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S J Armstrong

Publications and source records attributed to S J Armstrong.

At least 37 records · Page 2Linked to original sources
PubMed1997

Neutralization titres of HIV-1-specific monoclonal antibodies vary according to the batch of primary human peripheral blood lymphocytes, but do not vary coordinately.

Human peripheral blood lymphocytes (PBL) were collected from five healthy adults under standard conditions and on a number of different occasions, and used in neutralization assays of human immunodeficiency virus type 1 (HIV-1) strain IIIB with three monoclonal antibodies (mAbs). Variations in neutralization titre were observed with different batches of PBLs with, for example, titres of ICR39.3b ranging from 1/10 to over 1/40000. However titres were as high, or higher, in PBLs than in C8166 cells (a human CD4+ T lymphoblastoid cell line) in 82% (28/34) of tests made. Most surprising was that neutralization by the three mAbs did not vary coordinately. In one batch of PBLs the neutralization titre of one of the mAbs might be increased while that of another mAb did not increase, or decrease. Thus PBLs could not be described as giving high or low levels of neutralization without reference to a specific mAb. This was not an assay problem as infectivity titres were relatively constant (varying by 1 to 1.4 fold with respect to C8166 cells), and neutralization titres were reproducible with the same batch of frozen PBLs over a three month period. Only one donor gave consistently low neutralization titres (defined here as 1/200; 2/2 batches tested) with all three mAbs, but all other donors gave similarly low titres with one of their batches of PBLs. The non-coordinate variation in neutralization titre indicates the advisability of using antibodies of several different specificities in any kind of preventive or therapeutic immunity.

Adult↗
PubMed1997

Cytological characterization of four meiotic mutants of Arabidopsis isolated from T-DNA-transformed lines.

A secondary screen of the Feldmann collection of T-DNA transformed Arabidopsis lines identified several meiotic mutants. We used a spreading technique combined with DAPI staining in a detailed cytogenetic analysis of meiotic chromosome behaviour in four of these mutants, all of which are putatively T-DNA tagged and therefore candidates for molecular and functional analysis of the mutated genes. Two of them are defined as 'synaptic' mutants, showing greatly reduced association of homologous chromosomes at metaphase I: one is asynaptic, showing failure of synapsis during prophase I, whereas the other is desynaptic and is characterized by normal but non-maintained synapsis. Another mutant is defective in meiotic cell cycle control and undergoes a third meiotic division, resembling a second division but without an additional round of chromosome duplication. A further mutant shows meiosis-limited chromosome disruption, resulting in extensive chromosome fragmentation combined with other defects. All four mutants experience very irregular chromosome distribution during the meiotic divisions, resulting in abnormal numbers and/or sizes of microspores, with resulting reduced fertility.

Arabidopsis↗
PubMed1996

Relationship between physical signs of elbow dysplasia and radiographic score in growing Rottweilers.

OBJECTIVE: To examine the relationship between physical signs of elbow dysplasia and radiographic appearance of the elbow joints in growing dogs. DESIGN: Prospective study. ANIMALS: 55 Rottweiler pups. PROCEDURE: Owners of clinically normal Rottweiler pups were contacted through breed clubs in 3 Australian states and asked to participate in the study. All those offering to participate were included. PROCEDURE: The first physical examination was performed when pups were 3 months old and included a lameness evaluation and palpation of the elbow joints. Physical examinations were repeated when pups were 5, 6, 9, and 12 months old. Radiographs of the elbows were obtained at 6 and 12 months. Relationships among lameness, decreased range of movement, signs of pain, and radiographic data related to elbow dysplasia were examined. RESULTS: Elbow dysplasia caused clinical lameness in only 3 dogs but 57% of dogs developed radiographic signs of elbow dysplasia by 12 months of age. A grade-2 radiographic score at 12 months of age was significantly associated with clinical elbow dysplasia. CLINICAL IMPLICATIONS: Elbow dysplasia has a prevalence of > 50% in certain breed populations. This study supports radiographic screening at 12 months of age, accompanied by physical examination to detect clinical elbow dysplasia.

Age Factors↗
PubMed1996

Two neutralizing anti-V3 monoclonal antibodies act by affecting different functions of human immunodeficiency virus type 1.

