Tissue-specific transcription pattern of the adenine nucleotide translocase isoforms in humans.

Three adenine nucleotide translocase isoforms (ANT1, ANT2 and ANT3) are coded by different genes. The relative amounts of the three ANT isoform mRNAs were determined in detail in various human tissues. ANT isoforms were co-expressed in all tested tissues revealing tissue-specific transcription patterns.

Adenine nucleotide translocator in dilated cardiomyopathy: pathophysiological alterations in expression and function.

Several findings pointed to an insufficient energy supply in heart muscle tissue of patients suffering from dilated cardiomyopathy (DCM). We found a lowered ANT transport capacity of the adenine nucleotide translocator (ANT), the only transport system for ATP and ADP in eucaryotic cells, in explanted hearts of DCM patients. The reduced ANT transport rate was accompanied by a marked elevation in total ANT protein caused by an increase in ANT 1 isoform protein.

Autocrine interleukin-1 receptor antagonist can support malignant growth of glioblastoma by blocking growth-inhibiting autocrine loop of interleukin-1.

In situ hybridization (ISH) of human glioblastoma tissue sections revealed expression of interleukin-1 (IL-1)alpha and/or beta and IL-1 receptor types I and II (IL-1R I and II) in the majority of cases evaluable. To understand the function of IL-1-family members in human glioblastomas, we have studied 6 glioblastoma cell lines. RT-PCR, ISH, ELISA and 125I-IL-1-binding assays revealed expression of IL-1 and high-affinity receptors for human (h)IL-1 in all but 1 cell line.

Effects of selenium and iodine deficiency on thyroid hormone concentrations in the central nervous system of the rat.

Objective: The effects of single and combined nutritional selenium and iodine deficiency on intracellular thyroid hormone concentrations and type II 5'-iodothyronine deiodinase (5'D-II) activity were examined in different regions of the adult rat brain.

Design: Four groups (n = 6) of weanling female Wistar rats proceeding from a breeding line fed a selenium-deficient or a selenium-replete diet for 3 generations, were fed selenium-deficient, iodine-deficient, combined selenium- and iodine-deficient or selenium- and iodine-replete diets for 2 months before they were killed.

Methods: Tissue thyroxine (T4) and tri-iodothyronine (T3) concentrations were determined by highly sensitive RIAs after extraction of the iodothyronines from the tissue samples.

Cell-mediated cytotoxicity in hearts with dilated cardiomyopathy: correlation with interstitial fibrosis and foci of activated T lymphocytes.

Objectives: The purpose of this study was to investigate the expression of perforin and T-cell intracellular antigen-1, two crucial components of lymphocyte-mediated cytotoxicity, in endomyocardial biopsies from patients with idiopathic dilated cardiomyopathy.

Background: Previous reports have demonstrated the presence of myocardial interstitial fibrosis and increased infiltrating lymphocytes in patients with dilated cardiomyopathy. However, the pathogenic significance of these lymphocytic infiltrates remains unclear.

Atherosclerosis, aortic stenosis and sudden onset central diabetes insipidus.

The majority of cases of central diabetes insipidus are still pathogenetically unclear (idiopathic). Atherosclerotic cholesterol emboli might be partly responsible for some of these idiopathic cases. A 54-year-old woman with known aortic valve stenosis and a history of a transitory ischemic attack presented with sudden-onset polyuria and polydipsia of up to eight l/d, which had started acutely with headaches.

Assessment of local brain activation. A simultaneous PET and near-infrared spectroscopy study.

In five healthy human subjects, near-infrared spectroscopy (NIRS) and positron emission tomography (PET) examinations were performed simultaneously. Changes in [oxy-Hb], [deoxy-Hb] and [total-Hb] as measured by NIRS over the left forehead were compared to measurements of cerebral blood flow by PET during rest and during performance of a calculation task and a Stroop task. When a penetration depth of near-infrared light 0.

Modulation of the cytosolic Ca++ concentration by alkylphospho-L-serine analogs: relation to their antiproliferative action.

Antiproliferative alkyllysophospholipid (ALP) analogs produced multiple effects on the cytosolic Ca++ concentration ([Ca++]i) in an immortalized human breast epithelial cell line (H 184). The addition of small concentrations resulted in a short transient [Ca++]i response. With higher concentrations the transient rise was followed by a sustained increase.

Harman-induced changes of extracellular concentrations of neurotransmitters in the nucleus accumbens of rats.

Several beta-carbolines, including harman, induce voluntary ethanol intake in rats. It is not clear yet which mechanisms cause these effects. One possibility is the stimulation of the mesolimbic reward system.

Significance of the adenine nucleotide translocator in the pathogenesis of viral heart disease.

