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Biomedical subjects

R Delgado

Publications and source records attributed to R Delgado.

At least 109 records · Page 6Linked to original sources

Sinus histiocytosis of pelvic lymph nodes after hip replacement. A histiocytic proliferation induced by cobalt-chromium and titanium.

Six men who had undergone hip replacements for degenerative joint disease or trauma subsequently had radical prostatectomies or cystoprostatectomies with bilateral pelvic lymph node dissections for adenocarcinoma of the prostate or transitional cell carcinoma of the urinary bladder. The hip prostheses implanted in three patients were known to contain cobalt-chromium alloy and titanium. The pelvic lymph nodes ipsilateral to the hip prosthesis in five patients and the bilateral pelvic nodes in the only patient with bilateral hip prosthesis had dark brown or black cut surfaces. These lymph nodes did not contain carcinoma but showed florid sinus histiocytosis characterized by large polygonal histiocytes filling and expanding sinuses and interfollicular regions. The foamy histiocytes contained cobalt-chromium and titanium microparticles by light microscopy, ultrastructure, and energy-dispersive x-ray microanalysis. The lymph nodes uninvolved by the histiocytic reaction lacked the heavy metal microparticles. Four cases were found to have a small number of polyethylene particles, which might have contributed to the histiocytic response. By immunohistochemistry, the foamy cells displayed immunoreactivity for lysozyme, alpha-1-antitrypsin, alpha-1-antichymotrypsin, and cathepsin D, providing additional support for their histiocytic derivation. To our knowledge, this is the first time that microparticles of cobalt-chromium and titanium that migrate from hip prostheses to pelvic lymph nodes have been shown to elicit a distinctive type of florid sinus histiocytosis. Pathologists should be aware of this characteristic foreign-body tissue response to avoid confusion with other types of sinus histiocytosis or with metastatic carcinoma.

Aged↗

Depression of liver metabolism and induction of cytokine release by diphtheria and tetanus toxoids and pertussis vaccines: role of Bordetella pertussis cells in toxicity.

A 24-h pretreatment of mice with diphtheria and tetanus toxoids and whole-cell pertussis vaccines depressed liver cytochrome P-450 and therefore prolonged hexobarbital-induced sleeping time in mice. The depression of liver drug metabolism by a cellular vaccine containing a mutated pertussis toxin was less marked than that induced by the wild-type vaccines, indicating that the mutated vaccine might have lower toxicity in this regard. The wild-type vaccines decreased microsomal P-450 levels by 50%, while the mutated whole-cell vaccine had a less marked effect (a decrease of 30%), paralleling the results obtained in sleeping time experiments. Furthermore, an acellular mutated vaccine did not affect liver drug metabolism, indicating a role of the whole bacterial cell in this side effect. All the cellular vaccines studied induced high serum interleukin-6 levels; on the other hand, the acellular mutated vaccine induced very low interleukin-6 levels, indicating that the whole bacterial cell is also important for interleukin-6 induction. All vaccines studied were very poor tumor necrosis factor inducers.

Animals↗

Polymerase chain reaction for rapid diagnosis of tuberculous meningitis in AIDS patients.

We used a test based on the polymerase chain reaction (PCR) for the detection of Mycobacterium tuberculosis DNA in 11 CSF samples from 10 HIV-seropositive patients in whom tuberculous meningitis was suspected. PCR was positive in nine samples from eight patients in whom clinical data, CSF findings, evidence of tuberculosis at an extraneural site, and response to antituberculous drug therapy supported the diagnosis, whereas cultures were positive in five of these nine samples and staining in only one. The PCR was negative in 14 CSF samples from the control group.

Acquired Immunodeficiency Syndrome↗

Mechanisms of interleukin-2-induced hydrothoraxy in mice: protective effect of endotoxin tolerance and dexamethasone and possible role of reactive oxygen intermediates.