Monoclonal antibody (MAb) ICR41.1i (rat IgG2a) is specific for a conformation-dependent epitope of human immunodeficiency virus type 1 (HIV-1) V3 , and MAb F58 (mouse IgG1) recognizes the peptide IXXGPGR, at the tip of the V3 loop. Both MAbs neutralized HIV-1 strain IIIB in C8166 and HeLa-T4(CD4) cells. Neutralization by either MAb did not inhibit attachment of virus to target cells as determined by FACS analysis, ELISA or immunofluorescence, and such attachment was absolutely dependent on the availability of CD4 molecules. F58 inhibited virus-induced cell-cell fusion, and reduced internalization of virions in direct proportion to neutralization. In contrast, ICR41.li had no effect on HIV-1-mediated cell fusion or on internalization of virus. It was concluded that MAb F58 neutralized infectivity by inhibiting fusion of the virus with the cell and internalization of the viral core, and that ICR41.1i neutralized by inhibiting a post-fusion-internalization event. The possible mechanism by which a neutralizing antibody binds to the V3 loop and affects the function(s) of structures inside the virion is discussed. Lastly, postattachment neutralization (PAN) was investigated. F58 mediated PAN at 21 degrees C and 35 degrees C. However, ICR41.1i gave PAN at 21 degrees C but not at 35 degrees C, suggesting that a temperature-dependent event affecting the V3 loop had abrogated neutralization. Overall, it appears that antibodies to different epitopes within the V3 loop neutralize by affecting very different functions of the virus.

Animals↗
PubMed1996

Varying temperature-dependence of post-attachment neutralization of human immunodeficiency virus type 1 by monoclonal antibodies to gp 120: identification of a very early fusion-independent event as a neutralization target.

Neutralization of human immunodeficiency virus type 1 by adding antibody after the virus has attached to the host cell (post-attachment neutralization:PAN) was investigated using three rat monoclonal antibodies (MAbs) directed against the outer domain of the membrane protein, gp 120. Two of the MAbs are specific for the CD4-binding site region and one for the V3 loop. MAb ICR39.13g (CD4-binding site region-specific; IgG2b) effected PAN efficiently at temperatures from 4 to 35 degree C. MAb ICR41.1i (V3 loop-specific; IgG2c) effected PAN only at temperatures of 24 degree C and below. This suggests that its V3 epitope is masked by a change in gp 120 which occurs at temperatures > or = 26 degree C, or that the virion function which is inhibited by ICR41.1i and is responsible for neutralization has already operated at > or = 26 degree C. Resistance to neutralization by ICR41.1i occurred within 20 min of shifting the temperature up to 35 degree C. Finally, MAb ICR39.3b (CD4-binding site region-specific; IgG2b) did not give PAN at any temperature, indicating that neutralization can only occur if this MAb binds virus before it attaches to the cell. Thus, these studies identify at least one novel fusion-independent event, the neutralization target of a V3 MAb, which occurs very early in the initial stages of virus-cell interaction.

Animals↗
PubMed1995

Topographical variation within the articular cartilage and subchondral bone of the normal ovine knee joint: a histological approach.

Topographical variation in the articular cartilage and subchondral bone of the normal ovine knee was examined using histological techniques. The articular cartilage was examined grossly, then histological sections were cut and the cartilage thickness and chondrocyte density were measured. Bone mineral density, thickness of the subchondral bone plate (SBP) and volume and surface histomorphometrical parameters and mineral apposition rate were calculated for the subchondral bone. It was found that the articular cartilage on the tibial plateaux was thicker, less cellular, and overlay a thicker SBP than that on the femoral condyles. Similarly, the cartilage in the medial joint compartments was thicker, less cellular and overlying a thicker less dense SBP than that in the lateral joint compartments. There was no variation in bone histomorphometric parameters or mineral apposition rate between regions. Biomechanical testing has shown that loading is not uniform throughout the normal human knee joint. The present results suggest that loading within the ovine knee is also nonuniform, with the central regions of the tibial plateaux bearing greater loads than the femoral condyles, and the medial joint compartment being loaded more than the lateral one. The articular cartilage and subchondral bone have adapted in order to best withstand these variations in loading. These histological findings, plus the topographical variations in cartilage biochemistry reported by Read et al. (Topographical variation in composition, PG-biosynthesis and swelling pressure of cartilages of loaded tibio-femoral joints (Abstract). Proceedings of the Combined Meeting of the Orthopaedic Research Societies of USA, Japan and Canada.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

XY chromosome behaviour in the germ-line of the human male: a FISH analysis of spatial orientation, chromatin condensation and pairing.

We have used multicolour fluorescence in situ hybridization to study the behaviour of the X and Y chromosomes in relation to a representative autosome, chromosome 1, on air-dried testicular preparations from normal fertile human males. In a proportion of Sertoli cells at interphase as well as spermatogonial metaphases there is an apparent selective undercondensation of the heterochromatic block of the long arm of the Y, which may be of functional significance with respect to Y-specific gene activity, initiating and maintaining spermatogenesis; we suggest that this may involve a mechanism similar to heterochromatin position-effect variegation in Drosophila. In the supporting Sertoli as well as pre-meiotic and leptotene cells the X and Y occupy relatively restricted domains at opposite poles of the nuclear membrane, while the chromosome 1 centromere regions are located interstitially and appear prealigned. The XY pairing and 'sex vesicle' formation comprises a complex series of spatial movement and differential condensation patterns. On the basis of these observations we propose that: the XIST/Xist gene, known to be involved in somatic X inactivation, imposes a chromatin reorganization leading to bending at the X-inactivation centre both at first meiotic prophase in males and in the soma in females; and the differential X and Y segments are protected from potentially deleterious meiotic exchanges by their separate spatial orientation. In addition, there is an indication that the timing of pairing and first meiotic segregation of the sex chromosomes is different, and precocious in comparison to the pairing and segregation of the autosomes, which may explain the high incidence of sex chromosome aneuploidy in sperm.

