[Wound botulism in heroin addicts in Germany]. / Wundbotulismus bei Heroinabhängigen in Deutschland.

HISTORY AND ADMISSION FINDINGS: 5 heroin addicts (aged 31-44 years; 1 female, 4 men) presented with a history of blurred vision and diplopia followed by dysarthria. 3 of the patients also developed respiratory failure requiring long-term ventilatory support. Physical examination revealed cranial nerve deficits and abscesses at injection sites in 3 of them. DIAGNOSIS: In 4 patients wound botulism was diagnosed on the basis of symptoms, course of the illness and response to specific treatment. Clostridium botulinum was grown from wound swab in one patient. TREATMENT AND COURSE: Two of the patients, having been injected with antitoxin immediately after admission, were discharged almost symptom-free after only a few days. Adjuvant antibiotics and, in 3 patients, surgical débridement of the abscesses were needed. CONCLUSIONS: Progressive cranial nerve pareses in addicts who inject drugs intravenously or intramuscularly should raise the suspicion of wound botulism and require hospitalization. While indirect demonstration of toxin supports the diagnosis, false-negative results are common.

Sinusoidal forearm tracking with delayed visual feedback. I. Dependence of the tracking error on the relative delay.

During forearm tracking of a sinusoidally moving target matching of proprioceptive and visual feedback was altered by introducing different visual delays. In five normal subjects seven target frequencies were tested ranging from 0.3 to 1.5 Hz. For each target frequency nine different delays were used ranging from 0 to 120% of the cycle duration with target frequency and delay being varied randomly. Tracking error revealed a cyclic behaviour with an increase up to delays of about 50% of the target cycle duration and an improvement for delays larger than 50%. Modulation of response frequency was less pronounced compared with tracking error variation but also was dependent on relative phase. The response frequency matched the target frequency at delays of 0 and 100% of cycle duration and was slightly lower than the target frequency with relative delays of about 50%. The introduction of a visual delay during sinusoidal forearm tracking leads to a spatial in addition to the temporal mismatch between proprioception and vision. The temporal and the spatial incompatibility influence the tracking performance differentially.

Sinusoidal forearm tracking with delayed visual feedback. II. Dependence of the relative phase on the relative delay.

The influence of delayed visual feedback on the phase relationships between target and response signal during a sinusoidal tracking task was analysed in five normal subjects. Target frequency was varied systematically between 0.3 and 1.5 Hz, and the delay between 0 and 120% of the target cycle duration. For each subject, 63 trials were recorded. Phase parameters (relative phase, absolute relative phase and percentage of positive relative phases) revealed a clear dependence on relative delay but not on target frequency. With relative delays close to 0 and 100% of the target cycle duration, subjects successfully tracked the target signal with a small phase lag. With delays in the 30-90% range, larger phase differences were observed. Furthermore, the (delayed) response signal usually preceded the target signal in this delay range. These findings provide further evidence for a dependence of tracking error on external delays in the visual feedback loop, and indicate that delays of about 50% of the movement cycle are more difficult to handle than are smaller or larger delays. The results are discussed with regard to the influence of different control strategies (feedback, feedforward) and different types of feedback (such as vision and proprioception) on motor control.

Uptake and nuclear transport of Neisseria IgA1 protease-associated alpha-proteins in human cells.

Pathogenic Neisseria species, the causative agents of gonorrhoea and bacterial meningitis, encode a family of polymorphic exo-proteins which are autoproteolytically processed into several distinct extracellular components, including an IgA1 protease and an alpha-protein. IgA1 protease, a putative virulence determinant, is a sequence-specific endopeptidase known to cleave human IgA1, but additional target proteins have been postulated. The physical linkage of IgA1 protease and alpha-protein suggests a functional relationship of both precursor components. Previous work has shown that alpha-protein is essential neither for extracellular transport nor for the proteolytic activity of IgA1 protease. Intriguingly, alpha-proteins carry amino acid sequences reminiscent of nuclear location signals of viral and eukaryotic proteins. Here we demonstrate the functionality of these nuclear location signal sequences in transfected eukaryotic cells. Chimeric alpha-proteins show nuclear transport and selectively associate with nucleolar structures. More importantly, native purified alpha-proteins are capable of entering certain human primary cells from the exterior via an endocytotic route and accumulate in the nuclei. The neisserial alpha-proteins share several features with eukaryotic transcription factors, such as the formation of dimers via a heptad repeat sequence. We propose a role for alpha-proteins in the regulation of host-cell functions. As the alpha-proteins are covalently connected with IgA1 protease they may also serve as carries for the IgA1 protease into human cells where additional proteolytic targets may exist. Neisseria meningitidis, which locally colonizes the nasopharyngeal mucosa of many human individuals without apparently causing symptoms, secretes this nucleus-targeted factor in large quantities.

Mycoplasma contamination in human tumor cell lines: effect on interferon induction and susceptibility to natural killing.

Cleaning of human tumor cell lines from arginine-dependent nonfermentative Mycoplasma orale 1 (MO1) by a recently developed technique profoundly altered several in vitro properties of the cell lines. Four melanoma lines (Mel I, Mel St, Mel K, IGR3) and 1 ovarian carcinoma line (Ro) induced human leukocyte interferon (IFN-alpha) only in the mycoplasma-infected state and not in the mycoplasma-free state. MO1-infected tumor lines were generally more susceptible to natural killer (NK) cell-mediated lysis than their mycoplasma-free counterparts. Reinfection of cleaned tumor lines with MO1 restored their interferonogenicity and the increased susceptibility to NK lysis. Thus, the amplifying role of MO1 infection on NK target lysis occurred in connection with an increased production IFN-alpha during the assay period. The human erythroleukemia cell line K562 was exceptional in that it also induced high levels of IFN in an apparently mycoplasma-free state and was unaffected in its susceptibility ot NK lysis by infection with MO1. Possible implications of these findings for the biologic significance of the NK reaction are discussed.

Macrophages overcome mycoplasma infections of cells in vitro.

Mycoplasmal infections still cause severe problems in cell cultures, particularly permanent lines, and although rapid detection is possible the only methods proposed for the elimination of the mycoplasma are either laborious or unsatisfactory. Treatment with antibiotics often leads to the development of resistance and we have found it more successful to passage contaminated cells in nude (thymusless) mice although the cells cannot always be recovered. But when the resulting subcutanous tumours can be collected, the cells are both free of mycoplasma and accompanied by a large number of macrophages. Because nude mice have no T cell-dependent immune response, it seemed possible that the macrophages could be responsible for the elimination of the mycoplasma. The experiments reported here support this hypothesis, and have led to a rapid and reproducible technique for eliminating mycoplasma in vitro by a brief co-cultivation of contaminated cells with mouse macrophages, in the presence of antibiotics.