Methodological reappraisal of platelet radiolabelling with 111indium.
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Blood Platelet Disorders↗
Biomedical subjects
M Rodrigues
Publications and source records attributed to M Rodrigues.
Clear-cell sarcoma of tendons and aponeuroses studied by immunoscintigraphy.
Clear-cell sarcoma is a rare tumor that arises in association with tendons and aponeuroses. Although it shares with malignant melanoma several histologic and ultrastructural features, it has a clinical course different from that of conventional melanomas. A case of clear-cell sarcoma studied by immunoscintigraphy with 99mTc-labeled F(ab')2 fragments of the monoclonal antibody 225.28 S is reported.
Adenocarcinoma, Clear Cell↗
[Detection, evaluation and care of pain. The nurse's role].
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Analgesics↗
PGE0 inhibits collagen and glycosaminoglycan-synthesis in the rabbit arterial wall.
The influence of 13,14-dihydro-PGE1 (PGE0), a biologically active metabolite of PGE1, on collagen and glycosaminoglycan synthesis by the rabbit arterial wall was assessed and compared with the effect of PGE1. Collagen (COL) and glycosaminoglycan (GAG) synthesis was measured using 14C proline- and 35S-incorporation respectively and both were subsequently quantified by autoradiography. PGE1 decreased GAG-synthesis by 40%, while PGE0 caused a 25% decrease. COL-synthesis after PGE1 treatment was diminished by 35%, while the biologically active metabolite caused a drop of 30%. Five and 15 micrograms/kg doses of both compounds were almost equally effective, 1 microgram was without effect. These findings indicate that PGE0 shares the inhibitory effect of PGE1 on COL and GAG biosynthesis. This metabolite has about 60 to 70% of the biological activity of its parent compound PGE1. These results suggest that part of the effects of PGE1 in inhibiting extracellular matrix production could be due to its metabolite PGE0.
Alprostadil↗
[The treatment of obstructive hypertrophic myocardiopathy refractory to medical therapy].
Until a few years ago, therapy of refractory Hypertrophic Obstructive cardiomyopathy was mainly surgical--Morrow's myotomy/myectomy or mitral valve replacement. Despite the good results of these techniques, they are not free of mortality and morbidity. In the last years a new and promising therapy has been developed: the Dual Chamber Pacemaker. Technically easier and less invasive than surgery, this therapy has achieved better results and lower mortality and morbidity during the follow-up.
Cardiomyopathy, Hypertrophic↗
Biochemistry and molecular biology of the main diagnostic antigen of Paracoccidioides brasiliensis.
The 43,000 dalton glycoprotein of Paracoccidioides brasiliensis (gp 43) is the main exocellular antigen recognized by sera from patients with paracoccidioidomycosis in a variety of serological assays. Specific conformational peptide epitopes are recognized by the human antibodies as determined by antigen deglycosylation. Procedures for the purification of the gp43 using immunoaffinity chromatography have been described. The secretion of the gp43 as a function of the growth curve, its partial aggregation with a proteolytic enzyme, ability to bind laminin, as well as to form circulating immunocomplexes in vivo could play a role in pathogenesis. Crude antigenic preparations depleted of gp43 epitopes lost their ability to elicit positive skin tests. Accordingly, the purified gp43 molecule induced delayed hypersensitivity reactions in man and infected animals, caused a T-CD4-dependent proliferation of lymph node cells from mice immunized with it, and of peripheral blood lymphocytes from an individual sensitized to P. brasiliensis by prolonged contact with the fungus. To identify the immunodominant epitopes in both humoral and cellular reactions, the gp43 gene has been cloned, sequenced, and partly expressed. It bears peptide sequences homologous to those of beta-1,3-glucanases from Candida albicans and Saccharomyces cerevisiae but has no enzymatic activity itself. The molecular weight of the unglycosylated antigen is 42,227. A single N-linked oligosaccharide chain in the gp43 contains alpha-D-mannopyranosyl, beta-D-galactofuranosyl and N-acetylglucosaminyl units with the predominant ratio of 10:2:2, and characteristics of a high mannose type.
Amino Acid Sequence↗
The effect of NO/EDRF and monocytes/macrophages on LDL-oxidation.