Interleukin (IL)-2 is known to induce vascular leak syndrome (VLS), which was suggested to be mediated by immune system-derived cytokines, including tumor necrosis factor (TNF). To characterize the role of TNF in IL-2 toxicity in C3H/HeN mice, we used two approaches to downregulate TNF production in vivo: treatment with dexamethasone (DEX) and induction of endotoxin (lipopolysaccharide) (LPS) tolerance by a 4-day pretreatment with LPS (35 micrograms/mouse/day). Mice were then treated with IL-2 for 5 days (1.8 x 10(5) IU/mouse, twice daily). Both DEX and LPS tolerance blocked development of hydrothorax in IL-2-treated mice and inhibited TNF induction. DEX and LPS tolerance also ameliorated IL-2 toxicity in terms of decrease in food intake and inhibited the increase of the acute-phase protein, serum amyloid A (SAA). The IL-2 activation of splenic natural killer (NK) cell activity was also diminished by DEX and, to a lesser extent, by LPS-tolerance. Treatment with IL-2 also caused induction of the superoxide-generating enzyme xanthine oxidase (XO) in tissues and serum and induced bacterial translocation in the mesenteric lymph nodes (MLN). These data suggest that multiple mechanisms, including NK cell activity, cytokines, and reactive oxygen intermediates, might be important in the vascular toxicity of IL-2.

Animals↗

Role of xanthine oxidase and reactive oxygen intermediates in LPS- and TNF-induced pulmonary edema.

We studied the role of reactive oxygen intermediates (ROI) in lipopolysaccharide (LPS)-induced pulmonary edema. LPS treatment (600 micrograms/mouse, IP) was associated with a marked induction of the superoxide-generating enzyme xanthine oxidase (XO) in serum and lung. Pretreatment with the antioxidant N-acetylcysteine (NAC)--1 gm/kg orally, 45 minutes before LPS--or with the XO inhibitor allopurinol (AP)--50 mg/kg orally at -1 hour and +3 hours--was protective. On the other hand nonsteroidal antiinflammatory drugs (ibuprofen, indomethacin, and nordihydroguaiaretic acid) were ineffective. These data suggested that XO might be involved in the induction of pulmonary damage by LPS. However, treatment with the interferon inducer polyriboinosylic-polyribocytidylic acid, although inducing XO to the same extent as LPS, did not cause any pulmonary edema, indicating that XO is not sufficient for this toxicity of LPS. To define the possible role of cytokines, we studied the effect of direct administration of LPS (600 micrograms/mouse, IP), tumor necrosis factor (TNF, 2.5 or 50 micrograms/mouse, IV), interleukin-1 (IL-1 beta, 2.5 micrograms/mouse, IV), interferon-gamma (IFN-gamma, 2.5 micrograms/mouse, IV), or their combination at 2.5 micrograms each. In addition to LPS, only TNF at the highest dose induced pulmonary edema 24 hours later. LPS-induced pulmonary edema was partially inhibited by anti-IFN-gamma antibodies but not by anti-TNF antibodies, anti-IL-1 beta antibodies, or IL-1 receptor antagonist (IL-1Ra).

Acetylcysteine↗

Monocyte chemotactic protein-1 inhibits the induction of nitric oxide synthase in J774 cells.

We evaluated the effect of monocyte chemotactic protein-1 (MCP-1) on the induction of nitric oxide synthase activity in J774 cells. MCP-1 was able to inhibit the production of nitric oxide induced by LPS and IFN-gamma in a dose-dependent manner. Moreover, the inhibition was only achieved when the cells were pretreated with MCP-1. No inhibition was observed when MCP-1 was added after stimulation with LPS and IFN-gamma. These results demonstrate that MCP-1 is able to inhibit the induction of nitric oxide synthesis.

Amino Acid Oxidoreductases↗

Chlorpromazine inhibits both the constitutive nitric oxide synthase and the induction of nitric oxide synthase after LPS challenge.

