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Biomedical subjects

H Sadeghi

Publications and source records attributed to H Sadeghi.

At least 73 records · Page 4Linked to original sources

N-Acetyl-beta-D-glucosaminyl-binding properties of the envelope glycoprotein of human immunodeficiency virus type 1.

The effect of carbohydrate structures on the adsorption of HIV-1 or of recombinant envelope glycoprotein gp 160 (rgp 160) to cells of the CEM line was investigated with an indirect immunofluorescence assay using gp 120-specific mouse monoclonal antibodies (mAbs) directed to envelope gp 120. The beta-D-galactosyl, alpha-D-mannosyl, beta-D-glucosyl, N-acetyl-beta-D-glucosaminyl, sialosyl, and L-fucosyl derivatives tested had no effect on this binding. However, preincubation of HIV-1 (or rgp 160) with the neoglycoprotein, beta-D-GlcNAc47-BSA, specifically inhibited the labeling, by some of the mAb used, of HIV-1 (or rgp 160) bound at the cell membrane. This inhibition occurred only with mAbs that were specific for the immunodominant "neutralizing" third variable region (V3) of gp 120. Competition for the binding to rgp 160 between beta-D-GlcNAc47-BSA and mAb was further demonstrated by use of affinity matrices substituted with one of the relevant mAb (110-4), or with beta-D-GlcNAc47-BSA. Besides beta-D-GlcNAc47-BSA-Sepharose, rgp 160 also bound with low affinity, but high specificity, to two other N-acetyl-beta-D-glucosaminyl affinity matrices, beta-D-GlcNAc-divinylsulfone-agarose and asialoagalactothyroglobulin-agarose. Conversely, beta-D-[125I]GlcNAc47-BSA bound specifically to gp 160-Sepharose. These results indicated that rgp 160 behaves as a N-acetyl-beta-D-glucosaminyl-binding protein for GlcNAc residues presented at high density on a carrier, the carbohydrate-binding site of which is close to, or located on the V3 region of gp 120.

Acetylglucosamine↗

[Late neurological complications of heart transplantation].

To assess anomalies in these subjects, an ambulatory neurological examination was performed in 12 heart transplant patients and in 1 heart-lung transplant patient. The patients were examined between the 3rd and 51st month following the transplantation. Two had symptoms due to a previous neurological disease. Early postoperative complications were found in 6 patients (seizures in 3 cases, cerebral infarcts in 1 case, anoxia in 1 case and right ulnar nerve damage at the elbow in 1 case). Late postoperative complications included postural tremor (9 cases) or mild polyneuropathy (2 cases). Neurological examination was completely normal in 2 patients. The findings show that the most common late neurological abnormality found in heart transplant patients is postural tremor.

Adult↗

Dissolution of peripheral arterial thrombi by ultrasound.

BACKGROUND: We have previously shown that continuous-wave ultrasound can rapidly dissolve human thrombi in vitro, with 99% of all residual particles measuring less than 10 microns in diameter. To assess the effects of pulsed-wave ultrasound energy on whole blood clots, 1) in vitro studies were preformed to assess precisely the rates of clot disruption and to quantify particulate size, and 2) in vivo studies were performed to assess the efficacy and safety of catheter-delivered ultrasound for intra-arterial thrombus dissolution. METHODS AND RESULTS: In vitro, we studied 50 samples of human whole blood clots and using an 89-cm-long wire probe, applied pulse-wave energies from 8 to 23 W. The corresponding peak-to-peak tip displacement range was 63.5 - 102 microns. We studied arterial thrombosis in vivo in 21 canine superficial femoral arteries. To produce an acute thrombosis, 200 units of thrombin followed by 2 ml of 72-hour-old autologous clot were injected into a 5-7-cm segment of femoral artery and left to coagulate for 2 hours. Ultrasound energy was intermittently applied at a frequency of 20 kHz with a prototype ultrasound wire ensheathed in a catheter and directed to clots by fluoroscopy. In nine cases, angioscopic guidance was used to put the probe into direct contact with the intra-arterial thromboses. In vitro clot dissolution times were inversely related to the ultrasound power output (r = 0.95). All in vivo canine thromboses were disrupted in 4 minutes or less. All successful recanalizations were confirmed by angiography and in nine cases by angioscopy as well. Angioscopy demonstrated that probe activation caused rapid clot disruption. Histological studies of the vessels showed no evidence of thermal or cavitation injury, occlusive distal embolization, or perforation. CONCLUSIONS: Our findings in this experimental canine model suggest that ultrasound clot dissolution has the potential to be an effective and safe alternative to current treatment modalities for peripheral arterial thrombosis.