Beside prostaglandin (PG) I2 and tissue plasminogen activator (tPA), nitric oxide (NO) is a key fepellant substance contributing to haemostatic balancing. The role of low-density lipoproteins (LDL) in the pathogenesis of atherosclerosis has been gaining increasing importance. It is well accepted that LDL in their modified (i.e. oxidized) form are no longer recognized by the LDL-receptor, but are taken up by cells of the arterial wall, especially macrophages, in a non-regulated manner through the so called scavenger-receptor pathway. This process leads to the formation of foam cells, the hallmark of the atherosclerotic lesion. NO is also produced in relevant amounts by macrophages. The interaction of NO and LDL with macrophages is thus of key importance in the onset of early lesions. While oxidized LDL (oxLDL) are resulting in a decreased NO availability, NO seems to prevent LDL-oxidation. In contrast, however, in the presence of superoxides oxidation may result. All these potential actions have to be discussed in view of the extremely short half-life of NO indicating that these actions are restricted most likely to the local site of biosynthesis being dependent on the actual concentration, the duration of availability and the presence of transition metals. These findings indicate that NO may play a dual pro- and antiatherosclerotic role being dependent on local factors only.
Animals↗
Platelet labeling--methodology and clinical applications.
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Blood Platelets↗
Influenza and vaccinia viruses expressing malaria CD8+ T and B cell epitopes. Comparison of their immunogenicity and capacity to induce protective immunity.
We compared the effectiveness of several recombinant influenza and vaccinia viruses to induce a malaria-specific immune response. The CD8+ T cell epitope of the circumsporozoite (CS) protein of Plasmodium yoelii, a rodent malaria parasite, was expressed in two distinct influenza virus proteins, the hemagglutinin and the neuraminidase. These recombinant viruses were found to be equally efficient at inducing CS-specific CD8+ T cells in mice. A third recombinant virus, which expresses a B cell epitope of the CS protein, induced neutralizing anti-sporozoite Abs. Expression in the same recombinant virus of the CD8+ T cell epitope and of the B cell epitope did not impair the capacity of this recombinant virus to induce malaria-specific CD8+ T cells and neutralizing Abs. The immunogenicity of a vaccinia virus, expressing the entire CS protein, was compared with that of a highly attenuated vaccinia strain expressing the same protein and with that of another vaccinia virus expressing only the CD8+ T cell epitope. All three vaccinia virus recombinants elicited CS-specific CD8+ cells and a potent inhibitory response against pre-erythrocytic stages of malaria parasites. Optimal levels of anti-sporozoite Abs, inhibition of liver stage development, and protection against malaria infection resulted from repeatedly immunizing the animals with recombinant influenza viruses followed by boosters with a recombinant vaccinia virus. These findings support the concept that live viral vectors expressing the appropriate proteins and/or epitopes can be used as promising vaccine candidates.
Amino Acid Sequence↗
Endogenous Fusarium endophthalmitis in a patient with acute lymphocytic leukemia.
Endogenous fungal endophalmitis is an uncommon complication of systemic mycosis. Only a few cases involving Fusarium have been reported, most with unfavorable visual outcomes. We examined a 31-year-old woman with acute lymphocytic leukemia who developed sudden visual loss in her right eye. A dense, white placoid infiltrate was present in the right macula extending into the vitreous. An iris nodule and hypopyon were present in the left eye. A vitreous aspirate of the right eye was positive for Fusarium species. The patient progressively lost vision despite amphotericin B and 5-fluorocytosine therapy. She died from bronchopneumonia, fungemia, and multisystem failure. Histopathologic study disclosed a panophthalmitis with Fusarium organisms invading all the ocular coats in the right eye. Leukemic infiltrates were present in the left iris, anterior chamber, and trabecular meshwork. The ocular destructiveness of Fusarium may be caused by marked mycotic vascular invasion and occlusion with consequent infarction and necrosis of ocular tissues.
Adult↗
Synergistic antiplatelet action of nitric oxide (NO) with PGD2 and its metabolite PGJ2--relevance for cerebral circulation?
The PGI2/NO axis is well accepted for its central regulatory role in maintaining haemostatic balance in large arteries. Earlier findings suggest that PGD2 may also play a role in haemostatic regulation of human cerebral circulation. We therefore wondered whether PGD2 and its metabolite PGJ2 synergise in-vitro with NO. We approached this question using platelets of ten healthy donors and ADP as aggregation-inducing stimulus. Both PGD2 and PGJ2 do inhibit ADP-induced platelet aggregation in a dose-dependent manner. Platelet aggregation findings demonstrate that PGD2 and NO synergise, as does the metabolite PGJ2. Our data are indicative that the PGD2/NO and, in less extent, PGJ2/NO synergism might be of special importance for the cerebrovascular haemostatic control.
Adenosine Diphosphate↗
[Instruments in nuclear cardiology].
