Biomedical subjects

C Soler

Publications and source records attributed to C Soler.

At least 37 records · Page 2Linked to original sources

PubMed2000

The expression of MHC class II genes in macrophages is cell cycle dependent.

Using different drugs, we stopped the cell cycle of bone marrow-derived macrophages at different points. After IFN-gamma stimulation, macrophages arrested at the G(1) phase of the cell cycle did not increase cell surface expression of the MHC class II IA. This inhibition is specific, because, under the same conditions, IFN-gamma induces the expression of Fcgamma receptors and the inducible NO synthase mRNA. Treatments that inhibit macrophage proliferation by blocking the cell cycle at the G(1) phase, such as adenosine, forskolin, or LPS, blocked the IFN-gamma induction of IA. Under IFN-gamma treatment, the steady-state levels of IAalpha and IAss mRNA did not increase in cells arrested at the G(1) phase and the half-life of the MHC mRNA was not modified. These data suggest that the cell cycle modulation of IFN-gamma-induced MHC II gene expression occurs at the transcriptional level. The expression of the class II transactivator mRNA induced by IFN-gamma was also blocked when macrophages were arrested at the G(1) phase of the cell cycle, suggesting that the lack of IFN-gamma response occurs at the early steps of MHC class II expression. Finally, macrophages arrested at the G(1) phase showed increased basal levels of cell surface IA due to an increase of the translational efficiency. These data show that the expression of MHC class II genes is regulated by the cell cycle.

Animals↗

PubMed2000

nef/long terminal repeat quasispecies from HIV type 1-infected Mexican patients with different progression patterns and their pathogenesis in hu-PBL-SCID mice.

To examine the genetic features of the long terminal repeat (LTR) derived from six HIV-1-infected individuals enrolled in the Mexico City Cohort, we cloned and sequenced a 505-bp fragment of the proviral LTR from their peripheral blood mononuclear cells (PBMCs). All patients harbored HIV-1 LTR quasispecies corresponding to the B subtype. Three patients with high CD4+ T cell counts (>500/mm3) presented LTR sequences with point mutations in the TAR bulge. The LTR sequence from a patient classified as a long-term nonprogressor (LTNP) presented the most frequent naturally occurring length polymorphism (MFNLP) and two substitutions in the TAR region that were predicted to result in two alternative secondary RNA structures. A novel 18-bp deletion, which eliminates part of the putative binding site for the nuclear factor of activated T cells (NFAT-1), was identified in the overlapping nef/LTR sequence derived from a patient progressing to AIDS. This deletion coincides with the ability of this virus to consistently replicate at low levels in vivo (viral load <500 RNA copies/ml) and in vitro (unsuccessful virus isolation). On one occasion, when virus isolation was successful, the 18-bp deletion was no longer evident and LTR sequences with intact NFAT-1-binding sites were observed. Inoculation of hu-PBL-SCID mice with viruses from several Mexican patients resulted in differential CD4+ T cell depletion patterns 15 days postinfection, which agree with the in vivo CD4+ T cell count data from each patient.

Acquired Immunodeficiency Syndrome↗

PubMed2000

Protein kinase C epsilon is required for the induction of mitogen-activated protein kinase phosphatase-1 in lipopolysaccharide-stimulated macrophages.

LPS induces in bone marrow macrophages the transient expression of mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1). Because MKP-1 plays a crucial role in the attenuation of different MAPK cascades, we were interested in the characterization of the signaling mechanisms involved in the control of MKP-1 expression in LPS-stimulated macrophages. The induction of MKP-1 was blocked by genistein, a tyrosine kinase inhibitor, and by two different protein kinase C (PKC) inhibitors (GF109203X and calphostin C). We had previously shown that bone marrow macrophages express the isoforms PKC beta I, epsilon, and zeta. Of all these, only PKC beta I and epsilon are inhibited by GF109203X. The following arguments suggest that PKC epsilon is required selectively for the induction of MKP-1 by LPS. First, in macrophages exposed to prolonged treatment with PMA, MKP-1 induction by LPS correlates with the levels of expression of PKC epsilon but not with that of PKC beta I. Second, Gö6976, an inhibitor selective for conventional PKCs, including PKC beta I, does not alter MKP-1 induction by LPS. Last, antisense oligonucleotides that block the expression of PKC epsilon, but not those selective for PKC beta I or PKC zeta, inhibit MKP-1 induction and lead to an increase of extracellular-signal regulated kinase activity during the macrophage response to LPS. Finally, in macrophages stimulated with LPS we observed significant activation of PKC epsilon. In conclusion, our results demonstrate an important role for PKC epsilon in the induction of MKP-1 and the subsequent negative control of MAPK activity in macrophages.

