Potent CD14-mediated signalling of human leukocytes by Escherichia coli can be mediated by interaction of whole bacteria and host cells without extensive prior release of endotoxin.

How invading microorganisms are detected by the host has not been well defined. We have compared the abilities of Escherichia coli and lipopolysaccharides (LPS) purified from these bacteria to prime isolated neutrophils for phorbol myristate acetate-stimulated arachidonate release, to trigger respiratory burst in 1% blood, and to increase steady-state levels of tumor necrosis factor alpha mRNA in whole blood. In all three assays, bacteria were > or = 10-fold more potent than equivalent amounts of LPS and could trigger maximal cellular responses at ratios as low as one bacterium per 20 to 200 leukocytes. Both E. coli and LPS-triggered responses were enhanced by LPS-binding protein and inhibited by an anti-CD14 monoclonal antibody and the bactericidal/permeability-increasing protein (BPI). However, whereas O polysaccharide did not affect the potency of isolated LPS, intact E. coli carrying long-chain LPS (O111:B4) was less potent than rough E. coli (J5). Furthermore, material collected by filtration or centrifugation of bacteria incubated under conditions used to trigger arachidonate release or chemiluminescence was 5- or 30-fold less active, respectively, than whole bacterial suspensions. Extracellular BPI (not bound to bacteria) inhibited bacterial signalling, but BPI bound to bacteria was much more potent. Taken together, these findings indicate that E. coli cells can strongly signal their presence to human leukocytes not only by shedding LPS into surrounding fluids but also by exposing endotoxin at or near their surface during direct interaction with host cells.     

Psychological factors that influence self-reported pain

Explored the relationship among the MMPI, the Beck Depression Inventory, and the pain dimensions from the McGill Pain Questionnaire. The instruments were administered to 30 male VA patients with histories of pain for longer than 3 months. Multiple regression analyses that investigated the relationship between depression and the pain measures found no statistically significant correlations. Additionally, the MMPI subscales were not related significantly to the sensory-discriminative pain scores, the cognitiveevaluative pain scores, the present pain intensity scores, the percent of body area in pain, or the total number of pain words endorsed. In contrast, the MMPI subscales were related significantly to the motivational-affective pain dimension and the miscellaneous pain dimension. In the motivational affective analysis, a significant positive correlation was found for the PT subscale, but a significant negative correlation was found for the Sc subscale. In the miscellaneous pain analysis, a significant positive correlation was found for the Hs subscale. The results are interpreted in the context of cognitive behavioral conceptualizations of chronic pain.     

Preforming of polydioxanone sheets for orbital wall fractures – A technical note

Introduction

Polydioxanone (PDS) sheets are commonly used in the treatment of orbital wall fractures. A potential drawback of PDS is that it may be difficult to adapt to the anatomy of the orbital walls. Therefore a study was conceived to test the feasibility of preforming PDS sheets.

Presenilin-dependent gamma-secretase activity modulates thymocyte development

In neuronal cells, presenilin-dependent gamma-secretase activity cleaves amyloid precursor proteins to release Abeta peptides, and also catalyzes the release of the intracellular domain of the transmembrane receptor Notch. Accumulation of aberrant Abeta peptides appears to be causally related to Alzheimer's disease. Inhibition of Abeta peptide production is therefore a potential target for therapeutic intervention. Notch proteins play an important role in cell fate determination in many different organisms and at different stages of development, for example in mammalian T cell development. We therefore addressed whether structurally diverse gamma-secretase inhibitors impair Notch function by studying thymocyte development in murine fetal thymic organ cultures. Here we show that high concentrations of the most potent inhibitors blocked thymocyte development at the most immature stage. In contrast, lower concentrations or less potent inhibitors impaired differentiation at a later stage, most notably suppressing the development of CD8 single-positive T cells. These phenotypes are consistent with an impairment of Notch signaling by gamma-secretase inhibitors and define a strict Notch dose dependence of consecutive stages during thymocyte development.     

