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Biomedical subjects

M Dominguez

Publications and source records attributed to M Dominguez.

At least 55 records · Page 3Linked to original sources

Adverse reaction to streptokinase with multiple systemic manifestations.

We report the case of a 47-year-old woman with a history of mitral valve replacement with a mechanical prosthesis who was admitted to the hospital with a 3-month history of progressive exertional dyspnoea and was diagnosed as suffering from prosthetic valve thrombosis. Two consecutive courses of streptokinase were given as an intravenous infusion over 90 min at a dose of 1,500,000 IU each. Twenty minutes after the start of the second infusion (3 h and 20 min after the first one) she developed chills, fever, tachycardia and hypotension: symptomatic treatment was given and the infusion was completed. Two days later jaundice and choluria appeared with laboratory findings of hepatic cytolysis and cholestasis and renal insufficiency. The results of extensive microbiological and immunological investigations were not revealing. All the laboratory values spontaneously returned to baseline levels over the next 4 weeks. These abnormalities were attributed to an allergic reaction to streptokinase, although the exact pathogenic mechanisms involved are not known. We believe that further studies to elucidate the mechanism involved in the production of these effects are warranted in view of their potential clinical severity.

Female↗

The yeast proprotein convertase encoded by YAP3 is a glycophosphatidylinositol-anchored protein that localizes to the plasma membrane.

The yeast YAP3 gene encodes an aspartyl endoprotease that cleaves precursor proteins at selected pairs of basic amino acids and after single arginine residues. Biosynthetic studies of this proprotein processing enzyme indicate that Yap3 is predominantly cell-associated and migrates as a approximately 160-kDa protein on SDS-polyacrylamide gel electrophoresis. Nearly equal amounts of Yap3 are immunodetected in a-haploid, alpha-haploid, and a/alpha-diploid yeast, demonstrating that the expression of YAP3 is not mating type-specific. As shown by endoglycosidase H treatment, which drastically reduces both the estimated molecular mass and the heterogeneity of the protein on SDS-polyacrylamide gel electrophoresis (68 versus 160 kDa), the oligosaccharides N-linked to the protein are subjected to extensive outer chain mannosylation. Outer chain sugar mannosylation takes place in the Golgi apparatus and is commonly found on yeast secreted glycoproteins and/or cell wall mannoproteins. Treatment of the total yeast membranes with chemical agents known to disrupt protein-protein and protein-lipid interactions reveal that Yap3 is membrane-associated. Based upon the release of the membrane-bound form by bacterial phosphatidylinositol phospholipase C digestion and metabolic labeling of the protein with myo-[3H]inositol, Yap3 owes its association with the membrane to the addition of a glycophosphatidylinositol anchor. The cellular localization of Yap3 has been addressed by subcellular fractionation studies. In both differential centrifugation of intracellular organelles and sucrose density gradients, the bulk of Yap3 at steady state co-localizes with the plasma membrane azide-insensitive ATPase. Furthermore, consistent with the transport of Yap3 to the plasma membrane, the endoprotease sediments with secretory vesicles which accumulate at restrictive temperature in the late secretory mutant sec1-1. We therefore conclude that the endoprotease encoded by YAP3 is a glycophosphatidylinositol-anchored protein, which can process substrates both intracellularly and at the cell surface.

Antibodies↗

Saccharomyces cerevisiae CNE1 encodes an endoplasmic reticulum (ER) membrane protein with sequence similarity to calnexin and calreticulin and functions as a constituent of the ER quality control apparatus.

