Kosten-Nutzenanalyse beim Mammographie-Screening

Zusammenfassung Bei Frauen von 50 bis 69 Jahren ist in schwedischen Mammographie-Screening-Studien eine Reduktion der Mortalit?t an Brustkrebs langfristig bis zu 30 % beobachtet worden. Bei Frauen von 40 bis 49 Jahren ist eine geringe Verminderung der Sterblichkeit beobachtet worden, die nicht signifikant ist. Die Strahlenbelastung von 2,4 mGy für 2 Ebenen-Mammographie einer Brust führte auch nach Langzeit-Beobachtungen (über 20 Jahre) nicht zu einer Vermehrung neue auftretender Brustkrebsquellen. Die Vorteile des Screenings bezüglich Minderung der Sterblichkeit, h?ufigere Anwendung von brusterhaltenden Therapien und Senkung des durchschnittlichen Tumordurchmessers im Screening auf weniger als die H?lfte des Durchmessers im Vergleich zu Kontrollkollektiven führt dazu: Ein qualit?tsgesichertes Screening ab 50 bis 70 Jahren ist für Deutschland zu empfehlen. Für jüngere Frauen müssen weitere Studien den m?glichen Vorteil des Screenings abkl?ren. Im dezentralen Versorgungssystem sollte das Screening von niedergelassenen ?rzten in Zusammenarbeit mit Krankenh?usern erfolgen, wo die Doppelbefundung, die Abkl?rung unklarer F?lle (Assessment) und die fortlaufende Kosten-Nutzen-Analyse (Evaluation) erfolgen sollte. Qualit?tssicherungszentren, Referenz- und Ausbildungszentren sind zu fordern. Auch die Mammographie der kurativen Versorgung profitiert von einem Screening-Programm. Eingegangen am 29. M?rz 1996 Angenommen am 1. April 1996     

Functional aspects of serotonin transmission in the basal ganglia: a review and an in vivo approach using the push-pull cannula technique

Peripheral deafferentation of the rodent olfactory bulb results in loss of dopamine content, tyrosine hydroxylase activity and immunocytochemical staining for tyrosine hydroxylase in juxtaglomerular dopamine neurons. Reinnervation of the bulb by afferent neurons results in the return of all parameters to control levels suggesting that the dopamine neurons did not degenerate but that the expression of tyrosine hydroxylase enzyme was transneuronally regulated in a static population of juxtaglomerular cells. To evaluate this possibility, we determined the activity and immunocytochemical localization of the second enzyme in the dopamine biosynthetic pathway, DOPA decar?ylase. At a time when tyrosine hydroxylase activity was reduced to 25% of control values, DOPA decar?ylase activity in the lesioned bulb was maintained at about 65% of that in the unlesioned bulb. Immunocytochemical staining with antibodies to both enzymes, performed sequentially in the same sections, demonstrated that in the unlesioned bulb tyrosine hydroxylase and DOPA decar?ylase are co-localized in the same population of juxtaglomerular neurons. Similar results were obtained in adjacent sections each stained with one of the two antibodies. In contrast, in the deafferented bulb, about three times as many neurons were stained with DOPA decar?ylase as with tyrosine hydroxylase antibodies. The DOPA decar?ylase activity measurements and immunocytochemistry argue for the continued presence, in the lesioned olfactory bulb, of a population of tyrosine hydroxylase deficient dopamine neurons.The data suggest that olfactory receptor cell innervation transneuronally regulates the expression of tyrosine hydroxylase by mechanisms separate from those controlling the levels of DOPA decar?ylase.     

Ras homolog gene family H (RhoH) deficiency induces psoriasis-like chronic dermatitis by promoting TH17 cell polarization

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Activity of human erythrocyte gangliosides as a receptor to HVJ

Liposomes could bind and fuse efficiently to human erythrocytes in the presence of HVJ when they contained gangliosides isolated from human erythrocytes. Sialosylparagloboside, which has a terminal sequence of NeuAcα2?3Ga1β1?4GlcNac, has a much higher receptor activity to the virus than GD_1a, GD_1b, GT_1b, and GT_1a, all of which contain the terminal sequence of NeuAcα2?3Galβ1?3GalNAc or NeuAcα2?8NeuAcα2?3Galβ1?3GalNAc. The activity of sialosylparagloboside is comparable to that of glycophorin, a major sialoglycoprotein of human erythrocytes, when compared on the basis of the required amount (as sialic acid) of compounds. The high affinity of sialosylparagloboside to the viral HANA protein is also suggested by the finding that it showed high inhibitory activity against HVJ-mediated binding of glycophorin liposomes to erythrocytes. Sialosylparagloboside was also highly susceptible to the viral sialidase, the other biological function of HANA protein.     

