A broadly cross-protective monoclonal antibody binding to Escherichia coli and Salmonella lipopolysaccharides

During the last decade, episodes of sepsis have increased and Escherichia coli has remained the most frequent clinical isolate. Lipopolysaccharides (LPS; endotoxin) are the major toxic and antigenic components of gram-negative bacteria and qualify as targets for therapeutic interventions. Molecules that neutralize the toxic effects of LPS are actively investigated. In this paper, we describe a murine monoclonal antibody (MAb; WN1 222-5), broadly cross-reactive and cross-protective for smooth (S)-form and rough (R)-form LPS. As shown in enzyme-linked immunosorbent assay and the passive hemolysis assay, WN1 222-5 binds to the five known E. coli core chemotypes, to Salmonella core, and to S-form LPS having these core structures. In immunoblots, it is shown to react with both the nonsubstituted core LPS and with LPS carrying O-side chains, indicating the exposure of the epitope in both S-form and R-form LPS. This MAb of the immunoglobulin G2a class is not lipid A reactive but binds to E. coli J5, an RcP+ mutant which carries an inner core structure common to many members of the family Enterobacteriaceae. Phosphate groups present in the inner core contribute to the epitope but are not essential for the binding of WN1 222-5 to complete core LPS. Cross-reactivity for clinical bacterial isolates is broad. WN1 222-5 binds to all E. coli clinical isolates tested so far (79 blood isolates, 80 urinary isolates, and 21 fecal isolates) and to some Citrobacter, Enterobacter, and Klebsiella isolates. This pattern of reactivity indicates that its binding epitope is widespread among members of the Enterobacteriaceae. WN1 222-5 exhibits biologically relevant activities. In vitro, it inhibits the Limulus amoebocyte lysate assay activity of S-form and R-form LPS in a dose-dependent manner and it neutralizes the LPS-induced release of clinically relevant monokines (interleukin 6 and tumor necrosis factor). In vivo, WN1 222-5 blocks endotoxin-induced pyrogenicity in rabbits and lethality in galactosamine-sensitized mice. The discovery of WN1 222-5 settles the long-lasting controversy over the existence of anti-core LPS MAbs with both cross-reactive and cross-protective activity, opening new possibilities for the immunotherapy of sepsis caused by gram-negative bacteria.     

Bovine petechial fever (Ondiri disease)

This paper describes an efficient computer method for generating three-dimensional (3-D) ultrasonic speckle patterns for sector scans of an annular array with dynamic focusing in both transmit and receive. Assuming random scatterers in an attenuating medium, the system synthesizes the waveform for each scan line using echo data received at all annular elements of the transducer when short pulses are transmitted by one annulus after another. The amount of echo data needed to synthesize one waveform is tremendously reduced by reducing the 3-D distributions of scatterers to line distributions and by representing scatterers on a small line segment by a single equivalent scatterer taking into account the two-way travel time differences. Furthermore, by a judicious 3-D arrangement of the scatterer lines and scan lines, it is possible to synthesize the waveform for a new scan line with negligible computation overhead. The waveforms of the scan lines are detected to obtain a B-mode image or speckle patterns. The patterns obtained on several differently-oriented image planes showed a good statistical agreement with experimentally obtained patterns.     

Hematopoietic stem cell transplantation for infantile osteopetrosis

Infantile osteopetrosis is a lethal disorder resulting from a severe defect in the ability of osteoclasts to resorb bone. The only therapy shown to be capable of providing lasting benefit is allogeneic hematopoietic stem cell transplantation (HCT). We report the outcome of 10 patients with infantile malignant osteopetrosis treated with HCT from an HLA A, B, DRB1 matched (n=6) or A or B locus mismatched (n=4) family member or unrelated donor at the University of Minnesota between 1978 and 1997. Eight of 10 patients achieved primary engraftment; secondary graft failure was seen in two patients. Five of 10 patients survive; three with full or partial donor chimerism and two with autologous hematological recovery. Transient or partial donor chimerism can be sufficient to correct the hematological manifestations of osteopetrosis. We recommend early referral for consideration of HCT with a related or unrelated donor as neurosensory manifestations of osteopetrosis are generally not reversible. Donor engraftment may be easier to achieve early in the course of the disease.     

