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D Simmons

Publications and source records attributed to D Simmons.

At least 181 records · Page 10Linked to original sources
PubMed1989

A human macrophage-associated antigen (CD68) detected by six different monoclonal antibodies.

Antibodies grouped together by the Third Workshop on Leucocyte Differentiation Antigens on the basis of pan-macrophage reactivity on tissue sections were analysed in immunoprecipitation experiments. Antibodies Y2/131, EBM11, Ki-M6 and Ki-M7 all precipitated antigens of Mr 110,000 which were shown to be identical by preclearing experiments. In addition a recently produced antibody, KP1, which identifies macrophages in paraffin-embedded tissue, was shown to recognize the same antigen. The antibodies were tested on murine cells transfected with two clones, which had been isolated by screening a cDNA library with antibodies Y1/82A and EBM11. Cells transfected with the longer cDNA clone, coding for a molecule of Mr 110,000, reacted with antibodies Y2/131, EBM11, Y1/82A and Ki-M6, whilst the shorter clone, encoding a molecule of Mr 70,000 gave the same result except that it did not induce expression of the Ki-M6 epitope. KP1 antibody did not recognize any transfectants, possibly because of differences in glycosylation by the transfected cell line compared with human tissue. Five of the six antibodies appear to recognize different epitopes (the sixth, Ki-M7, not having been evaluated in this way). It was concluded that these six antibodies react with a macrophage-associated antigen for which the gene has been cloned. This group of antibodies has recently been designated CD68 by the Fourth Workshop on Human Leucocyte Differentiation Antigens.

Antibodies, Monoclonal↗
PubMed1989

Molecule detected in formalin fixed tissue by antibodies MT1, DF-T1, and L60 (Leu-22) corresponds to CD43 antigen.

Three monoclonal antibodies MT1, L60 (Leu-22), and DF-T1, were reported independently as recognising human T cells in routinely processed, paraffin wax embedded tissue. The present study was performed to compare these three reagents in terms of their immunocytochemical reactions and target molecule(s). On Western blotting of white cell extracts the three antibodies reacted with antigens of the same molecular weight (range 110-160 kilodaltons). Furthermore, their immunocytochemical reactivity with normal human cells, as analysed by two-colour flow cytometry, was essentially identical (labelling of monocytes, most T lymphocytes, and weak reactions with some B cells), and the antibodies gave closely similar reactions on 54 white cell derived neoplasms. To identify the target antigen for these three reagents, antibodies from the Third International Workshop on Leucocyte Antigens were reviewed and it was shown that the Western blotting and immunocytochemical reactions of MT1, L60 (Leu-22), and DF-T1 were identical with those of the reagents which defined the CD43 antigen (also known as leucosialin or sialophorin). Furthermore, all these antibodies reacted with cells transfected with a cDNA clone encoding CD43. It is concluded that antibodies MT1, L60 (Leu-22), and DF-T1 all recognise the heavily glycosylated myeloid/lymphoid associated CD43 antigen.

Antibodies, Monoclonal↗
PubMed1989

Intensive combination drug therapy of familial hypercholesterolemia with lovastatin, probucol, and colestipol hydrochloride.

Patients with familial hypercholesterolemia (FH) have had a life-long sustained elevation of low-density lipoprotein (LDL) cholesterol levels. Consequently, there is a need to maximally lower their elevated levels, and this usually requires lowering LDL levels more than 50%. Because no single hypolipidemic drug will consistently produce such degrees of lowering, combination drug therapy with two or even three agents is required to produce the desired degree of cholesterol lowering. A prospective trial was designed to determine if combination therapy using three hypolipidemic agents could effectively lower LDL levels in 17 severely affected FH subjects. Colestipol hydrochloride (10 g b.i.d.), probucol (500 mg b.i.d.), and lovastatin (20 or 40 mg b.i.d.) were given to each patient, in varying combinations, over a 25-month period. Lovastatin (40 mg/day) uniformly lowered LDL levels 36%. Probucol lowered LDL only 14% and in a variable manner. The combination of lovastatin and probucol lowered LDL no better than lovastatin alone. Lovastatin plus colestipol lowered LDL 52%; probucol added as a third agent produced no further lowering. Lovastatin (80 mg/day) plus colestipol lowered LDL 56%. Lovastatin increased high-density lipoprotein (HDL) cholesterol levels 6%, whereas probucol decreased HDL 29%. In all patients there was an effective lowering of LDL levels, ranging from 40% to 70%. Thus, lovastatin plus colestipol is an effective hypolipidemic regimen for producing marked decreases in LDL levels in FH subjects. The addition of probucol as a third hypolipidemic agent adds little to the therapeutic regimen as measured by lowering of LDL levels.

Cholesterol↗
PubMed1989

Glycaemic control affects cellular sodium metabolism.

