Zur Polypeptidketten-Struktur von Immunglobulinen

Zusammenfassung Individuelle normale IgG wurden isoelektrisch in eine Vielzahl von Komponenten getrennt, deren IP zwischen pH 5,5 und 9,5 lagen. Im Gegensatz dazu focussierten individuelle Myelom IgG einheitlich. Die isoelektrischen Punkte dieser Paraproteine unterschieden sich untereinander stark, verteilten sich alle zusammen jedoch ebenfalls über den pH-Bereich 5–9. Dieser Befund entspricht der Auffassung, daß diese Paraproteine normale Immunglobuline repräsentieren.Ähnliche Ergebnisse hatte die Fraktionierung der L- und H-Polypeptidketten. Während normale L- und H-Ketten eine ausgeprägte Heterogenität aufwiesen, waren die IgG-L- und H-Ketten von Myelomproteinen einheitlich. Mittels gleichzeitiger Anwendung der PAA-Elektrophorese, quantitativen Aminosäurenanalyse, Endgruppenbestimmung und anderer protein-chemischer Methoden konnte gezeigt werden, daß im Falle der L-Ketten sowohl die Aminosäureverteilung als auch die Konfiguration das unterschiedliche isoelektrische Verhalten bedingt. Die Anwendung der isoelektrischen Analyse für den Nachweis von Rekombinatbildungen aus L- und H-Ketten wurde gezeigt.

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Summary Myeloma IgG and its light and heavy polypeptide chains were subjected to isoelectric focusing in a vertical column containing a combined pH and density gradient. The results have been compared to those obtained by isoelectric separation of normal individual IgG and its polypeptide chains. In carrier ampholytes of two pH steps each individual myeloma globulin was focused in only one fraction, but the isoelectric points of all myeloma globulins were distributed between pH 5 and pH 9. In contrast to these results each normal individual IgG was electrofocused in a multiplicity of isoelectric fractions exhibiting the same pH range from pH 5 to pH 9. Similar results were obtained by the analysis of light and heavy polypeptide chains. A remarkable degree of heterogeneity could be demonstrated in normal and a homogenous isoelectric pattern in myeloma IgG polypepide chains. By polyacrylamide-gel-electrophoresis it could be demonstrated that a direct proportionality of isoelectric point and electrophoretic mobility in polyacrylamide-gel did'nt exist. By the quantitative aminoacid determination, endgroup analysis and other physico-chemical methods it could be shown, that differences in the isoelectric point of L-chains are not exclusively caused by differences in the amino acid composition. The use of isoelectric focusing for the analysis of L- and H-chains recombination has been demonstrated.

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Wir danken der Deutschen Forschungsgemeinschaft für ihre Unterstützung.     

Conditioning of dendritic cells by pathogen-derived stimuli

No Abstract     

Epidemiology,characterization, and diagnosis of neuropsychiatric events in systemic lupus erythematosus

Introduction: Neuropsychiatric systemic lupus erythematosus (NPSLE) is characterized by a heterogeneity of clinical manifestations. The absence of diagnostic criteria and the lack of clinical trials is a challenge in clinical practice.

Areas covered: A literature review was performed to describe epidemiology, characterization (clinical, immunological, and imaging), diagnosis and treatment of NPSLE. Classification criteria have been the first step towards a uniform definition. More recently, different attribution models have been developed to help to determine if the NP event is due to SLE. Disease activity is a major risk factor for NP events. Cytokines and autoantibodies are associated with NP events, however, only a few studies have identified risk factors for individual NP events.

Expert opinion: Further research needs to search for and validate biomarkers for NPSLE and individual NP events, including neuroimaging findings, attribution models, and serologic markers. This will be a fundamental step in planning randomized control trials in the treatment of NPSLE to improve outcome.     

Comparative study of complications after primary and revision transsphenoidal endoscopic surgeries

Neurosurgical Review - A preferred treatment for residual/recurrent pituitary adenomas has not been established. The existence of higher complication rates for revision surgeries remains under...     

Donor Choriocarcinoma Transmission From Solid Organ Transplantation: A Case Report

Transplantation of any organ has some inherent risk of disease transmission, such as infection and malignancy. The present study aims to describe 2 cases of choriocarcinoma transmission after kidney and liver transplantation originating from the same patient. The donor was a 17-year-old woman who died of cerebral hemorrhage. Both organ recipients died of metastatic choriocarcinoma few months after the transplantation, within days after starting chemotherapy. Retrospective hCG (human chorionic gonadotropin hormone) analysis in donor's blood stored at the time of donation had a result of 9324 mIU/mL. Despite its rarity, clinicians should be aware of the risk of transplant-related choriocarcinoma from female donors in childbearing age. In some cases, hCG dosage should be performed before donation.     

