MR imaging in adenocarcinoma of the prostate: interobserver variation and efficacy for determining stage C disease.

Patients with adenocarcinoma of the prostate confined to the gland (stage B) are candidates for a potentially curative surgical procedure (radical retropubic prostatectomy). However, patients with adenocarcinoma that penetrates the capsule or invades the seminal vesicles (stage C) are no longer considered good candidates for surgical cure of their disease. The purpose of this study was to compare the ability of four radiologists to detect stage C disease on MR images and to evaluate interobserver variability. One hundred consecutive MR studies of the prostate were reviewed independently by four radiologists to determine whether the cancer was stage C (capsule penetration or seminal vesicle invasion by tumor). A radical prostatectomy was performed in each case, and careful histologic assessment was made of the prostatic capsule and seminal vesicles for any evidence of stage C disease. The sensitivity, specificity, and accuracy (true-positive + true-negative/100 patients) in detecting stage C disease were calculated for each of the four readers. Four receiver-operating-characteristic curves were generated and compared by means of the univariate z score. Percentage agreement was calculated for five specific areas of the prostate on MR images, and observations made by the best reader were compared with the other three to help determine interreader variability. The results showed that the sensitivity and specificity of MR imaging in detecting stage C disease ranged from .24 to .61 (mean, .48) and .49 to .79 (mean, .66), respectively. The accuracy of MR imaging ranged from .47 to .61 (mean, .55). The univariate z score test showed that one of the readers significantly differed from the other three. The average percentage agreement between that reader and the other three was 70% for the five separate anatomic regions. This study shows that considerable interobserver variation exists in the interpretation of MR images for staging cancer of the prostate. The average accuracy among four radiologists in determining the presence of stage C adenocarcinoma of the prostate from MR images was only slightly above a chance guess at .55.     

Serum sAPO-1/Fas levels in multiple sclerosis

Soluble APO-1 (sAPO-1) may prevent apoptosis of lymphocytes induced by activation of the APO-1/Fas receptor. Objectives – To determine sAPO-1 levels in the serum of multiple sclerosis (MS) patients and controls in order to investigate if abnormal lymphocyte apoptosis occurs in this disease. Methods – Serum samples from patients with MS, other neurological diseases, systemic lupus erythematosus and healthy controls were determined by enzyme-linked immunosorbent assay. Results – We did not detect differences in mean serum sAPO-1 levels between patients with multiple sclerosis and controls. Conclusions – This preliminary study suggests that resistance of peripheral blood lymphocytes to apoptosis mediated by sAPO-1 is not likely to be a major factor in the development of autoreactive cells in MS.     

Assessing the quality of cesarean birth data in the Demographic and Health Surveys

Cesarean section surgery is the clinical response used to prevent several of the leading causes of maternal and perinatal mortality and morbidity. Given the deficient state of health-information systems in most developing countries, nationally representative surveys are currently the most widely available source of population-based cesarean birth data. The purpose of this study is to assess the quality and internal consistency of Demographic and Health Survey cesarean birth data across countries and time periods. Although these surveys are highly standardized, the formulation of the question on cesarean birth and the categories of women who are asked the question often differ across surveys. A skip pattern that restricts the cesarean question to women who delivered in a health-care facility improves the internal consistency of the data, although in some countries cesarean deliveries are still reported at low-level, presumably nonsurgical facilities. Recommendations are made for improving data analysis and the future collection of population-based cesarean birth data.     