The instrumentation required for performing nuclear cardiology can be schematically separated in three classes: 1) The usual material of nuclear medicine necessary for the reception, maintenance, preparation, administration and elimination of radionuclides and radiopharmaceuticals, 2) The instruments necessary for the detection of radiations and for the register and analysis of data, 3) The cardiologic material required for performing the stress and for monitoring coronary patients. There are well defined and sinalized areas. In the daily routine, protection of radiations and quality control of the radiopharmaceuticals and the equipment are fundamental. Gamma camera is the most used detector. Collimators and computers are other equipments essential for performing scintigraphy.
Cardiology↗
Priming with recombinant influenza virus followed by administration of recombinant vaccinia virus induces CD8+ T-cell-mediated protective immunity against malaria.
Live vectors expressing foreign antigens have been used to induce immunity against several pathogens. However, for the virulent rodent malaria parasite Plasmodium yoelii, the use of recombinant vaccinia virus, pseudorabies virus, or Salmonella, expressing the circumsporozoite protein of this parasite, failed to induce protection. We generated a recombinant influenza virus expressing an epitope from the circumsporozoite protein of P. yoelii known to be recognized by CD8+ T cells and demonstrated that this vector induced class I major histocompatibility complex-restricted cytotoxic T cells against this foreign epitope. Immunization of mice with this recombinant influenza virus, followed by a recombinant vaccinia virus expressing the entire circumsporozoite protein, induced protective immunity against sporozoite-induced malaria. The sequence of immunization appears to be crucial, since a primer injection with recombinant vaccinia virus, followed by a booster injection with recombinant influenza virus, failed to induce protection. The protection induced by immunization with these recombinant viruses is mostly mediated by CD8+ T cells, as treatment of mice with anti-CD8 monoclonal antibody abolishes the anti-malarial immunity. The use of different live vectors for primer and booster injections has a synergistic effect on the immune response and might represent an effective general strategy for eliciting protective immune responses to key antigens of microbial pathogens.
Amino Acid Sequence↗
99Tcm-HMPAO brain SPECT in the evaluation of prognosis after surgical resection of astrocytoma. Comparison with other noninvasive imaging techniques (CT, MRI and 201Tl SPECT).
High-grade astrocytoma represents the most common primary malignant brain tumour in the adult, and is associated with high morbidity and mortality rates. The aim of this study was to investigate the prognostic value of 99Tcm-hexamethylpropyleneamine oxime (HMPAO) brain single photon emission computed tomography (SPECT) in predicting neurological function and tumour therapy response after surgical resection of astrocytoma. The correlation between 99Tcm-HMPAO studies and other noninvasive methods [computed tomography (CT), magnetic resonance imaging (MRI) and 201Tl (SPECT)] was evaluated. The clinical population included 21 patients with previous surgical debulking of astrocytoma. All patients were evaluated with 99Tcm-HMPAO brain SPECT. Seven patients, who suffered progressive clinical deterioration after radiotherapy, underwent dual-isotope SPECT imaging with 201Tl and 99Tcm-HMPAO. Neurological examinations and CT were performed in all patients. Magnetic resonance imaging was performed in seven patients. Prior to radiotherapy and/or chemotherapy, the patients with neurological improvement during the follow-up evaluation commonly showed less intense abnormal 99Tcm-HMPAO uptake than the patients without neurological improvement. In addition, after therapy none of the former patients had increased 99Tcm-HMPAO uptake. Most patients without neurological improvement had evidence of high focal uptake. Computed tomography and MRI usually demonstrated pathological contrast enhancement regardless of the presence or absence of improvement of neurological function. Foci of high 201Tl accumulation were observed on SPECT images in five patients. In four of these patients, the 99Tcm-HMPAO was greater than in normal brain, and in two patients the 99Tcm-HMPAO uptake was lower than in normal brain. One patient with decreased 99Tcm-HMPAO uptake in a medium-sized lesion had a normal 201Tl study. Our hypothesis that 99Tcm-HMPAO SPECT may be useful for providing prognostic information after surgical debulking of astrocytoma seems to be promising. Further studies are needed to document this new important role of 99Tcm-HMPAO SPECT.
Adolescent↗
Modulation of retinoblastoma cell characteristics by hexamethylene bis-acetamide and other differentiating agents in culture.
The undifferentiated Y-79 retinoblastoma cell line can be induced by specific agents to express characteristics of mature retinal cells. In the present study, attached Y-79 cell cultures were treated with hexamethylene bis-acetamide (HMBA) and other differentiating agents and examined for "neuronal" and other properties. Immunocytochemical staining was performed with antibodies against neuron- and retina-specific antigens, [synaptophysin, interphotoreceptor retinoid-binding protein (IRBP), neural cell adhesion molecule (N-CAM), and rod- and cone-specific transducin (TR alpha and TC alpha)] and microtubule-associated protein (MAP-1) and tubulin. Enhanced expression of tubulin was observed with cAMP treatment in FBS media. Expression of N-CAM was observed in all groups. Morphological differentiation was pronounced with HMBA and butyrate treatment, with HMBA inducing increased tubulin expression after 2 weeks of treatment. Expression of TR alpha was minimal under all culture conditions, whereas TC alpha was ubiquitously expressed. This supports the concept that Y-79 retinoblastoma is predominantly of cone neuronal origin and that, surprisingly, immunocytochemical differentiation is not correlated with the marked morphological changes induced by the major differentiating agents used.
