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Biomedical subjects

M Yebra

Publications and source records attributed to M Yebra.

At least 19 recordsLinked to original sources
PubMed2003

Irreversible coma, ergotamine, and ritonavir.

We report the first case in the medical literature (to our knowledge) of a patient with human immunodeficiency virus infection who was being treated with ritonavir and developed signs of severe vascular involvement and irreversible coma after the administration of 3 mg of ergotamine tartrate.

Adult↗
PubMed2000

[Coxiella burnetii endocarditis: long-term clinical course in 20 patients].

INTRODUCTION AND OBJECTIVES: Coxiella burnetii is a causative agent of increasingly frequent subacute infective endocarditis, and is associated with elevated morbimortality. Our aim in the present study was to assess the clinical, serological and therapeutic long-term evolution of 20 patients with Coxiella burnetii endocarditis. METHODS: Twenty patients (13 male and 7 female, age 42 +/- 10 years) admitted between 1982 and 1996 were retrospectively studied. All of them fulfilled the Duke criteria modified by Raoult for Q fever endocarditis. RESULTS: Endocarditis involved prosthetic and native valves in 14 and 6 patients, respectively. All patients except one received antibiotic treatment. Patients treated with doxycycline in monotherapy showed worse evolution than those treated with doxycycline in combination with other antibiotics. Valve replacement was performed in 15 patients, due to prosthetic dysfunction in most of them. The overall mortality was 40% (8 patients). At follow-up of 74 months (range 19-156) (mean 74 +/- 47) all patients showed persistent high levels of phase I antibodies. At follow-up of 15 to 65 months (32 +/- 30) antibiotic treatment was suspended in five patients because they were asymptomatic and without microbiologic findings of valvular endocarditis. CONCLUSIONS: Q fever endocarditis was associated with severe complications, which often required valve replacement. All patients showed persistent high serological titers of Coxiella burnetii endocarditis without other signs of active infection. This finding raises the issue of suspending antibiotic treatment in patients with negative microbiologic findings and questions the persistence of abnormal serology as a monitor of treatment efficacy.

Adult↗
PubMed1999

Urokinase-type plasminogen activator binding to its receptor stimulates tumor cell migration by enhancing integrin-mediated signal transduction.

Urokinase-type plasminogen activator (uPA) and its receptor (uPAR) participate in matrix degradation and cell migration by focusing proteolysis and functioning as a signaling ligand/receptor complex. uPAR, anchored by a lipid moiety in the membrane, is thought to require a transmembrane adapter to transduce signals into the cytoplasm. To study uPAR signaling, we transfected the prostate carcinoma cell line LNCaP, which does not express endogenous uPA or uPAR, with a uPAR encoding cDNA, resulting in high-level surface expression. We studied migration of these cells on fibronectin, which is mediated by the integrin alpha5beta1. Ligation of uPAR with uPA or its amino-terminal fragment enhanced haptotactic migration to fibronectin. In cells on fibronectin, but not on poly-l-lysine, ligation of uPAR also resulted in tyrosine phosphorylation of several proteins, including two proteins involved in integrin signaling, focal adhesion kinase and the crk-associated substrate p130(Cas). Furthermore, after uPAR ligation, uPAR was co-immunoprecipitated with beta1 integrins from the detergent-insoluble fraction of cell lysates. Thus, our data suggest that uPAR occupancy results in an interaction between uPAR and integrins and a potentiation of integrin-mediated signaling, which leads to enhanced cell migration.

Cell Adhesion↗
PubMed1999

Sustained response to interferon-alpha or to interferon-alpha plus ribavirin in hepatitis C virus-associated symptomatic mixed cryoglobulinaemia.

BACKGROUND: Hepatitis C virus (HCV) infection has been associated with mixed cryoglobulinaemia. AIM: To investigate the efficacy of anti-viral therapy on the eradication of HCV and its clinical manifestations in patients with HCV-associated symptomatic mixed cryoglobulinaemia. PATIENTS AND METHODS: 18 out of 32 patients with symptomatic mixed cryoglobulinaemia (MC group) received a 12-month course of interferon (3 MU three times a week, subcutaneously). Nonresponders or relapsers to this therapy were treated with interferon plus ribavirin (1200 mg/day, orally) for 12-months. 226 patients with HCV infection and without cryoglobulins were studied in comparison (Hepatitis C group). Serial quantification of serum HCV-RNA and cryoglobulins were performed. RESULTS: In the MC group, 10 out of 18 patients (55%) receiving interferon showed an end of treatment response, but at the end of follow-up, only five (28%) patients had a sustained response. In the hepatitis C group, 91 patients (47%) showed an end of treatment response but only 42 (20%) a sustained response. In the MC group alanine transaminase, cryocrit and rheumatoid factor decreased significantly in responders, with an improvement or disappearance of the MC-associated clinical manifestations. Alanine transaminase, cryocrit and rheumatoid factor increased in the relapsers and the clinical manifestations reappeared. Nonresponders and relapsers to interferon in the MC group were retreated with interferon plus ribavirin. Five out of eight nonresponders showed a end of treatment response but it was sustained in three of them. In the relapsers, treatment with combined therapy achieved a sustained response in four out of the five patients (80%). CONCLUSIONS: Interferon as monotherapy or combined with ribavirin is a safe and effective treatment in patients with HCV-associated MC. The presence of cryoglobulins does not affect the response to anti-viral treatment in patients with HCV infection. The eradication of HCV is associated with an improvement or disappearance of MC-associated clinical manifestations.