Animals↗

Complications after single versus dual chamber pacemaker implantation.

To compare the complication rate in patients having a dual chamber versus a single chamber pacing system, 337 consecutive procedures performed during a 3-year period were analyzed prospectively. Two hundred fifty-eight patients (77%) received a VVI pacemaker and 75 (23%) a DDD unit. Thirteen VVI (5%) and 4 DDD (5.3%) needed reintervention. Lead displacement with reoperation was required for three ventricular leads (1%) and one atrial lead (1.3%). Infection occurred in two VVI units (0.77%) and one DDD (1.33%) unit. Muscular stimulation was noticed among three DDD (4%) and nine VVI systems (3.5%). Urgent reprogramming was needed for 23 VVI (9%) and six DDD units (8%). There was no increase in complications with dual chamber pacing compared to single chamber systems.

Aged↗

Identification of the origin of the growth hormone-binding protein in rat serum.

GH specifically interacts with a soluble binding protein in serum. The GH-binding protein (GHBP) has been shown to contain the extracellular portion of the cell surface GH receptor (GHR). In rats and mice there is a unique mRNA that encodes the GHBP. This mRNA contains an alternatively spliced exon that replaces the transmembrane and intracellular domains of the receptor with a short hydrophilic carboxy-terminus of 17 and 25 amino acids, respectively, in rats and mice. In humans and other species no mRNAs encoding the GHBP have been identified, suggesting that the GHBP is in these cases a proteolytically processed GHR. In this study a monoclonal antibody (GHBP 4.3) was raised to the rat GHBP using as immunogen a synthetic peptide containing the unique C-terminal 17 amino acids that are not found in the rat GHR. As predicted, this antibody is specific to rat GHBP and does not cross-react with rat GHR. In combination with polyclonal and monoclonal antibodies that recognize both GHBP and GHR, this antibody was used to show that all, or most, of the GHBP in rat serum is indeed derived from the alternatively spliced GHBP mRNA and not from proteolytic processing of the GHR. In addition, endogenous rat serum GHBP was found to exist in two forms, with apparent mol wt of 52 and 44 kDa, arising from a single protein core of 32 kDa by extensive glycosylation. The concentrations of GHBP in male and female rat plasma were also estimated to be 300 and 575 ng/ml, respectively (measured in nonglycosylated GHBP equivalents).

Amino Acid Sequence↗

[Retrospective study of permanent cardiac stimulation in patients over 80 years of age].

Out of 833 pacemakers implanted between 1979 and 1983, 228 were in patients aged over 80 years (137 aged 80-84, 79 85-89, and 12 90-93). Indication for cardiac stimulation was high-grade atrioventricular (av) block in 47%, sick sinus syndrome in 38%, low ventricular response in atrial fibrillation in 13% and hypersensitivity of the carotid sinus in 1%. An average follow-up period of 29.5 months (18-78 months), focusing special interest on quality of life, revealed that of the 199 patients (87%) who were independent at the time of implantation, 29 (15%) became dependent on social services during the follow-up and during the same period 49 (21%) were rehospitalized (88 hospitalizations) for reasons other than pacemaker problems. During the first year after implantation the mortality in the "paced" population was higher than in the general population of the same age groups; thereafter the survival curves run almost parallel. Mortality does not differ between persons paced for av block of for sinus node disease. We conclude that cardiac stimulation in patients aged over 80 years allows them to preserve their lifestyle and independence when compared to the general population, with the same rate of survival.

Aged↗

Intravascular stenting for stenosis of aortocoronary venous bypass grafts.

To test the ability of endoluminal stents to prevent saphenous vein graft restenosis after balloon angioplasty, 13 patients with angina and previous coronary bypass surgery underwent implantation of one or more stents into 14 stenosed grafts. Implantation was technically successful in all cases and there were no major in-hospital complications. During a median follow-up interval of 7 months (range 2 to 26), 10 patients (77%) underwent follow-up angiography. Seven patients remained asymptomatic or in improved condition without further intervention; three patients had further angioplasty with stent implantation for a new stenosis in the same graft. Two patients (20%) developed within-stent restenosis. There was one death from progressive congestive heart failure 7 months after implantation. No patient had a myocardial infarction or needed surgical revascularization during the follow-up period. In selected cases, stent implantation appears to be a promising new technique that may decrease the incidence of restenosis after balloon angioplasty in venous bypass grafts. The rate of complications is low. Further experience and longer follow-up will be needed before definite recommendations can be made about its use.

