Cell Reprogramming, IPS Limitations, and Overcoming Strategies in Dental Bioengineering.

The procurement of induced pluripotent stem cells, or IPS cells, from adult differentiated animal cells has the potential to revolutionize future medicine, where reprogrammed IPS cells may be used to repair disease-affected tissues on demand. The potential of IPS cell technology is tremendous, but it will be essential to improve the methodologies for IPS cell generation and to precisely evaluate each clone and subclone of IPS cells for their safety and efficacy. Additionally, the current state of knowledge on IPS cells advises that research on their regenerative properties is carried out in appropriate tissue and organ systems that permit a safe assessment of the long-term behavior of these reprogrammed cells.

Stem cell and regenerative medicine.

Stem cells have been identified and isolated in many adult tissues. They exhibit a great plasticity and the ability to give rise to differentiated cells of several lineages. The possibility of transplantation of these stem cells into an adult to develop, integrate and rebuild destroyed tissues or organs has encouraged the study of the mechanisms of the differentiation of stem cells.

Effect of IL-2 and IL-6 on parameters related to metastatic activity in a murine melanoma.

Previous results have shown that the metastatic colonization with B16F10 melanoma in vivo increased after in vitro treatment of the cells with IL-2 or IL-6. To further investigate the mechanisms underlying this effect, we have studied adhesion, invasion, and proliferation properties of B16 melanoma, using two sublines with different metastatic ability. Adhesion of tumor cells to Matrigel coats increased using IL-6, which also induced upregulation of VLA-4 expression in both sublines.

Interleukin-2 enhances the growth of human melanoma cells derived form primary but not from metastatic tumours.

Previously, we demonstrated that in vitro treatment of B16F10 murine melanoma cells with interleukin-2 (IL-2) enhances proliferation and metastasis. To further investigate the role played by IL-2 in human melanomas, we studied the expression of IL-2/IL-2 receptor and the effect of IL-2 on the proliferation of melanoma cell lines derived from primary (A375 and RMS cell lines) and metastatic (Hs294T cell line) tumours. We found a constitutive expression of cytoplasmic IL-2 and alpha, beta and gamma-subunits of the IL-2R on the surface of the three melanoma cell lines.

Soluble interleukin-2 receptor, intercellular adhesion molecule-1 and interleukin-10 serum levels in patients with melanoma.

Serum soluble interleukin-2 receptor (sIL-2R), intercellular adhesion molecule-1 (sICAM-1) and interleukin-10 (IL-10) have each been reported as useful markers for melanoma progression. To evaluate the clinical relevance of these three markers, we simultaneously analysed their serum levels in patients with melanoma. A longitudinal study with a 3-year follow-up was performed and different stages of the disease were considered.

[Acute myeloid leukemia in those over 70 years of age. Experience using low-dose ara-C treatment].

Purpose: The treatment of elderly patients with acute myeloid leukaemia (AML) remains controversial. We present the results of the treatment of a group of patients aged above 70 years with AML diagnosed in our Hospital since 1990.

Patients And Methods: We have studied retrospectively the cases of AML in patients older than 70 years diagnosed in our Service since January 1990 to June 1996.

Serum-soluble IL-2 receptor and IL-6 levels in patients with melanoma.

Elevated soluble IL-2 receptor (sIL-2R) and IL-6 serum concentrations have been reported as adverse prognostic factors in several types of cancer. In order to determine whether these factors are predictive of metastatic progression in melanoma, sIL-2R and IL-6 levels were measured in sera from 172 patients with melanoma and 60 in healthy controls. Mean sIL-2R values were significantly higher in the patients than in normal controls and the highest values were observed in those that developed metastasis during follow-up.

IL-2 treatment of B16F10 melanoma cells stimulates metastatic colonization in the liver.

We had previously shown that murine B16F10 melanoma cells express the receptor for IL-2, transcribe the gene for IL-2 and respond to its factor by increasing their proliferation. In the present work we have investigated the effect of in vitro IL-2 treatment on the metastatic ability of B16F10 cells. In vivo experiments showed that the metastatic colonization of the liver was notably higher after intrasplenic inoculation of IL-2-treated cells.

[Comparative study of the stability of oral anticoagulant treatments (warfarin vs acenocoumarol)].

