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Biomedical subjects

J Bauer

Publications and source records attributed to J Bauer.

At least 325 records · Page 18Linked to original sources
PubMed1995

The role of macrophages, perivascular cells, and microglial cells in the pathogenesis of experimental autoimmune encephalomyelitis.

Clinical signs of experimental autoimmune encephalomyelitis (EAE) in rats can be suppressed by treatment with liposomes containing dichloromethylene diphosphonate (Cl2MDP liposomes). Here we investigated whether besides the blood-borne macrophages also ED2+ perivascular cells and microglia are affected by this treatment. For this purpose we examined the central nervous system of bone marrow chimeras in which EAE was induced with encephalitogenic T cells. Quantification of cell numbers of various cell types in inflammatory lesions in the spinal cord showed that after treatment with Cl2MDP liposomes more than 95% of the bone marrow derived (I1-69+) macrophages were eliminated. In addition the number of ED2+ perivascular cells were seen to be decreased by 68% as compared to ED2+ cells in control liposome treated animals. However the number of these perivascular cells in Cl2MDP liposome treated animals did not differ from the number of perivascular cells in naive animals, indicating that only newly recruited, inflammation associated, ED2+ macrophages were eliminated. Moreover, detection of degenerating nuclei by in situ nick translation (ISNT) in combination with staining for ED1 or ED2 showed that in the perivascular space no degenerating cells were present. Cl2MDP liposome treatment furthermore decreased the numbers of T cells infiltrating the parenchyma by more than 50%. Instead T cells were found in large numbers in the perivascular space. Microglia did not seem to be eliminated by Cl2MDP liposome treatment as shown by the absence of ED1+/ISNT+ cells in the CNS parenchyma. However the number of ED1+ (I1-69-) microglial cells decreased by more than 80%, indicating that the activation of this cell type was impaired. It is concluded that bone marrow derived macrophages play an important role in the pathogenesis of EAE via interactions with lymphocytes and the activation of resident microglia.

Animals↗
PubMed1995

Complement C1q and C3 mRNA expression in the frontal cortex of Alzheimer's patients.

The levels and cellular localization of mRNA for complement C1q and C3 were examined by RNA gel blot and nonradioactive in situ hybridization in the frontal cortex of patients with Alzheimer's disease (AD) and age-matched controls. We found that the hybridization signal for C1q mRNA was markedly increased (approx. 3.5-fold) in the frontal cortex of AD patients compared to that in age-matched controls. In contrast to previous reports we also found that the levels of C3 mRNA, although well expressed, did not differ significantly between AD cases and age-matched controls. Nonradioactive in situ hybridization using digoxigenin-labeled ribo-probes revealed that transcripts coding for both C1q and C3 were closely associated with neurons. These results support the hypothesis that complement could play a role in neuronal degeneration which has been observed in the brain of AD patients.

Aged↗
PubMed1995

Interleukin-6 is present in early stages of plaque formation and is restricted to the brains of Alzheimer's disease patients.

Interleukin-6 (IL-6) immunoreactivity has previously been shown in plaques in Alzheimer's disease (AD) and elevated IL-6 concentrations have been measured biochemically in brains of AD patients. In this study, we investigated the appearance of IL-6 immunoreactivity in AD plaques according to the stage of plaque formation. Using the Bielschowsky silver-staining method, we were able to differentiate between four types of plaques described earlier: diffuse, primitive, classic and compact. While diffuse plaques represent the early stage of plaque formation, primitive and classic plaques are thought to represent later stages of plaque development. We investigated serial sections of paraffin-embedded cortices of ten clinically diagnosed and histopathologically confirmed AD patients and ten patients with no clinical history of dementia. We found plaques in the brains of both nondemented and demented persons using the silver staining method or immunohistochemistry with antibodies against the amyloid precursor protein. In the group of clinically nondemented persons, diffuse plaques were the predominant plaque type, whereas primitive plaques formed the larger portion of lesions in the group of AD brains. IL-6 could not be detected in plaques of patients without dementia. Many IL-6-positive plaques were found in six of the AD brains and to a smaller extent in the other four AD cases. In the six cases with a large number of IL-6-positive plaques, IL-6 was found in a significantly higher ratio of diffuse plaques than expected from a random distribution of IL-6 in all plaque types.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

[Determination of Escherichia coli Shiga-like toxins by means of the MTT bioassay].

