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Biomedical subjects

A Azzi

Publications and source records attributed to A Azzi.

At least 289 records · Page 16Linked to original sources
PubMedDate not supplied

Structural and functional alterations induced in the mitochondrial cytochrome b-c1 complex by N,N'-dicyclohexylcarbodiimide.

N,N'-Dicyclohexylcarbodiimide (DCCD) inhibits the activity of ubiquinol-cytochrome c reductase in the isolated and reconstituted mitochondrial cytochrome b-c1 complex. In proteoliposomes containing b-c1 complex DCCD inhibits equally electron flow and proton translocation catalyzed by the enzyme. In both isolated and reconstituted systems the inhibitory effect is accompanied by structural alterations in the polypeptide pattern of the enzyme consistent with cross-linking between subunits V and VII. The kinetics of inhibition of enzymic activity correlates with that of the cross-linking, suggesting that the two phenomena may be coupled. Binding of [14C] DCCD to both isolated and reconstituted enzyme was also observed, though it was not correlated kinetically with the inhibition.

Animals↗
PubMedDate not supplied

Isolation of influenza A(H3N2) virus with "O"-->"D" phase variation.

We report the isolation of two influenza A(H3N2) virus strains which were unable, in the first passages in MDCK cell culture, to agglutinate chicken erythrocytes, though reacting with guinea pig and turkey red blood cells. This observation demonstrates that the occurrence of this phenomenon is not exclusive to influenza A(H1N1) viruses, as previously reported. In order to investigate the molecular basis of this phenomenon, we analysed the nucleotide sequence of the HA-1 region, presumed to be involved in the switch of haemagglutination properties, from the virus present in the original samples and in the corresponding strains isolated and cultivated in MDCK cells and in embryonated eggs. The substitution of amino acid 138 (Ala-->Ser) in MDCK cells could be related to the change in haemagglutination characteristics.

Amino Acid Sequence↗
PubMedDate not supplied

3D-structure of human estrogenic 17beta-HSD1: binding with various steroids.

Human estrogenic dehydrogenase (17beta-HSD1) catalyses the last step in the biosynthesis of the active estrogens that stimulate the proliferation of breast cancer cells. While the primary substrate for the enzyme is estrone, the enzyme has some activity for the non-estrogenic substrates. To better understand the structure function relationships of 17beta-HSD1 and to provide a better ground for the design of inhibitors, we have determined the crystal structures of 17beta-HSD1 in complex with different steroids. The structure of the complex of estradiol with the enzyme determined previously (Azzi et al., Nature Structural Biology 3, 665-668) showed that the narrow active site was highly complementary to the substrate. The substrate specificity is due to a combination of hydrogen bonding and hydrophobic interactions between the steroid and the enzyme binding pocket. We have now determined structures of 17beta-HSD1 in complex with dihydrotestosterone and 20alpha-OH-progesterone. In the case of the C19 androgen, several residues within the enzyme active site make some small adjustments to accommodate the increased bulk of the substrate. In addition, the C19 steroids bind in a slightly different position from estradiol with shifts in positions of up to 1.4 A. The altered binding position avoids unfavorable steric interactions between Leu 149 and the C19 methyl group (Han et al., unpublished). The known kinetic parameters for these substrates can be rationalized in light of the structures presented. These results give evidence for the structural basis of steroid recognition by 17beta-HSD1 and throw light on the design of new inhibitors for this pivotal steroid enzyme.

17-Hydroxysteroid Dehydrogenases↗
PubMedDate not supplied

Anti-atherosclerotic effects of vitamin E--myth or reality?

Atherosclerosis and its complications such as coronary heart disease, myocardial infarction and stroke are the leading causes of death in the developed world. High blood pressure, diabetes, smoking and a diet high in cholesterol and lipids clearly increase the likelihood of premature atherosclerosis, albeit other factors, such as the individual genetic makeup, may play an additional role. Several epidemiological studies and intervention trials have been performed with vitamin E, and some of them showed that it prevents atherosclerosis. For a long time, vitamin E was assumed to act by decreasing the oxidation of LDL, a key step in atherosclerosis initiation. However, at the cellular level, vitamin E acts by inhibition of smooth muscle cell proliferation, platelet aggregation, monocyte adhesion, oxLDL uptake and cytokine production, all reactions implied in the progression of atherosclerosis. Recent research revealed that these effects are not the result of the antioxidant activity of vitamin E, but rather of precise molecular actions of this compound. It is assumed that specific interactions of vitamin E with enzymes and proteins are at the basis of its non-antioxidant effects. Vitamin E influences the activity of several enzymes (e.g. PKC, PP2A, COX-2, 5-lipooxygenase, nitric oxide synthase, NADPH-oxidase, superoxide dismutase, phopholipase A2) and modulates the expression of genes that are involved in atherosclerosis (e.g. scavenger receptors, integrins, selectins, cytokines, cyclins). These interactions promise to reveal the biological properties of vitamin E and allow designing better strategies for the protection against atherosclerosis progression.

