Recurrence and increased proliferation rate of a solitary fibrous tumor in the central nervous system--case report and review of the literature.

Meningeal solitary fibrous tumors (SFTs) were at first estimated as rare benign tumors which can be cured by total resection. To date, only 37 patients with intracranial SFTs have been reported. Therefore, the natural history of this tumor entity needs more enlightenment. The authors report a case of a 77-year-old female in whom a SFT with infiltration of the transversal sinus was subtotally resected. After a short time, interval tumor recurrence was seen, 2 years and 6 months later second surgery was performed. Immunohistologically, in both specimens typical features for SFT with positivity for CD34, vimentin and BCL-2 and negative for epithelial membrane antigen was seen. No signs for malignancy occurred in the second resection. Notably the MIB-1 index increased from 1 to 5%. In conclusion, consequent long-time follow-up for SFTs are necessary, especially after incomplete tumor resection.

[Lymphoproliferative disease following kidney transplantation]. / Lymphoproliferative Erkrankungen nach Nierentransplantation.

HISTORY AND CLINICAL FINDINGS: A 31-year-old male patient was referred because of a worsening graft function 56 months after an allogenic kidney transplantation for interstitial nephritis. He had complained about diffuse abdominal pain and watery diarrhea during the preceding week. Correction of volume status did not result in an improvement of kidney function. Bacterial or viral enteritis could be excluded as well as a mucosa-associated lymphatic tissue lymphoma (MALT-lymphoma). Shortly thereafter, the patient developed a subileus. INVESTIGATIONS: Kidney biopsy showed a low degree nephrosclerosis and some interstitial fibrosis, but no signs of rejection. The abdominal CT scan showed enlarged lymph nodes partially obstructing the intestinal lumen. Histology showed an EBV-negative, highly aggressive B-blastic lymphoma. DIAGNOSIS: EBV-negative post-transplant lymphoproliferative disease (PTLD). TREATMENT AND COURSE: Because of the advanced lymphoma stage immunosuppressive therapy was reduced and immunochemotherapy according to the CHOP-protocol (cyclophosphamide, doxorubicin, vincristine, prednisone) in combination with rituximab (R-CHOP) was started. After 4 chemotherapy cycles the patient was in complete remission and another 2 therapy cycles were given for consolidation. The patient remained free of disease during the actual follow-up of 8 months. CONCLUSION: PTLD can present with unspecific abdominal symptoms including diarrhea and with signs of graft dysfunction.

Endotoxin priming of the cyclooxygenase-2-thromboxane axis in isolated rat lungs.

Enhanced prostanoid generation has been implicated in vascular abnormalities occurring during endotoxemia and sepsis, and the lung is particularly prone to such events. Prostanoids are generated from arachidonic acid (AA) via cyclooxygenase (COX)-1 or -2, both isoenzymes recently demonstrated to be expressed in different lung cell types. Upregulation of COX may underlie the phenomenon that endotoxin [lipopolysaccharide (LPS)]-exposed lungs show markedly enhanced vasoconstrictor responses to secondarily applied stimuli (priming). Isolated rat lungs were perfused with a physiological salt buffer solution in the absence and presence of 1.5% rat plasma and exposed to different concentrations of LPS (1,000 or 10,000 ng/ml) during a 2-h priming period. No change in physiological variables was noted during this period, although enhanced baseline liberation of both thromboxane (Tx) A(2) and PGI(2) as well as of tumor necrosis factor (TNF)-alpha was evident compared with that in control lungs in the absence of LPS. LPS priming caused a significant elevation in AA-induced pulmonary arterial pressure, ventilation pressure, and lung weight gain. Concomitant increased levels of TxA(2) were found in the buffer perfusate. All changes were largely suppressed by three selective, structurally unrelated COX-2 inhibitors (NS-398, DUP-697, and SC-236) in both buffer- and buffer-plasma-perfused lungs. Anti-TNF-alpha neutralizing antibodies were ineffective under conditions of buffer perfusion. In the presence of plasma components, manyfold augmented TNF-alpha generation was noted, and anti-TNF-alpha antibodies significantly suppressed the increase in ventilation pressure but not in the vascular pressor response and lung edema formation. We conclude that the propensity of LPS-primed lungs to respond with enhanced vasoconstriction, edema formation, and bronchoconstriction to a secondarily applied stimulus proceeds nearly exclusively via COX-2 and increased Tx formation, with TNF-alpha generation being involved in the change in bronchomotor reactivity in the presence of plasma constituents. In context with recent immunohistological investigations, LPS-induced upregulation of the COX-2-thromboxane synthase axis in vascular and bronchial smooth muscle cells is suggested to underlie these events.

