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Testicular germ cell tumours (TGCT) represent the most common malignancy in young males. We reported previously that two prototype members of the mitogen-activated protein kinase (MAPK) family, the MAPK ERK kinase (MEK) and extracellular signal-regulated kinase (ERK), are inactive in malignant testicular germ cells and become active after drug stimulation, leading to apoptosis of tumour cells. In this study, we asked whether the protein phosphatase PP2A, a known inhibitor of the MEK-ERK pathway, participates in the proliferation and/or apoptosis of primary TGCT (n = 48) as well as two TGCT cell lines (NTERA and NCCIT). Quantitative RT-PCR, immunohistochemistry, western blot analyses and phosphatase assay indicate that primary TGCT as well as TGCT cell lines express PP2A and that PP2A is active in TGCT cell lines. The inhibition of PP2A by application of two PP2A inhibitors, cantharidic acid (CA) and okadaic acid (OA), results in a significant increase in caspase-3-mediated apoptosis of TGCT cell lines. Thereby, PP2A inhibition was accompanied by phosphorylation and activation of MEK and ERK. Functional assays using the MEK inhibitor PD98059 demonstrated that the phosphorylation of MEK and ERK was required for the induction of caspase-3-mediated apoptosis of malignant germ cells. Thus, our data suggest that inhibition of PP2A mediates its apoptosis-inducing effect on TGCT through activation of the MEK-ERK signalling pathway that leads to caspase-3-mediated apoptosis of tumour cells. In addition our results support previous observations that PP2A exerts an anti-apoptotic effect on malignant tumour cells.

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AIM: The selectivity of a water jet (WJ) is already used with clinical advantage in the surgery of liver, brain, kidney and herniated lumbar discs. The aim of the present study was to determine whether a WJ can be used for synovectomy without damaging the joint capsule and the cartilage. METHOD: 60 human cadaver knee specimens (67 +/- 14 years) were dissected into synovial and cartilage samples. They were randomly assessed to four pressure groups (pW = 3; 6; 9; 12 MPa) and three jet surface angles (beta = 30; 60; 90 degrees) The nozzle diameter was dD = 0.12 mm, the stand off distance of the jet was s = 10 mm with a feed rate of vV = 2 mm/s. The acquired parameters were depth of the cuts, histological layer, and change of the samples thickness. RESULT: There was a correlation of the cutting depth and the pressure (pW), whereas the jet-surface angle (beta) showed no correlation. The synovial layer of the cut likewise correlated with the pressure. At pW = 6 MPa the stratum subsynoviale could be cut selectively without damaging the fibrous capsule or the cartilage. The increase of the samples thickness was caused by an interstitial oedema. CONCLUSION: The different mechanical properties of the joint capsule and the stratum subsynoviale lead to the selective cutting of the water jet. Since the joint capsule was not damaged, the feasibility of WJ synovectomy has been proven. The device can be used for synovectomy in parts of the joint that are not visible as well as in very small joints.

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In 1993, pulmonary fat embolism occurred in 92 cases (17%) out of 527 clinical autopsies. It was found in 62% of patients who had suffered bone fractures, in 9% with soft tissue surgery and in 53% after resuscitation; non-traumatic fat embolism was present in 6% of the cases. The comparison group of 50 persons with lethal polytrauma revealed pulmonary fat embolism in 52% of the cases. Bone-marrow embolism and microthrombi accompanied fat embolism of the lungs; furthermore some of the persons with pulmonary fat embolism also expressed minor degrees of renal (55%) and cerebral (25%) fat emboli. A retrospective analysis of the clinical data revealed no specific symptoms: a so called fat embolism syndrome had not been discovered clinically in any of the cases with histologically proven fat embolism. The significance of pulmonary fat embolism as a cause of death with regard to histological and clinical findings is discussed.

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To our knowledge this is the first reported case of a primary extracranial meningioma located in the palatine tonsil. Immunohistochemical investigation of the tumour showed coexpression of vimentin and neuron-specific enolase (NSE). No staining was found with antibodies against cytokeratins KL1, 13/10, 8 and 18, epithelial membrane antigen EMA and melanoma protein (HMB-45). It seems justifiable to classify this tumour as an atypical meningioma because of the local increased mitotic activity.

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Adhesive (retractile) capsulitis of the hip joint is a rare complication (association) of (juvenile) diabetes mellitus. The clinical features, plain radiographic and CT findings and histomorphological appearances of this condition are described and attention is drawn to changes in the elastic tissue in the fibrosed capsule. Three diagnostic radiological features have been defined; in their presence, arthrography or diagnostic arthroscopy need not be performed.

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Ultrasonically guided fine needle biopsies were carried out in 84 patients with focal liver lesions and were subsequently evaluated histologically. A correct diagnosis of malignancy was made in 46 of 52 patients with proven hepatic malignancy, showing an overall accuracy of 93%. The specificity of the procedure was 100%. Such histological examination not only enables the differentiation between primary and secondary hepatic malignancy; it has the additional advantage of making a more precise tumour description and at the same time it pinpoints the primary site of the tumour.

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We report on the elastin, collagen and ground substance compartments in the human meniscus and their interrelationships. Elastin is found in neonates and shows both an arrangement parallel to the collagen fibre and into net-like structures. Branching, caliber inconstancy, rupture and the phenomenon of the "rubber band" are findings within the different forms of the meniscopathy. The function of the elastin compartment cannot be visualised without suggesting "puncta fixa". The morphology of the collagen-elastin-junctions has been described and their possible mode of function is discussed with the help of a model.

