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Biomedical subjects

G Marti

Publications and source records attributed to G Marti.

At least 19 recordsLinked to original sources

Image-guided surgical microscope with mounted minitracker.

A new image-guided microscope using augmented reality overlays has been developed. Unlike other systems, the novelty of our design consists in mounting a precise mini and low-cost tracker directly on the microscope to track the motion of the surgical tools and the patient. Correctly scaled cut-views of the pre-operative computed tomography (CT) stack can be displayed on the overlay, orthogonal to the optical view or even including the direction of a clinical tool. Moreover, the system can manage three-dimensional models for tumours or bone structures and allows interaction with them using virtual tools, showing trajectories and distances. The mean error of the overlay was 0.7 mm. Clinical accuracy has shown results of 1.1-1.8 mm.

Equipment Design↗

Electroporative transfection with KGF-1 DNA improves wound healing in a diabetic mouse model.

We recently demonstrated that electroporation enhances transfection in a mouse wound-healing model. Keratinocyte growth factor (KGF) is an inducer of epithelial cell proliferation and differentiation and has been shown to be under expressed in the wounds of diabetic individuals. We hypothesized that KGF delivered into an excisional wound via naked DNA injection with subsequent electroporation would be a novel and potentially effective method to enhance wound closure in a diabetic mouse model. ELISA assays confirmed production of KGF protein in cultured mouse cells and RT-PCR assays confirmed KGF mRNA in skin samples taken from mice. In all, 32 genetically diabetic mice were given two identical excisional wounds of their dorsum and split into two groups with one group receiving KGF DNA injection and electroporation with the other group receiving no treatment. Over 90% of wounds healed in the presence of KGF and electroporation versus 40% in the untreated group by day 12. Histological analysis of the wounds demonstrated that untreated wounds contained microulcers with thin or incomplete epithelium with unresolved inflammation as compared to treated wounds where intact and mature epithelium was observed. Taken together these findings suggest that a single injection of KGF DNA encoded on a plasmid coupled with electroporation improves and accelerates wound closure in a delayed wound-healing model.

Animals↗

Performance of calibration standards for antigen quantitation with flow cytometry.

In the frame of the activities initiated by the Task Force for Antigen Quantitation of the European Working Group on Clinical Cell Analysis (EWGCCA), an experiment was conducted to evaluate microbead standards used for quantitative flow cytometry (QFCM). An unified window of analysis (UWA) was established on three different instruments (EPICS XL [Coulter Corporation, Miami, FL], FACScan and FACS Calibur [Becton Dickinson, San Jose, CA]) with QC3 microbeads (FCSC, PR). By using this defined fluorescence intensity scale, the performance of several monoclonal antibodies directed to CD3, CD4, and CD8 (conjugated and unconjugated), from three manufacturers (BDIS, Coulter [Immunotech], and DAKO) was tested. In addition, the QIFI system (DAKO) and QuantiBRITE (BDIS), and a method of relative fluorescence intensity (RFI, method of Giorgi), were compared. mAbs reacting with three more antigens, CD16, CD19, and CD38 were tested on the FACScan instrument. Quantitation was carried out using a single batch of cryopreserved peripheral blood leukocytes, and all tests were performed as single color analyses. Significant correlations were observed between the antibody-binding capacity (ABC) values of the same CD antigen measured with various calibrators and with antibodies differing in respect to vendor, labeling and possible epitope recognition. Despite the significant correlations, the ABC values of most monoclonal antibodies differed by 20-40% when determined by the different fluorochrome conjugates and different calibrators. The results of this study indicate that, at the present stage of QFCM consistent ABC values may be attained between laboratories provided that a specific calibration system is used including specific calibrators, reagents, and protocols.

Antibodies, Monoclonal↗

The rubella virus putative replicase interacts with the retinoblastoma tumor suppressor protein.

In utero fetal infection of rubella virus (RV), a positive-stranded RNA virus, frequently induces birth defects if contracted in the first trimester of pregnancy. The underlying mechanism of RV-induced birth defects is not known. Birth defects are also common in certain DNA viral infections such as human cytomegalovirus (HCMV). During HCMV infection, one of its proteins interacts with a cell growth regulatory protein, the retinoblastoma protein (Rb) and stimulates DNA synthesis which is associated with chromosomal damage and cellular mitotic arrest. These affects have been implicated in HCMV induced teratogenesis. Since RV and HCMV both cause teratogenesis, we postulated that during RV infection, a virus-encoded protein might interact with Rb and affect fetal cell growth. In the present study, we have identified a known Rb-binding motif, L x C x E (LPCAE) in the carboxy-terminal half of the putative replicase (NSP90) of RV and demonstrated that the C-terminal region specifically binds to GST-Rb in vitro. Further, by coimmunoprecipitating NSP90 and Rb using specific antibodies to respective proteins, we have confirmed that NSP90 specifically binds to Rb in vivo as well. In addition, RV replication was shown to be less in null-mutant (Rb-/-) mouse embryonic fibroblast cells than in wild-type (Rb+/+) cells, suggesting a possible physiological role for this interaction. Thus, in facilitating RV replication, binding of NSP90 to Rb potentially alters the cell growth regulatory property of Rb, and this could be one of the initial steps in RV-induced teratogenesis.