Tissue culture cells' metabolism and viability are measured by the mitochondrial reduction rate of a yellow tetrazolium salt (MTT) to blue formazan crystals in the MTT-bioassay. Thus the MTT-bioassay is a standardizable and reproducible bioassay for measuring cytotoxicity or cytostimulation. It is shown that the MTT-bioassay is also very suitable for determining bacterial cytotoxins using Escherichia coli's Shiga-like toxins as example. 177 strains of E. coli, isolated from carcasses and organs of cattle, are classified biochemically and tested for cytotoxin production by means of the MTT-bioassay. One of these strains is recognized as producer of Shiga-like toxin 2. 4 Enterohemolysin-producing strains of E. coli are cultivated from a feces sample of a diarrhoeic nubian ibex and identified as Shiga-like toxin 1 producers by help of the MTT-bioassay.

Animals↗
PubMed1995

[Anesthesia for heart transplantation in newborn and suckling infants. Special aspects of the hypoplastic left heart syndrome].

Paediatric cardiac transplantation (pHTX) has gained widespread acceptance as a therapy in end-stage myocardial failure and some forms of congenital heart disease, particularly hypoplastic left heart syndrome (HLHS). The major problems to the anaesthesiologist in these patients are induction of anaesthesia in infants with HLHS and treatment of pulmonary hypertension in the early post-bypass period. PATIENTS AND METHODS. Anaesthesia for pHTX was performed in 15 children < 1 year of age (4-237 days); 12 suffered from HLHS, 2 from endocardial fibroelastosis, and 1 from dilatative cardiomyopathy. Induction of anaesthesia in patients with HLHS IS a challenge to the anaesthesiologist, as he has to maintain the delicate balance between pulmonary and systemic blood flow. Anaesthesia was induced with fentanyl (10-15 micrograms/kg) and pancuronium (0.2-0.4 mg/kg) and maintained with fentanyl (total dosage 70-100 micrograms/kg). Modification of ventilatory parameters such as FiO2, PaCO2, and airway pressure (PEEP, I:E ratio) was used to influence systemic and pulmonary blood distribution in the pre-bypass period according to changes in haemodynamics (target: O2 saturation approximately 75%-80%, PaCO2 45-50 mmHg). Treatment of pulmonary hypertension in the weaning and early post-bypass period consisted of respiratory (PaCO2 < 30 mmHg) and metabolic alkalinisation (pH 7.45-7.55, BE > +3 mmol/l), the use of prostaglandin E1 (3-6-12 micrograms/kg.h), and the phosphodiesterase inhibitor enoximone (10-15 micrograms/kg.min). Additional positive inotropic support was achieved with dobutamine (5-10 micrograms/kg.min), adrenaline (0.1-0.5 micrograms/kg.min), and/or orciprenaline (0.1-0.2 micrograms/kg.min) and calcium chloride (25-100 mg/kg). RESULTS. Two children died intraoperatively and 1 on the 1st postoperative day from overwhelming pulmonary vascular resistance and right ventricular failure. Three children died between 3 and 4 weeks postoperatively, 1 from cytomegalovirus infection, 1 from sepsis, and 1 from acute rejection. Nine patients survived and are well up to 5.5 years after transplantation. CONCLUSION. Pulmonary hypertension in the weaning and early post-bypass period is the main anaesthesiological problem of pHTX, particularly in children with HLHS. A polypragmatic approach to this problem consisting of alkalinisation, pulmonary vasodilatation, and inotropic support is presented and seems to be effective. Further improvements in concepts of pHTX are limited by the lack of donor organs. Though the experience with pHTX in neonates and infants is growing slowly, it might be a routine procedure from the anaesthesiological point of view within a few years in some selected centres.

Anesthesia↗
PubMed1995

A dynamic relationship between myopia and blur-driven accommodation in school-aged children.

Previously we reported that recently myopic children accommodated insufficiently to blur induced by negative lenses. The purpose of the present study was to relate changes in blur-driven accommodation to myopia development in children. Refractive errors and the accommodation response function (ARF) were measured in 23 myopic and 40 emmetropic children on two occasions separated by periods ranging from 6 to 12 months. Repeated measures of accommodation were made with a Canon R-1 autorefractor while negative lenses of increasing power were placed in front of the child's right eye viewing 20/100 letters at 4 m. Concomitant changes in refractive error and in accommodative function over periods of 6-12 months were found to be highly correlated in myopes (r = 0.77) but not in emmetropes (r = 0.09).

Accommodation, Ocular↗
PubMed1995

Reactive oxygen species are involved in the pathogenesis of experimental allergic encephalomyelitis in Lewis rats.

