[Stress analysis of the human mandible in standard trauma situations with numerical simulation]. / Spannungsanalyse des menschlichen Unterkiefers bei traumatologischen Standardsituationen mittels numerischer Simulation.

For the stress analysis of the human mandible a flexible simulation concept basing on finite element-method has been developed. One of the main issues is the prediction of fractures as a consequence of known forces as well as the forensic reconstruction of the traumatologic situation. At first, the individual geometry was reconstructed by 3D-CT-Scans. To reduce the simulation efforts, for the time being the anisotropic structural mechanics of the jaw bone was neglected in favour of an homogeneous and isotropic material law. Assuming the Von-Mises-Stress as a failure indicator the results of the simulations were in good agreement with typical traumatologic situations. For further validation of the model, a real failure case, shown on a radiograph of a injured human mandible with three fractures, was simulated and, by this, the real incident was reconstructed. Reasonable planned extensions of the actual simulation concept have the regard on the nerve channel, the temporomandibular joint's function, the paradontal apparatus and the individual mechanical properties of the bone.

[Numerical simulation (FEM) of the human mandible: validation of the function of the masticatory muscles]. / Numerische Simulation (FEM) des menschlichen Unterkiefers: Validierung der Umsetzung der Kaumuskulatur.

The article describes part of a research project aiming to develop a new modular software tool for the individual dynamic numerical simulation of the human mandible using the finite element method (FEM). Its planned use in the clinical setting makes it very important to validate the results of the simulations. Here, the function of the masticatory muscles is to be tested. On the basis of biomechanical data from the literature, standard movements, such as closing the mouth, forward movement, lateral movement or backward movement, were dynamically simulated. Apart from muscle activity, the movements of the mandible are defined by the temporomandibular joint. At present, translating the condylar dynamics to the simulation still poses problems. For this reason, therefore, simulations of the two extreme cases "fixed" and "force-free" condyles are compared. While in the case of fixed condyles, some of the movements could be reproduced either not at all or only weakly, in the case of force-free condyles, all standard movements were reproduced qualitatively, albeit without the guiding effect of the joint capsule or the articular disc.

[A modular software concept for individual numerical simulation (FEM) of the human mandible]. / Ein modulares Software-Konzept für individuelle numerische Simulation (FEM) des menschlichen Unterkiefers.

A new modular software concept for individual numerical simulation of the human mandible using the finite element method (FEM) is presented. The main task is an individual analysis of regional stress and stress-compatibility on the basis of computed tomographic data in individual patients. Simulation should, however, also be possible in parallel with biomechanical experiments, or for further research projects. For this purpose, rapid and uncomplicated generation of the FEM model, easy modification of input data, and short computation times are required. Practical use in the clinical setting makes appreciable additional demands on the individual software components.

Cosmid cloning and restriction endonuclease mapping of the herpesvirus of turkeys (HVT) genome.

The genomic libraries of the herpesvirus of turkeys (HVT) presented to date do not include the entire genome. To construct a complete genomic library, HVT DNA was partially digested with Sau3A and inserted into the double cos site vector pcos2EMBL. The PstI maps derived from the partial Sau3A library demonstrate that the left region of the genome compared to the right area is overrepresented. Similar to the libraries of the HVT genome established earlier, a defined portion of the middle genomic region, however, is not contained in the partial Sau3A library. Cloning of HVT DNA in pcos2EMBL, employing BamHI for the partial digestion step, enabled to find the recombinant cosmid cBL267 which carries the BamHI-C and -D fragment as DNA insertion. As shown by Southern blot hybridization, the BamHI-C fragment ranges in a size to close the gap in the partial Sau3A library and thus guarantees the completeness of the genomic library of HVT which consists of seven overlapping cosmid clones (cBL1, cBL328, cBL11, cBL267, cBL27, cBL33, and cBL34).

Identification of genomic regions of the herpesvirus of turkeys (HVT) with helper activity for avian adeno-associated virus (AAAV).

Herpesvirus of turkeys (HVT) is a potent helper for the defective parvovirus avian adeno-associated virus (AAAV). To study the helper mechanism at the molecular level, we established a complete cosmid library of HVT DNA in a set of seven overlapping clones and transiently cotransfected secondary chicken embryo fibroblast (CEF) cells with AAAV DNA and recombinant cosmids (cBL) (individual as well as in different combinations). Using an AAAV-specific indirect immunofluorescence assay, we identified four regions on the HVT genome, represented by cBL267, cBL27, cBL33, and cBL34, which express helper functions for AAAV. As demonstrated by infection studies with extracts from cotransfected CEF cells, cBL267 promotes productive AAAV growth, while the helper effect induced by cBL27, cBL33, and cBL34 is limited to the synthesis of noninfectious AAAV antigen. In view of the data presented, possible HVT-specific helper mechanisms for AAAV are discussed.

