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Biomedical subjects

M Chelli

Publications and source records attributed to M Chelli.

At least 19 recordsLinked to original sources

Prevalence of inherited prothrombotic abnormalities and central venous catheter-related thrombosis in haematopoietic stem cell transplants recipients.

In this prospective study, we assessed the incidence of central venous catheter (CVC)-related thrombosis in haematopoietic stem cell transplant (HSCT) recipients. We determined the contribution of inherited prothrombotic abnormalities in blood coagulation to CVC-related thrombosis in these patients. The study was conducted between May 2002 and September 2004. CVCs were externalized, nontunneled, polyurethane double lumen catheters. Before catheter insertion, laboratory prothrombotic markers included factor V Leiden, the prothrombin gene Gly20210A mutation, plasma antithrombin levels, and protein C and S activity. All patients were systematically examined by ultrasonography just before, or <24 h after, catheter removal, and in case of clinical signs of thrombosis. A total of 171 patients were included during the 28-month study period. Five (2.9%) and three (1.7%) patients had evidence of protein C and protein S deficiency, respectively. Only one patient had an antithrombin deficiency (0.6%). In total, 10 patients (5.8%) were heterozygous for the factor V Leiden mutation, and one patient had heterozygous prothrombin G20210A mutation (0.6%). We observed a CVC-related thrombosis in 13 patients (7.6%). Thrombosis was diagnosed in four out of 20 patients (20%) with a inherited prothrombotic abnormality compared to nine of 151 patients (6%) who did not have a thrombophilic marker (relative risk 3.3 CI 95% 1.1-9.9). Our results suggest that inherited prothrombotic abnormalities contribute substantially to CVC-related thrombosis in HSCT recipients. In view of physicians' reluctance to prescribe prophylactic anticoagulant treatment in these patients, a priori determination of inherited prothrombotic abnormalities may form a basis to guide these treatment decisions.

Blood Coagulation Factors↗

Determinants of the trans-dominant negative effect of truncated forms of the CCR5 chemokine receptor.

The human immunodeficiency virus, type 1 (HIV-1) entry process is triggered by interaction between the viral envelope and a seven membrane-spanning domain receptor at the cell surface, usually the CCR5 chemokine receptor. Different naturally occurring mutations in the CCR5 gene abolish receptor function, the most frequent being a 32-nucleotide deletion resulting in a truncated protein (Delta32) lacking the last three transmembrane domains (TM5-7). This mutant is retained in the endoplasmic reticulum and exerts a trans-dominant negative (TDN) effect on the wild type, preventing its exit from this compartment. This TDN effect is often considered as evidence for the oligomerization of CCR5 during transport to the cell surface. Here we use a genetic approach to define the structural determinants of the TDN effect of the Delta32 mutant. It was abolished by certain deletions and by mutations of cysteine residues preventing formation of a disulfide link between the first and second extracellular loops, suggesting that conformation of Delta32 is important for its interaction with CCR5. To circumvent this problem, we used chimeric forms of the Delta32 and wild type CCR5, consisting in substitutions with homologous domains from the mouse CCR5. All chimeric full-length receptors were expressed at the cell surface and were functional for interaction with HIV-1 or with a chemokine ligand, when assayed. The TDN effect was only observed if both the TM3 domain in CCR5 and the TM4 domain in Delta32 were from human origin, whereas the rest of the proteins could be from either origin. This suggests that the TDN effect involves some form of interaction between these transmembrane domains. Alternatively, but less likely to us, substitutions in TM4 could affect the conformation of CCR5 in the endoplasmic reticulum but not at the cell surface. However that may be, it seems that the TDN effect of the Delta32 mutant has no bearing to the issue of CCR5 dimerization and to its possible role in the processing of the receptor to the cell surface.

Amino Acid Sequence↗

Palmitoyl derivatives of GpMBP epitopes: T-cell response and peptidases susceptibility.