Purpose: To compare the stability of the effect of two oral anticoagulants, one of them (acenocoumarol) with a short half life and the other one with a long half life (warfarin) in patients in the stable phase of treatment (at least 2 months with treatment before entering the study).

Patients And Methods: During a year period (January-December 1993) a comparative study of two groups of 53 patients each was performed: group 1 patients were treated with warfarin and group 2 with acenocoumarol. Both groups were paired with respect to age, sex, diagnosis for anticoagulant therapy and desired therapeutic range (INR 3-4.

B16F10 murine melanoma cells express interleukin-2 and a functional interleukin-2 receptor.

In this study, we analyzed interleukin-2 (IL-2) and IL-2 receptor (IL-2R) expression in murine B16F10 melanoma and studied the effect of recombinant IL-2 (rIL-2) on the proliferation of these cells. Flow cytometry analysis revealed the presence of the IL-2R alpha subunit in B16F10 melanoma, with a mean positivity rate of 30%. Using confocal microscopy, the expression of this chain could be visualized on the surface of B16F10 cells and in intracellular compartments when the cells were permeabilized with ethanol.

A laboratory model of canine leishmaniasis: the inoculation of dogs with Leishmania infantum promastigotes from midguts of experimentally infected phlebotomine sandflies.

Twenty-five dogs (beagles) were infected with Leishmania infantum by the intradermal inoculation of an estimated 5-8,000 metacyclic promastigotes harvested from the midguts of 320 experimentally infected P. perniciosus. Details are given of the methods of infecting the flies and harvesting the parasites.

[Human recombinant erythropoietin in the treatment of myelodysplastic syndromes anemia. Meta-analytic study].

Purpose: To study the usefulness of different published epidemiological and analytic parameters to decide the treatment with human recombinant erythropoietin (rHuEPO) of anaemic patients with myelodysplastic syndromes (MDS).

Patients And Methods: We have revised 10 published series compiling 115 patients, studying age, sex, initial diagnosis, route of administration and posology, criteria of response, duration of the study, dosis with the response was obtained, response according to initial diagnosis, duration of responses, and effect of the treatment on other hematopoietic series. We have made a comparison between responders and non-responders based on epidemiological and analytical parameters.

[Treatment with oral anticoagulants (acenocoumarol): influence of the initial doses in the incidence of hemorrhagic and thromboembolic episodes].

Purpose: To compare two initial doses of oral anticoagulant (acenocoumarin) studying the haemorrhagic and thromboembolic episodes occurred during the first month of treatment, the mean time and necessary controls until achievement of the desired level of anticoagulation.

Patients And Methods: From january 1992 to december 1993; a comparative study of two groups of patients was performed: group 1, compiling 129 patients chosen at random and retrospectively, who begun oral anticoagulant treatment with 4 daily mg of acenocoumarin; and group 2, compiling 129 patients chosen prospectively, who begun with 2 mg daily. In both groups the mean time and the number of controls performed until achieving the desired level of anticoagulation were analyzed, as well as the haemorrhagic episodes occurred during the first month of treatment, their severity (classified into major and minor ones), the level of anticoagulation when they occurred and their possible causes.

[Lymphoma of the ocular adnexa].

Ocular adnexa are rarely involved in lymphomas. Four cases are reported of lymphoma involving the ocular adnexa. In two cases a previous systemic involvement existed or simultaneous to the ocular involvement; another patient had systemically a different histological pattern to that observed in the ocular region, and the fourth patient only had ocular region, and the fourth patient only had ocular symptoms; we therefore recorded two cases of primary ocular lymphoma.

Enhancement of Ia antigen expression and nonproliferating cells correlates with metastatic capacity.

Maintaining B16F10 tumor cells in stirring culture for 48 h leads to an increase in lung and liver colonizing capacity in comparison with cells in adherent culture. Parallel to the increased metastatic capacity, we have observed a decrease in the proliferative rate of tumor cells (as the percentage of proliferating cell nuclear antigen-positive cells) and an increase in the population of tumor cells expressing Ia antigen. These results are not exclusive to B16F10 cells, since the same results were obtained when we analyzed 3LL cells maintained in identical culture conditions.

[Hemorrhagic complications in patients treated with oral anticoagulants].