Animals↗

Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in reactive and neoplastic lymphoid cells.

We have studied the expression of gelatinase A, gelatinase B, interstitial collagenase, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in reactive lymphoid cells, as well as in a series of cell lines derived from neoplasms of B- and T-cell lineage. Using both Northern blot analysis and zymography, gelatinase B activity was detected by zymography in two Burkitt cell lines and in a tonsillar cell suspension, while gelatinase A and interstitial collagenase activities were not detected by either method. TIMP-1 expression was demonstrated by Northern blot analysis in the multipotential neoplastic K-562 cell line, the high grade Burkitt's B-cell lymphoma lines, isolated tonsillar B cells and at low levels in peripheral blood T cells, but was not expressed in any of the neoplastic T-cell lines or isolated peripheral blood B cells. In contrast, TIMP-2 expression was restricted to tissues containing cells of T-cell lineage with high levels being observed in the neoplastic T-cell lines and lower levels in normal peripheral blood T cells and hyperplastic tonsil. Expression of TIMP-1 and TIMP-2 was confirmed at the protein level by reverse zymography and immunofluorescence assays using antihuman TIMP polyclonal antibodies. Expression of gelatinase B by the high grade B-cell Burkitt's lymphoma cell lines is consistent with previous findings in large cell immunoblastic lymphomas and indicates that this enzyme may play an important role in high grade non-Hodgkin's lymphomas. TIMP expression correlated with cell lineage in that TIMP-1 was primarily observed in B cells and TIMP-2 was restricted to T cells.

B-Lymphocytes↗

Percutaneous embolization of subclavian pseudoaneurysmatic arteriovenous iatrogenic fistula by steel coils.

A case of iatrogenic subclavian arterio-venous fistula with pseudoaneurysm formation is described. Treatment by means of percutaneous embolization, on the venous side, with steel coils has been successful; in order to avoid complications, the arterial side was blocked by an angioplasty balloon. After discussing the more common complications of subclavian vein puncture, the Authors conclude that percutaneous embolization is a valuable alternative to surgery even in such a lesion, especially when the surgical risk is high.

Aneurysm↗

Oligodeoxyribonucleotide phosphorothioate fluxes and localization in hematopoietic cells.

An antisense oligonucleotide phosphorothioate, previously shown to inhibit HIV-1 viral expression in chronically infected H9 cells, was fluorescently labeled to study oligonucleotide fluxes and localization within living cells. Observations based on flow cytometry and fluorescence microscopy show the following: within around 0.5-2 h, an apparent steady-state distribution of the oligonucleotide is achieved in which the intracellular oligonucleotide concentration is less than that present in the external medium; following oligonucleotide uptake and resuspension of the cells in oligonucleotide-free medium, an oligonucleotide efflux, with a time constant similar to that for uptake, is observed (although a significant fraction of the phosphorothioate remains within the cell); cellular uptake as a function of the external oligonucleotide concentration is nonlinear, being more efficient at lower concentrations (less than 2 microM); and a predominant oligonucleotide localization within the cell nucleus and perinuclear organelles is observed.

Base Sequence↗

Noninvasive assessment of the relationship between cardiac and autonomic function in diabetes.

In order to assess a possible relationship between left ventricular (LV) function and cardiac autonomic involvement in type-1 insulin dependent diabetes, we performed M-mode echocardiograms and autonomic function tests in 21 patients (mean age +/- SD, 38 +/- 11 years, range 18-55, 16 male and 5 female). In 7 patients and in 21 age-matched controls the echocardiogram was also recorded before and during handgrip. At rest, ventricular function abnormalities were found only in 4 subjects, and no significant correlation was found between echocardiographic parameters and autonomic function tests. Unlike controls, during handgrip diabetic subjects failed to increase peak Vcf and peak filling rate, and increased their left ventricular end-systolic diameter. The changes in LV parameters during handgrip were significantly correlated with resting autonomic function tests (p less than 0.025). Our results suggest that resting cardiac function may be normal in diabetics despite high incidence of abnormal autonomic tests. Latent abnormalities of left ventricular function can be unmasked by acute haemodynamic challenges such as handgrip, and are correlated with abnormalities in autonomic function tests.

Adolescent↗

Accessory function of interleukin-1 and interleukin-6: preferential costimulation of T4 positive lymphocytes.

