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Biomedical subjects

R Miranda

Publications and source records attributed to R Miranda.

At least 37 records · Page 2Linked to original sources

Enhanced immune responses and resistance against infection in aged mice conferred by Flu-ISCOMs vaccine correlate with up-regulation of costimulatory molecule CD86.

Ageing is associated with a decline in immune function and our primary objective is to 'reverse' age-related decline in protective immune responses to vaccination by formulating vaccines in appropriate delivery systems. In this paper, we demonstrate that influenza vaccine formulated as ISCOMs is highly immunogenic and confers protection in aged mice, when compared to current influenza vaccine. The enhanced protection conferred by Flu-ISCOMs in aged mice correlates with the up-regulation of co-stimulatory molecule, CD86 (B7.2) and to a lesser extent, CD80 (B7.1) expression on antigen presenting cells.

Aging↗

Colonic volvulus and ulcerative jejunoileitis due to occult celiac sprue.

Colonic volvulus is a rare complication of celiac disease. A case is reported of a 46-year-old man with a long-standing history of diarrhea and abdominal distention with a diagnosis of irritable bowel syndrome. After an elective inguinal hernia repair, a cecal volvulus and an ulcerative jejunoileitis developed in the patient that required an extensive intestinal resection. Short bowel syndrome developed and was treated with total parenteral and enteral nutrition. The patient had a poor course after reinitiation of oral diet. Subsequently, celiac sprue was diagnosed and the patient improved with a gluten-free diet.

Celiac Disease↗

Inhibitory effect of propranolol on lipid synthesis in gonadectomized male hamster flank organs.

BACKGROUND: This paper describes the inhibitory effect produced by propranolol pre-treatment on lipid synthesis in flank organs from intact, gonadectomized, and isoproterenol-treated male hamsters. Furthermore, the effect induced by the same treatments on gland sebum composition is reported. METHODS: Different groups of male hamsters were injected daily with propranolol, isoproterenol or propranolol plus isoproterenol. Treatment-effect was evaluated determining the in vitro incorporation of radioactive acetate into lipids in hamster flank organs from intact and castrated animals. Additionally, radiolabeled lipids were isolated and identified using TLC and autoradiography as methods. RESULTS: Results demonstrate that castration significantly decreases lipid synthesis in male hamster flank organs. In addition, propranolol treatment inhibits such synthesis in glands from intact, gonadectomized, and isoproterenol-treated animals. However, isoproterenol treatment was ineffective when compared to intact or gonadectomized control vehicle-treated animals. Lipid classes isolated and identified lipids either in castrated or in drug-treated animals were phospholipids, cholesterol, monoglycerides, fatty acids, waxes and cholesterol esters. CONCLUSIONS: Results indicate an inhibitory effect induced on lipid synthesis by beta-adrenergic receptor antagonists; however, beta-adrenergic agonists drugs do not stimulate it. Data suggest a permissive role of adrenergic hormones on lipid synthesis in intact and in gonadectomized animals. Furthermore, castration decreased the synthesis, suggesting that a tight coupling between beta-adrenergic receptors and androgen receptors may be a prerequisite for lipogenesis in this tissue. Pre-treatment does not modify sebum composition in gonadectomized animal glands. These data support the evidence that activation of beta-adrenergic receptors could be an independent factor in the lipid composition regulation process.

Animals↗

Self antigens expressed by solid tumors Do not efficiently stimulate naive or activated T cells: implications for immunotherapy.

Induction and maintenance of cytotoxic T lymphocyte (CTL) activity specific for a primary endogenous tumor was investigated in vivo. The simian virus 40 T antigen (Tag) expressed under the control of the rat insulin promoter (RIP) induced pancreatic beta-cell tumors producing insulin, causing progressive hypoglycemia. As an endogenous tumor antigen, the lymphocytic choriomeningitis virus (LCMV) glycoprotein (GP) was introduced also under the control of the RIP. No significant spontaneous CTL activation against GP was observed. However, LCMV infection induced an antitumor CTL response which efficiently reduced the tumor mass, resulting in temporarily normalized blood glucose levels and prolonged survival of double transgenic RIP(GP x Tag2) mice (137 +/- 18 d) as opposed to control RIP-Tag2 mice (88 +/- 8 d). Surprisingly, the tumor-specific CTL response was not sustained despite the facts that the tumor cells continued to express MHC class I and LCMV-GP-specific CTLs were present and not tolerized. Subsequent adoptive transfer of virus activated spleen cells into RIP(GP x Tag2) mice further prolonged survival (168 +/- 11 d), demonstrating continued expression of the LCMV-GP tumor antigen and MHC class I. The data show that the tumor did not spontaneously induce or maintain an activated CTL response, revealing a profound lack of immunogenicity in vivo. Therefore, repetitive immunizations are necessary for prolonged antitumor immunotherapy. In addition, the data suggest that the risk for induction of chronic autoimmune diseases is limited, which may encourage immunotherapy against antigens selectively but not exclusively expressed by the tumor.