Bone Marrow Cells↗

PubMed2000

Effect of cetrorelix on sperm morphology during migration through the epididymis in the cynomolgus macaque (Macaca fascicularis).

The importance of the cynomolgus monkey as a model for human reproductive medicine prompted this examination of epididymal sperm morphology. Computer-aided sperm morphological analysis was used for the first time to provide morphometric data on sperm heads as they traversed the epididymal duct of Macaca fascicularis. The duct was divided into six regions, starting close to the testis (proximal) and ending close to the vas deferens (distal). To determine the androgen-dependence of the changes, one group of animals received a GnRH-antagonist (Cetrorelix, Asta Medica, Frankfurt, Germany) to induce testicular regression and lower epididymal androgens, while a control group received only vehicle. Epididymides were removed 16 and 25 days after treatment, and sperm heads were analysed by a computer-assisted morphometric analyser. Cluster analysis revealed swollen sperm head cells in proximal regions 1 and 2 of the epididymis, but fewer such forms distally. Normal head shapes became the majority in region 4 and these underwent a gradual but statistically significant decrease in size (area, perimeter, length, width) and shape as they reached the distal regions. In the animals given Cetrorelix, sperm with swollen heads were found more distally than in the controls, although they were also never present in the distal cauda (region 6). Normal heads still became predominant in region 4 after 16 days treatment, and in region 6 after 25 days. The normal forms in the cauda epididymidis of treated animals were significantly larger than cells from control animals. We conclude that epididymal sperm maturation in the monkey is characterised by both a loss of sensitivity to distortion on air-drying, and by a decrease in sperm head size. The former, but not the latter, is attained by sperm in androgen-deficient epididymides from GnRH-antagonist-treated monkeys.

Animals↗

PubMed2000

Nitric oxide regulates nucleoside transport in activated B lymphocytes.

Activation of human B lymphocytes by lipopolysaccharide (LPS) or phorbol 12-myristate 13-acetate (PMA) results in the differential regulation of nucleoside uptake [Soler, C., Felipe, A., Mata, J. F., Casado, F. J., Celada, A., Pastor-Anglada, M. (1998) J. Biol. Chem. 273, 26939-26945]. Because nitric oxide (NO) is involved in the modulation of the apoptotic response of B cells, the effects of NO on the regulatory responses of these transport systems to phorbol esters has been studied in Raji cells by a combination of approaches that involve arginine depletion, inhibition of nitric oxide synthase, and non-enzymatic production of NO using a donor. Human B lymphocytes express three transport systems involved in nucleoside uptake: N1 and N5, which are concentrative and Na+-dependent, and the nitrobenzylthioinosine-sensitive equilibrative system es. Raji cells do not express significant amounts of iNOS mRNA or protein; thus, NO production is presumably constitutive. The data are consistent with a role of NO in maintaining the basal transport activities of the three systems: N1, N5, and es. However, the up-regulatory effect of PMA on N1 and N5 does not require NO, whereas the inhibition of es transport activity does. In summary, NO differentially modulates nucleoside transport systems in activated human B lymphocytes and thus, NO may also be involved in the regulation of nucleoside (i.e., adenosine) disposal by activated B cells.

Arginine↗

PubMed2000

Nephrogenic adenofibroma in a young child.

Nephrogenic adenofibroma is a benign renal tumor in children and young adults described by Hennigar and Beckwith in 1992. Seven cases have been described, and we report the first case in an 11-month-old child, in good health, revealed by a macroscopic hematuria. Nephrogenic adenofibroma is an unusual tumor, which was difficult to distinguish from nephroblastoma and mesoblastic nephroma. Beckwith makes a distinction between this principal differential diagnosis in child renal tumors based upon morphologic and immunohistochemical patterns. In our observation, the diagnosis remained difficult and needed several reviews of our case. Beckwith proposed the final diagnosis: nephrogenic adenofibroma with stromal predominance. The prognosis is excellent and no treatment is indicated. A FISH analysis of the tumor cells found a trisomy 11. Trisomy 11 has been reported in mesoblastic nephroma as the most frequent chromosomal abnormality. This finding in tumor cells provides an argument for excluding the diagnosis of nephroblastoma but can not clarify the difference between nephrogenic adenofibroma and mesoblastic nephroma.

Adenofibroma↗

PubMed2000

Quantitative assessment of gait deviation: contribution to the objective measurement of disability.

