PubMed Health⌕ Search

Biomedical subjects

B Sander

Publications and source records attributed to B Sander.

At least 73 records · Page 4Linked to original sources

Early expression of cytokines in lymph nodes after treatment in vivo with Staphylococcus enterotoxin B.

Excessive cytokine expression induced by superantigen may be one aspect of the pathophysiology associated with Gram positive bacteremia. We have undertaken a study of the kinetics of cytokine production in lymph nodes obtained from in vivo Staphylococcus enterotoxin B (SEB) treated animals. This study was designed to evaluate the short term cytokine profile observed using immunohistochemistry (IHC) in BALB/c mice injected intraperitoneally (i.p.). The observed immunohistochemical kinetic profiles were corroborated using reverse transcription-polymerase chain reaction (RT-PCR) RNA analysis. We report here that TNF, IL-2, and IFN-gamma are the principal cytokines which were detected within hours of SEB administration, and that other cytokines such as IL-3, IL-4, IL-5, IL-6, IL-10, GM-CSF and M-CSF were undetectable. TNF and IL-2 appeared very early following SEB priming, and were observed by 1 h. IFN-gamma which appeared later (maximally at 14 h) was produced predominantly by CD8+ cells. In contrast, the TNF and IL-2 were produced primarily by CD4+ cells. Identical results were obtained by IHC and RT-PCR; the kinetics of mRNA expression slightly preceded the appearance of protein. The TNF and IFN-gamma staining patterns observed in lymph node sections were indicative of Golgi-localized cytokine. The IL-2 staining pattern observed in lymph node sections was distinctive, covering a significant local area of cells. This local regional concentration of IL-2, which may result from cytokine attached to extracellular binding components, may be an important aspect of the activation phase of a developing immune response. Rapid induction and excessive cytokine production elicited by superantigen in vivo, may ultimately help to explain the shock and death associated with SEB.

Animals↗

Induction of lactase biosynthesis in the human intestinal epithelial cell line Caco-2.

The human colonic adenocarcinoma cell line Caco-2 forms monolayers of differentiated enterocyte-like cells when cultured on permeable supports. After confluency, Caco-2 cells express a number of brush-border enzymes including lactase-phlorizin hydrolase, sucrase-isomaltase and dipeptidylpeptidase IV. We have studied, with particular emphasis on lactase-phlorizin hydrolase, the modulation of biosynthesis of these enzymes by stimulating second messenger systems. Forskolin induced lactase-phlorizin hydrolase synthesis approximately fourfold within 7 h, suppressed sucrase-isomaltase synthesis, and had little effect on dipeptidylpeptidase IV. Dibutyryl-cAMP, 8-bromo-cAMP and vasoactive intestinal peptide also increased lactase-phlorizin hydrolase biosynthesis, indicating c-AMP dependent regulation. The induction of lactase-phlorizin hydrolase biosynthesis could be inhibited by actinomycin D and was preceded by a fourfold increase in lactase-phlorizin hydrolase mRNA levels, suggesting transcriptional control. Phorbol 12-myristate 13-acetate had an inhibitory effect on brush-border enzyme synthesis, in particular on sucrase-isomaltase, and blocked the forskolin-induced biosynthesis of lactase-phlorizin hydrolase. Lactase-phlorizin hydrolase synthesis was also inducible by hydrocortisone, but maximal induction required at least 3 days during which time sucrase-isomaltase synthesis diminished. The results indicate opposite regulation of lactase-phlorizin hydrolase and sucrase-isomaltase via cAMP and corticosteroids, and suggest that the Caco-2 cell line can serve as a model system to study aspects of the humoral regulation of human intestinal brush-border enzymes in cell culture.

1-Methyl-3-isobutylxanthine↗

HIV-1 inhibits Leishmania-induced cell proliferation but not production of interleukin-6 and tumour necrosis factor alpha.

The immune response of normal human peripheral blood mononuclear cells (PBMC) after stimulation with human immunodeficiency virus-1 (HIV-1) antigens plus Leishmania donovani promastigotes in vitro was investigated. HIV-1-antigen stimulation of PBMC did not induce the intracellular accumulation of interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), or interferon-gamma (IFN-gamma). However, cells stimulated with L. donovani antigens exhibited the production of IL-6 and TNF-alpha, but not IFN-gamma. Furthermore, co-stimulation of PBMC with HIV-1 antigen plus L. donovani resulted in the intracellular accumulation of IL-6 and TNF-alpha comparable to that of cells that were activated with L. donovani antigen alone. Heat-inactivated HIV-1 antigen did not appear to induce or suppress cytokine production by PBMC. However, the same HIV antigens did suppress L. donovani-induced proliferation as well as PPD-induced proliferation in a dose-dependent fashion. Elevated levels of serum cytokines have been demonstrated in patients with HIV infection indicating their role in the pathogenesis of HIV-associated immunosuppression. The results may partially support the idea that the abnormally increased cytokine levels in the sera of HIV-infected subjects is due to the various opportunistic pathogens that these patients contract, rather than a response to HIV antigens. As cytokines have been shown to up-regulate HIV replication, the data suggest a role for opportunistic infections in cytokine-induced transactivation of HIV-1 and disease progression.

