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Biomedical subjects

Francisco Medina

Publications and source records attributed to Francisco Medina.

12 recordsLinked to original sources

Rheumatic manifestations of human immunodeficiency virus infection.

Rheumatic complaints are common in patients with HIV, and HIV positivity confers an increased susceptibility in populations with similar risk factors for HIV infection. With the advent of the modern combined antiretroviral treatment, HAART has had a profound beneficial effect on survival in HIV-infected patients, with lifelong control of HIV infection and normalization of life expectancy; but it has also contributed to both an altered frequency and a different nature of rheumatic complications now being observed in this population, with new rheumatic complications, such as osteoporosis, osteonecrosis, gout, mycobacterial, mycotic osteoarticular infections, and neoplasia perhaps more prevalent. Rheumatologists, internists, and general physicians need to be aware of these changes to provide optimal diagnosis and how to disclose the results to their patients. They also need to be familiar with the management of HIV infection and to direct careful attention to the prevention of HIV transmission in health care facilities.

Animals↗

Pore size distribution analysis of selected hexagonal mesoporous silicas by grand canonical Monte Carlo simulations.

We combine here a regularization procedure with individual adsorption isotherms obtained from grand canonical Monte Carlo simulations in order to obtain reliable pore size distributions. The methodology is applied to two hexagonal high-ordered silica materials: SBA-15 and PHTS, synthesized in our laboratory. Feasible pore size distributions are calculated through an adaptable procedure of deconvolution over the adsorption integral equation, with two necessary inputs: the experimental adsorption data and individual adsorption isotherms, assuming the validity of the independent pore model. The application of the deconvolution procedure implies an adequate grid size evaluation (i.e., numbers of pores and relative pressures to be considered for the inversion, or kernel size), the fulfillment of the discret Picard condition, and the appropriate choice of the regularization parameter (L-curve criteria). Assuming cylindrical geometry for both porous materials, the same set of individual adsorption isotherms generated from molecular simulations can be used to construct the kernel to obtain the PSD of SBA-15 and PHTS. The PSD robustness is measured imposing random errors over the experimental data. Excellent agreement is found between the calculated and the experimental global adsorption isotherms for both materials. Molecular simulations provide new insights into the studied systems, pointing out the need of high-resolution isotherms to describe the presence of complementary microporosity in these materials.

Adsorption↗

Macrophage migration inhibitory factor promotes intestinal tumorigenesis.

BACKGROUND & AIMS: The cytokine macrophage migration inhibitory factor (MIF) is expressed throughout the human gastrointestinal tract. Recently, protumorigenic activity of MIF has been described in several cancer models. Therefore, we investigated the expression and function of MIF during the early stages of intestinal tumorigenesis. METHODS: MIF messenger RNA, protein, and tautomerase activity were measured in normal intestinal mucosa and adenomas from patients with sporadic colorectal adenomas and in the adenomatous polyposis coli (Apc)Min/+ mouse model of intestinal tumorigenesis. MIF function was investigated by using VACO-235 human colorectal adenoma cells in vitro and by testing the effect of genetic deletion of Mif on ApcMin/+ mouse intestinal tumorigenesis. RESULTS: MIF expression and tautomerase activity were increased in human and ApcMin/+ mouse intestinal adenomas compared with adjacent normal mucosa. Up-regulation of MIF occurred mainly in epithelial cells (associated with an increasing grade of dysplasia), but also in stromal plasma cells. Exogenous MIF inhibited apoptosis and promoted anchorage-independent growth of VACO-235 cells (maximal at 100 ng/mL). Homozygous deletion of Mif was associated with a reduction in the number and size of ApcMin/+ mouse adenomas (P = .025 for the difference in large [>7-mm] tumors) and decreased angiogenesis (43% decrease in mean tumor microvessel density), but there was no alteration in epithelial cell apoptosis or proliferation. CONCLUSIONS: MIF expression is increased in sporadic human colorectal adenomas, and exogenous MIF drives tumorigenic behavior of epithelial cells in vitro. Mif also promotes intestinal tumorigenesis (predominantly via angiogenesis) in the ApcMin/+ mouse. Therefore, MIF is a potential colorectal cancer chemoprevention target.

Adenoma↗

Sjögren syndrome associated with hepatitis C virus: a multicenter analysis of 137 cases.