Total and amiloride sensitive leucocyte sodium influx in Media containing 10 mmol/l Na was studied directly using a triple isotope method for measuring initial 22Na uptake rates in 25 non insulin dependent diabetic subjects. Glycaemic control was assessed by glycated haemoglobin and fasting blood glucose. Although no significant relationship between Na flux and either plasma insulin or blood glucose could be found, glycated haemoglobin was significantly correlated with both total and amiloride sensitive flux. Glycaemic control must be considered in future work on cellular sodium metabolism.

Amiloride↗
PubMed1988

Isolation of a cDNA encoding CD33, a differentiation antigen of myeloid progenitor cells.

A cDNA clone encoding the human myeloid Ag CD33 was isolated from a U937 cDNA library after three rounds of transient expression in COS cells and enrichment by panning. COS cells transfected with the isolated clone expressed a surface protein recognized by the anti-CD33 mAb MY9, L1B2, and L4F3, having mass similar to but slightly smaller than the mass of CD33 expressed on myeloid cells. CD33 transcripts were found constitutively expressed in several myeloid progenitor cell lines. The cDNA sequence predicts a 40-kDa polypeptide with the typical features of a glycosylated integral membrane protein. The extracellular part of CD33 contains two Ig-like domains which are highly related to the first two domains of the neural cell myelin-associated glycoprotein and the B cell Ag CD22.

Amino Acid Sequence↗
PubMed1988

The Fc gamma receptor of natural killer cells is a phospholipid-linked membrane protein.

Three types of receptor for the Fc (constant) region of human immunoglobulin G have been described; FcRI, a high-affinity (Ka approximately equal to 10(8) M-1) receptor expressed on monocytes; FcRII (CD32), a low-affinity (Ka approximately equal to 10(6) M-1) receptor expressed on B cells, granulocytes, macrophages and platelets; and FcRIII (CD16, FcRIo), a low-affinity receptor expressed on macrophages, neutrophils, eosinophils, natural killer cells and a subset of T cells believed to comprise the suppressor cells. Anti-CD16 antibodies block natural killer-cell mediated antibody dependent cellular cytotoxicity (ADCC). Binding of aggregated IgG to CD16 on natural killer cells leads to the expression of lymphocyte activation antigens, mediator release, morphological changes and lytic activity. We report here the isolation of a complementary DNA clone encoding CD16 determinants which gave rise to IgG binding of the expected affinity and subtype specificity in COS cells, and which proved to encode a phospholipid anchored protein. A single messenger RNA transcript was found in all positive RNA samples, and N-glycanase treatment showed the form found in COS cells was identical to the form present on peripheral blood mononuclear cells (PBMCs). We also show that CD16 is most closely related to the alpha-form of the murine IgG 2b/1 receptor and propose that extracellular contacts mediate the signal initiated by IgG binding.

Amino Acid Sequence↗
PubMed1988

ICAM, an adhesion ligand of LFA-1, is homologous to the neural cell adhesion molecule NCAM.

Antigen-specific cell contacts in the immune system are strengthened by antigen-nonspecific interactions, mediated in part by lymphocyte-function associated (LFA) antigens. The LFA-1 antigen is widely expressed on cells of haematopoietic origin and is a major receptor of T cells, B cells and granulocytes. LFA-1 mediates the leukocyte adhesion reactions underlying cytolytic conjugate formation, helper T-cell interactions, and antibody-dependent killing by natural killer cells and granulocytes. Recently, ICAM-1 (intercellular adhesion molecule-1) has been defined as a ligand for LFA-1. Monoclonal antibodies to ICAM-1 block T lymphocyte adhesion to fibroblasts and endothelial cells and disrupt the interaction between cytotoxic T cells and target cells. In addition, purified ICAM-1 reconstituted into artificial membranes binds LFA-1+ cells. ICAM-1 is found on leukocytes, fibroblasts, epithelial cells and endothelial cells and its expression is regulated by inflammatory cytokines. LFA-1 has been placed in the integrin family of cell surface receptors by virtue of the high sequence similarity between the LFA-1 and integrin beta chains. The adhesion ligands of the integrin family are glycoproteins bearing the Arg-Gly-Asp (RGD) sequence motif, for example, fibronectin, fibrinogen, vitronectin and von Willebrand factor. Here we show that a complementary DNA clone ICAM-1 contains no RGD motifs, but instead is homologous to the neural cell adhesion molecule NCAM.

Amino Acid Sequence↗
PubMed1988

Leucocyte sodium efflux and electrolyte content in insulin treated diabetes.