AIDS-Related Opportunistic Infections↗

Fluorescein transport across the human blood-retina barrier in the direction vitreous to blood. Quantitative assessment in vivo.

Inward and outward movement of flourescein across the human blood-retina barrier was studied in five healthy volunteers, using a differential spectrofluorometry method that eliminates the contribution of fluorescein glucuronide to the total fluorescence in the vitreous and in plasma. The inward permeability across the blood-retina barrier, which is presumed to be passive, and the diffusion coefficient in the vitreous for fluorescein was calculated from data obtained 1 h after intravenous injection of fluorescein. The rate of elimination of fluorescein from the vitreous across the blood-retina barrier was estimated from data obtained 7 to 12 h after injection of fluorescein. The calculations were based upon the free plasma fluorescein decay curve and the preretinal fluorescein gradient in the vitreous. The mean inward permeability of fluorescein was 1.39 x 10(-7) cm/sec (range: 0.70-2.06 x 10(-7) cm/sec), whereas the mean outward permeability was 1.51 x 10(-5) cm/sec (range: 1.14-1.73 x 10(-5) cm/sec). We have thus found that the movement of fluorescein across the blood-retina barrier is highly asymmetric, the outward transport being more than 100 times faster than the passive inward leakage. This could indicate the presence of an active pumping mechanism in the blood-retina barrier, responsible for fluorescein transport in the direction from the vitreous to the blood.

Biological Transport, Active↗

Probenecid inhibition of the outward transport of fluorescein across the human blood-retina barrier.

The effect of probenecid on the outward transport of fluorescein from vitreous to blood was studied in 13 insulin-dependent diabetic patients with background retinopathy in a randomised double-masked placebo controlled cross-over study. Fluorescein and fluorescein glucuronide was separated in the vitreous and in plasma by differential spectrofluorometry. The data for fluorescein were analysed using a simplified mathematical model of the eye. The inward permeability was estimated from data obtained 1 h after injection and the outward transport from data obtained 7 h after injection. During placebo treatment the mean inward permeability was 3.75 x 10(-7) cm/sec and the mean outward permeability was 2.25 x 10(-5) cm/sec. During probenecid treatment the mean inward permeability was 3.34 x 10(-7) cm/sec and the mean outward permeability was 1.44 x 10(-5) cm/sec. Thus, we found no significant change in inward permeability (p = 0.5879), whereas a significant decrease of 36% was found in the outward permeability of fluorescein (p = 0.0171). The demonstration that the outward permeability, which is more than 100-fold higher than the inward permeability in the healthy eye, is significantly decreased by probenecid, demonstrates that active transport is involved in movement of fluorescein across the blood-retina barrier from the vitreous to the plasma.

Adult↗

Absence of foveal avascular zone demonstrated by laser scanning fluorescein angiography.

We present laser scanning fluorescein angiograms of abnormal foveal capillary patterns in a healthy subject and an insulin-dependent diabetic patient with mild diabetic retinopathy. In both subjects capillaries were seen to cross the central foveal area where capillaries are usually absent. The flow pattern of the foveal capillaries, which were visualised with the use of a laser scanning ophthalmoscope, was indistinguishable from that of the more peripheral capillaries, indicating that foveal vessels are functionally normal retinal capillaries. The two cases demonstrate that identification of abnormal capillary patterns induced by retinal disease such as diabetic retinopathy is made difficult by the marked interindividual variation in capillary anatomy. In prospective studies, however, the method may be capable of detecting subtle changes in early diabetic retinopathy with a high degree of sensitivity.

Adult↗

Early changes in diabetic retinopathy: capillary loss and blood-retina barrier permeability in relation to metabolic control.

In diabetic retinopathy capillary loss and blood-retina barrier leakage are prominent factors. We present a study with quantitative measurements of both capillary loss and leakage and their relation to cumulative metabolic control. Seventeen insulin-dependent diabetic patients with no retinopathy or only mild background retinopathy and 10 years' duration of the disease were included in the study. Status of metabolic regulation had been followed for at least 6 years. Seven healthy subjects were included as controls. In diabetic patients the perifoveal intervascular areas were found to increase significantly with the cumulative HbA1c index (p = 0.02) and in relation to the presence of moderate background retinopathy (p < 0.02). The blood-retina barrier leakage and the area of the foveal avascular zone were not significantly different from healthy subjects and no correlation was found between the HbA1c index and blood-retina barrier permeability. We conclude that perifoveal capillary loss occurs early in the course of diabetic retinopathy and that this loss is related to prior glycemic control and to the ophthalmoscopic retinopathy level.

