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.     

Effect of prostaglandin E2 and 3-morpholinosydnonimine (SIN-1) on arachidonic acid metabolism in fMLP-stimulated rat neutrophils and on thrombin-induced human platelet aggregation

The effects of prostaglandin (PG) E₂ and the nitric oxide (NO) donor SIN-1 on leukotriene (LT) release from formyl-methionyl-leucyl-phenylalanine (fMLP) (100 nM)-stimulated rat peritoneal neutrophils (RPN) and on thrombin-induced aggregation of washed human platelets were investigated. Both PGE₂ (1–100 nM) and SIN-1 (30–300 M) inhibited release of LTB₄ and cysteinyl-LT from RPN in a concentration-dependent manner. The combined effects of PGE₂ and SIN-1 were not greater than expected by summation. On the other hand, the inhibitory effect of SIN-1 (0.5 or 1.0 M) on platelet aggregation was potentiated by PGE₂ (0.3–5 M) in a concentration-dependent manner, while PGE₂ alone in the concentrations used had only marginal effects. The results suggest differential regulation of platelet and leukocyte functions by the mediators PGE₂ and NO, which could be relevant for various physiological and pathophysiological conditions.     

Endokrin aktive Tumoren des Ovars

Zusammenfassung Die wichtigsten Vertreter der hormonal aktiven Ovarialtumoren sind in der Gruppe der Keimstrang-Stromatumoren zusammengefasst. Sie machen weniger als 5% der Ovarialgeschwülste aus. Die Mehrzahl der Keimstrang-Stromatumoren besitzt die Fähigkeit zur Biosynthese von Steroidhormonen. Die pathologische Hormonbildung bewirkt spezifische Effekte an den hormonsensitiven Organen. Die klinischen Befunde sind abhängig von Art und Intensität der Hormonproduktion und vom Lebensalter der Patientin. In der Dignität stehen die Keimstrang-Stromatumoren als fakultativ maligne Geschwülste zwischen den nichtinvasiven (Borderline-) und den invasiven epithelialen Tumoren des Ovars. Neben den speziellen zur Hormonbiosynthese befähigten Ovarialgeschwülsten (Keimstrang-Stromatumoren, Steroidzelltumoren) können benigne und maligne Ovarialtumoren verschiedenen Typs aufgrund einer Vermehrung und/oder Stimulation von nicht-neoplastischen Zellen im Ovarialstroma endokrine (östrogene oder androgene) Aktivität aufweisen.

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261. Lavage oder Ultraschall beim stumpfen Bauchtrauma

Zusammenfassung 453 Patienten mit nachgewiesenem oder vermutetem stumpfen Bauchtrauma wurden geschallt. In 71% wurde kein pathologischer Befund, in 11% eine freie Blutung, in 8% eine retroperitoneale Blutung and in 7% eine Organeinblutung gefunden. In 2% fand sich eine Thoraxverletzung bzw. einmal eine Herzbeuteltamponade. Bei 111 Patienten erfolgte zusätzlich die Lavagierung. Bei einer Prävalenz von 37% and Spezifit von 97% betrug die Sensitivität für den Ultraschall 88% and für die Lavage 93%.     

Role of x-ray computed tomography in the preoperative evaluation of aneurysm of the abdominal aorta

The authors have studied the files of 50 consecutive patients (1987-89) operated for abdominal aortic aneurysm (AAA) and examined with CT. The criteria for inclusion were surgical features. CT can be made more accurate for the study of AAA: Thus the location of the neck of the aneurysm relative to the renal arteries was defined in 94% of all cases. In addition, CT yields information about the wall of the aneurysm, whether it be thickened (3 inflammatory aneurysms were properly diagnosed) or, mor importantly, weakened (solution of continuity in the wall in the "prior-to-rupture" appearance). Owing to the quality of its performances and to its noninvasive character, the authors regard CT with contrast injection as an essential technique for the preoperative assessment of abdominal aortic aneurysm in most cases. The examination must be carried out strictly, especially for the contiguous sections of the renal arteries and their extension to the crural arch. As it demonstrates weakened areas more easily, a more accurate study of the aneurysmal wall with CT might increase the surgical indications for some smaller aneurysms, the potential evolution of which does not seem to be associated with their diameter only.     

Human intestinal diamine oxidase (DAO) activity in Crohn's disease: A new marker for disease assessment?

The key-enzyme for the metabolism of diamines in man is diamine oxidase (DAO). Its highest activities are in the intestinal mucosa, localized in the cytoplasm of the mature enterocytes of the small and large bowel. If the gut is affected by inflammation in Crohn's disease macroscopical changes are observed. This prospective study investigated if these mucosal alterations are also reflected in changes of mucosal diamine oxidase activity and/or mucosal histamine content respectively. Twenty patients (12 female, 8 male; age: , range 18 49 years) undergoing gut resection because of complications in Crohn's disease (Jan.–Dec. 1988) formed the basis of the study. Tissue samples of the resected material from areas inflamed and histologically not involved in the disease were investigated for diamine oxidase activities and histamine content. Diamine oxidase activities in the mucosa obtained from the macroscopically normal proximal (155.6; (76–393) mU/g ( range)) and distal (132; (58.5–295) mU/g) resection margins were similar to our previous findings. In all patients, however, samples from the diseased mucosa had significantly (ca. 50%) lower diamine oxidase activities (74.5; (5–262) mU/g) compared to the healthy tissue. Similar differences were found in material obtained either from whole intestinal wall or from the mucosa. The determination of diamine oxidase activity constitutes possibly a more unambiguous and earlier parameter for assessing the extent of the inflamed area than histological disease presentations. Using biopsies the necessary extent of resection could be estimatedbefore operation: this may influence operative strategies and help in the definition of the minimum amount of inflamed gut to be removed.Supported by grant of Deutsche Forschungsgemeinschaft (Lo 199/15-2).     

Therapy of primary breast cancer in the 21st century: A prediction

Biology

New treatment selection criteria will arise from molecular biology parameters of growth and treatment response, most probably coupled with the increasing use of initial chemotherapy and repeated minimally invasive surgery.

Prevention

Secondary and hopefully also primary prevention of breast cancer will become more and more successful in the era of molecular genetics, and such interventions will be more directed to individuals and groups at defined higher risk.

Surgery

Surgery will increasingly tend towards “minimally invasive surgery,” which favors not only cosmetics and quality of life, but also more appropriate imaging follow-up.

Chemotherapy

Primary (preoperative) chemo- and endocrine therapy will become the standard initial form of breast cancer treatment, with the intent of down-staging of the tumors to allow later breast-conserving procedures, but also to use the tumor as a biological response parameter and hopefully also for better clinical outcome.

Cost — Effectiveness

Economical parameters might become more and more decisive, as we will have to live with much more “evidence based medicine” and with much more restricted allocation of resources in the future. This might mean, that we will have to diligently develop more simple and cheaper, but not prognostically worse treatment strategies in years to come. More specifically: Do we still need all of the traditional steps in diagnosis and treatment of breast cancer in order to achieve the same results?

Gain of Life

Finally in all of this, we have to make clearcut assumptions, supported also by society and people involved: How do we value “gained years of life” in breast cancer adjuvant and prevention trials? This certainly is not predominantly a medical or economical, but rather an ethical, social and political problem, which has to be finally answered by our socio-cultural environment, and not by doctors alone.