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Biomedical subjects

H Sadeghi

Publications and source records attributed to H Sadeghi.

At least 55 records · Page 3Linked to original sources
PubMed1995

Selective induction of interleukin-1 receptor antagonist and interleukin-8 in human monocytes by normal polyspecific IgG (intravenous immunoglobulin).

We have investigated the effects of intravenous immunoglobulin (IVIg), a therapeutic preparation of normal human polyspecific IgG, on the synthesis and release of cytokines by peripheral blood monocytes. IVIg was found to selectively induce gene transcription and secretion of interleukin-1 receptor antagonist (IL-1ra) and IL-8 in cultures of normal human monocytes. The addition of IVIg to cultures of purified monocytes induced a dose-dependent secretion of IL-1ra and IL-8 without stimulating the production of IL-1 alpha, IL-1 beta, tumor necrosis factor-alpha or IL-6. The effects of IVIg required both the Fc and F(ab')2 portions of IgG. IVIg-induced production of IL-8 by monocytes was enhanced by lipopolysaccharide (LPS), although LPS inhibited the secretion of IL-1ra, suggesting that IVIg and LPS stimulate distinct intracellular pathways in monocytes. Induction of IL-1ra and IL-8 by IVIg was enhanced in the presence of autologous T lymphocytes. Our observations document the selectivity of the effects of IVIg on the synthesis of cytokines and cytokine antagonists by human monocytes. Induction of IL-1ra and IL-8 by IVIg may contribute to the anti-inflammatory effects of immunoglobulin therapy in patients with autoimmune and systemic inflammatory disorders.

Cell Communication↗
PubMed1995

Cardiac perforation after surgical repair of pectus excavatum.

Five days after surgical repair of pectus excavatum, this 7-year-old boy had a right-sided Kirschner wire protruding beneath the skin. The wire was repositioned blindly. Severe congestive heart failure developed. Surgical exploration showed a pierced right atrium, a torn septal leaflet of the tricuspid valve and noncoronary aortic cusp, and a large traumatic ventricular septal defect. The outcome and the indications and possible complications of surgery are discussed.

Bone Wires↗
PubMed1995

Incidence of deep and superficial sternal infection after open heart surgery. A ten years retrospective study from 1981 to 1991.

Between January 1981 and December 1991, 4137 adult patients underwent various cardiac procedures via a median sternotomy under cardiopulmonary bypass. The overall infection rate was 1.33%, including superficial wound infections (SWI) (1.18%) and deep sternal infection (DSI) (0.145%). Pericardial and retrosternal suction drains with a vent allowed a better drainage of blood and serosities and probably contributed to our low DSI rate. Eleven factors predisposing to infection were evaluated by Fisher's exact test. Only the operative urgency (P = 0.006), reexploration for bleeding (P = 0.00001) and preoperative renal failure (P = 0.0005) were statistically significant. Twenty of our infected patients had no risk factors for infection. When the risk factors described in the literature were applied to our infected patients, only one had no risk factor.

Adolescent↗
PubMed1995

Surgery in native valve endocarditis: indications, results and risk factors.

Seventy-nine patients (mean age 49 years) underwent valve replacement or repair for active (58.2%) or healed (41.8%) native valve endocarditis between 1976 and 1992. The most common indication for surgery was congestive heart failure (73.4%), followed by multiple systemic emboli (21.5%). Emergency operation was necessary in 27.8% of the cases. Operative mortality was 3.8% (3 patients) and late mortality 15.1% (12 patients). Streptococci were the most common infecting agents (41.8%), followed by Staphylococcus aureus (11.4%). No organisms were isolated in 27 cases (34.2%). Follow-up spanned 379.8 patient-years with a maximum of 15.8 years. Fifteen late valve-related events (periprosthetic leak, recurrent endocarditis, thrombo-embolic events and hemolysis) and 20 other late complications (anticoagulant-related hemorrhage, arrhythmias or congestive heart failure) occurred in 22 patients. The linearized rate for all late complications is 5.8% per patient-year. The influence of eight preoperative variables on overall mortality and late valve-related complications was assessed: age, valve(s) affected, active or healed infection, bacteriology, annular abscess, emergency or elective surgery, preoperative renal function and NYHA class. Only Staphylococcus aureus (P = 0.0012) was a significant predictor of late valve-related complications. Furthermore, no difference in survival or in valve-related complications was found between the active and healed infections.

