Ganglioglioma: A clinicopathological study of 10 cases

The clinical, radiological, and pathological features in 10 cases of ganglioglioma are described. The clinical data were derived from the patients' medical records, including a review of the age, sex, details of the presenting symptoms, radiological imagings, surgical intervention, and the clinical outcome. Age ranged from 1 to 66 years (mean 29); there were five males and five females. The tumors were located in the fronto-medial, bifrontal, temporal, temporo-basal, temporo-parieto-occipital, and parietal lobes; the 3rd ventricle; the cervicothoracic spinal cord; and the conus medullaris. The presenting symptoms were focal seizures, headaches, hemiparesis, paraparesis, and tetraparesis. In four patients, gross total resection was achieved and in the remaining six patients only subtotal resection was possible. Tumor recurrence occurred in three patients, 1 year, 14 months, and 2 years after the first operation. The histopathologic appearance of gangliogliomas showed a broad variation of the neuronal, glial, and stromal component. Studying proliferation characteristics, labeling for Ki-67 ranged from 0 to 13.7% (mean 4.1) and for PCNA from 0 to 32.1% (mean 20.4). Due to their favorable prognosis, early recognition and correct diagnosis are important in order to avoid progressive neurological deficits and unnecessary aggressive therapy. The application of immunohistochemistry for both neuronal (synaptophysin, NSE, NFP) and astrocytic (GFAP) cell markers, as well as proliferation markers, are recommended in the diagnostic setting for gangliogliomas. The treatment of choice is total surgical resection. The role of radio- and chemotherapy is still controversial.     

Inhibition of angiotensin converting enzyme by ramipril in serum and tissue of man.

Studies in animal models have indicated that ramipril is a potent inhibitor of angiotensin converting enzyme (ACE) in serum and tissue. In our study, the normal range of ACE activity and the inhibitory effect of short-term oral administration of ramipril on ACE activity in human serum and tissue samples of renal cortex, heart and blood vessels were determined. ACE activity in the renal cortex (125.2 +/- 11.5 nmol/mg per min) was greater than 600 times that of the heart (0.20 +/- 0.01 nmol/mg per min), greater than 500 times that of the veins (0.23 +/- 0.09 nmol/mg per min) and greater than 150 times that of the arteries (0.80 +/- 0.23 nmol/mg per min). ACE activity in the renal cortex and arteries 2 h after last dosing was almost completely inhibited by ramipril whereas ACE activity in the veins and heart was inhibited to a lesser extent. Our results demonstrate in man, for the first time, an inhibition of tissue ACE following short-term oral treatment with an ACE inhibitor.     

Actions of growth factors on plasma calcium. Epidermal growth factor and human transforming growth factor-alpha cause elevation of plasma calcium in mice.

Specific humoral substances produced and secreted by human tumors that cause hypercalcemia have not been identified. Certain growth factors (such as epidermal growth factor, platelet-derived growth factor, and transforming growth factors-alpha and -beta) have been shown to stimulate the resorption of bone in organ culture by both prostaglandin-dependent and prostaglandin-independent pathways. In this report we demonstrate that epidermal growth factor and recombinant human transforming growth factor-alpha induce a significant rise in plasma calcium concentration when administered repeatedly to intact mice for periods ranging from 24 h to 16 d. The elevation of plasma calcium is not dependent on dietary calcium and is not invariably accompanied by an increase in systemic levels of the prostaglandin E2 metabolite 13,14-dihydro-15-keto-prostaglandin E2. The in vivo calcium-mobilizing activity of epidermal growth factor and transforming growth factor-alpha indicate that these or related growth factors need be considered as potential mediators of tumor-induced hypercalcemia.     

In vitro Virulenz wundinfizierender Staphylokokken-Isolate von schwerbrandverletzten Patienten

Zusammenfassung 30Staphylococcus aureus Stämme von drittgradig verbrannten Patienten wurden hinsichtlich ihrer Fähigkeit zur Hämolysingenerierung und ihres Vermögens zur Histaminfreisetzung aus Mastzellen (RPMC) untereinander verglichen. Die bakteriellen Kulturüberstande von 8 Stämmen aus Wundbiopsien zeigten signifikant niedrigere in vitro Aktivitäten als die übrigen Staphylokokken-Kulturüberstände. Bei dem Vergleich der in vitro Aktivitäten der gewaschenen Bakterienzellen ergab sich ein umgekehrtes Verhältnis. Diese Befunde zeigen, daß beiS. aureus Isolaten, welche zum Zeitpunkt einer invasiven Brandwundeninfektion isoliert werden können, die mikrobiellen Pathogenitätsfaktoren an die Bakterienzelle gebunden bleiben.

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In vitro measurement of pathogenicity ofStaphylococcus aureus isolated from heavily burned patients

Summary The hemolysin and histamine releasing activity of 30S. aureus strains isolated from third degree burns of heavily burned patients was detected. The culture supernatants (cs) ofStaphylococcus aureus isolated during episodes of invasive burn wound infection displayed significantly lower amounts of hemolysin and histamine releasing activity as compared to cs of bacteria isolated when no sign of septicemia was present. In contrast, when washed bacterial cells were analysed, a reversed ratio could be observed. These data clearly indicate that in strains isolated during invasive burn wound infection pathogenicity factors remain attached to the bacterial surface of the staphylococci investigated.

