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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
PubMed1999

Androgenic and anti-androgenic effects of progesterone derivatives with different halogens as substituents at the C-6 position.

The pharmacological activities of four pregnane derivatives: 17alpha-hydroxy-16beta-methylpregna-4,6-diene-3,20-dio ne (7), 17alpha-acetoxy-16beta-methylpregna-4,6-diene-3,20-dio ne (8), 17alpha-acetoxy-6-bromo-16beta-methylpregna-4,6-diene- 3,20-dione (10), and 17alpha-acetoxy-6-chloro-16beta-methylpregna-4,6-diene -3,20-dione (11), were determined. The derivatives were evaluated on gonadectomized male hamster flank organs and seminal vesicles. The results indicate that topical applications of testosterone (T) on the flank organs increased the diameter of the pigmented spot. Similarly, the same phenomenon occurred on the glands treated with compound 11, whereas compound 10 decreased the size of the spot significantly. In this study, we determined the effects of several new steroids on the conversion of T to DHT in flank organs and seminal vesicles. The results show that compound 10 inhibited T conversion to DHT, but compound 11, at a dose of 200 microg, stimulated T conversion in both flank organs and seminal vesicles. However, when 2 mg of compound 11 was applied, it inhibited the conversion of T to DHT, suggesting that this compound also represses gonadotropin release. The difference between compounds 10 and 11 involves the electronegativity of the halogen at the C-6 position of the progesterone skeleton. These data clearly indicate that by decreasing the electronegativity of the halogen at C-6 (compound 10), 5alpha-reductase is inhibited in both tissues and at different pHs. On the other hand, when the electronegativity of the halogen atom was increased (11), there was a much lower inhibitory effect on the conversion of T to DHT.

Androgen Antagonists↗
PubMed1999

Cognitive-behavioral treatment for rapists: can we do better?

A review of treatment studies with rapists suggests that the currently used cognitive-behavioral treatment strategies remain limited in their success. The current article proposes that some reasons for the limited success may be that current treatment approaches do not adequately address the heterogeneity of the population, emphasize changing patterns of physiological arousal and cognitive distortions rather than psychological acceptance, and neglect to address differences in the function of sexually aggressive behavior among individuals. With the hope of decreasing rates of victimization and preventing recidivism by rapists, this article offers several treatment suggestions that should be tested empirically to determine if treatment efficacy can be increased with this population.

Aggression↗
PubMed1999

Oxidative transformations of guaia-1(10)-en-12,8-olides into xanthanolides

Dihydropsuedoivalin (1) was isolated from Stevia tomentosa, which, when treated with base, afforded epidihydropseudoivalin (2). The stereochemistry of 1 and 2 was established by crystallographic X-ray studies of the two derivatives of epidihydropseudoivalin. Treatment of 1 and 2 with Jones's reagent afforded the xanthanolides 3 and 4, respectively.

Journal Article↗
PubMed1998

Enhanced antibody and cytokine responses to influenza viral antigens in perforin-deficient mice.

Cytotoxic T lymphocytes (CTL) lyse virus-infected target cells by secreting the pore-forming effector molecule, perforin. Perforin-mediated cell death appears to be a major mechanism in viral clearance but its role in regulating immune responses in vivo is unclear. In this report, we show that following immunization with influenza viral antigens, perforin-deficient mice generated about 100-fold greater serum antibody responses than wild-type mice. Further, immune spleen cells from perforin knock-out mice secreted over 10-fold more IFN-gamma following in vitro restimulation than immune spleen cells from control mice. Finally, there were over 10-fold more IFN-gamma-secreting cells in cultures from perforin-deficient mice than those from control mice, suggesting that the enhanced cytokine release by T cells from perforin-deficient mice is due to an increase in the effector cell pool. Collectively, these results suggest that perforin-mediated effector function is required in the down-regulation of the immune response by way of limiting antigen-presenting cell function.

Animals↗
PubMed1998

Expression of brain-derived neurotrophic factor and its cognate receptor, TrkB, in the rat suprachiasmatic nucleus.

Photic entrainment of mammalian circadian rhythms occurs because the pacemaker in the suprachiasmatic nuclei (SCN) of the hypothalamus is endowed with a rhythmic sensitivity to photic signals conveyed by the retinohypothalamic tract. Since brain-derived neurotrophic factor (BDNF) has been implicated in the functional modulation of other retinal targets, the rat SCN was examined for expression and cellular distribution of this neurotrophin and TrkB, the tyrosine kinase receptor that preferentially binds BDNF. The rat SCN was found to express the mature BDNF peptide and mRNA by Western blotting, enzyme-linked immunosorbent assay (ELISA), and reverse transcription-polymerase chain reaction (RT-PCR) analyses. BDNF-immunoreactivity and hybridization signal for its mRNA were coextensively localized within a number of SCN cells throughout the rostrocaudal axis of each nucleus. In addition, some cells intercalated within the optic chiasm were distinguished by expression of BDNF immunoreactivity or mRNA. Immunostaining for the TrkB receptor was also evident in the SCN within terminals or fibers predominantly located along the SCN/optic chiasm interface and within scattered perikarya near the medial border of each nucleus. Combined in situ hybridization and immunocytochemical analysis revealed that BDNF mRNA-expressing cells within the ventrolateral SCN were often closely apposed to TrkB-positive fibers extending from the optic chiasm. These findings raise the possibility that target-derived interactions between BDNF and TrkB receptors could play a role in the circadian modulation of SCN pacemaker sensitivity to photic input transmitted by the retinohypothalamic tract.

Animals↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1996

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↗
PubMed1996

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↗