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J Bauer

Publications and source records attributed to J Bauer.

At least 289 records · Page 16Linked to original sources
PubMed1996

Inflammatory mechanisms in Alzheimer's disease.

In recent years many studies have indicated an involvement of inflammatory mechanisms in Alzheimer's disease (AD). Acute-phase proteins such as alpha 1-antichymotrypsin and c-reactive protein, elements of the complement system, and activated microglial and astroglial cells are consistently found in brains of AD patients. Most importantly, also cytokines such as interleukin-6 (IL-6) have been detected in the cortices of AD patients, indicating a local activation of components of the unspecific inflammatory system. Up to now it has remained unclear whether inflammatory mechanisms represent a primary event or only an unspecific reaction to brain tissue damage. Therefore, we investigated whether IL-6 immunoreactivity could be found in plaques prior to the onset of neuritic changes, or whether the presence of this cytokine is restricted to later stages of plaque pathology. We confirmed our previous observation that IL-6 is detectable in a significant proportion of plaques in the brains of demented patients. In AD patients IL-6 was found in diffuse plaques in a significant higher ratio as would have been expected from a random distribution of IL-6 among all plaque types. This observation suggests that IL-6 may precede neuritic changes, and that immunological mechanism may be involved both in the transformation from diffuse to neuritic plaques in AD and in the development of dementia.

Alzheimer Disease↗
PubMed1996

The role of macrophage subpopulations in autoimmune disease of the central nervous system.

In this review the role of various subpopulations of macrophages in the pathogenesis of experimental autoimmune encephalomyetitis is discussed. Immunohistochemistry with macrophage markers shows that in this disease different populations of macrophages (i.e. perivascular cells, microglia and infiltrating blood-borne macrophages) are present in the central nervous system. These subpopulations partially overlap in some functional activity while other activities seem to be restricted to a distinct subpopulation, indicating that these subpopulations have different roles in the pathogenesis of encephalomyelitis. The studies discussed in this review reveal that immunocytochemical and morphological studies, combined with new techniques such as in situ nick translation and experimental approaches like the use of bone marrow chimeras and macrophage depletion techniques, give valuable information about the types and functions of cells involved in central nervous system inflammation. The review is divided in three parts. In the first part the experimental autoimmune encephalomyelitis model is introduced. The second part gives an overview of the origin, morphology and functions of the various subpopulations. In the third part the role of these subpopulations is discussed in relation to the various stages (i.e. preclinical, clinical and recovery) of the experimental disease.

Animals↗
PubMed1996

[Chronic fatigue syndrome. Definition, diagnostic measures and therapeutic possibilities].

This article reviews the chronic fatigue syndrome (CFS), a disorder whose etiology is unknown. The diagnostic criteria proposed in 1994 by the CDC and the International Chronic Fatigue Syndrome Study Group are introduced. In contrast to widespread belief, there are no laboratory tests available to underpin the diagnosis of CFS; the diagnosis is made solely on the basis of clinical criteria. In the differential diagnosis, the exclusion of other conditions that can cause chronic fatigue, such as neuropsychiatric or sleep disorders, is of critical importance. In this context, the question as to whether CFS is a clinical entity that can be differentiated from psychiatric diagnoses, such as depression, somatoform disorder, or neurasthenia, is discussed. At the moment, there is no specific therapy for CFS. Therefore, therapeutic approaches are limited to symptomatic management of the concomitant sleep disturbances, pain, or psychiatric symptoms, such as depression. Patients may benefit from cognitive behavioral therapy, as this may help then to identify and exclude factors contributing to and maintaining chronic fatigue. An integrated medical and psychological approach should be adopted, with the aim of preventing significant secondary negative results of the illness, such as interpersonal conflicts or chronic disability.

Adaptation, Psychological↗
PubMed1996

Effects of substance P and selected other neuropeptides on the synthesis of interleukin-1 beta and interleukin-6 in human monocytes: a re-examination.

Recent studies have suggested that substance P (SP) and some other neuropeptides are able to induce the synthesis of the proinflammatory cytokines interleukin-1 (IL-1) and interleukin-6 (IL-6) in peripheral blood mononuclear cells. In the present study, we re-examined these findings by using a completely endotoxin-free monocyte cultivation system. We demonstrate that the neuropeptides SP, vasoactive intestinal peptide, substance K. cholecytokinine, alpha-endorphin and beta-endorphin are consistently unable to induce the synthesis of IL-1 and IL-6 in human peripheral blood monocytes. However, low amounts of LPS (1 pg/ml) synergized with SP to induce IL-6 mRNA expression. In contrast to its lack of effect in monocytes, we were able to confirm the ability of SP to induce cytokine synthesis in astrocytic cells. Our results raise questions about previous results claiming a neuropeptide-induced synthesis of proinflammatory cytokines in human monocytes. In conjunction with other studies, we suggest that undetected levels of endotoxin/LPS in the culture medium may have been primarily responsible for results suggesting an inductive effect of neuropeptides on cytokine synthesis in monocytes.

