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Biomedical subjects

J Jordá

Publications and source records attributed to J Jordá.

15 recordsLinked to original sources

Unusual perforated appendicitis within umbilical hernia: CT findings.

We present the first imaging report of perforated appendicitis in an umbilical hernia. Computed tomography demonstrated a gas-forming abscess within an umbilical hernia and the cecum was found inside the hernial sac, with an inner relation to the abscess. Computed tomographic findings suggested appendicitis as possible diagnosis, which was confirmed at surgery. Physicians must consider appendicitis within the differential diagnosis of an abdominal abscess located near to the cecum, even at an unexpected location.

Appendicitis↗

A sustained activation of PI3K/NF-kappaB pathway is critical for the survival of chronic lymphocytic leukemia B cells.

The progressive rise of mature CD5+ B lymphocytes, despite the low proportion of proliferating cells, has led to the notion that B cell chronic lymphocytic leukemia (B-CLL) is primarily related to defective apoptosis. The microenvironment likely plays a prominent role because the malignant cells progressively accumulate in vivo, whereas they rapidly undergo spontaneous apoptosis when cultured in vitro. To assess microenvironment-mediated survival signals, B-CLL cells were cultured with a murine fibroblast cell line, Ltk-, with and without an agonistic antibody to CD40. Spontaneous apoptosis was associated with the loss of Akt and NF-kappaB activities. Interactions with fibroblasts sustained a basal level of Akt and NF-kappaB activities, which was dependent on phosphatidylinositol-3 kinase (PI3K). Constitutive activity of the PI3K pathway in B-CLL cells when cultured with fibroblasts prevented the downregulation of the prosurvival Bcl-2 family protein Bcl-xL and the caspase inhibitor proteins FLIPL and XIAP, and consequently caspase-3 activation and apoptosis. CD40 crosslinking in B-CLL cells did not further prevent murine fibroblasts-mediated apoptosis but induced cell proliferation, which was associated with an increase of Akt and NF-kappaB activation compared with cells cultured with fibroblasts alone. The PI3K pathway seems to play a pivotal role in B-CLL cell survival and growth.

Adult↗

Effect of N-acetylcysteine on the oxidative burst induced by phagocytosis of bacteria in human leukocytes.

The basal peroxide production and the oxidative burst induced by phagocytosis of opsonized E. coli was studied by flow cytometry using dihydrorhodamine 123. The human leukocytes were incubated in the absence and presence of N-acetylcysteine. The oxidative response to the phagocytosis of bacteria differed among cell populations. Thus, 90% of granulocytes and 50% of monocytes showed an oxidative burst in response to opsonized bacteria while less than 1% of lymphocytes showed a fluorescence signal. N-Acetylcysteine (4.7, 9.5, 19, 38 or 76 mM) produced a dose-dependent inhibition of the oxidative response to phagocytosis in the three cellular populations reaching almost complete inhibition for 76 mM. This protective effect of N-acetylcysteine against oxidative stress in leukocytes was obtained without cytotoxicity (assessed by flow cytometry with staining with propidium iodide) or changes in the pH of the medium. These results give further support to the antioxidant effect of N-acetylcysteine in human peripheral blood cells.

Acetylcysteine↗

Autotransplantation of peripheral blood stem cells mobilized by G-CSF in hematological malignancies: evidence for rapid and long-term sustained hematopoietic reconstitution.

We assessed the ability of granulocyte colony-stimulating factor (G-CSF) to mobilize peripheral blood stem cells (PBSC), the efficacy of PBSC infusion in the rescue of hematopoiesis after high-dose chemotherapy in 22 adult patients with hematological malignancies, and the long-term quality of engraftment. Bolus subcutaneous injections of G-CSF (12 micrograms/kg/day) were administered for 6 days. A median of three leukaphereses resulted in the collection of a median of 5.45 X 10(8) mononuclear cells/kg, 4.52 X 10(6) CD34+ cells/kg, and 3.97 X 10(4) CFU-GM/kg. G-CSF (5 micrograms/kg daily) was administered after PBSC infusion until granulocyte recovery. The median time to attain a neutrophil level > 0.5 X 10(9)/L and a platelet count > 20 X 10(9)/ L was 11 days. The median follow-up in 17 survivors was 23.8 months. These patients have maintained a complete and stable graft and some of them with neoplastic recurrence tolerated further chemotherapy. These results confirm that mobilization of PBSC by G-CSF can be performed on an outpatient setting and used in heavily pretreated patients. G-CSF mobilized PBSC transplantation provides early and complete engraftment in most patients.

Adult↗

Clinical implications of natural killer (NK) cytotoxicity in patients with squamous cell carcinoma of the uterine cervix.

