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Biomedical subjects

C Guillen

Publications and source records attributed to C Guillen.

At least 19 recordsLinked to original sources
PubMed2006

Differential mitogenic signaling in insulin receptor-deficient fetal pancreatic beta-cells.

Insulin receptor (IR) may play an essential role in the development of beta-cell mass in the mouse pancreas. To further define the function of this signaling system in beta-cell development, we generated IR-deficient beta-cell lines. Fetal pancreata were dissected from mice harboring a floxed allele of the insulin receptor (IRLoxP) and used to isolate islets. These islets were infected with a retrovirus to express simian virus 40 large T antigen, a strategy for establishing beta-cell lines (beta-IRLoxP). Subsequently, these cells were infected with adenovirus encoding cre recombinase to delete insulin receptor (beta-IR(-/-)). beta-Cells expressed insulin and Pdx-1 mRNA in response to glucose. In beta-IRLoxP beta-cells, p44/p42 MAPK and phosphatidylinositol 3 kinase pathways, mammalian target of rapamycin (mTOR), and p70S(6)K phosphorylation and beta-cell proliferation were stimulated in response to insulin. Wortmannin or PD98059 had no effect on insulin-mediated mTOR/p70S(6)K signaling and the corresponding mitogenic response. However, the presence of both inhibitors totally impaired these signaling pathways and mitogenesis in response to insulin. Rapamycin completely blocked insulin-activated mTOR/p70S(6)K signaling and mitogenesis. Interestingly, in beta-IR(-/-) beta-cells, glucose failed to stimulate phosphatidylinositol 3 kinase activity but induced p44/p42 MAPKs and mTOR/p70S(6)K phosphorylation and beta-cell mitogenesis. PD98059, but not wortmannin, inhibited glucose-induced mTOR/p70S(6)K signaling and mitogenesis in those cells. Finally, rapamycin blocked glucose-mediated mitogenesis of beta-IR(-/-) cells. In conclusion, independently of glucose, insulin can mediate mitogenesis in fetal pancreatic beta-cell lines. However, in the absence of the insulin receptor, glucose induces beta-cell mitogenesis.

Animals↗
PubMed2006

Basal cell carcinoma of the nasolabial fold: an apparently 'benign' tumour that often needs complex surgery.

BACKGROUND: Location of the tumour is a well-known prognostic factor for recurrence of basal cell carcinoma (BCC). We have observed that tumours located in the nasolabial fold may deserve a particular attention. OBJECTIVE: The aim of this study is to evaluate the behaviour of BCC located on the nasolabial fold in comparison to a control group of patients with BCC in lower risk sites, and to detect characteristics which may imply a more complicated treatment or the consideration of adjuvant treatment. METHODS: A series of 24 patients with BCC located on the nasolabial fold were retrospectively recruited from our database of Mohs surgery from January 1997 to December 2000. A control group of 37 patients with BCC located on the cheek or forehead were selected from the same database. The differences between both groups in clinical, surgical and histological terms were evaluated. RESULTS: BCC on the nasolabial fold presented with shorter evolution time from first symptom, had a smaller size, had been less frequently treated before and showed mostly non-aggressive histologic subtype, but needed more surgical stages and more complex reconstruction. CONCLUSION: We have observed that BCC on the nasolabial fold, despite presenting with better clinical and histological features, needed more complicated surgery. In our opinion, this location warrants a particular attention and further prospective studies should be made to corroborate our findings.

Aged↗
PubMed2005

Expression of CXCR6 and its ligand CXCL16 in the lung in health and disease.

BACKGROUND: Chemokine receptors (CR) play an important role in T cell migration, but their contribution to lung trafficking is unclear. OBJECTIVE: We hypothesized that if a particular CR was involved in T cell homing its expression would be enriched on lung T cells compared with peripheral blood T cells (PBT). METHODS: We have measured the CR expression on BAL T cells from patients with sarcoid, other interstitial lung diseases (ILD), asthma and healthy volunteers. RESULTS: Of 14 CR studied in sarcoid, CXCR6 expression was the most markedly increased in the lung compared with the blood, a finding that was also seen in ILD patients. A striking although lesser increase was also seen in asthmatics and healthy controls. Analysis of expression of the CXCR6 ligand, CXCL16, by immunohistochemistry suggested that alveolar macrophages (AM) were the major source of CXCL16 in the lung. AM expressed mRNA for CXCL16 and released nanogram quantities after adhesion to plastic as shown by RT-PCR, Western blotting and ELISA. Bronchoalveolar lavage (BAL) fluid from all subjects contained large amounts of CXCL16. The full-length CXCL16 was the predominant isoform in AM lysates, supernatants and BAL. CONCLUSION: This data suggests that CXCR6 and CXCL16 may play a role in T cell recruitment to the lung.

