Meiotic gene activation in somatic and germ cell tumours.

BACKGROUND: Germ cell tumours are uniquely associated with the gametogenic tissues of males and females. A feature of these cancers is that they can express genes that are normally tightly restricted to meiotic cells. This aberrant gene expression has been used as an indicator that these cancer cells are attempting a programmed germ line event, meiotic entry. However, work in non-germ cell cancers has also indicated that meiotic genes can become aberrantly activated in a wide range of cancer types and indeed provide functions that serve as oncogenic drivers. Here, we review the activation of meiotic factors in cancers and explore commonalities between meiotic gene activation in germ cell and non-germ cell cancers. OBJECTIVES: The objectives of this review are to highlight key questions relating to meiotic gene activation in germ cell tumours and to offer possible interpretations as to the biological relevance in this unique cancer type. MATERIALS AND METHODS: PubMed and the GEPIA database were searched for papers in English and for cancer gene expression data, respectively. RESULTS: We provide a brief overview of meiotic progression, with a focus on the unique mechanisms of reductional chromosome segregation in meiosis I. We then offer detailed insight into the role of meiotic chromosome regulators in non-germ cell cancers and extend this to provide an overview of how this might relate to germ cell tumours. CONCLUSIONS: We propose that meiotic gene activation in germ cell tumours might not indicate an unscheduled attempt to enter a full meiotic programme. Rather, it might simply reflect either aberrant activation of a subset of meiotic genes, with little or no biological relevance, or aberrant activation of a subset of meiotic genes as positive tumour evolutionary/oncogenic drivers. These postulates provide the provocation for further studies in this emerging field.

A concise review of significantly modified serological biomarkers in giant cell arteritis, as detected by different methods.

Giant cell arteritis (GCA) is a primary systemic vasculitis present in subjects older than 50years with involvement of large- and medium-sized arteries. Early diagnosis for GCA is essential to prevent serious complications, such as permanent vision loss and/or cerebrovascular events. Elevated inflammatory cytokines, with acute phase and other proteins dominate large- and medium-sized arteries leading to stenosis or occlusion of arterial lumen. To date, there are no reliable serological markers for monitoring GCA. The review aims to provide concise overview of published GCA studies in order to: a) identify significantly changed serological biomarkers in GCA and compare the influences of techniques for marker evaluation and b) investigate most promising markers in GCA using analyte frequency and meta-analysis.

Relative survival of patients with non-malignant central nervous system tumours: a descriptive study by the Austrian Brain Tumour Registry.

BACKGROUND: Unlike malignant primary central nervous system (CNS) tumours outcome data on non-malignant CNS tumours are scarce. For patients diagnosed from 1996 to 2002 5-year relative survival of only 85.0% has been reported. We investigated this rate in a contemporary patient cohort to update information on survival. METHODS: We followed a cohort of 3983 cases within the Austrian Brain Tumour Registry. All patients were newly diagnosed from 2005 to 2010 with a histologically confirmed non-malignant CNS tumour. Vital status, cause of death, and population life tables were obtained by 31 December 2011 to calculate relative survival. RESULTS: Overall 5-year relative survival was 96.1% (95% CI 95.1-97.1%), being significantly lower in tumours of borderline (90.2%, 87.2-92.7%) than benign behaviour (97.4%, 96.3-98.3%). Benign tumour survival ranged from 86.8 for neurofibroma to 99.7% for Schwannoma; for borderline tumours survival rates varied from 83.2 for haemangiopericytoma to 98.4% for myxopapillary ependymoma. Cause of death was directly attributed to the CNS tumour in 39.6%, followed by other cancer (20.4%) and cardiovascular disease (15.8%). CONCLUSION: The overall excess mortality in patients with non-malignant CNS tumours is 5.5%, indicating a significant improvement in survival over the last decade. Still, the remaining adverse impact on survival underpins the importance of systematic registration of these tumours.

Response of Deinococcus radiodurans to low-pressure low-temperature plasma sterilization processes.