The effects of chlorpromazine on either the activity of mouse brain nitric oxide synthase or the induction of lung nitric oxide synthase in mice and rats were studied. Chlorpromazine inhibited the nitric oxide synthase activity in mouse brain cytosol. This effect could be reversed by adding an excess of calmodulin. In addition, chlorpromazine was able to inhibit the induction of lung nitric oxide synthase, in both species, after LPS administration. Furthermore, chlorpromazine also inhibited arginase activity in mouse lung cytosol.

Amino Acid Oxidoreductases↗

Salivary duct carcinoma.

BACKGROUND: Salivary duct carcinoma (SDC) is a distinctive salivary gland neoplasm morphologically characterized by intraductal and infiltrating components. Most tumors occur in the major salivary glands and demonstrate a propensity for invasive growth with early regional and distant metastases. Therefore, SDC is regarded as a high-grade malignancy in the current classification of salivary gland neoplasms. METHODS: In an effort to identify clinically relevant prognostic features, we studied the clinicopathologic and immunohistochemical findings in 15 SDC, with ultrastructural evaluation of three tumors. RESULTS: Thirteen SDC occurred in the parotid gland, one in the Stensens duct, and one in the palate. Twelve patients were men (ratio of men to women = 4:1). Patients ranged in age from 39 to 81 years (mean = 59 years). Tumor size varied from 1.2 to 6.5 cm (mean = 3.1 cm). An intraductal component was identified in 10 of 14 primary SDC that made up 10% to 95% of the tumor. In three SDC a preexisting pleomorphic adenoma was identified. Immunohistochemical and electron microscopic evaluation showed the SDC to be composed entirely of ductal cells, and one tumor exhibited features of striated duct differentiation. CONCLUSIONS: SDC show a broader clinicopathologic spectrum than previously described. The tumor may arise in a pleomorphic adenoma. The proportion of intraductal and extraductal growth is variable and of prognostic significance. Although the majority of SDC behave in a high-grade fashion, those with a predominant intraductal component of greater than 90% (PID-SDC) and minimally invasive (< 8 mm) SDC in pleomorphic adenoma appear to have a more favorable prognosis.

Adenoma, Pleomorphic↗

Detection of Mycobacterium tuberculosis DNA in clinical samples by using a simple lysis method and polymerase chain reaction.

We have evaluated the polymerase chain reaction for detection of Mycobacterium tuberculosis in clinical samples from patients with tuberculous infection. Two simple methods for mycobacterial DNA release have been compared: sonication and lysis with nonionic detergents and proteinase K. The more effective method was the enzymatic technique. By using this protocol with 75 specimens we detected M. tuberculosis DNA in all of the samples, whereas only 48 and 71 samples were positive by acid-fast staining and culture, respectively.

Bacteriolysis↗

Properties of whole cell currents in isolated olfactory neurons from the chilean toad Caudiverbera caudiverbera.

Isolated olfactory neurons from the chilean toad Caudiverbera caudiverbera were found to possess a same set of currents. Outward currents, made of a delayed rectifier and a Ca(2+)-dependent component, were blocked by replacing K+ by Cs+ in the patch pipette, in the presence of millimolar concentrations of tetraethylammonium and 4-aminopyridine in the external solution. Inward currents were made of a transient and a maintained component. The transient was abolished in the absence of external Na+ and was blocked by tetrodotoxin, with an apparent dissociation constant (KDapp) of 25.4 +/- 0.3 nM. The maintained inward currents were suppressed on removing external Ca2+, could be carried also by Ba2+, and were selectively blocked by Cd2+ (KDapp = 3.2 +/- 1.3 microM). A variety of agents found to block the maintained Ca2+ inward currents, including Co2+ and Ni2+, at millimolar concentrations, and nifedipine, verapamil, amiloride, and the amiloride analogue benzamil, at micromolar concentrations, were also effective in either modifying the gating of, or in blocking, the transient inward currents.