Understanding community receptivity to water re-use: Ku-ring-gai Council case study.

This social research project investigated community receptivity to using rainwater and greywater as alternative domestic water sources. It was focused in the Ku-ring-gai local government area in northern Sydney, and involved a household questionnaire followed by community leader interviews and resident focus groups. Trends, such as a prolonged drought and increasing population, compound the current crisis and concern facing Sydney's available water supply. Substitution of domestic potable water has been promoted as part of the solution. The research results revealed that community receptivity was highest for external uses, such as watering gardens and flushing toilets, and progressively decreased with increasing personal contact. Receptivity to greywater reuse fell more rapidly with the community believing there was a higher health risk associated with its use. Gender and cultural background were revealed as significant variables and give insight into the design of strategies to target these demographic groups. This evidence provides a reliable stocktake of current receptivity revealing that the community has good awareness and positive association with water reuse for many household activities. This now needs to be harnessed through programs targeted at developing skills, resources and motivation for new water reuse practices and technologies across diverse social groupings.     

Correlations between the electronic state and mechanical properties of some transition metal compounds/alloys

It is observed that changes in the mechanical state of solids can alter their electronic state and vice versa. The d-state electrons in transition metal compounds/alloys are found to influence mechanical properties in a range of materials that include intermetallic compounds, hard metals, cryogenic alloys, etc. We have attempted to represent these effects graphically as a field map based on axes of the number of d-state electrons in the compounds. Specifically identifiable properties are found in different regions in this property field map.     

Shifts produced by mode filters on curved intensity contours

The author considers the shifts produced by mode filters on curved boundaries and contours. It is shown that these are similar to those produced by mean and median filters, the cases of linear intensity variations and of step edges being somewhat different and at opposite extremes of a continuum. Thus, shifts are intrinsic to basic neighbourhood averaging techniques, and can be avoided only by specially designed operators     

Latest Developments in the Batchwise Application of Hot-dyeing Reactive Dyes to Cellulosic Knitwear

A dyeing profile for a range of reactive dyes suitable for application to cellulosic knitwear is defined. Such a profile shows good level-dyeing, reproducibility and fastness properties together with potential for simplified dyeing processes.     

Finite element approach for the modal analysis of open-boundarywaveguides

A general finite element approach to computing the modes of open-boundary waveguides is presented. This efficient and robust scheme applies equally to situations with real and complex propagation constants. By using a localised boundary impedance condition, the approach preserves the sparsity of the global matrices. A comparison with the well established infinite element technique and the analysis of a 2-D leaky optical structure are given as examples     

Characterization of mutated transforming growth factor-beta s which possess unique biological properties

Transforming growth factor-beta (TGF-beta) is a potent regulator of cell growth and differentiation. On the basis of the crystal structure of TGF-beta 2, we have designed and synthesized two mutant TGF-beta s, TGF-beta 1 (71 Trp) and TGF-beta 1 (delta 69-73). Although both of these molecules inhibited the growth of Mv1Lu mink lung epithelial cells and LS1034 colorectal cancer cells, which are affected equally by TGF-beta 1 and TGF-beta 2, TGF-beta 1 (delta 69-73) was much less potent than TGF-beta 1 or TGF-beta 1 (71 Trp) at inhibiting the growth of LS513 colorectal cancer cells which are growth-inhibited by TGF-beta 1 but not TGF-beta 2. Both TGF-beta 1 (71 Trp) and TGF-beta 1 (delta 69-73) increased levels of mRNAs for fibronectin and plasminogen activator inhibitor with Mv1Lu cells, whereas only TGF-beta 1 (71 Trp) and not TGF-beta 1 (delta 69-73) up-regulated the mRNA level of carcinoembryonic antigen in LS513 cells. The expression level of carcinoembryonic antigen mRNA in LS1034 cells was not altered by either wild-type or mutant TGF-beta s. Receptor labeling experiments demonstrated that TGF-beta 1 (71 Trp) bound with high affinity to the cell-surface receptors of Mv1Lu, LS1034, and LS513 cells while TGF-beta 1 (delta 69-73) bound effectively to the receptors of Mv1Lu and LS1034 cells but much less to the receptors on LS513 cells.(ABSTRACT TRUNCATED AT 250 WORDS)