A simplified in vivo drug sensitivity test for malaria in the field

Using a derivative of the plasmid pBR322 we have tested the dimer catastrophe hypothesis of plasmid instability. Most of the theory was confirmed by our observations, but our data suggest that some of the quantitative aspects need modification. In a recF strain of Escherichia coli we estimated the difference in loss rate between the plasmid in the monomeric and the dimeric state to be a factor of 13-14 and the difference in the loss rate between the plasmid in the monomeric and the trimeric state to be a factor of 14-50. We were able to confirm that plasmid oligomers were heterogeneously distributed within a rec+ population, but we were unable to detect any pronounced difference in the level of growth inhibition exerted by the plasmid when in the monomeric, dimeric, or trimeric state. This leaves open the question as to whether runaway plasmid multimerization was prevented (i) by a small correlation between the inhibition of growth and the 'multimeric status' of the plasmid, (ii) by intramolecular homologous recombination, or (iii) whether the process of runaway multimerization is too slow to be recognized within the duration of the experiments, i.e. 200 generations of growth.     

Overestimate of vaccine coverage? New evidence from a survey in Pau da Lima]

To evaluate vaccination coverage in children 0 to 5 years of age, a cross-sectional study based on a household survey was carried out in 1992 in the Pau de Lima Health District, Salvador, Bahia, Brazil, using a cluster sampling technique. The district was subdivided into 30 small areas that were homogeneous with respect to socioeconomic characteristics. Information on the vaccination status of 385 children was obtained through verification of a vaccination card or campaign voucher, or, in the absence of these items, through verbal confirmation from the mother or other responsible person. Based on all the sources of information, the study found vaccination coverage rates in the entire age range of 69% for polio vaccine; 56% for DTP; 74% for measles vaccine; and 87% for BCG. These results suggest that rates obtained from routine records of the health services and vaccination campaigns may be overestimates. The authors discuss the implications of the low coverage rates found in the entire age group and especially among children under 1 year old.     

Differential production of IL-10 by T cells and monocytes of HIV-infected individuals: association of IL-10 production with CD28-mediated immune responsiveness

The present study determines the proportions of unmyelinated cutaneous axons at the dermal-epidermal junction in glabrous skin and of myelinated and unmyelinated axons in the sural and medial plantar nerves that immunostain for subunits of the ionotropic glutamate receptors. Approximately 20% of the unmyelinated cutaneous axon profiles at the dermal-epidermal junction immunostain for either N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), or kainate receptor subunits. These findings are consistent with previous observations that NMDA and non-NMDA antagonists ameliorate nociceptive behaviors that result from noxious peripheral stimulation. In the sural nerve, where the large majority of myelinated fibers are sensory, approximately half of the myelinated axon profiles immunostain for the NMDA receptor 1 (R1) subunit, 28% immunostain for the glutamate receptor 1 (GluR1) AMPA subunit, and 11% for the GluR5,6,7 kainate subunits. Even higher proportions immunostain for these receptors in the medial plantar nerve, a mixed sensory and motor nerve. In the sural nerve, 20% of the unmyelinated axon profiles immunostain for NMDAR1 and only 7% label for GluR1 or GluR5,6,7. Because the sural nerve innervates hairy skin, these data suggest that glutamate will activate a higher proportion of unmyelinated axons in glabrous skin than in hairy skin. Measurements of fiber diameters indicate that all sizes of myelinated axon profiles, including Adelta and Abeta, are positively labeled for the ionotropic receptors. The presence of glutamate receptors on large-diameter myelinated axons suggests that these mechanosensitive receptors, presumably transducing touch and pressure, may also respond to local glutamate and thus be chemosensitive.     

