Functional characteristics of intraepithelial lymphocytes from mouse small intestine. III. Inability of intraepithelial lymphocytes to induce a systemic graft-versus-host reaction is because of failure to migrate in vivo.

In this study we have investigated whether addition of bone marrow accessory cells or concurrent administration of recombinant IL-2 would allow intraepithelial lymphocytes (IEL) to induce a systemic, lethal GvHR in irradiated hosts. In addition we have studied the ability of IEL to migrate into lymphoid tissues after intravenous injection and compared this with their locomotor capacity in vitro.     

Thromboembolieprophylaxe bei minimal-invasiven Eingriffen und kurzstationärer Behandlung Ergebnisse einer multicentrischen, prospektiven, randomisierten, kontrollierten Studie mit einem niedermolekularen Heparin

Zusammenfassung. Mit dem Ziel, die Incidenz tiefer Venenthrombosen bei selektierten Patienten nach laparoskopischer Cholecystektomie und anderen minimal-invasiven chirurgischen Eingriffen zu bestimmen, sowie die Sicherheit und Wirksamkeit eines niedermolekularen Heparinpr?parats (NMH) in der postoperativen Thromboseprophylaxe zu belegen, wurde eine prospektive, randomisierte, kontrollierte klinische Studie durchgeführt. Dabei wurden 718 Patienten nach Randomplan einer von 2 Prüfgruppen zugeordnet: Eine Gruppe erhielt physikalische Ma?nahmen zur Thromboseprophylaxe, wie Kompressionsstrümpfe mit graduiertem Andruck (n = 359), die 2. Gruppe erhielt ebenfalls physikalische Ma?nahmen und zus?tzlich ein NMH (Reviparin-Natrium, Clivarin) s. c. einmal t?glich (n = 359). Aus Sicherheitsgründen mit Hinblick auf die medikament?s unbehandelte Kontrollgruppe wurden Patienten mit 3 oder mehr Risikofaktoren für eine ven?se Thromboembolie nicht in die Studie aufgenommen. Die Diagnostik tiefer Beinvenenthrombosen erfolgte mittels Duplexscan. In dieser, eher künstlichen Niedrigrisikoselektion war die Gesamtincidenz thromboembolischer Ereignisse überraschend gering: 5 Verdachtsf?lle einer Lungenembolie, von denen nur 1 Lungenembolie szintigraphisch verifiziert werden konnte, sowie eine phlebographisch best?tigte Unterschenkelthrombose. Die Anwendung von Reviparin zur Prophylaxe ven?ser Thromboembolien war sicher und anwenderfreundlich – die Incidenz postoperativer Blutungskomplikationen betrug nur 2,3 % in der NMH-Gruppe und war somit sogar geringfügig niedriger als in der Kontrollgruppe (3,2 %). Die tats?chliche Incidenz tiefer Venenthrombosen bei Patienten nach laparoskopischer Cholecystektomie bleibt jedoch nach wie vor unklar. Weitere klinische Studien müssen in einem unselektierten Patientengut durchgeführt werden.      

Changes in liver and L-cell plasma membranes during infection with Coxiella burnetii.

Changes in plasma membrane proteins of guinea pig liver and L-929 cells were studied during infection with Coxiella burnetii. Polypeptide species resolved by disc polyacrylamide gel electrophoresis with sodium dodecyl sulfate showed quantitative but no qualitative differences between uninfected and infected samples. When the O'Farrell technique of isoelectric focusing, followed by sodium dodecyl sulfate-slab gel polyacrylamide gel electrophoresis, was employed, additional polypeptides were resolved. Livers and L cells were labeled with [3H]-glucosamine. Infected livers incorporated less [3H]glucosamine in the membrane proteins than uninfected material, presumably indicating lower glycoprotein levels. Infected L-cell membranes incorporated greater amounts of [3H]glucosamine, and also were labeled to a greater extent than uninfected membranes, employing the [125I]lactoperoxidase technique. Uninfected L cells showed a greater agglutinability with concanavalin A than did infected cells. Infected livers had much greater levels of cyclic adenosine 3',5'-monophosphate. The data indicate changes in plasma membranes as a result of infection. Possible physiological consequences of membrane changes are discussed.     

Lysosomal response of a murine macrophage-like cell line persistently infected with Coxiella burnetii.

The lysosomal response of a murine macrophage-like tumor cell line (J774) during persistent infection with Coxiella burnettii was examined. By using acid phosphatase as a lysosomal marker, it was shown that phagosome-lysosome fusion occurred in J774 cells persistently infected with C. burnetii. This observation was verified using thorium dioxide, an electron-dense compound that is sequestered in secondary lysosomes. The phagolysosomes contained viable replicating rickettsiae. Spectrofluorometric analysis indicated that the phagolysosomal pH of persistently infected cells was acidic. In attempts to correlate rickettsial survival with lysosome function, the activities of several lysosomal enzymes were assayed in both infected and uninfected cells. Activities of acid phosphatase and beta-acetylglucosaminidase were not significantly altered during infection. However, infected cells appeared to display slightly higher intracellular lysozyme, beta-glucuronidase, and beta-galactosidase activities.     