Adult↗
PubMed2003

Excellent response of basal cell carcinomas and pigmentary changes in xeroderma pigmentosum to imiquimod 5% cream.

Xeroderma pigmentosum (XP) is an autosomal recessive disease in which patients have a 1000-fold increased risk of developing cutaneous neoplasms. Management of patients with XP is a difficult therapeutic challenge as they usually present with many cutaneous malignancies and continue to form skin tumours at a high rate. We describe a 19-year-old woman with XP who had been previously treated with many different therapeutic approaches. She had an excellent clinical response of her multiple small pigmented basal cell carcinomas and pigmentary changes using imiquimod 5% cream with only minor side-effects.

Adult↗
PubMed2001

Liposomes as possible carriers for lactoferrin in the local treatment of inflammatory diseases.

Liposomes prepared from naturally occurring biodegradable and nontoxic lipids are good candidates for local delivery of therapeutic agents. Treatment of arthritis by intra-articular administration of anti-inflammatory drugs encapsulated in liposomes prolongs the residence time of the drug in the joint. We have previously shown that intra-articular injection of human lactoferrin (hLf), a glycoprotein that possesses anti-inflammatory and antimicrobial activities, into mice with collagen-induced arthritis reduces inflammation. We have now investigated the possibility of using liposome-entrapped hLf as a delivery system to prolong hLf retention at sites of local inflammation such as the rheumatoid joint. Entrapment of hLf in negatively charged liposomes enhanced its accumulation in cultured human synovial fibroblasts from rheumatoid arthritis (RA) patients, compared with positively charged formulations or free protein. However, in the presence of synovial fluid, positively charged liposomes with entrapped hLf were more stable than the negatively charged formulations. In vivo experiments in mice with collagen-induced arthritis showed that the positive liposomes were more efficient in prolonging the residence time of hLf in the inflamed joint as compared with other liposomes. Thus, the amount of hLf retained in the joint after 2 hr was 60% of the injected dose in the case of positive liposomes and only 16% for negative pH-sensitive liposomes. The results suggest that entrapment of hLf in positively charged liposomes may modify its pharmacodynamic profile and be of therapeutic benefit in the treatment of RA and other local inflammatory conditions.

Animals↗
PubMed2000

The effects of local administration of lactoferrin on inflammation in murine autoimmune and infectious arthritis.

OBJECTIVE: To determine whether lactoferrin can modify articular inflammation in murine models of autoimmune and septic arthritis. METHODS: Collagen arthritis was induced in DBA/1 mice and Staphylococcus aureus septic arthritis in Swiss mice. Joints with established inflammation were injected periarticularly with 0.5 mg or 1 mg of human lactoferrin, and arthritis was monitored for 3 days. RESULTS: DBA/1 mice injected with lactoferrin showed significantly suppressed local inflammation for up to 3 days, achieving up to 71% of the effect of corticosteroid. Periarticular injection of 125I-lactoferrin confirmed that 25% of lactoferrin was retained in paws after 6 hours. Serum levels of interleukin-6, however, were not significantly reduced, suggesting a predominantly local antiinflammatory effect. Similarly, local, periarticular administration of lactoferrin into S aureus-infected Swiss mice significantly suppressed paw inflammation and did not enhance bacterial survival. CONCLUSION: Lactoferrin may have clinical utility in reducing articular inflammation, particularly in septic arthritis, in which antiinflammatory effects may be achieved without promoting bacterial survival.

Administration, Topical↗
PubMed2000

Inherited palmoplantar keratoderma and sensorineural deafness associated with A7445G point mutation in the mitochondrial genome.

We report a French pedigree with members having an inherited combination of non-epidermolytic palmoplantar keratoderma (NEPPK) and sensorineural deafness. The penetrance of both features was incomplete. Additional ectodermal defects were absent. The expression of numerous epidermal proteins (keratins, fillagrin, cornified envelope proteins, intercellular junction proteins including connexin 26, and loricrin) defined with immunolabelling was normal in the proband. The combination was shown to be associated with the A7445G point mutation in the mitochondrial genome (mtDNA). This mutation is responsible for a subtype of NEPPK which is so far the only mtDNA mutation-associated keratoderma.

