Generalized AA-amyloidosis in a 58-year-old Caucasian woman with an 18-month history of gastrointestinal tuberculosis

 We report on a 58-year-old Caucasian woman who went to a general practitioner about recurrent abdominal pain, night sweats and weight loss of a few weeks’ duration. Once gynaecological disease had been ruled out, the patient was admitted to hospital with severe abdominal pain and intestinal obstruction and a right-sided hemicolectomy was performed. Following the investigation of osteolytic lumbar vertebrae, 18 months after visiting the general practitioner the patient was finally found to be suffering from generalized AA-amyloidosis secondary to gastrointestinal tuberculosis. This had been misinterpreted as Crohn’s disease. Re-examination of the specimens from the right-sided hemicolectomy demonstrated that scanty deposits of AA-amyloid were present 9 months after the first presentation. AA-amyloid can thus be present in serious inflammatory disease even during the first 9 months after the initial clinical presentation. Received: 23 June 1998 / Accepted: 19 August 1998     

Viral hepatitis in Germany: poor vaccination coverage and little knowledge about transmission in target groups

Background  

In Germany, vaccination against hepatitis B is recommended for infants, children and adolescents since 1995 and for specific target groups since 1982. Little is known about knowledge about viral hepatitis and attitudes toward hepatitis B vaccination-factors likely to influence vaccine uptake.     

Females do not have more injury road accidents on Friday the 13th

Background

This study reinvestigated the recent finding that females – but not males – die in traffic accidents on Friday the 13th more often than on other Fridays (Näyhä S: Traffic deaths and superstition on Friday the 13th. Am J Psychiatry 2002, 159: 2110–2111). The current study used matched setting and injury accident data base that is more numerous than fatality data. If such an effect would be caused by impaired psychic and psychomotor functioning due to more frequent anxiety among women, it should also appear in injury crashes.

Methods

We used the national Finnish road accident database for 1989–2002. To control seasonal variation, 21 Fridays the 13th were compared in a matched design to previous and following Fridays, excluding all holidays, on number of accidents, male/female responsibility for accidents, and the number of dead, injured and overall number of active participants (drivers, pedestrians and bicyclists) as a consequence of the accident.

Results

There were no significant differences in any examined aspect of road injury accidents among the three Fridays, either in females or males. Women were not overrepresented in crashes that occurred on Fridays 13th.

Conclusion

There is no consistent evidence for females having more road traffic crashes on Fridays the 13th, based on deaths or road accident statistics. However, this does not imply a non-existent effect of superstition related anxiety on accident risk as no exposure-to-risk data are available. People who are anxious of "Black Friday" may stay home, or at least avoid driving a car.

     

SARS: retrospective cohort study among German guests of the Hotel 'M', Hong Kong

Hong Kong played a pivotal role in the international spread of the Severe Acute Respiratory Syndrome (SARS): a doctor who spent the night of 21-22 February 2003 at Hotel 'M' was identified as the index case for four national and international clusters of SARS. In parallel to the international collaborative study led by WHO and United States, a retrospective study on the cohort of German persons staying at Hotel 'M' was conducted. The inclusion criteria covered a period from 21 February to 3 March 2003 to allow the detection of cases possibly due to environmental contamination. In the twenty-one German guests traced as having stayed at Hotel "M" during this period, one case of laboratory confirmed SARS was found. The case history suggests that close vicinity to the index patient may have played a role in transmission. In line with findings of environmental investigations in the hotel, environmental contamination should be considered as a possible source of infection.     

Ocular vestibular-evoked myogenic potential (oVEMP) to test utricular function: neural and oculomotor evidence

A new test for utricular function has recently been introduced and validated, namely the ocular vestibular-evoked myogenic potential (oVEMP), which refers to the myogenic potentials recorded by surface EMG electrodes beneath both eyes in response to bone conducted vibration (BCV) of the head or air conducted sound (ACS). The oVEMP test differs from another vestibular-evoked myogenic potential recorded by surface EMG electrodes over the sternocleidomastoid muscles in that the cervical vestibular-evoked myogenic potential (cVEMP) due to saccular activation is measured. oVEMP is a reliable clinical test that relies on extensive physiological evidence from studies on guinea pigs, and in particular on recording the vestibular primary afferent responses to BCV, demonstrating that the same BCV causes similar eye movements in both guinea pigs and humans. This review briefly integrates the most recent physiological and behavioural evidence that substantiates the clinical use of oVEMP.     

Generation of ordered protein assemblies using rigid three-body fusion

Protein nanomaterial design is an emerging discipline with applications in medicine and beyond. A long-standing design approach uses genetic fusion to join protein homo-oligomer subunits via α-helical linkers to form more complex symmetric assemblies, but this method is hampered by linker flexibility and a dearth of geometric solutions. Here, we describe a general computational method for rigidly fusing homo-oligomer and spacer building blocks to generate user-defined architectures that generates far more geometric solutions than previous approaches. The fusion junctions are then optimized using Rosetta to minimize flexibility. We apply this method to design and test 92 dihedral symmetric protein assemblies using a set of designed homodimers and repeat protein building blocks. Experimental validation by native mass spectrometry, small-angle X-ray scattering, and negative-stain single-particle electron microscopy confirms the assembly states for 11 designs. Most of these assemblies are constructed from designed ankyrin repeat proteins (DARPins), held in place on one end by α-helical fusion and on the other by a designed homodimer interface, and we explored their use for cryogenic electron microscopy (cryo-EM) structure determination by incorporating DARPin variants selected to bind targets of interest. Although the target resolution was limited by preferred orientation effects and small scaffold size, we found that the dual anchoring strategy reduced the flexibility of the target-DARPIN complex with respect to the overall assembly, suggesting that multipoint anchoring of binding domains could contribute to cryo-EM structure determination of small proteins.

