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Biomedical subjects

M Delgado

Publications and source records attributed to M Delgado.

At least 109 records · Page 6Linked to original sources

Probable effect of photoperiod on seasonal variation in the nuclear volume of the adrenal cortex of viscacha (Lagostomus maximus maximus).

The neuroendocrine system regulates several organic functions such as reproduction, metabolism and adaptation to the environment. This system shows seasonal changes linked to the environment. The experimental model used in the present study was Lagostomus maximus maximus (viscacha). The reproduction of males of this species is photoperiod dependent. Twenty-four adult male viscachas were captured in their habitat at different times during one year. The adrenal glands were processed for light microscopy. Serial cuts were stained with hematoxylin-eosin for the morphometric study, and 100 nuclei of each zone of the adrenal cortex were counted per animal. Data were analyzed statistically by ANOVA and the Tukey test. The cells of the glomerulosa zone are arranged in a tube-shaped structure. The fasciculata zone has large cells with central nuclei and clearly visible nucleoli and with a vacuolar cytoplasm. In the reticularis zone there are two of types of cells, one with a nucleus of fine chromatin and a clearly visible nucleolus and the other with nuclear pycnosis. Morphometric analysis showed maximum nuclear volumes during the February-March period with values of 133 +/- 7.3 microm3 for the glomerulosa, 286.4 +/- 14.72 microm3 for the fasciculata, and 126.3 +/- 9.49 microm3 for the reticularis. Minimum nuclear volumes were observed in August with values of 88.24 +/- 9.9 microm3 for the glomerulosa, 163.7 +/- 7.78 microm3 for the fasciculata and 64.58 +/- 4.53 microm3 for the reticularis. The short winter photoperiod to which viscacha is subjected could inhibit the adrenal cortex through a melatonin increase which reduces the nuclear volume as well as the cellular activity.

Adrenal Cortex↗

[Scintigraphy with 99MTc-HMPAO labeled leukocytes and computed tomography in the diagnosis of vascular graft infection. A comparative study].

The purpose of this work was to compare the results obtained with a scitigraphy using 99mTc-HMPAO labeled leukocyte and a computed tomography (CT) in the diagnosis of vascular graft infection (VGI). We carried out 22 studies with both scintigraphy and CT in 20 patients with vascular grafts with VGI suspicion. One patient had two grafts, thus a total of 23 grafts were analyzed. In addition, 6 control studies were performed. The persistent increase in leukocyte uptake in the graft area was considered as evidence of VGI and the scintigraphy with HMPAO-99mTc labeled leukocytes. For the CT, the presence of perigraft fluid and/or gas collection in the graft bed was also considered to be evidence of VGI. The total number of VGI was 12. The VGI diagnosis was confirmed by culture in all cases. The sensitivity and specificity of the scintigraphy in the diagnosis of VGI was 100%, while the CT has a sensitivity of 58% and specificity of 91%. Five grafts presented pseudoaneurysm in distal aorto-bifemoral graft anastomosis. All theses cases were detected with CT and only one patient with pseudoaneurysms showed scintigraphic evidence of VGI. In addition, both techniques detected two soft tissue infections associated with cutaneous fistulae, one case of abdominal abscess and another of acute diverticulitis. The scintigraphy was also pathologic in one infection of the surgical wound while that the CT was negative. In conclusion, although both techniques are useful to evaluate patients with suspicion of VGI, the scintigraphy with 99m-Tc-HMPAO labeled leukocytes has been shown to be more sensitive than the CT in the assessment of patients with VGI suspicion.

Aged↗

[Hypothyroidism in patients treated for laryngeal cancer: preliminary results].

OBJECTIVE: The reported incidence of hypothyroidism following surgery and/or irradiation for laryngeal cancer varies widely and the condition often is misdiagnosed. This study examines the incidence of thyroid dysfunction in patients with laryngeal cancer. MATERIAL AND METHODS: Thyroid function tests were carried out in 75 patients with stage III and IV laryngeal carcinoma who were treated in our center with surgery (13 cases), radiotherapy (13 cases), or surgery and radiotherapy (49 cases) at least 18 months earlier. The clinical and histological variables recorded included T4 and TSH concentrations. Univariate and multivariate analysis was carried out with the BMDP program from UCLA (1995 version) to examine the relationship between hypothyroidism and clinical and pathological factors. RESULTS: Twenty-nine patients (38.6%) had high TSH or low T4 concentrations and were diagnosed as having hypothyroidism. Hypothyroidism was significantly related with date of surgery (before 1993) and the treatment used on the neck. Thyroid function was rarely affected in patients who underwent functional neck dissection, but radical neck dissection and irradiation of the neck always were followed by hypothyroidism. CONCLUSIONS: Thyroid testing should be performed routinely in the follow-up of laryngeal cancer. Many psychological symptoms attributed to total laryngectomy may be due to hypothyroidism, an easily treated condition.

