Is the spectacle lens jack‐in‐the‐box phenomenon really due to the lenses?

The calculation of the extent of the ring scotoma around positive lenses, as conventionally taught to students of clinical optics, indicates that the scotoma is of a significant size. Using knife-edge lenses this study shows that the calculations are invalid due to the finite size of the eye's entrance pupil and in many instances the scotoma is shown not to exist. The effect noticed in clinical practice is probably largely due to the frame and the edging techniques used which add to the refractive scotoma which is present with high powered lenses, large apertures and/or small pupil sizes.     

Invited review: Neuroprotective properties of certain beta-adrenoceptor antagonists used for the treatment of glaucoma.

Although it is known that ganglion cell death causes loss of vision in glaucoma, the pathogenesis of the disease is complex, probably involving an initial ischemic insult to the ganglion cell axons and glial cells with the ganglion cell bodies eventually being affected. It may therefore be necessary to blunt many stages in the pathogenesis of the disease to obtain a clinically effective neuroprotective strategy. In animal experiments, one cause of ganglion cell death in ischemia is an overactivation of glutamate receptors and a subsequent rise in intracellular levels of sodium and calcium ions as well as a generation of reactive oxygen species. In contrast, optic nerve death in ischemia is mainly caused by an influx of sodium and reversal of the sodium/calcium exchanger, which leads to a rise in intracellular calcium. Thus, a substance that reduces the influx of sodium will protect the ganglion cell axon, and if it also reduces calcium influx and/or acts as an antioxidant it will protect the ganglion cell body in addition. Of all antiglaucoma drugs, only beta-blockers have both calcium and sodium channel blocking activity, with betaxolol being the most efficacious of those analyzed. In addition, of the tested ophthalmic beta-blockers only metipranolol has powerful antioxidant properties. Moreover, laboratory studies on rats have shown that topically applied beta-blockers attenuate ischemic injury to ganglion cells by mechanisms that do not appear to involve an action on beta-receptors. Thus, of the substances used to lower intraocular pressure in glaucoma, beta-blockers have unique additional characteristics that also give them the capacity to act as neuroprotectants.     

Laying the Cytotaxonomic Foundations of a New Model Grass, Brachypodium distachyon (L.) Beauv.

Brachypodium distachyon is a ubiquitous, temperate grass species which is being developed and exploited as an alternative model to rice, in order to gain access to important syntenic regions of the genomes of less tractable relatives such as wheat. As part of this initiative, this paper describes for the first time the cytotaxonomy of members of the polyploid series of this species, and challenges the assumption that the series evolved simply by chromosome doubling. In situ hybridization using genomic DNA probes and rDNA markers uncovers a hybrid origin of several of the polyploid ecotypes, and sheds light upon the complex evolution of this species and its close relatives.     

Maturation of myocardial capillaries in the fetal and neonatal rat: An ultrastructural study with a morphometric analysis of the vesicle populations

The ultrastructural morphology of the cellular and extracellular components of the developing myocardial capillary wall—from the 16-day-gestation fetus of the rat to the 21-day neonate—was examined. A morphometric analysis of plasmalemmal vesicles and of coated vesicles and pits of capillary endothelial cells was performed during the same developmental period. As the lateral extensions of the capillary endothelial cells change from irregular to regular in their thickness during development, there is an increase in the number of plasmalemmal vesicles and a progression from clusters of plasmalemmal vesicles to a uniform distribution in the endothelial cell. The ratio of vesicles which are open to the luminal front, which are “free” in the cytoplasm, or which are open to the abluminal front of the endothelial cell was consistent throughout development. The numerical density of plasmalemmal vesicles demonstrates a gradual and significant increase. In contrast, the numbers of coated vesicles and pits are variable within a very narrow range, and no pattern of increase or decrease is discernible during development. Similarly, there is no change in interendothelial cell junctions, which consist of occluding and primitive adhesive junctional types, during development. The lamina densa of the basal lamina gradually develops from discontinuous, patchy densities along the abluminal surface of the endothelial cells to a continuous and distinct layer by 21 days gestation. The presence of the proteoglycan species in the developing basal lamina was assessed with the cationic dye ruthenium red (RR), and the appearance of RR-marked proteoglycans was found to parallel the appearance of lamina densa material. The RR sites appear discontinuously in patches; and later, the RR sites appear in a continuous and regular planar lattice in the lamina rara interna and externa at 21 days gestation. A complete array of RR-stainable anionic sites outside a continuous lamina densa near birth indicates that the basal laminae of developing capillaries in the heart are morphologically, and in part biochemically, mature by the end of the first neonatal week. Our results show that the endothelial cells and the subtending basal lamina of myocardial capillaries gradually mature morphologically during the final days of gestation and the first neonatal week. The finding of tight junctions and small areas of vesicle concentration in fetal endothelial cells could indicate that sites of permeability are limited early in myocardial capillary development and that these vesicular sites increase as gestation proceeds and as the myocardial capillaries mature.     