Marginalzonenlymphome: extranodale vom MALT-Typ, nodale und splenische

Marginal zone B-cell lymphomas (MCL) of extranodal, nodal and splenic origin appear to be different lymphoma entities with a similar growth pattern in the marginal zone of the B-follicles. Decisive for the detection of MCL as a distinct lymphoma entity was the "MALT concept" for lymphoid infiltrates in the gastric and intestinal mucosa as described by Isaacson et al. in the 1980's. Immunohistological stainings for the immunoglobulin light and heavy chains and molecular pathological studies of the immunoglobulin heavy chain gene configuration have subsequently confirmed the neoplastic nature of the extranodal infiltrates and differentiated marginal zone cells from mantle zone cells. In 1994, the MCL of MALT type as well as of nodal and splenic origin were included in the REAL classification and in 1998 in the new WHO classification for lymphomas. Meanwhile extranodal MCL of MALT-type have been observed in almost every organ and site of the body, by far most frequently in the gastric mucosa. Beside the typical growth pattern, lymphoepithelial lesions are a distinct diagnostic feature of extranodal MCL. Clinically, the small cell extranodal MCL show a very good prognosis with regression after treatment. As for nodal and splenic MCL, we need further studies to evaluate the prognostic aspects and to compare them with other B-cell lymphomas. The same is true for primary extranodal large B-cell lymphomas or blastic transformation to a large cell lymphoma; in these tumors the diagnosis of a MALT type lymphoma should only be made if a small cell component with MALT-specific criteria can be proved.     

Mutual inhibition of the binding of Clq and protein A to rabbit IgG immune complexes

A complex of rabbit IgG antibody with horseradish peroxidase covalently linked to Sepharose 4B was used as an insoluble immune complex for studying the binding of complement factor C1q protein A from Staphylococcus aureus, and its IgG-binding fragments AB and B, to rabbit IgG. It was shown that protein A (mol. wt approx. 42,000) and fragments AB and B (mol. wts approx. 14,000 and 7000, respectively) inhibited the binding of C1q to insoluble immune complex at 4 degrees C. However, at 37 degrees C fragment B did not inhibit this binding. On the other hand, C1q, when bound to an insoluble immune complex, almost completely blocked the binding of protein A and fragment B at both temps. The higher affinity of C1q for its CH2-binding site than of fragment B for its CH2-binding site may explain the displacement of the latter from the CH2 domain. The mutual inhibition of the binding of C1q and protein A (and its smaller fragments) indicates that the binding sites for C1q and protein A are closely located in the CH2 domain.     

Die onkozytäre Metaplasie/Neoplasie – Morphologie, Biochemie, Molekulargenetik

Zusammenfassung Die vorliegende Arbeit gibt eine übersicht über onkozyt?re Metaplasien- und Neoplasien. Dabei werden insbesondere biochemische, zytochemische und molekulargenetische Ergebnisse er?rtert. Bekannt ist, da? in onkozyt?ren Zellen der Nebenschilddrüse sowie auch der Leber bei Zirrhose verst?rkt Defekte der Atmungskette vorkommen. Die zugrundeliegenden molekulargenetischen Mechanismen sind jedoch noch ungekl?rt. Es ist anzunehmen, da? sich onkozyt?re Metaplasien pathogenetisch von onkozyt?ren Neoplasien unterscheiden. Zudem bestehen organabh?ngige Unterschiede in der Prognose onkozyt?rer Neoplasien. Beispielsweise kommen onkozyt?re Karzinome bevorzugt in der Schilddrüse vor, w?hrend sie in anderen Organen vergleichsweise selten sind. Welche molekulargenetischen Mechanismen hierfür verantwortlich sind, ist noch weitgehend unbekannt.      