We have used a polymerase chain reaction strategy to identify in the yeast Saccharomyces cerevisiae genes of the mammalian calnexin/calreticulin family, and we have identified and isolated a single gene, CNE1. The protein predicted from the CNE1 DNA sequence shares some of the motifs with calnexin and calreticulin, and it is 24% identical and 31% similar at the amino acid level with mammalian calnexin. On the basis of its solubility in detergents and its lack of extraction from membranes by 2.5 M urea, high salt, and sodium carbonate at pH 11.5, we have established that Cne1p is an integral membrane protein. However, unlike calnexins, the predicted carboxyl-terminal membrane-spanning domain of Cne1p terminates directly. Furthermore, based on its changed mobility from 76 to 60 kDa after endoglycosidase H digestion Cne1p was shown to be N-glycosylated. Localization of the Cne1p protein by differential and analytical subcellular fractionation as well as by confocal immunofluorescence microscopy showed that it was exclusively located in the endoplasmic reticulum (ER), despite the lack of known ER retention motifs. Although six Ca(2+)-binding proteins were detected in the ER fractions, they were all soluble proteins, and Ca2+ binding activity has not been detected for Cne1p. Disruption of the CNE1 gene did not lead to inviable cells or to gross effects on the levels of secreted proteins such as alpha-pheromone or acid phosphatase. However, in CNE1 disrupted cells, there was an increase of cell-surface expression of an ER retained temperature-sensitive mutant of the alpha-pheromone receptor, ste2-3p, and also an increase in the secretion of heterologously expressed mammalian alpha 1-antitrypsin. Hence, Cne1p appears to function as a constituent of the S. cerevisiae ER protein quality control apparatus.

Amino Acid Sequence↗

Identification and biotyping of Acinetobacter spp. isolated in Chilean hospitals.

Two hundred and eighty-one isolates of Acinetobacter spp. obtained from clinical specimens in hospitals from five Chilean cities were identified to species level and biotyped. Respiratory tract and wound secretions were the main sources of the isolates. Acinetobacter baumannii was the most frequent species (96.8%), followed by Acinetobacter genospecies 3 (2.8%). Twelve different biotypes of A. baumannii strains were found of which biotypes 9, 8 and 6 were the most frequent. Isolates of other biotypes were rare. These results differ from most other Latin American and European countries.

Acinetobacter↗

Immunomodulation by theophylline in asthma. Demonstration by withdrawal of therapy.

Theophylline is the most widely used anti-asthma drug worldwide and is classified as a bronchodilator, although there is increasing evidence that it may have immunomodulatory effects. We have investigated the effects of theophylline withdrawal under placebo control in 27 asthmatic patients (25 to 70 yr) treated with long-term theophylline who were also treated with high dose inhaled corticosteroids. We measured asthma symptoms (diary card), lung function (spirometry and home records of peak expiratory flow), and peripheral leukocyte populations using dual color flow cytometry. In eight of these patients, we examined fiberoptic bronchial biopsies by immunocytochemistry. We also studied peripheral blood lymphocytes in eight asthmatic patients who have never received theophylline. Mean steady state plasma theophylline concentrations during theophylline therapy were 8.6 +/- 0.9 mg/L. Theophylline withdrawal was associated with a significant increase in asthma symptoms, particularly at night, and a fall in spirometry and morning peak flow. This was accompanied by a significant fall in peripheral blood monocytes (CD14+, activated CD4+ T-lymphocytes (CD4+/CD25+) and activated CD8+ T-cells (CD8+/HLA-DR+) in patients with a plasma theophylline > 5 mg/L. The lymphocyte populations in theophylline-naive patients were similar to those found after theophylline withdrawal. Bronchial biopsies showed a mirror image of the peripheral blood with an increase in CD4+ and CD8+ lymphocytes in the airway. Chronic treatment with theophylline, even at low plasma concentrations, controls asthma symptoms and has effects on T-lymphocyte populations in the peripheral blood which are the inverse of those observed in the airways.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗

Activity of imipenem, third-generation cephalosporins, aztreonam and ciprofloxacin against multi-resistant gram-negative bacilli isolated from Chilean hospitals.

The activity of imipenem against nosocomial strains of Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter spp. and methicillin-resistant Staphylococcus aureus resistant to some third-generation cephalosporins, aztreonam, or ciprofloxacin was assessed. These strains represent the most prevalent multi-resistant nosocomial microorganisms in Chile since they were isolated from clinical specimens in 11 Chilean hospitals. A high proportion of the strains were resistant to several beta-lactams, yet all strains of K. pneumoniae and Acinetobacter spp. were susceptible to imipenem; resistance was exhibited by only one strain of P. aeruginosa and 16 strains of S. aureus. Synergy between cefotaxime and clavulanic acid was found in almost all strains of K. pneumoniae, suggesting the presence of plasmid-coded beta-lactamases, probably with extended-spectrum activity. Killing A. baumannii by imipenem was rapid, but slower for P. aeruginosa. Killing of K. pneumoniae was also somewhat slower despite the lower MIC of imipenem for this strain. Bactericidal activity was even slower against one strain of methicillin-resistant S. aureus. These results suggest that imipenem would be an adequate alternative to other broad-spectrum agents in the treatment of infections due to nosocomial multi-resistant Gram-negative bacilli.