Association of tuberculin-boosted antibody responses with pathology and cell-mediated immunity in cattle vaccinated with Mycobacterium bovis BCG and infected with M. bovis

Vaccine development and our understanding of the pathology of bovine tuberculosis in cattle would be greatly facilitated by definition of the immunological correlates of protection and/or pathology. In this study we analyzed humoral immune responses in Mycobacterium bovis BCG-vaccinated and control cattle (in particular, the relationship between the intradermal comparative tuberculin skin test and serum immunoglobulin G [IgG] responses) against a range of mycobacterial antigens (MPB59, MPB64, MPB70, MPB83, ESAT-6, CFP-10, Acr1, and PstS-1) by multiantigen print immunoassay and conventional enzyme-linked immunosorbent assay. Following M. bovis infection, the comparative tuberculin skin test strongly boosted IgG, IgG1, and IgG2 antibody responses, particularly against MPB83 and MPB70, in unvaccinated cattle but failed to boost these responses, or did so only weakly, in BCG-vaccinated calves. In addition, the skin test-induced increases in MPB83-specific IgG responses correlated positively with bacterial loads and ESAT-6-induced in vitro gamma interferon responses. In conclusion, both the negative correlation of skin test-enhanced MPB83-specific antibody responses with BCG-induced protection and their positive correlation with bacterial loads can serve as useful markers for vaccine efficacy after challenge.     

Gamma interferon responses induced by a panel of recombinant and purified mycobacterial antigens in healthy,non-mycobacterium bovis BCG-vaccinated Malawian young adults

We have previously shown that young adults living in a rural area of northern Malawi showed greater gamma interferon (IFN-gamma) responses to purified protein derivatives (PPD) prepared from environmental mycobacteria than to PPD from Mycobacterium tuberculosis. In order to define the mycobacterial species to which individuals living in a rural African population have been exposed and sensitized, we tested T-cell recognition of recombinant and purified antigens from M. tuberculosis (38 kDa, MPT64, and ESAT-6), M. bovis (MPB70), M. bovis BCG (Ag85), and M. leprae (65 kDa, 35 kDa, and 18 kDa) in >600 non-M. bovis BCG-vaccinated young adults in the Karonga District of northern Malawi. IFN-gamma was measured by enzyme-linked immunosorbent assay (ELISA) in day 6 supernatants of diluted whole-blood cultures. The recombinant M. leprae 35-kDa and 18-kDa and purified native M. bovis BCG Ag85 antigens induced the highest percentages of responders, though both leprosy and bovine tuberculosis are now rare in this population. The M. tuberculosis antigens ESAT-6 and MPT64 and the M. bovis antigen MPB70 induced the lowest percentages of responders. One of the subjects subsequently developed extrapulmonary tuberculosis; this individual had a 15-mm-diameter reaction to the Mantoux test and responded to M. tuberculosis PPD, Ag85, MPT64, and ESAT-6 but not to any of the leprosy antigens. We conclude that in this rural African population, exposure to M. tuberculosis or M. bovis is much less frequent than exposure to environmental mycobacteria such as M. avium, which have antigens homologous to the M. leprae 35-kDa and 18-kDa antigens. M. tuberculosis ESAT-6 showed the strongest association with the size of the Mantoux skin test induration, suggesting that among the three M. tuberculosis antigens tested it provided the best indication of exposure to, or infection with, M. tuberculosis.     

Action naming with impaired semantics: Neuropsychological evidencecontrasting naming and reading for objects and verbs

We contrast naming from pictures, and reading words, for objects and verbs (actions relating to the objects) in a patient with a large, posterior left-hemisphere lesion. We present evidence for spared picture naming for verbs relative to objects, whilst the opposite pattern of sparing occurred in reading. Objects were also spared relative to verbs in tasks requiring that written words be matched to either pictures or auditory words, in the presence of semantically related or unrelated distractors. We conclude that verb semantics were more impaired than semantic knowledge for objects, and that the better semantic knowledge for object names supported word reading. With pictures, however, action verb retrieval was maintained through a nonsemantic route from vision to action, or though preserved right-hemisphere "action semantics."     

Immunology of Diseases Associated with Malassezia Species

Malassezia species are members of the human cutaneous commensal flora, in addition to causing a wide range of cutaneous and systemic diseases in suitably predisposed individuals. Studies examining cellular and humoral immune responses specific to Malassezia species in patients with Malassezia-associated diseases and healthy controls have generally been unable to define significant differences in their immune response. The use of varied antigenic preparations and strains from different Malassezia classifications may partly be responsible for this, although these problems can now be overcome by using techniques based on recent work defining some important antigens and also a new taxonomy for the genus. The finding that the genus Malassezia is immunomodulatory is important in understanding its ability to cause disease. Stimulation of the reticuloendothelial system and activation of the complement cascade contrasts with its ability to suppress cytokine release and downregulate phagocytic uptake and killing. The lipid-rich layer around the yeast appears to be pivotal in this alteration of phenotype. Defining the nonspecific immune response to Malassezia species and the way in which the organisms modulate it may well be the key to understanding how Malassezia species can exist as both commensals and pathogens.