Thyroid carcinoma on an ovarian teratoma: a case report and review of the literature.
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Abortion, Spontaneous↗
Biomedical subjects
J R Rodriguez
Publications and source records attributed to J R Rodriguez.
A striking property of recombinant poxviruses: efficient inducers of in vivo expansion of primed CD8(+) T cells.
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Animals↗
Screening of obstructive sleep apnoea: heart rate spectral analysis of nocturnal pulse oximetric recording.
Using heart rate spectral analysis of nocturnal pulse oximetry, we prospectively evaluated the utility of this methodology in patients clinically suspected of having obstructive sleep apnoea (OSA). A hundred and ninety-seven outpatients referred with symptoms compatible with the diagnosis of OSA were studied. All participants had nocturnal pulse oximetry performed simultaneously with conventional polysomnography. Power density of heart rate obtained by nocturnal pulse oximetry was analysed using fast Fourier transformation of a Hamming-windowed signal. Recording test results were classified as abnormal (suspicion of OSA) in the presence of a peak in the periodogram between period boundaries 30-70 sec. A normal test result was defined as the absence of the 30-70 sec peak in the periodogram. The total area of the periodogram (S(TOT)), the area enclosed in the periodogram between the period boundaries 30-70 sec (S(30-70)), the area enclosed in the period boundaries 30-70 sec with respect to the total area of the periodogram (S) and the peak amplitude 30-70 sec (PA) were measured. The presence of a peak in the periodogram has a sensitivity of 81.3%, a specificity of 91.5% a positive predictive value of 89.1% and a negative predictive value of 85.1% for OSA diagnosis. The OSA patients were found to have higher values of S(TOT), S(30-70), S and PA than the non OSA patients. Receiver operating characteristics (ROC) curve was constructed at different thresholds of S(TOT), S(30-70) S and PA. For a PA threshold of 10(%)2, heart rate spectra analysis sensitivity for OSA was 58% and specificity was 92%. Furthermore, the positive and negative predictive values for diagnosis of OSA were 87 and 72% respectively. Apnoea hypopnea index (AHI) correlated significantly with S(TOT) (r=0.44; P<0.001), S(30-70) (r=0.59: P<0.001), S (r=0.58; P<0.001) and PA (r=0.58; P<0.001). According to our results, heart rate spectral analys s obtained by nocturnal pulse oximetry and identification of peak in the periodogram between period boundaries 30-70 sec could be useful as a diagnostic technique for OSA patients.
Adult↗
Iodine-131 treatment of thyroid papillary carcinoma in patients undergoing dialysis for chronic renal failure: a dosimetric method.
Until recently, the therapeutic protocol widely accepted for ablation of the thyroid remnant and for metastases of thyroid papillary carcinoma was the administration of 131I after surgery. However, at present, some data question the usefulness of such treatment in patients considered low risk. The treatment with radioiodine in patients suffering from end-stage renal disease (ESRD) undergoing hemodialysis requires controlled dosages and individualized administration guidelines. The need to include these patients on the waiting list for a renal transplantation, once they have overcome the disease, and the higher prevalence of thyroid carcinoma in ESRD patients makes this an increasingly significant problem. The cases reported in the literature are few and the therapeutic models followed are very difficult. In this paper we propose a therapeutic model that provides the highest thyroid ablative dosage, minimizing radiation exposure to the rest of the organs. The main difference between our protocol and that already described is the performance of daily hemodialysis during the first 5 days of treatment, as well as the administration of a dose of 131I equivalent to that administered to patients who show normal renal function.
Adult↗
Differential antifungal activity of isomeric forms of nystatin.
When nystatin is placed in RPMI and other biological fluids, there is loss of pure nystatin, with the development of two distinguishable chromatographic peaks, 1 and 2. Peak 1 appears identical to commercially prepared nystatin. By nuclear magnetic resonance (NMR) and mass spectral analysis, peak 2 appears to be an isomer of peak 1. The isomers are quantitatively and fully interconvertible. Formation of peak 2 is accelerated at a pH of >7.0 and ultimately reaches a near 55:45 (peak 1/peak 2 ratio) mixture. We sought to determine the relative activities of peaks 1 and 2 against Candida spp. Peak 2 consistently showed higher MICs when it was the predominant form during the experiment. Time-kill analyses showed that peak 2 required > or =8 x the concentration of peak 1 to produce a modest and delayed killing effect, which was never of the same magnitude as that produced by peak 1. In both types of assays, the activity of peak 2 corresponded with intra-assay formation of peak 1. Both MIC measurements and time-kill analysis suggest that peak 2 has considerably less activity, if any at all, against Candida spp. Peak 2 may serve as a reservoir for peak 1.