Adoptive Transfer↗

Stimulatory effect of progesterone and 5 beta-progesterone on lipid synthesis in hamster flank organs.

In order to study lipid synthesis in female hamster flank organs during the estrous cycle, glands were obtained from different animals during different phases of the cycle. Lipid metabolism of [U-14C]glucose was studied under in vitro conditions. The radioactive lipids formed, were extracted from the glands and quantified. An aliquot of the extract was submitted to TLC to isolate and identify the lipids formed. Lipid synthesis in the glands increased significantly during estrous compared with the diestrous phase, suggesting the influence of sex hormones on lipid metabolism in flank organs. The radioactive lipids isolated and identified were: phospholipids, cholesterol, glycerides, waxes, and cholesterol esters. The percentages of conversation from [U-14C]glucose to cholesterol esters were minor in extracts from glands of diestrous animals as compared to estrous and proestrous animals, whereas glycerides and waxes increased significantly in metestrous and diestrous animals. To verify and evaluate the role of estrogen and progesterone in lipid synthesis, three different groups of gonadectomized female hamsters were injected daily with estradiol, progesterone, and 5 alpha-progesterone. After treatments, glands were incubated with [U-14C]glucose to determine the incorporation of radioactive glucose into lipids under culture conditions. The radioactive lipids synthesized were subsequently extracted and identified. The results showed that estrogen had no effect on in vitro [U-14C]glucose incorporation into lipids by flank organs, compared to the vehicle, whereas progesterone and 5 alpha-progesterone increased radioactive lipid synthesis by the glands significantly (p < 0.05). The radioactive lipids isolated and identified from extracts of gonadectomized female hamster flank organs were: phospholipids, cholesterol, triglycerides, waxes, and cholesterol esters. Gonadectomy increased phospholipid synthesis and decreased that of monoglycerides, diglycerides, and waxes. The percentages of conversion from [U-14C]glucose to cholesterol esters were higher after progesterone and 5 alpha-progesterone treatments than in vehicle and estrogen-treatments. Our data indicate that progesterone and 5 alpha-progesterone-treatments increased the in vitro [U-14C]glucose incorporation into lipids in flank organs from gonadectomized female hamsters. Furthermore, the major lipid synthesized by glands under these stimuli were cholesterol fatty acids. Thus, progesterone and 5 alpha-progesterone alter the consistency of sebum from gonadectomized female glands.

Animals↗

Laparoscopic cholecystectomy as an outpatient procedure.

BACKGROUND: Laparoscopic cholecystectomy is still done mainly on an inpatient basis at hospitals or on an outpatient basis at ambulatory care departments inside hospitals. STUDY DESIGN: We reviewed 213 cases in which outpatient laparoscopic cholecystectomy was done at an ambulatory surgical center not associated with a hospital physically or administratively. Patients were selected solely on the basis of medical history and physical examination results. Patients received general anesthesia as is typical for outpatient procedures. Narcotic use was minimized to prevent postoperative nausea. The procedure did not include intraoperative cholangiography. RESULTS: Laparoscopic cholecystectomy took 1 to 2 hours in three quarters of patients. Rate of conversion to open cholecystectomy was 2.8% (6 of 213 patients). The mean recovery period was 6.6 hours, and 97% of patients were discharged on the same day (ie, were treated as outpatients). We identified no cases of retained common duct stone. Wound complications included mainly seroma, wound seepage, and wound infection; 18% of these complications were seen at trocar sites. No major complications were seen. CONCLUSIONS: Elective outpatient laparoscopic cholecystectomy can be done safely with low morbidity, high patient acceptance, and same-day discharge in > 95% of cases.

Ambulatory Surgical Procedures↗

Paroxetine increases heart rate variability in panic disorder.

