Search PubMed⌕ Search

Biomedical subjects

R Delgado

Publications and source records attributed to R Delgado.

At least 73 records · Page 4Linked to original sources

Outward currents in Drosophila larval neurons: dunce lacks a maintained outward current component downregulated by cAMP.

Outward current modulation by cAMP was investigated in wild type (wt) and dunce (dnc) Drosophila larval neurons. dnc is deficient in a cAMP phosphodiesterase and has altered memory. Outward current modulation by cAMP was investigated by acute or chronic exposure to cAMP analogs. The analysis included a scrutiny of outward current modulation by cAMP in neurons from the mushroom bodies (mrb). In Drosophila, the mrb are the centers of olfactory acquisition and retention. Based on outward current patterns, neurons were classified into four types. Downmodulation of outward currents induced by acute application of cAMP analogs was reversible and found only in type I and type IV neurons. In the general wt neuron population, approximately half of neurons exhibited cAMP-modulated, 4-aminopyridine (4-AP)-sensitive currents. On the other hand, a significantly larger fraction of mrb neurons in wt (70%) was endowed with cAMP-modulated, 4-AP-sensitive currents. Only 30% of the dnc neurons displayed outward currents modulated by cAMP. The deficit of cAMP-modulated outward currents was most severe in neurons derived from the mrb of dnc individuals. Only 4% of the mrb neurons of dnc were cAMP-modulated. The dnc defect can be induced by chronic exposure of wt neurons to cAMP analogs. These results document for the first time a well defined electrophysiological neuron phenotype in correlation with the dnc defect. Moreover, this study demonstrates that in dnc mutants such a deficiency affects most severely neurons in brain centers of acquisition and retention.

Animals↗

Distinct cellular interactions of secreted and transmembrane Ebola virus glycoproteins.

The mechanisms by which Ebola virus evades detection and infects cells to cause hemorrhagic fever have not been defined, though its glycoprotein, synthesized in either a secreted or transmembrane form, is likely involved. Here the secreted glycoprotein was found to interact with neutrophils through CD16b, the neutrophil-specific form of the Fc gamma receptor III, whereas the transmembrane glycoprotein was found to interact with endothelial cells but not neutrophils. A murine retroviral vector pseudotyped with the transmembrane glycoprotein preferentially infected endothelial cells. Thus, the secreted glycoprotein inhibits early neutrophil activation, which likely affects the host response to infection, whereas binding of the transmembrane glycoprotein to endothelial cells may contribute to the hemorrhagic symptoms of this disease.

Cell Line↗

Melanocortin peptides inhibit production of proinflammatory cytokines and nitric oxide by activated microglia.

Inflammatory processes contribute to neurodegenerative disease, stroke, encephalitis, and other central nervous system (CNS) disorders. Activated microglia are a source of cytokines and other inflammatory agents within the CNS and it is therefore important to control glial function in order to preserve neural cells. Melanocortin peptides are pro-opiomelanocortin-derived amino acid sequences that include alpha-melanocyte-stimulating hormone (alpha-MSH) and adrenocorticotropic hormone (ACTH). These peptides have potent and broad anti-inflammatory effects. We tested effects of alpha-MSH (1-13), alpha-MSH (11-13), and ACTH (1-24) on production of tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and nitric oxide (NO) in a cultured murine microglial cell line (N9) stimulated with lipopolysaccharide (LPS) plus interferon gamma (IFN-gamma). Melanocortin peptides inhibited production of these cytokines and NO in a concentration-related fashion, probably by increasing intracellular cAMP. When stimulated with LPS + IFN-gamma, microglia increased release of alpha-MSH. Production of TNF-alpha, IL-6, and NO was greater in activated microglia after innmunoneutralization of endogenous alpha-MSH. The results suggest that alpha-MSH is an autocrine factor in microglia. Because melanocortin peptides inhibit production of pro-inflammatory mediators by activated microglia they might be useful in treatment of inflammatory/degenerative brain disorders.

Adrenocorticotropic Hormone↗

Clear cell adenocarcinoma and nephrogenic adenoma of the urethra and urinary bladder: a histopathologic and immunohistochemical comparison.

