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1.  Melaena as the presenting symptom of gastric mucosal injury due to blunt abdominal trauma 
Blunt abdominal trauma is a common cause of admission to the typical trauma centre. Hollow viscus injury from blunt trauma, however, is unusual and rarely involves the stomach. A 15 year old boy sustained a bicycle handle bar injury to the abdomen and presented to the casualty department four days later with melaena. A computed tomography (CT) scan of the abdomen showed normal findings but endoscopy revealed two “kissing” areas of mucosal ulceration on the anterior and posterior wall of the gastric antrum. The patient received a blood transfusion for anaemia but was otherwise treated conservatively and made a full recovery. The authors believe this to be the first reported case of melaena as the primary presenting symptom of gastric ulceration secondary to blunt abdominal trauma. Diagnosis of hollow viscus injuries due to blunt abdominal trauma requires a high index of suspicion and thorough investigation, particularly if the presentation is delayed.
PMCID: PMC2564107  PMID: 16627828
blunt abdominal trauma; gastric ulceration; melaena
2.  The genome of the simian and human malaria parasite Plasmodium knowlesi 
Nature  2008;455(7214):799-803.
Plasmodium knowlesi is an intracellular malaria parasite whose natural vertebrate host is Macaca fascicularis (the ‘kra’ monkey); however, it is now increasingly recognized as a significant cause of human malaria, particularly in southeast Asia1,2. Plasmodium knowlesi was the first malaria parasite species in which antigenic variation was demonstrated3, and it has a close phylogenetic relationship to Plasmodium vivax​4, the second most important species of human malaria parasite (reviewed in ref. 4). Despite their relatedness, there are important phenotypic differences between them, such as host blood cell preference, absence of a dormant liver stage or ‘hypnozoite’ in P. knowlesi, and length of the asexual cycle (reviewed in ref. 4). Here we present an analysis of the P. knowlesi (H strain, Pk1(A+) clone5) nuclear genome sequence. This is the first monkey malaria parasite genome to be described, and it provides an opportunity for comparison with the recently completed P. vivax genome4 and other sequenced Plasmodium genomes6-8. In contrast to other Plasmodium genomes, putative variant antigen families are dispersed throughout the genome and are associated with intrachromosomal telomere repeats. One of these families, the KIRs9, contains sequences that collectively match over one-half of the host CD99 extracellular domain, which may represent an unusual form of molecular mimicry.
PMCID: PMC2656934  PMID: 18843368
3.  Survival in colorectal cancer: impact of body mass and exercise 
Gut  2006;55(1):8-10.
Is there a relationship between exercise and body composition prior to a diagnosis of colorectal cancer and survival afterwards?
PMCID: PMC1856384  PMID: 16344571
colorectal cancer; exercise; adiposity; survival; obesity
4.  Surgical strategies for necrotising enterocolitis: a survey of practice in the United Kingdom 
Background: Strategies for the surgical management of necrotising enterocolitis are various and controversial.
Objective: To characterise variation in surgical management of this disease across the United Kingdom.
Methods: Postal survey of 104 consultant paediatric surgeons with a 77% response rate.
Results: Duration of antibiotic treatment (median 10 days, range 6–14), time until the start of enteral feeding (median 10 days, range 4–21), and absolute indications for surgery all vary between surgeons. Peritoneal drainage is used by 95% of surgeons. Forty two percent use it in neonates of all weights, whereas 36% restrict its use to those <1000 g. Peritoneal drainage is used for stabilisation by 95% and as definitive treatment by 58%. At laparotomy, operative procedures include diverting jejunostomy, resection and stoma, resection with primary anastomosis, and "clip and drop". All procedures are used in infants of all weights except resection and primary anastomosis, which is used predominantly in larger infants (55% in <1000 g; 77% in >1000g; p = 0.005). Infants may be considered too unwell for peritoneal drainage by 11% of surgeons compared with 90% for laparotomy (p<0.0001).
Conclusions: There is considerable variation in surgical strategies for necrotising enterocolitis. Peritoneal drainage is used by most surgeons, with controversial indications and expectations. The use of resection and primary anastomosis is influenced by the weight of the neonate.
