Biomedical subjects
Publications and source records attributed to J Ruiz.
A case of cervical ectopic twin pregnancy with cardiac activity in both embryos is presented. It was diagnosed in the eighth week of gestation by ultrasonography, and treated conservatively with intra-amniotic administration of methotrexate under ultrasonographic guidance followed by curettage. This procedure allows subsequent gestations.
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We studied the frequency of mutation of clinical isolates of Neisseria gonorrhoeae (two nalidixic acid susceptible and two nalidixic acid resistant), and the stability of the mutants obtained, in the presence of three different concentrations of five fluoroquinolones. The frequency of mutation was low for all the quinolones. Only one N. gonorrhoeae mutant, obtained with trovafloxacin at 4 x MIC presented a stable increase in the MIC of this quinolone, not attributable to novel mutation(s), both in the gyrA and parC genes, although not showing any increase in the MIC of the other quinolones tested. In summary, gemifloxacin was the only quinolone tested for which resistant mutants were not obtained.
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Woodchuck hepatitis virus (WHV) and hepatitis B virus (HBV) are closely similar with respect to genomic organization, host antiviral responses, and pathobiology of the infection. T-cell immunity against viral nucleocapsid (HBcAg or WHcAg) has been shown to play a critical role in viral clearance and protection against infection. Here we show that vaccination of healthy woodchucks by gene gun bombardment with a plasmid coding for WHcAg (pCw) stimulates proliferation of WHcAg-specific T cells but that these cells do not produce significant levels of gamma interferon (IFN-gamma) upon antigen stimulation. In addition, animals vaccinated with pCw alone were not protected against WHV inoculation. In order to induce a Th1 cytokine response, another group of woodchucks was immunized with pCw together with another plasmid coding for woodchuck interleukin-12 (IL-12). These animals exhibited WHcAg-specific T-cell proliferation with high IFN-gamma production and were protected against challenge with WHV, showing no viremia or low-level transient viremia after WHV inoculation. In conclusion, gene gun immunization with WHV core generates a non-Th1 type of response which does not protect against experimental infection. However, steering the immune response to a Th1 cytokine profile by IL-12 coadministration achieves protective immunity. These data demonstrate a crucial role of Th1 responses in the control of hepadnavirus replication and suggest new approaches to inducing protection against HBV infection.
The extraordinary versatility of gene therapy opens new possibilities for the treatment of incurable diseases, including hepatocellular carcinoma. Gene therapy strategies against tumors include prodrug activation therapy by the transfer of suicide genes, immunogene therapy, tumoral cell phenotype correction by the inhibition of oncogenes or the transfer of tumor suppressor genes, antiangiogenesis and transfer of oncolytic viruses. The experience accumulated during the last decade of clinical gene therapy indicates that genes can be expressed inside the tumor tissue, but the overall results of the studies conducted so far are still disappointing, mainly due to the poor performance of the currently available gene therapy vectors. This review covers the general aspects of gene therapy vectors, preclinical data available in animal models of hepatocellular carcinoma, and finally a brief summary of the gene therapy clinical trials aimed at the treatment of liver cancer.
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INTRODUCTION: In order to study whether the removal of potassium in haemodialysis patients could be increased, we analyzed the kinetics of potassium transfer in the dialyzer. METHOD: 40 patients were included in the study. We studied: a) in vitro potassium exchanges between erythrocytes and plasma; b) plasma and erythrocyte potassium concentrations at dialyzer input and output; c) potassium transfers into the dialysate, using plasma clearance and direct measurement in the collected dialysate and d) erythrocyte potassium concentrations at the beginning and the end of dialysis. RESULTS: In vitro, there is virtually no potassium transfer between erythrocytes and plasma. In vivo, erythrocyte potassium concentration is not affected by the dialyzer (98.7 +/- 6.4 mmol/l to 97.7 +/- 7.5 mmol/l, p = NS). Potassium transfer levels determined by calculated plasma clearance were similar to values obtained by measuring potassium in dialysate (0.71 +/- 0.10 mmol/min vs 0.68 +/- 0.10 mmol/min, p = NS). These results suggest that erythrocytes do not participate in potassium exchange in the dialyzer. This was confirmed by measured erythrocyte potassium concentrations, which were the same at the beginning and the end of dialysis (104.0 +/- 5.6 mmol/l vs 104.2 +/- 5.0 mmol/l, p = NS).
