[Melanosis of the urinary bladder]. / Melanose der Harnblase.

Melanosis of the bladder is rare. Only 10 cases have been described in the literature. We present the case of an 80-year-old woman with neurogenic lower urinary tract dysfunction due to spinal paralysis. During the diagnostic work-up which included cystoscopy, black spots in the bladder wall were observed. Histopathological evaluation revealed a benign suburothelial melanosis. Thus, with cystoscopic suspicion of a malignancy (melanoma), a biopsy is mandatory and regular cystoscopic follow-up is recommended.

[Squamous cell carcinoma of the bladder in a patient with HIV and paraplegia]. / Plattenepithelkarzinom der Harnblase bei einem Patienten mit HIV und Paraplegie.

In patients with spinal cord injury (SCI) the rate of squamous cell carcinomas (SCC) among bladder tumors is increased compared to the general population. An increased life expectancy is achieved by modern HIV treatment so that more AIDS-unrelated malignomas, e.g. bladder tumors, occur in these patients. Therefore, the risk for SCC in this group of patients is increased in patients with SCI and HIV but the combination of these two diseases is rare. We report the first case of SCC in a patient with SCI and HIV. Initial symptoms of bladder tumors in patients with SCI are often unspecific; therefore, in cases with new onset hematuria, recurrent urinary tract infections and changes in bladder function, cystoscopy and computed tomography (CT) scanning should be considered.

[Psammomatous tenosynovialitis of hand and forearm - three new cases]. / Psammomatöse Tenosynovialitis an Hand und Unterarm - drei neue Fälle.

We report about three new observations of psammomatous tenosynovialitis on hand and forearm and performed a review of literature. To the best of our knowledge cases 7, 8 and 9 in the medical literature are now published.

Postoperative determination of the degree of carotid artery stenosis / Determinação pós-operatória do grau de estenose na artéria carótida

This article describes the VascMorph 1a prototype software and reports first results obtained with postoperative determination of the degree of stenosis in the carotid artery.

Este artigo descreve o programa protótipo VascMorph 1a e apresenta os primeiros resultados obtidos com a determinação pós-operatória do grau de estenose na artéria carótida.

[Recurrence of a tendon sheath tumor on the hand consisting of three morphological components]. / Rezidivierender Sehnenscheidentumor der Hand bestehend aus drei morphologischen Komponenten.

We report of a benign, recurrent tendon sheath tumour. Histologically, three different morphological components were observed.

[Ascending aortic and pulmonary trunk aneurysms]. / Aneurysmata der Aorta ascendens und des Truncus pulmonalis.

A case of two non-atherosclerotic aneurysms localised in the ascending aorta and in the pulmonary trunk is presented. Histopathologically, a severe granulomatous inflammation affecting the whole aneurysms wall was documented. To the best of our knowledge it is the second ever documented case of simultaneous occurrence of aneurysms in the aorta and the pulmonary artery.

ABIN-2 forms a ternary complex with TPL-2 and NF-kappa B1 p105 and is essential for TPL-2 protein stability.

NF-kappa B1 p105 forms a high-affinity, stoichiometric interaction with TPL-2, a MEK kinase essential for TLR4 activation of the ERK mitogen-activated protein kinase cascade in lipopolysaccharide (LPS)-stimulated macrophages. Interaction with p105 is required to maintain TPL-2 metabolic stability and also negatively regulates TPL-2 MEK kinase activity. Here, affinity purification identified A20-binding inhibitor of NF-kappa B 2 (ABIN-2) as a novel p105-associated protein. Cotransfection experiments demonstrated that ABIN-2 could interact with TPL-2 in addition to p105 but preferentially formed a ternary complex with both proteins. Consistently, in unstimulated bone marrow-derived macrophages (BMDMs), a substantial fraction of endogenous ABIN-2 was associated with both p105 and TPL-2. Although the majority of TPL-2 in these cells was complexed with ABIN-2, the pool of TPL-2 which could activate MEK after LPS stimulation was not, and LPS activation of TPL-2 was found to correlate with its release from ABIN-2. Depletion of ABIN-2 by RNA interference dramatically reduced steady-state levels of TPL-2 protein without affecting levels of TPL-2 mRNA or p105 protein. In addition, ABIN-2 increased the half-life of cotransfected TPL-2. Thus, optimal TPL-2 stability in vivo requires interaction with ABIN-2 as well as p105. Together, these data raise the possibility that ABIN-2 functions in the TLR4 signaling pathway which regulates TPL-2 activation.

Takayasu's arteritis secondary to myelodysplasia as a predictor of poor outcome: two case reports.

We present two patients with myelodysplasia in association with Takayasu's arteritis (TA). In both patients intensive immunosuppressive treatment could not control the vascular inflammation. Subsequently both patients developed myelodysplasia, rapidly progressing to secondary acute myelogenous leukaemia. One patient had a peripheral blood stem cell transplant from a compatible sibling donor, but died of refractory leukaemia 5 months later. The other patient died of fungal sepsis. These are the first two patients reported to have TA associated with myelodysplasia/secondary leukaemia.