Three biomechanical parameters based on force plate measurements were defined as indicators of gait deviation. Symmetry was specified as the relative difference in stance time and vertical impulse loading between both feet, constancy as the mean S.D. of the force curves for one subject under a specified gait condition and discrepancy as the average difference between the individual gait pattern and the expected force curves, normalised by the value of the S.D. in a control group. One hundred and forty four patients with osteoarthritis (OA) of the lower extremity and 144 control subjects were studied. There were 45 patients with OA of the hip, 54 of the knee and 45 of the ankle and their function was determined using the Harris Hip score, the hospital for special surgery knee score and the Mazur ankle score, respectively. The temporal asymmetry indicator was more sensitive to unilateral joint affliction, whereas the discrepancy indicators were sensitive to the presence of OA. Both correlated with the patient's function as measured by the relevant clinical score. A significant increase of gait discrepancy was detected in the arthritis group when patients were asked to walk at faster speeds; whilst walking barefoot led to an unexpected reduction of intra-subject kinetic variability. Our results confirm the validity and usefulness of the gait deviation concept in patients with OA.

Adolescent↗

PubMed2000

Objective evaluation of the morphology of human epididymal sperm heads.

Spermatozoa were obtained from nine epididymal regions of six epididymides taken from five men undergoing castration for prostatic carcinoma (53-76 years) and from one man with testicular cancer (38 years). Spermatozoa were obtained by mincing tissue in phosphate-buffered saline, making air dried smears and staining with Hemacolor. The percentage of sperm heads categorised subjectively as normal (of uniform shape) or otherwise was calculated for each region. This confirmed that grossly swollen sperm heads (previously shown to be artefacts) were only present in proximal regions of the duct. A computer-aided sperm morphology analyser (Sperm Class Analyzer(R)) was used to provide objective measurements of sperm head area, perimeter, length and width of the uniform sperm heads and revealed that there was a gradual and statistically significant decline in sperm head size upon maturation, as occurs in other species. There was no significant difference between the morphometric parameters of spermatozoa obtained from the distal cauda epididymis and those obtained from the ejaculates of young normozoospermic patients.

Adult↗

PubMed2000

Comparative study of sequential combinations of paclitaxel and methotrexate on a human bladder cancer cell line.

We investigated the cytotoxic effect of different sequential combinations of paclitaxel (Taxol, TX), an antimicrotuble agent, and methotrexate (MTX), a potent inhibitor of dihydrofolate reductase, on a human bladder cancer cell line (T24). The results obtained with a colony-forming assay 5 days after 24 hr of exposure to TX alone showed a strong decline in colony growth up to a concentration of 6 nM. There was a plateau phase at TX concentrations ranging from 6 to 10 nM. The IC50 values found with the different dosing sequences and 24-hr exposure to the drugs were 0.24 microM for MTX alone, 3.49 nM for TX alone, 3.84 nM for TX followed by MTX, 3.75 nM for TX and MTX simultaneously, and 2.10 nM for MTX followed by TX. The cytotoxic effect due to drug interactions in the different sequential combinations was evaluated by an algebraic method. All the combination sequences were found to be synergistic (combination index [CI] < 1) at low TX concentrations. An antagonistic effect (CI > 1) was obtained at higher TX concentrations. Our data demonstrate that the T24 cell line is sensitive to TX and that the cytotoxic effect is enhanced to different degrees depending on the treatment sequence when TX is combined with MTX. These findings could have implications in the design of appropriate administration schedules of these two drugs for the treatment of bladder cancer.

Antimetabolites, Antineoplastic↗

PubMed2000

Diffuse vertebral body metastasis from a glioblastoma multiforme: a technetium-99m Sestamibi single-photon emission computerized tomography study.

The authors report on a case of right temporal glioblastoma multiforme (GBM) that metastasized to multiple bone regions (dorsolumbar vertebrae and iliac bone) 8 months after initial diagnosis, despite combined radio- and chemotherapy. Results of a whole-bone single-photon emission computerized tomography (SPECT) study using the imaging agent Sestamibi (MIBI) revealed extracranial metastases from the GBM. A magnetic resonance imaging study of the dorsolumbar spinal region completed the radiological investigation. Cells immunoreactive to glial fibrillary acidic protein were observed in a specimen obtained from the right iliac bone. Postmortem examination confirmed metastasis to extracranial bone and revealed two other metastatic localizations in the lung and heart. This is the first reported case of extracranial bone metastasis from a GBM demonstrated on a whole-bone MIBI SPECT scan. In patients with malignant glioma and lower-back pain (especially prolonged pain), bone metastasis, although uncommon, does occasionally occur and its possibility should be investigated; a MIBI SPECT study may prove useful in this regard.