Novel collagen scaffolds with predefined internal morphology made by solid freeform fabrication

Novel collagen scaffolds possessing predefined and reproducible internal channels with widths of 135 microm and greater have been produced. The process employed to make the collagen scaffold utilises a sacrificial mould, manufactured using solid freeform fabrication technology, and critical point drying technique. A computer aided design (CAD) file of the mould to be produced is created. This mould is manufactured using a phase change ink-jet printer. A dispersion of collagen is then cast into the mould and frozen. The mould is dissolved away with ethanol and the collagen scaffold is then critical point dried with liquid carbon dioxide. The effect of processing on the tertiary structure of collagen is assessed by monitoring the wavenumber of the N-H stretching vibration peak using Fourier transform infra-red spectroscopy and it is found that processing does not denature the collagen. Ultraviolet-visual spectroscopy was used to detect the presence of any contamination from the sacrificial mould on the collagen. The ability to use computer aided design and manufacture (CAD/CAM) provides a route to optimise scaffold designs using collagen in tissue engineering applications.     

Expression of major histocompatibility class II antigens on polymorphonuclear neutrophils in patients with Wegener's granulomatosis

BACKGROUND: Wegener's granulomatosis is a systemic inflammatory disease of unknown etiology. Many studies suggest that autoimmune reactions are involved, and there is good evidence for the participation of immunocompetent cells. In that context, we examined the activation of polymorphonuclear neutrophils (PMNs) of patients with Wegener's granulomatosis. METHODS: In a prospective study, the expression on the surface of PMNs of CD64 and of the major histocompatibility class II (MHC II) antigen was measured by cytofluorometry in whole blood. The expression of those antigens was correlated to disease activity. RESULTS: Up to 15% of the peripheral PMNs of patients with active disease expressed MHC II. Follow-up studies showed that expression correlated closely with disease activity and that it decreased rapidly under immunosuppressive therapy. Expression of CD64 was seen in approximately 50% of the patients, regardless of disease activity. CONCLUSION: MHC II expression on PMNs might serve as a novel diagnostic marker for active disease and appears to be suitable for monitoring immunotherapy. Moreover, our data provide evidence that PMNs, which are normally MHC II negative, acquire MHC II antigens in the course of disease and may be an unrecognized function within the afferent limb of the immune response.     

Psoas muscular abscess in children

Symptoms of psoas muscular abscess in children are nonspecific and differential diagnosis is made among diseases included in childreńs acute hip pain syndrome, imaging tests being necessary for diagnostic confirmation. During the first semester of 1995, 48,550 children were examined in Pronto Socorro do Instituto da Crian?a do Hospital das Clínicas da Faculdade de Medicina da Universidade de S?o Paulo, four of them diagnosed as having psoas muscular abscess (2 females and 2 males, ages varying from 1 to 12 years). All of them had nonspecific clinical features and diagnosis was confirmed by abdominal ultrasound and/or computerized tomography. Staphylococcus aureus was isolated as the etiologic agent in 3 children, findings similar to the ones in literature.     

Time of appearance during development of differences in nigrostriatal tyrosine hydroxylase activity in two inbred mouse strains

The greater activity of tyrosine hydroxylase (TH) in substantia nigra and corpus striata of adult BALB/cJ than CBA/J mice, is attributable to differences in the number of dopamine neurons in the ventral midbrain tegmentum. To determine if strain differences in TH activity develop postnatally we have measured the development of TH in the midbrain (SN) and in the corpus striatum (CS). In the midbrain neonatal TH activity was 20% of adult levels. Thereafter, TH activity increased rapidly achieving adult levels by 11 days. A 25% "overshoot' above adult values at 15 days was followed by a gradual decrease to adult activity at 4 weeks. In the CS neonatal activity was about 10% of adult levels and increased slowly to reach adult values at 4 weeks. Striatal choline acetyltransferase (CAT) activity in the neonate was only 3.7% of adult values and at 21 days had only reached 70% of adult activity. Neonatal glutamic acid decarboxylase (GAD) activity was relatively high in both brain regions and increased gradually to adult activity by 4 weeks. Strain differences in TH activity were not present at birth but first appeared at 9 days in SN and 11 days in CS. Once established, the differences were maintained. These results suggest that strain differences in TH are most probably a consequence of differences in postnatal neuron survival, although the possibility that some neurons lose their phenotypic expression of TH cannot be excluded.