PMCID: PMC1721850  PMID: 15724040
5.  The genome of the social amoeba Dictyostelium discoideum 
Eichinger, L. | Pachebat, J.A. | Glöckner, G. | Rajandream, M.-A. | Sucgang, R. | Berriman, M. | Song, J. | Olsen, R. | Szafranski, K. | Xu, Q. | Tunggal, B. | Kummerfeld, S. | Madera, M. | Konfortov, B. A. | Rivero, F. | Bankier, A. T. | Lehmann, R. | Hamlin, N. | Davies, R. | Gaudet, P. | Fey, P. | Pilcher, K. | Chen, G. | Saunders, D. | Sodergren, E. | Davis, P. | Kerhornou, A. | Nie, X. | Hall, N. | Anjard, C. | Hemphill, L. | Bason, N. | Farbrother, P. | Desany, B. | Just, E. | Morio, T. | Rost, R. | Churcher, C. | Cooper, J. | Haydock, S. | van Driessche, N. | Cronin, A. | Goodhead, I. | Muzny, D. | Mourier, T. | Pain, A. | Lu, M. | Harper, D. | Lindsay, R. | Hauser, H. | James, K. | Quiles, M. | Babu, M. Madan | Saito, T. | Buchrieser, C. | Wardroper, A. | Felder, M. | Thangavelu, M. | Johnson, D. | Knights, A. | Loulseged, H. | Mungall, K. | Oliver, K. | Price, C. | Quail, M.A. | Urushihara, H. | Hernandez, J. | Rabbinowitsch, E. | Steffen, D. | Sanders, M. | Ma, J. | Kohara, Y. | Sharp, S. | Simmonds, M. | Spiegler, S. | Tivey, A. | Sugano, S. | White, B. | Walker, D. | Woodward, J. | Winckler, T. | Tanaka, Y. | Shaulsky, G. | Schleicher, M. | Weinstock, G. | Rosenthal, A. | Cox, E.C. | Chisholm, R. L. | Gibbs, R. | Loomis, W. F. | Platzer, M. | Kay, R. R. | Williams, J. | Dear, P. H. | Noegel, A. A. | Barrell, B. | Kuspa, A.
Nature  2005;435(7038):43-57.
The social amoebae are exceptional in their ability to alternate between unicellular and multicellular forms. Here we describe the genome of the best-studied member of this group, Dictyostelium discoideum. The gene-dense chromosomes encode ~12,500 predicted proteins, a high proportion of which have long repetitive amino acid tracts. There are many genes for polyketide synthases and ABC transporters, suggesting an extensive secondary metabolism for producing and exporting small molecules. The genome is rich in complex repeats, one class of which is clustered and may serve as centromeres. Partial copies of the extrachromosomal rDNA element are found at the ends of each chromosome, suggesting a novel telomere structure and the use of a common mechanism to maintain both the rDNA and chromosomal termini. A proteome-based phylogeny shows that the amoebozoa diverged from the animal/fungal lineage after the plant/animal split, but Dictyostelium appears to have retained more of the diversity of the ancestral genome than either of these two groups.
PMCID: PMC1352341  PMID: 15875012
6.  Adult midgut expressed sequence tags from the tsetse fly Glossina morsitans morsitans and expression analysis of putative immune response genes 
Genome Biology  2003;4(10):R63.
An expressed sequence tag (EST) project on the adult tsetse midgut, the major organ system for establishment and early development of trypanosomes has been undertaken. The most notable block of genes upregulated in response to trypanosome challenge are a series of Toll and Imd genes and a series of genes involved in oxidative stress responses.
Tsetse flies transmit African trypanosomiasis leading to half a million cases annually. Trypanosomiasis in animals (nagana) remains a massive brake on African agricultural development. While trypanosome biology is widely studied, knowledge of tsetse flies is very limited, particularly at the molecular level. This is a serious impediment to investigations of tsetse-trypanosome interactions. We have undertaken an expressed sequence tag (EST) project on the adult tsetse midgut, the major organ system for establishment and early development of trypanosomes.