Bone Neoplasms↗

PubMed2000

Development of mouse testis and epididymis following intrauterine exposure to a static magnetic field.

In order to test if the in utero exposure to static magnetic fields affects testis and epididymis development in mice, females were exposed to 0.5-0.7 T, generated by a permanent magnet, from day 7 of gestation to the day of birth. No significant differences were found between exposed and sham-exposed animals with respect to body weight gain of dam during the gestational period, litter size, body weight of male pups at the day of birth, and body or testis-epididymis weight gain of pups from birth to day 35. Histopathologic evaluation of testis and epididymis of pups of 1, 5, 15, and 35 days of age showed no detectable alterations due to in utero exposure to static magnetic fields.

Aging↗

PubMed2000

[Solid and pseudopapillary tumor of the pancreas: immunohistochemical and ultrastructural study of 2 pediatric cases].

We report 2 cases of solid and pseudopapillary tumors of the pancreas occurring in female children. Lesions were made of uniform small cells arranged in solid areas associated with pseudopapillary and cystic patterns. Immunohistochemistry study was positive for neuron-specific enolase, alpha-1 anti-trypsin and vimentin. Ultrastructural study showed an abundant cytoplasm, rich in mitochondria, containing a lot of granules of variable sizes, often disintegrated, and some lipid droplets. The differential diagnosis of this lesion included endocrine tumor, pancreatoblastoma and acinar cell carcinoma. It is a rare tumor of the pancreas with a favorable prognosis after complete resection.

Adolescent↗

PubMed2000

[Detection of lymphatic metastasis from malignant melanoma after identification of the sentinel node by preoperative lymphoscintigraphy and intraoperative radioisotopic detection].

OBJECTIVES: The aim of this study was to evaluate the detection of the first lymph node draining the primary tumour site, using a radioisotopic mapping alone and to determine whether a preoperative lymphoscintigraphy using technetium sulfur colloid and a hand-held gamma detecting probe could improve the detection of the sentinel lymph node (SLN) in melanoma. PATIENTS AND METHOD: From January to December 1998, 36 patients with a cutaneous melanoma larger than 0.75 mm, stage I TNM were included in this prospective study. Mean Breslow was 1.85 mm. The distribution of melanoma was head and neck (n = 9), trunk (n = 7), upper extremities (n = 4), lower extremities (n = 16). Preoperative lymphoscintigram and intraoperative detection were used. The first hot lymph node was supposed to be the SLN. RESULTS: In all cases, a lymph node was found and nine patients had more than one SLN (average number of SLN per patient: 1.25). Aberrant drainages were found in seven patients (19.4%): 1 in-transit lymph node, three paradoxical bassins, three bypasses). Four out of 36 patients had lymph node metastases and underwent elective lymph node dissection. CONCLUSION: The radio-isotopic technique used alone for the identification of the SLN is efficient in melanoma with a 100% detection rate in this short series.

Adult↗

PubMed2000

[Cutaneous nodular infection with hemopathy].

A 36-year-old man with treated hairy cell leukemia developed a skin infection due to Mycobacterium marinum. A spectrum of atypical cutaneous mycobacteriosis presentations with immunosuppression can be found. The recognition of the disease needs cutaneous biopsies for histopathology and its identification by specific laboratory methods to adapt treatment.

Adult↗

PubMed1999

IFN-gamma up-regulates the A2B adenosine receptor expression in macrophages: a mechanism of macrophage deactivation.

Adenosine is a potent endogenous anti-inflammatory agent released by cells in metabolically unfavorable conditions, such as hypoxia or ischemia. Adenosine modulates different functional activities in macrophages. Some of these activities are believed to be induced through the uptake of adenosine into the macrophages, while others are due to the interaction with specific cell surface receptors. In murine bone marrow-derived macrophages, the use of different radioligands for adenosine receptors suggests the presence of A2B and A3 adenosine receptor subtypes. The presence of A2B receptors was confirmed by flow cytometry using specific Abs. The A2B receptor is functional in murine macrophages, as indicated by the fact that agonists of A2B receptors, but not agonists for A1, A2A, or A3, lead to an increase in cAMP levels. IFN-gamma up-regulates the surface protein and gene expression of the A2B adenosine receptor by induction of de novo synthesis. The up-regulation of A2B receptors correlates with an increase in cAMP production in macrophages treated with adenosine receptor agonist. The stimulation of A2B receptors by adenosine or its analogues inhibits the IFN-gamma-induced expression of MHC class II genes and also the IFN-gamma-induced expression of nitric oxide synthase and of proinflammatory cytokines. Therefore, the up-regulation of the A2B adenosine receptor expression induced by IFN-gamma could be a feedback mechanism for macrophage deactivation.