Antifungal Agents↗
Immunogenicity of Ty-VLP bearing a CD8(+) T cell epitope of the CS protein of P. yoelii: enhanced memory response by boosting with recombinant vaccinia virus.
We characterized the immunogenicity of the hybrid Ty-virus-like carrying the CD8(+) T cell epitope (SYVPSAEQI) of the circumsporozoite (CS) protein of Plasmodium yoelii (TyCS-VLP), a rodent malaria parasite. Balb/c mice were immunized with hybrid TyCS-VLP, and their CS-specific CD8(+) T cell response was quantitatively evaluated with the ELISPOT assay, based on the enumeration of epitope specific gamma-interferon secreting CD8(+) T cell. A single immunization with the TyCS-VLP by a variety of routes and doses indicated that the maximal response occurred in mice, which were immunized with 50 micrograms of these particles, administered via intramuscular. Combined immunization of mice with this TyCS-VLP followed by recombinant vaccinia virus expressing the entire P. yoelii CS protein (VacPyCS) or irradiated sporozoites, induced high levels of IFN-gamma-producing cells. The immunization regime, priming with TyCS-VLP and boosting with VacPyCS generated a potent protective immune response, which strongly inhibited P. yoelii liver stages development and protected 62% of the mice against a subsequent live P. yoelii sporozoite challenge.
Animals↗
Slender and stumpy bloodstream forms of Trypanosoma brucei display a differential response to extracellular acidic and proteolytic stress.
Natural infections of mammals with African trypanosomes, such as Trypanosoma brucei, are generally pleomorphic, the population consisting of different forms, termed slender and stumpy forms, that vary in number as the parasitaemia develops. We show that the differentiation of slender into stumpy forms is characterized by the acquisition by the parasite of the ability to regulate its internal pH, even in the face of a large, inwardly directed gradient of H+, as well as a tolerance towards external proteolytic stress. These adaptations effectively abbrogate cellular stress-activated signalling pathways involving adenylate cyclase and glycosylphosphoinositol-specific phospholipase-C mediated release of the surface coat. Although in metabolic terms stumpy forms of the parasite are considered to be preadapted to life in the arthropod vector, these data clearly demonstrate that these forms also possess additional cellular adaptations designed to deal with the immediate and potentially harmful changes in the extracellular environment that occur upon ingestion of a bloodmeal by the tsetse fly vector.
Acid-Base Equilibrium↗
Airway disorders and pulmonary function in snorers. A population-based study.
The aim of our study was to determine the relationship between snoring, airway disorders and pulmonary function in the general population. We performed a stratified random sampling from the population (n = 92,364). Four hundred subjects agreed to participate and were invited to the clinic, where a detailed medical history, physical examination, spirometric test and maximal respiratory pressures measurements were carried out. Snoring was reported by 152 subjects (38%). Nasal obstruction and the presence of abnormal pharynx exploration were more frequent in subjects with snoring. Age, body mass index and neck circumference were significantly higher in the snorer group. In addition, we found that the non-snoring group had a significantly higher frequency of tonsillectomy during infancy and adolescence than the snorer group. We did not detect any significant difference in spirometric test values or in maximal respiratory pressure values between snorer group and non-snorer group. In conclusion, in the general population snoring is associated with nasal obstruction and abnormal pharynx exploration. Furthermore, snoring appears not to be associated with modifications in spirometric or in maximal respiratory pressure tests.
Adult↗
Aromatase expression by astrocytes after brain injury: implications for local estrogen formation in brain repair.