During experimental allergic encephalomyelitis (EAE), both blood-borne macrophages as well as activated, resident microglial cells are considered to be involved in inflammatory reactions in the central nervous system (CNS), resulting in the neurological deficits common to EAE. Both cell types can produce multiple mediators of tissue damage, among which are the reactive oxygen species (ROS). In this study we show that macrophages and microglial cells, isolated from the CNS of Lewis rats with clinical signs of EAE, exhibited significantly elevated spontaneous and phorbol myristate acetate (PMA)-inducible levels of ROS compared to similar cells isolated from healthy controls, sham (complete Freund's adjuvant, CFA)-immunized rats as well as rats sacrificed before the manifestation of clinical signs of EAE. However, during clinical EAE, peripheral blood mononuclear cells (PBMC) did not show increased spontaneous nor PMA-inducible ROS production compared to controls. In vivo treatment of EAE with catalase, which scavenges the ROS H2O2, markedly suppressed the severity of the disease as compared to sham (albumin)-treated controls. In contrast, superoxide dismutase had no effect on clinical signs. Our studies point at a putative functional role for ROS, and in particular H2O2, in the pathogenesis of EAE.

Animals↗
PubMed1995

Endotoxin-induced appearance of immunoreactive interleukin-1 beta in ramified microglia in rat brain: a light and electron microscopic study.

Interleukin-1 plays an important role as mediator of endotoxin-induced responses in the brain such as fever, sleep, anorexia, behavioural and neuroendocrine changes. In the present study, interleukin-1 beta immunocytochemistry has been performed at the light and electron microscopic level to study the cellular and subcellular localization of interleukin-1 beta in the brains of rats given endotoxin or saline. Light microscopic analysis of rats killed 4, 8 or 24h after endotoxin (2.5 mg/kg) given intraperitoneally or intravenously revealed a region-specific localization of immunoreactive interleukin-1 beta in macrophages and microglial cells. After saline treatment, no induction of interleukin-1 beta immunoreactivity occurred in the brain. After administration of endotoxin, many interleukin-1 beta-positive cells were found in the meninges, choroid plexus, circumventricular organs, cerebral cortex and hypothalamus. The number of interleukin-1 beta-positive microglial cells reached a maximum 8 h after administration of endotoxin, irrespective of the route of administration. In general, more interleukin-1 beta-positive microglial cells were found after intravenous than after intraperitoneal administration of endotoxin. Interleukin-1 beta-positive microglial cells were often grouped in patches in the vicinity of blood vessels. At the surface of the cerebral cortex, in the meninges, intermediate cell forms between interleukin-1 beta-positive macrophages and microglial cells were found. interleukin-1 beta-positive perivascular microglia were localized at the brain side of the basal lamina. Immunoreactive interleukin-1 beta was found at the luminal side of the endothelial cells lining the venules. Furthermore, microglial cells that extended their processes into the ependymal layer of the third ventricle were observed. Results of the electron microscopic studies revealed immunoreactive interleukin-1 beta in many cells with the cellular characteristics of microglial cells, but also, in some cells, identified as astrocytes. In microglial cells, immunoreactive interleukin-1 beta was found in the cytoplasm but not in the endoplasmatic reticulum or Golgi apparatus. These results show that after peripheral administration of endotoxin, immunoreactive interleukin-1 beta is induced in macrophages in the meninges and in the choroid plexus, as well as in microglial cells in parenchyma. Interleukin-1 beta produced by these cells may serve as a signal for adjacent or more distant targets (neurons, endothelial cells, microglial cells) to play a role in the induction of non-specific symptoms of sickness.

Animals↗
PubMed1995

Apoptosis in brain-specific autoimmune disease.

Recent neuropathological studies of experimental autoimmune encephalomyelitis have focused attention on the high number of cells in the lesions that show typical morphological features of apoptosis. Surprisingly, it has turned out that the vast majority of apoptotic cells are T lymphocytes and that they actually represent the antigen-specific T-cell population responsible for the induction of the disease. Taken together, these data suggest that clearance of autoimmune inflammation in the nervous system is accomplished by the destruction of the antigen-specific T-cell population within the lesions. This may explain the low level of central nervous system specific T-cell memory formation, as well as previously unexplained phenomena of 'epitope spreading', in autoimmune inflammation of the nervous system.

Animals↗
PubMed1995

Comparison of transthecal digital block and traditional digital block for anesthesia of the finger.