Aged↗

Re-expression of 117 antigen, a cell surface glycoprotein of aggregating cells, during terminal differentiation of Dictyostelium discoideum prespore cells.

117 antigen is a glycoprotein expressed on the surface of D. discoideum cells at aggregation. It then disappears and is later re-expressed on the surface of a subpopulation of cells at culmination, the terminal differentiation stage (Sadeghi et al. 1987). A cDNA clone was used to show that the appearance of cell surface 117 antigen accurately reflects the expression of the 117 gene as measured by mRNA levels. It was also shown that during multicellular development there is a reciprocal relationship between the levels of 117 mRNA and the mRNA which codes for prespore surface glycoprotein, PsA. Dual parameter flow cytometry was used to demonstrate that the 117 antigen is found on the surface of maturing prespore cells after the PsA glycoprotein disappears, but that it is not found on mature spores. Using three monoclonal antibodies which identify respectively 117 antigen, PsA, and MUD3 antigen (a spore coat glycoprotein--probably Sp96), two new stages of final spore maturation were defined. These results indicate that there is a recapitulation of at least one aggregative cell surface glycoprotein in the prespore subpopulation of cells as they rise up the stalk during final spore development. This raises the possibility that culmination, which involves complex three dimensional morphogenetic movements not unlike those observed during animal embryogenesis, involves components of the two-dimensional pattern seen during aggregation.

Antigens, Differentiation↗

Biosynthesis of 117 antigen: a cell cohesion molecule in Dictyostelium discoideum.

117 antigen is involved in the process of intercellular cohesion in Dictyostelium discoideum [Brodie et al., 1983]. The antigen, a 69- and 72-kDa doublet, was found to arise from a 60- and 62-kDa precursor. The mature antigen contains N-linked oligosaccharides that are sulfated and fucosylated [Sadeghi et al., 1987]. These oligosaccharide chains are resistant to endoglycosidase H digestion. 117 antigen also contains a post-translationally added carbohydrate-containing modification(s). Unlike the N-linked oligosaccharide, this carbohydrate moiety is sensitive to periodate oxidation. 117 antigen is developmentally regulated, and the changes in rate of 117 antigen synthesis reflect changes in the cellular levels of its mRNA. 117 mRNA accumulates in starving cells and reaches its maximum when cells become aggregation competent. The mRNA levels then decline, and by the time the slug structure is formed, no 117 mRNA is present. 117 mRNA reaccumulates for a brief period during early culmination and then returns to an undetectable level.

Antigens, Fungal↗

Evidence that a glycolipid tail anchors antigen 117 to the plasma membrane of Dictyostelium discoideum cells.

We describe the biochemical features of the putative cell cohesion molecule antigen 117, indicating that it is anchored to the plasma membrane by a glycolipid tail. Antigen 117 can be radiolabeled with [3H]myristate, [3H]palmitate, and [14C]ethanolamine. The fatty acid label is removed by periodate oxidation and nitrous acid deamination, indicating that the fatty acid is attached to the protein by a structure containing carbohydrate and an unsubstituted glucosamine. As cells develop aggregation competence, the antigen is released from the cell surface in a soluble form that can still be radiolabeled with [14C]ethanolamine but not with [3H]myristate or [3H]palmitate. The molecular weight of the released antigen is similar to that found in the plasma membrane, but it preferentially partitions in Triton X-114 as a hydrophilic, as opposed to a hydrophobic, protein. Plasma membranes contain the enzyme activity responsible for the release of the antigen in a soluble form.

Antigens, Surface↗

Prevention of coronary restenosis by stenting.

Balloon angioplasty fails to provide acceptable long-term results for a significant proportion of patients. An intravascular mechanical support, developed with the aim of preventing restenosis and acute closure of diseased arteries after transluminal angioplasty, was implanted in 44 patients (39 male and five female), aged from 35 to 70 years (mean 56 years) with documented restenosis of native coronary artery (41 stents) and bypass grafts (12 stents). In the group of bypass graft patients there was no local restenosis and no major complication. In patients in whom stents were placed in native coronary arteries, the complication rate was higher (two patients died after coronary bypass surgery). One patient died suddenly at home. Except for one patient, in whom a new lesion developed proximally with extension into the stent, no case of restenosis could be observed. Despite the still relatively high complication rate, we feel that stenting may present a rational approach to the unresolved problem of restenosis after coronary angioplasty.