A total of 21,427 ESTs were produced from the midgut of adult Glossina morsitans morsitans and grouped into 8,876 clusters or singletons potentially representing unique genes. Putative functions were ascribed to 4,035 of these by homology. Of these, a remarkable 3,884 had their most significant matches in the Drosophila protein database. We selected 68 genes with putative immune-related functions, macroarrayed them and determined their expression profiles following bacterial or trypanosome challenge. In both infections many genes are downregulated, suggesting a malaise response in the midgut. Trypanosome and bacterial challenge result in upregulation of different genes, suggesting that different recognition pathways are involved in the two responses. The most notable block of genes upregulated in response to trypanosome challenge are a series of Toll and Imd genes and a series of genes involved in oxidative stress responses.
The project increases the number of known Glossina genes by two orders of magnitude. Identification of putative immunity genes and their preliminary characterization provides a resource for the experimental dissection of tsetse-trypanosome interactions.
PMCID: PMC328452  PMID: 14519198
7.  Grading nuclear cataract: reproducibility and validity of a new method 
The British Journal of Ophthalmology  1999;83(10):1159-1163.
AIMS—To assess the reproducibility and validity of a new instrument for grading nuclear cataract—the laser slit lamp, by comparison with an established method of lens grading—the Lens Opacities Classification System III (LOCS III).
METHODS—62 volunteers (113 eyes) were examined on two occasions. At each visit, a video image of the anterior segment was captured with the laser slit lamp and stored digitally. A measure of lens opacity for each laser slit lamp image was calculated using image analysis software. Each lens was also photographed on both visits for LOCS III grading of nuclear colour and nuclear opalescence.
RESULTS—There was a linear increasing relation between the laser slit lamp measure of nuclear lens opacity and the LOCS III nuclear opalescence scores. The overall reproducibility of the laser slit lamp measurement was comparable with LOCS III (intraclass correlation coefficient of 95% (95% CI 92.9-96.5) for the laser slit lamp method; 97% (95% CI 95.6-97.9) for the LOCS III method). However, among healthy subjects, the reproducibility was lower (intraclass correlation for the laser slit lamp of 38.6% (95% CI 12.9-59.2) and 76.1% (95% CI 62.3-85.4) for LOCS III.
CONCLUSION—The laser slit lamp appears to give a valid measurement of nuclear cataract. The reproducibility of the instrument was high and similar to that of LOCS III. Modifications to the design would have to be made to improve its reproducibility among healthy subjects. It is simpler than other objective instruments, and could be useful in large scale studies of cataract.

PMCID: PMC1722807  PMID: 10502578
8.  Conservation of long-range synteny and microsynteny between the genomes of two distantly related nematodes 
Genome Biology  2002;3(10):research0057.1-research0057.14.
To assess whether the pattern of high rates of genome rearrangement, with a bias towards within-chromosome events is true of nematodes in general, genome sequence was used to compare the model Caenorhabditis elegans and the filarial parasite Brugia malayi. It is suggested that intrachromosomal rearrangement is a major force driving chromosomal organization in nematodes.
Comparisons between the genomes of the closely related nematodes Caenorhabditis elegans and Caenorhabditis briggsae reveal high rates of rearrangement, with a bias towards within-chromosome events. To assess whether this pattern is true of nematodes in general, we have used genome sequence to compare two nematode species that last shared a common ancestor approximately 300 million years ago: the model C. elegans and the filarial parasite Brugia malayi.
An 83 kb region flanking the gene for Bm-mif-1 (macrophage migration inhibitory factor, a B. malayi homolog of a human cytokine) was sequenced. When compared to the complete genome of C. elegans, evidence for conservation of long-range synteny and microsynteny was found. Potential C. elegans orthologs for II of the 12 protein-coding genes predicted in the B. malayi sequence were identified. Ten of these orthologs were located on chromosome I, with eight clustered in a 2.3 Mb region. While several, relatively local, intrachromosomal rearrangements have occurred, the order, composition, and configuration of two gene clusters, each containing three genes, was conserved. Comparison of B. malayi BAC-end genome survey sequence to C. elegans also revealed a bias towards intrachromosome rearrangements.
We suggest that intrachromosomal rearrangement is a major force driving chromosomal organization in nematodes, but is constrained by the interdigitation of functional elements of neighboring genes.
