Increased lymphocyte beta-adrenergic receptor density in progressive multiple sclerosis is specific for the CD8+, CD28- suppressor cell.

Beta-adrenergic receptor density on T cells from healthy humans is greatest on suppressor cells (CD8+, CD28-) and the effect of catecholamines, secreted by the sympathetic nervous system, predominates on this subset. The sympathetic skin response, a measure of sympathetic nervous system function, is absent in most patients with chronic progressive multiple sclerosis (MS). We measured beta-adrenergic receptor density on suppressor cells, cytotoxic cells, and monocytes from patients with chronic progressive MS and healthy control subjects. Control receptor density on suppressor cells was 2.8 +/- 0.3 fmol/10(6) cells versus a density of 5.1 +/- 0.7 fmol/10(6) cells for patients. Cytotoxic cell (CD8+, CD28+) receptor density was 1.4 +/- 0.4 fmol/10(6) cells in control subjects and 0.9 +/- 0.3 fmol/10(6) cells in the patients. Monocytes displayed beta-adrenergic receptor densities of 2.6 +/- 0.4 fmol/10(6) cells in normal individuals and 2.7 +/- 0.4 fmol/10(6) cells in the patient group. CD8 lymphocyte beta-adrenergic receptor densities in patients with relapsing-remitting and those with stable MS were not different from control values, yet were significantly less than the values for patients with chronic progressive MS. We find that mononuclear cells from healthy control subjects and patients with chronic progressive MS proliferate in response to 200 units/ml of recombinant human interleukin-2 (IL-2) similarly. However, IL-2 treatment increased beta-adrenergic receptor density on normal mononuclear cells, but failed to increase it on mononuclear cells from patients with chronic progressive MS.(ABSTRACT TRUNCATED AT 250 WORDS)     

Three-dimensional human pattern visual evoked potentials. II. Multiple sclerosis patients.

Pattern visual evoked potentials were obtained from 46 patients with definite relapsing/remitting multiple sclerosis, using both a conventional 5-channel occipital array and a 3-D recording technique consisting of three bipolar derivations approximating the three dimensions of space. These three orthogonal wave forms were displayed as a 3-D Lissajous trajectory for each subject. Two of the 15 patients with completely normal conventional pattern VEPs had abnormalities of the orientation of the B-C curvilinear segment of the 3-D pattern VEPs. Delays in the first major occipital positive component (P100) were evident using both techniques; the correlation between P100 latency and the latency of the corresponding trajectory apex was r = 0.99 (P less than 0.01). Post-chiasmal MRI abnormalities were associated with 3-D VEP orientation abnormalities. Three-dimensional pattern VEPs are moderately more sensitive than conventional pattern VEPs at detecting dysfunction posterior to the optic chiasm in demyelinating disease and do not require the use of eccentric fixation to do so.     

Characterization of normal and infarcted rat myocardium using a combination of small-animal PET and clinical MRI.

The combination of small-animal PET and MRI data provides quantitative in vivo insights into cardiac pathophysiology, integrating information on biology and morphology. We sought to determine the feasibility of PET and MRI for the quantification of ischemic injury in the rat model. METHODS: Fourteen healthy male Wistar rats were studied with 18F-FDG PET and cine MRI. Myocardial viability was determined in a transmural myocardial infarction model in 12 additional rats, using 18F-FDG PET and delayed-enhancement MRI with gadolinium-diethylenetriaminepentaacetic acid. All PET was acquired with a dedicated small-animal PET system. MRI was performed on a 1.5-T clinical tomograph with a dedicated small-animal electrocardiographic triggering device and a small surface coil. RESULTS: In normal rats, 18F-FDG uptake was homogeneous throughout the left ventricle. The lowest mean uptake of the 18F-FDG was found in the apical regions (79% +/- 6.0% of maximum) and the highest uptake was in the anterior wall (93% +/- 4.3 % of maximum). Myocardial infarct size as determined by histology correlated well with defects of glucose metabolism obtained with 18F-FDG PET (r = 0.89) and also with delayed-enhancement MRI (r = 0.91). Left ventricular ejection fraction in normal rats measured by cine MRI was 57% +/- 5.4% and decreased to 38% +/- 12.9% (P < 0.001) in the myocardial infarction model. CONCLUSION: Integrating information from small-animal PET and clinical MRI instrumentation allows for the quantitative assessment of cardiac function and infarct size in the rat model. The MRI measurements of scar can be complemented by metabolic imaging, addressing the extent and severity of ischemic injury and providing endpoints for therapeutic interventions.     

Kreatinverluste und Kreatinaufnahme durch isolierte Herzen bei Durchströmung mit kreatinhaltigen Lösungen

Zusammenfassung Mit Krebs-Ringerlösung durchströmte Rattenherzen geben um so weniger Kreatin an die Durchströmungsflüssigkeit ab, je schonender sie präpariert wurden.Nach Zugabe von 3 mg bzw. 5 mg Kreatin zu 100 ml Durchstrom nahmen die meisten Herzen innerhalb von 30 min 400 bzw. 830 Kreatin/g Trockengewicht auf. Weitere Steigerung des Kreatinangebotes verbesserte die Kreatinaufnahme nicht, ebensowenig wie Zugabe von Glucose. Enthielt der Durchstrom Insulin, so wurde die Kreatinaufnahme signifikant erhöht.Die Mehrzahl der mit Kreatin durchströmten Herzen nahm aus der Krebs-Ringerlösung Phosphat auf.Kalium wurde von einigen Herzen abgegeben, von anderen aufgenommen. Die Kaliumaufnahme aus dem Durchstrom war bei geschädigten Herzen am größten. Zusammenhänge zwischen dem Verhalten von Kalium einerseits und Kreatin oder Phosphat andererseits wurden in den Versuchen an isolierten Herzen nicht erkennbar.

