Dietary vitamin E does not inhibit the promotion of liver carcinogenesis by polychlorinated biphenyls in rats

In this study, the effect of dietary vitamin E on the hepatic tumor-promoting activity of PCB-77 and PCB-153 in female Sprague-Dawley rats (175-200 g) was investigated. One week after diethylnitrosamine injection, rats were fed purified diets containing 10, 50, or 250 mg/kg vitamin E in the form of alpha-tocopheryl acetate. Starting 1 wk later, we injected rats i.p. with vehicle (corn oil) or PCB-77 or PCB-153 (300 mumol/kg) every 14 d for 4 injections. All rats were killed 10 d after the last PCB injection. The number and volume of placental glutathione S-transferase (PGST)-positive foci were increased by PCB-77 but not by PCB-153. Vitamin E did not affect the induction of PGST-positive foci. PCB-77, but not PCB-153, increased hepatic NF-kappaB activity. In conclusion, dietary vitamin E supplementation does not protect against the induction of altered hepatic focal lesions by PCBs.     

Delayed chemokine receptor 1 blockade prolongs survival in collagen 4A3-deficient mice with Alport disease

Human Alport disease is caused by a lack of the alpha3-, 4-, or 5-chain of type IV collagen (COL4A). Affected humans and COL4A3-deficient mice develop glomerulosclerosis and progressive renal fibrosis in the presence of interstitial macrophages, but their contribution to disease progression is under debate. This question was addressed by treating COL4A3-deficient mice with BX471, an antagonist of chemokine receptor 1 (CCR1) that is known to block interstitial leukocyte recruitment. Treatment with BX471 from weeks 6 to 10 of life improved survival of COL4A3-deficient mice, associated with less interstitial macrophages, apoptotic tubular epithelial cells, tubular atrophy, interstitial fibrosis, and less globally sclerotic glomeruli. BX471 reduced total renal Cll5 mRNA expression by reducing the number of interstitial CCL5-positive cells in inflammatory cell infiltrates. Intravital microscopy of the cremaster muscle in male mice identified that BX471 or lack of CCR1 impaired leukocyte adhesion to activated vascular endothelium and transendothelial leukocyte migration, whereas leukocyte rolling and interstitial migration were not affected. Furthermore, in activated murine macrophages, BX471 completely blocked CCL3-induced CCL5 production. Thus, CCR1-mediated recruitment and local activation of macrophages contribute to disease progression in COL4A3-deficient mice. These data identify CCR1 as a potential therapeutic target for Alport disease or other progressive nephropathies associated with interstitial macrophage infiltrates.     

Mucinous carcinoma of the skin, primary, and secondary: a clinicopathologic study of 63 cases with emphasis on the morphologic spectrum of primary cutaneous forms: homologies with mucinous lesions in the breast

We present the largest series of mucinous carcinoma involving the skin, describing the histopathologic, immunohistochemical, electron microscopic, and cytogenetic findings. Our aim was fully to characterize the clinicopathologic spectrum and compare it with that seen in the breast. In addition, we wished to reevaluate the differential diagnostic criteria for distinguishing primary mucinous carcinomas from histologically similar neoplasms involving the skin secondarily, and study some aspects of their pathogenesis. We demonstrate that primary cutaneous mucinous carcinomas span a morphologic spectrum compatible to their mammary counterparts. Both pure and mixed types can be delineated morphologically, and some lesions have mucocele-like configurations. Most lesions seem to originate from in situ lesions that may represent, using mammary pathology terminology, ductal hyperplasia, atypical ductal hyperplasia, or ductal carcinoma in situ or a combination of the three. Inverse cell polarity appears to facilitate the progression of the changes similar to lesions in the breast. The presence of an in situ component defines the neoplasm as primary cutaneous, but its absence does not exclude the diagnosis; although for such neoplasms, full clinical assessment is essential. Mammary mucinous carcinoma involving the skin: all patients presented with lesions on chest wall, breast, axilla, and these locations can serve as clue to the breast origin. Microscopically, cutaneous lesions were of both pure and mixed type, and this correlated with the primary in the breast. Dirty necrosis was a constant histologic finding in intestine mucinous carcinomas involving the skin, and this feature may serve as a clue to an intestinal origin.     

Über die Osteochondrosis intervertebralis L V/S I als Ursache der Kreuzschmerzen bei Frauen

Zusammenfassung In der vorliegenden Arbeit wird angestrebt, an Hand der Literatur und eigener Untersuchungen einige vermutlich zur Osteochondrosis intervertebralis L V/S I beitragende Momente zu prüfen.Nach Beschreibung des pathologisch-anatomischen Bildes und des Röntgenbefundes bei Osteochondrosen werden die anatomisch-physiologischen Verhältnisse im Lumbosacralbereich erörtert und die Bedeutung des Lumbosacral- und des Keilformwinkels für das Zustandekommen einer Osteochondrosis intervertebralis L V/S I untersucht und die Resultate dieser Überlegungen mit den sich statistisch ergebenden Werten des an der Universitäts-Frauenklinik Erlangen erhobenen Materials verglichen. Dabei konnte die Ansicht, daß die Osteochondrose eine früher als die Spondylose auftretende Verschleißerscheinung sei, nicht bestätigt werden, da sich bei dem vorliegenden Material ein verstärktes Auftreten der Osteochondrose ebenfalls erst nach dem 50. Lebensjahr ergab. Dagegen darf die Theorie, daß ein abnormer, besonders aber ein verkleinerter Lumbosacralwinkel bei der Entstehung einer Osteochondrose pathogenetisch in Betracht kommt, nach unseren Ergebnissen als wahrscheinlich angesehen werden.Die vom physikalisch-physiologischen Gesichtspunkt aus gesehen als bestehend zu bezeichnende Konstruktion, daß ein abnormer Keilformwinkel zur Schädigung der 5. Lendenwirbelscheibe und daher zur Entstehung einer Osteochondrosis intervertebralis L V/S I wesentlich beitragen müsse, konnte durch unsere Untersuchungen nicht gestützt und damit auch die Ergebnisse der Arbeit von W.-D. Müller nicht bestätigt werden.Mit 7 Textabbildungen (10 Einzelbilder)     

53. Gynäkologische Bemerkungen zum Problem der fehlenden Vagina

Langenbeck's Archives of Surgery - Vor operativer Herstellung eines künstlichen Vaginalrohres muß eine Differenzierung des Krankheitsbildes erfolgen. Ferner muß geklärt...