Panic patients have decreased heart rate variability, a risk factor for sudden cardiac death, and increased rates of cardiac death and stroke. Imipramine has been found to further reduce heart rate variability in panic. This study uses power spectral analysis to compare autonomic components of heart rate variability in 16 unmedicated control subjects and 17 panic patients before and after treatment with paroxetine at 20 mg/day for 4 weeks. Patients had higher predrug reclining and standing sympathetic activity than control subjects. After drug, patients' total sympathetic activity decreased. Predrug patients failed to increase sympathetic activity on orthostasis, lacking the normal baroreflex response found in control subjects. After drug, patients normalized this sympathetic component of the baroreflex response. Before drug, patients' parasympathetic reclining and standing activity did not differ from control subjects, and patients showed the normal orthostatic parasympathetic decrease. After drug, patients' total parasympathetic activity increased, whereas the baroreflex response was preserved. Nine medicated patients had more than a 50% reduction of panic attacks. In view of paroxetine's increase of heart rate variability, potential benefits of selective serotonin reuptake inhibitors in decreasing cardiac mortality in panic disorder are discussed.

Adult↗

Increased synthesis of cholesterol stearate in flanking organ from gonadectomized female hamsters treated with progesterone and 5 alpha-dihydroprogesterone.

We demonstrated for the first time that progesterone and 5 alpha-dihydroprogesterone stimulate [U-14C]glucose incorporation into lipids in gonadectomized female hamster flanking organs. We also found that cholesterol stearate is the major lipid synthesized female hamster flanking organs under progesterone and 5 alpha-dihydroprogesterone stimulation. In this manner, progesterone and 5 alpha-dihydroprogesterone alter the consistency of sebum from gonadectomized female glands.

5-alpha-Dihydroprogesterone↗

Identification and analysis of the u6 small nuclear RNA gene from Entamoeba histolytica.

Among the small nuclear RNAs (snRNAs) involved in the spliceosomal processing of pre-mRNA, U6 is the most conserved. As a first evidence for the presence of the splicing machinery in the amitochondrial protozoan Entamoeba histolytica (Eh), we have cloned the u6 snRNA gene. We find that in this organism u6 is a single copy gene that is transcribed as a poly(A)- RNA molecule of approximately 105 nucleotides. We have mapped the 5' end of the U6 snRNA transcript, and identified typical elements of a putative polymerase III promoter. This is the first snRNA gene reported in Eh. Sequence analysis indicates that this gene contains all the conserved nucleotides known to be important for U6 snRNA function. These results, in conjunction with the earlier finding of genes that contain pre-mRNA introns, suggest that Eh has a functional spliceosomal complex.

Animals↗

Circular nodes in neural networks.

In the usual construction of a neural network, the individual nodes store and transmit real numbers that lie in an interval on the real line; the values are often envisioned as amplitudes. In this article we present a design for a circular node, which is capable of storing and transmitting angular information. We develop the forward and backward propagation formulas for a network containing circular nodes. We show how the use of circular nodes may facilitate the characterization and parameterization of periodic phenomena in general. We describe applications to constructing circular self-maps, periodic compression, and one-dimensional manifold decomposition. We show that a circular node may be used to construct a homeomorphism between a trefoil knot in R3 and a unit circle. We give an application with a network that encodes the dynamic system on the limit cycle of the Kuramoto-Sivashinsky equation. This is achieved by incorporating a circular node in the bottleneck layer of a three-hidden-layer bottleneck network architecture. Exploiting circular nodes systematically offers a neural network alternative to Fourier series decomposition in approximating periodic or almost periodic functions.

Neural Networks, Computer↗

Nerve growth factor (NGF) regulation of estrogen receptors in explant cultures of the developing forebrain.

Estrogen profoundly affects the organization of the nervous system. Its receptor, a nuclear transcription factor, is widely expressed in the developing forebrain. Earlier work established that forebrain estrogen target neurons coexpress nerve growth factor (NGF) receptors and receptor mRNA. The present study examined the regulation of forebrain estrogen receptors by NGF, using organotypic cultures of the developing cerebral cortex and basal forebrain. NGF significantly increased nuclear estrogen binding in cortical but not basal forebrain explants. Both cortical and basal forebrain explant cultures express the NGF receptor, TrkA. However, our earlier observation that developing cortical neurons, unlike basal forebrain neurons, widely coexpress mRNAs for NGF and its cognate receptors, suggests that in the present study cortical neuronal responses to exogenous NGF may have been primed by autocrine mechanisms. Alterations in nuclear estrogen binding but not estrogen receptor mRNA levels suggests that NGF may regulate cortical estrogen receptors posttranscriptionally.