Fibromuscular dysplasia of the renal artery responsible for renovascular hypertension: a histological presentation based on a series of 102 patients.

BACKGROUND: Fibromuscular dysplasia (FMD) is a rare non-atherosclerotic and non-inflammatory disease in the arterial system. The purpose of the study was a retrospective analysis of FMD in the renal artery. PATIENTS AND METHODS: A total number of 102 patients (mean age: 36.9 years) who suffered from renovascular hypertension underwent a surgical therapy. The operative specimens of the renal arteries were analysed with the lightmicroscop using histological and immunohistochemical methods. RESULTS: 101 patients (99.02%) presented a medial FMD (extensive-medial subtype in 56 patients, 54.9%, subadventitial subtype in 29 patients, 28.4% and combined subtype in 16 patients, 15.7%). In 1 patient (0.98%) an adventitial FMD was found. We observed the following complications: true and dissecting aneurysms (75 patients, 74.5%), arterio-venous fistulae (2 patients, 1.96%) and chronic thrombosis (10 patients, 9.8%). CONCLUSIONS: With the progress in angioplasty, not all patients suffering from FMD undergo a primary surgical therapy and therefore this lesion is less seen in the daily work of the histopathologist.

[Radiologic-histopathologic correlation of microcalcifications from 11g vacuum biopsy: analysis of 3196 core biopsies]. / Radiologisch-histopathologische Korrelation von Mikrokalzifikationen in 11-G-Vakuumbiopsaten - eine Analyse von insgesamt 3196 Proben.

PURPOSE: To perform a statistical evaluation of microcalcifications (MC) from suspicious breast lesions detected by radiography and histopathology. MATERIALS AND METHODS: Histological and radiological detection of calcifications were compared from 116 biopsies in 96 women. Lesions with identical description of calcifications detected in histopathology and radiography were considered concordant, patients with obvious discrepancies discordant. If histological and radiological groups of calcifications were identical in number but differed in location, the case was considered pseudo-concordant. RESULTS: Histopathology classified 24 of 116 lesions as malignant and 92 as benign. A total of 3196 core biopsies were examined, 851 of these contained groups of calcifications or single calcifications. Both modalities detected 579 calcifications, with 169 exclusively detected by radiography and 103 exclusively by histopathology. In 35 cases (30 %) radiologic and pathologic results were concordant, in 6 cases pseudo-concordant (4 %) and in 75 cases (65 %) discordant. The case-based Kappa coefficient was - 0.09 (- 0.24 to 0.07). The 122 calcifications not detected by histopathology were few or single calcifications at the edge of the core that were probably lost during processing, 18 were possible artefacts. Six cores contained calcium oxalate, 3 contained milk of calcium. In 6 cases malignant disease was found after the first examination, hence the cores were not searched thoroughly for the missing calcifications. In the remaining 14 cases, no calcifications were found despite complete processing of the tissue. In 49 of 103 cases of radiologically undetected microcalcifications, the retrospect analysis showed dense tissue areas that probably contained the calcification. The remaining 54 cases contained calcifications, which were too small to be detected radiologically. SUMMARY: Discordant results from pathological and radiological examinations of biopsies can mainly be explained by calcifications at the edge of the specimen lost during processing, which are therefore not detected in histopathology, and calcifications too small to be visualized radiologically.

Intrathoracic and intraabdominal locations of a cystic benign tumor: congenital etiology due to embryological diaphragm development?

A rare case of a benign cystic two-cavity tumor with intrathoracic and intraabdominal localisation is presented. The tumor's embryological etiology, embryological development of the diaphragm and the occurrence of embryonic tumors in general, are discussed. To our knowledge this is the first documented case of a benign two-cavity tumor in childhood and infancy.

Sebaceous glands in the uterine cervix: two new cases.

The authors report on two new cases of sebaceous glands in the uterine cervix. This extremely rare histological observation was found on biopsy specimens of the uterine cervix because of unclear colposcopic findings and of recurrent CIN II. The etiology of this entity is discussed including a brief review of the medical literature.

CD40 regulates the processing of NF-kappaB2 p100 to p52.

The nf-kb2 gene encodes the cytoplasmic NF-kappaB inhibitory protein p100 from which the active p52 NF-kappaB subunit is derived by proteasome-mediated proteolysis. Ligands which stimulate p100 processing to p52 have not been defined. Here, ligation of CD40 on transfected 293 cells is shown to trigger p52 production by stimulating p100 ubiquitylation and subsequent proteasome-mediated proteolysis. CD40-mediated p52 accumulation is dependent on de novo protein synthesis and triggers p52 translocation into the nucleus to generate active NF-kappaB dimers. Endogenous CD40 ligation on primary murine splenic B cells also stimulates p100 processing, which results in the delayed nuclear translocation of p52-RelB dimers. In both 293 cells and primary splenic B cells, the ability of CD40 to trigger p100 processing requires functional NF-kappaB-inducing kinase (NIK). In contrast, NIK activity is not required for CD40 to stimulate the degradation of IkappaBalpha in either cell type. The regulation of p100 processing by CD40 is likely to be important for the transcriptional regulation of CD40 target genes in adaptive immune responses.