Adenosine↗

PubMed1999

Dermal fibroblast proliferation is improved by beta-catenin overexpression and inhibited by E-cadherin expression.

Several recent studies have shown that proteins of the cadherin-catenin complex are not only involved in cell-cell adhesion but also in the proliferation and differentiation processes. For the first time, we investigated the effect of the quantity of cytoplasmic beta-catenin on dermal fibroblast proliferation by overexpressing human beta-catenin in human dermal fibroblasts. Our results show that dermal fibroblasts overexpressing normal beta-catenin or a stabilized beta-catenin mutant have a higher growth rate than control fibroblasts. Moreover, when confluence is reached, the number of fibroblasts is increased when the cells overexpress beta-catenin suggesting a role for beta-catenin in the regulation of contact growth arrest. Finally, by comparing proliferation in normal dermal fibroblasts and dermal fibroblasts expressing E-cadherin we observed a negative regulatory effect of E-cadherin expression on fibroblast proliferation. These data demonstrate the involvement of beta-catenin and cadherin in the dermal fibroblast proliferation process and in contact growth arrest.

Animals↗

PubMed1999

Morphological characterization of ejaculated cynomolgus monkey (Macaca fascicularis) sperm.

The aim of this study was to give reference values for the frequency of morphological sperm abnormalities present in the semen from non-experimental cynomolgus monkeys as well as for the dimensions of sperm heads. Spermatozoa from the liquid portion of electroejaculates from 14 cynomolgus monkeys were air-dried as smears, fixed, and stained with Harris's Haematoxylin and subjected to visual analysis of morphology and computer-aided analysis of ten morphometric variables. The majority (83%) of sperm were morphologically normal. Tail defects were the most common (11%), and showed the highest variation between individuals, the values ranging between 4 and 23%. Head abnormalities consisted of large, tapering, and amorphous forms but were not frequent (0.4%), the values ranging between 0 and 1.3%. Midpiece imperfections were found in all the individuals; the mean percentage was 5%, and the range varied between 3 and 9%. Tail plus midpiece was the only multiple abnormality observed, with a mean value of 1.5% and a range between 0 and 8%. The majority of these double defects consisted of a coiled tail together with a coiled midpiece. Mean values for the morphometric parameters characterizing sperm heads were as follows: area 17.2 microm2, perimeter 15.2 microm, length 5.8 microm, width 4.0 microm, L/W ratio 1.5, gray-level 98, ellipticity 0.2, first shape factor 0.9, second shape factor 1.4, and third shape factor 1.1. Overall coefficients of variation for the majority of parameters were below 7%, showing the great homogeneity in the dimensions of cynomolgus sperm heads. Most useful parameters for sperm characterization, according to their low variability, were perimeter, length, width, L/W ratio, and shape factors. Differences in these parameters were, however, observed between monkeys.

Animals↗

PubMed1999

Phase II study of a radiotherapy/etoposide combination for patients with newly malignant gliomas.

PURPOSE: Etoposide, a semisynthetic derivative of podophyllotoxine, is a topoisomerase II inhibitor. This drug is currently used in several types of human cancer. The aim of this study was to evaluate the efficacity and tolerance of a near-concurrent association of radiotherapy and etoposide for newly malignant gliomas. METHODS: From May 1995 to December 1996, 30 malignant glioma patients were included in this phase II study; 16 patients underwent surgical tumor resection, and a stereotactic biopsy was performed in 14 patients. Standard cranial irradiation and six courses of etoposide (100 mg/m2, x days 1-3) were administered. The first course of etoposide was administered on days 1-3 of radiotherapy and was resumed in the week following the end of radiotherapy. Treatment was consolidated by further courses of etoposide every 4 weeks. RESULTS: Only 26 patients could be evaluated for the purpose of our study. The median age was 60.1 years, and the median Karnofsky performance score (KPS) was 80.2. The rate of objective response for evaluable patients was 34.6%, and four complete responses (CR) and five partial responses (PR) were noted. The median survival (MST) was 12 months, and the average overall survival was 12.5 months. Hematological toxicity was mild, and grade 3 or 4 neutropenia (white blood cell count < 1500/ml) was noted in three patients, without any sepsis or bleeding. CONCLUSIONS: The results obtained in this study are comparable to the best reported results on the combination of radiotherapy and nitrosoureas. The near-concurrent combination of radiotherapy and etoposide seems to be effective and well tolerated in the treatment of newly malignant gliomas.

Adult↗