PMCID: PMC134624  PMID: 12372145
9.  Quantitation of IL-2Rp75 (CD122) expression on mononuclear cells in rheumatic disease. 
Annals of the Rheumatic Diseases  1996;55(11):844-847.
OBJECTIVE: To compare expression of the p75 chain of the interleukin-2 receptor (IL-2Rp75, CD122) on peripheral and synovial mononuclear cells in rheumatoid and non-rheumatoid inflammatory arthritis. METHODS: Peripheral blood (PBMC) and synovial (SFMC) mononuclear cells were isolated from subjects with rheumatoid arthritis (n = 16) and non-rheumatoid inflammatory arthritis (n = 12). PBMC were isolated from six healthy controls. Expression of CD122 was examined using indirect immunofluorescence and quantitative flow cytometry. RESULTS: There was no difference in IL-2Rp75 expression on PBMC from rheumatoid arthritis patients, non-rheumatoid arthritis patients, and controls. In subjects with rheumatoid arthritis there was no difference in IL-2Rp75 expression on PBMC and SFMC. However, in the non-rheumatoid arthritis group there was an increase in IL-2Rp75 expression on SFMC compared with PBMC (P = 0.0032). On SFMC there was a greater expression of IL-2Rp75 in non-rheumatoid arthritis than in rheumatoid arthritis (P = 0.0007). Expression was greater on CD8 positive cells and in subjects with shorter duration of disease. CONCLUSIONS: The p75 chain of the IL-2 receptor, an important T cell activation antigen, is not upregulated in synovial fluid. This appears to be a disease specific defect and provides further support for the concept of "frustrated" or incomplete T cell activation in this disease.
PMCID: PMC1010323  PMID: 8976644
10.  Expression of CD44 on rheumatoid synovial fluid lymphocytes. 
Annals of the Rheumatic Diseases  1995;54(7):566-570.
OBJECTIVES--To investigate the involvement of the adhesion molecule CD44 in the homing of lymphocytes to synovial tissue, by examining the density of expression and molecular mass of CD44 on rheumatoid synovial fluid lymphocytes. METHODS--Twenty patients with rheumatoid arthritis were studied. Peripheral blood and synovial fluid lymphocytes were isolated by Ficoll-Hypaque sedimentation. CD44 expression was analysed by two colour flow cytometry of CD3 positive T lymphocytes with calculation of mean fluorescence intensity. Expression of activation markers M21C5, M2B3, interleukin (IL)-2 receptor and transferrin receptor was quantitated. In addition, CD44 molecular mass was examined by Western blot in six patients. RESULTS--CD44 expression was markedly increased on synovial fluid T lymphocytes of rheumatoid patients relative to peripheral blood lymphocytes from the same individuals. CD44 molecular mass on peripheral blood mononuclear cells was 88 kDa, but that on synovial fluid lymphocytes was only 83 kDa. CD44 expression correlated significantly with expression of activation markers M21C5, M2B3, and the IL-2 receptor. CONCLUSIONS--Alterations in density of expression or of the molecular mass of CD44 could contribute to local tissue injury, either directly by facilitating adhesion, or indirectly through effects on other adhesion molecules.
PMCID: PMC1009936  PMID: 7545382
11.  Serum concentrations of soluble adhesion molecules in patients with colorectal cancer. 
British Journal of Cancer  1998;77(11):1857-1863.
The concentrations of the soluble adhesion molecules E-cadherin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were investigated in 48 patients with colorectal cancer before treatment, and their relation to clinical, histological and routine laboratory parameters was examined. Data were collected on tumour stage at presentation, presence and sites of metastatic disease, tumour pathology and results of routine laboratory tests. Serum concentrations of ICAM-1 and VCAM-1 were significantly elevated in the patients with colorectal cancer in comparison with a group of healthy subjects (P < 0.00001). Levels of circulating ICAM-1 and VCAM-1 were increased both in patients with local and those with metastatic disease. Although elevated in some patients soluble E-cadherin and E-selectin concentrations were not significantly elevated compared with the control group (P = 0.71 and P = 0.052 respectively). The levels of circulating ICAM-1 were significantly correlated with those of VCAM-1 and E-selectin. A correlation was also found between the serum concentrations of E-selectin and ICAM-1 and alkaline phosphatase, total white cell count and platelet count. VCAM-1 was positively correlated with age and negatively with degree of tumour differentiation and haemoglobin concentration. The biological implications and possible clinical relevance of these findings are discussed.