Identification of a penta- and hexapeptide of islet amyloid polypeptide (IAPP) with amyloidogenic and cytotoxic properties.

Pancreatic amyloid is found in more than 95 % of type II diabetes patients. Pancreatic amyloid is formed by the aggregation of islet amyloid polypeptide (hIAPP or amylin), which is a 37-residue peptide. Because pancreatic amyloid is cytotoxic, it is believed that its formation is directly associated with the development of the disease. We recently showed that hIAPP amyloid formation follows the nucleation-dependent polymerization mechanism and proceeds via a conformational transition of soluble hIAPP into aggregated beta-sheets. Here, we report that the penta- and hexapeptide sequences, hIAPP(23-27) (FGAIL) and hIAPP(22-27) (NFGAIL) of hIAPP are sufficient for the formation of beta-sheet-containing amyloid fibrils. Although these two peptides differ by only one amino acid residue, they aggregate into completely different fibrillar assemblies. hIAPP(23-27) (FGAIL) fibrils self-assemble laterally into unusually broad ribbons, whereas hIAPP(22-27) (NFGAIL) fibrils coil around each other in a typical amyloid fibril morphology. hIAPP(20-27) (SNNFGAIL) also aggregates into beta-sheet-containing fibrils, whereas no amyloidogenicity is found for hIAPP(24-27) (GAIL), indicating that hIAPP(23-27) (FGAIL) is the shortest fibrillogenic sequence of hIAPP. Insoluble amyloid formation by the partial hIAPP sequences followed kinetics that were consistent with a nucleation-dependent polymerization mechanism. hIAPP(22-27) (NFGAIL), hIAPP(20-27) (SNNFGAIL), and also the known fibrillogenic sequence, hIAPP(20-29) (SNNFGAILSS) exhibited significantly lower kinetic and thermodynamic solubilities than the pentapeptide hIAPP(23-27) (FGAIL). Fibrils formed by all short peptide sequences and also by hIAPP(20-29) were cytotoxic towards the pancreatic cell line RIN5fm, whereas no cytotoxicity was observed for the soluble form of the peptides, a notion that is consistent with hIAPP cytotoxicity. Our results suggest that a penta- and hexapeptide sequence of an appropriate amino acid composition can be sufficient for beta-sheet and amyloid fibril formation and cytotoxicity and may assist in the rational design of inhibitors of pancreatic amyloid formation or other amyloidosis-related diseases.

Detection of multiple vascular endothelial growth factor splice isoforms in single glomerular podocytes.

Glomerular podocytes are major determinants of filtration permselectivity in the glomerulus. Although the molecular mechanisms determining the characteristics of the glomerular filtration unit are incompletely understood, vascular endothelial growth factor (VEGF) has been implicated. To analyze this process in situ, we established a method that allows exploration of in vivo mRNA expression of podocytes using single-cell reverse transcriptase-polymerase chain reaction (RT-PCR). Microdissected mouse glomeruli were held in a patch-clamp apparatus, and single podocytes were harvested by aspiration. After lysis, the cells were reverse transcribed, and PCR was performed (45 cycles). The podocyte nature of the material was confirmed by detection of podocyte-specific mRNA (glomerular epithelial protein 1 and Wilms' tumor protein 1). Using specific oligonucleotide primers, VEGF was detected in mRNA obtained from renal cortex, single microdissected glomeruli, cultured murine podocytes, and single podocytes in situ. All cells examined expressed three VEGF isoforms (121, 165, and 189). These differ in their capacity for binding to extracellular matrix and could have different potencies regulating glomerular endothelial permeability. Our approach should allow a semiquantitative, isoform-specific evaluation of VEGF mRNA expression in podocytes during nephrogenesis and in glomerular disease.

