated by leukocyte-produced proteins distinct from interferon. Fractionation of the PBMC into adherent and nonadherent cells indicated that these virus-induced cytotoxins (CTX) were produced primarily in the mononuclear phagocytes. Cells of the monocyte-like U937 line pretreated with 4 beta-phorbol-12-myristate-13-acetate could also be induced with Sendai virus to produce CTX. The nonadherent mononuclear cells of the peripheral blood responded poorly to the virus with regard to CTX production, even though they could be induced to produce CTX with phytohemagglutinin (PHA). With the use of monospecific antibodies to tumor necrosis factor (TNF) and to lymphotoxin (LT), it was found that TNF is the major CTX produced by PBMC and by the U937 cells after 24 hr stimulation by the virus, whereas LT is not induced under these conditions to any measurable extent. TNF was also found to be produced in significant amounts together with LT upon stimulation of the nonadherent fraction of the PBMC by PHA. These findings indicate that besides bacterial lipopolysaccharides, other biological agents including viruses can be effective inducers of tumor necrosis factor, suggesting implications regarding the physiologic role of this protein.

Cell Adhesion↗

Binding of human TNF-alpha to high-affinity cell surface receptors: effect of IFN.

Human tumor-necrosis factor (INF-alpha), induced by Sendai virus in peripheral blood mononuclear leukocytes (PBMC), was isolated using a monoclonal antibody to the protein and radioiodinated by the chloramine-T method. Effective labelling of the protein with little loss of bioactivity was obtained. The labelled protein was found to bind specifically to high affinity receptors present on cells of various cultured lines. The molecular nature of these receptors was examined using the bifunctional cross-linking reagents disuccinimidyl suberate (DSS) and dithiobis succinimidyl propionate (DSP). In SDS-PAGE, conjugates between TNF receptors and the labelled TNF of two sizes (about 75 and 92 kDa) were detected. 125I-labelled TNF was also used to examine variations in TNF receptor concentration, upon treatment of cells by interferon (IFN) or TNF, and any correlation of observed variations with the effect of IFN and TNF on responsiveness of cells to the cytotoxicity of TNF. The decreased vulnerability of cells to the cytotoxic effect of TNF, following treatment of cells by TNF itself, was not correlated with decreased availability of free receptors for the protein. However, an increase in responsiveness of cells to TNF following treatment by IFN was accompanied by some increase in binding of TNF to the receptors.

Cell Line↗

Bacterial colonization and occurrence of Legionella pneumophila in warm and cold water, in faucet aerators, and in drains of hospitals.

Warm and cold water as well as water from wash basin drains and faucet aerators was examined to determine the number of viable and dead bacteria by culture and by staining and to establish the spectrum of species with special consideration of Legionella pneumophila. The relation between the number of Legionella pneumophila, the temperature, and the iron content of the water was determined in three separate warm water systems. High colony counts (up to 8.9 X 10(5) colony-forming units), were detected in both warm and cold water at certain sampling sites. The most prevalent genera were Pseudomonas, Bacillus, Flavobacterium, Acinetobacter, and Moraxella. Legionella pneumophila was found in every building in 35 of 150 warm samples and in 1 of 43 cold water samples. The highest water temperature of a sample containing Legionella pneumophila was 64 degrees C. The correlation between high colony counts and the occurrence of Legionella pneumophila in the samples was not significant. High iron concentrations, however, appear to have a positive effect on the growth of Legionella pneumophila.

Equipment and Supplies, Hospital↗