Multiple sclerosis in children: cerebral metabolic alterations monitored by localized proton magnetic resonance spectroscopy in vivo.

In vivo proton magnetic resonance spectroscopy of 8 children (7-16 years) with established multiple sclerosis revealed distinct alterations in regional cerebral metabolism associated with different aspects of the disease: (1) Localized proton spectra (2 to 4-ml volumes of interest) from multiple sclerosis plaques were generally characterized by a decrease in N-acetylaspartate and creatine, and an increase in cholines and myo-inositol relative to age-matched control subjects, (2) neither chronic nor enhancing plaques (by gadolinium-diethylenetriamine pentaacetic acid) during an acute exacerbation showed elevated levels of lactate or lipids, (3) spectra from adjacent white matter that did not appear suspicious in magnetic resonance images were similar to those of normal control subjects, and (4) cortical gray matter related to neighboring multiple sclerosis lesions showed a notable reduction of N-acetylaspartate. The present results show that functional impairment in multiple sclerosis is linked to gross metabolic disturbances of neuronal cell chemistry. We suggest that focal demyelination is accompanied by increased membrane precursors of proliferative turnover and is associated with secondary neuronal shrinkage or loss, perhaps extending into related cortical gray matter.

Multiple sclerosis in childhood: report of 15 cases.

We report the preliminary results of an ongoing study of multiple sclerosis (MS) in childhood. The investigations include an analysis of the clinical picture and course. Multiple sclerosis in early childhood may present atypically, with a symptomatology suggesting diffuse encephalomyelitis, meningeal reaction, brain oedema, seizures, impaired consciousness and in some cases take a lethal course. Imaging studies including MRI and MR-spectroscopy, CSF-analysis, electrophysiology (VEP, BAEP, SER), and virological and immunological investigations are performed. So far 15 children have been studied. Their age at the onset of the disease ranged from 3 to 15 years. Abnormal CSF-findings with pleocytosis and oligoclonal IgG bands were present in 11 and 10 out of 15 patients respectively. MRI revealed numerous white matter lesions in the brain stem and cerebral hemispheres. VEP, BAEP and SER's were abnormal in most children. Proton magnetic resonance spectra from plaques exhibited a 50-80% decrease in N-acetyl aspartate, which is a potential marker of vital neuronal tissue, a decrease of the creatine pool and an increase of choline-containing compounds. Lactate was not increased. Our observations of MS in early childhood cast doubt on some of the previous notions concerning a latency period of several years between the exposure to a still unknown agent and the manifestation of MS. In view of atypical features in the initial phase, it would seem desirable to record cases of encephalomyelitis of undetermined origin as potential cases of MS and to register the further course for verification or exclusion.

Biological and physicochemical characterization of the major (1.40) and minor (1.45) component of infectious avian adeno-associated virus.

Two infectious components with buoyant densities of 1.40 g/cm3 and 1.45 g/cm3, designated as major (1.40) and minor (1.45) component, were detected by banding avian adeno-associated virus (AAAV) isopycnically in CsCl. In metrizamide, however, infectious AAAV banded only as a single peak at a density of 1.32 g/cm3. Biological as well as physicochemical properties of the two AAAV components recovered from CsCl density gradient were described. Concerning the minor (1.45) component, three experimental findings may suggest that the capsid structure of this AAAV population is altered in comparison with that of the major (1.40) component: (i) the sedimentation pattern characterized by an additional peak containing slower-sedimenting noninfectious material (16 S); (ii) the specific infectivity decreased by the 3.5 fold; (iii) the ready disintegration when exposed to gently denaturing conditions.

Growth of avian adeno-associated virus in chicken cells transfected with fowl adenovirus serotype 1 DNA.

Using the chloroquine-modified calcium phosphate coprecipitation technique, fowl adenovirus serotype 1 (FAV 1) DNA transfects efficiently chicken cell cultures. Infection of FAV 1 DNA transfected cells with helper dependent avian adeno-associated virus (AAAV) results in the production of AAAV progeny, being detected by an indirect immunofluorescence assay. These findings indicate that FAV 1 DNA introduced into the host cell promotes actively the growth of AAAV.

Age-associated T-lymphocyte activation through mitogens in patients with multiple sclerosis and blood donors.

In 128 patients with multiple sclerosis (MS) and 204 blood donors (control persons) the in vitro activation of 'Ficoll-purified' peripheral blood T lymphocytes was measured using the 3H-thymidine incorporation rate without (spontaneous proliferation) and with mitogen addition (concanavalin A, phytohemagglutinin). Mitogen responsiveness in control persons and MS patients decreased with age, reflecting a T-lymphocyte inherent mechanism for the diminution of responsiveness. The MS patients, ranging in age between 20 and 30 years, showed decreased mitogen responsiveness and a tendency to increased spontaneous proliferation compared to the control persons. These results could be an expression of a viral infection.