Acetamides↗
The relative contribution of antibodies, CD4+ and CD8+ T cells to sporozoite-induced protection against malaria.
Protective immunity against Plasmodium yoelii, induced by sporozoite immunization, was investigated using a quantitative method based on the measurement of plasmodial ribosomal RNA in the liver of sporozoite-challenged mice. The relative importance of the different immune mechanisms induced by sporozoite immunization was determined by evaluating quantitatively the anti-parasite activity of antibodies, CD4+ and CD8+ T cells. The role of antibodies was determined by passive transfer of immune sera to naive mice. The transfer to mice of sera obtained after a single immunizing dose reduced the liver stages by 47%. The respective contribution of CD4+ and CD8+ T-cell subsets was determined in B10 (H-2b) mice, treated with a monoclonal antibody (mAb) which inhibits B-cell maturation, and subsequently immunized once with irradiated sporozoites. These mice produced low levels of anti-sporozoite antibodies, but were capable of inhibiting the development of liver stages as efficiently as non-manipulated immunized mice. Administration of either anti-CD4 or anti-CD8 mAb to these mice, did not significantly decrease their capacity to inhibit the development of liver stages. We only observed a significant loss of immunity when the mice were depleted in vivo of both CD4+ and CD8+ T cells. In contrast to earlier studies, we found that the induction of protective immunity is not a phenomenon restricted to a few strains of mice having a particular genetic make-up. The apparent non-responsiveness observed in some strains of mice can be overcome by using larger immunizing doses.
Animals↗
Immunoscintigraphy with 99mTc-labelled anti-CEA monoclonal antibody in colorectal carcinoma.
With the introduction of immunoscintigraphy (IS) with 99mTc-labelled anti-CEA monoclonal antibodies (MoAb), a clinical relevant method in nuclear medicine can be expected in the diagnosis and follow up of colorectal cancers. We performed IS (whole body, planar and SPECT) with a 99mTc-labelled intact anti-CEA MoAb (BW 431/26) in 18 patients with primary colorectal carcinoma, metastases or suspicious recurrences from colorectal carcinoma. The results of anti-CEA IS, serum CEA and Ca 19-9 levels were evaluated. Immunoscintigraphy yielded an overall sensitivity of 70.0%, 37.5% for primary tumors, 75.0% for recurrences and 100% for distant metastases. Serum CEA levels were elevated in 10 out of 18 patients (sensitivity 55.5%) and Ca 19-9 were elevated in eight out of 18 patients (sensitivity 44.4%). In the group of patients with metastases, CEA had a sensitivity of 100% and Ca 19-9, of 83.3%. From this prospective study, we can conclude that IS with 99mTC-BW 431/26 is a reliable tool in the post-operative follow-up study of patients with colorectal carcinoma, namely in the detection of distant metastases.
Aged↗
Clinical and histopathologic changes in the host cornea after epikeratoplasty for keratoconus.
Five consecutive patients underwent epikeratoplasty for keratoconus. Postoperatively, four patients had poor visual acuity (average, 20/200) secondary to folds in Descemet's membrane and interface scarring. Two underwent penetrating keratoplasty eight months later. Histopathologic examination of the host corneas and the overlying lenticules disclosed epithelial irregularity and subepithelial fibrosis. The host corneas showed folds in Descemet's membrane and focal posterior stromal fibrosis. Electron microscopy disclosed breaks in Bowman's membrane with irregular collagen, posterior aggregates of amorphous material, and focal endothelial degeneration. The fifth patient had graft ulceration and vascularization that required removal of the lenticule. She underwent a penetrating keratoplasty five months later and histopathologic examination demonstrated persistent folds in Descemet's membrane. Immunostaining of specimens from three cases disclosed a reduced expression of sulfated epitopes of keratan sulfate and an increase in sulfated dermatan sulfate in the lenticule and host corneal tissues. These alterations in stromal proteoglycans are characteristic of stromal scars and keratoconus and provide evidence of pathologic processes in the graft tissue. Because of potential complications, epikeratoplasty should be considered only for those patients who are unsuitable candidates for contact lenses or penetrating keratoplasty.
Adult↗