Adult↗

Interferon alfa-2a modifies the course of subfoveal and juxtafoveal choroidal neovascularisation.

The first double masked placebo controlled trial of interferon alfa-2a for the treatment of overt choroidal neovascular membranes is presented. A total of 43 consecutive patients were randomised to double masked treatment with either interferon alfa-2a, 3 million IU subcutaneously three times a week or matching placebo, for a period of 8 weeks. End of study changes from baseline in distance and near visual acuity, macular visual field, contrast sensitivity, and macular morphology (fluorescein angiography) were assessed. The between group difference in distance visual acuity, the primary efficacy variable, was significant in favour of interferon alfa-2a (p = 0.023). Fluorescein angiograms, macular visual fields, and near vision all showed a trend in favour of interferon alfa-2a. It was concluded that, at the dosage used in this study, interferon alfa-2a is a reasonably well tolerated and apparently effective short term treatment of subfoveal and juxtafoveal choroidal neovascularisations.

Adult↗

[MRT in degenerative diseases of the cervical spine].

MRI has grown increasingly important in recent years in diagnosis of degenerative disease of the cervical spine, due to improvements of method that have made it a valuable diagnostic tool. The following contribution gives a brief introduction to the pathophysiology of degenerative changes in the cervical vertebral column and to the indications for MRI, describing within the framework of imaging the present state of MR examination technique. The ranking of the various gradient echo sequences, of the 3D methods and of the administration of contrast media in cervical myelopathy and radiculopathy is discussed.

Cervical Vertebrae↗

Similar frequencies and kinetics of cytokine producing cells in murine peripheral blood and spleen. Cytokine detection by immunoassay and intracellular immunostaining.

Production of IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, IFN-gamma, GM-CSF (granulocyte-macrophage colony stimulating factor) and macrophage colony stimulating factor by murine peripheral blood and spleen cells was analyzed following primary and secondary mitogen stimulation in vitro. Individual cytokine producing cells were detected by an intracytoplasmic staining technique. Cytokine production in cells from peripheral blood and spleen was comparable and more rapidly induced by calcium ionophore and phorbol 12-myristate 13-acetate than by concanavaling A. Restimulation in vitro induced both a swift production of cytokines and, for some cytokines, higher frequencies of producing cells. This was especially evident for IL-10 secreting cells, which increased 30-80 times in secondary responses. These analyses using the dual approaches of immunoenzymetric and fluorescent immunohistochemical techniques provide important evidence that cytokine induction kinetics can differ following primary or secondary stimulation.

Animals↗

[MRT in cervical disk herniation: plain vs. contrast-enhanced images].

Aim of this study was to assess the value of Gd-DTPA administration in MRI of cervical disk herniations. In 34 patients, showing 40 cervical disk herniations, plain proton density- and T1-weighted as well as contrast-enhanced T1-weighted 2D-FLASH images were generated. Contrast between the herniated material and the CSF already was sufficient without administration of Gd-DTPA in all cases. Sufficient contrast between the herniations and the intraforaminal structures was obtained in 13/40 cases and 40/40 cases on plain and contrast-enhanced images, respectively. Definition of the herniated disks was judged to be sufficient in 30/40 cases on plain images and 40/40 cases on contrast-enhanced images. The diagnostic value of the images was improved in 3/12 lateral and 7/8 intraforaminal herniations by contrast administration, whereas there was no significant increase in diagnostic value in posterior or posterolateral herniations. As a result, Gd-DTPA administration is recommended if definition of lateral and intraforaminal disk herniations in MRI is poor.

Adult↗

[The differential diagnosis of Parkinson diseases--123I-IBZM-SPECT vs. the apomorphine test].

The aim of our study was to compare the striatal dopamine D2-receptor density as measured by 123I-IBZM-SPECT with the results of the apomorphine-test. 30 patients were studied; 21 with idiopathic Parkinson's disease (IPD), 9 with Parkinson plus syndromes (PPS). Patients with IPD showed a significantly higher striatal IBZM binding as compared to patients with PPS (p = 0.006). A good correlation between IBZM binding and outcome of the apomorphine-test was found (p = 0.006). Low striatal IBZM binding indicates reduced dopamine D2-receptor density. This compromises successful dopaminergic medical therapy and is indicative of non-IPD disease. 123I-IBZM-SPECT could be diagnostic aid in the work-up of patients with extrapyramidal movement disorders. The response to dopaminergic drug treatment might be precluded by IBZM-SPECT in patients with Parkinsonian syndromes.

