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T Hahn

Publications and source records attributed to T Hahn.

At least 145 records · Page 8Linked to original sources

Assay of an interferon-induced enzyme in white blood cells as a diagnostic aid in viral diseases.

Interferon is part of the system of defence against viral infections and has important cell-regulatory and immunoregulatory functions. It is, however, not always possible to quantify circulating interferon in patients. An assay has been developed to measure an interferon-induced enzyme in white blood cells. The activity of this enzyme is constant in healthy subjects but increases by 2-10 times in 85% of patients with acute viral infections. It is also enhanced in autoimmune diseases and in virus-related malignancies and neurological disorders. The enzyme level was not raised in bacterial infections or non-infectious diseases studied. This simple and rapid biochemical assay of the interferon system could be used for diagnosis and evaluation of many diseases.

2',5'-Oligoadenylate Synthetase↗

A comparison of the antiproliferative and antiviral activities of alpha-, beta- and gamma-interferons: description of a unified assay for comparing both effects simultaneously.

An assay system is described which allows simultaneous measurement of antiviral (AV) and antiproliferative (AP) activities of various interferons (IFNs) with the same indicator cells and tests one biological function, i.e. the reduction of DNA synthesis. Human IFN-alpha, -beta, and -gamma preparations were investigated for their respective AV and AP activities. In repeated independent experiments the AP:AV ratio was found to be constant for each IFN preparation. However, striking difference in the AP:AV ratios was found between the preparations, being highest in IFN-gamma and lowest in IFN-alpha. The validity of this assay was substantiated by the observation that the AP activity of the IFNs is not influenced by virus once the cells are protected by sufficient amounts of IFN and that the score of the microscopically assessed cytopathic effect (CPE) strongly correlates with the reduction of [3H]TdR uptake in the cultures. The AP:AV ratio of a Corynebacterium parvum induced IFN resembled that of the IFN-alpha-reference, suggesting that contrary to previous reports, the C. parvum induced is of alpha type. It is suggested that the assay system presented here provides a simple means not only of comparing AP and AV ratios of various IFNs but also of characterizing IFNs of unknown type.

Cell Division↗

Monitoring of interferon therapy by assay of (2'--5') oligo-isoadenylate synthetase in human peripheral white blood cells.

With the increasing number of patients undergoing experimental interferon therapy, there is a need for a method for monitoring how the patients respond to the drug. Interferon induces in cells exposed to it the accumulation of several enzymes, among them the (2'-5') oligo-A synthetase. A simple method previously developed was used to measure this enzyme in extracts of a small number of peripheral white blood cells. In 60 healthy volunteers, the enzyme level in the mononuclear cell fraction was found to be relatively high and constant. Daily intramuscular injections of 1--2 x 10(6) units leukocyte type interferon (IFN-alpha) increased the enzyme level 7--8 fold in mononuclear cells and in granulocytes. The enzyme stayed high until IFN injections were stopped. Patients with defective response to IFN were identified. We propose that this method be used for continuous monitoring of the patient's response whenever interferon therapy is undertaken.

2',5'-Oligoadenylate Synthetase↗

Evaluation of the human interferon system in viral disease.

The interferon (IFN) system in man regulates viral replication, cell multiplication and immune functions. Its action against viruses takes place in two stages. The first is the production of IFN by cells following stimulation by a variety of IFN inducers including viruses, and the second is the action of this IFN on other cells inducing in them an antiviral state which prevents replication of infecting viruses. A series of assays is described which evaluates these different parameters of the antiviral IFN system. An attempt was made to correlate between IFN production and cell response to IFN on the one hand, and clinical status on the other. Results show that healthy persons have little or no IFN in the blood (mean less than 4 units/ml), and that in 94% their PBMC are not in an antiviral state. On the other hand, patients with acute viral diseases have significantly increased levels of IFN in their blood (mean 150 +/- 284 units/ml), and in 70% their cells are in an antiviral state. In some seriously ill patients with viral disease, the IFN system was found to be functionally deficient and treatment with human leucocyte IFN rapidly changed this. It is concluded that the examination of several biological parameters of the IFN system including the intracellular antiviral state induced by IFN is necessary in order to better evaluate this antiviral system. This will enable the clinician to obtain optimal pharmacokinetic information for determining which cases are most likely to respond to IFN therapy, and help to monitor the efficacy of this treatment.

Adolescent↗

Production of immune and viral interferon by lymphocytes of newborn infants.

The ability of lymphocytes from newborn infants to produce two types of interferon was compared with that of lymphocytes from older children and adults. Cord blood lymphocytes were as capable of producing both viral interferon (stable at pH 2.0) following stimulation with polyriboinosinic acid-polyribocytidilic acid and immune interferon (unstable at pH 2.0) following stimulation with phytohemagglutinin as lymphocytes from older individuals. In a mixture of mononuclear and polymorphonuclear cells, it was the former that produced the interferon. Interferon may be important in the defense mechanism of the newborn infant against viruses and other microbial agents.

Adult↗

Effect of thymic humoral factor on cellular immune factors of normal children and of pediatric patients with ataxia telangiectasia and Down's syndrome.