Familial pericentric inversion of chromosome 8

Eight children from seven presumably unrelated families were identified independently as having an unbalanced recombinant chromosome resulting in the presence of extra material on the short arm of a chromosome 8. Parental chromosomes were analyzed, and one member of each couple (four fathers and three mothers) was found to carry a pericentric inversion of a chromosome 8 [inv(8)(p23q22)]. The propositi had an unbalanced recombinant chromosome [rec(8),dup q,inv(8)(p23q22)]. The affected infants all had developmental delay, congenital heart disease, and unusual appearance. A common origin of the pericentric inversion was suggested because of geographic location and Mexican--American ancestry of the seven families.     

Bilateral synchronous granulomatous orchitis: gray-scale and colour Doppler sonographic findings

A 60-year-old man presented with impotence ultrasonography demonstrated bilateral irregular hypoechoic infiltration of testes and normal epididymis. Colour Doppler sonography showed only peripheral but no intralesional flow. Since the lesion was presumed as malignancy bilateral high inguinal orchiectomy was performed and bilateral idiopathic granulomatous orchitis was diagnosed. It was concluded that granulomatous orchitis should be considered in the differential diagnosis of diffuse testicular hypoechoic involvement which showed only peripheral low-resistance flow on colour Doppler sonography, in the proper clinical setting. Although this may be a helpful sign in the differential diagnosis of diffuse testicular infiltrations, high inguinal exploration remains mandatory.     

Angiogenesis in Vulvar Intraepithelial Neoplasia

Vulvar intraepithelial neoplasia (VIN) has been reported to be a precursor of invasive vulvar cancer. Switching to the angiogenic phenotype is considered a key step in tumor growth. Microvessel density (MVD) and vascular endothelial growth factor (VEGF), a highly angiogenic peptide, are important parameters of tumor angiogenesis. Forty-three histologic slides with 38 VIN I–III lesions were immunohistochemically stained for factor VIII-related antigen (F8-RA) and 44 slides with 37 VIN I–III for VEGF, since F8-RA reliably highlights tumor microvessels. Determination of MVD and VEGF expression was done by counting microvessels and VEGF-positive cells at a magnification of 200× and 400×. The highest concentration of F8-RA-stained MVD and VEGF expression was found at a small subepithelial area at the border of the VIN lesion to the stroma underneath but concentrations were low in all specimens of normal epithelium. High VEGF expression was significantly correlated to high MVD. For both MVD and VEGF expression the differences between VIN I and VIN III and between VIN II and VIN III were statistically significant (P< 0.0001). VIN III lesions are the clinical relevant precursors of invasive cancer of the vulva, as outlined by intense expression of VEGF protein and a highly dense network of microvessels underlying the dysplastic epithelium.     

Color-coded and spectral Doppler flow in breast carcinomas – Relationship with the tumor microvasculature

The phenomenon of tumor angiogenesis is an important aspect of understanding tumor biology. Studies in breast carcinoma have shown microvessel density (MVD) assessed by immunohistochemistry to be of prognostic importance in primary breast cancer. On the other hand, recently developed highly sensitive color-coded Doppler techniques offer a noninvasive method to examine neovascularisation in breast tumors. The purpose of this study was to determine the relationship between Doppler flow parameters and microvessel count assessed by immunohistochemistry. Fifty-three patients with primary breast cancer were examined preoperatively with color-coded Doppler ultrasound. The obtained Doppler frequency spectra were analyzed for peak systolic flow velocity (Vmax). Following surgery, paraffin-embedded microsections were immunohistochemically stained for factor VIII-related antigen. Tumor angiogenesis was assessed by microvessel count under light microscopy. Undifferentiated tumors correlated with high MVD (p=0.009) whereas other clinicopathological parameters were not associated with MVD. Color Doppler signals were detected in 50 out of 53 breast tumors. Evaluation of tumor flow velocity with various clinicopathological parameters showed a significant correlation with tumor size (p=0.0001) and lymph node metastasis (p=0.02). However, there was no significant correlation between MVD and intratumoral blood flow velocity assessed by color-coded Doppler. Our findings showed that Doppler flow measurement did not correlate with the extent of tumor angiogenesis of breast cancer. The present data give circumstantial evidence that microvessel count assessed by immunohistochemistry reflects the microvascular network, whereas tumor vasculature documented by Doppler ultrasound supplies information on the macrovasculature.