Chemogenetic ON and OFF switches for RNA virus replication.

Therapeutic application of RNA viruses as oncolytic agents or gene vectors requires a tight control of virus activity if toxicity is a concern. Here we present a regulator switch for RNA viruses using a conditional protease approach, in which the function of at least one viral protein essential for transcription and replication is linked to autocatalytical, exogenous human immunodeficiency virus (HIV) protease activity. Virus activity can be en- or disabled by various HIV protease inhibitors. Incorporating the HIV protease dimer in the genome of vesicular stomatitis virus (VSV) into the open reading frame of either the P- or L-protein resulted in an ON switch. Here, virus activity depends on co-application of protease inhibitor in a dose-dependent manner. Conversely, an N-terminal VSV polymerase tag with the HIV protease dimer constitutes an OFF switch, as application of protease inhibitor stops virus activity. This technology may also be applicable to other potentially therapeutic RNA viruses.

Molecular evidence that human ocular ciliary epithelium expresses components involved in phototransduction.

Here we report the expression, in the human ocular ciliary epithelium and in a human nonpigmented (NPE) ciliary epithelial cell line, of genes usually restricted to cone and rod photoreceptor cells of the retina. By RT-PCR and DNA sequencing we identified the expression of rhodopsin and components linked to its deactivation, including rhodopsin kinase, recoverin, and visual arrestin. We also detected the expression of transducin (T-alpha), phosphodiesterase (PDE-alpha), and cGMP-gated channel alpha-subunits. Cultured NPE cells responded to treatment with phorbol ester by enhancing the expression of rhodopsin mRNA three- to fourfold. Indirect immunofluorescence of the intact ciliary epithelium with monoclonal antibodies (MAbs) against rhodopsin, rhodopsin kinase, and visual arrestin revealed labeling preferentially restricted to the NPE cells. Furthermore, Western blot analysis of whole lysates from the pars plicata region of the human ciliary epithelium with MAbs demonstrated immunochemical cross-reactivity with proteins of molecular mass similar to rhodopsin (36 kDa), rhodopsin kinase (64 to 66 kDa), and arrestin (48-52 kDa) from the human retina. These results provide the first molecular evidence that components of a non-visual phototransduction pathway are expressed in the human ocular NPE ciliary epithelium, which may be linked to circadian entrainment tasks.

[Surgical treatment of para-articular ossifications after craniocerebral trauma]. / Zur operativen Behandlung von Paraartikulären Ossifikationen nach Schädel-Hirn-Traumen.

This article reports on 45 cases in which extra-articular ossifications were removed following cranial-cerebral traumata. Radiologically detectable relapses occurred in 6% of the patients only; however, in none of these cases did the relapses lead to reankylosis of the joint. In the sagittal plane, the average gain in mobility was an increase of 84 degrees in the hip joint and of 100 degrees in the elbow joint. Considerable complications were caused by four fractures in extremely osteoporotic bones. To reduce the fracture rate, surgery should be performed as soon as possible after bone maturation. In addition, treatment of patients with craniocerebral traumata and serious concomitant conditions requires an experienced rehabilitation team.

[Concentrations and levels of activity of important serum protein components in preserved serum]. / Konzentrations- und Aktivitätsmessungen wichtiger Serumproteinanteile in Serumkonserven.

The content of transport proteins, immune globulins, components of the complement system and protease inhibitors were estimated in two different plasma preparations, using bioassays by chromogenic substrates and laser nephelometry. The content of proteins under consideration was found about 50% less than in untreated human plasma. Some proteins such as antithrombin III and factor XIII are missing. The results are discussed in respect to clinical used of plasma preparations.

[Ultrasonic diagnosis of ovarian tumours (author's transl)]. / Ultraschalldiagnostik von Adnextumoren.

Precise knowledge of the echoanatomy of the normal female pelvis is a prerequisite in the diagnosis of ovarian tumours. Diagnostic criteria for the differentiation between cystic and solid lesions are discussed. The echographic appearance of uni-, multilocular, dermoid and endometriosis cysts and of ovarian cancer is described. 183 ovarian tumours were examined in the period from January 1st, 1976 until December 31st, 1977 and the preoperative diagnosis compared with the findings at operation, both macroscopic and histological. 158 cases (86.3%) were correctly diagnosed. In 13 cases (7.1%) the diagnosis was only partially correct. An incorrect ultrasonic diagnosis was made in only 12 cases (6.6%). Out of 183 cases the side of the lesion was correctly diagnosed in 128 patients (70.0%). Localization of the tumour could not be achieved or was totally wrong in 19 cases (10.4%). Estimated tumour dimensions concurred with the macroscopic measurements of the specimen in 90.7%. A false-positive result was recorded in 7 cases (3.8%), mostly due to a full bowel simulating a cyst of barely 4 cm in diameter. In 5 cases (2.7%) ultrasonic examination failed to detect the existence of a tumour. 2 of these tumours were follicular cysts under 4 cm in diameter. 2 ovarian cancers were missed. In 1 case the ovary was only slightly enlarged and the diagnosis was made only by frozen-section histology. In the second case the tumour was erroneously interpreted as originating from the sigmoid colon. Ultrasonic diagnosis is recommended for the detection and differentiation of ovarian tumours on the basis of the good results achieved.