Blotting, Northern↗
PubMed1996

The participation of interleukin-6, a stress-inducible cytokine, in the pathogenesis of Alzheimer's disease.

A loss of synapses in the cortices of demented persons appears to be the primary correlate of Alzheimer's disease (AD). However, it is still unclear how synaptic pathology is connected to other pathological findings such as neurofibrillary and neuritic degeneration or inflammatory markers in AD. Interleukin-6 (IL-6) immunoreactivity has previously been detected in plaques in the brains of AD patients. In addition, elevated IL-6 concentrations have been measured biochemically in the brains of AD patients. Since transgenic mice bearing additional copies of the IL-6 gene under the control of a brain-specific promoter develop a marked cortical pathology including severe alterations of the dendritic arborization of cortical neurons, an IL-6 related inflammatory event could well be connected to the synaptic pathology in AD. In this study, we investigated whether IL-6 immunoreactivity in plaques could already be found prior to the onset of neuritic changes, or whether the presence of this cytokine is restricted to the later stages of plaque formation. While diffuse plaques represent an early stage of plaque formation, primitive and classic plaques (displaying neuritic pathology) are thought to reflect later stages of plaque pathology. Using a silver-staining method, we classified plaque stages in serial sections of paraffin-embedded cortices of clinically diagnosed and histopathologically confirmed AD patients and of control persons with no clinical history of dementia. Adjacent sections were stained with an antibody directed against IL-6. IL-6 was detectable in a significant proportion of plaques, but only in the brains of demented patients. In the AD cases, IL-6 was found in diffuse plaques in a significantly higher ratio as would have been expected from a random distribution of IL-6 among all plaque types. This observation suggests that IL-6 expression may precede neuritic changes and that in AD an immunological mechanism may be involved both in the transformation from diffuse to primitive plaques and in the development of dementia. The reasons for the increased expression of IL-6 in the brains of AD patients are still unknown. Basal IL-6 levels were found to be slightly elevated along normal aging. Based on several studies indicating that IL-6 expression is inducible also by psychological stress, one could speculate whether long-lasting stressful experiences may contribute to the pathological process underlying Alzheimer's disease.

Aged↗
PubMed1996

Epilepsy and prolactin in adults: a clinical review.

Serum levels of prolactin may increase as a consequence of epileptic seizures. The hormone release is caused by the propagation of epileptic activity, usually from the temporal lobe to the hypothalamic-pituitary axis. Due to the intensity of the epileptic afterdischarge, a rise is seen in approximately 60% of complex partial seizures. Prolactin usually fails to rise after psychogenic seizures, therefore, postictal prolactin levels can be used to differentiate between epileptic and psychogenic seizures. However, a subclassification of epileptic seizures by means of prolactin measurement is not possible. In repetitive seizures, prolactin may show a decrease in its postictal release. This is more common in status epilepticus, probably as a result of a diminished propagation of ictal activity during the course of status epilepticus. The influence of chronic epileptic discharges and anticonvulsant medication on prolactin release is moderate.

Adult↗
PubMed1996

Metabolic rate and energy balance in very low birth weight infants during kangaroo holding by their mothers and fathers.

The aim of the study was to compare effects of maternal and paternal kangaroo care on oxygen consumption, carbon dioxide production, energy expenditure, skin and rectal temperatures, heart and respiratory rates, arterial saturation, and behavioral states. Eleven preterm infants with gestational age of 28 to 31 weeks, birth weight of 560 to 1390 gm, and postnatal age of 8 to 48 days were studied before, during, and after maternal and paternal kangaroo care. Skin temperature (lower leg) increased significantly during both maternal (36.2 +/- 0.9 degrees vs 36.9 +/- 1.2 degrees C) and paternal (36.3 +/- 0.9 degrees vs 36.8 +/- 0.9 degrees C) kangaroo care. The other parameter changed neither during maternal nor during paternal kangaroo care. We conclude that both maternal and paternal kangaroo care have no adverse effects on energy expenditure.

Body Temperature↗
PubMed1996

Nicotine and cotinine stimulate secretion of basic fibroblast growth factor and affect expression of matrix metalloproteinases in cultured human smooth muscle cells.