AIMS: Characterize the response of Deinococcus radiodurans R1 cells to low-pressure low-temperature nitrogen-oxygen microwave plasma and identify repair processes during recovery. METHODS AND RESULTS: Cells coated onto glass slides exhibited a biphasic plasma inactivation kinetics. Treatment with various plasmas and subsequent incubation in recovery medium prolonged the lag phase in a part of the survivors, during which the ability to grow on stress medium was recovered. This recovery strongly depended on transcriptional and translational processes and cell wall synthesis, as revealed by addition of specific inhibitors to the recovery medium. Genes involved in DNA repair, oxidative stress response, and cell wall synthesis were induced during recovery, as determined by quantitative RT-PCR. Damage to chromosomal DNA caused by plasma agents and repair during recovery was directly shown by quantitative PCR. Plasmas with less UV radiation emission were also effective in killing D. radiodurans cells but resulted in less DNA damage and lower induction of the investigated genes. CONCLUSIONS: The response of D. radiodurans to plasma indicates that DNA, proteins, and cell wall are primary targets of plasma finally leading to the cell death. Protein oxidation is more important for killing of D. radiodurans cells than of Bacillus subtilis spores. Thus, the contaminating biological material affects the plasma composition to be used for sterilization. SIGNIFICANCE AND IMPACT OF THE STUDY: The results in this study provide new insight into the interaction of plasma with bacterial cells. This knowledge contributes to the definition of useful parameters for novel plasma sterilization equipment to control process safety.

Characterization of Bacillus subtilis spore inactivation in low-pressure, low-temperature gas plasma sterilization processes.

AIMS: To identify structural components of Bacillus subtilis spores serving as targets for sterilization with microwave induced low-pressure, low-temperature nitrogen-oxygen plasma. METHODS AND RESULTS: The inactivation of spores followed a biphasic kinetics consisting of a log-linear phase with rapid inactivation followed by a slow inactivation phase. In the course of plasma treatment, damage to DNA, proteins and spore membranes were observed by monitoring the occurrence of auxotrophic mutants, inactivation of catalase (KatX) activity and the leakage of dipicolinic acid, respectively. Spores of the wild-type strain showed the highest resistance to plasma treatment. Spores of mutants defective in nucleotide excision repair (uvrA) and small acid-soluble proteins (Delta sspA Delta sspB) were more sensitive than those defective in the coat protein CotE or spore photoproduct repair (splB). Exclusion of reactive particles and spectral fractions of UV radiation from access to the spores revealed that UV-C radiation is the most effective inactivation agent in the plasma, whereby the splB and Delta cotE mutant spores were equally and slightly less sensitive, respectively, than the wild-type spores. Finally, the extent of damages in the spore DNA determined by quantitative PCR correlated with the spore inactivation. CONCLUSIONS: Spore inactivation was efficiently mediated by a combination of DNA damage and protein inactivation. DNA was identified to be the primary target for spore inactivation by UV radiation emitted by the plasma. Coat proteins were found to constitute a protective layer against the action of the plasma. SIGNIFICANCE AND IMPACT OF THE STUDY: The results provide new evidence to the understanding of plasma sterilization processes. This knowledge supports the identification of useful parameters for novel plasma sterilization equipment to control process safety.

Characterisation of selected cadmium--zinc--telluride detectors.

The performance of new detection technologies like the ambient temperature cadmium--zinc--telluride (CdZnTe) detectors is of interest for search and identification of radioactive material in a range of applications. Various types of CdZnTe detectors that are currently available on the market as well as some specially designed ones were tested and characterised. The examination included peak shape, energy-resolution, energy-range and also the usability in hand-held applications. Additionally, the effects of the use of a cooling system were evaluated.

Investigation of food contamination since the Chernobyl fallout in Austria.

In a large-scale investigation the decrease of the activity concentration of 137Cs in foodstuffs after the widespread Chernobyl fallout was determined. At different times after the deposition in 1986 more than 1000 samples of various foodstuffs in Austria were taken and investigated with regard to their activity concentration. The investigation showed that in the first year after deposition, the activity concentration decreased to about 6-10% (milk, fruit), and 3-6%, respectively (grain, potatoes, vegetables) of the values in the fallout maximum. The calculated effective half-lives are significantly shorter than observed after nuclear weapon test series and result in a smaller long-term exposure than estimated before. The effective ingestion dose in the 50 years following of a one-time nuclear fallout amounts to about 1.3 times of the first year ingestion dose. In 2002, the ingestion dose in Austria amounts to 2.24 microSv (adult), or 0.88 microSv (5-year infant) respectively, which is less than 0.5% of the ingestion dose of the first year and amounts to 0.7% of the ingestion dose from natural radionuclides.

Carcinoma showing thymic-like elements--a rare malignancy of the thyroid gland.