To define the clinical and immunologic pattern of expression of Sjögren syndrome (SS) associated with chronic hepatitis C virus (HCV) infection, we conducted a multicenter study aiming to collect a large number of patients with SS and HCV infection. Inclusion criteria were the fulfillment of at least 4 of the classification criteria for SS proposed by the European Community Study Group and repeated positive HCV serology, confirmed by recombinant immunoblot assay and/or detection of serum HCV-RNA by polymerase chain reaction. One hundred thirty-seven patients were included (104 female and 33 male; mean age, 65 yr). Seventy-nine (58%) patients presented a systemic process with diverse extraglandular manifestations, with articular involvement (44%), vasculitis (20%), and neuropathy (16%) being the most frequent features observed. The main immunologic features were antinuclear antibodies (65%), hypocomplementemia (51%), and cryoglobulinemia (50%). Cryoglobulins were associated with a higher frequency of cutaneous vasculitis, rheumatoid factor, and hypocomplementemia. Thirty-two (23%) patients had positive anti-Ro/SS-A and/or anti-La/SS-B antibodies; these patients were predominantly women and had a higher prevalence of some extraglandular features and a lower frequency of liver involvement. Nineteen (14%) patients developed neoplasia, with hematologic neoplasia (8 cases) and hepatocellular carcinoma (6 cases) being the most frequent types. Eighty-five percent of SS-HCV patients also fulfilled the recently proposed 2002 classification criteria for SS. In conclusion, HCV-associated SS is indistinguishable in most cases from the primary form using the most recent set of classification criteria. Chronic HCV infection should be considered an exclusion criterion for the classification of primary SS, not because it mimics primary SS, but because the virus may be implicated in the development of SS in a specific subset of patients. We propose the term "SS secondary to HCV" when these patients fulfill the 2002 classification criteria for SS.

Adult↗

Clinical features related to antiphospholipid syndrome in patients with chronic viral infections (hepatitis C virus/HIV infection): description of 82 cases.

We analyzed the spectrum of clinical features related to antiphospholipid syndrome (APS) in patients with chronic viral infections, such as hepatitis C virus (HCV) infection and human immunodeficiency virus (HIV) infection. We selected patients from the HISPAMEC registry who repeatedly tested positive for antiphospholipid antibodies (aPL) and who had features of APS, and we searched the MEDLINE database for additional cases. A total of 82 patients were included (45 had chronic HCV infection, 32 had HIV infection, and 5 had HCV-HIV coinfection). The main features of APS were avascular bone necrosis (20 patients), peripheral thrombosis (17), thrombocytopenia (15), neurologic features (13), cardiac manifestations (12), pulmonary embolism (9), gastrointestinal manifestations (8), and cutaneous manifestations (8). The main APS-related features in HCV-infected patients were intraabdominal thrombosis and myocardial infarction, whereas, in HIV-infected patients, the main features were avascular bone and cutaneous necrosis. These viruses might act in some patients as chronic triggering agents that induce a heterogeneous, atypical presentation of APS.

Adult↗

Purification of human lamina propria plasma cells by an immunomagnetic selection method.

Plasma cells (PC) are the terminal stage of B-lymphocyte differentiation and, as such, they are dedicated to large-scale secretion of antibodies (Ab). Bone marrow (BM) and lamina propria (LP) become the final reservoirs of PC generated in response to systemic and mucosal antigen stimulation, respectively. Although the majority of human PC are held in the mucosa LP, they have received less attention than PC present in other locations. A key step for many PC studies is the design of isolation protocols to purify them. A purification procedure for LPPC has not been described as yet and, therefore, we decided to develop a protocol for this purpose, comprising three main steps: (1) dissecting LP from colonic tissue; (2) releasing LP cells by a short 15-min collagenase digestion; (3) isolating LPPC by positive immuno-magnetic selection using the distinctive expression of CD54 (ICAM-I) on LPPC. By following this protocol, a viable, highly purified LPPC fraction can be obtained in less than 2 1/2 h.

ADP-ribosyl Cyclase↗

Shifting immunodominance pattern of two cytotoxic T-lymphocyte epitopes in the F glycoprotein of the Long strain of respiratory syncytial virus.