PURPOSE: We have recently shown that nicotine and its metabolite cotinine are mitogenic for smooth muscle cells in vitro. In the present study, we examined the effect of nicotine and cotinine on the production of growth factors and the expression of matrix metallo-proteinases in smooth muscle cells. METHODS: Smooth muscle cells were harvested from human arteries and grown in culture. Subconfluent cultures were incubated for 24 hours in M199 containing 0.1% fetal bovine serum with or without nicotine or cotinine at concentrations ranging from 10(-9) mol/L to 10(-6) mol/L. The supernatants and cell lysates were assayed by enzyme-linked immunosorbent assay for basic fibroblast growth factor (bFGF), tumor necrosis factor alpha (TNF-alpha), platelet-derived growth factor AB (PDGF-AB), and transforming growth factor beta (TGF-beta). Matrix metalloproteinase expression was determined in subconfluent cultures incubated in albumin with or without nicotine or cotinine at 10(-8) mol/L and 10(-7) mol/L for 6, 12, 18, 24 and 36 hours. Northern blot analyses were performed with human cDNA probes for collagenase-1, stromelysin-1, gelatinase A, gelatinase B, and triose phosphate isomerase. Blots were quantified by phosphor-imaging techniques. RESULTS: Both nicotine and cotinine stimulated the production and secretion of bFGF in a dose-dependent manner. PDGF, TNF-alpha, and TGF-beta secretions were not significantly affected by nicotine or cotinine. Collagenase was up-regulated by nicotine at 18 and 24 hours (4.5-fold to 5.8-fold) and by cotinine at 18 hours (from 5.0-fold to 29-fold). Stromelysin-1 was up-regulated by nicotine and cotinine at 12 and 18 hours (1.5-fold to 7.0-fold). Gelatinase A generally peaked at 12 hours and was up-regulated by both agents (2.0-fold to 6.5-fold). CONCLUSION: Nicotine and cotinine enhanced the production of bFGF, a major mitogen for smooth muscle cells, and up-regulated the expression of several matrix metalloproteinases that are critical in cell migration. These data demonstrate mechanisms by which smoking may contribute to the development of intimal hyperplasia, atherosclerosis, and aneurysms.

Animals↗
PubMed1996

Who is that new nurse?

Explore the source record for details and available documents.

Education, Nursing, Baccalaureate↗
PubMed1996

Adenosine A2b receptors mediate an increase in interleukin (IL)-6 mRNA and IL-6 protein synthesis in human astroglioma cells.

The cytokine interleukin (IL)-6 has recently been demonstrated to play a role in the pathology of Alzheimer's disease (AD). The mechanisms leading to increased IL-6 levels in brains of AD patients are still unknown. Because in experimental animals ischemia increases both the levels of cytokines and the extracellular concentrations of adenosine in the brain, we hypothesized that these two phenomena may be functionally connected and that adenosine might increase IL-6 gene expression in the brain. Here we show that the mixed A1 and A2 agonist 5'-(N-ethylcarboxamido) adenosine (NECA) induces an increase in IL-6 mRNA levels and protein synthesis in the human astrocytoma cell line U373 MG. The A1-specific agonists R-phenylisopropyladenosine and cyclopentyladenosine are much less potent, and the A2a-specific agonist CGS-21860 shows only marginal effects. Increased levels of mRNA are already found within 30 min after NECA treatment. The A2a-selective antagonists 8-(3-chlorostyryl) caffeine and KF17837 [(E)-8-(3,4-dimethoxystyryl)-1,3-dipropyl-7-methylxanthine] , which have also some antagonistic properties at A2b receptors, and the nonspecific adenosine antagonist 8-phenyltheophylline were equipotent at inhibiting the NECA-induced increase in IL-6 protein synthesis, whereas the specific A1 antagonist 8-cyclopentyl-1,3 dipropylxanthine is much less potent. The results indicate that adenosine A2b receptors participate in the regulation of the IL-6 gene in astrocytoma cells.

Adenosine↗
PubMed1996

Interleukin-1 beta uses common and distinct signaling pathways for induction of the interleukin-6 and tumor necrosis factor alpha genes in the human astrocytoma cell line U373.

Cytokines are involved in the etiology of different disorders of the CNS. For a better understanding of their pathogenic role, we analyzed signal transduction pathways mediating the interleukin (IL)-1 beta-induced synthesis of IL-6 and tumor necrosis factor alpha (TNF alpha) in the human astrocytoma cell line U373 MG. Both protein kinase C and reactive oxygen intermediates (ROIs) were involved in IL-6 and TNF alpha gene expression by IL-1 beta. In contrast, protein tyrosine kinases were only necessary for expression of the IL-6 gene. Whereas activation of protein kinase A was able to induce expression of the IL-6 gene, it did not induce TNF alpha gene expression and was not involved in IL-1 beta-induced IL-6 and TNF alpha gene expression. Activation of the transcription factor nuclear factor-kappa B by IL-1 beta involved ROIs, whereas the IL-1 beta-induced activation of the transcription factor AP-1 was mediated via protein kinase C. Our findings provide the basis for the development of specific drugs for the treatment of disorders of the CNS in which cytokines play a pathogenic role.