BACKGROUND: Asymptomatic pulmonary embolism (PE) is a common finding in patients with deep venous thrombosis (DVT) of the lower limbs, but the usefulness of seeking for silent PE in patients with acute DVT has not been evaluated. PATIENTS AND METHODS: This was a prospective study involving consecutive patients with acute symptomatic proximal DVT (confirmed by objective methods) and no clinical suspicion of PE. All patients underwent chest X-ray, ventilation-perfusion lung scan and arterial blood gases on admission, and received anticoagulant therapy. Those with scintigraphic evidence of PE underwent repeated lung scan and blood gases 7 days later. The aim of the study was to assess how many patients with silent PE develop symptoms while on heparin therapy, and in how many of them such symptoms are due to recurrent PE. RESULTS: 946 consecutive patients with acute, proximal DVT had no contraindications to full-dose anticoagulant therapy. Baseline lung scan revealed high-probability defects (silent PE) in 200 (21%). Seven of these 200 patients had symptomatic recurrences during the 7-day study period, and an inferior vena cava filter was inserted. Besides, 6 patients developed PE symptoms, but no new perfusion defects were found on repeated scan. They switched to coumarin therapy, and they did not develop any further complications. CONCLUSIONS: Lung scan in patients with symptomatic DVT and no clinical suspicion of PE may be useful, since some patients with silent PE may develop symptoms while on heparin therapy. Without a baseline scintigraphy all these patients would have been considered to have recurrent PE, and vena cava interruption could have been performed.
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Type 2 diabetes mellitus is one component of the metabolic syndrome. The treatment of the metabolic syndrome includes the control of hyperglycaemia, which represents one aspect of the management of this complex disease. Indeed, the intensive treatment of hyperglycaemia is clearly associated with the prevention of the micro- and macro-vascular complications. This review describes how to use oral antidiabetic agents: sulfonylurea, glinide, biguanide, alpha-glucosidase inhibitors and glitazone.
Barnacle muscle cells regulate their volume when exposed to anisotonic conditions. Due to their large size, these cells can be internally perfused. Interestingly, perfused cells maintain their volume regulatory properties (17,21). Thus, the osmotic properties of barnacle muscle cells can be studied under conditions in which the intracellular and extracellular osmolalities, the membrane potential (V(M)), the cell volume and the intracellular pressure can all be measured simultaneously. In this manuscript we report the effect that various rates of isosmotic (1000 mOsm x kg H2O(-1)) intracellular perfusion have on cell volume, intracellular pressure, intracellular osmolality, V(M), and the apparent sarcolemmal hydraulic water permeability (L'p). Replacement of the cytosol with the perfusate at a perfusion rate of 0.83 microl x min(-1) took 120 min. During this transition period, the cell volume increased from 45.1+/-6.9 microl to 73.7+/-5.8 microl, the intracellular osmolality decreased from 1406+/-133 to 1188+/-64 mOsm x kg H2O(-1), and the intracellular pressure underwent a transient drop of 2.8 cm H2O. After 2.5 hr of continuous perfusion at 0.83 microl min(-1), the above mentioned parameters reached steady values: the L'p was 1.35 x 10(-5) cm x sec(-1) x Osm(-1) x kg H2O(-1); cell volume was 67.2+/-6 microl; the intracellular osmolality was 1052+/-10 mOsm x kg H2O(-1); the intracellular pressure was 5.6+/-0.4 cm H2O; V(M) depolarized slowly at a rate of 0.03 mV x min(-1). Stepwise increases in the rate of perfusion (from 0.83 to 3.18 microl min(-1)) produced reversible increases in the intracellular pressure, L'p and cell volume and decreases in intracellular osmolality. We conclude that intracellular perfusion: i/ produces a transient removal of intracellular osmotically active components; ii/ promotes sarcolemmal water filtration; iii/ induces a laminar flow of perfusate at the center of the cell, and iv/ enables calculations of sarcolemmal L'p values under isosmotic conditions.
The debate over the maintenance of high diversity of tree species in tropical forests centers on the role of tree-fall gaps as a primary source of disturbance. Using a 10-year data series accumulated since Hurricane Joan struck the Caribbean coast of Nicaragua in 1988, we examined the pattern of species accumulation over time and with increased sampling of individuals. Our analysis shows that the pattern after a hurricane differs from the pattern after a simple tree-fall disturbance, and we conclude that pioneers are limited in large disturbances and thus do not suppress other species the way they do in smaller disturbances.
The ferrocenylsilylation of the phenol triallyl dendron 2, of the phenol nonaallyl dendron 4, and of the 9-, 27-, 81-, and 243-allyl dendrimers 7-10 (monitored by the disappearance of the signals of the olefinic protons in 1H NMR spectra) has been achieved using ferrocenyldimethylsilane 1 and Karstedt's catalyst in diethyl ether at 40 degrees C, yielding the corresponding ferrocenyl dendrons and dendrimers. An alternative convergent synthesis of the nonaferrocenyl dendron 5 was carried out by reaction of the triferrocenyl dendron 2 with a protected triododendron followed by deprotection. Reaction of the nonaferrocenyl dendron 5 with hexakis(bromomethyl)benzene gave the 54-ferrocenyl dendron 6. All the ferrocenyl dendron and dendrimers produce a chemically and electrochemically reversible ferrocenyl oxidation wave at seemingly the same potential. Stable platinum electrodes modified with the high ferrocenyl dendrimers were fabricated. The soluble orange-red ferrocenyl dendrimers can also be oxidized in CH2Cl2 by [NO][PF6] to the insoluble deep blue polyferrocenium dendrimers. For instance, the 243-ferrocenium dendrimer has been characterized by its Mossbauer spectrum, which is of the same type as that of ferrocenium itself. The ferrocenium dendrimers can be reduced without any decomposition back to the ferrocenyl dendrimer, indicating that these multielectronic redoxstable dendrimers behave as molecular batteries.