Participation of CD45, NKR-P1A and ANK61 antigen in rat hepatic NK cell (pit cell)mediated target cell cytotoxicity

AIM Several triggering receptors have been described to be involved in natural killer (NK) cellmediated target cytotoxicity. In these studies, NK cells derived from blood or spleen were used. Pit cells are liver-specific NK cells that possess a higher level of natural cytotoxicity and a different morphology when compared to blood NK cells. The aim of this study was to characterize the role of the NK-triggering molecules NKR-P1A, ANK61 antigen, and CD45 in pit cell-mediated killing of target cells. METHODS 51 Cr-release and DNA fragmentation were used to quantify target cell lysis and apoptosis, respectively. RESULTS Flow cytometric analysis showed that pit cells expressed CD45, NKR-P1A, and ANK61 antigen. Treatment of pit cells with monoclonal antibody ( mAb ) to CD45 ( ANK74 ) not only inhibited CC531s or YAC-1 target lysis but also apoptosis induced by pit cells. The mAbs to NKRP1A (3.2.3) and ANK61 antigen (ANK61) had no effect on pit cell-mediated CC531s or YAC-1 target cytolysis or apoptosis, while they did increase the Fcγ receptor positive (FcγR+) P815 cytolysis and apoptosis. This enhanced cytotoxicity could he inhibited by 3,4-dichloroisocoumarin, an inhibitor of granzymes. CONCLUSION These results indicate that CD45 participates in pit cell-mediated CC531s and YAC-1 target cytolysis and apoptosis. NKR-P1A and ANK61 antigen on pit cells function as activation structures against FcγR+ P815 cells, which was mediated by the perforin/granzyme pathway.     

Age-dependent myocardial reinduction of apoptosis inhibitors under VAD in heart failure

Hemodynamic unloading using the ventricular assist device [VAD] results in partial functional recovery of failing hearts that show increased susceptibility to cardiomyocyte apoptosis. The caspase cascade is the central element of the apoptotic process in cells. We therefore tested expression shifts of left ventricular mRNA of caspases and their endogenous inhibitors from 15 patients with VAD support and successful bridging to transplantation using semiquantitative RT-PCR. Cardiac unloading was shown by the reduction in ventricular Pro-ANP mRNA under VAD. No alteration of mRNA expression under VAD could be observed for initiator caspases, for their selective inhibitors or for apoptotic signal molecules from the mitochondrial intermembrane space. Only two unselective cardiac IAPs (inhibitor of apoptosis protein) were increased under VAD with better recovery in younger patients. In conclusion, our findings indicate that successful hemodynamic unloading by VAD support causes only minor, age-dependent recovery in the expression of IAPs, while presumed alterations in antiapoptotic modulator systems upstream of the caspase cascade still remain to be identified.     

Thymosin-α1, but not interferon-α, specifically inhibits anchorage-independent growth of hepatitis B viral transfected HepG2 cells

Background: Thymosin-α₁ is a biological response modifier that has been used clinically, alone and in combination with interferon-α for the treatment of chronic hepatitis B viral infection. Both immunomodulatory and immediate intracelluilar mechanisms have been postulated to explain the effect of these two agents on HBV-infected hepatocytes.Methods: In this study, hepatitis B transfected HepG2 hepatoblastoma cells (HepG2-Nu2), derived from 2.2.15 cells, were used as an in vitro model to determine the efficacy of thymosin-α₁ and interferon-α, individually and combined, a proliferation inhibitors of HBV-infected cells. For comparison, parental HepG2 cells and an SV40-transfected HepG2 cell line (HepG2P9T2) were also evaluated.Results: In a clonogenic soft agar assay, thymosin-α₁ inhibited the anchorage-independent growth of the HepG2-Nu2 cells by 40% compared with untreated controls, but did not inhibit parental HepG2 or HepG2P9T2 clonal growth. The response was dose dependent over concentrations spanning three log units. In comparison, 10 000 units/ml of interferon-α inhibited parental HepG2, HepG2-N4Z and HepG2P9T2 by 33%, 41% and 87%, respectively. The combination of thymosin-α₁ and interferon-α consistently inhibited HepG2-Nu2 clonal growth more effectively than either treatment alone, reaching maximum inhibition levels of 51%.Conclusions: Thymosin-α₁ specifically inhibits the tumorigenic growth of HBV-transfected HepG2 cells in contrast to the general inhibition displayed by interferon-α. This panel of cell lines may be an important resource for dissecting the mechanism by which thymosin, alone or in combination with other drugs, influences HBV-infected hepatocytes and/or HBV-associated carcinoma.     

