Stimulatory and suppressive effects of infection of dendritic cells with HIV-1.

Two effects of HIV infection on human dendritic cells (DC) in vitro have been examined. The first was the stimulation of primary responses to HIV antigens in autologous lymphocytes from normal donors. When DC were exposed to HIV (10(4) TCID/10(5) cells) for up to 24 h before addition to autologous lymphocytes, a marked primary proliferative response to the virus was observed. No proliferative response was seen when the period of pre-exposure of DC to virus was extended. Cytotoxic T cells specific for HIV-infected target cells developed in stimulated cultures. The second effect of HIV infection of DC was to block responses to other antigens, such as alloantigens and the recall antigens tetanus toxoid and influenza virus. This inhibitory effect was only evident when the DC were exposed to HIV for longer than 24 h before being added to cultures. These in vitro studies suggest that infection of DC can produce both stimulatory and inhibitory responses in lymphocytes. Such effects operating through DC might underlie in vivo activity of HIV both in stimulating the proliferation of lymphocytes (e.g., in persistent generalised lymphadenopathy) and in the development of immunosuppression.     

Parasite-susceptibility phenotypes of F1 Biomphalaria glabrataprogeny derived from interbreeding Schistosoma mansoni-resistant and -susceptible snails

In an effort to investigate the 'flow' of parasite-resistance genes through laboratory snail populations, we determined the susceptibility of progeny snails from freely interbreeding parasite-susceptible and parasite-resistant parents. Five parental populations of Biomphalaria glabrata were used to generate the progeny snails. Three of them contained different proportions of Schistosoma mansoni-susceptible albino snails (NMRI stock) and S. mansoni-resistant pigmented snails (BS-90), while single stock controls comprised the other two parental populations. F(1) snails from each parental population were exposed to S. mansoni miracidia. Some of the progeny snails were exposed as juveniles, others as adults. According to Hardy-Weinberg principle predictions, the F(1) generation from the three pigmented/albino parental populations displayed higher than expected numbers of pigmented (resistant) snails and lower than expected numbers of albino (susceptible) snails. Among the assumptions of the Hardy-Weinberg principle that were not met within these populations could include non-random mating, unequal fecundity, different hatching and survival rates of different genotypes, or other life-history differences between snail stocks. It is clear, though, that for these two laboratory snail stocks there is no fitness cost attached to genetic resistance to the parasite.     

Familial Similarities of Changes in Cognitive, Behavioral, and Physiological Variables in a Cardiovascular Health Promotion Program

A number of studies have demonstrated that physiological andbehavioral cardiovascular disease (CVD) risk factors aggregatewithin families. This fact, and the potential mediating rolethat the family plays in behavior change, have led to the developmentof family-based CVD risk reduction programs, including the SanDiego Family Health Project. The aggregation of behavioral,physiological, and cognitive changes within families was assessedduring a 1-year intervention. We found evidence of modest butsignificant aggregation of change. There was more aggregationof change in behavioral variables than in physiological or cognitivevariables. More significant correlations were found among 3-dayfood record measures than among 24-hour recall dietary measures,suggesting an influence of assessment method. Aggregation ofchange within families was stronger within generations thanacross generations. These data point to the importance of involvingall age groups in health promotion programs.     

Clinical and pathological characterization of an osteoma in a barred owl

Osteomas are rare in birds. An osteoma of the left proximal radius was diagnosed in an adult barred owl based on gross, radiographic, and pathologic findings.     

Regional mapping of the gene encoding dihydroorotate dehydrogenase,an enzyme involved in UMP synthesis,electron transport,and superoxide generation,to human chromosome region 16q22

De novo UMP synthesis is a critical metabolic pathway for nucleic acid synthesis and for a variety of metabolic pathways. The pathway is a target for many widely used cancer chemotherapy agents, several of which are pyrimidine analogs. Humans and cattle have been described with mutations in UMP synthesis that lead to serious inborn errors of metabolism. Dihydroorotate dehydrogenase (EC 1.3.3.1) (DHODH) carries out the fourth committed step in the pathway and may also be important for mitochondrial electron transport and oxygen radical metabolism. We report here that the gene encoding this enzyme in humans is located in the chromosomal region 16q22. With the mapping of DHODH, the mapping of all the steps of UMP synthesis is complete. All three genes involved map to different human chromosomes. This information is important in consideration of regulation of UMP synthesis in mammals, including humans.     

Neisseria meningitidis bacteremia in association with deficiency of the sixth component of complement.

The serum of a 26-year-old black man with a recent episode of meningococcemia complicated by meningitis and arthritis was found to lack hemolytic complement activity. The sixth component of complement was not detected by functional or immunochemical assays whereas other components were normal by hemolytic assay. His fresh acute-phase serum lacked complement-mediated bactericidal activity against the homologous strain of Neisseria meningitidis, but the addition of fresh normal serum or purified C6 restored bactericidal activity as well as hemolytic activity. The absence of C6 activity could not be accounted for on the basis of an inhibitor. Opsonization and chemotaxis functioned normally. Histocompatibility typing of family members did not demonstrate evidence for genetic linkage of C6 deficiency with the major histocompatibility loci. This report represents the first published case of C6 deficiency associated with bacteremic Neisseria infections in which antimeningococcal bactericidal antibodies have been definitively demonstrated against the homologous strain in the acute phase of the illness.     

External fixation of unstable pelvic ring fractures: comparative rigidity of some current frame configurations

The effectiveness of external fixation in the stabilisation of pelvic ring fractures was studied in a laboratory cadaveric series. Shearing displacements occurring at sacroiliac joint and symphysis pubis dislocation sites, due to simplified longitudinal loading of the sacrum in an Instron unit, were monitored using variable-impedence transducers. The rigidity of fixation was compared for the Slätis and the Bonnel single anterior frames, for coupled and uncoupled double anterior frames, and for combined anterior-plus-posterior fixation achieved with separate transfixation pin clusters, with through-and-through pin clusters, or with a posterior screw plate. The data showed that the use of posterior fixation provided greatly enhanced stabilisation compared to that achieved with anterior fixation alone. The complex double anterior frames performed only slightly better than did the simpler single anterior frames. In no case, however, was it possible to recover rigidity levels approaching those of the intact pelvis. The results suggest that the transfixation pin arrangement is the most important determinant of pelvic fixation stability, and that further investigation of posterior screw-plate fixation is warranted.     

Atlas of Hox gene expression in the developing kidney.

Hox genes often play important roles in segment identity determination and organogenesis. To better understand the roles of Hox genes during kidney development, we performed an extensive analysis of their expression patterns. Section in situ hybridizations were used to define the expression of 37 Hox genes at embryonic day (E) 12.5, E13.5, E15.5, and E17.5 of kidney development. Several interesting principles emerged. First, the concept of colinearity was preserved. Hox genes from the more 3' positions in clusters were more often expressed in the ureteric bud, which is derived from the anterior of the intermediate mesoderm. Second, Hox genes were expressed throughout the ureteric bud without any segment specificity. Third, in the different segments of the forming nephron we did observe overlapping domains of Hox gene expression, which initiated distally at the junction between the nephron and ureteric bud, and extended proximally variable distances. Finally, we observed that paralogous Hox genes often showed surprisingly diverse expression patterns. Indeed, contiguous genes on a single cluster more often showed similar expression patterns than paralogs. In summary, the resulting atlas of Hox gene expression provides a foundation for further study of the overlapping functions Hox genes in the developing kidney.