Natural killer (NK) activity in peripheral blood mononuclear cells (PBMC) from women with squamous cell carcinoma of the uterine cervix (SCCUC) was studied. PBMC were obtained from 26 previously untreated patients with SCCUC at different stages of disease according to the FIGO classification (5 at stage I, 4 at stage II, 5 at stage III, 6 at stage IVa, and 6 belonging to stage IVb), as well as from 23 healthy age-matched women. These cells were used as effectors against 51Cr-labeled K-562 target cells in standard 4-hr cytotoxic assays. The NK activity displayed by PBMC from patients with local stages of the neoplasm (I, II, III, and IVa) was found to be similar to that exerted by PBMC from healthy controls (P greater than 0.05). Furthermore, there were no significant differences among mean values of NK activity in PBMC from women at these different stages of the disease (P greater than 0.05). However, the NK activity detected in the PBMC of patients with distant metastatic spread of the disease (stage IVb) was significantly depressed with respect to both controls and patients at any other earlier stage (P less than 0.05). We conclude that a decrease in the NK activity present in PBMC from women with SCCUC coincides with distant tumoral dissemination of the disease.

Carcinoma, Squamous Cell↗

Proliferation of B cells from chronic lymphocytic leukemia is selectively promoted by B cell growth factor.

B cell activation was studied in B cells from B cell chronic lymphocytic leukemia (B-CLL) patients. After in vitro stimulation, these B cells showed extensive proliferation in the presence of high-molecular-weight B cell growth factor (BCGF). In contrast, this effect was not observed upon addition of recombinant interleukin-2 (IL-2). In agreement, upon stimulation, B cells expressed Bac-1 antigen but failed to acquire the IL-2 receptor. These results demonstrate that the utilization of the BCGF pathway can be segregated from that of IL-2 in B cells from B-CLL patients.

B-Lymphocytes↗

Diminished natural killer activity in pregnancy: modulation by interleukin 2 and interferon gamma.

We investigated the alterations of natural killer (NK) cells in pregnancy, which led to decreased killing from the first trimester to the puerperium. We show that this phenomenon cannot be ascribed to a defective number of NK cells since the amounts of HNK-1+, CD16+ (Leu 11), and CD11b+ (OKM1) cells were within normal ranges. Recombinant interleukin 2 (rIL-2) corrects the functional defect in a dose and time-dependent manner, without modification in the surface phenotype of the population. Analysis of the pattern of target cell susceptibility to lysis, together with the similar ability of recombinant interferon gamma (rIFN-gamma) to correct the deficiency, and CD16+, CD3- phenotype of the precursor and effector lymphocytes, demonstrated that the induced cytotoxicity was mediated by NK cells. Inhibitors in pregnancy sera block IL-2 production by specific T cells, but we show that they do not influence either NK activity or its reconstitution by rIL-2. These findings place the deficiency at the level of NK cell maturation into cytotoxic effector lymphocytes. Thus, homeostasis of the NK activity of pregnant women may provide a biological model for clarifying the internal mechanisms regulating NK-cell activation in vivo. Present studies in vitro suggest that modulation of lymphokine production may play a role in the adaptive response of NK cells in pregnancy.

Cell Differentiation↗

Clinical signification of natural killer activity in B-cell chronic lymphocytic leukemia.

The natural killer (NK) activity of peripheral blood mononuclear cells (PBMC) and lymphocytes with the capacity to form stable rosettes with neuraminidase-treated sheep red blood cells (E+) was studied in 28 previously untreated patients (11 at stage 0, 10 at stage I and 7 at stages II and III, according to Rai's classification) and 7 treated patients with B-cell chronic lymphocytic leukemia (B-CLL), all of them at stage 0 according to Rai's classification after treatment, and in 15 healthy controls. The mean NK activities of PBMC and E+ lymphocytes from untreated patients were significantly decreased (p less than 0.001) when compared with those of PBMC and E+ lymphocytes, respectively, from healthy controls. However, PBMC and E+ cells from treated patients demonstrated NK activity similar to that of the corresponding cellular populations of controls (p greater than 0.05). Furthermore, there were no significant differences among the NK activities of E+ lymphocytes from untreated B-CLL patients in the different clinical stages 0, I, II and III, according to Rai's classification (p less than 0.05). These results demonstrate that the very low or undetectable levels of NK activity present in PBMC and E+ cell populations from previously untreated patients with B-CLL, regardless of the clinical stage of the disease, can be modified by systemic therapy with alkylating agents. Moreover, the NK activity of PBMC and E+ lymphocytes from some treated patients that have achieved the stage 0 according to Rai's classification after chemotherapy can be found within the range of the lytic activity shown by PBMC and E+ cells from normal donors.

Animals↗