Animals↗
PubMed1993

Moderate exercise exacerbates the osteoarthritic lesions produced in cartilage by meniscectomy: a morphological study.

Unilateral medial meniscectomy was performed on two groups of sheep. At 1 week post-operatively, one group (N = 5) underwent a regimen of moderate walking exercise (24 km/week), while the other group (N = 5) received no exercise. Two groups (N = 6 and 8) of unoperated sheep were used as exercised and unexercised controls for the respective meniscectomized groups. Six months post-surgery all groups were sacrificed and their knee joints were examined macroscopically using established scoring systems. In both groups, meniscectomy induced cartilage and bone changes typical of early hypertrophic osteoarthritis. However, meniscectomized animals subjected to the exercise program developed more severe cartilage lesions and osteophytes than their unexercised counterparts. While the cell density in femoral cartilage of the meniscectomized and exercised group was similar to controls, that of the meniscectomized but unexercised animals was higher. We conclude form these data that in this animal model exercise exacerbated the lesions induced in articular cartilage by meniscectomy.

Animals↗
PubMed1992

Incidence and clinical significance of sesamoid disease in rottweilers.

A group of 55 rottweiler pups was studied from three to 12 months old to assess the incidence and clinical significance of disease involving the palmar metacarpal sesamoid bones. The results of physical examination were correlated with clinical signs of lameness and the results of radiographic examination of the forefeet. Twenty-one dogs became lame during the study and in 12 of them the lameness was attributable to sesamoid disease. However by 12 months of age, the incidence of sesamoid disease as assessed by radiographic changes in the sesamoid bones was 73 per cent (30 of 41 dogs). Six of the 12 dogs which were lame owing to sesamoid disease got better without specific treatment. It was concluded that sesamoid disease can result in clinical lameness in young rottweilers, but that subclinical disease is common.

Age Factors↗
PubMed1992

Review of the use of MRI in soft tissue lesions.

The MR images of 34 patients with soft tissue lesions were retrospectively evaluated to assess the accuracy of the technique in distinguishing benign from malignant lesions, and to assess the usefulness of various criteria in making this distinction. The overall sensitivity for the detection of malignancy was 75% with a specificity of 94%. Size of lesion was found to be a good criterion in predicting malignancy, lesion margin and signal intensity were less useful. The tissue type was determined in a few instances where signal characteristics were typical, notably lipomas and neural tumours, but this was not reliable and in most lesions the tissue of origin cannot be determined on MR imaging and biopsy is necessary.

Adolescent↗
PubMed1992

Mechanisms of neutralization of a nairovirus (Dugbe virus) by polyclonal IgG and IgM.

Dugbe virus is a member of the nairovirus genus of the Bunyaviridae. Purified polyclonal anti-Dugbe virus IgG, which neutralized greater than 99.5% of virus, reduced attachment of virus to BSC-1 cell monolayers by only 36%. A 100-fold lower concentration neutralized virus by 88%, and had no effect upon attachment. Neutralizing IgG did not affect the ability of Dugbe virus to be internalized by or to fuse with BSC-1 cells. This suggests that IgG neutralization occurs largely at a stage subsequent to primary uncoating. Purified polyclonal anti-Dugbe virus IgM neutralized infectivity and had no effect on the attachment of virus to cells, but inhibited internalization of virus by about 50%. Thus IgM neutralizes partly by interfering with entry of virus and partly by a post-entry event. Neutralization by intermediate concentrations of IgM was enhanced 20-fold in the presence of complement. At high concentrations of IgM, complement-dependent neutralization declined. This is probably due to IgM binding in a planar rather than crab conformation, which does not expose the complement binding sites. Aggregation occurred only at relatively low concentrations of immunoglobulin. Electron microscopy and reactivation of infectivity by vortexing suggested that aggregation makes only a minor contribution to neutralization by IgG or IgM.

Animals↗
PubMed1992

Neutralization of influenza virus by low concentrations of hemagglutinin-specific polymeric immunoglobulin A inhibits viral fusion activity, but activation of the ribonucleoprotein is also inhibited.