Because of histological similarities between nephrogenic adenomas and clear cell adenocarcinomas of the urinary tract, there is the potential for diagnostic confusion between these two entities. The histopathologic features of 13 nephrogenic adenomas and five clear cell adenocarcinomas of the urethra and urinary bladder are compared in this report, and detailed immunohistochemical staining profiles are provided for these tumors. Only 2 of the 13 nephrogenic adenomas contained clear cells, and these constituted less than 10% of the lesions. In contrast, four of the five clear cell adenocarcinomas contained prominent areas with clear cells. Nephrogenic adenomas generally showed only mild cytologic atypia, whereas four of the five clear cell adenocarcinomas showed severe atypia. A single mitotic figure was identified in only two of the nephrogenic adenomas, whereas the mitotic rate in the clear cell adenocarcinomas ranged from 2 to 14 per 10 high-power fields. None of the nephrogenic adenomas showed evidence of necrosis, but focal necrosis was noted in four of the five clear cell adenocarcinomas. In general, the nephrogenic adenomas and clear cell adenocarcinomas showed negative to weak staining with CK903 but strong staining with AE1, AE3, and Cam 5.2. Variable staining was observed with Brst-3 and antibodies to S-100, CEA (monoclonal and polyclonal), LeuM-1, and CA19.9. Nephrogenic adenomas and clear cell adenocarcinomas were all negative for prostate-specific acid phosphatase (PSAP), prostate-specific antigen (PSA), and estrogen and progesterone receptors (except for two nephrogenic adenomas, which showed only focal weak staining for estrogen receptor). Neither bcl-2 nor c-erbB-2 staining was able to discriminate between the tumors. However, strong staining for p53 was noted in each clear cell adenocarcinoma and in none of the nephrogenic adenomas. MIB-1 positivity in nephrogenic adenomas ranged from 0 to 13 (average of 5.5) per 200 cells, whereas the positive range for clear cell adenocarcinomas was 33 to 70 (average of 47) per 200 cells. In summary, histopathologic features that favor clear cell adenocarcinoma over nephrogenic adenoma include a predominance of clear cells, severe cytological atypia, high mitotic rate, necrosis, high MIB-1 positivity, and strong staining for p53.

Adenocarcinoma, Clear Cell↗

Synaptic defects and compensatory regulation of inositol metabolism in inositol polyphosphate 1-phosphatase mutants.

Phosphoinositides function as important second messengers in a wide range of cellular processes. Inositol polyphosphate 1-phosphatase (IPP) is an enzyme essential for the hydrolysis of the 1-phosphate from either Ins(1,4)P2 or Ins(1,3,4)P3. This enzyme is Li+ sensitive, and is one of the proposed targets of Li+ therapy in manic-depressive illness. Drosophila ipp mutants accumulate IP2 in their system and are incapable of metabolizing exogenous Ins(1,4)P2. Notably, ipp mutants demonstrate compensatory upregulation of an alternative branch in the inositol-phosphate metabolism tree, thus providing a means of ensuring continued availability of inositol. We demonstrate that ipp mutants have a defect in synaptic transmission resulting from a dramatic increase in the probability of vesicle release at larval neuromuscular junctions. We also show that Li+ phenocopies this effect in wild-type synapses. Together, these results support a role for phosphoinositides in synaptic vesicle function in vivo and mechanistically question the "lithium hypothesis."

Animals↗

Biomineralization of carbonates by Halomonas eurihalina in solid and liquid media with different salinities: crystal formation sequence.

Carbonate precipitation by 20 strains of the moderately halophilic species Halomonas eurihalina in both solid and liquid media was studied. The influence of salinity and temperature on the quantity and type of crystals precipitated was also investigated. Some strains of H. eurihalina formed crystals in all conditions tested. The mineral phases precipitated were magnesium calcite, aragonite and monohydrocalcite in variable proportions depending on various factors such as the type of growth medium employed and its salinity. Scanning electron microscopy and X-ray dispersive energy microanalysis were used to investigate the crystal formation sequence. The process of biolith formation was sequential. It started with chains or filaments of bacteria, giving way to discs which finally produced spherical forms of approximately 50 microns in diameter. We suggest a mechanism of carbonate crystal formation by H. eurihalina.

Carbonates↗

Improvement of reversible ischemia in severe post-transplantation coronary artery disease.

Coronary artery disease is a major cause of morbidity and mortality in patients who have undergone heart transplantation. Patients are often asymptomatic during the onset of the disease, and managing the disease is difficult. This report describes the case of a patient with post-transplantation coronary artery disease who, despite the severe, progressive appearance of the disease on angiographic examination, showed evidence of autorevascularization and collateralization.

Cardiac Catheterization↗

Testicular Sertoli cell tumor with a heterologous sarcomatous component: immunohistochemical assessment of Sertoli cell differentiation.

