A role for MALT1 activity in Kaposi's sarcoma-associated herpes virus latency and growth of primary effusion lymphoma.

Primary effusion lymphoma (PEL) is an incurable malignancy that develops in immunodeficient patients as a consequence of latent infection of B-cells with Kaposi's sarcoma-associated herpes virus (KSHV). Malignant growth of KSHV-infected B cells requires the activity of the transcription factor nuclear factor (NF)-κB, which controls maintenance of viral latency and suppression of the viral lytic program. Here we show that the KSHV proteins K13 and K15 promote NF-κB activation via the protease mucosa-associated lymphoid tissue lymphoma translocation protein-1 (MALT1), a key driver of NF-κB activation in lymphocytes. Inhibition of the MALT1 protease activity induced a switch from the latent to the lytic stage of viral infection, and led to reduced growth and survival of PEL cell lines in vitro and in a xenograft model. These results demonstrate a key role for the proteolytic activity of MALT1 in PEL, and provide a rationale for the pharmacological targeting of MALT1 in PEL therapy.

Early detection of hepatitis B surface antigen--prototype of a new fully automated HBsAg microparticle enzyme immunoassay (MEIA).

HBsAg is the most important serological marker of acute and chronic hepatitis B infection. Therefore, sensitivity of the currently used detection systems for HBsAg is of major importance for blood screening, diagnosis of HBV infection and therapy monitoring of HBV infected individuals. A Prototype Microparticle Enzyme Immunoassay (MEIA) for qualitative determination of hepatitis B surface antigen (HBsAg) has recently been developed for the fully automated AxSYM analyzer with the intention to provide a test displaying improved sensitivity when compared to the currently marketed HBsAg assays. The present study was conducted to demonstrate sensitivity of the new Prototype AxSYM HBsAg MEIA and the corresponding, fully automated Prototype AxSYM HBsAg Confirmatory MEIA. Analytical sensitivity of the Prototype AxSYM HBsAg MEIA was assessed by testing quantitative HBsAg panels. Sensitivity for HBsAg subtypes ad and ay was found to be 0.15 ng/ml and 0.09 ng/ml, respectively. The detection level for HBsAg subtype ad Standard provided by the Paul Ehrlich Institute was estimated to be 0.03 PEI U/ml. Analysis of hepatitis B seroconversion panels suggests that the new Prototype AxSYM HBsAg MEIA significantly reduces the seroconversion window when being compared to other highly sensitive commercial HBsAg assays. The corresponding Prototype AxSYM HBsAg Confirmatory MEIA demonstrated the ability to confirm low titer seroconverters found reactive with the Prototype AxSYM HBsAg Screening MEIA.

"Ring fixator" for treatment of lower leg fractures. A review of 30 cases treated by a new external fixation system.

Besides generally known therapeutic practice, indications can be discovered and more easily evaluated by using a "Ring Fixator". Applications include the following: (1) stage fractures of the tibia, (2) stabilisation of fractures of polytraumatized patients with no need for prior anatomical reduction and (3) closed lower limb fractures with severe soft tissue lesions. The major advantages of the "Ring Fixator" include the following: possible unlimited correction of primary and secondary dislocations without needing to transpose implanted Steinmann-pins or Schanz' screw; compatibility with ASIF external fixation systems for supplementary use of "Ring Fixator" elements; possible management of secondary dislocations and variable placement of pins or screws for subsequent wound debridement and muscle flap transposition. Results so far obtained using the "Ring Fixation" are illustrated by clinical examples.

[Severe chronic headache with depression induced by pachymeningitis in Wegener's granulomatosis]. / Chronischer Kopfschmerz mit Depression durch Pachymeningitis bei Wegener-Granulomatose.