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The consideration is based on a finite urn model (drawn balls are not returned). One important conclusion is that increasing effects of selection on the surviving population are to be assumed only by selection of death. Inaccuracy of official death rates results from insufficiency in registration of the confidential part of death certificates. 57% (in females) and 58% (in males) of all malignant tumors (based on examinations in the presented autopsy material) are found beyond the age of 60. More rare than expected are multiple tumors: formal arguments for this are discussed, the phenomenon being explained by a considerably increased death rate. The spectrum of target organs for metastases in the age groups (over 60 years) is tabulated for the oesophagus, stomach, colon-rectum, lung, mamma and prostata as primary tumor localization. As it matastasizes each primary tumor localization shows a specific time course and a specific organ selection. The correlation between malignant tumors and concomitant non tumorous diseases is given special attention. The latter are regarded as indicator for the pathogenesis of tumor diseases. The conclusions are that the remaining population in the urn model is highly selected. This becomes more pronounced in the older and most advanced age groups.

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Death certificates for all clinics of the University of Heidelberg are centrally filled in at the University Pathology Institute. The certificate which accompanies the body gives the information for the official death certificate. There were 6263 autopsies between 1974 and 1978. The entry in the death certificate was compared with the complete morbid-anatomical diagnosis. Sensitivity and positive correctness showed many errors, the proportion of false-negative diagnoses being nearly three times higher than false-positive ones.

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Monometric DNA impulse cytophotometry of ploidism state (diploid or aneuploid tumors with stemmline shift, polyploidism ) and proportion of DNA-synthesized cells (S-phase proportion) were determined on over 500, mostly malignant, tumors of different sites. The results were compared with histopathological findings (TNM stage and degree of differentiation). Large diploid carcinomas of the oral cavity have lower S-phase activity than aneuploid tumors. Carcinomas of the breast, stomach and ovary are frequently diploid. Aneuploid carcinomas of these regions generally have high synthesizing activity. Mucoid signet-ring carcinomas of the stomach have lower S-phase activity than non-mucoid carcinomas. In the colorectal region aneuploid carcinoma predominates, in the colon more than in the rectum. Tumor metastases from colon and rectum into the liver predominantly are from aneuploid primary tumors. For tumors of the breast, corpus uteri and ovary with high and moderate differentiation there is a direct correlation between histological grade of differentiation and the S-phase proportions. Aneuploid tumors vary from low to high synthesizing activity. Diploid meningioma and glioma have a low S-phase proportion, aneuploidism correlates with an increase in growth. Supplementation of histopathological diagnosis by determining ploidism and S-phase activity makes an important contribution in the assessment of the degree of malignancy, as well as for therapeutic purposes.

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A case report is given of a 46 year old person concerned professionally with melting gold, who exhibited bioptically and histologically verified lesions of the liver after chronic intoxication with cadmium. This patient was exposed throughout 8 years during his job activities to cadmium vapors. He exhibited during the time of investigation decreased renal function with tubular proteinuria as well as a polyneuropathy. In addition, hepatic lesions could be found, as small focal necrosis, fatty degeneration and fibrosis. Cadmium content of the liver was increased 13 times above normal.

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In an experimental comparative study on rabbits, the efficacy of the reduction of surface thrombus formation was investigated using heparinized central venous catheters compared with non-heparinized. Up to a central indwelling period of ten days, there was a reduction of the thrombus layer thickness on the heparinized catheters of 80% (with a trial duration of three days this was as much as 90%). The action of the stabilized surface heparin, which leads to a substantial thromboresistance, is complex in nature. 1) By intensified adsorption of plasma proteins in the early phase (proteins consist of antithrombin III, factor IX, X and XI), there is very much less thrombocyte adhesion and aggregation on the heparinized catheter surfaces. 2) The externally orientated negative net charge of the heparin shows a similar effect. 3) If there is thrombocyte adhesion despite this, further heparin effects become more prominent. Thus the release of ThF 3 and ADP, which leads to aggregation, is markedly inhibited. On the other hand, this leads to easier dissolution of already aggregated thrombocytes and on the other to a reduction of the catalytic thrombocyte surface for the plasma clotting factors. 4) This effect is supported by the increased adsorption of antithrombin III onto the control surface. 5) Finally there is also an inhibitory effect of heparin on the activated Stuart-Prower factor. Local thrombosis on the venous catheter surface can thus be effectively reduced by local therapy, without greater risks for the intensive care patient.

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The quantitative and semantic aspects of information contained in thesauri are discussed with regard to three types of thesaurus: a thesaurus without classification, with a hierarchical structure, and with a facet structure. The optimal structure for a thesaurus, from the quantitative point of view, will depend on the number of diagnoses, the number of subdivisions and on the frequency of the diagnoses and structures. The authors show how semantic information can be computed semi-quantitatively if the structures in a diagnosis can be designated as 'more' and 'less' important for the diagnosis in question. TDM, ICD and SNOP are compared in quantitative terms. About 70-80% of diagnoses of the circulatory system and respiratory system, but only 20% of diagnoses of the nervous system, were found to be directly transferable between TDM and ICD. With the post-co-ordinated SNOP about 80% of TDM diagnoses could be codified.

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