We report for the first time the immunoadjuvant effects of lipoconjugation of peptide antigens in an in vitro system by using CD4+ T-cells. The lipopeptides obtained by conjugating a palmitoyl moiety at the N(alpha)-terminal of Gln(74) or at the epsilon-NH(2) of Lys(75) of GpMBP(74-85) induced increased T-cell responsiveness compared to the native nonlipidated peptide. On the other hand, lipoderivatives of GpMBP(82-98) did not increase the T-cell response, demonstrating that the superagonist inducing effect of lipoconjugation is epitope-specific. Digestion of the two native peptides with cathepsin D and L, both implicated in antigen processing, and with a complete lysosomal fraction of a EBV-transformed B cell line shows that GpMBP(74-85) is resistant to cellular proteases, while GpMBP(82-98) is easily digested by these enzymes. These results suggest that the first prerequisite for increasing the T-cell response by lipoconjugation is the stability of the native peptide to peptidases, providing an important insight into the understanding of the immunoadjuvant effect of lipoderivative antigens.

Animals↗

[Pelvic ganglioneuroma. Case report].

Ganglioneuroma is a neurogenic tumor originating from autonomic ganglia. It most commonly occurs in patients younger than 20 years with a slight predominance of females. The pelvic localization is rare. Imaging can lead to diagnosis but it is not specific. The diagnosis can only be confirmed by the pathologic study. The authors report one case of pelvic ganglioneuroma diagnosed in an 11-year-old child who also had hypertension and renal failure.

Acute Kidney Injury↗

A synthetic glycopeptide of human myelin oligodendrocyte glycoprotein to detect antibody responses in multiple sclerosis and other neurological diseases.

Glycopeptides of hMOG(30-50) containing a glucosyl moiety on the side-chains of Asn, Ser or Hyp at position 31 were synthesised. Antibody titres to hMOG(30-50) and to its glucoderivatives were measured by ELISA in sera of patients affected by different neurological diseases. Anti-hMOG(30-50) antibodies were detected only using the glycopeptide [Asn31(N-Glc)]hMOG(30-50).

Amino Acids↗

[Diabetic fibrous mastopathy].

Diabetic fibrous mastopathy was first described in 1984. This mastopathy usually occurs in patients with autoimmune disorders and often occurs in patients with insulin-dependent diabetes. Little is known about this benign condition. Clinically and radiologically, this entity may simulate malignancy. The presence of an underlying auto-immune disorder or diabetes may suggest the correct diagnosis. The authors report two cases of fibrous mastopathy and suggest that core biopsy could replace surgical biopsy for diagnosis.

Adult↗

An in vivo, ex vivo and in vitro comparative study of activity of copper oligopeptide complexes vs Cu(II) ions.

The tetrapeptide-Cu(II) complex H-(l-His-Gly)2-OH/Cu(II), indicated as L-Cu(II), has been investigated, as compared to the Cu(II) inorganic salt CuSO4, for its antioxidative and anti-inflammatory properties under a panel of experimental conditions. Both inorganic and organic Cu(II) compounds showed comparable activities in vitro and ex vivo by: (i) protecting, in a dose-dependent manner, rat brain homogenates from Fe(III)/ascorbate- or haemoglobin-induced lipid peroxidation; (ii) inhibiting the superoxide-mediated ferricytochrome c reduction by activated macrophages. CuSO4 and L-Cu(II) also exhibited similar anti-inflammatory effects in vivo by reducing significantly the extent of carrageenan-induced edema in the rat paw. The activities of the two compounds diverged strikingly only in the xanthine/xanthine oxidase system at low phosphate buffer concentration. L-Cu(II) decreased the rate of NBT reduction by superoxide in a true SOD-like fashion without affecting urate production. Instead, Cu(II) ions caused the rapid xanthine oxidase inactivation thus inhibiting both urate and superoxide production; this effect might be ascribed to the superoxide-mediated generation of the strong oxidant Cu(III) and its interaction with the enzyme. The administration of Cu(II), whether complexed with linear oligopeptides or as an inorganic salt, to animals or tissue extracts, conferred protection against oxidation and ought, conceivably, to interact with endogenous biological molecules and form highly bioavailable complexes which serve, subsequently, as the real scavengers. Moreover, the claimed prominent scavenger activities of Cu(II)-oligopeptide complexes over inorganic copper ions could be realised only in very simple in vitro systems through mechanisms which, although of biochemical interest, are unlikely to be of physiopathological significance.

Animals↗

Histidyl-glycyl containing peptides. Characterization complexation properties of H(L-His-Gly)2-R with hydrogen and alkali metal ions in the gas phase.