Astrocytoma↗
PubMed1996

Interleukin-1 beta and tumor necrosis factor-alpha induce expression of alpha 1-antichymotrypsin in human astrocytoma cells by activation of nuclear factor-kappa B.

The protease inhibitor alpha 1-antichymotrypsin (ACT) has been suggested to be involved in the etiology of Alzheimer's disease (AD). Increased levels of ACT have been found in serum and brains of AD patients, and ACT has been proposed to regulate beta-amyloid fibril formation in vitro. To gain insight into the regulation of ACT in the brain, we investigated the signal transduction pathways involved in ACT gene expression and protein synthesis in the human astrocytoma cell line U373. This cell line has previously been shown to respond with strong ACT synthesis on stimulation with interleukin-1 beta (IL-1 beta) or tumor necrosis factor-alpha (TNF alpha). Here, we describe that both IL-1 beta and TNF alpha activate the transcription factor nuclear factor-kappa B (NF-kappa B) via production of reactive oxygen intermediates resulting in ACT expression. In addition, we show that neither protein kinase C nor protein kinase A is involved in IL-1 beta- or TNF alpha-induced ACT expression. These results suggest that activation of NF-kappa B may be one possible cause of increased ACT levels in AD and provide a basis for the development of drugs used for the modulation of inflammatory processes occurring in AD.

Astrocytoma↗
PubMed1996

Salvage chemotherapy with mitomycin, vindesine, and cisplatin (MiViP) in recurrent carcinoma of the cervix.

The combination of mitomycin (8 mg/m(2), i.v., day 1), vindesine (3 mg /m(2), i.v., days 1 and 8), and cisplatin (60 mg/m(2), i.v., day 1) (MiViP) was evaluated in 12 patients with recurrent carcinoma of the cervix. The number of treatment courses ranged from two to eight, with a median of five. Three patients achieved complete remission and six patients showed partial remission, giving and overall response rate of 75%. The median survival was 18 months, with 22 months for responding patients, and 5 months for nonresponding patients (p < 0.01). The major toxicity was myelosuppression. We conclude that MiViP can effectively be used in recurrent carcinoma of the cervix.

Adult↗
PubMed1996

Inhaled nitric oxide in neonatal and pediatric acute respiratory distress syndrome: dose response, prolonged inhalation, and weaning.

OBJECTIVE: Inhaled nitric oxide is a potent and selective pulmonary artery vasodilator. We studied the effects of nitric oxide inhalation in neonatal and pediatric acute respiratory distress syndrome (ARDS) patients with respect to dosage, prolonged inhalation, and weaning. DESIGN: Prospective, open-label study. SETTING: Neonatal and pediatric intensive care units of a level three university hospital. PATIENTS: Seventeen patients with severe ARDS (1 day to 6 yrs of age [mean 1.75]; oxygenation index of > 20 cm H2O/torr) were enrolled. INTERVENTIONS: To identify the optimal dosage for continuous nitric oxide inhalation, doses between 1 and 80 parts per million (ppm) of nitric oxide were tested after the patients had stabilized. Daily withdrawals of nitric oxide were made, according to predetermined criteria. MEASUREMENTS AND MAIN RESULTS: Nine neonatal and eight pediatric ARDS patients (mean Pediatric Risk of Mortality score 28.4 +/- 6.1; mortality risk 54 +/- 15%) were studied. The following variables changed within 24 hrs of nitric oxide inhalation: mean oxygenation index decreased by 56% (from 34 +/- 12 to 15 +/- 7 cm H2O/torr, p = .0004); alveolar-arterial O2 gradient decreased by 31% (from 579 +/- 71 to 399 +/- 102 torr (77.2 +/- 9.5 to 53.2 +/- 13.6 kPa), p = .0004); and mean systemic arterial pressure increased by 15% (from 49 +/- 10 to 57 +/- 12 mm Hg, p = .0029). The optimal dose of nitric oxide was 20 ppm in neonates (with additional persistent pulmonary hypertension of the newborn) and 10 ppm in pediatric patients. Prolonged inhalation (4 to 21 days) was associated with continuous improvement of oxygenation. An oxygenation index of < 5 cm H2O/torr predicted successful withdrawal, with a sensitivity of 75% and a specificity of 89%. None of the patients had to be rescued with extracorporeal membrane oxygenation and 16 of the 17 patients survived. CONCLUSIONS: Inhaled nitric oxide enhances pulmonary gas exchange, with concomitant hemodynamic stabilization, in neonatal and pediatric ARDS. Best effective doses were 10 ppm of nitric oxide in pediatric ARDS and 20 ppm in neonates. Treatment should be continued until an oxygenation index of < or = 5 cm H2O/torr is achieved. Effects on outcome need verification in larger controlled trials.

Administration, Inhalation↗