Cellular immune functions of nine Down's syndrome patients and of nine was Ataxia telangiectasia vs. nine normal children and nine cord bloods, were evaluated using in vitro assays of peripheral blood lymphocytes. The in vitro assays included E rosette formation, antilymphocytic cytotoxicity by an antithymic antiserum and leukocyte migration inhibition factor (LIF) production. The mitogens and antigens used were phytohemagglutinin, purified protein derivative, and monilia antigen. The effect of a thymic hormone (THF) on these parameters was evaluated and it was administered therapeutically to three Down's syndrome patients and to two patients with Ataxia telangiectasia. Most deficient T-cell functions were reversed to normal after incubation of the lymphocytes with THF, or after THF therapeutic administration. In two Down's syndrome cases, the clinical course was not altered by THF administration, while one seemed to benefit from it markedly. One of the Atactic patients recovered from a severe viral infection, while the other died from intractable bronchopneumonia.

Ataxia Telangiectasia↗

Thymic deficiency in Down's syndrome.

Children with Down's syndrome (DS) often have small and abnormal thymuses, with lymphocyte depletion, diminution of the cortex, and loss of corticomedullary demarcation--a picture resembling thymic involution. Besides this, they have markedly enlarged Hassall's corpuscles, some surrounded by a sheath of lymphocytes. Patients with DS are known to have increased numbers of respiratory infections; they also have a higher incidence of lymphatic leukemia than do individuals who do not have DS. Studies of cell-mediated (thymic-dependent) immunity demonstrate that children with DS have both diminished numbers of T cells as well as functional deficiency of these cells.

Child↗

Immune deficiency of T system with possible T cell regulatory activity defect.

The occurrence of T system immunodeficiency in an infant together with excessive production of IgM and, to a lesser degree, of IgG and IgA, is an unusual combination. A case is reported in which an unremitting lung infection with lymphadenopathy and hepatosplenomegaly developed in a previously healthy two-month-old infant. Leukocytosis with lymphocytosis, monocytosis and eosinophilia was rapidly followed by leukopenia and lymphocytepenia after a blood transfusion for anemia. There was a transient clinical remission, but on relapse 10 days later, quantitative and functional T cell deficiency was found together with increased IgG and IgA and with IgM values reaching 50 times greater than normal. Thymic humoral factor was successful in vitro in increasing the number of identifiable T cells (E rosetts) as well as T cell function (leukocyte migration inhibition factor production). However, the infant died suddenly, and at autopsy evidence of a generalized inflammatory reaction compatible with a viral infection was found. The thymus was small, hypoplastic and hypocellular. It is speculated that the T system deficiency may have been acquired following Epstein-Barr virus infection, and that T cell regulatory activity of immunoglobulin production was defective.

Antibodies, Viral↗

Competition by 24,25-dihydroxycholecalciferol in the competitive protein binding radioassay of 25-hydroxycalciferol.

24,25-dihydroxycholecalciferol (24,25-(OH)2D3) is equipotent to 25-hydroxycholecalciferol in the displacement of 3H25-OHD3 from rat serum binding sites, and is extracted by the ethanol procedure recommended in non-chromatographic competitive protein binding radioassays for 25-OHD. Serum 24,25-(OH)2D content was measured following 24,25-(OH)2D3 isolation from lipid extracts by liquid-gel partition chromatography. Since normal serum 24,25-(OH)2D concentration is appreciable, non-chromatographic 25-OHD assays most probably overestimate serum 25-OHD levels as a result of their recognition of 24,25-(OH)2D3.

Animals↗

Leucocyte migration inhibition factor (LIF) production by lymphocytes of normal children, newborns, and children with immune deficiency.

The reproducibility of a simplified, sensitive and rapid agarose-cell droplet assay for leucocyte migration inhibition factor (LIF) activity was studied. Removal of T cells with anti-T-cell serum eliminated LIF activity, indicating that in humans it is probably the T cell that produces LIF. Cord blood lymphocytes produce LIF, although spontaneous migration of leucocytes is less than in older children. The cause of this apparently does not reside in the PMN leucocytes. Studies of children with immunodeficiency suggest that the T-cell population in humans is heterogenous. B-cell deficiencies such as hypogammaglobulinaemia, have normal PPD and PHA induced LIF production, whilst some patients with ataxia-telangiectasia have defective PPD LIF activity, their PHA LIF activity being only minimally depressed. On the other hand, Down's syndrome patients with reduced blood T cells have remarkably deficient LIF activity to PHA and relatively good activity to PPD. Children receiving steroid therapy lose much of their ability to produce LIF to the specific antigen PPD, but not to the non-specific mitogen PHA.

Adolescent↗

Measurement of endogenous and TNF alpha-mediated H2O2 production in supernatants of SK-N-SH neuroblastoma cells with an enhanced chemiluminescence assay.

A sensitive peroxidase-dependent luminol-enhanced chemiluminescence (ECL) assay for determination of hydrogen peroxide (H2O2) generation by tumour cells was established. This test system allows determination of H2O2 in concentrations as low as 25 pmol (50 nmol/L) and yields results which are comparable to those obtained using a less sensitive photometric method and a previously described scopoletin fluorescence assay. After 3 h incubation time 10(4) SK-N-SH neuroblastoma cells released 60 +/- 5 pmol H2O2 in the supernatant and this level was significantly (p < 0.025) increased by about 70% in the presence of 5 pmol (100 ng/mL) recombinant tumour necrosis factor alpha (TNF alpha). In contrast, H2O2 production was slightly reduced by TNF alpha at a very low concentration of 0.5 fmol (0.01 ng/mL).

Cell Line↗