Biomedical subjects

Jose Rubio

Publications and source records attributed to Jose Rubio.

5 recordsLinked to original sources

PubMed2004

Impact of fibronectin fragments on the transendothelial migration of HIV-infected leukocytes and the development of subendothelial foci of infectious leukocytes.

Leukocyte infiltrates that can serve as viral reservoirs, and sites for viral replication are found in many organs of HIV-1-infected patients. Patients whose blood leukocytes migrate across confluent endothelial monolayers ex vivo and transmit infectious virus to mononuclear leukocytes (MNLs) lodged beneath this endothelial barrier have a worse prognosis. We evaluated the ability of 110- to 120-kDa fibronectin fragments (FNf), which are found in the blood of >60% of HIV-1-infected patients, to stimulate transendothelial migration and drive productively infected MNLs into a potential perivascular space. FNf induced MNLs to release TNF-alpha in a dose-dependent fashion; the resulting increase in lymphocyte and monocyte transendothelial migration could be blocked with soluble TNF receptor I. Rather than penetrate deeply into the subendothelial matrix, as is seen with untreated controls, FNf-treated MNLs clustered just below the endothelial monolayer. Treatment with FNf during migration increased subsequent recovery of HIV-infected cells from the subendothelial compartment. FNf treatment also significantly increased the numbers of HLA-DR(bright), dendritic-type cells that reverse-migrated from the subendothelial depot to the apical endothelial surface 48 h after migration. Fibronectin fragments can be produced by viral and host proteases in the course of inflammatory conditions. The ability of FNf to stimulate transendothelial migration of HIV-1-infected MNLs may help to explain the dissemination of this infection into cardiac, renal, and CNS tissues.

Animals↗

PubMed2004

The optimum timing of radical cystectomy for patients with recurrent high-risk superficial bladder tumour.

OBJECTIVE: To establish the optimum time of radical cystectomy (RC) for patients with recurrent high-risk superficial bladder tumours after the failure of intravesical therapy. PATIENTS AND METHODS: Among 318 patients with transitional cell carcinoma treated with RC and with no neoadjuvant therapy, there were 46 with clinical stage Ta, T1 or Tis refractory to transurethral resection associated with intravesical therapy. These patients had at least one of: (i) high-risk superficial bladder tumours after failure of two consecutive induction courses of intravesical therapy; (ii) superficial bladder tumours with prostatic stromal invasion; (iii) superficial bladder tumours with mucosa/ducts involvement after failure of one course of intravesical therapy; (iv) uncontrolled superficial tumours with transurethral resection associated or not with intravesical therapy. Progression and cause-specific survival of these patients were compared to those with muscle-invasive tumours. Univariate and multivariate analyses of predictive factors for cause-specific survival were also used in patients with superficial tumours. The incidence of significant prognostic factors was compared in both superficial and muscle-invasive tumours, as were the progression pattern and survival. RESULTS: The progression-free and cause-specific survival of patients with superficial tumours was 54% and 67%, respectively, with no significant difference from those with muscle-invasive tumours. In multivariate analysis, positive lymph-nodes and prostatic stromal invasion were significant and independent variables for survival. The incidence of positive lymph nodes was 15% vs 30% (P < 0.05) and of stromal invasion was 32% vs 1.5% (P < 0.001) in patients with superficial and muscle-invasive tumours, respectively. Accounting for the progression pattern in patients with superficial tumours, extravesical urothelial recurrence prevailed over local or distant recurrences (30% vs 15%), whereas in patients with muscle-invasive tumours the opposite occurred (5% vs 33%, respectively). The cause-specific survival of patients with superficial tumour and prostatic stromal invasion was one of three, and in those who developed extravesical urothelial recurrence was 28.5%. CONCLUSION: In patients with recurrent high-risk superficial bladder cancer after intravesical therapy, our criteria for RC were inappropriate, and patients had a survival rate similar to those with muscle-invasive tumours. RC might have been used too late, as there was a high incidence of prostatic stromal invasion and extravesical urothelial recurrence after RC. Both events seem to be responsible of the low cause-specific survival. Predictive factors for progression are needed to indicate early RC in patients with recurrent high-risk superficial tumours. From a previous analysis the pathological pattern of the clinical lack of response (T1, G3, bladder carcinoma in situ and prostate involvement) to intravesical therapy evaluated at 3 months might be important for predicting progression, and an early RC at that time might be useful.