Recent evidence indicates that 17beta-estradiol may have neuroprotective and neuroregenerative properties. Estradiol is formed locally in neural tissue from precursor androgens. The expression of aromatase, the enzyme that catalyses the conversion of androgens to estrogens, is restricted, under normal circumstances, to specific neuronal populations. These neurons are located in brain areas in which local estrogen formation may be involved in neuroendocrine control and in the modulation of reproductive or sex dimorphic behaviours. In this study the distribution of aromatase immunoreactivity has been assessed in the brain of mice and rats after a neurotoxic lesion induced by the systemic administration of kainic acid. This treatment resulted in the induction of aromatase expression by reactive glia in the hippocampus and in other brain areas that are affected by kainic acid. The reactive glia were identified as astrocytes by co-localization of aromatase with glial fibrillary acidic protein and by ultrastructural analysis. No immunoreactive astrocytes were detected in control animals. The same result, the de novo induction of aromatase expression in reactive astrocytes on the hippocampus, was observed after a penetrating brain injury. Furthermore, using a 3H2O assay, aromatase activity was found to increase significantly in the injured hippocampus. These findings indicate that although astrocytes do not normally express aromatase, the enzyme expression is induced in these glial cells by different forms of brain injury. The results suggest a role for local astroglial estrogen formation in brain repair.
Animals↗
Prevalence of sleep disordered breathing and sleep apnea in 50- to 70-year-old individuals. A survey.
PURPOSE: To determine the prevalence of sleep disordered breathing (SDB) and sleep apnea syndrome (SAS) in a general population aged from 50 to 70 years. SUBJECTS AND METHODS: We recruited 76 individuals aged between 50 and 70 years, chosen at random from the electoral census. They were invited to the clinic where a detailed medical history was taken and physical examination, ENT examination, pulmonary function tests and night time recording of respiratory variables performed. RESULTS: The prevalence of SDB (apnea-hypopnea index >/= 5) was 28.9%, and there were no differences between men (28%) and women (30%). However, the prevalence of SAS was 6.8%, and there were differences between men (5 cases) and women (0 cases) (p = 0.0521). Subjects in the SDB group had higher systolic blood pressure than in the non-SDB group (p < 0.05). CONCLUSIONS: SDB and SAS are common among 50- to 70-year olds. The prevalence of SDB was 28.9% and the prevalence of SAS was 6.8%.
Aged↗
Oximetry spectral analysis in the diagnosis of obstructive sleep apnoea.
Using spectral analysis of oximetry data, we prospectively evaluated the validity of this methodology in patients clinically suspected of suffering from obstructive sleep apnoea (OSA). A total of 233 outpatients were studied. Nocturnal oximetry was performed simultaneously with conventional polysomnography for all participants. The power density of oxygen saturation was analysed using Fast-Fourier transformation of the oximetric signal. Nocturnal oximetry test results were considered as abnormal (suspicion of OSA) if a peak in the spectrum between the period boundaries 30 and 70 s was observed. A normal test result was defined as the absence of the 30-70 s peak from the spectrum. Single-blind evaluation was performed by three independent observers, and agreement of two or more of these was considered definitive. The peak amplitude and the ratio of the area enclosed in the 30-70 s peak to the total area of the spectrum (r(S)) were measured. The presence of a peak has a sensitivity of 78%, a specificity of 89%, a positive predictive value of 89% and a negative predictive value of 78%. Apnoea-hypopnoea indexes were correlated significantly with peak amplitude (r=0.74; P<0.001) and with r(S) (r=0.69; P<0.001). For a peak amplitude threshold of 0.7%(2), the sensitivity was 94% and the specificity was 65% for OSA diagnosis. Using a threshold for r(S) of 0.15, the sensitivity was 91% and the specificity was 67%. Thus the spectral analysis of nocturnal oximetry and identification of a peak at 30-70 s could be useful as a diagnostic technique for OSA subjects.
Adult↗
Recombinant viruses expressing a human malaria antigen can elicit potentially protective immune CD8+ responses in mice.