PMCID: PMC2150349  PMID: 9667659
13.  The role of CA-242 and CEA in surveillance following curative resection for colorectal cancer. 
British Journal of Cancer  1994;70(3):549-553.
This study was undertaken to evaluate the role of a new tumour marker, CA-242, alone or in combination with CEA in the practical management of colorectal cancer patients after potentially curative resection. A cohort of 149 patients who had undergone 'curative' surgery was followed up according to an intensive protocol in order to detect recurrent disease. Over a median tumour marker follow-up period of 24 months there were 25 recurrences in 24 patients. Both CEA and CA-242 alone detected half the local recurrences. The sensitivity of CEA was 84% for distant or mixed recurrence compared with 64% for CA-242. An abnormality of either CEA or CA-242 enabled detection of five out of six local recurrences and 17 out of 19 distant or mixed recurrences with a median lead time of 5 months for each marker. Both markers were elevated concurrently in only one local and 11 distant recurrences. While CA-242 alone is not superior to CEA, their combined use (either abnormal) has a high sensitivity (88%), specificity (78%) and negative predictive value (97%); this may be useful in reducing unnecessary investigations in follow-up programmes and as a guide to the initiation of further treatment for recurrent disease.
PMCID: PMC2033359  PMID: 8080745
14.  Muir-Torre syndrome: a variant of the cancer family syndrome. 
Journal of Medical Genetics  1994;31(8):627-631.
Muir-Torre syndrome is characterised by the association of sebaceous tumours of the skin with internal malignancy. In many instances there is a strong family history of cancer and the autosomal dominant mode of inheritance, tumour spectrum, and high incidence of synchronous and metachronous tumours show parallels with the cancer family syndrome or Lynch II syndrome. We report a five generation family with at least two persons displaying the Muir-Torre phenotype, while many other family members have had tumours consistent with cancer family syndrome. The majority of tumours are gastrointestinal, gynaecological, and urological, with several persons having multiple primaries. The prognosis appears to be better than would be expected. Sebaceous tumours are a marker for internal malignancy and should prompt a search for occult cancer in the individual person and family members. In documented Muir-Torre families, at risk persons should be entered into screening programmes similar to those used in the Lynch II syndrome.
PMCID: PMC1050025  PMID: 7815421
16.  Autoantibodies to recombinant lipocortin-1 in rheumatoid arthritis and systemic lupus erythematosus. 
Annals of the Rheumatic Diseases  1989;48(10):843-850.
Corticosteroids may mediate some of their anti-inflammatory effects via induction of a specific 38 kD protein, lipocortin-1. Autoantibodies to lipocortin-1 were measured by enzyme linked immunosorbent assay (ELISA) in 90 healthy subjects and in 63 patients with rheumatoid arthritis (RA), 36 with systemic lupus erythematosus (SLE), 26 with polymyalgia rheumatica, and 13 with chronic airways disease. Sixteen patients with RA receiving prolonged, high steroid doses (prednisolone greater than 7.5 mg/day) had raised IgM antilipocortin-1 levels, while 19 patients with RA untreated with steroids had normal levels. This association was independent of disease activity. In SLE, raised antilipocortin-1 levels were associated with active disease and were independent of steroid treatment. Antilipocortin-1 antibody levels were not raised in patients with polymyalgia rheumatica and chronic airways disease. Thus steroid treatment alone appears insufficient to induce antilipocortin-1 antibodies, unless an underlying autoimmune state is also present. In RA, antilipocortin-1 antibodies may impair anti-inflammatory actions of steroids and render some patients 'steroid resistant'.