Carcinoma, Squamous Cell↗

Identification of laminin alpha1 and beta1 chain peptides active for endothelial cell adhesion, tube formation, and aortic sprouting.

Laminin-1 is a basement membrane glycoprotein that promotes several biological activities including cell attachment, tumor metastasis, and angiogenesis. Angiogenesis plays an important role in tissue formation, reproduction, wound healing, and several pathological conditions. In this study, we screened 405 synthetic peptides from the alpha1 and beta1 chains to identify potential sites on laminin-1 active with endothelial cells. Peptides were initially screened by testing both endothelial cell adhesion to peptide-coated wells and tube formation on Matrigel in the presence of soluble peptide. Twenty active peptides were identified in these screens. A secondary screen using the rat aortic ring sprouting assay identified 13 of the 20 peptides that stimulated endothelial sprouting. Several of these active peptides were also found to stimulate human umbilical vein endothelial cell migration in Boyden chamber assays. Differences in the amount of peptide needed for the response and in the resultant morphologies/responses were observed between the peptides in all of the assays. Our results suggest that several active domains on laminin-1 may play important roles in stimulating different steps in angiogenesis.

Amino Acid Sequence↗

Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide inhibit tumor necrosis factor alpha transcriptional activation by regulating nuclear factor-kB and cAMP response element-binding protein/c-Jun.

Tumor necrosis factor alpha (TNFalpha), an early cytokine produced by activated macrophages, plays an essential role in normal and pathological inflammatory reactions. The excessive production of TNFalpha is prevented by the so-called "macrophage-deactivating factors." This study examines the role of two structurally related neuropeptides, the vasoactive intestinal peptide (VIP) and the pituitary adenylate cyclase-activating peptide (PACAP), as inhibitors of TNFalpha. Both VIP and PACAP inhibit TNFalpha production from lipopolysaccharide-stimulated RAW 246.7 cells in a dose- and time-dependent manner. Although the activated cells express mRNA for all three VIP/PACAP receptors, agonist and antagonist studies indicate that the major receptor involved is VIP1R. VIP/PACAP inhibit TNFalpha gene expression by affecting both NF-kB binding and the composition of the cAMP responsive element binding complex (CREB/c-Jun). Two transduction pathways, a cAMP-dependent and a cAMP-independent pathway, are involved in the inhibition of TNFalpha gene expression and appear to differentially regulate the transcriptional factors involved. Because TNFalpha plays a central role in various inflammatory diseases such as endotoxic shock, multiple sclerosis, cerebral malaria, and various autoimmune conditions, the down-regulatory effect of VIP/PACAP may have a significant therapeutic potential.

Animals↗

VIP and PACAP enhance IL-6 release and mRNA levels in resting peritoneal macrophages: in vitro and in vivo studies.

Vasoactive intestinal peptide (VIP), a neuropeptide produced by lymphocytes has been previously reported to modulate cytokine expression in T lymphocytes. In this study, we investigated the effects of VIP and of the structurally related neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP38) on the production of IL-6 in unstimulated murine peritoneal macrophages. Both neuropeptides stimulate rapidly, specifically, and similarly the production of IL-6, exerting their action through two different receptor/signal transduction systems, i.e., primarily through the binding to VIP1/PACAP receptor followed by adenylate cyclase activation, and partially through the activation of protein kinase C following binding to PACAP-R. VIP and PACAP38 regulate the production of IL-6 at a transcriptional level, affecting the de novo synthesis of this cytokine. The stimulatory in vitro effect correlates with the stimulation of IL-6 expression and release in vivo. These studies suggest that VIP/PACAP play a role in immune system homeostasis, participating in the intricate cytokine network and controlling local immune responses. In addition, the understanding of the factors that regulate the expression and release of IL-6 by macrophages is important for the elucidation of the role of IL-6 in health and disease.

Animals↗

Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide modulate endotoxin-induced IL-6 production by murine peritoneal macrophages.