BACKGROUND: Carcinoma showing thymic-like elements (CASTLE) is a rare tumour of the thyroid of thymic origin. The histological appearance of this tumour may be similar to that of squamous cell carcinoma of the thyroid, but outcome associated with CASTLE is more favourable. METHODS: A systematic literature review was conducted for case reports on CASTLE. A text word search of the Medline database was made with a manual search of the citations from these references. Twenty-two case reports were found. RESULTS: In five patients with tumour-negative lymph nodes no local or distant recurrence was observed. Seventeen patients had unknown or involved lymph nodes. Two patients were excluded from further study: one had no follow-up and one was treated by irradiation only. Of the remaining 15, six had local, three had distant and two had local and distant recurrence. In patients with involved or unknown lymph node status, local recurrence was noted in one of five patients treated by surgery and irradiation, and in seven of ten patients treated by surgery alone. Irradiation or systemic chemotherapy was given to four patients with recurrent tumours, with variable response. CONCLUSION: CASTLE with tumour-negative lymph nodes has a low risk of recurrence and surgery without adjuvant therapy is sufficient. Radiotherapy seems indicated when lymph nodes are tumour positive and can be effective for recurrent tumours. In selected patients surgery for recurrent tumour can improve quality of life and outcome.

Myocardial fatty acid metabolism during acute cardiac allograft rejection.

Fatty acids are promptly taken up, metabolised and eliminated by healthy cardiomyocytes. Cardiomyopathy, coronary heart disease and chronic rejection are known to be associated with an impaired fatty acid metabolism. It was the aim of this study to investigate fatty acid metabolism in a rat heart transplant model and to correlate scintigraphic findings with histological changes. After right-side nephrectomy of Lewis recipients Brown Norway cardiac allografts were anastomosed to the renal vessels. Animals were given no immunosuppression. The metabolism of carrier-free 17-123 jodo-heptadecanoic acid (123J-HDA) with a specific activity of > 2 x 10(17) Bq/ml was scintigraphically measured between days 1 and 11. An increase in the grade of rejection was observed over time. Fifty-six frames of 30 s duration each were recorded. For the region of interest (native heart, transplanted heart, left kidney) frames 10-56 were superimposed, time-activity curves generated and monoexponentially fitted. Furthermore, elimination half-life and intercepts were calculated. Following scintigraphic evaluation the animals were killed and graft as well as native hearts excised for histological examination. The uptake of the tracer identified severe grades of rejection. Elimination half-life of the tracer was twice as long from hearts with mild rejection and more than 14 times as long in severe rejection compared with no rejection. Elimination half-life and amplitude did not permit discrimination between grades 1, 2 and 3 a, but significantly decreased in groups 3 b and 4. This method therefore seems to be a valuable tool for the noninvasive detection of severe acute cardiac allograft rejection. Since fatty acid metabolism is clearly stress-dependent it remains to be seen whether this method allows detection of earlier rejection in loaded hearts.

[Immunological aspects of a child with idiopathic pulmonary hemosiderosis and celiac disease]. / Immunologische Aspekte bei idiopathischer Lungenhämosiderose und Zöliakie.

A case report of a girl aged 3.5 years affected by the extremely rare combination of idiopathic pulmonary haemosiderosis (IPH) and coeliac disease (CD) is presented. It is the 13th such case that has been published over the last 25 years and only the 7th to be reported in a child. We believe that the concurrence of these two diseases is not coincidental, because a gluten-free diet had beneficial effects on the pulmonary symptoms not only in our case but also in other such patients. However, the pathogenetic relation between IPH and CD remains unclear. Although circulating immune complexes were detected in our patient's serum, there was no evidence of their putative damaging effect on the basement membrane of the alveolar capillaries. Furthermore, no IgA deposits could be demonstrated in alveolar basement membranes. Therefore the hypothesis that there is a reaction between IgA reticulin or endomysial antibodies and an alveolar basement membrane antigen with consecutive structural damage is unlikely.

[A new method of orthotopic liver transplantation from the guinea pig to the rat]. / Eine neue Technik der orthotopen Lebertransplantation vom Meerschweinchen auf die Ratte.

Guinea pig to rat orthotopic liver transplantation is associated with serious technical problems contributing to impaired graft reperfusion and a high incidence of primary non function. In order to reduce the operation time and thereby organ damage during procurement a simplified technique for reconstruction of the infrahepatic vena cava was developed and is described in detail. Reduced operation time was associated with markedly improved lobular graft perfusion and significantly better graft survival. We suggest a modification of the donor operation for the guinea pig to rat xenograft liver model for the sake of reducing non immunological factors in this difficult setting.