Avian adeno-associated parvovirus and Marek's disease virus: studies of viral interactions in chicken embryo fibroblasts. Brief report.

Using growth kinetics we demonstrate two effects based on interactions between the chicken herpesvirus, Marek's disease virus (MDV), and the dependovirus, avian adeno-associated virus (AAAV), in coinfected chicken embryo fibroblasts (CEF): (i) MDV provides helper activity for an efficient multiplication of AAAV; (ii) a high multiplicity of coinfecting AAAV inhibits completely the growth of MDV as well as AAAV.

Multiple sclerosis in Europe.

At a symposium held in conjunction with the 13th World Congress of Neurology, epidemiological data were presented from 23 European countries. In addition to the confirmation of the well-known north-south gradient, new details emerged on the high-prevalence areas of the British Isles and Scandinavia and on high-prevalence areas in some of the eastern and Mediterranean countries requiring more intensive exploration and confirmation. It became evident that higher prevalences existed in some places in Southern Europe previously thought to be regions of very low frequency. Limitations in the evaluation and comparison of data presented were obvious in view of differences in concepts, techniques and the intensity of surveys carried out. There was general agreement that this first collaborative attempt to map the frequency of multiple sclerosis in Europe should be followed up by standardized procedures and more cooperation in epidemiological surveys.

Herpesviruses provide helper functions for avian adeno-associated parvovirus.

The avian herpesviruses infectious laryngotracheitis virus (ILTV) and herpesvirus of turkeys (HVT), as well as the mammalian herpesvirus pseudorabies virus (PRV) were able to provide complete helper activity for the production of infectious avian adeno-associated virus (AAAV) in chicken cells. The presence of AAAV in the infected chicken cell reduced the multiplication of HVT. ILTV or PRV, however, were not affected if used as helper viruses. Infectious AAAV was determined by an indirect immunofluorescence assay and infectious herpesvirus by plaque assays.

Avian adeno-associated virus (AAAV) and fowl adenoviruses (FAV): studies of viral interactions in chicken cell cultures.

As the growth kinetics of avian adeno-associated virus (AAAV) in chicken cells demonstrate, the three serotypes of fowl adenovirus (FAV), FAV -1, -5 and -8, provide complete helper activity for the production of infectious AAAV. Under one step conditions, the growth cycle of AAAV in primary chicken kidney cell (CKC) cultures is characterised by an eclipse phase of 8 hours and an exponential increase of the virus infectivity by 4 to 5 logs until 24 hours post-adsorption (p.a.). These growth characteristics do not depend on the serotype of FAV used as helper. In chicken embryo fibroblast (CEF) cultures the eclipse phase is prolonged to 12 hours p.a. and the virus infectivity increases only by 2 logs. In addition, the low efficiency of plating of FAV -1 in this cell system does not allow one step growth curves for AAAV. In CKC and CEF cultures coinfected with FAV and AAAV the multiplication of helper FAV is reduced. The degree of growth inhibition depends on the AAV multiplicity used. Sequential infection of CKC cultures with FAV -1 and AAAV modifies the AAAV growth cycle, i.e. there is a time reduction of the eclipse phase and a decrease of the virus yield. Infectious AAAV was determined by an indirect immunofluorescence assay and infectious FAV by a plaque assay.

Comparison of the enzyme-linked immunosorbent assay (ELISA), haemagglutination inhibition test and agar gel precipitation test for detection of antibodies to avian infectious bronchitis virus.

The immune response after vaccination with infectious bronchitis virus (IBV) under field conditions was measured by the ELISA, haemagglutination-inhibition (HI) and agar-gel precipitin (AGP), tests. Vaccinations were performed in three flocks and one experimental group via the drinking water with the vaccine strains H 120 and H 52. In each flock 40 random serum samples were taken every 2 weeks and tested individually. In the experimental group blood samples were collected every week from each of the 10 chickens. The primary vaccination with H 120 resulted in a rapid increase of antibody titre as detected by ELISA followed by a slow decrease over the next few weeks. By the HI and AGP tests no antibody responses could be seen after this primary vaccination. Revaccination with the H 52 strain provoked a further increase in ELISA titres. In the experimental group, and in flock W, a similar increase occurred by the HI test and precipitating antibodies appeared. The formation of HI antibodies in flock T (nipple waterers) was somewhat retarded and precipitating antibodies were just detectable. In flock F revaccination did not result in the immediate production of HI and AGP antibodies. However, 6 weeks after revaccination a significant rise in ELISA, HI and AGP antibodies was observed, probably as the result of a field infection. It was demonstrated that, based on the higher sensitivity, the ELISA test is more suitable than HI and AGP to monitor antibody responses to vaccination against infectious bronchitis. Strain specificity in the HI test is discussed as a reason for its failure to detect antibodies after primary vaccination with the highly attenuated vaccine strain H 120.