Extensive studies on protective immunity to rodent malaria provided the basis for the current experiments in which mice were immunized with recombinant (re) influenza and vaccinia viruses expressing selected sequences of the circumsporozoite (CS) protein of the human malaria parasite Plasmodium falciparum. Mice of different H-2 haplotypes immunized with re influenza viruses expressing the immunodominant B cell epitope of this CS protein produced high titers of antibodies to the parasite. A cytotoxic T lymphocyte epitope of the CS protein of P. falciparum, PF3, recognized by CD8+ T cells of H-2(k) mice, was expressed in a re vaccinia virus (VacPf) and a re influenza virus (FluPf). Immunization of mice with either FluPf or VacPf elicited a modest CS-specific CD8+ T cell response detected by interferon gamma secretion of individual immune cells. Priming of mice with FluPf, followed by a booster with VacPf, resulted in a striking enhancement of this T cell response. The reverse protocol, i.e., priming with VacPf followed by a booster with FluPf, failed to enhance the primary response. VacPf also greatly enhanced the primary response of mice injected with P. falciparum sporozoites or with a lipopeptide containing PF3. A booster with FluPf also amplified the response of lipopeptide- or sporozoite-primed mice but less than a VacPf booster did. Although mice are not susceptible to infection by P. falciparum sporozoites, we demonstrated that administration of two distinct immunogens expressing PF3 elicited activated, extravasating CS-specific T cells that protected against an intracerebral VacPf challenge.
Amino Acid Sequence↗
Localization of the insulin-like growth factor I receptor in the cerebellum and hypothalamus of adult rats: an electron microscopic study.
Insulin-like growth factor I (IGF-I) is an important modulator of cell growth and plasticity in the CNS. Expression of the IGF-I receptor mRNA in brain peaks at times of active cell development perinatally and remains detectable, albeit at lower levels, in the adult. While both autoradiographic and in situ hybridization studies show a wide and specific distribution of IGF-I receptor throughout the adult rat brain, nothing is yet known about its subcellular localization, a critical issue that will help clarify the biological role of this trophic factor in the adult brain. The present study describes the subcellular localization of IGF-I receptor immunoreactivity in the cerebellar cortex and the hypothalamic arcuate nucleus by using electron microscopic immunocytochemistry. In the cerebellum, IGF-I receptor immunoreactivity is present postsynaptically in the dendrites and soma of the Purkinje cell and presynaptically in axon terminals impinging upon the Purkinje cell soma, as well as in mossy fibre rosettes in the cerebellar glomeruli. Neurons in the mediobasal hypothalamus also contain IGF-I receptors located pre- and postsynaptically. Endothelial cells, astroglial end-feet surrounding micro vessels thoughout all the brain parenchyma, tanycytes of the third ventricle and oligodendrocytes in the cerebellar white matter are also rich in IGF-I receptors. These results strongly support previous observations that IGF-I is a neuromodulator in the adult brain, probably acting as both a pre- and a postsynaptic messenger. They also suggest that glial cells may be involved in the actions of IGF-I in the adult brain.
Age Factors↗
Vaccinia virus membrane proteins p8 and p16 are cotranslationally inserted into the rough endoplasmic reticulum and retained in the intermediate compartment.
The use of two-dimensional gel electrophoresis has identified the gene products A14L (p16) and A13L (p8) as abundant membrane proteins of the first infectious form of vaccinia virus, the intracellular mature virus (IMV; O. N. Jensen, T. Houthaeve, A. Shevchenko, S. Cudmore, T. Ashford, M. Mann, G. Griffiths, J. Krijnse Locker, J. Virol. 70:7485-7497, 1996). In this study, these two proteins were characterized in detail. In infected cells, both proteins localize not only to the viral membranes but also to tubular-cisternal membranes of the intermediate compartment, defined by the use of antibodies to either rab1A or p21, which colocalize with rab1A (J. Krijnse Locker, S. Schleich, D. Rodriguez, B. Goud, E. J. Snijder, and G. Griffiths, J. Biol. Chem. 271:14950-14958, 1996). Both proteins appear to reach this destination via cotranslational insertion into the rough endoplasmic reticulum, as shown by in vitro translation and translocation experiments. Whereas p16 probably spans the membrane twice, p8 is inserted into the membrane by means of its single NH2-terminal hydrophobic domain, adopting a topology which leaves the C terminus exposed to the cytoplasm. Combined immunocytochemical and biochemical data show that p16 is a member of the inner of the two IMV membrane layers, whereas p8 localizes to both the inner and the outer membrane. These findings are discussed with respect to our model of IMV membrane assembly.
Blotting, Western↗
Characterization of in vivo primary and secondary CD8+ T cell responses induced by recombinant influenza and vaccinia viruses.
