Effect of LHRH and its analogues on the progesterone secretion of human granulosa cells in vitro.

Progesterone secretion of cultured human granulosa cells treated with LHRH or its analogues was measured. Granulosa cells were also stimulated with LH, FSH, cAMP or forskolin. No differences could be observed in the progesterone basal secretion of cultures treated with or without LHRH or its analogues and after the various stimulations. It was concluded that the clinical experience that the sensitivity of ovaries for gonadotropins after LHRH desensitization is decreased could not be explained with the peripheral effects of LHRH on the granulosa cells. From the data obtained, the lack of LHRH receptors in the ovaries are suggested in humans.     

Effects of EPF treatment in human mononuclear cells.

Early Pregnancy Factor (EPF) is one of the earliest pregnancy associated signals, communicating the ensuing pregnancy to the maternal organism. Data published by others on the mouse suggest that EPF bound to spleen cells causes the release of two H2-restricted "suppressor factors" responsible for the rosette inhibiting activity of EPF in the rosette inhibition test. Using human material, we were able to detect the release of a second entity from mononuclear cells that is able to suppress rosette formation in the human rosette inhibition test. In an attempt to show an intracellular EPF effect in the target cell, cytosolic free calcium concentrations were measured in EPF-treated mononuclear cells from peripheral blood. Our findings did not, however, show any changes of intracellular free Ca(2+)-concentrations under the chosen conditions.     

Epidemiologie von Krebs während der Schwangerschaft

Zusammenfassung Die Diagnose Krebs in der Schwangerschaft ist ein seltenes Ereignis. Die Inzidenz wird auf 1:1000 geschätzt. Die am häufigsten diagnostizierten Krebsarten in der Schwangerschaft sind in absteigender Reihenfolge: Zervixkarzinom, Mammakarzinom, malignes Melanom, Hodgkin-Lymphom und akute Leukämien. In seltenen Fällen treten Schilddrüsenkarzinome, Non-Hodgkin-Lymphome, chronische Leukämien, maligne Ovarialtumoren, Kolon- und Nierenkarzinome auf. In einer populationsbasierten Studie der Jahre 1970–1979 konnte gezeigt werden, dass bei schwangeren Frauen im Alter von 15–19 Jahren die Inzidenz von Krebsfällen bei 2:100.000 Lebendgeburten lag. Im Alter von 40–44 Jahren war die Inzidenz 230:100.000 Lebendgeburten. Eine transplazentare Metastasierung ist selten. Krebsregister werden zukünftig mehr Informationen über den Zusammenhang von Krebs während der Schwangerschaft ermöglichen.     

Fusobacterium nucleatum GroEL induces risk factors of atherosclerosis in human microvascular endothelial cells and ApoE(-/-) mice

Infection and inflammation are risk factors in the initiation and progression of atherosclerosis. Periodontitis is one of the most prevalent chronic inflammations of the oral cavity, and has been reported to be associated with systemic disease. In this study, we evaluated whether the heat-shock protein GroEL of Fusobacterium nucleatum, one of the most prevalent bacteria in periodontitis, induces factors that predispose to atherosclerosis in human microvascular endothelial cells (HMEC-1) and apolipoprotein E-deficient (ApoE(-/-)) mice. GroEL induced the expression of chemokines such as monocyte chemoattractant protein-1 and interleukin-8 as well as cell adhesion molecules, such as intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and E-selectin. GroEL induced the activity of tissue factor and reduced the activity of the tissue factor pathway inhibitor. Foam cell formation was induced by GroEL. GroEL-injected ApoE(-/-) mice showed significant atherosclerotic lesion progression compared with control mice. Serum levels of risk factors for atherosclerosis such as interleukin-6, C-reactive protein, and low-density lipoprotein were increased in GroEL-injected ApoE(-/-) mice compared with control mice, whereas serum levels of high-density lipoprotein were decreased. We could detect significantly higher levels of anti-F. nucleatum GroEL antibody in serum and F. nucleatum DNA in gingival crevicular fluid from patients with periodontitis than in that from healthy subjects. Our results indicate that the host response to the GroEL of periodontal pathogens like F. nucleatum may be a mechanism involved in atherosclerosis, supporting the association of periodontitis and systemic infection.     