Anti-Bacterial Agents↗

Primary human adult lung epithelial cells in vitro: response to interferon-gamma and cytomegalovirus.

Primary human adult lung epithelial cells (ALEC) were established in culture using the most distal parts of the lung to avoid the airways. Immunocytochemical peroxidase staining and semiquantitative flow cytometry were used to characterize the cells in conjunction with a panel of monoclonal antibodies (mAb). The cells showed a constitutive expression of major histocompatibility complex (MHC) class I antigens, patchy expression of intercellular adhesion molecule-1 (ICAM-1) and a weak patchy expression of MHC class II antigens (detected using immunocytochemical staining). Incubation of the primary ALEC with interferon-gamma (IFN-gamma) (250 U/ml) stimulated an up-regulation of the expression of these three antigens to varying degrees; expression of MHC class I antigens and ICAM-1 molecules showed an up-regulation at 10 hr after the start of the treatment, reaching a peak at 48 hr, maintaining it for the next 24 hr and then, steadily and progressively, losing it towards the end of the experiment at 96 hr. Expression of HLA-DR showed an up-regulation at 17 hr after the start of the treatment, reaching a peak at 72 hr and maintaining it for the next 24 hr. Cytomegalovirus (CMV) infection of ALEC in culture caused an up-regulation of expression of class I antigens and ICAM-1, but not DR. However, when the infected cells were incubated with IFN-gamma, an up-regulation in the expression of DR took place. Therefore, within the micro-environment of the transplanted lung the presence of cytokines (IFN-gamma) produced by infiltrating activated mononuclear cells, may render the lung epithelial cells capable of acting as antigen-presenting cells, expressing high levels of class I antigens, ICAM-1 and class II antigens, activating CD8 and CD4 cells thus playing a major part in the process of rejection of the lung allograft; themselves becoming a primary target in the process.

Adult↗

[Prevalence of gastrocnemius vein insufficiency using color-coded Doppler ultrasound (modifications of the therapeutic strategy)].

The importance of morphologic and dynamic lesions of the gastrocnemius vein is underestimated. Color-coded Duplex scanning was performed in 483 patients with varicosities and 869 legs with some venous abnormalities were discovered. Two types of lesion on gastrocnemius veins were founded: incompetence and dilatation usually located on the medial gastrocnemius vein. In 29.34% of the limbs, a medial gastrocnemius vein incompetence was present and a dilatation in 15.42%. Medial gastrocnemius vein incompetence was associated with a mid calf gastrocnemius communicating vein incompetence in 25%. Physiopathological hypothesis could be drawn of our observations. Gastrocnemius veins when incompetent should be ligated flush to the popliteal vein. The high prevalence of gastrocnemius vein should be considered in the management of varicose veins and color-coded Duplex scanning routinely performed before surgery.

Adult↗

[Is A29, B12 vasculitis caused by the Q fever agent? (Coxiella burnetii)].

The authors describe the first two cases, to their knowledge, of retinal vasculitis, associated with Q fever. The first case was a chronic infection induced by Coxiella burnetii associated with HLA group A29 and B12; in the second case, the phenotype was B12. The authors tried to determine whether this agent could be the "Birdshot chorioretinopathy" promoting factor. Several epidemiologic findings tend to prove that Q fever is not the only cause. On the other hand, its similarity with rickettsia, the fact that it is found in patients with vasculitis, suggest that it could be one of the initial causal factors.

Adult↗

Susceptibility to antimicrobial agents and plasmid carrying in Aeromonas hydrophila isolated from two estuarine systems.

Susceptibility to various antimicrobial agents and the presence of plasmids was investigated in eleven strains of Aeromonas hydrophila isolated from samples of sea water and these strains isolated from Aulacomya ater. Transference of resistance to Escherichia coli was attempted by conjugation and transformation experiments. The strains showed multiple resistance toward beta-lactam antibiotics and susceptibility to other antimicrobial agents. Five strains harboured plasmids with molecular weights below 5.7 MD. It was not possible to relate the resistance of the strains with the presence of their plasmids.