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Summary Rat hearts perfused with Krebs' Ringer solution, yielded creatine in the perfusion fluid; the more carefully the hearts were dissected, the smaller was the yield.When creatine was added to the perfusion fluid in concentrations of 3 or 5 mg-%, the hearts took up creatine in most cases to the extent of 400g or 830µg respectively, per g dry weight. A further increase in the creatine concentration did not improve the creatine uptake, nor did an addition of glucose to the perfusion fluid. When the latter contained insulin, the creatine uptake was significantly increased.The majority of the creatine-perfused hearts took up phosphate from the Krebs' Ringer solution.During perfusion some of the hearts yielded potassium, others took up potassium. The potassium uptake was greatest with hearts which had been damaged during the dissection. No connection could be observed in the experiments with isolated hearts between the behaviour of potassium on the one hand, and that of creatine or phosphate on the other.

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Ausgeführt mit Unterstützung des Landes Nordrhein-Westfalen (Landesamt für Forschung).

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Herrn Prof. Dr.E. Lehnartz zum 65. Geburtstag.     

Age-related changes in mechanisms accounting for low levels of polyclonally induced immunoglobulin secretion in humans

The mechanisms accounting for low levels of T-cell-dependent polyclonal IgG secretion in old and young human adults were compared. In elderly donors, in contrast to young donors, low levels of IgG secretion by unfractionated mononuclear cells (MNCs) did not correlate with functional suppressor activity of "panning"-enriched T8+ cells. Levels of IgG secretion by MNCs did not correlate either with proportions of T8+ or T4+ cells in the MNC population or with the functional helper activity of panning-enriched T4+ cells, in either old or young age groups. In young donors suppression mediated by either 2 or 5 X 10(4)T8+ cells of "low" IgG secretors (80.2 +/- 4.8 and 90.2 +/- 1.9%) was significantly greater than that induced by T8+ cells of "high" secretors (41.8 +/- 5.7 and 71.0 +/- 4.0%). Among elderly donors, suppression mediated by either 2 or 5 X 10(4)T8+ cells was reduced in both the low IgG secretion (31.9 +/- 5.3 and 52.3 +/- 7.0%) and high IgG secreting (14.9 +/- 7.2 and 46.8 +/- 5.7%) compared to the corresponding young donor subgroup. Levels of suppression mediated by 2 X 10(4)T8+ cells were suggestively lower in the high IgG secreting elderly subgroup compared to the low secreting subgroup (P less than 0.1). Our data suggest that decreased suppressor activity is a generalized occurrence in aging and that low polyclonal T-dependent MNC IgG secretion in the elderly, in contrast to young adults, cannot be attributed to high T-suppressor activity; nor does it usually reflect defective T-helper activity.     

Avoiding deceptive imprinting of the immune response to HIV-1 infection in vaccine development

Lymphocyte clonal restriction is caused by priming the immune system with an antigen and has been referred to infectious disease study as "original antigenic sin" (OAS), described first for influenza by Francis. OAS is a dominant feature of a normal immune response. Benefits of OAS come from the initial contact with the pathogen, which induces immunological memory. Memory is achieved by priming B and T cells of an immunologically na?ve host, and confers protection against infection with the antigen-related pathogen. Thus, a restricted antibody response to viral or parasite antigens is not per se pathogenic. However, the interplay between a "locked-in" immune response and the high genetic variation of the pathogenic agent can result in a deception of the immune system. In the following, clonal restriction of the immune response to HIV is described by giving examples of restricted anti-HIV antibody formation in maternally infected children. Clonal restriction results in host resistance of infected individuals to emerging HIV variants and quasispecies. The problems of classical approaches of vaccine design in AIDS and the lack of protection in vaccinated patients is reviewed.     

Management of lower urinary tract fibroepithelial polyps in children

IntroductionFibroepithelial polyps (FEP) of the lower urinary tract are relatively common in adults but rare in children, with fewer than 250 cases reported in the literature to date.ObjectiveThe aim of this study was to address the experience of FEP management in children.Study designA retrospective multicenter review was undertaken in children with defined FEP of the lower urinary tract managed between 2008 and 2018. The data at 18 pediatric surgery centers were collected. Their demographic, radiological, surgical, and pathological information were reviewed.ResultsA total of 33 children (26 boys; 7 girls) were treated for FEP of the lower urinary tract at 13 centers. The most common presentation was urinary outflow as hematuria (41%), acute urinary retention (25%), dysuria (19%), or urinary infections (28%). A prenatal diagnosis was made for three patients with hydronephrosis. Almost all of the children (94%) underwent ultrasound imaging of the urinary tract as the first diagnostic examination, 23 (70%) of them also either had an MRI (15%), cystourethrography (25%), computerized tomography (6%), or cystoscopy (45%). Two of these children (6%) had a biopsy prior to the surgery. The median preoperative delay was 7.52 (range: 1–48) months. Most of the patients were treated endoscopically, although four (12.1%) had open surgery and two (6.1%) had an additional incision for specimen extraction. The median hospital stay was 1.5 (range: 1–10) days. There were no recurrences and no complications after a median follow-up of 13 (range: 1–34) months.DiscussionThe main limitation of our study is the retrospective design, although it is the largest one for this pathology.ConclusionThis series supports sonography as the most suitable diagnosis tool before endoscopy to confirm the diagnosis and to perform the resection for most FEP in children. This report confirms the recognized benign nature in the absence of recurrences.Level of EvidenceLevel V.     

Über das Verhalten von Herzglykosiden in der Niere als Ursache ihrer unterschiedlichen diuretischen Aktivität

Ohne Zusammenfassung