PMCID: PMC1003892  PMID: 2554826
17.  Application of ribotyping for differentiating aeromonads isolated from clinical and environmental sources. 
We have investigated the usefulness of ribotyping for the differentiation of aeromonads isolated from five patients with gastroenteritis and from the source water, treatment plant, and distribution system of a small public water supply. Aeromonas hydrophila and Aeromonas caviae were isolated from fecal specimens preserved in Cary-Blair transport medium by using blood ampicillin agar or alkaline peptone water (pH 8.4) subcultured to blood ampicillin agar plates. A. hydrophila, Aeromonas sobria, and A. caviae were isolated from duplicate 100-ml water samples by the membrane filter technique by using ampicillin dextrin agar for quantitative determination of growth and alkaline peptone water enrichment for detection of the presence or absence of aeromonads below the detection limit of the membrane filter method. In addition, free chlorine residuals and pH values were determined for all water samples and heterotrophic plate counts and total and fecal coliform analyses were performed on them. Ribotyping patterns of aeromonads recovered from well 1, detention basin, sand filter, softener, and distribution samples were compared with those of the five clinical isolates. All patient strains were unique; however, identical ribotypes of A. hydrophila and A. sobria isolated from multiple sites in the water system indicated colonization of a well, sand filters, and the softener, with the potential for sporadic contamination of distribution water. Plant operational deficiencies were noted and corrected. Ribotyping can effectively differentiate otherwise indistinguishable strains of bacteria, thus providing a powerful tool for investigation of waterborne diseases and bacteriological problems within water treatment plants and distribution systems.
PMCID: PMC195707  PMID: 1622269
19.  More than meets the eye: a study of the time lost from work by patients who incurred injuries from corneal foreign bodies. 
A prospective study was carried out to establish the time lost from work due to corneal foreign body injury. Data were collected over a 5 month period on a total of 504 patients attending a busy district hospital eye casualty department. The median time lost through injury was 4 hours and 148 patients (30%) took no time off work. Corneal foreign bodies are known to be painful injuries but in spite of this few patients take more than half a day off work.
PMCID: PMC1042556  PMID: 1768665
20.  Olivopontocerebellar atrophy of neonatal onset and disialotransferrin developmental deficiency syndrome. 
Archives of Disease in Childhood  1991;66(9):1027-1032.
Two brothers presented with olivopontocerebellar atrophy of neonatal onset. The clinical features (failure to thrive, hypotonia, liver disease, effusions, and visual inattention) were similar to those of the four cases already reported, as were the necropsy findings of olivopontocerebellar atrophy, hepatic steatosis and fibrosis, and microcystic renal changes. The clinical similarities between this and the disialotransferrin developmental deficiency syndrome were noted. The characteristic abnormality of serum transferrin found in the latter syndrome was also found in the two cases reported here. We suggest that both syndromes are caused by the same, or related, defects in glycoprotein metabolism.
PMCID: PMC1793023  PMID: 1929507
21.  Lymphocytes bearing Fc gamma receptors in rheumatoid arthritis. IV. Increased numbers and activation of Facb-R+ cells after immunisation of healthy individuals. 
Annals of the Rheumatic Diseases  1986;45(11):925-931.
Mononuclear cells expressing Fc gamma receptors that form Facb rosettes are increased in the peripheral blood of patients with rheumatoid arthritis compared with controls. Healthy individuals with a positive skin response to tuberculin showed a marked increase in numbers of circulating Facb-R+ cells three days after challenge, returning to baseline after seven days. No response was observed in subjects showing a negative skin test. A similar increase in Facb-R+ cell numbers was measured after intramuscular injection of another specific antigen, tetanus toxoid. In addition to this enhancement of Facb-R+ cell numbers, evidence has been obtained that these cells are in an activated state postimmunisation as judged by acquisition of low density and increased expression of class II MHC antigens. Apparently identical changes in Facb-R+ cell numbers and activation may be induced in vitro either by culturing sensitised mononuclear cells with specific antigen for three days or by an overnight incubation of normal cells with gamma-interferon (gamma-IFN). By analogy, therefore, the increased numbers of Facb-R+ cells in patients with rheumatoid arthritis are probably induced by gamma-interferon generated as part of an antigen driven immune response. In this context it is interesting that patients with Felty's syndrome, in whom neutropenia increases susceptibility to infections leading to the possibility of further stimulation of the immune system by micro-organisms, have particularly high levels of circulating Facb-R+ cells.