We characterized the in vivo primary and secondary murine CD8+ T cell responses induced by immunization with influenza and vaccinia viruses, which were engineered to express the same H-2K(k)- and H-2K(d)-restricted epitopes. Our results show that the induction and magnitude of the primary CD8+ T cell response closely depends on the viral dose used for immunization, while it is not affected by the route of immunization. The induction of secondary CD8+ T cell responses appears to be highly restricted, as suggested by the lack of in vivo expansion of antigen-specific CD8+ T cells after repeated immunization with the same virus. In contrast, a 20- to 30-fold increase in the frequency of antigen-specific CD8+ T cells could be induced after combined immunization with recombinant influenza and vaccinia viruses. These findings may provide the basis for the development of new prophylactic and therapeutic strategies to prevent or control intracellular infections and certain malignancies.
Animals↗
Quantification of antigen specific CD8+ T cells using an ELISPOT assay.
An ELISPOT assay to detect and determine the number of antigen specific CD8+ T cells was standardized using cloned murine CD8+ T cells specific for the epitope SYVPSAEQI of a rodent malaria antigen. This assay is based on the detection of IFN-gamma secretion by single cells after their stimulation with antigen. The interferon secretion is visualized as spots revealed by using enzyme labeled anti-IFN-gamma monoclonal antibodies. Using known numbers of cloned murine CD8+ T cells it was determined that the assay detects 80-95% of these CD8+ T cells. The optimal culture conditions for the stimulation of the CD8+ T cells were determined and the antigen concentration, number of antigen presenting cells and supplement of growth factors required to perform the assay were defined. This ELISPOT assay can be performed with spleen cells from immunized mice, and provide the precise number of antigen specific CD8+ T cells present in mixed lymphocyte populations. This method is more sensitive than the chromium-51 release assay, and much simpler than the conventional precursor frequency analysis, providing the number of antigen specific CD8+ T cells in 36-48 h.
Amino Acid Sequence↗
Expression of histone H1 (zero) in transcriptionally activated supraoptic neurons.
This study has analysed by immunocytochemistry the expression pattern of histone H1 zero after the osmotically induced activation of transcription in supraoptic nucleus neurons of the rat. In control rats, histone H1 zero was constitutively expressed in neuronal and glial cell nuclei of supraoptic nucleus. After chronic neuronal stimulation by intermittent salt-loading, the majority of neuronal cell nuclei exhibited a marked reduction of immunostaining, which was confirmed by densitometric analysis of immunoreactivity. This effect was reversible, since optical density values returned to control levels when the stimulation of supraoptic neurons was suppressed by rehydration. Ultrastructural immunocytochemistry of histone H1 zero showed that immunogold particles specifically decorated chromatin fibers, with the highest accumulation of particles being on the condensed inactive chromatin. These results indicate that transcriptional activation in supraoptic neurons is accompanied by a depletion of the chromatin-associated histone H1 zero, and also suggest that this transcription-dependent expression of histone H1 zero may be involved in regulating chromatin condensation and gene expression in mature neurons that constitutively express this protein.
Animals↗
Enhanced proteolytic processing of the human immunodeficiency virus type 1 envelope protein in murine Ltk(-) cells.
Proteolytic processing of the human immunodeficiency virus type 1 (HIV-1) envelope (Env) precursor glycoprotein (gp160) to produce the mature gp120 and gp41 proteins is required for virus infection and virus-induced cell fusion. It has also been suggested that cleavage of gp120 at the immunodominant V3 loop region is required for virus-to-cell and cell-to-cell fusion. In this investigation we have studied the proteolytic processing of the HIV-1 Env in cells of various origins (human, monkey, and mouse) infected with a vaccinia virus recombinant expressing the entire gp160 protein (VV-env-1). We have observed that in murine Ltk(-) cells, in addition to the proteolytic cleavage of gp160 at the gp120/gp41 site, there is also extensive intracellular proteolytic processing of gp160 at the V3 loop and at a novel site located at the C terminus of gp41. Similar proteolytic processing of the Env precursor was observed after treatment of extracts of VV-env-1-infected monkey cells with thrombin, a trypsin-like protease that has been shown to cleave the gp120 at the V3 loop. Our findings suggest that murine Ltk(-) cells could be a good model system for structural studies of Env with different HIV isolates and in searches for proteinase inhibitors that could prevent HIV-1 infection of susceptible cells by blocking proteolysis of Env.
Animals↗