Adult↗

Interferon alpha-2a treatment of patients with subfoveal neovascular macular degeneration. A pilot investigation.

It has recently been suggested that interferon alpha-2a has a beneficial effect on exudative age-related macular degeneration (AMD). So far, results are controversial, and masked, placebo controlled, randomized studies with well-defined inclusion criteria are required to assess the effect of interferon alpha-2a. In preparation for such a study we performed a pilot investigation that included 5 patients with subfoveal neovascularizations. All patients received interferon alpha-2a (Roferon-A, Hoffmann La-Roche) 1.5 mio, IU subcutaneously every second day for 8 weeks. Improved visual acuity was subjectively observed by 4 patients and objectively by 3 patients. Two patients showed decreased central visual field defect. Fluorescein angiography and fundus photography showed ambiguous changes. Amsler chart and contrast sensitivity also showed heterogenous results. Even though the treatment with interferon alpha-2a may show some positive effect, our results are not unequivocal and serve to underline the need for controlled studies before the effect of interferon alpha-2a on neovascular AMD can be reliably assessed.

Adult↗

[Magnetic resonance tomographic characterization of intracranial tumors by evaluating the blood-brain barrier and regional cerebral circulation].

The aim of this prospective study was to characterize intracranial tumors on the basis of the degree of blood-brain-barrier (BBB) disruption and tumor blood flow (TBF). We studied 28 patients with brain tumors by MRI. BBB disruption was demonstrated by a pathological increase of signal intensity in T1-weighted spin-echo images (1.5 T, TR = 600 ms, TE = 10 ms, alpha = 90 degrees) after intravenous gadolinium-DTPA injection. TBF flow was assessed by an MRI-method based on the signal intensity decrease in T2-weighted gradient-echo images (TR = 25 ms, TE = 20 ms, alpha = 10 degrees) immediately after gadolinium-DTPA bolus injection. Typical constellations include intake BBB and low TBF in low-grade intraaxial tumors (astrocytoma I/II), disrupted BBB and heterogeneous TBF in high-grade intraaxial tumors (glioblastomas and metastases), and disrupted BBB and high TBF in extraaxial tumors (meningeomas). This study demonstrates the quasi-simultaneous assessment of the blood-brain-barrier and tumor blood flow. The results support the concept that additional uncorrelated information is obtained from the assessment of regional cerebral blood flow that may be helpful for the differential diagnosis of brain tumors.

Astrocytoma↗

["Surgical projection" in the gadolinium-DTPA (Gd-DTPA)-supported NMR tomographic diagnosis of lateral lumbar disk prolapse].

In a group of 25 patients the coronal views of plain and Gd-DTPA-enhanced MRI studies were correlated with CT and operative findings. All series included sagittal, transverse and coronal FLASH sequences (GE 500/6, flip angle 70 degrees), sagittal proton density-(SE 2500/15) and T2-(SE 2500/70) weighted images. MR diagnosis proved to be correct in all cases. Compared to CT and axial MRI herniated disk material in the lateral intravertebral space and its relationship to nerve roots was demonstrated more clearly on coronal views.

Adult↗

[The regional cerebral circulation in infarct patients. Rapid dynamic T2*-weighted MRT after a bolus injection of gadolinium-DTPA].

The aim was to validate the MRI assessment of regional cerebral blood flow. Measurements were performed on a 1.5 T imaging system using a fast T2*-weighted gradient-echo sequence. After intravenous injection of gadolinium-DTPA 30 images were acquired in the same slice position during 84 seconds. In 12 volunteers we observed a symmetrical cortical decrease of signal intensity during the passage of the contrast medium. In 9/23 patients with impairment of cerebral blood flow a circumscribed area of reduced signal intensity decrease (hypoperfusion) was found. In 4/23 patients the decrease of signal intensity was more pronounced than in normals (hyperfusion). In 9/23 patients signal intensity changes were normal. HMPAO-SPECT confirmed successful MRI assessment of cerebral blood flow in 22/23 patients.

Cerebral Infarction↗

[Magnetic resonance tomographic screening studies of the bone marrow with gradient-echo sequences. II. Gadolinium-DTPA-supported studies of plasmocytoma patients].

MR imaging was performed in 19 patients with proven multiple myeloma. Both plain and Gd-DTPA enhanced in-phase and opposed-phase gradient-echo techniques were used (0.1 mmol Magnevist/kg body weight). Plain, opposed-phase imaging demonstrated more lesions than plain in-phase imaging (35 vs. 16); enhanced opposed-phase imaging demonstrated more lesions than plain opposed-phase and enhanced in-phase imaging (47 vs. 35 and 17 lesions). These results suggest that enhanced opposed-phase images which have a high contrast between normal and infiltrated bone marrow are especially suited for MR screening in multiple myeloma.

Bone Marrow↗