Aged↗

PubMed2004

Inflammation and ischemia: macrophages activated by fibronectin fragments enhance the survival of injured cardiac myocytes.

Proteolytic enzymes, released early in the course of an inflammatory response, hydrolyze fibronectin, producing fragments of the parent molecule that alter monocyte phenotype and migratory behavior. Here we test the hypothesis that macrophages, stimulated by the dominant 110-120 kd fibronectin fragments (FNf), as are found in lymphatic fluid draining sites of cardiac ischemia-reperfusion injury, produce factors that promote the survival of injured parenchymal cells. Rat splenic macrophages stimulated in vitro with purified FNf produced soluble factors that protected hypoxic rat cardiac myocytes from death by apoptosis. Addition of blocking antibodies specific for tumor necrosis factor-alpha(TNF-alpha), fibroblast growth factor-1 (FGF-1), insulin-like growth factor I (IGF-I), and leukemia inhibitory factor (LIF) partly reduced the protection against apoptosis provided to hypoxic cardiac myocytes by cell-free culture supernatants from FNf-stimulated macrophages. Complete blockade of this protection was achieved by a combination of antibodies specific for FGF-1, IGF-I, and LIF. Stimulation of human monocyte-derived macrophages in vitro with FNf significantly increased their output of TNF-alpha, FGF-1, IGF-I, and LIF. These results suggest that tissue degradation products, released in the early hours of an inflammatory response, stimulate tissue-infiltrating macrophages to protect injured but still viable parenchymal cells from death by apoptosis.

Animals↗

PubMed2001

Interaction between human polymorphonuclear leukocytes and Streptococcus milleri group bacteria.

Because Streptococcus milleri group (SMG) bacteria--Streptococcus constellatus, Streptococcus intermedius, and Streptococcus anginosus--exhibit a striking propensity to cause abscesses, the interaction of these organisms with human polymorphonuclear leukocytes (PMNL) was examined. After incubation in pooled normal human serum, SMG stimulated less chemotaxis than did Staphylococcus aureus, in contrast to viridans streptococci, which caused greater chemotaxis than did S. aureus. PMNL ingested greater numbers of SMG and viridans streptococci than S. aureus but killed these organisms more slowly and less completely. Relative resistance to killing by PMNL is expected in organisms that cause abscesses, and inhibition of chemotaxis may contribute to pathogenicity, because delayed arrival of PMNL gives a head start to proliferating bacteria. This study helps explain the capacity of SMG to cause abscesses. It is unclear, however, why viridans streptococci, bacteria that rarely produce abscesses, share some of these same properties.

Abscess↗

PubMedDate not supplied

Disruption of basement membrane, extracellular matrix metalloproteinases and E-cadherin in renal-cell carcinoma.

UNLABELLED: A retrospective study was performed to determine the prognostic value of Basement Membrane (BM) integrity, Matrix Metalloproteinases (MMPs) and E-Cadherin expression in renal cell carcinoma (RCC). MATERIALS AND METHODS: An immunohistochemical study on laminin and collagen IV, MMPs 1 and 2, and E-Cadherin was carried out on 71 RCCs. BM fragmentation was considered taking 75% as a cut-off. MMP 1 and MMP2 immunostaining, as well as E-Cadherin was considered taking 25% as a cut-off. RESULTS: An inverse relationship was seen between E-Cadherin with laminin, collagen IV and MMPs. More than 75% loss of laminin, collagen IV and E-Cadherin, as well as higher expression of MMPs, were associated with symptoms, tumoral size and worse grade. Loss of collagen IV and E-Cadherin were of prognostic value. CONCLUSION: Both BM and E-Cadherin are good prognostic markers. MMPs patterns show a relationship between BM proteins and E-Cadherin, but evaluation is more time-consuming and provide no better prognostication; consequently they are not useful in routine clinical applications.

Basement Membrane↗