OBJECTIVE: Immunohistochemical staining is reported to be useful in distinguishing ovarian Sertoli-stromal cell tumors from carcinosarcomas. To assess Sertoli cell differentiation in a rare malignant biphasic testicular tumor, we compared the immunophenotypic profile of the tumor with that of Sertoli cell nodules and adenomas and mullerian carcinosarcomas. DESIGN: Immunohistochemical staining was performed on 6 testes (4 with hyperplastic Sertoli cell nodules, 2 with Sertoli cell adenomas) and 7 carcinosarcomas (6 involving the uterus, 1 involving the uterus and ovary) using primary monoclonal antibodies AE1/AE3, CAM 5.2, CA 19.9, and antibodies directed against epithelial membrane antigen, carcinoembryonic antigen (monoclonal and polyclonal), S100, placental alkaline phosphatase, and inhibin. These staining results were compared with those of the index case. RESULTS: All testes showed positive staining for inhibin and vimentin in the Sertoli cells of the nodules and adenomas. One Sertoli cell nodule showed focal staining with AE1/AE3 and CAM 5.2. Both adenomas showed focal positive staining for S100. All nodules and adenomas were negative for epithelial membrane antigen, monoclonal and polyclonal carcinoembryonic antigen, CA 19.9, and placental alkaline phosphatase. In contrast, the carcinomatous areas of the carcinosarcomas were all negative for inhibin but exhibited positive staining for AE1/AE3, CAM 5.2, and epithelial membrane antigen. The carcinosarcomas showed variable expression of vimentin, S100, carcinoembryonic antigen, CA 19.9, and placental alkaline phosphatase. The epithelial component of the tumor from the index case showed strong diffuse staining for inhibin and vimentin and only very faint focal staining with AE1/AE3 and CAM 5.2. The epithelial component was negative for epithelial membrane antigen, monoclonal and polyclonal carcinoembryonic antigen, S100, CA 19.9, and placental alkaline phosphatase. CONCLUSIONS: The immunohistochemical findings in the index case support the diagnosis of Sertoli cell tumor with a heterologous sarcomatous component over carcinosarcoma. Inhibin seems to be the best single marker for Sertoli cell differentiation. To our knowledge, only 1 other case of this rare testicular tumor has been reported in the literature.

Aged↗

Linked pacing after heterotopic heart transplantation with concurrent left ventricular reduction of the native heart.

A 30-year-old man with dilated cardiomyopathy underwent heterotopic heart transplantation, concurrently with surgical reduction of the native left ventricle, a mitral valvuloplasty, and an apical thrombectomy. Postoperatively, the patient had hemodynamic instability that was refractory to conventional medical therapy. Temporary sequential pacing of the 2 hearts was used to induce timed counterpulsation, which resulted in marked hemodynamic improvement. To the best of our knowledge, this case involves the 1st report in the English-language literature of clinical usage of paced, linked counter-pulsation to treat acute hemodynamic compromise early after heterotopic heart transplantation.

Adult↗

Role of O6-methylguanine-DNA methyltransferase in the resistance of pancreatic tumors to DNA alkylating agents.

Pancreatic adenocarcinomas rarely respond to radiation or chemotherapy, indicating that a large percentage of these tumors possess complex mechanisms of resistance. The failure of alkylating agents, such as carmustine [1,3-bis(2-chloroethyl)-1-nitrosourea; BCNU], lomustine [1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea; CCNU], and streptozotocin, to yield consistent therapeutic results further suggests that one of these mechanisms may be the high expression of O6-methylguanine-DNA methyltransferase (MGMT). All 12 human pancreatic ductal adenocarcinomas assayed for MGMT activity showed unusually high levels, implying that these malignancies are efficient in repairing genotoxic O6-alkylguanine lesions induced by methylating (streptozotocin) and 2-chloroethylating (BCNU and CCNU) chemotherapeutic genotoxic agents. Immunohistochemical analysis of an additional 15 pancreatic tumors showed that high levels of MGMT protein reside in the nucleus and the cytoplasm of malignant cells. Both nuclear and cytoplasmic staining were absent in hyperplastic duct epithelium, but staining was invariably present in moderate to highly dysplastic foci and especially strong in invasive components of the tumor. With the exception of lymphocytes that were MGMT positive, acinar, ductal, and islet cells did not stain for MGMT in histologically normal pancreata. These data indicate that MGMT activity is up-regulated in dysplastic epithelium, and its expression increases during tumor progression, reaching the highest levels in the invasive components of the tumor. Resistance of pancreatic tumor cells to alkylating agents was verified with four pancreatic tumor cell lines. CAPAN-2, CFPAC-1, PANC-1, and MIAPaCa-2, having MGMT levels of 1800, 987, 700, and 880 fmol/mg protein, respectively, were resistant to BCNU, but their resistance declined sharply following pretreatment with the MGMT inhibitor O6-benzylguanine (O6-BG). On the other hand, PANC-1 and MIAPaCa-2 could not be eradicated with N-methylnitrosourea (MNU) at concentrations as high as 2 mM, even when pretreated with O6-BG. These two lines were shown to be modified genetically in microsatellite sequences by MNU and are believed to have a defective mismatch repair system, which may explain their resistance to methylating agents. Failure of pancreatic tumors to respond to nitrosoureas is related to high levels of MGMT expression and in some cases to genomic instability. However, these tumors can be sensitized to chloroethylating drugs and eradicated following the elimination of MGMT activity by O6-BG or homologous MGMT inhibitors.