PMCID: PMC1002021  PMID: 3098196
22.  Characterization of a suppressor factor that regulates phagocytosis by macrophages in murine cryptococcosis. 
Infection and Immunity  1989;57(6):1773-1779.
A T-suppressor factor which inhibits the phagocytic activity of a macrophage subset has been further characterized. This suppressor factor was first described for a murine model of cryptococcosis but was later found to be common to models of immunologic unresponsiveness. The suppressor factor was produced when suppressor cells were cultured in the presence of specific cryptococcal antigen. It could not be extracted from spleen cells and was not induced by antigen in cultures of lymph node cells. The suppressor factor was filtered through Amicon filters of 100-kilodalton (kDa) exclusion limit but was retained by filters excluding molecules of less than 50 kDa. By Sephadex G-100 chromatography, the factor eluted just ahead of bovine serum albumin (68 kDa). The activity of the suppressor factor could not be inhibited by anticryptococcal antibody, but it was inhibited by anti-I-J alloantiserum of the same genotype as the lymphocyte which produced the factor. Absorption with an encapsulated strain of Cryptococcus neoformans removed the suppressor factor from culture supernatants, while absorption with a nonencapsulated mutant or an unrelated yeast cell had not effect. On the basis of these observations, it was apparent that the suppressor factor was idiotypic in nature and that I-J and/or the I-J-interactive molecule played a role in the function of the suppressor factor. The requirement for antigenic stimulation for the production of suppressor factor in vitro distinguished it from the T-suppressor factor 3 described by others which regulates delayed-type hypersensitivity in cryptococcosis.
PMCID: PMC313355  PMID: 2656522
23.  Lymphocytes bearing Fc gamma receptors in rheumatoid arthritis. III. Immunoregulatory function associated with Facb rosette-forming cells. 
A subpopulation of mononuclear cells (PBMNC) that expresses Fc receptors with specificity for the C gamma 2 region of IgG may be detected by rosette formation with calf erythrocytes coated with the Facb fragment of rabbit IgG. These Facb-R+ cells are found in increased numbers in the peripheral blood of patients with rheumatoid arthritis (RA). Studies have been carried out to identify the functional properties of these cells in healthy and rheumatoid subjects. Facb-R+ cells were shown to lack both natural killer and antibody-dependent cytotoxic activity. Depletion of Facb-R+ cells from both healthy and rheumatoid PBMNC resulted in a marked suppression of pokeweed mitogen (PWM) stimulated IgG synthesis but had no effect on T cell proliferation induced by phytohaemagglutinin, concanavalin A, or PWM. The addition of Facb fragments to PBMNC cultures also caused inhibition of PWM-driven IgG production. In this assay rheumatoid PBMNC were significantly less sensitive to Facb-mediated suppression than healthy control cells. Our results suggest that Facb-R+ cells are involved in the antibody-mediated feedback regulation of immunoglobulin synthesis and that this mechanism is impaired in patients with RA.
PMCID: PMC1001559  PMID: 3155933
24.  Lymphocytes bearing Fc gamma receptors in rheumatoid arthritis. II. Phenotypic characterisation of mononuclear cells forming Facb rosettes in RA. 
We have previously reported an increased proportion of Facb-rosette forming cells in the peripheral blood of patients with rheumatoid arthritis in comparison with healthy controls. The present study investigates the surface phenotype of these cells by means of monoclonal antibodies and a variety of rosetting and lymphocyte fractionation techniques. Facb-R+ cells were found to lack surface markers characteristic of T and B lymphocytes. Studies with monoclonal reagents showed a positive reaction with OKIa1, OKM1, and another monocyte-specific antibody. Fac-R+ cells were recognised by anti-HLA-DR reagents but did not bind the monoclonal antibody 17.15 that recognises a determinant on HLA-DR antigens expressed by lymphocytes but not monocytes. These results show that Facb-R+ cells share certain surface characteristics with monocytes, though they are not phagocytic. These observations are consistent with an accessory role for Facb-R+ cells in the immune response.
PMCID: PMC1001558  PMID: 3155932
25.  Safer surgery for all. 
PMCID: PMC1247754  PMID: 3117322

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