Loss of lifetime due to radiation exposure-averaging problems.

A new method is presented for assessing a years of life lost (YLL) due to stochastic effects caused by the exposure to ionizing radiation. The widely accepted method from the literature uses a ratio of means of two quantities, defining in fact the loss of life as a derived quantity. We start from the real stochastic nature of the quantity (YLL), which enables us to obtain its mean values in a consistent way, using the standard averaging procedures, based on the corresponding joint probability density functions needed in this problem. Our method is mathematically different and produces lower values of average YLL. In this paper we also found certain similarities with the concept of loss of life expectancy among exposure induced deaths (LLE-EID), which is accepted in the recently published UNSCEAR report, where the same quantity is defined as years of life lost per radiation induced case (YLC). Using the same data base, the YLL and the LLE-EID are calculated and compared for the simplest exposure case-the discrete exposure at age a. It is found that LLE-EID overestimates the YLL, and that the magnitude of this overestimation reaches more than 15%, which depends on the effect under consideration.

How much brushing is enough for the diagnosis of lung tumors?

BACKGROUND: Bronchoscopic investigations of lung tumors require high diagnostic accuracy. Sometimes the combination of brush biopsy with cytologic and histologic examination of forceps-obtained biopsy specimens fails to diagnose tumors. Techniques with a minimum risk and low cost when repeated several times could increase the efficiency of tumor diagnosis and help to avoid rebronchoscopy. METHODS: Repeated brush biopsies were done during one bronchoscopic examination in 270 patients with pulmonary neoplasias using a flexible fiberoptic bronchoscope guided by radiographic video fluoroscopy. The results of up to five brush biopsies were compared for their diagnostic sensitivity. RESULTS: Singly, 68-77% of the specimens showed malignant findings. With repeated brushing, the sensitivity of the diagnostic accuracy increased to 89.6%. In the periphery of the bronchial tree, the sensitivity of brush biopsy was slightly lower in bronchoscopically invisible tumors. In 222 of 242 (91.7%) patients with positive results of brush biopsy, there was agreement in the final typing of tumor morphology. CONCLUSION: For routine bronchoscopy, repeated brush biopsy should be done to obtain the highest diagnostic yield.

Ct air-contrast scanning of the internal auditory canal.

Two hundred and four patients with audiometric and vestibular findings suggestive of a retrocochlear lesion were studied prospectively by computed tomographic scan with air contrast of the internal auditory canal. With this technique tumor limits are clearly defined. In the absence of disease the internal auditory canal has been completely air-filled in over 97% of cases. Soft tissue masses occluding the internal auditory canal were demonstrated in 11 patients. Four studies were inconclusive and there was one false positive. Headaches have been the only side effect and there have been no complications. In reporting their results the authors examined the indications, accuracy and limitations of this technique. This study demonstrates that computed tomographic scan with air contrast of the internal auditory canal should be considered as the radiologic procedure of choice for the evaluation of small acoustic tumors.

Ultrahigh-frequency electromagnetic fields for weed control: phytotoxicity and selectivity.

An ultrahigh-frequency electromagnetic field (2450+/-20 megahertz) is lethal to plants and seeds of several species after relatively short exposure times. Some species are highly susceptible; others are relatively resistant to a given field intensity. Phytotoxicity is increased in imbibed seeds and young plants. It is decreased in dry seeds and sometimes decreased in mature plants. Soil partially attenuates the field but is not opaque to it.