A comparison of mutations induced by accelerated iron particles versus those induced by low earth orbit space radiation in the FEM-3 gene of Caenorhabditis elegans.

The fem-3 gene of Caenorhabditis elegans was employed to determine the mutation frequency as well as the nature of mutations induced by low earth orbit space radiation ambient to Space Shuttle flight STS-76. Recovered mutations were compared to those induced by accelerated iron ions generated by the AGS synchrotron accelerator at Brookhaven National Laboratory. For logistical reasons, dauer larvae were prepared at TCU, transported to either Kennedy Space Center or Brookhaven National Laboratory, flown in space or irradiated, returned to TCU and screened for mutants. A total of 25 fem-3 mutants were recovered after the shuttle flight and yielded a mutation frequency of 2.1x10(-5), roughly 3.3-fold higher than the spontaneous rate of 6.3x10(-6). Four of the mutations were homozygous inviable, suggesting that they were large deletions encompassing fem-3 as well as neighboring, essential genes. Southern blot analyses revealed that one of the 25 contained a polymorphism in fem-3, further evidence that space radiation can induce deletions. While no polymorphisms were detected among the iron ion-induced mutations, three of the 15 mutants were homozygous inviable, which is in keeping with previous observations that high LET iron particles generate deficiencies. These data provide evidence, albeit indirect, that an important mutagenic component of ambient space radiation is high LET charged particles such as iron ions.

Variations in disparate regions of the murine coronavirus spike protein impact the initiation of membrane fusion.

The prototype JHM strain of murine hepatitis virus (MHV) is an enveloped, RNA-containing coronavirus that has been selected in vivo for extreme neurovirulence. This virus encodes spike (S) glycoproteins that are extraordinarily effective mediators of intercellular membrane fusion, unique in their ability to initiate fusion even without prior interaction with the primary MHV receptor, a murine carcinoembryonic antigen-related cell adhesion molecule (CEACAM). In considering the possible role of this hyperactive membrane fusion activity in neurovirulence, we discovered that the growth of JHM in tissue culture selected for variants that had lost murine CEACAM-independent fusion activity. Among the collection of variants, mutations were identified in regions encoding both the receptor-binding (S1) and fusion-inducing (S2) subunits of the spike protein. Each mutation was separately introduced into cDNA encoding the prototype JHM spike, and the set of cDNAs was expressed using vaccinia virus vectors. The variant spikes were similar to that of JHM in their assembly into oligomers, their proteolysis into S1 and S2 cleavage products, their transport to cell surfaces, and their affinity for a soluble form of murine CEACAM. However, these tissue culture-adapted spikes were significantly stabilized as S1-S2 heteromers, and their entirely CEACAM-dependent fusion activity was delayed or reduced relative to prototype JHM spikes. The mutations that we have identified therefore point to regions of the S protein that specifically regulate the membrane fusion reaction. We suggest that cultured cells, unlike certain in vivo environments, select for S proteins with delayed, CEACAM-dependent fusion activities that may increase the likelihood of virus internalization prior to the irreversible uncoating process.

[Psoriasis and bullous dermatoses]. / Psoriasis und bullöse Dermatosen.

In the last five years we observed in Berlin seven cases of psoriasis vulgaris combined with bullous eruptions of the pemphigoid type. Exogenious factors provoking the bullous eruptions were sun exposure, photochemotherapy and treatment with dithranol. These factors did not cause contact allergy of type IV, but pemphigoid eruption which could be characterised by immunfluorescence. This, was accompanied in two cases with high numbers of eosinophils in tissue and blood. The results show similarities with the findings of Person and Rogers who have shown the manifestation of otherwise subclinical pemphigoid in patients being treated for psoriasis.

[Determination of immunoglobulins in acute and chronic coronary disease]. / Immunoglobulinbestimmungen bei akuten und chronischen Koronargefässerkrankungen

51 patients with chronic ischaemic heart disease showed on the average increases of IgA and IgG, but a significance concerning a control group could not be calculated. Compared with the normal group 41 patients with acute myocardial infarction did not reveal a significant increase of all three immunoglobulins. The observations of the course after myocardial infarction had the following result: During the first five days IgG in the majority decreased to 90% of the initial value and in the second to third week it increased to a maximum of on the average 150% of the initial value. 8 patients did not show a change of the IgG-level after infarction, in 4 patients the IgG-level still continuously decreased also in the second week. In 23 patients IgA increased to the double in the second and third week, in 18 patients it remained uninfluenced. The increase of IgM was to be established in 15 patients in whom at the same time in increase of IgA appeared. A relation between the values of IgG and the clinical parameters of the myocardial infarction could not be proved.