Animals↗

Delayed primary repair of intrathoracic esophageal perforation: is it safe?

The management of intrathoracic esophageal perforation with delayed diagnosis is a subject of controversy. Because of the obvious advantages of primary repair as a simple single-stage operation, this technique was preferentially used to treat 18 of 22 consecutive patients with esophageal perforation. These patients were stratified into three groups according to the time interval between perforation and repair: group A, less than 6 hours, five patients (28%); group B, 6 to 24 hours, six patients (33%); and group C, more than 24 hours, seven patients (39%). Group A patients were older (p < 0.05) and group B had fewer iatrogenic perforations (B, 17%; A, 80%; C, 57%, p < 0.1). Additional tissue was used to buttress the repair site in all three groups (A, 3/5 patients, 60%; B, 4/6 patients, 67%; C, 6/7 patients, 86%; p = not significant). In seven patients (39%), a fundic wrap was used to reinforce the site of primary repair. The outcomes of the three groups were analyzed. Group A had the lowest proportion of postoperative leaks (A, 0/4 patients, 0%; B, 4/6 patients, 67%; C, 5/6 patients, 83%; p < 0.05) and postoperative morbidity (A, 2/5 patients, 40%; B, 6/6 patients, 100%; C, 6/7 patients, 86%; p < 0.1). However the increased incidence of leak and morbidity did not lead to an increase in mortality. One death occurred in each group, with an overall mortality of 17% (A, 1/5 patients, 20%; B, 1/6 patients, 17%; C, 1/7 patients, 14%; p = not significant). We conclude that in the era of advanced intensive care capabilities, primary repair of intrathoracic esophageal perforation can be safely accomplished in most patients regardless of the time interval between perforation and operation. Leakage at the suture site is common unless primary repair is carried out without delay. Postoperative leakage, however, is usually inconsequential and does not necessarily result in an adverse outcome.

Aged↗

Immunohistochemical detection of parathyroid hormone-related protein in a rare variant of hepatic neoplasm (sclerosing hepatic carcinoma).

Sclerosing hepatic carcinoma represents an uncommon subtype of hepatic malignancy, frequently associated with hypercalcemia. We applied immunohistochemistry using the avidin-biotin-complex technique to examine the presence of parathyroid hormone-related protein (PTHrP) in formalin-fixed and paraffin-embedded sections of tissue from a case of sclerosing hepatic carcinoma obtained at autopsy. Two polyclonal antibodies against the regions 24 to 35 and 107 to 111 of human PTHrP, and a monoclonal antibody that recognizes the human sequence 38 to 64 of this protein, were used. Preabsortion tests using the corresponding synthetic peptide as antigen were done with these antibodies. The neoplastic tissue displayed cytoplasmic immunostaining, diffuse with the antibodies against the amino- or carboxy-terminal regions of PTHrP, and with a predominant peripheral pattern when using the antibody to the midregion of the molecule. Tumor cells positive for PTHrP were also positive for hepatocellular markers cytokeratins 10, 17, and 18, but negative for chromogranin A. Our findings provide the first evidence for PTHrP production in the sclerosing subtype of hepatic carcinoma.

Antibodies, Monoclonal↗

Burkitt's lymphoma in Brazil: strong association with Epstein-Barr virus.

The incidence of Burkitt's lymphoma (BL) in Brazil is intermediate between the endemic form of equatorial Africa and the sporadic form in the United States. To characterize these lymphomas, we evaluated the clinical, morphologic, and immunohistochemical features of 24 Brazilian cases of BL. We also analyzed the cases for the presence of Epstein-Barr virus (EBV)-RNA using a highly sensitive and specific method of in situ hybridization. Most cases presented with involvement of intraabdominal organs, similar to the sporadic form of BL. EBV-RNA was detected in 17 of 24 cases (71%) in all or virtually all the tumor cells. This prevalence of EBV-positivity in our cases is intermediate between the endemic form of BL in equatorial Africa (100%) and the sporadic form in the United States (30%). These findings suggest that EBV plays an important role in the pathogenesis of BL in Brazil. This intermediate incidence of EBV infection may explain in part the differences of incidence of BL in different geographic regions.

Adolescent↗

Chelation therapy.

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Chelation Therapy↗