Structure of the MscL homolog from Mycobacterium tuberculosis: a gated mechanosensitive ion channel

Mechanosensitive ion channels play a critical role in transducing physical stresses at the cell membrane into an electrochemical response. The MscL family of large-conductance mechanosensitive channels is widely distributed among prokaryotes and may participate in the regulation of osmotic pressure changes within the cell. In an effort to better understand the structural basis for the function of these channels, the structure of the MscL homolog from Mycobacterium tuberculosis was determined by x-ray crystallography to 3.5 angstroms resolution. This channel is organized as a homopentamer, with each subunit containing two transmembrane alpha helices and a third cytoplasmic alpha helix. From the extracellular side, a water-filled opening approximately 18 angstroms in diameter leads into a pore lined with hydrophilic residues which narrows at the cytoplasmic side to an occluded hydrophobic apex that may act as the channel gate. This structure may serve as a model for other mechanosensitive channels, as well as the broader class of pentameric ligand-gated ion channels exemplified by the nicotinic acetylcholine receptor.     

Short-term results of scleral intraocular lens fixation in children

PURPOSE: To study the safety and efficacy of scleral intraocular lens (IOL) fixation in children. SETTING: A university practice. METHODS: This retrospective review evaluated the results and complications in 6 consecutive eyes of 3 children who had anterior vitrectomy, with or without lensectomy, and scleral IOL fixation to correct ectopia lentis or aphakia. RESULTS: At a mean follow-up of 17.3 months (range 13 to 21 months), all eyes had a stable and well-positioned posterior chamber IOL and good visual improvement. The only complication was asymptomatic pupillary capture of the IOL in 3 eyes. Reversal of the pupillary capture was achieved by pupil dilation with the patient in a supine position. CONCLUSIONS: The preliminary results of scleral IOL fixation in children are encouraging. The procedure's application in well-selected cases can be considered. However, its long-term safety and efficacy must be further assessed through studies with larger sample sizes and a longer follow-up.     

Practical suggestions in diagnosing metachromatic leukodystrophy in probands and in testing family members

BACKGROUND: Echographic biometry of the ocular axial length is a helpful criterion in diagnosis and follow-up of primary congenital glaucoma. However, quantitative assessment of ocular growth following successful primary glaucoma surgery in the first year of life is hardly to find in literature. PATIENTS AND METHODS: In 36 eyes from 21 patients (mean age 4.4 +/- 2.4 months) with primary congenital glaucoma Ascan biometry was performed under general anesthesia before and 7.2 +/- 4.2 months following successful primary glaucoma surgery and retrospectively summarized. RESULTS: Preoperative axial length was 21.7 +/- 2.5 mm, postoperative axial length was 22.4 +/- 1.6 mm. Ocular growth was significantly stronger in eyes with a preoperative axial length < 20 mm (p = 0.0012) and in children younger than 3 months at surgery (p = 0.0004). CONCLUSIONS: Preoperative axial length and age are basic factors for the interpretation of ocular growth following glaucoma surgery in primary congenital glaucoma. Temporary cessation of ocular growth is a frequent finding after successful pressure-reducing surgery in eyes with axial length > 22 mm and in children aged 3 months or older.     

A potent and selective inhibition of parainfluenza 1 (Sendai) virus by new 6-oxiranyl-, 6-methyloxiranyluracils, and 4(3H)-pyrimidinone derivatives

Several new 6-oxiranyl-, 6-methyloxiranyluracils, and pyrimidinone derivatives, synthesized by the lithiation-alkylation sequence of 1,3,6-trimethyluracil, 1,3-dimethyl-6-chloromethyluracil, and 2-alkoxy-6-methyl-4(3H)-pyrimidinones, showed a potent and selective antiviral activity against the parainfluenza 1(Sendai) virus replication.     

Pediatric central nervous system tumors

Numerous collagenous structures must be reconstituted following injury to the skin in order to return function to this tissue. The basement membrane zone, vascular basement membranes, and the dense connective tissue of the dermis are examples of structures that contain a number of different collagen types and that may need replacement following injury. In addition, a scar is deposited at the site of damage in order to substitute for elements lost in the trauma and for elements that cannot be successfully replaced. Clearly, cells resident within the different compartments of the skin are able to synthesize and deposit collagen to reform these multiple structures. However, accumulating experimental evidence suggests that in addition to these resident cells, blood-borne cells may be responsible for the deposition of a portion of the newly synthesized collagen. Studies from this laboratory point to the activated monocyte as a potential source of collagen in the wound environment. Given the dynamics of the process, the hypothesis is proposed that during normal wound healing, the activated monocyte is a source of collagen essential for the rapid formation of a provisional matrix conducive for the subsequent formation of granulation tissue. Collagen synthesis also occurs by expanded populations of resident cells, under the influence of inflammatory cell-derived mediators, which results in the major accumulation of collagen during normal wound repair. However, if a chronic inflammatory state is initiated, the activated monocytes may remain in sufficient numbers to deposit collagen leading to a pathological lesion.     

Tetrachromacy, oil droplets and bird plumage colours

Survival rates in childhood cancer now approach approximately 65%, depending on the specific cancer. Success has been achieved through the use of increasingly aggressive treatments (chemotherapy, radiotherapy, bone-marrow transplantation). These are now recognised to be associated with a range of physical late effects, including problems associated with growth and endocrine function, sensory function, fertility, liver, cardiac, and kidney damage. Recognition of these physical late effects raises the issue of related problems in psychological, educational, and behavioural functioning. There is considerable evidence to suggest that children who are younger on diagnosis are more at risk in terms of cognitive and behavioural late effects compared with those who are diagnosed later. Cancer remains a rare disease in children and consequently only those professionals attached to centres specialising in the care of children with cancer are likely to receive a significant number of referrals. It is important to establish a psychological support service as an integral part of long-term care in order to (a) establish more accurately the incidence of social and psychological late effects and (b) offer advice to the individual about the possible long-term effects of cancer treatment on future health, social, and employment prospects.     

Early preferential stimulation of gamma delta T cells by TNF-alpha

Although recent findings indicate that gamma delta T cells influence both early innate and Ag-specific adaptive host responses, it has remained unclear what triggers gamma delta T cell reactivity. Investigating very early T cell activation in mouse and human models of bacterial infection, we measured CD69 expression as an indicator of early cellular activation. Both murine alpha beta and gamma delta T cells responded polyclonally to systemic bacterial infections, and to LPS. However, gamma delta T cells responded more strongly to the bacteria and to LPS. In vitro LPS-stimulated human T cells showed a similar differential response pattern. We identified TNF-alpha as mediator of the early differential T cell activation, and of differential proliferative responses. The stronger response of gamma delta T cells to TNF-alpha was correlated with higher inducible expression levels of TNF-Rp75. Among unstimulated splenocytes, more gamma delta T cells than alpha beta T cells expressed CD44 at high levels. The data suggest that TNF-Rp75 determines the differential T cell reactivity, and that most gamma delta T cells in the normal spleen are present in a presensitized state. As TNF-alpha stimulates activated T cells, it may early preferentially connect gamma delta T cell functions with those of cells that produce this cytokine, including activated innate effector cells and Ag-stimulated T lymphocytes.