High concentrations of hemagglutinin-specific neutralizing polymeric monoclonal immunoglobulin A (IgA) inhibit attachment of the majority of type A influenza virus virions to cell monolayers and tracheal epithelium (H. P. Taylor and N. J. Dimmock, J. Exp. Med. 161:198-209, 1985; M. C. Outlaw and N. J. Dimmock, J. Gen. Virol. 71:69-76, 1990). A minority of virions attaches but is not infectious. Here, we report that a different mechanism operates when influenza virus A/Puerto Rico/8/34 (H1N1) is neutralized by low concentrations of monoclonal polymeric IgA or when A/fowl plague virus/Rostock/34 (H7N1) is neutralized by low concentrations of polyclonal rat secretory IgA. Under these conditions, neutralized virus attaches to cells and is taken up by them. However, upon entering the cell, the nucleoprotein (NP) of neutralized virus is found in the perinuclear cytoplasm, whereas NP from nonneutralized virus is concentrated in the nucleus itself. Further data show that the low-pH-mediated cell fusion activity of virions is inhibited by IgA in proportion to loss of infectivity. The possibilities that neutralization by low amounts of polymeric IgA is caused by inhibition of the virion fusion activity and that the aberrant distribution of NP from neutralized virus results from its failure to escape from the endosomal system were investigated by using A/PR/8/34 and the fusogenic agent polyethylene glycol (PEG) at pH 5.4. A/PR/8/34 attached to cells at 4 degrees C, with minimal internalization of the virus; treatment with PEG at pH 5.4 and 4 degrees C for 1 min led to infectious fusion of nonneutralized virus with the plasma membrane and, under these conditions, was more efficient than PEG at pH 7 or medium at pH 5.4. Neutralized virus which was attached to cells and treated with acidified PEG appeared to undergo primary and secondary uncoating, with its NP protein becoming concentrated in the nucleus and M1 becoming concentrated in the perinuclear cytoplasm. Although the distribution of NP and M1 was indistinguishable from infectious virus, infectivity was not restored. Thus, even when IgA-induced inhibition of fusion is reversed, virus is still neutralized. We suggest that infectious influenza virus undergoes an activation stage which may be the relaxation of the ribonucleoprotein structure needed to permit transcription or may be the removal of M1 bound to the ribonucleoprotein.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Imaging of soft tissue tumors.

The evaluation of many soft tissue lesions remains a diagnostic dilemma for both the radiologist and the clinician. In recent years MR imaging has emerged as the modality of choice for the assessment of soft tissue tumors, with well-documented advantages over CT and other imaging techniques.

Humans↗
PubMed1991

Rhabdomyosarcoma associated with familial adenomatous polyposis.

We report a case of a 16 year old girl with orbital rhabdomyosarcoma who during chemotherapy developed bloody diarrhoea. On investigation she was found to have multiple colonic polyps. Cytogenetic analysis has shown a pattern typical of familial adenomatous polyposis. We present a review of the literature concerning the associations of familial adenomatous polyposis. The association of familial adenomatous polyposis with rhabdomyosarcoma has not been previously reported.

Adenomatous Polyposis Coli↗
PubMed1991

Rat peritoneal neutrophils selectively relax vascular smooth muscle.

A vascular relaxing factor from oyster glycogen-elicited rat peritoneal neutrophils has been shown previously to possess a pharmacologic profile similar to that described for endothelium-derived-relaxing factor. The present experiments were designed to determine the in vitro tissue and species selectivity effects of the neutrophil-derived nitric oxide. Neutrophils (1 x 10(5) to 1 x 10(8) cells/10-ml organ chamber) were added to organ chambers filled with a physiological salt solution (37 degrees C; pH 7.4; 21% O2; 100 U/ml of superoxide dismutase) containing a ring or strip of an isolated tissue contracted with an appropriate contractile agent. Neutrophils caused relaxations in all vascular tissues tested, with the dog coronary artery being the most sensitive (IC50 approximately 1 x 10(5) cells), followed by the dog femoral artery, rabbit aorta and dog saphenous vein, respectively. In the rabbit fundic strip, approximately 1 x 10(7) cells were required to induce 50% relaxation, with 1 x 10(8) cells producing less than 35% relaxation in the dog, guinea pig and rat tracheas. In contrast, nitroprusside- and cromakalim-induced relaxations in all the smooth muscle tissues tested. The response to cromakalim was similar in all tissues with nitroprusside being more active in the vascular tissues. Methylene blue (1 x 10(-5) M) abolished the neutrophil induced relaxations in the rabbit aorta and dog femoral artery but had no effect on the responses to nitroprusside or cromakalim in the rabbit aorta, dog femoral artery or guinea pig trachea. Neutrophils, nitroprusside and cromakalim had limited effects on the spontaneously beating guinea pig right atria.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