Vasoactive intestinal peptide (VIP) is a neuropeptide synthesized by immune cells that can modulate several immune aspects, including the function of cells involved in the inflammatory response, such as macrophages and monocytes. Production and release of cytokines by activated mononuclear phagocytes is an important event in the pathogenesis of ischemia-reperfusion injury. VIP has been shown to attenuate the deleterious consequences of this pathologic phenomenon. We have investigated the effects of VIP and PACAP38 on the production of interleukin-6 (IL-6), a proinflammatory cytokine, by endotoxin-activated murine macrophages. Both neuropeptides exhibit a dual effect on the IL-6 production by peritoneal macrophages. Whereas VIP and PACAP inhibit with similar dose-response curves the release of IL-6 from macrophages stimulated with a LPS dose range from 100 pg/mL to 10 microg/mL, both neuropeptides enhance IL-6 secretion in unstimulated macrophages and in macrophages stimulated with very low LPS concentrations (1-10 pg/mL). The inhibition on LPS-induced IL-6 production is specific, presumably mediated through a subtype of the PACAP-R. VIP and PACAP regulate the production of IL-6 at a transcriptional level. These results were correlated with an inhibition on both IL-6 expression and release in endotoxemic mice in vivo. These findings support the idea that in the absence of stimulation or in the presence of low doses of LPS, VIP and PACAP could play a role in immune system homeostasis. However, under toxicity conditions associated with high LPS doses, VIP and PACAP could act as protective mediators that regulate the excessive release of IL-6 in order to reduce inflammation or shock.

Adenylyl Cyclases↗

Tamoxifen does not improve survival of patients with advanced hepatocellular carcinoma.

To discover whether tamoxifen is able to extend the survival of patients with advanced hepatocellular carcinoma, we included 80 patients with cirrhosis and advanced hepatocellular carcinoma in a multicenter, double-blind, placebo-controlled trial in order to analyze the influence of treatment with tamoxifen on survival. The patients were randomized to receive tamoxifen, 40 mg/day (group 1), or placebo (group 2). Both groups were similar in age, sex, etiology of cirrhosis, biochemical, hematologic and hormonal parameters, morphology of the tumor (nodular vs multinodular or massive), Child-Pugh's score, and Okuda's stage. The 1-year survival rate was similar in both groups (30% in group 1 vs 37.8% in group 2; p = 0.31). Tamoxifen treatment was well tolerated by the patients. We conclude that tamoxifen does not extend the survival of patients with cirrhosis and advanced hepatocellular carcinoma.

Adult↗

Gender effect on apolipoprotein E epsilon4 allele-associated risk for sporadic Alzheimer's disease.

INTRODUCTION: The role of gender in Alzheimer's disease (AD), and its possible interaction with apolipoprotein E (apoE), has been controversial. MATERIAL AND METHODS: ApoE allelic frequencies and the effect of apoE epsilon4 allele dosage on risk and age at onset of AD were evaluated, separately for men and women, in 100 patients with sporadic AD and 100 age-matched controls. RESULTS: The distribution of apoE alleles and the odds ratio for AD, when associated with 1 or 2 epsilon4 alleles, were not statistically different between men and women. No effect of the dosage of the epsilon4 allele was found on the age at onset of dementia in the 2 sex groups. CONCLUSION: Our data suggest that the relation of the apoE genotype to AD is not dependent on sex.

Alleles↗

Molecular cloning, sequencing, and expression of a chemoreceptor gene from Leptospirillum ferrooxidans.

We have cloned and sequenced a 2,262-bp chromosomal DNA fragment from the chemolithoautotrophic acidophilic bacterium Leptospirillum ferrooxidans. This DNA contained an open reading frame for a 577-amino-acid protein showing several characteristics of the bacterial chemoreceptors and, therefore, we named this gene lcrI for Leptospirillum chemotaxis receptor I. This is the first sequence reported for a gene from L. ferrooxidans encoding a protein. The lcrI gene showed both sigma 28-like and sigma 70-like putative promoters. The LcrI deduced protein contained two hydrophobic regions most likely corresponding to the two transmembrane regions present in all of the methyl-accepting chemotaxis proteins (MCPs) which make them fold with both periplasmic and cytoplasmic domains. We have proposed a cytoplasmic domain for LcrI, which also contains the highly conserved domain (HCD region), present in all of the chemotactic receptors, and two probable methylation sites. The in vitro expression of a DNA plasmid containing the 2,262-bp fragment showed the synthesis of a 58-kDa protein which was immunoprecipitated by antibodies against the Tar protein (an MCP from Escherichia coli), confirming some degree of antigenic conservation. In addition, this 58-kDa protein was expressed in E. coli, being associated with its cytoplasmic membrane fraction. It was not possible to determine a chemotactic receptor function for LcrI expressed in E. coli. This was most likely due to the fact that the periplasmic pH of E. coli, which differs by 3 to 4 pH units from that of acidophilic chemolithotrophs, does not allow the right conformation for the LcrI periplasmic domain.

Amino Acid Sequence↗

[Thrombosis of the hepatic artery and portal vein secondary to invasive aspergillosis following liver transplantation].

