Immunity after treatment of human schistosomiasis: association between cellular responses and resistance to reinfection.

Previous studies have demonstrated the development of an age-dependent resistance to reinfection after chemotherapeutic cure of the helminthic parasite Schistosoma mansoni. Here we report on a longitudinal investigation of cell-mediated responses in infected individuals before and after treatment which was designed to outline those parameters important in mediating a protective response. A well-defined study group of 89 individuals with an age range of 9 to 35 years was selected from an area of high S. mansoni transmission in the Machakos district of Kenya. Peripheral blood mononuclear cell proliferation and cytokine production (interleukin-2 [IL-2], gamma interferon IL-5, IL-4, and tumor necrosis factor) in response to different crude life cycle-stage antigens of S. mansoni were assessed longitudinally in vitro before, 3 months after, and 1 year after treatment. Detailed statistical analyses of the results from this study have indicated a clear negative association between the proliferative responses to adult- and schistosomulum-stage antigens and subsequent reinfection intensity in older individuals (14 to 35 years) which was not present in the younger individuals (9 to 13 years). This association was significant even after the effects of age, sex, and exposure had been accounted for in multiple regression analyses. Cytokines were detected predominantly in response to adult worm and egg antigen extracts. An inverse association between the two cytokines gamma interferon and IL-5 was detected in response to all antigens at the three time points investigated, indicating cross-regulation in the production of these two mediators. Differences in antigen-specific cytokine levels between the two age groups were detected, with significantly higher IL-5 levels detected in the older (more resistant) age group. An inverse correlation between this cytokine and reinfection was detected but could not be dissociated from the effects of age and exposure in multiple regression analysis.     

Recruiting and retaining GPs and patients in intervention studies: the DEPS-GP project as a case study

Background  

Recruiting and retaining GPs for research can prove difficult, and may result in sub-optimal patient participation where GPs are required to recruit patients. Low participation rates may affect the validity of research.     

Effect of a new synthetic serum replacement on insulin and somatostatin secretion from isolated rat pancreatic islets in long-term culture

Summary Serum contains insulin degrading components. We have evaluated the insulin and somatostatin secretion from isolated rat pancreatic islets during a 2-wk culture period using three different serum-containing media, and one serum-free medium with a synthetic serum replacement. Islets incubated in serum-free medium elicited significantly higher daily insulin and somatostatin secretions than islets incubated in the serum-containing media. After a 2-wk culture period, islets from the serum-free medium secreted significantly more insulin and somatostatin than islets cultured in other media when stimulated with 25 mmol/liter glucose together with 15 mmol/liter theophylline. We conclude that the serum-free medium is superior for long-term culture of rat pancreatic islets.     

Premature targeting of a cell division protein to midcell allows dissection of divisome assembly in Escherichia coli

Cell division in Escherichia coli requires the recruitment of at least 10 essential proteins to the bacterial midcell. Recruitment of these proteins follows a largely linear dependency pathway in which depletion of one cell division protein leads to the absence from the division site of "downstream" proteins in the pathway. Analysis of events that underlie this pathway is complicated by the fact that a protein's ability to recruit "downstream" proteins is dependent on its own recruitment by "upstream" proteins. Hence, one cannot separate the individual contributions of various upstream proteins to any specific recruitment step. Here we present a method--premature targeting--for bypassing the normal localization requirements of a cell division protein and apply it to FtsQ, a protein recruited midway through the pathway. We fused FtsQ to the FtsZ-binding protein ZapA such that FtsQ was targeted to FtsZ rings independently of proteins FtsA and FtsK, which are normally required for FtsQ localization. Analysis of the resulting ZapA-FtsQ fusion suggests that FtsQ associates with a large complex of cell division proteins and that premature targeting of FtsQ can restore localization of this complex under conditions in which neither FtsQ nor the associated proteins would normally be localized.     

Role of nerve and muscle factors in the development of rat muscle spindles

The soleus muscles of fetal rats were examined by electron microscopy to determine whether the early differentiation of muscle spindles is dependent upon sensory innervation, motor innervation, or both. Simple unencapsulated afferent-muscle contacts were observed on the primary myotubes at 17 and 18 days of gestation. Spindles, encapsulations of muscle fibers innervated by afferents, could be recognized early on day 18 of gestation. The full complement of spindles in the soleus muscle was present at day 19, in the region of the neuromuscular hilum. More afferents innervated spindles at days 18 and 19 of gestation than at subsequent developmental stages, or in adult rats; hence, competition for available myotubes may exist among afferents early in development. Some of the myotubes that gave rise to the first intrafusal (bag₂) fiber had been innervated by skeletomotor (α) axons prior to their incorporation into spindles. However, encapsulated intrafusal fibers received no motor innervation until fusimotor (γ) axons innervated spindles 3 days after the arrival of afferents and formation of spindles, at day 20. The second (bag₁) intrafusal fiber was already formed when γ axons arrived. Thus, the assembly of bag₁ and bag₂ intrafusal fibers occurs in the presence of sensory but not γ motor innervation. However, transient innervation of future bag₂ fibers by α axons suggests that both sensory and α motor neurons may influence the initial stages of bag₂ fiber assembly. The confinement of nascent spindles to a localized region of the developing muscle and the limited number of spindles in developing muscles in spite of an abundance of afferents raise the possibility that afferents interact with a special population of undifferentiated myotubes to form intrafusal fibers.     

Spatial deployment of attention within and across hemifields in an auditory task

Research on visual attention has demonstrated that covert attention can be focused on particular locations within one hemifield, but that a specific "meridian" cost may also be found for shifting attention between hemifields. These issues have received less consideration for audition, even though reliable behavioral measures for the effects of spatial attention on hearing are now available. We examined the spatial distribution of covert attention in an auditory task following spatially non-predictive peripheral auditory cues (which should induce exogenous attention shifts), or following symbolic central cues that predicted the likely location for the auditory target (to induce endogenous attention shifts). In both cases, we found that attention can be focused not only on one hemifield versus another, but also within one hemifield in an auditory task. However, there was no unequivocal evidence for a meridian effect in audition. Electronic Publication     

Colocalization of glutamate and glycine in bipolar cell terminals of the human retina

Human retinae from surgical specimens rapidly fixed in a glutaraldehyde/formaldehyde mixture were subjected to postembedding, immunogold immunocytochemistry of glutamate and glycine, and subsequently analysed in an electron microscope. The two amino acids were visualised in the same tissue sections by the use of two different gold particle sizes. All bipolar cell perikarya and terminals showed significant glutamate labelling with mean gold particle densities 3–4 times higher than those of the retinal, non-neural pigment epithelial and Müller cells. Bipolar cell terminals displayed significantly higher glutamate labelling density than the bipolar cell bodies, as would be expected of glutamatergic neurons. A subpopulation of the glutamate-immunolabelled bipolar cell bodies (18%) and terminals (32%) also exhibited strong glycine labelling (7–8 times that of pigment epithelial and Müller cells). These glutamate-glycine positive terminals established contacts with amacrine cell processes and ganglion cell dendrites and were localised almost exclusively at between 44% and 88% depth of the inner plexiform layer, indicating that they belong to the ON cone bipolar system. This subpopulation of terminals was endowed with significantly higher glycine labelling density than the glycine positive bipolar cell bodies. These results show that human bipolar cell terminals colocalise glutamate and glycine and provide the first direct demonstration of an enrichment of these two amino acids in the same presynaptic element.