Amyloid: morphology and toxicity.

We have expressed transthyretin (TTR) mutants which have significantly destabilised tetramers that aggregate into amyloid fibrils via a series of intermediates. We used atomic force microscopy to follow the morphology of aggregates during fibril formation. Initially, amorphous aggregates are formed that subsequently mature into fibrillar structures. This observation is interpreted as an optimisation of beta-strand registers. The rate of aggregation and maturation is highly temperature-dependent suggesting that entropic forces significantly contribute to stability. In addition, we identified a correlation between the presence of early formed aggregates of TTR and cytotoxicity. The toxic response was mediated via an apoptotic mechanism. The fact that early formed amorphous aggregates, but not more mature fibrils, exert a toxic response suggests that the rate of fibril formation may be a critical parameter. We propose that a slow rate of aggregation facilitates an increased concentration of a toxic intermediate.     

Aqueous humor polyamines and alkaline phosphatase activity in endotoxin-induced uveitis: correlations to diverse leukocyte subsets.

The polyamines putrescine, spermidine and spermine have been proposed to be a part of the acute phase inflammatory response. They have been shown to be useful markers for cellular kinetics and change with various pathological conditions. The hypothesis that aqueous humor polyamines could be used to follow the time course of an endotoxin-induced inflammation in the eye was investigated. Additional parameters studied were the amount of aqueous leukocytes, alkaline phosphatase activity, distribution of leukocyte subsets and breakdown of the blood-aqueous barrier. Aqueous leukocytes, protein, alkaline phosphatase activity, putrescine and acetylated spermidine increased significantly as a response to inflammation during the first days after uveitis induction. Spermidine decreased 24 h after injection and seemed to rise thereafter. The different polyamines, except spermidine, correlated to the diverse infiltrating leukocyte subsets. These observations indicate that aqueous polyamines may be applied as valid markers for inflammation in the eye.     

Bronchoscopy of symptom free patients infected with human immunodeficiency virus for detection of pneumocystosis.

No evidence of Pneumocystis carinii infection was found in eight symptom free patients who were positive for the human immunodeficiency virus and who underwent bronchoscopy, bronchoalveolar lavage, and brush biopsy. This suggests that the presence of Pneumocystis carinii in bronchoscopy material is likely to indicate pneumocystis infection.     

Strong natural selection causes microscale allozyme variation in a marine snail.

Natural selection is one of the most fundamental processes in biology. However, there is still a controversy over the importance of selection in microevolution of molecular traits. Despite the general lack of data most authors hold the view that selection on molecular characters may be important, but at lower rates than selection on most phenotypic traits. Here we present evidence that natural selection may contribute substantially to molecular variation on a scale of meters only. In populations of the marine snail Littorina saxatilis living on exposed rocky shores, steep microclines in allele frequencies between splash and surf zone groups are present in the enzyme aspartate aminotransferase (allozyme locus Aat; EC. 2.6.1.1). We followed one population over 7 years, including a period of strong natural perturbation. The surf zone part of the population dominated by the allele Aat100 was suddenly eliminated by a bloom of a toxin-producing microflagellate. Downshore migration of splash zone snails with predominantly Aat120 alleles resulted in a drastic increase in surf zone frequency of Aat120, from 0.4 to 0.8 over 2 years. Over the next four to six generations, however, the frequency of Aat120 returned to the original value. We estimated the coefficient of selection of Aat120 in the surf zone to be about 0.4. Earlier studies show similar or even sharper Aat clines in other countries. Thus, we conclude that microclinal selection is an important evolutionary force in this system.     

Cell lines with spontaneous secretion of pregnancy-associated alpha 2-globulin.

Pregnancy-associated alpha 2-globulin (PA alpha 2G) was quantitated by radioimmunoassay in culture media from 34 exponentially growing human cell lines. Only 8/34 cell lines produced PA alpha 2G. The highest secretion was found in cell lines of histiocytic lymphoma origin while it was low in some carcinoma-derived lines. The results may support an assumption that PA alpha 2G is a normal cell product of B-lymphoid, monocytic and epithelial cells but may also simply indicate that ectopic PA alpha 2G production is especially common in tumors derived from such cells. The availability of PA alpha 2G-producing cell lines should facilitate studies of the immunoregulatory role of this protein.     

Das Bewegungszentrum in der Lendenwirbels?ule bei Flexion und Extension

Zusammenfassung In zwei lumbalen Segmenten hat man mit der Tomographie die Lage der Bewegungsachse bei Flexion und Extension bestimmt. Es wurde gefunden, daß die Achse im Anschluß an die Bandscheibe liegen kann, aber in der Mehrzahl der Fälle lag die Achse auf bedeutendem Abstand von ihr und immer unterhalb dieser Bandscheibe. In extremen Fällen sah man, daß die Bewegungsachse durch die nächst unterhalb liegende Bandscheibe ging.

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Motion centre in flexion and extension of the lumbar spine

Summary The location of the axis of movement between the vertebrae in two lumbar segments was determined by means of tomography in flexion and extension. It was found that the axis may be situated in the disc or in its immediate vicinity but in the majority of cases it lay outside the disc at considerable distances from it. Then it was always below the disc. In extreme cases the axis was seen to pass through the intervertebral disc of the segment below.