Adult↗
PubMedDate not supplied

Parvovirus B19 infection of bone marrow in systemic sclerosis patients.

OBJECTIVE: To investigate the prevalence of human parvovirus B19 (B19) infection in the bone marrow of systemic sclerosis (SSc) patients. METHODS: Twenty-one consecutive SSc patients and 15 sex- and age-matched subjects without immunological rheumatic diseases were studied for: (i) the presence of circulating anti-B19 antibodies (anti-B19 IgG and IgM type and anti-B19 NS1 IgG) detected by means of standard methodologies, and (ii) B19 genomic sequences in sera and bone marrow biopsy specimens using a nested-PCR technique. RESULTS: The presence of B19 DNA was demonstrated in a significant percentage of bone marrow biopsies from SSc patients (12/21; 57%) and was never detected in the control group (p < 0.01). In no case was the B19 viremia observed, while serum anti-B19 NS1 antibodies, possible markers of B19 persistent infection, were more frequently detected in SSc patients than in controls (33% vs 13%). SSc patients with bone marrow B19 infection showed a shorter mean disease duration than B19-negative patients (5.6 +/- 4.2 vs 12.7 +/- 7.8 yrs; p < 0.01). CONCLUSIONS: This is the first demonstration of bone marrow B19 infection in a significant percentage of SSc patients. The possible etiopathogenetic role of B19 should be verified in a larger patients series and further investigated by means of molecular biology studies.

Adult↗
PubMedDate not supplied

[Polyomavirus BK-associated nephropathy after kidney transplantation].

Polyomavirus BK (BKV) infection has been lately recognized as a major cause of renal allograft dysfunction. BKV-related interstitial nephropathy (PVAN) may affect 1-10% of renal allograft recipients, occurring more frequently in the first 6 months after transplantation. Progression to irreversible allograft failure has been observed in up to 45% of all cases; thanks to increased PVAN awareness and improved diagnostic techniques, the rate of graft loss has lowered, more consistently in centres with active screening and intervention programs. PVAN pathogenesis is characterized by multiple synergizing factors, among which immunodepression plays a key role. PVAN diagnosis requires the evaluation of a renal biopsy showing polyomavirus cytopathic changes and confirming BKV through an ancillary technique such as immunohistochemistry. Given the focal nature of the disease, early diagnosis may be difficult to obtain. Thus, quantification of BKV-DNA in plasma has been suggested as surrogate marker for PVAN. To date, given the lack of controlled trials, there is no consensus on a 'standard' management of PVAN. However, evidence based on reported observations suggests that a step-wise reduction of immunosuppression, preceded by pulsed steroids in case of coexistent acute rejection, may improve outcomes. Additional options may be represented by drugs with antiviral activity, such as cidofovir, leflunomide or quinolones. Application of a preventive treatment based on viremia monitoring has been recently proposed.

Adrenal Cortex Hormones↗
PubMedDate not supplied

Aplastic crisis caused by B19 virus in a child during induction therapy for acute lymphoblastic leukemia.

A child undergoing induction therapy for acute lymphoblastic leukemia suffered an aplastic crisis associated with B19 virus infection. Good response to the antiblastic therapy led to a burst in erythropoiesis favoring high viral replication, which was responsible for strong erythroblastic inhibition and severe viremia. The patient's B19 antibody response became evident very late, probably because of the antiblastic effect of the therapy; nevertheless, recovery was complete in little more than a week, favored by B19 IgG transfusion with a red blood cell concentrate. This report suggests that immunosuppressed subjects, as well as those suffering from hemolytic anemia must also be considered "at risk" for aplastic crisis due to B19 infection.

Anemia, Aplastic↗