We found recently autoantibodies against the adenine nucleotide translocator (ANT), a carrier in the inner mitochondrial membrane, in sera of patients with myocarditis and dilated cardiomyopathy. To elucidate whether these antibodies are of pathophysiological importance, we investigated the function and expression of the adenine nucleotide translocator (ANT) in the heart muscle tissue of patients suffering from myocarditis and DCM. We found a markedly lowered transport capacity of the translocator accompanied by an elevation in total ANT protein content.

Chemopurging of peripheral blood-derived progenitor cells by alkyl-lysophospholipid and its effect on haematopoietic rescue after high-dose therapy.

One reason for relapse after high-dose tumor therapy with subsequent autologous stem cell transplantation is tumor cell contamination of the graft. Removal of tumor cells from bone marrow grafts by chemopurging with the ether lipid edelfosine has been established as an effective and simple method. When compared with bone marrow derived grafts, progenitor cells from peripheral blood have considerably reduced the haematological recovery times.

The future of computer-assisted investigation of the polysomnogram: sleep microstructure.

Previous attempts at automated analysis of sleep were mainly directed towards imitating the Rechtschaffen and Kales rules (RKR) in order to save scoring time and further objectify the procedure. RKR, however, do not take into consideration the sleep microstructure of REM, stage 2, and SWS. While the microstructure of stage 2 has been analyzed in the past decade, the microstructure of REM and SWS are virtually unknown.

Phenolic and tyrosyl ring iodothyronine deiodination and thyroid hormone concentrations in the human central nervous system.

In the present study we investigated the biochemical properties of in vitro phenolic (5'D) and tyrosyl (5D) ring deiodination and the tissue concentrations of T4, T3, and rT3 in adult human central nervous system (CNS) tissue. All samples were obtained from nontumoral tissue at autopsy (n = 6) or neurosurgical operation (n = 5). Both phenolic and tyrosyl ring deiodinase activities were demonstrable in all samples obtained intraoperatively, whereas only tyrosyl ring deiodination was evident in the tissues obtained postmortem.

The role of sensitized T-cells in myocarditis and dilated cardiomyopathy.

Enteroviruses like coxsackie are known to cause myocarditis both in animals and humans and enteroviral genom was found in endomyocardial biopsies of patients with myocarditis and dilated cardiomyopathy. However, subsequent to the initial viral infection, immune mechanisms seem to play an important role in the pathogenesis of both diseases. Using synthetic peptides, it was possible to identify T-cell epitopes of coxsackie B3 virus and to test their significance in the pathogenesis of myocarditis in the animal model.

Immunohistological evidence for a chronic intramyocardial inflammatory process in dilated cardiomyopathy.

Objective: To determine whether immunohistochemical analysis of cardiac biopsies from patients presenting clinically as dilated cardiomyopathy (DCM) show a chronic inflammatory process.

Design: Comparative case control study.

Setting: Tertiary referral centre.

Impairment of left ventricular function in combined immune deficiency mice after transfer of peripheral blood leukocytes from patients with myocarditis.

Autoimmune mechanisms are suspected to play an important role in the pathogenesis of human myocarditis. In order to evaluate the significance of autoimmune leukocytes for the development of human myocarditis (MC) and subsequent heart failure, we transferred 15 x 10(6) or 50 x 10(6) peripheral blood leukocytes (PBLs) from patients with immunohistologically proven MC and impaired left ventricular function into severe combined immune deficiency (SCID) mice that possess neither B nor T lymphocytes. PBLs from seven patients and five healthy controls were transferred into three SCID mice each by intraperitoneal injection.

Treatment of chronic myocarditis with corticosteroids.

Dilated cardiomyopathy (DCM) continues to be an aetiologically unknown heart muscle disease. Recent clinical and experimental data have suggested a temporal relationship with viral myocarditis. The clinical diagnosis of a chronic myocarditis is unspecific.

Antiproliferative effect of human interleukin-4 in human cancer cell lines: studies on the mechanism.

Interleukin-4 (IL-4) plays an important role in activating the immune system against malignant cells. The human interleukin-4 receptor (hIL-4R) is not only expressed by hematopoietic cells but also on a large number of tissue specimens which include colon, breast and lung carcinomas. In this study we report that rhIL-4 has an antiproliferative effect on 2 out of 3 non-small cell lung carcinoma (NSCLC) cell lines in vitro as measured by human tumor cloning assays (HTCA).

Nerve growth factor stimulates clonal growth of human lung cancer cell lines and a human glioblastoma cell line expressing high-affinity nerve growth factor binding sites involving tyrosine kinase signaling.

The growth of a panel of 22 different human tumor, leukemia, and lymphoma cell lines was examined in a human tumor cloning assay in agar or methylcellulose and a tritiated thymidine uptake assay. The cultures were performed in the absence or presence of increasing concentrations (0.5-500 ng/ml) of nerve growth factor (NGF).