Leucocyte sodium efflux and sodium content were studied in 41 insulin treated diabetic patients and compared to 41 age, body mass index and blood pressure matched nondiabetic control subjects. Fasting leucocyte 22Na ouabain-sensitive efflux rate constants were lower in diabetic patients (median [range] 2.30 [1.04-3.73] versus 2.45 [1.57-3.95] h-1, p less than 0.4) suggesting a reduced sodium pump activity. The 22Na ouabain-insensitive efflux rate constant which reflects passive sodium efflux was raised in insulin treated diabetes (0.92 [0.42-1.73] versus 0.79 [0.28-1.49] h-1, p less than 0.01). Leucocyte sodium content was raised in the diabetic patients (47.7 [26.9-93.4] versus 26.5 [15.9-67.7] mmol/kg, p less than 0.0001). Abnormal cellular sodium handling could lead to hypertension or other complications in diabetes.

Adult↗
PubMed1988

Care and sterilization of endourologic instruments.

All endourologic instruments must be handled properly if they are to continue to function properly. Care must be taken in washing and sterilizing of this equipment, as not all endoscopic equipment can endure all methods, and people who are working with these instruments must be taught the proper care and sterilization methods of each. For example, fiberoptic telescopes and light cables must never be autoclaved; ethylene oxide is the method of choice. Disinfectant is an alternative. Loops, sheaths, high-frequency cables, resectoscopes, and working elements should be sterilized by ethylene oxide. Loops and high-frequency cables should not be soaked in a disinfectant, but other instruments may be soaked. All instruments should be dried before sterilization. Too much emphasis cannot be placed on the importance of proper storage of these very fragile fiberoptic instruments. With proper care and sterilization, these instruments will need fewer repairs and function properly for a longer time.

Disposable Equipment↗
PubMed1987

A malaria protein exported into a new compartment within the host erythrocyte.

A Plasmodium falciparum protein which is exported into a new compartment in the host erythrocyte has been located. This protein, exp-1, has a variable region recognized by a monoclonal antibody. Naturally occurring mutants of this region have been characterized. All mutants studied so far have the same A----G transition abolishing the target for the antibody. The exp-1 gene has a complex structure containing two introns. It is highly conserved in five independent, genetically defined parasite lines, suggesting that exp-1 has an important function. We discuss the possible role of exp-1 in P. falciparum infections.

Amino Acid Sequence↗
PubMed1986

Influence of amino acids encoded in the 3' open reading frame of the SV40 early region on transformation and antigenicity of large T antigen.

The mutant dlA2414 bears a frame-shift deletion of nucleotides 2936-2927 in the coding sequence for the simian virus 40 (SV40) large T antigen. Based on its nucleotide sequence, this mutant should produce a T antigen containing the first 627 authentic large T antigen amino acids followed by 97 amino acids encoded in the alternate open reading frame at the 3' end of the early region. This protein resembles the hypothetical T* protein that would be translated from an early SV40 mRNA if it were spliced to permit utilization of the open reading frame. We show that stable mouse cell lines can be generated that express the T antigen produced by dlA2414 and that this T antigen has an altered carboxy terminus. In addition, the expected tryptic peptides were missing from the large T antigen and replaced by more hydrophobic peptides. The T*-like protein produced by dlA2414 was apparently less stable than wild-type T antigen and did not stably complex with the cellular phosphoprotein p53. This protein retained the ability to immunize mice against a challenge of syngeneic SV40-tumor cells. The dlA2414 T antigen was expressed at the surface of cells as shown by in vitro lymphocyte-mediated cytotoxicity assay. The results presented here also showed that the expression of a T*-like protein at the cell surface is not likely to be essential for tumorigenesis of cells transformed by SV40.

Amino Acids↗
PubMed1986

Mapping of brain areas expressing RNA homologous to two different acetylcholine receptor alpha-subunit cDNAs.

We have used an in situ RNA X RNA hybridization technique to determine, in the central nervous systems of the mouse and rat, the distribution of RNA homologous to cDNA clones encoding the alpha subunit of a putative neural nicotinic acetylcholine receptor and the alpha subunit of the muscle nicotinic acetylcholine receptor. Hybridization of the neural alpha-subunit probe was strongest in the medial habenula but was also detected consistently in the compact part of the substantia nigra and ventral tegmental area, in the neocortex, and in certain parts of the thalamus and hypothalamus. The in situ hybridization technique makes it possible to compile a map of brain regions containing cell bodies expressing RNA coding for a specific receptor type and subsequently to apply the techniques of molecular biology to study these brain receptors.

Animals↗
PubMed1986

Blood pressure and salt intake in Malawi: an urban rural study.

A significant difference between the blood pressures of rural and urban Malawians was found in both sexes, was present at the age of 15 years, and was associated with obesity but not with smoking, alcohol consumption, occupation or housing. Pulse rate was significantly lower in the urban group. These differences were accompanied by low potassium and sodium intake although the sodium intake in the urban group was double that in the rural group. No direct relation between blood pressure and urinary electrolytes was found.

Anthropometry↗