Persistent infection of Muntiacus muntjak cells with adenovirus type 2 and abortive infection with adenovirus type 12

The Indian deer Muntiacus muntjak has the lowest chromosome number reported for mammals, six for the female and seven for the male animal. Adenovirus type 2 (Ad2) can replicate efficiently in these cells. When inoculated at low multiplicity, however, Ad2 establishes a persistent infection. The viral DNA persists in these cells apparently in a free form and replicates continuously. Tests for viral antigens and infectious center assays have revealed that about 1 to 2% of the cells produce Ad2. The persistent infection can be abolished by treating the infected cells with rabbit anti-Ad2 serum. As shown by the Southern blotting technique, the viral DNA is lost from the cells which were cured by antiserum treatment. Judging from the unabated replication of Sindbis virus or vesicular stomatitis virus in persistently Ad2-infected Muntiacus muntjak (M.m.) cells, the persistence of Ad2 is not accompanied by the production of interferon. Nor is there evidence for an Ad2-specific inhibitory factor, since persistently infected cells can be superinfected with high multiplicities of Ad2. Adenovirus type 12 (Ad 12) cannot multiply in M.m. cells. A very low level of replication of unit length Ad12 DNA can be detected. M.m. cells abortively infected with Ad12 continue to grow, and the viral DNA is eventually lost from the bulk of the cells. Ad12 infection leads to chromosomal abnormalities in M.m. cells. At 24 hr postinfection, 30–40% of the cells could be shown to be T antigen positive by immune fluorescence.     

An examination of the relationship between low vision and Charles Bonnet syndrome

Objective: In recent years, the Low Vision Clinic (LVC) appeared to have a large percentage of patients admitting to phantom vision (Charles Bonnet syndrome [CBS]). The objective of this study was to learn more about CBS from an ophthalmological perspective, as research has been conducted primarily by other specialists.Design: Large-scale prospective study using a cohort of low-vision and normal-vision subjects.Participants: Two hundred fifty-eight low-vision and 251 control subjects (with little or no vision loss) were enrolled.Methods: A comparison of visual acuity, ophthalmic conditions, eye treatments, medications, mental state, general health, socialization, etc., was undertaken, and other factors influencing the hallucinations were recorded.Results: CBS was present in 34% of LVC subjects and in <2% of the general population with little or no vision loss. Many subjects had unformed hallucinations; bright lights or spot-like images should not be overlooked because they could be determined to be hallucinations upon further questioning of the patient. CBS occurred in subjects with visual acuity from 20/40 to 20/1600; subjects were twice as likely to have CBS if their visual acuity was between 20/301 and 20/800.The prevalence of CBS did not differ significantly by cause of visual problem. Thirty-four percent of people were distressed about their initial hallucination; many did not consult a doctor for an explanation, and if they did, many did not receive an adequate explanation.Conclusions: This large-scale study shows that CBS is connected with a low vision level; thus, patients should be told about the common possibility of hallucinations.     

Differentiation of cytotoxic and vasogenic edema in a patient with reversible posterior leukoencephalopathy syndrome using diffusion-weighted MRI

In recent years reversible posterior leukoencephalopathy syndrome (RPLS) has become increasingly recognized. It represents an uncommon entity related to multiple pathologies, the most common being hypertensive crisis. The underlying pathophysiological mechanism is proposed to be one of vasogenic edema, without infarction; however, differentiation from cytotoxic edema can be crucial for therapeutic and clinical outcome. Diffusion-weighted magnetic resonance imaging (DWI), including calculation of the apparent diffusion coefficient (ADC), may be helpful for differentiation. We present a case of a healthy young woman in the 40th week of gestation, with no prior complications, who suddenly developed RPLS with vasogenic edema, which was differentiated with DWI and quantification of ADC. Follow-up cranial MRI showed complete remission. Pre-eclampsia could not be proven according to pathognomonic laboratory findings.