STUDY OBJECTIVE: To compare the newly described transthecal (TT) and traditional (TD) methods of digital block anesthesia with regard to length of time to achieve anesthesia and pain during infiltration. DESIGN: Prospective, randomized, controlled, blinded study. PARTICIPANTS: Healthy adult paid volunteers. INTERVENTIONS: Each subject received a TT block on one hand and a TD block on the opposite hand. All blocks were performed by the same investigator and were rated by an evaluator who was blinded to the technique that was used. Time to loss of pin-prick sensation was measured, and the pain of the procedure was recorded by the subject on a 10-cm visual-analog scale. RESULTS: A total of 162 blocks (81 TT and 81 TD) were performed in 31 different subjects. All blocks were successful. Mean time to anesthesia for TT block was 188 seconds compared with 152 seconds for the TD block (P < .01). Mean analog pain score was slightly higher for TT block than for TD block (1.7 versus 1.4, P = .02). CONCLUSION: TT block is clinically equal to the TD method in terms of time to anesthesia and visual-analog pain score.

Adolescent↗
PubMed1995

Volume estimation of multicellular colon carcinoma spheroids using Cavalieri's principle.

Multicellular tumour-spheroids are regarded as suitable models for cancer research, similar to avascular tumour parts. As a size parameter of the spheroids, usually their maximum diameter is used, estimated on a section presumed to be equatorial or near equatorial. Estimation of the volume of spheroids is of interest for the detection of subtle changes in different kinds of investigations. Since spheroids are often not truly spherical, and because model-based methods for volume determination may be biased, Cavalieri's principle, rediscovered recently for stereology, was used to determine the volume of the spheroids. Here we report the results of the volume estimation of colon carcinoma spheroids, together with an outline of the basic stereological principle and formulas used. The spheroids investigated had a volume between 1.4 and 92.3 mm3 (mean 33.9). The volume fraction of necrotic to viable tissue cells was between 0.6:1 and 2.2:1. The coefficient of error (CE) was remarkably low with 3.7% for the volumes. Both inter- and intraobserver-variability were extremely low with correlation coefficients (r2) of 99%. Thus, the high precision of the stereological method, combined with a low workload, make it ideally suitable for routine volume estimation.

Carcinoma↗
PubMed1995

Intensification of chemotherapy for the treatment of solid tumours: feasibility of a 3-fold increase in dose intensity with peripheral blood progenitor cells and granulocyte colony-stimulating factor.

Dose intensity may be an important determinant of the outcome in cancer chemotherapy, but is often limited by cumulative haematological toxicity. The availability of haematopoietic growth factors such as granulocyte colony-stimulating factor (G-CSF) and of peripheral blood progenitor cell (PBPC) transplantation has allowed the development of a new treatment strategy in which several courses of high-dose combination chemotherapy are administered for the treatment of solid tumours. PBPCs were mobilised before chemotherapy using 12 or 30 micrograms kg-1 day-1 G-CSF (Filgrastim) for 10 days, and were collected by 2-5 leucaphereses. The yields of mononuclear cells, colony-forming units and CD34-positive cells were similar at the two dose levels of Filgrastim, and the numbers of PBPCs were sufficient for rescue following multiple cycles of chemotherapy. High-dose chemotherapy (cyclophosphamide 2.5 g m-2 for 2 days, etoposide 300 mg m-2 for 3 days and cisplatin 50 mg m-2 for 3 days) was administered sequentially for a median of three cycles (range 1-4) to ten patients. Following the 30 evaluable cycles, the median duration of leucopenia < or = 0.5 x 10(9) l-1 and < or = 1.0 x 10(9) l-1 was 7 and 8 days respectively. The median time of thrombopenia < or = 20 x 10(9) l-1 was 6 days. There was no cumulative haematological toxicity. The duration of leucopenia, but not of thrombopenia, was inversely related to the number of reinfused CFU-GM (granulocyte-macrophage colony-forming units). In the majority of patients, neurotoxicity and ototoxicity became dose limiting after three cycles of therapy. However, the average dose intensity delivered was about three times higher than in a standard regimen. The complete response rate in patients with small-cell lung cancers was 66% (95% CI 30-92%) and the median progression-free survival and overall survival were 13 months and 17 months respectively. These results are encouraging and should be compared, in a randomised fashion, with standard dose chemotherapy.

Adult↗
PubMed1995

Pentylenetetrazole-induced seizure up-regulates levels of microtubule-associated protein 1B mRNA and protein in the hippocampus of the rat.