Antiviral Agents↗
PubMed1998

[Detection of human herpesvirus 8 in patients with Kaposi's sarcoma or Castleman's disease associated with AIDS].

A new herpesvirus provisionally termed as KSHV or HHV-8 has been detected in lesions from AIDS-based Kaposi's sarcoma (KS) and from other KS clinical forms, and also in other tumors such as body cavity-based lymphomas or Castleman's disease (CD). We have assessed the presence of this novel herpesvirus in specimens from patients diagnosed with either AIDS and KS or AIDS and CD. DNA samples from skin lesions and peripheral blood obtained from 8 patients diagnosed with AIDS, seven with KS and one with multicentric CD were analyzed; skin specimens and peripheral blood samples from volunteer blood donors or from KS and CD free HIV seronegative patients were used as controls. Detection of the virus was done by PCR amplification of KS330 region, one of the HHV-8 sequences first reported. All skin lesions analysed tested positive for KS330; peripheral blood samples from 5 of the patients, including the one diagnosed with CD, showed also the virus sequence. All skin specimens and peripheral blood samples from controls were negative. From our results it can be concluded that the novel herpesvirus HHV-8 can also be detected in patients with AIDS-associated KS and AIDS-associated CD in Spain.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Distribution of IgA subclass response to Coxiella burnetii in patients with acute and chronic Q fever.

The progression of Coxiella burnetii infection to acute or chronic Q fever has been attributed to biological characteristics of the bacterium and to the host immune response. We measured whether serum levels of total and specific subclasses IgA1 and IgA2 could be correlated with the course of disease in acute and chronic Q fever infections, and with the occurrence of endocarditis. In patients with chronic infection, total IgA2 levels were significantly increased. Q-fever-specific IgA1 antibodies were detectable in both acute and chronic infections, but only patients with endocarditis had IgA2 antibodies to C. burnetii phase II antigens. These findings indicate that the measurement of IgA subclasses may be a useful aid in the serological diagnosis of Q fever. Our results reinforce the idea that immunologically mediated host factors are important in the pathogenesis of Q fever and in the disease outcome of this infection.

Acute Disease↗
PubMed1998

Three cases of tuberculosis after heart transplantation in Spain.

Three cases are presented of tuberculosis occurring in a series of 410 heart transplant recipients in a Spanish hospital, representing a rate of 0.73%. Twenty-eight cases reported in the literature are also reviewed. In most series reported, tuberculosis occurred in a small percentage of heart transplant recipients, the average rate being 1.25%. Compared to the general population, a higher percentage (28%) of extrapulmonary and disseminated forms of the disease is seen in these patients. Although a cure without recurrence can usually be achieved with a conventional anti-tuberculous antibiotic regimen, the disease is still associated with a significant mortality rate of 11%. Guidelines for the early diagnosis and treatment of these patients are discussed.

Aged↗
PubMed1998

[Visceral leishmaniasis in immunocompromised patients].

OBJECTIVE: Most patients who developed visceral leishmaniasis (VL) in our country are ímmunocompromised (IC) host, frequently HIV-infected patients. One objective was to know if there were differences about the clinical manifestations, diagnostic tests or prognosis in IC patients who were infected or not with HIV (HIV+ and HIV-, respectively). Also we wonder if some features were associated with death during the initial episodes of VL. METHOD: We studied 16 IC patients with VL, 9 were VIH+ and 7 were VIH-. Most frequently observed findings were fever (94%), splenomegaly (81%), hepatomegaly (69%), and constitutional syndrome (50%). HIV+ patients had symptoms during a lapse of time (70 +/- 78 days) larger than the VIH- cases had (17 +/- 12 days, p < 0.05). RESULTS: We performed a serology to Leishmania sp in 15 cases (94%) and were positive in 13 patients (77% in HIV+ and 100% in VIH patients). Seven patients (44%, 4 VIH- and 3 VIH+) died during the initial episode of VL. Nine patients (66%) who survived to it were followed-up during 68 +/- 49 months. Seven patients (4 VIH+ and 3 VIH-) showed several relapses (2.5 +/- 1.6 relapses/patient) through the follow-up. The patients who died during the initial episode had more frequently (p < 0.05) concentrations of albumin below 3 g/dl or of globulins below 4 g/dl, than the survivors had. The CD4+ lymphocyte counts in HIV+ patients were lower in patients who died during the initial episode of VL (19 +/- 15/mm) than in survivors (108 +/- 67/mm3, p = 0.07).