Animals↗

Complex analyte-dependent and analyte-independent interferences with conjugated bilirubin in the enzymatic phenol-aminophenazone peroxidase (PAP) method for creatinine determination.

Although bilirubin interferes with the enzymatic assays for creatinine, neither a consensus of the degree of interference nor the mechanism has been established. Using multiple regression analysis, we demonstrate that the interference is negative and caused by both analyte-dependent and analyte-independent mechanisms. Furthermore, the correlative model includes terms non-linear with respect to creatinine. In the kinetic creatinine phenol-aminophenazone peroxidase method, there are analyte-dependent and analyte-independent mechanisms at work. The multivariate equation is: Crea' = 0.9879 Crea - 0.4524 Bili - 0.000828 Crea x Bili + 2.094 x 10(-7) Crea2 x Bili + 5.0 (Crea' = measured creatinine (mumol/l), Crea = true creatinine (mumol/l), and Bili = conjugated bilirubin (mumol/l)). The endpoint mode was affected less than the kinetic mode and exhibited different relationships in which two models describe the interference equally well. One is strictly analyte-dependent: Crea' = 0.9991 Crea - 0.00203 Crea x Bili + 2.390 x 10(-6) Crea2 x Bili - 1.464 x 10(-9) Crea3 x Bili + 3.261 x Bili + 3.261 x 10(-13) Crea4 x Bili - 9.9. The other is a complex combined analyte-dependent and analyte-independent: Crea' = 0.9834 Crea - 0.00680 Crea x Bili + 2.477 x 10(-7) Crea2 x Bili - 3.233 x 10(-7) Crea x Bili2 + 0.4652 Bili - 0.000458 Bili2 + 12.2. These models are valid for creatinine concentrations up to 2200 mumol/l (24.9 mg/dl) and bilirubin up to 660 mumol/l (38.6 mg/dl). The interference increases with increments of either bilirubin or creatinine. In addition, we found that unconjugated bilirubin interferes differently from conjugated bilirubin in degree and mechanism. Model building, contour plots, surface plots, and possible mechanisms are discussed. We propose multiple regression analysis as the proper way to evaluate interferences because analyte-dependence can be easily missed by simple regression analysis. True creatinine concentrations can be estimated despite the interference from conjugated bilirubin. Other phenol-aminophenazone peroxidase methods may be similarly affected.

Aminopyrine↗

Pharmacological activities of chlorpromazine involved in the inhibition of tumour necrosis factor production in vivo in mice.

Chlorpromazine (CPZ) was shown to inhibit tumour necrosis factor (TNF) production in vivo. Several drugs sharing one of the various pharmacological activities of CPZ were tested in endotoxin-treated mice. It was found that alpha-blockers (prazosin, idazoxan, phenoxybenzamine), antiserotoninergics (methysergide, methergoline) and antihistamine (chlorpheniramine, promethazine) also inhibited TNF production indicating that the effectiveness of CPZ in protecting from endotoxin shock is due to its multiple pharmacological activities.

Adrenergic alpha-Antagonists↗

K(+)-channel blockers restore synaptic plasticity in the neuromuscular junction of dunce, a Drosophila learning and memory mutant.

The effects of K(+)-channel blockers on synaptic transmission in dunce (dnc), a Drosophila learning and memory mutant, were investigated. Larvae dnc mutants lack facilitation and post-tetanic potentiation (PTP) at their motor end-plates; dnc mutants are also deficient in a form of phosphodiesterase, and exhibit abnormally high levels of cyclic adenosine 3',5'-monophosphate (cAMP). A two-microelectrode voltage-clamp was used to record end-plate currents and spontaneous end-plate currents from longitudinal ventrolateral third-instar larval muscle. The K(+)-channel blockers 3,4-diaminopyridine (3,4-DAP) and tetraethylammonium (TEA), at micromolar concentrations, caused a reversible decrease in end-plate current amplitudes both in wild-type and mutant end-plates. In the presence of blockers, a period of high-frequency stimulation (tetanus) of the nerve gave way to a transient increase in the end-plate currents of dnc mutants resembling facilitation and PTP in normal end-plates; 3,4-DAP and TEA also restored facilitation and PTP in normal end-plates after incubation with a non-hydrolysable analogue of cAMP (8Br-cAMP). It is suggested that a specific K+ conductance might be relevant to the lack of synaptic plasticity at the dnc neuromuscular synapses.