Adolescent↗
PubMed2000

Photodynamic therapy for in situ squamous cell carcinoma on chronic radiation dermatitis after photosensitization with 5-aminolaevulinic acid.

The accessibility of the skin to light treatment, as well as the developments made by dermatologists in photodynamic therapy (PDT), creates an exciting apportunity to include it as a part of our standard therapeutic armamentarium. We report a 63-year-old man with an in situ squamous cell carcinoma located on a chronic radiodermitis area in a finger, treated successfully with PDT. PDT appears to be a viable alternative to conventional therapy for in situ squamous cell carcinoma as well as for other superficial tumours of the skin.

Aminolevulinic Acid↗
PubMed1999

Parathyroid hormone-related protein (107-139) stimulates interleukin-6 expression in human osteoblastic cells.

The N-terminal region of both parathyroid hormone (PTH) and PTH-related protein (PTHrP) binds to the same PTH/PTHrP receptor in osteoblasts. However, C-terminal PTHrP (107-139) inhibits growth and various functions of osteoblasts and osteoclasts apparently through PTHrP-specific receptors. PTH (1-34) and PTHrP (1-34) rapidly induce interleukin-6 (IL-6) expression by osteoblasts. The aim of the present study was to assess the effects of PTHrP (107-139) on IL-6 gene expression and secretion by osteoblastic cells from human trabecular bone (hOB). Using reverse transcription followed by PCR, it was found that IL-6 mRNA was twofold maximally increased by either PTHrP (1-34) or PTHrP (107-139), at 10 nM, over basal within 1 to 2 h in hOB cells. This effect of PTHrP (107-139), and that of PTHrP (1-34), were abolished by the transcription inhibitor actinomycin D. Meanwhile, puromycin, a protein synthesis inhibitor, superinduced IL-6 expression in the presence or absence of each PTHrP peptide. Both PTHrP (1-34) and PTHrP (107-139), but not PTHrP (38-64), stimulated IL-6 secretion to the hOB cell-conditioned medium at 24 h, dose dependently. In addition, this maximal stimulatory effect (twofold over basal) was similar with each PTHrP peptide alone, and not additive when added together. PTHrP (107-139) stimulation of mRNA and protein in hOB cells was abolished by bisindolylmaleimide I, a protein kinase C inhibitor, but not by either adenosine 3',5'-cyclic monophosphorothioate, Rp-isomer (Rp-cAMPS), or N-[2-((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H89), two protein kinase A inhibitors. These results indicate that C-terminal PTHrP, like its N-terminal domain, induces IL-6 production by human osteoblastic cells. This effect of both PTHrP regions could provide a mechanism to modulate bone turnover.

Adult↗
PubMed1999

Regulatory effects of cytokines and cyclosporine A on peripheral blood mononuclear cells from stable multiple sclerosis patients.

The proliferative response (PR) of peripheral blood mononuclear cells (PBMC) to lectins such as phytohemaglutinin (PHA), anti-CD3 monoclonal antibodies such as OKT-3 or phorbol esters such as tetradecanoyl-phorbol 13-acetate (TPA) was investigated in 18 stable multiple sclerosis (MS) patients (9 untreated and 9 treated patients) and 10 healthy controls. PBMC from untreated MS patients showed a significantly higher PR to PHA than healthy controls. The PR of PHA, anti-CD3 or TPA stimulated PBMC from treated patients was lower than that from untreated MS patients. Mitogen stimulated PBMC from untreated patients shown both increased sensitivity to the stimulatory effect of IL-2 and increased resistance to the inhibitory effect of IL-10 and IFN-alpha. The addition of IL-2 increased the PR in PHA-stimulated PBMC from untreated MS patients, but not in those from treated MS patients and healthy controls. Mitogen stimulated cells from untreated patients were more resistant to the inhibitory effect of IL-10 and IFN-alpha than PBMC from either treated MS patients or healthy controls. Cyclosporine A (CsA) inhibited the PR and the expression of activation antigens induced by PHA in PBMC from the three groups of subjects. This inhibitory effect of CsA have was enhanced by the addition of IFN-alpha.

Adult↗
PubMed1999

Abnormal functional behavior of peripheral blood mononuclear cells from Hashimoto's disease patients. Immunomodulatory effects of cyclosporin A.