The two histidyl-glycyl containing peptides, H(L-His-Gly)2-OH and its methyl ester (H(L-His-Gly)2-OCH3, have been structurally characterized by liquid secondary-ion mass spectrometry. Both high-internal-energy ion fragmentations produced in the source and metastable decompositions occurring in the first field-free region have been studied. The mass spectra show the presence of y-, a- and b-type ions, a1 being the most abundant fragment ion. The metastable decompositions are dominated by the loss of a water molecule and by y-type ions. The interactions of the two peptides with alkali metal ions (Li, Na, K) have been evaluated both by normal mass spectrometry and by tandem mass spectrometry to obtain selected daughter-ion spectra. The occurrence of mono-, bi- and trimetallated species has been detected in the gas phase. While, in the case of the protonated species, y-type ions are predominant, in the presence of an alkali metal ion (Cat), they show lower abundances (Cat = Li) or are absent (Cat = Na, K) both in the mass spectra produced in the source and in metastable decompositions. In most of these cases, a very intense low-internal-energy ion, which is represented by [a3 + Cat - H]+ and which can be produced by interaction of the metal with a deprotonated amide nitrogen, is recorded. This mechanism should be favored by the ¿anchoring¿ effect exerted by the imidazole ring of the histidine which promotes interaction with metals. Other metastable decompositions yield abundant [b3 + Cat - H]+ ions or involve the loss of the side-chain of the histidine. The formation of [b3 + Cat +OH]+ ions, observed only in the case of the free acid peptide, is due to the interaction of the metal ion with the C-terminus carboxyl group. Bi- and trimetallated species have also been detected in the gas phase and characterized.

Amino Acid Sequence↗

[Anatomo-clinical characteristics of ovarian fibrothecal tumors. 19 cases over 12 years: 1981-1992[].

The quasi-constantly benign nature of fibrithecomas of the ovary has been known for many years. However, there have been very few studies of their incidence and clinical characteristics. The aim of this study, based upon 19 cases of fibrothecal tumours of the ovary operated upon at the Rabta maternity unit during a 12 year period, is to give an idea as to epidemiological factors, diagnostic conditions and treatment methods used among the women studied.

Adult↗

[Pregnancy following female surgical sterilization. A study apropos of 38 cases].

A study of 38 cases of pregnancy that occurred after sterilisation between 1st January 1981 and the 30th September 1987 at the Maternity and Neonatology Department of La Rabta, Tunis. This complication is rare because the overall global figure for failure is 7.1/1000. This is what is found in the literature. When we came to analyse the failures we found there were two groups: 15% of these failures were in women who had been sterilised correctly. This also happens when women have been sterilised with the Yonn ring as with Pomery's ligation technique. In this case when patients become pregnant there is a big chance of their being ectopic (2 tubal pregnancies as against 5 intrauterine pregnancies). 85% of failures were due to technical faults. They particularly happen with laparoscopic sterilisation (85%). They are usually due to lack of experience on the part of the operator. In any case patients do not like it; in fact 73.7% of the patients asked for a termination of the pregnancy and sterilisation was repeated in 87% of the cases.

Adult↗

[Abdominal pregnancy, a rare anatomoclinical entity. 4 case reports (1981-1990)].

The opportunity is taken, on the basis of 4 cases of abdominal pregnancy and a review of the literature, to attempt to analyse the various aspects of this increasingly rare pathology. Its incidence is low, being evaluated by our own study at 4/85 757 deliveries, i.e.: 1/21 439 deliveries collected at the Maternity and Neonatology centre of Rabta Tunis during a 10-year period (1981-1990). The essential epidemiological factor is the low socio-economic and cultural status seen in the patients studied. Clinical signs were predominated by metrorrhagia, abdominal pain, disturbed intestinal function and fetal death in utero. The delay in diagnosis explains the onset of frequent fetal complications in the form of fetal death in utero (3 cases out of 4) and of various fetal malformations. Ultrasonography is the essential investigation enabling diagnosis in the presence of clinical suspicion. Surgery is obligatory, excluding any attempt in the majority of cases at extraction of the placenta, which is left in place.

Adult↗

X-ray structure analysis of 3,11,17-trioxoandrostane-5 alpha-carbonitrile and of 17 alpha-ethoxycarbonyloxy-3-oxoandrost-4-ene-17-carbonitrile.

The crystal and molecular structures of the title compounds were determined by x-ray diffractometric analysis. Torsion angles and puckering parameters are reported for both compounds. In 1 the 5 alpha-cyano group influences the A-ring conformation. The carbonate ester 3 crystallizes in the monoclinic P2(1) space group with two molecules (I and II) in the asymmetric unit. The D-ring conformation is to some extent different between I and II.