Actuarial Analysis↗
PubMed1995

Augmentation of the effectiveness of porcine GH with swine antibodies induced by a synthetic GH peptide.

An effort was made to evaluate the potential usefulness of a peptide vaccine in improving the growth performance of farm animals. It was previously reported that a murine PS-7.6 monoclonal antibody (mAb) which was specific to porcine GH (pGH) enhanced the growth-promoting activity of pGH in an experimental hypophysectomized rat model. Additional data from a epitope mapping study suggested that PS-7.6 mAb recognized a pGH fragment corresponding to an amino acid sequence 54-95. In this report, therefore, a peptide pGH(54-95) was synthesized in an attempt to induce PS-7.6-like antibodies in swine. It was demonstrated that the peptide pGH(54-95) competed with PS-7.6 mAb for the binding to radioactive pGH in a competition radioimmunoassay and also caused pigs to elicit polyclonal antibodies immunoreactive to pGH protein. The association and dissociation rate constants of the swine antibody to pGH were 1.9 x 10(2) M-1 s-1 and 3.2 x 10(-4)s-1 respectively, thus producing an overall binding affinity of Kd = 1.6 x 10(-6) M. The swine antibody partially competed with murine PS-7.6 mAb for the binding to pGH, suggesting that the pGH-recognizing sites for both antibodies might be closely related. The biological effect of the swine antibody was examined in hypophysectomized rats and shown to significantly augment pGH activity in promoting the growth of these GH-deficient animals. The present findings suggest that a synthetic peptide may be developed as a potential growth vaccine for swine to generate antibodies capable of enhancing the effectiveness of endogenous pGH.

Animals↗
PubMed1994

[Infectious complications in cardiac transplantation: Lausanne experience].

Infectious complications, a major cause of morbidity and mortality after heart transplantation, were reviewed in 49 heart transplant patients at Lausanne. The follow-up lasted 32 months on average. 43 patients (88%) presented 108 infections (2.20 episodes of infection/patient). 38 severe infections (0.78 episodes/patient) were diagnosed in 27 patients (55%). 2 of the 9 deaths which occurred were due to infection. The viruses, principally of the herpes group, were responsible for 37% of all the infections, and bacteria for 28%. About a third of the viral and bacterial infections were severe. The other documented infections were caused by fungi (13%), which were most often responsible for superficial infections, and rarely by protozoa (5%). Finally, in 17% of infectious episodes, the pathogen could not be identified. Cytomegalovirus was the pathogen the most frequently responsible in severe infections. The highest incidence of infections occurred during the first 2-3 months after transplantation and was reduced considerably after the 6th month. The distribution of different pathogens was related to specific periods after the transplant. Our results confirm that infection is a major complication of heart transplantation. Clinical and prophylactic aspects of some infections are reviewed.

Cytomegalovirus Infections↗
PubMed1994

Coronary angioplasty versus left internal mammary artery grafting for isolated proximal left anterior descending artery stenosis.

Coronary artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA) are more effective than medical treatment for the management of ischaemic heart disease. However, patients with single-vessel involvement have been excluded from prospective comparisons of the two methods. We have carried out such a comparison in patients with isolated proximal left anterior descending artery stenosis, conserved left ventricular function, and documented ischaemia. Eligible patients presenting to a single centre were randomly assigned PTCA (68 patients) or left internal mammary grafting (66). The procedures were technically feasible in all cases. The incidence of in-hospital complications was 2% (perioperative myocardial infarction) for CABG and 3% (emergency CABG for acute closure) for PTCA. Clinical and functional status improved similarly in both groups. However, patients in the PTCA group took more antianginal drugs. At median follow-up of 2.5 years, 86% of CABG-treated and 43% of PTCA-treated patients were free from adverse events (p < 0.01; relative risk 2.0 [95% CI 1.7-2.3]). The adverse events that explain this difference were restenosis (32%) requiring subsequent surgical (16%) or percutaneous (15%) revascularisation (1% had medical therapy). Rates of cardiac death and myocardial infarction did not differ between the groups. Both CABG and PTCA improve the clinical status of symptomatic patients with single-vessel coronary artery disease. If patient and physician accept the risk of restenosis and reintervention associated with PTCA, this procedure remains a suitable option and a simpler initial alternative to CABG.