HISTORY AND ADMISSION FINDINGS: A 43-year-old man was admitted to a hospital because of an exacerbation of severe headache, which for three years had been refractory to any treatment. Headache had led to chronic use of analgesics and to drug-treated depression. As a result he had to quit his job the previous year and had since then been receiving a disability pension. At that time diagnostic procedures done elsewhere, including cranial computer tomography and laboratory tests had not shown any pathological results. At the current admission the patient was in a reduced general condition and complained of severe headache and depression. However, the physical examination, including neurological tests, was normal. INVESTIGATIONS: Cranial magnetic resonance imaging (MRI) revealed general thickening and pronounced contrast enhancement of all meningeal structures (pachymeningitis). Laboratory tests indicated renal failure and proteinuria, as well as elevation of anti-neutrophilic cytoplasmic antibodies against proteinase 3 (PR3-ANCA). DIAGNOSIS, TREATMENT AND COURSE: The MRI findings and laboratory results established the diagnosis of a severe pachymeningitis secondary to vasculitis of the central nervous system as part of Wegener's granulomatosis. Immunosuppressive therapy with cyclophosphamide and glucocorticoids resulted in the severe headaches subsiding within a few days. The patient was able to stop taking analgesics and antidepressants. However, renal function improved only partially. CONCLUSION: Pachymeningitis, as demonstrated on MRI, is a rare manifestation of inflammatory cerebrovascular involvement in Wegener's granulomatosis. Pachymeningitis should be considered in patients with severe and persistent headache of unknown aetiology, as well as in patients with Wegener's granulomatosis with recent onset of headache.

Identification of human red cell glutamate-pyruvate transaminase (GPT) phenotypes by isoelectric focusing.

Isoenzymes of human red cell glutamate-pyruvate transaminase (GPT) were resolved by isoelectric focusing (IEF) of hemolysates in polyacrylamide gels at pH 5.0-7.0. The bands of enzyme activity required both alpha-ketoglutarate and L-alanine in the staining mixture for visualization, indicating that the bands were not lactate dehydrogenase or glutamate dehydrogenase. Phenotyping of 41 individuals by IEF, including types GPT 1, 2A, 1-2A, 1-2B, and 2A-2B, agreed with the typing results obtained by electrophoresis in starch gels and in polyacrylamide gels at acid and alkaline pH. Analysis of one kindred demonstrated autosomal codominant transmission of the rare GPT*2B gene through 3 generations. IEF facilitates phenotyping by permitting identification of the GPT types on a single gel with a considerable reduction in time and cost. Although no new variants were found in this investigation, IEF may be more powerful for the recognition of presently undetected variants of GPT.

[The external ring fixation--experimental studies of bending stability in distraction osteosyntheses]. / Der Ringfixateur externe--Experimentelle Untersuchungen zur Biegestabilität bei Distanzosteosynthesen.

There is a high axial load for lower leg distractive osteosyntheses with external fixation systems. In searching for a high rigidity comparative investigations on the stability with different external fixators were carried out by an own-developed material testing machine. Our anular fixator showed more rigidity than a three-dimensional ASIF-external fixateur. The use for infected fractures by changing the treatment, pseudarthrosis and also distractive osteosyntheses with weight bearing (for example Ilisarov-method) is possible.

[Treatment of tibial fractures with external ring fixation--I]. / Die Behandlung von Unterschenkelfrakturen mit dem Ringfixateur externe--Teil I.

Notwithstanding the generally known principles of therapy, indications can be enlarged by use of an annular fixator to cover the following applications: 1. stage fractures of the tibia, 2. stabilisation of fractures of polytraumatised patients with no need for anatomic reposition in the first place, 3. closed lower limb fractures with soft tissue lesions. Possible unlimited correction of primary and secondary dislocations without the need for transposition of Steinmann pins already implanted, compatibility with AO external fixation systems for supplementary use of annular fixator elements for possible management of secondary dislocations and variable placeability of pins or screws for subsequent wound debridement and muscle flap transposition are major advantages of the annular fixator. Results so far obtained from use of the annular fixator are described by clinical examples.

[Transfixation method--treatment of tibial fracture with external ring fixation--II]. / Die Transfixationsmethode--Behandlung von Unterschenkelfrakturen mit dem Ringfixateur externe--Teil II.

The transfixation method first introduced by Böhler has been modified by means of a self-devised annular fixator and has thus been re-introduced by the authors of this paper, with the view to reducing the drawbacks of conservative and surgical treatment of closed lower leg fractures. Reposition of the fracture is achieved by means of this paper, with the view to reducing the drawbacks of conservative and surgical low. Retention is followed by application of a plaster cast up to the knee, with the Steinmann pins covered. Technique, indication, and results are described. Successful fracture consolidation was achieved in good position and with good functional results in all cases.