Aeromonas hydrophila↗

Intrathecal synthesis of soluble class I antigens (sHLA) in patients with HIV infection and tuberculous meningitis.

sHLA are soluble class I antigens produced by lymphocytes on early activation. We have studied the sHLA index IH = (CSF sHLA/serum sHLA)/(CSF albumin/serum albumin), which reflects the intrathecal synthesis (ITS) of sHLA in 23 intravenous drug abusers with central nervous system (CNS) HIV infection. Their mean IH value was increased and directly correlated with ITS of IgG against HIV when the total group of patients was studied; however, 8 of them, who suffered from concomitant tuberculous meningitis, had a decreased IH. The relationship between this index, blood-brain barrier (BBB) function, and HIV and tuberculous infection was also studied. We consider IH an index of lymphocyte activation within the CNS. Its decrease in patients with CNS HIV infection may reflect the presence of a meningeal opportunistic infection due to Mycobacterium tuberculosis.

AIDS Dementia Complex↗

Soluble class 1 antigens (sHLA) in CSF and serum of patients with HIV infection.

sHLA are secreted by B and T lymphocytes upon activation. These antigens are present in serum and cerebrospinal fluid (CSF). The establishment of a sHLA index, IH = (CSF sHLA/serum sHLA)/(CSF albumin/serum albumin) helped us to define that values above 9.7 reflect an intrathecal synthesis of these proteins. IH was significantly increased in a group of patients with intrathecal production of IgG against HIV-1 (HIV) and directly correlated with the synthesis of such antibodies. Therefore, IH seems to be an index of lymphocyte activation in CNS.

HIV Infections↗

[Malaria and retinal hemorrhages].

A 24-year-old woman presented with retinal hemorrhages, back from a travel in Cameroon. She took a chloroquine chemoprophylaxis. We diagnosed a malaria due to Plasmodium falciparum with anemia, splenomegaly and low parasitemia. A speedy clinical and ophthalmological recovery was obtained with mefloquine therapy. We discuss physiopathology of such uncommon retinal damage during malaria.

Adult↗

Analysis of T cell subpopulations and cyclosporine levels in the blood of two neonates born to immunosuppressed heart-lung transplant recipients.

The influence of continuous immunosuppression on the immune system of 2 neonates born to heart-lung transplant recipients was analyzed. T cells, T cell subpopulations, B cells and cyclosporine levels were measured in maternal and cord blood at the time of delivery. Cyclosporine, both parent compound, and metabolites were found in cord blood but in lower amounts than that in the mother. This discrepancy was more pronounced for parent compound than metabolites. Infants born to immunosuppressed mothers had more T and B cells than the mother and had similar numbers of T and B cells to that found in cord blood from 10 babies born to nonimmunosuppressed mothers. One infant had fewer activated T cells and a higher CD4/CD8 ratio due to increased numbers of CD4 cells than normal. In conclusion, neither of these babies had a lymphocyte profile suggestive of chronic immunosuppression.

Antigens, Differentiation↗

Spinal cord stimulation for relief of chronic pain in vasospastic disorders of the upper limbs.

Eleven patients with chronic pain due to severe vasospastic disorders in the upper limbs were treated with cervical spinal cord stimulation. In 8 patients the pain was due to reflex sympathetic dystrophy in the late stage of the disease, and 3 patients had severe idiopathic Raynaud's disease. The mean follow-up for both groups was 27 months. A total of 10 patients (90.9%) had good or excellent results. Thermographic and plethysmographic changes were observed in both groups. There seems to be a very close relationship between the increase of blood flow and the amount of pain relief achieved. In an attempt to quantify the intensity of pain, the visual analog scale and McGill Pain Questionnaire were used. Stimulation proved to be harmless, with no mortality and very low morbidity. The latter centered around local infection and displacement of the electrodes. No objective changes occurred in trophic alterations such as bone decalcification and ankylosis, but there were improvements in the alterations in the nails and skin. In the reflex sympathetic dystrophy group, the amount of pain relief achieved enabled most patients to undergo subsequent physiotherapy and rehabilitation. In severe cases of reflex sympathetic dystrophy and idiopathic Raynaud's disease, spinal cord stimulation is an alternative treatment that can be used as primary therapy or as secondary therapy after unsuccessful sympathectomy or sympathetic blocks.

Adult↗