Angioplasty, Balloon, Coronary↗
PubMed1994

Generation of heterohybridomas capable of releasing swine monoclonal antibody specific to porcine growth hormone.

An effort was made to generate stable swine hybridomas capable of releasing monoclonal antibodies (MAb) with antigenic specificity. Crossbred pigs were immunized with recombinant porcine growth hormone (r-pGH) and the splenic cells were harvested from these animals. B lymphocytes enriched by gradient centrifugation and nylon wool adherence were briefly stimulated in vitro with r-pGH prior to hybridization with murine SP2/0 myeloma cells. The fused hybrids were screened for their ability to produce anti-pGH antibody and the positive ones were subcloned by a limiting dilution procedure. The stable cell lines were maintained by serial passages in cultures for further analysis. One such hybridoma, designated PM20/20, was found to secrete swine IgM. It recognized not only the immunizing r-pGH but also the native pGH extracted from the swine pituitary glands, as demonstrated by Western analysis. It also recognized two smaller fragments with m.w. of 10 kD and 5 kD of r-pGH following trypsin digestion. In addition to pGH, PM20/20 immunoreacted with several other GH species including bovine, chicken, and human origins, but not with ovine prolactin nor rat GH binding protein. The binding association rate constant and dissociation rate constant of PM20/20 to pGH were 5.3 x 10(4) M-1 s-1 and 1.0 x 10(-4) s-1, respectively, thus producing a dissociation constant of 1.9 x 10(-9) M. Therefore, stable swine-mouse heterohybridoma lines have been established and shown to continuously release swine mAb in cultures. These mAb may serve as useful alternatives to murine mAb in certain areas of research.

Animals↗
PubMed1993

[Long-term treatment of patients with dissection of the thoracic aorta].

Thoracic aortic dissection is an extremely serious vascular accident which must be treated immediately. While ascending aortic dissection requires surgery as soon as possible, descending aortic dissection is only treated surgically when complications such as aortic ectasia, hemorrhage or ischemia occur. Late complications most often lead either to the patient's death or to reoperation. Late death occurs in 4-6% patients/year and about 3% patients/year undergo late reoperation. In our own experience these figures amount to 2 and 0.8% respectively.

Aortic Dissection↗
PubMed1993

Inhibitory effect of growth-enhancing antibody on the interaction between growth hormone and growth hormone binding protein.

A monoclonal antibody (mAb), designated PS-7.6, was generated in mice by immunizing these animals with recombinant porcine growth hormone (pGH). This antibody has been previously shown to enhance the growth-promoting activity of pGH in an experimental rat model. An effort was made in this report to further characterize the immunologic properties of this antibody and its effect on the interaction between pGH and GH binding protein (GHBP). This antibody was classified as IgG1 isotype and found to be highly specific to pGH in a competition radioimmunoassay (RIA). It did not recognize several other GHs including those of bovine, chicken and human origins, nor several growth related factors including prolactin, insulin, somatostatin and growth hormone releasing factor. In Western analysis, PS-7.6 mAb identified not only the 22.5 kDa recombinant pGH, but also the native pGH in swine pituitary gland. An additional 45 kDa protein was also detected in the gland by the antibody, presumably a dimer form of pGH. The association and dissociation rate constants of the antibody as determined by biospecific interaction analysis (BIA) were 2.43 x 10(4) M-1 s-1 and 1.29 x 10(-3) s-1, respectively and its affinity (Kd) was 4.85 x 10(-8) M. Furthermore, PS-7.6 mAb prevented pGH from interacting with GHBP in RIA and BIA, indicating that the antibody epitope closely associated with the pGH binding region for GHBP. Therefore, present findings suggest that a possible mechanism of action of PS-7.6 mAb in enhancing animal growth is to prevent pGH from being bound to GHBP in circulation, thus making more pGH available to tissue receptors.

Animals↗
PubMed1993

Ultrastructural colocalization of growth hormone binding protein and pituitary hormones in adenohypophyseal cells of the rat.