Two monocyte-derived cytokines, interleukin-1 (IL-1) and interleukin-6 (IL-6), have been reported to costimulate monocyte-depleted T cell populations in the presence of mitogen, and this effect has been attributed to an accessory function of these molecules. We have now examined further the accessory function potential of IL-1 plus IL-6, and examined how these cytokines promote T cell growth with mitogen. Together, IL-1 and IL-6 additively and, to a small degree, synergistically promote the proliferation of highly purified human peripheral blood T cells with phytohemagglutinin (PHA). However, maximum costimulation by IL-1 plus IL-6 over a wide range of concentrations is significantly smaller than that induced by optimal numbers of monocytes. Also, in contrast to monocytes that costimulate equally effectively T4 positive and T8 positive cells, IL-1 plus IL-6 costimulate T4 positive lymphocytes in marked preference to T8 positive cells. IL-1 plus IL-6 induces IL-2 secretion in T cell cultures costimulated with PHA, and an antibody to the IL-2 receptor, anti-Tac, markedly inhibits PHA-activated T cells costimulated by IL-1 plus IL-6. In addition, IL-1 plus IL-6 enhances the expression of surface IL-2 receptors. Because the costimulatory effect of IL-1 plus IL-6 is quantitatively smaller than that of monocytes, and it is preferentially directed toward T4 positive as opposed to T8 positive T cells, IL-1 plus IL-6, together, appear to represent a selective set of monocyte-derived accessory signals.

CD4-Positive T-Lymphocytes↗

Treatment of chronic heart failure: an expert system advisor for general practitioners.

Most decision-support systems in medicine have been developed in hospital environments, but only few are designed for being used by general practitioners. The present work aims to design an expert system for practitioners in chronic heart failure (CHF) treatment. It provides assistance in defining the therapy relying on CHF aetiology, gravity, physiopathological conditions, and discriminates if other coexistent diseases and/or drugs taken by the patient could interact with CHF management. It warns the physician about the possible interactions of the considered CHF therapy. In case of contraindications, the system suggests another alternative therapy. It also advices about the control tests to follow-up the prescribed therapy, and about the indicated hygienic-dietetic suggestions. To assess its internal consistency, we examined the behaviour of the system with 20 CHF patients, by comparing the suggested therapy with the prescriptions of cardiologists. In 9 cases the suggested therapeutic schemes contained all the "n" drugs administered by the cardiologists. In 5 cases the concordance was on at least two thirds of the prescribed medications, in 5 between one half and two thirds, while in 1 case there was no concordance at all. In none of the 10 cases with partial concordance, were there major discrepancies (i.e. potentially deleterious for the patient) between the expert system's suggestions and the cardiologists' prescriptions. In conclusion, the advices of the expert system were similar to those of the cardiologists, suggesting the feasibility of such a computer support to CHF management.

Anti-Arrhythmia Agents↗

[Condylar fractures and involvement of the trigeminal nerve].

Although fractures of the condylar neck belong to the most frequent injuries of the jaws, and various nerves are found in close proximity to the temporomandibular joints, only little mention is made in the literature of the neurological complications. An unusual case of V2 and V3 nerve injury is presented. The literature is reviewed and the mechanism of the nerve injuries are discussed, 21 cases are reported.

Child↗

Immunoglobulin delta expression in Burkitt's lymphoma cell lines.

Eighteen Burkitt's lymphoma (BL) cell lines were analyzed for rearrangement and expression of the delta gene. None had rearrangement of the delta gene locus within the 9.0-kb BamHI restriction fragment. Cell lines that expressed the delta gene contained both mu alleles, with at least one productively rearranged. Thirteen of 18 cell lines had detectable transcripts hybridizing with the delta probe. In 10 of the 13 cell lines with delta transcripts, cytoplasmic delta chains were detected, but only two of these expressed delta chains strongly on the surface. All 13 lines made cytoplasmic mu chains, and all except one made cytoplasmic light chains. Surface IgM was detected in all except two of the 13 cell lines. Although BL has generally been considered not to express IgD, except in occasional cases, previous studies have been confined to examination of the cell surface. Many of the cell lines that we examined express delta mRNA transcripts as well as produce cytoplasmic delta chains but no detectable surface IgD. This suggests that delta chains are detectable in the cytoplasm prior to being apparent on the surface. Our findings argue against an origin of BL from germinal center cells since IgD is almost totally lacking in normal B cells present in germinal centers.

Africa↗

Fatal mushroom poisoning in Barcelona, 1986-1988.

In 1986-88, 46 poisonings (4 of which were fatal) caused by amatoxin mushroom were reported. The fatalities were males aged between 7 and 65 years. They all had gastrointestinal symptoms and three of the patients died of acute hepatic insufficiency. The fourth died as a result of an intestinal perforation. The clinical and pathological alterations are compared with the findings of other authors.

Adolescent↗