[Hemolysis and metastatic cancer in an elderly man]. / Iäkkään miehen hemolyysi ja levinnyt syöpä.

Sometimes correct diagnoses is reached after many years and even after decades. Our patient had for decades suffered from a hemolytic disease, life-threatening, metastatic cancer at the age of almost 90 years was also suspected. The patient was finally diagnosed as having mild hereditary spherocytosis and the associated paraspinal extramedullar hematopoiesis as well as an osteoporotic vertebral fracture caused by osteoporosis.

[Future of gynecological exfoliative cytology specimen, the Pap test]. / Gynekologisen irtosolunäytteen, papakokeen tulevaisuus.

Screenings of cervical cancer in Finland by using the Pap test have decreased the incidence of the disease by approx. 80%. Automation-assisted cytology and liquid-based Pap test have improved the technical quality of cytological examination. The HPV test allows the prevention of more cancers and its negative predictive value is crucially better than that of the Pap test. Its problem is the modest specificity in young age groups. When the HPV-vaccinated age groups reach the screening age, the HPV test should be adopted as the first-line screening test in all age groups. The Pap test will continue to have an important role as a further investigation and diagnostic specimen.

[Prolonged abdominal discomfort, ascites and pleural fluid]. / Pulmallinen vatsavaiva, askites ja pleuraneste.

A 67-year-old man had been examined for 1.5 years for hypersedimentation, abdominal discomfort and pleural effusion, but the cause had remained unclear. With progressive weight loss the patient was admitted to the ward for examinations, whereupon the diagnosis of a rare disease began to unravel.

[Reporting of thyroid fine needle samples is changing in Finland--the Bethesda system in thyroid cytology]. / Bethesda-järjestelmä kilpirauhasen sytologiassa.

A recommendation for the reporting of thyroid cytological specimens was made as the consensus of the expert meeting arranged by the U.S. National Cancer Institute (NCI). This Bethesda system will replace the former Papa classes also in thyroid cytology. The new Bethesda classification considers the representativeness of the thyroid specimen, and the classification is based on the correlation of the underlying histological change with the cytological report. In particular, follicular tumors and suspicion of them are separated from other tumors into their own group. The new system will bring about a significant improvement to the reports of thyroid cytological specimens.

HPV DNA testing as an adjunct in the management of patients with low grade cytological lesions in Finland.

BACKGROUND: Patients with recurrent low grade cytological abnormalities are at increased risk for high grade lesions. We wanted to see whether these patients could be identified by HPV DNA and pap tests. METHODS: A prospective study of 663 patients referred for a colposcopy on the basis of ASC-US or LSIL cytology. High-risk HPV DNA positivity and cytology were compared with histology. RESULTS: In total 65.6% samples were positive for HC2, and the overall proportion of CIN2+ lesions was 14.6%. No CIN2+lesions were found in patients testing HC2-, pap-. There were 5/97 (5.2%) high grade lesions, which were HC2-negative but pap-positive, including 1 cervical adenocarcinoma in situ. The corresponding histological sections were all positive for p16INK in immunostaining. In further analysis by PCR, 3 samples were positive for HPV DNA. High-risk HPV type 67, which is not included in the HC2 probe cocktail, was found in 1 case, and 2 cases were HPV positive but could not be typed. One CIN3 and one AIS remained HPV negative. In these 5 cases, the concomitant pap smear showed ASC-USx1, LSILx1, HSILx2 and AGCx1. During 6-month follow-up, a relatively high number of CIN2+(28/557, 5.0%) emerged from the non-CIN-CIN1 group. CONCLUSIONS: The HC2 test or pap test alone were not sensitive enough to detect all CIN2+lesions. A relatively high number of CIN2+cases emerged from the non-CIN-CIN1 group after 6 months. Adequate follow-up of patients with mild cytological abnormalities, including a repeat pap smear taken during colposcopy and control at 6 months is underscored. Combination of hrHPV DNA and pap test should be considered, since it had high negative predictive value.

Valinomycin-induced apoptosis of human NK cells is predominantly caspase independent.

Human NK cells are sensitive to the exogenous toxic compound valinomycin. This toxin, produced by Streptomyces griseus in moisture damaged buildings, induces apoptosis by dissipating the membrane potential in mitochondria. In this paper, we show that valinomycin-induced apoptosis involves two different pathways in human NK cells: the predominant one is caspase-3 independent and the other caspase-3 dependent. Resting human NK cells were found to contain high amounts of active caspase-3 as compared to the T cells in which high caspase-3 activity has been shown only after stimulation. Exposure to valinomycin did not alter the caspase-3 activity of human NK cells but induced nucleosomal fragmentation of DNA. General caspase inhibitor, Z-VAD-FMK, inhibited completely the caspase-3 activity, reduced DNA cleavage but did not prevent the spontaneous or valinomycin-induced apoptosis of NK cells. The endogenous high caspase-3 had only a slight effect on the major functions of human NK cells, i.e. cytotoxicity or gamma-IFN production, giving us a reason to suspect that the biological role of caspase-3 in NK cells could be the elimination of potentially harmful NK clones through apoptosis.

Inhibition of natural, interleukin-2 stimulated and bacillus Calmette-Guerin enhanced cytotoxicity with anti-CD16 antibodies.

PURPOSE: We studied the cytolytic mechanism of nonstimulated, bacillus Calmette-Guerin (BCG) stimulated and interleukin (IL)-2 (Chiron Corp., Amsterdam, The Netherlands) stimulated peripheral blood mononuclear cells. MATERIALS AND METHODS: We inhibited the cytotoxicity of nonstimulated, BCG stimulated and IL-2 stimulated peripheral blood mononuclear cells against various target cells using 3 monoclonal antibodies directed against the CD16 receptor of natural killer cells or alternatively monoclonal antibodies against the alpha and beta subunits of the IL-2 receptor complex (IL-2R). The main target cell was the poorly differentiated transitional cell line T24. RESULTS: Of the 3 anti-CD16 antibodies tested only CLB FcR-gran/1 effectively inhibited natural, IL-2 stimulated and BCG enhanced cytotoxicity. Cytotoxicity was also markedly diminished after depletion of CD16+CD56+/- cells with CLB FcR-gran/1. An hour of pretreatment with CLB FcR-gran/1 was enough to reduce significantly the level of cytotoxicity evoked by overnight stimulation with BCG or IL-2. Simultaneous administration of anti-IL-2Ralpha and anti-IL-2Rbeta significantly decreased the killing of target cells by BCG stimulated and IL-2 stimulated peripheral blood mononuclear cells. CONCLUSIONS: Within the stimulation times chosen the same killing mechanisms seemed to explain the nonstimulated, BCG stimulated and IL-2 stimulated cytotoxicity with CD16 positive cells as central effectors. Anti-CD16 antibodies may deliver a target cell independent down-regulatory signal to natural killer cells or alternatively mimic a nonIg ligand and block the detection of the target cell.