There is considerable interest in the design of novel protein assemblies, for example, to develop cryogenic electron microscopy (cryo-EM) scaffolds to aid in structure determination (1, 2) and protein nanoparticle vaccines (3, 4). Many studies have utilized 1) genetic fusion of α-helices at N and C termini or 2) protein interface design to drive assembly of symmetric protein homo-oligomers into a larger symmetric nanoparticle or lattice. The genetic fusion route was originally demonstrated with the creation of a tetrahedral protein nanocage and fiber (5) and has since been used to generate two-dimensional (2D) layers (6), a porous cube (7), additional tetrahedra (8, 9), octahedra (10), and icosahedra (11, 12). Strengths of the fusion approach are that it is relatively straightforward, not inherently destabilizing, and guarantees the intended stoichiometry and specificity between fusion partners. Despite its simplicity and success, several aspects of genetic fusion complicate its use. Genetic fusion is best applied with α-helical termini, as this imparts some rigidity between the fused domains, but termini are not always α-helical or physically accessible. Furthermore, the number of possible sequence alignments between any given pair of building blocks is finite and this, in turn, limits the number of geometric solutions for a desired symmetric architecture. This can complicate or preclude the use of fusion methods in assembly design, especially when a particular protein building block is required for a downstream application. Finally, flexibility is often introduced at the point of fusion, even with α-helical linkers and certainly with disordered linkers. In the best cases, model deviations are subtle (8, 13); however, varying levels of unintended assembly products are also commonly observed. In contrast, the noncovalent protein interface design approach bypasses considerations of termini and their alignment. Interface design is compatible with the free rotation and translation of building blocks along their axes (14), so the set of valid geometric solutions is technically unlimited. The drawback to interface design is that it requires the creation of a new soluble and specific interface without destabilizing either protein. Like fusion, the interface design route to the protein nanomaterial production has achieved considerable success (4, 15–20).Among applications for genetic fusion is the creation of cryo-EM scaffolds (1, 2, 21–23): If a small target protein can be immobilized and rigidly bound onto a larger symmetric assembly, EM particle images can be more readily aligned and classified, and structures too small to analyze alone could then become amenable to structure determination. Yeates et al. demonstrated the potential of this approach by fusing a designed ankyrin repeat protein (DARPin) (24, 25) to the outside of a previously designed protein nanocage (1); the bound green fluorescent protein (GFP) target was resolved at 3.8 Å resolution with only a single α-helical fusion anchoring the DARPin.     

Glucocorticoid receptors in lymphocytes and stability of kidney graft function

The glucocorticoid receptors in lymphocytes of patients treated with glucocorticoids aftert kidney transplantation have been studied in order to determine whether abnormalities in corticosteroid binding and trans-activation of steroid-receptor complexes, i. e., their translocation into nuclei, may contribute to the resistance of patients to glucocorticoid therapy. The patients were divided into two groups, according to graft stability: patients with stable graft function and those with chronic allograft rejection. The study revealed changes in both level and binding affinity of glucocorticoid receptors in peripheral blood lymphocytes from patients with chronic graft rejection, compared with control level, as well as with values of patients with stable graft function. These data indicate that sensitivity to glucocorticoids depends, at least in part, on the alterations of glucocorticoid receptors. The receptor translocation into nuclei indicates that unknown post-receptor events might also be involved in glucocorticoid resistance that seriously impair successive glucocorticoid therapy after organ transplantation. Further examination of glucocorticoid receptors in cases of organ transplantation seems warranted. Received: 21 March 2001 / Accepted: 14 December 2001     

Hepatitis B and C risk factors in Germany--results of the national surveillance

Collection of risk factor data is part of the national surveillance of hepatitis B and C in Germany. After modifications of risk factor surveillance had been implemented in September 2003, the response rate for data on risk factors increased markedly. For the period between September 2003 and August 2004, information on risk factors (at least one "yes" or "no" answer) was available for 66% (1853) of all notified hepatitis B cases and for 67% (5813) of all notified hepatitis C cases. More than 30% of those hepatitis B cases occurred among risk groups for whom hepatitis B immunisation is recommended by the German Advisory Committee on Immunisation (STIKO). Of the hepatitis C cases with risk factor data, 40% reported previous or continuing injecting drug use (IDU). IDU was predominant among young men (78% among men, aged 15 to 29 years) and can explain the comparatively high incidence observed in young adults, especially among men. The impact of other risk factors (e. g. medical interventions) cannot be quantified without a proper control group. The results of this study demonstrate that--in addition to the hepatitis B immunisation of children and adolescents--vaccination coverage of specific risk groups, as defined by the STIKO, should be increased. Measures to prevent hepatitis C have to focus on intravenous drug users and clearly have to be intensified.