Adenocarcinoma↗

Signet-ring sinus histiocytosis: a reactive disorder that mimics metastatic adenocarcinoma.

BACKGROUND: Signet-ring sinus histiocytosis is a rare and distinctive reactive disorder recently observed in the axillary lymph nodes of patients with breast carcinoma. This form of sinus histiocytosis closely resembles and can easily be confused with metastatic adenocarcinoma. METHODS: To determine the incidence of this reactive process in lymph nodes from different anatomic sites, broaden its morphologic spectrum, and discuss the differential diagnosis, the authors examined lymph nodes from 316 radical prostatectomy specimens, 184 modified radical mastectomy specimens, 108 colectomy specimens, 57 gastrectomy specimens, and 27 radical hysterectomy specimens. These surgical procedures were performed to treat carcinoma of the prostate, breast, colon, stomach, and uterine cervix, respectively. A total of 9741 lymph nodes were histologically examined. The lymph nodes containing sinus signet-ring cells were stained with mucicarmine, Alcian blue, and periodic acid-Schiff stains (PAS). Immunostains for epithelial, lymphoid, and histiocytic markers were also performed. In two cases, tissue was retrieved from the paraffin block and subsequently processed for electron microscopic examination. RESULTS: Only 4 of 316 radical prostatectomy specimens (1.2%) and 2 of 184 axillary dissections (1.08%) contained lymph nodes with signet-ring sinus histiocytosis. Of 9741 lymph nodes reviewed, 37 (24 pelvic and 13 axillary lymph nodes) had signet-ring sinus histiocytosis, for an incidence of 0.38%. Microscopically, the signet-ring histiocytes lacked nuclear atypia and were mucin negative. In two cases, clusters of histiocytes with rounded, eosinophilic, diastase resistant, PAS positive cytoplasmic globules were observed. Both types of signet-ring cells showed reactivity for histiocytic markers and were negative for cytokeratin and lymphoid markers. By electron microscopy, most histiocytes were shown to have a large empty vacuole that displaced the nucleus. Granular material was observed in some of the vacuoles. Some histiocytes exhibited a rounded cytoplasmic body composed of central electron dense, granular material and a rim of microfibrils. No lipid droplets were identified. CONCLUSIONS: Signet-ring sinus histiocytosis is a rare and distinctive reactive disorder found incidentally in the pelvic and axillary lymph nodes of patients with carcinoma of the prostate and breast, respectively. Although this histiocytic reaction mimics metastatic adenocarcinoma and signet-ring cell lymphoma, it can be identified by careful cytologic analysis together with positive reactivity for histiocytic markers, negative mucin stains, and lack of reactivity for epithelial and lymphoid markers. The etiology and pathogenesis of this unusual form of sinus histiocytosis remains unclear.

Adenocarcinoma↗

Role of epicardial pacing wire cultures in the diagnosis of poststernotomy mediastinitis.

Mediastinitis after cardiac surgery is difficult to diagnose in many cases. The transitory epicardial pacing wires used after surgery are placed in the mediastinum, so the culture of these wires could be useful for the diagnosis of this disease. To test this hypothesis, we routinely cultured the epicardial pacing wires of 565 patients undergoing extracorporeal circulation. Wires were removed on the 7th to 9th postoperative day under sterile conditions and were cultured with routine techniques used for the culture of venous catheters. Mediastinitis developed in 16 patients, and Staphylococcus aureus was the most common pathogen (81.25%). We had 103 positive and 462 negative cultures. There were 458 true-negative, 12 true-positive, 91 false-positive and 4 false-negative results. For mediastinitis in general, epicardial pacing wire culture has a sensitivity of 75%, specificity of 83.4%, positive predictive value of 11.6%, and negative predictive value of 99.1%. For Staphylococcus aureus mediastinitis, epicardial pacing wire culture has a sensitivity of 84.6%, specificity of 95.8%, positive predictive value of 32.3%, and negative predictive value of 99.6%. We conclude that a sterile culture of the epicardial pacing wires strongly contradicts a diagnosis of postsurgical mediastinitis.