Urinary bladder biopsies in spinal cord injured patients.

STUDY DESIGN: A series of 94 urinary bladder biopsies in spinal cord injured (SCI) patients were histopathologically and statistically analysed. OBJECTIVES: The following hypotheses were examined: (1) The number of clinical bladder infections per year in each patient does not influence the histopathological type of inflammation of the urinary bladder; (2) The duration of the spinal cord lesion does not have a strong effect on the type of inflammation; (3) The different neurological levels (upper and lower motor neuron lesions) do not relate to a specific histopathology. SETTINGS: All patients received their treatment at the Swiss Paraplegic Centre in Nottwil, near Lucerne (Switzerland). METHODS: The samples were taken from the bladder fundus during endoscopic urologic operations. Histopathological standard procedures were carried out. Statistical analysis including Kruskal-Wallis and Chi-square tests were performed. RESULTS: Histopathological analysis showed abnormal alterations of the urinary bladder mucosa in 86 SCI-patients: (91.5%). 63 cases (67.0%) showed a chronic type and 23 cases (24.5%) showed a subacute type of inflammation. A normal urinary bladder was found in eight cases (8.5%). The three hypotheses were statistically not rejected. CONCLUSION: Results demonstrated no correlation between the number of bladder infections per year, the period since injury, the neurologic level of the spinal cord lesion and the histopathology of the urinary bladder mucosa.

Arterial calcifications: morphological aspects and their pathological implications.

Morphological aspects of calcifications are identical whatever their site in the arterial layers: fine granular deposits, plates, rings. Occurrence of complications: fibrosis with foreign body type granuloma, thrombosis, and embolism mainly depend on the site and the amount of calcification. Clinicians should be aware of these complications when performing angioplasty.

Direct phosphorylation of NF-kappaB1 p105 by the IkappaB kinase complex on serine 927 is essential for signal-induced p105 proteolysis.

The p105 precursor protein of NF-kappaB1 acts as an NF-kappaB inhibitory protein, retaining associated Rel subunits in the cytoplasm of unstimulated cells. Tumor necrosis factor alpha (TNFalpha) and interleukin-1alpha (IL-1alpha) stimulate p105 degradation, releasing associated Rel subunits to translocate into the nucleus. By using knockout embryonic fibroblasts, it was first established that the IkappaB kinase (IKK) complex is essential for these pro-inflammatory cytokines to trigger efficiently p105 degradation. The p105 PEST domain contains a motif (Asp-Ser(927)-Gly-Val-Glu-Thr), related to the IKK target sequence in IkappaBalpha, which is conserved between human, mouse, rat, and chicken p105. Analysis of a panel of human p105 mutants in which serine/threonine residues within and adjacent to this motif were individually changed to alanine established that only serine 927 is essential for p105 proteolysis triggered by IKK2 overexpression. This residue is also required for TNFalpha and IL-1alpha to stimulate p105 degradation. By using a specific anti-phosphopeptide antibody, it was confirmed that IKK2 overexpression induces serine 927 phosphorylation of co-transfected p105 and that endogenous p105 is also rapidly phosphorylated on this residue after TNFalpha or IL-1alpha stimulation. In vitro kinase assays with purified proteins demonstrated that both IKK1 and IKK2 can directly phosphorylate p105 on serine 927. Together these experiments indicate that the IKK complex regulates the signal-induced proteolysis of NF-kappaB1 p105 by direct phosphorylation of serine 927 in its PEST domain.

Cholesterol depletion disrupts lipid rafts and modulates the activity of multiple signaling pathways in T lymphocytes.

Lipid rafts are specialized plasma membrane microdomains, in which glycosphingolipids and cholesterol are major structural components. In T lymphocytes, several signaling proteins are associated with lipid rafts including the protein tyrosine kinase LCK and the adapter protein LAT. To investigate their importance in T cell signaling, lipid rafts were disrupted by depleting cholesterol with methyl-beta-cyclodextrin (MbetaCD). This transiently induced tyrosine phosphorylation of multiple proteins, including the ZAP-70 tyrosine kinase, its associated T cell antigen receptor zeta chain, LAT and phospholipase Cgamma1. Tyrosine phosphorylation was dependent on expression of LCK in lipid rafts. Depletion of cholesterol also resulted in activation of the Ras-ERK pathway. This was largely dependent on phorbol ester-sensitive protein kinase C (PKC) and the PKC-theta isoform translocated to the plasma membrane following MbetaCD treatment. MbetaCD did not stimulate intracellular Ca2+ fluxes; however, consistent with its ability to stimulate Ras, MbetaCD synergized with a Ca2+ ionophore to induce formation of the transcription factor NF-AT. These data indicate a crucial role for cholesterol in the regulation of signaling pathways in T cells, which is likely to reflect its importance in the formation of plasma membrane lipid rafts.