In vitro studies of activation and proliferation induced by mitogens in the presence of Cyclosporin A (CsA) and or cytokines were carried out to determine the effects of CsA and cytokines on mitogen activated peripheral blood mononuclear cells (PBMC) from thirteen Hashimoto's disease patients (HP) and ten healthy controls. The proliferative response (PR) of PBMC from HP to mitogens at 7 days of culture was higher than in controls. Interleukin 2 (IL-2) addition significantly increased the PR in phytohemagglutinin-stimulated PBMC from HP, but not in controls. CsA inhibited in a dose dependent manner the PR, as well as the expression of activation antigens induced by mitogens in both groups of subjects, but PBMC from HP were sensitive to CsA at lower doses than those that were effective on PBMC from controls. Both IL-2 or IL-4 overcame the inhibitory effect of CsA on PBMC from HP and controls. Conversely, IL-10 or IFN-alpha addition increases the inhibitory effect of CsA on the PR of PBMC from both HP and controls. We conclude that PBMC from Hashimoto's disease patients shown an abnormal pattern of PR that is associated to increased PR to mitogens and higher sensitivity to immunomodulatory effects of IL-2 and CsA.

Adjuvants, Immunologic↗
PubMed1997

An extract of the fern Polypodium leucotomos inhibits human peripheral blood mononuclear cells proliferation in vitro.

An alcoholic extract of the fern polypodium leucotomos (PLE) has been empirically used as an immunosuppressor for the treatment of several autoimmune diseases. In this paper, we investigated the effects of PLE on activation and proliferative responses of peripheral blood mononuclear cells (PBMNC) from healthy donors to T lymphocyte polyclonal mitogens. PLE shows a significant inhibitory effect on the proliferative response of PBMNC to stimulation with phytohaemagglutinin (PHA) or anti CD3 monoclonal antibodies (p < 0.05). In contrast, PLE did not modify the proliferative response of PBMNC to phorbol esters (p > 0.05). The inhibitory effect of PLE upon mitogen induced PBMNC proliferation is time dependent and can be overcome by the exogenous addition of interleukin-2 to the culture medium (p < 0.05). The decreased proliferative response of PBMNC to PHA stimulation in the presence of PLE is not associated with a significant modification of expression of the alpha chain (CD25) of the IL-2 receptor (p > 0.05). In conclusion, PLE shows an inhibitory effect on the polyclonal proliferative response of PBMNC to T lymphocyte mitogens that interact with cytoplasmic membrane molecules.

Adult↗
PubMed1994

Intracavitary prophylactic treatment with interferon alpha 2b of patients with superficial bladder cancer is associated with a systemic T-cell activation.

The activation and proliferation of peripheral blood mononuclear cells (PBMNCs) are complex processes involving several surface molecules, cell secretion and response to cytokines. This paper investigates the immunomodulatory effect of prophylactic treatment with interferon alpha 2b (IFN-alpha 2b) upon the blastogenic response of PBMNCs from patients with superficial transitional cell carcinoma (STCC) of the bladder to mitogenic signals that interact with surface molecules [phytohaemagglutinin, PHA and anti-CD3 monoclonal antibodies, (MAbs)]. PBMNCs from the patients were studied prior to the transurethral resection (TUR) of the tumour, during the second month of prophylactic intravesical instillation of IFN-alpha 2b and 3 and 6 months after finishing the instillation treatment. The [3H]thymidine uptake of PBMNCs from 17 patients with STCC of the bladder after 5 days of PHA and anti-CD3 MAb stimulus was found to be significantly lower than that of healthy controls (P < 0.05). The addition of interleukin 2 (IL-2) to the culture medium did not correct this defective proliferative response to PHA and the anti-CD3 MAb. There were no significant differences between IL-2 production in PBMNCs from STCC patients after stimulation with PHA and in PBMNCs from healthy controls (P > 0.05). Patients without evidence of recurrence showed a significantly enhanced proliferative response in PBMNC to PHA and anti-CD3 MAb after intravesical prophylactic treatment with interferon-alpha 2b in the follow-up examinations 3 and 6 months after treatment (P < 0.01). However, three patients had evidence of tumour recurrence, and they showed no enhancement of the PBMNC proliferative response to these mitogens in the same examinations. In conclusion, the prophylactic intracavitary treatment of STCC with IFN-alpha 2b may induce a systemic immunomodulatory effect which is associated to the clinical evolution of the disease.

Aged↗