Thrombosis of the main hepatic vessels is a severe, frequent complication in patients requiring liver transplantation. It is usually a cause of emergency retransplantation. Two cases of hepatic vascular thrombosis secondary to disseminated aspergillosis are presented. Both patients demonstrated a septic state and required a second transplantation despite which they died within a few days. Necropsy showed disseminated aspergillosis with invasion of the portal venous system and the hepatic artery. The risk factors associated with this infection and the possible pathogenic mechanisms are discussed.

Abscess↗

Compression bandaging effects on lower extremity peripheral and sub-bandage skin blood perfusion.

Laser-Doppler blood perfusion was simultaneously measured on both great toes and the lateral upper-calf before and during fore-foot-to-knee compression bandaging of one test-leg in ten vascularly healthy female volunteers. Two bandaging methods were sequentially used separated by a 30 minutes interval. Bandage A consisted of a layer of zinc impregnated gauze and an elastic wrap; bandage B had the elastic wrap only. Sub-bandage pressures of the test-leg were measured at distal and proximal lateral below-knee standardized sites. The study purpose was to determine the effects of moderate compression pressure achieved for bandages A under and distal to bandaged regions. Initial (mean +/- sem_ sub-bandage pressure achieved for bandages A and B were similar, being respectively 32.9 +/- 2.8 and 28.4 +/- 3.9 mm Hg. Both bandages types were associated with significant reductions in test-leg toe blood perfusion amounting to 44.2 +/- 13.1 percent and 27.5 +/- 10.5 percent for bandages A and B respectively. Contrastingly, test-leg sub-bandage blood perfusion did not differ from its pre-bandage baseline mean level for either bandage type. These findings show that a widely used bandaging method and a slight variant each significantly reduces distal (toe) blood perfusion without reducing sub-bandage skin perfusion. Absence of sub-bandage perfusion decreases may be related to a partially compensating reflex vasodilatory response, but such effects if present are inadequate to prevent reductions in distal perfusion. These results reinforce the need for due care and risk-benefit consideration with respect to therapeutic compression levels.

Adult↗

[Tonsillectomy by electrical dissection versus blunt dissection: a study of 838 cases (Randomized trial of 207 cases and non-randomized prospective study of 631 cases].

Tonsillectomy is one of the most common operations performed in the world and various techniques and instruments have evolved for this purpose. We report the results of two prospective studies: in the first study, blunt dissection was compared with electrodissection tonsillectomy (207 cases), and in the second study, 631 patients had their tonsils removed using only the electrodissection technique. Although electrodissection tonsillectomy is not common in Spain, in our experience it is simple, reliable and easy to learn. Its advantages include minimal bleeding, shorter operating time, and less postoperative hemorrhage. The postoperative morbidity is similar to that of blunt dissection.

Adult↗

Functional characterization and mRNA expression of pituitary adenylate cyclase activating polypeptide (PACAP) type I receptors in rat peritoneal macrophages.

The present work characterizes the mRNA expression of PACAP type I receptors in rat peritoneal macrophages but not in peritoneal lymphocytes by both retrotranscriptase and polymerase chain reaction (RT-PCR) and homologous Southern hybridization and the stimulation by PACAP27, PACAP38 and vasoactive intestinal peptide (VIP) of sn-1,2-diacylglycerol production in rat peritoneal macrophage membranes. The binding of [125I]PACAP27 was time and cell concentration dependent. Scatchard analysis of displacement of the bound tracer by unlabeled PACAP27 indicates the existence of two classes of binding sites. The dissociation constant (Kd) was 0.64 +/- 0.08 nM and the maximal binding capacity (Bmax) was 8.85 +/- 1.45 fmol/10(6) cells for the high affinity binding site. The low affinity binding site had a Kd of 0.10 +/- 0.06 microM with a Bmax of 300 +/- 21.9 fmol/10(6) cells. Scatchard analysis of VIP displacement data indicated the presence of two classes of binding sites with a Kd and Bmax different to those of PACAP27. These results suggest that PACAP binds to two binding sites, PACAP type I receptors and PACAP type II receptors. The PACAP27-stimulated diacylglycerol production was not affected by treatment with pertussis toxin. However, the presence of GTP partially inhibited this PACAP27 stimulation of 1,2-diacylglycerol in a dose dependent manner, although GTP alone stimulates diacylglycerol accumulation. In conclusion, for the first time we demonstrate by biochemical and molecular biology criteria the existence of PACAP type I receptors on rat peritoneal macrophages and the evidence for coupling with a pertussis toxin-insensitive G regulatory protein.

Adenylate Cyclase Toxin↗