Purpose: We have studied the haemorrhagic episodes occurred in patients treated with oral anticoagulants, with special reference to their type, frequency and severity and analyzing the risk factors that could influence in their production.

Patients And Methods: We carried out a retrospective study in 435 patients of the haemorrhagic episodes occurred since January 1989 to December 1991, determining in each one the prothrombin time expressed as INR, the time from the beginning of treatment, the patient's age and the known or underlying pathologies that could predispose to haemorrhage; depending on their severity these episodes were classified as moderate and major.

Results: We observed 50 haemorrhagic episodes in 50 patients (11.

[Chronic neutrophilic leukemia associated with myeloma. Simultaneous presentation].

A case of chronic neutrophilic leukaemia associated with multiple myeloma is reported. The patient had a 6 months history of bruising and weight loss, and showed mature neutrophilic leukocytosis, hepatosplenomegaly, high neutrophil alkaline phosphatase score, hyperuricaemia, neutrophils with pseudotoxic granulation and scarce Döhle bodies; moreover, a monoclonal IgG lambda was detected amounting 57.3 g/L.

Epidemiology of canine leishmaniasis: prevalence, incidence and basic reproduction number calculated from a cross-sectional serological survey on the island of Gozo, Malta.

Assessment of the resilience of canine leishmaniasis to control or, more ambitiously, the effort needed to eradicate infection, requires an estimate of the basic case reproduction number (R0). This paper applies the theoretical results of Hasibeder, Dye & Carpenter (1992) to data from a cross-sectional survey on the Maltese island of Gozo in which dogs of known age, sex and occupation (pet, guard etc) were subjected to three different serological tests for the presence of specific antibody (IFAT, DAT and ELISA). Difficulties in interpreting these test results, and hence of determining the proportion of dogs infected, present the main obstacle to estimating R0: estimates are critically dependent on the choice of threshold separating seropositives from seronegatives.

Kinetics and regulation of NK activity by interleukin-2 and interferon in acute toxoplasmosis.

Natural killer (NK) activity against Toxoplasma gondii tachyzoites and tumour cells during acute toxoplasmosis was investigated using a single-cell NK assay. During the course of infection the percentage of lymphocytes binding tachyzoites and tumour cells did not vary significantly and NK activity was enhanced due to an increase in the specific cytolytic capacity per cell. To determine whether regulatory mechanisms mediated by cytokines might explain the increased NK activity, the kinetics of interleukin-2 (IL-2) and interferon (IFN) production and the correlation between their concentrations and the level of NK activity were analysed at the same time.

MHC class I antigen expression and alterations induced by rIFN gamma in tumor hybrid cell immunogenicity.

Hybridization of a poorly immunogenic tumor cell with an allogeneic cell was performed in order to improve tumor immune response; several variants derived from one hybrid tumor cell were studied. We compared the immunogenicity of these variants and their allogeneic and syngeneic class I antigen expression before and after IFN gamma treatment. Allogeneic class I antigens were weakly expressed in all variants; IFN treatment enhanced their expression similarly in both immunogenic and nonimmunogenic variants.

[Effect of treatment with clindamycin, erythromycin, rifamycin or gentamicin on the ingestion capacity of peritoneal macrophages in mice].

The effect of treatment with clindamycin, erythromycin, rifamycin and gentamicin on the ingestion capacity of the mouse peritoneal macrophage was studied. Female six-eight week old OF1 mice were treated with minimum and maximum doses clinically used for the different antibiotics (15 and 40 mg/kg/day of clindamycin, 15 and 57.5 mg/kg/day of erythromycin, 10 and 30 mg/kg/day of rifamycin, 3 and 6 mg/kg/day of gentamicin).

Are laminin binding sites on tumor cell surface involved in the indomethacin-induced sensitivity to natural cytotoxic cells?

Prostaglandins are secreted by a variety of tumor cell lines. The prostaglandin synthesis inhibitor indomethacin (IND) inhibits 3LL tumor growth after both intramuscular or intrasplenic transplantation (45 and 72%, respectively). Moreover, when tumor cells were cultured with IND, the sensitivity of 3LL cells to natural cytotoxic (NC) effector cells was increased (30%) and a higher cytotoxicity was reached when both target and effector cells were treated.