Adult↗

Inhibition of N-linked glycosylation in Dictyostelium discoideum: effects of aggregate formation.

The aggregation program of Dictyostelium discoideum is extremely sensitive to the effects of tunicamycin when the drug is added to cells during the first few hours of starvation. Inhibition of development is observed with concentrations as low as 0.5 micrograms/ml, which cause only a 25%-30% inhibition of general N-linked glycosylation. However, 0.5 micrograms/ml tunicamycin can result in the total inhibition of N-linked glycosylation of specific, developmentally regulated, proteins, as exemplified by the glycoprotein 117 antigen. If added after the first hours of starvation, tunicamycin cannot inhibit aggregation even when present at 10 micrograms/ml, which maximally inhibits N-linked glycosylation. cAMP pulses can override the inhibitory effects of tunicamycin on cell aggregation. The data support the hypothesis that there is an early developmental pathway that is dependent on the N-linked glycosylation of one, or a small set of developmentally regulated proteins and that this pathway may involve the biogenesis of the chemotactic signalling system. In addition, the data raise questions as to the role of N-linked oligosaccharides in cell cohesion.

Cell Aggregation↗

Characterization of antigen 117. A developmentally regulated cell surface glycoprotein of Dictyostelium discoideum.

Antigen 117 is involved in the process of intercellular cohesion in Dictyostelium discoideum (Brodie, C., Klein, C., and Swierkosz, J. Cell 32, 1115-1123 (1983]. The antigen was shown to arise from a 62,000-64,000-dalton precursor. The mature antigen consists of two forms of molecular weights, 69,000 and 72,000. These forms are glycosylated, phosphorylated, acylated, and sulfated. Developmental changes in the cellular and cell surface levels of the antigen reflect changes in its rate of synthesis. All aggregating cells express antigen 117 on their surfaces. Antigen 117 then disappears from the surface of all cells when tip formation occurs. The antigen is re-expressed briefly again on cells undergoing culmination.

Antibodies, Monoclonal↗

[Dysfunctions of heart valve prostheses and their surgical treatment].

Today the dysfunctions and complications relating to prosthetic cardiac valves are less frequent than 15-20 years ago. The materials used to manufacture mechanical cardiac valves, e.g. carbon pyrolyte, are much more resistant than Teflon or Derlin, and wear is therefore an exceptional event. In regard to bioprostheses, research is now aimed at preventing calcifications, tears and deterioration. Complications such as thrombosis and thromboembolic accidents are seen with all prosthetic cardiac valves and affect mechanical valves rather than bioprostheses. Hemorrhage, a complication of anticoagulant therapy, can be seen in any patient with a prosthetic cardiac valve undergoing such treatment. This complication is far less frequent in patients with a bioprosthesis since most of these (75%) are not on long-term anticoagulation. Paravalvular leakage is another rare complication related to valvular surgery and is often associated with prosthetic valve endocarditis. Prosthetic cardiac valve endocarditis is a very severe complication with a high mortality rate, and is more lethal when endocarditis occurs soon after surgery (up to 2 months). Elimination of infectious foci before surgery, observation of strict rules of asepsis, a high level of surgical technique, and prescribing of prophylactic antibiotic therapy during surgery, or later if necessary, will reduce the risk of prosthetic valve endocarditis. Where reoperation is decided for the above complications it is almost always necessary to replace the failing prosthetic valve.

Endocarditis↗

[Multiple peripheral emboli resulting from thrombosis of a St. Jude aortic valve prosthesis].

Although thrombosis of St. Jude valve prosthesis is rare, we report a case of multiple thromboembolism in a patient who had stopped anticoagulant therapy. The consequences were very severe since two abdominal operations (colonic resection) were necessary. Since the patient was not compliant with anticoagulant therapy, aortic valve replacement was performed and a biologic valve implanted. The postoperative phase was long but the patient left the hospital after two months' treatment. This case again demonstrates the importance of anticoagulant therapy in patients with a prosthetic heart valve. Addition of dipyridamole diminished the risk of thromboembolic accident and should be added to the anticoagulant regimen.

Anticoagulants↗