Molecular typing shows a high level of HLA class I incompatibility in serologically well matched donor/patient pairs: implications for unrelated bone marrow donor selection

In comparison with HLA-matched sibling bone marrow transplants, unrelated donor transplants are associated with increased graft-versus-host disease and graft failure. This is likely in part due to HLA incompatibilities not identified by current matching strategies. High resolution DNA-based typing methods for HLA class II loci have improved donor selection and treatment outcome in unrelated donor bone marrow transplantation. By using DNA-based typing methods for HLA-A and -B on a cohort of 100 potential bone marrow donor/patient pairs, we find that serological typing for HLA class I is limited in its ability to identify incompatibilities in unrelated pairs. Furthermore, the incompatibilities identified are associated with the presence at high frequency of alloreactive cytotoxic T-lymphocyte precursors. DNA typing also indicates that HLA-C mismatches are common in HLA-A and -B serologically matched pairs. Such mismatches appear to be significantly less immunogenic with respect to cytotoxic T-lymphocyte recognition, but are expected to influence natural killer cell activity. Thus, improved resolution of HLA class I shows many previously undisclosed mismatches that appear to be immunologically functional. Use of high resolution typing methods in routine matching is expected to improve unrelated donor selection and transplant outcome.     

Cloning of aas, a gene encoding a Staphylococcus saprophyticus surface protein with adhesive and autolytic properties

A gene encoding a novel cell wall-associated protein of Staphylococcus saprophyticus that binds fibronectin and to sheep erythrocytes has been cloned and sequenced. The 4392 bp open reading frame codes for an amino acid sequence that is quite similar to the Atl, an autolysin, of Staphylococcus aureus and to the AtlE of S. epidermidis. The two regions of most pronounced homology code for an N-acetyl-muramyl-L-alanine amidase and for an endo-beta-N-acetyl-D-glucosaminidase. The cloned protein lysed cells of S. saprophyticus and Micrococcus luteus exogenously. Subcloning localized the enzymatic activities to the regions of high homology and demonstrated that the interposed sequence is responsible for the adhesive activities. Two allelic replacement mutants were constructed that lacked autolytic activity and adhesive properties. The N-terminal portion of the protein contains seven highly conserved, contiguous repeats with no similarity to published sequences. It lacks the motifs typical of Gram-positive surface proteins and shows a different overall organization. This autolysin/adhesin of S. saprophyticus (Aas) appears to represent a new class of staphylococcal adhesins.     

Synaptic vesicles have two distinct recycling pathways

In this paper, evidence is presented that two distinct synaptic vesicle recycling pathways exist within a single terminal. One pathway emanates from the active zone, has a fast time course, involves no intermediate structures, and is blocked by exposure to high Mg2+/low Ca2+ saline, while the second pathway emanates at sites away from the active zone, has a slower time course, involves an endosomal intermediate, and is not sensitive to high Mg2+/low Ca2+. To visualize these two recycling pathways, the temperature-sensitive Drosophila mutant, shibire, in which vesicle recycling is normal at 19 degrees C but is blocked at 29 degrees C, was used. With exposure to 29 degrees C, complete vesicle depletion occurs as exocytosis proceeds while endocytosis is blocked. When the temperature is lowered to 26 degrees C, vesicle recycling membrane begins to accumulate as invaginations of the plasmalemma, but pinch-off is blocked. Under these experimental conditions, it was possible to distinguish the two separate pathways by electron microscopic analysis. These two pathways were further characterized by observing the normal recycling process at the permissive temperature, 19 degrees C. It is suggested that the function of these two recycling pathways might be to produce two distinct vesicle populations: the active zone and nonactive zone populations. The possibility that these two populations have different release characteristics and functions is discussed.     

Features that distinguish the smooth-pursuit eye-tracking performance of schizophrenic, affective-disorder, and normal individuals.

Examined the eye-tracking records of 25 schizophrenic (mean age 37.6 yrs), 25 unipolar (mean age 37.9 yrs), 24 bipolar (mean age 36 yrs), and 46 medical control (mean age 35 yrs) patients. All the psychiatric patients were in symptom remission. All three psychiatric groups produced more oscillations than controls, and spiky tracking was correlated with poor performance as indexed by the production of large saccades. Schizophrenics did, however, produce smaller saccades and tracked with more phase lag than did each of the other groups. Results suggest that the smooth-pursuit system of schizophrenics is functionally different from that of normal people. Use of the phase lag as a potential marker of schizophrenia is discussed. (33 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Social and developmental experience and interspecific aggression in rats.

Measured the aggressive behavior of a total of 176 male Long-Evans rats in 3 experiments. Ss raised in social isolation from weaning showed significantly more interspecific aggressive behavior than littermates raised with peers, as measured by the proportion initiating a killing attack against frogs in a 20-min arena test. Ss in 6 cross-species rearing conditions with frogs and cockroaches failed to form social attachments. When tested individually, these Ss killed the alien species as often as or more often than did controls. A significant number of adult Ss selected for nonagressive responses became killers after witnessing aggression in other Ss. (33 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)