AIDS-Related Opportunistic Infections↗
PubMed1996

Requirement of receptor-bound urokinase-type plasminogen activator for integrin alphavbeta5-directed cell migration.

The urokinase plasminogen activator (uPA) interacts with its cell surface receptor (uPAR), providing an inducible, localized cell surface proteolytic activity, thereby promoting cellular invasion. Evidence is provided for a novel function of cell surface-associated uPA.uPAR. Specifically, induction of cell surface expression of uPA. uPAR by growth factors or phorbol ester was necessary for vitronectin-dependent carcinoma cell migration, an event mediated by integrin alphavbeta5. Cell migration on vitronectin was blocked with either a soluble form of uPAR, an antibody that disrupts uPA binding to uPAR, or a monoclonal antibody to alphavbeta5. Moreover, plasminogen activator inhibitor type 2 blocked this migration event but did not affect adhesion, suggesting a direct role for uPA enzyme activity in this process and that migration but not adhesion of these cells is regulated by uPA.uPAR. Growth factor-mediated induction of uPA.uPAR on the carcinoma cell surface promotes a specific motility event mediated by integrin alphavbeta5, since cells transfected with the beta3 integrin subunit expressed alphavbeta3 and migrated on vitronectin independently of growth factors or uPA.uPAR expression. This relationship between alphavbeta5 and the uPA.uPAR system has significant implications for regulation of motility events associated with development, angiogenesis, and tumor metastasis.

Cell Movement↗
PubMed1996

Suppression of p53 activity and p21WAF1/CIP1 expression by vascular cell integrin alphaVbeta3 during angiogenesis.

Induction of p53 activity in cells undergoing DNA synthesis represents a molecular conflict that can lead to apoptosis. During angiogenesis, proliferative endothelial cells become apoptotic in response to antagonists of integrin alphavbeta3 and this leads to the regression of angiogenic blood vessels, thereby blocking the growth of various human tumors. Evidence is presented that administration of alphavbeta3 antagonists during angiogenesis in vivo selectively caused activation of endothelial cell p53 and increased expression of the p53-inducible cell cycle inhibitor p21WAF1/CIP1. In vitro studies revealed that the ligation state of human endothelial cell alphavbeta3 directly influenced p53 activity and the bax cell death pathway. Specifically, agonists of endothelial cell alphavbeta3, but not other integrins, suppressed p53 activity, blocked p21WAF1/CIP1 expression, and increased the bcl-2/bax ratio, thereby promoting cell survival. Thus, ligation of vascular cell integrin alphavbeta3 promotes a critical and specific adhesion-dependent cell survival signal during angiogenesis leading to inhibition of p53 activity, decreased expression of p21WAF1/CIP1, and suppression of the bax cell death pathway.

Allantois↗
PubMed1995

Induction of carcinoma cell migration on vitronectin by NF-kappa B-dependent gene expression.

Integrin alpha v beta 5 promotes FG carcinoma cell adhesion to vitronectin yet requires protein kinase C (PKC) activation for migration on this ligand. Here we report that this PKC-dependent cell motility event requires NF-kappaB-dependent transcription. Specifically, a component within nuclear extracts prepared from PKC-stimulated FG cells exhibited a significant increase in binding activity to a synthetic oligonucleotide containing a consensus kappa B sequence. These nuclear DNA-binding complexes were shown to be comprised of p65 and p50 NF-kappaB/rel family members and appeared functionally active because they promoted transcription of a reporter construct containing a kappa B site. The NF-kappa B activation event was directly linked to the alpha v beta 5 motility response because the NF-kappa B-binding oligonucleotide, when introduced into FG cells, inhibited cell migration on vitronectin but not on collagen and had no effect on cell adhesion to either ligand. These results suggest that the detected DNA-binding complexes interact with kappa B transcriptional elements to regulate gene expression required for alpha v beta 5-dependent cell motility on vitronectin.

Base Sequence↗