Androstanes↗

[Pelvic hydatid cyst and pregnancy. Four cases].

The association of pelvic hydatid cyst with pregnancy is rare. We collected 4 cases between 1981-1990. Our incidence is of 1/30000 deliveries. The diagnosis was suggested in 3 cases by the patient's country of origin and previous history of extra-pelvic hydatid disease. It is confirmed by ultrasonography, which is still the first choice examination. During the 3 pregnancies managed to term, we did not find any modification in the cyst. One patient had vaginal delivery twice; however complications, sometimes fatal, are reported in the literature. The time for surgery and the mode of delivery are discussed because of the rarity of this association.

Adult↗

[Results at the Rabta Tunis Maternity and Neonatology Center of the surgical treatment of genital prolapse. 193 cases in 7 years (1982-1988)].

The authors report their experience in the treatment of 193 cases of genital prolapse treated surgically in the Rabta Tunis Maternity and Neonatology Unit during a 7 year period between January 1st 1982 and December 31st 1988. The epidemiological characteristics of the study population were dominated by the following factors: advanced age (mean age 54); multiparity (80 per cent of cases); 65.8 per cent of women were post-menopausal. The commonest association of lesions was triple prolapse, present in 78 per cent of cases. Stress incontinence of urine (SIU) was a common feature (59 per cent of cases). Treatment preference was for vaginal hysterectomy combined with anterior colporrhaphy and posterior perineorrhaphy (73.5 per cent). The Kelly Marion operation was often used for SIU (89 per cent of cases) and gave satisfactory results in 73 per cent of cases.

Adult↗

Highly efficient synthesis of steroid-17-spiro-5'-oxazolidine-2',4'-diones from 17-keto steroids.

Spiro[androst-4-en-17 alpha,5'-oxazolidine]-2',3,4'-trione 8a and spiro[androst-4-en-17 alpha,5'-oxazolidine]-2',3,4',11-tetraone 8b, two potentially bioactive spiranes, were prepared from the parent 17-ketones in four steps (64% and 49.5% yield, respectively). The key intermediates were the hydroxyimidates 5a and 5b, which easily underwent cyclization to the corresponding spirooxazolinone 4'-enol ethers when treated with alkylchlorocarbonates. The respective N-amyl derivatives of the spiranes 8a and 8b were obtained with n-pentyl bromide in the presence of KF. A new method for the synthesis of steroid 17 alpha-hydroxy-17-carboxyesters and 17 alpha-hydroxy-17-carboxamides is described. Attempts to synthesize the title compounds from these products were unsuccessful.

17-Ketosteroids↗

[Von Recklinghausen's neurofibromatosis and pregnancy. Apropos of a case].

Having seen a personal case and having reviewed the literature, we clarify the details when neurofibromatosis and pregnancy occur together. Few cases of this combination of conditions have been reported. The complications can be serious and have led some authors to suggest that the pregnancy should be terminated in every case and that the patient should be sterilised. Sometimes the only risk is hypertension of pregnancy, which is what occurred in our case. Its progress was benign and according to the literature this seems to be the most usual outcome. All the same, because it is possible that complications can occur in any case of neurofibromatosis in pregnancy, pregnant women with neurofibromatosis should be placed in a high-risk group which has to be watched very carefully.

Adult↗

[Neonatal and maternal prognosis in the delivery of a single large fetus at term. Apropos of 497 cases].

We have studied 497 deliveries of large fetuses over a period of two years from 1/1/86 to 31/12/87 in the Maternity Unit of Aziza Othmana. We understand by the term "large fetus" the delivery of a baby weighing 4 kg or more. From this study it appears that: the overall incidence is 6.8% of the deliveries; fetal macrosomia occurs much more frequently in multiparous women who are older; 18.4% of these had large babies previously; diabetes occurred in only 11% of the population studied. We study in this article the complications due to fetal macrosomia during pregnancy, labour and following the delivery. We unfortunately have to report: at fetal level: the mortality is 1.2% and the morbidity is 3.6%; at maternal level: the mortality is nil, the morbidity is 4.6%. Several factors affecting the prognosis were analysed in order to look at the subject from the aetiological and prophylactic points of view (these were the method of delivery, the obstetrical factor, the maternal factors, the factors linked to labour, the factors linked to the pregnancy and other factors).

Adult↗