Gefördert durch das Bundesamt für Zivilschutz (ZS 8-122-42)     

LSECtin interacts with filovirus glycoproteins and the spike protein of SARS coronavirus

Cellular attachment factors like the C-type lectins DC-SIGN and DC-SIGNR (collectively referred to as DC-SIGN/R) can augment viral infection and might promote viral dissemination in and between hosts. The lectin LSECtin is encoded in the same chromosomal locus as DC-SIGN/R and is coexpressed with DC-SIGNR on sinusoidal endothelial cells in liver and lymphnodes. Here, we show that LSECtin enhances infection driven by filovirus glycoproteins (GP) and the S protein of SARS coronavirus, but does not interact with human immunodeficiency virus type-1 and hepatitis C virus envelope proteins. Ligand binding to LSECtin was inhibited by EGTA but not by mannan, suggesting that LSECtin unlike DC-SIGN/R does not recognize high-mannose glycans on viral GPs. Finally, we demonstrate that LSECtin is N-linked glycosylated and that glycosylation is required for cell surface expression. In summary, we identified LSECtin as an attachment factor that in conjunction with DC-SIGNR might concentrate viral pathogens in liver and lymph nodes.     

Immature B cells from human and mouse bone marrow can change their surface light chain expression

The capacity of bone marrow-derived surface immunoglobulin-positive (sIg⁺) human and mouse immature B cells, generated either in vitro or in vivo, to change their light (L) chain expression, has been assayed by the number of cells which change in vitro from one type of L chain to the other type, or to no sIg at all. Immature sIg⁺ B cells were generated in vitro from sIg^? precursor cells from human or mouse bone marrow. The immature sIg⁺ cells expressed RAG-1. Human sIg⁺ cells expressed xfr; and λ L chains in ratios between 1:1 and 3:1, whereas in mouse cells, this ratio ranged from 10:1 to 20:1. Upon reculture of the human and mouse xfr;⁺sIg⁺ cells, about half of them remained xfr;⁺, a quarter became λ⁺, and another quarter became sIg^?. Between 1 and 3% expressed both xfr; and λ chains. Of the human λ⁺ cells, about two-thirds remained λ⁺, only 1 to 2% became xfr;⁺, while the other third became sIg^?. Again, between 1 and 3% expressed both xfr; and λ L chains. These results indicate that expression of sIgM in the B cell membrane does not terminate L chain gene rearrangement, and that some order exists in xfr; versus λ gene rearrangements. Hence, human and mouse xfr;⁺ immature B cells can become λ⁺, but very few of the λ⁺ cells can become xfr;⁺, and both can become sIg^?. Further, human CD10⁺/sIg⁺ xfr;⁺ and λ⁺ cells and mouse B220^low/sIg^low xfr;⁺ cells enriched from bone marrow, i.e. immature B cells differentiated in vivo, changed their Ig phenotype upon in vitro culture, but in lower frequencies. By contrast, human and mouse mature B cells did not change their L chain or Ig phenotype. Hence, at least a part of the sIg⁺ immature B cells in bone marrow retain the capacity to change their L chain and Ig phenotype, and this capacity is lost when they become mature, peripheral B cells.     

Ligand and cytokine dependence of the immunosuppressive pathway of tryptophan catabolism in plasmacytoid dendritic cells

Murine plasmacytoid dendritic cells (pDCs) have been credited with a unique ability to express indoleamine 2,3-dioxygenase (IDO) function and mediate immunosuppression in specific settings; yet, the conditions of spontaneous versus induced activity have remained unclear. We have used maneuvers known to up-regulate IDO in different cell types and have examined the relative efficacy and mechanisms of the induced activity in splenic pDCs, namely, after specific receptor engagement by CTLA-4-Ig, CD200-Ig or CD28-Ig, the latter in combination with silenced expression of the suppressor of cytokine signaling 3 (SOCS3) gene. We found that pDCs (CD11c+ mPDCA-1+ 120G8+) do not express IDO and are not tolerogenic under basal conditions. B7-1 engagement by CTLA-4-Ig, CD200R1 engagement by CD200-Ig and B7-1/B7-2 engagement by CD28-Ig in SOCS3-deficient pDCs were each capable of initiating IDO-dependent tolerance via different mechanisms. IFN-gamma was the major cytokine responsible for CTLA-4-Ig effects, and type I IFNs for those of CD200-Ig. Immunosuppression by CD28-Ig in the absence of SOCS3 required IFN-gamma induction and IFN-like actions of IL-6. Therefore, although pDCs do not mediate IDO-dependent tolerance constitutively, multiple ligands and cytokines will contribute to the expression of a tolerogenic phenotype by pDCs in the mouse.