Cardiac Surgical Procedures↗

Basal cell carcinoma of trunk and extremities.

BACKGROUND: Basal cell carcinoma is the most common malignancy in Caucasians. Information about basal cell carcinoma in the Mexican population is scarce. OBJECTIVE: To determine the epidemiologic and clinical characteristics and treatment results of basal cell carcinoma located on the trunk and extremities of patients seen at the Instituto Nacional de Cancerología of Mexico. METHODS: A retrospective study was performed of patients with confirmed diagnosis of basal cell carcinoma located on the trunk and extremities seen at the Instituto Nacional de Cancerología of Mexico between 1966 and 1993. RESULTS: Ninety-one patients with basal cell carcinoma located on the trunk and extremities were found (6% of all patients with diagnosis of basal cell carcinoma). The median age was 64 years; 52% of the patients were women and 48% were men. A total of 119 basal cell carcinomas at these locations were diagnosed. The size of the skin tumor ranged from 0.3 to 22 cm (mean, 3.9 cm). Treatment results were evaluated in 62 patients (follow-up ranged from 24 to 240 months; mean, 80 months). Overall tumor control was accomplished in 95% of cases. Three patients died as a result of basal cell carcinoma. CONCLUSIONS: Basal cell carcinoma in the Mexican population is not as infrequent as previously thought, although it is less commonly located on the trunk and extremities than in Caucasians.

Adult↗

Low grade salivary duct carcinoma. A distinctive variant with a low grade histology and a predominant intraductal growth pattern.

BACKGROUND: Salivary duct carcinoma (SDC) has been established as a morphologically distinct and highly aggressive (HG) malignancy of the major salivary glands. However, a low grade (LG) or intermediate grade salivary duct neoplasm has not been described. METHODS: We report the clinicopathologic findings of 10 cases believed to represent the (LG) counterpart of SDC. Immunoperoxidase stains were performed on five cases, and electron microscopy on three. RESULTS: All of the tumors occurred in adult patients with no sex predilection, and presented as slow growing parotid gland lesions. Four cases involved the superficial lobe, one the deep lobe, and one arose within an intraparotid lymph node. The exact location of the tumor within the parotid gland was not stated in four cases. The size of the tumors ranged from 0.7 to 4 cm in greatest dimension, with most measuring between 1 and 2 cm. The gross appearance was focally to predominantly cystic. Microscopically, the tumors were characterized by intraductal proliferative lesions exhibiting three main patterns: (1) cystic ducts with micropapillary, tufted, and plaque-like intraluminal projections; (2) ducts distended by a solid or pseudocribriform (fenestrated) cellular proliferation, with varied cystic dilatation; and (3) ducts exhibiting architectural atypia. The three patterns coexisted and merged in most tumors, in varying proportions. All tumors shared bland to LG cytologic features, with the exception of one that had focal high-grade cytologic ductal atypia. Despite gross circumscription, there was microscopic multifocality, and in one case, stromal invasion. By immunohistochemistry, the neoplastic cells expressed the conventional ductal and glandular epithelial cell markers in addition to strong positivity for S-100 with coexpression for CK-903. Electron microscopy confirmed the ductal phenotype of the tumors and supported an in situ process evidenced by the presence of native myoepithelial cells. Nine patients underwent total parotidectomy and one superficial parotidectomy. One patient received radiation therapy following total parotidectomy. Follow-up for 6 cases ranged from 2 to 12 years and revealed no evidence of disease. CONCLUSIONS: LG-SDC represents the LG end of the spectrum of salivary duct malignant neoplasms and exhibits differentiation towards an intercalated duct-like cell phenotype. Its relationship to HG-SDC should be further explored.

Adult↗

Effect of advanced glycosylation end products on the induction of nitric oxide synthase in murine macrophages.

We studied the role of advanced glycosylation end products on the induction of nitric oxide synthase in peritoneal mouse macrophages previously exposed to modified BSA. A dose-dependent increment in the nitric oxide production induced by LPS and IFN-gamma was observed when cell cultures were pretreated with modified BSA for 48 hours. In addition, the up regulation of nitric oxide production was also time-dependent, being maximal at 24-48 hours. Experiments carried out in the presence of neutralizing antibodies to IL-1 and TNF-alpha, suggested that up regulation was not due to the capacity of modified BSA to induce both proinflammatory signals. The up regulation of nitric oxide production was paralleled with an increase in iNOS mRNA.

Animals↗