Human respiratory syncytial virus (RSV) is a major cause of respiratory infection in children and in the elderly. The RSV fusion (F) glycoprotein has long been recognized as a vaccine candidate as it elicits cytotoxic T-lymphocyte (CTL) and antibody responses. Two murine H-2K(d)-restricted CTL epitopes (F85-93 and F92-106) are known in the F protein of the A2 strain of RSV. F-specific CTL lines using BCH4 fibroblasts that are persistently infected with the Long strain of human RSV as stimulators were generated, and it was found that in this strain only the F85-93 epitope is conserved. Motif based epitope prediction programs and an F2 chain deleted F protein encoded in a recombinant vaccinia virus enabled identification of a new epitope in the Long strain, F249-258, which is presented by K(d) as a 9-mer (TYMLTNSEL) or a 10-mer (TYMLTNSELL) peptide. The results suggest that the 10-mer might be a naturally processed endogenous K(d) ligand. The CD8(+) T-lymphocyte responses to epitopes F85-93 and F249-258 present in the F protein of RSV Long were found to be strongly skewed to F85-93 in in vitro multispecific CTL lines and in vivo during a secondary response to a recombinant vaccinia virus that expresses the entire F protein. However, no hierarchy in CD8(+) T-lymphocyte responses to F85-93 and F249-258 epitopes was observed in vivo during a primary response.

Amino Acid Motifs↗

Internodal myelinated segments: delay and RGC time-domain Green function model.

The myelinated axon can be modeled by means of a distributed RGC circuit. The Green function of this model allows for a generic formulation of the internodal segment response to any kind of stimulus, and accounts for the delay of the action potential associated with this segment. The RGC model accuracy is comparable to that of a more complex electromagnetic model, and predicted delay agrees with experimental measurements.

Action Potentials↗

Oxidation of activated carbon: application to vinegar decolorization.

This article reports studies on the feasibility of increasing the decoloring capacity of a granular activated carbon (GAC) by using oxidation with air at 350 degrees C to modify its surface activity and porosity. The GAC, obtained from olive stones, had a maximum decolorization capacity of 92% for doses of 20 g/l, while the maximum decolorization capacity of the modified granular activated carbon (MGAC) was about 96% at a dose of 10 g/l. The increase in decoloring capacity is thought to be due to an increase in mesopore area (from 129 to 340 m2/g) in the MGAC. The maximum decoloring values and the doses needed to attain them are very close to values obtained in previous studies using coconut shell powder-activated carbon (94 and 98% for red and white vinegar for a dose of 10 g/l, respectively).

Acetic Acid↗

The heterogeneity shown by human plasma cells from tonsil, blood, and bone marrow reveals graded stages of increasing maturity, but local profiles of adhesion molecule expression.

Plasma cells (PCs) are the final B-cell differentiation stage. Recent evidence reveals relevant functional differences within the PC compartment. In rodents, early PCs formed in secondary lymphoid tissues show enhanced apoptosis and short life span, whereas PCs present in a final destination organ, such as the bone marrow (BM), have reached a stable prolonged survival state. BM PCs arrive at this organ as a circulating precursor whose cellular nature remains uncertain. An initial aim of this study was to characterize this circulating cell. We hypothesized that antibody-secreting cells detectable in the human blood after immunization might be a candidate precursor. These cells were obtained from the blood of volunteers immunized 6 days earlier with tetanus toxoid (tet), and they were unambiguously identified as PCs, as demonstrated by their expression of the CD38(h) phenotype, by morphology, by immunoglobulin (Ig) intracytoplasmic staining, and by IgG-tet-secreting capacity in vitro. In addition, by using the common CD38(h) feature, human PCs from tonsil (as a possible source of early PCs), from blood from tet-immunized donors (as the putative precursors of BM PCs), and from BM (as a deposit organ) have been purified and their phenotypes compared. The results show that a variety of differentiation molecules, proteins involved in the control of apoptosis, the B-cell transcription factors, positive regulatory domain I-binding factor 1/B lymphocyte-induced maturation protein 1 and B cell-specific activating protein and, at least partially, the chemokine receptor CXCR4 were expressed by human PCs following a gradient of increasing maturity in the direction: tonsil-->blood-->BM. However, PCs from these different organs showed a local pattern of adhesion molecule expression. These observations are discussed in light of the complex physiology of the human PC compartment.

ADP-ribosyl Cyclase↗

Takayasu's arteritis.

The frequency of Takayasu's arteritis (TA) has been estimated to be 2.9 cases per 1 million people, with a female preponderance, although female-to-male ratio varies from different geographic areas. A high frequency of haplotype A24-B52-DR2 has been found in Japanese patients, without this association in other populations. TA has a striking predilection for the aortic arch and its branches. Evidence favors an autoimmune pathogenesis. Segmental inflammation (active and inactive lesions) may coexist. Due to its enhanced resolution, magnetic resonance imaging and magnetic resonance angiography eventually will replace catheterization angiography. Mortality reduction with glucocorticoid treatment has not been firmly established.

Adolescent↗