Transmural differences in myocardial blood flow and in coronary dilatory capacity in hemodiluted conscious dogs

Summary In 16 conscious resting dogs regional myocardial blood flow and the local coronary dilatory capacity were studied with the particle distribution technique during isovolemic hemodilution (hct=13%). Postischemic peak coronary hyperemia following release of temporary circumflex coronary artery occlusion was used for quantification of regional coronary dilatory capacity. In hemodilution (arterial blood oxygen content less than one third of normal) left ventricular blood flow (LVBF) was 460±36 ml/100 g·min, subendocardial/subepicardial flow amounted to 1.3±0.1. During postischemic peak hyperemia LVBF increased by 33% up to 606±63 ml/100 g·min. This 33% increase in LVBF was distributed mainly to the subepicardial layer, while in the subendocardial layer there was no significant flow increase. It is concluded that the increase in heart rate and systolic coronary vascular compression in addition to the lowered arterial oxygen content lead to exhaustion of the dilatory reserve in the subendocardium during hemodilution. Therefore the remainingoverall dilatory capacity is without functional significance.

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Transmurale Unterschiede der Myokarddurchblutung und der Koronarreserve in wachen Hunden bei Hämodilution

Zusammenfassung Die Verteilung der Myokarddurchblutung und der Dilatationsreserve der Koronargefäße wurde in 16 wachen Hunden in Ruhelage mit der Partikelverteilungsmethode bestimmt bei isovolämischer Hämodilution. Die postischämische Hyperämie der Koronargefäße nach Eröffnung eines zeitweiligen Verschlusses der Zirkumflexarterie wurde zur Beurteilung der lokalen Dilatationsreserve herangezogen. Unter Hämodilution (mit einem arteriellen Sauerstoffgehalt von weniger als einem Drittel des Normalwertes) betrug die Durchblutung des linken Ventrikels 460±36 ml/100 g·min.Das Verhältnis von subendokardialer/subepikardialer Durchblutung betrug 1,3±0,1. Während postischämischer Hyperämie stieg die Ventrikeldurchblutung um 33% auf 606±63 ml/100 g·min. Diese 33% ige Durchblutungszunahme erstreckte sich hauptsächlich auf die subepikardiale Schicht der Ventrikelwand, während in der subendokardialen Schicht keine signifikante Durchblutungszunahme nachweisbar war. Es wird gefolgert, daß die Zunahme der Herzfrequenz und der systolischen Koronargefäßkompression zusammen mit dem erniedrigten arteriellen Sauerstoffgehalt zu dieser Erschöpfung der Dilatationsreserve in der Innenschicht unter Hämodilution führen. Deshalb ist die verbleibende gemittelte Dilatationsreserve der gesamten Ventrikelwand ohne funktionelle Bedeutung.

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With 3 figures and 2 tables     

A method for simultaneous study of the karyotype, morphology, and immunologic phenotype of mitotic cells in hematologic malignancies

A major problem in the cytogenetic analysis of hematologic neoplasms has been an inability to identify the cell from which the chromosomes were obtained. We describe a procedure that allows simultaneous analysis of karyotype and cell cytology in mitotic cells. The method differs from conventional cytogenetic analysis in that after mild hypotonic treatment, the cells are cytocentrifuged onto glass slides. In mitotic cells, this procedure often results in adequate spread of the chromosomes within the intact cell membrane. The cytoplasmic structure also remains intact, so that cytologic preparations are of good quality. Morphologic and immunologic identification of mitotic cells can be done using routine hematologic stains, such as Giemsa or Sudan black B, and various antisera using immunofluorescence techniques. The chromosomes can be simultaneously analyzed either without banding on slides stained with Giemsa or with Q-banding on slides stained with immunofluorescence techniques. Identification of numerical and structural karyotype aberrations thus is possible in morphologically identified cells.