Vav regulates peptide-specific apoptosis in thymocytes

Homologies between vertebrate forebrain subdivisions are still uncertain. In particular the identification of homologs of the mammalian neocortex or the dorsal ventricular ridge (DVR) of birds and reptiles is still a matter of dispute. To get insight about the organization of the primordia of the main telencephalic subdivisions along the anteroposterior axis of the neural tube, a fate map of the dorsal prosencephalon was obtained in avian chimeras at the 8- to 9-somite stage. At this stage, the primordia of the pallium, DVR and striatum were located on the dorsal aspect of the prosencephalon and ordered caudorostrally along the longitudinal axis of the brain. Expression of homeobox-containing genes of the Emx, Dlx and Pax families were used as markers of anteroposterior developmental subdivisions of the forebrain in mouse, chick, turtle and frog. Their expression domains delineated three main telencephalic subdivisions in all species at the onset of neurogenesis: the pallial, intermediate and striatal neuroepithelial domains. The fate of the intermediate subdivisions diverged, however, between species at later stages of development. Homologies between forebrain subdivisions are proposed based on the conservation and divergence of these gene expression patterns.     

Purinoceptors: are there families of P2X and P2Y purinoceptors?

There has been an exponential growth in interest in purinoceptors since the potent effects of purines were first reported in 1929 and purinoceptors defined in 1978. A distinction between P1 (adenosine) and P2 (ATP/ADP) purinoceptors was recognized at that time and later, A1 and A2, as well as P2x and P2y subclasses of P1 and P2 purinoceptors were also defined. However, in recent years, many new subclasses have been claimed, particularly for the receptors to nucleotides, including P2t, P2z, P2u(n) and P2D, and there is some confusion now about how to incorporate additional discoveries concerning the responses of different tissues to purines. The studies beginning to appear defining the molecular structure of P2-purinoceptor subtypes are clearly going to be important in resolving this problem, as well as the introduction of new compounds that can discriminate pharmacologically between subtypes. Thus, in this review, on the basis of this new data and after a detailed analysis of the literature, we propose that: (1) P2X(ligand-gated) and P2Y(G-protein-coupled) purinoceptor families are established; (2) four subclasses of P2X-purinoceptor can be identified (P2X1-P2X4) to date; (3) the variously named P2-purinoceptors that are G-protein-coupled should be incorporated into numbered subclasses of the P2Y family. Thus: P2Y1 represents the recently cloned P2Y receptor (clone 803) from chick brain; P2Y2 represents the recently cloned P2u (or P2n) receptor from neuroblastoma, human epithelial and rat heart cells; P2Y3 represents the recently cloned P2Y receptor (clone 103) from chick brain that resembles the former P2t receptor; P2Y4-P2Y6 represent subclasses based on agonist potencies of newly synthesised analogues; P2Y7 represents the former P2D receptor for dinucleotides. This new framework for P2 purinoceptors would be fully consistent with what is emerging for the receptors to other major transmitters, such as acetylcholine, gamma-aminobutyric acid, glutamate and serotonin, where two main receptor families have been recognised, one mediating fast receptor responses directly linked to an ion channel, the other mediating slower responses through G-proteins. We fully expect discussion on the numbering of the different receptor subtypes within the P2X and P2Y families, but believe that this new way of defining receptors for nucleotides, based on agonist potency order, transduction mechanisms and molecular structure, will give a more ordered and logical approach to accommodating new findings. Moreover, based on the extensive literature analysis that led to this proposal, we suggest that the development of selective antagonists for the different P2-purinoceptor subtypes is now highly desirable, particularly for therapeutic purposes.     

Inhalation of volatile substances: an emerging threat to readiness?

This report details a fine-needle aspiration biopsy performed in the investigation of two right breast nodules in a patient with previous history of lumpectomy for infiltrating ductal carcinoma in the same breast 3 years before. Because the cytology was atypical for a mammary carcinoma and cells did not match the morphology of the previous breast carcinoma, a tissue biopsy was recommended, revealing the presence of metastasis from a previously silent primary renal-cell carcinoma. This report illustrates not only how metastatic lesions in the breast can masquerade clinically as a primary carcinoma but also the necessity for the cautious approach to interpreting the fine-needle aspiration biopsy of these lesions. Furthermore, essential guidelines necessary to distinguish primary from metastatic lesions in the breast are presented.