Substance P regulates macrophage inflammatory protein 3alpha/chemokine C-C ligand 20 (CCL20) with heme oxygenase-1 in human periodontal ligament cells

Although substance P (SP), a potent proinflammatory peptide, is involved in inflammation and immune responses, the effect of SP on the expression of macrophage inflammatory protein 3alpha[MIP-3alpha, chemokine C-C ligand 20 (CCL20)] in periodontal ligament (PDL) cells is unknown. Equally enigmatic is the link between SP, the stress protein heme oxygenase-1 (HO-1), and CCL20 production. We investigated whether SP induces the release of chemokine CCL20 from immortalized PDL (IPDL) cells, and further clarify SP-mediated pathways. We also examined the relationship between HO-1 and CCL20 by treating PDL cells with SP. Incubating IPDL cells with SP increased expression of CCL20 mRNA and CCL20 protein in a dose-time-dependent manner. Highly selective p38 and extracellular-regulated kinase 1/2 (ERK1/2) inhibitors abrogated SP-induced expression of CCL20 in IPDL cells. SP is also responsible for initiating phosphorylation of IkappaB, degradation of IkappaB and activation of nuclear factor (NF)-kappaB. SP induced expression of HO-1 in both a concentration- and time-dependent manner, and CCL20 reflected similar patterns. The inductive effects of SP on HO-1 and CCL20 were enhanced by HO-1 inducer hemin and the membrane-permeable guanosine 3',5'-monophosphate (cGMP) analogue 8-bromo-cGMP. Conversely, this pathway was inhibited by the HO-1 inhibitor zinc protoporphyrin IX (ZnPP IX) and the selective inhibitor of guanylate cyclase, 1H-(1,2,4)oxadiazole(4,3-a)quinoxalin-1-one (ODQ). We report herein the pathway that connects SP along with other modulators of neuroimmunoregulation to the induction of HO-1 and the inflammatory mediator macrophage inflammatory protein (MIP)-3alpha/CCL20 in IPDL cells, which play an important role in the development of periodontitis or inflammation during orthodontic tooth movement.     

Short- and long-term outcome after lung resection for invasive pulmonary aspergillosis

BACKGROUND: Lung resection for invasive pulmonary aspergillosis (IPA) is controversial. Neutropenia, thrombopenia and poor general condition may increase perioperative morbidity and mortality, and the redeeming benefit is questionable. Therefore we analyzed short- and long-term outcome after lung resection for IPA. METHODS: 41 patients with hematological disease underwent lung resection for suspected IPA: lobectomy (23 patients), wedge-resection (16) and enucleation (2). RESULTS: 4 (10%) patients developed major complications: pleural aspergillosis, bronchial stump insufficiency, severe bleeding, ARDS. 11 (27%) patients showed minor complications: pleural effusion (6), pneumothorax (2), seroma (2) and hematothorax (1). 30-day mortality was 10 % (4 of 41 patients): two died of bacterial septicemia, two of disseminated aspergillosis. One (2%) death was possibly surgery-related. IPA was cleared in 87% of patients, fungal relapse occurred in 4 (10%) patients. Overall survival was 65%, 58% and 40% at 6 months, 12 months and 5 years. CONCLUSION: Lung resection for IPA even in profound cytopenia is feasible with acceptable morbidity and mortality. Fungal infection can be cured in more than 80 % of patients. Long-term outcome can be achieved if the hematological disease is under control.     

Preliminary experiences with sentinel lymph node detection in cases of vulvar malignancy

Lymph node status is the most important prognostic factor in vulvar malignancy. The aim of this pilot study was to explore the clinical significance of radionuclide lymphoscintigraphy in the management of vulvar neoplasms. Eight patients with squamous cell carcinoma and two patients with malignant melanoma of the vulva were studied with 100 MBq technetium-99m nanocolloid (Sentiscint, OSSKI, Budapest) 1 day before surgery. The location of the sentinel lymph node was checked by a single-head gamma camera-computer system (MB 9200, Mediso, Budapest). Vulvectomy with bilateral inguinofemoral lymphadenectomy was performed in each case. At lymphadenectomy, the sentinel lymph node was separately removed and histologically studied. Three of the ten patients had positive sentinel lymph nodes (micrometastasis). Five months later one of them had local recurrence of the vulvar cancer, and another had inguinal recurrence of the tumour 6 months postoperatively; the third patient was operated on only recently. Our preliminary results are impressive and suggest that lymphoscintigraphy is an easy and reliable method for detection of the sentinel lymph node in vulvar malignancy.     

Recurrent pregnancy losses and the role of immunotherapy

Post implantation pregnancy losses are psychologically and economically stressful to the childbearing population. The etiology in the vast majority of cases is unknown but is partly thought to result from a breakdown of the maternal tolerance to the fetoplacental unit. Immunologically based therapy remains controversial but no alternative therapy is available at the moment. This article reviews the conceived immunological basis of recurrent pregnancy losses, discussing the controversies arising, and recommending the use of intravenous immunoglobulin, IVIg, in well controlled experiments for further clinical trials. Received: August 1999 / Accepted: 10 December 1999