Mikrokallusformationen der Spongiosa Ein bisher unterschätzter reparativer Mechanismus des Skelettsystems

Zusammenfassung Mikrokallusformationen lassen sich in nahezu allen Skelettabschnitten der Spongiosa nachweisen. Mikrokallus besteht aus Geflechtknochen, der sich an lokal überbelasteten Stellen in der Spongiosa bildet. Mit Hilfe einer speziellen Pr?parationstechnik wurden 26 skelettgesunde und 11 Wirbels?ulen von F?llen mit Osteoporose untersucht. Mikrokallusformationen finden sich bevorzugt bei Frauen ?lter als 45 Jahre in den unteren Wirbels?ulenabschnitten. Dabei hat die Mikroarchitektur der Spongiosa (TBPf) einen st?rkeren Einflu? auf die Anzahl der Mikrokalli, als individuelle Trabekelparameter (Tb.N, BV/TV und Tb.Th). Nur in 33 % der Formationen lassen sich Frakturspalten nachweisen. Mikrokallusformationen k?nnen nichtinvasive Knochenmassemessungen verf?lschen. Auch wenn Mikrokallusformationen Indikatoren für eine Instabilit?t der Spongiosa sind, tragen sie zur Knochenregeneration bei, und die Entstehung neuer Trabekel ist durch sie m?glich. Die Vorstellung, da? Osteoporose das Resultat einer verminderten Mikrokallusbildung ist, trifft nicht zu.      

Apoptose: Bcl-2 ein Schlüsselprotein für den programmierten Zelltod

Zusammenfassung Die Realisation, da? Tumorwachstum nicht nur durch Zellproliferation, sondern auch durch ein l?ngeres Zellüberleben bedingt sein kann, er?ffnet vollst?ndig neue Perspektiven in der Grundlagenforschung wie in der klinischen Tumorforschung. Die Apoptose ist deshalb heute Kernpunkt wissenschaftlicher Diskussion. Im Zentrum des derzeitigen Interesses ist neben den Steuermechanismen des programmierten Zelltodes auch der Nachweis seiner klinischen Bedeutung für die verschiedenen Tumorentit?ten. Aktuelle Untersuchungen zur Embryogenese, zum physiologischen Zellumsatz und zu epithelialen und hormonabh?ngigen Tumoren weisen das Protoonkogen bcl-2 als einen wichtigen Regulator der Apoptose aus. Nach eigenen Untersuchungen hat der Pathomechanismus Apoptose auch für maligne mesenchymale Tumoren eine Bedeutung.      

The nucleus basalis magnocellularis: The origin of a cholinergic projection to the neocortex of the rat

The cells of origin of a neocortical cholinergic afferent projection have been identified by anterograde and retrograde methods in the rat. Horseradish peroxidase injected into neocortex labelled large, acetylcholinesterase-rich neurons in the ventromedial extremity of the globus pallidus. This same group of neurons underwent retrograde degeneration following cortical ablations. The region in which cell depletion occurred also showed significant decreases in the activities of choline acetyltransferase and acetylcholinesterase. Discrete electrolytic and kainic acid lesions restricted to the medial part of the globus pallidus each resulted in significant depletions of neocortical choline acetyltransferase and acetylcholinesterase. Hemitransections caudal to this cell group did not result in such depletions. Taken together these observations suggest that the acetylcholinesterase-rich neurons lying in the ventromedial extremity of the globus pallidus, as mapped in this study, constitute the origin of a major subcortical cholinergic projection to the neocortex. The utility of acetylcholinesterase histochemistry in animals pretreated with di-isopropylphosphorofluoridate in identifying cholinergic neurons is discussed in the light of this example; specifically, it is proposed that high acetylcholinesterase activity 4–8 h after this pretreatment is a necessary, but not sufficient, criterion for the identification of cholinergic perikarya.The neurons in question appear to be homologous to the nucleus basalis of the substantia innominata of primates, and are thus termed ‘nucleus basalis magnocellularis’ in the rat. No evidence was obtained to support the hypothesis that nucleus of the diagonal band projects to neocortex. However, striking similarities in size and acetylcholinesterase activity were observed among the putative cholinergic perikarya of the nucleus basalis magnocellularis, the nucleus of the diagonal band, and the medial septal nucleus.Kainic acid lesions of the neocortex produced uniform and complete destruction of neuronal perikarya. These lesions decreased neocortical glutamic acid decar?ylase activity, suggesting that there are GABAergic perikarya in the neocortex. However, the same lesions did not affect neocortical choline acetyltransferase. This observation suggests that there are no cholinergic perikarya in the neocortex, a conclusion that is consistent with the absence of intensely acetylcholinesterase-reactive neurons in the neocortex.