[Predictive value of latex agglutination on Helicobacter pylori in children with recurrent abdominal pain]. / Praediktiver Wert einer Latex-Agglutination auf Helicobacter pylori bei Kindern mit rezidivierenden abdominellen Beschwerden.

In a prospective investigation, a rapid latex test for Helicobacter pylori in the serum (Pyloriset) was carried out in 39 patients with recurrent abdominal pain aged from six to 15 years. The test was positive in 19 patients. All of these children were subjected to gastroduodenoscopy. Seven cases showed a Helicobacter-associated chronic active antrum gastritis, whereas in the remaining 12 children gastritis not induced by Helicobacter or normal mucosa was found. Of the 20 Pyloriset-negative patients, only five could be biopsied. One of these showed a Helicobacter pylori-induced antrum gastritis. The latex test investigated had a positive predictive value which was too low (37%) to make it helpful in deciding for or against gastroduodenoscopy and the general anesthesia mostly associated with this.

Synovial metaplasia of the skin.

We present two female patients, aged 15 and 45 years, with synovial metaplasia of the skin. Both lesions, localized in the knee and hand respectively, arose after preceding local trauma. Case 1 had intradermal irregular cystic spaces in the adjacent myxoid stroma of which large polygonal eosinophilic cells were found. In contrast, case 2 was characterized by a longitudinal space within the lower dermis and subcutis which was lined by a membrane similar to hyperplastic synovium. The cells of the membrane showed an eosinophilic spindle shaped cytoplasm with processes towards the lumen. In both cases the eosinophilic cells, strongly suggestive of fibroblasts, showed staining for vimentin only, whereas no reactivity could be obtained with antibodies to actin, desmin, S-100 protein, Factor VIII related antigen, cytokeratin, epithelial membrane antigen, carcinoembryonic antigen and CD 68. The absence of CD 68 positivity differs from that seen in normal and hyperplastic synovium. Delayed wound healing around a nidus seems the most likely cause of the change.

[Urticarial vasculitis as a symptom of Muckle-Wells syndrome?]. / Urtikarielle Vaskulitis als Symptom des Muckle-Wells-Syndroms?

A patient is reported with a history of several years of chronic urticaria, transient fever, arthralgias and secondary systemic amyloidosis. A biopsy of an urticarial lesion showed necrotizing vasculitis and amyloid deposits in the eccrine sweat glands. Amyloid A deposits were also detected in kidney and rectum biopsies. This patient is likely to represent a variant of the Muckle-Wells syndrome (chronic relapsing urticaria, fever, arthralgia, deafness and renal amyloidosis). Hitherto undescribed is the presence of a necrotizing vasculitis as cause of the urticarial rash; further investigation will determine whether or not this finding represents the rule rather than an exception.

Cystectomy: the treatment of choice in patients with carcinoma in situ of the urinary bladder?

Patients (n = 46) with carcinoma in situ (Tis) of the urinary bladder were treated by intravesical chemotherapy. The complete remission rate was 75%. After a mean interval of 17 months recurrent tumours were diagnosed in 47%. Radical cystectomy with urethrectomy was performed in eight patients. Distal ureterectomy and uretercystoneostomy was done in six patients because of a distal ureteric tumour. Based on this group of 46 patients and the current literature, the following criteria are essential in indicating cystectomy: (1) micro-invasion; (2) persistent Tis after adequate intravesical treatment; (3) progressive tumour; (4) Tis of ureter and/or prostate; (5) tumour recurrence at more advanced stage.

[Xanthogranulomatous pyelonephritis in early childhood]. / Xanthogranulomatöse Pyelonephritis im Kleinkindesalter.

We report on a two-year-old infant boy in whom a tumorous enlargement of the left kidney which was not imaged in the excretion urogram was discovered by renal sonography after the second urinary tract infection. By synopsis of the clinical data and imaging techniques, but especially by the detection of foam cells in the urinary sediment, we were already able to make the diagnosis of a xanthogranulomatous pyelonephritis before the operation. Since diffuse infiltration of the entire organ was present, total nephrectomy was carried out as the therapy of choice. Besides the case report, in particular the difficulties in the diagnosis of this form of pyelonephritis (especially in infancy) are described.