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Regiospecific chlorocarbonylation of the polybenzyl cores PhCH2CH2Ph, C6(CH2CH2Ph)6, 7, and CH(CH2Ph)24-1,2,4,5-C6H2, 8, in the para position of the benzyl groups gives the chlorocarbonyl derivatives 2, 9, and 10, respectively, in good yields. The octachlorocarbonyl derivative 10 reacts with Newkome's aminotripod NH2C(CH2OCH2CH2CN)3 to give the 24-nitrile dendrimer 13 which is characterized by its molecular peak in the MALDI TOF mass spectrum and with (5-aminopentyl)-1-ferrocene to give the octaferrocene complex 14. Reactions of 2, 9, and 10 with sodium methanolate in methanol gives the methyl esters 3, 15, and 16 which are reduced by LiAlH4 to the primary alcohols 4, 17, and 18; reactions of these alcohols with NaI and BF3.Et2O yield the iodomethyl derivatives 5, 19, and 20. The organoiron nucleophile [FeIICp(eta 5-C6Me5CH2)], 1, reacts with 5, 19, and 20 leading to C-C bond formation and recovery of the aromatic structure of the ligand. This reaction with 5 yields a soluble complex, [FeIICp(eta 6-C6Me5CH2CH2C6H4CH2-)]2, 6, in which the two redox groups, separated by 14 carbon atoms, are independent, being reversibly reduced at approximately the same potential in an overall two-electron wave recorded by cyclic voltammetry. The analogous reaction with 19 and 20, however, gave almost insoluble hexa- and octa-iron complexes 21 and 22 with mediocre purities.
Liver regeneration from the facultative hepatic stem cells, the oval cells, takes place in situations in which liver regeneration from pre-existing hepatocytes is prevented. Different models have been used to stimulate oval cell response. Many of them involve the use of carcinogenic agents with or without partial hepatectomy. In this study we show that adenovirus-mediated gene transfer of the suicide gene thymidine kinase followed by ganciclovir administration caused hepatotoxicity of variable intensity. Rats with moderate elevation in serum transaminases recovered normal liver architecture few weeks after adenovirus injection. In contrast, rats with severe liver damage exhibited a marked and persisting activation of oval cells accompanied by ductular hyperplasia. In some rats, such lesion eventually evolved to cholangiofibrosis and in one rat to cholangiocarcinoma. Deposition of fibronectin and increased number of hepatic stellate cells were found in association with oval cells and cholangiofibrotic lesions. Hepatocyte growth factor was hyperexpressed in the livers with intense oval cell response or ductular proliferation, suggesting a participation of this factor in those lesions. In summary, our data demonstrate activation of oval cell response after gene transfer of thymidine kinase followed by ganciclovir administration. These findings indicate that high doses of this therapy causes liver damage together with an impairment in hepatocellular regeneration.
Exposure of tilapia (Oreochromis niloticus) to water temperatures of 10-15 degrees C for 3-5 min produces physiological stress responses characterized by immediate phenotypic and immunological changes. In the present study, this general stress response was utilized as a model system to study innate immunity mediated by soluble factors and cytotoxic cells. Acute innate cytotoxic responses of nonspecific cytotoxic cells (NCC) in the peripheral blood (PBL), anterior kidney (AK) and spleen (SPL) were measured. Following temperature stress, the levels of NCC activity depended on the presence of soluble factors and on the cell compartments from which the NCC were obtained. NCC from PBL of stressed tilapia had 30x or greater cytotoxic activity compared to nonstressed PBLs from controls. NCC activity from the AK and SPL of stressed tilapia was lower than controls. Flow cytometric analysis of NCC in each tissue showed that increased cytotoxicity was not produced by increased numbers of NCC. To determine the mechanism of amplification of cytotoxicity, NCC from nonstressed tilapia were passively treated with serum from temperature stressed tilapia. Serum containing the "stress activated serum factor" (SASF) passively increased naive NCC cytotoxicity (from PBL) 3-4 fold. The cytotoxic cell response was inhibited by addition of anti-NCC monoclonal antibody 5C6. These data indicated that NCC are (at least one of) the target cells for SASF. SASF required only 15 min pre-incubation with naive NCC to activate cytotoxicity. Activation was nonreversible and concentration dependent. Pretreatment of NCC with SASF reduced the assay time required to amplify target cell cytotoxicity from 12-24 h to 6 h. SASF amplification of NCC cytotoxicity was not restricted by different histological types of target cells. Determination of select physical/chemical properties of SASF revealed: complete heat inactivation of cytotoxicity amplification following 55 degrees C and 65 degrees C pretreatment; SASF was thermostable at room temperature to 45 degrees C for 15 min; and freeze-thaw treatment reduced but did not completely remove amplification activity. The molecular weight range of SASF activity was identified in a 50-100 kDa fraction obtained by differential dialysis. SASF appears to be a protein sensitive to trypsin digestion.