Stimuli that evoke seizure are capable of inducing structural changes in the hippocampus. However, late-acting genes related to these changes have not been described. Administration of pentylenetetrazole (PTZ; 50 mg/kg) to rats of various ages evoked tonic-clonic seizures. Using RNA gel blot analysis we found that the level of the mRNA for microtubule-associated protein 1B (MAP1B) was robustly increased in the hippocampus of 3-month-old rats. The levels of MAP1B mRNA in hippocampus peaked at 40 h and began to decline by 72 h following PTZ treatment. Immunoblotting with anti-MAP1B antibody demonstrates the increase in content of immunoreactive proteins 40-72 h after seizure onset in the hippocampus of PTZ-treated rats. These results indicate that MAP1B is a sensitive indicator of hippocampal structural changes occurring in response to PTZ-induced seizure activity.

Animals↗
PubMed1995

Human follicular and papillary thyroid carcinoma cells interact differently with human venous endothelial cells.

Follicular thyroid carcinomas (FTC) characteristically spread via blood vessels, while papillary thyroid carcinomas (PTC) predominantly metastasize to lymph nodes. This different behavior of cancer cells originating from one organ was investigated by layering multicellular tumor spheroids (MCTS) consisting of various kinds of human thyroid cells onto confluent monolayers of human venous endothelial cells (HEC). The MCTS and HEC were cocultured in an incubation chamber fixed under a microscope, and the behavior of the cells was investigated. In this way significant differences between FTC, PTC, and follicular adenoma cells (FTA) were observed regarding their in vitro behavior upon interaction with HEC. FTC cells required 20 min for adhesion and another hour until they migrated out of a spheroid, whereas PTC- and FTA-MCTS were adhesive after 2 h or later, and their cells did not start migration until 5 h of incubation. Furthermore, one FTC-spheroid triggered about 100 endothelial cells to enter the replication cycle, while no spheroid consisting of either PTC or FTA cells induced more than 20 endothelial cells to start proliferation. During these processes, the cells of the MCTS and the endothelial cells contacted each other directly and remained viable. The results show that FTC cells interact faster and more intensively with human endothelial cells than PTC and FTA cells. Thus the study suggests that an enhanced capability of the FTC cells to interact with venous endothelial cells might favor the clinically observed hematogenous spreading of follicular thyroid carcinomas.

Adenocarcinoma, Follicular↗
PubMed1995

Glomerular function and structure in the sodium-replete and sodium-deplete uninephrectomized spontaneously hypertensive rat: effect of blood pressure reduction, glomerular structure, and blood pressure reduction.

To assess the effects of chronic dietary sodium restriction and blood pressure reduction on glomerular function and structure during the pathogenesis of hypertensive renal disease, experiments were conducted in uninephrectomized (UNX) spontaneously hypertensive rats (SHR) using the dihydropyridine calcium antagonist manidipine. Male SHRs underwent UNX at age 10-11 weeks and subsequently were assigned to one of four groups: sodium-replete (0.4%); sodium-replete and a predetermined antihypertensive dose of manidipine (20 mg/kg body weight); sodium-deplete (0.09%); and sodium-deplete and manidipine (20 mg/kg body weight). Twelve weeks later, renal morphologic and functional studies were performed. Sodium restriction had no significant effect on systolic blood pressure, but creatinine clearance and urinary protein excretion were decreased. Importantly, mean glomerular volume and the prevalence of mesangial expansion were lower with sodium restriction. This occurred in the presence of high concentrations of plasma and renal tissue angiotensin II. Manidipine significantly reduced systolic blood pressure in the sodium-replete and sodium-deplete UNX-SHRs. This therapy was not associated with significant changes in creatinine clearance and urinary protein excretion in the sodium-deplete or sodium-replete UNX-SHRs. The prevalence of mesangial expansion in the sodium-replete UNX-SHR was approximately 50% lower with manidipine. Plasma and renal tissue angiotensin II concentrations were not affected by the drug. In the sodium-deplete UNX-SHR, the prevalence of mesangial expansion was not reduced further by manidipine. However, plasma and renal tissue angiotensin II concentrations were increased significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1995

Basic research.

Basic research is currently investigating the molecular cascade associated with bladder cancer development. Many new findings are potential leads towards the improvement of the diagnosis and prognosis of this disease. Special care, however, should be taken in the design of protocols for clinical evaluation of the value of these markers. Some initial guidelines have been put forward in this report.

Alleles↗