4-Aminopyridine↗

Low predictive value of polymerase chain reaction for diagnosis of cytomegalovirus disease in liver transplant recipients.

The polymerase chain reaction (PCR) and viral culture techniques were prospectively compared for the detection of cytomegalovirus (CMV) in blood samples from 24 liver transplant recipients. Nine patients had one or more episodes of viremia, seven of which were clinically symptomatic infections. All samples in which CMV was isolated by culture were positive by the PCR. However, the PCR result was also positive for one or more samples from 11 patients who never developed CMV-related symptoms. Although the PCR is a very sensitive technique for CMV detection in blood samples from liver transplant recipients, it is not useful as a marker of symptomatic CMV disease.

Cytomegalovirus↗

[Reproductive cycle of the pocket gophers Orthogeomys cherriei (Rodentia: Geomyidae) in Costa Rica].

Pocket gophers (Orthogemys cherriei) is a pest in agriculture in Limón, Costa Rica; 232 animals were trapped in several farms. They reproduce continuously throughout the year. Adults of both sexes are found in reproductive condition at any time. The females produce at least 2 litters per year (1-4 newborns each). There is no correlation between position of testes and production of sperm. The position of the testes is not a reliable factor to establish the reproductive condition in males. There is a correlation between length of os penis (baculum) and length of the testes, irrespectively of its reproductive condition. These pocket gophers disperse above-ground.

Animals↗

Expression of cloned bovine adrenal rhodanese.

A cDNA for the enzyme rhodanese (thiosulfate:cyanide sulfurtransferase, EC 2.8.1.1) has been cloned from a bovine adrenal library. An initiator methionine codon precedes the amino-terminal amino acid found in the isolated protein. Rhodanese is synthesized in the cytoplasm and transferred to the mitochondrial matrix. Thus, any amino-terminal sequence required for organelle import is retained in the mature protein. Furthermore, the DNA sequence shows that there are three additional amino acids, Gly-Lys-Ala, at the carboxyl terminus that are not found by protein sequencing. Additionally, comparison of the published amino acid sequence with that encoded by the open reading frame revealed three differences in the amino acid sequence. Comparison of the bovine and chicken liver sequences shows an overall level of 70% sequence homology, but there is complete identity of all residues that have been implicated in the function of the enzyme. When two mammalian cells, cos-7 and 293 cells, were transiently transfected with a plasmid containing the rhodanese coding region, rhodanese activity in lysates increased approximately 20-fold. Fluorograms of denaturing polyacrylamide gels detected a large increase in a polypeptide that co-migrated with the native protein and reacted with anti-rhodanese antibodies. Nondenaturing gels showed two active species that co-migrated with the two major electrophoretic forms purified by current procedures. Escherichia coli, transformed with a plasmid containing the rhodanese coding region, showed a 15-fold increase in rhodanese activity over baseline values. When the E. coli recombinant protein was analyzed on a nondenaturing gel, only one species was observed that co-electrophoresed with the more electropositive variant seen in purified bovine liver rhodanese. This single variant could be converted by carboxypeptidase B digestion to a form of the enzyme that co-migrated with the more electronegative species isolated from bovine liver. Thus, two major, enzymatically active electrophoretic variants, commonly observed in mammalian cells, can be accounted for by carboxyl-terminal processing without recourse to other post-translational modifications.

Adrenal Glands↗