GH receptor immunoreactivity is widely distributed within the rat pituitary gland, although apart from somatotrophs the cell types with GH receptor immunoreactivity have yet to be identified. It is also unknown whether this immunoreactivity reflects the presence of GH binding proteins (GHBPs) or authentic receptors. The possible colocalization of GHBPs and pituitary hormones in somatotrophs, lactotrophs, gonadotrophs, thyrotrophs, and corticotrophs was therefore examined using immunogold electron microscopy. Pituitary sections were indirectly immunostained with antibodies for GH, PRL, LH, FSH, TSH, or ACTH using gold-labeled immunoglobulin G. The same grids were also immunostained with a polyclonal antibody raised against rat GHBP using protein A conjugated to gold particles of a different size. Some sections were gold-labeled using a monoclonal antibody (MAb 4.3) raised against the unique hydrophobic tail of the GHBP, using gold-labeled immunoglobulin G. The cellular and ultrastructural distribution of immunoreactivity within the pituitary gland was similar after labeling with either GHBP antiserum. In all immunoreactive cells the labeling was most intense in secretory granules. Specific staining was not, however, demonstrated in the nucleus, in contrast with earlier findings using MAb 263. Moreover, while staining with MAb 263 appeared to be ubiquitous, some pituitary cells were not labeled by the polyclonal GHBP antiserum or by MAb 4.3. GHBP immunoreactivity was, however, colocalized with hormones in all pituitary cell-types, although in some cells GHBP immunoreactivity was not present in all secretory granules. These results clearly demonstrate the presence of GHBPs in adenohypophyseal cells, in which they appear to be stored or secreted with GH, PRL, LH, FSH, TSH, and ACTH. The function of GHBPs in the pituitary gland is, however, uncertain.

Adrenocorticotropic Hormone↗
PubMed1993

Interaction of monoclonal antibodies with growth hormone-binding protein and its complex with growth hormone.

The properties of four independent lines of monoclonal antibodies (MAbs) specific to rat GH-binding protein (GHBP) were examined. Three MAbs, designated GHR-12, GHR-13 and GHR-16, were raised against the entire GHBP molecule. The fourth MAb, designated as GHBP4.3, was raised against the 17 amino acid residues at the C-terminal end of rat GHBP. The interaction of these antibodies with GHBP and their effect on GH binding to GHBP were analysed by conventional competition binding assays and surface plasmon resonance, i.e. with a Biospecific Interaction Analysis (BIAcore) instrument. The binding affinity of these MAbs to GHBP ranged from 29 nmol/l to 30.9 pmol/l. The pair-wise antibody binding to GHBP on BIAcore suggested that GHR-13 and GHR-16 recognized different antigenic determinants while part of the GHR-12 epitope might be shared with the other antibodies. The antibodies inhibited the interaction of GH with GHBP in the competition binding assay. However, in sequential binding on the BIAcore instrument, they were able to bind GHBP after its interaction with GH, indicating that the inhibition observed in the competition binding assay resulted from steric hindrance rather than direct interference with the GH-binding site of GHBP. The present findings, therefore, suggest that these antibodies are useful for investigating GHBP and its interaction with GH.

Animals↗
PubMed1992

[Heart valve substitution: the effect of preoperative findings on long-term outcome].

BACKGROUND: In a retrospective analysis of 653 consecutive patients who underwent heart valve replacement by one single type of mechanical prosthesis (St. Jude Medical) at three Swiss university medical centers (Basel, Bern, Lausanne), the outcome was judged on the basis of preoperative variables. These variables should facilitate the timing of heart valve replacement. METHODS: Preoperative evaluation includes NYHA classification of symptoms, chest X-ray, ECG, and LVEF on angiography. Postoperative outcome was assessed clinically at yearly intervals by NYHA classification, documentation of complications and mortality. RESULTS: Five-year-survival rates were 96 and 88%, and complication-free rates were 82 and 76% respectively in patients after isolated aortic and mitral valve replacement. An unsatisfactory outcome with death or persistent severe symptoms was more frequent when preoperative symptoms at rest and atrial fibrillation were present. CONCLUSION: Heart valve replacement should not be postponed until severe symptoms and functional impairment occur. Clinical criteria are at least as important for the timing of operation as the findings of more complex investigations.

Adolescent↗